Strain Analysis in Patients with Frequent Premature Ventricular Complexes and Preserved Left Ventricular Function Undergoing Ablation.

BACKGROUND: Frequent premature ventricular complexes (PVCs) can cause PVC-induced cardiomyopathy. The value of PVC ablation in patients with preserved left ventricular function in the low-normal range (ejection fraction: 50-55%) is not established. Strain analysis has been used to estimate changes in left ventricular function beyond assessment of the ejection fraction (EF). Longitudinal strain has been proposed as a method to detect changes over time in the setting of frequent asymptomatic premature ventricular complexes and preserved left ventricular (LV) function. A decrease in strain may be evidence of PVC-induced cardiomyopathy. OBJECTIVE: In this study, we assessed the role of PVC ablation in patients with low-normal EF and the effect on EF and myocardial strain before and after PVC ablation. METHODS: A total of 70 consecutive patients with either low-normal EF (0.5-<0.55, n = 35) or high-normal EF (≥0.55; n = 35), using available imaging and Holter data, were referred for ablation due to frequent PVCs. EF and longitudinal strain were assessed pre- and post-ablation. RESULTS: There was a significant increase in EF (53.2 ± 0.4% to 58.3 ± 0.5%, p < 0.001) and improvement in longitudinal strain (-15.2 ± 3.3 to -16.6 ± 3, p = 0.007) post-ablation in patients with low-normal EF and successful ablation. There was no change in EF or longitudinal strain in patients with high-normal EF and a successful ablation pre- vs. post-ablation. CONCLUSIONS: Patients with frequent PVCs and low-normal LV EF compared to patients with frequent PVCs and high-normal LV EF have evidence of PVC-induced cardiomyopathy and may benefit from ablation despite a preserved left ventricular EF.

Outcomes in patients with electrocardiographic left ventricular dyssynchrony following transcatheter aortic valve replacement.

BACKGROUND: Left bundle branch block (LBBB) and atrioventricular (AV) conduction abnormalities requiring permanent pacemaker (PPM) implantation occur frequently following transcatheter aortic valve replacement (TAVR). The resultant left ventricular (LV) dyssynchrony may be associated with adverse clinical events. OBJECTIVES: The purpose of this study was to assess the adverse outcomes associated with LV dyssynchrony due to high-burden right ventricular (RV) pacing or permanent LBBB following TAVR in patients with preserved left ventricular ejection fraction (LVEF). METHODS: Consecutive TAVR patients at the University of Michigan from January 2012 to June 2017 were included. Pre-existing cardiac implantable electronic device, previous LBBB, LVEF <50%, or follow-up period <1 year were excluded. The primary outcome was all-cause mortality. Secondary outcomes included cardiomyopathy (defined as LVEF ≤45%), a composite endpoint of cardiomyopathy or all-cause mortality, and the change in LVEF at 1-year follow-up. RESULTS: A total of 362 patients were analyzed (mean age 77 years). LV dyssynchrony group (n = 91 [25.1%]) included 56 permanent LBBB patients, 12 permanent LBBB patients with PPM, and 23 non-LBBB patients with PPM and high-burden RV pacing. Remaining patients served as control (n = 271 [74.9%]). After adjusted analysis, LV dyssynchrony had significantly higher all-cause mortality (adjusted hazard ratio [HR] 2.16; 95% confidence interval [CI] 1.07-4.37) and cardiomyopathy (adjusted HR 14.80; 95% CI 6.31-14.69). The LV dyssynchrony group had mean LVEF decline of 10.5% ± 10.2% compared to a small increase (0.5% ± 7.7%) in control. CONCLUSION: Among TAVR patients with preserved LVEF and normal AV conduction, development of postprocedural LV dyssynchrony secondary to high-burden RV pacing or permanent LBBB was associated with significantly higher risk of death and cardiomyopathy at 1-year follow-up.

A simplified differential pacing technique for the evaluation of bidirectional cavo-tricuspid isthmus block during ablation of typical atrial flutter.

PURPOSE: Bidirectional block of the cavo-tricuspid isthmus (CTI) is an established endpoint of CTI-dependent atrial flutter (AFl) ablation. Differential pacing has been used to evaluate the CTI block. The purpose of this study is to describe a modified differential pacing technique to evaluate the CTI block. METHODS: Sixty-two patients underwent radiofrequency (RF) ablation of CTI-dependent AFl. The acute endpoints were non-inducibility of the AFl, and verification of the bidirectional CTI block by our methodology. Pacing was performed in the CS with an ablation catheter positioned immediately lateral to the CTI ablation line, and then 1-2 cm more laterally. The stimulus-to-ablation catheter atrial electrogram intervals were measured at these sites (StimCS-Abl1 and StimCS-Abl2, respectively). Pacing with the ablation catheter also was performed at these 2 sites, and the stimulus-to-CS electrogram intervals (StimABL1-CS and StimABL2-CS) were measured. The criteria for the bidirectional block were StimCS-Abl1 > StimCS-Abl2, and StimABL1-CS > StimABL2-CS. Clinical efficacy was defined as freedom from recurrent AFl during follow-up. RESULTS: Following 12.2 ± 3.7 min of RF delivery across the CTI, intervals were StimCS-Abl1 = 181.2 ± 22.7 ms and StimABL1-CS = 181.0 ± 23.6 ms, and StimCS-Abl2 = 152.2 ± 26.5 ms and StimABL2-CS = 151.2 ± 22.7 (P < 0.001). Atrial flutter was rendered not inducible in all patients, and no procedural complications were encountered. During the next 15.9 ± 0.7 months, two patients were lost to follow-up, and among the 62 other patients, one (1.7%) had flutter recurrence. CONCLUSIONS: The bidirectional CTI block can be assessed quickly and easily using only the ablation and CS catheters for differential pacing.

Lead damage after cardiac implantable device replacement procedure: Comparison between electrical plasma tool and electrocautery.

BACKGROUND: Lead damage is a complication caused by lead manipulation or heating damage from conventional electrocautery (EC) after cardiovascular implantable electronic device (CIED) replacement. Application of electrical plasma (PEAK PlasmaBlade) is a new technology that reportedly reduces this risk. OBJECTIVES: This study was designed to compare the effect of EC versus PEAK PlasmaBlade on lead parameters and complications after generator replacement procedures. METHODS: We retrospectively studied 410 consecutive patients (840 leads) who underwent CIED replacement using EC (EC group) and 410 consecutive patients (824 leads) using PEAK PlasmaBlade (PlamaBlade group). Pacing lead impedance, incidence of lead damage, and complications were compared between both groups. RESULTS: Lead impedance increased in 393 leads (46.8%) in the EC group versus 282 leads (34.2%) in the PlasmaBlade group (p < .01) with average percent changes of 6.7% and 4.0% (p < .01), respectively. Lead impedance decreased in 438 leads (52.1%) in the EC group versus 507 leads (61.5%) in the PlasmaBlade group (p < .01) with average percent changes of -5.7% and -7.1% (p < .01), respectively. Lead damage requiring lead revision occurred in five leads (0.6%) or after five procedures (1.2%) in the EC group compared to three leads (0.4%, p = .50) or after three procedures (0.7%, p = .48) in the PlasmaBlade group. There were no significant differences in the procedural-related complications between the EC group (nine patients, 2.2%) and the PlasmaBlade group (five patients, 1.2%, p = .28). CONCLUSION: Conventional electrocautery can potentially damage lead insulations. However, this study shows that when used carefully electrocautery is as safe as the PEAK PlasmaBlade™.

Catheter ablation of the left and right atrial appendages without isolation in persistent atrial fibrillation.

BACKGROUND: Electrical isolation of the left atrial appendage (LAA) improves outcomes of patients with persistent atrial fibrillation (AF) but may increase the risk of thromboembolism. OBJECTIVE: The purpose of this study was to describe a method to map and ablate appendage drivers without complete electrical isolation. METHODS: One hundred thirteen patients underwent an ablation procedure for persistent AF. The procedure was performed during AF and consisted of pulmonary vein and posterior LA isolation as well as ablation of the LAA. The right atrium (RA) was targeted in patients with a right-to-left gradient in cycle length (CL). The end point of appendage ablation was CL slowing or AF termination but not complete isolation. RESULTS: Among the 113 patients (mean age 64.6 ± 8.6 years; ejection fraction 54% ± 13%; LA diameter 46 ± 6.5 mm), radiofrequency ablation terminated AF in 51 patients (45%). RA ablation was performed in 41 patients (36%) at the index or repeat procedure. The mean AF CL in the RA appendage (RAA) was shorter than that in the LAA (160 ± 32 ms vs 186 ± 29 ms; P < .01) in these patients. The most frequent target in the RA was the RAA (CLs approaching 50-60 ms). Discontinuing radiofrequency ablation upon AF termination or conduction slowing prevented LAA isolation. After a mean follow-up of 24 ± 15 months, 89 patients (78%) remained arrhythmia-free without antiarrhythmic medications. CONCLUSION: An ablation strategy guided by the AF CL addresses LAA drivers without complete electrical isolation and also helps identify the RAA as a source of persistent AF.

Baseline and decline in device-derived activity level predict risk of death and heart failure in patients with an ICD for primary prevention.

BACKGROUND: Implanted defibrillators are capable of recording activity data based on company-specific proprietary algorithms. This study aimed to determine the prognostic significance of baseline and decline in device-derived activity level across different device companies in the real world. METHODS: We performed a retrospective cohort study of patients (n = 280) who underwent a defibrillator implantation (Boston, Medtronic, St. Jude, and Biotronik) for primary prevention at the University of Michigan from 2014 to 2016. Graphical data obtained from device interrogations were retrospectively converted to numerical data. The activity level averaged over a month from a week postimplantation was used as baseline. Subsequent weekly average activity levels (SALs) were standardized to this baseline. SAL below 59.4% was used as a threshold to group patients. All-cause mortality and death/heart failure were the primary end-points of this study. RESULTS: Fifty-six patients died in this study. On average, they experienced a 50% decline in SAL prior to death. Patients (n = 129) who dropped their SAL below threshold were more likely to be older, male, diabetic, and have more symptomatic heart failure. They also had a significantly increased risk of heart failure/death (hazard ratio [HR] 3.6, 95% confidence interval [95% CI] 2.3-5.8, P < .0001) or death (HR 4.2, 95% CI 2.2-7.7, P < .0001) compared to those who had sustained activity levels. Lower baseline activity level was also associated with significantly increased risk of heart failure/death and death. CONCLUSION: Significant decline in device-derived activity level and low baseline activity level are associated with increased mortality and heart failure in patients with an ICD for primary prevention.

True bipolar or extended bipolar left ventricular pacing is associated with better survival in cardiac resynchronization therapy patients.

BACKGROUND: Limited studies are available on the clinical significance of left ventricular (LV) lead polarity in patients undergoing cardiac resynchronization therapy (CRT), with a recent study suggesting better outcomes with LV true bipolar pacing. OBJECTIVE: We aimed to determine whether true bipolar LV pacing is associated with reduced mortality in a large, real-life CRT cohort, followed by remote monitoring. METHODS: We analyzed de-identified device data from CRT patients followed by the Boston Scientific LATITUDE remote monitoring database system. Patients with LV bipolar leads paced between the LV ring and LV tip were identified as true bipolar and those with LV bipolar leads paced between LV tip or LV ring and right ventricular (RV) coil were identified as extended bipolar. Patients with unipolar leads were identified as unipolar. RESULTS: Of the 59 046 patients included in the study, 2927 had unipolar pacing, 34 390 had extended bipolar pacing, and 21 729 had true bipolar pacing. LV true bipolar pacing was associated with a significant 30% lower risk of all-cause mortality as compared to unipolar pacing (hazards ratio [HR] = 0.70, 95% CI: 0.62-0.79, P < .001), after adjustment for age, gender, LV lead impedance, LV pacing threshold, and BIV pacing percentage <95%. Extended bipolar LV pacing was also associated with 24% lower risk of all-cause mortality when compared to unipolar LV pacing (HR = 0.76, 95% CI: 0.68-0.85; P < .001). However, there were no differences in outcomes between true bipolar and extended bipolar LV pacing (HR = 0.97, 95% CI: 0.93-1.01; P = .198). CONCLUSION: True bipolar or extended bipolar LV pacing is associated with a lower risk of mortality in CRT patients as compared to unipolar LV pacing.

Stroke and thromboembolism prevention in atrial fibrillation.

Prevention of stroke and systemic thromboembolism remains the cornerstone for management of atrial fibrillation (AF) and flutter. Multiple risk assessment models for stroke and systemic thromboembolism are currently available. The score, with its known limitations, remains as the recommended risk stratification tool in most major guidelines. Once at-risk patients are identified, vitamin K antagonists (VKAs) and, more recently, direct oral anticoagulants (DOACs) are the primary medical therapy for stroke prevention. In those with contraindication for long-term anticoagulation, left atrial appendage occluding devices are developing as a possible alternative therapy. Some controversy exists regarding anticoagulation management for cardioversion of acute AF (<48 hours); however, systemic anticoagulation precardioversion and postcardioversion is recommended for those with longer duration of AF. Anticoagulation management peri-AF ablation is also evolving. Uninterrupted VKA and DOAC therapy has been shown to reduce perioperative thromboembolic risk with no significant escalation in major bleeding. Currently, under investigation is a minimally interrupted approach to anticoagulation with DOACs periablation. Questions remain, especially regarding the delivery of anticoagulation care and integration of wearable rhythm monitors in AF management.

Thromboembolic prophylaxis protocol with warfarin after radiofrequency catheter ablation of infarct-related ventricular tachycardia.

INTRODUCTION: Ablation in the left ventricle (LV) is associated with a risk of thromboembolism. There are limited data on the use of specific thromboembolic prophylaxis strategies postablation. We aimed to evaluate a thromboembolic prophylaxis protocol after ventricular tachycardia (VT) ablation. METHODS AND RESULTS: The index procedures of 217 patients undergoing ablation for infarct-related VT with open irrigated-tip catheters were included. Patients with large LV endocardial ablation area (>3 cm between ablation lesions) were started on low-dose, slowly escalating unfractionated heparin (UFH) infusion 8 hours after access hemostasis, followed by 3 months of anticoagulation. Patients with less extensive ablation were treated only with antiplatelet agents postablation. Postablation bridging anticoagulation was used in 181 (83%) patients. Of them, 11 (6%) patients experienced bleeding events (1 required endovascular intervention) and 1 (0.6%) experienced lower extremity arterial embolism requiring vascular surgery. Systemic anticoagulation was prescribed in 190 (89%) of 214 patients discharged from the hospital (warfarin in 98%), while the rest received single- or dual-antiplatelet therapy alone. Patients treated with an anticoagulant had significantly longer radiofrequency time compared to patients treated with antiplatelet agents only. One (0.5%) of the patients treated with oral anticoagulation experienced major bleeding 2 weeks postablation. No thromboembolic events were documented in either the anticoagulation or the "antiplatelet only" group postdischarge. CONCLUSION: A slowly escalating bridging regimen of UFH, followed by 3 months of oral anticoagulation, is associated with low thromboembolic and bleeding risks after infarct-related VT ablation. In the absence of extensive ablation, antiplatelet therapy alone is reasonable.

Predictive value of device-derived activity level for short-term outcomes in MADIT-CRT.

BACKGROUND: There are limited data on the prognostic importance of declining activity level in patients with heart failure. OBJECTIVE: We aimed to assess the association of reduced activity level with adverse cardiovascular outcomes in the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT). METHODS: Final device interrogations from patients enrolled in the MADIT-CRT with cardiac resynchronization devices capable of recording percent daily activity level were assessed. To determine temporal change, standardized activity levels (SALs) comparing each week to the monthly activity 3 months prior were obtained. Death, heart failure events (HFEs)/death, and ventricular tachyarrhythmias (VTAs)/death were the primary end points of this study. RESULTS: The average absolute activity level and SAL of the final week prior to death or end of study were significantly lower in patients who died compared with those in patients who did not. The total cohort (N = 1008) was further randomized into 2 subgroups to identify (group 1) and validate an optimal threshold (group 2). Patients with >40% reduced SAL had a significantly increased 77-day short-term cumulative incidence of death (P = .0006), HFE/death (P < .0001), or VTA/death (P = .0248). After adjustment for clinical covariates, these patients remained at an increased risk for death (hazard ratio [HR], 2.7; 95% confidence interval [CI], 1.5-4.9; P = .001), HFE/death (HR, 2.7; 95% CI, 1.8-3.9; P ≤ .001) and VTA/death (HR, 1.9; 95% CI, 1.31-2.6; P = .001). A decline in SAL following a nonfatal VTA and HFE was also associated with an increased probability of death. CONCLUSIONS: Decline in activity level is a short-term predictor for adverse cardiovascular events in patients with mild to moderate heart failure undergoing cardiac resynchronization.

Bipolar left ventricular pacing is associated with significant reduction in heart failure or death in CRT-D patients with LBBB.

BACKGROUND: There are limited data on the significance of left ventricular (LV) lead pacing polarity to predict clinical outcomes. OBJECTIVES: We aimed to determine the association between the LV lead pacing polarity for heart failure (HF) or death and ventricular tachyarrhythmias (VTA) in patients enrolled in MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy), receiving a cardiac resynchronization therapy device with implanted cardioverter-defibrillator (CRT-D). METHODS: We retrospectively analyzed LV pacing polarity. Patients with LV bipolar leads paced between LV ring and LV tip were identified as True Bipolar, while those with LV bipolar leads paced between LV tip or LV ring and right ventricular coil or unipolar leads were identified as Unipolar/Extended Bipolar. Kaplan-Meier survival analyses and multivariate Cox proportional hazards regression models were used. RESULTS: Of the 969 patients, 421 had True Bipolar pacing while the remainder (n = 548) had Unipolar/Extended Bipolar pacing. Among patients with left bundle branch block (LBBB), True Bipolar pacing was associated with lower cumulative incidence of death (P = .022) and HF/death (P = .046) compared to those with Unipolar/Extended Bipolar LV pacing. After adjustment for clinical covariates, bipolar LV pacing in LBBB patients was associated with 54% lower risk for death (HR: 0.46; 95% CI: 0.24-0.88; P = .020) and 32% lower risk for HF/death (HR: 0.68; 95% CI: 0.46-1.00; P = .048) compared to Unipolar/Extended Bipolar LV pacing, but not in those with non-LBBB. No association was seen with risk of ventricular tachyarrhythmia. CONCLUSION: True Bipolar LV pacing configuration is associated with a significantly lower risk of HF/death and all-cause mortality in CRT-D patients with LBBB.

The new lipid guidelines: what do primary care clinicians think?

BACKGROUND: Little is known about the opinions of primary care clinicians regarding the newly released 2013 American College of Cardiology/American Heart Association (ACC/AHA) Guidelines for the Prevention of Primary and Secondary Atherosclerotic Disease. This survey was created to assess the awareness, attitudes, and practices of primary care clinicians on adoption of the new guidelines and to explore obstacles to implementation and suggestions for improving shared decision-making. METHODS: Six hundred practicing clinicians within the San Francisco Bay Area Collaborative Research Network were invited to participate in this cross-sectional, Internet-based pilot survey of primary care clinicians. These survey data were collected in March 2014, approximately 4 months after the release of the new guidelines and 1 month after the release of the ACC/AHA risk estimator application. RESULTS: One hundred eighty-three clinicians responded to the survey. Of those respondents, 176 (96%) were aware of the guidelines. The majority (64%) reported implementing the new guidelines with at least some of their patients, while a minority (25%) reported adopting the guidelines for many of their patients. Disagreeing with the guidelines was the main hindrance to adoption. CONCLUSIONS: While many primary care clinicians are aware of the new guidelines, a substantial proportion has yet to implement them into their clinical practice, and obstacles remain for full adoption. Further understanding of clinicians' views, opinions, and needs is necessary to optimize the approach to lipid management and ensure integration into current practice.

Endothelial cells derived from human iPSCS increase capillary density and improve perfusion in a mouse model of peripheral arterial disease.

OBJECTIVE: Stem cell therapy for angiogenesis and vascular regeneration has been investigated using adult or embryonic stem cells. In the present study, we investigated the potential of endothelial cells (ECs) derived from human induced pluripotent stem cells (hiPSCs) to promote the perfusion of ischemic tissue in a murine model of peripheral arterial disease. METHODS AND RESULTS: Endothelial differentiation was initiated by culturing hiPSCs for 14 days in differentiation media supplemented with BMP-4 and vascular endothelial growth factor. The hiPSC-ECs exhibited endothelial characteristics by forming capillary-like structures in matrigel and incorporating acetylated-LDL. They stained positively for EC markers such as KDR, CD31, CD144, and eNOS. In vitro exposure of hiPSC-ECs to hypoxia resulted in increased expression of various angiogenic related cytokines and growth factors. hiPSC-ECs were stably transduced with a double fusion construct encoded by the ubiquitin promoter, firefly luciferase for bioluminescence imaging and green fluorescence protein for fluorescent detection. The hiPSC-ECs (5×10(5)) were delivered by intramuscular injection into the ischemic hindlimb of SCID mice at day 0 and again on day 7 after femoral artery ligation (n=8). Bioluminescence imaging showed that hiPSC-ECs survived in the ischemic limb for at least 2 weeks. In addition, laser Doppler imaging showed that the ratio of blood perfusion was increased by hiPSC-EC treatment by comparison to the saline-treated group (0.58±0.12 versus 0.44±0.04; P=0.005). The total number of capillaries in the ischemic limb of mice receiving hiPSC-EC injections was greater than those in the saline-treated group (1284±155 versus 797±206 capillaries/mm(2)) (P<0.002). CONCLUSION: This study is a first step toward development of a regenerative strategy for peripheral arterial disease based on the use of ECs derived from hiPSCs.

Mfge8 diminishes the severity of tissue fibrosis in mice by binding and targeting collagen for uptake by macrophages.

Milk fat globule epidermal growth factor 8 (Mfge8) is a soluble glycoprotein known to regulate inflammation and immunity by mediating apoptotic cell clearance. Since fibrosis can occur as a result of exaggerated apoptosis and inflammation, we set out to investigate the hypothesis that Mfge8 might negatively regulate tissue fibrosis. We report here that Mfge8 does decrease the severity of tissue fibrosis in a mouse model of pulmonary fibrosis; however, it does so not through effects on inflammation and apoptotic cell clearance, but by binding and targeting collagen for cellular uptake through its discoidin domains. Initial analysis revealed that Mfge8-/- mice exhibited enhanced pulmonary fibrosis after bleomycin-induced lung injury. However, they did not have increased inflammation or impaired apoptotic cell clearance after lung injury compared with Mfge8+/+ mice; rather, they had a defect in collagen turnover. Further experiments indicated that Mfge8 directly bound collagen and that Mfge8-/- macrophages exhibited defective collagen uptake that could be rescued by recombinant Mfge8 containing at least one discoidin domain. These data demonstrate a critical role for Mfge8 in decreasing the severity of murine tissue fibrosis by facilitating the removal of accumulated collagen.