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CLINICAL STUDY

Nonselective beta-adrenergic blocking agent, carvedilol, improves arterial baroflex gain and heart rate variability in patients with stable chronic heart failure

^a Department of Cardiology, Centro Medico di Montescano, "S. Maugeri" Foundation, IRCCS, Pavia, Italy

Manuscript received July 29, 1999; revised manuscript received April 10, 2000, accepted June 15, 2000.

Reprint requests and correspondence: Dr. Andrea Mortara, Division of Cardiology, Centro Medico di Montescano, "S. Maugeri" Foundation, IRCCS, Montescano, Pavia, Italy
amortara{at}fsm.it

OBJECTIVES

The purpose of this study was to investigate in a case-controlled study whether carvedilol increased baroreflex sensitivity and heart rate variability (HRV).

BACKGROUND

In chronic heart failure (CHF), beta-adrenergic blockade improves symptoms and ventricular function and may favorably affect prognosis. Although beta-blockade therapy is supposed to decrease myocardial adrenergic activity, data on restoration of autonomic balance to the heart and, particularly, on vagal reflexes are limited.

METHODS

Nineteen consecutive patients with moderate, stable CHF (age 54 ± 7 years, New York Heart Association [NYHA] class II to III, left ventricular ejection fraction [LVEF] 24 ± 6%), treated with optimized conventional medical therapy, received carvedilol treatment. Controls with CHF were selected from our database on the basis of the following matching criteria: age ± 3 years, same NYHA class, LVEF ± 3%, pulmonary wedge pressure ± 3 mm Hg, peak volume of oxygen ± 3 ml/kg/min, same therapy. All patients underwent analysis of baroreflex sensitivity (phenylephrine method) and of HRV (24-h Holter recording) at baseline and after six months.

RESULTS

Beta-blockade therapy was associated with a significant improvement in symptoms (NYHA class 2.1 ± 0.4 vs. 1.8 ± 0.5, p < 0.01), systolic and diastolic function (LVEF 23 ± 7 vs. 28 ± 9%, p < 0.01; pulmonary wedge pressure 17 ± 8 vs. 14 ± 7 mm Hg, p < 0.05) and mitral regurgitation area (7.0 ± 5.1 vs. 3.6 ± 3.0 cm², p < 0.01). No significant differences were observed in either clinical or hemodynamic indexes in control patients. Phenylephrine method increased significantly after carvedilol (from 3.7 ± 3.4 to 7.1 ± 4.9 ms/mm Hg, p < 0.01) as well as RR interval (from 791 ± 113 to 894 ± 110 ms, p < 0.001), 24-h standard deviation of normal RR interval and root mean square of successive differences (from 56 ± 17 to 80 ± 28 ms and from 12 ± 7 to 18 ± 9 ms, all p < 0.05), while all parameters remained unmodified in controls. During a mean follow-up of 19 ± 8 months a reduced number of cardiac events (death plus heart transplantation, 58% vs. 31%) occurred in those patients receiving beta-blockade.

CONCLUSIONS

Besides the well-known effects on ventricular function, treatment with carvedilol in CHF restores both autonomic balance and the ability to increase reflex vagal activity. This protective mechanism may contribute to the beneficial effect of beta-blockade treatment on prognosis in CHF.

Abbreviations and Acronyms   ANOVA = analysis of variance   BRS = baroreflex sensitivity   CHF = chronic heart failure   HRV = heart rate variability   LVEF = left ventricular ejection fraction   NYHA = New York Heart Association   rMSSD = root mean square of successive differences   SAP = systolic arterial pressure   SDNN = 24-h standard deviation of normal RR interval

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