Project description:BackgroundCardiac resynchronization therapy (CRT) is an effective treatment for patients with heart failure; however, 30% of patients do not respond to the treatment. We sought to derive patient-specific left ventricle maps of lead placement scores (LPS) that highlight target pacing lead sites for achieving a higher probability of CRT response.MethodsEighty-two subjects recruited for the ImagingCRT trial (Empiric Versus Imaging Guided Left Ventricular Lead Placement in Cardiac Resynchronization Therapy) were retrospectively analyzed. All 82 subjects had 2 contrast-enhanced full cardiac cycle 4-dimensional computed tomography scans: a baseline and a 6-month follow-up scan. CRT response was defined as a reduction in computed tomography-derived end-systolic volume ≥15%. Eight left ventricle features derived from the baseline scans were used to train a support vector machine via a bagging approach. An LPS map over the left ventricle was created for each subject as a linear combination of the support vector machine feature weights and the subject's own feature vector. Performance for distinguishing responders was performed on the original 82 subjects.ResultsFifty-two (63%) subjects were responders. Subjects with an LPS≤Q1 (lower-quartile) had a posttest probability of responding of 14% (3/21), while subjects with an LPS≥ Q3 (upper-quartile) had a posttest probability of responding of 90% (19/21). Subjects with Q1<LPS<Q3 had a posttest probability of responding that was essentially unchanged from the pretest probability (75% versus 63%, P=0.2). An LPS threshold that maximized the geometric mean of true-negative and true-positive rates identified 26/30 of the nonresponders. The area under the curve of the receiver operating characteristic curve for identifying responders with an LPS threshold was 87%.ConclusionsAn LPS map was defined using 4-dimensional computed tomography-derived features of left ventricular mechanics. The LPS correlated with CRT response, reclassifying 25% of the subjects into low probability of response, 25% into high probability of response, and 50% unchanged. These encouraging results highlight the potential utility of 4-dimensional computed tomography in guiding patient selection for CRT. The present findings need verification in larger independent data sets and prospective trials.

Project description:Objectives: To test whether (1) electromechanical dyssynchrony induces region-specific alterations in the myocardial transcriptome and (2) dyssynchrony-induced gene expression changes can be corrected by cardiac resynchronization (CRT). Background: To date, CRT is the only heart failure treatment that can both acutely and chronically increase systolic function and prolong survival, something not yet achieved by a drug therapy. However, the mechanisms underlying the benefits of CRT remain elusive. Methods: Adult dogs underwent left bundle branch ablation (LBBB) and right atrial pacing at 200 bpm for either 6 weeks (dyssynchronous heart failure, DHF, n=12) or 3 weeks followed by 3 weeks of resynchronization by bi-ventricular pacing at the same pacing rate (CRT, n=10). Control animals without LBBB were not paced (NF, n=14). Echocardiography and invasive hemodynamic measurements were performed at 3 and 6 weeks. At 6 weeks, RNA was isolated from the anterior and lateral LV walls and hybridized onto canine-specific 44K microarrays. Results: In DHF, transcriptional changes consistent with re-expression of a fetal gene program were primarily observed in the anterior LV, resulting in increased regional heterogeneity of gene expression within the left ventricle. Dyssynchrony-induced region-specific expression changes in 1050 transcripts were reversed by CRT to levels of NF hearts (false discovery rate <5%). CRT remodeled transcripts with metabolic and cell signaling function and greatly reduced regional heterogeneity of gene expression compared with DHF. Conclusions: Our results demonstrate a profound effect of electromechanical dyssynchrony on the regional cardiac transcriptome, causing gene expression changes primarily in the anterior LV wall. CRT corrected the alterations in gene expression in the anterior wall by reversing the fetal gene expression pattern, supporting a global effect of biventricular pacing on the ventricular transcriptome that extends beyond the pacing site in the lateral wall.

Project description:ObjectiveWe aimed to evaluate the diagnostic accuracy (DA) of dual-source CT coronary angiography (DSCTCA) against invasive coronary angiography (ICA) in assessing stenotic cardiac allograft vasculopathy (CAV) in heart transplant (HTX) recipients.MethodsConsecutive HTX recipients(n = 38) on annual surveillance, underwent DSCTCA prior to ICA on a 192-detector 384-slice DSCT scanner. Cases were classified as no CAV (no stenosis), any CAV (any degree of stenosis) or significant CAV (>50% stenosis).ResultsMean age was 33.66 ± 11.45 years (M:F = 27:11, median time from HTX-23.5 months). Prevalence of any CAV on DSCTCA and ICA was 44.7%(n = 17) and 39.5%(n = 15), respectively and that of significant CAV was 21.1%(n = 8) and 15.8%(n = 6), respectively. 557 (96.7%) segments were interpretable on DSCTCA. Mean radiation dose was 4.24 ± 2.15 mSv. At patient-level, the sensitivity, specificity, positive-predictive value, negative-predictive value (NPV), and DA of DSCTCA for detection of any CAV and significant CAV were 100%, 91.3%, 88.2%, 100%, 94.73% and 100%, 94%, 75%, 100%, 95% respectively. The same on segment-based analysis were 96%, 97.6%, 80%, 99.6%, 97.5% and 100%, 99.6%,86.7%,100%, 99.6%, respectively. There was excellent agreement between the two modalities for detection of any CAV and significant CAV [κ = 0.892 and 0.826 (patient-level), 0.859 and 0.927 (segment-level)]. CAC score correlated significantly with the presence of any CAV on both modalities. A diagnosis of rejection on biopsy did not correlate with any/significant CAV on DSCTCA or ICA.ConclusionHigh sensitivity and NPV of DSCTCA in the evaluation of stenotic CAV suggests that it can be an accurate and non-invasive alternative to ICA for routine surveillance of HTX recipients.Advances in knowledgeDSCTCA detects the stenotic CAV non-invasively in transplant recipients with high sensitivity, specificity and NPV when compared with catheter coronary angiography, at lower radiation doses. There is excellent agreement between CT angiography and catheter coronary angiography for detection of any CAV and significant CAV. A diagnosis of rejection on biopsy does not correlate with any/significant CAV on CT angiography or catheter angiography.

Project description:Objectives: To test whether (1) electromechanical dyssynchrony induces region-specific alterations in the myocardial transcriptome and (2) dyssynchrony-induced gene expression changes can be corrected by cardiac resynchronization (CRT). Background: To date, CRT is the only heart failure treatment that can both acutely and chronically increase systolic function and prolong survival, something not yet achieved by a drug therapy. However, the mechanisms underlying the benefits of CRT remain elusive. Methods: Adult dogs underwent left bundle branch ablation (LBBB) and right atrial pacing at 200 bpm for either 6 weeks (dyssynchronous heart failure, DHF, n=12) or 3 weeks followed by 3 weeks of resynchronization by bi-ventricular pacing at the same pacing rate (CRT, n=10). Control animals without LBBB were not paced (NF, n=14). Echocardiography and invasive hemodynamic measurements were performed at 3 and 6 weeks. At 6 weeks, RNA was isolated from the anterior and lateral LV walls and hybridized onto canine-specific 44K microarrays. Results: In DHF, transcriptional changes consistent with re-expression of a fetal gene program were primarily observed in the anterior LV, resulting in increased regional heterogeneity of gene expression within the left ventricle. Dyssynchrony-induced region-specific expression changes in 1050 transcripts were reversed by CRT to levels of NF hearts (false discovery rate <5%). CRT remodeled transcripts with metabolic and cell signaling function and greatly reduced regional heterogeneity of gene expression compared with DHF. Conclusions: Our results demonstrate a profound effect of electromechanical dyssynchrony on the regional cardiac transcriptome, causing gene expression changes primarily in the anterior LV wall. CRT corrected the alterations in gene expression in the anterior wall by reversing the fetal gene expression pattern, supporting a global effect of biventricular pacing on the ventricular transcriptome that extends beyond the pacing site in the lateral wall. Complementary study to GSE14327. While GSE14327 was designed as a 1-color microarray experiment, this series was carried out following a 2-color design (anterior and lateral LV wall labeled with Cy3 and Cy5, respectively, including dye swaps).

Dataset Information

Utility of dual-source computed tomography in cardiac resynchronization therapy-DIRECT study.

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Utility of dual-source computed tomography in cardiac resynchronization therapy-DIRECT study.

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