Lung ventilation-perfusion scintigraphy in pulmonary embolism. Diagnostic specificity compared to pulmonary angiography.

In 53 patients with possible pulmonary embolism, pulmonary abnormalities of 133Xe ventilation and 99Tcm albumin microsphere perfusion scintigraphy were compared with absence or presence of pulmonary emboli documented by concurrent pulmonary angiography. It was found that patients with combined scintigraphy considered as unlikely for pulmonary embolism (ventilation defect larger than perfusion defect) or indicative of pulmonary embolism (ventilation defect smaller than perfusion defect) provide high diagnostic specificity. Patients with equal ventilation-perfusion abnormalities (possible pulmonary embolism) require further evaluation by pulmonary angiography to ascertain diagnosis. Importantly, diagnostic accuracy, using ventilation-perfusion scintigraphy and the quantified method of evaluation delineated, is preserved in patients with severe congestive heart failure.

Hemodynamic assessment of the glutaraldehyde-preserved porcine heterograft in the aortic and mitral positions.

Although glutaraldehyde-preserved porcine heterograft (PH) valves may have a lowered incidence of thromboembolism compared to mechanical valves, data concerning postoperative function in PH valves are incomplete. Accordingly, 26 patients receiving PH in the aortic (AO) or mitral position (MIT) were studied at cardiac postoperative catheterization (mean 19 weeks). The 12 AO patients had an average peak systolic gradient of 19 mm Hg (range 3-52 mm Hg); mean valve area (VA) 1.33 cm2 (0.75-2.5; two patients had postoperative aortic insufficiency. The 14 MIT patients had a mean gradient of 7.9 mm Hg (0-13.1); VA 1.84 cm2 (0.70-3.2; postoperative mitral regurgitation occurred in two patients. AO stent diameter (SD) related to VA, r = 0.85; and peak gradient, r = -0.75. However, MIT SD did not relate to VA or peak gradient. At the 14-month follow-up examination 9 of 11 AO and 7 of 11 MIT patients improved by at least one functional class. Thus, with the advantage of reduced thromboembolism and generally satisfactory valve hemodynamics, further clinical trial of glutaraldehyde-preserved porcine heterografts is justified.

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.

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...

Improved longevity due to reduction of sudden death by aortocoronary bypass in coronary atherosclerosis.

To evaluate the efficacy of coronary bypass surgery in reduction of sudden death, the prognosis of 286 similar patients with multivessel coronary stenosis was studied prospectively and the results of medical therapy (Group I, 114 patients) were compared with those of surgical therapy (Group II, 172 patients) after cardiac catheterization and coronary arteriography. During 39 months' evaluation of both groups, mortality from congestive heart failure and noncardiac causes did not differ (Group I, 14 percent; Group II, 8 percent) (P greater than 0.05). Sudden was evaluated in the remaining 217 patients (Group I, 96; Group II, 121 patients) who were matched for age (Group I, 52 years; Group II, 51 years); duration of overt coronary disease (Group I, 3.8 years; Group II, 4.0 years); angina pectoris (Group I, 83 percent; Group II, 95 percent); prior myocardial infarction (Group I, 77 percent; Group II, 74 percent); and congestive heart failure (Group I, 30 percent; Group II, 23 percent) (all P greater than 0.05). In addition, the prevalence of coronary risk factors was the same (P greater than 0.05) in both groups (hypertension, cigarette smoking, diabetes mellitus, lipid abnormalities and family history of coronary disease). Importantly, arteriography and catheterization established a similar extent and location of major coronary arterial stenoses and of ventricular dysfunction; two vessel disease (Group I, 32 percent; Group II, 33 percent) and three vessel disease (Group I, 68 percent; Group II, 67 percent); left ventricular end-diastolic pressure (Group I, 13; Group II, 14 mm Hg);cardiac index (Group I, 2.85; Group II, 2.91 liters/min per m2); and coronary collateral vessels (Group I, 58 percent; Group II, 61 percent) (all P greater than 0.05). Fifty-six percent of patients in Group II had multiple bypass grafts and a late patency rate (average 21 months) of 87 percent of one or more grafts. During subsequent prospective evaluation of over 3 years, bypass surgery provided greater symptomatic benefit of improved functional capacity (Group I, 12 percent; Group II, 69 percent) (P less than 0.05) and complete anginal relief (Group I, 30 percent; Group II, 60 percent) (P less than 0.05). Moreover, bypass surgery was associated with marked reduction in sudden death (Group I, 24 percent; Group II, 6 percent) (P less than 0.05). Thus, in patients with multivessel coronary disease carefully matched for clinical factors, hemodynamics, atherogenic precursors and coronary pathoanatomy, effective aortocoronary bypass surgery appeared to prolong survival by decreasing the incidence of sudden death, possibly by a decrease of unexpected fatal arrhythmias.

Multifactor evaluation of the determinants of ischemic electrocardiographic response to maximal treadmill testing in coronary disease.

Despite widespread use of treadmill stress in the detection of coronary disease, detailed information relating the important features of coronary pathoanatomy to the ischemic response noted on the electrocardiogram is lacking. Accordingly, 91 consecutive patients undergoing graded maximal exercise tests (MEXT) who were found to have clinical stenosis (larger than or equal to 75 per cent luminal narrowing) of at least one of the three major coronary arteries on coronary arteriography were evaluated. Positive MEXT was defined as larger than or equal to 0.1 mV horizontal or downsloping S-T segment depression larger than or equal to 0.08 second beyond J point. Over-all sensitivity of positive MEXT was 59 of 91 (65 per cent) patients; 11 of 26 (42 per cent) with single vessel stenosis, 20 of 30 (66 per cent) with two vessel disease and 28 of 35 (80 per cent) with three vessel disease. In patients with two vessel disease, the frequency (p less than 0.05) of positive MEXT was greater in those with (15 of 21;71 per cent) than in those without (five of nine; 55 per cent) stenosis of the left anterior descending artery. Concerning the site of intravessel stenosis, the frequency of positive MEXT was greater (p less than 0.05) with stenosis proximal to the left anterior descending artery in patients with one vessel disease. Quantification of total numbers of intra- and intervessel stenoses revealed 2.7 stenoses in the 59 patients with positive MEXT in contrast (p less than 0.01) to 1.9 in 32 patients with negative MEXT. Similarly, graded luminal narrowing index of severity of total stenoses per patient was 9.9 in those with positive MEXT compared (p less than 0.01) to 6.1 in those with negative MEXT. The poststenotic myocardial perfusion index, estimated by graded distal vessel opacification per major vessel disease, was only 1.5 in those with positive MEXT contrasted (p less than 0.01) to 2.4 in those with negative MEXT. These data indicate that sensitivity of positive MEXT in patients with coronary disease is most closely determined by the number of major coronary vessels involved, the total number of major vessels stenosed, the severity of total stenoses and poststenotic distal vessel perfusion. Less important factors are the precise site of intravessesl stenosis and the specific major coronary artery involved, although stenosis proximal to the left anterior descending artery favored positive MEXT. Unimportant variables were the quality of collateral vessels, ventricular function and prior inferior infarction. Angina occurred more frequently in those with positive MEXT, and marked degree of positive MEXT indicated stenosis proximal to the left anterior descending artery.

Improvement of symptoms in patients with sick sinus syndrome by spontaneous development of stable atrial fibrillation.

Fifty-six patients with symptomatic chronic sinus bradycardia because of sick sinus syndrome (SSS) were followed for periods from one month to 11 years (average 3-2 years). Eleven developed stable atrial fibrillation persisting for 8 to 61 months; 52 had permanent demand pacemakers implanted before atrial fibrillation commenced. In the 11 patients with atrial fibrillation, 10 had adequate ventricular rate, 8 with rates greater than 100 beats/min requiring digoxin for rate control. The 8 patients with atrial fibrillation with pacemakers remained asymptomatic for 13 to 18 months without requiring reimplantation; battery failure occurred in 2 whose rapid ventricular rates were controlled by digoxin. In the other 6 patients with pacemakers who developed atrial fibrillation, adequate ventricular rates persisted resulting in overdrive suppression. No patient had systemic embolisation. The previous duration of symptomatic sinus bradycardia was longer in patients developing atrial fibrillation (average 5-5 years) compared (P less than 0-01) with patients without atrial fibrillation (1-9 years). Further, premature atrial contractions occurred in all 11 patients before atrial fibrillation in contrast to only 21 of the 45 patients without atrial fibrillation. It is concluded that occurrence of atrial fibrillation in SSS with symptomatic sinus bradycardia provides a natural cure of symptoms caused by bradycardia. These data indicate that permanent ventricular pacing may not be necessary if persistent atrial fibrillation develops in SSS.

The effects of morphine on isolated cutaneous canine vascular smooth muscle.

In order to evaluate the direct effects of morphine sulfate (MS) on vascular smooth muscle (VSM), a helical strip preparation of canine cutaneous VSM was prepared from vessels of approximately 150 to 250 mug internal diameter. When evaluated at a variety of muscle lengths from 20% to 60% above unstretched length, in the absence and in the presence of norepinephrine (2 to 10x10(-4) mg/cc), MS (10(-3) to 10(-1) mg/cc) failed to produce any noticeable effect. Thus, the well-known arteriolar dilator effect of MS is not a direct effect of the drug on VSM and it is not secondary to blockade of vascular alpha-adrenergic receptors.

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.

The effects of morphine on venous tone in patients with acute pulmonary edema.

In order to compare the venodilation effect of morphine in normal individuals (22) with that in patients (13) with heart failure morphine sulfate (0.1 mg/kg) was administered to 13 patients with mild pulmonary edema. After morphine congestive symptoms improved and venodilation was induced as determined by two independent techniques: venous pressure fell 10.2 mm Hg by the isolated hand technique and the venous volume of the forearm increased by 0.48 cc/100 ml, measured by equilibration technique. Neither finding differed from those in normal individuals. Reflex venoconstriction noted on the taking of a single deep breath was unaffected by morphine administration and was similar to that observed in normal subjects. Since the drug morphine sulfate does not cause a major pooling of blood in the limbs, the favorable effect of narcotics in patients with pulmonary edema must be caused by other mechanisms such as splanchnic pooling, afterload reduction or reduced breathing effort.

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 cardiocirculatory actions of the commonly employed systemic vasodilators, intravenous (iv) nitroprusside (NP), iv phentolamine (PH), and sublingual 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 catheterization showed a decline in end-diastolic pressure with NTG (19 to 8 mm Hg) which was greater (P less than 0.05) than with NP and PH (21 to 11). Cardiac index increased (P less than 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 less than 0.001) during NP and PH (1,475 to 1,200 dynes sec cm-5) but was unchanged (1,487) by NTG. Plethysmographically, forearm vascular resistance (FVR) decreased (P less than 0.01) with NP and PH (61.6 to 39.1 mm Hg/ml per 100 g/min) but not (52.4) by NTG. The decreases in venous tone (VT) with NTG (18.2 to 9.3 mm Hg/ml) and NP (18.5 to 9.8) were greater (P less than 0.05) than with PH (18.8 to 13.1) FVR/VT percent changes of 0.96, 1.62, and 0.53 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.

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.

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.