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Background: Significant controversy continues to confound patient selection and referral for revascularization and mitral valve intervention in patients with ischemic cardiomyopathy (ICM). Cardiac magnetic resonance (CMR) enables comprehensive phenotyping with gold-standard tissue characterization and volumetric/functional measures. Therefore, we sought to determine the impact of CMR-enriched phenomapping patients with ICM to identify differential outcomes following surgical revascularization and surgical mitral valve intervention (sMVi)., Methods: Consecutive patients with ICM referred for CMR between 2002 and 2017 were evaluated. Latent class analysis was performed to identify phenotypes enriched by comprehensive CMR assessment. The primary end point was death, heart transplant, or left ventricular assist device implantation. A multivariable Cox survival model was developed to determine the association of phenogroups with overall survival. Subgroup analysis was performed to assess the presence of differential response to post-magnetic resonance imaging procedural interventions., Results: A total of 787 patients were evaluated (63.0±11.2 years, 24.8% women), with 464 primary events. Subsequent surgical revascularization and sMVi occurred in 380 (48.3%) and 157 (19.9%) patients, respectively. Latent class analysis identified 3 distinct clusters of patients, which demonstrated significant differences in overall outcome ( P <0.001). Latent class analysis identified differential survival benefit of revascularization in patients as well as patients who underwent revascularization with sMVi, based on phenogroup classification, with phenogroup 3 deriving the most survival benefit from revascularization and revascularization with sMVi (hazard ratio, 0.61 [0.43-0.88]; P =0.0081)., Conclusions: CMR-enriched unsupervised phenomapping identified distinct phenogroups, which were associated with significant differential survival benefit following surgical revascularization and sMVi in patients with ICM. Phenomapping provides a novel approach for patient selection, which may enable personalized therapeutic decision-making for patients with ICM., Competing Interests: Disclosures Dr W.H. Wilson Tang is a consultant for Sequana Medical, Cardiol Therapeutics, Genomics plc, Zehna Therapeutics, Boston Scientific, WhiteSwell, Inc, Kiniksa Pharmaceuticals, CardiaTec Biosciences, Intellia Therapeutics, and has received honoraria from Springer Nature, Belvoir Media Group, and American Board of Internal Medicine. Dr Deborah Kwon is funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health under 1R01HL170090-01. Dr Kwon also had a research agreement with Circle cvi42. Dr Xiaofeng Wang is funded by the National Institute of General Medical Sciences of the National Institutes of Health under 1R01GM152717.

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Background: The conventional method of implanting balloon-expandable SAPIEN-3 (S3) valve results in a final 70:30 or 80:20 ratio of the valve in the aorta:left ventricular outflow tract with published rates of permanent pacemaker around 10%. We sought to evaluate whether higher implantation of S3 reduces conduction abnormalities including the need for permanent pacemaker., Methods: We included consecutive patients who underwent transfemoral transcatheter aortic valve replacement using S3 between April 2015 and December 2018 and compared outcomes with typical valve deployment strategy to our more contemporary high deployment technique (HDT). We excluded patients with nontransfemoral access or valve-in-valve., Results: Among 1028 patients, HDT was performed in 406 patients (39.5%). Mean implantation depth under the noncoronary cusp was significantly smaller with HDT compared with conventional technique (1.5±1.6 versus 3.2±1.9 mm; P <0.001). Successful implantation was achieved in 100% of the patients in both groups with no cases of conversion to open heart surgery, second valve implantation within the first transcatheter aortic valve replacement, or coronary occlusion during transcatheter aortic valve replacement. One patient (0.2%) had valve embolization with HDT ( P =0.216). Thirty-day permanent pacemaker rates were lower with HDT (5.5% versus 13.1%; P <0.001), as were rates of complete heart block (3.5% versus 11.2%; P <0.001) and new-onset left bundle branch block (5.3% versus 12.2%; P <0.001). There were no differences in mild (16.5% versus 15.9%; P =0.804), or moderate-to-severe aortic regurgitation (1% versus 2.7%; P =0.081) at 1 year. HDT was associated with slightly higher 1-year mean gradients (13.1±6.2 versus 11.8±4.9 mm Hg; P =0.042) and peak gradients (25±11.9 versus 22.5±9 mm Hg; P =0.026). However, Doppler velocity index was similar (0.47±0.15 versus 0.48±0.13; P =0.772)., Conclusions: Our novel technique for balloon-expandable S3 valve positioning consistently achieves higher implantation resulting in substantial reduction in conduction abnormalities and permanent pacemaker requirement after transcatheter aortic valve replacement without compromising procedural safety or valve hemodynamics. Operators should consider this as an important technique to improve patient outcomes.

Background: In contemporary patients with suspected significant mitral stenosis (MS) undergoing rest and treadmill stress echocardiography, we assessed characteristics and factors associated with longer-term survival., Methods: We studied 515 consecutive patients (asymptomatic/atypical symptoms, mean left ventricular ejection fraction 58±2%; 43% male) with suspected at least moderate MS ([1] native mitral valve [MV]: resting mean MV gradient ≥5 mm Hg or area ≤1.5 cm 2 and [2] prosthetic valve: resting mean MV gradient ≥5 mm Hg or effective orifice area ≤2 cm) who underwent rest and treadmill stress echocardiography between 1/2003 and 12/2013. MS was categorized as rheumatic (n=170, 33%), postsurgical (prior mitral repair/replacement, n=245, 48%), and primary nonrheumatic (n=100, 19%). Primary outcome was all-cause mortality., Results: Mean resting MV gradient and right ventricular systolic pressure were 8.5±3 and 39±13 mm Hg. Patients achieved 95±29% age-sex predicted metabolic equivalents; peak-stress MV gradient and right ventricular systolic pressure were 17±7 and 61±14 mm Hg, respectively. At 54 days (median), 224 (44%) underwent invasive mitral procedure. At 6±4 years, 76 (15%) died. On survival analysis, primary nonrheumatic MS (hazard ratio [HR], 4.92), higher Society of Thoracic Surgeons score (HR, 1.92), lower % age-sex predicted metabolic equivalents (HR, 1.22), and higher peak-stress right ventricular systolic pressure (HR, 1.35), was associated with higher mortality, while invasive mitral procedures were associated with improved survival (HR, 0.67; all P<0.01)., Conclusions: In asymptomatic patients (or with atypical symptoms) with significant MS undergoing treadmill stress echocardiography, higher mortality was associated with primary nonrheumatic MS, lower % age-sex predicted metabolic equivalents, and higher peak-stress right ventricular systolic pressure, while invasive MV procedures were associated with survival.

Background: The Society of Thoracic Surgeons (STS) scores are used to screen patients for transcatheter aortic valve replacement (TAVR). The STS scores were also used to risk stratify patients in major TAVR trials. This study evaluates the reclassification of predicted risk of mortality by the currently available online STS score calculator compared with the 2008 STS risk model in patients undergoing TAVR., Methods and Results: All patients who underwent TAVR from 2006 to 2016 were included in the study. The STS scores for all included patients were calculated by applying the 2008 STS risk model and again using the current STS online calculator. Among 1209 patients who underwent TAVR, 30-day mortality was 27 (2.2%). The overall predicted risk of mortality estimated by using the current online STS risk calculator was significantly lower than the 2008 STS risk model (6.3±4.4 vs 7.3±4.9; P<0.001). A total of 235 (19%) patients were reclassified into a lower risk category per the current STS risk model. In a multivariable logistic regression analysis, patients with persistent atrial fibrillation (odds ratio, 1.4; 95% CI, 1.0-1.9; P=0.03), chronic heart failure (odds ratio, 6.0; 95% CI, 3.8-10.1; P<0.001), and New York Heart Association class IV heart failure (odds ratio, 2.4; 95% CI, 1.3-4.4; P=0.007) were more likely to be reclassified into a lower risk category per the current STS risk model., Conclusions: The current STS calculation method produces significantly lower predicted risk of mortality than the 2008 calculator, more pronounced in patients with certain comorbid conditions. These results should be considered while evaluating data from prior studies of TAVR.

Background: Renal dysfunction is intricately linked to aortic stenosis, with over 25% patients presenting for transcatheter aortic valve replacement having chronic kidney disease (CKD). Prevalence and outcomes of patients with CKD, especially those with end-stage renal disease (ESRD), are controversial. We aimed to compare in-hospital outcomes of patients with CKD or ESRD with those patients with no CKD/ESRD., Methods and Results: Data were obtained using the national inpatient sample between the years 2011 and 2014. We used the International Classification of Diseases, Ninth Edition, Clinical Modification procedure codes 350.5 and 350.6 to identify patients undergoing transcatheter aortic valve replacement. Primary outcome of interest was in-hospital mortality. A 2-tailed P value <0.01 was considered to denote statistical significance for all analyses. We identified 42 189 patients who underwent transcatheter aortic valve replacement between the years 2011 and 2014. Of these, 62.1% (n=26 229) had no CKD/ESRD, 33.7% (n=14 252) had CKD, and 4% (n=1708) had ESRD. Patients with CKD or ESRD had greater in-hospital mortality, hospital length of stay, hemorrhage requiring transfusion, and permanent pacemaker implantation ( P <0.001)., Conclusions: Patients with CKD and ESRD have increased in-hospital mortality and periprocedural adverse events with longer hospital length of stay, when compared with those without CKD., (© 2017 American Heart Association, Inc.)

Background: In patients with bicuspid aortic valve and dilated proximal ascending aorta, we sought to assess (1) factors associated with increased longer-term cardiovascular mortality and (2) incremental prognostic use of indexing aortic root to patient height., Methods and Results: We studied 969 consecutive bicuspid aortic valve patients (50±13 years; 87% men) with proximal aorta ≥4 cm, who also had a gated contrast-enhanced thoracic computed tomography or magnetic resonance angiography. A ratio of ascending aortic area/height was calculated on tomography, and ≥10 cm 2 /m was considered abnormal, as previously reported. Society of Thoracic Surgeons score and cardiovascular death were recorded. Greater than or equal to III+ aortic regurgitation and severe aortic stenosis were seen in 37% and 10%, respectively. Society of Thoracic Surgeons score and right ventricular systolic pressure were 2±3 and 15±16 mm Hg, respectively. Abnormal ascending aortic area/height ratio was noted in 33%; 44% underwent ascending aortic surgery at 34 days. At 10.8 years (interquartile range, 9.6-12.3), 82 (9%) died (0.4% in-hospital postoperative mortality). On multivariable Cox survival analysis, ascending aortic area/height ratio (hazard ratio, 2; 95% confidence interval, 1.20-3.35) was associated with cardiovascular death, whereas aortic surgery (hazard ratio, 0.46; confidence interval, 0.26-0.80) was associated with improved survival (both P <0.01). Of the 405 patients with ascending aortic diameter of 4.5 to 5.5 cm, 64% had an abnormal ascending aortic area/height ratio, and 70% deaths occurred in patients with an abnormal ratio., Conclusions: In bicuspid aortic valve patients with dilated proximal ascending aorta, ascending aortic area/height ratio was independently associated with cardiovascular death., (© 2017 American Heart Association, Inc.)

Background: With improved survival of patients undergoing primary bioprosthetic aortic valve replacement (AVR), reoperation to relieve severe prosthetic aortic stenosis (PAS) is increasing. Timing of redo surgery in asymptomatic/minimally symptomatic patients remains controversial. Left ventricular (LV) global longitudinal strain (GLS) is a marker of subclinical LV dysfunction. In asymptomatic/minimally symptomatic patients with severe PAS undergoing redo AVR, we sought to determine whether LV-GLS provides incremental prognostic use., Methods and Results: We studied 191 patients with severe bioprosthetic PAS (63±16 years, 58% men) who underwent redo AVR between 2000 and 2012 (excluding mechanical PAS, severe other valve disease transcatheter AVR, and LV ejection fraction <50%). Society of Thoracic Surgeons score was calculated. Standard echocardiography data were obtained. LV-GLS was measured on 2-, 3-, and 4-chamber views using velocity vector imaging. Severe PAS was defined as aortic valve area <0.8 cm 2 , mean aortic valve gradient ≥40 mm Hg, and dimensionless index <0.25. A composite outcome of death and congestive heart failure admission was recorded. At baseline, mean Society of Thoracic Surgeons score, LV ejection fraction, mean aortic valve gradients, and right ventricular systolic pressure were 7±6, 58±6%, 54±10 mm Hg and 40±14 mm Hg, whereas 50% had >2+ aortic regurgitation. Median LV-GLS was -14.2% (-11.4, -17.1%). At 4.2±3 years, 41 (22%) patients met the composite end point (2.5% deaths and 1% strokes at 30 days postoperatively). On multivariable Cox survival analysis, LV-GLS was independently associated with longer-term composite events (hazard ratio, 1.21; 95% confidence interval, 1.10-1.33), P <0.01. The C statistic for the clinical model (Society of Thoracic Surgeons score, degree of aortic regurgitation, and right ventricular systolic pressure) was 0.64 (95% confidence interval 0.54-0.79), P <0.001. Addition of LV-GLS to the clinical model increased the C statistic significantly to 0.71 (95% confidence interval 0.58-0.81), P <0.001., Conclusions: In asymptomatic/minimally symptomatic patients with severe bioprosthetic PAS undergoing redo AVR, baseline LV-GLS provides incremental prognostic use over established predictors and could potentially aid in surgical timing and risk stratification., (© 2017 American Heart Association, Inc.)

Background: In patients with a dilated proximal ascending aorta and trileaflet aortic valve, we aimed to assess (1) factors independently associated with increased long-term mortality and (2) the incremental prognostic utility of indexing aortic root to patient height., Methods: We studied consecutive patients with a dilated aortic root (≥4 cm) that underwent echocardiography and gated contrast-enhanced thoracic aortic computed tomography or magnetic resonance angiography between 2003 and 2007. A ratio of aortic root area over height was calculated (cm 2 /m) on tomography, and a cutoff of 10 cm 2 /m was chosen as abnormal, on the basis of previous reports. All-cause death was recorded., Results: The cohort comprised 771 patients (63 years [interquartile range, 53-71], 87% men, 85% hypertension, 51% hyperlipidemia, 56% smokers). Inherited aortopathies, moderate to severe aortic regurgitation, and severe aortic stenosis were seen in 7%, 18%, and 2%, whereas 91% and 54% were on β-blockers and angiotensin-converting enzyme inhibitors, respectively. Aortic root area/height ratio was ≥10 cm 2 /m in 24%. The Society of Thoracic Surgeons score and right ventricular systolic pressure were 3.3±3 and 31±7 mm Hg, respectively. At 7.8 years (interquartile range, 6.6-8.9), 280 (36%) patients underwent aortic surgery (76% within 1 year) and 130 (17%) died (1% in-hospital postoperative mortality). A lower proportion of patients in the surgical (versus nonsurgical) group died (13% versus 19%, P<0.01). On multivariable Cox proportional hazard analysis, aortic root area/height ratio (hazard ratio, 4.04; 95% confidence interval [CI], 2.69-6.231) was associated with death, whereas aortic surgery (hazard ratio, 0.47; 95% CI, 0.27-0.81) was associated with improved survival (both P<0.01). For longer-term mortality, the addition of aortic root area/height ratio ≥10 cm 2 /m to a clinical model (Society of Thoracic Surgeons score, inherited aortopathies, hypertension, hyperlipidemia, medications, aortic regurgitation, and right ventricular systolic pressure), increased the c-statistic from 0.57 (95% CI, 0.35-0.77) to 0.65 (95% CI, 0.52-0.73) and net reclassification index from 0.17 (95% CI, 0.02-0.31) to 0.23 (95% CI, 0.04-0.34), both P<0.01. Of the 327 patients with aortic root diameter between 4.5 and 5.5 cm, 44% had an abnormal aortic root area/height ratio, of which 78% died., Conclusions: In patients with dilated aortic root and trileaflet aortic valve, a ratio of aortic root area to height provides independent and improved stratification for prediction of death., (© 2016 American Heart Association, Inc.)

Background: Prior studies of stroke and transient ischemic attack (TIA) after transcatheter aortic valve replacement (TAVR) are limited by reporting and follow-up variability. This is a comprehensive analysis of time-related incidence, risk factors, and outcomes of these events., Methods and Results: From April 2007 to February 2012, 2621 patients, aged 84±7.2 years, underwent transfemoral (TF; 1521) or transapical (TA; 1100) TAVR in the PARTNER trial (Placement of Aortic Transcatheter Valves; as-treated), including the continued access registry. Stroke and TIA were identified by protocol and adjudicated by a Clinical Events Committee. Within 30 days of TAVR, 87 (3.3%) patients experienced a stroke (TF 58 [3.8%]; TA 29 [2.7%]; P=0.09), 85% within 1 week. Instantaneous stroke risk peaked on day 2, then fell to a low prolonged risk of 0.8% by 1 to 2 weeks. Within 30 days, 13 (0.50%) patients experienced a TIA (TF 10 [0.67%]; TA 3 [0.27%]; P>0.17). Stroke and TIA were associated with lower 1-year survival than expected (TF 47% after stroke versus 82%, and 64% after TIA versus 83%; TA 53% after stroke versus 80%, and 64% after TIA versus 83%). Risk factors for early stroke after TA-TAVR included more postdilatations, pure aortic stenosis without regurgitation, and possibly more pacing runs, earlier date of procedure, and no dual antiplatelet therapy; high pre-TAVR aortic peak gradient was a risk factor for stroke early after TF-TAVR., Conclusions: Risk of stroke or TIA is highest early after TAVR and is associated with increased 1-year mortality. Modifications of TAVR, emboli-prevention devices, and better intraprocedural pharmacological protection may mitigate this risk., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894., (© 2016 American Heart Association, Inc.)

Background: In asymptomatic patients with severe aortic stenosis and preserved left ventricular ejection fraction, we sought to assess incremental prognostic utility of exercise stress echocardiography., Methods and Results: We studied 533 such patients (age, 66±13 years; 78% men; 31% with coronary artery disease) who underwent exercise stress echocardiography between 2001 and 2012. Clinical, echocardiographic, and exercise variables (metabolic equivalents [METs], % of age-sex-predicted METs and heart rate recovery at first minute post exercise) were recorded. The end point was all-cause mortality. The Society of Thoracic Surgeons score, left ventricular ejection fraction, mean resting aortic valve (AV) gradient, indexed AV area, METs, and heart rate recovery were 2.9±3%, 58±4%, 35±11 mm Hg, 0.47±0.1 cm(2)/m(2), 7.8±3, and 26±12 bpm, respectively. Only 50% achieved >100%, whereas 26% achieved <85% age-sex-predicted METs. There were no major exercise stress echocardiography-related complications. Over 6.9±3 years, 341 (64%) underwent AV replacement (54% isolated), and there were 104 (20%) deaths. On multivariable Cox proportional hazard survival analysis, a higher Society of Thoracic Surgeons score (hazard ratio, 1.21), lower % age-sex-predicted METs (hazard ratio 1.15), and slower heart rate recovery (hazard ratio, 1.22) were associated with higher longer-term mortality, whereas AV replacement (time-dependent covariate, hazard ratio, 0.26) was associated with improved survival. The addition of % age-sex-predicted METs to the Society of Thoracic Surgeons score resulted in significant reclassification of longer-term mortality risk (integrated discrimination index, 0.07 [0.03-0.11; P<0.001)., Conclusions: In asymptomatic patients with severe aortic stenosis and preserved left ventricular ejection fraction undergoing exercise stress echocardiography, a lower % of age-sex-predicted METs and slower heart rate recovery were associated with longer-term mortality, whereas AV replacement was associated with improved survival., (© 2016 American Heart Association, Inc.)

Background: In asymptomatic patients with ≥3+ mitral regurgitation and preserved left ventricular (LV) ejection fraction who underwent mitral valve surgery, we sought to discover whether baseline LV global longitudinal strain (LV-GLS) and brain natriuretic peptide provided incremental prognostic utility., Methods and Results: Four hundred and forty-eight asymptomatic patients (61±12 years and 69% men) with ≥3+ primary mitral regurgitation and preserved left ventricular ejection fraction, who underwent mitral valve surgery (92% repair) at our center between 2005 and 2008, were studied. Baseline clinical and echocardiographic data (including LV-GLS using Velocity Vector Imaging, Siemens, PA) were recorded. The Society of Thoracic Surgeons score was calculated. The primary outcome was death. Mean Society of Thoracic Surgeons score, left ventricular ejection fraction, mitral effective regurgitant orifice, indexed LV end-diastolic volume, and right ventricular systolic pressure were 4±1%, 62±3%, 0.55±0.2 cm(2), 58±13 cc/m(2), and 37±15 mm Hg, respectively. Forty-five percent of patients had flail. Median log-transformed BNP and LV-GLS were 4.04 (absolute brain natriuretic peptide: 60 pg/dL) and -20.7%. At 7.7±2 years, death occurred in 41 patients (9%; 0% at 30 days). On Cox analysis, a higher Society of Thoracic Surgeons score (hazard ratio 1.55), higher baseline right ventricular systolic pressure (hazard ratio 1.11), more abnormal LV-GLS (hazard ratio 1.17), and higher median log-transformed BNP (hazard ratio 2.26) were associated with worse longer-term survival (all P<0.01). Addition of LV-GLS and median log-transformed BNP to a clinical model (Society of Thoracic Surgeons score and baseline right ventricular systolic pressure) provided incremental prognostic utility (χ(2) for longer-term mortality increased from 31-47 to 61; P<0.001)., Conclusions: In asymptomatic patients with significant primary mitral regurgitation and preserved left ventricular ejection fraction who underwent mitral valve surgery, brain natriuretic peptide and LV-GLS provided synergistic risk stratification, independent of established factors., (© 2016 American Heart Association, Inc.)

Two guidelines from the American College of Cardiology (ACC), the American Heart Association (AHA), and collaborating societies address the risk of aortic dissection in patients with bicuspid aortic valves and severe aortic enlargement: the "2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for the Diagnosis and Management of Patients With Thoracic Aortic Disease" (Circulation. 2010;121:e266-e369) and the "2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease" (Circulation. 2014;129:e521-e643). However, the 2 guidelines differ with regard to the recommended threshold of aortic root or ascending aortic dilatation that would justify surgical intervention in patients with bicuspid aortic valves. The ACC and AHA therefore convened a subcommittee representing members of the 2 guideline writing committees to review the evidence, reach consensus, and draft a statement of clarification for both guidelines. This statement of clarification uses the ACC/AHA revised structure for delineating the Class of Recommendation and Level of Evidence to provide recommendations that replace those contained in Section 9.2.2.1 of the thoracic aortic disease guideline and Section 5.1.3 of the valvular heart disease guideline., (© 2015 American College of Cardiology Foundation and American Heart Association, Inc.)

Background: With improved event-free survival of patients undergoing primary bioprosthetic aortic valve replacement (AVR), reoperation to relieve severe prosthetic aortic stenosis (PAS) is increasing. We sought to (1) identify of the characteristics of patients with severe bioprosthetic PAS undergoing redo AVR, and (2) assess the outcomes of these patients, along with factors associated with adverse outcomes., Methods and Results: We studied 276 patients with severe bioprosthetic PAS (64±16 years, 58% men) who underwent redo-AVR between 2000 and 2012 (excluding mechanical PAS, severe other valve disease, and transcatheter AVR). Society of Thoracic Surgeons score was calculated. Severe PAS was defined as AV area <0.8 cm(2), mean AV gradient ≥40 mm Hg, or dimensionless index <0.25. A composite outcome of death and congestive heart failure admission was recorded. Mean Society of Thoracic Surgeons score and mean AV gradients were 8±8 and 53±17 mm Hg, whereas 28% had >II+ aortic regurgitation. Only 39% had an isolated redo AVR, the rest were combination surgeries (coronary bypass and/or aortic surgeries). At 4.2±3 years, 64 (23%) patients met the composite end point (48 deaths and 19 congestive heart failure admissions, 2.5% 30-day deaths). On multivariable Cox survival analysis, higher Society of Thoracic Surgeons score (hazard ratio, 1.35), higher grades of aortic regurgitation (hazard ratio, 1.29), and higher right ventricular systolic pressure (hazard ratio, 1.3) were associated with worse longer-term outcomes (all P<0.01)., Conclusions: At an experienced center, in patients with severe bioprosthetic PAS undergoing redo AVR, the majority undergo combination surgeries but have excellent outcomes., (© 2015 American Heart Association, Inc.)

Background: The higher risk of adverse outcomes after transapical (TA) versus transfemoral (TF) transcatheter aortic valve replacement (TAVR) could be attributable to TA-TAVR being an open surgical procedure or to clinical differences between TA- and TF-TAVR patients. We compared outcomes after neutralizing patient differences using propensity score matching., Methods and Results: From April 2007 to February 2012, 1100 Placement of Aortic Transcatheter Valves (PARTNER)-I patients underwent TA-TAVR and 1521 underwent TF-TAVR with Edwards SAPIEN balloon-expandable bioprostheses. Propensity matching based on 111 preprocedural variables, exclusive of femoral access morphology, identified 501 well-matched patient pairs (46% of possible matches), 95% of whom had peripheral arterial disease. Matched TA-TAVR patients experienced more adverse procedural events, longer length of stay (5 versus 8 days; P<0.0001), and slower recovery (New York Heart Association class I, 31% versus 38% at 30 days, equalizing by 6 months at 51% versus 47%); stroke risk was similar (3.4% versus 3.3% at 30 days and 6.0% versus 6.7% at 3 years); mortality was elevated for the first 6 postprocedural months (19% versus 12%; P=0.01); but aortic regurgitation was less (34% versus 52% mild and 8.9% versus 12% moderate to severe at discharge, P=0.001; 36% versus 50% mild and 10% versus 15% moderate to severe at 6 months, P<0.0001)., Conclusions: The likelihood of adverse periprocedural events and prolonged recovery is greater after TA-TAVR than TF-TAVR in vasculopathic patients after accounting for differences in cardiovascular risk factors, although stroke risk is equivalent and aortic regurgitation is less. As smaller delivery systems permit TF-TAVR in many of these patients, we recommend a TF-first access strategy for TAVR when anatomically feasible., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894., (© 2015 American Heart Association, Inc.)

Background: Tricuspid regurgitation (TR) and right ventricular (RV) dysfunction adversely affect outcomes in patients with heart failure or mitral valve disease, but their impact on outcomes in patients with aortic stenosis treated with transcatheter aortic valve replacement has not been well characterized., Methods and Results: Among 542 patients with symptomatic aortic stenosis treated in the Placement of Aortic Transcatheter Valves (PARTNER) II trial (inoperable cohort) with a Sapien or Sapien XT valve via a transfemoral approach, baseline TR severity, right atrial and RV size and RV function were evaluated by echocardiography according to established guidelines. One-year mortality was 16.9%, 17.2%, 32.6%, and 61.1% for patients with no/trace (n=167), mild (n=205), moderate (n=117), and severe (n=18) TR, respectively (P<0.001). Increasing severity of RV dysfunction as well as right atrial and RV enlargement were also associated with increased mortality (P<0.001). After multivariable adjustment, severe TR (hazard ratio, 3.20; 95% confidence interval, 1.50-6.82; P=0.003) and moderate TR (hazard ratio, 1.60; 95% confidence interval, 1.02-2.52; P=0.042) remained associated with increased mortality as did right atrial and RV enlargement, but not RV dysfunction. There was an interaction between TR and mitral regurgitation severity (P=0.04); the increased hazard of death associated with moderate/severe TR only occurred in those with no/trace/mild mitral regurgitation., Conclusions: In inoperable patients treated with transcatheter aortic valve replacement, moderate or severe TR and right heart enlargement are independently associated with increased 1-year mortality; however, the association between moderate or severe TR and an increased hazard of death was only found in those with minimal mitral regurgitation at baseline. These findings may improve our assessment of anticipated benefit from transcatheter aortic valve replacement and support the need for future studies on TR and the right heart, including whether concomitant treatment of TR in operable but high-risk patients with aortic stenosis is warranted., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01314313., (© 2015 American Heart Association, Inc.)

Background: In patients with severe aortic stenosis, transcatheter aortic valve replacement (TAVR) improves survival when compared with nonsurgical therapy but with higher in-hospital and lifetime costs. Complications associated with TAVR may decrease with greater experience and improved devices, thereby reducing the overall cost of the procedure. Therefore, we sought to estimate the effect of periprocedural complications on in-hospital costs and length of stay of TAVR., Methods and Results: Using detailed cost data from 406 TAVR patients enrolled in the Placement of Aortic Transcatheter Valve (PARTNER) I trial, we developed multivariable models to estimate the incremental cost and length of stay associated with specific periprocedural complications. Attributable costs and length of stay for each complication were calculated by multiplying the independent cost of each event by its frequency in the treatment group. Mean cost for the initial hospitalization was $79 619±40 570 ($50 891 excluding the valve); 49% of patients had ≥1 complication. Seven complications were independently associated with increased hospital costs, with major bleeding, arrhythmia, and death accounting for the largest attributable cost per patient. Renal failure and the need for repeat TAVR, although less frequent, were also associated with substantial incremental and attributable costs. Overall, complications accounted for $12 475 per patient in initial hospital costs and 2.4 days of hospitalization., Conclusions: In the PARTNER trial, periprocedural complications were frequent, costly, and accounted for ≈25% of non-implant-related hospital costs. Avoidance of complications should improve the cost-effectiveness of TAVR for inoperable and high-risk patients, but reductions in the cost of uncomplicated TAVR will also be necessary for optimal efficiency., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT00530894., (© 2014 American Heart Association, Inc.)

Background: The long-term outcomes of transcatheter aortic valve replacement (TAVR) in inoperable patients with severe aortic stenosis remain unknown., Methods and Results: In the Placement of Aortic Transcatheter Valves (PARTNER) study, 358 patients were randomly assigned to TAVR or standard therapy. We report the 3-year outcomes on these patients, and the pooled outcomes for all randomly assigned inoperable patients (n=449) in PARTNER, as well, including the randomized portion of the continued access study (n=91). The 3-year mortality rate in the TAVR and standard therapy groups was 54.1% and 80.9%, respectively (P<0.001; hazard ratio, 0.53; 95% confidence interval, 0.41-0.68; P<0.001). In survivors, there was significant improvement in New York Heart Association functional class sustained at 3 years. The cumulative incidence of strokes at 3-year follow-up was 15.7% in TAVR patients versus 5.5% in patients undergoing standard therapy (hazard ratio, 2.81; 95% confidence interval, 1.26-6.26; P=0.012); however, the composite of death or strokes was significantly lower after TAVR versus standard therapy (57.4% versus 80.9%, P<0.001; hazard ratio, 0.60; 95% confidence interval, 0.46-0.77; P<0.001). Echocardiography showed a sustained increase in aortic valve area and decrease in transvalvular gradient after TAVR. Analysis of the 449 pooled randomly assigned patients (TAVR, n=220; standard therapy, n=229) demonstrated significant improvement in all-cause mortality and functional status during early and 3-year follow-up. The results of the pooled cohort were similar to the results obtained from the pivotal PARTNER trial., Conclusions: TAVR resulted in better survival and functional status in inoperable patients with severe aortic stenosis with durable hemodynamic benefit on long-term follow-up. However, high residual mortality, even in successfully treated TAVR patients, highlights the need for more strategic patient selection., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT00530894., (© 2014 American Heart Association, Inc.)

Background: The objective was to evaluate the effects of aortic annulus size on valve hemodynamics and clinical outcomes in those patients included in the Placement of Aortic Transcatheter Valves (PARTNER) randomized controlled trial cohort A and the nonrandomized continued access cohort., Methods and Results: Patients included the randomized controlled trial (n=574) and nonrandomized continued access (n=1358) cohorts were divided in tertiles according to aortic annulus diameter (small aortic annulus tertile, medium aortic annulus tertile, and large aortic annulus tertile [LAA], respectively) as measured by transthoracic echocardiography. Severe prosthesis-patient mismatch was defined as an effective aortic orifice area of <0.65 cm(2)/m(2). In the randomized controlled trial cohort, patients in the small aortic annulus tertile who underwent transcatheter aortic valve replacement had a lower incidence of severe prosthesis-patient mismatch (19.7% versus 37.5%; P=0.03) and only a trend toward a higher incidence of moderate-to-severe paravalvular leaks compared with surgical aortic valve replacement (5.7% versus 0%; P=0.06). In the LAA tertile, there were no differences in the rate of prosthesis-patient mismatch between groups, and a significant increase in moderate-to-severe paravalvular leaks was associated with transcatheter aortic valve replacement (9% versus 0%; P=0.01). There were no differences in mortality between transcatheter aortic valve replacement and surgical aortic valve replacement. In the nonrandomized continued access cohort, there were no differences in prosthesis-patient mismatch between the small aortic annulus and LAA tertiles, but a higher rate of moderate-to-severe paravalvular leaks was observed in the LAA tertile (5.9% versus 11.5%; P=0.009). Patients in the LAA tertile had a higher mortality rate at 1-year follow-up (P=0.02), and differences persisted in multivariable analysis (P=0.048 for LAA versus medium aortic annulus tertile, P=0.035 for LAA versus small aortic annulus tertile)., Conclusions: Aortic annulus size had a major impact on valve hemodynamics and clinical outcomes after transcatheter aortic valve replacement and surgical aortic valve replacement. This study highlights the importance of considering aortic annulus size in the evaluation of high-risk patients who are candidates for aortic valve replacement., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT00530894., (© 2014 American Heart Association, Inc.)

Objective: To describe recent changes in medication preceding out-of-hospital cardiac arrest (OHCA) where resuscitation was attempted., Methods: OHCA victims were identified by the Swedish Cardiac Arrest Register and linked by means of their unique 10-digit personal identification numbers to the Prescribed Drug Register. We identified new claimed prescriptions during a 6-month period before the OHCA compared with those claimed in the period 12 to 18 months before. The 7-digit Anatomical Therapeutical Chemical codes of individual drugs were used. The study period was November 2007-January 2011., Results: OHCA victims with drugs were (1) older than those who did not claim any drugs in any period (70 ± 16 years vs. 54 ± 22 years, P < 0.001), (2) more often women (34% vs. 20%, P < 0.001), and (3) had more often a presumed cardiac etiology (67% vs. 54%, P < 0.001). The OHCA victims were less likely to have ventricular tachycardia/ventricular fibrillation as the first recorded rhythm (26% vs. 33%, P < 0.001) or to survive 1 month (9% vs. 17%, P < 0.0001). New prescriptions were claimed by 5122 (71%) of 7243 OHCA victims. The most frequently claimed new drugs were paracetamol (acetaminophen) 10.3%, furosemide 7.8%, and omeprazole 7.6%. Of drugs known or supposed to cause QT prolongation, ciprofloxacin was the most frequent (3.4%) altogether; 16% had a new claimed prescription of a drug included in the "qtdrugs.org" lists., Conclusions: Most OHCA victims had new drugs prescribed within 6 months before the event but most often intended for diseases other than cardiac. No claims can be made as to the causality.

Background: Preoperative management of patients with aortic stenosis (AS) who need noncardiac surgery (NCS) remains controversial. We sought to determine the impact of AS on the postoperative outcomes after NCS., Methods and Results: Patients undergoing NCS with moderate AS (valve area: 1.0-1.5 cm(2)) or severe AS (valve area: <1.0 cm(2)) were identified using the surgical and the echocardiographic databases. Using propensity score analysis, we obtained 4 matched control patients without AS for each patient with AS undergoing NCS. The propensity score matching used the 6 revised cardiac risk index criteria, in addition to age and sex. Primary outcome was a composite of 30-day mortality and postoperative myocardial infarction. We matched 634 patients with AS undergoing NCS to 2536 controls. There were 244 patients with severe AS and 390 patients with moderate AS. Thirty-day mortality was 2.1% for AS patients compared with 1.0% in non-AS controls (P=0.036). Postoperative myocardial infarction was more frequent in patients with AS compared with controls (3.0% versus 1.1%; P=0.001). Combined primary outcome was significantly worse for both moderate and severe AS patients compared with respective controls (4.4% versus 1.7%; P=0.002; and 5.7% versus 2.7%; P=0.02, respectively). High-risk surgery, symptomatic severe AS, coexisting mitral regurgitation, and preexisting coronary disease were significant predictors of primary outcome in patients with AS., Conclusion: Presence of AS adversely affects postoperative outcomes among patients undergoing NCS, evidenced by a higher 30-day mortality and postoperative myocardial infarction after NCS.

Background: Improving functional status and quality of life are important goals of treatment for patients with severe aortic stenosis. The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a heart failure health status measure and has been used in studies of patients with aortic stenosis. However, its psychometric properties have not yet been evaluated in these patients., Methods and Results: We analyzed data from 955 patients, enrolled in the PARTNER trial of transcatheter aortic valve replacement, to evaluate the reliability, responsiveness, validity, and prognostic importance of the KCCQ in patients with severe aortic stenosis. The KCCQ was administered at baseline and at 1, 6, and 12 months after randomization to medical therapy, transcatheter aortic valve replacement, or surgical valve replacement. Among clinically stable patients, there were only small changes in the KCCQ domain scores over time (mean differences 0.1-4.2 points), and the intraclass correlation coefficients showed good agreement between paired assessments (0.65-0.76). However, the domain scores of patients who underwent transcatheter aortic valve replacement showed large changes after treatment (mean differences 13-30 points). Construct validity was demonstrated by comparing each domain against a relevant reference measure (Spearman correlations 0.46-0.69). Finally, among 157 patients randomized to medical management, lower KCCQ overall summary scores at baseline were strongly associated with an increased risk of mortality during the following 12 months., Conclusions: The KCCQ is a highly reliable, responsive, and valid measure of symptoms, functional status, and quality of life in patients with severe, symptomatic aortic stenosis.

Background: In patients with aortic stenosis (AS), precise assessment of severity is critical for treatment decisions. Estimation of aortic valve area (AVA) with transthoracic echocardiographic (TTE)-continuity equation (CE) assumes a circular left ventricular outflow tract (LVOT). We evaluated incremental utility of 3D multidetector computed tomography (MDCT) over TTE assessment of AS severity., Methods and Results: We included 51 patients (age, 81±8 years; 61% men; mean gradient, 42 ± 12 mm Hg) with calcific AS who underwent evaluation for treatment options. TTE parameters included systolic LVOT diameter (D) and continuous and pulsed wave (CW and PW) velocity-time integrals (VTI) through the LVOT and mean transaortic gradient. MDCT parameters included systolic LVOT area, ratio of maximal to minimal LVOT diameter (eccentricity index), and aortic planimetry (AVA(p)). TTE-CE AVA [(D(2)×0.786×VTIpw)/VTIcw] and dimensionless index (DI) [VTIpw/VTIcw] were calculated. Corrected AVA was calculated by substituting MDCT LVOT area into CE. The majority (96%) of patients had eccentric LVOT. LVOT area, measured on MDCT, was higher than on TTE (3.84 ± 0.8 cm(2) versus 3.03 ± 0.5 cm(2), P<0.01). TTE-AVA was smaller than AVA(p) and corrected AVA (0.67 ± 0.1cm(2), 0.82 ± 0.3 cm(2), and 0.86 ± 0.3 cm(2), P<0.01). Using TTE measurements alone, 73% of patients had congruence for severe AS (DI ≤0.25 and CE AVA <0.8 cm(2)), which increased to 92% using corrected CE., Conclusions: In patients with suspected severe AS, incorporation of MDCT-LVOT area into CE improves congruence for AS severity.

Background: The modern imaging techniques of transesophageal echocardiography, CT, and MRI are reported to have up to 100% sensitivity in detecting the classic class of aortic dissection; however, anecdotal reports of patient deaths from a missed diagnosis of subtle classes of variants are increasingly being noted., Methods and Results: In a series of 181 consecutive patients who had ascending or aortic arch repairs, 9 patients (5%) had subtle aortic dissection not diagnosed preoperatively. All preoperative studies in patients with missed aortic dissection were reviewed in detail. All 9 patients (2 with Marfan syndrome, 1 with Takayasu's disease) with undiagnosed aortic dissection had undergone >/=3 imaging techniques, with the finding of ascending aortic dilatation (4.7 to 9 cm) in all 9 and significant aortic valve regurgitation in 7. In 6 patients, an eccentric ascending aortic bulge was present but not diagnostic of aortic dissection on aortography. At operation, aortic dissection tears were limited in extent and involved the intima without extensive undermining of the intima or an intimal "flap." Eight had composite valve grafts inserted, and all survived. Of the larger series of 181 patients, 98% (179 of 181) were 30-day survivors., Conclusions: In patients with suspected aortic dissection not proven by modern noninvasive imaging techniques, further study should be performed, including multiple views of the ascending aorta by aortography. If patients have an ascending aneurysm, particularly if eccentric on aortography and associated with aortic valve regurgitation, an urgent surgical repair should be considered, with excellent results expected.

We report the improving surgical results in a consecutive series of 690 patients referred to one of us (E.S.C.) for aortic dissection between December 1956 and September 1989, a substantial portion of whom had dissection as a complication of either previous aortic (n = 113, 16) or previous cardiac (n = 54, 8%) operation. Our initial operation of choice in patients requiring multiple operations in this group of 690 patients was based on the most life-threatening or symptomatic aortic segment involved, which was ascending aorta and/or aortic arch (Asc/Arch) in 301 (44%) patients, descending thoracic aorta (Desc) in 195 (28%) patients, and thoracoabdominal aorta (TaA) in 194 (28%) patients. As detailed below, considerable improvement occurred in the 30-day survival rates over time, particularly for acute dissection: [table; see text] The independent determinants of both early and long-term mortality were identified. Independent determinants of late fatal rupture, reoperation, and neuromuscular dysfunction for distal dissectors were also identified. In our experience, continued aggressive surgical intervention for aortic dissection with modern operative techniques has resulted in markedly improved 30-day operative survival (approaching 95% including those patients with acute dissection) and significant improvement in late results.

The life expectancy of patients with aortic aneurysm is significantly prolonged by graft replacement therapy. Regardless, a significant predictor of late death is complications of either residual aortic aneurysmal disease or the development of additional aortic aneurysm. This paper reviews a personal experience in the treatment of 4170 patients with aneurysmal disease of either dissection or medial degenerative origin, indicating that multiple segment involvement was or became present in 1262 (30%) patients, 463 (67%) of 694 patients with dissection, and 799 (23%) of 3476 patients without dissection. Regardless of etiology, multiple involvement varied with the location of the presenting involved segment, i.e., ascending aorta (38%), ascending and arch (70%), descending thoracic aorta (73%), and abdominal aorta (26%). This study was limited in detail to 811 patients who had ascending and ascending and aortic arch replacement for aneurysm. These patients were divided into 3 subgroups: (1) 524 patients with no distal disease; (2) 135 patients with distal disease treated by subtotal replacement in 82 and total replacement in 53; and (3) 152 patients with distal disease not treated. The 5-year survival rate from the time of first operation, including early death from operation was 75% in group 1, 65% in group 2, and 39% in group 3. The causes of death in group 3 patients were aneurysmal rupture and/or associated disease. It is concluded that initial total aortic study and regular postoperative monitoring with computed tomographic scanning is indicated to detect extensive disease or recurrence of disease and that aggressive replacement is indicated except in patients with associated disease that does not permit operation.