Atrial fibrillation is associated with increased neurohumoral activation and reduced exercise tolerance in patients with non-ischemic dilated cardiomyopathy.

OBJECTIVES: To assess atrial fibrillation (AF) associated differences in proinflammatory cytokines, natriuretic peptide levels and exercise capacity in patients with heart failure (HF) secondary to non-ischemic dilated cardiomyopathy (NIDC). METHODS: We studied 147 NIDC patients, mean age 58.3+/-12.5 years, left ventricular (LV) ejection fraction 27.8+/-10.9% and NYHA class II-III. Neurohumoral activation was assessed by measurement of interleukin IL-1, IL-6, tumor necrosis factor-a (TNF-a), its soluble receptors sTNFR I and II, N-terminal atrial (NT-ANP) and -brain (NT-BNP) natriuretic peptide levels, and functional class was assessed by cardiopulmonary exercise test. RESULTS: Forty patients (27.5%) had chronic AF and they did not differ in age, LV ejection fraction or HF duration compared to patients in sinus rhythm (SR). AF was associated with increased levels of IL-6 (p=0.001), TNF-a (p=0.002), sTNFRI (p=0.023), NT-ANP (p<0.001) and NT-BNP (p=0.003), decreased exercise duration (p<0.001) and slightly reduced maximal oxygen consumption at peak exercise (p=0.07) compared to SR patients. No significant differences in cytokine and natriuretic peptide levels or exercise tolerance were noted when patients in AF were compared to the subgroup of SR with restrictive LV filling pattern. Multivariate analysis showed that NT-ANP (p=0.003) and IL-6 (p=0.006) plasma levels were independently associated with the presence of AF in our patient population. CONCLUSION: AF is associated with increased inflammatory state, natriuretic peptide levels and reduced exercise capacity in patients with HF secondary to NIDC. These findings suggest that the presence of AF in HF represents a more advanced stage of the syndrome.

Comparative efficacy of nebivolol versus carvedilol on left ventricular function and exercise capacity in patients with nonischemic dilated cardiomyopathy. A 12-month study.

PURPOSE: To compare the efficacy of nebivolol versus carvedilol on left ventricular (LV) function and exercise capacity in patients with nonischemic dilated cardiomyopathy (NIDC). METHODS: After enrollment in this double-blind trial, 72 patients, aged 55 +/- 9.5 years, with NIDC, LV ejection fraction (LVEF) < 45%, New York Heart Association classes II to III, were randomized to either nebivolol (34 patients) or carvedilol (38 patients) and were evaluated through echocardiography and exercise tests at baseline and 3 and 12 months after treatment. RESULTS: During follow-up, 4 patients discontinued nebivolol, although 3 patients stopped carvedilol. Patients in both the nebivolol and carvedilol groups showed a steady improvement in New York Heart Association class (P = .002 and < .001, at 12 months, respectively) and LVEF (P = .001 and < .001, at 12 months, respectively) that became significant from 3-month follow-up on. Intergroup analysis showed that carvedilol group had a greater increase in LVEF at 3 (P = .04) and 12 (P = .02) months' follow-up compared with nebivolol group. Advanced diastolic dysfunction regressed to earlier stages in carvedilol patients after 3 (P = .02) and 12 (P = .01) months' treatment, whereas in the nebivolol group, a significant improvement in diastolic dysfunction was found at the 12 months' follow-up (P = .02). Exercise duration improved in both groups at 12 months' follow-up (both P = .01), but in the nebivolol group, there was an initial deterioration at 3 months (P = .07). CONCLUSIONS: Both nebivolol and carvedilol appear relatively safe, with beneficial effects on LV systolic and diastolic function as well as exercise capacity in patients with NIDC after 12 months' treatment. However, carvedilol exhibits more favorable effects on LV function than does nebivolol.

Association of impaired glucose tolerance with increased heart rate and subclinical inflammation.

INTRODUCTION: This study was designed to assess possible alterations in heart rate (HR), heart rate variability (HRV) and circulating serum levels of proinflammatory cytokines in patients with impaired glucose tolerance (IGT). METHODS: Forty-five patients, aged 34-68 years, with IGT were compared with 28 age-matched healthy controls. Using a 24-hour ambulatory electrocardiogram, we calculated mean HR during daytime (HR-D), night-time (HR-N) and the entire 24-hour period (HR-24h), as well as time domain HRV parameters. From blood samples interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-a) and its soluble receptor (sTNFRII) were also calculated by immunoassay. RESULTS: Patients showed higher mean HR compared to controls and significantly elevated circulating levels of TNF-a, sTNFRII, and IL-6. Pearson correlation analysis showed that TNF-a was positively correlated with mean HR-D (r: 0.304, p=0.042). IL-6 was also positively correlated with mean HR-24h (r: 0.299, p=0.046) and with mean HR-D (r: 0.410, p=0.005). CONCLUSION: IGT patients have an increased HR and elevated cytokine levels. These changes could serve as an index of the primary atherosclerotic process.

Restrictive filling pattern is associated with increased humoral activation and impaired exercise capacity in dilated cardiomyopathy.

OBJECTIVES: Although heart failure (HF) is characterized by increased proinflammatory cytokines, natriuretic peptide levels and impaired exercise capacity, the effect of concomitant diastolic dysfunction on those parameters has not been adequately studied. METHODS: We analyzed circulating levels of IL-1, IL-6, TNF-alpha and its soluble receptors, sTNFRI and sTNFRII, Nt-ANP and Nt-BNP natriuretic peptides in 81 patients, aged 56+/-12 years, with non-ischemic dilated cardiomyopathy (NIDC), LVEF 29.7+/-7.75% and functional NYHA class II-III. An echocardiographic study and cardiopulmonary exercise test (CPE) were performed in all patients. RESULTS: Patients were divided into restrictive (24 patients, group I) and non-restrictive (57 patients, group II) groups, according to their transmitral-filling pattern. No differences in LV dimensions or LVEF were found between the two groups. Group I showed increased levels of IL-6 (P=0.006), TNF-alpha (P=0.05), sTNFRII (P=0.02), Nt-ANP (P<0.001) and Nt-BNP (P<0.001) and decreased exercise duration (P<0.001) and PVO(2) (P<0.001) compared to group II. The strongest independent predictors for restrictive filling pattern were Nt-ANP and IL-6 levels, while Nt-BNP levels were the strongest PVO(2) predictor. CONCLUSIONS: Restrictive filling pattern implying greater diastolic dysfunction may contribute to increased cytokine production in the heart failure syndrome, as well as greater increases in natriuretic peptides and decreased exercise tolerance.

Value of Doppler index combining systolic and diastolic myocardial performance in predicting cardiopulmonary exercise capacity in patients with congestive heart failure: effects of dobutamine.

STUDY OBJECTIVE: Doppler-derived myocardial performance index (MPI), a measure of combined systolic and diastolic myocardial performance, was assessed at rest and after low-dose dobutamine administration in patients with idiopathic or ischemic dilated cardiomyopathy. MPI also was correlated with other conventional echocardiographic indexes of left ventricular (LV) function, and its ability to assess cardiopulmonary exercise capacity in those patients was investigated. SETTINGS: A tertiary-care, university heart failure clinic. PATIENTS: Forty-two consecutive patients (27 men; mean [+/- SD] age, 57 +/- 10 years) with heart failure (New York Heart Association [NYHA] class, II to IV) who had received echocardiographic diagnoses of dilated cardiomyopathy. Coronary angiography distinguished the cause of dilated cardiomyopathy. INTERVENTIONS: Low-dose IV dobutamine was infused after patients underwent a baseline echocardiographic study. All patients also underwent a cardiopulmonary exercise test using a modified Naughton protocol. RESULTS: Advanced NYHA class and restrictive LV filling pattern were associated with higher index values. A negative correlation was found between MPI and LV stroke volume, cardiac output, early filling/late filling velocity ratio, and late LV filling velocity, as well as oxygen uptake at peak exercise (r = -0.550; p < 0.001) and at the anaerobic threshold (r = -0.490; p = 0.002). Dobutamine administration produced an improvement in MPI, reducing its value and decreasing the isovolumic relaxation and contraction times. Stepwise regression analysis revealed that the rest index and the late LV filling velocity were the only independent predictors of cardiopulmonary exercise capacity. CONCLUSION: MPI correlates inversely with LV performance, reflects disease severity, and is a useful complimentary variable in the assessment of cardiopulmonary exercise performance in patients with heart failure.