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Hypertrophic cardiomyopathy (HC) is the most common genetic heart disease and an important cause of sudden death and heart failure symptoms. The current prevalence for HC (1:500) is based on echocardiographic population studies in which a substantial proportion of affected subjects have not come to clinical recognition. Therefore, we sought to define the subset of patients with HC who are diagnosed in the US. A proprietary integrated claims database including medical condition International Classification of Diseases, Ninth Revision diagnostic codes for over 160 million individual patients in the US was interrogated for 2013 to identify the prevalence of clinically recognized HC. Patients with ≥1 claim for any of the HC International Classification of Diseases, Ninth Revision diagnosis codes from January to December 2013 were identified. The combined occurrence rate of HC was stratified by age and gender and multiplied by the 2013 United States population in the same age/gender categories to produce the final projected prevalence. The analysis was performed on 169,089,614 patients, of whom 59,009 unique patients were identified with ≥1 claim for HC. The projected estimated occurrence of diagnosed HC in the US in 2013 was 1:3,195 for a total of 98,958 subjects. Average age at HC diagnosis was in the fifth decade of life, with 43% of the cohort composed of women. In conclusion, leveraging a claims-based data analytic technique, about 100,000 patients are diagnosed clinically with HC in the US, an occurrence which is less than the prevalence reported in systematic population studies based on echocardiographic diagnosis. This observation supports the view that many patients with HC are undiagnosed throughout life and enhances our understanding of the burden of this genetic heart disease on the health care system. [ABSTRACT FROM AUTHOR]

Identification of hypertrophic cardiomyopathy (HC) in young athletes is challenging when left ventricular (LV) wall thickness is between 13 and 15 mm. The aim of this study was to revise the ability of simple echocardiographic and clinical variables for the differential diagnosis of HC versus athlete's heart. Twenty-eight athletes free of cardiovascular disease were compared with 25 untrained patients with HC, matched for LV wall thickness (13 to 15 mm), age, and gender. Clinical, electrocardiographic, and echocardiographic variables were compared. Athletes had larger LV cavities (60 ± 3 vs 45 ± 5 mm, p <0.001), aortic roots (34 ± 3 vs 30 ± 3 mm, p <0.001), and left atria (42 ± 4 vs 33 ± 5 mm, p <0.001) than patients with HC. LV cavity <54 mm distinguished HC from athlete's heart with the highest sensitivity and specificity (both 100%, p <0.001). Left atrium >40 mm excluded HC with sensitivity of 92% and specificity of 71% (p <0.001). Athletes showed higher e' velocity by tissue Doppler imaging than patients with HC (12.5 ± 1.9 vs 9.3 ± 2.3 cm/second, p <0.001), with values <11.5 cm/second yielding sensitivity of 81% and specificity of 61% for the diagnosis of HC (p <0.001). Absence of diffuse T-wave inversion on electrocardiography (specificity 92%) and negative family history for HC (specificity 100%) also proved useful for excluding HC. In conclusion, in athletes with LV hypertrophy in the "gray zone" with HC, LV cavity size appears the most reliable criterion to help in diagnosis, with a cut-off value of <54 mm useful for differentiation from athlete's heart. Other criteria, including LV diastolic dysfunction, absence of T-wave inversion on electrocardiography, and negative family history, further aid in the differential diagnosis. [ABSTRACT FROM AUTHOR]

Almost one third of patients with hypertrophic cardiomyopathy (HC) will have an abnormal blood pressure response (ABPR) to exercise, and this has been associated with a greater risk of sudden cardiac death. In the present study, we examined the association between the steady (mean arterial pressure) and pulsatile (pulse pressure) blood pressure components as they relate to ABPR in patients with HC (n = 70). All patients completed a standard Bruce protocol during symptom-limited stress testing with concurrent hemodynamic measurements. Pulse pressure (PP) was significantly greater in patients with HC with an ABPR (n = 19) than in the patients with HC without an ABPR to exercise (p <0.05). According to binary logistic regression analysis, PP at rest was a significant predictor of ABPR in patients with HC (p <0.05). Mean arterial pressure was not significantly different between the 2 groups, nor was it a predictor of an ABPR in the presence of HC. Those within the greatest tertile of PP at rest were 4.8 times more likely to have an ABPR than those within the lowest PP tertile (95% confidence interval 1.24 to 18.2, p <0.05). In conclusion, elevations in PP at rest might identify patients with HC at a greater risk of having an ABPR during exercise. [ABSTRACT FROM AUTHOR]

Two patients with hypertrophic cardiomyopathy are reported from the recent experience of the Hypertrophic Cardiomyopathy Center of the Minneapolis Heart Institute Foundation, demonstrating limitations in the risk stratification algorithm currently used for this disease. One patient, an asymptomatic 21-year-old male college student, was prophylactically implanted with a cardioverter-defibrillator. This decision was based largely on the presence of apparent extensive myocardial fibrosis identified by contrast-enhanced cardiovascular magnetic resonance imaging, currently not considered a risk factor in this disease. Fifteen months later, ventricular fibrillation was interrupted by an appropriate defibrillator shock. The other patient, an asymptomatic 15-year-old male subject without any apparent high-risk markers, died suddenly at home. Necropsy examination of the heart identified scarring confined to portions of both left ventricular papillary muscles, possibly representing a substrate for ventricular tachyarrhythmias. In conclusion, these 2 cases demonstrate that present strategies for assessing high-risk status in hypertrophic cardiomyopathy are inadequate to identify all such patients. However, while the anecdotal nature of these observations cannot yet justify altering the general guidelines for implantation of defibrillators for the primary prevention of sudden death related to hypertrophic cardiomyopathy, 1 of our 2 cases suggests a future role for contrast-enhanced cardiovascular magnetic resonance in the risk stratification of this complex disease. [Copyright &y& Elsevier]

The aim of this study was to assess, using cardiovascular magnetic resonance (CMR), whether morphologic right ventricular (RV) abnormalities are present in patients with hypertrophic cardiomyopathy (HC). Left ventricular hypertrophy has been considered the predominant phenotypic expression of HC. Whether structural abnormalities of the right ventricle are also present in HC is unknown. CMR provides complete coverage of both ventricles with high spatial resolution. CMR was applied to study RV morphology in HC. CMR was performed on 46 subjects with HC (mean age 39 ± 16 years; 70% men) free of pulmonary hypertension and 22 healthy subjects (mean age 44 ± 16 years; 50% men). Mass, wall thickness, chamber volume, the ejection fraction, and fibrosis were assessed for both ventricles. Maximum RV wall thickness was increased in patients with HC compared with referent controls (7 ± 2 vs 5 ± 1 mm, p <0.001), including 15 (33%) with maximum wall thicknesses ≥8 mm (≥2 SDs higher than the mean for controls) and 4 (9%) with extreme hypertrophy (≥10 mm). RV hypertrophy was predominantly a diffuse process involving the entire or a significant proportion of the RV wall in most patients (n = 8 [53%]). The RV wall mass index was also increased in patients with HC (28 ± 9 vs 22 ± 4 g, p <0.001). A significant correlation was found between maximum RV and left ventricular wall thickness (R2 = 0.4, p <0.001) and between RV and left ventricular mass (R2 = 0.4, p <0.001). Only 1 (2%) patient with HC had evidence of RV wall fibrosis. In conclusion, morphologic RV abnormalities are present in a substantial proportion of patients with HC. [Copyright &y& Elsevier]

In hypertrophic cardiomyopathy (HC), an important subgroup of patients develop progressive and disabling symptoms that are related to heart failure and death. Although a direct relation has been demonstrated between left ventricular (LV) wall thickness and likelihood of sudden and unexpected death (usually in patients who are asymptomatic or mildly symptomatic), it is unresolved whether magnitude of hypertrophy is similarly associated with severity of heart failure. To determine the relation of LV wall thickness to heart failure symptoms in HC, 700 consecutive patients who had HC were assessed by 2-dimensional echocardiography. The relation between maximum level of heart failure symptoms by New York Heart Association functional class and maximum LV wall thickness was not linear but rather parabolic. Therefore, marked symptoms were most commonly associated with moderate degrees of LV hypertrophy (wall thickness 16 to 24 mm; 27%) but less frequently with extreme hypertrophy (≥30 mm 13%) or mild hypertrophy (≤15 mm; 19%, p = 0.0001). Mean New York Heart Association functional class showed a similar pattern with respect to moderate hypertrophy (1.9 ± 0.8), mild hypertrophy (1.6 ± 0.9), and extreme hypertrophy (1.6 ± 0.7, p = 0.005). Multivariable regression analysis showed the parabolic relation between heart failure symptoms and magnitude of LV hypertrophy to be independent of other hypertrophic cardiomyopathy related clinical variables. In conclusion, no direct relation was evident between symptoms of heart failure and magnitude of LV wall thickness, with implications for the natural history of HC. [Copyright &y& Elsevier]

Patients with left ventricular apical aneurysms represent a unique patient subgroup in the broad clinical spectrum of hypertrophic cardiomyopathy (HC) associated with the risk for sudden death, heart failure, and peripheral thromboembolism. Routine chronic anticoagulation has not been a standard recommendation for these patients. We present a 36-year-old patient with HC with features of acute coronary syndrome, likely secondary to coronary thromboembolism as a complication of left ventricular apical aneurysm. Our experience with this patient raises consideration for prophylactic anticoagulant therapy for this unusual subset of patients with HC. [ABSTRACT FROM AUTHOR]

The article presents a case study related to cardiac transplantation for treating the heart disease hypertropic cardiomyopathy (HC). It discusses case of the two family members who are suffering from the HC and had different phenotypic expressions. It explains that the symptoms of HC vary among patients and the patients with HC have very little gadolinium enhancement. It further mentions that there is a lack of relation between genotype and phenotype of diseases.

The investigators report similar phenotypes of hypertrophic cardiomyopathy with left ventricular apical aneurysm and thrombus in 2 brothers aged 8 years apart. This report highlights the genetic predisposition for this unique, high-risk phenotype, the issue of prophylactic anticoagulation, and the importance of nonstandard echocardiographic imaging views in the assessment of these patients. [ABSTRACT FROM AUTHOR]

Cardiovascular magnetic resonance (CMR) is a high spatial resolution, 3-dimensional tomographic imaging technique which may identify regions of massive left ventricular hypertrophy (particularly when confined to the anterolateral free wall) in which the extent of wall thickness is underestimated with traditional 2-dimensional echocardiography in patients with hypertrophic cardiomyopathy (HC). This observation may have potential implications on management strategies as extreme left ventricular hypertrophy is a primary risk factor for sudden death in HC and therefore supports an expanding role for CMR in the evaluation of HC patients. [Copyright &y& Elsevier]

In hypertrophic cardiomyopathy (HC), atrial fibrillation (AF) is an important determinant of clinical deterioration due to heart failure or embolic stroke. This study characterizes left atrial (LA) structural and functional parameters to establish markers predictive of AF risk, using cardiovascular magnetic resonance (CMR) imaging. We studied 427 consecutive patients with HC in sinus rhythm with CMR (age 44 ± 18 years), including 41 who developed clinically overt AF after study entry (2.6 ± 2.1 years), 49 patients with AF before CMR, 337 patients with HC but without AF, and 244 normal controls. LA chamber was assessed for absolute and indexed end-diastolic volume (LAEDV), end-systolic volume, and percent ejection fraction (LAEF). In the 41 prospectively studied patients with HC who developed AF during follow-up, LAEDV was significantly greater than in patients without AF (146 ± 48 vs 107 ± 37 ml) or in normal controls (81 ± 24 ml, p <0.001). Percent LAEF was lower in patients developing AF (36 ± 10%) than without AF (46 ± 12%) or controls (55 ± 9%, p <0.001). Multivariate analysis identified LAEF (<38%), LAEDV (≥118 ml), and age (≥40 years) as independently associated with AF occurrence. In conclusion, CMR measures of LA remodeling and dysfunction reliably identified patients with HC at risk for future development of AF. Decrease in LAEF represents a strong novel marker of susceptibility to AF in this disease. [ABSTRACT FROM AUTHOR]

Whether treatment with β blockers (BBs) is of benefit to patients with hypertrophic cardiomyopathy (HC) and provocable outflow obstruction (with none or with only mild heart failure symptoms) is largely unresolved. Thus, we prospectively studied 27 patients with HC (age 36 ± 15 years; 81% men) with New York Heart Association class I or II, without obstruction at rest, but with exercise-induced left ventricular outflow tract (LVOT) gradient of ≥ 30 mm Hg. Patients underwent exercise echocardiography at baseline and after treatment with nadolol (n = 18; 40 to 80 mg/day) or bisoprolol (n = 9; 5 to 10 mg/day), according to a prespecified protocol. Without the BBs, the postexercise LVOT gradient was 87 ± 29 mm Hg and >50 mm Hg in 25 patients (93%). After a 12 ± 4-month period of BB treatment, the postexercise LVOT gradient had decreased to 36 ± 22 mm Hg (p <0.001) and was virtually abolished (to 0 or <30 mm Hg) in 14 patients (52%), substantially blunted (≥ 20 mm Hg reduction) in 9 (33%), and unchanged in only 4 (15%). Severe postexercise obstruction (range 58 to 80 mm Hg) persisted in 6 patients (22% compared to 93% without BBs; p <0.001). Nonresponders (residual postexercise gradient of ≥ 30 mm Hg with BBs) were characterized by an increased body mass index (hazard ratio 2.03/1 kg/m(2), 95% confidence interval 1.2 to 3.4; p <0.05). In conclusion, in patients with HC with mild or no symptoms, treatment with BBs can prevent the development of LVOT obstruction triggered by physiologic exercise. These findings provide a rationale for the novel strategy of early prophylactic pharmacologic treatment with standard, well-tolerated doses of BBs in physically active patients with provocable gradients, aimed at effective prevention of the hemodynamic burden associated with dynamic obstruction. [ABSTRACT FROM AUTHOR]

Left ventricular (LV) twist represents a phenomenon that links systolic contraction with diastolic relaxation and plays a major role in cardiac physiology; thus, the study of twist mechanics is of particular interest in hypertrophic cardiomyopathy (HC). Three-dimensional speckle tracking echocardiography (3D-STE) has the potential to overcome the limitations of 2-dimensional imaging and provide a greater understanding of LV twist in HC. We aimed to examine LV twist mechanics in HC using 3D-STE. Echocardiograms from subjects with a diagnosis of HC were examined for 3D-STE analysis. Age- and gender-matched healthy subjects were tested as a control group. Forty patients with HC (age 37 ± 16 years; 42.5% women) and 40 control subjects (age 35 ± 10 years; 42.5% women) were examined. Compared with the controls, the patients with HC showed increased peak LV twist (16.5 ± 4.7° vs 12.0 ± 3.9°, p <0.001) mainly because of increased apical rotation of those with LV outflow tract obstruction (obstruction, 12.7 ± 4.4° vs nonobstruction, 9.7 ± 2.8°, p = 0.02). In addition, the patients with HC displayed onset of torsion recoil occurring closer to the aortic valve closure (94 ± 6% vs 85 ± 6%, p <0.001; time normalized by the length of systole), limited completion of untwist during early diastole (31 ± 12% vs 62 ± 15%, p <0.001), and delayed peak untwist velocity (22 ± 7% vs 13 ± 9%, p <0.001; time normalized by the length of diastole). In conclusion, the evaluation of twist mechanics using 3D-STE provides novel insight regarding alterations in LV mechanics in patients with HC. Elucidating the characteristics of the wringing motion of the heart might help to broaden the understanding of the hyperdynamic contraction and impaired relaxation observed in these patients. [Copyright &y& Elsevier]

The relation of exercise-induced left ventricular (LV) outflow tract obstruction to functional capacity in hypertrophic cardiomyopathy (HC) is incompletely defined. Thus, we assessed the patterns of onset of physiologically provoked LV outflow gradients and exercise performance in 74 consecutive patients with HC (age 45 ± 16 years; 74% men) without LV outflow obstruction at rest. The subaortic gradients were measured serially using echocardiography in these 74 patients during maximum, symptom-limited, upright bicycle exercise testing. The time course of the provoked gradients and the relation to exercise performance were assessed. Of the 74 patients, 30 (41%) developed a dynamic LV outflow gradient of ≥30 mm Hg (mean 78 ± 37 mm Hg) during upright exercise testing that correlated highly with the gradients measured with the patients supine during the immediate recovery period (R2 = 0.97). The 16 patients in whom outflow obstruction developed rapidly at low exercise levels (≤5 METs) had a significantly reduced exercise capacity (6.1 ± 1.3 vs 8.0 ± 1.6 METs; p <0.01) compared to the other 14 patients in whom obstruction appeared later at greater exercise levels of >5 METs. The timing of the gradient onset was not predictable from the baseline clinical and echocardiographic features, peak exercise LV outflow tract gradient, or symptoms. In conclusion, in patients with HC without outflow obstruction at rest, the earlier onset of LV outflow tract gradients during physiologic exercise was associated with impaired exercise performance. These findings have provided insights into the determinants of functional impairment in HC and support the potential value of exercise echocardiography in the clinical assessment of patients with HC. [ABSTRACT FROM AUTHOR]

Patients with hypertrophic cardiomyopathy (HC) have coronary microvascular dysfunction, which is an independent predictor of adverse left ventricular remodeling, systolic dysfunction, and mortality in these patients. Whether these defects in vasomotor function are localized to the coronary arteries or whether systemic vasomotor dysfunction is present in patients with HC has not yet been adequately examined. The aim of this study was to test the hypothesis that patients with HC have altered peripheral vascular endothelial function. Subjects without coronary artery disease (CAD) and those with CAD served as negative and positive controls, respectively. Conduit artery endothelium-dependent vasomotion was assessed with ultrasound by measuring flow-mediated dilation of the brachial artery. Flow-mediated dilation was lower in patients with HC compared with those without CAD (p <0.05) but was similar in patients with CAD (p = NS). In conclusion, vasomotor dysfunction in HC is not restricted to the coronary vasculature. Patients with HC have impaired peripheral conduit vessel endothelial function, and the magnitude of impairment is similar to that seen in older patients with advanced CAD. [Copyright &y& Elsevier]

The natural history and clinical course of hypertrophic cardiomyopathy (HC) is diverse, ranging from benign forms compatible with normal or extended longevity to adverse consequences requiring major interventions: surgical myectomy (or selectively alcohol septal ablation) for left ventricular (LV) outflow obstruction producing progressive heart failure; defibrillation and therapeutic hypothermia for cardiac arrest; implantable cardioverter-defibrillators (ICD) for prevention of sudden death; and heart transplant for refractory progressive heart failure in the absence of obstruction.1,2 Patients with HC may have their clinical course importantly influenced by either of these 3 major disease complications,1,2 but the occurrence of all 3 sequentially in a single patient over a 38 year period represents a notable and unusually aggressive form of HC. We present such a patient, prospectively followed and evaluated, who not only has incurred all major adverse consequences of HC but most importantly has survived due to effective treatment modalities available to patients with this disease. [ABSTRACT FROM AUTHOR]

Hypertrophic cardiomyopathy and cardiac amyloidosis result in thickening of the left ventricle, as visualized by 2-dimensional echocardiography. Hemodynamically, hypertrophic cardiomyopathy can be typified by a left ventricular outflow tract gradient and systolic anterior motion of the mitral apparatus, findings rarely seen in cardiac amyloidosis. This case series reports 4 patients with cardiac light-chain amyloidosis and left ventricular outflow tract obstruction at rest, suggesting that there may be echocardiographic overlap between these 2 disparate disease processes. In a series of consecutive patients with cardiac light-chain amyloidosis over a 2-year period, the prevalence of these echocardiographic findings was approximately 4%. In conclusion, awareness of this overlap in echocardiographic presentation may permit more accurate diagnosis, particularly at early stages of amyloid disease, when more treatment options exist. [Copyright &y& Elsevier]

Although tako-tsubo cardiomyopathy (TTC) is regarded as a reversible condition with favorable outcome, a malignant clinical course evolves in some subjects. In this single-institution experience, we describe the clinical profile of patients with adverse TTC outcome. A cohort of 249 consecutive patients with TTC was interrogated for those with acute unstable presentation during the first 24 hours. Forty-seven patients (19%) experienced early complicated clinical course with cardiac arrest in 9 (ventricular fibrillation, n = 4, pulseless electrical activity, n = 3, and asystole, n = 2) or marked hypotension in 38 (systolic blood pressure =90 mm Hg requiring vasopressors and/or balloon pump). Of the 47 patients, Killip class III to IV heart failure was present in 30 (64%). Despite treatment, 8 patients (3%; all women) died inhospital due to respiratory failure, cardiogenic shock, or anoxic brain injury. All 8 inhospital deaths occurred among the 47 patients with unstable presentation, including 2 after cardiac arrest and 6 with marked hypotension. Post-TTC event mortality for a period of 4.7 ± 3.4 years significantly exceeded that in a matched general US population (standardized mortality ratio 1.4; 95% confidence interval 1.1 to 1.9; p = 0.005) largely due to noncardiac co-morbidities. In conclusion, contrary to widespread perception, TTC is not an entirely benign and reversible condition. Among this large cohort, a high-risk subgroup was identified with cardiac arrest or hemodynamic instability, accounting for all hospital deaths. Hospital nonsurvivors had a variety of irreversible co-morbid conditions with the potential to compromise clinical status and adversely affect short-term survival. Long-term survival after hospital discharge was also reduced compared with the general population because of noncardiac co-morbidities [ABSTRACT FROM AUTHOR]

Risk stratification for sudden death (SD) is an essential component of hypertrophic cardiomyopathy (HC) management, given the proven effectiveness of implantable cardioverter-defibrillators (ICD) for preventing SD. Although highly effective in identifying high-risk patients, current stratification algorithms remain incomplete and novel strategies are encouraged. In this regard, reliability of the statistical model to predict SD risk in HC, as recommended by the recent European Society of Cardiology (ESC) guidelines, was retrospectively tested in an independent cohort of 1,629 consecutive patients with HC aged =16 years. Of the 1,629 patients, 35 incurred SD events, but only 4 of these (11%) had high predictive risk scores >6%/5 years consistent with an ICD recommendation, and most (60%; n = 21) had scores <4%/5 years that would not justify ICDs. Of 46 high-risk patients with appropriate ICD interventions for ventricular fibrillation/tachycardia, 27 (59%) had low SD risk scores of <4%/5 years, regarded by ESC as insufficient to recommend ICDs, and only 12 (26%) had scores >6%/5 years, considered an ICD indication; 11 of these 12 had already met conventional criteria warranting implantation with 2 to 3 risk markers. Of 414 patients with ICDs but without appropriate interventions, 258 (62%) had low risk scores (<4%/5 years) that would argue against implant. In conclusion, primary risk stratification using the ESC prognostic score applied retrospectively to a large independent HC cohort proved unreliable for prediction of future SD events. Most patients with HC with SD or appropriate ICD interventions were misclassified with low risk scores and therefore would have remained unprotected from arrhythmic SD without ICDs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article reflects on the treatment strategies for symptomatic patients with obstructive hypertrophic cardiomyopathy (HC) and focuses on the need of more myectomy surgeons and disease-specific centers. It discusses the issues regarding the expansion of the myectomy operation which has been arisen due to the shortage of surgeons. It suggests promotion and growth of HC centers and mentions the Tufts Medical Center in Boston, Massachusetts.

Preparticipation screening of athletes with 12-lead electrocardiography has been promoted for the detection of asymptomatic cardiovascular disease, particularly hypertrophic cardiomyopathy (HC). Although false-positive electrocardiographic (ECG) results for HC are well recognized in athlete screening, expected false-negative rates are unknown. The aim of this study was to characterize the rate of false-negative ECG findings in a cohort of young asymptomatic patients with phenotypically expressed HC, defined by cardiovascular magnetic resonance, using the 2010 European Society of Cardiology recommended ECG criteria for the identification of suspected heart disease in trained athletes. Cardiac magnetic resonance studies and 12-lead electrocardiography were performed in 114 consecutive asymptomatic patients with HC aged ≤35 years (mean age 22 ± 8 years; 77% male patients). Electrocardiograms were analyzed to distinguish pathologic ECG patterns from alterations considered nonpathologic and physiologic consequences of athletic training. Among the 114 patients with HC, 103 (90%) demonstrated ≥1 pathologic ECG abnormality, while the remaining 11 patients (10%) had normal or nonpathologic ECG patterns and therefore defined a subgroup in whom ECG screening would not be expected to raise suspicion of heart disease (i.e., false-negative results). In this false-negative ECG results group, maximal left ventricular wall thickness was 17 ± 2 mm (range 15 to 21), compared to patients with pathologic ECG patterns, in whom maximal left ventricular wall thickness was 22 ± 5 mm (p = 0.003). In conclusion, a substantial minority of young asymptomatic patients with HC with phenotypically expressed left ventricular hypertrophy have nonpathologic ECG findings on the basis of the 2010 European Society of Cardiology guidelines. In principle, this high false-negative rate of 10% represents an important limitation in applying 12-lead electrocardiography to large, apparently healthy athletic populations for the detection of HC. [Copyright &y& Elsevier]

In hypertrophic cardiomyopathy (HCM), the clinical significance attributable to the broad range of left ventricular (LV) systolic function, assessed as the ejection fraction (EF), is incompletely resolved. We evaluated the EF using cardiovascular magnetic resonance (CMR) imaging in a large cohort of patients with HCM with respect to the clinical status and evidence of left ventricular remodeling with late gadolinium enhancement (LGE). CMR imaging was performed in 310 consecutive patients, aged 42 ± 17 years. The EF in patients with HCM was 71 ± 10% (range 28% to 89%), exceeding that of 606 healthy controls without cardiovascular disease (66 ± 5%, p <0.001). LGE reflecting LV remodeling showed an independent, inverse relation to the EF (B-0.69, 95% confidence interval −0.86 to −0.52; p <0.001) and was greatest in patients with an EF <50%, in whom it constituted a median value of 29% of the LV volume (interquartile range 16% to 40%). However, the substantial subgroup with low-normal EF values of 50% to 65% (n = 45; 15% of the whole cohort), who were mostly asymptomatic or mildly symptomatic (37 or 82% with New York Heart Association functional class I to II), showed substantial LGE (median 5% of LV volume, interquartile range 2% to 10%). This overlapped with the subgroup with systolic dysfunction and significantly exceeded that of patients with an EF of 66% to 75% and >75% (median 2% of the LV volume, interquartile range 1.5% to 4%; p <0.01). In conclusion, in a large cohort of patients with HCM, a subset of patients with low-normal EF values (50% to 65%) was identified by contrast-enhanced CMR imaging as having substantial degrees of LGE, suggesting a transition phase, potentially heralding advanced LV remodeling and systolic dysfunction, with implications for clinical surveillance and management. [Copyright &y& Elsevier]

Stress (takotsubo) cardiomyopathy (SC) is a recently recognized syndrome with clinical and electrocardiographic (ECG) presentation resembling ST elevation anterior myocardial infarction. As experience with this condition has evolved, a more diverse spectrum of 12-lead ECG patterns has emerged that may affect differential diagnosis. Fifty-nine consecutive patients with SC were prospectively identified at a large community-based cardiology practice. All were women aged 32 to 90 years (mean 66 ± 13) with acute chest pain triggered by emotional or physical incidents and with akinesia of the mid-distal left ventricle; each patient recovered and was discharged within a median of 4 days. On electrocardiography, anterior ST elevation was most common (33 [56%]), with magnitudes less than in controls with left anterior descending coronary artery occlusions (1.4 ± 1.5 vs 2.4 ± 2.2 mm, p <0.001), with considerable overlap. ECG findings in 26 other patients (44%) without ST elevation revealed diffuse T-wave inversion (10 [17%]) and healed anterior infarctions (6 [10%]) or were nonspecific (5 [8.5%]) or normal (5 [8.5%]). Troponin elevations occurred in 56 patients with SC (95%). The mean peak troponin T level was significantly lower in patients with SC (0.64 ± 0.86 ng/ml) than in those with left anterior descending coronary artery occlusions (3.88 ± 4.9 ng/ml) (p <0.0001). Patients with SC with or without ST elevation did not differ with respect to the ejection fraction (29 ± 9% vs 34 ± 9%, respectively, p = NS) or Thrombolysis In Myocardial Infarction (TIMI) frame counts. During recovery, diffuse T-wave inversion evolved in 49 patients with SC (83%). In conclusion, patients with SC present with diverse ECG findings, and no single pattern alone can reliably distinguish this condition from acute coronary syndromes. The diagnosis of SC requires heightened awareness of its unique clinical profile as well as coronary arteriography and left ventriculography. [Copyright &y& Elsevier]

Increased thickness of the left ventricular (LV) wall is the predominant feature of the hypertrophic cardiomyopathy (HC) phenotype. The structural characteristics of the LV papillary muscles (PMs) have received little attention. In this study, cardiovascular magnetic resonance (CMR) was used to characterize PM morphology in a large HC population. Cine and delayed enhancement (DE) CMR images were obtained in 201 patients with HC and 43 control subjects. PM number and mass index were greater in patients with HC compared with controls (2.5 vs 2.1, p <0.001, and 6 ± 2 vs 3 ± 2 g/m2, p <0.001, respectively), including 109 (54%) with PM mass ≥7 g/m2 (≥2 SDs above the mean for controls). Greater LV wall mass index was associated with more substantial PM mass (r = 0.09, p <0.001). Furthermore, 12 patients with HC (19%) had normal LV mass with localized wall thickness but increased PM mass. In patients with HC with LV outflow obstruction at rest, PMs were positioned closer to the ventricular septum (displaced anteriorly: 58% vs 42% for subjects without obstruction, p = 0.02), with more marked hypertrophy (9 ± 5 vs 6 ± 4 g/m2, p <0.001). Preoperative CMR identified 3 patients with accessory, anteriorly displaced PMs judged to contribute to outflow obstruction, which were resected during septal myectomy. DE of the PMs was identified in 13 patients with HC (6%), including 3 with DE confined to PMs. In conclusion, CMR demonstrates LV PMs to be part of the cardiomyopathic process in HC, with increases in number and mass, and not uncommonly associated with remodeling with DE. The identification of accessory PMs may be useful in planning preoperative strategy. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

In a consecutive, prospectively assessed and unselected hypertrophic cardiomyopathy (HC) cohort closely resembling the true disease state, QTc dispersion (and QTc) on the 12-lead electrocardiogram did not prove to be a reliable predictor of HC-related sudden death. Therefore, QT dispersion would not appear to be useful in devising future risk stratification strategies for predicting sudden death in HC. [ABSTRACT FROM AUTHOR]

Hypertrophic cardiomyopathy (HC) has become a contemporary and treatable genetic heart disease, now with disease-related mortality reduced to as low as 0.5% per year, based largely on more effective risk stratification and the use of the implantable cardioverter-defibrillator for primary prevention of sudden death. This paradigm change in the natural history of HC has caused us to reconsider the overall mortality risk in this disease. We interrogated the databases of 2 HC referral centers, Minneapolis Heart Institute and Tufts Medical Center. Of 1,902 consecutive patients evaluated between 1992 and 2013, 1,653 patients (87%) have survived to the end of follow-up and 249 patients (13%) have died. Most deaths (178 of 249; 72%) were unrelated to HC, commonly because of cancer and predominantly in older patients. Non-HC mortality was significantly more common in adults presenting ≥ 60 years and least common in the youngest patients aged <30 years (p <0.001). Notably, deaths from non-HC causes substantially exceeded HC-related causes by 2.6-fold (p <0.001). In conclusion, only about 25% of patients with HC ultimately died of their disease, including predominantly those who were <30 years of age. These data allow patients with HC to develop a more realistic and reassured perception of their disease. [ABSTRACT FROM AUTHOR]

We found a highly inconsistent relation between the granular and reflective ultrasound ("speckling") pattern frequently observed in the ventricular septum of patients with hypertrophic cardiomyopathy and evidence of myocardial fibrosis by contrast-enhanced cardiovascular magnetic resonance imaging. Therefore, this distinctive echocardiographic appearance of the myocardium does not accurately characterize left ventricular scarring and is most likely explained as an extraneous ultrasound signal pattern. In conclusion, myocardial fibrosis in patients with hypertrophic cardiomyopathy is most reliably identified using contrast-enhanced cardiovascular magnetic resonance imaging. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Significance of false negative electrocardiograms in preparticipation screening of athletes for hypertrophic cardiomyopathy." by E. J. Rowin et al. in the August 2012 issue and a response from the author is also presented.

Hypertrophic cardiomyopathy (HCM) is a relatively common often inherited heart disease encumbered throughout much of its almost 60-year history by the expectation of an unfavorable outcome with shortened longevity. However, it is notable that in 2023, most patients affected with HCM can now achieve normal or extended life expectancy without major disability because of a comprehensive constellation of management strategies that have evolved largely over the last 20 years. Distinct adverse disease pathways dictate high-benefit low-risk personalized treatments, without reliance on genomics and sarcomere mutations, including: primary prevention implantable defibrillators for sudden cardiac death prevention, surgical myectomy and percutaneous alcohol septal ablation to reverse heart failure symptoms, anticoagulation to prevent embolic stroke associated with concomitant atrial fibrillation, external defibrillation and hypothermia for out-of-hospital cardiac arrest, and heart transplant in a small patient subgroup with end-stage disease. Large cohort studies using these contemporary management strategies achieved remarkably low HCM-related mortality (0.5%/year) across all age groups, which is lower than in the other cardiac or noncardiac risks of living, and largely confined to nonobstructive patients with progressive heart failure, including those awaiting heart transplant., Competing Interests: Declaration of competing interest Dr. Martin Maron declares steering committee member SEQUIOA-HCM. Consultant Imbria and Edgewise. The remaining authors have no competing interest to declare., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Hypertrophic cardiomyopathy (HCM) is a relatively common and, often, inherited cardiac disease, once regarded as largely untreatable with ominous prognosis and, perhaps, most visibly as a common cause of sudden cardiac death (SCD) in the young. However, HCM is now more accurately considered a treatable disease with management options that significantly alter its clinical course. This is particularly true for SCD because the penetration of implantable cardioverter-defibrillators into HCM practice enables primary prevention device therapy that reliably terminates potentially lethal ventricular tachyarrhythmias (3% to 4%/year). This therapeutic advance is largely responsible for >10-fold decrease in the overall disease-related mortality to 0.5%/year, independent of patient age. A guideline-based clinical risk stratification algorithm has evolved, which included variables identifiable with cardiac magnetic resonance: ≥1 risk markers judged major within the clinical profile of an individual patient, associated with a measure of physician judgment and shared decision-making, can be sufficient to consider the recommendation of a prophylactic defibrillator implant. Implantable cardioverter-defibrillator decisions using the American College of Cardiology and the American Heart Association traditional major risk marker strategy are associated with a 95% sensitivity for identifying those patients who subsequently experience appropriate therapy, albeit often 5 to 10+ years after implant but without heart failure deterioration or death after a device intervention. A mathematical SCD risk score proposed by European Society of Cardiology is associated with a relatively low sensitivity (33%) for predicting and preventing SCD events but with potential for less device overtreatment., Competing Interests: Declaration of competing interest Dr. Martin Maron declares Steering Committee Member, SEQUIOA-HCM; Consultant: Imbria and Edgewise. The remaining authors have no competing interest to declare., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Surgical myectomy remains the time-honored primary treatment for hypertrophic cardiomyopathy patients with drug refractory limiting symptoms due to LV outflow obstruction. Based on &gt;50 years experience, surgery reliably reverses disabling heart failure by permanently abolishing mechanical outflow impedance and mitral regurgitation, with normalization of LV pressures and preserved systolic function. A consortium of 10 international currently active myectomy centers report about 11,000 operations, increasing significantly in number over the most recent 15 years. Performed in experienced multidisciplinary institutions, perioperative mortality for myectomy has declined to 0.6%, becoming one of the safest currently performed open-heart procedures. Extended myectomy relieves symptoms in &gt;90% of patients by ≥ 1 NYHA functional class, returning most to normal daily activity, and also with a long-term survival benefit; concomitant Cox-Maze procedure can reduce the number of atrial fibrillation episodes. Surgery, preferably performed in high volume clinical environments, continues to flourish as a guideline-based and preferred high benefit: low treatment risk option for adults and children with drug refractory disabling symptoms from obstruction, despite prior challenges: higher operative mortality/skepticism in 1960s/1970s; dual-chamber pacing in 1990s, alcohol ablation in 2000s, and now introduction of novel negative inotropic drugs potentially useful for symptom management., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Atrial fibrillation (AF) is the most common sustained arrhythmia in hypertrophic cardiomyopathy (HCM) and is an important cause of morbidity and embolic stroke. The impact of outflow obstruction and the influence of surgical septal myectomy on the development of new-onset AF has not been well described. Consecutive patients with HCM without previous AF were followed for 5.0 ± 3.6 years for new-onset AF, including 717 with obstruction who did not undergo surgical myectomy (outflow gradients ≥30 mm Hg at rest or after provocation), 555 with nonobstructive HCM (outflow gradients &lt;30 mm Hg), and 503 who underwent surgical myectomy. Patients with obstructive HCM who did not undergo myectomy had a 1.5-fold increased risk for new-onset AF compared with nonobstructive HCM (26% vs 16% at 10 years, hazard ratio = 0.69, p = 0.02). Patients who underwent myectomy had more advanced heart failure (95% vs 18% New York Heart Association class III, p &lt;0.001) and had larger left atrium dimension (42 ± 7 vs 41 ± 7 mm; p &lt;0.01) as compared with patients with obstructive HCM who did not undergo myectomy. However, after myectomy, the risk of new-onset AF was significantly lower than nonoperated obstructive (17% vs 26% at 10 years, p = 0.04) and no different from the risk of AF in patients with nonobstructive HC (hazard ratio 0.95, p = 0.81). In conclusion, patients with HCM with outflow obstruction are at a higher risk for AF compared with patients with nonobstructive HCM. However, after surgical myectomy, the risk for new-onset AF is substantially reduced. In addition to the known benefits of myectomy to permanently relieve outflow tract obstruction and mitral regurgitation, reverse heart failure symptoms, and increase longevity, myectomy is now shown to decrease susceptibility to AF in HCM., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Hypertrophic cardiomyopathy (HCM) is a global and relatively common cause of patient morbidity and mortality and is among the first reported monogenic cardiac diseases. For 30 years, the basic etiology of HCM has been attributed largely to variants in individual genes encoding cardiac sarcomere proteins, with the implication that HCM is fundamentally a genetic disease. However, data from clinical and network medicine analyses, as well as contemporary genetic studies show that single gene variants do not fully explain the broad and diverse HCM clinical spectrum. These transformative advances place a new focus on possible novel interactions between acquired disease determinants and genetic context to produce complex HCM phenotypes, also offering a measure of caution against overemphasizing monogenics as the principal cause of this disease. These new perspectives in which HCM is not a uniformly genetic disease but likely explained by multifactorial etiology will also unavoidably impact how HCM is viewed by patients and families in the clinical practicing community going forward, including relevance to genetic counseling and access to healthcare insurance and psychosocial wellness., (Published by Elsevier Inc.)

The clinical profile of patients with obstructive hypertrophic cardiomyopathy (oHC) is not well characterized, with little evidence outside selected referral populations. Using longitudinal medical claims data from a United States nationwide database, we retrospectively identified adults who were newly diagnosed with oHC. Clinical characteristics were compared from 1 year before diagnosis and at the 2-year follow-up. Patients (N = 1,841) with oHC (age 63 ± 15 years; 52% were male) with geographic representation across the United States were identified. Most patients received care within community-based cardiovascular practices and 7% at referral hypertrophic cardiomyopathy (HC) centers. Baseline diagnostic procedures included electrocardiogram (66%), echocardiogram (51%), magnetic resonance imaging (4%), and HC genetic testing (0.7%). Baseline co-morbidities were hypertension (59%), coronary artery disease (30%), diabetes (19%), and atrial fibrillation (19%). For all HC-related medications, use significantly increased after diagnosis. During follow-up, 144 patients (8%) received an implantable cardioverter-defibrillator for sudden death prevention, 99 underwent septal myectomy (5%), and 24 underwent alcohol septal ablation (1%). By the 1-year follow-up, 2% of patients had sudden cardiac arrest and 26% had atrial fibrillation, and heart failure increased from 16% to 27%. In conclusion, in a community-based population of patients with oHC, patients' age at diagnosis of oHC was older than reported for referral populations and patients had a significant co-morbidity burden. Cardiovascular medication use was appropriate, but the rate of guideline-supported surgical procedures was low., Competing Interests: Disclosures Dr. Rowin has no relevant disclosures to report. Dr. Maron is a steering committee member at Cytokinetics, Inc. Teng, Tan, and Dr. Stanek are employees of HealthCore. Michael Butzner is an employee of Cytokinetics, Inc. Sarocco and Dr. Robertson were employees of Cytokinetics, Inc., at the time the research was conducted. Dr. Rowin has no conflicts of interest to declare. Data statement. Research data are confidential and will not be available., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

For over 50 years, surgical septal myectomy has been the preferred treatment for drug-refractory heart failure symptoms in obstructive hypertrophic cardiomyopathy (HCM). However, given the relatively youthful adult ages at which HCM surgery is usually performed, it is informative to evaluate longer-term results of myectomy after ≥10 years. We identified 139 consecutive obstructive HCM patients (50 ± 15 years of age; 55% men) who underwent surgical myectomy, 2003 to 2010 at Tufts HCM Center and followed 11.3 ± 2.7 years (range to 17). Operative mortality was low (0.6%) and left ventricular (LV) outflow gradients at rest were reduced from 56 ± 40 mm Hg preoperatively to 1 ± 7 mm Hg postoperatively, durable over the study period, with no patient requiring reoperation for the residual gradient. Over follow-up, 129 of 139 patients (93%) were alive ≥10 years after myectomy, including 17 patients ≥15 years. Of 118 patients with complete long-term clinical follow-up data, 109 (92%) experienced clinical improvement to New York Heart Association classes I or II. In 9 patients (8%) refractory class III/IV symptoms reoccurred 6.6 ± 3.9 years postoperatively, including 4 who ultimately underwent a heart transplant. After myectomy, there were 2 late HCM-related deaths, but none suddenly; notably 6 patients (12%) with prophylactic implantable cardioverter-defibrillators experienced appropriate therapy terminating ventricular tachycardia/ventricular fibrillation after myectomy. Survival following myectomy was 91% at 10 years (95% confidence interval: 85, 96%) not different from the age- and gender-matched general United States population (log-rank p = 0.64). In conclusion, myectomy provides permanent abolition of outflow gradients with reversal of heart failure and highly favorable long-term survival, representing a low-risk:high-benefit option when performed in experienced HCM centers. Myectomy did not protect absolutely against arrhythmic sudden death events, underscoring the importance of risk stratification in operative patients., Competing Interests: Disclosures Dr. M.S. Maron reports a relationship with Cytokinetics Inc. that includes: consulting or advisory; and is a consultant for Imbria Pharmaceuticals and Takeda pharmaceuticals. The other authors have no conflicts of interest to declare., (Copyright © 2021. Published by Elsevier Inc.)

While predicting prognosis to anticipate adverse disease course has long been an aspiration in hypertrophic cardiomyopathy (HC), reliable markers of progressive and unrelenting heart failure symptoms in the absence of obstruction are not well characterized. We sought to evaluate markers of systolic function, including the role of global longitudinal strain (GLS), to identify nonobstructive HC patients at risk for future heart failure. A cohort of 296 consecutive nonobstructive HC patients (42 ± 18years; 75% male) with NYHA class I/II symptoms and preserved systolic function at study entry (EF: 65 ± 6%), were followed for progressive heart failure symptoms (increase in ≥ 1 NYHA functional class) and/or development of systolic dysfunction (EF < 50%). Over median follow-up of 4 ± 3 years, 35 study patients (10%) experienced new heart failure events, including 31 with progressive symptoms and 4 who developed systolic dysfunction. Abnormal GLS < 16% was associated with a 5-fold increase in risk for heart failure compared to GLS > 18% (p < 0.001). GLS remained an independent predictor of heart failure even after adjustment for other relevant disease variables including EF (OR 1.23, p = 0.005). However, notably, when GLS and EF were combined, the prediction of heart failure for individual patients was enhanced (net reclassification improvement 0.55; p = 0.002). Together, GLS < 16% and EF 50% to 59% were associated with a 12.5-fold greater risk for heart failure versus patients with GLS > 18% and EF ≥ 60%, who were at the lowest risk. In conclusion, in nonobstructive HC with no or mild symptoms and preserved EF, abnormal GLS is a strong independent predictor for subsequent development of progressive heart failure symptoms and/or systolic dysfunction. Furthermore, the greatest power in predicting outcome in nonobstructive HC is achieved by combining GLS with EF to identify HC patients at the highest risk for heart failure progression and systolic dysfunction., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Major advances in diagnosis and treatment have emerged for hypertrophic cardiomyopathy (HCM), largely in major tertiary referral centers dedicated to this disease. Whether these therapeutic benefits are confined to patients in such highly selected cohorts, or can be implemented effectively in independent regional or community-based populations is not generally appreciated. We assessed management and clinical outcomes in a non-referral HCM center (n = 214 patients) in Eastern Pennsylvania. Over a 6.0 ± 3.2-year follow-up, the HCM-related mortality rate was 0.1% per year attributed to a single disease-related death, in a 49-year-old man with end-stage heart failure, ineligible for heart transplant. Fifteen patients (7%) with prophylactically placed implantable cardioverter-defibrillators (ICDs) experienced appropriate therapy terminating life-threatening ventricular tachyarrhythmias. In 23 other patients (11%; 5%/year), heart failure due to left ventricular outflow obstruction was reversed by surgical septal myectomy (n = 20) or percutaneous alcohol septal ablation (n = 3). This regional HCM cohort was similar to a comparison tertiary center referral population in terms of HCM-mortality: 0.1%/year vs 0.3%/year (p = 0.3) and ICD therapy (31% vs 16% of primary prevention implants), although more frequently with uncomplicated benign clinical course (62% vs 46%; p <0.01). In conclusion, effective contemporary HCM management strategies and outcomes in referral-based HCM centers can be successfully replicated in regional and/or non-referral settings. Therefore, HCM is now a highly treatable disease compatible with normal longevity when assessed in a variety of clinical venues not limited to tertiary centers., (Copyright © 2020. Published by Elsevier Inc.)