Project description:BackgroundWhether reprogramming of cardiac resynchronization therapy (CRT) to increase electrical synchrony translates into echocardiographic improvement remains unclear. SyncAV is an algorithm that allows fusion of intrinsic conduction with biventricular pacing. We aimed to assess whether reprogramming chronically implanted CRT devices with SyncAV is associated with improved echocardiographic parameters.MethodsPatients at a quaternary center with previously implanted CRT devices with a programmable SyncAV algorithm underwent routine electrocardiography-based SyncAV optimization during regular device clinic visits. This analysis included only patients who could be programmed to the SyncAV algorithm (i.e., in sinus rhythm with intrinsic atrioventricular conduction). Echocardiography was performed before and 6 months after CRT optimization.ResultsOf 64 consecutive, potentially eligible patients who underwent assessment, 34 who were able to undergo SyncAV programming were included. Their mean age was 74 ± 9 years, 41% were female, and 59% had ischemic cardiomyopathy. The mean time from CRT implant to SyncAV optimization was 17.8 ± 8.5 months. At 6-month follow-up, SyncAV optimization was associated with a significant increase in left ventricular ejection fraction (LVEF) (mean LVEF 36.5% ± 13.3% vs 30.9% ± 13.3%; P < 0.001) and a reduction in left ventricular end-systolic volume (LVESV) (mean LVESV 110.5 ± 57.5 mL vs 89.6 ± 52.4 mL; P < 0.001) compared with baseline existing CRT programming.ConclusionCRT reprogramming to maximize biventricular fusion pacing significantly increased LVEF and reduced LVESV in patients with chronic CRT devices. Further studies are needed to assess if a continuous fusion pacing algorithm improves long-term clinical outcomes and to identify which patients are most likely to derive benefit.
Project description:BackgroundWhether reprogramming of cardiac resynchronization therapy (CRT) to increase electrical synchrony translates into echocardiographic improvement remains unclear. SyncAV is an algorithm that allows fusion of intrinsic conduction with biventricular pacing. We aimed to assess whether reprogramming chronically implanted CRT devices with SyncAV is associated with improved echocardiographic parameters.MethodsPatients at a quaternary center with previously implanted CRT devices with a programmable SyncAV algorithm underwent routine electrocardiography-based SyncAV optimization during regular device clinic visits. This analysis included only patients who could be programmed to the SyncAV algorithm (i.e., in sinus rhythm with intrinsic atrioventricular conduction). Echocardiography was performed before and 6 months after CRT optimization.ResultsOf 64 consecutive, potentially eligible patients who underwent assessment, 34 who were able to undergo SyncAV programming were included. Their mean age was 74 ± 9 years, 41% were female, and 59% had ischemic cardiomyopathy. The mean time from CRT implant to SyncAV optimization was 17.8 ± 8.5 months. At 6-month follow-up, SyncAV optimization was associated with a significant increase in left ventricular ejection fraction (LVEF) (mean LVEF 36.5% ± 13.3% vs 30.9% ± 13.3%; P < 0.001) and a reduction in left ventricular end-systolic volume (LVESV) (mean LVESV 110.5 ± 57.5 mL vs 89.6 ± 52.4 mL; P < 0.001) compared with baseline existing CRT programming.ConclusionCRT reprogramming to maximize biventricular fusion pacing significantly increased LVEF and reduced LVESV in patients with chronic CRT devices. Further studies are needed to assess if a continuous fusion pacing algorithm improves long-term clinical outcomes and to identify which patients are most likely to derive benefit.
Project description:BackgroundWhether reprogramming of cardiac resynchronization therapy (CRT) to increase electrical synchrony translates into echocardiographic improvement remains unclear. SyncAV is an algorithm that allows fusion of intrinsic conduction with biventricular pacing. We aimed to assess whether reprogramming chronically implanted CRT devices with SyncAV is associated with improved echocardiographic parameters.MethodsPatients at a quaternary center with previously implanted CRT devices with a programmable SyncAV algorithm underwent routine electrocardiography-based SyncAV optimization during regular device clinic visits. This analysis included only patients who could be programmed to the SyncAV algorithm (i.e., in sinus rhythm with intrinsic atrioventricular conduction). Echocardiography was performed before and 6 months after CRT optimization.ResultsOf 64 consecutive, potentially eligible patients who underwent assessment, 34 who were able to undergo SyncAV programming were included. Their mean age was 74 ± 9 years, 41% were female, and 59% had ischemic cardiomyopathy. The mean time from CRT implant to SyncAV optimization was 17.8 ± 8.5 months. At 6-month follow-up, SyncAV optimization was associated with a significant increase in left ventricular ejection fraction (LVEF) (mean LVEF 36.5% ± 13.3% vs 30.9% ± 13.3%; P < 0.001) and a reduction in left ventricular end-systolic volume (LVESV) (mean LVESV 110.5 ± 57.5 mL vs 89.6 ± 52.4 mL; P < 0.001) compared with baseline existing CRT programming.ConclusionCRT reprogramming to maximize biventricular fusion pacing significantly increased LVEF and reduced LVESV in patients with chronic CRT devices. Further studies are needed to assess if a continuous fusion pacing algorithm improves long-term clinical outcomes and to identify which patients are most likely to derive benefit.
Project description:Systolic heart failure is a major problem for Americans today, with 550,000 new cases diagnosed per year, and ultimately contributes to 287,000 deaths annually. While pharmacologic therapy has drastically improved outcomes in patients with systolic heart failure, hospitalizations from systolic heart failure continue to increase and remain a major cost burden. In response to this unmet need, recent years have seen dramatic improvements in device-based therapy targeting one cause of systolic dysfunction: dyssynchronous ventricular contraction. Cardiac resynchronization therapy aims to restore mechanical synchrony by electrically activating the heart in a synchronized manner. This review summarizes the rationale for cardiac resynchronization therapy, evidence for its use, current guidelines, and ongoing and future directions for research.
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: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: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).
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. Designed as a 1-color experiments, samples from anterior and lateral left ventricular myocardium from non-failing, DHF and CRT animals were labeled with Cy3 and hybridized onto Agilent 44K long oligonucleotide arrays.
Project description:BackgroundRoutine atrioventricular optimization (AVO) has not been shown to improve outcomes with cardiac resynchronization therapy (CRT). However, more recently subgroup analyses of multicenter CRT trials have identified electrocardiographic or lead positions associated with benefit from AVO. Therefore, the purpose of this analysis was to evaluate whether interventricular electrical delay modifies the impact of AVO on reverse remodeling with CRT.MethodsThis substudy of the SMART-AV trial (SMARTDELAY Determined AV Optimization) included 275 subjects who were randomized to either an electrogram-based AVO (SmartDelay) or nominal atrioventricular delay (120 ms). Interventricular delay was defined as the time between the peaks of the right ventricular (RV) and left ventricular (LV) electrograms (RV-LV duration). CRT response was defined prospectively as a >15% reduction in LV end-systolic volume from implant to 6 months.ResultsThe cohort was 68% men, with a mean age of 65±11 years and LV ejection fraction of 28±8%. Longer RV-LV durations were significantly associated with CRT response ( P<0.01) for the entire cohort. Moreover, the benefit of AVO increased as RV-LV duration prolonged. At the longest quartile, there was a 4.26× greater odds of a remodeling response compared with nominal atrioventricular delays ( P=0.010).ConclusionsBaseline interventricular delay predicted CRT response. At long RV-LV durations, AVO can increase the likelihood of reverse remodeling with CRT. AVO and LV lead location optimized to maximize interventricular delay may work synergistically to increase CRT response.Clinical trial registrationURL: https://www.clinicaltrials.gov . Unique identifier: NCT00874445.
Project description:Cardiac resynchronization therapy (CRT) device implantation is associated with severe complications including pneumo- and hemothorax. Data on a sole cephalic vein approach (sCV), potentially preventing these complications, are limited. The aim of our study was to compare a sole cSV with a subclavian vein approach (SV) in CRT implantations with respect to feasibility and safety. We performed a prospective cohort study enrolling twenty-four consecutive de-novo CRT implantations (group A) using a sCV at two centers. Fifty-four age-matched CRT patients implanted via the SV served (group B) as reference. Procedural success rate and complications were recorded during a follow-up of 4 weeks. All CRTs could be implanted in group A, with 91.7% using cephalic access alone. In group B, CRT implantation was successfully performed in 96.3%. Procedure and fluoroscopy duration were similar for both groups (sCV vs. SV: 119 ± 45 vs. 106 ± 31 minutes, 17 ± 9 vs 14 ± 9 minutes). Radiation dosage was higher in sCV group vs. SV (2984 ± 2370 vs. 1580 ± 1316 cGy*cm2; p = 0.001). There was no case of a pneumothorax in group of sCV, while two cases were observed using SV. Overall complication rate was similar (sCV: 13.0% vs. SV: 12.5%). de-novo CRT implantation using a triple cephalic vein approach is feasible. Procedure duration and complication rates were similar, while radiation dosage was higher in the sCV compared to the SV approach. Despite its feasibility in the clinical routine, controlled prospective studies with longer follow-up are required to elucidate a potential benefit with respect to lead longevity.