European Association of Cardiovascular Imaging survey on cardiovascular multimodality imaging in acute myocarditis.

AIMS: To assess the current role of cardiac imaging in the diagnosis, management, and follow-up of patients with acute myocarditis (AM) through a European Association of Cardiovascular Imaging survey. METHODS AND RESULTS: A total of 412 volunteers from 74 countries responded to the survey. Most participants worked in tertiary centres (56%). All participants had access to echocardiography, while 79 and 75% had access to cardiac computed tomography angiography (CCTA) and cardiac magnetic resonance (CMR), respectively. Less than half (47%) had access to myocardial biopsy, and only 5% used this test routinely. CMR was performed within 7 days of presentation in 73% of cases. Non-ischaemic late gadolinium enhancement (LGE, 88%) and high-signal intensity in T2-weighted images (74%) were the most used diagnostic criteria for AM. CCTA was preferred to coronary angiography by 47% of participants to exclude coronary artery disease. Systematic prescription of beta-blockers and angiotensin-converting enzyme inhibitors was reported by 38 and 32% of participants. Around a quarter of participants declared considering LGE burden as a reason to treat. Most participants (90%) reported performing a follow-up echocardiogram, while 63% scheduled a follow-up CMR. The main reason for treatment discontinuation was improvement of left ventricular ejection fraction (89%), followed by LGE regression (60%). In two-thirds of participants, the decision to resume high-intensity sport was influenced by residual LGE. CONCLUSION: This survey confirms the high utilization of cardiac imaging in AM but reveals major differences in how cardiac imaging is used and how the condition is managed between centres, underlining the need for recommendation statements in this topic.

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.

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.

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.

Association of soluble Flt-1 with heart failure and cardiac morphology: The MESA angiogenesis study.

BACKGROUND: Soluble Fms-like tyrosine kinase 1 (sFlt-1) may inhibit angiogenesis. Higher levels of sFlt-1 are associated with worse prognosis in prevalent heart failure patients. The aim of this study was to better understand the role of sFlt-1 in heart failure pathogenesis by characterizing relationships between sFlt-1, cardiac morphology, and the composite outcome of incident heart failure or cardiovascular (CV) death in in a multiethnic cohort free of CV disease at baseline. METHODS: sFlt-1 was measured in 1,381 participants in the Multi-Ethnic Study of Atherosclerosis Angiogenesis sub-study. Linear regression was used to estimate the association between sFlt-1 and cardiac morphology and Cox proportional hazard regression was used to estimate associations with incident heart failure or CV mortality. RESULTS: Over a median follow-up of 13.1 years, higher sFlt-1 levels were associated with incident heart failure or CV mortality independent from CV risk factors or NT-proBNP levels (HR 1.17, 95% CI 1.10-1.26, p < 0.001). Higher sFlt-1 levels were also associated with greater baseline left ventricular (LV) mass by cardiac MRI and increased loss of LV mass over the 10 years following the baseline exam (p-value 0.02 for each), but this association was no longer statistically significant after adjustment for baseline NT-proBNP (p = 0.11 and 0.10 respectively). CONCLUSIONS: Baseline sFlt-1 levels are associated with incident heart failure and cardiovascular mortality independent of traditional CV risk factors or NT-proBNP. An association was also found with cardiac mass but was no longer significant after adjustment for NT-proBNP.

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.

Diagnosis and Treatment of Iron Deficiency in Heart Failure: OFICSel study by the French Heart Failure Working Group.

AIMS: Iron deficiency (ID) occurs in about 50% of patients with heart failure (HF). The European Society of Cardiology (ESC) recommends ID diagnostic testing in newly diagnosed patients with HF and during follow-up, with intravenous iron supplementation (IS) only recommended in patients with HF with reduced ejection fraction (HFrEF). This study aimed to assess prevalence, clinical characteristics, and application of ESC guidelines for ID and IS in patients with HF in the real-life clinical setting. METHODS AND RESULTS: The French transversal multicentre OFICSel registry (300 cardiologists) conducted in 2017 included patients hospitalized for HF at least once in the previous 5 years. Diverse adult patients were eligible including inpatients and outpatients and those with acute and chronic HF. Data were collected from cardiologists and patients using study-specific surveys. Data included demographic and clinical data, as well as HF and ID management data. Overall, 2822 patients, mainly male (69.3%) with a median age of 69 years (interquartile range 58-78), were included. A total of 1075 patients (38.1%) were tested for ID, with 364 (33.9%) diagnosed. Of these, 168 (46.2%) received IS: 128 (76.2%) intravenous IS and 40 (23.8%) oral. Among the 201 patients with HFrEF diagnosed with ID, 99 (49.3%) received IS: 79 (79.8%) intravenous IS and 20 (20.2%) oral. CONCLUSIONS: In clinical practice, only one-third of patients with HF had a diagnostic test for ID. In patients with ID with HFrEF, only 39.3% received intravenous IS as recommended. Thus, in general, cardiologists should be encouraged to follow the ESC guidelines to ensure optimal treatment for patients with HF.

Imaging Interstitial Fibrosis, Left Ventricular Remodeling, and Function in Stage A and B Heart Failure.

Myocardial interstitial fibrosis is part of the advanced disease stage of most cardiovascular pathologies. It has been characterized histologically in various disease settings from hypertensive heart disease and diabetic cardiomyopathy to severe aortic stenosis. It is also involved in the process of aging. In cardiovascular medicine, myocardial interstitial fibrosis is associated with several adverse outcomes, especially heart failure (HF) and sudden cardiac death. Until recently, clinical measures of interstitial fibrosis could only be made by invasive myocardial biopsy. The availability of cardiac magnetic resonance (CMR) T1 mapping techniques allows for the indirect measurement of interstitial space characteristics and extracellular volume size, which is closely correlated with collagen content and interstitial infiltration by amyloid and other molecules. There has been significant improvement in the accuracy and reproducibility of T1 acquisition sequences in the last decade; however, the correct use of this technique requires a solid CMR expertise in daily imaging practice. CMR has become the gold standard to assess left ventricular (LV) remodeling and functional features associated with interstitial fibrosis. These features can be detected in the early stages of HF. The main objective of this paper is to review the relevant results of preclinical and clinical observational studies that demonstrate the prognostic impact of interstitial fibrosis assessed by T1 mapping, as well as adverse left ventricular remodeling, as determinants of HF. Therefore, this review focuses on the pathological mechanisms underlying LV remodeling and interstitial fibrosis, in addition to the technical considerations involved in the assessment of interstitial LV fibrosis by CMR. It provides a thorough review of clinical evidence that demonstrates the association of interstitial fibrosis and other-CMR derived LV phenotypes with Stages A and B HF.

Prognostic value of vasodilator stress perfusion CMR in patients with previous coronary artery bypass graft.

AIMS: The accuracy and prognostic value of stress perfusion cardiac magnetic resonance (CMR) are established in coronary artery disease (CAD) patients. Because myocardial contrast kinetics may be altered after coronary artery bypass graft (CABG), most studies excluded CABG patients. This study aimed to assess the prognostic value of vasodilator stress perfusion CMR in CABG patients. METHODS AND RESULTS: Consecutive CABG patients referred for stress CMR were retrospectively included and followed for the occurrence of major adverse cardiovascular events (MACE) including cardiovascular (CV) death or non-fatal myocardial infarction (MI). Cox regression analyses were performed to determine the prognostic association of inducible ischaemia and late gadolinium enhancement (LGE) by CMR. Of 866 consecutive CABG patients, 852 underwent the stress CMR protocol and 771 (89%) completed the follow-up [median (interquartile range) 4.2 (3.3-6.2) years]. There were 85 MACE (63 CV deaths and 22 non-fatal MI). Using Kaplan-Meier analysis, the presence of inducible ischaemia identified the occurrence of MACE [hazard ratio (HR) 3.52, 95% confidence interval (CI): 2.27-5.48; P < 0.001] and CV death (HR 2.55, 95% CI: 1.52-4.25; P < 0.001). In a multivariable stepwise Cox regression including clinical characteristics and CMR indexes, the presence of inducible ischaemia was an independent predictor of a higher incidence of MACE (HR 3.22, 95% CI: 2.06-5.02; P < 0.001) and CV death (HR 2.15, 95% CI: 1.28-3.62; P = 0.003), and the same was observed for LGE (both P = 0.02). CONCLUSION: Stress CMR has a good discriminative prognostic value in patients after CABG, with a higher incidence of MACE and CV death in patients with inducible ischaemia and/or LGE.

Effects of sacubitril/valsartan on neprilysin targets and the metabolism of natriuretic peptides in chronic heart failure: a mechanistic clinical study.

AIM: This study aimed at evaluating the effects of sacubitril/valsartan on neprilysin (NEP), and the metabolism of natriuretic peptides in heart failure (HF) and providing additional mechanistic information on the mode of action of the drug. METHODS AND RESULTS: We enrolled 73 chronic HF patients who were switched from angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to sacubitril/valsartan. In addition to clinical and echocardiographic assessment, plasma biomarkers were measured at baseline, day 30 and day 90 after initiation of treatment. Sacubitril/valsartan led to decrease in New York Heart Association class and improvement of echocardiographic parameters, as well as a dose-dependent decrease in soluble NEP (sNEP) activity, while sNEP concentration remained unchanged. Neprilysin inhibition translated into an increase in its substrates such as atrial natriuretic peptide (ANP), substance P, and glucagon-like peptide 1, the latter translating into a decrease in fructosamine. Cardiac troponin and soluble ST2 levels, biomarkers of HF severity unrelated to NEP metabolism also decreased. While there was a ∼4-fold increase in ANP, we observed no change in plasma brain natriuretic peptide (BNP) and plasma BNP activity, and a mild decrease in N-terminal proBNP (NT-proBNP) concentrations. Finally, we found a progressive increase in the relationship between BNP and NT-proBNP, which strongly correlated with an increase in T71 proBNP glycosylation (R2 = 0.94). CONCLUSION: Sacubitril/valsartan rapidly and strongly reduced sNEP activity, leading to an increase in levels of NEP substrates. These data suggest a pleiotropic favourable impact of sacubitril/valsartan on the metabolism of HF patients with ANP rather than BNP as major effectors amongst natriuretic peptides.