Cardiology In Review[JOURNAL]
Sun
200 papers
Lepodisiran: An Updated Review on a Novel and Emerging Lipoprotein (a) Lowering Agent.
Urina-Jassir M, Tong K, Stanisic A … +2 more , Frishman WH, Aronow WS
Cardiol Rev · 2026 Mar · PMID 41779052 · Publisher ↗
An elevated lipoprotein (a) concentration has been established as an independent risk factor for atherosclerotic cardiovascular disease (ASCVD). There is a high prevalence of elevated lipoprotein (a) in the general popul...
An elevated lipoprotein (a) concentration has been established as an independent risk factor for atherosclerotic cardiovascular disease (ASCVD). There is a high prevalence of elevated lipoprotein (a) in the general population, and given the significant burden of ASCVD, researchers have developed novel therapeutic drugs with a direct lipoprotein (a) reducing effect that are currently under investigation. One of these medications is lepodisiran, a small interfering RNA targeting lipoprotein (a). This drug has undergone safety assessment (in Phase 1 and 2 randomized control trials [RCTs]) as well as efficacy assessment (Phase 2 RCT, ALPACA Trial). A phase 3 RCT, ACCLAIM-Lp(a), is currently ongoing with the main purpose of assessing the effect on major cardiovascular events in patients with established ASCVD or at high cardiovascular risk. Herein, we present an updated review on this lipoprotein (a) lowering agent, including the results of the published clinical trials and the design of the ongoing phase 3 clinical trial.
Safety and Efficacy of Ticagrelor Versus Clopidogrel in Patients Aged 70 Years or Older With Acute Coronary Syndrome: A Systematic Review and Meta-Analysis.
Shaban M, Moazzam E, Yasir M … +15 more , Khan MM, Ikram J, Ali SH, Khan I, Jawad ZN, Khan A, Shah SW, Baroudi M, Awais M, Sawaira F, Hayat S, Mian UU, Khan S, Shakeel S, Ali A
Cardiol Rev · 2026 Mar · PMID 41779037 · Publisher ↗
Older adults with acute coronary syndrome (ACS) face high risks of recurrent ischemia, mortality, and bleeding complications from antiplatelet therapy. The safety and efficacy of ticagrelor versus clopidogrel in this vul...
Older adults with acute coronary syndrome (ACS) face high risks of recurrent ischemia, mortality, and bleeding complications from antiplatelet therapy. The safety and efficacy of ticagrelor versus clopidogrel in this vulnerable population remain uncertain due to their underrepresentation in clinical trials. We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase, and the Cochrane Library were searched from inception to October 2025 for randomized controlled trials and cohort studies comparing ticagrelor versus clopidogrel in ACS patients aged ≥70 years. Outcomes included myocardial infarction (MI), stroke, major bleeding, all-cause death, cardiovascular (CV) death, and the composite of CV death/MI/stroke. Hazard ratios (HRs) or risk ratios with 95% confidence intervals (CIs) were pooled using random-effects models. Heterogeneity was assessed via I2 statistics. Five studies (2 randomized controlled trials and 3 cohort studies) with 22,806 participants were included. Ticagrelor significantly reduced the risk of MI (HR 0.84, 95% CI 0.75-0.95, P = 0.004) and the composite endpoint of CV death, MI, or stroke (HR 0.85, 95% CI 0.74-0.98, P < 0.05). No significant differences were found between ticagrelor and clopidogrel in stroke incidence, major bleeding, or all-cause mortality. Heterogeneity was substantial for certain outcomes, particularly bleeding and mortality. In patients aged ≥70 years with ACS, ticagrelor was associated with reduced MI and composite ischemic events compared with clopidogrel, while no statistically significant differences in bleeding events or mortality were observed. However, substantial heterogeneity and reliance on observational data for some outcomes warrant cautious clinical interpretation.
Long COVID Myocarditis: Incidence, Mechanisms, Clinical Implications, and Management.
Dunde A, Maniyar P, Vora N … +7 more , Khan AA, Rajput J, Jain J, Agrawal SP, Maheta D, Frishman WH, Aronow WS
Cardiol Rev · 2026 Mar · PMID 41779029 · Publisher ↗
Long coronavirus disease (COVID) (post-acute sequelae of severe acute respiratory syndrome coronavirus 2 infection) is characterized by persistent or new health issues weeks or months after acute COVID-19. Cardiac involv...
Long coronavirus disease (COVID) (post-acute sequelae of severe acute respiratory syndrome coronavirus 2 infection) is characterized by persistent or new health issues weeks or months after acute COVID-19. Cardiac involvement, including myocarditis, is a notable complication that can occur even after an initially mild infection. To review current literature (2022-2025) on myocarditis in Long COVID, focusing on incidence, pathophysiological mechanisms, clinical presentation, diagnosis, management, prognosis, and future directions. Post-COVID myocarditis remains relatively uncommon but is significantly more frequent than pre-pandemic rates. Myocardial injury in Long COVID is hypothesized to result from multiple mechanisms: persistent viral antigen or RNA in cardiac tissue causing chronic immune activation, immune-mediated damage (including autoimmunity such as anti-heart antibodies), microvascular endothelial dysfunction with impaired perfusion, and maladaptive inflammatory responses. Patients may present with typical myocarditis symptoms (exertional chest pain, dyspnea, palpitations) or atypical features like exercise intolerance, orthostatic tachycardia, or unexplained fatigue. Management is supportive and guided by myocarditis severity: exercise restriction for 3-6 months in confirmed cases, guideline-directed heart failure therapy if ventricular dysfunction is present, anti-inflammatory or immunosuppressive therapy in specific scenarios (eg, corticosteroids in fulminant cases or overlapping multisystem inflammatory syndrome), and therapies targeting pericardial involvement (nonsteroidal anti-inflammatory drugs, colchicine) if present.
The Cardiac-Cerebral Reflex: Bridging Autonomic Dysfunction, Arrhythmia, and Sudden Cardiac Death.
Akram MB, Masood MA, Arif A … +4 more , Khan MA, Arif A, Khan AA, Arshad MMUD
Cardiol Rev · 2026 Mar · PMID 41779020 · Publisher ↗
The cardiac-cerebral reflex (CCR) is a bidirectional neural loop that continuously links cardiac sensory input with central autonomic control, and thereby governs heart rate, conduction, and myocardial excitability. Once...
The cardiac-cerebral reflex (CCR) is a bidirectional neural loop that continuously links cardiac sensory input with central autonomic control, and thereby governs heart rate, conduction, and myocardial excitability. Once thought of mainly as a homeostatic feedback mechanism, the CCR is now recognized as a key actor in the genesis of malignant arrhythmias and some forms of sudden cardiac death. This narrative review synthesizes current understanding of the CCR from cellular mechanisms to clinical syndromes. We highlight the Central Autonomic Network-with emphasis on the nucleus tractus solitarius and the insular cortex-and trace how aberrant autonomic signaling (excess sympathetic discharge, vagal imbalance) creates both the "spark" and the "substrate" for arrhythmogenesis. We review diagnostic approaches (heart rate variability, baroreflex testing, cardiac 123I-metaiodobenzylguanidine imaging, prolonged ECG/EEG monitoring), summarize therapeutic options with a focus on neuromodulation (cardiac sympathetic denervation, stellate blockade, vagus nerve stimulation), and propose practical steps for clinicians caring for patients in whom brain-heart interactions are central. Moving from a cardiocentric to a neurocardiac perspective can improve risk stratification and open new management avenues for arrhythmias that resist conventional approaches.
Renal Venous Hypertension and Kidney Dysfunction: Implications for Clinical Practice.
Flores J, Aggül B, Alvarado M … +3 more , Soliman D, Pena C, Nugent K
Cardiol Rev · 2026 Mar · PMID 41779019 · Publisher ↗
Renal venous hypertension (RVH) is a consequence of advanced cirrhosis, congestive heart failure, and other conditions that raise intra-abdominal pressure. Poor venous outflow increases pressure within the kidney, with s...
Renal venous hypertension (RVH) is a consequence of advanced cirrhosis, congestive heart failure, and other conditions that raise intra-abdominal pressure. Poor venous outflow increases pressure within the kidney, with subsequent increases in interstitial and tubular pressures leading to reductions in glomerular filtration rate and tubular function. This may present as oliguria, acute kidney injury, or progression of chronic kidney disease. Other conditions, like nutcracker syndrome, in which compression of the left renal vein produces hematuria, flank pain, and either pelvic congestion or varicocele, can also develop RVH. This vascular disorder can be identified with several imaging studies that allow clinicians to evaluate and prevent further complications in patients. Available diagnostic options include invasive approaches (renal venography with pressure measurement and intravascular ultrasound) and noninvasive imaging (Doppler ultrasound, computed tomography angiography, and magnetic resonance imaging). RVH is an important cause of renal dysfunction in systemic congestion; its presence leads to worse outcomes and complications in management. This review summarizes the epidemiology, pathophysiologic mechanisms, diagnostic strategies, and clinical scenarios in which RVH is encountered, emphasizing its relevance for cardiology, nephrology, and critical care practice.
Understanding Nicotine Addiction: Personalizing Therapy for Smoking Cessation.
Stein J, Minkin R, Parikh MA … +3 more , Rafiaa M, Frishman WH, Peterson SJ
Cardiol Rev · 2026 Mar · PMID 41769931 · Publisher ↗
Healthcare costs associated with smoking remain a persistent healthcare burden globally. Smoking is associated with increased mortality and morbidity. The addictive properties associated with smoking and the accompanying...
Healthcare costs associated with smoking remain a persistent healthcare burden globally. Smoking is associated with increased mortality and morbidity. The addictive properties associated with smoking and the accompanying withdrawal symptoms have created a difficult environment for achieving smoking cessation. Nicotine is ubiquitous within tobacco products and is the main driver of addiction. To reduce usage, research has been heavily devoted to the pharmacology of nicotine. Nicotinic acetylcholine receptors are the main targets of nicotine, and pharmacological cessation therapies have been designed to interfere with this interaction. There are 3 first-line therapies designed for smoking cessation in combination with behavioral support; these include nicotine replacement therapy, varenicline, and bupropion. Despite the availability of these agents, obstacles remain to achieving smoking cessation. These first-line therapies are expensive, have intolerable side effects for some individuals with nonuniform clinical benefits, and are not widely available. In response to this major challenge, there is an ongoing search for alternative therapies. The focus of this review is on cytisine, a smoking cessation aid widely used in eastern and central Europe as an additional tool for healthcare providers.
Overview of Best Practices and Complications in Hemodialysis Access.
Ye IB, Tan S, Jasinski PT … +1 more , Hines GL
Cardiol Rev · 2026 Feb · PMID 41738845 · Publisher ↗
End-stage renal disease and the number of patients relying on hemodialysis are increasing. Hemodialysis access, such as autogenous arteriovenous (AV) fistulas, prosthetic AV grafts, and tunneled catheters, is essential y...
End-stage renal disease and the number of patients relying on hemodialysis are increasing. Hemodialysis access, such as autogenous arteriovenous (AV) fistulas, prosthetic AV grafts, and tunneled catheters, is essential yet also a major source of morbidity. This focused narrative review summarizes the best practices for access planning. Complications after AV fistulas are reviewed, including stenosis, thrombosis, infection, central venous stenosis, steal syndrome, ischemic monomelic neuropathy, high-output cardiac failure, and aneurysmal degeneration. Multidisciplinary collaboration between nephrology, vascular surgery, and clinicians taking care of dialysis patients is essential to optimize long-term outcomes for patients dependent on hemodialysis. This review is intended for non-nephrologists taking care of dialysis-dependent patients in their practice.
Touch, Trust, and Truth; Why the Physical Exam Still Matters In the Age of AI: A Framework for the Physical Exam as a Bridge to Trust, Healing, and Increased Patient Adherence.
Whitford T, Goldberg C, Frishman WH … +1 more , Etienne M
Cardiol Rev · 2026 Feb · PMID 41738840 · Publisher ↗
We aim to demonstrate the therapeutic value of the physical examination beyond its diagnostic function and to examine theoretical pathways that contribute to patient-physician relationships and improve patient outcomes....
We aim to demonstrate the therapeutic value of the physical examination beyond its diagnostic function and to examine theoretical pathways that contribute to patient-physician relationships and improve patient outcomes. This paper examines the nondiagnostic, healing benefits of the physical examination by synthesizing evidence from studies in patient-clinician communication, physician-patient trust-building, and rapport development. We reviewed the literature on patient-physician communication, patient-centered care, and treatment adherence to construct a theoretical framework for understanding the potential therapeutic functions of the physical exam. Evidence indicates that effective physician-patient communication and trust-building behaviors are associated with improved patient outcomes. The physical examination provides opportunities to demonstrate such behaviors. Evidence suggests patients and physicians perceive therapeutic benefits from touch and physical examination during medical consultations. Patient acceptance of therapeutic touch is high, and physicians' experiences confirm that physical examination serves relationship-building functions beyond diagnosis. The physical examination represents an essential component of medical practice. Evidence supports its therapeutic value beyond diagnosis. Examinations offer opportunities for patient education and relationship-building through nonverbal communication, promoting rapport and improving health outcomes. Furthermore, the physical exam is a key strategic advantage that human beings have over artificial intelligence. Clinicians should perform physical examinations when clinically indicated and in accordance with the individual patient's preferences. When medical educators teach physical examination skills to students, they should acknowledge both the diagnostic and therapeutic benefits, as well as their importance in distinguishing physicians from artificial intelligence. Healthcare systems should allocate time for examination, recognizing that therapeutic value beyond diagnosis has empirical support.
Standards, Strategies, and Innovations in Cardiac Point-of-Care Ultrasound Education: A Scoping Review.
Liao J, Wahlberg KJ
Cardiol Rev · 2026 Feb · PMID 41738828 · Publisher ↗
Cardiac point-of-care-ultrasound (POCUS) is an invaluable diagnostic tool and is increasingly integrated into undergraduate and graduate medical education curricula. The purpose of this scoping review is to assess the li...
Cardiac point-of-care-ultrasound (POCUS) is an invaluable diagnostic tool and is increasingly integrated into undergraduate and graduate medical education curricula. The purpose of this scoping review is to assess the literature, identify educational gaps, potential remedies, and innovative teaching approaches for cardiac POCUS education. A scoping review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The literature search in PubMed, Cochrane, Education Resources Information Center, Embase, and Web of Science yielded 280 articles, of which 74 were included. Themes were identified, and education theory was applied to identify opportunities to improve cardiac POCUS education. Four primary themes were identified: challenges to POCUS education, application of technologies, innovative teaching methods, and assessment models. Themes were analyzed through the lens of cognitive load theory, and solutions were proposed to enhance cardiac POCUS education. Proposed solutions include recommendations that curriculum developers intentionally sequence task fidelity, incorporate worked examples, and structure progressive exposure to real-world complexity. In summary, cardiac POCUS is being widely integrated across the medical education continuum with numerous challenges inherent to the broad application of cardiac POCUS, diverse educational settings, resource limitations, difficulty translating POCUS skills to the bedside, and lack of universal standards and approaches to assessment. Application of cognitive load theory to cardiac POCUS curriculum development may enhance skill development and clinical translation.
VEGF Inhibitors in Hematologic Cancers and Hypertension/Cardiac Effects.
Thukral J, Kaur H, Sindhwani N … +7 more , Moudgil P, Chandani KU, Shah RK, Thukral N, Agrawal SP, Frishman WH, Aronow WS
Cardiol Rev · 2026 Feb · PMID 41738812 · Publisher ↗
The therapeutic landscape of hematologic malignancies has undergone a paradigm shift with the increasing incorporation of targeted therapies, including inhibitors of vascular endothelial growth factor (VEGF) signaling. W...
The therapeutic landscape of hematologic malignancies has undergone a paradigm shift with the increasing incorporation of targeted therapies, including inhibitors of vascular endothelial growth factor (VEGF) signaling. While VEGF-directed agents have historically been developed and deployed in solid tumors, their application in hematologic cancers-particularly multiple myeloma, select leukemias, and rare lymphomas-has expanded in investigational and clinical settings. VEGF is fundamental to angiogenesis, maintenance of endothelial integrity, and regulation of vascular tone. As a result, therapeutic inhibition of VEGF signaling is associated with a characteristic spectrum of cardiovascular adverse effects. These include hypertension, endothelial dysfunction, heart failure, thromboembolic complications, and renal injury, all of which present important clinical challenges in patients with hematologic malignancies. This population frequently has additional vulnerability due to factors such as cytopenias, preexisting renal impairment, and prior exposure to cardiotoxic anticancer therapies. This review aims to provide a cardio-oncology-oriented overview of VEGF biology, the range of VEGF-targeted agents used in hematologic cancers, and the underlying mechanisms driving their cardiovascular toxicities.
Oral Anticoagulation Versus No Anticoagulation in Patients of Atrial Fibrillation With Prior History of Intracranial Hemorrhage: A Meta-Analysis.
Jha M, Chahodiya D, Thaker L … +8 more , Matawala K, Siddiqui S, Jain H, Maheta D, Agrawal SP, Siddiq S, Frishman WH, Aronow WS
Cardiol Rev · 2026 Feb · PMID 41714901 · Publisher ↗
Atrial fibrillation is a major cause of ischemic stroke and systemic embolism. Oral anticoagulants (OACs) play a crucial role in preventing thromboembolic events in high-risk patients. However, evidence regarding initiat...
Atrial fibrillation is a major cause of ischemic stroke and systemic embolism. Oral anticoagulants (OACs) play a crucial role in preventing thromboembolic events in high-risk patients. However, evidence regarding initiation of OAC in patients with a prior intracranial hemorrhage (ICH) remains limited. We systematically searched PubMed, Scopus, and Cochrane Library for relevant articles published up to September 25, 2025, to evaluate the efficacy and safety of OACs in patients with atrial fibrillation and a history of ICH. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. A total of 9181 patients were included. OAC therapy significantly reduced ischemic stroke (RR: 0.38; 95% CI: 0.26-0.55; P < 0.00001) and ischemic stroke/systemic embolism (RR: 0.47; 95% CI: 0.36-0.61; P < 0.00001) when compared with no OAC therapy. OAC also reduced stroke-related mortality (RR: 0.55; 95% CI: 0.31-0.99; P = 0.04), all-cause mortality (RR: 0.68; 95% CI: 0.57-0.81; P < 0.0001), and major adverse cardiac events (RR: 0.69; 95% CI: 0.51-0.94; P = 0.02). However, its use was associated with a higher risk of major extracranial bleeding (RR: 1.70; 95% CI: 1.04-2.77; P = 0.03). There was no significant association between the use of OAC and recurrence of ICH (RR: 1.21; 95% CI: 0.69-2.13; P = 0.50). In conclusion, patients with previously documented ICH, OAC therapy substantially lowers the risk of ischemic stroke, systemic embolism, and major adverse cardiac events. There is no significant increase in intracranial bleeds with OAC. Prospective studies are needed to further refine the decision-making.
Advances in Predicting Postoperative Atrial Fibrillation: A Narrative Review of the Current Literature.
Feng R, Bae J, Elghobary N … +5 more , Gupta K, Vithlani K, Elsherbini A, Abu-Omar Y, El-Diasty M
Cardiol Rev · 2026 Feb · PMID 41711481 · Publisher ↗
Postoperative atrial fibrillation (POAF) is a common adverse event after cardiac surgery. It is associated with increased risk of both morbidity and mortality. Predictive modalities that stratify patients vulnerable to P...
Postoperative atrial fibrillation (POAF) is a common adverse event after cardiac surgery. It is associated with increased risk of both morbidity and mortality. Predictive modalities that stratify patients vulnerable to POAF have demonstrated both poor efficacy and conflicting results on their predictive ability. This narrative review aims to highlight the research on the existing technological POAF predictive modalities. Left atrium reduced reservoir and contractile strain seemed to be associated with an increased risk of POAF via echocardiography imaging. Likewise, textural features and index epicardial adipose tissue volume were associated with POAF risk determined using CT radiomics and magnetic resonance imaging, respectively. Several machine learning models including support vector machines, deep learning (DL), gradient boosted machine (GBM), logistic regression, and random forest (RF) exhibited effective risk stratification based on area under the curve (AUC). However, their predictive value is less established due to no single model consistently performing well. Our findings suggest that technological predictors of POAF involving the role of imaging and machine learning models may play an important role in predicting POAF risk among patients who underwent cardiac surgery. Integrating these novel modalities into existing means of risk stratification can potentially enhance postoperative outcomes. However, further studies involving wide-scale clinical trials are needed to support their usage.
Longitudinal Trends in Cardiac Arrest-Related Mortality in Patients With Chronic Obstructive Pulmonary Disease: A Retrospective U.S. Population-Based Study (1999-2023).
Anwar S, Jain H, Tariq MS … +9 more , Hassan A, Tariq U, Jannat A, Chaudhary A, Waqar H, Ahmed Z, Khan H, Ahmed R, Sharma UM
Cardiol Rev · 2026 Feb · PMID 41711465 · Publisher ↗
Sudden cardiac arrest (CA) is a leading cause of death in the United States, with coexisting chronic obstructive pulmonary disease (COPD) recognized as an independent risk factor. National trends in mortality among indiv...
Sudden cardiac arrest (CA) is a leading cause of death in the United States, with coexisting chronic obstructive pulmonary disease (COPD) recognized as an independent risk factor. National trends in mortality among individuals with both conditions remain unclear. Using Centers for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research (multiple cause-of-death data, we conducted a retrospective cross-sectional analysis of deaths with International Classification of Diseases, Tenth Revision codes for COPD (J41-J44) and CA (I46). Age-adjusted mortality rates (AAMRs) were calculated and stratified by race, sex, age group, census region, urbanization level, and place of death. Temporal trends were assessed using Joinpoint regression, reporting annual percent change (APC), and average annual percent change. From 1999 to 2023, a total of 853,773 deaths were recorded, with AAMRs declining from 35.48 to 22.77. The decline was steepest from 1999 to 2006 (APC: -2.77), followed by a more gradual reduction through 2021 (APC: -0.84), and a marked acceleration between 2021 and 2023 (APC: -5.52). Males consistently had higher AAMRs than females (35.41 vs 23.32). Racial disparities persisted, with non-Hispanic (NH) White (29.5) and NH Black individuals (28.16) experiencing the highest rates, followed by NH American Indians (26.17), Hispanics (22.2), and NH Asian/Pacific Islanders (17.82). Mortality was also highest in nonmetropolitan areas (31.37) and the Western region (39.68). Notably, home deaths increased following the coronavirus disease 2019 pandemic. Overall, CA-related mortality in individuals with COPD has declined over the past 25 years, with sharper reductions observed in the post-coronavirus disease period. Despite these improvements, persistent and widening disparities underscore the need for targeted interventions in high-risk populations.
Circulating Tumor DNA and Blood-Based Biomarkers for Predicting Cardiotoxicity in Cancer Therapy: Toward Precision Cardio-Oncology.
Thukral J, Moudgil P, Moudgil N … +9 more , Sindhwani N, Dhawan A, Shah RK, Kaur H, Thukral N, Chandani KU, Agrawal SP, Frishman WH, Aronow WS
Cardiol Rev · 2026 Feb · PMID 41711464 · Publisher ↗
Advances in cancer therapeutics have substantially improved survival across multiple malignancies but have concurrently increased the burden of cancer therapy-related cardiovascular toxicity, establishing cardio-oncology...
Advances in cancer therapeutics have substantially improved survival across multiple malignancies but have concurrently increased the burden of cancer therapy-related cardiovascular toxicity, establishing cardio-oncology as an essential discipline situated at the interface of oncology and cardiovascular medicine. Despite growing incorporation of cardiac imaging and circulating cardiac biomarkers into surveillance strategies, current approaches remain limited by modest specificity, heterogeneous risk profiles, and inconsistent translation into effective cardioprotective interventions. This review synthesizes contemporary evidence on the biological mechanisms underlying cancer therapy-related cardiovascular toxicity and critically evaluates the current role and limitations of established cardiac biomarkers, including high-sensitivity cardiac troponins and natriuretic peptides, in risk stratification and early injury detection. We further examine why many cardioprotective clinical trials have yielded neutral or modest results, highlighting signal dilution arising from low-risk populations, endpoint heterogeneity, and timing mismatches between injury biology and intervention. This review advances a precision cardio-oncology framework by integrating tumor-derived liquid biopsy platforms-such as circulating tumor DNA, tissue-specific cell-free DNA, and extracellular vesicles-with cardiac biomarkers to provide a biologically contextualized assessment of cardiovascular risk. Tumor-derived biomarkers may reflect treatment intensity, systemic inflammatory burden, and cardiotoxic susceptibility, thereby enhancing the interpretation of cardiac biomarker signals and refining patient selection for targeted cardioprotective strategies.
Incretin-Based Dual and Triple Agonists in Overweight or Obese Individuals: A Systematic Review and Meta-Analysis.
Chan ZH, Omar AS, Gill K … +11 more , Volucke G, Azhar MM, Haleem SM, Sia JE, Rahman OU, Ahmad M, Shahid N, Gardezi SA, Joseph KV, Behary Paray N, Zulfiqar E
Cardiol Rev · 2026 Feb · PMID 41711462 · Publisher ↗
Incretin-based dual and triple agonists have emerged as effective options for obesity management, offering enhanced weight loss through multi-receptor agonism. However, data on their efficacy and safety remain limited. W...
Incretin-based dual and triple agonists have emerged as effective options for obesity management, offering enhanced weight loss through multi-receptor agonism. However, data on their efficacy and safety remain limited. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of these emerging agents. A comprehensive literature search was conducted using PubMed, the Cochrane Library, and Google Scholar from inception to June 2025 to identify randomized controlled trials evaluating tirzepatide, retatrutide, or mazdutide in obese adults. Clinical outcomes were assessed using the random-effects model and pooled as mean differences (MDs) or risk ratios (RRs) with 95% confidence intervals (CIs). A total of 10 randomized controlled trials, including 3236 participants, were analyzed. Incretin polyagonists significantly reduced body weight compared to placebo (MD -11.47; 95% CI: -14.00 to -8.95). Significant reductions were also observed in waist circumference (MD -9.40; 95% CI: -11.91 to -6.89), glycated hemoglobin (MD -0.96; 95% CI: -1.16 to -0.75), and fasting plasma glucose (MD -26.89 mg/dL; 95% CI: -33.48 to -20.30). However, the use of dual and triple agonists was associated with a higher risk of any adverse events (AEs) (RR 1.13; 95% CI: 1.08-1.19), including gastrointestinal AEs (nausea, vomiting, diarrhea, constipation), AEs leading to withdrawal (RR 1.96; 95% CI: 1.17-3.30), and hypoglycemic episodes (RR 3.08; 95% CI: 1.61-5.89). No significant difference was found in serious AEs (RR 0.87; 95% CI: 0.65-1.14). In conclusion, incretin-based polyagonists were associated with significant weight reduction and improved metabolic outcomes compared to placebo.
The Alpha-Gal Syndrome and Hypersensitivity to Biomaterials: Understanding Xenoimmunity.
Sami N, Parikh MA, Mihatov N … +2 more , Frishman WH, Peterson SJ
Cardiol Rev · 2026 Feb · PMID 41703677 · Publisher ↗
Biomaterials derived from nonhuman mammals are increasingly used in cardiovascular interventions, yet xenoimmune responses to these materials can complicate these procedures. Xenoimmunity describes the immune response mo...
Biomaterials derived from nonhuman mammals are increasingly used in cardiovascular interventions, yet xenoimmune responses to these materials can complicate these procedures. Xenoimmunity describes the immune response mounted against foreign cells, tissues, or organs from different species. Alpha-gal syndrome, a tick-acquired IgE-mediated allergy to galactose-alpha-1,3-galactose, exemplifies this challenge. Patients face risk when exposed to porcine heparin, gelatin-based hemostatic agents, or bioprosthetic heart valves, with reactions ranging from delayed urticaria to immediate anaphylaxis. Alpha-gal sensitization has been linked to accelerated bioprosthetic valve degeneration and increased atherosclerotic plaque burden, suggesting that chronic immune activation may contribute to progressive cardiovascular disease. Cardiovascular hypersensitivity extends beyond alpha-gal syndrome. Drug-eluting stents with polymer coatings and metal alloys can trigger reactions that manifest as late thrombosis and restenosis. Cardiac implantable electronic devices cause hypersensitivity reactions in approximately 2% of recipients through titanium, nickel, and polymer components. Medications including protamine and iodinated contrast can precipitate life-threatening reactions through multiple immunologic pathways. Kounis syndrome and hypersensitivity myocarditis represent the most severe manifestations, where allergic responses directly cause acute coronary events or inflammatory cardiomyopathy. Recognition and prevention require coordinated clinical strategies. Systematic screening in tick-endemic regions helps identify at-risk patients before procedures. Multidisciplinary collaboration between cardiology and allergy specialists enables personalized prophylaxis tailored to sensitization profiles, while emerging diagnostic tools may distinguish benign antibody presence from clinically significant disease. Future progress depends on engineering cardiovascular devices that eliminate xenoantigenic epitopes and developing biomarkers that predict reaction risk. Clinicians must maintain awareness to recognize and prevent immune-mediated complications in susceptible patients.
Subcutaneous Furosemide, a Novel Therapy With Potential to Reduce Heart Failure Burden.
Kallash M, Frishman WH
Cardiol Rev · 2026 Feb · PMID 41703676 · Publisher ↗
Heart failure (HF) remains a global health challenge, with an urgent need to identify therapies that can reduce disease burden. A first-line agent in HF, furosemide, a loop diuretic, is regularly used for volume manageme...
Heart failure (HF) remains a global health challenge, with an urgent need to identify therapies that can reduce disease burden. A first-line agent in HF, furosemide, a loop diuretic, is regularly used for volume management in chronic HF patients. As maintenance therapy, oral furosemide is convenient to administer and efficacious. However, in decompensated HF with volume overload, oral furosemide becomes significantly less efficacious because of decreased absorption secondary to intestinal edema. Therefore, volume-overloaded HF patients are often hospitalized to facilitate administration of intravenous (IV) furosemide. While a subset of these patients may truly require hospitalization for stabilization and rapid diuresis with IV furosemide, a significant portion may not require hospitalization if an efficacious alternative to oral furosemide were available. Consequently, researchers have developed novel formulations of subcutaneous (SC) furosemide that can be self-administered as an alternative to oral furosemide. Numerous small randomized controlled trials demonstrated the safety and efficacy of SC furosemide, with equivalent diuresis compared with IV furosemide, resulting in recent Food and Drug Administration approval of multiple SC furosemide formulations. Despite approval, there remains a need for a large, randomized controlled trial to elucidate guidelines regarding the outpatient use of SC furosemide. Nevertheless, SC furosemide is not intended as a replacement for IV furosemide in patients requiring hospitalization for urgent diuresis due to complications related to volume overload. Instead, SC furosemide should serve as an alternative to oral furosemide in the outpatient setting in stable, volume-overloaded patients, thereby reducing the burden of unnecessary HF hospitalizations.
Efficacy and Safety of Selexipag in Pulmonary Hypertension: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Alowami M, Ch'ng BX, Babasola RO … +14 more , Tan CH, Koh MH, Harvard A, West B, Sohail S, Rahmaan A, Sutanto J, Afridi A, Ho S, Hassan EIE, Behary Paray N, Hashmi T, Alta'amreh M, Ahmed R
Cardiol Rev · 2026 Feb · PMID 41703674 · Publisher ↗
Selexipag, a selective prostacyclin receptor agonist, has been evaluated in randomized controlled trials (RCTs) for the treatment of pulmonary hypertension (PH), but results remain inconsistent. We performed an updated m...
Selexipag, a selective prostacyclin receptor agonist, has been evaluated in randomized controlled trials (RCTs) for the treatment of pulmonary hypertension (PH), but results remain inconsistent. We performed an updated meta-analysis to assess its efficacy and safety. PubMed, Embase, and Cochrane databases were searched systematically from September 2025. Eligible studies were RCTs comparing selexipag with placebo in adults with PH. The primary outcome was the change in pulmonary vascular resistance (PVR). Secondary outcomes included 6-minute walk distance (6MWD), all-cause mortality, hospitalization for worsening PH, N-terminal pro-brain natriuretic peptide (NT-proBNP), serious adverse events (SAEs), and treatment-related adverse events (AEs). A random-effects meta-analysis was conducted using RevMan. Six RCTs enrolling 1686 patients were included. Selexipag therapy was associated with a statistically significant reduction in NT-proBNP (WMD = -150.19 pg/mL; 95% confidence interval [CI] -185.88 to -114.51), hospitalization for worsening PH (odds ratio [OR] = 0.63; 95% CI, 0.48-0.84), and SAEs (OR = 0.47; 95% CI, 0.38-0.59). Selexipag did not significantly reduce PVR (WMD = - 68.0 dyn·s·cm-5; 95% CI, -145.9 to 9.9) or improve 6MWD (WMD = -1.05 m; 95% CI, - 4.6 to 2.5), or mortality (OR = 0.80; 95% CI, 0.44-1.45) as compared with placebo. Selexipag reduces hospitalizations, SAEs, and NT-proBNP levels but shows no clear benefit on PVR or 6MWD. Future trials are needed to confirm these findings.
Emerging and Established Pharmacotherapies for Smoking Cessation: A Review.
Huhulea EN, Frishman WH, Aronow WS
Cardiol Rev · 2026 Jan · PMID 41697002 · Publisher ↗
Tobacco use remains the leading preventable cause of death in the United States, with well-established links to cardiovascular morbidity and mortality. Despite the availability of pharmacologic and behavioral therapies,...
Tobacco use remains the leading preventable cause of death in the United States, with well-established links to cardiovascular morbidity and mortality. Despite the availability of pharmacologic and behavioral therapies, sustained smoking cessation remains a challenge for many individuals. This narrative review evaluates both established and emerging pharmacotherapies for smoking cessation, with a focus on recent evidence supporting cytisine and glucagon-like peptide-1 receptor agonists. Varenicline and combination nicotine replacement therapy continue to demonstrate the highest efficacy among first-line agents. Cytisine, a plant-derived partial nicotinic agonist, has shown effectiveness in early trials and may offer a favorable tolerability and cost profile. Glucagon-like peptide-1 receptor agonists, particularly exenatide, may reduce post-cessation weight gain and support abstinence in metabolically at-risk populations, though results require further validation. Behavioral interventions, including counseling and contingency management, enhance pharmacologic outcomes, particularly when combined. While current therapies improve quit rates, absolute abstinence remains modest, supporting the need for further research into combination regimens, precision medicine approaches, and long-term safety of emerging treatments.
Fibroblast Growth Factor-23 and Cardiovascular Disease in Patients With Chronic Kidney Disease.
Kim A, Parikh MA, Khalid H … +2 more , Frishman WH, Peterson SJ
Cardiol Rev · 2026 Feb · PMID 41680987 · Publisher ↗
Chronic kidney disease (CKD) is deemed one of the most potent factors that significantly increase the risk of cardiovascular morbidity and mortality. Yet, the magnitude of this excess risk cannot be explained solely by t...
Chronic kidney disease (CKD) is deemed one of the most potent factors that significantly increase the risk of cardiovascular morbidity and mortality. Yet, the magnitude of this excess risk cannot be explained solely by traditional cardiovascular risk factors, suggesting the presence of non hemodynamic, endocrine, and metabolic mechanisms linking renal dysfunction to cardiac disease. Fibroblast growth factor-23 (FGF-23), a bone-derived regulator of phosphate and vitamin D metabolism, rises early in CKD and has emerged as a key mediator of the cardiorenal-osteoendocrine axis. While physiological FGF-23 signaling through α-Klotho-dependent FGF receptor-1c (FGFR1c) maintains mineral homeostasis, pathological elevations in CKD promote Klotho-independent FGFR4 activation in the myocardium, leading to hypertrophy, fibrosis, diastolic dysfunction, and electrophysiological remodeling. Several cohort studies consistently demonstrate that elevated FGF-23 independently predicts left ventricular hypertrophy, heart failure, especially with preserved ejection fraction, atrial fibrillation, and mortality across CKD and even non-CKD populations, supporting its role as a biomarker of cardiovascular risk. However, clinical implementation is limited by assay heterogeneity, absence of standardized thresholds, and lack of definitive evidence that FGF-23-lowering interventions improve outcomes. This review examines FGF-23 physiology, mechanisms of pathological cardiac signaling in CKD, current clinical evidence, and current and emerging therapeutic strategies targeting the FGF-2-Klotho-FGFR axis.
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