Phenotypic clustering of patients hospitalized in intensive cardiac care units: Insights from the ADDICT-ICCU study.

BACKGROUND: Intensive cardiac care units (ICCUs) were created to manage ventricular arrhythmias after acute coronary syndromes, but have diversified to include a more heterogeneous population, the characteristics of which are not well depicted by conventional methods. AIMS: To identify ICCU patient subgroups by phenotypic unsupervised clustering integrating clinical, biological, and echocardiographic data to reveal pathophysiological differences. METHODS: During 7-22 April 2021, we recruited all consecutive patients admitted to ICCUs in 39 centers. The primary outcome was in-hospital major adverse events (MAEs; death, resuscitated cardiac arrest or cardiogenic shock). A cluster analysis was performed using a Kamila algorithm. RESULTS: Of 1499 patients admitted to the ICCU (69.6% male, mean age 63.3±14.9 years), 67 (4.5%) experienced MAEs. Four phenogroups were identified: PG1 (n=535), typically patients with non-ST-segment elevation myocardial infarction; PG2 (n=444), younger smokers with ST-segment elevation myocardial infarction; PG3 (n=273), elderly patients with heart failure with preserved ejection fraction and conduction disturbances; PG4 (n=247), patients with acute heart failure with reduced ejection fraction. Compared to PG1, multivariable analysis revealed a higher risk of MAEs in PG2 (odds ratio [OR] 3.13, 95% confidence interval [CI] 1.16-10.0) and PG3 (OR 3.16, 95% CI 1.02-10.8), with the highest risk in PG4 (OR 20.5, 95% CI 8.7-60.8) (all P<0.05). CONCLUSIONS: Cluster analysis of clinical, biological, and echocardiographic variables identified four phenogroups of patients admitted to the ICCU that were associated with distinct prognostic profiles. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05063097.

Three-Year Outcomes With Fractional Flow Reserve-Guided or Angiography-Guided Multivessel Percutaneous Coronary Intervention for Myocardial Infarction.

BACKGROUND: In patients with multivessel disease with successful primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction, the FLOWER-MI trial (Flow Evaluation to Guide Revascularization in Multivessel ST-Elevation Myocardial Infarction) showed that a fractional flow reserve (FFR)-guided strategy was not superior to an angiography-guided strategy for treatment of noninfarct-related artery lesions regarding the 1-year risk of death from any cause, myocardial infarction, or unplanned hospitalization leading to urgent revascularization. The extension phase of the trial was planned using the same primary outcome to determine whether a difference in outcomes would be observed with a longer follow-up. METHODS: In this multicenter trial, we randomly assigned patients with ST-segment-elevation myocardial infarction and multivessel disease with successful percutaneous coronary intervention of the infarct-related artery to receive complete revascularization guided by either FFR (n=586) or angiography (n=577). RESULTS: After 3 years, a primary outcome event occurred in 52 of 498 patients (9.40%) in the FFR-guided group and in 44 of 502 patients (8.17%) in the angiography-guided group (hazard ratio, 1.19 [95% CI, 0.79-1.77]; P=0.4). Death occurred in 22 patients (4.00%) in the FFR-guided group and in 23 (4.32%) in the angiography-guided group (hazard ratio, 0.96 [95% CI, 0.53-1.71]); nonfatal myocardial infarction in 23 (4.13%) and 14 (2.56%), respectively (hazard ratio, 1.63 [95% CI, 0.84-3.16]); and unplanned hospitalization leading to urgent revascularization in 21 (3.83%) and 18 (3.36%; hazard ratio, 1.15 [95% CI, 0.61-2.16]), respectively. CONCLUSIONS: Although event rates in the trial were lower than expected, in patients with ST-segment-elevation myocardial infarction undergoing complete revascularization, an FFR-guided strategy did not have a significant benefit over an angiography-guided strategy with respect to the risk of death, myocardial infarction, or urgent revascularization up to 3 years. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02943954.

Rationale and design of the FRENch CoHort of myocardial Infarction Evaluation (FRENCHIE) study.

BACKGROUND: Despite major advances in prevention and treatment, cardiovascular diseases - particularly acute myocardial infarction - remain a leading cause of death worldwide and in France. Collecting contemporary data about the characteristics, management and outcomes of patients with acute myocardial infarction in France is important. AIMS: The main objectives are to describe baseline characteristics, contemporary management, in-hospital and long-term outcomes of patients with acute myocardial infarction hospitalized in tertiary care centres in France; secondary objectives are to investigate determinants of prognosis (including periodontal disease and sleep-disordered breathing), to identify gaps between evidence-based recommendations and management and to assess medical care costs for the index hospitalization and during the follow-up period. METHODS: FRENCHIE (FRENch CoHort of myocardial Infarction Evaluation) is an ongoing prospective multicentre observational study (ClinicalTrials.gov Identifier: NCT04050956) enrolling more than 19,000 patients hospitalized for acute myocardial infarction with onset of symptoms within 48hours in 35 participating centres in France since March 2019. Main exclusion criteria are age<18 years, lack of health coverage and procedure-related myocardial infarction (types 4a and 5). Detailed information was collected prospectively, starting at admission, including demographic data, risk factors, medical history and treatments, initial management, with prehospital care pathways and medication doses, and outcomes until hospital discharge. The follow-up period (up to 20 years for each patient) is ensured by linking with the French national health database (Système national des données de santé), and includes information on death, hospital admissions, major clinical events, healthcare consumption (including drug reimbursement) and total healthcare costs. FRENCHIE is also used as a platform for cohort-nested studies - currently three randomized trials and two observational studies. CONCLUSIONS: This nationwide large contemporary cohort with very long-term follow-up will improve knowledge about acute myocardial infarction management and outcomes in France, and provide a useful platform for nested studies and trials.

TAPSE/sPAP prognostic value for In-Hospital Adverse Events in Patients Hospitalized for Acute Coronary Syndrome.

AIMS: Although several studies have shown that the right ventricular to pulmonary artery (RV-PA) coupling, assessed by the ratio between tricuspid annular plane systolic excursion and systolic pulmonary artery pressure (TAPSE/sPAP) using echocardiography, is strongly associated with cardiovascular events, its prognostic value is not established in acute coronary syndrome (ACS). We aimed to assess the in-hospital prognostic value of TAPSE/sPAP among patients hospitalized for ACS in a retrospective analysis from the prospective ADDICT-ICCU study. METHODS AND RESULTS: 481 consecutive patients hospitalized in intensive cardiac care unit (mean age 65±13 years, 73% of male, 46% STEMI) for ACS (either ST-elevation [STEMI] or non-ST-elevation [NSTEMI] myocardial infarction) with TAPSE/sPAP available were included in this prospective French multicentric study (39 centers). The primary outcome was in-hospital major adverse cardiovascular events (MACEs) defined as all-cause death, resuscitated cardiac arrest or cardiogenic shock and occurred in 33 (7%) patients. ROC-curve analysis identified 0.55 mm/mmHg as the best TAPSE/sPAP cut-off to predict in-hospital MACEs. TAPSE/sPAP <0.55 was associated with in-hospital MACEs, even after adjustment with comorbidities (OR:19.1, 95%CI[7.78-54.8]), clinical severity including left ventricular ejection fraction (OR:14.4, 95%CI[5.70-41.7]) and propensity-matched population analysis (OR:22.8, 95%CI[7.83-97.2], all p<0.001). After adjustment, TAPSE/sPAP <0.55 showed the best improvement in model discrimination and reclassification above traditional prognosticators (C-statistic improvement: 0.16; global chi-square improvement: 52.8; LR-test p<0.001) with similar results for both STEMI and NSTEMI subgroups. CONCLUSION: A low RV-PA coupling defined as TAPSE/sPAP ratio <0.55 was independently associated with in-hospital MACEs and provided incremental prognostic value over traditional prognosticators in patients hospitalized for ACS. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05063097.

In-hospital Prognostic Value of TAPSE/sPAP in Patients Hospitalized for Acute Heart Failure.

AIMS: TAPSE/sPAP (tricuspid annular plane systolic excursion over systolic pulmonary artery pressure) assessed by echocardiography appears to be a good noninvasive approach for right ventricular to pulmonary artery coupling assessment. We aimed to assess the in-hospital prognostic value of TAPSE/sPAP among patients hospitalized for acute heart failure (AHF). METHODS AND RESULTS: 333 consecutive patients (mean age 68 ± 14 years, 70% of male, mean LVEF 44 ± 16%) hospitalized for AHF across 39 French cardiology department, with TAPSE/sPAP measured by echocardiography within the 24 first hours of hospitalization were included in this prospective study. The primary outcome was in-hospital major adverse cardiovascular events (MACEs) defined as all-cause death, resuscitated cardiac arrest or cardiogenic shock and occurred in 50 (15%) patients. Using receiver operating characteristics curves analysis, the best TAPSE/sPAP threshold for in-hospital MACEs was 0.40 mm/mmHg. TAPSE/sPAP <0.40 mm/mmHg was independently associated with in-hospital MACEs, even after adjustment with comorbidities (OR:3.75, 95%CI[1.87-7.93], p < 0.001), clinical severity (OR:2.80, 95%CI[1.36-5.95], p = 0.006). Using a 1:1 propensity-matched population, TAPSE/sPAP ratio <0.40 was associated with a higher rate of in-hospital MACEs (OR:2.98, 95%CI[1.53-6.12], p = 0.002). After adjustment, TAPSE/sPAP <0.40 showed the best improvement in model discrimination and reclassification above traditional prognostic factors (C-statistic improvement: 0.05; Chi-2 improvement: 14.4; LR-test p < 0.001). These results were consistent in an external validation cohort of 133 patients. CONCLUSION: TAPSE/sPAP < 0.40 mm/mmHg assessed by an early echocardiography during an AHF episode is independently associated with in-hospital MACEs suggesting enhanced close monitoring and strengthened HF-specific care in these patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05063097.

Profile of patients hospitalized in intensive cardiac care units in France: ADDICT-ICCU registry.

BACKGROUND: Intensive cardiac care units (ICCU) were initially developed to monitor ventricular arrhythmias after myocardial infarction. In recent decades, ICCU have diversified their activities. AIM: To determine the type of patients hospitalized in ICCU in France. METHODS: We analysed the characteristics of patients enrolled in the ADDICT-ICCU registry (NCT05063097), a prospective study of consecutive patients admitted to ICCU in 39 centres throughout France from 7th-22nd April 2021. In-hospital major adverse events (MAE) (death, resuscitated cardiac arrest and cardiogenic shock) were recorded. RESULTS: Among 1499 patients (median age 65 [interquartile range 54-74] years, 69.6% male, 21.7% diabetes mellitus, 64.7% current or previous smokers), 34.9% had a history of coronary artery disease, 11.7% atrial fibrillation and 5.2% cardiomyopathy. The most frequent reason for admission to ICCU was acute coronary syndromes (ACS; 51.5%), acute heart failure (AHF; 14.1%) and unexplained chest pain (6.8%). An invasive procedure was performed in 36.2%. "Advanced" ICCU therapies were required for 19.9% of patients (intravenous diuretics 18.4%, non-invasive ventilation 6.1%, inotropic drugs 2.3%). No invasive procedures or advanced therapies were required in 44.1%. Cardiac computed tomography or magnetic resonance imaging was carried out in 12.3% of patients. The median length of ICCU hospitalization was 2.0 (interquartile range 1.0-4.0) days. The mean rate of MAE was 4.5%, and was highest in patients with AHF (10.4%). CONCLUSIONS: ACS remains the main cause of admissions to ICCU, with most having a low rate of in-hospital MAE. Most patients experience a brief stay in ICCU before being discharged home. AHF is associated with highest death rate and with higher resource consumption.

In-hospital prognosis of acute ST-elevation myocardial infarction in patients with recent recreational drug use.

AIMS: Although recreational drug use may induce ST-elevated myocardial infarction (STEMI), its prevalence in patients hospitalized in intensive cardiac care units (ICCUs), as well as its short-term cardiovascular consequences, remains unknown. We aimed to assess the in-hospital prognosis of STEMI in patients with recreational drug use from the ADDICT-ICCU study. METHODS AND RESULTS: From 7-22 April 2021, recreational drug use was detected prospectively by a systematic urine multidrug test in all consecutive patients admitted for STEMI in 39 ICCUs across France. The primary endpoint was major adverse cardiac events (MACEs) defined by death, resuscitated cardiac arrest, or cardiogenic shock. Among the 325 patients (age 62 ± 13 years, 79% men), 41 (12.6%) had a positive multidrug test (cannabis: 11.1%, opioids: 4.6%, cocaine: 1.2%, 3,4-methylenedioxymethamphetamine: 0.6%). The prevalence increased to 34.0% in patients under 50 years of age. Recreational drug users were more frequently men (93% vs. 77%, p = 0.02), younger (50 ± 12 years vs. 63 ± 13 years, P < 0.001), and more active smokers (78% vs. 34%, P < 0.001). During hospitalization, 17 MACEs occurred (5.2%), including 6 deaths (1.8%), 10 cardiogenic shocks (3.1%), and 7 resuscitated cardiac arrests (2.2%). Major adverse cardiac events (17.1% vs. 3.5%, P < 0.001) and ventricular arrhythmia (9.8% vs. 1.4%, P = 0.01) were more frequent in recreational drug users. Use of recreational drugs was associated with more MACEs after adjustment for comorbidities (odds ratio = 13.1; 95% confidence interval: 3.4-54.6). CONCLUSION: In patients with STEMI, recreational drug use is prevalent, especially in patients under 50 years of age, and is independently associated with an increase of MACEs with more ventricular arrhythmia. TRIAL REGISTRATION: URL: https://clinicaltrials.gov/ct2/show/NCT05063097.

Carbon monoxide and prognosis in smokers hospitalised with acute cardiac events: a multicentre, prospective cohort study.

Background: Smoking cigarettes produces carbon monoxide (CO), which can reduce the oxygen-carrying capacity of the blood. We aimed to determine whether elevated expiratory CO levels would be associated with a worse prognosis in smokers presenting with acute cardiac events. Methods: From 7 to 22 April 2021, expiratory CO levels were measured in a prospective registry including all consecutive patients admitted for acute cardiac event in 39 centres throughout France. The primary outcome was 1-year all-cause death. Initial in-hospital major adverse cardiac events (MAE; death, resuscitated cardiac arrest and cardiogenic shock) were also analysed. The study was registered at ClinicalTrials.gov (NCT05063097). Findings: Among 1379 patients (63 ± 15 years, 70% men), 368 (27%) were active smokers. Expiratory CO levels were significantly raised in active smokers compared to non-smokers. A CO level >11 parts per million (ppm) found in 94 (25.5%) smokers was associated with a significant increase in death (14.9% for CO > 11 ppm vs. 2.9% for CO ≤ 11 ppm; p < 0.001). Similar results were found after adjustment for comorbidities (hazard ratio [HR] [95% confidence interval (CI)]): 5.92 [2.43-14.38]) or parameters of in-hospital severity (HR 6.09, 95% CI [2.51-14.80]) and propensity score matching (HR 7.46, 95% CI [1.70-32.8]). CO > 11 ppm was associated with a significant increase in MAE in smokers during initial hospitalisation after adjustment for comorbidities (odds ratio [OR] 15.75, 95% CI [5.56-44.60]) or parameters of in-hospital severity (OR 10.67, 95% CI [4.06-28.04]). In the overall population, CO > 11 ppm but not smoking was associated with an increased rate of all-cause death (HR 4.03, 95% CI [2.33-6.98] and 1.66 [0.96-2.85] respectively). Interpretation: Elevated CO level is independently associated with a 6-fold increase in 1-year death and 10-fold in-hospital MAE in smokers hospitalized for acute cardiac events. Funding: Grant from Fondation Coeur & Recherche.

[Recreative drug use and cardiovascular disease]. / Consommation de drogues récréatives et pathologies cardiovasculaires.

Widely spread, and continuously increasing, recreational drug use in general population has been associated with cardiovascular events, as illustrated by clinical studies and supported by a pathophysiological rationale. Understanding the cardiovascular effects of drugs, screening, and secondary prevention are crucial components in the management of those patients in cardiology.

Impact of transfusion strategy on platelet aggregation and biomarkers in myocardial infarction patients with anemia.

BACKGROUND: Higher rates of thrombotic events have been reported in myocardial infarction (MI) patients requiring blood transfusion. The impact of blood transfusion strategy on thrombosis and inflammation is still unknown. OBJECTIVE: To compare the impact of a liberal vs. a restrictive transfusion strategy on P2Y12 platelet reactivity and biomarkers in the multicentric randomized REALITY trial. METHODS: Patients randomized to a liberal (hemoglobin ≤10 g/dL) or a restrictive (hemoglobin ≤8 g/dL) transfusion strategy had VASP-PRI platelet reactivity measured centrally in a blinded fashion and platelet reactivity unit (PRU) measured locally using encrypted VerifyNow; at baseline and after randomization. Biomarkers of thrombosis (P-selectin, PAI-1, vWF) and inflammation (TNF-α) were also measured. The primary endpoint was the change in the VASP-PRI (difference from baseline and post randomization) between the randomized groups. RESULTS: A total of 100 patients randomized were included in this study (n = 50 in each group). Transfused patients received on average 2.4 ± 1.6 units of blood. We found no differences in change of the VASP PRI (difference 1.2% 95% CI (-10.3-12.7%)) or by the PRU (difference 13.0 95% CI (-21.8-47.8)) before and after randomization in both randomized groups. Similar results were found in transfused patients (n = 71) regardless of the randomized group, VASP PRI (difference 1.7%; 95% CI (-9.5-1.7%)) or PRU (difference 27.0; 95% CI (-45.0-0.0)). We did not find an impact of transfusion strategy or transfusion itself in the levels of P-selectin, PAI-1, vWF, and TNF-α. CONCLUSION: In this study, we found no impact of a liberal vs. a restrictive transfusion strategy on platelet reactivity and biomarkers in MI patients with anemia. A conclusion that should be tempered due to missing patients with exploitable biological data that has affected our power to show a difference.

Rationale and design of the ARAMIS trial: Anakinra versus placebo, a double blind randomized controlled trial for the treatment of acute myocarditis.

BACKGROUND: Acute myocarditis is an inflammation of the myocardium that can cause life-threatening events. However, anti-inflammatory strategies did not reduce the risk of clinical outcomes in randomized trials. Recently, experimental studies have suggested that specific blockade of the interleukin-1ß immune innate pathway could be effective in acute myocarditis. AIM: To test the hypothesis that inhibition of the interleukin-1ß immune innate pathway can reduce the risk of clinical events in acute myocarditis. METHODS: The "Anakinra versus placebo double blind Randomized controlled trial for the treatment of Acute MyocarditIS" (ARAMIS) trial (ClinicalTrials.gov identifier: NCT03018834) is a national multicentre randomized parallel-group double blind study among symptomatic patients with elevated cardiac troponin and cardiac magnetic resonance-proven acute myocarditis. Patients (n=120) are randomized within 72hours of hospital admission to receive a daily subcutaneous dose of anakinra 100mg or placebo during the hospitalization, in addition to standard of care, including an angiotensin-converting enzyme inhibitor and a beta-blocker. The primary endpoint is the number of days alive free from any myocarditis complication, including ventricular arrhythmias, heart failure, recurrent chest pain requiring medication and ventricular dysfunction (defined as left ventricular ejection fraction<50%), from randomization to 28 days after hospital discharge. At 28 days after discharge, patients with normal left ventricular ejection fraction are then randomized to angiotensin-converting enzyme inhibitor continuation or discontinuation and all patients are followed for 1 year, with regular left ventricular function evaluation. CONCLUSIONS: ARAMIS is the first trial evaluating inhibition of the interleukin-1ß immune innate pathway in the setting of acute myocarditis. Although of small size, it will be the largest randomized trial in acute myocarditis, a serious and poorly studied cardiac condition.

Prevalence and impact of recreational drug use in patients with acute cardiovascular events.

OBJECTIVE: While recreational drug use is a risk factor for cardiovascular events, its exact prevalence and prognostic impact in patients admitted for these events are not established. We aimed to assess the prevalence of recreational drug use and its association with in-hospital major adverse events (MAEs) in patients admitted to intensive cardiac care units (ICCU). METHODS: In the Addiction in Intensive Cardiac Care Units (ADDICT-ICCU) study, systematic screening for recreational drugs was performed by prospective urinary testing all patients admitted to ICCU in 39 French centres from 7 to 22 April 2021. The primary outcome was prevalence of recreational drug detection. In-hospital MAEs were defined by death, resuscitated cardiac arrest, or haemodynamic shock. RESULTS: Of 1499 consecutive patients (63±15 years, 70% male), 161 (11%) had a positive test for recreational drugs (cannabis 9.1%, opioids 2.1%, cocaine 1.7%, amphetamines 0.7%, 3,4-methylenedioxymethamphetamine (MDMA) 0.6%). Only 57% of these patients declared recreational drug use. Patients who used recreational drugs exhibited a higher MAE rate than others (13% vs 3%, respectively, p<0.001). Recreational drugs were associated with a higher rate of in-hospital MAEs after adjustment for comorbidities (OR 8.84, 95% CI 4.68 to 16.7, p<0.001). After adjustment, cannabis, cocaine, and MDMA, assessed separately, were independently associated with in-hospital MAEs. Multiple drug detection was frequent (28% of positive patients) and associated with an even higher incidence of MAEs (OR 12.7, 95% CI 4.80 to 35.6, p<0.001). CONCLUSION: The prevalence of recreational drug use in patients hospitalised in ICCU was 11%. Recreational drug detection was independently associated with worse in-hospital outcomes. CLINICAL TRIAL REGISTRATION: NCT05063097.

Safety and incremental prognostic value of stress cardiovascular magnetic resonance in patients with known chronic kidney disease.

BACKGROUND: Cardiovascular disease (CVD) is the main cause of mortality in patients with chronic kidney disease (CKD). Although several studies have demonstrated the consistently high prognostic value of stress cardiovascular magnetic resonance (CMR), its prognostic value in patients with CKD is not well established. We aimed to assess the safety and the incremental prognostic value of vasodilator stress perfusion CMR in consecutive symptomatic patients with known CKD. METHODS: Between 2008 and 2021, we conducted a retrospective dual center study with all consecutive symptomatic patients with known stage 3 CKD, defined by estimated glomerular filtration rate (eGFR) between 30 and 60 ml/min/1.73 m2, referred for vasodilator stress CMR. All patients with eGFR < 30 ml/min/1.73 m2 (n = 62) were excluded due the risk of nephrogenic systemic fibrosis. All patients were followed for the occurrence of major adverse cardiovascular events (MACE) defined as cardiac death or recurrent nonfatal myocardial infarction (MI). Cox regression analysis was used to determine the prognostic value of stress CMR parameters. RESULTS: Of 825 patients with known CKD (71.4 ± 8.8 years, 70% men), 769 (93%) completed the CMR protocol. Follow-up was available in 702 (91%) (median follow-up 6.4 (4.0-8.2) years). Stress CMR was well tolerated without occurrence of death or severe adverse event related to the injection of gadolinium or cases of nephrogenic systemic fibrosis. The presence of inducible ischemia was associated with the occurrence of MACE (hazard ratio [HR] 12.50; 95% confidence interval [CI] 7.50-20.8; p < 0.001). In multivariable analysis, ischemia and late gadolinium enhancement were independent predictors of MACE (HR 15.5; 95% CI 7.72 to 30.9; and HR 4.67 [95% CI 2.83-7.68]; respectively, both p < 0.001). After adjustment, stress CMR findings showed the best improvement in model discrimination and reclassification above traditional risk factors (C-statistic improvement: 0.13; NRI = 0.477; IDI = 0.049). CONCLUSIONS: In patients with known stage 3 CKD, stress CMR is safe and its findings have an incremental prognostic value to predict MACE over traditional risk factors.

Left atrioventricular coupling index assessed using cardiac CT as a prognostic marker of cardiovascular death.

PURPOSE: The purpose of this study was to investigate the prognostic value of left atrioventricular coupling index (LACI) assessed by cardiac computed tomography (CT), to predict cardiovascular death in consecutive patients referred for cardiac CT with coronary analysis. MATERIALS AND METHODS: Between 2010 and 2020, we conducted a single-centre study with all consecutive patients without known cardiovascular disease referred for cardiac CT. LACI was defined as the ratio of left atrial to left ventricle end-diastolic volumes. The primary outcome was cardiovascular death. Cox regressions were used to evaluate the association between LACI and primary outcome after adjustment for traditional risk factors and cardiac CT angiography findings. RESULTS: In 1,444 patients (mean age, 70 ± 12 [standard deviation] years; 43% men), 67 (4.3%) patients experienced cardiovascular death after a median follow-up of 6.8 (Q1, Q3: 5.9, 9.1) years. After adjustment, LACI was positively associated with the occurrence of cardiovascular death (adjusted hazard ratio [HR], 1.07 [95% CI: 1.05-1.09] per 1% increment; P < 0.001), and all-cause death (adjusted HR, 1.05 [95% CI: 1.03-1.07] per 1% increment; P <0.001). After adjustment, a LACI ≥ 25% showed the best improvement in model discrimination and reclassification for predicting cardiovascular death above traditional risk factors and cardiac CT findings (C-statistic improvement: 0.27; Nnet reclassification improvement = 0.826; Integrative discrimination index =0.209, all P < 0.001; likelihood-ratio-test, P < 0.001). CONCLUSION: LACI measured by cardiac CT is independently associated with cardiovascular death and all-cause death in patients without known cardiovascular disease referred for cardiac CT, with an incremental prognostic value over traditional risk factors and cardiac CT findings.

Safety, feasibility, and prognostic value of stress perfusion CMR in patients with MR-conditional pacemaker.

AIMS: To assess the safety, feasibility, and prognostic value of stress cardiovascular magnetic resonance (CMR) in patients with pacemaker (PM). METHODS AND RESULTS: Between 2008 and 2021, we conducted a bi-centre longitudinal study with all consecutive patients with MR-conditional PM referred for vasodilator stress CMR at 1.5 T in the Institut Cardiovasculaire Paris Sud and Lariboisiere University Hospital. They were followed for the occurrence of major adverse cardiovascular events (MACE) defined as cardiac death or non-fatal myocardial infarction. Cox regression analyses were performed to determine the prognostic value of CMR parameters. The quality of CMR was rated by two observers blinded to clinical details. Of 304 patients who completed the CMR protocol, 273 patients (70% male, mean age 71 ± 9 years) completed the follow-up (median [interquartile range], 7.1 [5.4-7.5] years). Among those, 32 experienced a MACE (11.7%). Stress CMR was well tolerated with no significant change in lead thresholds or pacing parameters. Overall, the image quality was rated good or excellent in 84.9% of segments. Ischaemia and late gadolinium enhancement (LGE) were significantly associated with the occurrence of MACE (hazard ratio, HR: 11.71 [95% CI: 4.60-28.2]; and HR: 5.62 [95% CI: 2.02-16.21], both P < 0.001). After adjustment for traditional risk factors, ischaemia and LGE were independent predictors of MACE (HR: 5.08 [95% CI: 2.58-14.0]; and HR: 2.28 [95% CI: 2.05-3.76]; both P < 0.001). CONCLUSION: Stress CMR is safe, feasible and has a good discriminative prognostic value in consecutive patients with PM.

Immediate versus staged complete myocardial revascularization in patients with ST-segment elevation myocardial infarction and multivessel disease: A post hoc analysis of the randomized FLOWER-MI trial.

BACKGROUND: In patients with ST-segment elevation myocardial infarction and multivessel disease, percutaneous coronary intervention for non-culprit lesions is superior to treatment of the culprit lesion alone. The optimal timing for non-infarct-related artery revascularization - immediate versus staged - has not been investigated adequately. AIM: We aimed to assess clinical outcomes at 1 year in patients with ST-segment elevation myocardial infarction with multivessel disease using immediate versus staged non-infarct-related artery revascularization. METHODS: Outcomes were analysed in patients from the randomized FLOWER-MI trial, in whom, after successful primary percutaneous coronary intervention, non-culprit lesions were assessed using fractional flow reserve or angiography during the index procedure or during a staged procedure during the initial hospital stay, ≤5 days after the index procedure. The primary outcome was a composite of all-cause death, non-fatal myocardial infarction and unplanned hospitalization with urgent revascularization at 1year. RESULTS: Among 1171 patients enrolled in this study, 1119 (96.2%) had complete revascularization performed during a staged procedure, and 44 (3.8%) at the time of primary percutaneous coronary intervention. During follow-up, a primary outcome event occurred in one of the patients (2.3%) with an immediate strategy and in 55 patients (4.9%) with a staged strategy (adjusted hazard ratio 1.44, 95% confidence interval 0.39-12.69; P=0.64). CONCLUSIONS: Staged non-infarct-related artery complete revascularization was the strategy preferred by investigators in practice in patients with ST-segment elevation myocardial infarction with multivessel disease. This strategy was not superior to immediate revascularization, which, in the context of this trial, was used in a small proportion of patients. Further randomized studies are needed to confirm these observational findings.

Prevalence of psychoactive drug use in patients hospitalized for acute cardiac events: Rationale and design of the ADDICT-ICCU trial, from the Emergency and Acute Cardiovascular Care Working Group and the National College of Cardiologists in Training of the French Society of Cardiology.

BACKGROUND: Psychoactive drugs, including illicit drugs, are associated with an increased rate of cardiovascular events. The prevalence and outcome of patients using these drugs at the time of admission to an intensive cardiac care unit is unknown. AIM: To assess the prevalence of psychoactive drugs detected in consecutive patients hospitalized in an intensive cardiac care unit for an acute cardiovascular event. METHODS: This is a nationwide prospective multicentre study, involving 39 centres throughout France, including all consecutive patients hospitalized in an intensive cardiac care unit within 2weeks. Psychoactive drug use will be assessed systematically by urine drug assay within 2hours of intensive cardiac care unit admission, to detect illicit (cannabinoids, cocaine, amphetamines, ecstasy, heroin and other opioids) and non-illicit (barbiturates, benzodiazepines, tricyclic antidepressants, methadone and buprenorphine) psychoactive drugs. Smoking will be investigated systematically by exhaled carbon monoxide measurement, and alcohol consumption using a standardized questionnaire. In-hospital major adverse events, including death, resuscitated cardiac arrest and cardiogenic shock, will be recorded. After discharge, all-cause death and major adverse cardiovascular events will be recorded systematically and adjudicated at 12months of follow-up. RESULTS: The primary outcome will be the prevalence of psychoactive drugs detected by systematic screening among all patients hospitalized in an intensive cardiac care unit. The in-hospital major adverse events will be analysed according to the presence or absence of detected psychoactive drugs. Subgroup analysis stratified by initial clinical presentation and type of psychoactive drug will be performed. CONCLUSIONS: This is the first prospective multicentre study to assess the prevalence of psychoactive drugs detected by systematic screening in consecutive patients hospitalized for acute cardiovascular events.

Machine-Learning Score Using Stress CMR for Death Prediction in Patients With Suspected or Known CAD.

BACKGROUND: In patients with suspected or known coronary artery disease, traditional prognostic risk assessment is based on a limited selection of clinical and imaging findings. Machine learning (ML) methods can take into account a greater number and complexity of variables. OBJECTIVES: This study sought to investigate the feasibility and accuracy of ML using stress cardiac magnetic resonance (CMR) and clinical data to predict 10-year all-cause mortality in patients with suspected or known coronary artery disease, and compared its performance with existing clinical or CMR scores. METHODS: Between 2008 and 2018, a retrospective cohort study with a median follow-up of 6.0 (IQR: 5.0-8.0) years included all consecutive patients referred for stress CMR. Twenty-three clinical and 11 stress CMR parameters were evaluated. ML involved automated feature selection by random survival forest, model building with a multiple fractional polynomial algorithm, and 5 repetitions of 10-fold stratified cross-validation. The primary outcome was all-cause death based on the electronic National Death Registry. The external validation cohort of the ML score was performed in another center. RESULTS: Of 31,752 consecutive patients (mean age: 63.7 ± 12.1 years, and 65.7% male), 2,679 (8.4%) died with 206,453 patient-years of follow-up. The ML score (ranging from 0 to 10 points) exhibited a higher area under the curve compared with Clinical and Stress Cardiac Magnetic Resonance score, European Systematic Coronary Risk Estimation score, QRISK3 score, Framingham Risk Score, and stress CMR data alone for prediction of 10-year all-cause mortality (ML score: 0.76 vs Clinical and Stress Cardiac Magnetic Resonance score: 0.68, European Systematic Coronary Risk Estimation score: 0.66, QRISK3 score: 0.64, Framingham Risk Score: 0.63, extent of inducible ischemia: 0.66, extent of late gadolinium enhancement: 0.65; all P < 0.001). The ML score also exhibited a good area under the curve in the external cohort (0.75). CONCLUSIONS: The ML score including clinical and stress CMR data exhibited a higher prognostic value to predict 10-year death compared with all traditional clinical or CMR scores.

Coronary Computed Tomography Angiography Analysis of Calcium Content to Identify Non-culprit Vulnerable Plaques in Patients With Acute Coronary Syndrome.

Background: Aside from the culprit plaque, the presence of vulnerable plaques in patients with acute coronary syndrome (ACS) may be associated with future cardiac events. A link between calcification and plaque rupture has been previously described. Aim: To assess whether analysis of the calcium component of coronary plaques using CT angiography, coronary computed tomographic angiography (CCTA) can help to detect additional vulnerable plaques in patients with non-ST elevation myocardial infarction (NSTEMI). Materials And Methods: Cross sectional study of consecutive patients referred for NSTEMI from 30 July to 30 August 2018 with CCTA performed before coronary angiography with systematic optical coherence tomography (OCT) analysis of all coronary arteries within 24 h of clinical onset of NSTEMI. Three types of plaques were defined: culprit plaques defined by angiography (vulnerable culprit plaques-VCP) - plaques with a fibrous cap thickness < 65 microns or thrombus in OCT (vulnerable non-culprit plaque-VNCP) - plaques with a fibrous cap thickness ≥ 65 microns in OCT (stable plaque-SP). Results: A total of 134 calcified plaques were identified in 29 patients (73% male, 59 ± 14 years) with 29(22%) VCP, 28(21%) VNCP and 77(57%) SP. Using CCTA analysis of the calcium component, factors associated with vulnerable plaques were longer calcification length, larger calcification volume, lower calcium mass, higher Agatston score plaque-specific (ASp), presence of spotty calcifications and an intimal position in the wall. In multivariate analysis, ASp, calcification length and spotty calcifications were independently associated to vulnerable plaques. There was no difference between VCP and VNCP. Conclusions: CCTA analysis of calcium component of the plaque could help to identify additional vulnerable plaques in NSTEMI patients.