Combinational Diuretics in Heart Failure.

PURPOSE OF REVIEW: Diuretics are the cornerstone therapy for acute heart failure (HF) and congestion. Patients chronically exposed to loop diuretics may develop diuretic resistance as a consequence of nephron remodelling, and the combination of diuretics will be necessary to improve diuretic response and achieve decongestion. This review integrates data from recent research and offers a practical approach to current pharmacologic therapies to manage congestion in HF with a focus on combinational therapy. RECENT FINDINGS: Until recently, combined diuretic treatment was based on observational studies and expert opinion. Recent evidence from clinical trials has shown that combined diuretic treatment can be started earlier without escalating the doses of loop diuretics with an adequate safety profile. Diuretic combination is a promising strategy for overcoming diuretic resistance in HF. Further studies aiming to get more insights into the pathophysiology of diuretic resistance and large clinical trials confirming the safety and efficacy over standard diuretics regimens are warranted.

Combining loop with thiazide diuretics for decompensated heart failure: the CLOROTIC trial.

AIMS: To evaluate whether the addition of hydrochlorothiazide (HCTZ) to intravenous furosemide is a safe and effective strategy for improving diuretic response in acute heart failure (AHF). METHODS AND RESULTS: A prospective, double-blind, placebo-controlled trial, including patients with AHF randomized to receive HCTZ or placebo in addition to an intravenous furosemide regimen. The coprimary endpoints were changes in body weight and patient-reported dyspnoea 72 h after randomization. Secondary outcomes included metrics of diuretic response and mortality/rehospitalizations at 30 and 90 days. Safety outcomes (changes in renal function and/or electrolytes) were also assessed. Two hundred and thirty patients (48 women, 83 years) were randomized. Patients assigned to HCTZ were more likely to lose weight at 72 h than those assigned to placebo [2.3 vs. 1.5 kg; adjusted estimated difference (notionally 95 confidence interval) 1.14 (1.84 to 0.42); P 0.002], but there were no significant differences in patient-reported dyspnoea (area under the curve for visual analogue scale: 960 vs. 720; P 0.497). These results were similar 96 h after randomization. Patients allocated to HCTZ showed greater 24 h diuresis (1775 vs. 1400 mL; P 0.05) and weight loss for each 40 mg of furosemide (at 72 and at 96 h) (P 0.001). Patients assigned to HCTZ more frequently presented impaired renal function (increase in creatinine 26.5 moL/L or decrease in eGFR 50; 46.5 vs. 17.2; P 0.001), but hypokalaemia and hypokalaemia were similar between groups. There were no differences in mortality or rehospitalizations. CONCLUSION: The addition of HCTZ to loop diuretic therapy improved diuretic response in patients with AHF.

Prevalence, Related Factors and Association of Left Bundle Branch Block With Prognosis in Patients With Acute Heart Failure: a Simultaneous Analysis in 3 Independent Cohorts.

OBJECTIVES: To determine the prevalence, characteristics and association with prognosis of left bundle branch block (LBBB) in 3 different cohorts of patients with acute heart failure (AHF). METHODS AND RESULTS: We retrospectively analyzed 12,950 patients with AHF who were included in the EAHFE (Epidemiology Acute Heart Failure Emergency), RICA (National Heart Failure Registry of the Spanish Internal Medicine Society), and BASEL-V (Basics in Acute Shortness of Breath Evaluation of Switzerland) registries. We independently analyzed the relationship between baseline and clinical characteristics and the presence of LBBB and the potential association of LBBB with 1-year all-cause mortality and a 90-day postdischarge combined endpoint (Emergency Department reconsultation, hospitalization or death). The prevalence of LBBB was 13.5% (95% confidence interval: 12.9%-14.0%). In all registries, patients with LBBB more commonly had coronary artery disease and previous episodes of AHF, were taking chronic spironolactone treatment, had lower left ventricular ejection fraction and systolic blood pressure values and higher NT-proBNP levels. There were no differences in risk for patients with LBBB in any cohort, with adjusted hazard ratios (95% confidence interval) for 1-year mortality in EAHFE/RICA/BASEL-V cohorts of 1.02 (0.89-1.17), 1.15 (0.95-1.38) and 1.32 (0.94-1.86), respectively, and for 90-day postdischarge combined endpoint of 1.00 (0.88-1.14), 1.14 (0.92-1.40) and 1.26 (0.84-1.89). These results were consistent in sensitivity analyses. CONCLUSIONS: Less than 20% of patients with AHF present LBBB, which is consistently associated with cardiovascular comorbidities, reduced left ventricular ejection fraction and more severe decompensations. Nonetheless, after taking these factors into account, LBBB in patients with AHF is not associated with worse outcomes.

Effectiveness of problem-based learning methodology in undergraduate medical education: a scoping review.

BACKGROUND: Problem-based learning (PBL) is a pedagogical approach that shifts the role of the teacher to the student (student-centered) and is based on self-directed learning. Although PBL has been adopted in undergraduate and postgraduate medical education, the effectiveness of the method is still under discussion. The author's purpose was to appraise available international evidence concerning to the effectiveness and usefulness of PBL methodology in undergraduate medical teaching programs. METHODS: The authors applied the Arksey and O'Malley framework to undertake a scoping review. The search was carried out in February 2021 in PubMed and Web of Science including all publications in English and Spanish with no limits on publication date, study design or country of origin. RESULTS: The literature search identified one hundred and twenty-four publications eligible for this review. Despite the fact that this review included many studies, their design was heterogeneous and only a few provided a high scientific evidence methodology (randomized design and/or systematic reviews with meta-analysis). Furthermore, most were single-center experiences with small sample size and there were no large multi-center studies. PBL methodology obtained a high level of satisfaction, especially among students. It was more effective than other more traditional (or lecture-based methods) at improving social and communication skills, problem-solving and self-learning skills. Knowledge retention and academic performance weren't worse (and in many studies were better) than with traditional methods. PBL was not universally widespread, probably because requires greater human resources and continuous training for its implementation. CONCLUSION: PBL is an effective and satisfactory methodology for medical education. It is likely that through PBL medical students will not only acquire knowledge but also other competencies that are needed in medical professionalism.

Regional differences in the management and outcome of kidney transplantation in patients with human immunodeficiency virus infection: A 3-year retrospective cohort study.

BACKGROUND: In the developed world, kidney transplantation (KT) in patients with human immunodeficiency virus (HIV) infection is well established. Developing countries concentrate 90% of the people living with HIV, but their experience is underreported. Regional differences may affect outcomes. OBJECTIVES: We compared the 3-year outcomes of patients with HIV infection receiving a KT in two different countries, in terms of incomes and development. METHODS: This was an observational, retrospective, double-center study, including all HIV-infected patients >18 years old undergoing KT. RESULTS: Between 2005 and 2015, 54 KTs were performed (39 in a Brazilian center, and 15 in a Spanish center). Brazilians had less hepatitis C virus co-infection (5% vs 27%, P=.024). Median cold ischemia time was higher in Brazil (25 vs 18 hours, P=.001). Biopsy-proven acute rejection (AR) was higher in Brazil (33% vs 13%, P=.187), as were the number of AR episodes (22 vs 4, P=.063). Patient survival at 3 years was 91.3% in Brazil and 100% in Spain; P=.663. All three cases of death in Brazil were a result of bacterial infections within the first year post transplant. At 3 years, survival free from immunosuppressive changes was lower in Brazil (56% vs 90.9%, P=.036). Raltegravir-based treatment to avoid interaction with calcineurin inhibitor was more prevalent in Spain (80% vs 3%; P<.001). HIV infection remained under control in all patients, with undetectable viral load and no opportunistic infections. CONCLUSION: Important regional differences exist in the demographics and management of immunosuppression and antiretroviral therapy. These details may influence AR and infectious complications. Non-AIDS infections leading to early mortality in Brazil deserve special attention.

Rationale and Design of the "Safety and Efficacy of the Combination of Loop with Thiazide-type Diuretics in Patients with Decompensated Heart Failure (CLOROTIC) Trial:" A Double-Blind, Randomized, Placebo-Controlled Study to Determine the Effect of Combined Diuretic Therapy (Loop Diuretics With Thiazide-Type Diuretics) Among Patients With Decompensated Heart Failure.

BACKGROUND: Fluid overload refractory to loop diuretic therapy can complicate acute or chronic heart failure (HF) management. The Safety and Efficacy of the Combination of Loop with Thiazide-type Diuretics in Patients with Decompensated Heart Failure (CLOROTIC) trial (Clinicaltrials.gov identifier NCT01647932) will test the hypothesis that blocking distal tubule sodium reabsorption with hydrochlorothiazide can antagonize the renal adaptation to chronic loop diuretic therapy and improve diuretic resistance. METHODS: CLOROTIC is a randomized, placebo-controlled, double-blind, multicenter study. Three hundred and four patients with decompensated HF will be randomly assigned to receive hydrochlorothiazide or placebo in addition to a furosemide regimen. The main inclusion criteria are: age ≥18 years, history of chronic HF (irrespective of etiology and/or ejection fraction), admission for acute decompensation, and previous treatment with an oral loop diuretic for at least 1 month before randomization. The 2 coprimary endpoints are changes in body weight and changes in patient-reported dyspnea during hospital admission. Morbidity, mortality, and safety aspects will also be addressed. CONCLUSIONS: CLOROTIC is the first large-scale trial to evaluate whether the addition of a thiazide diuretic (hydrochlorothiazide) to a loop diuretic (furosemide) is a safe and effective strategy for improving congestive symptoms resulting from HF. This trial will provide important information and will therefore have a major impact on treatment strategies and future trials in these patients.

Heart Failure with Recovered Ejection Fraction in a Cohort of Elderly Patients with Chronic Heart Failure.

OBJECTIVE: The aim of this study was to determine whether patients with heart failure (HF) who recover left ventricular ejection fraction (LVEF), termed here as 'Rec-HF', have a distinct clinical profile and prognosis compared with patients with HF and reduced LVEF (HF-REF) or HF and preserved LVEF (HF-PEF). METHODS: We evaluated and classified patients from the Spanish Heart Failure Registry into three categories based on enrollment/follow-up echocardiograms: HF-PEF (LVEF ≥50%), HF-REF (LVEF persistently <50%) and Rec-HF (LVEF on enrollment <50% but normalized during follow-up). RESULTS: A total of 1,202 patients were included, 1,094 with HF-PEF, 81 with HF-REF and 27 with Rec-HF. The three groups included patients of advanced age (mean age 75 years) with comorbidities. Rec-HF patients were younger, with a better functional status, lower prevalence of diabetes mellitus, dementia and cerebrovascular disease, and higher prevalence of COPD. The etiology of HF was more frequently ischemic and alcoholic and less frequently hypertensive. After a median follow-up of 367 days, the unadjusted hazard ratios for death in the Rec-HF versus HF-PEF and HF-REF groups were 0.11 (95% CI 0.02-080; p = 0.029) and 0.31 (95% CI 0.04-2.5; p = 0.274). Results were statistically nonsignificant in multivariate-adjusted models. CONCLUSION: Rec-HF is also present in elderly patients with HF but it is necessary to further investigate the natural history and optimal pharmacologic management of this 'new HF syndrome'.

The utility of heart failure registries: a descriptive and comparative study of two heart failure registries.

BACKGROUND AND AIM: Registries are useful to address questions that are difficult to answer in clinical trials. The objective of this study was to describe and compare two heart failure (HF) cohorts from two Spanish HF registries. METHODS: We compared the RICA and EAHFE registries, both of which are prospective multicentre cohort studies including patients with decompensated HF consecutively admitted to internal medicine wards (RICA) or attending the emergency department (EAHFE). From the latter registry we only included patients who were admitted to internal medicine wards. RESULTS: A total of 5137 patients admitted to internal medicine wards were analysed (RICA: 3287 patients; EAHFE: 1850 patients). Both registries included elderly patients (RICA: mean (SD) age 79 (9) years; EAHFE: mean (SD) age 81 (9) years), with a slight predominance of female gender (52% and 58%, respectively, in the RICA and EAHFE registries) and with a high proportion of patients with preserved ejection fraction (58% and 62%, respectively). Some differences in comorbidities were noted, with diabetes mellitus, dyslipidaemia, chronic renal failure and atrial fibrillation being more frequent in the RICA registry while cognitive and functional impairment predominated in the EAHFE registry. The 30-day mortality after discharge was 3.4% in the RICA registry and 4.8% in the EAHFE registry (p<0.05) and the 30-day readmission rate was 7.5% in the RICA registry (readmission to hospital) and 24.0% in the EAHFE registry (readmission to emergency department) (p<0.001). CONCLUSIONS: We found differences in the clinical characteristics of patients admitted to Spanish internal medicine wards for decompensated HF depending on inclusion in either the RICA or EAHFE registry.

Prognosis of acute heart failure in patients followed up in nursing homes in Spain: Results from the RICA registry.

BACKGROUND: Patients with chronic diseases such as heart failure (HF) are at risk of hospital admission. We evaluated the impact of living in nursing homes (NH) on readmissions and all-cause mortality of HF patients during a one-year follow up. METHODS: An observational and multicenter study from the Spanish National Registry of Heart Failure (RICA) was performed. We compared clinical and prognostic characteristics between both groups. Bivariate analyses were performed using Student's t-test and Tukey's method and a Kaplan-Meier survival at one-year follow up. A multivariate proportional hazards analysis of [Cox] regression by the conditional backward method was conducted for the variables being statistically significant related to the probability of death in the univariate. RESULTS: There were 5644 patients included, 462 (8.2%) of whom were nursing home residents. There were 52.7% women and mean age was 79.7±8.8 years. NH residents had lower Barthel (74.07), Charlson (3.27), and Pfeiffer index (2.2), p<0.001). Mean pro-BNP was 6686pg/ml without statistical significance differences between groups. After 1-year follow-up, crude analysis showed no differences in readmissions 74.7% vs. 72.3%, p=0.292, or mortality 63.9% vs. 61.1%, p=0.239 between groups. However, after controlling for confounding variables, NH residents had a higher 1-year all-cause mortality (HR 1.153; 95% CI 1.011-1.317; p=0.034). Kaplan-Meier analysis showed worse survival in nursing home residents (log-rank of 7.12, p=0.008). CONCLUSIONS: Nursing home residents with heart failure showed higher one-year mortality which could be due to worse functional status, higher comorbidity, and cognitive deterioration.

Combining Loop and Thiazide Diuretics Across the Left Ventricular Ejection Fraction Spectrum: The CLOROTIC Trial.

BACKGROUND: The addition of hydrochlorothiazide (HCTZ) to furosemide in the CLOROTIC (Combining Loop with Thiazide Diuretics for Decompensated Heart Failure) trial improved the diuretic response in patients with acute heart failure (AHF). OBJECTIVES: This work aimed to evaluate if these results differ across the spectrum of left ventricular ejection fraction (LVEF). METHODS: This post hoc analysis of the randomized, double-blind, placebo-controlled CLOROTIC trial enrolled 230 patients with AHF to receive either HCTZ or a placebo in addition to an intravenous furosemide regimen. The influence of LVEF on primary and secondary outcomes was evaluated. RESULTS: The median LVEF was 55%: 166 (72%) patients had LVEF >40%, and 64 (28%) had LVEF ≤40%. Patients with a lower LVEF were younger, more likely to be male, had a higher prevalence of ischemic heart disease, and had higher natriuretic peptide levels. The addition of HCTZ to furosemide was associated with the greatest weight loss at 72 of 96 hours, better metrics of diuretic response, and greater 24-hour diuresis compared with placebo, with no significant differences according to the LVEF category (using 2 LVEF cutoff points: 40% and 50%) or LVEF as a continuous variable (all P values were insignificant). There were no significant differences observed with the addition of HCTZ in terms of mortality, rehospitalizations, or safety endpoints (impaired renal function, hyponatremia, and hypokalemia) among the 2 LVEF groups (all P values were insignificant). CONCLUSIONS: Adding HCTZ to intravenous furosemide seems to be effective strategy for improving diuretic response in AHF without treatment effect modification according to baseline LVEF. (Combining Loop with Thiazide Diuretics for Decompensated Heart Failure [CLOROTIC], NCT01647932; Randomized, double blinded, multicenter study, to asses Safety and Efficacy of the Combination of Loop With Thiazide-type Diuretics vs Loop diuretics with placebo in Patients With Decompensated, EudraCT Number 2013-001852-36).

The two different profiles in heart failure with preserved ejection fraction and type 2 diabetes mellitus: ischemic and diabetic.

OBJECTIVE: Two profiles of patients with heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes mellitus (T2DM) can be discerned: those with ischemic and those with diabetic cardiomyopathy (DMC). We aim to analyze clinical differences and prognosis between patients of these two profiles. MATERIAL AND METHODS: This cohort study analyzes data from the Spanish Heart Failure Registry, a multicenter, prospective registry that enrolled patients admitted for decompensated heart failure and followed them for one year. Three groups were created according to the presence of T2DM and heart disease depending on the etiology (ischemic when coronary artery disease was present, or DMC when no coronary, valvular, or congenital heart disease; no hypertension; nor infiltrative cardiovascular disease observed on an endomyocardial biopsy). The groups and outcomes were compared. RESULTS: A total of 466 patients were analyzed. Group 1 (n = 210) included patients with ischemic etiology and T2DM. Group 2 (n = 112) included patients with DMC etiology and T2DM. Group 3 (n = 144), a control group, included patients with ischemic etiology and without T2DM. Group 1 had more hypertension and dyslipidemia; group 2 had more atrial fibrillation (AF) and higher body mass index; group 3 had more chronic kidney disease and were older. In the regression analysis, group 3 had a better prognosis than group 1 (reference group) for cardiovascular mortality and HF readmissions (HR 0.44;95%CI 0.2-1; p = .049). CONCLUSIONS: Patients with T2DM and HFpEF, who had the poorest prognosis, were of two different profiles: either ischemic or DMC etiology. The first had a higher burden of cardiovascular disease and inflammation whereas the second had a higher prevalence of obesity and AF. The first had a slightly poorer prognosis than the second, though this finding was not significant.

Practical Approaches to the Management of Cardiorenal Disease beyond Congestion.

BACKGROUND: The coexistence of heart and kidney diseases, also called cardiorenal syndrome, is very common, leads to increased morbidity and mortality, and poses diagnostic and therapeutic difficulties. There is a risk-treatment paradox, such that patients with the highest risk are treated with lesser disease-modifying medical therapies. SUMMARY: In this document, different scientific societies propose a practical approach to address and optimize cardiorenal therapies and related comorbidities systematically in chronic cardiorenal disease beyond congestion. Cardiorenal programs have emerged as novel models that may assist in delivering coordinated and holistic management for these patients. KEY MESSAGES: (1) Cardiorenal disease is a ubiquitous entity in clinical practice and is associated with numerous barriers that limit medical treatment. (2) The present article focuses on the practical approaches to managing chronic cardiorenal disease beyond congestion to overcome some of these barriers and improve the treatment of this high-risk population.

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.).

The significance of metabolic alkalosis on acute decompensated heart failure: the ALCALOTIC study.

AIMS: To determine the prevalence and the impact on prognosis of metabolic alkalosis (MA) in patients admitted for acute heart failure (AHF). METHODS AND RESULTS: The ALCALOTIC is a multicenter, observational cohort study that prospectively included patients admitted for AHF. Patients were classified into four groups according to their acid-base status on admission: acidosis, MA, respiratory alkalosis, and normal pH (reference group for comparison). Primary endpoint was all-cause in-hospital mortality, and secondary endpoints included 30/90-day all-cause mortality, all-cause readmission, and readmission for HF. Associations between endpoints and acid-base alterations were estimated in a multivariate Cox regression model including sex, age, comorbidities, and Barthel index and expressed as hazard ratio (HR) with 95% confidence interval (95% CI). Six hundred sixty-five patients were included (84 years and 57% women), and 40% had acid-base alterations on admission: 188 (28%) acidosis and 78 (12%) alkalosis. The prevalence (95% CI) of MA was 9% (6.8-11.2%). Patients with MA were more women; had fewer comorbidities, better renal function, and higher left ventricle ejection fraction values; and received more treatment with oral acetazolamide during hospitalization and at discharge. MA was not associated with a higher risk of in-hospital mortality and 30/90-day all-cause mortality or readmissions but was associated with a significant increase in readmissions for HF at 30 and 90 days (adjusted HR [95% CI] 3.294 [1.397-7.767], p = 0.006 and 2.314 [1.075-4.978], p = 0.032). CONCLUSION: The prevalence of MA in patients admitted for AHF was 9%, and its presence was associated with more readmissions for HF but not with all-cause mortality.

Combining loop with thiazide diuretics in patients discharged home after a heart failure decompensation: Association with 30-day outcomes.

OBJECTIVE: To investigate the association of the addition of thiazide diuretic on top of loop diuretic and standard of care with short-term outcomes of patients discharged after surviving an acute heart failure (AHF) episode. METHODS: This is a secondary analysis of 14,403 patients from three independent cohorts representing the main departments involved in AHF treatment for whom treatment at discharge was recorded and included loop diuretics. Patients were divided according to whether treatment included or not thiazide diuretics. Short-term outcomes consisted of 30-day all-cause mortality, hospitalization (with a separate analysis for hospitalization due to AHF or to other causes) and the combination of death and hospitalization. The association between thiazide diuretics on short-term outcomes was explored by Cox regression and expressed as hazard ratios (HR) with 95 % confidence intervals, which were adjusted for 18 patient-related variables and 9 additional drugs (aside from loop and thiazide diuretics) prescribed at discharge. RESULTS: The median age was 81 (interquartile range=73-86) years, 53 % were women, and patients were mainly discharged from the cardiology (42 %), internal medicine or geriatric department (29 %) and emergency department (19 %). There were 1,367 patients (9.5 %) discharged with thiazide and loop diuretics, while the rest (13,036; 90.5 %) were discharged with only loop diuretics on top of the remaining standard of care treatments. The combination of thiazide and loop diuretics showed a neutral effect on all outcomes: death (adjusted HR 1.149, 0.850-1.552), hospitalization (0.898, 0.770-1.048; hospitalization due to AHF 0.799, 0.599-1.065; hospitalization due to other causes 1.136, 0.756-1.708) and combined event (0.934, 0.811-1.076). CONCLUSION: The combination of thiazide and loop diuretics was not associated with changes in risk of death, hospitalization or a combination of both.

The prognostic significance of bundle branch block in acute heart failure: a systematic review and meta-analysis.

AIMS: The aim of this study was to conduct a meta-analysis of prospective studies assessing the relationship between bundle branch block (BBB) or wide QRS and risk of all-cause mortality in patients with acute heart failure (AHF). METHODS AND RESULTS: We searched the PubMed, Scopus and Web of Science database from inception to February 2022 to identify single centre or multicentre studies including a minimum of 400 patients and assessing the association between BBB or wide QRS and mortality in patients with AHF. Study-specific hazard ratio (HR) estimates were combined using a random-effects meta-analysis. Two meta-analyses were performed: (1) grouping by conduction disturbance and follow-up length and, (2) using the results from the longest follow-up for each study and grouping by the type of BBB. The meta-analysis included 21 publications with a total of 116,928 patients. Wide QRS (considering right (RBBB) and left (LBBB) altogether) was associated with a significant increment in the risk of all-cause mortality (pooled adjusted HR 1.112, 95% CI 1.065-1.160). The increased risk of death was also present when LBBB (HR 1.121, 95% CI 1.042-1.207) and RBBB (HR 1.187, 95% CI 1.045-1.348) were considered individually. There was no difference in risk between LBBB and RBBB (P for interaction = 0.533). Other outcomes including sudden death, rehospitalization and a combination of cardiovascular death or rehospitalization were also increased in patients with BBB or wide QRS. CONCLUSIONS: This meta-analysis suggests a modest increase in the risk of all-cause mortality among patients with AHF and BBB or wide QRS, irrespective of the type of BBB.

The influence of comorbidities on the prognosis after an acute heart failure decompensation and differences according to ejection fraction: Results from the EAHFE and RICA registries.

OBJECTIVE: The role of comorbidities in heart failure (HF) outcome has been previously investigated, although mostly individually. We investigated the individual effect of 13 comorbidities on HF prognosis and looked for differences according to left-ventricular ejection fraction (LVEF), classified as reduced (HFrEF), mildly-reduced (HFmrEF) and preserved (HFpEF). METHODS: We included patients from the EAHFE and RICA registries and analysed the following comorbidities: hypertension, dyslipidaemia, diabetes mellitus (DM), atrial fibrillation (AF), coronary artery disease (CAD), chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), heart valve disease (HVD), cerebrovascular disease (CVD), neoplasia, peripheral artery disease (PAD), dementia and liver cirrhosis (LC). Association of each comorbidity with all-cause mortality was assessed by an adjusted Cox regression analysis that included the 13 comorbidities, age, sex, Barthel index, New York Heart Association functional class and LVEF and expressed as adjusted Hazard Ratios (HR) with 95% confidence intervals (95%CI). RESULTS: We analysed 8,336 patients (82 years-old; 53% women; 66% with HFpEF). Mean follow-up was 1.0 years. Respect to HFrEF, mortality was lower in HFmrEF (HR:0.74;0.64-0.86) and HFpEF (HR:0.75;0.68-0.84). Considering patients all together, eight comorbidities were associated with mortality: LC (HR:1.85;1.42-2.42), HVD (HR:1.63;1.48-1.80), CKD (HR:1.39;1.28-1.52), PAD (HR:1.37;1.21-1.54), neoplasia (HR:1.29;1.15-1.44), DM (HR:1.26;1.15-1.37), dementia (HR:1.17;1.01-1.36) and COPD (HR:1.17;1.06-1.29). Associations were similar in the three LVEF subgroups, with LC, HVD, CKD and DM remaining significant in the three subgroups. CONCLUSION: HF comorbidities are associated differently with mortality, LC being the most associated with mortality. For some comorbidities, this association can be significantly different according to the LVEF.

Combining loop and thiazide diuretics for acute heart failure across the estimated glomerular filtration rate spectrum: A post-hoc analysis of the CLOROTIC trial.

AIMS: In patients with acute heart failure (AHF), the addition of hydrochlorothiazide (HCTZ) to furosemide improved diuretic response in the CLOROTIC trial. This work aimed to evaluate if these effects differ across the estimated glomerular filtration rate (eGFR) spectrum. METHODS AND RESULTS: This post-hoc analysis of the CLOROTIC trial analysed 230 patients with AHF and explored the influence of eGFR on primary and secondary endpoints. The median eGFR was 43 ml/min/1.73 m2 (range 14-109) and 23% had eGFR ≥60 ml/min/1.73 m2 (group 1), 24% from 45 to 59 ml/min/1.73 m2 (group 2), and 53% <45 ml/min/1.73 m2 (group 3). Patients treated with HCTZ had greatest weight loss at 72 h in all three groups, but patients in group 1 had a significantly greater response (-2.1 kg [-3.0 to 0.5]), compared to patients in groups 2 (-1.3 kg [-2.3 to 0.2]) and 3 (-0.1 kg [-1.3 to 0.4]) (p-value for interaction = 0.246). At 96 h, the differences in weight were -1.8 kg (-3.0 to -0.3), -1.4 kg (-2.6 to 0.3), and -0.5 kg (-1.3 to -0.1) in groups 1, 2, and 3, respectively (p-value for interaction = 0.256). There were no significant differences observed with the addition of HCTZ in terms of diuretic response, mortality or rehospitalizations, or safety endpoints (impaired renal function, hyponatraemia, and hypokalaemia) among the three eGFR groups (all p-values for interaction were no significant). CONCLUSION: The addition of eGFR-adjusted doses of oral HCTZ to loop diuretics in patients with AHF improved diuretic response across the eGFR spectrum. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT01647932; EudraCT number: 2013-001852-36.

QT interval and short-term outcome in acute heart failure.

OBJECTIVE: To investigate the association of corrected QT (QTc) interval duration and short-term outcomes in patients with acute heart failure (AHF). METHODS: We analyzed AHF patients enrolled in 11 Spanish emergency departments (ED) for whom an ECG with QTc measurement was available. Patients with pace-maker rhythm were excluded. Primary outcome was 30-day all-cause mortality and secondary outcomes were need of hospitalization, in-hospital mortality and prolonged hospitalization (> 7 days). Association between QTc and outcomes was explored by restricted cubic spline (RCS) curves. Results were expressed as odds ratios (OR) and 95%CI adjusted by patients baseline and decompensation characteristics, using a QTc = 450 ms as reference. RESULTS: Of 1800 patients meeting entry criteria (median age 84 years (IQR = 77-89), 56% female), their median QTc was 453 ms (IQR = 422-483). The 30-day mortality was 9.7%, while need of hospitalization, in-hospital mortality and prolonged hospitalization were 77.8%, 9.0% and 50.0%, respectively. RCS curves found longer QTc was associated with 30-day mortality if > 561 ms, OR = 1.86 (1.00-3.45), and increased up to OR = 10.5 (2.25-49.1), for QTc = 674 ms. A similar pattern was observed for in-hospital mortality; OR = 2.64 (1.04-6.69), for QTc = 588 ms, and increasing up to OR = 8.02 (1.30-49.3), for QTc = 674 ms. Conversely, the need of hospitalization had a U-shaped relationship: being increased in patients with shorter QTc [OR = 1.45 (1.00-2.09) for QTc = 381 ms, OR = 5.88 (1.25-27.6) for the shortest QTc of 200 ms], and also increasing for prolonged QTc [OR = 1.06 (1.00-1.13), for QTc = 459 ms, and reaching OR = 2.15 (1.00-4.62) for QTc = 588 ms]. QTc was not associated with prolonged hospitalization. CONCLUSION: In ED AHF patients, initial QTc provides independent short-term prognostic information, with increasing QTc associated with increasing mortality, while both, shortened and prolonged QTc are associated with need of hospitalization.