Barbara Szepietowska

Insulin resistance predicts the risk for recurrent coronary events in post-infarction patients

BACKGROUND We investigated the risk for recurrent coronary events associated with insulin resistance in post-infarction patients from the Thrombogenic Factors and Recurrent Coronary Events (THROMBO) study. METHODS The association between insulin resistance expressed by Homeostatic Model As-sessment 2 for Insulin Resistance (HOMA2-IR) and the risk for recurrent coronary events was investigated in a cohort of 1,032 patients evaluated 2 months after myocardial infarction (MI) with a follow-up of 26 months. The endpoint for the study was recurrent coronary event defined as cardiac death, nonfatal MI, or unstable angina, whichever occurred first. We used time dependent survival analysis and Cox proportional hazards regression method to determine the association between HOMA2 categorized as high > 75th percentile and endpoints after adjustment for relevant clinical covariates and series of thrombogenic and dyslipogenic factors. RESULTS High HOMA2-IR defined as in fourth quartile (≥ 2.4) was associated with increased risk for recurrent coronary events (HR 1.44; CI 1.03-2.01; p = 0.03) after adjustment for the clinical covariates: age, gender, diabetes, prior MI, pulmonary congestion, coronary artery bypass grafting and percutaneous transluminal coronary angioplasty. The highest risk of cardiac events was observed in non-obese patients (body mass index [BMI] ≤ 30 kg/m2) with high HOMA2-IR (HR 1.5; CI 1.02-2.22; p = 0.038). The plasma level of plasminogen activa-tor inhibitor-1 was associated with higher risk for recurrent coronary events in patients with insulin resistance (HR 1.79; CI 1.05-3.03; p = 0.03, interaction p = 0.018). CONCLUSIONS In conclusion, insulin resistance predicts recurrence of coronary events in post-infarction population. HOMA2-IR is better than BMI in stratifying risk of recurrent coronary events.

Pharmacologic Conversion during Dofetilide Treatment for Persistent Atrial Fibrillation: CONVERSION DURING DOFETILIDE INITIATION

Dofetilide is a pure IKr blocker and is one of the few drugs specifically studied and approved in the United States for the management of persistent atrial fibrillation (AF). Dofetilide has been noted to have a high rate of pharmacologic conversion during initial dosing in prior smaller studies. The intent of the study was to examine the safety of an inpatient loading strategy, and the incidence and patterns of pharmacologic conversion by dofetilide during the treatment of persistent AF in a large consecutive cohort.

Validation of an automatic diagnosis of strict left bundle branch block criteria using 12‐lead electrocardiograms

Strict left bundle branch block (LBBB) criteria were recently proposed to identify LBBB patients to benefit most from cardiac resynchronization therapy (CRT). The aim of our study was to automate identification of strict LBBB in order to facilitate its broader application.

Metabolic syndrome is associated with different clinical outcome after cardiac resynchronization therapy in patients with ischemic and non-ischemic cardiomyopathy

BACKGROUND Although association of metabolic syndrome (MS) and ischemic heart disease is strongly established, it is not known whether presence of MS may differently influence clinical responses to cardiac resynchronization therapy (CRT). The aim of this study was to evaluate the associations between obesity and metabolic features and the clinical outcome after cardiac resynchronization with defibrillator therapy (CRT-D), compared to an implantable cardioverter defibrillator (ICD). METHODS The risk of heart failure (HF) or death and death alone was evaluated in 829 non-obese patients, 156 obese patients without MS, and 277 obese patients with MS (all with left bundle branch block), who were enrolled in the Multicenter Automatic Defibrillator Implanta-tion Trial with Cardiac Resynchronization Therapy (MADIT-CRT). RESULTS Obese patients with MS (HR 0.50, 95% CI 0.32-0.77, p = 0.002), obese patients without MS (HR 0.57, 95% CI 0.30-1.06, p = 0.077), and non-obese patients (HR 0.48, 95% CI 0.37-0.62, p < 0.001) had a similar risk reduction of HF/death in response to CRT-D therapy when compared to ICD patients. However, among those with non-ischemic cardiomyo-pathy, obese patients with MS experienced a 90% reduction for HF/death (HR 0.11, 95% CI 0.04-0.32, p < 0.001), whereas obese patients without MS had no reduction (HR 0.98, 95% CI 0.48-1.98, p = 0.951; interaction p < 0.001). The reverse was observed in ischemic car-diomyopathy patients: obese patients with MS had no reduction in the risk of HF/death (HR 0.80, 95% CI 0.48-1.34, p = 0.402), while obese patients without MS showed a significant reduction in the risk of events (HR 0.15, 95% CI 0.04-0.65, p = 0.011; interaction p = 0.036). Similar trends were observed for the endpoint of death. CONCLUSIONS Presence of MS differentiates the response to CRT in obese patients with is-chemic and non-ischemic etiology for HF.

Ablation of very late recurrence after initially successful ablation of atrial fibrillation

The concept of pulmonary vein isolation (PVI) for the catheter treatment of atrial fibrillation (AF) revolutionized the ablation field and has been performed in many tens of thousands of patients. It is now recognized as the foundational procedure for paroxysmal AF [1–3] but also the only proven effective intervention for patients with persistent AF [4]. The burgeoning popularity of the procedure is a testament to the substantial medium term clinical success, particularly relative to drug therapy. However, as patients have been systematically followed, it has become apparent that a significant minority would experience “very late recurrences (VLR),” even years after successful procedures [5–8]. After 10 years, about 30% of patients have AF recurrence but the incidence increases to 70% in the highest risk subgroup comprised patients with hypertension and pre-ablation persistent AF [9]. Patients with VLR may choose to undergo a very late reablation. The factors that drive AF to reappear after years of quiescence are unknown, however, observations from these late repeat ablation procedures may provide some insight. This report describes the largest published series of very late re-ablation procedures, including procedural observations and subsequent clinical response, derived from a cohort that was prospectively enrolled and systematically followed for many years. Patients were included if part of a series of 445 patients who were identified and enrolled after 1 year of freedom from AF after their index PVI (previously reported in references 3 and 4); and if presenting with ≥ 2 symptomatic VLR AF events. At redo ablation procedures, re-PVI was uniformly performed if needed; additional strategies were also pursued at discretion of operator based on clinical presentation and procedural findings. No systematic criteria were applied to the decision-making process of ablation strategy. Ultimately, 106 patients (age 63.3 ± 11.8 years; original indication, paroxysmal AF in 57.1% and persistent AF in 42.9%) underwent VLR re-ablation 4.7 ± 2.3 years after index PVI. At the VLR procedure, permanent complete PVI was found in only 3 (2.8%) patients and in the remaining 103 patients, 2.7 ± 1.6 reconnected PVs were re-isolated. The distribution of reconnections was as follows: 1 PV (15%), 2 PVs (28%), 3 PVs (19%) and 4 PVs (38%). Additional left atrial substrate ablation included: linear lesions (n = 14), targeting complex fractionated atrial electrograms (n = 1), focal impulse and rotor modulation (n = 7) and thoracoscopic isolation of posterior wall (n = 9) [10]. After VLR ablation, all patients were followed off antiarrhythmic drugs for 22.0 ± 19.2 months; seven were lost to follow-up. Periodic ambulatory ECG monitoring was performed in all patients. Overall, after a 3-month blanking period, 46 (46.5%) returned to drug-free freedom from AF (including 31 who had only re-PVI) (Fig. 1), and an additional 7 (7%) became AF-free on previously ineffective drug. Of the 46 (46.5%) with recurrent AF, 22 (22.2%) evolved to refractory persistent AF. Among the demographic and clinical characteristics, there were no differences between patients who did and did not have AF-freedom. Among procedure characteristics, there was no difference in outcome based on PV pattern of reconnection, or if patients underwent simple redo PVI vs PVI combined with any type of substrate ablation (p = 0.4); however, the specific addition of thoracoscopic posterior left atrial wall isolation predicted greater freedom from AF (p = 0.01). The small number of patients who underwent thoracoscopic ablation precluded statistical comparisons. An increasing volume of patients is returning for reablation despite years of AF freedom after their initial PVI. * Jonathan S. Steinberg jsteinberg@smgnj.com

Clinical and echocardiographic parameters as risk factors for atrial fibrillation in patients with hypertrophic cardiomyopathy

Atrial fibrillation (AF) is a common complication in patients with hypertrophic cardiomyopathy (HCM) and may contribute to high cardiovascular morbidity and mortality. Therefore, it is important to assess parameters associated with AF in HCM patients.

Response to the letter regarding article “Metabolic syndrome is associated with different clinical outcome after cardiac resynchronization therapy in patients with ischemic and non-ischemic cardiomyopathy”

We would like to thank the Authors for the commentary to our paper [1]. The commentary furthermore highlighted the importance of fuel metabolism in failing heart and significance of the intervention strategies, which may directly or indirectly target major metabolic pathways balancing glucose and free fatty acids metabolism. It should be noted that in Multicenter Automatic Deffibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) population, only 15 subjects were treated with trimetazidine, not allowing further evaluation. Our report demonstrated that patients with metabolic syndrome (MS) depending on etiology for heart failure (HF) presented with different response to cardiac resynchronization therapy (CRT). MS patients derive significant benefit from CRT if present with non-ischemic cardiomyopathy, whereas obese patients without MS show no significant reduction in events. This study suggests that the risk for HF and death may be modulated by presence of MS, a clinical surrogate for insulin resistance [1]. The current hypothesis is that CRT, among other effects, for example on cardiac remodeling, may also improve fuel metabolism of the failing heart. It is possible that improvement in fuel metabolism may correspond to better clinical response to CRT and reduction in risk for HF and death. In animal studies, CRT treatment was attributed to activation of important metabolic and insulin signal transduction protein kinase B pathway (PKB) known as Akt [2]. It is generally accepted that falling heart switches its fuel metabolism from long chain fatty acids to glucose [3] but in people with MS with insulin resistance as predominant pathological factor, glucose is less available for utilization. Therefore, activation of defective PKB/AKt by CRT may potentially modulate glucose uptake in the failing heart. Although it is only speculative, this study also suggests that intrinsic properties of myocardium fuel metabolism affected by MS may play a role in response to CRT. Future studies are needed to investigate mechanism of CRT in relation to myocardium fuel metabolism and cellular responses in falling heart.

Automatic Diagnosis of Strict Left Bundle Branch Block from Standard 12-lead Electrocardiogram

Strict Left Bundle Branch Block (LBBB) criteria were recently proposed to identify patients with complete LBBB to benefit most from Cardiac Resynchronization Therapy (CRT). The objective of our study was to automate this strict LBBB criteria in order to facilitate broader application of the criteria which require the measurements of subtle QRS patterns from standard 12-lead ECGs. We developed a series of algorithms to automatically detect and measure the QRS parameters required for strict LBBB criteria. A total of 612 signal-averaged 12-lead ECGs from 612 LBBB patients were used to train and validate the algorithms. Four clinicians independently performed adjudication on equally assigned ECGs to assess the performance of automatic results comparing to manually adjudicated results, as well as the inter-observer and intra-observer variabilities. Overall 95% and 86% of sensitivity and specificity are reached for detecting complete LBBB. Our study shows good performance in reference to manual results.