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Intravascular lithotripsy (IVL) uses acoustic shock waves in a balloon-based delivery system to modify severely calcified atherosclerotic coronary vascular lesions in preparation for stent implantation. IVL results in circumferential and longitudinal calcium fracture, which improves transmural vessel compliance and facilitates subsequent stent expansion without requiring high-pressure balloon dilation. Clinical trials have demonstrated IVL to be safe (low rates of major adverse cardiac events in hospital and to 1 year; low rates of severe angiographic complications), effective (high rates of procedural success), and easy to use (little or no learning curve) when applied in the treatment of severely calcified coronary arteries.

Background: Differences in patient characteristics, changes in treatment algorithms, and advances in medical technology could each influence the applicability of older randomized trial results to contemporary clinical practice. The DAPT Study (Dual Antiplatelet Therapy) found that longer-duration DAPT decreased ischemic events at the expense of greater bleeding, but subsequent evolution in stent technology and clinical practice may attenuate the benefit of prolonged DAPT in a contemporary population. We evaluated whether the DAPT Study population is different from a contemporary population of US patients receiving percutaneous coronary intervention and estimated the treatment effect of extended-duration antiplatelet therapy after percutaneous coronary intervention in this more contemporary cohort. Methods: We compared the characteristics of drug-eluting stent–treated patients randomly assigned in the DAPT Study to a sample of more contemporary drug-eluting stent–treated patients in the National Cardiovascular Data Registry CathPCI Registry from July 2016 to June 2017. After linking trial and registry data, we used inverse-odds of trial participation weighting to account for patient and procedural characteristics and estimated a contemporary real-world treatment effect of 30 versus 12 months of DAPT after coronary stent procedures. Results: The US drug-eluting stent–treated trial cohort included 8864 DAPT Study patients, and the registry cohort included 568 540 patients. Compared with the trial population, registry patients had more comorbidities and were more likely to present with myocardial infarction and receive 2nd-generation drug-eluting stents. After reweighting trial results to represent the registry population, there was no longer a significant effect of prolonged DAPT on reducing stent thrombosis (reweighted treatment effect: –0.40 [95% CI, –0.99% to 0.15%]), major adverse cardiac and cerebrovascular events (reweighted treatment effect, –0.52 [95% CI, –2.62% to 1.03%]), or myocardial infarction (reweighted treatment effect, –0.97% [95% CI, –2.75% to 0.18%]), but the increase in bleeding with prolonged DAPT persisted (reweighted treatment effect, 2.42% [95% CI, 0.79% to 3.91%]). Conclusions: The differences between the patients and devices used in contemporary clinical practice compared with the DAPT Study were associated with the attenuation of benefits and greater harms attributable to prolonged DAPT duration. These findings limit the applicability of the average treatment effects from the DAPT Study in modern clinical practice.

Background: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery. Methods: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo. The current analysis reports on the subgroup of patients from the trial with a history of coronary artery bypass grafting. Results: Of the 8179 patients randomized in REDUCE-IT, a total of 1837 (22.5%) had a history of coronary artery bypass grafting, with 897 patients randomized to icosapent ethyl and 940 to placebo. Baseline characteristics were similar between treatment groups. Randomization to icosapent ethyl was associated with a significant reduction in the primary end point (hazard ratio [HR], 0.76 [95% CI, 0.63–0.92]; P =0.004), in the key secondary end point (HR, 0.69 [95% CI, 0.56–0.87]; P =0.001), and in total (first plus subsequent or recurrent) ischemic events (rate ratio, 0.64 [95% CI, 0.50–0.81]; P =0.0002) compared with placebo. This yielded an absolute risk reduction of 6.2% (95% CI, 2.3%–10.2%) in first events, with a number needed to treat of 16 (95% CI, 10–44) during a median follow-up time of 4.8 years. Safety findings were similar to the overall study: beyond an increased rate of atrial fibrillation/flutter requiring hospitalization for at least 24 hours (5.0% vs 3.1%; P =0.03) and a nonsignificant increase in bleeding, occurrences of adverse events were comparable between groups. Conclusions: In REDUCE-IT patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl was associated with significant reductions in first and recurrent ischemic events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01492361.

BACKGROUND: Compared with everolimus-eluting metallic stents, the Absorb bioresorbable scaffold (BRS) results in increased rates of myocardial infarction (MI) and scaffold thrombosis (ST) during its three-year bioresorption phase. It is unknown whether prolonged dual antiplatelet therapy (DAPT) duration might decrease the risk of ischaemic events. AIMS: We sought to evaluate the impact of DAPT duration on ischaemic and bleeding outcomes following BRS implantation. METHODS: We conducted an individual patient data pooled analysis from four ABSORB randomised trials and one prospective ABSORB registry. Study endpoints were MI, ST, bleeding, and death up to three-year follow-up. Propensity score-adjusted Cox regression analysis was used to account for baseline differences related to DAPT duration. RESULTS: The five ABSORB studies included 2,973 patients. DAPT use was 91.7%, 53.2%, and 48.0% at 1, 2, and 3 years, respectively. DAPT use within the first year after BRS implantation was associated with markedly lower risks of MI (adjusted hazard ratio [aHR] 0.17, 95% CI: 0.10-0.32; p

Background The long-term prognostic impact of IVUS findings following Absorb BVS implantation remains uncertain. This study aimed to identify the IVUS predictors of long-term clinical outcomes following ABSORB bioresorbable vascular scaffold (BVS) implantation from the pooled IVUS substudy cohorts of the ABSORB III and Japan trials. Methods A total of 298 lesions in 286 patients were enrolled with 2:1 randomization to ABSORB BVS vs. cobalt-chromium everolimus-eluting stents. This sub-analysis included 168 lesions of 160 patients in the Absorb arm whose post-procedural quantitative IVUS were available. The primary endpoint of this analysis was device-oriented composite endpoint (DOCE) of target lesion failure, including cardiac death, target vessel-related myocardial infarction, or ischemia-driven target lesion revascularization. The median follow-up duration was 4.9 [3.1–5.0] years. Results During follow-up, DOCE occurred in 10.1% of lesions treated with Absorb BVS. Among several post-procedural IVUS indices associated with DOCE, non-uniform device expansion (defined as uniformity index = minimum / maximum device area) (hazard ratio 0.47 per 0.1 increase [95%CI 0.28 to 0.77]; p = 0.003) and residual reference plaque burden (hazard ratio 4.01 per 10% increase [95%CI 1.50 to 10.77]; p = 0.006) were identified as independent predictors of DOCE by Cox multivariable analysis. Conclusions Nonuniform device expansion and substantial untreated residual plaque in reference segments were associated with long-term adverse events following BVS implantation. Baseline imaging to identify the appropriate device landing zone and procedural imaging to achieve uniform device expansion if possible (e.g. through post-dilatation) may improve clinical outcomes of BVS implantation. Clinical trial registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT01751906 (ABSORB III); NCT01844284 (ABSORB Japan).

Background: Accelerated endothelial healing after targeted antiproliferative drug delivery may limit the long-term inflammatory response of drug-eluting stents (DESs). The novel Supreme DES is designed to synchronize early drug delivery within 4 to 6 weeks of implantation, leaving behind a prohealing permanent base layer. Whether the Supreme DES is safe and effective in the short term and can improve long-term clinical outcomes is not known. Methods: In an international, 2:1 randomized, single-blind trial, we compared treatment with Supreme DES to durable polymer everolimus-eluting stents (DP-EES) in patients with acute and chronic coronary syndromes. The primary end point was target lesion failure—a composite of cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization. The trial was designed to demonstrate noninferiority (margin of 3.58%) of the Supreme DES at 12 months compared with DP-EES (URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03168776). Results: From October 2017 to July 2019, a total of 1629 patients were randomly assigned (2:1) to the Supreme DES (N=1086) or DP-EES (N=543). At 12 months, target lesion failure occurred in 57 of 1057 patients (5.4%) in the Supreme DES group and in 27 of 532 patients (5.1%) in the DP-EES group (absolute risk difference, 0.32% [95% CI, −1.87 to 2.5]; P non inferiority =0.002]. There were no significant differences in rates of device success, clinically driven target lesion revascularization, or stent thrombosis at 12 months, and the safety composite of cardiovascular death and target vessel myocardial infarction was 3.5% versus 4.6% (hazard ratio, 0.76 [95% CI, 0.46–1.25]) with Supreme DES compared with DP-EES, although rates of combined clinically and non–clinically driven target lesion revascularization at 12 months were higher with Supreme DES. Conclusions: Among patients with acute and chronic coronary syndromes undergoing percutaneous coronary intervention, the Supreme DES proved to be noninferior to the standard DP-EES. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03168776.

A significant proportion of lesions treated with transcatheter interventions in the coronary and peripheral vascular beds exhibit moderate to severe calcific plaques known to portend lower procedural success rates, increased peri-procedural adverse events, and unfavorable clinical outcomes compared with noncalcific plaques. Adapted from lithotripsy technology used for treatment of ureterorenal calculi, intravascular lithotripsy (IVL) is a novel technique for the treatment of severely calcific plaque lesions that uses acoustic shockwaves in a balloon-based delivery system. Shockwaves induce calcium fractures, which facilitate stent expansion and luminal gain. In this review, the authors summarize the physics, preclinical and clinical data on IVL use in the coronary and peripheral vasculature, and future directions of IVL in transcatheter cardiovascular therapies.

Objectives The aim of this pooled analysis was to assess the cumulative safety and effectiveness of coronary intravascular lithotripsy (IVL). Background The clinical outcomes of IVL to opt...

Background The efficacy of thoracic endovascular aortic repair (TEVAR) of chronic type B aortic dissection (cTBAD) is controversial. Only limited evidence describes temporal anatomic changes after TEVAR for cTBAD and their relationship to outcomes. We sought to investigate early aortic remodeling events after TEVAR for cTBAD with thoracic aneurysm and determine the association with reintervention and survival. Methods Records from 95 cTBAD patients undergoing TEVAR from 2005 to 2017 were reviewed. Using 3-dimensional centerline analysis, anatomic phenotyping of the thoracoabdominal aorta was performed. Reverse aortic remodeling (RAR) was defined by a ≥5-mm reduction in maximal thoracic aortic diameter. Kaplan-Meier analysis estimated freedom from reintervention and survival. Results Visceral segment dissection involvement was present in 89% of patients (n = 85), and the mean preoperative thoracic diameter was 63 mm (SD, 10). Complete thoracic false lumen thrombosis occurred in 71% of patients (n = 67), whereas abdominal false lumen thrombosis was documented in 60% (n = 57) by 6 months. RAR occurred in 41%. Aortic reintervention rate was 39% (n = 37). The 1- and 3-year freedom from reintervention was significantly higher in subjects experiencing early RAR (log-rank P = .02), but reintervention did not impact overall survival (log-rank P = .9). Similarly, overall survival was similar between patients with or without RAR (log-rank P = .4). Conclusions Early RAR is associated with decreased rates of reintervention; however, overall survival is not impacted by these changes. TEVAR for cTBAD results in a high rate of reintervention, which mandates vigilant surveillance protocols.

Background Superior mesenteric artery aneurysms (SMAAs) are a rare clinical problem that can be associated with significant morbidity and mortality. The optimal surgical approach for both mycotic and degenerative SMAAs remains poorly defined. The study was designed to review our institutional experience and develop a treatment algorithm. Methods A single-institution, retrospective review was performed to document presentation, treatment, and outcomes of patients undergoing surgical repair of SMAAs from 2003 to 2020. The primary end-point was 30-day mortality, and secondary end-points included complications, patency, freedom from reinfection, freedom from reintervention, and survival. Results Eighteen patients (mean age: 46 ± 16 yrs; 50% male; mean diameter 2.4 ± 2.0 cm) underwent treatment of mycotic (50%) or degenerative (50%) SMAAs. Abdominal pain (66%) was the most common presenting symptom, and the diagnosis was confirmed with CT arteriography. Endocarditis secondary to intravenous drug abuse was responsible for most (88%) of the mycotic SMAAs, with a majority (66%) having positive cultures and Streptococcus being the most common organism. The majority (61%) of patients underwent urgent or emergent repair with aneurysmectomy and interposition saphenous vein bypass being the most common treatment of mycotic SMAAs while aneurysmectomy and prosthetic bypass were used most frequently for degenerative aneurysms. The operative mortality rate was 6% with a major complication rate of 17% (n = 3 patients: respiratory failure/reintubation-1, pulmonary embolism-1, necrotizing pancreatitis/graft disruption and death-1). The single death occurred in a patient with a degenerative aneurysm that developed postoperative pancreatitis and multiple organ dysfunction. The mean clinical follow-up time was 25 ± 48 (95% CI 1–48) months. The estimated primary patency, freedom from reinfection, and freedom from reintervention were 93 ± 7 %, 94 ± 5%, and 94 ± 5%, respectively, at 1 year. The overall mean survival was 55 ± 51 (95% CI 30–80) months with an estimated survival at 3 years of 77 ± 10%. Conclusions SMAAs associated with both degenerative and mycotic etiologies can be treated using a variety of surgical approaches with acceptable morbidity and mortality. Mycotic SMAAs should likely be repaired, regardless of size, while the indications for asymptomatic, degenerative aneurysms remain to be defined by further natural history studies.

Aims Cardiosphere-derived cells (CDCs) are cardiac progenitor cells that exhibit disease-modifying bioactivity in various models of cardiomyopathy and in previous clinical studies of acute myocardial infarction (MI), dilated cardiomyopathy, and Duchenne muscular dystrophy. The aim of the study was to assess the safety and efficacy of intracoronary administration of allogeneic CDCs in the multicentre, randomized, double-blinded, placebo-controlled, intracoronary ALLogeneic heart STem cells to Achieve myocardial Regeneration (ALLSTAR) trial. Methods and results We enrolled patients 4 weeks to 12 months after MI, with left ventricular ejection fraction (LVEF) ≤45% and LV scar size ≥15% of LV mass by magnetic resonance imaging (MRI). A pre-specified interim analysis was performed when 6-month MRI data were available. The trial was subsequently stopped due to the low probability of detecting a significant treatment effect of CDCs based on the primary endpoint. Patients were randomly allocated in a 2:1 ratio to receive CDCs or placebo in the infarct-related artery by stop-flow technique. The primary safety endpoint was the occurrence, during 1-month post-intracoronary infusion, of acute myocarditis attributable to allogeneic CDCs, ventricular tachycardia- or ventricular fibrillation-related death, sudden unexpected death, or a major adverse cardiac event (death or hospitalization for heart failure or non-fatal MI or need for left ventricular assist device or heart transplant). The primary efficacy endpoint was the relative percentage change in infarct size at 12 months post-infusion as assessed by contrast-enhanced cardiac MRI. We randomly allocated 142 eligible patients of whom 134 were treated (90 to the CDC group and 44 to the placebo group). The mean baseline LVEF was 40% and the mean scar size was 22% of LV mass. No primary safety endpoint events occurred. There was no difference in the percentage change from baseline in scar size (P = 0.51) between CDCs and placebo groups at 6 months. Compared with placebo, there were significant reductions in LV end-diastolic volume (P = 0.02), LV end-systolic volume (P = 0.02), and N-terminal pro b-type natriuretic peptide (NT-proBNP) (P = 0.02) at 6 months in CDC-treated patients. Conclusion Intracoronary infusion of allogeneic CDCs in patients with post-MI LV dysfunction was safe but did not reduce scar size relative to placebo at 6 months. Nevertheless, the reductions in LV volumes and NT-proBNP reveal disease-modifying bioactivity of CDCs. Trial registration Clinicaltrials.gov identifier: NCT01458405.

Prolonged use of dual antiplatelet therapy (DAPT) post-percutaneous coronary intervention (PCI) has been shown to reduce the risk of major adverse cardiovascular events (MACE), but with increased bleeding. It remains unknown whether biomarkers of platelet activation may be useful for identifying patients at increased risk of MACE. The DAPT study was a randomized trial of 12 versus 30 months of DAPT in patients who underwent PCI. Serum biomarkers [myeloid-related protein (MRP)-8/14, P-selectin, soluble CD-40 ligand (sCD40L)] were assessed in 1399 patients early post-PCI. On-treatment platelet reactivity index (PRI) using VASP phosphorylation was assessed in 443 patients randomized to continued DAPT at 1 year. MACE was defined as CV death, MI, or ischemic stroke. Multivariable models were adjusted for baseline characteristics, index event, and stent type. A stepwise increase in the risk of MACE was observed with increasing tertiles of both MRP-8/14 and P-selectin (p-trend = 0.04 for both). After multivariable adjustment, the adjusted HR (95% CI) for MACE in patients in the top tertile was 1.94 (1.14–3.30) for MRP-8/14 and 1.62 (0.99–2.64) for P-selectin. In contrast, baseline sCD40L was not associated with CV risk. Among patients randomized to continued DAPT, higher on-treatment platelet reactivity was not significantly associated with risk of MACE (p-trend = 0.32; adj-HR T3 vs. T1 1.54, 95% CI 0.20–12.18) or bleeding (P-trend = 0.17; adj-HR 0.25, 95% CI 0.05–1.21). MRP-8/14 and soluble P-selectin may be useful for identifying patients at increased risk of MACE after PCI. The utility of on-treatment platelet function testing requires further study. Clinical Trial Registration https://www.clinicaltrials.gov . Unique identifier NCT00977938.

Intravascular lithotripsy (IVL) may be useful to deliver Impella devices in patients with peripheral arterial disease. Twelve patients were treated with peripheral IVL prior to Impella insertion. A total of 100% of patients underwent successful device implantation with no IVL complications. IVL can facilitate transfemoral access for Impella insertion. (Level of Difficulty: Advanced.), Graphical abstract, Intravascular lithotripsy (IVL) may be useful to deliver Impella devices in patients with peripheral arterial disease. Twelve patients were treated…

Background Integrin α7β1 is a major laminin receptor in skeletal and cardiac muscle. In skeletal muscle, integrin α7β1 plays an important role during muscle development and has been described as an important modifier of skeletal muscle diseases. The integrin α7β1 is also highly expressed in the heart, but its precise role in cardiac function is unknown. Mutations in the integrin α7 gene ( ITGA7 ) have been reported in children with congenital myopathy. Methods and Results In this study, we described skeletal and cardiac muscle pathology in Itga7 −/− mice and 5 patients from 2 unrelated families with ITGA7 mutations. Proband in family 1 presented a homozygous c.806_818del [p.S269fs] variant, and proband in family 2 was identified with 2 intron variants in the ITGA7 gene. The complete absence of the integrin α7 protein in muscle supports the ITGA7 mutations are pathogenic. We performed electrocardiography, echocardiography, or cardiac magnetic resonance imaging, and histological biopsy analyses in patients with ITGA7 deficiency and Itga7 −/− mice. The patients exhibited cardiac dysrhythmia and dysfunction from the third decade of life and late‐onset respiratory insufficiency, but with relatively mild limb muscle involvement. Mice demonstrated corresponding abnormalities in cardiac conduction and contraction as well as diaphragm muscle fibrosis. Conclusions Our data suggest that loss of integrin α7 causes a novel form of adult‐onset cardiac dysfunction indicating a critical role for the integrin α7β1 in normal cardiac function and highlights the need for long‐term cardiac monitoring in patients with ITGA7 ‐related congenital myopathy.

Background: The Absorb everolimus-eluting bioresorbable vascular scaffold (BVS) provides early drug delivery and mechanical support similar to those of metallic drug-eluting stents, followed by complete resorption in ≈3 years with recovery of vascular structure and function. The ABSORB III trial demonstrated noninferior rates of target lesion failure (cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization) at 1 year with BVS compared with cobalt chromium everolimus-eluting stents. Between 1 and 3 years and cumulative to 3 years, adverse event rates (particularly target vessel myocardial infarction and scaffold thrombosis) were increased after BVS. We sought to assess clinical outcomes after BVS through 5 years, including beyond the 3-year time point of complete scaffold resorption. Methods: Clinical outcomes from ABSORB III were analyzed by randomized device (intention to treat) cumulative to 5 years and between 3 and 5 years. Results: Rates of target lesion failure, target vessel myocardial infarction, and scaffold thrombosis were increased through the 5-year follow-up with BVS compared with everolimus-eluting stents. However, between 3 and 5 years, reductions in the relative hazards of the BVS compared with everolimus-eluting stents were observed, particularly for target lesion failure (hazard ratio, 0.83 [95% CI, 0.55–1.24] versus 1.35 [95% CI, 1.02–1.78]; P int =0.052) and scaffold thrombosis (hazard ratio, 0.26 [95% CI, 0.02–2.87] versus 3.23 [95% CI, 1.25–8.30]; P int =0.056) compared with the 0- to 3-year time period. Conclusions: In the ABSORB III trial, cumulative 5-year adverse event rates were increased after BVS compared with everolimus-eluting stents. However, the period of excess risk for BVS ended at 3 years, coincident with complete scaffold resorption. Clinical Trial Registration: URL: https://clinicaltrials.gov . Unique identifier: NCT01751906.

Guidelines recommend individualization of dual antiplatelet therapy (DAPT) duration. Whether to guide decisions based on bleeding risk, ischemic risk or a combination is not known.To compare a bleeding prediction model, an ischemic prediction model, and the DAPT score in guiding DAPT duration.11,648 patients in the DAPT Study were categorized into higher and lower risk using a bleeding model, an ischemic model, and the DAPT score. Effect of 30 vs. 12 months of DAPT on bleeding events, ischemic events, and the combination (net-adverse clinical events [NACE]) was assessed.Among patients stratified with the bleeding model, 30 vs. 12 months of DAPT resulted in similar ischemic and bleeding event rates. With the ischemic model, however, higher risk patients had a greater reduction in ischemic events with extended duration of DAPT (difference in risk differences [DRD]: -2.6%, 95% CI: -3.9 to -1.3%; p 0.01), and a smaller increase in bleeding (DRD: -1.0%, 95% CI: -2.1-0.0%; p = 0.04). Similarly, high DAPT score patients had a greater reduction in ischemic events with extended DAPT duration (DRD: -2.4%, 95%: CI: -3.6 to -1.1%; p 0.01) and a smaller increase in bleeding (DRD: -1.2%, 95%: CI: -2.2-0.0%; p = 0.02). Although NACE was similar for bleeding risk groups, NACE was significantly reduced with extended DAPT in the higher ischemic risk and high DAPT score groups.In this low-bleeding risk population, stratifying patients based on predicted ischemic risk and the DAPT score best discerned benefit versus harm of extended DAPT duration on ischemic events, bleeding events, and NACE.Duration of dual antiplatelet therapy (DAPT) should be guided by an individualized risk assessment. Bleeding risk tools have emerged to identify patients at high bleeding risk for whom truncated DAPT therapy may be safest. In a lower bleeding risk population, however, whether DAPT duration should be guided by bleeding risk, ischemic risk, or a combination is unknown. In this analysis, implementation of a score based on ischemic risk prediction and the DAPT score (a combination of ischemic and bleeding risk) best predicted ischemic events, bleeding events, and net-adverse clinical events (NACE).

Graphical Abstract Graphical AbstractThe direct and indirect impact of COVID-19 on cardiovascular disease.

Background\ud Intravascular lithotripsy (IVL) can be used to assist stent deployment in severe coronary artery calcifications (CAC).\ud \ud Methods\ud Studies employing IVL for CAC lesions were included. The primary outcomes included clinical and angiographic success. The secondary outcomes, including lumen gain, maximum calcium thickness, and calcium angle at the final angiography site, minimal lumen area site, and minimal stent area site, were analyzed by the random-effects model to calculate the pooled standardized mean difference. Tertiary outcomes included safety event ratios.\ud \ud Results\ud Seven studies (760 patients) were included. The primary outcomes: pooled clinical and angiographic success event ratio parentage of IVL was 94.4% and 94.8%, respectively. On a random effect model for standard inverse variance for secondary outcomes showed: minimal lumen diameter increase with IVL was 4.68 mm (p-value < 0.0001, 95% CI 1.69–5.32); diameter decrease in the stenotic area after IVL session was −5.23 mm (95 CI –22.6–12.8). At the minimal lumen area (MLA) and final minimal stent area (MSA) sites, mean lumen area gain was 1.42 mm2 (95% CI 1.06–1.63; p < 0.00001) and 1.34 mm2 (95% CI 0.71–1.43; p < 0.00001), respectively. IVL reduced calcium thickness at the MLA site (SMD −0.22; 95% CI −0.40–0.04; P = 0.02); calcium angle was not affected at the MLA site. The tertiary outcomes: most common complication was major adverse cardiovascular events (n = 48/669), and least common complication was abrupt closure of the vessel (n = 1/669).\ud \ud Conclusions\ud Evidence suggests that IVL safely and effectively facilitates stent deployment with high angiographic and clinical success rates in treating severely calcified coronary lesions.

Unplanned repeat coronary angiography (CAG) after balloon angioplasty for ST-elevation myocardial infarction (STEMI) was common before the advent of coronary stenting. Limited data are available regarding the role of unplanned repeat CAG in contemporary percutaneous coronary intervention (PCI) for STEMI. Therefore, we analyzed a large, 2-center prospective STEMI registry (January 2011 to June 2020) stratified by the presence or absence of unplanned repeat CAG during index hospitalization. Patients with planned CAG for staged PCI or experimental drug administration were excluded. Among 3,637 patients with STEMI, 130 underwent unplanned repeat CAG (3.6%) during index hospitalization. These patients were more likely to have cardiogenic shock (16% vs 9.8%, p = 0.021), left anterior descending culprit (44% vs 31%, p0.001), lower left ventricular ejection fraction (45% vs 52%, p0.001), and higher peak troponin levels (22 vs 8 ng/ml, p0.001) than those without repeat CAG. At repeat CAG, 80 patients had a patent stent (62%) including 65 requiring no further intervention (50%) and 15 who underwent intervention on a nonculprit lesion (12%). Only 32 patients had stent thrombosis (25%). Repeat CAG was associated with a higher incidence of recurrent MI (19% vs 0%, p0.001) and major bleeding (12% vs 4.5%, p0.001), yet similar in-hospital mortality (7% vs 6.4%, p = 0.93) than those without repeat CAG. In conclusion, in the era of contemporary PCI for STEMI, unplanned repeat CAG during index hospitalization was infrequent and more commonly observed in patients with left anterior descending culprit in the presence of significant left ventricular dysfunction or shock and was associated with higher in-hospital recurrent myocardial infarction and major bleeding complications.

BackgroundMost cell therapy trials failed to show an improvement in global left ventricular (LV) function measures after myocardial infarction (MI). Myocardial segments are heterogeneously impacted by MI. Global LV function indices are not able to detect the small treatment effects on segmental myocardial function which may have prognostic implications for cardiac events. We aimed to test the efficacy of allogeneic cardiosphere-derived cells (CDCs) for improving regional myocardial function and contractility.MethodsIn this exploratory analysis of a randomised clinical trial, 142 patients with post-MI with LVEF ResultsIn total, 124 patients completed the 6-month follow-up (mean (SD) age 54.3 (10.8) and 108 (87.1%) men). Segmental Ecc improvement was significantly greater in patients receiving CDC (−0.5% (4.0)) compared with placebo (0.2% (3.7), p=0.05). The greatest benefit for improvement in segmental Ecc was observed in segments containing scar tissue (change in segmental Ecc of −0.7% (3.5) in patients receiving CDC vs 0.04% (3.7) in the placebo group, p=0.04).ConclusionsIn patients with post-MI LV dysfunction, CDC administration resulted in improved segmental myocardial function. Our findings highlight the importance of segmental myocardial function indices as an endpoint in future clinical trials of patients with post-MI.Trial registration numberNCT01458405.

Objectives To investigate the long-term vasomotor response and inflammatory changes in Absorb bioresorbable vascular scaffold (BVS) and metallic drug-eluting stent (DES) implanted artery. Background Clinical evidence has demonstrated that compared to DES, BVS is associated with higher rates of target lesion failure. However, it is not known whether the higher event rates observed with BVS are related to endothelial dysfunction or inflammation associated with polymer degradation. Methods Ten Absorb BVS and six Xience V DES were randomly implanted in the main coronaries of six nonatherosclerotic swine. At 4-years, vasomotor response was evaluated in vivo by quantitative coronary angiography response to intracoronary infusion of Ach and ex vivo by the biomechanical response to prostaglandin F2-α (PGF2-α), substance P and bradykinin and gene expression analysis. Results Absorb BVS implanted arteries showed significantly restored vasoconstrictive responses after Ach compared to in-stent Xience V. The contractility of Absorb BVS treated segments induced by PGF2-α was significantly greater compared to Xience V treated segments and endothelial-dependent vasorelaxation was greater with Absorb BVS compared to Xience V. Gene expression analyses indicated the pro-inflammatory lymphotoxin-beta receptor (LTβR) signaling pathway was significantly upregulated in arteries treated with a metallic stent compared to Absorb BVS treated arterial segments. Conclusions At 4 years, arteries treated with Absorb BVS compared with Xience V, demonstrate significantly greater restoration of vasomotor responses. Genetic analysis suggests mechanobiologic reparation of Absorb BVS treated arteries at 4 years as opposed to Xience V treated vessels.

Acute DeBakey I or II aortic dissection (AD) is a surgical emergency with significant mortality if not repaired immediately. We present the case of a 49-year-old man with acute type I AD, who initially underwent zone 2 arch replacement for a primary arch tear. A calcified ductus arteriosus was noted during arch reconstruction. He exhibited exsanguinating hemorrhage from the proximal descending thoracic aorta upon an initial attempt to wean off cardiopulmonary bypass. Hemostasis was achieved with retrograde transfemoral thoracic endovascular aortic repair and transmediastinal external cinch around the descending aorta to obliterate false lumen flow.

Background Coronary stenting without angioplasty pretreatment (direct stenting) may simplify procedures in appropriate lesions. Direct stenting is facilitated by smaller profile coronary stent platforms. The present study was designed for regulatory approval of a novel drug-eluting coronary stent and incorporates both randomized comparison for non-inferiority to an approved predicate device as well as a nested evaluation of subjects eligible for direct stenting. Study Design and Objectives. Prospective, single-blind, randomized, active-control, multi-center study designed to assess the safety and efficacy of the novel Svelte sirolimus-eluting stent (SES) systems. A total of 1630 subjects with up to 3 target lesions will be randomized 1:1 to the Svelte SES versus either the Xience or Promus everolimus-eluting stents (control). Randomization will be stratified by whether or not a direct stenting strategy is planned by the investigator. The primary endpoint is target lesion failure (TLF) at 12 months post index procedure, defined as cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization, and the primary analysis is a non-inferiority test with a non-inferiority margin of 3.58%. Secondary clinical endpoints include individual components of TLF, stent thrombosis and measures of procedural resource utilization including contrast administration, fluoroscopy exposure and procedural resource utilization as well as costs. Conclusion The OPTMIZE Trial will evaluate the safety, efficacy and clinical value of the novel Svelte SES in subjects with up to 3 lesions, and will provide a comparison of direct stenting between randomized devices.

ObjectivesCalcific aortic valve disease (CAVD) is a progressive disease ranging from aortic valve (AoV) sclerosis to AoV stenosis (AS), characterised by severe calcification with impaired leaflet function. Due to the lack of early symptoms, the pathological progression towards valve dysfunction is poorly understood. The early patterns of AoV calcification and altered extracellular matrix (ECM) organisation were analysed in individuals postmortem without clinical AS compared with clinical AS.MethodsHistological patterns of calcification and ECM organisation in postmortem AoV leaflets without clinical AS obtained from a tissue repository and surgical specimens obtained from individuals with clinical AS were compared with in vivo imaging prior to transcatheter AoV implantation.ResultsAoV calcification was detected in all samples from individuals >50 years old, with severity increasing with age, independent of known CAVD risk factors. Two distinct types of calcification were identified: ‘Intrinsic’, primarily found at the leaflet hinge of postmortem leaflets, accompanied by abnormal collagen and proteoglycan deposition; and ‘Nodular’, extending from the middle to the tip regions in more severely affected postmortem leaflets and surgical specimens, associated with increased elastin fragmentation and loss of elastin integrity. Even in the absence of increased thickening, abnormalities in ECM composition were observed in postmortem leaflets without clinical AS and worsen in clinical AS.ConclusionsTwo distinct phenotypes of AoV calcification are apparent. While the ‘nodular’ form is recognised on in vivo imaging and is present with CAVD and valve dysfunction, it is unclear if the ‘intrinsic’ form is pathological or detected on in vivo imaging.

Thoracic endovascular aortic repair (TEVAR) has become a mainstay of therapy for acute and chronic type B aortic dissection (TBAD). Dynamic aortic morphologic changes, untreated dissected aorta, and persistent false lumen perfusion have significant consequences for reintervention after TEVAR for TBAD. However, few reports contrast differences in secondary aortic intervention (SAI) after TEVAR for TBAD or describe their influence on mortality. This analysis examined incidence, timing, and types of SAI after TEVAR for acute and chronic TBAD and determined their impact on survival.All TEVAR procedures for acute and chronic TBAD (2005-2016) were retrospectively reviewed. Patients with staged (30 days) or concomitant ascending aortic arch repair or replacement were excluded. Acuity was defined by symptom onset (0-30 days, acute;30 days, chronic). SAI procedures were grouped into open (intended treatment zone or remote aortic site), major endovascular (TEVAR extension or endograft implanted at noncontiguous site), and minor endovascular (side branch or false lumen embolization) categories. Kaplan-Meier methodology was used to estimate freedom from SAI and survival. Cox proportional hazards were used to identify SAI predictors.TEVAR for TBAD was performed in 258 patients (acute, 49% [n = 128]; chronic, 51% [n = 130]). Mean follow-up was 17 ± 22 months with an overall SAI rate of 27% (n = 70; acute, 22% [28]; chronic, 32% [42]; odds ratio, 1.7; 95% confidence interval, 0.9-2.9; P = .07]. Median time to SAI was significantly less after acute than after chronic dissection (0.7 [0-12] vs 7 [0-91] months; P .001); however, freedom from SAI was not different (1-year: acute, 67% ± 4%, vs chronic, 68% ± 5%; 3-year: acute, 65% ± 7%, vs chronic, 52% ± 8%; P = .7). Types of SAI were similar (acute vs chronic: open, 61% vs 55% [P = .6]; major endovascular, 36% vs 38% [P = .8]; minor endovascular, 21% vs 21% [P = 1]). The open conversion rate (either partial or total endograft explantation: acute, 10% [13/128]; chronic, 15% [20/130]; P = .2) and incidence of retrograde dissection (acute, 6% [7/128]; chronic, 4% [5/130]; P = .5) were similar. There was no difference in survival for SAI patients (5-year: acute + SAI, 55% ± 9%, vs acute without SAI, 67% ± 8% [P = .3]; 5-year: chronic + SAI, 72% ± 6%, vs chronic without SAI, 72% ± 7% [P = .7]). Factors associated with SAI included younger age, acute dissection with larger maximal aortic diameter at presentation, Marfan syndrome, and use of arch vessel adjunctive procedures with the index TEVAR. Indication for the index TEVAR (aneurysm, malperfusion, rupture, and pain or hypertension) or remote preoperative history of proximal arch procedure was not predictive of SAI.SAI after TEVAR for TBAD is common. Acute TBAD has a higher proportion of early SAI; however, chronic TBAD appears to have ongoing risk of remediation after the first postoperative year. SAI types are similar between groups, and the occurrence of aorta-related reintervention does not affect survival. Patients' features and anatomy predict need for SAI. These data should be taken into consideration for selection of patients, device design, and surveillance strategies after TEVAR for TBAD.

Conduction abnormalities after transcatheter aortic valve replacement (TAVR) account for a high percentage of post-TAVR complications. Areas covered: The etiology of conduction abnormalities is closely tied to cardiac anatomy (length of membranous septum, degree of calcification, location of left bundle within the membranous septum), baseline conduction abnormalities (preprocedure right bundle branch block), and procedural variables (type of valve, depth of implant). Management of new high-grade AV block and new left bundle branch block varies by institution in the absence of consensus guidelines. Expert opinion: Authors describe the incidence, etiology, outcomes, and management of conduction abnormalities related to aortic stenosis and TAVR.

Introduction Aortic stenosis (AS) imposes a significant afterload on the left ventricle, but regional manifestations of the overall load may not be uniform, leading to mechanical dyssynchrony. Accordingly, we evaluated the prevalence of dyssynchrony in patients with severe AS at baseline as well as changes after transfemoral aortic valve replacement (TAVR). Methods This study is a retrospective analysis of 225 patients in sinus rhythm who underwent TAVR for severe AS, in whom inter-ventricular and intra-ventricular dyssynchrony were measured at baseline, discharge, 1 month, and 1 year. Inter-ventricular dyssynchrony was defined as the difference between left and right ventricular pre-ejection intervals; intra-ventricular dyssynchrony was defined as the difference between time to peak systolic velocity of the basal septal and lateral segments. Patients were further stratified into those with QRS 120 ms. Results At baseline, a quarter of patients met the criterion for significant inter-ventricular dyssynchrony, and a third had evidence of intra-ventricular dyssynchrony. Both decreased after TAVR although only the intra-ventricular dyssynchrony reached statistical significance. The interplay between QRS duration and changes in inter- and intra-ventricular dyssynchrony are also explored. Conclusions In patients with severe AS, there was evidence of mechanical dyssynchrony that is improved post-TAVR. Whether dyssynchrony is clinically and prognostically significant, and if it represents a potential target for additional therapy remains to be studied.

Critical limb ischemia (CLI) is the most severe manifestation of peripheral artery disease (PAD) and is characterized by high rates of morbidity and mortality. As with most severe cardiovascular disease manifestations, Black individuals disproportionately present with CLI. Accordingly, there remains a clear need to better understand the reasons for this discrepancy and to facilitate personalized therapeutic options specific for this population. Gastrocnemius muscle was obtained from White and Black healthy adult volunteers and patients with CLI for whole transcriptome shotgun sequencing (WTSS) and enrichment analysis was performed to identify alterations in specific Reactome pathways. When compared to their race-matched healthy controls, both White and Black patients with CLI demonstrated similar reductions in nuclear and mitochondrial encoded genes and mitochondrial oxygen consumption across multiple substrates, indicating a common bioenergetic paradigm associated with amputation outcomes regardless of race. Direct comparisons between tissues of White and Black patients with CLI revealed hemostasis, extracellular matrix organization, platelet regulation, and vascular wall interactions to be uniquely altered in limb muscles of Black individuals. Among traditional vascular growth factor signaling targets, WTSS revealed only Tie1 to be significantly altered from White levels in Black limb muscle tissues. Quantitative reverse transcription polymerase chain reaction validation of select identified targets verified WTSS directional changes and supports reductions in MMP9 and increases in NUDT4P1 and GRIK2 as unique to limb muscles of Black patients with CLI. This represents a critical first step in better understanding the transcriptional program similarities and differences between Black and White patients in the setting of amputations related to CLI and provides a promising start for therapeutic development in this population.

Background The dual antiplatelet therapy (DAPT) score, one of the first prediction tools to attempt to uncouple bleeding and ischemic risk following percutaneous coronary intervention, can help guide antiplatelet duration after coronary intervention. Evaluating the generalizability of the score is important to understand its utility in clinical practice. Methods We conducted a systematic review and meta-analysis of studies that validated the DAPT score. A random effect meta-analysis was performed of ischemic and bleeding risk based on DAPT score. A secondary analysis assessed the risk of longer versus shorter P2Y12 inhibitor duration on ischemic and bleeding risk in randomized controlled trials of DAPT duration. Results We identified 10 patient cohorts involving 88,563 patients. Compared with a low DAPT score, a high DAPT score was associated with increased ischemic risk (RR: 1.62, 95% CI: 1.41-1.87) and reduced bleeding risk (RR: 0.80, 95% CI: 0.70-0.92). In three randomized trials of DAPT duration that contained information on the DAPT score, the relative risk of net adverse clinical events (combined ischemic and bleeding events) with longer duration of DAPT was 1.56 (95% CI: 0.77-3.19) for low DAPT score patients, and 0.86 (95% CI: 0.61-1.21) for high DAPT score patients (pinteraction = .14). Conclusions In this large meta-analysis, the DAPT score consistently stratified bleeding and ischemic risk in opposing directions across several different study populations. More evaluation is needed to understand if the effect of longer DAPT duration on NACE is modified by the DAPT score in current practice.

Background: Prolonged dual antiplatelet therapy (DAPT) after percutaneous coronary intervention is associated with increased bleeding, despite a reduced incidence of ischemic events. The SYNERGY everolimus-eluting stent is a thin-strut platinum-chromium stent that elutes everolimus from a thin abluminal layer of bioabsorbable polymer. These design elements may facilitate rapid endothelialization and enable shorter-duration DAPT. Methods: EVOLVE Short DAPT prospectively evaluated the safety of 3-month DAPT in high bleeding risk patients treated with the SYNERGY everolimus-eluting stent, enrolling 2009 patients at 110 global sites. Patients with acute myocardial infarction or complex lesions were excluded. After percutaneous coronary intervention, patients were required to take DAPT (aspirin+P2Y 12 inhibitor) for 3 months, except those on chronic anticoagulation in whom aspirin was optional. Patients free of events (stroke, myocardial infarction, revascularization, and stent thrombosis) who discontinued P2Y 12 inhibitor at 3 months, but continued aspirin, and had at least 1 year of follow-up or an end point event were included in the primary analysis. Two powered coprimary end points were (1) death/myocardial infarction compared with a historical control and (2) study stent-related definite/probable stent thrombosis compared to a performance goal. Results: The analysis population consisted of 1487 patients. The adjusted rate of death/myocardial infarction between 3 and 15 months was 5.6% among patients receiving 3-month DAPT versus 5.7% patients in the 12-month DAPT control (propensity adjusted difference=−0.12%; 97.5% upper bound=1.63% which was less than the prespecified margin of 2.52; P non-inferiority =0.0016). The rate of study stent-related stent thrombosis between 3-15 months was 0.2% in the 3-month DAPT group (97.5% upper bound=0.63%; P =0.0005 for comparison to 1% performance goal). Conclusions: Favorable rates of ischemic outcomes were observed among selected high bleeding risk patients undergoing percutaneous coronary intervention with the SYNERGY everolimus-eluting stent who tolerated 3 months of P2Y 12 inhibitor and then discontinued it, supporting the safety of abbreviated DAPT with this stent platform. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02605447.