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Hypertrophic Cardiomyopathy (hypertrophic + cardiomyopathy)
Kinds of Hypertrophic Cardiomyopathy Selected AbstractsNOVEL MITOCHONDRIAL DNA MUTATIONS ASSOCIATED WITH CHINESE FAMILIAL HYPERTROPHIC CARDIOMYOPATHYCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2009Yan-Ling Wei SUMMARY 1Hypertrophic cardiomyopathy (HCM) is a genetic disorder that has a complex set of symptoms and potentially devastating consequences. Increasing evidence indicates that mitochondrial DNA (mtDNA) mutations are responsible for the development of HCM, but the mtDNA mutations appear to differ considerably among different populations and regions. 2In the present study, three families with HCM were found and investigated: one in Shandong province and two in the Chongqing region of China. The entire mtDNA genome from the 18 affected and 66 unaffected family members was sequenced directly and the mtDNA mutations were determined. 3The frequency of haplogroup M10 was significantly higher in family members with HCM (HCM group) than in unaffected family members (normal group). Three mtDNA mutations were found with a significantly higher frequency in affected individuals than in unaffected family individuals, namely G7697A in the cytochrome c oxidase subunit II gene (P < 0.0001; odds ratio (OR) 227.5; 95% confidence interval (CI) 23.6,2194.8) and T12477C (P = 0.0037; OR 5.6; 95% CI 1.8,17.6) and G13135A in the NADH dehydrogenase 5 gene (P < 0.0001; OR 26.0; 95% CI 6.9,98.3), suggesting that these mutations are probably associated with susceptibility to HCM. In addition, mitochondrial Complex I activity was markedly decreased in the HCM group, suggesting that these mutations most likely affect mitochondrial respiratory function. 4In conclusion, the results of the present study imply that mtDNA mutations G7697A, T12477C and G13135A are genetic factors that indicate a susceptibility to HCM and that could be used for the large-scale screening of genetic markers as well as the early diagnosis of HCM. [source] GENES, CALCIUM AND MODIFYING FACTORS IN HYPERTROPHIC CARDIOMYOPATHYCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 1-2 2006Tatiana Tsoutsman SUMMARY 1Familial hypertrophic cardiomyopathy (FHC) is a primary disorder of the myocardium characterized by remarkable diversity in clinical presentations, ranging from no symptoms to severe heart failure and sudden cardiac death. 2Over the past 15 years, at least 11 genes have been identified, defects of which cause FHC. Most of these genes encode proteins that comprise the basic contractile unit of the heart (i.e. the sarcomere). 3Genetic studies are now beginning to have a major impact on the diagnosis in FHC, as well as in guiding treatment and preventative strategies. Although much is known about which genes cause disease, relatively little is known about the molecular steps leading from the gene defect to the clinical phenotype and what factors modify the expression of the mutant genes. 4Concurrent studies in cell culture and animal models of FHC are now beginning to shed light on the signalling pathways involved in FHC and the role of both environmental and genetic modifying factors. Calcium dysregulation appears to be important in the pathogenesis of FHC. 5Understanding these basic molecular mechanisms will ultimately improve our knowledge of the basic biology of heart muscle function and will therefore provide new avenues for diagnosis and treatment not only for FHC, but also for a range of human cardiovascular diseases. [source] Is Functional Capacity Related to Left Atrial Contractile Function in Nonobstructive Hypertrophic Cardiomyopathy?CONGESTIVE HEART FAILURE, Issue 5 2005Yukitaka Shizukuda MD The mechanisms underlying reduced exercise capacity in patients with nonobstructive hypertrophic cardiomyopathy (NHCM) could include perturbations of ventricular relaxation, diastolic compliance, or compensatory atrial systolic function. We hypothesized that a loss of atrial contractility in NHCM patients leads to reduced functional capacity. To test this hypothesis, we compared resting noninvasive left atrial ejection phase indices in 49 consecutive patients with NHCM (ages 36±10 years; 41% female) and normal left ventricular ejection fraction (mean, 68%±8%) with objective metabolic exercise parameters. Left atrial active emptying fraction, ejection force, and kinetic energy failed to predict exercise capacity. Only left atrial total and active emptying volumes correlated weakly with minute volume/CO2 production slope (r=0.31 and r=0.33; p<0.05 for both). Furthermore, when subjects were stratified by New York Heart Association symptomatology, exercise parameters,but not atrial contractility,differed between groups. These data, obtained at rest, fail to suggest that NHCM-related heart failure symptoms are due to an atrial myopathy. [source] Effect of Alcohol-Induced Septal Ablation on Left Atrial Volume and Ejection Fraction Assessed by Real Time Three-Dimensional Transthoracic Echocardiography in Patients with Hypertrophic CardiomyopathyECHOCARDIOGRAPHY, Issue 7 2008Fadi G. Hage M.D. Alcohol-induced septal ablation (AISA) is an accepted treatment for hypertrophic cardiomyopathy (HCM) patients with left ventricular (LV) outflow obstruction who are unresponsive to medical therapy. As left atrial (LA) enlargement has been correlated with increased morbidity and mortality in HCM, we assessed LA volumes and ejection fraction (EF) prior to and after AISA using real time three-dimensional (3D) transthoracic echocardiography (TTE) in 12 patients (9 women; mean age 52 ± 15 years; 11 Caucasian). All patients underwent successful AISA with no complications and their resting left ventricular outflow gradients decreased from 40.5 ± 22.2 to 9.1 ± 17.6 mmHg (P < 0.001) while their gradients with provocation decreased from 126.2 ± 31.7 to 21.8 ± 28.0 mmHg (P < 0.001). All patients showed improvements in their New York Heart Association (NYHA) functional class. Both the LA end-systolic (45.2 ± 12.9 to 37.2 ± 13.7 ml, P < 0.0001) and end-diastolic (79.6 ± 18.9 to 77.1 ± 18.6 ml, P = 0.001) volumes decreased after AISA. The LA EF increased from 43.1 ± 9.0 to 52.5 ± 8.8% (P = 0.001). The increase in LA EF correlated with the decrease in the resting left ventricular outflow gradient (R =,0.647, P = 0.03). In conclusion, 3D echocardiography can be utilized to follow LA function after AISA for HCM. AISA results in clinical improvement in patients with HCM and in improvement of LA EF that is correlated with the decrease in the left ventricular outflow gradient. [source] Clinical and Echocardiographic Aspects of Mid-Ventricular Hypertrophic CardiomyopathyECHOCARDIOGRAPHY, Issue 6 2005Francisco Martínez Baca-López M.D. Three cases of patients with hypertropic cardiomyopathy, apical aneurysm, and mid-ventricular obstruction are presented. Two patients were diagnosed first by two-dimensional and Doppler echocardiography, which showed mid-ventricular obliteration, characteristic hourglass image, and paradoxic jet flow. One patient with suboptimal echocardiogram was necessary to perform contrast echocardiogram. Clinical picture was characterized by angina and dyspnea. Thallium myocardial imaging revealed perfusion abnormalities in apical region, ischemia or necrosis. Cardiac catheterism showed mid-ventricular obliteration and significant intraventricular gradient and coronary arteries angiography without lesions. [source] Comparison of Coronary Flow Velocities Between Patients with Obstructive and Nonobstructive Type Hypertrophic Cardiomyopathy: Noninvasive Assessment by Transthoracic Doppler EchocardiographyECHOCARDIOGRAPHY, Issue 1 2005Seden Celik M.D. Background: We aimed to compare coronary flow velocity (CFV) measurements of patients with nonobstructive (NHCM) and obstructive hypertrophic cardiomyopathy (HOCM) by using transthoracic Doppler echocardiography (TTDE). Methods and Results: In 11 patients with NHCM and 26 with HOCM, CFV in the distal left anterior descending (LAD) coronary was measured by TTDE (3.5 MHz) under the guidance of color Doppler flow mapping in addition to standard 2D and Doppler echocardiography. The results were compared with 24 normal participants who had no evidence of cardiac disease. Peak diastolic velocity of LAD was also higher in NHCM and HOCM than controls (52 ± 14 cm/sec and 54 ± 20 cm/sec vs 41 ± 11 cm/sec, respectively, P < 0.01). The analysis of systolic velocities revealed abnormal flow patterns in 16 (61%) patients with HOCM (12 systolic-reversal flow and 4 no systolic flow) and 6 (54%) (5 reversal flow and 1 zero flow) patients with NHCM (,11 ± 30 cm/sec and ,13 ± 38 cm/sec, vs 24 ± 9 cm/sec, respectively, P < 0.001). Linear regression analysis demonstrated no correlation between intraventricular pressure gradient and coronary flow velocities in HOCM patients. However, there were significant positive and negative correlations between septal thickness and diastolic and systolic velocities, respectively (r = 0.50, P < 0.002, and r =,0.43, P < 0.005). Conclusion: We conclude that the coronary flow velocity abnormalities are independent from the type of hypertrophic cardiomyopathy. [source] Severe Intraventricular Diastolic Gradient Due to Hypertrophic Cardiomyopathy and Systolic Left Ventricular Midcavitary ObstructionECHOCARDIOGRAPHY, Issue 1 2005Albert Yuh-Jer Shen M.S. No abstract is available for this article. [source] Hypertrophic Cardiomyopathy: A Case of Symptomatic Japanese Type Apical Hypertrophic CardiomyopathyECHOCARDIOGRAPHY, Issue 6 2004Murat Meriç M.D. A 61-year-old male patient was hospitalized due to the exertional angina pectoris. A diagnosis of apical hypertrophic cardiomyopathy was made by ECG (electrocardiography), echocardiographic, and coronary angiographic findings. This case was reported and related literature was reviewed because of its similarity to Japanese type apical hypertrophic cardiomyopathy (AHCMP) cases rarely seen outside Asia. [source] Abnormal Diastolic Flow Demonstrated by Color M Mode Echocardiography in Hypertrophic Cardiomyopathy with Mid-Ventricular Cavity ObliterationECHOCARDIOGRAPHY, Issue 1 2004Timothy A. Mixon M.D. We report a case of a 55-year-old woman who presented with ventricular tachycardia and myocardial infarction. Investigations revealed no disease of the epicardial coronary arteries, but a diagnosis of hypertrophic cardiomyopathy with mid-cavitary dynamic obstruction was made. Detailed echocardiographic examination, including pulse-wave Doppler and Color M Mode recordings revealed unusual components of diastolic dysfunction. (ECHOCARDIOGRAPHY, Volume 21, January 2004) [source] Echocardiographic Diagnosis of Apical Hypertrophic Cardiomyopathy with Optison ContrastECHOCARDIOGRAPHY, Issue 6 2002Jagruti Patel M.D. We describe a case of obstructive apical hypertrophic cardiomyopathy in a 61-year-old Caucasian female with a history of chest pain syndrome. The patient was referred to the echo lab by her nuclear cardiologist, who was impressed by her abnormal stress nuclear perfusion scan that showed marked increased uptake of radioisotope at the left ventricular (LV) apex. The patient had deep negative T waves on her electrocardiogram similar to those originally described in the Japanese population. Transthoracic echocardiography with native harmonic imaging was suboptimal for visualizing LV segments. Therefore, 0.5 cc of Optison contrast was given intravenously, with repeat transthoracic imaging confirming the diagnosis. The patient and her family were referred for additional genetic testing and cardiovascular workup. [source] A Case Report of Surgical Septal Myectomy of Hypertrophic Cardiomyopathy With Concomitant Left Ventricular Outflow Tract and Mid-Ventricular ObstructionsJOURNAL OF CARDIAC SURGERY, Issue 6 2006Dr W. Williams No abstract is available for this article. [source] Substrate and Procedural Predictors of Outcomes After Catheter Ablation for Atrial Fibrillation in Patients with Hypertrophic CardiomyopathyJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 10 2008T. JARED BUNCH M.D. Background: Hypertrophic cardiomyopathy (HCM) is often accompanied by atrial fibrillation (AF) due to diastolic dysfunction, elevated left atrial pressure, and enlargement. Although catheter ablation for drug-refractory AF is an effective treatment, the efficacy in HCM remains to be established. Methods: Thirty-three consecutive patients (25 male, age 51 ± 11 years) with HCM underwent pulmonary vein (PV) isolation (n = 8) or wide area circumferential ablation with additional linear ablation (n = 25) for drug-refractory AF. Twelve-lead and 24-hour ambulating ECGs, echocardiograms, event monitor strips, and SF 36 quality of life (QOL) surveys were obtained before ablation and for routine follow-up. Results: Twenty-one (64%) patients had paroxysmal AF and 12 (36%) had persistent/permanent AF for 6.2 ± 5.2 years. The average ejection fraction was 0.63 ± 0.12. The average left atrial volume index was 70 ± 24 mL/m2. Over a follow-up of 1.5 ± 1.2 years, 1-year survival with AF elimination was 62%(Confidence Interval [CI]: 66-84) and with AF control was 75%(CI: 66-84). AF control was less likely in patients with a persistent/chronic AF, larger left atrial volumes, and more advanced diastolic disease. Additional linear ablation may improve outcomes in patient with severe left atrial enlargement and more advanced diastolic dysfunction. Two patients had a periprocedureal TIA, one PV stenosis, and one died after mitral valve replacement from prosthetic valve thrombosis. QOL scores improved from baseline at 3 and 12 months. Conclusion: Outcomes after AF ablation in patients with HCM are favorable. Diastolic dysfunction, left atrial enlargement, and AF subtype influence outcomes. Future studies of rhythm management approaches in HCM patients are required to clarify the optimal clinical approach. [source] Defibrillator Therapies in Hypertrophic Cardiomyopathy: Too Many Swings at Bad Pitches?JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 5 2007SUSAN S. KIM M.D. [source] Resynchronization or Dyssynchronization,Successful Treatment with Biventricular Stimulation of a Child with Obstructive Hypertrophic Cardiomyopathy without DyssynchronyJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 5 2007LENARCZYK RADOSLAW M.D. CRT in a Child with Hypertrophic Cardiomyopathy. We present a case of a 10-year-old boy with hypertrophic cardiomyopathy, intraventricular pressure gradient of 104 mmHg, and indications for prophylactic ICD implantation. Based on intraoperative pressure measurements, the child was implanted with biventricular ICD. During 2.5 months of observation, the patient's functional status improved significantly, as shown by subjective and objective parameters and, moreover, the pressure gradient fell to 12 mmHg. Significant electrical and mechanical cardiac dyssynchrony appeared parallel to clinical improvement. [source] Predictors of Complete Heart Block After Alcohol Septal Ablation for Hypertrophic Cardiomyopathy and the Timing of Pacemaker ImplantationJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 1 2007F.R.A.C.P., SEIFEDDIN S. EL-JACK M.B.B.S. Catheter-based alcohol septal ablation has recently been introduced for the treatment of left ventricular outflow tract obstruction in hypertrophic obstructive cardiomyopathy. It is associated with various conduction disturbances and may lead to transient or persistent complete heart block (CHB). Electrocardiographic (ECG) changes and predictors of developing CHB and the timing of permanent pacemaker implantation have been variable among the different studies. Among 50 patients studied, we found that a new right bundle branch pattern was the most common new ECG change after septal ablation and that baseline left bundle branch block was strongly associated with the development of CHB (P = 0.004); 9 patients (18%) required permanent pacemaker implantation of whom 7 (78%) remained pacemaker dependent at 14 days with no delayed recovery of atrioventricular conduction. This favors an early pacemaker implantation strategy. [source] Cardiac Troponin I in Feline Hypertrophic CardiomyopathyJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 5 2002William E. Hemdon Measurement of plasma cardiac troponin I concentration ([cTnI]) is a sensitive and specific means for detecting myocardial damage in many mammalian species. Studies have shown that [cTnI] increases rapidly after cardiomyocyte injury. The molecular structure of cTnl is highly conserved across species, and current assays developed for its detection in humans have been validated in many species. In this study, [cTnI] was quantified using a 2-site sandwich assay in plasma of healthy control cats (n = 33) and cats with moderate to severe hypertrophic cardiomyopathy (HCM) (n = 20). [cTnI] was significantly higher in cats with HCM (median, 0.66 ng/mL; range, 0.05,10.93 ng/mL) as compared with normal cats (median, <0.03 ng/mL; range, <0.03-0.16 ng/mL) (P < .0001). An increase in [cTnI] was also highly sensitive (sensitivity = 85%) and specific (specificity = 97%) for differentiating cats with moderate to severe HCM from normal cats. [cTnI] was weakly correlated with diastolic thickness of the left ventricular free wall (r2= .354; P= .009) but not with the diastolic thickness of the interventricular septum (P= .8467) or the left atrium: aorta ratio (P= .0652). Furthermore, cats with congestive heart failure at the time of cTnl analysis had a significantly higher [cTnI] than did cats that had never had heart failure and those whose heart failure was controlled at the time of analysis (P= .0095 and P= .0201, respectively). These data indicate that cats with HCM have ongoing myocardial damage. Although the origin of this damage is unknown, it most likely explains the replacement fibrosis that is consistently identified in cats with moderate to severe HCM. [source] Emotional Stress Triggers Symptoms in Hypertrophic Cardiomyopathy: A Survey of the Hypertrophic Cardiomyopathy AssociationPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 9 2010RACHEL LAMPERT M.D. Background:,Symptoms are among the most important factors impacting quality of life (QOL) in hypertrophic cardiomyopathy (HCM) patients, and reflect a poor prognosis. Whether emotional stress can trigger symptoms of chest pain, dyspnea, palpitations, and lightheadedness has not been described. Methods:,Members of the Hypertrophic Cardiomyopathy Association (HCMA) received an electronic link via e-mail to an ongoing online survey, also accessed via links on the HCMA message-board and homepage. Between May 2007 and November 2008, there were 1,297 respondents. The survey queried demographic and self-reported clinical information, and types and triggers of symptoms. Respondents reported physical and emotional QOL on a 1,10 Likert scale. Results:,Symptoms reported included chest pain (49%), dyspnea (70%), palpitations (61%), and syncope/lightheadedness (59%). The most common symptom trigger was exertion, 64% describing symptoms while climbing stairs or hills. Forty-nine percent described experiencing symptoms during emotional stress. Those reporting chest pain were more likely to report emotion triggering (60%) than those reporting palpitations, syncope/lightheadedness, or dyspnea (50,54% each). Both physical and emotional QOL were significantly decreased in those describing emotion-triggered symptoms. Women were more likely than men to report symptoms overall, as well as emotion-triggered symptoms (50% vs 35%, P < 0.001) and exertion-triggered symptoms (79% vs 58%, P < 0.001). After controlling for presence of symptoms, both emotion- and exertion-triggered symptoms remained significantly more common in women. Conclusions:,Triggering of symptoms by emotion is common in individuals with HCM. Further studies will determine pathways linking emotional stressors with chest pain, dyspnea, palpitations, and lightheadedness in these patients. (PACE 2010; 33:1047,1053) [source] Supraventricular Arrhythmia Induction by an Implantable Cardioverter Defibrillator in a Patient with Hypertrophic CardiomyopathyPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 3 2010FARIBORZ AKBARZADEH M.D. A 23-year-old woman with obstructive hypertrophic cardiomyopathy and history of frequent unexplained syncope had undergone implantable cardioverter defibrillator implantation. She had experienced frequent inappropriate shocks since implantation due to T-wave oversensing. After one of the syncopal attacks, she was found to have an atrioventricular (AV)-reentrant tachycardia, induced by a high-voltage shock, with rapid degeneration to atrial fibrillation and then ventricular fibrillation. The AV-reentrant tachycardia was believed to be the cause of both syncopal attacks and inappropriate shocks. The patient has been asymptomatic after ablation of the accessory pathway. To the best of our knowledge, this is the first report of induction of an AV-reentrant tachycardia by a high-voltage implantable cardioverter defibrillator shock. (PACE 2010; 33:372,376) [source] Analysis of the Corrected QT Before the Onset of Nonsustained Ventricular Tachycardia in Patients with Hypertrophic CardiomyopathyPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 1p2 2003BARANOWSKI BARANOWSKI, R., et al.: Analysis of the Corrected QT Before the Onset of Nonsustained Ventricular Tachycardia in Patients with Hypertrophic Cardiomyopathy. This study examined ventricular repolarization before the onset of 37 episodes of nonsustained ventricular tachycardia (NSVT) in 26 untreated patients with hypertrophic cardiomyopathy (HCM). Fourteen episodes were recorded in patients with a history of cardiac arrest or patients who died suddenly during follow-up. The QT interval was measured beat-by-beat on 24-hour ambulatory electrocardiograms. Mean 24-hour, hourly QTc and QTc of the last 10 beats prior to NSVT, consisted of 4,50 cycles (mean9 ± 10), at the fastest rates of 100,175 beats/min (mean 122 ± 22) were analyzed. NSVT was more prevalent during nighttime (23 episodes), than during daytime (14 episodes,P < 0.05). No significant differences were observed between mean 24-hour, mean hourly QTc during the hour with NSVT, and QTc of the last 10 cycles prior to onset of NSVT. QTc was significantly longer in patients with a history of sudden cardiac death (SCD) or who died suddenly during follow-up than in survivors. The 24-hour QT variability was higher in nonsurvivors than in survivors ( -39 ± 6vs33 ± 6 ms, P = 0.03). Episodes of NSVT in untreated patients with hypertrophic cardiomyopathy were more frequent during the nighttime. The 24-hour QT variability was higher in nonsurvivors than in survivors. (PACE 2003; 26[Pt. II]:387,389) [source] ST Segment "Hump" during Exercise Testing and the Risk of Sudden Cardiac Death in Patients with Hypertrophic CardiomyopathyANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 2 2009Andreas P. Michaelides M.D., F.A.C.C., F.E.S.C. Background: The appearance of a discrete upward deflection of the ST segment termed "the ST hump sign" (STHS) during exercise testing has been associated with resting hypertension and exaggerated blood pressure response to exercise. Objective: We investigated the prevalence and clinical significance of this sign in a population of patients with hypertrophic cardiomyopathy. Methods: Eighty-one patients with hypertrophic cardiomyopathy (HCM) who underwent cardiopulmonary exercise testing were followed in a retrospective cohort study for a mean period of 5.3 years. Results: The appearance of the STHS at the peak of exercise testing was observed in 42 patients (52%), particularly in the inferior and the lateral leads. Patients with the STHS had higher fractional shortening and maximum left ventricular wall thickness and exhibited more frequently outflow tract gradient >30 mmHg at rest. Furthermore, the presence of STHS was a strong independent predictor of the risk of sudden cardiac death (SCD), as the latter occurred in eight of the patients with this sign (8/42, 19%) and in none of the patients without it (0/39, 0%) (P < 0.001). Conclusion: The appearance of a "hump" at the ST segment during exercise testing appears to be a risk factor for SCD in patients with HCM. However, further studies are necessary to validate this finding in larger populations and to elucidate the mechanism of the appearance of the "hump." [source] Impact of QT Variables on Clinical Outcome of Genotyped Hypertrophic CardiomyopathyANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 1 2009Katsuharu Uchiyama M.D. Background: Although QT variables such as its interval and/or dispersion can be clinical markers of ventricular tachyarrhythmia, few data exist regarding the role of QT variables in genotyped hypertrophic cardiomyopathy (HCM). Therefore, we analyzed QT variables in genotyped subjects with or without left ventricular hypertrophy (LVH). Methods: QT variables were analyzed in 111 mutation and 43 non-mutation carriers who were divided into three groups: A, those without ECG abnormalities and echocardiographically determined LVH (wall thickness ,13 mm); B, those with ECG abnormalities but LVH; and C, those with ECG abnormalities and LVH. We also examined clinical outcome of enrolled patients. Results: Maximal LV wall thickness in group C (19.0 ± 4.3 mm, mean ±SD) was significantly greater than that in group A (9.2 ± 1.8) and group B (10.4 ± 1.8). Under these conditions, maximum QTc interval and QT dispersion were significantly longer in group C than those in group A (438 ± 38 ms vs 406 ± 30 and 64 ± 31 vs 44 ± 18, respectively; P < 0.05). QTc interval and QT dispersion in group B (436 ± 50 and 64 ± 22 ms) were also significantly greater than those in group A. During follow-up periods, four sudden cardiac deaths and one ventricular fibrillation were observed in group C, and two nonlethal ventricular tachyarrhythmias were observed in group B. Conclusions: Patients with HCM-related gene mutation accompanying any ECG abnormalities frequently exhibited impaired QT variables even without LVH. We suggest that careful observation should be considered for those genotyped subjects. [source] Variability of Left Ventricular Outflow Tract Gradient in Hypertrophic CardiomyopathyCLINICAL CARDIOLOGY, Issue 10 2009Petkow Dimitrow MD No abstract is available for this article. [source] Apical Aneurysm Formation in Hypertrophic Cardiomyopathy with Mid-ventricular ObstructionCLINICAL CARDIOLOGY, Issue 7 2009Satoshi Kurisu M.D. No abstract is available for this article. [source] Hypertrophic cardiomyopathy: from genetics to treatmentEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 4 2010Ali J. Marian Eur J Clin Invest 2010; 40 (4): 360,369 Abstract Background, Hypertrophic cardiomyopathy (HCM) is the prototypic form of pathological cardiac hypertrophy. HCM is an important cause of sudden cardiac death in the young and a major cause of morbidity in the elderly. Design, We discuss the clinical implications of recent advances in the molecular genetics of HCM. Results, The current diagnosis of HCM is neither adequately sensitive nor specific. Partial elucidation of the molecular genetic basis of HCM has raised interest in genetic-based diagnosis and management. Over a dozen causal genes have been identified. MYH7 and MYBPC3 mutations account for about 50% of cases. The remaining known causal genes are uncommon and some are rare. Advances in DNA sequencing techniques have made genetic screening practical. The difficulty, particularly in the sporadic cases and in small families, is to discern the causal from the non-causal variants. Overall, the causal mutations alone have limited implications in risk stratification and prognostication, as the clinical phenotype arises from complex and often non-linear interactions between various determinants. Conclusions, The clinical phenotype of ,HCM' results from mutations in sarcomeric proteins and subsequent activation of multiple cellular constituents including signal transducers. We advocate that HCM, despite its current recognition and management as a single disease entity, involves multiple partially independent mechanisms, despite similarity in the ensuing phenotype. To treat HCM effectively, it is necessary to delineate the underlying fundamental mechanisms that govern the pathogenesis of the phenotype and apply these principles to the treatment of each subset of clinically recognized HCM. [source] Actin mutations in hypertrophic and dilated cardiomyopathy cause inefficient protein folding and perturbed filament formationFEBS JOURNAL, Issue 8 2005Søren Vang Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are the most common hereditary cardiac conditions. Both are frequent causes of sudden death and are often associated with an adverse disease course. Alpha-cardiac actin is one of the disease genes where different missense mutations have been found to cause either HCM or DCM. We have tested the hypothesis that the protein-folding pathway plays a role in disease development for two actin variants associated with DCM and six associated with HCM. Based on a cell-free coupled translation assay the actin variants could be graded by their tendency to associate with the chaperonin TCP-1 ring complex/chaperonin containing TCP-1 (TRiC/CCT) as well as their propensity to acquire their native conformation. Some variant proteins are completely stalled in a complex with TRiC and fail to fold into mature globular actin and some appear to fold as efficiently as the wild-type protein. A fraction of the translated polypeptide became ubiquitinated and detergent insoluble. Variant actin proteins overexpressed in mammalian cell lines fail to incorporate into actin filaments in a manner correlating with the degree of misfolding observed in the cell-free assay; ranging from incorporation comparable to wild-type actin to little or no incorporation. We propose that effects of mutations on folding and fiber assembly may play a role in the molecular disease mechanism. [source] Hypertrophic cardiomyopathy in the elderlyGERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 1 2010Toru Kubo Hypertrophic cardiomyopathy (HCM) is a relatively common genetic cardiac disorder with heterogeneous morphological, functional and clinical features. Although the risk of sudden death and incapacitating symptoms in young patients has been focused upon, the disease has been found with increasing frequency in elderly patients. However, there have been few studies on clinical features of HCM in the elderly. We established a cardiomyopathy registration study in Kochi Prefecture, which is one of the most aged communities in Japan, to provide detailed descriptions of the clinical features of HCM in a community-based patient cohort. The unselected regional HCM population consisted largely of elderly patients (70% of the study cohort being ,60 years of age at registration), although HCM has been regarded largely as a disease of the young. Cardiac hypertrophy that becomes clinically apparent late in life can be a genetic disorder, and mutations in the cardiac myosin-binding protein C gene are the most common cause of late-onset or elderly HCM. In the morphological features, sarcomere gene defects seem to have a predilection for a crescent-shaped left ventricular cavity with reversed septal curvature even in elderly patients, although an ovoid left ventricular shape was frequently seen in elderly patients in previous clinical studies on morphological characteristics of HCM. In middle-aged or elderly patients with HCM, heart failure and embolic events, which were strongly associated with atrial fibrillation, were very important. It is important to manage HCM patients from the standpoint of longitudinal evolution in order to prevent those clinical complications. [source] Substrate and Procedural Predictors of Outcomes After Catheter Ablation for Atrial Fibrillation in Patients with Hypertrophic CardiomyopathyJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 10 2008T. JARED BUNCH M.D. Background: Hypertrophic cardiomyopathy (HCM) is often accompanied by atrial fibrillation (AF) due to diastolic dysfunction, elevated left atrial pressure, and enlargement. Although catheter ablation for drug-refractory AF is an effective treatment, the efficacy in HCM remains to be established. Methods: Thirty-three consecutive patients (25 male, age 51 ± 11 years) with HCM underwent pulmonary vein (PV) isolation (n = 8) or wide area circumferential ablation with additional linear ablation (n = 25) for drug-refractory AF. Twelve-lead and 24-hour ambulating ECGs, echocardiograms, event monitor strips, and SF 36 quality of life (QOL) surveys were obtained before ablation and for routine follow-up. Results: Twenty-one (64%) patients had paroxysmal AF and 12 (36%) had persistent/permanent AF for 6.2 ± 5.2 years. The average ejection fraction was 0.63 ± 0.12. The average left atrial volume index was 70 ± 24 mL/m2. Over a follow-up of 1.5 ± 1.2 years, 1-year survival with AF elimination was 62%(Confidence Interval [CI]: 66-84) and with AF control was 75%(CI: 66-84). AF control was less likely in patients with a persistent/chronic AF, larger left atrial volumes, and more advanced diastolic disease. Additional linear ablation may improve outcomes in patient with severe left atrial enlargement and more advanced diastolic dysfunction. Two patients had a periprocedureal TIA, one PV stenosis, and one died after mitral valve replacement from prosthetic valve thrombosis. QOL scores improved from baseline at 3 and 12 months. Conclusion: Outcomes after AF ablation in patients with HCM are favorable. Diastolic dysfunction, left atrial enlargement, and AF subtype influence outcomes. Future studies of rhythm management approaches in HCM patients are required to clarify the optimal clinical approach. [source] Fibrosis in heart disease: understanding the role of transforming growth factor-,1 in cardiomyopathy, valvular disease and arrhythmiaIMMUNOLOGY, Issue 1 2006Razi Khan Summary The importance of fibrosis in organ pathology and dysfunction appears to be increasingly relevant to a variety of distinct diseases. In particular, a number of different cardiac pathologies seem to be caused by a common fibrotic process. Within the heart, this fibrosis is thought to be partially mediated by transforming growth factor-,1 (TGF-,1), a potent stimulator of collagen-producing cardiac fibroblasts. Previously, TGF-,1 had been implicated solely as a modulator of the myocardial remodelling seen after infarction. However, recent studies indicate that dilated, ischaemic and hypertrophic cardiomyopathies are all associated with raised levels of TGF-,1. In fact, the pathogenic effects of TGF-,1 have now been suggested to play a major role in valvular disease and arrhythmia, particularly atrial fibrillation. Thus far, medical therapy targeting TGF-,1 has shown promise in a multitude of heart diseases. These therapies provide great hope, not only for treatment of symptoms but also for prevention of cardiac pathology as well. As is stated in the introduction, most reviews have focused on the effects of cytokines in remodelling after myocardial infarction. This article attempts to underline the significance of TGF-,1 not only in the post-ischaemic setting, but also in dilated and hypertrophic cardiomyopathies, valvular diseases and arrhythmias (focusing on atrial fibrillation). It also aims to show that TGF-,1 is an appropriate target for therapy in a variety of cardiovascular diseases. [source] Is Functional Capacity Related to Left Atrial Contractile Function in Nonobstructive Hypertrophic Cardiomyopathy?CONGESTIVE HEART FAILURE, Issue 5 2005Yukitaka Shizukuda MD The mechanisms underlying reduced exercise capacity in patients with nonobstructive hypertrophic cardiomyopathy (NHCM) could include perturbations of ventricular relaxation, diastolic compliance, or compensatory atrial systolic function. We hypothesized that a loss of atrial contractility in NHCM patients leads to reduced functional capacity. To test this hypothesis, we compared resting noninvasive left atrial ejection phase indices in 49 consecutive patients with NHCM (ages 36±10 years; 41% female) and normal left ventricular ejection fraction (mean, 68%±8%) with objective metabolic exercise parameters. Left atrial active emptying fraction, ejection force, and kinetic energy failed to predict exercise capacity. Only left atrial total and active emptying volumes correlated weakly with minute volume/CO2 production slope (r=0.31 and r=0.33; p<0.05 for both). Furthermore, when subjects were stratified by New York Heart Association symptomatology, exercise parameters,but not atrial contractility,differed between groups. These data, obtained at rest, fail to suggest that NHCM-related heart failure symptoms are due to an atrial myopathy. [source] AMP-activated protein kinase: a core signalling pathway in the heartACTA PHYSIOLOGICA, Issue 1 2009A. S. Kim Abstract Over the past decade, AMP-activated protein kinase (AMPK) has emerged as an important intracellular signalling pathway in the heart. Activated AMPK stimulates the production of ATP by regulating key steps in both glucose and fatty acid metabolism. It has an inhibitory effect on cardiac protein synthesis. AMPK also interacts with additional intracellular signalling pathways in a coordinated network that modulates essential cellular processes in the heart. Evidence is accumulating that AMPK may protect the heart from ischaemic injury and limit the development of cardiac myocyte hypertrophy to various stimuli. Heart AMPK is activated by hormones, cytokines and oral hypoglycaemic drugs that are used in the treatment of type 2 diabetes. The tumour suppressor LKB1 is the major regulator of AMPK activity, but additional upstream kinases and protein phosphatases also contribute. Mutations in the regulatory ,2 subunit of AMPK lead to an inherited syndrome of hypertrophic cardiomyopathy and ventricular pre-excitation, which appears to be due to intracellular glycogen accumulation. Future research promises to elucidate the molecular mechanisms responsible for AMPK activation, novel downstream AMPK targets, and the therapeutic potential of targeting AMPK for the prevention and treatment of myocardial ischaemia or cardiac hypertrophy. [source] | |||||||||||||||||||||||||||||||