van den Maarten Berg

Heart failure and atrial fibrillation: current concepts and controversies.

Heart failure and atrial fibrillation are very common, particularly in the elderly. Owing to common risk factors both disorders are often present in the same patient. In addition, there is increasing evidence of a complex, reciprocal relation between heart failure and atrial fibrillation. Thus heart failure may cause atrial fibrillation, with electromechanical feedback and neurohumoral activation playing an important mediating role. In addition, atrial fibrillation may promote heart failure; in particular, when there is an uncontrolled ventricular rate, tachycardiomyopathy may develop and thereby heart failure. Eventually, a vicious circle between heart failure and atrial fibrillation may form, in which neurohumoral activation and subtle derangement of rate control are involved. Treatment should aim at unloading of the heart, adequate control of ventricular rate, and correction of neurohumoral activation. Angiotensin converting enzyme inhibitors may help to achieve these goals. Treatment should also include an attempt to restore sinus rhythm through electrical cardioversion, though appropriate timing of cardioversion is difficult. His bundle ablation may be used to achieve adequate rate control in drug refractory cases.

The Effect of Rate Control on Quality of Life in Patients With Permanent Atrial Fibrillation Data From the RACE II (Rate Control Efficacy in Permanent Atrial Fibrillation II) Study

OBJECTIVES The aim of this study was to investigate the influence of rate control on quality of life (QOL). BACKGROUND The RACE II (Rate Control Efficacy in Permanent Atrial Fibrillation II) trial showed that lenient rate control is not inferior to strict rate control in terms of cardiovascular morbidity and mortality. The influence of stringency of rate control on QOL is unknown. METHODS In RACE II, a total of 614 patients with permanent atrial fibrillation (AF) were randomized to lenient (resting heart rate [HR] <110 beats/min) or strict (resting HR <80 beats/min, HR during moderate exercise <110 beats/min) rate control. QOL was assessed in 437 patients using the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) questionnaire, AF severity scale, and Multidimensional Fatigue Inventory-20 (MFI-20) at baseline, 1 year, and end of study. QOL changes were related to patient characteristics. RESULTS Median follow-up was 3 years. Mean age was 68 ± 8 years, and 66% were males. At the end of follow-up, all SF-36 subscales were comparable between both groups. The AF severity scale was similar at baseline and end of study. At baseline and at end of study there were no differences in the MFI-20 subscales between the 2 groups. Symptoms at baseline, younger age, and less severe underlying disease, rather than assigned therapy or heart rate, were associated with QOL improvements. Female sex and cardiovascular endpoints during the study were associated with worsening of QOL. CONCLUSIONS Stringency of heart rate control does not influence QOL. Instead, symptoms, sex, age, and severity of the underlying disease influence QOL. (Rate Control Efficacy in Permanent Atrial Fibrillation; NCT00392613).

Critical appraisal of the revised Ghent criteria for diagnosis of Marfan syndrome

Radonic T, de Witte P, Groenink M, de Bruin‐Bon RACM, Timmermans J, Scholte AJH, van den Berg MP, Baars MJH, van Tintelen JP, Kempers M, Zwinderman AH, Mulder BJM. Critical appraisal of the revised Ghent criteria for diagnosis of Marfan syndrome.

Lack of prevention of heart failure by serial electrical cardioversion in patients with persistent atrial fibrillation

OBJECTIVE To investigate the occurrence of heart failure complications, and to identify variables that predict heart failure in patients with (recurrent) persistent atrial fibrillation, treated aggressively with serial electrical cardioversion and antiarrhythmic drugs to maintain sinus rhythm. DESIGN Non-randomised controlled trial; cohort; case series; mean (SD) follow up duration 3.4 (1.6) years. SETTING Tertiary care centre. SUBJECTS Consecutive sampling of 342 patients with persistent atrial fibrillation (defined as > 24 hours duration) considered eligible for electrical cardioversion. INTERVENTIONS Serial electrical cardioversions and serial antiarrhythmic drug treatment, after identification and treatment of underlying cardiovascular disease. MAIN OUTCOME MEASURES heart failure complications: development or progression of heart failure requiring the institution or addition of drug treatment, hospital admission, or death from heart failure. RESULTS Development or progression of heart failure occurred in 38 patients (11%), and 22 patients (6%) died from heart failure. These complications were related to the presence of coronary artery disease (p < 0.001, risk ratio 3.2, 95% confidence interval (CI) 1.6 to 6.5), rheumatic heart disease (p < 0.001, risk ratio 5.0, 95% CI 2.4 to 10.2), cardiomyopathy (p < 0.001, risk ratio 5.0, 95% CI 2.0 to 12.4), atrial fibrillation for < 3 months (p = 0.04, risk ratio 2.0, 95% CI 1.0 to 3.7), and poor exercise tolerance (New York Heart Association class III at inclusion, p < 0.001, risk ratio 3.5, 95% CI 1.9 to 6.7). No heart failure complications were observed in patients with lone atrial fibrillation. CONCLUSIONS Aggressive serial electrical cardioversion does not prevent heart failure complications in patients with persistent atrial fibrillation. These complications are predominantly observed in patients with more severe underlying cardiovascular disease. Randomised comparison with rate control treatment is needed to define the optimal treatment for persistent atrial fibrillation in relation to heart failure.

Cardiac assessment of patients with late stage Duchenne muscular dystrophy

Background. Duchenne muscular dystrophy (DMD) patients used to die mainly from pulmonary problems. However, as advances in respiratory care increase life expectancy, mortality due to cardiomyopathy rises. Echocardiography remains the standard diagnostic modality for cardiomyopathy in DMD patients, but is hampered by scoliosis and poor echocardiographic acoustic windows in adult DMD patients. Multigated cardiac radionuclide ventriculography (MUGA) does not suffer from these limitations. N-terminal proBNP (NTproBNP) has shown to be a diagnostic factor for heart failure. We present our initial experience with plasma NT-proBNP measurement in the routine screening and diagnosis of cardiomyopathy in adult mechanically ventilated DMD patients.Methods. Retrospective study, 13 patients. Echocardiography classified left ventricular (LV) function as preserved or depressed. NT-proBNP was determined using immunoassay. LV ejection fraction (LVEF) was determined using MUGA.Results. Median (range) NT-proBNP was 73 (25 to 463) ng/l. Six patients had an NT-proBNP >125 ng/l. Seven patients showed an LVEF <45% on MUGA. DMD patients with depressed LV function (n=4) as assessed by echocardiography had significantly higher median NT-proBNP than those (n=9) with preserved LV function: 346 (266 to 463) ng/l versus 69 (25 to 257) ng/l (p=0.003). NT-proBNP significantly correlated with depressed LV function on echocardiogram and with LVEF determined by MUGA.Conclusion. Although image quality of MUGA is superior to echocardiography, the combination of echocardiography and NT-proBNP achieves similar results in the evaluation of left ventricular function and is less time consuming and burdensome for our patients. We advise to add NT-proBNP to echocardiography in the routine cardiac assessment of DMD patients. (Neth Heart J 2009;17:232–7.)

N-terminal pro B-type natriuretic peptide levels predict newly detected atrial fibrillation in a population-based cohort

Background B-type natriuretic peptide (BNP) is secreted from cardiomyocytes and may reflect haemodynamic abnormalities predisposing to atrial fibrillation (AF). We aimed to investigate whether N-terminal pro BNP (NT-proBNP) is associated with newly detected AF in subjects obtained from the general population.Methods From the PREVEND programme (n=8592), we selected all subjects with an available baseline and four-year electrocardiogram and NTproBNP levels at baseline. We excluded subjects with AF at baseline and subjects with a serum creatinine >2.0 mg/dl.Results In total, 6494 subjects were eligible for the prospective analysis (aged 49±12 years, 49.7% men). At four years, AF was detected in 41 (0.6%) subjects. Median NT-proBNP levels at baseline in subjects with newly detected AF after four years was 62.2 (22.6 to 208.5) pg/ml as compared with 35.7 (15.9 to 68.7) pg/ml in those with sinus rhythm (p=0.001). Each 1 standard deviation increment in natural log transformed NT-proBNP was associated with a 54% (5% to 126%, p=0.028) increase in risk for AF after adjustment for other risk factors predisposing to AF. NT-proBNP levels above the sex-specific 80th percentile (97 pg/ml in women and 60 pg/ml in men) were associated with a multivariate odds ratio of 2.65 (1.22 to 5.76, p=0.01) for the occurrence of AF.Conclusion Plasma levels of NT-proBNP predict newly detected AF in subjects obtained from the general population independent of cardiovascular risk factors predisposing to AF. (Neth Heart J 2008;16:73-8.)

Role of the autonomic nervous system in vagal atrial fibrillation

Based on the seminal work of Coumel, the autonomic nervous system is considered to play a pathophysiological role in a subset of patients with atrial fibrillation (AF).1 In particular, Coumel put forward the concept of so-called vagal AF. Yet, the precise role of the autonomic nervous system in vagal AF is unclear. Is vagal AF caused by abnormal autonomic function or abnormal autonomic tone, or is there perhaps an increased sensitivity of the heart to vagal influences? In previous studies,2,3 both autonomic function and autonomic tone were shown to be normal in patients with AF, suggesting that increased sensitivity of the heart to vagal influences plays a role. However, these studies were limited by small sample size. In the present study we sought to collect additional data to define the role of the autonomic nervous system in vagal AF. The study group comprised 73 patients with paroxysmal AF. None of the patients had congestive heart failure. On average, patients had a three year history of one paroxysm per week lasting two hours. Patients were considered to have vagal AF if they met the following clinical criteria: (1) most attacks occurred at rest or during sleep, and generally terminated with exercise or in the morning; and (2) if available, typical electrocardiographic findings (preceding sinus bradycardia and a slow ventricular response during AF) were present. Ten patients fulfilled these clinical criteria (vagal AF group); eight men, mean (SD) age 59 (12) years. One patient had hypertension, one patient had mild aortic valve disease, and one patient had angina pectoris, but the other seven patients had lone AF. Mean left …

Diagnostic yield in adults screened at the marfan outpatient clinic using the 1996 and 2010 ghent nosologies

Marfan syndrome (MFS) is diagnosed according to the Ghent nosology, which has recently been revised. In the Netherlands, evaluation for possible MFS is performed in specialized Marfan outpatient clinics. We investigated the diagnostic yield in our clinic and the impact of the 2010 nosology. All adult patients (n = 343) who visited our clinic between 1998 and 2008 were included. We analyzed their reasons for referral, characteristics, and established diagnoses. In addition, we applied the 2010 nosology to all patients and compared the outcomes to those obtained with the 1996 nosology. Diagnoses that were made using the 1996 and the 2010 Ghent nosology included MFS (44/343 vs. 47/343), familial thoracic aortic aneurysm and/or dissection (22/343 vs. 22/343 patients), Loeys–Dietz syndrome (4/343 vs. 4/343 patients), and (familial) mitral valve prolapse (MVPS; 5/343 vs. 28/343 patients). In both nosologies, 77% of MFS patients had an FBN1 mutation. The 2010 nosology led to an increase in the number of diagnoses made: 4 additional cases of MFS were identified (one patient was “lost” who no longer fulfilled the criteria) and 23 additional cases of MVPS were diagnosed. The diagnostic yield of patients with aortic root dilatation was 65% using the 1996 nosology and 70% using the 2010 nosology. The change in diagnoses did not lead to a difference in clinical follow‐up. We conclude that the diagnostic yield of our specialized clinic was high, in particular in patients with aortic root dilatation. Further more the 2010 Ghent nosology led to a significant increase in the number of diagnoses made, mainly due to lowering of the diagnostic threshold for MVPS.

Acute Administration of Angiotensin Converting Enzyme Inhibitors in Thrombolysed Myocardial Infarction Patients Is Associated with a Decreased Incidence of Heart Failure, but an Increased Re-Infarction Risk

Introduction: Ventricular remodeling starts very early after the onset of an acute myocardial infarction (AMI), and can be prevented by ACE-inhibitors. However, very limited data are available on the effect of acute (< 9 hours) treatment with angiotensin converting enzyme (ACE) inhibitors after an AMI on mortality, heart failure and re-infarction. The aim of the present study was to evaluate the effects of acute ACE-inhibitor treatment.Methods: We performed a pooled analysis of three very similar randomized, placebo-controlled multi-center trials. In 845 thrombolysed patients with mainly first anterior MI, patients were randomised to acute ACE-inhibitor treatment (< 9 hours after MI) or placebo.Results: After acute ACE-inhibitor treatment we observed similar 3-months mortality rates, and a significant reduction in the incidence of 3-months heart failure (26.1 vs. 19.3%; RR 0.67; 95% CI 0.45–1.0) as compared to placebo. In contrast, acute ACE-inhibitor treatment was associated with a significant 2.0 times increased 3-months re-infarction risk (7.0 vs. 3.6%; RR 2.0; 95% CI 1.1 to 3.8). Subgroup-analysis showed that patients with small infarct sizes treated with acute ACE-inhibitor (peak CPK < 1000 IU) had a 7.6 times higher re-infarction risk (95% CI 1.7 to 33) than patients with small infarctions treated with placebo.Conclusions: Acute ACE-inhibitor treatment in thrombolysed patients with mainly first anterior AMI resulted in a reduction of heart failure and similar mortality, but an increase in re-infarction rates, especially in patients with small infarct sizes. These results warrant caution for the very early use of ACE-inhibitors in smaller infarctions, although this needs to be confirmed in a larger prospective randomised clinical trial.

Haplotype sharing test maps genes for familial cardiomyopathies

van der Zwaag PA, van Tintelen JP, Gerbens F, Jongbloed JDH, Boven LG, van der Smagt JJ, van der Roest WP, van Langen IM, Bikker H, Hauer RNW, van den Berg MP, Hofstra RMW, te Meerman GJ. Haplotype sharing test maps genes for familial cardiomyopathies.