Long-term effects of iron deficiency in patients with heart failure with or without anemia: the RAID-HF follow-up study.

INTRODUCTION: Iron deficiency (ID) has been recognized as a relevant comorbidity in heart failure with reduced ejection fraction (HFrEF); however, study data have shown that diagnostic and therapeutic efforts on ID are primarily performed in patients with anemia. METHODS: The RAID-HF registry investigated consecutive patients with ID and HFrEF in 11 heart centers in Germany and Switzerland. The present analysis focuses on 1-year follow-up data in patients with versus without anemia. RESULTS: In 505 patients with HFrEF and ID and 418 patients with HFrEF without ID 1-year follow-up was performed. Patients with ID had a higher long-term mortality compared to those without ID (19.5% vs. 13.7%, p = 0.02) and reported a lower quality of life. Only a minority of patients with ID (9.3%) received iron supplementation during long-term course, just 4.7% intravenously. Anemia was associated with an elevated mortality whereas ID versus no ID did not predict mortality in anemic patients (log-rank p = 0.78). However, in patients without anemia ID versus no ID predicted mortality (log-rank p = 0.002). In the adjusted analysis a significant interaction remained, with ID being a significant predictor of 1-year mortality in patients without anemia (HR 2.15, 95% CI 1.12-3.78), but not in anemic patients (HR 0.99, 95% CI 0.65-1.49). CONCLUSIONS: RAID-HF demonstrates the impact of ID on long-term mortality and quality of life in patients with HFrEF and reveals an underuse of iron supplementation in current clinical practice. Particularly in patients without anemia the diagnosis of ID is of clinical relevance to identify patients at higher mortality risk.

Effects of 1-year treatment with highly purified omega-3 fatty acids on depression after myocardial infarction: results from the OMEGA trial.

OBJECTIVE: The effects of supplementation of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on prevalence and severity of depression were evaluated in patients after a myocardial infarction. METHOD: A cross-sectional evaluation (posttest-only design) within the prospective, randomized, controlled, multicenter OMEGA trial was performed in patients after myocardial infarction at 12 months' follow-up (N = 2,081; age, mean = 64 years; men, 76.7%; women, 21.8%) from April 2005 to June 2007. Patients received supplementation with ethyl esters 90 (460-mg EPA and 380-mg DHA) or placebo for 12 months. Depression was assessed with the Beck Depression Inventory-II (BDI-II); a BDI-II cutoff score of ≥ 14 was used as diagnosis of depression. RESULTS: When the total population was evaluated, no effects of EPA/DHA supplementation on depressive symptoms according to BDI-II score (mean [SD]) could be demonstrated: EPA/DHA (n = 1,046), 7.1 (6.9); placebo (n = 1,035), 7.1 (7.0); P = .7. The post hoc analyses of depressed patients with and without antidepressants revealed a tendency toward an antidepressant effect in patients with EPA/DHA supplementation as monotherapy: EPA/DHA (n = 125), 19.4 (5.8); placebo (n = 113), 19.9 (5.1); P = .07. However, in depressed patients with EPA/DHA supplementation as adjunctive to conventional antidepressants, a clinically relevant antidepressant effect was demonstrated: EPA/DHA (n = 33), 20.9 (7.1); placebo (n = 29), 24.9 (8.5); P < .05. CONCLUSIONS: EPA/DHA supplementation in the total sample of patients after myocardial infarction had no effect on depressive symptoms. The clinically relevant antidepressant effect in the subgroup of depressed patients with EPA/DHA supplementation as adjunctive to conventional antidepressants that was revealed in the post hoc analysis might provide a basis for a controlled, prospective trial of omega-3 augmentation of antidepressants in patients after myocardial infarction. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00251134.

Usefulness of heart rate to predict one-year mortality in patients with atrial fibrillation and acute myocardial infarction (from the OMEGA trial).

In the setting of acute myocardial infarction and sinus rhythm, the heart rate (HR) has been demonstrated to correlate closely with mortality. In patients presenting with acute myocardial infarction and atrial fibrillation (AF) on admission, however, the prognostic relevance of the HR has not yet been systematically addressed. A post hoc subgroup analysis of the data from the OMEGA trial was conducted to analyze whether the admission HR determines the 1-year mortality in patients presenting with AF in the setting of acute myocardial infarction. Of 3,851 patients enrolled in the OMEGA study, 211 (6%) presented with AF on admission. This subgroup was dichotomized according to the admission HR (cutoff 95 beats/min). Multiple regression analysis revealed that an admission HR of ≥95 beats/min independently determined the 1-year mortality in patients with AF (odds ratio 4.69, 95% confidence interval 1.47 to 15.01; p = 0.01). In conclusion, this is the first study demonstrating that a high HR (≥95 beats/min) on admission in patients with AF and acute myocardial infarction is associated with an almost fivefold mortality risk.

The effects of supplementation with omega-3 polyunsaturated Fatty acids on cardiac rhythm: anti-arrhythmic, pro-arrhythmic, both or neither? It depends .

Supplementation of omega-3 fatty acids (Ω-3) has been associated with a decreased cardiovascular risk, thereby concentrating attention on a potentially preventive effect regarding tachyarrhythmias and sudden cardiac death. However, recent randomized controlled trials challenge the efficacy of the additional application of Ω-3 and its anti-arrhythmic effect under certain clinical conditions. The present paper reflects the results of earlier and recent clinical studies with respect to the individual background conditions that may determine the clinical outcome of Ω-3 supplementation and thereby explain apparently conflicting clinical results. It is concluded that the efficacy of Ω-3 supplementation to prevent cardiac arrhythmias strongly depends on the underlying clinical and pharmacological conditions, a hypothesis that also is supported by data from experimental animal studies and by molecular interactions of Ω-3 at the cellular level.

OMEGA, a randomized, placebo-controlled trial to test the effect of highly purified omega-3 fatty acids on top of modern guideline-adjusted therapy after myocardial infarction.

BACKGROUND: There is no randomized, double-blind trial testing the prognostic effect of highly purified omega-3 fatty acids in addition to current guideline-adjusted treatment of acute myocardial infarction. METHODS AND RESULTS: OMEGA is a randomized, placebo-controlled, double-blind, multicenter trial testing the effects of omega-3-acid ethyl esters-90 (1 g/d for 1 year) on the rate of sudden cardiac death in survivors of acute myocardial infarction, if given in addition to current guideline-adjusted treatment. Secondary end points were total mortality and nonfatal clinical events. Patients (n=3851; female, 25.6%; mean age, 64.0 years) were randomized in 104 German centers 3 to 14 days after acute myocardial infarction from October 2003 until June 2007. Acute coronary angiography was performed in 93.8% and acute percutaneous coronary intervention in 77.8% of all patients. During a follow-up of 365 days, the event rates were (omega and control groups) as follows: sudden cardiac death, 1.5% and 1.5% (P=0.84); total mortality, 4.6% and 3.7% (P=0.18); major adverse cerebrovascular and cardiovascular events, 10.4% and 8.8% (P=0.1); and revascularization in survivors, 27.6% and 29.1% (P=0.34). CONCLUSIONS: Guideline-adjusted treatment of acute myocardial infarction results in a low rate of sudden cardiac death and other clinical events within 1 year of follow-up, which could not be shown to be further reduced by the application of omega-3 fatty acids. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00251134.

Highly purified omega-3 fatty acids for secondary prevention of sudden cardiac death after myocardial infarction-aims and methods of the OMEGA-study.

INTRODUCTION: During the last decades a large body of data has been accumulated indicating omega-3 fatty acids to exert beneficial effects on the prognosis of patients with cardiovascular disease. Especially, omega-3 fatty acids are regarded to be effective in reducing the risk of sudden cardiac death after acute myocardial infarction. However, treatment of acute myocardial infarction and secondary prevention considerably have been improved within the past years including early revascularization by PCI, the routine use of beta-blockers, statins and ACE-inhibitors as well as cardiac rehabilitation for improving life style measures. To date, there exists no controlled randomized trial testing the prognostic effect of omega-3 fatty acids after acute myocardial infarction in a double blind regimen under the conditions of modern treatment of myocardial infarction. MATERIALS AND METHODS: The present study therefore evaluates the effect of highly purified omega-3 fatty acid ethylesters (omega-3-acid ethyl esters 90=Zodin) on the rate of sudden cardiac death within 1 year after acute myocardial infarction. Secondary endpoints are total mortality, non-fatal cardiovascular events, rhythm abnormalities in holter monitoring and depression score. RESULT AND CONCLUSION: The recruitment-period started in October 2003 and is expected to last until December 2006. The results of the study are therefore expected for the beginning of 2008, when all patients will have completed the 12-months follow up-period.

[Non-contact mapping of the left atrium using a multi electrode mapping array]. / Non-Contact-Mapping des linken Vorhofs mittels Multielektroden-Ballonkatheter. Bedeutung der Katheterablation von Vorhofflimmern.

In contrast to the sequential mapping systems such as the conventional and the electroanatomic mapping, the non-contact mapping provides simultaneous mapping. The non-contact-mapping system detects far-field endocardial potentials from a multielectrode-array catheter and reconstructs over 3,000 unipolar virtual electrograms. Based on the virtual electrograms, the system produces an instantaneous three-dimensional (3-D) isopotential map. High-density mapping of the endocardial activation sequence allows immediate and simultaneous identification of a propagation vector along the line and the identification of an arrhythmogenic focus on a single beat. The methods and results of different ablation strategies for atrial fibrillation using the non-contact-mapping system are reported.

Noncontact mapping of ectopic atrial tachycardias: different characteristics of isopotential maps and unipolar electrogram.

The success rate for catheter ablation of ectopic atrial tachycardia (AT) has been limited by the inherent difficulty in localizing the site of origin within the complex three-dimensional structures of the atria. The objective of the study was to determine the usefulness of a noncontact mapping system for catheter ablation of AT. Radiofrequency ablation of 25 ATs was performed using a noncontact mapping system. Three different characteristics of isopotential maps and unipolar electrogram morphologies were observed: Group 1: Isopotential maps displayed a narrow, sharp ring of colors around a white, center spot. Unipolar electrograms revealed a Q-S morphology with a rapid dV/dt. Group 2: Isopotential maps displayed a broad ring of colors with little or no white spot in the center. Unipolar electrograms revealed a low amplitude, broad and smooth Q-S morphology in front of a second component with a rapid dV/dt. Group 3: Isopotential maps displayed a broad ring of colors. Unipolar electrogams revealed a low amplitude and fractionated waveform followed by endocardial breakthrough with a gradual dV/dt. Radiofrequency catheter ablation was successful in all ATs of groups 1 and 2, and failed in two of three ATs in group 3. The overall success rate was 92%. No severe complications were observed. Noncontact isopotential mapping is helpful to identify and characterize the origin of ectopic AT. Ablation success is associated with the characteristics of isopotential maps and unipolar electrogram morphologies. The overall success rate was 92%.

Catheter ablation of chronic atrial fibrillation with noncontact mapping: are continuous linear lesions associated with ablation success?

Catheter-based, right and left atrial compartmentalization procedure was evaluated using a noncontact mapping (NCM) system. Its usefulness to identify and close discontinuities in linear lesions in both atria was evaluated. The impact of linear lesion continuity on ablation success of chronic AF was also investigated. Nineteen patients with symptomatic, drug refractory chronic AF were studied. Right atrial ablation with three predefined lines was attempted in all patients. In 18 patients, left atrial ablation was performed with four linear lesions. During a follow-up of 12 +/- 3 months, 6 of 19 patients remained in sinus rhythm (SR) without antiarrhythmic agents (AAs). In addition, four patients were maintained in SR with AA. Thirteen of 14 patients with gaps identified during off-line analysis had recurrence of AF. Only one patient with a gap was free of recurrence without AAs. In the remaining five patients without recurrence of AF, no gap was observed during off-line analysis. In all four patients who were free of AF with additional treatment of AAs, two gaps had been identified. In the remaining nine patients with chronic AF recurrence, a mean of 4.9 gaps were identified. Excluding the initial learning period (first five patients) the success rate increased to 43% (6/14 patients) without and to 71% (10/14 patients) with AA. NCM identifies discontinuities in lines of ablation. Successful ablation of chronic AF is associated with continuity of linear lesions and good clinical technique demands a vigilant search for and closure of every gap.