Dynamic Changes in High‐Sensitivity Cardiac Troponin I Are Associated with Dynamic Changes in Sum Absolute QRST Integral on Surface Electrocardiogram in Acute Decompensated Heart Failure

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135259/1/anec12379_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135259/2/anec12379.pd

Longitudinal changes in intracardiac repolarization lability in patients with implantable cardioverter-defibrillator.

PMC3740232Background: While it is known that elevated baseline intracardiac repolarization lability is associated with the risk of fast ventricular tachycardia (FVT)/ventricular fibrillation (VF), the effect of its longitudinal changes on the risk of FVT/VF is unknown. Methods and Results: Near-field (NF) right ventricular (RV) intracardiac electrograms (EGMs) were recorded every 3-6 months at rest in 248 patients with structural heart disease [mean age 61.2 ± 13.3; 185(75%) male; 162(65.3%) ischemic cardiomyopathy] and implanted cardioverter-defibrillator (ICD) or cardiac resynchronization therapy defibrillator (CRT-D) [201 (81%) primary prevention]. Intracardiac beat-to-beat QT variability index (QTVINF) was measured on NF RV EGM. During the first study phase (median 18 months), participants made on average 2.4 visits. Then remote follow-up was continued for an additional median period of 3 years. Average QTVINF did not change during the first year after ICD implantation (-0.342 ± 0.603 at baseline vs. -0.262 ± 0.552 at 6 months vs. -0.334 ± 0.603 at 12 months); however, it decreased thereafter (-0.510 ± 0.603 at 18 months; P = 0.042). Adjusted population-averaged GEE model showed that the odds of developing FVT/VF increased by 75% for each 1 unit increase in QTVINF. (OR 1.75 [95%CI 1.05-2.92]; P = 0.031). However, individual patient-specific QTVINF trends (increasing, decreasing, flat) varied from patient to patient. For a given patient, the odds of developing FVT/VF were not associated with increasing or decreasing QTVINF over time [OR 1.27; (95%CI 0.05-30.10); P = 0.881]. Conclusion: While on average the odds of FVT/VF increased with an increase in QTVINF, patient-specific longitudinal trends in QTVINF did not affect the odds of FVT/VF.JH Libraries Open Access Fun

QT interval variability in body surface ECG: measurement, physiological basis, and clinical value: position statement and consensus guidance endorsed by the European Heart Rhythm Association jointly with the ESCWorking Group on Cardiac Cellular Electrophysiology

This consensus guideline discusses the electrocardiographic phenomenon of beat-to-beat QT interval variability (QTV) on surface electrocardiograms. The text covers measurement principles, physiological basis, and clinical value of QTV. Technical considerations include QT interval measurement and the relation between QTV and heart rate variability. Research frontiers of QTV include understanding of QTV physiology, systematic evaluation of the link between QTV and direct measures of neural activity, modelling of the QTV dependence on the variability of other physiological variables, distinction between QTV and general T wave shape variability, and assessing of the QTV utility for guiding therapy. Increased QTV appears to be a risk marker of arrhythmic and cardiovascular death. It remains to be established whether it can guide therapy alone or in combination with other risk factors. QT interval variability has a possible role in non-invasive assessment of tonic sympathetic activity

ECG marker of adverse electrical remodeling post-myocardial infarction predicts outcomes in MADIT II study

PMC3522579Background Post-myocardial infarction (MI) structural remodeling is characterized by left ventricular dilatation, fibrosis, and hypertrophy of the non-infarcted myocardium. Objective The goal of our study was to quantify post-MI electrical remodeling by measuring the sum absolute QRST integral (SAI QRST). We hypothesized that adverse electrical remodeling predicts outcomes in MADIT II study participants. Methods Baseline orthogonal ECGs of 750 MADIT II study participants (448 [59.7%] ICD arm) were analyzed. SAI QRST was measured as the arithmetic sum of absolute QRST integrals over all three orthogonal ECG leads. The primary endpoint was defined as sudden cardiac death (SCD) or sustained ventricular tachycardia (VT)/ventricular fibrillation (VF) with appropriate ICD therapies. All-cause mortality served as a secondary endpoint. Results Adverse electrical remodeling in post-MI patients was characterized by wide QRS, increased magnitudes of spatial QRS and T vectors, J-point deviation, and QTc prolongation. In multivariable Cox regression analysis after adjustment for age, QRS duration, atrial fibrillation, New York Heart Association heart failure class and blood urea nitrogen, SAI QRST predicted SCD/VT/VF (HR 1.33 per 100 mV*ms (95%CI 1.11–1.59); P=0.002), and all-cause death (HR 1.27 per 100 mV*ms (95%CI 1.03–1.55), P=0.022) in both arms. No interaction with therapy arm and bundle branch block (BBB) status was found. Conclusions In MADIT II patients, increased SAI QRST is associated with increased risk of sustained VT/VF with appropriate ICD therapies and all-cause death in both ICD and in conventional medical therapy arms, and in patients with and without BBB. Further studies of SAI QRST are warranted.JH Libraries Open Access Fun

Beat‐to‐Beat Spatiotemporal Variability in the T Vector Is Associated With Sudden Cardiac Death in Participants Without Left Ventricular Hypertrophy: The Atherosclerosis Risk in Communities (ARIC) Study

Background: Despite advances in prevention and treatment of cardiovascular disease, sudden cardiac death (SCD) remains a clinical challenge. Risk stratification in the general population is needed. Methods and Results: Beat‐to‐beat spatiotemporal variability in the T vector was measured as the mean angle between consecutive T‐wave vectors (mean TT′ angle) on standard 12‐lead ECGs in 14 024 participants in the Atherosclerosis Risk in Communities (ARIC) study. Subjects with left ventricular hypertrophy, atrial arrhythmias, frequent ectopy, ventricular pacing, or QRS duration ≥120 ms were excluded. The mean spatial TT′ angle was 5.21±3.55°. During a median of 14 years of follow‐up, 235 SCDs occurred (1.24 per 1000 person‐years). After adjustment for demographics, coronary heart disease risk factors, and known ECG markers for SCD, mean TT′ angle was independently associated with SCD (hazard ratio 1.089; 95% CI 1.044 to 1.137; P90th percentile (>9.57°) was associated with a 2‐fold increase in the hazard for SCD (hazard ratio 2.01; 95% CI 1.28 to 3.16; P=0.002). In a subgroup of patients with T‐vector amplitude ≥0.2 mV, the association with SCD was almost twice as strong (hazard ratio 3.92; 95% CI 1.91 to 8.05; P<0.0001). A significant interaction between mean TT′ angle and age was found: TT′ angle was associated with SCD in participants aged <55 years (hazard ratio 1.096; 95% CI 0.043 to 1.152; P<0.0001) but not in participants aged ≥55 years (Pinteraction=0.009). Conclusions: In a large, prospective, community‐based cohort of left ventricular hypertrophy–free participants, increased beat‐to‐beat spatiotemporal variability in the T vector, as assessed by increasing TT′ angle, was associated with SCD

A framework for the definition and interpretation of the use of surrogate endpoints in interventional trials

Background: Interventional trials that evaluate treatment effects using surrogate endpoints have become increasingly common. This paper describes four linked empirical studies and the development of a framework for defining, interpreting and reporting surrogate endpoints in trials. Methods: As part of developing the CONSORT (Consolidated Standards of Reporting Trials) and SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) extensions for randomised trials reporting surrogate endpoints, we undertook a scoping review, e-Delphi study, consensus meeting, and a web survey to examine current definitions and stakeholder (including clinicians, trial investigators, patients and public partners, journal editors, and health technology experts) interpretations of surrogate endpoints as primary outcome measures in trials. Findings: Current surrogate endpoint definitional frameworks are inconsistent and unclear. Surrogate endpoints are used in trials as a substitute of the treatment effects of an intervention on the target outcome(s) of ultimate interest, events measuring how patients feel, function, or survive. Traditionally the consideration of surrogate endpoints in trials has focused on biomarkers (e.g., HDL cholesterol, blood pressure, tumour response), especially in the medical product regulatory setting. Nevertheless, the concept of surrogacy in trials is potentially broader. Intermediate outcomes that include a measure of function or symptoms (e.g., angina frequency, exercise tolerance) can also be used as substitute for target outcomes (e.g., all-cause mortality)-thereby acting as surrogate endpoints. However, we found a lack of consensus among stakeholders on accepting and interpreting intermediate outcomes in trials as surrogate endpoints or target outcomes. In our assessment, patients and health technology assessment experts appeared more likely to consider intermediate outcomes to be surrogate endpoints than clinicians and regulators. Interpretation: There is an urgent need for better understanding and reporting on the use of surrogate endpoints, especially in the setting of interventional trials. We provide a framework for the definition of surrogate endpoints (biomarkers and intermediate outcomes) and target outcomes in trials to improve future reporting and aid stakeholders' interpretation and use of trial surrogate endpoint evidence. Funding: SPIRIT-SURROGATE/CONSORT-SURROGATE project is Medical Research Council Better Research Better Health (MR/V038400/1) funded