Cardiorespiratory Fitness and Risk of Cardiovascular Events and Mortality in Middle Age Patients without Known Cardiovascular Disease

Background: Low cardiorespiratory fitness is an established risk predictor for chronic non-communicable diseases. We aimed to investigate the prognostic significance of fitness level on the risk of major adverse cardiac events (MACE, the composite of myocardial infarction, stroke, or all-cause death), in a contemporary cohort of middle-aged subjects without cardiovascular disease. Methods: Retrospective analysis of patients aged 40–60 years without a history of cardiovascular disease. Degree of fitness was determined according to a graded, maximal treadmill exercise stress testing (EST) time achieved, classified into age- and sex-specific quintiles (Q), and categorized as low (Q1), moderate (Q2–Q4) or high (Q5) fitness groups. A multivariable Cox proportional hazard regression model was used to assess the association of fitness level with the risk of MACE. Results: A total of 6836 patients were included, of which 44.5% were women, and the mean age was 52 years. Overall, 289 MACE events occurred during a median follow-up of 7 years. Level of fitness was inversely associated with the presence of cardiovascular risk factors. The multivariable adjusted hazard ratio (95% confidence interval) for MACE was 1.65 (1.12–2.44) and 2.17 (1.40–3.38) in those at moderate and low fitness levels, compared to the high-fitness group (reference), respectively. For each decrease of one metabolic equivalent (MET) unit achieved at peak exercise, the relative risk for MACE increased by 18%. The association between low fitness and MACE was not modified by other risk factors (P-for-interaction non-significant). Conclusions: Low fitness level, as captured by a maximal treadmill EST, is an independent risk predictor for MACE among middle-age individuals without known cardiovascular disease. The association of low fitness with high burden of cardiometabolic risk factors highlight the importance of lifestyle intervention in this patient population

Heart Failure Therapies following Acute Coronary Syndromes with Reduced Ejection Fraction: Data from the ACSIS Survey

Background: Guideline-directed medical therapies for heart failure (HF) may benefit patients with reduced left ventricular ejection fraction (LVEF) following acute coronary syndromes (ACS). Few real-world data are available regarding the early implementation of HF therapies in patients with ACS and reduced LVEF. Methods: Data collected from the 2021 nationwide, prospective ACS Israeli Survey (ACSIS). Drug classes included: (a) angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB) or angiotensin receptor-neprilysin inhibitors (ARNI); (b) beta-blockers; (c) mineralocorticoid receptor antagonist (MRA) and (d) sodium-glucose cotransporter-2 inhibitors (SGLT2I). The utilization of HF therapies at discharge or 90 days following ACS was analyzed in relation to LVEF [reduced ≤40% (n = 406) or mildly-reduced 41–49% (n = 255)] and short-term adverse outcomes. Results: History of HF, anterior wall myocardial infarction and Killip class II-IV (32% vs. 14% p p = 0.084. No association was observed between the number of HF drug classes or the use of ARNI and/or SGLT2I with adverse clinical outcomes. Conclusions: In current clinical practice, the majority of patients with reduced and mildly-reduced LVEF are treated by ACEI/ARB and beta-blockers early following ACS, whereas MRA is underutilized and the adoption of SGLT2I and ARNI is low. A greater number of therapeutic classes was not associated with reduced short-term rehospitalizations or mortality

Involvement of Cytokines in the Pathogenesis of Salt and Water Imbalance in Congestive Heart Failure

Congestive heart failure (CHF) has become a major medical problem in the western world with high morbidity and mortality rates. CHF adversely affects several systems, mainly the kidneys and the lungs. While the involvement of the renin–angiotensin–aldosterone system and the sympathetic nervous system in the progression of cardiovascular, pulmonary, and renal dysfunction in experimental and clinical CHF is well established, the importance of pro-inflammatory mediators in the pathogenesis of this clinical setting is still evolving. In this context, CHF is associated with overexpression of pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-1, and IL-6, which are activated in response to environmental injury. This family of cytokines has been implicated in the deterioration of CHF, where it plays an important role in initiating and integrating homeostatic responses both at the myocardium and circulatory levels. We and others showed that angiotensin II decreased the ability of the lungs to clear edema and enhanced the fibrosis process via phosphorylation of the mitogen-activated protein kinases p38 and p42/44, which are generally involved in cellular responses to pro-inflammatory cytokines. Literature data also indicate the involvement of these effectors in modulating ion channel activity. It has been reported that in heart failure due to mitral stenosis; there were varying degrees of vascular and other associated parenchymal changes such as edema and fibrosis. In this review, we will discuss the effects of cytokines and other inflammatory mediators on the kidneys and the lungs in heart failure; especially their role in renal and alveolar ion channels activity and fluid balance

Psychophysic-psychological dichotomy in very early acute mTBI pain: a prospective study

To characterize the pain-related somatosensory and psychological presentation of very early acute patients with a mild traumatic brain injury (mTBI).Patients with an mTBI participated in a prospective observational study undergoing clinical, psychophysic, and psychological assessment within 72 hours after the accident. Healthy controls underwent similar protocol.One hundred acute patients with an mTBI (age 36 ± 12.5 [SD] years, range 19-67 years, 42 women) and 80 healthy controls (age 43 ± 14.3 years, range 24-74 years, 40 women) participated. Patients with an mTBI demonstrated a pronociceptive psychophysic response in most tests such as less efficient pressure-pain threshold-conditioned pain modulation (0.19 ±0.19±.09 vs. 0.91±.10 kg, < 0.001) and lower temperature needed to elicit a Pain50 response (44.72 ± 0.26°C vs 46.41 ± 0.30°C, < 0.001). Their psychophysic findings correlated with clinical pain measures, e.g., Pain50 temperature and mean head ( = -0.21, = 0.045) and neck ( = -0.26, = 0.011) pain. The pain-catastrophizing magnification subscale was the only psychological variable to show a difference from the controls, while no significant correlations were found between any psychological measures and the clinical or psychophysic pain measures.There appears to be a dichotomy between somatosensory and psychological findings in the very early acute post-mTBI stage; while the first is altered and is associated with the clinical picture, the second is unchanged. In the context of the ongoing debate on the pathophysiologic nature of the post-mTBI syndrome, our findings support its "physical" basis, free of mental influence, at least in the short time window after the injury

Sequencing and titrating approach of therapy in heart failure with reduced ejection fraction following the 2021 European Society of Cardiology guidelines: an international cardiology survey

AIMS: In symptomatic patients with heart failure and reduced ejection fraction (HFrEF), recent international guidelines recommend initiating four major therapeutic classes rather than sequential initiation. It remains unclear how this change in guidelines is perceived by practicing cardiologists versus heart failure (HF) specialists. METHODS AND RESULTS: An independent academic web-based survey was designed by a group of HF specialists and posted by email and through various social networks to a broad community of cardiologists worldwide 1 year after the publication of the latest European HF guidelines. Overall, 615 cardiologists (38 [32-47] years old, 63% male) completed the survey, of which 58% were working in a university hospital and 26% were HF specialists. The threshold to define HFrEF was ≤40% for 61% of the physicians. Preferred drug prescription for the sequential approach was angiotensin-converting enzyme inhibitors or angiotensin receptor-neprilysin inhibitors first (74%), beta-blockers second (55%), mineralocorticoid receptor antagonists third (52%), and sodium-glucose cotransporter 2 inhibitors (53%) fourth. Eighty-four percent of participants felt that starting all four classes was feasible within the initial hospitalization, and 58% felt that titration is less important than introducing a new class. Age, status in training, and specialization in HF field were the principal characteristics that significantly impacted the answers. CONCLUSION: In a broad international cardiology community, the 'historical approach' to HFrEF therapies remains the preferred sequencing approach. However, accelerated introduction and uptitration are also major treatment goals. Strategy trials in treatment guidance are needed to further change practices

Sequencing and Titrating Approach of Therapy in Heart Failure with Reduced Ejection Fraction Following the 2021 ESC guidelines: an International Cardiology Survey

International audienceThe latest European guidelines for heart failure with reduced ejection fraction (HFrEF) patients recommend initiating four major therapeutic classes rather than the sequential initiation from the previous guidelines. Without any evidence from randomized controlled trials, the perception and the practical approach to these guidelines by practicing cardiologists remain unclear. We found that left ventricular ejection fraction (LVEF) ≤40% remains the most frequent threshold to define HFrEF and the ‘historical’ approach to HFrEF drug titration remains the most popular sequencing approach. However, most participants felt that starting all four classes was feasible within the initial hospitalization and that titration is less important than introducing a new class. This is the first and largest survey providing real-world data on HFrEF drug introduction and titration after the latest European heart failure guidelines. Even if the ‘historical’ sequencing approach remains dominant, starting all four classes in a short-time period was perceived as feasible. Strategy trials in treatment guidance are now needed to demonstrate the safety and define the best treatment implementation approac