Daily Cardiology Research Analysis
Three impactful cardiology studies advance therapy, surgery, and risk prediction. A prespecified secondary analysis of the SCORED trial shows the dual SGLT1/2 inhibitor sotagliflozin reduces MI, stroke, and total MACE in T2D with CKD. A large cohort reveals sex-specific prosthesis–patient mismatch thresholds after surgical AVR, and a 49,224-person imaging cohort shows social vulnerability independently predicts MACE across CAC strata.
Summary
Three impactful cardiology studies advance therapy, surgery, and risk prediction. A prespecified secondary analysis of the SCORED trial shows the dual SGLT1/2 inhibitor sotagliflozin reduces MI, stroke, and total MACE in T2D with CKD. A large cohort reveals sex-specific prosthesis–patient mismatch thresholds after surgical AVR, and a 49,224-person imaging cohort shows social vulnerability independently predicts MACE across CAC strata.
Research Themes
- Cardiometabolic therapeutics and ischemic event reduction
- Sex-specific risk in valve surgery and prosthesis–patient mismatch
- Health equity and imaging-based risk stratification
Selected Articles
1. Effect of sotagliflozin on major adverse cardiovascular events: a prespecified secondary analysis of the SCORED randomised trial.
In patients with type 2 diabetes and chronic kidney disease, sotagliflozin reduced total MACE versus placebo (HR 0.77) and independently reduced myocardial infarction (HR 0.68) and stroke (HR 0.66). Benefits were consistent across subgroups, highlighting a potential ischemic risk reduction unique to dual SGLT1/2 inhibition.
Impact: This is the first robust evidence that a dual SGLT1/2 inhibitor reduces MI and stroke in T2D with CKD, extending beyond the heart failure benefits typical of SGLT2 inhibitors.
Clinical Implications: For T2D patients with CKD at high ischemic risk, sotagliflozin may be prioritized to reduce MI and stroke in addition to heart failure benefits; care teams should consider dual SGLT1/2 inhibition when selecting glucose-lowering therapy.
Key Findings
- Sotagliflozin reduced total MACE vs placebo (4.8 vs 6.3 events per 100 person-years; HR 0.77, 95% CI 0.65-0.91).
- Myocardial infarction was reduced (1.8 vs 2.7 events per 100 person-years; HR 0.68, 95% CI 0.52-0.89).
- Stroke was reduced (1.2 vs 1.8 events per 100 person-years; HR 0.66, 95% CI 0.48-0.91).
- Effects were consistent across stratified subgroups without evidence of heterogeneity.
Methodological Strengths
- Prespecified secondary analysis within a randomized, double-blind, placebo-controlled trial.
- Large sample size (n=10,584) with event adjudication and consistent subgroup effects.
Limitations
- Secondary analysis may be hypothesis-generating despite prespecification.
- Trial stopped early; follow-up duration for ischemic endpoints not fully detailed in the abstract.
Future Directions: Head-to-head comparisons with SGLT2-only inhibitors and mechanistic studies of SGLT1 inhibition on ischemic pathways are warranted; evaluate generalizability beyond T2D with CKD.
BACKGROUND: Sodium-glucose co-transporter (SGLT)-2 inhibitors have shown consistent benefit in improving heart failure-related outcomes but not ischaemic cardiovascular events such as myocardial infarction or stroke. We assessed if the dual SGLT1/2 inhibitor sotagliflozin improves ischaemic outcomes. METHODS: We did a prespecified secondary analysis of the SCORED trial, which was a double-blind, placebo-controlled, randomised clinical trial enrolling patients (aged ≥18 years) with type 2 diabetes, chronic kidney disease (estimated glomerular filtration rate [eGFR] 25-60 mL/min per 1·73 m
2. Sex-related differences in prosthesis-patient mismatch after surgical aortic valve replacement and long-term outcomes.
In 7,319 surgical AVR patients (median follow-up 12.6 years), PPM was more prevalent in women (31.9% vs 19.7%) and associated with higher all-cause (HR 1.30) and cardiovascular mortality (HR 1.39). After adjustment, VARC-3 PPM remained independently associated with outcomes only in women, while sex-specific spline-derived EOAi thresholds linked PPM with outcomes in both sexes.
Impact: Findings support sex-specific EOAi thresholds to define PPM and improve long-term risk stratification after AVR, potentially informing prosthesis sizing and guideline criteria.
Clinical Implications: Surgeons should consider sex-specific EOAi thresholds to minimize PPM risk, particularly in women. Preoperative planning and prosthesis selection may change to achieve better effective orifice matching and outcomes.
Key Findings
- PPM was more prevalent in women vs men (31.9% vs 19.7%, P<0.0001); severe PPM was rare but more frequent in women (2.4% vs 0.6%).
- PPM associated with all-cause mortality (HR 1.30, 95% CI 1.20-1.40) and cardiovascular mortality (HR 1.39, 95% CI 1.23-1.57).
- After multivariable adjustment, VARC-3 PPM remained independently associated with outcomes only in women.
- Spline-derived sex-specific EOAi thresholds linked PPM with outcomes in both sexes, suggesting higher thresholds may be needed in men.
Methodological Strengths
- Large single-region cohort (n=7,319) with prospective follow-up and national mortality adjudication.
- Use of standardized PPM definitions (VARC-3) and advanced modeling (spline-derived thresholds).
Limitations
- Observational design with potential residual confounding.
- Single regional health system; external generalizability needs validation.
Future Directions: External validation of sex-specific EOAi thresholds across diverse populations and integration into surgical planning tools; assess impact on reoperation, symptoms, and quality of life.
BACKGROUND AND AIMS: Prosthesis-patient mismatch (PPM) is associated with dismal prognosis after aortic valve replacement (AVR). Sex differences in PPM outcomes remain poorly explored. Therefore, this study aims to evaluate sex-specific impact in PPM after surgical AVR. METHODS: Between 2000 and 2021, 7319 patients underwent surgical AVR at the Institut Universitaire de Cardiologie et de Pneumologie de Québec. Prosthesis-patient mismatch was defined by using the indexed effective orifice area (EOAi) and by applying the Valve Academic Research Consortium-3 (VARC-3) criteria. The cohort was followed up prospectively from surgical AVR until November 2023. The primary endpoint was defined as long-term mortality and the secondary endpoint as long-term cardiovascular (CV) and perioperative mortality. Mortality was established and CV mortality was adjudicated by Quebec national database. RESULTS: Any-degree PPM resulted more prevalent in women than in men (31.9% vs. 19.7%, P < .0001) with rare incidence of severe PPM (2.4% vs. 0.6%, P < .0001) according to VARC-3 definition. Over a median follow-up of 12.6 years, there were 3231 (44.1%) all-cause deaths, with 1238 (16.9%) from CV causes. Prosthesis-patient mismatch was associated with all-cause mortality (hazard ratio 1.30, 95% CI 1.20-1.40; P < .0001) and CV mortality (hazard ratio 1.39, 95% CI 1.23-1.57; P < .0001) in the whole cohort without interaction between sexes (P ≥ .74). After comprehensive multivariable adjustment, VARC-3 PPM remained independently associated with outcome only in women (P ≤ .04). Adapting PPM definition according to spline-derived EOAi thresholds disaggregated by sex, PPM was independently associated with outcome in both sexes (P ≤ .04). CONCLUSIONS: Sex-specific EOAi thresholds associated with outcomes emerged in this large regional study. This finding suggests that PPM definition in men may follow higher EOAi thresholds than in women.
3. Interplay Between Social Vulnerability Index and Coronary Artery Calcium Scores With Major Adverse Cardiovascular Events.
In a no-cost, community CAC screening cohort (n=49,224), SVI independently predicted 8-year MACE, with risk increasing monotonically across SVI quartiles and an HR of 1.54 when comparing higher vs lower social vulnerability. SVI’s prognostic value persisted across all CAC categories, underscoring the need to integrate social determinants into imaging-based risk models.
Impact: Bridges imaging and social epidemiology, demonstrating that social vulnerability adds prognostic information beyond CAC. This has implications for targeted prevention and equitable care delivery.
Clinical Implications: Risk stratification and preventive strategies should account for SVI alongside CAC. Health systems may prioritize outreach and intensive risk management for high-SVI individuals even with low-to-moderate CAC.
Key Findings
- In 49,224 participants, higher SVI was associated with more comorbidities and higher CAC.
- 8-year MACE increased monotonically with SVI quartile; HR 1.54 (95% CI 1.24–1.90) for higher vs lower SVI.
- SVI independently predicted adverse outcomes across all CAC strata (0, 1–99, 100–399, ≥400).
Methodological Strengths
- Very large community-based cohort with 8-year follow-up and stratified CAC categories.
- Multivariable Cox modeling adjusting for demographics and metabolic factors.
Limitations
- Observational design with potential residual confounding and referral biases.
- SVI derived at census-tract level may not capture individual-level social risk.
Future Directions: Prospective integration of SVI into CAC-based risk calculators and trials testing targeted preventive interventions in high-SVI groups.
BACKGROUND: Coronary artery calcium (CAC) scoring predicts cardiovascular risk, but social determinants of health may play a role in its prognostic ability. We examined whether the Social Vulnerability Index (SVI) modifies the association between CAC and major adverse cardiovascular events (MACE) in a community-based screening cohort. METHODS: We studied 49 224 participants without known cardiovascular disease referred for CAC scanning from 2014 to 2022 based on cardiovascular risk factors. SVI was determined for each participant based on the census tract. We examined 8-year incidence of MACE (myocardial infarction, stroke, heart failure, revascularization, death) by SVI quartile across CAC score strata (0, 1-99, 100-399, ≥400). Cox proportional hazard models estimated hazard ratios for MACE, associated with demographics, metabolic factors, and CAC. RESULTS: Higher SVI was associated with female sex, non-White race, greater comorbidities, and higher CAC scores. The 8-year MACE rate increased monotonically by SVI quartile, with a hazard ratio of 1.54 (95% CI, 1.24-1.90,