Beneficial effects of pimobendan on exercise tolerance and quality of life in patients with heart failure. Results of a multicenter trial. The Pimobendan Multicenter Research Group.

BACKGROUND: This multicenter trial was conducted to determine the efficacy and safety of pimobendan, an inotropic agent with calcium-sensitizing properties and activity as a phosphodiesterase inhibitor, in patients with heart failure. METHODS AND RESULTS: One hundred ninety-eight ambulatory patients with symptoms of moderate to severe heart failure despite therapy with digitalis and diuretics with or without a single vasodilator were randomly assigned to receive either placebo (n = 49) or pimobendan (n = 149) in a double-blind fashion for 12 weeks. A dose range of pimobendan was used including 2.5 (n = 49), 5 (n = 51), or 10 mg/day (n = 49). One hundred fifty-eight (80%) patients were taking a converting enzyme inhibitor (CEI) and 28 (14%) patients were taking a non-CEI vasodilator. At end point, the 5-mg dose of pimobendan significantly increase exercise duration compared with placebo (121.6 +/- 19.1 seconds, p less than 0.001), whereas the 10-mg dose produced an increase of borderline significance (81.1 +/- 19.5 seconds, p = 0.05). Peak VO2 was significantly increased by 2.23 +/- 0.58 ml/kg/min in the 5-mg group (p less than 0.01 versus placebo). Furthermore, quality of life measured with the Minnesota Living With Heart Failure Questionnaire improved by 8.5 +/- 2.3 units in the 5-mg group compared with 1.3 +/- 2.2 units in the placebo group (p less than 0.01). There were a total of 23 all-cause hospitalizations in the placebo group, which was significantly greater compared with 33 in the three groups treated with pimobendan (p less than 0.01). There were no significant differences between the placebo and pimobendan groups with respect to changes in ejection fraction and plasma norepinephrine measured at baseline and at the completion of the 12-week study, proarrhythmic effect, or the number of patients with a significant adjustment in background therapy. Eleven patients died, including three (6%) on placebo and eight (5%) on pimobendan (p = NS). Among all adverse events, headache tended to be more common in the pimobendan groups compared with placebo, with the incidence increasing with dose (p less than 0.05). CONCLUSIONS: These data demonstrate that pimobendan significantly increases exercise duration, peak VO2, and quality of life in patients with heart failure. Pimobendan appears to be useful adjunctive therapy when added to digitalis, diuretics, and vasodilators.

Efficacy and safety of a short-term (6-h) intravenous infusion of dopexamine in patients with severe congestive heart failure: a randomized, double-blind, parallel, placebo-controlled multicenter study.

Dopexamine hydrochloride is a new synthetic catechol that offers a unique profile of adrenergic and dopaminergic activity. In this multicenter, parallel design, placebo-controlled study, 45 patients with functional class III or IV chronic congestive heart failure were randomized to receive a placebo infusion or one of three different doses of dopexamine. After a 2-h dose titration sequence, patients received a 6-h constant dose infusion. During this 6-h period, dopexamine was infused at rates of 1, 2 and 4 micrograms/kg body weight per min in the low, intermediate and high dose groups, respectively. In patients receiving high dose infusion, dopexamine produced a 78% increase in cardiac index associated with a 43% decrease in systemic vascular resistance and 24% increase in heart rate (p less than 0.05 vs. placebo for all three variables). There was a trend (p = NS) toward a moderate increase in cardiac index at low and intermediate doses. In patients randomized to receive dopexamine, right atrial, systemic arterial, pulmonary artery and pulmonary capillary wedge pressures showed minimal change from baseline and did not differ statistically from the placebo response. Very few patients developed adverse reactions related to dopexamine, although five patients randomized to receive high dose and three patients randomized to receive intermediate dose dopexamine required dose reduction because hemodynamic variables exceeded arbitrary safety limits or the patients developed symptoms related to the study medication. dopexamine in higher doses effectively increases cardiac index in association with a reduction in systemic vascular resistance. Additional clinical studies are indicated to evaluate the merits of dopexamine in comparison with other inotropic and vasodilator medications.

Modern trends in the management of heart failure.

An increasing number of medications are available to the physician treating heart failure. Initial therapy involves diuretics, with digitalis, vasodilators, and anticoagulants used for progressive disease. Additional medications such as the phosphodiesterase inhibitors offer promise for the future. In selected patients, the results of heart transplantation have been extremely gratifying and frequently can return the patient with end-stage heart failure to a near-normal life-style. The physician should be mindful that most patients with heart failure need frequent attention and evaluation. Many patients with moderate to severe heart failure require multidrug regimens and close surveillance to detect electrolyte imbalance or evidence of decompensation at an early stage. Often a tenuous balance exists between pulmonary vascular congestion and orthostatic hypotension, and week-to-week or day-to-day titration of diuretic and vasodilator therapy is required. While the care of the patient with heart failure often requires considerable time and resources, judicious treatment can lead to dramatic improvement and is frequently rewarding to both the patient and physician.

The significance of eosinophils in mild and moderate acute cardiac allograft rejection.

The presence of eosinophils has previously been associated with severe acute cardiac allograft rejection. This appears to be a relatively uncommon finding, judging from our experience and the paucity of information appearing in literature. We report three cases where a prominent infiltrate of eosinophils was noted on endomyocardial biopsy following cardiac transplantation. There was no evidence of severe acute rejection in any of these three patients, and one patient had only mild acute rejection without even focal myocardial necrosis. An infiltrate, which includes eosinophils, does not appear to be restricted to severe acute cardiac allograft rejection. Therefore, when eosinophils are noted in endomyocardial biopsy specimens, decisions to revise the immunosuppressive regimen of cardiac transplant recipients should continue to be based upon established conventional histologic criteria.

Hemodynamic effects of dopexamine hydrochloride infusions of 48 to 72 hours' duration for severe congestive heart failure.

Dopexamine hydrochloride, a new dopaminergic derivative with potent beta 2-agonist activity, was administered to 10 patients with severe congestive heart failure. Initially, the drug was infused at increasing dosage to achieve a maximal tolerated dose and then titrated to maintain acceptable clinical parameters over the next 48 to 72 hours. Cardiac index increased significantly during the initial titration and at peak effect. Tolerance over the duration of the study was noted in most patients, although further increases in cardiac index could usually be achieved by modest increases in the infusion rate. The peak hemodynamic effect was noted at an average infusion rate of 4.8 micrograms/kg/min. Both stroke volume and stroke work indexes increased during dopexamine hydrochloride infusion in association with decreases in mean arterial, right atrial, mean pulmonary artery and pulmonary capillary wedge pressures, systemic vascular resistance and pulmonary arteriolar resistance. Cardiac output increased by 60% during the infusion and this was out of proportion to the 12% increase in heart rate at peak effect. Most of the increase in cardiac index appeared to be due to the strong vasodilatory profile of the medication producing afterload reduction, with direct inotropic and chronotropic effects contributing to a lesser degree. Drug-related side effects occurred in 4 patients and were easily controlled by down-titration. Dopexamine hydrochloride is an effective and well-tolerated sympathomimetic agent that increases cardiac index while promoting vasodilatation.

Systolic anterior motion of the mitral valve as a manifestation of heart transplant rejection.

A 65-year-old white man with acute cardiac allograft rejection had a diagnosis made on the basis of clinical presentation and endomyocardial biopsy. The echocardiogram showed systolic anterior motion of the mitral valve during the episode of rejection. There was no systolic anterior motion on the echocardiogram that was done either before or after the episode of rejection.

Premortem histologic evidence of chronic vascular rejection obtained from percutaneous endomyocardial biopsy: report of a case.

Chronic rejection is characterized by obliterative arteritis of coronary arteries and their branches in the form of myointimal proliferation and diffuse tubular atherosclerosis. Chronic rejection is more difficult to detect than discrete focal obstructive lesions by coronary angiography. We report a case of a 51-year-old woman in whom a biopsy of the right ventricle 14 months after heart transplantation revealed convincing histologic evidence of chronic rejection. A subsequent biopsy of the left ventricle showed subendocardial infarct. Necropsy findings confirmed coronary artery changes of chronic rejection, as well as diffuse subendocardial infarction, which had been suspected clinically. The finding of a small arteriole in a biopsy was fortuitous. However, if such a vessel is present and shows obliterative arteritis, this demonstrates that a premortem histologic diagnosis of chronic rejection is possible.

Comparison of gated cardiac magnetic resonance imaging and two-dimensional echocardiography for the evaluation of right ventricular thrombi: a case report with autopsy correlation.

In a patient who died of complications of severe pulmonary hypertension, right ventricular failure, and sepsis, antemortem two-dimensional (2-D) echocardiography and magnetic resonance imaging (MRI) studies demonstrated a right ventricular mass which at autopsy proved to be thrombus. The diagnostic features of this mass as imaged by these two methods are compared. This case was complicated in that the patient had a history of right atrial myxoma that had been successfully removed three years previously, and a history of several prior pulmonary emboli. Gated MRI depicted the size, shape, and surface characteristics of the mass more clearly than 2-D echocardiography because MRI provided better contrast and spatial resolution. Both techniques were useful in localizing the mass and showing if it was fixed or mobile. Depiction of tumor attachment was unclear with echocardiography but very clear with MRI. MRI also showed a left pulmonary artery thrombus that was not visualized by 2-D echocardiography. Both techniques provided chamber dimension measurements showing enlargement of the right atrium and ventricle. This case demonstrates that gated MRI provides high-quality images of cardiac anatomy and masses. Gated cardiac MRI should be considered at least complementary and potentially superior to two-dimensional echocardiography in the evaluation of intracardiac masses in certain patients.

Breathing pattern abnormalities and arterial oxygen desaturation during sleep in the congestive heart failure syndrome. Improvement following medical therapy.

We observed breathing pattern abnormalities and arterial oxygen desaturation in patients with stable congestive heart failure during overnight polysomnography. To determine whether congestive heart failure was the reason for these abnormalities, we then studied six additional patients before and after treatment of heart failure. Breathing was more abnormal (153 +/- 87 episodes/night) during decompensation of heart failure and improved with medical therapy (72 +/- 100 episodes/night) (p less than 0.05). Abnormal breathing patterns resolved in three patients, improved in two, and were unchanged in one patient after therapy. Allographic cardiac transplantation in one patient whose sleep study remained unchanged after medical therapy was associated with resolution of breathing pattern abnormalities and severe desaturation during sleep. Therapy-related improvement in nocturnal respiratory events suggests congestive heart failure is a contributing factor for breathing abnormalities and arterial oxygen desaturation during sleep.

Cutaneous complications of heart transplantation.

Since July 1984, 12 heart transplants have been performed at the University of Kansas Medical Center During this period, all recipients were screened for any dermatologic problems that may have been present, either before surgery or that may have resulted postoperatively as a consequence of immunotherapy used to suppress heart rejection. This report describes the most common cutaneous findings that in our experience include hypertrichosis, herpes simplex, warts, tinea, and steroid acne. Although these are usually not life-threatening problems, careful attention to the skin and mucous membranes may prevent serious infectious complications, improve personal hygiene, and bolster the patient's self-image.

Hemodynamic and metabolic effects of enalapril in patients with heart failure.

Placebo and enalapril were added on a double-blind basis to conventional treatment in 14 patients with congestive heart failure (CHF), New York Heart Association class II-III. The patients were followed for 14 weeks and their performance was evaluated by a treadmill test, ejection fraction by nuclear scan, cardiothoracic ratio, and Yale Scale score. Metabolic studies were done to test any adverse effects of the drugs. Enalapril decreased arterial pressure and cardiothoracic ratio, and increased ejection fraction. Placebo exerted no significant effects. However, both drugs improved treadmill time and Yale Scale score. No adverse metabolic or clinical effects were observed with either drug. Based on these limited observations we conclude that: Enalapril is a useful ancillary agent to conventional treatment of CHF; it exerts its effects through afterload and preload reduction; and it is safe and well tolerated and has a prolonged duration of action.

Scintigraphic sequelae of superior vena caval obstruction.

The scintigraphic characteristics of superior vena caval obstruction are presented together with a discussion of the relevant vascular anatomy. Alterations in scintigraphic venous blood flow patterns of a patient who underwent two surgical bypass procedures for symptomatic relief of superior vena caval obstruction are shown.