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 remodeling 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 remodeling , and CRF across the exercise spectrum, emphasizing 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

Continuous infusion of time-dependent antibiotics: lung pharmacokinetics and pharmacodynamics

Lung infections continue to represent a significant burden to the healthcare system and improved antibiotic therapy may serve as a means to improve patient outcomes. Time-dependent antibiotics such as [beta]-lactams and glycopeptides are commonly used as therapy for lung infections, and the emerging data suggest that administration by continuous infusion may result in improved patient outcomes. The aim of this review is to identify and analyze the published literature on lung penetration of time-dependent antibiotics administered by continuous infusion. Although only 16 relevant articles were identified during this structured review, data suggest that continuous infusion may have an important role in therapy for various lung infections. In acute lung injury, such as pneumonia, where local inflammation causes tight junctions between alveolar membrane epithelial cells to open, antibiotic penetration is significant. Continuous infusion of time-dependent antibiotics in these patients results in higher trough concentrations than bolus administration that optimizes the pharmacodynamic properties of these antibiotics. In chronic lung injuries, as evidenced in cystic fibrosis and chronic bronchitis, fibrotic scarring and the presence of thick mucus leads to highly variable but significantly reduced antibiotic penetration. In the presence of such pathology, continuous infusion of these antibiotics seems to normalize variable pharmacokinetic parameters as well as result in higher trough concentrations compared with bolus administration. Continuous infusion of time-dependent antibiotics seems to be a suitable method for optimizing antibiotic concentrations at the site of lung infections and as a result may lead to improved treatment success

Burn resuscitation - hourly urine output vs alternative endpoints: a systematic review

Controversy remains over appropriate endpoints of resuscitation during fluid resuscitation in early burns management. We reviewed the evidence as to whether utilizing alternative endpoints to hourly urine output produces improved outcomes. MEDLINE, CINAHL, EMBASE, Cochrane Library, Web of Science, and full-text clinicians’ health journals at OVID, from 1990 to January 2014, were searched with no language restrictions. The keywords burns AND fluid resuscitation AND monitoring and related synonyms were used. Outcomes of interest included all-cause mortality, organ dysfunction, length of stay (hospital, intensive care), time on mechanical ventilation, and complications such as incidence of pulmonary edema, compartment syndromes, and infection. From 482 screened, eight empirical articles, 11 descriptive studies, and one systematic review met the criteria. Utilization of hemodynamic monitoring compared with hourly urine output as an endpoint to guide resuscitation found an increased survival (risk ratio [RR], 0.58; 95% confidence interval, 0.42–0.85; P < 0.004), with no effect on renal failure (RR, 0.77; 95% confidence interval, 0.39–1.43; P = 0.38). However, inclusion of the randomized controlled trials only found no survival advantage of hemodynamic monitoring over hourly urine output (RR, 0.72; 95% confidence interval, 0.43–1.19; P = 0.19) for mortality. There were conflicting findings between studies for the volume of resuscitation fluid, incidence of sepsis, and length of stay. There is limited evidence of increased benefit with utilization of hemodynamic monitoring, however, all studies lacked assessor blinding. A large multicenter study with a priori–determined subgroup analysis investigating alternative endpoints of resuscitation is warranted

Cardiovascular mortality post burn injury

Background: Burn injury is responsible for both acute and ongoing inflammation, resulting in systematic changes impacting the cardiovascular, hepatobiliary, endocrine, and metabolic systems, but there is minimal investigation into long-term clinical outcomes. This study aimed to investigate mortality due to cardiovascular related long-term postburn injury. Methods: This was a retrospective cohort study linking a burns unit database with mortality outcomes from a Registry of Births, Deaths and Marriages. Data were extracted from the Australian Institute of Health and Welfare and stratified into three age groups: 15 to 44 years, 45 to 64 years, and 65+ years. Mortality rate ratios (MRRs) and 95% confidence interval (CI) were calculated to compare the burns cohort mortality incidence rates with the national mortality incidence rates for each of the three age groups. Logistic regression was used to identify demographic and clinical factors associated with cardiovascular mortality. Results: A total of 4,134 individuals in the database were analyzed according to demographic and clinical variables. The 20-year age-standardized cardiovascular mortality rate for the burns cohort was significantly higher compared with the Australian population (250.6 per 100,000 person-years vs. 207.9 per 100,000 person-years) (MRR, 1.21; 95% CI, 1.001-1.45). Cardiovascular mortality was significantly higher in males aged 15-44 and 45-64 years had a cardiovascular mortality rate significantly higher than the Australian population (MRR = 10.06, 95% CI 3.49-16.63), and (MRR = 2.40, 95% CI 1.42-3.38) respectively. Those who died of cardiovascular disease were more frequently intubated postburn injury (p = 0.01), admitted to intensive care (p < 0.0001), and had preexisting comorbid physical conditions (60.9% vs. 15.0%, p < 0.0001). Conclusion: Survivors from burn injury, especially young males, are at increased long-term risk of death from cardiovascular disease. Increased screening and counseling pertaining to lifestyle factors should be standard management postburn injury. Longitudinal observation of physiological changes, investigation of mechanistic factors, and investigation of interventional strategies should be instituted. Level of Evidence: Prognostic and Epidemiologic; Level IV

Sex disparities in bystander defibrillation for out-of-hospital cardiac arrest

Background: Previous studies have suggested that females experiencing out-of-hospital cardiac arrest (OHCA) receive lower rates of both bystander cardiopulmonary resuscitation (CPR) and defibrillation compared to males. Whether this disparity has improved over time is unknown. Methods: A state-wide OHCA registry in Victoria, Australia collected data over twenty years (2002–2021) regarding rates of bystander interventions in OHCA. Characteristics and outcomes of each OHCA were compared with logistic regression according to sex and time (defined in two-year periods). Results: 32,502 OHCAs were included (69.7% male). Both bystander CPR and defibrillation rates increased for females over time (p < 0.0001). There was no sex disparity in receipt of bystander CPR after adjustment for baseline differences. Females were less likely than males to receive bystander defibrillation, with sex disparity increasing from 2010 onwards (adjOR 0.26 (95%CI 0.09–0.80) in 2020–21 for females compared to males). Conclusion: Initiatives to increase bystander CPR and defibrillation have resulted in higher overall rates of bystander interventions in the last two decades and no significant sex differences in provision of bystander CPR. However, females receive less bystander defibrillation than males, and sex disparity is increasing. Strategies to promote bystander defibrillation in females experiencing OHCA with a shockable rhythm should be a priority

Rheumatic heart disease in Timor-Leste school students: an echocardiography-based prevalence study.

To determine the prevalence of rheumatic heart disease (RHD) in school-aged children and young people in Timor-Leste. Prospective cross-sectional survey. Echocardiography was performed by Australian cardiologists to determine the presence of RHD. Demographic data were also collected. Patients in whom RHD was detected were entered into a register to allow monitoring of adherence to secondary prophylaxis; the first dose of benzathine penicillin G (BPG) was administered on the day of screening. Schools in urban (Dili) and rural (Ermera) Timor-Leste. School students aged 5-20 years. Definite and borderline RHD, as defined by World Heart Federation echocardiographic criteria. 1365 participants were screened; their median age was 11 years (IQR, 9-14 years), and 53% were girls. The estimated prevalence of definite RHD was 18.3 cases per 1000 population (95% CI, 12.3-27.0 per 1000), and of definite or borderline RHD 35.2 per 1000 (95% CI, 26.5-46.4 per 1000). Definite (adjusted odds ratio [aOR], 3.5; 95% CI, 1.3-9.4) and definite or borderline RHD (aOR, 2.7; 95% CI, 1.4-5.2) were more prevalent among girls than boys. Eleven children (0.8%) had congenital heart disease. Of the 25 children in whom definite RHD was identified, 21 (84%) received education and a first dose of BPG on the day of screening; all 25 have since received education about primary care for RHD and have commenced penicillin prophylaxis. The rates of RHD in Timor-Leste are among the highest in the world, and prevalence is higher among girls than boys. Community engagement is essential for ensuring follow-up and the effective delivery of secondary prophylaxis