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Muscarinic acetylcholine receptors (mAChRs) (nomenclature as agreed by the NC-IUPHAR Subcommittee on Muscarinic Acetylcholine Receptors [53]) are activated by the endogenous agonist acetylcholine. All five (M1-M5) mAChRs are ubiquitously expressed in the human body and are therefore attractive targets for many disorders. Functionally, M1, M3, and M5 mAChRs preferentially couple to Gq/11 proteins, whilst M2 and M4 mAChRs predominantly couple to Gi/o proteins. Both agonists and antagonists of mAChRs are clinically approved drugs, including pilocarpine for the treatment of elevated intra-ocular pressure and glaucoma, and atropine for the treatment of bradycardia and poisoning by muscarinic agents such as organophosphates. Of note, it has been observed that mAChRs dimerise reversibly [134] and that dimerisation/oligomerisation can be affected by ligands [183, 196].

Introduction: Successful synchronized direct current cardioversion (DCCV) requires adequate current delivery to the heart. However, adequate current for successful DCCV is not yet established. Trans-myocardial current depends on two factors: input energy and transthoracic impedance (TTI). While factors affecting TTI have been studied in animal models, factors affecting TTI in humans have not been well established. Here we explored potential factors that affect TTI in humans. Methods: Retrospective review of consecutive patients undergoing DCCV at a large quaternary medical center between October 2019 and December 2020 was conducted. Pertinent clinical information, including demographics, echocardiography findings, laboratory findings and body characteristics were collected. Cardioversion details including joules delivered and TTI were recorded by the defibrillator for each patient’s first shock. Predictors of thoracic impedance were assessed using multivariable regression analysis after adjustment for confounders. Results: A total of 180 patients were analyzed, 31% of which were female. Mean impedance was 73.15 ± 21.50 (range 39-208). In multivariate analysis, higher TTI was significantly associated with higher BMI (pFigure ) and female gender (p=0.006) after adjustment for all confounders. Other factors including age, history of cardiac surgery, left ventricular ejection fraction, left atrial size, brain natriuretic peptide, and antero-posterior chest diameter were not associated with TTI. Conclusion: Our results align with prior studies that body habitus and gender affect TTI and suggest that adjustments in input energy based on these factors may be required for appropriate trans-myocardial current delivery in synchronized cardioversion.

There is growing evidence that COVID-19 can cause cardiovascular complications. However, there are limited data on the characteristics and importance of atrial arrhythmia (AA) in patients hospitalized with COVID-19. Data from 1,029 patients diagnosed with of COVID-19 and admitted to Columbia University Medical Center between March 1, 2020 and April 15, 2020 were analyzed. The diagnosis of AA was confirmed by 12 lead electrocardiographic recordings, 24-hour telemetry recordings and implantable device interrogations. Patients' history, biomarkers and hospital course were reviewed. Outcomes that were assessed were intubation, discharge and mortality. Of 1,029 patients reviewed, 82 (8%) were diagnosed with AA in whom 46 (56%) were new-onset AA 16 (20%) recurrent paroxysmal and 20 (24%) were chronic persistent AA. Sixty-five percent of the patients diagnosed with AA (n=53) died. Patients diagnosed with AA had significantly higher mortality compared with those without AA (65% vs 21%; p < 0.001). Predictors of mortality were older age (Odds Ratio (OR)=1.12, [95% Confidence Interval (CI), 1.04 to 1.22]); male gender (OR=6.4 [95% CI, 1.3 to 32]); azithromycin use (OR=13.4 [95% CI, 2.14 to 84]); and higher D-dimer levels (OR=2.8 [95% CI, 1.1 to 7.3]). In conclusion, patients diagnosed with AA had 3.1 times significant increase in mortality rate versus patients without diagnosis of AA in COVID-19 patients. Older age, male gender, azithromycin use and higher baseline D-dimer levels were predictors of mortality.

Background Cardiovascular involvement in coronavirus disease 2019 (COVID‐19) is common and leads to worsened mortality. Diagnostic cardiovascular studies may be helpful for resource appropriation and identifying patients at increased risk for death. Methods and Results We analyzed 887 patients (aged 64±17 years) admitted with COVID‐19 from March 1 to April 3, 2020 in New York City with 12 lead electrocardiography within 2 days of diagnosis. Demographics, comorbidities, and laboratory testing, including high sensitivity cardiac troponin T (hs‐cTnT), were abstracted. At 30 days follow‐up, 556 patients (63%) were living without requiring mechanical ventilation, 123 (14%) were living and required mechanical ventilation, and 203 (23%) had expired. Electrocardiography findings included atrial fibrillation or atrial flutter (AF/AFL) in 46 (5%) and ST‐T wave changes in 306 (38%). 27 (59%) patients with AF/AFL expired as compared to 181 (21%) of 841 with other non‐life‐threatening rhythms ( P Conclusions Myocardial injury with hs‐cTnT ≥20 ng/L, in addition to cardiac conduction perturbations, especially AF/AFL, upon hospital admission for COVID‐19 infection is associated with markedly increased risk for mortality than either diagnostic abnormality alone.

Introduction: Both typical cavo-tricuspid isthmus (CTI) dependent (or its equivalent) and atypical atrial flutter (AFL) are common in adults with congenital heart disease (CHD) either due to its inherent cardiac anatomy or as a result of prior surgical procedures. Radiofrequency catheter ablation is routinely used as a therapeutic option. Hypothesis: Patients with CHD will have an improvement in systemic ventricular ejection fraction and a decreased incidence of atrial arrhythmias after ablation. Methods: A retrospective study was conducted on 99 patients with CHD who underwent ablation for clinical AFL at a single institution between 2010 and 2019. Of these patients, 62 had CTI-AFL. The 2 patients with unspecified CHD were excluded. CHD was divided into 3 categories according to the American College of Cardiology Task Force 1 of the 32nd Bethesda Conference - simple, moderate severity, and great complexity lesions. Outcomes of ablation at 1 year follow up were assessed. Results: Typical counterclockwise CTI-AFL was seen in 50 patients. The mean age was 49.1±13.6 years old with 29 (48.3%) females. Of the 60 patients, 35% (n=21) had simple lesions, 51.7% (n=31) had moderate lesions, and 13.3% (n=8) had great complexity lesions. The mean left or systemic ventricular ejection fraction (EF) significantly improved on follow-up echo among patients with simple CHD (49.1±13.1 to 56.5±4.7%, p=0.018) and moderate CHD (49.5±14.9 to 54±8.5%, p=0.02), but did not change among patients with great complexity CHD (52.5±6 to 52.5±9.25%, p=0.9). There was a significantly increased incidence of atrial fibrillation (9.5% vs. 16.1% vs. 50%, p=0.04) post ablation among simple, moderate, and great complexity lesions, respectively, but no significant difference in the recurrence rate of atrial flutter (p=0.3). Conclusions: Patients who underwent CTI-AFL ablation showed an improvement in EF in patients with simple and moderate CHD. There was also a significantly increased incidence in the development of atrial fibrillation post ablation in CHD with great complexity compared to simple or moderate CHD.

Introduction: Atrial arrhythmias (AA) are common after lung transplant (LT) and may impact overall mortality. The majority of arrhythmias tend to be organized flutter, amenable to ablation; however the data is limited. Hypothesis: The purpose of this study was to investigate the outcomes of radiofrequency catheter ablation of AA in LT recipients. Methods: All LT recipients undergoing electrophysiology study at our institution between 2011-2018 were retrospectively reviewed. A total of 20 atrial ablations were identified in 16 patients. Mean follow-up was 4 ± 2.9 years. Results: Overall, mean age was 55 ± 13 years, 63% were male, 63% were status post bilateral (vs. single) LT, and mean LVEF was 57%. Transplant indications included interstitial lung disease (44%), COPD (19%), and cystic fibrosis (19%). Antiarrhythmics and beta blockers were used in 44% and 75%, respectively. Mean time from transplant to first ablation was 2.7 years. Of 20 ablations, macro-reentrant flutter (75%) and focal atrial tachycardia (15%) were common, particularly in double LT recipients (Figure). The most common ablation sites were pulmonary vein anastomosis/left atrial ridge (60%), mitral annulus (35%) and left atrial roof (30%). Restoration of sinus rhythm occurred in 19 of 20 procedures and only one complication occurred (e.g. small pericardial effusion without tamponade). Arrhythmia recurred in 10 (63%) patients, however, most were managed conservatively. Repeat ablation was needed in 4 patients, of which AAs originated from different locations. Beta blocker use was associated with a lower risk of SVT recurrence (p=0.04). Reduced LVEF and longer time to procedure post-transplant were associated with repeat ablation (p Conclusions: The majority of AAs in LT recipients are atrial flutter originating near the pulmonary vein anastomosis sites. Despite a high immediate procedural success rate, recurrence is high and 25% of patients require multiple ablation attempts.

Introduction: Cavo-tricuspid isthmus (CTI) dependent atrial flutter (AFL) is one of the most common atrial arrhythmias involving the right atrium (RA) for which radiofrequency catheter ablation has been widely used as a therapy of choice. However, there is limited data on the effect of this intervention on cardiac size and function. Hypothesis: CTI dependent ablation for patients with AFL will improve tricuspid valve function, biatrial enlargement, and ventricular function. Methods: A retrospective study was conducted on 468 patients who underwent CTI dependent ablation for clinical typical AFL at a single institution between 2010 and 2019. After patients with congenital or rheumatic heart disease, heart transplant recipients, or those without baseline echocardiogram were excluded, 211 patients remained in the analysis. Echocardiographic data were analyzed at baseline prior to ablation, and at early follow-up within 1-year post-ablation. Follow-up echocardiographic data was available for 130 patients. Results: Of the 211 patients with CTI-AFL, 200 had typical counterclockwise flutter. The mean age was 64.2±12.1 years old with 12% (n=26) female. The average left ventricular (LV) ejection fraction (EF) significantly improved on follow-up echo (45.55±14.26 to 49±14.4%, p=0.0075), of which 63 (48%) patients had an improvement in EF of 5% or more and 19 (25%) patients had an increased EF of 20% or more. The prevalence of moderate to severe tricuspid regurgitation (TR) was 24% (n=50) at baseline and 18% (n=22) at follow-up with no significant difference (p=0.27). However, 30% (n=39) of the patients had one grade or more improvement in their TR within the 1-year follow-up. Echocardiography also showed improvement of RA size in 48.6%, and left atrial (LA) size in 48.2% of the patients. Conclusions: Patients who underwent CTI dependent AFL ablation showed an improvement in cardiac size and function at follow-up evaluation. Although longer-term results are unknown, these findings suggest that restoration of sinus rhythm from atrial flutter is associated with improvement in TR severity, RA size, LA size, and LVEF.

Objective To study whether combining vital signs and electrocardiogram (ECG) analysis can improve early prognostication. Methods This study analyzed 1258 adults with coronavirus disease 2019 who were seen at three hospitals in New York in March and April 2020. Electrocardiograms at presentation to the emergency department were systematically read by electrophysiologists. The primary outcome was a composite of mechanical ventilation or death 48 hours from diagnosis. The prognostic value of ECG abnormalities was assessed in a model adjusted for demographics, comorbidities, and vital signs. Results At 48 hours, 73 of 1258 patients (5.8%) had died and 174 of 1258 (13.8%) were alive but receiving mechanical ventilation with 277 of 1258 (22.0%) patients dying by 30 days. Early development of respiratory failure was common, with 53% of all intubations occurring within 48 hours of presentation. In a multivariable logistic regression, atrial fibrillation/flutter (odds ratio [OR], 2.5; 95% CI, 1.1 to 6.2), right ventricular strain (OR, 2.7; 95% CI, 1.3 to 6.1), and ST segment abnormalities (OR, 2.4; 95% CI, 1.5 to 3.8) were associated with death or mechanical ventilation at 48 hours. In 108 patients without these ECG abnormalities and with normal respiratory vitals (rate 95%), only 5 (4.6%) died or required mechanical ventilation by 48 hours versus 68 of 216 patients (31.5%) having both ECG and respiratory vital sign abnormalities. Conclusion The combination of abnormal respiratory vital signs and ECG findings of atrial fibrillation/flutter, right ventricular strain, or ST segment abnormalities accurately prognosticates early deterioration in patients with coronavirus disease 2019 and may assist with patient triage.

The coronavirus disease 2019 crisis is a global pandemic of a novel infectious disease with far-ranging public health implications. With regard to cardiac electrophysiology (EP) services, we discuss the “real-world” challenges and solutions that have been essential for efficient and successful (1) ramping down of standard clinical practice patterns and (2) pivoting of workflow processes to meet the demands of this pandemic. The aims of these recommendations are to outline: (1) essential practical steps to approaching procedures, as well as outpatient and inpatient care of EP patients, with relevant examples, (2) successful strategies to minimize exposure risk to patients and clinical staff while also balancing resource utilization, (3) challenges related to redeployment and restructuring of clinical and support staff, and (4) considerations regarding continued collaboration with clinical and administrative colleagues to implement these changes. While process changes will vary across practices and hospital systems, we believe that these experiences from 4 different EP sections in a large New York City hospital network currently based in the global epicenter of the coronavirus disease 2019 pandemic will prove useful for other EP practices adapting their own practices in preparation for local surges.

A global coronavirus (COVID‐19) pandemic occurred at the start of 2020 and is already responsible for more than 74 000 deaths worldwide, just over 100 years after the influenza pandemic of 1918. At the center of the crisis is the highly infectious and deadly SARS‐CoV‐2, which has altered everything from individual daily lives to the global economy and our collective consciousness. Aside from the pulmonary manifestations of disease, there are likely to be several electrophysiologic (EP) sequelae of COVID‐19 infection and its treatment, due to consequences of myocarditis and the use of QT‐prolonging drugs. Most crucially, the surge in COVID‐19 positive patients that have already overwhelmed the New York City hospital system requires conservation of hospital resources including personal protective equipment (PPE), reassignment of personnel, and reorganization of institutions, including the EP laboratory. In this proposal, we detail the specific protocol changes that our EP department has adopted during the COVID‐19 pandemic, including performance of only urgent/emergent procedures, after hours/7‐day per week laboratory operation, single attending‐only cases to preserve PPE, appropriate use of PPE, telemedicine and video chat follow‐up appointments, and daily conferences to collectively manage the clinical and ethical dilemmas to come. We discuss also discuss how we perform EP procedures on presumed COVID positive and COVID tested positive patients to highlight issues that others in the EP community may soon face in their own institution as the virus continues to spread nationally and internationally.

Infections after placement of cardiac implantable electronic devices (CIEDs) are associated with substantial morbidity and mortality. There is limited evidence on prophylactic strategies, other than the use of preoperative antibiotics, to prevent such infections.We conducted a randomized, controlled clinical trial to assess the safety and efficacy of an absorbable, antibiotic-eluting envelope in reducing the incidence of infection associated with CIED implantations. Patients who were undergoing a CIED pocket revision, generator replacement, or system upgrade or an initial implantation of a cardiac resynchronization therapy defibrillator were randomly assigned, in a 1:1 ratio, to receive the envelope or not. Standard-of-care strategies to prevent infection were used in all patients. The primary end point was infection resulting in system extraction or revision, long-term antibiotic therapy with infection recurrence, or death, within 12 months after the CIED implantation procedure. The secondary end point for safety was procedure-related or system-related complications within 12 months.A total of 6983 patients underwent randomization: 3495 to the envelope group and 3488 to the control group. The primary end point occurred in 25 patients in the envelope group and 42 patients in the control group (12-month Kaplan-Meier estimated event rate, 0.7% and 1.2%, respectively; hazard ratio, 0.60; 95% confidence interval [CI], 0.36 to 0.98; P = 0.04). The safety end point occurred in 201 patients in the envelope group and 236 patients in the control group (12-month Kaplan-Meier estimated event rate, 6.0% and 6.9%, respectively; hazard ratio, 0.87; 95% CI, 0.72 to 1.06; P0.001 for noninferiority). The mean (±SD) duration of follow-up was 20.7±8.5 months. Major CIED-related infections through the entire follow-up period occurred in 32 patients in the envelope group and 51 patients in the control group (hazard ratio, 0.63; 95% CI, 0.40 to 0.98).Adjunctive use of an antibacterial envelope resulted in a significantly lower incidence of major CIED infections than standard-of-care infection-prevention strategies alone, without a higher incidence of complications. (Funded by Medtronic; WRAP-IT ClinicalTrials.gov number, NCT02277990.).

Left ventricular assist device (LVAD) therapy improves survival and quality of life by mechanically unloading the left ventricle and maintaining hemodynamics in patients with end-stage heart failure. LVADs can also be lifesaving by maintaining hemodynamics during ventricular arrhythmia. Continuous-flow LVADs have become the preferred LVAD technology. As presented here, a continuous-flow LVAD successfully provided hemodynamic support to a patient in sustained ventricular fibrillation for over 12 hours when the internal defibrillator was unable to terminate the arrhythmia. This case demonstrates that continuous-flow LVADs can be lifesaving in the setting of otherwise certain hemodynamic collapse from sustained ventricular fibrillation.

Aims Chronotropic incompetence (CI) is a common finding in patients with advanced chronic heart failure (CHF) and is associated with a worse functional capacity. Whether rate responsive pacing with cardiac resynchronization therapy (CRT) would acutely improve exercise performance in patients with advanced CHF and severe CI (

Aims Isthmus-dependent right atrial flutter (RAFL) is a common sequela of pulmonary vein isolation (PVI). It is unclear as to whether RAFL is a result of PVI or a concealed phenomenon unmasked by the elimination of atrial fibrillation (AF). We measured low right atrial conduction times (LRACTs) before and after PVI and examined their relationship to the inducibility of RAFL. Methods and results Twenty consecutive patients with paroxysmal AF but no history of RAFL were studied during the initial PVI procedure by radiofrequency ablation. Antiarrhythmic agents were discontinued for at least five half-lives. The clockwise and counterclockwise LRACTs were measured before and after PVI by pacing the proximal coronary sinus or low-lateral RA. Programmed atrial stimulation was performed post-PVI. Right atrial flutter, if inducible, was confirmed by entrainment mapping. Right atrial flutter was induced in six patients (Group A). No arrhythmias or only AF was induced in the remaining 14 patients (Group B). The average change in the clockwise LRACT was 19.8 ± 17.5 ms in Group A vs. 0.3 ± 10.7 ms in Group B ( P < 0.05). The average change in the counterclockwise LRACT was 25.7 ± 30.4 ms in Group A vs. 0.0 ± 6.7 ms in Group B ( P < 0.05). There were no significant differences between the groups in absolute LRACT or number of ablation lesions around the right pulmonary veins. Conclusion Right atrial flutter post-PVI is associated with prolongation of LRACTs. Ablation over the septal left atrium near the posterior right atrium during isolation of the right pulmonary veins may cause conduction delays that can lead to RAFL.

Objectives Ventricular resynchronization might be achieved in a minimally invasive fashion using a robotically assisted, direct left ventricular (LV) epicardial approach. Background Approximately 10% of patients undergoing biventricular pacemaker insertion have a failure of coronary sinus (CS) cannulation. Rescue therapy for these patients currently is limited to standard open surgical techniques. Methods Ten patients with congestive heart failure (New York Heart Association class 3.4 ± 0.5) and a widened QRS complex (184 ± 31 ms) underwent robotic LV lead placement after failed CS cannulation. Mean patient age was 71 ± 12 years, LV ejection fraction (EF) was 12 ± 6%, and LV end-diastolic diameter was 7.1 ± 1.3 cm. Three patients had previous cardiac surgery, and five patients had a prior device implanted. Results Nineteen epicardial leads were successfully placed on the posterobasal surface of the LV. Intraoperative lead threshold was 1.0 ± 0.5 V at 0.5 ms, R-wave was 18.6 ± 8.6 mV, and impedance was 1,143 ± 261 ohms at 0.5 V. Complications included an intraoperative LV injury and a postoperative pneumonia. Improvements in exercise tolerance (8 of 10 patients), EF (19 ± 13%, p = 0.04), and QRS duration (152 ± 21 ms, p = 0.006) have been noted at three to six months follow-up. Lead thresholds have remained unchanged (2.1 ± 1.4 V at 0.5 ms, p = NS), and a significant drop in impedance (310 ± 59 ohms, p Conclusions Robotic LV lead placement is an effective and novel technique which can be used for ventricular resynchronization therapy in patients with no other minimally invasive options for biventricular pacing.

The PAD Trial is a prospective, multicenter, randomized clinical study testing whether volunteer, non-medical responders can improve survival from out-of-hospital cardiac arrest (OOH-CA) by using automated external defibrillators (AEDs). These lay volunteers, who have no traditional responsibility to respond to a medical emergency as part of their primary job description, will form part of a comprehensive, integrated community approach to the treatment of OOH-CA. The study is being conducted at 24 field centers in the United States and Canada. Approximately 1000 community units (e.g. apartment or office buildings, gated communities, sports facilities, senior centers, shopping malls, etc.) were randomized to treatment by trained laypersons who will provide either cardiopulmonary resuscitation (CPR) alone or CPR plus use of an AED, while awaiting arrival of the community's emergency medical services responders. The primary endpoint is the number of OOH-CA victims who survive to hospital discharge. Secondary endpoints include neurological status, health-related quality of life (HRQL), cost, and cost-effectiveness. Data collection will last approximately 15 months and is expected to be completed in September 2003.

Unexplained Syncope in AVID.Introduction: A prospective registry and substudy were conducted in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Study to clarify the prognosis and recurrent event rate, risk factors, and impact of implantable cardioverter defibrillator (ICD) therapy in patients with unexplained syncope, structural heart disease, and inducible ventricular tachyarrhythmias. Methods and Results: Included in the AVID registry were patients from all participating sites who had “out of hospital syncope with structural heart disease and EP-inducible VT/VF with symptoms.” In addition, 13 collaborating sites provided more in-depth clinical and electrophysiologic data as part of a formal prospective substudy. Patients in the substudy were followed by local investigators for recurrent arrhythmic events and mortality. Registry patients were tracked for fatal outcomes by the National Death Index. A total of 429 patients with syncope were entered in the AVID registry, of whom 80 participated in the substudy. Of the substudy patients, 21 patients (26%) had inducible polymorphic ventricular tachycardia/ventricular fibrillation (VT/VF), 11 patients (14%) had sustained monomorphic VT < 200 beats/min, and 48 patients (60%) had sustained monomorphic VT ≥200 beats/min. The ICD was used as sole therapy in 75% of the syncope substudy patients (and with antiarrhythmic drug in an additional 9%) and in 59% of the syncope registry patients. Survival rates at 1 and 3 years were 93% and 74% for the substudy patients and 90% and 74% for the registry patients, respectively. Survival of the syncope substudy patients (predominantly treated by ICD) was similar to the VT patients treated by ICD and superior to the VT patients treated by an antiarrhythmic drug (P = 0.05) in the randomized main trial. Mortality events in the substudy were marginally predicted by ejection fraction (P = 0.06) but not by electrophysiologic study-induced arrhythmia. The significant predictor of increased mortality in the registry was age (P = 0.003) and of reduced mortality was treatment with ICD (P = 0.006). Conclusion: The results of these analyses support the role of the ICD as primary antiarrhythmic therapy in patients with unexplained syncope, structural heart disease, and inducible VT/VF at electrophysiologic study.

The comparison of patients with long-standing implantable cardioverter-defibrillators (ICDs) who have had or never have had appropriate therapy for ventricular arrhythmias may offer insight into potential risk factors that may improve patient selection.Records from patients in the Columbia Presbyterian device clinic whose original ICD was implanted before 31 December 2004 were analysed. The patients were divided into those who had never received appropriate therapy for ventricular arrhythmias (Group A, n = 188), and those who had received appropriate therapy (Group B, n = 173). The subset of patients with consistent follow-up greater than 5 years was then analysed (Group A, n = 140; Group B, n = 158). Demographic, clinical, echocardiographic, and electrocardiographic data were collected. There were no significant differences in age, sex, or type of heart disease between the groups. There were more patients in Group B vs. A who had ICDs implanted for secondary prevention (70.3 vs. 55.7%, P0.05). The mean QRS width was similar at implant but increased significantly in Group B vs. A on pre-ICD discharge electrocardiograms (134.1 ± 35.0 vs. 125.1 ± 36.2 ms, P0.05). Congestive heart failure class, comorbidities, use of antiarrhythmic agents, or left ventricular ejection fraction were not discriminators between Groups A and B.In this study of patients with long-standing ICDs, the only discriminating factors for appropriate shocks were implant for secondary prevention or increasing QRS width, suggesting electrical factors are the best predictors of ultimate ICD discharges.

The identification of patients with a diagnosis of seizure disorder who are also at risk for clinically significant bradycardia and/or tachycardia may require long-term cardiac rhythm monitoring. Noninvasive, continuous, outpatient cardiac rhythm monitoring may be useful for such clinical scenarios. The study group consisted of two male patients with a history of seizure disorder involving loss of consciousness. Clinical data and results of electrocardiography, echocardiography, electroencephelography, and continuous, mobile, outpatient cardiac rhythm monitoring are described. In the first patient, while cardiac bradyarrhythmias were secondary to seizures, sinus arrest most likely complicated the episodes by leading to more prolonged states of unconsciousness. In the second patient, permanent pacemaker implantation for AV block averted all clinical events previously attributed to seizures. Despite the different causal relationships between seizures and bradyarrhythmias in these two patients, mobile, cardiac outpatient telemetry was successful in diagnosing the contribution of cardiac dysrhythmia, leading to permanent pacemaker implantation. A diagnostic strategy that incorporates mobile, noninvasive, continuous, outpatient cardiac rhythm monitoring can effectively be utilized to diagnose significant seizure-related arrhythmias.

Sudden cardiac death is the most devastating complication of hypertrophic cardiomyopathy. Since HCM may present at young age, and since the risk period for sudden arrhythmic death may be long, decision-making in HCM patients may be difficult, and have lifelong implications. Community based studies show a sudden death mortality of approximately 1%/year. Certain patients can be identified by their clinical characteristics, and through testing, to have higher annual risk, as high as 4-5%/year. Risk factors sudden cardiac death include: family history of HCM and sudden death, recurrent syncope, ventricular tachycardia, as detected by Holter monitoring or exercise testing, subnormal (20 mmHg) increase in systolic blood pressure on maximal exercise testing and lastly marked (especially30 mm) left ventricular hypertrophy. The implantable defibrillator has been shown to avert sudden death in selected HCM patients deemed to be at high risk.

Background The Public Access Defibrillation (PAD) Trial was a randomized, controlled trial designed to measure survival to hospital discharge following out-of-hospital cardiac arrest (OOH-CA) in community facilities trained and equipped to provide PAD, compared with community facilities trained to provide cardiopulmonary resuscitation (CPR) without any capacity for defibrillation. Objectives To report the implementation of community-based lay responder emergency response programs in 1,260 participating facilities recruited for the PAD Trial in the United States and Canada. Methods This was a descriptive study of the characteristics of participating facilities, volunteers, and automated external defibrillator (AED) placements compiled by the PAD Trial, and a qualitative study of factors that facilitated or impeded implementation of emergency lay responder programs using focus groups of PAD Trial site coordinators. Results The PAD Trial enrolled 1,260 community facilities (14.8% residential), with 20,400 lay volunteers (mean +/- standard deviation = 13.4 +/- 10.7 per facility) trained to respond to OOH-CA. The 598 locations randomized to receive AEDs required 2.7 +/- 1.8 AEDs per facility. Volunteer attrition was high, 36% after two years. Barriers to recruitment and implementation included identification of appropriate "at-risk" facilities, lack of interest or fear of litigation by a facility key decision maker, lack of motivated potential volunteer responders, training and retraining resource requirements, and lack of an existing communication/response infrastructure. Conclusions These data indicate that implementation of community-based lay responder programs is feasible in many types of facilities, although these programs require substantial resources and commitment, and many barriers to implementation of effective PAD programs exist.

OBJECTIVES This study was designed to evaluate whether the destruction of the World Trade Center (WTC) on September 11, 2001 (9/11), led to an increased frequency of ventricular arrhythmias among patients fitted with an implantable cardioverter-defibrillator (ICD). BACKGROUND The WTC attack induced psychological distress. Because ICDs store all serious arrhythmias for months, the attack provided a unique opportunity to compare pre- and post-9/11 frequencies of potentially lethal arrhythmias among ICD patients. METHODS Two hundred consecutive ICD patients who presented for regularly scheduled follow-up to six affiliated clinics were recruited into this observational study. The electrograms stored in the ICDs for the three months before 9/11 and 13 months thereafter were scrutinized in a blinded manner (relative to date) for all ventricular tachyarrhythmias (tachycardia or fibrillation) triggering ICD therapy. RESULTS The frequency of tachyarrhythmias increased significantly for the 30 days post-9/11 (p = 0.004) relative to all other months between May 2001 and October 2002. In the 30 days post-9/11, 16 patients (8%) demonstrated tachyarrhythmias, compared with only seven (3.5%) in the preceding 30 days, representing a 2.3-fold increase in risk (95% confidence interval 1.1 to 4.9; p = 0.03). The first arrhythmic event did not occur for three days following 9/11, with events accumulating in a progressive non-clustered pattern. CONCLUSIONS Ventricular arrhythmias increased by more than twofold among ICD patients following the WTC attack. The delay in onset and the non-clustered pattern of these events differ sharply from effects following other disasters, suggesting that subacute stress may have served to promote this arrhythmogenesis.

CONTEXT: Implantable cardioverter defibrillator (ICD) therapy with backup ventricular pacing increases survival in patients with life-threatening ventricular arrhythmias. Most currently implanted ICD devices provide dual-chamber pacing therapy. The most common comorbid cause for mortality in this population is congestive heart failure. OBJECTIVE: To determine the efficacy of dual-chamber pacing compared with backup ventricular pacing in patients with standard indications for ICD implantation but without indications for antibradycardia pacing. DESIGN: The Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial, a single-blind, parallel-group, randomized clinical trial. SETTING AND PARTICIPANTS: A total of 506 patients with indications for ICD therapy were enrolled between October 2000 and September 2002 at 37 US centers. All patients had a left ventricular ejection fraction (LVEF) of 40% or less, no indication for antibradycardia pacemaker therapy, and no persistent atrial arrhythmias. INTERVENTIONS: All patients had an ICD with dual-chamber, rate-responsive pacing capability implanted. Patients were randomly assigned to have the ICDs programmed to ventricular backup pacing at 40/min (VVI-40; n = 256) or dual-chamber rate-responsive pacing at 70/min (DDDR-70; n = 250). Maximal tolerated medical therapy for left ventricular dysfunction, including angiotensin-converting enzyme inhibitors and beta-blockers, was prescribed to all patients. MAIN OUTCOME MEASURE: Composite end point of time to death or first hospitalization for congestive heart failure. RESULTS: One-year survival free of the composite end point was 83.9% for patients treated with VVI-40 compared with 73.3% for patients treated with DDDR-70 (relative hazard, 1.61; 95% confidence interval [CI], 1.06-2.44). The components of the composite end point, mortality of 6.5% for VVI-40 vs 10.1% for DDDR-70 (relative hazard, 1.61; 95% CI, 0.84-3.09) and hospitalization for congestive heart failure of 13.3% for VVI-40 vs 22.6% for DDDR-70 (relative hazard, 1.54; 95% CI, 0.97-2.46), also trended in favor of VVI-40 programming. CONCLUSION: For patients with standard indications for ICD therapy, no indication for cardiac pacing, and an LVEF of 40% or less, dual-chamber pacing offers no clinical advantage over ventricular backup pacing and may be detrimental by increasing the combined end point of death or hospitalization for heart failure.

Atrial fibrillation (AF) is a frequent event following cardiac surgery, occurring in up to 40% of patients [1-5]. The arrhythmia itself is often benign such that its occurrence is sometimes not labeled as a “complication” even so, postoperative AF is associated with an increased length of hospital stay following cardiac surgery. In addition, the sequellae of postoperative AF can be severe and even life-threatening including hemodynamic compromise and thromboemboli. As such, a thorough knowledge of the risk factors associated with the development of the arrhythmia is warranted. Furthermore, it is essential that this understanding include the underlying mechanisms by which these risk factors predispose, and to seek prevention and early treatment of postoperative AF.

The purpose of this study was to evaluate the signal processing and analysis methods currently in use for the P wave signal-averaged electrocardiogram and to define optimal parameters for its use. P wave signal-averaged electrocardiograms using the QRS as a trigger for alignment of the analysis window were obtained in 15 subjects with prior atrial fibrillation and 15 controls. Five methods of signal filtering (unidirectional, bidirectional, finite impulse response, least squares fit, and spectral fast-Fourier transform) and three filter frequencies (14, 29, and 60 Hz) were compared with logistic regression analysis. Analysis techniques, including P wave vector duration, individual orthogonal lead duration, and terminal root mean square voltage were also evaluated for the strength of their association with the occurrence of atrial fibrillation. The least-squares fit filter with bandwidth filtering of 29 to 250 Hz produced the strongest association with atrial fibrillation (odds ratio 26). A high correlation ( r > 0.92) was noted among the individual orthogonal leads; however, neither individual leads nor total atrial activation determined from individual leads demonstrated a superior association with atrial fibrillation when compared with total vector P wave duration. Terminal P wave RMS voltages were not significantly different between patients with prior AF and controls. (Am Heart J 1997;134:985-93.)

In a recent prospective study, we had identified prolonged p-wave duration on signal-averaged (SA) ECG as a predictor of atrial fibrillation (AF) after cardiac surgery. Although several clinical characteristics have also predicted AF, the results have been inconsistent. The purpose of the present study was to examine a variety of clinical, surgical and laboratory parameters to establish accurate risk factors, and to gain insight into the mechanism, of AF in this setting. 272 consecutive patients undergoing elective cardiac surgery were enrolled. clinical data collected and pre-op p-wave SAECG recorded. Patients were observed after cardiac surgery for the development of AF. During the period of observation, 79 of the 272 patients (29%) developed AF 2.5 ± 1.7 days (range of 1 – 8 days) after surgery. 22 variables were analyzed and univariate predictors of AF were identified: EF l 40%, valve surgery, pre-op use of digoxin, p-wave SAECG and p-wave on SAECG g 140 msec. Prior MI, HTN, pre-op use of beta blockers, aortic cross clamp time were not predictive. Multivariate analysis demonstrated that p-wave SAECG and low EF were significant independent predictors of AF. P-wave duration on SAECG g 140 msec and EF l 40% were associated with relative risks of 3.1 and 2.8, respectively. P-wave SAECG was the most sensitive test, identifying 82% of patients who experienced AF. Conclusion AF continues to be a common complication after cardiac surgery. The presence of pre-op anatomic and electrophysiologic abnormalities promote AF, and clinical variables can be used to identify those at greatest risk.

Transient left atrial (LA) dysfunction (“stunning”) and the appearance of spontaneous echo contrast (“smoke”) have been reported in patients undergoing DC cardioversion of atrial fibrillation. It has been suggested that cardioversion-induced LA dysfunction may promote new thrombus formation leading to thromboembolic complications in AF patients even in the absence of demonstrable LA thrombus prior to cardioversion. In order to confirm previous observations of LA stunning end to investigate the determina nts of this response, we investigated LA function in a series of patients undergoing implantable defibrillator insertion and testing. Eight patients (67 ± 6 yrs, 5 M/3 F) with ischemic heart disease (n = 6) or cardiomyopathy (n = 2) and VTNF were studied. All patients were in NSR, had significant impairment of systolic LV function, and demonstrated inducible VT or VF in the EP lab. Intraoperative transesophegeal echocardiography with a biplane or multiplane probe was used to image the LA, mitral valve and LA appendage (LAA). Blood flow velocities were measured at the tips of the MV leaflets and LAA orifice by pulsed-wave Doppler before and 30 to 120 seconds after DC shocks of 15–20 joules with transvenous intracardiac electrodes lin SVC and RV apex, n = 7) or epicardial patches (n = 1) while in sinus rhythm. Measurements from three different cardiac cycles were averaged for each patient. Baseline LAA orifice flow velocity was 44 ± 16 cm/s and remained unchanged after DC shock, 46 ± 20 cm/s (p = ns). Similarly, MV peak A-wave velocity was 70 ± 34 cm/s at baseline and was not significantly different after DC shock, 69 ± 42 cm/s (p = ns). No evidence of LA “smoke” was seen in any patient before or after the shock. Conclusion As opposed to previous reports after cardioversion of atrial fibrillation, DC shocks alone do not produce LA dysfunction in patients in NSR even in the presence of left venticular dysfunction. LA stunning after DC shocks may require prior atrial fibrillation or specific atrial substrate.