Citations

Introduction: Surgically implanted epicardial left ventricular (eLV) lead is an alternative approach when transvenous LV (tLV) lead implantation in CRT patients has failed. With advancement in surgical technique and free from limitations of cardiac venous anatomy, operators have the freedom to choose the most optimal LV pacing site. Recent literatures noted differential clinical response in tLV-CRT patients with different LV lead locations. However, to the best of the authors’ knowledge, no such analysis has been published for eLV-CRT patients. Hypothesis: We hypothesize that optimal LV lead location in eLV-CRT is similar to tLV-CRT and similar clinical response is expected. Methods: After unsuccessful attempt(s) of tLV-CRT implantation, 44 (Age 63±15, 28M) patients received eLV-CRT from UCSD and Mayo Clinics between 2002 and 2013. Two-view (PA, lateral) chest radiographs were used to determine lead location by blinded independent observers. 9 patients were partially excluded from lead location analysis due to congenital cardiac anomaly or unavailable lateral chest radiograph. eLV lead locations were classified as basal, mid, or apical on the PA view; and anterior, anterolateral, lateral, posterolateral, or posterior on the lateral view. Survival data were collected from the national death and location database. Results: During an average follow up of 65 months, 15 patients have died following eLV-CRT implant. No death was attributed to acute surgical complication to eLV-CRT implantation. Kaplan-Meyer survival estimate showed anterior and apical eLV lead positions had lower survival rate as compared to non-anterior (p<0.01, figure A) and non-apical location (p=0.07, figure B). Conclusion: In this two-center study, apical and anterior eLV lead locations were associated with significantly lower survival rate. The study implies apical and/or anterior locations should be avoided, if possible, during eLV-CRT implantation.

Objective: To evaluate outcomes of acute spontaneous coronary artery dissection (SCAD) managed with percutaneous coronary intervention (PCI) or conservative therapy. Background: SCAD is a non-atherosclerotic acute coronary syndrome that typically affects young otherwise healthy females. Whether SCAD with normal vessel flow at presentation should be managed with PCI or conservative therapy remains unknown. Methods: We performed a retrospective study of patients after a first SCAD episode (n=142). We excluded those treated with fibrinolysis (n=12) or coronary artery bypass grafting (CABG, n=8). We evaluated in-hospital and late outcomes in three SCAD groups: Vessel occlusion at presentation treated with PCI (Occ-PCI, n=30); normal vessel flow treated with PCI (NF-PCI, n=34) and those managed conservatively (CON, n=58). Results: Overall mean age was 42+9 years, 91% were female and 41% presented with STEMI. Outcomes are shown in the table below. In Occ-PCI, technical failure occurred in 8/30 (27%), of whom 5 required emergency CABG with one in-hospital death. Comparing NF-PCI with CON, there were no differences in clinical characteristics. Technical failure occurred in 16/34 (47%) of NF-PCI due to failure to cross with wire/device (8/34) or final loss of flow (8/34). Emergency CABG was required in 5 (15%). In CON, 54/58 had an uneventful in-hospital course. Four (7%) exhibited early dissection progression of whom two received PCI and one CABG. Long-term rates of target vessel revascularization, but not recurrent SCAD, were higher in NF-PCI vs CON (26% vs 9%, p=0.02; 24% vs 14%, p=0.23). Conclusions: PCI for acute SCAD is associated with high rates of technical failure and adverse clinical outcomes. In SCAD with normal vessel flow, conservative management may be preferable, with close early observation due to a hazard of progression of dissection. These findings underscore the importance of tailoring therapy to etiology of coronary obstruction.

Background: Left ventricular (LV) mass regression after aortic valve replacement (AVR) for aortic stenosis (AS) is a favorable effect of LV unloading, but its relationship to improved clinical outcomes is unclear. We examined the effect on clinical outcomes after transcatheter AVR (TAVR) of: 1) amount of LV mass index (LVMi) regression; and 2) persistent severe LV hypertrophy (LVH). Methods: Of 2115 patients with symptomatic AS at high surgical risk receiving TAVR in the PARTNER randomized trial or continued access registry, 462 (55% women) who had severe LVH (LVMi ≥149 g/m 2 men, ≥122 g/m 2 women, by ASE criteria) at baseline (BL) and LVMi measured 6 mo post-TAVR were included in our analysis. The effect of LVMi regression was evaluated by comparing outcomes in patients with greater vs. lesser decrease (dichotomized by median % change) in LVMi between BL and 6 mo, and in those without vs. with persistent severe LVH 6 mo post-TAVR. Cox PH models evaluated rates of all-cause mortality (6-12 mo), rehospitalizations (through 1 yr), and the composite of these two outcomes. Results: LVMi decreased from 173±32 (BL) to 121±25 g/m 2 (6 mo) (p<0.001) in those with greater LVMi regression, and from 164±30 (BL) to 158±34 g/m 2 (6 mo) (p<0.001) in those with lesser LVMi regression. Patients with greater vs. lesser LVMi regression had similar baseline clinical characteristics, a lower rate of rehospitalization (10.5% vs. 19.9%, p=0.006) and lower rate of the composite endpoint of death or rehospitalization (13.2% vs. 21.4%, p=0.02), but a similar rate of death (4.9% vs. 4.8%, p=0.86). Persistent severe LVH at 6 mo post-TAVR was present in 54% (58% of whom were women). Patients without vs. with persistent severe LVH had similar baseline clinical characteristics, a lower rate of rehospitalization (11.9% vs. 18.1%, p=0.053) and lower rate of the composite endpoint of death or rehospitalization (13.3% vs. 20.7%, p=0.03), but a similar rate of death (3.9% vs. 5.7%, p=0.42). Similar results were obtained when including patients with moderate or severe LVH. Conclusions: In high-risk patients with severe AS and severe LVH undergoing TAVR, greater LV mass regression and resolution of initially severe LVH at 6 months are associated with a lower rate of death or repeat hospitalization.

Background: Impact of right ventricular (RV) overload on left ventricular (LV) performance has been demonstrated in Ebstein’s anomaly (EA). We have shown that LV radial strain (RS) in 83 EA patients was significantly less than in controls. We subsequently sought to evaluate LV strain after EA surgery. Methods: Systolic strain, strain rate (SR) and early diastolic strain rate (SRe) were retrospectively performed, using velocity vector imaging, in 24 repaired EA patients (age 35 ±12 years; 67% women) with LV ejection fraction >50%, preoperatively (median 5 days [1-145 days]) and postoperatively within 5 years at sequential follow-up (6 months-3 years). Repair of EA included tricuspid valve repair, valve replacement and bidirectional cavopulmonary anastomosis. A slope of change postoperatively was estimated for each subject using linear regression. A one-sample t-test of the mean slope=0 assessed average change per year. Results: Mean (standard deviation) and median (range) of preoperative LV RS was 36.5 +/- 11.4% and 36.3% (16.8-59.8) respectively. LV strain analyses are summarized in tables 1 and 2. Conclusions: LV RS improved significantly after EA surgery whereas circumferential strain (CS), SR and radial SR did not. This may reflect the change in RV and subsequently LV geometry after resolution of tricuspid regurgitation with EA surgery. Ongoing evaluation with deformational imaging may help to characterize if these changes are compensatory or maladaptive and may determine optimal timing for surgery. In the subgroup with the lowest RS, significant improvement postoperatively was not seen. This may suggest that surgery was performed too late to allow favorable remodeling.

Background: Shock is a highly dreaded complication of type A acute aortic dissection (TAAAD). However, few data exist on its incidence and association with prognosis. Methods: We evaluated 2704 TAAAD patients [mean age 61.4 ± 14.5, (67.6%) male] from the International Registry of Acute Aortic Dissection. Results: Shock was present at arrival in 407 (15.1%) TAAAD patients. These patients demonstrated no difference in age (61.5 ± 15.2 with shock vs. 61.4 ± 14.4 years without; p=0.873), but were more likely to have history of hypertension (83.1% vs. 73.0%; p<0.001), atherosclerosis (36.5% vs. 21.7%, p<0.001) and diabetes (12.3% vs. 7.0%, p=0.001) than patients without shock. They had more surgical management (90.9% vs. 86.0%; p=0.007). In-hospital complications such as hypotension (49.8% vs. 28.6%; p<0.001), coma (11.4% vs. 5.8%; p<0.001), tamponade (33.6% vs. 18.2%; p<0.001) and myocardial ischemia/infarction (19.7% vs. 13.7%; p=0.006) were more common among shock patients. Overall in-hospital mortality (30.2% vs. 23.9%; p=0.007) and mortality by management (surgical: 24.6% vs. 19.1%; p=0.015; medical: 88.9% vs. 53.3%, p<0.001) were higher among shock patients. Independent predictors of in-hospital mortality in shock patients are displayed in Table 1. Among hospital survivors, Kaplan-Meier estimates of follow-up mortality were similar between groups (p=0.609). Conclusions: Shock occurred in 15.1% of patients with TAAAD and was associated with increased in-hospital morbidity and mortality, but not long-term mortality.

Introduction: Point source ablation may be effective in eliminating stable ventricular tachycardia (VT), where actual mapping and ablation are possible. Ablating patients with unstable VT is more complicated and may require aggressive intervention. While small linear lesions have been utilized, the actual utility of longer linear homogenization for eliminating ventricular arrhythmias has not been examined. Methods: Therefore, the results of 86 patients undergoing VT ablation at Mayo Clinic were examined. 42 had underlying ischemic heart disease with an EF of 33.5 ± 16.8 had VT with a cycle length of 326 ± 165 ms, and had 2.5± 1.6 episodes of VT in the preceding three months. 32 required shocks for that tachycardia. Results: Of these, 21 patients (16 male, 5 female Age 67±18) underwent detailed linear ablation at the scar margin in an effort to homogenize that region. This was drawn into the infarct scar by decreasing the upper voltage boundary to 2.0. In these patients, 18 showed elimination of clinical VT. In addition, 12 showed a decrease in VT from 10 ± 8.7 episodes down to 2.5 ± 1.2 episodes of actual ventricular arrhythmias. The shock requirement decreased from 8.6 ±4.7 to 1.5 ±2.7. These patients had 7 ± 3.5 different VTs at the time of ablation. These data suggest not only a decrease the occurrence of VT, but an improved control of the arrhythmia as manifested by decreased frequency of episodes and a decrease in shock. This suggests a straightforward alternative to point source ablation or to the requirement of detailed LAVA intervention. Conclusion: Linear infarct edge homogenization is a straightforward means of ablating ventricular tachycardia’s, even when unstable. This approach may be simpler than seen with LAVA interventions.

Thoracic aortic aneurysm (TAA) is a prominent condition that can progress to both aortic dissection and rupture, and has a higher prevalence in patients with bicuspid aortic valves. While smooth muscle cell proliferation and matrix remodeling are hallmarks of TAA, mechanisms regulating these phenomena are poorly understood. Thus, we tested the hypothesis that mTOR signaling, a positive regulator of cell proliferation and matrix remodeling enzyme elaboration, is increased in human TAA samples from patients with tricuspid and bicuspid aortic valves. Tissue was acquired at the time of operation, and mTOR activation was measured in aortic tissue from patients with TAA and tricuspid aortic valves (n = 29), TAA and bicuspid aortic valves (n = 29) and normal, non-aneurysmal aortic tissue from organ donors (n = 13). qRT-PCR expression of mTOR (1.29±0.1), Raptor (1.31±0.09, an mTORC1-specific subunit), and Rictor (1.44±0.1, an mTORC2-specific subunit) was significantly increased in tricuspid TAA samples compared to normal aorta (1 ±0.1; p < 0.05 for all). Similar changes were observed in patients with bicuspid TAA, as expression of mTOR (1.33±0.04), Raptor (1.27±0.06) and Rictor (1.65±0.09) were increased compared to normal (p < 0.05 for all). Importantly, protein levels of p-S6K and p-4E-BP1, both of which are well-defined targets of mTORC1 signaling, were increased by approximately two-fold in bicuspid and tricuspid TAA samples compared to normal aorta. Collectively, to our knowledge, this is the first report suggesting increased activity of both mTORC1 and mTORC2 signaling in human thoracic aortic aneurysm. We propose that inhibition of mTOR signaling may be a useful and efficacious intervention to inhibit cellular proliferation and matrix metalloproteinase activation in TAA, ultimately slowing aneurysmal dilatation and progression to aortic dissection and rupture.

Background: The extent to which tissue factor pathway inhibitor (TFPI) may regulate the extrinsic clotting cascade, atherogenesis, and MI is uncertain. Reverse genetic studies in the mouse, including deletion of the TFPI Kunitz-1 (K1) domain, have been hindered by intrauterine lethality. We sought to determine the role of TFPI in an alternative animal model, by knocking out the zebrafish ortholog tfpia . Methods and results: High-efficiency transcription activator-like effector nucleases (TALENs), targeting the 5’ region of tfpia, were microinjected into 1-cell zebrafish embryos. Sequence analysis of genomic DNA derived from adult caudal fin tissue revealed indels causing a frameshift mutation and premature stop codon prior to K1. Somatic mutants were outcrossed to WT fish, and the embryos were screened for germline mutations. Founders (F 1 ) were raised and incrossed to produce embryos (F 2 ), including approximately 25% with the desired biallelic null mutation ( tfpia -/- ) that were physically and developmentally indistinguishable, but functionally disparate from heterozygous ( tfpia +/- ) or WT ( tfpia +/+ ) siblings. At 6 days post-fertilization (dpf), F 2 tfpia -/- larvae exhibited a reduction in time to occlusion of the dorsal aorta after exposure to ferric chloride, which was more significant in 6-dpf F 3 tfpia -/- larvae (generated by incrossing F 2 tfpia -/- adults) lacking a possible maternal effect. Furthermore, F 2 tfpia -/- fish had in vivo evidence of increased fatty streaking as late larvae, after receiving a high cholesterol diet, and enhanced cardiac injury as adults, 4 days after cryoinjury-induced MI. Conclusions: Deletion of tfpia does not significantly effect zebrafish development, but leads to hypercoagulability in early larvae, enhanced atherogenesis in late larvae, and increased injury related to MI in adults, indicating a fundamental role for TFPI in the pathogenesis of cardiovascular disease.

Background: Non-cardiac surgery (NCS) in patients with severe aortic stenosis has traditionally been associated with high perioperative mortality. Aortic valve replacement is recommended prior to elective NCS, but the impact of this strategy has not been systematically assessed. Methods: A retrospective review was performed of all patients with severe aortic stenosis undergoing major NCS at Mayo Clinic between 2000 and 2013. Patients undergoing aortic valve intervention (AVI) prior to NCS were compared to those undergoing surgery without prior AVI (control). Patients undergoing emergency surgery were excluded. Primary endpoint was occurrence of major adverse cardiac events (MACE; combination of death, stroke, myocardial infarction, new/worsening heart failure, ventricular arrhythmia) within 30 days of NCS; secondary endpoints were mortality at 30 days and 1 year after NCS. Results: 180 patients (age 74.5 ± 10.5 years, 64% male) who underwent NCS within 12 months after AVI, were compared to 232 patients (age 76.6 ± 10.7 years, 56% male) in the control group. Patients undergoing AVI were more often symptomatic than controls (41% vs 26%, p = 0.002). MACE was significantly higher in the control group (21.6% vs 5.6%, p < 0.001), mainly due to the increased risk of heart failure in the postoperative period in this group (18.5% vs 2.2%, p < 0.001). There was no significant difference in the rate of myocardial infarction (1.7% vs 0.6%, p = 0.39), ventricular arrhythmia (0.9 % vs 0 %, p = 0.51) or stroke (0.9 % vs 0 %, p = 0.51). Kaplan-Meier assessment demonstrated no significant difference at 30 days but a reduction in 1 year mortality in the AVI group compared to the control group (Figure). Conclusions: Pre-operative AVI for severe aortic stenosis results in reduced heart failure and improved 1 year survival. However, other MACE and 30 day mortality appears unchanged. Pre-operative AVI should be considered in symptomatic patients, where the benefit of AVI is demonstrated to be greatest.

Introduction: The treatment options for high and extreme-risk patients with severe symptomatic aortic stenosis have changed significantly over the past decade because of advances in transcatheter aortic valve replacement (TAVR). However new permanent pacemaker implant (PPI) remains an impending concern after TAVR. Hypothesis: We sought to determine the frequency, predictors and outcomes of patients requiring PPI after TAVR. Methods: We queried the National Inpatient Sample (NIS) database using the ICD-9-CM procedure code of 35.05 for transfemoral/transaortic and 35.06 for transapical replacement of aortic valve .We identified TAVR procedures associated with new permanent pacemaker implants using appropriate validated ICD-9-CM codes. Using multivariate analysis we further identified predictors of PPM implants Results: An estimated 8828 TAVR procedures were performed in United States between 2011-2012. 773 (8.7%) TAVR procedures were associated with PPIs. PPI were higher in older (age>80 years), White race, diabetics, left bundle branch block (LBBB), right bundle branch block (RBBB), transfemoral approach. The inhospital mortality ( 5.2% vs.4.6% ) , mean length of stay ( 9.8 vs. 8.3 days ) disposition to short term nursing facility was higher (38.2% vs. 32.1%) and mean total costs (82217$ vs. 52283$) was higher in TAVR + PPI group . On multivariate analysis, Age in 5 year increment [Odds ratio (OR) 1.11; Confidence interval (CI) 1.05-1.17, p<0.001], diabetes [OR 1.26; CI 1.07-1.49, p<0.001], LBBB [OR 1.99; CI 1.55-2.56, p<0.001], RBBB [OR 5.36; CI 3.80-7.55, p<0.001] were independent predictors of PPI. Transfemoral approach was associated with more PPI implants [OR 1.41; CI 1.12 -1.78, p<0.001] Conclusion: Age, baseline conduction system disturbances, diabetes, transfemoral approach emerged as independent predictors of PPI after TAVR. This study provides useful tools to identify high-risk patients for PPI after TAVR.