Previous
Cardio-oncology has emerged as a critical interdisciplinary field addressing the growing burden of cardiovascular complications arising from modern cancer therapies. While advances in chemotherapy, targeted agents, and immunotherapies have substantially improved cancer survival, they have concurrently led to a significant rise in cancer therapy-related cardiac dysfunction (CTRCD), contributing to increased long-term morbidity and mortality among cancer survivors. Conventional surveillance strategies often detect cardiotoxicity only after irreversible myocardial injury has occurred, accentuating the need for more precise, proactive, and personalized approaches. Theranostics, integrating diagnostic imaging, molecular biomarkers, and targeted therapeutics, offers a promising paradigm to enable early detection, risk stratification, and tailored cardioprotective interventions in cardio-oncology. This review synthesizes recent advances in theranostic strategies relevant to cardio-oncology, spanning imaging-based, biomarker-driven, and nanotechnology-enabled approaches. Advanced imaging modalities such as hybrid PET/MRI, AI-enhanced echocardiography, and novel molecular radiotracers [e.g., 68Ga-FAPI, 18F-DHMT, [68Ga]pentixafor] enable early identification of subclinical myocardial injury, inflammation, fibrosis, and metabolic dysfunction before overt declines in left ventricular ejection fraction occur. Complementing imaging, biomarker-driven theranostics including high-sensitivity cardiac troponins, natriuretic peptides, circulating and exosomal microRNAs, and cardiomyocyte-specific cell-free DNA, provide minimally invasive, real-time insights into myocardial stress, injury, and immune-mediated cardiotoxicity. Nanotheranostic platforms, such as liposomal doxorubicin and immunomodulatory nanoparticles, further enhance therapeutic precision by reducing off-target cardiac exposure while preserving antitumor efficacy. Despite these advances, clinical translation remains hindered by interdisciplinary fragmentation, limited access to advanced infrastructure, high development costs, regulatory heterogeneity between agencies, and reliance on surrogate endpoints rather than long-term cardiovascular outcomes. Theranostics represents a transformative approach in cardio-oncology. Integration of advanced imaging, molecular biomarkers, artificial intelligence, and nanotechnology holds significant promise for preserving cardiac health without compromising oncologic success. Embedding theranostic strategies into routine cardio-oncology practice is essential to advancing precision medicine and improving cardiovascular outcomes for cancer patients worldwide.
Cardio-oncology has emerged as a critical interdisciplinary field addressing the growing burden of cardiovascular complications arising from modern cancer therapies. While advances in chemotherapy, targeted agents, and immunotherapies have substantially improved cancer survival, they have concurrently led to a significant rise in cancer therapy-related cardiac dysfunction (CTRCD), contributing to increased long-term morbidity and mortality among cancer survivors. Conventional surveillance strategies often detect cardiotoxicity only after irreversible myocardial injury has occurred, accentuating the need for more precise, proactive, and personalized approaches. Theranostics, integrating diagnostic imaging, molecular biomarkers, and targeted therapeutics, offers a promising paradigm to enable early detection, risk stratification, and tailored cardioprotective interventions in cardio-oncology. This review synthesizes recent advances in theranostic strategies relevant to cardio-oncology, spanning imaging-based, biomarker-driven, and nanotechnology-enabled approaches. Advanced imaging modalities such as hybrid PET/MRI, AI-enhanced echocardiography, and novel molecular radiotracers [e.g., 68Ga-FAPI, 18F-DHMT, [68Ga]pentixafor] enable early identification of subclinical myocardial injury, inflammation, fibrosis, and metabolic dysfunction before overt declines in left ventricular ejection fraction occur. Complementing imaging, biomarker-driven theranostics including high-sensitivity cardiac troponins, natriuretic peptides, circulating and exosomal microRNAs, and cardiomyocyte-specific cell-free DNA, provide minimally invasive, real-time insights into myocardial stress, injury, and immune-mediated cardiotoxicity. Nanotheranostic platforms, such as liposomal doxorubicin and immunomodulatory nanoparticles, further enhance therapeutic precision by reducing off-target cardiac exposure while preserving antitumor efficacy. Despite these advances, clinical translation remains hindered by interdisciplinary fragmentation, limited access to advanced infrastructure, high development costs, regulatory heterogeneity between agencies, and reliance on surrogate endpoints rather than long-term cardiovascular outcomes. Theranostics represents a transformative approach in cardio-oncology. Integration of advanced imaging, molecular biomarkers, artificial intelligence, and nanotechnology holds significant promise for preserving cardiac health without compromising oncologic success. Embedding theranostic strategies into routine cardio-oncology practice is essential to advancing precision medicine and improving cardiovascular outcomes for cancer patients worldwide.
DOI: https://doi.org/10.37349/ec.2026.1012128
Modern bodybuilding and aesthetic physique sports have become increasingly associated with cardiovascular morbidity and sudden cardiac death. Although anabolic-androgenic steroids are frequently implicated in bodybuilding-associated cardiotoxicity, contemporary physique-enhancement practices commonly involve complex polypharmacy regimens including growth hormone, insulin, stimulants, thyroid hormones, and diuretics, often combined with extreme dehydration and electrolyte manipulation during contest preparation. This narrative review summarizes the current evidence regarding cardiovascular remodeling, cardiotoxicity, and sudden cardiac death in competitive bodybuilders. Chronic exposure to performance-enhancing substances may contribute to pathological left ventricular hypertrophy, myocardial fibrosis, endothelial dysfunction, thrombogenesis, dyslipidemia, autonomic imbalance, and electrical remodeling. In addition, acute stressors during “peak week,” including dehydration, stimulant use, and electrolyte disturbances, may trigger fatal arrhythmias or ischemic events in susceptible individuals. Autopsy and imaging studies have reported structural and functional cardiac abnormalities consistent with maladaptive remodeling, while recent epidemiological evidence suggests elevated mortality rates among professional bodybuilders. Overall, cardiovascular risk in modern bodybuilding appears to extend beyond isolated anabolic-androgenic steroid exposure and likely reflects a complex interaction between chronic myocardial injury, polypharmacy, metabolic instability, and extreme physiological manipulation practices. Increased cardiovascular awareness and individualized cardiovascular surveillance strategies may help identify high-risk individuals and potentially reduce cardiovascular morbidity and mortality in competitive bodybuilders.
Modern bodybuilding and aesthetic physique sports have become increasingly associated with cardiovascular morbidity and sudden cardiac death. Although anabolic-androgenic steroids are frequently implicated in bodybuilding-associated cardiotoxicity, contemporary physique-enhancement practices commonly involve complex polypharmacy regimens including growth hormone, insulin, stimulants, thyroid hormones, and diuretics, often combined with extreme dehydration and electrolyte manipulation during contest preparation. This narrative review summarizes the current evidence regarding cardiovascular remodeling, cardiotoxicity, and sudden cardiac death in competitive bodybuilders. Chronic exposure to performance-enhancing substances may contribute to pathological left ventricular hypertrophy, myocardial fibrosis, endothelial dysfunction, thrombogenesis, dyslipidemia, autonomic imbalance, and electrical remodeling. In addition, acute stressors during “peak week,” including dehydration, stimulant use, and electrolyte disturbances, may trigger fatal arrhythmias or ischemic events in susceptible individuals. Autopsy and imaging studies have reported structural and functional cardiac abnormalities consistent with maladaptive remodeling, while recent epidemiological evidence suggests elevated mortality rates among professional bodybuilders. Overall, cardiovascular risk in modern bodybuilding appears to extend beyond isolated anabolic-androgenic steroid exposure and likely reflects a complex interaction between chronic myocardial injury, polypharmacy, metabolic instability, and extreme physiological manipulation practices. Increased cardiovascular awareness and individualized cardiovascular surveillance strategies may help identify high-risk individuals and potentially reduce cardiovascular morbidity and mortality in competitive bodybuilders.
DOI: https://doi.org/10.37349/ec.2026.1012127
Aim:
Cardiovascular disease (CVD) is the most common non-cancer cause of death in breast cancer (BC) survivors, yet the age-specific point at which CVD deaths overtake BC deaths, and its early indicators, remain unknown. This study aimed to establish this time point and identify factors associated with cardiovascular-specific mortality (CSM) in early-stage BC.
Methods:
We analyzed 255,731 women diagnosed with stage I–III BC (2010–2020) from the Surveillance, Epidemiology, and End Results (SEER) 17 registries. CSM was compared with the general United States (US) female population using standardized mortality ratio (SMR) via Centers for Disease Control and Prevention’s Wide-ranging Online Data for Epidemiologic Research (CDC WONDER). Competing-risk methods estimated cumulative incidence, and Fine-Gray regression identified factors associated with CSM after adjustment for measured covariates.
Results:
Upon age standardization, the overall risk of CSM was modestly higher among BC patients than in the general female population [SMR = 1.16, 95% confidence intervals (CI): 1.13–1.19, P < 0.001], with marked heterogeneity by age; the relative excess was greatest in women aged < 50 (SMR = 2.894) and attenuated in older strata (50–59, SMR = 1.138; 60–69, SMR = 1.208; 70–85, SMR = 1.128). Cumulative CSM reached 2.53% at 84 months (7 years). Within the oldest cohort (70–85 years), cumulative CSM crossed above BC-specific mortality later, at approximately 8 years (97 months; 95% CI 91–101) [sub-distribution hazard ratio (SHR) = 19.37; 70–85 vs. 18–49], followed by unmarried status (1.59), Black race (1.37), advanced tumor (T4, 1.60) and nodal stage (N3, 1.34). Chemotherapy and radiotherapy were associated with lower CSM (SHR = 0.59 and 0.64); given SEER’s lack of treatment data, these likely reflect selection bias and residual confounding rather than protection.
Conclusions:
This is one of the first studies to identify an approximate mortality crossover point between CSM and BC-specific mortality at about 8 years (97 months) in women aged 70–85, providing a clinically relevant, exploratory time point for increased cardiovascular monitoring in this high-risk population.
Aim:
Cardiovascular disease (CVD) is the most common non-cancer cause of death in breast cancer (BC) survivors, yet the age-specific point at which CVD deaths overtake BC deaths, and its early indicators, remain unknown. This study aimed to establish this time point and identify factors associated with cardiovascular-specific mortality (CSM) in early-stage BC.
Methods:
We analyzed 255,731 women diagnosed with stage I–III BC (2010–2020) from the Surveillance, Epidemiology, and End Results (SEER) 17 registries. CSM was compared with the general United States (US) female population using standardized mortality ratio (SMR) via Centers for Disease Control and Prevention’s Wide-ranging Online Data for Epidemiologic Research (CDC WONDER). Competing-risk methods estimated cumulative incidence, and Fine-Gray regression identified factors associated with CSM after adjustment for measured covariates.
Results:
Upon age standardization, the overall risk of CSM was modestly higher among BC patients than in the general female population [SMR = 1.16, 95% confidence intervals (CI): 1.13–1.19, P < 0.001], with marked heterogeneity by age; the relative excess was greatest in women aged < 50 (SMR = 2.894) and attenuated in older strata (50–59, SMR = 1.138; 60–69, SMR = 1.208; 70–85, SMR = 1.128). Cumulative CSM reached 2.53% at 84 months (7 years). Within the oldest cohort (70–85 years), cumulative CSM crossed above BC-specific mortality later, at approximately 8 years (97 months; 95% CI 91–101) [sub-distribution hazard ratio (SHR) = 19.37; 70–85 vs. 18–49], followed by unmarried status (1.59), Black race (1.37), advanced tumor (T4, 1.60) and nodal stage (N3, 1.34). Chemotherapy and radiotherapy were associated with lower CSM (SHR = 0.59 and 0.64); given SEER’s lack of treatment data, these likely reflect selection bias and residual confounding rather than protection.
Conclusions:
This is one of the first studies to identify an approximate mortality crossover point between CSM and BC-specific mortality at about 8 years (97 months) in women aged 70–85, providing a clinically relevant, exploratory time point for increased cardiovascular monitoring in this high-risk population.
DOI: https://doi.org/10.37349/ec.2026.1012126
Extracorporeal membrane oxygenation (ECMO) is a life-saving intervention for patients with refractory cardiac or respiratory failure. Complications associated with ECMO include bleeding, thrombosis, and coagulopathy. Overt disseminated intravascular coagulation (DIC) in ECMO patients is a rare but severe complication, yet its presentation, timing, and outcomes remain poorly portrayed in the literature. We present a case series of three patients who developed overt DIC while receiving veno-arterial (V-A ECMO) or veno-venous (V-V ECMO) at a tertiary academic medical center between 2023 and 2025. Overt DIC was diagnosed using the International Society on Thrombosis and Haemostasis (ISTH) scoring system, with scores ≥ 5 considered diagnostic. All patients met the ISTH criteria for overt DIC during ECMO support upon case review. Laboratory findings demonstrated severe thrombocytopenia, prolonged prothrombin time (PT)/international normalized ratio (INR), and hypofibrinogenemia. Despite supportive management, including blood product replacement, targeted anticoagulation adjustments, and correction of underlying triggers, overall, 2 out of 3 patients in the series died during their index hospital admissions. Overt DIC during ECMO is a life-threatening complication associated with risk of bleeding and poor prognosis. These cases emphasize the importance of vigilance for early indicators of impending DIC, including thrombus formation within the ECMO oxygenator or circuit. Once identified, a timely oxygenator exchange may improve circuit performance and oxygenation, potentially limiting further activation of the coagulation cascade. Urgent decannulation should be considered when extracorporeal support is no longer essential for survival. In conclusion, these cases highlight the importance of early recognition and multidisciplinary management of ECMO-associated DIC and support the need for further research to develop strong evidence-based strategies for prevention and treatment.
Extracorporeal membrane oxygenation (ECMO) is a life-saving intervention for patients with refractory cardiac or respiratory failure. Complications associated with ECMO include bleeding, thrombosis, and coagulopathy. Overt disseminated intravascular coagulation (DIC) in ECMO patients is a rare but severe complication, yet its presentation, timing, and outcomes remain poorly portrayed in the literature. We present a case series of three patients who developed overt DIC while receiving veno-arterial (V-A ECMO) or veno-venous (V-V ECMO) at a tertiary academic medical center between 2023 and 2025. Overt DIC was diagnosed using the International Society on Thrombosis and Haemostasis (ISTH) scoring system, with scores ≥ 5 considered diagnostic. All patients met the ISTH criteria for overt DIC during ECMO support upon case review. Laboratory findings demonstrated severe thrombocytopenia, prolonged prothrombin time (PT)/international normalized ratio (INR), and hypofibrinogenemia. Despite supportive management, including blood product replacement, targeted anticoagulation adjustments, and correction of underlying triggers, overall, 2 out of 3 patients in the series died during their index hospital admissions. Overt DIC during ECMO is a life-threatening complication associated with risk of bleeding and poor prognosis. These cases emphasize the importance of vigilance for early indicators of impending DIC, including thrombus formation within the ECMO oxygenator or circuit. Once identified, a timely oxygenator exchange may improve circuit performance and oxygenation, potentially limiting further activation of the coagulation cascade. Urgent decannulation should be considered when extracorporeal support is no longer essential for survival. In conclusion, these cases highlight the importance of early recognition and multidisciplinary management of ECMO-associated DIC and support the need for further research to develop strong evidence-based strategies for prevention and treatment.
DOI: https://doi.org/10.37349/ec.2026.1012125
Background:
Cardiovascular disease is the leading cause of mortality globally, with its impact escalating swiftly throughout Africa. Periodontitis, a widespread chronic inflammatory condition, is a recognized correlate of cardiovascular disease in high-income countries; however, evidence from Africa remains unsynthesised. This scoping review systematically examined the existing evidence concerning the local and systemic associations between periodontitis and cardiovascular disease in African populations, evaluated their implications for causal plausibility, and identified key research gaps requiring attention.
Methods:
The review followed the Joanna Briggs Institute methodology and was reported in accordance with the PRISMA Extension for Scoping Reviews. Eligible sources were primary studies conducted in African populations that reported a measure of periodontal status together with a cardiovascular or cardiometabolic outcome, risk indicator, or related care construct. MEDLINE (PubMed), Scopus, Web of Science, and African Journals Online were searched from inception to June 2026. Records were independently screened by two reviewers, with disagreements resolved by a third reviewer; findings were charted and synthesised using descriptive methods.
Results:
Only seven primary studies, concentrated in Cameroon, Nigeria, and Rwanda, met the eligibility criteria. The studies were predominantly cross-sectional and hospital-based. Reported associations aligned with the global literature, particularly for hypertension and cardiometabolic risk; however, periodontal exposure was defined inconsistently and few studies adjusted fully for shared risk factors. No interventional study with a cardiovascular endpoint and no prospective cohort was identified.
Discussion:
African research on the periodontitis and cardiovascular disease association is limited, predominantly cross-sectional, and concentrated in a few countries. Causal plausibility therefore cannot be adequately assessed from the current evidence, which is dominated by seven cross-sectional studies. Given that the region carries one of the highest periodontitis burdens globally alongside a rising cardiovascular burden, longitudinal and interventional research and integrated oral and cardiovascular care should be prioritised.
Background:
Cardiovascular disease is the leading cause of mortality globally, with its impact escalating swiftly throughout Africa. Periodontitis, a widespread chronic inflammatory condition, is a recognized correlate of cardiovascular disease in high-income countries; however, evidence from Africa remains unsynthesised. This scoping review systematically examined the existing evidence concerning the local and systemic associations between periodontitis and cardiovascular disease in African populations, evaluated their implications for causal plausibility, and identified key research gaps requiring attention.
Methods:
The review followed the Joanna Briggs Institute methodology and was reported in accordance with the PRISMA Extension for Scoping Reviews. Eligible sources were primary studies conducted in African populations that reported a measure of periodontal status together with a cardiovascular or cardiometabolic outcome, risk indicator, or related care construct. MEDLINE (PubMed), Scopus, Web of Science, and African Journals Online were searched from inception to June 2026. Records were independently screened by two reviewers, with disagreements resolved by a third reviewer; findings were charted and synthesised using descriptive methods.
Results:
Only seven primary studies, concentrated in Cameroon, Nigeria, and Rwanda, met the eligibility criteria. The studies were predominantly cross-sectional and hospital-based. Reported associations aligned with the global literature, particularly for hypertension and cardiometabolic risk; however, periodontal exposure was defined inconsistently and few studies adjusted fully for shared risk factors. No interventional study with a cardiovascular endpoint and no prospective cohort was identified.
Discussion:
African research on the periodontitis and cardiovascular disease association is limited, predominantly cross-sectional, and concentrated in a few countries. Causal plausibility therefore cannot be adequately assessed from the current evidence, which is dominated by seven cross-sectional studies. Given that the region carries one of the highest periodontitis burdens globally alongside a rising cardiovascular burden, longitudinal and interventional research and integrated oral and cardiovascular care should be prioritised.
DOI: https://doi.org/10.37349/ec.2026.1012124
This article belongs to the special issue Periodontitis and cardiovascular disease: local and systemic links
Medical radiation exposure in cardiology represents a significant and often underappreciated component of patient risk, with profound implications for individual and population health. Ionizing radiation is a proven carcinogen even at low doses, yet awareness among prescribers and practitioners remains suboptimal. Cardiologists are responsible for approximately half of all medical radiation exposure, with cumulative doses exceeding 100 mSv in one out of five adult cardiology patients and children with congenital heart disease—equivalent to 5,000 chest X-rays and corresponding to one excess cancer per 100 exposed individuals. Radiation exposure also contributes to non-cancer risks, including accelerated atherosclerosis, through mechanisms involving DNA instability and chronic inflammation. Professional exposure among interventional cardiologists is 4–5 times higher than that of diagnostic radiologists, with documented increases in chromosomal aberrations and vascular disease. Current guidelines emphasize justification, optimization, and education as cornerstones of radiation safety. Technological advances have enabled substantial dose reductions across all imaging modalities, and non-ionizing alternatives such as echocardiography and cardiac magnetic resonance offer effective diagnostic options without carcinogenic risk. This review examines the scope of radiation exposure in cardiology, associated cancer and non-cancer risks, current guideline recommendations, and strategies for achieving radiologic sustainability through responsible imaging practices.
Medical radiation exposure in cardiology represents a significant and often underappreciated component of patient risk, with profound implications for individual and population health. Ionizing radiation is a proven carcinogen even at low doses, yet awareness among prescribers and practitioners remains suboptimal. Cardiologists are responsible for approximately half of all medical radiation exposure, with cumulative doses exceeding 100 mSv in one out of five adult cardiology patients and children with congenital heart disease—equivalent to 5,000 chest X-rays and corresponding to one excess cancer per 100 exposed individuals. Radiation exposure also contributes to non-cancer risks, including accelerated atherosclerosis, through mechanisms involving DNA instability and chronic inflammation. Professional exposure among interventional cardiologists is 4–5 times higher than that of diagnostic radiologists, with documented increases in chromosomal aberrations and vascular disease. Current guidelines emphasize justification, optimization, and education as cornerstones of radiation safety. Technological advances have enabled substantial dose reductions across all imaging modalities, and non-ionizing alternatives such as echocardiography and cardiac magnetic resonance offer effective diagnostic options without carcinogenic risk. This review examines the scope of radiation exposure in cardiology, associated cancer and non-cancer risks, current guideline recommendations, and strategies for achieving radiologic sustainability through responsible imaging practices.
DOI: https://doi.org/10.37349/ec.2026.1012123
Background:
The cardiovascular risk and patient management are evaluated on the basis of risk scores that account for the multifactorial risk factors and thus fail in the estimation of an individual’s cardiovascular disease (CVD) risk. Advances in the field of medical imaging, especially cardiac computed tomography angiography (CTA) and magnetic resonance imaging (MRI), have laid the foundation of radiogenomics.
Methods:
Research from the past 10 years was collected using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology from PubMed, Google Scholar, ScienceDirect, and MEDLINE, and some additional sources like websites and arXiv.
Results:
A total of 860 records were identified, and after the removal of duplicates, 800 remained for the screening for relevance by the abstracts and titles. After screening, 225 articles were assessed for eligibility, and the records that were either out of scope, had insufficient data, or were neither written nor translated in English were excluded. Finally, 80 records were identified to be included in the current review.
Discussion:
We speculated on the application of artificial intelligence (AI) algorithms to identify CVD and its prognosis. Radiomic features, which are extracted by CTA and MRI, have shown great diagnostic accuracy of coronary plaques, and on the other hand, some studies exploited radiogenomics integration, which suggests that further research needs to be done in this field.
Background:
The cardiovascular risk and patient management are evaluated on the basis of risk scores that account for the multifactorial risk factors and thus fail in the estimation of an individual’s cardiovascular disease (CVD) risk. Advances in the field of medical imaging, especially cardiac computed tomography angiography (CTA) and magnetic resonance imaging (MRI), have laid the foundation of radiogenomics.
Methods:
Research from the past 10 years was collected using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology from PubMed, Google Scholar, ScienceDirect, and MEDLINE, and some additional sources like websites and arXiv.
Results:
A total of 860 records were identified, and after the removal of duplicates, 800 remained for the screening for relevance by the abstracts and titles. After screening, 225 articles were assessed for eligibility, and the records that were either out of scope, had insufficient data, or were neither written nor translated in English were excluded. Finally, 80 records were identified to be included in the current review.
Discussion:
We speculated on the application of artificial intelligence (AI) algorithms to identify CVD and its prognosis. Radiomic features, which are extracted by CTA and MRI, have shown great diagnostic accuracy of coronary plaques, and on the other hand, some studies exploited radiogenomics integration, which suggests that further research needs to be done in this field.
DOI: https://doi.org/10.37349/ec.2026.1012122
Aim:
Valvular heart disease (VHD) is an important factor in cardiovascular mortality. While early diagnosis is essential, existing methods often lack accuracy, leading to misdiagnosis. This study explores the use of deep learning (DL) for multi-class classification of VHD using phonocardiograph (PCG) signals.
Methods:
The dataset includes normal PCG heart signals and nine VHD classes such as severe and mild aortic stenosis, mild and moderate mitral stenosis, mild, moderate, and severe mitral regurgitation, and moderate and severe tricuspid regurgitation. A novel convolutional neural network (CNN) is developed to classify these ten classes, demonstrating high accuracy even in noisy data acquisition. Unlike traditional machine learning, which relies on handcrafted features such as spectral, wavelet, and mel-frequency cepstral coefficients, the CNN model automatically learns patterns from raw signals, thereby reducing the need for manual feature engineering. The model is further validated using real-time PCG data from heart clinics diagnosed by heart specialists.
Results:
It achieves excellent performance with 99.81% accuracy, 99.84% precision, 99.82% recall, 99.85% F1-score, and an area under the curve of the receiver operating characteristic of 1.0.
Conclusions:
This DL model eliminates segmentation and manual pre-processing, enabling early, accurate VHD detection while outperforming existing methods and supporting clinical decisions and patient care.
Aim:
Valvular heart disease (VHD) is an important factor in cardiovascular mortality. While early diagnosis is essential, existing methods often lack accuracy, leading to misdiagnosis. This study explores the use of deep learning (DL) for multi-class classification of VHD using phonocardiograph (PCG) signals.
Methods:
The dataset includes normal PCG heart signals and nine VHD classes such as severe and mild aortic stenosis, mild and moderate mitral stenosis, mild, moderate, and severe mitral regurgitation, and moderate and severe tricuspid regurgitation. A novel convolutional neural network (CNN) is developed to classify these ten classes, demonstrating high accuracy even in noisy data acquisition. Unlike traditional machine learning, which relies on handcrafted features such as spectral, wavelet, and mel-frequency cepstral coefficients, the CNN model automatically learns patterns from raw signals, thereby reducing the need for manual feature engineering. The model is further validated using real-time PCG data from heart clinics diagnosed by heart specialists.
Results:
It achieves excellent performance with 99.81% accuracy, 99.84% precision, 99.82% recall, 99.85% F1-score, and an area under the curve of the receiver operating characteristic of 1.0.
Conclusions:
This DL model eliminates segmentation and manual pre-processing, enabling early, accurate VHD detection while outperforming existing methods and supporting clinical decisions and patient care.
DOI: https://doi.org/10.37349/ec.2026.1012121
Parturients with pulmonary arterial hypertension (PAH) face an increased risk of morbidity and mortality surrounding the peripartum period. Patients with severe PAH and Eisenmenger syndrome have the highest risk for perioperative mortality and provide a significant perioperative challenge for anesthesiologists, necessitating a multidisciplinary approach throughout pregnancy. We present a case of an urgent cesarean section at 37 weeks of gestation in a patient with Eisenmenger syndrome, a large atrial septal defect, and supra-systemic pulmonary hypertension. Due to the patient’s severity of PAH, cardiothoracic surgery was present and placed femoral arterial and venous catheters in preparation for possible extracorporeal membrane oxygenation (ECMO) cannulation in the event of hemodynamic collapse. The procedure was performed under a carefully titrated epidural, thus avoiding general anesthesia and the dangers associated with inducing a patient with her comorbid conditions. An arterial line, internal jugular central line, and Swan-Ganz catheter were placed while the patient was awake to aid in monitoring. Additionally, transthoracic echocardiography (TTE) was used to assist in cardiac monitoring while the epidural level was gradually increased. She was maintained on vasopressin, epinephrine, and phenylephrine infusions in addition to inhaled nitric oxide. She tolerated the procedure well, and the fetus was delivered safely. Careful management across pre-epidural, post-epidural, intraoperative, and postoperative stages illustrates the dynamic adjustments and multidisciplinary communication required in this patient population. Advanced medical therapy optimization, careful neuraxial anesthesia titration, and early consideration of extracorporeal cardiopulmonary resuscitation (ECPR) together capture the critical elements of management in this complex setting.
Parturients with pulmonary arterial hypertension (PAH) face an increased risk of morbidity and mortality surrounding the peripartum period. Patients with severe PAH and Eisenmenger syndrome have the highest risk for perioperative mortality and provide a significant perioperative challenge for anesthesiologists, necessitating a multidisciplinary approach throughout pregnancy. We present a case of an urgent cesarean section at 37 weeks of gestation in a patient with Eisenmenger syndrome, a large atrial septal defect, and supra-systemic pulmonary hypertension. Due to the patient’s severity of PAH, cardiothoracic surgery was present and placed femoral arterial and venous catheters in preparation for possible extracorporeal membrane oxygenation (ECMO) cannulation in the event of hemodynamic collapse. The procedure was performed under a carefully titrated epidural, thus avoiding general anesthesia and the dangers associated with inducing a patient with her comorbid conditions. An arterial line, internal jugular central line, and Swan-Ganz catheter were placed while the patient was awake to aid in monitoring. Additionally, transthoracic echocardiography (TTE) was used to assist in cardiac monitoring while the epidural level was gradually increased. She was maintained on vasopressin, epinephrine, and phenylephrine infusions in addition to inhaled nitric oxide. She tolerated the procedure well, and the fetus was delivered safely. Careful management across pre-epidural, post-epidural, intraoperative, and postoperative stages illustrates the dynamic adjustments and multidisciplinary communication required in this patient population. Advanced medical therapy optimization, careful neuraxial anesthesia titration, and early consideration of extracorporeal cardiopulmonary resuscitation (ECPR) together capture the critical elements of management in this complex setting.
DOI: https://doi.org/10.37349/ec.2026.1012119
This article belongs to the special issue Cardiovascular Risk for Mothers and Offspring Resulting from Complicated Pregnancy
Background:
Chronic kidney disease (CKD) is linked to high cardiovascular morbidity and mortality. Many patients remain at risk despite standard treatment. This review assessed the renal, cardiovascular, safety, and primary care implementation outcomes of sodium-glucose cotransporter-2 (SGLT2) inhibitors in CKD, including patients with and without diabetes.
Methods:
This systematic review followed PRISMA 2020 guidelines. PubMed, Scopus, and Google Scholar were searched for English-language human studies published between 2016 and 2026. Reference lists of eligible articles were also manually screened. Eligible studies included randomized controlled trials and primary observational studies evaluating SGLT2 inhibitors in patients with CKD, with or without diabetes. Studies reporting renal, cardiovascular, safety, or primary care implementation outcomes were included. Data were extracted using a standardized form and synthesized qualitatively because of clinical and methodological heterogeneity.
Results:
Fifteen primary studies were included, comprising randomized controlled trials and observational studies. Across landmark clinical trials and real-world studies, SGLT2 inhibitors slowed eGFR decline, reduced albuminuria, and lowered the risk of kidney and heart failure hospitalization. Renal and cardiovascular benefits were observed in patients with and without diabetes. SGLT2 inhibitors were generally well tolerated, with genital mycotic infections and volume depletion being the most reported adverse events, while serious adverse events were uncommon. Real-world studies consistently identified underprescription and implementation barriers in primary care.
Discussion:
SGLT2 inhibitors are foundational therapies for CKD, providing consistent renal and cardiovascular benefits with an acceptable safety profile in patients with and without diabetes. However, substantial gaps remain in their implementation in primary care. Improving early identification of eligible patients, clinician awareness, and integration of guideline-directed prescribing into routine practice may help reduce CKD progression and cardiovascular events.
Background:
Chronic kidney disease (CKD) is linked to high cardiovascular morbidity and mortality. Many patients remain at risk despite standard treatment. This review assessed the renal, cardiovascular, safety, and primary care implementation outcomes of sodium-glucose cotransporter-2 (SGLT2) inhibitors in CKD, including patients with and without diabetes.
Methods:
This systematic review followed PRISMA 2020 guidelines. PubMed, Scopus, and Google Scholar were searched for English-language human studies published between 2016 and 2026. Reference lists of eligible articles were also manually screened. Eligible studies included randomized controlled trials and primary observational studies evaluating SGLT2 inhibitors in patients with CKD, with or without diabetes. Studies reporting renal, cardiovascular, safety, or primary care implementation outcomes were included. Data were extracted using a standardized form and synthesized qualitatively because of clinical and methodological heterogeneity.
Results:
Fifteen primary studies were included, comprising randomized controlled trials and observational studies. Across landmark clinical trials and real-world studies, SGLT2 inhibitors slowed eGFR decline, reduced albuminuria, and lowered the risk of kidney and heart failure hospitalization. Renal and cardiovascular benefits were observed in patients with and without diabetes. SGLT2 inhibitors were generally well tolerated, with genital mycotic infections and volume depletion being the most reported adverse events, while serious adverse events were uncommon. Real-world studies consistently identified underprescription and implementation barriers in primary care.
Discussion:
SGLT2 inhibitors are foundational therapies for CKD, providing consistent renal and cardiovascular benefits with an acceptable safety profile in patients with and without diabetes. However, substantial gaps remain in their implementation in primary care. Improving early identification of eligible patients, clinician awareness, and integration of guideline-directed prescribing into routine practice may help reduce CKD progression and cardiovascular events.
DOI: https://doi.org/10.37349/ec.2026.1012120
Aim:
Allostatic load (AL) is a composite measure of cumulative physiological stress, but its role in heart failure (HF) onset and prognosis remains unclear.
Methods:
We analyzed data from two U.S. cohorts. Logistic regression assessed AL and incident HF in 3,814 adults from the Health and Retirement Study (HRS, 2016–2020). Cox regression examined AL with cardiovascular and all-cause mortality in 1,200 HF patients from the National Health and Nutrition Examination Survey (NHANES, 1999–2010 and 2015–2016). AL was derived from nine biomarkers and categorized as low (0–2), medium (3), or high (≥ 4).
Results:
In HRS, after full adjustment, high AL was associated with increased incident HF risk versus low AL (OR = 2.07; 95% CI: 1.29–3.32; P = 0.002), with each 1-unit increase raising risk by 30% (P < 0.001). In NHANES, after full adjustment, high AL predicted elevated cardiovascular (HR = 2.03; 95% CI: 1.37–3.03; P < 0.001) and all-cause mortality (HR = 1.70; 95% CI: 1.30–2.22; P < 0.001). Per unit increase, AL raised cardiovascular mortality by 18% and all-cause mortality by 15%. Model performance improved modestly with AL.
Conclusions:
Elevated AL is independently associated with HF incidence and poorer prognosis, supporting its potential as an integrative biomarker for HF risk stratification and prevention.
Aim:
Allostatic load (AL) is a composite measure of cumulative physiological stress, but its role in heart failure (HF) onset and prognosis remains unclear.
Methods:
We analyzed data from two U.S. cohorts. Logistic regression assessed AL and incident HF in 3,814 adults from the Health and Retirement Study (HRS, 2016–2020). Cox regression examined AL with cardiovascular and all-cause mortality in 1,200 HF patients from the National Health and Nutrition Examination Survey (NHANES, 1999–2010 and 2015–2016). AL was derived from nine biomarkers and categorized as low (0–2), medium (3), or high (≥ 4).
Results:
In HRS, after full adjustment, high AL was associated with increased incident HF risk versus low AL (OR = 2.07; 95% CI: 1.29–3.32; P = 0.002), with each 1-unit increase raising risk by 30% (P < 0.001). In NHANES, after full adjustment, high AL predicted elevated cardiovascular (HR = 2.03; 95% CI: 1.37–3.03; P < 0.001) and all-cause mortality (HR = 1.70; 95% CI: 1.30–2.22; P < 0.001). Per unit increase, AL raised cardiovascular mortality by 18% and all-cause mortality by 15%. Model performance improved modestly with AL.
Conclusions:
Elevated AL is independently associated with HF incidence and poorer prognosis, supporting its potential as an integrative biomarker for HF risk stratification and prevention.
DOI: https://doi.org/10.37349/ec.2026.1012118
Pembrolizumab, a programmed cell death protein 1 inhibitor, has had a substantial impact on cancer treatment across multiple malignancies, but is associated with immune-related cardiovascular toxicities that pose significant clinical challenges. Complications such as myocarditis, arrhythmias, and cardiomyopathy are emerging as significant entities with high morbidity and mortality. This article is a narrative review and was not designed or conducted as a systematic review. No formal systematic review protocol was followed and attempts to identify or include all published studies on this topic were not undertaken. The goal is to provide a clinically oriented synthesis of the current literature on pembrolizumab-associated cardiotoxicity. A literature search was conducted using PubMed, Medline, and Google Scholar databases for articles published between January 2014 and March 2025. Search terms included ‘pembrolizumab,’ ‘PD-1 inhibitor,’ ‘immune checkpoint inhibitor,’ ‘cardiotoxicity,’ ‘myocarditis,’ ‘pericarditis,’ ‘arrhythmia,’ and ‘cardiac adverse events,’ used individually and in combination. Inclusion criteria encompassed English-language clinical trials, observational studies, systematic reviews, meta-analyses, pharmacovigilance analyses, clinical practice guidelines, and case reports involving human subjects. Non-English publications, preclinical studies without clinical correlates, and editorials without original data were excluded. Reference lists of identified articles were manually reviewed to identify additional relevant publications. Study selection was performed by a single author. Pembrolizumab-induced myocarditis, although rare, carries a high mortality rate and typically presents within the first few weeks of treatment, including a relative risk of myocarditis ~4.5 with combination immune checkpoint inhibitor therapy. Proposed mechanisms of this cardiotoxicity, though not settled, include shared antigenic targets between tumor and cardiac tissue and impaired immune tolerance. Current management relies on prompt recognition, immunosuppression with high-dose IV methylprednisolone as first-line therapy, and additional immunomodulatory agents for refractory cases. Emerging evidence from case reports and small cohort studies suggests potential benefit from abatacept with ruxolitinib in steroid-refractory cases; however, prospective validation is needed. Baseline cardiac screening and serial monitoring of cardiac biomarkers including high-sensitivity troponin and NT-proBNP, and a multidisciplinary cardio-oncology approach are essential for early detection and optimal outcomes.
Pembrolizumab, a programmed cell death protein 1 inhibitor, has had a substantial impact on cancer treatment across multiple malignancies, but is associated with immune-related cardiovascular toxicities that pose significant clinical challenges. Complications such as myocarditis, arrhythmias, and cardiomyopathy are emerging as significant entities with high morbidity and mortality. This article is a narrative review and was not designed or conducted as a systematic review. No formal systematic review protocol was followed and attempts to identify or include all published studies on this topic were not undertaken. The goal is to provide a clinically oriented synthesis of the current literature on pembrolizumab-associated cardiotoxicity. A literature search was conducted using PubMed, Medline, and Google Scholar databases for articles published between January 2014 and March 2025. Search terms included ‘pembrolizumab,’ ‘PD-1 inhibitor,’ ‘immune checkpoint inhibitor,’ ‘cardiotoxicity,’ ‘myocarditis,’ ‘pericarditis,’ ‘arrhythmia,’ and ‘cardiac adverse events,’ used individually and in combination. Inclusion criteria encompassed English-language clinical trials, observational studies, systematic reviews, meta-analyses, pharmacovigilance analyses, clinical practice guidelines, and case reports involving human subjects. Non-English publications, preclinical studies without clinical correlates, and editorials without original data were excluded. Reference lists of identified articles were manually reviewed to identify additional relevant publications. Study selection was performed by a single author. Pembrolizumab-induced myocarditis, although rare, carries a high mortality rate and typically presents within the first few weeks of treatment, including a relative risk of myocarditis ~4.5 with combination immune checkpoint inhibitor therapy. Proposed mechanisms of this cardiotoxicity, though not settled, include shared antigenic targets between tumor and cardiac tissue and impaired immune tolerance. Current management relies on prompt recognition, immunosuppression with high-dose IV methylprednisolone as first-line therapy, and additional immunomodulatory agents for refractory cases. Emerging evidence from case reports and small cohort studies suggests potential benefit from abatacept with ruxolitinib in steroid-refractory cases; however, prospective validation is needed. Baseline cardiac screening and serial monitoring of cardiac biomarkers including high-sensitivity troponin and NT-proBNP, and a multidisciplinary cardio-oncology approach are essential for early detection and optimal outcomes.
DOI: https://doi.org/10.37349/ec.2026.1012117
Moderate ischemic mitral regurgitation (IMR) remains a ‘grey area’ for clinicians, with evidence-based decision-making for patients referred for coronary artery bypass grafting (CABG) being particularly challenging. IMR results from left ventricular remodeling and subvalvular deformation, not primary leaflet pathology. Even moderate regurgitation (effective regurgitant orifice area 20–39 mm2) is associated with a 1.5–2-fold increased risk of death. Among diagnostic methods, stress echocardiography is valuable but underutilized. An exercise-induced increase in the effective regurgitant orifice area of ≥ 13 mm2 or an absolute value ≥ 30 mm2 identifies patients with prognostically significant dynamic regurgitation requiring valve intervention, despite moderate resting values. Most randomized trials, particularly the Cardiothoracic Surgical Trials Network study, show that adding mitral valve annuloplasty to CABG reduces regurgitation severity but does not improve two-year survival or heart failure hospitalization rates, resulting in only a class IIb recommendation for the combined procedure. Modern imaging techniques, including three-dimensional echocardiography and cardiac magnetic resonance, provide added value in assessing IMR, annular geometry, and myocardial viability. Natriuretic peptides offer additional prognostic information. Transcatheter percutaneous mitral valve repair (‘edge-to-edge’) shows promise in high-risk patients and opens new prospects for hybrid revascularization. Optimal medical therapy, including Sacubitril/Valsartan and SGLT2 inhibitors, may slow IMR progression through enhanced reverse remodeling. In the absence of convincing evidence for any single approach, the current standard remains an individualized strategy implemented by the Heart Team, simultaneously considering clinical status, stress echocardiography data, anatomical characteristics, and surgical risks. Future research priorities include standardization of stress echocardiography protocols, validation of prognostic models, and long-term assessment of transcatheter approach outcomes in this complex patient category.
Moderate ischemic mitral regurgitation (IMR) remains a ‘grey area’ for clinicians, with evidence-based decision-making for patients referred for coronary artery bypass grafting (CABG) being particularly challenging. IMR results from left ventricular remodeling and subvalvular deformation, not primary leaflet pathology. Even moderate regurgitation (effective regurgitant orifice area 20–39 mm2) is associated with a 1.5–2-fold increased risk of death. Among diagnostic methods, stress echocardiography is valuable but underutilized. An exercise-induced increase in the effective regurgitant orifice area of ≥ 13 mm2 or an absolute value ≥ 30 mm2 identifies patients with prognostically significant dynamic regurgitation requiring valve intervention, despite moderate resting values. Most randomized trials, particularly the Cardiothoracic Surgical Trials Network study, show that adding mitral valve annuloplasty to CABG reduces regurgitation severity but does not improve two-year survival or heart failure hospitalization rates, resulting in only a class IIb recommendation for the combined procedure. Modern imaging techniques, including three-dimensional echocardiography and cardiac magnetic resonance, provide added value in assessing IMR, annular geometry, and myocardial viability. Natriuretic peptides offer additional prognostic information. Transcatheter percutaneous mitral valve repair (‘edge-to-edge’) shows promise in high-risk patients and opens new prospects for hybrid revascularization. Optimal medical therapy, including Sacubitril/Valsartan and SGLT2 inhibitors, may slow IMR progression through enhanced reverse remodeling. In the absence of convincing evidence for any single approach, the current standard remains an individualized strategy implemented by the Heart Team, simultaneously considering clinical status, stress echocardiography data, anatomical characteristics, and surgical risks. Future research priorities include standardization of stress echocardiography protocols, validation of prognostic models, and long-term assessment of transcatheter approach outcomes in this complex patient category.
DOI: https://doi.org/10.37349/ec.2026.1012116
Aim:
Takotsubo cardiomyopathy (TTC) is an acute form of systolic dysfunction triggered by physical or emotional stress, most commonly seen in postmenopausal women. Its pathophysiology involves catecholamine surge, autonomic imbalance, and microvascular dysfunction. Fibromyalgia is a chronic pain disorder observed primarily in premenopausal women characterized by autonomic dysregulation, central sensitization, and high psychiatric comorbidity—mechanisms that overlap substantially with TTC. Nevertheless, fibromyalgia has not been established as an independent risk factor for TTC. This study evaluated the association between fibromyalgia and TTC using a nationally representative sample.
Methods:
A retrospective case-control study was conducted using the 2022 National Inpatient Sample. Adult hospitalizations with TTC (ICD-10-CM I51.81) were identified, and a 1% random sample of non-TTC admissions served as controls. Fibromyalgia was defined by ICD-10 code M79.7. Survey-weighted multivariable logistic regression assessed the association between fibromyalgia and TTC, adjusting for demographics, comorbidities, and severity of illness.
Results:
Among 9,376 TTC and 65,690 control hospitalizations, fibromyalgia was present in 282 (3.0%) TTC cases and 827 (1.3%) controls. After multivariable adjustment, fibromyalgia was independently associated with TTC (OR 1.19; 95% CI 1.00–1.42, P = 0.044). This association persisted after accounting for psychiatric comorbidities.
Conclusions:
Fibromyalgia was associated with increased odds of TTC. These findings highlight the need for vigilance in evaluating fibromyalgia patients with chest pain and warrant further research into mechanisms underlying stress-induced cardiomyopathy.
Aim:
Takotsubo cardiomyopathy (TTC) is an acute form of systolic dysfunction triggered by physical or emotional stress, most commonly seen in postmenopausal women. Its pathophysiology involves catecholamine surge, autonomic imbalance, and microvascular dysfunction. Fibromyalgia is a chronic pain disorder observed primarily in premenopausal women characterized by autonomic dysregulation, central sensitization, and high psychiatric comorbidity—mechanisms that overlap substantially with TTC. Nevertheless, fibromyalgia has not been established as an independent risk factor for TTC. This study evaluated the association between fibromyalgia and TTC using a nationally representative sample.
Methods:
A retrospective case-control study was conducted using the 2022 National Inpatient Sample. Adult hospitalizations with TTC (ICD-10-CM I51.81) were identified, and a 1% random sample of non-TTC admissions served as controls. Fibromyalgia was defined by ICD-10 code M79.7. Survey-weighted multivariable logistic regression assessed the association between fibromyalgia and TTC, adjusting for demographics, comorbidities, and severity of illness.
Results:
Among 9,376 TTC and 65,690 control hospitalizations, fibromyalgia was present in 282 (3.0%) TTC cases and 827 (1.3%) controls. After multivariable adjustment, fibromyalgia was independently associated with TTC (OR 1.19; 95% CI 1.00–1.42, P = 0.044). This association persisted after accounting for psychiatric comorbidities.
Conclusions:
Fibromyalgia was associated with increased odds of TTC. These findings highlight the need for vigilance in evaluating fibromyalgia patients with chest pain and warrant further research into mechanisms underlying stress-induced cardiomyopathy.
DOI: https://doi.org/10.37349/ec.2026.1012115
This article belongs to the special issue Heart–Brain Interactions: Clinical-Psychological Perspectives on Cardiovascular Function
Aim:
Artificial intelligence may support syncope evaluation, but reliability of language models in structured syncope care remains uncertain. We evaluated diagnostic performance, safety, and within-case consistency of Generative Pre-trained Transformer-5 (GPT-5) in patients with transient loss of consciousness (T-LOC).
Methods:
This prospective cohort study included 55 patients evaluated in syncope units. GPT-5 and a syncope-expert assessed identical case information after core evaluation (CE: history-taking, physical examination, active standing test, and 12-lead electrocardiogram) and extended evaluation (EE: CE plus additional testing when indicated). An expert panel adjudicated the final diagnosis after 18 months. Outcomes were diagnostic yield, final-diagnosis inclusion rate, diagnostic precision score (DPS), cardiac diagnostic safety, and within-case consistency across five repeated GPT-5 runs.
Results:
Of 55 patients, 54 had complete follow-up for performance analyses. Diagnostic yield was 94% for the syncope-expert at CE and EE, and 100% and 96% for GPT-5 at CE and EE, respectively. GPT-5 included the final diagnosis in 52% (CE) and 57% (EE) of cases, versus 67% for the syncope-expert. DPS remained negative for GPT-5 at CE (mean −0.03, SD 0.54) and EE (mean −0.01, SD 0.49). Among four final cardiac syncope cases, GPT-5 selected the final diagnosis in one case and the syncope-expert in three. First-diagnosis consistency across five GPT-5 runs was 69% after CE and 74% after EE.
Conclusions:
GPT-5 generated diagnostic outputs frequently but showed limited precision, cardiac safety concerns, and within-case variability. Its role in syncope evaluation should remain supportive within clinician-led pathways rather than autonomous.
Aim:
Artificial intelligence may support syncope evaluation, but reliability of language models in structured syncope care remains uncertain. We evaluated diagnostic performance, safety, and within-case consistency of Generative Pre-trained Transformer-5 (GPT-5) in patients with transient loss of consciousness (T-LOC).
Methods:
This prospective cohort study included 55 patients evaluated in syncope units. GPT-5 and a syncope-expert assessed identical case information after core evaluation (CE: history-taking, physical examination, active standing test, and 12-lead electrocardiogram) and extended evaluation (EE: CE plus additional testing when indicated). An expert panel adjudicated the final diagnosis after 18 months. Outcomes were diagnostic yield, final-diagnosis inclusion rate, diagnostic precision score (DPS), cardiac diagnostic safety, and within-case consistency across five repeated GPT-5 runs.
Results:
Of 55 patients, 54 had complete follow-up for performance analyses. Diagnostic yield was 94% for the syncope-expert at CE and EE, and 100% and 96% for GPT-5 at CE and EE, respectively. GPT-5 included the final diagnosis in 52% (CE) and 57% (EE) of cases, versus 67% for the syncope-expert. DPS remained negative for GPT-5 at CE (mean −0.03, SD 0.54) and EE (mean −0.01, SD 0.49). Among four final cardiac syncope cases, GPT-5 selected the final diagnosis in one case and the syncope-expert in three. First-diagnosis consistency across five GPT-5 runs was 69% after CE and 74% after EE.
Conclusions:
GPT-5 generated diagnostic outputs frequently but showed limited precision, cardiac safety concerns, and within-case variability. Its role in syncope evaluation should remain supportive within clinician-led pathways rather than autonomous.
DOI: https://doi.org/10.37349/ec.2026.1012114
Sodium–glucose cotransporter 2 inhibitors (SGLT2i) were originally developed as glucose-lowering therapies for type 2 diabetes mellitus. However, robust clinical evidence has demonstrated substantial cardiovascular and renal protective effects that extend beyond glycemic control. Emerging data highlight their systemic influence across the cardiovascular–renal–metabolic (CRM) continuum, a conceptual framework describing the shared pathophysiological links between metabolic dysfunction, heart failure (HF), and chronic kidney disease (CKD). Despite the rapid expansion of clinical and mechanistic evidence, the integration of these insights into coordinated therapeutic implementation across cardiology, nephrology, and endocrinology remains incompletely synthesized. This structured narrative review synthesized evidence from PubMed/MEDLINE, Embase, and Google Scholar to identify relevant studies published between January 2016 and December 2025. Emphasis was placed on randomized controlled trials, meta-analyses, large observational cohorts, guideline documents, and translational mechanistic investigations evaluating pharmacologic mechanisms, clinical efficacy, and multidisciplinary applications of SGLT2i across CRM conditions. Cardiovascular and renal outcome trials consistently show that SGLT2i reduce hospitalization for heart failure, delay CKD progression, and improve major cardiovascular outcomes in both diabetic and non-diabetic populations. Mechanistically, these agents restore tubuloglomerular feedback, enhance cardiac energy efficiency through increased ketone utilization, attenuate inflammatory and profibrotic signaling pathways, and improve mitochondrial bioenergetics. These multisystem effects contribute to therapeutic benefits across HF phenotypes and CKD stages while also improving metabolic parameters such as adiposity, blood pressure, and hepatic steatosis. Collectively, current evidence supports SGLT2i as foundational disease-modifying therapies across the CRM spectrum. Future investigations should prioritize precision-based treatment approaches, biomarker-guided patient selection, and rational combination pharmacotherapy to further optimize outcomes across interconnected cardiovascular, renal, and metabolic diseases.
Sodium–glucose cotransporter 2 inhibitors (SGLT2i) were originally developed as glucose-lowering therapies for type 2 diabetes mellitus. However, robust clinical evidence has demonstrated substantial cardiovascular and renal protective effects that extend beyond glycemic control. Emerging data highlight their systemic influence across the cardiovascular–renal–metabolic (CRM) continuum, a conceptual framework describing the shared pathophysiological links between metabolic dysfunction, heart failure (HF), and chronic kidney disease (CKD). Despite the rapid expansion of clinical and mechanistic evidence, the integration of these insights into coordinated therapeutic implementation across cardiology, nephrology, and endocrinology remains incompletely synthesized. This structured narrative review synthesized evidence from PubMed/MEDLINE, Embase, and Google Scholar to identify relevant studies published between January 2016 and December 2025. Emphasis was placed on randomized controlled trials, meta-analyses, large observational cohorts, guideline documents, and translational mechanistic investigations evaluating pharmacologic mechanisms, clinical efficacy, and multidisciplinary applications of SGLT2i across CRM conditions. Cardiovascular and renal outcome trials consistently show that SGLT2i reduce hospitalization for heart failure, delay CKD progression, and improve major cardiovascular outcomes in both diabetic and non-diabetic populations. Mechanistically, these agents restore tubuloglomerular feedback, enhance cardiac energy efficiency through increased ketone utilization, attenuate inflammatory and profibrotic signaling pathways, and improve mitochondrial bioenergetics. These multisystem effects contribute to therapeutic benefits across HF phenotypes and CKD stages while also improving metabolic parameters such as adiposity, blood pressure, and hepatic steatosis. Collectively, current evidence supports SGLT2i as foundational disease-modifying therapies across the CRM spectrum. Future investigations should prioritize precision-based treatment approaches, biomarker-guided patient selection, and rational combination pharmacotherapy to further optimize outcomes across interconnected cardiovascular, renal, and metabolic diseases.
DOI: https://doi.org/10.37349/ec.2026.1012113
Gasdermin D (GSDMD) has been identified as a potential key effector protein within the inflammatory response and is characterized as a primary executor of pyroptosis through the formation of transmembrane pores. This review evaluates the emerging role of GSDMD-mediated pyroptosis in the pathogenesis of cardiovascular diseases (CVDs), with a specific focus on its potential contributions to atherosclerosis. We examine how the activation of GSDMD by inflammasomes, such as NLRP3 and AIM2, facilitates the release of inflammatory cytokines (IL-1β and IL-18) and damage-associated molecular patterns (DAMPs). Central to this discussion is the proposed role of GSDMD in driving macrophage foam cell death and vascular smooth muscle cell (VSMC) dysfunction. These factors are associated with necrotic core expansion and increased risk of atherosclerotic plaque instability. Furthermore, GSDMD may mediate endothelial dysfunction and disrupt lipid metabolism, and is suggested to participate in systemic signaling via extracellular vesicles. Finally, we highlight the therapeutic potential of targeting GSDMD as a possible strategy to stabilize vulnerable plaques, which may offer new avenues for cardiovascular precision medicine.
Gasdermin D (GSDMD) has been identified as a potential key effector protein within the inflammatory response and is characterized as a primary executor of pyroptosis through the formation of transmembrane pores. This review evaluates the emerging role of GSDMD-mediated pyroptosis in the pathogenesis of cardiovascular diseases (CVDs), with a specific focus on its potential contributions to atherosclerosis. We examine how the activation of GSDMD by inflammasomes, such as NLRP3 and AIM2, facilitates the release of inflammatory cytokines (IL-1β and IL-18) and damage-associated molecular patterns (DAMPs). Central to this discussion is the proposed role of GSDMD in driving macrophage foam cell death and vascular smooth muscle cell (VSMC) dysfunction. These factors are associated with necrotic core expansion and increased risk of atherosclerotic plaque instability. Furthermore, GSDMD may mediate endothelial dysfunction and disrupt lipid metabolism, and is suggested to participate in systemic signaling via extracellular vesicles. Finally, we highlight the therapeutic potential of targeting GSDMD as a possible strategy to stabilize vulnerable plaques, which may offer new avenues for cardiovascular precision medicine.
DOI: https://doi.org/10.37349/ec.2026.1012112
Aim:
Low cardiac output syndrome (LCOS) may be improvable; hence, timely detection and intervention are essential. However, no model has been established for the prediction of LCOS onset post non-isolated coronary artery bypass grafting (CABG) surgery. Therefore, this study aimed to develop a machine-learning-based model to predict LCOS after non-isolated CABG.
Methods:
A total of 378 patients who underwent non-isolated CABG at Nanjing First Hospital, China, were retrospectively assessed. Five algorithms [L2 regularized logistic regression (LR), random forest (RF) classifier, extreme gradient boosting (XGB), light gradient boosting machine (LGBM), and support vector machine (SVM)] were employed. Model performance and clinical utility were evaluated using area under the curve (AUC), 10-fold cross-validation, and decision curve analysis (DCA). SHapley Additive exPlanations (SHAP) were used to assess the model’s interpretability. A web calculator was developed.
Results:
XGB showed superior performance and calibration (AUC: 0.933, 95% CI: 0.903–0.962; Brier score of 0.107), with excellent specificity (0.865), accuracy (0.860), and precision (0.753). In testing, XGB maintained excellent discrimination (AUC: 0.868, 95% CI: 0.799–0.936), best specificity (0.785), accuracy (0.781), and precision (0.614). DCA confirmed clinical usefulness. SHAP analysis identified the ejection fraction, left ventricular end-systolic diameter, and lactate levels as the most influential predictors. The web calculator is accessible via https://lcos-cabg-xgb-model.streamlit.app/
Conclusions:
The developed web-based XGB model effectively predicts LCOS after non-isolated CABG, aiding early risk stratification and detection.
Aim:
Low cardiac output syndrome (LCOS) may be improvable; hence, timely detection and intervention are essential. However, no model has been established for the prediction of LCOS onset post non-isolated coronary artery bypass grafting (CABG) surgery. Therefore, this study aimed to develop a machine-learning-based model to predict LCOS after non-isolated CABG.
Methods:
A total of 378 patients who underwent non-isolated CABG at Nanjing First Hospital, China, were retrospectively assessed. Five algorithms [L2 regularized logistic regression (LR), random forest (RF) classifier, extreme gradient boosting (XGB), light gradient boosting machine (LGBM), and support vector machine (SVM)] were employed. Model performance and clinical utility were evaluated using area under the curve (AUC), 10-fold cross-validation, and decision curve analysis (DCA). SHapley Additive exPlanations (SHAP) were used to assess the model’s interpretability. A web calculator was developed.
Results:
XGB showed superior performance and calibration (AUC: 0.933, 95% CI: 0.903–0.962; Brier score of 0.107), with excellent specificity (0.865), accuracy (0.860), and precision (0.753). In testing, XGB maintained excellent discrimination (AUC: 0.868, 95% CI: 0.799–0.936), best specificity (0.785), accuracy (0.781), and precision (0.614). DCA confirmed clinical usefulness. SHAP analysis identified the ejection fraction, left ventricular end-systolic diameter, and lactate levels as the most influential predictors. The web calculator is accessible via https://lcos-cabg-xgb-model.streamlit.app/
Conclusions:
The developed web-based XGB model effectively predicts LCOS after non-isolated CABG, aiding early risk stratification and detection.
DOI: https://doi.org/10.37349/ec.2026.1012111
Aim:
Older adults with dyslipidemia often have coexisting diabetes and hypertension, requiring triple therapy with statins, antihypertensives, and oral antidiabetics. Given that statin adherence is a key metric in the Medicare STAR Ratings program, understanding statin use in this population is critical. However, prior studies have focused on adherence to statin monotherapy or composite adherence to triple therapy, with limited evidence on statin-specific patterns in this population.
Methods:
We conducted a retrospective cohort study using a Texas-based Medicare Advantage database (2016–2017). Adults receiving concurrent triple therapy (statins, renin-angiotensin system antagonists, and oral antidiabetics) were followed for 12 months. Statin adherence was measured monthly using the proportion of days covered (PDC) and modeled using group-based trajectory modeling (GBTM). Multinomial logistic regression, informed by the Andersen behavioral model, was used to identify sociodemographic and clinical predictors of adherence trajectories.
Results:
Among 7,847 patients, three distinct statin adherence trajectories were identified: near-perfect adherence (57.0%), adherent (23.6%), and rapid decline (19.4%). Female sex was associated with higher odds of rapid decline than male sex. Younger age (≤ 65 years) and having at least one prior hospitalization were significant predictors of rapid adherence decline, whereas older age and a greater number of concomitant medications were associated with lower odds of decline. Notably, about 80% of patients were adherent to statin despite lower adherence to the overall triple-therapy regimen.
Conclusions:
This study identified three distinct statin adherence trajectories among older adults on triple therapy. By highlighting predictors of rapid adherence decline, including female sex and prior hospitalization, these findings can help clinicians identify high-risk patients and inform targeted interventions to improve adherence and cardiovascular outcomes.
Aim:
Older adults with dyslipidemia often have coexisting diabetes and hypertension, requiring triple therapy with statins, antihypertensives, and oral antidiabetics. Given that statin adherence is a key metric in the Medicare STAR Ratings program, understanding statin use in this population is critical. However, prior studies have focused on adherence to statin monotherapy or composite adherence to triple therapy, with limited evidence on statin-specific patterns in this population.
Methods:
We conducted a retrospective cohort study using a Texas-based Medicare Advantage database (2016–2017). Adults receiving concurrent triple therapy (statins, renin-angiotensin system antagonists, and oral antidiabetics) were followed for 12 months. Statin adherence was measured monthly using the proportion of days covered (PDC) and modeled using group-based trajectory modeling (GBTM). Multinomial logistic regression, informed by the Andersen behavioral model, was used to identify sociodemographic and clinical predictors of adherence trajectories.
Results:
Among 7,847 patients, three distinct statin adherence trajectories were identified: near-perfect adherence (57.0%), adherent (23.6%), and rapid decline (19.4%). Female sex was associated with higher odds of rapid decline than male sex. Younger age (≤ 65 years) and having at least one prior hospitalization were significant predictors of rapid adherence decline, whereas older age and a greater number of concomitant medications were associated with lower odds of decline. Notably, about 80% of patients were adherent to statin despite lower adherence to the overall triple-therapy regimen.
Conclusions:
This study identified three distinct statin adherence trajectories among older adults on triple therapy. By highlighting predictors of rapid adherence decline, including female sex and prior hospitalization, these findings can help clinicians identify high-risk patients and inform targeted interventions to improve adherence and cardiovascular outcomes.
DOI: https://doi.org/10.37349/ec.2026.1012110
Cardiovascular disease (CVD) is the leading cause of mortality in women worldwide. While increasing parity has been associated with greater CVD risk in several populations, limited data exist on this association in South Asian women who experience some of the highest fertility rates globally. This narrative review synthesizes current literature examining the relationship between multiparity and CVD in South Asian women, including epidemiologic patterns, proposed biological mechanisms, and the influence of sociocultural factors. Evidence from South Asia suggests a possible association between high parity (particularly ≥ 4 or 5 births) and increased risk of hypertension, obesity, metabolic syndrome, and coronary heart disease. However, the available data are limited, largely cross-sectional, and occasionally contradictory. Some studies found no association or even protective effects at lower parity levels, suggesting a potential threshold or nonlinear effect. Biologically, proposed mechanisms include insulin resistance, endothelial dysfunction, and dysregulation of adipokines. Sociocultural factors such as male child preference, restricted contraceptive access, and limited autonomy in family planning decisions may also contribute to high parity and indirectly affect cardiovascular health. Although global research supports a positive association between multiparity and CVD, the evidence specific to South Asian populations remains inconsistent and underexplored. Further region-specific, longitudinal research is essential to clarify causality and inform culturally tailored screening and prevention strategies.
Cardiovascular disease (CVD) is the leading cause of mortality in women worldwide. While increasing parity has been associated with greater CVD risk in several populations, limited data exist on this association in South Asian women who experience some of the highest fertility rates globally. This narrative review synthesizes current literature examining the relationship between multiparity and CVD in South Asian women, including epidemiologic patterns, proposed biological mechanisms, and the influence of sociocultural factors. Evidence from South Asia suggests a possible association between high parity (particularly ≥ 4 or 5 births) and increased risk of hypertension, obesity, metabolic syndrome, and coronary heart disease. However, the available data are limited, largely cross-sectional, and occasionally contradictory. Some studies found no association or even protective effects at lower parity levels, suggesting a potential threshold or nonlinear effect. Biologically, proposed mechanisms include insulin resistance, endothelial dysfunction, and dysregulation of adipokines. Sociocultural factors such as male child preference, restricted contraceptive access, and limited autonomy in family planning decisions may also contribute to high parity and indirectly affect cardiovascular health. Although global research supports a positive association between multiparity and CVD, the evidence specific to South Asian populations remains inconsistent and underexplored. Further region-specific, longitudinal research is essential to clarify causality and inform culturally tailored screening and prevention strategies.
DOI: https://doi.org/10.37349/ec.2026.1012108
This article belongs to the special issue Cardiovascular Risk for Mothers and Offspring Resulting from Complicated Pregnancy
