Acute Decompensated Heart Failure

Recent Trends in the Incidence, Treatment, and Prognosis of Patients With Heart Failure and Atrial Fibrillation (the Worcester Heart Failure Study)

Background: Myocardial injury (INJ) expressed by elevated high-sensitivity troponin (hs-Tn) is common in heart failure (HF), due to cardiovascular and non-cardiac conditions. The mechanisms of INJ in acute decompensated HF (ADHF) versus chronic HF (CHF) are still debated. This study’s purpose was to evaluate the determinants of elevated hs-TnT in ADHF and CHF. Methods: We retrospectively analyzed consecutive HF patients with hs-TnT measured on admission, hospitalized in a tertiary-care hospital. Rehospitalizations, acute coronary syndromes, embolisms, infections, autoimmunity and malignancy were excluded. Cut-off point for hs-TnT was 14 ng/L. Results: Our study included 488 HF patients, 56.55% with ADHF. Mean age was 72.52±10.09 years. 53.89% were females. 67.75% ADHF and 45.75% CHF patients had elevated hs-TnT. Median hs-TnT was higher in ADHF versus CHF (21.05[IQR 12.74-33.81] vs 13.20[IQR 7.93-23.25], p<0.0001). In multivariable analysis in ADHF and CHF, log10NT-proBNP (HR=5.30, 95%CI 2.71–10.38, p<0.001, respectively HR=5.49, 95%CI 1.71–17.57, p=0.004) and eGFR (HR=0.72, 95%CI 0.62–0.85, p<0.001, respectively HR=0.71, 95%CI 0.55–0.93, p=0.014) were independent predictors for increased hs-TnT. Independent factors associated with elevated hs-TnT in ADHF were male sex (HR=2.52, 95%CI 1.31-4.87, p=0.006) and chronic pulmonary obstructive disease (COPD) (HR=10.57, 95%CI 1.26-88.40, p=0.029), while in CHF were age (HR=2.68, 95%CI 1.42-5.07, p=0.002) and previous stroke (HR=5.35, 95%CI 0.98-29.20, p=0.053). Conclusion: HF severity, expressed by NT-proBNP levels, and kidney disease progression, expressed by eGFR, were independent predictors associated with increased hs-TnT in both ADHF and CHF. Specific independent predictors were also indentified in ADHF (male sex, COPD) and CHF (age, history of stroke).

Rafael Correo, de izquierdas, y Alvaro Noboa, magnate conservador, vencieron con un discurso clientelista en el pais mas inestable de America Latina.

Background The discovery of new markers for acute kidney injury (AKI) in acute decompensated heart failure (ADHF) has been hampered by an incomplete understanding of the pathological processes underlying AKI in ADHF. Purpose In a sheep model of ADHF, we investigated changes in kidney gene expression in response to the development of, and recovery from, ADHF. Methods We collected serial kidney biopsies from 6 sheep prior to rapid cardiac pacing (day 0), after development of ADHF (pacing @220bpm for 14 days), and at the end of a 25-day (non-pacing) recovery period. Serial biopsies were supplemented with kidney samples collected post-mortem from animals undergoing a similar pacing/recovery protocol, giving a total of 11 “baseline” (B), 13 “heart failure” (HF) and 8 “recovery” (R) samples. We prepared RNA-Sequencing libraries using total RNA and Illumina TruSeq stranded mRNA library kits. Hormonal, haemodynamic, biochemical and urine measurements were also performed in all sheep before, during, and after development of ADHF. The study followed the principles of laboratory animal care and was approved by our institution's Animal Ethics Committee. Results We observed profound changes in hormonal, haemodynamic, biochemical and urine measures of cardio-renal injury in all sheep, confirming simulation of the peripheral consequences of ADHF, including clinically-relevant kidney dysfunction. This occurred in conjunction with altered kidney expression of 982 genes during ADHF development and 1,807 genes during ADHF recovery (p adj.<0.05, Fig 1). During ADHF development, changes in kidney gene expression were associated with activation of the pro-inflammatory p38 MAPK pathway and repression of several anti-inflammatory and reno-protective pathways, including eNOS signalling (all p adj.<0.001). In contrast, during ADHF recovery, changes in kidney gene expression were associated with reactivation of reno-protective pathways repressed during ADHF development, activation of anti-fibrotic pathways (including PTEN signalling) and repression of pathways that mediate inflammation and renal injury (including NF-kB signalling, all p adj.<0.001). Among 431 ADHF “responsive” genes (i.e. those that increased during ADHF development and decreased during ADHF recovery, or vice versa, Fig. 1), 37 genes encoded proteins detectable in plasma or urine and may represent markers of kidney repair in ADHF. Although most gene expression changes were transient, 192 genes remained altered after 4-weeks recovery (p adj.<0.05, Fig 1). Of these, 13 genes were predicted to encode proteins detectable in plasma or urine and may represent persistent markers of kidney injury in ADHF. Conclusion Our data provide the first insight into the gene pathways associated with kidney injury and repair in ADHF, in an established ovine model. Understanding the pathological processes underlying AKI in ADHF may enable discovery of novel markers for monitoring kidney injury and repair in ADHF. Figure 1. Genes altered in the kidney in ADHF Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Health Research Council of New Zealand, Heart Foundation of New Zealand

Introduction: There has been little focus on hospitalized acute decompensated heart failure (ADHF) that develops after admission, which may occur because of comorbid conditions, over-administration of fluid or post-surgical complications. Aims: To compare patient characteristics, case fatality, and hospital length of stay (LOS) associated with ADHF that develops after hospital admission as compared to those with ADHF at admission. Methods: Hospitalizations with possible ADHF were sampled, based on HF ICD codes, among those aged > 55 years from the four communities of the Atherosclerosis Risk in Communities Study (2005-2010). Medical records were abstracted with events classified by physician panel or computer classified. Case fatality was obtained through the National Death Index. We identified 4,503 (unweighted) events with definite/probable ADHF, after excluding those with unknown time of decompensation (n=81), hospital transfers (n=102), and race other than black or white (n=118). Demographic and clinical characteristics were compared by ADHF onset (at/after admission). Logistic regression was used to evaluate the association of ADHF onset with in-hospital mortality, and 28-days and one-year mortality, adjusted for demographics and comorbidity. Linear regression was used to evaluate the association of ADHF onset with log-transformed hospital LOS, adjusted for demographics. All analyses were weighted to account for the stratified sampling design. Results: Of 21,052 (weighted) ADHF events, 7.4% (n=1561) developed ADHF after admission. Patients with ADHF occurring after admission were older (mean: 79 vs. 75 years), and more likely white and female. Those with ADHF at admission were more likely to have a positive smoking history, COPD, and to be on dialysis. Presence of diabetes, hypertension and coronary artery disease were not significantly different between groups. In hospital mortality (16.5% vs. 6.3%; OR= 2.7, 95% CI=1.9-3.8) and 28-day mortality (23.9% vs. 10.1%; OR= 2.4, 95% CI=1.7-3.4) was higher among those who developed ADHF after admission. One-year case fatality was similar (39.4% vs. 33.6%; OR= 1.2, 95% CI=0.9-1.6). Unadjusted mean LOS was longer for those with ADHF occurring after admission (12.8 days, 95% CI=11.8-13.8) than those with ADHF at admission (7.2 days, 95% CI=6.8-7.6). The adjusted and geometric mean LOS was 1.3 days (95% CI=1.2-1.4) longer for those who developed ADHF after admission. Conclusion: Although patients with ADHF onset after admission were slightly older, differences in comorbidity do not indicate an easily identifiable subgroup for closer in-hospital monitoring. Development of ADHF after admission was associated with an alarmingly high early case fatality and longer hospital LOS compared to those with ADHF at hospital admission.

Can saline repletion be the true TARGET for achieving fluid balance in acute heart failure?

Calling for Targeted Trials in Cardiorenal Syndromes

Introduction The incidence of heart failure has exponentially increased over the last few decades and acute decompensated diastolic heart failure is one of the leading causes of hospitalization and readmission. Cardiac amyloidosis is one of the rapidly progressing heart conditions. It occurs due to amorphous proteinaceous material called amyloid into the extracellular space of the heart. The infiltration of the heart from amyloid protein has a broad spectrum of presentation, including diastolic heart failure. Purpose Heart failure due to amyloidosis is characterized by diastolic dysfunction resulting from restrictive cardiomyopathy. The outcomes of hospitalized patient with acute decompensated diastolic heart failure in amyloidosis patients compared to those without amyloidosis is not well defined. Methods We conducted a retrospective cohort study by utilizing the National Inpatient sample database from 2017. Using International Classification of disease (ICD)-10 codes, patients with the diagnosis of acute and acute on chronic diastolic heart failure were enrolled in the study. They were further stratified based on the presence of amyloidosis. The primary outcome was to measure in-hospital mortality, while secondary outcomes included development of acute kidney injury (AKI), Acute respiratory failure (ARF), shock and arrhythmias. Results Out of the 915,694 patients with Acute Decompensated diastolic heart failure, about 2270 had amyloidosis as secondary diagnosis. 6.1% of ADHF and amyloidosis died in hospital, compared to 4.2% in those without amyloidosis (aOR=1.35 CI=0.89–2.05, p=0.197). On multivariate analysis, patients with Amyloidosis had increased odds of developing AKI (aOR=1.40 CI 1.13–1.72, p=0.001), Cardiogenic shock (aOR=2.67 CI 1.56–4.55, p<0.001) and arrhythmias (aOR=1.34, CI 1.10–1.64, p=0.004). The incidence of ARF was however lower in patients without amyloidosis compared to those with it (aOR=0.60, CI 0.47–0.75, p<0.001). Conclusion Amyloidosis is one of the underappreciated and underdiagnosed causes of heart failure. Our study shows an increased risk of complications in acute decompensated heart failure with the presence of amyloidosis. Thus, physicians must be aware of this clinical entity for early diagnosis as patients with advanced disease are likely to have poor prognoses. Funding Acknowledgement Type of funding sources: None.

Background. Medico-statistical portrait of patient are a fairly new concept. Materials and methods. 71 patients with intermediate ejection fraction of left ventricle (ILVEF) under acute decompensation of chronic heart failure were examined, 51 of them were male (71.8%) and 20 female (28.2%). Main cause of cronic heart failure was ischemic heart disease and arterial hypertension. The Charlson comorbidity index and Stevenson’s hemodynamic profile of patients. The average age of the individuals is 65.6 ± 12.1 years. Statistical processing of the data was carried out using the method of multifactor analysis using SPSS 23 and the Microsoft Office Excel 10.0 package. Results. Main features of portrait of a patient with ILVEF with acute decompensation of heart failure, which has an high risk of death, is a male aged 64 to 71 years, with a Charlson’s comorbidity index equal to 5 points and higher, as well as a hemodynamic profile of B or C. Portrait of a patient with ILVEF who has a low risk of death - a male / female aged 55 to 64 with a Charlson’s index from 1 to 4 points, as well as hemodynamic profile A and L. The conclusion. This article describes a creation of mathematical model for patients with ILVEF and acute decompensation of chronic heart failure under background of comorbidity and hemodynamics with a check of the obtained models using ROC-analysis. (For citation: Skorodumova EG, Kostenko VA, Skorodumova EA, et al. Portrait of the patient with intermediate ejection fraction of the left ventricle on the background of acute decompencation of heart failure. Herald of North-Western State Medical University named after I.I. Mechnikov. 2018;10(2):87-91. doi: 10.17816/mechnikov201810287-91).

IN THIS ISSUE OF JAMA, 2 ARTICLES REPORT FINDINGS FROM the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) clinical trials program. Konstam et al report the overall longterm effects of tolvaptan in terms of safety and clinical outcomes for patients with worsening heart failure (HF) requiring hospitalization. Gheorghiade et al report shortterm effects of tolvaptan for acute symptom relief in these same patients, but presented as 2 trials that were based on study center assignment following completion of patient enrollment and randomization in the long-term trial. The aggregate findings demonstrate that tolvaptan relieves some symptoms associated with acute decompensated heart failure (ADHF) and has no demonstrable evidence of harm such as worsening of renal failure, but importantly, does not reduce mortality or HF-related morbidity at 1 year. In the context of ADHF, these are noteworthy findings. To date, no other therapeutic intervention has been demonstrated in large-scale randomized, placebo-controlled studies to positively influence symptoms in ADHF without generating a question of harm. Inotropes have been associated with increased mortality risk, and calcium sensitizers have been associated with increased cardiovascular mortality. Nesiritide was shown to relieve dyspnea and to reduce pulmonary congestion over the short term, but also was associated with increased intermediate-term mortality risks. Traditional vasodilator therapy relieves HF symptoms, but neither nitroglycerin nor nitroprusside has been subjected to prospective randomized controlled study, and effects on mortality are unknown. Even diuretics, which clearly relieve congestion, have uncertain effects on outcomes. Addressing the challenge of ADHF has been daunting. Acute decompensated HF accounts for more than 1 million acute hospitalizations per year in the United States at an annual cost of more than $30 billion and is associated with significant mortality. The risk of inpatient death is approximately 4% (but ranges from 2%-22%), and the risk of death/rehospitalization at 60 to 90 days after an episode of ADHF is 36%. At the core of this challenge, however, is the limited understanding of the pathophysiology of ADHF. While hemodynamic disturbances are clearly responsible for the observed signs and symptoms, plausible causative mechanisms that trigger acute decompensation, eg, ventricular injury and augmented neurohormonal activation, remain uncertain. Thus, therapy for ADHF is relegated to correcting perturbed hemodynamics. Comparison is made with the evolution of therapy for chronic HF—targeting hemodynamic abnormalities did not yield meaningful clinical benefits, but elucidation of relevant pathophysiological mechanisms followed by appropriately focused interventions in largescale trials resulted in salutary improvements. A similar approach is needed for ADHF. Another challenge of ADHF involves clinical trial design and construct. The studies to date have been small to moderate short-term hemodynamic or symptom-focused designs, constructed primarily to meet regulatory requirements. Important questions, including mechanistic hypotheses and the effect of interventions on rehospitalizations/mortality, have been inadequately studied. Trials in ADHF have also been confounded by considerable heterogeneity of the patient phenotype. Patients with ADHF are older, represent a mix of new-onset HF and decompensated chronic HF, have both reduced and preserved ejection fraction HF, have equal gender representation, and frequently have a number of important comorbidities, especially renal insufficiency. Moreover, “standard therapy” does not truly exist, as there are no evidence-based interventions proven to reduce morbidity and mortality associated with ADHF. Guidelines for ADHF have recently been put forward, but the treatment algorithms are sparse and focus on hemodynamic targets. The strategy is to relieve symptoms preferentially with diuretic use, including high-dose loop diuretics and continuous diuretic infusions (the safety of which is not known in HF), and to add vasodilator therapy (nitroglycerin or nitroprusside) if adjunctive approaches are needed. Inotropes are reserved for impending or frank shock but are otherwise dissuaded. Ultrafiltration represents at best an emerging technology with intriguing preliminary data but limited applications.

Background: Recent study demonstrated paradoxical relationship between body mass Index (BMI) and all cause mortality in patients with acute decompensated heart Failure (ADHF), where higher BMI was associated with decreased mortality. We sought to test whether this relationship exists between BMI and ADHF readmissions Methods: Consecutive patients presented to the emergency department from March 2014 to July 2015 with the diagnosis of ADHF were analyzed in a retrospective cohort study. Cohort was grouped in to prespecified BMI categories; normal weight (BMI <26 Kg/m2 ), Over weight (BMI 25-30 Kg/m2 ) and Obese (BMI >30 Kg/m2 and above). Primary endpoints were incidence of 30 day ADHF readmission and time to first ADHF readmission from the index hospitalization. Patients with end stage COPD on home O2, cirrhosis and end stage renal failure on dialysis were excluded. Unplanned hospitalizations due to other cause than ADHF were excluded. ADHF hospitalizations were adjudicated by an independent blinded clinician Results: Cohort (N=188) consisted 51(27.1%) normal weight, 61 (32.4%) over weight and 76 (40.4%) obese patients. Females were 63% (N=119), patients with heart failure with preserved ejection fraction were 47% (N=90), Obese [BMI 31(28-38) Kg/m2; Median (IQR)] patients were younger (median age; 77 years vs 83 years; P=0.002), whereas other covariates were similar between groups. In median follow up of 1.2 years, total 30 day ADHF readmissions were 32 and total ADHF admissions were 214. Incidence of both 30 day and total ADHF readmissions were similar in all 3 BMI categories; ANOVA P=0.18 (30 day ADHF readmissions) and P= 0.62 (total ADHF readmissions). Obesity was neither associated with risk for 30 day readmission; OR=0.64 (CI: 0.20 - 2.0; P= 0.45) nor with the time to first ADHF readmission from the index hospitalization; log rank P=0.5 (Figure 1) Conclusions: Higher BMI is not protective against ADHF readmissions in patients with ADHF. Further studies are needed in larger data sets to validate our findings.

Cardiac Natriuretic Peptide And Cgmp Impairment In Human Decompensated Heart Failure: Employing A Novel Ex Vivo Natriuretic Peptide/GC-A/cGMP Potency Assay To Evaluate Natriuretic Peptide Therapeutic Capacity

Loop diuretics are the first-line treatment for volume overload in acute decompensation of congestive heart failure (AHF). Loop diuretic resistance is common due to pharmacologic tachyphylaxis. Therefore, thiazide and thiazide-like diuretics are often used as add-on therapy to combine two different pharmacologic mechanisms. This systemic review and meta-analysis aimed to synthesize the current evidence on the efficacy and safety of metolazone and other thiazide-like diuretics in AHF. PRISMA guidelines were followed in conducting this systematic review. PubMed, Scopus, PubMed Central, and Embase databases were searched using relevant keywords for studies published before 5 Jan 2022. Abstract and title screening was performed, followed by full-text screening using the Covidence software. Data were extracted, and analysis was done using Cochrane Review Manager (RevMan v5.1). The results were reported in odds ratio and mean difference with 95% confidence intervals. Out of 2999 studies identified by database search, eight studies met the inclusion criteria (2 RCTs and 6 cohort studies). Pooled analysis using a random-effects model showed no difference in mean difference among the metolazone group and control group for 24 hours total urine output (MD 69.32, 95% CI -638.29 to 776.94; n = 551; I2 = 84%), change in urine output in 24 hours (MD -284.09, 95% CI -583.99 to 15.81; n = 345; I2 = 0%), 48 hours total urine output (MD -465.62, 95% CI -1302.22 to 370.99; n = 242; I2 = 0%) and urine output at 72 hours (MD -13.24, 95% CI -90.88 to 64.40; n = 205; I2 = 0%). However, studies with furosemide only in the comparator arm, 24 hours of total urine outcome favored metolazone (MD 692.70, 95% CI 386.59 to 998.82; n = 334; I2 = 0%). There was no difference between the two groups in the rate of adverse events, loss of weight, mortality, or readmission rates. Metolazone therapy in diuretic resistant AHF may improves urine output and facilitates achieving a net negative balance. Thus, metolazone and thiazide-like diuretics can be used as add-on therapy in acute decompensation of heart failure, especially in diuretic resistance.

Increased left ventricular filling pressure is a hallmark of heart failure (HF) caused by left ventricular dysfunction (LVD). Within the closed hemodynamic system, increased LV filling pressure results in elevated pressures in the left atrium and pulmonary venous vasculature. When pulmonary hypertension (PH, defined by mean pulmonary artery pressure [mPAP] >25 mm Hg) is associated with an abnormally elevated pulmonary capillary wedge pressure (PCWP >15 mm Hg) or left ventricular end-diastolic pressure (LVEDP >18 mm Hg),1 it has been variably termed World Health Organization (WHO) Group 2 PH,1 pulmonary venous hypertension,2 “postcapillary PH,”3 or “passive PH.”4 Article see p 644 Patients with LVD also have a propensity to develop a precapillary pulmonary arterial contribution to PH, reflected by an increased transpulmonary gradient (TPG, defined as mPAP-PCWP that exceeds 12 to 15 mm Hg) or an elevated pulmonary vascular resistance (PVR, defined as TPG/cardiac output that exceeds 2.5 to 3 Wood units [WU]).5,6 This type of PH, which is “out of proportion” to underlying left-sided disease in the setting of normalized volume status, has been termed “mixed PH,” given both precapillary and postcapillary contributions to elevated PAP.7 PH in HF can be simplistically organized along 2 sequential dyads: (1) the presence or absence of a significant precapillary contribution to elevated PAP (ie, mixed PH as opposed to purely passive PH) and (2) if present, the relative fixed (ie, nonreversible with lowering left-sided filling pressures) or reactive (ie, reversible with reduction of left-sided filling pressures) character of the precapillary contribution to PH (Figure). Figure. Diagnostic framework for pulmonary hypertension in heart failure (HF). mPAP indicates mean pulmonary artery pressure; PCWP, pulmonary capillary wedge pressure; PVR, pulmonary vascular resistance; and PH, pulmonary hypertension. There are no widely established cut-points to define PVR and transpulmonary …

THE AIM: to evaluate the morphological picture and its relationship with markers of acute kidney injury and other prognostic parameters in patients with severe fatal acute decompensation of heart failure (ADHF).PATIENTS AND METHODS: material obtained from 62 patients 47–82 years old (mean age 72.8±2.1 years) with severe acute decompensation of chronic heart failure resulting in death. The red cell distribution width, erythrocyte sedimentation rate haemoglobin, creatinine, total bilirubin, C-reactive protein content in blood at admission and shortly before death were determined. Autopsy with subsequent detailed examination of renal tissue was performed in all cases.RESULTS: The average duration of hospitalization of deceased patients with ADHF was 6,9±1,1 days. The main cause of death in 25 patients (40,3%) was pulmonary oedema due to pulmonary embolism, or against the background of heart failure, its acute decompensation developed – 37 patients (59,7%). On autopsy acute tubular injury was found in 36 patients (58.1%), with its direct strong correlation with the red cell distribution width, creatinine level, C-reactive protein; medium strength correlation with erythrocytes, total bilirubin; weak strength correlation – with transaminases was revealed.CONCLUSION: In fatal ADHF, AKI occurred with high frequency and was characterized mainly by acute tubular epithelial injury of varying severity. Acute kidney injury in fatal ADHF was strongly associated with elevated levels of CRP, RDW, and creatinine, increased heart weight, and the presence of hydrothorax. There was a correlation of medium strength with decreased red blood cell count and increased total bilirubin levels, and a weak correlation with elevated transaminase concentrations. Acute kidney injury is one of the components of thanatogenesis associated with the combined effect of inflammatory factors.