Peyman Benharash

Quantitative Analysis of Localized Sources Identified by Focal Impulse and Rotor Modulation Mapping in Atrial Fibrillation

Background—New approaches to ablation of atrial fibrillation (AF) include focal impulse and rotor modulation (FIRM) mapping, and initial results reported with this technique have been favorable. We sought to independently evaluate the approach by analyzing quantitative characteristics of atrial electrograms used to identify rotors and describe acute procedural outcomes of FIRM-guided ablation. Methods and Results—All FIRM-guided ablation procedures (n=24; 50% paroxysmal) at University of California, Los Angeles Medical Center were included for analysis. During AF, unipolar atrial electrograms collected from a 64-pole basket catheter were used to construct phase maps and identify putative AF sources. These sites were targeted for ablation, in conjunction with pulmonary vein isolation in most patients (n=19; 79%). All patients had rotors identified (mean, 2.3±0.9 per patient; 72% in left atrium). Prespecified acute procedural end point was achieved in 12 of 24 (50%) patients: AF termination (n=1), organization (n=3), or >10% slowing of AF cycle length (n=8). Basket electrodes were within 1 cm of 54% of left atrial surface area, and a mean of 31 electrodes per patient showed interpretable atrial electrograms. Offline analysis revealed no differences between rotor and distant sites in dominant frequency or Shannon entropy. Electroanatomic mapping showed no rotational activation at FIRM-identified rotor sites in 23 of 24 patients (96%). Conclusions—FIRM-identified rotor sites did not exhibit quantitative atrial electrogram characteristics expected from rotors and did not differ quantitatively from surrounding tissue. Catheter ablation at these sites, in conjunction with pulmonary vein isolation, resulted in AF termination or organization in a minority of patients (4/24; 17%). Further validation of this approach is necessary.

Long-term clinical outcomes of focal impulse and rotor modulation for treatment of atrial fibrillation: A multicenter experience

BACKGROUND New approaches to ablation of atrial fibrillation (AF) include focal impulse and rotor modulation (FIRM). Studies of this technology with short-term follow-up have shown favorable outcomes. OBJECTIVE The purpose of this study was to characterize the long-term results of FIRM ablation in a cohort of patients treated at 2 academic medical centers. METHODS All FIRM-guided ablation procedures (n = 43) at UCLA Medical Center and Virginia Commonwealth University Medical Center performed between January 2012 and October 2013 were included for analysis. During AF, FIRM software constructed phase maps from unipolar atrial electrograms to identify putative AF sources. These sites were targeted for ablation, along with pulmonary vein isolation in 77% of patients. RESULTS AF was paroxysmal in 56%, and 67% had prior AF ablation. All patients had rotors identified (mean 2.6 ± 1.2 per patient, 77% in LA). Prespecified acute procedural end-point was achieved in 47% of patients (n = 20): AF termination in 4, organization in 7, >10% slowing of AF cycle length in 9. Acute complications occurred in 4 patients (9.3%). At 18 ± 7 months of follow-up, 37% were free from documented recurrent AF after a 3-month blanking period; 21% were free from documented atrial tachyarrhythmias and off antiarrhythmic drugs. Multivariate analysis did not reveal any significant predictors of AF recurrence, including pattern of AF, acute procedural success, or prior failed ablation. CONCLUSION Long-term clinical results after FIRM ablation in this cohort of patients showed poor efficacy, different from previously published studies. Randomized studies are needed to evaluate the efficacy and clinical utility of this ablation approach for treating AF.

Lateral Movement of Endografts Within the Aneurysm Sac Is an Indicator of Stent-Graft Instability

Purpose: To determine if lateral movement of an aortic endograft 1 year following endovascular abdominal aortic aneurysm (AAA) repair is an indicator of endograft instability and can serve as a predictor of late adverse events. Methods: The records of 60 high-risk AAA patients (52 men, 8 women; mean age 74 years) who were treated with infrarenal (n=38) or suprarenal (n=22) endografts and had serial computed tomograms (CT) over ≥12 months were analyzed. Postimplantation and 1-year CT scans were compared, and changes in endograft position within the aneurysm sac [lateral movement (LM) versus no lateral movement (NM)] were measured using a vertebral body reference point. Longitudinal endograft movement was measured with respect to the superior mesenteric artery along the aortic centerline axis. Long-term adverse event rates (endoleaks, secondary procedures, conversion, rupture, and death) were assessed. Results: One year after endograft implantation, LM ≥5 mm was present in 16 (27%) patients; 44 (73%) endografts demonstrated no lateral movement. LM patients had larger aneurysms (6.5±1.5 versus 5.6±0.9 cm, p=0.02) and a longer endograft—to—hypogastric artery length (p=0.01) than NM patients. There were no significant differences between patients treated with infrarenal and suprarenal endografts. At 1 year, longitudinal migration ≥10 mm occurred in 5 (31%) of the LM patients versus 2 (5%) in the NM cohort (p<0.0001). There were no significant differences in adverse event rates between LM and NM at 1 year. However, during long-term follow-up (mean 54±26 months, range 12–102), 8 (50%) LM patients developed a type I endoleak versus 8 (18%) NM patients (p=0.02), and 12 (75%) LM patients required a secondary procedure versus 9 (20%) NM patients (p=0.0002). One (6%) LM patient experienced aneurysm rupture and 2 (13%) other LM patients underwent conversion to open repair. Conclusion: Lateral endograft movement within the aneurysm sac at 1 year is associated with increased risk of late adverse events and was at least as good a predictor of these complications as was longitudinal migration.

Cardioprotection of electroacupuncture against myocardial ischemia-reperfusion injury by modulation of cardiac norepinephrine release

Augmentation of cardiac sympathetic tone during myocardial ischemia has been shown to increase myocardial O(2) demand and infarct size as well as induce arrhythmias. We have previously demonstrated that electroacupuncture (EA) inhibits the visceral sympathoexcitatory cardiovascular reflex. The purpose of this study was to determine the effects of EA on left ventricular (LV) function, O(2) demand, infarct size, arrhythmogenesis, and in vivo cardiac norepinephrine (NE) release in a myocardial ischemia-reperfusion model. Anesthetized rabbits (n = 36) underwent 30 min of left anterior descending coronary artery occlusion followed by 90 min of reperfusion. We evaluated myocardial O(2) demand, infarct size, ventricular arrhythmias, and myocardial NE release using microdialysis under the following experimental conditions: 1) untreated, 2) EA at P5-6 acupoints, 3) sham acupuncture, 4) EA with pretreatment with naloxone (a nonselective opioid receptor antagonist), 5) EA with pretreatment with chelerythrine (a nonselective PKC inhibitor), and 6) EA with pretreatment with both naloxone and chelerythrine. Compared with the untreated and sham acupuncture groups, EA resulted in decreased O(2) demand, myocardial NE concentration, and infarct size. Furthermore, the degree of ST segment elevation and severity of LV dysfunction and ventricular arrhythmias were all significantly decreased (P < 0.05). The cardioprotective effects of EA were partially blocked by pretreatment with naloxone or chelerythrine alone and completely blocked by pretreatment with both naloxone and chelerythrine. These results suggest that the cardioprotective effects of EA against myocardial ischemia-reperfusion are mediated through inhibition of the cardiac sympathetic nervous system as well as opioid and PKC-dependent pathways.

P19 Progenitor Cells Progress to Organized Contracting Myocytes after Chemical and Electrical Stimulation: Implications for Vascular Tissue Engineering

Purpose: To test the hypothesis that a level of chemical and electrical stimulation exists that allows differentiation of progenitor cells into organized contracting myocytes. Methods: A custom-made bioreactor with the capability of delivering electrical pulses of varying field strengths, widths, and frequencies was constructed. Individual chambers of the bioreactor allowed continuous electrical stimulation of cultured cells under microscopic observation. On day 0, 1% dimethylsulfoxide (DMSO), known to differentiate cells into myocytes, was added to P19 progenitor cells. Additionally, for the next 22 days, electrical pulses of varying field strengths (0–3 V/cm), widths (2–40 ms), and frequencies (10–25 Hz) were continuously applied. On day 5, the medium containing DMSO was exchanged with regular medium, and the electrical stimulation was continued. From days 6–22, the cells were visually assessed for signs of viability, contractility, and organization. Results: P19 cells remained viable with pulsed electrical fields <3 V/cm, pulse widths <40 ms, and pulse frequencies from 10 to 25 Hz. On day 12, the first spontaneous contractions were observed. For individual colonies, local synchronization and organization occurred; multiple colonies were synchronized with externally applied electrical fields. Conclusion: P19 progenitor cells progress to organized contracting myocytes after chemical and electrical stimulation. Incorporation of such cells into existing methods of producing endothelial cells, fibroblasts, and scaffolds may allow production of improved tissue-engineered vascular grafts.

Functional differences between junctional and extrajunctional adrenergic receptor activation in mammalian ventricle

Increased cardiac sympathetic activation worsens dispersion of repolarization and is proarrhythmic. The functional differences between intrinsic nerve stimulation and adrenergic receptor activation remain incompletely understood. This study was undertaken to determine the functional differences between efferent cardiac sympathetic nerve stimulation and direct adrenergic receptor activation in porcine ventricles. Female Yorkshire pigs (n = 13) underwent surgical exposure of the heart and stellate ganglia. A 56-electrode sock was placed over the ventricles to record epicardial electrograms. Animals underwent bilateral sympathetic stimulation (BSS) (n = 8) or norepinephrine (NE) administration (n = 5). Activation recovery intervals (ARIs) were measured at each electrode before and during BSS or NE. The degree of ARI shortening during BSS or NE administration was used as a measure of functional nerve or adrenergic receptor density. During BSS, ARI shortening was nonuniform across the epicardium (F value 9.62, P = 0.003), with ARI shortening greatest in the mid-basal lateral right ventricle and least in the midposterior left ventricle (LV) (mean normalized values: 0.9 ± 0.08 vs. 0.56 ± 0.08; P = 0.03). NE administration resulted in greater ARI shortening in the LV apex than basal segments [0.91 ± 0.04 vs. 0.63 ± 0.05 (averaged basal segments); P = 0.003]. Dispersion of ARIs increased in 50% and 60% of the subjects undergoing BSS and NE, respectively, but decreased in the others. There is nonuniform response to cardiac sympathetic activation of both porcine ventricles, which is not fully explained by adrenergic receptor density. Different pools of adrenergic receptors may mediate the cardiac electrophysiological effects of efferent sympathetic nerve activity and circulating catecholamines.

Functional assessment at the buttock level of the effect of aortobifemoral bypass surgery.

Background:Little is known about the prevalence of proximal (hip, buttock, lower back) claudication after aortobifemoral bypass (AF2B) grafting and its hemodynamic effects at the buttock level. Methods:Forty-eight patients performed a treadmill test before and within 6 months after AF2B. The San Diego Claudication Questionnaire and the chest-corrected decrease from rest of transcutaneous oxygen pressure on buttocks were used to study exercise-induced proximal claudication and regional pelvic blood flow impairment. A decrease from rest of transcutaneous oxygen pressure value <−15 mm Hg was used to indicate regional blood flow impairment (RBFI). Results:Patients had the following characteristics: 39 were men and 9 were women, 60 ± 9 years, lowest ankle-to-brachial index (ABI) of 0.55 ± 0.18 and maximal walking distance (MWD) on treadmill of 188 ± 192 m at inclusion. ABI and MWD were significantly improved after surgery at 0.83 ± 0.19 and 518 ± 359 m (P < 0.0001). Unilateral or bilateral RBFI at the buttocks was found in 39 versus 29 patients before and after AF2B, respectively. Proximal claudication with underlying RBFI on one or both sides on treadmill were observed in 29 patients before AF2B, and in 9 of 26 (41%) versus 6 of 22 (23%) patients in end-to-end versus end-to-side proximal aorto-graft anastomosis of the AF2B, respectively (P < 0.05). Conclusion:A significant increase in MWD and ABI, but little improvement of proximal perfusion is observed after surgery, a finding that is expected from the absence of hypogastric artery revascularization. The prevalence of proximal claudication and proximal blood flow impairment is higher in case of end-to-end when compared with end-to-side proximal aorto-graft anastomosis, confirming the role of collaterals such as lumbar arteries in the buttock circulation during exercise in patients suffering from peripheral arterial disease. Proximal claudication on treadmill early after surgery affects almost one third of the patients and must not be underestimated among patients receiving AF2B. Attempts at hypogastric artery revascularization, if possible, might be preferable to decrease the risk of proximal claudication after AF2B.

Effect of stellate ganglia stimulation on global and regional left ventricular function as assessed by speckle tracking echocardiography

Left ventricular (LV) twist mechanics and regional strain during cardiac sympathetic efferent activation are poorly understood. The purpose of this study was to compare the effects of left stellate ganglia (LSG) and right stellate ganglia (RSG) stimulation on cardiac twist/untiwst mechanics and regional strain. In nine pigs, echocardiographic imaging and LV pressure-volume measurements were performed before and during unilateral and bilateral stellate ganglion stimulation. LSG and RSG stimulation significantly augmented LV end-systolic pressure by 24% and 22% (P < 0.01), maximal rate of LV pressure change by 167% and 165% (P < 0.01), and time constant of LV relaxation by 20% and 12% (P < 0.01), respectively. RSG stimulation resulted in a greater chronotropic response than LSG stimulation (RSG: 68% vs. LSG: 12%, P < 0.01). Both LSG and RSG stimulation significantly increased global epicardial and endocardial LV rotation and diastolic untwisting rate and reduced the time to peak rotation (P < 0.05). However, LSG stimulation predominantly increased radial and circumferential strain in the LV inferoseptal, inferior, posterior, and lateral regions, whereas RSG stimulation primarily increased radial and circumferential strain in the anteroseptal, anterior, and lateral LV regions. Stimulation of both stellate ganglia led to a uniform increase in all LV segments. Our data suggest that LSG and RSG stimulation lead to a global increase in LV twist, driven by distinct regional strain heterogeneity that may result from myocardial innervation from the LSG and RSG. These findings provide a better understanding of the global and regional functional consequences of regional myocardial innervation from the LSG and RSG.

Improved costs and outcomes with conscious sedation vs general anesthesia in TAVR patients: Time to wake up?

Background Transcatheter aortic valve replacement (TAVR) has become a commonplace procedure for the treatment of aortic stenosis in higher risk surgical patients. With the high cost and steadily increasing number of patients receiving TAVR, emphasis has been placed on optimizing outcomes as well as resource utilization. Recently, studies have demonstrated the feasibility of conscious sedation in lieu of general anesthesia for TAVR. This study aimed to investigate the clinical as well as cost outcomes associated with conscious sedation in comparison to general anesthesia in TAVR. Methods Records for all adult patients undergoing TAVR at our institution between August 2012 and June 2016 were included using our institutional Society of Thoracic Surgeons (STS) and American College of Cardiology (ACC) registries. Cost data was gathered using the BIOME database. Patients were stratified into two groups according to whether they received general anesthesia (GA) or conscious sedation (CS) during the procedure. No-replacement propensity score matching was done using the validated STS predicted risk of mortality (PROM) as a propensity score. Primary outcome measure with survival to discharge and several secondary outcome measures were also included in analysis. According to our institutions data reporting guidelines, all cost data is presented as a percentage of the general anesthesia control group cost. Results Of the 231 patients initially identified, 225 (157 GA, 68 CS) were included for analysis. After no-replacement propensity score matching, 196 patients (147 GA, 49 CS) remained. Overall mortality was 1.5% in the matched population with a trend towards lower mortality in the CS group. Conscious sedation was associated with significantly fewer ICU hours (30 vs 96 hours, p = <0.001) and total hospital days (4.9 vs 10.4, p<0.001). Additionally, there was a 28% decrease in direct cost (p<0.001) as well as significant decreases in all individual all cost categories associated with the use of conscious sedation. There was no difference in composite major adverse events between groups. These trends remained on all subsequent subgroup analyses. Conclusion Conscious sedation is emerging as a safe and viable option for anesthesia in patients undergoing transcatheter aortic valve replacement. The use of conscious sedation was not only associated with similar rates of adverse events, but also shortened ICU and overall hospital stays. Finally, there were significant decreases in all cost categories when compared to a propensity matched cohort receiving general anesthesia.

Left ventricular twist and untwist rate provide reliable measures of ventricular function in myocardial ischemia and a wide range of hemodynamic states

Although rotational parameters by speckle tracking echocardiography (STE) have been previously compared to sonomicrometry and cardiac magnetic resonance imaging, few have examined the relationship between left ventricular (LV) rotational mechanics and intraventricular measures of load‐independent contractility, LV stiffness, or ventriculoarterial coupling. The aim of this study was to compare the changes in LV rotational indices to intraventricular pressure–volume (PV) relationships under a range of inotropic states induced by pharmacological interventions, acute ischemia, and changes in preload. In nine pigs, simultaneous echocardiographic imaging and LVPV measurements were performed during pharmacologically induced high or low inotropy and during acute ischemia by ligation of the left anterior descending coronary artery (LAD). Maximal ventricular elastance (Emax), arterial elastance (Ea), ventricular–arterial coupling (Emax/Ea), dP/dt, tau, and other hemodynamic parameters were determined. Dobutamine and esmolol infusions led to inversely correlated changes in hemodynamic measurements of LV function. Apical but not basal rotation and diastolic rotation rate were decreased by esmolol and increased by dobutamine. The LV twist correlates well with Emax (r = 0.83) and Emax/Ea (r = 0.80). Apical diastolic rotation rate also correlates with dP/dtmin (r = −0.63), τ (r = −0.81), and LV stiffness (r = −0.52). LAD ligation decreased systolic and diastolic LV rotation in apical (P < 0.05), but not basal myocardium. Occlusion of the inferior vena cava, to reduce preload, increased apical rotation in systole and diastole. LV rotational parameters measured by STE provide quantitative and reproducible indices of global LV systolic and diastolic function during acute changes in hemodynamics.