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The article presents a study which evaluated mortality in relation to genotype in a large cohort of patients with myotonic dystrophy type 1 (DM1). DM1 is an autosomal dominant disease triggered by a widened trinucleotide cytosine-thymine-guanine repeat. The subjects used were acquired from 23 neuromuscular disease clinics in the U.S. The conclusion was that premature mortality related to respiratory and cardiac causes was analyzed in a general, adult DM1 population.

William J. Groh, Deepak Bhakta and Robert M. Pascuzzi respond to a letter to the editor about their article "Electrocardiographic Abnormalities and Sudden Death in Myotonic Dystrophy" in the June 19, 2008 issue.

Background: Sudden death can occur as a consequence of cardiac-conduction abnormalities in the neuromuscular disease myotonic dystrophy type 1. The determinants of the risk of sudden death remain imprecise. Methods: We assessed whether the electrocardiogram (ECG) was useful in predicting sudden death in 406 adult patients with genetically confirmed myotonic dystrophy type 1. A patient was characterized as having a severe abnormality if the ECG had at least one of the following features: rhythm other than sinus, PR interval of 240 msec or more, QRS duration of 120 msec or more, or second-degree or third-degree atrioventricular block. Results: Patients with severe abnormalities according to the entry ECG were older than patients without severe abnormalities, had more severe skeletal-muscle impairment, and were more likely to have heart failure, left ventricular systolic dysfunction, or atrial tachyarrhythmia. Such patients were more likely to receive a pacemaker or an implantable cardioverter–defibrillator during the follow-up period. During a mean follow-up period of 5.7 years, 81 patients died; there were 27 sudden deaths, 32 deaths from progressive neuromuscular respiratory failure, 5 nonsudden deaths from cardiac causes, and 17 deaths from other causes. Among the 17 patients who died suddenly in whom postcollapse rhythm was evaluated, a ventricular tachyarrhythmia was observed in 9. A severe ECG abnormality (relative risk, 3.30; 95% confidence interval [CI], 1.24 to 8.78) and a clinical diagnosis of atrial tachyarrhythmia (relative risk, 5.18; 95% CI, 2.28 to 11.77) were independent risk factors for sudden death. Conclusions: Patients with adult myotonic dystrophy type 1 are at high risk for arrhythmias and sudden death. A severe abnormality on the ECG and a diagnosis of an atrial tachyarrhythmia predict sudden death. (ClinicalTrials.gov number, NCT00622453.) N Engl J Med 2008;358:2688-97. [ABSTRACT FROM AUTHOR]

Summary: Objectives: To evaluate the characteristics of volunteers responding to emergencies in the North American Public Access Defibrillation (PAD) Trial. Methods: The PAD Trial was a prospective evaluation of cardiac arrest survival in community facilities randomized to cardiopulmonary resuscitation (CPR) or to CPR with automated external defibrillators (AEDs). The PAD volunteers’ characteristics were analyzed using Poisson regression clustered on the facility and offset by the number of emergency episodes to which volunteers were exposed. Results: A total of 19,320 volunteers in 1260 facilities were trained to provide emergency care. Of these, 8169 volunteers were participating actively at their facility during a time when one or more emergency episodes occurred. There were 1971 emergency episodes responded to by 1245 volunteers. The treatment arm (CPR-only versus CPR+AED) was not associated with the likelihood of volunteer participation in an episode. Likewise, the volunteers’ age or sex did not affect response. Volunteers more likely to respond were supervisory/management or security personnel, non-minority participants, volunteers with previous CPR training, volunteers with previous experience in emergency care and those who passed the PAD CPR skills follow-up test. Volunteers who had a formal education beyond a high school level were less likely to respond. Conclusions: Volunteers with previous emergency training and positions of responsibility in their facility had a greater likelihood of participation in medical emergencies in the PAD Trial. [Copyright &y& Elsevier]

Evaluates the use of implantable cardioverter-defibrillators in patients with the long QT syndrome. Consideration of death as sudden cardiac death; Presence in the patients of an echocardiogram or cardiac catheterization; Absence in the patients of structural heart disease.

Evaluates the quality of life of patients with implantable cardioverter-defibrillators (ICD) in the U.S. Impact of ICD therapy; Measurement of health-related quality of life; Factors driving decisions regarding ICD therapy.

A letter to the editor is presented in response to the article "Electrophysiological study with prophylactic pacing and survival in adults with myotonic dystrophy and conduction system disease" by Wahbi K. and colleagues in the 2012 issue along with a reply from the authors to the same.

A letter to the editor is presented in response to the article "Use of Automated External Defibrillators by a U.S. Airline," by R.L. Page, J.A. Joglar and colleagues in the October 26, 2000 issue.

A letter to the editor is presented in response to the article "Cardiopulmonary Resuscitation by Chest Compression Alone or With Mouth-to-Mouth Ventilation," by A. Hallstrom, L. Cobb and colleagues in the May 25, 2000 issue.

Summary: The adverse event (AE) profile of lay volunteer CPR and public access defibrillation (PAD) programs is unknown. We undertook to investigate the frequency, severity, and type of AE''s occurring in widespread PAD implementation. Design: A randomized-controlled clinical trial. Setting: One thousand two hundred and sixty public and residential facilities in the US and Canada. Participants: On-site, volunteer, lay personnel trained in CPR only compared to CPR plus automated external defibrillators (AEDs). Intervention: Persons experiencing possible cardiac arrest receiving lay volunteer first response with CPR+AED compared with CPR alone. Main outcome measure: An AE is defined as an event of significance that caused, or had the potential to cause, harm to a patient or volunteer, or a criminal act. AE data were collected prospectively. Results: Twenty thousand three hundred and ninety six lay volunteers were trained in either CPR or CPR+AED. One thousand seven hundred and sixteen AEDs were placed in units randomized to the AED arm. There were 26,389 exposure months. Only 36 AE''s were reported. There were two patient-related AEs: both patients experienced rib fractures. There were seven volunteer-related AE''s: one had a muscle pull, four experienced significant emotional distress and two reported pressure by their employee to participate. There were 27 AED-related AEs: 17 episodes of theft involving 20 devices, three involved AEDs that were placed in locations inaccessible to the volunteer, four AEDs had mechanical problems not affecting patient safety, and three devices were improperly maintained by the facility. There were no inappropriate shocks and no failures to shock when indicated (95% upper bound for probability of inappropriate shock or failure to shock=0.0012). Conclusions: AED use following widespread training of lay-persons in CPR and AED is generally safe for the volunteer and the patient. Lay volunteers may report significant, usually transient, emotional stress following response to a potential cardiac arrest. Within the context of this prospective, randomized multi-center study, AEDs have an exceptionally high safety profile when used by trained lay responders. [Copyright &y& Elsevier]

Background: The etiology of conduction disturbances necessitating permanent pacemaker (PPM) implantation is often unknown, although familial aggregation of PPM (faPPM) suggests a possible genetic basis. We developed a pan-cardiovascular next generation sequencing (NGS) panel to genetically characterize a selected cohort of faPPM. Materials and Methods: We designed and validated a custom NGS panel targeting the coding and splicing regions of 246 genes with involvement in cardiac pathogenicity. We enrolled 112 PPM patients and selected nine (8%) with faPPM to be analyzed by NGS. Results: Our NGS panel covers 95% of the intended target with an average of 229x read depth at a minimum of 15-fold depth, reaching a SNP true positive rate of 98%. The faPPM patients presented with isolated cardiac conduction disease (ICCD) or sick sinus syndrome (SSS) without overt structural heart disease or identifiable secondary etiology. Three patients (33.3%) had heterozygous deleterious variants previously reported in autosomal dominant cardiac diseases including CCD: LDB3 (p.D117N) and TRPM4 (p.G844D) variants in patient 4; TRPM4 (p.G844D) and ABCC9 (p.V734I) variants in patient 6; and SCN5A (p.T220I) and APOB (p.R3527Q) variants in patient 7. Conclusion: FaPPM occurred in 8% of our PPM clinic population. The employment of massive parallel sequencing for a large selected panel of cardiovascular genes identified a high percentage (33.3%) of the faPPM patients with deleterious variants previously reported in autosomal dominant cardiac diseases, suggesting that genetic variants may play a role in faPPM. [ABSTRACT FROM AUTHOR]

Pacemakers and ICDs in Myotonic Dystrophy. Introduction: We assessed implant rates, indications, characteristics, and outcomes in patients with the neuromuscular disease, myotonic dystrophy type 1 (DM1) receiving a pacemaker or an implantable cardioverter-defibrillator (ICD). Methods and Results: Device use was evaluated in a prospective, multicenter registry of 406 genetically confirmed adult patients followed for 9.5 ± 3.2 years. Forty-six (11.3%) had or received a pacemaker and 21 (5.2%) received an ICD. Devices were primarily implanted for asymptomatic conduction abnormalities and left ventricular (LV) systolic dysfunction. However, 7 (15.2%) pacemakers were implanted for third-degree atrioventricular block and 6 (28.6%) ICDs were implanted for ventricular tachyarrhythmias (ventricular tachycardia [VT] or fibrillation [VF]). Patients receiving devices were older and more frequently had heart failure, LV systolic dysfunction, atrial tachyarrhythmias, and ECG conduction abnormalities compared to nondevice patients. Five (10.9%) pacemaker patients underwent upgrade to an ICD, 3 for LV systolic dysfunction, 1 for VT/VF, and 1 for progressive conduction disease. Seventeen (27.4%) of the 62 patients with devices were pacemaker-dependent at last follow-up. Three (14.3%) ICD patients had appropriate therapies. Twenty-four (52.2%) pacemaker patients died including 13 of respiratory failure and 7 of sudden death. Seven (33.3%) ICD patients died including 2 of respiratory failure and 3 of sudden death. The patients with ICDs and sudden death all had LV systolic dysfunction and 1 death was documented due to inappropriate therapies. Conclusions: DM1 patients commonly receive antiarrhythmia devices. The risk of VT/VF and sudden death suggests that ICDs rather than pacemakers should be considered for these patients. (J Cardiovasc Electrophysiol, Vol. 22, pp. 1369-1375, December 2011) [ABSTRACT FROM AUTHOR]

Reliable, valid measures are needed to assess one's sense of mastery, which has the potential for decreasing anxiety and depressive symptoms among patients with implantable cardioverter-defibrillators (ICDs). This study evaluates the reliability and validity of a measure of mastery, the Chronic Heart Failure Questionnaire (CHQ) mastery subscale. One hundred twentytwo (75% men, mean age 65 years) and 100 patients complete baseline and 12-month face-to-face interviews, respectively. The CHQ mastery subscale is found to have internal consistency reliability (Cronbach's alphas = .79, .84), and its validity is supported. Factor analysis yields a single robust factor. Differences in the CHQ mastery subscale scores by the New York Heart Association (NYHA) classes are found: Patients with NYHA Class III or IV have lower mastery than those with Class I or II. Baseline younger age and less frequent ICD shocks and lower mastery are significant predictors of respectively 12-month anxiety (R² = .37) and depressive symptoms (R² = .45). The CHQ mastery subscale has demonstrated satisfactory reliability and validity in this sample. [ABSTRACT FROM AUTHOR]

Abstract: The high-affinity choline transporter (CHT1) system is an attractive target for the development of positron emission tomography (PET) biomarkers to probe brain, cardiac, and cancer diseases. An efficient and convenient synthesis of new radiolabeled CHT1 inhibitors [11C]hemicholinium-3 and [18F]hemicholinium-3 by solid-phase extraction (SPE) technique using a cation-exchange CM Sep-Pak cartridge has been well developed. The preliminary evaluation of both tracers through biodistribution studies in 9L-glioma rats has been performed, and the uptakes in the heart and tumor were observed, while very low brain uptake was seen. [Copyright &y& Elsevier]

Abstract: [11C]Hemicholinium-15 ([11C]HC-15) and [18F]hemicholinium-15 ([18F]HC-15) have been synthesized as new potential PET tracers for the heart high-affinity choline uptake (HACU) system. [11C]HC-15 was prepared by N-[11C]methylation of the appropriate precursor, 4-methyl-2-phenyl-morpholin-2-ol, using [11C]CH3OTf in 55–70% radiochemical yield decay corrected to end of bombardment (EOB) and 2–3Ci/μmol specific activity at end of synthesis (EOS). [18F]HC-15 was prepared by N-[18F]fluoromethylation of the precursor using [18F]FCH2OTf in 20–30% radiochemical yield decay corrected to EOB and >1.0Ci/μmol specific activity at EOS. The biodistribution of both compounds was determined in rats at 20min post-intravenous injection, and the results show the heart region uptakes 1.32±0.75%ID/g in R-ventricle for [11C]HC-15 and 1.28±0.81%ID/g in L-ventricle for [18F]HC-15, respectively. The dynamic PET imaging studies of [11C]HC-15 in rats were acquired 60min post-intravenous injection of the tracer using the IndyPET-II scanner. For the blocking experiments, the rats were intravenously pretreated with 3.0mg/kg of unlabeled HC-15 prior to [11C]HC-15 injection. [11C]HC-15 rat heart PET studies show rapid heart uptake to give clear heart images. The rat heart PET blocking studies found no significant blocking effect. The dynamic PET studies in normal and ablated dogs were performed using Siemens PET scanner with [13N]NH3, [11C]HC-15, and [18F]HC-15. PET studies in dogs of both [11C]HC-15 and [18F]HC-15 also show significant heart uptake and give images of the heart. However, there is no significant change in [11C]HC-15 L-ventricle uptake following radiofrequency ablation in the dog. These results suggest that the localization of HC-15 tracers in the heart is mediated by non-specific processes, and the visualization of HC-15 tracers on the heart is related to non-specific binding of HACU. [Copyright &y& Elsevier]

Despite substantial progress in the diagnosis and treatment of acute ST-segment elevation myocardial infarction (STEMI), implementation of this knowledge into routine clinical practice has been variable. It has become increasing clear that primary percutaneous coronary intervention (PCI) is the preferred method of reperfusion if it can be performed in a timely manner. Recent European data suggest that transfer for direct PCI may also be preferable to fibrinolytic therapy. We believe it is time to establish a national policy for treatment of patients with STEMI to develop a coordinated system of care similar to that of the level 1 trauma system. [Copyright &y& Elsevier]

Abstract: A new AChE tracer N-[11C]methyl-3-[[(dimethylamino)carbonyl]oxy]-2-(2′,2′-diphenylpropionoxymethyl)pyridinium ([11C]MDDP, [11C]1) has been synthesized in 40–65% radiochemical yield. Initial PET dynamic studies of [11C]MDDP in rat heart showed rapid heart uptake and blood pool clearance to give high-quality heart images. Blocking studies of [11C]MDDP with pretreatment drug neostigmine in rats found only minor reductions in rat heart [11C]MDDP retention. The results suggest that [11C]MDDP delineates the heart very clearly, and the uptakes of [11C]MDDP in rat heart might be related to non-specific binding. [Copyright &y& Elsevier]

A series of 11C-labeled analogs of the acetylcholinesterase (AChE) inhibitor pyridostigmine have been synthesized for evaluation as new potential positron emission tomography (PET) imaging agents for heart AChE. The appropriate precursors for radiolabeling were slightly modified from commercial reagents. The new tracers [11C]pyridostigmine (1), [11C]para-pyridostigmine (2) and [11C]ortho-pyridostigmine (3) were prepared by N-[11C]methylation of the precursors using [11C]methyl triflate. Pure target compounds were isolated by a solid-phase extraction (SPE) purification procedure with 60–85% radiochemical yields (decay corrected to end of bombardment), and a synthesis time of 10–15 min. The initial PET dynamic studies of compounds (1–3) in rat heart showed rapid heart uptake and blood pool clearance to give high quality heart images. These results suggest the new tracers delineate the heart very clearly and could be potential heart AChE imaging agents. [Copyright &y& Elsevier]

Background: Measuring survival from sudden out-of-hospital cardiac arrest (OOH-CA) is often used as a benchmark of the quality of a community’s emergency medical service (EMS) system. The definition of OOH-CA survival rates depends both upon the numerator (surviving cases) and the denominator (all cases). Purpose: The purpose of the public access defibrillation (PAD) trial was to measure the impact on survival of adding an automated external defibrillator (AED) to a volunteer response system trained in CPR. This paper reports the definition of OOH-CA developed by the PAD trial investigators, and it evaluates alternative statistical methods used to assess differences in reported “survival.” Methods: Case surveillance was limited to the prospectively determined geographic boundaries of the participating trial units. The numerator in calculating a survival rate should include only those patients who survived an event but who otherwise would have died except for the application of some facet of emergency medical care—in this trial a defibrillatory shock. Among denominators considered were: total population of the study unit, all deaths within the study unit, and documented ventricular fibrillation cardiac arrests. The PAD classification focused upon cases that might have benefited from the early use of an AED, in addition to the likely benefit from early recognition of OOH-CA, early access of EMS, and early cardiopulmonary resuscitation (CPR). Results of this classification system were used to evaluate the impact of the PAD definition on the distribution of cardiac arrest case types between CPR only and CPR + AED units. Results: Potential OOH-CA episodes were classified into one of four groups: definite, probable, uncertain, or not an OOH-CA. About half of cardiac arrests in the PAD units were judged to be definite OOH-CA events and therefore potentially treatable with an AED. However, events that occurred in CPR-only units were less likely to be classified as definite or probable OOH-CA events than those in CPR + AED units (43% versus 55%, odds ratio 0.78, 95% confidence interval 0.57–1.07). The study retained sufficient power to permit a statistical analysis of the alternative hypothesis that the CPR + AED method results in twice as many survivors as a CPR-only approach. The result is critically dependent on the denominator used for calculating survival rates; but the analysis does not require a denominator as the numerators will have identical Poisson distributions (counts for rare events) under the null hypothesis since randomization distributes the risk of cardiac arrest evenly between the two arms. Conclusion: Reported OOH-CA rates and survival rates vary widely, depending upon the definitions applied to events. Rigorous assessment of treatments applied to improve survival can be obscured by inappropriate definitions. Large-scale randomized interventions designed to improve survival from OOH-CA can be evaluated based upon the absolute numbers of patients surviving, rather than a change in the proportion surviving. [Copyright &y& Elsevier]

Induction of Monomorphic Ventricular Tachycardia. We report the case of a patient in whom transvenous left ventricular pacing lead placement at the time of a biventricular upgrade led to an exacerbation of clinical monomorphic ventricular tachycardia (MVT). At implant, slow left ventricular pacing repeatedly induced sustained MVT. However, testing of the biventricular pacing showed no MVT inducibility, and the system was implanted. The patient was readmitted due to multiple episodes of the MVT observed at implant. The MVT was controlled with pharmacotherapy, allowing the patient to continue with biventricular pacing. (J Cardiovasc Electrophysiol, Vol. 14, pp. 1245-1247, November 2003) [ABSTRACT FROM AUTHOR]