Intravenous iron for heart failure, iron deficiency definitions, and clinical response: the IRONMAN trial.

BACKGROUND AND AIMS: What is the relationship between blood tests for iron deficiency, including anaemia, and the response to intravenous iron in patients with heart failure? METHODS: In the IRONMAN trial, 1137 patients with heart failure, ejection fraction ≤ 45%, and either serum ferritin < 100 µg/L or transferrin saturation (TSAT) < 20% were randomized to intravenous ferric derisomaltose (FDI) or usual care. Relationships were investigated between baseline anaemia severity, ferritin and TSAT, to changes in haemoglobin from baseline to 4 months, Minnesota Living with Heart Failure (MLwHF) score and 6-minute walk distance achieved at 4 months, and clinical events, including heart failure hospitalization (recurrent) or cardiovascular death. RESULTS: The rise in haemoglobin after administering FDI, adjusted for usual care, was greater for lower baseline TSAT (Pinteraction < .0001) and ferritin (Pinteraction = .028) and more severe anaemia (Pinteraction = .014). MLwHF scores at 4 months were somewhat lower (better) with FDI for more anaemic patients (overall Pinteraction = .14; physical Pinteraction = .085; emotional Pinteraction = .043) but were not related to baseline TSAT or ferritin. Blood tests did not predict difference in achieved walking distance for those randomized to FDI compared to control. The absence of anaemia or a TSAT ≥ 20% was associated with lower event rates and little evidence of benefit from FDI. More severe anaemia or TSAT < 20%, especially when ferritin was ≥100 µg/L, was associated with higher event rates and greater absolute reductions in events with FDI, albeit not statistically significant. CONCLUSIONS: This hypothesis-generating analysis suggests that anaemia or TSAT < 20% with ferritin > 100 µg/L might identify patients with heart failure who obtain greater benefit from intravenous iron. This interpretation requires confirmation.

Cost-effectiveness of High-Intensity Interval Training (HIIT) vs Moderate Intensity Steady-State (MISS) Training in UK Cardiac Rehabilitation.

OBJECTIVE: To perform a cost-effectiveness analysis of high-intensity interval training (HIIT) compared with moderate intensity steady-state (MISS) training in people with coronary artery disease (CAD) attending cardiac rehabilitation (CR). DESIGN: Secondary cost-effectiveness analysis of a prospective, assessor-blind, parallel group, multi-center RCT. SETTING: Six outpatient National Health Service cardiac rehabilitation centers in England and Wales, UK. PARTICIPANTS: 382 participants with CAD (N=382). INTERVENTIONS: Participants were randomized to twice-weekly usual care (n=195) or HIIT (n=187) for 8 weeks. Usual care was moderate intensity continuous exercise (60%-80% maximum capacity, MISS), while HIIT consisted of 10 × 1-minute intervals of vigorous exercise (>85% maximum capacity) interspersed with 1-minute periods of recovery. MAIN OUTCOME MEASURES: We conducted a cost-effectiveness analysis of the HIIT or MISS UK trial. Health related quality of life was measured with the EQ-5D-5L to estimate quality-adjusted life years (QALYs). Costs were estimated with health service resource use and intervention delivery costs. Cost-utility analysis measured the incremental cost-effectiveness ratio (ICER). Bootstrapping assessed the probability of HIIT being cost-effective according to the UK National Institute for Health and Care Excellence (NICE) threshold value (£20,000 per QALY). Missing data were imputed. Uncertainty was estimated using probabilistic sensitivity analysis. Assumptions were tested using univariate/1-way sensitivity analysis. RESULTS: 124 (HIIT, n=59; MISS, n=65) participants completed questionnaires at baseline, 8 weeks, and 12 months. Mean combined health care use and delivery cost was £676 per participant for HIIT, and £653 for MISS. QALY changes were 0.003 and -0.013, respectively. For complete cases, the ICER was £1448 per QALY for HIIT compared with MISS. At a willingness-to-pay threshold of £20,000 per QALY, the probability of HIIT being cost-effective was 96% (95% CI, 0.90 to 0.95). CONCLUSION: For people with CAD attending CR, HIIT was cost-effective compared with MISS. These findings are important to policy makers, commissioners, and service providers across the health care sector.

Exploring Changes in Myocyte Structure, Contractility, and Energetics From Mechanical Unloading in Patients With Heart Failure Undergoing Ventricular Assist Device Implantation: A Systematic Review and Meta-Analysis.

AIMS: Recent reports of myocardial recovery after mechanical unloading with left ventricular assist devices (LVADs) have challenged the prevailing notion that end-stage heart failure (HF) is irreversible. To improve our understanding of this phenomenon, we comprehensively analysed the structural, functional, and energetic changes in failing human cardiomyocytes after LVAD implantation. METHODS: Based on a prospectively registered protocol (PROSPERO-CRD42022380214), 30 eligible studies were identified from 940 records with a pooled population of 648 patients predominantly with non-ischaemic cardiomyopathy. RESULTS: LVAD led to a substantial regression in myocyte size similar to that of donor hearts (standardised mean difference, -1.29; p<0.001). The meta-regression analysis revealed that HF duration was a significant modifier on the changes in myocyte size. There were some suggestions of fibrosis reversal (-5.17%; p=0.009); however, this was insignificant after sensitivity analysis. Developed force did not improve in cardiac trabeculae (n=5 studies); however, non-physiological isometric contractions were tested. At the myocyte level (n=4 studies), contractile kinetics improved where the time-to-peak force reduced by 41.7%-50.7% and time to 50% relaxation fell by 47.4%-62.1% (p<0.05). Qualitatively, LVAD enhanced substrate utilisation and mitochondrial function (n=6 studies). Most studies were at a high risk of bias. CONCLUSION: The regression of maladaptive hypertrophy, partial fibrosis reversal, and normalisation in metabolic pathways after LVAD may be a testament to the heart's remarkable plasticity, even in the advanced stages of HF. However, inconsistencies exist in force-generating capabilities. Using more physiological force-length work-loop assays, addressing the high risks of bias and clinical heterogeneity are crucial to better understand the phenomenon of reverse remodelling.

Myocardial Fatigue at a Glance.

Expanding on the modern lexicon of heart failure (HF), the novel mechano-energetic concept of myocardial fatigue describes a transiently energy-depleted myocardium with impaired contractility and relaxation in the face of adverse haemodynamic load. It encompasses established concepts of ventricular-arterial decoupling, deranged cardiac energetics and impaired myocardial efficiency, offering an alternative explanation for functional causes of HF.

The Role of the Vasculature in Heart Failure.

The contribution of the vasculature in the development and progression of heart failure (HF) syndromes is poorly understood and often neglected. Incorporating both arterial and venous systems, the vasculature plays a significant role in the regulation of blood flow throughout the body in meeting its metabolic requirements. A deterioration or imbalance between the cardiac and vascular interaction can precipitate acute decompensated HF in both preserved and reduced ejection fraction phenotypes. This is characterised by the increasingly recognised concept of ventricular-arterial coupling: a well-balanced relationship between ventricular and vascular stiffness, which has major implications in HF. Often, the cause of decompensation is unknown, with international guidelines mainly centred on arrhythmia, infection, acute coronary syndrome and its mechanical complications as common causes of decompensation; the vascular component is often underrecognised. A better understanding of the vascular contribution in cardiovascular failure can improve risk stratification, earlier diagnosis and facilitate earlier optimal treatment. This review focuses on the role of the vasculature by integrating the concepts of ventricular-arterial coupling, arterial stiffness and venous return in a failing heart.

Myocardial Fatigue: a Mechano-energetic Concept in Heart Failure.

PURPOSE OF REVIEW: This review combines existing mechano-energetic principles to provide a refreshing perspective in heart failure (HF) and examine if the phenomenon of myocardial fatigue can be rigorously tested in vitro with current technological advances as a bridge between pre-clinical science and clinical practice. RECENT FINDINGS: As a testament to the changing paradigm of HF pathophysiology, there has been a shift of focus from structural to functional causes, as reflected in its modern universal definition and redefined classification. Bolstered by recent landmark trials of sodium-glucose cotransport-2 inhibitors across the HF spectrum, there is a rekindled interest to revisit the basic physiological tenets of energetic efficiency, metabolic flexibility, and mechanical load on myocardial performance. Indeed, these principles are well established in the study of skeletal muscle fatigue. Since both striated muscles share similar sarcomeric building blocks, is it possible that myocardial fatigue can occur in the face of sustained adverse supra-physiological load as a functional cause of HF? Myocardial fatigue is a mechano-energetic concept that offers a novel functional mechanism in HF. It is supported by current studies on exercise-induced cardiac fatigue and reverse translational science such as from recent landmark trials on sodium glucose co-transporter 2 inhibitors in HF. We propose a novel framework of myocardial fatigue, injury, and damage that aligns with the contemporary notion of HF as a continuous spectrum, helps determine the chance and trajectory of myocardial recovery, and aims to unify the plethora of cellular and molecular mechanisms in HF.

Supervised pulmonary hypertension exercise rehabilitation (SPHERe): study protocol for a multi-centre randomised controlled trial.

BACKGROUND: Supervised cardio-pulmonary rehabilitation may be safe and beneficial for people with pulmonary hypertension (PH) in groups 1 (pulmonary arterial hypertension) and 4 (chronic thromboembolic disease), particularly as a hospital in-patient. It has not been tested in the most common PH groups; 2 (left heart disease), 3 (lung disease), or 5 (other disorders). Further it has not been evaluated in the UK National Health Service (NHS) out-patient setting, or with long-term follow-up. The aim of this randomised controlled trial (RCT) is to test the clinical and cost-effectiveness of a supervised exercise rehabilitation intervention with psychosocial support compared to best practice usual care for people with PH in the community/outpatient setting. METHODS: This multi-centre, pragmatic, two-arm RCT with embedded process evaluation aims to recruit 352 clinically stable adults with PH (groups 1-5) and WHO functional class II-IV. Participants will be randomised to either the Supervised Pulmonary Hypertension Exercise Rehabilitation (SPHERe) intervention or control. The SPHERe intervention consists of 1) individual assessment and familiarisation sessions; 2) 8-week, twice-weekly, supervised out-patient exercise training; 3) psychosocial/motivational support and education; 4) guided home exercise plan. The control intervention consists of best practice usual care with a single one-to-one practitioner appointment, and general advice on physical activity. Outcomes will be measured at baseline, 4 months (post-intervention) and 12 months by researchers blinded to treatment allocation. The primary outcome is the incremental shuttle walk test at 4 months. Secondary outcomes include health-related quality of life (HRQoL), time to clinical worsening and health and social care use. A purposive sample of participants (n = 20 intervention and n = 20 control) and practitioners (n = 20) will be interviewed to explore experiences of the trial, outcomes and interventions. DISCUSSION: The SPHERe study is the first multi-centre clinical RCT to assess the clinical and cost effectiveness of a supervised exercise rehabilitation intervention compared to usual care, delivered in the UK NHS, for people in all PH groups. Results will inform clinicians and commissioners as to whether or not supervised exercise rehabilitation is effective and should be routinely provided for people with PH. TRIAL REGISTRATION: ISRCTN no. 10608766, prospectively registered on 18th March 2019.

Iatrogenic Decompensated Heart Failure.

PURPOSE OF REVIEW: To provide an overview of the potential iatrogenic causes of acute decompensated heart failure (AHF) and an evidence-based management strategy to address this. RECENT FINDINGS: As the heart failure (HF) population continues to age and become burdened with greater comorbidities and polypharmacy, patients become more susceptible to the iatrogenic precipitants of HF. The following clinical scenarios are familiar to clinicians, but the sequelae to AHF are often unanticipated: HF medications withdrawn during an intercurrent illness and not restarted, cardiotoxic therapy prescribed for cancer without timely and regular monitoring of left ventricular function, excessive intravenous fluids administered for sepsis or postoperatively, a blood transfusion volume not adjusted for body weight, iatrogenic anaemia that goes unnoticed or an inappropriate type of pacemaker implanted in a patient with underlying left ventricular systolic dysfunction. Iatrogenic decompensated HF is a phenomenon that is infrequently documented in the literature but increasingly confronted by clinicians of all specialties. It is associated with a high mortality and morbidity rate. By having greater awareness of these triggers, iatrogenic AHF should be one that is prevented rather than managed when it occurs.

Inotropic Agents and Vasopressors in the Treatment of Cardiogenic Shock.

BACKGROUND: Worldwide, cardiogenic shock (CS) is the leading cause of death in patients admitted with an acute myocardial infarction (AMI). CS is characterised by reduced cardiac output secondary to systolic dysfunction which can lead to multi-organ failure. The mainstay of medical treatment in CS are inotropes and vasopressors to improve cardiac output. However, current clinical guidelines do not direct clinicians as to which agents to use and in what combinations. This article aims to review the current evidence on the management of CS with a major focus on the use of inotropes and vasopressors. METHOD: A literature review was conducted analysing published literature from the following databases: PubMed, MedLine, Cochrane Library and Embase, as well as a manual search of articles that were deemed relevant. Relevant articles were identified by using keywords such as "cardiogenic shock". RESULTS: Literature was assessed to review the use of inotropes and vasopressors in CS. Dopamine and adrenaline were associated with increased mortality and arrhythmias. Dobutamine was associated with an improvement in cardiac output, at the determinant of causing arrhythmias. Conversely, noradrenaline was associated with a lower likelihood of arrhythmias and most importantly decreased mortality in CS. Compared to other inotropes, levosimendan appears to have a better safety profile and is associated with decreased mortality in CS, particularly when combined with a vasopressor. Our literature review suggests that treatment combination of the inotrope levosimendan with the vasopressor noradrenaline may be the most effective management option in CS.

Anti-arrhythmic drug therapy in implantable cardioverter-defibrillator recipients.

Implantable cardioverter-defibrillators (ICDs) have revolutionized the primary and secondary prevention of patients with ventricular arrhythmias. However, the adverse effects of appropriate or inappropriate shocks may require the adjunctive use of anti-arrhythmic drugs (AADs). Beta blockers are the cornerstone of pharmacological primary and secondary prevention of ventricular arrhythmias. In addition to their established efficacy at reducing the incidence of ventricular arrhythmias, beta-blockers are safe with few side effects. Amiodarone is superior to beta blockers and sotalol for the prevention of ventricular arrhythmia recurrence. However, long-term amiodarone use is associated with significant side effects that limit its utility. Sotalol and mexiletine are the main alternatives to amiodarone with a better side effect profile though they are less efficacious at preventing ventricular arrhythmia recurrence. Dofetilide, azimilide and ranolazine are emerging as therapeutic options for secondary prevention; more studies are needed to assess efficacy and safety in comparison to currently used agents. Beta blockers and amiodarone are the mainstay of therapy in patients experiencing electrical storm; their use reduces the frequency of ventricular arrhythmias and ICD intervention as well as affording time until catheter ablation can be considered.

Inpatient Monitoring of Decompensated Heart Failure: What Is Needed?

PURPOSE OF REVIEW: Acute decompensated heart failure is a serious and common condition where close monitoring of symptoms, vital signs, haemodynamic and other markers are needed after the patient is admitted to hospital as the in-hospital outcome is poor. This review focuses on advances in the assessment and monitoring of these patients. RECENT FINDINGS: The adoption of the CHAMP acronym to identify precipitating factors and of the classification using wet-warm, wet-cold, dry-warm and dry-cold categories is an improvement regarding assessment. Although the outcome of acute decompensated heart failure has remained poor with no new treatments found for a number of years, a structured approach to assessment and monitoring is now available.

Reduced Cardiovascular Reserve in Chronic Kidney Failure: A Matched Cohort Study.

BACKGROUND: Patients with chronic kidney failure (CKF) experience impaired functional cardiovascular reserve with reduced oxygen consumption at peak exercise (VO(2peak)). No studies have examined whether this is related to impaired cardiovascular compliance as a consequence of loss of adaptive structural alterations, resulting from chronic uremia or hypertension. STUDY DESIGN: Prospective matched-cohort study. SETTING & PARTICIPANTS: We assessed CKF in parallel with patients with essential hypertension but without cardiovascular disease. Patients with CKF were either scheduled for kidney transplantation or transplant waitlisted. 80 patients with CKF and 80 with essential hypertension matched in age, sex, and body mass index were evaluated. 61 patients with CKF (76.3%) were dialysis dependent. PREDICTOR: CKF versus essential hypertension without cardiovascular disease. MEASUREMENTS & OUTCOMES: VO(2peak) was measured during maximal exercise testing. 2-dimensional echocardiography and arterial applanation tonometry were performed prior to exercise testing. To evaluate for the difference in VO(2peak) between study groups, statistically significant predictors of VO(2peak) in multiple regression models were additionally assessed by fitting models comprising the interaction term of patient group with the predictor variable of interest. RESULTS: VO(2peak) was significantly lower in patients with CKF than those with essential hypertension (18.8 vs 24.5 mL/min·kg; P<0.001). Independent predictors of VO(2peak) for CKF included left ventricular (LV) filling pressure (E/mean e'; unstandardized regression coefficient: change in VO(2peak) [in mL/min·kg] per 1-unit change of variable = -5.1) and pulse wave velocity (-4.0); in essential hypertension, these were LV mass index (0.2), LV end-diastolic volume index (0.4), peak heart rate (0.2), and pulse wave velocity (-8.8). The interaction effect of VO(2peak) between patient groups with LV mass index (P<0.001), LV end-diastolic volume index (P<0.001), and peak heart rate (P<0.01) were significantly stronger in the hypertension group, whereby higher values led to greater VO(2peak). LIMITATIONS: Skeletal muscle strength was not assessed. CONCLUSION: This study suggests that maladaptive LV changes, as well as blunted chronotropic response, are important mechanistic factors resulting in reduced cardiovascular reserve in patients with CKF, beyond predominantly vascular changes associated with hypertension.

Functional cardiovascular reserve predicts survival pre-kidney and post-kidney transplantation.

Exercise intolerance is an important comorbidity in patients with CKD. Anaerobic threshold (AT) determines the upper limits of aerobic exercise and is a measure of cardiovascular reserve. This study investigated the prognostic capacity of AT on survival in patients with advanced CKD and the effect of kidney transplantation on survival in those with reduced cardiovascular reserve. Using cardiopulmonary exercise testing, cardiovascular reserve was evaluated in 240 patients who were waitlisted for kidney transplantation between 2008 and 2010, and patients were followed for ≤5 years. Survival time was the primary endpoint. Cumulative survival for the entire cohort was 72.6% (24 deaths), with cardiovascular events being the most common cause of death (54.2%). According to Kaplan-Meier estimates, patients with AT <40% of predicted peak VO2 had a significantly reduced 5-year cumulative overall survival rate compared with those with AT ≥40% (P<0.001). Regarding the cohort with AT <40%, patients who underwent kidney transplantation (6 deaths) had significantly better survival compared with nontransplanted patients (17 deaths) (hazard ratio, 4.48; 95% confidence interval, 1.78 to 11.38; P=0.002). Survival did not differ significantly among patients with AT ≥40%, with one death in the nontransplanted group and no deaths in the transplanted group. In summary, this is the first prospective study to demonstrate a significant association of AT, as the objective index of cardiovascular reserve, with survival in patients with advanced CKD. High-risk patients with reduced cardiovascular reserve had a better survival rate after receiving a kidney transplant.

Inter- and intra-observer reliability and agreement of O2Pulse inflection during cardiopulmonary exercise testing: A comparison of subjective and novel objective methodology.

Cardiopulmonary exercise testing (CPET) is the 'gold standard' method for evaluating functional capacity, with oxygen pulse (O2Pulse) inflections serving as a potential indicator of myocardial ischaemia. However, the reliability and agreement of identifying these inflections have not been thoroughly investigated. This study aimed to assess the inter- and intra-observer reliability and agreement of a subjective quantification method for identifying O2Pulse inflections during CPET, and to propose a more robust and objective novel algorithm as an alternative methodology. A retrospective analysis was conducted using baseline data from the HIIT or MISS UK trial. The O2Pulse curves were visually inspected by two independent examiners, and compared against an objective algorithm. Fleiss' Kappa was used to determine the reliability of agreement between the three groups of observations. The results showed almost perfect agreement between the algorithm and both examiners, with a Fleiss' Kappa statistic of 0.89. The algorithm also demonstrated excellent inter-rater reliability (ICC) when compared to both examiners (0.92-0.98). However, a significant level (P ≤0.05) of systematic bias was observed in Bland-Altman analysis for comparisons involving the novice examiner. In conclusion, this study provides evidence for the reliability of both subjective and novel objective methods for identifying inflections in O2Pulse during CPET. These findings suggest that further research into the clinical significance of O2Pulse inflections is warranted, and that the adoption of a novel objective means of quantification may be preferable to ensure equality of outcome for patients.

Profiling the Biomechanical Responses to Workload on the Human Myocyte to Explore the Concept of Myocardial Fatigue and Reversibility: Rationale and Design of the POWER Heart Failure Study.

It remains unclear why some patients develop heart failure without evidence of structural damage. One theory relates to impaired myocardial energetics and ventricular-arterial decoupling as the heart works against adverse mechanical load. In this original study, we propose the novel concept of myocardial fatigue to capture this phenomenon and aim to investigate this using human cardiomyocytes subjected to a modern work-loop contractility model that closely mimics in vivo cardiac cycles. This proof-of-concept study (NCT04899635) will use human myocardial tissue samples from patients undergoing cardiac surgery to develop a reproducible protocol to isolate robust calcium-tolerant cardiomyocytes. Thereafter, work-loop contractility experiments will be performed over a range of preload, afterload and cycle frequency as a function of time to elicit any reversible reduction in contractile performance (i.e. fatigue). This will provide novel insight into mechanisms behind heart failure and myocardial recovery and serve as a valuable research platform in translational cardiovascular research.

Initial experience of temperature-controlled irrigated radiofrequency ablation for ischaemic cardiomyopathy ventricular tachycardia ablation.

BACKGROUND: The DiamondTemp ablation (DTA) catheter system delivers high power, open-irrigated, temperature-controlled radiofrequency (RF) ablation. This novel ablation system has not been previously used for ventricular tachycardia (VT) ablation. OBJECTIVE: Feasibility of using the DTA catheter system for VT ablation in ischaemic cardiomyopathy (ICM) patients. METHOD: Ten ICM patients with optimal anti-arrhythmic drug therapy and implantable cardiac defibrillators (ICD) were recruited. VT inducibility testing was performed at the end of the procedure. ICD data for device detected VT episodes and device treated VT episodes were collected for 6-months pre- and post-ablation. RESULTS: Substrate analysis demonstrated reductions in the borderzone area of 4.4 cm2 (p = 0.026) and late potential area of 3.5 cm2 (p = 0.0449) post-ablation, with reductions in the mean bipolar and unipolar voltages of the ablation target areas (0.14 mV (p = 0.0007); 0.59 mV (p = 0.0072) respectively). Complete procedural success was achieved in 9 procedures. Post-ablation VT inducibility testing was not performed in 1 procedure due to a steam pop complication resulting in pericardial tamponade requiring drainage. Mean follow-up of 214 ± 33 days revealed an 88% reduction in total VT episodes (n = 266 median 16 [IQR 3-57] to n = 33 median 0; p = 0.0164) and 77% reduction in ICD therapies (n = 128 median 5 [IQR 2-15] to n = 30 median 0; p = 0.0181). CONCLUSION: The DTA system resulted in adequate lesion characteristics with effective substrate modification, acute procedural success and improved outcomes at intermediate-term follow-up. Randomised controlled trials are required to compare the performance of the DTA system against conventional ablation catheters.

Validity and reliability of short-term heart-rate variability from disposable electrocardiography leads.

Background and Aims: Single-use electrocardiography (ECG) leads have been developed to reduce healthcare-associated infection. This study compared the validity and reliability of short-term heart rate variability (HRV) obtained from single-use disposable ECG leads. Methods: Thirty healthy subjects (33 ± 10 years; 9 females) underwent 5-min resting HRV assessments using disposable (single use) ECG cable and wire system (Kendall DL™ Cardinal Health) and a standard, reusable ECG leads (CardioExpress, Spacelabs Healthcare). Results: Intraclass correlation coefficient (ICC) with 95% confidence interval (CI) between disposable and reusable ECG leads was for the time domain [R-R interval (ms); 0.99 (0.91, 1.00)], the root mean square of successive normal R-R interval differences (RMSSD) (ms); 0.91 (0.76, 0.96), the SD of normal-to-normal R-R intervals (SDNN) (ms); 0.91 (0.68, 0.97) and frequency domain [low-frequency (LF) normalized units (nu); 0.90 (0.79, 0.95), high frequency (HF) nu; 0.91 (0.80, 0.96), LF power (ms2); 0.89 (0.62, 0.96), HF power (ms2); 0.90 (0.72, 0.96)] variables. The mean difference and upper and lower limits of agreement between disposable and reusable leads for time- and frequency-domain variables were acceptable. Analysis of repeated measures using disposable leads demonstrated excellent reproducibility (ICC 95% CI) for R-R interval (ms); 0.93 (0.85, 0.97), RMSSD (ms); 0.93 (0.85, 0.97), SDNN (ms); 0.88 (0.75, 0.95), LF power (ms2); 0.87 (0.72, 0.94), and HF power (ms2); 0.88 (0.73, 0.94) with coefficient of variation ranging from 2.2% to 5% (p > 0.37 for all variables). Conclusion: Single-use Kendall DL™ ECG leads demonstrate a valid and reproducible tool for the assessment of HRV.

Rising arterial stiffness with accumulating comorbidities associates with heart failure with preserved ejection fraction.

AIMS: Comorbidities play a significant role towards the pathophysiology of heart failure with preserved ejection fraction (HFpEF), characterized by abnormal macrovascular function and altered ventricular-vascular coupling. However, our understanding of the role of comorbidities and arterial stiffness in HFpEF remains incomplete. We hypothesized that HFpEF is preceded by a cumulative rise in arterial stiffness as cardiovascular comorbidities accumulate, beyond that associated with ageing. METHODS AND RESULTS: Arterial stiffness was assessed using pulse wave velocity (PWV) in five groups: Group A, healthy volunteers (n = 21); Group B, patients with hypertension (n = 21); Group C, hypertension and diabetes mellitus (n = 20); Group D, HFpEF (n = 21); and Group E, HF with reduced ejection fraction (HFrEF) (n = 11). All patients were aged 70 and above. Mean PWV increased from Groups A to D (PWV 10.2, 12.2, 13.0, and 13.7 m/s, respectively) as vascular comorbidities accumulated independent of age, renal function, haemoglobin, obesity (body mass index), smoking status, and hypercholesterolaemia. HFpEF exhibited the highest PWV and HFrEF displayed near-normal levels (13.7 vs. 10 m/s, P = 0.003). PWV was inversely related to peak oxygen consumption (r = -0.304, P = 0.03) and positively correlated with left ventricular filling pressures (E/e') on echocardiography (r = -0.307, P = 0.014). CONCLUSIONS: This study adds further support to the concept of HFpEF as a disease of the vasculature, underlined by an increasing arterial stiffness that is driven by vascular ageing and accumulating vascular comorbidities, for example, hypertension and diabetes. Reflecting a pulsatile arterial afterload associated with diastolic dysfunction and exercise capacity, PWV may provide a clinically relevant tool to identify at-risk intermediate phenotypes (e.g. pre-HFpEF) before overt HFpEF occurs.

Cardiovascular implications and physical activity in middle-aged and older adults with a history of COVID-19 (CV COVID): a protocol for a randomised controlled trial.

BACKGROUND: The clinical manifestation of COVID-19 is associated with infection and inflammation of the lungs, but there is evidence to suggest that COVID-19 may also affect the structure and function of the cardiovascular system. At present, it is not fully understood to what extent COVID-19 impacts cardiovascular function in the short- and long-term following infection. The aim of the present study is twofold: (i) to define the effect of COVID-19 on cardiovascular function (i.e. arterial stiffness, cardiac systolic and diastolic function) in otherwise healthy individuals and (ii) to evaluate the effect of a home-based physical activity intervention on cardiovascular function in people with a history of COVID-19. METHODS: This prospective, single-centre, observational study will recruit 120 COVID-19-vaccinated adult participants aged between 50 and 85 years, i.e. 80 with a history of COVID-19 and 40 healthy controls without a history of COVID-19. All participants will undergo baseline assessments including 12-lead electrocardiography, heart rate variability, arterial stiffness, rest and stress echocardiography with speckle tracking imaging, spirometry, maximal cardiopulmonary exercise testing, 7-day physical activity and sleep measures and quality of life questionnaires. Blood samples will be collected to assess the microRNA expression profiles, cardiac and inflammatory biomarkers, i.e. cardiac troponin T; N-terminal pro B-type natriuretic peptide; tumour necrosis factor alpha; interleukins 1, 6 and 10; C-reactive protein; D-dimer; and vascular endothelial growth factors. Following baseline assessments, COVID-19 participants will be randomised 1:1 into a 12-week home-based physical activity intervention aiming to increase their daily number of steps by 2000 from baseline. The primary outcome is change in left ventricular global longitudinal strain. Secondary outcomes are arterial stiffness, systolic and diastolic function of the heart, functional capacity, lung function, sleep measures, quality of life and well-being (depression, anxiety, stress and sleep efficiency). DISCUSSION: The study will provide insights into the cardiovascular implications of COVID-19 and their malleability with a home-based physical activity intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT05492552. Registered on 7 April 2022.