Robert O. Bonow

Myocardial ischemia in patients with hypertrophic cardiomyopathy: contribution of inadequate vasodilator reserve and elevated left ventricular filling pressures.

To study the mechanism and hemodynamic significance of myocardial ischemia in hypertrophic cardiomyopathy, 20 patients (nine with resting left ventricular outflow tract obstruction greater than or equal to 30 mm Hg) with a history of angina pectoris and angiographically normal coronary arteries underwent a pacing study with measurement of great cardiac vein flow, lactate and oxygen content, and left ventricular filling pressure. Compared with 28 control subjects without hypertrophic cardiomyopathy, their resting coronary blood flow was higher (91 +/- 27 vs 66 +/- 17 ml/min; p less than .001) and their coronary resistance was lower (1.13 +/- 0.38 vs 1.55 +/- 0.45 mm Hg/ml/min; p less than .001). Left ventricular end-diastolic pressure (16 +/- 6 vs 11 +/- 3 mm Hg; p less than .001) and pulmonary arterial wedge pressure (13 +/- 5 vs 7 +/- 3 mm Hg; p less than .001) were significantly higher in patients with hypertrophic cardiomyopathy. During pacing, coronary flow rose in both groups, although coronary and myocardial hemodynamics differed greatly. In contrast to the linear increase in flow in control subjects up to heart rate of 150 beats/min (66 +/- 17 to 125 +/- 28 ml/min), patients with hypertrophic cardiomyopathy demonstrated an initial rise in flow to 133 +/- 31 ml/min at an intermediate heart rate of 130 beats/min. At this point, 12 of 20 patients developed their typical chest pain. With continued pacing to a heart rate of 150 beats/min, mean coronary flow fell to 114 +/- 29 ml/min (p less than .002), with 18 of 20 patients experiencing their typical chest pain and metabolic evidence of myocardial ischemia. This fall in coronary flow was associated with a substantial rise in left ventricular end-diastolic pressure (30 +/- 9 mm Hg immediately after peak pacing). In the 14 patients whose coronary flow actually fell from intermediate to peak pacing, the rise in left ventricular end-diastolic pressure in the same interval was greater than that of the six patients whose flow remained unchanged or increased (11 +/- 8 vs 2 +/- 2 mm Hg; p less than .01). In addition, despite metabolic and hemodynamic evidence of myocardial ischemia, the arteriovenous O2 difference actually narrowed at peak pacing. Thus most patients with hypertrophic cardiomyopathy achieved maximum coronary vasodilation and flow at modest increases in heart rate. Elevation in left ventricular filling pressure, probably related to ischemia-induced changes in ventricular compliance, was associated with a decline in coronary flow.(ABSTRACT TRUNCATED AT 400 WORDS)

Myocardial perfusion abnormalities in patients with hypertrophic cardiomyopathy: assessment with thallium-201 emission computed tomography.

Myocardial ischemia may play a critical role in the symptomatic presentation and natural history of hypertrophic cardiomyopathy (HCM). To assess the relative prevalence and functional significance of myocardial perfusion abnormalities in patients comprising the broad clinical spectrum of HCM, we studied 72 patients (ages 12 to 69 years, mean 40) using thallium-201 emission computed tomography. Imaging was performed immediately after maximal exercise and again after a 3 hr delay. Regional perfusion defects were identified in 41 of the 72 patients (57%). Fixed or only partially reversible defects were evident in 17 patients, 14 of whom (82%) had left ventricular ejection fractions of less than 50% at rest. Twenty-four patients demonstrated perfusion defects during exercise that completely reversed at rest; all had normal or hyperdynamic left ventricular systolic function (ejection fraction greater than or equal to 50%). Perfusion abnormalities were present in all regions of the left ventricle. However, the fixed defects were observed predominantly in segments of the left ventricular wall that were of normal or only mildly increased (15 to 20 mm) thickness; in contrast, a substantial proportion (41%) of the completely reversible defects occurred in areas of moderate-to-marked wall thickness (greater than or equal to 20 mm, p less than .001). Neither a history of chest pain nor its provocation with treadmill exercise was predictive of an abnormal thallium study, since regional perfusion defects were present in 10 of 18 (56%) completely asymptomatic patients, compared with 31 of 54 (58%) symptomatic patients. These data indicate that myocardial perfusion abnormalities occur commonly among patients with HCM. Fixed or only partially reversible defects suggestive of myocardial scar and/or severe ischemia occur primarily in patients with impaired systolic performance. Completely reversible perfusion abnormalities occur predominantly in patients with normal or supranormal left ventricular systolic function. Such dynamic changes in regional thallium activity may reflect an ischemic process that contributes importantly to the clinical manifestations and natural history of HCM.

Valve replacement for regurgitant lesions of the aortic or mitral valve in advanced left ventricular dysfunction.

Patients with aortic regurgitation and severe left ventricular dysfunction remain candidates for aortic valve replacement, as long as the risks of late left ventricular dysfunction and congestive heart failure have been fully discussed with the patient, the patients family, and the referring physician. In contrast, patients with mitral regurgitation and severe systolic dysfunction are at considerable risk of more severe left ventricular dysfunction after operation, especially if mitral valve repair or chordal-sparing procedure cannot be performed. In patients who are candidates for such procedures that preserve the integrity of the subvalvular mitral apparatus, operation may be successful in selected patients despite moderate-to-severe depression of systolic function. Prognosis is guarded to poor in patients with regurgitant valvular lesions and advanced left ventricular dysfunction, and the emerging alternative treatments discussed in other articles in this Cardiology Clinics deserve consideration in these patients.

Effects of sublingual nifedipine on hemodynamics and systolic and diastolic function in patients with hypertrophic cardiomyopathy.

The hemodynamic effects of sublingual nifedipine were examined in 36 patients with hypertrophic cardiomyopathy. Twenty-one patients were initially given 20 mg and 15 patients were given 10 mg of the drug; 30 min after this first dose 26 patients received 10 mg and one patient 20 mg as a second dose. Hemodynamic findings in patients who received different doses of the drug were similar. Peak effects included an increase in heart rate from 79 +/- 12 to 91 +/- 14 (mean +/- 1 SD) beats/min (p less than .01), and a decrease in mean blood pressure from 89 +/- 12 to 77 +/- 10 mm Hg (p less than .01). Cardiac index increased after nifedipine (2.8 +/- 0.6 to 3.3 +/- 0.8 liters/min/m2; p less than .01); stroke volume index, however, did not change (36 +/- 7 to 36 +/- 8 ml/beat/m2; NS). Peripheral vascular resistance index fell significantly from 822 +/- 261 to 610 +/- 197 dynes X sec X cm-5 (p less than .01). Overall, left ventricular outflow tract gradient (LVOTG) did not change in patients with significant (greater than or equal to 30 mm Hg) basal LVOTG (75 +/- 22 to 83 +/- 22 mm Hg; NS), but it increased significantly in those six patients in whom peripheral vascular resistance fell by 25% or more (73 +/- 28 to 99 +/- 22 mm Hg; p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)