INTRODUCTION:Conduction System Pacing (CSP) is a physiologic alternative to right ventricular pacing and may be advantageous in Cardiac Amyloidosis (CA), where conduction disease and septal infiltration are common. METHODS:A systematic review of 9 published studies, including 7 case reports or small series and 2 retrospective cohorts, identified 59 patients with CA who underwent CSP. RESULTS:Left bundle branch area pacing was the predominant technique. Implant success was high overall, ranging between 80 and 95%, with acute capture thresholds between 0.5 and 1.0 V at 0.5 ms and stable performance during follow-up. Paced QRS duration was typically 120-140 ms, representing QRS narrowing in most patients. In individual cases, improvement in New York Heart Association class, natriuretic peptide levels, and left ventricular ejection fraction was observed; however, cohort data demonstrated stable systolic function (45.5% to 41.9%) and unchanged NT-proBNP concentrations. Heart failure hospitalization occurred in 17-35% of patients, and mortality was limited to disease progression in AL amyloidosis. No device-related complications were reported. DISCUSSION:CSP in cardiac amyloidosis appears technically feasible and electrically stable in CA and may mitigate the deleterious effects of chronic right ventricular pacing. However, reproducible and longitudinal clinical benefit has not been demonstrated. CONCLUSION:Conduction system pacing in cardiac amyloidosis is feasible with favourable electrical parameters, but its clinical utility remains uncertain. Larger prospective registries are required to define its role relative to conventional biventricular pacing.
INTRODUCTION:The use of cardiovascular magnetic resonance (CMR) T1 mapping is becoming the dominant method for quantitatively characterizing diffuse tissue abnormalities in the myocardium that cannot be detected by traditional late gadolinium enhancement (LGE). This review provides a comprehensive overview of recent technical advances in T1 mapping, including a critical evaluation of the different acquisition techniques and their clinical applications. It also examines the role of artificial intelligence (AI) in the interpretation of T1 mapping data. It discusses its potential impact on clinical implementation and the translation of T1 mapping into routine practice. METHODS:A narrative review of the current literature related to T1 mapping was conducted using PubMed and Scopus. The search focused on T1 mapping techniques, including their development, normal ranges, clinical applications, and AI approaches to T1 mapping image analysis. RESULTS:Differentiation among T1 mapping techniques (MOLLI, SHMOLLI, SASHA, SMART1Map) based on accuracy, robustness, and acquisition limitations can influence their use in clinical practice. The literature indicates considerable variability in the T1 normal range, which is attributed to sequence type, magnetic field strength, manufacturer, and patient characteristics, making it challenging to create a universal reference range. From a clinical perspective, T1 mapping helps evaluate cardiomyopathy, infiltrative and ischemic disease (including myocarditis), as it shows improved ability to detect diffuse myocardial involvement compared to LGE alone. AI algorithms may be useful for automating segmentation, reducing motion artefacts, and improving measurement consistency. DISCUSSION:Despite its considerable clinical value, the broader implementation of T1 mapping remains challenged by variations in acquisition protocols and the lack of universally standardized reference values. Artificial intelligence may help mitigate some of these limitations by enhancing measurement consistency and facilitating automated image analysis. Nevertheless, further validation studies and greater harmonization across imaging platforms are still necessary before AI-driven approaches can be fully integrated into routine clinical practice. CONCLUSION:T1 mapping represents a valuable non-invasive technique for myocardial tissue characterization. Although AI has the potential to enhance reproducibility, improve image quality, and streamline workflow, broader clinical adoption remains contingent upon further efforts. These include the standardization of acquisition and analysis methods, validation in large multicenter cohorts, and the attainment of regulatory approval.
Failure of tricuspid valve prostheses is an increasingly encountered and complex clinical problem. Patients often present with advanced comorbidities, progressive right ventricular dysfunction, and prohibitive surgical risk. Despite growing burden, high-quality evidence and clear guideline-directed strategies remain limited. This narrative review summarizes contemporary approaches to the management of failed tricuspid valve prostheses, which include traditional redosurgical re-intervention, minimal invasive and beating-heart surgical techniques, and transcatheter valve-in-valve and valve-in-ring implantation, as well as emerging therapies for failed transcatheter tricuspid devices. Redo tricuspid valve surgery has historically carried substantial perioperative risk, although outcomes have improved at experienced centers, particularly with less invasive surgical approaches. Transcatheter valve-in-valve and valve-in-ring procedures demonstrate a high procedural success rate and favorable early outcomes in selected patient profiles with failed bioprosthetic valves or annuloplasty rings. However, durability beyond short to mid-term remains uncertain, especially in younger individuals. Given the heterogeneity of the prosthesis types and patients' profiles, the management should be individualized. A multidisciplinary Heart Team approach that integrates surgical risk, right ventricular function, prosthesis characteristics, and anatomic considerations is essential to optimize outcomes in this high-risk patient population. Given the limited and heterogeneous nature of currently available evidence, this review was designed as a clinically focused narrative review rather than a formal systematic review or meta-analysis.
INTRODUCTION:To synthesize contemporary evidence on epidemiology, triggers and risk factors, pathophysiology, clinical presentation, diagnosis, management patterns, and outcomes in Takotsubo Syndrome (TTS) restricted to studies using the International Takotsubo (InterTAK) Diagnostic Criteria. METHODS:A PRISMA‑guided systematic review of major bibliographic databases was performed, limited to studies published between 2019 and October 2024. Pre‑specified criteria were: Inter- TAK diagnosis, English language, and minimum sample size ≥ 30. No meta‑analysis was initially planned due to heterogeneity; however, to report more precisely on in-hospital mortality, we focused on a minimal meta-analysis based on high-quality publications. RESULTS:Across studies, approximately 78% of participants were female, with reported mean ages ranging from 54 to 79 years. Physical triggers were most frequent and associated with higher rates of cardiogenic shock and mortality. Emotional triggers had the most favourable short-term outcomes, while unknown-trigger cases more often presented with arrhythmia. T-wave inversion and ST-segment changes were the most common Electrocardiogram (ECG) findings. Several noninvasive diagnostic tools showed high accuracy in differentiating TTS from ACS. Management was largely supportive and heart-failure/ACS-oriented. In-hospital mortality ranged from 5% in general cardiology series to > 60% in ICU cohorts. Early ventricular arrhythmias occurred predominantly within 48 hours and were predicted by QTc. Long-term follow-up revealed variable mortality rates but frequent persistent subclinical dysfunction despite recovery of Left Ventricular Ejection Fraction (LVEF). Persistent Left Ventricular Global Longitudinal Strain (LV-GLS) impairment at 3-6 months was associated with adverse long-term outcomes. DISCUSSION:This review exclusively focused on studies applying the InterTAK Diagnostic Criteria. A major strength of this review is its diagnostic consistency. The epidemiological profile of TTS in the included studies closely aligns with prior large-scale registry data, particularly the InterTAK Registry (2), which demonstrated a predominance among postmenopausal women and a mean presentation age in the late sixties. This diversity in presentation underscores the importance of early, structured assessment whenever TTS is suspected. Bedside clinical scores may improve early triage of suspected TTS, particularly when angiography is delayed or inconclusive. CONCLUSION:TTS is a heterogeneous condition with diverse presentations, evolving diagnostic tools, and important prognostic implications. Large, prospective studies are needed to refine diagnosis, validate prognostic tools, and develop effective targeted therapies to improve outcomes.
Introduction: Heart transplantation is a life-saving procedure with well-documented physiological outcomes. However, its psychosocial implications, particularly personality changes, remain underexplored. This study aims to explore post-transplant personality changes in heart recipients and possible contributing factors. Methods: 19 heart transplant recipients were interviewed via semi-structured video calls. Interviews focused on changes in personality traits, emotions, preferences, spirituality, and selfawareness. Thematic analysis and quantitative coding were used to identify recurring patterns. Statistical tests were applied to evaluate potential correlations with donor-recipient variables. Results: 17 of 19 recipients reported at least one personality change. Common themes included increased empathy, altered food preferences, aversion to meat, heightened spirituality, and greater motivation. Female recipients and those with a donor of the opposite gender or a >10-year age gap experienced more changes on average. The age gap effect was statistically significant (p = 0.00098). Emotional changes were the most frequently reported domain. Discussion: This study highlights the prevalence and complexity of personality changes following heart transplantation. These findings suggest that heart transplants may influence recipient identity beyond physiological recovery. Conclusion: These findings are exploratory and intended to generate hypotheses for future controlled studies. Greater awareness of this phenomenon can improve post-transplant care and patient well-being.
INTRODUCTION:Cardiovascular diseases remain the leading cause of mortality worldwide. Emerging risk factors, such as electronic cigarettes and Heated Tobacco Products (HTPs), may contribute to vascular damage. This systematic review and meta-analysis aimed to evaluate the association between nicotine-containing electronic cigarettes and HTPs and arterial stiffness. METHODS:The study followed PRISMA and Cochrane Collaboration guidelines and was registered in the PROSPERO database (ID: CRD42023446895). PubMed, Scopus, Google Scholar, and eLIBRARY databases from January 1, 2000 to July 30, 2024. Outcomes included Pulse Wave Velocity (PWV), Augmentation Index (AIx), Cardio-Ankle Vascular Index (CAVI), ankle- brachial index (ABI). RESULTS:From 3,705 abstracts, 9 experimental studies (n=190) were included. CAVI and ABI indices were excluded due to limited data. The PWV analysis included 6 studies (n=133) and demonstrated a significant increase following exposure to nicotine-containing products (SMD=1.71 [95% CI: 0.23-3.19, p=0.031]). The AIx analysis included 9 studies (n=190) and also demonstrated a significant increase (SMD=1.05 [95% CI: 0.34-1.76, p=0.008]). Metaregression analyses showed no significant moderating effects of publication year, age, or sex. However, small-study effects and substantial heterogeneity were identified. DISCUSSION:The study's findings are consistent with previous studies and suggest possible vascular effects of nicotine-containing electronic cigarettes and HTPs. However, limitations require cautious interpretation, and long-term studies are warranted. CONCLUSION:Evidence suggests a possible acute increase in arterial stiffness following exposure to nicotine-containing electronic cigarettes and HTPs compared with non-smokers or nicotinefree electronic cigarette users, but certainty is limited by high heterogeneity, small samples, and methodological variability.
INTRODUCTION:Bicuspid Aortic Valve (BAV) is the most common congenital heart disease and often causes aortic stenosis in younger adults. There are few prospective randomized trials comparing Transcatheter Aortic Valve Replacement (TAVR) and Surgical Aortic Valve Replacement (SAVR) in BAV patients, since these patients are usually excluded from major studies because of their complex anatomy. A meta-analysis to compare clinical outcomes between TAVR and SAVR in people with BAV was conducted. METHODS:PubMed, Google Scholar, and SCOPUS were searched for studies published up to December 2023 that compared TAVR and SAVR in patients with BAV. The main outcomes that were examined were mortality, atrial fibrillation, permanent pacemaker implantation, stroke, respiratory complications, and acute kidney injury. Forward and backward citation searches were also used. Random-effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals, and heterogeneity was assessed using the I² statistic. Sensitivity analyses were performed by removing one study at a time. RESULTS:The analysis included seven studies with a total of 96,430 BAV patients. Of these, 41,110 had TAVR and 55,320 had SAVR. Patients who had TAVR were less likely to experience in-hospital respiratory complications, bleeding or need for transfusion, and new-onset atrial fibrillation. However, they were more likely to need a permanent pacemaker. There were no significant differences between the groups in short-term mortality, stroke, or acute kidney injury. DISCUSSION:Lower peri-procedural morbidity with TAVR likely reflects its minimally invasive nature, whereas higher pacemaker rates may relate to bicuspid valve anatomy and conduction system vulnerability. CONCLUSION:TAVR appears to be a reasonable alternative to SAVR in carefully selected BAV patients, but randomized trials and long-term follow-up remain necessary.
INTRODUCTION:Levosimendan is a calcium-sensitizing inotropic agent recommended for Heart Failure (HF) treatment but contraindicated in patients with Creatinine Clearance (Ccr) below 30 mL/min. This study aims to systematically evaluate its efficacy and safety in patients with severe renal insufficiency. METHODS:A systematic literature search was conducted in PubMed, Embase, and the Cochrane Library. Randomized Controlled Trials (RCTs) and cohort studies comparing the efficacy and safety of levosimendan in patients with severe renal insufficiency were included. Studies reporting outcomes only in patients with normal renal function or those with Ccr greater than 30 mL/min were excluded. The primary outcome was all-cause mortality. RESULTS:A total of 1541 records were identified, and seven studies enrolling 814 patients were included in the meta-analysis. There was no significant difference in all-cause mortality between levosimendan and control groups [odds ratio (OR) 1.13, 95% confidence interval (CI) 0.66 to 1.94, p = 0.67, I2 = 23%]. Subgroup analyses showed no significant differences in 30-day mortality [OR 1.17, 95% CI (0.69, 1.99), p = 0.55, I2 = 15%] or 180-day mortality [OR 1.09, 95% CI (0.39, 13.06), p = 0.87, I2 = 57%]. DISCUSSION:The absence of mortality benefit may reflect levosimendan's altered pharmacokinetics and competing uremic risks in severe renal insufficiency. However, renoprotective mechanisms have been primarily characterized in populations without renal impairment, and the prolonged half-life of OR-1896 in this setting may potentiate both hemodynamic effects and adverse events. CONCLUSION:This study found that available evidence from small, heterogeneous observational studies is insufficient to determine whether levosimendan affects mortality in severe renal insufficiency. These findings do not support any clinical recommendation, provide no basis to modify the existing contraindication for Ccr below 30 mL/min, and highlight the need for further RCTs with comprehensive endpoints.
INTRODUCTION:Understanding the relationship between health beliefs and other variables, such as physical and mental fatigue, is extremely important for the implementation of a patient-centered therapeutic approach. The main purpose of this study was to investigate the physical and mental fatigue and health beliefs of patients with cardiorespiratory problems. METHODOLOGY:The sample consisted of 100 patients with cardiorespiratory problems, and the research was conducted at the General Hospital of Argolis, using a questionnaire. The distribution of the questionnaires took place during the period October 2024 - November 2024, and the statistical analysis was performed with the SPSSv24 program. RESULTS:On average, patients with cardiorespiratory problems who participated in this study presented moderate levels of physical fatigue, very low levels of mental fatigue, fairly high levels of internal health control, low levels of attribution of health control to chance, extremely high levels of attribution of health control to physicians, and moderate levels of attribution of health control to significant others. Various demographic characteristics, such as age, educational level, type of employment, and length of time of treatment of various cardiorespiratory problems, but not the type and number of cardiorespiratory problems, seemed to have a significant effect. DISCUSSION:Physical, mental, and overall fatigue were significantly and negatively correlated with internal control, attributing health control to chance, and attributing health control to physicians. CONCLUSION:Sociodemographic and clinical factors are associated with fatigue and health locus of control in Greek patients suffering from cardiorespiratory problems.
Introduction: The study aims to assess clinical, laboratory, and instrumental outcomes depending on smoking status in patients undergoing Cardiac Rehabilitation (CR) after Acute Coronary Syndrome (ACS). Methods: The prospective cohort study involved 124 post-ACS patients (aged 28-77 years; Me = 57, IQR: 48-64). Data collection occurred at three stages: during inpatient CR, after 3-6 months, and one year post-ACS. Patients underwent clinical evaluation, smoking status assessment, laboratory tests (complete blood count, lipid profile, PCSK9 levels), and instrumental studies (echocardiography, bicycle ergometry, coronary angiography). Results: The proportion of smokers decreased by 47.6 ± 10.8% after one year of CR. Smoking patients had significantly higher ESV values [70.0 (61.2,84.0) mL] than non-smokers [52.5 (45.3,61.3) mL] (p = .003). Patients who quit smoking showed no significant difference in ESV or ESVI compared to non-smokers at 3-6 months, suggesting stabilization of remodeling. Nonsmokers and quitters had favorable lipid dynamics: PCSK9 levels decreased after physical exertion (512.0 to 467.5 ng/mL; p = .001) and remained lower throughout the year (p = .036). At one year, total cholesterol was lower in quitters, 3.80 (3.35,4.10) mmol/L, than in smokers, 4.60 (3.73,5.68) mmol/L, p = .03; LDL-C was also lower in quitters, 2.07 (1.55,2.73) mmol/L vs. smokers, 2.71 (2.13,3.96) mmol/L, p = .02. Discussion: These findings may suggest that smoking status could influence recovery patterns after ACS during СR. Conclusion: In this observational cohort, both smoking cessation during cardiac rehabilitation and the absence of smoking tended to be associated with more favorable echocardiographic parameters and lipid profile, including lower levels of total cholesterol, LDL-C, and PCSK9, in patients after ACS.
Introduction: The American Heart Association recognizes the interrelated burden of obesity, type 2 Diabetes Mellitus (DM), Cardiovascular Disease (CVD), and chronic kidney disease (CKD) as Cardiovascular-Kidney-Metabolic (CKM) syndrome, which confers increased risk of major adverse cardiac and cerebrovascular events (MACCE). We evaluated temporal trends in MACCE and mortality among geriatric patients with CKM. Methods: This was a retrospective cross-sectional trend analysis performed using the National Inpatient Sample (2016–2020). Geriatric admissions (≥65 years) with CKD (ICD-10 N18.x) and ≥1 cardiometabolic risk factor (hypertension, DM, hyperlipidaemia, or obesity) were identified. MACCE components included acute myocardial infarction (I21.x), ischemic stroke (I63.x), and cardiac arrest (I46.x). Patients were classified as MACCE-positive (MACCE+ve) or MACCEnegative (MACCE−ve). Trends, demographics, comorbidities, length of stay, costs, and all-cause mortality were compared. Results: Median age was 78 (72–85) years in both MACCE+ve and MACCE−ve cohorts. The MACCE+ve group had a higher proportion of males (55.9% vs. 51.1%). From 2016–2020, MACCE incidence increased from 10.4% to 12.7%, and mortality rose from 4.6% to 6% (p-trend <0.001), with a pronounced spike in 2020 coinciding with the COVID-19 pandemic. Compared with MACCE−ve patients, MACCE+ve patients had higher in-hospital mortality (15.3% vs. 3.4%), shorter length of stay (4 vs. 5 days), and greater hospitalization costs ($66,824 vs. $43,727; p<0.001). Discussion: MACCE and mortality increased progressively in elderly CKM patients, with disproportionate burden among males, racial/ethnic minorities, and lower-income populations. It underscores the need for improved risk stratification, equitable access to healthcare, and multidisciplinary, population-specific management strategies to mitigate cardiovascular risk and mortality. Conclusion: Our analysis suggests rising trends in MACCE in CKM syndrome, which significantly impact in-hospital outcomes. Considering limited data, longitudinal studies, riskprediction models, and population-level strategies are needed to improve prevention and management in this growing geriatric population.
Introduction: Cardiovascular disease (CVD) is the leading cause of global mortality, driven by vascular dysfunction. Endothelial dysfunction, vascular inflammation, and VSMC remodeling underlie arteriosclerosis and atherosclerosis, which are accelerated in T2DM by hyperglycaemia, oxidative stress, dyslipidaemia, and chronic inflammation. Metabolic stress reprograms vascular cells, promoting oxidative damage, cytokine release, and vascular senescence, ultimately contributing to arterial stiffening, plaque instability, and intimal calcification. Understanding these immunometabolic interactions is critical for developing targeted therapies. Methods: We reviewed experimental, translational, and clinical studies, along with systematic and narrative reviews, to examine how metabolic and immune dysregulation drives vascular pathology. Results: Vascular inflammation and immunometabolic dysregulation are central drivers of CVD in T2DM. Immune–metabolic crosstalk, mechanical stress, and epigenetic regulation disrupt vascular homeostasis, causing endothelial dysfunction, VSMC phenotypic switching, extracellular matrix remodelling, arterial stiffening, and atherogenesis. Key factors—cytokine/chemokine signalling (IL-1β, IL-6, TNF-α), vasoactive hormones, metabolic blood components, mechanical stress, and epigenetic dysregulation—converge on pathways including oxidative stress, NF- κB and PI3K/AKT signalling, HIF-1α activation, AGE–RAGE interactions, inflammasome activation, and foam cell formation. Crosstalk among endothelial cells, macrophages, VSMCs, and adaptive immune cells drives plaque progression and vascular remodelling. Emerging mechanisms such as trained immunity and clonal haematopoiesis reveal persistent vascular inflammation and novel therapeutic targets. Pharmacological interventions—including GLP-1 receptor agonists, SGLT2 inhibitors, statins, RAAS blockers, and IL-1β inhibitors—alongside lifestyle measures, confer vascular protection beyond glycaemic control. Discussion: Immunometabolic dysregulation promotes persistent vascular inflammation, arterial stiffening, VSMC remodelling, and plaque progression. Mechanisms, including trained immunity and clonal haematopoiesis, contribute to residual cardiovascular risk, highlighting the need for integrated strategies targeting both metabolic and inflammatory pathways. Conclusion: Vascular dysfunction in T2DM arises from metabolic stress, immune activation, and vascular cell reprogramming. Trained immunity and clonal haematopoiesis provide insight into persistent vascular inflammation and residual cardiovascular risk. Combined pharmacological and lifestyle interventions, guided by integrative omics, offer precision strategies to reduce CVD risk. Future research should address cell-specific mechanisms, regulation of immune memory, and long-term outcomes to optimize cardiometabolic care.
Background: Flecainide is a class Ic antiarrhythmic and is commonly used in rhythm control in patients with AF without structural heart disease. It is usually well tolerated when used properly, but may cause major conduction anomalies, including rare incidences of bradyarrhythmia. Case Presentation: The case of a 37-year-old man without a history of previous cardiac events was reported, who presented with dyspnoea and palpitations. Primary assessment indicated narrow- complex tachycardia with a PR interval longer than the RP interval. After the trial of intravenous metoprolol without success in managing the rate, AF was diagnosed, and flecainide 200mg/day was started. In two weeks, the patient experienced frequent syncope without premonitory symptoms. Even the primary follow-up ECG showed a prolonged QT interval and a slowed ventricular rate. Echocardiography revealed normal LV function and LA enlargement; coronary angiography did not reveal any obstructive disease. Flecainide was discontinued, and the rhythm changed to persistent AF with no additional syncope during 6 months of follow-up. Conclusion: The current case involves a rare case of therapeutic-dose flecainide-induced bradycardia and syncope in a normal heart structure. It highlights the need to monitor early postinitiation ECGs and be attentive to changes in conduct, even in low-risk patients, before they become life-threatening complications.
Introduction: Many older adults with peripheral vascular disease (PVD) have multiple comorbidities and often experience worse outcomes after a heart attack (MI). Intravascular ultrasound (IVUS) is sometimes used during percutaneous coronary intervention (PCI) to better visualize the coronary arteries and identify blockages. However, it remains unclear how frequently IVUS is used in these patients or whether it improves outcomes for elderly PVD patients undergoing PCI for MI. Methods: We analyzed data from the National Inpatient Sample database for the years 2016 to 2020. The study included patients aged 65 or older with peripheral vascular disease (PVD) who were hospitalized for a heart attack (MI) and underwent PCI. We identified these patients using ICD-10 codes and divided them into groups based on whether IVUS was used during PCI. We compared their baseline characteristics, tracked changes in IVUS use over time, and reviewed their hospital outcomes. The main outcome measured was death from any cause during the hospital stay. We used statistical methods to account for differences in patient backgrounds, hospital types, and other health conditions. Results: From 2016 to 2020, 117,245 older patients with PVD who experienced a heart attack underwent PCI. IVUS was used in 10,345 cases, representing 8.8%. Most patients were men (62.1%) and White (83.2%). IVUS use increased each year among both men and women and across racial groups. After adjusting for other factors, IVUS use did not result in a significant reduction in in-hospital deaths compared to PCI without IVUS. However, among those who had IVUS-guided PCI, men had lower in-hospital death rates than women. Discussion: Although IVUS use increased over time, it was not associated with better short-term survival in these older PVD patients. The differences between men and women may be related to heart anatomy, blood vessel size, disease severity, or other factors not fully captured in the data. Conclusion: IVUS is now used more frequently during PCI in older PVD patients with heart attacks. However, we did not find a clear benefit in reducing in-hospital deaths. The differences in outcomes between men and women suggest that IVUS may not have the same effect for all patients. More longterm studies are needed to determine which patients benefit most from IVUS.
Introduction/Objective: Heart Failure with Preserved Ejection Fraction (HFpEF) is increasingly recognized as a metabolic disorder. This review investigates the role of ceramidemediated lipotoxicity in its pathogenesis, focusing on how aberrant ceramide accumulation drives myocardial dysfunction. Methods: We synthesized and critically evaluated current preclinical and clinical literature from major electronic databases (PubMed/MEDLINE, Embase, Web of Science) up to March 2026. Using a hierarchical evidence classification framework (Level 1: human HFpEF myocardium; Level 2: HFpEF-specific animal models; Level 3: related disease models; Level 4: in vitro studies), we analyzed evidence across calcium handling, apoptosis, autophagy, inflammation, and fibrosis pathways. Results: Ceramide lipotoxicity represents an important pathological nexus. It directly impairs cardiomyocyte function by disrupting calcium homeostasis and ion channels (SERCA2a, RyR2, Kv4.3). Concurrently, it triggers mitochondrial and death receptor-mediated apoptosis, inhibits autophagic flux via AMPK/mTORC1 dysregulation, and activates pro-inflammatory (NF-κB, IL-6, TNF-α) and pro-fibrotic (TGF-β/Smad3) signaling pathways. These mechanisms collectively lead to diastolic dysfunction and disease progression. Interventions targeting ceramide synthesis (SPT inhibitors) or downstream effects show therapeutic promise in experimental models. Discussion: The available evidence is derived predominantly from Level 3 models (diabetic cardiomyopathy, obesity-induced dysfunction) and Level 4 in vitro studies. Direct validation in human HFpEF myocardium (Level 1) and HFpEF-specific animal models (Level 2) remains a critical unmet need. The ceramide-centered hypothesis is most directly applicable to the metabolic/obesity-related phenotype of HFpEF, given the phenotypic heterogeneity of the syndrome. Therapeutic translation faces hurdles, including a lack of tissue selectivity, ceramide species complexity, and unknown long-term safety of inhibiting essential sphingolipid functions Conclusion: Ceramide-mediated lipotoxicity constitutes a significant pathogenic mechanism in the metabolic phenotype of HFpEF. However, this conclusion is largely inferred from preclinical models recapitulating metabolic stress. Direct validation in human HFpEF myocardium is urgently needed. Future research must prioritize human tissue lipidomics, development of multifactorial animal models, and targeted clinical trials to translate these findings into effective therapies.
BACKGROUND:Coronary artery disease (CAD) is a leading cause of mortality worldwide, with long-term outcomes heavily dependent on secondary prevention. Poor adherence to guideline-directed therapy and unhealthy dietary practices significantly increase the risk of recurrent ischemic events, restenosis, and heart failure. Long-term success after percutaneous coronary intervention depends heavily on continuous adherence to medical therapy and lifestyle modification. CASE PRESENTATION:This study reports the case of a 63-year-old Indian male with diabetes and hypertension who previously underwent percutaneous coronary intervention in 2014 for myocardial infarction. In 2018, the patient stopped taking both dual antiplatelet therapy and statins and changed to a completely open dietary plan with a large amount of saturated fat in his diet. By 2025, he had unstable angina, which was ultimately diagnosed as a non-ST-elevation myocardial infarction. During coronary angiography, he was found to have significant triple-vessel disease, including in-stent restenosis and a left ventricular ejection fraction of 25% to 35%. As a result, after revascularization, he was treated with a combination of dual antiplatelet therapy, a high-intensity statin, sacubitril/valsartan, and a sodium-glucose cotransporter-2 Inhibitor. While initially all medications were successfully managed, the patient was ultimately found to have irreversible myocardial dysfunction due to prolonged nonadherence with proper management and lifestyle modifications. CONCLUSIONS:This case highlights the potential long-term consequences of discontinuing prescribed cardiac medications and neglecting dietary advice after revascularization. Although multiple factors such as progression of diabetes, metabolic disturbances, and recurrent ischemia may contribute to ventricular dysfunction, prolonged interruption of guideline-directed therapy and periodic assessment of therapeutic targets likely played an important role in the progression of coronary disease and development of heart failure.
INTRODUCTION:The association between the gut microbiota and aortic dissection(AD) progression remains to be fully characterized, and current evidence regarding the influence of cortisol on this relationship remains inconclusive. The aim of this study was to determine whether cortisol levels contribute to this association. METHODS:A two-sample Mendelian Randomization (MR) approach was implemented, incorporating gut microbiota summary statistics derived from a large-scale genome-wide association meta-analysis (n=18,340) performed by the MiBioGen consortium. Additionally, summary-level data on aortic dissection were obtained from the FinnGen Consortium R10 release, which included 967 cases and 381,977 controls. To investigate causal relationships, the study implemented inverse-variance weighting, a weighted model, a weighted median, MR-Egger, and MRPRESSO. Mediated MR analyses were performed on bacteria identified as causally associated with aortic dissection, along with intermediate metabolites derived from 1,400 blood metabolites, and the metabolites that mediated the relationship between them were identified. The study employed Cochran's Q test to examine heterogeneity in the genetic instruments. RESULTS:Seven gut microbiota species with elevated abundance potentially exerts a protective or negative effect on aortic dissection. In particular, the Ruminococcus gnavus group may have a deleterious effect on aortic dissection via changes in cortisol levels. CONCLUSION:This study offers novel insights into the involvement of gut microbiota in the prevention of aortic dissection and the complex relationship between them. Additionally, it underscores the significance of randomized controlled trials in determining the association linking gut microbiota with aortic dissection risks.
Coronary artery disease (CAD) is a leading cause of mortality worldwide, driven by both environmental and genetic factors. Over the past two decades, our understanding of CAD vulnerability has increased substantially through advancements in genetic investigations. Researchers have extensively examined the genetic basis of CAD through genome-wide association studies (GWAS), identifying numerous loci associated with the disease. The findings have facilitated the early identification of at-risk individuals and the implementation of targeted prevention strategies, while also helping to uncover the pathophysiology of the disease. Despite these advancements, converting genetic discoveries into clinical applications still poses challenges. This review examines the heritable underpinnings of CAD, focusing on the contributions of GWAS to our understanding of the disease. The GWAS methodology, key findings, functional implications, and future prospects are discussed, along with the current status. It highlights how GWAS findings are paving the way for personalized medicine through polygenic risk scores, targeted therapies, and pharmacogenomics-driven interventions for CAD.
INTRODUCTION:The growing demand for cardiovascular medical devices (CMDs) has significantly improved the quality of life for patients with heart disease. Despite major technological advances, long-term performance is still hindered by complications arising from interactions between blood and material, such as thrombosis, chronic inflammation, endothelial dysfunction, infection, and fibrotic encapsulation. But issues such as thrombosis, inflammation, cytotoxicity, and infection, primarily brought about by poor surface compatibility with biological fluids and tissues, are often the reasons for the inability of these devices to achieve long-term success. METHODS:A structured literature review was conducted following PRISMA 2020 guidelines using PubMed, Scopus, Web of Science, and Google Scholar (2020-2025). Studies on surfacemodified cardiac implants (stents, valves, pacemaker leads, and LVADs) evaluating biocompatibility, hemocompatibility, or infection resistance were included, while non-cardiac and unrelated nanocarrier studies were excluded. Extracted data were narratively synthesised to compare coating mechanisms, durability, and translational potential. RESULTS:Heart valves, stents, pacemakers, and ventricular assist devices, among other CMDs, have seen surface modification and coating technologies evolve as critical instruments to enhance the biocompatibility, hemocompatibility, and functionality of CMDs. A total of 115 screened reference records demonstrated significant evidence of CMD-related bioactive strategies. DISCUSSION:In this paper, a systematic review of a wide range of surface engineering strategies, such as passive and bioactive coatings, proven techniques like heparin immobilisation, albumin functionalization, nitric oxide release systems, and zwitterionic polymers, is provided with specific emphasis. The review also addresses challenges related to device-associated infections, complement activation, and immune responses. CONCLUSION:Ultimately, this review aims to be a comprehensive guide for selecting appropriate surface modifications for CMDs and highlights future directions to enhance clinical outcomes through the use of next-generation multifunctional coatings.
INTRODUCTION:The constantly evolving nature of diseases has put humanity in a never- ending struggle for survival, adapting to each disease and fighting the silent battles with strength. Similarly, the complex cardiovascular system needs constant monitoring to prevent potential complications of inflammation, disrupted immune responses, blockages, heart attacks, angina, and other life-threatening conditions that end up triggering acute coronary syndrome (ACS). Its symptoms range from mild to severe and are typically challenging to identify, so early detection is crucial for successful treatment and prevention. To obtain a more precise and critical understanding of the potential genetic factors contributing to developing ACS, researchers use advanced and innovative approaches, like AlphaFold and artificial intelligence. METHODS:Comprehensive knowledge about the integration of AlphaFold (AF) and artificial intelligence (AI) has been provided in this study, as it has completely changed how proteins interact by reliably predicting their three-dimensional structures from the order of their amino acids. Additionally, the role of immune cells in the progression of ACS has been discussed, along with therapeutic measures to treat ACS with next-generation sequencing (NGS). RESULTS:The results have shown ischemia, plaque rupture, erosion, and thrombus formation to be the primary causes of ACS. These factors make the immune system's optimal function even more complicated, making it harder for researchers to find effective treatments for ACS patients. DISCUSSION:The AlphaFold and AI have provided significant insights into the molecular mechanisms underlying ACS, highlighting the complex interplay between genetic factors and immune responses. CONCLUSION:This article has explored the potential of AlphaFold and AI in understanding the immunological mysteries of ACS, aiming to aid future therapeutic studies and reduce cardiovascular disease burden.
