Blood pressure response to graded bicycle exercise in males and females across the age and fitness spectrum.

AIM: Blood pressure (BP) responses to exercise are frequently measured, with the concern that greater increases are a marker of disease. We sought to characterize the normal exercise BP response in healthy adults and its relationships with age, sex, and fitness. METHODS: 589 participants (median age 46 [IQR 24-56] years, 81% male) underwent cardiopulmonary exercise testing with repeated, automated BP measures. An exaggerated maximal systolic BP (SBPmax) was defined from current guidelines as ≥210 mmHg in males and ≥190 mmHg in females. Individual linear regression analyses defined the relationship between BP and workload (SBP/W-slope and DBP/W-slope). Participants with or without an exaggerated SBPmax and above or below median SBP/W-slope were compared. RESULTS: An exaggerated SBPmax was found in 51% of males and 64% of females and was more prevalent in endurance-trained athletes (males 58%, females 72%, p<0.001). The mean SBP/W-slope was lower in males (0.24±0.10 mmHg/W) than females (0.27±0.12 mmHg/W), p=0.031. In both sexes, peak oxygen uptake (VO2peak) was inversely correlated with SBP/W-slope (p<0.01). Those with an exaggerated SBPmax and below-median SBP/W-slope were 10 years younger and had a 20% higher VO2peak, on average (p<0.001). A non-exaggerated SBPmax and above-median SBP/W-slope was observed in older individuals with the lowest VO2peak. CONCLUSION: In a large cohort of healthy individuals, an exaggerated SBPmax was common and associated with higher fitness. In contrast, higher SBP indexed to workload was associated with older age, lower fitness, and female sex. Thus, sex, age and fitness should be considered when evaluating BP response to exercise.

We evaluated the predictors of blood pressure responses to exercise in 589 healthy individuals. We showed that there is a strong, positive relationship between the increase in systolic blood pressure during exercise with cardiorespiratory fitness and exercise workload.During intensive exercise, high maximal systolic blood pressures are more prevalent in young fit individuals than older, less fit individuals. Systolic blood pressure measures are higher in females than males when indexed to workload.Previous diagnostic cut-offs for peak exercise blood pressure are frequently exceeded in healthy individuals and are likely to have poor disease specificity. Workload-indexed exercise blood pressure is therefore a more informative metric than peak exercise blood pressure.

Characterizing the influence of cardiorespiratory fitness on left atrial size and function in the general population.

Increased left atrial (LA) size and reduced LA function have been associated with heart failure and atrial fibrillation (AF) in at-risk populations. However, atrial remodeling has also been associated with exercise training and the relationship between fitness, LA size, and function has not been defined across the fitness spectrum. In a cross-sectional study of 559 ostensibly healthy participants, comprising 304 males (mean age, 46 ± 20 yr) and 255 females (mean age, 47 ± 15 yr), we sought to define the relationship between cardiorespiratory fitness (CRF), LA size, and function. We also aimed to interrogate sex differences in atrial factors influencing CRF. Echocardiographic measures included biplane measures of LA volumes indexed to body surface area (LAVi) and atrial deformation using two-dimensional speckle tracking. CRF was measured as peak oxygen consumption (V̇o2peak) during cardiopulmonary exercise testing (CPET). Using multivariable regression, age, sex, weight, and LAVi (P < 0.001 for all) predicted V̇o2peak (P < 0.001, R2 = 0.66 for combined model). After accounting for these variables, heart rate reserve added strength to the model (P < 0.001, R2 = 0.74) but LA strain parameters did not predict V̇o2peak. These findings add important nuance to the perception that LA size is a marker of cardiac pathology. LA size should be considered in the context of fitness, and it is likely that the adverse prognostic associations of increased LA size may be confined to those with LA enlargement and low fitness.NEW & NOTEWORTHY Left atrial (LA) structure better predicts cardiorespiratory fitness (CRF) than LA function. LA function adds little statistical value to predictive models of peak oxygen uptake (V̇o2peak) in healthy individuals, suggesting limited discriminatory for CRF once LA size is factored. In the wider population of ostensibly healthy individuals, the association between increased LA volume and higher CRF provides an important counter to the association between atrial enlargement and heart failure symptoms in those with cardiac pathology.

Gene Therapy in Cardiology: Is a Cure for Hypertrophic Cardiomyopathy on the Horizon?

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy worldwide, affecting approximately 1 in 500 individuals. Current therapeutic interventions include lifestyle optimisation, medications, septal reduction therapies, and, rarely, cardiac transplantation. Advances in our understanding of disease-causing genetic variants in HCM and their associated molecular mechanisms have led to the potential for targeted therapeutics and implementation of precision and personalised medicine. Results from preclinical research are promising and raise the question of whether cure of some subtypes of HCM may be possible in the future. This review provides an overview of current genetic therapy platforms, including 1) genome editing, 2) gene replacement, 3) allelic-specific silencing, and 4) signalling pathway modulation. The current applicability of each of these platforms within the paradigm of HCM is examined, with updates on current and emerging trials in each domain. Barriers and limitations within the current landscape are also highlighted. Despite recent advances, translation of genetic therapy for HCM to clinical practice is still in early development. In realising the promises of genetic HCM therapies, ethical and equitable access to safe gene therapy must be prioritised.

Understanding Exercise Capacity: From Elite Athlete to HFpEF.

Exercise capacity is a spectrum that reflects an individual's functional capacity and the dynamic nature of cardiac remodelling along with respiratory and skeletal muscle systems. The relationship of increasing physical activity, increased cardiac mass and volumes, and improved cardiorespiratory fitness (CRF) is well established in the endurance athlete. However, less emphasis has been placed on the other end of the spectrum, which includes individuals with a more sedentary lifestyle and small hearts who are at increased risk of functional disability and poor clinical outcomes. Reduced CRF is an independent predictor of all-cause mortality and cardiovascular events determined by multiple inter-related exogenous and endogenous factors. In this review, we explore the relationship of physical activity, cardiac remodelling, and CRF across the exercise spectrum, emphasising the critical role of cardiac size in determining exercise capacity. In contrast to the large compliant left ventricle of the endurance athlete, an individual with a lifetime of physical inactivity is likely to have a small, stiff heart with reduced cardiac reserve. We propose that this might contribute to the development of heart failure with preserved ejection fraction in certain individuals, and is key to understanding the link between low CRF and increased risk of heart failure.

A systematic review of global autopsy rates in all-cause mortality and young sudden death.

Autopsy is the gold standard method for determining cause of death. Young sudden death (SD) is a prototype condition in which autopsy is universally recommended. The aim of this review was to quantify real-world global rates of autopsy in either all-cause death or young SD. A systematic review was conducted. Rates of autopsy in all-cause death and in young SD were determined in each country using scientific and commercial search engines. In total, 59 of 195 countries (30.3%) reported autopsy rates in all-cause death, with rates varying from 0.01%-83.9%. Almost all of these figures derived from academic publications rather than governmental statistics. Only 16 of 195 countries (8.2%) reported autopsy rates in the context of young SD, with reported rates ranging from 5%-100%. The definition of "young" was heterogeneous. No governmental statistics reported autopsy rates in young SD. Risks of bias included inability to verify reported figures, heterogeneity in reporting of clinical vs medicolegal autopsies, and the small number of studies identified overall, resulting in the consistent exclusion of low- and middle-income countries. In conclusion, most countries globally do not report autopsy rates in either all-cause death (69.7%) or in SD (92.8%). Without transparent reporting of autopsy rates, global burdens of disease and rates of sudden cardiac death cannot be reliably calculated.

Telehealth in Australian cardiology: insight into factors predicting the use of telephone versus video during the COVID-19 pandemic.

BACKGROUND: The use of telehealth has increased dramatically in Australia in 2020 as a pragmatic response to the COVID-19 pandemic; however, differences between telehealth modalities have not been established. AIM: To identify characteristics contributing to choosing telephone (TP) versus video consultation (VC) and assess patient outcomes between telehealth modalities. METHODS: We conducted an observational study of cardiology outpatients at a tertiary hospital with appointments from 17 March 2020 to 12 August 2020. Demographic variables and appointment modality were compared between each group. Outcomes assessed were mortality, emergency department (ED) presentations and cross over between appointment modalities. RESULTS: There were 1754 telemedicine encounters with 1188 patients seen by TP and 327 patients by VC. Consulting volume increased from previous years. Cardiac mortality was low (0.3%). There were no differences in mortality or ED presentations between telehealth modalities. Patients choosing TP over VC were older (P < 0.001), more likely to be female (P = 0.005), non-English-speaking (P = 0.041), living in metropolitan Melbourne (P < 0.0001), undertaking a first appointment (P = 0.002) and seeing particular cardiologists (P < 0.001). VC patients were more likely to have early review (P = 0.015), and this was likely to be TP (P < 0.0001). TP patients were more likely to follow up in person (P < 0.0001). CONCLUSION: During COVID-19, we increased consultation volumes without adverse patient outcomes. We identified factors influencing the choice of telemedicine modality which did not translate into differences in mortality or ED presentations. Telemedicine is a growing platform with an important role of facilitating access to healthcare for diverse patient groups.