Point of care CYP2C19 genotyping after percutaneous coronary intervention.

Loss-of-function CYP2C19 variants are associated with increased cumulative ischemic outcomes warranting CYP2C19 genotyping prior to clopidogrel administration. TAILOR-PCI was an international, multicenter (40 sites), prospective, randomized trial comparing rapid point of care (POC) genotype-guided vs. conventional anti-platelet therapy. The performance of buccal-based rapid CYP2C19 genotyping performed by non-laboratory-trained staff in TAILOR-PCI was assessed. Pre-trial training and evaluation involved rapid genotyping of 373 oral samples, with 99.5% (371/373) concordance with Sanger sequencing. During TAILOR-PCI, 5302 patients undergoing PCI were randomized to POC rapid CYP2C19 *2, *3, and *17 genotyping versus no genotyping. At 12 months post-PCI, TaqMan genotyping determined 99.1% (2,364/2,385) concordance with the POC results, with 90.7-98.8% sensitivity and 99.2-99.6% specificity. In conclusion, non-laboratory personnel can be successfully trained for on-site instrument operation and POC rapid genotyping with analytical accuracy and precision across multiple international centers, thereby supporting POC genotyping in patient-care settings, such as the cardiac catheterization laboratory.Clinical Trial Registration: https://www.clinicalTrials.gov (Identifier: NCT01742117).

Contemporary trends in the management of aortic stenosis in the USA.

AIMS: To assess the contemporary trends in aortic stenosis (AS) interventions in the USA before and after the introduction of transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: We utilized the National-Inpatient-Sample to assess temporal trends in the incidence, cost, and outcomes of AS interventions between 1 January 2003 and 31 December 2016. During the study's period, AS interventions increased from 96 to 137 per 100 000 individuals > 60 years old, P < 0.001. In-hospital expenditure on AS interventions increased from $2.28 billion in 2003 to $4.33 in 2016 P < 0.001. Among patients who underwent aortic valve replacement, the proportion of TAVI increased from 11.9% in 2012 to 43.2% in 2016 (P < 0.001). Males and Hispanics had lower proportions of TAVI compared with females and White patients. Adjusted in-hospital mortality of isolated SAVR decreased from 5.4% in 2003 to 3.3% in 2016 (P < 0.001), whereas adjusted in-hospital mortality of TAVI decreased from 4.7% in 2012 to 2.2% in 2016, P < 0.001. The incidence of new dialysis, permanent pacemaker implantation, and blood transfusion decreased after both TAVI and SAVR between 2012 and 2016. However, the rate of post-operative stroke did not significantly decrease. Length of stay and cost of hospitalization decreased after both SAVR and TAVI, although the later remained higher with TAVI. Rates of non-home discharge decreased over time after TAVI but remained stable after isolated SAVR. CONCLUSION: This nationwide survey documents the increasing incidence of AS interventions, the rising cost of modern AS care, and the paradigm shift in aortic valve replacement practice in the USA.

Technical success and long-term outcomes after anomalous right coronary artery stenting with cardiac computed tomography angiography correlation.

INTRODUCTION: Anomalous origin of coronary arteries has been observed in about 0.35-2.10% of the population. Patients with anomalous right coronary artery (ARCA) may present with significant symptoms, arrhythmias or ACS, and at times sudden death. Traditionally, surgical correction has been the recommended treatment. However, these may be technically challenging, and bypass grafting for such anomalies has the potential for graft failure because of competitive flow. We sought to determine the intermediate and long-term outcomes of drug-eluting stent placement for patients with symptomatic ARCA. We also looked at angiographic findings suggestive of interarterial course as confirmed by subsequent computed tomography (CT) findings. METHODS: Between January 2005 and December 2012, we enrolled 11 patients for elective percutaneous coronary intervention (PCI) of ARCA in a single center, prospective, nonrandomized fashion. Patients were followed up in clinic at 1 week, 3 months, 6 months, and 1 year, and then annually or more frequently if needed. All patients underwent a cardiac CT, as well as functional stress testing when needed to assess for recurrence of disease. RESULTS: All 11 of our patients, who presented with significant symptomatic stenosis with an ARCA, were successfully treated with PCI. Mean follow-up duration was 8.5 years. The only two deaths during follow-up were related to noncardiac causes (sepsis), with a mortality rate of 18.2%. Two patients had a positive functional study and on subsequent coronary angiography, one of them had significant in-stent restenosis (target lesion revascularization of 9.1%) and one distal to the stent (target vessel revascularization 9.1%). We found the observation of a "slit-like lesion" on angiography to have a sensitivity of 100% and specificity of 86% for the diagnosis of interarterial course of the anomalous vessel seen on subsequent CT. CONCLUSIONS: Our study results suggest that PCI of ARCA is an effective and low-risk alternative to surgical correction, with good procedural success and long-term outcomes. It can provide symptomatic relief in such patients and may reduce the risk of sudden death in younger patients, without the inherent risks associated with surgical repair.

Pulmonary embolism response team implementation improves awareness and education among the house staff and faculty.

A subset of high-risk pulmonary embolism (PE) patients requires advanced therapy beyond anticoagulation. Significant variation in delivery of care has led institutions to standardize their approach by developing Pulmonary Embolism Response Team (PERT). We sought to assess the impact of PERT implementation on house staff and faculty education. After implementation of PERT, we employed a targeted educational intervention aimed to improve PERT awareness, familiarity with treatment options, role of echocardiogram and Doppler ultrasound, and knowledge of acute PE risk stratification tools. We conducted an anonymous survey among the house staff and faculty before and after intervention to assess the impact of PERT implementation on educational objectives among clinicians. Initial and follow up samples included 115 and 109 responses. The samples were well represented across the subspecialties and all levels of training, as well as junior and senior faculty. Following the educational campaign, awareness of the program increased (72.2-92.6%, p < 0.01). Proportion of clinicians with reported comfort level of managing PE increased (82.4-90.8%, p = 0.07). Proportion of clinicians with self-reported comfort with explaining all available treatment modalities to patients increased (49.1-67.9%, p = 0.005). Proportions of responders who correctly identified the role of echocardiography in risk stratification of patients with known PE increased (73.9-84.4%, p = 0.07). Accurate clinical risk stratification of acute PE increased (60.2-73.8%, p = 0.03). The implementation of a targeted educational program at a tertiary care center increased awareness of PERT among house staff and faculty and improved physician's accuracy of clinical risk stratification and comfort level with management of acute PE.

Effect of Genotype-Guided Oral P2Y12 Inhibitor Selection vs Conventional Clopidogrel Therapy on Ischemic Outcomes After Percutaneous Coronary Intervention: The TAILOR-PCI Randomized Clinical Trial.

Importance: After percutaneous coronary intervention (PCI), patients with CYP2C19*2 or *3 loss-of-function (LOF) variants treated with clopidogrel have increased risk of ischemic events. Whether genotype-guided selection of oral P2Y12 inhibitor therapy improves ischemic outcomes is unknown. Objective: To determine the effect of a genotype-guided oral P2Y12 inhibitor strategy on ischemic outcomes in CYP2C19 LOF carriers after PCI. Design, Setting, and Participants: Open-label randomized clinical trial of 5302 patients undergoing PCI for acute coronary syndromes (ACS) or stable coronary artery disease (CAD). Patients were enrolled at 40 centers in the US, Canada, South Korea, and Mexico from May 2013 through October 2018; final date of follow-up was October 2019. Interventions: Patients randomized to the genotype-guided group (n = 2652) underwent point-of-care genotyping. CYP2C19 LOF carriers were prescribed ticagrelor and noncarriers clopidogrel. Patients randomized to the conventional group (n = 2650) were prescribed clopidogrel and underwent genotyping after 12 months. Main Outcomes and Measures: The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia at 12 months. A secondary end point was major or minor bleeding at 12 months. The primary analysis was in patients with CYP2C19 LOF variants, and secondary analysis included all randomized patients. The trial had 85% power to detect a minimum hazard ratio of 0.50. Results: Among 5302 patients randomized (median age, 62 years; 25% women), 82% had ACS and 18% had stable CAD; 94% completed the trial. Of 1849 with CYP2C19 LOF variants, 764 of 903 (85%) assigned to genotype-guided therapy received ticagrelor, and 932 of 946 (99%) assigned to conventional therapy received clopidogrel. The primary end point occurred in 35 of 903 CYP2C19 LOF carriers (4.0%) in the genotype-guided therapy group and 54 of 946 (5.9%) in the conventional therapy group at 12 months (hazard ratio [HR], 0.66 [95% CI, 0.43-1.02]; P = .06). None of the 11 prespecified secondary end points showed significant differences, including major or minor bleeding in CYP2C19 LOF carriers in the genotype-guided group (1.9%) vs the conventional therapy group (1.6%) at 12 months (HR, 1.22 [95% CI, 0.60-2.51]; P = .58). Among all randomized patients, the primary end point occurred in 113 of 2641 (4.4%) in the genotype-guided group and 135 of 2635 (5.3%) in the conventional group (HR, 0.84 [95% CI, 0.65-1.07]; P = .16). Conclusions and Relevance: Among CYP2C19 LOF carriers with ACS and stable CAD undergoing PCI, genotype-guided selection of an oral P2Y12 inhibitor, compared with conventional clopidogrel therapy without point-of-care genotyping, resulted in no statistically significant difference in a composite end point of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia based on the prespecified analysis plan and the treatment effect that the study was powered to detect at 12 months. Trial Registration: ClinicalTrials.gov Identifier: NCT01742117.

International survey of patients undergoing percutaneous coronary intervention and their attitudes toward pharmacogenetic testing.

OBJECTIVE: To evaluate perceptions toward pharmacogenetic testing of patients undergoing percutaneous coronary intervention (PCI) who are prescribed dual antiplatelet therapy (DAPT) and whether geographical differences in these perceptions exist. PARTICIPANTS AND METHODS: TAILOR-PCI is the largest genotype-based cardiovascular clinical trial randomizing participants to conventional DAPT or prospective genotyping-guided DAPT. Enrolled patients completed surveys before and 6 months after randomization. RESULTS: A total of 1327 patients completed baseline surveys of whom 28, 29, and 43% were from Korea, Canada and the USA, respectively. Most patients (77%) valued identifying pharmacogenetic variants; however, fewer Koreans (44%) as compared with Canadians (91%) and USA (89%) patients identified pharmacogenetics as being important (P<0.001). After adjusting for age, sex, and country, those who were confident in their ability to understand genetic information were significantly more likely to value identifying pharmacogenetic variants (odds ratio: 30.0; 95% confidence interval: 20.5-43.8). Only 21% of Koreans, as opposed to 86 and 77% of patients in Canada and USA, respectively, were confident in their ability to understand genetic information (P<0.001). CONCLUSION: Although genetically mediated clopidogrel resistance is more prevalent amongst Asians, Koreans undergoing PCI identified pharmacogenetic variants as less important to their healthcare, likely related to their lack of confidence in their ability to understand genetic information. To enable successful implementation of pharmacogenetic testing on a global scale, the possibility of international population differences in perceptions should be considered.

Comparison of local versus general anesthesia in patients undergoing transcatheter aortic valve replacement: A meta-analysis.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is typically performed under general anesthesia (GA). However, there is increasing data supporting the safety of performing TAVR under local anesthesia/conscious sedation (LA). We performed a meta-analysis to gain better understanding of the safety and efficacy of LA versus GA in patients with severe aortic stenosis undergoing TAVR. METHODS AND RESULTS: We comprehensively searched EMBASE, PubMed, and Web of Science. Effect sizes were summarized using risk ratios (RRs) difference of the mean (DM), and 95% CIs (confidence intervals) for dichotomous and continuous variables respectively. Twenty-six studies and 10,572 patients were included in the meta-analysis. The use of LA for TAVR was associated with lower overall 30-day mortality (RR, 0.73; 95% CI, 0.57-0.93; P = 0.01), use of inotropic/vasopressor drugs (RR, 0.45; 95% CI, 0.28-0.72; P < 0.001), hospital length of stay (LOS) (DM, -2.09; 95% CI, -3.02 to -1.16; P < 0.001), intensive care unit LOS (DM, -0.18; 95% CI, -0.31 to -0.04; P = 0.01), procedure time (DM, -25.02; 95% CI, -32.70 to -17.35; P < 0.001); and fluoroscopy time (DM, -1.63; 95% CI, -3.02 to -0.24; P = 0.02). No differences were observed between LA and GA for stroke, cardiovascular mortality, myocardial infarction, permanent pacemaker implantation, acute kidney injury, paravalvular leak, vascular complications, major bleeding, procedural success, conduction abnormalities, and annular rupture. CONCLUSION: Our meta-analysis suggests that use of LA for TAVR is associated with a lower 30-day mortality, shorter procedure time, fluoroscopy time, ICU LOS, hospital length of stay, and reduced need for inotropic support.

Balloon Valvuloplasty to Predict X-ray Projection Angles that are Perpendicular to Cardiovascular Structures: A TAVI Patient Feasibility Study.

OBJECTIVES: The purpose of this work is to describe methods to measure the 3D angular orientation of cardiovascular structures based on a planar image of a valvuloplasty balloon. These methods facilitate X-ray beam alignment with respect to the anatomy of interest. BACKGROUND: X-ray beam projections which are perpendicular to the long axis of cardiovascular structures are required to support interventional procedures, including transcatheter aortic valve implant (TAVI). METHODS: During the TAVI procedure, the 3D angular orientation of the LVOT of 10 patients was measured from a single planar image of an aortic valvuloplasty balloon and the continuous range of X-ray projection angles which are aligned with the aortic valve plane were calculated (research method). Misalignment of the X-ray beam and TAVI valve frame was measured from images of the deployed valve. The accuracy of the research method was compared to clinical standard method to determine appropriate X-ray projection angles, which utilized CT and aortography. RESULTS: Using the clinical standard method, the median misalignment of the X-ray beam and TAVI valve frame was 8.6° (range 2.6° to 21°). Misalignment was reduced to 2.5° (range 0° to 10°) using the research method. CONCLUSIONS: The 3D angular orientation of cardiovascular structures can be measured accurately from a single X-ray projection image of a known cardiovascular device contained within the anatomy of interest. For TAVI procedures, improved X-ray beam alignment may help facilitate procedural success. © 2016 Wiley Periodicals, Inc.

Assisted care as a baseline patient risk characteristic affecting the outcome of transcatheter aortic valve insertion.

BACKGROUND: Objective measures of frailty have not been well defined as risk factors for a poor outcome after transcatheter aortic valve insertion. We hypothesized that assisted care as a baseline patient characteristic was a simple objective measure of frailty. We reviewed our experience to assess for an association between assisted care and outcome of operation. METHODS: We retrospectively reviewed the records of 597 patients operated with transcatheter aortic valve insertion from November 2008 through July 2015. The study cohort included patients with a dichotomous baseline characteristic of receiving assisted care (AC group, n = 60, 10.1%) or not receiving assisted care (NC group, n = 537, 89.9%). The endpoints of the study were operative stroke/death and 1-year survival. RESULTS: The age of the patients was 80.6 ± 9.0 years, male sex was present in 349 (58.5%), and STS predicted risk of mortality was 9.2 ± 6.2%. Alternate access was used in 26 (43.3%) patients in the AC care group and in 220 (41.0%) in the NC group (P = 0.724). Operative stroke/death occurred in 4 (6.7%) patients in the AC group and in 25 (4.7%) in the NC group (P = 0.492). Mortality at 1 year in the AC group was 14.8 ± 5.2% and in the NC group was 12.9 ± 1.7%; (P = 0. 250). CONCLUSIONS: Assisted care as a baseline patient characteristic does not result in increased operative stroke/death or 1-year mortality in patients following transcatheter aortic valve insertion. Assisted care should not by itself preclude operation. © 2016 Wiley Periodicals, Inc.

Experience and complications associated with use of guide extension catheters in percutaneous coronary intervention.

OBJECTIVES: To investigate the utility and safety of the GuideLiner "mother-and-child" catheter system during transradial and transfemoral percutaneous coronary intervention (PCI). BACKGROUND: In patients with complex coronary anatomy, stent delivery can be challenging and result in procedural failure and complications. The GuideLiner is a coaxial guide extension system designed to enable deep vessel engagement and facilitate device delivery. The purpose of this study was to evaluate procedural success and safety in a series of GuideLiner-facilitated PCI. METHODS: Single center retrospective study of PCI utilizing the GuideLiner catheter between February 2010 and October 2014. Patients who underwent PCI without GuideLiner use during the same time period were used as controls for comparison. RESULTS: A total of 363 cases of GuideLiner-facilitated PCI were identified from 6,088 unique PCI procedures performed during this same time period. Patients in the GuideLiner group were older (mean age 71.5 vs. 67.8, P < 0.001) and had more multivessel disease (72% vs. 63%, P = 0.001) compared with controls. Type C lesions were present in 78% of GuideLiner cases. Procedural success resulting in successful device delivery with the GuideLiner catheter was 80.2%. Stent deformation associated with GuideLiner use occurred in 2.2% (8/363), with the incidence of this complication decreasing over device iterations. Coronary dissection attributed to GuideLiner occurred in 3.3% (12/363) and became less frequent over the study period. CONCLUSIONS: In this consecutive series of GuideLiner supported PCI, the guide extension system enabled procedural success in the majority. A decline in device-associated complications over time may be attributed to operator learning curve, patient selection, and improvement in catheter design. © 2015 Wiley Periodicals, Inc.

Transaortic valve implantation via occluded saphenous vein grafts--a novel access route for transcatheter aortic valve delivery.

Transaortic valve implantation via direct aortic puncture has been shown to be useful alternative to more traditional access routes. In patients with previously placed ascending aorta saphenous vein grafts, access to the aortic valve may be limited. We therefore sought to detail the utility of a new approach for accessing the ascending aorta during transcatheter aortic valve implantation via the hood of previously placed saphenous vein grafts.

Beyond the learning curve: transapical versus transfemoral transcatheter aortic valve replacement in the treatment of severe aortic valve stenosis.

BACKGROUND: Most studies comparing transapical and transfemoral transcatheter aortic valve replacement include the center's early operative experience, which may negatively impact the outcomes. This study reports our experience beyond the learning curve with transapical and transfemoral transcatheter aortic valve replacement. METHODS: A total of 303 patients underwent transcatheter aortic valve replacement from November 2008 through August 2013. There were 153 patients (50.5%) who received transfemoral valve replacement, 130 (42.9%) received transapical valve replacement, and 20 (6.6%) received transaortic valve replacement. We retrospectively reviewed the outcomes of the most recent 100 consecutive patients each from the transfemoral and transapical valve replacement groups. RESULTS: The median age was 82 years (range, 54 to 95) and 110 patients (55%) were male; STS predicted risk of mortality was 8.1% (0.7 to 27.8) and was similar between groups (p = 0.256). Operative complications occurred in 49 patients (49%) in the transapical replacement group and in 43 (43%) in the transfemoral group (p = 0.478). Vascular complications occurred only in the transfemoral group and included nine patients (9%; p = 0.003). Paravalvular regurgitation at discharge of grade mild-moderate occurred in 23 patients (24.2%) in the transapical group in comparison to 40 (43.5%) in the transfemoral group (p = 0.006). Operative mortality occurred in two patients (2%) in the transapical group and in five (5%) in the transfemoral group (p = 0.445). CONCLUSIONS: Transapical transcatheter aortic valve replacement is associated with less prevalence of vascular complications and mild-moderate paravalvular regurgitation in comparison to the transfemoral approach. Further study is necessary to determine if the transapical technique is the preferred option. doi: 10.1111/jocs.12323 (J Card Surg 2014;29:303-307).

Axillary artery conduit formation for arterial access during transapical transcatheter aortic valve replacement.

BACKGROUND: Transapical transcatheter valve replacement is a relatively new technique for select patients with aortic valve stenosis, most of whom have severe peripheral vascular disease. We report our experience with the use of a right axillary artery conduit for arterial access during transapical valve replacement. METHODS: We reviewed the records of 129 patients who underwent transapical transcatheter aortic valve replacement between November 2009 and August 2013. The study group included 26 (20.2%) patients who received a right axillary artery conduit for arterial access. Median age of the patients was 84 years (63 to 90), sex was female in seven (26.9%), and Society of Thoracic Surgeons predicted risk of mortality was 8.7% (1.8 to 21.2). RESULTS: Axillary artery conduit use was significantly more common during the first half of our operative experience (24/65 patients, 36.9%) in comparison to the second half (2/64 patients, 3.1%; p < 0.0001). Inadequate iliofemoral artery diameter for cardiopulmonary bypass support was present in six patients (23.1%) who received a conduit. All patients underwent successful placement of the axillary artery conduit and subsequent conduit access for catheter-based procedures. Cardiopulmonary bypass support was provided to five (19.2%) patients. Operative mortality occurred in three (11.5%) patients and complications in 12 (46.2%), neither of which were related to the axillary artery conduit. CONCLUSIONS: Creation of an axillary artery conduit provides a safe arterial access platform for transapical transcatheter aortic valve replacement.

Diastolic dysfunction and clinical outcomes after transcatheter or surgical aortic valve replacement in patients with atypical aortic valve stenosis.

BACKGROUND: Diastolic dysfunction is a predictor of poor outcomes in many cardiovascular conditions. At present, it is unclear whether diastolic dysfunction predicts adverse outcomes in patients with atypical aortic stenosis who undergo aortic valve replacement (AVR). METHODS: Five hundred and twenty-three patients who underwent transcatheter AVR (TAVR) (n = 303) and surgical AVR (SAVR) (n = 220) at a single institution were included in our analysis. Baseline left and right heart invasive hemodynamics were assessed. Baseline transthoracic echocardiograms were reviewed to determine aortic stenosis subtype and parameters of diastolic dysfunction. Aortic stenosis subtype was categorized as typical (normal flow, high-gradient) aortic stenosis, classical, low-flow, low-gradient (cLFLG) aortic stenosis, and paradoxical, low-flow, low-gradient (pLFLG) aortic stenosis. Cox proportional hazard models were utilized to examine the relation between invasive hemodynamic or echocardiographic variables of diastolic dysfunction, aortic stenosis subtype, and all-cause mortality. Propensity-score analysis was performed to study the relation between aortic stenosis subtype and the composite outcome [death/cerebrovascular accident (CVA)]. RESULTS: The median STS risk was 5.3 and 2.5% for TAVR and SAVR patients, respectively. Relative to patients with typical aortic stenosis, patients with atypical (cLFLG and pLFLG) aortic stenosis displayed a significantly higher prevalence of diastolic dysfunction (LVEDP ≥ 20mmHg, PCWP ≥ 20mmHg, echo grade II or III diastolic dysfunction, and echo-PCWP ≥ 20mmHg) and, independently of AVR treatment modality, had a significantly increased risk of death. In propensity-score analysis, patients with atypical aortic stenosis had higher rates of death/CVA than typical aortic stenosis patients, independently of diastolic dysfunction and AVR treatment modality. CONCLUSION: We demonstrate the novel observation that compared with patients with typical aortic stenosis, patients with atypical aortic stenosis have a higher burden of diastolic dysfunction. We corroborate the worse outcomes previously reported in atypical versus typical aortic stenosis and demonstrate, for the first time, that this observation is independent of AVR treatment modality. Furthermore, the presence of diastolic dysfunction does not independently predict outcome in atypical aortic stenosis regardless of treatment type, suggesting that other factors are responsible for adverse clinical outcomes in this higher risk cohort.

Transcatheter aortic valve insertion catastrophe in inoperable patients: should aortic valve replacement be denied?

This paper reports the outcomes of patients initially deemed inoperable for standard aortic valve replacement who received transcatheter aortic valve insertion. Each patient experienced a transcatheter valve insertion complication and was then subsequently reconsidered for urgent standard valve replacement. We review the outcomes of these inoperable patients and discuss recommendations for managing this complication.

Transcatheter aortic valve replacement in patients with cirrhosis.

BACKGROUND: Patients with cirrhosis who undergo cardiac operation with extracorporeal circulation are at high risk for operative morbidity and mortality. Transcatheter aortic valve replacement (TAVR) can obviate the need for cardiopulmonary bypass and may reduce operative morbidity in comparison to standard aortic valve replacement (SAVR) in select patients. METHODS: Review of 18 patients with aortic valve stenosis and cirrhosis treated with TAVR (n=6) or SAVR (n=12). Patient age was 71 years (58 to 83) and STS Predicted Risk of Mortality was 3.2% (0.7 to 12.3). There were 15 males (83%). Child-Turcotte-Pugh stage was A in 10 patients (56%), B in four (22%), and C in two (11%); the median MELD score was nine (7 to 14). RESULTS: TAVR was successful in all patients without the need for mechanical or cardiopulmonary bypass support. Blood transfusion occurred in four patients (67%) in the TAVR group and in the entire SAVR group. No deaths occurred in the TAVR group, and two (17%) occurred in the SAVR group. Operative complications occurred in two patients (33%) in TAVR group and in eight (67%) in the SAVR group. Hospital stay was five days (3 to 10) in the TAVR group and six (3 to 38) in the SAVR group. All TAVR patients were alive at last follow-up of 219 days (29 to 723), while only five were alive in the SAVR group at 228 days (36 to 719). CONCLUSIONS: Our initial experience with TAVR in patients with cirrhosis is encouraging. The technique may be a viable alternative to SAVR in this high-risk subset of patients.

Early transcatheter aortic valve thrombosis.

Early valve thrombosis is uncommon after pericardial aortic valve replacement. In this report, we describe such a complication after transcatheter aortic valve insertion.

Vascular access site injury after transfemoral transcatheter aortic valve insertion.

BACKGROUND: Vascular complications associated with transfemoral transcatheter aortic valve insertion (TAVI) are a frequent untoward consequence of arterial sheath insertion. We report the prevalence of anatomic arterial injury with open artery access TAVI. METHODS: This review consisted of 53 consecutive patients who received transfemoral Sapien 23 or 26 mm TAVI via the 22- or 24-French sheath through open artery access from November 2008. The median age of the patients was 83 years (range, 59 to 94), and there were 31 males (58%). All arteries were examined to determine the optimal point of access and then explored after removal of the sheath to document injury. RESULTS: The accessed artery had a minimal lumen diameter of 8.9 mm (7.2 to 14.7) and a sheath-to-artery ratio of 1.0 (0.6 to 1.2). The point of access was the common femoral artery in 33 patients (62%) and the external iliac artery in 20 (38%). Exploration of the artery demonstrated localized arterial injury in 22 patients (42%). Female gender was predictive of injury (p = 0.03), but arterial access site location, presence of arterial access calcification, sheath-to-artery ratio, and sheath size were not. Techniques of artery repair included primary closure in 34 patients (64%), pericardial patch angioplasty in 15 (28%), and graft interposition in 4 (8%). There was one minor groin wound complication. CONCLUSIONS: Open artery access allows for direct examination and optimal access site choice of the vessel during transfemoral TAVI. Localized arterial injury was commonly encountered after 22- and 24-French sheath insertion, but the associated artery repair complication rate was low.

Diazoxide Choline Extended-Release Tablet in People With Prader-Willi Syndrome: A Double-Blind, Placebo-Controlled Trial.

CONTEXT: Prader-Willi syndrome (PWS) is a rare neurobehavioral-metabolic disease caused by the lack of paternally expressed genes in the chromosome 15q11-q13 region, characterized by hypotonia, neurocognitive problems, behavioral difficulties, endocrinopathies, and hyperphagia resulting in severe obesity if not controlled. OBJECTIVE: The primary end point was change from baseline in hyperphagia using the Hyperphagia Questionnaire for Clinical Trials (HQ-CT). Other end points included Global Impression Scores, and changes in body composition, behaviors, and hormones. METHODS: In DESTINY PWS, a 13-week, randomized, double-blind, placebo-controlled, phase 3 trial, 127 participants with PWS aged 4 years and older with hyperphagia were randomly assigned 2:1 to diazoxide choline extended-release tablet (DCCR) or placebo. RESULTS: DCCR did not significantly improve hyperphagia (HQ-CT least-square mean (LSmean) [SE] -5.94 [0.879] vs -4.27 [1.145]; P = .198), but did so in participants with severe hyperphagia (LSmean [SE] -9.67 [1.429] vs -4.26 [1.896]; P = .012). Two of 3 secondary end points were improved (Clinical Global Impression of Improvement [CGI-I]; P = .029; fat mass; P = .023). In an analysis of results generated pre-COVID, the primary (HQ-CT; P = .037) and secondary end points were all improved (CGI-I; P = .015; Caregiver Global Impression of Change; P = .031; fat mass; P = .003). In general, DCCR was well tolerated with 83.3% in the DCCR group experiencing a treatment-emergent adverse event and 73.8% in the placebo group (not significant). CONCLUSION: DCCR did not significantly improve hyperphagia in the primary analysis but did in participants with severe baseline hyperphagia and in the pre-COVID analysis. DCCR treatment was associated with significant improvements in body composition and clinician-reported outcomes.

Genetic-Guided Oral P2Y12 Inhibitor Selection and Cumulative Ischemic Events After Percutaneous Coronary Intervention.

BACKGROUND: Genetic-guided P2Y12 inhibitor selection has been proposed to reduce ischemic events by identifying CYP2C19 loss-of-function (LOF) carriers at increased risk with clopidogrel treatment after percutaneous coronary intervention (PCI). A prespecified analysis of TAILOR-PCI (Tailored Antiplatelet Therapy Following PCI) evaluated the effect of genetic-guided P2Y12 inhibitor therapy on cumulative ischemic and bleeding events. OBJECTIVES: Here, the authors detail a prespecified analysis of cumulative endpoints. The primary endpoint was cumulative incidence rate of ischemic events at 12 months. Cumulative incidence of major and minor bleeding was a secondary endpoint. Cox proportional hazards models as adapted by Wei, Lin, and Weissfeld were used to estimate the effect of this strategy on all observed events. METHODS: The TAILOR-PCI trial was a prospective trial including 5,302 post-PCI patients with acute and stable coronary artery disease (CAD) who were randomized to genetic-guided P2Y12 inhibitor or conventional clopidogrel therapy. In the genetic-guided group, LOF carriers were prescribed ticagrelor, whereas noncarriers received clopidogrel. TAILOR-PCI's primary analysis was time to first event in LOF carriers. RESULTS: Among 5,276 patients (median age 62 years; 25% women; 82% acute CAD; 18% stable CAD), 1,849 were LOF carriers (903 genetic-guided; 946 conventional therapy). The cumulative primary endpoint was significantly reduced in the genetic-guided group compared with the conventional therapy (HR: 0.61; 95% CI: 0.41-0.89; P = 0.011) with no significant difference in cumulative incidence of major or minor bleeding (HR: 1.36; 95% CI: 0.67-2.76; P = 0.39). CONCLUSIONS: Among CYP2C19 LOF carriers undergoing PCI, a genetic-guided strategy resulted in a statistically significant reduction in cumulative ischemic events without a significant difference in bleeding. (Tailored Antiplatelet Therapy Following PCI [TAILOR-PCI]; NCT01742117).