Deepak Bhakta

Electrocardiographic Abnormalities and Sudden Death in Myotonic Dystrophy Type 1

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.)

Thoracic Spinal Cord Stimulation Reduces the Risk of Ischemic Ventricular Arrhythmias in a Postinfarction Heart Failure Canine Model

Background—Thoracic spinal cord stimulation (SCS) is a promising therapy in treating refractory angina. This study was designed to investigate SCS with regard to the risk of arrhythmias during myocardial ischemia and its cardiac electrophysiological effects. Methods and Results—We studied 22 dogs with healed anterior myocardial infarction (MI) and superimposed heart failure (HF) induced by rapid ventricular pacing. SCS was applied at the dorsal T1–T2 segments of the spinal cord (at 50 Hz, 0.2 ms) for 15 minutes. Transient (2-minute) myocardial ischemia was induced on 2 separate occasions (no SCS and SCS) to provoke ventricular arrhythmias (ventricular tachycardia/ventricular fibrillation; VT/VF). Ischemic episodes were separated by 90 minutes, and dogs were randomly assigned to receive SCS or no SCS before the first or second ischemic episode. SCS reduced the occurrence of VT/VF from 59% to 23% when SCS was applied during transient myocardial ischemia (odds ratio, 0.36; 95% confidence interval, 0.1626 to 0.5646; P=0.0009). SCS also decreased sinus rate by 7.5±14 bpm (P=0.048), increased the PR interval by 11.1±14.7 ms (P=0.009), and reduced systolic blood pressure by 9.8±13.6 mm Hg (P=0.02). Conclusions—Thoracic SCS appears to protect against ischemic VT/VF in a canine model of healed MI and HF. SCS reduced sinus rate and systolic blood pressure, changes consistent with the previously known antisympathetic effect of SCS, which may have contributed to the antiarrhythmic benefits.

Management and outcomes of cardiac tamponade during atrial fibrillation ablation in the presence of therapeutic anticoagulation with warfarin

BACKGROUND Cardiac tamponade (CT) is a possible complication of radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF). Although the incidence of CT is not higher when RFCA is performed with a therapeutic international normalized ratio (INR), outcomes of CT are unclear. OBJECTIVE We compared outcomes among patients with and without a therapeutic INR who developed CT as a complication of RFCA of AF. METHODS The subjects of this retrospective study were 40 consecutive patients who developed CT during RFCA of AF at 3 centers. We divided the patients into 2 groups: RFCA performed with INR < 2 (group 1) and INR ≥ 2 (group 2). There were 23 patients in group 1 and 17 patients in group 2. RESULTS Baseline clinical and procedure characteristics were not different between the 2 groups. Heparin was reversed by protamine in 83% and 94% of patients (P = .37), and warfarin was reversed by fresh frozen plasma or factor VIIa in 17% and 35% of patients (P = .27) in groups 1 and 2, respectively. All patients were successfully treated by percutaneous drainage, and none required surgical intervention. There were no significant differences in the amount of initial pericardial drainage (523 ± 349 ml vs. 409 ± 157 ml, P = .22) or the duration of drainage (P = .14) between the 2 groups. All patients survived to hospital discharge. Median length of hospital stay was 2 days longer in group 1 (P <.01). CONCLUSION Cardiac tamponade is not more severe or difficult to manage in the presence of therapeutic anticoagulation with warfarin in patients undergoing RFCA of AF.

Increased mortality with left ventricular systolic dysfunction and heart failure in adults with myotonic dystrophy type 1.

BACKGROUND Myotonic dystrophy type 1 (DM1) is a neurologic disorder with known cardiac involvement, including left ventricular systolic dysfunction (LVSD), heart failure (HF), atrioventricular and intraventricular conduction system disease, and sudden death. We studied the prevalence of these conditions and associated findings in a large population with DM1. METHODS History, physical examination, genetic testing, and electrocardiography were performed on 406 patients with DM1, and cardiac imaging was performed on 180 (44.3%) of these patients. RESULTS Left ventricular systolic dysfunction and clinical HF were found in 34 (18.9%) of 180 and in 23 (5.7%) of 406 of enrolled subjects, respectively, yielding an overall prevalence of LVSD/HF in 41 (10.1%) of 406. Increasing age, male sex, electrocardiographic conduction abnormalities, presence of atrial and ventricular arrhythmias, and implanted devices were all significantly associated with LVSD/HF, whereas cytosine-thiamine-guanine repeat length and neuromuscular severity score were not. The interval≥240 milliseconds (relative risk 4.1, 95% CI 1.7-9.6, P=.001) and QRS duration≥120 milliseconds (relative risk 4.2, 95% CI 2.0-8.5, P<.001) were significant predictors of LVSD/HF. The presence of LVSD/HF was also significantly associated with all-cause death (relative risk 3.9, 95% CI 2.3-6.4, P<.001) and cardiac death (relative risk 5.7, 95% CI 2.6-12.4, P<.001). CONCLUSIONS A significant prevalence of LVSD/HF exists in patients with DM1. The presence of LVSD/HF in DM1 is significantly associated with all-cause and cardiac death.

A retrospective analysis of proceduralist-directed, nurse-administered propofol sedation for implantable cardioverter-defibrillator procedures

BACKGROUND There is controversy whether proceduralist-directed, nurse-administered propofol sedation (PDNAPS) is safe. OBJECTIVE To assess the frequency of adverse events when PDNAPS is used for implantable cardioverter-defibrillator (ICD)-related procedures and to determine the patient and procedural characteristics associated with adverse events. METHODS Consecutive ICD-related procedures using PDNAPS from May 2006 to July 2009 at a tertiary-care hospital were evaluated. Serious adverse events were defined as procedural death, unexpected transfer to an intensive care unit, respiratory failure requiring intubation/bag-mask ventilation, or hypotension requiring vasoconstrictor/inotrope support. Nonserious adverse events were defined as hypotension requiring fluid resuscitation or hypoxemia requiring augmented respiratory support with non-rebreather mask, oral airway, or jaw lift. RESULTS Of 582 patients (age 64 ± 14 years, 72.3% males) undergoing ICD-related procedures using PDNAPS, 58 (10.0%) patients had serious adverse events with no procedural death and 225 (38.7%) had nonserious adverse events. Longer procedure duration (relative risk [RR] = 2.1 per hour; 95% confidence interval [CI] = 1.6-2.8; P < .001) and biventricular implant (RR = 2.7; CI = 1.4-5.3; P = .003) were independent predictors of serious adverse events. A longer procedure duration (RR = 1.4 per hour; CI = 1.1-1.7; P = .001), heart failure class (RR = 1.4 per 1 class; CI = 1.1-1.7; P = .002), and use of propofol infusion (RR = 3.5; CI = 2.2-5.7; P < .001) were independent predictors of nonserious adverse events. CONCLUSION PDNAPS for shorter ICD procedures including single- and dual-chamber implants, generator changes, and defibrillation threshold testing have acceptable rates of serious adverse events and manageable nonserious adverse events and should be considered for further study. Biventricular implants and other complex procedures should be done with an anesthesiologist.

Heart rate variability declines with increasing age and CTG repeat length in patients with myotonic dystrophy type 1

Background: Cardiac myopathy manifesting as arrhythmias is common in the neurological disease, myotonic dystrophy type 1 (DM1). The purpose of the present study was to evaluate heart rate variability (HRV) in patients with DM1.

Dysfunction in the βII Spectrin–Dependent Cytoskeleton Underlies Human Arrhythmia

Background— The cardiac cytoskeleton plays key roles in maintaining myocyte structural integrity in health and disease. In fact, human mutations in cardiac cytoskeletal elements are tightly linked to cardiac pathologies, including myopathies, aortopathies, and dystrophies. Conversely, the link between cytoskeletal protein dysfunction and cardiac electric activity is not well understood and often overlooked in the cardiac arrhythmia field. Methods and Results— Here, we uncover a new mechanism for the regulation of cardiac membrane excitability. We report that &bgr;II spectrin, an actin-associated molecule, is essential for the posttranslational targeting and localization of critical membrane proteins in heart. &bgr;II spectrin recruits ankyrin-B to the cardiac dyad, and a novel human mutation in the ankyrin-B gene disrupts the ankyrin-B/&bgr;II spectrin interaction, leading to severe human arrhythmia phenotypes. Mice lacking cardiac &bgr;II spectrin display lethal arrhythmias, aberrant electric and calcium handling phenotypes, and abnormal expression/localization of cardiac membrane proteins. Mechanistically, &bgr;II spectrin regulates the localization of cytoskeletal and plasma membrane/sarcoplasmic reticulum protein complexes, including the Na/Ca exchanger, ryanodine receptor 2, ankyrin-B, actin, and &agr;II spectrin. Finally, we observe accelerated heart failure phenotypes in &bgr;II spectrin–deficient mice. Conclusions— Our findings identify &bgr;II spectrin as critical for normal myocyte electric activity, link this molecule to human disease, and provide new insight into the mechanisms underlying cardiac myocyte biology.

Multivessel coronary thrombosis secondary to cocaine use successfully treated with multivessel primary angioplasty

Cocaine use has been associated with a significant risk of myocardial ischemia and myocardial infarction (MI).1– 2 The previous approach to the treatment of cocaine‐induced MI focused on medical treatment with verapamil, nitroglycerine and thrombolytics. Percutaneous revascularization for the cocaine‐associated MI has been reported and is the preferred treatment modality.3 Identification of culprit vessel in the patients presenting with acute myocardial infarction associated with cocaine use is problematic owing to the frequent presence of baseline electrocardiogram (ECG) changes. Chronic cocaine use predisposes to diffuse coronary vasculopathy and may cause systemic alteration of coagulation parameters. Multivessel coronary thrombosis presenting as myocardial infarction associated with cocaine use has not been previously reported. This study describes a case of multivessel coronary thrombosis caused by cocaine ingestion successfully treated with multivessel primary angioplasty. (Int J Cardiovasc Intervent 2004; 1: 39–42)

Familial clustering of muscular and cardiac involvement in myotonic dystrophy type 1.

Myotonic dystrophy type 1 (DM1) is associated with both skeletal and cardiac muscle involvement. The aim of the present study was to determine whether familial clustering is observed in the severity of muscle involvement in DM1. We evaluated 51 sibling groups constituting 112 patients with genetically‐verified DM1. The siblings were similar to each other in age, cytosine‐thymine‐guanine (CTG) repeat length, age at disease onset, muscular impairment rating score, and electrocardiographic markers of cardiac conduction disease. After adjusting for the similarities between siblings in age and CTG repeat length, the siblings remained similar to each other in measures of both skeletal and cardiac muscle involvement. These results suggest that factors other than CTG repeat length play a role in the severity and progression of the degenerative skeletal and cardiac muscle disease in DM1. Muscle Nerve, 2005

Arrhythmia exacerbation after sodium channel blockade in myotonic dystrophy type 1

Cardiac conduction abnormalities manifesting as arrhythmias are common in myotonic dystrophy type 1 (DM1). Up to one-third of DM1 patients die suddenly from arrhythmias. Sodium channel blockers have been used in DM1 patients to treat myotonia. We report a DM1 patient who received a sodium channel blocker that exacerbated an arrhythmia. A 32-year-old man was referred for cardiac risk assessment. He was diagnosed with DM1 3 years previously based on clinical myotonia and a clinical and genetic diagnosis of DM1 in first-degree relatives. Family history was pertinent for a brother, age 34, who had ventricular tachycardia attributed to DM1 and had received an implantable cardioverter-defibrillator (ICD). Examination revealed no muscle weakness or atrophy, but grip myotonia was present. The electrocardiogram (ECG) showed a PR interval of 195 ms (normal 120–200 ms) and QRS duration of 118 ms (normal 60–100 ms) with an incomplete right bundle branch block. A 24-h ambulatory ECG revealed asymptomatic sinus bradycardia and pauses. An echocardiogram was normal. Given the family history and the abnormal ECGs, a cardiac electrophysiology study was done to assess for arrhythmias. Intracardiac catheters were placed to pace and record the atrial, His bundle, and ventricular ECGs. The interval from the His bundle to the QRS complex, the His-ventricular (HV) interval, was prolonged at 65 ms (normal 40–55 ms) indicative of a distal conduction abnormality. No other abnormalities were found, and no arrhythmias were induced during a drug-free study and after beta-adrenergic stimulation with isoproterenol. The patient received procainamide 1,000 mg (10 mg/ kg) intravenously to stress cardiac conduction and potentially unmask latent arrhythmias. Plasma concentrations at 30 min after the infusion were procainamide 4.5 lg/ml (therapeutic 4–10 lg/ml) and the active metabolite, nacetyl procainamide < 1.0 lg/ml (therapeutic 10–20 lg/ ml) consistent with an acute therapeutic load. Grip myotonia was absent on testing. Intracardiac recordings revealed only a slight further prolongation in the HV interval to 70 ms. During ventricular pacing, a sustained polymorphic ventricular tachycardia/fibrillation was initiated (Fig. 1). The patient lost consciousness and required defibrillation. The tachycardia was believed to be clinically relevant and indicative of a high risk of future spontaneous arrhythmias. He received an ICD. Myotonia, a delayed muscle relaxation after contraction, is a core feature of DM1. The myotonia results from a decrease in both the number and function of sarcolemmal chloride channels. Pharmacological agents that block the sodium channel are the most common class of drugs evaluated to treat myotonia. They work by inhibiting the skeletal muscle fast sodium channel, decreasing the likelihood of repetitive action potentials. Agents that have been evaluated include quinine, procainamide, disopyramide, tocainide, mexiletine, and N-propyl-ajmalin. In small studies, these agents improve subjective and objective myotonia. In our patient, grip myotonia was no longer observed after procainamide. A Cochrane review concluded that it is impossible to determine whether drug treatment of myotonia is effective or safe because of the lack of high-quality studies. Our letter is intended to comment on the risk of using sodium channel blockers in DM1 patients. All of these agents, as a class effect, also inhibit the myocardial fast sodium channel, a key determinant of cardiac conduction. By slowing cardiac conduction, these agents can worsen the abnormalities already present in the DM1 heart. The result is a patient at greater likelihood for life-threatening arrhythmias including those causing sudden death.