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.

The admission level of CRP during cardiogenic shock is a strong independent risk marker of mortality.

Inflammatory processes are involved not only in coronary artery disease but also in heart failure (HF). Cardiogenic shock (CS) and septic shock are classically distinct although intricate relationships are frequent in daily practice. The impact of admission inflammation in patients with CS is largely unknown. FRENSHOCK is a prospective registry including 772 CS patients from 49 centers. One-month and one-year mortalities were analyzed according to the level of C-reactive protein (CRP) at admission, adjusted on independent predictive factors. Within 406 patients included, 72.7% were male, and the mean age was 67.4 y ± 14.7. Four groups were defined, depending on the quartiles of CRP at admission. Q1 with a CRP < 8 mg/L, Q2: CRP was 8-28 mg/L, Q3: CRP was > 28-69 mg/L, and Q4: CRP was > 69 mg/L. The four groups did not differ regarding main baseline characteristics. However, group Q4 received more often antibiotics in 47.5%, norepinephrine in 66.3%, and needed more frequently respiratory support and renal replacement therapy. Whether at 1 month (Ptrend = 0.01) or 1 year (Ptrend < 0.01), a strong significant trend towards increased all-cause mortality was observed across CRP quartiles. Specifically, compared to the Q1 group, Q4 patients demonstrated a 2.2-fold higher mortality rate at 1-month (95% CI 1.23-3.97, p < 0.01), which persisted at 1-year, with a 2.14-fold increase in events (95% CI 1.43-3.22, p < 0.01). Admission CRP level is a strong independent predictor of mortality at 1 month and 1-year in CS. Specific approaches need to be developed to identify accurately patients in whom inflammatory processes are excessive and harmful, paving the way for innovative approaches in patients admitted for CS.NCT02703038.

PRADOC: A Multicenter Randomized Controlled Trial to Assess the Efficiency of PRADO-IC, a Nationwide Pragmatic Transition Care Management Plan for Hospitalized Patients With Heart Failure in France.

BACKGROUND: The PRADO-IC (Programme de Retour à Domicile après une Insuffisance Cardiaque) is a transition care program designed to improve the coordination of care between hospital and home that was generalized in France in 2014. The PRADO-IC consists of an administrative assistant who visits patients during hospitalization to schedule follow-up visits. The aim of the present study was to evaluate the PRADO-IC program based on the hypotheses provided by health authorities. METHODS AND RESULTS: The PRADOC study is a multicenter, controlled, randomized, open-label, mixed-method trial of the transition program PRADO-IC versus usual management in patients hospitalized with heart failure (standard of care group; NCT03396081). A total of 404 patients were recruited between April 2018 and May 2021. The mean patient age was 75 years (±12 years) in both groups. The 2 groups were well balanced regarding severity indices. At discharge, patients homogeneously received the recommended drugs. There was no difference between groups regarding hospitalizations for acute heart failure at 1 year, with 24.60% in the standard of care group and 25.40% in the PRADO-IC group during the year following the index hospitalization (hazard ratio, 1.04 [95% CI, 0.69-1.56]; P=0.85) or cardiovascular mortality (hazard ratio, 0.67 [95% CI, 0.34-1.31]; P=0.24). CONCLUSIONS: The PRADO-IC has not significantly improved clinical outcomes, though a trend toward reduced cardiovascular mortality is evident. These results will help in understanding how transitional care programs remain to be integrated in pathways of current patients, including telemonitoring, and to better tailor individualized approaches. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT03396081.

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.

Wearable Cardioverter Defibrillator Shortens the Lengths of Stay in Patients with Left Ventricular Dysfunction after Myocardial Infarction: A Single-Centre Real-World Experience.

The wearable cardioverter defibrillator (WCD) has been proven to be effective in preventing sudden cardiac death (SCD) in patients soon after acute myocardial infarction (AMI) and left ventricular ejection fraction (LVEF) ≤35%. The aim of this study was to assess whether a WCD may shorten the length of an initial hospital stay (total length, days in the intensive care unit (ICU) and in the acute cardiac care unit (ACCU)) among these patients. This was a single-centre, retrospective observational study of patients referred for the management of SCD risk post-AMI and LVEF ≤35%, in a tertiary care hospital. The clinical characteristics and length of index hospitalization of the group of patients discharged, with or without WCD, were compared. A propensity score analysis was performed, then weighted regression models were conducted. A total of 101 patients in the WCD group and 29 in the control group were enrolled in the analysis. In the weighted regression models, WCD significantly reduced the days spent in ACCU (p < 0.001). WCD patients had significantly fewer days spent in ACCU (5.5 ± 2.6 vs. 8.4 ± 12.8 days, p < 0.001) and shorter hospitalizations (10.2 ± 5.7 vs. 13.4 ± 17.6 days, p = 0.005), compared with the control group. It was concluded that the WCD appears to reduce the total length of hospitalization and lengths of stay in ACCU for patients post-AMI and with left ventricular dysfunction.

One-Year Follow-Up of Patients Admitted for Emergency Coronary Angiography after Resuscitated Cardiac Arrest.

(1) Background: Despite the improvement of the in-hospital survival rate after aborted sudden cardiac death (SCD), cerebral anoxia may have severe neurologic consequences and may impair long-term outcome and quality of life of surviving patients. The aim of this study was to assess neurological outcomes at one year after resuscitated cardiac arrest; (2) Methods: This prospective, observational, and multicentre study included patients >18 yo admitted in the catheterisation laboratory for coronary angiography after aborted SCD between 1 May 2018 and 31 May 2020. Only patients who were discharged alive from hospital were evaluated. The primary endpoint was survival without neurological sequelae at one-year follow-up defined by a cerebral performance category (CPC) of one or two. Secondary end points included all-cause mortality, New York Heart Association (NYHA) functional class, neurologic evaluation at discharge, three-month and one-year follow-up using the CPC scale, and quality of life at 1 year using the Quality of Life after Brain Injury (QOLIBRI) questionnaire; (3) Results: Among 143 patients admitted for SCD within the study period, 61 (42.7%) were discharged alive from hospital, among whom 55 (90.1%) completed the one-year follow-up. No flow and low flow times were 1.9 ± 2.4 min and 16.5 ± 10.4 min, respectively. For 93.4% of the surviving patients, an initial shockable rhythm (n = 57) was observed and acute coronary syndrome was diagnosed in 75.4% of them (n = 46). At 1 year, survival rate without neurologic sequelae was 87.2% (n = 48). Patients with poor outcome were older (69.3 vs. 57.4 yo; p = 0.04) and had lower body mass index (22.4 vs. 26.7; p = 0.013) and a lower initial Left Ventricle Ejection Fraction (LVEF) (32.1% vs. 40.3%; p = 0.046). During follow-up, neurological status improved in 36.8% of patients presenting sequelae at discharge, and overall quality of life was satisfying for 66.7% of patients according to the QOLIBRI questionnaire; (4) Conclusions: Among patients admitted to the catheterisation laboratory for aborted SCD, mainly related to Acute Coronary Syndrom (ACS), less than a half of them were alive at discharge. However, the one-year survival rate without neurological sequelae was high and overall quality of life was good.