Safety of catheter ablation in patients with recently implanted cardiac implantable electronic device: A 5-year experience.

INTRODUCTION: Catheter ablation (CA) can interfere with cardiac implantable electronic device (CIED) function. The safety of CA in the 1st year after CIED implantation/lead revision is uncertain. METHODS: This single center, retrospective cohort included patients who underwent CA between 2012 and 2017 and had a CIED implant/lead revision within the preceding year. We assessed the frequency of device/lead malfunctions in this population. RESULTS: We identified 1810 CAs in patients between 2012 and 2017, with 170 CAs in 163 patients within a year of a CIED implant/lead revision. Mean age 68 ± 12 years (68% men). Time between the CIED procedure and CA was 158 ± 99 days. The CA procedures included AF ablation (n = 57, 34%), AV node ablation (n = 40, 24%), SVT ablation (n = 37, 22%), and PVC/VT ablations (n = 36, 21%). The cumulative frequency of lead dislodgement, significant CIED dysfunction, and/or CIED-related infection following CA was (n = 1/170, 0.6%). There was a single atrial lead dislodgement (0.6%). There were no instances of power-on-reset or CIED-related infection. Following CA, there was no significant difference in RA or RV lead sensing (p = 0.52 and 0.84 respectively) or thresholds (p = 0.94 and 0.17 respectively). The RA impedance slightly decreased post-CA from 474 ± 80 Ohms to 460 ± 73 Ohms (p = 0.002), as did the RV impedance (from 515 ± 111 Ohms to 497 ± 98 Ohms, p < 0.0001). CONCLUSIONS: CA can be performed within 1 year following CIED implantation/lead revision with a low risk of CIED/lead malfunction or lead dislodgement. The ideal time to perform CA after a CIED remains uncertain.

Cardiac resynchronization therapy for pacing induced cardiomyopathy: Role of baseline right ventricular pacing burden.

BACKGROUND: Cardiac resynchronization therapy (CRT) is indicated for patients with heart failure with reduced left ventricular ejection fraction (LVEF) and chronic right ventricular (RV) pacing burden ≥40% (pacing-induced cardiomyopathy, PICM). It is uncertain whether baseline RV pacing burden impacts response to CRT. METHODS: We conducted a retrospective study of all CRT upgrades for PICM at our hospital from January 2017 to December 2018. Univariate and multivariable-adjusted changes in LVEF, and echocardiographic response (≥10% improvement in LVEF) at 3-12 months post-CRT upgrade were compared in those with RV pacing burden ≥90% versus <90%. RESULTS: We included 75 patients (age 74 ± 11 years, 71% male) who underwent CRT upgrade for PICM. The baseline RV pacing burden was ≥90% in 56 patients (median 99% [IQR 98%-99%]), and <90% in 19 patients (median 79% [IQR 73%-87%]). Improvement in LVEF was greater in those with baseline RV pacing burden ≥90% versus <90% (15.7 ± 9.3% vs. 7.5 ± 9.6%, p = .003). Baseline RV pacing burden ≥90% was a strong predictor of an improvement in LVEF ≥10% after CRT upgrade both in univariate and multivariate-adjusted models (p = .005 and .02, respectively). CONCLUSION: A higher baseline RV pacing burden predicts a greater improvement in LVEF after CRT upgrade for PICM.

Multicenter assessment of the outcomes of subcutaneous ICD implantation in patients with prior or future sternotomy.

BACKGROUND: The subcutaneous ICD (S-ICD) is a viable alternative to transvenous ICD and avoids intravascular complications in patients without a pacing indication. The outcomes of S-ICD implantation are uncertain in patients with prior sternotomy. OBJECTIVE: We aim to compare the implant techniques and outcomes with S-ICD implantation in patients with and without prior sternotomy. METHODS: Multicenter retrospective cohort study including adult patients with an S-ICD implanted between January 2014 and June 2020. Outcomes were compared between patients with and without prior sternotomy. RESULTS: Among the 212 patients (49 ± 15 years old, 43% women, BMI 30 ± 8 kg/m2 , 68% primary prevention, 30% ischemic cardiomyopathy, LVEF median 30% IQR 25%-45%) who underwent S-ICD implantation, 47 (22%) had a prior sternotomy. There was no difference in the sensing vector (57% vs. 53% primary, p = 0.55), laterality of the S-ICD lead to the sternum (94% vs. 96% leftward, p = 0.54), or the defibrillation threshold (65 ± 1.4 J vs. 65 ± 0.8 J, p = 0.76) with versus without prior sternotomy. The frequency of 30-day complications was similar with and without prior sternotomy (n = 3/47 vs. n = 15/165, 6% vs. 9%, p = 0.56). Over a median follow-up of 28 months (IQR 10-49 months), the frequency of inappropriate shocks was similar between those with and without prior sternotomy (n = 3/47 and n = 16/165, 6% vs. 10%, p = 0.58). CONCLUSION: Implantation of an S-ICD in patients with prior sternotomy is safe with a similar risk of 30-day complications and inappropriate ICD shocks as patients without prior sternotomy.

Differences in outcomes among patients with atrial fibrillation undergoing catheter ablation with versus without intracardiac echocardiography.

BACKGROUND: Intracardiac echocardiography (ICE) use can lead to early detection of periprocedural complications and may improve patient outcomes by providing real-time visualization of catheter location and the treatment area during cardiac ablation (CA) for atrial fibrillation (AF). OBJECTIVE: Examine complications and 12-month healthcare use among patients with AF undergoing CA with versus without ICE use during the procedure in a real-world setting. METHODS: The 2015-2020 IBM MarketScan® Database was used to identify non-elderly adults (age 18-64 years) undergoing CA for AF. Patients were classified into ICE/non-ICE groups based on the presence or absence of ICE procedure codes. Patients in each group were matched on study covariates using propensity scores. Peri-procedural complications, 12-month cardiovascular (CV) or AF-related inpatient admission, repeat CA, and cardioversion were compared using a Cox proportional hazard model. RESULTS: 1371 patients were identified in each study cohort (ICE and non-ICE) after propensity matching. Patients who had CA with ICE had a significantly lower rate of complications than those without (2.9% vs. 5.8%; p < .001). The risk of complications was 50% lower with ICE use (hazard ratio [HR] 0.50; 95% confidence interval [CI] 0.34-0.72). For assessment of 12-month healthcare utilization, 1250 patients were identified in each cohort after propensity matching. ICE use was associated with a 36% lower risk of 12-month repeat ablation (HR 0.64; 95% CI 0.49-0.83). No differences in CV- or AF-related inpatient admission and cardioversion were observed. CONCLUSION: Among patients with AF, the use of ICE during an ablation procedure was associated with lower incidence of complications and repeat ablation.

Emerging Implantable-Device Technology for Patients at the Intersection of Electrophysiology and Heart Failure Interdisciplinary Care.

Cardiac implantable electronic devices, including implantable cardioverter-defibrillators and therapy, are part of guideline-indicated treatment for a subset of patients with heart failure with reduced ejection fraction. Current technological advancements in cardiac implantable electronic devices have allowed the detection of specific physiological parameters that are used to forecast clinical decompensation through algorithmic, multiparameter remote monitoring. Other recent emerging technologies, including cardiac contractility modulation and baroreflex activation therapy, may provide symptomatic or physiological benefits in patients without indications for cardiac resynchronization. Our goal in this state-of-the-art review is to describe the new commercially available technologies, their purported mechanisms of action, and the evidence surrounding their clinical roles, limitations and future directions. Finally, we underline the need for standardized workflow and close interdisciplinary management of this population to ensure the delivery of high-quality care.

UltraSound Axillary Vein Access (USAA): Learning curve and randomized comparison to traditional venous access for cardiac device implantation.

BACKGROUND: Many techniques exist for venous access (VA) during cardiac implantable electronic device (CIED) implantation. OBJECTIVE: We sought to evaluate the learning curve with ultrasound (US) guided axillary vein access (USAA). METHODS: Single-center prospective randomized controlled trial of patients undergoing CIED implantation. Patients were randomized in a 2:1 fashion to USAA versus conventional VA techniques. The primary outcomes were the success rates, VA times and 30-day complication rates. RESULTS: The study included 100 patients (age 68 ± 14 years, BMI 27 ± 4 kg/m2 ). USAA was successful in 66/70 implants (94%). Initial attempts at conventional VA included 47% axillary (n = 14), 30% (n = 9) cephalic, and 23% (n = 7) subclavian. The median access time was longer for USAA than conventional access (8.3 IQR 4.2-15.3 min vs. 5.2 IQR 3.4-8.6 min, p = .009). Among the five inexperienced USAA implanters, there was a significant improvement in median access time from first to last tertile of USAA implants (17.0 IQR 7.0-21.0 min to 8.6 IQR 4.5-10.8 min, p = .038). The experienced USAA implanter had similar access times with USAA compared with conventional access (4.0 IQR 3.3-4.7 min vs. 5.2 IQR 3.4-8.6 min, p = .15). Venograms were less common with USAA than conventional access (2% vs. 33%, p < .0001). The 30-day complication rate was similar with USAA (n = 4/70, 6%) versus conventional (n = 3/30, 10%, p = .44). CONCLUSION: Although the success rate with USAA was high, there was a significant learning curve. Once experienced with the USAA technique, there is the potential for reduced complications without adding to the procedure duration.

Impact of ultra-conservative ICD programming in patients with LVADs: Avoiding potentially unnecessary tachy-therapies.

BACKGROUND: Patients with left ventricular assist devices (LVAD) often tolerate ventricular arrhythmias (VA). We aim to assess the frequency and outcomes of ICD therapies averted by ultraconservative ICD programming (UCP) in LVAD patients. METHODS: This single center, retrospective cohort study included patients with LVADs and ICDs implanted from 2015 to 2019 that had UCP. The aim for UCP was to maximally delay VA treatments and maximize anti-tachycardia pacing (ATP) prior to ICD shocks. VA events were reviewed after UCP and evaluated under prior conservative programming to assess for potentially averted events (that would have resulted in either ATP or defibrillation with prior programming). RESULTS: Fifty patients were included in the study with follow-up of median 16 ± 10.2 months after UCP. The median time from LVAD implantation to reprogramming was 7 days (IQR 5-9 days). Fourteen patients (28%) had potentially averted VA events that would have been treated with their prior ICD programming (82 total events, median two events per patient, IQR 1-10 events). Treated VA events occurred in 15 patients (30%). Eleven of the 14 patients with potentially averted VAs had treated events as well. Only one patient reported definitive symptoms of self-limited "dizziness" during a potentially averted event that did not result in hospitalization. No patients died of complications from or needed emergent care/hospitalization due a potentially averted VA. CONCLUSIONS: UCP in LVAD patients likely prevented unnecessary VA treatments in many patients with minimal reported symptoms during these potentially averted events. Prospective studies are necessary to confirm these findings.

Ultrasound guided axillary vein access: An alternative approach to venous access for cardiac device implantation.

INTRODUCTION: Ultrasound guided axillary vein access (UGAVA) is an emerging approach for cardiac implantable electronic device (CIED) implantation not widely utilized. METHODS AND RESULTS: This is a retrospective, age and sex-matched cohort study of CIED implantation from January 2017 to July 2019 comparing UGAVA before incision to venous access obtained after incision without ultrasound (conventional). The study population included 561 patients (187 with attempted UGAVA, 68 ± 13 years old, 43% women, body mass index (BMI) 30 ± 8 kg/m2 , 15% right-sided, 43% implantable cardioverter-defibrillator, 15% upgrades). UGAVA was successful in 178/187 patients (95%). In nine patients where UGAVA was abandoned, the vein was too deep for access before incision. BMI was higher in abandoned patients than successful UGAVA (38 ± 6 vs. 28 ± 6 kg/m2 , p < .0001). Median time from local anesthetic to completion of UGAVA was 7 min (interquartile range [IQR]: 4-10) and median procedure time 61 min (IQR: 50-92). UGAVA changed implant laterality in two patients (avoiding an extra incision in both) and could have prevented unnecessary incision in four conventional patients. Excluding device upgrades, there was reduced fluoroscopy time in UGAVA versus conventional (4 vs. 6 min; IQR: 2-5 vs. 4-9; p < .001). Thirty-day complications were similar in UGAVA versus conventional (n = 7 vs. 26, 4 vs. 7%; p = .13, p = .41 adjusting for upgrades), partly driven by a trend towards reduced pneumothorax (n = 0 vs. 3, 0 vs. 1%; p = .22). CONCLUSIONS: UGAVA is a safe approach for CIED implantation and helps prevent an extra incision if a barrier is identified changing laterality preincision.

Comparison of peri-procedural anticoagulation with rivaroxaban and apixaban during radiofrequency ablation of atrial fibrillation.

INTRODUCTION: Prospective studies on rivaroxaban and apixaban have shown the safety and efficacy of direct anticoagulation agents (DOAC)s used peri-procedurally during radiofrequency ablation (RFA) of atrial fibrillation (AF). Studies comparing the two agents have not been performed. METHODS: Consecutive patients from a prospective registry who underwent RFA of AF between April 2012 and March 2015 and were on apixaban or rivaroxaban were studied. Clinical variables and outcomes were noted. RESULTS: There were a total of 358 patients (n = 56 on apixaban and n = 302 on rivaroxaban). There were no differences in baseline characteristics between both groups. The last dose of rivaroxaban was administered the night before the procedure in 96% of patients. In patients on apixaban, 48% of patients whose procedure was in the afternoon took the medication on the morning of the procedure. TIA/CVA occurred in 2 patients (0.6%) in rivaroxaban group with none in apixaban group (p = 0.4). There was no difference in the rate of pericardial effusion between apixaban and rivaroxaban groups [1.7% vs 0.6% (p = 0.4)]. Five percent of patients in both groups had groin complications (p = 0.9). In apixaban group, all groin complications were small hematomas except one patient who had a pseudoaneurysm (1.6%). One pseudo-aneurysm, 1 fistula and 3 large hematomas were noted in patients on rivaroxaban (1.7%) with the rest being small hematomas. DOACs were restarted post procedure typically 4 h post hemostasis. CONCLUSIONS: Peri-procedural uninterrupted use of apixaban and rivaroxaban during AF RFA is safe and there are no major differences between both groups.

Perioperative hematoma with subcutaneous ICD implantation: Impact of anticoagulation and antiplatelet therapies.

BACKGROUND: The safety of perioperative anticoagulation (AC) and antiplatelet (AP) therapy with subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation is unknown. The purpose of this study was to identify the risk factors associated with hematoma complicating S-ICD implantation. METHODS: Records were retrospectively reviewed from 200 consecutive patients undergoing S-ICD implantation at two academic medical centers. A hematoma was defined as a device site blood accumulation requiring surgical evacuation, extended hospital stay, or transfusion. RESULTS: Among 200 patients undergoing S-ICD implantation (age 49 ± 17 years, 67% men), 10 patients (5%) had a hematoma, which required evacuation in six patients (3%). Warfarin was bridged or uninterrupted in 12 and 13 patients, respectively (6% and 6.5%). Four of 12 patients with warfarin and bridging AC (33%) and two of 13 patients with uninterrupted warfarin (15%) developed a hematoma. Neither of the two patients with uninterrupted DOAC had a hematoma. No patients on interrupted AC without bridging (n = 26, 13 with warfarin, 13 with DOAC) developed a hematoma. A hematoma was also more likely with the use of clopidogrel (n = 4/10 vs 10/190, 40% vs 5.3%, P < 0.0001) in combination with aspirin in 12/14 patients. Any bridging AC (odds ratio [OR] 10.3, 1.8-60.8, P = 0.01), clopidogrel (OR 10.0, 1.7-57.7, P = 0.01), and uninterrupted warfarin without bridging (OR 11.1, 1.7-74.3, P = 0.013) were independently associated with hematoma formation. CONCLUSION: AC and/or AP therapy with clopidogrel appears to increase the risk for hematoma following S-ICD implantation. Interruption of AC without bridging should be considered when it is an acceptable risk to hold AC.

Defibrillation thresholds with right pectoral implantable cardioverter defibrillators and impact of waveform tuning (the Tilt and Tune trial).

AIMS: Assess defibrillation thresholds (DFTs) with right active pectoral implantable cardioverter defibrillator (RICDs). Defibrillation thresholds in patients receiving RICDs are regarded as 'high' and potentially improved by waveform optimization (tuning). However, this has not been systematically tested. METHODS AND RESULTS: Patients receiving RICDs [Single chamber (VVI) = 16, DDD = 32, cardiac resynchronization therapy (CRT) = 43] were randomized to either 50/50% fixed tilt (FT) or tuned waveform (3.5 ms time constant based). Defibrillation threshold was tested with a binary search protocol in single coil anodal configuration. Then RICDs were compared with left-sided placements. Baseline patient characteristics in FT (n = 54) and tuned (n = 37) were similar (65 ± 14 years, 71% male, Left ventricular ejection fraction 31 ± 13%; and proportions VVI/DDD/Cardiac resynchronization therapy defibrillator). Tuning reduced Phase 1 by 15% and Phase 2 by 45%. For FT vs. tuned: high voltage impedance was 61.9 ± 13.2 vs. 64.5 ± 12.7 Ω (P = 0.33) and mean DFT 14.2 ± 8.8 vs. 14.9 ± 9.2 J (P = 0.8). When high voltage impedance was >62 Ω (mean 73.6 ± 8.6 Ω), DFT was identical [FT 13.0 ± 7.9 J vs. tuned 12.0 ± 5.9 J (P= 0.7)]. Defibrillation thresholds exceeded 20 J (600 V) in >20% of patients [FT 11/54 (20.4%) vs. tuned 12/37 (32%) patients]. Defibrillation threshold with RICD was greater and exhibited wider dispersion compared with left ICDs (n = 54) under similar conditions. CONCLUSION: This first randomized trial investigating DFTs with right ICDs confirms relatively higher DFTs with RICDs than reported for left pectoral ICDs. However, DFTs were generally unaffected by 3.5 ms time constant-based waveform tuning compared with a 50% tilt waveform. Implant testing may be preferred with RICDs. CLINICAL TRIAL NUMBER: NCT00873691.

Under-Utilization of Implantable Cardioverter Defibrillators in Patients with Heart Failure - The Current State of Sudden Cardiac Death Prophylaxis.

BACKGROUND: Despite ACC/AHA guidelines indicating implantable cardioverter defibrillator (ICD) as class I therapy for primary prevention of sudden cardiac death in patients with EF≤35%, ICD utilization rates in real world practice have been low. OBJECTIVE: To determine the rate of ICD implantation at a tertiary care academic center and to assess the reasons for under-utilization of the same. METHODS: Review of a prospectively collected database which included all patients diagnosed with an EF≤35% was performed to assess the rate of ICD implantation and mortality. Reasons for non-implantation of ICD were then assessed from detailed chart review. RESULTS: A total of 707 patients (age 69.4 ± 14.1 years) with mean EF of 26±7% were analyzed. Only 28% (200/707) of patients had ICDs implanted. Mortality was lower in the group with ICD (25% vs 37%, p=0.004). When patients who either died or were lost to follow-up prior to 2005 were excluded, ICD utilization rate was still low at 37.6%. The most common reason for non-implantation of ICD was physicians not discussing this option with their patients. Patient refusal was the second most common reason. CONCLUSIONS: ICD Implantation rates for primary prevention of SCD in patients with EF≤35% is low. Physician and patient education should be addressed to improve the utilization rates.

Case Series and Review of Literature for Superior Vena Cava Injury During Laser Lead Extraction.

Transvenous laser lead extraction poses a risk of major complications (0.19%-1.8%), notably injury to the superior vena cava (SVC) in 0.19% to 0.96% of cases. Various factors contribute to SVC injury, which can be categorized as patient-related (such as female gender, low body mass index, diabetes, renal problems, anemia, and reduced ejection fraction), device-related (including the number, dwell time, and type of leads), or procedural-related (such as reason for extraction, venous obstructions, and bilateral lead placements).

Ventricular Arrhythmia in Cancer Patients: Mechanisms, Treatment Strategies and Future Avenues.

Cardiovascular disease and cancer are the leading causes of morbidity and mortality in the US. Despite the significant progress made in cancer treatment leading to improved prognosis and survival, ventricular arrhythmias (VA) remain a known cardiovascular complication either exacerbated or induced by the direct and indirect effects of both traditional and novel cancer treatments. Although interruption of cancer treatment because of VA is rarely required, knowledge surrounding this issue is essential for optimising the overall care of patients with cancer. The mechanisms of cancer-therapeutic-induced VA are poorly understood. This review will discuss the ventricular conduction (QRS) and repolarisation abnormalities (QTc prolongation), and VAs associated with cancer therapies, as well as existing strategies for the identification, prevention and management of cancer-treatment-induced VAs.

Sudden cardiac death in women.

Women are at lower risk for development of sudden cardiac death (SCD) as compared with men. Women with SCD tend to have less structural heart disease and preserved left ventricular systolic function. Coronary artery disease (CAD) is the most common predictor of SCD in women, as it is in men. However, women with SCD are less likely to have underlying CAD than men, suggesting the need to identify risk factors other than CAD or systolic dysfunction for its prediction in women. SCD risk factors in women include heart failure with preserved left ventricular systolic function, abnormal sympathetic uptake as assessed by meta-iodobenzylguanidine uptake, depression, and/or use of antidepressants. This article reviews SCD in women and discusses areas for future research.

Intracardiac echo-guided radiofrequency catheter ablation of atrial fibrillation in patients with atrial septal defect or patent foramen ovale repair: a feasibility, safety, and efficacy study.

UNLABELLED: Intracardiac Echo-Guided Radiofrequency Catheter. INTRODUCTION: Patients with atrial septal defect (ASD) are at higher risk for atrial fibrillation (AF) even after repair. Transseptal access in these patients is perceived to be difficult. We describe the feasibility, safety, and efficacy of pulmonary vein antral isolation (PVAI) in these patients. METHOD: We prospectively compared post-ASD/patent foramen ovale (PFO) repair patients (group I, n = 45) with age-gender-AF type matched controls (group II, n = 45). All the patients underwent PVAI through a double transseptal puncture with a roving circular mapping catheter technique guided by intracardiac echocardiography (ICE). The short-term (3 months) and long-term (12 month) failure rates were assessed. RESULTS: In group I, 23 (51%) had percutaneous closure devices and 22 (49%) had a surgical closure. There was no significant difference between group I and II in the baseline characteristics. Intracardiac echo-guided double transseptal access was obtained in 98% of patients in group I and in 100% of patients in group II. PVAI was performed in all patients, with right atrial flutter ablation in 7 patients in group I and in 4 patients in group II. Over a mean follow-up of 15 +/- 4 months, group I had higher short-term (18% vs 13%, P = 0.77) and long-term recurrence (24% vs 18%, P = 0.6) than group II. There was no significant difference in the perioperative complications between the two groups. Echocardiography at 3 months showed interatrial communication in 2 patients in group I and 1 patient in group II, which resolved at 12 months. CONCLUSION: Percutaneous AF ablation using double transseptal access is feasible, safe, and efficacious in patients with ASD and PFO repairs.

Use of Oral Steroid and its Effects on Atrial Fibrillation Recurrence and Inflammatory Cytokines Post Ablation - The Steroid AF Study.

BACKGROUND: Use of corticosteroids before and after atrial fibrillation (AF) ablation can decrease acute inflammation and reduce AF recurrence. PURPOSE: To assess the efficacy of oral prednisone in improving the outcomes of pulmonary vein isolation with radiofrequency ablation and its effect on inflammatory cytokine. METHODS: A total of 60 patients with paroxysmal AF undergoing radiofrequency ablation were randomized (1:1) to receive either 3 doses of 60 mg daily of oral prednisone or a placebo. Inflammatory cytokine levels (TNF-α, IL-1, IL6, IL-8) were measured at baseline, prior to ablation, immediately after ablation, and 24 hours post ablation. Patients underwent 30 day event monitoring at 3 months, 6 months and 12 months post procedure. RESULTS: Immediate post ablation levels of inflammatory cytokines were lower in the steroid group when compared to the placebo group; IL-6: 9.0 ±7 vs 15.8 ±13 p=0.031; IL-8: 10.5 ±9 vs 15.3 ±8; p=0.047 respectively. Acute PV reconnection rates during the procedure (7/23% vs 10/36%; p = 0.39), and RF ablation time (51±13 vs 56±11 min, p = 0.11) trended to be lower in the placebo group than the steroid group. There was no difference in the incidence of early recurrence of AF during the blanking period and freedom from AF off AAD at 12 months between both groups (5/17% vs 8/27%; p = 0.347 and 21/70% vs 18/60%; p=0.417 in placebo and steroid groups respectively). CONCLUSION: Although oral corticosteroids have significant effect in lowering certain cytokines, it did not impact the clinical outcomes of AF ablation.

Practice variation in the re-initiation of dofetilide: An observational study.

BACKGROUND: Dofetilide is a class III antiarrhythmic drug that has been reported to be safe and efficacious in the treatment of atrial dysrhythmias with a known initial risk of QT prolongation and torsades de pointes (TdP). As a result, the Federal Drug Administration (FDA) mandated in-hospital dofetilide initiation and adherence to a common dosing protocol. However, there is a lack of clarity on how to manage dofetilide re-initiation. METHODS: An observational survey was performed including 347 cardiologists in the United States and worldwide to evaluate the deviations from approved manufacturer's protocol during dofetilide initiation and re-initiation among practicing cardiologists. RESULTS: Most practicing cardiologists were cautious about outpatient dofetilide use and adhered to the manufacturer's in-patient dofetilide protocol during de-novo initiation and reported low incidence of TdP in clinical practice. There were substantial differences among practicing cardiologists with deviation from the manufacturer's protocol during re-initiation of dofetilide. About 21% cardiologists always admitted patients to the hospital while 37% admitted patients <10% of the time for dofetilide re-initiation. Only 4% reported major adverse events with outpatient dofetilide re-initiation. There was also wide variation regarding monitoring of electrolytes and QT interval as an outpatient with dofetilide. CONCLUSION: There is significant practice pattern variation in the use of dofetilide for the management of AF. This degree of variation noted is concerning and is a reflection of the current lack of substantial clinical evidence in the re-initiation dofetilide protocol to help direct the provider.

Autocrine regulation of myocyte Cx43 expression by VEGF.

Cardiac myocytes can rapidly adjust their expression of gap junction channel proteins in response to changes in load. Previously, we showed that after only 1 hour of linear pulsatile stretch (110% of resting cell length; 3 Hz), expression of connexin43 (Cx43) by cultured neonatal rat ventricular myocytes is increased by approximately 2-fold and impulse propagation is significantly more rapid. In the present study, we tested the hypothesis that vascular endothelial growth factor (VEGF), acting downstream of transforming growth factor-beta (TGF-beta), mediates stretch-induced upregulation of Cx43 expression by cardiac myocytes. Incubation of nonstretched cells with exogenous VEGF (100 ng/mL) or TGF-beta (10 ng/mL) for 1 hour increased Cx43 expression by approximately 1.8-fold, comparable to that observed in cells subjected to pulsatile stretch for 1 hour. Stretch-induced upregulation of Cx43 expression was blocked by either anti-VEGF antibody or anti-TGF-beta antibody. Stretch-induced enhancement of conduction was also blocked by anti-VEGF antibody. ELISA assay showed that VEGF was secreted into the culture medium during stretch. Furthermore, stretch-conditioned medium stimulated Cx43 expression in nonstretched cells. This effect was also blocked by anti-VEGF antibody. Upregulation of Cx43 expression stimulated by exogenous TGF-beta was blocked by anti-VEGF antibody, but VEGF-stimulation of Cx43 expression was not blocked by anti-TGF-beta antibody. Thus, stretch-induced upregulation of Cx43 expression is mediated, at least in part, by VEGF, which acts downstream of TGF-beta. Because the cultures contained only approximately 5% nonmyocytic cells, these results indicate that myocyte-derived VEGF, secreted in response to stretch, acts in an autocrine fashion to enhance intercellular coupling.