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Background The corrected QT interval (QTc) is a measure of ventricular repolarization time, and a prolonged QTc increases risk for malignant ventricular arrhythmias. Pulmonary vein isolation (PVI) may increase QTc but its effects have not been well studied. Objective Determine the incidence, risk factors, and outcomes of patients presenting for PVI in sinus and atrial fibrillation with postoperative QTc prolongation in a large cohort. Methods We performed a single-center retrospective study of consecutive atrial fibrillation ablations. QTc durations using Bazett correction were obtained from electrocardiograms at different postoperative intervals and compared to preoperative QTc. We studied clinical outcomes including clinically significant ventricular arrhythmia and death. A multivariable model was used to identify factors associated with clinically significant QTc prolongation, defined as ΔQTc ≥60 ms or new QTc duration ≥500 ms. Results A total of 352 PVIs were included in this study. We observed a statistically significant increase in mean QTc compared to baseline (446.3 ± 37.8 ms) on postoperative day (POD)0 (471.7 ± 38.2 ms, P < .001) and at POD1 (456.5 ± 35.0 ms, P < .001). There was no significant difference at 1 month (452.4 ± 33.5 ms, P = .39) and 3 months (447.3 ± 40.0 ms, P = .78). Sixty-six patients (19.2%) developed ΔQTc ≥60 ms or QTc ≥500 ms on POD0, with 4.1% persisting past 90 days. Female sex (odds ratio [OR] = 1.82, 95% confidence interval [CI] =1.01–3.29, P = .047) and history of coronary artery disease (OR = 2.16, 95% CI = 1.03–4.55, P = .042) were independently predictive of QTc prolongation ≥500 ms or ΔQTc ≥60 ms. There were no episodes of clinically significant ventricular arrhythmia or death attributable to arrhythmia. Conclusion QTc duration increased significantly immediately post-PVI and returned to baseline by 1 month. PVI did not provoke significant ventricular arrhythmias in our cohort., Graphical abstract

Introduction: Telerobotic operation in which a remote surgeon performs an operation over distance has long held the promise of providing a more equitable distribution of healthcare in rural and underserved regions of the world. One of the technological limitations that has hampered the adoption of telerobotic surgery is the need for a broadband connection to transmit high-resolution video of the operative field. Hypothesis: We hypothesized that we could develop a low-bandwidth system for telerobotic cardiac catheter ablation that deploys a virtual reality (VR)-based surgical guidance system to allow remote operation without the need for high-resolution video transmission. Methods: We assembled a portable pre-clinical telerobotic catheter ablation system from commercial-grade components by 3 rd party vendors. Raw sensor data from the catheter ablation system requiring a bitrate of less than 100kb/sec was streamed in real-time over distance using a standard internet connection. We used a proprietary service (DOPL Technologies, Seattle, WA) and an Oculus Quest (Oculus, Inc. Menlo Park, CA) to generate a shared, virtual operative field and operating room environment. No video data was transmitted. The Institutional Animal Care and Use Committee of the University of Washington (Seattle, WA) approved the study performed on a 14-week (27 kg) Yorkshire pig. The operator was located 6 miles from the OR at the time of the operation. Results: A successful proof of concept telerobotic cardiac catheter ablation in an animal model was performed without video transmission. The remote surgeon applied radiofrequency energy lesions in the animal’s cavotricuspid isthmus region. The visual depiction of the operative environment was successfully constructed in virtual reality from sensor data generated from the animal subject and surgical instruments. The remote operator conducted the ablation while interacting in a shared virtual OR environment with members of the surgical team present in the physical operating room and three remote observers. Conclusions: Telerobotic cardiac catheter ablation is feasible without video transmission. This approach could reduce network bandwidth requirements for telerobotic operations in rural areas.

Orthotropic heart transplantation remains the most effective therapy for patients with end-stage heart failure, with a median survival of ≈13 years. Yet, a number of complications are observed after orthotropic heart transplantation, including atrial and ventricular arrhythmias. Several factors contribute to arrhythmias, such as autonomic denervation, effect of the surgical technique, acute and chronic rejection, and transplant vasculopathy among others. To minimize risk of future arrhythmias, the bicaval technique and minimizing ischemic time are current surgical standards. Sinus node dysfunction is the most common indication for early (within 30 days) pacemaker implantation, whereas atrioventricular block incidence increases as time from transplant increases. Atrial fibrillation can occur in the first few weeks following transplantation but is uncommon in the long term unless secondary to a precipitant such as acute rejection. The most common atrial arrhythmias are atrial flutters, which are mainly typical, but atypical circuits can be observed such as those that involve the remnant donor atrium in regions immediately adjacent to the atrioatrial anastomosis suture line. Choosing the appropriate pharmacological therapy requires careful consideration due to the potential interaction with immunosuppressive agents. Despite historical concerns, adenosine is effective and safe at reduced doses if administered under cardiac monitoring. Catheter ablation has emerged as an effective treatment strategy for symptomatic supraventricular tachycardias, including ablation of atypical flutter circuits. Cardiac allograft vasculopathy is an important risk factor for sudden cardiac death, yet the role of prophylactic implantable cardioverter-defibrillator implant for sudden death prevention is unclear. Current indications for implantable cardioverter-defibrillator implantation are as in the nontransplant population. A number of questions for future research are posed.

Introduction We sought to determine the effectiveness and safety of hydroxychloroquine–azithromycin (HCQ-AZM) therapy in hospitalized patients with COVID-19. Methods This was a retrospective cohort study of 613 patients hospitalized (integrated health system involving three hospitals) for RT-PCR-confirmed COVID-19 infection between March 1, 2020 and April 25, 2020. Intervention was treatment with HCQ-AZM in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Outcomes of interest were in-hospital all-cause mortality, cardiovascular mortality, pulseless electrical activity (PEA) arrest, non-lethal arrhythmias, and length of hospital stay. Secondary measures included in-hospital corrected QT (QTc) interval parameters and serum biomarkers levels. Results Propensity-matched groups were composed of 173 patients given HCQ-AZM and 173 matched patients who did not receive treatment. There was no significant difference in in-hospital mortality (odds ratio [OR] 1.52; 95% confidence interval [CI] 0.80–2.89; p = 0.2), PEA arrest (OR 1.68, CI 0.68–4.15; p = 0.27), or incidence of non-lethal arrhythmias (10.4% vs. 6.8%; p = 0.28). Length of hospital stay (10.5 ± 7.4 vs. 5.8 ± 6.1; p

Background Observational studies have suggested increased arrhythmic and cardiovascular risk with the combination use of hydroxychloroquine (HCQ) and azithromycin in patients with coronavirus disease 2019 (COVID-19). Objective The arrhythmic safety profile of HCQ monotherapy, which remains under investigation as a therapeutic and prophylactic agent in COVID-19, is less established and we sought to evaluate this. Methods In 245 consecutive patients with COVID-19 admitted to the University of Washington hospital system between March 9, 2020, and May 10, 2020, we identified 111 treated with HCQ monotherapy. Patients treated with HCQ underwent a systematic arrhythmia and QT interval surveillance protocol including serial electrocardiograms (ECG) (baseline, following second HCQ dose). The primary endpoint was in-hospital sustained ventricular arrhythmia or arrhythmic cardiac arrest. Secondary endpoints included clinically significant QTc prolongation. Results A total of 111 patients with COVID-19 underwent treatment with HCQ monotherapy (mean age 62 ± 16 years, 44 women [39%], serum creatinine 0.9 [interquartile range 0.4] mg/dL). There were no instances of sustained ventricular arrythmia or arrhythmic cardiac arrest. In 75 patients with serial ECGs, clinically significant corrected QT (QTc) prolongation was observed in a minority (n = 5 [7%]). In patients with serial ECGs, there was no significant change in the QTc interval in prespecified subgroups of interest, including those with prevalent cardiovascular disease or baseline use of renin-angiotensin-aldosterone axis inhibitors. Conclusions In the context of a systematic monitoring protocol, HCQ monotherapy in hospitalized COVID-19 patients was not associated with malignant ventricular arrhythmia. A minority of patients demonstrated clinically significant QTc prolongation during HCQ therapy.

The efficacy of novel oral anticoagulants (NOACs) in severely obese patients is uncertain as volume of distribution is related to weight, and few such patients were enrolled in the pivotal trials. As the month after direct-current cardioversion (DCCV) for atrial fibrillation and atrial flutter is a high-risk period for stroke, we sought to evaluate the safety of performing DCCV in obese patients on NOAC. All patients who underwent DCCV after ≥3 weeks of NOAC or therapeutic warfarin treatment without a previous transesophageal echocardiogram over a 3-year period at a single center were included. Obesity groups were defined as normal (body mass index [BMI] < 25), overweight (BMI 25 to

Hemodialysis (HD) patients have a high risk of sudden death but limited vascular access and high complication rates from transvenous implantable cardioverter-defibrillators (ICDs). Subcutaneous ICDs (S-ICD) may be an alternative, but dynamic ECG changes may result in inappropriate shocks. This study aims to define the screen failure rate for S-ICD in patients pre- and post-HD. ECG waveforms were obtained using electrodes mimicking the S-ICD sensing vectors in an unselected test group of chronic HD patients and a control group of ICD-eligible non-dialysis patients. Participants passed screening if their QRS and T-waves fit within the screening template in supine and standing positions in any lead. Test group participants were screened before and after HD and control group patients were screened at two separate time points. HD patients were stratified into the four following groups: (A) passed screening before and after HD, (B) failed screening before but passed after HD, (C) passed screening before but failed after HD, and (D) failed screening before and after HD. Patients in group A passed the screening for ICD implantation, and patients in groups B, C, and D failed the screening for ICD implantation. Control patients were similarly classified by pass/fail status at the two assessment points. Of the 76 patients enrolled, 51 were HD patients and 25 were controls. Of the 51 HD patients, 43 (84%) were in group A, four participants (8%) were in group B, one (2%) was in group C, and three participants (6%) were in group D. There were no differences in any of the clinical or demographic variables between the pass and fail test HD groups. None of the 25 controls failed the screening at either time point (p = 0.047 vs HD patients). Overall, HD patients were more likely to fail S-ICD screening compared to non-HD patients (16 v 0%, p = 0.047) and are more likely to do so prior to HD. Patients on HD should be screened at multiple time points around the dialytic interval to reduce the risk of inappropriate shocks.

Subcutaneous implantable cardioverter defibrillators (S‐ICD) have become a reasonable alternative to single‐chamber transvenous ICD systems for patients who pass the screening protocol.1, 2 There is limited experience however in managing patients who require a sternotomy who have previously had a S‐ICD placed. Concerns over lead damage, lead positioning poststernotomy, and possible contact between the lead and the sternotomy wires are the main concerns that may result in device malfunction.

The Centers for Diseases Control and Prevention estimates that 5.7 million adults in the United States suffer from heart failure and 1 in 9 deaths in 2009 cited heart failure as a contributing cause. Almost 50% of patients who are diagnosed with heart failure die within 5 years of diagnosis. Cardiovascular disease is a public health burden. The prognosis of patients with heart failure has improved significantly. However, the risk for death remains high. Managing sudden death risk and intervening appropriately with primary or secondary prevention strategies are of paramount importance.

Background: The potential benefits of implantable cardioverter-defibrillator (ICD) therapy in patients with sudden cardiac death (SCD) treated with therapeutic hypothermia (TH) have not been well studied. Methods: Incidence of recurrent non-sustained ventricular arrhythmia, ICD therapy, and death were ascertained in 64 consecutive survivors of SCD due to ventricular fibrillation or tachycardia, who were treated with TH. Follow-up was 31.5 +/- 3.3 months in 41 ICD recipients and 36.3 +/- 3.9 months in 23 patients who did not receive an ICD due to the presence of a reversible cause of cardiac arrest, an acute myocardial infarction in 87%. Results: Combined incidence of ventricular arrhythmia, ICD therapy, or death in patients who underwent ICD placement (21.9%) were similar to overall mortality in the patients who did not receive an ICD (21.7%, p = 0.752). ICD placement was associated with a significant mortality benefit; 95.1% survival in ICD recipients vs. 78.3% in the no-ICD group (p = 0.038). Electrocardiographic findings of ST segment elevation on admission were associated with increased event rate in ICD recipients (p = 0.039) and increased mortality in SCD patients who did not receive an ICD (p < 0.001). Other studied variables had no significant effect on the investigated outcomes. Conclusions: SCD survivors treated with TH are at increased risk for recurrent arrhythmic events and derive significant mortality benefit from ICD implantation. Increased mortality in revascularized SCD patients with acute coronary syndrome, thought to have a reversible cause of cardiac arrest, calls for prospective trials investigating utility of ICD in this vulnerable patient population.

Leadless pacemakers were developed to reduce complications associated with transvenous pacemaker implant and long-term follow-up. Since initial market release, however, there have been registry and single-center reports documenting improvements in implant technique, reduced complication rates, and new patient populations studied. Most studies have demonstrated a further reduction in complication rates and safe implant in those on continuous anticoagulation. Perforation rates are decreasing but still occur and risk factors include BMI

BACKGROUND The perioperative management of anticoagulation with the use of subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation is still evolving. OBJECTIVE The purpose of this study was to assess whether it is safe to perform S-ICD implantation with uninterrupted warfarin. METHODS This is a multi-center retrospective review of patients undergoing S-ICD implantation between October 1, 2012 and June 30, 2017. Forty-eight patients underwent successful S-ICD implantation during the study period. The most common indication for implantation was primary prevention of sudden cardiac death. In 23 (47.9%) patients, warfarin was continued without any interruption. In 25 (52.1%) patients, warfarin was interrupted prior to implantation. The incidence of clinically significant lateral pocket hematoma was compared in the two groups. RESULTS The mean international normalized ratio was 2.0 ± 0.4 in the uninterrupted group and 1.4 ± 0.4 for the interrupted group. A total of seven patients developed a hematoma at the lateral pocket. No patient developed a hematoma at the parasternal pockets. Six patients in the uninterrupted group (26.1%) and one patient in the interrupted group (0.04%) developed a significant lateral pocket hematoma (P = .04). The concomitant use of dual antiplatelet therapy did not increase the risk of hematoma. There was no significant difference between HASBLED and CHA2 DS2 VASc scores between the groups. None of the patients with a hematoma developed infection or required hematoma evacuation. CONCLUSIONS The uninterrupted use of warfarin in the perioperative period of S-ICD implantation is associated with an increased risk of lateral pocket hematoma.

Purpose: We hypothesized that advanced circulatory compromise, as manifested by acidosis and hyperkalemia should be associated with worsened clinical outcomes in cardiac arrest patients treated with therapeutic hypothermia. Methods: Results of initial admission laboratory studies, medical history, and echocardiogram in 203 consecutive cardiac arrest patients (59 females, 59+/- 15 years old) undergoing therapeutic hypothermia were reviewed. Mortality was ascertained through hospital records. ANOVA, chi-square, Kaplan-Meier, and logistic regression analyses were used. The study was approved by the institutional IRB. Results: Increased mortality was noted with older age, decreased admission pH, elevated admission lactate, lower admission hemoglobin, and pulseless electrical activity or asystole as presenting rhythms (Table). Admission hypokalemia and ventricular fibrillation/tachycardia were associated with improved hospital mortality (Table). Potassium was significantly lower in patients admitted with ventricular fibrillation/tachycardia (3.897+/-0.92) as compared to patients with asystole (4.674+/-1.377) or pulseless electrical activity (4.491+/-1.055 mEq/dL, p Conclusions: Hyperkalemia, pulseless electrical activity, and asystole are predictive of increased hospital mortality in survivors of cardiac arrest. An association between low or low-normal potassium, observed VT-VF, and better outcomes is unexpected and may be used for prognostic purposes. More prospective investigations of mortality predictors in these critically ill patients are needed.

Atherosclerotic cardiovascular disease (CVD) is highly prevalent and, despite therapeutic advances, remains a leading cause of morbidity and mortality. Many patients with CVD seek additional alternative therapies when symptoms are not controlled with evidence-based therapies. Although its therapeutic efficacy is unproven, chelation therapy with ethylenediamine tetra acetic acid (EDTA) is increasingly being used in patients with CVD. Early studies of chelation in atherosclerotic CVD provided the basis for the randomized Trial to Assess Chelation Therapy (TACT), in which chelation with disodium EDTA was compared with placebo in patients who had experienced a myocardial infarction. Here, we discuss the results, limitations, and implications of TACT in the context of other studies in the field. We believe that the findings from TACT are not robust and do not marshal evidence in support of the potential clinical use of chelation therapy for CVD, with the potential exception of certain high-risk cohorts such as patients with diabetes mellitus. Therefore, chelation is unlikely to become a widely-accepted approach until additional data are available.

Novel oral anticoagulants (NOACs) are used in patients undergoing direct-current cardioversion (DCCV) for atrial fibrillation and atrial flutter (AF/AFL). There are concerns about their efficacy and safety in severely obese patients as volume of distribution is related to weight and few such

Central venous stenosis is a common complication of the transvenous leads associated with an implantable cardioverter defibrillator (ICD). Although epicardial leads have been reported to bypass this complication, their placement is much more invasive than the subcutaneous ICDs (SICDs) and requires the services of a cardiothoracic surgeon. Recent data have demonstrated successful defibrillation using an SICD. In this report, we present 4 long-term hemodialysis patients treated successfully with an SICD. 3 patients received the device for primary prevention of sudden cardiac death (cardiomyopathy with low ejection fraction). The patient in the fourth case had a prolonged QT interval and received the device for secondary prevention. 3 patients had an arteriovenous fistula, whereas 1 patient was dialyzing with a tunneled dialysis catheter. Insertion of an SICD is a minimally invasive procedure. By virtue of leaving the venous system untouched, this approach might offer the advantage of reduced risk of central venous stenosis and infection over an endocardial ICD with transvenous leads. SICD is not experimental; it has been approved by the US Food and Drug Administration and is currently being used in the United States and Europe.

Background: We investigated changes in myocardial repolarization and associated outcomes in patients undergoing therapeutic hypothermia after cardiac arrest. Methods: Demographic, clinical, and ECG data on 19 consecutive cardiac arrest survivors (6 females, 59+/-15 years old, 3 with diabetes, 3 with cancer, 3 with CKD, 5 with pulmonary disease and 5 with cardiovascular disease) undergoing therapeutic hypothermia were collected. Absolute QT dispersion was calculated. ANOVA, chi-square, Kaplan-Meier and logistic regression analyses were used. The study was approved by the IRB. Results: Hypothermia resulted in significant prolongation of both minimum (baseline 277+/-74 vs. cooled 408+/-129 vs. re=warmed 313+/-82 msec, p Conclusion: Therapeutic hypothermia is associated with significantly prolonged QT intervals. However, these QT abnormalities do not translate into increased mortality and/or AICD therapy during short or long-term follow-up.

We have previously demonstrated the antiproliferative effect of two flavonoids-2,2'-dihydroxychalcone (DHC), a novel synthetic flavonoid, and fisetin, a naturally occurring flavonol-in prostate cancer cells. In this study, we further examine the mechanisms of these compounds on survival and proliferation pathways. DHC and fisetin (1-50 microM) caused a dose-dependent reduction in viability, a concomitant increase in apoptosis in PC3 cells at 72 h, and a decrease in clonogenic survival at 24 h treatment. DHC was considerably more potent than fisetin in these cytotoxicity assays. The mechanism of accelerated cellular senescence was not activated by either compound in PC3 or lymph node carcinoma of the prostate (LNCaP) cells. Gene expression alterations in PC3 and LNCaP cells treated with 15 muM DHC and 25 microM fisetin for 6 to 24 h were determined by oligonucleotide array. Amongst the most highly represented functional categories of genes altered by both compounds was the cell cycle category. In total, 100 cell cycle genes were altered by DHC and fisetin including 27 genes with key functions in G2/M phase that were downregulated by both compounds. Other functional categories altered included chromosome organization, apoptosis, and stress response. These results demonstrate the multiple mechanisms of antitumor activity of DHC and fisetin in prostate cancer cells in vitro.