Daily Cardiology Research Analysis
Analyzed 186 papers and selected 3 impactful papers.
Summary
A 5-year follow-up of the FAVOR III China randomized trial shows that QFR-guided PCI yields durable reductions in myocardial infarction and repeat revascularization versus angiography guidance, with most benefit accruing within 2 years. A mechanistic study in Circulation identifies endothelial SHMT2 as a noncanonical driver of pulmonary hypertension through a SHMT2–RhoB axis, nominating a druggable target. A prospective JACC: Cardiovascular Interventions study introduces a CT-derived volumetric metric (VTCV) that improves prediction of coronary obstruction risk during TAVR and is externally validated.
Research Themes
- Physiology-guided coronary intervention and long-term outcomes
- Endothelial mechanisms driving pulmonary vascular remodeling
- CT-based procedural risk stratification for TAVR
Selected Articles
1. Angiographic Quantitative Flow Ratio-Guided Coronary Intervention: 5-Year Follow-Up From the FAVOR III China Randomized Trial.
In this multicenter randomized trial, QFR-guided PCI reduced 5-year MACE versus angiography guidance, driven by fewer myocardial infarctions and ischemia-driven revascularizations, while all-cause mortality was similar. Landmark analyses indicate benefits accrued mainly within the first 2 years.
Impact: Provides robust long-term randomized evidence that physiology-guided PCI improves outcomes beyond angiography guidance, informing contemporary revascularization strategy.
Clinical Implications: Adopting QFR guidance to defer PCI in non-ischemic lesions and treat only functionally significant stenoses can reduce MI and repeat revascularization, with most gains early; programs should prioritize physiology integration.
Key Findings
- QFR-guided PCI reduced 5-year MACE versus angiography guidance (17.5% vs 21.1%; HR 0.80).
- Lower rates of myocardial infarction (5.8% vs 9.0%; HR 0.63) and ischemia-driven revascularization (9.6% vs 12.0%; HR 0.78) drove the benefit.
- All-cause mortality was similar; benefits accrued predominantly within the first 2 years post-PCI.
Methodological Strengths
- Randomized, multicenter design with 5-year follow-up and clinically meaningful endpoints.
- Pre-specified landmark analysis clarifying temporal accrual of benefit.
Limitations
- All-cause mortality was not reduced, and benefits concentrated in the first 2 years.
- Generalizability beyond the trial population and healthcare context may be limited.
Future Directions: Evaluate implementation strategies, cost-effectiveness across health systems, and synergy with intravascular imaging; assess outcomes in complex subsets and global populations.
BACKGROUND: The multicenter, randomized, sham-controlled FAVOR III China trial (Comparison of Quantitative Flow Ratio-Guided and Angiography-Guided Percutaneous Intervention in Patients with Coronary Artery Disease) demonstrated that quantitative flow ratio (QFR)-guided percutaneous coronary intervention (PCI) resulted in better outcomes compared with angiographic guidance at 1-year and 2-year follow-up. Whether these benefits are sustained over long-term follow-up remains uncertain. OBJECTIVES: The purpose of this study was to evaluate the long-term effectiveness and safety of a QFR-guided PCI strategy compared with angiography-guided PCI at 5 years. METHODS: Patients with at least 1 angiographically intermediate coronary lesion (50%-90% diameter stenosis) in a vessel ≥2.5 mm diameter were randomized to a QFR-guided (PCI performed only if QFR ≤0.80) or angiography-guided strategy. The primary endpoint was major adverse cardiac events (a composite of all-cause death, myocardial infarction, or ischemia-driven revascularization) at 1 year; 5-year outcomes data are reported herein. RESULTS: At 5 years, major adverse cardiac events composite was lower with QFR guidance than with angiography guidance (17.5% vs 21.1%; HR: 0.80; 95% CI: 0.69-0.92; P = 0.002), driven by fewer myocardial infarctions (5.8% vs 9.0%; HR: 0.63; 95% CI: 0.49-0.80; P < 0.0001) and ischemia-driven revascularizations (9.6% vs 12.0%; HR: 0.78; 95% CI: 0.64-0.95; P = 0.02) in the QFR-guided group. All-cause death did not differ between groups. Landmark analysis showed that the benefit of QFR guidance accrued predominantly within the first 2 years (8.5% vs 12.5%; HR: 0.66; 95% CI: 0.54-0.81; P < 0.0001), with similar outcomes between 2 and 5 years (10.2% vs 11.2%; HR: 0.90; 95% CI: 0.73-1.11; P = 0.32; P for interaction = 0.001). CONCLUSIONS: Compared with angiography guidance, QFR-guided strategy improved 5-year clinical outcomes, with benefits primarily achieved within the first 2 years. (The FAVOR III China Study; NCT03656848).
2. Endothelial SHMT2 Drives Pulmonary Vascular Remodeling Through Noncanonical Pathway in Pulmonary Hypertension.
Across patient lungs and multiple rodent PH models, endothelial SHMT2 was upregulated and promoted pulmonary vascular remodeling via a noncanonical SHMT2–RhoB pathway. Endothelial-specific gene perturbation and a small-molecule inhibitor targeting SHMT2’s nonmetabolic function supported its therapeutic potential.
Impact: Reveals a previously unrecognized endothelial SHMT2–RhoB axis in PH pathogenesis, combining human tissues, multiple in vivo models, and targetable chemistry.
Clinical Implications: While preclinical, the data nominate endothelial SHMT2’s nonmetabolic function as a druggable node; future first-in-human studies could expand options beyond vasodilators by addressing vascular remodeling.
Key Findings
- Proteomics identified SHMT2 upregulation in hypoxia-treated human pulmonary artery endothelial cells; corroborated in PH patient lungs and rodent models.
- Endothelial-specific SHMT2 modulation altered pulmonary vascular remodeling in vivo.
- A virtual-screened small-molecule inhibitor targeting SHMT2’s nonmetabolic function showed therapeutic potential in rodent PH models, implicating a SHMT2–RhoB axis.
Methodological Strengths
- Translational pipeline spanning human tissue validation, multiple rodent PH models, and endothelial-specific genetic manipulation.
- Integration of virtual screening with in vivo testing of a small-molecule inhibitor.
Limitations
- Abstracted data suggest incomplete mechanistic details and truncated reporting; full effect sizes and safety of the inhibitor are not detailed.
- Clinical translation remains untested; human pharmacology and off-target effects are unknown.
Future Directions: Define the SHMT2–RhoB signaling cascade, optimize and profile inhibitors, and progress to first-in-human trials with vascular remodeling endpoints and right heart function.
BACKGROUND: Pulmonary hypertension (PH) is a progressive, life-threatening disease characterized primarily by pulmonary vascular remodeling in which endothelial dysfunction plays a vital role. However, the molecular factors contributing to this pathological process remain incompletely understood. Through proteomic analysis of hypoxia-treated human pulmonary artery endothelial cells, we identified serine hydroxymethyltransferase 2 (SHMT2) as a potential target in PH, but its role in disease pathogenesis and the underlying mechanisms remain unclear. METHODS: The expression and function of SHMT2 were assessed in lung samples from patients with PH and in rodent PH models, including hypoxia-exposed mice and monocrotaline- or Sugen 5416/hypoxia-induced rats. Endothelial cell-specific SHMT2 loss and gain of function were achieved by conditional knockout and adeno-associated virus 9-mediated gene modulation. In vitro studies were performed in hypoxia-treated human pulmonary artery endothelial cells and HEK-293T cells. Virtual screening was used to identify a small-molecule inhibitor targeting the nonmetabolic function of SHMT2, and its therapeutic potential was further evaluated in rodent PH models. RESULTS: SHMT2 was upregulated predominantly in pulmonary vascular endothelium of patients with PH and multiple rodent PH models. In vivo, endothelial cell-specific deletion of CONCLUSIONS: This study highlights endothelial SHMT2 as an important contributor to PH pathogenesis and reveals a noncanonical SHMT2-RhoB pathway that promotes endothelial dysfunction. Targeting this pathway may represent a potential therapeutic strategy for PH.
3. CT-Based Risk Stratification of Coronary Obstruction During TAVR: Clinical Utility and a New Volumetric Parameter.
In 164 TAVR candidates at CO risk, a novel CT-derived volumetric metric (VTCV) independently predicted coronary obstruction and outperformed VTC distance; all CO events occurred in the algorithm-defined high-risk category. External validation across 11 European centers supported VTCV’s predictive utility.
Impact: Introduces a practical, CT-derived volumetric predictor with external validation to refine preprocedural planning and coronary protection strategies in TAVR.
Clinical Implications: Preprocedural CT incorporating VTCV can better identify patients at prohibitive CO risk and guide selective coronary protection or alternative strategies (e.g., leaflet modification, device selection).
Key Findings
- All coronary obstruction events (n=7) occurred within the algorithm-defined high-risk category.
- The novel valve-to-coronary volume (VTCV) independently predicted coronary obstruction (AUC 0.841) and outperformed VTC distance.
- External validation across 11 European centers confirmed VTCV’s predictive value.
Methodological Strengths
- Prospective cohort with standardized CT-based risk stratification and VARC-3 endpoints.
- Introduction of a novel volumetric metric with external multicenter validation.
Limitations
- Single-center primary cohort with a small number of CO events may limit precision.
- Use of coronary protection was not randomized and may be influenced by unmeasured factors.
Future Directions: Prospective multicenter studies to define VTCV thresholds for decision-making, integrate with leaflet-modification algorithms, and test impacts on clinical outcomes.
BACKGROUND: Coronary obstruction (CO) during transcatheter aortic valve replacement (TAVR) is rare but potentially fatal. Computed tomography (CT)-based risk assessment algorithms aim to identify high-risk patients, but their utility remains underexplored. OBJECTIVES: The aim of this study was to examine the clinical utility of a CT-derived algorithm for predicting CO during TAVR and identify predictors of CO despite coronary protection (CP). METHODS: In this prospective study, 164 patients at risk for CO during TAVR were enrolled. Preprocedural CT was used to classify risk using a published algorithm. A novel volumetric parameter, valve-to-coronary volume (VTCV), was calculated in high-risk cases using sinus width and valve-to-coronary (VTC) distance. The decision to use CP was left to the heart team. Clinical endpoints followed Valve Academic Research Consortium 3 definitions. RESULTS: According to the CT-based algorithm, 58.5% of patients (96 of 164) were at low risk, 24.4% (40 of 164) at intermediate risk, and 17.1% (28 of 164) at high risk. CP was performed in 12.8% of low-risk patients (16 of 125), 52.8% of intermediate-risk patients (28 of 53), and 93.9% of high-risk patients (31 of 33). All CO events (n = 7) occurred in the high-risk group. VTC distance and VTCV were significantly lower in patients with CO (P = 0.006 and P = 0.005, respectively). VTCV independently predicted CO (area under the curve, 0.841; 95% CI: 0.702-0.979; P < 0.001), outperforming VTC distance alone. The predictive value of VTCV was validated in an external cohort including 11 European centers. CONCLUSIONS: A CT-based algorithm stratifies patients into 3 CO risk categories, though the decision for CP in clinical practice seems to incorporate additional clinical and procedural variables. Although CP reduces CO risk, its efficacy is limited in patients with very small VTCV, which can be predicted preprocedurally via CT. (Leipzig TAVR Registry; NCT05015452).