Long-Term Follow-Up of a High Risk Cohort After Stent Implantation in Saphenous Vein Grafts

AbstractObjectives. We sought to provide short- and long-term clinical outcomes of a high risk cohort treated with stents in saphenous vein grafts (SVGs).Background. Data on the long-term outcome of SVG stenting in high risk patients are limited.Methods. Johnson & Johnson stents were implanted in the SVGs of 186 patients (302 stents, 244 lesions). Ninety percent of patients presented with myocardial infarction (MI) or unstable angina (mean ±SD ejection fraction [EF] 44 ± 11%, patient age 71 ± 9 years, graft age 9.4 ± 5 years). Using a risk score classification, 155 patients (83%) were defined as high risk for repeat surgical repair or angioplasty.Results. The procedural success rate was 97.3%, with 2.7% major complications (death, Q wave MI, coronary artery bypass graft surgery [CABG]). Clinical follow-up was obtained in 177 patients (mean 19.1 ± 13.5 months, range 7 to 59). Event rates were 10% for death; 9% for MI; 11% for repeat CABG; and 15% for repeat angioplasty (total events 45%). Kaplan-Meier estimated survival and event-free survival at 4 years were 0.79 ± 0.06 and 0.29 ± 0.07, respectively. Predictors of death were congestive heart failure (p < 0.01) and EF <44% (p < 0.05). Predictors of combined events of death, MI and CABG were low EF (p < 0.01) and high SVG age (>10 years, p < 0.01). There were 66 revascularization procedures (35% of patients), 24% of which were in nontarget lesions. Fifty-three percent of the cardiac events occurred during the first year of follow-up. Of the 160 survivors, 36% were free of angina, 49% were in Canadian Cardiovascular Society functional class I or II, and 15% were in class III or IV. Sixty-nine percent of patients were in class I or II according to the Specific Activity Scale, and 31% of patients were in class III or IV.Conclusions. Balloon-expandable stent implantation in the SVGs of high risk patients is associated with a low early complication rate. Expected survival rates are good, as are the anginal and functional classifications, but there is a high rate of recurrent events and need for repeat revascularization. Vein graft stenting is an acceptable palliative option in many high risk patients

Leaflet thrombosis in transcatheter aortic valve intervention: mechanisms, prevention, and treatment options

IntroductionTranscatheter aortic valve intervention (TAVR) has emerged as a promising alternative to surgical aortic valve replacement for patients with severe aortic stenosis. However, leaflet thrombosis has raised concerns about the long-term durability and outcomes of TAVR. This study aims to provide an overview of the mechanisms, prevention strategies, and treatment options for leaflet thrombosis in TAVR.Clinical evidenceLeaflet thrombosis refers to the formation of blood clots on bioprosthetic valve leaflets, leading to impaired leaflet mobility, early valve degeneration and dysfunction, and potential clinical implications. While the mechanisms underlying thrombus formation on valve leaflets are not fully understood, several factors, such as altered blood flow patterns within valve neosinuses, prothrombotic surfaces, and patient-related causes, have been implicated. Two distinct entities have been identified, namely, hypoattenuated leaflet thickening and restricted leaflet motion. Their occurrence appears dynamic over time and is related to the valve type. Imaging, including transesophageal echocardiography and multidetector computed tomography, plays a crucial role in the diagnosis and follow-up of leaflet thrombosis.Prevention and treatment optionsPreventing leaflet thrombosis requires a comprehensive and tailored approach involving identifying high-risk patients, close monitoring, and antithrombotic therapy. Antithrombotic therapy with dual antiplatelet agents or anticoagulation is commonly employed in TAVR patients, although the optimal regimen is yet to be defined. Novel antithrombotic agents, such as direct oral anticoagulants, are being investigated for their efficacy and safety in preventing leaflet thrombosis. When leaflet thrombosis is detected, treatment options include intensified antithrombotic therapy, valve-in-valve intervention, or balloon valvuloplasty. The long-term outcomes and impact of leaflet thrombosis on valve durability and patient prognosis are areas of ongoing research.SummaryLeaflet thrombosis in TAVR is a considerable complication affecting valve function and patient outcomes. Understanding the mechanisms underlying thrombus formation and implementing appropriate prevention strategies are essential for mitigating this risk. Treatment options aim to restore leaflet mobility and optimize valve performance. Further research is needed to establish standardized protocols for antithrombotic therapy, identify high-risk patient populations, and determine the long-term consequences of leaflet thrombosis on TAVR outcomes

Transcatheter and Doppler waveform correlation in transcatheter aortic valve replacement

Transcatheter aortic valve replacement (TAVR) has become the preferred therapy for treatment of severe aortic stenosis in patients at intermediate to high risk of perioperative mortality following surgical aortic valve replacement. Haemodynamic assessment is an integral part of the procedure, and it is crucial for the operator to have an in-depth understanding of the haemodynamic alterations that occur during balloon aortic valvuloplasty and transcatheter valve deployment. Comprehension of the haemodynamic tracings is also pivotal for early recognition of periprocedural complications. With expanding indications for TAVR, it is imperative for members of the structural heart team to have an in-depth, nuanced understanding of transcatheter haemodynamic waveforms and their correlation with echocardiographic Doppler waveforms that are obtained periprocedurally during TAVR. This review provides a collection of transcatheter haemodynamic tracings and their corresponding Doppler echocardiography correlates that are demonstrative of physiological alterations and pathological lesions (complications) that occur during TAVR

Validation of the Cardiosphere Method to Culture Cardiac Progenitor Cells from Myocardial Tissue

At least four laboratories have shown that endogenous cardiac progenitor cells (CPCs) can be grown directly from adult heart tissue in primary culture, as cardiospheres or their progeny (cardiosphere-derived cells, CDCs). Indeed, CDCs are already being tested in a clinical trial for cardiac regeneration. Nevertheless, the validity of the cardiosphere strategy to generate CPCs has been called into question by reports based on variant methods. In those reports, cardiospheres are argued to be cardiomyogenic only because of retained cardiomyocytes, and stem cell activity has been proposed to reflect hematological contamination. We use a variety of approaches (including genetic lineage tracing) to show that neither artifact is applicable to cardiospheres and CDCs grown using established methods, and we further document the stem cell characteristics (namely, clonogenicity and multilineage potential) of CDCs.CPCs were expanded from human endomyocardial biopsies (n = 160), adult bi-transgenic MerCreMer-Z/EG mice (n = 6), adult C57BL/6 mice (n = 18), adult GFP(+) C57BL/6 transgenic mice (n = 3), Yucatan mini pigs (n = 67), adult SCID beige mice (n = 8), and adult Wistar-Kyoto rats (n = 80). Cellular yield was enhanced by collagenase digestion and process standardization; yield was reduced in altered media and in specific animal strains. Heparinization/retrograde organ perfusion did not alter the ability to generate outgrowth from myocardial sample. The initial outgrowth from myocardial samples was enriched for sub-populations of CPCs (c-Kit(+)), endothelial cells (CD31(+), CD34(+)), and mesenchymal cells (CD90(+)). Lineage tracing using MerCreMer-Z/EG transgenic mice revealed that the presence of cardiomyocytes in the cellular outgrowth is not required for the generation of CPCs. Rat CDCs are shown to be clonogenic, and cloned CDCs exhibit spontaneous multineage potential.This study demonstrates that direct culture and expansion of CPCs from myocardial tissue is simple, straightforward, and reproducible when appropriate techniques are used

Sex Differences in Outcomes After Percutaneous Coronary Intervention or Coronary Artery Bypass Graft for Left Main Disease: From the DELTA Registries

Background Controversy exists over whether sex has significant interaction with revascularization strategy for unprotected left main coronary artery disease. Higher mortality has been reported among women treated with percutaneous coronary intervention compared with coronary artery bypass grafting. Methods and Results The DELTA (Drug-Eluting Stents for Left Main Coronary Artery Disease) and DELTA-2 registries are international, multicentric registries evaluating the outcomes of subjects undergoing coronary revascularization for unprotected left main coronary artery disease. The primary outcome was a composite of death, myocardial infarction, or cerebrovascular accidents. The population consisted of 6253 patients, including 1689 (27%) women. Women were older and more likely to have diabetes and chronic kidney disease than men (P<0.05). At a median follow-up of 29 months (interquartile range 12-49), a significant interaction between sex and revascularization strategy was observed for the primary end point (pint=0.012) and all-cause death (pint=0.037). Among women, compared with percutaneous coronary intervention, coronary artery bypass grafting was associated with lower risk of the primary end point (event rate 9.5% versus 15.3%; adjusted hazard ratio [AHR], 0.53; 95% CI, 0.35-0.79, P<0.001) and all-cause death (event rate 5.6% versus 11.7% AHR, 0.50; 95% CI, 0.30-0.82) and no significant differences were observed in men. Conclusions In women undergoing coronary revascularization for unprotected left main coronary artery disease, coronary artery bypass grafting was associated with lower risk of death, myocardial infarction, or cerebrovascular accidents whereas no significant differences between coronary artery bypass grafting and percutaneous coronary intervention were observed in men. Further dedicated studies are needed to determine the optimal revascularization strategy in women with unprotected left main coronary artery disease. Keywords: cardiovascular disease in women; coronary revascularization; unprotected left main coronary artery disease

Two-year outcomes after transcatheter or surgical aortic-valve replacement.

BACKGROUND: The Placement of Aortic Transcatheter Valves (PARTNER) trial showed that among high-risk patients with aortic stenosis, the 1-year survival rates are similar with transcatheter aortic-valve replacement (TAVR) and surgical replacement. However, longer-term follow-up is necessary to determine whether TAVR has prolonged benefits. METHODS: At 25 centers, we randomly assigned 699 high-risk patients with severe aortic stenosis to undergo either surgical aortic-valve replacement or TAVR. All patients were followed for at least 2 years, with assessment of clinical outcomes and echocardiographic evaluation. RESULTS: The rates of death from any cause were similar in the TAVR and surgery groups (hazard ratio with TAVR, 0.90; 95% confidence interval [CI], 0.71 to 1.15; P=0.41) and at 2 years (Kaplan-Meier analysis) were 33.9% in the TAVR group and 35.0% in the surgery group (P=0.78). The frequency of all strokes during follow-up did not differ significantly between the two groups (hazard ratio, 1.22; 95% CI, 0.67 to 2.23; P=0.52). At 30 days, strokes were more frequent with TAVR than with surgical replacement (4.6% vs. 2.4%, P=0.12); subsequently, there were 8 additional strokes in the TAVR group and 12 in the surgery group. Improvement in valve areas was similar with TAVR and surgical replacement and was maintained for 2 years. Paravalvular regurgitation was more frequent after TAVR (P<0.001), and even mild paravalvular regurgitation was associated with increased late mortality (P<0.001). CONCLUSIONS: A 2-year follow-up of patients in the PARTNER trial supports TAVR as an alternative to surgery in high-risk patients. The two treatments were similar with respect to mortality, reduction in symptoms, and improved valve hemodynamics, but paravalvular regurgitation was more frequent after TAVR and was associated with increased late mortality. (Funded by Edwards Lifesciences; ClinicalTrials.gov number, NCT00530894.)

Stratification of Outcomes After Transcatheter Aortic Valve Replacement According to Surgical Inoperability for Technical Versus Clinical Reasons

ObjectivesThe goal of this study was to examine the impact of reasons for surgical inoperability on outcomes in patients undergoing transcatheter aortic valve replacement (TAVR).BackgroundPatients with severe aortic stenosis may be deemed inoperable due to technical or clinical reasons. The relative impact of each designation on early and late outcomes after TAVR is unclear.MethodsPatients were studied from the inoperable arm (cohort B) of the randomized PARTNER (Placement of Aortic Transcatheter Valve) trial and the nonrandomized continued access registry. Patients were classified according to whether they were classified as technically inoperable (TI) or clinically inoperable (CLI). Reasons for TI included porcelain aorta, previous mediastinal radiation, chest wall deformity, and potential for injury to previous bypass graft on sternal re-entry. Reasons for CLI were systemic factors that were deemed to make survival unlikely.ResultsOf the 369 patients, 23.0% were considered inoperable for technical reasons alone; the remaining were judged to be CLI. For TI, the most common cause was a porcelain aorta (42%); for CLI, it was multiple comorbidities (48%) and frailty (31%). Quality of life and 2-year mortality were significantly better among TI patients compared with CLI patients (mortality 23.3% vs. 43.8%; p < 0.001). Nonetheless, TAVR led to substantial survival benefits compared with standard therapy in both inoperable cohorts.ConclusionsPatients undergoing TAVR based solely on TI have better survival and quality of life improvements than those who are inoperable due to clinical comorbidities. Both TI and CLI TAVR have significant survival benefit in the context of standard therapy. (THE PARTNER TRIAL: Placement of AoRTic TraNscathetER Valve Trial; NCT00530894

Cellular Postconditioning: Allogeneic Cardiosphere-Derived Cells Reduce Infarct Size and Attenuate Microvascular Obstruction When Administered After Reperfusion in Pigs With Acute Myocardial Infarction

Intracoronary (IC) delivery of cardiosphere-derived cells (CDCs) has been demonstrated to be safe and effective in porcine and human chronic myocardial infarction (MI). However, IC delivery of CDCs after reperfusion in acute MI has never been assessed in a clinically-relevant large animal model. We tested CDCs as adjunctive therapy to reperfusion in a porcine model of MI