Mechanical complications in ST-elevation myocardial infarction: The impact of pre-hospital delay

International audienceAims: Mechanical complications (MC) (i.e., free wall rupture (FWR), papillary muscle rupture (PMR) and ventricular septal rupture (VSR)) are rare complications of ST- elevation acute myocardial infarction (STEMI). Incidence of MC according to pre-hospital delay remains unknown. We aimed to determine the rates of MC according to pre-hospital delay.Methods: Analysis was conducted on the MODIF registry data. Patients were allocated to four groups according to pre-hospital delay: 0 to 12 h, 12 to 24 h, 24 to 36 h and 36 to 48 h.Results: 6185 patients with complete data were analyzed. Mean age was 64.1 years old and 75.7% of patients were males. Eighty-three patients (1.34%) presented with MC: 44 (0.71%) experienced a FWR, 17 (0.27%) a PMR, and 22 (0.36%) a VSR. Global rates of MC were 0.82%, 1.43%, 1.24% and 5.07% in the four groups of pre-hospital delays - 0 to 12 h, 12 to 24 h, 24 to 36 h and 36 to 48 h - respectively (p < 0.001). In-hospital mortality rates were high: 44.2%, 47.1% and 54.6% for FWR, PMR and VSR, respectively. In multivariate analysis, factors independently related to the occurrence of MC were older age, female sex, simultaneous COVID-19 infection, absence of dyslipidemia, initial TIMI flow 0 or 1 in the culprit artery, 36 to 48 h-pre-hospital delay and absence of revascularization by percutaneous coronary intervention (PCI) with stent implantation.Conclusion: The probability of MC in STEMI increases with pre-hospital delay. Mechanical complications of STEMI remain associated with a very poor prognosis

Risk Stratification in Transthyretin Cardiac Amyloidosis: The Added Value of Lung Spirometry

: Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized disease that often results in heart failure and death. Traditionally, biological staging systems are used to stratify disease severity. Reduced aerobic capacity has recently been described as useful in identifying higher risk of cardiovascular events and death. Assessment of lung volume via simple spirometry might also hold prognostic relevance. We aimed to assess the combined prognostic value of spirometry, cardiopulmonary exercise testing (CPET) and biomarker staging in ATTR-CA patients in a multi-parametric approach. We retrospectively reviewed patient records with pulmonary function and CPET testing. Patients were followed until study endpoint (MACE: composite of heart-failure-related hospitalization and all-cause death) or censure (1 April 2022). In total, 82 patients were enrolled. Median follow-up was 9 months with 31 (38%) MACE. Impaired peak VO2 and forced vital capacity (FVC) were independent predictors of MACE-free survival, with peak VO2 &lt; 50% and FVC &lt; 70% defining the highest risk group (HR 26, 95% CI: 5-142, mean survival: 15 months) compared to patients with the lowest risk (peak VO2 ≥ 50% and FVC ≥ 70%). Combined peak VO2, FVC and ATTR biomarker staging significantly improved MACE prediction by 35% compared to ATTR staging alone, with 67% patients reassigned a higher risk category (p &lt; 0.01). In conclusion, combining functional and biological markers might synergistically improve risk stratification in ATTR-CA. Integrating simple, non-invasive and easily applicable CPET and spirometry in the routine management of ATTR-CA patients might prove useful for improved risk prediction, optimized monitoring and timely introduction of newer-generation therapies

Prognostic value of cardiopulmonary exercise testing in cardiac amyloidosis

International audienceAims: In amyloid patients, cardiac involvement dramatically worsens functional capacity and prognosis. We sought to study how the cardiopulmonary exercise test (CPET) could help in functional assessment and risk stratification of patients with cardiac amyloidosis (CA).Methods and results: We carried out a multicentre study including patients with light chain (AL) or transthyretin (TTR) CA. All patients underwent exhaustive examination including CPET and follow-up. The primary prognostic endpoint was the occurrence of death or heart failure hospitalization. Overall, 150 patients were included (91 AL and 59 TTR CA). Median age, systolic blood pressure, N-terminal pro B-type natriuretic peptide (NT-proBNP) and cardiac troponin T were 70 (64-78) years, 121 [interquartile range (IQR) 109-139] mmHg, 2806 (IQR 1218-4638) ng/L and 64 (IQR 33-120) ng/L, respectively. New York Heart Association classes were I-II in 64%. Median peak oxygen consumption (VO2 ) and circulatory power were low at 13.0 (10.0-16.9) mL/kg/min and 1730 (1318-2614) mmHg/mL/min, respectively. The minute ventilation/carbon dioxide production slope was increased to 37 (IQR 33-45). A total of 77 patients (51%) had chronotropic insufficiency. After a median follow-up of 20 months, there were 37 deaths and 44 heart failure hospitalizations. At multivariate Cox analysis, peak VO2 ≤13 mL/kg/min [hazard ratio (HR) 2.7, 95% confidence interval (CI) 1.6-4.8], circulatory power ≤1730 mmHg/mL/min (HR 2.4, 95% CI 1.2-4.6) and NT-proBNP ≥1800 ng/L (HR 2.2, 95% CI 1.1-4.3) were found to be associated with the primary outcome. No events occurred in patients with both peak VO2 >13 mL/kg/min and NT-proBNP <1800 ng/L, while the association of VO2 ≤13 mL/kg/min with NT-proBNP ≥1800 ng/L identified a very high-risk subgroup.Conclusion: In CA, CPET is helpful in assessing functional capacity, circulatory and chronotropic responses as well as the prognosis of patients along with cardiac biomarkers

Crest maturation at the cardiomyocyte surface contributes to a new late postnatal development stage that controls the diastolic function of the adult heart

Abstract RATIONALE In addition to its typical rod-shape, the mammalian adult cardiomyocyte (CM) harbors a unique lateral membrane surface architecture with periodic crests, relying on the presence of subsarcolemmal mitochondria (SSM) the role of which is still unknown. OBJECTIVE To investigate the development and functional role of CM crests during the postnatal period. METHODS AND RESULTS Electron/confocal microscopy and western-blot of left ventricular tissues from rat hearts indicated a late CM surface crest maturation, between postnatal day 20 (P20) and P60, as shown by substantial SSM swelling and increased claudin-5 cell surface expression. The P20-P60 postnatal stage also correlates with an ultimate maturation of the T-Tubules and the intercalated disk. At the cellular level, we identified an atypical CM hypertrophy characterized by an increase in long- and short-axes without myofibril addition and with sarcomere lateral stretching, indicative of lateral stretch-based CM hypertrophy. We confirmed the P20-P60 hypertrophy at the organ level by echocardiography but also demonstrated a transcriptomic program after P20 targeting all the cardiac cell populations. At the functional level, using Doppler echocardiography, we found that the P20-P60 period is specifically dedicated to the improvement of relaxation. Mechanistically, using CM-specific knock-out mice, we identified ephrin-B1 as a determinant of CM crest maturation after P20 controlling lateral CM stretch-hypertrophy and relaxation. Interestingly, while young adult Efnb1 CMspe−/− mice essentially show a relaxation impairment with exercise intolerance, they progressively switch toward heart failure with 100% KO mice dying after 13 months. CONCLUSIONS This study highlights a new late P20-P60 postnatal developmental stage of the heart in rodents during which the CM surface crests mature through an ephrin-B1-dependant mechanism and regulate the diastolic function. Moreover, we demonstrate for the first time that the CM crest architecture is cardioprotective

Ephrin-B1 regulates the adult diastolic function through a late postnatal maturation of cardiomyocyte surface crests

The rod-shaped adult cardiomyocyte (CM) harbors a unique architecture of its lateral surface with periodic crests, relying on the presence of subsarcolemmal mitochondria (SSM) with unknown role. Here, we investigated the development and functional role of CM crests during the postnatal period. We found in rodents that CM crest maturation occurs late between postnatal day 20 (P20) and P60 through both SSM biogenesis, swelling and crest-crest lateral interactions between adjacent CM, promoting tissue compaction. At the functional level, we showed that the P20-P60 period is dedicated to the improvement of relaxation. Interestingly, crest maturation specifically contributes to an atypical CM hypertrophy of its short axis, without myofibril addition, but relying on CM lateral stretching. Mechanistically, using constitutive and conditional CM-specific knock-out mice, we identified ephrin-B1, a lateral membrane stabilizer, as a molecular determinant of P20-P60 crest maturation, governing both the CM lateral stretch and the diastolic function, thus highly suggesting a link between crest maturity and diastole. Remarkably, while young adult CM-specific Efnb1 KO mice essentially exhibit an impairment of the ventricular diastole with preserved ejection fraction and exercise intolerance, they progressively switch toward systolic heart failure with 100% KO mice dying after 13 months, indicative of a critical role of CM-ephrin-B1 in the adult heart function. This study highlights the molecular determinants and the biological implication of a new late P20-P60 postnatal developmental stage of the heart in rodents during which, in part, ephrin-B1 specifically regulates the maturation of the CM surface crests and of the diastolic function

Cardiovascular Characteristics and Outcomes of Young Patients with COVID-19

International audienceAlthough 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 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

COVID-19 severity in kidney transplant recipients is similar to nontransplant patients with similar comorbidities

International audienceHigher rates of severe COVID-19 have been reported in kidney transplant recipients (KTRs) compared to nontransplant patients. We aimed to determine if poorer outcomes were specifically related to chronic immunosuppression or underlying comorbidities. We used a 1:1 propensity score-matching method to compare survival and severe disease-free survival (defined as death and/or need for intensive care unit [ICU]) incidence in hospitalized KTRs and nontransplant control patients between February 26 and May 22, 2020. Patients were matched for risk factors of severe COVID-19: age, sex, body mass index, diabetes mellitus, preexisting cardiopathy, chronic lung disease, and basal renal function. We included 100 KTRs (median age [interquartile range (IQR)]) 64.7 years (55.3-73.1) in three French transplant centers. After a median follow-up of 13 days (7-30), transfer to ICU was required for 34 patients (34%) and death occurred in 26 patients (26%). Overall, 43 patients (43%) developed a severe disease during a median follow-up of 8.5 days (2-14). Propensity score matching to a large French cohort of 2017 patients hospitalized in 24 centers, revealed that survival was similar between KTRs and matched nontransplant patients with respective 30-day survival of 62.9% and 71% (p = .38) and severe disease-free 30-day survival of 50.6% and 47.5% (p = .91). These findings suggest that severity of COVID-19 in KTRs is related to their associated comorbidities and not to chronic immunosuppression

History of heart failure in patients with coronavirus disease 2019: Insights from a French registry

International audienceBackground: Although cardiovascular comorbidities seem to be strongly associated with worse outcomes in patients with coronavirus disease 2019 (COVID-19), data regarding patients with preexisting heart failure are limited.Aims: To investigate the incidence, characteristics and clinical outcomes of patients with COVID-19 with a history of heart failure with preserved or reduced ejection fraction.Methods: We performed an observational multicentre study including all patients hospitalized for COVID-19 across 24 centres in France from 26 February to 20 April 2020. The primary endpoint was a composite of in-hospital death or need for orotracheal intubation.Results: Overall, 2809 patients (mean age 66.4±16.9years) were included. Three hundred and seventeen patients (11.2%) had a history of heart failure; among them, 49.2% had heart failure with reduced ejection fraction and 50.8% had heart failure with preserved ejection fraction. COVID-19 severity at admission, defined by a quick sequential organ failure assessment score>1, was similar in patients with versus without a history of heart failure. Before and after adjustment for age, male sex, cardiovascular comorbidities and quick sequential organ failure assessment score, history of heart failure was associated with the primary endpoint (hazard ratio [HR]: 1.41, 95% confidence interval [CI]: 1.06-1.90; P=0.02). This result seemed to be mainly driven by a history of heart failure with preserved ejection fraction (HR: 1.61, 95% CI: 1.13-2.27; P=0.01) rather than heart failure with reduced ejection fraction (HR: 1.19, 95% CI: 0.79-1.81; P=0.41).Conclusions: History of heart failure in patients with COVID-19 was associated with a higher risk of in-hospital death or orotracheal intubation. These findings suggest that patients with a history of heart failure, particularly heart failure with preserved ejection fraction, should be considered at high risk of clinical deterioration

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

International audienceObjective 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 .Clinical trial registration NCT05063097