Faculty Bibliography

A 70-year-old male with known hypertrophic cardiomyopathy (HCM) and latent obstruction presented with new onset of cardiogenic shock. He had a new resting left ventricular (LV) outflow gradient of 90 mmHg, and new severe LV systolic dysfunction. Because of rapid deterioration despite medical management he was urgently sent for surgical relief of obstruction, which immediately reversed both the LV dysfunction and shock. A second patient, a 58-year-old male also with hypertrophic cardiomyopathy and latent obstruction presented with collapse, cardiogenic shock, 135 mmHg resting LV outflow gradient and new severe LV systolic dysfunction. His profound shock was irreversible with pharmacologic management, but surgical relief of obstruction reversed both his LV dysfunction and shock. Echocardiography plays a pivotal role in the management of these acutely ill patients.

BACKGROUND: The ideal provocative maneuver in patients with hypertrophic cardiomyopathy (HCM) is a subject of ongoing investigation. Standing is a fundamental activity of daily life. This study examined acquisition of standing, Valsalva, and post-exercise left ventricular outflow tract gradients in HCM. METHODS: Rest supine, standing, and post-Valsalva gradients were measured in 98 consecutive patients with HCM who were referred for outpatient echocardiography. In 53 (54%) of the 98 patients, symptom-limited treadmill exercise was also performed, with gradients measured immediately after in the supine position. RESULTS: Fifty-six (57%) of the 98 patients had resting gradient<30 mm Hg and would thus be characterized as nonobstructive at rest. In the 98 patients, median gradients were 25 mm Hg at rest (range 0-205 mm Hg), increasing to 44 mm Hg after standing (range 0-309 mm Hg), an increase of 76%, and were again higher after Valsalva, 64 mm Hg (range 0-256 mm Hg) (P<.001). In the 53 patients who had gradient assessed after exercise, they were higher still, 100 mm Hg (range 0-256 mm Hg) (P<.001). In 29 patients (30%), standing provoked a higher gradient than Valsalva. CONCLUSION: Although standing increased gradients by 76%, it is not as potent a provocative maneuver as Valsalva or treadmill exercise. Nevertheless, standing is recommended as a physiologic provocative maneuver. In some patients standing may guide therapy; in others, the standing and exercise gradient provide a correct appreciation of the range of physiologically experienced gradients during daily upright activity.

Few other diseases show the degree of phenotypic heterogeneity expressed by HC. The two novel patients reported here with isolated posterobasal LV free wall hypertrophy (and mitral valve prolapse) extend this morphologic diversity even farther, now 3 decades after the introduction of contemporary 2-dimensional imaging.

This study examines acute effect of dual-chamber (DDD) pacing combined with disopyramide for left ventricular outflow tract (LVOT) gradient reduction in obstructive hypertrophic cardiomyopathy (HCM) patients. Among 24 patients refractory to maximal drug therapy, 7 had a significant improvement of LVOT gradient by DDD pacing alone. In the remaining 17 patients, the LVOT gradient reduction was 26+/-19% after DDD pacing alone and 35+/-16% after intravenous disopyramide alone. In contrast, after the combined therapy of DDD pacing and disopyramide, pressure gradient decreased from 102+/-35 to 28+/-23 mm Hg, a reduction of 72+/-21%. We have demonstrated synergy between DDD pacing and disopyramide for LVOT gradient reduction in obstructive HCM. Study of the long-term effects of this combined therapy would be the next step to ascertain clinical utility.

Electrocardiographic (ECG) abnormalities are common in hypertrophic cardiomyopathy (HC) and have been associated with the distribution of left ventricular hypertrophy and myocardial fibrosis. Such abnormalities may predispose patients to electrophysiologic instability, ventricular arrhythmias, and sudden cardiac death (SCD). We studied 330 patients with HC who were judged clinically to be at high risk for SCD and therefore received automatic implantable cardioverter-defibrillators (ICDs). Surface 12-lead electrocardiograms acquired at the time of ICD implantation were analyzed and the ECG characteristics of patients with appropriate device interventions for ventricular tachycardia and fibrillation were compared to those patients without appropriate device interventions. The 330 patients were followed for 3.7 +/- 3.0 years after implantation and 57 patients (17%) had appropriate discharges. No differences in the ECG characteristics of patients with and without appropriate device interventions were identified. Markedly increased ECG voltages, QRS duration, left or rightward QRS axis, abnormal Q waves, and QTc or QT dispersion were not associated with appropriate ICD discharge. Conversely, normal electrocardiograms and electrocardiograms normal except for a repolarization abnormality in only 1 anatomic distribution were not associated with freedom from ICD discharge. Moreover, no combination of ECG variables was associated with the likelihood of an appropriate ICD discharge. In conclusion, in a cohort of patients with HC selected because of their high risk for SCD, 12-lead surface electrocardiogram did not predict subsequent appropriate ICD intervention for ventricular tachyarrhythmias and was not useful in risk stratification for sudden death.

The implantable cardioverter-defibrillator (ICD) therapy is an established intervention for the prevention of sudden cardiac death (SCD) in patients with significant left ventricular dysfunction. Multiple randomized clinical trials have studied the use of ICD for the primary and secondary SCD. These studies were performed in patients with left ventricular dysfunction from coronary artery disease or dilated cardiomyopathy, and the marker of reduced ejection fraction has emerged for selecting patients who would benefit from ICD therapy. Currently, for most of these patients the decision to implant, or not, is determined by relatively straightforward paradigms. The same cannot be said for the genetic cardiac diseases associated with SCD--long QT syndrome, Brugada syndrome, hypertrophic cardiomyopathy, and arrhythmogenic right ventricular dysplasia. Indications for ICD in these conditions are very much a work-in-progress.

Arrhythmogenic right ventricular dysplasia (ARVD), also known as arrhythmogenic right ventricular cardiomyopathy, is a genetic cause for sudden cardiac arrest. In ARVD, there is progressive replacement of normal myocytes, with fat and fibrous tissue, predominantly in the right ventricle that predisposes the individual to arrhythmias. Patients who are identified with this condition are risk stratified; those at high risk are recommended to have implanted cardioverter defibrillators.

Sudden cardiac death (SCD) in young athletes is generally caused by inherited cardiac disorders. While these events are relatively few compared to other cardiac deaths, they are tragic in that death occurs in a young, otherwise healthy person. The genetic abnormalities most associated with SCD are hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, long QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia. As a result of growing awareness that these deaths can be prevented, guidelines have been issued in both Europe and the United States to help screen and determine qualification for young persons who want to participate in competitive athletics. There remains debate on the how extensive screening should be, in particular over the use of the 12-lead electrocardiogram (ECG), with European guidelines mandating ECG and United States guidelines not recommending routine use of the ECG.

Brugada syndrome is a genetic cause of sudden cardiac arrest characterized by abnormal electrocardiographic (ECG) pattern in the right precordial leads either at rest or after provocation. In this condition, sudden death may occur due to polymorphic ventricular tachycardia or ventricular fibrillation. In approximately 30% of patients, sudden cardiac arrest is the initial clinical manifestation of Brugada syndrome. Treatment strategies for Brugada syndrome are evolving. Currently, the implanted cardioverter defibrillator (ICD) is the only proven treatment for Brugada syndrome. Candidates for ICD include patients include those with the type 1 ECG pattern or who have been successfully resuscitated from sudden death or have had unexplained syncope.

Congenital long QT syndrome is a genetic disorder characterized by prolonged QT interval on electrocardiogram and increased risk of sudden cardiac death from ventricular arrhythmias. In long QT syndrome, genes that encode for the various cardiac ion channels or regulatory proteins of these channels are mutated. The various mutations individually lead to a disruption of the normal cardiac myocyte action potential, and thus leading to a propensity for ventricular arrhythmias. Diagnosis can be difficult with patient presentations ranging from palpitations to syncope to sudden cardiac death. The QT interval can also vary over time, often requiring further testing to support the diagnosis. Recently developed genetic testing can be used to identify the responsible genes in patients with known disease. It can also be used to genotype the affected patient's family members. The current test panel only recognizes common mutations resulting in a falsely negative test for those with a rare or unidentified variant. For treatment, beta-blocker therapy is recommended for all patients, and implantable cardioverter-defibrillator (ICD) placement is recommended for those who are at high risk for a cardiac event. Future investigations will concentrate genotype-guided risk stratification for ICD placement and on genotype-specific pharmacological therapy.