Beta Blockers Improve Prognosis When Used Early in Patients with Cardiogenic Shock: An Analysis of the FRENSHOCK Multicenter Prospective Registry.

BACKGROUND: Beta blockers (BBs) are a cornerstone for patients with heart failure (HF) and ventricular dysfunction. However, their use in patients recovering from a cardiogenic shock (CS) remains a bone of contention, especially regarding whether and when to reintroduce this class of drugs. METHODS: FRENSHOCK is a prospective multicenter registry including 772 CS patients from 49 centers. Our aim was to compare outcomes (1-month and 1-year all-cause mortality) between CS patients taking and those not taking BBs in three scenarios: (1) at 24 h after CS; (2) patients who did or did not discontinue BBs within 24 h; and (3) patients who did or did not undergo the early introduction of BBs. RESULTS: Among the 693 CS included, at 24 h after the CS event, 95 patients (13.7%) were taking BB, while 598 (86.3%) were not. Between the groups, there were no differences in terms of major comorbidities or initial CS triggers. Patients receiving BBs at 24 h presented a trend toward reduced all-cause mortality both at 1 month (aHR = 0.61, 95% CI 0.34 to 1.1, p = 0.10) and 1 year, which was, in both cases, not significant. Compared with patients who discontinued BBs at 24 h, patients who did not discontinue BBs showed lower 1-month mortality (aHR = 0.43, 95% CI 0.2 to 0.92, p = 0.03) and a trend to lower 1-year mortality. No reduction in outcomes was observed in patients who underwent an early introduction of BB therapy. CONCLUSIONS: BBs are drugs of first choice in patients with HF and should also be considered early in patients with CS. In contrast, the discontinuation of BB therapy resulted in increased 1-month all-cause mortality and a trend toward increased 1-year all-cause mortality.

Anti-Inflammatory Drug Candidates for Prevention and Treatment of Cardiovascular Diseases.

Incidence and mortality rates for cardiovascular disease are declining, but it still remains a major cause of morbidity and mortality. Drug treatments to slow the progression of atherosclerosis focus on reducing cholesterol levels. The paradigm shift to consider atherosclerosis an inflammatory disease by itself has led to the development of new treatments. In this article, we discuss the pathophysiology of inflammation and focus attention on therapeutics targeting different inflammatory pathways of atherosclerosis and myocardial infarction. In atherosclerosis, colchicine is included in new recommendations, and eight randomized clinical trials are testing new drugs in different inflammatory pathways. After a myocardial infarction, no drug has shown a significant benefit, but we present four randomized clinical trials with new treatments targeting inflammation.

Acute Myocarditis Induced by Hepatitis E: An Uncommon Association.

Acute myocarditis is often caused by viral infections. Hepatitis E infection inflicts over 20 million people worldwide each year. Common extra-hepatic manifestations of hepatitis E infection include neurologic, hematologic, and renal sequelae.1 Acute myocarditis, defined by the presence of myocardial inflammatory infiltrates associated with nonischemic myocytic necrosis, is uncommon. Published reports of such cases are limited, and here we present the case of a 45-year-old man with acute myocarditis from hepatitis E infection. This case is the first described in Europe of acute myocarditis associated with hepatitis E infection.

La myocardite aiguë est souvent d'origine virale. Chaque année, plus de 20 millions de personnes dans le monde contractent l'hépatite E. Les manifestations extrahépatiques courantes de l'hépatite E comprennent des atteintes neurologiques, hématologiques et rénales. La myocardite aiguë, définie par la présence d'infiltrats inflammatoires myocardiques associés à une nécrose myocytaire non ischémique, est rare. Peu de cas ont été rapportés dans la littérature médicale. Nous abordons ici le cas d'un homme de 45 ans présentant une myocardite aiguë liée à une infection par le virus de l'hépatite E. Il s'agit du premier cas de ce genre décrit en Europe.

Impact of Daily Bedside Echocardiographic Assessment on Readmissions in Acute Heart Failure: A Randomized Clinical Trial.

Acute heart failure (AHF) management is challenging, with high morbidity and readmission rates. There is little evidence of the benefit of HF monitoring during hospitalization. The aim of the study was to assess whether daily bedside echocardiographic monitoring (JetEcho) improved outcomes in AHF. In this prospective, open, two parallel-arm study (clinicaltrials.gov: NCT02892227), participants from two university hospitals were randomized to either standard of care (SC) or daily treatment adjustment including diuretics guided by JetEcho evaluating left ventricular filling pressure and volemia. The primary outcome was 30-day readmission rate. Key secondary outcomes were six-month cumulative incidence death, worsening HF during hospitalization and increasing of myocardial and renal biomarkers. From 250 included patients, 115 were finally analyzed in JetEcho group and 112 in SC group. Twenty-two (19%) patients were readmitted within 30 days in JetEcho group and 17 (15%) in SC group (relative risk [RR] 1.26; 95% confidence interval [CI], 0.70−2.24; p = 0.4). Worsening HF occurred in 17 (14%) patients in the JetEcho group and 24 (20%) in the SC group (RR 0.7; 95% [CI] 0.39 to 1.2; p = 0.2). No significant difference was found between the two groups concerning natriuretic peptides and renal function (p > 0.05 for all). The cumulative incidence rate of death from any cause at six months from discharge was 8.7% in the JetEcho group and 11.6% in the SC group (HR 0.63, 95% [CI] 0.3−1.4, p = 0.3). In AHF patients, a systematic daily bedside echocardiographic monitoring did not reduce 30-day readmission rate for HF and short-term clinical outcomes.

Could a Multi-Marker and Machine Learning Approach Help Stratify Patients with Heart Failure?

Half of the patients with heart failure (HF) have preserved ejection fraction (HFpEF). To date, there are no specific markers to distinguish this subgroup. The main objective of this work was to stratify HF patients using current biochemical markers coupled with clinical data. The cohort study included HFpEF (n = 24) and heart failure with reduced ejection fraction (HFrEF) (n = 34) patients as usually considered in clinical practice based on cardiac imaging (EF ≥ 50% for HFpEF; EF < 50% for HFrEF). Routine blood tests consisted of measuring biomarkers of renal and heart functions, inflammation, and iron metabolism. A multi-test approach and analysis of peripheral blood samples aimed to establish a computerized Machine Learning strategy to provide a blood signature to distinguish HFpEF and HFrEF. Based on logistic regression, demographic characteristics and clinical biomarkers showed no statistical significance to differentiate the HFpEF and HFrEF patient subgroups. Hence a multivariate factorial discriminant analysis, performed blindly using the data set, allowed us to stratify the two HF groups. Consequently, a Machine Learning (ML) strategy was developed using the same variables in a genetic algorithm approach. ML provided very encouraging explorative results when considering the small size of the samples applied. The accuracy and the sensitivity were high for both validation and test groups (69% and 100%, 64% and 75%, respectively). Sensitivity was 100% for the validation and 75% for the test group, whereas specificity was 44% and 55% for the validation and test groups because of the small number of samples. Lastly, the precision was acceptable, with 58% in the validation and 60% in the test group. Combining biochemical and clinical markers is an excellent entry to develop a computer classification tool to diagnose HFpEF. This translational approach is a springboard for improving new personalized treatment methods and identifying "high-yield" populations for clinical trials.

Colchicine to Prevent Sympathetic Denervation after an Acute Myocardial Infarction: The COLD-MI Trial Protocol.

Inflammatory processes are deeply involved in ischemia-reperfusion injuries (IRI) and ventricular remodelling (VR) after a ST-segment elevation myocardial infarction (STEMI). They are associated with clinical adverse events (heart failure and cardiovascular death) adding damage to the myocardium after reperfusion. Moreover, acute myocardial infarction (AMI) induces a local sympathetic denervation leading to electrical instability and arrythmia. Colchicine, a well-known alkaloid with direct anti-inflammatory effects, was shown to reduce the myocardial necrosis size and limit the VR. In a recent proof of concept study, colchicine appears to prevent sympathetic denervation in a mice model of ischemia/reperfusion, but not in the necrosis or in the border zone areas. The Colchicine to Prevent Sympathetic Denervation after an AMI study (COLD-MI) is an ongoing, confirmative, prospective, monocentre, randomized, open-label trial. The COLD-MI trial aims to evaluate the intensity of sympathetic denervation after AMI and its potential modulation due to low dose colchicine. Sympathetic denervation will be noninvasively evaluated using single-photon emission computed tomography (SPECT). After a first episode of STEMI (Initial TIMI flow ≤ 1) and primary percutaneous coronary intervention (PPCI), patients will be randomized (n = 56) in a 1:1 ratio to either receive colchicine or not for 30 days. The primary end point will be the percentage of myocardial denervation measured by 123I-metaiodobenzylguanidine (123I-MIBG) SPECT at a 6-month follow-up. The main secondary end points will be basic ECG parameters (QRS duration, corrected QT) and HRV parameters from a 24 hour-recording Holter at 1- and 6-months follow-up. Results from this study will contribute to a better understanding of the cardioprotective effect of colchicine after AMI. The present study describes the rationale, design, and methods of the trial.

Soluble urokinase-type plasminogen activator receptor strongly predicts global mortality in acute heart failure patients: insight from the STADE-HF registry.

BACKGROUND: Whether soluble urokinase-type plasminogen activator receptor (suPAR) could be a valuable prognostic indicator remains uncertain. MATERIALS & METHODS: Patients from STADE-HF (Soluble Suppression of Tumorigenesis-2 as a Help for Management of Diagnosis, Evaluation and Management of Heart Failure) were included for analysis. RESULTS: 95 patients were included. The suPAR level of expression was significantly higher in the group of patients who died at one month (7.90 ± 4.35 ng/ml vs 11.94 ± 6.86 ng/ml; p < 0.05) or 1 year (7.28 ± 4.27 ng/ml vs 11.81 ± 4.88 ng/ml; p < 0.01), but there was no significant difference according to the readmission. CONCLUSION: High suPAR levels during hospitalization for acute heart failure were highly predictive for the risk of mortality, but not the risk of readmission.

Idarucizumab (Praxbind®) for dabigatran reversal in patients undergoing heart transplantation: a cohort of ten patients.

BACKGROUND: Novel oral anticoagulants are used in atrial fibrillation. Idarucizumab has been approved for reversal of dabigatran in situations of life-threatening hemorrhage or emergency surgery. OBJECTIVES: We report a single center experience of ten patients on dabigatran therapy who were given idarucizumab prior to heart transplantation. METHODS & RESULTS: The mean plasma concentration of dabigatran prior to reversal was 139 ± 89 ng/ml. Hemoglobin, hematocrit and platelet levels were decreased after surgery. Surgical procedures were successfully performed with no increased risk, especially regarding bleeding complications. All patients were alive after 90 days. CONCLUSION: Dabigatran reversal with idarucizumab in contexts of emergency surgery/urgent procedures is an attractive and safe option to be taken into consideration for patients with end stage heart disease awaiting transplantation and indication of anticoagulant therapy.

Conception and bicentric validation of the proSCANNED score, a simplified bedside prognostic score for Heart Failure patients.

A simple and accurate prognostic tool for Heart Failure (HF) patients is critical to improve follow-up. Different risk scores are accurate but with limited clinical applicability. The current study aims to derive and validate a simple predictive tool for HF prognosis. French outpatients with stable HF of two university hospitals were included in the derivation (N = 134) or in the validation (N = 274) sample and followed up for a median of 23 months. Potential predictors were variables with known association with mortality and easily available. The proSCANNED risk score was derived using a parametric survival model on complete case data; it includes 8 binary variables and its values are 0-8. In the validation sample, the ability of the score to discriminate the 1-year vital status was moderate (AUC = 0.71, IC95% = [0.64-0.71]). However, the stratification of the score in three groups showed a good calibration for patients in the low- and medium-risk risk group. The proSCANNED score is an easy-to-use tool in clinical practice with a good discrimination, stability, and calibration sufficient to improve the medical care of patients. Other follow up studies are necessary to assess score applicability in larger populations, and its impact.

Long term pronostic value of suPAR in chronic heart failure: reclassification of patients with low MAGGIC score.

OBJECTIVES: Inflammation is a hallmark of heart failure (HF) and among inflammatory biomarkers, the most studied remains the C-reactive protein (CRP). In recent years several biomarkers have emerged, such as sST2 and soluble urokinase-type plasminogen activator receptor (suPAR). This study set out to examine the relative importance of long-time prognostic strength of suPAR and the potential additive information on patient risk with chronic HF in comparison with pronostic value of CRP and sST2. METHODS: Demographics, clinical and biological variables were assessed in a total of 182 patients with chronic HF over median follow-up period of 80 months. Inflammatory biomarkers (i.e., CRP, sST2, and suPAR) were performed. RESULTS: In univariate Cox regression analysis age, NYHA class, MAGGIC score and the five biomarkers (N-terminal pro brain natriuretic peptide [NT-proBNP], high-sensitive cardiac troponin T [hs-cTnT], CRP, sST2, and suPAR) were associated with both all-cause and cardiovascular mortality. In the multivariate model, only NT-proBNP, suPAR, and MAGGIC score remained independent predictors of all-cause mortality as well as of cardiovascular mortality. Risk classification analysis was significantly improved with the addition of suPAR particularly for all-cause short- and long-term mortality. Using a classification tree approach, the same three variables could be considered as significant classifier variables to predict all-cause or cardiovascular mortality and an algorithm were reported. We demonstrated the favorable outcome associated with patients with a low MAGGIC score and a low suPAR level by comparison to patients with low MAGGIC score but high suPAR values. CONCLUSIONS: The main findings of our study are (1) that among the three inflammatory biomarkers, only suPAR levels were independently associated with 96-month mortality for patients with chronic HF and (2) that an algorithm based on clinical score, a cardiomyocyte stress biomarker and an inflammatory biomarker could help to a more reliable long term risk stratification in heart failure.

Acute Coronary Syndrome in the Era of SARS-CoV-2 Infection: A Registry of the French Group of Acute Cardiac Care.

BACKGROUND: In this study, we aimed to report clinical characteristics and outcomes of patients with and without SARS-CoV-2 infection who were referred for acute coronary syndrome (ACS) during the peak of the pandemic in France. METHODS: We included all consecutive patients referred for ST-elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) during the first 3 weeks of April 2020 in 5 university hospitals (Paris, south, and north of France), all performing primary percutaneous coronary intervention. RESULTS: The study included 237 patients (67 ± 14 years old; 69% male), 116 (49%) with STEMI and 121 (51%) with NSTEMI. The prevalence of SARS-CoV-2-associated ACS was 11% (n = 26) and 11 patients had severe hypoxemia on presentation (mechanical ventilation or nasal oxygen > 6 L/min). Patients were comparable regarding medical history and risk factors, except a higher prevalence of diabetes mellitus in SARS-CoV-2 patients (53.8% vs 25.6%; P = 0.003). In SARS-CoV-2 patients, cardiac arrest on admission was more frequent (26.9% vs 6.6%; P < 0.001). The presence of significant coronary artery disease and culprit artery occlusion in SARS-CoV-2 patients respectively, was 92% and 69.4% for those with STEMI, and 50% and 15.5% for those with NSTEMI. Percutaneous coronary intervention was performed in the same percentage of STEMI (84.6%) and NSTEMI (84.8%) patients, regardless of SARS-CoV-2 infection, but no-reflow (19.2% vs 3.3%; P < 0.001) was greater in SARS-CoV-2 patients. In-hospital death occurred in 7 SARS-CoV-2 patients (5 from cardiac cause) and was higher compared with noninfected patients (26.9% vs 6.2%; P < 0.001). CONCLUSIONS: In this registry, ACS in SARS-CoV-2 patients presented with high a percentage of cardiac arrest on admission, high incidence of no-reflow, and high in-hospital mortality.

CONTEXTE: Notre étude avait pour but d'établir les caractéristiques cliniques et les résultats de patients infectés ou non par le SRAS-CoV-2 qui ont été orientés en raison d'un syndrome coronarien aigu (SCA) pendant la phase aiguë de la pandémie en France. MÉTHODOLOGIE: Nous avons inclus dans l'étude tous les patients consécutifs qui ont présenté un infarctus du myocarde avec sus-décalage du segment ST (STEMI) ou sans sus-décalage du segment ST (NSTEMI) au cours des 3 premières semaines d'avril 2020 et qui ont été orientés vers 5 hôpitaux universitaires (situés à Paris, ainsi que dans le sud et le nord de la France), tous en mesure de réaliser des interventions co-ronariennes percutanées primaires. RÉSULTATS: L'étude comprenait 237 patients (âge : 67 ± 14 ans; proportion d'hommes : 69 %); 116 (49 %) présentaient un STEMI et 121 (51 %), un NSTEMI. La prévalence d'un SCA associé à une infection par le SRAS-CoV-2 s'établissait à 11 % (n = 26), et 11 patients étaient en hypoxémie grave (nécessitant une ventilation artificielle ou l'administration d'oxygène par voie nasale à un débit de plus de 6 l/min) à leur arrivée. Les patients présentaient des antécédents médicaux et des facteurs de risque comparables, à l'exception du fait que la prévalence du diabète était plus élevée chez les patients infectés par le SRAS-CoV-2 (53,8 % vs 25,6 %; p = 0,003). Ces derniers avaient plus souvent subi un arrêt cardiaque à leur admission (26,9 % vs 6,6 %; p < 0,001). Chez les patients infectés par le SRAS-CoV-2, une coronaropathie importante et une occlusion de l'artère coupable ont été observées chez respectivement 92 % et 69,4 % des patients présentant un STEMI, et chez 50 % et 15,5 % des patients présentant un NSTEMI. Une intervention coronarienne percutanée a été effectuée dans les mêmes proportions chez les patients subissant un STEMI (84,6 %) que chez ceux présentant un NSTEMI (84,8 %), sans égard à la présence ou à l'absence d'une infection par le SRAS-CoV-2, mais les cas de non-reperfusion (no-reflow) ont été plus fréquents chez les patients infectés que chez les autres patients (19,2 % et 3,3 %, respectivement; p < 0,001). Sept patients infectés par le SRAS-CoV-2 sont morts à l'hôpital (5 de cause cardiaque), ce qui représente un taux de mortalité plus élevé que chez les patients non infectés (26,9 % vs 6,2 %; p < 0,001). CONCLUSIONS: Dans le cadre de cette étude, le SCA survenu chez les patients infectés par le SRAS-CoV-2 était associé à un fort pourcentage d'arrêt cardiaque à l'admission, à une fréquence élevée de cas de non-reperfusion et à un taux élevé de mortalité hospitalière.

Multimarker approach including CRP, sST2 and GDF-15 for prognostic stratification in stable heart failure.

AIMS: Inflammation and cardiac remodelling are common and synergistic pathways in heart failure (HF). Emerging biomarkers such as soluble suppression of tumorigenicity 2 (sST2) and growth differentiation factor-15 (GDF-15), which are linked to inflammation and fibrosis process, have been proposed as prognosis factors. However, their potential additive values remain poorly investigated. METHODS AND RESULTS: Here, we aimed at evaluating inflammatory and remodelling biomarkers to predict both short-term and long-term mortality in a population with chronic HF in comparison with other classical clinical or biological markers (i.e. N terminal pro brain natriuretic peptide, hs-cTnT, C-reactive protein) alone or using meta-analysis global group in chronic HF risk score in a cohort of 182 patients followed during 80 months (interquartile range: 12.3-90.0). Proportional hazard assumption does not hold for sST2 and C-reactive protein, and follow-up was split into short term (less than 1 year), midterm (between 1 and 5 years), and long term (after 5 years). In univariate analysis, C-reactive protein and sST2 were predictive of short-term mortality but not of middle term and long term whereas GDF-15 was predictive of short and mid-term but not of long-term mortality. In a multivariate model after adjustment for meta-analysis global group in chronic HF score including the three markers, only sST2 was predictive of short-term mortality (P = 0.0225), and only GDF-15 was predictive of middle term mortality (P = 0.0375). None of the markers was predictive of long-term mortality. CONCLUSIONS: Our results demonstrate that both sST2 and GDF-15 significantly improve the prognosis evaluation of HF patients and suggest that the value of GDF-15 is more sustained overtime and could predict middle term events.

One train may hide another: Acute cardiovascular diseases could be neglected because of the COVID-19 pandemic.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is likely to have significant implications for the cardiovascular care of patients. In most countries, containment has already started (on 17 March 2020 in France), and self-quarantine and social distancing are reducing viral contamination and saving lives. However, these considerations may only be the tip of the iceberg; most resources are dedicated to the struggle against COVID-19, and this unprecedented situation may compromise the management of patients admitted with cardiovascular conditions. AIM: We aimed to assess the effect of COVID-19 containment measures on cardiovascular admissions in France. METHODS: We asked nine major cardiology centres to give us an overview of admissions to their nine intensive cardiac care units for acute myocardial infarction or acute heart failure, before and after containment measures. RESULTS: Before containment (02-16 March 2020), the nine participating intensive cardiac care units admitted 4.8±1.6 patients per day, versus 2.6±1.5 after containment (17-22 March 2020) (rank-sum test P=0.0006). CONCLUSIONS: We confirm here, for the first time, a dramatic drop in the number of cardiovascular admissions after the establishment of containment. Many hypotheses might explain this phenomenon, but we feel it is time raise the alarm about the risk for patients presenting with acute cardiovascular disease, who may suffer from lack of attention, leading to severe consequences (an increase in the number of ambulatory myocardial infarctions, mechanical complications of myocardial infarction leading to an increase in the number of cardiac arrests, unexplained deaths, heart failure, etc.). Similar consequences can be feared for all acute situations, beyond the cardiovascular disease setting.

STADE-HF (sST2 As a help for management of HF): a pilot study.

AIMS: Biomarkers are not recommended until now to guide the management of patients with heart failure (HF). Soluble suppression of tumorigenicity 2 (sST2) appears as a promising biomarker. The current study considered pre-discharged sST2 values as a guide for medical management in patients admitted for acute HF decompensation, in an attempt to reduce hospital readmission. METHODS AND RESULTS: STADE-HF was a blinded prospective randomized controlled trial and included 123 patients admitted for acute HF. They were randomized into the usual treatment group (unknown sST2 level) or the interventional treatment group, for whom sST2 level was known and used on Day 4 of hospitalization to guide the treatment. The primary endpoint was the readmission rate for any cause at 1 month. It occurred in 10 patients (19%) in the usual group and 18 (32%) in the sST2 group without statistical difference (P = 0.11). Post hoc analysis in the whole group shows that the mean duration of hospitalization was lower in patients with low sST2 (<37 ng/mL) at admission vs. high sST2 (8.5 ± 9.5 vs. 14.8 ± 14.9 days, respectively, P = 0.003). In addition, a decrease in sST2 greater than 18% is significantly associated with a lower readmission rate. CONCLUSIONS: Soluble suppression of tumorigenicity 2-guided therapy over a short period of time does not reduce readmissions. However, sST2 was clearly associated with duration of hospitalization, and the decrease in sST2 was associated with decreased rehospitalizations. Long-term outcome using sST2-guided therapy deserves further investigations.

Low-dose colchicine prevents sympathetic denervation after myocardial ischemia-reperfusion: a new potential protective mechanism.

PURPOSE: To evaluate the impact of colchicine on sympathetic denervation after acute myocardial infarction (AMI). MATERIALS & METHODS: Ischemia/Reperfusion was induced in C57BL/6J male mice. Left coronary artery was ligated during 45 min followed by reperfusion. 400 µg/kg of colchicine or the placebo was administrated intraperitoneally 15 min before the reperfusion. RESULTS: Colchicine treatment significantly improved heart rate variability index after AMI. Colchicine prevented sympathetic denervation in the remote area (p = 0.04) but not in the scar area (p = 0.70). CONCLUSION: These results suggest promising protective pathway of colchicine after AMI.