Baseline myocardial perfusion predicts response to cardiac resynchronization therapy: a prospective observational study.

PURPOSE: We prospectively determined whether preimplant myocardial perfusion imaging (MPI) predicts outcome with biventricular pacing (BiVP). METHODS: Single-photon emission computed tomography (SPECT) MPI, left ventricular (LV) volumes, ejection fraction (EF), 6-min hall walk (6MW) were assessed at baseline and at 4 months in 19 patients with ischemic cardiomyopathy undergoing BiVP. Clinical and hemodynamic responses were correlated with MPI. RESULTS: Lower global myocardial scar burden predicted hemodynamic response to BiVP, while higher burden was associated with poor response. Clinical improvement with BiVP occurred in 12 (63%) of the patients. Clinical BiVP responders had lower rest/stress MPI score difference. There was a close negative correlation between MPI reversibility and increased 6MW distance. CONCLUSIONS: Baseline MPI is associated with clinical and hemodynamic response to BiVP: greater myocardial scar burden is predictive of poor hemodynamic response, while higher ischemic burden is predictive of poor clinical response. There is a differential response to BiVP by clinical and hemodynamic criteria.

Pericardial delivery of omega-3 fatty acid: a novel approach to reducing myocardial infarct sizes and arrhythmias.

Basic and clinical evidence suggests that omega-3 (n-3) polyunsaturated fatty acids (PUFAs) decrease fatal arrhythmias and infarct sizes. This study investigated if pericardial delivery of n-3 PUFAs would protect the myocardium from ischemic damages and arrhythmias. Acute myocardial infarctions were induced in 23 pigs with either 45 min balloon inflations or clamp occlusions of the left anterior descending coronary arteries and 180 min reperfusion. Docosahexaenoic acid (C22:6n-3, DHA, 45 mg), one of the main n-3 PUFAs in fish oil, was infused within the pericardial space only during the 40-min stabilizing phase, 45 min ischemia and initial 5 min reperfusion. Hemodynamics and cardiac functions were very similar between the DHA-treated and control groups. However, DHA therapy significantly reduced infarct sizes from 56.8 +/- 4.9% for controls (n = 12) to 28.8 +/- 7.9% (P < 0.01) for DHA-treated animals (n = 11). Compared with controls, DHA-treated animals significantly decreased heart rates and reduced ventricular arrhythmia scores during ischemia. Furthermore, three (25%) control animals experienced eight episodes of ventricular fibrillation (VF), and two died subsequent to unsuccessful defibrillation. In contrast, only 1 (9%) of 11 DHA-treated pigs elicited one episode of VF that was successfully converted via defibrillation to normal rhythm; thus, mortality was reduced from 17% in the controls to 0% in the DHA-treated animals. These data demonstrate that pericardial infusion of n-3 PUFA DHA can significantly reduce both malignant arrhythmias and infarct sizes in a porcine infarct model. Pericardial administration of n-3 PUFAs could represent a novel approach to treating or preventing myocardial infarctions.

Interatrial conduction measured during biventricular pacemaker implantation accurately predicts optimal paced atrioventricular intervals.

BACKGROUND: Optimizing atrioventricular (AV) delay during biventricular (BiV) pacemaker implantation can require substantial resources. Hence, a simpler method is desirable. We hypothesized that interatrial conduction time (IACT), measured at the time of BiV device implant, could be a surrogate value for the optimal AV delay. OBJECTIVE: This study determined the relationship between paced IACT and the optimal paced AV delay (PAV), as determined by echocardiography. METHODS: Consecutive subjects (N = 25; age = 66 +/- 10 years; M/F: 17/8) undergoing BiV pacemaker implantation and in sinus rhythm were included. Cannulation of the coronary sinus (CS) was at the operator's discretion. A quadripolar electrophysiology catheter was inserted via the guiding sheath into the inferiolateral CS to measure left atrial depolarization. The IACT was calculated as the interval between right atrial stimulation artifact and earliest deflection on the coronary sinus catheter electrogram. Subsequently, during atrial pacing the PAV was determined using transmitral pulsed wave Doppler echocardiography (iterative method). The relationship between paced IACT and PAV was then determined. RESULTS: The mean +/- SD paced IACT and PAV were 126 +/- 25 msec and 157 +/- 23 msec, respectively. There was a strong positive correlation between the paced IACT and PAV (r = 0.73, P < 0.001). The equation describing the relationship was PAV = 0.68 * (IACT + 104) msec. CONCLUSIONS: The paced IACT has a strong correlation with the echo derived optimal PAV. This method may be used to program PAV intervals without need for echocardiography in patients undergoing BiV pacemaker implantation.

Focal pharmacological modulation of atrioventricular nodal conduction via implantable catheter: a novel therapy for atrial fibrillation?

BACKGROUND: Pharmacological ventricular rate control is an acceptable atrial fibrillation (AF) therapy limited by systemic toxicity. We postulate that focal catheter-based drug delivery into the atrioventricular nodal (AVN) region may effectively control ventricular rate during AF without systemic toxicity. This study evaluated the effects of focally administered acetylcholine on AVN conduction and refractoriness during sinus rhythm and AF. METHODS AND RESULTS: Canines (n=7) were anesthetized and instrumented to assess cardiac electrophysiology and blood pressure. A custom drug delivery catheter was implanted in the AVN region. Incremental doses of acetylcholine starting at 10 microg/min were infused until complete AV block was achieved. Acetylcholine induced dose-dependent AV block. AF induction and electrophysiology measurements were performed during baseline and acetylcholine-induced first-degree and third-degree AV block. During AF, infusion of acetylcholine decreased ventricular rates from 182+/-32 to 77+/-28 and 28+/-8 bpm (first-degree and third-degree AV block, respectively; P<0.05). At the first-degree AV block dose, AVN effective refractory period increased from 186+/-37 to 282+/-33 ms, and Wenckebach cycle length increased from 271+/-29 to 378+/-58 ms (P<0.05). The first-degree AV block dose prolonged AV and AH intervals by 26% and 23% (P<0.05), whereas AA intervals and blood pressure remained unchanged, demonstrating a local effect. All effects were reversed 20 minutes after infusion was stopped. CONCLUSIONS: Focal acetylcholine delivery into the AVN increased AVN refractoriness and significantly decreased ventricular rate response during induced AF in a dose-related, reversible manner without systemic side effects. This may represent a novel therapy for AF whereby ventricular rate is controlled with the use of an implantable drug delivery system.

Decreasing pain and anxiety associated with patient-activated atrial shock: a placebo-controlled study of adjunctive sedation with oral triazolam.

INTRODUCTION: Implantable atrial defibrillators (IADs) have proved to be safe and effective in the management of atrial fibrillation. A potential limitation of self-activated IAD therapy is patient-reported pain and anxiety. The main objective of the present study was to determine whether triazolam improved patient perception of the shock experience or altered patient memory of shock discomfort relative to placebo. METHODS AND RESULTS: A total of 15 men and women (mean age: 59 +/- 6 years) were enrolled in this double-blind, placebo-controlled, crossover study of triazolam. Randomized study medication was administered orally 75 minutes prior to scheduled atrial shock delivery. Patient perception of the shock experience was assessed along with sedation, memory, anxiety, and mood. Triazolam reduced mean pre-shock anxiety (t= 2.98, df = 14, P = 0.01) and shock-related pain (t= 2.74, df = 13, P = 0.01) and intensity (t= 2.64, df = 13, P = 0.018) relative to placebo. Similarly, participants recalled less discomfort the morning after shock with triazolam than with placebo (t= 2.82, df = 11, P = 0.017). CONCLUSIONS: This study was the first to investigate the use of an oral benzodiazepine administered prior to patient-activated shock delivery with an IAD. Our data indicate that oral triazolam is beneficial in decreasing pain and anxiety associated with self-activated atrial defibrillation. If triazolam provides a similar benefit in the community to that which has been reported here, this medication could be offered to patients as an adjunct to intermittent IAD therapy.

Utility of adjunctive single oral bolus propafenone therapy in patients with atrial defibrillators.

AIMS: Previous studies have demonstrated that ambulatory atrial defibrillation shocks delivered by an implantable cardioverter-defibrillator (ICD) are safe and effective, but poorly tolerated. Separate studies have demonstrated the utility of single oral bolus propafenone for conversion of recent-onset atrial fibrillation (AF); however, most patients were hospitalized, had no structural heart disease, were taking no other antiarrhythmic drugs, and were not exposed to concomitant shock. We hypothesized that a single oral bolus dose of propafenone given early after onset would be a safe and effective adjunct to ICD-based AF therapy and improve overall therapy tolerance. METHODS AND RESULTS: A randomized three-way crossover study design was used to compare three strategies, deployed in the ambulatory setting early after AF episode onset in 35 ICD patients with advanced, drug refractory episodic/persistent syndromes, many of whom had structural heart disease and were taking other antiarrhythmic drugs: (i) single oral bolus propafenone (600 mg), followed by ICD shock if necessary; (ii) single oral bolus placebo, followed by ICD shock if necessary; and (iii) no oral bolus therapy and ICD shock if necessary (no bolus). Antiarrhythmic efficacy, defined by the restoration of sinus rhythm within 24 h, was similar during propafenone (81%) and no-bolus strategies (84%); both were significantly higher than during placebo strategy (62%). Propafenone was well tolerated and not associated with proarrhythmia. Shock use was significantly lower during propafenone strategy (19%) than during no-bolus strategy (55%); this was correlated with improved patient tolerance. CONCLUSION: Adjunctive use of single oral bolus propafenone is safe and effective in patients with an ICD and improves patient tolerance of device-based AF therapy.

Intrathecal clonidine reduces the incidence of ischemia-provoked ventricular arrhythmias in a canine postinfarction heart failure model.

BACKGROUND: Intrathecal clonidine (ITC) is used clinically to manage neuropathic pain but frequently causes hypotension and bradycardia due to centrally mediated sympatholytic effects. OBJECTIVES: The purpose of this study was to evaluate the cardiac electrophysiologic effects of thoracic ITC and its effects on ischemia-provoked ventricular arrhythmias. METHODS: Twelve mongrel dogs with healed myocardial infarctions and heart failure were evaluated. ITC was delivered locally via catheter to the T2-T4 spinal segments and was dosed to reduce heart rate (HR) by >20% to 25%. Electrophysiologic testing was performed before and after ITC. Transient (4-minute) myocardial ischemia was induced via left circumflex coronary artery occlusion on two separate occasions to provoke ventricular arrhythmias (ventricular tachycardia [VT]/ventricular fibrillation [VF]). Ischemic episodes were separated by 1 to 2 days, and dogs were randomly assigned to receive ITC or intrathecal saline flush (control) prior to the first or the second ischemic episode. RESULTS: ITC produced significant decrease in HR (31%) and increases in PR interval (22%), Wenckebach cycle length (122%), and atrial and ventricular effective refractory periods (19% and 9%, respectively) but had no significant effect on systemic blood pressure. The occurrence of VT/VF was reduced from 9 of 12 to 3 of 12 dogs when ITC was administered prior to transient myocardial ischemia (P = .04). ITC also blunted ischemia-induced HR increase by 74%. CONCLUSION: ITC reduced ischemia-induced VT/VF in a canine model of healed myocardial infarction with superimposed heart failure and acute ischemia. Results from electrophysiologic testing were consistent with a clonidine-induced reduction in cardiac sympathetic activity from the spinal cord. These data suggest that ITC administration may be a novel approach to treating ventricular arrhythmias.

Understanding atrial symptom reports: objective versus subjective predictors.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with a variety of symptoms such as dizziness, palpitations, shortness of breath, and other signs of heart failure, which in turn impact quality of life (QOL). Implantable cardioverter defibrillators with atrial therapies (ICDs-ATs) have been shown to reduce AF symptoms and improve QOL in select AF samples. METHOD: This study examined the strength of relationships between objective (device-detected AF events) versus subjective (emotional symptoms) data and AF symptoms (number) reported as part of the Patient Atrial Shock Survey of Acceptance and Tolerance Study (N = 96, 72% men, M age = 65, SD = 12). Depression and anxiety were assessed via the Center for Epidemiological Studies--Depression Scale and the-State Trait Anxiety Inventory. AF disease burden was measured via a number of device-detected AF episodes and the Atrial Tachyarrhythmia Symptom Severity Scale. RESULTS: Hierarchical multiple regression analysis indicated that negative emotions accounted for a significant 13.2% of unique variance in AF symptom score (F change (1, 54) = 9.625, P = 0.003). On the other hand, the number of device-detected AF episodes accounted for non-significant 8.2% of unique variance in the AF symptom score (P = 0.167). The full model explained 25.7% of the variance in AF symptom score (F(6, 54) = 3.110, P = 0.011). Specifically, greater number of treated AF episodes (beta= 0.251, P = 0.043) and higher levels of negative emotions (beta= 0.369, P = 0.003) predicted greater number of reported AF symptoms. CONCLUSION: Therefore, psychological distress may be a significant confounding factor affecting patient's report of AF symptoms rather than the actual experience of recurrent AF episodes.

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.

Do patients accept implantable atrial defibrillation therapy? Results from the Patient Atrial Shock Survey of Acceptance and Tolerance (PASSAT) Study.

INTRODUCTION: The Medtronic Jewel AF 7250 is an implantable cardioverter defibrillator with atrial and ventricular therapies (ICD-AT). The ICD-AT is effective in managing atrial tachyarrhythmias (atrial fibrillation [AF]), but patient acceptance remains an issue. This aim of this study was to measure ICD-AT acceptance. METHODS AND RESULTS: ICD-AT acceptance was evaluated in 96 patients enrolled in the "Jewel AF-AF-Only Study" for > or =3 months of follow-up (mean 19 months). Patients were mostly men (72%; age 65 +/- 12 years). Clinical data and a written survey (75% response rate) were used to quantify demographics, AF frequency and symptoms, atrial defibrillation therapy, quality of life (QOL), psychosocial distress, and ICD-AT therapy acceptance. From implant to survey, AF symptom and severity scores decreased by 18% (P < or = 0.05), and QOL (SF-36) scores increased by 15% to 50% (P < or = 0.05). ICD-AT therapy acceptance was high, with 71.3% of patients scoring in the 75th percentile on the Florida Patient Acceptance Survey. ICD-AT acceptance was correlated with the Physical Component Scale and Mental Health Component Scale scores of the SF-36 (r = 0.28 and 0.35, respectively). ICD-AT acceptance was negatively correlated with depressive symptomatology (r =-0.59), trait anxiety (r =-0.48), illness intrusiveness (r =-0.55), and AF symptom and severity scores (r =-0.26). ICD-AT acceptance did not correlate with preimplant cardioversions, number of atrial shocks, AF episodes detected by the device, or device implant duration. CONCLUSION: Most patients accepted ICD-AT therapy. Patients were more likely to accept ICD-AT if they had less psychosocial distress, greater QOL, and lower AF symptom burden.

Patient experiences with atrial fibrillation and treatment with implantable atrial defibrillation therapy.

BACKGROUND: Patient perspectives about their illness experiences, symptoms, and treatment are essential aspects of quality of life and provide direction for patient and provider decision making regarding innovative therapies such as implantable devices for arrhythmia. PURPOSE: The purpose of this qualitative study was to describe: 1) the experience of patients living with symptomatic, drug-refractory atrial fibrillation (AF) and 2) patient experiences and acceptance of treatment with the implantable cardioverter defibrillator (ICD) with atrial therapies (ICD-AT) including ventricular and atrial defibrillation therapy. PARTICIPANTS: Subjects were 3 women and 8 men, 35 to 80 years of age, who received the Medtronic Jewel AF 7250 ICD-AT as therapy for recurrent, drug-refractory AF, had a history of AF for 3 to 20 years and had experienced multiple treatment modalities including frequent external cardioversion in an effort to control their AF. METHODS: A semi-structured interview addressed experiences of symptoms and prior treatment for AF and experiences, concerns, and perceived benefits of the ICD-AT. Interviews were recorded and transcribed verbatim. Narratives were coded and categorized using Atlas Ti(R) software. Qualitative interpretive analysis methods were used to identify key themes. RESULTS: Before ICD-AT, patient themes focused on AF that was: 1) misdiagnosed, minimized, and poorly treated; 2) distressful because of frequent and intense AF symptoms (fatigue, dizziness, shortness of breath, and anxiety) before ICD-AT; 3) limiting of activities of daily living; 4) associated with distress from enduring previous treatment; and 5) associated with the continuous pursuit of successful treatment and maintenance of normalcy. Decision making regarding ICD-AT therapy included weighing symptom or treatment distress versus anticipated risks or benefits, hope for better outcomes, and lack of options. After ICD-AT, themes included positive perceptions of the device because of AF symptom relief, ability to resume normalcy, and medication tolerance; incorporation of shock experiences into life routines; and patient suggestions regarding preparation and social support. IMPLICATIONS: Symptoms of AF have a major negative impact on overall quality of life. Treatment with the ICD-AT confers a sense of security and reduced symptom distress. Greater provider attention to patient preparation and facilitating social support are important for future ICD-AT patient care.

Sleep quality among patients treated with implantable atrial defibrillation therapy: effect of nocturnal shock delivery and psychological distress.

INTRODUCTION: The Medtronic ICD-AT has atrial/ventricular therapies, which can be programmed to deliver atrial defibrillation during sleep, intended to potentially decrease shock anxiety/pain and lifestyle disruption. However, these shocks may diminish sleep quality. This study examined atrial shock characteristics (i.e., mode, frequency), AF symptoms, and psychological factors as determinants of sleep quality. METHODS AND RESULTS: The 96 ICD-AT patients were mostly men (72%; M age 65 +/- 12 years) and implanted for 1.6 years (SD = 0.8 years). Patients were divided into shock groups based on the proportion of mode (> or =90%) of total atrial shocks received. Patients were grouped into either automatic-nocturnal shock group (8 P.M.-8 A.M.; n = 35) or manual-awake shock group (n = 42). Psychological measures included Pittsburgh Sleep Quality Index (PSQI), Center for Epidemiology Studies-Depression Scale, State-Trait Anxiety Inventory, and Illness Intrusiveness Rating Scale. Atrial fibrillation disease burden was assessed via atrial symptom score and atrial shock use. PSQI global scores were similar between manual (7.67 +/- 2.53) and automatic shock (8.20 +/- 2.93) groups. A multiple hierarchical regression analysis indicated that no atrial shock variables were predictive of sleep quality; yet, both AF symptom (B = 0.226, P = 0.040) and depression (B = 0.392, P = 0.034) scores predicted diminished sleep quality, accounting for 42% of the variance in global sleep quality (P < 0.001). CONCLUSION: These results suggest that atrial defibrillation therapy does not have a deleterious impact on sleep. However, the significance of AF symptoms and depression indicate that comprehensive care of both physical and psychological symptomatology may improve sleep quality in ICD-AT patients.

Electrical heterogeneity and arrhythmogenesis: importance of conduction velocity dispersion.

An experimental model of conduction velocity (CV) and refractory period dispersion was established to determine which variable is a determinant of myocardial vulnerability. Anesthetized swine were instrumented with a left anterior descending coronary artery catheter for regional infusion of lidocaine (n = 6), low-dose d-sotalol (n = 4), high-dose d-sotalol (n = 6), or saline (n = 6), to create dispersion in CV (lidocaine), refractoriness (d-sotalol), or neither (saline). Ventricular fibrillation thresholds (VFTs) and refractory periods were determined at five sites (one drug perfused, four non-drug perfused). CV was determined in one drug-perfused area (left ventricular epicardial apex) and one non-drug perfused area (right ventricular epicardial base). Lidocaine and low- and high-dose d-sotalol increased VFT when stimuli were delivered in the drug-perfused area. However, lidocaine decreased VFT when stimuli were delivered at non-drug perfused areas by an average of 52%. Neither d-sotalol dose affected VFT when stimuli were delivered in non-drug perfused areas. Lidocaine increased CV dispersion by 18-26 cm/s but did not alter refractoriness. Both d-sotalol doses increased dispersion in refractoriness by 15-27 ms but did not alter CV. Saline did not affect either variable. Regional lidocaine had profibrillatory effects when stimuli were delivered in non-drug perfused areas, whereas regional d-sotalol did not. Hence, CV dispersion is a more likely determinant of myocardial vulnerability than refractoriness.

Intrapericardial therapeutics: a pharmacodynamic and pharmacokinetic comparison between pericardial and intravenous procainamide delivery.

INTRODUCTION: Procainamide delivery into the pericardial space may produce a greater and more prolonged electrophysiologic effect, particularly in thin superficial atrial tissue, compared with intravenous delivery. METHODS AND RESULTS: Swine were randomized to sequential procainamide doses delivered intravenously (n = 6) or into the pericardial space (n = 7). The cumulative pericardial doses were 0.5, 1.5, and 3.5 mg/kg, and the intravenous doses were 2, 10, and 26 mg/kg. Pericardial procainamide prolonged right atrial effective refractory period from baseline by 22% (P < 0.01) but only at the 3.5 mg/kg cumulative dose. This dose slowed interatrial conduction time by 14% (P < 0.05) and raised atrial fibrillation threshold by 70 mA (P < 0.05). Pericardial procainamide had minimal effect on ventricular electrophysiology. Similar results occurred with a single 2 mg/kg pericardial dose in a closed chest model. Intravenous 10 and 26 mg/kg cumulative doses prolonged atrial effective refractory period from baseline by 24% and 18% (P < 0.01), respectively. The 26 mg/kg cumulative intravenous dose slowed interatrial and atrial-ventricular conduction times by 27% and 17%, respectively (P < 0.05), raised atrial fibrillation threshold, and slowed ventricular conduction time by 29% (P < 0.05). Pericardial procainamide produced pericardial fluid concentrations ranging from 250 to 1,500 microg/mL, but plasma concentrations were <1 microg/mL. Intravenous procainamide doses produced pericardial fluid concentrations similar to plasma trough concentrations 0 to 12 microg/mL. CONCLUSION: The single 2 mg/kg and 3.5 mg/kg cumulative pericardial procainamide doses prolonged atrial refractoriness and raised atrial fibrillation threshold similar to the 26 mg/kg cumulative intravenous dose, but the duration of effect was similar between delivery methods. Pericardial procainamide did not affect global or endocardial ventricular electrophysiology nor was it associated with ventricular proarrhythmia.