Exchange of beta-blockers in heart failure patients. Experiences from the poststudy phase of COMET (the Carvedilol or Metoprolol European Trial)

BACKGROUND: The Carvedilol or Metoprolol European Trial (COMET) reported a significant survival benefit for carvedilol, a beta1-, beta2- and alpha1-blocker, vs. metoprolol tartrate, a beta1-selective blocker, in patients with mild-to-severe chronic heart failure (CHF). Patients on treatment with metoprolol might benefit from switching to carvedilol. AIM: To investigate the safety and tolerability of switching beta-blockers in CHF. METHODS: At the end of COMET, the Steering Committee recommended that study medication was stopped without unblinding, and patients were commenced on open-label beta-blockade at a dose equivalent to half the dose of blinded therapy, with subsequent titration to target or maximum tolerated dose. Patients were followed for 30 days. RESULTS: 1321 out of 1440 patients were transitioned to open-label treatment (76.8% to carvedilol). Serious adverse and CHF-related events were respectively 9.4% and 4.7% in those switching from carvedilol to metoprolol and 3.1% and 1.5% in patients switching from metoprolol to carvedilol. Patients who switched from carvedilol to metoprolol showed the highest mortality or hospitalisation rate (12.3%) in comparison with those who switched from metoprolol to carvedilol (3.1%, p<0.001) or who stayed on the same drug (carvedilol: 2.5%, p<0.001; metoprolol: 4.2%, p=0.04). Reducing the initial dose of the second beta-blocker maximised the safety of this strategy. Event rate was higher in patients with more severe heart failure and in those withdrawing from beta-blockade. CONCLUSION: Our data show that switching beta-blockers is a practical, safe and well-tolerated strategy to optimise treatment of CHF. Patients who switched to carvedilol showed the lowest rate of adverse events. A closer clinical monitoring is recommended during transition in high-risk patients.     

Perforation thresholds and safety factors in in vivo coronary laser angioplasty.

Laser angioplasty can cause early (acute perforation) or late (stenosis or aneurysm) complications. To find how much intravascular laser energy can be delivered via a 100 microns core optical fibre passed down a balloon angioplasty catheter without causing angiographic abnormalities up to 10 days later, argon laser energy was delivered percutaneously under radiographic screening to the coronary circulation of 12 normal closed chest dogs. With the balloon inflated, sequential laser pulses were delivered to the same site. Angiograms were recorded before, immediately, and again at one week, after laser delivery. There were two laser-induced perforations (both fatal). Mechanical perforation with the 100 microns fibre occurred four times, but there were no haemodynamic sequelae. To find the acute perforation threshold of similar sized arteries to energy delivered via the bare 100 microns core fibre, the tip of which was held in contact with the luminal surface, 32 argon laser pulses were delivered transluminally in vivo to separate sites in normal rabbit iliac and canine coronary arteries. The acute perforation threshold with energy delivered via the angioplasty catheter lay between 6 and 10 J and that without the balloon angioplasty catheter lay between 3 and 4 J. After delivery of up to 6 J via a balloon angioplasty catheter, there were no angiographic abnormalities at one week. Fibre optic transluminal delivery of laser energy may improve the primary success rate of, and perhaps widen the indications for, coronary angioplasty.     

Maximal oxygen uptake in severe aortic regurgitation: a different view of left ventricular function

Respiratory gas exchange was used to assess left ventricular (LV) function in 22 patients with severe aortic regurgitation (19 men and three women, aged 18 and 70 years, mean 49 years). Anaerobic threshold and symptom-limited maximal oxygen consumption (VO2 max) were measured during treadmill exercise, and the results were compared with conventional echocardiographic and radionuclide indices of LV systolic function. The results were considered with respect to the patients' New York Heart Association functional class. Both rest and exercise LV ejection fractions were variable, but the mean results were similar in all classes. The echocardiographic indices of LV cavity dimensions, fractional shortening, radius/thickness ratio, and systolic wall stress also showed a wide range but with similar mean results in each class. In contrast, VO2 max and anaerobic threshold showed a relationship to functional class. VO2 max was 32.4 +/- 3.4 ml/kg/min in age-matched control subjects; in the patients it was 27.9 +/- 4.7 in class I, 24.7 +/- 5.7 in class II, and 14.2 +/- 2 in the combined class III/IV. Results in patients in classes I and II were similar, but both groups were significantly different from control subjects (p less than 0.05) and from patients in class III/IV (p less than 0.01). About half of the patients with moderate LV dysfunction (judged by reduced VO2 max) were asymptomatic, and LV function was impaired in 4 of 10 patients in class I. Thus, unlike conventional indices of LV function, VO2 max appeared capable of distinguishing patients with moderate-to-severe LV dysfunction from those with little or no LV dysfunction. Measurement of respiratory gas exchange appears to be a valid and useful supplementary means of assessing LV function in severe aortic regurgitation. Further long-term evaluation is required.     

Acute haemodynamic comparison of amrinone and pirbuterol in chronic heart failure. Additional effects of isosorbide dinitrate.

A randomised, within patient comparison was made in patients with severe chronic heart failure, to study the acute haemodynamic effects of oral agents which have inotropic and vasodilator properties. A non-glycosidic non-adrenergic positive inotropic agent with vasodilator properties (amrinone) was compared with a beta-agonist which has vasodilator and positive inotropic effects (pirbuterol). To assess whether combined treatment with a venodilator might be advantageous, the effect of adding isosorbide dinitrate was studied. Oral amrinone or pirbuterol were given in random order to each of 13 patients, on successive days, and oral isosorbide dinitrate was added after two-and-a-half hours. Control values before amrinone or pirbuterol were similar, and both drugs increased cardiac index while reducing left ventricular filling pressure, right atrial pressure, and systemic vascular resistance. Heart rate and blood pressure were unchanged. The magnitude of the changes caused by amrinone and pirbuterol were not significantly different. The addition of isosorbide dinitrate caused further falls in left ventricular filling pressure and right atrial pressures, and a fall in heart rate with each drug. Other measurements remained unchanged. Although amrinone and pirbuterol have different pharmacological properties, their acute haemodynamic effects in patients with chronic heart failure are indistinguishable.     

Patients who have dilated cardiomyopathy must have a trial of bridge to recovery: the case against that proposition

The idea that patients who have dilated cardiomyopathy (presumably a large heart with near-normal coronary arteries) must have a trial of bridge to recovery is risible. Many such patients should be managed so that they go directly to transplantation and others may be better treated with drug therapy. Some may be more suited to destination therapy. What is needed in this field is more precise terminology, clearer statements of clinical intent at the time of device insertion, improved characterization of patients, more accurate clinical assessment, and above all more information from randomized clinical trials.     

The safety of amiodarone in patients with heart failure

BackgroundUncertainty persists about the safety and efficacy of amiodarone for the management of heart failure.Methods and ResultsWe randomized 3029 patients with chronic heart failure to receive carvedilol or metoprolol and followed patients for a median of 58 months. One hundred fifty-five of 1466 patients in New York Heart Association (NYHA) Class II and 209 of 1563 in Class III or IV received amiodarone at baseline. Persistence with amiodarone treatment was high and 66% received amiodarone after 4 years. During follow-up, 38.7% and 58.9% of patients receiving amiodarone in NYHA Classes II and III + IV died versus 26.2% and 43.3% not receiving amiodarone (P < .001). This difference was maintained in multivariable analysis (hazard ratio [HR] 1.5, 95% confidence interval [CI] 1.2–1.7, P < .001). The difference was explained by an increased risk of death due to circulatory failure (HR 2.4, CI 1.9–3.1, P < .001) in patients receiving amiodarone. Sudden death was not different (HR 1.07, CI 0.8–1.4, P = .7). The increased risk was similar across NYHA classes with HR of 1.60 (CI 1.2–2.1, P < .001) in NYHA Class II versus 1.58 (CI 1.3–1.9, P < .001) in Classes III + IV.ConclusionsTreatment with amiodarone was associated with an increased risk of death from circulatory failure independent of functional class.