Cardiology In Review[JOURNAL]
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200 papers
Danon Disease: Clinical Manifestations, Pathophysiology, and Treatment.
Richards M, Tetelbaun L, Frishman WH
Cardiol Rev · 2026 Mar · PMID 41913263 · Publisher ↗
Danon disease is an X-linked dominant vacuolar disease caused by a mutation in lysosome-associated membrane protein-2 (LAMP-2). LAMP-2 has 3 known subtypes, with LAMP-2B being the most important in Danon disease. It play...
Danon disease is an X-linked dominant vacuolar disease caused by a mutation in lysosome-associated membrane protein-2 (LAMP-2). LAMP-2 has 3 known subtypes, with LAMP-2B being the most important in Danon disease. It plays a role in macroautophagy and is one of the reasons why those with Danon disease have issues degrading cytoplasmic components. Autophagic vacuoles with unique sacrolemmal features are a characteristic finding in Danon disease. This condition is rare but causes fatal cardiomyopathy in those it affects. It is known to cause a triad of intellectual disability, cardiomyopathy, and skeletal myopathy in males, but is mostly restricted to cardiomyopathy in females. The cardiomyopathy is most often hypertrophic cardiomyopathy, but can also be dilated cardiomyopathy, especially in females. Both ventricular and atrial arrhythmias are common in those with Danon disease. They commonly have slurring of the upstroke of the QRS complex, or ventricular depolarization, on electrocardiogram and extensive late gadolinium uptake with mid-interventricular septal sparing on cardiac magnetic resonance imaging. Treatment currently consists of heart transplant, and gene therapy studies are in phase II clinical trials using RP-A501, a recombinant adeno-associated virus-9 containing the transgene LAMP-2, to deliver LAMP-2 to cardiomyocytes.
Poly(ADP-Ribose) Polymerases Inhibition in Cardiovascular Oncology: Protective Mechanisms Versus Clinical Cardiotoxicity.
Thukral J, Moudgil P, Ratol HK … +9 more , Moudgil S, Anupama F, Sindhwani N, Dhawan A, Shah RK, Kaur H, Thukral N, Frishman WH, Aronow WS
Cardiol Rev · 2026 Mar · PMID 41913256 · Publisher ↗
Poly(ADP-ribose) polymerases (PARPs) are central components of the cellular DNA damage response, coordinating DNA repair, chromatin remodeling, and transcriptional regulation. Beyond their established role in oncology, a...
Poly(ADP-ribose) polymerases (PARPs) are central components of the cellular DNA damage response, coordinating DNA repair, chromatin remodeling, and transcriptional regulation. Beyond their established role in oncology, accumulating evidence identifies PARP-particularly PARP-1-as a key modulator of cardiovascular stress responses. In cardiovascular disease states characterized by oxidative and nitrosative stress, PARP activation exerts context-dependent effects: while moderate activation supports genomic integrity and cell survival, excessive or sustained PARP activity leads to depletion of nicotinamide adenine dinucleotide and adenosine triphosphate, mitochondrial dysfunction, inflammatory signaling, and cardiomyocyte death. Preclinical studies consistently demonstrate that genetic or pharmacologic PARP inhibition attenuates ischemia-reperfusion injury, reduces infarct size, limits adverse ventricular remodeling, and preserves myocardial energetics, supporting a cardioprotective role for transient PARP modulation. However, clinical experience with PARP inhibitors, primarily derived from their use in breast cancer susceptibility gene-mutant and homologous recombination-deficient cancers, reveals a more complex cardiovascular safety profile. Pharmacovigilance analyses and real-world data have reported associations with hypertension, thromboembolic events, arrhythmias, and major adverse cardiovascular events, particularly with prolonged systemic exposure and in patients with preexisting cardiovascular comorbidities. This apparent discordance underscores the importance of timing, duration, tissue specificity, and agent-dependent effects in determining cardiovascular outcomes.
Transcatheter Versus Surgical Aortic Valve Replacement in Patients With Symptomatic Severe Aortic Stenosis and Prior Mediastinal Radiation: A Meta-Analysis of Short-Term and 1-Year Outcomes.
Elbenawi H, Mostafa N, Abdelgalil MS … +14 more , Dahik B, Mohamed Hamed B, Botros MM, Eisa M, Zreigh S, Kalaiger AM, Almaadawy O, Youssef M, Zaaya M, Stephens R, Ghanim M, Lin CJ, Elgendy IY, Goldsweig AM
Cardiol Rev · 2026 Mar · PMID 41913240 · Publisher ↗
Mediastinal radiation potentiates aortic stenosis and complicates its treatment. We compared the short and midterm-outcomes with transcatheter aortic valve replacement (TAVR) versus surgical aortic valve replacement (SAV...
Mediastinal radiation potentiates aortic stenosis and complicates its treatment. We compared the short and midterm-outcomes with transcatheter aortic valve replacement (TAVR) versus surgical aortic valve replacement (SAVR) in patients with prior mediastinal radiation. Electronic databases were searched from inception through December 2024. Dichotomous outcomes were pooled as risk ratios (RRs), and continuous outcomes were pooled as mean differences (MDs) with respective 95% confidence intervals (CIs). Six observational studies were identified, including 2458 TAVR patients and 1873 SAVR patients. In the short-term, TAVR was associated with lower rate of mortality (RR: 0.54; 95% CI: 0.34-0.88), atrial fibrillation (RR: 0.31; 95% CI: 0.15-0.65), acute kidney injury (RR: 0.75; 95% CI: 0.59-0.95), bleeding (RR: 0.37, 95% CI: 0.33-0.42), and shorter length of hospital stay (MD: -4.30; 95% CI: -5.45 to -3.15). One-year mortality was comparable between the 2 groups (RR: 1.04; 95% CI: 0.50-2.13). This meta-analysis of observational studies of patients with prior mediastinal radiation demonstrated that TAVR was associated with better short-term outcomes compared to SAVR. While 1-year mortality appeared similar between the 2 interventions, this finding should be interpreted with caution. However, randomized controlled trials are needed to validate these findings.
Processed Foods and Food Dyes: What Are We Eating and What Is the Cardiovascular Risk?
Kaiser ME, Parikh MA, Turitto G … +3 more , Grutman G, Frishman WH, Peterson SJ
Cardiol Rev · 2026 Mar · PMID 41879811 · Publisher ↗
Ultra-processed foods (UPFs) are industrially manufactured products that contain several additives and may contain high levels of added sugar, fat, salt, or little whole food. They also represent an increasing percentage...
Ultra-processed foods (UPFs) are industrially manufactured products that contain several additives and may contain high levels of added sugar, fat, salt, or little whole food. They also represent an increasing percentage of the world's diet and are increasingly associated with the development of cardiovascular disease (CVD). The findings of several meta-analyses and extensive, population-based longitudinal studies suggest there is a dose-response relationship between UPF consumption and each of the following outcomes: CVD, stroke, and total CVD-related deaths. Some food additives, especially emulsifiers (like carboxymethylcellulose and mono- and diglycerides), preservatives (like carboxymethylcellulose and mono- and diglycerides), and artificial colors (like tartrazine and sunset yellow), have been proven to independently alter the gut microbiome, induce cellular oxidative stress, and enhance chronic low-level low-grade inflammation. A common mechanistic pathway involves activation of the nuclear factor kappa B family of transcription factors, which mediate the production of pro-inflammatory cytokines, induce endothelial dysfunction, and promote atherogenesis. Thus, reducing UPF serves as a modifiable target for CVD prevention, can be incorporated into dietary guidelines and food-labeling practices to influence public health policy.
Revascularization Strategies for Ostial Left Anterior Descending Artery Chronic Total Occlusion: A Comprehensive Review.
Refaat MM, Hasan I, Hasan N … +4 more , Al Sakan M, Moussallem N, Shaheen M, Ghazzal Z
Cardiol Rev · 2026 Mar · PMID 41879808 · Publisher ↗
Chronic total occlusion (CTO) is encountered in about one quarter of patients undergoing coronary angiography and is associated with significant clinical and technical revascularization challenges. Among CTOs, ostial lef...
Chronic total occlusion (CTO) is encountered in about one quarter of patients undergoing coronary angiography and is associated with significant clinical and technical revascularization challenges. Among CTOs, ostial left anterior descending (LAD) occlusion represents a rare and particularly high-risk subset, owing to the large myocardial territory at risk and the unique anatomical and procedural difficulties encountered. These include ambiguous lesion morphology, heavy calcification, lack of a clear entry point, and increased risk of complications during revascularization. Data on optimal management remain scarce, with limited comparative evidence between different percutaneous coronary intervention (PCI) approaches, or regarding the comparison between PCI and coronary artery bypass grafting in this subset of patients. This comprehensive review synthesizes the current literature on the management of ostial LAD CTO, highlights procedural strategies and outcomes, and identifies existing knowledge gaps to guide clinical decision-making and future research. Available evidence suggests that the antegrade approach is generally preferred in less complex lesions, while retrograde strategies are reserved for stumpless, calcified, or anatomically complex occlusions. However, the absence of prospective randomized trials and the lack of dedicated comparisons between PCI and coronary artery bypass grafting in this population represent major limitations. Future large-scale studies are warranted to establish standardized treatment algorithms and define the optimal revascularization strategy for ostial LAD CTO.
The Efficacy and Safety of Cilostazol as an Alternative Antiplatelet Therapy After Coronary Stent Implantation in Patients With Aspirin Intolerance.
Mootz N, Dugaesescu A, Rehman H … +4 more , Samayam N, Andes B, Hansen T, Lin CJ
Cardiol Rev · 2026 Mar · PMID 41872117 · Publisher ↗
Aspirin (ASA) is commonly used in dual antiplatelet therapy (DAPT) of patients undergoing percutaneous coronary intervention. The pharmacologic management in the patient demographic with an ASA intolerance is poorly defi...
Aspirin (ASA) is commonly used in dual antiplatelet therapy (DAPT) of patients undergoing percutaneous coronary intervention. The pharmacologic management in the patient demographic with an ASA intolerance is poorly defined. This study aims to determine the efficacy and safety of the phosphodiesterase-3 inhibitor, cilostazol, as an alternative DAPT for ASA-intolerant patients. We used PubMed, Google Scholar, and Cochrane until January 2024 to identify all related prospective and retrospective studies evaluating cilostazol antiplatelet therapy in ASA-intolerant patients. Studies that did not include the target population were excluded. Fixed and random effect models with the Mantel-Haenszel statistical method were used to calculate P values, risk ratios, Z scores, and a 95% confidence interval on RevMan 7.14.0 software. Cilostazol use demonstrates a significant decrease in the incidence of major adverse cardiac events ( P = 0.02) (relative risk [RR] = 0.71 [0.53, 0.94]). A nonsignificant trend for benefit was identified for incidence of myocardial infarction ( P = 0.34) (RR = 0.42 [0.07, 2.46]) and major bleeding event (P = 0.71) (RR = 0.65 [0.07, 6.37]). The findings of this study suggest a potential benefit for the use of cilostazol in patients after percutaneous coronary intervention with aspirin intolerance.
Management of Arrhythmias in Older Adult Patients ≥75 Years Old Compared to Younger Patients <75 Years Old: Is Contemporary Practice Reflective of Evidence?
Yuyun MF, Joseph J, Kinlay S … +5 more , Peralta AO, Hoffmeister PS, Singh JP, Gaziano JM, Orkaby AR
Cardiol Rev · 2026 Mar · PMID 41870966 · Publisher ↗
The burden of arrhythmias, like most cardiovascular diseases, increases with age, and risks of arrhythmias-associated adverse outcomes, including all-cause mortality, are greater in older adult patients compared with you...
The burden of arrhythmias, like most cardiovascular diseases, increases with age, and risks of arrhythmias-associated adverse outcomes, including all-cause mortality, are greater in older adult patients compared with younger patients. Older adult patients (≥75 years old) and patients with cognitive impairment tend to be either significantly underrepresented or systematically excluded from major randomized controlled trials of invasive arrhythmia management. In key arrhythmia clinical trials, the average age of participants has been principally in the 60s, except for studies of oral anticoagulation in atrial fibrillation/flutter, where older adult patients were adequately recruited. Therapies emanating from the findings of these clinical trials, deduced from predominantly younger patients, tend to be speculatively applied to older adult patients, most often with scant or without randomized controlled trial evidence in these patients. While observational studies have provided some reassuring evidence of the usefulness of certain arrhythmia management strategies in older adults, these are often associated with increased risk of adverse outcomes compared with younger patients. These deleterious outcomes have been observed to be more marked in older adult patients with premature biological aging (characterized by increased frailty or high comorbidity burden or other measures). Therefore, uncertainty remains about the benefits and risks of some invasive arrhythmia management in elderhood. This narrative review critically summarizes the current evidence surrounding the efficacy and safety of arrhythmia management in older adult patients ≥75 years old compared with those younger patients <75 years old. It also identifies any significant discrepancies in arrhythmia treatment patterns between the older and younger population and their outcomes.
Updates in the Treatment of Pediatric Pulmonary Arterial Hypertension.
Jafri DZ, Beck JM, Kaplan SA … +8 more , Keeler A, Sanchez B, Brady D, Frishman WH, Aronow WS, Levine A, Rosenzweig E, Lanier GM
Cardiol Rev · 2026 Mar · PMID 41870911 · Publisher ↗
Pediatric pulmonary arterial hypertension (PAH) is a relentless and potentially fatal disease marked by elevated pulmonary vascular resistance and pulmonary pressure as a result of unchecked vascular remodeling, prolifer...
Pediatric pulmonary arterial hypertension (PAH) is a relentless and potentially fatal disease marked by elevated pulmonary vascular resistance and pulmonary pressure as a result of unchecked vascular remodeling, proliferation, and dysfunction. While pharmacological treatment algorithms for adult PAH are well-established and frequently updated, pediatric PAH treatment guidelines in the United States are generally based on limited clinical trials and expert opinion, leaving clinicians to extrapolate from adult data and expert consensus rather than pediatric-specific, evidence-based protocols. Endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and prostacyclin-pathway agents remain the therapeutic cornerstone, yet clinical practice is being reshaped by pivotal therapeutic developments. Recent advances highlight differences in monotherapy versus combination pharmacological regimens, alongside active trials investigating interventional/surgical procedures in the amelioration of long-term outcomes. This review seeks to consolidate contemporary data and clinical trial highlights to reflect a necessary shift toward precise, developmentally informed pharmacotherapy in children, underscoring the pressing need for an updated pharmacological guideline that incorporates pediatric-specific trials and harmonizes labeling and long-term safety surveillance in the treatment of pediatric PAH.
The Updated 2025-2030 Dietary Guidelines for Americans: A Review of Cardiovascular Health Implications.
Whiteson HZ, Whiteson J, Frishman WH
Cardiol Rev · 2026 Mar · PMID 41870906 · Publisher ↗
The Dietary Guidelines for Americans represent a cornerstone of public health policy that has recently undergone substantial revision, introducing significant modifications to the recommended types, quantities, and propo...
The Dietary Guidelines for Americans represent a cornerstone of public health policy that has recently undergone substantial revision, introducing significant modifications to the recommended types, quantities, and proportional distributions of food groups for the American population. The introduction of these updated guidelines has generated considerable discourse within the medical and scientific communities, with stakeholders offering differing perspectives on their scientific merit and potential public health impact. The evaluation of these dietary recommendations assumes urgency when considered within the epidemiological context of cardiovascular disease, which continues to represent the predominant cause of morbidity and mortality among United States citizens. This comprehensive review provides a systematic and critical analysis of the updated Dietary Guidelines for Americans through a cardiovascular lens. We elucidate areas where the guidelines demonstrate scientific rigor and alignment with contemporary evidence. We also identify potential shortcomings, gaps in evidence translation, and opportunities for future refinement that are essential for clinicians, policymakers, and public health professionals engaged in cardiovascular disease prevention efforts.
Effect of Fluid Restriction in Heart Failure: A Meta-Analysis of Randomized Controlled Trials.
Sajid M, Ahmed S, Khan TM … +6 more , Salim H, Husseiny YM, Qureshi S, Sajjad A, Bilal AR, Waqas SA
Cardiol Rev · 2026 Mar · PMID 41860314 · Publisher ↗
Fluid restriction is frequently recommended for patients with heart failure (HF) to prevent volume overload, yet its clinical benefit remains uncertain. This meta-analysis compared the efficacy and safety of fluid restri...
Fluid restriction is frequently recommended for patients with heart failure (HF) to prevent volume overload, yet its clinical benefit remains uncertain. This meta-analysis compared the efficacy and safety of fluid restriction versus liberal fluid intake in HF by systematically searching PubMed, Scopus, and Cochrane CENTRAL through May 2025 for randomized controlled trials evaluating fluid restriction (≤1.5 L/d) compared with liberal intake in adults with HF. Outcomes included re-hospitalization, mortality, weight, thirst, quality of life (QoL), intravenous diuretic use, and serum biomarkers such as sodium, creatinine, and brain natriuretic peptide. Ten randomized controlled trials involving 1465 participants (731 fluid restriction; 734 liberal intake) were included. Fluid restriction was associated with a 29% relative reduction in re-hospitalization (relative risks [RR] 0.71; 95% confidence interval [CI], 0.50-1.02; P = 0.06; I2 = 52%) and mortality (RR 0.71; 95% CI, 0.43-1.18; P = 0.19; I2 = 0%), although neither reached statistical significance. Weight reduction favored fluid restriction (weighted mean difference [WMD] -1.58 kg; 95% CI, -3.92 to 0.76), but findings varied across studies. No significant differences were observed for thirst (WMD 4.96), QoL (standardized mean difference [SMD] 0.15), intravenous diuretic use, sodium levels (WMD 0.90 mmol/L), creatinine (WMD -0.10 mg/dL), or brain natriuretic peptide (WMD -51.41 pg/mL). Subgroup analysis showed that liberal fluid intake significantly reduced creatinine in chronic compensated HF, whereas no benefit was found in acute decompensated HF. Sensitivity analyses identified one outlier trial as the primary source of heterogeneity. Overall, fluid restriction does not significantly improve outcomes in HF, and liberal fluid intake appears safe, supporting more individualized fluid strategies.
Cardiovascular Outcomes Following Herpes Zoster Vaccination: A Systematic Review and Meta-Analysis.
Maniya MT, Farid AAM, Abid H … +11 more , Abbasi B, Afzal S, Afzaal U, Bibi M, Fatima R, Khalid H, Kumari N, Mustafa O, Nofal A, Raja AR, Sohail H
Cardiol Rev · 2026 Mar · PMID 41860309 · Publisher ↗
Herpes zoster vaccination (HZV) is primarily used to prevent the incidence of herpes zoster and its neurological complications. However, recent studies suggest a possible association with major cardiovascular events. Hen...
Herpes zoster vaccination (HZV) is primarily used to prevent the incidence of herpes zoster and its neurological complications. However, recent studies suggest a possible association with major cardiovascular events. Hence, we aimed to evaluate HZV's association with key cardiovascular outcomes. An electronic database search of PubMed, Embase, and Cochrane was carried out from inception to July 14, 2025, to find studies comparing key cardiovascular outcomes such as stroke, myocardial infarction, major adverse cardiovascular events, coronary artery disease, cardiac arrest, heart failure, and all-cause mortality in vaccinated versus unvaccinated individuals. A random-effects model was used, and pooled odds ratios (ORs) with their 95% confidence intervals (CIs) were calculated. A P value of <0.05 was considered statistically significant. A total of 9 studies were included. HZV was associated with a significantly reduced risk of stroke (OR: 0.79, 95% CI: 0.70-0.89; P = 0.0002), myocardial infarction (OR: 0.76, 95% CI: 0.65-0.89; P = 0.0005), major adverse cardiovascular events (OR: 0.77, 95% CI: 0.64-0.92; P = 0.004), coronary artery disease (OR: 0.77, 95% CI: 0.72-0.83; P < 0.00001), cardiac arrest (OR: 0.65, 95% CI: 0.44-0.98; P = 0.04), and all-cause mortality (OR: 0.56, 95% CI: 0.53-0.58; P < 0.00001). No significant associations were observed for heart failure (OR: 0.81, 95% CI: 0.58-1.14; P = 0.24). HZV was consistently associated with a reduced risk of mortality and several cardiovascular events, underscoring its potential as an effective, low-cost tool for cardiovascular disease prevention. However, high-powered studies are needed to confirm these associations.
Hereditary Angioedema.
Regis J, Parikh MA, Simon TL … +3 more , Malekan M, Frishman WH, Peterson SJ
Cardiol Rev · 2026 Mar · PMID 41860288 · Publisher ↗
Hereditary angioedema is a rare and disabling disorder caused by mutations in the SERPING1 gene. These mutations ultimately lead to deficient or dysfunctional C1 esterase inhibitor and unregulated activation of the kalli...
Hereditary angioedema is a rare and disabling disorder caused by mutations in the SERPING1 gene. These mutations ultimately lead to deficient or dysfunctional C1 esterase inhibitor and unregulated activation of the kallikrein-kinin system. This review discusses the current epidemiology, etiology, and pathophysiology of the disorder and highlights how advances in our understanding have reframed diagnostic and therapeutic strategies. We further delineate the roles of classical, alternative, and lectin complement pathways in hereditary angioedema's pathophysiology and discuss C1 esterase inhibitor within the broader serpin family context. We discuss implications for clinical practice, including diagnostic workups, genetic considerations, and targeted therapies that modulate the bradykinin pathway, aiming to shorten diagnostic timelines and optimize patient outcomes.
Ticagrelor Versus Prasugrel in Diabetes and Multivessel Coronary Disease: Insights From the TUXEDO-2 Trial.
Agrawal SP, Dunde A, Maniyar P … +6 more , Rajput J, Raval M, Maheta D, Jain H, Frishman WH, Aronow WS
Cardiol Rev · 2026 Mar · PMID 41860283 · Publisher ↗
Patients with diabetes mellitus and multivessel coronary artery disease represent a high-risk subgroup in acute coronary syndromes (ACS) requiring optimal antiplatelet therapy. Dual antiplatelet therapy with aspirin plus...
Patients with diabetes mellitus and multivessel coronary artery disease represent a high-risk subgroup in acute coronary syndromes (ACS) requiring optimal antiplatelet therapy. Dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor is the standard of care after percutaneous coronary intervention to prevent stent thrombosis and recurrent ischemic events. Ticagrelor and prasugrel are potent P2Y12 inhibitors that have each demonstrated superior efficacy over clopidogrel in large trials, though their comparative merits have been debated, especially in complex diabetic populations. This review provides background on antiplatelet therapy in ACS, with an emphasis on patients with diabetes and complex coronary anatomy; summarizes key pharmacologic differences and pivotal trial data for ticagrelor and prasugrel (including Platelet Inhibition and Patient Outcomes, TRITON-TIMI 38, and ISAR-REACT 5); and examines the design and findings of the recent TUXEDO-2 trial. TUXEDO-2, conducted in patients with diabetes with multivessel disease undergoing percutaneous coronary intervention, ticagrelor failed to meet noninferiority compared with prasugrel for a composite of ischemic and bleeding outcomes. The trial's results, in context with prior evidence, suggest that prasugrel may provide better net clinical outcomes than ticagrelor in this high-risk group. We discuss the clinical implications of these findings for managing ACS in diabetic patients.
Balancing Efficacy and Risks: A Systematic Review and Meta-Analysis of Concomitant Surgical Ablation for Atrial Fibrillation and Valve Surgery.
Biswas S, Vempati P, Wahba A … +5 more , Reza IMK, Nathan K, Elkhouly A, Hassan BD, Said SM
Cardiol Rev · 2026 Mar · PMID 41860242 · Publisher ↗
Atrial fibrillation (AF) affects 30-50% of patients undergoing valve surgery. While concomitant surgical ablation effectively restores sinus rhythm, it has been associated with an increased incidence of permanent pacemak...
Atrial fibrillation (AF) affects 30-50% of patients undergoing valve surgery. While concomitant surgical ablation effectively restores sinus rhythm, it has been associated with an increased incidence of permanent pacemakers (PPMs). No previous meta-analysis has quantified the integrated risk-benefit ratio to guide clinical decision-making. We aimed to calculate the number needed to treat (NNT) for AF freedom relative to the number needed to harm (NNH) for pacemaker implantation. Randomized controlled trials (RCTs) and observational studies comparing surgical ablation plus valve surgery versus valve surgery alone were included. Primary outcomes were freedom from AF at 12 months and PPM implantation. Freedom from AF at 12 months was selected as the primary efficacy endpoint to balance clinical relevance with methodological consistency, as longer-term outcomes were inconsistently reported across studies and could not be reliably pooled. We calculated risk ratios (RRs) with 95% confidence intervals (CIs) using random-effects meta-analysis. Thirteen studies (61,088 patients; 6 RCTs, 4 propensity-matched, and 3 observational) were included. Surgical ablation significantly increased freedom from AF at 12 months (RR, 2.96; 95% CI, 2.29-3.83; P < 0.0001; I2 = 67.4%) with NNT of 2.1. Radiofrequency ablation demonstrated superior efficacy compared to cryoablation (RR 6.22 vs 2.56, P = 0.0044). PPM implantation increased 2.77-fold (95% CI, 1.65-4.65; P < 0.001) with NNH of 15.9, yielding a favorable risk-benefit ratio of 1:7.6. No significant increases in 30-day mortality or stroke were observed among RCTs. This favorable NNT:NNH ratio of 1:7.6 supports routine concomitant ablation in appropriately selected patients with AF undergoing valve surgery.
Coronary Artery Calcium as a Biological Staging Marker for Atherosclerosis: Aligning Preventive Therapies With Plaque Evolution.
Arun AJ, Darji B, Maksymiuk V … +2 more , Baig M, Frishman WH
Cardiol Rev · 2026 Mar · PMID 41854510 · Publisher ↗
Atherosclerosis progresses silently for years, and many first cardiovascular events occur in individuals previously categorized as low or intermediate risk. Coronary artery calcium (CAC) scoring provides a direct measure...
Atherosclerosis progresses silently for years, and many first cardiovascular events occur in individuals previously categorized as low or intermediate risk. Coronary artery calcium (CAC) scoring provides a direct measure of subclinical atherosclerosis and can serve as a biologic staging marker identifying phases of plaque development in which preventive therapies exert their strongest stabilizing effects. Modern cardiometabolic therapies, including statins, proprotein convertase subtilisin/kexin type 9 inhibitors, glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter 2 inhibitors, and anti-inflammatory agents, influence plaque biology through lipid reduction, metabolic improvement, endothelial support, and attenuation of inflammatory signaling. A CAC-guided approach aligns treatment intensity with plaque burden: CAC = 0 supports lifestyle-focused prevention, CAC 1-99 identifies early disease warranting pharmacologic prevention, CAC 100-299 indicates higher-risk plaque requiring intensive lipid-lowering and adjunctive therapy, and CAC ≥300 reflects a phenotype approaching secondary prevention risk. Integrating CAC into preventive strategies enables earlier detection of atherosclerosis and disease stage-guided therapy, with the potential to reduce first cardiovascular events.
Gender Disparities in Cardiovascular Health: A Review of Risk Factors, Clinical Presentation, and Associated Outcomes.
Mathukumar A, Frishman WH, Aronow WS
Cardiol Rev · 2026 Mar · PMID 41837794 · Publisher ↗
Cardiovascular disease (CVD) remains the leading cause of death globally and accounts for approximately one-third of all global deaths. Coronary artery disease is the most common type of CVD; 1 in 20 adults ages 20 and o...
Cardiovascular disease (CVD) remains the leading cause of death globally and accounts for approximately one-third of all global deaths. Coronary artery disease is the most common type of CVD; 1 in 20 adults ages 20 and older has coronary artery disease. This literature review will examine the sex and gender disparities that exist regarding risk factors, clinical presentation, and clinical outcomes of CVD. Traditional and nontraditional risk factors of CVD that are highlighted include smoking, diabetes, high blood pressure, dyslipidemia, obesity, depression, psychosocial factors, autoimmune disease, and physical inactivity. These risk factors affect both sexes but lead to a disproportionately higher risk of CVD in women. Female-specific risk factors, such as hypertensive disorders of pregnancy, and male-specific risk factors, such as testosterone deficiency, also demonstrate associations with CVD risk. Biological, structural, and hormonal differences between men and women are also prominent and significantly affect the progression of cardiovascular health. Improved recognition of sex-based differences in risk and presentation is essential for reducing morbidity and mortality as it relates to cardiovascular health.
The Calcineurin-Nuclear Factor of Activated T Cells Signaling Axis in Hypertrophic Cardiomyopathy: Molecular Insights and Therapeutic Implications.
Agrawal SP, Maniyar P, Jairaj Varshi R … +5 more , Khan A, Maheta D, Siddiq S, Frishman WH, Aronow WS
Cardiol Rev · 2026 Mar · PMID 41837787 · Publisher ↗
Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disorder characterized by maladaptive myocardial hypertrophy, fibrosis, and an increased risk of arrhythmias and sudden cardiac death. Although HCM arises f...
Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disorder characterized by maladaptive myocardial hypertrophy, fibrosis, and an increased risk of arrhythmias and sudden cardiac death. Although HCM arises from mutations in sarcomeric proteins, accumulating evidence indicates that downstream calcium-dependent signaling pathways drive pathological remodeling. Among these, the calcineurin-nuclear factor of activated T cells (NFAT) axis has emerged as a central mediator linking altered calcium handling and mechanical stress to hypertrophic gene transcription. Experimental studies in transgenic animals, human myocardial tissue, and induced pluripotent stem cell-derived cardiomyocytes demonstrate that sustained calcineurin activation promotes NFAT nuclear translocation and reactivation of fetal gene programs characteristic of HCM. Pharmacologic inhibition of calcineurin attenuates pathological hypertrophy in multiple preclinical models, although systemic toxicity and inconsistent efficacy limit clinical translation. Consequently, novel therapeutic strategies, including cardiac-targeted gene therapy, NFAT decoy oligonucleotides, peptide-based inhibitors, and modulation of regulatory signaling nodes, have been developed to achieve pathway-specific suppression with improved safety. Despite challenges related to signaling redundancy, disease heterogeneity, and optimal timing of intervention, selective targeting of calcineurin-NFAT signaling represents a promising disease-modifying approach for HCM, with the potential to shift management beyond symptomatic treatment toward precision-based molecular therapy.
Second-Generation and Off-the-Shelf CAR Platforms: Emerging Cardiovascular Implications of Next-Generation Cellular Immunotherapies.
Thukral J, Moudgil P, Mann A … +10 more , Goyal T, Sindhwani N, Shah RK, Chandani KU, Kaur H, Thukral N, Raval M, Agrawal SP, Frishman WH, Aronow WS
Cardiol Rev · 2026 Mar · PMID 41837781 · Publisher ↗
Chimeric antigen receptor (CAR)-based therapies have become an integral part of modern cancer care, delivering durable responses in patients with otherwise refractory hematologic malignancies. As their use has expanded,...
Chimeric antigen receptor (CAR)-based therapies have become an integral part of modern cancer care, delivering durable responses in patients with otherwise refractory hematologic malignancies. As their use has expanded, it has become increasingly clear that these immune-based treatments exert important effects on the cardiovascular system. Rather than reflecting isolated cardiac injury, CAR-associated cardiovascular complications arise from a broader inflammatory process in which immune activation, cytokine release, endothelial dysfunction, and myocardial stress are closely interconnected. Pro-inflammatory mediators such as interleukin-6, interleukin-1β, tumor necrosis factor-α, and interferon-γ play central roles in shaping these responses, particularly during cytokine release syndrome. From a clinical perspective, cardiovascular manifestations often include hypotension, arrhythmias, and transient reductions in left ventricular function, with more severe presentations occurring in patients who develop high-grade inflammatory toxicity. At the same time, advances in immune engineering are reshaping how these platforms are viewed, extending their relevance beyond toxicity alone. Preclinical studies now suggest that CAR-based approaches may be adapted to modulate cardiac fibrosis and promote myocardial repair, highlighting a potential shift from purely oncologic applications toward broader cardiovascular benefit. Placing these developments within a cardio-oncology framework emphasizes the need for careful cardiovascular assessment, longitudinal monitoring, and close collaboration between specialties.
The Association of Diabetes and Coronary Artery Ectasia: A Systematic Review and Meta-Analysis.
Molavizade S, Dehghani F, Mirbod SM … +5 more , Amini A, Udensi CG, Noroozi M, Mahjoubi M, Keykhaei M
Cardiol Rev · 2026 Mar · PMID 41813629 · Publisher ↗
Coronary artery ectasia (CAE) is a coronary abnormality characterized by arterial dilation, with inflammation, hypertension, dyslipidemia, and diabetes hypothesized to be implicated in its pathogenesis. The exact relatio...
Coronary artery ectasia (CAE) is a coronary abnormality characterized by arterial dilation, with inflammation, hypertension, dyslipidemia, and diabetes hypothesized to be implicated in its pathogenesis. The exact relationship between CAE and diabetes remains unclear, with previous studies reporting contradictory findings. We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO: CRD42024627403). Four databases (PubMed, Scopus, Web of Science, and Embase) were searched up to October 2024. Eligible studies included angiographically diagnosed CAE cases and controls with reported diabetes prevalence. Relative risks (RR) were calculated for diabetes, hypertension, and dyslipidemia; mean differences for body mass index and fasting blood sugar. Subgroup analyses compared isolated versus nonisolated CAE. Forty-six studies consisting of 6215 CAE patients and 59,484 non-CAE controls were included. Pooled results showed no significant association between diabetes and CAE (RR, 1.00; 95% CI, 0.88-1.13; I2, 76.65%; P = 0.95). Subgroup analyses showed no association in isolated CAE (RR,= 1.10; 95% CI, 0.92-1.32; I2, 50.45%; P = 0.31) or nonisolated CAE (RR, 0.84; 95% CI, 0.68-1.04; I2, 82.31%; P = 0.12). Fasting blood sugar analysis showed no significant difference between CAE and controls (mean differences, 2.43; 95% CI, -1.15 to 6.02; I2, 50.60%; P = 0.18). While diabetes is a well-established risk factor for atherosclerotic coronary disease, our pooled evidence indicates its contribution to ectatic changes is limited and not associated with CAE.
Do Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio Reflect Coronary Artery Disease Severity Assessed by SYNTAX Score?: A Meta-Analysis.
Assayed A, Aburumman S, Abunemr I … +6 more , Salih ARF, Gruhonjic H, Minasyan A, Fabian D, Ledonio C, Prashad R
Cardiol Rev · 2026 Mar · PMID 41813624 · Publisher ↗
Coronary artery disease is a major global cause of morbidity and mortality, with systemic inflammation playing a central role in its pathophysiology. The SYNTAX (Synergy Between percutaneous coronary intervention With Ta...
Coronary artery disease is a major global cause of morbidity and mortality, with systemic inflammation playing a central role in its pathophysiology. The SYNTAX (Synergy Between percutaneous coronary intervention With Taxus and Cardiac Surgery) score is widely used to quantify the anatomical complexity of coronary lesions, but its invasiveness and cost limit routine application. Hematologic inflammatory indices such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been proposed as simple, inexpensive biomarkers that may reflect the presence and severity of coronary disease. This meta-analysis evaluated the association between NLR and PLR and angiographic complexity measured by the SYNTAX score. A systematic search of PubMed, MEDLINE, Cochrane, and CINAHL through May 2024 identified studies reporting correlations between NLR and/or PLR and SYNTAX scores in adults with coronary artery disease. Random-effects models using Fisher's z-transformation were applied to pool correlation coefficients. Heterogeneity was assessed using Cochran's Q, I2, and τ2. Subgroup analyses examined the effects of country, study design, and publication year, and meta-regression explored the influence of mean age and sex distribution. Publication bias was evaluated with funnel plots and Egger's regression. Fifteen studies involving 17,348 participants were included. NLR showed a significant positive correlation with SYNTAX score (r = 0.37; 95% CI, 0.28-0.45). PLR demonstrated a similar association (r = 0.38; 95% CI, 0.23-0.51). Heterogeneity was substantial for both indices. Stronger correlations were observed in Turkish cohorts, and increasing mean age was associated with larger effect sizes. No significant publication bias was detected. Both NLR and PLR correlate moderately with coronary lesion complexity and may provide accessible adjunctive markers for preprocedural risk stratification.
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