Alessandra Manerba

Effects of n-3 polyunsaturated fatty acids on left ventricular function and functional capacity in patients with dilated cardiomyopathy.

OBJECTIVES This study was designed to test the effects of n-3 polyunsaturated fatty acids (PUFAs) on left ventricular (LV) systolic function in chronic heart failure (HF) due to nonischemic dilated cardiomyopathy (NICM). BACKGROUND One hundred thirty-three patients with NICM and minimal symptoms on standard therapy were randomized to 2 g of n-3 PUFAs or placebo. LV function and functional capacity were assessed prospectively by echocardiography and cardiopulmonary exercise testing at baseline and at 12 months after randomization. METHODS Patients with chronic HF due to NICM and minimal symptoms while receiving evidence-based therapy were enrolled. LV function and functional capacity were assessed prospectively by echocardiography, cardiopulmonary exercise test, and New York Heart Association functional class at baseline and at 12 months after randomization to either 2 g of n-3 PUFAs or placebo. RESULTS At 12 months after randomization, the n-3 PUFAs group and the placebo group differed significantly (p <0.001) in regard to: 1) LV ejection fraction (increased by 10.4% and decreased by 5.0%, respectively); 2) peak VO(2) (increased by 6.2% and decreased by 4.5%, respectively); 3) exercise duration (increased by 7.5% and decreased by 4.8%, respectively); and 4) mean New York Heart Association functional class (decreased from 1.88 ± 0.33 to 1.61 ± 0.49 and increased from 1.83 ± 0.38 to 2.14 ± 0.65, respectively). The hospitalization rates for HF were 6% in the n-3 PUFAs and 30% in the placebo group (p = 0.0002). CONCLUSIONS In patients with NICM and minimal symptoms in response to evidence-based medical therapy, n-3 PUFAs treatment increases LV systolic function and functional capacity and may reduce hospitalizations for HF. Given these promising results, larger studies are in order to confirm our findings.

n-3 PUFAs and cardiovascular disease prevention

Today, there are several observational and experimental studies, especially clinical randomized trials, that have proven the beneficial effects of n-3 polyunsaturated fatty acids (PUFAs). The most compelling evidence for the cardiovascular benefits of n-3 PUFAs comes from studies of primary prevention in patients following myocardial infarction, and most recently, in patients with heart failure. In this review, we analyze the evidence from epidemiologic studies and from large randomized controlled trials showing the benefits of n-3 PUFAs, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in primary and secondary cardiovascular prevention. Further studies are needed to determine optimal dosing and the relative ratio of DHA and EPA that provide maximal cardioprotection.

Six-year prognosis of diabetic patients with coronary artery disease

Eur J Clin Invest 2012; 42 (4): 376–383

Effects of supplementation with polyunsaturated fatty acids in patients with heart failure

Despite the clinical and prognostic improvement obtained with the current medical treatment, heart failure (HF) continues to have high morbidity and mortality and its prevalence is increasing in most regions of the world. Thus, there is a need for novel adjunctive therapies that act independently of current neurohormonally and haemodynamically oriented drugs. Nutritional approaches are particularly attractive because they could work additively with established therapies without negative hemodynamic effects. There is growing evidence that omega-3 polyunsaturated fatty acids (n-3 PUFAs) supplementation positively impacts established pathophysiological mechanisms in HF and thus has a potential role for preventing and treating HF. The results of the GISSI-HF trial have indicated that, in patients with chronic HF on evidence-based therapy, long term treatment with PUFAs reduced mortality and hospitalizations for cardiovascular reasons, irrespective of etiology and left ventricular (LV) ejection fraction (EF). The purpose of this review is to summarize the evidence emerged from studies conducted so far on the effect of n-3 PUFAs in HF.

Endothelial damage due to air pollution

The first human deaths due to air pollution were recorded in the mid-20th century. There were 6,000 cases of illness recorded in Donora, Pennsylvania, in 1948 and 20,000 in London in 1952; 15 and 4,000 cases of death, respectively, were allegedly ascribed to air pollution. Since then, many countries have adopted standards of air quality in order to protect environmental and human health, although the quality of the air in some industrialized countries remains worrying. Emerging countries in the Far East and South America are also cause for concern because of the growth in the population, industrialization and transport (1). The WHO World Health Report 2002 estimated that air pollutants, particularly PM10, are associated with a mortality rate of 5% for cancer of the respiratory system, 2% for cardiovascular diseases and about 1% for respiratory tract infections. These estimates consider the mortality but not the morbidity rate, which would increase proportionally the number of cases of these pathologies, despite the difficulty in evaluation (2). ENVIRONMENTAL POLLUTANTS According to the Italian Presidential Decree no. 203 dated May 24th 1998, air pollution is defined as “any modification to the normal composition or to the physical state of the air, due to the presence of one or more substances in such quantities and characteristics as to alter its healthiness and the normal environmental conditions; this contamination can be directly or indirectly dangerous for human health and could jeopardize recreational and normal activities performed in the environment. Moreover, this could seriously affect biological resources, the ecosystem, and public and private tangible assets”. The thus-defined pollutants, which can be in gaseous, liquid or solid form, are commonly classified as either primary or secondary. Primary pollutants are released into the atmosphere directly by nature or as a consequence of human activity. Many of these pollutants, which have an elevated reactivity, either intrinsic or sunlight-induced, can combine easily or react with natural substances in the atmosphere, causing secondary pollutants. The main pollutants derive from: the combustion process in car engines, domestic heating and industrial equipment; wear and tear and the dispersion of materials, e.g. the road surface and car tires; certain manufacturing processes.

PROGNOSTIC ROLE OF ATRIAL FIBRILLATION AND HEART RATE CONTROL IN CHRONIC HEART FAILURE PATIENTS

methods: we performed a retrospective analysis of pts with reduced Left Ventricular Ejection Fraction (LVEF<45%) and stable clinical condition (neither events nor therapeutic changes in the previous 3 months) followed in our HF clinic. Demographic, clinical, echocardiographic and laboratory parameters were recorded. We considered as composite endpoint the occurrence of cardiovascular (CV) death and HF or CV hospitalization at 1 year follow-up. We analyzed clinical characteristics and events in sinus rhythm (SR) pts and in AF pts, stratified according to median baseline HR value (70 bpm).

n-3 Polyunsaturated Fatty Acids in the Prevention of Atrial Fibrillation Recurrences After Electrical Cardioversion

Background— n-3 polyunsaturated fatty acids (n-3 PUFAs) exert antiarrhythmic effects and reduce sudden cardiac death. However, their role in the prevention of atrial fibrillation remains controversial. We aimed to determine the effect of n-3 PUFAs in addition to amiodarone and a renin-angiotensin-aldosterone system inhibitor on the maintenance of sinus rhythm after direct current cardioversion in patients with persistent atrial fibrillation. Methods and Results— We conducted a randomized, double-blind, placebo-controlled, parallel-arm trial in patients with persistent atrial fibrillation, with at least 1 relapse after cardioversion, and treated with amiodarone and a renin-angiotensin-aldosterone system inhibitor. Participants were assigned to placebo or n-3 PUFAs 2 g/d and then underwent direct current cardioversion 4 weeks later. The primary end point was the probability of maintenance of sinus rhythm at 1 year after cardioversion. Of 254 screened patients, 199 were found to be eligible and randomized. At the 1-year follow up, the probability of maintenance of sinus rhythm was significantly higher in the n-3 PUFAs–treated patients compared with the placebo group (hazard ratio, 0.62 [95% confidence interval, 0.52 to 0.72] and 0.36 [95% confidence interval, 0.26 to 0.46], respectively; P=0.0001). Conclusions— In patients with persistent atrial fibrillation on amiodarone and a renin-angiotensin-aldosterone system inhibitor, the addition of n-3 PUFAs 2 g/d improves the probability of the maintenance of sinus rhythm after direct current cardioversion. Our data suggest that n-3 PUFAs may exert beneficial effects in the prevention of atrial fibrillation recurrence. Further studies are needed to confirm and expand our findings. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01198275.

n-3 Polyunsaturated Fatty Acids in the Prevention of Atrial Fibrillation Recurrences After Electrical CardioversionClinical Perspective

Background— n-3 polyunsaturated fatty acids (n-3 PUFAs) exert antiarrhythmic effects and reduce sudden cardiac death. However, their role in the prevention of atrial fibrillation remains controversial. We aimed to determine the effect of n-3 PUFAs in addition to amiodarone and a renin-angiotensin-aldosterone system inhibitor on the maintenance of sinus rhythm after direct current cardioversion in patients with persistent atrial fibrillation. Methods and Results— We conducted a randomized, double-blind, placebo-controlled, parallel-arm trial in patients with persistent atrial fibrillation, with at least 1 relapse after cardioversion, and treated with amiodarone and a renin-angiotensin-aldosterone system inhibitor. Participants were assigned to placebo or n-3 PUFAs 2 g/d and then underwent direct current cardioversion 4 weeks later. The primary end point was the probability of maintenance of sinus rhythm at 1 year after cardioversion. Of 254 screened patients, 199 were found to be eligible and randomized. At the 1-year follow up, the probability of maintenance of sinus rhythm was significantly higher in the n-3 PUFAs–treated patients compared with the placebo group (hazard ratio, 0.62 [95% confidence interval, 0.52 to 0.72] and 0.36 [95% confidence interval, 0.26 to 0.46], respectively; P=0.0001). Conclusions— In patients with persistent atrial fibrillation on amiodarone and a renin-angiotensin-aldosterone system inhibitor, the addition of n-3 PUFAs 2 g/d improves the probability of the maintenance of sinus rhythm after direct current cardioversion. Our data suggest that n-3 PUFAs may exert beneficial effects in the prevention of atrial fibrillation recurrence. Further studies are needed to confirm and expand our findings. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01198275.

Response to the Letter of Hester Den Ruijter and Ruben Coronel Regarding the Article "The Role of n-3 PUFAs in Preventing the Arrhythmic Risk in Patients with Idiopathic Dilated Cardiomyopathy"

We thank Drs Hester M. Den Ruijter and Ruben Coronel for their valuable comments [1]. Consumption of fish or fish oil is associated with lower risk of arrhythmic outcomes including sudden death and atrial fibrillation [2]. However, the mechanisms underlying these relationships are not well established and may include direct or indirect effects on myocardial electrophysiology, which may apply to numerous potential arrhythmogenic substrates (heart failure, acute ischemia, infarct scar and hibernated/ stunned myocardium). Of note, n-3 PUFAs may worsen arrhytmic events based on re-entry circuits activation as in the presence of large infarct scar or hibernated/stunned myocardium, but may also reduce risk of ventricular arrhythmias in implantable cardioverter defibrillator patients without coronary artery disease [3]. Trials evaluating fish oil have shown controversial results, possibly due to different sample size and duration of intake or variable pharmacological doses of fish oil, dietary intake of n-6 fatty acids and concomitant medication [4]. Different arrhythmogenic substrates may be a cause of divergent results, as well. In our patients, with idiopathic dilated cardiomyopathy, the predominant arrhythmogenic substrate is a nonreentrant mechanism that likely involves triggered activity from delayed after depolarizations in response to catecholamines. Recent work by Drs Den Ruijter and Coronel has shown that triggered arrhythmias are inhibited by fish oil in isolated myocytes of patients with end-stage heart failure as a result of cardiac action potential shortening, decreased diastolic and systolic intracellular calcium levels and a reduced response to β-adrenergic stimulation [5]. Probably in heart failure patients also other favorable biological effects of n-3 PUFAs, as we observed in our study (reduction of heart rate, inflammatory pathways and catecholamine plasma levels, increase of heart rate variability, etc), may indirectly contribute to antiarrhythmic result of the fish oil treatment. Certainly, as Dr Raitt has emphasized in his editorial, an improvement in markers of risk may not translate to improvement in outcome and large prospective trials assessing the n-3 PUFA effects on mortality or severe ventricular arrhythmias need to be performed [6]. We agree with Drs Den Ruijter and Coronel and hypothesize that habitual consumption of fish and longchain n-3 fatty acid intake would be associated with more favorable outcomes just in selected populations. According to the available evidence, trial designs in heart failure patients have to take into account not only the different Cardiovasc Drugs Ther (2009) 23:335–336 DOI 10.1007/s10557-009-6174-7

The Prevention of Sudden Death: New Perspectives

Sudden cardiac death (SCD) is unexpected natural death due to cardiac causes, and includes the abrupt loss of consciousness within 1 h from the onset of acute symptoms, with or without preexisting heart disease. It is very difficult to evaluate the exact incidence of SCD because the concept of “sudden events” has not been precisely defined [1].