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Effects of carvedilol on left ventricular diastolic function and chamber volumes in advanced heart failure
A Palazzuoli1, I Quatrini, L Vecchiato
1Department of Internal Medicine and Metabolic Diseases, University of Siena, Siena, Italy. palazzuoli2@unisi.it
Insights
Carvedilol improves diastolic function in chronic heart failure (CHF) patients with severe diastolic impairment. These positive effects on left ventricular filling patterns persist long-term, preceding improvements in systolic function.
Area of Science:
- Cardiology
- Pharmacology
- Echocardiography
Background:
- Chronic heart failure (CHF) is associated with impaired systolic and diastolic function.
- Diastolic dysfunction, particularly pseudonormal and restrictive filling patterns, correlates with poor prognosis in CHF.
- Carvedilol is known to reduce mortality and improve systolic function in CHF, but its effects on diastolic function are less understood.
Purpose of the Study:
- To evaluate the effects of carvedilol on left ventricular (LV) diastolic function in patients with advanced CHF and pseudonormal or restrictive filling patterns.
- To assess early and long-term changes in diastolic parameters during carvedilol therapy.
- To investigate the relationship between diastolic modifications and systolic function improvement.
Main Methods:
- A study involving 59 patients with severe but stable CHF and both systolic and diastolic dysfunction.
- Patients were divided into two groups: one receiving carvedilol plus standard treatment, and a control group receiving only standard therapy.
- Transmitral filling parameters (E wave, A wave, E/A ratio, deceleration time, isovolumetric relaxation time) were assessed using echo Doppler methods.
Main Results:
- Carvedilol treatment led to significant improvements in diastolic parameters, including increased A wave, deceleration time, and isovolumetric relaxation time, with a reduced E/A ratio after 4 months.
- These diastolic improvements were sustained and even further ameliorated at 12 months, with observed reduction in E wave.
- After 1 year, the carvedilol group showed reduced LV volumes, decreased pulmonary pressure, and increased ejection fraction (EF), with Doppler modifications minimally related to heart rate and blood pressure.
Conclusions:
- Carvedilol effectively improves diastolic function in CHF patients with severe diastolic impairment, shifting filling patterns towards less restrictive states.
- These beneficial effects on diastolic function are observed early and persist for at least one year.
- The improvements in diastolic function induced by carvedilol appear to precede and potentially contribute to enhanced systolic function and hemodynamic status in CHF.
Aim:
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.
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