Citations

Introduction: Clinical outcomes of FFR-guided PCI have been superior to those of angiographically guided PCI, with or without prior cardiac stress testing. Based on these findings, we hypothesized that the accuracy of stress testing is inferior to that of FFR in determining the physiologic significance of angiographic coronary artery disease. Method: To that end, we studied 243 consecutive patients who underwent coronary angiography and FFR assessment between September 2010 and April 2013 at Mayo Clinic, Florida. Out of this group, we excluded 143 patients due to absence of stress testing in the preceding 6 months. We assessed demographics, coronary risk factors, symptoms, stress test variables, angiographic data, and FFR measurements. FFR values ≤0.80 were considered to be positive for ischemia. We evaluated the diagnostic performance of stress testing vs. FFR. Result: Out of the 100 patients included in the study, FFR was measured in the Left Main coronary artery in 3(3%), in the Left Anterior Descending artery (LAD) in 67(67%), in the left circumflex territory in 11(11%), in the Right Coronary Artery (RCA) in 18(18%). The diagnostic performance of stress testing vs. FFR is summarized in the table, with regards to presence of ischemia in any vascular territory and with regards to a specific vascular territory. Conclusion: Compared to FFR, cardiac stress testing has reasonable NPV but poor PPV in determining the presence of absence of overall ischemia in a given patient. Most concerning, however, is that stress testing has poor PPV and NPV when used to determine the site of ischemia in a specific vascular territory.

Background: In the simulation setting, chest compression (CC) quality is reduced when out-of-hospital cardiac arrest “patients” are prepared for transport (i.e. packaged and moved to ambulance). It is unknown whether use of real-time audiovisual CPR feedback (RTAVF) affects manual CC quality when the patient is prepared for transport during actual out-of-hospital resuscitations. We tested the hypothesis that CC quality during patient transfer would be better when using RTAVF. Methods: CC quality was monitored at two EMS agencies using an E Series monitor/defibrillator with CC sensing capability (ZOLL Medical) during the treatment of consecutive out-of-hospital cardiac arrest patients who received CC on scene and were transported with ongoing CC. Data were collected during study phases; P1: RTAVF disabled, P2: RTAVF enabled following scenario-based training. Student’s t-test and Wilcoxon-Mann Whitney tests were used to compare CC quality in P1 vs. P2 during early scene and late scene treatment. Late scene was defined as the 3 minutes prior to transport (when packaging and transfer to the ambulance occurs) and early scene was all prior minutes at the scene. Results: 211 cardiac arrest cases were included: mean age 64±15 yrs, 67% male, 8% survival to hospital discharge. The Table shows that CC quality was superior during both early scene and late scene treatment in P2, when RTAVF was enabled, vs. P1, when RTAVF was disabled. Conclusion: CC quality, particularly the CC fraction, declines when a patient is packaged for transport and moved to the ambulance. While this decline is not prevented by RTAVF, CC quality during the late scene period is significantly better when using RTAVF. Further study is required to determine the impact of this improvement on outcomes.

Background and Objectives: There are a growing number of Hispanic citizens in the US and language or other barriers may impede them receiving bystander CPR (BCPR). Our aim was to determine if there are differences in BCPR provision and outcomes for out-of-hospital cardiac arrest (OHCA) occurring in mainly Hispanic neighborhoods compared to mainly White non-Hispanic neighborhoods in Arizona. Methods: We analyzed our prospectively-collected statewide Utstein-compliant OHCA database between 1/1/10 - 12/31/11. OHCA cases were geocoded according to the incident address using ArcGIS 10.1 (Esri, Redlands, CA). Census-tract data was used to determine neighborhood characteristics of ethnicity. Neighborhoods were classified as mainly Hispanic or mainly White, non-Hispanic when each population was over 60% in the census-tract. Results: There were 4531 adult OHCA victims during the study. Cases were excluded from analysis (n=1380) due to incident location, cause of arrest, or because the arrest occurred after EMS arrival. Among 3151 cases, 2839 cases (90.1%) could be geocoded using incident address. CPR performance and outcomes by neighborhood ethnicity are shown (Table). When compared with patients who arrested in mainly White, non-Hispanic neighborhoods, those in mainly Hispanic neighborhoods were less likely to receive BCPR (odds ratio, 0.67; 95% confidence interval [CI], 0.52 to 0.84). Although no statistically significant differences were identified in the rate of survival to hospital discharge by main neighborhood ethnicity, patients who arrested in mainly Hispanic neighborhoods were less likely to have favorable neurologic outcomes (Cerebral Performance Score 1 or 2) than those in White, non-Hispanic neighborhoods (odds ratio, 0.16; 95% CI, 0.05 - 0.53). Conclusion: In Arizona, OHCA victims in mainly Hispanic neighborhoods received BCPR less frequently and had worse neurologic outcomes than those in mainly White, non-Hispanic neighborhoods.

Background: CPR quality is closely linked to outcome in cardiac arrest. The AHA 2010 Guidelines recommend monitoring CPR quality performed by healthcare providers both inside and outside the hospital. However, most EDs currently do not monitor CPR quality. The goal of the present investigation was to assess the quality of CPR performed in an urban ED and determine the influence of training and real-time audiovisual feedback (RTAVF) on CPR quality and patient outcome. Methods: CPR quality was monitored using an R Series defibrillator (ZOLL Medical) during the treatment of adult cardiac resuscitation attempts. During phase 1 (P1; 11/2010-11/2012), real-time audiovisual chest compression feedback was disabled. During phase 2 (P2; 11/2012-3/2013), clinicians underwent a 60 minute didactic/hands-on CPR training session after which the RTAVF and the ECG artifact filtering feature were enabled. CPR quality data (fraction, depth, rate, release, peri-shock pause) were reviewed using Code Review software (ZOLL Medical). Student’s t-test and Wilcoxon-signed rank test were employed. Results: A total of 44 OHCA patients were treated in P1 (mean age 57±18 yrs, 59% male) and 24 in Phase 2 (mean age 63±15 yrs, 88% male). The majority of patients (89% P1; 96% P2) suffered prehospital arrest and were transported to the ED. Chest compression (CC) depth increased from 1.8±0.5 inches in P1 to 2.3±0.4 in P2 (p<0.001), with the percentage of compressions exceeding 2 inches more than doubling from 36% in P1 to 79% in P2 (p<0.001). CC release velocity increased from 1.25±0.36 inch/sec in P1 to 1.69±0.28 in P2 (p<0.001). No significant differences were identified in CC rate (125±12 cpm P1 vs. 121±15 cpm P2, p=0.3) or CC fraction (82% P1 vs. 87% P2, p=0.1). Pre-shock pause (11.5±10.4 sec P1 vs. 8.0±6.2 P2, p=0.4) and post-shock pause (5.2±3.4 sec vs. 3.8±0.6, p=0.9) were statistically similar in P1 and P2. Conclusion: The bundle of real time audiovisual CPR feedback and training were associated with an improvement in chest compression depth and recoil and closer adherence to guidelines for CPR quality in this large urban ED.

Background: Left atrial (LA) size increases in atrial fibrillation (AF). How changes in mitral annulus and atrial volume over time relate to severity of mitral regurgitation (MR) is unknown. Methods: This cohort study included 160 patients with a history of permanent AF who had at least 2 transthoracic echocardiograms (TTE) performed between 2005 and 2010 at Vancouver General Hospital (British Columbia, Canada). Patients with structural mitral valve disease, congenital heart disease, more than mild-moderate mitral/tricuspid regurgitation on their first TTE were excluded from analyses. LA volume was determined using biplane area-length method, averaged over 3 cardiac cycles. The mitral annulus diameter (MAD), defined as the distance between the hinge points of the anterior and posterior mitral leaflets from the apical 4-chamber view, was measured during end-systole and end-diastole. Linear mixed effects modeling was used in analyzing the above measurements for change over time. Mitral regurgitation was classified into 3 grades (mild, moderate, or severe) using standard color Doppler and PISA easurements where available. Results: Of the 160 subjects included in this analysis, 100 were men (62.5%). The mean age at study entry was 74±10 years. The median number of TTE performed was 3 (range 2 - 6). All 160 patients showed a progressive increase in MAD over time. There was a significant increase in MAD at end-systole and end-diastole over a mean follow-up of 3.2 ± 2.8 years; the increases were 0.48 mm/year (95% CI 0.124 -0.75, P=0.0037) and 0.45 mm/year (95% CI 0.102-0.716, P=0.0029) respectively. LA volume increased from a mean of 43 mL/m2 to 75 mL/m2 for the cohort, or 10 mL/m2 per year. Adjusting for age, sex, and left ventricular ejection fraction, an increase in MR severity by at least 1 grade was strongly and independently associated with an increase in MAD. A 15% increment in MAD was associated with an increase in MR severity by 1 grade. Conclusion: Permanent AF was associated with significant increases in MAD and LA volume over time. Severity of MR also significantly increased over time, and was independently related to the change in MAD. Further investigations as to whether this represents a mechanism for left heart failure in patients with permanent AF are warranted.

Site specific targeting remains an elusive goal for stem cell and gene therapies in the cardiovascular field. One promising option involves use of modified 3D stent designs that deliver larger cell/gene payloads to specific disease sites using the versatility of percutaneous vascular access. Here, we engineered smooth muscle cells (SMCs) placed in a 3D metallic stent scaffold to deliver high local concentrations of an angiogenic gene (VEGF165) in a porcine model of chronic total occlusion involving ameroid placement on the proximal left circumflex (LCx) artery(n≥8 per group). Engineered SMCs were retained within the mesh stent structure (479 ± 47.4 SMC/mm2) and were competent for VEGF production in vitro (8.8 ± 1.8 ng/ml in media). Following implantation, micro CT analyses revealed that stents loaded with VEGF producing SMCs significantly enhanced vasa vasora microvessel density (5.43 ± 0.46 vs 2.14 ± 0.19 vessels/mm2, p<0.001) with a concomitant increase in tissue VEGF protein levels (277.9 ± 85.7 vs 18.8 ± 4.4 pg/mg protein, p<0.0001). Formation of endothelial cell colonies from peripheral blood mononuclear cells was significantly increased with the implantation of VEGF-secreting cells suggesting increased angiogenic potential (7.0 ± 2.0 versus 41.6 ± 4.5, EC:CFU p<0.0001). VEGF secreting mesh stent placement enhanced regional blood flow analyses determined by microsphere analyses as well as improving regional wall motion in the LCx-related territory (p<0.05) as well as left ventricular function assessed in terms of ejection fraction (34.2 ± 6.7% vs 61.2 ± 5.2% P<0.001) and dp/dt (p<0.001) Our data indicate robust clinically relevant angiogenesis can be achieved in a human scale porcine chronic vascular occlusion model following stent based delivery of angiogenic cells. This may have implications for percutaneous delivery of stem cells, genes and secreted therapeutic factors in cardiovascular disease in general and in creation of percutaneous microvascular bypass networks in the setting of chronic vaso-occlusive disease in particular.

Aortic stenosis is the most common acquired valvular heart disease. Currently, there are no medications approved to slow its progression. We set out to investigate the effect of ACE inhibitors/angiotensin receptor blockers and aldosterone antagonists on the rate of progression of mild aortic stenosis. We retrospectively reviewed the charts of 2,613 patients over 45 years old, who had a peak velocity between 1.8 and 3 meters/second on initial echo. Over 8 years of followup, 491 patients were prescribed angiotensin converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs) and 130 patients were prescribed aldosterone receptor blockers. Patients prescribed ACE inhibitors/ARBs had a slower rate of progression of aortic stenosis compared to those not prescribed ACE inhibitors/ARBs (2.2 to 2.5 vs. 2.3 to 2.8 meters/second) (Figure 1). Also, patients prescribed aldosterone receptor blockers had a slower rate of progression of aortic stenosis compared to those who were not 2.2 to 2.4 vs. 2.3 to 2.8 meters/second) (Figure 2). Our findings suggest that angiotensin or aldosterone antagonism is associated with slower rate of progression of mild aortic stenosis.

Background: CP/R-CP may be associated with subtle features of ventricular dysfunction which are not easily detectable with the use of conventional echocardiographic modalities. The aim of this study was to evaluate myocardial mechanics by 2D-STE (2 Dimensional speckle-tracking echocardiography) between CP and R-CP. We hypothesized that strain/ strain rate (S/SR) would be worse in the R-CP patients due to radiation-induced myocardial injury. Methods: We analyzed 180 patients (62% male, age 62±13 years, 127 CP and 53 R-CP) with suitable echocardiographic images and normal left ventricular ejection fraction (LVEF>55%). The two groups were similar in terms of age, cardiovascular symptoms, risk factor profile and LVEF (Table). Selected images were analyzed off-line using Velocity Vector Imaging technology. The diagnosis of CP was based on clinical parameters as well as echocardiography and/or hemodynamic cardiac catheterization. Patients in whom radiation therapy was the primary etiology of CP were classified as R-CP. Global and segmental circumferential, radial, longitudinal, systolic and early diastolic strain and strain rate were analyzed in all patients. Results: Global and segmental radial (GRadS), global longitudinal (GLS), global basal (GBS), global mid-segment (GMS), septal wall (SWS), and anterior wall (AWS) strain was significantly reduced in the R-CP patients compared with the CP patients (Table). Antero-septal and anterior wall diastolic strain and strain rates (AS + AW Sre, SR) were reduced in the R-CP group. The best differentiators between the two groups were antero-septal (SAS), basal anterior (BAS) and mid anterior (MAS) segmental strain, based on receiver operating characteristic (ROC) and area under the curve (AUC) analysis. ROC calculations were AUC: SAS 0.67, SBA 0.69, and SMA 0.71. Conclusion: The study showed that compared with CP, R-CP is associated more with myocardial dysfunction, likely due to radiation-induced myocardial injury.

Introduction: Aortic valve replacement approaches have shifted towards catheter-based therapies in older patients. While this strategy is appropriate in extreme risk cases, concerns regarding aortic insufficiency(AI)/paravalvular leak and stroke with catheter valves may favor use of surgical aortic valve replacement in intermediate and low risk patients. We present outcomes of intermediate risk octogenarian patients undergoing surgical aortic valve replacement enrolled in a prospective trial with robust endpoint assessment and follow-up. Methods: The St. Jude Trifecta IDE trial was a prospective approval study for a new aortic valve prosthesis. The Trifecta bioprosthesis was implanted in 210 pts over 80 years of age between 2007 and 2009 at 28 centers in the US, Canada, and Europe. Mean age was 83.5 ± 2.7 years(range 80-95) of which 103[49.0%] were female. 62[29.5%] subjects had undergone previous cardiac surgery. Concomitant CABG was performed in 103 [49.0%] patients. Results: The mean STS predicted mortality score was 4.02 +/- 2.16. Follow-up was 399.4 late patient-years. Early (≤ 30 day) mortality occurred in 3 [1.4%] patients and there were 17 late (≥ 31 days) deaths yielding a survival of 91.7% at 2 years and 87.1% at 3 years. There was no paravalvular leak, valve thrombosis, early endocarditis or hemolysis. There were 7 early neurologic events including 2 [1.0%] strokes, and 5 [2.4%] reversible neurologic events. There were 9 late thromboembolic events, including 3 strokes and 6 reversible neurologic events or transient ischemic attacks (linearized rate 2.25%/year of follow-up). Freedom from valve explant was 99.4% at 3 years. Mean gradient and effective orifice area at 3 year follow-up was 10.2 mmHg +/- 5.0 and 1.43 cm2 +/- 0.26, respectively. 88.9% of patients demonstrated none or trivial AI, 2.2% and 0% demonstrated moderate and severe AI, respectively. Conclusions: In conclusion, surgical valve replacement in elderly intermediate risk patients demonstrates superb clinical outcomes and results. Extremely low rates of stroke and aortic insufficiency in combination with excellent 3-4 year survival show a favorable profile for intermediate risk patients to undergo surgical aortic valve replacement.

Background: Next-Generation Sequencing (NGS) allows for sequencing of a many genes simultaneously, leading genetic testing companies to provide sequencing of all genes associated with a particular disease in large gene test panels. For example, there are over 90 distinct genes associated with premature sudden arrhythmic death. Previous publiclations have shown a background rate of rare non-synonymous single nucleotide variants (nsSNVs) in many of these genes which may be compounded when included in large gene panels. Therefore, we hoped to determine this background rate of nsSNVs in 93 genes that comprise various sudden death genetic heart disease genetic test panels. Methods: The exomes from the 1000 Genomes Project (1kG) and the NHLBI Exome Sequencing Project (ESP) were genotyped in-silico for nsSNVs in 93 genes indentified on clinically available genetic tests available for HCM, DCM, ARVC, LQTS, SQTS, BrS, and CPVT. The number of subjects hosting an exceedingly rare and unique nsSNV was determined for each gene. Results: Strikingly, 40.8% of the 1 kG cohort (12.5% hosted > 2 unique nsSNVs) and 41.9% of the ESP cohort possessed > 1 rare nsSNV within the entire 93 gene panel, while the yield of rare nsSNVs in individual genes only ranged from 0.02% for PLN to 2.3% for DMD. This background rate directly correlated with the number of genes on the panel (r=0.97). When limited to only those genes that account for >10% of the disease (HCM - MYBPC3, MYH7; LQTS - KCNQ1, KCNH2; ARVC - PKP2, DSG2; CPVT - RYR2; BrS - SCN5A), at least 7% of the subjects in both cohorts had at least one nsSNV. Thus, nearly 90% of the background rate is contained within the minor disease-susceptibility genes. Conclusions: Despite not being enriched for the presence of genetic channelopathies and cardiomyopathies, two out of every 5 subjects within these cohorts hosted at least 1 ultra-rare nsSNV within the 93 known channelopathy/cardiomyopathy-susceptibility genes. Despite the anticipated transition from disease-specific genetic testing to whole exome genetic testing, great caution must be exercised to glean the true pathogenic mutation amidst this very daunting burden of background genetic noise. If handled poorly, false positive genetic test results and misguided cascade screens will increase.