Experimental myocardial infarction. XVI. The detection of inotropic contractile reserve with postextrasystolic potentiation in acutely ischemic canine myocardium.

Postextrasystolic potentiation after a single closely coupled extrasystole may identify residual ventricular contractile performance in acutely ischemic myocardium without producing sustained secondary ischemic depression of myocardial function. Postextrasystolic potentiation was systematically used in eight open chest dogs to assess the progression of regional contraction abnormalities during a 10 minute occlusion of the left anterior descending coronary artery. Segment function was determined from pressure-length loop areas inscribed during right ventricular pacing at 128 +/- 3 (mean +/- standard error of the mean) beats/min, and after single closely coupled (179 +/- 3 msec) extrasystoles. Despite a 50 percent decrease in border zone segment function, postextrasystolic potentiation consistently augmented mechanical performance to control levels throughout the ischemic period. Central ischemic zone segment function deteriorated more profoundly, with the development of holosystolic aneurysmal bulging within 30 seconds after occlusion. Nonetheless, postextrasystolic potentiation produced marked inotropic augmentation, but not to control levels, for up to 10 minutes of ischemia. These results suggest that latent viability and contractile reserve may exist during brief periods of coronary occlusion.     

Role of percutaneous transluminal coronary angioplasty in the treatment of unstable angina: Report from the national heart, lung, and blood institute percutaneous transluminal coronary angioplasty and coronary artery surgery study registries

The acute and long-term consequences of PTCA performed in patients with unstable angina was determined in 442 patients with 1-vessel CAD who were enrolled in the NHLBI PTCA Registry. These patients were compared with 214 similar patients in the PTCA Registry with stable angina and with 330 patients with unstable angina from the NHLBI CASS Registry who underwent CABG. The 3 groups had similar baseline characteristics. The immediate angiographic success after PTCA was not different between patients with stable and those with unstable angina. The in-hospital mortality rate was 0.9 % for the PTCA group with unstable angina and 0.47% for the PTCA group with stable angina. The combined 18-month mortality and MI rate was low in both groups (10.8 and 9.5%, respectively). No differences were observed in the mortality and MI rates between patients with unstable angina treated surgically or with PTCA. Both revascularization procedures markedly reduced symptoms of angina. Ninety-two percent of the PTCA group reported improvement in their angina, whereas 80 % of the surgical group had a reduction in angina (p < 0.05). The results from this observational study suggest that PTCA can be performed as safely and successfully in patients with unstable angina as in those with stable angina. PTCA compares favorably with CABG in patients with unstable angina in that the procedure is associated with low mortality and morbidity rates, while marked improvement in symptoms can be expected. Thus, PTCA could be considered an alternative to CABG in patients with unstable angina who have the appropriate anatomic characteristics.     

Preservation of myocardial compliance and reversal of contracture (“Stone heart”) during ischemic arrest by applied intermittent ventricular stretch

The hypothesis was tested that intermittent myocardlal stretch could prevent or reverse the increased stiffness or contracture that occurs during severe ischemia. Isolated rabbit hearts with a fluid-filled left intraventricular balloon underwent 90 minutes of ischemie arrest at 35 °C. In the “no stretch” group (n = 10), the intraventricular balloon remained collapsed during the period of arrest; in the “stretch” group (n = 10) the balloon was expanded every 5 minutes to apply intermittent stretch to the arrested myocardium. Intermittent stretching completely prevented contracture during ischemia. In the no stretch group severe ischemic contracture developed, which increased the pressure in the arrested ventricle to 110 ± 14 mm Hg (mean ± standard error of the mean) after 90 minutes of ischemic arrest; in contrast, no contracture (0 ± 1 mmHg) developed in the stretch group during the period of ischemic arrest (p <0.001 versus the no stretch group). After 60 minutes of reperfusion, the stretch group continued to have less contracture (20 ± 4 mmHg versus 42 ± 7 mmHg, p <0.001). Recovery of contractile function was not impaired by the application of intermittent myocardial stretch. Developed pressure and the first derivative of left ventricular pressure ($\text{dP}\text{dt}$) recovered to a greater extent in the stretch group (38 ± 3 versus 27 ± 5 percent and 54 ± 1 versus 35 ± 7 percent, respectively, in the stretch versus the no stretch group), although these differences were not statistically significant (p = 0.10 to 0.05). Both groups had the same degree of tissue lactate accumulation during the ischemic period and the same levels of tissue edema, adenosine triphosphate and creatine phosphate at the end of the reperfusion period. The results indicate that intermittent myocardial stretch during ischemic arrest can prevent a decrease in diastolic compliance without decreasing recovery of contractile function; the intermittent stretch probably ruptured the rigor or contracture bonds that form during prolonged ischemia.     

Efficacy and safety of incremental doses of diltiazem for the treatment of stable angina pectoris

The safety and efficacy of incremental doses of diltiazem in treating angina pectoris were assessed in 20 patients with functional class II to III exertional angina. During an initial single-blind dose titration phase, dilitiazem produced a dose-related improvement in anginal frequency and exercise capacity. Weekly anginal attacks were reduced to 7.5 +/- 8.9, 5.6 +/- 7.8 and 4.9 +/- 7.3 on diltiazem, 120, 240 and 360 mg per day, respectively, as compared with 11.9 +/- 8.7 on placebo (all p less than 0.001). Treadmill time was significantly enhanced by high dose (360 mg per day) as compared with moderate dose (240 mg per day) diltiazem: 473 +/- 149 versus 424 +/- 146 seconds (p less than 0.05). Time to ischemic ST segment depression was similarly changed: 344 +/- 132 versus 298 +/- 142 seconds (p less than 0.05) by high dose as compared with moderate dose diltiazem. During a subsequent double-blind phase, high dose diltiazem significantly reduced weekly anginal frequency when compared with placebo: 3.1 +/- 3.0 versus 9.3 +/- 7.1 (p less than 0.001); and increased treadmill exercise time: 508 +/- 158 versus 418 +/- 172 seconds on placebo (p less than 0.05). Subjective and objective benefits of high dose diltiazem were sustained during a follow-up period of 6 months without major drug side effects.     

Adverse acute and chronic effects of electrical defibrillation and cardioversion on implanted unipolar cardiac pacing systems

Six cases are presented in which a transient or chronic rise in the stimulation threshold of a permanently implanted unipolar pacemaker resulted in the loss of effective pacing after therapeutic defibrillation or cardioversion. Although damage to the pulse generator may still occur, leading to a loss of function as demonstrated in a seventh patient, improvements in the internal protection circuits of the present generation of pacemakers makes this less likely while possibly predisposing to endocardial burns and increased fibrosis at the electrode-endocardial interface. The theoretical explanations for this phenomenon are discussed, along with recommendations for the prospective and retrospective management of the pacemaker patient who requires defibrillation or cardioversion.     

Electrocardiogram of the athlete: An analysis of 289 professional football players

The electrocardiogram (EGG) of athletes reflects physiologic cardiovascular adaptations that occur in well-conditioned individuals. To more clearly define electrocardiographic changes seen in predominantly power-trained athletes, the ECGs of 289 apparently healthy professional football players were analyzed in detail. The players, aged 21 to 35 years, one-third of whom were black, had a mean body surface area of 2.24 m², a mean heart rate at rest of 56 ± 9 beats/min (with 77% (223) having a rate of less than 60 beats/min), and a mean P axis of 30 ± 25 °. A wide QRS-T angle (>60 °) was present in 14% (41 players) of the group. The mean PR interval was 0.18 ± 0.02 second (>0.21 in 9% [26 players]). Although two-thirds of the players had a QRS duration of 0.10 second, only 1 had right bundle branch block and none had left bundle branch block. The sum of S in lead V₁ plus R in lead V₅ averaged 37 ± 9 mm, with 35% (101 players) demonstrating voltage criteria for left ventricular hypertrophy. The S + R value varied inversely with weight (r = ?0.27, p < 0.002). The maximum T height in any lead had a mean of 8.6 ± 3 mm, with 22% (64 players) having a T height ≥11 mm. U waves were universally present. ST-T changes mimicking ischemia were noted in 39 of 289 players (13%), 22 (58%) of whom were black (p < 0.001). The maximal J-point elevation in any lead averaged 1.9 ± 0.9 mm. These findings confirm that the ECGs of power-trained athletes show changes similar to those of endurance-trained athletes. These changes most likely reflect the increased vagal tone and ventricular mass observed in conditioned athletes. Large body size masks the voltage changes expected with increased left ventricular mass. Ischemic-like ST-T-wave deviations were found predominantly in black athletes.     

Efficacy and safety of verapamil in patients with angina pectoris after 1 year of continuous,high-dose therapy

The long-term efficacy and safety of high-dose verapamil therapy (480 mg/day) was assessed in 26 patients with chronic stable angina pectoris during a 3-phase protocol: Phase 1—an initial, 6-week placebo-controlled, double-blind crossover assessment; Phase 2—an open label, 1-year follow-up; and Phase 3—a final drug withdrawal and rechallenge 10-week study. Three patients withdrew during Phase 2(1 had hepatitis and 2 underwent coronary bypass surgery). Adverse effects during Phase 2 were mild, consisting of constipation (6 patients) and prolongation of the P-R interval (5 patients); however, no patient required alteration of the 480 mg/day dosage. At the end of Phase 2, 10 patients underwent the Phase 3 study, commencing with a 2-week period in which verapamil was either tapered gradually or abruptly discontinued. This was followed by an 8-week double-blind, placebo-controlled crossover rechallenge study with verapamil. The clinical and exercise responses to verapamil compared with placebo were similar during the Phase 3 protocol and the initial Phase 1 study (treadmill time increased by 55% and anginal attacks per week decreased by 63% during Phase 3, compared with a 28% increase and a 42% decrease, respectively, during Phase 1, p = not significant [NS]). Withdrawal of verapamil produced a similar return of anginal symptoms whether the drug was abruptly discontinued or its administration tapered. No patient had unstable angina pectoris or acute myocardial infarction.These investigations demonstrate that verapamil is safe and effective when evaluated after 1 year of continuous therapy using a dosage of 480 mg/day. There is no evidence of drug tachyphylaxis, nor does verapamil appear to cause an abrupt withdrawal syndrome in patients with chronic stable angina pectoris.     

Cardiokymography during exercise testing: A new device for the detection of coronary artery disease and left ventricular wall motion abnormalities

The cardiokymograph (CKG) is a device that has been shown to reflect left ventricular (LV) wall motion abnormalities. Its accuracy in detecting coronary artery disease (CAD) during treadmill exercise testing was assessed in 204 consecutive patients undergoing coronary arteriography. Of the 188 patients with a technically adequate CKG, 146 (78%) had significant CAD. The sensitivity and specificity were similar for both the exercise electrocardiogram (ECG) (66% and 86%, respectively) and the exercise CKG (73% and 95%, respectively). An abnormal exercise CKG was significantly more common In patients with 3-vessel CAD than in those with 1-vessel disease (97% versus 52%, respectively;p < 0.001) and in patients with left anterior descending disease than in those without (85% versus 26%, respectively; p < 0.001). Seventy patients showed both an abnormal exercise ECG and CKG; all had CAD and 86% had multivessel CAD. Forty-eight patients demonstrated a normal exercise ECG and CKG; 29% had CAD but only 6% had multivessel CAD. Among 55 patients who had simultaneous exercise radionuclide ventriculography, new septal or apical wall motion abnormalities were found in 79% (23 of 29) of patients with an abnormal CKG compared with 19% (5 of 26) of patients with a normal CKG (p < 0.001). Thus, the CKG during exercise testing accurately reflects LV wall motion abnormalities and can be used to improve the diagnostic accuracy of exercise testing as an additional marker of myocardial ischemia.     

Role of hypertension in atherosclerosis and cardiovascular disease.

Clinical, experimental and pathologic studies strongly indicate that hypertension is a major factor in coronary heart disease, sudden death, stroke congestive heart failure and renal insufficiency. The deleterious effect of the elevated blood pressure on the cardiovascular system appears to be due mainly to the mechanical stress placed on the heart and blood vessels. Humoral factors and vasoactive hormones such as angiotensin, catecholamines and prostaglandins may play a role in the pathogenesis of hypertensive cardiovascular disease but this role has not yet been defined and is probably secondary. Hypertension and the resulting increase in tangential tension on the myocardial and arterial walls, leads to the development of hypertensive heart disease and congestive heart failure as well as hypertensive vascular disease that affects not only the kidneys but also the heart and brain. Hypertensive vascular disease involves both large and small arteries as well as arterioles and is characterized by fibromuscular thickening of the intima and media with luminal narrowing of the small arteries and arterioles. The physical stress of hypertension on the arterial wall also results in the aggravation and acceleration of atherosclerosis, particularly of the coronary and cerebral vessels. Moreover, hypertension appears to increase the susceptibility of the small and large arteries to atherosclerosis. Thus the patient with hypertension is a candidate for both hypertensive and atherosclerotic vascular disease of the coronary and cerebral vessels leading to occlusive disease of both the large and small arteries and resulting in myocardial infarction and stroke. Other major complications of hypertensive vascular disease include rupture and thrombotic occlusion of blood vessels, especially in the brain. Disease of the arterial media, which begins in childhood with the deposition of calcium in the vessels, may be an important cause of arterial hypertension. This form of hypertension may manifest itself in adults as arteriosclerotic hypertension and lead to cardiovascular complications very similar to those of essential hypertension. The relation of arteriosclerotic hypertension to nutritional factors, including dietary salt intake, deserves study.     

Effect of antiplatelet therapy on restenosis after experimental angioplasty

Restenosis is recognized as a common complication of PTCA and can limit the long-term benefit of this procedure. To study the effect of antiplatelet agents in preventing restenosis, 25 New Zealand rabbits had bilateral iliac stenoses created by balloon deendothelialization and a 2% cholesterol diet for 6 weeks. After angiographic delineation of the iliac atherosclerosis, successful angioplasty was performed in all rabbits, with an average increase in luminal diameter of 0.9 mm (81%). Seven rabbits received aspirin (32 mg/day) plus dipyridamole (25 mg/day) and 9 received sulfinpyrazone (100 mg/ day); 9 were given no antiplatelet drugs and served as controls. After 4 weeks of drug therapy and a continued atherogenic diet, angiography was repeated and the rabbits were killed for histologic examination. The angiographic luminal diameter was similar for these groups both before and immediately after angioplasty. However, the luminal diameter 4 weeks later was significantly larger in both the aspirin plus dipyridamole and the sulfin-pyrazone groups compared with the control rabbits (1.3 ± 0.6 and 1.8 ± 0.5 mm vs 0.7 ± 0.6 mm, respectively, p < 0.05). Histologic examination revealed intraluminal clot in 4 of 9 control rabbits and in none of the drug-treated rabbits. Also, less intimal thickening was evident. In conclusion, aspirin plus dipyridamole and sulfinpyrazone inhibited angiographic restenosis after transluminal angioplasty in this experimental model. These findings support the use of antiplatelet agents in clinical angioplasty and suggest that platelet aggregation at the angioplasty site may promote restenosis.     

Prognostic importance of a clinical profile and exercise test in medically treated patients with coronary artery disease

To identify predictors of mortality in medically treated patients with symptomatic coronary artery disease, 30 variables were analyzed in 4,083 patients. Regression analysis demonstrated that seven variables were independent predictors of survival. A high risk subgroup (annual mortality rate above 5%) was identified, consisting of patients with either a congestive heart failure score of 3 to 4 or 1 mm or greater ST segment depression and final exercise stage of 1 or less. When all 30 variables were analyzed conjointly, the left ventricular contraction pattern (p less than 0.0001) and the number of diseased coronary vessels (p less than 0.003) proved to be the most important predictors of survival. In a subgroup of 572 patients with three vessel coronary disease and preserved left ventricular function, the probability of survival at 4 years ranged from 53% for patients only able to achieve stage 1/2 of exercise to 100% for patients able to exercise into stage 5 (p less than 0.004). Thus, in patients with defined coronary pathoanatomy, clinical and exercise variables primarily relating to the functional state of the left ventricle are helpful in assessing prognosis.     

Prognostic significance of angiographically documented left ventricular aneurysm from the Coronary Artery Surgery Study (CASS)

In order to evaluate the prognosis of medically treated patients with angiographically defined left ventricular aneurysm the data available from 1,136 patients with aneurysm (7.6 percent) from 15,019 patients with coronary artery disease in the Coronary Artery Surgery Study (CASS) registry were analyzed. Prior myocardial infarction, reduced ejection fraction, absence of angina and evidence of congestive heart failure were more commonly present in patients with aneurysm. The cumulative survival rates of medically treated patients at 1, 2, 3 and 4 years were 90, 84, 79 and 71 percent, respectively. The Cox analysis of survival indicated that the following variables predicted outcome: age, residual left ventricular function as assessed with angiography, left ventricular end-diastolic pressure, functional impairment due to congestive heart failure, number of vessels diseased, mitral regurgitation and S₃ gallop. When survival was stratified for similar degrees of left ventricular dysfunction and functional impairment there was no difference between the survival of patients with aneurysm and that of registry patients without aneurysm.The data from this large population study indicate that the survival of patients with left ventricular aneurysm is better than previously recognized. The mortality in this group is primarily related to age, left ventricular function and clinical severity of heart failure. The presence of an aneurysm does not independently alter survival.     

Verapamil therapy for stable exertional angina pectoris

Clinical and exercise responses to therapy with the calcium-channel blocking agent verapamil were assessed in 26 patients with stable exertional angina pectoris using a double-blind, placebo-controlled, randomized crossover study design. Verapamil, 480 mg daily, reduced the frequency of angina attacks (5.6 +/- 7.3 to 2.2 +/- 3.0 attacks per week, p less than 0.001) and number of nitroglycerin tablets consumed (3.4 +/- 4.9 to 1.2 +/- 2.5 tablets per week, p less than 0.05), and increased exercise duration (6.4 +/- 2.1 to 7.5 to 1.8 minutes, p less than 0.001) (all data are mean +/- standard deviation). These changes were significantly better than those seen with placebo. These beneficial effects of verapamil were related to significant reduction in the heart rate-systolic blood pressure product during submaximal exercise. Adverse effects from verapamil were few and consisted primarily of constipation in 6 patients. A total of 193 patients had been entered in 6 independent clinical trials, which have compared verapamil with placebo for the treatment of stable exertional angina pectoris, using a similar study design. The combined evidence from all these studies indicates that verapamil is a highly effective and safe drug for the treatment of stable effort-related angina pectoris.     

Decrease in systolic blood pressure during exercise testing: Reproducibility,response to coronary bypass surgery and prognostic significance

To investigate the reproduclbility and prognostic significance of an exercise-induced decrease in systolic blood pressure, 47 patients were Identified who manifested such a reduction below the pre-exercise standing level in a consecutive series of 436 patients who underwent treadmill exercise testing and cardiac catheterization during a 3 year period. The prevalence of this abnormal finding was 11 percent in the total group but 21 percent in the 124 patients with three vessel or left main coronary artery disease. Patients with an exercise-Induced reduction in systolic blood pressure were more likely to be male, have typical angina pectoris with class III or IV functional limitation and to have had a prior myocardial infarction than were patients without this finding (p < 0.05). Although no complications occurred during the exercise test of these 47 patients, the majority had severe ischemic responses, and 14 (30 percent) showed complex repetitive ventricular arrhythmias. Of the 47 patients, 24 (group 1a) received medical treatment and 23 (group 1b) underwent coronary bypass surgery. On repeat exercise testing In 42 patients, a decrease in systolic blood pressure during exercise was consistently present in group 1a (17 of 20) but entirely absent (0 of 22) in group 1b (p < 0.001). The mean treadmill time, peak heart rate and systolic blood pressure were not significantly different in the initial and on repeat exercise tests in patients in group 1a; however, in patients in group 1b, all of these variables were significantly higher in the repeat test (p < 0.001). At a mean follow-up time of 37 months, the total cardiac mortality rate was 8 percent (2 of 24) in group 1a and 4 percent (1 of 23) in group 1b. It is concluded that a decrease in systolic blood pressure during exercise testing is highly reproducible and appears to be reversed by coronary bypass surgery.     

Derivation of systolic time intervals from doppler measurement of temporal arterial blood flow

The carotid pulse method of recording systolic time intervals is limited by significant motion-induced artifact, making it unsuitable for studying patients during exercise. As an approach to overcoming this limitation, a new method utilizing the blood velocity profile of the superficial temporal artery measured by Doppler ultrasound has been developed. When compared with the values obtained from the conventional carotid pulse method, Doppler-derived left ventricular election time and preejection period showed excellent correlation (r = 0.99 for both) and the Doppler-derived measurements showed little intra- or interobserver variability. Studies performed during treadmill exercise showed that in 8 of 10 subjects, suitable tracings could be recorded through stage 3 of the Bruce protocol, confirming the enhanced stability of the technique compared with the carotid pulse method.     

Ventricular arrhythmias during exercise testing: mechanism, response to coronary bypass surgery and prognostic significance

To investigate the determinants and prognostic significance of ventricular arrhythmias during exercise testing, 86 patients with such arrhythmias were identified from a consecutive series of 446 patients who underwent treadmill exercise testing and cardiac catheterization. The prevalence of these arrhythmias was 19% in the total group but increased to 30% in the 120 patients with 3-vessel or left main coronary artery disease. Patients with exercise-induced arrhythmias were more likely to have 3-vessel or left main coronary artery disease, a lower resting ejection fraction, greater than or equal to 2 mm of ischemic ST depression and more severe segmental wall motion abnormalities than patients without this finding (p less than 0.05). Repeat exercise testing in 22 patients with exercise-induced arrhythmias after coronary bypass surgery revealed that persistence of these arrhythmias was associated with either severe wall motion abnormalities preoperatively or residual ischemic ST depression during the post-operative exercise testing. At a mean follow-up period of 5.3 years, the presence of exercise-induced ventricular arrhythmias was not associated with increased cardiac mortality in the medically treated patients.     

Primary (AL) amyloidosis as a cause of breast masses

Amyloidosis is rarely considered in the differential diagnosis of breast masses. During the past six years, 27 women with primary (24) and multiple myeloma-associated (three) amyloidosis (AL amyloid) were evaluated at our center. In five of these patients, amyloid was demonstrated on microscopic examination of breast tissue. The clinical presentations were similar to fibrocystic breast disease in two cases and malignancy in two others. Amyloidosis of the breast may be more common than previously recognized, especially considering the predilection of amyloid for depositing around fat cells. Therefore, pathologic examination of nonmalignant breast tissue should include Congo red staining and viewing under polarized light.     

Anatomic and physiologic considerations of a cardiogenic hypertensive chemoreflex.

Within both human and canine hearts there is a mass of chemoreceptor tissue lying just between the origins of the aorta and pulmonary artery and receiving its blood supply from the proximal portion of the left coronary artery. In the dog this is considered to be the site of origin for a powerful hypertensive reflex stimulated by serotonin. There is brief generalized arterial vasoconstriction, except for the coronary and pulmonary arteries. The afferent limb of this cardiogenic hypertensive Chemoreflex courses in thoracic branches of the vagus. Autonomic efferent responses are both vagal arid, sympathetic events. These include simultaneous positive and negative inotropic effects on the atria, a positive inotropic effect on both ventricles, positive and negative chronotropic actions and similarly mixed dromotropic effects. Methods for separately identifying and quantifying these responses are discussed and illustrated. Vagotomy eliminates the reflex, as does the administration of cyproheptadine (but not methysergide). Among possible human counterparts for this cardiogenic hypertensive Chemoreflex are the pressor responses associated with angina pectoris, with very early acute myocardial infarction and after certain forms of cardiac surgery such as saphenous vein bypass grafting.