This focused systematic review examines the role of the gut microbiota in cardiovascular disease (CVD). The review explores mechanisms linking gut dysbiosis with CVD via microbial metabolites such as trimethylamine-N-oxide (TMAO) and short-chain fatty acids (SCFAs), which affect inflammation, endothelial function, and lipid metabolism. Interventions including dietary modifications, probiotics, prebiotics, fecal microbiota transplantation, and pharmacological agents such as statins, rifaximin, and empagliflozin are evaluated for their impact on microbial composition and cardiovascular outcomes. Probiotic strains and fiber-rich diets demonstrated modest improvements in blood pressure, lipid profiles, and inflammatory markers. Studies revealed that gut microbiome alterations influence drug metabolism and bleeding risk in patients taking oral anticoagulants. Limited evidence suggests that modulation of the microbiota may reduce chemotherapy-induced cardiotoxicity. However, only nine eligible studies met the inclusion criteria, reflecting the early and heterogeneous nature of this research area. Consequently, these findings should be interpreted as exploratory and hypothesis-generating. The focused review emphasizes the need for large-scale trials to validate microbiome-targeted strategies in CVD prevention and management. This focused systematic review is registered with PROSPERO (ID: CRD420251022190).

Background: Atrial fibrillation (AF) and congestive heart failure (CHF) remain major contributors to cardiovascular mortality in the United States. When accompanied by underlying ischemic heart disease (IHD), mortality risk is amplified. Although IHD mortality declined in the early 2000s, recent data suggest a resurgence. Methods: This population-based study used the CDC Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database from 1999 to 2023. Deaths were identified using ICD-10 codes I48 (AF) and I50.0 (CHF) as multiple causes of death and I20–I25 (IHD) as the underlying cause. Adults aged ≥ 65 years were included. Crude mortality rates (CMRs) and age-adjusted mortality rates (AAMRs) were calculated. Temporal trends were analyzed using Joinpoint regression to estimate annual percent change (APC) and average annual percent change (AAPC). Future mortality trends were projected using autoregressive integrated moving average (ARIMA) model. Results: From 1999 to 2023, AF, CHF, and IHD accounted for 219,188 deaths among adults ≥ 65 years. The overall AAMR increased from 193.8 per million in 1999 to 220.1 per million in 2023, with a decline from 1999 to 2010 followed by a sustained rise. Males (108,732 deaths) showed the steepest increase (AAPC + 1.40%, p < 0.001), whereas females (110,456 deaths) experienced a modest decline (AAPC − 0.55%, p < 0.001). Non-Hispanic Black adults had the largest racial increase (AAPC + 1.21%, p < 0.001). Non-metropolitan areas showed the greatest geographic rise (AAPC + 1.67%, p < 0.001). Conclusion: Mortality involving AF and CHF with underlying IHD among U.S. adults ≥ 65 years declined only temporarily before reversing after 2010. Persistent racial and geographic disparities underscore gaps in prevention and acute cardiovascular care. Clinical Trial Registration: Not applicable.

Background: The diagnostic performance of fractional flow reserve (FFR) in the setting of acute coronary syndrome (ACS) remains unclear. We sought to perform an updated systematic review and meta‐analysis investigating the performance of FFR‐guided revascularization in the setting of ACS. Methods: Two main primary comparisons tested the major adverse cardiac events (MACE) rate at 1‐year of patients treated with an FFR‐guided strategy in ACS versus chronic coronary syndrome and an FFR‐guided versus angiographic‐guided strategy in acute coronary syndrome. Treatment effect was defined as the risk difference and was estimated with Bayesian random effect model with a conservative prior of no treatment effect. Kaplan–Meier estimates and their standard deviations were retrieved to maximum accuracy from cumulative incidence function/ survival function plots for studies with censoring. Results: We found 11 eligible trials (with a total of 13 029 patients) in this systematic review. Within the FFR‐guided strategy, acute coronary syndrome was associated with an increased risk of MACE at 1 year compared with chronic coronary syndrome (risk difference (RD): 1.9%, 95% credible interval [0.2% to 3.6%]). In contrast, among patients with ACS no difference in 1‐year MACE rate was observed between angiography‐guided versus FFR‐guided complete revascularization strategy (RD=0.9%, 95% CI [−1.3 to 3.2]). Conclusions: FFR‐guided strategy of lesions in acute coronary syndrome was associated with worse 1‐year MACE compared with FFR‐guided revascularization in chronic coronary syndrome reflecting the high‐risk nature of acute coronary syndrome patients. No difference in long‐term outcomes was seen from a FFR‐guided versus angiography‐guided approach in acute coronary syndrome. Further studies are needed to better understand and optimize the use of physiology in the ACS setting.

Background: Coronary artery disease (CAD) and heart failure with preserved ejection fraction (HFpEF) are major causes of morbidity and mortality. Systemic inflammation contributes to both, suggesting potential benefit from colchicine, though data in CAD-HFpEF are limited. Methods: We conducted a real-world study using the TriNetX Research Network, identifying 480,434 adults with CAD and HFpEF. Patients were categorized as colchicine users (n = 30,254) or non-users (n = 450,180). One-to-one propensity score matching yielded 28,941 patients per group. The primary outcome was a composite of acute myocardial infarction, stroke, all-cause mortality, and acute heart failure. Secondary outcomes included individual components, hospitalizations, atrial fibrillation, and gastrointestinal events, assessed at 1- and 3-year follow-up. Results: At 1 year, the primary outcome occurred in 16.9% of the colchicine group versus 19.8% of non-users (HR: 0.86, 95% CI: 0.81–0.91; p < 0.001). All-cause mortality was 11.4% versus 14.5% (HR: 0.77, 95% CI: 0.73–0.80; p < 0.001). At 3 years, the primary outcome occurred in 34.2% versus 39.7% (HR: 0.88, 95% CI: 0.85–0.92; p < 0.001), with acute heart failure slightly higher in the colchicine group (27.5% vs. 26.5%; HR: 1.04, 95% CI: 1.01–1.08; p = 0.009). Stroke was modestly reduced (HR: 0.93, 95% CI: 0.88–0.99; p = 0.014). No significant differences were seen in all-cause hospitalization, atrial fibrillation, or gastrointestinal events. Conclusions: In patients with CAD and HFpEF, colchicine was associated with lower short- and medium-term risk of composite cardiovascular events and mortality, with modest attenuation over time, suggesting early time-dependent association rather than sustained structural effects. Prospective randomized trials are warranted.

Background: Cardiogenic shock (CS) and chronic ischemic heart disease (CIHD) remain major contributors to cardiovascular mortality in the United States. Although mortality related to ischemic disease declined in the early 2000s, recent trends suggest a resurgence. Methods: This population-based study utilized the Centers for Disease Control and Prevention’s Wide-Ranging OnLine Data for Epidemiologic Research (CDC WONDER) database from 1999 to 2023. Deaths were identified using ICD-10 codes R57.0 (CS) and I25 (CIHD). Adults aged ≥ 45 years were included. Crude mortality rates (CMRs) and age-adjusted mortality rates (AAMRs) were calculated, with temporal changes assessed using Joinpoint regression to estimate Annual Percent Change (APC) and Average Annual Percent Change (AAPC). Results: Between 1999 and 2023, deaths attributed to CS and CIHD accounted for 78,903 cases among adults ≥ 45 years. Overall AAMR ranged from 35.88 per million in 1999 to 37.44 per million in 2023, with a downward trend from 1999 to 2012 followed by an upward trend thereafter. Males (51,080 deaths) exhibited rising mortality (AAPC: +0.50, p < 0.001), while females (27,823 deaths) showed a decline (AAPC: − 0.91, p < 0.0004). Non-Hispanic Black adults demonstrated the steepest increase (AAPC: +1.85, p < 0.001). The burden was greatest in adults ≥ 65 years, but the 45–64 group showed the fastest rise (AAPC: +1.67, p < 0.001). Conclusion: Mortality from cardiogenic shock and chronic ischemic heart disease among U.S. adults ≥ 45 years declined initially but reversed after 2012. Rising mortality in middle-aged adults, persistent racial disparities, and geographic inequities highlight urgent gaps in prevention and acute care.

Introduction : Cardiac amyloidosis (CA), most commonly caused by transthyretin (ATTR) or light chain (AL) deposition, is increasingly recognized as a contributor to heart failure, particularly in older adults and patients with heart failure with preserved ejection fraction (HFpEF). Despite advances in diagnostic imaging and disease-modifying therapies, CA remains underdiagnosed, and population-level data on its combined mortality burden with cardiovascular disease (CVD) are limited. Aims : This study aimed to analyze two decades of consecutive mortality data to investigate amyloidosis and cardiovascular disease (CVD) across the United States (US), identifying patterns and disparities in mortality rates. Methods : A retrospective analysis was conducted using mortality data from the CDC WONDER database spanning 1999–2020. Age-adjusted mortality rates (AAMRs) per 1,000,000 persons were calculated, and trends were assessed using Average Annual Percentage Change (AAPC) and Annual Percent Change (APC) using Joinpoint 5.0.2. Results : Between 1999 and 2020, 26,391 Amyloidosis and CVD-related deaths occurred among adults aged 25 and older in the US. The overall AAMR for Amyloidosis and CVD-related mortality increased from 4.40 in 1999 to 9.31 in 2020, with an AAPC of 3.49 (p < 0.001). Most striking was the recent steep rise in AAMRs from 2018 to 2020 with an APC of 13.60. Men exhibited higher AAMRs compared to women. Similar to the overall trend, AAMRs for both men and women had a steep incline in the last decade. African Americans or Blacks had the highest AAMRs (11.4) followed by White (5.11) and Hispanics (3.86). The highest mortality was in the Northeast region (AAMR: 6.71). Nonmetropolitan areas had higher AAMRs than metropolitan areas (5.73 vs 4.76), however, with a more remarkable increase in metropolitan areas. Conclusions :The prevalence of amyloidosis and cardiovascular disease-related deaths has risen markedly, especially between 2018 and 2020. Increased mortality rates were noted among men, African Americans, and individuals in the Northeast region. These patterns emphasize the necessity for focused public health initiatives.