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Chronic kidney disease (CKD) as identified by a reduced estimated glomerular filtration rate (eGFR) is a common comorbidity in patients with heart failure with reduced ejection fraction (HFrEF). The presence of CKD is associated with more severe heart failure, and CKD itself is a strong independent risk factor of poor cardiovascular outcome. Furthermore, the presence of CKD often influences the decision to start, uptitrate, or discontinue possible life-saving HFrEF therapies. Because pivotal HFrEF randomized clinical trials have historically excluded patients with stage 4 and 5 CKD (eGFR <30 mL/min/1.73 m2), information on the efficacy and tolerability of HFrEF therapies in these patients is limited. However, more recent HFrEF trials with novel classes of drugs included patients with more severe CKD. In this review on medical therapy in patients with HFrEF and CKD, we show that for both all-cause mortality and the combined end point of cardiovascular death or heart failure hospitalization, most drug classes are safe and effective up to CKD stage 3B (eGFR minimum 30 mL/min/1.73 m2). For more severe CKD (stage 4), there is evidence of safety and efficacy of sodium glucose cotransporter 2 inhibitors, and to a lesser extent, angiotensin-converting enzyme inhibitors, vericiguat, digoxin and omecamtiv mecarbil, although this evidence is restricted to improvement of cardiovascular death/heart failure hospitalization. Data are lacking on the safety and efficacy for any HFrEF therapies in CKD stage 5 (eGFR < 15 mL/min/1.73 m2 or dialysis) for either end point. Last, although an initial decline in eGFR is observed on initiation of several HFrEF drug classes (angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers/mineralocorticoid receptor antagonists/angiotensin receptor blocker neprilysin inhibitors/sodium glucose cotransporter 2 inhibitors), renal function often stabilizes over time, and the drugs maintain their clinical efficacy. A decline in eGFR in the context of a stable or improving clinical condition should therefore not be cause for concern and should not lead to discontinuation of life-saving HFrEF therapies.
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Medicina Baseada em Evidências , Insuficiência Cardíaca , Insuficiência Renal Crônica , Intervalo Livre de Doença , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/terapia , Taxa de SobrevidaRESUMO
BACKGROUND: Changes in renal function have been associated with differential outcomes in patients with acute heart failure (HF). However, individual trajectories of changes in renal function are unknown, and it is unclear whether they relate to different clinical characteristics and clinical outcomes. Our aim was to investigate the prognostic importance of individual trajectories of change in renal function in acute HF. METHODS: This was a retrospective, observational analysis from the double-blind, randomized, placebo-controlled PROTECT trial in patients with acute HF. We identified and internally validated 8 different renal trajectories among 1897 patients by visual inspection of inhospital serum creatinine changes. The primary outcome measure was all-cause mortality at 180 days. Mean age was 70 ± 12 years; 70% were male, and mean baseline estimated glomerular filtration rate was 49.0 mL/min/1.73m2. RESULTS: A total of 8 different trajectories was established. The most prevalent trajectories were an inhospital bump (19.0%), a sustained increase (17.6%) and a dip (14.5%) in serum creatinine. Overall, the clinical characteristics of patients in different trajectories were remarkably similar. Crude 180-day mortality rates ranged from 12.0% in the trajectory, with no significant changes to 18.3% in the trajectory of sustained increase without significant differences. Overall, after multivariable adjustment, there was no trajectory of changes in renal function that was associated with significantly better or worse outcomes. CONCLUSIONS: Trajectories of changes in renal function in acute HF differ considerably on the patient level. Despite these differences, clinical characteristics and outcomes were similar, therefore, questioning the prognostic importance of changes in renal function in acute HF.
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Taxa de Filtração Glomerular/fisiologia , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Nefropatias/mortalidade , Nefropatias/fisiopatologia , Rim/fisiologia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Insuficiência Cardíaca/diagnóstico , Humanos , Nefropatias/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida/tendênciasRESUMO
BACKGROUND: The Kidney Disease Improving Global Outcomes (KDIGO) classification integrates both estimated glomerular filtration rate and urine-albumin-creatinine ratio to stratify risk more comprehensively in patients with chronic kidney disease. There are limited data assessing whether this classification system is associated with prognosis and treatment response in heart failure populations. OBJECTIVES: The aim of this study was to evaluate the relative treatment effects of sacubitril/valsartan across the KDIGO risk categories in patients with HFrEF. METHODS: PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) was a global randomized controlled trial evaluating sacubitril/valsartan vs enalapril in patients with heart failure with reduced ejection fraction (HFrEF). Patients were classified according to low, moderate, and high/very high KDIGO risk. Treatment responses were assessed according to baseline KDIGO risk. The primary outcome was a composite of cardiovascular (CV) death or heart failure hospitalization. A renal composite outcome was defined as sustained decline in estimated glomerular filtration rate by ≥40% or end-stage kidney disease. RESULTS: Among 1,910 (23% of total) participants with available data, 42%, 32%, and 26% were classified as low, moderate, and high/very high KDIGO risk, respectively. Patients in the highest KDIGO risk categories experienced the highest rates of the primary composite outcome (7.6 per 100 person-years [95% CI: 6.5-9.0 per 100 person-years], 9.4 per 100 person-years [95% CI: 7.9-11.2 per 100 person-years], and 14.9 per 100 person-years [95% CI: 12.7-17.6 per 100 person-years]; P < 0.001). Sacubitril/valsartan had a similar safety profile and demonstrated consistent effects on the risk of both the primary outcome (PInteraction = 0.31) and the renal composite outcome (PInteraction = 0.50) across the spectrum of KDIGO risk. CONCLUSIONS: One in 4 patients with HFrEF were classified as at least high KDIGO kidney risk; these individuals faced concordantly the highest risks of CV events. Sacubitril/valsartan exhibited consistent CV and kidney protective benefits as well as safety across the spectrum of baseline kidney risk. These data further support initiation of sacubitril/valsartan in HFrEF across a broad range of kidney risk. (This Study Will Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure [PARADIGM-HF]; NCT01035255).
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Aminobutiratos , Antagonistas de Receptores de Angiotensina , Compostos de Bifenilo , Combinação de Medicamentos , Insuficiência Cardíaca , Tetrazóis , Valsartana , Humanos , Aminobutiratos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Masculino , Feminino , Idoso , Tetrazóis/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Pessoa de Meia-Idade , Estudos Prospectivos , Taxa de Filtração Glomerular/efeitos dos fármacos , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Resultado do Tratamento , Volume Sistólico/efeitos dos fármacos , Volume Sistólico/fisiologiaRESUMO
Galectin-3 and Suppression of tumorigenicity-2 (ST2) are known markers of cardiac fibrosis. We investigated the prognostic value of fibrotic markers for the development of diastolic dysfunction and long-term outcome in patients suffering an ST-elevated myocardial infarction (STEMI). We analyzed 236 patients from the GIPS-III cohort with available echocardiographic studies and plasma measurements at hospitalization and after 4 months follow-up. Adjusted logistic mixed effects modelling revealed no association between the occurrence of diastolic dysfunction over time with abnormal plasma levels of galectin-3 and ST2. We observed no differences regarding survival outcome at follow-up of 5 years between patients with normal versus abnormal values in both galectin-3 (P = 0.75), and ST2 (P = 0.85). In conclusion, galectin-3 and sST2 were not associated with the development of diastolic dysfunction in non-diabetic patients that presented with a STEMI.
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Biomarcadores , Diástole , Fibrose , Proteína 1 Semelhante a Receptor de Interleucina-1 , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Biomarcadores/sangue , Proteína 1 Semelhante a Receptor de Interleucina-1/sangue , Idoso , Galectina 3/sangue , Galectinas/sangue , Prognóstico , Ecocardiografia , Seguimentos , Proteínas Sanguíneas/metabolismoRESUMO
AIMS: Acute heart failure (AHF) is associated with end-organ dysfunction. The effect of AHF on the pancreas has not been studied. We aim to evaluate serum markers of pancreatic damage during hospitalization for AHF. METHODS AND RESULTS: In data from the Pragmatic Urinary Sodium-based treatment algoritHm in Acute Heart Failure (PUSH-AHF) study, amylase and lipase values were extracted from available serum samples at baseline, and at 24 and 72 h after hospitalization. The differences between pancreatic enzymes between timepoints were evaluated using the Friedman test. Associations with N-terminal pro-B-type natriuretic peptide (NT-proBNP) were tested using linear regression analysis. The study population consisted of 274 patients. Mean age was 73 ± 11 years, and 117 (43%) were women. Mean left ventricular ejection fraction (LVEF) was 38 ± 14%; 53 (19%) patients had HF with a preserved LVEF (≥50%). At baseline, median amylase and lipase were within normal range (47 [33-63] U/L and 30 [21-44] U/L, respectively). Both enzymes significantly increased in the first 72 h (P-value for trend <0.001); mean change was 9 ± 22 U/L for amylase, and 10 ± 22 U/L for lipase. Moreover, NT-proBNP at baseline showed a positive correlation with mean change in pancreatic enzymes in 72 h (P = 0.02 for amylase and P = 0.006 for lipase). CONCLUSION: Patients admitted for AHF exhibited a significant increase in serum values of pancreatic enzymes in the first 72 h, suggesting that an episode of AHF affects the pancreatic tissue. This rise in pancreatic enzymes was associated with HF severity, as reflected by NT-proBNP.
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AIM: In a randomized controlled trial, we recently showed that a natriuresis-guided diuretic approach improved natriuresis and diuresis in patients with acute heart failure (HF). In this pre-specified analysis, we investigated the association between (worsening) renal function, outcomes and the effect of intensive natriuresis-guided loop diuretic therapy as compared with standard of care. METHODS AND RESULTS: The Pragmatic Urinary Sodium-based algoritHm in Acute Heart Failure (PUSH-AHF) trial randomized patients to natriuresis-guided diuretic therapy or standard of care. Serum creatinine and estimated glomerular filtration rate (eGFR) were assessed at fixed timepoints, and worsening renal function (WRF) was assessed at 72 h. The primary outcome was the interaction between randomized treatment allocation, baseline eGFR and the dual primary outcome of PUSH-AHF: total natriuresis at 24 h and time to all-cause mortality or HF rehospitalization at 180 days. In 309 patients, median baseline eGFR was 53 (35-73) ml/min/1.73 m2, and 58% had eGFR <60 ml/min/1.73 m2. Baseline eGFR did not significantly modify the treatment effect of natriuresis-guided diuretic therapy on natriuresis at 24 h (p for interaction = 0.730). However, baseline eGFR significantly modified the effect on all-cause mortality and HF rehospitalization (p for interaction = 0.017): the risk of this second primary outcome was lower in patients with lower eGFR who were randomized to the natriuresis-guided group. In the natriuresis-guided arm, eGFR decreased more (-11.0 vs. -6.91 ml/min/1.73 m2; p = 0.002) during the first 3 days, but this effect was attenuated at discharge (-10.3 vs. -8.69 ml/min/1.73 m2; p = 0.38). WRF was more frequently observed in patients randomized to natriuresis-guided treatment, but was not associated with worse clinical outcomes. CONCLUSIONS: Natriuresis-guided diuretic treatment improved diuresis and natriuresis irrespective of baseline eGFR and occurrence of WRF, was effective even in patients with low eGFR, and the observed effect on eGFR was transient and not associated with worse clinical outcomes.
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Taxa de Filtração Glomerular , Insuficiência Cardíaca , Natriurese , Humanos , Feminino , Masculino , Taxa de Filtração Glomerular/efeitos dos fármacos , Taxa de Filtração Glomerular/fisiologia , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Idoso , Natriurese/efeitos dos fármacos , Pessoa de Meia-Idade , Diuréticos/uso terapêutico , Diuréticos/administração & dosagem , Inibidores de Simportadores de Cloreto de Sódio e Potássio/uso terapêutico , Inibidores de Simportadores de Cloreto de Sódio e Potássio/administração & dosagem , Resultado do Tratamento , Doença Aguda , Creatinina/sangueRESUMO
BACKGROUND: Multimorbidity frequently occurs in patients with acute heart failure (AHF). The co-occurrence of comorbidities often follows specific patterns. OBJECTIVES: This study investigated multimorbidity subtypes and their associations with clinical outcomes. METHODS: From the prospective RELAX-AHF-2 (Relaxin for the Treatment of Acute Heart Failure-2) trial, 6,545 patients (26% with HF with preserved ejection fraction, defined as LVEF ≥50%) were classified into multimorbidity groups using latent class analysis. The association between subgroups and clinical outcomes was examined. Validation of these findings was conducted in the RELAX-AHF trial, which comprised 1,161 patients. RESULTS: Five distinct multimorbidity groups emerged: 1) diabetes and chronic kidney disease (CKD) (often male, high prevalence of CKD and diabetes mellitus); 2) ischemic (ischemic HF); 3) elderly/atrial fibrillation (AF) (oldest, high prevalence of AF); 4) metabolic (obese, hypertensive, more often HF with preserved ejection fraction); and 5) young (fewest comorbidities). After adjusting for confounders, patients in the diabetes and CKD (HR: 1.80; 95% CI: 1.50-2.20), elderly/AF (HR: 1.42; 95% CI: 1.20-1.70), and metabolic (HR: 1.40; 95% CI: 1.20-1.80) groups had higher rates of the composite outcome than patients in the young group, primarily driven by differences in rehospitalization. Treatment allocation (placebo or serelaxin) modified these associations (Pinteraction <0.001). Serelaxin-treated patients in the young group were associated with a lower risk for all-cause mortality (HR: 0.59; 95% CI: 0.40-0.90). Similarly, patients from the RELAX-AHF trial clustered in 5 multimorbidity groups. The clinical characteristics and associations with outcomes could also be validated. CONCLUSIONS: Comorbidities naturally clustered into 5 mutually exclusive groups in RELAX-AHF-2, showing variations in clinical outcomes. These data emphasize that the specific combination of comorbidities can influence adverse outcomes and treatment responses in patients with AHF.
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BACKGROUND: Sacubitril/valsartan is a foundational therapy for patients with heart failure. Although current U.S. Food and Drug Administration labeling does not provide guidance regarding initiation or continuation of sacubitril/valsartan in patients with worsening kidney function, guidelines identify estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 as a contraindication to therapy. OBJECTIVES: This study aims to assess the safety and efficacy of continuing sacubitril/valsartan in patients with deterioration of kidney function below an eGFR of 30 mL/min/1.73 m2. METHODS: The association between a deterioration in eGFR <30 mL/min/1.73 m2, efficacy and safety outcomes, and treatment with sacubitril/valsartan vs renin-angiotensin system inhibitor were evaluated using time updated Cox models in a post hoc parallel trial analyses of PARADIGM-HF and PARAGON-HF. RESULTS: Among 8,346 randomized patients in PARADIGM-HF and 4,746 in PARAGON-HF, 691 (8.3%) and 613 (12.9%), respectively, had an eGFR <30 mL/min/1.73 m2 at least once in follow-up. Patients experiencing such deterioration were at higher risk of the primary outcome in both PARADIGM-HF and PARAGON-HF. However, the incidence of the primary outcome remained lower with sacubitril/valsartan vs renin-angiotensin system inhibitor, regardless of deterioration in kidney function in both PARADIGM-HF (Pinteraction = 0.50) and PARAGON-HF (Pinteraction = 0.64). Rates of key safety outcomes were higher among patients experiencing eGFR deterioration; however, rates were similar between treatment groups including among those who remained on treatment. CONCLUSIONS: Patients experiencing deterioration of kidney function to a value below eGFR 30 mL/min/1.73 m2 faced high risk of cardiovascular and kidney disease outcomes. Continuation of sacubitril/valsartan was associated with persistent clinical benefit and no incremental safety risk. These data support continuation of sacubitril/valsartan for heart failure treatment even when eGFR declines below this threshold (PARADIGM-HF [Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure], NCT01035255; and PARAGON-HF [Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction], NCT01920711).
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AIMS: Heart failure (HF) guidelines recommend initiation and optimization of guideline-directed medical therapy, including mineralocorticoid receptor antagonists (MRAs), before hospital discharge. However, scientific evidence for this recommendation is lacking. Our objective was to determine whether initiation of MRA prior to hospital discharge is associated with improved outcomes. METHODS AND RESULTS: We performed a secondary analysis of 6197 patients enrolled in the RELAX-AHF-2 study. Patients were divided into four groups according to MRA therapy at baseline and discharge. At baseline 30% of patients received MRA therapy, which increased to 50% of patients at discharge. In-hospital initiation of an MRA was observed in 1690 (27%) patients, 1438 (23%) patients remained on MRA therapy, 418 (7%) patients discontinued MRA treatment, and 2651 (43%) patients did not receive an MRA during hospital stay. Compared with patients who did not receive MRA therapy, in-hospital initiation of an MRA was independently associated with lower risks of mortality (multivariable hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.60-0.96; p = 0.02), cardiovascular death (HR 0.77, 95% CI 0.59-1.01; p = 0.06), hospitalization for HF or renal failure (HR 0.72, 95% CI 0.60-0.86; p = 0.0003) and the composite endpoint of cardiovascular death and/or rehospitalization for HF or renal failure (HR 0.71, 95% CI 0.61-0.83; p < 0.0001) at 180 days. These results were independent of baseline left ventricular ejection fraction. CONCLUSION: In patients hospitalized for acute HF, in-hospital initiation of an MRA was associated with improved post-discharge outcomes, independent of left ventricular ejection fraction and other potential confounders.
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Insuficiência Cardíaca , Insuficiência Renal , Humanos , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Volume Sistólico , Resultado do Tratamento , Função Ventricular Esquerda , Assistência ao Convalescente , Alta do Paciente , HospitalizaçãoRESUMO
Measurement of natriuresis has been suggested as a reliable, easily obtainable biomarker for assessment of the response to diuretic treatment in patients with acute heart failure (AHF). Here, to assess whether natriuresis-guided diuretic therapy in patients with AHF improves natriuresis and clinical outcomes, we conducted the pragmatic, open-label Pragmatic Urinary Sodium-based algoritHm in Acute Heart Failure trial, in which 310 patients (45% female) with AHF requiring treatment with intravenous loop diuretics were randomly assigned to natriuresis-guided therapy or standard of care (SOC). In the natriuresis-guided arm, natriuresis was determined at set timepoints, prompting treatment intensification if spot urinary sodium levels were <70 mmol l-1. The dual primary endpoints were 24 h urinary sodium excretion and a combined endpoint of time to all-cause mortality or adjudicated heart failure rehospitalization at 180 days. The first primary endpoint was met, as natriuresis in the natriuresis-guided and SOC arms was 409 ± 178 mmol arm versus 345 ± 202 mmol, respectively (P = 0.0061). However, there were no significant differences between the two arms for the combined endpoint of time to all-cause mortality or first heart failure rehospitalization, which occurred in 46 (31%) and 50 (31%) of patients in the natriuresis-guided and SOC arms, respectively (hazard ratio 0.92 [95% confidence interval 0.62-1.38], P = 0.6980). These findings suggest that natriuresis-guided therapy could be a first step towards personalized treatment of AHF. ClinicalTrials.gov registration: NCT04606927 .
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Insuficiência Cardíaca , Natriurese , Feminino , Humanos , Masculino , Doença Aguda , Diuréticos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Sódio/urina , Inibidores de Simportadores de Cloreto de Sódio e Potássio/uso terapêuticoRESUMO
AIMS: The impact of mitral regurgitation (MR) in patients hospitalized for acute heart failure (AHF) is not well established. We assessed the role of MR in patients enrolled in the Relaxin in Acute Heart Failure 2 (RELAX-AHF-2) trial. METHODS AND RESULTS: Patients enrolled in RELAX-AHF-2 with available data regarding MR status were included in this analysis. Baseline characteristics, in-hospital data, and clinical outcomes through 180-day follow-up were evaluated. The impact of moderate/severe MR was assessed. Among 6420 AHF patients with known MR status, 1810 patients (28.2%) had moderate/severe MR. Compared to patients with no/mild MR, those with moderate/severe MR were more likely to have history of heart failure (HF), prior HF hospitalization, more comorbidities, symptoms/signs of HF, lower left ventricular ejection fraction and higher N-terminal pro-B-type natriuretic peptide levels. Moderate/severe MR was associated with longer length of hospital stay, higher rates of residual dyspnoea, increased jugular venous pressure through the index hospitalization and a higher unadjusted risk of the composite of cardiovascular (CV) death or rehospitalization for HF/renal failure (RF) through 180 days (crude hazard ratio [HR] 1.15, 95% confidence interval [CI] 1.03-1.27, p = 0.01). The association between moderate/severe MR and poorer outcomes was not maintained in a multivariable model including several covariates of interest (adjusted HR 1.03, 95% CI 0.91-1.17, p = 0.65). Similar findings were observed for HF/RF rehospitalization alone. CONCLUSIONS: In patients with AHF, moderate/severe MR was associated with a worse clinical profile but did not have an independent prognostic impact on clinical outcomes.
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Insuficiência Cardíaca , Insuficiência da Valva Mitral , Humanos , Doença Aguda , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Hospitalização , Insuficiência da Valva Mitral/complicações , Volume Sistólico , Função Ventricular EsquerdaRESUMO
AIMS: Insufficient diuretic response frequently occurs in patients admitted for acute heart failure (HF) and is associated with worse clinical outcomes. Recent studies have shown that measuring natriuresis early after hospital admission could reliably identify patients with a poor diuretic response during hospitalization who might require enhanced diuretic treatment. This study will test the hypothesis that natriuresis-guided therapy in patients with acute HF improves natriuresis and clinical outcomes. METHODS: The Pragmatic Urinary Sodium-based treatment algoritHm in Acute Heart Failure (PUSH-AHF) is a pragmatic, single-centre, randomized, controlled, open-label study, aiming to recruit 310 acute HF patients requiring treatment with intravenous loop diuretics. Patients will be randomized to natriuresis-guided therapy or standard of care. Natriuresis will be determined at set time points after initiation of intravenous loop diuretics, and treatment will be adjusted based on the urinary sodium levels in the natriuresis-guided group using a pre-specified stepwise approach of increasing doses of loop diuretics and the initiation of combination diuretic therapy. The co-primary endpoint is 24-h urinary sodium excretion after start of loop diuretic therapy and a combined endpoint of all-cause mortality or first HF rehospitalization at 6 months. Secondary endpoints include 48- and 72-h sodium excretion, length of hospital stay, and percentage change in N-terminal pro brain natriuretic peptide at 48 and 72 h. CONCLUSION: The PUSH-AHF study will investigate whether natriuresis-guided therapy, using a pre-specified stepwise diuretic treatment approach, improves natriuresis and clinical outcomes in patients with acute HF.
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Insuficiência Cardíaca , Natriurese , Algoritmos , Diuréticos/uso terapêutico , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Sódio/urina , Inibidores de Simportadores de Cloreto de Sódio e Potássio/uso terapêuticoRESUMO
AIMS: Worsening renal function may impact long-term outcomes in heart failure (HF). However, little is known about the longitudinal trajectories in renal function in relation to HF hospitalization or how this high-risk clinical event impacts renal outcomes. METHODS AND RESULTS: In PARAGON-HF, we evaluated the association between recency of prior HF hospitalization (occurring pre-randomization) and subsequent first renal composite outcome: (i) time to ≥50% decline in estimated glomerular filtration rate (eGFR); (ii) development of end-stage renal disease; or (iii) death attributable to renal causes. A total of 2306 (48.1%) patients had a history of prior HF hospitalization. Incident rates of the renal outcome were highest in those most recently hospitalized and decreased with longer time from last hospitalization. Treatment effect on the renal outcome of sacubitril/valsartan versus valsartan was similar between patients with (hazard ratio [HR] 0.43; 95% confidence interval [CI] 0.24-0.76) and without (HR 0.63; 95% CI: 0.33-1.18; pinteraction = 0.39) a prior history of HF hospitalization and appeared consistent regardless of timing of prior hospitalization for HF (pinteraction = 0.39). Serial eGFR measurements leading up to and after a HF hospitalization (occurring during the study period) and estimated eGFR trajectories using repeated measures regression models with restricted cubic splines were also examined. Patients experiencing a post-randomization HF hospitalization had a significant decline in eGFR prior to hospitalization while patients without HF hospitalization experienced a relatively stable eGFR trajectory (p < 0.001). A change in the rate of decline of eGFR trajectory was observed 12 months preceding a HF hospitalization, and continued in the post-discharge window to 12 months following hospitalization. CONCLUSIONS: Heart failure hospitalization denotes increased risk for kidney disease progression which continues following recovery from HF decompensation in patients with HF with preserved ejection fraction. CLINICAL TRIAL REGISTRATION: PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction), ClinicalTrials.gov NCT01920711.
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Insuficiência Cardíaca , Humanos , Volume Sistólico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/induzido quimicamente , Antagonistas de Receptores de Angiotensina/uso terapêutico , Assistência ao Convalescente , Tetrazóis/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Alta do Paciente , Aminobutiratos/uso terapêutico , Valsartana/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Hospitalização , Combinação de Medicamentos , Rim/fisiologiaRESUMO
PURPOSE: Cognitive biases and factors affecting decision making in critical care can potentially lead to life-threatening errors. We aimed to examine the existing evidence on the influence of cognitive biases and factors on decision making in critical care. MATERIALS AND METHODS: We conducted a scoping review by searching MEDLINE for articles from 2004 to November 2020. We included studies conducted in physicians that described cognitive biases or factors associated with decision making. During the study process we decided on the method to summarize the evidence, and based on the obtained studies a descriptive summary of findings was the best fit. RESULTS: Thirty heterogenous studies were included. Four main biases or factors were observed, e.g. cognitive biases, personal factors, environmental factors, and patient factors. Six (20%) studies reported biases associated with decision making comprising omission-, status quo-, implicit-, explicit-, outcome-, and overconfidence bias. Nineteen (63%) studies described personal factors, twenty-two (73%) studies described environmental factors, and sixteen (53%) studies described patient factors. CONCLUSIONS: The current evidence on cognitive biases and factors is heterogenous, but shows they influence clinical decision. Future studies should investigate the prevalence of cognitive biases and factors in clinical practice and their impact on clinical outcomes.
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Médicos , Viés , Cognição , Cuidados Críticos , Tomada de Decisões , HumanosRESUMO
BACKGROUND: Treatment of heart failure with preserved ejection fraction (HFpEF) with spironolactone is associated with lower risk of heart failure hospitalization (HFH) but increased risk of worsening renal function (WRF). The prognostic implications of spironolactone-associated WRF in HFpEF patients are not well understood. OBJECTIVES: The purpose of this study was to investigate the association between WRF, spironolactone treatment, and clinical outcomes in patients with HFpEF. METHODS: In 1,767 patients randomized to spironolactone or placebo in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial)-Americas study, we examined the incidence of WRF (doubling of serum creatinine) by treatment assignment. Associations between incident WRF and subsequent risk for the primary study endpoint of cardiovascular (CV) death, HFH, or aborted cardiac arrest and key secondary outcomes, including CV death, HFH, and all-cause mortality according to treatment assignment, were examined in time-updated Cox proportional hazards models with an interaction term. RESULTS: WRF developed in 260 (14.7%) patients with higher rates in those assigned to spironolactone compared to placebo (17.8% vs. 11.6%; odds ratio: 1.66; 95% confidence interval: 1.27 to 2.17; p < 0.001). Regardless of treatment, incident WRF was associated with increased risk for the primary endpoint (hazard ratio: 2.04; 95% confidence interval: 1.52 to 2.72; p < 0.001) after multivariable adjustment. Although there was no statistical interaction between treatment assignment and WRF regarding the primary endpoint (interaction p = 0.11), spironolactone-associated WRF was associated with lower risk of CV death (interaction p = 0.003) and all-cause mortality (interaction p = 0.001) compared with placebo-associated WRF. CONCLUSIONS: Among HFpEF patients enrolled in TOPCAT-Americas, spironolactone increased risk of WRF compared with placebo. Rates of CV death were lower with spironolactone in both patients with and without WRF.
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Insuficiência Cardíaca/tratamento farmacológico , Nefropatias/tratamento farmacológico , Rim/efeitos dos fármacos , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Espironolactona/uso terapêutico , Volume Sistólico/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Seguimentos , Taxa de Filtração Glomerular/efeitos dos fármacos , Taxa de Filtração Glomerular/fisiologia , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Rim/fisiologia , Nefropatias/epidemiologia , Nefropatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Espironolactona/farmacologia , Volume Sistólico/fisiologiaRESUMO
OBJECTIVES: This study investigated the association between baseline renal function and the net benefit of spironolactone in patients with heart failure (HF) with a preserved ejection fraction (HFpEF). BACKGROUND: Guidelines recommend consideration of spironolactone to reduce HF hospitalization in HFpEF. However, spironolactone may increase risk for hyperkalemia and worsening renal function, particularly in patients with chronic kidney disease. METHODS: This investigation analyzed data from patients enrolled in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial) Americas study (N = 1,767) to examine the association between the baseline estimated glomerular filtration rate (eGFR) and the primary composite outcome of cardiovascular death, HF hospitalization, or aborted cardiac arrest, as well as safety outcomes, including hyperkalemia, worsening renal function, and permanent drug discontinuation for adverse events (AEs). Variations in the efficacy and safety of spironolactone according to eGFR were examined in Cox models using interaction terms. RESULTS: The incidence of both the primary outcome and drug-related AEs increased with declining eGFR. Compared with placebo, across all eGFR categories, spironolactone was associated with lower relative risk for the primary efficacy outcome and for hypokalemia, but higher relative risk for hyperkalemia, worsening renal function, and drug discontinuation. During 4-year follow-up, the absolute risk for AEs that prompted drug discontinuation was amplified in the lower eGFR categories, which suggested heightened risk for drug intolerance with declining renal function. CONCLUSIONS: Although consistent efficacy of spironolactone was observed across the range of eGFR, the risk of AEs was amplified in the lower eGFR categories. These data supported use of spironolactone to treat HFpEF patients with advanced chronic kidney disease only when close laboratory surveillance is possible.
Assuntos
Taxa de Filtração Glomerular , Insuficiência Cardíaca/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Insuficiência Renal Crônica/metabolismo , Espironolactona/uso terapêutico , Volume Sistólico , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/mortalidade , Comorbidade , Desprescrições , Progressão da Doença , Feminino , Parada Cardíaca/epidemiologia , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Hospitalização/estatística & dados numéricos , Humanos , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/epidemiologia , Hipopotassemia/induzido quimicamente , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Insuficiência Renal Crônica/epidemiologia , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Levels of cTn (cardiac troponin) are frequently elevated in patients with heart failure (HF) and reduced ejection fraction (EF) and correlate with the risk for mortality. However, factors associated with high cTn concentrations and the association with cardiovascular events in patients with HF and preserved EF are unclear. METHODS AND RESULTS: Of 1767 subjects with symptomatic HF with preserved EF from the Americas part of the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial), 236 underwent baseline measurements of high-sensitivity (hs) cTnI using the Abbott Architect STAT assay. Baseline factors correlated with hs-cTnI levels were assessed in stepwise linear regression models and the association between hs-cTnI and adjudicated study outcomes was examined in Cox models. The median hs-cTnI concentration at baseline was 6.3 ng/L (interquartile range, 3.4-12.9 ng/L) with levels detectable in 99.2% of patients. Higher hs-cTnI concentrations were associated with male sex, black race, lower estimated glomerular filtration rate and higher NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels. After multivariable adjustment, higher concentrations of hs-cTnI were associated with greater risk for the composite of cardiovascular death or HF hospitalization (69 events during mean follow-up 2.6±1.5 years): hazard ratio 1.42 (95% CI, 1.20-1.69), P<0.001 per doubling of hs-cTnI. Compared with those in the lowest quartile of hs-cTnI, patients in the highest quartile demonstrated a nearly 5-fold higher risk of cardiovascular death and HF hospitalization (hazard ratio 4.85 [1.99-11.83], P=0.001). There was no interaction between hs-cTnI and spironolactone treatment with regard to the primary composite end point (interaction P=0.94). CONCLUSIONS: In ambulatory patients with HF with preserved EF, levels of hs-cTnI are higher in male patients with black race, lower estimated glomerular filtration rate, and higher NT-proBNP. As in those with HF and reduced EF, higher hs-cTnI levels are independently associated with risk for cardiovascular death and HF hospitalization. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00094302.