Use of the Win Ratio Analysis in Critical Care Trials.

Composite outcomes are commonly used in critical care trials to estimate the treatment effect of an intervention. A significant limitation of classical analytic approaches is that they assign equal statistical importance to each component in a composite, even if these do not have the same clinical importance (i.e., in a composite of death and organ failure, death is clearly more important). The win ratio (WR) method has been proposed as an alternative for trial outcomes evaluation, as it effectively assesses events based on their clinical relevance (i.e., hierarchical order) by comparing each patient in the intervention group with their counterparts in the control group. This statistical approach is increasingly used in cardiovascular outcome trials. However, WR may be useful to unveil treatment effects also in the critical care setting, because these trials are typically moderately sized, thus limiting the statistical power to detect small differences between groups, and often rely on composite outcomes that include several components of different clinical importance. Notably, the advantages of this approach may be offset by several drawbacks (such as ignoring ties and difficulties in selecting and ranking endpoints) and challenges in appropriate clinical interpretation (i.e., establishing clinical meaningfulness of the observed effect size). In this perspective article, we present some key elements to implementing WR statistics in critical care trials, providing an overview of strengths, drawbacks, and potential applications of this method. To illustrate, we conduct a reevaluation of the HYPO-ECMO (Hypothermia during Venoarterial Extracorporeal Membrane Oxygenation) trial using the WR framework as a case example.

MASLD and MASH at the crossroads of hepatology trials and cardiorenal metabolic trials.

Steatotic liver disease (SLD) is a worldwide public health problem, causing considerable morbidity and mortality. Patients with SLD are at increased risk for major adverse cardiovascular (CV) events, type 2 diabetes mellitus and chronic kidney disease. Conversely, patients with cardiometabolic conditions have a high prevalence of SLD. In addition to epidemiological evidence linking many of these conditions, there is evidence of shared pathophysiological processes. In December 2022, a unique multi-stakeholder, multi-specialty meeting, called MOSAIC (Metabolic multi Organ Science Accelerating Innovation in Clinical Trials) was convened to foster collaboration across metabolic, hepatology, nephrology and CV disorders. One of the goals of the meeting was to consider approaches to drug development that would speed regulatory approval of treatments for multiple disorders by combining liver and cardiorenal endpoints within a single study. Non-invasive tests, including biomarkers and imaging, are needed in hepatic and cardiorenal trials. They can be used as trial endpoints, to enrich trial populations, to diagnose and risk stratify patients and to assess treatment efficacy and safety. Although they are used in proof of concept and phase 2 trials, they are often not acceptable for regulatory approval of therapies. The challenge is defining the optimal combination of biomarkers, imaging and morbidity/mortality outcomes and ensuring that they are included in future trials while minimizing the burden on patients, trialists and trial sponsors. This paper provides an overview of some of the wide array of CV, liver and kidney measurements that were discussed at the MOSAIC meeting.

High Risk of Stroke in Patients With Worsening Heart Failure, Reduced Ejection Fraction, Coronary Heart Disease and Sinus Rhythm: Risk Prediction Score Analysis From the COMMANDER-HF Trial.

BACKGROUND: Patients with heart failure with reduced ejection fraction (HFrEF) and sinus rhythm have a heightened risk of stroke. Whether anticoagulation benefits these patients is uncertain. In this post hoc analysis of the A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction, or Stroke in Participants with Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure (COMMANDER-HF) trial we evaluated how a previously validated risk model consisting of 3 variables (history of prior stroke, insulin-treated diabetes, and N-terminal pro-B-type natriuretic peptide level) would perform, compared with plasma d-dimer, for stroke prediction and estimation of the benefit of low-dose rivaroxaban. METHODS AND RESULTS: Stroke risk and treatment effect were computed across risk score and plasma d-dimer tertiles. Risk score was available in 58% of the COMMANDER-HF population (n = 2928). Over a median follow-up of 512 days (range 342-747 days), 60 patients experienced a stroke (14.6 per 1000 patient-years). The risk model did not identify patients at higher risk of stroke and showed a low overall prognostic performance (C-index = 0.53). The effect of rivaroxaban on stroke was homogeneous across risk score tertiles (P-interaction = .67). Among patients in whom the risk score was estimated, d-dimer was available in 2343 (80%). d-dimer had an acceptable discrimination performance for stroke prediction (C-index = 0.66) and higher plasma d-dimer concentrations were associated with higher rates of stroke (ie, tertile 3 vs tertile 1, hazard ratio 3.65, 95% confidence interval 1.59-8.39, P = .002). Treatment with low-dose rivaroxaban reduced the incidence of stroke in patients at highest risk by d-dimer levels (ie, >515 ng/mL, hazard ratio 0.42, 95% confidence interval 0.18-0.95, P-interaction = .074), without any safety concerns. CONCLUSIONS: In our analysis, plasma d-dimer concentrations performed better than a previously described 3-variable risk score for stroke prediction in patients with heart failure with reduced ejection fraction, a recent clinical worsening and sinus rhythm as enrolled in the COMMANDER-HF trial. In these patients, a raised plasma d-dimer concentration identified patients who might benefit most from rivaroxaban.

When to use spironolactone, eplerenone or finerenone in the spectrum of cardiorenal diseases.

Kidney disease frequently coexists with cardiovascular (CV) diseases, and this dual presence significantly amplifies the risk of adverse clinical outcomes. Shared pathophysiological mechanisms and common CV risk factors contribute to the increased expression of mineralocorticoid receptors, which in turn can drive the progression of chronic CV-kidney disorders. The steroidal mineralocorticoid receptor antagonists (MRAs) spironolactone and eplerenone have demonstrated efficacy in improving patient outcomes in cases of heart failure with reduced ejection fraction or after a myocardial infarction, but have limited value in patients with chronic kidney disease. The non-steroidal MRA finerenone has now established itself as a foundational guideline-recommended therapy in patients with diabetic kidney disease. To date, these pharmacological agents have been developed in distinct patient populations. The consequences of their distinct pharmacological profiles necessitate further consideration. They have not undergone testing across the entire spectrum of cardiorenal scenarios, and the evidence base is currently being complemented with ongoing trials. In this review, we aim to synthesize the existing body of evidence and chart the future trajectory for the use of spironolactone, eplerenone and finerenone in improving clinical outcomes across the diverse spectrum of cardiorenal diseases. By consolidating the current state of knowledge, we seek to provide valuable insights for informed decision making in the management of patients with these complex and interconnected conditions.

Dietary inflammatory potential and arterial stiffness in a French cohort: Insights from the STANISLAS study.

BACKGROUND AND AIMS: Chronic inflammation plays a key role in arterial stiffness pathogenesis. Dietary components can display anti- or pro-inflammatory properties. Nonetheless, the association between the diet's overall inflammatory potential and arterial stiffness is unclear. This study aimed to assess the association between the diet's overall inflammatory potential and arterial stiffness assessed by carotid-femoral pulse wave velocity (cfPWV). METHODS AND RESULTS: This cross-sectional study included 1307 participants from the STANISLAS family cohort study. Dietary data were collected using a validated food frequency questionnaire. The adapted dietary inflammatory index (ADII) score was calculated to assess the inflammatory potential of the participants' diet. The association of ADII score quartile with cfPWV was assessed using IPW-weighted linear mixed models with random family effect. The median (Q1-Q3) ADII score was 0.45 (-1.57, 2.04). Participants exhibiting higher ADII scores demonstrated elevated energy intake, dietary saturated fat, and ultra-processed foods. Conversely, individuals with lower ADII scores exhibited higher vitamins and omega intakes, and a higher diet quality, as assessed by the DASH score. Despite these observations from the descriptive analyses, ADII score quartiles were not significantly associated with cfPWV (ß(95% CI) were 0.01 (-0.02,0.04) for Q2, 0.02 (-0.01,0.05) for Q3, and 0.02 (-0.01,0.05) for Q4 compared to Q1). CONCLUSION: In this cross-sectional study, participants had a relatively modest consumption of pro-inflammatory foods, no substantial associations were observed between the diet inflammatory potential and arterial stiffness. Further longitudinal studies in larger cohorts are needed to better understand the link between inflammatory diet and arterial stiffness.

Ventricular-arterial coupling and cardiovascular risk among young adults: The African-PREDICT study.

Ventricular-arterial coupling (VAC) has independent diagnostic and prognostic value for cardiovascular (CV) risk stratification, but studies on its association with anthropometric and CV factors are sparse in young individuals without overt CV disease. We aim to provide descriptive data regarding VAC and its associations with CV risk factors in young adults without overt CV disease. For 631 (mean age, 24 ± 3 yr; 51% female) individuals, VAC was determined by carotid-femoral pulse wave velocity (PWV)/global longitudinal strain (GLS). Multivariable logistic and linear regression models were performed to explore the association between PWV/GLS and CV risk factors. A P-value < 0.05 was considered statistically significant. The mean PWV/GLS was 0.33 ± 0.07 m/s%. Higher ratios of PWV/GLS associated with older age, male sex, and a higher prevalence of CV risk factors (i.e., higher blood pressure, prevalent hypertension, higher waist circumference, active smoking, higher plasma triglycerides, lower high-density lipoprotein cholesterol, and an adverse urine albumin/creatinine ratio). Furthermore, higher PWV/GLS was associated with echocardiographic measures such as lower ejection fraction and higher left ventricle mass index. In expanded logistic regression models, higher ratios of PWV/GLS were significantly associated with the prevalence of active smoking [odds ratio (OR), 1.88; confidence interval (CI) 1.36-2.58, P < 0.001] and hypertension (OR 1.98; CI 1.40-2.80, P < 0.001). We demonstrated that worse VAC reflected by higher values of PWV/GLS are significantly associated with CV risk factors in young adults. The results suggest that PWV/GLS might serve as a tool to improve the profiling of cardiovascular risk in young adults.NEW & NOTEWORTHY Assessing VAC is especially useful in heart failure and valvular heart disease, but less is known about VAC in the pathophysiology of CV disease risk in younger individuals. In young individuals without overt CV disease, we showed descriptive data regarding VAC, determined by PWV/GLS ratio, and explored the associations of VAC with clinical CV disease risk factors. Worse VAC, reflected by higher values of PWV/GLS, associated with high blood pressure and smoking in young adults.

SGLT2 inhibition in heart failure with reduced or preserved ejection fraction: Finding the right patients to treat.

Sodium-glucose transport inhibitors (SGLT2i) are effective in heart failure (HF) with ejection fraction (EF) <40% (referred to as HF with reduced EF - HFrEF) and left ventricular EF (LVEF) >40%. Current evidence suggests that SGLT2i should be initiated across a large spectrum of EFs and renal function in patients with HF and with and without diabetes. We reviewed the benefits of SGLT2i in the entire spectrum of HF and provided some clues that may guide physicians in their strategy of initiating and maintaining SGLT2i (with or without SGLT1i effect) therapy. Taken together, the evidence thus far arises from an array of trials performed in different settings (acute/chronic), risk categories, and phenotypes of HF (HFrEF/HFpEF), and in addition to the most common HF therapies, supports the homogenous effect of SGLT2i across a large spectrum of patients with HF. SGLT2i appear to be effective and well-tolerated drugs in the majority of clinical HF scenarios, regardless of LVEF, estimated glomerular filtration rate, diabetic status or the level of the acuteness of the clinical setting. Therefore, most patients with HF should be treated with SGLT2i. However, in the face of the therapeutic inertia that has been observed in HF over the past decades, the actual implementation of SGLT2i in routine practice remains the most significant challenge.

Validation of the MEDIA echo score for the prognosis of heart failure with preserved ejection fraction.

There is currently no widely used prognostic score in heart failure (HF) with preserved ejection fraction (HFpEF). The MEDIA echo score, including four variables (pulmonary arterial systolic pressure > 40 mmHg, inferior vena cava collapsibility index < 50%, average E/e' > 9, and lateral mitral annular s' < 7 cm/s), has been proposed as a useful risk stratification tool. This study aimed at further validating the MEDIA echo score in both hospitalised and ambulatory HFpEF patients. The MEDIA echo score ranges from 0 to 4 (each criterion scores 1 point). The associations between MEDIA echo score and cardiovascular outcomes were assessed in two independent HFpEF cohorts, namely patients hospitalised for worsening HFpEF (N = 242, mean age 78 ± 11), and stable ambulatory HFpEF patients (N = 76, mean age 65 ± 8). Using multivariable Cox models, in the worsening HFpEF cohort, patients with a MEDIA echo score of 3-4 displayed a significant increased risk of death (HR 2.10, 95%CI 1.02-4.33, P = 0.043, score 0-1 as reference). In the ambulatory HFpEF cohort, patients with a MEDIA echo score of 2 had a significantly higher risk of death or HF hospitalisation (HR 3.44, 95%CI 1.27-9.30, P = 0.015, score 0 as reference), driven by HF hospitalisation; in that cohort, adding the MEDIA echo score to the clinical model significantly improved reclassification for the combined endpoint (integrated discrimination improvement 6.2%, P = 0.006). The MEDIA echo score significantly predicted the outcome of HFpEF patients in both hospital and ambulatory settings; its use may help refine routine risk stratification on top of well-established prognosticators in stable HFpEF patients.

Performance of Early Capillary Refill Time Measurement on Outcomes in Cardiogenic Shock: An Observational, Prospective Multicentric Study.

Rationale: Identification of cardiogenic shock severity is a critical step to adapt the management level upon admission. Peripheral tissue perfusion signs, simple and reliable markers of tissue hypoperfusion have never been extensively assessed during cardiogenic shock. Objectives: To assess the correlation of capillary refill time values with 90-day mortality in cardiogenic shock patients or the need for venoarterial extracorporeal membrane oxygenation (VA-ECMO) support. Also to assess the correlation between capillary refill time and hemodynamic parameters. Methods: All consecutive patients with cardiogenic shock admitted to the intensive care unit of two tertiary teaching hospitals were included in a prospective observational study. Macro-hemodynamic parameters (such as heart rate, blood pressure, left ventricular ejection fraction, and cardiac index) and peripheral tissue perfusion signs, such as capillary refill time on the index fingertip, mottling, and Pv-aCO2 (the difference between partial pressure of CO2 between venous and arterial blood) were recorded at inclusion (0 hour), 6 hours, 12 hours, 24 hours, and 48 hours. The composite primary endpoint was the association between 90-day mortality or the need for VA-ECMO support. Measurements and Main Results: A total of 61 patients were included; at inclusion, simplified acute physiology score II was 64 (52-77) points. The primary endpoint was met by 42% of patients. Capillary refill time values were significantly higher at all time points in nonsurvivors or patients needing VA-ECMO support. In univariate analysis, capillary refill time > 3 seconds at inclusion was associated with 90-day all-cause mortality or VA-ECMO support (hazard ratio, 12.38; 95% confidence interval, 2.91-52.71). Capillary refill time at inclusion was poorly associated with macrocirculatory parameters but significantly correlated with microcirculatory parameters. Further, capillary refill time added incremental value to Cardshock score, with an AUC combination at 0.93. Conclusions: In patients with cardiogenic shock admitted to the ICU, our preliminary data suggest that a prolonged capillary refill time >3 seconds was associated with an early prediction of 90-day mortality or the need for VA-ECMO support.

Sodium-glucose co-transporter 2 inhibitors in heart failure: an updated evidence-based practical guidance for clinicians.

The sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to reduce risks of clinical events in patients with heart failure (HF), with early and sustained benefits regardless of ejection fraction, diabetic status, and care setting. As part and parcel of the modern foundational HF therapy, clinicians should be familiar with these drugs, in order to implement their use and limit the potential adverse effects. We present an up-to-date review of current evidence and a practical guide for the prescription of SGLT2 inhibitors in patients with HF, highlighting important elements for patient selection, treatment initiation, dosing, and problem solving.

Association between kidney retransplantation and survival according to age in the French national cohort of dialysis patients.

The mean age of patients returning to dialysis after a first kidney transplantation (KT) has increased in the past decades. We aimed to assess the association between second KT (2KT) and survival according to age at the time of return to dialysis. Data of 5334 patients registered in the French Renal Epidemiology and Information Network (REIN) (mean age 56.6 ± 13.6 years) who returned to dialysis after a first KT were collected. The association of 2KT with death was assessed using a propensity score-based analysis taking into account baseline and follow-up variables. In relisted patients (3272 patients, 61.3%), retransplantation was associated with better overall survival in comparison with patients who remained in dialysis (adjusted HR 0.75 [0.63-0.89], p = .0009). The survival advantage conferred by retransplantation gradually declined with increasing age (adjusted HR 0.41 [0.24-0.70] in patients <50, HR 0.94 (0.69-1.27) in patients aged 70 or older, p for interaction 0.034 for age considered as a continuous variable). 2KT is associated with better survival as opposed to remaining on dialysis after a first kidney graft failure. Nevertheless, this survival benefit is age dependent and diminishes with increasing age. The risk/benefit ratio should be comprehensively assessed in the oldest patients when relisting is considered.

Heart failure in obesity: insights from proteomics in patients treated with or without weight-loss surgery.

BACKGROUND: Obesity is associated with incident heart failure (HF), but the underlying mechanisms are unclear. METHODS: We performed a nested case-control study within the Swedish-Obese-Subjects study, by identifying 411 cases who developed HF and matched them with respect to age, sex, weight-loss-surgery and length of follow-up with 410 controls who did not develop HF. In analyses corrected for multiple testing, we studied 182 plasma proteins known to be related to cardiovascular disease to investigate whether they could add to the understanding of the processes underlying obesity-related HF. RESULTS: A total of 821 subjects were followed for 16 ± 6 years. Multivariable analysis adjusted for matching variables revealed that 32 proteins were significantly associated with HF. Twelve proteins were related to HF ≥ 80% of the time using a bootstrap resampling approach (false-discovery-rate [FDR] < 0.05): 11 were associated with increased HF-risk: TNFRSF10A*, ST6GAL1, PRCP, MMP12, TIMP1, CCL3, QPCT, ANG, C1QTNF1, SERPINA5 and GAL-9; and one was related to reduced HF-risk: LPL. An further 20 proteins were associated with onset of HF 50-80% of the time using bootstrap resampling (FDR < 0.05). A pathway analysis including all significant 32 proteins suggested that these biomarkers were related to inflammation, matrix remodeling, cardiometabolic hormones and hemostasis. Three proteins, C1QTNF1, FGF-21 and CST3, reflecting dyslipidemia and kidney disease, displayed a higher association with HF in patients who did not undergo weight-loss-surgery and maintained with obesity. CONCLUSION: Pathways associated with HF in obesity include inflammation, matrix remodeling, cardiometabolic hormones and hemostasis; three protein biomarkers predicting HF appeared to be obesity-specific.

The Effect of Spironolactone in Patients With Obesity at Risk for Heart Failure: Proteomic Insights from the HOMAGE Trial.

BACKGROUND: Adipose tissue influences the expression and degradation of circulating biomarkers. We aimed to identify the biomarker profile and biological meaning of biomarkers associated with obesity to assess the effect of spironolactone on the circulating biomarkers and to explore whether obesity might modify the effect of spironolactone. METHODS AND RESULTS: Protein biomarkers (n = 276) from the Olink Proseek-Multiplex cardiovascular and inflammation panels were measured in plasma collected at baseline, 1 month and 9 months from the HOMAGE randomized controlled trial participants. Of the 510 participants, 299 had obesity defined as an increased waist circumference (≥102 cm in men and ≥88 cm in women). Biomarkers at baseline reflected adipogenesis, increased vascularization, decreased fibrinolysis, and glucose intolerance in patients with obesity at baseline. Treatment with spironolactone had only minor effects on this proteomic profile. Obesity modified the effect of spironolactone on systolic blood pressure (Pinteraction = 0.001), showing a stronger decrease of blood pressure in obese patients (-14.8 mm Hg 95% confidence interval -18.45 to -11.12) compared with nonobese patients (-3.6 mm Hg 95% confidence interval -7.82 to 0.66). CONCLUSIONS: Among patients at risk for heart failure, those with obesity have a characteristic proteomic profile reflecting adipogenesis and glucose intolerance. Spironolactone had only minor effects on this obesity-related proteomic profile, but obesity significantly modified the effect of spironolactone on systolic blood pressure.

Metabolic Syndrome and the Risk of Preclinical Heart Failure: Insights after 17 Years of Follow-Up from the STANISLAS Cohort.

BACKGROUND: We used data from people initially free of clinical cardiovascular disease to evaluate the association between metabolic syndrome (MS) and incident preclinical heart failure (pHF). METHODS AND RESULTS: STANISLAS was a familial, single-center, longitudinal prospective cohort study composed of 1,006 families from Nancy, France (median follow-up, 17 years [1993-2016]). Age- and sex-adjusted logistic regression and inverse probability weighting models were used to evaluate the association between MS and pHF, which was defined by diastolic dysfunction, atrial enlargement, ventricular hypertrophy, or elevated natriuretic peptides. Among 944 people who were adults at the first and final visit, those with baseline MS were more likely to be older (63 vs. 61 vs. 59 years of age) and male (73% vs. 55% vs. 45%) compared to people who developed incident MS and people who had no baseline MS, respectively. Furthermore, compared to people without baseline MS, the risk of pHF was numerically larger among people with baseline MS (adjusted odds ratio [aOR] 2.27, 95% CI: 1.07-4.81) and people who developed incident MS (aOR 1.56, 95% CI: 1.00-2.43). Concerning the metabolic determinants of MS, the risk of pHF was most elevated in people with baseline hypertension (aOR 3.19, 95% CI: 1.80-5.63) and elevated waist circumference (aOR 2.59, 95% CI: 1.47-4.57). CONCLUSION: Overall, HF is an important public health concern given the high risk of mortality when patients with MS or elevated fasting glucose become established with the disease. Early aggressive lifestyle modification and medical intervention among patients free of cardiovascular disease with an obese-hypertensive phenotype may be warranted to prevent HF development.

Inductive database to support iterative data mining: Application to biomarker analysis on patient data in the Fight-HF project.

Machine learning is now an essential part of any biomedical study but its integration into real effective Learning Health Systems, including the whole process of Knowledge Discovery from Data (KDD), is not yet realised. We propose an original extension of the KDD process model that involves an inductive database. We designed for the first time a generic model of Inductive Clinical DataBase (ICDB) aimed at hosting both patient data and learned models. We report experiments conducted on patient data in the frame of a project dedicated to fight heart failure. The results show how the ICDB approach allows to identify biomarker combinations, specific and predictive of heart fibrosis phenotype, that put forward hypotheses relative to underlying mechanisms. Two main scenarios were considered, a local-to-global KDD scenario and a trans-cohort alignment scenario. This promising proof of concept enables us to draw the contours of a next-generation Knowledge Discovery Environment (KDE).

The effect of spironolactone on cardiovascular function and markers of fibrosis in people at increased risk of developing heart failure: the heart 'OMics' in AGEing (HOMAGE) randomized clinical trial.

AIMS: To investigate the effects of spironolactone on fibrosis and cardiac function in people at increased risk of developing heart failure. METHODS AND RESULTS: Randomized, open-label, blinded-endpoint trial comparing spironolactone (50 mg/day) or control for up to 9 months in people with, or at high risk of, coronary disease and raised plasma B-type natriuretic peptides. The primary endpoint was the interaction between baseline serum galectin-3 and changes in serum procollagen type-III N-terminal pro-peptide (PIIINP) in participants assigned to spironolactone or control. Procollagen type-I C-terminal pro-peptide (PICP) and collagen type-1 C-terminal telopeptide (CITP), reflecting synthesis and degradation of type-I collagen, were also measured. In 527 participants (median age 73 years, 26% women), changes in PIIINP were similar for spironolactone and control [mean difference (mdiff): -0.15; 95% confidence interval (CI) -0.44 to 0.15 µg/L; P = 0.32] but those receiving spironolactone had greater reductions in PICP (mdiff: -8.1; 95% CI -11.9 to -4.3 µg/L; P < 0.0001) and PICP/CITP ratio (mdiff: -2.9; 95% CI -4.3 to -1.5; <0.0001). No interactions with serum galectin were observed. Systolic blood pressure (mdiff: -10; 95% CI -13 to -7 mmHg; P < 0.0001), left atrial volume (mdiff: -1; 95% CI -2 to 0 mL/m2; P = 0.010), and NT-proBNP (mdiff: -57; 95% CI -81 to -33 ng/L; P < 0.0001) were reduced in those assigned spironolactone. CONCLUSIONS: Galectin-3 did not identify greater reductions in serum concentrations of collagen biomarkers in response to spironolactone. However, spironolactone may influence type-I collagen metabolism. Whether spironolactone can delay or prevent progression to symptomatic heart failure should be investigated.

Effect of Moderate Hypothermia vs Normothermia on 30-Day Mortality in Patients With Cardiogenic Shock Receiving Venoarterial Extracorporeal Membrane Oxygenation: A Randomized Clinical Trial.

IMPORTANCE: The optimal approach to the use of venoarterial extracorporeal membrane oxygenation (ECMO) during cardiogenic shock is uncertain. OBJECTIVE: To determine whether early use of moderate hypothermia (33-34 °C) compared with strict normothermia (36-37 °C) improves mortality in patients with cardiogenic shock receiving venoarterial ECMO. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial of patients (who were eligible if they had been endotracheally intubated and were receiving venoarterial ECMO for cardiogenic shock for <6 hours) conducted in the intensive care units at 20 French cardiac shock care centers between October 2016 and July 2019. Of 786 eligible patients, 374 were randomized. Final follow-up occurred in November 2019. INTERVENTIONS: Early moderate hypothermia (33-34 °C; n = 168) for 24 hours or strict normothermia (36-37 °C; n = 166). MAIN OUTCOMES AND MEASURES: The primary outcome was mortality at 30 days. There were 31 secondary outcomes including mortality at days 7, 60, and 180; a composite outcome of death, heart transplant, escalation to left ventricular assist device implantation, or stroke at days 30, 60, and 180; and days without requiring a ventilator or kidney replacement therapy at days 30, 60, and 180. Adverse events included rates of severe bleeding, sepsis, and number of units of packed red blood cells transfused during venoarterial ECMO. RESULTS: Among the 374 patients who were randomized, 334 completed the trial (mean age, 58 [SD, 12] years; 24% women) and were included in the primary analysis. At 30 days, 71 patients (42%) in the moderate hypothermia group had died vs 84 patients (51%) in the normothermia group (adjusted odds ratio, 0.71 [95% CI, 0.45 to 1.13], P = .15; risk difference, -8.3% [95% CI, -16.3% to -0.3%]). For the composite outcome of death, heart transplant, escalation to left ventricular assist device implantation, or stroke at day 30, the adjusted odds ratio was 0.61 (95% CI, 0.39 to 0.96; P = .03) for the moderate hypothermia group compared with the normothermia group and the risk difference was -11.5% (95% CI, -23.2% to 0.2%). Of the 31 secondary outcomes, 30 were inconclusive. The incidence of moderate or severe bleeding was 41% in the moderate hypothermia group vs 42% in the normothermia group. The incidence of infections was 52% in both groups. The incidence of bacteremia was 20% in the moderate hypothermia group vs 30% in the normothermia group. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial involving patients with refractory cardiogenic shock treated with venoarterial ECMO, early application of moderate hypothermia for 24 hours did not significantly increase survival compared with normothermia. However, because the 95% CI was wide and included a potentially important effect size, these findings should be considered inconclusive. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02754193.

Evidence of a Blood Pressure Reduction During the COVID-19 Pandemic and Associated Lockdown Period: Insights from e-Health Data.

Introduction: Despite widespread investigation into the incidence of acute myocardial infarction during the coronavirus disease 2019 (COVID-19) pandemic and associated lockdown, no study has examined the situation's impact on blood pressure (BP) levels. Methods: Measurements of BP and heart rate (HR) were obtained from persons living in the Paris urban area using connected home BP monitors (accessible to patients and health providers through a secured server). Three time periods of e-health recordings were compared: during the pandemic before the lockdown, during the lockdown, and the same time period in 2019. Results: A total of 297,089 BP recordings from 2,273 participants (age 56.3 ± 12.8 years, 81.1% male) were made. During confinement, systolic BP gradually decreased by 3 mmHg (-2.4 to -3.9), and diastolic BP by 1.5 mmHg (-1.4 to -2.2) (all p < 0.001); this decrease was greater for participants with higher BP (p < 0.0001 each). No significant variation in HR was noted. Conclusion: Among a very large cohort, we observed a significant decrease in home BP measured with e-health devices during the first lockdown period. This study emphasizes the research potential of e-health during the COVID-19 crisis.

SGLT2 Inhibitors in Heart Failure with Reduced Ejection Fraction: A Paradigm Shift Toward Dual Cardio-Renal Protection.

Sodium-glucose transport inhibitors (SGLT2i) have been found to be effective in preventing heart failure in patients with diabetes or chronic kidney disease with or without cardiovascular disease. Recent evidence suggests that SGLT2i substantially improve cardiovascular and renal outcomes in patients with heart failure with reduced ejection fraction (HFrEF). In this review, we discuss the combined cardio-renal benefits of SGLT2i in patients with HFrEF. In addition, we discuss the impact of renoprotection in the midterm management of HFrEF and possible implementation strategies for initiating SGLT2i in routine care of HFrEF.

Correction: Diagnostic performance of congestion score index evaluated from chest radiography for acute heart failure in the emergency department: A retrospective analysis from the PARADISE cohort.

[This corrects the article DOI: 10.1371/journal.pmed.1003419.].