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Background: Dual-source computed tomography (CT) can evaluate left ventricular (LV) dyssynchrony, myocardial scar, and coronary venous anatomy in patients undergoing cardiac resynchronization therapy (CRT)., Objective: We aimed to determine whether dual-source CT predicts clinical CRT outcomes and reduces intraprocedural time., Methods: In this prospective study, 54 patients scheduled for CRT (mean age 63 ± 11 years; 74% men) underwent preprocedural CT to assess their venous anatomy as well as CT-derived dyssynchrony metrics and myocardial scar. Based on 1:1 randomization, the implanting physician had preimplant knowledge of the venous anatomy in half the patients. In blinded analyses, we measured time to maximal wall thickness and inward wall motion to determine (1) CT global and segmental dyssynchrony and (2) concordance of lead location to regional LV mechanical contraction. End points were 6-month CRT response measured using heart failure clinical composite score and 2-year major adverse cardiac events (MACE)., Results: There were 72% CRT responders and 17% with MACE. Two wall motion dyssynchrony indices-global wall motion and opposing anteroseptal-inferolateral wall motion-predicted MACE (P < .01). Lead location concordant to regions of maximal wall thickness was associated with less MACE (P < .01). No CT dyssynchrony metrics predicted 6-month CRT response (P = NS for all). Myocardial scar (43%), posterolateral wall scar (28%), and total scar burden did not predict outcomes (P = NS for all). Preknowledge of coronary venous anatomy by CT did not reduce implant or fluoroscopy time (P = NS for both)., Conclusion: Two CT dyssynchrony metrics predicted 2-year MACE, and LV lead location concordant to regions of maximal wall thickness was associated with less MACE. Other CT factors had little utility in CRT., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Cardiac hypertrophy increases the risk of developing heart failure and cardiovascular death. The neutrophil inflammatory protein, lipocalin-2 (LCN2/NGAL), is elevated in certain forms of cardiac hypertrophy and acute heart failure. However, a specific role for LCN2 in predisposition and etiology of hypertrophy and the relevant genetic determinants are unclear. Here, we defined the role of LCN2 in concentric cardiac hypertrophy in terms of pathophysiology, inflammatory expression networks, and genomic determinants., Methods and Results: We used 3 experimental models: a polygenic model of cardiac hypertrophy and heart failure, a model of intrauterine growth restriction and Lcn2 -knockout mouse; cultured cardiomyocytes; and 2 human cohorts: 114 type 2 diabetes mellitus patients and 2064 healthy subjects of the YFS (Young Finns Study). In hypertrophic heart rats, cardiac and circulating Lcn2 was significantly overexpressed before, during, and after development of cardiac hypertrophy and heart failure. Lcn2 expression was increased in hypertrophic hearts in a model of intrauterine growth restriction, whereas Lcn2 -knockout mice had smaller hearts. In cultured cardiomyocytes, Lcn2 activated molecular hypertrophic pathways and increased cell size, but reduced proliferation and cell numbers. Increased LCN2 was associated with cardiac hypertrophy and diastolic dysfunction in diabetes mellitus. In the YFS, LCN2 expression was associated with body mass index and cardiac mass and with levels of inflammatory markers. The single-nucleotide polymorphism, rs13297295, located near LCN2 defined a significant cis -eQTL for LCN2 expression., Conclusions: Direct effects of LCN2 on cardiomyocyte size and number and the consistent associations in experimental and human analyses reveal a central role for LCN2 in the ontogeny of cardiac hypertrophy and heart failure., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Despite the benefit of CRT in select patients with heart failure (HF), there remains significant need for predicting those at risk for adverse outcomes for this effective but costly therapy. CysC, an emerging marker of renal function, is predictive of worsening symptoms and mortality in patients with HF. This study assessed the utility of baseline and serial measures of cystatin C (CysC), compared to conventional creatinine-based measures of renal function (estimated glomerular filtration rate, eGFR), in predicting clinical outcomes following cardiac resynchronization therapy (CRT)., Methods: In 133 patients, we measured peripheral venous (PV) and coronary sinus (CS) CysC concentrations and peripheral creatinine levels at the time of CRT implant. Study endpoints included clinical response to CRT at 6 months and major adverse cardiac events (MACE) at 2 years., Results: While all 3 renal metrics were predictive of MACE (all adjusted p ≤ 0.02), only CysC was associated with CRT non-response at 6 months (adjusted odds ratio 3.6, p = 0.02). CysC improved prediction of CRT non-response (p ≤ 0.003) in net reclassification index analysis compared to models utilizing standard renal metrics. Serial CysC > 1mg/L was associated with 6-month CRT non-response and reduced 6-minute walk distance as well as 2-year MACE (all p ≤ 0.04)., Conclusion: In patients undergoing CRT, CysC demonstrated incremental benefit in the prediction of CRT non-response when compared to standard metrics of renal function. Baseline and serial measures of elevated CysC were predictive of CRT non-response and functional status at 6 months as well as long-term clinical outcomes., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: A significant minority of patients receiving cardiac resynchronization therapy (CRT) remain nonresponsive to this intervention., Objective: This study aimed to determine whether coronary sinus (CS) or baseline peripheral venous (PV) levels of established and emerging heart failure (HF) biomarkers are predictive of CRT outcomes., Methods: In 73 patients (aged 68 ± 12 years; 83% men; ejection fraction 27% ± 7%) with CS and PV blood samples drawn simultaneously at the time of CRT device implantation, we measured amino-terminal pro-B-type natriuretic peptide (NT-proBNP), galectin-3 (gal-3), and soluble ST2 (sST2) levels. NT-proBNP concentrations >2000 pg/mL, gal-3 concentrations >25.9 ng/mL, and sST2 concentrations >35 ng/mL were considered positive on the basis of established PV cut points for identifying "high-risk" individuals with HF. CRT response was adjudicated by the HF Clinical Composite Score. A major adverse cardiovascular event (MACE) was defined as the composite end point of death, cardiac transplant, left ventricular assist device, and HF hospitalization at 2 years., Results: NT-proBNP concentrations were 20% higher in the CS than in the periphery, while gal-3 and sST2 concentrations were 10% higher in the periphery than in the CS (all P < .001). There were 45% CRT nonresponders at 6 months and 16 (22%) patients with MACE. Triple-positive CS values yielded the highest specificity of 95% for predicting CRT nonresponse. Consistently, CS strategies identified patients at higher risk of developing MACE, with >11-fold adjusted increase for triple-positive CS patients compared to triple-negative patients (all P ≤ .04). PV strategies were not predictive of MACE., Conclusion: Our findings suggest that CS sampling of HF biomarkers may be better than PV sampling for predicting CRT outcomes. Larger studies are needed to confirm our findings., (Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Various electrophysiological procedures and device implantation has been shown to improve morbidity and mortality in patients with atrial fibrillation (AF) and patients with heart failure (HF). Noninvasive cardiac imaging is used extensively in the preprocedural patient selection and for procedural guidance. In this review, we will discuss the application of preprocedural cardiac imaging in patients with AF prior to pulmonary vein and left atrial ablation as well as insertion of left atrial occluder device. We also discuss the role of noninvasive cardiac imaging in the selection of appropriate HF patients for device therapy as well as their use in guiding implantation of biventricular pacemaker for cardiac resynchronization therapy by assessing left ventricular ejection fraction, coronary venous anatomy, mechanical dyssynchrony and myocardial scar. We describe new research associated with preprocedural imaging in these patient cohorts.

Aims: Cardiac resynchronization therapy is showing benefits for an increasing number of indications but fails to predict response in up to 20-30% of subjects. Echocardiographically assessed dyssynchrony has been proposed as a potential stratifier but current methods are time-consuming and suffer poor reproducibility, thus limiting their clinical utility. This study compared the accuracy, time efficiency, and reproducibility of automated tissue synchronization imaging (Auto TSI) vs. established manual tissue velocity imaging (TVI) techniques for the assessment of intra-ventricular dyssynchrony in sinus and non-sinus rhythm., Methods and Results: Fifty consecutive stable systolic heart failure patients on optimal guideline-based medical therapy underwent intra-ventricular dyssynchrony assessment [time to peak velocity (Ts), septal to lateral delay (SLD), and dyssynchrony index (DI)] with TVI and Auto TSI techniques, enabling the assessment of agreement, time efficiency, and reproducibility. Statistical analyses included Pearson's correlation, Bland-Altman's statistics, and coefficient of reproducibility. There was excellent agreement between Auto TSI and TVI for the measurement of Ts [r=0.92, P<0.001, limits of agreement (LOA): -27.3 to 56.5 ms], SLD (r=0.94, P<0.001, LOA: -41 to 49 ms), and DI (r=0.89, P<0.001, LOA: -12.2 to 12.6 ms) which persisted irrespective of cardiac rhythm [Ts: sinus (n=32) r=0.93, P<0.001; non-sinus (n=18) r=0.91, P<0.001]. Automated TSI was more time efficient (3±1 vs. 14±2 min, P<0.001) and demonstrated superior reproducibility: intra-observer (5.5 vs. 9.6%) and inter-observer variability (9.5 vs. 13.4%)., Conclusion: Automated TSI enables rapid, reproducible intra-ventricular dyssynchrony assessment and overcomes some of the limitations of conventional techniques in sinus and non-sinus rhythm.