A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy.

AIMS: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients. METHODS AND RESULTS: Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44-9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73-0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92-0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.3% reduction of ICD placements with the same proportion of protected patients (P < 0.001). CONCLUSION: Using the largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICDs (www.arvcrisk.com).

A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy.

AIMS: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients. METHODS AND RESULTS: Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44-9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73-0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92-0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.6% reduction of ICD placements with the same proportion of protected patients (P < 0.001). CONCLUSION: Using the largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICDs (www.arvcrisk.com).

A disease-specific comorbidity index for predicting mortality in patients admitted to hospital with a cardiac condition.

BACKGROUND: Comorbidity indexes derived from administrative databases are essential tools of research in global health. We sought to develop and validate a novel cardiac-specific comorbidity index, and to compare its accuracy with the generic Charlson-Deyo and Elixhauser comorbidity indexes. METHODS: We derived the cardiac-specific comorbidity index from consecutive patients who were admitted to hospital at a tertiary-care cardiology hospital in Quebec. We used logistic regression analysis and incorporated age, sex and 22 clinically relevant comorbidities to build the index. We compared the cardiac-specific comorbidity index with refitted Charlson-Deyo and Elixhauser comorbidity indexes using the C-statistic and net reclassification improvement to predict in-hospital death, and the Akaike information criterion to predict length of stay. We validated our findings externally in an independent cohort obtained from a provincial registry of coronary disease in Alberta. RESULTS: The novel cardiac-specific comorbidity index outperformed the refitted generic Charlson-Deyo and Elixhauser comorbidity indexes for predicting in-hospital mortality in the derivation population (n = 10 137): C-statistic 0.95 (95% confidence interval [CI] 0.94-0.9) v. 0.81 (95% CI 0.77-0.84) and 0.86 (95% CI 0.82-0.89), respectively. In the validation population (n = 17 877), the cardiac-specific comorbidity index was similarly better: C-statistic 0.92 (95% CI 0.89-0.94) v. 0.76 (95% CI 0.71-0.81) and 0.82 (95% CI 0.78-0.86), respectively, and also numerically outperformed the Charlson-Deyo and Elixhauser comorbidity indexes for predicting 1-year mortality (C-statistic 0.78 [95% CI 0.76-0.80] v. 0.75 [95% CI 0.73-0.77] and 0.77 [95% CI 0.75-0.79], respectively). Similarly, the cardiac-specific comorbidity index showed better fit for the prediction of length of stay. The net reclassification improvement using the cardiac-specific comorbidity index for the prediction of death was 0.290 compared with the Charlson-Deyo comorbidity index and 0.192 compared with the Elixhauser comorbidity index. INTERPRETATION: The cardiac-specific comorbidity index predicted in-hospital and 1-year death and length of stay in cardiovascular populations better than existing generic models. This novel index may be useful for research of cardiology outcomes performed with large administrative databases.

Impact of MELD Score-Based Organ Allocation on Mortality, Bleeding, and Transfusion in Liver Transplantation: A Before-and-After Observational Cohort Study.

OBJECTIVE: The goal of this study was to evaluate the effect of the Model for End-Stage Liver Disease (MELD)-based allocation system on mortality, bleeding, and transfusion requirement in orthotopic liver transplantation (OLT). DESIGN: OLTs were studied for this observational study (before-and-after observational cohort study). SETTING: One community hospital. PARTICIPANTS: The study comprised 686 patients who underwent 750 consecutive OLTs. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Patients who underwent OLT in the MELD era had an adjusted lower 1-year mortality (adjusted odds ratio 0.45 [0.24-0.83]) compared with patients who underwent OLT the pre-MELD era. No significant difference in 1-month mortality was observed. Other variables with a significant effect on 1-year mortality in multivariate analysis were preoperative international normalized ratio, intraoperative use of a phlebotomy, total intraoperative volume of crystalloid infused, and retransplantation. Blood loss was greater in the MELD era (median difference 200 mL; p < 0.001), as were red blood cell, fresh frozen plasma, and cryoprecipitate transfusions. More patients in the MELD era received at least 1 transfusion (27% v 20%; p = 0.024). CONCLUSION: The MELD allocation system did not affect 1-month mortality, but a decrease in 1-year mortality was demonstrated. Blood loss and transfusions increased during OLTs performed in the MELD era. The role of other variables should be explored further to explain postoperative morbidity and mortality.

Development of a Predictive Model for Blood Transfusions and Bleeding During Liver Transplantation: An Observational Cohort Study.

OBJECTIVE: Orthotopic liver transplantation (OLT) frequently is associated with major blood loss and considerable transfusion requirements. The goal of this study was to define the risk factors for multiple transfusions and major bleeding during OLT and to help identify higher risk patients that could benefit from targeted interventions. DESIGN: OLTs were studied for this observational cohort study. SETTING: Community hospital. PARTICIPANTS: A total of 800 consecutive OLTs were studied. INTERVENTION: No intervention. MEASUREMENTS AND MAIN RESULTS: Baseline and intraoperative data were gathered. Multivariate logistic regression analyses were performed to find variables associated with 2 outcomes: transfusion of more than 2 units of red blood cells (RBC) and bleeding ≥900 mL. Two nomograms were developed to predict individual risks. The overall intraoperative RBC transfusion was 0.6 ± 1.4 units on average, and 61 surgeries (7.6%) received more than 2 units of RBC (4.5 ± 1.9). Some variables were associated with the outcomes: 5 were associated with transfusion of more than 2 units of RBC (patient's height, starting hemoglobin concentration, starting bilirubin value, the use of a phlebotomy, and central venous pressure [CVP] at the time of vena cava clamping) and 3 with blood loss of ≥900 mL (starting hemoglobin value, Child-Turcotte-Pugh score, and CVP at the time of vena cava clamping). Preclamping CVP showed the strongest association with both outcomes. Nomograms were developed to predict the individual OLT recipients' risk of requiring more than 2 units RBC and suffering from major bleeding. Among the variables associated with multiple RBC transfusions and major bleeding, 3 can lead to interventions: baseline hemoglobin value, the use of a phlebotomy, and the preclamping CVP. CONCLUSION: Some variables were able to predict the risk of multiple transfusions and major bleeding in this low bleeding liver transplantation population. Further studies based on these variables should be done to better define the role of targeted interventions in higher risk liver transplant recipients.

Right Ventricular Depression After Cardiopulmonary Bypass for Valvular Surgery.

OBJECTIVE: To assess if right ventricular (RV) dysfunction is associated with increased mortality after cardiac surgery. DESIGN: Post-hoc analysis of a single-center double-blind randomized controlled trial. SETTING: University hospital. PARTICIPANTS: A total of 120 patients undergoing simple or complex valvular surgery. INTERVENTIONS: Patients were randomized to receive intravenous amiodarone or placebo intraoperatively. As secondary analysis, patients were divided into those requiring or not requiring postoperative inotropic agents. MEASUREMENTS AND MAIN RESULTS: After cardiopulmonary bypass (CPB), there were significant increases in heart rate, cardiac index, systolic and mean arterial pressures, central venous pressure and pulmonary capillary wedge pressure with reduction in systemic vascular resistance (p<0.05). Right ventricular end-systolic area became larger in those without inotropes and tricuspid annular plane systolic excursion was reduced in all patients; mitral annular systolic velocities were higher in patients receiving inotropes. Both right- and left-sided Doppler signals were altered significantly after CPB, which may be attributed to increased filling pressure. Inotropic agents were required in 56 patients after CPB (47%). The use of inotropic agents was associated with increased left and right atrial velocities (p<0.05). There were no differences in postoperative complications between groups; however, the number of deaths at 6 years was increased in patients who received inotropes after CPB (p = 0.0247). CONCLUSIONS: The increases in right-sided dimensions after CPB are associated with reduction in RV function and increased biventricular filling pressure, suggesting worsening biventricular function and interventricular dependence. Inotropic medications were associated with unaltered RV dimensions and increased biatrial activity.

Pulmonary production of osteopontin in humans: effects of left ventricular systolic dysfunction and cardiopulmonary bypass.

Background: We evaluated pulmonary production of osteopontin (OPN) in left ventricular systolic dysfunction (LVSD) and after cardiopulmonary bypass surgery (CPB). OPN is a phosphoglycoprotein involved in inflammation and remodeling. In subjects with LVSD, plasma OPN correlates with prognosis but its origin is unknown. We hypothesized that the lungs produce OPN and that this could be affected by LVSD and CPB.Methods and Results: Subjects with (n =57; left ventricular ejection fraction [LVEF] 32 ± 8%) and without (n = 63; LVEF 59 ± 7%) LVSD were studied during CPB. Arterial and venous OPN plasma levels were determined. Arterial and venous OPN levels were higher in LVSD (P = .0290). For both groups, levels dropped 1 hour after surgery and nearly doubled 24 hours after (P ! .0001 vs basal).Notably, there was a significant positive arteriovenous gradient with arterial levels higher than venous levels. Arteriovenous differences were statistically significant at baseline (P = .0120) and 1 hour (P < .0001) but not at 24 hours (P = .0649). Arterial levels in heart failure correlated inversely with renal function(P = .016) and positively with mean pulmonary pressure (P = .028), heart rate (P = .036), and C-reactive protein (P = .047).Conclusions: There is production of circulating OPN by the lungs, unaffected by LVSD or CPB. This likely represents an overflow from local lung production and does not contribute to increased levels in LVSD or after CPB.

Impact of age on the predictive value of NT-proBNP in patients with diabetes mellitus stabilised after an acute coronary syndrome.

AIMS: To assess the impact of age on the prognostic value of NT-proBNP concentration in patients with type-2 diabetes mellitus (T2DM) stabilised after an Acute Coronary Syndrome (ACS). METHODS: The AleCardio study compared aleglitazar with placebo in 7226 patients with T2DM and recent ACS. Patients with heart failure were excluded. Median follow-up was 104 weeks. Baseline NT-proBNP plasma concentration was measured centrally. Multivariable Cox regression was used to determine the mortality predictive information provided by NT-proBNP across age groups. RESULTS: Median age was 61y (IQR 54, 67). NT-proBNP concentration increased by quartile (Q) of age (median 264, 318, 391, and 588 pg/ml). Compared to Q1, patients in Q4 of NT-proBNP had higher (p < 0.001) adjusted HR for all-cause (aHR 6.9; 95 % CI 4.0-12) and cardiovascular (11; 5.4-23) death. Within each age Q, baseline NT-proBNP in patients who died was 3 times higher than in survivors (all p < 0.001). When age and NT-proBNP levels were modeled as continuous variables, their interaction term was nonsignificant. The relative prognostic information provided by NT-proBNP (percent of total X2) increased from 38 % in age Q1 to 75 % in age Q4 for mortality, and from 50 % to 88 % for CV death. CONCLUSIONS: Among patients with T2DM stabilised after an ACS, NT-proBNP level predicts death irrespective of age.

Antithrombotic Management and Outcomes of Anterior ST-Elevation Myocardial Infarction With New-Onset Wall Motion Abnormalities in Men and Women.

Background: In patients with anterior ST-elevation myocardial infarction (STEMI) and new-onset antero-apical wall motion abnormalities (WMAs), whether the rate of prophylaxis against left ventricular thrombus and outcomes differ between men and women is unknown. Methods: A multicentre retrospective cohort study of patients with STEMI and new-onset antero-apical WMAs treated with primary percutaneous coronary intervention was conducted. Patients with an established indication of oral anticoagulation (OAC) were excluded. The rates of triple therapy (double antiplatelet therapy + OAC) at discharge were compared for women vs men. The rates of net adverse clinical events, a composite of mortality, myocardial infarction, stroke or transient ischemic attack, systemic thromboembolism or Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding at 6 months were compared across sex using a multivariate logistic regression model. Results: A total of 1664 patients were included in the primary analysis, of whom 402 (24.2%) were women and 1262 (75.8%) were men. A total of 138 women (34.3%) and 489 men (38.7%) received a triple therapy prescription at discharge (P = 0.11). At 6 months, 33 women (8.2%) and 96 men (7.6%) experienced a net adverse clinical event (adjusted odds ratio 0.82; 95% confidence interval 0.49-1.37). No difference occurred in the risk of bleeding events and ischemic events between men and women, when these were analyzed separately. Conclusions: The rates of OAC prescription for left ventricular thrombus prophylaxis and clinical outcomes at 6 months were similar in women and men following anterior STEMI with new-onset antero-apical WMAs.

Contexte: On ignore si le taux de prophylaxie contre le thrombus ventriculaire gauche et les résultats thérapeutiques diffèrent entre les hommes et les femmes qui ont subi un infarctus du myocarde avec élévation du segment ST (STEMI) antérieur et ont des anomalies du mouvement pariétal (AMP) antéroapical d'apparition récente. Méthodes: Nous avons mené une étude de cohorte rétrospective multicentrique auprès de patients qui ont subi un STEMI et ont des AMP d'apparition récente traitées par une intervention coronarienne percutanée primaire. Nous avons exclu les patients chez lesquels il existait une indication établie à l'anticoagulation orale (ACO). Nous avons comparé les taux de trithérapie (bithérapie antiplaquettaire + ACO) à la sortie de l'hôpital entre les femmes et les hommes. Nous avons comparé les taux d'événements indésirables cliniques nets, le critère composite de mortalité, d'infarctus du myocarde, d'accident vasculaire cérébral ou d'accident ischémique transitoire, la thromboembolie systémique ou l'hémorragie de type 3 ou 5 selon le Bleeding Academic Research Consortium (BARC) après 6 mois entre les sexes au moyen du modèle de régression logistique multivariée. Résultats: Au sein des 1 664 patients de l'analyse principale, 402 (24,2 %) étaient des femmes et 1262 (75,8 %) étaient des hommes. Un total de 138 femmes (34,3 %) et de 489 hommes (38,7 %) ont reçu une ordonnance de trithérapie à la sortie de l'hôpital (P = 0,11). Après 6 mois, 33 femmes (8,2 %) et 96 hommes (7,6 %) ont subi un événement indésirable net (rapport de cotes ajusté 0,82 ; intervalle de confiance à 95 % 0,49-1,37). Aucune différence n'a été notée dans le risque d'événements hémorragiques et d'événements ischémiques entre les hommes et les femmes lorsque ces événements étaient analysés séparément. Conclusions: Les taux d'ordonnances d'ACO en prophylaxie du thrombus ventriculaire gauche et les résultats cliniques après 6 mois étaient similaires entre les femmes et les hommes à la suite du STEMI antérieur et des AMP antéroapicale d'apparition récente.

Pulmonary production of osteopontin in humans: effects of left ventricular systolic dysfunction and cardiopulmonary bypass.

BACKGROUND: We evaluated pulmonary production of osteopontin (OPN) in left ventricular systolic dysfunction (LVSD) and after cardiopulmonary bypass surgery (CPB). OPN is a phosphoglycoprotein involved in inflammation and remodeling. In subjects with LVSD, plasma OPN correlates with prognosis but its origin is unknown. We hypothesized that the lungs produce OPN and that this could be affected by LVSD and CPB. METHODS AND RESULTS: Subjects with (n = 57; left ventricular ejection fraction [LVEF] 32 ± 8%) and without (n = 63; LVEF 59 ± 7%) LVSD were studied during CPB. Arterial and venous OPN plasma levels were determined. Arterial and venous OPN levels were higher in LVSD (P = .0290). For both groups, levels dropped 1 hour after surgery and nearly doubled 24 hours after (P < .0001 vs basal). Notably, there was a significant positive arteriovenous gradient with arterial levels higher than venous levels. Arteriovenous differences were statistically significant at baseline (P = .0120) and 1 hour (P < .0001) but not at 24 hours (P = .0649). Arterial levels in heart failure correlated inversely with renal function (P = .016) and positively with mean pulmonary pressure (P = .028), heart rate (P = .036), and C-reactive protein (P = .047). CONCLUSIONS: There is production of circulating OPN by the lungs, unaffected by LVSD or CPB. This likely represents an overflow from local lung production and does not contribute to increased levels in LVSD or after CPB.

Adcy9 Gene Inactivation Improves Cardiac Function After Myocardial Infarction in Mice.

BACKGROUND: Polymorphisms in the adenylate cyclase 9 (ADCY9) gene influence the benefits of the cholesteryl ester transfer protein (CETP) modulator dalcetrapib on cardiovascular events after acute coronary syndrome. We hypothesized that Adcy9 inactivation could improve cardiac function and remodelling following myocardial infarction (MI) in absence of CETP activity. METHODS: Wild-type (WT) and Adcy9-inactivated (Adcy9Gt/Gt) male mice, transgenic or not for human CETP (tgCETP+/-), were subjected to MI by permanent left anterior descending coronary artery ligation and studied for 4 weeks. Left ventricular (LV) function was assessed by echocardiography at baseline, 1, and 4 weeks after MI. At sacrifice, blood, spleen and bone marrow cells were collected for flow cytometry analysis, and hearts were harvested for histologic analyses. RESULTS: All mice developed LV hypertrophy, dilation, and systolic dysfunction, but Adcy9Gt/Gt mice exhibited reduced pathologic LV remodelling and better LV function compared with WT mice. There were no differences between tgCETP+/- and Adcy9Gt/Gt tgCETP+/- mice, which both exhibited intermediate responses. Histologic analyses showed smaller cardiomyocyte size, reduced infarct size, and preserved myocardial capillary density in the infarct border zone in Adcy9Gt/Gt vs WT mice. Count of bone marrow T cells and B cells were significantly increased in Adcy9Gt/Gt mice compared with the other genotypes. CONCLUSIONS: Adcy9 inactivation reduced infarct size, pathologic remodelling, and cardiac dysfunction. These changes were accompanied by preserved myocardial capillary density and increased adaptive immune response. Most of the benefits of Adcy9 inactivation were only observed in the absence of CETP.

Contemporary incidence and predictors of left ventricular thrombus in patients with anterior acute myocardial infarction.

BACKGROUND: The incidence of left ventricular thrombus (LVT) after anterior acute myocardial infarction (AMI) has not been well established in the era of primary percutaneous coronary intervention (pPCI) and potent dual antiplatelet therapy. The objective of this study is to establish the contemporary incidence of LVT in this population, to identify their risk factors, and to examine their association with clinical outcomes. METHODS: A multicenter retrospective cohort study including AMI patients with new-onset antero-apical wall motion abnormalities treated with pPCI between 2009 and 2017 was conducted. The primary outcome was LVT during the index hospitalization. Predictors of LVT were identified using multivariate logistic regression. Net adverse clinical events (NACE), a composite of mortality, myocardial infarction, stroke or transient ischemic attack, systemic thromboembolism or BARC type 3 or 5 bleeding at 6 months were compared between the LVT and no LVT groups. RESULTS: Among the 2136 patients included, 83 (3.9%) patients developed a LVT during index hospitalization. A lower left ventricular ejection fraction (LVEF) [adjusted odds ratio (aOR) 0.97; 95% confidence intervals (CI) 0.94-0.99] and the degree of worse anterior WMA (aOR 4.34; 95% CI 2.24-8.40) were independent predictors of LVT. A NACE occurred in 5 (5.72 per 100 patient-year) patients in the LVT group and in 127 (6.71 per 100 patient-year) patients in the no LVT group at 6 months [adjusted hazard ratio (aHR): 0.87; 95% CI 0.35-2.14]. CONCLUSIONS: The risk of LVT after anterior AMI with new-onset wall motion abnormalities is low, but this complication remains present in the contemporary era of timely pPCI and potent dual antiplatelet therapy .

Rationale and Design of the Randomized Bayesian Multicenter COME-TAVI Trial in Patients With a New Onset Left Bundle Branch Block.

Patients with new-onset left bundle branch block (LBBB) after transcatheter aortic valve implantation (TAVI) are at risk of developing delayed high-degree atrioventricular block. Management of new-onset LBBB post-TAVI remains controversial. In the Comparison of a Clinical Monitoring Strategy Versus Electrophysiology-Guided Algorithmic Approach in Patients With a New LBBB After TAVI (COME-TAVI) trial, consenting patients with new-onset LBBB that persists on day 2 after TAVI, meeting exclusion/inclusion criteria, are randomized to an electrophysiological study (EPS)-guided approach or 30-day electrocardiographic monitoring. In the EPS-guided approach, patients with a His to ventricle (HV) interval ≥ 65 ms undergo permanent pacemaker implantation. Patients randomized to noninvasive monitoring receive a wearable continuous electrocardiographic recording and transmitting device for 30 days. Follow-up will be performed at 3, 6, and 12 months. The primary endpoint is a composite outcome designed to capture net clinical benefit. The endpoint incorporates major consequences of both strategies in patients with new-onset LBBB after TAVI, as follows: (i) sudden cardiac death; (ii) syncope; (iii) atrioventricular conduction disorder requiring a pacemaker (for a class I or IIa indication); and (iv) complications related to the pacemaker or EPS. The trial incorporates a Bayesian design with a noninformative prior, outcome-adaptive randomization (initially 1:1), and 2 prespecified interim analyses once 25% and 50% of the anticipated number of primary endpoints are reached. The trial is event-driven, with an anticipated upper limit of 452 patients required to reach 77 primary outcome events over 12 months of follow-up. In summary, the aim of this Bayesian multicentre randomized trial is to compare 2 management strategies in patients with new-onset LBBB post-TAVI-an EPS-guided approach vs noninvasive 30-day monitoring. Trial registration number: NCT03303612.

Les patients chez qui un bloc de branche gauche (BBG) est récemment apparu à la suite de l'implantation valvulaire aortique par cathéter (IVAC) présentent un risque de bloc auriculoventriculaire de haut degré tardif. La prise en charge d'un BBG récemment apparu après une IVAC demeure controversée. Dans le cadre de l'essai COME-TAVI (Comparison of a ClinicalMonitoring Strategy VersusElectrophysiology-Guided Algorithmic Approach in Patients With a New LBBB AfterTAVI, ou comparaison d'une stratégie de surveillance clinique, par rapport à une approche guidée par étude électrophysiologique et fondée sur un algorithme, chez des patients présentant un BBG d'apparition récente à la suite d'une IVAC), des patients qui présentent un BBG d'apparition récente persistant le 2e jour après une IVAC, qui répondent aux critères d'admissibilité et qui ont donné leur consentement sont répartis aléatoirement pour être suivis à l'aide d'une approche guidée par une étude électrophysiologique (EEP) ou faire l'objet d'une surveillance électrocardiographique d'une durée de 30 jours. Un stimulateur cardiaque est implanté chez les patients du groupe de l'EEP dont l'intervalle HV (temps de conduction dans le tronc du faisceau de His jusqu'aux ventricules) est ≥ 65 ms. Les patients du groupe de surveillance non invasive reçoivent un dispositif portable d'enregistrement et de transmission continue de données électrocardiographiques pour une période de 30 jours. Le suivi sera réalisé aux 3e, 6e et 12e mois. Le critère d'évaluation principal est un paramètre composite conçu afin de saisir le bienfait clinique net. Il comprend les conséquences majeures des deux stratégies chez les patients présentant un BBG d'apparition récente après une IVAC, comme suit : (i) mort subite d'origine cardiaque; (ii) syncope; (iii) trouble de la conduction auriculoventriculaire nécessitant la pose d'un stimulateur cardiaque (pour une indication de classe I ou IIa); et (iv) complications relatives au stimulateur cardiaque ou à l'EEP. L'essai intègre une conception bayésienne avec une répartition aléatoire (dans un rapport initial de 1:1) antérieure non informative adaptée aux résultats et deux analyses intermédiaires définies au préalable lorsque 25 % et 50 % du nombre anticipé des critères d'évaluation principaux seront atteints. L'essai est axé sur les événements, et la limite supérieure anticipée pour atteindre 77 événements relatifs aux critères d'évaluation principaux sur 12 mois de suivi est de 452 patients. En résumé, l'objectif de cet essai bayésien multicentrique à répartition aléatoire est de comparer deux stratégies de prise en charge de patients présentant un BBG d'apparition récente après une IVAC, soit une approche guidée par une EEP, par rapport à une surveillance non invasive de 30 jours. Trial registration number: NCT03303612.

Oral Anticoagulation for the Prevention of Thromboembolic Events in Patients With Anterior ST-Segment Elevation Myocardial Infarction.

OBJECTIVES: The objective is to assess the comparative effectiveness and safety of dual-antiplatelet therapy (DAPT) vs triple therapy (TT) with DAPT + oral anticoagulant (OAC) in patients with anterior ST-segment elevation myocardial infarction (STEMI) and with new-onset anterior/apical wall-motion abnormalities (WMAs) treated with primary percutaneous coronary intervention (PCI). BACKGROUND: Patients with STEMI and new-onset anterior/apical WMA may benefit from the addition of OAC to prevent left ventricular thrombus and cardioembolic events. METHODS: A multicenter, retrospective cohort study was conducted. Patients with a concomitant indication for OAC were excluded. Patients discharged on TT were compared with patients discharged on DAPT using adjusted Cox proportional hazards analysis and inverse probability of treatment weighting. The primary endpoint was the net adverse clinical event (NACE) rate at 6 months (composite of all-cause mortality, non-fatal MI, stroke, or transient ischemic attack, systemic thromboembolism or type 3 or 5 Bleeding Academic Research Consortium [BARC] bleeding). RESULTS: A total of 1666 patients were included, among which 627 were treated with TT and 1039 were treated with DAPT. A NACE occurred in 55 patients (6.03 per 100 patient-years) in the TT group and in 74 patients (7.18 per 100 patient-years) in the DAPT group (adjusted hazard ratio, 0.86; 95% confidence interval, 0.55-1.32). Adjusted risk of the individual components of the primary endpoint, ischemic events, and bleeding events were similar between both groups (P>.05 for all). CONCLUSIONS: The addition of OAC to DAPT in anterior STEMI patients with new-onset WMA treated with PCI was not associated with a significant reduction in NACE.

Genetics of symptom remission in outpatients with COVID-19.

We conducted a genome-wide association study of time to remission of COVID-19 symptoms in 1723 outpatients with at least one risk factor for disease severity from the COLCORONA clinical trial. We found a significant association at 5p13.3 (rs1173773; P = 4.94 × 10-8) near the natriuretic peptide receptor 3 gene (NPR3). By day 15 of the study, 44%, 54% and 59% of participants with 0, 1, or 2 copies of the effect allele respectively, had symptom remission. In 851 participants not treated with colchicine (placebo), there was a significant association at 9q33.1 (rs62575331; P = 2.95 × 10-8) in interaction with colchicine (P = 1.19 × 10-5) without impact on risk of hospitalisations, highlighting a possibly shared mechanistic pathway. By day 15 of the study, 46%, 62% and 64% of those with 0, 1, or 2 copies of the effect allele respectively, had symptom remission. The findings need to be replicated and could contribute to the biological understanding of COVID-19 symptom remission.

Colchicine for community-treated patients with COVID-19 (COLCORONA): a phase 3, randomised, double-blinded, adaptive, placebo-controlled, multicentre trial.

BACKGROUND: Evidence suggests a role for excessive inflammation in COVID-19 complications. Colchicine is an oral anti-inflammatory medication beneficial in gout, pericarditis, and coronary disease. We aimed to investigate the effect of colchicine on the composite of COVID-19-related death or hospital admission. METHODS: The present study is a phase 3, randomised, double-blind, adaptive, placebo-controlled, multicentre trial. The study was done in Brazil, Canada, Greece, South Africa, Spain, and the USA, and was led by the Montreal Heart Institute. Patients with COVID-19 diagnosed by PCR testing or clinical criteria who were not being treated in hospital were eligible if they were at least 40 years old and had at least one high-risk characteristic. The randomisation list was computer-generated by an unmasked biostatistician, and masked randomisation was centralised and done electronically through an automated interactive web-response system. The allocation sequence was unstratified and used a 1:1 ratio with a blocking schema and block sizes of six. Patients were randomly assigned to receive orally administered colchicine (0·5 mg twice per day for 3 days and then once per day for 27 days thereafter) or matching placebo. The primary efficacy endpoint was the composite of death or hospital admission for COVID-19. Vital status at the end of the study was available for 97·9% of patients. The analyses were done according to the intention-to-treat principle. The COLCORONA trial is registered with ClinicalTrials.gov (NCT04322682) and is now closed to new participants. FINDINGS: Trial enrolment began in March 23, 2020, and was completed in Dec 22, 2020. A total of 4488 patients (53·9% women; median age 54·0 years, IQR 47·0-61·0) were enrolled and 2235 patients were randomly assigned to colchicine and 2253 to placebo. The primary endpoint occurred in 104 (4·7%) of 2235 patients in the colchicine group and 131 (5·8%) of 2253 patients in the placebo group (odds ratio [OR] 0·79, 95·1% CI 0·61-1·03; p=0·081). Among the 4159 patients with PCR-confirmed COVID-19, the primary endpoint occurred in 96 (4·6%) of 2075 patients in the colchicine group and 126 (6·0%) of 2084 patients in the placebo group (OR 0·75, 0·57-0·99; p=0·042). Serious adverse events were reported in 108 (4·9%) of 2195 patients in the colchicine group and 139 (6·3%) of 2217 patients in the placebo group (p=0·051); pneumonia occurred in 63 (2·9%) of 2195 patients in the colchicine group and 92 (4·1%) of 2217 patients in the placebo group (p=0·021). Diarrhoea was reported in 300 (13·7%) of 2195 patients in the colchicine group and 161 (7·3%) of 2217 patients in the placebo group (p<0·0001). INTERPRETATION: In community-treated patients including those without a mandatory diagnostic test, the effect of colchicine on COVID-19-related clinical events was not statistically significant. Among patients with PCR-confirmed COVID-19, colchicine led to a lower rate of the composite of death or hospital admission than placebo. Given the absence of orally administered therapies to prevent COVID-19 complications in community-treated patients and the benefit of colchicine in patients with PCR-proven COVID-19, this safe and inexpensive anti-inflammatory agent could be considered for use in those at risk of complications. Notwithstanding these considerations, replication in other studies of PCR-positive community-treated patients is recommended. FUNDING: The Government of Quebec, the Bill & Melinda Gates Foundation, the National Heart, Lung, and Blood Institute of the US National Institutes of Health, the Montreal Heart Institute Foundation, the NYU Grossman School of Medicine, the Rudin Family Foundation, and philanthropist Sophie Desmarais.

Association between intraoperative rotational thromboelastometry or conventional coagulation tests and bleeding in liver transplantation: an observational exploratory study.

INTRODUCTION: Liver transplantation is associated with major blood loss and transfusions. Our objective was to evaluate the association between coagulation results (rotational thromboelastometry (ROTEM) and conventional coagulation tests) and intraoperative bleeding or perioperative red blood cell (RBC) transfusions in liver transplantation. METHODS: We measured ROTEM values and conventional coagulation tests at the beginning of surgery, after graft reperfusion and at the end of surgery. We did bivariate correlation and multivariable regression analyses to explore the association between test results and either intraoperative bleeding or perioperative RBC transfusions. RESULTS: We enrolled 75 consecutive patients. Median [Q1-Q3] intraoperative blood loss was 1400 mL [675-2300] and 59% of patients did not receive any RBC transfusion either intraoperatively or postoperatively. In multivariable analyses, FIBTEM maximal clot firmness (MCF) measured at the beginning of surgery was associated with lower intraoperative blood loss (ß = -106 mL for each mm; 95% CI, -203 to -9 mL). Both a higher haemoglobin concentration (multiplicative factor = 0.89 for each g/L; 95% CI, 0.84 to 0.95) and FIBTEM MCF measured at the end of surgery (multiplicative factor = 0.68 for each mm; 95% CI, 0.48 to 0.95) were associated with fewer postoperative RBC transfusions. CONCLUSION: FIBTEM MCF was strongly associated with intraoperative blood loss and postoperative transfusions while other coagulation results were not. This study might inform future clinical trials on ROTEM-based interventions in liver transplantation. STUDY REGISTRATION: Clinical Trials.gov: NCT02356068.

Injection of Bupivacaine into the Pleural and Mediastinal Drains: A Novel Approach for Decreasing Incident Pain After Cardiac Surgery - Montreal Heart Institute Experience.

BACKGROUND: We conducted a chart review of prospectively collected data in order to demonstrate the safety and efficacy of an innovative technique of pleural and mediastinal drain injections. METHODS: Patients who had undergone cardiac surgery and who continued to have pain despite the use of a multimodal pain protocol received injections of 20 mL of 0.25% bupivacaine in pleural and/or mediastinal chest drainage tubes. RESULTS: Patients were evaluated for the incidence mediastinitis, osteitis, and deep sternal wound infection as well as the speed and intensity of pain relief. The odds ratio of infection in the infused group was 0.955 (CI = 0.4705, 1.9384). The adjusted mean "decrease in pain" was 4.01 (SEM = 0.15 and 95% CI = 3.78, 4.38), using the 11-point Likert Numerical Rating Scale. The mean adjusted "time to maximum pain relief" was 8.33 minutes (SEM = 0.42 and 95% CI = 7.50, 9.15). CONCLUSION: This technique is a powerful, safe, and efficient tool in the armamentarium of pain management and its growing use within our institution has provided a substantial benefit in the treatment of early post-operative pain.

Predictors of mortality in hospital survivors with type 2 diabetes mellitus and acute coronary syndromes.

AIM: To define the predictors of long-term mortality in patients with type 2 diabetes mellitus and recent acute coronary syndrome. METHODS AND RESULTS: A total of 7226 patients from a randomized trial, testing the effect on cardiovascular outcomes of the dual peroxisome proliferator-activated receptor agonist aleglitazar in patients with type 2 diabetes mellitus and recent acute coronary syndrome (AleCardio trial), were analysed. Median follow-up was 2 years. The independent mortality predictors were defined using Cox regression analysis. The predictive information provided by each variable was calculated as percent of total chi-square of the model. All-cause mortality was 4.0%, with cardiovascular death contributing for 73% of mortality. The mortality prediction model included N-terminal proB-type natriuretic peptide (adjusted hazard ratio = 1.68; 95% confidence interval = 1.51-1.88; 27% of prediction), lack of coronary revascularization (hazard ratio = 2.28; 95% confidence interval = 1.77-2.93; 18% of prediction), age (hazard ratio = 1.04; 95% confidence interval = 1.02-1.05; 15% of prediction), heart rate (hazard ratio = 1.02; 95% confidence interval = 1.01-1.03; 10% of prediction), glycated haemoglobin (hazard ratio = 1.11; 95% confidence interval = 1.03-1.19; 8% of prediction), haemoglobin (hazard ratio = 1.01; 95% confidence interval = 1.00-1.02; 8% of prediction), prior coronary artery bypass (hazard ratio = 1.61; 95% confidence interval = 1.11-2.32; 7% of prediction) and prior myocardial infarction (hazard ratio = 1.40; 95% confidence interval = 1.05-1.87; 6% of prediction). CONCLUSION: In patients with type 2 diabetes mellitus and recent acute coronary syndrome, mortality prediction is largely dominated by markers of cardiac, rather than metabolic, dysfunction.

Homeostasis Model Assessment of Insulin Resistance and Survival in Patients With Diabetes and Acute Coronary Syndrome.

Objective: Insulin resistance has been linked to development and progression of atherosclerosis and is present in most patients with type 2 diabetes. Whether the degree of insulin resistance predicts adverse outcomes in patients with type 2 diabetes and acute coronary syndrome (ACS) is uncertain. Design: The Effect of Aleglitazar on Cardiovascular Outcomes after Acute Coronary Syndrome in Patients with Type 2 Diabetes Mellitus trial compared the peroxisome proliferator-activated receptor-α/γ agonist aleglitazar with placebo in patients with type 2 diabetes and recent ACS. In participants not treated with insulin, we determined whether baseline homeostasis model assessment of insulin resistance (HOMA-IR; n = 4303) or the change in HOMA-IR on assigned study treatment (n = 3568) was related to the risk of death or major adverse cardiovascular events (cardiovascular death, myocardial infarction, and stroke) in unadjusted and adjusted models. Because an inverse association of HOMA-IR with N-terminal pro-B-type natriuretic peptide (NT-proBNP) has been described, we specifically examined effects of adjustment for the latter. Results: In unadjusted analysis, twofold higher baseline HOMA-IR was associated with lower risk of death [hazard ratio (HR): 0.79, 95% CI: 0.68 to 0.91, P = 0.002]. Adjustment for 24 standard demographic and clinical variables had minimal effect on this association. However, after further adjustment for NT-proBNP, the association of HOMA-IR with death was no longer present (adjusted HR: 0.99, 95% CI: 0.83 to 1.19, P = 0.94). Baseline HOMA-IR was not associated with major adverse cardiovascular events, nor was the change in HOMA-IR on study treatment associated with death or major adverse cardiovascular events. Conclusions: After accounting for levels of NT-proBNP, insulin resistance assessed by HOMA-IR is not related to the risk of death or major adverse cardiovascular events in patients with type 2 diabetes and ACS.