Acute complication posttransplant: primary allograft dysfunction.

PURPOSE OF REVIEW: Heart transplant is the gold standard treatment for patients with end-stage heart failure, improving both quality of life and survival. Despite advances in donor and recipient management, primary graft dysfunction (PGD) remains the most common cause of morbidity and mortality in the early posttransplant period. This review summarizes recent discoveries in the underlying pathophysiology, risk prediction and management of PGD. RECENT FINDINGS: The incidence of PGD appears to be rising and it is not clear whether this is due to better recognition or secular changes in transplant practice. The utilization of donation after circulatory death organs for transplant is a further consideration for the development of PGD. Organ transport systems and preservation techniques may help to prevent PGD. As some of the risk factors for developing PGD remain modifiable, we summarize the current evidence for prevention and management of PGD. SUMMARY: A better understanding will allow us to appropriately manage donors and recipients to reduce the complex interactions that lead to PGD. The development of an international consortium provides the opportunity for deep phenotyping and development of contemporary risk prediction models for PGD, which may reduce the incidence and consequent early mortality associated with heart transplantation.

Clonal hematopoiesis confers an increased mortality risk in orthotopic heart transplant recipients.

Novel risk stratification and non-invasive surveillance methods are needed in orthotopic heart transplant (OHT) to reduce morbidity and mortality post-transplant. Clonal hematopoiesis (CH) refers to the acquisition of specific gene mutations in hematopoietic stem cells linked to enhanced inflammation and worse cardiovascular outcomes. The purpose of this study was to investigate the association between CH and OHT. Blood samples were collected from 127 OHT recipients. Error-corrected sequencing was used to detect CH-associated mutations. We evaluated the association between CH and acute cellular rejection, CMV infection, cardiac allograft vasculopathy (CAV), malignancies, and survival. CH mutations were detected in 26 (20.5%) patients, mostly in DNMT3A, ASXL1, and TET2. Patients with CH showed a higher frequency of CAV grade 2 or 3 (0% vs. 18%, p < .001). Moreover, a higher mortality rate was observed in patients with CH (11 [42%] vs. 15 [15%], p = .008) with an adjusted hazard ratio of 2.9 (95% CI, 1.4-6.3; p = .003). CH was not associated with acute cellular rejection, CMV infection or malignancies. The prevalence of CH in OHT recipients is higher than previously reported for the general population of the same age group, with an associated higher prevalence of CAV and mortality.

The effect of antiplatelet therapy on survival and cardiac allograft vasculopathy following heart transplantation: A systematic review and meta-analysis.

Cardiac allograft vasculopathy (CAV) is mediated by endothelial inflammation, platelet activation and thrombosis. Antiplatelet therapy may prevent the development of CAV. This systematic review and meta-analysis summarizes and appraises the evidence on the effect of antiplatelet therapy after heart transplantation (HT). CENTRAL(Ovid), MEDLINE(Ovid), Embase(Ovid) were searched from inception until April 30, 2020. Outcomes included CAV, all-cause mortality, and CAV-related mortality. Data were pooled using random-effects models. Seven observational studies including 2023 patients, mean age 52 years, 22% female, 47% with ischemic cardiomyopathy followed over a mean 7.1 years proved eligible. All studies compared acetylsalicylic acid (ASA) to no treatment and were at serious risk of bias. Data from 1911 patients in 6 studies were pooled in the meta-analyses. The evidence is very uncertain about the effect of ASA on all-cause or CAV-related mortality. ASA may reduce the development of CAV (RR 0.75, 95% CI: 0.44-1.29) based on very low certainty evidence. Two studies that conducted propensity-weighted analyses showed further reduction in CAV with ASA (HR 0.31, 95% CI: 0.13-0.74). In conclusion, there is limited evidence that ASA may reduce the development of CAV. Definitive resolution of the impact of antiplatelet therapy on CAV and mortality will require randomized clinical trials.

Value of Invasive Hemodynamic Assessments in Patients Supported by Continuous-Flow Left Ventricular Assist Devices.

Left ventricular assist devices (LVADs) are increasingly used in patients with end-stage heart failure (HF). There is a significant risk of HF admissions and hemocompatibility-related adverse events that can be minimized by optimizing the LVAD support. Invasive hemodynamic assessment, which is currently underutilized, allows personalization of care for patients with LVAD, and may decrease the need for recurrent hospitalizations. It also aids in triaging patients with persistent low-flow alarms, evaluating reversal of pulmonary vasculature remodeling, and assessing right ventricular function. In addition, it can assist in determining the precipitant for residual HF symptoms and physical limitation during exercise and is the cornerstone of the assessment of myocardial recovery. This review provides a comprehensive approach to the use of invasive hemodynamic assessments in patients supported with LVADs.

The Effect of Using a Remote Patient Management Platform in Optimizing Guideline-Directed Medical Therapy in Heart Failure Patients: A Randomized Controlled Trial.

BACKGROUND: Guideline-directed medical therapy (GDMT) remains underutilized in patients with heart failure with reduced ejection fraction, leading to morbidity and mortality. OBJECTIVES: The Medly Titrate (Use of Telemonitoring to Facilitate Heart Failure Mediation Titration) study was an open-label, randomized controlled trial to determine whether remote medication titration for patients with heart failure with reduced ejection fraction was more effective than usual care (UC). METHODS: In this study, 108 patients were randomized to remote GDMT titration through the Medly heart failure program (n = 56) vs UC (n = 52). The primary outcome was the proportion of patients completing GDMT titration at 6 months. Secondary outcomes included the number of clinic visits and time required to achieve titration, patient health outcomes, and health care utilization, including urgent clinic/emergency department visits and hospitalization. RESULTS: At 6 months, GDMT titration was completed in 82.1% (95% CI: 71.2%-90.8%) of patients in the intervention arm vs 53.8% in UC (95% CI: 41.1%-67.7%; P = 0.001). Remote titration required fewer in-person (1.62 ± 1.09 vs 2.42 ± 1.65; P = 0.004) and virtual clinic visits (0.50 ± 1.08 vs 1.29 ± 1.86; P = 0.009) to complete titration. Median time to optimization was shorter with remote titration (3.42 months [Q1-Q3: 2.99-4.04 months] vs 5.47 months [Q1-Q3: 4.14-7.33 months]; P < 0.001). The number of urgent clinic/emergency department visits (incidence rate ratio of remote vs control groups: 0.90 [95% CI: 0.53-1.56]; P = 0.70) were similar between groups, with a reduction in all-cause hospitalization with remote titration (incidence rate ratio: 0.55 [95% CI: 0.31-0.97]; P = 0.042). CONCLUSIONS: Remote titration of GDMT in heart failure with reduced ejection fraction was effective, safe, feasible, and increased the proportion of patients achieving target doses, in a shorter period of time with no excess adverse events compared with UC. (Use of Telemonitoring to Facilitate Heart Failure Mediation Titration [Medly Titrate]; NCT04205513).

Pulmonary Artery Catheter Usage and Impact on Mortality in Patients With Cardiogenic Shock: Results From a Canadian Single-Centre Registry.

BACKGROUND: Hemodynamic assessment for cardiogenic shock (CS) phenotyping in patients has led to renewed interest in the use of pulmonary artery catheters (PACs). METHODS: We included patients admitted with CS from January 2014 to December 2020 and compared clinical outcomes among patients who received PACs and those who did not. The primary outcome was the rate of in-hospital mortality. Secondary outcomes included use of advanced heart failure therapies and coronary intensive care unit (CICU) and hospital lengths of stay. RESULTS: A total of 1043 patients were analysed and 47% received PACs. Patients selected for PAC-guided management were younger and had lower left ventricular function. They also had higher use of vasopressor and inotropes, and 15.2% of them were already supported with temporary mechanical circulatory support (MCS). In-hospital mortality was lower in patients who received PACs (29.3% vs 36.2%; P = 0.02), mainly driven by a reduction in mortality among those in Society for Cardiovascular Angiography and Interventions (SCAI) stages D and E CS. Patients who received PACs were more likely to receive temporary MCS with Impella, durable ventricular assist devices (VADs), or orthotopic heart transplantation (OHT) (P < 0.001 for all analyses). CICU and hospital lengths of stay were longer in patients who used PACs. CONCLUSIONS: Among patients with CS, the use of PACs was associated with lower in-hospital mortality, especially among those in SCAI stages D and E. Patients who received PACs were also more frequently rescued with temporary MCS or received advanced heart failure therapies, such as durable VADs or OHT.

Decoding cardiogenic shock: assessing shock index and its variants as prognostic indicators for in-hospital mortality.

BACKGROUND: Cardiogenic shock (CS) is associated with high in-hospital mortality. Objective assessment of its severity and prognosis is paramount for timely therapeutic interventions. This study aimed to evaluate the efficacy of the shock index (SI) and its variants as prognostic indicators for in-hospital mortality. METHODS: A retrospective study involving 1282 CS patients were evaluated. Baseline patient characteristics, clinical trajectory, hospital outcomes, and shock indices were collected and analysed. Receiver operating characteristic (ROC) curves were employed to determine the predictive accuracy of shock indices in predicting in-hospital mortality. RESULTS: Of those evaluated, 866 (67.6%) survived until discharge. Non-survivors were older (66.0 ± 13.7 vs. 57.4 ± 16.2, P < 0.001), had a higher incidence of cardiac risk factors, and were more likely to present with acute coronary syndrome (33.4% vs. 16.1%, P < 0.001) and out-of-hospital cardiac arrest (11.3% vs. 5.3%, P < 0.001). All mean shock indices were significantly higher in non-survivors compared with survivors. ROC curves demonstrated that adjusted shock index (ASI), age-modified shock index (AMSI), and shock index-C (SIC) had the highest predictive accuracy for in-hospital mortality, with AUC values of 0.654, 0.667, and 0.659, respectively. Subgroup analysis revealed that SIC had good predictive ability in patients with STEMI (AUC: 0.714) and ACS (AUC: 0.696) while AMSI and ASI were notably predictive in the OHCA group (AUC: 0.707 and 0.701, respectively). CONCLUSIONS: Shock index and its variants, especially ASI, AMSI, and SIC, may be helpful in predicting in-hospital mortality in CS patients. Their application could guide clinicians in upfront risk stratification. SIC, ASI, and AMSI show potential in predicting in-hospital mortality in specific CS subsets (STEMI and OHCA). This is the first study to evaluate SI and its variants in CS patients.

Prognostic echocardiographic findings in patients supported with venoarterial extracorporeal membrane oxygenation for cardiogenic shock.

AIMS: Echocardiography is critical in the management of patients supported with veno-arterial extracorporeal membrane oxygenation (V-A ECMO). This study aimed to identify the incidence of critical echocardiographic findings and determine their prognostic significance. METHODS AND RESULTS: All available echocardiograms, hemodynamic variables and outcomes of patients with CS supported with V-A in the period of 2011-2018 at the Toronto General Hospital were retrospectively reviewed. Critical echocardiographic findings were defined as minimal to no left ventricular (LV) ejection, the presence of intra-cardiac clot, significant pericardial effusion and malpositioning of ECMO cannulae. 130 patients were included in this study with in-hospital mortality of 58.5%. Critical findings were most often seen in the first echocardiogram (42/121; 35%). The incidence of critical findings in the first echocardiogram was minimal to no LV ejection in 28 patients (23%), intracardiac thromboses in 8 patients (6.6%), tamponade in 5 patients (4%) and malpositioned cannulae in 1 patient (0.8%). Presence of a critical finding in the first study was associated with an odds ratio for in-hospital mortality of 2.32 (95% CI 1.01-5.06, P = 0.011). CONCLUSION: The initial echocardiogram was most likely to demonstrate a critical finding of which the most common was minimal to no LV ejection. Critical echocardiographic findings carried prognostic significance for in-hospital mortality.

Association of duration and intensity of exercise with phenotypic expression in hypertrophic cardiomyopathy.

OBJECTIVES: There is limited data regarding the impact of exercise on phenotypic expression in hypertrophic cardiomyopathy (HCM). We aimed to investigate whether such an association exists in a cohort of genotype-positive HCM patients. METHODS: In this cross-sectional study of genotype-positive HCM families, we used structured questionnaires to obtain data regarding intensity and duration of exercise of participants starting at the age of 10, as well as data regarding exercise recommendations and their impact on quality of life (QOL). The association of cumulative metabolic-equivalent hours of exercise at different ages with different measures of phenotypic expression (maximal wall thickness, left atrial diameter, extent of late gadolinium enhancement) was analyzed. RESULTS: The study included 109 patients from 55 families, including 43 male (39%) and 90 (83%) phenotype-positive. No association was identified between exercise duration or intensity with any of the phenotypic markers with the exception of greater cumulative exercise associated with younger age at presentation. Similar results were obtained when analysis was limited to exercise until the age of 20, until the age of 30 or only after 30. Among phenotype-positive patients, 89% recalled receiving recommendations regarding exercise restriction, 29% noted reduction in exercise level following such recommendations and 25% noted this having a significant impact on their QOL. CONCLUSION: We found no association between exercise intensity or duration and phenotypic expression in genotype-positive HCM patients. These findings are important for physician-patient discussions and support the recent trend towards more permissive exercise restrictions in HCM.

Improved mortality and haemodynamics with milrinone in cardiogenic shock due to acute decompensated heart failure.

AIMS: Studies in cardiogenic shock (CS) often have a heterogeneous population of patients, including those with acute myocardial infarction and acute decompensated heart failure (ADHF-CS). The therapeutic profile of milrinone may benefit patients with ADHF-CS. We compared the outcomes and haemodynamic trends in ADHF-CS receiving either milrinone or dobutamine. METHODS AND RESULTS: Patients presenting with ADHF-CS (from 2014 to 2020) treated with a single inodilator (milrinone or dobutamine) were included in this study. Clinical characteristics, outcomes, and haemodynamic parameters were collected. The primary endpoint was 30 day mortality, with censoring at the time of transplant or left ventricular assist device implantation. A total of 573 patients were included, of which 366 (63.9%) received milrinone and 207 (36.1%) received dobutamine. Patients receiving milrinone were younger, had better kidney function, and lower lactate at admission. In addition, patients receiving milrinone received mechanical ventilation or vasopressors less frequently, whereas a pulmonary artery catheter was more frequently used. Milrinone use was associated with a lower adjusted risk of 30 day mortality (hazard ratio = 0.52, 95% confidence interval 0.35-0.77). After propensity-matching, the use of milrinone remained associated with a lower mortality (hazard ratio = 0.51, 95% confidence interval 0.27-0.96). These findings were associated with improved pulmonary artery compliance, stroke volume, and right ventricular stroke work index. CONCLUSIONS: The use of milrinone compared with dobutamine in patients with ADHF-CS is associated with lower 30 day mortality and improved haemodynamics. These findings warrant further study in future randomized controlled trials.

Clinical Significance of Postoperative Atrial Fibrillation in Hypertrophic Cardiomyopathy Patients Undergoing Septal Myectomy.

BACKGROUND: The optimal management of hypertrophic cardiomyopathy (HCM) patients with postoperative atrial fibrillation (POAF) after surgical myectomy remains unknown. We sought to investigate the association between POAF and atrial fibrillation (AF) or cardioembolic events during follow-up to bridge this gap. METHODS: Patients undergoing surgical myectomy at 2 HCM referral centres in North America from 2002 to 2020 were included in this study. Patients with preoperative AF were excluded. POAF was defined as any episode of AF within 30 days after surgery. RESULTS: Of 1176 patients, 375 (31.9%) had POAF. Age (adjusted hazard ratio [HR] 1.05, 95% confidence interval [CI] 1.03-1.06; P < 0.001), premyectomy left atrial diameter (LAD; adjusted HR 1.6, 95% CI 1.32-2.02; P < 0.001), and smoking (adjusted HR 1.60, 95% CI 1.17-2.20; P = 0.001) were associated with POAF on multivariable analysis. Of 934 patients with follow-up data, of duration 4.3 ± 4.1 years, AF was detected in 86 (9.2%). Only POAF (HR 4.20, 95% CI 2.44-7.23; P < 0.001), previous history of stroke (HR 4.81, 95% CI 1.63-14.17; P = 0.01), and postmyectomy LAD (HR 1.80, 95% CI 1.21-2.70; P = 0.004) were associated with AF incidence during follow-up. Cardioembolic events occurred in only 15 patients (1.6%). POAF was not associated with increased cardioembolic risk, with only 3 patients with POAF suffering such an event, all more than 4 years after surgery. CONCLUSIONS: POAF is common in HCM patients undergoing myectomy and is a predictor of AF during follow-up. Over long-term follow-up, cardioembolic events are uncommon. These findings suggest that routine long-term anticoagulation for all HCM patients with postmyectomy AF is not justified after the initial postoperative period.

Long-term reduced functional capacity and quality of life in hospitalized COVID-19 patients.

Background: Persistent symptoms and exercise intolerance have been reported after COVID-19, even months after the acute disease. Although, the long-term impact on exercise capacity and health-related quality of life (HRQoL) is still unclear. Research question: To assess the long-term functional capacity and HRQoL in patients hospitalized due to COVID-19. Study design and methods: This is a prospective cohort study, conducted at two centers in Brazil, that included post-discharge COVID-19 patients and paired controls. The cohort was paired by age, sex, body mass index and comorbidities, using propensity score matching in a 1:3 ratio. Patients were eligible if signs or symptoms suggestive of COVID-19 and pulmonary involvement on chest computed tomography. All patients underwent cardiopulmonary exercise testing (CPET) and a HRQoL questionnaire (SF-36) 6 months after the COVID-19. The main outcome was the percentage of predicted peak oxygen consumption (ppVO2). Secondary outcomes included other CPET measures and HRQoL. Results: The study sample comprised 47 post-discharge COVID-19 patients and 141 healthy controls. The mean age of COVID-19 patients was 54 ± 14 years, with 19 (40%) females, and a mean body mass index of 31 kg/m2 (SD, 6). The median follow-up was 7 months (IQR, 6.5-8.0) after hospital discharge. PpVO2 in COVID-19 patients was lower than in controls (83% vs. 95%, p = 0.002) with an effect size of 0.38 ([95%CI], 0.04-0.70). Mean peak VO2 (22 vs. 25 mL/kg/min, p = 0.04) and OUES (2,122 vs. 2,380, p = 0.027) were also reduced in the COVID-19 patients in comparison to controls. Dysfunctional breathing (DB) was present in 51%. HRQoL was significantly reduced in post COVID patients and positively correlated to peak exercise capacity. Interpretation: Hospitalized COVID-19 patients presented, 7 months after discharge, with a reduction in functional capacity and HRQoL when compared to historical controls. HRQoL were reduced and correlated with the reduced peak VO2 in our population.

Digital Technology Application for Improved Responses to Health Care Challenges: Lessons Learned From COVID-19.

While COVID-19 is still ongoing and associated with more than 5 million deaths, the scope and speed of advances over the past year in terms of scientific discovery, data dissemination, and technology have been staggering. It is not a matter of "if" but "when" we will face the next pandemic, and how we leverage technology and data management effectively to create flexible ecosystems that facilitate collaboration, equitable care, and innovation will determine its severity and scale. The aim of this review is to address emerging challenges that came to light during the pandemic in health care and innovations that enabled us to adapt and continue to care for patients. The pandemic highlighted the need for seismic shifts in care paradigms and technology with considerations related to the digital divide and health literacy for digital health interventions to reach full potential and improve health outcomes. We discuss advances in telemedicine, remote patient monitoring, and emerging wearable technologies. Despite the promise of digital health, we emphasise the importance of addressing its limitations, including interpretation challenges, accuracy of findings, and artificial intelligence-driven algorithms. We summarise the most recent recommendation of the Virtual Care Task Force to scaling virtual medical services in Canada. Finally, we propose a model for optimal implementation of health digital innovations with 5 tenets including data management, data security, digital biomarkers, useful artificial intelligence, and clinical integration.

Prediction, prevention, and management of right ventricular failure after left ventricular assist device implantation: A comprehensive review.

Left ventricular assist devices (LVADs) are increasingly common across the heart failure population. Right ventricular failure (RVF) is a feared complication that can occur in the early post-operative phase or during the outpatient follow-up. Multiple tools are available to the clinician to carefully estimate the individual risk of developing RVF after LVAD implantation. This review will provide a comprehensive overview of available tools for RVF prognostication, including patient-specific and right ventricle (RV)-specific echocardiographic and hemodynamic parameters, to provide guidance in patient selection during LVAD candidacy. We also offer a multidisciplinary approach to the management of early RVF, including indications and management of right ventricular assist devices in this setting to provide tools that help managing the failing RV.

CALL-K score: predicting the need for renal replacement therapy in cardiogenic shock.

AIMS: The clinical predictors and outcomes of patients with cardiogenic shock (CS) requiring renal replacement therapy (RRT) have not been studied previously. This study assesses the impact of RRT on mortality in patients with CS and aims to identify clinical factors that contribute to the need of RRT. METHODS AND RESULTS: Consecutive patients presenting with CS were included from a prospective registry of cardiac intensive care unit admissions at a single institution between 2014 and 2020. Of the 1030 patients admitted with CS, 123 (11.9%) received RRT. RRT was associated with higher 1-year mortality [adjusted hazard ratio = 1.62, 95% confidence interval (CI) 1.02-2.14], and a higher in-hospital incidence of sepsis [risk ratio = 2.76, P < 0.001], and pneumonia (risk ratio = 2.9, P = 0.001). Those who received RRT were less likely to receive guideline-directed medical treatment at time of discharge, undergo heart transplantation (2.4% vs. 11.5%, P = 0.002) or receive a durable left ventricular assist device (0.0% vs. 11.6%, P < 0.001). Five variables at admission best predicted the need for RRT (age, lactate, haemoglobin, use of pre-admission loop diuretics, and admission estimated glomerular filtration rate) and were used to generate the CALL-K 9-point risk score, with better discrimination than creatinine alone (P = 0.008). The score was internally validated (area under the curve = 0.815, 95% CI 0.739-0.835) with good calibration (Hosmer-Lemeshow P = 0.827). CONCLUSIONS: RRT is associated with worse outcomes, including a lower likelihood to receive advanced heart failure therapies in patients with CS. A risk score comprising five variables routinely collected at admission can accurately estimate the risk of needing RRT.

Patient Outcomes and Characteristics in a Contemporary Quaternary Canadian Cardiac Intensive Care Unit.

Background: The modern-day cardiac intensive care unit (CICU) has evolved to care for patients with acute critical cardiac illness. We describe the current population of cardiac patients in a quaternary CICU. Methods: Consecutive CICU patients admitted to the CICU at the Toronto General Hospital from 2014 to 2020 were studied. Patient demographics, admission diagnosis, critical care resources, complications, in-hospital mortality, and CICU and hospital length of stay were recorded. Results: A total of 8865 consecutive admissions occurred, with a median age of 64.9 years. The most common primary cardiac diagnoses were acute decompensated heart failure (17.8%), non ST-elevation myocardial infarction (16.8%), ST-elevation myocardial infarction (15.5%), and arrhythmias (14.7%). Cardiogenic shock was seen in 13.2%, and out-of-hospital cardiac arrest in 4.1%. A noncardiovascular admission diagnosis accounted for 13.9% of the cases. Over the period studied, rates of admission were higher for cardiogenic shock (P < 0.001 for trend), with a higher use of critical care resources. Additionally, rates of admission were higher in female patients and those who had chronic kidney disease and diabetes. The in-hospital mortality rate of all CICU admissions was 13.2%, and it was highest in those with noncardiac conditions, compared to the rate in those with cardiac diagnoses (29.4% vs 10.6%, P < 0.001). Conclusions: Given the trends of higher acuity of patients with cardiac critical illness, with higher use of critical care resources, education streams for critical care within cardiology, and alternative pathways of care for patients who have lower-acuity cardiac disease remain imperative to manage this evolving population.

Introduction: L'unité de soins intensifs de cardiologie (USIC) d'aujourd'hui a évolué vers des soins aux patients atteints d'une maladie cardiaque aiguë en phase critique. Nous décrivons la population actuelle de patients cardiaques d'une USIC quaternaires. Méthodes: Les patients consécutifs d'USIC admis à l'USIC de l'Hôpital général de Toronto de 2014 à 2020 ont fait l'objet de l'étude. Les données démographiques des patients, le diagnostic à l'admission, les ressources en soins aux patients en phase critique, les complications, la mortalité intrahospitalière, et la durée de séjour à l'hôpital et à l'USIC ont été enregistrés. Résultats: Il y a eu un total de 8 865 admissions consécutives dont les patients avaient un âge médian de 64,9 ans. Les diagnostics principaux les plus fréquents de maladies cardiaques étaient l'insuffisance cardiaque aiguë décompensée (17,8 %), l'infarctus du myocarde sans élévation du segment ST (16,8 %), l'infarctus du myocarde avec élévation du segment ST (15,5 %) et les arythmies (14,7 %). Le choc cardiogénique a été observé chez 13,2 %, et l'arrêt cardiaque hors de l'hôpital, chez 4,1 %. Un diagnostic d'admission de maladie non cardiovasculaire représente 13,9 % des cas. Durant la période étudiée, les taux d'admission en raison d'un choc cardiogénique étaient plus élevés (P < 0,001 pour la tendance), et entraînaient une utilisation plus élevée de ressources en soins aux patients en phase critique. De plus, les taux d'admission étaient plus élevés chez les patientes, et chez ceux qui avaient une insuffisance rénale chronique et un diabète. Le taux de mortalité intrahospitalière de toutes les admissions à l'USIC était de 13,2 %, et il constituait le taux le plus élevé chez ceux qui avaient des maladies non cardiaques comparativement au taux chez ceux qui avaient des diagnostics de maladies cardiaques (29,4 % vs 10,6 %, P < 0,001). Conclusions: Compte tenu des tendances d'accroissement de la gravité de l'état des patients atteints d'une maladie cardiaque en phase critique et de la plus grande utilisation des ressources en soins aux patients en phase critique, des volets de formation en soins aux patients en phase critique en cardiologie et d'autres protocoles de soins des patients qui ont une maladie cardiaque de plus faible gravité demeurent essentiels à la prise en charge de cette population grandissante.

Clonal haematopoiesis is associated with higher mortality in patients with cardiogenic shock.

AIMS: Cardiogenic shock (CS) with variable systemic inflammation may be responsible for patient heterogeneity and the exceedingly high mortality rate. Cardiovascular events have been associated with clonal haematopoiesis (CH) where specific gene mutations in haematopoietic stem cells lead to clonal expansion and the development of inflammation. This study aims to assess the prevalence of CH and its association with survival in a population of CS patients in a quaternary centre. METHODS AND RESULTS: We compared the frequency of CH mutations among 341 CS patients and 345 ambulatory heart failure (HF) patients matched for age, sex, ejection fraction, and HF aetiology. The association of CH with survival and levels of circulating inflammatory cytokines was analysed. We detected 266 CH mutations in 149 of 686 (22%) patients. CS patients had a higher prevalence of CH-related mutations than HF patients (odds ratio 1.5; 95% confidence interval [CI] 1.0-2.1, p = 0.02) and was associated with decreased survival (30 days: hazard ratio [HR] 2.7; 95% CI 1.3-5.7, p = 0.006; 90 days: HR 2.2; 95% CI 1.3-3.9, p = 0.003; and 3 years: HR 1.7; 95% CI 1.1-2.8, p = 0.01). TET2 or ASXL1 mutations were associated with lower survival in CS patients at all time-points (p ≤ 0.03). CS patients with TET2 mutations had higher circulating levels of SCD40L, interferon-γ, interleukin-4, and tumour necrosis factor-α (p ≤ 0.04), while those with ASXL1 mutations had decreased levels of CCL7 (p = 0.03). CONCLUSIONS: Cardiogenic shock patients have high frequency of CH, notably mutations in TET2 and ASXL1. This was associated with reduced survival and dysregulation of circulating inflammatory cytokines in those CS patients with CH.

Juguloarterial endothelin-1 gradients after severe traumatic brain injury.

BACKGROUND: Endothelin-1 (ET-1) is a potent vasoconstrictor and is thought to be responsible for secondary ischemia and vasogenic edema after traumatic brain injury (TBI). Both CSF and plasma concentrations have been shown to be increased after TBI, but there is little evidence to confirm an intracranial site of production. METHODS: Using paired arterial and jugular venous bulb sampling, we measured arterial and jugular levels of ET-1 and its precursor, big endothelin (Big ET), and calculated juguloarterial (JA) gradients for the first 5 days post-TBI. RESULTS: Arterial levels of both Big ET and ET-1 were maximal on day 1 post-TBI, and decreased thereafter (P < 0.05). Arterial levels of Big ET and ET-1 showed correlation across all 5 days of the study (r(2) = 0.25, P < 0.001). While there was no significant JA gradient for Big ET, significant gradients were observed for ET-1 on days 1-4 post-TBI (P < 0.05). There was no correlation between JA gradients for Big ET and ET-1 (r(2) < 0.1, P > 0.9). These data suggest parenchymal production of ET-1 by brain tissue with spill over into the blood, rather than local intraluminal cleavage of Big ET in the cerebral vasculature. Systemic ET-1 levels and JA gradients of ET-1 were unrelated to the injury severity, APACHE II score, Marshall Grade, the presence of subarachnoid or subdural hemorrhage, or eventual outcome. CONCLUSIONS: These findings confirm the synthesis of Big ET and its cleavage to ET-1 within the brain after TBI. More work is needed to elucidate the pathophysiological role and the outcome impact of ET-1 generation after TBI.