Background Medical Therapy and Clinical Outcomes From the VICTORIA Trial.

BACKGROUND: We examined whether the primary composite outcome (cardiovascular death or heart failure hospitalization) was related to differences in background use and dosing of guideline-directed medical therapy in patients with heart failure with reduced ejection fraction enrolled in VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction), a randomized trial of vericiguat versus placebo. METHODS: We evaluated the adherence to guideline use of angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, angiotensin receptor-neprilysin inhibitors, beta-blockers, and mineralocorticoid receptor antagonists. We assessed basic adherence; indication-corrected adherence accounting for guideline indications and contraindications; and dose-corrected adherence (indication-corrected adherence+≥50% of drug dose target). Associations between study treatment and the primary composite outcome according to the adherence to guidelines were assessed using multivariable adjustment; adjusted hazard ratios with 95% CIs and Pinteraction are reported. RESULTS: Of 5050 patients, 5040 (99.8%) had medication data at baseline. For angiotensin-converting enzyme inhibitor, angiotensin-receptor blockers, and angiotensin receptor-neprilysin inhibitors, basic adherence to guidelines was 87.4%, indication-corrected was 95.7%, and dose-corrected was 50.9%. For beta-blockers, basic adherence was 93.1%, indication-corrected was 96.2%, and dose-corrected was 45.4%. For mineralocorticoid receptor antagonists, basic adherence was 70.3%, indication-corrected was 87.1%, and dose-corrected was 82.2%. For triple therapy (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, or angiotensin receptor-neprilysin inhibitors+beta-blocker+mineralocorticoid receptor antagonist), basic adherence was 59.7%, indication-corrected was 83.3%, and dose-corrected was 25.5%. Using basic or dose-corrected adherence, the treatment effect of vericiguat was consistent across adherence to guidelines groups, with or without multivariable adjustment with no treatment heterogeneity. CONCLUSIONS: Patients in VICTORIA were well treated with heart failure with reduced ejection fraction medications. The efficacy of vericiguat was consistent across background therapy with very high adherence to guidelines accounting for patient-level indications, contraindications, and tolerance. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02861534.

Cannabinoids to Improve Health-Related Quality of Life in Patients with Neurological or Oncological Disease: A Meta-Analysis.

Background: Cannabinoids have been suggested to alleviate frequently experienced symptoms of reduced mental well-being such as anxiety and depression. Mental well-being is an important subdomain of health-related quality of life (HRQoL). Reducing symptoms and maintaining HRQoL are particularly important in malignant primary brain tumor patients, as treatment options are often noncurative and prognosis remains poor. These patients frequently report unprescribed cannabinoid use, presumably for symptom relieve. As studies on brain tumor patients specifically are lacking, we performed a meta-analysis of the current evidence on cannabinoid efficacy on HRQoL and mental well-being in oncological and neurological patients. Methods: We performed a systematic PubMed, PsychINFO, Embase, and Web of Science search according to PRISMA guidelines on August 2 and 3, 2021. We included randomized controlled trials (RCTs) that assessed the effects of tetrahydrocannabinol (THC) or cannabidiol (CBD) on general HRQoL and mental well-being. Pooled effect sizes were calculated using Hedges g. Risk of bias of included studies was assessed using Cochrane's Risk of Bias tool. Results: We included 17 studies: 4 in oncology and 13 in central nervous system (CNS) disease. Meta-analysis showed no effect of cannabinoids on general HRQoL (g=-0.02 confidence interval [95% CI -0.11 to 0.06]; p=0.57) or mental well-being (g=-0.02 [95% CI -0.16 to 0.13]; p=0.81). Conclusions: RCTs in patients with cancer or CNS disease showed no effect of cannabinoids on HRQoL or mental well-being. However, studies were clinically heterogeneous and since many glioma patients currently frequently use cannabinoids, future studies are necessary to evaluate its value in this specific population.

Vericiguat and NT-proBNP in patients with heart failure with reduced ejection fraction: analyses from the VICTORIA trial.

AIMS: Treatment response to vericiguat, based on baseline N-terminal pro-brain natriuretic peptide (NT-proBNP) subgroups specified in the protocol, was evaluated in the heart failure (HF) VICTORIA trial population by post hoc analysis of combined lower three quartiles [Q1-Q3] vs. the upper quartile [Q4]. METHODS AND RESULTS: VICTORIA participants with available baseline NT-proBNP levels (n = 4805; 95.1% of total) were included. Compared with patients in Q1-Q3 (NT-proBNP: Q1, ≤1556 pg/mL; Q2, >1556-2816 pg/mL; and Q3, >2816-5314 pg/mL), patients in Q4 (NT-proBNP: >5314 pg/mL) were older (69.2 ± 12.0 vs. 66.6 ± 12.1 years), had lower mean ejection fraction (27.2 ± 8.3% vs. 29.5 ± 8.2%; P < 0.0001), and were more likely to be in New York Heart Association (NYHA) Class III (51.8 vs. 35.6%) or IV (2.4 vs. 1.0%). Compared with Q1-Q3, patients in Q4 had higher mean Meta-Analysis Global Group in Chronic Heart Failure risk score (27.3 ± 6.6 vs. 23.5 ± 6.4; P < 0.0001), had lower mean estimated glomerular filtration rate (eGFR; 51.5 ± 25.5 vs. 65.0 ± 26.8 mL/min/1.73 m2 ; P < 0.0001) and haemoglobin (12.8 ± 2.0 vs. 13.6 ± 1.9 g/dL; P < 0.0001), and more had atrial fibrillation (48.7% vs. 43.1%; P = 0.0007) and were randomized while hospitalized for HF (14.8 vs. 9.9%; P < 0.0001). Target dose was achieved in 72.3 and 63.7% of patients in Q1-Q3 and Q4, respectively (P < 0.0001). Primary outcome (composite of time to cardiovascular death or first HF hospitalization) rates were 24.5 and 31.7 per 100 patient-years for vericiguat and placebo in Q1-Q3 [hazard ratio (HR) 0.78; 95% confidence interval (CI) 0.69-0.88, P < 0.001] and 73.6 and 63.6 in Q4 (HR 1.15; 95% CI 0.99-1.34, P = 0.070). Serious adverse events were more frequent in NT-proBNP Q4 (total population) compared with Q1-Q3 (38.3 vs. 32.3%; P = 0.0001), driven mainly by the placebo group. Adverse events leading to death were more frequent in Q4 than Q1-Q3 (5.8 vs. 2.4%; P < 0.0001). CONCLUSIONS: Plasma NT-proBNP may help identify patients with worsening HF with reduced ejection fraction, in whom the beneficial effects of vericiguat may be highest. Patients with highest NT-proBNP values are probably too far advanced, suffering more co-morbidities, or still clinically unstable after decompensation to derive benefit from vericiguat.

Effect of P2Y12 Inhibitors on Survival Free of Organ Support Among Non-Critically Ill Hospitalized Patients With COVID-19: A Randomized Clinical Trial.

Importance: Platelets represent a potential therapeutic target for improved clinical outcomes in patients with COVID-19. Objective: To evaluate the benefits and risks of adding a P2Y12 inhibitor to anticoagulant therapy among non-critically ill patients hospitalized for COVID-19. Design, Setting, and Participants: An open-label, bayesian, adaptive randomized clinical trial including 562 non-critically ill patients hospitalized for COVID-19 was conducted between February 2021 and June 2021 at 60 hospitals in Brazil, Italy, Spain, and the US. The date of final 90-day follow-up was September 15, 2021. Interventions: Patients were randomized to a therapeutic dose of heparin plus a P2Y12 inhibitor (n = 293) or a therapeutic dose of heparin only (usual care) (n = 269) in a 1:1 ratio for 14 days or until hospital discharge, whichever was sooner. Ticagrelor was the preferred P2Y12 inhibitor. Main Outcomes and Measures: The composite primary outcome was organ support-free days evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and, for those who survived to hospital discharge, the number of days free of respiratory or cardiovascular organ support up to day 21 of the index hospitalization (range, -1 to 21 days; higher scores indicate less organ support and better outcomes). The primary safety outcome was major bleeding by 28 days as defined by the International Society on Thrombosis and Hemostasis. Results: Enrollment of non-critically ill patients was discontinued when the prespecified criterion for futility was met. All 562 patients who were randomized (mean age, 52.7 [SD, 13.5] years; 41.5% women) completed the trial and 87% received a therapeutic dose of heparin by the end of study day 1. In the P2Y12 inhibitor group, ticagrelor was used in 63% of patients and clopidogrel in 37%. The median number of organ support-free days was 21 days (IQR, 20-21 days) among patients in the P2Y12 inhibitor group and was 21 days (IQR, 21-21 days) in the usual care group (adjusted odds ratio, 0.83 [95% credible interval, 0.55-1.25]; posterior probability of futility [defined as an odds ratio <1.2], 96%). Major bleeding occurred in 6 patients (2.0%) in the P2Y12 inhibitor group and in 2 patients (0.7%) in the usual care group (adjusted odds ratio, 3.31 [95% CI, 0.64-17.2]; P = .15). Conclusions and Relevance: Among non-critically ill patients hospitalized for COVID-19, the use of a P2Y12 inhibitor in addition to a therapeutic dose of heparin, compared with a therapeutic dose of heparin only, did not result in an increased odds of improvement in organ support-free days within 21 days during hospitalization. Trial Registration: ClinicalTrials.gov Identifier: NCT04505774.

Cardiovascular risk factors during cancer treatment. Prevalence and prognostic relevance: insights from the CARDIOTOX registry.

AIMS: The actual usefulness of cardiovascular (CV) risk factor assessment in the prognostic evaluation of cancer patients treated with cardiotoxic treatment remains largely unknown. Prospective multicentre study in patients scheduled to receive anticancer therapy related with moderate/high cardiotoxic risk. METHODS AND RESULTS: A total of 1324 patients underwent follow-up in a dedicated cardio-oncology clinic from April 2012 to October 2017. Special care was given to the identification and control of CV risk factors. Clinical data, blood samples, and echocardiographic parameters were prospectively collected according to protocol, at baseline before cancer therapy and then at 3 weeks, 3 months, 6 months, 1 year, 1.5 years, and 2 years after initiation of cancer therapy. At baseline, 893 patients (67.4%) presented at least one risk factor, with a significant number of patients newly diagnosed during follow-up. Individual risk factors were not related with worse prognosis during a 2-year follow-up. However, a higher Systemic Coronary Risk Estimation (SCORE) was significantly associated with higher rates of severe cardiotoxicity (CTox) and all-cause mortality [hazard ratio (HR) 1.79 (95% confidence interval, CI 1.16-2.76) for SCORE 5-9 and HR 4.90 (95% CI 2.44-9.82) for SCORE ≥10 when compared with patients with lower SCORE (0-4)]. CONCLUSIONS: This large cohort of patients treated with a potentially cardiotoxic regimen showed a significant prevalence of CV risk factors at baseline and significant incidence during follow-up. Baseline CV risk assessment using SCORE predicted severe CTox and all-cause mortality. Therefore, its use should be considered in the evaluation of cancer patients.

Causes of Cardiovascular Hospitalization and Death in Patients With Transthyretin Amyloid Cardiomyopathy (from the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial [ATTR-ACT]).

In the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT), tafamidis significantly reduced mortality and cardiovascular (CV)-related hospitalizations compared with placebo in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). This analysis aimed to assess the causes of CV-related death and hospitalization in ATTR-ACT to provide further insight into the progression of ATTR-CM and efficacy of tafamidis. ATTR-ACT was an international, double-blind, placebo-controlled, and randomized study. Patients with hereditary or wild-type ATTR-CM were randomized to tafamidis (n = 264) or placebo (n = 177) for 30 months. The independent Endpoint Adjudication Committee determined whether certain investigator-reported events met the definition of disease-related efficacy endpoints using predefined criteria. Cause-specific reasons for CV-related deaths (heart failure [HF], arrhythmia, myocardial infarction, sudden death, stroke, and other CV causes) and hospitalizations (HF, arrhythmia, myocardial infarction, transient ischemic attack/stroke, and other CV causes) were assessed. Total CV-related deaths was 53 (20.1%) with tafamidis and 50 (28.2%) with placebo, with HF (15.5% tafamidis, 22.6% placebo), followed by sudden death (2.7% tafamidis, 5.1% placebo), the most common causes. The number of patients with a CV-related hospitalization was 138 (52.3%) with tafamidis and 107 (60.5%) with placebo; with HF the most common cause (43.2% tafamidis, 50.3% placebo). All predefined causes of CV-related death or hospitalization were less frequent with tafamidis than placebo. In conclusion, these data provide further insight into CV disease progression in patients with ATTR-CM, with HF the most common adjudicated cause of CV-related hospitalization or death in ATTR-ACT. Clinical trial registration ClinicalTrials.gov: NCT01994889.

Association of Different Estimates of Renal Function With Cardiovascular Mortality and Bleeding in Atrial Fibrillation.

Background We compared different methods of estimated glomerular filtration rate (eGFR) and their association with cardiovascular death and major bleeding in 14 980 patients with atrial fibrillation in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. Methods and Results eGFR was calculated using equations based on creatinine (Cockcroft-Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) and/or cystatin C (CKD-EPICysC and CKD-EPICysC+Creatinine). These 5 eGFR equations, as well as the individual variables that are used in these equations, were assessed for correlation and discriminatory ability for cardiovascular death and major bleeding. The median age was 70.0 years, and 35.6% were women. The median eGFR was highest with Cockcroft-Gault (74.1 mL/min) and CKD-EPICysC (74.2 mL/min), and lowest with Modification of Diet in Renal Disease (66.5 mL/min). Correlation between methods ranged from 0.49 (Cockroft-Gault and CKD-EPICysC) to 0.99 (Modification of Diet in Renal Disease and CKD-EPI). Among the eGFR equations, those based on cystatin C yielded the highest C indices for cardiovascular death and major bleeding: 0.628 (CKD-EPICysC) and 0.612 (CKD-EPICysC+Creatinine), respectively. A model based on the variables within the different eGFR equations (age, sex, weight, creatinine, and cystatin C) yielded the highest discriminatory value for both outcomes, with a C index of 0.673 and 0.656, respectively. Conclusions In patients with atrial fibrillation on anticoagulation, correlation between eGFR calculated using different methods varied substantially. Cystatin C-based eGFRs seem to provide the most robust information for predicting death and bleeding. A model based on the individual variables within the eGFR equations, however, provided the highest discriminatory value. Our findings may help refine risk stratification in patients with atrial fibrillation and define how renal function should be determined in future atrial fibrillation studies. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT00412984.

Comparison of Dabigatran Plus a P2Y12 Inhibitor With Warfarin-Based Triple Therapy Across Body Mass Index in RE-DUAL PCI.

BACKGROUND: Body mass index (BMI) affects drug levels of nonvitamin K antagonist oral anticoagulants. We sought to assess whether BMI affected outcomes in the RE-DUAL PCI trial. METHODS: RE-DUAL PCI (NCT02164864) evaluated the safety and efficacy of a dual-antithrombotic-therapy regimen using dabigatran (110 mg or 150 mg twice daily and a P2Y12 platelet antagonist) in comparison with triple therapy of warfarin, aspirin, and a P2Y12 platelet inhibitor in 2725 patients with atrial fibrillation who had undergone percutaneous coronary intervention (PCI). We compared the risk of first International Society on Thrombosis and Haemostasis (ISTH)-defined major or clinically relevant nonmajor bleeding events (primary endpoint) and the composite of death, myocardial infarction, stroke, systemic embolism, or unplanned revascularization (main efficacy endpoint) in relation to baseline BMI. RESULTS: Median (range) BMI was 28.1 (14-66) kg/m2. Dabigatran dual therapy versus warfarin triple therapy had relevantly and similarly lower rates of bleeding at both 110 mg and 150 mg twice-daily doses, irrespective of BMI. Thromboembolic event rates appeared consistent across categories of BMI, including those <25 and ≥35 kg/m2 (P for interaction: 0.806 and 0.279, respectively). CONCLUSIONS: The reduction in bleeding with dabigatran dual therapy compared with warfarin triple therapy in patients here evaluated appears consistent across BMI categories.

Initial Invasive or Conservative Strategy for Stable Coronary Disease.

BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).

Effectiveness of sacubitril-valsartan in cancer patients with heart failure.

AIMS: Current guidelines recommend sacubitril/valsartan for patients with heart failure and reduced left ventricular ejection fraction (LVEF), but there is lack of evidence of its efficacy and safety in cancer therapy-related cardiac dysfunction (CTRCD). Our aim was to analyse the potential benefit of sacubitril/valsartan in patients with CTRCD. METHODS AND RESULTS: We performed a retrospective multicentre registry (HF-COH) in six Spanish hospitals with cardio-oncology clinics including all patients treated with sacubitril/valsartan. Demographic and clinical characteristics and laboratory and echocardiographic data were collected. Median follow-up was 4.6 [1; 11] months. Sixty-seven patients were included (median age was 63 ± 14 years; 64% were female, 87% had at least one cardiovascular risk factor). Median time from anti-cancer therapy to CTRD was 41 [10; 141] months. Breast cancer (45%) and lymphoma (39%) were the most frequent neoplasm, 31% had metastatic disease, and all patients were treated with combination antitumor therapy (70% with anthracyclines). Thirty-nine per cent of patients had received thoracic radiotherapy. Baseline median LVEF was 33 [27; 37], and 21% had atrial fibrillation. Eighty-five per cent were on beta-blocker therapy and 76% on mineralocorticoid receptor antagonists; 90% of the patients were symptomatic NYHA functional class ≥II. Maximal sacubitril/valsartan titration dose was achieved in 8% of patients (50 mg b.i.d.: 60%; 100 mg b.i.d.: 32%). Sacubitril/valsartan was discontinued in four patients (6%). Baseline N-terminal pro-B-type natriuretic peptide levels (1552 pg/mL [692; 3624] vs. 776 [339; 1458]), functional class (2.2 ± 0.6 vs. 1.6 ± 0.6), and LVEF (33% [27; 37] vs. 42 [35; 50]) improved at the end of follow-up (all P values ≤0.01). No significant statistical differences were found in creatinine (0.9 mg/dL [0.7; 1.1] vs. 0.9 [0.7; 1.1]; P = 0.055) or potassium serum levels (4.5 mg/dL [4.1; 4.8] vs. 4.5 [4.2; 4.8]; P = 0.5). Clinical, echocardiographic, and biochemical improvements were found regardless of the achieved sacubitril-valsartan dose (low or medium/high doses). CONCLUSIONS: Our experience suggests that sacubitril/valsartan is well tolerated and improves echocardiographic functional and structural parameters, N-terminal pro-B-type natriuretic peptide levels, and symptomatic status in patients with CTRCD.

Classification, prevalence, and outcomes of anticancer therapy-induced cardiotoxicity: the CARDIOTOX registry.

AIM: Cardiotoxicity (CTox) is a major side effect of cancer therapies, but uniform diagnostic criteria to guide clinical and research practices are lacking. METHODS AND RESULTS: We prospectively studied 865 patients, aged 54.7 ± 13.9; 16.3% men, scheduled for anticancer therapy related with moderate/high CTox risk. Four groups of progressive myocardial damage/dysfunction were considered according to current guidelines: normal, normal biomarkers (high-sensitivity troponin T and N-terminal natriuretic pro-peptide), and left ventricular (LV) function; mild, abnormal biomarkers, and/or LV dysfunction (LVD) maintaining an LV ejection fraction (LVEF) ≥50%; moderate, LVD with LVEF 40-49%; and severe, LVD with LVEF ≤40% or symptomatic heart failure. Cardiotoxicity was defined as new or worsening of myocardial damage/ventricular function from baseline during follow-up. Patients were followed for a median of 24 months. Cardiotoxicity was identified in 37.5% patients during follow-up [95% confidence interval (CI) 34.22-40.8%], 31.6% with mild, 2.8% moderate, and 3.1% with severe myocardial damage/dysfunction. The mortality rate in the severe CTox group was 22.9 deaths per 100 patients-year vs. 2.3 deaths per 100 patients-year in the rest of groups, hazard ratio of 10.2 (95% CI 5.5-19.2) (P < 0.001). CONCLUSIONS: The majority of patients present objective data of myocardial injury/dysfunction during or after cancer therapy. Nevertheless, severe CTox, with a strong prognostic relationship, was comparatively rare. This should be reflected in protocols for clinical and research practices.

Feasibility and safety of pulmonary vein isolation by high-power short-duration radiofrequency application: short-term results of the POWER-FAST PILOT study.

PURPOSE: Pulmonary vein (PV) isolation (PVI) by point-by-point radiofrequency application (PPRF) results in longer procedures than that achieved by single-shot ablation techniques. In addition, it is associated with significant risk of oesophageal injury. The POWER-FAST pilot study evaluated the feasibility and safety of PVI by high-power short-duration (HPSD) PPRF. METHODS: HPSD PPRF around the PVs was done in 48 consecutive patients with atrial fibrillation. Fifty watts was delivered until a predefined lesion index value was reached (LSI ≥ 5 or Abl-I ≥ 350) and 60 W during 7-10 s in the first 18 and last 30 patients, respectively. A control group of 47 consecutive patients who had undergone PVI before the HPSD group with conventional PPRF (30 W for 30 s) was included for reference. Echocardiography and oesophageal endoscopy was performed shortly after ablation in all patients. RESULTS: PVI of all targeted veins was achieved in 98% and 100% of patients of the conventional and HPSD groups, respectively (p = 0.59). Total radiofrequency time was 34 ± 11, 24 ± 8, and 15 ± 5 min in groups 30 W, 50 W, and 60 W (p < 0.001). Audible steam pops occurred in 4 out of 48 (8%) patients in the HPSD group, accounting for 4 (0.08%) out of 5 269 HPSD radiofrequency applications. No patient in the HPSD group developed pericardial effusion. The incidence of oesophageal lesions was 28%, 22%, and 0% in groups 30 W, 50 W, and 60 W, respectively (p = 0.007) CONCLUSIONS: PVI can be achieved with HPSD PPRF in most patients. This approach appears safe and associated with low risk of esophageal damage.

Long term clinical outcomes in survivors after out-of-hospital cardiac arrest.

INTRODUCTION AND OBJECTIVES: Information regarding long-term outcomes in patients surviving out-of-hospital cardiac arrest (OHCA) is scarce. Our aim was to study the long-term clinical outcomes of a large cohort of OHCA patients surviving until hospital discharge and to identify predictors of mortality and cardiovascular events. METHODS: Consecutive OHCA patients admitted in the Acute Cardiac Care Unit who survived at least until hospital discharge between 2007 and 2019 were included. All received therapeutic hypothermia according to the local protocol. Pre- and intra-hospital clinical and analytical variables were analyzed, as well as the clinically relevant events during follow-up. RESULTS: A total of 201 patients were included, with a mean age of 57.6 ± 14.2 years, 168 (83.6%) were male. Thirty-six (17.9%) died during a median follow-up of 40.3 months (18.9-69.1), the most frequent causes of death being cardiovascular and neurological, followed by cancer. We calculated a predictive model for mortality during follow-up using Cox regression that included the following variables: poor neurological outcome [HR 3.503 (1.578-7.777)], non-shockable rhythm [HR 2.926 (1.390-6.163)], time to onset of CPR [HR 1.063 (0.997-1.134)], older age [1.036 (1.008-1.064)) and worse ejection fraction at discharge [1.033 (1.009-1.058)]. CONCLUSIONS: Even though few patients experience recurrent cardiac arrest events, survivors after OHCA face high morbidity and mortality during long-term follow-up. Therefore, they may benefit from multidisciplinary teams providing an integral management and ensuring continuity of care.

Complete Revascularization with Multivessel PCI for Myocardial Infarction.

BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI), percutaneous coronary intervention (PCI) of the culprit lesion reduces the risk of cardiovascular death or myocardial infarction. Whether PCI of nonculprit lesions further reduces the risk of such events is unclear. METHODS: We randomly assigned patients with STEMI and multivessel coronary artery disease who had undergone successful culprit-lesion PCI to a strategy of either complete revascularization with PCI of angiographically significant nonculprit lesions or no further revascularization. Randomization was stratified according to the intended timing of nonculprit-lesion PCI (either during or after the index hospitalization). The first coprimary outcome was the composite of cardiovascular death or myocardial infarction; the second coprimary outcome was the composite of cardiovascular death, myocardial infarction, or ischemia-driven revascularization. RESULTS: At a median follow-up of 3 years, the first coprimary outcome had occurred in 158 of the 2016 patients (7.8%) in the complete-revascularization group as compared with 213 of the 2025 patients (10.5%) in the culprit-lesion-only PCI group (hazard ratio, 0.74; 95% confidence interval [CI], 0.60 to 0.91; P = 0.004). The second coprimary outcome had occurred in 179 patients (8.9%) in the complete-revascularization group as compared with 339 patients (16.7%) in the culprit-lesion-only PCI group (hazard ratio, 0.51; 95% CI, 0.43 to 0.61; P<0.001). For both coprimary outcomes, the benefit of complete revascularization was consistently observed regardless of the intended timing of nonculprit-lesion PCI (P = 0.62 and P = 0.27 for interaction for the first and second coprimary outcomes, respectively). CONCLUSIONS: Among patients with STEMI and multivessel coronary artery disease, complete revascularization was superior to culprit-lesion-only PCI in reducing the risk of cardiovascular death or myocardial infarction, as well as the risk of cardiovascular death, myocardial infarction, or ischemia-driven revascularization. (Funded by the Canadian Institutes of Health Research and others; COMPLETE ClinicalTrials.gov number, NCT01740479.).

Efficacy and safety with ticagrelor in patients with prior myocardial infarction in the approved European label: insights from PEGASUS-TIMI 54.

AIMS: In PEGASUS-TIMI 54, ticagrelor significantly reduced the risk of the composite of major adverse cardiovascular (CV) events by 15-16% in stable patients with a prior myocardial infarction (MI) 1-3 years earlier. We report the efficacy and safety in the subpopulation recommended for treatment in the European (EU) label, i.e. treatment with 60 mg b.i.d. initiated up to 2 years from the MI, or within 1 year after stopping previous adenosine diphosphate receptor inhibitor treatment. METHODS AND RESULTS: Of the 21 162 patients enrolled in PEGASUS-TIMI 54, 10 779 patients were included in the primary analysis for this study, randomized to ticagrelor 60 mg (n = 5388) or matching placebo (n = 5391). The cumulative proportions of patients with events at 36 months were calculated by the Kaplan-Meier (KM) method. The composite of CV death, MI, or stroke occurred less frequently in the ticagrelor group (7.9% KM rate vs. 9.6%), hazard ratio (HR) 0.80 [95% confidence interval (CI) 0.70-0.91; P = 0.001]. Ticagrelor also reduced the risk of all-cause mortality, HR 0.80 (0.67-0.96; P = 0.018). Thrombolysis in myocardial infarction major bleeding was more frequent in the ticagrelor group 2.5% vs. 1.1%; HR 2.36 (1.65-3.39; P < 0.001). The corresponding HR for fatal or intracranial bleeding was 1.17 (0.68-2.01; P = 0.58). CONCLUSION: In PEGASUS-TIMI 54, treatment with ticagrelor 60 mg as recommended in the EU label, was associated with a relative risk reduction of 20% in CV death, MI, or stroke. Thrombolysis in myocardial infarction major bleeding was increased, but fatal or intracranial bleeding was similar to placebo. There appears to be a favourable benefit-risk ratio for long-term ticagrelor 60 mg in this population. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov NCT01225562.

Percutaneous balloon pericardiotomy: Treatment of choice in patients with advanced oncological disease and severe pericardial effusion.

INTRODUCTION AND OBJECTIVES: Malignant pericardial effusion has a high recurrence rate after pericardiocentesis. We sought to confirm the efficacy and feasibility of percutaneous balloon pericardiotomy (PBP) as the initial treatment of choice for these effusions. METHODS: Retrospective analysis of the clinical, echocardiographic, and follow-up characteristics of a consecutive series of PBP carried out in a single-center in patients with advanced cancer. RESULTS: Forty PBPs were performed in 35 patients with a mean age of 61.8years (55% females). Thirty-four patients had pathologically confirmed metastatic neoplastic disease (26 patients with tumoral cells in the pericardial liquid), 7 had previously required pericardiocentesis, and in the remaining patients PBP was the first treatment for the effusion. All patients had a severe circumferential effusion (29mm by mean on transthoracic echocardiography [TTE]), and most presented evidence of hemodynamic compromise on TTE. In all cases, the procedure was successful, there were no acute complications, and it was well tolerated at the first attempt. There were no infectious complications during follow-up. One patient developed a pseudoaneurysm in the right ventricle, even though no further treatment was required. Eight patients needed a new pericardial procedure: 3 had elective pericardial window surgeries and 5 had a second PBP. Eighty percent of patients died during follow-up (57days by mean from the PBP) regarding their oncological disease. CONCLUSION: PBP is a simple and safe technique that can be effective in the prevention of recurrence in many patients with severe malignant pericardial effusion. The characteristics of this procedure make it particularly useful in this group of patients to avoid more aggressive, poorly tolerated approaches, since they have a very poor prognosis regarding to their oncological disease.