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Angiotensin II modulates beat-to-beat cardiac performance as a potent vasocontrictor, inotrope, and regulator of water and electrolyte balance. It is also a growth factor that can stimulate the early molecular growth responses of proto-oncogene activation and new protein synthesis, and the later event of cardiocyte hypertrophy independent from load. Its effects are mediated through the angiotensin II type 1 (AT1) receptor, which exists as the AT1a and AT1b isoforms, and the angiotensin II type 2 (AT2) receptor. There is still controversy regarding the role of activation of the AT1 receptor subtype(s) as a mandatory signal versus modulatory regulator of the transduction of mechanical load in pressure-overload hypertrophy due to hypertension or aortic stenosis. The role of the AT2 receptor subtype in the heart is even less well understood, although this receptor appears to serve as an antigrowth signal in proliferating cells. Here we review current data on these controversies, including new data that support the notion that angiotensin II activation of the cardiac AT2 receptor subtype inhibits the effects of angiotensin II on the immediate growth response in the adult heart.

A 27 year old woman was hospitalized for progressive dyspnea, fatigue and retrosternal chest pain. She had progressive cardiac enlargement with clinical and laboratory confirmation of a dilated cardiomyopathy. Transvenous percutaneous right ventricular endomyocardial biopsy yielded a specimen showing a noncaseating granuloma. The patient's dyspnea responded dramatically to steroid therapy with corresponding improvement in radiographic and echographic measures of ventricular performance. This case illustrates the problem of diagnosing cardiac sarcoidosis when there is no apparent evidence of other organ involvement.

Recent studies in patients with either obstructive or nonobstructive hypertrophic cardiomyopathy have suggested that increased resistance to diastolic filling of the stiff left ventricle may be an important mechanism contributing to symptoms. These observations have led to exploration of the effects of calcium channel blockers on systolic and diastolic function in patients with hypertrophic cardiomyopathy. Acute hemodynamic studies using verapamil and nifedipine have shown that these agents tend to cause: (1) a slight fall in systemic arterial pressure and reflex increase in heart rate; (2) a reduction in left ventricular outflow gradient in most but not all patients; and (3) variable effect on left-side heart filling pressures. In contrast to beta-adrenergic blockers, these hemodynamic effects are not associated with depression of systolic function, but appear to be related to improved left ventricular distensibility. Clinical trials have suggested that long-term administration of verapamil in patients with hypertrophic cardiomyopathy promotes improvement in symptomatic status and exercise tolerance in many but not all patients; similar results have been reported in preliminary studies using nifedipine. Potential major adverse effects include depression of sinoatrial activity and atrioventricular conduction with verapamil, and marked hypotension and, rarely, pulmonary edema with both verapamil and nifedipine.

The calcium blocking agent nifedipine was shown to protect the isolated left ventricle against the development of altered diastolic compliance during severe global ischemia. To assess the influence of nifedipine during myocardial ischemia in human subjects, we studied the effect of nifedipine (20 mg sublingually) on the hemodynamic response to pacing tachycardia (heart rate 66 +/- 4 to 143 +/- 4 beats per minute) in 17 patients with multivessel coronary artery disease. Typical anginal pain occurred in all patients during pacing tachycardia before nifedipine, but in only 3 of 17 patients during pacing after nifedipine. In 11 patients a significant (greater than or equal to 5 mm Hg) increase in postpacing left ventricular end-diastolic pressure (LVEDP, 15 +/- 2 mm Hg to 28 +/- 2 mm Hg, p less than 0.01) developed, and was associated with an upward shift of the left ventricular diastolic pressure-volume curve. In these patients, pretreatment with nifedipine did not alter resting LVEDP or aortic pressure, but did attenuate or abolish the increase n LVEDP and the shift in left ventricular diastolic pressure-volume curves after pacing tachycardia to the same rate and for the same duration. The antianginal effect of nifedipine was not associated with a reduction in contractility, because there was no change in LV + dp/dt after nifedipine. However, the increase in left ventricular systolic pressure achieved in response to pacing tachycardia was less after nifedipine. We conclude that nifedipine favorably modifies the symptomatic and hemodynamic response to pacing tachycardia in patients with coronary artery disease. The mechanism is uncertain and could involve a direct myocardial effect, peripheral vasodilation, coronary vasodilation or a combination of these effects.

Although it has been suggested that calcium channel blocking agents may be utilized as vasodilators in patients with congestive heart failure, these agents also have the potential to cause a deterioration in cardiac function because of their negative inotropic actions. There is considerable variation among the available agents with regard to their relative effects on the vasculature, myocardial inotropy, and myocardial chronotropy. Thus, at clinically relevant dosages, nifedipine is a potent systemic and coronary vasodilator, but it has little or no direct effect on inotropy and chronotropy. In contrast, verapamil exerts significant negative inotropic and chronotropic effects at vasodilatory dosages, whereas diltiazem is a potent vasodilator with a negative chronotropic action at dosages that do not affect inotropy. In patients with heart failure, the largest experience so far has been with nifedipine. Data derived from over 100 patients with moderate to severe congestive heart failure indicate a generally beneficial net hemodynamic response to nifedipine, with substantial improvements in cardiac index (+24 percent) and left ventricular filling pressure (-15 percent). The major effect seems to be on arteriolar resistance vessels, resulting in a reduction in afterload, with relatively little effect on venous pressures. Limited data suggest that the initial effect is sustained during long-term therapy. The clinical experience with verapamil and diltiazem in patients with heart failure is at present limited. In patients with normal or mildly impaired left ventricular function, verapamil's vasodilator and negative inotropic effects are counterbalanced. With severe left ventricular dysfunction, however, treatment with verapamil can result in abrupt decompensation and development of overt pulmonary edema and hypotension. Diltiazem's relative lack of negative inotropic effects may allow it to be used safely in patients with congestive heart failure, particularly when control of supraventricular tachyarrhythmia is required.

Pulsus paradoxus is a key physical finding in patients with cardiac tamponade. This report describes a 38-year-old woman with metastatic adenocarcinoma who had cardiac tamponade confirmed by cardiac catheterization. Pulsus paradoxus was notably absent. No evidence could be found for an atrial septal defect, significant aortic regurgitation, elevated left ventricular diastolic pressure, or localized tamponade, previously described disorders in which pulsus paradoxus may not be seen when tamponade occurs. The lack of pulsus paradoxus in this case was attributed to right ventricular pressure overload due to mechanical obstruction of the pulmonary artery.

To evaluate current strategies for the management of unstable angina, 104 consecutive patients admitted to the coronary care unit with unstable angina during a 6-month period were followed prospectively. Although 58 patients had symptomatic relief with the initiation of intensive medical therapy, 46 (44%) continued to have episodes of angina despite maximal tolerated triple-drug antianginal therapy as well as aspirin or heparin, or both. In-hospital mortality for the 104 patients was 4%. The incidence of myocardial infarction was 8%, and differed (p less than 0.01) for the medically responsive group (3%) vs the medically refractory group (13%). Based on clinical status and coronary anatomy, patients were referred for either bypass surgery (46%), coronary angioplasty (41%) or continued medical therapy (13%). Choice of therapy varied according to the extent of coronary disease, with coronary angioplasty attempted in 72% of patients with 1-vessel disease, 44% of patients with 2-vessel disease and 7% of patients with 3-vessel disease. Angioplasty was performed with an initial success rate of 88%, and compared favorably with bypass surgery in terms of in-hospital mortality (0 vs 11%), late mortality (2.8 vs 7.7%), freedom from angina (62 vs 69%) and subsequent employment (44 vs 27%) at 18 months follow-up. The favorable results of angioplasty in this prospective observational study suggest that additional randomized trials should be conducted in this important patient group.

Twelve patients with a clinical diagnosis of right ventricular infarction are described. All had acute inferior wall myocardial infarction associated with the bedside findings of jugular venous distension, clear lungs on auscultation, and arterial hypotension. Hemodynamically, there was elevation of right-sided filling pressures not explained by normal or minimally elevated pulmonary wedge pressures. Four patients had an incorrect diagnosis of acute cardiac tamponade. However, a review of the data showed that the hemodynamic features of right ventricular infarction more closely resemble those of pericardial constriction, a point that may be helpful in distinguishing right ventricular infarction from cardiac tamponade. Invasive and noninvasive techniques that exclude the presence of pericardial fluid and suggest enlargement and abnormal contractility of the right ventricle were helpful in establishing the diagnosis of right ventricular infarction in several patients.

Without revascularization, patients with non-Q-wave acute myocardial infarction (AMI) are predisposed to angina, recurrent AMI and cardiac death. Percutaneous transluminal coronary angioplasty (PTCA) was performed in 68 patients with angina an average of 2.3 months after non-Q-wave AMI (41 anterior, 27 inferior). Mean diameter stenosis was 95%, with collateralized total occlusion of the infarct-related artery in 23 patients. PTCA was successful in 87% (59 of 68), with a mean residual stenosis of 30%. One patient had emergency bypass surgery. Long-term follow-up (average 17 +/- 10 months) was available for 58 of the 59 patients in whom PTCA was successful. Recurrent angina developed in 41% (24 of 58), but was relieved by repeat PTCA in 14, by late coronary artery bypass surgery in 4 and by medical therapy in 6. There was 1 nonfatal AMI, due to progressive disease in a nondilated vessel, and 1 noncardiac death At last follow-up, 46 of 58 patients (79%) were asymptomatic and fully active or employed. Thus, patients undergoing PTCA for angina after non-Q-wave AMI appear to have a relatively high clinical restenosis rate, but with repeat PTCA have a low incidence of subsequent angina, AMI and cardiac death.