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Sample records for myc-mediated hypertrophic cardiomyopathy

  1. [Hypertrophic cardiomyopathy. Arrhythmia in hypertrophic cardiomyopathy].

    PubMed

    Colín Lizalde, Luis de Jesús

    2003-01-01

    Hypertrophic cardiomyopathy is a relatively common genetic disorder with heterogeneity in mutations, forms of presentation, prognosis and treatment strategies. Hypertrophic cardiomyopathy is recognized as the most common cause of sudden cardiac death that occurs in young people, including athletes. The clinical diagnosis is complemented with the ecocardiographic study, in which an abnormal myocardial hypertrophy of the septum can be observed in the absence of a cardiac or systemic disease (arterial systemic hypertension, aortic stenosis). The annual sudden mortality rate is 1% and, in selected populations, it ranges between 3 and 6%. The therapeutic strategies depend on the different subsets of patients according to the morbidity and mortality, sudden cardiac death, obstructive symptoms, heart failure or atrial fibrillation and stroke. High risk patients for sudden death may effectively be treated with the automatic implantable cardioverter-defibrillator.

  2. Hypertrophic cardiomyopathy in Friedreich's ataxia.

    PubMed

    Fayssoil, A; Nardi, O; Orlikowski, D; Annane, D

    2008-07-21

    Friedreich's ataxia is an autosomal recessive disorder characterized by spinocerebellar degeneration. It is caused by a mutation that consists of an unstable expansion of GAA repeats in the first intron of the gene encoding frataxin on chromosome 9 (9q13). We reported a case of hypertrophic cardiomyopathy associated with Friedreich's ataxia in a twenty year old patient.

  3. Genetics of hypertrophic and dilated cardiomyopathy.

    PubMed

    Friedrich, Felix W; Carrier, Lucie

    2012-10-01

    Cardiomyopathies are categorized as extrinsic, being caused by external factors, such as hypertension, ischemia, inflammation, valvular dysfunction, or as intrinsic, which correspond to myocardial diseases without identifiable external causes. These so called primary cardiomyopathies can be categorized in four main forms: hypertrophic, dilated, restrictive, and arrhythmogenic right ventricular cardiomyopathy. Cardiomyopathies are diagnosed by clinical expression, echocardiography, electrocardiography, non-invasive imaging, and sometimes by cardiac catheterization to rule out external causes as ischemia. The two main forms of primary cardiomyopathies are the hypertrophic and dilated cardiomyopathies. Most of hypertrophic cardiomyopathy and 20-50% of dilated cardiomyopathy are familial showing a wide genetic and phenotypic heterogeneity. This review presents the current knowledge on the causative genes, molecular mechanisms and the genotype � phenotype relations of hypertrophic and dilated cardiomyopathies.

  4. [The origin of hypertrophic cardiomyopathy].

    PubMed

    Moiseev, V S

    1985-01-01

    The author describes the clinical cases of hypertrophic cardiomyopathy (CMP). The development of obstructive CMP in a patient with hyperparathyroidism indicates a possible pathogenetic role of endocrine factors and calcium metabolism abnormalities. The familial character of the disease and its combination with hereditary diseases (familial microspherocytosis) point to the significance of genetic factors. In addition, marked hypertrophy of the myocardium (without dilatation) including hypertrophy with obstruction of the outflow tract of the left ventricle was observed in nonspecific protracted myocarditis, alcoholic injury to the heart, in athletes, in coronary heart disease (after survival of myocardial infarction). It is suggested that hypertrophic CMP (similarly to restrictive and congestive CMP) is most likely a syndrome of varying origin.

  5. Hypertrophic cardiomyopathy: the early years.

    PubMed

    Braunwald, Eugene

    2009-12-01

    Hypertrophic obstructive cardiomyopathy (HOCM) has four major features: (1) severe left ventricular hypertrophy, often most prominent in the basal interventricular septum; (2) frequent familial occurrence with autosomal dominant transmission; (3) occurrence of sudden cardiac death that is usually considered to be due to ventricular fibrillation; and (4) presence of hemodynamic evidence of labile intraventricular obstruction. The key papers describing the recognition of each of these features, as well as of various combinations of them, are reviewed in this paper. Particular attention is focused on the very frequent finding of marked lability of intraventricular obstruction. The recognition of this fourth and last major feature in 1959 makes 2009 the golden anniversary year marking completion of the description of the major features of HOCM.

  6. Hypertrophic Cardiomyopathy in Athletes: Catching a Killer.

    ERIC Educational Resources Information Center

    Maron, Barry J.

    1993-01-01

    A leading cause of sudden death among young athletes, hypertrophic cardiomyopathy (HCM) does not always present cardiac signs and symptoms. Echocardiography offers the most effective means for diagnosis. Some patients require pharmaceutical or surgical intervention. Patients with HCM should not engage in organized competitive sports or…

  7. Infective endocarditis in hypertrophic cardiomyopathy

    PubMed Central

    Dominguez, Fernando; Ramos, Antonio; Bouza, Emilio; Muñoz, Patricia; Valerio, Maricela C.; Fariñas, M. Carmen; de Berrazueta, José Ramón; Zarauza, Jesús; Pericás Pulido, Juan Manuel; Paré, Juan Carlos; de Alarcón, Arístides; Sousa, Dolores; Rodriguez Bailón, Isabel; Montejo-Baranda, Miguel; Noureddine, Mariam; García Vázquez, Elisa; Garcia-Pavia, Pablo

    2016-01-01

    Abstract Infective endocarditis (IE) complicating hypertrophic cardiomyopathy (HCM) is a poorly known entity. Although current guidelines do not recommend IE antibiotic prophylaxis (IEAP) in HCM, controversy remains. This study sought to describe the clinical course of a large series of IE HCM and to compare IE in HCM patients with IE patients with and without an indication for IEAP. Data from the GAMES IE registry involving 27 Spanish hospitals were analyzed. From January 2008 to December 2013, 2000 consecutive IE patients were prospectively included in the registry. Eleven IE HCM additional cases from before 2008 were also studied. Clinical, microbiological, and echocardiographic characteristics were analyzed in IE HCM patients (n = 34) and in IE HCM reported in literature (n = 84). Patients with nondevice IE (n = 1807) were classified into 3 groups: group 1, HCM with native-valve IE (n = 26); group 2, patients with IEAP indication (n = 696); group 3, patients with no IEAP indication (n = 1085). IE episode and 1-year follow-up data were gathered. One-year mortality in IE HCM was 42% in our study and 22% in the literature. IE was more frequent, although not exclusive, in obstructive HCM (59% and 74%, respectively). Group 1 exhibited more IE predisposing factors than groups 2 and 3 (62% vs 40% vs 50%, P < 0.01), and more previous dental procedures (23% vs 6% vs 8%, P < 0.01). Furthermore, Group 1 experienced a higher incidence of Streptococcus infections than Group 2 (39% vs 22%, P < 0.01) and similar to Group 3 (39% vs 30%, P = 0.34). Overall mortality was similar among groups (42% vs 36% vs 35%, P = 0.64). IE occurs in HCM patients with and without obstruction. Mortality of IE HCM is high but similar to patients with and without IEAP indication. Predisposing factors, previous dental procedures, and streptococcal infection are higher in IE HCM, suggesting that HCM patients could benefit from IEAP. PMID:27368014

  8. Aortic biomechanics in hypertrophic cardiomyopathy

    PubMed Central

    Badran, Hala Mahfouz; Soltan, Ghada; Faheem, Nagla; Elnoamany, Mohamed Fahmy; Tawfik, Mohamed; Yacoub, Magdi

    2015-01-01

    Background: Ventricular-vascular coupling is an important phenomenon in many cardiovascular diseases. The association between aortic mechanical dysfunction and left ventricular (LV) dysfunction is well characterized in many disease entities, but no data are available on how these changes are related in hypertrophic cardiomyopathy (HCM). Aim of the work: This study examined whether HCM alone is associated with an impaired aortic mechanical function in patients without cardiovascular risk factors and the relation of these changes, if any, to LV deformation and cardiac phenotype. Methods: 141 patients with HCM were recruited and compared to 66 age- and sex-matched healthy subjects as control group. Pulse pressure, aortic strain, stiffness and distensibility were calculated from the aortic diameters measured by M-mode echocardiography and blood pressure obtained by sphygmomanometer. Aortic wall systolic and diastolic velocities were measured using pulsed wave Doppler tissue imaging (DTI). Cardiac assessment included geometric parameters and myocardial deformation (strain and strain rate) and mechanical dyssynchrony. Results: The pulsatile change in the aortic diameter, distensibility and aortic wall systolic velocity (AWS') were significantly decreased and aortic stiffness index was increased in HCM compared to control (P < .001) In HCM AWS' was inversely correlated to age(r = − .32, P < .0001), MWT (r = − .22, P < .008), LVMI (r = − .20, P < .02), E/Ea (r = − .16, P < .03) LVOT gradient (r = − 19, P < .02) and severity of mitral regurg (r = − .18, P < .03) but not to the concealed LV deformation abnormalities or mechanical dyssynchrony. On multivariate analysis, the key determinant of aortic stiffness was LV mass index and LVOT obstruction while the role LV dysfunction in aortic stiffness is not evident in this population. Conclusion: HCM is associated with abnormal aortic mechanical properties. The severity of cardiac

  9. An unusual ST-segment elevation: apical hypertrophic cardiomyopathy shows the ace up its sleeve.

    PubMed

    de Santis, Francesco; Pergolini, Amedeo; Zampi, Giordano; Pero, Gaetano; Pino, Paolo Giuseppe; Minardi, Giovanni

    2013-01-01

    Apical hypertrophic cardiomyopathy is part of the broad clinical and morphologic spectrum of hypertrophic cardiomyopathy. We report a patient with electrocardiographic abnormalities in whom acute coronary syndrome was excluded and apical hypertrophic cardiomyopathy was demonstrated by careful differential diagnosis.

  10. Posterolateral hypertrophic cardiomyopathy: a rare, but clinically significant variant of hypertrophic cardiomyopathy.

    PubMed

    Seki, Atsuko; Perens, Gregory; Fishbein, Michael C

    2014-01-01

    Posterolateral hypertrophic cardiomyopathy (HCM) is a rare variant of HCM. Segmental HCM is seen in 12% of cases of HCM. Among the patterns of segmental HCM, posterolateral HCM is the least common type. Our case of an 18-year old male documents this unusual type of cardiomyopathy. In this form of HCM, left ventricular thickness and the extent of hypertrophy might be underestimated by 2-dimensional echocardiography. This case illustrates the echocardiographic and pathologic features of posterolateral HCM.

  11. Hypertrophic Cardiomyopathy in Owl Monkeys (Aotus spp.)

    PubMed Central

    Knowlen, Grant G; Weller, Richard E; Perry, Ruby L; Baer, Janet F; Gozalo, Alfonso S

    2013-01-01

    Cardiac hypertrophy is a common postmortem finding in owl monkeys. In most cases the animals do not exhibit clinical signs until the disease is advanced, making antemortem diagnosis of subclinical disease difficult and treatment unrewarding. We obtained echocardiograms, electrocardiograms, and thoracic radiographs from members of a colony of owl monkeys that previously was identified as showing a 40% incidence of gross myocardial hypertrophy at necropsy, to assess the usefulness of these modalities for antemortem diagnosis. No single modality was sufficiently sensitive and specific to detect all monkeys with cardiac hypertrophy. Electrocardiography was the least sensitive method for detecting owl monkeys with hypertrophic cardiomyopathy. Thoracic radiographs were more sensitive than was electrocardiography in this context but cannot detect animals with concentric hypertrophy without an enlarged cardiac silhouette. Echocardiography was the most sensitive method for identifying cardiac hypertrophy in owl monkeys. The most useful parameters suggestive of left ventricular hypertrophy in our owl monkeys were an increased average left ventricular wall thickness to chamber radius ratio and an increased calculated left ventricular myocardial mass. Parameters suggestive of dilative cardiomyopathy were an increased average left ventricular myocardial mass and a decreased average ratio of left ventricular free wall thickness to left ventricular chamber radius. When all 4 noninvasive diagnostic modalities (physical examination, echocardiography, electrocardiography, and thoracic radiography) were used concurrently, the probability of detecting hypertrophic cardiomyopathy in owl monkeys was increased greatly. PMID:23759531

  12. Hypertrophic cardiomyopathy in owl monkeys (Aotus spp.).

    PubMed

    Knowlen, Grant G; Weller, Richard E; Perry, Ruby L; Baer, Janet F; Gozalo, Alfonso S

    2013-06-01

    Cardiac hypertrophy is a common postmortem finding in owl monkeys. In most cases the animals do not exhibit clinical signs until the disease is advanced, making antemortem diagnosis of subclinical disease difficult and treatment unrewarding. We obtained echocardiograms, electrocardiograms, and thoracic radiographs from members of a colony of owl monkeys that previously was identified as showing a 40% incidence of gross myocardial hypertrophy at necropsy, to assess the usefulness of these modalities for antemortem diagnosis. No single modality was sufficiently sensitive and specific to detect all monkeys with cardiac hypertrophy. Electrocardiography was the least sensitive method for detecting owl monkeys with hypertrophic cardiomyopathy. Thoracic radiographs were more sensitive than was electrocardiography in this context but cannot detect animals with concentric hypertrophy without an enlarged cardiac silhouette. Echocardiography was the most sensitive method for identifying cardiac hypertrophy in owl monkeys. The most useful parameters suggestive of left ventricular hypertrophy in our owl monkeys were an increased average left ventricular wall thickness to chamber radius ratio and an increased calculated left ventricular myocardial mass. Parameters suggestive of dilative cardiomyopathy were an increased average left ventricular myocardial mass and a decreased average ratio of left ventricular free wall thickness to left ventricular chamber radius. When all 4 noninvasive diagnostic modalities (physical examination, echocardiography, electrocardiography, and thoracic radiography) were used concurrently, the probability of detecting hypertrophic cardiomyopathy in owl monkeys was increased greatly.

  13. Diagnosis and management of hypertrophic cardiomyopathy

    PubMed Central

    Vischer, Annina S; Perez-Tome, Maria Carrillo; Castelletti, Silvia

    2015-01-01

    The clinical spectrum of hypertrophic cardiomyopathy (HCM) is complex and includes a variety of phenotypes, which leads to different types of manifestations. Although most of the patients are asymptomatic, a significant proportion of them will develop symptoms or risk of arrhythmias and sudden cardiac death (SCD). Therefore, the objectives of HCM diagnosis and management are to relieve the patients' symptoms (chest pain, heart failure, syncope, palpitations, etc.), prevent disease progression and major cardiovascular complications and SCD. The heterogeneity of HCM patterns, their symptoms and assessment is a challenge for the cardiologist. PMID:26693331

  14. Screening for hypertrophic cardiomyopathy in cats.

    PubMed

    Häggström, Jens; Luis Fuentes, Virginia; Wess, Gerhard

    2015-12-01

    Hypertrophic cardiomyopathy (HCM) is the most common heart disease in cats, and it can lead to increased morbidity and mortality. Cats are often screened for HCM because of the presence of a heart murmur, but screening for breeding purposes has also become common. These cats are usually purebred cats of breeding age, and generally do not present with severe disease or with any clinical signs. This type of screening is particularly challenging because mild disease may be difficult to differentiate from a normal phenotype, and the margin for error is small, with potentially major consequences for the breeder. This article reviews HCM screening methods, with particular emphasis on echocardiography.

  15. Hypertrophic cardiomyopathy simulating an infiltrative myocardial disease.

    PubMed Central

    Frustaci, A; Loperfido, F; Pennestrì, F

    1985-01-01

    Congestive heart failure developed in a patient with low electrocardiographic QRS voltages, diffuse thickening of the septum and free cardiac wall, and a reduction in left ventricular internal diameter, which suggested an infiltrative heart muscle disease. Histological examination at necropsy showed hypertrophic cardiomyopathy with symmetrical left ventricular hypertrophy. Myocardial disarray of type 1A disorganisation was extensive and equally distributed in the ventricular septum and the left anterior and left posterior ventricular free walls. Severe fibrosis (40%) was also present and may have been a possible cause of the electrocardiographic abnormalities as well as of the lack of ventricular dilatation. Images PMID:4041302

  16. Myocardial Fibrosis as an Early Manifestation of Hypertrophic Cardiomyopathy

    PubMed Central

    Ho, Carolyn Y.; López, Begoña; Coelho-Filho, Otavio R.; Lakdawala, Neal K.; Cirino, Allison L.; Jarolim, Petr; Kwong, Raymond; González, Arantxa; Colan, Steven D.; Seidman, J.G.; Díez, Javier; Seidman, Christine E.

    2011-01-01

    BACKGROUND Myocardial fibrosis is a hallmark of hypertrophic cardiomyopathy and a proposed substrate for arrhythmias and heart failure. In animal models, profibrotic genetic pathways are activated early, before hypertrophic remodeling. Data showing early profibrotic responses to sarcomere-gene mutations in patients with hypertrophic cardiomyopathy are lacking. METHODS We used echocardiography, cardiac magnetic resonance imaging (MRI), and serum biomarkers of collagen metabolism, hemodynamic stress, and myocardial injury to evaluate subjects with hypertrophic cardiomyopathy and a confirmed genotype. RESULTS The study involved 38 subjects with pathogenic sarcomere mutations and overt hypertrophic cardiomyopathy, 39 subjects with mutations but no left ventricular hypertrophy, and 30 controls who did not have mutations. Levels of serum C-terminal propeptide of type I procollagen (PICP) were significantly higher in mutation carriers without left ventricular hypertrophy and in subjects with overt hypertrophic cardiomyopathy than in controls (31% and 69% higher, respectively; P<0.001). The ratio of PICP to C-terminal telopeptide of type I collagen was increased only in subjects with overt hypertrophic cardiomyopathy, suggesting that collagen synthesis exceeds degradation. Cardiac MRI studies showed late gadolinium enhancement, indicating myocardial fibrosis, in 71% of subjects with overt hypertrophic cardiomyopathy but in none of the mutation carriers without left ventricular hypertrophy. CONCLUSIONS Elevated levels of serum PICP indicated increased myocardial collagen synthesis in sarcomere-mutation carriers without overt disease. This profibrotic state preceded the development of left ventricular hypertrophy or fibrosis visible on MRI. (Funded by the National Institutes of Health and others.) PMID:20818890

  17. Septal Myectomy Surgery to Treat Obstructive Hypertrophic Cardiomyopathy (HCM)

    MedlinePlus

    Septal Myectomy Surgery to Treat Obstructive Hypertrophic Cardiomyopathy (HCM) Click Here to view the BroadcastMed, Inc. Privacy Policy and Legal Notice © 2017 BroadcastMed, Inc. All rights reserved.

  18. Cardiopulmonary Exercise Test in Hypertrophic Cardiomyopathy.

    PubMed

    Magri, Damiano; Santolamazza, Caterina

    2017-04-04

    Understanding the functional limitation in hypertrophic cardiomyopathy, the most common inherited heart disease, is challenging. Beside the occurrence of disease-related complications, several factors are potential determinants of exercise limitation, including left ventricular hypertrophy, myocardial fiber disarray, left ventricular outflow tract obstruction, microvascular ischemia, and interstitial fibrosis. Furthermore, drugs commonly used in the daily management of these patients may interfere with exercise capacity, especially those with a negative chronotropic effect. Cardiopulmonary exercise testing can safely and objectively evaluate the functional capacity of these patients and help the physician in understanding the mechanisms that underlie this limitation. Features that reduce exercise capacity may predict progression to heart failure in these patients and even the risk of sudden cardiac death.

  19. Two Cases of Apical Ballooning Syndrome Masking Apical Hypertrophic Cardiomyopathy

    PubMed Central

    Roy, Ranjini Raina; Hakim, Fayaz A.; Hurst, R. Todd; Simper, David; Appleton, Christopher P.

    2014-01-01

    Apical akinesis and dilation in the absence of obstructive coronary artery disease is a typical feature of stress-induced (takotsubo) cardiomyopathy, whereas apical hypertrophy is seen in apical-variant hypertrophic cardiomyopathy. We report the cases of 2 patients who presented with takotsubo cardiomyopathy and were subsequently found to have apical-variant hypertrophic cardiomyopathy, after the apical ballooning from the takotsubo cardiomyopathy had resolved. The first patient, a 43-year-old woman with a history of alcohol abuse, presented with shortness of breath, electrocardiographic and echocardiographic features consistent with takotsubo cardiomyopathy, and no significant coronary artery disease. An echocardiogram 2 weeks later revealed a normal left ventricular ejection fraction and newly apparent apical hypertrophy. The 2nd patient, a 70-year-old woman with pancreatitis, presented with chest pain, apical akinesis, and a left ventricular ejection fraction of 0.39, consistent with takotsubo cardiomyopathy. One month later, her left ventricular ejection fraction was normal; however, hypertrophy of the left ventricular apex was newly noted. To our knowledge, these are the first reported cases in which apical-variant hypertrophic cardiomyopathy was masked by apical ballooning from stress-induced cardiomyopathy. PMID:24808780

  20. Cardiac sarcoid: a chameleon masquerading as hypertrophic cardiomyopathy and dilated cardiomyopathy in the same patient.

    PubMed

    Agarwal, Anushree; Sulemanjee, Nasir Z; Cheema, Omar; Downey, Francis X; Tajik, A Jamil

    2014-05-01

    Sarcoidosis is a multisystem, granulomatous disease of unknown etiology often seen in young adults, with cardiac involvement in more than one-quarter of sarcoid patients. The clinical presentation of cardiac sarcoid depends upon the location and extent of myocardium involved. Although cardiac sarcoid may produce asymmetrical septal hypertrophy, it is most commonly considered in the differential diagnosis of dilated cardiomyopathy. The hypertrophic stage of cardiac sarcoid is rarely seen. We describe a case of cardiac sarcoid in a young patient wherein a distinctive appearance of the cardiac sarcoid spectrum from "hypertrophic" stage to thinned/scarred stage, masquerading as hypertrophic cardiomyopathy followed by dilated cardiomyopathy, is demonstrated.

  1. Cardiac norepinephrine kinetics in hypertrophic cardiomyopathy

    SciTech Connect

    Brush, J.E. Jr.; Eisenhofer, G.; Garty, M.; Stull, R.; Maron, B.J.; Cannon, R.O. III; Panza, J.A.; Epstein, S.E.; Goldstein, D.S.

    1989-04-01

    We examined the uptake and release of norepinephrine in the cardiac circulation and other regional vascular beds in 11 patients with hypertrophic cardiomyopathy (HCM) and in 10 control subjects during simultaneous infusion of tracer-labeled norepinephrine and isoproterenol. Cardiac neuronal uptake of norepinephrine was assessed by comparing regional removal of tracer-labeled norepinephrine with that of tracer-labeled isoproterenol (which is not a substrate for neuronal uptake) and by the relation between production of dihydroxyphenylglycol (DHPG), an exclusively intraneuronal metabolite of norepinephrine, and regional spillover of norepinephrine. Cardiac extraction of norepinephrine averaged 59 +/- 17% in the patients with HCM, significantly less than in the control subjects (79 +/- 13%, p less than 0.05), whereas cardiac extraction of isoproterenol was similar in the two groups (13 +/- 23% versus 13 +/- 14%), indicating that neuronal uptake of norepinephrine was decreased in the patients with HCM. The cardiac arteriovenous difference in norepinephrine was significantly larger in the patients with HCM than in the control subjects (73 +/- 77 versus 13 +/- 50 pg/ml, p less than 0.05), as was the product of the arteriovenous difference in norepinephrine and coronary blood flow (7.3 +/- 7.3 versus 0.8 +/- 3.0 ng/min, p less than 0.05).

  2. Potential applications for transesophageal echocardiography in hypertrophic cardiomyopathies.

    PubMed

    Widimsky, P; Ten Cate, F J; Vletter, W; van Herwerden, L

    1992-01-01

    The purpose of the present study was to evaluate the potential advantages of transesophageal echocardiography (TEE) in comparison with transthoracic echocardiography (TTE) in selected patients with hypertrophic cardiomyopathy. Ten patients with previously established or suspected diagnosis of hypertrophic cardiomyopathy were examined by TEE to solve specific clinical questions. TEE was well tolerated by all patients; no arrhythmias were seen during the procedure. The comparison of TTE and TEE showed the following: Advantages of TTE--better assessment of the left ventricle, myocardial thickness measurements available in all regions and sufficient for the diagnosis of hypertrophic cardiomyopathy in nine out of 10 patients; advantages of TEE--precise assessment of mitral valve morphology and regurgitant jets, detailed evaluation of systolic anterior motion, and subaortic membrane (not seen by TTE) recognized in one patient. Clinically, in three patients TEE influenced the management (mitral leaflet perforation, subaortic membrane, and residual mitral regurgitation after valvuloplasty). Thus TEE enables more precise diagnosis in some patients with hypertrophic cardiomyopathy and has the potential to influence their surgical management. However, for medical treatment of hypertrophic cardiomyopathy, TTE is sufficient.

  3. Hypertrophic cardiomyopathy and hyperthyroidism: a report of three cases

    PubMed Central

    Symons, C.; Richardson, P. J.; Feizi, O.

    1974-01-01

    Symons, C., Richardson, P. J., and Feizi, O. (1974).Thorax, 29, 713-719. Hypertrophic cardiomyopathy and hyperthyroidism. The combination of hypertrophic cardiomyopathy and hyperthyroidism gives rise to a complex clinical picture as some of the symptoms and signs may be common to both conditions. The presentation and investigation of three patients are reported. In one patient there was evidence of progression from the hypertrophic obstructive phase to that associated with loss of outflow tract obstruction. The echocardiogram was especially useful in assessing the presence or absence of hypertrophic disease in the thyrotoxic subject. It is suggested that the long continued high-output circulatory state in clinically undetected hyperthyroidism may prove to be a stimulus for unrestrained cardiac muscle hypertrophy. Images PMID:4281112

  4. Advances in medical treatment of hypertrophic cardiomyopathy.

    PubMed

    Hamada, Mareomi; Ikeda, Shuntaro; Shigematsu, Yuji

    2014-07-01

    We reviewed the natural history of patients with hypertrophic cardiomyopathy (HCM). The effect of medical treatments on natural history, left ventricular (LV) functions and LV remodeling was also evaluated. Sudden cardiac death and end-stage heart failure are the most serious complications of HCM. Age <30 years and a family history of sudden premature death are risk factors for sudden cardiac death in HCM patients. End-stage heart failure is not a specific additional phenomenon observed in patients with HCM, but is the natural course of the disease in most of those patients. After the occurrence of heart failure, the progression to cardiac death is very rapid. Young age at diagnosis, a family history of HCM, and greater wall thickness are associated with a greater likelihood of developing end-stage heart failure. Neither beta-blockers nor calcium antagonists can prevent this transition. The class Ia antiarrhythmic drugs, disopyramide and cibenzoline are useful for the reduction of LV pressure gradient. Unlike disopyramide, cibenzoline has little anticholinergic activity; therefore, this drug can be easily adapted to long-term use. In addition to the reduction in LV pressure gradient, cibenzoline can improve LV diastolic dysfunction, and induce regression of LV hypertrophy in patients with HCM. A decrease in intracellular Ca(2+) concentration through the activation of the Na(+)/Ca(2+) exchanger associated with cibenzoline therapy is likely to be closely related with the improvement in HCM-related disorders. It is possible that cibenzoline can prevent the progression from typical HCM to end-stage heart failure.

  5. A Tension-Based Model Distinguishes Hypertrophic versus Dilated Cardiomyopathy.

    PubMed

    Davis, Jennifer; Davis, L Craig; Correll, Robert N; Makarewich, Catherine A; Schwanekamp, Jennifer A; Moussavi-Harami, Farid; Wang, Dan; York, Allen J; Wu, Haodi; Houser, Steven R; Seidman, Christine E; Seidman, Jonathan G; Regnier, Michael; Metzger, Joseph M; Wu, Joseph C; Molkentin, Jeffery D

    2016-05-19

    The heart either hypertrophies or dilates in response to familial mutations in genes encoding sarcomeric proteins, which are responsible for contraction and pumping. These mutations typically alter calcium-dependent tension generation within the sarcomeres, but how this translates into the spectrum of hypertrophic versus dilated cardiomyopathy is unknown. By generating a series of cardiac-specific mouse models that permit the systematic tuning of sarcomeric tension generation and calcium fluxing, we identify a significant relationship between the magnitude of tension developed over time and heart growth. When formulated into a computational model, the integral of myofilament tension development predicts hypertrophic and dilated cardiomyopathies in mice associated with essentially any sarcomeric gene mutations, but also accurately predicts human cardiac phenotypes from data generated in induced-pluripotent-stem-cell-derived myocytes from familial cardiomyopathy patients. This tension-based model also has the potential to inform pharmacologic treatment options in cardiomyopathy patients.

  6. Stress cardiomyopathy in a patient with hypertrophic cardiomyopathy and myocardial bridging

    PubMed Central

    Benavides, Miguel; Vinardell, Juan M; Arenas, Ivan; Santana, Orlando

    2017-01-01

    Stress cardiomyopathy is an acquired cardiomyopathy of unknown aetiology. It usually occurs in women over the age of 70 who have experienced physical or emotional stress. It is most commonly characterised by a transient, left ventricular systolic dysfunction in the apical portion and hyperkinesia in the basal segments, without obstructive coronary artery disease. Its association with obstructive hypertrophic cardiomyopathy and myocardial bridging is rare. Herein, we present such a case. PMID:28228389

  7. Hypertrophic Cardiomyopathy: Practical Steps for Preventing Sudden Death.

    ERIC Educational Resources Information Center

    Maron, Barry J.

    2002-01-01

    Hypertrophic cardiomyopathy (HCM) is a rare cause of death among athletes, with deaths occurring in young, apparently healthy people. Differentiating HCM from conditioning hypertrophy is challenging. Routine detection involves family history, physical examination, electrocardiography, and echocardiography. Keys to differential diagnosis include…

  8. Hypertrophic cardiomyopathy in infants: clinical features and natural history

    SciTech Connect

    Maron, B.J.; Tajik, A.J.; Ruttenberg, H.D.; Graham, T.P.; Atwood, G.F.; Victorica, B.E.; Lie, J.T.; Roberts, W.C.

    1982-01-01

    The clinical and morphologic features of hypertrophic cardiomyopathy in 20 patients recognized as having cardiac disease in the first year of life are described. Fourteen of these 20 infants were initially suspected of having heart disease solely because a heart murmur was identified. However, the infants showed a variety of clinical findings, including signs of marked congestive heart failure (in the presence of nondilated ventricular cavities and normal or increased left ventricular contractility) and substantial cardiac enlargement on chest radiograph. Other findings were markedly different from those usually present in older children and adults with hypertrophic cardiomyopathy (e.g., right ventricular hypertrophy on the ECG and cyanosis). Consequently, in 14 infants, the initial clinical diagnosis was congenital cardiac malformation other than hypertrophic cardiomyopathy. The clinical course was variable in these patients, but the onset of marked congestive heart failure in the first year of life appeared to be an unfavorable prognostic sign; nine of the 11 infants with congestive heart failure died within the first year of life. In infants with hypertrophic cardiomyopathy, unlike older children and adults with this condition, sudden death was less common (two patients) than death due to progressive congestive heart failure.

  9. Evolutionary change mimicking apical hypertrophic cardiomyopathy in a patient with takotsubo cardiomyopathy.

    PubMed

    Hwang, Hui-Jeong; Lee, Hyae-Min; Yang, In-Ho; Kim, Dong-Hee; Byun, Jong-Kyu; Sohn, Il Suk

    2014-11-01

    In this report, we introduce a case of thickening of the involved left ventricular apical segment on echocardiography and deep T-wave inversions in precordial leads on electrocardiography transiently seen in the course of recovery from biventricular takotsubo cardiomyopathy, mimicking apical hypertrophic cardiomyopathy. This result suggests that the echocardiographic finding of transient myocardial edema can be identified by cardiac magnetic resonance imaging in takotsubo cardiomyopathy. Additionally, it persisted a few weeks after full functional recovery. We believe that this case will contribute in part toward clarifying the pathophysiology of takotsubo cardiomyopathy.

  10. Genetics Home Reference: familial hypertrophic cardiomyopathy

    MedlinePlus

    ... cardiomyopathy is a heart condition characterized by thickening (hypertrophy) of the heart (cardiac) muscle . Thickening usually occurs ... also lead to symptoms of the condition. Cardiac hypertrophy often begins in adolescence or young adulthood, although ...

  11. Hypertrophic Cardiomyopathy Registry (HCMR): The rationale and design of an international, observational study of hypertrophic cardiomyopathy

    PubMed Central

    Kramer, Christopher M.; Appelbaum, Evan; Desai, Milind Y.; Desvigne-Nickens, Patrice; DiMarco, John P.; Friedrich, Matthias G.; Geller, Nancy; Heckler, Sarahfaye; Ho, Carolyn Y.; Jerosch-Herold, Michael; Ivey, Elizabeth A.; Keleti, Julianna; Kim, Dong-Yun; Kolm, Paul; Kwong, Raymond Y.; Maron, Martin S.; Schulz-Menger, Jeanette; Piechnik, Stefan; Watkins, Hugh; Weintraub, William S.; Wu, Pan; Neubauer, Stefan

    2015-01-01

    Hypertrophic cardiomyopathy (HCM) is the most common monogenic heart disease with a frequency as high as 1 in 200. In many cases, HCM is caused by mutations in genes encoding the different components of the sarcomere apparatus. HCM is characterized by unexplained left ventricular hypertrophy (LVH), myofibrillar disarray, and myocardial fibrosis. The phenotypic expression is quite variable. While the majority of patients with HCM are asymptomatic, serious consequences are experienced in a subset of affected individuals who present initially with sudden cardiac death (SCD) or progress to refractory heart failure (HF). The HCMR study is a National Heart Lung and Blood Institute (NHLBI)-sponsored 2750 patient, 41 site, international registry and natural history study designed to address limitations in extant evidence to improve prognostication in HCM (NCT01915615). In addition to collection of standard demographic, clinical, and echocardiographic variables, patients will undergo state-of-the-art cardiac magnetic resonance (CMR) for assessment of left ventricular (LV) mass and volumes as well as replacement scarring and interstitial fibrosis. In addition, genetic and biomarker analysis will be performed. HCMR has the potential to change the paradigm of risk stratification in HCM, using novel markers to identify those at higher risk. PMID:26299218

  12. [Risk stratification of sudden death in hypertrophic cardiomyopathy in 2016].

    PubMed

    Dubourg, Olivier; Charron, Philippe; Sirol, Marc; Siam-Tsieu, Valérie; Mansencal, Nicolas

    2016-10-01

    Patients with hypertrophic cardiomyopathy (HCM) are at an increased risk of death from many causes and sudden cardiac death is one of them. The study of the sudden cardiac death of patients with HCM has allowed the identification of risk factors and among them major risk factor are: family history of sudden cardiac death, the occurrence of syncope/dizziness, the existence of non-sustained ventricular tachycardia an abnormal blood pressure response during stress test, presence of severe left ventricular hypertrophy≥30mm. Risk stratification for sudden cardiac death is essential, for symptomatic or asymptomatic HCM patients. Two approaches are possible: the classical approach or risk stratification methods with major risk factors and the new approach using the risk-calculator recommended by the ESC. Both methods are not in opposition but complementary. The risk stratification in hypertrophic cardiomyopathy should be still improved to be sure that only the most high-risk patients receive an implantable cardiac defibrillator.

  13. Atrial Myxoma in a Patient with Hypertrophic Cardiomyopathy

    PubMed Central

    Abdou, Mahmoud; Hayek, Salim; Williams, Byron R.

    2013-01-01

    Atrial myxoma is the most common primary cardiac tumor. Patients with atrial myxoma typically present with obstructive, embolic, or systemic symptoms; asymptomatic presentation is very rare. To our knowledge, isolated association of atrial myxoma with hypertrophic cardiomyopathy has been reported only once in the English-language medical literature. We report the case of an asymptomatic 71-year-old woman with known hypertrophic cardiomyopathy in whom a left atrial mass was incidentally identified on cardiac magnetic resonance images. After surgical excision of the mass and partial excision of the left atrial septum, histopathologic analysis confirmed the diagnosis of atrial myxoma. The patient was placed on preventive implantable cardioverter-defibrillator therapy and remained asymptomatic. The management of asymptomatic cardiac myxoma is a topic of debate, because no reports definitively favor either conservative or surgical measures. PMID:24082380

  14. Atrial fibrillation in hypertrophic cardiomyopathy: mechanisms, embolic risk and prognosis.

    PubMed

    Nair, Ajith G; Fischer, Avi G

    2006-12-01

    Hypertrophic cardiomyopathy (HCM) is associated with an increased incidence of supraventricular and ventricular arrhythmias. Atrial fibrillation (AF) is the most common arrhythmia in HCM with a prevalence of 20% and an annual incidence of two percent per year. Increased left atrial size and volume along with impaired left atrial function confer an increased likelihood of AF. The onset of AF is often accompanied by a decrease in functional status in conjunction with an increased risk of stroke and overall mortality.

  15. Reversible transition from a hypertrophic to a dilated cardiomyopathy

    PubMed Central

    Spillmann, Frank; Kühl, Uwe; Van Linthout, Sophie; Dominguez, Fernando; Escher, Felicitas; Schultheiss, Heinz‐Peter; Pieske, Burkert

    2015-01-01

    Abstract We report the case of a 17‐year‐old female patient with known hypertrophic cardiomyopathy and a Wolff‐Parkinson‐White syndrome. She came to our department for further evaluation of a new diagnosed dilated cardiomyopathy characterized by an enlargement of the left ventricle and a fall in ejection fraction. Clinically, she complained about atypical chest pain, arrhythmic episodes with presyncopal events, and dyspnea (NYHA III) during the last 6 months. Non‐invasive and invasive examinations including magnetic resonance imaging, electrophysiological examinations, and angiography did not lead to a conclusive diagnosis. Therefore, endomyocardial biopsies (EMBs) were taken to investigate whether a specific myocardial disease caused the impairment of the left ventricular function. EMB analysis resulted in the diagnosis of a virus‐negative, active myocarditis. Based on this diagnosis, an immunosuppressive treatment with prednisolone and azathioprine was started, which led to an improvement of cardiac function and symptoms within 3 months after initiating therapy. In conclusion, we show that external stress triggered by myocarditis can induce a reversible transition from a hypertrophic cardiomyopathy to a dilated cardiomyopathy phenotype. This case strongly underlines the need for a thorough and invasive examination of heart failure of unknown causes, including EMB investigations as recommend by the actual ESC position statement. PMID:27774273

  16. Hearing Profile in Patients with Dilated and Hypertrophic Cardiomyopathies

    PubMed Central

    El-Zarea, Gehan Abd El-Rahman; Hassan, Yasser Elsayed Mohamed; Mahmoud, Ahmed Mohamed Ahmed

    2016-01-01

    Introduction Cardiomyopathy may cause disruptions in the micro-vascular system of the stria vascularis in the cochlea, and, subsequently, may result in cochlear degeneration. Degeneration in the stria vascularis affects the physical and chemical processes in the organ of Corti, thereby causing a possible hearing impairment. The objective of this study was to assess the hearing profiles of patients with dilated and hypertrophic cardiomyopathies to determine the relationship between the degree of hearing loss and the degree and duration of the disease and to compare the dilated and hypertrophic cardiomyopathies as regards hearing profile. Methods In this case control study, we studied 21 patients (cases/study group/group 1) and 15 healthy individuals (controls/group 2). Six patients (group 1a) had hypertrophic cardiomyopathy (HCM), and 15 patients (group 1b) had dilated cardiomyopathy (DCM). The data were analyzed using the t-test, chi-squared test, Kruskal-Wallis test, and the Multiple Mann-Whitney test. Results The results of this study showed that 80% of those patients with DCM (group 1b) had bilateral sensorineural hearing loss (SNHL), and 100% of the patients with HCM (group 1a) had mild to severe bilateral sloping SNHL. Distortion Product Otoacoustic Emissions (DPOAEs) were present in 14% of the study group and in 100 % of the control group. The results of the measurements of auditory brainstem response (ABR) showed that 50% of the study group had abnormal latencies compared to the control group, and there was no correlation between the duration of the disease and the degree of hearing loss or DPOAE. Fifty percent of the patients with HCM and 35% of the patients with DCM had positive family histories of similar conditions, and 35% of those with HCM had a positive family history of sudden death. Conclusion The results of this study suggested that the link between heart disease and hearing loss and early identification of hearing loss in patients with

  17. Echocardiographic sign of right-sided hypertrophic obstructive cardiomyopathy.

    PubMed Central

    Cardiel, E A; Alonso, M; Delcan, J L; Menarguez, L

    1978-01-01

    The echocardiographic and haemodynamic findings with a patient with hypertrophic obstructive cardiomyopathy (HOCM) and dynamic subpulmonary stenosis, without left ventricular gradient, are described. The echocardiogram shows not only asymmetric septal hypertrophy, systolic anterior movement of the anterior mitral leaflet, and midsystolic collapse of the aortic valve, but also increase in the right ventricular wall echoes and systolic collapse of the pulmonary valve. We believe that in the absence of pulmonary hypertension these signs, particularly the systolic closing movement of the pulmonary valve cusp, may suggest right ventricular obstruction in HOCM. Images PMID:568930

  18. Atrial fibrillation and hypertrophic cardiomyopathy: who to anticoagulate?

    PubMed

    Frontera, Antonio; Wilson, D G; Sekhon, H; Duncan, E R; Thomas, G

    2015-10-01

    Hypertrophic cardiomyopathy (HCM) is one of the most common genetic cardiac conditions. Atrial fibrillation (AF) has been demonstrated to be the most frequent arrhythmia encountered in HCM patients. Research focusing on AF and embolic stroke in HCM patients has been sparse and the sample size of most studies is small. The prognostic significance of AF in HCM patients is still not well known. The aim of this article is to provide further understanding of the anti-coagulation requirement of HCM patients with AF.

  19. Surgical Myectomy after Failed Ablation for Hypertrophic Obstructive Cardiomyopathy

    PubMed Central

    Bougioukas, Ioannis; Hoppe, Uta; Danner, Bernhard; Schoendube, Friedrich A.

    2016-01-01

    Background Hypertrophic cardiomyopathy is a genetic disease of the myocardial sarcolemma characterized by left ventricular hypertrophy. When obstruction to the left ventricular outflow tract is present and symptoms are refractory to medication, surgical myectomy or alcohol septal ablation is indicated. Case Description We report a case of a patient presented for myectomy due to recurrence only 1 year after alcohol ablation. Interesting findings were a firm subaortic membrane and a direct insertion of the papillary muscle into the mitral valve. Conclusion After myectomy and extensive papillary muscle mobilization, a significant relief of obstruction was achieved. PMID:28018818

  20. Hypertrophic cardiomyopathy in a mixed breed cat family.

    PubMed

    Nakagawa, Kiyoshi; Takemura, Naoyuki; Machida, Noboru; Kawamura, Masamichi; Amasaki, Hajime; Hirose, Hisashi

    2002-07-01

    A spayed female mixed cat (case 1) and its female offspring, the result of a pairing between case 1 and its male sibling, were diagnosed with hypertrophic cardiomyopathy (HCM). A pedigree survey revealed that the prevalence of HCM was at least 12.5% in the family, which was considered to be significantly higher than that in a hospital-based population (approximately 1.6%). Thus, this finding seems to support the suspected occurrence of familial HCM in this group of related cats.

  1. Percutaneous transluminal septal myocardial ablation in hypertrophic cardiomyopathy

    PubMed Central

    van der Lee, C.; Foley, D.P.; Vletter, W.B.; ten Cate, F.J.; Kofflard, M.J.M.

    2001-01-01

    Background Percutaneous transluminal septal myocardial ablation (PTSMA) is a new interventional technique to treat patients with hypertrophic cardiomyopathy. Methods Small doses of ethanol 96% were injected into a targeted septal artery causing a chemical myocardial infarction. Three patients were evaluated, including a follow-up of three months. Results There were no complications during the procedure LVOT gradient was reduced from 120±140 mmHg. At follow-up, all three patients showed improvement in validity. Conclusion The method requires an echocardiographic contrast determination of the myocardium at risk for ethanol treatment, in addition to haemodynamic monitoring. ImagesFigure 1Figure 2Figure 3A PMID:25696698

  2. Ehlers-Danlos Syndrome associated with cardiomyopathy hypertrophic obstructive.

    PubMed

    Pinto, Raimundo José Almeida de Oliveira; Santos, Adaílton Araújo dos; Azevedo, Mablo de Castro; Meira, Saulo Sacramento

    2015-01-01

    Ehlers-Danlos syndrome is a rare clinical condition caused by a genetic change that results in the formation of structurally or functionally altered collagen. The clinical manifestations are varied, being the most obvious skin hypermotility and increased joint flexibility, although other systems - such as cardiovascular, respiratory and neurological - may also be affected. This paper presents the report of a patient who sought medical attention with complaints of atypical chest pain. Clinical evaluation enabled hypothetical diagnosis of hypertrophic obstructive cardiomyopathy and Ehlers-Danlos syndrome. Initial electrocardiogram, echocardiogram and 24 hours holter allowed the confirmation of the first hypothesis. A skin biopsy performed later associated clinical data and confirmed the second hypothesis.

  3. Two different cardiomyopathies in a single patient : hypertrophic cardiomyopathy and left ventricular noncompaction.

    PubMed

    Sunbul, M; Ozben, B; Mutlu, B

    2013-05-01

    Hypertrophic cardiomyopathy is a complex and relatively common genetic disorder characterized by left ventricular (LV) hypertrophy, usually associated with a nondilated and hyperdynamic chamber with heterogeneous phenotypic expression and clinical course. On the other hand, LV noncompaction is an uncommon cardiomyopathy characterized by the persistence of fetal myocardium with a pattern of prominent trabecular meshwork and deep intertrabecular recesses, systolic dysfunction, and LV dilatation. We report a 29-year-old man with these two different inherent conditions. Our case raises the possibility of a genetic mutation common to these two clinical entities or different gene mutations existing in the same individual.

  4. The genetic basis of hypertrophic cardiomyopathy in cats and humans.

    PubMed

    Kittleson, Mark D; Meurs, Kathryn M; Harris, Samantha P

    2015-12-01

    Mutations in genes that encode for muscle sarcomeric proteins have been identified in humans and two breeds of domestic cats with hypertrophic cardiomyopathy (HCM). This article reviews the history, genetics, and pathogenesis of HCM in the two species in order to give veterinarians a perspective on the genetics of HCM. Hypertrophic cardiomyopathy in people is a genetic disease that has been called a disease of the sarcomere because the preponderance of mutations identified that cause HCM are in genes that encode for sarcomeric proteins (Maron and Maron, 2013). Sarcomeres are the basic contractile units of muscle and thus sarcomeric proteins are responsible for the strength, speed, and extent of muscle contraction. In people with HCM, the two most common genes affected by HCM mutations are the myosin heavy chain gene (MYH7), the gene that encodes for the motor protein β-myosin heavy chain (the sarcomeric protein that splits ATP to generate force), and the cardiac myosin binding protein-C gene (MYBPC3), a gene that encodes for the closely related structural and regulatory protein, cardiac myosin binding protein-C (cMyBP-C). To date, the two mutations linked to HCM in domestic cats (one each in Maine Coon and Ragdoll breeds) also occur in MYBPC3 (Meurs et al., 2005, 2007). This is a review of the genetics of HCM in both humans and domestic cats that focuses on the aspects of human genetics that are germane to veterinarians and on all aspects of feline HCM genetics.

  5. Subaortic and midventricular obstructive hypertrophic cardiomyopathy with extreme segmental hypertrophy

    PubMed Central

    Efthimiadis, Georgios K; Giannakoulas, Georgios; Parcharidou, Despina G; Ziakas, Antonios G; Papadopoulos, Christodoulos E; Karoulas, Takis; Pliakos, Christodoulos; Parcharidis, Georgios

    2007-01-01

    Background Subaortic and midventricular hypertrophic cardiomyopathy in a patient with extreme segmental hypertrophy exceeding the usual maximum wall thickness reported in the literature is a rare phenomenon. Case Presentation A 19-year-old man with recently diagnosed hypertrophic cardiomyopathy (HCM) was referred for sudden death risk assessment. The patient had mild exertional dyspnea (New York Heart Association functional class II), but without syncope or chest pain. There was no family history of HCM or sudden death. A two dimensional echocardiogram revealed an asymmetric type of LV hypertrophy; anterior ventricular septum = 49 mm; posterior ventricular septum = 20 mm; anterolateral free wall = 12 mm; and posterior free wall = 6 mm. The patient had 2 types of obstruction; a LV outflow obstruction due to systolic anterior motion of both mitral leaflets (Doppler-estimated 38 mm Hg gradient at rest); and a midventricular obstruction (Doppler-estimated 43 mm Hg gradient), but without apical aneurysm or dyskinesia. The patient had a normal blood pressure response on exercise test and no episodes of non-sustained ventricular tachycardia in 24-h ECG recording. Cardiac MRI showed a gross late enhancement at the hypertrophied septum. Based on the extreme degree of LV hypertrophy and the myocardial hyperenhancement, an implantation of a cardioverter-defibrillator was recommended prophylactically for primary prevention of sudden death. Conclusion Midventricular HCM is an infrequent phenotype, but may be associated with an apical aneurysm and progression to systolic dysfunction (end-stage HCM). PMID:17349063

  6. Down Syndrome with Complete Atrioventricular Septal Defect, Hypertrophic Cardiomyopathy, and Pulmonary Vein Stenosis.

    PubMed

    Mahadevaiah, Guruprasad; Gupta, Manoj; Ashwath, Ravi

    2015-10-01

    The prevalence of congenital heart disease in infants with Down syndrome is 40%, compared with 0.3% in children who have normal chromosomes. Atrioventricular and ventricular septal defects are often associated with chromosomal aberrations, such as in trisomy 21, whereas hypertrophic cardiomyopathy is chiefly thought to be secondary to specific gene mutations. We found only one reported case of congenital hypertrophic cardiomyopathy and atrioventricular septal defect in an infant with Down syndrome. Here, we report atrioventricular septal defect, hypertrophic cardiomyopathy, and pulmonary vein stenosis in a neonate with Down syndrome-an apparently unique combination. In addition, we discuss the relevant medical literature.

  7. An Unusual Type of Localized Hypertrophic Cardiomyopathy With Wolf Parkinson White Syndrome Presenting With Pulmonary Edema

    PubMed Central

    Vatan, Mehmet Bulent; Gunduz, Huseyin; Gurel, Safiye; Kocayigit, Ibrahim; Vural, Ahmet; Demirtas, Saadet; Cakar, Mehmet Akif; Gunduz, Yasemin

    2012-01-01

    Hypertrophic cardiomyopathy (HCM) is an autosomal dominant heart disease that is the most common genetic cardiac disorder. The disease is characterized by excessive thickening of the left ventricular myocardium. The anterior portion of the interventricular ventricular septum is often involved. Asymmetric hypertrophy of apical site, left ventricular free wall, and right ventricle are less common in hypertrophic cardiomyopathy that occur in 1% cases. We report a case of a patient with an unusual type of hypertrophic cardiomyopathy and Wolf Parkinson White (WPW) presenting with pulmonary edema.

  8. Determination of multidirectional myocardial deformations in cats with hypertrophic cardiomyopathy by using two-dimensional speckle-tracking echocardiography.

    PubMed

    Suzuki, Ryohei; Mochizuki, Yohei; Yoshimatsu, Hiroki; Teshima, Takahiro; Matsumoto, Hirotaka; Koyama, Hidekazu

    2017-02-01

    Objectives Hypertrophic cardiomyopathy, a primary disorder of the myocardium, is the most common cardiac disease in cats. However, determination of myocardial deformation with two-dimensional speckle-tracking echocardiography in cats with various stages of hypertrophic cardiomyopathy has not yet been reported. This study was designed to measure quantitatively multidirectional myocardial deformations of cats with hypertrophic cardiomyopathy. Methods Thirty-two client-owned cats with hypertrophic cardiomyopathy and 14 healthy cats serving as controls were enrolled and underwent assessment of myocardial deformation (peak systolic strain and strain rate) in the longitudinal, radial and circumferential directions. Results Longitudinal and radial deformations were reduced in cats with hypertrophic cardiomyopathy, despite normal systolic function determined by conventional echocardiography. Cats with severely symptomatic hypertrophic cardiomyopathy also had lower peak systolic circumferential strain, in addition to longitudinal and radial strain. Conclusions and relevance Longitudinal and radial deformation may be helpful in the diagnosis of hypertrophic cardiomyopathy. Additionally, the lower circumferential deformation in cats with severe hypertrophic cardiomyopathy may contribute to clinical findings of decompensation, and seems to be related to severe cardiac clinical signs. Indices of multidirectional myocardial deformations by two-dimensional speckle-tracking echocardiography may be useful markers and help to distinguish between cats with hypertrophic cardiomyopathy and healthy cats. Additionally, they may provide more detailed assessment of contractile function in cats with hypertrophic cardiomyopathy.

  9. Ehlers-Danlos Syndrome associated with cardiomyopathy hypertrophic obstructive*

    PubMed Central

    Pinto, Raimundo José Almeida de Oliveira; dos Santos, Adaílton Araújo; Azevedo, Mablo de Castro; Meira, Saulo Sacramento

    2015-01-01

    Ehlers-Danlos syndrome is a rare clinical condition caused by a genetic change that results in the formation of structurally or functionally altered collagen. The clinical manifestations are varied, being the most obvious skin hypermotility and increased joint flexibility, although other systems - such as cardiovascular, respiratory and neurological - may also be affected. This paper presents the report of a patient who sought medical attention with complaints of atypical chest pain. Clinical evaluation enabled hypothetical diagnosis of hypertrophic obstructive cardiomyopathy and Ehlers-Danlos syndrome. Initial electrocardiogram, echocardiogram and 24 hours holter allowed the confirmation of the first hypothesis. A skin biopsy performed later associated clinical data and confirmed the second hypothesis. PMID:26312722

  10. Fabry Disease Presenting with Hypertrophic Cardiomyopathy and Tricuspid Regurgitation

    PubMed Central

    Cho, Sang-Cheol; Yoo, Han-Wook; Lee, Jae Won; Jang, Jeong Yoon; Heo, Ran

    2016-01-01

    A 71-year-old female who was diagnosed with nonobstructive hypertrophic cardiomyopathy since 1999 presented with dyspnea and severe edema on both legs. For the management of her symptom, cardiac surgery including tricuspid annuloplasty, Maze operation and right atrial reduction plasty was performed. During follow-up after cardiac surgery, a plasma α-galactosidase activity was checked for the screening of Fabry disease and the result was around lower normal limit. DNA analysis was implemented for confirmation and it revealed a heterozygote α-galactosidase mutation at exon 6 [c.901C>T (p.Arg301Ter)]. This case suggests that Fabry disease might be easily undetected, and clinical suspicion is critical. PMID:28090261

  11. Hypertrophic cardiomyopathy and ultra-endurance running - two incompatible entities?

    PubMed Central

    2011-01-01

    Regular and prolonged exercise is associated with increased left ventricular wall thickness that can overlap with hypertrophic cardiomyopathy (HCM). Differentiating physiological from pathological hypertrophy has important implications, since HCM is the commonest cause of exercise-related sudden cardiac death in young individuals. Most deaths have been reported in intermittent 'start-stop' sports such as football (soccer) and basketball. The theory is that individuals with HCM are unable to augment stroke volume sufficiently to meet the demands of endurance sports and are accordingly 'selected-out' of participation in such events. We report the case of an ultra-endurance athlete with 25 years of > 50 km competitive running experience, with genetically confirmed HCM; thereby demonstrating that these can be two compatible entities. PMID:22122802

  12. Hypertrophic cardiomyopathy: a heart in need of an energy bar?

    PubMed Central

    Vakrou, Styliani; Abraham, M. Roselle

    2014-01-01

    Hypertrophic cardiomyopathy (HCM) has been recently recognized as the most common inherited cardiovascular disorder, affecting 1 in 500 adults worldwide. HCM is characterized by myocyte hypertrophy resulting in thickening of the ventricular wall, myocyte disarray, interstitial and/or replacement fibrosis, decreased ventricular cavity volume and diastolic dysfunction. HCM is also the most common cause of sudden death in the young. A large proportion of patients diagnosed with HCM have mutations in sarcomeric proteins. However, it is unclear how these mutations lead to the cardiac phenotype, which is variable even in patients carrying the same causal mutation. Abnormalities in calcium cycling, oxidative stress, mitochondrial dysfunction and energetic deficiency have been described constituting the basis of therapies in experimental models of HCM and HCM patients. This review focuses on evidence supporting the role of cellular metabolism and mitochondria in HCM. PMID:25191275

  13. ICD Therapy for Primary Prevention in Hypertrophic Cardiomyopathy

    PubMed Central

    Trivedi, Amar

    2016-01-01

    Hypertrophic cardiomyopathy (HCM) is a common and heterogeneous disorder that increases an individual’s risk of sudden cardiac death (SCD). This review article discusses the relevant factors that are involved in the challenge of preventing SCD in patients with HCM. The epidemiology of SCD in patients is reviewed as well as the structural and genetic basis behind ventricular arrhythmias in HCM. The primary prevention of SCD with implantable cardioverter-defibrillator (ICD) therapy is the cornerstone of modern treatment for individuals at high risk of SCD. The focus here is on the current and emerging predictors of SCD as well as risk stratification recommendations from both North American and European guidelines. Issues related to ICD implantation, such as programming, complications and inappropriate therapies, are discussed. The emerging role of the fully subcutaneous ICD and the data regarding its implantation are reviewed. PMID:28116084

  14. A new era in clinical genetic testing for hypertrophic cardiomyopathy.

    PubMed

    Wheeler, Matthew; Pavlovic, Aleksandra; DeGoma, Emil; Salisbury, Heidi; Brown, Colleen; Ashley, Euan A

    2009-12-01

    Building on seminal studies of the last 20 years, genetic testing for hypertrophic cardiomyopathy (HCM) has become a clinical reality in the form of targeted exonic sequencing of known disease-causing genes. This has been driven primarily by the decreasing cost of sequencing, but the high profile of genome-wide association studies, the launch of direct-to-consumer genetic testing, and new legislative protection have also played important roles. In the clinical management of hypertrophic cardiomyopathy, genetic testing is primarily used for family screening. An increasing role is recognized, however, in diagnostic settings: in the differential diagnosis of HCM; in the differentiation of HCM from hypertensive or athlete's heart; and more rarely in preimplantation genetic diagnosis. Aside from diagnostic clarification and family screening, use of the genetic test for guiding therapy remains controversial, with data currently too limited to derive a reliable mutation risk prediction from within the phenotypic noise of different modifying genomes. Meanwhile, the power of genetic testing derives from the confidence with which a mutation can be called present or absent in a given individual. This confidence contrasts with our more limited ability to judge the significance of mutations for which co-segregation has not been demonstrated. These variants of "unknown" significance represent the greatest challenge to the wider adoption of genetic testing in HCM. Looking forward, next-generation sequencing technologies promise to revolutionize the current approach as whole genome sequencing will soon be available for the cost of today's targeted panel. In summary, our future will be characterized not by lack of genetic information but by our ability to effectively parse it.

  15. Marked left ventricular hypertrophy mimicking hypertrophic cardiomyopathy associated with steroid therapy for congenital adrenal hyperplasia.

    PubMed

    Scirè, Giuseppe; D'Anella, Giorgio; Cristofori, Laura; Mazzuca, Valentina; Cianfarani, Stefano

    2007-06-01

    We describe a child treated with high-dose steroid therapy for congenital adrenal hyperplasia who showed marked left ventricular hypertrophy mimicking hypertrophic cardiomyopathy associated with steroid therapy for congenital adrenal hyperplasia. Cardiomyopathy reversed completely when an appropriate steroid therapeutic regimen was established.

  16. [The thickness/radius ratio (t/r) in patients with dilated and hypertrophic cardiomyopathy].

    PubMed

    Guadalajara, J F; Valenzuela, F; Martínez Sánchez, C; Huerta, D

    1990-01-01

    We studied 17 patients with cardiomyopathy (10 hypertrophic and 7 dilated). With two-dimensional echocardiography, we obtained a short axis view at the level of papillary muscle. We calculated the ratio between thickness (h), of ventricular wall and cavity's radius (r) in diastole and systole (h/r ratio). Hypertrophic cardiomyopathy has a high h/r ratio in diastole (inappropriate hypertrophy), hypercontractility and low and systolic wall stress. Dilated cardiomyopathy has a low diastolic h/r ratio (inadequate hypertrophy) with low contractility and elevated end-systolic, wall stress. We discuss the mechanisms and consequences of different patterns of hypertrophy on the ventricular performance.

  17. Progress with genetic cardiomyopathies: screening, counseling, and testing in dilated, hypertrophic, and arrhythmogenic right ventricular dysplasia/cardiomyopathy.

    PubMed

    Hershberger, Ray E; Cowan, Jason; Morales, Ana; Siegfried, Jill D

    2009-05-01

    This review focuses on the genetic cardiomyopathies: principally dilated cardiomyopathy, with salient features of hypertrophic cardiomyopathy and arrhythmogenic right ventricular dysplasia/cardiomyopathy, regarding genetic etiology, genetic testing, and genetic counseling. Enormous progress has recently been made in identifying genetic causes for each cardiomyopathy, and key phenotype and genotype information is reviewed. Clinical genetic testing is rapidly emerging with a principal rationale of identifying at-risk asymptomatic or disease-free relatives. Knowledge of a disease-causing mutation can guide clinical surveillance for disease onset, thereby enhancing preventive and treatment interventions. Genetic counseling is also indicated for patients and their family members regarding the symptoms of their cardiomyopathy, its inheritance pattern, family screening recommendations, and genetic testing options and possible results.

  18. [Perioperative management for patients with hypertrophic cardiomyopathy undergoing noncardiac surgery].

    PubMed

    Okuyama, A; Goda, Y; Kawahigashi, H; Takita, K; Okuyama, M; Kubota, M

    1992-01-01

    We had two patients with hypertrophic cardiomyopathy for noncardiac surgeries. Case 1: A 74-year-old man for right nephrectomy received epidural lidocaine and nitrous oxide combined with 0.2-0.6% isoflurane. During the operation, heart rate and blood pressure were relatively unstable, but he woke up promptly after the operation. Early on the morning of the 2nd post-operative day, he was found dead on his bed. Case 2: A 52-year-old man for gastrectomy was anesthetized with nitrous oxide and halothane with continuous propranolol infusion. Through the operative period, heart rate and blood pressure were stable and postoperative course was uneventful. In these two patients, preoperative Holter ECG showed ventricular tachycardia, which may increase the risk of a sudden death. These cases demonstrate that general anesthesia with nitrous oxide combined with halothane, can be administered with a low risk in patients with HCM for noncardiac surgery and that postoperative intensive care unit monitoring is necessary for these patients for several days to prevent a sudden death.

  19. Vps34 regulates myofibril proteostasis to prevent hypertrophic cardiomyopathy

    PubMed Central

    Kimura, Hirotaka; Eguchi, Satoshi; Sasaki, Junko; Kuba, Keiji; Nakanishi, Hiroki; Yamazaki, Masakazu; Goto, Akiteru; Watanabe, Hiroyuki; Itoh, Hiroshi; Imai, Yumiko; Suzuki, Akira

    2017-01-01

    Hypertrophic cardiomyopathy (HCM) is a common heart disease with a prevalence of 1 in 500 in the general population. Several mutations in genes encoding cardiac proteins have been found in HCM patients, but these changes do not predict occurrence or prognosis and the molecular mechanisms underlying HCM remain largely elusive. Here we show that cardiac expression of vacuolar protein sorting 34 (Vps34) is reduced in a subset of HCM patients. In a mouse model, muscle-specific loss of Vps34 led to HCM-like manifestations and sudden death. Vps34-deficient hearts exhibited abnormal histopathologies, including myofibrillar disarray and aggregates containing αB-crystallin (CryAB). These features result from a block in the ESCRT-mediated proteolysis that normally degrades K63-polyubiquitinated CryAB. CryAB deposition was also found in myocardial specimens from a subset of HCM patients whose hearts showed decreased Vps34. Our results identify disruption of the previously unknown Vps34-CryAB axis as a potentially novel etiology of HCM. PMID:28097232

  20. Hypertrophic cardiomyopathy--state of the art in 2007.

    PubMed

    Monteiro, Silvia; Costa, Susana; Monteiro, Pedro; Gonçalves, Lino; Providência, Luís A

    2008-05-01

    Hypertrophic cardiomyopathy (HCM) is a primary disease of the sarcomere, with considerable genetic heterogeneity and variability in phenotypic expression, whose main complication is sudden cardiac death (SCD). Genetic aspects of HCM, its molecular pathophysiology and genotype-phenotype relationships are the subject of this review, which is aimed at better understanding of practical management in this patient population. As HCM is a genetic disease whose initial manifestation can be sudden death, it is essential to establish the diagnosis at an early stage, to proceed with risk stratification and implementation of SCD prevention strategies, and to promote genetic counseling of patients and screening of their families. Detection of pathological mutations through progressive sequencing of the genes most commonly involved is the most efficient way to diagnose HCM, even in the absence of clinical evidence of the disease. Identification of individuals at high risk of SCD is a major challenge in the management of this population, since SCD can be prevented by use of an implantable cardioverter-defibrillator. The selection of patients for prophylactic implantation of these devices, particularly those who have only one major risk factor, is currently the subject of controversy.

  1. Diastolic filling in a physical model of obstructive hypertrophic cardiomyopathy

    NASA Astrophysics Data System (ADS)

    Schovanec, Joseph; Samaee, Milad; Lai, Hong Kuan; Santhanakrishnan, Arvind

    2015-11-01

    Hypertrophic Cardiomyopathy (HCM) is an inherited heart disease that affects as much as one in 500 individuals, and is the most common cause of sudden death in young athletes. The myocardium becomes abnormally thick in HCM and deforms the internal geometry of the left ventricle (LV). Previous studies have shown that a vortex is formed during diastolic filling, and further that the dilated LV morphology seen in systolic heart failure results in altering the filling vortex from elliptical to spherical shape. We have also previously shown that increasing LV wall stiffness decreases the filling vortex circulation. However, alterations to intraventricular filling fluid dynamics due to an obstructive LV morphology and locally elevated wall stiffness (in the hypertrophied region) have not been previously examined from a mechanistic standpoint. We conducted an experimental study using an idealized HCM physical model and compared the intraventricular flow fields obtained from 2D PIV to a baseline LV physical model with lower wall stiffness and anatomical geometry. The obstruction in the HCM model leads to earlier breakdown of the filling vortex as compared to the anatomical LV. Intraventricular filling in both models under increased heart rates will be discussed.

  2. Hemolytic anemia in a patient with hypertrophic obstructive cardiomyopathy.

    PubMed

    Kubo, Toru; Kitaoka, Hiroaki; Terauchi, Yasunobu; Tamura, Shinjiro; Okawa, Makoto; Yamasaki, Naohito; Yabe, Toshikazu; Doi, Yoshinori L

    2010-01-01

    A 66-year-old woman was referred for further evaluation and treatment of normocytic and normochromic anemia with hemoglobin level of 8.6 g/dL. A peripheral blood smear showed fragmented erythrocytes. The patient was then referred to the department of cardiology because of systolic murmur, ECG abnormality, and red cell fragmentation. Transthoracic echocardiography revealed hypertrophic cardiomyopathy with particularly increased interventricular septal thickness of 24 mm and a hyperkinetic wall motion, resulting in marked obstruction to left ventricular outflow tract (pressure gradient of 200 mmHg). Mitral regurgitation due to systolic anterior motion of the mitral valve leaflets was also seen. The cause of anemia was thought to be mechanical intravascular hemolysis due to left ventricular outflow tract obstruction and mitral regurgitation. She was treated with atenolol and the class Ia antiarrhythmic drug cibenzoline to relieve the outflow tract obstruction, and the pressure gradient was reduced to 70 mmHg. After 3 months of treatment, her hemoglobin level had increased to 11.4 g/dL without additional treatment for anemia.

  3. The Ups and Downs of Genetic Diagnosis of Hypertrophic Cardiomyopathy.

    PubMed

    Gómez, Juan; Reguero, Julián R; Coto, Eliecer

    2016-01-01

    Massive DNA sequencing, also known as next-generation sequencing, has revolutionized genetic diagnosis. This technology has reduced the effort and cost needed to analyze several genes simultaneously and has made genetic evaluation available to a larger number of patients. In hypertrophic cardiomyopathy, genetic analysis has increased from the 3 main genes implicated in the disease (MYH7, MYBPC3, TNNT2) to sequencing of more than 20 related genes. Despite the advantages of acquiring this additional information, many patients show variants of uncertain significance (mainly amino acid changes), which may also be present in at least 1 healthy control undergoing genome sequencing. This will be a dead-end situation unless the variant can be demonstrated to be associated with the disease in the patient's family. In the absence of clear evidence that these variants are truly pathogenic, they cannot be used for reliable genetic counselling in family members. Massive sequencing also enables identification of new candidate genes, but again, the problem of variants of uncertain significance limits the success of these assessments.

  4. Successful management of hypertrophic cardiomyopathy in a Matschie's tree kangaroo (Dendrolagus matschiei).

    PubMed

    Fredholm, Daniel V; Jones, Ashley E; Hall, Natalie H; Russell, Kathleen; Heard, Darryl J

    2015-03-01

    A 3-yr-old, intact male Matschie's tree kangaroo (Dendrolagus matschiei) was examined for a 1-wk history of intermittent lethargy and tachypnea. An echocardiogram revealed concentric hypertrophy of the left ventricular free wall and interventricular septum. These findings were compared to measurements from healthy Matschie's tree kangaroos, supporting a diagnosis of hypertrophic cardiomyopathy. At the time of publication, the patient has been managed for over 11.5 yr, using a combination of enalapril, furosemide, diltiazem, and diet modifications. Hypertrophic cardiomyopathy should be considered as a differential diagnosis in tree kangaroos exhibiting signs of cardiovascular or respiratory distress. This case represents the first report of antemortem diagnosis and successful management of hypertrophic cardiomyopathy in a Matschie's tree kangaroo.

  5. Genetics of hypertrophic cardiomyopathy after 20 years: clinical perspectives.

    PubMed

    Maron, Barry J; Maron, Martin S; Semsarian, Christopher

    2012-08-21

    Hypertrophic cardiomyopathy (HCM) is the most common familial heart disease with vast genetic heterogeneity, demonstrated over the past 20 years. Mutations in 11 or more genes encoding proteins of the cardiac sarcomere (>1,400 variants) are responsible for (or associated with) HCM. Explosive progress achieved in understanding the rapidly evolving science underlying HCM genomics has resulted in fee-for-service testing, making genetic information widely available. The power of HCM mutational analysis, albeit a more limited role than initially envisioned, lies most prominently in screening family members at risk for developing disease and excluding unaffected relatives, which is information not achievable otherwise. Genetic testing also allows expansion of the broad HCM disease spectrum and diagnosis of HCM phenocopies with different natural history and treatment options, but is not a reliable strategy for predicting prognosis. Interfacing a heterogeneous disease such as HCM with the vast genetic variability of the human genome, and high frequency of novel mutations, has created unforeseen difficulties in translating complex science (and language) into the clinical arena. Indeed, proband diagnostic testing is often expressed on a probabilistic scale, which is frequently incompatible with clinical decision making. Major challenges rest with making reliable distinctions between pathogenic mutations and benign variants, and those judged to be of uncertain significance. Genotyping in HCM can be a powerful tool for family screening and diagnosis. However, wider adoption and future success of genetic testing in the practicing cardiovascular community depends on a standardized approach to mutation interpretation, and bridging the communication gap between basic scientists and clinicians.

  6. Altered patterns of cardiac intercellular junction distribution in hypertrophic cardiomyopathy.

    PubMed Central

    Sepp, R.; Severs, N. J.; Gourdie, R. G.

    1996-01-01

    OBJECTIVE: To examine the distribution pattern of intercellular junctions (the mechanically coupling desmosomes and the electrically coupling gap junctions) in hypertrophic cardiomyopathy (HCM) hearts showing myofibre disarray. DESIGN: Samples from six necropsied hearts were studied, representing the interventricular septum and the free walls of the left and right ventricles. Immunohistochemical labelling of desmoplakin was used as a marker for desmosomes, and of connexin43 as a marker for gap junctions, in single and double stainings. The slides were examined by confocal laser scanning microscopy. RESULTS: Marked disorganisation of intercalated discs was observed in areas featuring myofibre disarray. Besides overall derangement, localised abnormalities in desmosome organisation were evident, which included: (1) the formation of abnormally enlarged megadiscs; (2) the presence of intersecting disc structures; and (3) aberrant side to side desmosomal connections. Gap junctional abnormalities included: (1) random distribution of gap junctions over the surface of myocytes, rather than localisation to intercalated discs; (2) abundant side to side gap junction connections between adjacent myocytes; and (3) formation of abnormally shaped gap junctions. Circles of myocytes continuously interconnected by gap junctions were also observed. Regions of the diseased hearts lacking myofibre disarray, and control hearts of normal patients and patients with other cardiac diseases, did not show these alterations. CONCLUSIONS: The disorganisation of the intercellular junctions associated with myofibre disarray in HCM may play an important role in the pathophysiological manifestations of the disease. The remodelling of gap junction distribution may underlie the formation of an arrhythmogenic substrate, thereby contributing to the generation and maintenance of cardiac arrhythmias associated with HCM. Images PMID:8944586

  7. Clinical significance of giant negative T waves in hypertrophic cardiomyopathy

    SciTech Connect

    Alfonso, F.; Nihoyannopoulos, P.; Stewart, J.; Dickie, S.; Lemery, R.; McKenna, W.J. )

    1990-04-01

    To assess the clinical significance of giant negative T waves in patients with hypertrophic cardiomyopathy from Western nations, clinical, echocardiographic, radionuclide and 48 h electrocardiographic (ECG) monitoring findings were compared in 27 patients with and 56 patients without giant negative T waves. Patients with giant negative T waves were older at diagnosis (43 +/- 15 versus 32 +/- 14 years, p less than 0.005), had greater ECG voltage (SV1 + RV5 = 57 +/- 20 versus 37 +/- 18 mm, p less than 0.001) and had a more vertical frontal plane axis (38.4 +/- 34 versus 13.4 +/- 45 degrees, p less than 0.05). Left ventricular wall thickness on two-dimensional echocardiography was similar at the mitral valve level (mean 16.5 +/- 4 versus 16.6 +/- 3 cm), but was greater at the papillary muscle level (mean 20.7 +/- 5 versus 17.6 +/- 3 mm, p less than 0.01) and apex (mean 23.3 +/- 5 versus 17.3 +/- 3 mm, p less than 0.001) in patients with giant negative T waves. Fewer patients with giant negative T waves had asymmetric septal hypertrophy (12 (44%) of 27 versus 36 (64%) of 56, p = 0.08) or systolic anterior motion of the mitral valve (4 (14%) of 27 versus 25 (45%) of 56, p less than 0.01), whereas left ventricular end-diastolic (44.1 +/- 6 versus 39.6 +/- 5 mm, p = 0.01) and end-systolic dimensions (27.8 +/- 4 versus 24 +/- 6 mm, p less than 0.05) were greater in this group. Nonsustained ventricular tachycardia was seen on ECG monitoring in 21% of patients in both groups.

  8. Abnormal Mitral Valve Dimensions in Pediatric Patients with Hypertrophic Cardiomyopathy.

    PubMed

    Schantz, Daryl; Benson, Lee; Windram, Jonathan; Wong, Derek; Dragulescu, Andreea; Yoo, Shi-Joon; Mertens, Luc; Friedberg, Mark; Al Nafisi, Bahiyah; Grosse-Wortmann, Lars

    2016-04-01

    The hearts of patients with hypertrophic cardiomyopathy (HCM) show structural abnormalities other than isolated wall thickening. Recently, adult HCM patients have been found to have longer mitral valve leaflets than control subjects. The aim of the current study was to assess whether children and adolescents with HCM have similar measureable differences in mitral valve leaflet dimensions when compared to a healthy control group. Clinical and echocardiographic data from 46 children with myocardial hypertrophy and a phenotype and/or genotype consistent with sarcomeric HCM were reviewed. Cardiac magnetic resonance imaging studies were evaluated. The anterior and posterior mitral valve leaflet lengths and myocardial structure were compared to 20 healthy controls. The anterior mitral valve was longer in the HCM group than in the control group (28.4 ± 4.9 vs. 25.2 ± 3.6 mm in control patients, p = 0.013) as was the posterior mitral valve leaflet (16.3 ± 3.0 vs. 13.1 ± 2.3 mm for controls <0.0001). There was no correlation between the resting left ventricular outflow tract gradient and anterior mitral valve leaflet length, nor was the anterior mitral valve leaflet longer in those with systolic anterior motion of the mitral valve compared to those without (28.9 ± 6.1 vs. 28.1 ± 4.5 mm, p = 0.61). Children and adolescents with HCM have abnormally long mitral valve leaflets when compared with healthy control subjects. These abnormalities do not appear to result in, or be due to, obstruction to left ventricular outflow. The mechanism of this mitral valve elongation is not clear but appears to be independent of hemodynamic disturbances.

  9. Dietary copper supplementation reverses hypertrophic cardiomyopathy induced by chronic pressure overload in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sustained pressure overload causes cardiac hypertrophy and the transition to heart failure. We show here that dietary supplementation with physiologically relevant levels of copper (Cu) reverses pre-established hypertrophic cardiomyopathy in the presence of pressure overload induced by ascending aor...

  10. [Right ventricular involvement in hypertrophic cardiomyopathy. A case report and brief review of the literature].

    PubMed

    Comella, Alessandro; Magnacca, Massimo; Gistri, Roberto; Lombardi, Massimo; Neglia, Danilo; Poddighe, Rosa; Pesola, Antonio

    2004-02-01

    A clinical case of non-obstructive hypertrophic cardiomyopathy with involvement of the right ventricle is reported. The patient was a 42-year-old male with symptoms suggesting an effort angina of recent onset. The diagnosis was established by echocardiography, which showed asymmetric hypertrophy of the interventricular septum (20 mm), hypertrophy of the right ventricular free wall, and severe hypertrophy of the septal papillary muscle of the tricuspid valve. The patient underwent a complete diagnostic evaluation, including exercise stress test, Holter monitoring, magnetic resonance, myocardial tomoscintigraphy and complete hemodynamic assessment. Medical treatment with atenolol 50 mg day was started; at 1-year follow-up the patient's clinical conditions are good, with decrease of anginal episodes. The literature review elicits the paucity of information about this condition, despite a frequent involvement of both ventricles in hypertrophic obstructive cardiomyopathy. The case reported shows two atypical aspects: a) the involvement of the right ventricle in non-obstructive hypertrophic cardiomyopathy is anecdotal; b) this pattern of hypertrophy (right ventricular free wall/septal papillary muscle) has never been previously reported. Right ventricular involvement in patients with hypertrophic cardiomyopathy must be carefully investigated, because it may be more frequent than conventionally deemed.

  11. Left Atrial Mechanical Function and Global Strain in Hypertrophic Cardiomyopathy

    PubMed Central

    Yoon, Yeonyee E.; Kim, Hack-Lyoung; Lee, Seung-Pyo; Kim, Hyung-Kwan; Kim, Yong-Jin; Cho, Goo-Yeong; Zo, Joo-Hee; Sohn, Dae-Won

    2016-01-01

    Background Atrial fibrillation is the most common arrhythmia and is associated with adverse outcomes in hypertrophic cardiomyopathy (HCM). Although left atrial (LA) remodeling and dysfunction are known to associate with the development of atrial fibrillation in HCM, the changes of the LA in HCM patients remain unclear. This study aimed to evaluate the changes in LA size and mechanical function in HCM patients compared to control subjects and to determine the characteristics of HCM associated with LA remodeling and dysfunction. Methods Seventy-nine HCM patients (mean age, 54 ± 11 years; 76% were men) were compared to 79 age- and sex-matched controls (mean age, 54 ± 11 years; 76% were men) and 20 young healthy controls (mean age, 33 ± 5 years; 45% were men). The LA diameter, volume, and mechanical function, including global strain (ε), were evaluated by 2D-speckle tracking echocardiography. The phenotype of HCM, maximal left ventricular (LV) wall thickness, LV mass, and presence and extent of late gadolinium enhancement (LGE) were evaluated with cardiac magnetic resonance imaging. Results HCM patients showed increased LA volume index, impaired reservoir function, and decreased LA ε compared to the control subjects. When we divided the HCM group according to a maximal LA volume index (LAVImax) of 38.7 ml/m2 or LA ε of 21%, no significant differences in the HCM phenotype and maximal LV wall thickness were observed for patients with LAVImax >38.7 ml/m2 or LA ε ≤21%. Conversely, the LV mass index was significantly higher both in patients with maximal LA volume index >38.7 ml/m2 and with LA ε ≤21% and was independently associated with LAVImax and LA ε. Although the LGE extent was increased in patients with LA ε ≤21%, it was not independently associated with either LAVImax or LA ε. Conclusions HCM patients showed progressed LA remodeling and dysfunction; the determinant of LA remodeling and dysfunction was LV mass index rather than LV myocardial fibrosis

  12. DDDR pacing for symptomatic patients with hypertrophic obstructive cardiomyopathy

    PubMed Central

    Achterberg, H.J.; Scheffer, M.G.; van Mechelen, R.; Kofflard, M.J.M.; ten Cate, F.J.

    2002-01-01

    Background Hypertrophic obstructive cardiomyopathy (HOCM) is a primary cardiac disorder with a heterogeneous expression. When medical therapy fails in patients with symptomatic HOCM, three additional therapeutic strategies exist: ventricular septal myectomy, alcohol-induced percutaneous transluminal septal myocardial ablation (PTSMA) of the first septal branch of the anterior descending artery and pacemaker implantation. In this paper we present the results of seven patients in whom a dual-chamber pacemaker was implanted to reduce the gradient in the left ventricular outflow tract (LVOT) and to relieve their symptoms. Methods In patients with drug refractory symptomatic HOCM, not eligible for surgery, pacemaker therapy was recommended. Symptomatic HOCM was defined as symptoms of angina and dyspnoea, functional class NYHA 3-4 and a resting LVOT gradient during Doppler echocardiography of more than 2.75 m/s (30 mmHg). In these patients, a dual-chamber pacemaker was implanted with a right ventricular lead positioned in the right ventricular apex and an atrial lead positioned in the right atrial appendage. In all patients the AV setting was programmed between 50 and 100 ms, using Doppler echocardiography to determine the optimal filling and to ensure ventricular capture. Results A statistically significant reduction of the LVOT gradient was observed in all patients. The pre-implantation gradient in the LVOT measured by Doppler echocardiography varied from 3-5.8 m/s with a mean of 4.7±1.1 m/s. The post-implantation gradient varied from 1.4-2.6 m/s with a mean of 1.9±0.4 m/s (p<0.001). Symptomatic improvement was present in all patients. NYHA functional class went from 3-4 (mean 3.1±0.5) pre-implantation to 1-2 mean (1.3±0.4) after implantation (p<0.001). During a mean follow-up of 2.3±1.1 years, the improvement in functional class was maintained. Conclusion Our preliminary results demonstrate that dual-chamber pacing is an effective and safe treatment for

  13. Hypertrophic Obstructive Cardiomyopathy Masked by Tako-Tsubo Syndrome: A Case Report

    PubMed Central

    Daralammori, Y.; El Garhy, M.; Gayed, M. R.; Farah, A.; Lauer, B.; Secknus, M. A.

    2012-01-01

    Introduction. Left ventricular outflow obstruction might be part of the pathophysiological mechanism of Tako-tsubo cardiomyopathy. This obstruction can be masked by Tako-tsubo cardiomyopathy and diagnosed only by followup. Case Presentation. A 70-year-old female presented with Tako-tsubo cardiomyopathy and masked obstructive hypertrophic cardiomyopathy at presentation. Conclusion. Tako-tsubo cardiomyopathy typically presents like an acute MI and is characterized by severe, but transient, regional left ventricular systolic dysfunction. Prompt evaluation of the coronary status is, therefore, mandatory. The prognosis under medical treatment of heart failure symptoms and watchful waiting is favourable. Previous studies showed that LVOT obstruction might be part of the pathophysiological mechanism of TCM. This paper supports this theory. However, TCM may also mask any preexisting LVOT obstruction. PMID:24826256

  14. A new 4D trajectory-based approach unveils abnormal LV revolution dynamics in hypertrophic cardiomyopathy.

    PubMed

    Madeo, Andrea; Piras, Paolo; Re, Federica; Gabriele, Stefano; Nardinocchi, Paola; Teresi, Luciano; Torromeo, Concetta; Chialastri, Claudia; Schiariti, Michele; Giura, Geltrude; Evangelista, Antonietta; Dominici, Tania; Varano, Valerio; Zachara, Elisabetta; Puddu, Paolo Emilio

    2015-01-01

    The assessment of left ventricular shape changes during cardiac revolution may be a new step in clinical cardiology to ease early diagnosis and treatment. To quantify these changes, only point registration was adopted and neither Generalized Procrustes Analysis nor Principal Component Analysis were applied as we did previously to study a group of healthy subjects. Here, we extend to patients affected by hypertrophic cardiomyopathy the original approach and preliminarily include genotype positive/phenotype negative individuals to explore the potential that incumbent pathology might also be detected. Using 3D Speckle Tracking Echocardiography, we recorded left ventricular shape of 48 healthy subjects, 24 patients affected by hypertrophic cardiomyopathy and 3 genotype positive/phenotype negative individuals. We then applied Generalized Procrustes Analysis and Principal Component Analysis and inter-individual differences were cleaned by Parallel Transport performed on the tangent space, along the horizontal geodesic, between the per-subject consensuses and the grand mean. Endocardial and epicardial layers were evaluated separately, different from many ecocardiographic applications. Under a common Principal Component Analysis, we then evaluated left ventricle morphological changes (at both layers) explained by first Principal Component scores. Trajectories' shape and orientation were investigated and contrasted. Logistic regression and Receiver Operating Characteristic curves were used to compare these morphometric indicators with traditional 3D Speckle Tracking Echocardiography global parameters. Geometric morphometrics indicators performed better than 3D Speckle Tracking Echocardiography global parameters in recognizing pathology both in systole and diastole. Genotype positive/phenotype negative individuals clustered with patients affected by hypertrophic cardiomyopathy during diastole, suggesting that incumbent pathology may indeed be foreseen by these methods. Left

  15. Long-Term Survival Following Cardiac Arrest Without Implantable Defibrillator Protection in a Hypertrophic Cardiomyopathy Patient

    PubMed Central

    Cetin, Mustafa; Ucar, Ozgul; Canbay, Alper; Cetin, Zehra Guven; Cicekcioglu, Hulya; Diker, Erdem

    2011-01-01

    Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden cardiac death in young people. Implantable cardioverter defibrillator (ICD) is the optimal therapy in patients with HCM, both for primary or secondary prevention of sudden death. Left ventricular systolic function in HCM is usually normal. However, in few patients, HCM has been reported to progress to a state that is characterized by left ventricular dilation and systolic dysfunction, resembling dilated cardiomyopathy (DCM). Although arrhythmias are common in HCM, advanced or complete atrioventricular block (AV) is very rare. This case report describes a HCM patient who progressed to DCM with advanced AV block and survived 31 years following cardiac arrest without ICD protection.

  16. Evolution of dilated cardiomyopathy (DCM) from idiopathic hypertrophic cardiomyopathy (IHCM) vs. inflammatory dilated cardiomyopathy (DCMi): a rare case of sudden death in an 8-year-old boy.

    PubMed

    Dettmeyer, Reinhard; Schmidt, Peter; Kandolf, Reinhard; Madea, Burkhard

    2004-01-01

    In rare cases, the diagnosis of hypertrophic and dilated cardiomyopathy (DCM) in children was established postmortem. Our case report deals with the sudden and unexpected death of an 8-year-old boy. The postmortem examination revealed non-obstructive hypertrophy with irregular arrangement of muscular fibers, dilatation of the ventricles, endocardial fibrosis, microfocal vacuolization with enlarged hyperchromatic nuclei, and signs of inflammation with interstitial fibrosis. We present an evolution from idiopathic cardiomyopathy to DCM. To some extent, there were morphologic signs of an inflammatory process that first led us to suspect a specific inflammatory DCM.

  17. Renin-angiotensin system gene polymorphisms as potential modifiers of hypertrophic and dilated cardiomyopathy phenotypes.

    PubMed

    Rani, Bindu; Kumar, Amit; Bahl, Ajay; Sharma, Rajni; Prasad, Rishikesh; Khullar, Madhu

    2017-03-01

    The renin-angiotensin (RAS) pathway has an important role in the etiology of heart failure and given the importance of RAS as a therapeutic target in various cardiomyopathies, genetic polymorphisms in the RAS genes may modulate the risk and severity of disease in cardiomyopathy patients. In the present study, we examined the association of RAS pathway gene polymorphisms, angiotensin converting enzyme (ACE), angiotensinogen (AGT), and angiotensin receptor type 1 (AGTR1) with risk and disease severity in Asian Indian idiopathic cardiomyopathy patients. The case-control study was conducted in 400 cardiomyopathy patients diagnosed with HCM, DCM, or restrictive cardiomyopathy (RCM) and 235 healthy controls. Genotyping of patients and controls was done by PCR-RFLP assays. Left ventricular wall thickness and left ventricular ejection fraction were measured by means of M-mode echocardiography. We observed significantly higher prevalence of ACE DD and AGTR1 1166CC genotypes in hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) patients. Also, 235TT genotype of AGT (M235T) was significantly associated with enhanced risk of the disease phenotype in HCM, DCM, and RCM.

  18. Microvascular permeability changes might explain cardiac tamponade after alcohol septal ablation for hypertrophic cardiomyopathy.

    PubMed

    Hsu, Jen-Te; Hsiao, Ju-Feng; Chang, Jung-Jung; Chung, Chang-Min; Chang, Shih-Tai; Pan, Kuo-Li

    2014-04-01

    Various sequelae of alcohol septal ablation for hypertrophic obstructive cardiomyopathy have been reported. Of note, some cases of cardiac tamponade after alcohol septal ablation cannot be well explained. We describe the case of a 78-year-old woman with hypertrophic obstructive cardiomyopathy in whom cardiac tamponade developed one hour after alcohol septal ablation, probably unrelated to mechanical trauma. At that time, we noted a substantial difference in the red blood cell-to-white blood cell ratio between the pericardial effusion (1,957.4) and the peripheral blood (728.3). In addition to presenting the patient's case, we speculate that a possible mechanism for acute tamponade--alcohol-induced changes in microvascular permeability--is a reasonable explanation for cases of alcohol septal ablation that are complicated by otherwise-unexplainable massive pericardial effusions.

  19. Left Atrial trajectory impairment in Hypertrophic Cardiomyopathy disclosed by Geometric Morphometrics and Parallel Transport

    NASA Astrophysics Data System (ADS)

    Piras, Paolo; Torromeo, Concetta; Re, Federica; Evangelista, Antonietta; Gabriele, Stefano; Esposito, Giuseppe; Nardinocchi, Paola; Teresi, Luciano; Madeo, Andrea; Chialastri, Claudia; Schiariti, Michele; Varano, Valerio; Uguccioni, Massimo; Puddu, Paolo E.

    2016-10-01

    The analysis of full Left Atrium (LA) deformation and whole LA deformational trajectory in time has been poorly investigated and, to the best of our knowledge, seldom discussed in patients with Hypertrophic Cardiomyopathy. Therefore, we considered 22 patients with Hypertrophic Cardiomyopathy (HCM) and 46 healthy subjects, investigated them by three–dimensional Speckle Tracking Echocardiography, and studied the derived landmark clouds via Geometric Morphometrics with Parallel Transport. Trajectory shape and trajectory size were different in Controls versus HCM and their classification powers had high AUC (Area Under the Receiving Operator Characteristic Curve) and accuracy. The two trajectories were much different at the transition between LA conduit and booster pump functions. Full shape and deformation analyses with trajectory analysis enabled a straightforward perception of pathophysiological consequences of HCM condition on LA functioning. It might be worthwhile to apply these techniques to look for novel pathophysiological approaches that may better define atrio–ventricular interaction.

  20. The diagnosis of left ventricular outflow tract obstruction in hypertrophic cardiomyopathy.

    PubMed

    Piva e Mattos, Beatriz; Torres, Marco Antonio Rodrigues; Rebelatto, Taiane Francieli; Loreto, Melina Silva de; Scolari, Fernando Luís

    2012-07-01

    Hypertrophic cardiomyopathy is a prevalent genetic disease characterized by left ventricular hypertrophy, presenting dynamic obstruction of outflow tract with subaortic gradient happening at rest in 30% of the cases. It is attributed to the intricate interaction between the anterior mitral leaflet, the interventricular septum and altered flow vectors generated in left ventricle along with changes in outflow tract geometry. Mitral regurgitation in varying degrees is found with or without association with structural deformities of the valve apparatus. The exercise echocardiogram evidences latent obstruction easily induced by exercise in 60 to 75% of non-obstructive forms. The determination of the gradient under this condition must be considered in routine investigation of patients with mild or no obstruction at rest. The evaluation of hypertrophic cardiomyopathy incorporates methods based on the ultrasound image, which, along with MRI, allow recognizing ventricular obstruction generating mechanisms, thus facilitating the diagnosis and management of obstructive and latent obstructive forms.

  1. All That Glitters is not Gold: Apical Hypertrophic Cardiomyopathy Mimicking Acute Coronary Syndrome

    PubMed Central

    Lakshmanadoss, Umashankar; Kulkarni, Abhishek; Balakrishnan, Shobana; Shree, Nidhi; Harjai, Kishore; Jagasia, Dinesh

    2012-01-01

    Hypertrophic cardiomyopathy is characterized by the idiopathic hypertrophy of the left ventricle (and occasionally right ventricle). HCM is an autosomal dominant disease, with variable penetration. In Asian population, apical hypertrophic cardiomyopathy is relatively common (25%). However, this is relatively rare in Caucasian population (0.2%). Patients with HCM, often presents with typical exertional chest pain and shortness of breath. Apical HCM patients tend to have milder symptoms. However, the clinical presentation and electrocardiographic features of Apical HCM often mimic acute coronary syndrome and high index of suspicion is warranted in differentiating this condition. Patients with apical HCM have relatively better prognosis when compare to the other varieties. Here, we are presenting a patient who presented with typical exertional chest pain whose electrocardiographic changes are concerning for acute ischemic changes.

  2. [Functional regulation of genome with peptide bioregulators by hypertrophic cardiomyopathy (by patients and relatives)].

    PubMed

    Dzhokhadze, T A; Buadze, T Zh; Gaĭozishvili, M N; Rogava, M A; Lazhava, T A

    2013-12-01

    In this paper, a comparative study of the functional genome indicators using lymphocyte cultures of patients with hypertrophic cardiomyopathy (HCM) and their first relatives. Studies conducted both in intact cultures and cultures exposed to the influence of peptide - bioregulators Epithalon, Vilon and Livagen. Last (Livagen) tested at separate and joint application with cobalt chloride salt. As indicated according to the results of the analysis, the cells of the individuals with HCM and their first relatives were characterized by higher frequency of spontaneous quantitative - structural disorders in comparison with the cells of healthy individuals. The findings suggest a different effect of bioregulators. The most effective protective action in relation normalization of functional parameters of the genome shows Epithalon for lowering the level of chromosomal instability in patients with hypertrophic cardiomyopathy and relatives of patients with HCM. On the basis of identified protective action Epithalon concludes prospects of its application in the development of preventive measures for individuals at increased risk of morbidity HCM.

  3. An autopsy report of acute myocardial infarction with hypertrophic obstructive cardiomyopathy-like heart.

    PubMed

    Ushikoshi, Hiroaki; Okada, Hideshi; Morishita, Kentaro; Imai, Hajime; Tomita, Hiroyuki; Nawa, Takahide; Suzuki, Kodai; Ikeshoji, Haruka; Kato, Hisaaki; Yoshida, Takahiro; Yoshida, Shozo; Shirai, Kunihiro; Toyoda, Izumi; Hara, Akira; Ogura, Shinji

    2015-01-01

    An 84-year-old woman, who was followed up as hypertrophic obstructive cardiomyopathy (HOCM) in a local hospital, was transferred to our center because of anterior chest pain and diagnosed with acute myocardial infarction (MI). Coronary angiography showed total occlusion of the mid-left anterior descending, and flow was restored after endovascular thrombectomy. An autopsy was performed after she died on hospital day 6. At autopsy, there was no significant stenosis in this vessel and the absence of plaque rupture was confirmed. Likewise, it was unclear asymmetric hypertrophy at autopsy, it could not deny that a sigmoid deformity of the basal septum occurs in elderly patients and can mimic the asymmetric septal hypertrophy of hypertrophic cardiomyopathy. MI was thought to be caused by coronary spasm or squeezing in HOCM-like heart. Therefore, it may be necessary antithrombosis therapy in HOCM-like patients with no history of paroxysmal atrial fibrillation.

  4. Myocardial stunning in hypertrophic cardiomyopathy: recovery predicted by single photon emission computed tomographic thallium-201 scintigraphy

    SciTech Connect

    Fine, D.G.; Clements, I.P.; Callahan, M.J.

    1989-05-01

    A young woman with hypertrophic cardiomyopathy confirmed by echocardiography and cardiac catheterization presented with chest pain and features of a large left ventricular aneurysm. The initial diagnosis was myocardial ischemia with either an evolving or an ancient myocardial infarction. Subsequently, verapamil therapy was associated with complete resolution of the extensive left ventricular wall motion abnormalities, normalization of left ventricular ejection fraction and a minimal myocardial infarction. Normal thallium uptake on single photon emission computed tomographic scintigraphy early in the hospital course predicted myocardial viability in the region of the aneurysm. Thus, orally administered verapamil may reverse spontaneous extensive myocardial ischemia in hypertrophic cardiomyopathy and possibly limit the extent of myocardial infarction in such circumstances.

  5. The myosin mesa and a possible unifying hypothesis for the molecular basis of human hypertrophic cardiomyopathy

    PubMed Central

    Spudich, James A.

    2015-01-01

    No matter how many times one explores the structure of the myosin molecule, there is always something new to discover. Here, I describe the myosin mesa, a structural feature of the motor domain that has the characteristics of a binding domain for another protein, possibly myosin-binding protein C (MyBP-C). Interestingly, many well-known hypertrophic cardiomyopathy (HCM) mutations lie along this surface and may affect the putative interactions proposed here. A potential unifying hypothesis for the molecular basis of human hypertrophic cardiomyopathy is discussed here. It involves increased power output of the cardiac muscle as a result of HCM mutations causing the release of inhibition by myosin binding protein C. PMID:25619247

  6. Left Atrial trajectory impairment in Hypertrophic Cardiomyopathy disclosed by Geometric Morphometrics and Parallel Transport.

    PubMed

    Piras, Paolo; Torromeo, Concetta; Re, Federica; Evangelista, Antonietta; Gabriele, Stefano; Esposito, Giuseppe; Nardinocchi, Paola; Teresi, Luciano; Madeo, Andrea; Chialastri, Claudia; Schiariti, Michele; Varano, Valerio; Uguccioni, Massimo; Puddu, Paolo E

    2016-10-07

    The analysis of full Left Atrium (LA) deformation and whole LA deformational trajectory in time has been poorly investigated and, to the best of our knowledge, seldom discussed in patients with Hypertrophic Cardiomyopathy. Therefore, we considered 22 patients with Hypertrophic Cardiomyopathy (HCM) and 46 healthy subjects, investigated them by three-dimensional Speckle Tracking Echocardiography, and studied the derived landmark clouds via Geometric Morphometrics with Parallel Transport. Trajectory shape and trajectory size were different in Controls versus HCM and their classification powers had high AUC (Area Under the Receiving Operator Characteristic Curve) and accuracy. The two trajectories were much different at the transition between LA conduit and booster pump functions. Full shape and deformation analyses with trajectory analysis enabled a straightforward perception of pathophysiological consequences of HCM condition on LA functioning. It might be worthwhile to apply these techniques to look for novel pathophysiological approaches that may better define atrio-ventricular interaction.

  7. Left Atrial trajectory impairment in Hypertrophic Cardiomyopathy disclosed by Geometric Morphometrics and Parallel Transport

    PubMed Central

    Piras, Paolo; Torromeo, Concetta; Re, Federica; Evangelista, Antonietta; Gabriele, Stefano; Esposito, Giuseppe; Nardinocchi, Paola; Teresi, Luciano; Madeo, Andrea; Chialastri, Claudia; Schiariti, Michele; Varano, Valerio; Uguccioni, Massimo; Puddu, Paolo E.

    2016-01-01

    The analysis of full Left Atrium (LA) deformation and whole LA deformational trajectory in time has been poorly investigated and, to the best of our knowledge, seldom discussed in patients with Hypertrophic Cardiomyopathy. Therefore, we considered 22 patients with Hypertrophic Cardiomyopathy (HCM) and 46 healthy subjects, investigated them by three–dimensional Speckle Tracking Echocardiography, and studied the derived landmark clouds via Geometric Morphometrics with Parallel Transport. Trajectory shape and trajectory size were different in Controls versus HCM and their classification powers had high AUC (Area Under the Receiving Operator Characteristic Curve) and accuracy. The two trajectories were much different at the transition between LA conduit and booster pump functions. Full shape and deformation analyses with trajectory analysis enabled a straightforward perception of pathophysiological consequences of HCM condition on LA functioning. It might be worthwhile to apply these techniques to look for novel pathophysiological approaches that may better define atrio–ventricular interaction. PMID:27713503

  8. The Mitral Valve in Obstructive Hypertrophic Cardiomyopathy: A Test in Context.

    PubMed

    Sherrid, Mark V; Balaram, Sandhya; Kim, Bette; Axel, Leon; Swistel, Daniel G

    2016-04-19

    Mitral valve abnormalities were not part of modern pathological and clinical descriptions of hypertrophic cardiomyopathy in the 1950s, which focused on left ventricular (LV) hypertrophy and myocyte fiber disarray. Although systolic anterior motion (SAM) of the mitral valve was discovered as the cause of LV outflow tract obstruction in the M-mode echocardiography era, in the 1990s structural abnormalities of the mitral valve became appreciated as contributing to SAM pathophysiology. Hypertrophic cardiomyopathy mitral malformations have been identified at all levels. They occur in the leaflets, usually elongating them, and also in the submitral apparatus, with a wide array of malformations of the papillary muscles and chordae, that can be detected by transthoracic and transesophageal echocardiography and by cardiac magnetic resonance. Because they participate fundamentally in the predisposition to SAM, they have increasingly been repaired surgically. This review critically assesses imaging and measurement of mitral abnormalities and discusses their surgical relief.

  9. Hypertrophic Cardiomyopathy (HCM): How Flow Analysis May Drive Medical Management and Surgical Approach

    NASA Astrophysics Data System (ADS)

    Abraham, Theodore P.

    2011-11-01

    Hypertrophic Cardiomyopathy (HCM) is the most common inherited heart disease and occurs in 1 in 500 persons worldwide regardless of race, age and gender. It is the most common cause of sudden death in the young and also causes heart failure and cardiac arrhythmias. The primary anatomic abnormality is thickening of certain walls, or sometimes global thickening of the left or right ventricle. The patterns of thickening along with increased ventricular stiffness lead to suboptimal ventricular filling and inefficient ejection of blood from the ventricle. Treatment for HCM can be medical or surgical. The choice of therapy is driven by the presence and severity of outflow obstruction. Flow analysis could provide sophisticated information about outflow and inflow ventricular dynamics. These flow dynamics features may enable better medical choices and provide information that would allow superior surgical planning. Associate Professor of Medicine & Director, Hypertrophic Cardiomyopathy Clinic

  10. Papillary Thyroid Carcinoma Treated with Radiofrequency Ablation in a Patient with Hypertrophic Cardiomyopathy: A Case Report

    PubMed Central

    Sun, Jianyi; Liu, Xiaosun; Zhang, Qing; Hong, Yanyun; Song, Bin; Teng, Xiaodong

    2016-01-01

    Standard therapy has not been established for thyroid cancer when a thyroidectomy is contraindicated due to systemic disease. Herein, we reported a patient who had hypertrophic cardiomyopathy and papillary thyroid carcinoma treated by radiofrequency ablation because of inability to tolerate a thyroidectomy. Radiofrequency ablation can be used to treat thyroid cancer when surgery is not feasible, although the long-term outcome needs further observation. PMID:27390548

  11. Fatal infantile mitochondrial encephalomyopathy, hypertrophic cardiomyopathy and optic atrophy associated with a homozygous OPA1 mutation

    PubMed Central

    Spiegel, Ronen; Saada, Ann; Flannery, Padraig J; Burté, Florence; Soiferman, Devorah; Khayat, Morad; Eisner, Verónica; Vladovski, Eugene; Taylor, Robert W; Bindoff, Laurence A; Shaag, Avraham; Mandel, Hanna; Schuler-Furman, Ora; Shalev, Stavit A; Elpeleg, Orly; Yu-Wai-Man, Patrick

    2016-01-01

    Background Infantile-onset encephalopathy and hypertrophic cardiomyopathy caused by mitochondrial oxidative phosphorylation defects are genetically heterogeneous with defects involving both the mitochondrial and nuclear genomes. Objective To identify the causative genetic defect in two sisters presenting with lethal infantile encephalopathy, hypertrophic cardiomyopathy and optic atrophy. Methods We describe a comprehensive clinical, biochemical and molecular genetic investigation of two affected siblings from a consanguineous family. Molecular genetic analysis was done by a combined approach involving genome-wide autozygosity mapping and next-generation exome sequencing. Biochemical analysis was done by enzymatic analysis and Western blot. Evidence for mitochondrial DNA (mtDNA) instability was investigated using long-range and real-time PCR assays. Mitochondrial cristae morphology was assessed with transmission electron microscopy. Results Both affected sisters presented with a similar cluster of neurodevelopmental deficits marked by failure to thrive, generalised neuromuscular weakness and optic atrophy. The disease progression was ultimately fatal with severe encephalopathy and hypertrophic cardiomyopathy. Mitochondrial respiratory chain complex activities were globally decreased in skeletal muscle biopsies. They were found to be homozygous for a novel c.1601T>G (p.Leu534Arg) mutation in the OPA1 gene, which resulted in a marked loss of steady-state levels of the native OPA1 protein. We observed severe mtDNA depletion in DNA extracted from the patients’ muscle biopsies. Mitochondrial morphology was consistent with abnormal mitochondrial membrane fusion. Conclusions We have established, for the first time, a causal link between a pathogenic homozygous OPA1 mutation and human disease. The fatal multisystemic manifestations observed further extend the complex phenotype associated with pathogenic OPA1 mutations, in particular the previously unreported association

  12. Vagal enhancement linking abnormal blood pressure response and subendocardial ischemia in hypertrophic cardiomyopathy.

    PubMed

    Kawasaki, Tatsuya; Sugihara, Hiroki

    2014-01-01

    An abnormal blood pressure response to exercise has been reported to be associated with left ventricular subendocardial ischemia in patients with hypertrophic cardiomyopathy (HCM), but the underlying mechanism remains unclear. We report a case of HCM with an abnormal blood pressure response and subendocardial ischemia, in which the analysis of heart rate variability revealed exercise-induced vagal enhancement. The present case highlights the possible mechanism linking abnormal blood pressure response and left ventricular subendocardial ischemia in patients with HCM.

  13. Short term reduction of left ventricular mass in primary hypertrophic cardiomyopathy by octreotide injections.

    PubMed Central

    Günal, A. I.; Işik, A.; Celiker, H.; Eren, O.; Celebi, H.; Günal, S. Y.; Lüleci, C.

    1996-01-01

    Growth factors have been shown to be associated with primary hypertrophic cardiomyopathy. Octreotide, a long acting somatostatin analogue, can prevent the stimulating effect of growth factors and decrease the left ventricular mass in patients with acromegaly. In the light of these results, three patients with primary hypertrophic cardiomyopathy were treated with subcutaneous octreotide (50 micrograms three times a day during the first week and 100 micrograms twice a day for the following three weeks). Initially, two patients were in New York Heart Association class II in and one was in class III. At the end of a four week treatment session all were in class I. There were significant decreases in left ventricular posterior wall thickness, interventricular septum thickness, and left ventricular mass in all three patients. Both left ventricular end diastolic and end systolic diameters had increased in all of the patients at the end of the fourth week. Two of three patients showed improved diastolic filling: their hyperdynamic systolic performance returned to normal. No side effects were observed during octreotide treatment. The considerable improvement obtained with the short term octreotide treatment in patients with primary hypertrophic cardiomyopathy seems promising. PMID:8944587

  14. Benazepril and subclinical feline hypertrophic cardiomyopathy: A prospective, blinded, controlled study

    PubMed Central

    Di Fruscia, Rocky

    2006-01-01

    Abstract Twenty-one cats with hypertrophic cardiomyopathy were enrolled in this study to determine if the administration of benazepril (0.5 mg/kg body weight [BW], PO, q24h) to cats with subclinical hypertrophic cardiomyopathy improves cardiac diastolic function and reverses left ventricular hypertrophy when compared with diltiazem controlled delivery (CD) (10 mg/kg BW, PO, q24h). Cats were evaluated at day 0 and after 3 and 6 months of therapy. In the benazepril group (n = 11), the diastolic transmitral flow of the E and A waves ratio (E/A ratio) increased significantly between 0 and 6 months (P = 0.009) and the thickness of the left ventricular free wall in systole (LVFWs) decreased significantly between 0 and 3 months (P = 0.04). In the diltiazem CD group (n = 5), none of the parameters varied significantly throughout the study. There was no difference between the benazepril and the diltiazem CD group throughout the study. Therefore, the variations observed for the E/A ratio and the LVFWs may have been incidental. Further studies will be needed to establish the role of benazepril in subclinical hypertrophic cardiomyopathy in cat. PMID:16734369

  15. Mitochondrial ND5 12338T>C variant is associated with maternally inherited hypertrophic cardiomyopathy in a Chinese pedigree.

    PubMed

    Liu, Zhong; Song, Yanrui; Gu, Shulian; He, Xiangyu; Zhu, Xiaoyu; Shen, Yaoyao; Wu, Bifeng; Wang, Wei; Li, Shishi; Jiang, Pingping; Lu, Jianhua; Huang, Wendong; Yan, Qingfeng

    2012-09-15

    Hypertrophic cardiomyopathy is a primary disorder characterized by asymmetric thickening of the septum and left ventricular wall, which affects 1 in 500 individuals in the general population. Mutations in mitochondrial DNA have been found to be one of the most important causes of hypertrophic cardiomyopathy. Here we report the clinical, genetic and molecular characterization of a Han Chinese family with a likely maternally transmitted hypertrophic cardiomyopathy. Four (2 men/2 women) of 5 matrilineal relatives in this 3-generation family exhibited the variable severity and age at onset of 44 to 79 years old. Sequence analysis of the entire mitochondrial DNA in this pedigree identified the known homoplasmic ND5 12338T>C variant. This mitochondrial DNA haplogroup belongs to the Eastern Asian F2a. The 12338T>C variant, highly evolutionarily conserved, resulted in the replacement of the translation initiating methionine with a threonine, shortening the ND5 polypeptide by 2 amino acids. The occurrence of ND5 12338T>C variant exclusively in maternal members of this Chinese family suggested that the 12338T>C variant is associated with maternally inherited hypertrophic cardiomyopathy. Our findings will provide theoretical basis for genetic counseling of maternally inherited hypertrophic cardiomyopathy.

  16. Cardiac beta-myosin heavy chain defects in two families with non-compaction cardiomyopathy: linking non-compaction to hypertrophic, restrictive, and dilated cardiomyopathies.

    PubMed

    Hoedemaekers, Yvonne M; Caliskan, Kadir; Majoor-Krakauer, Danielle; van de Laar, Ingrid; Michels, Michelle; Witsenburg, Maarten; ten Cate, Folkert J; Simoons, Maarten L; Dooijes, Dennis

    2007-11-01

    Cardiomyopathies are classified according to distinct morphological characteristics. They occur relatively frequent and are an important cause of mortality and morbidity. Isolated ventricular non-compaction or non-compaction cardiomyopathy (NCCM) is characterized by an excessively thickened endocardial layer with deep intertrabecular recesses, reminiscent of the myocardium during early embryogenesis. Aims Autosomal-dominant as well as X-linked inheritance for NCCM has been described and several loci have been associated with the disease. Nevertheless, a major genetic cause for familial NCCM remains to be identified. Methods and Results We describe, in two separate autosomal-dominant NCCM families, the identification of mutations in the sarcomeric cardiac beta-myosin heavy chain gene (MYH7), known to be associated with hypertrophic cardiomyopathy (HCM), restricted cardiomyopathy (RCM), and dilated cardiomyopathy (DCM). Conclusion These results confirm the genetic heterogeneity of NCCM and suggest that the molecular classification of cardiomyopathies includes an MYH7-associated spectrum of NCCM with HCM, RCM, and DCM.

  17. "Sawfish" systolic narrowing of the left anterior descending coronary artery: an angiographic sign of hypertrophic cardiomyopathy.

    PubMed

    Brugada, P; Bär, F W; de Zwaan, C; Roy, D; Green, M; Wellens, H J

    1982-10-01

    The morphologic characteristics at coronary arteriography of systolic narrowing of the left anterior descending coronary artery (LAD) were evaluated in 14 patients. Six patients had systolic narrowing of the LAD not associated with other cardiac abnormalities (group A) and eight patients had systolic narrowing of the LAD associated with hypertrophic cardiomyopathy (group B). Patients in group A showed a smooth and progressive constriction of the vessel up to the point of maximal stenosis, giving it a "rat-tail" appearance. There was no systolic narrowing of septal branches or of other epicardial vessels in this group. In patients of group B, systolic narrowing of the LAD had a "saw-fish" appearance. Seven patients had systolic narrowing of the septal branches, and five had systolic narrowing of other epicardial vessels. These data indicate that systolic narrowing of the LAD in patients with hypertrophic cardiomyopathy differs angiographically from systolic narrowing due to an intramural course of a part of the vessel (as in group A patients). We postulate that in patients with hypertropic cardiomyopathy, fiber hypertrophy and disarray in the vicinity of the coronary vessels is responsible for the morphology and the widespread distribution of systolic narrowing.

  18. Myocardial edema in Takotsubo syndrome mimicking apical hypertrophic cardiomyopathy: An insight into diagnosis by cardiovascular magnetic resonance.

    PubMed

    Izgi, Cemil; Ray, Sanjoy; Nyktari, Evangelia; Alpendurada, Francisco; Lyon, Alexander R; Rathore, Sudhir; Baksi, Arun John

    2015-01-01

    Myocardial edema is one of the characteristic features in the pathogenesis of Takotsubo syndrome. We report a middle aged man who presented with typical clinical and echocardiographic features of apical variant of Takotsubo syndrome. However, a cardiovascular magnetic resonance study performed 10 days after presentation did not show any apical 'ballooning' but revealed features of an apical hypertrophic cardiomyopathy on cine images. Tissue characterization with T2 weighted images proved severe edema as the cause of significantly increased apical wall thickness. A follow-up cardiovascular magnetic resonance study was performed 5 months later which showed that edema, wall thickening and the appearance of apical hypertrophic cardiomyopathy all resolved, confirming Takotsubo syndrome as the cause of the initial appearance. As the affected myocardium most commonly involves the apical segments, an edema induced increase in apical wall thickness may lead to appearances of an apical hypertrophic cardiomyopathy rather than apical ballooning in the acute to subacute phase of Takotsubo syndrome.

  19. A small-molecule inhibitor of sarcomere contractility suppresses hypertrophic cardiomyopathy in mice.

    PubMed

    Green, Eric M; Wakimoto, Hiroko; Anderson, Robert L; Evanchik, Marc J; Gorham, Joshua M; Harrison, Brooke C; Henze, Marcus; Kawas, Raja; Oslob, Johan D; Rodriguez, Hector M; Song, Yonghong; Wan, William; Leinwand, Leslie A; Spudich, James A; McDowell, Robert S; Seidman, J G; Seidman, Christine E

    2016-02-05

    Hypertrophic cardiomyopathy (HCM) is an inherited disease of heart muscle that can be caused by mutations in sarcomere proteins. Clinical diagnosis depends on an abnormal thickening of the heart, but the earliest signs of disease are hyperdynamic contraction and impaired relaxation. Whereas some in vitro studies of power generation by mutant and wild-type sarcomere proteins are consistent with mutant sarcomeres exhibiting enhanced contractile power, others are not. We identified a small molecule, MYK-461, that reduces contractility by decreasing the adenosine triphosphatase activity of the cardiac myosin heavy chain. Here we demonstrate that early, chronic administration of MYK-461 suppresses the development of ventricular hypertrophy, cardiomyocyte disarray, and myocardial fibrosis and attenuates hypertrophic and profibrotic gene expression in mice harboring heterozygous human mutations in the myosin heavy chain. These data indicate that hyperdynamic contraction is essential for HCM pathobiology and that inhibitors of sarcomere contraction may be a valuable therapeutic approach for HCM.

  20. A small-molecule inhibitor of sarcomere contractility suppresses hypertrophic cardiomyopathy in mice

    PubMed Central

    Green, Eric M.; Wakimoto, Hiroko; Anderson, Robert L.; Evanchik, Marc J.; Gorham, Joshua M.; Harrison, Brooke C.; Henze, Marcus; Kawas, Raja; Oslob, Johan D.; Rodriguez, Hector M.; Song, Yonghong; Wan, William; Leinwand, Leslie A.; Spudich, James A.; McDowell, Robert S.; Seidman, J. G.; Seidman, Christine E.

    2016-01-01

    Hypertrophic cardiomyopathy (HCM) is an inherited disease of heart muscle that can be caused by mutations in sarcomere proteins. Clinical diagnosis depends on an abnormal thickening of the heart, but the earliest signs of disease are hyperdynamic contraction and impaired relaxation. Whereas some in vitro studies of power generation by mutant and wild-type sarcomere proteins are consistent with mutant sarcomeres exhibiting enhanced contractile power, others are not. We identified a small molecule, MYK-461, that reduces contractility by decreasing the adenosine triphosphatase activity of the cardiac myosin heavy chain. Here we demonstrate that early, chronic administration of MYK-461 suppresses the development of ventricular hypertrophy, cardiomyocyte disarray, and myocardial fibrosis and attenuates hypertrophic and profibrotic gene expression in mice harboring heterozygous human mutations in the myosin heavy chain. These data indicate that hyperdynamic contraction is essential for HCM pathobiology and that inhibitors of sarcomere contraction may be a valuable therapeutic approach for HCM. PMID:26912705

  1. Myocardial metabolic, hemodynamic, and electrocardiographic significance of reversible thallium-201 abnormalities in hypertrophic cardiomyopathy

    SciTech Connect

    Cannon, R.O. 3d.; Dilsizian, V.; O'Gara, P.T.; Udelson, J.E.; Schenke, W.H.; Quyyumi, A.; Fananapazir, L.; Bonow, R.O. )

    1991-05-01

    Exercise-induced abnormalities during thallium-201 scintigraphy that normalize at rest frequently occur in patients with hypertrophic cardiomyopathy. However, it is not known whether these abnormalities are indicative of myocardial ischemia. Fifty patients with hypertrophic cardiomyopathy underwent exercise {sup 201}Tl scintigraphy and, during the same week, measurement of myocardial lactate metabolism and hemodynamics during pacing stress. Thirty-seven patients (74%) had one or more {sup 201}Tl abnormalities that completely normalized after 3 hours of rest; 26 had regional myocardial {sup 201}Tl defects, and 26 had apparent left ventricular cavity dilatation with exercise, with 15 having coexistence of these abnormal findings. Of the 37 patients with reversible {sup 201}Tl abnormalities, 27 (73%) had metabolic evidence of myocardial ischemia during rapid atrial pacing compared with four of 13 patients (31%) with normal {sup 201}Tl scans (p less than 0.01). Eleven patients had apparent cavity dilatation as their only {sup 201}Tl abnormality; their mean postpacing left ventricular end-diastolic pressure was significantly higher than that of the 13 patients with normal {sup 201}Tl studies (33 +/- 5 versus 21 +/- 10 mm Hg, p less than 0.001). There was no correlation between the angiographic presence of systolic septal or epicardial coronary arterial compression and the presence or distribution of {sup 201}Tl abnormalities. Patients with ischemic ST segment responses to exercise had an 80% prevalence rate of reversible {sup 201}Tl abnormalities and a 70% prevalence rate of pacing-induced ischemia. However, 69% of patients with nonischemic ST segment responses had reversible {sup 201}Tl abnormalities, and 55% had pacing-induced ischemia. Reversible {sup 201}Tl abnormalities during exercise stress are markers of myocardial ischemia in hypertrophic cardiomyopathy and most likely identify relatively underperfused myocardium.

  2. Nonobstructive Hypertrophic Cardiomyopathy Out of the Shadows: Known from the Beginning but Largely Ignored … Until Now.

    PubMed

    Maron, Barry J; Rowin, Ethan J; Maron, Martin S; Braunwald, Eugene

    2017-02-01

    Hypertrophic cardiomyopathy was first recognized as a disease of obstruction to left ventricular outflow, hence, its early names and acronyms such as idiopathic hypertrophic subaortic obstruction. The nonobstructive subset of patients, incapable of developing mechanical impedance to left ventricular outflow at rest or with physiologic exercise, was initially recognized by the Braunwald group at the National Institutes of Health >50 years ago in the preimaging era, and is now recognized as comprising about one-third of hypertrophic cardiomyopathy patients. Nevertheless, until recently, and for 25 years, this substantial patient subset has been largely ignored and incompletely understood in terms of its clinical significance and consequences. However, the newfound interest in nonobstructive hypertrophic cardiomyopathy with recent cohort data permits more robust clarity of this subset, as well as the overall disease spectrum. As a group, patients with nonobstructive disease experience a largely stable clinical course at relatively low risk for progressive heart failure symptoms to New York Heart Association class III/IV in (90%). On the other hand, there is a small but important subgroup of 10% at risk for developing drug-refractory advanced heart failure sufficient to justify consideration for heart transplant as the only definitive treatment option. This recognition closes a significant gap in understanding the natural history of hypertrophic cardiomyopathy, also underscoring that the disease is not uniformly grim but instead consistent with extended longevity, thereby providing many patients with a measure of reassurance.

  3. Hypertrophic Cardiomyopathy After a Single Dose of Dexamethasone in a Preterm Infant.

    PubMed

    Kale, Yusuf; Aydemir, Ozge; Ceylan, Ozben; Bas, Ahmet Yagmur; Demirel, Nihal

    2015-08-01

    Dexamethasone is widely used in preterm infants with severe pulmonary disease. Hypertrophic cardiomyopathy (HCM) is a transient side effect observed after multiple doses of dexamethasone. We report a preterm infant with myocardial hypertrophy after a single dose of dexamethasone (0.5 mg/kg) used to treat laryngeal edema secondary to prolonged intubation. A benign course was observed without left ventricular outflow tract obstruction and with recovery within 4 weeks. Myocardial effects of dexamethasone may be independent of dose and duration of treatment. The risk/benefit ratio must be carefully considered before using even a single dose of dexamethasone in preterm infants.

  4. Hypertrophic Cardiomyopathy due to Mitochondrial Disease: Prenatal Diagnosis, Management, and Outcome

    PubMed Central

    García-Díaz, Lutgardo; Coserria, Félix; Antiñolo, Guillermo

    2013-01-01

    A case of prenatally diagnosed fetal hypertrophic cardiomyopathy is reported. The mother was referred to our department at 37 weeks' gestation because of suspected congenital heart disease. Prenatal echocardiography showed biventricular hypertrophy and pericardial effusion, without additional abnormalities. Postnatal echocardiography confirmed prenatal diagnosis. Neonatal EKG showed biventricular hypertrophy and Wolff-Parkinson-White syndrome. Skeletal muscle biopsy was consistent with mitochondrial oxidative phosphorylation defect involving a combined defect of respiratory complexes I and IV. Echocardiographic followup during the first year of life showed progressive regression of hypertrophy and evolution to left ventricular myocardial noncompaction. PMID:23346437

  5. Visualization of myocardial perfusion after percutaneous myocardial septal ablation for hypertrophic cardiomyopathy using superharmonic imaging.

    PubMed

    Ten Cate, Folkert J; Bouakaz, Ayache; Krenning, Boudewijn; Vletter, Wim; de Jong, Nico

    2003-04-01

    Harmonic imaging is used for detection of ultrasound contrast agents in myocardial perfusion studies. However, harmonic imaging has limitations because of the presence of tissue harmonics, which results in less specificity and sensitivity, thus, lower contrast-to-tissue ratio. We describe a clinical example using superharmonic imaging. This technique detects the third, fourth, and fifth harmonics. These harmonics are not created in tissue, resulting, hence, in a high contrast-to-tissue ratio. After myocardial alcohol ablation for hypertrophic cardiomyopathy areas of nontreated and treated myocardium, normal and low flow could be visualized with superharmonic imaging.

  6. Furthering the link between the sarcomere and primary cardiomyopathies: restrictive cardiomyopathy associated with multiple mutations in genes previously associated with hypertrophic or dilated cardiomyopathy.

    PubMed

    Caleshu, Colleen; Sakhuja, Rahul; Nussbaum, Robert L; Schiller, Nelson B; Ursell, Philip C; Eng, Celeste; De Marco, Teresa; McGlothlin, Dana; Burchard, Esteban González; Rame, J Eduardo

    2011-09-01

    Mutations in genes that encode components of the sarcomere are well established as the cause of hypertrophic and dilated cardiomyopathies. Sarcomere genes, however, are increasingly being associated with other cardiomyopathies. One phenotype more recently recognized as a disease of the sarcomere is restrictive cardiomyopathy (RCM). We report on two patients with RCM associated with multiple mutations in sarcomere genes not previously associated with RCM. Patient 1 presented with NYHA Class III/IV heart failure at 22 years of age. She was diagnosed with RCM and advanced heart failure requiring heart transplantation. Sequencing of sarcomere genes revealed previously reported homozygous p.Glu143Lys mutations in MYL3, and a novel heterozygous p.Gly57Glu mutation in MYL2. The patient's mother is a double heterozygote for these mutations, with no evidence of cardiomyopathy. Patient 2 presented at 35 years of age with volume overload while hospitalized for oophorectomy. She was diagnosed with RCM and is being evaluated for heart transplantation. Sarcomere gene sequencing identified homozygous p.Asn279His mutations in TPM1. The patient's parents are consanguineous and confirmed heterozygotes. Her father was diagnosed with HCM at 42 years of age. This is the first report of mutations in TPM1, MYL3, and MYL2 associated with primary, non-hypertrophied RCM. The association of more sarcomere genes with RCM provides further evidence that mutations in the various sarcomere genes can cause different cardiomyopathy phenotypes. These cases also contribute to the growing body of evidence that multiple mutations have an additive effect on the severity of cardiomyopathies.

  7. Nrf2 deficiency prevents reductive stress-induced hypertrophic cardiomyopathy

    PubMed Central

    Kannan, Sankaranarayanan; Muthusamy, Vasanthi R.; Whitehead, Kevin J.; Wang, Li; Gomes, Aldrin V.; Litwin, Sheldon E.; Kensler, Thomas W.; Abel, E. Dale; Hoidal, John R.; Rajasekaran, Namakkal S.

    2013-01-01

    Aims Mutant protein aggregation (PA) cardiomyopathy (MPAC) is characterized by reductive stress (RS), PA (of chaperones and cytoskeletal components), and ventricular dysfunction in transgenic mice expressing human mutant CryAB (hmCryAB). Sustained activation of nuclear erythroid-2 like factor-2 (Nrf2) causes RS, which contributes to proteotoxic cardiac disease. The goals of this pre-clinical study were to (i) investigate whether disrupting Nrf2-antioxidant signalling prevents RS and rescues redox homeostasis in hearts expressing the mutant chaperone and (ii) elucidate mechanisms that could delay proteotoxic cardiac disease. Methods and results Non-transgenic (NTG), transgenic (TG) with MPAC and MPAC-TG:Nrf2-deficient (Nrf2-def) mice were used in this study. The effects of Nrf2 diminution (Nrf2±) on RS mediated MPAC in TG mice were assessed at 6–7 and 10 months of age. The diminution of Nrf2 prevented RS and prolonged the survival of TG mice (∼50 weeks) by an additional 20–25 weeks. The TG:Nrf2-def mice did not exhibit cardiac hypertrophy at even 60 weeks, while the MPAC-TG mice developed pathological hypertrophy and heart failure starting at 24–28 weeks of age. Aggregation of cardiac proteins was significantly reduced in TG:Nrf2-def when compared with TG mice at 7 months. Preventing RS and maintaining redox homeostasis in the TG:Nrf2-def mice ameliorated PA, leading to decreased ubiquitination of proteins. Conclusion Nrf2 deficiency rescues redox homeostasis, which reduces aggregation of mutant proteins, thereby delaying the proteotoxic pathological cardiac remodelling caused by RS and toxic protein aggregates. PMID:23761402

  8. Color-coded Doppler imaging of systolic flow patterns in hypertrophic cardiomyopathy.

    PubMed

    Tencate, F J; Mayala, A P; Vletter, W B; Roelandt, J

    1985-01-01

    We studied 11 patients with hypertrophic cardiomyopathy by color Doppler echocardiography (Group I: 6 patients with outflow obstruction, and Group II: 5 patients without outflow obstruction) to assess systolic structure and function as observed by cross-sectional echocardiography in relation to the flow dynamics. The structure and function included systolic anterior motion of mitral valve (SAM), midsystolic aortic valve closure (AoC), systolic cavity obliteration and the presence and timing of mitral incompetence. Their occurrence and timing was related to presence of aortic systolic flow and presence of turbulence. While all patients in Group I had SAM and turbulence, none of the patients in Group II had SAM nor turbulence. Early mitral incompetence appearing before SAM and turbulence, occurred in all patients of Group I and in none of Group II. Midsystolic aortic valve closure was only present in Group I and blood flow was unilaterally directed so that only 60% of aortic cross-sectional area showed blood flow. We conclude that mitral incompetence in hypertrophic cardiomyopathy in early systole is common when outflow gradient is present and is independent of mitral incompetence of mid- and late systole. During SAM, turbulence in the subaortic area and mid and late mitral incompetence occurred simultaneously. The midsystolic aortic valve closure was related to the unilaterally directed blood flow through the aortic cross-sectional area.

  9. Supraventricular tachycardia in a patient with Lown-Ganong-Levine syndrome associated with apical hypertrophic cardiomyopathy.

    PubMed

    Hayano, M; Imamura, Y; Tsuruta, M; Inoue, J; Nakashima, H; Fukuyama, K; Eguchi, Y; Tsuji, S; Matsuo, S; Yano, K

    1988-03-01

    Electrophysiologic study of a 55-year-old patient with Lown-Ganong-Levine syndrome associated with apical hypertrophic cardiomyopathy is reported. The patient had a history of recurrent attacks of tachyarrhythmia and his electrocardiogram showed a short P-R interval (0.10 sec) with narrow QRS complex and left ventricular hypertrophy with giant negative T waves. His cineangiogram showed severe apical hypertrophy. An electrophysiologic study was performed. The results of programmed atrial pacing show the existence of the dual A-V nodal pathways. The A-H interval at rapid atrial pacing increased maximally by 103 msec. Atrial stimulation could depolarize parts of the atrium without altering the supraventricular tachycardia. These findings suggested that preferential rapidly conducting A-V nodal and intranodal reentry are the responsible mechanisms in this reciprocating tachycardia. We conclude that the short P-R interval was due to intranodal reentry through the dual A-V nodal pathways. To our knowledge, a case of Lown-Ganong-Levine syndrome with apical hypertrophic cardiomyopathy has not been previously described in the literature.

  10. The clinical features, outcomes and genetic characteristics of hypertrophic cardiomyopathy patients with severe right ventricular hypertrophy

    PubMed Central

    Guo, Xiying; Fan, Chaomei; Tian, Lei; Zhang, Xiuling; Zhao, Xing; Wang, Fengqi; Zhu, Hongguang; Lin, Aiqing; Wu, Xia; Li, Yishi

    2017-01-01

    Introduction Severe right ventricular hypertrophy (SRVH) is a rare phenotype in hypertrophic cardiomyopathy (HCM) for which limited information is available. This study was undertaken to investigate the clinical, prognostic and genetic characteristics of HCM patients with SRVH. Methods HCM with SRVH was defined as HCM with a maximum right ventricular wall thickness ≥10 mm. Whole-genome sequencing (WGS) was performed in HCM patients with SRVH. Multivariate Cox proportional hazards regression models were used to identify risk factors for cardiac death and events in HCM with SRVH. Patients with apical hypertrophic cardiomyopathy (ApHCM) were selected as a comparison group. The clinical features and outcomes of 34 HCM patients with SRVH and 273 ApHCM patients were compared. Results Compared with the ApHCM group, the HCM with SRVH group included younger patients and a higher proportion of female patients and also displayed higher cardiovascular morbidity and mortality. The multivariate Cox proportional hazards regression models identified 2 independent predictors of cardiovascular death in HCM patients with SRVH, a New York Heart Association class ≥III (hazard ratio [HR] = 8.7, 95% confidence interval (CI): 1.43-52.87, p = 0.019) and an age at the time of HCM diagnosis ≤18 (HR = 5.5, 95% CI: 1.24-28.36, p = 0.026). Among the 11 HCM patients with SRVH who underwent WGS, 10 (90.9%) were identified as carriers of at least one specific sarcomere gene mutation. MYH7 and TTN mutations were the most common sarcomere mutations noted in this study. Two or more HCM-related gene mutations were observed in 9 (82%) patients, and mutations in either other cardiomyopathy-related genes or ion-channel disease-related genes were found in 8 (73%) patients. Conclusions HCM patients with SRVH were characterized by poor clinical outcomes and the presentation of multiple gene mutations. PMID:28323875

  11. [Mode of splitting of the second heart sound in patients with hypertrophic cardiomyopathy].

    PubMed

    Fukuda, N; Oki, T; Sakai, H; Asai, M; Ohshima, C; Kusaka, Y; Tominaga, T; Murao, A; Niki, T; Mori, H

    1983-06-01

    Mode of the splitting of the second heart sound ( IIs ) and left ventricular systolic time intervals (STIs) in patients (pts) with hypertrophic cardiomyopathy were compared with those in hypertension (HT) with the global hypertrophy of the left ventricular wall. Forty-seven pts with hypertrophic cardiomyopathy [non-obstructive type (HCM, 30 pts), obstructive type (HOCM, 17 pts)] and 21 pts with HT were studied. The pts with HCM were classified as septal hypertrophic type (19 pts) and apical hypertrophic type (11 pts) on the basis of the echocardiographic findings. The pts with HOCM were classified as resting type (13 pts) and latent type (provoked by amyl nitrite: 4 pts) on the basis of the obstructive sign at rest. Mode of the splitting of the IIs : a) The pts with HCM showed a wide splitting of the IIs . The mean split interval during held expiration (IIA-IIP) was 41.0 +/- 9.9 msec. Twenty pts (67%) showed abnormal respiratory splitting. The mean IIA-IIP interval in septal hypertrophic type (45.3 +/- 9.0 msec) was significantly wider than that in apical hypertrophic type (33.6 +/- 6.7 msec) (p less than 0.05). There was a positive correlation between IIA-IIP interval and the thickness of the upper portion of the interventricular septum (r = 0.63). b) Nine out of 13 pts with resting type of HOCM showed a paradoxical (reversed) splitting with a mean IIA-IIP interval of -23.8 +/- 24.4 msec. On the other hand, pts with latent type showed a wide splitting similar to HCM with a mean IIA-IIP interval of 35.0 +/- 7.1 msec. c) The pts with HT showed a single IIs or physiological splitting. The mean IIA-IIP interval was 14.5 +/- 9.3 msec, which was significantly decreased than that of normals or the pts with HCM (p less than 0.01). Left ventricular systolic time intervals: a) The pts with an either type of HCM showed a short corrected left ventricular electromechanical systole [(Q-IIA)c] due to the shortening of the corrected left ventricular ejection time (LVETc). b) The

  12. Cardiac CT angiography in the emergency room: Apical hypertrophic cardiomyopathy presenting as acute coronary syndrome.

    PubMed

    Turner, Michael C; Kerut, Edmund K; Mckinnie, James; Davis, Michael; Hinton, Christine

    2017-03-07

    A 59-year-old male presented to the emergency room with symptoms of chest tightness and palpitations. Following conversion of atrial fibrillation to sinus rhythm, he had deep symmetrical T-wave changes on his electrocardiogram. Symptoms resolved almost immediately, and his initial troponin was negative. He underwent cardiac CT angiography utilizing an emergency room triage protocol which resulted in a diagnosis of nonobstructive coronary artery disease and apical hypertrophic cardiomyopathy. Following a hospital stay of less than 24 hours, he was discharged to outpatient follow-up on medical management and has remained asymptomatic over 6 months. This case presentation illustrates an example of the diversity of pathology that presents in emergency rooms with symptoms consistent with acute coronary syndrome.

  13. MicroRNAs Based Therapy of Hypertrophic Cardiomyopathy: The Road Traveled So Far

    PubMed Central

    Roma-Rodrigues, Catarina; Raposo, Luís R.; Fernandes, Alexandra R.

    2015-01-01

    Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease characterized by variable expressivity, age penetrance, and a high heterogeneity. The transcriptional profile (miRNAs, mRNAs), epigenetic modifications, and posttranslational modifications seem to be highly relevant for the onset of the disease. miRNAs, small noncoding RNAs with 22 nucleotides, have been implicated in the regulation of cardiomyocyte function, being differentially expressed in several heart diseases, including HCM. Moreover, a different miRNA expression profile in the various stages of HCM development is also observed. This review summarizes the current knowledge of the profile of miRNAs characteristic of asymptomatic to overt HCM patients, discussing alongside their potential use for diagnosis and therapy. Indeed, the stability and specificity of miRNAs make them suitable targets for use as biomarkers for diagnosis and prognosis and as therapeutical targets. PMID:26504850

  14. Narrative review: harnessing molecular genetics for the diagnosis and management of hypertrophic cardiomyopathy.

    PubMed

    Wang, Libin; Seidman, Jonathan G; Seidman, Christine E

    2010-04-20

    Unexplained cardiac hypertrophy, the diagnostic criterion for hypertrophic cardiomyopathy (HCM), occurs in 1 in 500 adults. Insights into the genetic cause and molecular pathophysiology of HCM are reshaping clinical paradigms for diagnosis and treatment of this common myocardial disorder. Human genetic studies have established that dominant mutations in the proteins that make up the contractile apparatus (the sarcomere) cause HCM. With the current availability of clinical gene-based diagnostics, pathogenic mutations in affected patients can be defined, which can suggest a clinical course and allow definitive preclinical identification of family members at risk for HCM. Genetic discoveries have also fostered mechanistic investigations in model organisms that are engineered to carry human HCM mutations. Novel therapeutic targets have emerged from these fundamental studies and are currently under clinical assessment in humans. The combination of contemporary gene-based diagnosis with new strategies to attenuate disease development and progression is changing the natural history of lifelong cardiac symptoms, arrhythmias, and heart failure from HCM.

  15. Isolated papillary muscle hypertrophy: A gap in our knowledge of hypertrophic cardiomyopathy?

    PubMed

    Ferreira, Catarina; Delgado, Carlos; Vázquez, María; Trinidad, Carmen; Vilar, Manuel

    2014-06-01

    Increased thickness of left ventricular walls is the predominant characteristic and one of the diagnostic criteria of hypertrophic cardiomyopathy (HCM). This case illustrates an uncommon but important finding of isolated hypertrophy of the papillary muscles (PMs), observed in a young woman in whom an abnormal electrocardiogram was initially detected. During the investigation isolated PM hypertrophy was identified. The structural characteristics of the PMs have received scant attention in this setting and there is little information in the literature on this entity, whose real prevalence and clinical significance remain to be determined. The available information relates solitary PM hypertrophy with an early form or a different pattern of HCM. In this case PM hypertrophy was only detected due to the finding of an abnormal electrocardiogram, which prompted further diagnostic tests and a search for possible etiologies.

  16. Cardiac Magnetic Resonance and Computed Tomography in Hypertrophic Cardiomyopathy: an Update

    PubMed Central

    de Oliveira, Diogo Costa Leandro; Assunção, Fernanda Boldrini; dos Santos, Alair Agusto Sarmet Moreira Damas; Nacif, Marcelo Souto

    2016-01-01

    Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease and represents the main cause of sudden death in young patients. Cardiac magnetic resonance (CMR) and cardiac computed tomography (CCT) are noninvasive imaging methods with high sensitivity and specificity, useful for the establishment of diagnosis and prognosis of HCM, and for the screening of patients with subclinical phenotypes. The improvement of image analysis by CMR and CCT offers the potential to promote interventions aiming at stopping the natural course of the disease. This study aims to describe the role of RCM and CCT in the diagnosis and prognosis of HCM, and how these methods can be used in the management of these patients. PMID:27305111

  17. Hypertrophic cardiomyopathy in daily practice: an introduction on diagnosis, prognosis and treatment

    PubMed Central

    van der Lee, C.; Kofflard, M. J.; Geleijnse, M.L.; ten Cate, F.J.

    2005-01-01

    Hypertrophic cardiomyopathy (HCM) is a complex, inherited cardiac disease that has been subject to intense investigation since it was first described in 1957. Over the past 40 years, understanding has evolved regarding the diagnosis, prognosis and treatment of HCM. Analyses of HCM populations from nonreferral centres have refined the insights into the natural history and the occurrence of sudden cardiac death, which is the most devastating component of its natural history. Therapeutic strategies are diverse and may vary during the course of the disease. Optimal therapy depends on symptoms, haemodynamic findings and the presence of risk factors for sudden cardiac death. At present, invasive therapy for patients with obstructive HCM and drug-refractory symptoms includes surgery or percutaneous transluminal septal myocardial ablation. This report summarises the diagnostic criteria, clinical course and therapeutic management of HCM. Attention is also paid to certain issues of special interest in this disease. ImagesFigure 1Figure 2Figure 4Figure 5Figure 6 PMID:25696443

  18. Mutation analysis of the phospholamban gene in 315 South Africans with dilated, hypertrophic, peripartum and arrhythmogenic right ventricular cardiomyopathies

    PubMed Central

    Fish, Maryam; Shaboodien, Gasnat; Kraus, Sarah; Sliwa, Karen; Seidman, Christine E.; Burke, Michael A.; Crotti, Lia; Schwartz, Peter J.; Mayosi, Bongani M.

    2016-01-01

    Cardiomyopathy is an important cause of heart failure in Sub-Saharan Africa, accounting for up to 30% of adult heart failure hospitalisations. This high prevalence poses a challenge in societies without access to resources and interventions essential for disease management. Over 80 genes have been implicated as a cause of cardiomyopathy. Mutations in the phospholamban (PLN) gene are associated with dilated cardiomyopathy (DCM) and severe heart failure. In Africa, the prevalence of PLN mutations in cardiomyopathy patients is unknown. Our aim was to screen 315 patients with arrhythmogenic right ventricular cardiomyopathy (n = 111), DCM (n = 95), hypertrophic cardiomyopathy (n = 40) and peripartum cardiomyopathy (n = 69) for disease-causing PLN mutations by high resolution melt analysis and DNA sequencing. We detected the previously reported PLN c.25C > T (p.R9C) mutation in a South African family with severe autosomal dominant DCM. Haplotype analysis revealed that this mutation occurred against a different haplotype background to that of the original North American family and was therefore unlikely to have been inherited from a common ancestor. No other mutations in PLN were detected (mutation prevalence = 0.2%). We conclude that PLN is a rare cause of cardiomyopathy in African patients. The PLN p.R9C mutation is not well-tolerated, emphasising the importance of this gene in cardiac function. PMID:26917049

  19. Mutation analysis of the phospholamban gene in 315 South Africans with dilated, hypertrophic, peripartum and arrhythmogenic right ventricular cardiomyopathies.

    PubMed

    Fish, Maryam; Shaboodien, Gasnat; Kraus, Sarah; Sliwa, Karen; Seidman, Christine E; Burke, Michael A; Crotti, Lia; Schwartz, Peter J; Mayosi, Bongani M

    2016-02-26

    Cardiomyopathy is an important cause of heart failure in Sub-Saharan Africa, accounting for up to 30% of adult heart failure hospitalisations. This high prevalence poses a challenge in societies without access to resources and interventions essential for disease management. Over 80 genes have been implicated as a cause of cardiomyopathy. Mutations in the phospholamban (PLN) gene are associated with dilated cardiomyopathy (DCM) and severe heart failure. In Africa, the prevalence of PLN mutations in cardiomyopathy patients is unknown. Our aim was to screen 315 patients with arrhythmogenic right ventricular cardiomyopathy (n = 111), DCM (n = 95), hypertrophic cardiomyopathy (n = 40) and peripartum cardiomyopathy (n = 69) for disease-causing PLN mutations by high resolution melt analysis and DNA sequencing. We detected the previously reported PLN c.25C > T (p.R9C) mutation in a South African family with severe autosomal dominant DCM. Haplotype analysis revealed that this mutation occurred against a different haplotype background to that of the original North American family and was therefore unlikely to have been inherited from a common ancestor. No other mutations in PLN were detected (mutation prevalence = 0.2%). We conclude that PLN is a rare cause of cardiomyopathy in African patients. The PLN p.R9C mutation is not well-tolerated, emphasising the importance of this gene in cardiac function.

  20. Hypertrophic cardiomyopathy

    MedlinePlus

    ... thickness, problems with blood flow, or leaky heart valves ( mitral valve regurgitation ) may include: Echocardiography ECG 24-hour Holter ... You may need surgery to repair the heart's mitral valve if it is leaking. Watch this video about: ...

  1. Shortening baroreflex delay in hypertrophic cardiomyopathy patients – an unknown effect of β-blockers

    PubMed Central

    Katarzynska-Szymanska, Agnieszka; Ochotny, Romuald; Oko-Sarnowska, Zofia; Wachowiak-Baszynska, Hanna; Krauze, Tomasz; Piskorski, Jaroslaw; Gwizdala, Adrian; Mitkowski, Przemyslaw; Guzik, Przemyslaw

    2013-01-01

    Aims Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular hypertrophy and impaired diastolic and systolic function. Abnormal sympathetic–parasympathetic balance is a potential stimulus for left ventricular hypertrophy in HCM patients. β-Blockers are routinely used in HCM for their strong negative inotropic effect; however, these drugs also influence the sympathetic–parasympathetic balance. This study aimed to determine the autonomic control of the cardiovascular system and the autonomic effects of β-blockers in HCM patients treated or untreated with β-blockers. Methods Among 51 HCM outpatients (18–70 years old; 29 men) there were 19 individuals with no medication and 32 subjects treated with a β-blocker. Fourteen age- and gender-matched (23–70 years old; nine men) healthy volunteers were enrolled in the control group. Continuous, non-invasive finger blood pressure was recorded during supine rest for 30 min. Autonomic regulation of the cardiovascular system was measured by heart rate variability and spontaneous baroreflex function (cross-correlation sequence method). Results The mean pulse interval, time domain and spectral measures of heart rate variability and baroreflex sensitivity were comparable between HCM patients, treated or not with β-blockers, and the control group. However, the delay of the baroreflex was significantly longer in HCM patients who were not treated with β-blockers [2.0 (1.6–2.3) s] in comparison with HCM patients receiving β-blockers [1.4 (1.1–1.8) s; P = 0.0072] or control subjects [1.2 (0.8–1.8) s; P = 0.0025]. This delay did not differ between HCM patients treated with β-blockers and the control group. Conclusions Hypertrophic cardiomyopathy not treated with β-blockers is accompanied by prolonged baroreflex delay. The use of β-blockers normalizes this delay. PMID:23126403

  2. Papillary muscle insertion directly into the anterior mitral leaflet in hypertrophic cardiomyopathy, its identification and cause of outflow obstruction by cardiac magnetic resonance imaging, and its surgical management.

    PubMed

    Rowin, Ethan J; Maron, Barry J; Lesser, John R; Rastegar, Hassan; Maron, Martin S

    2013-06-01

    This case presents an uncommon but important mechanism of muscular left ventricular outflow obstruction in hypertrophic cardiomyopathy due to anomalous and direct papillary muscle insertion into the anterior mitral leaflet, a finding reliably identified clinically by cardiac magnetic resonance imaging. The identification of this left ventricular outflow tract morphology is important before invasive ventricular septal reduction therapy because it dictates a specific surgical strategy. These findings further support the role of cardiac magnetic resonance imaging in the early evaluation of hypertrophic cardiomyopathy patients.

  3. [Physiopathology of mitral mechanics in hypertrophic cardiomyopathy. Groupe de travail "Cardiomyopathies et insuffisance cardiaque" de la Société Française de Cardiologie].

    PubMed

    Hagège, A; Desnos, M; Komajda, M; Dubourg, O; Isnard, R; Guicheney, P; Schwartz, K; Lévine, R A

    1994-10-01

    Ventricular hypertrophy, the only indisputable phenotypical marker of hypertrophic cardiomyopathy, is the basis of the physiopathology and treatment of the disease. Mitral valve abnormalities are usually considered to be secondary to the hypertrophy but the genesis of systolic anterior motion by the Venturi effect has been questioned by many clinical and experimental observations. Abnormalities of the mitral valve apparatus may in themselves (elongation of the valves, antero-internal malposition of the mitral papillary muscles and/or hyperlaxicity of antero-internal corhdae tendinae) create systolic anterior motion or subaortic obstruction in the absence of septal hypertrophy and/or increased subaortic flow velocities. Anatomo-clinical studies have confirmed this hypothesis: a high prevalence of mitral valve disease (increased valvular surface and length) has been found in hypertrophic cardiomyopathy. The recognition of these abnormalities is of value from the therapeutic (mitral valvuloplasty) diagnostic (in borderline cases) and genetic (when the primary nature of the abnormalities is confirmed) points of view.

  4. Virtual Cardiac Surgery Using CFD: Application to Septal Myectomy in Obstructive Hypertrophic Cardiomyopathy

    NASA Astrophysics Data System (ADS)

    Vedula, Vijay; Mittal, Rajat; Abraham, Theodore

    2011-11-01

    Obstructive hypertrophic cardiomyopathy (HOCM) is characterized by ventricular wall thickening, diastolic dysfunction, and dynamic outflow tract obstruction, all of which strongly influence the vortex dynamics and pressure distribution in the left ventricle (LV). Severe cases of HCM are usually managed through septal myectomy where the surgeon resects the hypertrophic mass. Surgeons currently try to remove as much tissue as possible in order to optimize the post surgical result. However, excessive debulking increases the chance of ventricular septal defects, bundle branch block or complete heart block, and aneurysmal septal thinning. On the other hand, insufficient tissue removal also leads to unsatisfactory outcomes in terms of reduction of outflow tract pressure gradient. Knowing how much muscle to remove and where to remove it from could reduce the likelihood of complications and suboptimal outcomes. In the present study, we employ an immersed boundary solver to model the effect of septal myectomy for ventricles with HOCM and demonstrate the potential of such an approach for surgical planning. Computational resources were provided by the National Institute of Computational Science under Tergrid grant number TG-CTS100002.

  5. Metabolic crosstalk between the heart and liver impacts familial hypertrophic cardiomyopathy.

    PubMed

    Magida, Jason A; Leinwand, Leslie A

    2014-04-01

    Familial hypertrophic cardiomyopathy (HCM) is largely caused by dominant mutations in genes encoding cardiac sarcomeric proteins, and it is etiologically distinct from secondary cardiomyopathies resulting from pressure/volume overload and neurohormonal or inflammatory stimuli. Here, we demonstrate that decreased left ventricular contractile function in male, but not female, HCM mice is associated with reduced fatty acid translocase (CD36) and AMP-activated protein kinase (AMPK) activity. As a result, the levels of myocardial ATP and triglyceride (TG) content are reduced, while the levels of oleic acid and TG in circulating very low density lipoproteins (VLDLs) and liver are increased. With time, these metabolic changes culminate in enhanced glucose production in male HCM mice. Remarkably, restoration of ventricular TG and ATP deficits via AMPK agonism as well as inhibition of gluconeogenesis improves ventricular architecture and function. These data underscore the importance of the systemic effects of a primary genetic heart disease to other organs and provide insight into potentially novel therapeutic interventions for HCM.

  6. Cardiotrophin-1 plasma levels are associated with the severity of hypertrophy in hypertrophic cardiomyopathy

    PubMed Central

    Monserrat, Lorenzo; López, Begoña; González, Arantxa; Hermida, Manuel; Fernández, Xusto; Ortiz, Martín; Barriales-Villa, Roberto; Castro-Beiras, Alfonso; Díez, Javier

    2011-01-01

    Aims Cardiotrophin-1 (CT-1) is a cytokine that induces hypertrophy in cardiomyocytes and is associated with left ventricular hypertrophy (LVH) in hypertensive patients. The objective of this study was to evaluate whether plasma CT-1 is associated with hypertrophic cardiomyopathy (HCM). Methods and results The study was performed in 124 patients with HCM. All patients underwent a full clinical evaluation and an echocardiogram. Left ventricular hypertrophy was evaluated by the measurement of the maximal LV wall thickness and the Spirito's LVH score. Plasma CT-1 was measured by an enzyme-linked immunosorbent assay. Compared with controls, patients with HCM exhibited higher (P < 0.001) plasma CT-1 levels. Significant correlations were found between CT-1 and maximal LV wall thickness (r = 0.284, P = 0.001) and the Spirito's LVH score (r = 0.287, P = 0.006) in HCM patients. In addition, the levels of CT-1 were higher (P = 0.02) in patients with severe LVH (maximal LV wall thickness ≥30 mm) than in patients with mild or moderate LVH (maximal LV wall thickness <30 mm). Conclusions These findings show that plasma CT-1 is associated with the severity of LVH in patients with HCM. Further studies are required to ascertain whether CT-1 is a diagnostic biomarker of this cardiomyopathy. PMID:21059734

  7. The Role of Cardiac MRI in the Diagnosis and Risk Stratification of Hypertrophic Cardiomyopathy

    PubMed Central

    Maron, Martin S

    2016-01-01

    Hypertrophic cardiomyopathy (HCM), the most common genetic cardiomyopathy, is a disease characterised by substantial heterogeneity. Although the majority of patients with HCM remain asymptomatic with near-normal longevity, a small, but important, subset remain at risk for a wide range of clinical outcomes including sudden death. Cardiovascular magnetic resonance (CMR), with its high spatial resolution and tomographic imaging capability, has emerged as an imaging modality particularly well suited to characterise the phenotypic expression of HCM. CMR helps in the diagnosis of HCM by identifying areas of hypertrophy not well visualised by echocardiography, providing more accurate wall thickness measurements and differentiating HCM from other causes of left ventricular (LV) hypertrophy. CMR has led to the identification of novel subgroups of patients with HCM, including those with LV apical aneurysms (a subgroup at increased risk for ventricular arrhythmias and thromboembolic stroke), as well as abnormalities that contribute to LV outflow obstruction. Additionally, contrast-enhanced CMR with late-gadolinium enhancement (LGE) has recognised patients with extensive LGE (≥15 % LV myocardium) as individuals who may be at increased risk of sudden death, independent of other high-risk features, with implications on management strategies including consideration for primary prevention implantable cardioverter defibrillator therapy. These observations justify an expanded role of CMR in the routine clinical assessment of patients with HCM. PMID:28116085

  8. Effects of hypertrophic and dilated cardiomyopathy mutations on power output by human β-cardiac myosin.

    PubMed

    Spudich, James A; Aksel, Tural; Bartholomew, Sadie R; Nag, Suman; Kawana, Masataka; Yu, Elizabeth Choe; Sarkar, Saswata S; Sung, Jongmin; Sommese, Ruth F; Sutton, Shirley; Cho, Carol; Adhikari, Arjun S; Taylor, Rebecca; Liu, Chao; Trivedi, Darshan; Ruppel, Kathleen M

    2016-01-01

    Hypertrophic cardiomyopathy is the most frequently occurring inherited cardiovascular disease, with a prevalence of more than one in 500 individuals worldwide. Genetically acquired dilated cardiomyopathy is a related disease that is less prevalent. Both are caused by mutations in the genes encoding the fundamental force-generating protein machinery of the cardiac muscle sarcomere, including human β-cardiac myosin, the motor protein that powers ventricular contraction. Despite numerous studies, most performed with non-human or non-cardiac myosin, there is no clear consensus about the mechanism of action of these mutations on the function of human β-cardiac myosin. We are using a recombinantly expressed human β-cardiac myosin motor domain along with conventional and new methodologies to characterize the forces and velocities of the mutant myosins compared with wild type. Our studies are extending beyond myosin interactions with pure actin filaments to include the interaction of myosin with regulated actin filaments containing tropomyosin and troponin, the roles of regulatory light chain phosphorylation on the functions of the system, and the possible roles of myosin binding protein-C and titin, important regulatory components of both cardiac and skeletal muscles.

  9. Ile90Met, a novel mutation in the cardiac troponin T gene for familial hypertrophic cardiomyopathy in a Chinese pedigree.

    PubMed

    Xu, Chao; Wei, Meng; Su, Bin; Hua, Xue-Wei; Zhang, Guo-Wei; Xue, Xiao-Pei; Pan, Cun-Ming; Liu, Rong; Sheng, Yan; Lu, Zhi-Gang; Jin, Li-Ren; Song, Huai-Dong

    2008-10-01

    To identify the disease-causing gene for a large multi-generational Chinese family affected by familial hypertrophic cardiomyopathy (FHCM), genome-wide screening was carried out in a Chinese family with FHCM using micro-satellite markers, and linkage analysis was performed using the MLINK program. The disease locus was mapped to 1q32 in this family. Screening for a mutation in the cardiac troponin T (cTnT) gene was performed by a PCR and sequencing was done with an ABI Prism 3700 sequencer. A novel C-->G transition located in the ninth exon of the cTnT gene, leading to a predicted amino acid residue change from Ile to Met at codon 90, was identified in all individuals with hypertrophic cardiomyopathy (HCM). The results presented here strongly suggest that Ile90Met, a novel mutation in the cTnT gene, is causative agent of HCM in this family.

  10. Obstetric hemorrhage in a case of hypertrophic obstructive cardiomyopathy with automatic implantable cardioverter defibrillator: Anaesthesia and intensive care management.

    PubMed

    Mishra, Sandeep Kumar; Bhat, Ravindra R; Kavitha, Jayaram; Kundra, Pankaj; Parida, Satyen

    2016-01-01

    The physiological changes occurring during pregnancy and labor may reveal or exacerbate the symptoms of hypertrophic obstructive cardiomyopathy (HOCM). The addition of obstetric hemorrhage to this presents a unique challenge to the anesthesiologists and intensivists managing these patients in the operation theatres and the Intensive Care Units. Here we present a case of HOCM with automatic implantable cardioverter defibrillator in situ and postpartum hemorrhagic shock.

  11. Cell-Intrinsic Functional Effects of the α-Cardiac Myosin Arg-403-Gln Mutation in Familial Hypertrophic Cardiomyopathy

    PubMed Central

    Chuan, Peiying; Sivaramakrishnan, Sivaraj; Ashley, Euan A.; Spudich, James A.

    2012-01-01

    Human familial hypertrophic cardiomyopathy is the most common Mendelian cardiovascular disease worldwide. Among the most severe presentations of the disease are those in families heterozygous for the mutation R403Q in β-cardiac myosin. Mice heterozygous for this mutation in the α-cardiac myosin isoform display typical familial hypertrophic cardiomyopathy pathology. Here, we study cardiomyocytes from heterozygous 403/+ mice. The effects of the R403Q mutation on force-generating capabilities and dynamics of cardiomyocytes were investigated using a dual carbon nanofiber technique to measure single-cell parameters. We demonstrate the Frank-Starling effect at the single cardiomyocyte level by showing that cell stretch causes an increase in amplitude of contraction. Mutant 403/+ cardiomyocytes exhibit higher end-diastolic and end-systolic stiffness than +/+ cardiomyocytes, whereas active force generation capabilities remain unchanged. Additionally, 403/+ cardiomyocytes show slowed relaxation dynamics. These phenotypes are consistent with increased end-diastolic and end-systolic chamber elastance, as well as diastolic dysfunction seen at the level of the whole heart. Our results show that these functional effects of the R403Q mutation are cell-intrinsic, a property that may be a general phenomenon in familial hypertrophic cardiomyopathy. PMID:22735528

  12. Assessment of myocardial damage in dilated-phase hypertrophic cardiomyopathy by using indium-111-antimyosin Fab myocardial scintigraphy

    SciTech Connect

    Nishimura, T.; Nagata, S.; Uehara, T.; Hayashida, K.; Mitani, I.; Kumita, S. )

    1991-07-01

    For the detection of myocardial cell damage, an 111In-antimyosin Fab study was carried out on seven patients (Group A) in the dilated phase of hypertrophic cardiomyopathy, seven patients (Group B) with dilated cardiomyopathy, and eight control patients (Group C). Imaging was done 48 hr after intravenous injection of 74 MBq of 111In-antimyosin Fab. Myocardial antimyosin uptake was visually graded as 0, +1, +2 or +3. A score of +2 or +3 was considered positive. The heart/lung ratio of antimyosin uptake (antimyosin index) also was determined. Antimyosin uptake was positive in seven (100%), nine (90%) and no (0%) patients in Groups A, B, and C, respectively. The antimyosin index in Groups A and B was 2.46 {plus minus} 0.49 and 2.04 {plus minus} 0.24, respectively, findings were significantly higher than that in Group C (1.51 {plus minus} 0.13) (p less than 0.01). Positive biopsy findings were noted in only two patients in Group A. Thus, antimyosin uptake was increased in dilated phase hypertrophic cardiomyopathy and dilated cardiomyopathy, which suggests ongoing necrotic changes in these patients.

  13. Cardiac Troponin and Tropomyosin: Structural and Cellular Perspectives to Unveil the Hypertrophic Cardiomyopathy Phenotype

    PubMed Central

    Marques, Mayra de A.; de Oliveira, Guilherme A. P.

    2016-01-01

    Inherited myopathies affect both skeletal and cardiac muscle and are commonly associated with genetic dysfunctions, leading to the production of anomalous proteins. In cardiomyopathies, mutations frequently occur in sarcomeric genes, but the cause-effect scenario between genetic alterations and pathological processes remains elusive. Hypertrophic cardiomyopathy (HCM) was the first cardiac disease associated with a genetic background. Since the discovery of the first mutation in the β-myosin heavy chain, more than 1400 new mutations in 11 sarcomeric genes have been reported, awarding HCM the title of the “disease of the sarcomere.” The most common macroscopic phenotypes are left ventricle and interventricular septal thickening, but because the clinical profile of this disease is quite heterogeneous, these phenotypes are not suitable for an accurate diagnosis. The development of genomic approaches for clinical investigation allows for diagnostic progress and understanding at the molecular level. Meanwhile, the lack of accurate in vivo models to better comprehend the cellular events triggered by this pathology has become a challenge. Notwithstanding, the imbalance of Ca2+ concentrations, altered signaling pathways, induction of apoptotic factors, and heart remodeling leading to abnormal anatomy have already been reported. Of note, a misbalance of signaling biomolecules, such as kinases and tumor suppressors (e.g., Akt and p53), seems to participate in apoptotic and fibrotic events. In HCM, structural and cellular information about defective sarcomeric proteins and their altered interactome is emerging but still represents a bottleneck for developing new concepts in basic research and for future therapeutic interventions. This review focuses on the structural and cellular alterations triggered by HCM-causing mutations in troponin and tropomyosin proteins and how structural biology can aid in the discovery of new platforms for therapeutics. We highlight the

  14. Genetics of hypertrophic cardiomyopathy: advances and pitfalls in molecular diagnosis and therapy.

    PubMed

    Roma-Rodrigues, Catarina; Fernandes, Alexandra R

    2014-01-01

    Hypertrophic cardiomyopathy (HCM) is a primary disease of the cardiac muscle that occurs mainly due to mutations (>1,400 variants) in genes encoding for the cardiac sarcomere. HCM, the most common familial form of cardiomyopathy, affecting one in every 500 people in the general population, is typically inherited in an autosomal dominant pattern, and presents variable expressivity and age-related penetrance. Due to the morphological and pathological heterogeneity of the disease, the appearance and progression of symptoms is not straightforward. Most HCM patients are asymptomatic, but up to 25% develop significant symptoms, including chest pain and sudden cardiac death. Sudden cardiac death is a dramatic event, since it occurs without warning and mainly in younger people, including trained athletes. Molecular diagnosis of HCM is of the outmost importance, since it may allow detection of subjects carrying mutations on HCM-associated genes before development of clinical symptoms of HCM. However, due to the genetic heterogeneity of HCM, molecular diagnosis is difficult. Currently, there are mainly four techniques used for molecular diagnosis of HCM, including Sanger sequencing, high resolution melting, mutation detection using DNA arrays, and next-generation sequencing techniques. Application of these methods has proven successful for identification of mutations on HCM-related genes. This review summarizes the features of these technologies, highlighting their strengths and weaknesses. Furthermore, current therapeutics for HCM patients are correlated with clinically observed phenotypes and are based on the alleviation of symptoms. This is mainly due to insufficient knowledge on the mechanisms involved in the onset of HCM. Tissue engineering alongside regenerative medicine coupled with nanotherapeutics may allow fulfillment of those gaps, together with screening of novel therapeutic drugs and target delivery systems.

  15. Phenotypes and echocardiographic characteristics of a European population of domestic shorthair cats with idiopathic hypertrophic cardiomyopathy.

    PubMed

    Brizard, D; Amberger, C; Hartnack, S; Doherr, M; Lombard, C

    2009-11-01

    111 Domestic Shorthair cats with idiopathic hypertrophic cardiomyopathy were reviewed retrospectively. Two-dimensional echocardiography was used to classify cases in 6 established phenotypes. Hypertrophy was diffuse in 61 % of cats and involved major portions of the ventricular septum and the left ventricular free wall (phenotype D). In the remaining cats, distribution of hypertrophy was more segmental and was identified on the papillary muscles exclusively (phenotype A, 6 %), on the anterior and basal portion of the ventricular septum (phenotype B, 12 %), on the entire septum (phenotype C, 14 %), or on the left ventricular free wall (phenotype E, 7 %). Echocardiographic characteristics and clinical findings were determined for each phenotype to study the correlation between distribution of hypertrophy and clinical implications. 31 cats demonstrated systolic anterior motion of the mitral valve, 75 % of them belonged to phenotype C of hypertrophy. Left ventricular-outflow turbulences were identified more frequently with patterns of hypertrophy involving the ventricular septum (65.5 %), while prevalence of mitral regurgitation was higher when hypertrophy included the papillary muscles (phenotypes A and E, 85 % and 87 %, respectively). Left atrial dilatation occurred more frequently when hypertrophy was diffuse or confined to the left ventricular free wall (61 % of cats with phenotype D or E) rather than to the ventricular septum (31 % of cats with phenotype B or C).

  16. Multiple Sclerosis Presents with Psychotic Symptoms and Coexists with Hypertrophic Cardiomyopathy

    PubMed Central

    Özcan, Muhammed Emin; İnce, Bahri; Karadeli, Hasan Hüseyin; Asil, Talip

    2014-01-01

    Multiple sclerosis (MS) is a demyelinating disease of the central nervous system. Psychiatric symptoms are not infrequent during MS, yet onset of MS with psychosis is rarely encountered. A 27-year-old Caucasian male was admitted due to numbness in his right arm and difficulty in walking. His clinical and laboratorial exams lead to the MS diagnosis. Nine months earlier, he also developed psychotic disorder, not otherwise specified (PD-NOS). His sudden onset of PD-NOS, his rapid and complete response to antipsychotics, and a relatively short interval between psychiatric and neurological signs indicate a high likelihood that PD-NOS was a manifestation of underlying MS. He also suffers from hypertrophic obstructive cardiomyopathy (HOCM). The patient's neurological complaints were recovered with methylprednisolone (1 g/day, i.v.) given for five days. Glatiramer acetate (1 × 1 tb.s.c.) was prescribed for consolidation and, after nine months of his admission, the patient fully recovered from neurological and psychiatric complaints. Interestingly, very recent studies indicate specific alpha-actinin antibodies in MS and alpha-actinin mutations cause HOCM. Thus, concurrence of MS with HOCM can be even a new syndrome, if further genetic studies prove. PMID:25197588

  17. Decreased Exercise Capacity and Sleep-Disordered Breathing in Patients With Hypertrophic Cardiomyopathy

    PubMed Central

    Konecny, Tomas; Geske, Jeffrey B.; Ludka, Ondrej; Orban, Marek; Brady, Peter A.; Abudiab, Muaz M.; Albuquerque, Felipe N.; Placek, Alexander; Kara, Tomas; Sahakyan, Karine R.; Gersh, Bernard J.; Tajik, A. Jamil; Allison, Thomas G.; Ommen, Steve R.

    2015-01-01

    BACKGROUND: Mechanisms of decreased exercise capacity in patients with hypertrophic cardiomyopathy (HCM) are not well understood. Sleep-disordered breathing (SDB) is a highly prevalent but treatable disorder in patients with HCM. The role of comorbid SDB in the attenuated exercise capacity in HCM has not been studied previously. METHODS: Overnight oximetry, cardiopulmonary exercise testing, and echocardiographic studies were performed in consecutive patients with HCM seen at the Mayo Clinic. SDB was considered present if the oxygen desaturation index (number of ≥ 4% desaturations/h) was ≥ 10. Peak oxygen consumption (V.o2peak) (the most reproducible and prognostic measure of cardiovascular fitness) was then correlated with the presence and severity of SDB. RESULTS: A total of 198 patients with HCM were studied (age, 53 ± 16 years; 122 men), of whom 32% met the criteria for the SDB diagnosis. Patients with SDB had decreased V.o2peak compared with those without SDB (16 mL O2/kg/min vs 21 mL O2/kg/min, P < .001). SDB remained significantly associated with V.o2peak after accounting for confounding clinical variables (P < .001) including age, sex, BMI, atrial fibrillation, and coronary artery disease. CONCLUSIONS: In patients with HCM, the presence of SDB is associated with decreased V.o2peak. SDB may represent an important and potentially modifiable contributor to impaired exercise tolerance in this unique population. PMID:25633371

  18. Mutations in COA6 cause cytochrome c oxidase deficiency and neonatal hypertrophic cardiomyopathy.

    PubMed

    Baertling, Fabian; A M van den Brand, Mariel; Hertecant, Jozef L; Al-Shamsi, Aisha; P van den Heuvel, Lambert; Distelmaier, Felix; Mayatepek, Ertan; Smeitink, Jan A; Nijtmans, Leo G J; Rodenburg, Richard J T

    2015-01-01

    COA6/C1ORF31 is involved in cytochrome c oxidase (complex IV) biogenesis. We present a new pathogenic COA6 variant detected in a patient with neonatal hypertrophic cardiomyopathy and isolated complex IV deficiency. For the first time, clinical details about a COA6-deficient patient are given and patient fibroblasts are functionally characterized: COA6 protein is undetectable and steady-state levels of complex IV and several of its subunits are reduced. The monomeric COX1 assembly intermediate accumulates. Using pulse-chase experiments, we demonstrate an increased turnover of mitochondrial encoded complex IV subunits. Although monomeric complex IV is decreased in patient fibroblasts, the CI/CIII2 /CIVn -supercomplexes remain unaffected. Copper supplementation shows a partial rescue of complex IV deficiency in patient fibroblasts. We conclude that COA6 is required for complex IV subunit stability. Furthermore, the proposed role in the copper delivery pathway to complex IV subunits is substantiated and a therapeutic lead for COA6-deficient patients is provided.

  19. Alteration of Time Intervals in Patients With Hypertrophic Cardiomyopathy During an Exercise Echocardiography

    PubMed Central

    Zagatina, Angela; Zhuravskaya, Nadezhda; Tyurina, Tatyana V.

    2011-01-01

    Background Hypertrophic cardiomyopathy (HCM) is often associated with diastolic dysfunction. Theoretically, a more marked alteration of diastolic function is revealed during exercise. Methods and Results We studied 84 persons: 1) 25 patients with HCM, 2) 25 patients with essential arterial hypertension (AH) and 3) 34 healthy controls. Each person performed a treadmill echocardiography. Before and after work, the following parameters were measured: the time interval between the QRS complex and the onset of mitral early diastolic filling velocity (TE), the interval between the QRS complex and the onset of peak early tissue mitral annular velocity (Te’), the isovolumetric relaxation time over the difference of TE and Te’ ratio (IVRT/(TE-Te’)), and changes of the time parameters during the stress test. In comparison with hypertensive and control groups, HCM patients at rest showed a significantly longer TE (448 ± 55 vs. 423 ± 33 vs. 417 ± 24 ms, P < 0.04) and Te’ (446 ± 48 vs. 403 ± 44 vs. 416 ± 38 ms, P < 0.003). After stress the HCM group had a longer Te’ (355 ± 59 vs. 299 ± 40 vs. 292 ± 30 ms, P < 0.000004) and a higher IVRT/(TE-Te’) ratio (3.1 ± 1.5 vs. 0.9 ± 2.4 vs. 1.7 ± 1.2, P < 0.002). Conclusions HCM patients show an alteration in the time parameters not only compared to healthy persons but to hypertensive patients as well.

  20. Investigation of Pathogenic Genes in Chinese sporadic Hypertrophic Cardiomyopathy Patients by Whole Exome Sequencing

    PubMed Central

    Xu, Jing; Li, Zhongshan; Ren, Xianguo; Dong, Ming; Li, Jinxin; Shi, Xingjuan; Zhang, Yu; Xie, Wei; Sun, Zhongsheng; Liu, Xiangdong; Dai, Qiming

    2015-01-01

    Hypertrophic cardiomyopathy (HCM) is a cardiovascular disease with high heterogeneity. Limited knowledge concerning the genetic background of nearly 40% HCM cases indicates there is a clear need for further investigation to explore the genetic pathogenesis of the disease. In this study, we undertook a whole exome sequencing (WES) approach to identify novel candidate genes and mutations associated with HCM. The cohort consisted of 74 unrelated patients with sporadic HCM (sHCM) previously determined to be negative for mutations in eight sarcomere genes. The results showed that 7 of 74 patients (9.5%) had damaging mutations in 43 known HCM disease genes. Furthermore, after analysis combining the Transmission and De novo Association (TADA) program and the ToppGene program, 10 putative genes gained priority. A thorough review of public databases and related literature revealed that there is strong supporting evidence for most of the genes playing roles in various aspects of heart development. Findings from recent studies suggest that the putative and known disease genes converge on three functional pathways: sarcomere function, calcium signaling and metabolism pathway. This study illustrates the benefit of WES, in combination with rare variant analysis tools, in providing valuable insight into the genetic etiology of a heterogeneous sporadic disease. PMID:26573135

  1. Obtaining insurance after DNA diagnostics: a survey among hypertrophic cardiomyopathy mutation carriers.

    PubMed

    Christiaans, Imke; Kok, Tjitske M; van Langen, Irene M; Birnie, Erwin; Bonsel, Gouke J; Wilde, Arthur A M; Smets, Ellen M A

    2010-02-01

    Hypertrophic cardiomyopathy (HCM) is a common hereditary heart disease associated with increased mortality. Disclosure of DNA test results may have social implications such as low access to insurance. In The Netherlands, insurance companies are restricted in the use of genetic information of their clients by the Medical Examination Act. A cross-sectional survey was used to assess the frequency and type of problems encountered by HCM mutation carriers applying for insurance, and associations with carriers' characteristics. The response rate was 86% (228/264). A total of 66 carriers (29%) applied for insurance of whom 39 reported problems (59%) during an average follow-up of 3 years since the DNA test result. More problems were encountered by carriers with manifest disease (P<0.001) and carriers with symptoms of HCM (P=0.049). Carriers identified after predictive DNA testing less frequently experienced problems (P=0.002). Three carriers without manifest HCM reported problems (5% of applicants). Frequently reported problems were higher premium (72%), grant access to medical records (62%), and complete rejection (33%). In conclusion, HCM mutation carriers frequently encounter problems when applying for insurances, often in the case of manifest disease, but the risk assessment of insurance companies is largely justified. Still, 5% of carriers encounter potentially unjustified problems, indicating the necessity to monitor the application of the existing laws and regulations by insurance companies and to educate counselees on the implications of these laws and regulations.

  2. High resolution melting: improvements in the genetic diagnosis of hypertrophic cardiomyopathy in a Portuguese cohort

    PubMed Central

    2012-01-01

    Background Hypertrophic Cardiomyopathy (HCM) is a complex myocardial disorder with a recognized genetic heterogeneity. The elevated number of genes and mutations involved in HCM limits a gene-based diagnosis that should be considered of most importance for basic research and clinical medicine. Methodology In this report, we evaluated High Resolution Melting (HRM) robustness, regarding HCM genetic testing, by means of analyzing 28 HCM-associated genes, including the most frequent 4 HCM-associated sarcomere genes, as well as 24 genes with lower reported HCM-phenotype association. We analyzed 80 Portuguese individuals with clinical phenotype of HCM allowing simultaneously a better characterization of this disease in the Portuguese population. Results HRM technology allowed us to identify 60 mutated alleles in 72 HCM patients: 49 missense mutations, 3 nonsense mutations, one 1-bp deletion, one 5-bp deletion, one in frame 3-bp deletion, one insertion/deletion, 3 splice mutations, one 5'UTR mutation in MYH7, MYBPC3, TNNT2, TNNI3, CSRP3, MYH6 and MYL2 genes. Significantly 22 are novel gene mutations. Conclusions HRM was proven to be a technique with high sensitivity and a low false positive ratio allowing a rapid, innovative and low cost genotyping of HCM. In a short return, HRM as a gene scanning technique could be a cost-effective gene-based diagnosis for an accurate HCM genetic diagnosis and hopefully providing new insights into genotype/phenotype correlations. PMID:22429680

  3. A Delta-Sarcoglycan Gene Polymorphism as a Risk Factor for Hypertrophic Cardiomyopathy

    PubMed Central

    Garrido-Garduño, Martín H.; Pérez-Martínez, Ramón A.; Ruiz, Victor M.; Herrera-Tepatlán, Esteban; Rodríguez-Cruz, Maricela; Jiménez-Vaca, Ana L.; Minauro-Sanmiguel, Fernando; Salamanca-Gómez, Fabio A.

    2012-01-01

    Background: The C allele of c.−94C>G polymorphism of the delta-sarcoglycan gene was associated as a risk factor for coronary spasm in Japanese patients with hypertrophic cardiomyopathy (HCM). Aim: We evaluated whether the c.−94C>G polymorphism can be a risk factor for HCM in Mexican patients. Methods: The polymorphism was genotyped and the risk was estimated in 35 HCM patients and 145 healthy unrelated individuals. Data of this polymorphism reported in Mexican Amerindian populations were included. Results: The C allele frequency in HCM patients was higher with an odds ratio (OR) of 2.37, and the risk for the CC genotype increased to 5.0. The analysis with Mexican Amerindian populations showed that the C allele frequency was significantly higher in HCM patients with an OR of 2.96 and for CC genotype the risk increased to 7.60. Conclusions: The C allele of the c.−94C>G polymorphism is a risk factor for HCM, which is increased by the Amerindian component and can play an important role in the etiology and progression of disease in Mexican patients. PMID:22524166

  4. Coronary flow reserve in hypertrophic cardiomyopathy: relation with microvascular dysfunction and pathophysiological characteristics.

    PubMed

    Kofflard, M J; Michels, M; Krams, R; Kliffen, M; Geleijnse, M L; Ten Cate, F J; Serruys, P W

    2007-01-01

    BACKGROUND.: The decrease in coronary flow reserve (CFR) in hypertrophic cardiomyopathy (HCM) predisposes to myocardial ischaemia, systolic dysfunction and cardiac death. In this study we investigate to which extent haemodynamic, echocardiographic, and histological parameters contribute to the reduction of CFR. METHODS.: In ten HCM patients (mean age 44+/-14 years) and eight heart transplant (HTX) patients (mean age 51+/-6 years) CFR was calculated in the left anterior descending coronary artery. In all subjects haemodynamic, echocardiographic and histological parameters were assessed. The relationship between these variables and CFR was determined using linear regression analysis. RESULTS.: CFR was reduced in HCM compared with HTX patients (1.6+/-0.7 vs. 2.7+/-0.8, p<0.01). An increase in septal thickness (p<0.005), indexed left ventricular (LV) mass (p<0.005), LV end-diastolic pressure (p<0.001), LV outflow tract gradient (p<0.05) and a decrease in arteriolar lumen size (p<0.05) were all related to a reduction in CFR. CONCLUSION.: In HCM patients haemodynamic (LV end-diastolic pressure, LV outflow tract gradient), echocardiographic (indexed LV mass) and histological (% luminal area of the arterioles) changes are responsible for a decrease in CFR. (Neth Heart J 2007;15:209-15.).

  5. Effect of Left Ventricular Outflow Tract Obstruction on Left Atrial Mechanics in Hypertrophic Cardiomyopathy

    PubMed Central

    Williams, Lynne K.; Chan, Raymond H.; Carasso, Shemy; Durand, Miranda; Misurka, Jimmy; Crean, Andrew M.; Ralph-Edwards, Anthony; Gruner, Christiane; Woo, Anna; Lesser, John R.; Maron, Barry J.; Maron, Martin S.; Rakowski, Harry

    2015-01-01

    Left atrial (LA) volumes are known to be increased in hypertrophic cardiomyopathy (HCM) and are a predictor of adverse outcome. In addition, LA function is impaired and is presumed to be due to left ventricular (LV) diastolic dysfunction as a result of hypertrophy and myocardial fibrosis. In the current study, we assess the incremental effect of outflow tract obstruction (and concomitant mitral regurgitation) on LA function as assessed by LA strain. Patients with HCM (50 obstructive, 50 nonobstructive) were compared to 50 normal controls. A subset of obstructive patients who had undergone septal myectomy was also studied. Utilising feature-tracking software applied to cardiovascular magnetic resonance images, LA volumes and functional parameters were calculated. LA volumes were significantly elevated and LA ejection fraction and strain were significantly reduced in patients with HCM compared with controls and were significantly more affected in patients with obstruction. LA volumes and function were significantly improved after septal myectomy. LVOT obstruction and mitral regurgitation appear to further impair LA mechanics. Septal myectomy results in a significant reduction in LA volumes, paralleled by an improvement in function. PMID:26788503

  6. Familial screening and genetic counselling in hypertrophic cardiomyopathy: the Rotterdam experience

    PubMed Central

    Michels, M.; Hoedemaekers, Y.M.; Kofflard, M.J.; Frohn-Mulder, I.; Dooijes, D.; Majoor-Krakauer, D.; Ten Cate, F.J.

    2007-01-01

    Hypertrophic cardiomyopathy (HCM) is a disease characterised by unexplained left ventricular hypertrophy (LVH) (i.e. LVH in the absence of another cardiac or systemic disease that could produce a similar degree of hypertrophy), electrical instability and sudden death (SD). Germline mutations in genes encoding for sarcomere proteins are found in more than half of the cases of unexplained LVH. The autosomal dominant inherited forms of HCM are characterised by incomplete penetrance and variability in clinical and echocardiographic features, prognosis and therapeutic modalities. The identification of the genetic defect in one of the HCM genes allows accurate presymptomatic detection of mutation carriers in a family. Cardiac evaluation of at-risk relatives enables early diagnosis and identification of those patients at high risk for SD, which can be the first manifestation of the disease in asymptomatic persons. In this article we present our experience with genetic testing and cardiac screening in our HCM population and give an overview of the current literature available on this subject. (Neth Heart J 2007;15:184-9.17612681) PMID:17612681

  7. Coronary flow reserve in hypertrophic cardiomyopathy: relation with microvascular dysfunction and pathophysiological characteristics

    PubMed Central

    Kofflard, M.J.; Michels, M.; Krams, R.; Kliffen, M.; Geleijnse, M.L.; Ten Cate, F.J.; Serruys, P.W.

    2007-01-01

    Background. The decrease in coronary flow reserve (CFR) in hypertrophic cardiomyopathy (HCM) predisposes to myocardial ischaemia, systolic dysfunction and cardiac death. In this study we investigate to which extent haemodynamic, echocardiographic, and histological parameters contribute to the reduction of CFR. Methods. In ten HCM patients (mean age 44±14 years) and eight heart transplant (HTX) patients (mean age 51±6 years) CFR was calculated in the left anterior descending coronary artery. In all subjects haemodynamic, echocardiographic and histological parameters were assessed. The relationship between these variables and CFR was determined using linear regression analysis. Results. CFR was reduced in HCM compared with HTX patients (1.6±0.7 vs. 2.7±0.8, p<0.01). An increase in septal thickness (p<0.005), indexed left ventricular (LV) mass (p<0.005), LV end-diastolic pressure (p<0.001), LV outflow tract gradient (p<0.05) and a decrease in arteriolar lumen size (p<0.05) were all related to a reduction in CFR. Conclusion. In HCM patients haemodynamic (LV end-diastolic pressure, LV outflow tract gradient), echocardiographic (indexed LV mass) and histological (% luminal area of the arterioles) changes are responsible for a decrease in CFR. (Neth Heart J 2007;15:209-15.17612685) PMID:17612685

  8. [Hypertrophic cardiomyopathy: a rare cause of vascular dementia. A case report].

    PubMed

    Ben Hamouda, Ibtissem; Tougourti, Mohamed Néjib; Hamza, Mohsen

    2002-07-01

    Herein, we report a case of a 51 year old man who experienced three ischemic cerebral infarcts in a time of few months. The patient consulted after the third accident. Neurological presentation included pseudobulbar syndrome with a mild cognitive deficit, aphasia, left hemiparesia, hemiasomatognosia and homonymous lateral hemianopsia. Cerebral tomodensitometry and magnetic resonance imaging evidenced large infarcts images involving right middle cerebral artery territory and bilateral borderline zones in the junction of the territories of the middle and posterior cerebral arteries. Ambulatory 24 hours ECG recording (Holter) revealed two hits of non-sustained ventricular tachycardia. Transoesophageal echocardiography conveyed to the diagnosis of hypertrophic cardiomyopathy and displayed the presence of a left auricular thrombus. Anticoagulant therapy and rehabilitation allowed a substantial recovering of the patient's cognitive functions and wasting of the intracardiac thrombus. The clinical features observed in our patient meet the recommended DSM IV diagnosis criteria of vascular dementia, an exceptional complication of HCM. The clinical findings, neuroimagery investigation results, and the chronological link between cerebral attacks and cognitive function deterioration argue for a demential syndrome of vascular origin resulting from multiple embolic infarcts involving medium sized arteries (multi-infarct dementia). The authors emphasize the rarity of such observation. HCM must be considered as a potential cause of embolic stroke and likewise a multi-infarct dementia.

  9. Usefulness of Genetic Testing in Hypertrophic Cardiomyopathy: an Analysis Using Real-World Data.

    PubMed

    Alejandra Restrepo-Cordoba, M; Campuzano, Oscar; Ripoll-Vera, Tomás; Cobo-Marcos, Marta; Mademont-Soler, Irene; Gámez, José M; Dominguez, Fernando; Gonzalez-Lopez, Esther; Padron-Barthe, Laura; Lara-Pezzi, Enrique; Alonso-Pulpon, Luis; Brugada, Ramon; Garcia-Pavia, Pablo

    2017-02-01

    This study sought to determine the usefulness of genetic testing to predict evolution in hypertrophic cardiomyopathy (HCM) and to assess the role of genetic testing in clinical practice. Genetic results of 100 HCM patients tested for mutations in ≥10 HCM-causing genes were evaluated. Patients were classified as with poor (group A) or favourable (group B) clinical course. Forty-five pathogenic mutations (PM) were identified in 28 patients (56 %) from group A and in 23 (46 %) from group B (p = 0.317). Only 40 patients (40 %) exhibited PM that had been previously reported and only 15 (15 %) had PM reported in ≥10 individuals. PM associated with poor prognosis were identified in just five patients from group A (10 %). Genetic findings are not useful to predict prognosis in most HCM patients. By contrast, real-world data reinforce the usefulness of genetic testing to provide genetic counselling and to enable cascade genetic screening.

  10. Echocardiography as a Screening Test for Myocardial Scarring in Children with Hypertrophic Cardiomyopathy

    PubMed Central

    Nield, Lynne; Dragulescu, Andreea; Benson, Lee

    2016-01-01

    Introduction. Hypertrophic cardiomyopathy (HCM) is burdened with morbidity and mortality including tachyarrhythmias and sudden cardiac death. These complications are attributed in part to the formation of proarrhythmic scars in the myocardium. The presence of extensive LGE is a risk factor for adverse outcomes in HCM. Late gadolinium enhancement (LGE) cardiac magnetic resonance imaging (cMRI) is the standard for the noninvasive evaluation of myocardial scars. However, echocardiography represents an attractive screening tool for myocardial scarring. The aim of this study was to compare the suitability of echocardiography to detect myocardial scars to the standard of cMRI-LGE. Methods. The cMRI studies and echocardiograms from 56 consecutive children with HCM were independently evaluated for the presence of cMRI-LGE and echocardiographic evidence of scarring by expert readers. Results. Echocardiography had a high sensitivity (93%) and negative predictive value (94%) in comparison to LGE. The false positive rate was high, leading to a low specificity (37%) and a low positive predictive value (35%). Conclusions. Given the poor specificity and positive predictive value, echocardiography is not a suitable screening test for the presence of myocardial scarring in children with HCM. However, children without echocardiographic evidence of myocardial scarring may not need to undergo cardiac magnetic resonance imaging to “rule in” LGE. PMID:27974896

  11. Computational Modeling of Blood Flow and Valve Dynamics in Hearts with Hypertrophic Cardiomyopathy

    NASA Astrophysics Data System (ADS)

    Zheng, Xudong; Mittal, Rajat; Abraham, Theodore; Pinheiro, Aurelio

    2010-11-01

    Hypertrophic Cardiomyopathy (HCM) is a cardiovascular disease manifested by the thickening of the ventricular wall and often leads to a partial obstruction to the blood flow out of the left ventricle. HCM is recognized as one of the most common causes of sudden cardiac death in athletes. In a heart with HCM, the hypertrophy usually narrows the blood flow pathway to the aorta and produces a low pressure zone between the mitral valve and the hypertrophy during systole. This low pressure can suck the mitral valve leaflet back and completely block the blood flow into the aorta. In the current study, a sharp interface immersed boundary method flow solver is employed to study the hemodynamics and valve dynamics inside a heart with HCM. The three-dimensional motion and configuration of the left ventricle including mitral valve leaflets and aortic valves are reconstructed based on echo-cardio data sets. The mechanisms of aortic obstruction associated with HCM are investigated. The long term objective of this study is to develop a computational tool to aid in the assessment and surgical management of HCM.

  12. Hypertrophic cardiomyopathy: present and future, with translation into contemporary cardiovascular medicine.

    PubMed

    Maron, Barry J; Ommen, Steve R; Semsarian, Christopher; Spirito, Paolo; Olivotto, Iacopo; Maron, Martin S

    2014-07-08

    Hypertrophic cardiomyopathy (HCM) is a common inherited heart disease with diverse phenotypic and genetic expression, clinical presentation, and natural history. HCM has been recognized for 55 years, but recently substantial advances in diagnosis and treatment options have evolved, as well as increased recognition of the disease in clinical practice. Nevertheless, most genetically and clinically affected individuals probably remain undiagnosed, largely free from disease-related complications, although HCM may progress along 1 or more of its major disease pathways (i.e., arrhythmic sudden death risk; progressive heart failure [HF] due to dynamic left ventricular [LV] outflow obstruction or due to systolic dysfunction in the absence of obstruction; or atrial fibrillation with risk of stroke). Effective treatments are available for each adverse HCM complication, including implantable cardioverter-defibrillators (ICDs) for sudden death prevention, heart transplantation for end-stage failure, surgical myectomy (or selectively, alcohol septal ablation) to alleviate HF symptoms by abolishing outflow obstruction, and catheter-based procedures to control atrial fibrillation. These and other strategies have now resulted in a low disease-related mortality rate of <1%/year. Therefore, HCM has emerged from an era of misunderstanding, stigma, and pessimism, experiencing vast changes in its clinical profile, and acquiring an effective and diverse management armamentarium. These advances have changed its natural history, with prevention of sudden death and reversal of HF, thereby restoring quality of life with extended (if not normal) longevity for most patients, and transforming HCM into a contemporary treatable cardiovascular disease.

  13. Cardiomyopathy

    MedlinePlus

    ... Valve Prolapse Myocardial Bridge Myocarditis Obstructive Sleep Apnea ... cardiomyopathy (HCM), ischemic cardiomyopathy, restrictive cardiomyopathy Cardiomyopathy means "disease of the heart muscle." ...

  14. Physiological left ventricular hypertrophy or hypertrophic cardiomyopathy in an elite adolescent athlete: role of detraining in resolving the clinical dilemma

    PubMed Central

    Basavarajaiah, S; Wilson, M; Junagde, S; Jackson, G; Whyte, G; Sharma, S

    2006-01-01

    The differentiation of physiological left ventricular hypertrophy (LVH) from hypertrophic cardiomyopathy (HCM) can prove challenging for even the most experienced cardiologists. The case is presented of a 17 year old elite swimmer who had electrocardiographic and echocardiographic features that were highly suggestive of HCM. However, indices of diastolic function were normal and cardiopulmonary exercise testing revealed high peak oxygen consumption in keeping with physiological LVH. To resolve the diagnostic dilemma, the patient underwent detraining for eight weeks, after which, there was complete resolution of the changes seen on electrocardiogram and echocardiogram, indicating physiological LVH rather than HCM. PMID:16864569

  15. Apical aneurysm and myocardial bridging in a patient with hypertrophic cardiomyopathy: association or consequence of the myocardial bridging?

    PubMed

    Foucault, Anthony; Hilpert, Loic; Hédoire, Francois; Saloux, Eric; Gomes, Sophie; Pellissier, Arnaud; Scanu, Patrice; Champ-Rigot, Laure; Milliez, Paul

    2012-01-01

    The identification of high-risk patients with hypertrophic cardiomyopathy (HC) for primary prevention of sudden cardiac death (SCD) remains a challenging issue, since major risk factors sometimes lack specificity. We report the case of a patient with HC and association of apical aneurysm and myocardial bridging who had been initially not implanted because she had only one major risk factor. She subsequently experienced a sustained ventricular tachycardia that finally motivated the implantation. We conclude that it is never an easy decision to implant a preventive implantable cardioverter-defibrillator (ICD). Nevertheless, additional criteria for a better selection of patients who would benefit from an ICD implant are certainly useful.

  16. Inappropriate Shock Due to T-Wave Oversensing by a Subcutaneous ICD after Alcohol Septal Ablation for Hypertrophic Cardiomyopathy.

    PubMed

    Van Dijk, Vincent F; Liebregts, Max; Luermans, Justin G L M; Balt, Jippe C

    2016-03-01

    A 53-year-old female patient with hypertrophic obstructive cardiomyopathy (HOCM) was admitted for alcohol septal ablation (ASA). A subcutaneous internal cardioverter defibrillator (S-ICD) was implanted for primary prevention. After ASA, the patient developed a right bundle branch block, and the S-ICD delivered a total of five inappropriate shocks due to T-wave oversensing (TWOS). TWOS is a relatively frequent cause of inappropriate shocks in S-ICD patients. After invasive treatment for HOCM, there is a risk of developing intraventricular conduction delay and subsequent changes in QRS and T-wave morphology. This should be taken into consideration when ICD indication is evaluated in HOCM patients.

  17. MicroRNA transcriptome profiling in cardiac tissue of hypertrophic cardiomyopathy patients with MYBPC3 mutations.

    PubMed

    Kuster, Diederik W D; Mulders, Joyce; Ten Cate, Folkert J; Michels, Michelle; Dos Remedios, Cristobal G; da Costa Martins, Paula A; van der Velden, Jolanda; Oudejans, Cees B M

    2013-12-01

    Hypertrophic cardiomyopathy (HCM) is predominantly caused by mutations in genes encoding sarcomeric proteins. One of the most frequent affected genes is MYBPC3, which encodes the thick filament protein cardiac myosin binding protein C. Despite the prevalence of HCM, disease pathology and clinical outcome of sarcomeric mutations are largely unknown. We hypothesized that microRNAs (miRNAs) could play a role in the disease process. To determine which miRNAs were changed in expression, miRNA arrays were performed on heart tissue from HCM patients with a MYBPC3 mutation (n=6) and compared with hearts of non-failing donors (n=6). 532 out of 664 analyzed miRNAs were expressed in at least one heart sample. 13 miRNAs were differentially expressed in HCM compared with donors (at p<0.01, fold change ≥ 2). The genomic context of these differentially expressed miRNAs revealed that miR-204 (fold change 2.4 in HCM vs. donor) was located in an intron of the TRPM3 gene, encoding an aspecific cation channel involved in calcium entry. RT-PCR analysis revealed a trend towards TRPM3 upregulation in HCM compared with donor myocardium (fold change 2.3, p=0.078). In silico identification of mRNA targets of differentially expressed miRNAs showed a large proportion of genes involved in cardiac hypertrophy and cardiac beta-adrenergic receptor signaling and we showed reduced phosphorylation of cardiac troponin I in the HCM myocardium when compared with donor. HCM patients with MYBPC3 mutations have a specific miRNA expression profile. Downstream mRNA targets reveal possible involvement in cardiac signaling pathways.

  18. Perturbed Length–Dependent Activation in Human Hypertrophic Cardiomyopathy With Missense Sarcomeric Gene Mutations

    PubMed Central

    Sequeira, Vasco; Wijnker, Paul J.M.; Nijenkamp, Louise L.A.M.; Kuster, Diederik W.D.; Najafi, Aref; Witjas-Paalberends, E. Rosalie; Regan, Jessica A.; Boontje, Nicky; ten Cate, Folkert J.; Germans, Tjeerd; Carrier, Lucie; Sadayappan, Sakthivel; van Slegtenhorst, Marjon A.; Zaremba, Ruud; Foster, D. Brian; Murphy, Anne M.; Poggesi, Corrado; dos Remedios, Cris; Stienen, Ger J.M.; Ho, Carolyn Y.; Michels, Michelle; van der Velden, Jolanda

    2013-01-01

    Rationale High-myofilament Ca2+-sensitivity has been proposed as trigger of disease pathogenesis in familial hypertrophic cardiomyopathy (HCM) based on in vitro and transgenic mice studies. However, myofilament Ca2+-sensitivity depends on protein phosphorylation and muscle length, and at present, data in human are scarce. Objective To investigate whether high-myofilament Ca2+-sensitivity and perturbed length-dependent activation are characteristics for human HCM with mutations in thick- and thin-filament proteins. Methods and Results Cardiac samples from patients with HCM harboring mutations in genes encoding thick (MYH7, MYBPC3) and thin (TNNT2, TNNI3, TPM1) filament proteins were compared with sarcomere mutation-negative HCM and nonfailing donors. Cardiomyocyte force measurements showed higher myofilament Ca2+-sensitivity in all HCM samples and low phosphorylation of protein kinase A (PKA)-targets compared with donors. After exogenous PKA treatment, myofilament Ca2+-sensitivity was either similar (MYBPC3mut, TPM1mut, sarcomere mutation-negative HCM), higher (MYH7mut, TNNT2mut), or even significantly lower (TNNI3mut) compared with donors. Length-dependent activation was significantly smaller in all HCM than in donor samples. PKA treatment increased phosphorylation of PKA-targets in HCM myocardium and normalized length-dependent activation to donor values in sarcomere mutation-negative HCM and HCM with truncating MYBPC3 mutations, but not in HCM with missense mutations. Replacement of mutant by wild-type troponin in TNNT2mut and TNNI3mut corrected length-dependent activation to donor values. Conclusions High-myofilament Ca2+-sensitivity is a common characteristic of human HCM and partly reflects hypophosphorylation of PKA-targets compared with donors. Length-dependent sarcomere activation is perturbed by missense mutations, possibly via post-translational modifications other than PKA-hypophosphorylation or altered protein–protein interactions, and represents a

  19. Myocardial perfusion abnormalities in patients with hypertrophic cardiomyopathy: assessment with thallium-201 emission computed tomography

    SciTech Connect

    O'Gara, P.T.; Bonow, R.O.; Maron, B.J.; Damske, B.A.; Van Lingen, A.; Bacharach, S.L.; Larson, S.M.; Epstein, S.E.

    1987-12-01

    Myocardial ischemia may play a critical role in the symptomatic presentation and natural history of hypertrophic cardiomyopathy (HCM). To assess the relative prevalence and functional significance of myocardial perfusion abnormalities in patients comprising the broad clinical spectrum of HCM, we studied 72 patients (ages 12 to 69 years, mean 40) using thallium-201 emission computed tomography. Imaging was performed immediately after maximal exercise and again after a 3 hr delay. Regional perfusion defects were identified in 41 of the 72 patients (57%). Fixed or only partially reversible defects were evident in 17 patients, 14 of whom (82%) had left ventricular ejection fractions of less than 50% at rest. Twenty-four patients demonstrated perfusion defects during exercise that completely reversed at rest; all had normal or hyperdynamic left ventricular systolic function (ejection fraction greater than or equal to 50%). Perfusion abnormalities were present in all regions of the left ventricle. However, the fixed defects were observed predominantly in segments of the left ventricular wall that were of normal or only mildly increased (15 to 20 mm) thickness; in contrast, a substantial proportion (41%) of the completely reversible defects occurred in areas of moderate-to-marked wall thickness (greater than or equal to 20 mm, p less than .001). Neither a history of chest pain nor its provocation with treadmill exercise was predictive of an abnormal thallium study, since regional perfusion defects were present in 10 of 18 (56%) completely asymptomatic patients, compared with 31 of 54 (58%) symptomatic patients. These data indicate that myocardial perfusion abnormalities occur commonly among patients with HCM. Fixed or only partially reversible defects suggestive of myocardial scar and/or severe ischemia occur primarily in patients with impaired systolic performance.

  20. Verapamil prevents silent myocardial perfusion abnormalities during exercise in asymptomatic patients with hypertrophic cardiomyopathy

    SciTech Connect

    Udelson, J.E.; Bonow, R.O.; O'Gara, P.T.; Maron, B.J.; Van Lingen, A.; Bacharach, S.L.; Epstein, S.E.

    1989-05-01

    Recent studies indicate that reversible 201Tl perfusion defects, compatible with silent myocardial ischemia, commonly develop during exercise in asymptomatic or mildly symptomatic patients with hypertrophic cardiomyopathy (HCM). To determine whether this represents a dynamic process that may be modified favorably by medical therapy, we studied 29 asymptomatic or minimally symptomatic patients with HCM, aged 12-55 years (mean, 28), with exercise 201Tl emission computed tomography under control conditions and again after 1 week of oral verapamil (mean dosage, 453 mg/day). Treadmill time increased slightly during verapamil (21.0 +/- 3.6 to 21.9 +/- 2.7 minutes, p less than 0.005), but peak heart rate-blood pressure product was unchanged (26.3 +/- 6.0 X 10(3)) compared with 25.0 +/- 6.4 X 10(3). Two midventricular short-axis images per study were divided into five regions each, and each of these 10 regions was then analyzed on a 0-2 scale by three observers blinded with regard to the patients' therapy. Average regional scores of 1.5 or less were considered to represent perfusion defects, and a change in regional score of 0.5 or more was considered to constitute a significant change. During control studies, 15 patients (52%) developed perfusion defects with exercise (average, 3.7 regions per patient). In 14 of these patients, all perfusion defects completely reversed after 3 hours of rest; one patient had fixed defects. After administration of verapamil, exercise perfusion scores improved in 10 of the 14 patients (71%) with reversible defects; there was overall improvement in 34 of 50 (68%) regions with initially reversible perfusion defects.

  1. Characteristic systolic waveform of left ventricular longitudinal strain rate in patients with hypertrophic cardiomyopathy.

    PubMed

    Okada, Kazunori; Kaga, Sanae; Mikami, Taisei; Masauzi, Nobuo; Abe, Ayumu; Nakabachi, Masahiro; Yokoyama, Shinobu; Nishino, Hisao; Ichikawa, Ayako; Nishida, Mutsumi; Murai, Daisuke; Hayashi, Taichi; Shimizu, Chikara; Iwano, Hiroyuki; Yamada, Satoshi; Tsutsui, Hiroyuki

    2016-10-18

    We analyzed the waveform of systolic strain and strain-rate curves to find a characteristic left ventricular (LV) myocardial contraction pattern in patients with hypertrophic cardiomyopathy (HCM), and evaluated the utility of these parameters for the differentiation of HCM and LV hypertrophy secondary to hypertension (HT). From global strain and strain-rate curves in the longitudinal and circumferential directions, the time from mitral valve closure to the peak strains (T-LS and T-CS, respectively) and the peak systolic strain rates (T-LSSR and T-CSSR, respectively) were measured in 34 patients with HCM, 30 patients with HT, and 25 control subjects. The systolic strain-rate waveform was classified into 3 patterns ("V", "W", and "√" pattern). In the HCM group, T-LS was prolonged, but T-LSSR was shortened; consequently, T-LSSR/T-LS ratio was distinctly lower than in the HT and control groups. The "√" pattern of longitudinal strain-rate waveform was more frequently seen in the HCM group (74 %) than in the control (4 %) and HT (20 %) groups. Similar but less distinct results were obtained in the circumferential direction. To differentiate HCM from HT, the sensitivity and specificity of the T-LSSR/T-LS ratio <0.34 and the "√"-shaped longitudinal strain-rate waveform were 85 and 63 %, and 74 and 80 %, respectively. In conclusion, in patients with HCM, a reduced T-LSSR/T-LS ratio and a characteristic "√"-shaped waveform of LV systolic strain rate was seen, especially in the longitudinal direction. The timing and waveform analyses of systolic strain rate may be useful to distinguish between HCM and HT.

  2. Intracoronary electrocardiogram during alcohol septal ablation for hypertrophic obstructive cardiomyopathy predicts myocardial injury size.

    PubMed

    Meng, Jing; Qu, Xiaolong; Huang, Haiyun; Zhang, Shanwen; Zhao, Weibo; He, Guoxiang; Song, Zhiyuan; Hu, Houyuan

    2016-01-01

    Alcohol septal ablation (ASA) has been used widely to treat patients with hypertrophic obstructive cardiomyopathy (HOCM). During the routine ASA procedure, it is difficult to detect the septal injury in real-time. The aim of the present study is to assess myocardial injury during ASA by recording intracoronary electrocardiogram (IC-ECG). From 2012 to 2015, 31 HOCM patients were treated with ASA, and IC-ECG was recorded in 21 patients successfully before and after ethanol injection. The elevation of ST-segment on IC-ECG after ethanol injection was expressed as its ratio to the level before injection or the absolute increasing value. Blood samples were collected before and after ASA for measuring changes in cardiac biomarkers. The ratio value of ST-segment elevation was positively correlated with both the amount of ethanol injected (r = 0.645, P = 0.001) and the myocardial injury size (creatine kinase-MB area under the curve (AUC) of CK-MB) (r = 0.466, P = 0.017). The absolute increment of ST-segment was also positively associated with both the amount of ethanol (r = 0.665, P = 0.001) and AUC of CK-MB (0.685, P = 0.001). However, there was no statistical correlation between the reduction of left ventricular outflow tract gradient and ST-segment elevation. Additionally no severe ASA procedure-related complications were observed in our patients. In conclusion, myocardial injury induced by ethanol injection can be assessed immediately by ST-segment elevation on IC-ECG. This study is the first to show that IC-ECG is a useful method for predicting myocardial injury during ASA in real-time.

  3. Body size and metabolic differences in Maine Coon cats with and without hypertrophic cardiomyopathy.

    PubMed

    Freeman, Lisa M; Rush, John E; Meurs, Kathryn M; Bulmer, Barret J; Cunningham, Suzanne M

    2013-02-01

    An interplay between growth, glucose regulation and hypertrophic cardiomyopathy (HCM) may exist, but has not been studied in detail. The purpose of this study was to characterize morphometric features, insulin-like growth factor-1 (IGF-1) and glucose metabolism in Maine Coon cats with HCM. Body weight, body condition score (BCS), head length and width, and abdominal circumference were measured in Maine Coon cats >2 years of age. Echocardiography and thoracic radiography (for measurement of humerus length, and fourth and twelfth vertebrae length) were also performed. Blood was collected for biochemistry profile, DNA testing, insulin and IGF-1. Sixteen of 63 cats had HCM [myosin binding protein C (MYBPC)+, n = 3 and MYBPC-, n = 13] and 47/63 were echocardiographically normal (MYBPC+, n = 17 and MYBPC-, n = 30). There were no significant differences in any measured parameter between MYBPC+ and MYBPC- cats. Cats with HCM were significantly older (P <0.001), heavier (P = 0.006), more obese (P = 0.008), and had longer humeri (P = 0.02) compared with the HCM- group. Cats with HCM also had higher serum glucose (P = 0.01), homeostasis model assessment (HOMA) and IGF-1 (P = 0.01) concentrations, were from smaller litters (P = 0.04), and were larger at 6 months (P = 0.02) and at 1 year of age (P = 0.03). Multivariate analysis revealed that age (P <0.001), BCS (P = 0.03) and HOMA (P = 0.047) remained significantly associated with HCM. These results support the hypothesis that early growth and nutrition, larger body size and obesity may be environmental modifiers of genetic predisposition to HCM. Further studies are warranted to evaluate the effects of early nutrition on the phenotypic expression of HCM.

  4. Myocardial collagen deposition and inflammatory cell infiltration in cats with pre-clinical hypertrophic cardiomyopathy.

    PubMed

    Khor, K H; Campbell, F E; Owen, H; Shiels, I A; Mills, P C

    2015-02-01

    The histological features of feline hypertrophic cardiomyopathy (HCM) have been well documented, but there are no reports describing the histological features in mild pre-clinical disease, since cats are rarely screened for the disease in the early stages before clinical signs are apparent. Histological changes at the early stage of the disease in pre-clinical cats could contribute to an improved understanding of disease aetiology or progression. The aim of this study was to evaluate the histological features of HCM in the left ventricular (LV) myocardium of cats diagnosed with pre-clinical HCM. Clinically healthy cats with normal (n = 11) and pre-clinical HCM (n = 6) were identified on the basis of echocardiography; LV free wall dimensions (LVFWd) and/or interventricular septal wall (IVSd) dimensions during diastole of 6-7 mm were defined as HCM, while equivalent dimensions <5.5 mm were defined as normal. LV myocardial sections were assessed and collagen content and inflammatory cell infiltrates were quantified objectively. Multifocal areas of inflammatory cell infiltration, predominantly lymphocytes, were observed frequently in the left myocardium of cats with pre-clinical HCM. Tissue from cats with pre-clinical HCM also had a higher number of neutrophils and a greater collagen content than the myocardium of normal cats. The myocardium variably demonstrated other features characteristic of HCM, including arteriolar mural hypertrophy and interstitial fibrosis and, to a lesser extent, myocardial fibre disarray and cardiomyocyte hypertrophy. These results suggest that an inflammatory process could contribute to increased collagen content and the myocardial fibrosis known to be associated with HCM.

  5. Physical activity and other health behaviors in adults with hypertrophic cardiomyopathy.

    PubMed

    Reineck, Elizabeth; Rolston, Brice; Bragg-Gresham, Jennifer L; Salberg, Lisa; Baty, Linda; Kumar, Suwen; Wheeler, Matthew T; Ashley, Euan; Saberi, Sara; Day, Sharlene M

    2013-04-01

    The clinical expression of hypertrophic cardiomyopathy (HC) is undoubtedly influenced by modifying genetic and environmental factors. Lifestyle practices such as tobacco and alcohol use, poor nutritional intake, and physical inactivity are strongly associated with adverse cardiovascular outcomes and increased mortality in the general population. Before addressing the direct effect of such modifiable factors on the natural history of HC, it is critical to define their prevalence in this population. A voluntary survey, drawing questions in part from the 2007 to 2008 National Health and Nutrition Examination Survey (NHANES), was posted on the HC Association website and administered to patients with HC at the University of Michigan. Propensity score matching to NHANES participants was used. Dichotomous and continuous health behaviors were analyzed using logistic and linear regression, respectively, and adjusted for body mass index and propensity score quintile. Compared to the matched NHANES participants, the patients with HC reported significantly less alcohol and tobacco use but also less time engaged in physical activity at work and for leisure. Time spent participating in vigorous or moderate activity was a strong predictor of self-reported exercise capacity. The body mass index was greater in the HC cohort than in the NHANES cohort. Exercise restrictions negatively affected emotional well-being in most surveyed subjects. In conclusion, patients with HC are less active than the general United States population. The well-established relation of inactivity, obesity, and cardiovascular mortality might be exaggerated in patients with HC. More data are needed on exercise in those with HC to strike a balance between acute risks and the long-term health benefits of exercise.

  6. Exercise restrictions trigger psychological difficulty in active and athletic adults with hypertrophic cardiomyopathy

    PubMed Central

    Luiten, Rebecca C; Ormond, Kelly; Post, Lisa; Asif, Irfan M; Wheeler, Matthew T; Caleshu, Colleen

    2016-01-01

    Objective We examined the extent and nature of the psychological difficulty experienced by athletic adults with hypertrophic cardiomyopathy (HCM), correlates of that difficulty and coping mechanisms. Methods A survey assessed athletic history and psychological impact of exercise restrictions. LASSO penalised linear regression identified factors associated with psychological difficulty. Semistructured interviews provided deeper insight into the nature and origins of psychological difficulty. Results 54 individuals (33% female, mean age 55.9) completed the survey. The majority were recreational athletes at the time of restriction (67%). There was a drop in athleticism after diagnosis, including time spent exercising (p=0.04) and identification as an athlete (p=0.0005). Most respondents (54%) found it stressful and/or difficult to adjust to exercise restrictions. Greater psychological morbidity was associated with history of elite or competitive athletics, athletic identity and decrease in time spent exercising. 16 individuals (44% female, mean age 52.4) were interviewed. Long-term effects included weight gain and uncertainty about exercising safely. The role of exercise in interviewees' lives contracted significantly after restriction, from multiple functions (eg, social, stress relief, fitness) to solely health maintenance. Interviewees reported a unique form of social support: having family and friends participate with them in lower intensity exercise. Lack of understanding from family or friends and avoiding exercise completely were detrimental to coping. Conclusions Athletic adults with HCM experience multifaceted, lasting difficulty adjusting to exercise recommendations. These data can guide clinicians in identifying patients at highest risk for distress and in helping to bolster coping and adaptation. PMID:27843566

  7. Comparison of Maximal Wall Thickness in Hypertrophic Cardiomyopathy Differs Between Magnetic Resonance Imaging and Transthoracic Echocardiography.

    PubMed

    Bois, John P; Geske, Jeffrey B; Foley, Thomas A; Ommen, Steve R; Pellikka, Patricia A

    2017-02-15

    Left ventricular (LV) wall thickness is a prognostic marker in hypertrophic cardiomyopathy (HC). LV wall thickness ≥30 mm (massive hypertrophy) is independently associated with sudden cardiac death. Presence of massive hypertrophy is used to guide decision making for cardiac defibrillator implantation. We sought to determine whether measurements of maximal LV wall thickness differ between cardiac magnetic resonance imaging (MRI) and transthoracic echocardiography (TTE). Consecutive patients were studied who had HC without previous septal ablation or myectomy and underwent both cardiac MRI and TTE at a single tertiary referral center. Reported maximal LV wall thickness was compared between the imaging techniques. Patients with ≥1 technique reporting massive hypertrophy received subset analysis. In total, 618 patients were evaluated from January 1, 2003, to December 21, 2012 (mean [SD] age, 53 [15] years; 381 men [62%]). In 75 patients (12%), reported maximal LV wall thickness was identical between MRI and TTE. Median difference in reported maximal LV wall thickness between the techniques was 3 mm (maximum difference, 17 mm). Of the 63 patients with ≥1 technique measuring maximal LV wall thickness ≥30 mm, 44 patients (70%) had discrepant classification regarding massive hypertrophy. MRI identified 52 patients (83%) with massive hypertrophy; TTE, 30 patients (48%). Although guidelines recommend MRI or TTE imaging to assess cardiac anatomy in HC, this study shows discrepancy between the techniques for maximal reported LV wall thickness assessment. In conclusion, because this measure clinically affects prognosis and therapeutic decision making, efforts to resolve these discrepancies are critical.

  8. Extended myectomy in the treatment of patients with hypertrophic obstructive cardiomyopathy

    PubMed Central

    Kołsut, Piotr; Różański, Jacek; Dąbrowski, Maciej; Kłopotowski, Mariusz; Kumor, Magda; Kowalski, Mirosław; Kopyłowska, Natalia; Kuriata, Jarosław; Kuśmierczyk, Mariusz

    2016-01-01

    Introduction Partial resection of the septal muscle is a well-established and effective method of surgical treatment for patients with hypertrophic obstructive cardiomyopathy (HOCM). The procedure is characterized by a low operative mortality rate and long-term clinical improvement that has been confirmed in numerous publications. Mitral insufficiency in patients with HOCM is mostly functional due to the effect of systolic anterior motion (SAM). Aim To present the early results of surgical treatment provided to HOCM patients and to compare the effectiveness of two surgical procedures: isolated myectomy and myectomy combined with mitral valve replacement. Material and methods The study analyzed a group of 49 patients (20 women) with HOCM who underwent surgical treatment between 2012 and 2015. Isolated myectomy was performed in 67.25% (n = 33) of patients, myectomy combined with mitral valve replacement in 30.61% (n = 15), and 1 (2.04%) patient underwent myectomy combined with mitral valvuloplasty (papillary muscle repositioning). Results A greater reduction of the left ventricular outflow tract (LVOT) gradient was observed in the population with concomitant mitral valve replacement in comparison to patients after isolated myectomy; the difference was statistically significant (p = 0.020). No significant correlation was observed between residual SAM and the grade of mitral regurgitation (p = 0.699) or between residual SAM and the LVOT gradient (p = 0.280). Conclusions Surgical myectomy is a well-established, effective method of reducing increased LVOT gradients in patients with HOCM. Additional mitral valve replacement may be associated with greater reductions of the LVOT gradient in the early postoperative period. Valve replacement should be considered in patients with concomitant mitral valve degeneration and patients with narrowed left ventricular cavities. PMID:28096824

  9. Biophysical properties of human β-cardiac myosin with converter mutations that cause hypertrophic cardiomyopathy

    PubMed Central

    Kawana, Masataka; Sarkar, Saswata S.; Sutton, Shirley; Ruppel, Kathleen M.; Spudich, James A.

    2017-01-01

    Hypertrophic cardiomyopathy (HCM) affects 1 in 500 individuals and is an important cause of arrhythmias and heart failure. Clinically, HCM is characterized as causing hypercontractility, and therapies are aimed toward controlling the hyperactive physiology. Mutations in the β-cardiac myosin comprise ~40% of genetic mutations associated with HCM, and the converter domain of myosin is a hotspot for HCM-causing mutations; however, the underlying primary effects of these mutations on myosin’s biomechanical function remain elusive. We hypothesize that these mutations affect the biomechanical properties of myosin, such as increasing its intrinsic force and/or its duty ratio and therefore the ensemble force of the sarcomere. Using recombinant human β-cardiac myosin, we characterize the molecular effects of three severe HCM-causing converter domain mutations: R719W, R723G, and G741R. Contrary to our hypothesis, the intrinsic forces of R719W and R723G mutant myosins are decreased compared to wild type and unchanged for G741R. Actin and regulated thin filament gliding velocities are ~15% faster for R719W and R723G myosins, whereas there is no change in velocity for G741R. Adenosine triphosphatase activities and the load-dependent velocity change profiles of all three mutant proteins are very similar to those of wild type. These results indicate that the net biomechanical properties of human β-cardiac myosin carrying these converter domain mutations are very similar to those of wild type or are even slightly hypocontractile, leading us to consider an alternative mechanism for the clinically observed hypercontractility. Future work includes how these mutations affect protein interactions within the sarcomere that increase the availability of myosin heads participating in force production. PMID:28246639

  10. Differentiating hypertrophic cardiomyopathy from athlete's heart: An electrocardiographic and echocardiographic approach.

    PubMed

    Grazioli, Gonzalo; Usín, Domingo; Trucco, Emilce; Sanz, Maria; Montserrat, Silvia; Vidal, Bàrbara; Gutierrez, Josep; Canal, Ramon; Brugada, Josep; Mont, Lluis; Sitges, Marta

    2016-01-01

    Differential diagnosis of hypertrophic cardiomyopathy (HCM) vs athlete's heart is challenging in individuals with mild-moderate left-ventricular hypertrophy. This study aimed to assess ECG and echocardiographic parameters proposed for the differential diagnosis of HCM. The study included 75 men in three groups: control (n=30), "gray zone" athletes with interventricular septum (IVS) measuring 13-15mm (n=25) and HCM patients with IVS of 13-18mm (n=20). The most significant differences were found in relative septal thickness (RST), calculated as the ratio of 2 x IVS to left ventricle end-diastolic diameter (LV-EDD) (0.37, 0.51, 0.71, respectively; p<0.01) and in spatial QRS-T angle as visually estimated (9.8, 33.6, 66.2, respectively; p<0.01). The capacity for differential HCM diagnosis of each of the 5 criteria was assessed using the area under the curve (AUC), as follows: LV-EDD<54 (0.60), family history (0.61), T-wave inversion (TWI) (0.67), spatial QRS-T angle>45 (0.75) and RST>0.54 (0.92). Pearson correlation between spatial QRS-T angle>45 and TWI was 0.76 (p 0.01). The combination of spatial QRS-T angle>45 and RST>0.54 for diagnosis of HCM had an AUC of 0.79. The best diagnostic criteria for HCM was RST>0.54. The spatial QRS-T angle>45 did not add sensitivity if TWI was present. No additional improvement in differential diagnosis was obtained by combining parameters.

  11. Prevalence and clinical correlates of right ventricular dysfunction in patients with hypertrophic cardiomyopathy.

    PubMed

    Finocchiaro, Gherardo; Knowles, Joshua W; Pavlovic, Aleksandra; Perez, Marco; Magavern, Emma; Sinagra, Gianfranco; Haddad, Francois; Ashley, Euan A

    2014-01-15

    Hypertrophic cardiomyopathy (HC) is a disease that mainly affects the left ventricle (LV), however recent studies have suggested that it can also be associated with right ventricular (RV) dysfunction. The objective of this study was to determine the prevalence of RV dysfunction in patients with HC and its relation with LV function and outcome. A total of 324 consecutive patients with HC who received care at Stanford Hospital from 1999 to 2012 were included in the study. A group of 99 prospectively recruited age- and gender-matched healthy volunteers were used as controls. RV function was quantified using the RV fractional area change, tricuspid annular plane systolic excursion (TAPSE), and RV myocardial performance index (RVMPI). Compared with the controls, the patients with HC had a higher RVMPI (0.51 ± 0.18 vs 0.25 ± 0.06, p <0.001) and lower TAPSE (20 ± 3 vs 24 ± 4, p <0.001). RV dysfunction based on an RVMPI >0.4 and TAPSE <16 mm was found in 71% and 11% of the HC and control groups, respectively. Worst LV function and greater pulmonary pressures were independent correlates of RV dysfunction. At an average follow-up of 3.7 ± 2.3 years, 17 patients had died and 4 had undergone heart transplantation. LV ejection fraction <50% and TAPSE <16 mm were independent correlates of outcome (hazard ratio 3.98, 95% confidence interval 1.22 to 13.04, p = 0.02; and hazard ratio 3.66, 95% confidence interval 1.38 to 9.69, p = 0.009, respectively). In conclusion, RV dysfunction based on the RVMPI is common in patients with HC and more frequently observed in patients with LV dysfunction and pulmonary hypertension. RV dysfunction based on the TAPSE was independently associated with an increased likelihood of death or transplantation.

  12. Significance of sarcomere gene mutations analysis in the end-stage phase of hypertrophic cardiomyopathy.

    PubMed

    Biagini, Elena; Olivotto, Iacopo; Iascone, Maria; Parodi, Maria I; Girolami, Francesca; Frisso, Giulia; Autore, Camillo; Limongelli, Giuseppe; Cecconi, Massimiliano; Maron, Barry J; Maron, Martin S; Rosmini, Stefania; Formisano, Francesco; Musumeci, Beatrice; Cecchi, Franco; Iacovoni, Attilio; Haas, Tammy S; Bacchi Reggiani, Maria L; Ferrazzi, Paolo; Salvatore, Francesco; Spirito, Paolo; Rapezzi, Claudio

    2014-09-01

    End-stage hypertrophic cardiomyopathy (ES-HC) has an ominous prognosis. Whether genotype can influence ES-HC occurrence is unresolved. We assessed the spectrum and clinical correlates of HC-associated mutations in a large multicenter cohort with end-stage ES-HC. Sequencing analysis of 8 sarcomere genes (MYH7, MYBPC3, TNNI3, TNNT2, TPM1, MYL2, MYL3, and ACTC1) and 2 metabolic genes (PRKAG2 and LAMP2) was performed in 156 ES-HC patients with left ventricular (LV) ejection fraction (EF) <50%. A comparison among mutated and negative ES-HC patients and a reference cohort of 181 HC patients with preserved LVEF was performed. Overall, 131 mutations (36 novel) were identified in 104 ES-HC patients (67%) predominantly affecting MYH7 and MYBPC3 (80%). Complex genotypes with double or triple mutations were present in 13% compared with 5% of the reference cohort (p = 0.013). The distribution of mutations was otherwise indistinguishable in the 2 groups. Among ES-HC patients, those presenting at first evaluation before the age of 20 had a 30% prevalence of complex genotypes compared with 19% and 21% in the subgroups aged 20 to 59 and ≥60 years (p = 0.003). MYBPC3 mutation carriers with ES-HC were older than patients with MYH7, other single mutations, or multiple mutations (median 41 vs 16, 26, and 28 years, p ≤0.001). Outcome of ES-HC patients was severe irrespective of genotype. In conclusion, the ES phase of HC is associated with a variable genetic substrate, not distinguishable from that of patients with HC and preserved EF, except for a higher frequency of complex genotypes with double or triple mutations of sarcomere genes.

  13. Prognostic significance of radionuclide-assessed diastolic function in hypertrophic cardiomyopathy

    SciTech Connect

    Chikamori, T.; Dickie, S.; Poloniecki, J.D.; Myers, M.J.; Lavender, J.P.; McKenna, W.J. )

    1990-02-15

    To evaluate the prognostic significance of diastolic function in hypertrophic cardiomyopathy (HC), technetium-99m gated equilibrium radionuclide angiography, acquired in list mode, was performed in 161 patients. Five diastolic indexes were calculated. During 3.0 +/- 1.9 years, 13 patients had disease-related deaths. With univariate analysis, these patients were younger (29 +/- 20 vs 42 +/- 16 years; p less than 0.05), had a higher incidence of syncope (p less than 0.025), dyspnea (p less than 0.001), reduced peak filling rate (2.9 +/- 0.9 vs 3.4 +/- 1.0 end-diastolic volume/s; p = 0.09) with increased relative filling volume during the rapid filling period (80 +/- 7 vs 75 +/- 12%; p = 0.06) and decreased atrial contribution (17 +/- 7 vs 22 +/- 11%; p = 0.07). Stepwise discriminant analysis revealed that young age at diagnosis, syncope at diagnosis, reduced peak ejection rate, positive family history, reduced peak filling rate, increased relative filling volume by peak filling rate and concentric left ventricular hypertrophy were the most statistically significant (p = 0.0001) predictors of disease-related death (sensitivity 92%, specificity 76%, accuracy 77%, positive predictive value 25%). Discriminant analysis excluding the diastolic indexes, however, showed similar predictability (sensitivity 92%, specificity 76%, accuracy 78%, positive predictive value 26%). To obtain more homogeneous groups for analysis, patients were classified as survivors or electrically unstable, including sudden death, out-of-hospital ventricular fibrillation and nonsustained ventricular tachycardia during 48-hour ambulatory electrocardiography, and heart failure death or cardiac transplant.

  14. Genetic testing in the management of relatives of patients with hypertrophic cardiomyopathy.

    PubMed

    Tomašov, P; Minárik, M; Zemánek, D; Čadová, P; Homolová, S; Čurilka, K; Pěnička, M; Benešová, L; Belšánová, B; Gregor, P; Veselka, J

    2014-01-01

    Hypertrophic cardiomyopathy is the most common genetic cardiac disease with vast genetic heterogeneity. First-degree relatives of patients with HCM are at 50% risk of inheriting the disease-causing mutation. Genetic testing is helpful in identifying the relatives harbouring the mutations. When genetic testing is not available, relatives need to be examined regularly. We tested a cohort of 99 unrelated patients with HCM for mutations in MYH7, MYBPC3, TNNI3 and TNNT2 genes. In families with identified pathogenic mutation, we performed genetic and clinical examination in relatives to study the influence of genetic testing on the management of the relatives and to study the usefulness of echocardiographic criteria for distinguishing relatives with positive and negative genotype. We identified 38 genetic variants in 47 patients (47 %). Fifteen of these variants in 21 patients (21 %) were pathogenic mutations. We performed genetic testing in 52 relatives (18 of them (35 %) yielding positive results). Genetic testing of one HCM patient allowed us to omit 2.45-5.15 future cardiologic examinations of the relatives. None of the studied echocardiographic criteria were significantly different between the relatives with positive and negative genotypes, with the exception of a combined echocardiographic score (genotype positive vs. genotype negative, 3.316 vs. -0.489, P = 0.01). As a conclusion, our study of HCM patients and their relatives confirmed the role of genetic testing in the management of the relatives and found only limited benefit of the proposed echocardiographic parameters in identifying disease-causing mutation carriers.

  15. Relation Between Temperature Extremes and Symptom Exacerbation in Patients With Hypertrophic Cardiomyopathy.

    PubMed

    Bois, John P; Adams, Jonathon C; Kumar, Gautam; Ommen, Steve R; Nishimura, Rick A; Klarich, Kyle W

    2016-03-15

    Warm temperatures induce peripheral vasodilation, decrease afterload, and may concurrently increase the left ventricular outflow tract (LVOT) gradient. We aimed to assess the impact of subjective ambient temperature on hypertrophic cardiomyopathy (HC) symptoms and determine whether they were associated with LVOT gradient, patient quality of life (QOL), and risk of sudden cardiac death (SCD). We identified consecutive patients with HC presenting to a tertiary referral center. Of the 173 patients in the study, 143 (83%) had HC symptoms, with ambient temperature change worsening symptoms for 72 patients (50%). Symptom exacerbation occurred only with heat for 57 (79%), whereas symptoms were exacerbated with cold only or with cold and heat equally for 15 (21%). Patients affected by any temperature exacerbation more commonly were women (p = 0.009), had a lower QOL (p = 0.04), had a family history of HC (p = 0.007), or underwent myectomy (p = 0.01). A greater proportion of patients with heat-only exacerbation had a family history of HC (p = 0.005) and SCD (p = 0.05). The presence of an LVOT gradient either at rest or with provocation was similar in all groups. In conclusion, although no appreciable difference in LVOT gradients were observed between patient groups, approximately half of the patients with HC reporting symptoms at baseline noted worsening of symptoms with temperature changes, with >75% describing heat-induced symptom exacerbation. Furthermore, affected patients more frequently were women, underwent surgical intervention and device implantation, and had an overall lower QOL.

  16. Physical activity in hypertrophic cardiomyopathy: prevalence of inactivity and perceived barriers

    PubMed Central

    Sweeting, Joanna; Ingles, Jodie; Timperio, Anna; Patterson, Jillian; Ball, Kylie; Semsarian, Christopher

    2016-01-01

    Objectives This study aimed to determine the prevalence of physical inactivity and perceived barriers to physical activity among individuals with hypertrophic cardiomyopathy (HCM), and to determine potential demographic, clinical and health-related factors influencing likelihood of meeting physical activity guidelines. Methods This was a cross-sectional study of consecutive patients (n=198) with HCM attending a specialist HCM centre from July 2014 to November 2015. The primary outcome measure was physical activity (minutes per day), as measured by self-report (International Physical Activity Questionnaire (IPAQ)) and objective means (ActiGraph accelerometer). For both, participants were classified as meeting guidelines if they did at least 150 min per week of physical activity. Quality of life (Short Form-36 V.2, SF-36v2), barriers to exercise and clinical–demographic data were also collected. Results In total, 54.8% of participants did not meet physical activity recommendations based on IPAQ, and 12.7% did not meet guidelines based on accelerometer data. The most commonly identified barriers to exercise were ‘pain interferes with my exercise’ (33%) and ‘I have an injury/disability that stops me’ (29%). Independent factors associated with meeting guidelines included older age (OR 0.66, 95% CI 0.51 to 0.85, p=0.002), higher education level (OR 2.31, 95% CI 1.08 to 4.93, p=0.03), better physical quality of life (OR 1.05, 95% CI 1.0 to 1.09, p=0.05) and more reported barriers (OR 0.71, 95% CI 0.56 to 0.91, p=0.01). Conclusions More than half of the patients with HCM did not meet minimum physical activity recommendations. Several barriers to exercise among individuals with HCM exist, and provide the basis for targeted interventions to promote physical activity and improve overall health in patients with HCM. PMID:27547438

  17. Significance of positive or negative thallium-201 scintigraphy in hypertrophic cardiomyopathy

    SciTech Connect

    von Dohlen, T.W.; Prisant, L.M.; Frank, M.J. )

    1989-09-01

    Myocardial ischemia, fibrosis and infarction may occur in patients with hypertrophic cardiomyopathy (HC) in the absence of epicardial coronary artery disease. To determine their prevalence and relation with common characteristics, stress thallium-201 scintigraphy was performed in 28 patients. Eleven (39%) had positive scans despite normal epicardial coronary arteries (7 patients) or a pretest risk of coronary disease less than or equal to 5% (4 patients). There was no relation between thallium defects and age, sex, chest pain or outflow tract gradients at rest. However, the mean left ventricular ejection fraction was significantly lower in those with perfusion abnormalities compared with those without (64 +/- 15 vs 75 +/- 11%, respectively, p less than 0.05). Also, the mean ventricular septal thickness was greater in patients with positive scans (27 +/- 7 vs 21 +/- 6 mm, p less than 0.05), and there was a nonparametric relation between increasing septal thickness and the frequency of positive scans (p less than 0.025). Seven of 11 patients with positive scans had ventricular tachycardia compared with none among those who had negative scans (p less than 0.001), and 5 of these 11 patients had conduction system disease requiring permanent pacemaker insertion compared with 1 of 17 with negative scans (p less than 0.025). It is concluded that thallium perfusion abnormalities are common in patients with HC in the absence of epicardial coronary disease, and are strongly associated with potentially lethal arrhythmias. Thallium scintigraphy appears to identify a subset of patients with HC at increased risk for sudden death, who therefore require closer follow-up.

  18. Familial hypertrophic cardiomyopathy: functional variance among individual cardiomyocytes as a trigger of FHC-phenotype development

    PubMed Central

    Brenner, Bernhard; Seebohm, Benjamin; Tripathi, Snigdha; Montag, Judith; Kraft, Theresia

    2014-01-01

    Familial hypertrophic cardiomyopathy (FHC) is the most frequent inherited cardiac disease. It has been related to numerous mutations in many sarcomeric and even some non-sarcomeric proteins. So far, however, no common mechanism has been identified by which the many different mutations in different sarcomeric and non-sarcomeric proteins trigger development of the FHC phenotype. Here we show for different MYH7 mutations variance in force pCa-relations from normal to highly abnormal as a feature common to all mutations we studied, while direct functional effects of the different FHC-mutations, e.g., on force generation, ATPase or calcium sensitivity of the contractile system, can be quite different. The functional variation among individual M. soleus fibers of FHC-patients is accompanied by large variation in mutant vs. wildtype β-MyHC-mRNA. Preliminary results show a similar variation in mutant vs. wildtype β-MyHC-mRNA among individual cardiomyocytes. We discuss our previously proposed concept as to how different mutations in the β-MyHC and possibly other sarcomeric and non-sarcomeric proteins may initiate an FHC-phenotype by functional variation among individual cardiomyocytes that results in structural distortions within the myocardium, leading to cellular and myofibrillar disarray. In addition, distortions can activate stretch-sensitive signaling in cardiomyocytes and non-myocyte cells which is known to induce cardiac remodeling with interstitial fibrosis and hypertrophy. Such a mechanism will have major implications for therapeutic strategies to prevent FHC-development, e.g., by reducing functional imbalances among individual cardiomyocytes or by inhibition of their triggering of signaling paths initiating remodeling. Targeting increased or decreased contractile function would require selective targeting of mutant or wildtype protein to reduce functional imbalances. PMID:25346696

  19. Outcomes in hypertrophic cardiomyopathy patients with and without atrial fibrillation: a survival meta-analysis

    PubMed Central

    Masri, Ahmad; Kanj, Mohamed; Thamilarasan, Maran; Wazni, Oussama; Smedira, Nicholas G.; Lever, Harry M.

    2017-01-01

    Background Atrial fibrillation (AF) is a frequent occurrence in patients with hypertrophic cardiomyopathy (HCM). It is associated with worsening symptoms, cardiovascular events, and mortality. We conducted a meta-analysis of studies reporting on mortality in patient with HCM and AF. Methods We searched PubMed, Medline, Embase, Ovid and Cochrane for studies which reported cardiovascular events and mortality in patients with HCM and AF. Outcome was a composite of cardiac mortality and/or all-cause mortality. Mantel Haenszel odds ratio (OR) or hazard ratio (HR) were calculated using random-effects meta-analysis for the prespecified outcome. Heterogeneity was assessed using I2 statistics. Results Six studies met the inclusion criteria. There were 6,858 patients; 1,314 (19%) had history of AF. During a mean follow up that ranged between 4 and 8 years, 405 (30.8%) patients with AF died as compared to 1,011 (18.2%) patients without AF (OR =2.49, 95% CI: 1.85–3.35, P<0.00001, I2=57%). Results persisted with inclusion of studies only reporting specifically on cardiac mortality (OR =2.80, 95% CI: 1.79–4.39, P<0.00001, I2=56%). Also, the mortality difference persisted after exclusion of deaths secondary to stroke in both groups (2 studies, 1,398 patients, OR =2.57, 95% CI: 1.57–4.20, P=0.0002, I2=31%). In three studies (5,857 patients); the presence of AF was associated with a pooled HR of 1.66 (95% CI: 1.29–2.13, P<0.0001, I2=41%). Conclusion Patients with HCM who develop AF have higher risk of mortality and cardiac deaths as compared to HCM patients without AF. PMID:28164011

  20. Biophysical properties of human β-cardiac myosin with converter mutations that cause hypertrophic cardiomyopathy.

    PubMed

    Kawana, Masataka; Sarkar, Saswata S; Sutton, Shirley; Ruppel, Kathleen M; Spudich, James A

    2017-02-01

    Hypertrophic cardiomyopathy (HCM) affects 1 in 500 individuals and is an important cause of arrhythmias and heart failure. Clinically, HCM is characterized as causing hypercontractility, and therapies are aimed toward controlling the hyperactive physiology. Mutations in the β-cardiac myosin comprise ~40% of genetic mutations associated with HCM, and the converter domain of myosin is a hotspot for HCM-causing mutations; however, the underlying primary effects of these mutations on myosin's biomechanical function remain elusive. We hypothesize that these mutations affect the biomechanical properties of myosin, such as increasing its intrinsic force and/or its duty ratio and therefore the ensemble force of the sarcomere. Using recombinant human β-cardiac myosin, we characterize the molecular effects of three severe HCM-causing converter domain mutations: R719W, R723G, and G741R. Contrary to our hypothesis, the intrinsic forces of R719W and R723G mutant myosins are decreased compared to wild type and unchanged for G741R. Actin and regulated thin filament gliding velocities are ~15% faster for R719W and R723G myosins, whereas there is no change in velocity for G741R. Adenosine triphosphatase activities and the load-dependent velocity change profiles of all three mutant proteins are very similar to those of wild type. These results indicate that the net biomechanical properties of human β-cardiac myosin carrying these converter domain mutations are very similar to those of wild type or are even slightly hypocontractile, leading us to consider an alternative mechanism for the clinically observed hypercontractility. Future work includes how these mutations affect protein interactions within the sarcomere that increase the availability of myosin heads participating in force production.

  1. Pathogenesis of hypertrophic cardiomyopathy caused by myozenin 2 mutations is independent of calcineurin activity

    PubMed Central

    Ruggiero, Alessandra; Chen, Suet Nee; Lombardi, Raffaella; Rodriguez, Gabriela; Marian, Ali J.

    2013-01-01

    Aims The role of calcineurin protein phosphatase 2B (PP2B) in the pathogenesis of human hypertrophic cardiomyopathy (HCM) remains unsettled. We determined potential involvement of calcineurin in the pathogenesis of HCM caused by mutations in myozenin 2 (MYOZ2), an inhibitor of calcineurin. Methods and results We generated multiple lines of transgenic mice expressing either Flag-tagged wild-type (WT) (MYOZ2WT) or mutant MYOZ2S48P and MYOZ2I246M, identified in families with HCM, in the heart. To mimic the human genotype, we generated bigenic mice expressing WT and mutant MYOZ2 in the background of hemizygous endogenous MYOZ2 (Myoz2+/−). Transgene proteins constituted 15–48% of the total MYOZ2 protein in the heart. Mutant MYOZ2 mice showed molecular, cellular, and gross cardiac hypertrophy, preserved systolic function, and interstitial fibrosis. Immunofluorescence staining showed co-localization of WT and mutant MYOZ2 proteins with α-actinin at the Z disks. Electron microscopy showed disrupted and mal-aligned Z disks in the mutant mice. Cardiac calcineurin activity, determined by quantifying Rcan1.4 mRNA and protein levels, luciferase activity in triple transgenic Myoz2+/−:NFATc-Luc:MYOZ2I246M and Myoz2+/−:NFATc-Luc:MYOZ2WT mice, and NFATc transcriptional activity assay, was unchanged in the mutant transgenic mice. However, levels of phospho-ERK1/2 and JNK54/46 were altered in the transgenic mice. Likewise, lentiviral-mediated expression of the MYOZ2I246M did not affect RCAN1.4 and calcineurin (PPP3CB) protein levels. Conclusions Thus, the cardiac phenotype in HCM caused by MYOZ2 mutations might be independent of calcineurin activity in the heart. Z disk abnormalities might provide the stimulus for the induction of cardiac hypertrophy caused by MYOZ2 mutations. PMID:22987565

  2. Diltiazem Treatment for Preclinical Hypertrophic Cardiomyopathy Mutation Carriers: A Pilot Randomized Trial to Modify Disease Expression

    PubMed Central

    Ho, Carolyn Y.; Lakdawala, Neal K.; Cirino, Allison L.; Lipshultz, Steven E.; Sparks, Elizabeth; Abbasi, Siddique A.; Kwong, Raymond Y.; Antman, Elliott M.; Semsarian, Christopher; González, Arantxa; López, Begoña; Diez, Javier; Orav, E. John; Colan, Steven D.; Seidman, Christine E.

    2014-01-01

    Background Hypertrophic cardiomyopathy (HCM) is caused by sarcomere mutations and characterized by left ventricular hypertrophy (LVH) with increased risk of heart failure and sudden death. HCM typically cannot be diagnosed early in life, although subtle phenotypes are present. Animal studies indicate alterations in intracellular calcium handling before LVH develops. Furthermore, early treatment with diltiazem appeared to attenuate disease emergence. Objectives To assess the safety, feasibility, and effect of diltiazem as disease-modifying therapy for at-risk HCM mutation carriers. Methods In a pilot, double-blind trial, we randomly assigned 38 sarcomere mutation carriers without LVH (mean age 15.8 years) to therapy with diltiazem 360 mg/day (or 5 mg/kg/day) or placebo. Treatment duration ranged from 12 to 42 months (median 25 months). Study procedures included electrocardiography, echocardiography, cardiac magnetic resonance imaging, and serum biomarker measurement. Results Diltiazem was not associated with serious adverse events. Heart rate and blood pressure did not differ significantly between groups. However, mean left ventricular end diastolic diameter improved towards normal in the diltiazem group but decreased further in controls (change in z-scores, +0.6 vs. −0.5; P<0.001). Mean LV thickness-to-dimension ratio was stable in the diltiazem group, but increased in controls (−0.02 vs. +0.15; P=0.04). Among MYBPC3 mutation carriers, LV wall thickness and mass, diastolic filling, and cardiac troponin I levels improved in those taking diltiazem compared with controls. Four participants developed overt HCM, two in each treatment group. Conclusions Preclinical administration of diltiazem is safe and may improve early LV remodeling in HCM. This novel strategy merits further exploration. PMID:25543971

  3. Morphological and Electrical Characteristics in Patient with Hypertrophic Cardiomyopathy: Quantitative Analysis of 864 Korean Cohort

    PubMed Central

    Kim, Sung-Hwan; Nam, Gi-Byoung; Choi, Kee-Joon; Kim, Dae Hee; Song, Jong-Min; Kang, Duk-Hyun; Song, Jae-Kwan; Kim, You-Ho

    2015-01-01

    Purpose Although several studies have reported the morphological and electrical characteristics in patients with hypertrophic cardiomyopathy (HCM), comparison between asymmetric and apical HCM has not been investigated in a reasonably sized cohort. Materials and Methods Echocardiography and electrocardiography were quantitatively analyzed in patients with HCM in a Korean tertiary referral center. Results Of 864 patients (mean age 55.4±14.2 years, 68.9% men), 255 (29.5%) patients had apical HCM, 553 (64.0%) patients asymmetric HCM, and 56 (6.4%) patients mixed type HCM. In echocardiographic evaluations, about three quarters of patients (75.8%) had left atrial enlargement. Left ventricular (LV) dilatations and systolic dysfunction were observed in 6.1% and 2.4%, respectively. QRS widening, PR prolongation, and pathologic Q wave are frequent in patients with asymmetric HCM, while LV strain is frequent in patient with apical HCM. The prevalence of J-point elevations (9.4% in inferior, 2.2% in lateral leads) were substantially higher than that in general population. Giant negative T wave was observed in 15.0% of total patients (32.2% in apical, 6.2% in asymmetric, 25% in mixed type). There was no significant correlation between the thickness of the apical wall and the amplitude of T wave inversion (r=-0.005, p=0.71). Conclusion In a large cohort of HCM including apical type, repolarization abnormalities, including early repolarization and QT prolongation as well as LV strain, were significantly observed. T wave inversion was not appropriate for screening of HCM and not correlated with apical wall thickness. PMID:26446631

  4. Recent Advances in the Molecular Genetics of Familial Hypertrophic Cardiomyopathy in South Asian Descendants

    PubMed Central

    Kraker, Jessica; Viswanathan, Shiv Kumar; Knöll, Ralph; Sadayappan, Sakthivel

    2016-01-01

    The South Asian population, numbered at 1.8 billion, is estimated to comprise around 20% of the global population and 1% of the American population, and has one of the highest rates of cardiovascular disease. While South Asians show increased classical risk factors for developing heart failure, the role of population-specific genetic risk factors has not yet been examined for this group. Hypertrophic cardiomyopathy (HCM) is one of the major cardiac genetic disorders among South Asians, leading to contractile dysfunction, heart failure, and sudden cardiac death. This disease displays autosomal dominant inheritance, and it is associated with a large number of variants in both sarcomeric and non-sarcomeric proteins. The South Asians, a population with large ethnic diversity, potentially carries region-specific polymorphisms. There is high variability in disease penetrance and phenotypic expression of variants associated with HCM. Thus, extensive studies are required to decipher pathogenicity and the physiological mechanisms of these variants, as well as the contribution of modifier genes and environmental factors to disease phenotypes. Conducting genotype-phenotype correlation studies will lead to improved understanding of HCM and, consequently, improved treatment options for this high-risk population. The objective of this review is to report the history of cardiovascular disease and HCM in South Asians, present previously published pathogenic variants, and introduce current efforts to study HCM using induced pluripotent stem cell-derived cardiomyocytes, next-generation sequencing, and gene editing technologies. The authors ultimately hope that this review will stimulate further research, drive novel discoveries, and contribute to the development of personalized medicine with the aim of expanding therapeutic strategies for HCM. PMID:27840609

  5. Evaluation of the flanking nucleotide sequences of sarcomeric hypertrophic cardiomyopathy substitution mutations.

    PubMed

    Meurs, Kathryn M; Mealey, Katrina L

    2008-07-03

    Hypertrophic cardiomyopathy (HCM) is a familial myocardial disease with a prevalence of 1 in 500. More than 400 causative mutations have been identified in 13 sarcomeric and myofilament related genes, 350 of these are substitution mutations within eight sarcomeric genes. Within a population, examples of recurring identical disease causing mutations that appear to have arisen independently have been noted as well as those that appear to have been inherited from a common ancestor. The large number of novel HCM mutations could suggest a mechanism of increased mutability within the sarcomeric genes. The objective of this study was to evaluate the most commonly reported HCM genes, beta myosin heavy chain (MYH7), myosin binding protein C, troponin I, troponin T, cardiac regulatory myosin light chain, cardiac essential myosin light chain, alpha tropomyosin and cardiac alpha-actin for sequence patterns surrounding the substitution mutations that may suggest a mechanism of increased mutability. The mutations as well as the 10 flanking nucleotides were evaluated for frequency of di-, tri- and tetranucleotides containing the mutation as well as for the presence of certain tri- and tetranculeotide motifs. The most common substitutions were guanine (G) to adenine (A) and cytosine (C) to thymidine (T). The CG dinucleotide had a significantly higher relative mutability than any other dinucleotide (p<0.05). The relative mutability of each possible trinucleotide and tetranucleotide sequence containing the mutation was calculated; none were at a statistically higher frequency than the others. The large number of G to A and C to T mutations as well as the relative mutability of CG may suggest that deamination of methylated CpG is an important mechanism for mutation development in at least some of these cardiac genes.

  6. Evaluation of apical subtype of hypertrophic cardiomyopathy using cardiac magnetic resonance imaging with gadolinium enhancement.

    PubMed

    Kebed, Kalie Y; Al Adham, Raed I; Bishu, Kalkidan; Askew, J Wells; Klarich, Kyle W; Araoz, Philip A; Foley, Thomas A; Glockner, James F; Nishimura, Rick A; Anavekar, Nandan S

    2014-09-01

    Apical hypertrophic cardiomyopathy (HC) is an uncommon variant of HC. We sought to characterize cardiac magnetic resonance imaging (MRI) findings among apical HC patients. This was a retrospective review of consecutive patients with a diagnosis of apical HC who underwent cardiac MRI examinations at the Mayo Clinic (Rochester, MN) from August 1999 to October 2011. Clinical and demographic data at the time of cardiac MRI study were abstracted. Cardiac MRI study and 2-dimensional echocardiograms performed within 6 months of the cardiac MRI were reviewed; 96 patients with apical HC underwent cardiac MRI examinations. LV end-diastolic and end-systolic volumes were 130.7 ± 39.1 ml and 44.2 ± 20.9 ml, respectively. Maximum LV thickness was 19 ± 5 mm. Hypertrophy extended beyond the apex into other segments in 57 (59.4%) patients. Obstructive physiology was seen in 12 (12.5%) and was more common in the mixed apical phenotype than the pure apical (19.3 vs 2.6%, p = 0.02). Apical pouches were noted in 39 (40.6%) patients. Late gadolinium enhancement (LGE) was present in 70 (74.5%) patients. LGE was associated with severe symptoms and increased maximal LV wall thickness. In conclusion, cardiac MRI is well suited for studying the apical form of HC because of difficulty imaging the cardiac apex with standard echocardiography. Cardiac MRI is uniquely suited to delineate the presence or absence of an apical pouch and abnormal myocardial LGE that may have implications in the natural history of apical HM. In particular, the presence of abnormal LGE is associated with clinical symptoms and increased wall thickness.

  7. Magnesium status and the effect of magnesium supplementation in feline hypertrophic cardiomyopathy.

    PubMed Central

    Freeman, L M; Brown, D J; Smith, F W; Rush, J E

    1997-01-01

    Magnesium deficiency has been associated with the development of cardiovascular disease in several species. Cats may be predisposed to alterations in magnesium status because of recent changes in the composition of commercial feline diets. The purposes of this study were 1) to examine the dietary history of cats with hypertrophic cardiomyopathy (HCM), 2) to study magnesium status of cats with HCM compared to normal cats, and 3) to determine the effects of magnesium supplementation in cats with HCM. In part 1 of the study, diets of 65 cats with HCM were examined retrospectively. Forty of the 45 cats for which diets could be determined (89%) ate a diet designed to be magnesium-restricted and/or to produce an acidic urine. In part 2 of the study, 10 cats with HCM were compared to 10 healthy control cats for serum creatinine and magnesium; urine creatinine and magnesium, urine specific gravity and pH, and fractional excretion of magnesium. Urine creatinine and specific gravity were higher in control cats than in cats with HCM. No other differences were found between the 2 groups. In part 3, cats with HCM were supplemented with either 210 mg magnesium chloride (n = 15) or 210 mg lactose (n = 15) for 12 wk. No differences between the 2 groups were found for changes in either magnesium status or echocardiographic parameters. However, the 30 cats with HCM, as a group, did show significant improvements in measures of cardiac hypertrophy over the 12-week period. This was likely the result of treatment with other medications, rather than the magnesium supplementation. The results of this study suggest that cats with HCM are likely to be fed magnesium-restricted diets, but that they do not appear to have altered magnesium status compared to healthy controls. PMID:9243004

  8. [Exercise echocardiography in different types of hypertension classified by left ventricular geometry; comparison with hypertrophic cardiomyopathy].

    PubMed

    Asai, M; Oki, T; Kawahara, K; Takemura, H; Fukuda, N; Sakai, H; Tominaga, T; Murao, A; Ohshima, C; Niki, T

    1983-06-01

    We investigated left ventricular (LV) function in 40 patients (pts) with hypertension (HT), 16 pts with hypertrophic cardiomyopathy (HCM), 3 pts with ASH and HT and in 27 control subjects by M-mode echocardiography using supine exercise (50 watts, 3 minutes). The hypertensive subjects were echocardiographically divided into three subsets; the normal LV (17 cases), the hypertrophied LV (17 cases) and the dilated LV (6 cases). Similarly, pts with HCM were echocardiographically and cineangiographically divided into three subsets; ASH (asymmetric septal hypertrophy, 6 cases), APH (predominant apical hypertrophy, 6 cases) and DFH (diffuse left ventricular hypertrophy, 4 cases). Changes of left ventricular dimension Controls and HT: Stroke volume was increased during exercise in the controls, normal LV and hypertrophied LV groups by decreasing LV end-systolic dimension ( LVDs ), but it was increased in dilated LV group by increasing LV end-diastolic dimension ( LVDd ) (Frank-Starling mechanism). LVDd was increased transiently in the controls and normal LV group during recovery, but its grade and duration were more pronounced in the latter. LVDd did not change significantly in hypertrophied and the dilated LV groups. HCM: LVDd and LVDs did not change significantly during exercise in all 3 groups. LVDd was increased transiently during recovery in ASH group, but not in the other groups. Changes of peak velocity of circumferential fiber shortening (VCF) and the ratio of peak systolic blood pressure to LV end-systolic volume (PSP/ LVVs ). Controls and HT: Peak VCF was increased during exercise most markedly in the normal LV group, but it was not increased in the dilated LV group. PSP/ LVVs was increased significantly during exercise in the controls, the normal and hypertrophied LV groups, but not in the dilated LV group. HCM: Peak VCF showed a significant increase during exercise in ASH group, but not in the other two groups. Changes of the D/S ratio. The ratio of systolic to

  9. Downregulation of GSTK1 Is a Common Mechanism Underlying Hypertrophic Cardiomyopathy

    PubMed Central

    Sasagawa, Shota; Nishimura, Yuhei; Okabe, Shiko; Murakami, Soichiro; Ashikawa, Yoshifumi; Yuge, Mizuki; Kawaguchi, Koki; Kawase, Reiko; Okamoto, Ryuji; Ito, Masaaki; Tanaka, Toshio

    2016-01-01

    Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular hypertrophy and is associated with a number of potential outcomes, including impaired diastolic function, heart failure, and sudden cardiac death. Various etiologies have been described for HCM, including pressure overload and mutations in sarcomeric and non-sarcomeric genes. However, the molecular pathogenesis of HCM remains incompletely understood. In this study, we performed comparative transcriptome analysis to identify dysregulated genes common to five mouse HCM models of differing etiology: (i) mutation of myosin heavy chain 6, (ii) mutation of tropomyosin 1, (iii) expressing human phospholamban on a null background, (iv) knockout of frataxin, and (v) transverse aortic constriction. Gene-by-gene comparison identified five genes dysregulated in all five HCM models. Glutathione S-transferase kappa 1 (Gstk1) was significantly downregulated in the five models, whereas myosin heavy chain 7 (Myh7), connective tissue growth factor (Ctgf), periostin (Postn), and reticulon 4 (Rtn4) were significantly upregulated. Gene ontology comparison revealed that 51 cellular processes were significantly enriched in genes dysregulated in each transcriptome dataset. Among them, six processes (oxidative stress, aging, contraction, developmental process, cell differentiation, and cell proliferation) were related to four of the five genes dysregulated in all HCM models. GSTK1 was related to oxidative stress only, whereas the other four genes were related to all six cell processes except MYH7 for oxidative stress. Gene–gene functional interaction network analysis suggested correlative expression of GSTK1, MYH7, and actin alpha 2 (ACTA2). To investigate the implications of Gstk1 downregulation for cardiac function, we knocked out gstk1 in zebrafish using the clustered regularly interspaced short palindromic repeats/Cas9 system. We found that expression of the zebrafish homologs of MYH7, ACTA2, and actin alpha 1

  10. Clinical features, spectrum of causal genetic mutations and outcome of hypertrophic cardiomyopathy in South Africans

    PubMed Central

    Ntusi, Ntobeko AB; Shaboodien, Gasnat; Badri, Motasim; Mayosi, Bongani M; Badri, Motasim; Gumedze, Freedom

    2016-01-01

    Summary Background Little is known about the clinical characteristics, spectrum of causal genetic mutations and outcome of hypertrophic cardiomyopathy (HCM) in Africans. The objective of this study was to delineate the clinical and genetic features and outcome of HCM in African patients. Methods Information on clinical presentation, electrocardiographic and echocardiographic findings, and outcome of cases with HCM was collected from the Cardiac Clinic at Groote Schuur Hospital over a mean duration of follow up of 9.1 ± 3.4 years. Genomic DNA was screened for mutations in 15 genes that cause HCM, i.e. cardiac myosinbinding protein C (MYBPC3), cardiac β-myosin heavy chain (MYH7), cardiac troponin T2 (TNNT2), cardiac troponin I (TNNI3), regulatory light chain of myosin (MYL2), essential light chain of myosin (MYL3), tropomyosin 1 (TPM1), phospholamban (PLN), α-actin (ACTC1), cysteine and glycine-rich protein 3 (CSRP3), AMP-activated protein kinase (PRKAG2), α-galactosidase (GLA), four-and-a-half LIM domains 1 (FHL1), lamin A/C (LMNA) and lysosomeassociated membrane protein 2 (LAMP2). Survival and its predictors were analysed using the Kaplan–Meier and Cox proportional hazards regression methods, respectively. Results Forty-three consecutive patients [mean age 38.5 ± 14.3 years; 25 (58.1%) male; and 13 (30.2%) black African] were prospectively enrolled in the study from January 1996 to December 2012. Clinical presentation was similar to that reported in other studies. The South African founder mutations that cause HCM were not found in the 42 probands. Ten of 35 index cases (28.6%) tested for mutations in 15 genes had disease-causing mutations in MYH7 (six cases or 60%) and MYBPC3 (four cases or 40%). No disease-causing mutation was found in the other 13 genes screened. The annual mortality rate was 2.9% per annum and overall survival was 74% at 10 years, which was similar to the general South African population. Cox’s proportional hazards regression showed

  11. Targeted next-generation sequencing helps to decipher the genetic and phenotypic heterogeneity of hypertrophic cardiomyopathy

    PubMed Central

    Cecconi, Massimiliano; Parodi, Maria I.; Formisano, Francesco; Spirito, Paolo; Autore, Camillo; Musumeci, Maria B.; Favale, Stefano; Forleo, Cinzia; Rapezzi, Claudio; Biagini, Elena; Davì, Sabrina; Canepa, Elisabetta; Pennese, Loredana; Castagnetta, Mauro; Degiorgio, Dario; Coviello, Domenico A.

    2016-01-01

    Hypertrophic cardiomyopathy (HCM) is mainly associated with myosin, heavy chain 7 (MYH7) and myosin binding protein C, cardiac (MYBPC3) mutations. In order to better explain the clinical and genetic heterogeneity in HCM patients, in this study, we implemented a target-next generation sequencing (NGS) assay. An Ion AmpliSeq™ Custom Panel for the enrichment of 19 genes, of which 9 of these did not encode thick/intermediate and thin myofilament (TTm) proteins and, among them, 3 responsible of HCM phenocopy, was created. Ninety-two DNA samples were analyzed by the Ion Personal Genome Machine: 73 DNA samples (training set), previously genotyped in some of the genes by Sanger sequencing, were used to optimize the NGS strategy, whereas 19 DNA samples (discovery set) allowed the evaluation of NGS performance. In the training set, we identified 72 out of 73 expected mutations and 15 additional mutations: the molecular diagnosis was achieved in one patient with a previously wild-type status and the pre-excitation syndrome was explained in another. In the discovery set, we identified 20 mutations, 5 of which were in genes encoding non-TTm proteins, increasing the diagnostic yield by approximately 20%: a single mutation in genes encoding non-TTm proteins was identified in 2 out of 3 borderline HCM patients, whereas co-occuring mutations in genes encoding TTm and galactosidase alpha (GLA) altered proteins were characterized in a male with HCM and multiorgan dysfunction. Our combined targeted NGS-Sanger sequencing-based strategy allowed the molecular diagnosis of HCM with greater efficiency than using the conventional (Sanger) sequencing alone. Mutant alleles encoding non-TTm proteins may aid in the complete understanding of the genetic and phenotypic heterogeneity of HCM: co-occuring mutations of genes encoding TTm and non-TTm proteins could explain the wide variability of the HCM phenotype, whereas mutations in genes encoding only the non-TTm proteins are identifiable in

  12. Constitutive phosphorylation of cardiac myosin regulatory light chain prevents development of hypertrophic cardiomyopathy in mice

    SciTech Connect

    Yuan, Chen-Ching; Muthu, Priya; Kazmierczak, Katarzyna; Liang, Jingsheng; Huang, Wenrui; Irving, Thomas C.; Kanashiro-Takeuchi, Rosemeire M.; Hare, Joshua M.; Szczesna-Cordary, Danuta

    2015-06-29

    Myosin light chain kinase (MLCK)-dependent phosphorylation of the regulatory light chain (RLC) of cardiac myosin is known to play a beneficial role in heart disease, but the idea of a phosphorylation-mediated reversal of a hypertrophic cardiomyopathy (HCM) phenotype is novel. Our previous studies on transgenic (Tg) HCM-RLC mice revealed that the D166V (Aspartate166 →Valine) mutation-induced changes in heart morphology and function coincided with largely reduced RLC phosphorylation in situ. In this paper, we hypothesized that the introduction of a constitutively phosphorylated Serine15 (S15D) into the hearts of D166V mice would prevent the development of a deleterious HCM phenotype. In support of this notion, MLCK-induced phosphorylation of D166V-mutated hearts was found to rescue some of their abnormal contractile properties. Tg-S15D-D166V mice were generated with the human cardiac RLC-S15D-D166V construct substituted for mouse cardiac RLC and were subjected to functional, structural, and morphological assessments. The results were compared with Tg-WT and Tg-D166V mice expressing the human ventricular RLC-WT or its D166V mutant, respectively. Echocardiography and invasive hemodynamic studies demonstrated significant improvements of intact heart function in S15D-D166V mice compared with D166V, with the systolic and diastolic indices reaching those monitored in WT mice. A largely reduced maximal tension and abnormally high myofilament Ca2+ sensitivity observed in D166V-mutated hearts were reversed in S15D-D166V mice. Low-angle X-ray diffraction study revealed that altered myofilament structures present in HCM-D166V mice were mitigated in S15D-D166V rescue mice. Finally, our collective results suggest that expression of pseudophosphorylated RLC in the hearts of HCM mice is sufficient to prevent the development of the pathological HCM phenotype.

  13. Changes in coronary sinus pH during dipyridamole stress in patients with hypertrophic cardiomyopathy.

    PubMed Central

    Elliott, P. M.; Rosano, G. M.; Gill, J. S.; Poole-Wilson, P. A.; Kaski, J. C.; McKenna, W. J.

    1996-01-01

    OBJECTIVES: The presence of angina pectoris and myocardial scarring in patients with hypertrophic cardiomyopathy (HCM) suggests that myocardial ischemia is a factor in the pathophysiology of the disease. The clinical evaluation of ischaemia is problematic in HCM as baseline electrocardiographic abnormalities are frequent and thallium-201 perfusion abnormalities correlate poorly with anginal symptoms. Coronary sinus pH measurement using a catheter mounted pH electrode is a validated sensitive technique for the detection of myocardial ischaemia. METHODS AND RESULTS: 11 patients with HCM and chest pain (eight men; mean (SD) (range) age 36 (11) (19-53) years) and six controls (two men; mean (SD) (range) age 49 (11) (31-62) years) with atypical pain and normal coronary angiograms were studied. Eight patients with HCM had baseline ST segment depression of > or = 1 mm and four had reversible perfusion defects during stress 201TI scintigraphy. A catheter mounted hydrogen ion sensitive electrode was introduced into the coronary sinus and pH monitored continuously during dipyridamole infusion (0.56 mg/kg over four min). The maximal change in coronary sinus pH during dipyridamole stress was greater in patients with HCM than in controls (0.082 (0.083) (0 to -0.275) v 0.005 (0.006) (0 to -0.012), P = 0.02). In six patients (four men; mean (SD) (range) age 29 (9) (19-40 years) the development of chest pain was associated with a gradual decline in coronary sinus pH (mean 0.123 (0.089)), peaking at 442 (106) s. There were no relations among left ventricular dimensions, maximal wall thickness, and maximum pH change. In patients with HCM there was a correlation between maximum pH change and maximum heart rate during dipyridamole infusion (r = 0.70, P = 0.02). CONCLUSION: This study provides further evidence that chest pain in patients with HCM is caused by myocardial ischaemia. The role of myocardial ischaemia in the pathophysiology of the disease remains to be determined but

  14. Clozapine in a patient with treatment-resistant schizophrenia and hypertrophic cardiomyopathy: a case report

    PubMed Central

    Sanchez, Asiel Yair Adan; Foster, Jessica J.; Plymen, Carla M.; Shergill, Sukhi

    2016-01-01

    Background There is currently limited experience in the initiation and maintenance of clozapine for treatment-resistant psychosis in adults with established structural heart disease. These complex patients require close supervision and liaison between colleagues. Here we present the successful experience of treating one such patient within our service and describe a monitoring plan to ensure that these treatments can be provided both safely and effectively. Case presentation A 36-year-old man with treatment-resistant schizophrenia and known hypertrophic cardiomyopathy (HCM) was admitted to a specialist unit for a trial of clozapine. His psychiatric illness was characterised by multimodal hallucinations and delusions combined with low mood and poor motivation. The diagnosis of HCM was made 3 years previously following a routine electrocardiogram (ECG), and he had remained asymptomatic throughout this time; there were concerns about the risk of initiating clozapine given his pre-existing cardiac condition. Baseline investigations were performed as per local guidelines prior to commencing clozapine; these were within normal limits other than a mildly raised troponin level of 54 ng/L (normal <16 ng/L), which was attributed to the HCM. In addition, baseline transthoracic echocardiography (TTE) was performed which showed no change in the structural heart disease in comparison with previous TTEs. Clozapine was started at 12.5 mg daily and up-titrated to 150 mg twice daily over 14 days as per our institute’s guidelines. The patient was monitored with regular testing of troponins, inflammatory markers and ECG. On day 18, the troponin level increased to 1371 ng/L. Creatine kinase and inflammatory markers remained stable. No changes in ECG or TTE were noted and the patient remained clinically asymptomatic. Cardiology opinion was sought and reported that the finding of an isolated elevated troponin was likely to reflect a ‘troponin leak’ in the context of increased

  15. Cardiac magnetic field map topology quantified by Kullback-Leibler entropy identifies patients with hypertrophic cardiomyopathy

    NASA Astrophysics Data System (ADS)

    Schirdewan, A.; Gapelyuk, A.; Fischer, R.; Koch, L.; Schütt, H.; Zacharzowsky, U.; Dietz, R.; Thierfelder, L.; Wessel, N.

    2007-03-01

    Hypertrophic cardiomyopathy (HCM) is a common primary inherited cardiac muscle disorder, defined clinically by the presence of unexplained left ventricular hypertrophy. The detection of affected patients remains challenging. Genetic testing is limited because only in 50%-60% of all HCM diagnoses an underlying mutation can be found. Furthermore, the disease has a varied clinical course and outcome, with many patients having little or no discernible cardiovascular symptoms, whereas others develop profound exercise limitation and recurrent arrhythmias or sudden cardiac death. Therefore prospective screening of HCM family members is strongly recommended. According to the current guidelines this includes serial echocardiographic and electrocardiographic examinations. In this study we investigated the capability of cardiac magnetic field mapping (CMFM) to detect patients suffering from HCM. We introduce for the first time a combined diagnostic approach based on map topology quantification using Kullback-Leibler (KL) entropy and regional magnetic field strength parameters. The cardiac magnetic field was recorded over the anterior chest wall using a multichannel-LT-SQUID system. CMFM was calculated based on a regular 36 point grid. We analyzed CMFM in patients with confirmed diagnosis of HCM (HCM, n =33, 43.8±13 years, 13 women, 20 men), a control group of healthy subjects (NORMAL, n =57, 39.6±8.9 years; 22 women and 35 men), and patients with confirmed cardiac hypertrophy due to arterial hypertension (HYP, n =42, 49.7±7.9 years, 15 women and 27 men). A subgroup analysis was performed between HCM patients suffering from the obstructive (HOCM, n =19) and nonobstructive (HNCM, n =14) form of the disease. KL entropy based map topology quantification alone identified HCM patients with a sensitivity of 78.8% and specificity of 86.9% (overall classification rate 84.8%). The combination of the KL parameters with a regional field strength parameter improved the overall

  16. Coronary microvascular ischemia in hypertrophic cardiomyopathy - a pixel-wise quantitative cardiovascular magnetic resonance perfusion study

    PubMed Central

    2014-01-01

    Background Microvascular dysfunction in HCM has been associated with adverse clinical outcomes. Advances in quantitative cardiovascular magnetic resonance (CMR) perfusion imaging now allow myocardial blood flow to be quantified at the pixel level. We applied these techniques to investigate the spectrum of microvascular dysfunction in hypertrophic cardiomyopathy (HCM) and to explore its relationship with fibrosis and wall thickness. Methods CMR perfusion imaging was undertaken during adenosine-induced hyperemia and again at rest in 35 patients together with late gadolinium enhancement (LGE) imaging. Myocardial blood flow (MBF) was quantified on a pixel-by-pixel basis from CMR perfusion images using a Fermi-constrained deconvolution algorithm. Regions-of-interest (ROI) in hypoperfused and hyperemic myocardium were identified from the MBF pixel maps. The myocardium was also divided into 16 AHA segments. Results Resting MBF was significantly higher in the endocardium than in the epicardium (mean ± SD: 1.25 ± 0.35 ml/g/min versus 1.20 ± 0.35 ml/g/min, P < 0.001), a pattern that reversed with stress (2.00 ± 0.76 ml/g/min versus 2.36 ± 0.83 ml/g/min, P < 0.001). ROI analysis revealed 11 (31%) patients with stress MBF lower than resting values (1.05 ± 0.39 ml/g/min versus 1.22 ± 0.36 ml/g/min, P = 0.021). There was a significant negative association between hyperemic MBF and wall thickness (β = −0.047 ml/g/min per mm, 95% CI: −0.057 to −0.038, P < 0.001) and a significantly lower probability of fibrosis in a segment with increasing hyperemic MBF (odds ratio per ml/g/min: 0.086, 95% CI: 0.078 to 0.095, P = 0.003). Conclusions Pixel-wise quantitative CMR perfusion imaging identifies a subgroup of patients with HCM that have localised severe microvascular dysfunction which may give rise to myocardial ischemia. PMID:25160568

  17. Constitutive phosphorylation of cardiac myosin regulatory light chain prevents development of hypertrophic cardiomyopathy in mice

    DOE PAGES

    Yuan, Chen-Ching; Muthu, Priya; Kazmierczak, Katarzyna; ...

    2015-06-29

    Myosin light chain kinase (MLCK)-dependent phosphorylation of the regulatory light chain (RLC) of cardiac myosin is known to play a beneficial role in heart disease, but the idea of a phosphorylation-mediated reversal of a hypertrophic cardiomyopathy (HCM) phenotype is novel. Our previous studies on transgenic (Tg) HCM-RLC mice revealed that the D166V (Aspartate166 →Valine) mutation-induced changes in heart morphology and function coincided with largely reduced RLC phosphorylation in situ. In this paper, we hypothesized that the introduction of a constitutively phosphorylated Serine15 (S15D) into the hearts of D166V mice would prevent the development of a deleterious HCM phenotype. In supportmore » of this notion, MLCK-induced phosphorylation of D166V-mutated hearts was found to rescue some of their abnormal contractile properties. Tg-S15D-D166V mice were generated with the human cardiac RLC-S15D-D166V construct substituted for mouse cardiac RLC and were subjected to functional, structural, and morphological assessments. The results were compared with Tg-WT and Tg-D166V mice expressing the human ventricular RLC-WT or its D166V mutant, respectively. Echocardiography and invasive hemodynamic studies demonstrated significant improvements of intact heart function in S15D-D166V mice compared with D166V, with the systolic and diastolic indices reaching those monitored in WT mice. A largely reduced maximal tension and abnormally high myofilament Ca2+ sensitivity observed in D166V-mutated hearts were reversed in S15D-D166V mice. Low-angle X-ray diffraction study revealed that altered myofilament structures present in HCM-D166V mice were mitigated in S15D-D166V rescue mice. Finally, our collective results suggest that expression of pseudophosphorylated RLC in the hearts of HCM mice is sufficient to prevent the development of the pathological HCM phenotype.« less

  18. [Atrial fibrillation in patients with obstructive hypertrophic cardiomyopathy: clinical characteristics and risk factors].

    PubMed

    Wu, X; Cui, H; Wang, J J; Xiao, M H; Lu, J; Zheng, X X; Guo, Y; Wang, S Y; Huang, X H

    2017-03-01

    Objective: To evaluate the clinical characteristics and risk factors for atrial fibrillation(AF)in patients with obstructive hypertrophic cardiomyopathy(OHCM). Methods: Patients with OHCM hospitalized in Fuwai Hospital from March 2011 to January 2016 were enrolled in the present study. Each patient underwent examinations including transthoracic echocardiography, body surface electrocardiograph or dynamic electrocardiogram (Holter). Cardiac troponin I (cTNI) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP)levels were tested and clinical profiles were collected.The subjects were divided into two groups (the AF group and non-AF group). Risk factors for AF in patients with OHCM were assessed by multivariate logistic regression analysis. Results: A total of 309 patients were evaluated in the study. Among them, 17.5%( 54/309) patients were with AF.Age[(51.2±10.1)years vs (43.1 ± 14.4)years], New York Heart Association class(NYHA class)(2.8±0.5 vs 2.6±0.6), disease duration[6.0(4.0, 10.0)years vs 3.0(1.0, 6.0)years], left atrial (LA) dimension[(45.1±7.0)mm vs(42.6 ± 7.4)mm]and NT-pro-BNP levels[2 007(1 565, 3 199)pmol/L vs 1 509(729, 2 921)pmol/L]in the AF group were significantly higher than those in the non-AF group (all P<0.05). Multivariate logistic regression analysis indicated that advanced age(OR=1.04, 95% CI 1.01-1.08, P<0.01), higher NYHA class(OR=2.00, 95% CI 1.08-3.70, P<0.05)and longer disease duration(OR=1.08, 95% CI 1.01-1.15, P<0.05)were independent risk factors for AF in patients with OHCM, in which advanced age(OR=1.05, 95% CI 1.02-1.09, P<0.01), higher NYHA class(OR=3.39, 95% CI 1.53-7.54, P<0.01), LA dimension(OR=1.06, 95% CI 1.01-1.12, P<0.05)and longer clinical course(OR=1.12, 95% CI 1.04-1.20, P<0.01)were associated with AF in male patients, and advanced age (OR=1.05, 95% CI 1.01-1.09, P<0.05)and longer disease duration(OR=1.14, 95% CI 1.01-1.28, P<0.01)were associated with AF in female patients when stratified by gender. Conclusion

  19. Combined effects of low-dose spironolactone and captopril therapy in a rat model of genetic hypertrophic cardiomyopathy.

    PubMed

    de Resende, Micheline Monteiro; Kriegel, Alison Jessica; Greene, Andrew Seth

    2006-12-01

    For several years, the severe side effects associated with the use of high doses of the aldosterone antagonist, spironolactone, limited its clinical use. Studies have recently shown efficacy and minimal side effects of low-dose spironolactone combined with standard therapy in the treatment of heart failure and hypertensive patients. The authors evaluated the effects of low-dose spironolactone alone or in combination with angiotensin-converting enzyme (ACE) inhibitors on the progression of left ventricular dysfunction and remodeling in a congenic rat model of hypertrophic cardiomyopathy. The congenic SS-16/Mcwi rats developed severe cardiac hypertrophy despite being normotensive even on high-salt diet. SS-16/Mcwi and SS/Mcwi rats were fed a low-salt (0.4% NaCl) diet and were treated with vehicle (CON), spironolactone (20 mg/kg/d subcutaneously), captopril (100 mg/kg/d drinking water), or both spironolactone and captopril for 4 weeks. Blood pressure, plasma peptides, cardiac fibrosis, and echocardiography measurements were evaluated. Spironolactone at a low dose had no effect on blood pressure, cardiac hypertrophy, and fibrosis in either strain. However, in combination with captopril, spironolactone decreased the cardiac hypertrophy more than captopril treatment alone. In the SS-16/Mcwi rats, the combined therapy significantly preserved the cardiac index when compared with control. These data indicate that the addition of low-dose spironolactone to captopril treatment was more effective in preventing the progression of heart hypertrophy and ventricular dysfunction in the SS-16/Mcwi than captopril alone. This study suggests that combined spironolactone and captopril therapy may be useful in the treatment of hypertrophic cardiomyopathy.

  20. Screening mutations in myosin binding protein C3 gene in a cohort of patients with Hypertrophic Cardiomyopathy

    PubMed Central

    2010-01-01

    Background MyBPC3 mutations are amongst the most frequent causes of hypertrophic cardiomyopathy, however, its prevalence varies between populations. They have been associated with mild and late onset disease expression. Our objectives were to establish the prevalence of MyBPC3 mutations and determine their associated clinical characteristics in our patients. Methods Screening by Single Strand Conformation Polymorphisms (SSCP) and sequencing of the fragments with abnormal motility of the MyBPC3 gene in 130 unrelated consecutive HCM index cases. Genotype-Phenotype correlation studies were done in positive families. Results 16 mutations were found in 20 index cases (15%): 5 novel [D75N, V471E, Q327fs, IVS6+5G>A (homozygous), and IVS11-9G>A] and 11 previously described [A216T, R495W, R502Q (2 families), E542Q (3 families), T957S, R1022P (2 families), E1179K, K504del, K600fs, P955fs and IVS29+5G>A]. Maximum wall thickness and age at time of diagnosis were similar to patients with MYH7 mutations [25(7) vs. 27(8), p = 0.16], [46(16) vs. 44(19), p = 0.9]. Conclusions Mutations in MyBPC3 are present in 15% of our hypertrophic cardiomyopathy families. Severe hypertrophy and early expression are compatible with the presence of MyBPC3 mutations. The genetic diagnosis not only allows avoiding clinical follow up of non carriers but it opens new possibilities that includes: to take preventive clinical decisions in mutation carriers than have not developed the disease yet, the establishment of genotype-phenotype relationship, and to establish a genetic diagnosis routine in patients with familial HCM. PMID:20433692

  1. Left ventricular chamber dilatation in hypertrophic cardiomyopathy: related variables and prognosis in patients with medical and surgical therapy.

    PubMed Central

    Seiler, C.; Jenni, R.; Vassalli, G.; Turina, M.; Hess, O. M.

    1995-01-01

    BACKGROUND--To determine the incidence and prognosis of left ventricular dilatation and systolic dysfunction in 139 patients with hypertrophic cardiomyopathy during long term follow up. METHODS--Left ventricular chamber dilatation and systolic dysfunction (both together referred to as left ventricular chamber dilatation) were determined echocardiographically. Chamber dilatation was defined as an increase in the left ventricular end diastolic diameter of > 2% per year combined with a decrease in midventricular systolic fractional shortening of > 2% per year of follow up [10.3 (SD 6) years]. The predictive value for left ventricular chamber dilatation of clinical, invasive, and echocardiographic variables and its prognosis were assessed. RESULTS--In 119 of 139 individuals (86%), left ventricular chamber size and systolic function remained stable (group 1), and in 20/139 patients (14%) left ventricular chamber dilatation occurred during follow up (group 2). At baseline examination, symptoms such as dyspnoea and syncope occurred less often in group 1 than in group 2; New York Heart Association classification was lower in group 1 than in group 2 (P = 0.001). Left ventricular mass index relative to sex specific normal values was increased by 18% in group 1 and by 41% in group 2 (P = 0.04). Cumulative survival rates were slightly although not significantly higher in group 1 than in group 2. Event-free survival was significantly higher in group 1 than in group 2 (P < 0.05). CONCLUSIONS--(1) The development of left ventricular chamber dilatation and systolic dysfunction in hypertrophic cardiomyopathy occurs in approximately 1.5% of the patients per year. (2) Factors associated with left ventricular dilatation are dyspnoea, syncope, a higher functional classification, and a higher degree of left ventricular hypertrophy. (3) Patients with chamber dilatation have a worse prognosis than those without, particularly regarding quality of life. PMID:8562235

  2. Microarray analysis of active cardiac remodeling genes in a familial hypertrophic cardiomyopathy mouse model rescued by a phospholamban knockout

    PubMed Central

    Rajan, Sudarsan; Pena, James R.; Jegga, Anil G.; Aronow, Bruce J.; Wolska, Beata M.

    2013-01-01

    Familial hypertrophic cardiomyopathy (FHC) is a disease characterized by ventricular hypertrophy, fibrosis, and aberrant systolic and/or diastolic function. Our laboratories have previously developed two mouse models that affect cardiac performance. One mouse model encodes an FHC-associated mutation in α-tropomyosin: Glu → Gly at amino acid 180, designated as Tm180. These mice display a phenotype that is characteristic of FHC, including severe cardiac hypertrophy with fibrosis and impaired physiological performance. The other model was a gene knockout of phospholamban (PLN KO), a regulator of calcium uptake in the sarcoplasmic reticulum of cardiomyocytes; these hearts exhibit hypercontractility with no pathological abnormalities. Previous work in our laboratories shows that when mice were genetically crossed between the PLN KO and Tm180, the progeny (PLN KO/Tm180) display a rescued hypertrophic phenotype with improved morphology and cardiac function. To understand the changes in gene expression that occur in these models undergoing cardiac remodeling (Tm180, PLN KO, PLN KO/Tm180, and nontransgenic control mice), we conducted microarray analyses of left ventricular tissue at 4 and 12 mo of age. Expression profiling reveals that 1,187 genes changed expression in direct response to the three genetic models. With these 1,187 genes, 11 clusters emerged showing normalization of transcript expression in the PLN KO/Tm180 hearts. In addition, 62 transcripts are highly involved in suppression of the hypertrophic phenotype. Confirmation of the microarray analysis was conducted by quantitative RT-PCR. These results provide insight into genes that alter expression during cardiac remodeling and are active during modulation of the cardiomyopathic phenotype. PMID:23800848

  3. Gene expression patterns in transgenic mouse models of hypertrophic cardiomyopathy caused by mutations in myosin regulatory light chain☆

    PubMed Central

    Huang, Wenrui; Kazmierczak, Katarzyna; Zhou, Zhiqun; Aguiar-Pulido, Vanessa; Narasimhan, Giri; Szczesna-Cordary, Danuta

    2017-01-01

    Using microarray and bioinformatics, we examined the gene expression profiles in transgenic mouse hearts expressing mutations in the myosin regulatory light chain shown to cause hypertrophic cardiomyopathy (HCM). We focused on two malignant RLC-mutations, Arginine 58→Glutamine (R58Q) and Aspartic Acid 166 → Valine (D166V), and one benign, Lysine 104 → Glutamic Acid (K104E)-mutation. Datasets of differentially expressed genes for each of three mutants were compared to those observed in wild-type (WT) hearts. The changes in the mutant vs. WT samples were shown as fold-change (FC), with stringency FC ≥ 2. Based on the gene profiles, we have identified the major signaling pathways that underlie the R58Q-, D166V- and K104E-HCM phenotypes. The correlations between different genotypes were also studied using network-based algorithms. Genes with strong correlations were clustered into one group and the central gene networks were identified for each HCM mutant. The overall gene expression patterns in all mutants were distinct from the WT profiles. Both malignant mutations shared certain classes of genes that were up or downregulated, but most similarities were noted between D166V and K104E mice, with R58Q hearts showing a distinct gene expression pattern. Our data suggest that all three HCM mice lead to cardiomyopathy in a mutation-specific manner and thus develop HCM through diverse mechanisms. PMID:26906074

  4. Hypertrophic obstructive cardiomyopathy in combination with anomalous insertion of papillary muscle directly into anterior mitral leaflet and "sawfish" systolic narrowing of the left anterior descending coronary artery.

    PubMed

    Taşdemir, O; Küçükaksu, D S; Kural, T; Bayazit, K

    1994-01-01

    This report describes an unusual case of subaortic stenosis in which hypertrophic obstructive cardiomyopathy was found in combination with both anomalous insertion of papillary muscle directly into the anterior mitral leaflet and "sawfish" systolic narrowing of the left anterior descending coronary artery. Definitive diagnosis was made on operation. We freed the left anterior descending coronary artery by incising the muscular bridge, resected both papillary muscles, and replaced the mitral valve.

  5. Hypertrophic obstructive cardiomyopathy in combination with anomalous insertion of papillary muscle directly into anterior mitral leaflet and "sawfish" systolic narrowing of the left anterior descending coronary artery.

    PubMed Central

    Taşdemir, O; Küçükaksu, D S; Kural, T; Bayazit, K

    1994-01-01

    This report describes an unusual case of subaortic stenosis in which hypertrophic obstructive cardiomyopathy was found in combination with both anomalous insertion of papillary muscle directly into the anterior mitral leaflet and "sawfish" systolic narrowing of the left anterior descending coronary artery. Definitive diagnosis was made on operation. We freed the left anterior descending coronary artery by incising the muscular bridge, resected both papillary muscles, and replaced the mitral valve. Images PMID:7888810

  6. Hypertrophic and dilated cardiomyopathy: four decades of basic research on muscle lead to potential therapeutic approaches to these devastating genetic diseases.

    PubMed

    Spudich, James A

    2014-03-18

    With the advent of technologies to obtain the complete sequence of the human genome in a cost-effective manner, this decade and those to come will see an exponential increase in our understanding of the underlying genetics that lead to human disease. And where we have a deep understanding of the biochemical and biophysical basis of the machineries and pathways involved in those genetic changes, there are great hopes for the development of modern therapeutics that specifically target the actual machinery and pathways altered by individual mutations. Prime examples of such a genetic disease are those classes of hypertrophic and dilated cardiomyopathy that result from single amino-acid substitutions in one of several of the proteins that make up the cardiac sarcomere or from the truncation of myosin binding protein C. Hypertrophic cardiomyopathy alone affects ∼1 in 500 individuals, and it is the leading cause of sudden cardiac death in young adults. Here I describe approaches to understand the molecular basis of the alterations in power output that result from these mutations. Small molecules binding to the mutant sarcomeric protein complex should be able to mitigate the effects of hypertrophic and dilated cardiomyopathy mutations at their sources, leading to possible new therapeutic approaches for these genetic diseases.

  7. Hypertrophic and Dilated Cardiomyopathy: Four Decades of Basic Research on Muscle Lead to Potential Therapeutic Approaches to These Devastating Genetic Diseases

    PubMed Central

    Spudich, James A.

    2014-01-01

    With the advent of technologies to obtain the complete sequence of the human genome in a cost-effective manner, this decade and those to come will see an exponential increase in our understanding of the underlying genetics that lead to human disease. And where we have a deep understanding of the biochemical and biophysical basis of the machineries and pathways involved in those genetic changes, there are great hopes for the development of modern therapeutics that specifically target the actual machinery and pathways altered by individual mutations. Prime examples of such a genetic disease are those classes of hypertrophic and dilated cardiomyopathy that result from single amino-acid substitutions in one of several of the proteins that make up the cardiac sarcomere or from the truncation of myosin binding protein C. Hypertrophic cardiomyopathy alone affects ∼1 in 500 individuals, and it is the leading cause of sudden cardiac death in young adults. Here I describe approaches to understand the molecular basis of the alterations in power output that result from these mutations. Small molecules binding to the mutant sarcomeric protein complex should be able to mitigate the effects of hypertrophic and dilated cardiomyopathy mutations at their sources, leading to possible new therapeutic approaches for these genetic diseases. PMID:24655499

  8. Treating a Structural Heart Disease Using a Non-structural Approach: Role of Cardiac Pacing in Hypertrophic Cardiomyopathy

    PubMed Central

    Albano, Bernard Benjamin P.; Fadreguilan, Erdie C.; Chua, Jeffrey M.; Ho, James; Medrano, Ana Beatriz

    2017-01-01

    Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease characterized by a thickened non-dilated ventricle in the absence of another cardiac or systemic condition. Its most important hemodynamic consequence is left ventricular outflow tract (LVOT) obstruction. The primary management strategy of this condition is surgical septal myectomy, but an acceptable alternative treatment in patients who are not suitable for (or who refuse) surgery is alcohol septal ablation (ASA). However, in patients with unfavorable coronary anatomy which precludes ASA (i.e. absence of major septal perforator branch of the left anterior descending (LAD) artery), another reasonable option is dual chamber pacemaker implantation to decrease LVOT outflow gradient. A 77-year-old female, known hypertensive, diabetic with a history of coronary artery disease, presented with 1-week history of worsening chest pain and shortness of breath. She was admitted as a case of acute coronary syndrome and pneumonia. On workup, 2DED revealed hypertrophic obstructive cardiomyopathy (HOCM) with a demonstrated systolic anterior motion (SAM) of the mitral valve with a peak instantaneous gradient of 194 mm Hg across the basal LV cavity. The patient refused surgical myectomy, and ASA was the preferred treatment option. On coronary angiography, there was an incidental finding of absent major septal perforator branch of the LAD coronary artery, rendering her unsuitable for septal ablation. She was referred to electrophysiology for evaluation. She underwent dual chamber pacemaker implantation and documented significant decrease in the peak instantaneous gradient from 194 to 37 mm Hg, with complete obliteration of SAM and improvement in overall wall motion. She remained stable and asymptomatic after pacemaker insertion until her recent outpatient follow-up (1 year after implantation). We present a case of HCM with congenitally absent major septal perforator branch coronary artery treated with

  9. The Hypertrophic Cardiomyopathy Myosin Mutation R453C Alters ATP Binding and Hydrolysis of Human Cardiac β-Myosin*

    PubMed Central

    Bloemink, Marieke; Deacon, John; Langer, Stephen; Vera, Carlos; Combs, Ariana; Leinwand, Leslie; Geeves, Michael A.

    2014-01-01

    The human hypertrophic cardiomyopathy mutation R453C results in one of the more severe forms of the myopathy. Arg-453 is found in a conserved surface loop of the upper 50-kDa domain of the myosin motor domain and lies between the nucleotide binding pocket and the actin binding site. It connects to the cardiomyopathy loop via a long α-helix, helix O, and to Switch-2 via the fifth strand of the central β-sheet. The mutation is, therefore, in a position to perturb a wide range of myosin molecular activities. We report here the first detailed biochemical kinetic analysis of the motor domain of the human β-cardiac myosin carrying the R453C mutation. A recent report of the same mutation (Sommese, R. F., Sung, J., Nag, S., Sutton, S., Deacon, J. C., Choe, E., Leinwand, L. A., Ruppel, K., and Spudich, J. A. (2013) Proc. Natl. Acad. Sci. U.S.A. 110, 12607–12612) found reduced ATPase and in vitro motility but increased force production using an optical trap. Surprisingly, our results show that the mutation alters few biochemical kinetic parameters significantly. The exceptions are the rate constants for ATP binding to the motor domain (reduced by 35%) and the ATP hydrolysis step/recovery stroke (slowed 3-fold), which could be the rate-limiting step for the ATPase cycle. Effects of the mutation on the recovery stroke are consistent with a perturbation of Switch-2 closure, which is required for the recovery stroke and the subsequent ATP hydrolysis. PMID:24344137

  10. The flexibility of two tropomyosin mutants, D175N and E180G, that cause hypertrophic cardiomyopathy

    SciTech Connect

    Li, Xiaochuan; Suphamungmee, Worawit; Janco, Miro; Geeves, Michael A.; Marston, Steven B.; Fischer, Stefan; Lehman, William

    2012-08-03

    Highlights: Black-Right-Pointing-Pointer Well-known tropomyosin mutants, D175N and E180G are linked to cardiomyopathies. Black-Right-Pointing-Pointer The structural mechanics of D175N and E180G tropomyosins have been investigated. Black-Right-Pointing-Pointer D175N and E180G mutations increase both local and global tropomyosin flexibility. Black-Right-Pointing-Pointer In muscle, this increased flexibility will enhance myosin interactions on actin. Black-Right-Pointing-Pointer Extra myosin interaction can alter cardiac Ca{sup 2+}-switching, leading to dysfunction. -- Abstract: Point mutations targeting muscle thin filament proteins are the cause of a number of cardiomyopathies. In many cases, biological effects of the mutations are well-documented, whereas their structural and mechanical impact on filament assembly and regulatory function is lacking. In order to elucidate molecular defects leading to cardiac dysfunction, we have examined the structural mechanics of two tropomyosin mutants, E180G and D175N, which are associated with hypertrophic cardiomyopathy (HCM). Tropomyosin is an {alpha}-helical coiled-coil dimer which polymerizes end-to-end to create an elongated superhelix that wraps around F-actin filaments of muscle and non-muscle cells, thus modulating the binding of other actin-binding proteins. Here, we study how flexibility changes in the E180G and D175N mutants might affect tropomyosin binding and regulatory motion on F-actin. Electron microscopy and Molecular Dynamics simulations show that E180G and D175N mutations cause an increase in bending flexibility of tropomyosin both locally and globally. This excess flexibility is likely to increase accessibility of the myosin-binding sites on F-actin, thus destabilizing the low-Ca{sup 2+} relaxed-state of cardiac muscle. The resulting imbalance in the on-off switching mechanism of the mutants will shift the regulatory equilibrium towards Ca{sup 2+}-activation of cardiac muscle, as is observed in affected

  11. Cardiomyopathy

    MedlinePlus

    Cardiomyopathy is the name for diseases of the heart muscle. These diseases enlarge your heart muscle or ... tissue. Some people live long, healthy lives with cardiomyopathy. Some people don't even realize they have ...

  12. Evaluation of a motion artifacts removal approach on breath-hold cine-magnetic resonance images of hypertrophic cardiomyopathy subjects

    NASA Astrophysics Data System (ADS)

    Betancur, Julián.; Simon, Antoine; Schnell, Frédéric; Donal, Erwan; Hernández, Alfredo; Garreau, Mireille

    2013-11-01

    The acquisition of ECG-gated cine magnetic resonance images of the heart is routinely performed in apnea in order to suppress the motion artifacts caused by breathing. However, many factors including the 2D nature of the acquisition and the use of di erent beats to acquire the multiple-view cine images, cause this kind of artifacts to appear. This paper presents the qualitative evaluation of a method aiming to remove motion artifacts in multipleview cine images acquired on patients with hypertrophic cardiomyopathy diagnosis. The approach uses iconic registration to reduce for in-plane artifacts in long-axis-view image stacks and in-plane and out-of-plane motion artifacts in sort-axis-view image stack. Four similarity measures were evaluated: the normalized correlation, the normalized mutual information, the sum of absolute voxel di erences and the Slomka metric proposed by Slomka et al. The qualitative evaluation assessed the misalignment of di erent anatomical structures of the left ventricle as follows: the misalignment of the interventricular septum and the lateral wall for short-axis-view acquisitions and the misalignment between the short-axis-view image and long-axis-view images. Results showed the correction using the normalized correlation as the most appropriated with an 80% of success.

  13. Screening Mutations of MYBPC3 in 114 Unrelated Patients with Hypertrophic Cardiomyopathy by Targeted Capture and Next-generation Sequencing.

    PubMed

    Liu, Xuxia; Jiang, Tengyong; Piao, Chunmei; Li, Xiaoyan; Guo, Jun; Zheng, Shuai; Zhang, Xiaoping; Cai, Tao; Du, Jie

    2015-06-19

    Hypertrophic cardiomyopathy (HCM) is a major cause of sudden cardiac death. Mutations in the MYBPC3 gene represent the cause of HCM in ~35% of patients with HCM. However, genetic testing in clinic setting has been limited due to the cost and relatively time-consuming by Sanger sequencing. Here, we developed a HCM Molecular Diagnostic Kit enabling ultra-low-cost targeted gene resequencing in a large cohort and investigated the mutation spectrum of MYBPC3. In a cohort of 114 patients with HCM, a total of 20 different mutations (8 novel and 12 known mutations) of MYBPC3 were identified from 25 patients (21.9%). We demonstrated that the power of targeted resequencing in a cohort of HCM patients, and found that MYBPC3 is a common HCM-causing gene in Chinese patients. Phenotype-genotype analyses showed that the patients with double mutations (n = 2) or premature termination codon mutations (n = 12) showed more severe manifestations, compared with patients with missense mutations (n = 11). Particularly, we identified a recurrent truncation mutation (p.Y842X) in four unrelated cases (4/25, 16%), who showed severe phenotypes, and suggest that the p.Y842X is a frequent mutation in Chinese HCM patients with severe phenotypes.

  14. Rapidly Progressive Hypertrophic Cardiomyopathy in an Infant with Noonan syndrome with multiple Lentigines. Palliative Treatment with a Rapamycin Analog

    PubMed Central

    Hahn, Andreas; Lauriol, Jessica; Thul, Josef; Behnke-Hall, Kachina; Logeswaran, Tushiha; Schänzer, Anne; Böğürcü, Nuray; Garvalov, Boyan K.; Zenker, Martin; Gelb, Bruce D.; von Gerlach, Susanne; Kandolf, Reinhard; Kontaridis, Maria I.; Schranz, Dietmar

    2015-01-01

    Noonan syndrome with multiple lentigines (NSML) frequently manifests with hypertrophic cardiomyopathy (HCM). Recently, it was demonstrated that mTOR inhibition reverses HCM in NSML mice. We report for the first time on the effects of treatment with a rapamycin analog in an infant with LS and a malignant form of HCM. In the boy, progressive HCM was diagnosed during the first week of life and diagnosis of NSML was established at age 20 weeks by showing a heterozygous Q510E mutation in the PTPN11 gene. Immunoblotting with antibodies against pERK, pAkt, and pS6RP in fibroblasts demonstrated reduced RAS/MAPK and enhanced Akt/mTOR pathway activities. Because of the patient’s critical condition, everolimus therapy was started at age 24 weeks and continued until heart transplantation at age 36 weeks. Prior to surgery, heart failure improved from NYHA stage IV to II and brain natriuretic peptide values decreased from 9600 to <1000 pg/ml, but no reversal of cardiac hypertrophy was observed. Examination of the explanted heart revealed severe hypertrophy and myofiber disarray with extensive perivascular fibrosis. These findings provide evidence that Akt/mTOR activity is enhanced in NSML with HCM and suggest that rapamycin treatment could be principally feasible for infantile NSML. But the preliminary experiences made in this single patient indicate that therapy should start early to prevent irreversible cardiac remodelling. PMID:25708222

  15. Assessment of left ventricular longitudinal function in cats with subclinical hypertrophic cardiomyopathy using tissue Doppler imaging and speckle tracking echocardiography

    PubMed Central

    SUGIMOTO, Keisuke; FUJII, Yoko; SUNAHARA, Hiroshi; AOKI, Takuma

    2015-01-01

    Hypertrophic cardiomyopathy (HCM) in cats is characterized by concentric left ventricular (LV) hypertrophy and both diastolic and systolic dysfunction. Although impaired cardiac function detected by tissue Doppler imaging (TDI) in cats with HCM was previously reported, reference ranges of TDI in normal cats and cats with HCM have been reported as widely variable. Two-dimensional speckle tracking echocardiography (STE) was useful for assessment of cardiac function in human patients with HCM, but clinical utility was not known in cats. The aim of this study was to assess global and segmental LV myocardial function using STE in cats with HCM whose TDI variables were within the reference range. A total of 35 cats of different breeds were enrolled in this study. The HCM group (n=22) was cats diagnosed as HCM without left atrial enlargement and with normal TDI measurements. HCM cats were further divided into a segmental hypertrophy (S-HCM) group and a diffuse hypertrophy (D-HCM) group. The control group consisted of 13 clinically healthy cats. No cats in any group showed any clinical symptoms. Conventional echocardiography, TDI, and global and segmental STE indices were evaluated and compared between groups. Only the longitudinal strain rate during early diastole was significantly decreased in both HCM groups, even in all segments including those without hypertrophy in S-HCM group. This study suggests that STE parameters are the more sensitive variables compared with conventional TDI parameters to detect early myocardial diastolic dysfunction in cats with HCM. PMID:25877405

  16. Assessment of left ventricular longitudinal function in cats with subclinical hypertrophic cardiomyopathy using tissue Doppler imaging and speckle tracking echocardiography.

    PubMed

    Sugimoto, Keisuke; Fujii, Yoko; Sunahara, Hiroshi; Aoki, Takuma

    2015-09-01

    Hypertrophic cardiomyopathy (HCM) in cats is characterized by concentric left ventricular (LV) hypertrophy and both diastolic and systolic dysfunction. Although impaired cardiac function detected by tissue Doppler imaging (TDI) in cats with HCM was previously reported, reference ranges of TDI in normal cats and cats with HCM have been reported as widely variable. Two-dimensional speckle tracking echocardiography (STE) was useful for assessment of cardiac function in human patients with HCM, but clinical utility was not known in cats. The aim of this study was to assess global and segmental LV myocardial function using STE in cats with HCM whose TDI variables were within the reference range. A total of 35 cats of different breeds were enrolled in this study. The HCM group (n=22) was cats diagnosed as HCM without left atrial enlargement and with normal TDI measurements. HCM cats were further divided into a segmental hypertrophy (S-HCM) group and a diffuse hypertrophy (D-HCM) group. The control group consisted of 13 clinically healthy cats. No cats in any group showed any clinical symptoms. Conventional echocardiography, TDI, and global and segmental STE indices were evaluated and compared between groups. Only the longitudinal strain rate during early diastole was significantly decreased in both HCM groups, even in all segments including those without hypertrophy in S-HCM group. This study suggests that STE parameters are the more sensitive variables compared with conventional TDI parameters to detect early myocardial diastolic dysfunction in cats with HCM.

  17. Screening Mutations of MYBPC3 in 114 Unrelated Patients with Hypertrophic Cardiomyopathy by Targeted Capture and Next-generation Sequencing

    PubMed Central

    Liu, Xuxia; Jiang, Tengyong; Piao, Chunmei; Li, Xiaoyan; Guo, Jun; Zheng, Shuai; Zhang, Xiaoping; Cai, Tao; Du, Jie

    2015-01-01

    Hypertrophic cardiomyopathy (HCM) is a major cause of sudden cardiac death. Mutations in the MYBPC3 gene represent the cause of HCM in ~35% of patients with HCM. However, genetic testing in clinic setting has been limited due to the cost and relatively time-consuming by Sanger sequencing. Here, we developed a HCM Molecular Diagnostic Kit enabling ultra-low-cost targeted gene resequencing in a large cohort and investigated the mutation spectrum of MYBPC3. In a cohort of 114 patients with HCM, a total of 20 different mutations (8 novel and 12 known mutations) of MYBPC3 were identified from 25 patients (21.9%). We demonstrated that the power of targeted resequencing in a cohort of HCM patients, and found that MYBPC3 is a common HCM-causing gene in Chinese patients. Phenotype-genotype analyses showed that the patients with double mutations (n = 2) or premature termination codon mutations (n = 12) showed more severe manifestations, compared with patients with missense mutations (n = 11). Particularly, we identified a recurrent truncation mutation (p.Y842X) in four unrelated cases (4/25, 16%), who showed severe phenotypes, and suggest that the p.Y842X is a frequent mutation in Chinese HCM patients with severe phenotypes. PMID:26090888

  18. Myocardial contractile and metabolic properties of familial hypertrophic cardiomyopathy caused by cardiac troponin I gene mutations: a simulation study.

    PubMed

    Wu, Bo; Wang, Longhui; Liu, Qian; Luo, Qingming

    2012-01-01

    Familial hypertrophic cardiomyopathy (FHC) is an inherited disease that is caused by sarcomeric protein gene mutations. The mechanism by which these mutant proteins cause disease is uncertain. Experimentally, cardiac troponin I (CTnI) gene mutations mainly alter myocardial performance via increases in the Ca(2+) sensitivity of cardiac contractility. In this study, we used an integrated simulation that links electrophysiology, contractile activity and energy metabolism of the myocardium to investigate alterations in myocardial contractile function and energy metabolism regulation as a result of increased Ca(2+) sensitivity in CTnI mutations. Simulation results reproduced the following typical features of FHC: (1) slower relaxation (diastolic dysfunction) caused by prolonged [Ca(2+)](i) and force transients; (2) higher energy consumption with the increase in Ca(2+) sensitivity; and (3) reduced fatty acid oxidation and enhanced glucose utilization in hypertrophied heart metabolism. Furthermore, the simulation indicated that in conditions of high energy consumption (that is, more than an 18.3% increase in total energy consumption), the myocardial energetic metabolic network switched from a net consumer to a net producer of lactate, resulting in a low coupling of glucose oxidation to glycolysis, which is a common feature of hypertrophied hearts. This study provides a novel systematic myocardial contractile and metabolic analysis to help elucidate the pathogenesis of FHC and suggests that the alterations in resting heart energy supply and demand could contribute to disease progression.

  19. Short-limb dwarfism and hypertrophic cardiomyopathy in a patient with paternal isodisomy 14: 45,XYidic(14)(p11)

    SciTech Connect

    Walter, C.A.; Moore, C.M.; Kaye, C.I.

    1996-11-11

    Uniparental disomy (UPD) has been shown to result in specific disorders either due to imprinting and/or homozygosity of mutant alleles. Here we present the findings in a child with paternal UPD14. Ultrasound evaluation was performed at 30 weeks of gestation because of abnormally large uterine size. Pertinent ultrasound findings included polyhydramnios, short limbs, abnormal position of hands, small thorax, and nonvisualization of the fetal stomach. Postnatally the infant was found to have a low birth weight, short birth length, contractures, short limbs, and a small thorax with upslanting ribs. Assisted ventilation and gastrostomy were required. At age 6 months, the infant required hospitalization for hypertrophic cardiomyopathy which responded to Atenolol{reg_sign}. Initial cytogenetic studies demonstrated an apparently balanced de novo Robertsonian translocation involving chromosomes 14 and a karyotype designation of 45,XY,t(14q14q). No indication of mosaicism for trisomy 14 was observed in metaphase spreads prepared from peripheral blood lymphocytes or skin-derived fibroblasts. C-band and fluorescence in situ hybridization results demonstrated that the chromosome was dicentric. DNA analyses showed paternal uniparental isodisomy for chromosome 14. Based on the cytogenetic and DNA results a final karyotype designation of 45,XY,idic(14)(p11) was assigned to this infant with paternal isodisomy of chromosome 14. 41 refs., 5 figs., 2 tabs.

  20. A Pregnancy with Severe Hypertrophic Obstructive Cardiomyopathy after Surgery for an Implantable Cardioverter Defibrillator: A Case Report and Literature Review

    PubMed Central

    Mitsui, Takashi; Ejiri, Kentaro; Hayata, Kei; Ito, Hiroshi; Hiramatsu, Yuji

    2016-01-01

    Hypertrophic obstructive cardiomyopathy (HOCM) is cardiac hypertrophy of ventricular myocardium with left ventricular outflow tract obstruction. We report a pregnancy with HOCM after defibrillator implantation surgery. The patient was a 33-year-old nulligravida and was categorized as New York Heart Association class II. Her brain natriuretic peptide (BNP) level was 724.6 pg/dL at preconception. She received careful pregnancy management. However, because frequent uterine contractions were observed at 25 weeks and 6 days of pregnancy, she was hospitalized, and magnesium sulfate was started as a tocolytic agent. At 27 weeks and 5 days of pregnancy, she had respiratory discomfort and orthopnea with a sudden decrease in peripheral oxygen saturation. Cardiac ultrasonography showed a worsened condition of HOCM and her BNP level was 1418.0 pg/mL. We performed an emergent cesarean section and she delivered a boy weighing 999 g. The Apgar score was 8 and 9 points at 1 and 5 minutes, respectively. The mother's heart failure quickly improved after birth and she was discharged at 10 days postoperatively. Fluctuations in circulatory dynamics during pregnancy may sometimes exacerbate heart disease. Therefore, the risks should be fully explained and careful assessment of cardiac function should be performed during pregnancy in patients with severe HOCM. PMID:27830098

  1. Impact of Cryoballoon Ablation in Hypertrophic Cardiomyopathy-related Heart Failure due to Paroxysmal Atrial Fibrillation. A Comparative Case Series

    PubMed Central

    Maagh, Petra; Plehn, Gunnar; Christoph, Arnd; Oernek, Ahmet; Meissner, Axel

    2016-01-01

    Background: Atrial fibrillation (AF) represents a turning point in hypertrophic cardiomyopathy (HCM). Pulmonary Vein Isolation (PVI) with Radiofrequency Catheter Ablation (RFCA) is accepted to be successful in restoring sinus rhythm (SR) in HCM patients. The efficacy of cryoballoon (CB) therapy in HCM patients has not been studied so far. Methods: 166 patients with AF underwent PVI with CB technology in our single center between 1/2012 and 12/2015. To evaluate the efficacy of the CB therapy in HCM patients, we compared their clinical outcome with those in “Non-HCM” AF patients in a 3 and 6 months follow-up. Results: Out of 166 AF patients (65.7% paroxysmal AF, PAF), 4 patients had HCM and PAF (young males < 50 years). During the blanking period, 26 patients (15.8%) suffered from AF recurrence (11.0% PAF), including all HCM patients. The 6 months follow up of “Non-HCM” AF patients showed acceptable results (80% stable SR), whereas the HCM patients remained AF. In Conclusion: Even if the CB provides advantages, the single device cannot be recommended in HCM patients because of early AF recurrences. Anyway, because of the specific hemodynamic changes in HCM patients with AF, ablation should be sought in an early state of its occurrence, then, however, preferably with RFCA. PMID:27647995

  2. Kinetics of a single cross-bridge in familial hypertrophic cardiomyopathy heart muscle measured by reverse Kretschmann fluorescence

    NASA Astrophysics Data System (ADS)

    Mettikolla, Prasad; Calander, Nils; Luchowski, Rafal; Gryczynski, Ignacy; Gryczynski, Zygmunt; Borejdo, Julian

    2010-01-01

    Familial hypertrophic cardiomyopathy (FHC) is a serious heart disease that often leads to a sudden cardiac death of young athletes. It is believed that the alteration of the kinetics of interaction between actin and myosin causes FHC by making the heart to pump blood inefficiently. We set out to check this hypothesis ex vivo. During contraction of heart muscle, a myosin cross-bridge imparts periodic force impulses to actin. The impulses are analyzed by fluorescence correlation spectroscopy (FCS) of fluorescently labeled actin. To minimize observation volume and background fluorescence, we carry out FCS measurements in surface plasmon coupled emission mode in a reverse Kretschmann configuration. Fluorescence is a result of near-field coupling of fluorophores excited in the vicinity of the metal-coated surface of a coverslip with the surface plasmons propagating in the metal. Surface plasmons decouple on opposite sides of the metal film and emit in a directional manner as far-field p-polarized radiation. We show that the rate of changes of orientation is significantly faster in contracting cardiac myofibrils of transgenic mice than wild type. These results are consistent with the fact that mutated heart muscle myosin translates actin faster in in vitro motility assays.

  3. Molecular consequences of the R453C hypertrophic cardiomyopathy mutation on human β-cardiac myosin motor function

    PubMed Central

    Sommese, Ruth F.; Sung, Jongmin; Nag, Suman; Sutton, Shirley; Deacon, John C.; Choe, Elizabeth; Leinwand, Leslie A.; Ruppel, Kathleen; Spudich, James A.

    2013-01-01

    Cardiovascular disorders are the leading cause of morbidity and mortality in the developed world, and hypertrophic cardiomyopathy (HCM) is among the most frequently occurring inherited cardiac disorders. HCM is caused by mutations in the genes encoding the fundamental force-generating machinery of the cardiac muscle, including β-cardiac myosin. Here, we present a biomechanical analysis of the HCM-causing mutation, R453C, in the context of human β-cardiac myosin. We found that this mutation causes a ∼30% decrease in the maximum ATPase of the human β-cardiac subfragment 1, the motor domain of myosin, and a similar percent decrease in the in vitro velocity. The major change in the R453C human β-cardiac subfragment 1 is a 50% increase in the intrinsic force of the motor compared with wild type, with no appreciable change in the stroke size, as observed with a dual-beam optical trap. These results predict that the overall force of the ensemble of myosin molecules in the muscle should be higher in the R453C mutant compared with wild type. Loaded in vitro motility assay confirms that the net force in the ensemble is indeed increased. Overall, this study suggests that the R453C mutation should result in a hypercontractile state in the heart muscle. PMID:23798412

  4. Impediments to DNA testing and cascade screening for hypertrophic cardiomyopathy and Long QT syndrome: a qualitative study of patient experiences.

    PubMed

    Smart, Andrew

    2010-12-01

    This paper reports data from a qualitative study of patient experiences of DNA testing and cascade screening for hypertrophic cardiomyopathy and long QT syndrome, cardiac conditions that place sufferers at risk of sudden death. The paper particularly focuses on potential impediments to testing and screening. Semi-structured interviews were undertaken with a purposive sample of 27 people in the UK who had undergone testing. In the context of the uncertainties that can characterize experiences of these disorders, the majority of participants in this sample embraced testing and screening as a way of providing health information for themselves or their relatives (particularly children). There was nevertheless evidence of ambivalence about the value and impact of the DNA test information which could influence participants' dispositions toward testing, and play into dilemmas about family communication. Other concerns arose in relation to communicating about these disorders, decisions to involve elderly relatives and pressures relating to family responsibility. The evidence of ambivalence provides insight into why some people may be resistant to testing, screening and sharing information. The findings about communication processes indicate potential areas of concern for the cascading process.

  5. Left ventricular wall thickness in patients with hypertrophic cardiomyopathy: a comparison between cardiac magnetic resonance imaging and echocardiography.

    PubMed

    Corona-Villalobos, Celia P; Sorensen, Lars L; Pozios, Iraklis; Chu, Linda; Eng, John; Abraham, Maria Roselle; Abraham, Theodore P; Kamel, Ihab R; Zimmerman, Stefan L

    2016-06-01

    We assessed whether cardiac MRI (CMR) and echocardiography (echo) have significant differences measuring left ventricular (LV) wall thickness (WT) in hypertrophic cardiomyopathy (HCM) as performed in the clinical routine. Retrospectively identified, clinically diagnosed HCM patients with interventricular-septal (IVS) pattern hypertrophy who underwent CMR and echo within the same day were included. Left Ventricular WT was measured by CMR in two planes and compared to both echo and contrast echo (cecho). 72 subjects, mean age 50.7 ± 16.2 years, 68 % males. Interventricular septal WT by echo and CMR planes showed good to excellent correlation. However, measurements of the postero-lateral wall showed poor correlation. Bland-Altman plots showed greater maximal IVS WT by echo compared to CMR measurement [SAX = 1.7 mm (-5.8, 9.3); LVOT = 1.1 mm (-5.6, 7.8)]. Differences were smaller between cecho and CMR [SAX = 0.8 mm (-9.2, 10.8); LVOT = -0.2 mm (-10.0, 9.6)]. Severity of WT by quartiles showed greater differences between echo and SAX CMR WT compared to cecho. Echocardiography typically measures greater WT than CMR, with the largest differences in moderate to severe hypertrophy. Contrast echocardiography more closely approximates CMR measurements of WT. These findings have potential clinical implications for risk stratification of subjects with HCM.

  6. An ultrasound speckle tracking (two-dimensional strain) analysis of myocardial deformation in professional soccer players compared with healthy subjects and hypertrophic cardiomyopathy.

    PubMed

    Richand, Viviane; Lafitte, Stéphane; Reant, Patricia; Serri, Karim; Lafitte, Marianne; Brette, Stephanie; Kerouani, Akem; Chalabi, Hakim; Dos Santos, Pierre; Douard, Herve; Roudaut, Raymond

    2007-07-01

    Deformation analysis using 2-dimensional strain echocardiography can detect early systolic function abnormalities in patients with left ventricular hypertrophy. This study was designed to characterize global and regional myocardial deformation using 2-dimensional strain in professional soccer players (PSPs) compared with control subjects and patients with hypertrophic cardiomyopathy (HC). Twenty nine PSPs, 26 patients with HC, and 17 controls were investigated at rest using transthoracic echocardiography with 2-dimensional strain analysis. Radial and transverse strains were significantly higher in PSPs compared with controls, whereas longitudinal strain was lower. Compared with patients with HC, athletes had higher values for transverse, radial, and circumferential strains. In pathologic hypertrophic segments, longitudinal strain was lower in patients with HC than in PSPs. In conclusion, 2-dimensional strain can identify specific patterns of myocardial deformation in PSPs, controls, and patients with HC. It has the potential to become a routinely used method for the differentiation of athlete's heart and HC.

  7. Use of serum creatine kinase MM isoforms for predicting the progression of left ventricular dilation in patients with hypertrophic cardiomyopathy.

    PubMed

    Hina, K; Kusachi, S; Iwasaki, K; Takaishi, A; Yamamoto, K; Tominaga, Y; Kita, T; Tsuji, T

    1997-04-01

    Serum creatine kinase (CK) isoforms were examined to detect the progression of left ventricular (LV) enlargement with reduced motion, resembling dilated cardiomyopathy (DCM), in hypertrophic cardiomyopathy (HCM). Changes in LV indices were determined annually by echocardiography in 51 patients until serum measurements (first follow-up period, 6.5 +/- 2.2 years). Serum creatine isoforms (CKMM1, CKMM2 and CKMM3) were measured with high-voltage electrophoresis in 35 of these patients from 1991 to 1992, and the data for these latter patients are reported here. Serum total CK, CKMB, lactate dehydrogenase and its isoenzyme LDH1 were also measured. The changes in LV indices were further monitored until January, 1995 (second follow-up). During the 2 follow-up periods, the patients in the on-going group showed a reduction in the LV ejection fraction (LVEF) to < 55% with LV end-diastolic dimension (LVDd) < 55 mm, and those in the DCM-like group showed a reduction in LVEF to < 55% and an increase in LVDd to > 55 mm. During the first follow-up period, LVEF and LVDd remained at > or = 55% and < 55 mm, respectively, in 26 patients (nonprogressive-disease group), while 3 patients entered the on-going group and 6 entered the DCM-like group. The CKMM3/CKMM1 ratios in the on-going and DCM-like groups were significantly higher than those in the control and nonprogressive-disease groups. The CKMM3/CKMM1 ratio was significantly correlated with the annual rate of change for the LV end-systolic dimension (LVDs), LVDd, and LVEF, with the closest correlation observed for the annual change in LVDs. Moreover, 5 patients in the nonprogressive-disease group with elevation of the CKMM3/CKMM1 ratio to > + 2SD above the mean for the controls had an elevated annual change in LVDs within +/- 1SD of the mean in the DCM-like group. These results indicate that the ratio of CKMM3 to CKMM1 can be used to predict the progression of LV enlargement in HCM.

  8. Alcohol septal ablation for hypertrophic obstructive cardiomyopathy in a patient with a chronic total occlusion of the right coronary artery: “beware of collateral damage”

    PubMed Central

    de Hemptinne, Quentin; Picard, Fabien

    2017-01-01

    Alcohol septal ablation (ASA) is an effective semi-invasive alternative to surgical myectomy in selected patients for the management of severely symptomatic and drug-refractory hypertrophic obstructive cardiomyopathy (HOCM). One contraindication of this procedure is the presence of collateral flow originating from the target septal perforator to a remote myocardial territory. In such circumstances, ethanol injection could cause remote non-target myocardial necrosis in the collateralized territory. Percutaneous revascularization of the collateralized vessel prior to ASA might cope with this contraindication by restoring normal antegrade flow in the occluded artery. We report a case that illustrates the feasibility and efficacy of such strategy. PMID:28164017

  9. Myocardial perfusion abnormality in the area of ventricular septum-free wall junction and cardiovascular events in nonobstructive hypertrophic cardiomyopathy.

    PubMed

    Kaimoto, Satoshi; Kawasaki, Tatsuya; Kuribayashi, Toshiro; Yamano, Michiyo; Miki, Shigeyuki; Kamitani, Tadaaki; Matsubara, Hiroaki

    2012-10-01

    Myocardial perfusion abnormality in the left ventricle is known to be prognostic in patients with hypertrophic cardiomyopathy (HCM). Magnetic resonance imaging and necropsy studies on HCM hearts revealed myocardial lesions predominating in the area of ventricular septum-free wall junction. We assessed perfusion abnormality in this area and correlated it with the prognosis of HCM patients. We performed exercise Tc-99m tetrofosmin myocardial scintigraphy in 55 patients with nonobstructive HCM. Perfusion abnormalities were semiquantified using a 5-point scoring system in small areas of anterior junctions of basal, mid, and apical short axis views in addition to a conventional 17-segment model. All patients were prospectively followed for sudden death, cardiovascular death and hospitalization for heart failure or stroke associated with atrial fibrillation. Cardiovascular events occurred in 10 patients during an average follow-up period of 5.7 years. Stress and rest scores from anterior junction, and conventional summed stress score were significantly higher in patients with cardiovascular events than without (all P < 0.05). Anterior junction stress score of >2 produced a sensitivity of 50% and a specificity of 98% for cardiovascular events and was an independent predictor (hazard ratio 8.33; 95% confidence interval, 1.61-43.5; P = 0.01), with rest scores producing similar values, which were higher than summed stress score of >8 (5.68; 1.23-26.3; P = 0.03). The absence of myocardial perfusion abnormality in the narrow area of anterior junction differentiated HCM patients with low-risk.

  10. Tissue Doppler imaging and gradient echo cardiac magnetic resonance imaging in normal cats and cats with hypertrophic cardiomyopathy.

    PubMed

    MacDonald, Kristin A; Kittleson, Mark D; Garcia-Nolen, Tanya; Larson, Richard F; Wisner, Erik R

    2006-01-01

    Cats with hypertrophic cardiomyopathy (HCM) often develop diastolic dysfunction, which can lead to development of left congestive heart failure. Tissue Doppler imaging (TDI) echocardiography has emerged as a useful, noninvasive method for assessing diastolic function in cats. Cardiac magnetic resonance imaging (cMRI) has been performed in cats and accurately quantifies left ventricular (LV) mass in normal cats. However, assessment of cardiac function in cats by cMRI has not been performed. Six normal Domestic Shorthair cats and 7 Maine Coon cats with moderate to severe HCM were sedated, and TDI of the lateral mitral annulus was performed. Peak early diastolic velocity (Em) was measured from 5 nonconsecutive beats. Cats were anesthetized with propofol and electrocardiogram-gated gradient echo cMRI was performed during apnea after hyperventilation. Short-axis images of the LV extending from the mitral annulus to the apex were obtained throughout the cardiac cycle. LV mass at end systole and LV volumes throughout the cardiac cycle were quantified according to Simpson's rule. To assess the possible influence of propofol on diastolic function, TDI was performed on the 7 cats with HCM while sedated and then while anesthetized with propofol. Em was significantly lower in cats with HCM than normal cats (6.7 +/- 1.3 cm/s versus 11.6 +/- 1.9 cm/s, P < .001, respectively). There was no difference in the cMRI indices of diastolic function in normal and HCM cats. Propofol did not reduce diastolic function (Em) in cats with HCM but mildly reduced systolic myocardial velocity (S) in Maine Coon cats with HCM that were anesthetized with propofol (P = .87 and P = .03, respectively).

  11. Tissue Doppler imaging and plasma N-terminal probrain natriuretic peptide for the identification of hypertrophic cardiomyopathy mutation carriers.

    PubMed

    Silva, Doroteia; Madeira, Hugo; Almeida, Augusto; Brito, Dulce

    2013-10-01

    Previous studies have shown that tissue Doppler imaging (TDI) is able to identify mutation carriers of hypertrophic cardiomyopathy (HC) before the development of the clinical phenotype. However, data are scarce and have sometimes been controversial. We performed a systematic study that included conventional echocardiography, TDI, and plasma NT-probrain natriuretic peptide (NT-proBNP) measurement to evaluate the parameters that could identify HC mutation carriers. A total of 138 genotyped subjects were included and divided into 3 groups: group 1, those with HC (n = 62); group 2, mutation carriers (first-degree relatives with a positive genotype but negative phenotype; n = 34); and group 3, controls (first-degree relatives with a negative genotype and phenotype; n = 42). An echocardiographic study, including TDI, was performed on all subjects, and a TDI-derived index (global function index) was also determined. The age-adjusted mean differences in the echocardiographic and TDI parameters and NT-proBNP levels were compared among the 3 groups. Compared with the HC group, the carriers had significantly higher mean E' velocities, lower mean E/E' ratio, higher mean S' velocities, and lower mean global function index and NT-proBNP values. The carriers and controls did not differ significantly either in the echocardiographic parameters studied or in the NT-proBNP levels. In conclusion, the echocardiographic and TDI parameters and NT-proBNP levels cannot be used to identify the HC mutation carrier state and therefore do not appear to be reliable for the purpose of making a preclinical diagnosis of the disease.

  12. The structural and functional effects of the familial hypertrophic cardiomyopathy-linked cardiac troponin C mutation, L29Q.

    PubMed

    Robertson, Ian M; Sevrieva, Ivanka; Li, Monica X; Irving, Malcolm; Sun, Yin-Biao; Sykes, Brian D

    2015-10-01

    Familial hypertrophic cardiomyopathy (FHC) is characterized by severe abnormal cardiac muscle growth. The traditional view of disease progression in FHC is that an increase in the Ca(2+)-sensitivity of cardiac muscle contraction ultimately leads to pathogenic myocardial remodeling, though recent studies suggest this may be an oversimplification. For example, FHC may be developed through altered signaling that prevents downstream regulation of contraction. The mutation L29Q, found in the Ca(2+)-binding regulatory protein in heart muscle, cardiac troponin C (cTnC), has been linked to cardiac hypertrophy. However, reports on the functional effects of this mutation are conflicting, and our goal was to combine in vitro and in situ structural and functional data to elucidate its mechanism of action. We used nuclear magnetic resonance and circular dichroism to solve the structure and characterize the backbone dynamics and stability of the regulatory domain of cTnC with the L29Q mutation. The overall structure and dynamics of cTnC were unperturbed, although a slight rearrangement of site 1, an increase in backbone flexibility, and a small decrease in protein stability were observed. The structure and function of cTnC was also assessed in demembranated ventricular trabeculae using fluorescence for in situ structure. L29Q reduced the cooperativity of the Ca(2+)-dependent structural change in cTnC in trabeculae under basal conditions and abolished the effect of force-generating myosin cross-bridges on this structural change. These effects could contribute to the pathogenesis of this mutation.

  13. Registration of dynamic multiview 2D ultrasound and late gadolinium enhanced images of the heart: Application to hypertrophic cardiomyopathy characterization.

    PubMed

    Betancur, Julián; Simon, Antoine; Halbert, Edgar; Tavard, François; Carré, François; Hernández, Alfredo; Donal, Erwan; Schnell, Frédéric; Garreau, Mireille

    2016-02-01

    Describing and analyzing heart multiphysics requires the acquisition and fusion of multisensor cardiac images. Multisensor image fusion enables a combined analysis of these heterogeneous modalities. We propose to register intra-patient multiview 2D+t ultrasound (US) images with multiview late gadolinium-enhanced (LGE) images acquired during cardiac magnetic resonance imaging (MRI), in order to fuse mechanical and tissue state information. The proposed procedure registers both US and LGE to cine MRI. The correction of slice misalignment and the rigid registration of multiview LGE and cine MRI are studied, to select the most appropriate similarity measure. It showed that mutual information performs the best for LGE slice misalignment correction and for LGE and cine registration. Concerning US registration, dynamic endocardial contours resulting from speckle tracking echocardiography were exploited in a geometry-based dynamic registration. We propose the use of an adapted dynamic time warping procedure to synchronize cardiac dynamics in multiview US and cine MRI. The registration of US and LGE MRI was evaluated on a dataset of patients with hypertrophic cardiomyopathy. A visual assessment of 330 left ventricular regions from US images of 28 patients resulted in 92.7% of regions successfully aligned with cardiac structures in LGE. Successfully-aligned regions were then used to evaluate the abilities of strain indicators to predict the presence of fibrosis. Longitudinal peak-strain and peak-delay of aligned left ventricular regions were computed from corresponding regional strain curves from US. The Mann-Withney test proved that the expected values of these indicators change between the populations of regions with and without fibrosis (p < 0.01). ROC curves otherwise proved that the presence of fibrosis is one factor amongst others which modifies longitudinal peak-strain and peak-delay.

  14. Association of Noninvasively Measured Left Ventricular Mechanics With In Vitro Muscle Contractile Performance: A Prospective Study in Hypertrophic Cardiomyopathy Patients

    PubMed Central

    Dhillon, Ashwat; Sweet, Wendy; Popovic, Zoran B.; Smedira, Nicholas G.; Thamilarasan, Maran; Lytle, Bruce W.; Tan, Carmela; Starling, Randall C.; Lever, Harry M.; Moravec, Christine S.; Desai, Milind Y.

    2014-01-01

    Background Hypertrophic cardiomyopathy (HCM) is a primary myopathic process in which regional left ventricular dysfunction may exist without overt global left ventricular dysfunction. In obstructive HCM patients who underwent surgical myectomy (SM), we sought to determine if there is a significant association between echocardiographic longitudinal strain, histopathology, and in vitro myocardial performance (resting tension and developed tension) of the surgical specimen. Methods and Results HCM patients (n=122, 54±14 years, 54% men) undergoing SM were prospectively recruited. Longitudinal systolic strain and diastolic strain rates were measured at that basal septum (partially removed at SM) by using velocity vector imaging on preoperative echocardiography. Semiquantitative histopathologic grading of myocyte disarray and fibrosis and in vitro measurements of resting tension and developed tension were made in septal tissue obtained at SM. Mean basal septal systolic strain and diastolic strain rate were −8.3±5% and 0.62±0.4/s, while mild or greater degree of myocyte disarray and interstitial fibrosis were present in 85% and 87%, respectively. Mean resting tension and developed tension were 2.8±1 and 1.4±0.8 g/mm2. On regression analysis, basal septal systolic strain, diastolic strain rate, disarray, and fibrosis were associated with developed tension (β=0.19, 0.20, −0.33, and −0.40, respectively, all P<0.01) and resting tension (β=0.21, 0.22, −0.25, and −0.28, respectively, all P<0.01). Conclusion In obstructive HCM patients who underwent SM, left ventricular mechanics (echocardiographic longitudinal systolic strain and diastolic strain rates), assessed at the basal septum (myocardium removed during myectomy) and histopathologic findings characteristic for HCM (disarray and fibrosis) were significantly associated with in vitro myocardial resting and developed contractile performance. PMID:25389286

  15. A Small Molecule Inhibitor of Sarcomere Contractility Acutely Relieves Left Ventricular Outflow Tract Obstruction in Feline Hypertrophic Cardiomyopathy

    PubMed Central

    Stern, Joshua A.; Markova, Svetlana; Ueda, Yu; Kim, Jae B.; Pascoe, Peter J.; Evanchik, Marc J.; Green, Eric M.; Harris, Samantha P.

    2016-01-01

    Hypertrophic cardiomyopathy (HCM) is an inherited disease of the heart muscle characterized by otherwise unexplained thickening of the left ventricle. Left ventricular outflow tract (LVOT) obstruction is present in approximately two-thirds of patients and substantially increases the risk of disease complications. Invasive treatment with septal myectomy or alcohol septal ablation can improve symptoms and functional status, but currently available drugs for reducing obstruction have pleiotropic effects and variable therapeutic responses. New medical treatments with more targeted pharmacology are needed, but the lack of preclinical animal models for HCM with LVOT obstruction has limited their development. HCM is a common cause of heart failure in cats, and a subset exhibit systolic anterior motion of the mitral valve leading to LVOT obstruction. MYK-461 is a recently-described, mechanistically novel small molecule that acts at the sarcomere to specifically inhibit contractility that has been proposed as a treatment for HCM. Here, we use MYK-461 to test whether direct reduction in contractility is sufficient to relieve LVOT obstruction in feline HCM. We evaluated mixed-breed cats in a research colony derived from a Maine Coon/mixed-breed founder with naturally-occurring HCM. By echocardiography, we identified five cats that developed systolic anterior motion of the mitral valve and LVOT obstruction both at rest and under anesthesia when provoked with an adrenergic agonist. An IV MYK-461 infusion and echocardiography protocol was developed to serially assess contractility and LVOT gradient at multiple MYK-461 concentrations. Treatment with MYK-461 reduced contractility, eliminated systolic anterior motion of the mitral valve and relieved LVOT pressure gradients in an exposure-dependent manner. Our findings provide proof of principle that acute reduction in contractility with MYK-461 is sufficient to relieve LVOT obstruction. Further, these studies suggest that feline

  16. A Small Molecule Inhibitor of Sarcomere Contractility Acutely Relieves Left Ventricular Outflow Tract Obstruction in Feline Hypertrophic Cardiomyopathy.

    PubMed

    Stern, Joshua A; Markova, Svetlana; Ueda, Yu; Kim, Jae B; Pascoe, Peter J; Evanchik, Marc J; Green, Eric M; Harris, Samantha P

    2016-01-01

    Hypertrophic cardiomyopathy (HCM) is an inherited disease of the heart muscle characterized by otherwise unexplained thickening of the left ventricle. Left ventricular outflow tract (LVOT) obstruction is present in approximately two-thirds of patients and substantially increases the risk of disease complications. Invasive treatment with septal myectomy or alcohol septal ablation can improve symptoms and functional status, but currently available drugs for reducing obstruction have pleiotropic effects and variable therapeutic responses. New medical treatments with more targeted pharmacology are needed, but the lack of preclinical animal models for HCM with LVOT obstruction has limited their development. HCM is a common cause of heart failure in cats, and a subset exhibit systolic anterior motion of the mitral valve leading to LVOT obstruction. MYK-461 is a recently-described, mechanistically novel small molecule that acts at the sarcomere to specifically inhibit contractility that has been proposed as a treatment for HCM. Here, we use MYK-461 to test whether direct reduction in contractility is sufficient to relieve LVOT obstruction in feline HCM. We evaluated mixed-breed cats in a research colony derived from a Maine Coon/mixed-breed founder with naturally-occurring HCM. By echocardiography, we identified five cats that developed systolic anterior motion of the mitral valve and LVOT obstruction both at rest and under anesthesia when provoked with an adrenergic agonist. An IV MYK-461 infusion and echocardiography protocol was developed to serially assess contractility and LVOT gradient at multiple MYK-461 concentrations. Treatment with MYK-461 reduced contractility, eliminated systolic anterior motion of the mitral valve and relieved LVOT pressure gradients in an exposure-dependent manner. Our findings provide proof of principle that acute reduction in contractility with MYK-461 is sufficient to relieve LVOT obstruction. Further, these studies suggest that feline

  17. CCN2 plays a key role in extracellular matrix gene expression in severe hypertrophic cardiomyopathy and heart failure.

    PubMed

    Tsoutsman, Tatiana; Wang, Xiaoyu; Garchow, Kendra; Riser, Bruce; Twigg, Stephen; Semsarian, Christopher

    2013-09-01

    Hypertrophic cardiomyopathy (HCM) is the most common inherited primary myocardial disorder. HCM is characterized by interstitial fibrosis and excessive accumulation of extracellular matrix (ECM) proteins. Fibrosis in HCM has been associated with impaired cardiac function and heart failure, and has been considered a key substrate for ventricular arrhythmias and sudden death. The molecular triggers underpinning ECM production are not well established. We have previously developed a double-mutant mouse model of HCM that recapitulates the phenotype seen in humans with multiple mutations, including earlier onset of the disease, progression to a dilated phenotype, severe heart failure and premature mortality. The present study investigated the expression of ECM-encoding genes in severe HCM and heart failure. Significant upregulation of structural Fn1, regulatory Mmp14, Timp1, Serpin3A, SerpinE1, SerpineE2, Tgfβ1, and Tgfβ2; and matricellular Ccn2, Postn, Spp1, Thbs1, Thbs4, and Tnc was evident from the early, pre-phenotype stage. Non-myocytes expressed ECM genes at higher levels than cardiomyocytes in normal and diseased hearts. Synchronous increase of secreted CCN2 and TIMP1 plasma levels and decrease of MMP3 levels were observed in end-stage disease. CCN2 protein expression was increased from early disease in double-mutant hearts and played an important role in ECM responses. It was a powerful modulator of ECM regulatory (Timp1 and SerpinE1) and matricellular protein-encoding (Spp1, Thbs1, Thbs4 and Tnc) gene expression in cardiomyocytes when added exogenously in vitro. Modulation of CCN2 (CTGF, connective tissue growth factor) and associated early ECM changes may represent a new therapeutic target in the treatment and prevention of heart failure in HCM.

  18. Outcome of patients with hypertrophic obstructive cardiomyopathy after percutaneous transluminal septal myocardial ablation and septal myectomy surgery

    NASA Technical Reports Server (NTRS)

    Qin, J. X.; Shiota, T.; Lever, H. M.; Kapadia, S. R.; Sitges, M.; Rubin, D. N.; Bauer, F.; Greenberg, N. L.; Agler, D. A.; Drinko, J. K.; Martin, M.; Tuzcu, E. M.; Smedira, N. G.; Lytle, B.; Thomas, J. D.

    2001-01-01

    OBJECTIVES: This study was conducted to evaluate follow-up results in patients with hypertrophic obstructive cardiomyopathy (HOCM) who underwent either percutaneous transluminal septal myocardial ablation (PTSMA) or septal myectomy. BACKGROUND: Controversy exists with regard to these two forms of treatment for patients with HOCM. METHODS: Of 51 patients with HOCM treated, 25 were treated by PTSMA and 26 patients via myectomy. Two-dimensional echocardiograms were performed before both procedures, immediately afterwards and at a three-month follow-up. The New York Heart Association (NYHA) functional class was obtained before the procedures and at follow-up. RESULTS: Interventricular septal thickness was significantly reduced at follow-up in both groups (2.3 +/- 0.4 cm vs. 1.9 +/- 0.4 cm for septal ablation and 2.4 +/- 0.6 cm vs. 1.7 +/- 0.2 cm for myectomy, both p < 0.001). Estimated by continuous-wave Doppler, the resting pressure gradient (PG) across the left ventricular outflow tract (LVOT) significantly decreased immediately after the procedures in both groups (64 +/- 39 mm Hg vs. 28 +/- 29 mm Hg for PTSMA, 62 +/- 43 mm Hg vs. 7 +/- 7 mm Hg for myectomy, both p < 0.0001). At three-month follow-up, the resting PG remained lower in the PTSMA and myectomy groups (24 +/- 19 mm Hg and 11 +/- 6 mm Hg, respectively, vs. those before procedures, both p < 0.0001). The NYHA functional class was also significantly improved in both groups (3.5 +/- 0.5 vs. 1.9 +/- 0.7 for PTSMA, 3.3 +/- 0.5 vs. 1.5 +/- 0.7 for myectomy, both p < 0.0001). CONCLUSIONS: Both myectomy and PTSMA reduce LVOT obstruction and significantly improve NYHA functional class in patients with HOCM. However, there are benefits and drawbacks for each therapeutic method that must be counterbalanced when deciding on treatment for LVOT obstruction.

  19. Myocardial triglyceride content in patients with left ventricular hypertrophy: comparison between hypertensive heart disease and hypertrophic cardiomyopathy.

    PubMed

    Sai, Eiryu; Shimada, Kazunori; Yokoyama, Takayuki; Hiki, Makoto; Sato, Shuji; Hamasaki, Nozomi; Maruyama, Masaki; Morimoto, Ryoko; Miyazaki, Tetsuro; Fujimoto, Shinichiro; Tamura, Yoshifumi; Aoki, Shigeki; Watada, Hirotaka; Kawamori, Ryuzo; Daida, Hiroyuki

    2017-02-01

    Proton magnetic resonance spectroscopy ((1)H-MRS) enables the assessment of myocardial triglyceride (TG) content, which is reported to be associated with cardiac dysfunction and morphology accompanied by metabolic disorder and cardiac hemodynamic status. The clinical usefulness of myocardial TG content measurements in patients with left ventricular hypertrophy (LVH) has not been fully investigated. We examined whether myocardial TG content assessed by (1)H-MRS was useful for diagnosis in patients with LVH. To quantify myocardial TG content, we conducted (1)H-MRS in 35 subjects with LVH. Left ventricular function was measured by cardiac magnetic resonance imaging. Patients were assigned to a hypertensive heart disease (HHD, n = 10) or hypertrophic cardiomyopathy (HCM, n = 25) group based on the histology and/or late gadolinium enhancement pattern. The myocardial TG content was significantly higher in the HHD group than in the HCM group (2.14 ± 1.29 vs. 1.09 ± 0.72 %, P < 0.001). Myocardial TG content were significantly and negatively correlated with LV mass (r = -0.41, P < 0.04) and stroke volume (r = -0.64, P < 0.05) in the HCM group and HHD group, respectively. In a multivariate analysis, LV mass volume and diagnosis of HCM or HHD were independent factors of the myocardial TG content. The results suggest that myocardial metabolism may differ between HCM and HHD patients and that measurement of myocardial TG content by (1)H-MRS may be useful for evaluating the myocardial metabolic features of LVH.

  20. The prognostic value of standardized reference values for speckle-tracking global longitudinal strain in hypertrophic cardiomyopathy.

    PubMed

    Hartlage, Gregory R; Kim, Jonathan H; Strickland, Patrick T; Cheng, Alan C; Ghasemzadeh, Nima; Pernetz, Maria A; Clements, Stephen D; Williams, B Robinson

    2015-03-01

    Speckle-tracking left ventricular global longitudinal strain (GLS) assessment may provide substantial prognostic information for hypertrophic cardiomyopathy (HCM) patients. Reference values for GLS have been recently published. We aimed to evaluate the prognostic value of standardized reference values for GLS in HCM patients. An analysis of HCM clinic patients who underwent GLS was performed. GLS was defined as normal (more negative or equal to -16%) and abnormal (less negative than -16%) based on recently published reference values. Patients were followed for a composite of events including heart failure hospitalization, sustained ventricular arrhythmia, and all-cause death. The power of GLS to predict outcomes was assessed relative to traditional clinical and echocardiographic variables present in HCM. 79 HCM patients were followed for a median of 22 months (interquartile range 9-30 months) after imaging. During follow-up, 15 patients (19%) met the primary outcome. Abnormal GLS was the only echocardiographic variable independently predictive of the primary outcome [multivariate Hazard ratio 5.05 (95% confidence interval 1.09-23.4, p = 0.038)]. When combined with traditional clinical variables, abnormal GLS remained independently predictive of the primary outcome [multivariate Hazard ratio 5.31 (95 % confidence interval 1.18-24, p = 0.030)]. In a model including the strongest clinical and echocardiographic predictors of the primary outcome, abnormal GLS demonstrated significant incremental benefit for risk stratification [net reclassification improvement 0.75 (95 % confidence interval 0.21-1.23, p < 0.0001)]. Abnormal GLS is an independent predictor of adverse outcomes in HCM patients. Standardized use of GLS may provide significant incremental value over traditional variables for risk stratification.

  1. Cardiac-Specific Over-Expression of Epidermal Growth Factor Receptor 2 (ErbB2) Induces Pro-Survival Pathways and Hypertrophic Cardiomyopathy in Mice

    PubMed Central

    Guo, Xin; Belmonte, Frances; Kang, Byunghak; Bedja, Djahida; Pin, Scott; Tsuchiya, Noriko; Gabrielson, Kathleen

    2012-01-01

    Background Emerging evidence shows that ErbB2 signaling has a critical role in cardiomyocyte physiology, based mainly on findings that blocking ErbB2 for cancer therapy is toxic to cardiac cells. However, consequences of high levels of ErbB2 activity in the heart have not been previously explored. Methodology/Principal Findings We investigated consequences of cardiac-restricted over-expression of ErbB2 in two novel lines of transgenic mice. Both lines develop striking concentric cardiac hypertrophy, without heart failure or decreased life span. ErbB2 transgenic mice display electrocardiographic characteristics similar to those found in patients with Hypertrophic Cardiomyopathy, with susceptibility to adrenergic-induced arrhythmias. The hypertrophic hearts, which are 2–3 times larger than those of control littermates, express increased atrial natriuretic peptide and β-myosin heavy chain mRNA, consistent with a hypertrophic phenotype. Cardiomyocytes in these hearts are significantly larger than wild type cardiomyocytes, with enlarged nuclei and distinctive myocardial disarray. Interestingly, the over-expression of ErbB2 induces a concurrent up-regulation of multiple proteins associated with this signaling pathway, including EGFR, ErbB3, ErbB4, PI3K subunits p110 and p85, bcl-2 and multiple protective heat shock proteins. Additionally, ErbB2 up-regulation leads to an anti-apoptotic shift in the ratio of bcl-xS/xL in the heart. Finally, ErbB2 over-expression results in increased activation of the translation machinery involving S6, 4E-BP1 and eIF4E. The dependence of this hypertrophic phenotype on ErbB family signaling is confirmed by reduction in heart mass and cardiomyocyte size, and inactivation of pro-hypertrophic signaling in transgenic animals treated with the ErbB1/2 inhibitor, lapatinib. Conclusions/Significance These studies are the first to demonstrate that increased ErbB2 over-expression in the heart can activate protective signaling pathways and induce a

  2. Obstructive Form of Hypertrophic Cardiomyopathy-Left Ventricular Outflow Tract Gradient: Novel Methods of Provocation, Monitoring of Biomarkers, and Recent Advances in the Treatment

    PubMed Central

    Dimitrow, Pawel Petkow; Rajtar-Salwa, Renata

    2016-01-01

    Dynamic (latent or/and labile) obstruction of left ventricular outflow (LVOT) was recognized from the earliest clinical descriptions of hypertrophic cardiomyopathy (HCM) and has proved to be a complex phenomenon, as well as arguably the most audible (“visible”) pathophysiological hallmark of this heterogeneous disease. The aim of the current review is focused on two novel issues in a subgroup of obstructive HCM. Firstly, the important methodological problem in HCM is the examination of a subgroup of patients with nonobstructive hypertrophy in resting conditions and hard, but possible provoking obstruction. Recently, investigators have proposed physiological stress test (with double combined stimuli) to disclose such type of patients. The upright exercise is described in the ESC guideline on hypertrophic cardiomyopathy from 2014 and may appear as a candidate for gold standard provocation test. The second novel area of interest is associated with elevated level of signaling biomarkers: hypercoagulation, hemolysis, acquired von Willebrand 2A disease, and enhanced oxidative stress. The accelerated and turbulent flow within narrow LVOT may be responsible for these biochemical disturbances. The most recent advances in the treatment of obstructive HCM are related to nonpharmacological methods of LVOT gradient reduction. This report extensively discusses novel methods. PMID:27247935

  3. Decreased interactions of mutant muscle LIM protein (MLP) with N-RAP and alpha-actinin and their implication for hypertrophic cardiomyopathy.

    PubMed

    Gehmlich, Katja; Geier, Christian; Osterziel, Karl Josef; Van der Ven, Peter F M; Fürst, Dieter O

    2004-08-01

    Previous work has shown that mutations in muscle LIM protein (MLP) can cause hypertrophic cardiomyopathy (HCM). In order to gain an insight into the molecular basis of the disease phenotype, we analysed the binding characteristics of wild-type MLP and of the (C58G) mutant MLP that causes hypertrophic cardiomyopathy. We show that MLP can form a ternary complex with two of its previously documented myofibrillar ligand proteins, N-RAP and alpha-actinin, which indicates the presence of distinct, non-overlapping binding sites. Our data also show that, in comparison to wild-type MLP, the capacity of the mutated MLP protein to bind both N-RAP and alpha-actinin is significantly decreased. In addition, this single point mutation prevents zinc coordination and proper folding of the second zinc-finger in the first LIM domain, which consequently renders the protein less stable and more susceptible to proteolysis. The molecular basis for HCM-causing mutations in the MLP gene might therefore be an alteration in the equilibrium of interactions of the ternary complex MLP-N-RAP-alpha-actinin. This assumption is supported by the previous observation that in the pathological situation accompanied by MLP down regulation, cardiomyocytes try to compensate for the decreased stability of MLP protein by increasing the expression of its ligand N-RAP, which might finally result in the development of myocyte disarray that is characteristic of this disease.

  4. Subendocardial motion in hypertrophic cardiomyopathy: assessment from long- and short-axis views by pulsed tissue Doppler imaging

    NASA Technical Reports Server (NTRS)

    Tabata, T.; Oki, T.; Yamada, H.; Abe, M.; Onose, Y.; Thomas, J. D.

    2000-01-01

    BACKGROUND: Tissue Doppler imaging (TDI) is a recently developed technique that allows the instantaneous measurement of intrinsic regional myocardial motion velocity. Pulsed TDI is capable of separately assessing left ventricular (LV) regional motion velocity caused by circumferential and longitudinal fiber contraction. This particular feature of function is still controversial in patients with hypertrophic cardiomyopathy (HC). METHODS: To better characterize intrinsic circumferential and longitudinal LV systolic myocardial function in HC, we used pulsed TDI to measure short- and long-axis LV motion velocities, respectively. The subendocardial motion velocity patterns at the middle of the LV posterior wall (PW) and ventricular septum (IVS) in LV parasternal and apical long-axis views were recorded by pulsed TDI in 19 patients with nonobstructive HC and in 21 normal controls (NC). RESULTS: Peak short- and long-axis systolic subendocardial velocities in both the LV PW and IVS were significantly smaller in the HC group than in the NC group, and the time to peak velocity was significantly delayed. Furthermore, peak PW systolic velocity was significantly greater along the long axis than along the short axis in the NC group (8.8 +/- 1.5 cm/s vs 8.2 +/- 1.4 cm/s, P <.05), whereas the opposite was observed in the HC group (6.1 +/- 1.2 cm/s vs 7.5 +/- 1.0 cm/s, P <.0001). No significant differences were found in either group between the long- and short-axis IVS velocities (HC: 5.9 +/- 1.4 cm/s vs 5.5 +/- 1.3 cm/s; NC: 7.8 +/- 1.3 cm/s vs 7.9 +/- 1.6 cm/s). CONCLUSIONS: By using the capability of pulsed TDI for the evaluation of intrinsic myocardial velocity instantaneously in a specific region and direction, we found impairment of LV myocardial systolic function in patients with HC not only in the hypertrophied IVS but also in the nonhypertrophied LV PW. We also found a greater decrease in LV PW velocities along the long axis than the short axis, suggesting greater

  5. Tissue Doppler Imaging Combined with Advanced 12-Lead ECG Analysis Might Improve Early Diagnosis of Hypertrophic Cardiomyopathy in Childhood

    NASA Technical Reports Server (NTRS)

    Femlund, E.; Schlegel, T.; Liuba, P.

    2011-01-01

    Optimization of early diagnosis of childhood hypertrophic cardiomyopathy (HCM) is essential in lowering the risk of HCM complications. Standard echocardiography (ECHO) has shown to be less sensitive in this regard. In this study, we sought to assess whether spatial QRS-T angle deviation, which has shown to predict HCM in adults with high sensitivity, and myocardial Tissue Doppler Imaging (TDI) could be additional tools in early diagnosis of HCM in childhood. Methods: Children and adolescents with familial HCM (n=10, median age 16, range 5-27 years), and without obvious hypertrophy but with heredity for HCM (n=12, median age 16, range 4-25 years, HCM or sudden death with autopsy-verified HCM in greater than or equal to 1 first-degree relative, HCM-risk) were additionally investigated with TDI and advanced 12-lead ECG analysis using Cardiax(Registered trademark) (IMED Co Ltd, Budapest, Hungary and Houston). Spatial QRS-T angle (SA) was derived from Kors regression-related transformation. Healthy age-matched controls (n=21) were also studied. All participants underwent thorough clinical examination. Results: Spatial QRS-T angle (Figure/ Panel A) and septal E/Ea ratio (Figure/Panel B) were most increased in HCM group as compared to the HCM-risk and control groups (p less than 0.05). Of note, these 2 variables showed a trend toward higher levels in HCM-risk group than in control group (p=0.05 for E/Ea and 0.06 for QRS/T by ANOVA). In a logistic regression model, increased SA and septal E/Ea ratio appeared to significantly predict both the disease (Chi-square in HCM group: 9 and 5, respectively, p less than 0.05 for both) and the risk for HCM (Chi-square in HCM-risk group: 5 and 4 respectively, p less than 0.05 for both), with further increased predictability level when these 2 variables were combined (Chi-square 10 in HCM group, and 7 in HCM-risk group, p less than 0.01 for both). Conclusions: In this small material, Tissue Doppler Imaging and spatial mean QRS-T angle

  6. Assessment of intravascular and extravascular mechanisms of myocardial perfusion abnormalities in obstructive hypertrophic cardiomyopathy by myocardial contrast echocardiography

    PubMed Central

    Soliman, Osama I I; Knaapen, Paul; Geleijnse, Marcel L; Dijkmans, Pieter A; Anwar, Ashraf M; Nemes, Attila; Michels, Michelle; Vletter, Wim B; Lammertsma, Adriaan A

    2007-01-01

    Objectives To assess mechanisms of myocardial perfusion impairment in patients with hypertrophic cardiomyopathy (HCM). Methods Fourteen patients with obstructive HCM (mean (SD) age 53 (10) years, 11 men) underwent intravenous adenosine myocardial contrast echocardiography (MCE), positron emission tomography (PET) and cardiac catheterisation. Fourteen healthy volunteers (mean age 31 (4) years, 11 men) served as controls. Relative myocardial blood volume (rBV), exchange flow velocity (β), myocardial blood flow (MBF), MBF reserve (MFR) and endocardial‐to‐subepicardial (endo‐to‐epi) MBF ratio were measured from the steady state and contrast replenishment time–intensity curves. Results Patients with HCM had lower rest MBF (for LVRPP‐corrected)—mean (SD) (0.92 (0.12) vs 1.13 (0.25) ml/min/g, p<0.01)—and hyperaemic MBF—(2.56 (0.49) vs 4.34 (0.78) ml/min/g, p<0.01) than controls. Resting rBV was lower in patients with HCM (0.094 (0.016) vs 0.138 (0.014) ml/ml), and during hyperaemia (0.104 (0.018) ml/ml vs 0.185 (0.024) ml/ml) (all p<0.001) than in controls. β tended to be higher in HCM at rest (9.4 (4.6) vs 7.7 (4.2) ml/min) and during hyperaemia (25.8 (6.4) vs 23.1 (6.2) ml/min) than in controls. Septal endo‐to‐epi MBF decreased during hyperaemia (0.86 (0.15) to 0.64 (0.18), p<0.01). rBV was inversely correlated with left ventricular (LV) mass index (p<0.05). Both hyperaemic and endo‐to‐epi MBF were inversely correlated with LV end‐diastolic pressure, LV mass index, and LV outflow tract pressure gradient (all p<0.05). MCE‐derived MBF correlated well with PET at rest (r = 0.84) and hyperaemia (r = 0.87) (all p<0.001). Conclusions In patients with HCM, LV end‐diastolic pressure, LV outflow tract pressure gradient, and LV mass index are independent predictors of rBV and hyperaemic MBF. PMID:17488767

  7. Utility of T-wave amplitude as a non-invasive risk marker of sudden cardiac death in hypertrophic cardiomyopathy

    PubMed Central

    Sugrue, Alan; Killu, Ammar M; DeSimone, Christopher V; Chahal, Anwar A; Vogt, Josh C; Kremen, Vaclav; Hai, JoJo; Hodge, David O; Acker, Nancy G; Geske, Jeffrey B; Ackerman, Michael J; Ommen, Steve R; Lin, Grace; Noseworthy, Peter A; Brady, Peter A

    2017-01-01

    Objective Sudden cardiac arrest (SCA) is the most devastating outcome in hypertrophic cardiomyopathy (HCM). We evaluated repolarisation features on the surface electrocardiogram (ECG) to identify the potential risk factors for SCA. Methods Data was collected from 52 patients with HCM who underwent implantable cardioverter defibrillator (ICD) implantation. Leads V2 and V5 from the ECG closest to the time of ICD implant were utilised for measuring the Tpeak-Tend interval (Tpe), QTc, Tpe/QTc, T-wave duration and T-wave amplitude. The presence of the five traditional SCA-associated risk factors was assessed, as well as the HCM risk-SCD score. Results 16 (30%) patients experienced aborted cardiac arrest over 8.5±4.1 years, with 9 receiving an ICD shock and 7 receiving ATP. On univariate analysis, T-wave amplitude was associated with appropriate ICD therapy (HR per 0.1 mV 0.79, 95% CI 0.56 to 0.96, p=0.02). Aborted SCA was not associated with a greater mean QTc duration, Tpeak-Tend interval, T-wave duration, or Tpe/QT ratio. Multivariate analysis (adjusting for cardinal HCM SCA-risk factors) showed T-wave amplitude in Lead V2 was an independent predictor of risk (adjusted HR per 0.1 mV 0.74, 95% CI 0.57 to 0.97, p=0.03). Addition of T-wave amplitude in Lead V2 to the traditional risk factors resulted in significant improvement in risk stratification (C-statistic from 0.65 to 0.75) but did not improve the performance of the HCM SCD-risk score. Conclusions T-wave amplitude is a novel marker of SCA in this high risk HCM population and may provide incremental predictive value to established risk factors. Further work is needed to define the role of repolarisation abnormalities in predicting SCA in HCM.

  8. Predictors of heart-focused anxiety in patients undergoing genetic investigation and counseling of long QT syndrome or hypertrophic cardiomyopathy: a one year follow-up.

    PubMed

    Hamang, Anniken; Eide, Geir Egil; Rokne, Berit; Nordin, Karin; Bjorvatn, Cathrine; Øyen, Nina

    2012-02-01

    Since Long QT syndrome and Hypertrophic cardiomyopathy are inherited cardiac disorders that may cause syncope, palpitations, serious arrhythmias, and sudden cardiac death, at-risk individuals may experience heart-focused anxiety. In a prospective multi-site study, 126 Norwegian patients attending genetic counseling were followed 1 year with multiple administration of questionnaires, including the Cardiac Anxiety Questionnaire, measuring three distinct symptoms of heart-focused anxiety- avoidance, attention, and fear-in mixed linear analyses. Overall, at 1-year follow-up, patients with clinical diagnosis as compared to patients at genetic risk had significantly higher scores of avoidance (p < .002), attention (p < .005), and fear (p < .007). Sudden cardiac death in close relatives, uncertainty whether other relatives previously had undergone genetic testing, patients' perceived general health, self-efficacy expectations and procedural satisfaction with genetic counseling were influential in predicting the different symptoms of heart-focused anxiety over time.

  9. Early-Onset Hypertrophic Cardiomyopathy Mutations Significantly Increase the Velocity, Force, and Actin-Activated ATPase Activity of Human β-Cardiac Myosin.

    PubMed

    Adhikari, Arjun S; Kooiker, Kristina B; Sarkar, Saswata S; Liu, Chao; Bernstein, Daniel; Spudich, James A; Ruppel, Kathleen M

    2016-12-13

    Hypertrophic cardiomyopathy (HCM) is a heritable cardiovascular disorder that affects 1 in 500 people. A significant percentage of HCM is attributed to mutations in β-cardiac myosin, the motor protein that powers ventricular contraction. This study reports how two early-onset HCM mutations, D239N and H251N, affect the molecular biomechanics of human β-cardiac myosin. We observed significant increases (20%-90%) in actin gliding velocity, intrinsic force, and ATPase activity in comparison to wild-type myosin. Moreover, for H251N, we found significantly lower binding affinity between the S1 and S2 domains of myosin, suggesting that this mutation may further increase hyper-contractility by releasing active motors. Unlike previous HCM mutations studied at the molecular level using human β-cardiac myosin, early-onset HCM mutations lead to significantly larger changes in the fundamental biomechanical parameters and show clear hyper-contractility.

  10. Sporadic myopathy, myoclonus, leukoencephalopathy, neurosensory deafness, hypertrophic cardiomyopathy and insulin resistance associated with the mitochondrial 8306 T>C MTTK mutation.

    PubMed

    Cardaioli, Elena; Malfatti, Edoardo; Battisti, Carla; Da Pozzo, Paola; Rubegni, Anna; Gallus, Gian Nicola; Malandrini, Alessandro; Federico, Antonio

    2012-10-15

    We report a new T8306C transition in the D-stem of the MTTK gene of a 67-year-old man who manifested severe adult onset myopathy, myoclonus, leukoencephalopathy, neurosensory hypoacusis, hypertrophic cardiomyopathy and insulin resistance. No other family member was affected, suggesting that our patient was a sporadic case. The T8306C mutation was heteroplasmic in several tissues of the proband, while it was absent from his asymptomatic siblings. Single fibre analysis confirmed the segregation of higher mutational load in cytochrome c oxidase-deficient fibres. The mutation T8306C is predicted to disrupt a highly conserved base pair and was not found in more than 120 controls. This finding broadens the phenotypic and molecular spectrum of mitochondrial tRNA(Lys) associated disorders.

  11. Fast diastolic swinging motion of the mitral valve as a clinical marker of familial hypertrophic cardiomyopathy in genetically affected young children without left ventricular hypertrophy: a new role for noninvasive imaging?

    PubMed

    Udink ten Cate, Floris E A; Junghaenel, Shino; Brockmeier, Konrad; Sreeram, Narayanswami

    2013-08-01

    Structural mitral valve (MV) abnormalities are common in patients with hypertrophic cardiomyopathy (HCM). This is the first report demonstrating MV abnormalities in very young children as the sole overt clinical feature of a known HCM-causing sarcomere protein gene mutation. Due to MV leaflet elongation, we also noticed a typical fast diastolic swinging motion of the MV in our patients. This novel echocardiographic feature may be used as a clinical marker of HCM disease in the absence of left ventricular hypertrophy.

  12. Cardiomyopathy in neurological disorders.

    PubMed

    Finsterer, Josef; Stöllberger, Claudia; Wahbi, Karim

    2013-01-01

    According to the American Heart Association, cardiomyopathies are classified as primary (solely or predominantly confined to heart muscle), secondary (those showing pathological myocardial involvement as part of a neuromuscular disorder) and those in which cardiomyopathy is the first/predominant manifestation of a neuromuscular disorder. Cardiomyopathies may be further classified as hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, or unclassified cardiomyopathy (noncompaction, Takotsubo-cardiomyopathy). This review focuses on secondary cardiomyopathies and those in which cardiomyopathy is the predominant manifestation of a myopathy. Any of them may cause neurological disease, and any of them may be a manifestation of a neurological disorder. Neurological disease most frequently caused by cardiomyopathies is ischemic stroke, followed by transitory ischemic attack, syncope, or vertigo. Neurological disease, which most frequently manifests with cardiomyopathies are the neuromuscular disorders. Most commonly associated with cardiomyopathies are muscular dystrophies, myofibrillar myopathies, congenital myopathies and metabolic myopathies. Management of neurological disease caused by cardiomyopathies is not at variance from the same neurological disorders due to other causes. Management of secondary cardiomyopathies is not different from that of cardiomyopathies due to other causes either. Patients with neuromuscular disorders require early cardiologic investigations and close follow-ups, patients with cardiomyopathies require neurological investigation and avoidance of muscle toxic medication if a neuromuscular disorder is diagnosed. Which patients with cardiomyopathy profit most from primary stroke prevention is unsolved and requires further investigations.

  13. Ventricular hypertrophy in cardiomyopathy.

    PubMed

    Oakley, C

    1971-01-01

    Semantic difficulties arise when hypertrophic obstructive cardiomyopathy is seen without obstruction and with congestive failure, and also when congestive cardiomyopathy is seen with gross hypertrophy but without heart failure. Retention of a small left ventricular cavity and a normal ejection fraction characterizes hypertrophic cardiomyopathy at all stages of the disorder. Congestive cardiomyopathy is recognized by the presence of a dilated left ventricular cavity and reduced ejection fraction regardless of the amount of hypertrophy and the presence or not of heart failure. Longevity in congestive cardiomyopathy seems to be promoted when hypertrophy is great relative to the amount of pump failure as measured by increase in cavity size. Conversely, death in hypertrophic cardiomyopathy is most likely when hypertrophy is greatest at a time when outflow tract obstruction has been replaced by inflow restriction caused by diminishing ventricular distensibility. Hypertrophy is thus beneficial and compensatory in congestive cardiomyopathy, whereas it may be the primary disorder and eventual cause of death in hypertrophic cardiomyopathy. Reasons are given for believing that hypertension may have been the original cause of left ventricular dilatation in some case of congestive cardiomyopathy in which loss of stroke output thenceforward is followed by normotension. Development of severe hypertension in these patients after recovery from a prolonged period of left ventricular failure with normotension lends weight to this hypothesis. No fault has been found in the large or small coronary arteries in either hypertrophic cardiomyopathy or congestive cardiomyopathy when they have been examined in life by selective coronary angiography, or by histological methods in biopsy or post-mortem material. Coronary blood supply may be a limiting factor in the compensatory hypertrophy of congestive cardiomyopathy, and the ability to hypertrophy may explain the better prognosis of some

  14. Prognostic value of non-sustained ventricular tachycardia and the potential role of amiodarone treatment in hypertrophic cardiomyopathy: assessment in an unselected non-referral based patient population

    PubMed Central

    Cecchi, F; Olivotto, I; Montereggi, A; Squillatini, G; Dolara, A; Maron, B

    1998-01-01

    Background—Amiodarone has been reported to reduce the likelihood of sudden death in patients with hypertrophic cardiomyopathy (HCM). However, data regarding the clinical course in HCM have traditionally come from selected referral populations biased toward assessment of high risk patients.
Aims—To evaluate antiarrhythmic treatment for sudden death in an HCM population not subject to tertiary referral bias, closely resembling the true disease state present in the community.
Methods—Cardiovascular mortality was assessed in relation to the occurrence of non-sustained ventricular tachycardia (NSVT) on 24 or 48 hour ambulatory Holter recording, a finding previously regarded as a marker for sudden death, particularly when the arrhythmia was frequent, repetitive or prolonged. 167 consecutive patients were analysed by multiple Holter ECG recordings (mean (SD) 157 (129) hours) and followed for a mean of 10 (5) years. Only patients with multiple repetitive NSVT were treated with amiodarone, and in relatively low doses (220 (44) mg/day).
Results—Nine HCM related deaths occurred: 8 were the consequence of congestive heart failure, but only 1 was sudden and unexpected. Three groups of patients were segregated based on their NSVT profile: group 1 (n = 39), multiple (⩾ 2 runs) and repetitive bursts (on ⩾ 2 Holters) of NSVT, or prolonged runs of ventricular tachycardia, included 4 deaths due to heart failure; group 2 (n = 38), isolated infrequent bursts of NSVT, included 1 sudden death; group 3 (n = 90), without NSVT, included 4 heart failure deaths. Kaplan-Meier survival analysis showed no significant differences in survival between the three groups throughout follow up.
Conclusions—In an unselected patient population with HCM, isolated, non-repetitive bursts of NSVT were not associated with adverse prognosis and so this arrhythmia does not appear to justify chronic antiarrhythmic treatment. Amiodarone, administered in relatively low

  15. Comparison of left ventricular diastolic function in obstructive hypertrophic cardiomyopathy in patients undergoing percutaneous septal alcohol ablation versus surgical myotomy/myectomy

    NASA Technical Reports Server (NTRS)

    Sitges, Marta; Shiota, Takahiro; Lever, Harry M.; Qin, Jian Xin; Bauer, Fabrice; Drinko, Jeannie K.; Agler, Deborah A.; Martin, Maureen G.; Greenberg, Neil L.; Smedira, Nicholas G.; Lytle, Bruce W.; Tuzcu, E. Murat; Garcia, Mario J.; Thomas, James D.

    2003-01-01

    Both percutaneous transcoronary alcohol septal reduction (ASR) and surgical myectomy are effective treatments to relieve left ventricular (LV) outflow tract obstruction in obstructive hypertrophic cardiomyopathy (HC). LV diastolic function was assessed by echocardiography in 57 patients with obstructive HC at baseline and 5 +/- 4 months after ASR (n = 37) or surgical myectomy (n = 20). LV outflow tract pressure gradient decreased from 65 +/- 40 to 23 +/- 21 mm Hg (p <0.01) after treatment. The ratio of the early-to-late peak diastolic LV inflow velocities, and the ratio of the early peak diastolic LV inflow velocity to the lateral mitral annulus early diastolic velocity determined by tissue Doppler imaging significantly decreased after the procedures (1.6 +/- 1.7 vs 1.0 +/- 0.7 and 15 +/- 8 vs 11 +/- 5, respectively), whereas LV inflow propagation velocity significantly increased (60 +/- 24 vs 71 +/- 36 cm/s). Left atrial size decreased from 29 +/- 7 to 25 +/- 6 cm(2) (p <0.05). Patients had a significant improvement in New York Heart Association functional class and in exercise performance. When comparing ASR with myectomy, no difference was found in the degree of change in any parameter of diastolic function. Thus, diastolic function indexes obtained by echocardiography changed after septal reduction interventions in patients with obstructive HC; this change was similar to that after surgical myectomy and ASR.

  16. Quantification of local changes in myocardial motion by diffeomorphic registration via currents: application to paced hypertrophic obstructive cardiomyopathy in 2D echocardiographic sequences.

    PubMed

    Duchateau, Nicolas; Giraldeau, Geneviève; Gabrielli, Luigi; Fernández-Armenta, Juan; Penela, Diego; Evertz, Reinder; Mont, Lluis; Brugada, Josep; Berruezo, Antonio; Sitges, Marta; Bijnens, Bart H

    2015-01-01

    Time-to-peak measurements and single-parameter observations are cumbersome and often confusing for quantifying local changes in myocardial function. Recent spatiotemporal normalization techniques can provide a global picture of myocardial motion and strain patterns and overcome some of these limitations. Despite these advances, the quantification of pattern changes remains descriptive, which limits their relevance for longitudinal studies. Our paper provides a new perspective to the longitudinal analysis of myocardial motion. Non-rigid registration (diffeomorphic registration via currents) is used to match pairs of patterns, and pattern changes are inferred from the registration output. Scalability is added to the different components of the input patterns in order to tune up the contributions of the spatial, temporal and magnitude dimensions to data changes, which are of interest for our application. The technique is illustrated on 2D echocardiographic sequences from 15 patients with hypertrophic obstructive cardiomyopathy. These patients underwent biventricular pacing, which aims at provoking mechanical dyssynchrony to reduce left ventricular outflow tract (LVOT) obstruction. We demonstrate that our method can automatically quantify timing and magnitude changes in myocardial motion between baseline (non-paced) and 1 year follow-up (pacing on), resulting in a more robust analysis of complex patterns and subtle changes. Our method helps confirming that the reduction of LVOT pressure gradient actually comes from the induction of the type of dyssynchrony that was expected.

  17. Familial hypertrophic cardiomyopathy. Microsatellite haplotyping and identification of a hot spot for mutations in the beta-myosin heavy chain gene.

    PubMed

    Dausse, E; Komajda, M; Fetler, L; Dubourg, O; Dufour, C; Carrier, L; Wisnewsky, C; Bercovici, J; Hengstenberg, C; al-Mahdawi, S

    1993-12-01

    Familial hypertrophic cardiomyopathy (FHC) is a clinically and genetically heterogeneous disease. The first identified disease gene, located on chromosome 14q11-q12, encodes the beta-myosin heavy chain. We have performed linkage analysis of two French FHC pedigrees, 720 and 730, with two microsatellite markers located in the beta-myosin heavy chain gene (MYO I and MYO II) and with four highly informative markers, recently mapped to chromosome 14q11-q12. Significant linkage was found with MYO I and MYO II in pedigree 720, but results were not conclusive for pedigree 730. Haplotype analysis of the six markers allowed identification of affected individuals and of some unaffected subjects carrying the disease gene. Two novel missense mutations were identified in exon 13 by direct sequencing, 403Arg-->Leu and 403Arg-->Trp in families 720 and 730, respectively. The 403Arg-->Leu mutation was associated with incomplete penetrance, a high incidence of sudden deaths and severe cardiac events, whereas the consequences of the 403Arg-->Trp mutation appeared less severe. Haplotyping of polymorphic markers in close linkage to the beta-myosin heavy chain gene can, thus, provide rapid analysis of non informative pedigrees and rapid detection of carrier status. Our results also indicate that codon 403 of the beta-myosin heavy chain gene is a hot spot for mutations causing FHC.

  18. An explicitly solvated full atomistic model of the cardiac thin filament and application on the calcium binding affinity effects from familial hypertrophic cardiomyopathy linked mutations

    NASA Astrophysics Data System (ADS)

    Williams, Michael; Schwartz, Steven

    2015-03-01

    The previous version of our cardiac thin filament (CTF) model consisted of the troponin complex (cTn), two coiled-coil dimers of tropomyosin (Tm), and 29 actin units. We now present the newest revision of the model to include explicit solvation. The model was developed to continue our study of genetic mutations in the CTF proteins which are linked to familial hypertrophic cardiomyopathies. Binding of calcium to the cTnC subunit causes subtle conformational changes to propagate through the cTnC to the cTnI subunit which then detaches from actin. Conformational changes propagate through to the cTnT subunit, which allows Tm to move into the open position along actin, leading to muscle contraction. Calcium disassociation allows for the reverse to occur, which results in muscle relaxation. The inclusion of explicit TIP3 water solvation allows for the model to get better individual local solvent to protein interactions; which are important when observing the N-lobe calcium binding pocket of the cTnC. We are able to compare in silica and in vitro experimental results to better understand the physiological effects from mutants, such as the R92L/W and F110V/I of the cTnT, on the calcium binding affinity compared to the wild type.

  19. Dual-single photon emission computed tomography and contrast-enhanced magnetic resonance imaging to evaluate dissimilar features of apical hypertrophic cardiomyopathy.

    PubMed

    Okayama, Satoshi; Kawata, Hiroyuki; Sung, Ji Hee; Okada, Sadanori; Nishida, Taku; Onoue, Kenji; Soeda, Tsunenari; Uemura, Shiro; Saito, Yoshihiko

    2010-01-01

    Apical hypertrophic cardiomyopathy (HCM) is an uncommon variant of HCM characterized by hypertrophy located in the left ventricular apex that occurs at a rate of about 30% in the Japanese population. Although the prognosis of most patients with apical HCM is relatively benign, it can be poor if apical left ventricular aneurysms develop. However, the mechanism of aneurysmal formation is unclear. We describe two patients with apical HCM and dissimilar findings in 201Thallous chloride ((201)TlCl) and (123)I-betamethyl-p-iodophenyl-pentadecanoic acid ((123)I-BMIPP) dual single-photon emission computed tomography (dual-SPECT), but no myocardial fibrosis on contrast-enhanced magnetic resonance images (MRI). One had apparently normal myocardial perfusion and metabolism, whereas the other had exercise-induced myocardial ischemia and impaired myocardial metabolism. These findings indicated that even apical HCM without myocardial fibrosis is pathophysiologically heterogeneous. Apical HCM has been evaluated by either dual-SPECT or cardiac MRI, but not by both. Thus, a combination of imaging modalities is apparently essential for elucidating the pathophysiology of apical HCM. These dissimilar findings in dual-SPECT might be important in identifying patients with apical HCM who are at high risk of forming aneurysms.

  20. Comparison of right ventricular contractile abnormalities in hypertrophic cardiomyopathy versus hypertensive heart disease using two dimensional strain imaging: a cross-sectional study.

    PubMed

    Afonso, Luis; Briasoulis, Alex; Mahajan, Nitin; Kondur, Ashok; Siddiqui, Fayez; Siddiqui, Sabeeh; Alesh, Issa; Cardozo, Shaun; Kottam, Anupama

    2015-12-01

    Hypertrophic cardiomyopathy (HCM) affects the right ventricle (RV) because of the anatomically hypertrophied septum and plausibly by extension of the myopathic process to the RV. We sought to investigate RV strain in patients with left ventricular hypertrophy secondary to either HCM or hypertension (H-LVH). Our cross-sectional study included 32 patients with HCM, 21 patients with H-LVH, and 11 healthy subjects, who were evaluated with transthoracic echocardiography. Using a dedicated software package, bi-dimensional acquisitions were analyzed to measure segmental longitudinal strain in apical views. Right ventricular global longitudinal strain (GLS) was calculated by averaging septal and right free wall strains. The HCM and H-LVH groups were comparable for age and demographic characteristics. Right ventricular tricuspid annular plane systolic excursion was not significantly different between HCM and H-LVH subjects. Moreover, RV GLS, septal and lateral RV myocardial strain were significantly impaired in patients with HCM (all p < 0.001). Regional and global RV strain parameters were not significantly impaired in H-LVH compared to healthy controls An RV GLS cut-off value of >14.9% differentiated HCM and H-LVH with a 90% sensitivity and a 95% specificity (p < 0.001). RV strain parameters are impaired in patients with HCM. Assessment of two-dimensional RV strain parameters could help differentiate between HCM and H-LVH.

  1. Detection of a large duplication mutation in the myosin-binding protein C3 gene in a case of hypertrophic cardiomyopathy.

    PubMed

    Meyer, Thomas; Pankuweit, Sabine; Richter, Anette; Maisch, Bernhard; Ruppert, Volker

    2013-09-15

    Hypertrophic cardiomyopathy (HCM) is a cardiovascular disease with autosomal dominant inheritance caused by mutations in genes coding for sarcomeric and/or regulatory proteins expressed in cardiomyocytes. In a small cohort of HCM patients (n=8), we searched for mutations in the two most common genes responsible for HCM and found four missense mutations in the MYH7 gene encoding cardiac β-myosin heavy chain (R204H, M493V, R719W, and R870H) and three mutations in the myosin-binding protein C3 gene (MYBPC3) including one missense (A848V) and two frameshift mutations (c.3713delTG and c.702ins26bp). The c.702ins26bp insertion resulted from the duplication of a 26-bp fragment in a 54-year-old female HCM patient presenting with clinical signs of heart failure due to diastolic dysfunction. Although such large duplications (>10 bp) in the MYBPC3 gene are very rare and have been identified only in 4 families reported so far, the identical duplication mutation was found earlier in a Dutch patient, demonstrating that it may constitute a hitherto unknown founder mutation in central European populations. This observation underscores the significance of insertions into the coding sequence of the MYBPC3 gene for the development and pathogenesis of HCM.

  2. Mitochondrial Cardiomyopathies.

    PubMed

    El-Hattab, Ayman W; Scaglia, Fernando

    2016-01-01

    Mitochondria are found in all nucleated human cells and perform various essential functions, including the generation of cellular energy. Mitochondria are under dual genome control. Only a small fraction of their proteins are encoded by mitochondrial DNA (mtDNA), whereas more than 99% of them are encoded by nuclear DNA (nDNA). Mutations in mtDNA or mitochondria-related nDNA genes result in mitochondrial dysfunction leading to insufficient energy production required to meet the needs for various organs, particularly those with high energy requirements, including the central nervous system, skeletal and cardiac muscles, kidneys, liver, and endocrine system. Because cardiac muscles are one of the high energy demanding tissues, cardiac involvement occurs in mitochondrial diseases with cardiomyopathies being one of the most frequent cardiac manifestations found in these disorders. Cardiomyopathy is estimated to occur in 20-40% of children with mitochondrial diseases. Mitochondrial cardiomyopathies can vary in severity from asymptomatic status to severe manifestations including heart failure, arrhythmias, and sudden cardiac death. Hypertrophic cardiomyopathy is the most common type; however, mitochondrial cardiomyopathies might also present as dilated, restrictive, left ventricular non-compaction, and histiocytoid cardiomyopathies. Cardiomyopathies are frequent manifestations of mitochondrial diseases associated with defects in electron transport chain complexes subunits and their assembly factors, mitochondrial transfer RNAs, ribosomal RNAs, ribosomal proteins, translation factors, mtDNA maintenance, and coenzyme Q10 synthesis. Other mitochondrial diseases with cardiomyopathies include Barth syndrome, Sengers syndrome, TMEM70-related mitochondrial complex V deficiency, and Friedreich ataxia.

  3. Mitochondrial Cardiomyopathies

    PubMed Central

    El-Hattab, Ayman W.; Scaglia, Fernando

    2016-01-01

    Mitochondria are found in all nucleated human cells and perform various essential functions, including the generation of cellular energy. Mitochondria are under dual genome control. Only a small fraction of their proteins are encoded by mitochondrial DNA (mtDNA), whereas more than 99% of them are encoded by nuclear DNA (nDNA). Mutations in mtDNA or mitochondria-related nDNA genes result in mitochondrial dysfunction leading to insufficient energy production required to meet the needs for various organs, particularly those with high energy requirements, including the central nervous system, skeletal and cardiac muscles, kidneys, liver, and endocrine system. Because cardiac muscles are one of the high energy demanding tissues, cardiac involvement occurs in mitochondrial diseases with cardiomyopathies being one of the most frequent cardiac manifestations found in these disorders. Cardiomyopathy is estimated to occur in 20–40% of children with mitochondrial diseases. Mitochondrial cardiomyopathies can vary in severity from asymptomatic status to severe manifestations including heart failure, arrhythmias, and sudden cardiac death. Hypertrophic cardiomyopathy is the most common type; however, mitochondrial cardiomyopathies might also present as dilated, restrictive, left ventricular non-compaction, and histiocytoid cardiomyopathies. Cardiomyopathies are frequent manifestations of mitochondrial diseases associated with defects in electron transport chain complexes subunits and their assembly factors, mitochondrial transfer RNAs, ribosomal RNAs, ribosomal proteins, translation factors, mtDNA maintenance, and coenzyme Q10 synthesis. Other mitochondrial diseases with cardiomyopathies include Barth syndrome, Sengers syndrome, TMEM70-related mitochondrial complex V deficiency, and Friedreich ataxia. PMID:27504452

  4. Faster cross-bridge detachment and increased tension cost in human hypertrophic cardiomyopathy with the R403Q MYH7 mutation

    PubMed Central

    Witjas-Paalberends, E Rosalie; Ferrara, Claudia; Scellini, Beatrice; Piroddi, Nicoletta; Montag, Judith; Tesi, Chiara; Stienen, Ger J M; Michels, Michelle; Ho, Carolyn Y; Kraft, Theresia; Poggesi, Corrado; van der Velden, Jolanda

    2014-01-01

    The first mutation associated with hypertrophic cardiomyopathy (HCM) is the R403Q mutation in the gene encoding β-myosin heavy chain (β-MyHC). R403Q locates in the globular head of myosin (S1), responsible for interaction with actin, and thus motor function of myosin. Increased cross-bridge relaxation kinetics caused by the R403Q mutation might underlie increased energetic cost of tension generation; however, direct evidence is absent. Here we studied to what extent cross-bridge kinetics and energetics are related in single cardiac myofibrils and multicellular cardiac muscle strips of three HCM patients with the R403Q mutation and nine sarcomere mutation-negative HCM patients (HCMsmn). Expression of R403Q was on average 41 ± 4% of total MYH7 mRNA. Cross-bridge slow relaxation kinetics in single R403Q myofibrils was significantly higher (P < 0.0001) than in HCMsmn myofibrils (0.47 ± 0.02 and 0.30 ± 0.02 s−1, respectively). Moreover, compared to HCMsmn, tension cost was significantly higher in the muscle strips of the three R403Q patients (2.93 ± 0.25 and 1.78 ± 0.10 μmol l–1 s−1 kN−1 m−2, respectively) which showed a positive linear correlation with relaxation kinetics in the corresponding myofibril preparations. This correlation suggests that faster cross-bridge relaxation kinetics results in an increase in energetic cost of tension generation in human HCM with the R403Q mutation compared to HCMsmn. Therefore, increased tension cost might contribute to HCM disease in patients carrying the R403Q mutation. PMID:24928957

  5. Contractility parameters of human β-cardiac myosin with the hypertrophic cardiomyopathy mutation R403Q show loss of motor function.

    PubMed

    Nag, Suman; Sommese, Ruth F; Ujfalusi, Zoltan; Combs, Ariana; Langer, Stephen; Sutton, Shirley; Leinwand, Leslie A; Geeves, Michael A; Ruppel, Kathleen M; Spudich, James A

    2015-10-01

    Hypertrophic cardiomyopathy (HCM) is the most frequently occurring inherited cardiovascular disease. It is caused by mutations in genes encoding the force-generating machinery of the cardiac sarcomere, including human β-cardiac myosin. We present a detailed characterization of the most debated HCM-causing mutation in human β-cardiac myosin, R403Q. Despite numerous studies, most performed with nonhuman or noncardiac myosin, there is no consensus about the mechanism of action of this mutation on the function of the enzyme. We use recombinant human β-cardiac myosin and new methodologies to characterize in vitro contractility parameters of the R403Q myosin compared to wild type. We extend our studies beyond pure actin filaments to include the interaction of myosin with regulated actin filaments containing tropomyosin and troponin. We find that, with pure actin, the intrinsic force generated by R403Q is ~15% lower than that generated by wild type. The unloaded velocity is, however, ~10% higher for R403Q myosin, resulting in a load-dependent velocity curve that has the characteristics of lower contractility at higher external loads compared to wild type. With regulated actin filaments, there is no increase in the unloaded velocity and the contractility of the R403Q myosin is lower than that of wild type at all loads. Unlike that with pure actin, the actin-activated adenosine triphosphatase activity for R403Q myosin with Ca(2+)-regulated actin filaments is ~30% lower than that for wild type, predicting a lower unloaded duty ratio of the motor. Overall, the contractility parameters studied fit with a loss of human β-cardiac myosin contractility as a result of the R403Q mutation.

  6. Myosin-binding protein C DNA variants in domestic cats (A31P, A74T, R820W) and their association with Hypertrophic Cardiomyopathy

    PubMed Central

    LONGERI, M.; FERRARI, P.; KNAFELZ, P.; MEZZELANI, A.; MARABOTTI, A.; MILANESI, L.; PERTICA, G.; POLLI, M.; BRAMBILLA, P.G.; KITTLESON, M.; LYONS, L.A.; PORCIELLO, F.

    2012-01-01

    Background Two mutations in the MYBPC3 gene have been identified in Maine Coon (MCO) and Ragdoll (RD) cats with hypertrophic cardiomyopathy (HCM). Objective The present study examines the frequency of these mutations and of the A74T polymorphism to describe their worldwide distribution and correlation with echocardiography. Animals 1855 cats representing 28 breeds and random bred cats world-wide of which 446 underwent echocardiographic examination. Methods This is a prospective cross sectional study. Polymorphisms were genotyped using Illumina VeraCode GoldenGate or by direct sequencing. The disease status was defined by echocardiography according to established guidelines. Odds ratios for the joint probability of having HCM and the alleles were calculated by meta-analysis. Functional analysis was simulated. Results The MYBPC3 A31P and R820W were restricted to MCO and RD respectively. Both purebred and random bred cats had HCM and the incidence increased with age. The A74T polymorphism was not associated with any phenotype. HCM was most prevalent in MCO homozygote for the A31P mutation and the penetrance increased with age. The penetrance of the heterozygote genotype was lower (0.08) compared to the P/P genotype (0.58) in MCO. Conclusions and Clinical Importance A31P mutation occurs frequently in MCO cats. The high incidence of HCM in homozygotes for the mutation supports the causal nature of the A31P mutation. Penetrance is incomplete for heterozygotes at A31P locus, at least at a young age. The A74T variant does not appear to be correlated with HCM. PMID:23323744

  7. Effects of percutaneous transluminal septal myocardial ablation for obstructive hypertrophic cardiomyopathy on systolic and diastolic left ventricular function assessed by pressure-volume loops.

    PubMed

    Meliga, Emanuele; Steendijk, Paul; Valgimigli, Marco; Ten Cate, Folkert J; Serruys, Patrick W

    2008-04-15

    The aim of the present study was to determine the long-term effects of percutaneous transluminal septal myocardial ablation (PTSMA) on systolic and diastolic left ventricular (LV) functions in patients with obstructive hypertrophic cardiomyopathy (HC). Ten consecutive patients with symptomatic HC despite optimal medical treatment were referred for PTSMA at our center. LV systolic and diastolic functions were assessed by online LV pressure-volume loops obtained by conductance catheter at baseline and at 6 months after the procedure. At follow-up, the mean gradients at rest and after extrasystole were significantly decreased compared with baseline (88 +/- 29 to 21 +/- 11 mm Hg and 130 +/- 50 to 35 +/- 22 mm Hg, respectively, p <0.01 for the 2 comparisons). End-systolic and end-diastolic pressures significantly decreased (p <0.01), whereas end-systolic and end-diastolic LV volumes significantly increased (p <0.01 for the 2 comparisons). Cardiac output and stroke volume were unchanged, as were ejection fraction (p = 0.25) and maximum dP/dt (p = 0.13). The slope of the end-systolic pressure-volume relation was not decreased, indicating a preserved contractility. The relaxation constant time, end-diastolic stiffness, projected volume of the end-diastolic pressure-volume relation at 30 mm Hg, and diastolic stiffness constant showed a significant improvement of active and passive myocardial diastolic properties. In conclusion, PTSMA is an effective method in the treatment of symptomatic patients with HC. At 6-month follow-up, the LV-aortic gradient was decreased and active and passive LV diastolic properties were increased. Myocardial contractility was not decreased and general hemodynamics was maintained.

  8. A Green Tea Catechin Normalizes the Enhanced Ca2+ Sensitivity of Myofilaments Regulated by a Hypertrophic Cardiomyopathy Associated Mutation in Human Cardiac Troponin I (K206I)

    PubMed Central

    Warren, Chad M.; Karam, Chehade N.; Wolska, Beata M.; Kobayashi, Tomoyoshi; de Tombe, Pieter P.; Arteaga, Grace M.; Bos, J. Martijn; Ackerman, Michael J.; Solaro, R. John

    2015-01-01

    Background Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease characterized by thickening of ventricular walls and decreased left ventricular chamber volume. The majority of HCM-associated mutations are found in genes encoding sarcomere proteins. Herein, we set out to functionally characterize a novel HCM-associated mutation (K206I-TNNI3), and elucidate the mechanism of dysfunction at the level of myofilament proteins. Methods and Results The male index case was diagnosed with HCM after an out-of-hospital cardiac arrest which was followed by comprehensive clinical evaluation, transthoracic echocardiography, and clinical genetic testing. To determine molecular mechanism(s) of the mutant human cardiac troponin I (K206I), we tested the Ca2+ dependence of thin filament-activated myosin-S1-ATPase activity in a reconstituted, regulated, actomyosin system comparing wildtype human troponin complex, 50% mix of K206I/wildtype, or 100% K206I. We also exchanged native troponin detergent extracted fibers with reconstituted troponin containing either wildtype or a 65% mix of K206I/wildtype, and measured force generation. The Ca2+ sensitivity of the myofilaments containing the K206I variant was significantly increased, and when treated with 20 μM EGCG (green tea) was restored back to wildtype levels in ATPase and force measurements. The K206I mutation impairs the ability of the troponin I to inhibit ATPase activity in the absence of Ca-hcTnC (calcium-bound-human cardiac troponin C). The ability of Ca-hcTnC to neutralize the inhibition of K206I was greater than with wildtype TnI. Conclusions Compromised interactions of K206I with actin and hcTnC may lead to impaired relaxation and HCM. PMID:26553696

  9. Effects of short-term administration of verapamil on left ventricular relaxation and filling dynamics measured by a combined hemodynamic-ultrasonic technique in patients with hypertrophic cardiomyopathy.

    PubMed

    TenCate, F J; Serruys, P W; Mey, S; Roelandt, J

    1983-12-01

    The effects of short-term administration of verapamil on left ventricular isovolumetric relaxation and early and late diastolic filling dynamics were studied in 10 patients with hypertrophic cardiomyopathy by a combined hemodynamic-ultrasonic technique. Left ventricular pressures (recorded with high-fidelity micromanometers) were determined simultaneously with M mode echocardiography. After 10 mg of verapamil was given intravenously (2 mg/min), left ventricular contractility and systolic pressure dropped significantly (p less than .05). Left ventricular dP/dt fell from 1947 +/- 544 to 1489 +/- 334 mm Hg/sec, maximal velocity of the contractile element at zero load fell from 50 +/- 17 to 42 +/- 15 1/sec, peak velocity contraction of the contractile element fell from 37 +/- 10 1/sec to 29 +/- 10 1/sec (p less than .05), and left ventricular systolic pressure fell from 149 +/- 30 to 127 +/- 22 mm Hg. Left ventricular negative dP/dt increased from 1770 +/- 479 to 1477 +/- 377 mm Hg/sec (p less than .05), and the time constant of isovolumetric pressure decay was prolonged from 48 +/- 9 to 64 +/- 15 msec (p less than .05). Left ventricular end-diastolic pressure rose from 21 +/- 7 to 23 +/- 6 mm Hg (p less than .05). The time constant of isovolumetric pressure decay was calculated in three different ways, but none of these measurements was influenced by verapamil. Time of isovolumetric relaxation, duration of rapid ventricular filling, and peak rate of left ventricular lengthening were not significantly influenced by verapamil and remained highly abnormal. In contrast, peak rate of left ventricular posterior wall thinning declined further after verapamil from 2.9 +/- 1.2 to 2.4 +/- 1.4 1/sec (p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Contractility parameters of human β-cardiac myosin with the hypertrophic cardiomyopathy mutation R403Q show loss of motor function

    PubMed Central

    Nag, Suman; Sommese, Ruth F.; Ujfalusi, Zoltan; Combs, Ariana; Langer, Stephen; Sutton, Shirley; Leinwand, Leslie A.; Geeves, Michael A.; Ruppel, Kathleen M.; Spudich, James A.

    2015-01-01

    Hypertrophic cardiomyopathy (HCM) is the most frequently occurring inherited cardiovascular disease. It is caused by mutations in genes encoding the force-generating machinery of the cardiac sarcomere, including human β-cardiac myosin. We present a detailed characterization of the most debated HCM-causing mutation in human β-cardiac myosin, R403Q. Despite numerous studies, most performed with nonhuman or noncardiac myosin, there is no consensus about the mechanism of action of this mutation on the function of the enzyme. We use recombinant human β-cardiac myosin and new methodologies to characterize in vitro contractility parameters of the R403Q myosin compared to wild type. We extend our studies beyond pure actin filaments to include the interaction of myosin with regulated actin filaments containing tropomyosin and troponin. We find that, with pure actin, the intrinsic force generated by R403Q is ~15% lower than that generated by wild type. The unloaded velocity is, however, ~10% higher for R403Q myosin, resulting in a load-dependent velocity curve that has the characteristics of lower contractility at higher external loads compared to wild type. With regulated actin filaments, there is no increase in the unloaded velocity and the contractility of the R403Q myosin is lower than that of wild type at all loads. Unlike that with pure actin, the actin-activated adenosine triphosphatase activity for R403Q myosin with Ca2+-regulated actin filaments is ~30% lower than that for wild type, predicting a lower unloaded duty ratio of the motor. Overall, the contractility parameters studied fit with a loss of human β-cardiac myosin contractility as a result of the R403Q mutation. PMID:26601291

  11. Echocardiographic Characterization of a Murine Model of Hypertrophic Obstructive Cardiomyopathy Induced by Cardiac-specific Overexpression of Epidermal Growth Factor Receptor 2

    PubMed Central

    Sørensen, Lars L; Bedja, Djahida; Sysa-Shah, Polina; Liu, Hongyun; Maxwell, Amanda; Yi, Xu; Pozios, Iraklis; Olsen, Niels T; Abraham, Theodore P; Abraham, Roselle; Gabrielson, Kathleen

    2016-01-01

    Although rare, hypertrophic cardiomyopathy (HCM) with midventricular obstruction is often associated with severe symptoms and complications. None of the existing HCM animal models display this particular phenotype. Our group developed a mouse line that overexpresses the ErbB2 receptor (ErbB2tg) in cardiomyocytes; we previously showed that the ErbB2 receptor induces cardiomyocyte hypertrophy, myocyte disarray, and fibrosis compatible with HCM. In the current study, we sought to further echocardiographically characterize the ErbB2tg mouse line as a model of HCM. Compared with their wild-type littermates, ErbB2tg mice show increased left ventricular (LV) mass, concentric LV hypertrophy, and papillary muscle hypertrophy. This hypertrophy was accompanied by diastolic dysfunction, expressed as reduced E:A ratio, prolonged deceleration time, and elevated E:e′ ratio. In addition, ErbB2tg mice consistently showed midcavity obstruction with elevated LV gradients, and the flow profile revealed a prolonged pressure increase and a delayed peak, indicating dynamic obstruction. The ejection fraction was increased in ErbB2tg mice, due to reduced end-diastolic and end-systolic LV volumes. Furthermore, systolic radial strain and systolic radial strain rate but not systolic circumferential strain and longitudinal strain were decreased in ErbB2tg compared with wild-type mice. In conclusion, the phenotype of the ErbB2tg mouse model is consistent with midventricular HCM in many important aspects, including massive LV hypertrophy, diastolic dysfunction, and midcavity obstruction. This pattern is unique for a small animal model, suggesting that ErbB2tg mice may be well suited for research into the hemodynamics and treatment of this rare form of HCM. PMID:27538857

  12. [Classification of cardiomyopathy].

    PubMed

    Asakura, Masanori; Kitakaze, Masafumi

    2014-01-01

    Cardiomyopathy is a group of cardiovascular diseases with poor prognosis. Some patients with dilated cardiomyopathy need heart transplantations due to severe heart failure. Some patients with hypertrophic cardiomyopathy die unexpectedly due to malignant ventricular arrhythmias. Various phenotypes of cardiomyopathies are due to the heterogeneous group of diseases. The classification of cardiomyopathies is important and indispensable in the clinical situation. However, their classification has not been established, because the causes of cardiomyopathies have not been fully elucidated. We usually use definition and classification offered by WHO/ISFC task force in 1995. Recently, several new definitions and classifications of the cardiomyopathies have been published by American Heart Association, European Society of Cardiology and Japanese Circulation Society.

  13. Impact of left ventricular outflow tract area on systolic outflow velocity in hypertrophic cardiomyopathy: a real-time three-dimensional echocardiographic study

    NASA Technical Reports Server (NTRS)

    Qin, Jian Xin; Shiota, Takahiro; Lever, Harry M.; Rubin, David N.; Bauer, Fabrice; Kim, Yong Jin; Sitges, Marta; Greenberg, Neil L.; Drinko, Jeanne K.; Martin, Maureen; Agler, Deborah A.; Thomas, James D.

    2002-01-01

    OBJECTIVES: The aim of this study was to use real-time three-dimensional echocardiography (3DE) to investigate the quantitative relation between minimal left ventricular (LV) outflow tract area (A(LVOT)) and maximal LV outflow tract (LVOT) velocity in patients with hypertrophic obstructive cardiomyopathy (HCM). BACKGROUND: In patients with HCM, LVOT velocity should change inversely with minimal A(LVOT) unless LVOT obstruction reduces the pumping capacity of the ventricle. METHODS: A total of 25 patients with HCM with systolic anterior motion (SAM) of the mitral valve leaflets underwent real-time 3DE. The smallest A(LVOT) during systole was measured using anatomically oriented two-dimensional "C-planes" within the pyramidal 3DE volume. Maximal velocity across LVOT was evaluated by two-dimensional Doppler echocardiography (2DE). For comparison with 3DE A(LVOT), the SAM-septal distance was determined by 2DE. RESULTS: Real-time 3DE provided unique information about the dynamic SAM-septal relation during systole, with A(LVOT) ranging from 0.6 to 5.2 cm(2) (mean: 2.2 +/- 1.4 cm(2)). Maximal velocity (v) correlated inversely with A(LVOT) (v = 496 A(LVOT)(-0.80), r = -0.95, p < 0.001), but the exponent (-0.80) was significantly different from -1.0 (95% confidence interval: -0.67 to -0.92), indicating a significant impact of small A(LVOT) on the peak LVOT flow rate. By comparison, the best correlation between velocity and 2DE SAM-septal distance was significantly (p < 0.01) poorer at -0.83, indicating the superiority of 3DE for assessing A(LVOT). CONCLUSIONS: Three-dimensional echocardiography-measured A(LVOT) provides an assessment of HCM geometry that is superior to 2DE methods. These data indicate that the peak LVOT flow rate appears to be significantly decreased by reduced A(LVOT). Real-time 3DE is a potentially valuable clinical tool for assessing patients with HCM.

  14. High Spatial Resolution Cardiovascular Magnetic Resonance at 7.0 Tesla in Patients with Hypertrophic Cardiomyopathy – First Experiences: Lesson Learned from 7.0 Tesla

    PubMed Central

    Prothmann, Marcel; von Knobelsdorff-Brenkenhoff, Florian; Töpper, Agnieszka; Dieringer, Matthias A.; Shahid, Etham; Graessl, Andreas; Rieger, Jan; Lysiak, Darius; Thalhammer, C.; Huelnhagen, Till; Kellman, Peter; Niendorf, Thoralf; Schulz-Menger, Jeanette

    2016-01-01

    Background Cardiovascular Magnetic Resonance (CMR) provides valuable information in patients with hypertrophic cardiomyopathy (HCM) based on myocardial tissue differentiation and the detection of small morphological details. CMR at 7.0T improves spatial resolution versus today’s clinical protocols. This capability is as yet untapped in HCM patients. We aimed to examine the feasibility of CMR at 7.0T in HCM patients and to demonstrate its capability for the visualization of subtle morphological details. Methods We screened 131 patients with HCM. 13 patients (9 males, 56 ±31 years) and 13 healthy age- and gender-matched subjects (9 males, 55 ±31years) underwent CMR at 7.0T and 3.0T (Siemens, Erlangen, Germany). For the assessment of cardiac function and morphology, 2D CINE imaging was performed (voxel size at 7.0T: (1.4x1.4x2.5) mm3 and (1.4x1.4x4.0) mm3; at 3.0T: (1.8x1.8x6.0) mm3). Late gadolinium enhancement (LGE) was performed at 3.0T for detection of fibrosis. Results All scans were successful and evaluable. At 3.0T, quantification of the left ventricle (LV) showed similar results in short axis view vs. the biplane approach (LVEDV, LVESV, LVMASS, LVEF) (p = 0.286; p = 0.534; p = 0.155; p = 0.131). The LV-parameters obtained at 7.0T where in accordance with the 3.0T data (pLVEDV = 0.110; pLVESV = 0.091; pLVMASS = 0.131; pLVEF = 0.182). LGE was detectable in 12/13 (92%) of the HCM patients. High spatial resolution CINE imaging at 7.0T revealed hyperintense regions, identifying myocardial crypts in 7/13 (54%) of the HCM patients. All crypts were located in the LGE-positive regions. The crypts were not detectable at 3.0T using a clinical protocol. Conclusions CMR at 7.0T is feasible in patients with HCM. High spatial resolution gradient echo 2D CINE imaging at 7.0T allowed the detection of subtle morphological details in regions of extended hypertrophy and LGE. PMID:26863618

  15. Genetic anticipation in a special form of hypertrophic cardiomyopathy with sudden cardiac death in a family with 74 members across 5 generations

    PubMed Central

    Guo, Xiying; Fan, Chaomei; Wang, Yanping; Wang, Miao; Cai, Chi; Yang, Yinjian; Zhao, Shihua; Duan, Fujian; Li, Yishi

    2017-01-01

    Abstract Hypertrophic cardiomyopathy (HCM) is the most common heritable heart disease. The genetic anticipation of HCM and its associated etiology, sudden cardiac death (SCD), remains unclear. The aim of this study was to investigate the mechanism underlying the genetic anticipation of HCM and associated SCD. An HCM family including 5 generations and 74 members was studied. Two-dimensional echocardiography was performed to diagnose HCM. The age of onset of HCM was defined as the age at first diagnosis according to hospital records. The information on SCD was confirmed by verification by ≥2 family members and a review of hospital records. Whole-genome sequencing was performed on 4 HCM subjects and 1 healthy control in the family. The identified mutations were screened in all available family members and 216 unrelated healthy controls by Sanger sequencing. The median ages of onset of HCM were 63.5, 38.5, and 18.0 years in members of the second, third, and fourth generations of the family, respectively, and the differences between the generations were significant (P < 0.001). The age at SCD also decreased with each subsequent generation (P < 0.05). In particular, among the third-generation family members, SCD occurred between 30 and 40 years of age at approximately 8 am, whereas among the fourth-generation family members, all 5 males who experienced SCD were 16 years of age and died at approximately 8 am. The sarcomere gene mutations MYH7-A719H and MYOZ2-L169G were detected in the HCM individuals in this pedigree. Increases in the number of mutations and the frequency of multiple gene mutations were observed in the younger generations. Moreover, a structural variant was present in the HCM phenotype–positive subjects but was absent in the HCM phenotype–negative subjects. HCM may exhibit genetic anticipation, with a decreased age of onset and increased severity in successive generations. Multiple gene mutations may contribute to genetic anticipation in HCM

  16. Inherited cardiomyopathies mimicking arrhythmogenic right ventricular cardiomyopathy.

    PubMed

    Roberts, Jason D; Veinot, John P; Rutberg, Julie; Gollob, Michael H

    2010-01-01

    Arrhythmogenic right ventricular cardiomyopathy (ARVC) represents an inherited cardiomyopathy that manifests clinically with malignant ventricular arrhythmias, sudden cardiac death, and less commonly heart failure. The condition is characterized by replacement of the myocardium, primarily of the right ventricle, with fibrofatty tissue. Extensive fibrofatty replacement of the myocardium has been previously thought to be pathognomonic of ARVC; however, this report details two other forms of inherited cardiomyopathy, namely hypertrophic cardiomyopathy (HCM) and the PRKAG2 cardiac syndrome, that were found to have significant fibrofatty myocardial replacement at pathologic examination. This report represents the first documentation of inherited cardiomyopathies mimicking ARVC and highlights the concept that other cardiac conditions can be associated with fibrofatty replacement of the myocardium.

  17. Genetics of restrictive cardiomyopathy.

    PubMed

    Sen-Chowdhry, Srijita; Syrris, Petros; McKenna, William J

    2010-04-01

    Restrictive physiology, a severe form of diastolic dysfunction, is characteristically observed in the setting of constrictive pericarditis and myocardial restriction. The latter is commonly due to systemic diseases, some of which are inherited as mendelian traits (eg, hereditary amyloidosis), while others are multifactorial (eg, sarcoidosis). When restrictive physiology occurs as an early and dominant feature of a primary myocardial disorder, it may be termed restrictive cardiomyopathy. In the past decade, clinical and genetic studies have demonstrated that restrictive cardiomyopathy as such is part of the spectrum of sarcomeric disease and frequently coexists with hypertrophic cardiomyopathy in affected families.

  18. [Gender effect on cardiomyopathy].

    PubMed

    Biagini, Elena; Berardini, Alessandra; Graziosi, Maddalena; Rosmini, Stefania; Pazzi, Chiara; Rapezzi, Claudio

    2012-06-01

    The role of a gender effect (that means differences in clinical manifestations, access to therapies and response to treatments according to gender) in cardiomyopathies remains a matter of debate. Although recent studies have evaluated the differences in the clinical features and prognosis between the two sexes, many issues remain to be elucidated. At present, the only sex-specific condition that affects females is peripartum cardiomyopathy. Recent evidence suggests a pathogenetic role of a prolactin derivative, and ongoing clinical trials are investigating the possibility of targeted therapies using prolactin secretion inhibitors, such as bromocriptine and carbegoline. Although women were considered so far only carriers of X-linked diseases (Anderson-Fabry disease, Danon disease, Hunter syndrome and dystrophinopathies), clinical experience showed a wide spectrum of clinical manifestations in females due to random X chromosome inactivation. Conversely, in mitochondrial diseases (with matrilineal inheritance), cardiomyopathies may occur in the context of clinical multisystemic involvement without significant gender-related differences. Autosomal inherited cardiomyopathies also show different phenotypes and prognostic impact according to gender. The hypothesis of a premenopausal protective role of female hormones towards myocardial involvement has been raised by recent data on transtiretin-related amyloidosis and hypertrophic cardiomyopathy. Preexisting cardiomyopathies may affect pregnancy, labor and delivery in women, since all these conditions are associated with important hemodynamic changes. Women with low-risk hypertrophic cardiomyopathy (asymptomatic and without left ventricular outflow tract gradient) usually can tolerate pregnancy. Conversely, women who are symptomatic before pregnancy or have severe hypertrophy with important outflow tract gradient are at higher risk and should be referred to a tertiary center to be evaluated on a case by case basis

  19. Pregnancy, cardiomyopathies, and genetics.

    PubMed

    Van Tintelen, J Peter; Pieper, Petronella G; Van Spaendonck-Zwarts, Karin Y; Van Den Berg, Maarten P

    2014-03-15

    Although familial forms of cardiomyopathy such as hypertrophic or dilated cardiomyopathy have been recognized for decades, it is only recently that much of the genetic basis of these inherited cardiomyopathies has been elucidated. This has provided important insights into the pathophysiological mechanisms underlying the disease phenotype. This increased knowledge and the availability of genetic testing has resulted in increasing numbers of mutation carriers who are being monitored, including many who are now of child-bearing age. Pregnancy is generally well tolerated in asymptomatic patients or mutation carriers with inherited cardiomyopathies. However, since pregnancy leads to major physiological changes in the cardiovascular system, in women with genetic cardiomyopathies or who carry a mutation pre-disposing to a genetic cardiomyopathy, pregnancy entails a risk of developing heart failure and/or arrhythmias. This deterioration of cardiac function may occur despite optimal medical treatment. Advanced left ventricular dysfunction, poor functional class (NYHA class III or IV), or prior cardiac events appear to increase the risk of maternal cardiac complications. However, there are no large series of cardiomyopathy patients who are regularly evaluated for cardiac complications during pregnancy and for certain types of inherited cardiomyopathy, only case reports on individual pregnancies are available. Pre-conception cardiologic evaluation and genetic counselling are important for every woman with a cardiomyopathy or a cardiomyopathy-related mutation who is considering having a family. In this article, we give an overview of the basic clinical aspects, genetics, and pregnancy outcome in women with different types of inherited cardiomyopathies. We also discuss the genetic aspects of pregnancy-associated cardiomyopathy, including peripartum cardiomyopathy.

  20. Mechanical aberrations in hypetrophic cardiomyopathy: emerging concepts

    PubMed Central

    Ntelios, Dimitrios; Tzimagiorgis, Georgios; Efthimiadis, Georgios K.; Karvounis, Haralambos

    2015-01-01

    Hypertrophic cardiomyopathy is the most common monogenic disorder in cardiology. Despite important advances in understanding disease pathogenesis, it is not clear how flaws in individual sarcomere components are responsible for the observed phenotype. The aim of this article is to provide a brief interpretative analysis of some currently proposed pathophysiological mechanisms of hypertrophic cardiomyopathy, with a special emphasis on alterations in the cardiac mechanical properties. PMID:26347658

  1. Human junctophilin-2 undergoes a structural rearrangement upon binding PtdIns(3,4,5)P3 and the S101R mutation identified in hypertrophic cardiomyopathy obviates this response.

    PubMed

    Bennett, Hayley J; Davenport, John Bernard; Collins, Richard F; Trafford, Andrew W; Pinali, Christian; Kitmitto, Ashraf

    2013-12-01

    JP2 (junctophilin-2) is believed to hold the transverse tubular and jSR (junctional sarcoplasmic reticulum) membranes in a precise geometry that facilitates excitation-contraction coupling in cardiomyocytes. We have expressed and purified human JP2 and shown using electron microscopy that the protein forms elongated structures ~15 nm long and 2 nm wide. Employing lipid-binding assays and quartz crystal microbalance with dissipation we have determined that JP2 is selective for PS (phosphatidylserine), with a Kd value of ~0.5 μM, with the N-terminal domain mediating this interaction. JP2 also binds PtdIns(3,4,5)P3 at a different site than PS, resulting in the protein adopting a more flexible conformation; this interaction is modulated by both Ca(2+) and Mg(2+) ions. We show that the S101R mutation identified in patients with hypertrophic cardiomyopathy leads to modification of the protein secondary structure, forming a more flexible molecule with an increased affinity for PS, but does not undergo a structural transition in response to binding PtdIns(3,4,5)P3. In conclusion, the present study provides new insights into the structural and lipid-binding properties of JP2 and how the S101R mutation may have an effect upon the stability of the dyad organization with the potential to alter JP2-protein interactions regulating Ca(2+) cycling.

  2. Preoperative preparation of patients with cardiomyopathies in non-cardiac surgery.

    PubMed

    Bradić, Zeljko; Ivanović, Branislava; Marković, Dejan; Simić, Dusica; Janković, Radmilo; Kalezić, Nevena

    2011-01-01

    Cardiomyopathies are myocardial diseases in which there is structural and functional disorder of the heart muscle, in the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease. Cardiomyopathies are grouped into specific morphological and functional phenotypes: dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and unclassified cardiomyopathies. Patients with dilated and hypertrophic cardiomypathy are prone to the development of congestive heart failure in the perioperative period. Also, patients with hypertrophic and arrhythmogenic right ventricular cardiomyopathy are prone to arrhythmias in the perioperative period. Preoperative evaluation includes history, physical examination, ECG, chest radiography, complete blood count, electrolytes, creatinine, glomerular filtration rate, glucose, liver enzymes, urin analysis, BNP and echocardiographic evaluation of left ventricular function. Drug therapy should be optimized and continued preoperatively. Surgery should be delayed (unless urgent) in patients with decompensated or untreated cardiomyopathy. Preoperative evaluation requires integrated multidisciplinary approach of anesthesiologists, cardiologist and surgeons.

  3. Identification and Functional Characterization of a Novel CACNA1C-Mediated Cardiac Disorder Characterized by Prolonged QT Intervals with Hypertrophic Cardiomyopathy, Congenital Heart Defects, and Sudden Cardiac Death

    PubMed Central

    Boczek, Nicole J.; Ye, Dan; Jin, Fang; Tester, David J.; Huseby, April; Bos, J. Martijn; Johnson, Aaron J.; Kanter, Ronald; Ackerman, Michael J.

    2016-01-01

    Background A portion of sudden cardiac deaths (SCD) can be attributed to structural heart diseases such as hypertrophic cardiomyopathy (HCM) or cardiac channelopathies such as long QT syndrome (LQTS); however, the underlying molecular mechanisms are quite distinct. Here, we identify a novel CACNA1C missense mutation with mixed loss-of-function/gain-of-function responsible for a complex phenotype of LQTS, HCM, SCD, and congenital heart defects (CHDs). Methods and Results Whole exome sequencing (WES) in combination with Ingenuity Variant Analysis was completed on three affected individuals and one unaffected individual from a large pedigree with concomitant LQTS, HCM, and CHDs and identified a novel CACNA1C mutation, p.Arg518Cys, as the most likely candidate mutation. Mutational analysis of exon 12 of CACNA1C was completed on 5 additional patients with a similar phenotype of LQTS plus a personal or family history of HCM-like phenotypes, and identified two additional pedigrees with mutations at the same position, p.Arg518Cys/His. Whole cell patch clamp technique was used to assess the electrophysiological effects of the identified mutations in CaV1.2, and revealed a complex phenotype, including loss of current density and inactivation in combination with increased window and late current. Conclusions Through WES and expanded cohort screening, we identified a novel genetic substrate p.Arg518Cys/His-CACNA1C, in patients with a complex phenotype including LQTS, HCM, and CHDs annotated as cardiac-only Timothy syndrome. Our electrophysiological studies, identification of mutations at the same amino acid position in multiple pedigrees, and co-segregation with disease in these pedigrees provides evidence that p.Arg518Cys/His is the pathogenic substrate for the observed phenotype. PMID:26253506

  4. Prevalence and Phenotypic Expression of Mutations in the MYH7, MYBPC3 and TNNT2 Genes in Families with Hypertrophic Cardiomyopathy in the South of Brazil: A Cross-Sectional Study

    PubMed Central

    Mattos, Beatriz Piva e; Scolari, Fernando Luís; Torres, Marco Antonio Rodrigues; Simon, Laura; de Freitas, Valéria Centeno; Giugliani, Roberto; Matte, Úrsula

    2016-01-01

    Background: Mutations in sarcomeric genes are found in 60-70% of individuals with familial forms of hypertrophic cardiomyopathy (HCM). However, this estimate refers to northern hemisphere populations. The molecular-genetic profile of HCM has been subject of few investigations in Brazil, particularly in the south of the country. Objective: To investigate mutations in the sarcomeric genes MYH7, MYBPC3 and TNNT2 in a cohort of HCM patients living in the extreme south of Brazil, and to evaluate genotype-phenotype associations. Methods: Direct DNA sequencing of all encoding regions of three sarcomeric genes was conducted in 43 consecutive individuals of ten unrelated families. Results: Mutations for CMH have been found in 25 (58%) patients of seven (70%) of the ten study families. Fourteen (56%) individuals were phenotype-positive. All mutations were missense, four (66%) in MYH7 and two (33%) in MYBPC3. We have not found mutations in the TNNT2 gene. Mutations in MYH7 were identified in 20 (47%) patients of six (60%) families. Two of them had not been previously described. Mutations in MYBPC3 were found in seven (16%) members of two (20%) families. Two (5%) patients showed double heterozygosis for both genes. The mutations affected different domains of encoded proteins and led to variable phenotypic expression. A family history of HCM was identified in all genotype-positive individuals. Conclusions: In this first genetic-molecular analysis carried out in the south of Brazil, we found mutations in the sarcomeric genes MYH7 and MYBPC3 in 58% of individuals. MYH7-related disease was identified in the majority of cases with mutation. PMID:27737317

  5. [Hereditary cardiomyopathies: a review. Mutation of structural proteins a common cause of hereditary cardiomyopathy].

    PubMed

    Sjöberg, Gunnar; Kostareva, Anna; Sejersen, Thomas

    Cardiomyopathy is a disorder of the cardiac muscle and can be either primary or secondary. The primary disorders have been classified by WHO into 4 groups based on structure and function; hypertrophic, dilated and restricted cardiomyopathies and arrythmogenic right ventricle dysplasia. During the last decade the familial nature of many of these cardiomyopathies has been elucidated and different genes have been found to be mutated and causative of disease. Certain patterns can be distinguished in the mutated genes, e.g. in general the genes causing hypertrophic cardiomyopathies code for proteins involved in the contractile apparatus, the sarcomere, and the genes causing dilated cardiomyopathy code for proteins that anchor the sarcomere to the cell membrane and extracellular matrix. This article reviews these recent genetic findings and discusses their potential clinical applicability.

  6. Restrictive cardiomyopathy

    MedlinePlus

    Cardiomyopathy - restrictive; Infiltrative cardiomyopathy; Idiopathic myocardial fibrosis ... In a case of restrictive cardiomyopathy, the heart muscle is of normal size or slightly enlarged. Most of the time, it also pumps normally. However, it does ...

  7. Evolving Approaches to Genetic Evaluation of Specific Cardiomyopathies.

    PubMed

    Teo, Loon Yee Louis; Moran, Rocio T; Tang, W H Wilson

    2015-12-01

    The understanding of the genetic basis of cardiomyopathy has expanded significantly over the past 2 decades. The increasing availability, shortening diagnostic time, and lowering costs of genetic testing have provided researchers and physicians with the opportunity to identify the underlying genetic determinants for thousands of genetic disorders, including inherited cardiomyopathies, in effort to improve patient morbidities and mortality. As such, genetic testing has advanced from basic scientific research to clinical application and has been incorporated as part of patient evaluations for suspected inherited cardiomyopathies. Genetic evaluation framework of inherited cardiomyopathies typically encompasses careful evaluation of family history, genetic counseling, clinical screening of family members, and if appropriate, molecular genetic testing. This review summarizes the genetics, current guideline recommendations, and evidence supporting the genetic evaluation framework of five hereditary forms of cardiomyopathy: dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), restrictive cardiomyopathy (RCM), and left ventricular noncompaction (LVNC).

  8. Importance of genetic evaluation and testing in pediatric cardiomyopathy.

    PubMed

    Tariq, Muhammad; Ware, Stephanie M

    2014-11-26

    Pediatric cardiomyopathies are clinically heterogeneous heart muscle disorders that are responsible for significant morbidity and mortality. Phenotypes include hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy, left ventricular noncompaction and arrhythmogenic right ventricular cardiomyopathy. There is substantial evidence for a genetic contribution to pediatric cardiomyopathy. To date, more than 100 genes have been implicated in cardiomyopathy, but comprehensive genetic diagnosis has been problematic because of the large number of genes, the private nature of mutations, and difficulties in interpreting novel rare variants. This review will focus on current knowledge on the genetic etiologies of pediatric cardiomyopathy and their diagnostic relevance in clinical settings. Recent developments in sequencing technologies are greatly impacting the pace of gene discovery and clinical diagnosis. Understanding the genetic basis for pediatric cardiomyopathy and establishing genotype-phenotype correlations may help delineate the molecular and cellular events necessary to identify potential novel therapeutic targets for heart muscle dysfunction in children.

  9. Cardiomyopathy in pregnancy.

    PubMed

    Lewey, Jennifer; Haythe, Jennifer

    2014-08-01

    Cardiomyopathy during pregnancy is uncommon but potentially catastrophic to maternal health, accounting for up to 11% of maternal deaths. Peripartum cardiomyopathy is diagnosed in women without a history of heart disease 1 month before delivery or within 5 months postpartum. About half of all women will have full myocardial recovery within 6 months of diagnosis, but complications such as severe heart failure or death are not rare. African-American women have higher rates of diagnosis and adverse events. Women with preexisting cardiomyopathy, such as dilated or hypertrophic cardiomyopathy, followed closely during pregnancy often tolerate pregnancy and delivery. Risk factors for adverse outcomes include functional status at baseline, severity of systolic dysfunction or outflow tract gradient, or history of prior cardiac event, such as arrhythmia or stroke. The level of brain natriuretic peptide (BNP) can be used to risk stratify women for adverse events. Pregnant women with cardiomyopathy should be followed closely by a multidisciplinary team comprised of nurses, obstetricians, neonatologists, cardiologists, anesthesiologists, and cardiac surgeons.

  10. Calcium Ions in Inherited Cardiomyopathies.

    PubMed

    Deftereos, Spyridon; Papoutsidakis, Nikolaos; Giannopoulos, Georgios; Angelidis, Christos; Raisakis, Konstantinos; Bouras, Georgios; Davlouros, Periklis; Panagopoulou, Vasiliki; Goudevenos, John; Cleman, Michael W; Lekakis, John

    2016-01-01

    Inherited cardiomyopathies are a known cause of heart failure, although the pathways and mechanisms leading from mutation to the heart failure phenotype have not been elucidated. There is strong evidence that this transition is mediated, at least in part, by abnormal intracellular Ca(2+) handling, a key ion in ventricular excitation, contraction and relaxation. Studies in human myocytes, animal models and in vitro reconstituted contractile protein complexes have shown consistent correlations between Ca(2+) sensitivity and cardiomyopathy phenotype, irrespective of the causal mutation. In this review we present the available data about the connection between mutations linked to familial hypertrophic (HCM), dilated (DCM) and restrictive (RCM) cardiomyopathy, right ventricular arrhythmogenic cardiomyopathy/dysplasia (ARVC/D) as well as left ventricular non-compaction and the increase or decrease in Ca(2+) sensitivity, together with the results of attempts to reverse the manifestation of heart failure by manipulating Ca(2+) homeostasis.

  11. Molecular etiology of idiopathic cardiomyopathy

    PubMed Central

    Arimura, T; Hayashi, T; Kimura, A

    2007-01-01

    Summary Idiopathic cardiomyopathy (ICM) is a primary cardiac disorder associated with abnormalities of ventricular wall thickness, size of ventricular cavity, contraction, relaxation, conduction and rhythm. Over the past two decades, molecular genetic analyses have revealed that mutations in the various genes cause ICM and such information concerning the genetic basis of ICM enables us to speculate the pathogenesis of this heterogeous cardiac disease. This review focuses on the molecular pathogenesis, i.e., genetic abnormalities and functional alterations due to the mutations especially in sarcomere/cytoskeletal components, in three characteristic features of ICM, hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) and restrictive cardiomyopathy (RCM). Understanding the functional abnormalities of the sarcomere/cytoskeletal components, in ICM, has unraveled the function of these components not only as a contractile unit but also as a pivot for transduction of biochemical signals. PMID:18646564

  12. Evolving molecular diagnostics for familial cardiomyopathies: at the heart of it all.

    PubMed

    Callis, Thomas E; Jensen, Brian C; Weck, Karen E; Willis, Monte S

    2010-04-01

    Cardiomyopathies are an important and heterogeneous group of common cardiac diseases. An increasing number of cardiomyopathies are now recognized to have familial forms, which result from single-gene mutations that render a Mendelian inheritance pattern, including hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and left ventricular noncompaction cardiomyopathy. Recently, clinical genetic tests for familial cardiomyopathies have become available for clinicians evaluating and treating patients with these diseases, making it necessary to understand the current progress and challenges in cardiomyopathy genetics and diagnostics. In this review, we summarize the genetic basis of selected cardiomyopathies, describe the clinical utility of genetic testing for cardiomyopathies and outline the current challenges and emerging developments.

  13. Psychological disorders in adults with inherited cardiomyopathies and Takotsubo syndrome.

    PubMed

    Suárez Bagnasco, Mariana; Núñez-Gil, Iván J

    2016-06-03

    We performed a narrative review about psychological disorders in adults with Takotsubo syndrome and inherited cardiomyopathies. Through the electronic database PubMed and PsycINFO we searched all relevant related manuscripts published between 2000 and 2015. We found twelve studies that explore psychological disorders in Takotsubo syndrome and eight about inherited cardiomyopathies: five enrolled patients with hypertrophic cardiomyopathy, two dilated cardiomyopathy, and one arrhythmogenic right ventricular cardiomyopathy. All papers reported the presence of psychological disorders. In Takotsubo syndrome, depression fluctuates between 20.5 and 48% and anxiety was present among 26 and 56%. A study reported that anxiety increases the probability of developing Takotsubo syndrome. In dilated cardiomyopathy, anxiety was present in 50% and depression in 22%. In arrhythmogenic right ventricular cardiomyopathy, younger age, poorer functional capacity and having experienced at least one implantable cardioverter defibrillator shock, were significant independent predictors of both device-specific and generalized anxiety. In hypertrophic cardiomyopathy, anxiety and depression were present in 45.2% and 17.9%, respectively. Thirty seven percent met diagnostic criteria for anxiety disorders and 21% for mood disorders. Nearby half hypertrophic cardiomyopathy patients report triggering of chest pain, dyspnea, and dizziness by emotional stress. Due to the small number of studies, conclusions are limited. However, we discuss some results.

  14. Myocardial mechanics in cardiomyopathies.

    PubMed

    Modesto, Karen; Sengupta, Partho P

    2014-01-01

    Cardiomyopathies are a heterogeneous group of diseases that can be phenotypically recognized by specific patterns of ventricular morphology and function. The authors summarize recent clinical observations that mechanistically link the multidirectional components of left ventricular (LV) deformation with morphological phenotypes of cardiomyopathies for offering key insights into the transmural heterogeneity of myocardial function. Subendocardial dysfunction predominantly alters LV longitudinal shortening, lengthening and suction performance and contributes to the phenotypic patterns of heart failure (HF) with preserved ejection fraction (EF) seen with hypertrophic and restrictive patterns of cardiomyopathy. On the other hand, a more progressive transmural disease results in reduction of LV circumferential and twist mechanics leading to the phenotypic pattern of dilated cardiomyopathy and the clinical syndrome of HF with reduced (EF). A proper characterization of LV transmural mechanics, energetics, and space-time distributions of pressure and shear stress may allow recognition of early functional changes that can forecast progression or reversal of LV remodeling. Furthermore, the interactions between LV muscle and fluid mechanics hold the promise for offering newer mechanistic insights and tracking impact of novel therapies.

  15. Peripartum cardiomyopathy.

    PubMed

    Grixti, Sarah; Magri, Caroline J; Xuereb, Robert; Fava, Stephen

    2015-02-01

    Peripartum cardiomyopathy is a form of dilated cardiomyopathy of indeterminate aetiology occurring in late pregnancy or the months following delivery. This article reviews current knowledge of its pathophysiology, therapeutic strategies and prognosis, as well as new treatments and future directions.

  16. Cardiomyopathy in a dish: using human inducible pluripotent stem cells to model inherited cardiomyopathies.

    PubMed

    Kamdar, Forum; Klaassen Kamdar, Andre; Koyano-Nakagawa, Naoko; Garry, Mary G; Garry, Daniel J

    2015-09-01

    Inherited cardiomyopathies, including hypertrophic cardiomyopathy, dilated cardiomyopathies, arrythmogenic right ventricular cardiomyopathy, and other inherited forms of heart failure, represent a unique set of genetically defined cardiovascular disease processes. Unraveling the molecular mechanisms of these deadly forms of human heart disease has been challenging, but recent groundbreaking scientific advances in stem cell technology have allowed for the generation of patient-specific human inducible stem cell (hiPSC)-derived cardiomyocytes (CMs). hiPSC-derived CMs retain the genetic blueprint of the patient, they can be maintained in culture, and they recapitulate the phenotypic characteristics of the disease in vitro, thus serving as a disease in a dish. This review provides an overview of in vitro modeling of inherited cardiomyopathies with the use of patient-specific hiPSC-derived CMs.

  17. Genetic Variations Leading to Familial Dilated Cardiomyopathy.

    PubMed

    Cho, Kae Won; Lee, Jongsung; Kim, Youngjo

    2016-10-01

    Cardiomyopathy is a major cause of death worldwide. Based on pathohistological abnormalities and clinical manifestation, cardiomyopathies are categorized into several groups: hypertrophic, dilated, restricted, arrhythmogenic right ventricular, and unclassified. Dilated cardiomyopathy, which is characterized by dilation of the left ventricle and systolic dysfunction, is the most severe and prevalent form of cardiomyopathy and usually requires heart transplantation. Its etiology remains unclear. Recent genetic studies of single gene mutations have provided significant insights into the complex processes of cardiac dysfunction. To date, over 40 genes have been demonstrated to contribute to dilated cardiomyopathy. With advances in genetic screening techniques, novel genes associated with this disease are continuously being identified. The respective gene products can be classified into several functional groups such as sarcomere proteins, structural proteins, ion channels, and nuclear envelope proteins. Nuclear envelope proteins are emerging as potential molecular targets in dilated cardiomyopathy. Because they are not directly associated with contractile force generation and transmission, the molecular pathways through which these proteins cause cardiac muscle disorder remain unclear. However, nuclear envelope proteins are involved in many essential cellular processes. Therefore, integrating apparently distinct cellular processes is of great interest in elucidating the etiology of dilated cardiomyopathy. In this mini review, we summarize the genetic factors associated with dilated cardiomyopathy and discuss their cellular functions.

  18. Genetic Variations Leading to Familial Dilated Cardiomyopathy

    PubMed Central

    Cho, Kae Won; Lee, Jongsung; Kim, Youngjo

    2016-01-01

    Cardiomyopathy is a major cause of death worldwide. Based on pathohistological abnormalities and clinical manifestation, cardiomyopathies are categorized into several groups: hypertrophic, dilated, restricted, arrhythmogenic right ventricular, and unclassified. Dilated cardiomyopathy, which is characterized by dilation of the left ventricle and systolic dysfunction, is the most severe and prevalent form of cardiomyopathy and usually requires heart transplantation. Its etiology remains unclear. Recent genetic studies of single gene mutations have provided significant insights into the complex processes of cardiac dysfunction. To date, over 40 genes have been demonstrated to contribute to dilated cardiomyopathy. With advances in genetic screening techniques, novel genes associated with this disease are continuously being identified. The respective gene products can be classified into several functional groups such as sarcomere proteins, structural proteins, ion channels, and nuclear envelope proteins. Nuclear envelope proteins are emerging as potential molecular targets in dilated cardiomyopathy. Because they are not directly associated with contractile force generation and transmission, the molecular pathways through which these proteins cause cardiac muscle disorder remain unclear. However, nuclear envelope proteins are involved in many essential cellular processes. Therefore, integrating apparently distinct cellular processes is of great interest in elucidating the etiology of dilated cardiomyopathy. In this mini review, we summarize the genetic factors associated with dilated cardiomyopathy and discuss their cellular functions. PMID:27802374

  19. Peripartum Cardiomyopathy.

    PubMed

    Arany, Zolt; Elkayam, Uri

    2016-04-05

    Peripartum cardiomyopathy is a potentially life-threatening pregnancy-associated disease that typically arises in the peripartum period and is marked by left ventricular dysfunction and heart failure. The disease is relatively uncommon, but its incidence is rising. Women often recover cardiac function, but long-lasting morbidity and mortality are not infrequent. Management of peripartum cardiomyopathy is largely limited to the same neurohormonal antagonists used in other forms of cardiomyopathy, and no proven disease-specific therapies exist yet. Research in the past decade has suggested that peripartum cardiomyopathy is caused by vascular dysfunction, triggered by late-gestational maternal hormones. Most recently, information has also indicated that many cases of peripartum cardiomyopathy have genetic underpinnings. We review here the known epidemiology, clinical presentation, and management of peripartum cardiomyopathy, as well as the current knowledge of the pathophysiology of the disease.

  20. Doxorubicin Cardiomyopathy

    PubMed Central

    Chatterjee, Kanu; Zhang, Jianqing; Honbo, Norman; Karliner, Joel S.

    2010-01-01

    Established doxorubicin cardiomyopathy is a lethal disease. When congestive heart failure develops, mortality is approximately 50%. Extensive research has been done to understand the mechanism and pathophysiology of doxorubicin cardiomyopathy, and considerable knowledge and experience has been gained. Unfortunately, no effective treatment for established doxorubicin cardiomyopathy is presently available. Extensive research has been done and is being done to discover preventive treatments. However an effective and clinically applicable preventive treatment is yet to be discovered. PMID:20016174

  1. Clinical Characteristics and Treatment of Cardiomyopathies in Children.

    PubMed

    Price, Jack F; Jeewa, Aamir; Denfield, Susan W

    2016-01-01

    Cardiomyopathies are diseases of the heart muscle, a term introduced in 1957 to identify a group of myocardial diseases not attributable to coronary artery disease. The definition has since been modified to refer to structural and or functional abnormalities of the myocardium where other known causes of myocardial dysfunction, such as systemic hypertension, valvular disease and ischemic heart disease, have been excluded. In this review, we discuss the pathophysiology, clinical assessment and therapeutic strategies for hypertrophic, dilated and hypertrophic cardiomyopathies, with a particular focus on aspects unique to children.

  2. Systematic review of pregnancy in women with inherited cardiomyopathies.

    PubMed

    Krul, Sébastien P J; van der Smagt, Jasper J; van den Berg, Maarten P; Sollie, Krystyna M; Pieper, Petronella G; van Spaendonck-Zwarts, Karin Y

    2011-06-01

    Pregnancy exposes women with inherited cardiomyopathies to increased risk for heart failure and arrhythmias. In this paper, we review the clinical course and management of pregnant women with the following inherited cardiomyopathies: hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, left ventricular non-compaction cardiomyopathy, and restrictive cardiomyopathy. We also discuss peripartum cardiomyopathy. Pregnancy is generally well tolerated in asymptomatic patients with inherited cardiomyopathies. However, worsening of the clinical condition can occur during pregnancy, despite intensive medical treatment. If prior cardiac events, poor functional class (New York Heart Association class III or IV), or advanced left ventricular systolic dysfunction are present, the risk of maternal cardiac complications during pregnancy are markedly increased. The postpartum condition is generally no worse than the antepartum condition, but no long-term follow-up studies have been reported. Preconception evaluation and counselling are important aspects of managing women with inherited cardiomyopathies. Genetic counselling and DNA testing should be offered to all women following the diagnosis of an inherited cardiomyopathy.

  3. Peripartum cardiomyopathy.

    PubMed

    Sundin, Courtney Stanley

    2014-01-01

    Peripartum cardiomyopathy is a very rare, but serious life-threatening emergency. Early recognition of signs and symptoms, along with radiologic imaging and blood work, can facilitate timely diagnosis. Once peripartum cardiomyopathy is diagnosed, a multidisciplinary team can facilitate the delivery of quality care to promote optimal outcomes.

  4. Rigid spine syndrome and fatal cardiomyopathy.

    PubMed Central

    Colver, A F; Steer, C R; Godman, M J; Uttley, W S

    1981-01-01

    A 7 1/2-year-old girl had the clinical features of the rigid spine syndrome of Dubowitz. Muscle biopsy showed a predominance of type 2 fibres with neither myopathic features nor an increase in connective tissue. In addition, she had a hypertrophic cardiomyopathy with which she presented in heart failure and from which she died suddenly one month later. The association of rigid spine syndrome with cardiomyopathy has not been reported previously. Images Fig. 1 Fig. 2 Fig. 3 PMID:7193439

  5. The genetics of dilated cardiomyopathy

    PubMed Central

    Dellefave, Lisa; McNally, Elizabeth M.

    2010-01-01

    Purpose of review More than forty different individual genes have been implicated in the inheritance of dilated cardiomyopathy. For a subset of these genes, mutations can lead to a spectrum of cardiomyopathy that extends to hypertrophic cardiomyopathy and left ventricular noncompaction. In nearly all cases, there is an increased risk of arrhythmias. With some genetic mutations, extracardiac manifestations are likely to be present. The precise genetic etiology can usually not be discerned from the cardiac and/or extracardiac manifestations and requires molecular genetic diagnosis for prognostic determination and cardiac care. Recent findings Newer technologies are influencing genetic testing, especially cardiomyopathy genetic testing, where an increased number of genes are now routinely being tested simultaneously. While this approach to testing multiple genes is increasing the diagnostic yield, the analysis of multiple genes in one test is also resulting in a large amount of genetic information of unclear significance. Summary Genetic testing is highly useful in the care of patients and families, since it guides diagnosis, influences care and aids in prognosis. However, the large amount of benign human genetic variation may complicate genetic results, and often requires a skilled team to accurately interpret the findings. PMID:20186049

  6. Inflammatory dilated cardiomyopathy (DCMI).

    PubMed

    Maisch, Bernhard; Richter, Anette; Sandmöller, Andrea; Portig, Irene; Pankuweit, Sabine

    2005-09-01

    Cardiomyopathies are heart muscle diseases, which have been defined by their central hemodynamics and macropathology and divided in five major forms: dilated (DCM), hypertrophic (HCM), restrictive (RCM), right ventricular (RVCM), and nonclassifiable cardiomyopathies (NCCM). Furthermore, the most recent WHO/WHF definition also comprises, among the specific cardiomyopathies, inflammatory cardiomyopathy as a distinct entity, defined as myocarditis in association with cardiac dysfunction. Idiopathic, autoimmune, and infectious forms of inflammatory cardiomyopathy were recognized. Viral cardiomyopathy has been defined as viral persistence in a dilated heart. It may be accompanied by myocardial inflammation and then termed inflammatory viral cardiomyopathy (or viral myocarditis with cardiomegaly). If no inflammation is observed in the biopsy of a dilated heart (< 14 lymphocytes and macrophages/mm(2)), the term viral cardiomyopathy or viral persistence in DCM should be applied according to the WHF Task Force recommendations. Within the German heart failure net it is the authors' working hypothesis, that DCM shares genetic risk factors with other diseases of presumed autoimmune etiology and, therefore, the same multiple genes in combination with environmental factors lead to numerous different autoimmune diseases including DCM. Therefore, the authors' primary goal is to acquire epidemiologic data of patients with DCM regarding an infectious and inflammatory etiology of the disease. Circumstantial evidence points to a major role of viral myocarditis in the etiology of DCM. The common presence of viral genetic material in the myocardium of patients with DCM provides the most compelling evidence, but proof of causality is still lacking. In addition, autoimmune reactions have been described in many studies, indicating them as an important etiologic factor. Nevertheless, data on the proportion of patients, in whom both mechanisms play a role are still missing.A pivotal role for

  7. What's Cardiomyopathy

    MedlinePlus

    ... blood effectively and heart failure or irregular heartbeats (arrhythmias or dysrhythmia) may occur. Cardiomyopathy is classified as ... HCM are also at an increased risk of arrhythmias and sudden cardiac arrest. In advanced HCM (seen ...

  8. Dilated cardiomyopathy

    MedlinePlus

    ... Exposure to heavy metals such as lead, arsenic, cobalt, or mercury This condition can affect anyone at ... 25th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 60. Read More Anemia Arrhythmias Cardiomyopathy Fainting Headache Heart ...

  9. Familial cardiomyopathy in Norwegian Forest cats.

    PubMed

    März, Imke; Wilkie, Lois J; Harrington, Norelene; Payne, Jessie R; Muzzi, Ruthnea A L; Häggström, Jens; Smith, Ken; Luis Fuentes, Virginia

    2015-08-01

    Norwegian Forest cats (NFCs) are often listed as a breed predisposed to cardiomyopathy, but the characteristics of cardiomyopathy in this breed have not been described. The aim of this preliminary study was to report the features of NFC cardiomyopathy based on prospective echocardiographic screening of affected family groups; necropsy findings; and open-source breed screening databases. Prospective examination of 53 NFCs revealed no murmur or left ventricular (LV) outflow tract obstruction in any screened cat, though mild LV hypertrophy (defined as diastolic LV wall thickness ≥5.5mm) was present in 13/53 cats (25%). Gross pathology results and histopathological sections were analysed in eight NFCs, six of which had died of a cardiac cause. Myocyte hypertrophy, myofibre disarray and interstitial fibrosis typical of hypertrophic cardiomyopathy were present in 7/8 cats, but endomyocardial fibrosis suggestive of restrictive cardiomyopathy was also present in the same cats. Pedigree data analysis from 871 NFCs was supportive of a familial cardiomyopathy in this breed.

  10. [Peripartum cardiomyopathy].

    PubMed

    Mouquet, Frédéric; Bouabdallaoui, Nadia

    2015-01-01

    The peripartum cardiomyopathy is a rare form of dilated cardiomyopathy resulting from alteration of angiogenesis toward the end of pregnancy. The diagnosis is based on the association of clinical heart failure and systolic dysfunction assessed by echocardiography or magnetic resonance imaging. Diagnoses to rule out are myocardial infarction, amniotic liquid embolism, myocarditis, inherited cardiomyopathy, and history of treatment by anthracycline. Risk factors are advance maternal age (>30), multiparity, twin pregnancy, African origin, obesity, preeclampsia, gestational hypertension, and prolonged tocolytic therapy. Treatment of acute phase is identical to usual treatment of acute systolic heart failure. After delivery, VKA treatment should be discussed in case of systolic function <25% because of higher risk of thrombus. A specific treatment by bromocriptine can be initiated on a case-by-case basis. Complete recovery of systolic function is observed in 50% of cases. The mortality risk is low. Subsequent pregnancy should be discouraged, especially if systolic function did not recover.

  11. Primary prophylaxis of sudden death in hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, and dilated cardiomyopathy.

    PubMed

    Klein, George J; Krahn, Andrew D; Skanes, Allan C; Yee, Raymond; Gula, Lorne J

    2005-09-01

    We present an evidence-based overview of primary prevention of sudden cardiac death. Several recent studies have provided important data regarding pharmacologic and device-based therapy for patients with conditions that confer high risk for sudden death. A rational approach to these therapies, with emphasis on implanted cardiovertor defibrillators, is discussed.

  12. Cirrhotic cardiomyopathy.

    PubMed

    Ruiz-del-Árbol, Luis; Serradilla, Regina

    2015-11-07

    During the course of cirrhosis, there is a progressive deterioration of cardiac function manifested by the disappearance of the hyperdynamic circulation due to a failure in heart function with decreased cardiac output. This is due to a deterioration in inotropic and chronotropic function which takes place in parallel with a diastolic dysfunction and cardiac hypertrophy in the absence of other known cardiac disease. Other findings of this specific cardiomyopathy include impaired contractile responsiveness to stress stimuli and electrophysiological abnormalities with prolonged QT interval. The pathogenic mechanisms of cirrhotic cardiomyopathy include impairment of the b-adrenergic receptor signalling, abnormal cardiomyocyte membrane lipid composition and biophysical properties, ion channel defects and overactivity of humoral cardiodepressant factors. Cirrhotic cardiomyopathy may be difficult to determine due to the lack of a specific diagnosis test. However, an echocardiogram allows the detection of the diastolic dysfunction and the E/e' ratio may be used in the follow-up progression of the illness. Cirrhotic cardiomyopathy plays an important role in the pathogenesis of the impairment of effective arterial blood volume and correlates with the degree of liver failure. A clinical consequence of cardiac dysfunction is an inadequate cardiac response in the setting of vascular stress that may result in renal hypoperfusion leading to renal failure. The prognosis is difficult to establish but the severity of diastolic dysfunction may be a marker of mortality risk. Treatment is non-specific and liver transplantation may normalize the cardiac function.

  13. Restrictive cardiomyopathies.

    PubMed

    Nihoyannopoulos, Petros; Dawson, David

    2009-12-01

    Restrictive cardiomyopathies constitute a heterogenous group of heart muscle conditions that all have, in common, the symptoms of heart failure. Diastolic dysfunction with preserved systolic function is often the only echocardiographic abnormality that may be noted, although systolic dysfunction may also be an integral part of some specific pathologies, particularly in the most advanced cases such as amyloid infiltration of the heart. By far, the majority of restrictive cardiomyopathies are secondary to a systemic disorder such as amyloidosis, sarcoidosis, scleroderma, haemochromatosis, eosinophilic heart disease, or as a result of radiation treatment. The much more rare diagnosis of idiopathic restrictive cardiomyopathy is supported only by the absence of specific pathology on either endomyocardial biopsies or at post-mortem. Restrictive cardiomyopathy is diagnosed based on medical history, physical examination, and tests: such as blood tests, electrocardiogram, chest X-ray, echocardiography, and magnetic resonance imaging. With its wide availability, echocardiography is probably the most important investigation to identify the left ventricular dysfunction and should be performed early and by groups that are familiar with the wide variety of aetiologies. Finally, on rare occasions, the differential diagnosis from constrictive pericarditis may be necessary.

  14. [Hypertrophic miocardiopathy. An historical and anatomopathological review].

    PubMed

    Márquez, Manlio F; Ruíz-Siller, Teresita de Jesús; Méndez-Ramos, Rosario; Karabut, Erick; Aranda-Fraustro, Alberto; Jiménez-Becerra, Silvia

    Hypertrophic cardiomyopathy (HCM) is characterized by the presence of an abnormal hypertrophy of the left ventricle (LV), without dilation, and in the absence of any condition or another cardiac or systemic disease capable of inducing such hypertrophy. This primary or idiopathic hypertrophy can occur with or without dynamic obstruction (induced by exercise) of the LV outflow tract, so in its natural history two fundamental aspects are highlighted: the production of symptoms by blocking the LV outflow tract and the occurrence of sudden cardiac death secondary to ventricular arrhythmias. This revision includes the work of different Iberoamerican investigators, who contributed in an important way to lay the groundwork of what we know nowadays as HCM. It also includes the main anatomopathological characteristics, from its initial description to the new perspective we have concerning the myofiber disarray as the main histopathologic feature.

  15. What Is Cardiomyopathy?

    MedlinePlus

    ... page from the NHLBI on Twitter. What Is Cardiomyopathy? Cardiomyopathy refers to diseases of the heart muscle. These ... many causes, signs and symptoms, and treatments. In cardiomyopathy, the heart muscle becomes enlarged, thick, or rigid. ...

  16. Mitogenic cardiomyopathy: a lethal neonatal familial dilated cardiomyopathy characterized by myocyte hyperplasia and proliferation.

    PubMed

    Chang, Kenneth T E; Taylor, Glenn P; Meschino, Wendy S; Kantor, Paul F; Cutz, Ernest

    2010-07-01

    Pediatric cardiomyopathies are a heterogenous group of conditions of which dilated cardiomyopathies are the most common clinicomorphologic subtype. However, the etiology and pathogenesis of many cases of dilated cardiomyopathies remain unknown. We describe a series of 5 cases of a rare but clinically and histologically distinctive dilated cardiomyopathy that was uniformly lethal in early infancy. The 5 cases include 2 pairs of siblings. There was parental consanguinity in 1 of the 2 pairs of siblings. Death occurred in early infancy (range, 22-67 days; mean, 42 days) after a short history of general lethargy, decreased feeding, respiratory distress, or cyanosis. There was no specific birth or early neonatal problems. Autopsy revealed congestive cardiac failure and enlarged, dilated hearts with ventricular dilatation more pronounced than atrial dilatation, and endocardial fibroelastosis. Histology showed prominent hypertrophic nuclear changes of cardiac myofibers and markedly increased myocyte mitotic activity including occasional atypical mitoses. Immunohistochemical staining for Mib1 showed a markedly increased proliferative index of 10% to 20%. Ancillary investigations, including molecular studies, did not reveal a primary cause for the cardiomyopathies. This distinctive dilated cardiomyopathy characterized by unusual histologic features of myocyte nuclear hypertrophy and marked mitotic activity is lethal in early infancy. Its occurrence in 2 pairs of siblings suggests familial inheritance. Although the underlying molecular pathogenesis remains to be elucidated, it is important to recognize this distinctive entity for purposes of genetic counseling.

  17. Metabolic imaging of patients with cardiomyopathy

    SciTech Connect

    Geltman, E.M. )

    1991-09-01

    The cardiomyopathies comprise a diverse group of illnesses that can be characterized functionally by several techniques. However, the delineation of derangements of regional perfusion and metabolism have been accomplished only relatively recently with positron emission tomography (PET). Regional myocardial accumulation and clearance of 11C-palmitate, the primary myocardial substrate under most conditions, demonstrate marked spatial heterogeneity when studied under fasting conditions or with glucose loading. PET with 11C-palmitate permits the noninvasive differentiation of patients with nonischemic from ischemic dilated cardiomyopathy, since patients with ischemic cardiomyopathy demonstrate large zones of intensely depressed accumulation of 11C-palmitate, probably reflecting prior infarction. Patients with hypertrophic cardiomyopathy and Duchenne's muscular dystrophy demonstrate relatively unique patterns of myocardial abnormalities of perfusion and metabolism. The availability of new tracers and techniques for the evaluation of myocardial metabolism (11C-acetate), perfusion (H2(15)O), and autonomic tone (11-C-hydroxyephedrine) should facilitate further understanding of the pathogenesis of the cardiomyopathies.

  18. Cardiomyopathies in Noonan syndrome and the other RASopathies

    PubMed Central

    Gelb, Bruce D.; Roberts, Amy E.; Tartaglia, Marco

    2015-01-01

    Noonan syndrome and related disorders (Noonan syndrome with multiple lentigines, Costello syndrome, cardiofaciocutaneous syndrome, Noonan syndrome with loose anagen hair, and other related traits) are autosomal dominant traits. Mutations causing these disorders alter proteins relevant for signaling through RAS. Thus, these traits are now collectively called the RASopathies. While the RASopathies have pleiomorphic features, this review will focus on the hypertrophic cardiomyopathy observed in varying percentages of all of these traits. In addition, inherited abnormalities in one pathway gene, RAF1, cause pediatric-onset dilated cardiomyopathy. The pathogeneses for the RASopathy-associated cardiomyopathies are being elucidated, principally using animal models, leading to genotype-specific insights into how signal transduction is perturbed. Based on those findings, small molecule therapies seem possible for RASopathy-associated cardiomyopathies. PMID:26380542

  19. Development of Dilated Cardiomyopathy and Impaired Calcium Homeostasis with Cardiac-Specific Deletion of ESRRβ.

    PubMed

    Rowe, Glenn C; Asimaki, Angeliki; Graham, Evan L; Martin, Kimberly D; Margulies, Kenneth B; Das, Saumya; Saffitz, Jeffrey E; Arany, Zoltan

    2017-01-27

    Mechanisms underlying the development of Idiopathic Dilated Cardiomyopathy (DCM) remain poorly understood. Using transcription factor expression profiling, we identified estrogen-related receptor beta (ESRRβ), a member of the nuclear receptor family of transcription factors, as highly expressed in murine hearts and other highly oxidative striated muscle beds. Mice bearing cardiac-specific deletion of ESRRβ (MHC-ERRB KO) develop dilated cardiomyopathy and sudden death at approximately 10 months of age. Isolated adult cardiomyocytes from the MHC-ERRB KO mice showed an increase in calcium sensitivity and impaired cardiomyocyte contractility, which preceded echocardiographic cardiac remodeling and dysfunction by several months. Histological analyses of myocardial biopsies from patients with various cardiomyopathies revealed that ESRRβ protein is absent from the nucleus of cardiomyocytes from patients with DCM, but not other forms of cardiomyopathy (ischemic, hypertrophic and arrhythmogenic right ventricular cardiomyopathy). Taken together these observations suggest that ESRRβ is a critical component in the onset of dilated cardiomyopathy by affecting contractility and calcium balance.

  20. Magnetic Resonance Imaging of Non-ischemic Cardiomyopathies: A Pictorial Essay.

    PubMed

    Olivas-Chacon, Cristina I; Mullins, Carola; Stewart, Kevan; Akle, Nassim; Calleros, Jesus E; Ramos-Duran, Luis R

    2015-01-01

    Non-ischemic cardiomyopathies are defined as either primary or secondary diseases of the myocardium resulting in cardiac dysfunction. While primary cardiomyopathies are confined to the heart and can be genetic or acquired, secondary cardiomyopathies show involvement of the heart as a manifestation of an underlying systemic disease including metabolic, inflammatory, granulomatous, infectious, or autoimmune entities. Non-ischemic cardiomyopathies are currently classified as hypertrophic, dilated, restrictive, or unclassifiable, including left ventricular non-compaction. Cardiovascular Magnetic Resonance Imaging (CMRI) not only has the capability to assess cardiac morphology and function, but also the ability to detect edema, hemorrhage, fibrosis, and intramyocardial deposits, providing a valuable imaging tool in the characterization of non-ischemic cardiomyopathies. This pictorial essay shows some of the most important non-ischemic cardiomyopathies with an emphasis on magnetic resonance imaging features.

  1. Magnetic Resonance Imaging of Non-ischemic Cardiomyopathies: A Pictorial Essay

    PubMed Central

    Olivas-Chacon, Cristina I; Mullins, Carola; Stewart, Kevan; Akle, Nassim; Calleros, Jesus E; Ramos-Duran, Luis R

    2015-01-01

    Non-ischemic cardiomyopathies are defined as either primary or secondary diseases of the myocardium resulting in cardiac dysfunction. While primary cardiomyopathies are confined to the heart and can be genetic or acquired, secondary cardiomyopathies show involvement of the heart as a manifestation of an underlying systemic disease including metabolic, inflammatory, granulomatous, infectious, or autoimmune entities. Non-ischemic cardiomyopathies are currently classified as hypertrophic, dilated, restrictive, or unclassifiable, including left ventricular non-compaction. Cardiovascular Magnetic Resonance Imaging (CMRI) not only has the capability to assess cardiac morphology and function, but also the ability to detect edema, hemorrhage, fibrosis, and intramyocardial deposits, providing a valuable imaging tool in the characterization of non-ischemic cardiomyopathies. This pictorial essay shows some of the most important non-ischemic cardiomyopathies with an emphasis on magnetic resonance imaging features. PMID:26199786

  2. Reversible Cardiomyopathies

    PubMed Central

    Patel, Harsh; Madanieh, Raef; Kosmas, Constantine E; Vatti, Satya K; Vittorio, Timothy J

    2015-01-01

    Cardiomyopathies (CMs) have many etiological factors that can result in severe structural and functional dysregulation. Fortunately, there are several potentially reversible CMs that are known to improve when the root etiological factor is addressed. In this article, we discuss several of these reversible CMs, including tachycardia-induced, peripartum, inflammatory, hyperthyroidism, Takotsubo, and chronic illness–induced CMs. Our discussion also includes a review on their respective pathophysiology, as well as possible management solutions. PMID:26052233

  3. [Cardiomyopathies. I: classification of cardiomyopathies--dilated cardiomyopathy].

    PubMed

    Schultheiss, H P; Noutsias, M; Kühl, U; Lassner, D; Gross, U; Poller, W; Pauschinger, M

    2005-11-01

    Cardiomyopathies are common causes of heart failure and sudden cardiac death. According to the WHO classification, "specific" cardiomyopathies are differentiated from "idiopathic" cardiomyopathies. Thus, this classification is primarily based on pathophysiological characteristics. The diagnostic spectrum in cardiomyopathies comprises the entire spectrum of non-invasive and invasive cardiological examination techniques. The exact verification of certain cardiomyopathies necessitates additionally investigations. For example, immunohistological and molecular biological investigations of endomyocardial biopsies may confirm inflammatory cardiomyopathy, which is often induced by viruses. Several studies have shown that specific immunomodulatory treatment options can halt the progressive course of the disease. Several gene mutations have been identified in genetic/familial dilated cardiomyopathy. First-degree relatives should be screened for early stages. Primary prevention of sudden cardiac death shows increasing superiority of the implantable defibrillator compared with pharmacological approaches (i.e. amiodarone).

  4. Genetic advances in sarcomeric cardiomyopathies: state of the art.

    PubMed

    Ho, Carolyn Y; Charron, Philippe; Richard, Pascale; Girolami, Francesca; Van Spaendonck-Zwarts, Karin Y; Pinto, Yigal

    2015-04-01

    Genetic studies in the 1980s and 1990s led to landmark discoveries that sarcomere mutations cause both hypertrophic and dilated cardiomyopathies. Sarcomere mutations also likely play a role in more complex phenotypes and overlap cardiomyopathies with features of hypertrophy, dilation, diastolic abnormalities, and non-compaction. Identification of the genetic cause of these important conditions provides unique opportunities to interrogate and characterize disease pathogenesis and pathophysiology, starting from the molecular level and expanding from there. With such insights, there is potential for clinical translation that may transform management of patients and families with inherited cardiomyopathies. If key pathways for disease development can be identified, they could potentially serve as targets for novel disease-modifying or disease-preventing therapies. By utilizing gene-based diagnostic testing, we can identify at-risk individuals prior to the onset of clinical disease, allowing for disease-modifying therapy to be initiated early in life, at a time that such treatment may be most successful. In this section, we review the current application of genetics in clinical management, focusing on hypertrophic cardiomyopathy as a paradigm; discuss state-of-the-art genetic testing technology; review emerging knowledge of gene expression in sarcomeric cardiomyopathies; and discuss both the prospects, as well as the challenges, of bringing genetics to medicine.

  5. [Cardiomyopathies and pregnancy--how often, when to decide to terminate?].

    PubMed

    Nowalany-Kozielska, Ewa

    2015-01-01

    Cardiomyopathies are a small percentage of heart disease in pregnant women, but usually cause severe complications. It is not know the exact incidence of cardiomyopathy associated with pregnancy in Europe. In these patients, there is a higher probability of death due to changes in hemodynamic, metabolic and hemostatic that occur in pregnancy. Pregnant mortality is 2.4% vs. 0.007%--in the normal population. The most common cause of severe maternal complications is peripartum cardiomyopathy (PPCM). In dilated cardiomyopathy (DCM) and restrictive (RCM) is usually observed significant clinical deterioration during pregnancy. On the other hand, in patients with hypertrophic cardiomyopathy (HCM), pregnancy and childbirth are often associated with a low risk of complications. There is a greater risk in women presenting symptoms before and on pregnancy and in women with large inrtaventricular and subaortic pressure gradient. There are only a few case reports of pregnancy in patients with rare storage diseases and infiltrative phenotype of hypertrophic cardiomyopathy. For these patients the pregnancy is contraindicated. In patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) is sometimes the severity of arrhythmia in the third trimester of pregnancy, and childbirth (natural or cesarean section) is usually safe. Remember to informing women with various cardiomyopathies both the risks of pregnancy and about the possibility of transferring the disease to offspring. Contraception should be advised in many cases.

  6. Targets for therapy in sarcomeric cardiomyopathies.

    PubMed

    Tardiff, Jil C; Carrier, Lucie; Bers, Donald M; Poggesi, Corrado; Ferrantini, Cecilia; Coppini, Raffaele; Maier, Lars S; Ashrafian, Houman; Huke, Sabine; van der Velden, Jolanda

    2015-04-01

    To date, no compounds or interventions exist that treat or prevent sarcomeric cardiomyopathies. Established therapies currently improve the outcome, but novel therapies may be able to more fundamentally affect the disease process and course. Investigations of the pathomechanisms are generating molecular insights that can be useful for the design of novel specific drugs suitable for clinical use. As perturbations in the heart are stage-specific, proper timing of drug treatment is essential to prevent initiation and progression of cardiac disease in mutation carrier individuals. In this review, we emphasize potential novel therapies which may prevent, delay, or even reverse hypertrophic cardiomyopathy caused by sarcomeric gene mutations. These include corrections of genetic defects, altered sarcomere function, perturbations in intracellular ion homeostasis, and impaired myocardial energetics.

  7. Targets for therapy in sarcomeric cardiomyopathies

    PubMed Central

    Tardiff, Jil C.; Carrier, Lucie; Bers, Donald M.; Poggesi, Corrado; Ferrantini, Cecilia; Coppini, Raffaele; Maier, Lars S.; Ashrafian, Houman; Huke, Sabine; van der Velden, Jolanda

    2015-01-01

    To date, no compounds or interventions exist that treat or prevent sarcomeric cardiomyopathies. Established therapies currently improve the outcome, but novel therapies may be able to more fundamentally affect the disease process and course. Investigations of the pathomechanisms are generating molecular insights that can be useful for the design of novel specific drugs suitable for clinical use. As perturbations in the heart are stage-specific, proper timing of drug treatment is essential to prevent initiation and progression of cardiac disease in mutation carrier individuals. In this review, we emphasize potential novel therapies which may prevent, delay, or even reverse hypertrophic cardiomyopathy caused by sarcomeric gene mutations. These include corrections of genetic defects, altered sarcomere function, perturbations in intracellular ion homeostasis, and impaired myocardial energetics. PMID:25634554

  8. X-linked cardiomyopathy is heterogeneous

    SciTech Connect

    Wilson, M.J.; Sillence, D.O.; Mulley, J.C.

    1994-09-01

    Two major loci of X-linked cardiomyopathy have been mapped by linkage analysis. The gene for X-linked dilated cardiomyopathy (XLCM) is mapped to the dystrophin locus at Xp21, while Barth syndrome has been localised to distal Xq28. XLCM usually presents in juvenile males with no skeletal disease but decreased dystrophin in cardiac muscle. Barth syndrome most often presents in infants and is characterized by skeletal myopathy, short stature and neutropenia in association with cardiomyopathy of variable severity. Prior to carrier or prenatal diagnosis in a family, delineation of the cardiomyopathy locus involved is essential. We report the linkage mapping of a large kindred in which several male infants have died with hypertrophic cardiomyopathy. There is a family history of unexplained death of infant males less than 6 months old over 4 generations. Features of Barth syndrome such as short stature, skeletal myopathy and neutropenia have not been observed. Genotyping at 10 marker loci in Xq28 has revealed significant pairwise lod scores with the cardiomyopathy phenotype at DXS52 (Z=2.21 at {theta}=0.0), at markers p26 and p39 near DXS15 (Z=2.30 at {theta}=0.0) and at F8C (Z=2.24 at {theta}=0.0). A recombinant detected with DXS296 defines the proximal limit to the localization. No recombinants were detected at any of the loci distal to DXS296. The most distal marker in Xq28, DXS1108, is within 500 kb of the telomere. As the gene in this family is localized to Xq28, it is possible that this disorder is an allelic variant at the Barth syndrome locus.

  9. Ubiquitin-proteasome system and hereditary cardiomyopathies.

    PubMed

    Schlossarek, Saskia; Frey, Norbert; Carrier, Lucie

    2014-06-01

    Adequate protein turnover is essential for cardiac homeostasis. Different protein quality controls are involved in the maintenance of protein homeostasis, including molecular chaperones and co-chaperones, the autophagy-lysosomal pathway, and the ubiquitin-proteasome system (UPS). In the last decade, a series of evidence has underlined a major function of the UPS in cardiac physiology and disease. Particularly, recent studies have shown that dysfunctional proteasomal function leads to cardiac disorders. Hypertrophic and dilated cardiomyopathies are the two most prevalent inherited cardiomyopathies. Both are primarily transmitted as an autosomal-dominant trait and mainly caused by mutations in genes encoding components of the cardiac sarcomere, including a relevant striated muscle-specific E3 ubiquitin ligase. A growing body of evidence indicates impairment of the UPS in inherited cardiomyopathies as determined by measurement of the level of ubiquitinated proteins, the activities of the proteasome and/or the use of fluorescent UPS reporter substrates. The present review will propose mechanisms of UPS impairment in inherited cardiomyopathies, summarize the potential consequences of UPS impairment, including activation of the unfolded protein response, and underline some therapeutic options available to restore proteasome function and therefore cardiac homeostasis and function. This article is part of a Special Issue entitled "Protein Quality Control, the Ubiquitin Proteasome System, and Autophagy".

  10. Arrhythmogenic cardiomyopathy.

    PubMed

    Pilichou, Kalliopi; Thiene, Gaetano; Bauce, Barbara; Rigato, Ilaria; Lazzarini, Elisabetta; Migliore, Federico; Perazzolo Marra, Martina; Rizzo, Stefania; Zorzi, Alessandro; Daliento, Luciano; Corrado, Domenico; Basso, Cristina

    2016-04-02

    Arrhythmogenic cardiomyopathy (AC) is a heart muscle disease clinically characterized by life-threatening ventricular arrhythmias and pathologically by an acquired and progressive dystrophy of the ventricular myocardium with fibro-fatty replacement. Due to an estimated prevalence of 1:2000-1:5000, AC is listed among rare diseases. A familial background consistent with an autosomal-dominant trait of inheritance is present in most of AC patients; recessive variants have also been reported, either or not associated with palmoplantar keratoderma and woolly hair. AC-causing genes mostly encode major components of the cardiac desmosome and up to 50% of AC probands harbor mutations in one of them. Mutations in non-desmosomal genes have been also described in a minority of AC patients, predisposing to the same or an overlapping disease phenotype. Compound/digenic heterozygosity was identified in up to 25% of AC-causing desmosomal gene mutation carriers, in part explaining the phenotypic variability. Abnormal trafficking of intercellular proteins to the intercalated discs of cardiomyocytes and Wnt/beta catenin and Hippo signaling pathways have been implicated in disease pathogenesis.AC is a major cause of sudden death in the young and in athletes. The clinical picture may include a sub-clinical phase; an overt electrical disorder; and right ventricular or biventricular pump failure. Ventricular fibrillation can occur at any stage. Genotype-phenotype correlation studies led to identify biventricular and dominant left ventricular variants, thus supporting the use of the broader term AC.Since there is no "gold standard" to reach the diagnosis of AC, multiple categories of diagnostic information have been combined and the criteria recently updated, to improve diagnostic sensitivity while maintaining specificity. Among diagnostic tools, contrast enhanced cardiac magnetic resonance is playing a major role in detecting left dominant forms of AC, even preceding morpho

  11. Severe biventricular hypertrophy mimicking infiltrative cardiomyopathy in old man with pulmonary stenosis and systemic hypertension.

    PubMed

    Efe, Süleyman Çağan; Kahveci, Gokhan; Bakal, Ruken Bengi; Akpinar, Suzan Hatipoğlu; Unkun, Tuba; Ozdemir, Nihal

    2015-01-01

    Hypertrophic biventricular cardiomyopathy is a rare finding and generally caused by systemic infiltrative diseases. Its association with pulmonary stenosis in same patient is even rarer. We report a case report of male patient with biventricular hypertrophy coexisting with pulmonary valve stenosis and systemic hypertension.

  12. [Septal alcohol ablation in patients with hypertrophic cardiomyopathy].

    PubMed

    López-Aburto, Gustavo; Palacios-Rodríguez, Juan Manuel; Cantú-Ramírez, Samuel; Galván-García, Eduardo; Tolosa-Dzul, Gonzalo; Morán-Benavente, Armando; Ontiveros-Martínez, Raúl

    2013-01-01

    Objetivo: conocer características demográficas, clínicas y hemodinámicas de los pacientes con ablación con alcohol para tratar la miocardiopatía hipertrófica septal obstructiva (MHSO). Métodos: estudio observacional, longitudinal, descriptivo de 21 pacientes con MHSO resistente a tratamiento o con gradiente = 30 mm Hg en reposo o = 60 mm Hg provocado y con movimiento sistólico anterior o insuficiencia mitral > grado II. Resultados: edad de 50 ± 16 años; hombres 38.1 % y mujeres 61.9 %. Los síntomas fueron angor 42.9 %, disnea 85.7 % y síncope 23.8 %. La clase funcional NYHA preablación fue grados III y IV en 61.9 %; al año todos tenían grados I y II. Preablación y al año, el espesor del septo interventricular fue de 22.7 ± 4.9 y 20.7 ± 3.1 mm. Preablación, después y al año, la fracción de eyección fue de 65.5 ± 7, 62.2 ± 6.5 y 68.7 ± 6.2 %. Preablación, después y al año, el gradiente del tracto de salida del ventrículo izquierdo fue de 106.9 ± 29.9, 44.6 ± 24.3 y 22.0 ± 5.7 mm Hg. Preablación, la insuficiencia mitral fue grados III y IV en 33.3 y 47.6 % y al año fue grados 0 en 52.4 %, I en 28.6 % y II en 19 %. No hubo defunciones intrahospitalarias. Conclusiones: la ablación septal con alcohol en pacientes con MHSO fue exitosa.

  13. Passive microlesion detection and mapping for treatment of hypertrophic cardiomyopathy

    NASA Astrophysics Data System (ADS)

    Zhu, Yiying I.; Miller, Douglas L.; Dou, Chunyan; Kripfgans, Oliver D.

    2017-03-01

    Intermittent high intensity ultrasound pulses with circulating contrast agent microbubbles can induce scattered microlesions of potential value for myocardial reduction therapy. This paper presents an in vitro setup imitating the treatment for monitoring development. A preclinical imaging system with a single element transducer, synchronization and receive-only imaging transducer array has been implemented on a research platform. Contrast agent microbubbles pumped in a dialysis tubing setup were exposed to high intensity focused ultrasound at 1.0/3.5 MHz center frequencies. Polystyrene spheres were employed as linear scatterers compared to contrast agents for system transfer function equalization. A cavitation mapping technique was employed to spatially locate and depict microbubble activity during treatment. For high acoustic pressure amplitudes a 5 dB difference between contrast agent and solid spheres was observed and spatially mapped. The in-plane resolution was 4.5 mm for axial and 1.5 mm laterally. In the future, this cavitation detection scheme will be applied to monitor in vivo microlesioning in real-time.

  14. Genetic diagnostics and genetic counselling in Hypertrophic Cardiomyopathy (HCM)

    PubMed Central

    2010-01-01

    Dutch professional groups involved in drawing up this guideline: cardiologists, paediatric cardiologists, clinical geneticists, clinical molecular geneticists, genetic counsellors, psychosocial workers, associated with or cooperating with the university hospitals’ outpatient clinics for cardiogenetics. Approved by the NVVC, VKGN and NVK (paediatric cardiology section). NVVC - Nederlandse Vereniging voor Cardiologie – Dutch Society for Cardiology; VKGN - Vereniging Klinische Genetica Nederland – the Netherlands Society for Clinical Genetics; NVK - Nederlandse Vereniging Kindergeneeskunde – Dutch Society for Paediatrics. First published in Dutch in June 2009. PMID:20390065

  15. Analysis of shape and motion of the mitral annulus in subjects with and without cardiomyopathy by echocardiographic 3-dimensional reconstruction

    NASA Technical Reports Server (NTRS)

    Flachskampf, F. A.; Chandra, S.; Gaddipatti, A.; Levine, R. A.; Weyman, A. E.; Ameling, W.; Hanrath, P.; Thomas, J. D.

    2000-01-01

    The shape and dynamics of the mitral annulus of 10 patients without heart disease (controls), 3 patients with dilated cardiomyopathy, and 5 patients with hypertrophic obstructive cardiomyopathy and normal systolic function were analyzed by transesophageal echocardiography and 3-dimensional reconstruction. Mitral annular orifice area, apico-basal motion of the annulus, and nonplanarity were calculated over time. Annular area was largest in end diastole and smallest in end systole. Mean areas were 11.8 +/- 2.5 cm(2) (controls), 15.2 +/- 4.2 cm(2) (dilated cardiomyopathy), and 10.2 +/- 2.4 cm(2) (hypertrophic cardiomyopathy) (P = not significant). After correction for body surface, annuli from patients with normal left ventricular function were smaller than annuli from patients with dilated cardiomyopathy (5.9 +/- 1.2 cm(2)/m(2) vs 7.7 +/- 1.0 cm(2)/m(2); P <.02). The change in area during the cardiac cycle showed significant differences: 23.8% +/- 5.1% (controls), 13.2% +/- 2.3% (dilated cardiomyopathy), and 32.4% +/- 7.6% (hypertrophic cardiomyopathy) (P <.001). Apico-basal motion was highest in controls, followed by those with hypertrophic obstructive and dilated cardiomyopathy (1.0 +/- 0.3 cm, 0.8 +/- 0.2 cm, 0.3 +/- 0.2 cm, respectively; P <.01). Visual inspection and Fourier analysis showed a consistent pattern of anteroseptal and posterolateral elevations of the annulus toward the left atrium. In conclusion, although area changes and apico-basal motion of the mitral annulus strongly depend on left ventricular systolic function, nonplanarity is a structural feature preserved throughout the cardiac cycle in all three groups.

  16. Diagnosis and management of inherited cardiomyopathies.

    PubMed

    Millar, Lynne; Sharma, Sanjay

    2014-10-01

    Inherited heart conditions are the most common cause of sudden cardiac death in those under the age of 35 and the leading cause of non-traumatic death in young athletes. Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease affecting 1 in 500 of the population. Some patients may exhibit severe left ventricular hypertrophy, others may show nothing more than an abnormal ECG. Left ventricular hypertrophy most commonly manifests in the second decade of life. Sudden death is rare and usually affects patients in the first three decades whereas older patients present with heart failure, atrial fibrillation and stroke. Arrhythmogenic right ventricular cardiomyopathy is a rare, autosomal dominant heart muscle disorder which affects between 1 in 1,000 and 1 in 5,000 of the population. Dilated cardiomyopathy (DCM) is characterised by a dilated left ventricle with impaired function that cannot be explained by ischaemic heart disease, hypertension or valvular heart disease. At least 25% of cases of DCM are familial. DCM may be associated with multisystem conditions such as muscular dystrophy. Chemotherapy and certain other drugs, alcohol abuse and myocarditis may also lead to a dilated and poorly contracting left ventricle. In many cases the first manifestation of an inherited cardiomyopathy can be a sudden cardiac arrest. Other presentations include chest pain or breathlessness during exertion, palpitations and syncope. In many of the cardiomyopathies, the diagnosis can be made with a standard ECG and echocardiogram. However if the diagnosis is not certain or the cardiologist wishes to look at the heart structure in greater detail, a cardiac MRI may be performed.

  17. Dilated cardiomyopathy.

    PubMed

    Weintraub, Robert G; Semsarian, Christopher; Macdonald, Peter

    2017-02-09

    Dilated cardiomyopathy is defined by the presence of left ventricular dilatation and contractile dysfunction. Genetic mutations involving genes that encode cytoskeletal, sarcomere, and nuclear envelope proteins, among others, account for up to 35% of cases. Acquired causes include myocarditis and exposure to alcohol, drugs and toxins, and metabolic and endocrine disturbances. The most common presenting symptoms relate to congestive heart failure, but can also include circulatory collapse, arrhythmias, and thromboembolic events. Secondary neurohormonal changes contribute to reverse remodelling and ongoing myocyte damage. The prognosis is worst for individuals with the lowest ejection fractions or severe diastolic dysfunction. Treatment of chronic heart failure comprises medications that improve survival and reduce hospital admission-namely, angiotensin converting enzyme inhibitors and β blockers. Other interventions include enrolment in a multidisciplinary heart failure service, and device therapy for arrhythmia management and sudden death prevention. Patients who are refractory to medical therapy might benefit from mechanical circulatory support and heart transplantation. Treatment of preclinical disease and the potential role of stem-cell therapy are being investigated.

  18. Anthracycline cardiomyopathy.

    PubMed

    Kobrinsky, N L; Ramsay, N K; Krivit, W

    1982-01-01

    Life-threatening irreversible cardiomyopathy is a major complication of anthracycline therapy, particularly in the pediatric population. The pediatric cardiologist, in concert with the primary oncologist, should therefore play a major role in the care of patients receiving these agents and in clinical trials involving their use. Many risk factors and their relationships to drug pharmacokinetics, mechanisms of action, and toxicity have been identified. These data provide a rational basis for present-day recommendations regarding anthracycline administration and dosage scheduling. They furthermore provide potential avenues for clinical investigation aimed at improving the therapeutic index of these agents: alpha-tocopherol, cytochrome Q10, and other free radical scavengers may decrease the deleterious effects of free radical generation on the myocardium without apparent interference with tumoricidal effect. The cardiac glycosides may decrease cardiac toxicity by specific myocardial exclusion. Anthracycline analogs have been designed to specifically inhibit myocardial binding and/or free radical generation. Clinical trials involving these agents are difficult to interpret because of variability in front end risk factors and dosage schedules in the study population. Furthermore, the relatively low (5 to 10%) incidence of affected patients implies the need for large numbers to demonstrate a statistically significant benefit. Pediatric protocols addressing these issues are urgently needed. Guidelines for present-day management and future studies are outlined.

  19. Neonatal dilated cardiomyopathy.

    PubMed

    Soares, Paulo; Rocha, Gustavo; Pissarra, Susana; Soares, Henrique; Flôr-de-Lima, Filipa; Costa, Sandra; Moura, Cláudia; Dória, Sofia; Guimarães, Hercília

    2017-03-01

    Cardiomyopathies are rare diseases of the heart muscle, of multiple causes, that manifest with various structural and functional phenotypes but are invariably associated with cardiac dysfunction. Dilated cardiomyopathy is the commonest cardiomyopathy in children, and the majority present before one year of age. Its etiology may be acquired or genetic. Myocarditis is an important cause and is responsible for the majority of acquired cases. Inherited (familial) forms of dilated cardiomyopathy may occur in 25-50% of patients. Echocardiographic and tissue Doppler studies are the basis for diagnosis of dilated cardiomyopathy in most patients. Marked dilatation of the left ventricle with global hypokinesis is the hallmark of the disease. This review will cover the classification, epidemiology and management of newborns with dilated cardiomyopathy. In particular, a comprehensive and up-to-date review of the genetic study of dilated cardiomyopathy and of detailed echocardiographic assessment of these patients will be presented.

  20. Genetic mutations and mechanisms in dilated cardiomyopathy.

    PubMed

    McNally, Elizabeth M; Golbus, Jessica R; Puckelwartz, Megan J

    2013-01-01

    Genetic mutations account for a significant percentage of cardiomyopathies, which are a leading cause of congestive heart failure. In hypertrophic cardiomyopathy (HCM), cardiac output is limited by the thickened myocardium through impaired filling and outflow. Mutations in the genes encoding the thick filament components myosin heavy chain and myosin binding protein C (MYH7 and MYBPC3) together explain 75% of inherited HCMs, leading to the observation that HCM is a disease of the sarcomere. Many mutations are "private" or rare variants, often unique to families. In contrast, dilated cardiomyopathy (DCM) is far more genetically heterogeneous, with mutations in genes encoding cytoskeletal, nucleoskeletal, mitochondrial, and calcium-handling proteins. DCM is characterized by enlarged ventricular dimensions and impaired systolic and diastolic function. Private mutations account for most DCMs, with few hotspots or recurring mutations. More than 50 single genes are linked to inherited DCM, including many genes that also link to HCM. Relatively few clinical clues guide the diagnosis of inherited DCM, but emerging evidence supports the use of genetic testing to identify those patients at risk for faster disease progression, congestive heart failure, and arrhythmia.

  1. Update on hypertrophic scar treatment

    PubMed Central

    Rabello, Felipe Bettini; Souza, Cleyton Dias; Júnior, Jayme Adriano Farina

    2014-01-01

    Scar formation is a consequence of the wound healing process that occurs when body tissues are damaged by a physical injury. Hypertrophic scars and keloids are pathological scars resulting from abnormal responses to trauma and can be itchy and painful, causing serious functional and cosmetic disability. The current review will focus on the definition of hypertrophic scars, distinguishing them from keloids and on the various methods for treating hypertrophic scarring that have been described in the literature, including treatments with clearly proven efficiency and therapies with doubtful benefits. Numerous methods have been described for the treatment of abnormal scars, but to date, the optimal treatment method has not been established. This review will explore the differences between different types of nonsurgical management of hypertrophic scars, focusing on the indications, uses, mechanisms of action, associations and efficacies of the following therapies: silicone, pressure garments, onion extract, intralesional corticoid injections and bleomycin. PMID:25141117

  2. Inherited cardiomyopathies: molecular genetics and clinical genetic testing in the postgenomic era.

    PubMed

    Teekakirikul, Polakit; Kelly, Melissa A; Rehm, Heidi L; Lakdawala, Neal K; Funke, Birgit H

    2013-03-01

    Inherited cardiomyopathies include hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, left ventricular noncompaction, and restrictive cardiomyopathy. These diseases have a substantial genetic component and predispose to sudden cardiac death, which provides a high incentive to identify and sequence disease genes in affected individuals to identify pathogenic variants. Clinical genetic testing, which is now widely available, can be a powerful tool for identifying presymptomatic individuals. However, locus and allelic heterogeneity are the rule, as are clinical variability and reduced penetrance of disease in carriers of pathogenic variants. These factors, combined with genetic and phenotypic overlap between different cardiomyopathies, have made clinical genetic testing a lengthy and costly process. Next-generation sequencing technologies have removed many limitations such that comprehensive testing is now feasible, shortening diagnostic odysseys for clinically complex cases. Remaining challenges include the incomplete understanding of the spectrum of benign and pathogenic variants in the cardiomyopathy genes, which is a source of inconclusive results. This review provides an overview of inherited cardiomyopathies with a focus on their genetic etiology and diagnostic testing in the postgenomic era.

  3. [Classification of cardiomyopathies according to the WHO/ISFC Task Force--more questions than answers?].

    PubMed

    Maisch, B

    1998-04-15

    The most recent WHO/ISFC classification of cardiomyopathies (1995) describes as cardiomyopathies all heart muscle diseases, which demonstrate a disturbance of cardiac function. It distinguishes primarily according to hemodynamic criteria the following 5 forms: 1. dilated (DCM), 2. hypertrophic (HCM), 3. restrictive (RCM) from 4. arrhythmogenic right ventricular (ARVCM) and assembles in 5. non-classified cardiomyopathies (NKCM) the non-classifiable forms. When compared to the 18-year-old former classification several points have been altered: 1. ARVCM has been introduced as a new entity. 2. The new term ischemic cardiomyopathy has been reserved for the remodeling process of the non-infarcted myocardium and does not mean hemodynamic alterations of an infarcted area (aneurysm), of stunned or hibernating myocardium. Hypertensive cardiomyopathy corresponds to left ventricular hypertrophy in hypertensive patients, valvular cardiomyopathy identifies cardiomegaly, which cannot sufficiently be explained by the valvular dysfunction (stenoses or insufficiency) alone. For the first time the term inflammatory cardiomyopathy has been used and defined as acute or chronic myocarditis associated with cardiac dysfunction, for which etiological and pathogenetic factors, e.g. viral or microbial infection or autoimmune processes have been made responsible. Two ISFC task forces have just recently clarified in consensus conferences the immunohistopathological criteria for chronic myocarditis or dilated cardiomyopathy with inflammation (DCMi: > 14 lymphocytes or macrophages/mm3) and set standards for molecular and virological diagnoses in endomyocardial biopsies.

  4. Human viral cardiomyopathy.

    PubMed

    Maisch, Bernhard; Ristic, Arsen D; Portig, Irene; Pankuweit, Sabine

    2003-01-01

    Viral infection of the heart is relatively common, usually asymptomatic and has a spontaneous and complete resolution. It can, however, in rare cases, lead to substantial cardiac damage, development of viral cardiomyopathy and congestive heart failure. Viral cardiomyopathy is defined as viral persistence in a dilated heart. It may be accompanied by myocardial inflammation and then termed inflammatory viral cardiomyopathy (or viral myocarditis with cardiomegaly). If no inflammation is observed in the biopsy of a dilated heart (<14 lymphocytes and macrophages/mm ) the term viral cardiomyopathy or viral persistence in dilated cardiomyopathy should be applied. The diagnosis of myocarditis and viral cardiomyopathy can be made only by endomyocardial biopsy, implementing the WHO/WHF criteria, and PCR techniques for identification of viral genome. The most frequent cardiotropic viruses detected by endomyocardial biopsy are Parvo B19, enteroviruses, adenoviruses, cytomegalovirus, and less frequently Epstein-Barr virus, and influenza virus.

  5. [Desmin-related cardiomyopathy].

    PubMed

    Rybakova, M G; Kuznetsova, I A; Gudkova, A Ia; Kostareva, A A; Semernin, E N

    2011-01-01

    The observation of 26 years old patient with desminopathy declared itself by hypertrophied cardiomyopathy with its transformation into restrictive phenotype is presented. The features of pathologic course at the patient were a dominance and diversity of cardiac manifestations. Endomyocardiac biopsy allowed suspecting the desminopathy confirmed by genetic analysis. Morphological features of desmin-related cardiomyopathy were irregular desmin conglomerates mainly located under sarcolemma and an indirect histological signs of idiopathic cardiomyopathy as well nuclear polymorphism, perinuclear "nimbus", chaotic located myofibrils.

  6. Mechanistic heterogeneity in contractile properties of α-tropomyosin (TPM1) mutants associated with inherited cardiomyopathies.

    PubMed

    Gupte, Tejas M; Haque, Farah; Gangadharan, Binnu; Sunitha, Margaret S; Mukherjee, Souhrid; Anandhan, Swetha; Rani, Deepa Selvi; Mukundan, Namita; Jambekar, Amruta; Thangaraj, Kumarasamy; Sowdhamini, Ramanathan; Sommese, Ruth F; Nag, Suman; Spudich, James A; Mercer, John A

    2015-03-13

    The most frequent known causes of primary cardiomyopathies are mutations in the genes encoding sarcomeric proteins. Among those are 30 single-residue mutations in TPM1, the gene encoding α-tropomyosin. We examined seven mutant tropomyosins, E62Q, D84N, I172T, L185R, S215L, D230N, and M281T, that were chosen based on their clinical severity and locations along the molecule. The goal of our study was to determine how the biochemical characteristics of each of these mutant proteins are altered, which in turn could provide a structural rationale for treatment of the cardiomyopathies they produce. Measurements of Ca(2+) sensitivity of human β-cardiac myosin ATPase activity are consistent with the hypothesis that hypertrophic cardiomyopathies are hypersensitive to Ca(2+) activation, and dilated cardiomyopathies are hyposensitive. We also report correlations between ATPase activity at maximum Ca(2+) concentrations and conformational changes in TnC measured using a fluorescent probe, which provide evidence that different substitutions perturb the structure of the regulatory complex in different ways. Moreover, we observed changes in protein stability and protein-protein interactions in these mutants. Our results suggest multiple mechanistic pathways to hypertrophic and dilated cardiomyopathies. Finally, we examined a computationally designed mutant, E181K, that is hypersensitive, confirming predictions derived from in silico structural analysis.

  7. Mechanistic Heterogeneity in Contractile Properties of α-Tropomyosin (TPM1) Mutants Associated with Inherited Cardiomyopathies*

    PubMed Central

    Gupte, Tejas M.; Haque, Farah; Gangadharan, Binnu; Sunitha, Margaret S.; Mukherjee, Souhrid; Anandhan, Swetha; Rani, Deepa Selvi; Mukundan, Namita; Jambekar, Amruta; Thangaraj, Kumarasamy; Sowdhamini, Ramanathan; Sommese, Ruth F.; Nag, Suman; Spudich, James A.; Mercer, John A.

    2015-01-01

    The most frequent known causes of primary cardiomyopathies are mutations in the genes encoding sarcomeric proteins. Among those are 30 single-residue mutations in TPM1, the gene encoding α-tropomyosin. We examined seven mutant tropomyosins, E62Q, D84N, I172T, L185R, S215L, D230N, and M281T, that were chosen based on their clinical severity and locations along the molecule. The goal of our study was to determine how the biochemical characteristics of each of these mutant proteins are altered, which in turn could provide a structural rationale for treatment of the cardiomyopathies they produce. Measurements of Ca2+ sensitivity of human β-cardiac myosin ATPase activity are consistent with the hypothesis that hypertrophic cardiomyopathies are hypersensitive to Ca2+ activation, and dilated cardiomyopathies are hyposensitive. We also report correlations between ATPase activity at maximum Ca2+ concentrations and conformational changes in TnC measured using a fluorescent probe, which provide evidence that different substitutions perturb the structure of the regulatory complex in different ways. Moreover, we observed changes in protein stability and protein-protein interactions in these mutants. Our results suggest multiple mechanistic pathways to hypertrophic and dilated cardiomyopathies. Finally, we examined a computationally designed mutant, E181K, that is hypersensitive, confirming predictions derived from in silico structural analysis. PMID:25548289

  8. Nomenclature and systems of classification for cardiomyopathy in children.

    PubMed

    Konta, Laura; Franklin, Rodney C G; Kaski, Juan P

    2015-08-01

    There has been a progressive evolution in systems of classification for cardiomyopathy, driven by advances in imaging modalities, disease recognition, and genetics, following initial clinical descriptions in the 1960s. A pathophysiological classification emerged and was endorsed by World Health Organisation Task Forces in 1980 and 1995: dilated, hypertrophic, restrictive, and arrhythmogenic right ventricular cardiomyopathies; subdivided into idiopathic and disease-specific cardiomyopathies. Genetic advances have increasingly linked "idiopathic" phenotypes to specific mutations, although most linkages exhibit highly variable or little genotype-phenotype correlation, confounded by age-dependent changes and varying penetrance. The following two dominant classification systems are currently in use, with advocates in both continents. First, American Heart Association (2006): "A heterogeneous group of diseases of the myocardium associated with mechanical and/or electrical dysfunction that usually exhibit inappropriate ventricular hypertrophy or dilatation due to a variety of causes that frequently are genetic". These are subdivided to those predominantly involving the heart - primary - due to genetic mutation, including ion channelopathies, acquired disease, or mixed; and those with systemic involvement in other organ systems - secondary. Second, European Society of Cardiology (2008): "A myocardial disorder in which heart muscle is structurally and functionally abnormal… sufficient to cause the observed myocardial abnormality", with subdivision to familial and non-familial, excluding ion channelopathies, and split to specific disease subtypes and idiopathic. Further differences exist in the definitions for hypertrophic cardiomyopathy; however, whichever high-level classification is used, the clinical reality remains phenotype driven. Clinical evaluation and diagnostic imaging dominate initial patient contact, revealing diagnostic red flags that determine further

  9. Genetic Variation in Cardiomyopathy and Cardiovascular Disorders.

    PubMed

    McNally, Elizabeth M; Puckelwartz, Megan J

    2015-01-01

    With the wider deployment of massively-parallel, next-generation sequencing, it is now possible to survey human genome data for research and clinical purposes. The reduced cost of producing short-read sequencing has now shifted the burden to data analysis. Analysis of genome sequencing remains challenged by the complexity of the human genome, including redundancy and the repetitive nature of genome elements and the large amount of variation in individual genomes. Public databases of human genome sequences greatly facilitate interpretation of common and rare genetic variation, although linking database sequence information to detailed clinical information is limited by privacy and practical issues. Genetic variation is a rich source of knowledge for cardiovascular disease because many, if not all, cardiovascular disorders are highly heritable. The role of rare genetic variation in predicting risk and complications of cardiovascular diseases has been well established for hypertrophic and dilated cardiomyopathy, where the number of genes that are linked to these disorders is growing. Bolstered by family data, where genetic variants segregate with disease, rare variation can be linked to specific genetic variation that offers profound diagnostic information. Understanding genetic variation in cardiomyopathy is likely to help stratify forms of heart failure and guide therapy. Ultimately, genetic variation may be amenable to gene correction and gene editing strategies.

  10. Experimental models of inherited cardiomyopathy and its therapeutics

    PubMed Central

    Nonaka, Miki; Morimoto, Sachio

    2014-01-01

    Cardiomyopathy is a disease of myocardium categorized into three major forms, hypertrophic (HCM), dilated (DCM) and restrictive cardiomyopathy (RCM), which has recently been demonstrated to be a monogenic disease due to mutations in various proteins expressed in cardiomyocytes. Mutations in HCM and RCM typically increase the myofilament sensitivity to cytoplasmic Ca2+, leading to systolic hyperfunction and diastolic dysfunction. In contrast, mutations in DCM typically decrease the myofilament sensitivity to cytoplasmic Ca2+ and/or force generation/transmission, leading to systolic dysfunction. Creation of genetically-manipulated transgenic and knock-in animals expressing mutant proteins exogenously and endogenously, respectively, in their hearts provides valuable animal models to discover the molecular and cellular mechanisms for pathogenesis and promising therapeutic strategy in vivo. Recently, cardiomyocytes have been differentiated from patient’s induced pluripotent stem cells as a model of inherited cardiomyopathies in vitro. In this review, we provide overview of experimental models of cardiomyopathies with a focus on revealed molecular and cellular pathogenic mechanisms and potential therapeutics. PMID:25548614

  11. Nutrition in Pediatric Cardiomyopathy

    PubMed Central

    Miller, Tracie L.; Neri, Daniela; Extein, Jason; Somarriba, Gabriel; Strickman-Stein, Nancy

    2007-01-01

    Pediatric cardiomyopathies are heterogeneous groups of serious disorders of the heart muscle and are responsible for significant morbidity and mortality among children who have the disease. While enormous improvements have been made in the treatment and survival of children with congenital heart disease, parallel strides have not been made in the outcomes for cardiomyopathies. Thus, ancillary therapies, such as nutrition and nutritional interventions, that may not cure but may potentially improve cardiac function and quality of life, are imperative to consider in children with all types of cardiomyopathy. Growth failure is one of the most significant clinical problems of children with cardiomyopathy with nearly one-third of children with this disorder manifesting some degree of growth failure during the course of their illness. Optimal intake of macronutrients can help improve cardiac function. In addition, several specific nutrients have been shown to correct myocardial abnormalities that often occur with cardiomyopathy and heart failure. In particular, antioxidants that can protect against free radical damage that often occurs in heart failure and nutrients that augment myocardial energy production are important therapies that have been explored more in adults with cardiomyopathy than in the pediatric population. Future research directions should pay particular attention to the effect of overall nutrition and specific nutritional therapies on clinical outcomes and quality of life in children with pediatric cardiomyopathy. PMID:18159216

  12. [Molecular targets and novel pharmacological options to prevent myocardial hypertrophic remodeling].

    PubMed

    Coppini, Raffaele; Ferrantini, Cecilia; Poggesi, Corrado; Mugelli, Alessandro; Olivotto, Iacopo

    2016-03-01

    Myocardial hypertrophic remodeling is a pathophysiological feature of several cardiac conditions and is the hallmark of hypertrophic cardiomyopathy (HCM), the most common monogenic inherited disease of the heart. In recent years, preclinical and clinical studies investigated the underlying molecular mechanisms and intracellular signaling pathways involved in pathologic cardiomyocyte hypertrophy and highlighted a number of possible molecular targets of therapy aimed at preventing its development. Early prevention of myocardial hypertrophic remodeling is particularly sought after in HCM, as current therapeutic strategies are unable to remove the primary cause of disease, i.e. the disease-causing gene mutation. Studies on transgenic animal models or human myocardial samples from patients with HCM identified intracellular calcium overload as a central mechanism driving pathological hypertrophy. In this review, we analyze recent preclinical and clinical studies on animal models and patients with HCM aimed at preventing or modifying hypertrophic myocardial remodeling. Mounting evidence shows that prevention of pathological hypertrophy is a feasible strategy in HCM and will enter the clinical practice in the near future. Considering the close mechanistic similarities between HCM and secondary hypertrophy, these studies are also relevant for the common forms of cardiac hypertrophy, such as hypertensive or valvular heart disease.

  13. Mitochondrial Diseases and Cardiomyopathies.

    PubMed

    Brunel-Guitton, Catherine; Levtova, Alina; Sasarman, Florin

    2015-11-01

    Mitochondrial cardiomyopathies are clinically and genetically heterogeneous. An integrative approach encompassing clinical, biochemical, and molecular investigations is required to reach a specific diagnosis. In this review we summarize the clinical and genetic aspects of mitochondrial disorders associated with cardiomyopathy, including disorders of oxidative phosphorylation. It also describes groups of disorders that, although not usually classified as mitochondrial disorders, stem from defects in mitochondrial function (eg, disorders of β-oxidation and the carnitine cycle), are associated with secondary mitochondrial impairment (eg, organic acidurias), and are important diagnostically because they are treatable. Current biochemical and molecular techniques for the diagnosis of mitochondrial cardiomyopathies are described, and a diagnostic algorithm is proposed, to help clinicians in their approach to cardiomyopathies in the context of mitochondrial diseases.

  14. Types of Cardiomyopathy

    MedlinePlus

    ... Links Related Topics Arrhythmia Heart Failure Heart Murmur Heart Valve Disease Sudden Cardiac Arrest Send a link to NHLBI ... effectively. Dilated cardiomyopathy can lead to heart failure , heart valve disease , irregular heart rate , and blood clots in the ...

  15. Children's Cardiomyopathy Foundation

    MedlinePlus

    ... A Cause for Today… A Cure for Tomorrow” Join Us for 2 Online Events Join CCF for ... benefit programs for children with cardiomyopathy. LEARN MORE Join CCF's Family Network! Become a CCF member and ...

  16. Peripartum cardiomyopathy: a review.

    PubMed

    Bhattacharyya, Anirban; Basra, Sukhdeep Singh; Sen, Priyanka; Kar, Biswajit

    2012-01-01

    Peripartum cardiomyopathy is idiopathic heart failure occurring in the absence of any determinable heart disease during the last month of pregnancy or the first 5 months postpartum. The incidence varies worldwide but is high in developing nations; the cause of the disease might be a combination of environmental and genetic factors. Diagnostic echocardiographic criteria include left ventricular ejection fraction <0.45 or M-mode fractional shortening <30% (or both) and end-diastolic dimension >2.7 cm/m(2). Electrocardiography, magnetic resonance imaging, endomyocardial biopsy, and cardiac catheterization aid in the diagnosis and management of peripartum cardiomyopathy. Cardiac protein assays can also be useful, as suggested by reports of high levels of NT-proBNP, cardiac troponin, tumor necrosis factor-α, interleukin-6, interferon-γ, and C-reactive protein in peripartum cardiomyopathy. The prevalence of mutations associated with familial dilated-cardiomyopathy genes in patients with peripartum cardiomyopathy suggests an overlap in the clinical spectrum of these 2 diseases.Treatment for peripartum cardiomyopathy includes conventional pharmacologic heart-failure therapies-principally diuretics, angiotensin-converting enzyme inhibitors, vasodilators, digoxin, β-blockers, anticoagulants, and peripartum cardiomyopathy-targeted therapies. Therapeutic decisions are influenced by drug-safety profiles during pregnancy and lactation. Mechanical support and transplantation might be necessary in severe cases. Targeted therapies (such as intravenous immunoglobulin, pentoxifylline, and bromocriptine) have shown promise in small trials but require further evaluation. Fortunately, despite a mortality rate of up to 10% and a high risk of relapse in subsequent pregnancies, many patients with peripartum cardiomyopathy recover within 3 to 6 months of disease onset.

  17. The Emerging Role of Cardiovascular Magnetic Resonance Imaging in the Evaluation of Metabolic Cardiomyopathies.

    PubMed

    Mavrogeni, S; Markousis-Mavrogenis, G; Markussis, V; Kolovou, G

    2015-08-01

    The aim of this review is to discuss the role of Cardiovascular Magnetic Resonance (CMR) in the diagnosis, risk stratification, and follow-up of metabolic cardiomyopathies. The classification of myocardial diseases, proposed by WHO/ISFC task force, distinguished specific cardiomyopathies, caused by metabolic disorders, into 4 types: 1) endocrine disorders, 2) storage or infiltration disorders (amyloidosis, hemochromatosis and familial storage disorders), 3) nutritional disorders (Kwashiorkor, beri-beri, obesity, and alcohol), and 4) diabetic heart. Thyroid disease, pheochromocytoma, and growth hormone excess or deficiency may contribute to usually reversible dilated cardiomyopathy. Glucogen storage diseases can be presented with myopathy, liver, and heart failure. Lysosomal storage diseases can provoke cardiac hypertrophy, mimicking hypertrophic cardiomyopathy and arrhythmias. Hereditary hemochromatosis, an inherited disorder of iron metabolism, leads to tissue iron overload in different organs, including the heart. Cardiac amyloidosis is the result of amyloid deposition in the heart, formed from breakdown of normal or abnormal proteins that leads to increased heart stiffness, restrictive cardiomyopathy, and heart failure. Finally, nutritional disturbances and metabolic diseases, such as Kwashiorkor, beri-beri, obesity, alcohol consumption, and diabetes mellitus may also lead to severe cardiac dysfunction. CMR, through its capability to reliably assess anatomy, function, inflammation, rest-stress myocardial perfusion, myocardial fibrosis, aortic distensibility, iron and/or fat deposition can serve as an excellent tool for early diagnosis of heart involvement, risk stratification, treatment evaluation, and long term follow-up of patients with metabolic cardiomyopathies.

  18. Stress-related cardiomyopathies

    PubMed Central

    2011-01-01

    Stress-related cardiomyopathies can be observed in the four following situations: Takotsubo cardiomyopathy or apical ballooning syndrome; acute left ventricular dysfunction associated with subarachnoid hemorrhage; acute left ventricular dysfunction associated with pheochromocytoma and exogenous catecholamine administration; acute left ventricular dysfunction in the critically ill. Cardiac toxicity was mediated more by catecholamines released directly into the heart via neural connection than by those reaching the heart via the bloodstream. The mechanisms underlying the association between this generalized autonomic storm secondary to a life-threatening stress and myocardial toxicity are widely discussed. Takotsubo cardiomyopathy has been reported all over the world and has been acknowledged by the American Heart Association as a form of reversible cardiomyopathy. Four "Mayo Clinic" diagnostic criteria are required for the diagnosis of Takotsubo cardiomyopathy: 1) transient left ventricular wall motion abnormalities involving the apical and/or midventricular myocardial segments with wall motion abnormalities extending beyond a single epicardial coronary artery distribution; 2) absence of obstructive epicardial coronary artery disease that could be responsible for the observed wall motion abnormality; 3) ECG abnormalities, such as transient ST-segment elevation and/or diffuse T wave inversion associated with a slight troponin elevation; and 4) the lack of proven pheochromocytoma and myocarditis. ECG changes and LV dysfunction occur frequently following subarachnoid hemorrhage and ischemic stroke. This entity, referred as neurocardiogenic stunning, was called neurogenic stress-related cardiomyopathy. Stress-related cardiomyopathy has been reported in patients with pheochromocytoma and in patients receiving intravenous exogenous catecholamine administration. The role of a huge increase in endogenous and/or exogenous catecholamine level in critically ill patients

  19. Loss of MYC and E-box3 binding contributes to defective MYC-mediated transcriptional suppression of human MC-let-7a-1~let-7d in glioblastoma

    PubMed Central

    Wang, Zifeng; Lin, Sheng; Zhang, Ji; Xu, Zhenhua; Xiang, Yu; Yao, Hong; Ge, Lei; Xie, Dan; Kung, Hsiang-fu; Lu, Gang; Poon, Wai Sang; Liu, Quentin; Lin, Marie Chia-mi

    2016-01-01

    Previously, we reported that MYC oncoprotein down-regulates the transcription of human MC-let-7a-1~let-7d microRNA cluster in hepatocarcinoma (HCC). Surprisingly, in silico analysis indicated that let-7 miRNA expression levels are not reduced in glioblastoma (GBM). Here we investigated the molecular basis of this differential expression. Using human GBM U87 and U251 cells, we first demonstrated that forced over-expression of MYC indeed could not down-regulate the expression of human MC-let-7a-1~let-7d microRNA cluster in GBM. Furthermore, analysis of MC-let-7a-1~let-7d promoter in GBM indicated that MYC failed to inhibit the promoter activity. Pearson's correlation and Linear Regression analysis using the expression data from GSE55092 (HCC) and GSE4290 (GBM) demonstrated a converse relationship of MC-let-7a-1~let-7d and MYC only in HCC but not in GBM. To understand the underlying mechanisms, we examined whether MYC could bind to the non-canonical E-box 3 located in the promoter of MC-let-7a-1~let-7d. Results from both chromatin immune-precipitation (ChIP) and super-shift assays clearly demonstrated the loss of MYC and E-box 3 binding in GBM, suggesting for the first time that a defective MYC and E-box3 binding in GBM is responsible for the differential MYC mediated transcriptional inhibition of MC-let-7a-1~let-7d and potentially other tumor suppressors. MYC and let-7 are key oncoprotein and tumor suppressor, respectively. Understanding the molecular mechanisms of their regulations will provide new insight and have important implications in the therapeutics of GBM as well as other cancers. PMID:27409345

  20. Loss of MYC and E-box3 binding contributes to defective MYC-mediated transcriptional suppression of human MC-let-7a-1~let-7d in glioblastoma.

    PubMed

    Wang, Zifeng; Lin, Sheng; Zhang, Ji; Xu, Zhenhua; Xiang, Yu; Yao, Hong; Ge, Lei; Xie, Dan; Kung, Hsiang-Fu; Lu, Gang; Poon, Wai Sang; Liu, Quentin; Lin, Marie Chia-Mi

    2016-08-30

    Previously, we reported that MYC oncoprotein down-regulates the transcription of human MC-let-7a-1~let-7d microRNA cluster in hepatocarcinoma (HCC). Surprisingly, in silico analysis indicated that let-7 miRNA expression levels are not reduced in glioblastoma (GBM). Here we investigated the molecular basis of this differential expression. Using human GBM U87 and U251 cells, we first demonstrated that forced over-expression of MYC indeed could not down-regulate the expression of human MC-let-7a-1~let-7d microRNA cluster in GBM. Furthermore, analysis of MC-let-7a-1~let-7d promoter in GBM indicated that MYC failed to inhibit the promoter activity. Pearson's correlation and Linear Regression analysis using the expression data from GSE55092 (HCC) and GSE4290 (GBM) demonstrated a converse relationship of MC-let-7a-1~let-7d and MYC only in HCC but not in GBM. To understand the underlying mechanisms, we examined whether MYC could bind to the non-canonical E-box 3 located in the promoter of MC-let-7a-1~let-7d. Results from both chromatin immune-precipitation (ChIP) and super-shift assays clearly demonstrated the loss of MYC and E-box 3 binding in GBM, suggesting for the first time that a defective MYC and E-box3 binding in GBM is responsible for the differential MYC mediated transcriptional inhibition of MC-let-7a-1~let-7d and potentially other tumor suppressors. MYC and let-7 are key oncoprotein and tumor suppressor, respectively. Understanding the molecular mechanisms of their regulations will provide new insight and have important implications in the therapeutics of GBM as well as other cancers.

  1. Treatment of Chagas Cardiomyopathy

    PubMed Central

    Botoni, Fernando A.; Ribeiro, Antonio Luiz P.; Marinho, Carolina Coimbra; Lima, Marcia Maria Oliveira; Nunes, Maria do Carmo Pereira; Rocha, Manoel Otávio C.

    2013-01-01

    Chagas' disease (ChD), caused by the protozoa Trypanosoma cruzi (T. cruzi), was discovered and described by the Brazilian physician Carlos Chagas in 1909. After a century of original description, trypanosomiasis still brings much misery to humanity and is classified as a neglected tropical disease prevalent in underdeveloped countries, particularly in South America. It is an increasing worldwide problem due to the number of cases in endemic areas and the migration of infected subjects to more developed regions, mainly North America and Europe. Despite its importance, chronic chagas cardiomyopathy (CCC) pathophysiology is yet poorly understood, and independently of its social, clinical, and epidemiological importance, the therapeutic approach of CCC is still transposed from the knowledge acquired from other cardiomyopathies. Therefore, the objective of this review is to describe the treatment of Chagas cardiomyopathy with emphasis on its peculiarities. PMID:24350293

  2. Alcoholic cardiomyopathy: Pathophysiologic insights

    PubMed Central

    Piano, Mariann R.; Phillips, Shane A.

    2014-01-01

    Alcoholic cardiomyopathy is a specific heart muscle disease found in individuals with a history of long-term heavy alcohol consumption. Alcoholic cardiomyopathy is associated with a number of adverse histological, cellular, and structural changes within the myocardium. Several mechanisms are implicated in mediating the adverse effects of ethanol, including the generation of oxidative stress, apoptotic cell death, impaired mitochondrial bioenergetics/stress, derangements in fatty acid metabolism and transport, and accelerated protein catabolism. In this review, we discuss the evidence for such mechanisms and present the potential importance of drinking patterns, genetic susceptibility, nutritional factors, race, and sex. The purpose of this review is to provide a mechanistic paradigm for future research in the area of alcoholic cardiomyopathy. PMID:24671642

  3. Arrhythmias in peripartum cardiomyopathy.

    PubMed

    Honigberg, Michael C; Givertz, Michael M

    2015-06-01

    Peripartum cardiomyopathy (PPCM) is a complication of late pregnancy and the early postpartum period characterized by dilated cardiomyopathy and heart failure with reduced ejection fraction. Approximately half of women fail to recover left ventricular function. Standard management of heart failure is indicated, with some exceptions for women who are predelivery or breastfeeding. Atrial and ventricular arrhythmias are reported in PPCM, but the frequency of arrhythmias in this condition is not well characterized. Management of PPCM-associated arrhythmias may include antiarrhythmic drugs, catheter ablation, and wearable or implantable cardioverter-defibrillators. Further research is needed on the prevalence, natural history, and optimal management of arrhythmias in PPCM.

  4. Dilated cardiomyopathy: the complexity of a diverse genetic architecture.

    PubMed

    Hershberger, Ray E; Hedges, Dale J; Morales, Ana

    2013-09-01

    Remarkable progress has been made in understanding the genetic basis of dilated cardiomyopathy (DCM). Rare variants in >30 genes, some also involved in other cardiomyopathies, muscular dystrophy, or syndromic disease, perturb a diverse set of important myocardial proteins to produce a final DCM phenotype. Large, publicly available datasets have provided the opportunity to evaluate previously identified DCM-causing mutations, and to examine the population frequency of sequence variants similar to those that have been observed to cause DCM. The frequency of these variants, whether associated with dilated or hypertrophic cardiomyopathy, is greater than estimates of disease prevalence. This mismatch might be explained by one or more of the following possibilities: that the penetrance of DCM-causing mutations is lower than previously thought, that some variants are noncausal, that DCM prevalence is higher than previously estimated, or that other more-complex genomics underlie DCM. Reassessment of our assumptions about the complexity of the genomic and phenomic architecture of DCM is warranted. Much about the genomic basis of DCM remains to be investigated, which will require comprehensive genomic studies in much larger cohorts of rigorously phenotyped probands and family members than previously examined.

  5. Molecular profiling of dilated cardiomyopathy that progresses to heart failure

    PubMed Central

    Burke, Michael A.; Chang, Stephen; Wakimoto, Hiroko; Gorham, Joshua M.; Conner, David A.; Christodoulou, Danos C.; Parfenov, Michael G.; DePalma, Steve R.; Eminaga, Seda; Konno, Tetsuo; Seidman, Jonathan G.; Seidman, Christine E.

    2016-01-01

    Dilated cardiomyopathy (DCM) is defined by progressive functional and structural changes. We performed RNA-seq at different stages of disease to define molecular signaling in the progression from pre-DCM hearts to DCM and overt heart failure (HF) using a genetic model of DCM (phospholamban missense mutation, PLNR9C/+). Pre-DCM hearts were phenotypically normal yet displayed proliferation of nonmyocytes (59% relative increase vs. WT, P = 8 × 10–4) and activation of proinflammatory signaling with notable cardiomyocyte-specific induction of a subset of profibrotic cytokines including TGFβ2 and TGFβ3. These changes progressed through DCM and HF, resulting in substantial fibrosis (17.6% of left ventricle [LV] vs. WT, P = 6 × 10–33). Cardiomyocytes displayed a marked shift in metabolic gene transcription: downregulation of aerobic respiration and subsequent upregulation of glucose utilization, changes coincident with attenuated expression of PPARα and PPARγ coactivators -1α (PGC1α) and -1β, and increased expression of the metabolic regulator T-box transcription factor 15 (Tbx15). Comparing DCM transcriptional profiles with those in hypertrophic cardiomyopathy (HCM) revealed similar and distinct molecular mechanisms. Our data suggest that cardiomyocyte-specific cytokine expression, early fibroblast activation, and the shift in metabolic gene expression are hallmarks of cardiomyopathy progression. Notably, key components of these profibrotic and metabolic networks were disease specific and distinguish DCM from HCM. PMID:27239561

  6. Neonatal cardiomyopathies and metabolic crises due to oxidative phosphorylation defects.

    PubMed

    Schiff, Manuel; Ogier de Baulny, Hélène; Lombès, Anne

    2011-08-01

    Neonatal cardiomyopathies due to mitochondrial oxidative phosphorylation (OXPHOS) defects are extremely severe conditions which can be either isolated or included in a multi-organ disease, with or without metabolic crises, of which profound lactic acidosis is the prominent feature. Cardiomyopathy is more often hypertrophic than dilated. Antenatal manifestations such as fetal cardiomyopathy, arrhythmia and/or hydrops have been reported. Pathophysiological mechanisms are complex, going beyond ATP deficiency of the high-energy-consuming neonatal myocardium. Birth is a key metabolic period when the myocardium switches ATP production from anaerobic glycolysis to mitochondrial fatty acid oxidation and OXPHOS. Heart-specificity of the defect may be related to the specific localization of the defect, to the high myocardium dependency on OXPHOS, and/or to interaction between the primary genetic alteration and other factors such as modifier genes. Therapeutic options are limited but standardized diagnostic procedures are mandatory to confirm the OXPHOS defect and to identify its causal mutation, allowing genetic counseling and potential prenatal diagnosis.

  7. Deficiency of the mitochondrial phosphate carrier presenting as myopathy and cardiomyopathy in a family with three affected children.

    PubMed

    Mayr, Johannes A; Zimmermann, Franz A; Horváth, Rita; Schneider, Hans-Christian; Schoser, Benedikt; Holinski-Feder, Elke; Czermin, Birgit; Freisinger, Peter; Sperl, Wolfgang

    2011-11-01

    In a family three children presented with severe neonatal lactic acidosis, hypertrophic cardiomyopathy and generalised muscular hypotonia. One child died in infancy, two survived a clinically severe neonatal period. At an age of 9 and 17years, respectively, they present with exercise intolerance, proximal muscle weakness, non-progressive hypertrophic cardiomyopathy and normal mental development. In a muscle biopsy normal activity of respiratory chain enzymes was found; however the amount of the mitochondrial phosphate carrier was decreased. This protein is expressed in two tissue-specific isoforms generated by mutually exclusive alternative splicing of the SLC25A3 gene transcript. We identified a homozygous mutation c.158-9A>G located in the 5'-intron next to exon 3A specific for heart and skeletal muscle. This creates a novel splice site resulting in a more than 95% decrease of the wild type allele.

  8. Cardiomyopathy Following Latrodectus Envenomation

    PubMed Central

    Levine, Michael; Canning, Josh; Chase, Robyn; Ruha, Anne-Michelle

    2010-01-01

    Latrodectus envenomations are common throughout the United States and the world. While many envenomations can result in catecholamine release with resultant hypertension and tachycardia, myocarditis is very rare. We describe a case of a 22-year-old male who sustained a Latrodectus envenomation complicated by cardiomyopathy. PMID:21293781

  9. Genetics Home Reference: familial restrictive cardiomyopathy

    MedlinePlus

    ... Home Health Conditions familial restrictive cardiomyopathy familial restrictive cardiomyopathy Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Familial restrictive cardiomyopathy is a genetic form of heart disease. For ...

  10. Hypertrophic lupus vulgaris: an unusual presentation.

    PubMed

    Jain, Vijay K; Aggarwal, Kamal; Jain, Sarika; Singh, Sunita

    2009-07-01

    Lupus vulgaris is the most common form of cutaneous tuberculosis occurring in previously sensitized individuals with a high degree of tuberculin sensitivity. Various forms including plaque, ulcerative, hypertrophic, vegetative, papular, and nodular forms have been described. A 30-year-old male patient presented with a very large hypertrophic lupus vulgaris lesion over left side of chest since 22 years. Histopathological examination showed granulomatous infiltration without caseation necrosis. The Mantoux reaction was strongly positive. Hypertrophic lupus vulgaris of such a giant size and that too at an unusual site is extremely rare and hence is being reported.

  11. MELAS syndrome and cardiomyopathy: linking mitochondrial function to heart failure pathogenesis.

    PubMed

    Hsu, Ying-Han R; Yogasundaram, Haran; Parajuli, Nirmal; Valtuille, Lucas; Sergi, Consolato; Oudit, Gavin Y

    2016-01-01

    Heart failure remains an important clinical burden, and mitochondrial dysfunction plays a key role in its pathogenesis. The heart has a high metabolic demand, and mitochondrial function is a key determinant of myocardial performance. In mitochondrial disorders, hypertrophic remodeling is the early pattern of cardiomyopathy with progression to dilated cardiomyopathy, conduction defects and ventricular pre-excitation occurring in a significant proportion of patients. Cardiac dysfunction occurs in approximately a third of patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome, a stereotypical example of a mitochondrial disorder leading to a cardiomyopathy. We performed unique comparative ultrastructural and gene expression in a MELAS heart compared with non-failing controls. Our results showed a remarkable increase in mitochondrial inclusions and increased abnormal mitochondria in MELAS cardiomyopathy coupled with variable sarcomere thickening, heterogeneous distribution of affected cardiomyocytes and a greater elevation in the expression of disease markers. Investigation and management of patients with mitochondrial cardiomyopathy should follow the well-described contemporary heart failure clinical practice guidelines and include an important role of medical and device therapies. Directed metabolic therapy is lacking, but current research strategies are dedicated toward improving mitochondrial function in patients with mitochondrial disorders.

  12. Laser application for hypertrophic rhinitis

    NASA Astrophysics Data System (ADS)

    Inouye, Tetsuzo; Tanabe, Tetsuya; Nakanoboh, Manabu; Ogura, Masami

    1995-05-01

    The CO2 and KTP/532 lasers have been used in the treatment of an allergic and hypertrophic rhinitis for the past several years. As we know, the laser enables a surgeon to perform the operation with minimum hemorrhage and minimized pain, during and after the procedure. Additionally many of these operations can be performed under local anesthesia instead of general anesthesia, on an outpatient basis. The laser is used to irradiate the mucous membranes of the inferior turbinates. Vaporization and cutting is easily done. Post operative management of the local operated area is easy. The advantages of laser surgery over regular surgical techniques are supreme for intranasal operations when performed under local anesthesia.

  13. Current Indications for Implantable Cardioverter Defibrillators in Non-Ischemic Cardiomyopathies and Channelopathies.

    PubMed

    González-Torrecilla, Esteban; Arenal, Angel; Atienza, Felipe; Datino, Tomás; Bravo, Loreto; Ruiz, Pablo; Ávila, Pablo; Fernández-Avilés, Francisco

    2015-01-01

    Current indications for implantable cardioverter defibrillators (ICDs) in patients with channelopathies and cardiomyopathies of non-ischemic origin are mainly based on non-randomized evidence. In patients with nonischemic dilated cardiomyopathy (NIDCM), there is a tendency towards a beneficial effect on total mortality of ICD therapy in patients with significant left ventricular (LV) dysfunction. Although an important reduction in sudden cardiac death (SCD) seems to be clearly demonstrated in these patients, a net beneficial effect on total mortality is unclear mostly in cases with good functional status. Risk stratification has been changing over the last two decades in patients with hypertrophic cardiomyopathy (HCM). Its risk profile has been delineated in parallel with the beneficial effect of ICD in high risk patients. Observational results based on "appropriate" ICD interventions do support its usefulness both in primary and secondary SCD prevention in these patients. Novel risk models quantify the rate of sudden cardiac death in these patients on individual basis. Less clear risk stratification is available for cases of arrhythmogenic right ventricular cardiomyopathy (ARVC) and in other uncommon familiar cardiomyopathies. Main features of risk stratification vary among the different channelopathies (long QT syndrome -LQTS-, Brugada syndrome, etc) with great debate on the management of asymptomatic patients. For most familiar cardiomyopathies, ICD therapy is the only accepted strategy in the prevention of SCD. So far, genetic testing has a limited role in risk evaluation and management of the individual patient. This review aims to summarize these criticisms and to refine the current indications of ICD implantation in patients with cardiomyopathies and major channelopathies.

  14. Peripartum cardiomyopathy: a review

    PubMed Central

    Capriola, Michael

    2013-01-01

    Peripartum cardiomyopathy (PPCM) is a form of dilated cardiomyopathy of unclear etiology affecting women without preexisting heart disease during the last month of pregnancy or during the first 5 months postpartum. Its incidence shows marked geographic and ethnic variation, being most common in Africa and among women of African descent. Most women present in the first month postpartum with typical heart failure symptoms such as dyspnea, lower extremity edema, and fatigue. These symptoms are often initially erroneously diagnosed as part of the normal puerperal process. Diagnosis can be aided by the finding of a significantly elevated serum brain natriuretic peptide. The etiology of PPCM is unclear; however, recent research suggests abnormal prolactin metabolism is seminal in its development, and prolactin antagonism with bromocriptine shows promise as a novel treatment for PPCM. PMID:23300351

  15. [Tachycardia-induced cardiomyopathy].

    PubMed

    Povolný, Jan

    2015-01-01

    Cardiomyopathy is a heterogeneous group of diseases of heart muscle accompanied with impaired cardiac function. Tachycardia-induced cardiomyopathy (TIC) is caused by prolonged tachycardia leading to dilatation and systolic dysfunction with clinical manifestation of heart failure. This state is reversible after normalization of heart rate. The diagnosis is usually made retrospectively after normalization of heart rate and recovery of left ventricular function (LVF). More than 100 years after the first documented case (described in 1913 in a young patient with atrial fibrillation and symptoms of heart failure [25]) is still limited knowledge of pathophysiological mechanisms. The most common arrhythmias responsible for the TIC include atrial fibrillation [1,2], atrial flutter [3], incessant supraventricular tachycardia [4], ventricular tachycardia (VT) [5] and frequent ventricular extrasystoles (VES) [6]. TIC detection and therapeutic intervention is crucial considering potential reversibility of tachycardia. Current options of treatment involve drug therapy and surgical or catheter ablation.

  16. [The clinical practice guidelines of the Sociedad Española de Cardiología on cardiomyopathies and myocarditis].

    PubMed

    Galve Basilio, E; Alfonso Manterola, F; Ballester Rodés, M; Castro Beiras, A; Fernández de Soria Pantoja, R; Penas Lado, M; Sánchez Domínguez, J

    2000-03-01

    Myocardial diseases are a extraordinarily heterogeneous group of processes that only have in common the fact that they involve heart muscle and that they cause a wide spectrum of myocardial dysfunction. The approach of the management and treatment of the cardiomyopathies is a continuous matter of discussion because the vast majority of alternatives in this field have not been based on the best scientific possible evidence and, since except for the case of heart failure associated with dilated cardiomyopathy. The majority of different options have not been studied by means of large (or even small) randomized trials. Nevertheless, this chapter has tried to provide the reader with different approaches on how to deal with important clinical problems in dilated, hypertrophic and restrictive cardiomyopathies, and in myocarditis as well. For this, we have utilized the most relevant information found coupled with our best clinical judgment, although we admit that many of the clinical recommendations can be controversial.

  17. Decade in review--cardiomyopathies: Cardiomyopathy on the move.

    PubMed

    Yacoub, Magdi H

    2014-11-01

    Since Wallace Brigden first used the term 'cardiomyopathy' in 1952, this group of diseases has continued to attract the interest of clinicians, researchers, and importantly, patients. The past decade has seen a substantial accumulation of knowledge relating to various cardiomyopathies, which has partially lifted the mystery surrounding this topic.

  18. Role of neuropeptides in cardiomyopathies.

    PubMed

    Dvorakova, Magdalena Chottova; Kruzliak, Peter; Rabkin, Simon W

    2014-11-01

    The role of neuropeptides in cardiomyopathy-associated heart failure has been garnering more attention. Several neuropeptides--Neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), calcitonin gene related peptide (CGRP), substance P (SP) and their receptors have been studied in the various types of cardiomyopathies. The data indicate associations with the strength of the association varying depending on the kind of neuropeptide and the nature of the cardiomyopathy--diabetic, ischemic, inflammatory, stress-induced or restrictive cardiomyopathy. Several neuropeptides appear to alter regulation of genes involved in heart failure. Demonstration of an association is an essential first step in proving causality or establishing a role for a factor in a disease. Understanding the complexity of neuropeptide function should be helpful in establishing new or optimal therapeutic strategies for the treatment of heart failure in cardiomyopathies.

  19. Etiology of amyloidosis determines myocardial 99mTc-DPD uptake in amyloidotic cardiomyopathy.

    PubMed

    Longhi, Simone; Bonfiglioli, Rachele; Obici, Laura; Gagliardi, Christian; Milandri, Agnese; Lorenzini, Massimiliano; Guidalotti, Pier Luigi; Merlini, Giampaolo; Rapezzi, Claudio

    2015-05-01

    Tc-DPD (Tc-3,3-diphosphono-1,2-propanodicarboxylic acid) has a high affinity for transthyretin (TTR)-infiltrated myocardium, allowing a differential diagnosis with light chain cardiac amyloidosis and other nonamyloidotic cardiomyopathies with a hypertrophic phenotype, in which myocardial tracer uptake is low or absent. Myocardial bone tracer uptake in the rarer forms of amyloidosis (eg, apolipoprotein-related) has been rarely studied. We present 4 cases of cardiac amyloidosis that underwent Tc-DPD scintigraphy; myocardial DPD uptake was present in patients with ATTR, wtTTR and apolipoprotein AI and negative in cases with AL and apolipoprotein AII-related disease.

  20. Cardiac involvement of primary hyperoxaluria accompanied by non-compaction cardiomyopathy and patent ductus arteriosus.

    PubMed

    Arat, Nurcan; Akyıldız, Murat; Tellioğlu, Gürkan; Tokat, Yaman

    2015-04-01

    Primary hyperoxaluria is a rare hereditary metabolic disorder resulting in accumulation of calcium oxalate in visceral organs, including the heart. We report a 19-year-old male with non- compaction cardiomyopathy combined with patent ductus arteriosus awaiting combined liver-kidney transplantation for primary hyperoxaluria. After surgical closure of the patent ductus arteriosus, the patient underwent a successful renal and subsequent liver transplantation. The presence of hypertrophic cardiomyopathy in hyperoxaluria patients has been reported before, but this is the first report of non-compaction myocardium with patent ductus arteriosus in a patient with primary hyperoxaluria. At the third month after combined liver and renal transplantation, improvement in cardiac functions were observed. Primary hyperoxaluria is a clinical entity to be taken into consideration in differential diagnosis of hypertrophied myocardium with high myocardial echocardiographic intensity. In cases of hyperoxaluria, additional congenital abnormalities may complicate the clinical picture.

  1. MTO1-Deficient Mouse Model Mirrors the Human Phenotype Showing Complex I Defect and Cardiomyopathy

    PubMed Central

    Becker, Lore; Kling, Eva; Schiller, Evelyn; Zeh, Ramona; Schrewe, Anja; Hölter, Sabine M.; Mossbrugger, Ilona; Calzada-Wack, Julia; Strecker, Valentina; Wittig, Ilka; Dumitru, Iulia; Wenz, Tina; Bender, Andreas; Aichler, Michaela; Janik, Dirk; Neff, Frauke; Walch, Axel; Quintanilla-Fend, Leticia; Floss, Thomas; Bekeredjian, Raffi; Gailus-Durner, Valérie; Fuchs, Helmut; Wurst, Wolfgang; Meitinger, Thomas; Prokisch, Holger; de Angelis, Martin Hrabě; Klopstock, Thomas

    2014-01-01

    Recently, mutations in the mitochondrial translation optimization factor 1 gene (MTO1) were identified as causative in children with hypertrophic cardiomyopathy, lactic acidosis and respiratory chain defect. Here, we describe an MTO1-deficient mouse model generated by gene trap mutagenesis that mirrors the human phenotype remarkably well. As in patients, the most prominent signs and symptoms were cardiovascular and included bradycardia and cardiomyopathy. In addition, the mutant mice showed a marked worsening of arrhythmias during induction and reversal of anaesthesia. The detailed morphological and biochemical workup of murine hearts indicated that the myocardial damage was due to complex I deficiency and mitochondrial dysfunction. In contrast, neurological examination was largely normal in Mto1-deficient mice. A translational consequence of this mouse model may be to caution against anaesthesia-related cardiac arrhythmias which may be fatal in patients. PMID:25506927

  2. Alterations in sarcomere function modify the hyperplastic to hypertrophic transition phase of mammalian cardiomyocyte development

    PubMed Central

    Nixon, Benjamin R.; Williams, Alexandra F.; Glennon, Michael S.; de Feria, Alejandro E.; Sebag, Sara C.; Baldwin, H. Scott; Becker, Jason R.

    2017-01-01

    It remains unclear how perturbations in cardiomyocyte sarcomere function alter postnatal heart development. We utilized murine models that allowed manipulation of cardiac myosin-binding protein C (MYBPC3) expression at critical stages of cardiac ontogeny to study the response of the postnatal heart to disrupted sarcomere function. We discovered that the hyperplastic to hypertrophic transition phase of mammalian heart development was altered in mice lacking MYBPC3 and this was the critical period for subsequent development of cardiomyopathy. Specifically, MYBPC3-null hearts developed evidence of increased cardiomyocyte endoreplication, which was accompanied by enhanced expression of cell cycle stimulatory cyclins and increased phosphorylation of retinoblastoma protein. Interestingly, this response was self-limited at later developmental time points by an upregulation of the cyclin-dependent kinase inhibitor p21. These results provide valuable insights into how alterations in sarcomere protein function modify postnatal heart development and highlight the potential for targeting cell cycle regulatory pathways to counteract cardiomyopathic stimuli. PMID:28239655

  3. [Anaesthetic management of caesarean section in pregnancy with diabetes and hypertrophic myocardiopathy with restrictive diastolic dysfunction].

    PubMed

    Holgado, C M; Coves, S

    2013-02-01

    Haemodynamic changes that occur during pregnancy are maximal between 28 and 34 weeks. In the pregnant woman with several associated diseases, such as hypertensive myocardiopathy and pre-gestational diabetes, these changes can lead to a difficult control of pulmonary hypertension and acute pulmonary oedema. We report the case of a pregnant woman with long term type 1 diabetes mellitus who suffered pre-eclampsia in a previous pregnancy, and since then developed hypertensive cardiomyopathy. She was admitted at 30 week gestation for metabolic and blood pressure control, and developed congestive cardiac failure after the administration of betamethasone for foetal lung maturity. A transthoracic echocardiogram showed a non-dilated hypertrophic left ventricle with good systolic function, restrictive diastolic dysfunction and moderate pulmonary arterial hypertension. When her general condition improved, we performed a caesarean section under regional anaesthesia to prevent the complications of pulmonary and systemic hypertension. We present the anaesthetic management and resolution of complications after oxytocin administration.

  4. Hypertrophic pachymeningitis accompanying neuromyelitis optica spectrum disorder: A case report.

    PubMed

    Kon, Tomoya; Nishijima, Haruo; Haga, Rie; Funamizu, Yukihisa; Ueno, Tatsuya; Arai, Akira; Suzuki, Chieko; Nunomura, Jin-ichi; Baba, Masayuki; Takahashi, Toshiyuki; Tomiyama, Masahiko

    2015-10-15

    We report a case of idiopathic cerebral hypertrophic pachymeningitis accompanying neuromyelitis optica spectrum disorder. No other identifiable cause of pachymeningitis was detected. Corticosteroid therapy was effective for both diseases. Hypertrophic pachymeningitis is closely related to autoimmune inflammatory disease of the central nervous system. This case supports the hypothesis that hypertrophic pachymeningitis can be a rare comorbidity of neuromyelitis optica spectrum disorder.

  5. Defining phenotypes and disease progression in sarcomeric cardiomyopathies: contemporary role of clinical investigations.

    PubMed

    Olivotto, Iacopo; d'Amati, Giulia; Basso, Cristina; Van Rossum, Albert; Patten, Monica; Emdin, Michele; Pinto, Yigal; Tomberli, Benedetta; Camici, Paolo G; Michels, Michelle

    2015-04-01

    Mutations in cardiac sarcomere protein genes are associated with a variety of clinical phenotypes, including hypertrophic (HCM), dilated (DCM), and restrictive (RCM) cardiomyopathy as well as left ventricular non-compaction, with the overlap of morpho-functional manifestations in individual patients and families. Over time, initial phenotypes may undergo profound changes which determine clinical course and disease progression. Although genetic defects causing HCM and DCM have opposite effects at the myofilament level, a number of downstream maladaptive mechanisms, ranging from microvascular dysfunction and ischaemia to myocardial fibrosis and from diastolic dysfunction to abnormal sympathetic activation and arrhythmogenesis, seem to recur in sarcomeric cardiomyopathies, independent of the presenting phenotype. The extent and rate at which each of these features occur and evolve may be radically different in each form of cardiomyopathy, determining a clinical heterogeneity that is not only cross-sectional, but also longitudinal, i.e. time-related. Timely and sensitive detection of these long-term modifications in the clinical setting is a key to preventing advanced disease and identifying novel therapeutic targets. The present review evaluates the contribution of contemporary technology to pre-clinical diagnosis, characterization of phenotypes, and assessment of disease progression in sarcomere cardiomyopathies, including echocardiography, positron emission tomography, magnetic resonance, pathology, and circulating biomarkers.

  6. Genetics of inherited cardiomyopathy.

    PubMed

    Jacoby, Daniel; McKenna, William J

    2012-02-01

    During the past two decades, numerous disease-causing genes for different cardiomyopathies have been identified. These discoveries have led to better understanding of disease pathogenesis and initial steps in the application of mutation analysis in the evaluation of affected individuals and their family members. As knowledge of the genetic abnormalities, and insight into cellular and organ biology has grown, so has appreciation of the level of complexity of interaction between genotype and phenotype across disease states. What were initially thought to be one-to-one gene-disease correlates have turned out to display important relational plasticity dependent in large part on the genetic and environmental backgrounds into which the genes of interest express. The current state of knowledge with regard to genetics of cardiomyopathy represents a starting point to address the biology of disease, but is not yet developed sufficiently to supplant clinically based classification systems or, in most cases, to guide therapy to any significant extent. Future work will of necessity be directed towards elucidation of the biological mechanisms of both rare and common gene variants and environmental determinants of plasticity in the genotype-phenotype relationship with the ultimate goal of furthering our ability to identify, diagnose, risk stratify, and treat this group of disorders which cause heart failure and sudden death in the young.

  7. Takotsubo cardiomyopathy (Broken heart syndrome).

    PubMed

    Javed, Aqib; Chitkara, Kamal; Mahmood, Arslan; Kainat, Aleesha

    2015-11-01

    Takotsubo cardiomyopathy is an acute reversible cardiomyopathy characterised by transient regional left ventricular (LV) motion abnormalities. It is diagnosed on a coronary angiography and left ventriculography. We report the case of a 50-year-old lady who presented with sudden onset of chest pain, with no history of cardiac disease and no risk factors. Remarkably though, she had lost her husband the previous night. Coronary and LV angiography was done which revealed findings typical of takotsubo cardiomyopathy. We report this case for its rarity. Informed consent was taken from the patient before undertaking and reporting this study.

  8. A Review of the Giant Protein Titin in Clinical Molecular Diagnostics of Cardiomyopathies

    PubMed Central

    Gigli, Marta; Begay, Rene L.; Morea, Gaetano; Graw, Sharon L.; Sinagra, Gianfranco; Taylor, Matthew R. G.; Granzier, Henk; Mestroni, Luisa

    2016-01-01

    Titin (TTN) is known as the largest sarcomeric protein that resides within the heart muscle. Due to alternative splicing of TTN, the heart expresses two major isoforms (N2B and N2BA) that incorporate four distinct regions termed the Z-line, I-band, A-band, and M-line. Next-generation sequencing allows a large number of genes to be sequenced simultaneously and provides the opportunity to easily analyze giant genes such as TTN. Mutations in the TTN gene can cause cardiomyopathies, in particular dilated cardiomyopathy (DCM). DCM is the most common form of cardiomyopathy, and it is characterized by systolic dysfunction and dilation of the left ventricle. TTN truncating variants have been described as the most common cause of DCM, while the real impact of TTN missense variants in the pathogenesis of DCM is still unclear. In a recent population screening study, rare missense variants potentially pathogenic based on bioinformatic filtering represented only 12.6% of the several hundred rare TTN missense variants found, suggesting that missense variants are very common in TTN and are frequently benign. The aim of this review is to understand the clinical role of TTN mutations in DCM and in other cardiomyopathies. Whereas TTN truncations are common in DCM, there is evidence that TTN truncations are rare in the hypertrophic cardiomyopathy (HCM) phenotype. Furthermore, TTN mutations can also cause arrhythmogenic right ventricular cardiomyopathy (ARVC) with distinct clinical features and outcomes. Finally, the identification of a rare TTN missense variant cosegregating with the restrictive cardiomyopathy (RCM) phenotype suggests that TTN is a novel disease-causing gene in this disease. Clinical diagnostic testing is currently able to analyze over 100 cardiomyopathy genes, including TTN; however, the size and presence of extensive genetic variation in TTN presents clinical challenges in determining significant disease-causing mutations. This review discusses the current

  9. Cardiac deficiency of single cytochrome oxidase assembly factor scox induces p53-dependent apoptosis in a Drosophila cardiomyopathy model.

    PubMed

    Martínez-Morentin, Leticia; Martínez, Lidia; Piloto, Sarah; Yang, Hua; Schon, Eric A; Garesse, Rafael; Bodmer, Rolf; Ocorr, Karen; Cervera, Margarita; Arredondo, Juan J

    2015-07-01

    The heart is a muscle with high energy demands. Hence, most patients with mitochondrial disease produced by defects in the oxidative phosphorylation (OXPHOS) system are susceptible to cardiac involvement. The presentation of mitochondrial cardiomyopathy includes hypertrophic, dilated and left ventricular noncompaction, but the molecular mechanisms involved in cardiac impairment are unknown. One of the most frequent OXPHOS defects in humans frequently associated with cardiomyopathy is cytochrome c oxidase (COX) deficiency caused by mutations in COX assembly factors such as Sco1 and Sco2. To investigate the molecular mechanisms that underlie the cardiomyopathy associated with Sco deficiency, we have heart specifically interfered scox expression, the single Drosophila Sco orthologue. Cardiac-specific knockdown of scox reduces fly lifespan, and it severely compromises heart function and structure, producing dilated cardiomyopathy. Cardiomyocytes with low levels of scox have a significant reduction in COX activity and they undergo a metabolic switch from OXPHOS to glycolysis, mimicking the clinical features found in patients harbouring Sco mutations. The major cardiac defects observed are produced by a significant increase in apoptosis, which is dp53-dependent. Genetic and molecular evidence strongly suggest that dp53 is directly involved in the development of the cardiomyopathy induced by scox deficiency. Remarkably, apoptosis is enhanced in the muscle and liver of Sco2 knock-out mice, clearly suggesting that cell death is a key feature of the COX deficiencies produced by mutations in Sco genes in humans.

  10. Diverse Phenotypic Expression of Cardiomyopathies in a Family with TNNI3 p.Arg145Trp Mutation

    PubMed Central

    Hwang, Ji-won; Jang, Mi-Ae; Jang, Shin Yi; Seo, Soo Hyun; Seong, Moon-Woo; Park, Sung Sup; Ki, Chang-Seok

    2017-01-01

    Genetic diagnosis of cardiomyopathies is challenging, due to the marked genetic and allelic heterogeneity and the lack of knowledge of the mutations that lead to clinical phenotypes. Here, we present the case of a large family, in which a single TNNI3 mutation caused variable phenotypic expression, ranging from restrictive cardiomyopathy (RCMP) to hypertrophic cardiomyopathy (HCMP) to near-normal phenotype. The proband was a 57-year-old female with HCMP. Examining the family history revealed that her elder sister had expired due to severe RCMP. Using a next-generation sequencing-based gene panel to analyze the proband, we identified a known TNNI3 gene mutation, c.433C>T, which is predicted to cause an amino acid substitution (p.Arg145Trp) in the highly conserved inhibitory region of the cardiac troponin I protein. Sanger sequencing confirmed that six relatives with RCMP or near-normal phenotypes also carried this mutation. To our knowledge, this is the first genetically confirmed family with diverse phenotypic expression of cardiomyopathies in Korea. Our findings demonstrate familial implications, where a single mutation in a sarcomere protein can cause diverse phenotypic expression of cardiomyopathies. PMID:28382084

  11. Takotsubo cardiomyopathy following subarachnoid haemorrhage.

    PubMed

    Maekawa, Hidetsugu; Hadeishi, Hiromu

    2014-08-01

    A 67-year-old woman was admitted with aneurysmal subarachnoid haemorrhage and a 12-lead ECG showed ST segment elevation. Transthoracic echocardiography confirmed akinesis of the left ventricular mid-apical segment, with an ejection fraction of 26%, features characteristic of takotsubo cardiomyopathy. Five days later, we identified thrombus in the apex of the left ventricle. Sixteen days after onset, the thrombus had disappeared and wall motion improved (ejection fraction 58%) without evidence of cardioembolism. Takotsubo cardiomyopathy is a cause of cardiac dysfunction after stroke, including SAH. It is characterised by transiently depressed contractile function of the left mid and apical ventricle, without obstructive coronary artery disease. Clinicians should suspect takotsubo cardiomyopathy in patients with subarachnoid haemorrhage who have an ECG abnormality. Echocardiography is needed to detect the distinctive regional wall motion abnormality. Despite its severity in the acute phase, takotsubo cardiomyopathy is self-limiting and its management is conservative.

  12. [Gastric adenomyoma clinically simulating hypertrophic pyloric stenosis].

    PubMed

    Sánchez García, S; Rubio Solís, D; Anes González, G; González Sánchez, S

    2016-01-01

    Gastric adenomyomas are extremely uncommon benign tumors in children. On histologic examination, these tumors have an epithelial component similar to pancreatic ducts. We present a case of a pyloric adenomyoma that clinically simulated hypertrophic pyloric stenosis in a newborn girl. Imaging tests, fundamentally magnetic resonance imaging, were very important in the characterization and diagnosis of this entity.

  13. Methamphetamine-Associated Cardiomyopathy

    PubMed Central

    Won, Sekon; Hong, Robert A.; Shohet, Ralph V.; Seto, Todd B.; Parikh, Nisha I.

    2015-01-01

    Methamphetamine and related compounds are now the second most commonly used illicit substance worldwide, after cannabis. Reports of methamphetamine-associated cardiomyopathy (MAC) are increasing, but MAC has not been well reviewed. This analysis of MAC will provide an overview of the pharmacology of methamphetamine, historical perspective and epidemiology, a review of case and clinical studies, and a summary of the proposed mechanisms for MAC. Clinically, many questions remain, including the appropriate therapeutic interventions for MAC, the incidence and prevalence of cardiac pathology in methamphetamine users, risk factors for developing MAC, and prognosis of these patients. In conclusion, recognition of the significance of MAC among physicians and other medical caregivers is important given the growing use of methamphetamine and related stimulants worldwide. PMID:24037954

  14. Genetics Home Reference: arrhythmogenic right ventricular cardiomyopathy

    MedlinePlus

    ... Genetics Home Health Conditions ARVC arrhythmogenic right ventricular cardiomyopathy Enable Javascript to view the expand/collapse boxes. ... Open All Close All Description Arrhythmogenic right ventricular cardiomyopathy ( ARVC ) is a form of heart disease that ...

  15. Cerebral embolic stroke after disappearing takotsubo cardiomyopathy.

    PubMed

    Matsuzono, Kosuke; Ikeda, Yoshio; Deguchi, Shoko; Yamashita, Toru; Kurata, Tomoko; Deguchi, Kentaro; Abe, Koji

    2013-11-01

    Takotsubo cardiomyopathy can induce cerebral embolic stroke because of intracardiac thrombosis, but the timing of cardiogenic embolism relating to takotsubo cardiomyopathy has not been well described. We evaluated a 71-year-old woman with takotsubo cardiomyopathy, who developed cardiogenic cerebral embolism after recovery of cardiac wall motion. Nevertheless, we treated her with anticoagulation therapy. The present clinical observation suggests that attention should be paid to the timing when takotsubo cardiomyopathy resolves against risk of cardiogenic cerebral embolism.

  16. PSORIASIS AND CARDIOMYOPATHY: AN INTRIGUING ASSOCIATION

    PubMed Central

    Prakash, Anupam; Deepshikha

    2010-01-01

    A 25-year-old male symptomatic of heart disease for four months presented with biventricular failure. Echocardiography revealed dilated cardiomyopathy. He had skin lesions for 10 years which were clinically and histopathologically identified as psoriasis. Association of cardiomyopathy with psoriasis is uncommon and intriguing. The link between dilated cardiomyopathy and psoriasis on a common inflammatory background is discussed. PMID:21063523

  17. Takotsubo cardiomyopathy triggered by alcohol withdrawal.

    PubMed

    Alexandre, Joakim; Benouda, Leila; Champ-Rigot, Laure; Labombarda, Fabien

    2011-07-01

    Takotsubo cardiomyopathy is a reversible cardiomyopathy frequently precipitated by a sudden emotional or physical stress. The exact physiopathology is still debated and may involve catecholamine-induced myocardial stunning. Alcohol withdrawal is associated with an hyperadrenergic state and may be a period at risk of cardiac events. We report a 56-year-old man with Takotsubo cardiomyopathy triggered by alcohol withdrawal.

  18. Biventricular Takotsubo cardiomyopathy in Graves hyperthyroidism.

    PubMed

    Perkins, Matthew J; Schachter, David T

    2014-03-01

    Graves hyperthyroidism is commonly seen in clinical practice and Takotsubo stress cardiomyopathy is an increasingly recognized cardiac complication of physical or emotional stress. We report the rare case of a patient with Graves hyperthyroidism that was complicated by severe biventricular takotsubo cardiomyopathy, which was demonstrated on heart catheterization. After appropriate pharmacologic treatment of her hyperthyroidism, she had complete resolution of her cardiomyopathy.

  19. Peripartum cardiomyopathy and dilated cardiomyopathy: different at heart

    PubMed Central

    Bollen, Ilse A. E.; Van Deel, Elza D.; Kuster, Diederik W. D.; Van Der Velden, Jolanda

    2015-01-01

    Peripartum cardiomyopathy (PPCM) is a severe cardiac disease occurring in the last month of pregnancy or in the first 5 months after delivery and shows many similar clinical characteristics as dilated cardiomyopathy (DCM) such as ventricle dilation and systolic dysfunction. While PPCM was believed to be DCM triggered by pregnancy, more and more studies show important differences between these diseases. While it is likely they share part of their pathogenesis such as increased oxidative stress and an impaired microvasculature, discrepancies seen in disease progression and outcome indicate there must be differences in pathogenesis as well. In this review, we compared studies in DCM and PPCM to search for overlapping and deviating disease etiology, pathogenesis and outcome in order to understand why these cardiomyopathies share similar clinical features but have different underlying pathologies. PMID:25642195

  20. Scar contractures, hypertrophic scars, and keloids.

    PubMed

    Brissett, A E; Sherris, D A

    2001-11-01

    A scar contracture is the result of a contractile wound-healing process occurring in a scar that has already been reepithelialized and adequately healed. Keloids and hypertrophic scars (HTSs) are fibrous tissue outgrowths that result from a derailment in the normal wound-healing process. The exact incidence of keloids and HTSs remains unknown. Beyond the common belief that trauma is the initiating event of keloid and hypertrophic scar formation, the remainder of the process remains uncertain. A combination of biochemical factors, skin tension, endocrinologic factors, and genetic factors are the likely culprits. Treatment begins by educating the patient about the etiology of the scarring process. All treatment protocols are individualized, but the standard approach to keloids and HTSs begins with corticosteroid injection followed by surgical excision, pressure dressings, and long-term follow-up.

  1. Calcification of in vitro developed hypertrophic cartilage

    SciTech Connect

    Tacchetti, C.; Quarto, R.; Campanile, G.; Cancedda, R.

    1989-04-01

    We have recently reported that dedifferentiated cells derived from stage 28-30 chick embryo tibiae, when transferred in suspension culture in the presence of ascorbic acid, develop in a tissue closely resembling hypertrophic cartilage. Ultrastructural examination of this in vitro formed cartilage showed numerous matrix vesicles associated with the extracellular matrix. In the present article we report that the in vitro developed hypertrophic cartilage undergoes calcification. We indicate a correlation between the levels of alkaline phosphatase activity and calcium deposition at different times of development. Following the transfer of cells into suspension culture and an initial lag phase, the level of alkaline phosphatase activity rapidly increased. In most experiments the maximum of activity was reached after 5 days of culture. When alkaline phosphatase activity and /sup 45/Ca deposition were measured in the same experiment, we observed that the increase in alkaline phosphatase preceded the deposition of nonwashable calcium deposits in the cartilage.

  2. Discoveries in peripartum cardiomyopathy.

    PubMed

    Fett, James D; Markham, David W

    2015-07-01

    The past decade has seen remarkable gains for outcomes in peripartum cardiomyopathy (PPCM), one of the leading causes of maternal mortality and morbidity in the USA and many other countries, including the high-incidence areas of Haiti and South Africa. This review article emphasizes the importance of continuing the process of increasing awareness of PPCM and presents details of this evolving picture, including important discoveries that point the way to full recovery for almost all PPCM subjects. In addition, new interventions will be highlighted, which may facilitate recovery. Numerous studies have demonstrated that when the diagnosis of PPCM is made with LVEF > 0.30, the probability is that recovery to LVEF ≥ 0.50 will occur in the overwhelming majority of subjects. PPCM patients diagnosed with severely depressed systolic function (LVEF < 0.30) and a remodeled left ventricle with greater dilatation (LVEDd ≥ 60mm) are least likely to reach the outcome recovery goals. These are the patients with the greatest need for newer interventional strategies.

  3. An update on peripartum cardiomyopathy.

    PubMed

    Dalzell, Jonathan R; Jackson, Colette E; Gardner, Roy S

    2011-09-01

    Peripartum cardiomyopathy is a rare but potentially devastating complication of pregnancy. Although the definition of this condition has recently been revised by the Heart Failure Association of the European Society of Cardiology, the pathogenesis of peripartum cardiomyopathy is not well understood and relatively little is known about its incidence and prevalence. Hence, peripartum cardiomyopathy is often under-recognized in the clinical setting. A heightened awareness of this condition and its current management options is therefore warranted throughout primary and secondary care. The identification of the putative role of prolactin in the development and progression of this condition has been recently discovered, with preclinical work suggesting beneficial effects of prolactin antagonism. In this article, we review the literature regarding this condition including these recent advances.

  4. Post-mortem genetic testing in a family with long-QT syndrome and hypertrophic cardiomyopathy.

    PubMed

    Kane, David A; Triedman, John

    2014-01-01

    Pediatric sudden unexplained deaths are rare and tragic events that should be evaluated with all the tools available to the medical community. The current state of genetic testing is an excellent resource that improves our ability to diagnose cardiovascular disorders that can lead to sudden cardiac arrest. Post-mortem genetic testing is not typically a covered benefit of health insurance and may not be offered to families in the setting of a negative autopsy. This unusual case includes two separate cardiovascular disorders that highlight the use of genetic testing and its role in diagnosis, screening, and risk stratification. The insurance company's decision to cover post-mortem testing demonstrated both compassion as well as an understanding of the long-term cost effectiveness.

  5. [Relationship between the level of maternal glycated hemoglobin and fetal hypertrophic cardiomyopathy].

    PubMed

    Sánchez-Martínez, Karla Lucía; Oseguera-Torres, Luis Fernando; Ávalos-Nuño, Joel

    2016-01-01

    Introducción: la diabetes mellitus constituye la alteración metabólica más frecuentemente asociada al embarazo. A medida que se optimiza el manejo de la diabetes durante la gestación, disminuye la frecuencia y severidad de las complicaciones fetales y neonatales. El objetivo de este trabajo fue identificar la relación que existe entre el nivel de hemoglobina glucosilada materna y la cardiomiopatía hipertrófica fetal. Métodos: estudio transversal analítico de julio a noviembre del 2015. Se incluyeron pacientes con embarazo simple de las 28-37 semanas con diagnóstico de diabetes mellitus pregestacional o gestacional. Se les realizó un ecocardiograma fetal, asimismo se les efectuó la medición de hemoglobina glucosilada. Resultados: se incluyeron 104 pacientes embarazadas diabéticas en el estudio, 83 pacientes en el grupo con hemoglobina glucosilada normal y 21 con hemoglobina glucosilada alterada. De las 104 pacientes, 12 presentaron cardiomiopatía hipertrófica fetal; 5 del grupo con hemoglobina glucosilada normal y 7 del grupo con hemoglobina glucosilada alterada. Se identificó que existe una clara asociación reportada previamente entre el grado de descontrol metabólico materno y la presencia de complicaciones fetales y neonatales. Conclusiones: se observó una correlación positiva entre los valores de hemoglobina glucosilada materna elevada y el aumento del grosor del septum interventricular fetal. La evaluación ecocardiográfica fetal es recomendada en todas las embarazadas con diabetes mellitus gestacional y pregestacional.

  6. Percutaneous cardioscopy of the cardiac chambers in patients with hypertrophic cardiomyopathy

    NASA Astrophysics Data System (ADS)

    Fujimori, Yoshiharu; Uchida, Yasumi; Nakamura, Fumitaka; Tomaru, Takanobu; Miwa, Atsuko; Hirose, Junichi; Sasaki, Michihiko; Oshima, Tomomitsu; Tsubouchi, Hiroyuki

    1993-05-01

    Recent advances in fiberoptic technology enables us to observe the cardiac chambers percutaneously in various categories of heart disease. We applied cardioscopy in 4 patients with HCM. Two of them presented excessive or good left ventricular function and no history of congestive heart failure (CHF). The other two patients showed reduced left ventricular function with a history of CHF. Cardioscopy was successfully performed in all patients. In patients with excessive or good left ventricular function, the color of the endocardial surface was light brown mixed with white. The trabeculae were significantly thick and contracted vigorously. In patients with reduced left ventricular function, the color was whiter, and the thickness and contraction of the trabeculae were reduced obviously. Myocardial biopsy revealed that interstitial fibrosis was prominent in the latters. These results indicate that (1) cardioscopy is safe and useful for evaluation of the internal surface of the ventricle in patients with HCM, and (2) cardioscopic characteristics of the ventricle are closely related to histopathological features.

  7. Inflammation and cutaneous nervous system involvement in hypertrophic scarring

    PubMed Central

    Li, Shao-hua; Yang, Heng-lian; Xiao, Hu; Wang, Yi-bing; Wang, De-chang; Huo, Ran

    2015-01-01

    This study aimed to use a mouse model of hypertrophic scarring by mechanical loading on the dorsum of mice to determine whether the nervous system of the skin and inflammation participates in hypertrophic scarring. Results of hematoxylin-eosin and immunohistochemical staining demonstrated that inflammation contributed to the formation of a hypertrophic scar and increased the nerve density in scar tissue.Western blot assay verified that interleukin-13 expression was increased in scar tissue. These findings suggest that inflammation and the cutaneous nervous system play a role in hypertrophic scar formation. PMID:26692869

  8. Peripartum cardiomyopathy: a contemporary review.

    PubMed

    Shah, Tina; Ather, Sameer; Bavishi, Chirag; Bambhroliya, Arvind; Ma, Tony; Bozkurt, Biykem

    2013-01-01

    Peripartum cardiomyopathy is a rare and potentially fatal disease. Though approximately half of the patients recover, the clinical course is highly variable and some patients develop refractory heart failure and persistent left ventricular systolic dysfunction. It is diagnosed when women present with heart failure secondary to left ventricular systolic dysfunction towards the end of pregnancy or in the months following delivery, where no other cause of heart failure is found. Etiology remains unclear, and treatment is similar to other cardiomyopathies and includes evidence-based standard heart failure management strategies. Experimental strategies such as intravenous immunoglobulin and bromocriptine await further clinical validation.

  9. MicroRNAs as therapeutic targets in cardiomyopathies: myth or reality?

    PubMed

    Nair, Nandini; Gongora, Enrique

    2014-12-01

    The identification of biomarkers for cardiomyopathy presents a distinct challenge as the etiologies are widely varied. The discovery of small non-coding miRNAs with gene regulatory function has opened new avenues of investigation in basic and clinical sciences. The search for regulatory nucleotide sequences that have specific gene targets have put miRNAs at the forefront of development of therapeutics, and may serve as valuable diagnostic and/or therapeutic targets. MiRNAs appear to influence both positive and negative remodeling. As cardiac remodeling is a complex process, global molecular networks and miRNA profiles may be required to fulfill the roles of macroregulators. The type of cardiomyopathy leading to heart failure in the long run appears to have a distinct molecular pattern underlying the pathophysiology. This review discusses in brief the existing literature on the molecular signatures in dilated, ischemic, hypertrophic, stress, and peripartum cardiomyopathies that may be used to target therapies for specific etiologies once diagnosed, therefore exploring the utility of specific miRNAs in tailoring therapy for heart failure based on etiology.

  10. Ablation of the Cardiac-Specific Gene Leucine-Rich Repeat Containing 10 (Lrrc10) Results in Dilated Cardiomyopathy

    PubMed Central

    Brody, Matthew J.; Hacker, Timothy A.; Patel, Jitandrakumar R.; Feng, Li; Sadoshima, Junichi; Tevosian, Sergei G.; Balijepalli, Ravi C.; Moss, Richard L.; Lee, Youngsook

    2012-01-01

    Leucine-rich repeat containing 10 (LRRC10) is a cardiac-specific protein exclusively expressed in embryonic and adult cardiomyocytes. However, the role of LRRC10 in mammalian cardiac physiology remains unknown. To determine if LRRC10 is critical for cardiac function, Lrrc10-null (Lrrc10−/−) mice were analyzed. Lrrc10−/− mice exhibit prenatal systolic dysfunction and dilated cardiomyopathy in postnatal life. Importantly, Lrrc10−/− mice have diminished cardiac performance in utero, prior to ventricular dilation observed in young adults. We demonstrate that LRRC10 endogenously interacts with α-actinin and α-actin in the heart and all actin isoforms in vitro. Gene expression profiling of embryonic Lrrc10−/− hearts identified pathways and transcripts involved in regulation of the actin cytoskeleton to be significantly upregulated, implicating dysregulation of the actin cytoskeleton as an early defective molecular signal in the absence of LRRC10. In contrast, microarray analyses of adult Lrrc10−/− hearts identified upregulation of oxidative phosphorylation and cardiac muscle contraction pathways during the progression of dilated cardiomyopathy. Analyses of hypertrophic signal transduction pathways indicate increased active forms of Akt and PKCε in adult Lrrc10−/− hearts. Taken together, our data demonstrate that LRRC10 is essential for proper mammalian cardiac function. We identify Lrrc10 as a novel dilated cardiomyopathy candidate gene and the Lrrc10−/− mouse model as a unique system to investigate pediatric cardiomyopathy. PMID:23236519

  11. Recent advances in cirrhotic cardiomyopathy.

    PubMed

    Karagiannakis, Dimitrios S; Papatheodoridis, George; Vlachogiannakos, Jiannis

    2015-05-01

    Cirrhotic cardiomyopathy, a cardiac dysfunction presented in patients with cirrhosis, represents a recently recognized clinical entity. It is characterized by altered diastolic relaxation, impaired contractility, and electrophysiological abnormalities, in particular prolongation of the QT interval. Several mechanisms seem to be involved in the pathogenesis of cirrhotic cardiomyopathy, including impaired function of beta-receptors, altered transmembrane currents, and overproduction of cardiodepressant factors, like nitric oxide, tumor necrosis factor α, and endogenous cannabinoids. Diastolic dysfunction is the first manifestation of cirrhotic cardiomyopathy and reflects the increased stiffness of the cardiac mass, which leads to delayed left ventricular filling. On the other hand, systolic incompetence is presented later, is usually unmasked during pharmacological or physical stress, and predisposes to the development of hepatorenal syndrome. The prolongation of QT is found in about 50 % of cirrhotic patients, but rarely leads to fatal arrhythmias. Cirrhotics with blunted cardiac function seem to have poorer survival rates compared to those without, and the risk is particularly increased during the insertion of transjugular intrahepatic portosystemic shunt or liver transplantation. Till now, there is no specific treatment for the management of cirrhotic cardiomyopathy. New agents, targeting to its pathogenetical mechanisms, may play some role as future therapeutic options.

  12. Periostin induces fibroblast proliferation and myofibroblast persistence in hypertrophic scarring.

    PubMed

    Crawford, Justin; Nygard, Karen; Gan, Bing Siang; O'Gorman, David Brian

    2015-02-01

    Hypertrophic scarring is characterized by the excessive development and persistence of myofibroblasts. These cells contract the surrounding extracellular matrix resulting in the increased tissue density characteristic of scar tissue. Periostin is a matricellular protein that is abnormally abundant in fibrotic dermis, however, its roles in hypertrophic scarring are largely unknown. In this report, we assessed the ability of matrix-associated periostin to promote the proliferation and myofibroblast differentiation of dermal fibroblasts isolated from the dermis of hypertrophic scars or healthy skin. Supplementation of a thin type-I collagen cell culture substrate with recombinant periostin induced a significant increase in the proliferation of hypertrophic scar fibroblasts but not normal dermal fibroblasts. Periostin induced significant increases in supermature focal adhesion formation, α smooth muscle actin levels and collagen contraction in fibroblasts cultured from hypertrophic scars under conditions of increased matrix tension in three-dimensional type-I collagen lattices. Inhibition of Rho-associated protein kinase activity significantly attenuated the effects of matrix-associated periostin on hypertrophic scar fibroblasts and myofibroblasts. Depletion of endogenous periostin expression in hypertrophic scar myofibroblasts resulted in a sustained decrease in α smooth muscle actin levels under conditions of reducing matrix tension, while matrix-associated periostin levels caused the cells to retain high levels of a smooth muscle actin under these conditions. These findings indicate that periostin promotes Rho-associated protein kinase-dependent proliferation and myofibroblast persistence of hypertrophic scar fibroblasts and implicate periostin as a potential therapeutic target to enhance the resolution of scars.

  13. Tissue Doppler imaging for detection of radial and longitudinal myocardial dysfunction in a family of cats affected by dystrophin-deficient hypertrophic muscular dystrophy.

    PubMed

    Chetboul, Valérie; Blot, Stephane; Sampedrano, Carolina Carlos; Thibaud, Jean-Laurent; Granger, Nicolas; Tissier, Renaud; Bruneval, Patrick; Gaschen, Frederic; Gouni, Vassiliki; Nicolle, Audrey P; Pouchelon, Jean-Louis

    2006-01-01

    Diagnosis of feline hypertrophic cardiomyopathy currently is based on the presence of myocardial hypertrophy detected using conventional echocardiography. The accuracy of tissue Doppler imaging (TDI) for earlier detection of the disease has never been described. The objective of this sudy was to quantify left ventricular free wall (LVFW) velocities in cats with hypertrophic muscular dystrophy (HFMD) during preclinical cardiomyopathy using TDI. The study animals included 22 healthy controls and 7 cats belonging to a family of cats with HFMD (2 affected adult males, 2 heterozygous adult females, one 2.5-month-old affected male kitten, and 2 phenotypically normal female kittens from the same litter). All cats were examined via conventional echocardiography and 2-dimensional color TDI. No LVFW hypertrophy was detected in the 2 carriers or in the affected kitten when using conventional echocardiography and histologic examination, respectively. The LVFW also was normal for 1 affected male and at the upper limit of normal for the 2nd male. Conversely, LVFW dysfunction was detected in all affected and carrier cats with HFMD when using TDI. TDI consistently detects LVFW dysfunction in cats with HFMD despite the absence of myocardial hypertrophy. Therefore, TDI appears more sensitive than conventional echocardiography in detecting regional myocardial abnormalities.

  14. Blepharoptosis and hypertrophic osteoarthropathy: A case report

    PubMed Central

    Doğan, Aysun Şanal; Acaroğlu, Gölge; Dikmetas, Ozlem

    2016-01-01

    A 52-year-old male patient presented to our hospital with a history of secondary hypertrophic osteoarthropathy (HOA) associated with an abdominal neoplasia and blepharoptosis. He had finger clubbing, hyperhidrosis, and hypertrichosis. He also had a recent history of extensive abdominal surgery with a pathology report of myelolipoma. Routine blood work was unremarkable. Upper eyelid reconstruction with blepharoplasty, upper eyelid wedge resection, and brow suspension was performed to address his eyelid concerns. By this case report, we would like to attract notice that the eyelid involvement may be a part of HOA and to emphasize the importance of systemic and pathologic evaluation in failed blepharoptosis surgery. PMID:27221686

  15. Factors associated with infantile hypertrophic pyloric stenosis.

    PubMed

    Jedd, M B; Melton, L J; Griffin, M R; Kaufman, B; Hoffman, A D; Broughton, D; O'Brien, P C

    1988-03-01

    We examined perinatal factors in relation to the rise in incidence of infantile hypertrophic pyloric stenosis among children in Olmsted County, Minnesota, during the period from 1950 through 1984. Primogeniture was associated with male infants but not female infants; some factor related to primogeniture, such as breast-feeding, may be etiologically important. Our data did not support a role for maternal disease, use of doxylamine succinate-pyridoxide hydrochloride (Bendectin), or an infectious process. Further study should be directed toward environmental factors associated with primogeniture.

  16. Heart failure and tachycardia-induced cardiomyopathy.

    PubMed

    Ellis, Ethan R; Josephson, Mark E

    2013-12-01

    Congestive heart failure is a major health care concern affecting almost six million Americans and an estimated 23 million people worldwide, and its prevalence is increasing with time. Long-standing tachycardia is a well-recognized cause of heart failure and left ventricular dysfunction and has led to the nomenclature, tachycardia-induced cardiomyopathy. Tachycardia-induced cardiomyopathy is generally a reversible cardiomyopathy with effective treatment of the causative arrhythmia, either with medications, surgery, or catheter ablation. Tachycardia-induced cardiomyopathy remains poorly understood and is likely under-diagnosed. A better understanding of tachycardia-induced cardiomyopathy and improved recognition of its presence in clinical practice is vital to the health of patients with this disorder. The goal of this review is to discuss the pathogenesis and clinical manifestations of tachycardia-induced cardiomyopathy, as well as approaches to its diagnosis and treatment.

  17. Genetic engineering and therapy for inherited and acquired cardiomyopathies.

    PubMed

    Day, Sharlene; Davis, Jennifer; Westfall, Margaret; Metzger, Joseph

    2006-10-01

    The cardiac myofilaments consist of a highly ordered assembly of proteins that collectively generate force in a calcium-dependent manner. Defects in myofilament function and its regulation have been implicated in various forms of acquired and inherited human heart disease. For example, during cardiac ischemia, cardiac myocyte contractile performance is dramatically downregulated due in part to a reduced sensitivity of the myofilaments to calcium under acidic pH conditions. Over the last several years, the thin filament regulatory protein, troponin I, has been identified as an important mediator of this response. Mutations in troponin I and other sarcomere genes are also linked to several distinct inherited cardiomyopathic phenotypes, including hypertrophic, dilated, and restrictive cardiomyopathies. With the cardiac sarcomere emerging as a central player for such a diverse array of human heart diseases, genetic-based strategies that target the myofilament will likely have broad therapeutic potential. The development of safe vector systems for efficient gene delivery will be a critical hurdle to overcome before these types of therapies can be successfully applied. Nonetheless, studies focusing on the principles of acute genetic engineering of the sarcomere hold value as they lay the essential foundation on which to build potential gene-based therapies for heart disease.

  18. Tachycardia-induced cardiomyopathy in pregnancy.

    PubMed

    Joseph, Anil C; Prapa, Matina; Pellicori, Pierpaolo; Mabote, Thato; Nasir, Mansoor; Clark, Andrew L

    2016-10-01

    Heart failure in pregnancy is rare, but usually ascribed to peripartum cardiomyopathy in the absence of other possible diagnoses. However, heart failure can develop solely due to a tachycardia, so-called 'tachycardia-induced cardiomyopathy'. The incidence of tachycardia-induced cardiomyopathy in pregnancy is unknown, but it is a treatable and potentially reversible cause of heart failure. Clinically, tachycardia-induced cardiomyopathy during pregnancy might present in a similar manner, but its management has to be individualized according to the arrhythmic substrate and usually involve multidisciplinary input from specialists in obstetrics, cardiac electrophysiology and heart failure.

  19. Genetic basis of dilated cardiomyopathy.

    PubMed

    Pérez-Serra, Alexandra; Toro, Rocio; Sarquella-Brugada, Georgia; de Gonzalo-Calvo, David; Cesar, Sergi; Carro, Esther; Llorente-Cortes, Vicenta; Iglesias, Anna; Brugada, Josep; Brugada, Ramon; Campuzano, Oscar

    2016-12-01

    Dilated cardiomyopathy is a rare cardiac disease characterized by left ventricular dilatation and systolic dysfunction leading to heart failure and sudden cardiac death. Currently, despite several conditions have been reported as aetiologies of the disease, a large number of cases remain classified as idiopathic. Recent studies determine that nearly 60% of cases are inherited, therefore due to a genetic cause. Progressive technological advances in genetic analysis have identified over 60 genes associated with this entity, being TTN the main gene, so far. All these genes encode a wide variety of myocyte proteins, mainly sarcomeric and desmosomal, but physiopathologic pathways are not yet completely unraveled. We review the recent published data about genetics of familial dilated cardiomyopathy.

  20. Peripartum Cardiomyopathy Presenting as Bradycardia

    PubMed Central

    Rose, Carl H.; Tweet, Marysia S.; Hayes, Sharonne N.; Best, Patricia J. M.; Blauwet, Lori A.

    2017-01-01

    Peripartum cardiomyopathy (PPCM) is a disease that typically affects young otherwise healthy women. As PPCM is associated with significant mortality, timely diagnosis is necessary to ensure appropriate care. To our knowledge, this represents the first reported case of PPCM presenting as symptomatic bradycardia. We describe the patient's clinical presentation and relevant findings and review the potential etiology and ramifications of bradycardia in patients with PPCM. PMID:28255481

  1. Cardiomyopathies and the Armed Forces.

    PubMed

    Holdsworth, D A; Cox, A T; Boos, C; Hardman, R; Sharma, S

    2015-09-01

    Cardiomyopathies are a group of heterogeneous myocardial diseases that are frequently inherited and are a recognised cause of premature sudden cardiac death in young individuals. Incomplete expressions of disease and the overlap with the physiological cardiac manifestations of regular intensive exercise create diagnostic challenges in young athletes and military recruits. Early identification is important because sudden death in the absence of prodromal symptoms is a common presentation, and there are several therapeutic strategies to minimise this risk. This paper examines the classification and clinical features of cardiomyopathies with specific reference to a military population and provides a detailed account of the optimum strategy for diagnosis, indications for specialist referral and specific guidance on the occupational significance of cardiomyopathy. A 27-year-old Lance Corporal Signaller presents to his Regimental medical officer (RMO) after feeling 'light-headed' following an 8 mile unloaded run. While waiting to see the RMO, the medical sergeant records a 12-lead ECG. The ECG is reviewed by the RMO immediately prior to the consultation and shows voltage criteria for left ventricular (LV) hypertrophy and inverted T-waves in II, III, aVF and V1-V3 (Figure 1). This Lance Corporal is a unit physical training instructor and engages in >10 h of aerobic exercise per week. He is a non-smoker and does not have any significant medical history.

  2. Research priorities in sarcomeric cardiomyopathies.

    PubMed

    van der Velden, Jolanda; Ho, Carolyn Y; Tardiff, Jil C; Olivotto, Iacopo; Knollmann, Bjorn C; Carrier, Lucie

    2015-04-01

    The clinical variability in patients with sarcomeric cardiomyopathies is striking: a mutation causes cardiomyopathy in one individual, while the identical mutation is harmless in a family member. Moreover, the clinical phenotype varies ranging from asymmetric hypertrophy to severe dilatation of the heart. Identification of a single phenotype-associated disease mechanism would facilitate the design of targeted treatments for patient groups with different clinical phenotypes. However, evidence from both the clinic and basic knowledge of functional and structural properties of the sarcomere argues against a 'one size fits all' therapy for treatment of one clinical phenotype. Meticulous clinical and basic studies are needed to unravel the initial and progressive changes initiated by sarcomere mutations to better understand why mutations in the same gene can lead to such opposing phenotypes. Ultimately, we need to design an 'integrative physiology' approach to fully realize patient/gene-tailored therapy. Expertise within different research fields (cardiology, genetics, cellular biology, physiology, and pharmacology) must be joined to link longitudinal clinical studies with mechanistic insights obtained from molecular and functional studies in novel cardiac muscle systems. New animal models, which reflect both initial and more advanced stages of sarcomeric cardiomyopathy, will also aid in achieving these goals. Here, we discuss current priorities in clinical and preclinical investigation aimed at increasing our understanding of pathophysiological mechanisms leading from mutation to disease. Such information will provide the basis to improve risk stratification and to develop therapies to prevent/rescue cardiac dysfunction and remodelling caused by sarcomere mutations.

  3. Determinants of Thyrotoxic Cardiomyopathy Recovery

    PubMed Central

    Oliveros-Ruiz, Lucia; Vallejo, Maite; Diez Canseco, L. Fernando; Cárdenas, Manuel; Hermosillo, J. Antonio G.

    2013-01-01

    The purpose was to evaluate the effect of the disease duration prior to treatment, thyroid hormones level, or both on the reversibility of dilated cardiomyopathy. Between January 2006 and December 2010, a longitudinal study with a 6 months follow-up was carried on. One hundred and seventy patients with hyperthyroidism were referred to the cardiologist, and 127 had a 6 months followup after antithyroid treatment and were evaluated by echocardiography. Dilated cardiomyopathy reversibility criteria were established according to echocardiographic parameters. Complete reversibility existed when all parameters were met, partial reversibility when LVEF was ≥55% plus two or three other parameters, and no reversibility when LVEF was ≤55% regardless of other parameters. The results showed that echocardiography parameters related to the regression of myocardial mass were associated with a disease duration shorter than 10.38 months. This was the main predictive variable for reversal of dilated cardiomyopathy, followed by β-blocker treatment, and the last predictive variable was the serum level of free triiodothyronine. This study showed that the effect on the myocardium related to thyrotoxicosis was associated with the disease duration before treatment. PMID:24106705

  4. Pregnancy in inherited and acquired cardiomyopathies.

    PubMed

    Herrey, Anna S

    2014-05-01

    Cardiomyopathy encompasses a wide spectrum of heart muscle disease, which can have an impact on the patient's ability to sustain the increased cardiac workload of pregnancy. Pregnancy can also unmask previously unknown cardiomyopathy. The outcome for both mother and baby is often related to the patient's functional class prior to pregnancy, and a multidisciplinary approach to managing this challenging group of patients is pivotal.

  5. Recurrent takotsubo cardiomyopathy in a child.

    PubMed

    Srivastava, Nayan T; Parent, John J; Hurwitz, Roger A

    2016-02-01

    Takotsubo cardiomyopathy or transient apical ballooning syndrome very rarely presents in children. In all patients with takotsubo, it is estimated that only 3.5% will have recurrence. In this study, we describe a case of recurrent takotsubo cardiomyopathy in a child, likely triggered by status epilepticus.

  6. Arrhythmogenic right ventricular cardiomyopathy in a weimaraner

    PubMed Central

    Eason, Bryan D.; Leach, Stacey B.; Kuroki, Keiichi

    2015-01-01

    Arrhythmogenic right ventricular cardiomyopathy (ARVC) was diagnosed postmortem in a weimaraner dog. Syncope, ventricular arrhythmias, and sudden death in this patient combined with the histopathological fatty tissue infiltration affecting the right ventricular myocardium are consistent with previous reports of ARVC in non-boxer dogs. Arrhythmogenic right ventricular cardiomyopathy has not been previously reported in weimaraners. PMID:26483577

  7. Idiopathic hypertrophic spinal pachymeningitis: a case report.

    PubMed Central

    Park, S. H.; Whang, C. J.; Sohn, M.; Oh, Y. C.; Lee, C. H.; Whang, Y. J.

    2001-01-01

    Idiopathic hypertrophic pachymeningitis (IHP) is a rare, chronic nonspecific and granulomatous inflammatory disorder of the dura with unknown etiology. The diagnosis can be established by open biopsy and exclusion of all other specific granulomatous and infectious diseases. We report a typical case of spinal IHP occurring in a long segment of cervical and thoracic dura from C6 to T8. The patient was 56-yr-old female, who had been suffered from pain on her upper back and both arms for 3 months and recent onset motor weakness of both legs. During the 9 months of follow-up period, she experienced the improvement of her neurologic symptoms with combined therapy of partial excision and corticosteroid medication. Since early surgical intervention and subsequent pulse steroid therapy are mandatory for this disease to avoid irreversible damage of nervous system, the identification of this unique disease entity is essential on frozen diagnosis. A few cases have been reported in Korean literature. PMID:11641545

  8. Hypertrophic gastropathy with transient sessile polyps.

    PubMed

    Pesce, F; Barabino, A; Dufour, C; Caffarena, P E; Callea, F; Gatti, R

    1992-04-01

    We report an 8-year-old boy with hypertrophic gastropathy (HG) associated with duodenal Giardia lamblia infestation. The follow-up was complicated by the development of gastric polyps at the site of previous biopsies that spontaneously disappeared within 15 months. Despite the histological similarity, the different course between Ménétrier's disease (MD) in adults (chronic, with frequent development of sessile or pedunculate polyps) and HG (uncomplicated and usually spontaneously resolving) suggests a different pathogenesis. Viral (cytomegalovirus) and bacterial (Helicobacter pylori) infections have been described in association with HG and they could play an important pathogenetic role. The term HG better defines the childhood disease in which a conservative management is recommended.

  9. Takotsubo Cardiomyopathy Associated with Severe Hypothyroidism in an Elderly Female

    PubMed Central

    Brenes-Salazar, Jorge A.

    2016-01-01

    Takotsubo cardiomyopathy, also known as stress cardiomyopathy, is a syndrome that affects predominantly postmenopausal women. Despite multiple described mechanisms, intense, neuroadrenergic myocardial stimulation appears to be the main trigger. Hyperthyroidism, but rarely hypothyroidism, has been described in association with Takotsubo cardiomyopathy. Herein, we present a case of stress cardiomyopathy in the setting of symptomatic hypothyroidism. PMID:27512537

  10. Herpes simplex virus-induced cardiomyopathy successfully treated with acyclovir.

    PubMed

    Kuchynka, Petr; Palecek, Tomas; Hrbackova, Hana; Vitkova, Ivana; Simek, Stanislav; Nemecek, Eduard; Aster, Viktor; Louch, William E; Aschermann, Michael; Linhart, Ales

    2010-10-01

    Inflammatory dilated cardiomyopathy (DCMi) represents an acquired form of dilated cardiomyopathy. Viral infection is the most common cause of DCMi. In contrast with other cardiotropic viruses, herpes simplex virus (HSV) is a very rare finding in endomyocardial biopsies of patients with dilated cardiomyopathy. We report a case of HSV-induced cardiomyopathy successfully treated with acyclovir.

  11. Nemaline myopathy with dilated cardiomyopathy in childhood.

    PubMed

    Gatayama, Ryohei; Ueno, Kentaro; Nakamura, Hideaki; Yanagi, Sadamitsu; Ueda, Hideaki; Yamagishi, Hiroyuki; Yasui, Seiyo

    2013-06-01

    We present a case of a 9-year-old boy with nemaline myopathy and dilated cardiomyopathy. The combination of nemaline myopathy and cardiomyopathy is rare, and this is the first reported case of dilated cardiomyopathy associated with childhood-onset nemaline myopathy. A novel mutation, p.W358C, in ACTA1 was detected in this patient. An unusual feature of this case was that the patient's cardiac failure developed during early childhood with no delay of gross motor milestones. The use of a β-blocker did not improve his clinical course, and the patient died 6 months after diagnosis of dilated cardiomyopathy. Congenital nonprogressive nemaline myopathy is not necessarily a benign disorder: deterioration can occur early in the course of dilated cardiomyopathy with neuromuscular disease, and careful clinical evaluation is therefore necessary.

  12. Epidermolysis Bullosa with Hypertrophic Pyloric Stenosis in a Newborn.

    PubMed

    Ben Dhaou, Mahdi; Ammar, Saloua; Louati, Hamdi; Zitouni, Hayet; Jallouli, Mohamed; Mhiri, Riadh

    2015-01-01

    Epidermolysis bullosa (EB) is an inherited blistering disorder characterized by the fragility of the skin and mucous membranes. Extracutaneous manifestations can be associated. We report a unique concomitant occurrence of EB and hypertrophic pyloric stenosis in a newborn.

  13. Epidermolysis Bullosa with Hypertrophic Pyloric Stenosis in a Newborn

    PubMed Central

    Ben Dhaou, Mahdi; Ammar, Saloua; Louati, Hamdi; Zitouni, Hayet; Jallouli, Mohamed; Mhiri, Riadh

    2015-01-01

    Epidermolysis bullosa (EB) is an inherited blistering disorder characterized by the fragility of the skin and mucous membranes. Extracutaneous manifestations can be associated. We report a unique concomitant occurrence of EB and hypertrophic pyloric stenosis in a newborn. PMID:26500857

  14. Management of scar contractures, hypertrophic scars, and keloids.

    PubMed

    Sherris, D A; Larrabee, W F; Murakami, C S

    1995-10-01

    Aberrant fibrous tissue formation after surgery or trauma still presents a challenge to surgeons. Current research hopes to identify the characteristics of the population of fibroblasts that lead to hypertrophic or keloid scar formation. Surgical procedures and laser therapy followed by intralesional steroid treatments still are the foundation of treatment; but new modalities are being applied. The pathogenesis and management of hypertrophic scars, keloids, and scar contractures are discussed in this article.

  15. Hypertrophic osteoarthropathy associated with Fallot's tetralogy—a case report

    PubMed Central

    George, B. Olu.; Mabayoje, J. Olu.

    1975-01-01

    A case of Fallot's tetralogy associated with hypertrophic osteoarthropathy in a young Nigerian female is described. The clinical spectrum of hypertrophic osteoarthropathy is reviewed. The rarity of this syndrome is stressed. Some other aspects of the clinical manifestation of cyanotic congenital heart disease which may mimic the skeletal syndrome are mentioned. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6 PMID:1197165

  16. Improving outcomes in peripartum cardiomyopathy.

    PubMed

    Dalzell, Jonathan R; Cannon, Jane A; Simpson, Joanne; Gardner, Roy S; Petrie, Mark C

    2015-06-01

    Peripartum cardiomyopathy (PPCM) is a rare condition with a diverse spectrum of potential outcomes, ranging from frequent complete recovery to fulminant heart failure and death. The pathogenesis of PPCM is not well understood, and relatively little is known about its incidence and prevalence. PPCM is often under-recognised in the clinical setting. Early investigation and diagnosis with subsequent expert management may improve outcomes. The development of registries will allow this condition to be better characterised and may help answer crucial questions regarding its optimal medical and surgical management. This paper reviews the potential approaches to improve outcomes in patients with PPCM.

  17. Induction of SENP1 in myocardium contributes to abnormities of mitochondria and cardiomyopathy.

    PubMed

    Cai, Rong; Gu, Jianmin; Sun, Haipeng; Liu, Xiaobing; Mei, Wenhan; Qi, Yitao; Xue, Song; Ren, Shuxun; Rabinowitz, Joseph E; Wang, Yibin; Yeh, Edward T H; Cheng, Jinke

    2015-02-01

    Defect in mitochondrial biogenesis and cardiac energy metabolism is a critical contributing factor to cardiac hypertrophy and heart failure. Sentrin/SUMO specific protease 1 (SENP1) mediated regulation of PGC-1α transcriptional activity plays an essential role in mitochondrial biogenesis and mitochondrial function. However, whether SENP1 plays a role in cardiac hypertrophy and failure is unknown. We investigated whether alteration in SENP1 expression affects cardiomyopathy and the underlying mechanism. In our present study, we found that the expression of SENP1 was induced in mouse and human failing hearts associated with induced expression of mitochondrial genes. SENP1 expression in cardiomyocytes was induced by hypertrophic stimuli through calcium/calcineurin-NFAT3. SENP1 regulated mitochondrial gene expression by de-SUMOylation of MEF-2C, which enhanced MEF-2C-mediated PGC-1α transcription. Genetic induction of SENP1 led to mitochondrial dysregulation and cardiac dysfunction in vivo. Our data showed that pathogenesis of cardiomyopathy is attributed by SENP1 mediated regulation of mitochondrial abnormities. SENP1 up-regulation in diseased heart is mediated via calcineurin-NFAT/MEF2C-PGC-1α pathway.

  18. Associations between 'valentine' heart shape, atrial enlargement and cardiomyopathy in cats.

    PubMed

    Winter, Matthew D; Giglio, Robson F; Berry, Clifford R; Reese, David J; Maisenbacher, Herbert W; Hernandez, Jorge A

    2015-06-01

    'Valentine' heart shape is a common qualifier used in veterinary radiology to describe a cardiac silhouette with focal enlargement at the level of the base of the heart in feline patients. Anecdotally, this sign has been thought to be related to biatrial enlargement and also to hypertrophic cardiomyopathy (HCM). However, to our knowledge, there has been no study performed to assess the association between cardiac chamber enlargement and cardiac disease with the 'valentine'-shaped heart. The aim of this study was to verify the association between the 'valentine' heart shape observed in ventrodorsal thoracic radiographs and the presence of singular or combined cardiac chamber enlargement, and also the presence and type of cardiomyopathy (CM) in cats. A search of the database of the Small Animal Veterinary Hospital of the University of Florida for cats with a radiology report of thoracic radiographs that contained the words 'valentine' and 'biatrial', and echocardiography performed within 1 week, was undertaken; 41 cases met the inclusion criteria. Eighty-two percent of the cats of the study sample had some form of CM. The 'valentine' heart shape was associated with biatrial enlargement in 41% of the patients in our study sample that had some form of CM and just 8% of cases diagnosed with HCM, suggesting that the 'valentine' heart shape has a low association with HCM or biatrial enlargement; however, it should be considered a sign of feline CM.

  19. Statin Induced Regression of Cardiomyopathy Trial: A Randomized, Placebo-controlled Double-blind Trial

    PubMed Central

    Hersi, Ahmad; Giannoccaro, J. Peter; Howarth, Andrew; Exner, Derek; Weeks, Sarah; Eitel, Ingo; Herman, R. Cameron; Duff, Henry; Ritchie, Debbie; Mcrae, Maureen; Sheldon, Robert

    2016-01-01

    Background: Hypertrophic cardiomyopathy (HCM), characterized by a thickened, fibrotic myocardium, remains the most common cause of sudden cardiac death in young adults. Based on animal and clinical data, we hypothesized that atorvastatin would induce left ventricular (LV) mass regression. Methods: Statin Induced Regression of Cardiomyopathy Trial (SIRCAT) was a randomized, placebo-controlled study. The primary endpoint was change in LV mass measured by cardiac magnetic resonance imaging 12 months after treatment with once-daily atorvastatin 80 mg or placebo. A key secondary endpoint was diastolic dysfunction measured echocardiographically by transmitral flow velocities. SIRCAT is registered with www.clinicaltrials.gov (NCT00317967). Results: Of 222 screened patients, 22 were randomized evenly to atorvastatin and placebo. The mean age was 47 ± 10 years, and 15 (68%) were male. All subjects completed the protocol. At baseline, LV masses were 197 ± 76 g and 205 ± 82 g in the placebo and atorvastatin groups, respectively. After 12 months treatment, the LV masses in the placebo and atorvastatin groups were 196 ± 80 versus 206 ± 92 g (P = 0.80), respectively. Echocardiographic indices were not different in the two groups at baseline. After 12 months, diastolic dysfunction as assessed using transmitral flow velocities E/E', A/A', and peak systolic mitral velocity showed no benefit from atorvastatin. Conclusions: In patients with HCM, atorvastatin did not cause LV mass regression or improvements in LV diastolic function.

  20. The Role of Leucine-Rich Repeat Containing Protein 10 (LRRC10) in Dilated Cardiomyopathy

    PubMed Central

    Brody, Matthew J.; Lee, Youngsook

    2016-01-01

    Leucine-rich repeat containing protein 10 (LRRC10) is a cardiomyocyte-specific member of the Leucine-rich repeat containing (LRRC) protein superfamily with critical roles in cardiac function and disease pathogenesis. Recent studies have identified LRRC10 mutations in human idiopathic dilated cardiomyopathy (DCM) and Lrrc10 homozygous knockout mice develop DCM, strongly linking LRRC10 to the molecular etiology of DCM. LRRC10 localizes to the dyad region in cardiomyocytes where it can interact with actin and α-actinin at the Z-disc and associate with T-tubule components. Indeed, this region is becoming increasingly recognized as a signaling center in cardiomyocytes, not only for calcium cycling, excitation-contraction coupling, and calcium-sensitive hypertrophic signaling, but also as a nodal signaling hub where the myocyte can sense and respond to mechanical stress. Disruption of a wide range of critical structural and signaling molecules in cardiomyocytes confers susceptibility to cardiomyopathies in addition to the more classically studied mutations in sarcomeric proteins. However, the molecular mechanisms underlying DCM remain unclear. Here, we review what is known about the cardiomyocyte functions of LRRC10, lessons learned about LRRC10 and DCM from the Lrrc10 knockout mouse model, and discuss ongoing efforts to elucidate molecular mechanisms whereby mutation or absence of LRRC10 mediates cardiac disease. PMID:27536250

  1. The MEF2A gene is excluded as a candidate in 3 families with cardiomyopathies that are not linked to myosin

    SciTech Connect

    Bachinski, L.L.; Abchee, A.; Krahe, R.

    1994-09-01

    Inherited cardiomyopathies, as exemplified by hypertrophic cardiomyopathy (HCM) and idiopathic dilated cardiomyopathy (DCM), are genetically heterogeneous disorders of the myocardium which serve as paradigms for the growth response of the heart to most stimuli. HCM is an autosomal dominant disease shown to be caused by at least 5 different genes, but {beta}-myosin heavy chain (MYH7) is the only one of these genes to be identified to date. No loci have as yet been identified for DCM. MEF2A is one of at least 4 known MEF2 genes which are members of the MADS box family of transcription factors. MEF2A is expressed in cardiac tissue; thus MEF2A is a logical candidate gene for these disorders of the cardiac growth response. We have investigated the possibility of linkage between a trinucleotide repeat polymorphism in the MEF2A gene and these cardiomyopathies is a DCM family and 2 HCM families not linked to MYH7. MEF2A was excluded as a candidate for DCM (LOD of -9.03) and HCM (LODs of-5.43 and -2.44) in these families. No expansion of this trinucleotide repeat was seen in 100 unrelated HCM probands or in the DCM family, which appears to exhibit anticipation.

  2. [Peripartum cardiomyopathy--a case report].

    PubMed

    Banaczek, Zbigniew; Rak, Grzegorz; Gołyska-Rączkiewicz, Danuta

    2015-01-01

    Peripartum cardiomyopathy, a type of dilated cardiomyopathy of unknown origin, occurs in previously healthy women in the final month of pregnancy and up to 5 months after delivery. Although the incidence is low--less than 0.1% of pregnancies--morbidity and mortality rates are high at 5% to 32%. The etiology of left ventricular dysfunction is unknown. Diagnosis of peripartum cardiomyopathy requires heightened awareness among multidisciplinary patient care teams and a high degree of suspicion. Confirmation involves the echocardiography reveals severe left ventricular failure. The outcome of peripartum cardiomyopathy is also highly variable. For some women, the clinical and echocardiographic status improves and sometimes returns to normal, whereas for others, the disease progresses to severe cardiac failure and even sudden cardiac death. Management of peripartum cardiomyopathy should aim first at improving heart-failure symptoms through conventional therapies, and then at administering targeted therapies.The prognosis is best when peripartum cardiomyopathy is diagnosed and treated early. Fortunately, despite a high risk of recurrence in subsequent pregnancies, many patients with peripartum cardiomyopathy recover within 3 to 6 months of disease onset. Future pregnancy is not recommended especially in patients with persistent left ventricular dysfunction because of the risk of dangerous complications.

  3. Childhood Cardiomyopathies: A Study in Tertiary Care Hospital in Upper Egypt

    PubMed Central

    Bakeet, Mohamed Abd Elaal; Mohamed, Montaser Mohamed; Allam, Ahmed Ahmed; Gamal, Rania

    2016-01-01

    Introduction Cardiomyopathy (CMP) is defined by the World Health Organization (WHO) as a disease of the myocardium associated with cardiac dysfunction. An understanding of CMP is very important, as it is a common cause of heart failure in children, and the most common indication for heart transplantation in children older than one year, but data on CMP in Egypt are scarce. The aim of this study was to determine the number, risk factors, clinical presentation, complications and outcome of different types of childhood cardiomyopathies in Sohag University Hospital. Methods This cross-sectional hospital based study enrolled fifty children with Cardiomyopathy in Pediatric Departments, Neonatal Care Units, and Cardiac Outpatient Clinics in Sohag University Hospital from March 01, 2014 to February 28, 2015. Results Cases with Dilated Cardiomyopathy (DCMP) were 38 (76%), and those who had Hypertrophic Cardiomyopathy (HCMP) were 12 (24%). Dyspnea was the most common presenting complaint in 71% of cases. In cases with DCMP, the mean EF was 33.8, and FS was 17.11, while in cases with HCMP, the mean EF was 70.75, FS was 37. Fifty percent of cases were found to have moderate to severe PHT. Serum CK-MB was elevated in 3 (6%) cases, while serum Troponin I was elevated in 2 (4.2%) cases who diagnosed as having myocarditis. Viral myocarditis was the most common identified etiological agent responsible for 14 (37%) cases with DCMP. Conclusions CMP represents a considerable percentage of children with cardiac disorders. DCMP is the most common type, usually presented with congestive heart failure, and the most common cause is myocarditis. L-Carnitine profile was normal in all cases, despite its routine use. Pediatricians need to raise their clinical suspicion to CMPs, as atypical presentations are not uncommon. To do screening for other family members, cardiac enzymes (CK-MB, Troponin I) have to be done in all newly diagnosed CMP cases, along with a revision of the routine

  4. Transformation of myocarditis and inflammatory cardiomyopathy to idiopathic dilated cardiomyopathy: facts and fiction.

    PubMed

    Figulla, Hans R

    2004-05-01

    There is broad evidence that enteroviruses and adenoviruses can induce an acute inflammation of the myocardium without cardiac dysfunction (i.e. myocarditis) or with cardiac dysfunction (i.e. inflammatory cardiomyopathy) that can transform to a virus-negative dilated cardiomyopathy. In the adult patient neither other viruses (parvo-B 19 virus, hepatitis C virus, cytomegalovirus) nor post-infection autoimmunity are likely to induce idiopathic dilated cardiomyopathy.

  5. Takotsubo cardiomyopathy due to iatrogenic methadone withdrawal.

    PubMed

    Saiful, Faisal B; Lafferty, James; Jun, Chin Hee; Teli, Sumaya; Duvvuri, Srinivas; Khattri, Saakshi; Bhat, Tariq

    2011-01-01

    Takotsubo cardiomyopathy is a syndrome characterized by transient apical ballooning or reversible midventricular systolic dysfunction. Most cases occur in postmenopausal women and are typically triggered by an acute medical illness or emotional or physical stress. Its presentation is highly suggestive of myocardial ischemia, but there is little or no evidence of epicardial coronary artery disease. To our knowledge there are only three reported cases in the literature of Takotsubo cardiomyopathy induced by opioid agonist withdrawal in adults; ours is the first reported case of iatrogenic methadone withdrawal leading to Takotsubo cardiomyopathy.

  6. Knock-out of nexilin in mice leads to dilated cardiomyopathy and endomyocardial fibroelastosis.

    PubMed

    Aherrahrou, Zouhair; Schlossarek, Saskia; Stoelting, Stephanie; Klinger, Matthias; Geertz, Birgit; Weinberger, Florian; Kessler, Thorsten; Aherrahrou, Redouane; Moreth, Kristin; Bekeredjian, Raffi; Hrabě de Angelis, Martin; Just, Steffen; Rottbauer, Wolfgang; Eschenhagen, Thomas; Schunkert, Heribert; Carrier, Lucie; Erdmann, Jeanette

    2016-01-01

    Cardiomyopathy is one of the most common causes of chronic heart failure worldwide. Mutations in the gene encoding nexilin (NEXN) occur in patients with both hypertrophic and dilated cardiomyopathy (DCM); however, little is known about the pathophysiological mechanisms and relevance of NEXN to these disorders. Here, we evaluated the functional role of NEXN using a constitutive Nexn knock-out (KO) mouse model. Heterozygous (Het) mice were inter-crossed to produce wild-type (WT), Het, and homozygous KO mice. At birth, 32, 46, and 22 % of the mice were WT, Het, and KO, respectively, which is close to the expected Mendelian ratio. After postnatal day 6, the survival of the Nexn KO mice decreased dramatically and all of the animals died by day 8. Phenotypic characterizations of the WT and KO mice were performed at postnatal days 1, 2, 4, and 6. At birth, the relative heart weights of the WT and KO mice were similar; however, at day 4, the relative heart weight of the KO group was 2.3-fold higher than of the WT group. In addition, the KO mice developed rapidly progressive cardiomyopathy with left ventricular dilation and wall thinning and decreased cardiac function. At day 6, the KO mice developed a fulminant DCM phenotype characterized by dilated ventricular chambers and systolic dysfunction. At this stage, collagen deposits and some elastin deposits were observed within the left ventricle cavity, which resembles the features of endomyocardial fibroelastosis (EFE). Overall, these results further emphasize the role of NEXN in DCM and suggest a novel role in EFE.

  7. Functional Characterization of TNNC1 Rare Variants Identified in Dilated Cardiomyopathy*

    PubMed Central

    Pinto, Jose Renato; Siegfried, Jill D.; Parvatiyar, Michelle S.; Li, Duanxiang; Norton, Nadine; Jones, Michelle A.; Liang, Jingsheng; Potter, James D.; Hershberger, Ray E.

    2011-01-01

    TNNC1, which encodes cardiac troponin C (cTnC), remains elusive as a dilated cardiomyopathy (DCM) gene. Here, we report the clinical, genetic, and functional characterization of four TNNC1 rare variants (Y5H, M103I, D145E, and I148V), all previously reported by us in association with DCM (Hershberger, R. E., Norton, N., Morales, A., Li, D., Siegfried, J. D., and Gonzalez-Quintana, J. (2010) Circ. Cardiovasc. Genet. 3, 155–161); in the previous study, two variants (Y5H and D145E) were identified in subjects who also carried MYH7 and MYBPC3 rare variants, respectively. Functional studies using the recombinant human mutant cTnC proteins reconstituted into porcine papillary skinned fibers showed decreased Ca2+ sensitivity of force development (Y5H and M103I). Furthermore, the cTnC mutants diminished (Y5H and I148V) or abolished (M103I) the effects of PKA phosphorylation on Ca2+ sensitivity. Only M103I decreased the troponin activation properties of the actomyosin ATPase when Ca2+ was present. CD spectroscopic studies of apo (absence of divalent cations)-, Mg2+-, and Ca2+/Mg2+-bound states indicated that all of the cTnC mutants (except I148V in the Ca2+/Mg2+ condition) decreased the α-helical content. These results suggest that each mutation alters the function/ability of the myofilament to bind Ca2+ as a result of modifications in cTnC structure. One variant (D145E) that was previously reported in association with hypertrophic cardiomyopathy and that produced results in vivo in this study consistent with prior hypertrophic cardiomyopathy functional studies was found associated with the MYBPC3 P910T rare variant, likely contributing to the observed DCM phenotype. We conclude that these rare variants alter the regulation of contraction in some way, and the combined clinical, molecular, genetic, and functional data reinforce the importance of TNNC1 rare variants in the pathogenesis of DCM. PMID:21832052

  8. Hypertrophic pyloric stenosis in the third world.

    PubMed

    Saula, P W; Hadley, G P

    2011-10-01

    The relative rarity of hypertrophic pyloric stenosis (HPS) in the developing world makes its diagnosis a challenge to many physicians. This study audits the management of HPS at a tertiary hospital in South Africa, with a view to defining its regional pattern. This is a retrospective review of records of all patients (n = 63) managed for HPS over an eight-year period (2002-2010). The mean age at presentation was 6.2 weeks and the male/female ratio was 6:1. The majority of patients presented with non-bilious vomiting. Abdominal ultrasound had a sensitivity of 65% and 81.3% when the criteria of pyloric muscle thickness >4 mm and pyloric channel length >16 mm were used, respectively. The overall complication rate was 14.3% and the mortality rate was 0%. Despite the rarity of HPS in the Third World, the outcome of its management is favourable. However, the sensitivity of abdominal ultrasound for diagnosing HPS is low.

  9. Paraneoplastic hypertrophic osteopathy in 30 dogs

    PubMed Central

    Withers, S. S.; Johnson, E. G.; Culp, W. T. N.; Rodriguez, C. O.; Skorupski, K. A.; Rebhun, R. B.

    2016-01-01

    Paraneoplastic hypertrophic osteopathy (pHO) is known to occur in both canine and human cancer patients. While the pathology of pHO is well-described in the dog, very little information exists regarding the true clinical presentation of dogs affected with pHO. The primary objective of this study was to provide a more comprehensive clinical picture of pHO. To this end, we retrospectively identified 30 dogs and recorded data regarding presenting complaints and physical examination (PE) findings on the date of pHO diagnosis. As a secondary objective, any blood test results were also collected from the computerized records. The most common clinical signs included leg swelling, ocular discharge and/or episcleral injection, lameness, and lethargy. The most common haematological and serum biochemical abnormalities included anaemia, neutrophilia and elevated alkaline phosphatase. In addition to presenting a more detailed clinical description of pHO in the dog, these data support the previously described haematological, serum biochemical and PE abnormalities published in individual case reports. PMID:23489591

  10. Hypertrophic olivary degeneration secondary to pontine haemorrhage.

    PubMed

    Wein, Sara; Yan, Bernard; Gaillard, Frank

    2015-07-01

    We report a 58-year-old man who developed hyptertrophic olivary degeneration (HOD) after haemorrhage of a cavernous malformation in the pons. Lesions of the triangle of Guillain and Mollaret (the dentatorubro-olivary pathway) may lead to HOD, a secondary transsynaptic degeneration of the inferior olivary nucleus. HOD is considered unique because the degenerating olive initially becomes hypertrophic rather than atrophic. The primary lesion causing pathway interruption is often haemorrhage, either due to hypertension, trauma, surgery or, as in our patient, a vascular malformation such as a cavernoma. Ischaemia and demyelination can also occasionally be the inciting events. The classic clinical presentation of HOD is palatal myoclonus, although not all patients with HOD develop this symptom. The imaging features of HOD evolve through characteristic phases. The clue to the diagnosis of HOD is recognition of the distinct imaging stages and identification of a remote primary lesion in the triangle of Guillain and Mollaret. Familiarity with the classic imaging findings of this rare phenomenon is necessary in order to avoid misdiagnosis and prevent unnecessary intervention.

  11. Paraneoplastic hypertrophic osteopathy in 30 dogs.

    PubMed

    Withers, S S; Johnson, E G; Culp, W T N; Rodriguez, C O; Skorupski, K A; Rebhun, R B

    2015-09-01

    Paraneoplastic hypertrophic osteopathy (pHO) is known to occur in both canine and human cancer patients. While the pathology of pHO is well-described in the dog, very little information exists regarding the true clinical presentation of dogs affected with pHO. The primary objective of this study was to provide a more comprehensive clinical picture of pHO. To this end, we retrospectively identified 30 dogs and recorded data regarding presenting complaints and physical examination (PE) findings on the date of pHO diagnosis. As a secondary objective, any blood test results were also collected from the computerized records. The most common clinical signs included leg swelling, ocular discharge and/or episcleral injection, lameness, and lethargy. The most common haematological and serum biochemical abnormalities included anaemia, neutrophilia and elevated alkaline phosphatase. In addition to presenting a more detailed clinical description of pHO in the dog, these data support the previously described haematological, serum biochemical and PE abnormalities published in individual case reports.

  12. Interplay between the E2F pathway and β-adrenergic signaling in the pathological hypertrophic response of myocardium.

    PubMed

    Major, Jennifer L; Salih, Maysoon; Tuana, Balwant S

    2015-07-01

    The E2F/Pocket protein (Rb) pathway regulates cell growth, differentiation, and death by modulating gene expression. We previously examined this pathway in the myocardium via manipulation of the unique E2F repressor, E2F6, which is believed to repress gene activity independently of Rb. Mice with targeted expression of E2F6 in postnatal myocardium developed dilated cardiomyopathy (DCM) without hypertrophic growth. We assessed the mechanisms of the apparent failure of compensatory hypertrophic growth as well as their response to the β-adrenergic agonist isoproterenol. As early as 2 weeks, E2F6 transgenic (Tg) mice present with dilated thinner left ventricles and significantly reduced ejection fraction and fractional shortening which persists at 6 weeks of age, but with no apparent increase in left ventricle weight: body weight (LVW:BW). E2F6-Tg mice treated with isoproterenol (6.1 mg/kg/day) show double the increase in LVW:BW than their Wt counterparts (32% vs 16%, p-value: 0.007). Western blot analysis revealed the activation of the adrenergic pathway in Tg heart tissue under basal conditions with ~2-fold increase in the level of β2-adrenergic receptors (p-value: 8.9E-05), protein kinase A catalytic subunit (PKA-C) (p-value: 0.0176), activated c-Src tyrosine-protein kinase (p-value: 0.0002), extracellular receptor kinase 2 (ERK2) (p-value: 0.0005), and induction of the anti-apoptotic protein Bcl2 (p-value 0. 0.00001). In contrast, a ~60% decrease in the cardiac growth regulator: AKT1 (p-value 0.0001) and a ~four fold increase in cyclic AMP dependent phosphodiesterase 4D (PDE4D), the negative regulator of PKA activity, were evident in the myocardium of E2F6-Tg mice. The expression of E2F3 was down-regulated by E2F6, but was restored by isoproterenol. Further, Rb expression was down-regulated in Tg mice in response to isoproterenol implying a net activation of the E2F pathway. Thus the unique regulation of E2F activity by E2F6 renders the myocardium hypersensitive

  13. Penile agenesis and congenital hypertrophic pyloric stenosis: an association or a random coexistence?

    PubMed

    Yagmurlu, Aydin; Vargun, Rahsan; Gollu, Gulnur; Gokcora, I Haluk

    2004-01-01

    A neonate with penile agenesis and congenital hypertrophic pyloric stenosis is presented. The patterns of associated anomalies with penile agenesis, and those of congenital hypertrophic pyloric stenosis are discussed.

  14. Echocardiographic differences between preeclampsia and peripartum cardiomyopathy.

    PubMed

    Dennis, A T; Castro, J M

    2014-08-01

    Peripartum heart failure due to preeclampsia or peripartum cardiomyopathy represents a significant global health issue. Transthoracic echocardiography enables differentiation of heart failure with preserved ejection fraction, commonly observed in women with preeclampsia, from that with peripartum cardiomyopathy in which a reduced ejection fraction is more common. An understanding of the different definitions and diagnostic features of these two diseases, as well as accurate characterisation of the haemodynamics in preeclampsia and peripartum cardiomyopathy, allows clinicians to manage these conditions appropriately. This article outlines the echocardiographic differences between preeclampsia and peripartum cardiomyopathy, the likely mechanisms for heart failure in preeclampsia and the relevance of these differences to clinicians in relation to prevention and treatment. It also emphasises the importance of disease definitions as a key framework for the more consistent classification of the two diseases.

  15. [Takotsubo cardiomyopathy in a cardiology department].

    PubMed

    Cesário, Vera; Loureiro, Maria José; Pereira, Hélder

    2012-09-01

    Takotsubo cardiomyopathy, also known as transient left ventricular apical ballooning syndrome, stress-induced cardiomyopathy and broken heart syndrome, is characterized by transient left ventricular dysfunction in the absence of obstructive coronary artery disease. It was first described in 1990 in Japan, and gained worldwide recognition following the publication of several series of case reports. Its prevalence is estimated to be 1.7-2.2% of suspected acute coronary syndromes. Although takotsubo cardiomyopathy has been progressively better characterized, certain aspects remain to be clarified, and it is still under study. In this article, we report a series of ten cases of takotsubo cardiomyopathy admitted to a cardiology department, and compare the clinical, laboratory, electrocardiographic and imaging characteristics, therapeutic regimens and follow-up of these patients with those described in the latest scientific reviews.

  16. [Echocardiography methods in the diagnosis of cardiomyopathies in children].

    PubMed

    First, T; Skovránek, J

    1988-12-16

    We investigated 59 children with cardiomyopathy (CMP) by echocardiographic methods (ECHO). 29 children with dilated CMP showed typical enlargement of the left ventricle 159 +/- 31%, xxx; (% of normal value +/- SD) and of the left atrium (143 +/- 27%, xxx). Systolic and diastolic function of the left ventricle were decreased, systolic change in size of the left ventricle % delta D = 16 +/- 7%; xxx; systolic change in area of the left ventricle % delta A = 20 +/- 8%; xxx; maximum filling rate of the left ventricle in the phase of quick filling E max = 0.37 +/- 0.09 m. sec-1, xxx; the percentage of filling in the first third of diastole 0.33 DA = 37 +/- 9%, xx. Mitral insufficiency was found by us in 81% of children. In 25 children with hypertrophic CMP the size of left ventricle was decreased (81 +/- 13%, xxx). Asymmetric septal hypertrophy was found by us in 69% of children, symmetric hypertrophy in 27%, local hypertrophy of the apex in 4%. Systolic function of the left ventricle was increased (% delta D = 47 +/- 10%, xxx; % delta A = 70 +/- 10%, xxx). Diastolic dysfunction manifested itself by reduced E max (0.71 +/- 0.19 m.sec-1, xx) and 0.33 DA (45 +/- 12%, x). Mitral insufficiency was found in 54% of the children. In the case of the 5 children with restrictive CMP an extreme enlargement of left atrium (195 +/- 41%, xxx) was typical, as well as diastolic dysfunction of the left ventricle (0.33 DA = 67 +/- 6%, x).(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Medicinal Plants for the Treatment of Hypertrophic Scars

    PubMed Central

    Ye, Qi; Wang, Su-Juan; Chen, Jian-Yu; Xin, Hai-Liang; Zhang, Hong

    2015-01-01

    Hypertrophic scar is a complication of wound healing and has a high recurrence rate which can lead to significant abnormity in aesthetics and functions. To date, no ideal treatment method has been established. Meanwhile, the underlying mechanism of hypertrophic scarring has not been clearly defined. Although a large amount of scientific research has been reported on the use of medicinal plants as a natural source of treatment for hypertrophic scarring, it is currently scattered across a wide range of publications. Therefore, a systematic summary and knowledge for future prospects are necessary to facilitate further medicinal plant research for their potential use as antihypertrophic scar agents. A bibliographic investigation was accomplished by focusing on medicinal plants which have been scientifically tested in vitro and/or in vivo and proved as potential agents for the treatment of hypertrophic scars. Although the chemical components and mechanisms of action of medicinal plants with antihypertrophic scarring potential have been investigated, many others remain unknown. More investigations and clinical trials are necessary to make use of these medical plants reasonably and phytotherapy is a promising therapeutic approach against hypertrophic scars. PMID:25861351

  18. Takotsubo Cardiomyopathy: A New Perspective in Asthma

    PubMed Central

    Marmoush, Fady Y.; Barbour, Mohamad F.; Noonan, Thomas E.; Al-Qadi, Mazen O.

    2015-01-01

    Takotsubo cardiomyopathy (TCM) is an entity of reversible cardiomyopathy known for its association with physical or emotional stress and may mimic myocardial infarction. We report an exceedingly rare case of albuterol-induced TCM with moderate asthma exacerbation. An interesting association that may help in understanding the etiology of TCM in the asthmatic population. Although the prognosis of TCM is excellent, it is crucial to recognize beta agonists as a potential stressor. PMID:26246918

  19. Takotsubo Cardiomyopathy Occurring in the Postoperative Period.

    PubMed

    Deniz, Süleyman; Bakal, Ömer; İnangil, Gökhan; Şen, Hüseyin; Özkan, Sezai

    2015-02-01

    Takotsubo cardiomyopathy simulates acute myocardial infarction, and it is characterised by reversible left ventricular failure. A case of Takotsubo cardiomyopathy diagnosed after emergency angiography performed in a patient with evidence of acute myocardial infarction in the postoperative period will be described in this report. Transurethral resection of a bladder tumour (TUR-BT) was performed in a 92-year-old male patient by the urology clinic. The patient was transferred to the post-anaesthesia care unit after the operation. An echocardiography was performed because of the sudden onset of dyspnoea, tachycardia (140-150 beats per minute, rhythm-atrial fibrillation) and ST-segment elevation on electrocardiography (ECG) at the first postoperative hour, and midapical dyskinesia was detected at the patient. An immediate angiography was performed due to suspicion of acute coronary syndrome. Patent coronary arteries and temporary aneurysmatic dilatation of the apex of the heart were revealed by angiography. As a result of these findings, the patient was diagnosed with Takotsubo cardiomyopathy by the cardiology service. The patient was discharged uneventfully following 10 days in the intensive care unit. Aneurysm of the apex of the left ventricle and normal anatomy of the coronary arteries in the angiography have diagnostic value for Takotsubo cardiomyopathy. Diuretics (furosemide) and beta-blockers (metoprolol) are commonly used for the treatment of Takotsubo cardiomyopathy. Even though Takotsubo cardiomyopathy is a rare and benign disease, it should be kept in mind in patients suspected for acute myocardial infarction in the postoperative period.

  20. [Peripartum cardiomyopathy: A multiple entity].

    PubMed

    Vanzetto, Gérald; Martin, Alix; Bouvaist, Hélène; Marlière, Stéphanie; Durand, Michel; Chavanon, Olivier

    2012-06-01

    Peripartum cardiomyopathy (PPCMP) is a dilated and hypokinetic cardiomyopathy occurring during pregnancy or after delivery, with an estimated incidence between 1/1000 and 1/4000 births. It has been defined as a new onset of heart failure in the month preceding or following delivery, without demonstrated aetiology nor previously known heart disease, and with echocardiographic evidences of left ventricular (LV) dysfunction (LV ejection fraction<0.45). It's a multifactorial disease, immunologic, hormonal, and possibly viral mechanisms playing a determinant pathophysiological role. The classical clinical presentation is a rapid and unexpected onset of heart failure in a previously healthy woman, echocardiography being the key examination for positive and differential diagnosis, prognostication, therapeutic decision-making, and follow-up. The potential severity of PPCMP, and its unpredictable evolution in the first days following diagnosis, require that patients be referred to a tertiary care centre with a high skill in intensive cardiology care. Therapeutic management of PPCMP does not offer any specificity when compared to other causes of acute or chronic heart failure (from diuretics to extracorporeal life support), except for ACE-inhibitors, that are contraindicated before delivery. The high incidence of thrombo-embolic complications observed in the disease requires however rapid and curative anticoagulation, and immuno-suppressive treatment has been proposed in fulminant and highly inflammatory presentation, but its efficacy remains controversial. Very recently, promising results have been reported with bromocriptin-a prolactin secretion inhibitor-for reducing 6-month morbidity and mortality, but these findings have to be confirmed in larger scale randomised trials. As for the long-term evolution, approximately half of the patients will heal, while half of the women will keep some degree of LV dysfunction, 25% of them developing moderate to severe chronic heart

  1. Cardiomyopathy

    MedlinePlus

    ... the myocardium and endocardium. In Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 25th ed. Philadelphia, PA: ... failure: management and diagnosis. In Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 25th ed. Philadelphia, PA: ...

  2. Cardiomyopathy

    MedlinePlus

    ... to grow in the heart and other organs (sarcoidosis) A disorder that causes the buildup of abnormal ... to grow in the heart and other organs (sarcoidosis), connective tissue disorders, or a disorder that causes ...

  3. Familial idiopathic hypertrophic osteoarthropathy and cranial suture defects in children

    SciTech Connect

    Reginato, A.J.; Schiapachasse, V.; Guerrero, R.

    1982-05-01

    Three children with idiopathic hypertrophic osteoarthropathy and cranial suture defects are reported. The syndrome was recognized after birth and in the two oldest siblings, the cranial defects and subperiosteal bone formation resolved almost completely by age 4 and 6 years. The joint swelling and clubbing persisted and mild bone reabsorption of the distal phalanges became apparent at an older age. Two siblings and both parents had normal bone X-rays and no clubbing. This study confirms the association of cranial sutural defects and familial idopathic hypertrophic osteoarthropathy.

  4. Identification of novel mutations including a double mutation in patients with inherited cardiomyopathy by a targeted sequencing approach using the Ion Torrent PGM system

    PubMed Central

    ZHAO, YUE; CAO, HONG; SONG, YINDI; FENG, YUE; DING, XIAOXUE; PANG, MINGJIE; ZHANG, YUNMEI; ZHANG, HONG; DING, JIAHUAN; XIA, XUESHAN

    2016-01-01

    Inherited cardiomyopathy is the major cause of sudden cardiac death (SCD) and heart failure (HF). The disease is associated with extensive genetic heterogeneity; pathogenic mutations in cardiac sarcomere protein genes, cytoskeletal protein genes and nuclear envelope protein genes have been linked to its etiology. Early diagnosis is conducive to clinical monitoring and allows for presymptomatic interventions as needed. In the present study, the entire coding sequences and flanking regions of 12 major disease (cardiomyopathy)-related genes [namely myosin, heavy chain 7, cardiac muscle, β (MYH7); myosin binding protein C, cardiac (MYBPC3); lamin A/C (LMNA); troponin I type 3 (cardiac) (TNNI3); troponin T type 2 (cardiac) (TNNT2); actin, α, cardiac muscle 1 (ACTC1); tropomyosin 1 (α) (TPM1); sodium channel, voltage gated, type V alpha subunit (SCN5A); myosin, light chain 2, regulatory, cardiac, slow (MYL2); myosin, heavy chain 6, cardiac muscle, α (MYH6); myosin, light chain 3, alkali, ventricular, skeletal, slow (MYL3); and protein kinase, AMP-activated, gamma 2 non-catalytic subunit (PRKAG2)] in 8 patients with dilated cardiomyopathy (DCM) and in 8 patients with hypertrophic cardiomyopathy (HCM) were amplified and then sequenced using the Ion Torrent Personal Genome Machine (PGM) system. As a result, a novel heterozygous mutation (MYH7, p.Asn885Thr) and a variant of uncertain significance (TNNT2, p.Arg296His) were identified in 2 patients with HCM. These 2 missense mutations, which were absent in the samples obtained from the 200 healthy control subjects, altered the amino acid that was evolutionarily conserved among a number of vertebrate species; this illustrates that these 2 non-synonymous mutations play a role in the pathogenesis of HCM. Moreover, a double heterozygous mutation (PRKAG2, p.Gly100Ser plus MYH7, p.Arg719Trp) was identified in a patient with severe familial HCM, for the first time to the best of our knowledge. This patient provided us with more

  5. Molecular-genetic characterization and rescue of a TSFM mutation causing childhood-onset ataxia and nonobstructive cardiomyopathy.

    PubMed

    Emperador, Sonia; Bayona-Bafaluy, M Pilar; Fernández-Marmiesse, Ana; Pineda, Mercedes; Felgueroso, Blanca; López-Gallardo, Ester; Artuch, Rafael; Roca, Iria; Ruiz-Pesini, Eduardo; Couce, María Luz; Montoya, Julio

    2016-01-01

    Oxidative phosphorylation dysfunction has been found in many different disorders. This biochemical pathway depends on mitochondrial protein synthesis. Thus, mutations in components of the mitochondrial translation system can be responsible for some of these pathologies. We identified a new homozygous missense mutation in the mitochondrial translation elongation factor Ts gene in a patient suffering from slowly progressive childhood ataxia and hypertrophic cardiomyopathy. Using cell, biochemical and molecular-genetic protocols, we confirm it as the etiologic factor of this phenotype. Moreover, as an important functional confirmation, we rescued the normal molecular phenotype by expression of the wild-type TSFM cDNA in patient's fibroblasts. Different TSFM mutations can produce the same or very different clinical phenotypes, going from abortions to moderately severe presentations. On the other hand, the same TSFM mutation can also produce same or different phenotypes within the same range of presentations, therefore suggesting the involvement of unknown factors.

  6. Arterial microembolisation: an unusual presentation of dilated cardiomyopathy.

    PubMed Central

    Gillespie, R L; Mullen, G M; Costanzo-Nordin, M R

    1990-01-01

    Systemic embolisation is common in patients with dilated cardiomyopathy. Microembolisation as a presenting sign of dilated cardiomyopathy, however, has not been reported before. A 37 year old woman in whom dilated cardiomyopathy presented as arterial microembolisation to the toes is described. Images PMID:2310647

  7. High Frequency QRS ECG Accurately Detects Cardiomyopathy

    NASA Technical Reports Server (NTRS)

    Schlegel, Todd T.; Arenare, Brian; Poulin, Gregory; Moser, Daniel R.; Delgado, Reynolds

    2005-01-01

    High frequency (HF, 150-250 Hz) analysis over the entire QRS interval of the ECG is more sensitive than conventional ECG for detecting myocardial ischemia. However, the accuracy of HF QRS ECG for detecting cardiomyopathy is unknown. We obtained simultaneous resting conventional and HF QRS 12-lead ECGs in 66 patients with cardiomyopathy (EF = 23.2 plus or minus 6.l%, mean plus or minus SD) and in 66 age- and gender-matched healthy controls using PC-based ECG software recently developed at NASA. The single most accurate ECG parameter for detecting cardiomyopathy was an HF QRS morphological score that takes into consideration the total number and severity of reduced amplitude zones (RAZs) present plus the clustering of RAZs together in contiguous leads. This RAZ score had an area under the receiver operator curve (ROC) of 0.91, and was 88% sensitive, 82% specific and 85% accurate for identifying cardiomyopathy at optimum score cut-off of 140 points. Although conventional ECG parameters such as the QRS and QTc intervals were also significantly longer in patients than controls (P less than 0.001, BBBs excluded), these conventional parameters were less accurate (area under the ROC = 0.77 and 0.77, respectively) than HF QRS morphological parameters for identifying underlying cardiomyopathy. The total amplitude of the HF QRS complexes, as measured by summed root mean square voltages (RMSVs), also differed between patients and controls (33.8 plus or minus 11.5 vs. 41.5 plus or minus 13.6 mV, respectively, P less than 0.003), but this parameter was even less accurate in distinguishing the two groups (area under ROC = 0.67) than the HF QRS morphologic and conventional ECG parameters. Diagnostic accuracy was optimal (86%) when the RAZ score from the HF QRS ECG and the QTc interval from the conventional ECG were used simultaneously with cut-offs of greater than or equal to 40 points and greater than or equal to 445 ms, respectively. In conclusion 12-lead HF QRS ECG employing

  8. Insulin resistance and hyperinsulinaemia in diabetic cardiomyopathy

    PubMed Central

    Jia, Guanghong; DeMarco, Vincent G.; Sowers, James R.

    2016-01-01

    Insulin resistance, type 2 diabetes mellitus and associated hyperinsulinaemia can promote the development of a specific form of cardiomyopathy that is independent of coronary artery disease and hypertension. Termed diabetic cardiomyopathy, this form of cardiomyopathy is a major cause of morbidity and mortality in developed nations, and the prevalence of this condition is rising in parallel with increases in the incidence of obesity and type 2 diabetes mellitus. Of note, female patients seem to be particularly susceptible to the development of this complication of metabolic disease. The diabetic cardiomyopathy observed in insulin-resistant or hyperinsulinaemic states is characterized by impaired myocardial insulin signalling, mitochondrial dysfunction, endoplasmic reticulum stress, impaired calcium homeostasis, abnormal coronary microcirculation, activation of the sympathetic nervous system, activation of the renin–angiotensin–aldosterone system and maladaptive immune responses. These pathophysiological changes result in oxidative stress, fibrosis, hypertrophy, cardiac diastolic dysfunction and eventually systolic heart failure. This Review highlights a surge in diabetic cardiomyopathy research, summarizes current understanding of the molecular mechanisms underpinning this condition and explores potential preventive and therapeutic strategies. PMID:26678809

  9. Cardiomyopathy in captive African hedgehogs (Atelerix albiventris).

    PubMed

    Raymond, J T; Garner, M M

    2000-09-01

    From 1994 to 1999, 16 captive African hedgehogs (Atelerix albiventris), from among 42 necropsy cases, were diagnosed with cardiomyopathy. The incidence of cardiomyopathy in this study population was 38%. Fourteen of 16 hedgehogs with cardiomyopathy were males and all hedgehogs were adult (>1 year old). Nine hedgehogs exhibited 1 or more of the following clinical signs before death: heart murmur, lethargy, icterus, moist rales, anorexia, dyspnea, dehydration, and weight loss. The remaining 7 hedgehogs died without premonitory clinical signs. Gross findings were cardiomegaly (6 cases), hepatomegaly (5 cases), pulmonary edema (5 cases), pulmonary congestion (4 cases), hydrothorax (3 cases), pulmonary infarct (1 case), renal infarcts (1 case), ascites (1 case), and 5 cases showed no changes. Histologic lesions were found mainly within the left ventricular myocardium and consisted primarily of myodegeneration, myonecrosis, atrophy, hypertrophy, and disarray of myofibers. All hedgehogs with cardiomyopathy had myocardial fibrosis, myocardial edema, or both. Other common histopathologic findings were acute and chronic passive congestion of the lungs, acute passive congestion of the liver, renal tubular necrosis, vascular thrombosis, splenic extramedullary hematopoiesis, and hepatic lipidosis. This is the first report of cardiomyopathy in African hedgehogs.

  10. Adult hypertrophic pyloric stenosis — a description in 1834?

    PubMed Central

    Stout, G.

    1983-01-01

    John Peacock MD was in practice in Darlington when he published his Practical Hints on the Treatment of Several Diseases in 1834. It is suggested that his cases described therein of `scirrhous pylorus' are adult hypertrophic pyloric stenosis. If authenticated, his work would predate the earliest description of this condition by the French pathologist, Professor Jean Cruveilhier in 1835. PMID:6350566

  11. A case of hypertrophic osteoarthropathy in a Belgian blue cow

    PubMed Central

    Guyot, Hugues; Sandersen, Charlotte; Rollin, Frédéric

    2011-01-01

    A 12-year-old cow was presented with chronic respiratory disease and lameness. Chronic pleuritis, pneumonia, and bronchial carcinoma were found as well as periosteal proliferation on limb bones. Ancillary tests and necropsy confirmed a combined pathology of pulmonary inflammation and neoplasm, and hypertrophic pulmonary osteopathy. PMID:22654134

  12. Electrocardiographic predictors of peripartum cardiomyopathy

    PubMed Central

    Karaye, Kamilu M; Karaye, Kamilu M; Lindmark, Krister; Henein, Michael Y; Lindmark, Krister; Henein, Michael Y

    2016-01-01

    Summary Objective To identify potential electrocardiographic predictors of peripartum cardiomyopathy (PPCM). Methods: This was a case–control study carried out in three hospitals in Kano, Nigeria. Logistic regression models and a risk score were developed to determine electrocardiographic predictors of PPCM. Results: A total of 54 PPCM and 77 controls were consecutively recruited after satisfying the inclusion criteria. After controlling for confounding variables, a rise in heart rate of one beat/minute increased the risk of PPCM by 6.4% (p = 0.001), while the presence of ST–T-wave changes increased the odds of PPCM 12.06-fold (p < 0.001). In the patients, QRS duration modestly correlated (r = 0.4; p < 0.003) with left ventricular dimensions and end-systolic volume index, and was responsible for 19.9% of the variability of the latter (R2 = 0.199; p = 0.003). A risk score of ≥ 2, developed by scoring 1 for each of the three ECG disturbances (tachycardia, ST–T-wave abnormalities and QRS duration), had a sensitivity of 85.2%, specificity of 64.9%, negative predictive value of 86.2% and area under the curve of 83.8% (p < 0.0001) for potentially predicting PPCM. Conclusion In postpartum women, using the risk score could help to streamline the diagnosis of PPCM with significant accuracy, prior to confirmatory investigations PMID:27213852

  13. Dilated Cardiomyopathy Revealing Cushing Disease

    PubMed Central

    Marchand, Lucien; Segrestin, Bérénice; Lapoirie, Marion; Favrel, Véronique; Dementhon, Julie; Jouanneau, Emmanuel; Raverot, Gérald

    2015-01-01

    Abstract Cardiovascular impairments are frequent in Cushing's syndrome and the hypercortisolism can result in cardiac structural and functional changes that lead in rare cases to dilated cardiomyopathy (DCM). Such cardiac impairment may be reversible in response to a eucortisolaemic state. A 43-year-old man with a medical past of hypertension and history of smoking presented to the emergency department with global heart failure. Coronary angiography showed a significant stenosis of a marginal branch and cardiac MRI revealed a nonischemic DCM. The left ventricular ejection fraction (LVEF) was estimated as 28% to 30%. Clinicobiological features and pituitary imaging pointed toward Cushing's disease and administration of adrenolytic drugs (metyrapone and ketoconazole) was initiated. Despite the normalization of cortisol which had been achieved 2 months later, the patient presented an acute heart failure. A massive mitral regurgitation secondary to posterior papillary muscle rupture was diagnosed as a complication of the occlusion of the marginal branch. After 6 months of optimal pharmacological treatment for systolic heart failure, as well as treatment with inhibitors of steroidogenesis, there was no improvement of LVEF. The percutaneous mitral valve was therefore repaired and a defibrillator implanted. The severity of heart failure contraindicated pituitary surgery and the patient was instead treated by stereotaxic radiotherapy. This is the first case reporting a Cushing's syndrome DCM without improvement of LVEF despite normalization of serum cortisol levels. PMID:26579807

  14. Cardiac MRI in restrictive cardiomyopathy.

    PubMed

    Gupta, A; Singh Gulati, G; Seth, S; Sharma, S

    2012-02-01

    Restrictive cardiomyopathy (RCM) is a specific group of heart muscle disorders characterized by inadequate ventricular relaxation during diastole. This leads to diastolic dysfunction with relative preservation of systolic function. Although short axis systolic function is usually preserved in RCM, the long axis systolic function may be severely impaired. Confirmation of diagnosis and information regarding aetiology, extent of myocardial damage, and response to treatment requires imaging. Importantly, differentiation from constrictive pericarditis (CCP) is needed, as only the latter is managed surgically. Echocardiography is the initial cardiac imaging technique but cannot reliably suggest a tissue diagnosis; although recent advances, especially tissue Doppler imaging and spectral tracking, have improved its ability to differentiate RCM from CCP. Cardiac catheterization is the reference standard, but is invasive, two-dimensional, and does not aid myocardial characterization. Cardiac magnetic resonance (CMR) is a versatile technique providing anatomical, morphological and functional information. In recent years, it has been shown to provide important information regarding disease mechanisms, and also been found useful to guide treatment, assess its outcome and predict patient prognosis. This review describes the CMR features of RCM, appearances in various diseases, its overall role in patient management, and how it compares with other imaging techniques.

  15. Mitochondrial Dynamics in Diabetic Cardiomyopathy

    PubMed Central

    Galloway, Chad A.

    2015-01-01

    Abstract Significance: Cardiac function is energetically demanding, reliant on efficient well-coupled mitochondria to generate adenosine triphosphate and fulfill the cardiac demand. Predictably then, mitochondrial dysfunction is associated with cardiac pathologies, often related to metabolic disease, most commonly diabetes. Diabetic cardiomyopathy (DCM), characterized by decreased left ventricular function, arises independently of coronary artery disease and atherosclerosis. Dysregulation of Ca2+ handling, metabolic changes, and oxidative stress are observed in DCM, abnormalities reflected in alterations in mitochondrial energetics. Cardiac tissue from DCM patients also presents with altered mitochondrial morphology, suggesting a possible role of mitochondrial dynamics in its pathological progression. Recent Advances: Abnormal mitochondrial morphology is associated with pathologies across diverse tissues, suggesting that this highly regulated process is essential for proper cell maintenance and physiological homeostasis. Highly structured cardiac myofibers were hypothesized to limit alterations in mitochondrial morphology; however, recent work has identified morphological changes in cardiac tissue, specifically in DCM. Critical Issues: Mitochondrial dysfunction has been reported independently from observations of altered mitochondrial morphology in DCM. The temporal relationship and causative nature between functional and morphological changes of mitochondria in the establishment/progression of DCM is unclear. Future Directions: Altered mitochondrial energetics and morphology are not only causal for but also consequential to reactive oxygen species production, hence exacerbating oxidative damage through reciprocal amplification, which is integral to the progression of DCM. Therefore, targeting mitochondria for DCM will require better mechanistic characterization of morphological distortion and bioenergetic dysfunction. Antioxid. Redox Signal. 22, 1545–1562. PMID

  16. Cardiomyocyte Hypertrophy in Arrhythmogenic Cardiomyopathy.

    PubMed

    Gerçek, Mustafa; Gerçek, Muhammed; Kant, Sebastian; Simsekyilmaz, Sakine; Kassner, Astrid; Milting, Hendrik; Liehn, Elisa A; Leube, Rudolf E; Krusche, Claudia A

    2017-04-01

    Arrhythmogenic cardiomyopathy (AC) is a hereditary disease leading to sudden cardiac death or heart failure. AC pathology is characterized by cardiomyocyte loss and replacement fibrosis. Our goal was to determine whether cardiomyocytes respond to AC progression by pathological hypertrophy. To this end, we examined tissue samples from AC patients with end-stage heart failure and tissue samples that were collected at different disease stages from desmoglein 2-mutant mice, a well characterized AC model. We find that cardiomyocyte diameters are significantly increased in right ventricles of AC patients. Increased mRNA expression of the cardiac stress marker natriuretic peptide B is also observed in the right ventricle of AC patients. Elevated myosin heavy chain 7 mRNA expression is detected in left ventricles. In desmoglein 2-mutant mice, cardiomyocyte diameters are normal during the concealed disease phase but increase significantly after acute disease onset on cardiomyocyte death and fibrotic myocardial remodeling. Hypertrophy progresses further during the chronic disease stage. In parallel, mRNA expression of myosin heavy chain 7 and natriuretic peptide B is up-regulated in both ventricles with right ventricular preference. Calcineurin/nuclear factor of activated T cells (Nfat) signaling, which is linked to pathological hypertrophy, is observed during AC progression, as evidenced by Nfatc2 and Nfatc3 mRNA in cardiomyocytes and increased mRNA of the Nfat target regulator of calcineurin 1. Taken together, we demonstrate that pathological hypertrophy occurs in AC and is secondary to cardiomyocyte loss and cardiac remodeling.

  17. Exercise Prescription for the Athlete with Cardiomyopathy.

    PubMed

    Saberi, Sara; Day, Sharlene M

    2016-11-01

    Inherited cardiomyopathies have highly variable expression in terms of symptoms, functional limitations, and disease severity. Associated risk of sudden cardiac death is also variable. International guidelines currently recommend restriction of all athletes with cardiomyopathy from participation in competitive sports. While the guidelines are necessarily conservative because predictive risk factors for exercise-triggered SCD have not been clearly identified, the risk is clearly not uniform across all athletes and all sports. The advent of implantable cardioverter defibrillators, automated external defibrillators, and successful implementation of emergency action plans may safely mitigate risk of sudden cardiac death during physical activity. An individualized approach to risk stratification of athletes that recognizes patient autonomy may allow many individuals with cardiomyopathies to safely train and compete.

  18. Role of Cardiac MR Imaging in Cardiomyopathies.

    PubMed

    Kramer, Christopher M

    2015-06-01

    Cardiac MR imaging has made major inroads in the new millennium in the diagnosis and assessment of prognosis for patients with cardiomyopathies. Imaging of left and right ventricular structure and function and tissue characterization with late gadolinium enhancement (LGE) as well as T1 and T2 mapping enable accurate diagnosis of the underlying etiology. In the setting of coronary artery disease, either transmurality of LGE or contractile reserve in response to dobutamine can assess the likelihood of recovery of function after revascularization. The presence of scar reduces the likelihood of a response to medical therapy and to cardiac resynchronization therapy in heart failure. The presence and extent of LGE relate to overall cardiovascular outcome in cardiomyopathies. A major role for cardiac MR imaging in cardiomyopathies is to identify myocardial scar for diagnostic and prognostic purposes.

  19. A fatal case of peripartum cardiomyopathy.

    PubMed

    Cohen, Ronny; Mallet, Thierry; Mirrer, Brooks; Loarte, Pablo; Gale, Michael; Kastell, Paul

    2014-06-01

    Peripartum cardiomyopathy is a life-threatening cardiac condition affecting pregnant women either late in pregnancy or early in the post-partum period. The latest studies show a dramatic improvement in the mortality rates of women affected with this disorder, which has been correlated with advances in medical therapy for heart failure. However, patients continue to die of this condition. The following case report describes a typical patient with peripartum cardiomyopathy diagnosed on clinical grounds, along with echocardiogram findings of severe systolic dysfunction and global hypokinesis consistent with dilated cardiomyopathy. Emergency cesarean delivery had to be performed for fetal distress. There was significant improvement of the patient's condition with standard pharmacological management for heart failure at the time of discharge. However, five weeks after discharge, fatal cardiac arrest occurred. It is hoped that this article will raise awareness about this rare but potentially fatal condition and promote understanding of its main clinical features, diagnostic criteria, and conventional pharmacological management.

  20. Dilated cardiomyopathy and progressive familial intrahepatic cholestasis

    PubMed Central

    James, Stephanie; Waterhouse, Deirdre; McDonald, Kenneth; O'Hanlon, Rory

    2014-01-01

    This case is of a 29-year-old man with progressive familial intrahepatic cholestasis type 1 also known as Byler's disease. At the age of 21, our patient developed non-ischaemic dilated cardiomyopathy. Cardiac MRI demonstrated global wall thinning, with significant areas of myocardial fibrosis in the mid and epicardial walls from base to apex on postgadolinium late contrast enhanced images. No shared genetic loci between dilated cardiomyopathy and Byler's or cholestatic liver disease have yet been found. This presents the first documented case of non-ischaemic dilated cardiomyopathy, with evidence of mid wall fibrosis, in association with an established diagnosis of progressive familial intrahepatic cholestasis type 1 since childhood. PMID:24654243

  1. Sheehan syndrome with reversible dilated cardiomyopathy.

    PubMed

    Laway, Bashir A; Alai, Mohammad S; Gojwari, Tariq; Ganie, Mohd A; Zargar, Abdul Hamid

    2010-01-01

    Cardiac abnormalities in patients with Sheehan syndrome are uncommon. A case of Sheehan syndrome with dilated cardiomyopathy is presented in whom hormone replacement with levothyroxine and prednisolone resulted in complete recovery of cardiomyopathy. A 25-year-old woman presented with lactation failure, secondary amenorrhea, features of hypothyroidism and a hypocortisol state following severe postpartum hemorrhage after her last child birth. She also had smear positive pulmonary tuberculosis. After starting antitubercular treatment, she developed shock, suggestive of hypocortisol crisis. Hormonal investigations revealed evidence of panhypopitutarism and magnetic resonance imaging revealed partial empty sella. Meanwhile echocardiography revealed evidence of dilated cardiomyopathy (DCM). The patient was given replacement therapy in the form of glucocorticoids and levothyroxine in addition to antitubercular treatment. She improved and on follow-up over a period of 7 months, the DCM completely reversed. To our knowledge this is the first report of reversible DCM in a patient with Sheehan syndrome.

  2. Cardiomyopathy from 1,1-Difluoroethane Inhalation.

    PubMed

    Kumar, Suwen; Joginpally, Tejaswini; Kim, David; Yadava, Mrinal; Norgais, Konchok; Laird-Fick, Heather S

    2016-10-01

    Consumer aerosol products can be inhaled for their psychoactive effects, but with attendant adverse health effects including "sudden sniffing death." Cardiomyopathy has rarely been described in association with 1,1-difluoroethane (DFE), a common aerosol propellant. We report a 33-year-old male who developed acute myocardial injury and global hypokinesis along with rhabdomyolysis, acute kidney injury, and fulminant hepatitis after 2 days' nearly continuous huffing. Workup for other causes, including underlying coronary artery disease, was negative. His cardiac function improved over time. The exact mechanism of DFE's effects is uncertain but may include catecholamine-induced cardiomyopathy, coronary vasospasm, or direct cellular toxicity.

  3. Two Cases of Stress Cardiomyopathy during Esophagogastroduodenoscopy

    PubMed Central

    Yu, Jong Won; Park, Jongha; Song, Pil Sang; Park, Jae Hyun; Kim, Min Sung; Jeon, Gi Jung; Kim, Min Sik; Kim, Tae Oh

    2016-01-01

    Esophagogastroduodenoscopy (EGD) is considered a relatively safe procedure. However, the procedure and the materials used in EGD with conscious sedation can cause stress to the patient. Adverse events during EGD have been reported, represented by cardiopulmonary complications. To date, five cases have reported worldwide to be associated with gastrointestinal endoscopy. Stress cardiomyopathy (SCMP) is a reversible cardiomyopathy that typically occurs in postmenopausal women due to stress and may resolve within a few weeks. SCMP resembles acute myocardial infarction but differs in terms of treatment and prognosis. Here, we describe two cases of SCMP with shock during EGD with conscious sedation. PMID:26855928

  4. Differentiating constrictive pericarditis from restrictive cardiomyopathy.

    PubMed

    Yazdani, Kambiz; Maraj, Suraj; Amanullah, Aman M

    2005-01-01

    Constrictive pericarditis and restrictive cardiomyopathy are 2 forms of diastolic dysfunction with similar presentation but different treatment options. Whereas constrictive pericarditis has the potential of being cured with pericardiectomy, restrictive cardiomyopathy is usually incurable. It is therefore crucial to differentiate between the 2 disorders. In the last few years, new diagnostic techniques have become available to differentiate these causes of diastolic dysfunction from each other. This review provides a complete, in-depth comparison of the 2 disorders with regard to their symptoms and clinical features, etiology, pathophysiology, hemodynamics, echocardiographic presentation, and finally the different available management options.

  5. Arrhythmogenic Noncompaction Cardiomyopathy: Is There an Echocardiographic Phenotypic Overlap of Two Distinct Cardiomyopathies?

    PubMed

    Aras, Dursun; Ozeke, Ozcan; Cay, Serkan; Ozcan, Firat; Baser, Kazım; Dogan, Umuttan; Unlu, Murat; Demirkan, Burcu; Tufekcioglu, Omac; Topaloglu, Serkan

    2015-09-01

    The clinical diagnosis of right ventricular (RV) cardiomyopathies is often challenging. It is difficult to differentiate the isolated left ventricular (LV) noncompaction cardiomyopathy (NC) from biventricular NC or from coexisting arrhythmogenic ventricular cardiomyopathy (AC). There are currently few established morphologic criteria for the diagnosis other than RV dilation and presence of excessive regional trabeculation. The gross and microscopic changes suggest pathological similarities between, or coexistence of, RV-NC and AC. Therefore, the term arrhythmogenic right ventricular cardiomyopathy is somewhat misleading as isolated LV or biventricular involvement may be present and thus a broader term such as AC should be preferred. We describe an unusual case of AC associated with a NC in a 27-year-old man who had a history of permanent pacemaker 7 years ago due to second-degree atrioventricular block.

  6. Aberrant Epicardial Adipose Tissue Extracellular Matrix Remodeling in Patients with Severe Ischemic Cardiomyopathy: Insight from Comparative Quantitative Proteomics

    PubMed Central

    Jiang, Ding-Sheng; Zeng, Hao-Long; Li, Rui; Huo, Bo; Su, Yun-Shu; Fang, Jing; Yang, Qing; Liu, Li-Gang; Hu, Min; Cheng, Cai; Zhu, Xue-Hai; Yi, Xin; Wei, Xiang

    2017-01-01

    There is ample evidence indicating that epicardial adipose tissue (EAT) volume and thickness is positively associated with coronary artery disease (CAD). However, the exact pathological changes in the human EAT after myocardial ischemia remains largely unclear. In the current study, we applied a comparative quantitative proteomics to elucidate the altered biological processes in the EAT of ischemic cardiomyopathy (ICM) patients. A total of 1649 proteins were successfully quantified in our study, among which 165 proteins were significantly changed (ratio <0.8 or >1.2 fold and p < 0.05 in both repetitions) in EAT of ICM individuals. Gene ontology (GO) enrichment analysis revealed that cardiac structure and cellular metabolism were over-represented among these regulated proteins. The hypertrophic cardiomyopathy, adrenergic signaling in cardiomyocytes, extracellular matrix (ECM)-receptor interaction, phagosome, Glycolysis/Gluconeogenesis, and PPAR signaling pathway were highlighted by the KEGG PATHWAY analysis. More importantly, we found that the proteins responsible for extracellular matrix organization were dramatically increased in EAT of ICM patients. In addition, the picrosirius red (PSR) staining results showed that the collagen fiber content was prominently increased, which indicated the EAT of ICM individuals underwent extracellular matrix remodeling and ERK1/2 activation maybe responsible for these pathological changes partially. PMID:28256566

  7. Platelet function in Takotsubo cardiomyopathy.

    PubMed

    Núñez-Gil, Iván J; Bernardo, Esther; Feltes, Gisela; Escaned, Javier; Mejía-Rentería, Hernán D; De Agustín, José Alberto; Vivas, David; Nombela-Franco, Luis; Jiménez-Quevedo, Pilar; Macaya, Carlos; Fernández-Ortiz, Antonio

    2015-05-01

    Takotsubo cardiomyopathy (TK) includes a transient left ventricular dysfunction without obstructive coronary disease, sometimes after stressful situations with elevated cathecolamines. Since catecholamines activate platelets we aimed to study the platelet influence in a TK setting. We included 32 patients with a TK diagnosis, 13 with an acute coronary syndrome (ACS) and 18 healthy volunteers. Once consent informed was obtained, blood samples were extracted and processed (at admission and after 3 months follow-up). Clinical, ecg, echocardiographic and angiographic features were thoroughly recorded.Previous treatment before admission was similar between groups. No differences were observed in clinical features or any of the acute markers studied regarding platelet reactivity between TK compared to ACS. After follow-up, aggregation levels and platelet reactivity showed differences, mainly due to the antithrombotic therapy prescribed at discharge, but similar to volunteers. Circulating epinephrine during the acute phase was significantly higher in TK (p < 0.001). Patients with higher levels of epinephrine had elevated platelet activation and aggregation after 3 months. No differences were observed in Takotsubo acute platelet aggregation compared to patients with ACS, in sp