Weekly Cardiology Research Analysis
This week’s cardiology literature was dominated by high-impact advances in combination cardiorenal therapy, AI-enabled risk targeting, and novel acute heart-failure pharmacotherapy. A NEJM randomized trial showed upfront finerenone plus empagliflozin produces substantially greater albuminuria reduction than either agent alone in CKD with type 2 diabetes. A transformer-based survival model (TRisk) improved 10-year CVD risk discrimination and reduced high-risk labeling versus conventional tools. A
Summary
This week’s cardiology literature was dominated by high-impact advances in combination cardiorenal therapy, AI-enabled risk targeting, and novel acute heart-failure pharmacotherapy. A NEJM randomized trial showed upfront finerenone plus empagliflozin produces substantially greater albuminuria reduction than either agent alone in CKD with type 2 diabetes. A transformer-based survival model (TRisk) improved 10-year CVD risk discrimination and reduced high-risk labeling versus conventional tools. A randomized hemodynamic study found intravenous istaroxime safely improved blood pressure, cardiac output, and wedge pressure in pre‑cardiogenic shock. Together these signal shifts in therapy sequencing, precision prevention, and hemodynamic management.
Selected Articles
1. Finerenone with Empagliflozin in Chronic Kidney Disease and Type 2 Diabetes.
CONFIDENCE, a randomized trial, found that initial combination therapy with finerenone plus empagliflozin produced a 29–32% greater reduction in urinary albumin-to-creatinine ratio at 180 days compared with either agent alone among patients with CKD and type 2 diabetes, without new safety signals. Symptomatic hypotension, AKI, and hyperkalemia leading to discontinuation were uncommon.
Impact: Provides high-quality randomized evidence supporting simultaneous initiation of mineralocorticoid receptor antagonism and SGLT2 inhibition to achieve superior antiproteinuric effects, which may alter sequencing of cardiorenal therapies.
Clinical Implications: Consider earlier combination finerenone plus an SGLT2 inhibitor in patients with CKD and T2D to maximize antiproteinuric effect, while monitoring for hyperkalemia and renal function; long-term hard-outcome data are still needed.
Key Findings
- Combination therapy reduced UACR at day 180 by 29% vs finerenone alone (LS mean ratio 0.71; 95% CI 0.61–0.82).
- Combination therapy reduced UACR at day 180 by 32% vs empagliflozin alone (LS mean ratio 0.68; 95% CI 0.59–0.79).
- No unexpected safety signals; symptomatic hypotension, AKI, and hyperkalemia-related discontinuation were uncommon.
2. Refined selection of individuals for preventive cardiovascular disease treatment with a transformer-based risk model.
TRisk, a transformer-based survival model developed and validated on ~3 million linked EHRs, achieved superior discrimination (C-index 0.910) and higher net benefit versus QRISK3, while reducing the number of individuals labeled high risk by ~20.6% at a 10% threshold and ~34.6% at 15%. In diabetes cohorts, TRisk also outperformed a treat‑all approach by deselecting 24.3% at 10% with minimal false negatives.
Impact: Demonstrates that modern deep-learning survival models can materially improve targeting of preventive therapies, reducing overtreatment while maintaining event prevention—an actionable advance for population-level prevention strategies.
Clinical Implications: Health systems should prospectively evaluate implementation of TRisk to refine statin/antihypertensive initiation thresholds and to avoid unnecessary treatment in lower-benefit individuals; prospective impact trials are recommended.
Key Findings
- C-index in primary prevention population 0.910 (95% CI 0.906–0.913) with good calibration.
- Decision-curve analysis showed higher net benefit than QRISK3 across thresholds.
- At 10% and 15% thresholds TRisk reduced high-risk classifications by 20.6% and 34.6%, respectively; in diabetes TRisk deselected 24.3% at 10% with only 0.2% false negatives.
3. Safety and efficacy intravenous istaroxime up to 60 hours for patients with pre-cardiogenic shock.
In a randomized, double‑blind placebo‑controlled trial (n=90) of pre-cardiogenic shock due to acute heart failure, intravenous istaroxime (up to 1.0 µg/kg/min for ≤60 h) increased systolic blood pressure, raised cardiac output by ~0.66 L/min, and lowered pulmonary capillary wedge pressure by ~3.8 mmHg versus placebo, with effects persisting to 60 hours in prolonged infusions and no signal for malignant arrhythmias on Holter.
Impact: Randomized, double-blind evidence for a novel inotrope/lusitrope that improves hemodynamics without arrhythmic penalty in early shock—addresses an unmet need for agents that raise BP and CO while lowering filling pressures.
Clinical Implications: Istaroxime could be considered in monitored pre‑cardiogenic shock/acute heart failure settings to stabilize hemodynamics and potentially reduce vasopressor exposure; larger outcome trials are required before routine adoption.
Key Findings
- 6-hour SBP AUC significantly higher with istaroxime (LS mean difference 25.6 mmHg*hour; p=0.007).
- Cardiac output increased by ~0.66 L/min (p=0.017) and PCWP decreased by ~3.8 mmHg (p=0.0017) vs placebo.
- Durable effects to 60 hours in those infused ≥48 hours; Holter monitoring showed no increase in malignant arrhythmias.