La congestion veineuse comme déterminant des interactions cardio-rénales et cardio-intestinales en insuffisance cardiaque aiguë

Les interactions entre coeur défaillant et organes périphériques sont centrales pour la compréhension de la variabilité de la présentation clinique, de la progression et du pronostic du syndrome insuffisance cardiaque. La congestion veineuse est considérée comme un des éléments les plus importants qui sous-tendent les interactions cardio-rénales et cardio-intestinales, faisant du retour à l’euvolémie un objectif majeur de la prise en charge du patient décompensé. De fait, la caractérisation non invasive du statut volémique permettrait d’optimiser la prise en charge en facilitant l’adaptation du traitement déplétif au cas par cas. L’objectif de ce travail est d’explorer l’effet délétère de la congestion veineuse chez le patient insuffisant cardiaque, en particulier en termes de dysfonction des organes cibles, et de répertorier l’intérêt de l’échographie multi-site pour la caractérisation du statut volémique dans cette population.Venous congestion has been shown to play a major role in worsening renal function in acute decompensated heart failure, and recent data have challenged the assumption that end-organ dysfunction was driven by other hemodynamic alterations in patients with heart failure. Decongestion is thus considered as a major therapeutic goal in the management of patients with acute heart failure. As such, real-time assessment of patient’s fluid status may allow for a better management of patients with heart failure, enabling for a personalized management. The aim of this work is to explore the deleterious effect of venous congestion in patient with heart failure, particularly in terms of end-organ dysfunction. We also aimed to characterize the role of extra cardiac ultrasound for the assessment of the volume status in patients with heart failure

Beneficial effects of ivabradine in patients with heart failure, low ejection fraction, and heart rate above 77 b.p.m.

Aims: Ivabradine has been approved in heart failure with reduced ejection fraction (HFrEF) and elevated heart rate despite guideline‐directed medical therapy (GDMT) to reduce cardiovascular (CV) death and hospitalization for worsening HF. The median value of 77 b.p.m. is the lower bound selected for the regulatory approval in Canada, South Africa, and Australia. Patient‐reported outcomes (PROs) including symptoms, quality of life, and global assessment are considered of major interest in the global plan of care of patients with HF. However, the specific impact of GDMT, and specifically ivabradine, on PRO remains poorly studied. In the subgroup of patients from the Systolic Heart failure treatment with the If inhibitor ivabradine Trial (SHIFT) who had heart rate above the median of 77 b.p.m. (pre‐specified analysis) and for whom the potential for improvement was expected to be larger, we aimed (i) to evaluate the effects of ivabradine on PRO (symptoms, quality of life, and global assessment); (ii) to consolidate the effects of ivabradine on the primary composite endpoint of CV death and hospitalization for HF; and (iii) to reassess the effects of ivabradine on left ventricular (LV) remodelling. Methods and results: Comparisons were made according to therapy, and proportional hazards models (adjusted for baseline beta‐blocker therapy) were used to estimate the association between ivabradine and various outcomes. In SHIFT, n = 3357 (51.6%) patients had a baseline heart rate > 77 b.p.m. After a median follow‐up of 22.9 months (inter‐quartile range 18–28 months), ivabradine on top of GDMT improved symptoms (28% vs. 23% improvement in New York Heart Association functional class, P = 0.0003), quality of life (5.3 vs. 2.2 improvement in Kansas City Cardiomyopathy Questionnaire overall summary score, P = 0.005), and global assessment [from both patient (improved in 72.3%) and physician (improved in 61.0%) perspectives] significantly more than did placebo (both P < 0.0001). Ivabradine induced a 25% reduction in the combined endpoint of CV death and hospitalization for HF (hazard ratio 0.75; P < 0.0001), which translates into a number of patients needed to be treated for 1 year of 17. Patients under ivabradine treatment demonstrated a significant reduction in LV dimensions when reassessed at 8 months (P < 0.05). Conclusions: In patients with chronic HFrEF, sinus rhythm, and a heart rate > 77 b.p.m. while on GDMT, the present analysis brings novel insights into the role of ivabradine in improving the management of HFrEF, particularly with regard to PRO (ISRCTN70429960)

Impact of smoking on cardiovascular outcomes in patients with stable coronary artery disease

Aims: Smoking is a major preventable risk factor for cardiovascular disease and mortality. However, the ‘smoker’s paradox’ suggests that it is associated with better survival after acute myocardial infarction. We aimed to investigate the impact of smoking on mortality and cardiovascular outcomes in patients with stable coronary artery disease. Methods: The international CLARIFY registry included 32,703 patients with stable coronary artery disease between 2009 and 2010. Among the 32,378 patients included in the present analysis, Cox proportional hazards models (adjusted for age, sex, geographic region, prior myocardial infarction, and revascularization status) were used to estimate associations between smoking status and outcomes. Patients were stratified as follows: 41.3% of patients never smoked, 12.5% were current smokers and 46.2% were former smokers. Results: Current smokers were younger than never-smokers and former smokers (59 vs. 66 and 64 years old, respectively, p < 0.0001). There were more men among current or former smokers compared with never-smokers. Compared with never-smokers, both current and former smokers were at higher risk of all-cause death (hazard ratio = 1.96 and 1.37) and cardiovascular death (hazard ratio = 1.92 and 1.38) within five years (all p < 0.05). Similarly graded and increased risks were present for myocardial infarction and the composite of cardiovascular death, myocardial infarction and stroke (all p < 0.05). Conclusion: In contrast to the ‘smoker’s paradox’, current smokers with stable coronary artery disease have a greatly increased risk of future cardiovascular events, including mortality, compared with never-smokers. In former smokers, cardiovascular risk remains elevated albeit at an intermediate level between that of current and never-smokers, reinforcing the importance of smoking cessation. (ISRCTN43070564)

Potassium reduction with sodium zirconium cyclosilicate in patients with heart failure

Aims: Several patients with heart failure and reduced ejection fraction (HFrEF) do not receive renin–angiotensin–aldosterone system (RAAS) inhibitors at the recommended dose or at all, frequently due to actual or feared hyperkalaemia. Sodium zirconium cyclosilicate (SZC) is an orally administered non-absorbed intestinal potassium binder proven to lower serum potassium concentrations. Methods and results: PRIORITIZE-HF was an international, multicentre, parallel-group, randomized, double-blind, placebo-controlled study to evaluate the benefits and risks of using SZC to intensify RAAS inhibitor therapy. Patients with symptomatic HFrEF were eligible and randomly assigned to receive SZC 5 g or placebo once daily for 12 weeks. Doses of study medication and RAAS inhibitors were titrated during the treatment period. The primary endpoint was the proportion of patients at 12 weeks in the following categories: (i) any RAAS inhibitor at less than target dose, and no MRA; (ii) any RAAS inhibitor at target dose and no MRA; (ii) MRA at less than target dose; and (iv) MRA at target dose. Due to challenges in participant management related to the COVID-19 pandemic, the study was prematurely terminated with 182 randomized patients. There was no statistically significant difference in the distribution of patients by RAAS inhibitor treatment categories at 3 months (P = 0.43). The proportion of patients at target MRA dose was numerically higher in the SZC group (56.4%) compared with the placebo group (47.0%). Overall, SZC was well tolerated. Conclusions: PRIORITIZE-HF was terminated prematurely due to COVID-19 and did not demonstrate a statistically significant increase in the intensity of RAAS inhibitor therapies with the potassium-reducing agent SZC compared with placebo

Pharmacogenomics of the efficacy and safety of Colchicine in COLCOT

© 2021 The Authors. Circulation: Genomic and Precision Medicine is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited and is not used for commercial purposes.Background: The randomized, placebo-controlled COLCOT (Colchicine Cardiovascular Outcomes Trial) has shown the benefits of colchicine 0.5 mg daily to lower the rate of ischemic cardiovascular events in patients with a recent myocardial infarction. Here, we conducted a post hoc pharmacogenomic study of COLCOT with the aim to identify genetic predictors of the efficacy and safety of treatment with colchicine. Methods: There were 1522 participants of European ancestry from the COLCOT trial available for the pharmacogenomic study of COLCOT trial. The pharmacogenomic study's primary cardiovascular end point was defined as for the main trial, as time to first occurrence of cardiovascular death, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina requiring coronary revascularization. The safety end point was time to the first report of gastrointestinal events. Patients' DNA was genotyped using the Illumina Global Screening array followed by imputation. We performed a genome-wide association study in colchicine-treated patients. Results: None of the genetic variants passed the genome-wide association study significance threshold for the primary cardiovascular end point conducted in 702 patients in the colchicine arm who were compliant to medication. The genome-wide association study for gastrointestinal events was conducted in all 767 patients in the colchicine arm and found 2 significant association signals, one with lead variant rs6916345 (hazard ratio, 1.89 [95% CI, 1.52-2.35], P=7.41×10-9) in a locus which colocalizes with Crohn disease, and one with lead variant rs74795203 (hazard ratio, 2.51 [95% CI, 1.82-3.47]; P=2.70×10-8), an intronic variant in gene SEPHS1. The interaction terms between the genetic variants and treatment with colchicine versus placebo were significant. Conclusions: We found 2 genomic regions associated with gastrointestinal events in patients treated with colchicine. Those findings will benefit from replication to confirm that some patients may have genetic predispositions to lower tolerability of treatment with colchicine.info:eu-repo/semantics/publishedVersio

Surgical Management of Undiagnosed Laceration of Superior Vena Cava Caused by Blunt Trauma

International audienceIntrapericardial rupture of the superior vena cava resulting from blunt thoracic trauma is a rare and life-threatening condition that has to be ruled out in the presence of signs of cardiac tamponade and a history of blunt thoracic trauma. We report the case of undiagnosed superior vena cava laceration caused by a high-speed road traffic accident in a 25 year-old patient revealed by cardiac tamponade. We highlight the need of urgent surgical exploration in all patients whose condition is unstable in the setting of blunt thoracic trauma regardless of imaging conclusions

Colchicine for community-treated patients with COVID-19 (COLCORONA): a phase 3, randomised, double-blinded, adaptive, placebo-controlled, multicentre trial

Background Evidence suggests a role for excessive inflammation in COVID-19 complications. Colchicine is an oral anti-inflammatory medication beneficial in gout, pericarditis, and coronary disease. We aimed to investigate the effect of colchicine on the composite of COVID-19-related death or hospital admission. Methods The present study is a phase 3, randomised, double-blind, adaptive, placebo-controlled, multicentre trial. The study was done in Brazil, Canada, Greece, South Africa, Spain, and the USA, and was led by the Montreal Heart Institute. Patients with COVID-19 diagnosed by PCR testing or clinical criteria who were not being treated in hospital were eligible if they were at least 40 years old and had at least one high-risk characteristic. The randomisation list was computer-generated by an unmasked biostatistician, and masked randomisation was centralised and done electronically through an automated interactive web-response system. The allocation sequence was unstratified and used a 1:1 ratio with a blocking schema and block sizes of six. Patients were randomly assigned to receive orally administered colchicine (0middot5 mg twice per day for 3 days and then once per day for 27 days thereafter) or matching placebo. The primary efficacy endpoint was the composite of death or hospital admission for COVID-19. Vital status at the end of the study was available for 97middot9% of patients. The analyses were done according to the intention-to-treat principle. The COLCORONA trial is registered with ClinicalTrials.gov (NCT04322682) and is now closed to new participants. Findings Trial enrolment began in March 23, 2020, and was completed in Dec 22, 2020. A total of 4488 patients (53middot9% women; median age 54middot0 years, IQR 47middot0-61middot0) were enrolled and 2235 patients were randomly assigned to colchicine and 2253 to placebo. The primary endpoint occurred in 104 (4middot7%) of 2235 patients in the colchicine group and 131 (5middot8%) of 2253 patients in the placebo group (odds ratio [OR] 0middot79, 95middot1% CI 0middot61-1middot03; p=0middot081). Among the 4159 patients with PCR-confirmed COVID-19, the primary endpoint occurred in 96 (4middot6%) of 2075 patients in the colchicine group and 126 (6middot0%) of 2084 patients in the placebo group (OR 0middot75, 0middot57-0middot99; p=0middot042). Serious adverse events were reported in 108 (4middot9%) of 2195 patients in the colchicine group and 139 (6middot3%) of 2217 patients in the placebo group (p=0middot051); pneumonia occurred in 63 (2middot9%) of 2195 patients in the colchicine group and 92 (4middot1%) of 2217 patients in the placebo group (p=0middot021). Diarrhoea was reported in 300 (13middot7%) of 2195 patients in the colchicine group and 161 (7middot3%) of 2217 patients in the placebo group (p<0middot0001). Interpretation In community-treated patients including those without a mandatory diagnostic test, the effect of colchicine on COVID-19-related clinical events was not statistically significant. Among patients with PCR-confirmed COVID-19, colchicine led to a lower rate of the composite of death or hospital admission than placebo. Given the absence of orally administered therapies to prevent COVID-19 complications in community-treated patients and the benefit of colchicine in patients with PCR-proven COVID-19, this safe and inexpensive anti-inflammatory agent could be considered for use in those at risk of complications. Notwithstanding these considerations, replication in other studies of PCR-positive community-treated patients is recommended. Funding The Government of Quebec, the Bill & Melinda Gates Foundation, the National Heart, Lung, and Blood Institute of the US National Institutes of Health, the Montreal Heart Institute Foundation, the NYU Grossman School of Medicine, the Rudin Family Foundation, and philanthropist Sophie Desmarais. Copyright (c) 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

Heart Transplantation for Peripartum Cardiomyopathy: A Single-Center Experience

Abstract Background: Peripartum cardiomyopathy is an idiopathic disorder defined by the occurrence of acute heart failure during late pregnancy or post-partum period in the absence of any other definable cause. Its clinical course is variable and severe cases might require heart transplantation. Objective: To investigate long-term outcomes after heart transplantation (HT) for peripartum cardiomyopathy (PPCM). Methods: Out of a single-center series of 1938 HT, 14 HT were performed for PPCM. We evaluated clinical characteristics, transplant-related complications, and long-term outcomes, in comparison with 28 sex-matched controls. Primary endpoint was death from any cause; secondary endpoints were transplant-related complications (rejection, infection, cardiac allograft vasculopathy). A value of p 0.05), except for a higher use of inotropes at the time of HT in PPCM group (p = 0.03). During a median follow-up of 7.7 years, 16 patients died, 3 (21.5%) in PPCM group and 13 (46.5%) in control group. Mortality was significantly lower in PPCM group (p = 0.03). No significant difference was found in terms of transplant-related complications (p > 0.05). Conclusions: Long-term outcomes following HT for PPCM are favorable. Heart transplantation is a valuable option for PPCM patients who did not recover significantly under medical treatment