Faculty Bibliography

Background Previous trials have shown that among high-risk patients with aortic stenosis, survival rates are similar with transcatheter aortic-valve replacement (TAVR) and surgical aortic-valve replacement. We evaluated the two procedures in a randomized trial involving intermediate-risk patients. Methods We randomly assigned 2032 intermediate-risk patients with severe aortic stenosis, at 57 centers, to undergo either TAVR or surgical replacement. The primary end point was death from any cause or disabling stroke at 2 years. The primary hypothesis was that TAVR would not be inferior to surgical replacement. Before randomization, patients were entered into one of two cohorts on the basis of clinical and imaging findings; 76.3% of the patients were included in the transfemoral-access cohort and 23.7% in the transthoracic-access cohort. Results The rate of death from any cause or disabling stroke was similar in the TAVR group and the surgery group (P=0.001 for noninferiority). At 2 years, the Kaplan-Meier event rates were 19.3% in the TAVR group and 21.1% in the surgery group (hazard ratio in the TAVR group, 0.89; 95% confidence interval [CI], 0.73 to 1.09; P=0.25). In the transfemoral-access cohort, TAVR resulted in a lower rate of death or disabling stroke than surgery (hazard ratio, 0.79; 95% CI, 0.62 to 1.00; P=0.05), whereas in the transthoracic-access cohort, outcomes were similar in the two groups. TAVR resulted in larger aortic-valve areas than did surgery and also resulted in lower rates of acute kidney injury, severe bleeding, and new-onset atrial fibrillation; surgery resulted in fewer major vascular complications and less paravalvular aortic regurgitation. Conclusions In intermediate-risk patients, TAVR was similar to surgical aortic-valve replacement with respect to the primary end point of death or disabling stroke. (Funded by Edwards Lifesciences; PARTNER 2 ClinicalTrials.gov number, NCT01314313 .).

BACKGROUND: Female sex is associated with poorer outcomes after surgical aortic valve replacement (SAVR). Data on sex-specific differences after transcatheter aortic valve replacement (TAVR) are conflicting. OBJECTIVE: To examine sex-specific differences in patients undergoing TAVR in the PARTNER (Placement of Aortic Transcatheter Valves) trial. DESIGN: Secondary analysis of the randomized and nonrandomized portions of the PARTNER trial. (ClinicalTrials.gov: NCT00530894). SETTING: 25 hospitals in the United States, Canada, and Germany. PATIENTS: High-risk and inoperable patients (1220 women and 1339 men). INTERVENTION: TAVR. MEASUREMENTS: Demographic characteristics, cardiac and noncardiac comorbidities, mortality, stroke, rehospitalization, vascular complications, bleeding complications, and echocardiographic valve parameters. RESULTS: At baseline, women had lower rates of hyperlipidemia, diabetes, smoking, and renal disease but higher Society of Thoracic Surgeons Predicted Risk of Mortality scores (11.9% vs. 11.1%; P < 0.001). After TAVR, women had more vascular complications (17.3% vs. 10.0%; difference, 7.29 percentage points [95% CI, 4.63 to 9.95 percentage points]; P < 0.001) and major bleeding (10.5% vs. 7.7%; difference, 2.8 percentage points [CI, 0.57 to 5.04 percentage points]; P = 0.012) but less frequent moderate and severe paravalvular regurgitation (6.0% vs. 14.3%; difference, -8.3 percentage points [CI, -11.7 to -5.0 percentage points]; P < 0.001). At 30 days, the unadjusted all-cause mortality rate (6.5% vs. 5.9%; difference, 0.6 percentage point [CI, -1.29 to 2.45 percentage points]; P = 0.52) and stroke incidence (3.8% vs. 3.0%; difference, 0.8 percentage point [CI, -0.62 to 2.19 percentage points]; P = 0.28) were similar. At 1 year, all-cause mortality was significantly lower in women than in men (19.0% vs. 25.9%; hazard ratio, 0.72 [CI, 0.61 to 0.85]; P < 0.001). LIMITATION: Secondary analysis that included nonrandomized trial data. CONCLUSION: Despite a higher incidence of vascular and bleeding complications, women having TAVR had lower mortality than men at 1 year. Thus, sex-specific risk in TAVR is the opposite of that in SAVR, for which female sex has been shown to be independently associated with an adverse prognosis. PRIMARY FUNDING SOURCE: Edwards Lifesciences.

OBJECTIVES: Del Nido cardioplegia in adult cardiac surgery has not been studied although it has been in common use as a "single" dose cardioplegia in pediatric heart surgery. We retrospectively assessed the short-term (in-hospital) clinical outcomes of patients undergoing aortic valve replacement (AVR) using del Nido cardioplegia solution, comparing it to conventional multi-dose whole blood cardioplegia. METHODS: We switched our cardioplegia protocol from conventional whole blood cardioplegia exclusively to del Nido solution in May 2011. In 2011, 240 consecutive patients underwent isolated AVR. One hundred and seventy-eight of them were operated on with the use of del Nido cardioplegia (del Nido group) and whole blood cardioplegia (conventional group) was used in the other 62 patients. Isolated AVR was chosen as a cohort because of its relative simplicity and the similarity of surgical techniques among surgeons. Propensity-score matching identified 54 matched pairs for analysis. RESULTS: The retrograde cardioplegia technique was used in 19 cases (35.2%) in the del Nido group and 52 cases (96.3%) in the conventional group (p<0.001). Mean cardiopulmonary bypass time and mean aortic cross-clamp time were significantly shorter in the del Nido group compared to the conventional group: 71 +/- 16 min vs. 84 +/- 28 min (p<0.01), 52 +/- 14 min vs. 60 +/- 16 min (p<0.01), respectively. Postoperative inotropic support was required in 11 patients (20.4 %) in the del Nido group and 13 patients (24.1 %) in the conventional group (p=0.82) with no statistical difference. No patient required a postoperative intra-aortic balloon pump and in-hospital mortality was 0% in both groups. There was no significant difference in postoperative complications between the two groups. CONCLUSIONS: Short-term outcomes in adult cardiac surgery using del Nido solution were acceptable and comparable to conventional multi-dose whole blood cardioplegia. The del Nido cardioplegia technique was associated with shortened cross-clamp times and less frequent utilization of the retrograde cardioplegia delivery technique.

BACKGROUND: This study sought to evaluate the impact of atrial fibrillation (AF) on clinical outcomes in patients undergoing transcatheter aortic valve replacement. METHODS AND RESULTS: Data were evaluated in 1879 patients with baseline and discharge ECGs who underwent transcatheter aortic valve replacement in the Placement of AoRTic TraNscathetER Valve (PARTNER) trial. A total of 1262 patients manifested sinus rhythm (SR) at baseline/SR at discharge, 113 SR baseline/AF discharge, and 470 AF baseline/AF discharge. Patients who converted from SR to AF by discharge had the highest rates of all-cause mortality at 30 days (P<0.0001 across all groups; 14.2% SR/AF versus 2.6% SR/SR; adjusted hazard ratio [HR]=3.41; P=0.0002) and over 2-fold difference at 1 year (P<0.0001 across all groups; 35.7% SR/AF versus 15.8% SR/SR; adjusted HR=2.14; P<0.0001). The presence of AF on baseline or discharge ECG was a predictor of 1-year mortality (adjusted HR=2.14 for SR/AF group and HR=1.88 for AF/AF groups; P<0.0001 for both groups versus SR/SR). For patients discharged in AF, those with lower ventricular response (ie, <90 bpm) experienced less 1-year all-cause mortality (HR=0.74; P=0.04). CONCLUSIONS: After transcatheter aortic valve replacement, the presence of AF at discharge, and particularly, the conversion to AF by discharge and higher ventricular response are associated with increased mortality. These data underscore the deleterious impact of AF, as well as the need for targeted interventions to improve clinical outcomes, in patients undergoing transcatheter aortic valve replacement. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894.

The elderly population is the fastest growing demographic in Western countries. As the population ages, the incidence of age-related comorbidities such as diabetes mellitus, chronic obstructive pulmonary disease, peripheral vascular disease, renal disease, cerebrovascular disease, and cardiovascular disease increases. With cardiovascular disease occurring in approximately one-quarter of the population over the age of 75 years and more than half of all cardiac procedures performed on this age group, the number of potential elderly surgical candidates is increasing. However, data suggest that old age is associated with increased morbidity and mortality following cardiac surgery. Over the past 2 decades, improvements in myocardial protection, extracorporeal circulation, anesthesia, and surgical techniques have significantly reduced the morbidity and mortality associated with cardiac surgery. Although most prospective studies exclude elderly patients, data from large retrospective studies and subgroup analyses suggest that cardiac surgery is a viable option for many elderly patients with cardiovascular disease, with good outcomes observed in reasonable-risk candidates; moreover, there are a growing number of available less-invasive options for them when surgical risk becomes prohibitive. In this article, we discuss the current state of cardiovascular surgery in the elderly as well as emerging technologies on the horizon.

BACKGROUND:Del Nido (DN) cardioplegia, a calcium-free, hyperkalemic solution containing lidocaine and magnesium has been developed to help reduce intracellular calcium influx and the resulting myocyte damage in the immediate postischemic period following cardiac arrest. DN cardioplegia has been used for pediatric cardiac surgery but its use in complex reoperative surgery has not been studied. We specifically report the outcomes of patients undergoing reoperative cardiac surgery after previous coronary artery bypass grafting with a patent internal mammary artery (IMA). METHODS:Patients undergoing reoperative cardiac surgery with prior coronary bypass grafting surgery were studied between 2010 and 2013. Fourteen patients were identified who required continued retrograde cardioplegia administration. In all cases, an initial antegrade dose was given, followed by continuous retrograde administration. Demographics, co-morbidities, intra-operative variables including cardioplegia volumes, post-operative complications, and patient outcomes were collected. RESULTS:The mean age of all patients was 73.3+/-6.7 years, and 93 % were male. Aortic cross clamp time and cardiopulmonary bypass times were 81+/-35 and 151+/-79 mins, respectively. Antegrade, retrograde and total cardioplegia doses were 1101+/-398, 3096+/-3185 and 4367+/-3751 ml, respectively. An average of 0.93+/-0.92 inotropes and 1.50+/-0.76 pressors were used on ICU admission after surgery. ICU and total hospital lengths of stay were 5.5+/-7.4 and 9.6+/-8.0 days, respectively. Complications occurred in two patients (14 %) (pneumonia and prolonged mechanical ventilation) and new arrhythmias occurred in five patients (36 %) (four new-onset atrial fibrillation and one pulseless electrical activity requiring 2 min of chest compression). No perioperative myocardial infarctions were noted based on electrocardiograms and cardiac serum markers. Postoperatively, left ventricular function was preserved in all patients whereas two patients (14 %) had mild decrease in right ventricular function as assessed by echocardiography. No mortality was observed. CONCLUSION/CONCLUSIONS:Del Nido cardioplegia solution provides acceptable myocardial protection for cardiac surgery that requires continuous retrograde cardioplegia administration. DN cardioplegia's administration in a continuous retrograde fashion with a patent IMA is believed to provide adequate myocardial protection while avoiding injuring the IMA through dissection and clamping.

BACKGROUND: When transcatheter aortic valve replacement (TAVR) cannot be carried out through transfemoral access, alternative access TAVR is indicated. The purpose of this study was to explore inhospital and 1-year outcomes of patients undergoing alternative access TAVR through the transapical (TA) or transaortic (TAo) techniques in the United States. METHODS: Clinical records of 4,953 patients undergoing TA (n = 4,085) or TAo (n = 868) TAVR from 2011 to 2014 in The Society of Thoracic Surgeons (STS)/American College of Cardiology Transcatheter Valve Therapy Registry were linked to Centers for Medicare and Medicaid Services hospital claims. Inhospital and 1-year clinical outcomes were stratified by operative risk; and the risk-adjusted association between access route and mortality, stroke, and heart failure repeat hospitalization was explored. RESULTS: Mean age for all patients was 82.8 +/- 6.8 years. The median STS predicted risk of mortality was significantly higher among patients undergoing TAo (8.8 versus 7.4, p < 0.001). When compared with TA, TAo was associated with an increased risk of unadjusted 30-day mortality (10.3% versus 8.8%) and 1-year mortality (30.3% versus 25.6%, p = 0.006). There were no significant differences between TAo and TA for inhospital stroke rate (2.2%), major vascular complications (0.3%), and 1-year heart failure rehospitalizations (15.7%). Examination of high-risk and inoperable subgroups showed that 1-year mortality was significantly higher for TAo patients classified as inoperable (p = 0.012). CONCLUSIONS: Patients undergoing TAo TAVR are older, more likely female, and have significantly higher STS predicted risk of mortality scores than patients operated on by TA access. There were no risk-adjusted differences between TA and TAo access in mortality, stroke, or readmission rates as long as 1 year after TAVR.

BACKGROUND: Echocardiographic calculation of effective orifice area (EOA) after transcatheter aortic valve replacement is integral to the assessment of transcatheter heart valve (THV) function. The aim of this study was to determine the most accurate method for calculating the EOA of the Edwards SAPIEN and SAPIEN XT THVs. METHODS: One hundred intraprocedural transesophageal echocardiograms were analyzed. To calculate the post-transcatheter aortic valve replacement left ventricular outflow tract (LVOT) stroke volume (SV), four diameters were measured using two-dimensional echocardiography: (1) baseline LVOT diameter (LVOTd_PRE), (2) postimplantation LVOT diameter, (3) native aortic annular diameter, and (4) THV in-stent diameter. Four corresponding areas were planimetered by three-dimensional echocardiography. Two LVOT velocity-time integrals (VTI) were measured with the pulsed-wave Doppler sample volume at (1) the proximal (apical) edge of the valve stent or (2) within the valve stent at the level of the THV cusps. LVOT velocity-time integral with the sample volume at the proximal edge of the valve stent was used with the LVOT and aortic annular measurements above, whereas in-stent VTI was paired with the in-stent THV diameter to yield eight different SVs. Right ventricular outflow tract (RVOT) SV was calculated using RVOT diameter and RVOT VTI and was used as the primary comparator. Transaortic VTI was obtained by continuous-wave Doppler, and EOA calculations using each SV measurement were compared with (1) EOA calculated using RVOTSV and (2) planimetered aortic valve area using three-dimensional echocardiography (AVAplanimetry3D). RESULTS: Post-transcatheter aortic valve replacement EOA calculated using LVOTd_PRE was not significantly different from EOA calculated using RVOTSV (1.88 +/- 0.33 vs 1.86 +/- 0.39 cm2, P = .36) or from AVAplanimetry3D (1.85 +/- 0.28, P = .38, n = 34). All other two-dimensional EOA calculations were statistically larger than EOA calculated using RVOTSV. All three-dimensional echocardiography-based EOA calculations were statistically different from AVAplanimetry3D. CONCLUSIONS: The most accurate EOA after implantation of a balloon-expandable THV is calculated using preimplantation LVOT diameter and VTI.