Daily Cardiology Research Analysis
Three impactful cardiology studies emerged today: a multinational NEJM RCT shows acute normovolemic hemodilution does not reduce transfusions in cardiac surgery; an individual participant-level pooled analysis supports finerenone for HFmrEF/HFpEF, lowering cardiovascular death or HF hospitalization; and a hierarchical Bayesian meta-analysis in Heart finds cerebral embolic protection devices during TAVI do not meaningfully reduce stroke.
Summary
Three impactful cardiology studies emerged today: a multinational NEJM RCT shows acute normovolemic hemodilution does not reduce transfusions in cardiac surgery; an individual participant-level pooled analysis supports finerenone for HFmrEF/HFpEF, lowering cardiovascular death or HF hospitalization; and a hierarchical Bayesian meta-analysis in Heart finds cerebral embolic protection devices during TAVI do not meaningfully reduce stroke.
Research Themes
- Transfusion strategies and blood conservation in cardiac surgery
- Cardiorenal-metabolic modulation for HFmrEF/HFpEF
- Periprocedural stroke prevention during TAVI
Selected Articles
1. A Randomized Trial of Acute Normovolemic Hemodilution in Cardiac Surgery.
In a 32-center randomized trial (n=2010), acute normovolemic hemodilution did not reduce the proportion of patients receiving allogeneic red-cell transfusion during hospitalization after cardiac surgery (27.3% vs 29.2%; RR 0.93, P=0.34). Mortality and safety outcomes were similar between groups.
Impact: This high-quality multicenter RCT provides definitive evidence that ANH does not meaningfully reduce transfusion exposure in modern cardiac surgery, informing perioperative blood management policies.
Clinical Implications: Routine ANH to reduce transfusion in cardiac surgery is not supported; programs should prioritize proven strategies (restrictive thresholds, antifibrinolytics, cell salvage) and tailor ANH to specific indications rather than broad use.
Key Findings
- ANH did not lower allogeneic red-cell transfusion incidence vs usual care (27.3% vs 29.2%; RR 0.93; P=0.34).
- 30-day or in-hospital mortality was similar (1.4% vs 1.6%).
- Surgery for postoperative bleeding was numerically higher with ANH (3.8% vs 2.6%).
Methodological Strengths
- Multinational, multicenter randomized controlled design with adequate sample size (n=2010).
- Prespecified outcomes and clinically relevant primary endpoint; trial registered.
Limitations
- Single-blind design; potential performance bias.
- No detailed transfusion protocol harmonization across centers; practice variability may dilute effects.
Future Directions: Identify subgroups or procedural contexts where ANH may confer benefit (e.g., complex redo surgery, high bleeding risk) and evaluate multimodal blood management bundles in pragmatic trials.
BACKGROUND: Patients undergoing cardiac surgery often receive red-cell transfusions, along with the associated risks and costs. Early intraoperative normovolemic hemodilution (i.e., acute normovolemic hemodilution [ANH]) is a blood-conservation technique that entails autologous blood collection before initiation of cardiopulmonary bypass and reinfusion of the collected blood after bypass weaning. More data are needed on whether ANH reduces the number of patients receiving allogeneic red-cell transfusion. METHODS: In a multinational, single-blind trial, we randomly assigned adults from 32 centers and 11 countries who were undergoing cardiac surgery with cardiopulmonary bypass to receive ANH (withdrawal of ≥650 ml of whole blood with crystalloids replacement if needed) or usual care. The primary outcome was the transfusion of at least one unit of allogeneic red cells during the hospital stay. Secondary outcomes were death from any cause within 30 days after surgery or during the hospitalization for surgery, bleeding complications, ischemic complications, and acute kidney injury. RESULTS: A total of 2010 patients underwent randomization; 1010 were assigned to ANH and 1000 to usual care. Among patients with available data, 274 of 1005 (27.3%) in the ANH group and 291 of 997 (29.2%) in the usual-care group received at least one allogeneic red-cell transfusion (relative risk, 0.93; 95% confidence interval, 0.81 to 1.07; P = 0.34). Surgery for postoperative bleeding was performed in 38 of 1004 patients (3.8%) in the ANH group and 26 of 995 patients (2.6%) in the usual-care group. Death within 30 days or during hospitalization occurred in 14 of 1008 patients (1.4%) in the ANH group and 16 of 997 patients (1.6%) in the usual-care group. Safety outcomes were similar in the two groups. CONCLUSIONS: Among adults undergoing cardiac surgery, ANH did not reduce the number of patients receiving allogeneic red-cell transfusion. (Funded by the Italian Ministry of Health; ANH ClinicalTrials.gov number, NCT03913481.).
2. Efficacy and Safety of Finerenone in Heart Failure With Preserved Ejection Fraction: A FINE-HEART Analysis.
Across 3 trials with participant-level data (n=7,008 HFmrEF/HFpEF; median follow-up 2.5 years), finerenone reduced cardiovascular death or heart failure hospitalization versus placebo (HR 0.87; 95% CI 0.78–0.96; P=0.008), with consistent effects across studies, supporting use in cardio-renal-metabolic risk settings.
Impact: This prespecified IPD pooled analysis extends finerenone benefits to HFmrEF/HFpEF, a population with limited disease-modifying therapies, integrating evidence across large outcome trials.
Clinical Implications: Consider finerenone for HFmrEF/HFpEF patients with cardio-renal-metabolic risk, alongside guideline-directed therapy, to reduce CV death/HF hospitalization. Monitor potassium and renal function due to MRA class effects.
Key Findings
- Finerenone reduced the composite of cardiovascular death or HF hospitalization (HR 0.87; P=0.008).
- Effects were consistent across FIDELIO-DKD, FIGARO-DKD, and FINEARTS-HF trials.
- Population included older adults (mean 71 years) with substantial female representation (44%).
Methodological Strengths
- Prespecified individual participant-level pooled analysis across three phase III outcome trials.
- Time-to-event modeling stratified by trial; large effective sample and follow-up.
Limitations
- Pooled analysis inherits trial selection criteria; not a new randomized comparison within HFpEF alone.
- Potential heterogeneity in background therapies and populations across contributing trials.
Future Directions: Dedicated RCTs in HFpEF/HFmrEF to confirm morbidity/mortality benefits, evaluate synergy with SGLT2 inhibitors/ARNI, and refine patient selection (e.g., CKD/T2D phenotypes).
BACKGROUND: Pooling data from participants with heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF) from all completed outcomes trials evaluating finerenone to date may enhance understanding of its safety and efficacy in this high-risk and heterogeneous population. OBJECTIVES: In this prespecified participant-level pooled analysis of the FIDELIO-DKD, FIGARO-DKD, and FINEARTS-HF trials (FINE-HEART), we evaluated the safety and efficacy of finerenone in individuals with HFmrEF/HFpEF. METHODS: The treatment effects of finerenone vs placebo on cardiovascular death or heart failure hospitalization were evaluated using Cox proportional hazards regression models stratified by trial. Additional endpoints included cardiovascular death, HF hospitalization, new-onset atrial fibrillation, and all-cause death. RESULTS: Among 18,991 pooled trial participants, 7,008 (36.9%) had HFmrEF/HFpEF (mean age, 71 ± 10 years; 44% female). Over a median follow-up of 2.5 years, finerenone reduced cardiovascular death or heart failure hospitalization compared with placebo (HR: 0.87 [95% CI: 0.78-0.96]; P = 0.008). Consistent effects were observed across trials (P CONCLUSIONS: This participant-level pooled analysis of 3 large-scale outcomes trials supports the use of finerenone in individuals with HFmrEF/HFpEF across a broad range of cardiovascular-kidney-metabolic risk. (FINE-HEART: An Integrated Pooled Analysis of Finerenone across 3 Phase III Trials of Heart Failure and Chronic Kidney Disease and Type 2 Diabetes; CRD42024570467).
3. When absence of evidence equates to evidence of absence: the case of routine use of cerebral embolic protection devices in transcatheter aortic valve implantation.
In a hierarchical Bayesian meta-analysis of eight RCTs (n=11,590), cerebral embolic protection during transfemoral TAVI did not achieve a clinically meaningful reduction in all stroke (ARD −0.17%; NNT 588; posterior probability of benefit <1%) or disabling stroke, arguing against routine CEP use.
Impact: Synthesizing all randomized evidence with Bayesian methods provides near-conclusive evidence that current CEP devices lack clinically relevant benefit, guiding resource allocation and device use policies.
Clinical Implications: Routine CEP use during TAVI should be reconsidered; focus on stroke risk mitigation via procedural optimization, antithrombotic strategies, and patient selection rather than device-based protection.
Key Findings
- Across 8 RCTs (n=11,590), all-stroke RR median 0.94 (95% CrI 0.72–1.25) with ARD −0.17% (NNT 588).
- Disabling stroke showed ARD −0.36% (NNT 278), with <1% posterior probability of clinically relevant benefit.
- Results robust to hierarchical Bayesian modeling and updated evidence base.
Methodological Strengths
- Hierarchical Bayesian meta-analysis with absolute risk translations (ARD/NNT) and clinically defined relevance threshold.
- Exclusive inclusion of RCTs; updated systematic search and registration (PROSPERO).
Limitations
- Device heterogeneity and learning-curve effects across trials.
- Event rates relatively low, limiting precision for rare disabling stroke subtypes.
Future Directions: Evaluate targeted use in very-high-risk anatomies or novel protection concepts; alternatively, shift research focus to procedural stroke mechanisms and pharmacologic prevention.
OBJECTIVES: This updated hierarchical Bayesian meta-analysis aims to integrate the latest randomised controlled trials (RCTs) on the use of cerebral embolic protection (CEP) in transcatheter aortic valve implantation (TAVI) into previously available data, providing a definite answer to the clinical effectiveness of CEP in TAVI patients. METHODS: A systematic search was updated on 31 March 2025. RCTs were included when comparing transfemoral TAVI with use of CEP versus transfemoral TAVI without CEP. The primary outcome was all stroke, while the secondary outcome was disabling stroke. A hierarchical Bayesian meta-analysis was performed on the (log) relative risk (RR) scale and transformed to absolute risk differences (ARDs) and numbers needed to treat (NNTs). The threshold for clinical relevance was based on published expert consensus and established on 1.1% ARD (NNT 91). RESULTS: The study was updated with one new RCT, totalling a number of eight RCTs (n=11 590, CEP n=5921 patients, control n=5669 patients). The prevalence of all stroke and disabling stroke was 2.9% and 1.4% in the control group. The median RR for all stroke was 0.94 (95% credible interval (CrI) 0.72-1.25), translating to a mean of -0.17% ARD (NNT 588), and a posterior probability of a clinically relevant CEP effect of <1%. The median RR for disabling stroke was 0.76 (95% CrI 0.44-1.23), translating to a mean of -0.36% ARD (NNT 278), and a posterior probability of a clinically relevant CEP effect of <1%. CONCLUSION: Current-generation CEP devices are ineffective in reducing periprocedural TAVI-stroke risk to a clinically relevant degree, rendering future trials with these devices futile. PROSPERO REGISTRATION NUMBER: CRD42023407006.