The administration of loop diuretics to achieve decongestion is the cornerstone of therapy for acute heart failure. Unfortunately, impaired response to diuretics is common in these patients and ...associated with adverse outcomes. Diuretic resistance is thought to result from a complex interplay between cardiac and renal dysfunction, and specific renal adaptation and escape mechanisms, such as neurohormonal activation and the braking phenomenon. However, our understanding of diuretic response in patients with acute heart failure is still limited and a uniform definition is lacking. Three objective methods to evaluate diuretic response have been introduced, which all suggest that diuretic response should be determined based on the effect of diuretic dose administered. Several strategies have been proposed to overcome diuretic resistance, including combination therapy and ultrafiltration, but prospective studies in patients who are truly unresponsive to diuretics are lacking. An enhanced understanding of diuretic response should ultimately lead to an improved, individualized approach to treating patients with acute heart failure.
Aim
Diminished diuretic response is common in patients with acute heart failure, although a clinically useful definition is lacking. Our aim was to investigate a practical, workable metric for ...diuretic response, examine associated patient characteristics and relationships with outcome.
Methods and results
We examined diuretic response (defined as Δ weight kg/40 mg furosemide) in 1745 hospitalized acute heart failure patients from the PROTECT trial. Day 4 response was used to allow maximum differentiation in responsiveness and tailoring of diuretic doses to clinical response, following sensitivity analyses. We investigated predictors of diuretic response and relationships with outcome. The median diuretic response was −0.38 (−0.80 to −0.13) kg/40 mg furosemide. Poor diuretic response was independently associated with low systolic blood pressure, high blood urea nitrogen, diabetes, and atherosclerotic disease (all P < 0.05). Worse diuretic response independently predicted 180-day mortality (HR: 1.42; 95% CI: 1.11–1.81, P = 0.005), 60-day death or renal or cardiovascular rehospitalization (HR: 1.34; 95% CI: 1.14–1.59, P < 0.001) and 60-day HF rehospitalization (HR: 1.57; 95% CI: 1.24–2.01, P < 0.001) in multivariable models. The proposed metric—weight loss indexed to diuretic dose—better captures a dose–response relationship. Model diagnostics showed diuretic response provided essentially the same or slightly better prognostic information compared with its individual components (weight loss and diuretic dose) in this population, while providing a less biased, more easily interpreted signal.
Conclusions
Worse diuretic response was associated with more advanced heart failure, renal impairment, diabetes, atherosclerotic disease and in-hospital worsening heart failure, and predicts mortality and heart failure rehospitalization in this post hoc, hypothesis-generating study.
Chronic kidney disease (CKD) and worsening renal function (WRF) have been associated with poor outcome in heart failure (HF).
Articles were identified by literature search of MEDLINE (from inception ...to 1 July 2012) and Cochrane. We included studies on HF patients and mortality risk with CKD and/or WRF. In a secondary analysis, we selected studies investigating predictors of WRF. We retrieved 57 studies (1,076,104 patients) that investigated CKD and 28 studies (49,890 patients) that investigated WRF. The prevalence of CKD was 32% and associated with all-cause mortality: odds ratio (OR) 2.34, 95% confidence interval (CI) 2.20-2.50, P < 0.001). Worsening renal function was present in 23% and associated with unfavourable outcome (OR 1.81, 95% CI 1.55-2.12, P < 0.001). In multivariate analysis, moderate renal impairment: hazard ratio (HR) 1.59, 95% CI 1.49-1.69, P < 0.001, severe renal impairment, HR 2.17, 95% CI 1.95-2.40, P < 0.001, and WRF, HR 1.95, 95% CI 1.45-2.62, P < 0.001 were all independent predictors of mortality. Across studies, baseline CKD, history of hypertension and diabetes, age, and diuretic use were significant predictors for the occurrence of WRF.
Across all subgroups of patients with HF, CKD, and WRF are prevalent and associated with a strongly increased mortality risk, especially CKD. Specific conditions may predict the occurrence of WRF and thereby poor prognosis.
Background Diuretic unresponsiveness often occurs during hospital admission for acute heart failure (AHF) and is associated with adverse outcome. This study aims to investigate determinants, clinical ...outcome, and the effects of nesiritide on diuretic response early after admission for AHF. Methods Diuretic response , defined as weight loss per 40 mg of furosemide or equivalent, was examined from hospital admission to 48 hours in 4,379 patients from the ASCEND-HF trial. As an additional analysis, a urinary diuretic response metric was investigated in 5,268 patients using urine volume from hospital admission to 24 hours per 40 mg of furosemide or equivalent. Results Mean diuretic response was −0.42 kg/40 mg of furosemide (interquartile range −1.0, −0.05). Poor responders had lower blood pressure, more frequent diabetes, long-term use of loop diuretics, poorer baseline renal function, and lower urine output (all P < .01). Randomized nesiritide treatment was not associated with diuretic response ( P = .987). Good diuretic response was independently associated with a significantly decreased risk of 30-day all-cause mortality or heart failure rehospitalization (odds ratio 0.44, 95% CI 0.29-0.65, highest vs lowest quintile, P < .001). Diuretic response based on urine output per 40 mg of furosemide showed similar results in terms of clinical predictors, association with outcome, and the absence of an effect of nesiritide. Conclusions Poor diuretic response early after hospital admission for AHF is associated with low blood pressure, renal impairment, low urine output, and an increased risk of death or rehospitalization early after discharge. Nesiritide had a neutral effect on diuretic response.
Surgical clip closure of the left atrial appendage Rosati, Fabrizio; Maat, Gijs E.; Valente, Mattia A. E. ...
Journal of cardiovascular electrophysiology,
October 2021, Letnik:
32, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Atrial fibrillation (AF) is the most common atrial arrhythmia, but it is not a benign disease. AF is an important risk factor for thromboembolic events, causing significant morbidity and mortality. ...The left atrial appendage (LAA) plays an important role in thrombus formation, but the ideal management of the LAA remains a topic of debate. The increasing popularity of surgical epicardial ablation and hybrid endoepicardial ablation approaches, especially in patients with a more advanced diseased substrate, has increased interest in epicardial LAA management. Minimally invasive treatment options for the LAA offer a unique opportunity to close the LAA with a clip device. This review highlights morphologic, electrophysiologic, and surgical aspects of the LAA with regard to AF surgery, and aims to illustrate the importance of surgical clip closure of the LAA.
Aims
Episodes of acute heart failure (AHF) unfavourably affect multiple organs, which may have an adverse impact on the outcomes. We investigated the prevalence and clinical consequences of abnormal ...liver function tests (LFTs) in AHF patients enrolled in the PROTECT study.
Methods and results
The LFTs comprised serial assessment of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and albumin at baseline and during follow‐up (daily until discharge, on days 7 and 14). The prevalence of abnormal LFTs (above upper limit of normal for AST and ALT or below lower limit of normal for albumin) was: at baseline AST 20%, ALT 12%, albumin 40%; and at day 14: AST 15%, ALT 9%, albumin 26%. Abnormal LFTs at baseline were associated with a higher risk of in‐hospital death with odds ratios 95% confidence interval (CI) of 3.5 (1.7–7.3) for AST, 3.9 (1.8–8.4) for ALT, and 2.8 (1.3–5.9) for albumin (all P < 0.01). Abnormal baseline and discharge LFTs had an unfavourable impact on 180‐day mortality with hazard ratios (95% CI) for baseline AST, ALT, and albumin of 1.3 (1.0–1.7), 1.1 (1.0–1.2), 1.4 (1.1–1.8), respectively, and 1.5 (1.1–2.0), 1.5 (1.0–2.2), and 1.6 (1.2–2.1), for discharge AST, ALT, albumin, respectively (all P < 0.05). Analysis of LFTs trajectories (calculated as changes in LFTs over time) revealed that increasing AST and ALT on day 3 as well as decreasing albumin on day 4 were independent prognosticators of 180‐day outcome (all P < 0.05).
Conclusions
Abnormal LFTs are frequent in AHF at baseline and during hospital stay and predict worse outcomes. Whether this association is causal and what are the underlying mechanisms involved require further study.
The aim of this study was to evaluate the ability of Neutrophil Gelatinase-Associated Lipocalin (NGAL) to predict clinically relevant worsening renal function (WRF) in acute heart failure (AHF). ...Plasma NGAL and serum creatinine changes during the first 4 days of admission were investigated in 1447 patients hospitalized for AHF and enrolled in the Placebo-Controlled Randomized Study of the Selective A₁Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized with Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function (PROTECT) study. WRF was defined as serum creatinine rise ≥ 0.3 mg/dL through day 4. Biomarker patterns were described using linear mixed models. WRF developed in 325 patients (22%). Plasma NGAL did not rise earlier than creatinine in patients with WRF. After multivariable adjustment, baseline plasma NGAL, but not creatinine, predicted WRF. AUCs for WRF prediction were modest (<0.60) for all models. NGAL did not independently predict death or rehospitalization (
= n.s.). Patients with WRF and high baseline plasma NGAL had a greater risk of death, and renal or cardiovascular rehospitalization by 60 days than patients with WRF and a low baseline plasma NGAL (p for interaction = 0.024). A rise in plasma NGAL after baseline was associated with a worse outcome in patients with WRF, but not in patients without WRF (
= 0.007). On the basis of these results, plasma NGAL does not provide additional, clinically relevant information about the occurrence of WRF in patients with AHF.
Aims
The Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) formula estimates glomerular filtration rate (GFR) better than the simplified Modification of Diet in Renal Disease (sMDRD) ...formula in numerous populations. It has not previously been validated in heart failure patients.
Methods and results
The GFR was measured in 120 patients with chronic systolic heart failure (CHF) using 125Iiothalamate clearance (GFRIOTH) and estimated using the sMDRD and CKD‐EPI equations. Accuracy, bias, and prognostic performance were compared. Cockcroft–Gault, CKD‐EPI serum cystatin C, and CKD‐EPI creatinine–serum cystatin C equations were compared in secondary analyses. Mean age was 59 ± 12 years, 80% were male. Mean LVEF was 29 ± 10%. Mean GFRIOTH was 74 ± 27 mL/min/1.73 m2, and mean estimated GFR was 66 ± 23 mL/min/1.73 m2 (CKD‐EPI) and 63 ± 21 mL/min/1.73m2 (sMDRD). CKD‐EPI showed less bias than sMDRD (–8 ± 15 vs. –11 ± 16 mL/min/1.73 m2, P < 0.001). Both equations underestimate at higher and overestimate at lower GFRIOTH. Eleven patients (9%) were accurately reclassified into lower CKD classes with CKD‐EPI. Cockcroft–Gault showed lower bias (–3 ± 16 mL/min/1.73 m2) but worse precision and accuracy. Cystatin C‐based estimation showed the lowest bias (–3 ± 14 mL/min/1.73 m2) and the best precision and accuracy. Prognostic value did not differ between all GFR estimates
Conclusion
The CKD‐EPI equation more accurately estimates measured GFR than the sMDRD equation in CHF patients, with less bias and greater accuracy and precision. The prognostic power of all GFR assessments was equivalent. Based on better performance and equal risk prediction, we believe the CKI‐EPI equation should be the preferred creatinine‐based GFR estimation method in heart failure patients, particularly those with preserved or moderately impaired renal function.
Aims
Our aim was to identify circulating microRNAs (miRNAs) associated with acute heart failure (AHF).
Methods and results
Plasma miRNA profiling included 137 patients with AHF from 3 different ...cohorts, 20 with chronic heart failure (CHF), 8 with acute exacerbation of COPD, and 41 healthy controls. Levels of circulating miRNAs were measured using quantitative reverse transcription–polymerase chain reaction (qRT–PCR). Plasma levels of miRNAs in patients with AHF were decreased compared with CHF patients or healthy subjects, whereas no significant changes were observed between acute COPD patients and controls. Fifteen miRNAs found in the discovery phase to differ most significantly between healthy controls and patients with AHF were further investigated in an extended cohort of 100 AHF patients at admission and a separate cohort of 18 AHF patients at different time points. Out of these 15 miRNAs, 12 could be confirmed in an additional AHF validation cohort and 7 passed the Bonferroni correction threshold (miR‐18a‐5p, miR‐26b‐5p, miR‐27a‐3p, miR‐30e‐5p, miR‐106a‐5p, miR‐199a‐3p, and miR‐652‐3p, all P < 0.00005). A further drop in miRNA levels within 48 h after AHF admission was associated with an increased risk of 180‐day mortality in a subset of the identified miRNAs.
Conclusions
Declining levels of circulating miRNAs were associated with increasing acuity of heart failure. Early in‐hospital decreasing miRNA levels were predictive for mortality in a subset of miRNAs in patients with AHF. The discovered miRNA panel may serve as a launch‐pad for molecular pathway studies to identify new pharmacological targets and miRNA‐based therapies.
Aim
The clinical value of single biomarkers at single time‐points to predict outcomes in patients with acute heart failure (AHF) is limited. We performed a multimarker, multi‐time‐point analysis of ...biomarkers for the prediction of post‐discharge clinical outcomes in high‐risk AHF patients.
Methods and results
A set of 48 circulating biomarkers were measured in the PROTECT trial which enrolled 2033 patients with AHF. Associations between baseline levels of biomarkers and outcomes (30‐day all‐cause mortality, 30‐day death or rehospitalization for renal/cardiovascular causes and 180‐day all‐cause mortality) were evaluated. Prognostic accuracies of baseline, days 2 or 3, 7, and 14 biomarker measurements were estimated and compared utilizing a time‐dependent area under the curve (AUC) analysis. Forty‐four biomarkers were significantly associated with outcomes, but 42 had limited prognostic value (C‐index < 0.70). However, multimarker models combining best‐performing biomarkers from different clusters had a much stronger prognostic value. Combining blood urea nitrogen (BUN), chloride, interleukin (IL)‐6, cTnI, sST‐2 and VEGFR‐1 into a clinical model yielded a 11% increase in C‐index to 0.84 and 0.78 for 30‐day and 180‐day all‐cause mortality, respectively, and cNRI of 0.86 95% CI 0.55–1.11 and 0.76 95% CI 0.57–0.87. Prognostic gain was modest for the 30‐day death/rehospitalization for cardiovascular or renal causes endpoint. Comparative time‐dependent AUC analysis indicated that late measurements provided superior accuracy for the prediction of all‐cause mortality over 180 days, with few exceptions including BUN and galectin‐3. However, the predictive value of most biomarkers showed a diminishing pattern over time irrespective of moment of measurement.
Conclusions
Multimarker models significantly improve risk prediction. Subsequent measurements, beyond admission, are needed for majority of biomarkers to maximize prognostic value over time, particularly in the long term.
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