Effects of carvedilol on ventriculo-arterial coupling in patients with heart failure.

BACKGROUND: Ventriculo-arterial coupling, defined as the ratio of the effective afterload (Ea) to contractility (Ees), reflects the mechano-energetic performance of the heart and is increased in chronic heart failure (CHF); the aim of treatment is to reduce its value. We studied the effect of carvedilol on the Ea/Ees ratio in patients with CHF treated with ACE-inhibitors, diuretics, and digoxin. METHODS: Between November 1999 and October 2001, 36 consecutive ambulatory patients (aged 31 to 76 years) with stable CHF and idiopathic or hypertensive cardiomyopathy, in sinus rhythm and with a left ventricular ejection fraction < or = 40%, were started on carvedilol and the dose was increased to the maximum tolerated. Ees was calculated as the left ventricular systolic pressure--taken as the systolic arterial pressure measured using the cuff manometer simultaneously with two-dimensional echocardiographic recordings--divided by the left ventricular end-systolic volume. Ea was measured as the ratio of the left ventricular systolic pressure to the stroke volume. All patients were investigated prospectively after 6 and 12 months of treatment. RESULTS: Out of 36 patients, 4 did not tolerate the drug and were dropped out. At 6.35 +/- 1 months, the daily dosage of carvedilol was 49.7 +/- 21 mg. The NYHA functional class improved from 1.52 +/- 0.67 to 1.29 +/- 0.53 (p = 0.017), the heart rate markedly diminished from 73.6 +/- 13.3 to 60.8 +/- 10.8 b/min (p < 0.001) and so did Ea (3.35 +/- 0.91 to 2.84 +/- 0.93, p = 0.001). Peripheral resistances and Ees did not change. Therefore, the decrease in the Ea/Ees ratio (2.61 +/- 0.78 vs 2.19 +/- 0.89, p = 0.004) and the related increase in left ventricular ejection fraction (28.8 +/- 5.68 vs 33.3 +/- 7.5%, p < 0.001) were due to the decrease in Ea, while Ees did not vary significantly. Moreover, the Ea reduction was related linearly to the decrease in heart rate (r = 0.46, p = 0.001). There was no change in diuretic or ACE-inhibitor dosing during carvedilol titration. At 14.7 +/- 2 months of follow-up, no further variation occurred, short of a trend toward a slight increase in Ees (1.38 +/- 0.49 to 1.58 +/- 0.65, p = 0.07). CONCLUSIONS: Carvedilol, added to the conventional therapy of CHF, improves left ventricular performance and reduces the Ea/Ees ratio by decreasing Ea, mainly through a reduction in heart rate. This effect is already evident at 6 months and persists later on, while only after 12 months does Ees tend to increase slightly.