Systematic Aetiological Assessment of Myocarditis: A Prospective Cohort Study.

BACKGROUND: Myocarditis is commonly diagnosed in the intensive care cardiology unit (ICCU). No current recommendation nor guideline aids exist for aetiological assessments. METHODS: From September 2021 to October 2023, 84 patients with acute myocarditis underwent thorough and systematic serum and blood cell panel evaluations to determine the most common causes of myocarditis. RESULTS: Of the 84 patients (median age 34 years, range 22-41 years, 79% male), 16 presented with complicated myocarditis. The systematic aetiological assessment revealed that 36% of patients were positive for lupus anticoagulant, 12% for antinuclear antibodies, 8% for anti-heart antibodies, and 12% for anti-striated muscle antibodies. Viral serology did not yield any significant results. After the aetiological assessment, one patient was diagnosed with an autoimmune inflammatory disorder (Still's disease). T-cell subset analyses indicated that myocarditis severity tended to increase with the T-cell lymphopenia status. CONCLUSIONS: A comprehensive, systematic aetiological assessment was of limited value in terms of predicting the clinical or therapeutic outcomes in myocarditis patients presenting to the ICCU.

Social and clinical vulnerability in stroke and STEMI management during the COVID-19 pandemic: a registry-based study.

OBJECTIVE: This study aims to evaluate whether the first wave of the COVID-19 pandemic resulted in a deterioration in the quality of care for socially and/or clinically vulnerable stroke and ST-segment elevation myocardial infarction (STEMI) patients. DESIGN: Two cohorts of STEMI and stroke patients in the Aquitaine neurocardiovascular registry. SETTING: Six emergency medical services, 30 emergency units, 14 hospitalisation units and 11 catheterisation laboratories in the Aquitaine region in France. PARTICIPANTS: This study involved 9218 patients (6436 stroke and 2782 STEMI patients) in the neurocardiovascular registry from January 2019 to August 2020. PRIMARY OUTCOME MEASURES: Care management times in both cohorts: first medical contact-to-procedure time for the STEMI cohort and emergency unit admission-to-imaging time for the stroke cohort. Associations between social (deprivation index) and clinical (age >65 years, neurocardiovascular history) vulnerabilities and care management times were analysed using multivariate linear mixed models, with an interaction on the time period (pre-wave, per-wave and post-first COVID-19 wave). RESULTS: The first medical contact procedure time was longer for elderly (p<0.001) and 'very socially disadvantaged' (p=0.003) STEMI patients, with no interaction regarding the COVID-19 period (age, p=0.54; neurocardiovascular history, p=0.70; deprivation, p=0.64). We found no significant association between vulnerabilities and the admission imaging time for stroke patients, and no interaction with respect to the COVID-19 period (age, p=0.81; neurocardiovascular history, p=0.34; deprivation, p=0.95). CONCLUSIONS: This study revealed pre-existing inequalities in care management times for vulnerable STEMI and stroke patients; however, these inequalities were neither accentuated nor reduced during the first COVID-19 wave. Measures implemented during the crisis did not alter the structured emergency pathway for these patients. TRIAL REGISTRATION NUMBER: NCT04979208.

Effects of healthcare system transformations spurred by the COVID-19 pandemic on management of stroke and STEMI: a registry-based cohort study in France.

OBJECTIVE: To assess the impact of changes in use of care and implementation of hospital reorganisations spurred by the COVID-19 pandemic (first wave) on the acute management times of patients who had a stroke and ST-segment elevation myocardial infarction (STEMI). DESIGN: Two cohorts of patients who had an STEMI and stroke in the Aquitaine Cardio-Neuro-Vascular (CNV) registry. SETTING: 6 emergency medical services, 30 emergency units (EUs), 14 hospitalisation units and 11 cathlabs in the Aquitaine region. PARTICIPANTS: This study involved 9218 patients (6436 patients who had a stroke and 2782 patients who had an STEMI) in the CNV Registry from January 2019 to August 2020. METHOD: Hospital reorganisations, retrieved in a scoping review, were collected from heads of hospital departments. Other data were from the CNV Registry. Associations between reorganisations, use of care and care management times were analysed using multivariate linear regression mixed models. Interaction terms between use-of-care variables and period (pre-wave, per-wave and post-wave) were introduced. MAIN OUTCOME MEASURES: STEMI cohort, first medical contact-to-procedure time; stroke cohort, EU admission-to-imaging time. RESULTS: Per-wave period management times deteriorated for stroke but were maintained for STEMI. Per-wave changes in use of care did not affect STEMI management. No association was found between reorganisations and stroke management times. In the STEMI cohort, the implementation of systematic testing at admission was associated with a 41% increase in care management time (exp=1.409, 95% CI 1.075 to 1.848, p=0.013). Implementation of plan blanc, which concentrated resources in emergency activities, was associated with a 19% decrease in management time (exp=0.801, 95% CI 0.639 to 1.023, p=0.077). CONCLUSIONS: The pandemic did not markedly alter the functioning of the emergency network. Although stroke patient management deteriorated, the resilience of the STEMI pathway was linked to its stronger structuring. Transversal reorganisations, aiming at concentrating resources on emergency care, contributed to maintenance of the quality of care. TRIAL REGISTRATION NUMBER: NCT04979208.

Glycaemic Variability and Hyperglycaemia as Prognostic Markers of Major Cardiovascular Events in Diabetic Patients Hospitalised in Cardiology Intensive Care Unit for Acute Heart Failure.

(1) Background: Hyperglycaemia and hypoglycaemia are both emerging risk factors for cardiovascular disease. Nevertheless, the potential effect of glycaemic variability (GV) on mid-term major cardiovascular events (MACE) in diabetic patients presenting with acute heart failure (AHF) remains unclear. This study investigates the prognostic value of GV in diabetic patients presenting with acute heart failure (AHF). (2) Methods: this was an observational study including consecutive patients with diabetes and AHF between January 2015 and November 2016. GV was calculated using standard deviation of glycaemia values during initial hospitalisation in the intensive cardiac care unit. MACE, including recurrent AHF, new-onset myocardial infarction, ischaemic stroke and cardiac death, were recorded. The predictive effects of GV on patient outcomes were analysed with respect to baseline characteristics and cardiac status. (3) Results: In total, 392 patients with diabetes and AHF were enrolled. During follow-up (median (interquartile range) 29 (6−51) months), MACE occurred in 227 patients (57.9%). In total, 92 patients died of cardiac causes (23.5%), 107 were hospitalised for heart failure (27.3%), 19 had new-onset myocardial infarction (4.8%) and 9 (2.3%) had an ischaemic stroke. Multivariable logistic regression analysis showed that GV > 50 mg/dL (2.70 mmol/L), age > 75 years, reduced left ventricular ejection fraction (LVEF < 30%) and female gender were independent predictors of MACE: hazard ratios (HR) of 3.16 (2.25−4.43; p < 0.001), 1.54 (1.14−2.08; p = 0.005), 1.47 (1.06−2.07; p = 0.02) and 1.43 (1.05−1.94; p = 0.03), respectively. (4) Conclusions: among other well-known factors of HF, a GV cut-off value of >50 mg/dL was the strongest independent predictive factor for mid-term MACE in patients with diabetes and AHF.

Decrease of Pdzrn3 is required for heart maturation and protects against heart failure.

Heart failure is the final common stage of most cardiopathies. Cardiomyocytes (CM) connect with others via their extremities by intercalated disk protein complexes. This planar and directional organization of myocytes is crucial for mechanical coupling and anisotropic conduction of the electric signal in the heart. One of the hallmarks of heart failure is alterations in the contact sites between CM. Yet no factor on its own is known to coordinate CM polarized organization. We have previously shown that PDZRN3, an ubiquitine ligase E3 expressed in various tissues including the heart, mediates a branch of the Planar cell polarity (PCP) signaling involved in tissue patterning, instructing cell polarity and cell polar organization within a tissue. PDZRN3 is expressed in the embryonic mouse heart then its expression dropped significantly postnatally corresponding with heart maturation and CM polarized elongation. A moderate CM overexpression of Pdzrn3 (Pdzrn3 OE) during the first week of life, induced a severe eccentric hypertrophic phenotype with heart failure. In models of pressure-overload stress heart failure, CM-specific Pdzrn3 knockout showed complete protection against degradation of heart function. We reported that Pdzrn3 signaling induced PKC ζ expression, c-Jun nuclear translocation and a reduced nuclear ß catenin level, consistent markers of the planar non-canonical Wnt signaling in CM. We then show that subcellular localization (intercalated disk) of junction proteins as Cx43, ZO1 and Desmoglein 2 was altered in Pdzrn3 OE mice, which provides a molecular explanation for impaired CM polarization in these mice. Our results reveal a novel signaling pathway that controls a genetic program essential for heart maturation and maintenance of overall geometry, as well as the contractile function of CM, and implicates PDZRN3 as a potential therapeutic target for the prevention of human heart failure.

Fractional Flow Reserve to Guide Treatment of Patients With Multivessel Coronary Artery Disease.

BACKGROUND: There is limited evidence that fractional flow reserve (FFR) is effective in guiding therapeutic strategy in multivessel coronary artery disease (CAD) beyond prespecified percutaneous coronary intervention or coronary graft surgery candidates. OBJECTIVES: The FUTURE (FUnctional Testing Underlying coronary REvascularization) trial aimed to evaluate whether a treatment strategy based on FFR was superior to a traditional strategy without FFR in the treatment of multivessel CAD. METHODS: The FUTURE trial is a prospective, randomized, open-label superiority trial. Multivessel CAD candidates were randomly assigned (1:1) to treatment strategy based on FFR in all stenotic (≥50%) coronary arteries or to a traditional strategy without FFR. In the FFR group, revascularization (percutaneous coronary intervention or surgery) was indicated for FFR ≤0.80 lesions. The primary endpoint was a composite of major adverse cardiac or cerebrovascular events at 1 year. RESULTS: The trial was stopped prematurely by the data safety and monitoring board after a safety analysis and 927 patients were enrolled. At 1-year follow-up, by intention to treat, there were no significant differences in major adverse cardiac or cerebrovascular events rates between groups (14.6% in the FFR group vs 14.4% in the control group; hazard ratio: 0.97; 95% confidence interval: 0.69-1.36; P = 0.85). The difference in all-cause mortality was nonsignificant, 3.7% in the FFR group versus 1.5% in the control group (hazard ratio: 2.34; 95% confidence interval: 0.97-5.18; P = 0.06), and this was confirmed with a 24 months' extended follow-up. FFR significantly reduced the proportion of revascularized patients, with more patients referred to exclusively medical treatment (P = 0.02). CONCLUSIONS: In patients with multivessel CAD, we did not find evidence that an FFR-guided treatment strategy reduced the risk of ischemic cardiovascular events or death at 1-year follow-up. (Functional Testing Underlying Coronary Revascularisation; NCT01881555).

Bail-out therapy in ST-segment elevation myocardial infarction due to calcified lesion causing stent underexpansion: Intravascular lithotripsy is in the lead.

A 52-year-old male was referred for an acute anterior ST-segment elevation myocardial infarction (STEMI). Coronary angiography revealed an acute left anterior descending artery occlusion. The patient was treated with a drug-eluting stent (DES). Despite long and repeated high-pressure inflations (>20 atm) of non-compliant balloons, OPN NCⓇ high-pressure balloon (SIS Medical AG; Frauenfeld, Switzerland), rotational atherectomy, and cutting balloon, there was a severe hourglass stent underexpansion caused by coronary calcification. Thus, intravascular lithotripsy (IVL) (Shockwave Medical, Fremont, CA, USA) was attempted to re-dilate this calcified lesion. Underexpansion was successfully treated after delivering 70 shockwaves to the narrowest segment. IVL delivers localized pulsatile sonic pressure waves inducing circumferential calcium modification and multiple fractures. Our observation illustrates the additional value of coronary lithotripsy as a bail-out procedure to tackle severely calcified, de novo coronary lesions causing stent underexpansion in the context of STEMI, when all other available techniques failed. .

ST-segment elevation myocardial infarction: Management and association with prognosis during the COVID-19 pandemic in France.

BACKGROUND: Systems of care have been challenged to control progression of the COVID-19 pandemic. Whether this has been associated with delayed reperfusion and worse outcomes in French patients with ST-segment elevation myocardial infarction (STEMI) is unknown. AIM: To compare the rate of STEMI admissions, treatment delays, and outcomes between the first peak of the COVID-19 pandemic in France and the equivalent period in 2019. METHODS: In this nationwide French survey, data from consecutive STEMI patients from 65 centres referred for urgent revascularization between 1 March and 31 May 2020, and between 1 March and 31 May 2019, were analysed. The primary outcome was a composite of in-hospital death or non-fatal mechanical complications of acute myocardial infarction. RESULTS: A total of 6306 patients were included. During the pandemic peak, a 13.9±6.6% (P=0.003) decrease in STEMI admissions per week was observed. Delays between symptom onset and percutaneous coronary intervention were longer in 2020 versus 2019 (270 [interquartile range 150-705] vs 245 [140-646]min; P=0.013), driven by the increase in time from symptom onset to first medical contact (121 [60-360] vs 150 [62-420]min; P=0.002). During 2020, a greater number of mechanical complications was observed (0.9% vs 1.7%; P=0.029) leading to a significant difference in the primary outcome (112 patients [5.6%] in 2019 vs 129 [7.6%] in 2020; P=0.018). No significant difference was observed in rates of orotracheal intubation, in-hospital cardiac arrest, ventricular arrhythmias and cardiogenic shock. CONCLUSIONS: During the first peak of the COVID-19 pandemic in France, there was a decrease in STEMI admissions, associated with longer ischaemic time, exclusively driven by an increase in patient-related delays and an increase in mechanical complications. These findings suggest the need to encourage the population to seek medical help in case of symptoms.

A case of anomalous aortic origin of coronary artery associated with a coved-type electrocardiogram.

Brugada syndrome (BrS) is a sudden cardiac death syndrome characterized by a coved-type electrocardiogram (ECG). Different disorders, such as ischemia, can emulate a Brugada-pattern ECG (Brugada phenocopy). We report herein, the first case of surgical epicardial electrophysiological mapping in a successfully resuscitated patient with an anomalous aortic origin of the coronary artery (AAOCA) associated with a coved-type ECG. It was debatable whether the coved-type ECG and the abnormal arrhythmogenic substrate in the epicardial right ventricular outflow tract were derived from BrS or from repetitive ischemia due to AAOCA; however, the epicardial electrophysiological mapping helped in deciding the treatment strategy.

OCT and CMR for the Diagnosis of Patients Presenting With MINOCA and Suspected Epicardial Causes.

OBJECTIVES: Among all patients presenting with myocardial infarction with nonobstructive coronary arteries (MINOCA), epicardial causes may be suspected when there is a correlation between electrocardiogram (ECG) changes and regional wall motion abnormalities (WMAs). We evaluated the diagnostic yield of intravascular optical coherence tomography (OCT) and cardiac magnetic resonance (CMR) in this specific setting. BACKGROUND: OCT is able to identify different morphologic features of coronary plaques that are well known causes of MINOCA. Furthermore, CMR has become the gold standard for detection of myocardial infarction in the setting of MINOCA. METHODS: In a prospective 2-center study, consecutive patients with MINOCA including ECG features of ischemia associated with corresponding WMAs underwent OCT and CMR. RESULTS: Forty patients (mean age: 50 ± 11 years, 62.5% male, 32.5% with ST-segment elevation) were enrolled. Coronary arteries were normal on coronary angiography in 10 patients (25%); 18 patients (45%) presented minimal lumen irregularities, whereas the remaining 12 patients (30%) showed mild to moderate (≥30% but <50%) coronary lesions. Plaque rupture, eruptive calcific nodule, plaque erosion, lone thrombus, and spontaneous coronary artery dissection were found in 14 (35%), 1 (2.5%), 12 (30%), 3 (7.5%), and 2 (5%) patients, respectively. Acute myocardial infarction was evident at CMR in 31 of 40 patients (77.5%). Twenty-three patients (57.5%) had a substrate and/or diagnosis supported by both techniques with an evident relationship between the findings obtained by the 2 techniques. By coupling OCT with CMR, a substrate and/or diagnosis was found in 100% of cases. CONCLUSIONS: OCT coupled with CMR can provide a clear substrate and/or diagnosis in the vast majority of patients presenting with MINOCA including ECG features of ischemia associated with corresponding WMAs.