Daily Cardiology Research Analysis
Three advances span therapy optimization, biomarker-guided diagnostics, and secondary prevention. Individual-patient data from RALES and EMPHASIS-HF show mineralocorticoid receptor antagonists benefit HFrEF across body weights with greater effect at higher weight. In ischemic stroke, admission NT-proBNP ≥505 pg/mL strongly predicts in-hospital atrial fibrillation detection but performs poorly for post-discharge AF. After AMI, participation in exercise-based cardiac rehabilitation and higher phys
Summary
Three advances span therapy optimization, biomarker-guided diagnostics, and secondary prevention. Individual-patient data from RALES and EMPHASIS-HF show mineralocorticoid receptor antagonists benefit HFrEF across body weights with greater effect at higher weight. In ischemic stroke, admission NT-proBNP ≥505 pg/mL strongly predicts in-hospital atrial fibrillation detection but performs poorly for post-discharge AF. After AMI, participation in exercise-based cardiac rehabilitation and higher physical activity lowered subsequent stroke risk.
Research Themes
- Phenotype-tailored pharmacotherapy in heart failure
- Biomarker-guided detection of atrial fibrillation after stroke
- Rehabilitation and lifestyle to prevent post-MI cerebrovascular events
Selected Articles
1. Mineralocorticoid receptor antagonists in heart failure with reduced ejection fraction according to body weight.
An individual patient data analysis of RALES and EMPHASIS-HF (n=4,386 with weight data) shows MRAs reduce HF hospitalization/cardiovascular death and all-cause mortality across weight strata, with larger benefits at higher body weight. Effects were consistent by sex and across trials.
Impact: This IPD analysis refines patient selection by showing amplified MRA benefit in heavier HFrEF patients, informing precision use without denying therapy to lighter patients.
Clinical Implications: Do not withhold MRAs in obese HFrEF; if anything, prioritize adherence and monitoring given amplified benefit. Weight alone should not deter MRA initiation; monitor hyperkalemia similarly across weights.
Key Findings
- Across 4,386 patients, MRAs reduced the composite of HF hospitalization or cardiovascular death versus placebo irrespective of weight.
- The magnitude of benefit on the primary composite and HF hospitalization increased with higher body weight, both as categorical and continuous variables.
- Trends toward greater reductions in cardiovascular and all-cause mortality with higher body weight; consistent across sexes and within each trial.
Methodological Strengths
- Individual patient data from two randomized, placebo-controlled trials (RALES, EMPHASIS-HF)
- Consistent effects across prespecified subgroups and across separate trial analyses
Limitations
- Post hoc analysis; body weight was not randomized and may proxy for unmeasured adiposity or comorbidities
- No mechanistic biomarkers to explain differential benefit by weight
Future Directions: Prospective, stratified studies by adiposity measures (e.g., visceral fat) and aldosterone signaling; evaluate safety (hyperkalemia) and optimal dosing across weight phenotypes.
AIMS: Obesity is associated with excessive adipocyte-derived aldosterone secretion, independent of the classical renin-angiotensin-aldosterone cascade, and mineralocorticoid receptor antagonists (MRAs) may be more effective in obese patients with heart failure (HF) with reduced ejection fraction (HFrEF). METHODS AND RESULTS: Using individual patient-level data from two randomized placebo-controlled trials, RALES and EMPHASIS-HF, the effect of MRA treatment, compared with placebo, and outcomes were assessed according to body weight at baseline, examined both as a categorized (above/below median) and continuous variable. The primary outcome was the composite of HF hospitalization or cardiovascular death. Of the 4400 patients randomized in RALES and EMPHASIS-HF, 4386 (99.7%) participants had data on body weight at baseline. The median body weight was 75 kg (25th-75th percentile, 65-85 kg). Compared with placebo, MRA treatment reduced the risk of the primary composite outcome, each of its components, and all-cause death across body weight categories. However, the beneficial effect of MRA treatment on the primary composite outcome and HF hospitalization was larger with higher body weight, whether weight was examined as a categorized or as a continuous variable. In addition, there was a trend towards a greater benefit with MRA treatment on cardiovascular death and all-cause death with higher body weight. Similar associations were found in both men and women, and when the trials were analysed individually. CONCLUSION: In patients with HFrEF, the beneficial effect of MRA treatment on clinical outcomes appeared to be larger in individuals with higher body weight. TRIAL REGISTRATION: NCT00232180.
2. Role of NT-proBNP for Atrial Fibrillation Detection After Ischemic Stroke: A Time-Dependent Relationship.
Across two prospective cohorts (n=2,292), admission NT-proBNP strongly predicted in-hospital AFDAS (AUROC 0.83); a 505 pg/mL cutoff had 82% sensitivity, 71% specificity, and 96% NPV. Predictive performance for AF detected after discharge was modest (AUROC 0.65), with 20% having normal NT-proBNP at baseline.
Impact: Defines a pragmatic NT-proBNP threshold to triage rhythm monitoring intensity after ischemic stroke, distinguishing in-hospital versus post-discharge detection windows.
Clinical Implications: Use NT-proBNP ≥505 pg/mL to prioritize intensive telemetry/prolonged inpatient monitoring for AF detection; do not rely on NT-proBNP to exclude post-discharge AF—outpatient prolonged monitoring remains necessary for many.
Key Findings
- AFDAS occurred in 16% (374/2,292) within 1 year; 72% were detected during hospitalization and 28% after discharge.
- Admission NT-proBNP predicted in-hospital AFDAS with AUROC 0.83; a 505 pg/mL cutoff yielded 82% sensitivity, 71% specificity, and 96% negative predictive value.
- Predictive performance for post-discharge AFDAS was modest (AUROC 0.65), and 20% had normal NT-proBNP (<125 pg/mL) at admission.
Methodological Strengths
- Pooled analysis of two prospective cohorts with standardized early biomarker measurement (≤24 hours)
- Clear outcome definition (≥30 s AF/flutter) and external validation of cutoff
Limitations
- Observational cohorts; potential heterogeneity between studies and unmeasured confounding
- Did not evaluate serial biomarker trajectories or cost-effectiveness of biomarker-guided monitoring
Future Directions: Randomized strategies allocating monitoring based on NT-proBNP, integration with ECG analytics and other biomarkers, and evaluation of outcomes/costs.
BACKGROUND: Atrial fibrillation detected after stroke (AFDAS) affects secondary stroke prevention, yet identification can be challenging. Easily accessible cardiac blood biomarkers such as NT-proBNP (N-terminal pro-B-type natriuretic peptide) could guide diagnostic workup, but optimal cutoff values and the time-dependent relationship between NT-proBNP and AFDAS are unclear. We aimed (1) to externally validate earlier presented NT-proBNP cutoffs for atrial fibrillation prediction and (2) to assess the time-dependent relationship of NT-proBNP and early in-hospital AFDAS versus AFDAS after discharge. METHODS: We conducted a pooled data analysis of patients with ischemic stroke from the prospective international multicenter BIOSIGNAL (Biomarker Signature of Stroke Aetiology) cohort study (European Stroke Centers from October 2014 to October 2017) and the prospective single-center Graz stroke pathway study (Austria from May 2018 to August 2020). AFDAS was defined as ≥30-s atrial fibrillation/flutter diagnosed within 1 year post-admission and categorized in in-hospital versus after discharge. NT-proBNP was assessed ≤24 hours of symptom onset. The association between NT-proBNP and AFDAS was evaluated by a multivariable logistic regression analysis. RESULTS: AFDAS was diagnosed in 374 (16%) of 2292 patients with ischemic stroke (median age, 74 years; 42% female), 268 (72%) during hospitalization, and 106 (28%) after discharge (median duration of hospitalization, 15 days). NT-proBNP levels at admission had a good predictive capacity for in-hospital AFDAS (area under the receiver operating characteristic curve, 0.83 [95% CI, 0.81-0.86]). For patients diagnosed with AFDAS after discharge, the predictive capacity of NT-proBNP was poor (area under the receiver operating characteristic curve, 0.65 [95% CI, 0.60-0.70]), and 20% had normal NT-proBNP values <125 pg/mL at admission. The NT-proBNP cutoff of 505 pg/mL exhibited high sensitivity (82%) and specificity (71%) for in-hospital AFDAS, with a negative predictive value of 96%. CONCLUSIONS: In patients with ischemic stroke, the admission NT-proBNP cutoff of 505 pg/mL seems to be a reliable predictor for in-hospital AFDAS, while the predictive capacity of NT-proBNP for AFDAS after discharge is limited. Our results might influence the designs of future secondary stroke prevention trials.
3. Cardiac rehabilitation and physical activity decrease the risk of stroke after acute myocardial infarction: A nationwide cohort study in Sweden.
In a nationwide cohort of 86,637 post-AMI patients, participation in exercise-based cardiac rehab (24 sessions) was associated with lower total stroke risk (aHR 0.85). Self-reported ≥150 min/week of physical activity also reduced risk (aHR 0.79), and six-day-per-week activity was linked to lower intracerebral hemorrhage versus the general population.
Impact: Provides robust, population-scale evidence that EBCR participation and higher physical activity after AMI are associated with stroke risk reduction, supporting stronger implementation of rehab programs.
Clinical Implications: Refer eligible AMI survivors to EBCR and counsel for at least 150 minutes/week of moderate activity; benefits extend to stroke prevention, not just cardiac outcomes.
Key Findings
- EBCR participation after AMI was associated with reduced total stroke risk versus non-participation (aHR 0.85; 95% CI 0.80–0.91).
- Self-reported ≥150 min/week physical activity reduced total stroke risk (aHR 0.79; 95% CI 0.75–0.83).
- Six-day-per-week activity post-AMI conferred no excess total/ischemic stroke risk versus general population and lower intracerebral hemorrhage risk (aHR 0.59; 95% CI 0.35–0.98).
Methodological Strengths
- Nationwide, double-cohort design with matched general population comparators
- Large sample size and time-to-event analyses with adjusted hazard ratios
Limitations
- Observational design with potential residual confounding and selection bias into EBCR
- Physical activity was self-reported, introducing measurement error
Future Directions: Evaluate strategies to increase EBCR uptake and sustained physical activity; assess causal effects via pragmatic trials and study dose–response relationships.
BACKGROUND: Stroke and acute myocardial infarction (AMI) rank among the leading causes of mortality. Physical activity and exercise are recommended as part of rehabilitation after AMI to prevent cardiovascular events, but the importance for stroke prevention has not been investigated using population-based data. OBJECTIVES: To determine associations between participation in exercise-based cardiac rehabilitation (EBCR) and self-reported physical activity with the risk of total stroke, ischemic stroke, and intracerebral hemorrhage after AMI. METHODS: This was a nationwide, double cohort study conducted across all coronary care units in Sweden between 2005 and 2020, combined with registered data from the general population. Participation in EBCR (24 physiotherapist-led sessions over 4 months) and self-reported physical activity were assessed at a median of 55 days (range 28-90) after hospital discharge. Stroke incidence was followed until death or censoring on December 31, 2021. RESULTS: A total of 86,637 people with AMI (mean age 64.0, SD 9.0 years; 26 % female), and 259,911 (1:3) age, sex, and region of birth matched individuals from the general population were included. Participation in EBCR after AMI was associated with a lower risk of total stroke (adjusted hazard ratio, aHR 0.85; 95 % confidence interval, CI 0.80-0.91) compared to non-participants, as was ≥150 min of physical activity per week (aHR 0.79, 95 % CI 0.75-0.83). Those reporting physical activity 6 days per week after AMI did not have an increased risk of total stroke or ischemic stroke compared to the general population (aHR 1.03, 95 % CI 0.87-1.23; and aHR 1.17, 95 % CI 0.97-1.41), and were at lower risk of intracerebral hemorrhage (aHR 0.59, 95 % CI 0.35-0.98). CONCLUSIONS: EBCR and higher levels of physical activity are associated with a decreased risk of stroke after AMI. Cardiac rehabilitation programs and regular and physical activity should be promoted after AMI to decrease the burden of stroke. Swedish Ethical Review Authority Registration number: 2021-03645.