Exercise mode in heart failure: A systematic review and meta-analysis.

Background: Optimising exercise prescription in heart failure (HF) with a preserved (HFpEF) or reduced (HFrEF) ejection fraction is clinically important. As such, the aim of this meta-analysis was to compare traditional moderate intensity training (MIT) against combined aerobic and resistance training (CT) and high intensity interval training (HIIT) for improving aerobic capacity (VO2), as well as other clinically relevant parameters. Methods: A comprehensive systematic search was performed to identify randomised controlled trials published between 1990 and May 2021. Research trials reporting the effects of MIT against CT or HIIT on peak VO2 in HFpEF or HFrEF were considered. Left-ventricular ejection fraction (LVEF) and various markers of diastolic function were also analysed. Results: 17 studies were included in the final analysis, 4 of which compared MIT against CT and 13 compared MIT against HIIT. There were no significant differences between MIT and CT for peak VO2 (WMD:0.521ml·min-1·kg-1, [95% CI] =-0.7-1.8, Pfixed=0.412) or LVEF (WMD:-1.129 %, [95%CI] =-3.8-1.5,Pfixed=0.408). However, HIIT was significantly more effective than MIT at improving peak VO2 (WMD:1.62 ml·min-1·kg-1, [95%CI] =0.6-2.6,Prandom=0.002) and LVEF (WMD:3.24 %, [95%CI] =1.7-4.8,Prandom<0.001) in HF patients. When dichotomized by HF phenotype, HIIT remained significantly more effective than MIT in all analyses except for peak VO2 in HFpEF. Conclusions: HIIT is significantly more effective than MIT for improving peak VO2 and LVEF in HF patients. With the exception of peak VO2 in HFpEF, these findings remain consistent in both phenotypes. Separately, there is no difference in peak VO2 and LVEF change following MIT or CT, suggesting the addition of resistance exercise does not inhibit aerobic adaptations in HF

Exercise Mode in Heart Failure: A Systematic Review and Meta-Analysis

Background Optimising exercise prescription in heart failure (HF) with a preserved (HFpEF) or reduced (HFrEF) ejection fraction is clinically important. As such, the aim of this meta-analysis was to compare traditional moderate intensity training (MIT) against combined aerobic and resistance training (CT) and high-intensity interval training (HIIT) for improving aerobic capacity (VO 2 ), as well as other clinically relevant parameters. Methods A comprehensive systematic search was performed to identify randomised controlled trials published between 1990 and May 2021. Research trials reporting the effects of MIT against CT or HIIT on peak VO 2 in HFpEF or HFrEF were considered. Left-ventricular ejection fraction (LVEF) and various markers of diastolic function were also analysed. Results Seventeen studies were included in the final analysis, 4 of which compared MIT against CT and 13 compared MIT against HIIT. There were no significant differences between MIT and CT for peak VO 2 (weighted mean difference [WMD]: 0.521 ml min ⁻¹ kg ⁻¹ , [95% CI] = − 0.7 to 1.8, P fixed = 0.412) or LVEF (WMD: − 1.129%, [95% CI] = − 3.8 to 1.5, P fixed = 0.408). However, HIIT was significantly more effective than MIT at improving peak VO 2 (WMD: 1.62 ml min ⁻¹ kg ⁻¹ , [95% CI] = 0.6–2.6, P random = 0.002) and LVEF (WMD: 3.24%, [95% CI] = 1.7–4.8, P random < 0.001) in HF patients. When dichotomized by HF phenotype, HIIT remained significantly more effective than MIT in all analyses except for peak VO 2 in HFpEF. Conclusions HIIT is significantly more effective than MIT for improving peak VO 2 and LVEF in HF patients. With the exception of peak VO 2 in HFpEF, these findings remain consistent in both phenotypes. Separately, there is no difference in peak VO 2 and LVEF change following MIT or CT, suggesting that the addition of resistance exercise does not inhibit aerobic adaptations in HF

Progress in Cardiac Resynchronisation Therapy and Optimisation.

Cardiac resynchronisation therapy (CRT) has become the cornerstone of heart failure (HF) treatment. Despite the obvious benefit from this therapy, an estimated 30% of CRT patients do not respond ("non-responders"). The cause of "non-response" is multi-factorial and includes suboptimal device settings. To optimise CRT settings, echocardiography has been considered the gold standard but has limitations: it is user dependent and consumes time and resources. CRT proprietary algorithms have been developed to perform device optimisation efficiently and with limited resources. In this review, we discuss CRT optimisation including the various adopted proprietary algorithms and conduction system pacing

Multi-lead cephalic venous access and long-term performance of high-voltage leads.

BACKGROUND: Cardiac resynchronization therapy-defibrillator (CRT-D) implantation via the cephalic vein is feasible and safe. Recent evidence has suggested a higher implantable cardioverter-defibrillator (ICD) lead failure in multi-lead defibrillator therapy via the cephalic route. We evaluated the relationship between CRT-D implantation via the cephalic and ICD lead failure. METHODS: Data was collected from three CRT-D implanting centers between October 2008 and September 2017. In total 633 patients were included. Patient and lead characteristics with ICD lead failure were recorded. Comparison of "cephalic" (ICD lead via cephalic) versus "non-cephalic" (ICD lead via non-cephalic route) cohorts was performed. Kaplan-Meier survival and a Cox-regression analysis were applied to assess variables associated with lead failure. RESULTS: The cephalic and non-cephalic cohorts were equally male (81.9% vs. 78%; p = .26), similar in age (69.7 ± 11.5 vs. 68.7 ± 11.9; p = .33) and body mass index (BMI) (27.7 ± 5.1 vs. 27.1 ± 5.7; p = .33). Most ICD leads were implanted via the cephalic vein (73.5%) and patients had a mean of 2.9 ± 0.28 leads implanted via this route. The rate of ICD lead failure was low and statistically similar between both groups (0.36%/year vs. 0.13%/year; p = .12). Female gender was more common in the lead failure cohort than non-failure (55.6% vs. 17.9%, respectively; p = .004) as was hypertension (88.9% vs. 54.2%, respectively, p = .038). On multivariate Cox-regression, female sex (p = .008; HR, 7.12 [1.7-30.2]), and BMI (p = .047; HR, 1.12 [1.001-1.24]) were significantly associated with ICD lead failure. CONCLUSION: CRT-D implantation via the cephalic route is not significantly associated with premature ICD lead failure. Female gender and BMI are predictors of lead failure

Cardiopoietic cell therapy for advanced ischemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial

Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort

Management of Heart Failure in Patients with Chronic Kidney Disease.

Chronic kidney disease (CKD) is increasingly prevalent in patients with heart failure (HF) and HF is one of the leading causes of hospitalisation, morbidity and mortality in patients with impaired renal function. Currently, there is strong evidence to support the symptomatic and prognostic benefits of β-blockers, renin-angiotensin-aldosterone inhibitors (RAASis), angiotensin receptor-neprilysin inhibitors (ARNIs) and mineralocorticoid receptor antagonists (MRA) in patients with HF and CKD stages 1-3. However, ARNIs, RAASis and MRAs are often suboptimally prescribed for patients with CKD owing to concerns about hyperkalaemia and worsening renal function. There is growing evidence for the use of sodium-glucose co-transporter 2 inhibitors and IV iron therapy in the management of HF in patients with CKD. However, few studies have included patients with CKD stages 4-5 and patients receiving dialysis, limiting the assessment of the safety and efficacy of these therapies in advanced CKD. Interdisciplinary input from HF and renal specialists is required to provide integrated care for the growing number of patients with HF and CKD

Evidence of a tumour suppressive function E2F1 gene in human breast cancer

The E2F family of transcription factors are key regulators of genes involved in cell cycle progression, cell fate determination, DNA damage repair and apoptosis. E2F1 is unique in that it contributes both to the control of cellular proliferation and cellular death. Furthermore, unlike other E2Fs, E2F1 responds to various cellular stresses. This study aimed to examine the level of mRNA expression of E2F1 gene in normal and malignant breast tissue and correlate the level of expression to tumour stage. MATERIALS AND METHODS: One hundred and twenty-seven breast cancer tissue and 33 normal tissues were analyzed. Levels of transcription of E2F1 were determined using real-time quantitative PCR, normalized against CK19. Levels of expression were analyzed against TNM stage, nodal involvement, tumour grade and distant metastasis. RESULTS: The levels of E2F1 mRNA were lower in malignant tissues. They declined further with increasing TNM stage. This became statistically significant when TNM stages 3 and 4 were compared to TNM stages 1 and 2 disease (TNM1 vs. TNM3 p = 0.032; TNM1 vs. TNM4 p = 0.032; TNM2 vs. TNM3 p = .019; TNM2 vs. TNM4 p = 0.021). The levels of E2F1 also fell with increasing tumour grade, when comparing grade 2 and 3 with grade 1, however, the differences were not statistically significant. CONCLUSION: These results are highly suggestive of the role of E2F1 as a tumour suppressive gene in human breast cancer

Evidence of a tumour suppressive function of E2F1 gene in human breast cancer

Background: The E2F family of transcription factors are key regulators of genes involved in cell cycle progression, cell fate determination, DNA damage repair and apoptosis. E2F1 is unique in that it contributes both to the control of cellular proliferation and cellular death. Furthermore, unlike other E2Fs, E2F1 responds to various cellular stresses. This study aimed to examine the level of mRNA expression of E2F1 gene in normal and malignant breast tissue and correlate the level of expression to tumour stage. Materials and Methods: One hundred and twenty-seven breast cancer tissue and 33 normal tissues were analyzed. Levels of transcription of E2F1 were determined using real-time quantitative PCR, normalized against CK19. Levels of expression were analyzed against TNM stage, nodal involvement, tumour grade and distant metastasis. Results: The levels of E2F1 mRNA were lower in malignant tissues. They declined further with increasing TNM stage. This became statistically significant when TNM stages 3 and 4 were compared to TNM stages 1 and 2 disease (TNM1 vs. TNM3 p=0.032; TNM1 vs. TNM4 p=0.032; TNM2 vs. TNM3 p=0.019; TNM2 vs. TNM4 p=0.021). The levels of E2F1 also fell with increasing tumour grade, when comparing grade 2 and 3 with grade 1, however, the differences were not statistically significant. Conclusion: These results are highly suggestive of the role of E2F1 as a tumour suppressive gene in human breast cancer

Effect of ferric carboxymaltose on calculated plasma volume status and clinical congestion: a FAIR-HF substudy

Aims: Iron deficiency worsens symptoms, quality of life, and exercise capacity in chronic heart failure (CHF) and might do so by promoting fluid retention. We assessed whether iron repletion improved congestion in CHF and appraised the prognostic utility of calculated plasma volume status (PVS), a novel index of congestion, in the FAIR-HF data set. Methods and results: In FAIR-HF, 459 iron deficient CHF patients were randomized to intravenous ferric carboxymaltose (FCM) or saline and assessed at 4, 12, and 24 weeks. Using weight and haematocrit, we calculated PVS in 436 patients. At baseline, PVS and weight were −5.5 ± 7.7% and 76.9 ± 14.3 kg, with peripheral oedema evident in 35% of subjects. Higher PVS values correlated to other congestion surrogates such as lower serum albumin. At 4 weeks, FCM was associated with greater reductions in weight (0.02) and PVS (P &lt; 0.0001), and a trend for improved peripheral oedema at 24 weeks (0.07). Irrespective of treatment allocation, patients with a decrease in PVS from baseline to week 24 had higher increments in 6 min walking distance (61.4 m vs. 43.5 m, 0.02) and were more likely to improve their NYHA class (33.3% vs. 15.5%, 0.001). A PVS &gt; −4% at baseline predicted worse outcomes even after adjustment for treatment assignment (hazard ratio 1.88, 95% confidence interval 1.01–3.51, 0.046). Conclusions: Intravenous iron therapy with FCM is associated with early reductions in PVS and weight, implying that decongestion might be one mechanism via which iron repletion aids CHF patients. Calculated PVS is of prognostic utility in this cohort. © 2019 The Authors. ESC Heart Failure published by John Wiley &amp; Sons Ltd on behalf of the European Society of Cardiology