Survival In Chronic Heart Failure Patients Research Articles

Diagnostic and Prognostic Value of Plasma lncRNA SRA1 in Chronic Heart Failure.

The pathogenesis and development of chronic heart failure (CHF) may involve long non-coding ribonucleic acid (lncRNA) steroid receptor RNA activator 1 (SRA1), a known cardiomyopathy risk factor and regulator of cardiac myofibroblast activation. This study aimed to investigate the application of SRA1 in the early detection and prediction of CHF. SRA1 plasma expression was determined in CHF patients and healthy individuals/using real time-quantitative polymerase chain reaction (RT-qPCR). The diagnostic and prognostic value of SRA1 was assessed using receiver operating curve (ROC) and Cox regression analyses. Compared with the healthy controls, the patients with CHF had increased brain natriuretic peptide (BNP) levels, left atrial end-systolic diameter (LAD), left ventricular end-diastolic diameter (LVDd), and decreased left ventricular ejection fraction (LVEF). SRA1 was significantly upregulated in CHF patients as well as positively correlated with BNP level, LAD, and LVDd, and negatively correlated with LVEF. SRA1 could sensitively discriminate CHF patients from healthy individuals and was an independent predictor of adverse event-free survival in CHF patients. Upregulated plasma SRA1 can discriminate patients with CHF from healthy individuals and predict adverse outcomes in CHF patients. Thus, SRA1 is a potential molecular indicator for monitoring chronic heart failure development.

Downregulation of autophagy-related circular RNA (ACR) is correlated with poor survival of patients with chronic heart failure

ABSTRACT Autophagy‐related circular RNA (ACR) has been reported to protect myocardial tissues from injury and participate in chronic heart failure (CHF), while its role in CHF is unknown. This study aimed to study the role of ACR in CHF. ACR and miR-532 levels in CHF (ischemic-origin, n = 60) patients and healthy controls (n = 60) were analyzed by RT-qPCR. The prognostic value of ACR was analyzed by survival curve analysis. ACR was overexpressed in cardiomyocytes, and the effects of ACR overexpression on the expression of miR-532 and the methylation of miR-532 gene were analyzed using RT-qPCR and methylation-specific PCR (MSP). Cardiomyocyte apoptosis under hypoxic conditions was analyzed with cell apoptosis assay. It was observed that ACR expression was downregulated in CHF. Kaplan‑Meier and multivariate Cox regression analysis suggested that low ACR predicted overall survival of CHF patients and ACR was inversely correlated with miR-532 across plasma samples. In cardiomyocytes, ACR increased miR-532 gene methylation to decrease its expression. Cell apoptosis analysis showed that ACR overexpression reduced the enhancing effects of miR-532 overexpression on cardiomyocyte apoptosis under hypoxic conditions. Therefore, ACR is downregulated in CHF and may suppress hypoxia-induced cardiomyocytes by downregulating miR-532 via methylation.

COVID-19 and Heart Failure: The Big Challenge.

Patients with chronic heart failure (HF) are among the most vulnerable populations in the COVID era. HF patients infected with COVID-19 are at a significant risk of severe illness and death. They usually present with shortness of breath and radiologic signs of an acute decompensation, which can mask the manifestations of COVID-19. Delay in the diagnosis increases the risk of individual poor outcomes and jeopardizes healthcare workers if protective and isolation measures are not established promptly. Furthermore, the COVID-19 pandemic is forcing health-care systems to modify the delivery of care to patients. Outpatient services are being done virtually, and elective procedures postponed. These may have an impact on the quality of life and survival of chronic HF patients. We present two cases of patients with the previous history of HF who developed an acute exacerbation secondary to COVID-19 infection. In this review, we focused on the main challenges physicians face when dealing with COVID-19 in chronic HF patients at the individual and system levels.

Use of devices in elderly patients with chronic heart failure

Chronic heart failure (CHF) is a frequent and clinically relevant condition in elderly patients. Despite the improvements in medical therapy, CHF mortality is persistently high. The introduction into clinical practice of pacemakers for cardiac resynchronization therapy (CRT) and of implantable cardioverter-defibrillators (ICD) has significantly increased survival in CHF patients. In spite of clinical and epidemiological data, evidence of the effectiveness of these devices in the elderly is scant, and the few existing data derive from observational studies. Regarding CRT, in 1787 patients, the InSync/InSync ICD study showed no age-related differences in the prevalence of responders to therapy (about 60%) and in procedural complication rates (11%). Regarding ICD, in the 6311 patients enrolled in the Italian Clinical Service Project, 22.6% of the excess mortality observed in older subjects was due to comorbid conditions. Specific controlled clinical trials are needed to address the impact of CRT and ICD on health-related quality of life, disability and cognitive profile. The findings obtained will be useful to clarify clinical, ethical and cost-effectiveness issues in order to develop specific age-oriented guideline recommendations.

28 Heart Rate is not Related to Survival in Patients with Heart Failure and Atrial Fibrillation

<h3>Introduction</h3> Atrial fibrillation (AF) is common in patients with chronic heart failure (CHF), and is associated with significant morbidity and mortality. Although there is robust evidence that heart rate is a risk factor in CHF and that reducing elevated heart rates improves survival in patients who are in sinus rhythm, the importance of strict heart rate control in AF is still not clear. This study sought to investigate the influence of resting ventricular rate on survival in CHF, comparing those who are in sinus rhythm to those in AF. <h3>Methods</h3> A total of 1415 CHF patients (mean age 76+-11 years, 36% females, 65% IHD, 41% NYHA II, 44% NYHA III, 14% NYHA IV), of whom 62% (n = 875) were in sinus rhythm and 38% (n = 540) in permanent AF were evaluated from the BIOSTAT-CHF Scotland study. Patients from both in-patient and out-patient settings were included. We analysed the heart rate and rhythm data recorded on a 12 lead ECG at the baseline review. Multivariate Cox proportional hazards models and Kaplan-Meier curves were used to assess the influence of heart rate on survival in CHF patients with AF or sinus rhythm. <h3>Results</h3> During a median per-person follow-up of 1.5 yrs (QIR 0.7–2.2), there were 330 (23%) all-cause deaths. Although Kaplan-Meier survival curves displayed significant differences between the AF and sinus rhythm groups (log-rank test p = 0.014), multivariate Cox survival models showed no significant difference between the 2 groups (hazard ratio [HR]: 0.98, 95% CI: 0.75–1.29; p = 0.9). When assessing the influence of heart rate, multivariate Cox models showed that higher heart rates (per 10 beats/min increments) were associated with worse survival in patients in sinus rhythm (HR: 1.14, 95% CI: 1.03–1.25; p = 0.008), but not for those in AF (HR: 0.98, 95% CI: 0.91–1.07, p = 0.7), for both preserved and reduced ejection fraction heart failure. When separated into two categories (heart rate &lt;80bpm vs. ≥80 bpm), those in sinus rhythm with a heart rate ≥80 bpm had a significantly worse survival than those with a heart rate &lt;80 bpm (HR: 1.57, 95% CI: 1.10–2.23, p = 0.012). <h3>Conclusion</h3> Although higher heart rate was associated with worse survival for CHF patients in sinus rhythm, it does not appear to be associated with survival in those who are in AF. These findings question the value of strict heart rate control in CHF patients with atrial fibrillation, thus necessitating further research in this area.

CD4+CD28null cells are an independent predictor of mortality in patients with heart failure

AimsImmune activation and subsequent release of proinflammatory cytokines plays a central role in the pathophysiology of chronic heart failure (CHF). Cytotoxic CD4+CD28null cells are generated under inflammatory conditions and implicated in a variety of pathological processes like atherosclerosis and autoimmune diseases. The study aim was to assess the impact of CD4+CD28null cells on survival in CHF patients. Methods and resultsCirculating lymphocytes from 107 CHF patients were analyzed for the distribution of CD4 subsets by flow cytometry. During a median follow-up of 23 months, 22 (20%) persons died. CD4+CD28null cells independently predicted all-cause mortality with an adjusted hazard ratio (HR) of 1.88 per 1-standard deviation increase (95% confidence interval (CI): 1.26–2.79, P = 0.002) and with a HR of 1.83 for cardiovascular mortality (95% CI: 1.18–2.86, P = 0.008), respectively. Further, we found a significant association with NT-proBNP (r = 0.23). ConclusionCirculating CD4+CD28null cells are associated with CHF severity and are a strong and independent predictor of mortality in CHF fostering the implication of the immune system in CHF pathophysiology.

Abstract 9643: Effect of Partial Fatty Acids Oxidation Inhibition With Trimetazidine on Survival in Heart Failure: Results From an International Multicentre Retrospective Cohort Study

Background: Trimetazidine (TMZ) shifts myocardial energy production from free fatty acids to glucose oxidation, a more efficient metabolic pathway. Previous small studies in patients with chronic heart failure (CHF) have shown that TMZ can improve contractile left ventricular function, exercise capacity and NYHA class compared to placebo. However, no data on the effects of TMZ on survival in patients with CHF have ever been produced. Methods: In this international multicentre retrospective cohort study 669 patients (521 post-ischaemic) from the CHF clinics of our institutions were recruited. 362 patients (288 post-ischaemic) were on TMZ (20 mg tid or 35 mg bid) due to symptoms persistence (dyspnoea on exertion, fatigue, orthopnoea, oedema, alone or in combination) despite up titration of optimal CHF medical therapy, while the remaining patients continued conventional CHF therapy alone. Effects of TMZ administration were evaluated by Kaplan-Meier survival analysis and Cox-Regression survival analysis. Obtained results were corrected with propensity score (PS) in order to minimize selection bias. The protocol has been registered in the Italian Pharmaceutical Agency (AIFA) - Italian Ministry of Health, on the observational studies registry, ID number 458. Results: Kaplan-Meier analysis for global mortality showed 11•3% improved global survival (p=0•015) and 8•5% improved survival for death from cardiovascular disease (CVD) causes (p=0•050) in the TMZ group. Cox regression analysis for global mortality showed a significant risk reduction for TMZ treated patients with a PS-corrected hazard ratio (HR)= 0•189 (confidence interval - CI 95%: 0•079-0•454; p=0•0002). TMZ also showed a good risk reduction profile for CVD death causes (PS-adjusted HR=0•072, CI 95%: 0•019-0•268, p=0•0001). The rate of hospitalization for cardiovascular causes was reduced by 10.4% at 5 years (p &lt; 0•0005) with increased hospitalization-free survival of •8 months. Conclusions: TMZ is effective in reducing both global and cardiovascular mortality and event-free survival in patients with CHF. The addition of TMZ on top of optimal medical therapy improves long-term survival in CHF patients.

Effect of partial fatty acid oxidation inhibition with trimetazidine on mortality and morbidity in heart failure: Results from an international multicentre retrospective cohort study

ObjectivesThe aim of this cohort study was to retrospectively evaluate, in patients with chronic heart failure (CHF), the long term effect of trimetazidine (TMZ) on morbidity and mortality. BackgroundPrevious small studies in patients with CHF have shown that TMZ can improve left ventricular function, exercise capacity and NYHA class compared to placebo. However, no data on the effects of TMZ on survival in patients with CHF have ever been produced. MethodsIn this international multicentre retrospective cohort study data from 669 patients were analyzed. 362 patients were on TMZ due to symptom persistence despite up-titration of optimal CHF therapy, while the remaining patients continued conventional CHF therapy alone. Propensity score analysis was performed in order to minimize selection bias between the two groups. ResultsKaplan–Meier analysis for global mortality showed 11.3% improved global survival (p=0.015) and 8.5% improved survival for cardiovascular (CVD) death (p=0.050) in the TMZ group. Cox regression analysis for global mortality showed a significant risk reduction for TMZ treated patients with a hazard ratio (HR)=0.189 (confidence interval — CI 95%: 0.017–0.454; p=0.0002). TMZ also showed a good risk reduction profile for CVD death causes (HR=0.072, CI 95%: 0.019–0.268, p=0.0001). The rate of hospitalization for cardiovascular causes was reduced by 10.4% at 5years (p<0.0005) with increased hospitalization-free survival of 7.8months. ConclusionTMZ is effective in reducing mortality and event-free survival in patients with CHF. The addition of TMZ on top of optimal medical therapy improves long term survival in CHF patients.

THE PROBLEM OF THE QUALITY OF LIFE IN CHRONIC HEART FAILURE

Clinically manifested chronic heart failure (CHF) is associated with significant decrease of patients' qualityoflife(QL)caused by their functional capability as well as their psychoemotional discomfort. Most informative predictors of QL in CHF are its ischemic origin, age, female sex, NYHA functional class (FC), tachycardia at rest, creatinine clearance, Hb, uric acid and plasma cholesterol levels, moderate-to-severe depression. Data of Minnesota Heart Failure Life Quality/SF-36 questionnaires demonstrate high prognostic value in regard of 1 - 5 year survival in CHF patients with the same NYHA class and so may be useful in risk stratification of patients with comparable functional status.

Aspirin, clopidogrel, and warfarin use and outcomes in a cohort of 580 patients discharged after hospitalization for decompensated heart failure

The benefits of taking of aspirin, clopidogrel, and warfarin in relation to cardiovascular mortality and re-hospitalization in chronic heart failure (HF) patients have been called into question. We examined the outcomes (cardiac mortality and/or HF re-hospitalization) in patients discharged from our hospital between January 2003 and July 2009 after hospitalization for chronic decompensated HF. Of 580 HF patients (mean age, 63 ± 13 years; mean ejection fraction, 26 ± 9%, 63% with coronary disease and 37% without coronary disease), 207 patients (36%) died due to cardiovascular reasons, and 313 (54%) required HF re-hospitalization for decompensated HF during a 39 ± 14 month follow-up period. 101 (17%) patients were taking clopidogrel during enrollment in the study. When comparing patients who were on clopidogrel treatment with those who were not, clopidogrel was found to have a beneficial effect on cardiac mortality (27 vs. 38%, P = 0.04). In conclusion, in this observational prospective study, patients who used clopidogrel showed decreased cardiac mortality [HR, 0.566 (95% CI 0.332-0.964), P = 0.036] compared to patients who did not take clopidogrel. Clopidogrel had a beneficial effect on the survival of chronic HF patients in the long term.

The WHICH? trial: rationale and design of a pragmatic randomized, multicentre comparison of home‐ vs. clinic‐based management of chronic heart failure patients

To describe the rationale and design of the Which Heart failure Intervention is most Cost-effective & consumer friendly in reducing Hospital care (WHICH?) trial. WHICH? is a pragmatic, multicentre, randomized controlled trial that seeks to determine if multidisciplinary management of chronic heart failure (CHF) patients post-acute hospitalization delivered in a patient's own home is superior to care delivered via a specialist CHF outpatient clinic. The composite primary endpoint is all-cause, unplanned recurrent hospitalization or death during 12-18 months of follow-up. Of 688 eligible patients, 280 patients (73% male and 66% principal diagnosis of CHF) with a mean age of 71 ± 14 years have been randomized to home- (n = 143) or clinic-based (n = 137) post-discharge management. This will provide 80% power (two-sided alpha of 0.05) to detect a 15% absolute difference in both the primary end-point and rate of all-cause hospital stay. Preliminary data suggest that the two groups are well matched in nearly all baseline socio-economic and clinical parameters. The majority of patients have significant co-morbidity, including hypertension (63%), coronary artery disease (55%), and atrial fibrillation (53%) with an accordingly high Charlson Index of Comorbidity Score (6.1 ± 2.4). Despite its relatively small size, the WHICH? trial is well placed to examine the relative impact of two of the most commonly applied forms of face-to-face management designed to reduce recurrent hospitalization and prolong survival in CHF patients.

Independent and additive prognostic ability of serum carboxy-terminal telopeptide of collagen type-I in heart failure patients: a multi-marker approach with high-negative predictive value to rule out long-term adverse events

Altered myocardial extracellular matrix turnover has been proposed as a major determinant of myocardial remodelling. Carboxy-terminal telopeptide of collagen type-I (CITP) represents a collagen type-I degradation-derived serum peptide. In this study we examined the independent and additive prognostic value of serum concentrations of CITP compared with well-known mortality predictors such as the N-terminal pro-brain natriuretic peptide (NT-proBNP) in chronic heart failure (CHF) patients. We studied 196 consecutive patients (126 male, mean age 69 ± 10 years), who were admitted for acute decompensation of the CHF syndrome. The study entry point was determined at the discharge of the patients after achieving a stable compensated status. The primary endpoint was cardiac mortality during a 12-month follow-up. In the multivariate Cox proportional hazard model the levels of CITP remained a predictor of survival (hazards ratio 0.4 95% confidence interval 0.21-0.76, P = 0.005), independent of NT-proBNP levels. The stratified log-rank test (P < 0.001) showed that CHF patients characterized by low levels of both biomarkers had better survival (hazards ratio 0.12 95% confidence interval 0.04-0.35, P < 0.001) compared with patients characterized by high levels of both biomarkers. The negative predictive value of the combined measure for long-term adverse events was 94%. Serum levels of CITP were shown to be an independent and strong prognostic marker regarding survival in CHF patients. Furthermore, CITP levels had an additive prognostic value compared with NT-proBNP levels. These findings underline the detrimental role of myocardial fibrosis in the progression of heart failure and suggest a novel multi-marker approach for risk stratification in the CHF syndrome.

Restrictive pattern in spirometry as a predictor of poor survival in chronic heart failure patients on betaceptor-antagonist, with possible indications for heart transplantation

Restrictive spirometry pattern is commonly associated with chronic heart failure (CHF), but its prognostic value is poorly documented. Utility of Lower Limit of Normal (LLN)-based spirometry interpretation has not yet been evaluated in CHF patients. Impact of restrictive pattern defined according to classic or LLN criteria on prognosis in CHF patients was therefore addressed. 171 CHF patients on long-term beta-antagonist treatment with PeakVO2 >12 ml/kg/min (147 men, 49±9 years, LVEF 26±8%, 51% ischemic) were divided into groups based on their spirometry: Group 1A (N=129) - classic criteria: no restriction, Group 2A (N=12) - classic criteria: restrictive pattern, Group 1B (N=90) - LLN criteria: no restriction, Group 2B (N=26) - LLN criteria: restrictive pattern. PeakVO2 in the study groups equaled 12.1-19.9 ml/kg/min. Control group (N=30) - PeakVO2 >20 ml/kg/min, absence of restriction or obstruction (FEV1%FVC ≥70) defined by classic criteria. Classic criteria: VCin% <70 and FEV1%FVC ≥70. LLN criteria: VCin% <LLN and FEV1%FVC ≥LLN. LLN is the 5th percentile of spirometry values' normal distribution in the reference population. End-points: time to death, 1- and 2-year mortality, number and duration time of cardiac and all-cause hospitalizations. P<0.05 was considered significant. Significantly worse survival was observed in groups 2A and 2B when compared to the control group. One-year and 2-year mortality were significantly higher in group 2B (19.2 and 40.9%; control group: 0% and 0%, respectively) and 2-year mortality was higher in group 2A (40.0%). Restrictive spirometry pattern is associated with worse survival in CHF patients with PeakVO2 above the cutoff point for OHT listing. Use of LLN criteria may be useful to predict poor 1-year prognosis.

The growth hormone/insulin‐like growth factor‐I system in chronic heart failure and its interaction with adiponectin

The growth hormone/insulin‐like growth factor‐I system in chronic heart failure and its interaction with adiponectin

Atrial fibrillation ablation in systolic heart failure patients: a promising tool?

Atrial fibrillation (AF) is a significant factor complicating heart failure (HF). It is estimated that the prevalence of AF is as high as 50% of patients with NYHA class IV. The loss of atrial contribution to ventricular filling, non-physiological fast and irregular heart rate, and increased risk of thrombo-embolism are some of the adverse effects of AF in HF patients. Whether AF has an impact on survival in chronic HF patients is still a matter of debate. In the recently published AF-CHF trial, no difference was found in cardiovascular mortality between the two treatment strategies.1 Although antiarrhythmic therapy is currently considered the first-line therapy in AF patients, a recurrence of AF is a common event, with rates as high as 44–67% within 1 year after successful cardioversion.2 To date, antiarrhythmic drug therapy appears ineffective as a single strategy to maintain sinus rhythm (SR). Post hoc analyses have demonstrated that patients who remained in SR had better survival rates in both the AF-CHF and AFFIRM trials.3 There is evidence suggesting that patients with HF and AF have a worse prognosis than patients with HF and SR.4 The presence of HF has been identified as one of the … *Corresponding author. Tel: +49 9561 226348, Fax: +49 9561 226349, Email: brachmann.laptop{at}extern.klinikum-coburg.de

Undetected paroxysmal atrial fibrillation in chronic heart failure patients: is it clinically relevant to catch the atrial phantom?

Chronic heart failure (CHF) is frequently accompanied by atrial fibrillation (AF). How often AF occurs in CHF patients is difficult to know since many episodes come and go undetected because of lacking symptoms. Therefore, assessing the total burden of AF calls for continuous rhythm monitoring. At present, we do not know whether assessing burden of AF is clinically relevant. Furthermore, we do not know whether AF has any impact on survival in CHF patients, since previous clinical studies show conflicting results. Caldwell et al. 1 shed light on this issue by retrospectively studying cardiac resynchronization therapy device downloads in 162 patients with CHF in order to address two questions. First, what is the prevalence of asymptomatic paroxysmal AF (PAF) in CHF patients? Secondly, what is the subsequent effect on mortality, thrombo-embolism and all-cause hospitalizations? They defined AF as a mode-switch event with an atrial rate >200 bpm for a minimum of 30 s. Using medical records, patients were divided into four groups: (i) patients who remained in sinus rhythm (SR), (ii) patients in chronic AF, (iii) patients who were known to have paroxysmal AF (known PAF), and (iv) patients thought to be persistently in SR in whom episodes of AF were newly identified (new PAF). One quarter of patients developed new PAF but AF burden was low. During the mean follow-up period of 424 days, no statistically significant differences in outcome between the SR, new PAF, and known PAF patients were found. There was, however, a trend towards higher mortality in patients with new PAF which matches with an important observation in the Euro Heart Survey on AF in which patients with first documented AF had higher mortality than patients with known PAF or persistent AF.2 Similarly, Pozzoli et al. 3 showed that new onset AF in a previously … *Corresponding author. Tel: +31 43 387 50 93, Fax: +31 43 387 51 04, Email: hjgm.crijns{at}mumc.nl

Prognostic importance of elevated serum creatinine in chronic heart failure

Renal dysfunction(RD) is common in patients with chronic heart failure(CHF). However, its prognostic importance in Japanese CHF patients is still unclear. We sought to clarify characteristics and the prognosis of CHF patients with RD (Serum creatinine >1.0mg/dl) using our CHF registry called the Chronic Heart Failure Analysis and Registry in the Tohoku District. A total of 1,278 CHF patients were enrolled as of April 2004. The study populations were 132 CHF patients with RD and 390 CHF patients without RD from the registry. Patients with creatinine of >4.0 mg/dl were excluded. Following significant differences were observed in CHF patients with RD at the entry compared to CHF patients without RD; older patients(71.3 ± 12.1 vs 64.0 ± 14.5), more prevalent ischemic etiology(24.8% vs 14.9%), higher incidence of anemia(55.9% vs 33.0%), more symptomatic patients(NYHA-III/IV; 27.1% vs 15.0%), more complicated by diabetes(21.8% vs 13.8%), and higher BNP level (339.0 ± 481.0 vs 223.8 ± 290.6 pg/ml). The Kaplan-Meier analysis showed that the all-cause mortality rate and the admission rate due to congestive heart failure were significantly higher in CHF patients with RD (3-year all-cause mortality; 31.9% vs 12.0%). RD had a significant impact on the survival of CHF patients. Further investigations are necessary to improve the prognosis and QOL of CHF patients with RD.