RESUMO
BACKGROUND: Adequate valve performance after surgical mitral valve repair with an annuloplasty ring is not always sustained over time. The risk of repeat mitral valve surgery may be high in these patients. Transcatheter mitral valve-in-ring (MViR) is emerging as an alternative for high-risk patients. OBJECTIVES: The authors sought to assess contemporary outcomes of MViR using third-generation balloon-expandable aortic transcatheter heart valves. METHODS: Patients who underwent MViR and were enrolled in the STDS/ACC TVT (Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy) Registry between August 2015 and December 2022 were analyzed. RESULTS: A total of 820 patients underwent MViR at 236 sites, mean age was 72.2 ± 10.4 years, 50.9% were female, mean STS score was 8.2% ± 6.9%, and most (78%) were in NYHA functional class III to IV. Mean left ventricular ejection fraction was 47.8% ± 14.2%, mean mitral gradient was 8.9 ± 7.0 mm Hg, and 75.5% had ≥ moderate mitral regurgitation. Access was transseptal in 93.9% with 88% technical success. All-cause mortality at 30 days was 8.3%, and at 1 year, 22.4%, with a reintervention rate of 9.1%. At 1-year follow-up, 75.6% were NYHA functional class I to II, Kansas City Cardiomyopathy Questionnaire score increased by 25.9 ± 29.1 points, mean mitral valve gradient was 8.4 ± 3.4 mm Hg, and 91.7% had ≤ mild mitral regurgitation. CONCLUSIONS: MViR with third-generation balloon-expandable aortic transcatheter heart valves is associated with a significant reduction in mitral regurgitation and improvement in symptoms at 1 year, but with elevated valvular gradients and a high reintervention rate. MViR is a reasonable alternative for high-risk patients unable undergo surgery who have appropriate anatomy for the procedure. (STS/ACC TVT Registry Mitral Module [TMVR]; NCT02245763).
Assuntos
Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Insuficiência da Valva Mitral , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/cirurgia , Insuficiência da Valva Mitral/etiologia , Volume Sistólico , Resultado do Tratamento , Função Ventricular Esquerda , Cateterismo Cardíaco/métodosRESUMO
BACKGROUND: Surgery remains the only recommended intervention for patients with native aortic regurgitation. A transcatheter therapy to treat patients at high risk for mortality and complications with surgical aortic valve replacement represents an unmet need. Commercial transcatheter heart valves in pure aortic regurgitation are hampered by unacceptable rates of embolisation and paravalvular regurgitation. The Trilogy transcatheter heart valve (JenaValve Technology, Irvine, CA, USA) provides a treatment option for these patients. We report outcomes with transfemoral transcatheter aortic valve implantation (TAVI) in patients with pure aortic regurgitation using this dedicated transcatheter heart valve. METHODS: The ALIGN-AR trial is a prospective, multicentre, single-arm study. We recruited symptomatic patients (aged ≥18 years) with moderate-to-severe or severe aortic regurgitation at high risk for mortality and complications after surgical aortic valve replacement at 20 US sites for treatment with the Trilogy transcatheter heart valve. The 30-day composite primary safety endpoint was compared for non-inferiority with a prespecified performance goal of 40·5%. The primary efficacy endpoint was 1-year all-cause mortality compared for non-inferiority with a performance goal of 25%. This trial is registered with ClinicalTrials.gov, NCT04415047, and is ongoing. FINDINGS: Between June 8, 2018, and Aug 29, 2022, we screened 346 patients. We excluded 166 (48%) patients and enrolled 180 (52%) patients with symptomatic aortic regurgitation deemed high risk by the heart team and independent screening committee assessments. The mean age of the study population was 75·5 years (SD 10·8), and 85 (47%) were female, 95 (53%) were male, and 131 (73%) were White. Technical success was achieved in 171 (95%) patients. At 30 days, four (2%) deaths, two (1%) disabling strokes, and two (1%) non-disabling strokes occurred. Using standard Valve Academic Research Consortium-2 definitions, the primary safety endpoint was achieved, with events occurring in 48 (27% [97·5% CI 19·2-34·0]) patients (pnon-inferiority<0·0001), with new pacemaker implantation in 36 (24%) patients. The primary efficacy endpoint was achieved, with mortality in 14 (7·8% [3·3-12·3]) patients at 1 year (pnon-inferiority<0·0001). INTERPRETATION: This study shows the safety and effectiveness of treating native aortic regurgitation using a dedicated transcatheter heart valve to treat patients with symptomatic moderate-to-severe or severe aortic regurgitation who are at high risk for mortality or complications after surgical aortic valve replacement. The observed short-term clinical and haemodynamic outcomes are promising as are signs of left ventricular remodelling, but long-term follow-up is necessary. FUNDING: JenaValve Technology.
Assuntos
Insuficiência da Valva Aórtica , Estenose da Valva Aórtica , Próteses Valvulares Cardíacas , Substituição da Valva Aórtica Transcateter , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Insuficiência da Valva Aórtica/etiologia , Insuficiência da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/cirurgia , Estudos Prospectivos , Desenho de Prótese , Fatores de Risco , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: The MITRAL (Mitral Implantation of Transcatheter Valves) trial is the first prospective trial to evaluate the safety and feasibility of balloon-expandable aortic transcatheter heart valves in patients with failed surgical bioprostheses or annuloplasty rings and severe mitral annular calcification treated with mitral valve-in-valve (MViV), valve-in-ring (MViR), or valve-in-mitral annular calcification (ViMAC). OBJECTIVES: The aim of this study was to evaluate 5-year outcomes among these patients. METHODS: A multicenter prospective study was conducted among patients at high surgical risk at 13 U.S. sites. Patients underwent MViV (n = 30), MViR (n = 30), or ViMAC (n = 31) and were followed annually for 5 years. Kansas City Cardiomyopathy Questionnaire scores were obtained at baseline and follow-up visits. Echocardiograms were analyzed at independent core laboratories. RESULTS: A total of 91 patients underwent transcatheter mitral valve replacement (February 2015 to December 2017). The mean age was 74.3 ± 8.9 years. At 5-year follow-up, the lowest all-cause mortality was observed in the MViV group (21.4%), 94.7% of patients were in NYHA functional class I or II, and the mean mitral gradient was 6.6 ± 2.5 mm Hg. The MViR and ViMAC groups had higher all-cause mortality (65.5% and 67.9%), most survivors were in NYHA functional classes I and II (50% and 55.6%), and mean mitral gradients remained stable (5.8 ± 0.1 and 6.7 ± 2.5 mm Hg). Significant improvements in Kansas City Cardiomyopathy Questionnaire scores were observed when all 3 arms were pooled. CONCLUSIONS: MViV, MViR, and ViMAC procedures were associated with sustained improvement of heart failure symptoms and quality of life among survivors at 5 years. Transcatheter heart valve function remained stable in all 3 groups. Patients treated with MViV had excellent survival at 5 years, whereas survival was lower in the MViR and ViMAC groups, consistent with underlying disease severity. Patients with more residual mitral regurgitation had higher mortality.
Assuntos
Calcinose , Cardiomiopatias , Doenças das Valvas Cardíacas , Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Insuficiência da Valva Mitral , Doenças Vasculares , Humanos , Idoso , Idoso de 80 Anos ou mais , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Estudos Prospectivos , Qualidade de Vida , Resultado do Tratamento , Cateterismo Cardíaco/métodos , Doenças das Valvas Cardíacas/diagnóstico por imagem , Doenças das Valvas Cardíacas/cirurgia , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/cirurgia , Insuficiência da Valva Mitral/etiologia , Calcinose/cirurgia , Doenças Vasculares/etiologiaRESUMO
BACKGROUND AND OBJECTIVES: Ocedurenone (KBP-5074) is a novel nonsteroidal mineralocorticoid receptor antagonist that has demonstrated safety and efficacy in clinical trials in patients with uncontrolled hypertension and stage 3b/4 chronic kidney disease. This study evaluated the involvement of cytochrome P450 (CYP) isozymes and drug transporters in the biotransformation of ocedurenone, and whether ocedurenone inhibited or induced CYP enzymes and transporters. Clinical pharmacokinetic drug-drug interaction (DDI) of ocedurenone with CYP3A inhibitor and inducer were investigated in healthy volunteers. METHODS: In vitro tests were conducted to determine which CYP enzymes were involved in ocedurenone's metabolism and whether ocedurenone inhibited or induced these CYP enzymes; ocedurenone substrate characteristics for efflux and uptake transporters and its inhibitory potential on major drug transporters were also assessed. A clinical DDI study was conducted in healthy volunteers to evaluate the effects of a strong CYP3A inhibitor (itraconazole) and inducer (rifampin) on ocedurenone's pharmacokinetics. RESULTS: The in vitro study showed that ocedurenone was primarily metabolized by CYP3A4 and that it did not inhibit CYP enzymes. Ocedurenone appeared to be a substrate of BCRP and P-gp efflux transporters and inhibited BCRP, BSEP, MDR1, MATE1 and 2-K, OATP1B1/3, and OCT1. The clinical DDI study showed that itraconazole reduced ocedurenone's oral clearance by 51% and increased area under the plasma concentration-time curve extrapolated to infinity (AUC0-inf) by 104%, while rifampin increased its oral clearance by 6.4-fold and decreased plasma AUC0-inf by 84%. CONCLUSION: Ocedurenone was shown to be a CYP3A substrate, with no inhibition potential on major drug metabolizing CYP enzymes and transporters at clinical efficacious doses. Ocedurenone did not induce CYP1A2 and 3A4 activity in cultured human primary hepatocytes. Clinical DDI study indicated ocedurenone was well tolerated when administered as a single 0.5-mg dose both alone and with itraconazole or rifampin, and while itraconazole had a weak effect on ocedurenone's pharmacokinetics, rifampin had a significant effect reducing systemic exposures.
Assuntos
Inibidores do Citocromo P-450 CYP3A , Rifampina , Humanos , Inibidores do Citocromo P-450 CYP3A/farmacologia , Itraconazol/farmacologia , Indutores do Citocromo P-450 CYP3A/farmacocinética , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Área Sob a Curva , Proteínas de Neoplasias , Sistema Enzimático do Citocromo P-450/metabolismo , Interações Medicamentosas , Citocromo P-450 CYP3A/metabolismoRESUMO
The prevalence of concurrent cancer and severe aortic stenosis (AS) is increasing due to an ageing population. In addition to shared traditional risk factors for AS and cancer, patients with cancer may be at increased risk for AS due to off-target effects of cancer-related therapy, such as mediastinal radiation therapy (XRT), as well as shared non-traditional pathophysiological mechanisms. Compared with surgical aortic valve replacement, major adverse events are generally lower in patients with cancer undergoing transcatheter aortic valve intervention (TAVI), especially in those with history of mediastinal XRT. Similar procedural and short-to-intermediate TAVI outcomes have been observed in patients with cancer as compared with no cancer, whereas long-term outcomes are dependent on cancer survival. Considerable heterogeneity exists between cancer subtypes and stage, with worse outcomes observed in those with active and advanced-stage disease as well as specific cancer subtypes. Procedural management in patients with cancer poses unique challenges and thus requires periprocedural expertise and close collaboration with the referring oncology team. The decision to ultimately pursue TAVI involves a multidisciplinary and holistic approach in assessing the appropriateness of intervention. Further clinical trial and registry studies are needed to better appreciate outcomes in this population.
Assuntos
Estenose da Valva Aórtica , Implante de Prótese de Valva Cardíaca , Neoplasias , Substituição da Valva Aórtica Transcateter , Humanos , Valva Aórtica/cirurgia , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia , Substituição da Valva Aórtica Transcateter/efeitos adversos , Fatores de Risco , Implante de Prótese de Valva Cardíaca/efeitos adversos , Neoplasias/complicações , Neoplasias/terapiaRESUMO
The removal of intramyocardial masses has long been thought of as a surgical procedure and is generally reserved for patients with obstructive symptoms when the mass is thought to be benign. Thus, many patients who are incidentally diagnosed with intracardiac masses are either subjected to protracted follow-up with serial imaging awaiting tumor growth before surgical excision is ultimately offered. We report a novel procedure in which a 54-year-old man with an atrial myxoma underwent successful percutaneous resection using electrosurgery followed by removal with a novel endovascular retrieval system. This approach provides an alternative to either surgical excision or watchful waiting in patients with small- to medium-sized intracardiac tumors. (Level of Difficulty: Advanced.).
RESUMO
BACKGROUND: The MITRAL (Mitral Implantation of Transcatheter Valves) trial is the first prospective study for valve-in-mitral annular calcification (ViMAC), mitral valve-in-ring (MViR), and mitral valve-in-valve (MViV) using balloon-expandable aortic transcatheter heart valves. Procedural outcomes beyond 1 year are not well described. OBJECTIVES: This study evaluated 2-year outcomes in ViMAC, MViR, and MViV in the MITRAL trial. METHODS: This multicenter prospective study enrolled patients with severe MAC, prior failed mitral annuloplasty ring repair, or prior failed bioprosthetic MV replacement who were at high surgical risk at 13 U.S. sites. RESULTS: Between February 1, 2015, and December 31, 2017, 91 patients were enrolled (31 with ViMAC, 30 with MViR, and 30 with MViV). In the ViMAC group, 2-year all-cause mortality was 39.3%, 66.7% were New York Heart Association (NYHA) functional class I-II, and mean MV gradient was 5.6 ± 2.0 mm Hg. In the MViR group, 2-year all-cause mortality was 50%, 65% were NYHA functional class I-II, and mean MV gradient was 6.5 ± 2.7 mm Hg. In the MViV group, 2-year all-cause mortality was 6.7%, 85% were NYHA functional class I-II, and mean MV gradient was 6.9 ± 2.4 mm Hg. At 2 years, all patients had ≤mild mitral regurgitation and survivors in all 3 arms showed sustained improvement in Kansas City Cardiomyopathy Questionnaire scores compared to baseline. CONCLUSIONS: Use of balloon-expandable aortic transcatheter heart valves in selected patients with severe MAC, failed annuloplasty ring, and bioprosthetic MV dysfunction is associated with improvements in symptoms, quality of life, and stable prosthesis function at 2-year follow-up. Between 1 and 2 years, the MViR group experienced higher mortality rates than the MViV and ViMAC groups.
Assuntos
Bioprótese , Calcinose , Humanos , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Estudos Prospectivos , Qualidade de Vida , Calcinose/cirurgiaRESUMO
BACKGROUND: Tricuspid regurgitation (TR) is prevalent and undertreated, with mortality and morbidity increasing with TR severity. Given poor outcomes with medical therapy and high in-hospital mortality for isolated tricuspid valve surgery, emerging transcatheter repair devices offer a promising alternative. OBJECTIVES: The Edwards Cardioband Tricuspid Valve Reconstruction System Early Feasibility study (NCT03382457) evaluates the treatment of functional TR via annular reduction with the Cardioband Tricuspid Valve Reconstruction System (Edwards Lifesciences). METHODS: Patients with ≥ moderate functional TR were eligible for this prospective, single-arm multicenter study. At 1 year, patients were evaluated for echocardiographic parameters, clinical and quality-of-life measures, and major adverse events. RESULTS: The 37 patients enrolled had a mean age of 78 years; 76% were female; and they had ≥ severe functional (97.3%) or mixed (2.7%) TR, atrial flutter/fibrillation (97%), and New York Heart Association functional class III/IV (65%). At 1 year, 73.0% achieved ≤ moderate TR (P < 0.0001), and 73.1% had ≥2 grade reductions. Echocardiography showed significant reductions in the tricuspid annulus diameter (P < 0.0001), mean vena contracta (P < 0.0001), proximal isovelocity surface area effective regurgitant orifice area (P < 0.0001), right ventricular end-diastolic diameter (P < 0.0001), and inferior vena contracta (P = 0.0006). New York Heart Association functional class improved significantly (P < 0.0001), with 92.3% achieving class I/II, and Kansas City Cardiomyopathy Questionnaire scores improved by 19.0 points (P < 0.0001). One-year cardiovascular mortality was 8.1%, reinterventions were necessary in 5.4%, major access site complications occurred in 8.1%, and severe bleeding was noted in 35.1% of patients. Kaplan-Meier estimates of survival and freedom from heart failure rehospitalization were 85.9% and 88.7%, respectively. CONCLUSIONS: One-year experience using the Cardioband system for tricuspid valve repair shows high survival and low rehospitalization rates with durable outcomes in TR reduction and echocardiographic, clinical, and quality-of-life outcomes.
Assuntos
Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Tricúspide , Idoso , Cateterismo Cardíaco , Estudos de Viabilidade , Feminino , Humanos , Masculino , Estudos Prospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Valva Tricúspide/diagnóstico por imagem , Valva Tricúspide/cirurgia , Insuficiência da Valva Tricúspide/diagnóstico por imagem , Insuficiência da Valva Tricúspide/cirurgiaRESUMO
BACKGROUND: Coronary artery disease leads to stenosis of the major cardiac vessels, resulting in ischemia and infarction. Percutaneous intervention (PCI) with balloon angioplasty can re-open stenosed vessels. Drug eluting stents (DES) and intravascular brachytherapy (IVBT) and drug-coated balloons (DCBs) are proven to decrease the likelihood of another restenosis after PCI, but neither is completely effective. Due to the limited long-term effectiveness of IVBT or DCB used separately for salvage PCI, we combined the two in some poor prognosis patients. METHODS: Combined IVBT+DCB was intended for a total of 36 patients from 2015-2020. PCI with some combination of ballooning, laser and directional/rotational atherectomy was used to maximally open the stenotic region prior to IVBT+DCB. Beta-radiation brachytherapy for all patients was done with a Novoste Beta-Cath. Lutonix 4.0 x 40 mm paclitaxel-coated balloons (Bard, Murray Hill, NJ) were employed. RESULTS: Overall survival at two years was 88%. Nine patients had follow-up angiograms, all for cardiac symptoms. Time from IVBT+DCB to follow-up angiography ranged from 4 to 33 months. The average months PCI-free interval before brachy therapy was 11.1 mos (95% CI 1.03-23.25) versus 23.3 mos after VBT (23.3 95% CI 12.3-32.3). The mean difference was 11.2 mos (95% CI 1.06-21.4, p < 0.031). None of the follow-up angiographic procedures displayed evidence of what could be interpreted as radiation damage. CONCLUSIONS: In this uncontrolled series, IVBT plus DCB appeared to lengthen the ISR-free interval relative to what had been achieved prior to the combined intervention. We view these results as mildly encouraging, worthy of further study.
Assuntos
Braquiterapia , Reestenose Coronária , Intervenção Coronária Percutânea , Preparações Farmacêuticas , Braquiterapia/métodos , Reestenose Coronária/radioterapia , Humanos , Stents , Resultado do TratamentoRESUMO
BACKGROUND: Coronary artery obstruction is a rare, devastating complication of transcatheter aortic valve replacement. Transcatheter electrosurgical aortic leaflet laceration (Bioprosthetic or Native Aortic Scallop Intentional Laceration to Prevent Iatrogenic Coronary Artery Obstruction [BASILICA]) is a novel technique to prevent coronary artery obstruction. We report the 1-year outcomes of the BASILICA trial. Primary end points of 30-day success and safety have been reported previously. METHODS: The BASILICA trial was a prospective, multicenter, single-arm safety and feasibility study. Subjects with severe native or bioprosthetic aortic valve disease at high or extreme risk for surgery, and high risk of coronary artery obstruction, were included. End points at 1 year included death, stroke, and myocardial infarction. Source data was independently verified and end points independently adjudicated. RESULTS: Thirty subjects were enrolled between February 2018 and July 2018. At 30 days, BASILICA was successful in 28 subjects (93.3%), there were 3 strokes (10%), including 1 disabling stroke (3.3%), 1 death (3.3%), and 1 periprocedural myocardial infarction (3.3%). Between 30 days and 1 year, there were no additional strokes, no myocardial infarction, and 2 deaths (10% 1-year mortality). No subject needed repeat intervention for aortic valve or coronary disease. Two subjects had infective endocarditis (6.7%), but neither was isolated to the aortic valve. There were no hospital admissions for heart failure. Fourteen (46.7%) subjects required repeat hospital admission for other causes. Aortic valve gradients on echocardiography, New York Heart Association functional class, and Kansas City Cardiomyopathy Questionnaire scores improved from baseline to 30 days and were maintained at 1 year. CONCLUSIONS: In these subjects with multiple comorbidities and restrictive anatomy that underwent transcatheter aortic valve replacement, there was no late stroke, myocardial infarction, or death related to BASILICA. Mitigation of coronary obstruction remained intact at 1 year and was not related to recurrent readmission. These results are reassuring for patients and physicians who wish to avoid the long-term complications related to snorkel stenting. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03381989.
Assuntos
Estenose da Valva Aórtica , Bioprótese , Próteses Valvulares Cardíacas , Lacerações , Substituição da Valva Aórtica Transcateter , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Eletrocirurgia , Humanos , Estudos Prospectivos , Desenho de Prótese , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do TratamentoRESUMO
Concerns over radiation exposure are ubiquitous to all interventional cardiologists; however, fear of exposure during childbearing years disproportionately deters women from entering the field. This review summarizes the available data on occupational radiation exposure during pregnancy with an emphasis on radiation quantification, the impact of exposure at various stages of fetal development, societal recommendations for safe levels of exposure during gestation, threshold levels necessary to induce fetal harm, and safe practices for the pregnant interventionalist. Reconciling the available information, we conclude that pregnancy in the cardiac catheterization laboratory is both safe and feasible. This review also highlights new technologies that may augment standard radiation safety techniques and are of particular interest to the pregnant interventional cardiologist. Finally, we propose steps to improve female representation in this field, underscoring the importance of a sex-balanced workforce.
Assuntos
Cardiologia , Exposição Ocupacional , Exposição à Radiação , Cateterismo Cardíaco/efeitos adversos , Feminino , Humanos , Laboratórios , Exposição Ocupacional/efeitos adversos , Gravidez , Doses de Radiação , Exposição à Radiação/efeitos adversos , Exposição à Radiação/prevenção & controle , Radiografia IntervencionistaRESUMO
BACKGROUND: In low surgical risk patients with symptomatic severe aortic stenosis, the PARTNER 3 (Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low Risk Patients With Aortic Stenosis) trial demonstrated superiority of transcatheter aortic valve replacement (TAVR) versus surgery for the primary endpoint of death, stroke, or re-hospitalization at 1 year. OBJECTIVES: This study determined both clinical and echocardiographic outcomes between 1 and 2 years in the PARTNER 3 trial. METHODS: This study randomly assigned 1,000 patients (1:1) to transfemoral TAVR with the SAPIEN 3 valve versus surgery (mean Society of Thoracic Surgeons score: 1.9%; mean age: 73 years) with clinical and echocardiography follow-up at 30 days and at 1 and 2 years. This study assessed 2-year rates of the primary endpoint and several secondary endpoints (clinical, echocardiography, and quality-of-life measures) in this as-treated analysis. RESULTS: Primary endpoint follow-up at 2 years was available in 96.5% of patients. The 2-year primary endpoint was significantly reduced after TAVR versus surgery (11.5% vs. 17.4%; hazard ratio: 0.63; 95% confidence interval: 0.45 to 0.88; p = 0.007). Differences in death and stroke favoring TAVR at 1 year were not statistically significant at 2 years (death: TAVR 2.4% vs. surgery 3.2%; p = 0.47; stroke: TAVR 2.4% vs. surgery 3.6%; p = 0.28). Valve thrombosis at 2 years was increased after TAVR (2.6%; 13 events) compared with surgery (0.7%; 3 events; p = 0.02). Disease-specific health status continued to be better after TAVR versus surgery through 2 years. Echocardiographic findings, including hemodynamic valve deterioration and bioprosthetic valve failure, were similar for TAVR and surgery at 2 years. CONCLUSIONS: At 2 years, the primary endpoint remained significantly lower with TAVR versus surgery, but initial differences in death and stroke favoring TAVR were diminished and patients who underwent TAVR had increased valve thrombosis. (Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low Risk Patients With Aortic Stenosis [PARTNER 3]; NCT02675114).
Assuntos
Estenose da Valva Aórtica/mortalidade , Estenose da Valva Aórtica/cirurgia , Complicações Pós-Operatórias/mortalidade , Substituição da Valva Aórtica Transcateter/mortalidade , Substituição da Valva Aórtica Transcateter/tendências , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Masculino , Complicações Pós-Operatórias/diagnóstico por imagem , Fatores de Risco , Taxa de Sobrevida/tendências , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: We sought to assess in-hospital and long-term outcomes of retrograde compared with antegrade-only percutaneous coronary intervention for chronic total occlusion (CTO PCI). BACKGROUND: Procedural and clinical outcomes following retrograde compared with antegrade-only CTO PCI remain unknown. METHODS: Using the core-lab adjudicated OPEN-CTO registry, we compared the outcomes of retrograde to antegrade-only CTO PCI. Primary endpoints included were in-hospital major adverse cardiac and cerebrovascular events (MACCE) (all-cause death, stroke, myocardial infarction [MI], emergency cardiac surgery, or clinically significant perforation) and MACCE at 1-year (all-cause death, MI, stroke, target lesion revascularization, or target vessel reocclusion). RESULTS: Among 885 single CTO procedures from the OPEN-CTO registry, 454 were retrograde and 431 were antegrade-only. Lesion complexity was higher (J-CTO score: 2.7 vs. 1.9; p < .001) and technical success lower (82.4 vs. 94.2%; p < .001) in retrograde compared with antegrade-only procedures. All-cause death was higher in the retrograde group in-hospital (2 vs. 0%; p = .003), but not at 1-year (4.9 vs. 3.3%; p = .29). Compared with antegrade-only procedures, in-hospital MACCE rates (composite of all-cause death, stroke, MI, emergency cardiac surgery, and clinically significant perforation) were higher in the retrograde group (10.8 vs. 3.3%; p < .001) and at 1-year (19.5 vs. 13.9%; p = .03). In sensitivity analyses landmarked at discharge, there was no difference in MACCE rates at 1 year following retrograde versus antegrade-only CTO PCI. Improvements in Seattle Angina Questionnaire Quality of Life scores at 1-year were similar between the retrograde and antegrade-only groups (29.9 vs 30.4; p = .58). CONCLUSIONS: In the OPEN-CTO registry, retrograde CTO procedures were associated with higher rates of in-hospital MACCE compared with antegrade-only; however, post-discharge outcomes, including quality of life improvements, were similar between technical modalities.
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Oclusão Coronária , Intervenção Coronária Percutânea , Assistência ao Convalescente , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/cirurgia , Humanos , Alta do Paciente , Intervenção Coronária Percutânea/efeitos adversos , Qualidade de Vida , Sistema de Registros , Resultado do TratamentoRESUMO
BACKGROUND: We sought to describe the outcomes of patients who underwent caval valve implantation (CAVI) for treatment of severe tricuspid regurgitation (TR) in the United States. Previous studies on CAVI have used a variety of techniques and transcatheter valves. We present our findings from CAVI with inferior vena cava (IVC) implant only using a single valve. METHODS: Patients who were determined to be poor candidates for tricuspid valve surgery and underwent CAVI in the United States from March 1, 2013 through March 1, 2018 were included in this study. Data during hospitalizations and interim outpatient follow-up from each individual site were collected and entered into a central password-protected database. RESULTS: A total of 24 patients were treated. The median age was 79.5 years, 63% were women, and 96% were white. Twenty-three of 24 patients underwent valve implantation with a 29 mm Sapien 3 valve (Edwards Lifesciences). There was a 100% rate of successful valve implantation. There were no cases requiring emergency surgery. Thirty-day mortality rate was 25%. The median survival as of last follow-up of all patients was 350 days. Pre- and postprocedure New York Heart Association (NYHA) class data were available in 11 of 24 patients; of these 11 patients, 72.7% improved at least 1 NYHA class from baseline. CONCLUSION: CAVI may be performed safely in a high surgical risk population with severe tricuspid regurgitation. Dedicated studies with longer-term follow-up are needed.
Assuntos
Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Insuficiência da Valva Tricúspide , Idoso , Cateterismo Cardíaco , Feminino , Humanos , Masculino , Desenho de Prótese , Sistema de Registros , Índice de Gravidade de Doença , Resultado do Tratamento , Valva Tricúspide/diagnóstico por imagem , Valva Tricúspide/cirurgia , Insuficiência da Valva Tricúspide/diagnóstico , Insuficiência da Valva Tricúspide/epidemiologia , Insuficiência da Valva Tricúspide/cirurgia , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Intentional laceration of the anterior mitral leaflet (LAMPOON) is an effective adjunct to transcatheter mitral valve replacement that prevents left ventricular outflow tract (LVOT) obstruction. To date, LAMPOON has been performed in over 150 patients using a retrograde approach that can be technically challenging. A modified antegrade transseptal technique may simplify the procedure. METHODS: Antegrade LAMPOON was developed and tested in nonsurvival pig experiments. Thereafter, antegrade LAMPOON was performed in patients at prohibitive risk of LVOT obstruction. Clinical, procedural, and angiographic details were abstracted from medical records of their index procedure, and were compared with findings in comparable patients at risk of fixed-LVOT obstruction in the LAMPOON investigational device exemption trial. RESULTS: Eight patients at risk of fixed LVOT obstruction underwent antegrade LAMPOON. Leaflet traversal and laceration were technically successful in all. There were no cases of clinically significant LVOT obstruction (mean LVOT gradient at discharge: 5.4±1.4 mm Hg). One patient suffered a ventricular wire perforation, unrelated to the antegrade LAMPOON technique, and did not survive to discharge. At the time of discharge, no patients had an increase of >10 mm Hg in LVOT gradient compared with baseline. Procedure times (from traversal to transcatheter mitral valve replacement) were shorter, compared with the retrograde technique in the LAMPOON investigational device exemption trial (39±09 versus 65±35 minutes). All patients survived (8/8, 100%) the procedure, and 7/8 (88%) survived to 30 days, similar to subjects in the LAMPOON investigational device exemption trial. CONCLUSIONS: Antegrade LAMPOON is an effective, reproducible, and simplified strategy to lacerate the anterior leaflet before transcatheter mitral valve replacement. The authors recommend the technique as the new standard for LAMPOON.
Assuntos
Cateterismo Cardíaco , Procedimentos Cirúrgicos Cardíacos , Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral/cirurgia , Estenose da Valva Mitral/cirurgia , Valva Mitral/cirurgia , Obstrução do Fluxo Ventricular Externo/prevenção & controle , Animais , Cateterismo Cardíaco/efeitos adversos , Cateterismo Cardíaco/instrumentação , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Feminino , Próteses Valvulares Cardíacas , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/instrumentação , Humanos , Masculino , Valva Mitral/fisiopatologia , Insuficiência da Valva Mitral/fisiopatologia , Estenose da Valva Mitral/fisiopatologia , Modelos Animais , Duração da Cirurgia , Estudos Retrospectivos , Fatores de Risco , Sus scrofa , Pesquisa Translacional Biomédica , Resultado do Tratamento , Obstrução do Fluxo Ventricular Externo/etiologia , Obstrução do Fluxo Ventricular Externo/fisiopatologiaRESUMO
BACKGROUND: Subclinical leaflet thrombosis, characterized by hypoattenuated leaflet thickening (HALT) and reduced leaflet motion observed on 4-dimensional computed tomography (CT), may represent a form of bioprosthetic valve dysfunction. OBJECTIVES: The U.S. Food and Drug Administration mandated CT studies to understand the natural history of this finding, differences between transcatheter and surgical valves, and its association with valve hemodynamics and clinical outcomes. METHODS: The PARTNER 3 (The Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low-Risk Patients With Aortic Stenosis) CT substudy randomized 435 patients with low-surgical-risk aortic stenosis to undergo transcatheter aortic valve replacement (n = 221) or surgery (n = 214). Serial 4-dimensional CTs were performed at 30 days and 1 year and were analyzed independently by a core laboratory. RESULTS: The incidence of HALT increased from 10% at 30 days to 24% at 1 year. Spontaneous resolution of 30-day HALT occurred in 54% of patients at 1 year, whereas new HALT appeared in 21% of patients at 1 year. HALT was more frequent in transcatheter versus surgical valves at 30 days (13% vs. 5%; p = 0.03), but not at 1 year (28% vs. 20%; p = 0.19). The presence of HALT did not significantly affect aortic valve mean gradients at 30 days or 1 year. Patients with HALT at both 30 days and 1 year, compared with those with no HALT at 30 days and 1 year, had significantly increased aortic valve gradients at 1 year (17.8 ± 2.2 mm Hg vs. 12.7. ± 0.3 mm Hg; p = 0.04). CONCLUSIONS: Subclinical leaflet thrombosis was more frequent in transcatheter compared with surgical valves at 30 days, but not at 1 year. The impact of HALT on thromboembolic complications and structural valve degeneration needs further assessment.
Assuntos
Estenose da Valva Aórtica/cirurgia , Bioprótese/efeitos adversos , Próteses Valvulares Cardíacas/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Trombose/epidemiologia , Substituição da Valva Aórtica Transcateter/efeitos adversos , Idoso , Canadá/epidemiologia , Feminino , Tomografia Computadorizada Quadridimensional , Humanos , Masculino , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Trombose/diagnóstico por imagem , Trombose/etiologia , Substituição da Valva Aórtica Transcateter/mortalidade , Estados Unidos/epidemiologiaRESUMO
Background Patient selection and outcomes for percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) have changed over the past decade. However, there is limited information on outcomes for both revascularization strategies in the same population. The study evaluated temporal changes in risk profile, procedural characteristics, and clinical outcomes for PCI- and CABG-treated patients. Methods and Results We analyzed all PCI and isolated CABG between 2005 and 2017 in nonfederal hospitals in Washington State. Descriptive analysis was performed to evaluate temporal changes in risk profile and, risk-adjusted in-hospital mortality. Over the study period, 178 474 PCI and 36 592 CABG procedures were performed. PCI and CABG volume decreased by 2.9% and 22.6%, respectively. Compared with 2005-2009, patients receiving either form of revascularization between 2014 and 2017 had a higher prevalence of comorbidities including diabetes mellitus and hypertension and dialysis. Presentation with ST-segment-elevation myocardial infarction (17% versus 20%) and cardiogenic shock (2.4% versus 3.4%) increased for patients with PCI compared with CABG. Conversely, clinical acuity decreased for patients receiving CABG over the study period. From 2005 to 2017, mean National Cardiovascular Data Registry CathPCI mortality score increased for patients treated with PCI (20.1 versus 22.4, P<0.0001) and decreased for patients treated with CABG (18.8 versus 17.8, P<0.0001). Adjusted observed/expected in-hospital mortality ratio increased for PCI (0.98 versus 1.19, P<0.0001) but decreased for CABG (1.21 versus 0.74, P<0.0001) over the study period. Conclusions Clinical acuity increased for patients treated with PCI rather than CABG. This resulted in an increase in adjusted observed/expected mortality ratio for patients undergoing PCI and a decrease for CABG. These shifts may reflect an increased use of PCI instead of CABG for patients considered to be at high surgical risk.
Assuntos
Ponte de Artéria Coronária/tendências , Doença da Artéria Coronariana/terapia , Avaliação de Processos e Resultados em Cuidados de Saúde/tendências , Intervenção Coronária Percutânea/tendências , Padrões de Prática Médica/tendências , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/mortalidade , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Bases de Dados Factuais , Feminino , Mortalidade Hospitalar/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , WashingtonRESUMO
Importance: Medically treated symptomatic severe aortic stenosis has poor outcomes, and in the past 6 decades, it has successfully been treated with surgical aortic valve replacement (SAVR). However, one-third of patients with indications for SAVR are not offered surgery because of the high risk of complications. Transcatheter aortic valve replacement (TAVR), initially developed as a less invasive treatment for inoperable patients, has successfully been used in healthier patient cohorts. In 2017, TAVR became the most common approach for aortic valve replacement in the United States. Observations: During the past decade, the Placement of Aortic Transcatheter Valve (PARTNER) trials (for balloon-expandable valves) and the CoreValve trials (for self-expandable valves) investigated the performance of TAVR in progressively lower-risk patient cohorts. The initial trials demonstrated TAVR to be superior (PARTNER B) and noninferior (CoreValve Extreme Risk) to optimal medical therapy in inoperable patients. Subsequent trials showed both balloon-expandable and self-expandable valves to have good results in high-risk, medium-risk, and low-risk surgical patients when compared with SAVR. However, owing to the fundamentally different nature of the procedure, some complications have been more prevalent with TAVR, most notably moderate or severe paravalvular leak, conduction abnormalities necessitating permanent pacemaker placement, and vascular complications. When present, these complications have been associated with worse outcomes. Conclusions and Relevance: The results of the groundbreaking TAVR trials from the past decade have led to a revolution in the treatment of aortic stenosis. There are now 3 US Food and Drug Administration-approved TAVR devices, and with the encouraging results from the latest low-risk trials, TAVR is likely going to become the dominant treatment for symptomatic severe aortic stenosis. New devices on the horizon are looking to improve the complication rates of TAVR, and ongoing trials are looking to further expand the indications of TAVR and answer 1 of the main remaining questions, ie, long-term durability of percutaneously placed devices.
Assuntos
Estenose da Valva Aórtica/cirurgia , Substituição da Valva Aórtica Transcateter , Ensaios Clínicos como Assunto , Próteses Valvulares Cardíacas , Humanos , Índice de Gravidade de Doença , Substituição da Valva Aórtica Transcateter/tendênciasRESUMO
The RAS/MAPK pathway is a major driver of oncogenesis and is dysregulated in approximately 30% of human cancers, primarily by mutations in the BRAF or RAS genes. The extracellular-signal-regulated kinases (ERK1 and ERK2) serve as central nodes within this pathway. The feasibility of targeting the RAS/MAPK pathway has been demonstrated by the clinical responses observed through the use of BRAF and MEK inhibitors in BRAF V600E/K metastatic melanoma; however, resistance frequently develops. Importantly, ERK1/2 inhibition may have clinical utility in overcoming acquired resistance to RAF and MEK inhibitors, where RAS/MAPK pathway reactivation has occurred, such as relapsed BRAF V600E/K melanoma. We describe our structure-based design approach leading to the discovery of AZD0364, a potent and selective inhibitor of ERK1 and ERK2. AZD0364 exhibits high cellular potency (IC50 = 6 nM) as well as excellent physicochemical and absorption, distribution, metabolism, and excretion (ADME) properties and has demonstrated encouraging antitumor activity in preclinical models.
Assuntos
Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Descoberta de Drogas , Imidazóis/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Pirazinas/uso terapêutico , Pirimidinas/farmacologia , Administração Oral , Animais , Antineoplásicos/administração & dosagem , Apoptose , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Proliferação de Células , Quimioterapia Combinada , Feminino , Humanos , Imidazóis/farmacologia , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Nus , Estrutura Molecular , Inibidores de Proteínas Quinases/administração & dosagem , Pirazinas/farmacologia , Pirimidinas/administração & dosagem , Pirimidinas/uso terapêutico , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Among patients with aortic stenosis who are at intermediate or high risk for death with surgery, major outcomes are similar with transcatheter aortic-valve replacement (TAVR) and surgical aortic-valve replacement. There is insufficient evidence regarding the comparison of the two procedures in patients who are at low risk. METHODS: We randomly assigned patients with severe aortic stenosis and low surgical risk to undergo either TAVR with transfemoral placement of a balloon-expandable valve or surgery. The primary end point was a composite of death, stroke, or rehospitalization at 1 year. Both noninferiority testing (with a prespecified margin of 6 percentage points) and superiority testing were performed in the as-treated population. RESULTS: At 71 centers, 1000 patients underwent randomization. The mean age of the patients was 73 years, and the mean Society of Thoracic Surgeons risk score was 1.9% (with scores ranging from 0 to 100% and higher scores indicating a greater risk of death within 30 days after the procedure). The Kaplan-Meier estimate of the rate of the primary composite end point at 1 year was significantly lower in the TAVR group than in the surgery group (8.5% vs. 15.1%; absolute difference, -6.6 percentage points; 95% confidence interval [CI], -10.8 to -2.5; P<0.001 for noninferiority; hazard ratio, 0.54; 95% CI, 0.37 to 0.79; P = 0.001 for superiority). At 30 days, TAVR resulted in a lower rate of stroke than surgery (P = 0.02) and in lower rates of death or stroke (P = 0.01) and new-onset atrial fibrillation (P<0.001). TAVR also resulted in a shorter index hospitalization than surgery (P<0.001) and in a lower risk of a poor treatment outcome (death or a low Kansas City Cardiomyopathy Questionnaire score) at 30 days (P<0.001). There were no significant between-group differences in major vascular complications, new permanent pacemaker insertions, or moderate or severe paravalvular regurgitation. CONCLUSIONS: Among patients with severe aortic stenosis who were at low surgical risk, the rate of the composite of death, stroke, or rehospitalization at 1 year was significantly lower with TAVR than with surgery. (Funded by Edwards Lifesciences; PARTNER 3 ClinicalTrials.gov number, NCT02675114.).