A human's ability to transfer oxygen from the environment to skeletal muscle and conversely remove carbon dioxide from skeletal muscle back to the environment during physical exertion is a critical representation of heal...A human's ability to transfer oxygen from the environment to skeletal muscle and conversely remove carbon dioxide from skeletal muscle back to the environment during physical exertion is a critical representation of healthy longevity and functional capacity. Cardiorespiratory fitness (CRF) is the accepted construct for the assessment of oxygen consumption (VO) and carbon dioxide production (VCO) - CRF is most accurately quantified through cardiopulmonary exercise testing (CPET) in the clinical setting. All pharmacological interventions, from experimental to approved and on the market, are meant to impact one or more human physiological processes. In this context, the graphical primer on the physiological process of VO and VCO presented herein should facilitate the thought process on how pharmacology interacts with the factors that influence the capacity for physical exertion. Exercise is medicine and CRF is a vital sign and as such, the former should be prescribed to all capable individuals, and the latter should be considered a primary efficacy outcome measure in clinical and research settings. There is an opportunity to synergize and further enhance patient outcomes when pharmacologic and exercise interventions are considered integrated and in combination- a concept recently defined as pharma-cise - the graphical primer is proposed to facilitate application of this concept.
Fernández Ruiz A, Ruiz Ortiz M, Fernández-Avilés Irache C
… +7 more, Rodríguez Almodóvar AM, Delgado Ortega M, Esteban Martínez F, Resúa Collazo A, Heredia Campos G, Pan Álvarez-Ossorio M, Mesa Rubio D
Piserra López Fernández de Heredia A, Ruiz Ortiz M, Torres Llergo J
… +17 more, Carrillo Bailen M, Sánchez de Castro M, Fernández de la Mata M, Díaz Exposito A, Pérez Cabeza AI, Delgado Ortega M, García Fortes M, Fernández Valenzuela I, Chaparro Muñoz M, Rodríguez Fernández A, Rodríguez Almodóvar AM, Alarcón de la Lastra Cubiles I, Esteban Martínez F, Capote Huelva FJ, Sánchez Fernandez JJ, Mesa Rubio D, Working Groups of Atrial Fibrillation and Cardio-Onco-Hematology of the Andalusian Society of Cardiology
BACKGROUND: Diabetic retinopathy, a microvascular complication of diabetes, is a significant marker of systemic vascular damage, which has been linked to increased cardio-renal disease risks. This study investigates the...BACKGROUND: Diabetic retinopathy, a microvascular complication of diabetes, is a significant marker of systemic vascular damage, which has been linked to increased cardio-renal disease risks. This study investigates the impact of diabetic retinopathy on all-cause mortality and adverse cardiovascular and renal outcomes in patients with established heart failure with reduced ejection fraction (HFrEF) using real-world data. METHODS: Using data from January 1, 2012, to December 31, 2021, we conducted a propensity-matched analysis of two cohorts of patients with HFrEF and diabetes without chronic kidney disease (CKD, estimated glomerular filtration rate >60 mL/min/1.73 m²), differentiated by the presence or absence of diabetic retinopathy diagnosis in the TriNetX platform. The primary outcome was all-cause mortality, with secondary outcomes including acute HF, CKD progression, major adverse cardiovascular events, stroke, in-patient hospitalizations, venous thromboembolism (VTE), and peripheral arterial disease (PAD). RESULTS: Following propensity score matching across demographics and clinical variables, each cohort included 15,218 patients. Acute HF was more common in the retinopathy vs non-retinopathy cohort (HR: 1.13, 95 % CI: 1.06-1.20). Results also showed significant increased risks for CKD progression (HR: 1.39, 95 % CI: 1.30-1.50), stroke (HR: 1.18, 95 % CI: 1.08-1.28), as well as PAD (HR: 1.58, 95 % CI: 1.42-1.76) for patients with diabetic retinopathy. CONCLUSION: Diabetic retinopathy is associated with an increased risk of adverse cardio-renal outcomes in patients with established HFrEF.
PURPOSE: Tafamidis was FDA-approved for Transthyretin cardiomyopathy (ATTR-CM) due to its demonstrated reduction in mortality and hospitalizations. METHODS: 976 studies from PubMed and Embase were screened. Seven studies...PURPOSE: Tafamidis was FDA-approved for Transthyretin cardiomyopathy (ATTR-CM) due to its demonstrated reduction in mortality and hospitalizations. METHODS: 976 studies from PubMed and Embase were screened. Seven studies were included that compared tafamidis treatment with no tafamidis for ATTR-CM. The mantel-Haenszel method was used for binary outcomes, and Hedges' g was used for continuous outcomes. RESULTS: Tafamidis was associated with decreased odds of mortality (OR 0.55, 95 % CI 0.42-0.73, I=41 %, p<0.0001) and reduced CHF exacerbations (OR 0.71, 95 % CI 0.51-0.99, I= 0 %, p= 0.04). While, CHF related hospitalizations (OR 0.35, 95 % CI 0.07-1.67, I2= 87 %, p= 0.19), atrial arrhythmias (OR 0.98, 95 % CI 0.67-1.42, I= 0 %, p= 0.9), change in left ventricular ejection fraction (SMD 0.87, 95 % CI -0.37-2.11, I=98 %, p= 0.17), left ventricular end-diastolic diameter from baseline (SMD -0.12, 95 % CI -0.41-0.18, I= 0 %, p= 0.4), interventricular septal thickness from baseline (SMD -0.7, 95 % CI -1.57-0.17, I= 96 %, p= 0.11) were not statistically different for tafamidis compared to no tafamidis for ATTR-CM. CONCLUSION: Tafamidis treatment in ATTR-CM is associated with reduced all-cause mortality and a lower incidence of CHF exacerbations. These observations are consistent with the ATTRACT trial, which supports the efficacy of tafamidis in treating ATTR-CM.
Asymptomatic atherosclerotic cardiovascular disease (ASCVD) is the leading cause of sudden cardiac death (SCD) in athletes over 35 years of age. Despite their high physical fitness, athletes in this age group remain vuln...Asymptomatic atherosclerotic cardiovascular disease (ASCVD) is the leading cause of sudden cardiac death (SCD) in athletes over 35 years of age. Despite their high physical fitness, athletes in this age group remain vulnerable to undetected coronary atherosclerosis, which predisposes them to plaque rupture and acute coronary thrombosis. In contrast, congenital coronary anomalies are the predominant cause of SCD in younger athletes. While SCD accounts for over 90 % of sports-related cardiovascular mortality, identifying at-risk individuals remains challenging due to the silent progression of coronary artery disease (CAD). Current screening methods, such as electrocardiography and stress testing, have limited sensitivity for detecting asymptomatic ASCVD, underscoring the need for advanced imaging modalities like coronary computed tomography angiography (CCTA) in high-risk populations. Risk mitigation requires a multifaceted approach: Tailored pre-participation cardiovascular screening incorporating age-specific risk factors, lifestyle interventions targeting atherosclerosis progression, education for early recognition of cardiac symptoms, and widespread availability of automated external defibrillators (AEDs) during athletic events. Emerging evidence supports integrating biomarkers, for instance, coronary calcium scoring and genetic testing for congenital anomalies, to enhance risk stratification. A comprehensive strategy combining targeted screening, advanced diagnostics, and evidence-based interventions is critical to reducing SCD incidence and improving outcomes in athletes.
Decotto S, Fernandez Villar G, Rossi E
… +9 more, Iroulart JM, Bergier M, Del Castillo S, Perez de Arenaza D, Lillo E, Bluro IM, Falconi ML, Belziti C, Pizarro R
BACKGROUND: The TAPSE/PASP ratio reflects right ventricle-pulmonary artery (RV-PA) coupling and has prognostic value in patients with heart failure, regardless of left ventricular ejection fraction (LVEF). The objective...BACKGROUND: The TAPSE/PASP ratio reflects right ventricle-pulmonary artery (RV-PA) coupling and has prognostic value in patients with heart failure, regardless of left ventricular ejection fraction (LVEF). The objective of this study was to assess the prognostic impact of the TAPSE/PASP ratio in elderly patients hospitalized for acute heart failure with preserved ejection fraction (HFpEF). METHODS: Prospective, observational, and single-center cohort study included patients aged ≥75 years, hospitalized for HFpEF (LVEF >50 %) from September 2019 to December 2023. We excluded patients with significant left-sided valvular disease, advanced renal failure, recent myocardial infarction, and pacemaker users. We defined RV-PA uncoupling as a TAPSE/PASP ratio ≤0.40 using ROC analysis and the Youden index. The primary endpoint was a composite of all-cause mortality and HF rehospitalization at one year. RESULTS: We included a total of 142 patients. The median age was 84 [IQR 78-88] years, and 65 % (n = 92) were female. The mean LVEF was 56 % (±4 %), and 37 % (n = 53) had RV-PA uncoupling. Patients with uncoupling had higher NT-proBNP (5300 [3107-7257] vs. 2740 [1300-5857] pg/dL; p = 0.01) and troponin levels (48 [32-100] vs. 33 [19-61] pg/dL; p = 0.02), along with worse RV function compared to patients without RV-PA uncoupling. The primary endpoint occurred more frequently in patients with RV/PA uncoupling (62 % vs. 33 %; p = 0.001). In the Cox multivariate analysis, RV-PA uncoupling was independently associated with the primary endpoint (HR 2.37; 95 % CI 1.38-4.07; p = 0.02), after adjusting for age and NT-proBNP levels. CONCLUSION: In elderly patients hospitalized for HFpEF, RV-PA uncoupling, defined by a TAPSE/PASP ratio ≤ 0.40 was significantly associated with worse outcomes during one-year follow-up.
BACKGROUND: Heart failure is a syndrome with high morbidity and mortality, influenced by various regional factors. OBJECTIVE: This study aimed to enhance heart failure management by identifying factors that can improve t...BACKGROUND: Heart failure is a syndrome with high morbidity and mortality, influenced by various regional factors. OBJECTIVE: This study aimed to enhance heart failure management by identifying factors that can improve the quality of life and survival of patients in eastern DR Congo. METHODS: Conducted from January 1, 2022, to December 31, 2023, this descriptive analytical study included 156 heart failure patients (mean age 62 ± 15), comprising 80 males and 76 females. Each patient was followed for 12 months. RESULTS: The frequency of heart failure was 17.5 % (156 out of 2732 patients) at the cardiology center. Severity correlated with the use of indigenous anti-poison products (p 0.000) and valvular heart disease (p 0.000). Mortality was notably influenced by indigenous anti-poison product use (41.2 % mortality; p 0.000), duration of diabetes (≤ 1 year 7.4 %; 2-5 years 11.1 %; > 5 years 33.3 %; p 0.014), dilated cardiomyopathy (18.9 % vs. 1.2 % for non-dilated; p 0.000), and valvular heart disease (17.5 % vs. 1.3 %; p 0.003). Mortality rates varied by heart failure phenotype (HFrEF 30.9 %, HFmEF 5.1 %, HFpEF 0.0 %; p 0.000) and severity (NYHA IV 55.6 % vs. NYHA I and II 0.0 %). CONCLUSION: Indigenous anti-poison products and rheumatic valvular heart disease contribute to the worsening and premature death of heart failure patients. Addressing these factors may improve patient survival in this region.
PURPOSE: Malignant hypertension (MHT) is a condition with high morbidity and mortality, necessitating a deeper understanding of its clinical heterogeneity for improved patient management. Aim of our study was to identify...PURPOSE: Malignant hypertension (MHT) is a condition with high morbidity and mortality, necessitating a deeper understanding of its clinical heterogeneity for improved patient management. Aim of our study was to identify/characterize specific phenotypic groups and examine their associations with mortality. METHODS: Data from the West Birmingham MHT Registry were used. We performed two-step cluster analysis to determine distinct groups. Kaplan-Meier curves and Cox proportional hazard models were used to examine the associations of clusters with mortality. RESULTS: 323 patients (mean age 49±13 years; 34 % female) with a median follow-up of 11 (IQR 3-18) years were included. Four clusters were identified; Cluster 1: younger age, intermediate prevalence of cardiovascular risk factors, high prevalence of renal/retinal damage; Cluster 2: older age, female, low prevalence of cardiovascular risk factors, intermediate levels of organ damage; Cluster 3: intermediate age, male, high prevalence of cardiovascular risk factors, high retinal damage; Cluster 4: younger age, male, low prevalence of cardiovascular risk factors, low prevalence of organ damage. In Kaplan Meier curves cluster 4 exhibited the lowest risk, while cluster 3 the highest risk for outcomes (log rank p < 0.001). In Cox regression, all clusters had higher risk of mortality compared to cluster 4; cluster 1 [HR 1.74 (1.07-2.82)], cluster 2 [HR 1.87 (1.20-2.91)], cluster 3 [HR 2.35 (1.54-3.58)]. CONCLUSIONS: Four distinct phenotypic clusters were identified within our registry, having diverse associations with mortality. These clusters offer a framework for more targeted risk stratification and prognostication, with implications for individualized patient care in this high-risk hypertensive population.
Cardiac amyloidosis (CA) is a once underdiagnosed and often fatal condition that has evolved into a disease with expanding diagnostic and therapeutic possibilities. It is characterized by the extracellular deposition of...Cardiac amyloidosis (CA) is a once underdiagnosed and often fatal condition that has evolved into a disease with expanding diagnostic and therapeutic possibilities. It is characterized by the extracellular deposition of misfolded amyloid proteins within the myocardium, leading to structural and functional impairment. Advances in understanding the pathophysiology encompassing the amyloid protein misfolding, aggregation and deposition in cardiac tissue as well as the role of genetic factors have been pivotal in driving progress in diagnosis and management. The deposition of amyloid proteins can lead to significant cardiac manifestations, including constrictive cardiomyopathy, heart failure (both preserved and reduced ejection fraction), and arrhythmias particularly atrial fibrillation, contributing to substantial morbidity and mortality. Diagnostic innovations, such as advanced imaging and novel biomarkers, have enabled early detection and precise subtype differentiation, underscoring the need for targeted therapies. Over the past decade, therapeutic advancements have introduced transformative medications that gained FDA approval for the management of transthyretin amyloidosis (ATTR) including transthyretin stabilizers and silencers. Promising strategies like gene editing, antisense oligonucleotides and monoclonal antibodies are currently under investigation. However, managing cardiac manifestations remains challenging, particularly in optimizing euvolemia and rate control in heart failure and atrial fibrillation with limitations in traditional medications. This review explores the evolving landscape of CA, from pathophysiologic insights to innovative therapies, and provides a comprehensive approach to the management of cardiac manifestations to address ongoing challenges this condition.
BACKGROUND: While Sodium glucose Co-transporter 2 inhibitors (SGLT2i) show proven benefits in heart failure with preserved ejection fraction (HFpEF), their role in transthyretin cardiac amyloidosis (ATTR-CA) remains unce...BACKGROUND: While Sodium glucose Co-transporter 2 inhibitors (SGLT2i) show proven benefits in heart failure with preserved ejection fraction (HFpEF), their role in transthyretin cardiac amyloidosis (ATTR-CA) remains uncertain. This meta-analysis evaluates SGLT2i efficacy and safety specifically in ATTR-CA patients, a population excluded from pivotal trials. MATERIALS AND METHODS: Following PRISMA guidelines, we systematically searched PubMed/Embase/Cochrane through December 2024 for studies assessing SGLT2i in cardiac amyloidosis. Primary outcomes included all-cause mortality, cardiovascular mortality, NT-proBNP levels, and hospitalizations. Risk Ratios (RR) and Hazard Ratios (HR) with 95 % confidence intervals (CIs) were used to compare treatment effects for categorical endpoints. Continuous outcomes were compared with mean differences (MD). RESULTS: Five observational studies (5101 patients; 2528 SGLT2i vs 2573 controls) met inclusion criteria. SGLT2i use was associated with significantly lower all-cause mortality (RR 0.37, 95 % CI 0.28-0.49, p < 0.00001, I²=12 %) and cardiovascular mortality (RR 0.30, 0.16-0.55, p < 0.00001, I²=25 %). NT-proBNP levels were significantly reduced (MD -299.66 pg/mL, -493.24 to -106.08, p = 0.002, I²=0 %) and hospitalization rates were significantly lower (HR 0,59, 95 %CI 0,38-0,90; p = 0,01, I=0 %). Most studies had moderate bias risk, primarily from retrospective designs and selection bias. CONCLUSIONS: In ATTR-CA patients, SGLT2i were associated with 63-70 % relative risk reduction in mortality and improved cardiac biomarkers and hospitalization rates. While promising, these observational findings require confirmation in randomized trials to address potential confounding factors.
Enhancer of zeste homolog 2 (EZH2), canonically recognized as an oncogenic driver through its histone methyltransferase activity, has emerged as a critical epigenetic orchestrator in cardiovascular pathophysiology with u...Enhancer of zeste homolog 2 (EZH2), canonically recognized as an oncogenic driver through its histone methyltransferase activity, has emerged as a critical epigenetic orchestrator in cardiovascular pathophysiology with unexpected functional complexity. While extensive oncological research has established EZH2's role in facilitating the Warburg effect and metabolic reprogramming in cancer cells, recent cardiovascular investigations reveal that EZH2 employs remarkably parallel mechanisms to coordinate the metabolic shift from oxidative phosphorylation to glycolysis during cardiac ischemia-a previously unrecognized molecular paradigm bridging cancer biology and cardiovascular pathophysiology. This review synthesizes emerging evidence demonstrating EZH2's unique context-dependent functionality in cardiac tissue, acting simultaneously as a transcriptional co-activator through non-canonical FOXM1 interaction and as an epigenetic repressor via its canonical PRC2-mediated H3K27 trimethylation activity. Most significantly, we highlight the novel discovery that EZH2 establishes a distinctive methylation landscape in ischemic cardiomyopathy through direct interaction with DNA methyltransferases, creating a molecular signature that suppresses cardioprotective factors like KLF15 while enhancing matrix metalloproteinase expression that drives adverse cardiac remodeling. Despite compelling preclinical evidence supporting EZH2 inhibition across multiple cardiovascular conditions, including atherosclerosis, cardiac hypertrophy, and myocardial fibrosis, a critical translational gap persists due to delivery limitations, potential off-target effects, and inadequate understanding of EZH2's temporal and tissue-specific functions. This review identifies crucial research opportunities, including developing cardiac-specific EZH2 modulators, exploring combination therapies targeting downstream pathways, and comprehensive interactome mapping to reveal cardiovascular-specific interactions. Decoding the complex regulatory networks governed by EZH2 across developmental stages and disease contexts represents a frontier for developing innovative epigenetic interventions addressing the global burden of cardiovascular disease.
Power dynamics may be defined as "a way different people or different groups of people interact with each other and where one of these sides is more powerful than the other one." Pronk et al. recently proposed an ecologi...Power dynamics may be defined as "a way different people or different groups of people interact with each other and where one of these sides is more powerful than the other one." Pronk et al. recently proposed an ecological framework for United States population health, identifying culture, politics, policy, and socioeconomics as forcing factors that drive variations in health behaviors, health conditions and ultimately health outcomes. The current analysis examines the percentage of individuals currently covered by Medicaid alone in the context of the forcing factors and health outcomes of the ecologic framework. Counties identified as aggressively individualistic had a significantly higher percentage of the population covered by Medicaid alone compared to all other groups. The percentage of the population covered by Medicaid alone was significantly correlated with all measures and outcomes within the ecological framework. Apart from the prevalence of binge drinking and cancer, all other measures and outcomes trended toward a less favorable pattern as the percentage of the county-level population covered by Medicaid alone increased. The potential for reductions in Medicaid funding represents a current political power dynamic. The current study indicates this power dynamic may have significant adverse consequences to the proposed ecological framework for health-the percentage of the population covered by Medicaid alone is related to an unfavorable phenotype across all forcing factors of the framework as well as health outcomes. Loss of Medicaid coverage has significant implications for further worsening population health.
Cardiac surgery is associated with significant postoperative pain, necessitating effective multimodal analgesia to reduce opioid-related morbidity. This systematic review and meta-analysis evaluated the analgesic efficac...Cardiac surgery is associated with significant postoperative pain, necessitating effective multimodal analgesia to reduce opioid-related morbidity. This systematic review and meta-analysis evaluated the analgesic efficacy of erector spinae plane block (ESPB) in adult cardiac surgery. Twenty-three randomized controlled trials (1,612 patients) were included. Primary outcomes revealed no significant difference in 24-hour postoperative coughing pain scores between ESPB and control groups (MD 0.12; 95 % CI:0.26 to 0.50; P = 0.54). However, ESPB demonstrated significant reductions in coughing and resting pain scores at 48 h (MD -0.60; 95 % CI:0.81to-0.38; P < 0.00001) and 72 h (MD -0.67; 95 % CI:1.02 to-0.33; P = 0.0001), alongside reduced 24-hour morphine consumption (MD -2.04; 95 % CI:2.46 to-1.61; P < 0.00001) and shorter mechanical ventilation duration (MD -26.53 minutes; 95 % CI:41.78 to-11.27; P = 0.0007). No differences were observed in ICU/hospital stays or surgical/anesthesia durations. Subgroup analyses highlighted variability in continuous versus single-shot ESPB techniques. High heterogeneity (I² >50 %) and moderate-to-low GRADE evidence underline the need for standardized protocols. ESPB shows promise in enhancing recovery by reducing opioid use and late-phase pain, though further high-quality trials are warranted.
Doxorubicin (DOX) remains a cornerstone chemotherapeutic agent despite its dose-dependent cardiotoxicity that can progress to irreversible dilated cardiomyopathy. At the same time, the mechanisms of DOX-induced cardiac i...Doxorubicin (DOX) remains a cornerstone chemotherapeutic agent despite its dose-dependent cardiotoxicity that can progress to irreversible dilated cardiomyopathy. At the same time, the mechanisms of DOX-induced cardiac injury are multifactorial, emerging evidence highlights circular RNAs (circRNAs) a unique class of covalently closed non-coding RNA molecules, as critical regulators of DOX cardiotoxicity. This review comprehensively examines the biogenesis and functional repertoire of circRNAs and their pivotal role in modulating DOX-induced cardiac damage. CircRNAs exert cardioprotective or cardiotoxic effects primarily through competitive endogenous RNA activity, RNA-binding protein interactions, translational products, and RNA N6-adenosine methylation-related mechanisms. Notably, the research gap lies in understanding how circRNAs orchestrate the complex interplay between five major regulated cell death pathways triggered by DOX: apoptosis, autophagy, necroptosis, ferroptosis, and pyroptosis. Additionally, circRNAs influence cellular processes underlying DOX-induced cardiomyocyte dysfunction, including oxidative stress, calcium handling defects, myocardial atrophy, thrombosis, and premature senescence. The novelty of this review lies in synthesizing evidence on circRNA-mediated regulatory networks across these diverse pathophysiological mechanisms, providing a theoretical foundation for developing circRNA-based diagnostic biomarkers and therapeutic interventions. Future research directions should focus on elucidating additional molecular mechanisms, validating circRNA-based biomarkers, and establishing translational frameworks for clinical applications to mitigate DOX cardiotoxicity while preserving its antitumor efficacy.