Diabetes mellitus is a chronic disease that affects multiple organs and exhibits significant complications. The major outcomes of prolonged hyperglycemia are nephropathy, retinopathy, neuropathy, and cardiovascular events due to the glycation of lipids and proteins. To ensure a healthy lifestyle for diabetic patients, a treatment that delays the complications and simultaneously protects multiple organs is required. Sodium-glucose cotransporter inhibitors (SGLTi) inhibit the reabsorption of glucose from the kidney and shows promising benefits in renal and heart diseases. The major SGLT receptors are SGLT1 and SGLT2. Various trials are conducted to conclude their efficacy and show nephroprotective and cardioprotective roles independent of diabetic status. The FDA-approved SGLT2 inhibitors are empagliflozin (Jardiance®), canagliflozin (Invokana®), and dapagliflozin (Farxiga®), which are primarily used in type 2 diabetes mellitus (T2DM). They show a reduced rate of hospitalization for heart failure, cardiovascular disease mortality, all-cause mortality, and progression of diabetic kidney disease. It also shows improvement in the glycemic index; therefore, it is protective against the complications of diabetes irrespective of insulin release, thus avoids hypoglycemia. This review summarizes the data from the clinical trials that support the efficacy of SGLT2 inhibitors in reducing the risks of cardiovascular and renal outcomes in patients with T2DM.

Background: Amyloidosis is increasingly recognized as a contributor to heart failure, particularly among older adults and patients with heart failure with preserved ejection fraction (HFpEF). Despite advances in diagnostic imaging and disease-modifying therapies, amyloidosis remains underdiagnosed in many settings, and population-level data examining its co-occurrence with cardiovascular disease on death certificates are limited. This study examined two decades of national mortality data to evaluate deaths co-coded with amyloidosis and cardiovascular disease (CVD) in the United States and to assess temporal trends and demographic disparities in age-adjusted 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 years and older in the United States. The overall AAMR for deaths co-coded with amyloidosis and CVD increased from 4.40 in 1999 to 9.31 in 2020, with an AAPC of 3.49 ( p < 0.001). The most pronounced increase occurred between 2018 and 2020 (APC: 13.60). Rates were higher among men than women, with both sexes showing a marked increase in the last decade. African American or Black individuals had the highest rates (11.40), followed by White (5.11) and Hispanic (3.86) individuals. Rates were highest in the Northeast region (6.71). Metropolitan areas had higher rates than non-metropolitan areas (5.73 vs. 4.76), with a more pronounced increase in metropolitan regions. Conclusions: Age-adjusted mortality rates for deaths co-coded with amyloidosis and cardiovascular disease have increased over time, likely reflecting improved recognition and documentation. Higher rates of co-coded deaths were noted among men, African Americans, and individuals in the Northeast region, highlighting potential disparities in diagnostic access and recognition.

Background: Heart failure patients are frequently prescribed SGLT2 inhibitors, but the incremental real-world benefit of adding GLP-1 receptor agonists is uncertain. Methods: A retrospective propensity-matched cohort study was conducted using the TriNetX Global Collaborative Network (171 healthcare organizations). Adults aged ≥18 years with incident heart failure who initiated either dual SGLT2 inhibitor and GLP-1 receptor agonist therapy or SGLT2 inhibitor monotherapy within 1 month of the first heart failure diagnosis were compared. Outcomes over 365 days included all-cause mortality, all-cause hospitalization, acute myocardial infarction, atrial fibrillation/flutter, acute kidney failure, pulmonary edema, new-onset diuretic use, urinary tract infection, retinopathy, and laboratory hypoglycemia (glucose ≤ 70 mg/dL). Cox proportional hazards models were used; the proportional hazards assumption was formally tested. Bonferroni and Benjamini–Hochberg adjustments were applied for multiple comparisons. E-values quantified robustness to unmeasured confounding. Appendicitis was used as a negative control outcome. Results: After 1:1 propensity score matching, 3421 patients were included in each cohort. Cohorts were well-balanced (all standardized mean differences < 0.10). Over 365 days of follow-up, no significant differences were observed between dual therapy and monotherapy in all-cause mortality (HR 0.92, 95% CI 0.77–1.09), all-cause hospitalization (HR 1.16, 95% CI 0.96–1.40), acute myocardial infarction (HR 1.20, 95% CI 0.92–1.55), atrial fibrillation/flutter (HR 1.05, 95% CI 0.85–1.30), acute kidney failure (HR 1.05, 95% CI 0.89–1.26), new-onset diuretic use (HR 0.92, 95% CI 0.78–1.09), or urinary tract infection (HR 1.16, 95% CI 0.90–1.48). Dual therapy was associated with a significant increase in retinopathy (HR 2.66, 95% CI 1.81–3.93; Bonferroni p = 0.001; E-value 4.77, lower CI bound 3.01), and a modest increase in laboratory hypoglycemia (HR 1.22, 95% CI 1.04–1.44) and pulmonary edema (HR 1.35, 95% CI 1.06–1.70), both of which survived FDR but not Bonferroni adjustment. Prespecified subgroup analyses showed lower mortality with dual therapy in patients aged 18–64 (HR 0.64, 95% CI 0.43–0.93) and in women (HR 0.60, 95% CI 0.45–0.81). The negative control outcome (appendicitis) was non-significant. Conclusions: In a propensity-matched real-world cohort with a conservative cohort definition, dual SGLT2 inhibitor and GLP-1 receptor agonist therapy was not associated with significant differences in mortality or major cardiovascular outcomes compared with SGLT2 inhibitor monotherapy. Subgroup signals favoring dual therapy in younger and female patients, alongside safety signals for retinopathy and laboratory hypoglycemia, are hypothesis-generating and should be confirmed in prospective trials.

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.

Background: Finerenone and sodium–glucose cotransporter-2 inhibitors provide cardiovascular and renal benefits in patients with chronic kidney disease (CKD) and heart failure (HF), but real-world comparative evidence is limited. Methods: This retrospective study used the TriNetX database. Adults ≥ 40 years with CKD stages 1–5 and HF [LVEF > 40%; excluding end-stage renal disease (ESRD) or dialysis] receiving finerenone were compared with those on SGLT2 inhibitors. Propensity score matching (1:1) yielded 333 patients per cohort. Kaplan–Meier and Cox models estimated hazard ratios (HRs) with 95% confidence intervals. Results: After matching, baseline characteristics were reasonably balanced, with some residual imbalance remaining. All-cause mortality was similar between finerenone and SGLT2 inhibitors at 6 months (HR 0.98; 95% CI 0.50–1.90) and 1 year (HR 0.93; 95% CI 0.53–1.66). All-cause hospitalization or ER visits were also comparable at 6 months (HR 1.07; 95% CI 0.84–1.36) and 1 year (HR 1.04; 95% CI 0.83–1.29). Finerenone was associated with a modest, borderline reduction in HF hospitalization at 1 year, without consistent effects across timepoints or a mortality benefit; thus, this finding is hypothesis-generating (HR 0.81; 95% CI 0.66–0.99). Safety outcomes were similar between groups. Conclusions: In this real-world analysis, finerenone was associated with similar all-cause mortality, overall hospitalization, and renal safety outcomes compared with SGLT2 inhibitors, with a modest reduction in HF hospitalization at 1 year that should be interpreted cautiously given the exploratory nature of the study. These findings are hypothesis-generating and underscore the need for prospective head-to-head trials to better define optimal therapy sequencing in patients with HFpEF and CKD.

Background Valvular heart disease (VHD) and atrial fibrillation (AF) frequently coexist, presenting complex clinical challenges despite advances in diagnostics and therapeutics. Together, they contribute substantially to cardiovascular mortality. However, epidemiological patterns vary across demographics and regions Methods Mortality data from 1999–2023 were obtained from the CDC WONDER database. Deaths attributed to VHD (ICD-10: I30-I52) with co-diagnosed AF (ICD-10: I48) among adults ≥ 45 were included. Age-adjusted mortality rates (AAMRs) per 1,000,000 population were calculated. Autoregressive integrated moving average (ARIMA) models were used to project mortality trends through 2035. Results From 1999 to 2023, there were 172,511 VHD and Afib-related deaths in adults ≥ 45. AAMRs increased until 2021, followed by a slight decline to 8.86. The overall AAPC for VHD with AF was 4.01%. AAMR increase was consistent across all age groups, highest seen in 65 + individuals. Males had consistently higher AAMRs than females. AAPC for males was 4.44% and for females 3.52%. Non- Hispanic White had the highest AAMR (10.56 in 2021), followed by Hispanics (4.19). Regionally, the West had the highest AAMR (11.27), followed by Mid-West (9.94). Non-metropolitan areas had higher AAMR 8.96 compared to metropolitan areas (AAMR: 7.59). Most VHD related deaths were reported in inpatient settings (n = 396,451) and 12% involved co-diagnosed AF. Conclusion Mortality associated with VHD and AF in the U.S population aged ≥ 45 has shown a concerning increase. Predictive models indicate this trend may persist, highlighting the need for early detection, equitable healthcare access and public health interventions tailored to high-risk populations.