Effects of carvedilol on left ventricular diastolic function and chamber volumes in advanced heart failure.
OBJECTIVE
Carvedilol treatment in chronic heart failure (CHF) demonstrated to reduce mortality and rehospitalisation, and improvement of cardiac systolic function with reduction of left ventricular volumes and remodelling. The effects of the drug on left ventricular (LV) filling are less studied. Systolic dysfunction is often associated to diastolic alteration, pseudonormal and restrictive filling pattern are related with poor prognosis. In this study we evaluated diastolic cardiac modifications during carvedilol therapy at early and long term in patients with advanced CHF and pseudonormal or restrictive filling pattern by echo Doppler method.


METHODS
We studied 59 patients with severe but stable CHF (40 in class NYHA III and 19 in class NYHA IV) with both systolic and diastolic dysfunction due to idiopathic or ischemic cardiomyopathy. Group I (n=32) received preceding treatment plus carvedilol and Group II (n=27) continued standard therapy with ACE-inhibitors, diuretics, digossin and vasodilators. In all subjects were evaluated LV volumes mass and ejection fraction (EF). Therefore, we studied transmitral filling parameters: Early filling wave (E), atrial filling wave (A), E/A ratio, deceleration time of E (DT) and isovolumetric releasing time (IVRT) by echo Doppler method.


RESULTS
After 4 months of therapy carvedilol group showed a significant increase of A wave (p<0.001) DT (p<0.0001) and IVRT (p<0.0001), and significant reduction of E/A ratio (p<0.0005) respect to Group II. Any significant changes were observed for volumes mass and EF. Transmitral Doppler measurements remained unchanged or further ameliorated at 12 months (A p<0.0005; DT p<0.00002; IVRT p<0.000004; E/A p<0.0008), we also observed E wave reduction (p<0.001) in Group I respect to controls. Besides, after 1 year of follow-up we observed a reduction of systolic volume (p<0.001) pulmonary pressure (p<0.0001) and consequent increase of EF (p<0.001) in group treated with beta-blockers. Multivariate analysis demonstrated that Doppler modification were minimally related to heart rate and blood pressure reduction.


CONCLUSIONS
Carvedilol treatment improve diastolic function in CHF with severe diastolic impairment driving restrictive or pseudonormal filling pattern towards altered pattern at early time. These changes remained also after 1 year of therapy and appeared to precede increase of systolic function and improvement of emodynamic status.
Palazzuoli
A
A
Department of Internal Medicine and Metabolic Diseases, University of Siena, Siena, Italy. palazzuoli2@unisi.it
Quatrini
I
I
Vecchiato
L
L
Scali
C
C
De Paola
V
V
Iovine
F
F
Martini
G
G
Nuti
R
R
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000368:Aged; D002227:Carbazoles / Q000494:pharmacology* / Q000627:therapeutic use; D000077261:Carvedilol; D003971:Diastole / Q000187:drug effects*; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D008297:Male; D011412:Propanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D016277:Ventricular Function, Left / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol