Hypertrophic cardiomyopathy: individualized therapy for a heterogeneous disease.

It is now 50 years since the modern description of hypertrophic cardiomyopathy (HCM). The initial descriptions foretold the current efforts towards sudden death prevention, alleviation of heart failure symptoms and angina, relief of left ventricular outflow tract obstruction, preparticipation athletic screening, family screening and genetic testing. The authors review the salient features of HCM, focusing on therapeutic strategies to manage its symptoms and attempts to prevent sudden death.

Systolic anterior motion begins at low left ventricular outflow tract velocity in obstructive hypertrophic cardiomyopathy.

OBJECTIVES: The purpose of this study was to determine whether the dynamic cause for mitral systolic anterior motion (SAM) is a Venturi or a flow drag (pushing) mechanism. BACKGROUND: In obstructive hypertrophic cardiomyopathy (HCM), if SAM were caused by the Venturi mechanism, high flow velocity in the left ventricular outflow tract (LVOT) should be found at the time of SAM onset. However, if the velocity was found to be normal, this would support an alternative mechanism. METHODS: We studied with echocardiography 25 patients with obstructive HCM who had a mean outflow tract gradient of 82 +/- 6 mm Hg. We compared mitral valve M-mode echocardiogram tracings with continuous wave (CW) and pulsed wave (PW) Doppler tracings recorded on the same study. A total of 98 M-mode, 159 CW, and 151 PW Doppler tracings were digitized and analyzed. For each patient we determined the LVOT CW velocity at the time of SAM onset. This was done by first determining the mean time interval from Q-wave to SAM onset from multiple M-mode tracings. Then, CW velocity in the outflow tract was measured at that same time interval following the Qwave. RESULTS: Systolic anterior motion began mean 71 +/- 5 ms after Q-wave onset. Mean CW Doppler velocity in the LVOT at SAM onset was 89 +/- 8 cm/s. In 68% of cases SAM began before onset of CW and PW Doppler LV ejection. CONCLUSIONS: Systolic anterior motion begins at normal LVOT velocity. At SAM onset, though Venturi forces are present in the outflow tract, their magnitude is much smaller than previously assumed; the Venturi mechanism cannot explain SAM. These velocity data, along with shape, orientation and temporal observations in patients, indicate that drag, the pushing force of flow, is the dominant hydrodynamic force that causes SAM.

Medical treatment of hypertrophic cardiomyopathy.

Current medical therapy of hypertrophic cardiomyopathy (HCM) is tailored to relieve symptoms of exercise intolerance, angina, or syncope. In recent years, new concepts in the pathophysiology of HCM have evolved. These concepts underlie our medical therapy and are discussed first in this review. Subsequently, the agents available for the medical treatment of HCM are discussed, along with a practical strategy for rapid medical reduction of outflow gradients. The mechanism of benefit of negative inotropes for obstruction is described, and newer agents under investigation are discussed. Finally, antiarrhythmic therapy for troubling atrial and ventricular arrhythmias is considered.

Clinical and echocardiographic characteristics of left atrial spontaneous echo contrast in sinus rhythm.

OBJECTIVES: In this study we attempt to define the clinical and echocardiographic characteristics of patients with left atrial spontaneous echo contrast (LASEC) in sinus rhythm (NSR). BACKGROUND: Left atrial spontaneous echo contrast in atrial fibrillation (AF) is associated with increased risk of thromboembolism. Little is known about its significance in NSR. METHODS: We reviewed reports of 1,288 transesophageal echocardiogram (TEE) studies done with a 5 MHz probe. Patients with swirling LASEC who were in NSR during TEE were analyzed. We compared them with a control group of 45 age matched patients selected to have NSR, left atrium (LA) > 4.0 cm but no SEC. RESULTS: Spontaneous echo contrast in NSR was noted in 24 patients (2%) and formed our study group. All patients with SEC had enlarged LA, mean 5.6 cm +/- 0.6 cm. There was a higher prevalence of cerebrovascular accident (CVA) in patients with SEC when compared with controls with no SEC, 83% versus 56%, p = 0.02. Patients with SEC had larger LA, 5.6 versus 4.9 cm, p < 0.0001 and lower mean peak left atrial appendage emptying velocity (LAAEV), 38 versus 56 cm/s, p = 0.001. Thirteen percent of patients with SEC had LA thrombus as compared with none in the control group, p = 0.02. By multivariate analysis, SEC in NSR was found to be associated with CVA, larger LA size and decreased mean LAAEV. Even after adjusting for LA size, patients with SEC had a higher prevalence of CVA than controls, p = 0.03. CONCLUSIONS: Spontaneous echo contrast in NSR occurs in patients with significantly dilated LA and depressed atrial function. Left atrial thrombus is noted in 13% of such patients despite NSR. Spontaneous echo contrast in NSR is associated with a higher prevalence of CVA. Further, SEC is found to be an independent and more powerful correlate of CVA than reduced LAAEV or atrial size. These data indicate that LASEC in NSR is a prothombotic condition.

Mechanism of benefit of negative inotropes in obstructive hypertrophic cardiomyopathy.

BACKGROUND: Drugs with negative inotropic effect are widely used to decrease obstruction in hypertrophic cardiomyopathy (HCM). However, the mechanism of therapeutic benefit has not been studied. METHODS AND RESULTS: We used M-mode, two-dimensional, and pulsed Doppler echocardiography to study 11 patients with obstructive HCM before and after medical elimination of left ventricular outflow tract obstruction. We measured 148 digitized pulsed Doppler tracings recorded in the left ventricular cavity 2.5 cm apical of the mitral valve. Successful treatment slowed average acceleration of left ventricular ejection by 34% (P=.001). Mean time to peak velocity in the left ventricle was prolonged 31% (P=.001). Mean time to an ejection velocity of 60 cm/s was prolonged 91% (P=.001). Before treatment, left ventricular ejection velocity peaked in the first half of systole; after successful treatment, it peaked in the second half (P=.001). In contrast, after treatment, we found no change in peak left ventricular ejection velocity. We also found no change in the distance between the mitral coaptation point and the septum, as measured in two planes, indicating no treatment-induced alteration of this anatomic relationship. CONCLUSIONS: Medical treatment eliminates mitral-septal contact and obstruction by decreasing left ventricular ejection acceleration. By slowing acceleration, treatment reduces the hydrodynamic force on the protruding mitral leaflet and delays mitral-septal contact. This, in turn, results in a lower final pressure gradient.

Mid-systolic drop in left ventricular ejection velocity in obstructive hypertrophic cardiomyopathy--the lobster claw abnormality.

UNLABELLED: In many patients with obstructive hypertrophic cardiomyopathy, an abrupt mid-systolic drop in left ventricular ejection velocity can be detected. We analyzed 27 patients with obstructive hypertrophic cardiomyopathy who had 43 echocardiographic examinations (mean gradient 53 +/- 6 mm Hg). Exams showing a mid-systolic drop had higher mean outflow tract pressure gradients (90 +/- 6 compared with 29 +/- 4 mm Hg, p < 0.001). After medical elimination of obstruction, the mid-systolic drop was no longer seen. We measured 105 pulsed-wave Doppler tracings in the left ventricular cavity and compared them with 90 continuous-wave tracings through the outflow tract. There was a close temporal correlation between the nadir of the left ventricular velocity drop and the peak continuous-wave left ventricular outflow tract velocity (r = 0.99). There was also a close temporal correlation between the onset of the fall in pulsed velocity and the onset of M-mode mitral-septal contact (r = 0.95). CONCLUSIONS: The mid-systolic drop in left ventricular velocity is due to impedance to ejection and provides evidence of true obstruction. As left ventricular ejection velocity falls to its mid-systolic nadir because of impedance of ejection, velocity downstream in the left ventricular outflow tract actually rises to its peak. This disparity in the two velocities, deceleration in the left ventricular cavity and acceleration in the left ventricular outflow tract, indicates that the outflow orifice is progressively narrowed over time as the mitral valve is forced into the septum by the rising pressure difference. The obstruction phase is best described as a time-dependent, amplifying feedback loop. The orifice narrows over time because of the rising pressure difference; the pressure difference rises over time because of the narrowing orifice.

Onset during exercise of spontaneous coronary artery dissection and sudden death. Occurrence in a trained athlete: case report and review of prior cases.

This report describes a spontaneous coronary artery dissection occurring during exercise in a long-distance runner who otherwise had a normal coronary arteriogram. This syndrome has been reported before and the two previous cases are reviewed. Coronary dissection is a rare cause of death during exercise.

An echocardiographic study of the fluid mechanics of obstruction in hypertrophic cardiomyopathy.

OBJECTIVES: The goal of this study was to investigate the hydrodynamic cause of mitral-septal contact and obstruction in patients with hypertrophic cardiomyopathy. BACKGROUND: Mitral-septal apposition has been shown to be the cause of obstruction in patients with hypertrophic cardiomyopathy. With obstruction, characteristic continuous wave Doppler tracings show an increasing acceleration of flow. (Tracing is concave to the left.) METHODS: We studied 24 consecutive patients who had a Doppler echocardiographic pressure gradient > or = 36 mm Hg. We pursued two lines of inquiry. 1) Before the onset of obstruction, we systematically measured the angle between the direction of left ventricular Doppler color flow and the protruding mitral leaflet in early systole. 2) After the onset of obstruction, we qualitatively analyzed the concave contour of the continuous wave Doppler tracings in our patients and developed a hydrodynamic theory of the obstruction phase to explain the characteristic tracings. We present a mathematic model to support this concept. RESULTS: We measured 129 angles. Just before mitral-septal contact, the protruding mitral leaflet projects at a mean 40 degrees and 45 degrees relative to flow in the apical long-axis and apical five-chamber views, respectively. At mitral-septal contact, the obstructing leaflet projects at a mean 52 degrees and 58 degrees relative to flow in the same respective views. Even very early in systole, at leaflet coaptation, 11 of 23 patients had angles > 15 degrees relative to flow. After mitral-septal apposition, obstruction across a cowl-shaped orifice begins. During this stage, the obstructing leaflet projects at a mean 55 degrees and 63 degrees relative to flow. In 22 patients, the continuous wave Doppler tracing of the left ventricular outflow jet showed an increasing acceleration of flow. CONCLUSIONS: Just before mitral-septal contact, the protruding leaflets project at high angles relative to flow. At these high angles, flow drag, the pushing force of flow, is the dominant hydrodynamic force on the protruding leaflet and appears to be the immediate cause of obstruction. The high angle between flow direction and the protruding leaflet precludes significant Venturi effects. Even earlier in systole, at leaflet coaptation, flow drag is dominant in half of the patients, with angles relative to flow > 15 degrees. After obstruction is triggered, it appears from our data and model that the leaflet is forced against the septum by the pressure difference across the orifice. The increasing acceleration of Doppler flow is explained by a time-dependent amplifying feedback loop in which the rising pressure difference across the orifice leads to a smaller orifice and a higher pressure difference.

Successful medical therapy of mitral anular abscess complicating infective endocarditis.

A case of staphylococcal endocarditis with the echocardiographic findings of mitral anular abscess is described. The anular mass resolved after 9 weeks of antibiotic therapy. This case illustrates that perivalvular abscess complicating infective endocarditis may respond to medical therapy.

Value of two-dimensional echocardiography in evaluating coronary artery disease: a randomized blinded analysis.

Two-dimensional echocardiography at rest was used to analyze segmental wall motion abnormalities for detecting coronary artery disease in patients with and without a history of myocardial infarction. One hundred twenty-five echocardiograms were analyzed in a randomized, blinded fashion. They were obtained from 55 consecutive patients found to have significant coronary artery disease at angiography, 59 consecutive normal subjects and 11 patients with dilated cardiomyopathy. The overall sensitivity of two-dimensional echocardiography was relatively low at 67%. However, specificity was 99%. The sensitivity was higher in patients with past myocardial infarction than in those without myocardial infarction (81 versus 42%), as expected. Echocardiography can detect segmental wall motion abnormalities in some patients with coronary artery disease and no overt prior myocardial infarction. This was highlighted by nine such patients with coronary artery disease and no prior myocardial infarction or electrocardiographic Q waves who were found to have segmental wall motion abnormalities. A semiquantitative, two-dimensional echocardiographic segmental wall motion score was derived for 47 patients and was correlated with angiographic left ventricular ejection fraction (r = 0.71). This score differentiated patients with a normal ejection fraction (greater than 50%) from those with a depressed ejection fraction (less than 50%): 1.1 +/- 1.6 versus 6.9 +/- 3.1 (p less than 0.001). Almost all patients (92%) with an echocardiographic score of five or more had an abnormal ejection fraction of less than 50%. In patients with chronic congestive heart failure, the echocardiogram separated those with dilated cardiomyopathy from those with coronary artery disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Anomalous papillary muscle insertion contributing to obstruction in discrete subaortic stenosis.

A case of discrete subvalvular aortic stenosis with anomalous insertion of a papillary muscle to the base of the anterior mitral valve leaflet and continuous with the discrete subaortic stenosis is described. Two-dimensional echocardiographic and pathologic data showing the contribution of the anomalous papillary muscle to left ventricular outflow tract obstruction are presented.

Correlation of HLA types in premature coronary artery disease: an attempt to define independent genetic risk factors.

This study was designed to investigate whether isolated genetic factors, controlled by genes in the HLA chromosomal region, could be indicted as independent contributing influences in the genesis of premature coronary artery disease (CAD). Nineteen patients with fixed obstructive CAD documented by coronary angiography had no coronary risk factors with respect to age; levels of serum cholesterol, fasting triglycerides, and blood glucose; blood pressure; obesity; history of diabetes mellitus or hypertension; and cigarette-smoking history. Sixteen patients had a family history of CAD. HLA typing was restricted to antigens of the A and B loci. Control subjects (n = 1,157) were normal. At the A locus, no antigens demonstrated an observed frequency significantly higher than that expected from the control population. At the B locus, BW 38 had a statistically significant greater frequency (p less than 0.01) in the study group with CAD (21 percent) than in the control population (4 percent). The association between BW 38 and premature CAD lost its statistical significance when conservatively corrected for the number of HLA antigens tested by the Bonferroni adjustment. The relative risk for CAD if a patient had antigen BW 38 was 6.2. Our data suggest a statistically significant trend between the presence of HLA BW 38 and premature CAD. Whether the HLA tissue antigens are involved directly in the pathogenesis of CAD, act as markers for immune response genes, or serve as markers of other yet undefined genetic factors needs further study.