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.

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: 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 VO2 (weighted mean difference [WMD]: 0.521 ml min-1 kg-1, [95% CI] = - 0.7 to 1.8, Pfixed = 0.412) or LVEF (WMD: - 1.129%, [95% CI] = - 3.8 to 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 that the addition of resistance exercise does not inhibit aerobic adaptations in HF.

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 ß-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.

Cardiac energetics in patients with chronic heart failure and iron deficiency: an in-vivo 31 P magnetic resonance spectroscopy study.

AIMS: Iron deficiency (ID) is prevalent and adverse in chronic heart failure (CHF) but few human studies have explored the myocardial mechanism(s) that potentially underlie this adversity. Because mitochondrial oxidative phosphorylation (OXPHOS) provides over 90% of the hearts adenosine triphosphate (ATP), and iron is critical for OXPHOS, we hypothesized that patients with CHF and ID would harbour greater cardiac energetic impairments than patients without ID. METHODS AND RESULTS: Phosphorus magnetic resonance spectroscopy was used to quantify the phosphocreatine (PCr) to ATP (PCr/ATP) ratio, an index of in-vivo cardiac energetics, in CHF patients and healthy volunteers. Cardiac structure and function was assessed from magnetic resonance short stack cines. Patients with (n = 27) and without (n = 12) ID, and healthy volunteers (n = 11), were similar with respect to age and gender. The PCr/ATP ratio was lower in patients with ID (1.03 [0.83-1.38]) compared to those without ID (1.72 [1.51-2.26], p < 0.01) and healthy volunteers (1.39 [1.10-3.68], p < 0.05). This was despite no difference in cardiac structure and function between patients with and without ID, and despite adjustment for the presence of anaemia, haemoglobin levels, cardiac rhythm, or New York Heart Association (NYHA) class. In the total CHF cohort, the PCr/ATP ratio correlated with ferritin levels (rho = 0.4, p < 0.01), and was higher in NYHA class I than class II or III patients (p = 0.02). CONCLUSION: Iron deficiency is associated with greater cardiac energetic impairment in patients with CHF irrespective of anaemia and cardiac structure and function. Suppression of cardiac mitochondrial function might therefore be a mechanism via which ID worsens human CHF.

COVID-19 vaccination in patients with heart failure: a position paper of the Heart Failure Association of the European Society of Cardiology.

Patients with heart failure (HF) who contract SARS-CoV-2 infection are at a higher risk of cardiovascular and non-cardiovascular morbidity and mortality. Regardless of therapeutic attempts in COVID-19, vaccination remains the most promising global approach at present for controlling this disease. There are several concerns and misconceptions regarding the clinical indications, optimal mode of delivery, safety and efficacy of COVID-19 vaccines for patients with HF. This document provides guidance to all healthcare professionals regarding the implementation of a COVID-19 vaccination scheme in patients with HF. COVID-19 vaccination is indicated in all patients with HF, including those who are immunocompromised (e.g. after heart transplantation receiving immunosuppressive therapy) and with frailty syndrome. It is preferable to vaccinate against COVID-19 patients with HF in an optimal clinical state, which would include clinical stability, adequate hydration and nutrition, optimized treatment of HF and other comorbidities (including iron deficiency), but corrective measures should not be allowed to delay vaccination. Patients with HF who have been vaccinated against COVID-19 need to continue precautionary measures, including the use of facemasks, hand hygiene and social distancing. Knowledge on strategies preventing SARS-CoV-2 infection (including the COVID-19 vaccination) should be included in the comprehensive educational programmes delivered to patients with HF.

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.

Successful Identification of and Discrimination Between Atrial and Ventricular Arrhythmia with the Aid of Pacing and Defibrillator Devices.

The presence of supraventricular tachycardia is the leading cause of inappropriate shock in ICD recipients, and it can be a significant cause of morbidity, psychological distress and worsened clinical outcome. Modern pacing and ICD systems offer a number of discriminators that are integrated into algorithms to differentiate sustained ventricular tachycardia from supraventricular tachycardia. These algorithms can be adapted and optimised for each individual patient to ensure that only those arrhythmias that need treatment through the use of an ICD, are actually treated. This review summarises the single- and dual-chamber discriminators that can be used in the detection and classification of tachyarrhythmias.

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 < 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 > -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.

Calculated plasma volume status and outcomes in patients undergoing coronary bypass graft surgery.

OBJECTIVES: Congestion is associated with worse outcomes in critically ill surgical patients but can be difficult to quantify noninvasively. We hypothesised that plasma volume status (PVS), estimated preoperatively using a validated formula that enumerates percentage change from ideal plasma volume (PV), would provide incremental prognostic utility after coronary artery bypass graft (CABG) surgery. METHODS: In this retrospective cohort study, patients who underwent CABG surgery (1999-2010) were identified from a prospectively collected database. Actual ([1-haematocrit] x [a+(b x weight [kg])]) and ideal (c x weight [kg]) PV were obtained from equations where a, b and c are sex-dependent constants. Calculated PVS was then derived (100% x [(actual-ideal)/ideal]). RESULTS: In 1887 patients (mean age 67±10 years; 79% male; median European System for Cardiac Operative Risk Evaluation [EuroSCORE] 4), mean PVS was -8.2±9%. While 8% of subjects had clinical evidence of congestion, a relatively increased PV (PVS >0%) was estimated in 17% and correlated with lower serum sodium, higher EuroSCORE and a diagnosis of diabetes mellitus. A PVS≥5.6% was optimally prognostic and associated with greater mortality (HR: 2.31, p=0.009), independently of, and incremental to, EuroSCORE, New York Heart Association class and serum sodium. A PVS≥5.6% also independently predicted longer intensive care (ß: 0.65, p=0.007) and hospital (ß: 2.01, p=0.006) stays, and greater postoperative renal (OR: 1.61, p=0.008) and arrhythmic (OR: 1.29, p=0.03) complications. CONCLUSIONS: Higher PVS values, calculated simply from weight and haematocrit, are associated with worse inpatient outcomes after CABG. PVS could help refine risk stratification and further investigations are warranted to evaluate the potential clinical utility of PVS-guided management in patients undergoing CABG.

Physiological Reduction in Left Ventricular Contractile Function in Healthy Postpartum Women: Potential Overlap with Peripartum Cardiomyopathy.

AIMS: Peripartum cardiomyopathy is a potentially life-threatening cause of heart failure, commoner in Afro-Caribbean than Caucasian women. Its diagnosis can be challenging due to physiological changes in cardiac function that also occur in healthy women during the early postpartum period. This study aimed to (i) establish the overlap between normal cardiac physiology in the immediate postpartum period and pathological changes in peripartum cardiomyopathy ii) identify any ethnicity-specific changes in cardiac function and cardiac biomarkers in healthy postpartum women. METHODS AND RESULTS: We conducted a cross-sectional study of 58 healthy postpartum women within 48 hours of delivery and 18 matched non-pregnant controls. Participants underwent cardiac assessment by echocardiography and strain analysis, including 3D echocardiography in 40 postpartum women. Results were compared with 12 retrospectively studied peripartum cardiomyopathy patients. Healthy postpartum women had significantly higher left ventricular volumes and mass, and lower ejection fraction and global longitudinal strain than non-pregnant controls. These parameters were significantly more impaired in peripartum cardiomyopathy patients but with overlapping ranges of values. Healthy postpartum women had higher levels of adrenomedullin, placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt1) compared to controls. The postpartum state, adrenomedullin, sFlt1 and the sFlt1:PlGF ratio were independent predictors of LV remodelling and function in healthy postpartum women. CONCLUSION: Healthy postpartum women demonstrate several echocardiographic indicators of left ventricular remodelling and reduced function, which are associated with altered levels of angiogenic and cardiac biomarkers.

Osteopontin expression profiles predict pathological and clinical outcome in breast cancer.

BACKGROUND: Osteopontin (OPN) overexpression in breast cancer has been associated with adverse pathological and clinical outcomes. In this study, the OPN expression profiles were examined in a cohort of breast cancer patients. PATIENTS AND METHODS: RNA extraction and reverse transcription were performed on breast carcinomas (n = 127) and normal tissues (n = 33). Transcript levels were determined using real-time PCR. RESULTS: The OPN-a levels decreased with increasing TNM stage and worse clinical outcome. The OPN-b levels increased with tumour grade and Nottingham Prognostic Index (NPI) stage, were higher in patients who died of breast cancer than in those who were disease-free after 10 years and predicted disease-free survival. The OPN-c expression was associated with tumour grade and poor prognosis. Furthermore, the expression levels predicted local recurrence, disease-free survival and bone metastases. CONCLUSION: OPN expression profiles are significantly associated with tumour grade, stage and patient prognosis in breast cancer. OPN-c is likely to be of particular utility as a prognostic marker and should be included in future validation studies.