Ibrahim, Ramzi

ABSTRACT Background Sodium‐glucose cotransporter 2 inhibitors (SGLT2‐Is) are primarily used to manage type 2 diabetes mellitus (T2DM) and heart failure (HF), but their impact on reducing stroke risk in patients with atrial fibrillation (AF) remains underexplored. We aimed to investigate the impact of SGLT2‐Is for stroke risk mitigation in patients with AF. Methods Using the TriNetX database, we performed a retrospective cohort study on patients ≥ 18 years with AF and on anticoagulation. These patients were then classified into two cohorts based on their use of SGLT2‐Is. To balance the baseline demographics, comorbidities, and medication use, propensity score matching (PSM) was used. The primary outcome was ischemic and hemorrhagic strokes, and the secondary outcomes were all‐cause mortality, all‐cause hospitalizations, need for AF cardioversion or antiarrhythmic drug initiation, and cardiac arrest. Adjusted odds ratio (aORs) and hazard ratios (HRs) were estimated for both the primary and secondary outcomes. Results A total of 152,778 patients with 76,389 patients were included in each cohort (SGLT2‐Is users, and non‐users) after PSM. The mean age of both SGLT2‐Is users and non‐users was 72.8 years. For the SGLT2‐Is users, the mean follow‐up period was 317 days, whereas the mean follow‐up period for the non‐users was 306 days. For the primary outcome, we found that SGLT2‐Is users had a lower risk of ischemic stroke (aOR: 0.889; 95% CI: 0.857–0.923) and hemorrhagic stroke (aOR: 0.682; 95% CI: 0.620–0.749) compared to non‐users. Regarding the secondary outcomes, SGLT2‐Is users also had lower risk for all‐cause mortality (aOR: 0.615; 95% CI: 0.595–0.636), all‐cause hospitalizations (aOR: 0.599; 95% CI: 0.587–0.611), need of AF cardioversion (aOR: 0.846; 95% CI: 0.813–0.881), antiarrhythmic drug initiation (aOR: 0.790; 95% CI: 0.766–0.815), and cardiac arrest (aOR: 0.643; 95% CI: 0.601–0.688). Conclusions SGLT2‐I use in patients with AF is associated with lower risks of stroke and other cardiovascular and non‐cardiovascular outcomes. Future prospective research is needed to validate these findings.

Abstract Aims Sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) improve heart failure (HF) outcomes but their effects on acute myocardial infarction (AMI) remain poorly characterized. This study aimed to evaluate the 1-year cardiovascular outcomes of SGLT2-Is among patients with AMI. Methods and results We conducted an observational, retrospective cohort study using TriNetX data, including patients aged ≥18 with AMI identified via ICD-10 codes regardless of left ventricular ejection fraction (LVEF), categorized by SGLT2-Is use. Propensity score matching (PSM) was performed to balance baseline demographics, comorbidities, and medication use. Adjusted odds ratios (aORs) were estimated for the primary outcome (recurrent AMI) and the secondary outcomes (acute HF hospitalizations, stroke, all-cause hospitalizations, all-cause mortality, new-onset atrial fibrillation, and cardiac arrest). After PSM, 89 554 patients were analysed (44 777 SGLT2-Is users; 44 777 non-users). The mean age was ∼68 years in both cohorts with a similarly high burden of cardiovascular comorbidities. Mean follow-up duration was 290.854 days for SGLT2-Is users and 284.465 days for non-users. SGLT2-Is use was linked to lower rates of recurrent AMI [aOR: 0.459; 95% confidence interval (CI): 0.367–0.551], all-cause hospitalizations (aOR: 0.782; 95% CI: 0.762–0.803), all-cause mortality (aOR: 0.640; 95% CI: 0.612–0.670), and cardiac arrest (aOR: 0.834; 95% CI: 0.773–0.900). No differences were observed in acute HF hospitalizations, new-onset atrial fibrillation, or stroke. Conclusion SGLT2-Is are associated with improved cardiovascular outcomes in patients with AMI, including reductions in recurrent AMI, all-cause hospitalizations and mortality, and cardiac arrest. These findings emphasize the need for prospective clinical trials involving patients with AMI and other cardiovascular comorbidities, regardless of LVEF, to confirm these results.

Cardiovascular diseases and cancer are the leading causes of morbidity and mortality in modern society. Expanding cancer therapies that have improved prognosis may also be associated with cardiotoxicity, and extended life span after survivorship is associated with the increasing prevalence of cardiovascular disease. As such, the field of cardio-oncology has been rapidly expanding, with an aim to identify cardiotoxicity and cardiac disease early in a patient who is receiving treatment for cancer or is in survivorship. Artificial intelligence is revolutionizing modern medicine with its ability to identify cardiac disease early. This article comprehensively reviews applications of artificial intelligence specifically applied to electrocardiograms, echocardiography, cardiac magnetic resonance imaging, and nuclear imaging to predict cardiac toxicity in the setting of cancer therapies, with a view to reduce early complications and cardiac side effects from cancer therapies such as chemotherapy, radiation therapy, or immunotherapy.

Lipoprotein(a) [Lp(a)] is a well-established causal risk factor for cardiovascular diseases (CVDs), as reported by multiple Mendelian randomization studies and large epidemiological studies. When elevated Lp(a) is combined with other risk factors, most notably elevated low-density lipoprotein cholesterol (LDL-C), a synergistic atherogenic effect has been reported. However, the current literature is conflicting regarding how Lp(a) interacts in the context of controlled LDL-C levels (e.g., <70 mg/dL) and whether reducing LDL-C can modify the atherogenic effect of Lp(a). In some studies, elevated Lp(a) was still significantly associated with a higher risk of cardiovascular events, despite controlled levels of LDL-C. In contrast, multiple studies have reported attenuation of the cardiovascular risk mediated by elevated Lp(a) with lower LDL-C levels. Moreover, the relationship between Lp(a) and triglycerides, high-density lipoprotein, and very low-density lipoprotein remains unclear. In this literature review, we summarize and discuss the current evidence regarding the interactions between Lp(a) and other lipid molecules, how they contribute to the pathogenesis of CVD, and future perspectives, particularly in the current era where promising targeted Lp(a)-lowering therapies are under development.

Abstract Introduction Gastrointestinal bleeding (GIB) is often encountered among patients with atrial fibrillation (AF) due to the use of anticoagulation. This study assesses disparities in GIB‐related mortality among decedents with AF in the United States. Methods GIB mortality data in patients with AF from 1999 to 2020 was queried from the CDC database. Decedent demographic information (age, sex, race and ethnicity, and geographic residence) was obtained from death certificates. We calculated age‐adjusted mortality rates (AAMRs) through the direct method and estimated the annual percentage change (APC) in mortality using log‐linear regression models. Results From 11,209 GIB‐related deaths among AF decedents, we observed an increase in AAMR from 0.12 in 1999 to 0.21 in 2020, particularly during the 2009 to 2020 period (APC +4.8, p < .001). Disproportionate mortality rates were noted in males (AAMR 0.18) and White populations (AAMR 0.15) as compared to females (AAMR 0.13) and Black populations (AAMR 0.10), respectively. Rural regions also reported higher mortality (AAMR 0.18) than urban areas (AAMR 0.14). Mortality shifts in urban regions remained stagnant from 1999 to 2009 (APC –0.15, p = .806) followed by an increase from 2009 to 2020 (APC +4.83, p < .001). However, mortality increased consistently from 1999 to 2020 in rural regions (APC +4.08, p < .001). The Northeast US exhibited the highest mortality rate (AAMR 0.18), followed by the Midwest (AAMR 0.16), West (AAMR 0.14), and South (AAMR 0.13). Conclusions Disparities in GIB mortality among AF decedents were identified. These findings accentuate the need for targeted interventions to mitigate GIB risks in vulnerable subgroups.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, impacting approximately 6.1 million adults in the United States, with projections to increase two-fold by 2030. AF significantly increases the risk of stroke and other adverse cardiovascular events, leading to increased morbidity and mortality. The 2023 ACC/AHA/ACCP/HRS guidelines present a paradigm shift in AF management, moving from a duration-based classification to a more comprehensive, patient-centered approach. This includes a novel AF classification system that emphasizes early detection and intervention, including risk factors and lifestyle modification tailored to each patient’s risk profile. Moreover, the recommendations advocate for a multidisciplinary care model, ensuring coordinated management involving primary care providers and specialists. Primary care providers play a crucial role in initiating risk factor management and lifestyle interventions, even before the development of AF. This review aims to thoroughly examine the guidelines for the diagnosis and management of AF and equip general internists with the necessary insights to navigate the evolving landscape of AF care effectively.

Background Hyperlipidemia is a major cardiovascular disease (CVD) risk factor, but there are limited data on its mortality trends in CVD over time. We assessed annual hyperlipidemia‐related CVD mortality trends in the United States, including the COVID‐19 pandemic's impact. Methods and Results Mortality data were obtained from the Centers for Disease Control and Prevention repository between 1999 and 2020 among patients ≥15 years old, using International Classification of Diseases, Tenth Revision ( ICD‐10 ) codes for hyperlipidemia (E78.0–E78.5) and CVD (I00–I99). Age‐adjusted mortality rates (AAMRs) per 1 000 000 population were standardized to the 2000 US population. Log‐linear regression models were used to evaluate mortality shifts. Average annual percentage change from 1999 to 2019 was used to project 2020 AAMRs, estimating pandemic‐attributed excess deaths. From 1999 to 2020, 483 155 hyperlipidemia‐related CVD deaths occurred. Despite a general CVD mortality decline, hyperlipidemia‐related CVD AAMRs rose from 36.33 in 1999 to 99.77 in 2019. Ischemic heart diseases (AAMR 49.39) were the leading cause, whereas hypertension had the highest mortality increase (average annual percentage change +10.23%). Mortality rates were higher in men (AAMR 104.87) and non‐Hispanic (AAMR 82.49), and rural populations (AAMR 89.98). Highest mortality was observed in Black populations (AAMR 84.35), those ≥75 years old (AAMR 646.45), and Western US regions (AAMR 96.88). During the first pandemic year, deaths exceeded projections by 10.55%, with notable increases among ages 35 to 75 (14.23%), Hispanic (17.96%), Black (14.82%), and urban (11.68%) groups. Conclusions Hyperlipidemia‐related CVD mortality has risen over the past 2 decades, further heightened by the COVID‐19 pandemic, with higher impact on men, Black Americans, the older population, and rural residents. Further study is needed to understand contributing factors and mitigate disparities.

Background Peripartum cardiomyopathy (PPCM) outcomes have been previously linked to demographic and social factors. The social vulnerability index (SVI) is a measure of social vulnerability in the United States. We explored PPCM disparities and the impact of SVI on PPCM mortality. Methods and Results Mortality from 1999 to 2020, SVI, and demographic data were obtained from CDC databases. County‐specific SVI rankings were linked to PPCM age‐adjusted mortality rates (AAMRs), allowing for a comparative analysis of AAMRs across both cumulative populations and subpopulations to identify disparities. All US counties were then stratified into low‐ and high‐SVI groups, facilitating comparison of SVI rankings by estimation of excess‐deaths per 1 000 000 person‐years attributable to greater social vulnerability and rate ratios (RR) through univariable Poisson regression. We identified a total of 1026 deaths related to PPCM between 1999 and 2020. Overall AAMR increased from 0.180 in 1999 to 0.326 in 2020. Black populations (AAMR: 1.081) and Southern US counties (AAMR: 0.444) had the highest AAMRs compared with other racial and US census groups, respectively. Higher SVI accounted for 0.172 excess deaths per 1 000 000 person‐years (RR=1.800). Among Black and White populations, higher SVI also accounted for 0.248 and 0.071 excess deaths per 1 000 000 person‐years, respectively. Similar impacts of greater social vulnerability were observed when comparing the US census regions (Northeast RR=1.609, Midwest RR=1.819, South RR=1.934, West RR=1.776). Conclusions PPCM mortality disparities exist across racial and geographic populations in the United States. A greater burden of social vulnerability is associated with higher PPCM mortality on a national level.

Heart failure with preserved ejection fraction (HFpEF) includes almost half of heart failure cases typified by a specific clinical syndrome. Despite diagnostic and management advances, HFpEF still presents a diagnostic challenge and a paucity of therapies specifically aimed at enhancing survival and improving quality of life is still lacking. This review elucidates the diagnostic complexity of HFpEF, highlighting the use of both subjective and objective criteria within algorithmic frameworks. It also examines the significant impact of comorbidities on the progression of HFpEF. Additionally, we explore the latest evidence on targeting these comorbidities therapeutically, although the benefits to mortality are still limited.