Daily Cardiology Research Analysis
A phase 2 randomized trial showed that sacubitril/valsartan regresses diffuse myocardial fibrosis in hypertensive heart disease beyond blood pressure lowering. A large JAMA policy analysis of U.S. veterans found that the MISSION Act reduced travel time but was associated with worse 30-day outcomes after PCI and CABG for geographically eligible patients. A contemporary JACC cohort demonstrated that patients with heart failure and improved ejection fraction still face substantial risks, underscori
Summary
A phase 2 randomized trial showed that sacubitril/valsartan regresses diffuse myocardial fibrosis in hypertensive heart disease beyond blood pressure lowering. A large JAMA policy analysis of U.S. veterans found that the MISSION Act reduced travel time but was associated with worse 30-day outcomes after PCI and CABG for geographically eligible patients. A contemporary JACC cohort demonstrated that patients with heart failure and improved ejection fraction still face substantial risks, underscoring the importance of maintaining guideline-directed therapy.
Research Themes
- Antifibrotic remodeling therapies in hypertensive heart disease
- Health policy impacts on cardiovascular procedural outcomes
- Management and risk in heart failure with improved ejection fraction
Selected Articles
1. Effects of sacubitril/valsartan on hypertensive heart disease: the REVERSE-LVH randomized phase 2 trial.
In a 52-week open-label randomized trial of 78 patients with hypertensive LVH, sacubitril/valsartan produced a greater reduction in CMR-measured interstitial volume than valsartan despite similar blood pressure control. LV mass, LA volume, estimated filling pressure, and NT-proBNP/hs-troponin T also improved, supporting antifibrotic benefits beyond hemodynamics.
Impact: This is the first randomized trial to demonstrate regression of diffuse myocardial fibrosis with sacubitril/valsartan independent of blood pressure lowering in hypertensive heart disease.
Clinical Implications: Supports preferential consideration of sacubitril/valsartan for hypertensive LVH patients at high risk of heart failure, and motivates phase 3 outcome trials to test whether antifibrotic remodeling translates into fewer clinical events.
Key Findings
- Sacubitril/valsartan reduced interstitial volume more than valsartan (−5.2 ± 5.4 vs −2.5 ± 3.1 mL; P=0.006) with similar 24-h SBP.
- Secondary endpoints favored sacubitril/valsartan: lower LV mass, smaller LA volume, lower estimated LV filling pressure, and improved NT-proBNP and hs-troponin T.
- No significant differences in other volumetric/functional/mechanical markers, indicating targeted antifibrotic effects.
Methodological Strengths
- Randomized allocation with active comparator and 52-week follow-up
- Quantitative CMR endpoint for diffuse interstitial fibrosis with blinded imaging analysis
Limitations
- Open-label design and modest sample size (n=78)
- Surrogate endpoints without clinical outcomes; single-country phase 2 study
Future Directions: Conduct multicenter phase 3 trials testing whether antifibrotic remodeling with sacubitril/valsartan reduces HF events and mortality; explore imaging-genomic markers to select responders.
Diffuse interstitial fibrosis is associated with adverse outcomes in hypertensive heart disease and may be reversible. Sacubitril/valsartan could offer greater anti-fibrotic effects than valsartan alone. In the REVERSE-LVH phase 2 open-labelled trial (clinicaltrials.gov NCT: 03553810; funded by the National Medical Research Council of Singapore), 78 patients with essential hypertension and left ventricular hypertrophy (LVH) were randomized 1:1 to sacubitril/valsartan or valsartan for 52 weeks. Primary endpoint was a change in interstitial volume, assessed using cardiovascular magnetic resonance. Despite similar 24-hour systolic blood pressure at 52 weeks (125 ± 11 vs. 126 ± 11 mmHg; P = 0.762), sacubitril/valsartan resulted in a greater absolute reduction in interstitial volume compared to valsartan (-5.2 ± 5.4 vs. -2.5 ± 3.1 mL; P = 0.006). Secondary endpoints showed significant differences favoring sacubitril/valsartan in LV mass, left atrial volume, estimated LV filling pressure, and improved cardiac circulating biomarkers (N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T). Other markers of cardiac volumes, function and mechanics were similar between the two treatment arms. Here we show the potential myocardial benefits of sacubitril/valsartan beyond blood pressure control, though larger studies are needed to confirm their clinical relevance.
2. Impact of the MISSION Act on Quality and Outcomes of Major Cardiovascular Procedures Among Veterans.
Using a difference-in-differences design, the MISSION Act substantially reduced travel times for veterans living far from VA centers but was associated with higher 30-day MACE after PCI (+2.8 percentage points) and CABG (+8.1 percentage points); AVR outcomes were unchanged.
Impact: Provides robust national evidence that access expansion may trade off with short-term outcomes for complex cardiovascular procedures, informing policy and network design.
Clinical Implications: Referral strategies should balance access with procedural quality; when shifting cases to non-VA sites, implement quality oversight and selective referral to high-performing centers.
Key Findings
- Travel times decreased markedly for far patients after MISSION (eg, PCI: −30.5 minutes difference-in-differences; P<.001).
- 30-day MACE increased for far vs near patients after MISSION for PCI (+2.8 percentage points; P<.001) and CABG (+8.1 percentage points; P<.001); AVR showed no significant difference.
- The cohort included 43,000 PCI, 23,301 CABG, and 14,682 AVR procedures across the contiguous U.S.
Methodological Strengths
- Large national cohort with difference-in-differences causal framework
- Procedure-specific analyses across PCI, CABG, and AVR with standardized outcomes
Limitations
- Observational design with potential residual confounding and selection bias
- Limited granularity on operator/center-level quality metrics and case complexity
Future Directions: Link center-level quality metrics and patient-level risk to guide network design; evaluate targeted contracting and feedback to improve non-VA outcomes.
IMPORTANCE: The Department of Veterans Affairs (VA) Maintaining Internal Systems and Strengthening Integrated Outside Networks (MISSION) Act expanded opportunities for veterans to obtain care outside the VA. However, the impact on health care outcomes is uncertain. OBJECTIVE: To measure the MISSION Act's impact on travel times and outcomes of percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), and aortic valve replacement (AVR). DESIGN, SETTING, AND PARTICIPANTS: This retrospective difference-in-differences cohort study included veterans receiving nonemergent/nonurgent PCI, CABG, or AVR between October 2016 and September 2022 in non-VA hospitals under MISSION Act coverage or in VA hospitals in the 48 contiguous US states or the District of Columbia. Analyses were conducted in 2023-2024. EXPOSURES: Veterans eligible for non-VA care under the MISSION Act by living far from ( >60 minutes) the nearest VA medical center vs veterans living near (≤60 minutes) a VA medical center. MAIN OUTCOMES AND MEASURES: Major adverse cardiovascular events (MACE), defined as rehospitalization for cardiovascular cause or mortality within 30 days of the procedure, and travel times for care were the primary outcomes.
3. Guideline-Directed Medical Therapy and Outcomes Among Patients With Heart Failure With Improved Ejection Fraction.
Among 28,292 incident HFrEF patients, 30.6% achieved HFimpEF within 12 months. Although event rates were lower than in persistent HFrEF, HFimpEF patients still had substantial risks (worsening HF: 17.4 vs 34.1 per 100 person-years; death: 5.7 vs 11.0 per 100 person-years), and reductions in GDMT after HFimpEF were observed and associated with modestly higher risk.
Impact: Defines the contemporary burden and residual risk of HFimpEF at scale and highlights a potential care gap—de-escalation of GDMT after EF improvement.
Clinical Implications: Continue and optimize GDMT even after EF normalizes; establish protocols and reminders to prevent unintended therapy withdrawal in HFimpEF.
Key Findings
- HFimpEF occurred in 8,656 of 28,292 incident HFrEF patients (30.6%) within 12 months.
- Event rates remained clinically meaningful: worsening HF 17.4 vs 34.1 per 100 person-years and death 5.7 vs 11.0 per 100 person-years for HFimpEF vs persistent HFrEF (HR ~0.52–0.58).
- GDMT use marginally decreased after HFimpEF; withdrawal was modestly associated with higher risk.
Methodological Strengths
- Large, integrated health system cohort with contemporary therapy and imaging data
- Clear operational definition of HFimpEF and comparison against persistent HFrEF
Limitations
- Observational design with potential misclassification of EF and unmeasured confounding
- Medication exposure assessed administratively; adherence and titration granularity limited
Future Directions: Interventional studies to test GDMT continuation vs de-escalation strategies in HFimpEF; deploy EHR-based nudges to sustain therapy.
BACKGROUND: The prevalence of heart failure with improved ejection fraction (HFimpEF) is anticipated to increase with the availability and implementation of novel pharmacotherapy for heart failure with reduced ejection fraction (HFrEF). However, there are limited data on contemporary epidemiology, management, and outcomes for this clinical entity. OBJECTIVES: The aim of this study was to describe epidemiology, guideline-directed medical therapy (GDMT), and outcomes among patients with HFimpEF across a large, diverse, multisite integrated health care delivery system. METHODS: Patients who were diagnosed with incident HFrEF between January 2013 and December 2022 across the Kaiser Permanente Northern California integrated health care delivery system were identified. Rates of incident HFimpEF, defined as HFrEF with a follow-up ejection fraction >40% and with >10% absolute left ventricular ejection fraction improvement within 12 months of incident HFrEF diagnosis, were identified. GDMT was examined at the time of incident HFrEF and HFimpEF and in the year following HFimpEF. Rates of worsening heart failure events and death were examined and compared among those with HFimpEF vs persistent HFrEF.