In hospital mortality and outcomes of patients with acute decompensated diastolic heart failure with and without amyloidosis

Calling for Targeted Trials in Cardiorenal Syndromes

Cardiorenal syndrome type I (CRS I) is defined as the development of acute kidney injury (AKI) following acute decompensated heart failure (ADHF). The clinical significance of endothelial markers in ADHF-associated AKI has yet to be clarified. This study therefore investigated the biological processes linking ADHF and AKI with the aim of determining whether the plasma markers of endothelial injury and activation are associated with AKI in patients with ADHF. The study prospectively recruited 125 consecutive patients admitted to a coronary critical unit due to ADHF. Patients with and without AKI were compared in terms of soluble thrombomodulin (sTM), angiopoietin (Ang)-1 and −2 plasma levels as well as baseline characteristics. Among the study population, 14 (11.2%) patients developed CRS within 7 days after admission. The hemoglobin levels (median [IQR]11.3[10.8–12.6] vs. 13.5 [12.2–15.0] g/dL, p = 0.003) and baseline eGFR (66.5[35.7–87.9] vs. 78.5 [64.9–107.5] mL/minute/1.73m2, p = 0.044) of patients with CRS were lower than those of patients without CRS. Patients with CRS also presented elevated plasma levels of BNP (1317.5 [222.6–3375.5] vs. 258.2 [63.2–925.8] pg/mL, p = 0.008), Ang-2 (3993.0 [1561.3–15722.7] vs. 1805.9 [1196.9–3302.3] pg/mL, p = 0.006), and sTM (6665.7 [4707.1–11947.3] vs. 4132.2 [3338.0–5531.8] ng/mL, p < 0.001), compared to patients without CRS. Multivariate logistic regression analysis based on forward stepwise method identified that log sTM was the only independent risk factor for AKI (OR, 13.83; 3.02–63.28, p = 0.001). Furthermore, higher sTM levels were associated with AKI in patients with ADHF. These findings suggest a novel approach to dealing with kidney injury in the context of ADHF, involving the use of baseline biomarker profiles to identify individuals at risk of developing AKI. KEY MESSAGES The clinical significance of endothelial markers in acute decompensated heart failure (ADHF)-associated acute kidney injury (AKI) has not previously been clarified. This study revealed that markers of endothelial injury (i.e. plasma soluble thrombomodulin (sTM) levels) were higher in ADHF patients with AKI than in those without AKI. Multivariate analysis identified sTM level > cutoff value of 4,855.2 pg/mL as an independent factor associated with the development of AKI. sTM could potentially be used as a biomarker to predict the development of AKI in patients with heart failure. These findings suggest a novel approach to dealing with kidney injury in the context of ADHF, involving the use of baseline biomarker profiles to identify individuals at risk of developing AKI.

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.&amp;lt;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.&amp;lt;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.&amp;lt;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.&amp;lt;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

Cardiorenal Syndrome in Critical Care: The Acute Cardiorenal and Renocardiac Syndromes

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

eart failure with preserved ejection fraction (HFpEF) has been previously defined by various criteria, 1 with a common theme being the presence of preserved left ventricular ejection fraction. Defining a heart disease on the basis of a normal cardiac finding should beg the question: What is distinctly abnormal about the heart in HFpEF? Answering this question may aid in overcoming a track record of limited success to date with pharmacological approaches to HFpEF.

Background and Aims Impaired renal function is a common finding in patients with cardiac diseases and confers an adverse prognosis in this population. To evaluate the incidence, phenotypes and prognostic value of cardiorenal interrelations in patients with acute decompensated heart failure (ADHF) and non-ST-elevation acute coronary syndrome (NSTE-ACS). Method we examined 278 patients with ADHF (85.3% had anamnesis of symptomatic HF with frequent hospitalizations, 20.1% had ejection fraction &amp;lt;35%) and 288 with NSTE-ACS (64.9% developed myocardial infarction (MI)). In ADHF group in comparison with NSTE-ACS the patients were younger (69.7±10.2 vs 72±12.1 years, p&amp;lt;0.01), there were more males (55.4 vs 36.5%, p&amp;lt;0.001), smokers and alcohol abusers (47.8 and 30.6% vs 8 and 5.6%, p&amp;lt;0.001). The comorbidities were more typical for ADHF group: atrial fibrillation 46 vs 24% (p&amp;lt;0.001), obesity 55.8 vs 30.9% (p&amp;lt;0.001), anemia 40.6 vs 25.3% (p&amp;lt;0.001), diabetes mellitus 33.1 vs 23.3% (p&amp;lt;0.01). Chronic kidney disease (CKD) and acute kidney injury (AKI) were diagnosed according to KDIGO 2012 Guidelines. AKI phenotypes were identified depending on time of development (community- or hospital-acquired), persistency (transient or persistent), history of CKD (AKI de novo or AKI on CKD). Results Incidence of CKD in patients with ADHF and NSTE-ACS was 45 and 46.5%, CKD was first diagnosed on admission in 57.6 and 64.2% of patients respectively. In 7.6% cases of ADHF and 14.2% of NSTE-ACS groups the duration of impaired kidney function was unknown. No associations of existing CKD and in-hospital mortality were detected. Incidence of AKI in ADHF and NSTE-ACS groups was 43.5 and 37.2%. The hospital-acquired AKI, AKI on CKD and persistent AKI were found in 52.9, 47.9 and 46.3% of ADHF patients, and in 57.9, 58.9 and 50.5% in NSTE-ACS group respectively. In-hospital mortality was higher in patients with AKI in ADHF and NSTE-ACS groups (12.4 vs 5%, p&amp;lt;0.01 and 17.8 vs 3.3%, p&amp;lt;0.001). Mortality in patients with ADHF and hospital-acquired persistent AKI de novo and community-acquired persistent AKI on CKD was 41 and 29%, and in community-acquired transient AKI on CKD in the NSTE-ACS group – 29%. Conclusion Different cardiorenal interrelations were revealed in 75.2% of patients with ADHF and in 61.8% with NSTE-ACS. In patients with acute cardiac diseases high in-hospital mortality is tightly associated with phenotypes of hospital-acquired persistent AKI de novo and community-acquired persistent AKI on CKD in ADHF, and in community-acquired transient AKI on CKD in the NSTE-ACS.

ObjectiveThere are conflicting results among previous studies regarding the prognosis of heart failure with preserved ejection fraction (HFpEF) compared with heart failure with reduced ejection fraction (HFrEF). This study aimed...

Relation of Baseline Systolic Blood Pressure and Long-Term Outcomes in Ambulatory Patients With Chronic Mild to Moderate Heart Failure

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&lt;0.0001). In multivariable analysis in ADHF and CHF, log10NT-proBNP (HR=5.30, 95%CI 2.71–10.38, p&lt;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&lt;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).

Aim. To assess the risk factors and diagnostic significance of the N-terminal probrain natriuretic peptide (NT-proBNP) in patients with acute decompensated heart failure (ADHF) and diabetic kidney disease (DKD).Material and methods. A total of 125 patients with ADHF and type 2 diabetes (T2D) were examined. They were divided into 2 groups depending on the presence/ absence of chronic kidney disease (CKD). The first group consisted of 43 (34,4%) patients with DKD, the second — 82 (65,6%) without CKD. The inclusion criterion was the presence of ADHF and T2D. There were following exclusion criteria: cardiogenic shock, pulmonary edema, acute thromboembolic events, type 1 diabetes, prediabetes, acute coronary syndrome, stroke, prior transient ischemic attack (&lt;1 month old), dissecting aneurysm or aortic dissection, acute valvular disorders, major surgery (&lt;1 month old), cardiac trauma, infective endocarditis, acute hepatitis and cirrhosis, terminal CKD, alcohol abuse, non-cardiac edema, cancer, dementia and mental disorders.Results. With the development of a hypertensive crisis and an increase in diastolic blood pressure &gt;100 mm Hg, the odds ratio (OR) and the relative risk (RR) of ADHF in patients with DKD increases by 5,1 and 4,5 times, 2,5 and 1,8 times, respectively. In the presence of grade III-V premature ventricular contractions, OR and RR of ADHF in patients with DKD were 2,6 and 1,9, respectively. OR and RR of ADHD in patients with DKD and prior stroke or transient ischemic attack were 3,8 and 3,2, respectively. Verification of anemia at a hemoglobin level of 5 mmol/l, the OR of ADHF in patients with DKD increases by 3,7 times, the OR — by 2,3 times. The NT-proBNP &gt;1289 pg/ml is diagnostic for verifying ADHF in DKD patients with the sensitivity of 64,3% and specificity of 93,3%.Conclusion. Every third patient with ADHF and T2D is diagnosed with DKD. A certain range of risk factors for the development of ADHF in patients with DKD has been identified. As the glomerular filtration rate (GFR) decreases, the NT-proBNP level increases. With a decrease in GFR of 60 ml/min/1,73 m2 in patients with T2D, the diagnostic value of NT-proBNP &gt;1289 pg/ml should be considered to verify ADF.

To evaluate the prevalence, predictors, prognostic value of cardiorenal interrelations in patients with acute cardiovascular disease (CVD), and to develop an algorithm for stratification these patients at risk of acute kidney injury (AKI). 566 patients (pts) were examined: 278 with acute decompensated heart failure (ADHF) and 288 with non-ST-elevation acute coronary syndrome (NSTE-ACS). The levels of electrolytes, glucose, urea, creatinine were evaluated, glomerular filtration rate (GFR) was determined according to the formula CKD-EPI. Chest x-ray, electrocardiography at admission and in dynamics, echocardiography at admission with assessment of systolic and diastolic myocardial functions were performed. Chronic kidney disease (CKD), AKI, ADHF, NSTE-ACS were diagnosed according to Russian and international Guidelines. Mann-Whitney test and multivariate logistic regression analysis were considered significant if p&lt;0.05. Different variants of cardiorenal interrelations were revealed in 366 (64.7%) pts. CKD was diagnosed in 259 (45.8%), with more than half of the cases (61%) diagnosed for the first time at this hospitalization, 62 (11%) pts had signs of kidney damage of unknown duration (which did not allow to diagnose CKD). AKI occurred in 228 (40,3%) pts, more frequently in patients with ADHF vs with NSTE-ACS (43.5 and 37.2%). In all groups stage 1 of AKI was prevalent. In-hospital mortality was significantly higher in pts with AKI vs without AKI (14.9 vs 3.6%, p&lt;0.001). The risk of AKI was determined by kidney function and blood pressure levels at admission, and comorbidities. Prevalence of cardiorenal interactions in patients with acute CVD (ADHF and NSTE-ACS) was 64.7%. Development of AKI was associated with poor prognosis in both groups. Renal function and blood pressure levels on admission are the main predictors of AKI.

To the Editor, I am writing to express my appreciation for the recent publication by Umit Yuksek, "Red Cell Distribution Width Is an Independent Predictor of 1-Year Mortality in a Turkish Patient Population with Acute Decompensated Heart Failure" [1]. This study contributes significantly to our understanding of prognostic factors in acute heart failure, highlighting the importance of red cell distribution width (RDW) as an independent predictor of 1-year mortality in patients with acute decompensated heart failure. The methodology used in the study, which involved a cohort of 101 patients, provides an analysis of the predictive value of RDW as well as traditional clinical predictors. The finding that a 1% increase in RDW is associated with a 44% increase in 1-year mortality is particularly striking and emerging as a simple but powerful prognostic marker in clinical practice. In addition to the limitations mentioned by the author, there are a few other factors that could potentially impact the results. First, studies on the effect of demographic characteristics on the value of RDW show that RDW is associated with various clinical conditions and demographic factors [2]. It has been reported that RDW can be affected by a number of factors, such as age, gender, inflammation, coronary artery disease, heart failure, hyperlipidemia, diabetes mellitus, pneumonia, and chronic obstructive pulmonary disease. Patients with acute decompensated heart failure may also be frequently intertwined with these diseases during their initial admission. The fact that some of these important demographic characteristics were not clearly explained in the patient population of the study may be important in terms of influencing the results of the study. The criteria for inclusion or exclusion in the study are also not comprehensive and clear. We think that these should be specified in more detail. In addition, the non-invasive diagnosis of heart failure with preserved ejection fraction (HFpEF) is difficult and controversial. For this reason, it is recommended to use scoring systems like H2FPEF and HFA-PEFF for the diagnosis of HFpEF [3,4]. We believe that if any echocardiography or laboratory parameters other than the EF were evaluated while considering this patient group, it would be good to mention the methodology section. However, mentioning this issue in the limitations section may be useful if it is not mentioned. Second, when we look at the comparison of the clinical and laboratory characteristics of the subgroups with normal, high, and very high RDW values, it is noteworthy that factors such as Killip classification, mitral insufficiency, atrial fibrillation, cardiogenic shock, inotropic drug requirement, which may have significant effects on mortality in acute HEART FAILURE, do not have a significant relationship with high RDW. It also appears that even if it is not statistically significant, the EF value is positively correlated with RDW. As a result, despite this important success of RDW in showing a 1-year mortality estimate, it also has a weak relationship with many other mortality predictor parameters in acute heart failure, suggesting that unforeseen clinical conditions or parameters may potentially affect RDW in this study group. Statistically significant findings may not always be clinically or biologically significant. RDW may indicate that it is a clinically important variable, but this effect may be small and not make a significant difference in practice. The reason for coming to this conclusion is that the important limitations mentioned above may affect the study results. In conclusion, we believe that further research is necessary to investigate the mechanisms underlying the association between RDW and mortality in acute heart failure patients and to examine the potential of RDW to guide therapeutic interventions. We commend the author of this study, which not only enriches our understanding but also opens avenues for future research in acute heart failure management, and we thank the journal for publishing it. Yours sincerely

Background Cannabis is the most popular recreational drug in the United States but knowledge about its health implications remain limited. Cannabis use has been linked to acute myocardial infarction and congestive heart failure. The effect of cannabis use in acute decompensated heart failure in patients with Implantable Cardiac Defibrillators (ICDs) is not known. Objective In this study, we sought to explore the impact of cannabis use in patients with Implantable Cardiac Defibrillators (ICDs) admitted with acute decompensated heart failure. Methods We queried the 2019 National Inpatient Sample (NIS) database for all patients aged ≥18 with ICD devices admitted with acute heart failure. Patients were stratified into two groups based on Cannabis use. We excluded patients with opioid, amphetamine, psychostimulants, cocaine, sedative, and hallucinogen abuse disorders to eliminate the effect of polysubstance use. Results Of the 174,295 hospitalization events for acute decompensated heart failure with ICDs, 1824 were noted to have diagnosis of cannabis use (CU). Patients with CU were younger (mean age 52.4y vs 68.5y) and mostly male (81.1% vs 18.9%). CU group had lower prevalence rates for anemia, atrial fibrillation, coronary artery disease, diabetes, cirrhosis, chronic kidney disease and hypothyroidism. They had higher rates of alcoholism, tobacco use and depression. The primary outcome studied was inpatient mortality. Secondary outcomes include cardiac arrest, myocardial infarction, cardiogenic shock, ventricular tachycardia, ventricular fibrillation, stroke, respiratory failure, pleural effusion, acute kidney injury, length of stay (LoS) and hospital charges. Patients in CU group were noted to have decreased length of stay (reduction in adjusted mean LoS: 2.14 days, P=0.000), mortality (adjusted OR: 0.14, P=0.006) and respiratory failure (adjusted OR: 0.53, P=0.009). Conclusion Among patients with implantable cardiac defibrillator admitted for acute decompensated heart failure, cannabis users were younger and mostly male. These patients were noted to have decreased length of stay, inpatient mortality, and respiratory failure. Funding Acknowledgement Type of funding sources: None.

A Simple Pediatric Heart Failure Symptom Score for Children Hospitalized with Acute Decompensated Heart Failure