Endocarditis infecciosa en pacientes con prolapso valvular mitral y válvula aórtica bicúspide

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Medicina. Fecha de lectura: 11-09-201

Quantification and Treatment of Congestion in Heart Failure : A Clinical and Pathophysiological Overview Cuantificación y tratamiento de la congestión en insuficiencia cardíaca: una visión clínica y fisiopatológica

Renal sodium and water retention with resulting extracellular volume expansion and redistribution are hallmark features of heart failure syndromes. However, congestion assessment, monitoring, and treatment represent a real challenge in daily clinical practice. This document reviewed historical and contemporary evidence of available methods for determining volume status and discuss pharmacological aspects and pathophysiological principles that underlie diuretic use

Systematic review and meta-analysis of surgical outcomes comparing mechanical valve replacement and bioprosthetic valve replacement in infective endocarditis

Infective endocarditis (IE) is an infection involving either native or prosthetic heart valves, the endocardial surface of the heart or any implanted intracardiac devices. IE is a rare condition affecting 3-15 patients per 100,000 population. In-hospital mortality rates in patients with IE remain high at around 20% despite treatment advances. There is no consensus recommendation favoring either bioprosthetic valve or mechanical valve implantation in the setting of IE; patient age, co-morbidities and preferences should be considered selecting the replacement prosthesis. A systematic review and meta-analysis of studies reporting the outcomes of patients undergoing bioprosthetic or mechanical valve replacement for infective endocarditis with data extracted for overall survival, valve reinfection rates and valve reoperation. Eleven relevant studies were identified, with 2,336 patients receiving a mechanical valve replacement and 2,057 patients receiving a bioprosthetic valve replacement. There was no significant difference for overall survival between patients treated with mechanical valves and those treated with bioprosthetic valves [hazard ratio (HR) 0.94, 95% confidence interval (CI): 0.73-1.21, P=0.62]. There was no significant difference in reoperation rates between patients treated with a bioprosthetic valve and those treated with a mechanical valve (HR 0.82, 95% CI: 0.34-1.98, P=0.66) and there was no significant difference in the rate of valve reinfection rates (HR 0.95, 95% CI: 0.48-1.89, P=0.89). The presence of infective endocarditis alone should not influence the decision of which type of valve prosthesis that should be implanted. This decision should be based on patient age, co-morbidities and preferences

A simple score to identify super-responders to sacubitril/valsartan in ambulatory patients with heart failure

Introduction: Sacubitril/valsartan (SV) promotes cardiac remodeling and improves prognosis in patients with heart failure (HF). However, the response to the drug may vary between patients and its implementation in daily clinical practice has been slower than expected. Our objective was to develop a score predicting the super-response to SV in HF outpatients. Methods: This is a retrospective analysis of 185 consecutive patients prescribed SV from two tertiary hospitals between September 2016 and February 2018. Super-responder was defined as a patient taking the drug and (i) without HF admissions, death, or heart transplant, and (ii) with a ≥50% reduction in NT-proBNP levels and/or an increase of ≥10 points in LVEF in a 12-month follow-up period after starting SV. Clinical, echocardiographic, ECG, and biochemical variables were used in a logistic regression analysis to construct a score for super-response to SV which was internally validated using bootstrap method. Results: Out of 185 patients, 65 (35%) fulfilled the super-responder criteria. Predictors for super-response to SV were absence of both previous aldosterone antagonist and diuretic treatment, NYHA I-II class, female gender, previous 1-year HF admission, and sinus rhythm. An integrating score distinguished a low- (80%) for 1-year super-response to SV. The AUC for the model was 0.72 (95%CI: 0.64-0.80), remaining consistent after internal validation. Conclusion: One-third of our patients presented a super-response to SV. We propose an easy-to-calculate score to predict super-response to SV after 1-year initiation based on variables that are currently assessed in clinical practice

β3 adrenergic agonist treatment in chronic pulmonary hypertension associated with heart failure (SPHERE-HF): a double blind, placebo-controlled, randomized clinical trial.

AIMS Pulmonary hypertension (PH) associated with left heart disease is an increasingly prevalent problem, orphan of targeted therapies, and related to a poor prognosis, particularly when pre- and post-capillary PH combine. The current study aimed to determine whether treatment with the selective β3 adrenoreceptor agonist mirabegron improves outcomes in patients with combined pre- and post-capillary PH (CpcPH). METHODS AND RESULTS The β3 Adrenergic Agonist Treatment in Chronic Pulmonary Hypertension Secondary to Heart Failure (SPHERE-HF) trial is a multicentre, randomized, parallel, placebo-controlled clinical trial that enrolled stable patients with CpcPH associated with symptomatic heart failure. A total of 80 patients were assigned to receive mirabegron (50 mg daily, titrated till 200 mg daily, n = 39) or placebo (n = 41) for 16 weeks. Of them, 66 patients successfully completed the study protocol and were valid for the main analysis. The primary endpoint was the change in pulmonary vascular resistance (PVR) on right heart catheterization. Secondary outcomes included the change in right ventricular (RV) ejection fraction by cardiac magnetic resonance or computed tomography, other haemodynamic variables, functional class, and quality of life. The trial was negative for the primary outcome (placebo-corrected mean difference of 0.62 Wood units, 95% confidence interval [CI] -0.38, 1.61, p = 0.218). Patients receiving mirabegron presented a significant improvement in RV ejection fraction as compared to placebo (placebo-corrected mean difference of 3.0%, 95% CI 0.4, 5.7%, p = 0.026), without significant differences in other pre-specified secondary outcomes. CONCLUSIONS SPHERE-HF is the first clinical trial to assess the potential benefit of β3 adrenergic agonists in PH. The trial was negative since mirabegron did not reduce PVR, the primary endpoint, in patients with CpcPH. On pre-specified secondary outcomes, a significant improvement in RV ejection fraction assessed by advanced cardiac imaging was found, without differences in functional class or quality of life.The SPHERE-HF trial is an investigator-initiated noncommercial trial independent of the pharmaceutical industry. This work was funded by a grant from Fundació La Marató de TV3 (20151730-31-32) to A.G.-A. as the coordinator. A.G.A. was granted by Instituto de Salud Carlos III INT19/00022, PI17/00995 and PI20/00742 during the study period. B.I. is funded by the European Commission (ERC-Consolidator Grant agreement No. 819775), the Spanish Ministry of Science and Innovation (PID2019-110369RB-I00), and the Comunidad de Madrid (S2017/BMD-3867 RENIM-CM). The CNIC is supported by the Ministerio de Ciencia, Innovación y Universidades and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (CEX2020-001041-S). CNIC imaging facilities are part of the ICTS ReDIB. IDIBAPS belongs to the CERCA Programme and receives partial funding from the Generalitat de Catalunya. The study funders were not involved in the study design; the collection, analysis, or interpretation of data; the writing of the manuscript; or the decision to submit the paper to publication. Conflict of interest: CNIC and Fundació Clínic per a la recerca biomèdica hold a patent for the use of beta-3 agonists for the treatment of pulmonary hypertension (B.I., A.G.A., and V.F. are co-inventors). All other authors have nothing to disclose.S

Utility of the IMPACT score for predicting heart transplant mortality: analysis on a contemporary cohort of the Spanish Heart Transplant Registry

[Abstract] Introduction and objectives: The Index for Mortality Prediction After Cardiac Transplantation (IMPACT) score was derived and validated as a predictor of mortality after heart transplantation (HT). The primary objective of this work is to externally validate the IMPACT score in a contemporary Spanish cohort. Methods: Spanish Heart Transplant Registry data were used to identify adult (>16 years) HT patients between January 2000 and December 2015. Retransplantation, multiorgan transplantation and patients in whom at least one of the variables required to calculate the IMPACT score was missing were excluded from the analysis (N = 2810). Results: Median value of the IMPACT score was five points (IQR: 3, 8). Overall, 1-year survival rate was 79.1%. Kaplan-Meier 1-year survival rates by IMPACT score categories (0-2, 3-5, 6-9, 10-14, ≥15) were 84.4%, 81.5%, 79.3%, 77.3%, and 58.5%, respectively (Log-Rank test: p < .001). Performance analysis showed a good calibration (Hosmer-Lemeshow chi-square for 1 year was 7.56; p = .47) and poor discrimination ability (AUC-ROC .59) of the IMPACT score as a predictive model. Conclusions: In a contemporary Spanish cohort, the IMPACT score failed to accurately predict the risk of death after HT

Rationale and Design of the Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure Study

Aims: Although acute heart failure (AHF) with volume overload is treated with loop diuretics, their dosing and type of administration are mainly based upon expert opinion. A recent position paper from the Heart Failure Association (HFA) proposed a step-wise pharmacologic diuretic strategy to increase the diuretic response and to achieve rapid decongestion. However, no study has evaluated this protocol prospectively. Methods and results: The Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure (ENACT-HF) study is an international, multicentre, non-randomized, open-label, pragmatic study in AHF patients on chronic loop diuretic therapy, admitted to the hospital for intravenous loop diuretic therapy, aiming to enrol 500 patients. Inclusion criteria are as follows: at least one sign of volume overload (oedema, ascites, or pleural effusion), use ≥ 40 mg of furosemide or equivalent for >1 month, and a BNP > 250 ng/L or an N-terminal pro-B-type natriuretic peptide > 1000 pg/L. The study is designed in two sequential phases. During Phase 1, all centres will treat consecutive patients according to the local standard of care. In the Phase 2 of the study, all centres will implement a standardized diuretic protocol in the next cohort of consecutive patients. The protocol is based upon the recently published HFA algorithm on diuretic use and starts with intravenous administration of two times the oral home dose. It includes early assessment of diuretic response with a spot urinary sodium measurement after 2 h and urine output after 6 h. Diuretics will be tailored further based upon these measurements. The study is powered for its primary endpoint of natriuresis after 1 day and will be able to detect a 15% difference with 80% power. Secondary endpoints are natriuresis and diuresis after 2 days, change in congestion score, change in weight, in-hospital mortality, and length of hospitalization. Conclusions: The ENACT-HF study will investigate whether a step-wise diuretic approach, based upon early assessment of urinary sodium and urine output as proposed by the HFA, is feasible and able to improve decongestion in AHF with volume overload