New-onset atrial fibrillation and chronic coronary syndrome in the CLARIFY registry.

BACKGROUND AND AIMS: Data on new-onset atrial fibrillation (NOAF) in patients with chronic coronary syndromes (CCS) are scarce. This study aims to describe the incidence, predictors, and impact on cardiovascular (CV) outcomes of NOAF in CCS patients. METHODS: Data from the international (45 countries) CLARIFY registry (prospeCtive observational LongitudinAl RegIstry oF patients with stable coronary arterY disease) were used. Among 29 001 CCS outpatients without previously reported AF at baseline, patients with at least one episode of AF/flutter diagnosed during 5-year follow-up were compared with patients in sinus rhythm throughout the study. RESULTS: The incidence rate of NOAF was 1.12 [95% confidence interval (CI) 1.06-1.18] per 100 patient-years (cumulative incidence at 5 years: 5.0%). Independent predictors of NOAF were increasing age, increasing body mass index, low estimated glomerular filtration rate, Caucasian ethnicity, alcohol intake, and low left ventricular ejection fraction, while high triglycerides were associated with lower incidence. New-onset atrial fibrillation was associated with a substantial increase in the risk of adverse outcomes, with adjusted hazard ratios of 2.01 (95% CI 1.61-2.52) for the composite of CV death, non-fatal myocardial infarction, or non-fatal stroke, 2.61 (95% CI 2.04-3.34) for CV death, 1.64 (95% CI 1.07-2.50) for non-fatal myocardial infarction, 2.27 (95% CI 1.85-2.78) for all-cause death, 8.44 (95% CI 7.05-10.10) for hospitalization for heart failure, and 4.46 (95% CI 2.85-6.99) for major bleeding. CONCLUSIONS: Among CCS patients, NOAF is common and is strongly associated with worse outcomes. Whether more intensive preventive measures and more systematic screening for AF would improve prognosis in this population deserves further investigation.

Pharmacological coronary spasm provocative testing in clinical practice: A French Coronary Atheroma and Interventional Cardiology Group (GACI) position paper.

Vasospastic angina, also described as Prinzmetal angina, was first described as a variant form of angina at rest with transient ST-segment elevation; it is common and present in many clinical scenarios, including chronic and acute coronary syndromes, sudden cardiac death, arrhythmia and syncope. However, vasospastic angina remains underdiagnosed, and provocative tests are rarely performed. The gold-standard diagnostic approach uses invasive coronary angiography to induce coronary spasm using ergonovine, methylergonovine or acetylcholine as provocative stimuli. The lack of uniform protocol decreases the use and performance of these tests, accounting for vasospastic angina underestimation. This position paper from the French Coronary Atheroma and Interventional Cardiology Group (GACI) aims to review the indications for provocative tests, the testing conditions, drug protocols and positivity criteria.

Comparison of different percutaneous revascularisation timing strategies in patients undergoing transcatheter aortic valve implantation.

BACKGROUND: The optimal timing to perform percutaneous coronary interventions (PCI) in transcatheter aortic valve implantation (TAVI) patients remains unknown. AIMS: We sought to compare different PCI timing strategies in TAVI patients. METHODS: The REVASC-TAVI registry is an international registry including patients undergoing TAVI with significant, stable coronary artery disease (CAD) at preprocedural workup. In this analysis, patients scheduled to undergo PCI before, after or concomitantly with TAVI were included. The main endpoints were all-cause death and a composite of all-cause death, stroke, myocardial infarction (MI) or rehospitalisation for congestive heart failure (CHF) at 2 years. Outcomes were adjusted using the inverse probability treatment weighting (IPTW) method. RESULTS: A total of 1,603 patients were included. PCI was performed before, after or concomitantly with TAVI in 65.6% (n=1,052), 9.8% (n=157) or 24.6% (n=394), respectively. At 2 years, all-cause death was significantly lower in patients undergoing PCI after TAVI as compared with PCI before or concomitantly with TAVI (6.8% vs 20.1% vs 20.6%; p<0.001). Likewise, the composite endpoint was significantly lower in patients undergoing PCI after TAVI as compared with PCI before or concomitantly with TAVI (17.4% vs 30.4% vs 30.0%; p=0.003). Results were confirmed at landmark analyses considering events from 0 to 30 days and from 31 to 720 days. CONCLUSIONS: In patients with severe aortic stenosis and stable coronary artery disease scheduled for TAVI, performance of PCI after TAVI seems to be associated with improved 2-year clinical outcomes compared with other revascularisation timing strategies. These results need to be confirmed in randomised clinical trials.

Complementary evidence on the performance of coronary stents generated by a randomized controlled trial and a worldwide registry.

BACKGROUND: Large-scale registries can provide valuable complementary data to randomized controlled trials (RCT) for the postmarketing evaluation of coronary stents, but their scientific relevance remains debated. METHODS: We sought to compare the evidence on the performance of a single coronary stent platform generated by the RCT for its regulatory approval and a well-conducted international registry. Patients treated with the Ultimaster coronary stent in the CENTURY II (CII-UM) trial (n = 551) were compared to patients in the real-world e-ULTIMASTER (e-UM) registry (n = 35,389). All major events were adjudicated by an independent clinical event committee in both studies. Propensity weighted analysis was used to balance baseline and procedural differences between the 2 populations. RESULTS: Coronary artery disease was more complex in e-UM compared to CII-UM, including more acute coronary syndromes, multivessel disease, left main, arterial, or venous grafts, and chronic total occlusions (P < .005 for all). At one-year follow-up and after excluding periprocedural myocardial infarction (MI) there was no statistically significant difference between CII-UM and e-UM regarding all-cause death (hazard ratio [HR] 0.55, 95% confidence interval [CI] 0.26-1.20, P = .14), cardiac death (HR 0.71, 95% CI 0.29-1.72, P = .45), target lesion failure (HR 1.18, 95% CI 0.78-1.78, P = .44), and target vessel MI (HR 0.76, 95% CI 0.24-2.38, P = .63). However, target vessel revascularization rate was significantly higher in CII-UM than in e-UM, HR 1.78, 95% CI 1.23-2.56, P = .002. CONCLUSIONS: A well-conducted large-scale registry can provide valuable complementary evidence to RCTs on the postmarket performance of new coronary stents, across a wider range of uses and various geographic areas.

Management of Myocardial Revascularization in Patients With Stable Coronary Artery Disease Undergoing Transcatheter Aortic Valve Implantation.

BACKGROUND: The best management of stable coronary artery disease (CAD) in patients undergoing transcatheter aortic valve implantation (TAVI) is still unclear due to the marked inconsistency of the available evidence. METHODS: The REVASC-TAVI registry (Management of Myocardial Revascularization in Patients Undergoing Transcatheter Aortic Valve Implantation With Coronary Artery Disease) collected data from 30 centers worldwide on patients undergoing TAVI who had significant, stable CAD at preprocedural work-up. For the purposes of this analysis, patients with either complete or incomplete myocardial revascularization were compared in a propensity score matched analysis, to take into account of baseline confounders. The primary and co-primary outcomes were all-cause death and the composite of all-cause death, stroke, myocardial infarction, and rehospitalization for heart failure, respectively, at 2 years. RESULTS: Among 2407 patients enrolled, 675 pairs of patients achieving complete or incomplete myocardial revascularization were matched. The primary (21.6% versus 18.2%, hazard ratio' 0.88 [95% CI, 0.66-1.18]; P=0.38) and co-primary composite (29.0% versus 27.1%, hazard ratio' 0.97 [95% CI, 0.76-1.24]; P=0.83) outcome did not differ between patients achieving complete or incomplete myocardial revascularization, respectively. These results were consistent across different prespecified subgroups of patients (< or >75 years of age, Society of Thoracic Surgeons score > or <4%, angina at baseline, diabetes, left ventricular ejection fraction > or <40%, New York Heart Association class I/II or III/IV, renal failure, proximal CAD, multivessel CAD, and left main/proximal anterior descending artery CAD; all P values for interaction >0.10). CONCLUSIONS: The present analysis of the REVASC-TAVI registry showed that, among TAVI patients with significant stable CAD found during the TAVI work-up, completeness of myocardial revascularization achieved either staged or concomitantly with TAVI was similar to a strategy of incomplete revascularization in reducing the risk of all cause death, as well as the risk of death, stroke, myocardial infarction, and rehospitalization for heart failure at 2 years, regardless of the clinical and anatomical situations.

Machine learning-based scoring system to predict in-hospital outcomes in patients hospitalized with COVID-19.

BACKGROUND: The evolution of patients hospitalized with coronavirus disease 2019 (COVID-19) is still hard to predict, even after several months of dealing with the pandemic. AIMS: To develop and validate a score to predict outcomes in patients hospitalized with COVID-19. METHODS: All consecutive adults hospitalized for COVID-19 from February to April 2020 were included in a nationwide observational study. Primary composite outcome was transfer to an intensive care unit from an emergency department or conventional ward, or in-hospital death. A score that estimates the risk of experiencing the primary outcome was constructed from a derivation cohort using stacked LASSO (Least Absolute Shrinkage and Selection Operator), and was tested in a validation cohort. RESULTS: Among 2873 patients analysed (57.9% men; 66.6±17.0 years), the primary outcome occurred in 838 (29.2%) patients: 551 (19.2%) were transferred to an intensive care unit; and 287 (10.0%) died in-hospital without transfer to an intensive care unit. Using stacked LASSO, we identified 11 variables independently associated with the primary outcome in multivariable analysis in the derivation cohort (n=2313), including demographics (sex), triage vitals (body temperature, dyspnoea, respiratory rate, fraction of inspired oxygen, blood oxygen saturation) and biological variables (pH, platelets, C-reactive protein, aspartate aminotransferase, estimated glomerular filtration rate). The Critical COVID-19 France (CCF) risk score was then developed, and displayed accurate calibration and discrimination in the derivation cohort, with C-statistics of 0.78 (95% confidence interval 0.75-0.80). The CCF risk score performed significantly better (i.e. higher C-statistics) than the usual critical care risk scores. CONCLUSIONS: The CCF risk score was built using data collected routinely at hospital admission to predict outcomes in patients with COVID-19. This score holds promise to improve early triage of patients and allocation of healthcare resources.

Safety and efficacy of 48 mm Xience Xpedition everolimus-eluting stent for the treatment of long coronary lesions.

INTRODUCTION: Long drug-eluting stents may limit the issue of overlapping multiple stents when treating long coronary lesions. AIM: The aim of the study was to assess the safety and efficacy of the 48 mm Xience Xpedition everolimus-eluting stent (48mm-EES) for the treatment of long coronary lesions, in an all-comer population. METHODS: Patients receiving at least one 48mm-EES were prospectively included from March 2014 to December 2018. The primary endpoint was target lesion failure (TLF), defined as a composite of cardiac death, target vessel myocardial infarction, and clinically driven target lesion revascularization (TLR) at 1 year. The main secondary endpoint was the patient-oriented composite endpoint (POCE) defined as a composite of death, stroke, myocardial infarction, and reintervention. RESULTS: A total of 268 patients with 276 long coronary lesions, including 94 chronic total occlusions (CTO), were successfully treated using at least one 48mm-EES. The total stent length per lesion was 66 ± 22 mm. A single 48mm-EES was suitable to successfully treat the target lesion in 48% of cases (60% for non-CTO lesions). One-year follow-up rate was 96.3%. TLF occurred in 13 patients (5.3%), mainly driven by TLR (4.1%). Two cardiac death occurred (0.7%). POCE occurred in 30 patients (11.6%) mainly driven by repeat revascularization (9.7%). Definite stent thrombosis was observed in two patients (0.7%). No difference was observed in one-year outcomes between single 48mm-EES and multiple stents implantation as well as between CTO and non-CTO lesions. CONCLUSION: The 48mm-EES is safe and effective to treat long coronary lesions, including CTOs, and provides attractive cost-effectiveness by limiting multiple stenting.

Prognostic value of right ventricular dilatation in patients with COVID-19: a multicentre study.

AIMS: Although cardiac involvement has prognostic significance in coronavirus disease 2019 (COVID-19) and is associated with severe forms, few studies have explored the prognostic role of transthoracic echocardiography (TTE). We investigated the link between TTE parameters and prognosis in COVID-19. METHODS AND RESULTS: Consecutive patients with COVID-19 admitted to 24 French hospitals were retrospectively included. Comprehensive data, including clinical and biological parameters, were recorded at admission. Focused TTE was performed during hospitalization, according to clinical indication. Patients were followed for a primary composite outcome of death or transfer to intensive care unit (ICU) during hospitalization. Among 2878 patients, 445 (15%) underwent TTE. Most of these had cardiovascular risk factors, a history of cardiovascular disease, and were on cardiovascular treatments. Dilatation and dysfunction were observed in, respectively, 12% (48/412) and 23% (102/442) of patients for the left ventricle, and in 12% (47/407) and 16% (65/402) for the right ventricle (RV). Primary composite outcome occurred in 44% (n = 196) of patients [9% (n = 42) for death without ICU transfer and 35% (n = 154) for admission to ICU]. RV dilatation was the only TTE parameter associated with the primary outcome. After adjustment, male sex [hazard ratio (HR) 1.56, 95% confidence interval (CI) 1.09 - 2.25; P = 0.02], higher body mass index (HR 1.10, 95% CI 1.02 - 1.18; P = 0.01), anticoagulation (HR 0.53, 95% CI 0.33 - 0.86; P = 0.01), and RV dilatation (HR 1.66, 95% CI 1.05 - 2.64; P = 0.03) remained independently associated with the primary outcome. CONCLUSION: Echocardiographic evaluation of RV dilatation could be useful for assessing risk of severe COVID-19 developing in hospitalized patients.

Cardiovascular Characteristics and Outcomes of Young Patients with COVID-19.

Although 18-45-year-old (y-o) patients represent a significant proportion of patients hospitalized for COVID-19, data concerning the young population remain scarce. The Critical COVID France (CCF) study was an observational study including consecutive patients hospitalized for COVID-19 in 24 centers between 26 February and 20 April 2020. The primary composite outcome included transfer to the intensive care unit (ICU) or in-hospital death. Secondary outcomes were cardiovascular (CV) complications. Among 2868 patients, 321 (11.2%) patients were in the 18-45-y-o range. In comparison with older patients, young patients were more likely to have class 2 obesity and less likely to have hypertension, diabetes and dyslipidemia. The primary outcome occurred less frequently in 18-45-y-o patients in comparison with patients > 45 years old (y/o) (16.8% vs. 30.7%, p < 0.001). The 18-45-y-o patients presented with pericarditis (2.2% vs. 0.5%, p = 0.003) and myocarditis (2.5% vs. 0.6%, p = 0.002) more frequently than patients >45 y/o. Acute heart failure occurred less frequently in 18-45-y-o patients (0.9% vs. 7.2%, p < 0.001), while thrombotic complications were similar in young and older patients. Whereas both transfer to the ICU and in-hospital death occurred less frequently in young patients, COVID-19 seemed to have a particular CV impact in this population.

Characteristics and outcomes of patients hospitalized for COVID-19 in France: The Critical COVID-19 France (CCF) study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to a public health crisis. Only limited data are available on the characteristics and outcomes of patients hospitalized for COVID-19 in France. AIMS: To investigate the characteristics, cardiovascular complications and outcomes of patients hospitalized for COVID-19 in France. METHODS: The Critical COVID-19 France (CCF) study is a French nationwide study including all consecutive adults with a diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection hospitalized in 24 centres between 26 February and 20 April 2020. Patients admitted directly to intensive care were excluded. Clinical, biological and imaging parameters were systematically collected at hospital admission. The primary outcome was in-hospital death. RESULTS: Of 2878 patients included (mean±SD age 66.6±17.0 years, 57.8% men), 360 (12.5%) died in the hospital setting, of which 7 (20.7%) were transferred to intensive care before death. The majority of patients had at least one (72.6%) or two (41.6%) cardiovascular risk factors, mostly hypertension (50.8%), obesity (30.3%), dyslipidaemia (28.0%) and diabetes (23.7%). In multivariable analysis, older age (hazard ratio [HR] 1.05, 95% confidence interval [CI] 1.03-1.06; P<0.001), male sex (HR 1.69, 95% CI 1.11-2.57; P=0.01), diabetes (HR 1.72, 95% CI 1.12-2.63; P=0.01), chronic kidney failure (HR 1.57, 95% CI 1.02-2.41; P=0.04), elevated troponin (HR 1.66, 95% CI 1.11-2.49; P=0.01), elevated B-type natriuretic peptide or N-terminal pro-B-type natriuretic peptide (HR 1.69, 95% CI 1.0004-2.86; P=0.049) and quick Sequential Organ Failure Assessment score ≥2 (HR 1.71, 95% CI 1.12-2.60; P=0.01) were independently associated with in-hospital death. CONCLUSIONS: In this large nationwide cohort of patients hospitalized for COVID-19 in France, cardiovascular comorbidities and risk factors were associated with a substantial morbi-mortality burden.

Characteristics and impact of cardiovascular comorbidities on coronavirus disease 2019 in women: A multicentre cohort study.

BACKGROUND: Although women account for up to half of patients hospitalized for coronavirus disease 2019 (COVID-19), no specific data have been reported in this population. AIMS: To assess the burden and impact of cardiovascular comorbidities in women with COVID-19. METHODS: All consecutive patients hospitalized for COVID-19 across 24 hospitals from 26 February to 20 April 2020 were included. The primary composite outcome was transfer to an intensive care unit or in-hospital death. RESULTS: Among 2878 patients, 1212 (42.1%) were women. Women were older (68.3±18.0 vs. 65.4±16.0 years; P<0.001), but had less prevalent cardiovascular comorbidities than men. Among women, 276 (22.8%) experienced the primary outcome, including 161 (13.3%) transfers to an intensive care unit and 115 (9.5%) deaths without transfer to intensive care unit. The rate of in-hospital death or transfer to an intensive care unit was lower in women versus men (crude hazard ratio [HR]: 0.62, 95% confidence interval [CI]: 0.53-0.72). Age (adjusted HR: 1.05 per 5-year increase, 95% CI: 1.01-1.10), body mass index (adjusted HR: 1.06 per 2-unit increase, 95% CI: 1.02-1.10), chronic kidney disease (adjusted HR: 1.57, 95% CI: 1.11-2.22) and heart failure (adjusted HR: 1.52, 95% CI: 1.04-2.22) were independently associated with the primary outcome in women. Elevated B-type natriuretic peptide/N-terminal prohormone of B-type natriuretic peptide (adjusted HR: 2.41, 95% CI: 1.70-3.44) and troponin (adjusted HR: 2.00, 95% CI: 1.39-2.88) concentrations at admission were also associated with the primary outcome, even in women free of previous coronary artery disease or heart failure. CONCLUSIONS: Although female sex was associated with a lower risk of transfer to an intensive care unit or in-hospital death, COVID-19 remained associated with considerable morbimortality in women, especially in those with cardiovascular diseases.

Association of diabetes and outcomes in patients with COVID-19: Propensity score-matched analyses from a French retrospective cohort.

BACKGROUND: Our study aimed to compare the clinical outcomes of patients with and without diabetes admitted to hospital with COVID-19. METHODS: This retrospective multicentre cohort study comprised 24 tertiary medical centres in France, and included 2851 patients (675 with diabetes) hospitalized for COVID-19 between 26 February and 20 April 2020. A propensity score-matching (PSM) method (1:1 matching including patients' characteristics, medical history, vital statistics and laboratory results) was used to compare patients with and without diabetes (n = 603 per group). The primary outcome was admission to an intensive care unit (ICU) and/or in-hospital death. RESULTS: After PSM, all baseline characteristics were well balanced between those with and without diabetes: mean age was 71.2 years; 61.8% were male; and mean BMI was 29 kg/m2. A history of cardiovascular, chronic kidney and chronic obstructive pulmonary diseases were found in 32.8%, 22.1% and 6.4% of participants, respectively. The risk of experiencing the primary outcome was similar in patients with or without diabetes [hazard ratio (HR): 1.16, 95% confidence interval (CI): 0.95-1.41; P = 0.14], and was 1.29 (95% CI: 0.97-1.69) for in-hospital death, 1.26 (95% CI: 0.9-1.72) for death with no transfer to an ICU and 1.14 (95% CI: 0.88-1.47) with transfer to an ICU. CONCLUSION: In this retrospective study cohort of patients hospitalized for COVID-19, diabetes was not significantly associated with a higher risk of severe outcomes after PSM. TRIAL REGISTRATION NUMBER: NCT04344327.

Outcomes of Transcatheter Aortic Valve Implantation in Patients Receiving Chronic Systemic Corticosteroid Treatment.

The aim of this study was to describe the effects of chronic systemic corticosteroid treatment (SCT) on early and late outcomes after transcatheter aortic valve implantation (TAVI). From October 2006 to November 2018, 1,299 patients underwent TAVI in our institution. Among them, 48 (3.7%) received chronic SCT at the time of procedure (SCT group). They were more frequently women (p = 0.08) and needed more often dialysis (p = 0.002). All other baseline characteristics were similar between both groups. At 30 days, there was no difference on mortality. However, after adjustment, the SCT group had more major vascular complications: 16.7% versus 7.4%, hazard ratio (HR) 2.52 (95% confidence interval [CI] 1.14 to 5.9, p = 0.023), major or life-threatening bleedings: 22.9% versus 12.4%, HR 2.02 (95% CI 1.00 to 4.08, p = 0.05), and tamponades: 8.3% versus 2.4%, HR 4.05 (95% CI 1.35 to 12.15, p <0.001) than the non-SCT group. One-year all-cause mortality was significantly higher in the SCT than in the non-SCT group (37.5% vs 12.5%, p <0.0001). Multivariate analysis confirmed that SCT use was an independent predictor of 1-year mortality (HR 2.29, 95% CI 1.16 to 4.50, p = 0.017). In conclusion, chronic use of SCT significantly increases the rates of early vascular complications, major or life-threatening bleedings and tamponade and is an independent predictor of 1-year all-cause mortality after TAVI.

Haemodynamic stress-induced breaches of the arterial intima trigger inflammation and drive atherogenesis.

AIMS: Inflammatory mediators, including blood cells and their products, contribute critically to atherogenesis, but the igniting triggers of inflammation remain elusive. Atherosclerosis develops at sites of flow perturbation, where the enhanced haemodynamic stress could initiate the atherogenic inflammatory process due to the occurrence of mechanic injury. We investigated the role of haemodynamic stress-induced breaches, allowing the entry of blood cells in the arterial intima, in triggering inflammation-driven atherogenesis. METHODS AND RESULTS: Human coronary samples isolated from explanted hearts, (n = 47) displayed signs of blood entry (detected by the presence of iron, ferritin, and glycophorin A) in the subintimal space (54%) as assessed by histology, immunofluorescence, high resolution episcopic microscopy, and scanning electron microscopy. Computational flow dynamic analysis showed that intimal haemorrhagic events occurred at sites of flow disturbance. Experimental carotid arteries from Apoe deficient mice showed discrete endothelial breaches and intimal haemorrhagic events specifically occurring at the site of flow perturbation, within 3 days after the exacerbation of the local haemodynamic stress. Endothelial tearing was associated with increased VCAM-1 expression and, within 7 days, substantial Ly6G+ leucocytes accumulated at the sites of erythrocyte-derived iron and lipids droplets accumulation, pathological intimal thickening and positive oil red O staining. The formation of fatty streaks at the sites of intimal breaches was prevented by the depletion of Ly6G+ leucocytes, suggesting that the local injury driven by haemodynamic stress-induced breaches triggers atherogenic inflammation. CONCLUSION: Haemodynamic-driven breaches of the arterial intima drive atherogenic inflammation by triggering the recruitment of leucocyte at sites of disturbed arterial flow.