Mark L. Smucker

Comparison of outcome of asymptomatic to symptomatic patients older than 20 years of age with valvular aortic stenosis

A 2-part prospective study was performed to evaluate the clinical outcome of patients with hemodynamically confirmed asymptomatic valvular aortic stenosis (AS). During phase 1, linear regression analysis showed continuous wave Doppler to be highly accurate in predicting catheterization measured peak systolic aortic valve pressure gradients in 101 consecutive patients aged 36 to 83 years (mean 65 +/- 8) with symptomatic AS. During phase 2, 90 additional patients (51 asymptomatic and 39 symptomatic) with Doppler-derived peak systolic aortic valve gradients greater than or equal to 50 mm Hg (range 50 to 132 [mean 68 +/- 19]) were followed for 1 to 45 months. Both groups of patients in phase 2 had similar Doppler gradients and clinical and auscultatory evidence of moderate to severe AS at baseline. Asymptomatic patients were younger (p = 0.01), had higher ejection fractions (p = 0.001) and were less likely to have an electrocardiographic strain pattern (p = 0.01) and left atrial enlargement (p = 0.02). End-diastolic wall thickness, left ventricular cross-sectional myocardial area and estimated left ventricular mass were 18% (p = 0.0001), 20% (p = 0.0008), and 29% (p = 0.002) greater in symptomatic patients. During 17 +/- 9 months of follow-up, 21 asymptomatic patients (41%) became symptomatic. Dyspnea was the most common initial complaint, occurring 2.5 and 4.8 times more often than angina and syncope, respectively. Compared with the 39 symptomatic patients, the 51 asymptomatic patients had a lower cumulative life table incidence of death from any cause (p = 0.002), and from cardiac causes (p = 0.0001) including sudden death (p = 0.013).(ABSTRACT TRUNCATED AT 250 WORDS)

Prediction of outcome after mitral valve replacement in patients with symptomatic chronic mitral regurgitation. The importance of left atrial size.

BackgroundThe ability to predict outcome after mitral valve replacement remains limited in patients with symptomatic chronic mitral regurgitation. The aims of this study were to determine the preoperative predictors of postoperative cardiac-related mortality and to assess the additive prognostic value of tests performed in such patients. Methods and ResultsAccordingly, 176 patients (mean age, 57 ± 14 years) who underwent mitral valve replacement were followed up for 3.8 ± 0.5 years. Four categories of variables were analyzed to predict postoperative cardiac-related mortality: clinical, laboratory, two-dimensional echocardiographic (2DE), and cardiac catheterization. There were 39 cardiac-related deaths (29 due to congestive heart failure and 10 sudden). When the four categories were analyzed separately, two clinical, one laboratory, two 2DE, and one catheterization variable best predicted postoperative death. When these six variables were examined simultaneously, only three (one clinical and two 2DE) remained significant predictors of cardiac-related mortality: presence of pulmonary rales, left atrial size, and the ratio of left ventricular wall thickness to left ventricular cavity dimension in end systole. A model based on these three variables may predict cardiac-related death with considerable accuracy. Laboratory data did not add to clinical information for predicting death. 2DE variables provided significant additional information in this regard (p < 0.001). Further addition of catheterization variables was not useful. Prognostic value did not change significantly when 50 patients with prior mitral valve surgery or 49 patients undergoing concomitant aortic valve replacement or coronary artery bypass surgery were excluded from analysis. ConclusionsWe conclude that 1) measures of both left ventricular systolic function and leftatrial size are equally important in predicting postoperative cardiac-related mortality in patients with symptomatic chronic mitral regurgitation undergoing mitral valve replacement; 2) left atrial size may be important because it reflects the “history” (severity and duration) of mitral regurgitation; 3) 2DE assessment. of left atrial size and left ventricular function provides prognostic information that is significantly greater than that obtained from clinical and laboratory parameters alone; the addition of catheterization variables does not increase the prognostic value of the clinical and 2DE data. (Circulation 1991;84:23–34)

Myocardial contrast echocardiography in humans. II. Assessment of coronary blood flow reserve

The hypothesis that myocardial contrast echocardiography could be used to simultaneously assess coronary blood flow reserve and the size of the perfusion bed supplied by a coronary artery was examined in nine patients and six dogs. All patients were undergoing cardiac catheterization and had single vessel coronary artery disease (greater than or equal to 85% stenosis of either the proximal left anterior descending or the left circumflex coronary artery); the six dogs had a critical stenosis of the left circumflex coronary artery. Three milliliters of sonicated Renografin-76 (mean microbubble size 6 micron) was injected into the left main coronary artery before and after intracoronary administration of papavarine, 6 to 9 mg. The beds supplied by the normal and stenotic vessels could not be differentiated during contrast echocardiography before injection of papavarine. However, after papavarine, the normal vascular bed showed significantly more contrast enhancement than did the bed supplied by the stenotic artery. This disparity in contrast enhancement made it possible to delineate the size of the bed perfused by the stenotic vessels. When quantitative analysis of the time-intensity curves obtained from the echocardiograms was performed in the dogs, the absolute values for the area under the curve, peak contrast intensity and curve width did not correlate with absolute blood flows measured with radiolabeled microspheres. However, the ratios of the areas under the curves derived from the two vascular beds before and after papavarine correlated well with the ratios of blood flows between the two beds during the same stages (r2 = 0.73 by linear regression and r2 = 0.85 by an exponential function). In comparison, the ratios of peak amplitudes and curve widths before and after papavarine had poor correlations with ratios of flows from the two beds (r2 = 0.18 and 0.02, respectively). In conclusion, myocardial contrast echocardiography can be used to simultaneously assess coronary blood flow reserve and the size of the perfusion bed supplied by a stenotic vessel.

Usefulness of bucindolol in congestive heart failure

The sympathetic hyperactivity of congestive heart failure (CHF) may worsen cardiovascular function by down-regulation of myocardial beta-receptors. For this reason, beta blockade is proposed to be useful in CHF. Bucindolol is a new beta blocker that has intrinsic nonadrenergically-mediated vasodilation and may be valuable in treatment of CHF. To test this, 19 patients with CHF were randomized in a double-blind protocol to 3 months of treatment with bucindolol (n = 12) or placebo (n = 7). Significant improvement was seen in the bucindolol group using invasive and noninvasive tests; treadmill time increased from 445 to 530 seconds (p = 0.04), Minnesota Living With Heart Failure Questionnaire score improved from 61 to 40 (p = 0.0001), cardiac output increased from 4.0 to 4.7 (p = 0.02), and systemic vascular resistance decreased from 1,888 to 1,481 (p = 0.04). Also, peak exercise heart rate and pulmonary capillary wedge pressure decreased significantly with treatment. There were no changes in the placebo group. We conclude that bucindolol may be an effective treatment for CHF when administered chronically and that its nonadrenergic vasodilation may be an important feature.

Myocardial contrast echocardiography in humans: I. Safety—A comparison with routine coronary arteriography

Myocardial contrast echocardiography is a new diagnostic cardiovascular imaging technique capable of defining perfusion zones of coronary vessels in vivo; ultimately, it may be used to measure absolute regional myocardial blood flow. However, before it can be used in humans, its safety must be clearly established. Accordingly, the electrocardiographic and hemodynamic effects of intracoronary injections of 2 cc of sonicated Renografin-76 were compared with 5 to 10 cc of non-sonicated Renografin-76 in 10 subjects with normal coronary arteries. Two cubic centimeters of sonicated Renografin provides optimal myocardial opacification during echocardiography, while 5 to 10 cc of Renografin is required for an adequate coronary arteriogram. During coronary arteriography, heart rate decreased while PR and QT intervals and QRS duration increased as compared with baseline and myocardial contrast echocardiography (p less than 0.01). Similarly, the decrease in aortic pressure and first derivative of left ventricular pressure (dP/dt) was significantly (p less than 0.01) greater during routine coronary arteriography than during myocardial contrast echocardiography. Changes in left ventricular end-diastolic or pulmonary capillary wedge pressure were similar during myocardial contrast echocardiography and coronary angiography. There were no significant differences in the duration of electrocardiographic and hemodynamic changes between myocardial contrast echocardiography and coronary arteriography. It is concluded that intracoronary injection of 2 cc of sonicated Renografin-76 provides optimal myocardial opacification. It is safe in humans, producing transient electrocardiographic and hemodynamic alterations that are less pronounced than those seen during routine coronary angiography.

Is tau a preload-independent measure of isovolumetric relaxation?

Several studies have been performed in patients with a variety of myocardial diseases that have identified a prolongation of tau. However, it is not clear whether prolongation of tau represents abnormal myocardial physiology or the effect of excessive load associated with a particular disease process. Accordingly, we evaluate the effect on tau of an isolated decrease in preload induced by inferior vena cava occlusion before the appearance of reflex changes in six patients designated as normal by catheterization criteria. A computer-based digitization routine identified cardiac contractions in all patients early after inferior vena cava occlusion where left ventricular end-diastolic pressure decreased (18.3 +/- 6.3 to 9.3 +/- 5.8, p less than 0.05) while left ventricular systolic pressure (113.3 +/- 13.8 to 111.8 +/- 14.0, p = NS) and heart rate (66.0 +/- 10.0 to 65.9 +/- 10.3, p = NS) did not change. After this alteration in preload, no change in tau from baseline, as calculated by the logarithmic (TL), derivative (TD), or method of Mirsky (T1/2), was noted: TL, 47.4 +/- 6.5 to 44.6 +/- 7.6; TD, 39.3 +/- 8.1 to 39.8 +/- 8.4; T1/2, 33.0 +/- 4.0 to 31.8 +/- 4.6; all p = NS. The baseline pressure extrapolated from isovolumetric relaxation did not change in these preload beats compared with baseline (+4.26 +/- 6.20 to -0.80 +/- 4.87, p = NS). Subsequent beats were identified where left ventricular systolic pressure showed a numeric decrease compared with baseline (113.3 +/- 13.8 to 100.8 +/- 14.3, p = NS) despite no change in heart rate (66.0 +/- 10.0 to 66.8 +/- 10.5, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Overestimation by Doppler echocardiography of pressure gradients across starr-edwards prosthetic valves in the aortic position

Abstract The accuracy of continuous wave Doppler for estimating transvalvular pressure gradients in patients with aortic stenosis has been verified 1–3 ; however, few data are available regarding the precision with which gradients across prosthetic valves in the aortic position can be determined by Doppler. Two available relevant reports 4,5 describe a total of 12 patients studied by both Doppler and cardiac catheterization but include only a single Starr-Edwards (S-E) aortic prosthesis. We report our experience with measurement of pressure gradients across aortic S-E valves by continuous wave Doppler in 6 consecutive patients who also underwent transseptal cardiac catheterization at our hospitals.

Naturally occurring cardiomyopathy in the Doberman pinscher: A possible large animal model of human cardiomyopathy?☆

Currently there is no large animal model of dilated cardiomyopathy. The smaller animal models of cardiomyopathy, such as the Syrian hamster, cannot be studied with echocardiography and cardiac catheterization, and the relevance of these models to human dilated cardiomyopathy is open to question. On the basis of some initial observations in Doberman pinschers, it was speculated that these dogs could have occult left ventricular dysfunction. Accordingly, studies were performed in 46 apparently healthy Doberman pinschers and in 41 mongrel dogs: two-dimensional echocardiography (30 dogs in each group), cardiac catheterization (16 Doberman pinschers and 12 mongrels) and coronary blood flow studies (13 Doberman pinschers and 6 mongrels). In the awake, unsedated dogs studied with echocardiography, left ventricular wall thickening was significantly less in the Dobermans than in the mongrels (28% versus 36%, p = 0.0003). In the anesthetized dogs undergoing cardiac catheterization, left ventricular ejection fraction was significantly lower in the Dobermans than in the mongrels (0.38 versus 0.63, p = 0.0001). Rest coronary blood flow and coronary blood flow reserve were similar in the two groups. It is concluded that apparently healthy Doberman pinschers have occult left ventricular dysfunction. These dogs may serve as a large animal model of dilated cardiomyopathy and should not be used experimentally to study normal cardiac physiology.

Short-term infarct vessel patency with aspirin and dipyridarnole started 24 to 36 hours after intravenous streptokinase

The duration of intravenous heparin therapy required to maintain patency of the infarct-related artery after intravenous streptokinase is uncertain. Twenty-eight patients were prospectively treated with 1.5 million units of intravenous streptokinase within 4 hours of onset of chest pain. Intravenous heparin was begun after the streptokinase infusion was complete and was discontinued within 36 hours. Aspirin, 325 mg daily, and dipyridamole, 75 mg three times a day, was begun before the heparin was discontinued. Coronary angiography was performed both at 2 hours after completion of the streptokinase infusion and again at a mean of 8.7 (+/- 3.2) days after the initial catheterization. One patient died after treatment with streptokinase but before early angiography. In 21 of 27 patients (78%), Thrombolysis in Myocardial Infarction trial (TIMI) grade 2 or 3 perfusion in the infarct vessel was observed on initial angiography. Repeat angiograms were available in 17 of the 21 patients with initially patent vessels. Continued patency (TIMI grade 2 or 3) was found in 15 of the 17 patients (88%). Two of the four patients who did not undergo repeat angiography died, and the remaining two patients required coronary artery bypass grafting for unstable angina. Bleeding complications occurred in 6 of 27 patients (22%), with two (7%) requiring surgical evacuation of a groin hematoma. There were no instances of intracerebral bleeding and only two patients required transfusions. Thus, the combination of aspirin and dipyridamole following 36 hours of systemic heparinization after intravenous streptokinase infusion is associated with a reocclusion rate comparable to that which has been reported for more prolonged systemic anticoagulation with fewer hemorrhagic complications.

Left ventricular dysfunction in excess of the size of infarction: A possible management strategy

In this report we describe two patients whose left ventricular dysfunction was far in excess of infarct size as evidenced by ECG changes and the magnitude of creatine kinase release. Both patients demonstrated redistribution in myocardial beds remote from the infarct zone on delayed rest thallium 201 images and both had multivessel disease evident on coronary angiography. Both patients experienced relief of symptoms and improvement in regional and global left ventricular function after revascularization surgery. The possible mechanisms of left ventricular dysfunction in myocardial beds remote from the zone of infarction are discussed.