Colchicine in acute myocardial infarction: cardiovascular events at 1-year follow up.

OBJECTIVE: In the COVERT-MI randomised placebo-controlled trial, oral administration of high-dose colchicine at the time of reperfusion and for 5 days in acute ST-elevated myocardial infarction did not reduce infarct size but was associated with a significant increase in left ventricular thrombus (LVT) in comparison to placebo. We aimed to assess the 1-year clinical outcomes of the study population. METHODS: This study is a follow-up analysis of the COVERT-MI study on prespecified secondary clinical endpoints at 1 year. The primary endpoint of this study was a composite of major adverse cardiovascular events (MACEs), including all-cause death, acute coronary syndromes, heart failure events, ischaemic strokes, sustained ventricular arrhythmias and acute kidney injury at 1-year follow-up. The quality of life (QOL) and the drug therapy prescription were also assessed. RESULTS: At 1 year, 192 patients (101 patients in the colchicine group, 91 in the placebo group) were followed up. Seventy-six (39.6%) MACEs were reported in the study population. There was no significant difference regarding the number of MACEs between groups: 36 (35.6%) in the colchicine group and 40 (44.1%) in the placebo group (p=0.3). There were no differences in the occurrence of ischaemic strokes between the colchicine group and the control group (3 (3%) vs 2 (2.2%), respectively, p=0.99). There was a trend towards fewer heart failure events in the colchicine group compared with the placebo group (12 (11.9%) vs 18 (19.8%), p=0.20). There was no significant difference in QOL scores at 1 year (75.8±15.7 vs 72.7±16.2 respectively, p=0.18). CONCLUSIONS: There was no significant difference between the colchicine and placebo groups at 1 year regarding MACEs, especially concerning deaths or ischaemic strokes. No excess of ischaemic adverse events was observed despite the initial increase in LVT in the colchicine group. TRIAL REGISTRATION NUMBER: NCT0315681.

Mid-term pulmonary sequelae after hospitalisation for COVID-19: The French SISCOVID cohort.

BACKGROUND: Even though COVID-19 clinical features, pathogenesis, complications, and therapeutic options have been largely described in the literature, long-term consequences in patients remain poorly known. METHODS: The French, multicentre, non-interventional SISCOVID study evaluated lung impairment three (M3) and six months (M6) after hospital discharge in patients recovered from COVID-19. Evaluation was based on clinical examination, pulmonary function tests, and chest computed tomography (CT-scan). RESULTS: Of the 320 included patients (mean age: 61 years; men: 64.1%), 205 had had a severe form of COVID-19, being hospitalised in an intensive care unit (ICU), and requiring high flow nasal cannula, non-invasive ventilation, or invasive mechanical ventilation. At M6, 54.1% of included patients had persistent dyspnoea (mMRC score ≥1), 20.1% severe impairment in gas diffusing capacity (DLCO <60% pred.), 21.6% restrictive ventilatory pattern (total lung capacity <80% pred.), and 40% a fibrotic-like pattern at CT-scan. Fibrotic-like pattern and restrictive ventilatory pattern were significantly more frequent in patients recovered from severe than non-severe COVID-19. Improved functional and radiological outcomes were observed between M3 and M6. At M6, age was an independent risk factor for severe DLco impairment and fibrotic-like pattern and severe COVID-19 form was independent risk factor for restrictive ventilatory profile and fibrotic-like pattern. CONCLUSION: Six months after discharge, patients hospitalised for COVID-19, especially those recovered from a severe form of COVID-19, frequently presented persistent dyspnoea, lung function impairment, and persistent fibrotic-like pattern, confirming the need for long-term post-discharge follow-up in these patients and for further studies to better understand long-term COVID-19 lung impairment.

Effect of Colchicine on Myocardial Injury in Acute Myocardial Infarction.

BACKGROUND: Inflammation is a key factor of myocardial damage in reperfused ST-segment-elevation myocardial infarction. We hypothesized that colchicine, a potent anti-inflammatory agent, may reduce infarct size (IS) and left ventricular (LV) remodeling at the acute phase of ST-segment-elevation myocardial infarction. METHODS: In this double-blind multicenter trial, we randomly assigned patients admitted for a first episode of ST-segment-elevation myocardial infarction referred for primary percutaneous coronary intervention to receive oral colchicine (2-mg loading dose followed by 0.5 mg twice a day) or matching placebo from admission to day 5. The primary efficacy outcome was IS determined by cardiac magnetic resonance imaging at 5 days. The relative LV end-diastolic volume change at 3 months and IS at 3 months assessed by cardiac magnetic resonance imaging were among the secondary outcomes. RESULTS: We enrolled 192 patients, 101 in the colchicine group and 91 in the control group. At 5 days, the gadolinium enhancement-defined IS did not differ between the colchicine and placebo groups with a mean of 26 interquartile range (IQR) [16-44] versus 28.4 IQR [14-40] g of LV mass, respectively (P=0.87). At 3 months follow-up, there was no significant difference in LV remodeling between the colchicine and placebo groups with a +2.4% (IQR, -8.3% to 11.1%) versus -1.1% (IQR, -8.0% to 9.9%) change in LV end-diastolic volume (P=0.49). Infarct size at 3 months was also not significantly different between the colchicine and placebo groups (17 IQR [10-28] versus 18 IQR [10-27] g of LV mass, respectively; P=0.92). The incidence of gastrointestinal adverse events during the treatment period was greater with colchicine than with placebo (34% versus 11%, respectively; P=0.0002). CONCLUSIONS: In this randomized, placebo-controlled trial, oral administration of high-dose colchicine at the time of reperfusion and for 5 days did not reduce IS assessed by cardiac magnetic resonance imaging. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03156816.

Colchicine for Left Ventricular Infarct Size Reduction in Acute Myocardial Infarction: A Phase II, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Study Protocol - The COVERT-MI Study.

Inflammatory processes have been identified as key mediators of ischemia-reperfusion injury in ST-segment elevation myocardial infarction (STEMI). They add damage to the myocardium and are associated with clinical adverse events (heart failure and cardiovascular death) and poor myocardial recovery. Colchicine is a well-known alkaloid with potent anti-inflammatory properties. In a proof-of-concept phase II trial, colchicine has been associated with a significant 50% reduction of infarct size (assessed by creatine kinase levels) in comparison to placebo in acute STEMI patients referred for primary percutaneous coronary intervention (PPCI). The Colchicine in STEMI Patients Study (COVERT-MI) is an ongoing confirmative prospective, multicenter, randomized, double-blind trial testing whether a short course oral treatment with colchicine versus placebo decreases myocardial injury in patients presenting with STEMI referred for PPCI. Adult patients, with a first STEMI episode and an initial TIMI flow ≤1, referred for PPCI, will be randomized (n = 194) in a 1:1 ratio to receive an oral bolus of colchicine of 2 mg followed by 0.5 mg b.i.d. treatment during 5 days or matching placebo. The primary endpoint will be the reduction in infarct size as assessed by cardiac magnetic resonance at 5 ± 2 days between both groups. The main secondary endpoints will be tested between groups in hierarchical order with left ventricular ejection fraction at 5 days, microvascular obstruction presence at 5 days, and absolute adverse left ventricular remodeling between 5 days and 3 months. This academic study is being financed by a grant from the French Ministry of Health (PHRCN-16-0357). Results from this study will contribute to a better understanding of the complex pathophysiology underlying myocardial injury after STEMI. The present study describes the rationale, design, and methods of the trial.

Multiple Arterial Thrombosis in a 78-Year-Old Patient: Catastrophic Thrombotic Syndrome in COVID-19.

We describe a patient with coronavirus disease 2019 (COVID-19) and multiple concomitant thromboses occurring on the 9th day of hospital stay. Thromboses were found in distinct zones of the aorta, as well as in the renal, humeral, and pulmonary arteries. The extensive biological workup performed following this catastrophic thrombotic syndrome found no evidence for underlying prothrombotic disease. In light of current evidence regarding endothelium abnormalities related to COVID-19, this extreme case of catastrophic thrombotic syndrome suggests that COVID-19 can induce severe arterial thrombosis following intense endothelial activation.

Nous décrivons le cas d'un patient atteint de la maladie à coronavirus 2019 (COVID-19) et présentant de multiples thromboses concomitantes survenant au 9e jour d'hospitalisation. Les thromboses ont été identifiées dans des zones distinctes de l'aorte, ainsi que dans les artères rénales, humérales et pulmonaires. Un examen biologique approfondi effectué à la suite de ce syndrome thrombotique catastrophique n'a révélé aucun signe de maladie prothrombotique sous-jacente. À la lumière de ces éléments concernant les anomalies de l'endothélium liées à la COVID-19, ce cas extrême de syndrome thrombotique catastrophique suggère que la COVID-19 peut induire une thrombose artérielle sévère suite à une activation endothéliale intense.

Coronary artery fenestration as rescue management of intramural haematoma with luminal compression.

Conservative management is the first-line treatment for spontaneous coronary artery dissection (SCAD) with stable haemodynamic status and thrombolysis in myocardial infarction three flow on angiography. However, in a few very specific patients, recurrent ischemia, or haemodynamic instability necessitates revascularization. Here, we describe a case of successful optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI) with a cutting balloon. We performed fenestration at multiple decompression sites prior to stenting in an intramural haematoma with luminal compression. Rescue management of SCAD with luminal compression is a critical issue, because SCAD is an emergent clinical condition affecting young patients with a severe prognosis. To our knowledge, there are no large published series evaluating procedural success rates and long-term follow-up of this technique.

The Importance of Apneic Events in Obstructive Sleep Apnea Associated with Acute Coronary Syndrome.

BACKGROUND: Obstructive sleep apnea (OSA) is a potential cardiovascular risk factor. However, there is currently no prominent screening strategy for its diagnosis in patients with acute coronary syndrome (ACS). The aim of this study was to establish the impact of apneic events in case of OSA associated with ACS. METHODS: Between January 1st and June 30th, fifty-three subjects with ACS (first acute myocardial infarction) were prospectively evaluated for OSA. Each patient was evaluated by polysomnography (PSG) two months after the ACS. RESULTS: Mean age of 59±9,6 years, 81,1% males, BMI at 28,5±4,2 kg/m2, neck circumference of 42,5±12,6 cm, and waist circumference os 102,5±16,5 cm. The majority of patients (73,6%) had moderate to severe OSA (apnea-hypopnea index (AHI) ≥ 15/h and arousal index ≥ 10/h). We defined the apneic coefficient (AC) as the ratio between apnea index (AI) and AHI. We chose as cut-off the median value of apnea coefficient in our population which was at 37%. The patients with a higher AC (AC ≥ 37% versus AC < 37%) had higher levels of Troponin-I (63,4±63,2 versus 29,7±36,1 ng/mL, p=0,016), higher levels of NT-proBNP (1879,8±2141,8 versus 480±621,3 pg/mL, p=0,001), higher SYNTAX score (15,8±11,5 versus 10,2±5,9, p=0,049), and lower left ventricle ejection fraction (LVEF 53,3±11,4 versus 59,4±6,4%, p=0,023) and were more likely to have a STEMI (21 patients (77,7%) vesus 14 patients (53,8%), p=0,031). CONCLUSION: An apneic coefficient (AI/AHI) ≥ 37% is correlated with more severe cardiac impairment, as well as higher hypoxemia and arousal index.

A Potentially Lethal Dysfunction of a Subcutaneous Implantable Cardiac Defibrillator: "The Phantom Menace"?

In this article we describe, to our knowledge, the first case of a potentially lethal dysfunction of a subcutaneous implantable cardioverter-defibrillator (S-ICD). A 70-year-old patient underwent primary S-ICD implantation. Nine months after, communication could not be established with the device. Chest radiography revealed that the lead had moved and wrapped around the generator. After equipment extraction, we observed the lead wound around the sagittal axis of the generator. A burn mark with melted metal was found inside the generator. Our hypothesis is an electric arc occurred between the retracted lead and the generator. This could be the first reported Reel syndrome secondary to S-ICD implantation.

SOFA score to assess the severity of the post-cardiac arrest syndrome.

AIM OF THE STUDY: The aim of the study was to assess the prognostic impact of organ failures at ICU admission after out-of-hospital cardiac arrest (CA) according to the SOFA score. METHODS: We performed a retrospective analysis of a prospective cohort of all adult patients admitted to a 15-bed medical ICU in a university-affiliated hospital after an out-of-hospital CA. In addition to demographic and clinical data, initial illness severity was measured using the SOFA score. Outcomes (mortality and neurological prognosis) were also collected at day 28 and one year. RESULTS: A total of 304 patients (age: 66±16 years, male: 55%) were admitted for post-CA management. An initial nonshockable cardiac rhythm was recorded in 274 (90%) cases. At admission, SOFA score averaged 9.8±3.1 for the entire cohort (8.1±3.3 for day 28 survivors versus 10.1±3.1 for non-survivors, p<0.001). At day 1, SOFA remained significantly (p<0.001) higher in nonsurvivors (9.8±3.8) when compared to survivors (6.5±4.1). Death occurred in 269 (88%) and 275 (90%) patients within the 28-day and one-year period, respectively. Neurological outcome at one year was favorable (CPC score 1-2) in 23patients (8%). Multivariate analysis identified the SOFA score at admission as independently associated with mortality at day28 (OR per point of SOFA score 1.17; 95% CI 1.01-1.35; p=0.03). CONCLUSIONS: In the present study, early organ failures, as assessed by the SOFA score at ICU admission, were independently associated with day 28 mortality. SOFA score may help clinicians objectively evaluate the severity of the post-CA syndrome.

Bioelectrical impedance analysis for heart failure diagnosis in the ED.

INTRODUCTION: The aim of this study was to evaluate bioimpedance vector analysis (BIVA) for the diagnosis of acute heart failure (AHF) in patients presenting with acute dyspnea to the emergency department (ED). METHODS: Patients with acute dyspnea presenting to the ED were prospectively enrolled. Four parameters were assessed: resistance (R), reactance (Ra), total body water (TBW), and extracellular body water (EBW). Brain natriuretic peptide (BNP) measures and cardiac ultrasound studies were performed in all patients at admission. Patients were classified into AHF and non-AHF groups retrospectively by expert cardiologists. RESULTS: Seventy-seven patients (39 men; age, 68±14years; weight, 79.8±20.6 kg) were included. Of the 4 BIVA parameters, Ra was significantly lower in the AHF compared to non-AHF group (32.7±14.3 vs 45.4±19.7; P<.001). Brain natriuretic peptide levels were significantly higher in the AHF group (1050.3±989 vs 148.7±181.1ng/L; P<.001). Reactance levels were significantly correlated to BNP levels (r=-0.5; P<.001). Patients with different mitral valve Doppler profiles (E/e'≤8, E/e' ≥9 and <15, and E/e'≥15) had significant differences in Ra values (47.9±19.9, 34.7±19.4, and 31.2±11.7, respectively; P=.003). Overall, the sensitivity of BIVA for AHF diagnosis with a Ra cutoff at 39Ω was 67% with a specificity of 76% and an area under the curve at 0.76. However, Ra did not significantly improve the area under the curve of BNP for the diagnosis of AHF (P=not significant). CONCLUSION: In a population of patients presenting to the ED with dyspnea, BIVA was significantly related to the AHF status but did not improve the diagnostic performance for AHF in addition to BNP alone.

Myocardial biomarkers and delayed enhanced cardiac magnetic resonance relationship in clinically suspected myocarditis and insight on clinical outcome.

AIMS: The relationship of cardiac magnetic resonance (CMR) late gadolinium enhancement (LGE) with myocardial biomarkers and markers of inflammation in acute viral myocarditis is not clearly defined. We assessed the relationship of LGE with myocardial and inflammatory biomarkers measured during the acute phase of myocarditis and their predictive value on clinical outcome. METHODS: Patients with first clinical episode of acute viral myocarditis and complete CMR study, including cine and LGE images, were included. The peak values of troponin I, creatine kinase, C-reactive protein value at admission and LGE extent were reported for each case. A 29-month clinical follow-up was performed, and cardiac symptoms and adverse cardiac events (all-cause death, heart transplant, hospitalization for heart failure) were reported. RESULTS: Forty-one patients (39 ±â€Š15 years and 78% men) were included. Median LGE extent was 13% [interquartile range (IQR) (9%, 19%)] of left-ventricular mass and mean left-ventricular ejection fraction was 56 ±â€Š11%. There was a significant correlation between peak troponin I and LGE extent (r = 0.51, P < 0.001), and between peak creatine kinase and LGE extent (r = 0.66, P < 0.001). There was no correlation between C-reactive protein at admission and LGE extent (r = 0.27, P = 0.09). At follow-up, eight (20%) patients had an adverse clinical event. LGE extent was significantly associated with a worse New York Heart Association status at follow-up [odds ratio (OR) 1.21, 95% confidence interval (CI) 1.07, 1.37, P = 0.002]. After adjustment for left-ventricular ejection fraction, age and clinical presentation category, LGE extent remained an independent predictor of cardiovascular events (hazard ratio 1.42; 95% CI 1.05, 1.95, P = 0.027). CONCLUSIONS: LGE extent on CMR studies is significantly correlated to biomarkers of myocardial injury in patients with acute viral myocarditis, and is a significant independent predictor of adverse cardiovascular outcome.

In-hospital heart rate turbulence and microvolt T-wave alternans abnormalities for prediction of early life-threatening ventricular arrhythmia after acute myocardial infarction.

BACKGROUND: In the setting of primary prevention, most implantable cardiac defibrillators (ICD) are implanted more than 6 months after acute myocardial infarction (AMI). Abnormal heart rate turbulence (HRT) and T-wave alternans (TWA) are predictors of long-term sudden cardiac death (SCD). We intended to assess the predictive value of HRT and TWA for early post-AMI SCD and life-threatening ventricular arrhythmias (VA). METHODS: One hundred ninety-nine consecutive patients with AMI were prospectively included (age 61.7 years, LV ejection fraction 45%). One hundred eighty-three patients (92%) underwent percutaneous coronary intervention. We assessed HRT using turbulence slope (TS), turbulence onset (TO), and TWA on channels 1 and 2 (TWA1 and TWA2) using the modified moving average method. Predictive performance for SCD/VA was assessed by area under the receiver operating curve characteristic (ROC-AUC). RESULTS: Within 6 months after AMI, 2 patients (1%) developed life-threatening VA and 3 (1.5%) experienced SCD. TO and TWA1 had poor ROC-AUC (both 0.64) whereas TS and TWA2 failed to show any predictive performance (ROC-AUC 0.48 and 0.57, respectively). When combining TO and TWA1, ROC-AUC increased to 0.80. Importantly, when considering the subset of patients with a LV ejection fraction ≤40%, the combined variable of TO and TWA1 remained strongly predictive of a short-term event (ROC-AUC 0.86). CONCLUSIONS: Combined assessment of HRT and TWA showed a high predictive performance for SCD or life-threatening VA within 6 months after AMI. This combined Holter ECG index could be useful to identify high-risk patients who might benefit from early ICD implantation.

Therapeutic management changes and mortality rates over 30 years in ventricular septal rupture complicating acute myocardial infarction.

Recent studies have shown that the decrease in ventricular septal rupture (VSR) incidence after acute myocardial infarction is related to the improvement of reperfusion strategies. Our main objective was to explore the influence of therapeutic management changes on post-infarct VSR patient outcomes in a single reference center over a period of 30 years. We analyzed therapeutic management strategies and mortality rates in 228 patients with VSR after acute myocardial infarction admitted from 1981 to 2010. Patients were classified in 3 successive decades. There were no significant differences in clinical characteristics of patients with VSR at admission among those decades. Overall, surgery was performed in 159 patients (71.9%), primary transcatheter VSR closure was attempted in 5 patients (2.2%), and 64 patients (27.6%) were managed medically. Independent predictors of in-hospital mortality were VSR surgical repair (odds ratio [OR] 0.22, 95% confidence interval [CI] 0.1 to 0.7, p = 0.008), cardiogenic shock (OR 6.06, 95% CI 2.8 to 13.1, p <0.0001), and Killip class on admission (OR 1.75, 95% CI 1.1 to 9.9, p = 0.02). We found a significant 1-year mortality reduction between the first and second decades (hazard ratio 0.48, 95% CI 0.28 to 0.80; p = 0.005), with no significant change in the last decade (p = 0.2). This change was related to a systematic referral to surgical repair and shorter delays to VSR surgery (5.2 ± 6.3 vs 1.9 ± 3.2 days from first to second decade; p = 0.012). In conclusion, surgical repair remains the only significant efficient therapy to reduce mortality in patients with VSR (p <10(-3)). In-hospital prognosis remains disappointing. This contrasts with the favorable long-term outcome of patients who survive the perioperative period and are discharged from hospital.

Pulseless electrical activity after myocardial infarction: not always a left ventricular free wall rupture.

Pulseless electrical activity (PEA) after acute myocardial infarction is classically caused by ventricular free wall rupture. We report the case of a 76-year-old woman who presented a cardiac arrest with PEA 5 days after an embolic acute myocardial infarction. Transthoracic echocardiogram showed a massive mitral regurgitation due to posterior papillary muscle rupture. This case demonstrates that other causes potentially treatable than cardiac tamponade must be sought in patients with PEA after myocardial infarction.

Preliminary experience with Impella Recover(®) LP5.0 in nine patients with cardiogenic shock: a new circulatory support system in the intensive cardiac care unit.

AIM: Cardiogenic shock is associated with high mortality. We report our experience with the short-term left ventricular axial pump Impella LP5.0 in nine patients with severe ischaemic heart failure. METHODS: Six patients (group 1) presented with cardiogenic shock at the acute phase of an ST elevation myocardial infarction. Three patients (group 2) had severe ischaemic cardiomyopathy with temporary contra-indication to LVAD or transplantation. We measured haemodynamic and metabolic variables up to 96hours and recorded morbidity, mechanical pump failures, and mortality up to one year postimplantation. RESULTS: In all patients the Impella LP5.0 was safely placed through the right subclavian artery. Cardiac power output increased from 0.64 (0.07) W to 0.94 (0.44) W and 1.02 (0.30) W at 24 and 72hours, respectively. The Impella LP5.0 remained in place for 12 (7.2) days. In group 1, five patients were in INTERMACS Profile 3 at the time of pump insertion. Three could be weaned and survived. One patient in INTERMACS Profile 1 died of intractable heart failure within hours. In group 2, two of three patients underwent heart transplantation. Haemorrhage requiring transfusions was observed in four patients but only one case was directly related to the Impella LP5.0. CONCLUSION: Left ventricular assistance with the Impella LP5.0 appears to be well tolerated. It may be especially useful in patients with acute myocardial infarction complicated by cardiogenic shock who achieve INTERMACS Profile 3 with initial treatment.