Illusion of revascularization: does anyone achieve optimal revascularization during percutaneous coronary intervention?

This Perspective article is a form of 'pastiche', inspired by the 1993 review by Lincoff and Topol entitled 'Illusion of reperfusion', and explores how their concept continues to apply to percutaneous revascularization in patients with coronary artery disease and ischaemia. Just as Lincoff and Topol argued that reperfusion of acute myocardial infarction was facing unresolved obstacles that hampered clinical success in 1993, we propose that challenging issues are similarly jeopardizing the potential benefits of stent-based angioplasty today. By analysing the appropriateness and efficacy of percutaneous coronary intervention (PCI), we emphasize the limitations of relying solely on visual angiographic guidance, which frequently leads to inappropriate stenting and overtreatment in up to one-third of patients and the associated increased risk of periprocedural myocardial infarction. The lack of optimal revascularization observed in half of patients undergoing PCI confers risks such as suboptimal physiology after PCI, residual angina and long-term stent-related events, leaving an estimated 76% of patients with an 'illusion of revascularization'. These outcomes highlight the need to refine our diagnostic tools by integrating physiological assessments with targeted intracoronary imaging and emerging strategies, such as co-registration systems and angiography-based computational methods enhanced by artificial intelligence, to achieve optimal revascularization outcomes.

Angiographic Characteristics and Clinical Outcomes in Patients With Chronic Kidney Disease Undergoing Impella-Supported High-Risk Percutaneous Coronary Intervention: Insights From the cVAD PROTECT III Study.

BACKGROUND: Prior studies have found that patients with chronic kidney disease (CKD) have worse outcomes following percutaneous coronary intervention (PCI). There are no data about patients with advanced CKD undergoing Impella-supported high-risk PCI. We, therefore, aimed to evaluate angiographic characteristics and clinical outcomes in patients with CKD who received Impella-supported high-risk PCI as part of the catheter-based ventricular assist device PROTECT III study (A Prospective, Multi-Center, Randomized Controlled Trial of the IMPELLA RECOVER LP 2.5 System Versus Intra Aortic Balloon Pump [IABP] in Patients Undergoing Non Emergent High Risk PCI). METHODS: Patients enrolled in the PROTECT III study were analyzed according to their baseline estimated glomerular filtration rate (eGFR). The primary outcome was 90-day major adverse cardiovascular and cerebrovascular events (the composite of all-cause death, myocardial infarction, stroke/transient ischemic attack, and repeat revascularization). RESULTS: Of 1237 enrolled patients, 1052 patients with complete eGFR baseline assessment were evaluated: 586 with eGFR ≥60 mL/min per 1.73 m2, 190 with eGFR ≥45 to <60, 105 with eGFR ≥30 to <45, and 171 with eGFR <30 or on dialysis. Patients with lower eGFR (all groups with eGFR <60) were more frequently females and had a higher prevalence of hypertension, diabetes, anemia, and peripheral artery disease. The baseline Synergy Between PCI With Taxus and Cardiac Surgery score was similar between groups (28.2±12.6 for all groups). Patients with lower eGFR were more likely to have severe coronary calcifications and higher usage of atherectomy. There were no differences in individual PCI-related coronary complications between groups, but the rates of overall PCI complications were less frequent among patients with lower eGFR. Major adverse cardiovascular and cerebrovascular events at 90 days and 1-year mortality were significantly higher among patients with eGFR <30 mL/min per 1.73 m2 or on dialysis. CONCLUSIONS: Patients with advanced CKD undergoing Impella-assisted high-risk PCI tend to have higher baseline comorbidities, severe coronary calcification, and higher atherectomy usage, yet CKD was not associated with a higher rate of immediate PCI-related complications. However, 90-day major adverse cardiovascular and cerebrovascular events and 1-year mortality were significantly higher among patients with eGFR<30 mL/min per 1.73 m2 or on dialysis. Future studies of strategies to improve intermediate and long-term outcomes of these high-risk patients are warranted. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04136392.

Long-Term Percutaneous Coronary Intervention Outcomes in Chronic Versus Acute Coronary Syndromes (TARGET All Comers Trial).

In the Targeted therapy with a localised abluminal coated, low-dose sirolimus-eluting, biodegreadable polymer coronary stent (TARGET; NCT02520180) All Comers trial the biodegradable polymer (BP) sirolimus-eluting FIREHAWK stent was noninferior to the durable polymer (DP) everolimus-eluting XIENCE stent with respect to target lesion failure (TLF) at 1 and 5 years; however, the long-term safety and efficacy in the setting of acute coronary syndromes (ACS) are not known. We sought to assess the long-term outcomes in ACS versus chronic coronary syndromes (CCS) with BP sirolimus-eluting stent (SES) versus DP everolimus-eluting stent (EES). The TARGET AC study was a multicenter, open-label, noninferiority trial of all comer patients randomly allocated 1:1 to BP SES or DP EES (stratified by ST-elevation myocardial infarction and study site). In this predefined substudy, the outcomes were compared based on clinical presentation (ACS vs CCS) and treatment allocation. A total of 1,653 patients were enrolled (728 with ACS and 922 with CCS), with 94% completing the 5-year follow-up. The baseline characteristics were well-matched between the 2 stent types; however, co-morbidities were more prevalent in the CCS than in the ACS population. TLF (15.5% vs 17.7%, p = 0.24), patient-oriented outcomes (32.0% vs 34.4%, p = 0.31), and stent thrombosis (4.1% vs 3.3%, p = 0.40) were similar between patients with ACS and patients with CCS. In the ACS cohort, the outcomes at 5 years for BP SES versus DP EES were similar for TLF (16.0% vs 14.9%, p = 0.70), ischemia-driven target lesion revascularization (5.6% vs 8.3%, p = 0.17), and definite/probable stent thrombosis (2.7% vs 4.6%, p = 0.18). The same was true for the CCS cohort, with 5-year outcomes for BP SES versus DP EES for TLF (18.0% vs 17.4%, p = 0.82), ischemia-driven target lesion revascularization (6.4% vs 5.0%, p = 0.37), and definite/probable stent thrombosis (3.0% vs 1.8%, p = 0.26). In conclusion, in the TARGET AC trial, 1 in 3 patients had a major adverse event at 5 years, irrespective of CCS or ACS presentation. Long-term, the BP sirolimus-eluting FIREHAWK stent was as safe and effective as the DP everolimus-eluting XIENCE stent across the spectrum of clinical presentations.

Approval, Evidence, and "Off-Label" Device Utilization: The Patent Foramen Ovale Closure Story.

BACKGROUND: Following regulatory approval, medical devices may be used "off-label." Patent foramen ovale (PFO) closure is indicated to reduce recurrent stroke but has been proposed for other indications, including migraine, transient ischemic attack, and diving decompression illness. We sought to evaluate PFO closure rates and indications relative to the timing of regulatory approval and publication of key randomized trials. METHODS: We performed a retrospective cohort study using the OptumLabs Data Warehouse of US commercial insurance enrollees from 2006 to 2019. We quantified PFO closure among individuals with ≥2 years of preprocedure coverage to establish indications, classified hierarchically as stroke/systemic embolism, migraine, transient ischemia attack, or other. RESULTS: We identified 5315 patients undergoing PFO closure (51.8% female, 29.2%≥60 years old), which increased from 4.75 per 100 000 person-years in 2006 to 6.60 per 100 000 person-years in 2019. Patients aged ≥60 years accounted for 29.2% of closures. Procedure volumes corresponded weakly with supportive clinical publications and device approval. Among patients with PFO closure, 58.6% underwent closure for stroke/systemic embolism, 10.2% for transient ischemia attack, 8.8% for migraine, and 22.4% for other indications; 17.6% of patients had atrial fibrillation at baseline; and 11.9% developed atrial fibrillation postprocedure. Those aged ≥60 years and male were less likely to undergo closure for migraine than stroke/systemic embolism. CONCLUSIONS: From 2006 to 2019, PFO closure use was consistently low and corresponded weakly with clinical trial publications and regulatory status. Nearly half of patients underwent PFO closure for indications unapproved by the Food and Drug Administration. Regulators and payers should coordinate mechanisms to promote utilization for approved indications to ensure patient safety and should facilitate clinical trials for other possible indications.

Intravascular Imaging-Guided Versus Angiography-Guided Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis of Randomized Trials.

BACKGROUND: Despite the initial evidence supporting the utility of intravascular imaging to guide percutaneous coronary intervention (PCI), adoption remains low. Recent new trial data have become available. An updated study-level meta-analysis comparing intravascular imaging to angiography to guide PCI was performed. This study aimed to evaluate the clinical outcomes of intravascular imaging-guided PCI compared with angiography-guided PCI. METHODS AND RESULTS: A random-effects meta-analysis was performed on the basis of the intention-to-treat principle. The primary outcomes were major adverse cardiac events, cardiac death, and all-cause death. Mixed-effects meta-regression was performed to investigate the impact of complex PCI on the primary outcomes. A total of 16 trials with 7814 patients were included. The weighted mean follow-up duration was 28.8 months. Intravascular imaging led to a lower risk of major adverse cardiac events (relative risk [RR], 0.67 [95% CI, 0.55-0.82]; P<0.001), cardiac death (RR, 0.49 [95% CI, 0.34-0.71]; P<0.001), stent thrombosis (RR, 0.63 [95% CI, 0.40-0.99]; P=0.046), target-lesion revascularization (RR, 0.67 [95% CI, 0.49-0.91]; P=0.01), and target-vessel revascularization (RR, 0.60 [95% CI, 0.45-0.80]; P<0.001). In complex lesion subsets, the point estimate for imaging-guided PCI compared with angiography-guided PCI for all-cause death was a RR of 0.75 (95% CI, 0.55-1.02; P=0.07). CONCLUSIONS: In patients undergoing PCI, intravascular imaging is associated with reductions in major adverse cardiac events, cardiac death, stent thrombosis, target-lesion revascularization, and target-vessel revascularization. The magnitude of benefit is large and consistent across all included studies. There may also be benefits in all-cause death, particularly in complex lesion subsets. These results support the use of intravascular imaging as standard of care and updates of clinical guidelines.

Impact of sex on Transcatheter aortic valve replacement outcomes: Results of a single-center study.

BACKGROUND: Early studies on transcatheter aortic valve replacement (TAVR) outcomes showed that female sex was associated with better survival. With increased use of new-generation valves, the impact of sex on contemporary TAVR outcomes is less well known. METHODS: Retrospective analysis using institutional National Cardiovascular Data Registry STS/ACC TVT data was performed on all patients undergoing TAVR at Yale New Haven Hospital from July 2012 to August 2019. New-generation valves were Evolut PRO, Evolut R, and SAPIEN 3. Old-generation valves were CoreValve, SAPIEN, and SAPIEN XT. Log-rank test and Kaplan-Meier curves were used to compare sex differences in survival up to 1 year after TAVR. Cox modeling was used to adjust for baseline and procedural characteristic differences. RESULTS: 927 consecutive patients (41.4% women) underwent TAVR. Women were older (82.8 vs 80.6 years old; p < 0.001) with higher STS mortality scores compared with men (7.6% vs 6.4%; p < 0.001) despite lower prevalence of cardiovascular comorbidities including coronary artery disease, peripheral artery disease, and smoking. Most cases used transfemoral access (90.5%) and new-generation devices (72.3%). Women received smaller valves compared with men (20-26 mm: 78.0% vs 32.9%; 29-34 mm: 22.1% vs 67.1%; overall p < 0.0001). There were no statistically significant differences between sexes in both unadjusted and adjusted 1-year mortality. CONCLUSION: Our data show no significant difference in 1-year survival between sexes using primarily new generation valves. Further studies should reassess the impact of sex on TAVR outcomes and whether newer technologies like new valve design and sizes, and CT imaging may have eliminated sex-based disparities.

Effect of antecedent statin usage on conduction disturbances and arrhythmias after transcatheter aortic valve replacement.

BACKGROUND: Post-transcatheter aortic valve replacement (TAVR) conduction disturbances and atrial fibrillation (AF) are associated with markedly worse short- and long-term prognosis. Statins have multiple pleotropic effects that may be beneficial in mitigating the risk of these procedural complications as has been found for various other cardiac procedures and surgeries. METHODS: Data were retrospectively collected on consecutive patients in the Yale New Haven Health TAVR Registry who did not have a prior pacemaker, had at least 1 pre- and post-TAVR electrocardiogram, and did not have a change to their statin regimen during the index hospitalization. The primary endpoint was the composite of new pacemaker placement, new AF, and other new conduction disturbances evaluated at 7 days post-TAVR. RESULTS: Between, July 2012 and August 2019, 612 patients met inclusion criteria. Of these, 162 patients were not on antecedent statins, and 450 were (28 low-intensity, 225 moderate-intensity, and 197 high-intensity). After 1:1 propensity matching, 99 patients on moderate-/high-intensity statins were matched to 99 patients not on antecedent statins. At 7 days, there was no significant difference in the occurrence of the primary endpoint (57 % statin users vs 46 % non-statin users; p = 0.16). There was a trend toward increased conduction disturbances 7 days after TAVR in statin users (56 % vs 42 %; p = 0.07), but rates of AF (5 % vs 8 %; p = 0.39) and pacemaker placement (9 % vs 15 %; p = 0.20) were numerically lower in statin users. There was no significant difference in persistent conduction disturbances (21 % vs 18 %; p = 0.59). CONCLUSIONS: Statins do not appear to reduce the risk of post-TAVR AF or conduction abnormalities in this small retrospective study.

Sex-specific analysis of intravascular lithotripsy for peripheral artery disease from the Disrupt PAD III observational study.

OBJECTIVE: Endovascular therapy of lower extremity peripheral artery disease (PAD) is associated with higher complication rates and worse outcomes in women vs men. Although intravascular lithotripsy (IVL) has shown similarly favorable outcomes in men and women in calcified coronary arteries, there is no published safety and effectiveness data of peripheral IVL differentiated by sex. This study aims to evaluate sex-specific acute procedural safety and effectiveness following IVL treatment of calcified PAD. METHODS: We performed a secondary analysis of the multicenter Disrupt PAD III Observational Study, which assessed short-term procedural outcomes of patients undergoing treatment of symptomatic calcified lower extremity PAD with the Shockwave peripheral IVL system. Adjudicated acute safety and efficacy outcomes were compared by sex using univariate analysis performed with the χ2 test or Fisher exact test, as appropriate. RESULTS: A total of 1262 patients (29.9% women) were included, with >85% having moderate to severe lesion calcification. Women were older (74 vs 71 years; P < .001), had lower ankle-brachial index (0.7 vs 0.8; P = .003), smaller reference vessel size (5.3 vs 5.6 mm; P = .009), and more severe stenosis at baseline vs men (82.3% vs 79.8%; P = .012). Rates of diabetes, renal insufficiency, chronic limb-threatening ischemia, lesion length, and atherectomy use were similar in both groups. Residual stenosis after IVL alone was significantly reduced in both groups. Final residual stenosis was 21.9% in women and 24.7% in men (P = .001). Serious angiographic complications were infrequent and similar in both groups (1.4% vs 0.6%; P = .21), with no abrupt vessel closure, distal embolization, or thrombotic events during any procedure. CONCLUSIONS: The use of IVL to treat calcified PAD in this observational registry demonstrated favorable acute safety and effectiveness in both women and men.

Influence of left ventricular ejection fraction in patients undergoing contemporary pLVAD-supported high-risk PCI.

BACKGROUND: Left ventricular (LV) systolic dysfunction worsens outcomes in patients undergoing percutaneous coronary intervention (PCI). The objective of this study, therefore, was to evaluate outcomes of pLVAD-supported high-risk PCI (HRPCI) patients according to LV ejection fraction (LVEF). METHODS: Patients from the PROTECT III study undergoing pLVAD-supported HRPCI were stratified according to baseline LVEF: severe LV dysfunction (LVEF <30%), mild and moderate LV dysfunction (LVEF ≥30% to <50%), or preserved LV function (LVEF ≥50%). Major adverse cardiovascular and cerebrovascular events (MACCE: composite of all-cause death, myocardial infarction, stroke/transient ischemic attack, and repeat revascularization), and PCI-related complications were assessed at 90 days and mortality was assessed at 1-year. RESULTS: From March 2017 to March 2020, 940 patients had evaluable baseline LVEF recorded in the study database. Patients with preserved LV function were older, more frequently presented with myocardial infarction, and underwent more left main PCI and atherectomy. Immediate PCI-related coronary complications were infrequent (2.7%, overall), similar between groups (P = 0.98), and not associated with LVEF. Unadjusted 90-day MACCE rates were similar among LVEF groups; however, as a continuous variable, LVEF was associated with both 90-day MACCE (adj.HR per 5% 0.89, 95% CI [0.80, 0.98], P = 0.018) and 1-year mortality (adj.HR per 5% 0.84 [0.78, 0.90], P <0.0001). CONCLUSIONS: Patients who underwent pLVAD-supported HRPCI exhibited low incidence of PCI-related complications, regardless of baseline LVEF. However, LVEF was associated with 90-day MACCE and 1-year mortality.

Stroke reduction by cerebral embolic protection devices in transcatheter aortic valve implantation: a systematic review and Bayesian meta-analysis.

OBJECTIVES: The use of cerebral embolic protection (CEP) during transcatheter aortic valve implantation (TAVI) has been studied in several randomised trials. We aimed to perform a systematic review and Bayesian meta-analysis of randomised CEP trials, focusing on a clinically relevant reduction in disabling stroke. METHODS: A systematic search was applied to three electronic databases, including trials that randomised TAVI patients to CEP versus standard treatment. The primary outcome was the risk of disabling stroke. Outcomes were presented as relative risk (RR), absolute risk differences (ARDs), numbers needed to treat (NNTs) and the 95% credible intervals (CrIs). The minimal clinically important difference was determined at 1.1% ARD, per expert consensus (NNT 91). The principal Bayesian meta-analysis was performed under a vague prior, and secondary analyses were performed under two informed literature-based priors. RESULTS: Seven randomised studies were included for meta-analysis (n=3996: CEP n=2126, control n=1870). Under a vague prior, the estimated median RR of CEP use for disabling stroke was 0.56 (95% CrI 0.28 to 1.19, derived ARD 0.56% and NNT 179, I2=0%). Although the estimated posterior probability of any benefit was 94.4%, the probability of a clinically relevant effect was 0-0.1% under the vague and informed literature-based priors. Results were robust across multiple sensitivity analyses. CONCLUSION: There is a high probability of a beneficial CEP treatment effect, but this is unlikely to be clinically relevant. These findings suggest that future trials should focus on identifying TAVI patients with an increased baseline risk of stroke, and on the development of new generation devices. PROSPERO REGISTRATION NUMBER: CRD42023407006.

Targeted therapy with a localised abluminal groove, low-dose sirolimus-eluting, biodegradable-polymer coronary stent - five-year results of the TARGET All Comers randomised clinical trial.

BACKGROUND: In the prospective, multicentre, randomised TARGET All Comers study, percutaneous coronary intervention (PCI) with the FIREHAWK biodegradable-polymer sirolimus-eluting stent (BP-SES) was non-inferior to the durable-polymer everolimus-eluting stent (DP-EES) for the primary endpoint of target lesion failure (TLF) at 12 months. AIMS: We aimed to report the final study outcomes at 5 years. METHODS: Patients referred for PCI were randomised to receive either a BP-SES or DP-EES in a 1:1 ratio in 10 European countries. Randomisation was stratified by centre and ST-elevation myocardial infarction (STEMI) presentation, and clinical follow-up extended to 5 years. The primary endpoint was TLF (composite of cardiac death, target vessel myocardial infarction [MI], or ischaemia-driven target lesion revascularisation). Secondary endpoints included patient-oriented composite events (POCE; composite of all-cause death, all MI, or any revascularisation and its components). RESULTS: From December 2015 to October 2016, 1,653 patients were randomly assigned to the BP-SES or DP-EES groups, of which 93.8% completed 5-year clinical follow-up or were deceased. At 5 years, TLF occurred in 17.1% of the BP-SES group and in 16.3% of the DP-EES group (p=0.68). POCE occurred in 34.0% of the BP-SES group and 32.7% of the DP-EES group (p=0.58). Revascularisation was the most common POCE, occurring in 19.3% of patients receiving BP-SES and 19.2% receiving DP-EES, of which less than one-third was ischaemia-driven target lesion-related. In the landmark analysis, there were no differences in the rates of TLF and POCE between groups from 1 to 5 years, and these results were consistent across all subgroups. CONCLUSIONS: In an all-comers population requiring stent implantation for myocardial ischaemia, the BP-SES was non-inferior to the DP-EES for the primary endpoint of TLF at 12 months, and results were sustained at 5 years, confirming the long-term safety and efficacy of the FIREHAWK BP-SES.

Predictors of Cerebral Embolic Debris During Transcatheter Aortic Valve Replacement: The SafePass 2 First-in-Human Study.

Transcatheter aortic valve replacement (TAVR) generates significant debris, and strategies to mitigate cerebral embolization are needed. The novel Emboliner embolic protection catheter (Emboline, Inc., Santa Cruz, California) is designed to capture all particles generated during TAVR. This first-in-human study sought to assess the safety and feasibility of the device and to characterize the distribution and histopathology of the debris generated during TAVR. The SafePass 2 study was a prospective, nonrandomized, multicenter, single-arm investigation of the Emboliner device. Primary end points included 30-day major adverse cardiac and cerebrovascular events (MACCE) and technical performance. Computed tomography angiography was analyzed by an independent core laboratory, and filters were sent for histopathology of captured debris. Predictors of particle number were identified using >150 µm and >500 µm size thresholds. Of 31 subjects enrolled, technical success was 100%, and 30-day MACCE was 6.5% (2 cerebrovascular accidents, with 1 attributed to subtherapeutic dosing of rivaroxaban along with atrial fibrillation and the other to possible previous small ischemic strokes on magnetic resonance imaging; neither MACCE event had a causal relation to the Emboliner). All filters contained debris, with a median of 191.0 particles >150 µm and 14.0 particles >500 µm. Histopathology revealed mostly acute thrombus and valve or arterial tissue with lesser amounts of calcified tissue. A history of atrial fibrillation predicted a greater number of particles >500 µm (p = 0.0259) and its presence on admission was associated with 4.1 times more particles >150 µm (p = 0.0130) and 8.1 times more particles >500 µm (p = 0.0086). Self-expanding valves were associated with twice the number of particles >150 µm (p = 0.0281). TASK score was positively correlated with number of particles >500 µm (p = 0.0337). The Emboliner device was safe and feasible. Emboli after TAVR appear more numerous than previously documented. Atrial fibrillation, higher TASK score, and self-expanding valve use conferred higher embolic burden. Notably, none of the tested computed tomography angiography features were able to identify with higher embolic risk. Larger-scale studies are needed to identify high-risk patients for selective embolic protection device use.

Cerebral embolic protection during transcatheter heart interventions.

Stroke remains a devastating complication of transcatheter aortic valve replacement (TAVR), with the incidence of clinically apparent stroke seemingly fixed at around 3% despite TAVR's significant evolution during the past decade. Embolic showers of debris (calcium, atheroma, valve material, foreign material) are captured in the majority of patients who have TAVR using a filter-based cerebral embolic protection device (CEPD). Additionally, in systematic brain imaging studies, the majority of patients receiving TAVR exhibit new cerebral lesions. Mechanistic studies have shown reductions in the volume of new cerebral lesions using CEPDs, yet the first randomised trial powered for periprocedural stroke within 72 hours of a transfemoral TAVR failed to meet its primary endpoint of showing superiority of the SENTINEL CEPD. The present review summarises the clinicopathological rationale for the development of CEPDs, the evidence behind these devices to date and the emerging recognition of cerebral embolisation in many non-TAVR transcatheter procedures. Given the uniqueness of each of the various CEPDs under development, specific trials tailored to their designs will need to be undertaken to broaden the CEPD field, in addition to evaluating the role of CEPD in non-TAVR transcatheter heart interventions. Importantly, the cost-effectiveness of these devices will require assessment to broaden the adoption of CEPDs globally.

Sex Differences in pLVAD-Assisted High-Risk Percutaneous Coronary Intervention: Insights From the PROTECT III Study.

BACKGROUND: Prior studies have found that female patients have worse outcomes following high-risk percutaneous coronary intervention (HRPCI). OBJECTIVES: The authors sought to evaluate sex-based differences in patient and procedural characteristics, clinical outcomes, and safety of Impella-supported HRPCI in the PROTECT III study. METHODS: We evaluated sex-based differences in the PROTECT III study; a prospective, multicenter, observational study of patients undergoing Impella-supported HRPCI. The primary outcome was 90-day major adverse cardiac and cerebrovascular events (MACCE)-the composite of all-cause death, myocardial infarction, stroke/transient ischemic attack, and repeat revascularization. RESULTS: From March 2017 to March 2020, 1,237 patients (27% female) were enrolled. Female patients were older, more often Black, more often anemic, and had more prior strokes and worse renal function, but higher ejection fractions compared to male patients. Preprocedural SYNTAX score was similar between sexes (28.0 ± 12.3). Female patients were more likely to present with acute myocardial infarction (40.7% vs 33.2%; P = 0.02) and more often had femoral access used for PCI and nonfemoral access used for Impella device implantation. Female patients had higher rates of immediate PCI-related coronary complications (4.2% vs 2.1%; P = 0.004) and a greater drop in SYNTAX score post-procedure (-22.6 vs -21.0; P = 0.04). There were no sex differences in 90-day MACCE, vascular complications requiring surgery, major bleeding, or acute limb ischemia. After adjustment using propensity matching and multivariable regression, immediate PCI-related complications was the only safety or clinical outcome that was significantly different by sex. CONCLUSIONS: In this study, rates of 90-day MACCE compared favorably to prior cohorts of HRPCI patients and there was no significant sex differences. (The PROTECT III Study is a substudy of The Global cVAD Study [cVAD]; NCT04136392).

Impact of New-Onset Conduction Disturbances following Transcatheter Aortic Valve Replacement on Outcomes: A Single-Center Study.

Background: Transcatheter aortic valve replacement (TAVR) is known to increase the incidence of conduction disturbances compared to surgical aortic valve replacement; however, there are limited data on the impact and duration of these conduction disturbances on longer term outcomes. Objective: To determine the differential impact of persistent versus nonpersistent new-onset conduction disturbances on TAVR-related complications and outcomes. Methods: This is a single-center retrospective analysis of 927 consecutive patients with aortic stenosis who underwent TAVR at Yale New Haven Hospital from July 2012 to August 2019. Patients with new-onset conduction disturbances within 7 days following TAVR were selected for this study. Persistent and nonpersistent disturbances were, respectively, defined as persisting or not persisting on all patient ECGs for up to 1.5 years after TAVR or until death. Results: Within 7 days after TAVR, conduction disturbances occurred in 42.3% (392/927) of the patients. Conduction disturbances persisted in 150 (38%) patients and did not persist in 187 (48%) patients, and 55 (14%) patients were excluded for having mixed (both persistent and nonpersistent) disturbances. Compared with nonpersistent disturbances, patients with persistent disturbances were more likely to receive a PPM within 7 days after the TAVR procedure (46.0% versus 4.3%, p < 0.001) and had a greater unadjusted 1-year cardiac-related and all-cause mortality risk (HR 2.54, p=0.044 and HR 1.90, p=0.046, respectively). Conclusion: Persistent conduction disturbances were associated with a greater cardiac and all-cause mortality rate at one year following TAVR. Future research should investigate periprocedural factors to reduce persistent conduction disturbances and outcomes beyond one year follow-up.

Chocolate Touch Versus Lutonix Drug-Coated Balloon for Femoropopliteal Lesions in Diabetes: The Chocolate Touch Study.

BACKGROUND: The randomized Chocolate Touch Study demonstrated that in patients undergoing treatment of femoropopliteal artery lesions, the Chocolate Touch drug-coated balloon (DCB) was safe and had superior efficacy at 12 months compared with the Lutonix DCB. We report the prespecified diabetes subanalysis comparing outcomes among patients with and without diabetes mellitus (DM). METHODS: Patients with claudication or ischemic rest pain (Rutherford class 2-4) were randomized to Chocolate Touch or Lutonix DCB. The primary efficacy endpoint was DCB success defined as primary patency at 12 months (peak systolic velocity ratio <2.4 by duplex ultrasound without clinically driven target lesion revascularization in the absence of bailout stenting). The primary safety endpoint was freedom from major adverse events at 12 months, a composite of target limb-related death, major amputation, or reintervention. RESULTS: A total of 313 patients (38% DM [n=119]) were randomized to either Chocolate Touch (n=66/152) or Lutonix DCB (n=53/161). Among patients with DM, DCB success was 77.2% and 60.5% (p=0.08), and in non-DM patients, DCB success was 80% and 71.3% (p=0.2114) for the Chocolate Touch and Lutonix DCB, respectively. The primary safety endpoint was similar for both cohorts regardless of DM status (interaction test, p=0.96). CONCLUSIONS: This randomized trial demonstrated similar safety and efficacy for the treatment of femoropopliteal disease with the Chocolate Touch DCB compared with using the Lutonix DCB regardless of DM status at 12 months. CLINICAL IMPACT: This substudy of the Chocolate Touch Study demonstrated similar safety and efficacy for treatment of femoropopliteal disease of the Chocolate Touch DCB compared with the Lutonix DCB regardless of diabetes (DM) status at 12 months. Endovascular therapy has become the therapy of choice for the treatment of most symptomatic femoropopliteal lesions regardless of DM status. These results give clinicians another option when treating femoropopliteal disease in this high-risk patient population.

Effects of Elective Coronary Revascularization vs Medical Therapy Alone on Noncardiac Mortality: A Meta-Analysis.

BACKGROUND: Uncertainty exists whether coronary revascularization plus medical therapy (MT) is associated with an increase in noncardiac mortality in chronic coronary syndrome (CCS) when compared with MT alone, particularly following recent data from the ISCHEMIA-EXTEND (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial. OBJECTIVES: This study conducted a large-scale meta-analysis of trials comparing elective coronary revascularization plus MT vs MT alone in patients with CCS to determine whether revascularization has a differential impact on noncardiac mortality at the longest follow-up. METHODS: We searched for randomized trials comparing revascularization plus MT vs MT alone in patients with CCS. Treatment effects were measured by rate ratios (RRs) with 95% CIs, using random-effects models. Noncardiac mortality was the prespecified endpoint. The study is registered with PROSPERO (CRD42022380664). RESULTS: Eighteen trials were included involving 16,908 patients randomized to either revascularization plus MT (n = 8,665) or to MT alone (n = 8,243). No significant differences were detected in noncardiac mortality between the assigned treatment groups (RR: 1.09; 95% CI: 0.94-1.26; P = 0.26), with absent heterogeneity (I2 = 0%). Results were consistent without the ISCHEMIA trial (RR: 1.00; 95% CI: 0.84-1.18; P = 0.97). By meta-regression, follow-up duration did not affect noncardiac death rates with revascularization plus MT vs MT alone (P = 0.52). Trial sequential analysis confirmed the reliability of meta-analysis, with the cumulative Z-curve of trial evidence within the nonsignificance area and reaching futility boundaries. Bayesian meta-analysis findings were consistent with the standard approach (RR: 1.08; 95% credible interval: 0.90-1.31). CONCLUSIONS: In patients with CCS, noncardiac mortality in late follow-up was similar for revascularization plus MT compared with MT alone.