Risk Stratification Strategies Research Articles

The association between triglyceride-glucose index and related parameters and risk of cardiovascular disease in American adults under different glucose metabolic states.

Cardiovascular disease (CVD) encompasses an array of cardiac and vascular disorders, posing a significant threat to global health. It remains unclear whether there exists an association between triglyceride-glucose index (TyG) and its derived indices and the incidence of cardiovascular disease, and in particular, the strength of the association in populations with different glucose metabolisms is not known. Data extracted from the National Health and Nutrition Examination Survey (NHANES) covering the period from 1999 to 2020, involving a cohort of 14,545 participants, were leveraged for the analysis. Statistical assessments were executed utilizing R software, employing multivariable logistic regression models to scrutinize the correlation between TyG and its associated parameters with the incidence of cardiovascular disease across diverse glucose metabolism categories. Interaction analyses and restricted cubic splines were applied to evaluate potential heterogeneity in associations and investigate the link between TyG and its derivatives with the occurrence of cardiovascular disease. Furthermore, receiver operating characteristic curves were constructed to evaluate the extent of variability in the predictive performance of TyG and its derived parameters for cardiovascular disease across distinct glucose metabolic statuses. This study found that TyG and its related parameters were differentially associated with the occurrence of cardiovascular disease in different glucose metabolic states. Curvilinear correlations were found between TyG in the IFG population and TyG-WC, TyG-BMI, and TyG-WHtR in the impaired glucose tolerance (IGT) population with the occurrence of cardiovascular disease. In addition, the introduction of TyG and its derived parameters into the classical Framingham cardiovascular risk model improved the predictive performance in different glucose metabolism populations. Among them, the introduction of TyG-WHtR in the normal glucose tolerance (NGT), impaired fasting glucose (IFG), IFG & IGT and diabetes groups and TyG in the IGT group maximized the predictive power. The findings provide new insights into the relationship between the TyG index and its derived parameters in different glucose metabolic states and the risk of cardiovascular disease, offering important reference value for future clinical practice and research. The study highlights the potential for improved risk stratification and prevention strategies based on TyG and its derived parameters.

Abstract PO5-15-11: A Novel Biosignature to Predict Radiation Therapy Response in Early-Stage Invasive Breast Cancer Treated with Breast-Conserving Surgery

Abstract Introduction: Radiation therapy (RT) is a standard component of treatment for most patients with early-stage, hormone receptor-positive, invasive breast cancer (BC) following breast-conserving surgery (BCS). RT recommendations are primarily based on clinicopathologic (CP) factors, such as tumor size, nodal status, and histological grade. While these factors provide prognostic information, their ability to accurately identify patients at a higher risk of ipsilateral breast recurrence (IBR) or those who will significantly benefit from RT is unclear. Therefore, incorporation of additional predictive markers beyond CP factors is warranted and there remains a need to refine the selection criteria for patients who will derive the greatest benefit from RT. In this study, we aimed to explore the role of immune and metabolic signaling axes as potential predictive markers for RT response in hormone receptor-positive breast cancer patients. Methods: A cohort of 939 women from Sweden were diagnosed with BC between 1987 and 2004. A subset of 471 patients was diagnosed with T1-T2N0M0 BC and underwent BCS with negative margins. Patients were treated with BCS plus/minus RT (median dose 50Gy) based upon physician preference. Biomarkers were assayed in formalin-fixed paraffin-embedded tissue micro arrays using multiplex immunofluorescence and multi-spectral imaging in a CLIA lab (Laguna Hills, CA). Immune and metabolic axes were defined employing biomarkers and used to classify patients into three risk groups: 1) Low Risk (lower baseline risk and no RT benefit), 2) Elevated Risk (higher baseline risk and significant RT benefit), and 3) Residual Risk (higher baseline risk and suboptimal RT benefit). Risk groups were analyzed for IBR rate using Kaplan-Meier and Cox proportional hazards analyses. Risk group prognosis and RT prediction was assessed for RT-risk group interaction in multivariable analysis, adjusting for CP factors. Results: Among the patients with complete biomarker data, 261 were hormone receptor-positive, and had a median follow-up of 140 months. Median age was 62 years (28-88 years), and median tumor size was 1.1 cm (0.1-4 cm). Some patients (21%) received endocrine therapy (ET), and most (76%) received RT, with 79% of patients who received ET also receiving RT. In the overall population, RT following BCS was associated with a reduction in HR for recurrence (HR=0.3, 95%CI [0.1, 0.5], p< 0.001). Patients classified as Low Risk (41%) did not have a significant benefit from RT (HR=0.9, 95%CI [0.1, 8.3], p=0.95) in multivariable analysis adjusted for CP factors. For patients who were classified as Elevated Risk (31%), multivariable analysis showed a higher IBR rate without RT (HR=5.7, 95%CI [1.3, 25.1], p< 0.021) relative to the Low Risk group who had a significant benefit from RT (HR=0.1, 95%CI [0.02, 0.2], p< 0.001). Patients classified into the Residual Risk group (28%) had no significant reduction from RT (HR=0.7, 95%CI [0.2, 2.0], p=0.61). However, in multivariable analysis adjusted for CP factors, patients treated with RT in the Residual Risk group had higher IBR rates (HR=3.7, 95%CI [1.6, 8.7], p=0.0026) compared to RT-treated patients in other risk groups. The biosignature was predictive for RT benefit in multivariable analysis adjusted for CP factors (p-interaction < 0.001). Conclusions:The biosignature used in this study demonstrated the potential to identify patients who may derive limited benefit from RT, allowing for tailored therapeutic approaches. These findings underscore the importance of individualized treatment decisions based on risk stratification. Further clinical validation and refinement of risk stratification strategies are warranted to optimize outcomes in hormone receptor-positive, BC patients undergoing BCS. Citation Format: Troy Bremer, Karuna Mittal, Chirag Shah, Frank Vicini, Steven Shivers, Charlotta Wadsten. A Novel Biosignature to Predict Radiation Therapy Response in Early-Stage Invasive Breast Cancer Treated with Breast-Conserving Surgery [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-15-11.

Abstract ED01-01: Optimizing endocrine therapy in premenopausal women

Abstract Premenopausal women with early-stage hormone receptor (HR)-positive breast cancer are candidates for adjuvant endocrine therapy and have several treatment options. The clinical team should assess an individual woman’s risk of recurrence, estimate benefits from specific endocrine manipulations, and consider co-morbidities, adverse event profile and host factors. Risk stratification strategies including clinic-pathologic features, genomic assays and composite scores can guide recommendations regarding type and duration of endocrine therapy, in particular in node-negative disease. Adjuvant tamoxifen for 5 to 10 years significantly reduces breast cancer recurrence and death. Premenopausal women who are at high risk of recurrence benefit from ovarian function suppression (OFS) with tamoxifen or an aromatase inhibitor for 5 years. Those include women with high-risk clinico-pathological features and younger age, and for whom chemotherapy is commonly recommended. There are currently no available data regarding the use of extended OFS beyond 5 years. Newer data support the addition of CDK 4/6 inhibitors to endocrine therapy in women with high-risk disease. Endocrine therpay is associated with frequent bothersome and few significant side effects that can negatively impact quality of life and adherence to treatment. Clinicians must carefully weigh the benefits associated with specific endocrine therapies, and possible short- and long-term side effects to individualize therapy, and to consider interventions to enhance adherence. Citation Format: V. Stearns. Optimizing endocrine therapy in premenopausal women [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr ED01-01.

Serial Cardiac Magnetic Resonance Imaging in Patients with Mitral Valve Prolapse-A Single-Center Retrospective Registry.

Background: Mitral valve prolapse (MVP) and mitral annular disjunction (MAD) are common valvular abnormalities that have been associated with ventricular arrhythmias (VA). Cardiac magnetic resonance imaging (CMR) has a key role in risk stratification of VA, including assessment of late gadolinium enhancement (LGE). Methods: Single-center retrospective analysis of patients with MVP or MAD who had >1 CMR and >1 24 h Holter registration available. Data are presented in detail, including evolution of VA and presence of LGE over time. Results: A total of twelve patients had repeated CMR and Holter registrations available, of which in four (33%) patients, it was conducted before and after minimal invasive mitral valve repair (MVR). After a median of 4.7 years, four out of eight (50%) patients without surgical intervention had new areas of LGE. New LGE was observed in the papillary muscles and the mid to basal inferolateral wall. In four patients, presenting with syncope or high-risk non-sustained ventricular tachycardia (VT), programmed ventricular stimulation was performed and in two (50%), sustained monomorphic VT was easily inducible. In two patients who underwent MVR, new LGE was observed in the basal inferolateral wall of which one presented with an increased burden of VA. Conclusions: In patients with MVP and MAD, repeat CMR may show new LGE in a small subset of patients, even shortly after MVR. A subgroup of patients who presented with an increase in VA burden showed new LGE upon repeat CMR. VA in patients with MVP and MAD are part of a heterogeneous spectrum that requires further investigation to establish risk stratification strategies.

Postoperative myocardial injury after major head and neck cancer surgery

Background/objective: This narrative review aims to assess the causes and evaluate the scientific evidence concerning the increased risk of postoperative myocardial infarction (PMI) in patients undergoing major head and neck surgery. Method: A comprehensive review of literature was conducted and findings from clinical trials, meta-analysis as well as observational studies were incorporated to explore the risk factors associated with PMI after a major head and neck surgery. Preoperative risk factors, appropriate diagnostic plans, biomarkers, risk stratification strategies, and treatment options were also assessed. Result: The review highlights that patients undergoing head and neck surgery are at a significant risk of developing PMI primarily due to surgical trauma, anesthesia, and the extensive nature of head and neck surgeries. However, pre-existing conditions like renal insufficiency, cerebrovascular diseases, and diabetes may also exacerbate this risk. Moreover, ECG and regular observation of troponin has proven to be successful in detecting PMI, which can be easily masked due to its ambiguous symptoms in postoperative patients that are receiving pain reducing medications. Once diagnosed, PMI is treated with standard medication for myocardial infarction, however, more emphasis has been put on its timely diagnosis through routine troponin testing. Conclusion: Head and neck cancers are prevalent in developing nations such as Pakistan where the use of tobacco is widespread. As a result of such aggressive cancer, patients may undergo surgery, which places them at a risk of developing PMI. This can be avoided through routine troponin testing which still requires further research on localized patient population considering the physiologic differences.

Proposal of a Modified Classification of Hypertensive Crises: Urgency, Impending Emergency, and Emergency

Abstract: Systemic arterial hypertension (HTN) is the main cause of morbidity and mortality, and HTN crises contribute significantly to an unfavourable clinical course. For decades, HTN crises have been dichotomized into hypertensive emergency (HTN-E) and hypertensive urgency (HTN-U). The main difference between the two is the presence of acute hypertension-mediated organ damage (HMOD) – if HMOD is present, HTN crisis is HTN-E; if not, it is HTN-U. Patients with HTN-E are in a life-threatening situation. They are hospitalized and receive antihypertensive drugs intravenously (IV). On the other hand, patients with HTN-U are usually not hospitalized and receive their antihypertensives orally. We suggest a modification of the current risk stratification scheme for patients with HTN crises. The new category would be the intermediate risk group, more precisely the ‘impending HTN-E’ group, with a higher risk in comparison to HTN-U and a lower risk than HTN-E. ‘Impending HMOD’ means that HMOD has not occurred (yet), and the prognosis is, therefore, better than in patients with ongoing HMOD. There are three main reasons to classify patients as having impending HTN-E: excessively elevated BP, high-risk comorbidities, and ongoing bleeding/high bleeding risk. Their combinations are probable. This approach may enable us to prevent some HTNEs by avoiding acute HMOD using a timely blood pressure treatment. This treatment should be prompt but controlled.

Effects of the stress hyperglycemia ratio on long-term mortality in patients with triple-vessel disease and acute coronary syndrome

AimsRisk assessment for triple-vessel disease (TVD) remain challenging. Stress hyperglycemia represents the regulation of glucose metabolism in response to stress, and stress hyperglycemia ratio (SHR) is recently found to reflect true acute hyperglycemic status. This study aimed to evaluate the prognostic value of SHR and its role in risk stratification in TVD patients with acute coronary syndrome (ACS).MethodsA total of 3812 TVD patients with ACS with available baseline SHR measurement were enrolled from two independent centers. The endpoint was cardiovascular mortality. Cox regression was used to evaluate the association between SHR and cardiovascular mortality. The SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) II (SSII) was used as the reference model in the model improvement analysis.ResultsDuring a median follow-up of 5.1 years, 219 (5.8%) TVD patients with ACS suffered cardiovascular mortality. TVD patients with ACS with high SHR had an increased risk of cardiovascular mortality after robust adjustment for confounding (high vs. median SHR: adjusted hazard ratio 1.809, 95% confidence interval 1.160–2.822, P = 0.009), which was fitted as a J-shaped pattern. The prognostic value of the SHR was found exclusively among patients with diabetes instead of those without diabetes. Moreover, addition of SHR improved the reclassification abilities of the SSII model for predicting cardiovascular mortality in TVD patients with ACS.ConclusionsThe high level of SHR is associated with the long-term risk of cardiovascular mortality in TVD patients with ACS, and is confirmed to have incremental prediction value beyond standard SSII. Assessment of SHR may help to improve the risk stratification strategy in TVD patients who are under acute stress.

Surveillance of non-muscle-invasive bladder cancer with blue-light cystoscopy: a meta-analysis.

To compare the value of flexible blue-light cystoscopy (BLC) vs flexible white-light cystoscopy (WLC) in the surveillance setting of non-muscle-invasive bladder cancer (NMIBC). All major databases were searched for articles published before May 2023 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The primary outcome was the accuracy of flexible BLC vs WLC in detecting bladder cancer recurrence among suspicious bladder lesions. A total of 10 articles, comprising 1634 patients, were deemed eligible for the quantitative synthesis. In the meta-analysis focusing on the detection of disease recurrence, there was no difference between flexible BLC and WLC (odds ratio [OR] 1.08, 95% confidence interval [CI] 0.82-1.41)]; the risk difference (RD) showed 1% of flexible BLC, corresponding to a number needed to treat (NNT) of 100. In the subgroup meta-analysis of detection of carcinoma in situ (CIS) only, there was again no significant difference between flexible BLC and WLC (OR 1.19, 95% CI 0.82-1.69), BLC was associated with a RD of 2% (NNT = 50). The positive predictive values for flexible BLC and WLC in detecting all types of recurrence were 72% and 66%, respectively, and for CIS they were 39% and 29%, respectively. Surveillance of NMIBC with flexible BLC could detect more suspicious lesions and consequently more tumour recurrences compared to flexible WLC, with a increase in the rate of false positives leading to overtreatment. A total of 100 and 50 flexible BLC procedures would need to be performed to find on additional tumor and CIS recurences, respectively. A risk-stratified strategy for patient selection could be considered when using flexible BLC for the surveillance of NMIBC patients.

Is Low-free Triiodothyronine (fT3) Associated with Increased Morbidity in Patients Admitted to Coronary Care Units?

The effects of thyroid hormone on patients hospitalized in coronary intensive care units are still controversial. We retrospectively examined thyroid hormone levels and their impact on cardiovascular morbidity in patients admitted to coronary intensive care units. A total of 208 (Female/Male; 47.1%/52.9%) patients without any history of thyroid disease were enrolled and screened. Patients with specific heart disease and existing thyroid hormone parameters were included in the study. Low triiodothyronine syndrome is characterized by reduced serum total or free T3 (fT3) concentrations in normal free T4 (fT4) and TSH levels. The common diagnosis of the patients in the coronary care unit is acute coronary syndrome (n=59, 28.2 %) and heart failure (n=46, 23.3%). Patients were divided into two groups according to left ventricular ejection fraction percentages (LVEF ≤39% vs LVEF ≥40%). Plasma fT3 levels were significantly correlated with low LVEF (≤39%) (p =0.002). fT3 (r=-0.183, p =0.013) and hospitalization etiology (r=-0.161, p =0.023) were also the most critical parameters affecting the length of hospitalization. Low fT3 was associated with reduced ejection fraction and prolonged hospitalization, which may lead to potential morbidities in HF patients, which may be useful in risk stratification and treatment strategies.

Cardiovascular Risk in Young Patients Diagnosed With Obstructive Sleep Apnea.

In older adults, obstructive sleep apnea (OSA) has been associated with several cardiovascular complications. Whether young patients diagnosed with OSA also are at higher risk of developing subsequent cardiovascular disease is uncertain. We aimed to estimate the risk of developing an incident cardiovascular event among young patients diagnosed with OSA. We linked nationwide Danish health registries to identify a cohort of patients aged ≤50 years with OSA using data from 2010 through 2018. Cases without OSA from the general population were matched as controls (1:5). The main outcome was any cardiovascular event (including hypertension, diabetes, atrial fibrillation, ischemic heart disease, ischemic stroke, heart failure, and venous thromboembolism). All-cause mortality was a secondary outcome. The study included 20 240 patients aged ≤50 years with OSA (19.6% female; mean±SD age 39.9±7.7 years) and 80 314 controls. After 5-year follow-up, 31.8% of the patients with OSA developed any cardiovascular event compared with 16.5% of the controls, with a corresponding relative risk (RR) of 1.96 (95% CI, 1.90-2.02). At 5-year follow-up, 27.3% of patients with OSA developed incident hypertension compared with 15.0% of the controls (RR, 1.84 [95% CI, 1.78-1.90]). Incident diabetes occurred in 6.8% of the patients with OSA and 1.4% of controls (RR, 5.05 [95% CI, 4.60-5.54]). Similar to older adults, young adults with OSA demonstrate increased risk of developing cardiovascular events. To prevent cardiovascular disease progression, accumulation of cardiovascular risk factors, and mortality, risk stratification and prevention strategies should be considered for these patients.

Risks of malignancy in the major nongynecologic cytopathology reporting systems: Critiques and discussions.

The ever-increasing popularity of standardized systems for reporting cytopathology has led in part to much attention to and importance of the risk stratification schemes, especially the risks of malignancy (ROMs), which are associated with the different diagnostic categories and upon which recommendations for clinical management are based. However, it is well known that the ROM calculations are based on retrospective reviews of the existing literature, representing a heterogeneous patient population, and are plagued by significant biases and variations. Statistically, the ROM represents the post-test probability of malignancy, which changes with the test result and with the prevalence of malignancy (or pretest probability) in an individual practice setting and individual patient presentation. Therefore, the clinical utility of the ROM is questioned and likely needs a second look in the nongynecologic cytopathology reporting systems. In this communication, the authors discuss the status of the ROM estimates according to the most commonly used nongynecologic reporting systems, including for thyroid, salivary glands, and others, highlighting similarities and differences with a focus on the limitations of ROM estimates and their application in clinical practice.

Abstract 2313: Multi-modal deep learning to predict cancer outcomes by integrating radiology and pathology images

Abstract Purpose: Cancer patients routinely undergo radiologic and pathologic evaluation for their diagnostic workup. These data modalities represent a valuable and readily available resource for developing new prognostic tools. Given their vast difference in spatial scales, effective methods to integrate the two modalities are currently lacking. Here, we aim to develop a multi-modal approach to integrate radiology and pathology images for predicting outcomes in cancer patients. Methods: We propose a multi-modal weakly-supervised deep learning framework to integrate radiology and pathology images for survival prediction. We first extract multi-scale features from whole-slide H&E-stained pathology images to characterize cellular and tissue phenotypes as well as spatial cellular organization. We then build a hierarchical co-attention transformer to effectively learn the multi-modal interactions between radiology and pathology image features. Finally, a multimodal risk score is derived by combining complementary information from two images modalities and clinical data for predicting outcome. We evaluate our approach in lung, gastric, and brain cancers with matched radiology and pathology images and clinical data available, each with separate training and external validation cohorts. Results: The multi-modal deep learning models achieved a reasonably high accuracy for predicting survival outcomes in the external validation cohorts (C-index range: 0.72-0.75 across three cancer types). The multi-modal prognostic models significantly improved upon single-modal approach based on radiology or pathology images or clinical data alone (C-index range: 0.53-0.71, P<0.01). The multi-modal deep learning models were significantly associated with disease-free survival and overall survival (hazard ratio range: 3.23-4.46, P<0.0001). In multivariable analyses, the models remained an independent prognostic factor (P<0.01) after adjusting for clinicopathological variables including cancer stage and tumor differentiation. Conclusions: The proposed multi-modal deep learning approach outperforms traditional methods for predicting survival outcomes by leveraging routinely available radiology and pathology images. With further independent validation, this may afford a promising approach to improve risk stratification and better inform treatment strategies for cancer patients. Citation Format: Zhe Li, Yuming Jiang, Ruijiang Li. Multi-modal deep learning to predict cancer outcomes by integrating radiology and pathology images [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2313.

Abstract 6198: TP53 mutational clusters stratify the Li-Fraumeni syndrome spectrum

Abstract Li-Fraumeni syndrome (LFS) is a highly penetrant cancer predisposition disorder caused by germline variants in the TP53 tumor suppressor gene. LFS has recently been redefined as a ‘spectrum’ disorder to reflect the highly variable cancer types with largely unpredictable ages-of-onset and disease severity. The broad functional gradient associated with different TP53 variants is thought to contribute to LFS heterogeneity, although it is still poorly understood and there is an unmet clinical need for risk stratification strategies to improve variant interpretation and patient care. Here, we performed an unsupervised cluster analysis leveraging p53 mutagenesis datasets (Kato et al., 2003 & Giacomelli et al., 2018) that revealed five TP53 mutational clusters with unique mutation patterns, structural features, and functional consequences. Stratifying germline carriers based on the five clusters exposed important clinical characteristics to consider for patient management, such as ages-of-onset, tumor type development, and survival outcomes. In particular, we discovered an osteosarcoma-prone subgroup comprised of monomeric mutant p53 carriers with aggressive cancer phenotypes. We also identified a cluster of TP53 variants found more often in non-cancer and healthy older populations, and carriers of these variants that developed cancer had less “LFS-like” phenotypes including an older age-of-onset and a significantly higher frequency of colorectal cancers. Remarkably, our TP53 variant clustering strategy could also stratify breast cancer survival among germline carriers. This work provides a new framework to delineate the LFS spectrum toward the development of machine learning-based approaches for personalized cancer surveillance plans. Citation Format: Nicholas W. Fischer, Brianne Laverty, Ran Kafri, Kara N. Maxwell, Emma R. Woodward, Christian Kratz, David Malkin. TP53 mutational clusters stratify the Li-Fraumeni syndrome spectrum [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6198.

Optimizing antithrombotic therapy in patients with coexisting cardiovascular and gastrointestinal disease.

Balancing the safety and efficacy of antithrombotic agents in patients with gastrointestinal disorders is challenging because of the potential for interference with the absorption of antithrombotic drugs and for an increased risk of bleeding. In this Review, we address considerations for enteral antithrombotic therapy in patients with cardiovascular disease and gastrointestinal comorbidities. For those with gastrointestinal bleeding (GIB), we summarize a general scheme for risk stratification and clinical evidence on risk reduction approaches, such as limiting the use of concomitant medications that increase the risk of GIB and the potential utility of gastrointestinal protection strategies (such as proton pump inhibitors or histamine type 2 receptor antagonists). Furthermore, we summarize the best available evidence and potential gaps in our knowledge on tailoring antithrombotic therapy in patients with active or recent GIB and in those at high risk of GIB but without active or recent GIB. Finally, we review the recommendations provided by major medical societies, highlighting the crucial role of teamwork and multidisciplinary discussions to customize the antithrombotic regimen in patients with coexisting cardiovascular and gastrointestinal diseases.

Risk Prediction for Sudden Cardiac Death in the General Population: A Systematic Review and Meta-Analysis.

Objective: Identification of SCD risk is important in the general population from a public health perspective. The objective is to summarize and appraise the available prediction models for the risk of SCD among the general population. Methods: Data were obtained searching six electronic databases and reporting prediction models of SCD risk in the general population. Studies with duplicate cohorts and missing information were excluded from the meta-analysis. Results: Out of 8,407 studies identified, fifteen studies were included in the systematic review, while five studies were included in the meta-analysis. The Cox proportional hazards model was used in thirteen studies (96.67%). Study locations were limited to Europe and the United States. Our pooled meta-analyses included four predictors: diabetes mellitus (ES = 2.69, 95%CI: 1.93, 3.76), QRS duration (ES = 1.16, 95%CI: 1.06, 1.26), spatial QRS-T angle (ES = 1.46, 95%CI: 1.27, 1.69) and factional shortening (ES = 1.37, 95%CI: 1.15, 1.64). Conclusion: Risk prediction model may be useful as an adjunct for risk stratification strategies for SCD in the general population. Further studies among people except for white participants and more accessible factors are necessary to explore.

Influence of Impaired Diffusing Capacity and Sleep-disordered Breathing on Nocturnal Hypoxemia and Health Outcomes in Men with and without HIV.

Nocturnal hypoxemia is common in sleep-disordered breathing (SDB) and is associated with increased morbidity and mortality. Although impaired diffusing capacity of the lungs for carbon monoxide (DLCO) is associated with daytime hypoxemia, its influence on SDB-related nocturnal hypoxemia is not known. To characterize the effects of DLCO impairment on SDB-related nocturnal hypoxemia and associated health outcomes. Data from a multi-center cohort of men with and without HIV, with concomitant measures of DLCO and home-based polysomnography (N=544), were analyzed. Multivariable quantile regression models characterized associations between DLCO and several measures of SDB-related hypoxemia (e.g., total sleep time with oxygen saturation [SpO2]<90% [T90]). Structural equation models assessed associations between impaired DLCO and SDB-related hypoxemia measures with prevalent hypertension and type 2 diabetes. DLCO impairment (<80% predicted) was associated with sleep-related hypoxemia. Participants with severe SDB (apnea-hypopnea index≥30 events/hr) and impaired DLCO had a higher T90 (median difference: 15.0%; [95% CI: 10.3,19.7]) and average SDB-related desaturation (median difference: 1.0; [0.5, 1.5]), and lower nadir SpO2 (median difference: -8.2%; [-11.4, -4.9]) and average SpO2 during sleep (median difference: -1.1%; [-2.1, -0.01]), than those with severe SDB and preserved DLCO. A higher T90 was associated with higher adjusted odds of prevalent hypertension (OR 1.39; [1.14,1.70]) and type 2 diabetes (OR 1.25; [1.07,1.46]). DLCO impairment in severe SDB was associated with sleep-related hypoxemia, prevalent hypertension and type 2 diabetes. Assessment of SDB should be considered in those with impaired DLCO to guide testing and risk-stratification strategies.

Novel role of cardiovascular MRI to contextualise tuberculous pericardial inflammation and oedema as predictors of constrictive pericarditis.

Tuberculosis (TB) and human immunodeficiency virus/acquired immunodeficiency syndrome have reached epidemic proportions, particularly affecting vulnerable populations in low- and middle-income countries of sub-Saharan Africa. TB pericarditis is the commonest cardiac manifestation of TB and is the leading cause of constrictive pericarditis, a reversible (by surgical pericardiectomy) cause of diastolic heart failure in endemic areas. Unpacking the complex mechanisms underpinning constrictive haemodynamics in TB pericarditis has proven challenging, leaving various basic and clinical research questions unanswered. Subsequently, risk stratification strategies for constrictive outcomes have remained unsatisfactory. Unique pericardial tissue characteristics, as identified on cardiovascular magnetic resonance imaging, enable us to stage and quantify pericardial inflammation and may assist in identifying patients at higher risk of tissue remodelling and pericardial constriction, as well as predict the degree of disease reversibility, tailor medical therapy, and determine the ideal timing for surgical pericardiectomy.

Long QT Syndrome and the Risk of Sudden Death in Adult Patients: An In-depth Analysis of Clinical Correlates and Prognostic Factors

Long QT Syndrome (LQTS) is a hereditary or acquired cardiac disorder characterized by delayed ventricular repolarization, predisposing affected individuals to life-threatening arrhythmias. While extensively studied in the pediatric population, there is a paucity of comprehensive research focusing on the clinical implications and prognostic markers of LQTS in adults. This article aims to elucidate the association between Long QT Syndrome and the heightened risk of sudden death in adult patients, exploring pertinent clinical correlates and potential prognostic factors. A systematic literature review was conducted to identify relevant studies published between 2000 and 2024, utilizing databases such as PubMed, MEDLINE, and Cochrane Library. Eligible articles were critically appraised for methodological quality and relevance to adult populations with Long QT Syndrome. Data extraction encompassed demographics, genetic predispositions, clinical presentations, electrocardiographic findings, and outcomes, focusing on the incidence of sudden death. Preliminary findings underscore the significance of a prolonged QT interval as a critical marker for adverse cardiovascular events in adults with Long QT Syndrome. Additionally, the study examines the impact of genotype-phenotype correlations, gender-related differences, and the influence of comorbidities on the risk of sudden death. Furthermore, potential therapeutic interventions and risk stratification strategies will be discussed in light of recent advancements in the field. This review aims to bridge the existing knowledge gap regarding Long QT Syndrome in the adult population, emphasizing the need for heightened clinical awareness, risk stratification, and targeted interventions to mitigate the risk of sudden death in affected individuals. The synthesis of current evidence will contribute to a more nuanced understanding of the complex interplay between Long QT Syndrome and adverse outcomes in adults, facilitating the development of tailored therapeutic approaches and improved patient outcomes

Acute myocarditis: an overview of pathogenesis, diagnosis and management.

Acute myocarditis encompasses a diverse presentation of inflammatory cardiomyopathies with infectious and non-infectious triggers. The clinical presentation is heterogeneous, from subtle symptoms like mild chest pain to life-threatening fulminant heart failure requiring urgent advanced hemodynamic support. This review provides a comprehensive overview of the current state of knowledge regarding the pathogenesis, diagnostic approach, management strategies, and directions for future research in acute myocarditis. The pathogenesis of myocarditis involves interplay between the inciting factors and the subsequent host immune response. Infectious causes, especially cardiotropic viruses, are the most frequently identified precipitants. However, autoimmune processes independent of microbial triggers, as well as toxic myocardial injury from drugs, chemicals or metabolic derangements also contribute to the development of myocarditis through diverse mechanisms. Furthermore, medications like immune checkpoint inhibitor therapies are increasingly recognized as causes of myocarditis. Elucidating the nuances of viral, autoimmune, hypersensitivity, and toxic subtypes of myocarditis is key to guiding appropriate therapy. The heterogeneous clinical presentation coupled with non-specific symptoms creates diagnostic challenges. A multifaceted approach is required, incorporating clinical evaluation, electrocardiography, biomarkers, imaging studies, and endomyocardial biopsy. Cardiovascular magnetic resonance imaging has become pivotal for non-invasive assessment of myocardial inflammation and fibrosis. However, biopsy remains the gold standard for histological classification and definitively establishing the underlying etiology. Management relies on supportive care, while disease-specific therapies are limited. Although some patients recover well with conservative measures, severe or fulminant myocarditis necessitates aggressive interventions such as mechanical circulatory support devices and transplantation. While immunosuppression is beneficial in certain histological subtypes, clear evidence supporting antiviral or immunomodulatory therapies for the majority of acute viral myocarditis cases remains insufficient. Substantial knowledge gaps persist regarding validated diagnostic biomarkers, optimal imaging surveillance strategies, evidence-based medical therapies, and risk stratification schema. A deeper understanding of the immunopathological mechanisms, rigorous clinical trials of targeted therapies, and longitudinal outcome studies are imperative to advance management and improve the prognosis across the myocarditis spectrum.

Cardiac imaging correlates and predictors of stroke in patients with atrial fibrillation: a meta-analysis.

New nonclinical parameters are needed to improve the current stroke risk stratification schemes for patients with atrial fibrillation. This study aimed to summarize data on potential cardiac imaging correlates and predictors of stroke or systemic embolism in patients with atrial fibrillation. MEDLINE, EMBASE, and Web of Science were searched to identify all published studies providing relevant data through 16 November 2022. Random effects meta-analysis method was used to pool estimates. We included 64 studies reporting data from a pooled population of 56 639 patients. Left atrial spontaneous echo-contrast [adjusted odds ratio (aOR) 3.32, 95% confidence interval (CI) 1.98-5.49], nonchicken wing left atrial appendage (LAA) morphology (aOR 2.15, 95% CI 1.11-4.18), left atrial enlargement (aOR 2.12, 95% CI 1.45-3.08), and higher LAA orifice diameter (aOR 1.56, 95% CI 1.18-2.05) were highly associated with stroke. Other parameters associated with stroke included higher left atrial sphericity (aOR 1.14, 95% CI 1.01-1.29), higher left atrial volume (aOR 1.03, 95% CI 1.01-1.04), higher left atrial volume index (aOR 1.014, 95% CI 1.004-1.023), lower left atrial reservoir strain [adjusted hazard ratio (aHR) 0.86, 95% CI 0.76-0.98], higher left ventricular mass index (aOR 1.010, 95% CI 1.005-1.015) and E / e' ratio (aOR 1.12, 95% CI 1.07-1.16). There was no association between LAA volume (aOR 1.37, 95% CI 0.85-2.21) and stroke. These cardiac imaging parameters identified as potential predictors of thromboembolism may improve the accuracy of stroke risk stratification schemes in patients with atrial fibrillation. Further studies should evaluate the performance of holistic risk scores including clinical factors, biomarkers, and cardiac imaging.