Abstract Background Recent trials of fish oil for the prevention of atrial fibrillation (AF) recurrence have provided mixed results. Notable uncertainties in the existing evidence base include the ...roles of high-dose fish oil, inflammation, and oxidative stress in patients with paroxysmal or persistent AF not receiving conventional antiarrhythmic (AA) therapy. Objectives The aim of this study was to evaluate the influence of high-dose fish oil on AF recurrence, inflammation, and oxidative stress parameters. Methods We performed a double-blind, randomized, placebo-controlled, parallel-arm study in 337 patients with symptomatic paroxysmal or persistent AF within 6 months of enrollment. Patients were randomized to fish oil (4 g/day) or placebo and followed, on average, for 271 ± 129 days. Results The primary endpoint was time to first symptomatic or asymptomatic AF recurrence lasting >30 s. Secondary endpoints were high-sensitivity C-reactive protein (hs-CRP) and myeloperoxidase (MPO). The primary endpoint occurred in 64.1% of patients in the fish oil arm and 63.2% of patients in the placebo arm (hazard ratio: 1.10; 95% confidence interval: 0.84 to 1.45; p = 0.48). hs-CRP and MPO were within normal limits at baseline and decreased to a similar degree at 6 months (Δhs-CRP, 11% vs. −11%; ΔMPO, −5% vs. −9% for fish oil vs. placebo, respectively; p value for interaction = NS). Conclusions High-dose fish oil does not reduce AF recurrence in patients with a history of AF not receiving conventional AA therapy. Furthermore, fish oil does not reduce inflammation or oxidative stress markers in this population, which may explain its lack of efficacy. (Multi-center Study to Evaluate the Effect of N-3 Fatty Acids OMEGA-3 on Arrhythmia Recurrence in Atrial Fibrillation AFFORD; NCT01235130 ).
ABSTRACT BACKGROUND Comorbidity indexes derived from administrative databases are essential tools of research in global health. We sought to develop and validate a novel cardiac-specific comorbidity ...index, and to compare its accuracy with the generic Charlson–Deyo and Elixhauser comorbidity indexes. METHODS We derived the cardiac-specific comorbidity index from consecutive patients who were admitted to hospital at a tertiary-care cardiology hospital in Quebec. We used logistic regression analysis and incorporated age, sex and 22 clinically relevant comorbidities to build the index. We compared the cardiac-specific comorbidity index with refitted Charlson–Deyo and Elixhauser comorbidity indexes using the C-statistic and net reclassification improvement to predict in-hospital death, and the Akaike information criterion to predict length of stay. We validated our findings externally in an independent cohort obtained from a provincial registry of coronary disease in Alberta. RESULTS The novel cardiac-specific comorbidity index outperformed the refitted generic Charlson–Deyo and Elixhauser comorbidity indexes for predicting in-hospital mortality in the derivation population ( n = 10 137): C-statistic 0.95 (95% confidence interval CI 0.94–0.9) v. 0.81 (95% CI 0.77–0.84) and 0.86 (95% CI 0.82–0.89), respectively. In the validation population ( n = 17 877), the cardiac-specific comorbidity index was similarly better: C-statistic 0.92 (95% CI 0.89–0.94) v. 0.76 (95% CI 0.71–0.81) and 0.82 (95% CI 0.78–0.86), respectively, and also numerically outperformed the Charlson–Deyo and Elixhauser comorbidity indexes for predicting 1-year mortality (C-statistic 0.78 95% CI 0.76–0.80 v. 0.75 95% CI 0.73–0.77 and 0.77 95% CI 0.75–0.79, respectively). Similarly, the cardiac-specific comorbidity index showed better fit for the prediction of length of stay. The net reclassification improvement using the cardiac-specific comorbidity index for the prediction of death was 0.290 compared with the Charlson–Deyo comorbidity index and 0.192 compared with the Elixhauser comorbidity index. INTERPRETATION The cardiac-specific comorbidity index predicted in-hospital and 1-year death and length of stay in cardiovascular populations better than existing generic models. This novel index may be useful for research of cardiology outcomes performed with large administrative databases.
Abstract
We conducted a genome-wide association study of time to remission of COVID-19 symptoms in 1723 outpatients with at least one risk factor for disease severity from the COLCORONA clinical ...trial. We found a significant association at 5p13.3 (rs1173773;
P
= 4.94 × 10
–8
) near the natriuretic peptide receptor 3 gene (
NPR3
). By day 15 of the study, 44%, 54% and 59% of participants with 0, 1, or 2 copies of the effect allele respectively, had symptom remission. In 851 participants not treated with colchicine (placebo), there was a significant association at 9q33.1 (rs62575331;
P
= 2.95 × 10
–8
) in interaction with colchicine (
P
= 1.19 × 10
–5
) without impact on risk of hospitalisations, highlighting a possibly shared mechanistic pathway. By day 15 of the study, 46%, 62% and 64% of those with 0, 1, or 2 copies of the effect allele respectively, had symptom remission. The findings need to be replicated and could contribute to the biological understanding of COVID-19 symptom remission.
Abstract Background Worsening renal function during hospitalization for an acute coronary syndrome is strongly predictive of in-hospital and long-term outcome. However, the role of post-discharge ...worsening renal function has never been investigated in this setting. Methods We considered the placebo cohort of the AleCardio trial comparing aleglitazar with standard medical therapy among patients with type 2 diabetes mellitus and a recent acute coronary syndrome. Patients who had died or had been admitted to hospital for heart failure before the 6-month follow-up, as well as patients without complete renal function data, were excluded, leaving 2776 patients for the analysis. Worsening renal function was defined as a >20% reduction in estimated glomerular filtration rate from discharge to 6 months, or progression to macroalbuminuria. The Cox regression analysis was used to determine the prognostic impact of 6-month renal deterioration on the composite of all-cause death and hospitalization for heart failure. Results Worsening renal function occurred in 204 patients (7.34%). At a median follow-up of 2 years the estimated rates of death and hospitalization for heart failure per 100 person-years were 3.45 (95% confidence interval CI, 2.46-6.36) for those with worsening renal function, versus 1.43 (95% CI, 1.14-1.79) for patients with stable renal function. At the adjusted analysis worsening renal function was associated with the composite endpoint (hazard ratio 2.65; 95% CI, 1.57-4.49; P <.001). Conclusions Post-discharge worsening renal function is not infrequent among patients with type 2 diabetes and acute coronary syndromes with normal or mildly depressed renal function, and is a strong predictor of adverse cardiovascular events.
Objective To assess if right ventricular (RV) dysfunction is associated with increased mortality after cardiac surgery. Design Post-hoc analysis of a single-center double-blind randomized controlled ...trial. Setting University hospital. Participants A total of 120 patients undergoing simple or complex valvular surgery. Interventions Patients were randomized to receive intravenous amiodarone or placebo intraoperatively. As secondary analysis, patients were divided into those requiring or not requiring postoperative inotropic agents. Measurements and Main Results After cardiopulmonary bypass (CPB), there were significant increases in heart rate, cardiac index, systolic and mean arterial pressures, central venous pressure and pulmonary capillary wedge pressure with reduction in systemic vascular resistance (p<0.05). Right ventricular end-systolic area became larger in those without inotropes and tricuspid annular plane systolic excursion was reduced in all patients; mitral annular systolic velocities were higher in patients receiving inotropes. Both right- and left-sided Doppler signals were altered significantly after CPB, which may be attributed to increased filling pressure. Inotropic agents were required in 56 patients after CPB (47%). The use of inotropic agents was associated with increased left and right atrial velocities (p<0.05). There were no differences in postoperative complications between groups; however, the number of deaths at 6 years was increased in patients who received inotropes after CPB (p = 0.0247). Conclusions The increases in right-sided dimensions after CPB are associated with reduction in RV function and increased biventricular filling pressure, suggesting worsening biventricular function and interventricular dependence. Inotropic medications were associated with unaltered RV dimensions and increased biatrial activity.
Abstract Background Significant paravalvular leak (PVL) after prosthetic replacement can result in hemolysis and/or congestive heart failure (CHF). Percutaneous PVL reduction (PPVR) represents an ...alternative to repeat surgery for a selected population. The purpose of this study was to assess the procedural and long-term clinical efficacy of percutaneous PPVR and its effect on survival free of rehospitalization for CHF, surgical reintervention, and death. Methods We analyzed a cohort of 56 consecutive patients who underwent 61 PPVRs in our institution between June 2001 and December 2010. Procedural success was defined as a reduction in regurgitation severity free from procedural complications. Patients were followed-up for vital status, clinical events, and symptoms. Results Patients were aged 65 ± 11 years, with an average logistic EuroSCORE of 19 ± 14%. Indications for PPVR included CHF (61%), hemolysis (9%), or both (30%), caused by mitral (n = 44) or aortic (n = 12) PVL. Procedural success was achieved in 75% of cases. Three major complications, including 2 deaths, occurred during the initial 30-day follow-up in the 42 patients who were treated with a device. After adjusting for the logistic EuroSCORE, prosthesis type (mitral vs aortic), and time interval since the last valve surgery, a successful PPVR was associated with a better survival free of rehospitalisation for CHF, need for surgical reintervention, and death compared with patients with a failed PPVR. (hazard ratio = 0.34; 95% confidence interval, 0.17-0.71). Conclusions PPVR is associated with a reasonable rate of procedural success and favourable cardiovascular outcomes, and represents an appropriate option when technically possible.
In patients with anterior ST-elevation myocardial infarction (STEMI) and new-onset antero-apical wall motion abnormalities (WMAs), whether the rate of prophylaxis against left ventricular thrombus ...and outcomes differ between men and women is unknown.
A multicentre retrospective cohort study of patients with STEMI and new-onset antero-apical WMAs treated with primary percutaneous coronary intervention was conducted. Patients with an established indication of oral anticoagulation (OAC) were excluded. The rates of triple therapy (double antiplatelet therapy + OAC) at discharge were compared for women vs men. The rates of net adverse clinical events, a composite of mortality, myocardial infarction, stroke or transient ischemic attack, systemic thromboembolism or Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding at 6 months were compared across sex using a multivariate logistic regression model.
A total of 1664 patients were included in the primary analysis, of whom 402 (24.2%) were women and 1262 (75.8%) were men. A total of 138 women (34.3%) and 489 men (38.7%) received a triple therapy prescription at discharge (P = 0.11). At 6 months, 33 women (8.2%) and 96 men (7.6%) experienced a net adverse clinical event (adjusted odds ratio 0.82; 95% confidence interval 0.49-1.37). No difference occurred in the risk of bleeding events and ischemic events between men and women, when these were analyzed separately.
The rates of OAC prescription for left ventricular thrombus prophylaxis and clinical outcomes at 6 months were similar in women and men following anterior STEMI with new-onset antero-apical WMAs.
On ignore si le taux de prophylaxie contre le thrombus ventriculaire gauche et les résultats thérapeutiques diffèrent entre les hommes et les femmes qui ont subi un infarctus du myocarde avec élévation du segment ST (STEMI) antérieur et ont des anomalies du mouvement pariétal (AMP) antéroapical d’apparition récente.
Nous avons mené une étude de cohorte rétrospective multicentrique auprès de patients qui ont subi un STEMI et ont des AMP d’apparition récente traitées par une intervention coronarienne percutanée primaire. Nous avons exclu les patients chez lesquels il existait une indication établie à l’anticoagulation orale (ACO). Nous avons comparé les taux de trithérapie (bithérapie antiplaquettaire + ACO) à la sortie de l’hôpital entre les femmes et les hommes. Nous avons comparé les taux d’événements indésirables cliniques nets, le critère composite de mortalité, d’infarctus du myocarde, d’accident vasculaire cérébral ou d’accident ischémique transitoire, la thromboembolie systémique ou l’hémorragie de type 3 ou 5 selon le Bleeding Academic Research Consortium (BARC) après 6 mois entre les sexes au moyen du modèle de régression logistique multivariée.
Au sein des 1 664 patients de l’analyse principale, 402 (24,2 %) étaient des femmes et 1262 (75,8 %) étaient des hommes. Un total de 138 femmes (34,3 %) et de 489 hommes (38,7 %) ont reçu une ordonnance de trithérapie à la sortie de l’hôpital (P = 0,11). Après 6 mois, 33 femmes (8,2 %) et 96 hommes (7,6 %) ont subi un événement indésirable net (rapport de cotes ajusté 0,82 ; intervalle de confiance à 95 % 0,49-1,37). Aucune différence n’a été notée dans le risque d’événements hémorragiques et d’événements ischémiques entre les hommes et les femmes lorsque ces événements étaient analysés séparément.
Les taux d’ordonnances d’ACO en prophylaxie du thrombus ventriculaire gauche et les résultats cliniques après 6 mois étaient similaires entre les femmes et les hommes à la suite du STEMI antérieur et des AMP antéroapicale d’apparition récente.
Abstract Background High-intensity interval exercise (HIIE) is gaining in popularity in fitness centres, even among coronary heart disease (CHD) patients. However, whether HIIE can have deleterious ...acute effects on the vasculature in CHD has not been studied. We hypothesized that when compared with moderate-intensity continuous exercise (MICE), a single bout of HIIE could lead to vascular damage and increasing numbers of circulating endothelial and platelet microparticles (EMPs, PMPs) in stable, physically fit CHD patients. Methods Nineteen male CHD patients (aged 62 ± 11 years) underwent, in random order, a single session of HIIE corresponding to 15-second intervals at 100% of peak power output and 15-second passive recovery intervals, and an isocaloric MICE session. EMPs (CD31+ and/or CD62E+ and CD42b− ); PMPs (CD42b+ ); nitrates and nitrites; prostacycline; and troponin T, cardiac form (cTnT), were measured 10 minutes before exercise and 20 minutes, 24 hours, and 72 hours after both exercise sessions. Results EMPs, PMPs, nitrates and nitrites, prostacycline, and cTnT remained unchanged after both HIIE and MICE exercise sessions. Initial EMP concentration correlated inversely with EMP concentration 20 minutes post exercise, irrespective of exercise modality ( r = 0.78, P < 0.0001). Conclusions A single HIIE session with very short exercise and passive recovery periods appears safe and does not induce changes to markers of endothelial function. Future studies are required to determine the safety of a long-term HIIE training program.
In the Digitalis Investigation Group trial, digoxin-associated decrease in the combined end point of heart failure (HF) hospitalization or HF mortality was significant in systolic but not in ...diastolic HF. To assess whether this apparent disparity could be explained by differences in baseline characteristics and sample size, we used propensity score matching to assemble a cohort of 916 pairs of patients with systolic and diastolic HF who were balanced in all measured baseline covariates. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) of the effect of digoxin on outcomes separately in systolic and diastolic HF, at 2 years (protocol prespecified), and at the end of 3.2 years of median follow-up. HF hospitalization or HF mortality occurred in 28% and 32% of patients with systolic HF (HR digoxin vs placebo 0.85, 95% CI 0.67 to 1.08, p = 0.188) and 20% and 25% in those with diastolic HF (HR 0.79, 95% CI 0.60 to 1.03, p = 0.085) receiving digoxin and placebo, respectively. At 2 years, HRs for this combined end point were similar for systolic HF (0.72, 95% CI 0.55 to 0.95, p = 0.022) and diastolic HF (0.69, 95% CI 0.50 to 0.95, p = 0.025). Digoxin also decreased 2-year HF hospitalization in systolic HF (HR 0.73, 95% CI 0.54 to 0.97, p = 0.033) and diastolic HF (HR 0.64, 95% CI 0.45 to 0.90, p = 0.010). In conclusion, as in patients with systolic HF, digoxin was equally effective in those with diastolic HF, who constitute half of all patients with HF, yet have few evidence-based therapeutic options.
Abstract Background We evaluated pulmonary production of osteopontin (OPN) in left ventricular systolic dysfunction (LVSD) and after cardiopulmonary bypass surgery (CPB). OPN is a phosphoglycoprotein ...involved in inflammation and remodeling. In subjects with LVSD, plasma OPN correlates with prognosis but its origin is unknown. We hypothesized that the lungs produce OPN and that this could be affected by LVSD and CPB. Methods and Results Subjects with (n = 57; left ventricular ejection fraction LVEF 32 ± 8%) and without (n = 63; LVEF 59 ± 7%) LVSD were studied during CPB. Arterial and venous OPN plasma levels were determined. Arterial and venous OPN levels were higher in LVSD ( P = .0290). For both groups, levels dropped 1 hour after surgery and nearly doubled 24 hours after ( P < .0001 vs basal). Notably, there was a significant positive arteriovenous gradient with arterial levels higher than venous levels. Arteriovenous differences were statistically significant at baseline ( P = .0120) and 1 hour ( P < .0001) but not at 24 hours ( P = .0649). Arterial levels in heart failure correlated inversely with renal function ( P = .016) and positively with mean pulmonary pressure ( P = .028), heart rate ( P = .036), and C-reactive protein ( P = .047). Conclusions There is production of circulating OPN by the lungs, unaffected by LVSD or CPB. This likely represents an overflow from local lung production and does not contribute to increased levels in LVSD or after CPB.
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