A multicenter, randomized, double-blind, placebo-controlled trial of pimobendan, a new cardiotonic and vasodilator agent, in patients with severe congestive heart failure.

Pimobendan, a new oral cardiotonic and vasodilator agent, increases myocardial contractile force through specific inhibition of phosphodiesterase type III and increased calcium sensitivity of the myocardial contractile elements. The effects of pimobendan on left ventricular performance and maximal exercise capacity were studied in a multicenter, randomized, double-blind, placebo-controlled trial involving 52 patients with severe congestive heart failure despite diuretics, digoxin, and angiotensin-converting enzyme inhibitors. The acute hemodynamic evaluation included three single doses of 2.5, 5.0, and 10.0 mg of oral pimobendan, which was subsequently administered at a daily dose of 5 or 10 mg for 4 weeks. Acute administration of pimobendan significantly increased the resting cardiac index and lowered pulmonary capillary wedge pressure in a dose-dependent manner, whereas heart rate and systemic arterial pressure were not substantially altered. Patients receiving pimobendan, 5 and 10 mg daily, had a significantly greater increase in maximal exercise duration than those receiving placebo, that is, 144 +/- 30 and 124 +/- 33 seconds versus 58 +/- 25 seconds (p = 0.05). Peak oxygen uptake increased by 1.7 +/- 0.8 and 2.2 +/- 1.3 ml/kg/min in patients receiving pimobendan at a daily dose of 5 and 10 mg, respectively, whereas it decreased by 0.1 +/- 0.6 ml/kg/min in patients receiving placebo (p = 0.06). Thus pimobendan acutely improves resting left ventricular performance and chronically increases exercise duration and peak oxygen uptake in patients with severe congestive heart failure concomitantly treated with digoxin, diuretics, and angiotensin-converting enzyme inhibitors.     

Sexually transmitted diseases in a population of intravenous drug users: association with seropositivity to the human immunodeficiency virus (HIV)

The association between human immunodeficiency virus (HIV) seropositivity and a history of sexually transmitted diseases (STDs), evidence of STDs on physical examination, and sexual and drug use practices was studied in a population of 2921 intravenous drug users (IVDUs) in Baltimore during 1988 and 1989. Overall, 24.1% were HIV-seropositive at baseline, and 60% reported a history of an STD. A significant association was found between HIV seropositivity and a history of syphilis (P = .04); both were more frequent among homosexual/bisexual men than among heterosexual IVDUs. In multivariate analysis, a history of syphilis was independently associated with HIV seroprevalence in homosexual/bisexual male IVDUs, of whom 90% reported a history of sexual intercourse with women. Cocaine injection was independently associated with HIV seropositivity but not a history of syphilis on multivariate analysis. STDs, indicative of unsafe sex practices, are common in this population; efforts are needed to prevent sexual transmission of HIV infection among IVDUs and their sex partners.     

The preferred approach for mitral valve surgery after CABG: right thoracotomy, hypothermia and avoidance of LIMA-LAD graft

BACKGROUND AND AIM OF THE STUDY: An alternative to avoid redo sternotomy in patients with patent left internal mammary artery-left anterior descending coronary artery (LIMA-LAD) grafts undergoing mitral valve surgery is right thoracotomy with moderate-deep hypothermia (approximately 20 degrees C) and fibrillatory arrest without aortic cross-clamping. Few reports exist which directly compare re-sternotomy and right thoracotomy. METHODS: Between July 1992 and February 2000, 47 patients (39 males, eight females; median age 66 years; range: 41-83 years; 41 in NYHA class III or IV) with patent LIMA-LAD grafts underwent mitral valve surgery. Thirty-seven patients were approached through a right thoracotomy with moderate-deep hypothermia (median 20 degrees C) and fibrillatory arrest (right thoracotomy group), and 10 were approached through a re-sternotomy, with aortic cross-clamping and cardioplegic arrest. The median ejection fraction was 42% (range: 20-71%). Univariate analysis was used to determine predictors of outcome, as well as to evaluate differences in characteristics between groups. RESULTS: Operative mortality (OM) and perioperative myocardial infarction for the entire cohort was 11% and 10%, respectively, and there were no inter-group differences. No preoperative characteristics were associated with OM. Two LIMA-LAD graft injuries occurred in the re-sternotomy group compared with none in the right thoracotomy group (20% versus 0%, p = 0.04). Transfusion requirements were also greater in the redo sternotomy group (median 7 versus 2 packed red blood cell units, p = 0.04). CONCLUSION: Right thoracotomy with moderate-deep hypothermia and fibrillatory arrest is the preferred approach for reoperative mitral valve surgery after coronary artery bypass grafting in the presence of patent LIMA-LAD grafts. These data suggest that this approach is associated with decreased incidence of LIMA-LAD graft injury, as well as reduced transfusion requirements.     

Decreased venous distensibility in essential hypertension: lack of systemic hemodynamic correlates.

Venous distensibility in essential hypertension has been reported to be unchanged or decreased; its pathophysiologic role is uncertain. In 27 male hypertensive patients and 21 normotensive control subjects, forearm venous distensibility and capillary filtration rate at 30 cm of H2O distending pressure were measured by strain gauge plethysmography. Plasma renin activity (PRA), plasma volume (PV) by the Evans blue dye dilution technique, mean arterial pressure (MAP) by cuff, and cardiac output (CO) by the CO2 rebreathing method were also measured. Compared to values in normotensive control subjects, forearm venous distensibility in hypertensive subjects was decreased (P less than 0.05); the forearm venous pressure-volume curves (deflation phase) were shifted in the direction of the pressure axis (P less than 0.02); and the capillary filtration rate was increased (P less than 0.05). Venous distensibility changes in hypertensive subjects were unrelated to PRA, MAP, PV, CO, stroke volume, and total peripheral resistance. These findings confirm previous reports of decreased venous distensibility in hypertension and provide direct evidence for increased capillary filtration rate. In view of the lack of significant correlation between venous distensibility and the measured hemodynamic parameters, a patho-physiologic role for venous distensibility in hypertension could not be established.     

Nitrates for congestive heart failure

The use of nitrates in various sublingual, oral, topical and intravenous forms of treatment of patients with congestive heart failure (CHF) is based on their efficacy in dilating capacitance vessels and reducing elevated ventricular diastolic pressure on both the left and right sides of the heart. Their modest arteriolar and arterial dilating effect may also decrease aortic impedance and produce a slight increase in stroke volume despite the reduction in preload. This favorable hemodynamic response requires relatively large doses of the nitrates but these doses are remarkably well tolerated in the majority of patients with CHF. In chronic CHF there has been evidence from small controlled trials of clinical efficacy (increased exercise tolerance and reduction in symptomatology) as well as hemodynamic efficacy. The combination of nitrates with a more potent arteriolar dilator such as hydralazine or minoxidil has produced a more striking acute hemodynamic benefit. Long-term response to such combined therapy is currently the subject of a Veterans Administration cooperative study. The current recommended approach to nitrate therapy in patients with CHF is to use the dosage necessary to normalize ventricular filling pressure. This can be best assessed in the clinic by monitoring jugular venous pressure. This response often requires dosages of isosorbide dinitrate of 160 to 320 mg daily. Transdermal preparations of nitroglycerin may give more constant blood levels but a large dosage is usually required to produce a sustained hemodynamic effect (40 to 80 cm2).(ABSTRACT TRUNCATED AT 250 WORDS)     

Body composition changes in children receiving human growth hormone

Skinfold thickness was found to decrease during the first 6–10 wk and then remain constant when human growth hormone therapy was begun in 34 growth hormone-deficient children. Linear growth increased at a constant rate during the first 6 mo. Two children, who routinely received their injection in the same arm at the same site, developed a localized area of markedly diminished subcutaneous fat at the injection site, Height, weight, total-body potassium, and triceps skinfold thickness were measured at 2-mo intervals in nine children receiving human growth hormone. Total-body potassium was measured with the 54-Nal detector whole-body counter of the Brookhaven National Laboratory. The study extended over a period of 20 consecutive mo. Triceps skinfold thickness rapidly decreased during the initiation of therapy with growth hormone, and returned to pretreatment values during a 5-mo control period when therapy was temporarily discontinued. Rate of weight gain was most rapid during this 5-mo control period and was reduced during two periods when growth hormone was being administered. Total body potassium and height increased very little during the control period when weight gain was greatest, and both increased rapidly during the two periods of growth hormone treatment. The data show clearly the initial changes in body fat and lean tissue that occur when human growth hormone is administered to children with growth deficiency.     

Role of vasoconstrictor mechanisms in the control of left ventricular performance of the normal and damaged heart.

The effect on the left ventricle of changes in the state of the arterial vasculature is best identified by utilizing calculations of pulsatile rather than steady flow phenomena. Impedance is the most satisfactory term to describe this effect. The normal ventricle compensates for changes in impedance largely by changes in preload, but the damaged heart loses this compensatory ability and its stroke volume becomes inversely related to outflow resistance. Patients with heart failure behave in a similar fashion and pharmacologic vasodilation may induce marked improvement in left ventricular pump function. Inappropriate vasoconstriction in heart failure may result from stimulation of the sympathetic or renin-angiotensin system. Early experience with converting enzyme inhibitors suggests that blockade of the formation of angiotensin II may be a useful means of treating some patients with heart failure.     

Doppler echocardiographic comparison of the Carpentier and Duran anuloplasty rings versus no ring after mitral valve repair for mitral regurgitation

To compare the hemodynamic results of different anuloplasty techniques of primary valve repair for mitral regurgitation, 122 patients were prospectively studied with Doppler echocardiograms 5 to 10 days after operation. Seventy-seven patients had mitral valve prolapse, 27 had coronary artery disease, 13 patients had rheumatic mitral valve lesions and 5 patients had infective endocarditis. Forty-eight patients received the flexible Duran ring, 46 received the more rigid Carpentier ring and 28 patients received no ring. Doppler echocardiography demonstrated a significant decrease in mitral valve area estimated by the pressure half-time method in patients who received either a Carpentier (2.6 +/- 0.8 cm2) or Duran ring (2.8 +/- 0.8 cm2) when compared with patients who received no ring (3.2 +/- 0.7 cm2) (p = 0.01). No significant differences were observed for peak transmitral diastolic velocity, peak transmitral diastolic gradient, or the grade of mitral regurgitation by color flow Doppler mapping between patients with and without rings. The etiology of mitral disease and concomitant surgical procedures accompanying mitral valve repair did not significantly influence mitral valve area, peak velocity or peak gradient. These data suggest that Carpentier and Duran rings decrease the hemodynamic mitral valve area; however, the decrease in valve area is small and not associated with a clinically important increase in transvalvular gradient.