Gregory D. Curfman

Sustained Effectiveness of Converting-Enzyme Inhibition in Patients with Severe Congestive Heart Failure

Eight patients with severe congestive heart failure refractory to conventional therapy, including vasodilators, were given captopril (seven patients) or teprotide (one patient). All had dyspnea, edema, elevated pulmonary wedge pressure (28.0 +/- 2.6 mm Hg), low cardiac index (1.6 +/- 0.1 liters per minute per square meter), and elevated levels of serum creatinine (2.3 +/- 0.2 mg per deciliter [203.3 +/- 17.7 mumol per liter]), blood urea nitrogen (48 +/- 5 mg per deciliter [17.1 +/- 1.8 mmol of urea per liter]), plasma renin activity (21 +/- 7 ng of angiotensin I per milliliter per hour), plasma angiotensin II (271 +/- 51 pg per milliliter), and plasma aldosterone (65 +/- 14 ng per deciliter). After one week of therapy, all indexes improved. Creatinine and p-aminohippurate clearances were also increased (P less than 0.01). Improvement was sustained (more than six months) and was associated with a statistically significant increase in the cardiac ejection fraction (12 +/- 3 to 26 +/- 7 per cent). With a mean follow-up of seven months, the New York Heart Association Functional Class has been reduced from IV to II, and the number of days of hospitalization to less than 10 per cent of that before captopril therapy. We conclude that captopril reduces afterload in advanced congestive heart failure and induces sustained improvements in clinical status and renal function.

Medical Devices — Balancing Regulation and Innovation

The FDA approval system cannot assure the safety and effectiveness of increasingly complex medical devices. The Institute of Medicine has recommended eliminating a process that permits approval of a device based on its “substantial equivalence” to an existing device.

Intravenous nitroglycerin in the treatment of spontaneous angina pectoris: a prospective, randomized trial.

A prospective, randomized study of i.v. nitroglycerin (TNG) in the management of repetitive spontaneous angina pectoris was undertaken in 40 consecutive patients. The clinical effectiveness of i.v. TNG (group A) was compared with that of oral isosorbide dinitrate (ISDN) and topical 2% nitroglycerin ointment (NO) in combination (group B) during a 72-hour treatment period. The doses of both nitrate regimens were adjusted so that the mean arterial pressure in the two groups was reduced by 15 ± 3% of control values to the same level (77 mm Hg). The i.v. TNG dose of 10–200, gg/min yielded arterial plasma TNG levels of 1.2–65.3 ng/m] and estimated plasma (arterial) clearance of 106 ± 55 ml/min/kg of body weight (mean ± SD). In group B, the doses were 20–60 mg (oral ISDN) and 1/2-2 inches (NO) every 6 hours. Intravenous TNG reduced the number of spontaneous ischemic episodes from 3.3 ± 0.8 per 24 hours during the control period to 1.0 ± 0.3 per 24 hours during the treatment period (p < 0.01), while the ISDN/NO combination reduced the number of episodes from 3.1 ± 0.4 to 1.4 ± 0.3 (p < 0.01). Overall, the magnitude of the therapeutic effect of i.v. TNG was statistically indistinguishable from that of ISDN/NO, although i.v. TNG did have somewhat greater clinical benefit on day 2 of the 3-day treatment period. Furthermore, the data suggested more consistent control of ischemic episodes with i.v. TNG during the first 24 hours of the trial. Although both regimens markedly reduced the frequency of spontaneous ischemic episodes, only 36% of patients in group A and 17% in group B experienced no ischemic episodes during the study period (NS). Forty-three percent of patients in group A and 61% in group B (NS) required early coronary artery bypass surgery to control recurrent ischemic episodes refractory to medical therapy. We conclude that i.v. TNG and ISDN/NO, when administered in doses adjusted to produce similar effects on systemic arterial pressure, have nearly equivalent clinical effects in the management of patients with frequent episodes of spontaneous angina pectoris. Intravenous TNG offers the advantage of more consistent control of ischemic episodes during the first 24 hours of treatment. Nevertheless, the recurrence rate of spontaneous ischemic episodes during medical therapy is high with both regimens, and early coronary artery bypass surgery may be required for long-term management.

Oral amrinone in refractory congestive heart failure

The acute effects of an oral preparation of amrinone, a recently synthesized cardiotonic agent, were assessed noninvasively in nine patients who had advanced heart failure that persisted despite treatment with digitalis, diuretic drugs and afterload-reducing agents. All patients demonstrated an improvement in left ventricular ejection fraction determined by radionuclide ventriculography (20.3 +/- 2.8 to 30.8 +/- 4.8 percent [mean +/- standard error of the mean], p less than 0.005) after a single dose of amrinone. Initial effects were seen within 1 hour, with the peak effect occurring at 1 to 3 hours; persistent effects were demonstrable at 4 to 6 hours. No change in blood pressure, heart rate or rhythm was observed, and there was no clinical evidence of myocardial ischemia. Continued benefit was demonstrated by radionuclide ventriculography in two patients treated for 1 and 6 weeks, respectively, although two other patients experienced major side effects with the chronic administration of amrinone. Although orally administered amrinone shows promise as a potentially useful agent in the treatment of advanced heart failure, the safety of this drug remains to be established.

Is Exercise Beneficial -- or Hazardous -- to Your Heart?

At one time or another, most physicians have encountered a patient -- perhaps even a friend or family member -- who suffered a heart attack during strenuous physical exertion. Some familiar example...

Why Doctors Should Worry about Preemption

A leading drug company may be poised to win a landmark legal victory next fall. Dr. Gregory Curfman, Stephen Morrissey, and Dr. Jeffrey Drazen write that if Wyeth prevails in a case soon to be argued before the U.S. Supreme Court (Wyeth v. Levine), drug companies could effectively be immunized against state-level tort litigation if their FDA-approved products are later found to be defective.

Thyroid-induced alterations in myocardial sodium-potassium-activated adenosine triphosphatase, monovalent cation active transport, and cardiac glycoside binding.

The effects of thyroid hormone on guinea pig myocardial NaK-ATPase activity, transmembrane monovalent cation active transport, and cardiac glycoside binding were were examined. NaK-ATPase activities of left atrial and left ventricular homogenates of control and triiodothyronine (T3)-treated animals were determined, and compared to activities of skeletal muscle and liver. T3 administration was associated with a significant increase of 18% in left atrial and left ventricular NaK-ATPase specific activities. This increment was less than that noted in skeletal muscle (+42%) and liver (+30%). To determine if enhanced NaK-ATPase activity was accompanied by increased monovalent cation active transport, in vitro 86Rb+ uptake by left atrial strips and hemidiaphragms was measured. Transition from the euthyroid to the hyperthyroid state resulted in a 68% increase in active 86Rb+ uptake by left atrium, and a 62% increase in active uptake by diaphragm. Passive 86Rb+ uptake was not affected in either tissue. Ouabain binding by atrial and ventricular homogenates of T3-treated animals was increased by 19 and 17%, respectively, compared to controls, in close agreement with thyroid-induced increments in NaK-ATPase activiey. Taken together, these results are consistent with enhanced myocardial NaK-ATPase activity and monovalent cation activt transport due to an increase in the number of functional enzyme complexes.

The Health Benefits of Exercise -- A Critical Reappraisal

In his 1772 account of angina pectoris, the English physician William Heberden described a patient who “set himself a task of sawing wood for half an hour every day, and was nearly cured”1. More re...

A pragmatic view of the new cholesterol treatment guidelines.

On November 12, 2013, updated guidelines for the treatment of high blood cholesterol levels were released by the American College of Cardiology– American Heart Association (ACC-AHA) Task Force on Practice Guidelines.1 This update represents the first major guideline revision since the National Cholesterol Education Program released its Adult Treatment Panel III report in 2002.2 The previous guidelines were widely accepted and applied with relative consistency. In contrast, the new guidelines have already been the subject of controversy, with some observers arguing that some elements of the recommendations are not evidence-based.3 Nevertheless, these recommendations may have a major effect on the clinical practice of lipid management. We therefore provide here a brief practical summary of the current cholesterol guidelines, indicating the area of dispute.

Valve replacement for aortic regurgitation: long-term follow-up with factors influencing the results.

One hundred consecutive cases of valve replacement for aortic regurgitation performed between 1967–1971 were analyzed to identify and quantitate factors related to a favorable result. Of 83 perioperative survivors, 78% (n = 65) became asymptomatic and 58% (n = 48) were alive 5–9 years postoperatively. The cause of aortic regurgitation affected both the speed of progression of symptoms and the postoperative result.Death due to myocardial failure may be prevented by optimal timing of operation. Accordingly, we identified variables that discriminated between patients who had an excellent postoperative result and those who died of myocardial failure. The most important discriminators were the severity (p = 0.03) and duration (p = 0.04) of dyspnea, the extent of therapy for heart failure (p = 0.001), physical findings of left ventricular failure (p = 0.002), the cardiothoracic ratio (p = 0.007), the resting pulmonary capillary wedge pressure (p = 0.01), and a cardiac index < 2.2 I/min/m2 (p = 0.03).The data suggest that evidence of left ventricular failure, even of mild degree, is an indication for operation in patients with severe aortic regurgitation