Idiopathic dilated cardiomyopathy and chronic atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is common in idiopathic dilated cardiomyopathy (IDC). We explored the clinical characteristics of IDC patients with chronic AF compared with those with sinus rhythm (SR). METHODS: A group of patients with IDC underwent extensive non-invasive and invasive evaluation during a hospitalization period. The patients were further divided into two groups with AF (n = 19) and SR (n = 68). RESULTS: Left atrial diameter was greater (P<0·001), left ventricular end-diastolic diameter smaller (P<0·05), left ventricular end-diastolic and end-systolic volumes smaller (P<0·01 for all), mean pulmonary artery pressure and pulmonary capillary wedge pressure higher (P<0·05 for both), cardiac output and maximal oxygen consumption lower (P<0·01 and P<0·05, respectively), and the levels of N-terminal pro-brain natriuretic peptide and interleukin-6 higher (P<0·05 for both) in AF group compared with SR group. Left ventricular ejection fraction and left ventricular end-diastolic pressure were similar in both groups. CONCLUSIONS: In spite of otherwise more unfavourable prognostic factor profile, left ventricular size was observed to be smaller in chronic AF compared with SR in well-characterized patients with IDC. The confirmation and possible explainers of this paradoxical phenomenon need further studies in larger patient cohorts.

Intermittent levosimendan treatment in patients with severe congestive heart failure.

OBJECTIVE: Levosimendan (LS) is a novel inodilator for the treatment of severe congestive heart failure (CHF). In this study, we investigated the potential long-term effects of intermittent LS treatment on the pathophysiology of heart failure. METHODS: Thirteen patients with modest to severe CHF received three 24-h intravenous infusions of LS at 3-week intervals. Exercise capacity was determined by bicycle ergospirometry, well-being assessed by Minnesota Living with Heart Failure Questionnaire (MLHFQ) and laboratory parameters of interest measured before and after each treatment. RESULTS: One patient experienced non-sustained periods of ventricular tachycardia (VT) during the first infusion and had to discontinue the study. Otherwise the LS infusions were well tolerated. Exercise capacity (VO2max) did not improve significantly during the study although symptoms decreased (P < 0.0001). Levels of plasma NT-proANP, NT-proBNP and NT-proXNP decreased 30-50% during each infusion (P < 0.001 for all), but the changes disappeared within 3 weeks. Although norepinephrine (NE) appeared to increase during the first treatment (P = 0.019), no long-term changes were observed. CONCLUSION: Intermittent LS treatments decreased effectively and repetitively plasma vasoactive peptide levels, but no carryover effects were observed. Patients' symptoms decreased for the whole study period although there was no objective improvement of their exercise capacity. The prognostic significance of these effects needs to be further studied.

The activation of the inflammatory cytokines in overweight patients with mild obstructive sleep apnoea.

It is widely accepted that obstructive sleep apnoea (OSA) is linked with cardiovascular diseases. The relationship is complex and remains still poorly understood. The presence of chronic systemic inflammation has been connected with pathogenesis of both OSA and cardiovascular diseases. While atherogenesis is believed to be a process of many years, little is known about the potential impact of the largest OSA subgroup, mild OSA, on the development of cardiovascular diseases. The aim of the present study was to assess whether untreated mild OSA is associated with an activation of inflammatory cytokine system. The adult study population consisted of two groups: 84 patients with mild OSA [apnoea-hypopnoea index (AHI) 5-15 h(-1)] and 40 controls (AHI <5 h(-1)). Serum concentrations of pro- and anti-inflammatory cytokines were measured before any interventions. After adjustments for age, sex, body mass index, fat percentage, most important cardiometabolic and inflammatory diseases, and non-steroidal anti-inflammatory medication, the mean level of tumour necrosis factor-alpha was significantly elevated (1.54 versus 1.17 pg mL(-1), P = 0.004), whereas the level of interleukin-1 beta (IL-1 beta) was reduced (0.19 versus 0.23 pg mL(-1), P = 0.004) in patients with mild OSA compared with controls. The concentrations of the protective anti-inflammatory cytokines, interleukin-10 (1.28 versus 0.70 pg mL(-1), P < 0.001) and interleukin-1 receptor antagonist (478 versus 330 pg mL(-1), P = 0.003) were elevated in the OSA group. The concentrations of C-reactive protein increased, but IL-1 beta decreased along with the increase of AHI. Mild OSA was found to be associated not only with the activation of the pro-inflammatory, but also with the anti-inflammatory systems.

Clinical significance of troponin I efflux and troponin autoantibodies in patients with dilated cardiomyopathy.

BACKGROUND: The appearance of circulating autoantibodies against cardiac troponin I (cTnAbs) in patients with heart failure has been reported. We sought to evaluate the role of circulating cardiac troponin I (cTnI) and cTnAbs in the pathophysiology and prognosis of idiopathic dilated cardiomyopathy. METHODS AND RESULTS: Circulating concentrations of cTnI and the presence of cTnAbs were determined in 95 patients with idiopathic dilated cardiomyopathy. The patients underwent laboratory testing, echocardiography, cardiopulmonary exercise testing, gated single photon emission computed tomography, and both-sided cardiac catheterization during a 3-day study period. Compared with cTnI- patients, the hearts of cTnI+ patients (cTnI > or = 0.01 ng/mL, n = 19) were significantly more dilated (left ventricular end-diastolic diameter 67 vs 61 mm, P < .05; left ventricular end-systolic dimension, 55 vs 49 mm, P < .01; echocardiography) and demonstrated greater intracardiac volumes (left ventricular end-diastolic volume 161 vs 132 mL, P = .060; left ventricular end-systolic volume 112 vs 82 mL, P < .05; gated single photon emission computed tomography), more disturbed systolic (ejection fraction 27 vs 33%, P < .05; gated single photon emission computed tomography) and cardiac sympathetic (123I-metaiodobenzylguanidine washout: 41% vs 34%; P < .05) function, and higher levels of vasoactive peptides (N-terminal proatrial natriuretic peptide 1030 vs 558 pmol/L, P < .05; N-terminal pro-B type natriuretic peptide 337 vs 115 pmol/L, P < .05). In addition, during a median follow-up time of 4.1 years, cTnI+ patients had clinical end points (cardiovascular death, heart transplantation, or clinical need for an automatic implantable cardioverter defibrillator) more often than cTnI- patients (37% vs 8%, P < .01). The presence of circulating cTnAbs (n = 15) was not associated with patients' clinical status or outcome. CONCLUSION: Patients with idiopathic dilated cardiomyopathy with cTnI efflux demonstrate more prominent changes in the indices of left ventricular remodeling and function than patients without signs of cTnI efflux. Moreover, elevated serum cTnI is associated with poor clinical outcome. The presence of circulating cTnAbs seems to have less utility in the clinical assessment of these patients. However, their pathogenic role in disease progression in the long term cannot be excluded.

Prognostic role of pro- and anti-inflammatory cytokines and their polymorphisms in acute decompensated heart failure.

BACKGROUND: Cytokines play an important role in chronic heart failure (HF), but little is known about their involvement in acute decompensated heart failure (ADHF). AIM: To evaluate the prognostic role of inflammatory cytokines in patients with ADHF. METHODS: Levels of interleukin (IL)-6, tumour necrosis factor alpha (TNF-alpha), IL-10 and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured in 423 patients with ADHF. In addition, appropriate cytokine gene polymorphisms were determined. Survival was followed up to 12 months, and prognostic factors were evaluated. RESULTS: Elevated levels of IL-6 and TNF-alpha were strongly associated with increased 12-month mortality (P<0.001 for both), whereas the level of IL-10 was predictive only of 6-month mortality (P<0.01). In multivariate analysis IL-6, chronic renal insufficiency, NT-proBNP, age/10 years' increase and TNF-alpha were identified as the most powerful predictors of 12-month mortality. Furthermore, high levels of both IL-6 and NT-proBNP were associated with >7-fold mortality. Cytokine gene polymorphisms were not associated with outcome. CONCLUSIONS: Circulating levels of pro-inflammatory cytokines IL-6 and TNF-alpha, and the level of an anti-inflammatory cytokine IL-10, but not their gene polymorphisms, provide novel and important prognostic information in patients with ADHF. Combining measurements of pro-inflammatory cytokines and NT-proBNP seems a promising tool in the prognostic assessment of these patients.

Utility of plasma apelin and other indices of cardiac dysfunction in the clinical assessment of patients with dilated cardiomyopathy.

Apelin is a recently discovered peptide ligand reported to be involved in the regulation of cardiovascular homeostasis. The exact role of apelin in the pathophysiology of congestive heart failure has remained obscure, and the reported circulating levels of apelin in patients with heart failure have been contradictory. To establish the role of apelin in the assessment of cardiac dysfunction we measured plasma apelin levels in 65 patients with congestive heart failure caused by idiopathic dilated cardiomyopathy (IDC) and 14 healthy volunteers by specific radioimmunoassay. IDC patients were carefully examined including echocardiography, both-sided cardiac catheterization and cardiopulmonary exercise test. In addition, plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), N-terminal pro-atrial natriuretic peptide (NT-proANP), interleukin (IL)-6, tumor necrosis factor alpha (TNF-alpha), epinephrine and norepinephrine were determined. Plasma apelin levels were similar in IDC patients (median 26.5 pg/ml, range<3.40-97.6 pg/ml) and in control subjects (median 24.1 pg/ml, range 19.0-28.7 pg/ml; p=NS). Unlike the levels of NT-proBNP, IL-6, TNF-alpha, and norepinephrine, plasma apelin levels did not reflect the severity of heart failure. Our study demonstrates that although disturbed apelin-APJ signalling in heart may play a role in the pathophysiology of heart failure, circulating apelin levels cannot be applied in the clinical assessment of patients with chronic left ventricular dysfunction.