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.

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 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.

Benefits of dapagliflozin in the whole spectrum of heart failure in clinical practice: the RICA registry.

Aims: To determine the projected benefits of dapagliflozin after an acute heart failure (HF) event in Spain. Methods: A multicenter and prospective study that included subjects aged 50 years or older consecutively admitted with HF to internal medicine departments in Spain. The projected clinical benefits of dapagliflozin were calculated via pooled analysis of the DAPA-HF and DELIVER trials. Results: A total of 5644 subjects were analyzed, of whom 79.2% were eligible for dapagliflozin, according to criteria of the DAPA-HF and DELIVER trials. Full implementation of dapagliflozin would imply a 1-year absolute risk reduction of 2.3% for death (number needed to treat = 43) and 5.7% (number needed to treat = 17) for HF rehospitalization. Conclusion: Treatment with dapagliflozin could significantly reduce HF burden in clinical practice.

Heart failure is a severe condition that is associated with a high risk of complications. This means that it is important to start using new therapies that have demonstrated a clinical benefit. Clinical trials have shown that dapagliflozin reduces the risk of developing these complications in patients with heart failure. However, it is important to find out whether the results of clinical trials are also seen in real-life populations. We estimated the potential benefits of dapagliflozin in people admitted to hospital more than once with heart failure. The study took place in Spain. Our data suggest that treatment with dapagliflozin could reduce the complications associated with heart failure in real-life patients.

Prognostic Impact of the UMIPIC Program in the Follow Up in Patients with Heart Failure and Cardiorenal Syndrome.

BACKGROUND: Individuals suffering from heart failure (HF) and cardiorenal syndrome (CRS) represent a special group of patients considering their age, multiple health issues, and treatment challenges. These factors make them more susceptible to frequent hospital stays and a higher mortality rate. UMIPIC is a multidisciplinary care model program for patients with heart failure follow up provided by internists and nurses who are experts in this entity. Our study delved into the effectiveness of this specialized care program (UMIPIC) in mitigating these risks for HF and CRS patients. METHODS: We analyzed the medical records of 3255 patients diagnosed with HF and CRS types 2 and 4, sourced from the RICA registry. These patients were divided into two distinct groups: those enrolled in the UMIPIC program (1205 patients) and those under standard care (2050 patients). Using propensity score matching, we ensured that both groups were comparable. The study focused on tracking hospital admissions and mortality rates for one year after an HF-related hospital stay. RESULTS: Patients in the UMIPIC group experienced fewer hospital readmissions due to HF compared to their counterparts (20% vs. 32%; Hazard Ratio [HR] = 0.48; 95% Confidence Interval [95% CI]: 0.40-0.57; p < 0.001). They also showed a lower mortality rate (24% vs. 36%; HR = 0.64; 95% CI: 0.54-0.75; p < 0.001). Furthermore, the UMIPIC group had fewer total hospital admissions (36% vs. 47%; HR = 0.58; 95% CI: 0.51-0.66; p < 0.001). CONCLUSIONS: The UMIPIC program, centered on holistic and ongoing care, effectively reduces both hospital admissions and mortality rates for HF and CRS patients after a one-year follow-up period.

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.

[Influence of the degree of anaemia on the prognosis of older adults with heart failure (SPAN-HF study)]. / Influencia del grado de anemia en el pronóstico de los pacientes de edad avanzada con insuficiencia cardíaca (Estudio SPAN-HF).

OBJECTIVE: To assess whether a sustained optimal haemoglobin value in the 3 months after admission for heart failure (HF) decompensation reduces morbidity and mortality during the 12 months after admission for acute HF. PATIENTS AND METHOD: Retrospective study of the 1408 patients older than 65 years included in the RICA registry divided into 3 groups: no anaemia (group A), recovered anaemia (group B), and persistent anaemia (group C), according to haemoglobin levels on admission, and 3 months after discharge. Kaplan-Meier curves were constructed, comparing the groups using the log-rank test and a Cox regression model was performed to analyse survival. RESULTS: 578 (41.1%), 299 (21.2%) and 531 (37.7%) were included in groups A, B and C, respectively. We recorded a total of 768 deaths and readmissions. There were 23 (4%), 12 (4%) and 49 (9.2%), (p=.001) individuals who died due to HF and 154 (27%), 73 (24%) and 193 (36%) (P<.001) admissions for this pathology, respectively. Patients with persistent anaemia had a higher risk of death (RR 1.29, 95% CI 1.04-1.61, P=.024) or readmission (1.92, 95% CI 1.16-3, 19; P=.012) due to HF. CONCLUSIONS: Persistent anaemia in the months after admission for HF increases morbidity and mortality in the subsequent year.

Heart failure with mid-range ejection fraction in patients admitted to internal medicine departments: Findings from the RICA Registry.

AIM: To improve the knowledge on characteristics, treatment and prognosis in patients with heart failure (HF) and mid-range ejection fraction discharged after an acute HF episode. METHODS: We prospectively included and followed 2753 patients admitted with HF to Internal Medicine units. Patients were classified according to ejection fraction (EF) into three strata: reduced, EF <40% (HFrEF); mid-range EF 40-49% (HFmrEF); and preserved EF ≥50% (HFpEF). Clinical, echocardiographic, laboratory data and treatment at discharge were recorded and the groups were compared. A multivariable analysis was performed to evaluate the association of EF with outcomes in these three groups. RESULTS: A total of 10.2% of patients had HFmrEF. They were more likely to be men and to have a history of chronic kidney disease and higher levels of NT-proBNP than those with HFpEF. Compared to patients with HFrEF, these patients had less frequently ischaemic aetiology and chronic obstructive pulmonary disease, and a higher proportion of atrial fibrillation and hypertension. In HFmrEF, the use of beta-blockers, aldosterone antagonists and antiplatelet drugs was lower than in HFrEF, but the use of calcium channel blockers and anticoagulants was higher. There were no differences between groups in 30-day and 1-year readmission rates. However, patients with HFrEF had significantly higher 1-year mortality (28%) than patients with HFmrEF and HFpEF (20% and 22%, p<0.001). CONCLUSIONS: Clinical characteristics and treatment among patients with HF differ depending on EF strata. Prognosis of patients with HFmrEF is closer to that of HFpEF, being medium term survival better than in HFrEF.

Type and doses of oral anticoagulants and adherence to anticoagulant treatment in elderly patients with atrial fibrillation: the ESPARTA study.

AIM: To analyze the use of oral anticoagulants in elderly patients with atrial fibrillation in clinical practice. PATIENTS & METHODS: Cross-sectional and multicenter study performed in atrial fibrillation patients ≥75 years treated with oral anticoagulants ≥3 months. RESULTS: 837 patients (83.0 ± 5.0 years; CHA2DS2-VASc 5.0 ± 1.4; HAS-BLED 2.1 ± 0.9; 70.8% vitamin K antagonists; 29.2% direct oral anticoagulants [DOACs]) were included. Poor adherence was observed in 27.9% of patients. Higher scores in the Pfeiffer's test and FRAIL scale were associated with poorer adherence. Among patients treated with DOACs, 62.3% received the lower doses. Having high CHADS2 score and being older were associated with the use of low doses. CONCLUSION: 28% of patients had a poor adherence to anticoagulant treatment. 62% of patients were treated with the lower doses of DOACs.

High serum osmolarity at admission determines a worse outcome in patients with heart failure: Is a new target emerging?

AIMS: The osmolarity of human serum is restricted to a tightly regulated range, and any deviation has clinical implications. Our aim in this study was to establish whether differences in serum osmolarity in heart failure (HF) patients are related with a worse outcome. METHODS: We evaluated the prognostic value of serum osmolarity in patients with HF from the Spanish National Registry on Heart Failure (RICA), a multicenter, prospective registry that enrolls patients admitted for decompensated HF and follows them for 1year. Patients were divided into quartiles according to osmolarity levels. Primary endpoint was the combination of all-cause mortality and hospital readmissions for HF. RESULTS: A total of 2568 patients (47.46% men) were included. Patients with higher osmolarity were older, presented more comorbidities (especially diabetes mellitus and chronic kidney disease), and consequently had higher levels of glucose, urea, creatinine and potassium. During the 1-year follow-up, mortality among the quartiles was 18% (Q1), 18% (Q2), 23% (Q3) and 28% (Q4), p<0.001. After adjusting for baseline characteristics, high serum osmolarity was significantly associated with all-cause mortality (RR 1.02, 95% CI 1.01-1.03, p<0.001). We also found a significant increase in the combined endpoint of mortality and readmission among quartiles with higher osmolarity (p<0.001). Diabetes, eGFR, Barthel index, systolic blood pressure, body mass index, hemoglobin, NYHA class and beta-blocking agents were also independently associated with the primary endpoint. CONCLUSIONS: In patients admitted for decompensated HF, high serum osmolarity predicts a worse outcome, and is associated with a higher comorbidity burden, supporting its use as a candidate prognostic target in HF.

Influencia del grado de anemia en el pronóstico de los pacientes de edad avanzada con insuficiencia cardíaca (Estudio SPAN-HF) / Influence of the degree of anaemia on the prognosis of older adults with heart failure (SPAN-HF study)

Objetivo:Evaluar si un valor óptimo de hemoglobina sostenido en los 3 meses posteriores al ingreso por descompensación de insuficiencia cardíaca (IC) reduce la morbimortalidad durante los 12 meses posteriores a un ingreso por IC aguda.Pacientes y método:Estudio retrospectivo de los 1408 pacientes mayores de 65 años incluidos en el registro RICA divididos en 3 grupos: sin anemia (grupo A), anemia recuperada (grupo B) y anemia persistente (grupo C), según los niveles de hemoglobina en el ingreso y a los 3 meses tras el alta. Se construyeron curvas de Kaplan-Meier, comparando los grupos mediante la prueba de log-rank y se realizó un modelo de regresión de Cox para analizar la supervivencia.Resultados:Se incluyeron 578 (41,1%), 299 (21,2%) y 531 (37,7%) en los grupos A, B y C, respectivamente. Registramos un total de 768 muertes y reingresos. Hubo 23 (4%), 12 (4%) y 49 (9,2%) (p=0,001) individuos que fallecieron debido a la IC, y 154 (27%), 73 (24%) y 193 (36%) (p<0,001) reingresaron por esta patología, respectivamente. Los pacientes con anemia persistente tuvieron un riesgo superior de fallecimiento (RR: 1,29; IC95% de 1,04-1,61; p=0,024) o reingreso (1,92; IC95% de 1,16-3,19; p=0,012) por IC.Conclusiones:La anemia persistente en los meses posteriores a un ingreso por IC aumenta la morbimortalidad en el año posterior.

Objective:To assess whether a sustained optimal haemoglobin value in the 3 months after admission for heart failure (HF) decompensation reduces morbidity and mortality during the 12 months after admission for acute HF.Patients and method:Retrospective study of the 1408 patients older than 65 years included in the RICA registry divided into 3 groups: no anaemia (group A), recovered anaemia (group B), and persistent anaemia (group C), according to haemoglobin levels on admission, and 3 months after discharge. Kaplan-Meier curves were constructed, comparing the groups using the log-rank test and a Cox regression model was performed to analyse survival.Results:578 (41.1%), 299 (21.2%) and 531 (37.7%) were included in groups A, B and C, respectively. We recorded a total of 768 deaths and readmissions. There were 23 (4%), 12 (4%) and 49 (9.2%), (p=.001) individuals who died due to HF and 154 (27%), 73 (24%) and 193 (36%) (P<.001) admissions for this pathology, respectively. Patients with persistent anaemia had a higher risk of death (RR 1.29, 95% CI 1.04-1.61, P=.024) or readmission (1.92, 95% CI 1.16-3, 19; P=.012) due to HF.Conclusions:Persistent anaemia in the months after admission for HF increases morbidity and mortality in the subsequent year. (AU)