Aerobic exercise effect on prognostic markers for systolic heart failure patients: a systematic review and meta-analysis

From previous systematic reviews and meta-analyses, there is consensus about the positive effect of exercise training on exercise capacity for systolic heart failure (HF); however, the effect on actual prognostic markers such as NTproBNP and minute ventilation/carbon dioxide production (VE/VCO₂) slope has not been evaluated. The primary aim of the proposed study is to determine the effect of aerobic exercise training (AEX) on the VE/VCO₂ slope and NTproBNP. The following databases (up to February 30, 2013) were searched with no language limitations: CENTRAL (The Cochrane Library 2013, issue 2), MEDLINE (from January 1966), EMBASE (from January 1980), and Physiotherapy Evidence Database (PEDro) (from January 1929). We screened reference lists of articles and also conducted an extensive hand search of the literature. Randomized controlled trials of exercise-based interventions with 2-month follow-up or longer compared to usual medical care or placebo were included. The study population comprised adults aged between 18 and 65 years, with evidence of chronic systolic heart failure (LVEF < 45 % and baseline NTproBNP > 300 pg/ml). Two review authors independently extracted data on study design, participants, interventions, and outcomes. We assessed the risk of bias using PEDro scale. We calculated mean differences (MD) or standardized mean differences between intervention and control groups for outcomes with sufficient data; for other outcomes, we described findings from individual studies. Eight studies involving a total of 408 participants met the inclusion criteria across the NTproBNP (5 studies with 191 patients) and VE/VCO₂ slope (4 studies with 217 patients). Aerobic exercise significantly improved NTproBNP by a MD of ?817.75 [95 % confidence interval (CI) ?929.31 to ?706.19]. Mean differences across VE/VCO₂ slope were ?6.55 (95 % CI ?7.24 to ?5.87). Those patients’ characteristics and exercise were similar (frequency = 3–5 times/week; duration = 20–50 min/day; intensity = 60–80 % of VO₂ peak) on the included studies. Moreover, the risk of bias across all studies was homogeneous (PEDro scale = 7–8 points). However, based on the statistical analysis, the heterogeneity among the studies was still high, which is related to the variable characteristics of the studies. Aerobic exercise may be effective at improving NTproBNP and the VE/VCO₂ slope in systolic HF patients, but these effects are limited to a specific HF population meeting specific inclusion criterion in a limited number of studies. Future randomized controlled studies including diastolic and HF overleap with pulmonary diseases are needed to better understand the exact influence of AEX.     

Exercise therapy and autonomic function in heart failure patients: a systematic review and meta-analysis

A large body of evidence exists indicating that autonomic imbalance is characteristic of heart failure, with several parameters of autonomic function associated with adverse clinical outcomes. The aim of this systematic review and meta-analysis was to investigate the effects of exercise training on parameters of autonomic function in patients with heart failure and where possible quantify the size of the effect. We conducted database searches (PubMed, EMBASE and Cochrane Trials Register to 31 March 2017) for exercise-based rehabilitation trials in heart failure; using search terms, exercise training, autonomic function, heart rate recovery, heart rate variability and muscle sympathetic nerve activity. Pooled data indicated a statistically significant increase in heart rate recovery at 1 min (HRR₁) in exercise compared to control groups_, mean difference 5.90 bpm (95%CI 5.12, 6.69; p?<?0.00001). Pooled data also indicated that exercise training improved the short-term heart rate variability (HRV) parameters of root mean square of successive differences between normal heart beats (RMSSD (ms)) [mean difference 10.44 (95%CI 0.60, 20.28, p?=?0.04)] and high-frequency normalised units (HF_nu) [mean difference 7.72 (95%CI 3.32, 12.12, p?=?0.0006), which are predominantly reflective of parasympathetic activity. Analyses also indicated a statistically significant decrease in muscle sympathetic nerve activity (MSNA) bursts/minute (mean difference ??11.09 (95%CI ??16.18, ??6.00; p?<?0.0001) and MSNA bursts/100 heart beats (mean difference ??15.44 (95%CI ??20.95, ?9.92; p?<?0.00001) in exercise groups compared to controls. With improvements in HRR, HRV and MSNA, exercise training appears to facilitate an improvement in parasympathetic tone and reduction in sympathetic activity.     

The impact of exercise training for chronic heart failure patients with cardiac resynchronization therapy: A systematic review and meta-analysis

Background and objective:Systematically review the current published literature on the impact of exercise training (ET) in chronic heart failure (CHF) patients who were conducted cardiac resynchronization therapy (CRT).Methods:PubMed, EMBASE, and the Cochrane Library of Controlled Trails databases were searched for trials comparing the additional effects of ET in CHF patients after CRT implantation with no exercise or usual care control up until 2020.03.07. We independently screened the literature, extracted data, employed the tool for the assEssment of Study qualiTy and reporting in EXercise (TESTEX) to evaluate study quality and risk of bias, and performed meta-analysis with Revman 5.3 software.Results:Eight trials were identified for qualitative analysis and 7 randomized controlled trails (RCTs) included 235 participants (120 ET; 115 controls) for quantitative analysis. The results showed that the maximal workload (mean difference [MD] 26.32 W, 95% CI 19.41–33.23; P < .00001, I² = 0%) and the exercise duration (MD 68.95 seconds, 95% CI 15.41–122.48; P = .01, I² = 76%) had significant improvement in the ET group versus control. Subgroup analysis showed that compared with control, the change in peak oxygen uptake (VO₂) (MD 3.05 ml/kg/minute, 95% CI 2.53–3.56; P < .00001, I² = 0%), left ventricular ejection fraction (LVEF) (MD 4.97%, 95% CI 1.44–8.49; P = .006, I² = 59%), and health related quality of life (HRQoL) (the change in Minnesota living with heart failure questionnaire [MLHFQ]: MD −19.96, 95% CI −21.57 to −18.34; P < .00001, I² = 0%) were significantly improved in the light to moderate intensity training (non-HIT) group, while there seemed no statistical difference of above endpoints in the high intensity training (HIT) group.Conclusion:During the short term (up to 6 months), non-HIT could improve exercise capacity, cardiac function, and HRQoL in CHF patients with CRT. However, due to the small number of participants, a high-quality large-sample multicenter trial is demanded.     

Cardiac resynchronisation for patients with heart failure due to left ventricular systolic dysfunction -- a systematic review and meta-analysis

BACKGROUND: Randomised controlled trials generally suggest that cardiac resynchronisation improves outcomes in patients with heart failure due to left ventricular systolic dysfunction and cardiac dyssynchrony. Our objective was to provide a valid synthesis of the effects of CRT on mortality, major morbidity, quality of life and implantation success rates. METHODS: Systematic overview and meta-analysis of randomised trials, both blinded and open, comparing cardiac resynchronisation with control. The primary outcome was all-cause mortality, and secondary outcomes included hospitalisation for worsening heart failure, quality of life and implantation success rates. RESULTS: We identified 8 randomised trials which included 3380 patients and observed a total of 524 deaths. Follow-up ranged from 1 month to a mean of 29.4 months. Most trials were of high quality, with centrally administered randomisation and few patients lost to follow-up. CRT reduced mortality in these trials (odds ratio 0.72, 95% CI 0.59 to 0.88). In addition CRT reduced hospitalisation for worsening heart failure (odds ratio 0.55, 95% CI 0.44 to 0.68) and improved quality of life as measured by the Minnesota Living with Heart Failure Questionnaire (weighted mean difference -7.1, 95% CI -2.9 to -11.4). Implantation success rates in the trials were 87% or greater. CONCLUSION: Cardiac resynchronisation in patients with heart failure characterised by dyssynchrony substantially reduces all-cause mortality, major morbidity and improves quality of life.     

舒张性心力衰竭与收缩性心力衰竭临床特征的比较

目的:探讨舒张性心力衰竭和收缩性心力衰竭患者临床特征的差异。方法:选择心力衰竭患者253例,其中舒张性心力衰竭118例,收缩性心力衰竭135例。登记患者的临床资料,分析各组患者临床特征的差异。所有患者均检测N末端脑钠尿肽前体(NT-proBNP)及高敏C反应蛋白(hs-CRP)。结果:舒张性心力衰竭和收缩性心力衰竭均以老年患者居多,前者以女性多见(56.8%),并发高血压病(81.4%)及心房颤动(26.3%)均高于于后者(前项P0.01,后项P0.05),并发冠心病(45.8%)少于后者(P0.01);两组NT-proBNP及hs-CRP均随着NYHA心功能分级增加而显著升高(P0.01),舒张性心力衰竭组NT-proBNP低于收缩性心力衰竭组(P0.01),但hs-CRP两组间差异无统计学意义。结论:与收缩性心力衰竭相比,舒张性心力衰竭于老年女性更多见,高血压病患病率及心房颤动发生率较高,NT-proBNP水平较低。     

Cardiac resynchronization therapy in patients with mild heart failure: a systematic review and meta-analysis

Purpose  

Cardiac resynchronization therapy (CRT) reduces symptoms and improves survival in patients with advanced heart failure (New York Heart Association (NYHA) functional class III–IV), reduced ejection fraction, and wide QRS complex. Whether CRT has the same benefit also in asymptomatic or mildly symptomatic heart failure patients is controversial. Our objective is to summarize the available evidence on the effects of CRT in asymptomatic or mildly symptomatic (NYHA I–II) heart failure patients.     

Worsening renal function and prognosis in heart failure: systematic review and meta-analysis

BackgroundRenal impairment is associated with increased mortality in heart failure (HF). Recently, reports suggest that worsening renal function (WRF) is another predictor of clinical outcome in HF. The present study was designed to establish the proportion of patients with HF that exhibits (WRF) and the associated risk for mortality and hospitalization by conducting a systematic review and meta-analysis.Methods and ResultsA systematic search of MEDLINE revealed 8 studies on the relationship between WRF and mortality in 18,634 patients with HF. The mortality risk associated with WRF was estimated using random-effects meta-analysis. WRF was defined as an increase in serum creatinine ≥0.2 mg/dL or a corresponding decrease in estimated glomerular filtration rate ≥5 mL·min·1.73 m². Subgroup analysis included differentiation between in- and out-hospital patients, degree of WRF and time until end point occurrence. WRF developed in 4,734 (25%) patients and was associated with a higher risk for mortality (odds ratio [OR] = 1.62; 95% confidence interval [CI] 1.45–1.82, P < .001) and hospitalization (OR = 1.30, 95% CI 1.04–1.62, P = .022). The severity of WRF was also associated with greater mortality. Patients with impaired renal function at baseline were more prone to progressive renal function loss.ConclusionsWRF predicts substantially higher rates of mortality and hospitalization in patients with HF.     

Elevated homocysteine levels in patients with heart failure: A systematic review and meta-analysis

Background:Elevated homocysteine (Hcy) levels showed increasing significance as the predisposing factor for the pathogenesis of atherosclerotic sequelae, including cardiovascular mortality, coronary artery disease, and stroke. There is increasing evidence linking plasma Hcy levels and heart failure (HF). The association between the elevated level of plasma Hcy and HF was examined by meta-analysis and systematic review in this study.Methods:The PubMed and ScienceDirect databases until April 2020 were utilized to collect previous literature on plasma Hcy levels and the potential relation to HF. The pooled effects were evaluated depending on standardized mean differences (SMDs) with 95% confidence intervals (CIs), and the calculation was performed using Stata 12 software. Potential sources of heterogeneity were assessed with subgroup analysis and sensitivity analysis.Results:A total of 12 research projects including 5506 subjects were selected. For pooled effect, the results confirmed that patients with HF had higher Hcy levels than the control subjects (SMD,1.148 and 95%CI, [0.715, 1.581]). Based on the classification of New York Heart Association (NYHA), the Hcy levels for the group of NYHA I or II (SMD, 1.484 and 95% CI, [0.442, 2.527]) and the group of NYHA III or IV (SMD, 3.361 and 95% CI, [1.902, 4.820]) were significantly increased compared to controls, while the increase was more intensive for the group of NYHA III or IV. Subgroup analyses revealed similar results.Conclusion:Our meta-analysis identified that plasma Hcy levels were significantly elevated in HF patients compared to control subjects, which is positively related to the advancement of NYHA class.     

Ultrafiltration for patients with acute decompensated heart failure: A systematic review and meta-analysis

Background:Ultrafiltration plays an indispensable role in relieving congestion and fluid retention in patients with acute decompensated heart failure (ADHF) in recent years. So far, there is no consistent agreement about whether early ultrafiltration (UF) is a first-line treatment for patients with ADHF. We, therefore, conducted a meta-analysis to assess the efficacy and safety of UF.Methods:PubMed, Embase, and Cochrane Library databases were searched for randomized controlled trials (RCTs) that compared UF with diuretics in patients with ADHF and included our interested outcomes. The primary outcomes are heart failure rehospitalization, all-cause rehospitalization, and mortality. The second outcomes are fluid loss, weight loss, and adverse events. RevMan Version 5.4.1 was used to analyze the data of included studies.Results:A total of 12 studies with 1197 patients were included. Our results showed a reduction in heart failure rehospitalization (risk ratio [RR] 0.67, 95% confidence interval [CI]: 0.52–0.87, P = .003) and all-cause rehospitalization (RR 0.62, 95% CI: 0.42–0.92; P = .02), an increase in fluid loss (1.47 L, 95% CI: 0.95–1.99 L, P < .001) and weight loss (1.65 kg, 95% CI: 0.90–2.41 kg; P < .001). There was no difference in mortality (RR 1.09, 95% CI: 0.78–1.51; P = .62). There were inconsistent agreements about which group have more total adverse events. Subgroup analysis showed that UF with larger mean fluid-remove rate (≥200 mL/h) could significantly remove more fluid, lose more weight, and decrease heart failure rehospitalization. Less weight loss for patients with ADHF may correlated to higher percent of ischemic etiology (ischemic etiology ≥50%).Conclusion:Although UF is more effective in removing fluid than diuretics and decrease rehospitalization of heart failure and all causes, there is not enough evidence to prove that UF is superior because of adverse events and mortality in the UF group. The mean fluid-removal rates should be set to ≥200 mL/h. Patient with different etiology may have different effects when treated with UF and it is a weak conclusion.Trial registration: The systematic review was registered with the International Prospective Registry of Systematic Reviews. (https://www.crd.york.ac.uk/prospero/, registration number CRD42021245049).     

Intermittent levosimendan infusion in ambulatory patients with end-stage heart failure: a systematic review and meta-analysis of 984 patients

Heart Failure Reviews - We sought to synthesize the available evidence regarding safety and efficacy of intermittent levosimendan (LEVO) infusions in ambulatory patients with end-stage heart...     

Blunted hemodynamic response and reduced oxygen delivery with exercise in anemic heart failure patients with systolic dysfunction

Anemic heart failure patients with systolic dysfunction are known to have reduced exercise capacity. Whether this is related to poor hemodynamic adaptation to anemia is not known. Peak exercise oxygen consumption (VO2) and hemodynamics at rest and peak exercise were assessed among 209 patients and compared among those who were (n=90) and were not (n=119) anemic. Peak VO2 was significantly lower among anemic patients (11.7+/-3.3 mL/min/kg vs 13.4+/-3.1 mL/min/kg; P=.01). At rest, right atrial pressure was higher (10+/-5 mm Hg vs 8+/-4 mm Hg; P=.02) and venous oxygen saturation lower (62%+/-8% vs 58%+/-10%; P<.01) among anemic patients. At peak exercise, anemic patients had a higher wedge pressure (27+/-9 mm Hg vs 24+/-10 mm Hg; P=.04). No significant differences in stroke volume, cardiac index, systemic vascular resistance, or oxygen saturation were noted between the 2 groups. In conclusion, the relative hemodynamic response to exercise among anemic heart failure patients appears blunted and may contribute to worse exercise tolerance.     

NT‐pro‐BNP predicts worsening renal function in patients with chronic systolic heart failure

Background: Worsening renal function (WRF) is frequently observed in patients with heart failure and is associated with worse outcome. The aim of this study was to examine the association of the cardiac serum marker N‐terminal pro‐B‐type natriuretic peptide (NT‐pro‐BNP) and WRF. Methods: A total of 125 consecutive patients of a tertiary care outpatient clinic for heart failure prospectively underwent evaluation of renal function every 6 months. The association of baseline NT‐pro‐BNP with WRF was analysed during a follow up of 18 months. Results: Twenty‐eight (22.4%) patients developed WRF (increase in serum creatinine ≥0.3 mg/dL). Patients with WRF (2870 pg/mL, interquartile range (IQR) 1063–4765) had significantly higher baseline NT‐pro‐BNP values than patients without WRF (547 pg/mL, IQR 173–1454). The risk for WRF increased by 4.0 (95% CI 2.1–7.5) for each standard deviation of log NT‐pro‐BNP. In multivariable analysis including age, baseline renal function, ejection fraction, New York Heart Association class and diuretic dose, only NT‐pro‐BNP and diabetes were independent predictors of WRF. At a cut‐off level of 696 pg/mL, NT‐pro‐BNP showed a sensitivity of 92.9% and a negative predictive value of 96.4% for WRF. Conclusion: NT‐pro‐BNP is a strong independent predictor of WRF within 18 months in patients with systolic heart failure with a high negative predictive value. Further studies are needed to evaluate reno‐protective strategies in patients with elevated NT‐pro‐BNP.     

The treatment gap in patients with chronic systolic heart failure: a systematic review of evidence-based prescribing in practice

The extent and impact of under-prescribing of evidence-based pharmacological therapies among heart failure patients with reduced ejection fraction (HFREF) in contemporary practice is unclear. We sought to examine the prescribing patterns of angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), β-blockers (BBs) and mineralocorticoid receptor antagonists (MRAs), and to quantify the estimated ‘treatment gap’ among HFREF patients in the ‘real-world’ setting. The MEDLINE, PubMed, EMBASE, CINAHL and CENTRAL databases were searched for registry- or survey-based studies which examined the prescribing rates of ACE inhibitors, ARBs, BBs and MRAs among HFREF patients. Searches were limited to those published in the years 2000–2015. A total of 23 reports, including 83,605 patients, were evaluated. Overall, ACE inhibitors/ARBs, BBs and MRAs were prescribed to 79.8, 81.4 and 36.4 % of patients, respectively. The estimated treatment gaps in the overall population were 13.1 % for ACE inhibitors/ARBs, 3.9 % for BBs and 16.8 % for MRAs. The proportion of patients who received ≥50 % of the guideline-recommended target doses was 72 % for ACE inhibitors, 51 % for ARBs, 49 % for BBs, 53 % for the combination of ACE inhibitors/ARBs and BBs and 83 % for MRAs. Prescribing these drugs according to contemporary guidelines was associated with lower mortality risk. Patients who were elderly, female and with comorbidities were less likely to receive optimal treatment as recommended by the guidelines. ACE inhibitors, ARBs, BBs and MRAs are under-prescribed in eligible HFREF patients. Efforts should be made to improve approaches to closing the treatment gap at both systems of care and individual levels.