In patients with hypertrophic cardiomyopathy, left ventricular outflow tract obstruction at rest is a strong, independent predictor of progression to severe symptoms of heart failure and of death.

Background-A clinical entity characterized by acute but rapidly reversible left ventricular (LV) systolic dysfunction and triggered by psychological stress is emerging, with reports largely confined to Japan. Methods and Results-Over a 32-month period, 22 consecutive patients with this novel cardiomyopathy were prospectively identified within a community-based practice in the Minneapolis-St. Paul, Minn, area. All patients were women aged 32 to 89 years old (mean 65Ϯ13 years); 21 (96%) were Ն50 years of age. The syndrome is characterized by (1) acute substernal chest pain with ST-segment elevation and/or T-wave inversion; (2) absence of significant coronary arterial narrowing by angiography; (3) systolic dysfunction (ejection fraction 29Ϯ9%), with abnormal wall motion of the mid and distal LV, ie, "apical ballooning"; and (4) profound psychological stress (eg, death of relatives, domestic abuse, arguments, catastrophic medical diagnoses, devastating financial or gambling losses) immediately preceding and triggering the cardiac events. A significant proportion of patients (37%) had hemodynamic compromise and required vasopressor agents and intra-aortic balloon counterpulsation. Each patient survived with normalized ejection fraction (63Ϯ6%; PϽ0.001) and rapid restoration to previous functional cardiovascular status within 6Ϯ3 days. In 95%, MRI identified diffusely distributed segmental wall-motion abnormalities that encompassed LV myocardium in multiple coronary arterial vascular territories. Conclusions-A reversible cardiomyopathy triggered by psychologically stressful events occurs in older women and may mimic evolving acute myocardial infarction or coronary syndrome. This condition is characterized by a distinctive form of systolic dysfunction that predominantly affects the distal LV chamber and a favorable outcome with appropriate medical therapy.

Hypertrophic cardiomyopathy is a common inherited cardiovascular disease present in one in 500 of the general population. It is caused by more than 1400 mutations in 11 or more genes encoding proteins of the cardiac sarcomere. Although hypertrophic cardiomyopathy is the most frequent cause of sudden death in young people (including trained athletes), and can lead to functional disability from heart failure and stroke, the majority of affected individuals probably remain undiagnosed and many do not experience greatly reduced life expectancy or substantial symptoms. Clinical diagnosis is based on otherwise unexplained left-ventricular hypertrophy identified by echocardiography or cardiovascular MRI. While presenting with a heterogeneous clinical profile and complex pathophysiology, effective treatment strategies are available, including implantable defibrillators to prevent sudden death, drugs and surgical myectomy (or, alternatively, alcohol septal ablation) for relief of outflow obstruction and symptoms of heart failure, and pharmacological strategies (and possibly radiofrequency ablation) to control atrial fibrillation and prevent embolic stroke. A subgroup of patients with genetic mutations but without left-ventricular hypertrophy has emerged, with unresolved natural history. Now, after more than 50 years, hypertrophic cardiomyopathy has been transformed from a rare and largely untreatable disorder to a common genetic disease with management strategies that permit realistic aspirations for restored quality of life and advanced longevity.

In this large SC cohort, the clinical spectrum was heterogeneous with about one-third either male,

Background-Nonobstructive hypertrophic cardiomyopathy (HCM) has been regarded as the predominant hemodynamic form of the disease on the basis of assessment of outflow gradient under resting conditions. We sought to prospectively define the prevalence, clinical profile, and significance of left ventricular (LV) outflow tract obstruction under resting conditions and with physiological exercise in a large HCM cohort. Methods and Results-We prospectively analyzed 320 consecutive HCM patients (age, 47Ϯ17 years), measuring LV outflow gradient at rest, with Valsalva maneuver, and with exercise echocardiography. LV outflow obstruction was present at rest and/or with exercise in 225 patients (70%); 119 had rest gradients Ն50 mm Hg and were not exercised.Of the other 201 patients with gradients Ͻ50 mm Hg at rest (average, 4Ϯ9 mm Hg), 106 developed mechanical obstruction to LV outflow resulting from mitral valve-septal contact after exercise (80Ϯ43 mm Hg), including 76 with marked gradients Ն50 mm Hg and 46 with heart failure symptoms. The remaining 95 patients (30%) had no or small gradients (Ͻ30 mm Hg) both at rest and with exercise. Valsalva maneuver underestimated the presence and magnitude of exercise-induced obstruction. Conclusions-Among those patients who come to clinical evaluation, HCM is a predominantly obstructive disease in which LV outflow gradients, frequently associated with heart failure symptoms and often identified only with exercise, are evident in most patients (ie, 70%

M ore than 50 years after its contemporary description, hypertrophic cardiomyopathy (HCM) remains the most common cause of sudden death in the young. [1][2][3][4][5][6] Although several clinical markers have proved to be useful guides for risk stratification, 3-5,7 current strategies do not identify all HCM patients at risk for sudden death. 3,5,8,9 Over the last Background-Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden death in the young, although not all patients eligible for sudden death prevention with an implantable cardioverter-defibrillator are identified. Contrast-enhanced cardiovascular magnetic resonance with late gadolinium enhancement (LGE) has emerged as an in vivo marker of myocardial fibrosis, although its role in stratifying sudden death risk in subgroups of HCM patients remains incompletely understood. Methods and Results-We assessed the relation between LGE and cardiovascular outcomes in 1293 HCM patients referred for cardiovascular magnetic resonance and followed up for a median of 3.3 years. Sudden cardiac death (SCD) events (including appropriate defibrillator interventions) occurred in 37 patients (3%

Hypertrophic cardiomyopathy (HCM) is an important genetic heart muscle disease for which prevalence in the general population has not been completely resolved. For the past 20 years, most data have supported the occurrence of HCM at about 1 in 500. However, the authors have interrogated a number of relevant advances in cardiovascular medicine, including widespread fee-for-service genetic testing, population genetic studies, and contemporary diagnostic imaging, as well as a greater index of suspicion and recognition for both the clinically expressed disease and the gene-positive-phenotype-negative subset (at risk for developing the disease). Accounting for the potential impact of these initiatives on disease occurrence, the authors have revisited the prevalence of HCM in the general population. They suggest that HCM is more common than previously estimated, which may enhance its recognition in the practicing cardiovascular community, allowing more timely diagnosis and the implementation of appropriate treatment options for many patients.

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