Daily Cardiology Research Analysis
A first-in-class randomized trial (STORM-PE) shows mechanical thrombectomy plus anticoagulation rapidly reverses RV strain vs anticoagulation alone in intermediate-high risk pulmonary embolism with comparable short-term safety. Long-term analyses from FOURIER support targeting very low LDL-C (<40 mg/dL) after ischemic stroke without a rise in hemorrhagic stroke. MESA trajectory data indicate that rising albuminuria independently predicts future heart failure, atrial fibrillation, and coronary ev
Summary
A first-in-class randomized trial (STORM-PE) shows mechanical thrombectomy plus anticoagulation rapidly reverses RV strain vs anticoagulation alone in intermediate-high risk pulmonary embolism with comparable short-term safety. Long-term analyses from FOURIER support targeting very low LDL-C (<40 mg/dL) after ischemic stroke without a rise in hemorrhagic stroke. MESA trajectory data indicate that rising albuminuria independently predicts future heart failure, atrial fibrillation, and coronary events, underscoring kidney–heart cross talk.
Research Themes
- Interventional management of submassive pulmonary embolism
- Ultra-low LDL cholesterol targets in secondary stroke prevention
- Albuminuria trajectories as cardiovascular risk stratifiers
Selected Articles
1. Randomized Controlled Trial of Mechanical Thrombectomy With Anticoagulation Versus Anticoagulation Alone for Acute Intermediate-High Risk Pulmonary Embolism: Primary Outcomes from the STORM-PE Trial.
In this first RCT of mechanical thrombectomy for intermediate-high risk PE, computer-assisted vacuum thrombectomy plus anticoagulation achieved a significantly greater reduction in RV/LV ratio at 48 hours versus anticoagulation alone, with earlier normalization of vital signs and similar 7-day major adverse event rates. Findings support rapid reperfusion to unload the RV in carefully selected, normotensive PE patients.
Impact: This is the first randomized evidence that mechanical thrombectomy improves a key imaging marker of RV strain in submassive PE with acceptable short-term safety, informing ongoing debates about escalation beyond anticoagulation.
Clinical Implications: When expertise and systems are available, mechanical thrombectomy can be considered for intermediate-high risk PE with RV strain to rapidly reverse RV overload while maintaining acceptable short-term safety; definitive trials powered for hard clinical outcomes are still needed.
Key Findings
- CAVT plus anticoagulation produced a larger 48-hour reduction in RV/LV ratio than anticoagulation alone (mean difference 0.27; 95% CI 0.12–0.43).
- Earlier normalization of vital signs was observed with CAVT versus anticoagulation alone.
- Seven-day major adverse event rates (clinical deterioration requiring rescue therapy, PE-related death, symptomatic recurrent PE, major bleeding) were comparable between groups.
Methodological Strengths
- Randomized, multicenter design with blinded core-lab imaging assessment
- Independent clinical events adjudication and predefined endpoints
Limitations
- Modest sample size (N=100) limits precision and subgroup analyses
- Primary endpoint was an imaging surrogate (RV/LV ratio) with short 48-hour horizon; limited hard outcomes and short safety follow-up (7 days)
Future Directions: Larger blinded RCTs powered for mortality, hemodynamic collapse, and quality-of-life endpoints should compare thrombectomy against anticoagulation and other reperfusion options (e.g., CDT), and refine selection criteria and timing.
BACKGROUND: Patients with intermediate-high risk pulmonary embolism (PE) have an elevated right-to-left-ventricular (RV/LV) diameter ratio and are at risk of early clinical decompensation and mortality. Reperfusion therapy aims to rapidly relieve acute RV pressure overload and normalize hemodynamics. STORM-PE is the first reported randomized controlled trial (RCT) to test the efficacy and evaluate the safety of mechanical thrombectomy (MT), specifically computer assisted vacuum thrombectomy (CAVT) with anticoagulation (AC) compared to AC alone. METHODS: STORM-PE is an international RCT with 1:1 randomization to CAVT with AC or AC alone. Eligible adults had acute onset (symptoms ≤14 days), intermediate-high risk PE, and were normotensive, with an RV≤LV ratio ≥1.0 on computed tomography pulmonary angiography and elevated cardiac biomarkers. The primary endpoint analysis tested for a difference between groups for the change in RV/LV ratio at 48 hours, assessed by a blinded independent imaging core laboratory. Secondary endpoints included major adverse events (MAE) within 7 days (a composite of clinical deterioration necessitating rescue therapy, PE-related mortality, symptomatic recurrent PE, and major bleeding), adjudicated by an external clinical events committee. Additional outcomes included change in vital signs and core lab assessed PA obstruction at 48 hours. RESULTS: A total of 100 patients enrolled across 22 sites were randomized to CAVT (N=47) or AC alone (N=53). Baseline characteristics were comparable between arms. At 48 hours, mean reduction in RV/LV ratio was greater for CAVT (0.52±0.37) than AC (0.24±0.40), a difference of 0.27 (95% CI, 0.12, 0.43; CONCLUSIONS: CAVT was superior to AC alone in reducing RV/LV ratio within 48 hours in intermediate-high risk PE patients, accompanied by earlier normalization of vital signs and comparable MAE rates to AC.
2. Efficacy and Safety of Very Low Achieved LDL-Cholesterol in Patients with Prior Ischemic Stroke.
Across FOURIER and its open-label extension, patients with prior ischemic stroke who achieved very low LDL-C levels (including <40 mg/dL and even <20 mg/dL) had progressively lower risks of MACE and ischemic stroke without a clear increase in hemorrhagic stroke. These data support intensifying lipid lowering in secondary prevention after ischemic stroke.
Impact: Provides long-term, stroke-specific evidence that achieving ultra-low LDL-C confers benefit without an apparent hemorrhagic penalty, informing aggressive lipid targets in high-risk secondary prevention.
Clinical Implications: In ASCVD patients with prior ischemic stroke, clinicians should consider more intensive LDL-C lowering (e.g., PCSK9 inhibitors atop statins/ezetimibe) targeting <55 mg/dL and potentially <40 mg/dL when feasible, balancing cost and access.
Key Findings
- Among 5,291 prior-stroke patients, lower achieved LDL-C strata (including <40 mg/dL and <20 mg/dL) were associated with stepwise reductions in the primary composite endpoint.
- All stroke and ischemic stroke incidences decreased monotonically with lower achieved LDL-C.
- No clear increase in hemorrhagic stroke was observed at very low achieved LDL-C levels.
Methodological Strengths
- Large sample size with long-term follow-up across RCT and open-label extension
- Granular achieved LDL-C categorization with stroke-specific endpoints
Limitations
- Non-randomized comparison by achieved LDL-C introduces potential confounding (treatment adherence, baseline risk)
- Generalizability limited to trial-eligible ASCVD populations and PCSK9 inhibitor availability
Future Directions: Pragmatic trials or emulation studies testing LDL-C targets post-stroke, cost-effectiveness analyses of PCSK9 strategies, and safety surveillance for intracranial hemorrhage at ultra-low LDL levels.
BACKGROUND: Patients with prior ischemic stroke are at high risk for recurrent stroke and other major adverse cardiovascular events (MACE). The benefits of achieving very low levels of low-density lipoproteins-cholesterol (LDL-C) in such patients is unclear. METHODS: We analyzed patients with prior ischemic stroke enrolled in FOURIER, a randomized placebo-controlled trial studying evolocumab in patients with stable atherosclerotic cardiovascular disease (median follow-up 2.2 years), and through the open-label extension (FOURIER-OLE) period (additional median follow-up 5 years), to examine the relationship between achieved LDL-C and the long-term incidence of the primary endpoint (cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina or coronary revascularization) and stroke-related endpoints. RESULTS: The analysis included 5,291 patients with prior ischemic stroke (more than 4 weeks old). A total of 666 (12.6%), 1410 (26.6%), 586 (11.1%), 508 (9.6%) and 2121 (40.1%) patients achieved LDL-C values of <20, 20 to <40, 40 to <55, 55 to <70 and ≥70 mg/dL, respectively. The incidence of the primary endpoint, all stroke, and ischemic stroke each decreased in a monotonic fashion with lower achieved LDL-C levels on a continuous scale (P CONCLUSIONS: In patients with prior ischemic stroke, it appeared that the lower the LDL-C, down to levels below 40 mg/dL, the lower the risk of MACE, including recurrent stroke, without a clear increase in risk of hemorrhagic stroke. These findings support the concept that more intensive LDL-C lowering in patients with prior ischemic stroke may be warranted.
3. Longitudinal Trajectories of Albuminuria and Risk of Subclinical and Clinical Heart Failure, Atrial Fibrillation, and Coronary Heart Disease: the MESA Study.
Using latent trajectory modeling in MESA, persistently moderate-to-high or rapidly rising UACR identified individuals with substantially higher risks of HF (notably HFpEF), AF, and CHD, independent of baseline UACR and even among those initially normoalbuminuric. Trajectories correlated with higher NT-proBNP, hs-TnT, and myocardial fibrosis by T1 mapping.
Impact: Shifts risk assessment from single UACR measurements to longitudinal trajectories, providing actionable insight for earlier prevention in normoalbuminuric individuals who develop progressive albuminuria.
Clinical Implications: Incorporate serial UACR monitoring into cardiovascular prevention, especially in multi-ethnic populations, to identify rising-risk phenotypes and intensify BP, RAAS, SGLT2i, and lifestyle interventions before overt disease.
Key Findings
- Three UACR trajectory classes were identified; the “sustained medium-to-high” (5-year) and “rapid rise” (10-year) groups (~8% each) had 1.5–3.7× higher risks of HF, AF, CHD, and HF/death composites.
- Associations persisted after adjustment for baseline UACR and even among baseline normoalbuminuric individuals.
- High-risk trajectories correlated with elevated NT-proBNP, hs-TnT, and increased native T1/ECV indicating myocardial fibrosis.
Methodological Strengths
- Large, multi-ethnic prospective cohort with latent class mixed modeling over 5- and 10-year windows
- Integration of biomarkers (NT-proBNP, hs-TnT) and myocardial T1 mapping to link trajectories with pathophysiology
Limitations
- Observational design with potential residual confounding and measurement variability in UACR
- Trajectory-based classifications may be sensitive to visit timing and missingness patterns
Future Directions: Test whether targeting rising UACR trajectories with RAAS/SGLT2i/intensive BP control reduces HFpEF/AF/CHD; evaluate cost-effectiveness of serial UACR monitoring in primary prevention.
AIMS: We examined whether trajectories of urine albumin-creatinine ratio (UACR) over 5- and 10-year periods were associated with subclinical and clinical heart failure (HF), heart failure subtypes, atrial fibrillation (AF), and coronary heart disease (CHD). METHODS: We modelled 5-year UACR trajectories in 5,581 participants (mean age 61.7 years) from the Multi-Ethnic Study of Atherosclerosis using latent class mixed modelling across baseline, Exam 2, and Exam 3 (2000-2005). A separate sample of 4,343 participants with UACR measured at baseline, Exam 5, and at least one intermediate exam (2000-2012) was used for 10-year trajectory modelling. Cox proportional hazards models were used to assess associations between UACR trajectories and clinical endpoints. Linear regression analyses examined associations between UACR trajectories and N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TnT), as well as myocardial fibrosis assessed by cardiac MRI T1 mapping. RESULTS: Three distinct trajectory groups were identified for each time window. In the 5-year model, the "sustained medium to high" group, and in the 10-year model, the "rapid rise" group (each ∼8%) had 1.5- to 3.7-fold higher risks of HF, HF subtypes, composite of HF/death, AF, and CHD. Most of these associations were independent of baseline UACR levels and remained significant even among individuals with normoalbuminuria at baseline. After censoring for interim AF or CHD, associations persisted for HF and HFpEF, but not HFrEF. These groups also exhibited elevated NT-proBNP, hs-TnT, native T1, and extracellular volume fraction. CONCLUSION: Progressive UACR increases identify individuals at elevated cardiovascular risk, particularly for HF. Albuminuria is an early marker of glomerular injury and is associated with increased cardiovascular risk, even at levels below the clinical threshold. Most previous studies have relied on a single urine albumin-creatinine ratio (UACR) measurement. Using latent class mixed modelling, this study examined whether longitudinal UACR trajectories over 5- and 10-year periods were associated with subclinical and clinical heart failure (HF), HF subtypes, atrial fibrillation (AF), and coronary heart disease (CHD). Three distinct trajectory groups were identified: “slow rise at low level”, “slow rise at medium level”, and “sustained medium to high” (or “rapid rise” over 10 years). Distinct UACR trajectories identified two high-risk subgroups. In the 5-year analysis, participants with “sustained medium to high” UACR showed increased risks of HF, HF subtypes, AF, and CHD. In the 10-year analysis, those in the “rapid rise” class had similarly elevated risks. About 30% to 40% of these participants were normoalbuminuric at baseline but developed elevated UACR over time. After censoring for interim AF or CHD, associations remained significant for HF and HFpEF, but not for HFrEF. These findings were largely independent of baseline UACR.Individuals with persistently moderate to high and rapidly rising UACR levels showed parallel increases in cardiac biomarkers (N-terminal pro-brain natriuretic peptide and high-sensitivity troponin T) and a higher burden of interstitial myocardial fibrosis as assessed by T1 mapping, respectively.