Tolerance of High-Dose Oral Amiodarone for Cardioversion of Atrial Flutter.

In atrial arrhythmias, amiodarone is usually given either intravenously for acute management, requiring in-hospital monitoring, or orally for chronic control, as doses given 60 times per half-life, requiring weeks to reach full effect. A high-risk, 245-kg male with heart failure exacerbated by atrial flutter was successfully cardioverted using an atypically large, 8000-mg oral amiodarone dose. The only adverse effect was transient sinus arrest, which did not require intervention, only 24 hours of inpatient monitoring. Amiodarone's unique pharmacokinetics, including its long elimination half-life and its extensive distribution into a large volume of adipose tissue, make high-dose oral amiodarone boluses a reasonable strategy for cardioversion of atrial arrhythmias.

En présence d'arythmie auriculaire, l'amiodarone est généralement administrée par voie intraveineuse dans la phase aiguë de la prise en charge, ce qui nécessite une surveillance du patient en milieu hospitalier, ou encore par voie orale dans le cadre d'un traitement au long cours à des doses représentant 60 fois la demi-vie, le plein effet du médicament n'étant obtenu qu'au bout de plusieurs semaines. Un homme de 245 kg à haut risque souffrant d'insuffisance cardiaque aggravée par un flutter auriculaire a subi avec succès une cardioversion médicamenteuse faisant appel à une dose exceptionnellement élevée d'amiodarone ­ 8000 mg ­ administrée par voie orale. Le seul effet indésirable a été une pause sinusale n'ayant pas nécessité d'intervention, seulement 24 heures de surveillance en milieu hospitalier. Vu la pharmacocinétique particulière de l'amiodarone, notamment sa longue demi-vie d'élimination et sa distribution étendue dans un grand volume de tissu adipeux, l'administration perorale de ce médicament en dose de charge constitue une stratégie raisonnable de cardioversion en cas d'arythmie auriculaire.

A Novel High-Resolution Surface Electrocardiographic Method to Identify and Characterize Myocardial Scar: A Proof-of-Concept Study.

BACKGROUND: The placement of the left ventricular (LV) lead in an area free of myocardial scar is an important determinant of cardiac resynchronization therapy response. We sought to develop and validate a simple, practical, and novel electrocardiographic (ECG)-based approach to intraoperatively identify the presence of LV scar. We hypothesized that there would be a reduction in the measured amplitude of the LV pacing stimulus on the skin surface using a high-resolution (HR) ECG when pacing from LV regions with scar compared with regions without scar. We term this the ECG Amplitude Signal Evaluation (EASE) method. METHODS: Consecutive patients with ischemic LV systolic dysfunction and standard criteria for de novo cardiac resynchronization therapy implantation were prospectively enrolled. All underwent a preimplant contrast-enhanced cardiac magnetic resonance study to assess for scar. The average amplitude of the LV pacing impulse was sampled on HR surface ECG intraprocedurally and then compared with the cardiac magnetic resonance results. RESULTS: A total of 38 LV pacing sites were assessed among 13 recipients. The median voltage measured on the surface HR ECG in regions with scar was reduced by 41% (interquartile range, 17% to 63%), whereas there was no measurable change in voltage (interquartile range, 0 to 0%) in regions without scar compared with the maximal amplitude (Wilcoxon P < 0.0001). CONCLUSION: The EASE method appears to be of potential value as a novel intraoperative tool to guide LV lead placement to regions free of scar. Future work is required to validate the utility of this method in a larger patient cohort.

CONTEXTE: La mise en place de la sonde ventriculaire gauche dans une zone exempte de cicatrice myocardique est un facteur déterminant de la réponse au traitement de resynchronisation cardiaque. Nous avons cherché à développer et à valider une approche électrocardiographique (ECG) simple, concrète et novatrice afin de repérer de manière peropératoire la présence de tissu cicatriciel au ventricule gauche (VG). Nous avons émis l'hypothèse qu'il y aurait une diminution de l'amplitude du rythme de stimulation du ventricule gauche mesurée à la surface de la peau à l'ECG haute résolution (HR) lors de la stimulation de régions du VG présentant du tissu cicatriciel comparativement aux régions exemptes de cicatrices. Il s'agit de ce que nous appelons la méthode EASE ( E CG A mplitude S ignal E valuation). MÉTHODOLOGIE: Des patients vus de manière consécutive qui présentaient une dysfonction systolique ischémique du VG et répondaient aux critères standard pour l'implantation de novo d'un dispositif de resynchronisation cardiaque ont été recrutés de manière prospective. Tous ont fait l'objet d'une résonance magnétique cardiaque améliorée par injection d'un produit de contraste avant l'implantation pour évaluer la présence de tissu cicatriciel. L'amplitude moyenne de l'impulsion de stimulation du VG a été échantillonnée sur l'ECG de surface HR réalisé pendant l'intervention, puis comparée aux résultats de la résonance magnétique cardiaque. RÉSULTATS: En tout, 38 points de stimulation du VG ont été évalués chez 13 receveurs. Le voltage médian mesuré sur l'ECG de surface HR dans les régions présentant du tissu cicatriciel était réduit de 41 % (intervalle interquartile : 17 % à 63 %), tandis qu'il n'y avait pas de changement mesurable du voltage (intervalle interquartile : 0 à 0 %) dans les régions exemptes de cicatrices par rapport à l'amplitude maximale (test de Wilcoxon, p < 0,0001). CONCLUSION: La méthode EASE semble avoir une utilité potentielle en tant que nouvel outil peropératoire pour guider la mise en place de la sonde ventriculaire gauche dans les régions exemptes de cicatrices. Il faudra réaliser d'autres travaux pour valider l'utilité de cette méthode dans une cohorte de patients plus importante.

Change in Left Ventricular Ejection Fraction Following First Myocardial Infarction and Outcome.

OBJECTIVES: This study hypothesizes that a lack of left ventricular ejection fraction (LVEF) recovery after myocardial infarction (MI) would be associated with a poor outcome. BACKGROUND: A reduced LVEF early after MI identifies patients at risk of adverse outcomes. Whether the change in LVEF in the weeks to months following MI provides additional information on prognosis is less certain. METHODS: Change in LVEF between the early (2 to 7 days) and later (2 to 12 weeks) post-MI periods in patients with a first MI was assessed in 3 independent cohorts (REFINE [Risk Estimation Following Infarction Noninvasive Evaluation]; CARISMA [Cardiac Arrhythmia and Risk Stratification after Myocardial Infarction]; ISAR [Improved Stratification of Autonomy Regulation]). Patients were categorized as having no recovery (Δ ≤0%), a modest increase (Δ 1% to 9%), or a large increase (Δ ≥10%) in LVEF. The relationship between change in LVEF and risk of sudden cardiac arrest (SCA) and all-cause mortality were assessed in Cox multivariable models. RESULTS: In REFINE, patients with no LVEF recovery had a higher risk of sudden cardiac arrest (hazard ratio: 5.8; 95% confidence interval: 2.1 to 16.6; p = 0.001) and death (hazard ratio: 3.9; 95% confidence interval: 1.5 to 10.1; p < 0.001), independent of revascularization, baseline LVEF, and medical therapy compared with patients with recovery. Similar findings were observed in the other cohorts. LVEF reassessments beyond 6 weeks post-MI were more predictive of outcome than were earlier reassessments. CONCLUSIONS: The degree of LVEF recovery after a first MI provides important prognostic information. Patients with no recovery in LVEF after MI are at high risk of sudden cardiac arrest events and death.

Association of rate-controlled persistent atrial fibrillation with clinical outcome and ventricular remodelling in recipients of cardiac resynchronization therapy.

BACKGROUND: Whether patients with persistent atrial fibrillation (AF) obtain the same degree of benefit with cardiac resynchronization therapy (CRT) as those in sinus rhythm remains unclear. METHODS: We enrolled 93 patients undergoing CRT implantation, 20 (22%) of whom had rate-controlled persistent AF. The primary endpoint was CRT response defined as 1 class improvement in Specific Activity Scale and 15% reduction in left ventricular end-systolic volume (LVESV) during 12 months. Other endpoints included changes in 6-minute walk distance, quality of life, B-type natriuretic peptide, and survival. RESULTS: Baseline characteristics were similar in those with and without AF. Response to CRT was observed in 42% vs 54% of those with and without AF, respectively (P=0.3). Both groups had significant improvements in 6-minute walk distance, quality of life, and LVESV, but the improvement in LVESV was smaller in those with AF (13.7%±14.9% vs 27.7%±23.7%; P=0.02). During 2.8±1.4 years of follow-up, AF was associated with a 2.2-fold increased risk of death or transplantation (95% confidence interval, 1.2-3.9; P=0.01). CONCLUSIONS: Compared with patients without rate-controlled persistent AF, those with rate-controlled persistent AF had similar rates of clinical improvement but less left ventricular reverse remodelling in the first year after CRT. AF was associated with a markedly higher risk of death or transplantation in long-term follow-up. Given these findings, randomized studies assessing CRT efficacy in those with AF are warranted.

A multicenter, open-label study of vernakalant for the conversion of atrial fibrillation to sinus rhythm.

BACKGROUND: The efficacy and safety of vernakalant, a relatively atrial-selective antiarrhythmic agent, in converting atrial fibrillation (AF) to sinus rhythm (SR) were evaluated in this multicenter, open-label study of patients with AF lasting >3 hours and < or =45 days (RCT no. NCT00281554). METHODS: Adult patients with AF and an indication for conversion to SR received a 10-minute intravenous infusion of vernakalant (3 mg/kg). If after a 15-minute observation period AF was present, a second 10-minute infusion of intravenous vernakalant (2 mg/kg) was given. The primary efficacy end point was the proportion of patients with recent-onset AF (AF lasting >3 hours to < or =7 days) who converted to SR within 90 minutes of the start of the first infusion. Safety evaluations included vital signs, telemetry and Holter monitoring, 12-lead electrocardiography, clinical laboratory tests, physical examinations, and adverse events (AEs). RESULTS: A total of 236 hemodynamically stable patients with AF received intravenous vernakalant. Among them, 167 (71%) had recent-onset AF and were eligible for the primary efficacy end point. Vernakalant rapidly converted recent-onset AF to SR in 50.9% of patients, with a median time to conversion of 14 minutes among responders. The most common AEs were dysgeusia, sneezing, and paresthesia. These occurred at the time of vernakalant infusion, were transient, and resolved spontaneously. Ten patients (4.2%) discontinued vernakalant treatment because of AEs, most commonly (in 4 of 10) hypotension. There were no episodes of torsades de pointes, ventricular fibrillation, or sustained ventricular tachycardia. CONCLUSIONS: Vernakalant rapidly converted recent-onset AF to SR, was well tolerated, and may be a valuable therapeutic alternative for reestablishing SR in patients with recent-onset AF.

Attenuated recovery of heart rate turbulence early after myocardial infarction identifies patients at high risk for fatal or near-fatal arrhythmic events.

BACKGROUND: Autonomic dysfunction tends to improve over time after acute myocardial infarction (MI), but the clinical significance of autonomic remodeling is not well known. OBJECTIVE: The purpose of this study was to test the hypothesis that the amount of recovery of autonomic function early after MI is associated with a risk for serious arrhythmias. METHODS: The prognostic significance of autonomic remodeling after MI was assessed in one post-MI cohort [Cardiac Arrhythmia and Risk Stratification after Myocardial Infarction (CARISMA)] and validated in a second cohort [Risk Estimation After Infarction, Noninvasive Evaluation (REFINE)]. Changes in heart rate variability (DeltaHRV) and heart rate turbulence (DeltaHRT) were measured from 24-hour ECG recordings performed early (5-21 days) and later (6 weeks) after MI in CARISMA (n = 312). DeltaHRV and DeltaHRT were similarly measured from early (2-4 weeks) and later (10-14 weeks) post-MI recordings in REFINE (n = 322). RESULTS: HRV and HRT increased over time in both cohorts. Attenuated recovery of autonomic function, defined as DeltaHRT slope <2.0 ms/RR, was associated with a 9.4-fold (95% confidence interval 1.2-71.6; P = .03) higher risk of ECG-documented sustained ventricular tachycardia or ventricular fibrillation in CARISMA and a 7.0-fold (95% confidence interval 1.6-29.6; P = .009) higher risk of fatal or near-fatal events in REFINE. Changes in HRV and HRT were not predictive of nonarrhythmic death in either cohort. CONCLUSION: Attenuated recovery of autonomic function early after MI consistently predicts a higher risk of fatal or near-fatal arrhythmic events. A lack of improvement in HRT early after MI appears to be a specific marker for serious arrhythmic events.

Post-exercise assessment of cardiac repolarization alternans in patients with coronary artery disease using the modified moving average method.

OBJECTIVES: We sought to evaluate the utility of T-wave alternans (TWA) assessment in the immediate post-exercise period to identify and validate cutpoints for the modified moving average (MMA) assessment method. BACKGROUND: The presence of TWA is associated with an increased risk of cardiovascular death (CVD). The immediate post-exercise period, where increased physiologic stress and minimal surface artifact coexist, appears ideal to implement the MMA method. METHODS: A test (n = 322) and validation cohort (n = 681) provided 1,003 patients with coronary artery disease (CAD). We assessed TWA immediately after exercise. The outcomes, CVD and mortality, were adjudicated independent of the TWA results. RESULTS: During 48 months of follow-up 85 deaths, 54 categorized as CVD (64%), were observed. A linear relationship between the magnitude of TWA and the risk of CVD was identified. As a continuous measure TWA voltage was equivalent to ejection fraction in predicting the risk of CVD. To facilitate clinical application, a sensitive, modest predictive accuracy (20 microV) and a specific, greater predictive accuracy MMA cutpoint (60 microV) were identified and validated. Each cutpoint was associated with a 2.5-fold greater risk of CVD, independent of other important variables, including ejection fraction. CONCLUSIONS: Post-exercise assessment of TWA using the MMA method is a strong, independent predictor of risk in patients with CAD. The 20-microV cutpoint (87% sensitivity) appears to be most suitable in higher-risk patients, whereas the 60-microV cutpoint (95% specificity) appears more appropriate when TWA is used as a single screening test in those at lower risk. (Assessment of Noninvasive Methods to Identify Patients at Risk of Serious Arrhythmias After a Heart Attack; NCT00399503).

Predictive value of repeated versus single N-terminal pro B-type natriuretic peptide measurements early after-myocardial infarction.

BACKGROUND: A single, markedly elevated B-type natriuretic peptide (BNP) serum concentration predicts an increased risk of death after myocardial infarction (MI), though its sensitivity and predictive accuracy are low. We compared the predictive value of a modestly and persistently elevated, versus a single, markedly elevated measurement of N terminal pro-BNP (NT-BNP) early after MI. METHODS AND RESULTS: NT-BNP was measured 2-4, 6-10, and 14-18 weeks after MI. The median age of the 100 patients was 61 years, median left ventricular ejection fraction (LVEF) was 0.40, and 88% were males. Over a median follow-up of 39 months, 10 patients died. The initial median NT-BNP was 802 pg/mL and declined over time (P = 0.002). An initial NT-BNP > or =2,300 pg/mL (upper quintile) was observed in 19 patients and predicted a 3.4-fold higher independent risk of death (P = 0.05), with modest sensitivity (30%) and positive predictive accuracy (16%). A NT-BNP consistently > or =1,200 pg/mL (upper tertile) was observed in 19 patients, and was associated with a 5.7-fold higher independent risk of death (P = 0.01), with a higher sensitivity (50%) and positive predictive accuracy (26%) than a single, markedly elevated NT-BNP measurement. CONCLUSIONS: A moderately and persistently elevated NT-BNP in the early post-MI period was associated with a 5.7-fold higher risk of death, independent of age, LVEF, and functional class. Compared with a single measurement, serial NT-BNP measurements early after MI were more accurate predictors of risk of death.

Beneficial effects of statin therapy for prevention of atrial fibrillation following DDDR pacemaker implantation.

AIMS: Data suggest that atrial pacing, statins, angiotensin-converting enzyme-inhibitors and angiotensin receptor blocking drugs prevent atrial tachycardia/atrial fibrillation (AT/AF) in some patients. The clinical predictors of at/af recurrence following dual-chamber pacemaker insertion were examined in 185 consecutive patients with paroxysmal AF. METHODS AND RESULTS: Predictors of AT/AF recurrence were evaluated in this observational cohort study. The time to first AT/AF recurrence and AT/AF burden (h/day) was retrieved at each follow-up visit by interrogating the pacemaker. AT/AF recurred following pacemaker implantation in 157 (85%) patients. At 1 year of follow-up, patients without recurrence were more likely to be on statin therapy (54%) when compared with patients without statin therapy (25%, chi = 12.31, P = 0.0004). Statin therapy was the only significant predictor of AT/AF recurrence in a multivariate logistic regression model (adjusted odds ratio 0.33, 95% confidence interval 0.14-0.74, P = 0.007). AT/AF burden was significantly lower in the group on statin therapy (median 0.10 h/day) when compared with the group not on statin therapy (median 0.39 h/day, P = 0.0059). CONCLUSION: AT/AF recurs frequently following pacemaker implantation in patients with sinus node disease. The progression to permanent AF remains low over time. Statin therapy was significantly associated with AT/AF suppression.

Pacemakers, implantable cardioverter/defibrillators, and extracorporeal shockwave lithotripsy: evidence-based guidelines for the modern era.

Early work examining interactions between extracorporeal shockwave lithotripsy (SWL) and implantable pacemakers or implantable cardioverter/defibrillators suggested that shockwave oversensing may result in inappropriate suppression of pacing, delivery of antitachycardia pacing therapy, delivery of inappropriate shock therapy, or outright damage to such devices. In the absence of national guidelines, those provided by manufacturers are nonuniform and practice patterns vary between centers. Improvements in SWL energy delivery as well as in device shielding and discrimination technologies have demonstrated improved safety data in recent years. We review these advances in both technologies as well as the most recent data to construct practice guidelines for the modern era.

Transmural temporospatial left ventricular activation during pacing from different sites: potential implications for optimal pacing.

AIMS: Previous studies showed that right ventricular (RV) endocardial pacing can be deleterious even in individuals with initially normal left ventricular (LV) function. The mechanism(s) by which RV endocardial pacing may cause LV dysfunction is unknown. This study compares the temporospatial LV transmyocardial activation profiles during sinus rhythm with normal His/Purkinje conduction vs. currently utilized and proposed cardiac pacing sites. METHODS AND RESULTS: Mongrel dogs were instrumented with transmural electrodes that tracked transmyocardial activation sequences at five sites in the LV. Pacing/recording catheters were positioned in the RV apex and on the RV and LV sides of the ventricular septum. An epicardial pacing electrode was also sewn to the mid-lateral LV epicardium. Electrograms were recorded during sinus rhythm and pacing from the RV endocardium, LV septum, LV epicardium and during biventricular pacing. Compared to normal sinus/His/Purkinje rhythm (NSR), RV endocardial pacing significantly (P < 0.05) prolonged transmural activation (NSR endocardium 6.1 +/- 1 ms vs. RV endocardium 23.0 +/- 2.6 ms). The highly ordered temporospatial pattern of transmural activation during sinus rhythm was replaced with dispersion and intermingling of endo-, mid-, and epicardial activation. LV epicardial and biventricular pacing did not correct these abnormalities. Only LV septal pacing achieved the transmural and transseptal activation sequences similar to sinus rhythm. CONCLUSION: Clinically utilized pacing modalities, including biventricular pacing, cause abnormal transmyocardial activation. LV septal pacing results in transmyocardial activation patterns that closely resemble those seen in sinus rhythm.

Noninvasive risk assessment early after a myocardial infarction the REFINE study.

OBJECTIVES: This study sought to determine whether combined assessment of autonomic tone plus cardiac electrical substrate identifies most patients at risk of serious events after myocardial infarction (MI) and to compare assessment at 2 to 4 weeks versus 10 to 14 weeks after MI. BACKGROUND: Methods to identify most patients at risk of serious events after MI are required. METHODS: Patients (n = 322) with an ejection fraction (EF) <0.50 in the initial week after MI were followed up for a median of 47 months. Serial assessment of autonomic tone, including heart rate turbulence (HRT), electrical substrate, including T-wave alternans (TWA), and EF was performed, interpreted blinded, and categorized using pre-specified cut-points where available. The primary outcome was cardiac death or resuscitated cardiac arrest. All-cause mortality and fatal or nonfatal cardiac arrest were secondary outcomes. RESULTS: Mean EF significantly increased over the initial 8 weeks after MI. Testing 2 to 4 weeks after MI did not reliably identify patients at risk, whereas testing at 10 to 14 weeks did. The 20% of patients with impaired HRT, abnormal exercise TWA, and an EF <0.50 beyond 8 weeks post-MI had a 5.2 (95% confidence interval [CI] 2.4 to 11.3, p < 0.001) higher adjusted risk of the primary outcome. This combination identified 52% of those at risk, with good positive (23%; 95% CI 17% to 26%) and negative (95%; 95% CI 93% to 97%) accuracy. Similar results were observed for the secondary outcomes. CONCLUSIONS: Impaired HRT, abnormal TWA, and an EF <0.50 beyond 8 weeks after MI reliably identify patients at risk of serious events. (Assessment of Noninvasive Methods to Identify Patients at Risk of Serious Arrhythmias After a Heart Attack; http://www.clinicaltrials.gov/ct/show/NCT00399503?order=1; NCT00399503).

Pulmonary edema post-cardioversion: a potential calcium signalling problem.

The present report describes an unusual case of pulmonary edema after adenosine cardioversion of a supraventricular tachycardia. Despite a structurally normal heart, a 52-year-old woman presented with pulmonary edema on two separate occasions, having had her atrioventricular nodal re-entrant tachycardia terminated with 12 mg of intravenous adenosine. A third similar episode of tachycardia that was terminated with verapamil was not complicated by pulmonary edema.

Cardiac video analysis using Hodge-Helmholtz field decomposition.

The critical points (also known as phase singularities) in the heart reflect the pathological change of the heart tissue, and hence can be used to describe and analyze the dynamics of the cardiac electrical activity. As a result, the detection of these critical points can lead to correct understanding and effective therapy of the tachycardia. In this paper, we propose a novel approach to address this problem. The proposed approach includes four stages: image smoothing, motion estimation, motion decomposition, and detection of the critical points. In the image smoothing stage, the noisy cardiac optical data are smoothed using anisotropic diffusion equation. The conduction velocity fields of the cardiac electrical patterns can then be estimated from two consecutive smoothed images. Using the recently developed discrete Hodge-Helmholtz motion decomposition technique, the curl-free and divergence-free potential surfaces of an estimated velocity field are extracted. Finally, hierarchically searching the minima and maxima on the potential surfaces, the sources, sinks, and rotational centers are located with high accuracy. Experimental results with four real cardiac videos show that the proposed approach performs satisfactorily, especially for the cardiac electrical patterns with simple propagations.

Heart block in mice overexpressing calcineurin but not NF-AT3.

OBJECTIVE: Overexpression of calcineurin causes cardiac hypertrophy and arrhythmic deaths. During disease development, sinus bradycardia followed by high degree atrioventricular (AV) block finally culminating in ventricular asystole has been observed over time in calcineurin hearts. AV block is associated with the development of pleomorphic ventricular tachycardia in mice and downregulation of potassium currents in ventricular myocytes. We tested the hypothesis that the abnormalities of AV block and propensity to ventricular tachycardia relate to overexpression of calcineurin independent of the development of hypertrophy. METHODS: Cardiac electrophysiologic properties were compared in isolated perfused hearts with ventricular hypertrophy due to overexpression of calcineurin or NF-AT3 and in their corresponding wild types at 15 or 30 days of age. RESULTS: Compared to wild-type hearts, significant prolongation of sinus node recovery times was noted in both NF-AT3 and calcineurin hearts. Compared to wild-type hearts, Wenckebach cycle length (WCL) and the left ventricular effective refractory period (LVERP) were significantly prolonged in the calcineurin hearts (p<0.05) but not NF-AT3 hearts. In calcineurin mice, left ventricular effective refractory period impinged on Wenckebach cycle length resulting in a significant correlation between left ventricular effective refractory period and Wenckebach cycle length (r(2)=0.56). No such correlation was observed for wild type or NF-AT3 hearts. At 30 days of development, ventricular tachycardia developed in 70% of calcineurin hearts compared to 0% wild-type hearts (p=0.003), whereas ventricular tachycardia was observed in 33% of NF-AT3 hearts and 10% of corresponding wild-type hearts (p=NS). CONCLUSIONS: The prolonged ventricular refractoriness, seen only in calcineurin hearts, impinges on Wenckebach cycle length resulting in heart block and is associated with propensity to ventricular tachycardia.

In vivo temporal and spatial distribution of depolarization and repolarization and the illusive murine T wave.

This study assessed in vivo temporal and spatial electrophysiological properties of murine hearts and the effect of manipulation of transmural action potential durations (APDs) on T wave morphology. Monophasic action potentials (MAPs) were acquired from multiple left ventricular sites. All MAPs exhibited a plateau phase, with a spike and dome appearance being present in epicardial recordings. Activation occurred from endocardial apex to epicardial apex and apex to base while repolarization occurred from base (shortest 90 eta0 level of repolarization (MAP90), 95.4 +/- 8.9 ms) to apex and epicardium to endocardium (longest MAP90, 110.77 +/- 10.6 ms). The peak of phase 0 of the epicardial base MAP correlated with the return to baseline of the initial and usually dominant waveform of the QRS and the onset of the second usually smaller wave, which clearly occurred in early repolarization, thus establishing where depolarization ended and repolarization began on the murine ECG. This second waveform was similar to the J wave seen in larger animals. Despite temporal and spatial electrophysiological similarities, a T wave is frequently not seen on a murine ECG. There are several determinants of T wave morphology, including transmural activation time, slope of phase 3 repolarization and differences in epicardial, endocardial and M cell APDs. Experimental manipulation of murine transmural gradients by shortening epicardial MAP(90) to 84% of endocardial MAP90 the epicardial/endocardial ratio in larger mammals when a positive T wave is present, resulted in a positive murine T wave. Thus, manipulation of the transmural gradients such that they are similar to larger mammals can result in T waves with similar morphology.

Autoimmune cardiomyopathy and heart block develop spontaneously in HLA-DQ8 transgenic IAbeta knockout NOD mice.

A line of nonobese diabetic (NOD) mice expressing the human diabetes-associated HLA-DQ8 transgene in the absence of mouse IAbeta failed to show spontaneous insulitis or diabetes, but rather developed dilated cardiomyopathy, leading to early death from heart failure. Pathology in these animals results from an organ- and cell-specific autoimmune response against normal cardiomyoctes in the atrial and ventricular walls, as well as against very similar myocytes present in the outermost muscle layer surrounding the pulmonary veins. Progression of the autoimmune process could be followed by serial ECG measurements; irradiation of young animals significantly delayed disease progression, and this effect could be reversed by adoptive transfer of splenocytes taken from older animals with complete heart block. Disease progression could also be blocked by cyclosporin A treatment, but was accelerated by injection of complete Fruend's adjuvant. The constellation of findings of spontaneously arising destructive focal lymphocytic infiltrates within the myocardium, rising titers of circulating anticardiac autoantibodies, dilation of the cardiac chambers, and gradual progression to end-stage heart failure bears a striking resemblance to what is seen in humans with idiopathic dilated cardiomyopathy, a serious and often life-threatening medical condition. This transgenic strain provides a highly relevant animal model for human autoimmune myocarditis and postinflammatory dilated cardiomyopathy.

Multitasking and the technical quality of the electrocardiogram.

BACKGROUND: The electrocardiogram (ECG) is a powerful clinical tool for diagnosing cardiac abnormalities. Proper ECG data acquisition is essential because it allows physicians to interpret ECG results accurately and efficiently. This is especially important for patients with acute myocardial infarction, so that they can receive early treatment. As a result of multitasking, ECGs are acquired by two groups of personnel at the University of Alberta Hospital, Edmonton - ECG technologists and non-ECG technologists. OBJECTIVE: To evaluate the effectiveness and quality of ECG acquisition at the University of Alberta Hospital site. METHODS: All adult ECGs acquired at the University of Alberta Hospital site from January 1 to June 30, 2000 were assessed. An ECG was classified as unacceptable if it lacked demographics identifying the patient, and/or it was of such poor technical quality that the interpretation was compromised. RESULTS: Of 25,509 ECGs acquired during this period, 13,849 (54%) and 11,660 (46%) ECGs were acquired by ECG technologists and non-ECG technologists, respectively. Eleven ECGs (0.08%) acquired by the ECG technologists and 3683 ECGs (32%) acquired by the non-ECG technologists were of unacceptable quality. The technical cost spent on these unacceptable ECGs is approximately $100,000 a year at this institution. CONCLUSIONS: Multitasking has resulted in a high rate of unacceptable ECGs. There is a significant difference in the effectiveness and quality of ECG acquisition performed by ECG technologists and non-ECG technologists. Poorly acquired ECGs impede proper diagnosis for patients, subject the institution to potential medical legal consequences and add an unnecessary burden to the health care budget.