Heart Failure and Pancreas Exocrine Insufficiency:Pathophysiological Mechanisms and Clinical Point of View

Heart failure is associated with decreased tissue perfusion and increased venous congestion that may result in organ dysfunction. This dysfunction has been investigated extensively for many organs, but data regarding pancreatic (exocrine) dysfunction are scarce. In the present review we will discuss the available data on the mechanisms of pancreatic damage, how heart failure can lead to exocrine dysfunction, and its clinical consequences. We will show that heart failure causes significant impairment of pancreatic exocrine function, particularly in the elderly, which may exacerbate the clinical syndrome of heart failure. In addition, pancreatic exocrine insufficiency may lead to further deterioration of cardiovascular disease and heart failure, thus constituting a true vicious circle. We aim to provide insight into the pathophysiological mechanisms that constitute this reciprocal relation. Finally, novel treatment options for pancreatic dysfunction in heart failure are discussed

Preoperative cardiac screening using NT-proBNP in obese patients 50 years and older undergoing bariatric surgery:a study of 310 consecutive patients

Background: Obesity is associated with cardiovascular (CV) risk factors and diseases. Because bariatric surgery is increasingly performed in relatively elderly patients, a risk for pre- and postoperative CV complications exists. Objectives: We aimed to assess the value of plasma N-terminal-probrain natriuretic peptide (NT-proBNP) as a CV screening tool. Setting: High-volume bariatric center. Methods: Between June 2019 and January 2020, all consecutive bariatric patients 50 years and older underwent preoperative NT-proBNP assessment in this cohort study to screen for CV disease. Patients with elevated NT-proBNP (≥125 pg/mL) were referred for further cardiac evaluation, including electrocardiography and echocardiography. Results: We included 310 consecutive patients (median age, 56 years; 79% female; body mass index = 43±6.5 kg/m2). A history of CV disease was present in 21% of patients, mainly atrial fibrillation (7%) and coronary artery disease (10%). A total of 72 patients (23%) had elevated NT-proBNP levels, and 67 of them underwent further cardiac workup. Of these 67 patients, electrocardiography (ECG) showed atrial fibrillation in 7 patients (10%). On echocardiography, 3 patients had left ventricular ejection fraction (LVEF) <40%, 9 patients had LVEF 40%–49%, and 13 patients had LVEF ≥50% with structural and/or functional remodeling. In 2 patients, elevated NT-proBNP prompted workup leading to a diagnosis of coronary artery disease and consequent percutaneous coronary intervention in 1 patient. Conclusions: Elevated NT-proBNP levels are present in 23% of patients 50 years and older undergoing bariatric surgery. In 37% of them, there was echocardiographic evidence for structural and/or functional remodeling. Further studies are needed to assess if these preliminary results warrant routine application of NT-proBNP to identify patients at risk for CV complications after bariatric surgery

Quality of Life and Depressive Symptoms in the Elderly:A Comparison Between Patients With Heart Failure and Age- and Gender-Matched Community Controls

Background: Comparisons of heart failure (FIF) patients with an unselected healthy sample in terms of quality of life (QoL) and depressive symptoms might prove misleading. We compared QoL, and depressive symptoms of a HF population with an age- and gender-matched sample of community dwelling elderly. Methods and Results: Data were collected from 781 HF patients (36% female., age 72 +/- 9; New York Heart Association II-IV) and 781 age- and gender-matched community-dwelling elderly. Participants Completed the Medical Outcome Study 36-item General Health Survey, the Cantril's Ladder of life, and the Center for Epidemiological Studies-Depression scale (CES-D). Analysis of variance techniques e with Welch F test and chi-square tests were used to describe differences in QoL and depressive symptoms between different groups. For both men and women with HF, QoL was reduced and depressive symptoms were elevated when compared with their elderly counterparts (CES-D >= 16: 39% vs. 21 %, P <.001). HF patients had more chronic conditions--specifically diabetes and asthma/chronic obstructive pulmonary disease. Impaired QoL and depressive symptoms were most prevalent among HF patients with comorbidities. Prevalence was also higher in HF patients in the absence of these conditions. Conclusions: HF has it large impact on QoL and depressive symptoms, especially in women with HF. Differences persist, even in the absence of common comorbidities. Results demonstrate the need for studies of representative HF patients with direct comparisons to age- and gender-matched controls. (J. Cardiac Fail 2009;15:17-23

Predictors of non-pharmacological intervention in patients with paroxysmal atrial fibrillation:Value of neuroticism

Background: Non-pharmacological intervention is gaining increasing popularity in the treatment of patients with paroxysmal atrial fibrillation. We sought to investigate which factors play a role in the choice for non-pharmacological intervention with a particular focus on neuroticism. Methods: The study group comprised 73 patients with paroxysmal atrial fibrillation (mean age 55 13 years, 50 males). On average, patients had a 3-year-history of one symptomatic paroxysm per week lasting 2 It. The degree of neuroticism was assessed using the short scale Eysenck Personality Questionnaire. Results: During a mean follow-up period of 7.0 +/- 0.6 years, 20 patients (27%) underwent a non-pharmacological intervention for atria] fibrillation including His bundle ablation (n=1), maze operation (n=4), DDDR-pacemaker (n=10), pulmonary vein ablation (n=5). Multivariate regression analysis showed that age <55 years (odds ratio 5.3, 95% CI 1.1-24.5), frequency of paroxysms of atrial fibrillation > 1 per week (odds ratio 5.9, 95% CI 1.2-28.5) and total number of anti-arrhythmic drugs (class I and III) used > 2 (odds ratio 3.4, 95% CI 1.6-6.9) were predictive of non-pharmacological intervention (all p <0.05). In contrast, the degree of neuroticism was similar in patients who underwent non-pharmacological intervention as opposed to patients who did not undergo non-pharmacological intervention (4.5 +/- 3.3 vs. 4.0 +/- 2.9, p = NS). Conclusions: On the basis of this small study, neuroticism would not appear to play an important role in the decision to perform a nonpharmacological intervention. Instead, the data indicate that younger patients with pharmacologically refractory atrial fibrillation more often undergo non-pharmacological intervention. (c) 2005 Elsevier Ireland Ltd. All rights reserved

Frequency of and Prognostic Significance of Cardiac Involvement at Presentation in Hereditary Transthyretin-Derived Amyloidosis and the Value of N-Terminal Pro-B-Type Natriuretic Peptide

The aim of this study is to assess the prevalence of cardiac involvement in hereditary transthyretin-derived (ATTRm) amyloidosis at the time of diagnosis and to determine the diagnostic and clinical value of N-terminal pro-B-type natriuretic peptide (NT-proBNP). The University Medical Center Groningen is the national center of expertise for amyloidosis. All consecutive patients between 1994 and 2016 with ATTRm amyloidosis were followed prospectively. Baseline was set at the time of the first positive biopsy. All patients underwent a standard cardiac and neurologic work-up. Cardiac involvement was defined by otherwise unexplained left and/or right ventricular wall hypertrophy on cardiac ultrasound and/or advanced conduction disturbances. Seventy-seven patients had ATTRm amyloidosis and were included in the study. The TTR V30M mutation was present in 30 patients (39%). In both the V30M and the non-V30M groups, the neurologic presentation dominated (77% vs 51%), whereas cardiac presentation was infrequent (7% vs 15%). Clinical work-up showed that cardiac involvement was present at baseline in 51% of all patients irrespective of genotype and was associated with increased overall mortality (hazard ratio 5.95, 95% confidence interval 2.12 to 16.7), independent from clinical confounders. At a cutoff level of 125 ng/L, NT-proBNP had a sensitivity of 92% for establishing cardiac involvement. In conclusion, irrespective of the frequent noncardiac presentation of ATTRm amyloidosis, cardiac involvement is already present at diagnosis in half of the patients and is associated with increased mortality. NT-proBNP is a useful marker to determine cardiac involvement in this disease

Elevated plasma galectin-3 is associated with near-term rehospitalization in heart failure:A pooled analysis of 3 clinical trials

BackgroundRehospitalization is a major cause for heart failure (HF)–related morbidity and is associated with considerable loss of quality of life and costs. The rate of unplanned rehospitalization in patients with HF is unacceptably high; current risk stratification to identify patients at risk for rehospitalization is inadequate. We evaluated whether measurement of galectin-3 would be helpful in identifying patients at such risk.MethodsWe analyzed pooled data from patients (n = 902) enrolled in 3 cohorts (COACH, n = 592; PRIDE, n = 181; and UMD H-23258, n = 129) originally admitted because of HF. Mean patient age was between 61.6 and 72.9 years across the cohorts, with a wide range of left ventricular ejection fraction. Galectin-3 levels were measured during index admission. We used fixed and random-effects models, as well as continuous and categorical reclassification statistics to assess the association of baseline galectin-3 levels with risk of postdischarge rehospitalization at different time points and the composite end point all-cause mortality and rehospitalization.ResultsCompared with patients with galectin-3 concentrations less than 17.8 ng/mL, those with results exceeding this value were significantly more likely to be rehospitalized for HF at 30, 60, 90, and 120 days after discharge, with odds ratios (ORs) of 2.80 (95% CI 1.41-5.57), 2.61 (95% CI 1.46-4.65), 3.01 (95% CI 1.79-5.05), and 2.79 (95% CI 1.75-4.45), respectively. After adjustment for age, gender, New York Heart Association class, renal function (estimated glomerular filtration rate), left ventricular ejection fraction, and B-type natriuretic peptide, galectin-3 remained an independent predictor of HF rehospitalization. The addition of galectin-3 to risk models significantly reclassified patient risk of postdischarge rehospitalization and fatal event at each time point (continuous net reclassification improvement at 30 days of +42.6% [95% CI +19.9%-65.4%], P < .001).ConclusionsAmong patients hospitalized for HF, plasma galectin-3 concentration is useful for the prediction of near-term rehospitalization

Biomarker profiles of acute heart failure patients with a mid-range ejection fraction

OBJECTIVES: In this study, the authors used biomarker profiles to characterize differences between patients with acute heart failure with a midrange ejection fraction (HFmrEF) and compare them with patients with a reduced (heart failure with a reduced ejection fraction [HFrEF]) and preserved (heart failure with a preserved ejection fraction [HFpEF]) ejection fraction. BACKGROUND: Limited data are available on biomarker profiles in acute HFmrEF. METHODS: A panel of 37 biomarkers from different pathophysiological domains (e.g., myocardial stretch, inflammation, angiogenesis, oxidative stress, hematopoiesis) were measured at admission and after 24 h in 843 acute heart failure patients from the PROTECT trial. HFpEF was defined as left ventricular ejection fraction (LVEF) of ≥50% (n = 108), HFrEF as LVEF of &lt;40% (n = 607), and HFmrEF as LVEF of 40% to 49% (n = 128). RESULTS: Hemoglobin and brain natriuretic peptide levels (300 pg/ml [HFpEF]; 397 pg/ml [HFmrEF]; 521 pg/ml [HFrEF]; ptrend &lt;0.001) showed an upward trend with decreasing LVEF. Network analysis showed that in HFrEF interactions between biomarkers were mostly related to cardiac stretch, whereas in HFpEF, biomarker interactions were mostly related to inflammation. In HFmrEF, biomarker interactions were both related to inflammation and cardiac stretch. In HFpEF and HFmrEF (but not in HFrEF), remodeling markers at admission and changes in levels of inflammatory markers across the first 24 h were predictive for all-cause mortality and rehospitalization at 60 days (pinteraction &lt;0.05). CONCLUSIONS: Biomarker profiles in patients with acute HFrEF were mainly related to cardiac stretch and in HFpEF related to inflammation. Patients with HFmrEF showed an intermediate biomarker profile with biomarker interactions between both cardiac stretch and inflammation markers. (PROTECT-1: A Study of the Selective A1 Adenosine Receptor Antagonist KW-3902 for Patients Hospitalized With Acute HF and Volume Overload to Assess Treatment Effect on Congestion and Renal Function; NCT00328692)

Serum potassium levels and outcome in acute heart failure (data from the PROTECT and COACH trials)

Serum potassium is routinely measured at admission for acute heart failure (AHF), but information on association with clinical variables and prognosis is limited. Potassium measurements at admission were available in 1,867 patients with AHF in the original cohort of 2,033 patients included in the Patients Hospitalized with acute heart failure and Volume Overload to Assess Treatment Effect on Congestion and Renal FuncTion trial. Patients were grouped according to low potassium (&lt;3.5 mEq/l), normal potassium (3.5 to 5.0 mEq/l), and high potassium (&gt;5.0 mEq/l) levels. Results were verified in a validation cohort of 1,023 patients. Mean age of patients was 71 – 11 years, and 66% were men. Low potassium was present in 115 patients (6%), normal potassium in 1,576 (84%), and high potassium in 176 (9%). Potassium levels increased during hospitalization (0.18 – 0.69 mEq/l). Patients with high potassium more often used angiotensin-converting enzyme inhibitors and mineralocorticoid receptor antagonists before admission, had impaired baseline renal function and a better diuretic response (p [ 0.005), independent of mineralocorticoid receptor antagonist usage. During 180-day follow-up, a total of 330 patients (18%) died. Potassium levels at admission showed a univariate linear association with mortality (hazard ratio [log] 2.36, 95% confidence interval 1.07 to 5.23; p [ 0.034) but not after multivariate adjustment. Changes of potassium levels during hospitalization or potassium levels at discharge were not associated with outcome after multivariate analysis. Results in the validation cohort were similar to the index cohort. In conclusion, high potassium levels at admission are associated with an impaired renal function but a better diuretic response. Changes in potassium levels are common, and overall levels increase during hospitalization. In conclusion, potassium levels at admission or its change during hospitalization are not associated with mortality after multivariate adjustment

A network analysis to identify pathophysiological pathways distinguishing ischaemic from non-ischaemic heart failure

Aims Heart failure (HF) is frequently caused by an ischaemic event (e.g. myocardial infarction) but might also be caused by a primary disease of the myocardium (cardiomyopathy). In order to identify targeted therapies specific for either ischaemic or non‐ischaemic HF, it is important to better understand differences in underlying molecular mechanisms. Methods and results We performed a biological physical protein–protein interaction network analysis to identify pathophysiological pathways distinguishing ischaemic from non‐ischaemic HF. First, differentially expressed plasma protein biomarkers were identified in 1160 patients enrolled in the BIOSTAT‐CHF study, 715 of whom had ischaemic HF and 445 had non‐ischaemic HF. Second, we constructed an enriched physical protein–protein interaction network, followed by a pathway over‐representation analysis. Finally, we identified key network proteins. Data were validated in an independent HF cohort comprised of 765 ischaemic and 100 non‐ischaemic HF patients. We found 21/92 proteins to be up‐regulated and 2/92 down‐regulated in ischaemic relative to non‐ischaemic HF patients. An enriched network of 18 proteins that were specific for ischaemic heart disease yielded six pathways, which are related to inflammation, endothelial dysfunction superoxide production, coagulation, and atherosclerosis. We identified five key network proteins: acid phosphatase 5, epidermal growth factor receptor, insulin‐like growth factor binding protein‐1, plasminogen activator urokinase receptor, and secreted phosphoprotein 1. Similar results were observed in the independent validation cohort. Conclusions Pathophysiological pathways distinguishing patients with ischaemic HF from those with non‐ischaemic HF were related to inflammation, endothelial dysfunction superoxide production, coagulation, and atherosclerosis. The five key pathway proteins identified are potential treatment targets specifically for patients with ischaemic HF

Genetic Risk and Atrial Fibrillation in Patients with Heart Failure

Aims: To study the association between an atrial fibrillation (AF) genetic risk score with prevalent AF and all-cause mortality in patients with heart failure. Methods and results: An AF genetic risk score was calculated in 3759 European ancestry individuals (1783 with sinus rhythm, 1976 with AF) from the BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) by summing 97 single nucleotide polymorphism (SNP) alleles (ranging from 0–2) weighted by the natural logarithm of the relative SNP risk from the latest AF genome-wide association study. Further, we assessed AF risk variance explained by additive SNP variation, and performance of clinical or genetic risk factors, and the combination in classifying AF prevalence. AF was classified as AF or atrial flutter (AFL) at baseline electrocardiogram and/or a history of AF or AFL. The genetic risk score was associated with AF after multivariable adjustment. Odds ratio for AF prevalence per 1-unit increase genetic risk score was 2.12 (95% confidence interval 1.84–2.45, P = 2.15 × 10−24) in the total cohort, 2.08 (1.72–2.50, P = 1.30 × 10−14) in heart failure with reduced ejection fraction (HFrEF) and 2.02 (1.37–2.99, P = 4.37 × 10−4) in heart failure with preserved ejection fraction (HFpEF). AF-associated loci explained 22.9% of overall AF SNP heritability. Addition of the genetic risk score to clinical risk factors increased the C-index by 2.2% to 0.721. Conclusions: The AF genetic risk score was associated with increased AF prevalence in HFrEF and HFpEF. Genetic variation accounted for 22.9% of overall AF SNP heritability. Addition of genetic risk to clinical risk improved model performance in classifying AF prevalence