Relation between heart rate, heart rhythm, and reverse left ventricular remodelling in response to carvedilol in patients with chronic heart failure: a single centre, observational study. (Cardiovascular Medicine).

Objective: To determine whether the process of reverse left ventricular remodelling in response to carvedilol is dependent on baseline heart rate (BHR), heart rhythm, or heart rate reduction (HRR) in response to carvedilol.

Design: Retrospective analysis of serial echocardiograms in 257 patients with chronic systolic heart failure at baseline and at 12-18 months after starting carvedilol. Reverse left ventricular remodelling was determined by changes in left ventricular end diastolic dimension (LVEDD), end systolic dimension (LVESD), and fractional shortening (LVFS).

Setting: Heart failure clinic within a university teaching hospital.

Main outcome measures: Changes in LVEDD, LVESD, and LVFS.

Results: LVEDD and LVESD decreased by 2.6 (0.4) mm and 4.9 (0.5) mm, respectively (mean (SEM)), and LVFS increased by 4.3 (0.5)% (all p < 0.0001 v baseline). Simple regression revealed no significant relation between BHR or HRR and the changes in LVEDD, LVESD, or LVFS. Stratification of patients into high and low BHR groups (above and below the mean) or according to the baseline heart rhythm (sinus rhythm v atrial fibrillation) showed no differences between groups in the extent of reverse left ventricular remodelling. Improvements in left ventricular function and dimensions were associated with significant improvements in New York Heart Association functional class.

Conclusions: The benefits of carvedilol in terms of reverse left ventricular remodelling and symptomatic improvement in patients with chronic heart failure are independent of BHR, heart rhythm, and the HRR that occurs in response to carvedilol.

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The importance of baseline heart rate (BHR) and treatment induced heart rate reduction (HRR) as predictors of the response to [beta] blockers in chronic heart failure is controversial. Some investigators have reported that the BHR is predictive of symptomatic improvement' and improvement in left ventricular function in response to [beta] blockade, (2) while others have found no such relations. (3-5) Post hoc stratification of patients in the US carvedilol heart failure programme (6) into groups above and below the mean BHR showed that the mortality benefit of carvedilol compared with placebo was only significant in the group with a high BHR. Recently, the CIBIS II (cardiac insufficiency bisoprolol study) investigators (7) confirmed that BHR was an independent predictor of mortality in patients with chronic heart failure. The benefit of bisoprolol in terms of survival and the need for hospital admission was, however, independent of the BHR and the HRR that occurred during the first two months of bisoprolol tre atment. (7) In addition, these investigator reported that the beneficial response to bisoprolol was observed only in patients in sinus rhythm and not in those with atrial fibrillation. They suggested that baseline heart rhythm rather than heart rate may be an important determinant of the response to [beta] blocker treatment in heart failure.

In order to investigate further the importance of BHR, cardiac rhythm, and HRR in determining the response to [beta] blocker treatment in chronic heart failure, we analysed the relation between these variables and echocardiographic left ventricular remodelling in response to carvedilol in a large consecutive cohort of patients attending a heart failure clinic.

METHODS

Study population

The study population was derived from 429 consecutive patients who were started on carvedilol for chronic systolic heart failure at our institution and who had been followed for at least 12 months thereafter. All patients had been receiving treatment for heart failure for at least three months before starting carvedilol. One hundred and six patients (25%) were withdrawn from carvedilol treatment within the first 12 months because of death (32), heart transplantation (28), or other serious adverse events (46). Another 66 patients were excluded from the echocardiographic analysis: 52 (12%) had technically unsatisfactory echocardiographic studies, and 14 (3%) did not undergo a second scan. Reverse left ventricular remodelling was assessed in the remaining 257 patients (60%) who underwent serial echocardiograms at baseline and between 12-18 months after starting carvedilol.

Carvedilol administration

Carvedilol was begun at a dose of 3.125 mg twice daily and was force titrated, at two weekly intervals, to a target dose of 25 mg twice daily for body weight 85 kg, or 50 mg twice daily for body weight > 85 kg, as tolerated.

Assessment and follow up

All patients were assessed clinically at baseline and at three, six, and 12 months, and then at six monthly intervals. Clinical status was assessed at each visit, including evaluation of New York Heart Association (NYHA) functional class, resting heart rate and rhythm, blood pressure, and cardiac examination.…