Cluster analysis of extracellular matrix biomarkers predicts the development of impaired systolic function within 1 year of acute myocardial infarction.

The clinical utility of combining extracellular matrix (ECM) biomarkers to predict the development of impaired systolic function following acute myocardial infarction (AMI) remains largely undetermined. A combination of ELISA and multiplexing assays were performed to measure matrix metalloproteinase (MMP)-2, MMP-3, MMP-8, MMP-9, periostin, N-terminal type I procollagen (PINP) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in plasma samples from 120 AMI patients. All patients had an echocardiogram within 1 year of AMI, and were divided into impaired (n = 37, LVEF < 50%) and preserved (n = 83, LVEF ≥ 50%) systolic function groups. Exploratory factor analysis was performed on log-transformed biomarkers using principle axis analysis with Oblimin rotation. Cluster analysis was performed on log-transformed and normalised biomarkers using Ward's method of minimum variance and the squared Euclidean distance metric. Upon univariate analysis, current smoking, prescription of ACE inhibitors at discharge, peak hsTnT > 610 ng/L (median), MMP-8 levels, Factor 1 scores and Cluster One assignment were predictive of impaired systolic function. Upon multivariate analysis, Cluster One assignment (odds ratio [95% CI], 2.74 [1.04-7.23], p = 0.04) remained an independent predictor of systolic dysfunction in combination with clinical variables. These observations support the usefulness of combining ECM biomarkers using cluster analysis for predicting the development of impaired systolic function in AMI patients.

An IL-6-IL-8 score derived from principal component analysis is predictive of adverse outcome in acute myocardial infarction.

INTRODUCTION: Many studies have shown that elevated biomarkers of inflammation following acute myocardial infarction (AMI) are associated with major adverse cardiovascular events (MACE). However, the optimal way of measuring the complex inflammatory response following AMI has not been determined. In this study we explore the use of principal component analysis (PCA) utilising multiple inflammatory cytokines to generate a combined cytokine score that may be predictive of MACE post-AMI. METHODS: Thirteen inflammatory cytokines were measured in plasma of 317 AMI patients, drawn 48-72 h following symptom onset. Patients were followed-up for one year to determine the incidence of MACE. PCA was used to generate a combined score using six cytokines that were detectable in the majority of patients (IL-1ß, -6, -8, and -10; MCP-1; and RANTES), and using a subset of cytokines that were associated with MACE on univariate analysis. Multivariate models using baseline characteristics, elevated individual cytokines and PCA-derived scores determined independent predictors of MACE. RESULTS: IL-6 and IL-8 were significantly associated with MACE on univariate analysis and were combined using PCA into an IL-6-IL-8 score. The combined cytokine score and IL-6-IL-8 PCA-derived score were both significantly associated with MACE on univariate analysis. In multivariate models IL-6-IL-8 scores (OR = 2.77, p = 0.007) and IL-6 levels (OR = 2.18, p = 0.035) were found to be independent predictors of MACE. CONCLUSION: An IL-6-IL-8 score derived from PCA was found to independently predict MACE at one year and was a stronger predictor than any individual cytokine, which suggests this may be an appropriate strategy to quantify inflammation post-AMI. Further investigation is required to determine the optimal set of cytokines to measure in this context.

Long-term single-center comparison of ICD lead survival: Evidence for premature Linox lead failure.

INTRODUCTION: ICD lead failure is a potential source of significant morbidity and mortality. This study investigates the survival rates of Sprint Quattro, Endotak Reliance, and Linox ICD leads. METHODS AND RESULTS: A retrospective cohort study of all patients with an ICD implanted between January 2007 and December 2012 from the Wellington Hospital region, New Zealand, a tertiary referral center. Lead and patient details were established by review of clinical notes and the PaceArt Optima database. We analyzed a total of 287 implants using Sprint Quattro (n  =  92), Endotak Reliance (n  =  37), Linox (n  =  151), Riata (n  =  4), and Sprint Fidelis (n  =  2) leads. Median follow-up was 61.6 (26.0-81.6) months for Sprint Quattro leads, 66.7 (53.3-88.8) months for Linox leads, and 82.9 (45.9-107.4) months for Endotak Reliance leads. There were 20 cases of lead failure of which 19 were in Linox leads. The 4-, 6-, and 8-year survival for Linox leads was 97% (92.6-99.1), 93% (85.5-96.5), and 76% (62.3-85.5), respectively. The predominant abnormality was detection of nonphysiological electrical signals. Linox lead failure was associated with a younger age of patient (49.2 vs. 57.7 years, P  =  0.007). CONCLUSIONS: The 7-year survival of Linox leads was significantly worse than shown in Biotronik surveillance reports, but in line with other single-center studies from around the world.

Analysis of ECG Measures of Cardiac Repolarization in Relation to Arrhythmic Events in an Implantable Cardioverter Defibrillator Population.

BACKGROUND: ECG-derived measures of cardiac repolarization may have utility in risk prediction of future ventricular arrhythmia, and a range of different measures have been proposed. We compared time-based, vectorcardiographic, and singular value decomposition (SVD) derived measures of repolarization to determine which was most predictive of appropriate therapy in an ICD population. METHODS: We examined the independent prognostic value of a range of repolarization measures derived from 60 second 12-lead ECG recordings in 150 patients receiving new ICD implants in relation to the occurrence of appropriate therapy during follow-up. RESULTS: Over an average follow-up of 2.15 ± 0.87 years, male gender, presence of premature ventricular complex (PVC), relative T wave residuum (TWR-rel, measures regional repolarization heterogeneity), and TCRT (the total cosine R-to-T, describes the global angle between repolarization and depolarization wavefronts) were the only independent predictors of appropriate therapy. With every 0.01% increase in TWR-rel, there was 2% increased risk of appropriate therapy (HR = 1.02, 95% CI 1.006-1.034, P < 0.001). With every 1° decrease in TCRT, there was an increase in arrhythmic risk of 0.9% (HR 1.009, 95% CI 1.003-1.015, P = 0.003). CONCLUSIONS: The use of advanced analytic ECG techniques to derive measures of repolarization abnormality might shave utility in risk stratification in an ICD population.

Cardiac troponin levels following implantable cardioverter defibrillation implantation and testing.

AIMS: Previous studies have reported the defibrillation testing during implantable cardioverter defibrillator (ICD) implantation is associated with elevated cardiac biomarkers and ST-segment electrocardiogram (ECG) changes suggesting that shocks during testing may cause harm. However, the effects of testing have not been isolated from the implant procedure itself, where lead deployment may cause myocardial damage. This prospective study examined high sensitivity troponin T (hs-TnT) levels and ECG changes during ICD implanting alone, ICD implantation with testing and device testing as a stand-alone procedure. METHODS AND RESULTS: We examined hs-TnT at baseline, and 6-8 h post procedure and 12 lead ECG at baseline, and 30 s, 5 min, and 10 min post right ventricle lead deployment and post defibrillation. There was no significant change in hs-TnT levels in a group of patients (n = 11) undergoing defibrillation testing alone, while hs-TnT was significantly elevated in patients undergoing implantation alone (n = 13, median increase 96%, P = 0.005) and in patients undergoing implantation and testing (n = 13, median increase 161%, P = 0.005). There was a significant correlation between the number of lead deployments and the percentage change in hs-TnT (r = -0.51, P = 0.01), but no correlation between either the number of shocks (r = 0.26, P = 0.25) or the total delivered energy (r = 0.24, P = 0.30) and percentage change in hs-TnT. CONCLUSION: Implantation of ICD leads was associated with release of troponin, but we did not observe any evidence that ICD shocks alone cause myocardial injury.

Correlation between vectorcardiographic measures and cardiac magnetic resonance imaging of the left ventricle in an implantable cardioverter defibrillator population.

BACKGROUND: Measures of vectorcardiographic changes and LV remodelling have been associated with arrhythmic risk. However the correlation between the two modalities is not well characterised. METHODS: We correlated spatial QRS-T angle and ventricular gradient with cardiac MRI derived LV global measures and scar pattern in 66 ICD recipients. RESULTS: Spatial QRS-T angle was significantly larger in patients with ischaemic scar than those without scar (150°±22° vs. 119°±46°, p=0.01). Larger spatial QRS-T angle was also correlated with more depressed LV function, more dilated LV and larger LV mass. Ventricular gradient azimuth was significantly different between patients with no scar, non-ischaemic scar and ischaemic scar (20°±49° vs. 38°±62° vs. 65°±48°, p=0.009), but independent of spatial QRS-T angle and LV structure. CONCLUSIONS: Spatial QRS-T angle and ventricular gradient are partially related to LV structural properties. Further investigation is warranted to examine their comparative and combined prognostic value in risk stratification of ventricular arrhythmias.

Standard 12-lead electrocardiography measures predictive of increased appropriate therapy in implantable cardioverter defibrillator recipients.

AIMS: Identification of patients most likely to benefit from implantable cardioverter defibrillator (ICD) implant remains a complex challenge. This study aimed to investigate the utility of measures derived from standard 10 s 12-lead electrocardiogrphy (ECG) without complex signal processing in predicting appropriate therapy in an ICD population. METHODS AND RESULTS: We examined 108 ICD patients for primary (n = 32) and secondary prevention (n = 76). Baseline clinical data and characteristics of QRS complex, T-wave, and heart rate from standard 12-lead ECG were examined and related to the occurrence of subsequent appropriate therapy. Over a mean follow-up of 29 ± 11 months, 44% of patients received appropriate therapy. Patients with depressed heart rate variability (HRV) (≤6.5%) were 2.68 [95% confidence interval (CI) 1.21-5.90, P = 0.015] times more likely to receive appropriate therapy than patients with HRV >6.5%. In patients with bundle branch block (BBB), large QRS dispersion of >39 ms was associated with 2.88 times risk (95% CI 1.24-6.71, P = 0.014) of experiencing appropriate therapy than those with QRS dispersion <39 ms. In patients without BBB, reduced maximum T-wave amplitude (<0.4 mV) were 3.82 times (95% CI 1.63-8.93, P = 0.002) more likely to receive appropriate therapy compared with those with maximum T-wave amplitude >0.4 mV. History of atrial arrhythmia [hazard ratio (HR) = 2.30, 95% CI 1.29-4.12, P = 0.005] and secondary prevention (HR = 2.55, 95% CI 1.14-5.71, P = 0.022) were also predictive of device therapy. CONCLUSION: Measurements from standard 12-lead ECG were predictive of appropriate therapy in a heterogeneous ICD population. Incorporation of 12-lead ECG parameters such as these into risk stratification models may improve our ability to select patients for ICD implantation.

An unmet need for implantable cardioverter-defibrillators in New Zealand.

AIMS: This study examined the prior history of all patients presenting to the regional ambulance service with community cardiac arrest to determine what proportion of these patients had prior indications for implanted cardioverter-defibrillator (ICD) therapy. METHODS AND RESULTS: We reviewed the medical history of all adult patients presenting to our regional ambulance service with cardiac arrest between 1 June 2007 and 31 May 2008 (n= 144). Patients were classified as either not having an ICD indication, having a possible ICD indication, or having an ICD indication by two electrophysiologists. Eighty-seven patients (60%) had no pre-existing indication for an ICD. Twenty-two patients (15%) had a possible indication for an ICD but required further investigation to confirm this. This group consisted of 6 patients (4%) with previously documented left ventricular ejection fraction <35%, but without a measurement in the last 12 months, 14 patients (10%) with heart failure (n= 10) or syncope (n= 4) without appropriate investigations, and 2 patients with an ICD indication but with co-morbidities that required further investigation. Thirty-five patients (24%) had a documented indication for an ICD. In 11 (8%) there was no evidence of a contraindication, in 3 (2%) alternative therapy was judged more appropriate, and in 21 (15%) contraindications to ICD implantation were also present. Addition of the 11 patients with an ICD indication and the 6 patients with a documented indication requiring updated measurement, 17 patients (12%) had a prior documented ICD indication but had not been referred for this therapy. CONCLUSIONS: Our observation that 12% of sudden cardiac arrest patients had prior indications for an ICD demonstrates that there is an unmet need for ICDs in New Zealand.