Consensus on the approach to hydrosaline overload in acute heart failure. SEMI/SEC/S.E.N. recommendations.

Most of the signs and symptoms of heart failure can be explained by fluid overload, which is also related to disease progression. Fluid overload is a complex phenomenon that extends beyond increased intravascular pressures and poses challenges for accurate diagnosis and effective treatment. Current recommendations advise a multiparametric approach, including clinical data (symptoms/signs), imaging tests, and biomarkers. This article proposes a practical therapeutic approach to managing hydrosaline overload in heart failure in both inpatient and outpatient settings. This document is an initiative of the Spanish Society of Internal Medicine (SEMI) in collaboration with the Spanish Society of Cardiology (SEC) and the Spanish Society of Nephrology (S.E.N.).

Heart failure in older patients with atrial fibrillation: incidence and risk factors.

INTRODUCTION AND OBJECTIVES: Atrial fibrillation (AF) is linked to heart failure (HF). However, little has been published on the factors that may precipitate the onset of HF in AF patients. We aimed to determine the incidence, predictors, and prognosis of incident HF in older patients with AF with no prior history of HF. METHODS: Patients with AF older than 80 years and without prior HF were identified between 2014 and 2018. RESULTS: A total of 5794 patients (mean age, 85.2±3.8 years; 63.2% women) were followed up for 3.7 years. Incident HF, predominantly with preserved left ventricular ejection fraction, developed in 33.3% (incidence rate, 11.5-100 people-year). Multivariate analysis identified 11 clinical risk factors for incident HF, irrespective of HF subtype: significant valvular heart disease (HR, 1.99; 95%CI, 1.73-2.28), reduced baseline left ventricular ejection fraction (HR, 1.92; 95%CI, 1.68-2.19), chronic pulmonary obstructive disease (HR, 1.59; 95%CI, 1.40-1.82), enlarged left atrium (HR 1.47, 95%CI 1.33-1.62), renal dysfunction (HR 1.36, 95%CI 1.24-1.49), malnutrition (HR, 1.33; 95%CI, 1.21-1.46), anemia (HR, 1.30; 95%CI, 1.17-1.44), permanent AF (HR, 1.15; 95%CI, 1.03-1.28), diabetes mellitus (HR, 1.13; 95%CI, 1.01-1.27), age per year (HR, 1.04; 95%CI, 1.02-1.05), and high body mass index for each kg/m2 (HR, 1.03; 95%CI, 1.02-1.04). The presence of incident HF nearly doubled the mortality risk (HR, 1.67; 95%CI, 1.53-1.81). CONCLUSIONS: The presence of HF in this cohort was relatively frequent and nearly doubled the mortality risk. Eleven risk factors for HF were identified, expanding the scope for primary prevention among elderly patients with AF.

Forecasting the Risk of Heart Failure Hospitalization After Acute Coronary Syndromes: the CORALYS HF Score.

The present study aimed to identify patients at a higher risk of hospitalization for heart failure (HF) in a population of patients with acute coronary syndrome (ACS) treated with percutaneous coronary revascularization without a history of HF or reduced left ventricular (LV) ejection fraction before the index admission. We performed a Cox regression multivariable analysis with competitive risk and machine learning models on the incideNce and predictOrs of heaRt fAiLure After Acute coronarY Syndrome (CORALYS) registry (NCT04895176), an international and multicenter study including consecutive patients admitted for ACS in 16 European Centers from 2015 to 2020. Of 14,699 patients, 593 (4.0%) were admitted for the development of HF up to 1 year after the index ACS presentation. A total of 2 different data sets were randomly created, 1 for the derivative cohort including 11,626 patients (80%) and 1 for the validation cohort including 3,073 patients (20%). On the Cox regression multivariable analysis, several variables were associated with the risk of HF hospitalization, with reduced renal function, complete revascularization, and LV ejection fraction as the most relevant ones. The area under the curve at 1 year was 0.75 (0.72 to 0.78) in the derivative cohort, whereas on validation, it was 0.72 (0.67 to 0.77). The machine learning analysis showed a slightly inferior performance. In conclusion, in a large cohort of patients with ACS without a history of HF or LV dysfunction before the index event, the CORALYS HF score identified patients at a higher risk of hospitalization for HF using variables easily accessible at discharge. Further approaches to tackle HF development in this high-risk subset of patients are needed.

Impact of Complete Revascularization on Development of Heart Failure in Patients With Acute Coronary Syndrome and Multivessel Disease: A Subanalysis of the CORALYS Registry.

Background The impact of complete revascularization (CR) on the development of heart failure (HF) in patients with acute coronary syndrome and multivessel coronary artery disease undergoing percutaneous coronary intervention remains to be elucidated. Methods and Results Consecutive patients with acute coronary syndrome with multivessel coronary artery disease from the CORALYS (Incidence and Predictors of Heart Failure After Acute Coronary Syndrome) registry were included. Incidence of first hospitalization for HF or cardiovascular death was the primary end point. Patients were stratified according to completeness of coronary revascularization. Of 14 699 patients in the CORALYS registry, 5054 presented with multivessel disease. One thousand four hundred seventy-three (29.2%) underwent CR, while 3581 (70.8%) did not. Over 5 years follow-up, CR was associated with a reduced incidence of the primary end point (adjusted hazard ratio [HR], 0.66 [95% CI, 0.51-0.85]), first HF hospitalization (adjusted HR, 0.67 [95% CI, 0.49-0.90]) along with all-cause death and cardiovascular death alone (adjusted HR, 0.74 [95% CI, 0.56-0.97] and HR, 0.56 [95% CI, 0.38-0.84], respectively). The results were consistent in the propensity-score matching population and in inverse probability treatment weighting analysis. The benefit of CR was consistent across acute coronary syndrome presentations (HR, 0.59 [95% CI, 0.39-0.89] for ST-segment elevation myocardial infarction and HR, 0.71 [95% CI, 0.50-0.99] for non-ST-elevation acute coronary syndrome) and in patients with left ventricular ejection fraction >40% (HR, 0.52 [95% CI, 0.37-0.72]), while no benefit was observed in patients with left ventricular ejection fraction ≤40% (HR, 0.77 [95% CI, 0.37-1.10], P for interaction 0.04). Conclusions CR after acute coronary syndrome reduced the risk of first hospitalization for HF and cardiovascular death, as well as first HF hospitalization, and cardiovascular and overall death both in patients with ST-segment elevation myocardial infarction and non-ST-elevation acute coronary syndrome. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04895176.

Hypotension at heart failure discharge: Should it be a limiting factor for drug titration?

BACKGROUND: Medical treatment in Heart Failure (HF) with reduced ejection fraction (HFrEF; LVEF ≤40%) has shifted towards quadruple therapy. Maximum tolerated dose is the goal, yet no hypotension's cut-off point has been specified. In this work, we analyze the impact of intensive drug titration in clinical events, focusing on low blood pressure (BP) patients at hospital discharge. METHODS AND RESULTS: Retrospective analysis of 713 patients with HFrEF discharged after an acute HF event (mean LVEF 30 ± 5%). Mean SBP was 112.4 ± 16.5 mmHg and 50.6% were discharged on triple therapy. We considered hypotension as a Systolic blood pressure (SBP) <100 mmHg (21.7% of patients, mean SBP was 112.4 ± 16.5 mmHg) and codified the intensity of drug therapy in 5 stages from untreated to very high therapy intensity. The impact of the intensity of treatment was analysed with a propensity score and increasing the intensity was associated in the whole cohort with a reduction of the composite outcome of all-cause mortality and HF readmission, (HR 0.69; CI95% 0.57-0.85, p < 0.001) and benefit in mortality was maintained for SBP < 100 mmHg (HR 0.42; CI95% 0.22-0.82; p = 0.011). Moreover, therapy intensity was clearly associated with lower risk of HF-hospitalization and death after the additional regression, considering SBP as a covariate, in the whole cohort (HR 0.70; CI95% 0.57-0.85; p < 0.001). CONCLUSIONS: In this retrospective cohort analysis, patients with HFrEF and an acute-HF admission, intensive drug dose titration was related to better outcomes, even in patients with low blood pressure at hospital discharge. Therefore, hypotension is not a contraindication for NHB uptitration.

Left Ventricular Assist Device as a Destination Therapy: Current Situation and the Importance of Patient Selection.

Advanced heart failure is a growing problem for which the best treatment is cardiac transplantation. However, the shortage of donors' hearts made left ventricular assist devices as destination therapy (DT-LVAD) a highly recommended alternative: they improved mid-term prognosis as well as patients' quality of life. Current intracorporeal pumps with a centrifugal continuous flow evolved in the last few years. Since 2003, when first LVAD was approved for long-term support, smaller device sizes with better survival and hemocompatibility profile were reached. The most important difficulty lies in the moment of the implant. Recent indications range from INTERMACS class 2 to 4, with close monitoring in intermediate cases. Moreover, a large multiparametric study is needed for considering the candidacy: basal situation, with a special interest in frailty, comorbidities, including renal and hepatic dysfunction, and medical background, considering every prior cardiac condition, must be evaluated. In addition, some clinical risk scores can be helpful to measure the possibility of right heart failure or morbi-mortality. With this review, we sought to summarize all the device improvements, with their updated clinical results, as well as to focus on all the patient selection criteria.

Effectiveness and Safety of Balloon Pulmonary Angioplasty for the Treatment of Patients with Persistent Pulmonary Hypertension after Pulmonary Endarterectomy.

(1) Background: Pulmonary endarterectomy (PEA) is the "gold standard" treatment for operable patients with chronic thromboembolic pulmonary hypertension (CTEPH). Persistent pulmonary hypertension (PH) after PEA confers a worse prognosis. Balloon pulmonary angioplasty (BPA) could represent a useful therapy in this setting, but evidence about its effectiveness and safety in patients with previous PEA is limited. (2) Methods: A total of 14 patients with persistent PH after PEA were treated with BPA in a single PH center. Hemodynamic and clinical effects of BPA and complications of the procedure were retrospectively collected. (3) Results: After BPA, the mean pulmonary arterial pressure fell from 50.7 ± 15.3 mmHg to 38.0 ± 7.9 mmHg (25.0% decrease; 95% confidence interval (CI) 14.0-35.5%; p = 0.01). Pulmonary vascular resistances were reduced from 8.5 ± 3.6 WU to 5.3 ± 2.2 WU (37.6% decrease; 95% CI 18.8-56.5%; p = 0.01). WHO functional class was also improved with BPA. Severe BPA-related complications were infrequent and no periprocedural deaths were observed. (4) Conclusions: BPA is an effective and safe therapy for patients with CTEPH and persistent PH after PEA.

Intermittent inotropic support with levosimendan in advanced heart failure as destination therapy: The LEVO-D registry.

AIM: Patients with advanced heart failure (AHF) who are not candidates to advanced therapies have poor prognosis. Some trials have shown that intermittent levosimendan can reduce HF hospitalizations in AHF in the short term. In this real-life registry, we describe the patterns of use, safety and factors related to the response to intermittent levosimendan infusions in AHF patients not candidates to advanced therapies. METHODS AND RESULTS: Multicentre retrospective study of patients diagnosed with advanced heart failure, not HT or LVAD candidates. Patients needed to be on the optimal medical therapy according to their treating physician. Patients with de novo heart failure or who underwent any procedure that could improve prognosis were not included in the registry. Four hundred three patients were included; 77.9% needed at least one admission the year before levosimendan was first administered because of heart failure. Death rate at 1 year was 26.8% and median survival was 24.7 [95% CI: 20.4-26.9] months, and 43.7% of patients fulfilled the criteria for being considered a responder lo levosimendan (no death, heart failure admission or unplanned HF visit at 1 year after first levosimendan administration). Compared with the year before there was a significant reduction in HF admissions (38.7% vs. 77.9%; P < 0.0001), unplanned HF visits (22.7% vs. 43.7%; P < 0.0001) or the combined event including deaths (56.3% vs. 81.4%; P < 0.0001) during the year after. We created a score that helps predicting the responder status at 1 year after levosimendan, resulting in a score summatory of five variables: TEER (+2), treatment with beta-blockers (+1.5), Haemoglobin >12 g/dL (+1.5), amiodarone use (-1.5) HF visit 1 year before levosimendan (-1.5) and heart rate >70 b.p.m. (-2). Patients with a score less than -1 had a very low probability of response (21.5% free of death or HF event at 1 year) meanwhile those with a score over 1.5 had the better chance of response (68.4% free of death or HF event at 1 year). LEVO-D score performed well in the ROC analysis. CONCLUSION: In this large real-life series of AHF patients treated with levosimendan as destination therapy, we show a significant decrease of heart failure events during the year after the first administration. The simple LEVO-D Score could be of help when deciding about futile therapy in this population.

A systematic review and meta-analysis of randomized controlled trials evaluating pharmacologic therapies for acute and recurrent pericarditis.

Acute idiopathic pericarditis (AIP) is a benign inflammatory condition associated with high recurrence rates. Non-steroidal anti-inflammatory drug (NSAIDs) and colchicine are the recommended therapies. Our objective was to systematically assess effects of pharmacological therapies on recurrences or treatment failure in patients with first and subsequent AIP episodes. PubMed, BioMedCentral, Cochrane, Clinicaltrials.gov, Google Scholar and EMBASE (Ovid) were searched up to April 2020 for randomized controlled trials (RCT) evaluating NSAIDs, indomethacin, colchicine, steroids, intravenous immunoglobulins, immunomodulators, or interleukin receptor antagonists in adult patients with acute episode of idiopathic pericarditis. Mantel-Haenzel random effects models were used for meta-analyses, and effects were reported as odds ratios (ORs) and their 95% confidence intervals (CI). Six RCTs of colchicine plus NSAIDs (n=914 patients) and one RCT of anakinra (n=21) were found. No RCTs testing NSAIDs or corticosteroids were identified. Colchicine plus NSAIDs and anakinra significantly reduced recurrence (OR 0.37; 95%CI 0.27-0.51; and OR 0.02; 95%CI, 0.00-0.32, respectively). Colchicine plus NSAIDs also reduced treatment failure (OR 0.29; 95%CI 0.21-0.41). No differences in adverse events between colchicine and placebo were found (OR 1.16; 95%CI 0.72 to 1.86). In conclusion, Colchicine plus NSAIDS and anakinra are efficacious for preventing AIP recurrences. Colchicine reduces treatment failure as well. Although its use is supported by clinical experience, no solid evidence is currently available for the role of NSAIDs or steroids in the treatment of AIP.

IncidenCe and predictOrs of heaRt fAiLure after acute coronarY Syndrome: The CORALYS registry.

BACKGROUND: Previous studies investigating predictors of Heart Failure (HF) after acute coronary syndrome (ACS) were mostly conducted during fibrinolytic era or restricted to baseline characteristics and diagnoses prior to admission. We assessed the incidence and predictors of HF hospitalizations among patients treated with percutaneous coronary intervention (PCI) for ACS. METHODS AND RESULTS: CORALYS is a multicenter, retrospective, observational registry including consecutive patients treated with PCI for ACS. Patients with known history of HF or reduced left ventricular ejection fraction (LVEF) were excluded. Incidence of HF hospitalizations was the primary endpoint. The composite of HF hospitalization or cardiovascular death, and cardiovascular and all-cause death were the secondary endpoints. Predictors of HF hospitalizations and the impact of HF hospitalization on cardiovascular and all-cause death were assessed by means of multivariable Cox proportional hazards model.14699 patients were included. After 2.9 ± 1.8 years, the incidence of HF hospitalizations was 12.7%. Multivariable analysis identified age, diabetes, chronic kidney disease, previous myocardial infarction, atrial fibrillation, pulmonary disease, GRACE risk-score ≥ 141, peripheral artery disease, cardiogenic shock at admission and LVEF ≤40% as independently associated with HF hospitalizations. Complete revascularization was associated with a lower risk of HF (HR 0.46,95%CI 0.39-0.55). HF hospitalization was associated with higher risk of CV and all-cause death (HR 1.89,95%CI 1.5-2.39 and HR 1.85,95%CI 1.6-2.14, respectively). CONCLUSIONS: Incidence of HF hospitalizations among patients treated with PCI for ACS is not negligible and is associated with detrimental impact on patients' prognosis. Several variables may help to assess the risk of HF after ACS.

Bleeding and embolic risk in patients with atrial fibrillation and cancer.

INTRODUCTION AND OBJECTIVES: The impact of cancer on clinical outcomes in patients with atrial fibrillation (AF) is unclear. The aim of this study was to assess how cancer influences the prediction and risk of embolic and hemorrhagic events in patients with AF. METHODS: The study population comprised 16 056 patients from a Spanish health area diagnosed with AF between 2014 and 2018. Of these, 1137 (7.1%) had a history of cancer. During a median follow-up of 4.9 years, we assessed the relationship between cancer and bleeding and embolic events by competing risk analysis, considering death as a competing risk. RESULTS: No association was detected between an increased risk of embolic events and cancer overall (sHR, 0.73; 95%CI, 0.41-1.26), active cancer, or any subgroup of cancer. However, cancer was associated with an increased risk of bleeding, although only in patients with active cancer (sHR, 1.42; 95%CI, 1.20-1.67) or prior radiotherapy (sHR, 1.40; 95%CI, 1.19-1.65). Both the CHA2DS2-VASc and HAS-BLED scores showed suboptimal performance to predict embolic and bleeding risk (c-statistic <0.50), respectively, in nonanticoagulated patients with active cancer. The ratio between the increase in bleeding and the decrease in embolisms with anticoagulation was similar in patients with and without cancer (5.6 vs 7.8; P <.001). CONCLUSIONS: Cancer was not associated with an increased risk of embolic events in AF patients, only with an increased risk of bleeding. However, active cancer worsened the ability of the CHA2DS2-VASc and HAS-BLED scores to predict embolic and bleeding events, respectively, in nonanticoagulated patients.

Nutrition status, obesity and outcomes in patients with atrial fibrillation.

INTRODUCTION AND OBJECTIVES: A paradoxical protective effect of obesity has been previously reported in patients with atrial fibrillation (AF). The aim of this study was to determine the impact of nutritional status and body mass index (BMI) on the prognosis of AF patients. METHODS: We conducted a retrospective population-based cohort study of patients with AF from 2014 to 2017 from a single health area in Spain. The CONUT score was used to assess nutritional status. Cox regression models were used to estimate the association of BMI and CONUT score with mortality. The association with embolism and bleeding was assessed by a competing risk analysis. RESULTS: Among 14 849 AF patients, overweight and obesity were observed in 42.6% and 46.0%, respectively, while malnutrition was observed in 34.3%. During a mean follow-up of 4.4 years, 3335 patients died, 984 patients had a stroke or systemic embolism, and 1317 had a major bleeding event. On univariate analysis, BMI was inversely associated with mortality, embolism, and bleeding; however, this association was lost after adjustment by age, sex, comorbidities, and CONUT score (HR for composite endpoint, 0.98; 95%CI, 0.95-1.01; P=.719). Neither obesity nor overweight were predictors of mortality, embolism, and bleeding events. In contrast, nutritional status-assessed by the CONUT score-was associated with mortality, embolism and bleeding after multivariate analysis (HR for composite endpoint, 1.15; 95%CI, 1.14-1.17; P<.001). CONCLUSIONS: BMI was not an independent predictor of events in patients with AF in contrast to nutritional status, which showed a strong association with mortality, embolism, and bleeding. The study was registered at ClinicalTrials.gov (Identifier: NCT04364516).

Incidence and Predictors of Bleeding in Patients With Cancer and Atrial Fibrillation.

Despite patients with cancer having a higher incidence of atrial fibrillation (AF), little is known about the predictors of outcomes in this population. This study aimed to assess the incidence and predictors of bleeding in patients with AF and cancer. The study population comprised 16,056 patients from a Spanish health area diagnosed with AF between 2014 and 2018 (1,137 with cancer). Competing risk analysis were used to evaluate the association of cancer and bleeding. Discrimination and calibration of bleeding risk scores were assessed by the concordance statistic and the Brier score, respectively. During a median follow-up of 4.9 years, the incidence of bleeding in patients with cancer was 13.2 per 100 patients/year. After multivariate adjustment, a significant association between cancer and bleeding was detected (subdistribution hazard ratio [sHR] 1.18, 95% CI 1.07 to 1.30, p = 0.001), specifically in patients with active cancer or previous radiotherapy. Early age, male gender, diabetes, and anticoagulation were independent predictors of bleeding. However, only anticoagulation with vitamin K antagonist (sHR 1.36, 95% CI 1.03 to 1.78, p = 0.026), not with direct oral anticoagulants (sHR 1.25, 95% CI 0.84 to 1.85, p = 0.270), was associated with bleeding. Discrimination and calibration of Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly, and Drugs/alcohol concomitantly (HAS-BLED), AnTicoagulation and Risk factors In Atrial fibrillation (ATRIA), and Hepatic or renal disease, Ethanol abuse, Malignancy, Older (age ≥75 years), Reduced platelet count or function, Rebleeding risk, Hypertension, Anaemia, Genetic factors, Excessive fall risk and Stroke (HEMORR2HAGES) scores were poor in patients with cancer (concordance statistic <0.6 and Brier score >0.1). In summary, cancer was associated with an increased risk of bleeding in patients with AF. The predictive ability of bleeding risk scores was poor in this population. Anticoagulation with vitamin K antagonist but not with direct oral anticoagulants, was an independent predictor of bleeding in patients with cancer.

Applicability of the Academic Research Consortium for High Bleeding Risk in acute coronary syndrome undergoing percutaneous coronary intervention.

INTRODUCTION AND OBJECTIVES: The recent Academic Research Consortium for High Bleeding Risk (ARC-HBR) proposal did not consider acute coronary syndrome (ACS), by consensus, a bleeding criterion per se despite being a high bleeding risk (HBR) scenario. We investigated the applicability of the ARC-HBR classification and criteria in ACS patients. METHODS: Patients with ACS undergoing coronary stenting between 2012 and 2018 at a tertiary hospital were retrospectively classified as being at HBR if they met ≥ 1 major or ≥ 2 minor ARC-HBR criteria. The primary endpoint was the 1-year cumulative incidence of Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding. RESULTS: Among 4412 patients, 29.5% were at HBR. The incidence of bleeding was higher in the HBR group than in the non-HBR group (9.4% vs 1.3%; P < .01). The rates of in-hospital periprocedural and postdischarge bleeding were also higher in the HBR group (4.3% vs 0.5% and 5.3% vs 0.9%, respectively; P < .01). Bleeding risk gradually increased with increasing ARC-HBR criteria: 1.8%, 5.0%, 9.4%, 16.8%, 25.2%, and 25.9% for 1 isolated minor criterion, ≥ 2 isolated minor criteria, 1 major criterion (isolated or plus 1 minor criterion), 1 major plus ≥ 2 minor criteria, ≥ 2 major criteria (isolated or plus 1 minor criterion), and ≥ 2 major plus ≥ 2 minor criteria, respectively. Sixteen (80%) out of 20 ARC-HBR criteria satisfied the ARC-HBR predefined cutoffs for BARC 3 or 5 bleeding risk. CONCLUSIONS: This study supports the use of the ARC-HBR classification and criteria in the ACS setting. The ARC-HBR classification provides an accurate major bleeding risk estimate and it seems suitable for the identification and management of patients at HBR.

Trade-off between the effects of embolic versus bleeding events on mortality in elderly patients with atrial fibrillation.

INTRODUCTION AND OBJECTIVES: Clinical decision-making on anticoagulation in elderly patients with atrial fibrillation (AF) requires clinicians to consider not only the incidence of embolic and bleeding events, but also the risk of death following these adverse events. We aimed to analyze the trade-off between embolic and bleeding events with respect to mortality in elderly patients with AF. METHODS: The study cohort comprised all patients aged ≥ 75 years from a Spanish health area diagnosed with AF between 2014 and 2017 (n=9365). The risk of death was investigated using Cox proportional hazards models, including embolic and bleeding events as time-dependent binary indicators. RESULTS: During a median follow-up of 4.0 years, both embolic and bleeding events were associated with a higher risk of death (adjusted HR, 2.39; 95%CI, 2.12-2.69; and adjusted HR, 1.79; 95%CI, 1.64-1.96, respectively). The relative risk of death was 33% higher following an embolism than following a bleeding event (rRR, 1.33; 95%CI, 1.15-1.55), although for transient ischemic attack the risk was lower than for bleeding (rRR, 0.79; 95%CI, 0.63-0.99). The risk of death associated with intracranial hemorrhage was similar to that of major embolisms (RR, 1.00; 95%CI, 0.75-1.29). CONCLUSIONS: In elderly AF patients, embolic events appeared to be associated with a higher risk of mortality than extracranial bleeding, except for transient ischemic attacks, which have a better prognosis. For ICH, the mortality risk was similar to that of major embolism.

Rationale and design of the Dapagliflozin after Transcatheter Aortic Valve Implantation (DapaTAVI) randomized trial.

AIMS: Despite aortic stenosis (AS) relief, patients undergoing transcatheter aortic valve implantation (TAVI) are at increased risk of developing heart failure (HF) within first months of intervention. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors have been shown to reduce the risk of HF hospitalization in individuals with diabetes mellitus, reduced left ventricular ejection fraction and chronic kidney disease. However, the effect of SGLT-2 inhibitors on outcomes after TAVI is unknown. The Dapagliflozin after Transcatheter Aortic Valve Implantation (DapaTAVI) trial is designed to assess the clinical benefit and safety of the SGLT-2 inhibitor dapagliflozin in patients undergoing TAVI. METHODS: DapaTAVI is an independent pragmatic, controlled, prospective, randomized, open-label blinded endpoint, multicentre trial conducted in Spain, evaluating the effect of dapagliflozin 10 mg/day on the risk of death and worsening HF in patients with severe AS undergoing TAVI. Candidate patients should have prior history of HF admission plus ≥1 of the following criteria: (i) diabetes mellitus, (ii) left ventricular ejection fraction ≤40%, or (iii) estimated glomerular filtration rate between 25 and 75 ml/min/1.73 m2 . A total of 1020 patients will be randomized (1:1) to dapagliflozin vs. no dapagliflozin. Key secondary outcomes include: (i) incidence rate of individual components of the primary outcome; (ii) cardiovascular mortality; (iii) the composite of HF hospitalization or cardiovascular death; and (iv) total number of HF rehospitalizations. CONCLUSION: DapaTAVI will determine the efficacy and safety of dapagliflozin in a broad spectrum of frail patients after AS relief by TAVI.