Effects of carvedilol on plasma B-type natriuretic peptide concentration and symptoms in patients with heart failure and preserved ejection fraction

doi:10.1016/j.amjcard.2004.05.004

The American Journal of Cardiology

Volume 94, Issue 4, 15 August 2004, Pages 448-453

https://doi.org/10.1016/j.amjcard.2004.05.004 Get rights and content

Abstract

Although the benefits of carvedilol in patients with heart failure and depressed ejection fraction (EF) have been elucidated, those in patients with preserved EF are not understood. We enrolled 40 patients with mild or moderate heart failure and EF ≥45%. They were randomly assigned to carvedilol (n = 19) or conventional therapy (n = 21). After 12 months of treatment, carvedilol significantly improved all end points (plasma concentration of B-type natriuretic peptide [BNP] from 175 (35 to 209) to 106 (52 to 160) pg/ml, mean (95% confidence interval) p <0.01; New York Heart Association functional class from 2.37 (2.13 to 2.61) to 1.56 (1.21 to 1.91), p <0.01; exercise capacity estimated with the Specific Activity Scale from 4.75 (4.50 to 5.00) to 5.68 (5.22 to 6.14) METs, p <0.02), whereas conventional therapy did not (plasma BNP concentration from 150 (114 to 186) to 174 (100 to 248) pg/ml; New York Heart Association functional class from 2.29 (2.08 to 2.50) to 2.11 (1.73 to 2.49); exercise capacity from 4.57 (4.34 to 4.80) to 4.72 (4.41 to 5.03) METs). Univariate regression analyses showed that only the use of carvedilol was correlated with the decrease in plasma BNP concentration (p <0.03). Multivariate analyses demonstrated that an ischemic cause of heart failure (p <0.02), high plasma concentration of BNP (p <0.02), left ventricular dilation (p <0.03), and use of carvedilol (p <0.04) at baseline were predictive of a decrease in plasma concentration of BNP. In conclusion, carvedilol potentially decreased neurohumoral activation, decreased symptoms, and increased exercise capacity in patients with heart failure and preserved EF.

Section snippets

Patients

We initially enrolled 48 consecutive outpatients referred to our heart failure clinic at Nagoya City University Hospital from April 1, 2000 to March 31, 2001, due to heart failure according to New York Heart Association (NYHA) functional class II or III and stage C of American College of Cardiology/American Heart Association guidelines for the evaluation and management of chronic heart failure in the adult.6 All patients met Framingham criteria for diagnosis of heart failure. LVEF, as assessed

Patient characteristics

There was no significant difference in baseline characteristics and treatment of patients between groups as listed in Table 1. Mean dosage of carvedilol at the end of the study was 10.9 mg/day (10.0, 77 to 14.0). Each patient using an angiotensin-converting enzyme inhibitor received 5 mg/day of enalapril. No patient received >80 mg/day of furosemide or >16 mg/day of torsemide. We administered 80 mg/day of valsartan to 2 patients on conventional therapy in whom treatment had failed.

Treatment failure and tolerability

Treatment

Discussion

In the present study, the addition of carvedilol to conventional therapy for 12 months decreased plasma BNP concentrations, alleviated symptoms, and increased exercise capacity in patients with heart failure and LVEF ≥45%. Treatment with carvedilol was tolerated as well as conventional therapy. Effects of β-adrenergic blockers in patients with preserved EF have not been tested in randomized trials except for the Swedish Evaluation of Diastolic Dysfunction in Congestive Heart Failure (SWEDIC),

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Heart failure with preserved ejection fraction (HFpEF) is a heterogenous disorder and tends to be predominant in elderly, female, and obese patients. HFpEF has been classified using various cut-offs of left ventricular ejection fraction in the published studies with a current cut-off of ≥50%. The evidence of beta-blocker therapy in HFpEF patients showed conflicting findings with variably reported efficacy. This review aims to examine the published studies on the use of beta blockers for the treatment of patients with HFpEF.
Diastolic dysfunction in hypertension
2017, Hipertension y Riesgo Vascular
Hypertension and coronary heart disease, often coexisting, are the most common risk factors for heart failure. The progression of hypertensive heart disease involves myocardial fibrosis and alterations in the left ventricular geometry that precede the functional change, initially asymptomatic. The left ventricular diastolic dysfunction is part of this continuum being defined by the presence of left ventricular diastolic dysfunction without signs or symptoms of heart failure or poor left ventricular systolic function. It is highly prevalent in hypertensive patients and is associated with increased cardiovascular morbidity and mortality. Despite its growing importance in clinical practice it remains poorly understood. This review aims to present the epidemiological fundamentals and the latest developments in the pathophysiology, diagnosis and treatment of left ventricular diastolic dysfunction.
La hipertensión y la enfermedad coronaria, a menudo coexistentes, son los factores de riesgo más comunes para la insuficiencia cardíaca. La progresión de la enfermedad cardíaca hipertensiva implica fibrosis miocárdica y alteraciones en la geometría ventricular izquierda que preceden al cambio funcional, inicialmente asintomático. La disfunción diastólica ventricular izquierda es parte de este proceso y se define como la presencia de disfunción diastólica del ventrículo izquierdo sin signos ni síntomas de insuficiencia cardíaca o mala función sistólica ventricular izquierda. Es altamente prevalente en pacientes hipertensos y se asocia con un aumento de la morbimortalidad cardiovascular. A pesar de su creciente importancia en la práctica clínica, el conocimiento de la disfunción diastólica del ventrículo izquierdo sigue siendo escaso. Esta revisión tiene como objetivo presentar los fundamentos epidemiológicos y los últimos avances en la fisiopatología, el diagnóstico y el tratamiento de la disfunción diastólica del ventrículo izquierdo.
Biologic variability of soluble ST2 in patients with stable chronic heart failure and implications for monitoring
2016, American Journal of Cardiology
Citation Excerpt :
The implications of these results are clear, especially when taken in conjunction with previously reported data. Studies have shown that standard heart failure therapies reduce average NTproBNP and BNP by up to 50%,12–16 whereas reductions in sST2 >50% have been shown to be indicative of therapeutic success of heart failure therapy.17 Thus, based on the results obtained in this study, a reduction of 50% in NTproBNP cannot be attributed to a therapeutic intervention alone as this reduction is less than the RCV.
Soluble ST2 (sST2) is a novel biomarker implicated in myocardial remodeling and fibrosis. Recent studies in normal subjects have suggested that the biologic variability (BV) of sST2 is significantly lower than that of the B-type natriuretic peptides and N-terminal pro B-type natriuretic peptide (NTproBNP). It may, consequently, be a better biomarker for monitoring patients with chronic heart failure (CHF). To date, no published studies have examined the BV of sST2 in a heart failure population. Blood samples from 50 outpatients with pharmacologically optimized stable CHF and persistent left ventricular dysfunction (ejection fraction <40%) were collected at baseline, 1 hour, 1 month, 3 months, and 6 months. Using log-transformed data, mean intra-individual coefficients of variation (CV_I) and subsequent reference change values were calculated for both NTproBNP and sST2. Results demonstrate significantly lower CV_I and reference change values for sST2 compared with NTproBNP at 1 month (12.02 [36%] vs 36.75 [103%]), p <0.001, 3 months (12.23 [36%] vs 40.98 [114%]), p <0.001, and 6 months (16.41 [47%] vs 46.02 [128%]), p <0.001. In conclusion, the BV of sST2 is significantly lower than that of NTproBNP in patients with CHF. These results support previous indications that sST2 may be a better biomarker for monitoring such patients.
Biological variation of galectin-3 and soluble ST2 for chronic heart failure: Implication on interpretation of test results
2013, American Heart Journal
Galectin-3 and soluble ST2 (sST2) are novel serum biomarkers of chronic heart failure.
The biological variability of galectin-3 and sST2 was measured from a cohort of 17 healthy subjects where blood was taken once every 2 weeks for 8 weeks (n = 4 samples) and from 12 subjects where blood was taken hourly (for galectin-3 only). The analytical, intraindividual, and interindividual variation were measured for galectin-3 (BG Medicine, Waltham, MA) and sST2 (Critical Diagnostics, San Diego, CA). From these measurements, the reference change (RCV) and index of individuality was 39% (hourly) and 61% (weekly) and 1.0 (hourly and weekly) for galectin-3. Corresponding RCV and index of individuality values for sST2 were 30% and 0.25.
The RCV result for sST2 was lower than the corresponding results for galectin-3, B-type natriuretic peptide, and N-terminal pro–B-type natriuretic peptide. These data suggest that sST2 may be more useful for monitoring long-term heart failure, and galectin-3 may be more useful for the diagnosis of heart failure remodeling.
Treatment of diastolic dysfunction in hypertension
2012, Nutrition, Metabolism and Cardiovascular Diseases
Citation Excerpt :
At 32 months, patients receiving propranolol had a 35% reduction in total mortality and a 37% reduction in the composite of total mortality or nonfatal myocardial infarction. The second trial showing the benefit of beta blockade in DHF consisted of 40 patients with mild or moderate heart failure and EF > 45% [30]. At 1 year, carvedilol improved New York Heart Association functional class from 2.37 to 1.56 (p < 0.01) and increased exercise capacity.
Diastolic dysfunction is present in half of patients with hypertension and has been shown to be associated with increased cardiovascular morbidity and mortality, as well as the development of heart failure. With the high prevalence of hypertension and its associated complications, treatment of diastolic dysfunction in hypertension is an important and desirable goal. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers have been shown to be effective in improvement of measures of diastolic function and are recommended as first-line agents in the control of hypertension in patients with diastolic heart failure. Beta-blockers, calcium channel blockers, and diuretics have also shown some efficacy in improved indices of diastolic filling. However, the independent impact of these pharmacologic interventions on prognosis and outcome in diastolic dysfunction has yet to be clarified. The Irbesartan in Heart Failure with Preserved Ejection Fraction (I-PRESERVE) study, Candesartan in Heart Failure: Assessment in Reduction of Mortality and Morbidity (CHARM-Preserved) trial and the Losartan Intervention For End-point Reduction in Hypertension (LIFE) Study all failed to show improved morbidity and mortality with these drugs although, the LIFE study showed reduced heart failure hospitalization in hypertensive patients with normal in-treatment diastolic function. The Trial Of Preserved Cardiac function heart failure with an Aldosterone anTagonist (TOPCAT) is an on-going large, international study evaluating the effect of spironolactone on cardiovascular mortality, aborted cardiac arrest, or hospitalization for diastolic heart failure. This and other studies will provide further insight into the pathophysiology and management of patients with diastolic dysfunction.
Effect of beta blockade on natriuretic peptides and copeptin in elderly patients with heart failure and preserved or reduced ejection fraction: Results from the CIBIS-ELD trial
2012, Clinical Biochemistry
Citation Excerpt :
Serial measurements of natriuretic peptides may be useful for monitoring and titration of HF treatment therapy [7]. While the effects of BB on natriuretic peptides have been reported in HFREF [8–13], there were only 2 randomized trials in HFPEF patients [14,15]. The reported responses are widely divergent, presumably reflecting differences between specific BBs and the effects of dose and duration of treatment and clinical state.
We sought to investigate the effect of beta-blocker (BB) up-titration on serum levels of NT-proBNP and copeptin in patients with heart failure (HF) with reduced (HFREF) or preserved ejection fraction (HFPEF).
Serial measurements of NT-proBNP and copeptin were obtained after initiation of BB up-titration in 219 elderly patients with HFREF or HFPEF.
After initial increasing trend of NT-proBNP at 6 weeks in HFREF patients, there was a subsequent decrease at 12 weeks of BB treatment up-titration (p = 0.003), while no difference was found compared to baseline levels. In contrast to NT-proBNP, there was a continuous decreasing trend of copeptin in HFREF patients (at 12 weeks: p = 0.026). In HFPEF patients, NT-proBNP significantly decreased (p = 0.043) compared to copeptin after 12 weeks of BB up-titration.
After 12 weeks of BB optimization copeptin might reflect successful up-titration faster than NT-proBNP in HFREF, while the opposite was found in patients with HFPEF.

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Effects of carvedilol on plasma B-type natriuretic peptide concentration and symptoms in patients with heart failure and preserved ejection fraction

Abstract

Section snippets

Patients

Patient characteristics

Treatment failure and tolerability

Discussion

Am J Cardiol

Am J Cardiol

Am J Cardiol

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J Am Coll Cardiol

J Am Coll Cardiol

Am Heart J

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Am J Cardiol

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J Card Fail