Electrocardiographic localization of the site of origin of ventricular tachycardia in patients with prior myocardial infarction

AbstractThe utility of the 12 lead electrocardiogram (ECG) in identifying the site of origin of sustained ventricular tachycardia in patients with previous myocardial infarction was studied. A new mapping grid, based on biplanar fluoroscopic imaging of the heart, was utilized for the definition of left ventricular endocardial sites. On the basis of QRS configurations resulting from left ventricular endocardial pacing at disparate sites in 22 patients (Group I), ECG features that were specific for particular sites were identified and used to construct an algorithm. Apical and basal sites were differentiated by the QRS configuration in leads V4 and aVR, anterior and inferior sites by that in leads III III and V6 and septal and lateral sites were differentiated using leads I, aVL and V1.The algorithm was used to predict the site of earliest endocardial activation during 44 episodes of sustained ventricular tachycardia in a second group of 42 patients (Group II) in a blinded fashion. Anterior sites were correctly predicted in 83% of cases, inferior sites in 84%, septal sites in 90% and lateral sites in 82% of cases. Apical and basal sites were each correctly predicted in 70% of cases, whereas intermediate sites were less well predicted (29 to 55%) on the basis of QRS configuration. Precise localization of the site of origin of ventricular tachycardia (in all three planes) was achieved in 17 cases (39%), and in 16 cases (36%) the site of origin was immediately adjacent to the predicted site.Prediction of the site of origin of ventricular tachycardia from the 12 lead ECG may serve as a useful, time-saving adjunct to, but not a substitute for, activation sequence mapping during ventricular tachycardia

Immediate reproducibility of electrically induced sustained monomorphic ventricular tachycardia before and during antiarrhythmic therapy

AbstractThe immediate reproducibility of sustained ventricular tachycardia induction was evaluated prospectively during 106 studies performed in 53 patients with clinical sustained monomorphic ventricular tachycardia. Programmed electrical stimulation was performed twice, using the same protocol during 53 drug-free studies and 53 subsequent studies on antiarrhythmic therapy.Sustained monomorphic ventricular tachycardia was reproduced in 104 (98%) of the 106 studies. There was no significant difference in the incidence of reproducible tachycardia in the drug-free state compared with that observed during treatment with different classes of antiarrhythmic drugs. An increase in the number of extrastimuli was required to reinitiate the tachycardia in 9 (11%) of 83 studies in which single or double extrastimuli were initially required to induce the tachycardia. In 39 (37%) of 104 studies with reproducible tachycardia induction, the two tachycardias significantly differed in electrocardiographic (ECG) configuration and cycle length.These observations suggest that the overall reproducibility of ventricular tachycardia induction is sufficiently high to provide a reliable marker for evaluating the efficacy of therapeutic interventions. However, specific tachycardia characteristics such as cycle length and ECG configuration are more variable even within the same study and may be less useful in assessing the effects of subsequent interventions

Determinants of the outcome of electrophysiologic study in patients with ventricular tachyarrhythmias

To determine those factors predictive of the ability to both initiate and suppress ventricular tachyarrhythmias during electrophysiologic study, the results of programmed cardiac stimulation were evaluated in 261 patients: 66 presenting with nonsustained ventricular tachycardia, 91 with sustained ventricular tachycardia and 104 with ventricular fibrillation. Multivariate logistic regression analysis revealed that the presenting arrhythmia was a potent and independent predictor of the ability to provoke ventricular arrhythmias at electrophysiologic study; a history of myocardial infarction and male sex were also significant independent predictors. Of patients presenting with sustained ventricular tachycardia, 89% (81 of 91) had inducible ventricular arrhythmias compared with 61 (40 of 66) and 66% (69 of 104) of patients with nonsustained ventricular tachycardia and ventricular fibrillation, respectively.Complete suppression of inducible arrhythmias could be achieved in only 52% (34 of 66) of patients with sustained ventricular tachycardia, compared with 73 (24 of 33) and 75% (46 of 61) of patients presenting with nonsustained ventricular tachycardia and ventricular fibrillation, respectively. Multivariate analysis showed that the major independent determinants of the ability to suppress inducible arrhythmias were the number of drug trials performed before electrophysiologic study (inversely correlated) and the nature of the induced arrhythmia.The nature of the presenting clinical arrhythmia is, therefore, a highly significant and independent predictor of the ability to induce ventricular arrhythmias during electrophysiologic testing and an important determinant of the ability to suppress induced arrhythmias in patients with spontaneous ventricular tachyarrhythmias

Purines and the Anti-Epileptic Actions of Ketogenic Diets

Ketogenic diets are high in fat and low in carbohydrates and represent a well-established and effective treatmentalternative to anti-epileptic drugs. Ketogenic diets are used for the management of a variety of difficult-to-treat or intractableseizure disorders, especially pediatric refractory epilepsy. However, it has been shown that this dietary therapycan reduce seizures in people of all ages, and ketogenic diets are being applied to other prevalent medical conditions suchas diabetes. Although used effectively to treat epilepsy for nearly 90 years, the mechanism(s) by which ketogenic dietswork to reduce seizures remain ill-understood. One mechanism receiving increased attention is based on findings that ketogenicdiets increase the brain energy molecule ATP, and may also increase the levels and actions of the related endogenousinhibitory neuromodulator adenosine. ATP and adenosine have both been identified as important modulators of seizures;seizures increase the actions of these purines, these purines regulate epileptic activity in brain, adenosine receptorantagonists are pro-convulsant, and adenosinergic mechanisms have been implicated previously in the actions of approvedanti-epileptic therapeutics. Here we will review recent literature and describe findings that shed light on mechanistic relationshipsbetween ketogenic diets and the purines ATP and adenosine. These emerging mechanisms hold great promisefor the effective therapeutic management of epileptic seizures and other neurological conditions

Factors Influencing Appropriate Firing of the Implanted Defibrillator for Ventricular Tachycardia/Fibrillation Findings From the Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II)

ObjectivesThe purpose of this study was to prospectively examine the role of clinical, laboratory, echocardiographic, and electrophysiological variables as predictors of appropriate initial implantable cardioverter-defibrillator (ICD) therapy for ventricular tachycardia (VT) or ventricular fibrillation (VF) or death in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II) population.BackgroundThere is limited information regarding the determinants of appropriate ICD therapy in patients with reduced ventricular function after a myocardial infarction.MethodsWe used secondary analysis in one arm of a multicenter randomized clinical trial in patients with a previous myocardial infarction and reduced left ventricular function.ResultsWe analyzed baseline and follow-up data on 719 patients enrolled in the ICD arm of the MADIT-II study. Appropriate ICD therapy was observed in 169 subjects. Clinical, laboratory, echocardiographic, and electrophysiological variables, along with measures of clinical instability such as interim hospitalization for congestive heart failure (IH-CHF) and interim hospitalization for coronary events (IH-CE), were examined with proportional hazards models and Kaplan-Meier time-to-event curves before and after first interim hospitalization. Interim hospitalization-CHF, IH-CE, no beta-blockers, digitalis use, blood urea nitrogen (BUN) >25, body mass index (BMI) ≥30 kg/m2, and New York Heart Association functional class >II were associated with increased risk for appropriate ICD therapy for VT, VF, or death. In a multivariate (stepwise selection) analysis, IH-CHF was associated with an increased risk for the end point of either VT or VF (hazard ratio [HR] 2.52, 95% confidence interval [CI] 1.69 to 3.74, p < 0.001) and for the combined end point of VT, VF, or death (HR 2.97, 95% CI 2.15 to 4.09, p < 0.001). Interim hospitalization-CE was associated with an increased risk for VT, VF, or death (HR 1.66, 95% CI 1.09 to 2.52, p = 0.02).ConclusionsThese results provide important mechanistic information, suggesting that worsening clinical condition and cardiac instability, as reflected by an IH-CHF or IH-CE, are subsequently associated with a significant increase in the risk for appropriate ICD therapy (for VT/VF) and death

Gelatin Methacryloyl Bioadhesive Improves Survival and Reduces Scar Burden in a Mouse Model of Myocardial Infarction.

Background Delivery of hydrogels to the heart is a promising strategy for mitigating the detrimental impact of myocardial infarction (MI). Challenges associated with the in vivo delivery of currently available hydrogels have limited clinical translation of this technology. Gelatin methacryloyl (GelMA) bioadhesive hydrogel could address many of the limitations of available hydrogels. The goal of this proof-of-concept study was to evaluate the cardioprotective potential of GelMA in a mouse model of MI. Methods and Results The physical properties of GelMA bioadhesive hydrogel were optimized in vitro. Impact of GelMA bioadhesive hydrogel on post-MI recovery was then assessed in vivo. In 20 mice, GelMA bioadhesive hydrogel was applied to the epicardial surface of the heart at the time of experimental MI. An additional 20 mice underwent MI but received no GelMA bioadhesive hydrogel. Survival rates were compared for GelMA-treated and untreated mice. Left ventricular function was assessed 3&nbsp;weeks after experimental MI with transthoracic echocardiography. Left ventricular scar burden was measured with postmortem morphometric analysis. Survival rates at 3&nbsp;weeks post-MI were 89% for GelMA-treated mice and 50% for untreated mice (P=0.011). Left ventricular contractile function was better in GelMA-treated than untreated mice (fractional shortening 37% versus 26%, P&lt;0.001). Average scar burden in GelMA-treated mice was lower than in untreated mice (6% versus 22%, P=0.017). Conclusions Epicardial GelMA bioadhesive application at the time of experimental MI was performed safely and was associated with significantly improved post-MI survival compared with control animals. In addition, GelMA treatment was associated with significantly better preservation of left ventricular function and reduced scar burden