Louis A. Vismara

Relation of ventricular arrhythmias in the late hospital phase of acute myocardial infarction to sudden death after hospital discharge

To determine the prognostic significance of ventricular arrhythmias persisting during the hospital ambulatory phase of acute myocardial infarction, 64 patients with acute myocardial infarction underwent continuous 10-hour Holter monitoring an average of 11 days after discharge from the coronary care unit (CCU). Patients were categorized according to the results of ambulatory monitoring: 27 patients had ventricular extrasystoles, which were complicated (multifocal, R on T, paired, more than 5/min), or ventricular tachycardia; 22 had uncomplicated premature ventricular contractions; and 15 exhibited no ventricular arrhythmias. The 64 patients were followed prospectively for an average course of 25.8 months; 12 died suddenly; 8 died of other causes, and 44 survived. In all patients who died suddenly, ventricular ectopy was recorded on Holter monitoring before their discharge from the hospital (complicated premature ventricular contractions, eight patients; uncomplicated premature ventricular contractions, four patients); there were no sudden deaths in the patients without ventricular arrhythmias. Patients who died suddenly and those survived were similar in respect to age (60, 62 years), sex, location of infarction, presence of coronary risk factors, severity of acute myocardial infarction (Q waves, cardiac enzymes), serum cholesterol levels, evidence of cardiomegaly on roentgenograms, presence of ventricular gallop and drug therapy received. The occurrence of acute arrhythmias in the CCU did not separate patients who died suddenly from those who survived; there were no differences in ventricular tachycardia or ventricular fibrillation (3 or 12 patients who died suddenly, 6 of 44 patients who survived) or complicated premature ventricular contractions (4 or 12 patients who died suddenly, 18 of 44 patients who survived). Electrocardiograms obtained late in the hospital course revealed no differences in the extent of Q or T wave changes between these two groups. However, the extent of S-T segment abnormality was greater in patients who died suddenly than in patients who survived (5.6 compared to 1.8 leads/standard tracing, p smaller than 0.02) suggesting that the arrhythmias in the former were related to persistent ischemia or segmental ventricular dyssynergy. Thus, in this relatively small number of patients, ventricular arrhythmias persisting late in the hospital course of patients admitted for acute myocardial infarction are shown to predispose to subsequent sudden death.

Pharmacological mechanisms for left ventricular unloading in clinical congestive heart failure. Differential effects of nitroprusside, phentolamine, and nitroglycerin on cardiac function and peripheral circulation.

We compared cardiocircolatory actions of the com monly employed systemic vasodilators, intravenous (iv) nitroprusside (NP), Iv phentolamine (PH), and subliagoal nitroglycerin (NTG), causing left ventricular (LV) unloading in 29 chronic coronary subjects with congestive failure to determine whether they produce disparate responses in LV function by different relaxing actions on systemic resistance and capacitance beds. Each drug equally lowered systemic arterial pressures to a small extent, whereas heart rate rose slightly with NTG. Cardiac catbeterization showed a decline in end-diastolic pressure with NTG (19 to 8 mm Hg) which was greater (P < 0.05) than with NP and PH (21 to 11). Cardiac index increased (P < 0.05) during NP (2.68 to 2.93 liters/min per m2) and PH (2.60 to 3.02) but was unchanged (2.83) by NTG. Stroke work increased with PH, ejection fraction rose with NP and PH, and mean ejection rate increased with each, whereas pressure-time per minute fell and end-diastolic volume decreased with each agent. Total systemic vascular resistance declined (P < 0.001) during NP and PH (1,475 to 1,200 dynes sec cm-5) but was unchanged (1,487) by NTG. Plethysmographkally, forearm vascular resistance (FVR) decreased (P < 0.01) with NP and PH (61.6 to 39.1 mm Hg/ml per 100 g/min) bat not (52.4) by NTG. The decreases in venous tone (VT) with NTG (18.2 to 9.3 mn Hg/ml) and NP (183 to 9.8) were greater (P < 0.05) than with PH (18.8 to 13.1). FVR/VT percent changes of 0.%, 1.62, and 033 with NP, PH, and NTG indicated balanced systemic arteriolovenous relaxation by iv NP, greater arteriolar dilation with iv PH, and predominant venous dilation by sublingual NTG. Thus, vasodilators produce disparate modifications of LV function By their differing alterations of preload and impedance, which are dependent upon relative extents of relaxation of systemic resistance and capacitance vessels characteristic of each agent as used clinically.

Clinical use of sodium nitroprusside in chronic ischemic heart disease. Effects on peripheral vascular resistance and venous tone and on ventricular volume, pump and mechanical performance.

Although hemodynamic benefit has been shown with sodium nitroprusside (NP) in acute coronary pump failure, complete understanding of the mechanisms of action of the agent on the cardiocirculation and its value in chronic ventricular dysfunction are lacking. This investigation evaluates the effects of NP on the systemic and regional arterial and venous beds and on cardiac dynamics, ventricular volumes, contractile state and myocardial energetics in long-standing congestive heart failure. Twelve patients with chronic coronary pump dysfunction received NP infusion to lower systolic pressure to 95-105 mm Hg. Left ventricular (LV) function was assessed directly by angiographic volumes and high fidelity pressure, and peripheral circulatory dynamics were determined simultaneously by forearm arterial and venous plethysmography. NP reduced mean arterial pressure (MAP) from 88.2 to 73.4 mm Hg (P < 0.05) and significantly (P < 0.05) enhanced the variables of LV performance: LV end-diastolic pressure (EDP) diminished from 18.5 to 9.9 mm Hg; ejection fraction rose from 0.47 to 0.55; percent of LV segmental shortening increased; and isovolumic and ejection indices of contractility improved. Concomitantly, NP reduced the indices of myocardial oxygen demands of ventricular tension time index and LVED volume index. These salutary effects on LV performance and energetics occurred secondary to peripheral arterial and venous dilation (P < 0.05) produced by NP: total systemic vascular resistance was lowered from 1590 to 1310 dynes sec cm-5; forearm vascular resistance diminished from 46 to 37 mm Hg/ml/100 gm/min; and forearm venous tone fell from 14.2 to 10.1 mm Hg/cc. Depressed stroke index (SI) and cardiac index (CI) increased (P < 0.05) with NP, despite the fall in LVEDP, when ventricular filling pressures with the agent were at levels slightly above normal. Dextran infusion given with NP to restore LVEDP to moderately elevated values increased SI and CI (P < 0.05) when NP alone produced no change in stroke output. Thus, the peripheral vasodilator properties of nitroprusside improve LV function by reducing impedance to ventricular ejection, while MVO2 is diminished by decreasing LV preload and afterload through relaxing actions on both systemic arterial and venous smooth muscle. These LV unloading effects of nitroprusside in chronic congestive heart failure are most beneficial in patients with marked pump dysfunction and greatly elevated LVEDP and peripheral vascular resistance.

Arrhythmias in the Mitral Valve Prolapse Syndrome: Prevalence, Nature, and Frequency

Ambulatory monitoring and maximal treadmill exercise were compared in 40 normal subjects and 31 patients with mitral prolapse. A variable arrhythmia spectrum was observed in prolapse during monitoring: premature ventricular contractions in 18 (58%), supraventricular arrhythmias in 11 (35%), and bradyarrhythmias in 9 (29%). Significantly less arrhythmias occurred in normal subjects during monitoring: 10 (25%, P greater than 0.001), 3 (8%, P less than 0.001), 4 (10%, P less than 0.05), and 2 (5%, P less than 0.02), respectively. In patients with prolapse, arrhythmias occurred on resting electrocardiogram (ECG), 35% premature ventricular contractons, 6% supraventricular arrhythmias, and 10% bradyarrhythmias, and on treadmill exercise, 45%, 10%, and 3%; therefore, ambulatory monitoring was the most sensitive method of arrhythmia detection. No correlation existed between clinical features of prolapse and arrhythmias. Thus, arrhythmias occur in most patients with mitral prolapse, are not predictable by clinical characteristics, comprise a spectrum of ventricular and supraventricular tachyarrhythmias and bradyarrhythmias, and are best detected by ambulatory ECG monitoring.

Effects of nitroglycerin on left ventricular cavitary size and cardiac performance determined by ultrasound in man

Abstract Controversy remains whether the antianginal action of nitroglycerin is the result of change in coronary blood flow or decrease in myocardial oxygen demand (MVO 2 ) by decline in left ventricular systolic tension. Although left ventricular radius is an important determinant of left ventricular tension, clinical data have not been available on the effects of nitroglycerin on left ventricular cavitary size. Thus we evaluated the action of the organic nitrate on endocardial left ventricular dimensions determined by echograms. Left ventricular echoes were obtained just below the mitral valve in 6 normal subjects and in 14 patients with coronary disease before and at 2 minute intervals for 10 minutes after the sublingual administration of 0.6 mg nitroglycerin. Mean heart rate rose from 71 to 83 beats/min (p CF ) decreased from 1.08 to 1.02 circumferences/sec (p CF on head-up tilting. Since stroke volume fell in patients with minimal changes in heart rate whereas peripheral vascular resistance remained unaltered, the principal extracardiac dilator effect of nitroglycerin is on the systemic venous bed. Thus, sublingual administration of nitroglycerin in man reduces end-diastolic dimension and end-systolic dimension and thereby is capable of lowering MVO 2 by diminishing left ventricular tension. These findings support the concept that a decrease in MVO 2 plays an important role in the relief of angina pectoris by nitroglycerin.

Afterload reduction therapy with nitroprusside in severe aortic regurgitation: Improved cardiac performance and reduced regurgitant volume

To assess the hemodynamic effects of afterload reduction in severe aortic regurgitation, nitroprusside was infused at cardiac catheterization in 12 patients with aortic regurgitation. Cardiac hemodynamics, angiographic variables and regurgitant volumes were quantified during control periods, and nitroprusside was infused to reduce systemic systolic pressure to 110 to 125 mm Hg. The following were reduced by the drug: systolic arterial pressure (from 154 +/- 6.4 to 115 +/- 2.3 mm Hg, P less than 0.001); left ventricular end-diastolic pressure (from 23 +/- 2.2 to 11 +/- 1.0 mm Hg, P less than 0.001); systemic vascular resistance (from 1,782 +/- 133 to 1,148 +/- 94 dynes sec cm-5, P less than 0.001); left ventricular end-diastolic volume (from 242 +/- 25 to 196 +/- 19 ml, P less than 0.001); aortic regurgitant fraction (from 0.53 +/- 0.05 to 0.44 +/- 0.06, P less than 0.01); and aortic regurgitant minute volume (from 5.5 +/- 0.10 to 4.3 +/- 0.09 liters/min, P less than 0.01). Effective cardiac index increased (from 2.49 +/- 0.19 to 3.10 +/- 0.24 liters/min per m2, P less than 0.01), and left ventricular ejection fraction rose (from 0.55 +/- 0.03 to 0.61 +/- 0.03, P less than 0.005). These data indicate that afterload reduction with nitroprusside in severe aortic regurgitation improves cardiac performance, greatly decreases left ventricular preload and reduces aortic regurgitant volume. Thus, nitroprusside therapy has special value in severe aortic regurgitation that is of particular benefit in critical clinical conditions.

Chronic stable inferior myocardial infarction: unsuspected harbinger of high-risk proximal left coronary arterial obstruction amenable to surgical revascularization.

Eighty-four patients with previous uncomplicated isolated inferior myocardial infarction underwent coronary arteriography to determine the prevalence and distribution of coronary stenoses in order to identify those patients at high risk for early death. Coronary risk factors and treadmill stress testing were evaluated as predictors of left coronary artery disease, and the clinical course was compared of patients undergoing coronary bypass surgery versus those treated medically. Of the 84 patients, 17 (20 percent) had one vessel stenosis (75 percent or more luminal narrowing), 29 (35 percent) had stenosis of two and 38 (45 percent) had stenosis of all three major coronary arteries. Fifty-three patients (63 percent) had stenosis of the proximal left anterior descending coronary artery including 8 with complete and 18 with subtotal occlusion. Of the 53 patients with proximal left anterior descending arterial stenosis, 42 (79 percent) had an operable condition (no distal obstruction) as did 36 (69 percent) of 52 with circumflex arterial stenosis. Although the presence of multiple coronary risk factors, particularly with a positive stress test, was predictive of multivessel stenosis, lack of risk factors and a negative exercise test were nonspecific. Of 45 patients followed up for 18 months, 14 who underwent, coronary bypass surgery were compared with 31 medically treated patients with similar cardiac function and coronary pathoanatomy. Ten surgically treated patients (71 percent) had reduced angina compared with nine medically treated patients (29 percent) ( P P P > 0.05). Thus, serious left coronary artery disease is highly prevalent as well as operable in patients with chronic inferior myocardial infarction. The latter condition thereby provides a clinically useful and sensitive marker of high risk coronary arterial stenosis.

Identification of Sudden Death Risk Factors in Acute and Chronic Coronary Artery Disease

Because of their potential role in the pathogenesis of sudden death, cardiac arrhythmias in patients with coronary artery disease have become the subject of increasing concern and investigation. A series of studies on the problem of ventricular ectopy as it relates to the entire spectrum of sudden death in coronary disease were carried out utilizing continuous portable electrocardiographic monitoring systems. Evaluation of arrthymias during the entire 3 week in-hospital period after acute myocardial infarction in 83 patients revealed that absence of premature ventricular contractions, including their serious forms (multifocal, paired, R on T phenomenon, frequency 5/min or greater) and ventricular tachycardia in the coronary care unit did not exclude their high incidence rate (premature ventricular contractions 30 percent, serious forms 41 percent, ventricular tachycardia 6 percent) in the late hospital phase. Because late hospital serious forms of ventricular ectopy correlated with arterial hypoxia and elevated left ventricular filling pressure in the coronary care unit and with persistent S-T abnormalities, the extent of left ventricular dysfunction and ischemia with acute myocardial infarction appeared precursors to these arrhythmias. Study of ventricular ectopy in the late hospital phase of acute myocardial infarction indicated that ventricular ectopy and particularly its serious forms and prognostic significance relative to subsequent sudden death after discharge; the extent of predischarge S-T segment alterations was greater in subjects who died suddenly than in survivors, suggesting that persistent ischemia or segmental dyssynergy, or both, predisposed to lethal arrhythmias. Among 86 patients with chronic coronary disease documented by catheterizerization, 87 percent had ventricular ectopy and 62 percent serious ventricular arrhythmias, in contrast to 34 percent and 9 percent, respectively in normal subjects; frequency of serious forms of ventricular ectopy was related to extent of coronary atherosclerosis. Correlation of standard electrocardiograms with continuous Holter electrocardiograms in 101 patients with chronic coronary disease over 24 months revealed that the former modality was insensitive in arrhythmia detection; patients free of ventricular ectopy by serial standard electrocardiograms had a 62 percent incidence rate of serious forms of ventricular ectopy and 6 percent ventricular tachycardia on portable continuous monitoring. Additional studies of patients with chronic coronary disease showed that assessment of both the type of ventricular ectopy and the setting in which it occurs provides the most meaningful characterization of risk of sudden death. These systematic series of observations identify premature ventricular ectopic beats as important and separate risk factors in coronary disease...

Efficacy of Disopyramide Phosphate in the Treatment of Refractory Ventricular Tachycardia

The effects of intravenously administered disopyramide phosphate were evaluated in seven patients with refractory ventricular tachycardia. All patients had organic heart disease, including acute infarction (three patients), chronic coronary artery disease (two patients) and cardiomyopathy (two patients). The severity of the heart disease was reflected in the advanced patient age (average 64 years) and the occurrence before disopyramide therapy of cardiac arrest in five patients and congestive heart failure in all seven patients. In five patients, disopyramide was given as a bolus injection, 2 mg/kg body weight, followed by an infusion of 20 to 40 mg/hour. The final two patients received 4 mg/kg divided as a bolus injection and an infusion over 1 hour followed by a 0.4 mg/kg infusion during the next hour. Intravenous administration of disopyramide resulted in more effective electrical stability in all patients and completely eliminated ventricular tachycardia in six. Recurrence of ventricular tachycardia was prevented in six patients with subsequent long-term oral administration of disopyramide. Possible dose-related cardiac pump depression occurred in two patients, but disopyramide was otherwise well tolerated. Therefore, these data document the therapeutic efficacy of disopyramide in the treatment of refractory life-threatening ventricular tachyarrhythmias.

Pump dysfunction after myocardial infarction: Importance of location, extent and pattern of abnormal left ventricular segmental contraction

To delineate the relative effects on left ventricular function of the site, extent and nature of the abnormal left ventricular segmental contraction (dyssynergy) and thereby determine the mechanism by which anterior myocardial infarction results in greater depression of left ventricular performance than does inferior infarction, 43 patients with remote myocardial infarction of similar extent (average 38 percent of left ventricular systolic perimeter) and associated hypokinesia or dyskinesia confined to either the anterior or inferior wall were compared; 10 additional patients were evaluated who exhibited generalized dyssynergy (72 percent of left ventricular perimeter). When the pattern of dyssynergy and extent of infarction were similar, the location alone of dyssynergy did not influence variables of left ventricular function. However paradoxical outward systolic movement (dyskinesia) of the anterior or inferior wall resulted in greater depression (P less than 0.05) of measures of left ventricular performance than did diminished inward systolic motion (hypokinesia) associated with infarction of similar extent and location. All measures of left ventricular performance were considerably more depressed (P less than 0.05) in the 10 patients with generalized dyssynergy than in the 43 patients with localized dyssynergy. Thus, the location of infarction is not a unique determinant of left ventricular performance. Instead, the size of infarction is the principal characteristic of dyssynergy that impairs left ventricular function; the severity of the pattern of dyssynergy is significant but of lesser importance. It is therefore concluded that the greater reduction of left ventricular function in anterior than in inferior myocardial is largely the result of the more extensive area of necrosis rather than of the location of the infarction.