BACKGROUND: The relationship between the extent and severity of stress-induced ischemia and the extent and severity of anatomic coronary artery disease (CAD) in patients with obstructive CAD is multifactorial and includes the intensity of stress achieved, type of testing used, presence and extent of prior infarction, collateral blood flow, plaque characteristics, microvascular disease, coronary vasomotor tone, and genetic factors. Among chronic coronary disease participants with site-determined moderate or severe ischemia, we investigated associations between ischemia severity on stress testing and the extent of CAD on coronary computed tomography angiography. METHODS: Clinically indicated stress testing included nuclear imaging, echocardiography, cardiac magnetic resonance imaging, or nonimaging exercise tolerance test. Among those with preserved renal function who underwent coronary computed tomography angiography, we examined relationships between ischemia and CAD by coronary computed tomography angiography, overall, and by stress test modality, regardless of subsequent randomization. Core laboratories categorized ischemia as severe, moderate, mild, or none, while the extent and severity of anatomic CAD were categorized based on the modified Duke prognostic index. RESULTS: Among 3601 participants with interpretable stress tests and coronary computed tomography angiography, ischemia severity was weakly associated with CAD extent/severity (r=0.27), with modest variability in strength of association by modality: nuclear (n=1532; r=0.40), echocardiography (n=827; r=0.15), cardiac magnetic resonance imaging (n=108; r=0.31), and exercise tolerance test (n=1134; r=0.18). The extent of infarction on nuclear imaging and echocardiography was weakly associated with CAD extent/severity. CONCLUSIONS: Overall, ischemia severity on stress testing showed weak to moderate associations with the anatomic extent of CAD in this cohort with moderate or severe ischemia on local interpretation and controlled symptoms. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01471522.

Background: Evidence is limited as to whether outcomes differ between patients with tricuspid regurgitation (TR) treated with tricuspid transcatheter edge-to-edge repair (T-TEER) versus surgical tricuspid valve repair. We aimed to compare outcomes between these two approaches. Methods: We analyzed the data on Medicare fee-for-service beneficiaries aged 65 to 99 with TR who underwent T-TEER or isolated surgical repair between July 2016 and December 2020. The primary outcome was two-year all-cause mortality. Other outcomes included in-hospital mortality and permanent pacemaker implantation as well as two-year heart failure hospitalization and tricuspid valve reintervention. A propensity score matching weight analysis was used to adjust for potential confounders. Results: A total of 1,143 patients were included (409 T-TEER versus 734 surgery). The proportion of T-TEER cases increased from 2% in the third quarter of 2016 to 67% in the last quarter of 2020 among all isolated TR procedures. After adjustment for potential confounders, we found no evidence that two-year all-cause mortality differs between patients treated with T-TEER versus surgical repair (adjusted HR, 0.84; 95% CI, 0.63–1.13). Patients treated with T-TEER experienced lower in-hospital mortality (2.5% versus 12.5%, P<0.001) and permanent pacemaker implantation rates (0.0% versus 12.7%, P<0.001) than those treated by surgical repair. At two years, we found no differences in heart failure hospitalizations, but tricuspid valve reinterventions were more frequent in the T-TEER group (subdistribution HR, 8.03; 95% CI, 2.87–22.48). Conclusions: Among Medicare beneficiaries with TR, two-year mortality rate was comparable between T-TEER and surgical repair. T-TEER showed advantages in perioperative outcomes, including lower in-hospital mortality and pacemaker implantation rates, while tricuspid valve reinterventions were more frequent in the T-TEER group. Further studies are necessary to refine indications, patient selections, and optimal timing for intervention with either treatment strategy.

XC001 is a novel adenoviral-5 vector designed to express multiple isoforms of VEGF (vascular endothelial growth factor) and more safely and potently induce angiogenesis. The EXACT trial (Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment) assessed the safety and preliminary efficacy of XC001 in patients with no option refractory angina. In this single-arm, multicenter, open-label trial, 32 patients with no option refractory angina received a single treatment of XC001 (1×1011 viral particles) via transepicardial delivery. There were no severe adverse events attributed to the study drug. Twenty expected severe adverse events in 13 patients were related to the surgical procedure. Total exercise duration increased from a mean±SD of 359.9±105.55 seconds at baseline to 448.2±168.45 (3 months), 449.2±175.9 (6 months), and 477.6±174.7 (12 months; +88.3 [95% CI, 37.1-139.5], +84.5 [95% CI, 34.1-134.9], and +115.5 [95% CI, 59.1-171.9]). Total myocardial perfusion deficit on positron emission tomography imaging decreased by 10.2% (95% CI, -3.1% to 23.5%), 14.3% (95% CI, 2.8%-25.7%), and 10.2% (95% CI, -0.8% to -21.2%). Angina frequency decreased from a mean±SD 12.2±12.5 episodes to 5.2±7.2 (3 months), 5.1±7.8 (6 months), and 2.7±4.8 (12 months), with an average decrease of 7.7 (95% CI, 4.1-11.3), 6.6 (95% CI, 3.5-9.7), and 8.8 (4.6-13.0) episodes at 3, 6, and 12 months. Angina class improved in 81% of participants at 6 months. XC001 administered via transepicardial delivery is safe and generally well tolerated. Exploratory improvements in total exercise duration, ischemic burden, and subjective measures support a biologic effect sustained to 12 months, warranting further investigation. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04125732.

Drug-coated balloons (DCBs) are specialized coronary devices comprised of a semicompliant balloon catheter with an engineered coating that allows the delivery of antiproliferative agents locally to the vessel wall during percutaneous coronary intervention. Although DCBs were initially developed more than a decade ago, their potential in coronary interventions has recently sparked renewed interest, especially in the United States. Originally designed to overcome the limitations of conventional balloon angioplasty and stenting, they aim to match or even improve upon the outcomes of drug-eluting stents without leaving a permanent implant. Presently, in-stent restenosis is the condition with the most robust evidence supporting the use of DCBs. DCBs provide improved long-term vessel patency compared with conventional balloon angioplasty and may be comparable to drug-eluting stents without the need for an additional stent layer, supporting their use as a first-line therapy for in-stent restenosis. Beyond the treatment of in-stent restenosis, DCBs provide an additional tool for de novo lesions for a strategy that avoids a permanent metal scaffold, which may be especially useful for the management of technically challenging anatomies such as small vessels and bifurcations. DCBs might also be advantageous for patients with high bleeding risk due to the decreased necessity for extended antiplatelet therapy, and in patients with diabetes and patients with diffuse disease to minimize long-stented segments. Further studies are crucial to confirm these broader applications for DCBs and to further validate safety and efficacy.

The Murray law-based quantitative flow ratio (μFR) is an emerging technique that requires only 1 projection of coronary angiography with similar accuracy to quantitative flow ratio (QFR). However, it has not been validated for the evaluation of noninfarct-related artery (non-IRA) in acute myocardial infarction (AMI) settings. Therefore, our study aimed to evaluate the diagnostic accuracy of μFR and the safety of deferring non-IRA lesions with μFR >0.80 in the setting of AMI. μFR and QFR were analyzed for non-IRA lesions of patients with AMI enrolled in the FRAME-AMI trial (Fractional Flow Reserve Versus Angiography-Guided Strategy for Management of Non-Infarction Related Artery Stenosis in Patients With Acute Myocardial Infarction), consisting of fractional flow reserve (FFR)-guided percutaneous coronary intervention and angiography-guided percutaneous coronary intervention groups. The diagnostic accuracy of μFR was compared with QFR and FFR. Patients were classified by the non-IRA μFR value of 0.80 as a cutoff value. The primary outcome was a vessel-oriented composite outcome, a composite of cardiac death, non-IRA-related myocardial infarction, and non-IRA-related repeat revascularization. μFR and QFR analyses were feasible in 443 patients (552 lesions). μFR showed acceptable correlation with FFR (R=0.777; P<0.001), comparable C-index with QFR to predict FFR ≤0.80 (μFR versus QFR: 0.926 versus 0.961, P=0.070), and shorter total analysis time (mean, 32.7 versus 186.9 s; P<0.001). Non-IRA with μFR >0.80 and deferred percutaneous coronary intervention had a significantly lower risk of vessel-oriented composite outcome than non-IRA with performed percutaneous coronary intervention (3.4% versus 10.5%; hazard ratio, 0.37 [95% CI, 0.14-0.99]; P=0.048). In patients with multivessel AMI, μFR of non-IRA showed acceptable diagnostic accuracy comparable to that of QFR to predict FFR ≤0.80. Deferred non-IRA with μFR >0.80 showed a lower risk of vessel-oriented composite outcome than revascularized non-IRA. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02715518.

Anatomic selection for Harmony valve implant is determined with the aid of a screening report and perimeter plot (PP) that depicts the perimeter-derived radius along the right ventricular outflow tract (RVOT) and projects device oversizing. The PP provides an estimation of suitability for implant, but its sensitivity as a screening method is unknown. This study was performed to describe anatomic features and outcomes in patients who underwent Harmony TPV25 implant despite a PP that predicted inadequate oversizing. We reviewed RVOT anatomic features and measurements in patients who underwent transcatheter pulmonary valve replacement with the Harmony TPV25 device despite a PP that predicted inadequate oversizing. This study included 22 patients. There were no unsuccessful implants or adverse valve-related events. Anatomic features varied, but all patients fit into 1 of 3 anatomic types characterized by differences in RVOT dimensions. Type 1 patients (n=9) had a long RVOT with a choke point and a wide main pulmonary artery. Type 2 patients (n=6) had a short RVOT that was pyramidal in shape, with no choke point, and extensive main pulmonary artery lengthening/expansion during systole. Type 3 patients (n=7) had a short, bulbous main pulmonary artery with a choke point and an open pulmonary artery bifurcation. Transcatheter pulmonary valve replacement with the Harmony valve is feasible in some patients whose PP fit analysis predicts inadequate oversizing. All cases in this series fit into 1 of 3 anatomic patterns, which are not identified in the screening report. Implanters must review cases individually to assess the feasibility of the implant.