Grady H. Hendrix

Effect of Oral Milrinone on Mortality in Severe Chronic Heart Failure

BACKGROUND Milrinone, a phosphodiesterase inhibitor, enhances cardiac contractility by increasing intracellular levels of cyclic AMP, but the long-term effect of this type of positive inotropic agent on the survival of patients with chronic heart failure has not been determined. METHODS We randomly assigned 1,088 patients with severe chronic heart failure (New York Heart Association class III or IV) and advanced left ventricular dysfunction to double-blind treatment with (40 mg of oral milrinone daily (561 patients) or placebo (527 patients). In addition, all patients received conventional therapy with digoxin, diuretics, and a converting-enzyme inhibitor throughout the trial. The median period of follow-up was 6.1 months (range, 1 day to 20 months). RESULTS As compared with placebo, milrinone therapy was associated with a 28 percent increase in mortality from all causes (95 percent confidence interval, 1 to 61 percent; P = 0.038) and a 34 percent increase in cardiovascular mortality (95 percent confidence interval, 6 to 69 percent; P = 0.016). The adverse effect of milrinone was greatest in patients with the most severe symptoms (New York Heart Association class IV), who had a 53 percent increase in mortality (95 percent confidence interval, 13 to 107 percent; P = 0.006). Milrinone did not have a beneficial effect on the survival of any subgroup. Patients treated with milrinone had more hospitalizations (44 vs. 39 percent, P = 0.041), were withdrawn from double-blind therapy more frequently (12.7 vs. 8.7 percent, P = 0.041), and had serious adverse cardiovascular reactions, including hypotension (P = 0.006) and syncope (P = 0.002), more often than the patients given placebo. CONCLUSIONS Our findings indicate that despite its beneficial hemodynamic actions, long-term therapy with oral milrinone increases the morbidity and mortality of patients with severe chronic heart failure. The mechanism by which the drug exerts its deleterious effects is unknown.

Effects of Vesnarinone on Morbidity and Mortality in Patients with Heart Failure

BACKGROUND Inotropic therapy, other than with digitalis glycosides, has had limited success in patients with chronic congestive heart failure. We investigated whether vesnarinone, a new positive inotropic agent, reduces morbidity and mortality and improves the quality of life of patients with symptomatic heart failure. METHODS Patients receiving concomitant therapy with digoxin (87 percent) and an angiotensin-converting-enzyme inhibitor (90 percent) who had ejection fractions of 30 percent or less were randomly assigned to receive double-blinded therapy with 60 mg of vesnarinone per day, 120 mg of vesnarinone per day, or placebo. Afer 253 patients had been enrolled, randomization to the 120-mg vesnarinone group had to be stopped because of a significant increase in early mortality in this group. Thereafter, patients were randomly assigned only to 60 mg of vesnarinone per day (a total of 239 patients) or placebo (a total of 238 patients). RESULTS Significantly fewer patients in the group receiving 60 mg of vesnarinone than in the group receiving placebo (26 vs. 50 patients; P = 0.003) died or had worsening heart failure during the six-month study period. The reduction in risk was 50 percent (95 percent confidence interval, 20 to 69 percent). Similarly, there was a 62 percent reduction (95 percent confidence interval, 28 to 80 percent) in the risk of dying from any cause among the patients receiving vesnarinone. Furthermore, quality of life improved to a greater extent in the vesnarinone group than in the placebo group over 12 weeks (P = 0.008). The principal side effect associated with vesnarinone was reversible neutropenia, which occurred in 2.5 percent of the patients. CONCLUSIONS Six months of therapy with 60 mg of vesnarinone per day resulted in lower morbidity and mortality and improved the quality of life of patients with congestive heart failure. However, a higher dose of vesnarinone (120 mg per day) increased mortality, suggesting that this drug has a narrow therapeutic range; the long-term effects of vesnarinone are unknown.

Predictors of outcome for aortic valve replacement in patients with aortic regurgitation and left ventricular dysfunction: A change in the measuring stick

Although left ventricular function is generally regarded as a key determinant of prognosis in aortic regurgitation, predictors of outcome of aortic valve replacement based on this factor have recently been questioned. This study was performed to examine the role of indexes of left ventricular function in predicting the outcome of surgery in patients with aortic regurgitation and left ventricular dysfunction. Fourteen patients with aortic regurgitation with a preoperative ejection fraction of less than 0.55 (average 0.45 +/- 0.02) who underwent aortic valve replacement were studied. The patients had 82 (58%) of a possible 140 predictors of negative outcome preoperatively, but 12 of the 14 patients had a decrease in symptoms and an increase in ejection fraction into the normal range after operation (average postoperative ejection fraction 0.59 +/- 0.04). Although improvement occurred despite the presence of many negative predictors of outcome, there was a significant correlation between postoperative ejection fraction and eight of the tested preoperative predictors. Preoperative end-systolic dimension correlated best (r = -0.91) with postoperative ejection fraction. An end-systolic dimension of 60 mm correlated with a postoperative ejection fraction of 0.55. The results indicate that preoperative ventricular function is still an important determinant of outcome of aortic valve replacement for aortic regurgitation. However, current medical and surgical techniques permit a better prognosis in the presence of reduced ventricular function than was previously considered possible.

Incidence of acute myocardial infarction in patients with exercise-induced silent myocardial ischemia

Fifty-five patients with angiographically proved coronary artery disease (CAD) underwent Bruce protocol exercise stress testing with thallium-201 imaging. Twenty-seven patients (group I) showed myocardial hypoperfusion without angina pectoris during stress, which normalized at rest, and 28 patients (group II) had a similar pattern of reversible myocardial hypoperfusion but also had angina during stress. Patients were followed for at least 30 months. Six patients in group I had an acute myocardial infarction (AMI), 3 of whom died, and only 1 patient in group II had an AMI (p = 0.05), and did not die. Silent myocardial ischemia uncovered during exercise stress thallium testing may predispose to subsequent AMI. The presence of silent myocardial ischemia identified in this manner is of prognostic value, independent of angiographic variables such as extent of CAD and left ventricular ejection fraction.

Preoperative Evaluation of Cardiac Risk Using Dobutamine-Thallium Imaging in Vascular Surgery

Coronary artery disease is frequently present in patients undergoing evaluation for reconstructive peripheral vascular surgery. Dobutamine-thallium imaging has been shown to be a reliable and sensitive noninvasive method for the detection of significant coronary artery disease. Eighty-seven candidates for vascular reconstruction underwent dobutamine-thallium imaging. Forty-eight patients had an abnormal dobutamine-thallium scan. Twenty-two patients had infarct only, while 26 had reversible ischemia demonstrated on dobutamine-thallium imaging. Fourteen of 26 patients with reversible ischemia underwent cardiac catheterization and 11 showed significant coronary artery disease. Seven patients underwent preoperative coronary artery bypass grafting or angioplasty. There were no postoperative myocardial events in this group. Three patients were denied surgery on the basis of unreconstructible coronary artery disease, and one patient refused further intervention. Ten patients with reversible myocardial ischemia on dobutamine-thallium imaging underwent vascular surgical reconstruction without coronary revascularization and suffered a 40% incidence of postoperative myocardial ischemic events. Five patients were denied surgery because of presumed significant coronary artery disease on the basis of the dobutamine-thallium imaging and clinical evaluation alone. Thirty-nine patients with normal dobutamine-thallium scans underwent vascular reconstructive surgery with a 5% incidence of postoperative myocardial ischemia. Dobutamine-thallium imaging is a sensitive and reliable screening method which identifies those patients with coronary artery disease who are at high risk for perioperative myocardial ischemia following peripheral vascular surgery.

Surgical ligation of an anomalous left coronary artery arising from the pulmonary artery in an adult

Abstract A case report of surgical ligation of an anomalous left coronary artery in an adult has been presented. This rarity in the adult has been compared to the other few reports noted in the literature and valuable prognostic signs are emphasized on the physical examination. With the limited case reports in the older individual, it appears that good retrograde flow from the right coronary artery through the collaterals and left coronary artery into the pulmonary artery is of extreme importance prior to consideration for surgical intervention. Additional long-term follow-up evaluation of older patients with this malformation is needed for definitive evaluation of the therapeutic procedures undertaken. The recent advances in the technique of coronary angiography promise to be an aid in solving this problem.

Use of indicator dilution techniques to determine patency of internal mammary artery implants

Abstract Indicator-dilution indocyanine green dye curves were inscribed by injecting into the internal mammary artery and sampling from the coronary sinus in six patients being studied postoperatively after left internal mammary artery implants. The results were predictable from the internal mammary arteriograms; patients with obvious collateral flow on arteriography had immediate appearance of indocyanine green indicator in the coronary sinus and patients with occluded implants prior to entering the myocardium had only systemic circulation of indocyanine green. One patient with a patent vessel into the myocardium but with no evidence of collateral flow had an early but dispersed curve indicating that some myocardial perfusion was occurring if the implant remained patent but whose arteriograms otherwise pointed to a poor result.