Worse diuretic response was associated with more advanced heart failure, renal impairment, diabetes, atherosclerotic disease and in-hospital worsening heart failure, and predicts mortality and heart failure rehospitalization in this post hoc, hypothesis-generating study.

The incidence of WRF in HFpEF was similar to that previously reported in HFrEF but more frequent with irbesartan than with placebo. WRF after initiation of irbesartan treatment in HFpEF was associated with excess risk, in contrast to WRF occurring with RAAS blockade in HFrEF.

A number of uncontrolled studies have indicated that oral administration of amrinone, a phosphodiesterase inhibitor with potent positive inotropic effects in experimental preparations, may be beneficial in patients with chronic congestive heart failure. The present multicenter trial was designed to prospectively evaluate clinical response and change in exercise tolerance during 12 weeks of amrinone therapy in a double-blind, placebo-controlled protocol. Ninety-nine patients with NYHA functional class 3 or 4 congestive heart failure on digitalis and diuretics, of whom 31 were also receiving captopril, were enrolled. After baseline clinical assessment and determination of exercise tolerance, radionuclide left ventricular ejection fraction, and roentgenographic cardiothoracic ratio, patients were randomly assigned to receive amrinone or placebo, beginning at 1.5 mg/kg tid and increasing to a maximum dosage of 200 mg tid. After 12 weeks of therapy or at the last blinded evaluation in patients who did not complete this protocol, there were no significant differences from baseline values between treatment with amrinone or placebo with regard to symptoms, NYHA functional class, left ventricular ejection fraction, cardiothoracic ratio, frequency and severity of ventricular ectopy, or mortality. Exercise tolerance improved significantly from baseline by 37 + 10% (mean 163 sec) in patients on amrinone and 35 ± 11 % (mean 149 sec) in patients on placebo, but there was no significant difference between treatments. Adverse reactions were significantly more frequent and more severe on amrinone, occurring in 83% of patients and necessitating withdrawal in 34%. Downward adjustment of amrinone dosage because of side effects was responsible for a significantly lower mean total daily dose of 355 vs 505 mg for placebo (p < .001). These findings indicate that oral administration of amrinone is not clinically effective in patients with chronic congestive heart failure, in part because of frequent adverse effects. Circulation 71, No. 5, 96-971, 1985. IN THE LAST DECADE there has been growing interest in new approaches to drug treatment of refractory congestive heart failure. Early investigations centered on drugs that altered the loading conditions of the left ventricle. More recently, agents possessing positive inotropic activity with chemical structures and mechanisms of action different from those of digitalis glycosides or catecholamines have been investigated. ' Amrinone, a bipyridine derivative,2 was the first of these to undergo extensive clinical evaluation. Shortterm therapy with amrinone administered intravenous-*Participating centers and investigators are listed in an appendix to

Over five years, 13 patients with episodic apparent type II atrioventricular (AV) block associated with sinus slowing were seen. This phenomenon occurred only transiently during an acute illness in eight patients (group I) but recurred chronically in five (groupII). For the group as a whole, the mean spontaneous cycle length was 42% longer during the period of AV block compared with periods of 1:1 AV conduction (800 +/- 116 msec to 1138 +/- 489 msec) (P less than 0.05). Electrophysiologic studies in four group I patients showed no abnormalities, whereas abnormalities in AV nodal conduction and refractoriness or provocation of intranodal Mobitz type II AV block (during carotid massage) were observed in three patients in group II and were totally abolished by atropine. In group I patients, apparent type II AV block was self-limited. In the chronic group, recurrent symptoms required insertion of permanent pacemakers in two patients. Simultaneous type II block and sinus slowing appeared to be related to the effects of increased vagal tone on both nodal structures. Intracardiac pacing is not indicated for patients with transient episodes associated with an acute illness, but may be required for symptomatic patients with recurrent episodes.