Citations

Cardio-oncology has emerged as a critical discipline in modern medicine due to the growing population of cancer survivors and the increasing recognition of cardiovascular disease as a major cause of morbidity and mortality in this population. While there have been significant advances in chemotherapy such as advances in chemotherapy, targeted therapies, immunotherapies, and radiation therapy, these treatments are linked to a wide range of cardiovascular toxicities such as myocarditis, arrhythmias, and progressive fibrotic remodeling. These toxicities tend to be caused by interrelated and multifactorial cellular processes including endothelial damage, immunological dysregulation and mitochondrial dysfunction. Therefore, early diagnosis of subclinical harm using multimodal surveillance strategies integrating clinical risk assessment, specialized clinical imaging, and circulating biomarkers has replaced reactive care of overt cardiotoxicity in modern cardio-oncology. Echocardiographic techniques such as longitudinal strain, with the help of biomarker-guided surveillance of natriuretic peptides and cardiac troponins, have made the early detection of cardiac dysfunction more effective. However, the current prediction risk models are still constrained and limited by their dependence on static clinical variables and their partial integration of biological mechanisms. This review examines the current methods for risk stratification and surveillance throughout the cancer care continuum, including baseline assessment, monitoring during active therapy, and long-term survivorship surveillance. Future approaches for tailored cardiovascular care are also highlighted, including new advances in precision cardio-oncology such as multi-omics profiling, molecular biomarkers, artificial intelligence, and mechanism-guided preventative strategies. Therefore, advancing biologically informed and risk-adapted monitoring frameworks may enhance early diagnosis, maximize cardioprotective measures, and lower long-term cardiovascular consequences.

Importance Multiparametric magnetic resonance imaging (MRI), with or without prostate biopsy, has become the standard of care for diagnosing clinically significant prostate cancer. Resource capacity limits widespread adoption. Biparametric MRI, which omits the gadolinium contrast sequence, is a shorter and cheaper alternative offering time-saving capacity gains for health systems globally. Objective To assess whether biparametric MRI is noninferior to multiparametric MRI for diagnosis of clinically significant prostate cancer. Design, Setting, and Participants A prospective, multicenter, within-patient, noninferiority trial of biopsy-naive men from 22 centers (12 countries) with clinical suspicion of prostate cancer (elevated prostate-specific antigen [PSA] level and/or abnormal digital rectal examination findings) from April 2022 to September 2023, with the last follow-up conducted on December 3, 2024. Interventions Participants underwent multiparametric MRI, comprising T2-weighted, diffusion-weighted, and dynamic contrast–enhanced (DCE) sequences. Radiologists reported abbreviated biparametric MRI first (T2-weighted and diffusion-weighted), blinded to the DCE sequence. After unblinding, radiologists reported the full multiparametric MRI. Patients underwent a targeted biopsy with or without systematic biopsy if either biparametric MRI or multiparametric MRI was suggestive of clinically significant prostate cancer. Main outcomes and measures The primary outcome was the proportion of men with clinically significant prostate cancer. Secondary outcomes included the proportion of men with clinically insignificant cancer. The noninferiority margin was 5%. Results Of 555 men recruited, 490 were included for primary outcome analysis. Median age was 65 (IQR, 59-70) years and median PSA level was 5.6 (IQR, 4.4-8.0) ng/mL. The proportion of patients with abnormal digital rectal examination findings was 12.7%. Biparametric MRI was noninferior to multiparametric MRI, detecting clinically significant prostate cancer in 143 of 490 men (29.2%), compared with 145 of 490 men (29.6%) (difference, −0.4 [95% CI, −1.2 to 0.4] percentage points; P = .50). Biparametric MRI detected clinically insignificant cancer in 45 of 490 men (9.2%), compared with 47 of 490 men (9.6%) with the use of multiparametric MRI (difference, −0.4 [95% CI, −1.2 to 0.4] percentage points). Central quality control demonstrated that 99% of scans were of adequate diagnostic quality. Conclusion and relevance In men with suspected prostate cancer, provided image quality is adequate, an abbreviated biparametric MRI scan, with or without targeted biopsy, could become the new standard of care for prostate cancer diagnosis. With approximately 4 million prostate MRIs performed globally annually, adopting biparametric MRI could substantially increase scanner throughput and reduce costs worldwide. Trial registration ClinicalTrials.gov Identifier: NCT04571840

Cardiovascular–Kidney–Metabolic (CKM) syndrome symbolizes a single pathophysiologic entity including obesity, type 2 diabetes, chronic kidney disease, and cardiovascular disease. These conditions altogether accelerate adverse outcomes when they coexist. Recent evidence has shown that the function of glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium–glucose cotransporter-2 inhibitors (SGLT2i) alleviate stress on multiple organs. SGLT2i has been demonstrated to benefit heart failure, hemodynamic regulation, and renal protection while GLP-1RA on the other hand has been shown to demonstrate a strong impact on glycemic management, weight loss, and atherosclerotic cardiovascular disease. This review will aim to understand and evaluate the mechanistic rationalization, clinical evidence, and the potential therapeutic treatment of SGLT2 inhibitors and GLP-1 receptor agonists to treat individuals who have CKM syndrome. This analysis also assesses whether combination therapy can be a synergistic approach that may benefit patients but is still underutilized because of the lack of clear guidelines, the associated costs, and disparities in accessibility. Therefore, in this review, we will be discussing the combination therapy’s additive and synergistic effects, current recommendations and clinical evidence, and mechanistic insights of these GLT2 inhibitors and GLP-1 receptor agonists in CKM syndrome patients. Overall, early and combination usage of GLP-1RA and SGLT2i may be essential to demonstrating a significant shift in modern cardiometabolic therapy toward patient-centered care.

e24020 Background: Transcatheter aortic valve replacement (TAVR) is a widely adopted treatment for severe aortic stenosis, but outcomes in cancer survivors with prior chest radiation therapy (C-XRT) remain uncertain. This study compares the clinical outcomes of TAVR between patients with a history of C-XRT and those without prior radiation exposure (control group). Methods: Patients with prior chest radiation therapy (C-XRT) were compared to a control group without radiation exposure to evaluate key clinical endpoints. For each endpoint, odds ratios (OR) and 95% confidence intervals (CI) were determined, and heterogeneity was analyzed using the I² statistic. A p-value of <0.05 was considered statistically significant. Results: Nine studies were included in the meta-analysis, encompassing 3083 C-XRT and 8891 control patients. Patients with prior C-XRT showed significantly higher long-term mortality (OR 1.84, 95% CI [1.08, 3.13], p=0.02) compared to controls. Other outcomes, including access-related vascular complications, Acute Kidney Injury, Congestive heart failure, major bleeding, need for pacemaker, short-term mortality, and stroke, did not demonstrate significant differences between the groups. Conclusions: Cancer survivors with prior chest radiation therapy undergoing TAVR may experience higher long-term mortality compared to patients without radiation exposure. However, no significant differences were observed in other major outcomes. These findings suggest that while TAVR is a viable treatment for C-XRT patients, long-term risks require further investigation to optimize patient selection and management strategies. Outcomes. Outcome OR 95% Confidence Interval P value Access related vascular complications 1.12 [0.85, 1.48] 0.43 Acute kidney injury 0.54 [0.20, 1.50] 0.24 Congestive heart failure 1.38 [0.88, 2.17] 0.16 Long term mortality 1.84 [1.08, 3.13] 0.02 Major bleeding 0.96 [0.78, 1.17] 0.67 Need for pacemaker 1.05 [0.88, 1.26] 0.57 Short term mortality 1.66 [0.97, 2.84] 0.06 Stroke 1.25 [0.74, 2.11] 0.39

e24024 Background: Patients with active cancer undergoing trans catheter aortic valvular replacement (TAVR) face a higher risk of adverse outcomes due to the interplay between cancer and cardiovascular disease. Although TAVR is increasingly used in high-risk populations, data on outcomes for these patients remain limited. This systematic review and meta-analysis aim to evaluate the clinical outcomes associated with TAVR in patients with active cancer compared to non-cancer controls, providing insights to inform clinical decision-making in this unique group. Methods: A systematic search of major databases (PubMed, Embase, OVID, Web of Science, Scopus) was conducted to identify studies comparing clinical outcomes of TAVR between patients with active cancer and those without cancer. Key outcomes included measures of mortality, procedural complications, and post-procedure adverse events. The Mantel-Haenszel method was used for pooled analysis, applying random-effects or fixed-effects modeling based on heterogeneity assessed by Higgins I². Statistical significance was set at a p-value < 0.05. Results: Twelve studies involving 5,73,192 patients (67,684 active cancer, 505508 control) were included. Patients with active cancer undergoing TAVR have significantly higher risks of short-term mortality (OR 1.31, 95% CI [1.15, 1.49], p < 0.0001), long-term mortality (OR 2.24, 95% CI [1.85, 2.70], p < 0.0001), and major bleeding complications (OR 1.80, 95% CI [1.68, 1.92], p < 0.0001). There were no statistically significant differences in cardiovascular mortality (OR 1.33, 95% CI [0.94, 1.89], p = 0.11), myocardial infarction (OR 1.60, 95% CI [0.82, 3.11], p = 0.17), stroke (OR 0.61, 95% CI [0.28, 1.35], p = 0.22), AKI (OR 0.92, 95% CI [0.49, 1.73], p = 0.80), or the need for permanent pacemaker implantation (OR 1.12, 95% CI [0.85, 1.48], p = 0.42). Conclusions: Patients with active cancer undergoing TAVR face significantly higher risks of mortality and major bleeding compared to non-cancer controls. However, the risks of cardiovascular mortality, MI, stroke, AKI, and the need for permanent pacemaker implantation are comparable to those of non-cancer controls. Careful risk assessment and management are crucial for optimizing outcomes in this vulnerable population, and further studies are needed to refine treatment strategies. Odds ratios of all outcomes. Outcomes OR Confidence Interval (95% CI) p-value Short term mortality 1.31 [1.15, 1.49] < 0.0001 Long term mortality 2.24 [1.85, 2.70] < 0.00001 Major bleeding 1.8 [1.68, 1.92] < 0.00001 Cardiovascular mortality 1.33 [0.94, 1.89] 0.11 Myocardial Infarction 1.6 [0.82, 3.11] 0.17 Stroke 0.61 [0.28, 1.35] 0.22 Acute Kidney Injury 0.92 [0.49, 1.73] 0.8 Need for permanent pacemaker implantation 1.12 [0.85, 1.48] 0.42

Abstract This retrospective analysis aimed to provide evidence-based risk stratification of TP53-mutated (TP53mut) myeloid neoplasms (MNs). Of 580 MNs harboring TP53mut with variant allele frequency (VAF) ≥2%, 219 (37.8%), 194 (33.4%), 92 (15.9%), and 75 (12.9%) were classified as acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) with low blasts (MDS-LB), MDS with excess blasts (MDS-EB)-2, and -EB1 according to the revised fourth edition of the World Health Organization (WHO) classification, respectively. Hierarchical analysis identified the following 4 risk groups with distinct survival: (1) MDS-LB, (2) MDS-EB1/EB2/AML VAF &lt;10%, (3) MDS-EB1/EB2 VAF ≥10%, and (4) AML VAF ≥10%. We next evaluated the impact of allelic status, VAF, and complex karyotype (CK). In our cohort, the significance of biallelic status was limited to MDS with &lt;5% blasts and not for blasts 5% to 9%, as proposed by the International Consensus Classification (ICC), or 5% to 19%, as proposed by the fifth edition of the WHO (WHO-5). MDS-EB1 and -EB2 with VAF ≥10% had comparable survival (9.6 vs 7.2 months; P = .12), regardless of allelic status. Contrary to the ICC proposal, MDS-EB1/EB2 with VAF &lt;10% and CK had poor survival compared with those without CK, comparable to MDS-EB1/EB2 with VAF ≥10% (5.6 vs 26.2 vs 6.3 months; P = .003). Survival of TP53mut AML was poor (median 3.9 months) regardless of allelic/CK status. Thus, using ICC or WHO-5 may underestimate prognosis of MDS with blasts 5% to 19% and 5% to 9%, respectively. Collectively, the hierarchical model acknowledges poor survival of 91.9% TP53mut MDS and AML compared with 36.5% and 80.7% by WHO-5 and ICC, respectively.