Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Russian Foundation for Basic Research Introduction Impaired cardiac sympathetic activity and contractility are associated with poor prognosis in patients with heart failure after cardiac resynchronization therapy (CRT). There are few prognostic data of the cardiac sympathetic activity and dyssynchrony in patients with chronic heart failure of various etiologies. Purpose To examine the prognostic significance of scintigraphic cardiac sympathetic activity and contractility in predicting the response to CRT and to assess the differences between patients with ischemic (IHF) and non-ischemic (NIHF) heart failure. Methods This study included 38 heart failure patients (24 male; mean age of 56 ± 11 years; 16 patients with ischemic etiology), who were submitted to CRT. Before CRT all patients underwent 123I-metaiodobenzylguanidine (123I-MIBG) imaging for cardiac sympathetic activity evaluating: early and delay heart to mediastinum ratio (eH/M and dH/M), summed MIBG Score (eSMS and dSMS). Moreover all patients underwent gated SPECT with the assessments of left ventricle dyssynchrony indexes: standard deviation (SD) and histogram bandwidth (HBW). In addition, all patients underwent gated blood-pool SPECT (GBPS) to assessed ejection fraction (EF) and stroke volume (SV) of both ventricles. Results One year after CRT response defined as LV ESV decreased by≥15% and/or LV EF increase by≥5%. Baseline cardiac sympathetic activity parameters showed significant differences between responders and non-responders only in NIHF patients: eH/M: 2.27 (2.02–2.41) vs. 1.64 (1.32–2.16); dH/M: 2.18 (2.11–2.19) vs. 1.45 (1.23 – 1.61); eSMS: 7 (5-7) vs. 15.5 (10–28.5); dSMS: 10 (10–13) vs. 16.5 (15.5–29). Significant differences in baseline LV dyssynchrony indexes between responders and non-responders were in patients of both group: in NIHF patients - SD: 54.3 (43–58) degree vs. 65 (62–66) degree; HBW: 179.5 (140–198) degree vs. 211 (208-213) degree, p < 0.054 in IHF patients - HBW: 162 (115.2–180) degree vs. 115.2 (79.2–136.8) degree. Contractility of RV was significantly differed between responders and non-responders in IHF patients: RV EF: 54.5 (41-56) % vs. 44.5 (37–49.5) %; RV SV: 80 (69-101) ml vs. 55.5 (50–72.5) ml. According to univariate logistic regression analyses in IHF patients LV dyssynchrony indexes – SD (OR = 1.55; 95% CI 1.09-2.2; p < 0.5) and HBW (OR = 1.13; 95% CI 1.02-1.24; p < 0.5), as well as RV indexes – RV EF (OR = 1.11; 95% CI 1.001-1.23; p < 0.5), RV SV (OR = 1.07; 95% CI 1.003-1.138; p < 0.5) were predictors of CRT response. In the group of NIHF patients, dH/M (OR = 1.47; 95% CI 1.08-2; p < 0.5), SD (OR = 0.83; 95% CI 0.73-0.95; p < 0.5), HBW (OR = 0.96; 95% CI 0.93-0.99; p < 0.5) showed the predictive value in terms of CRT response. Conclusion Scintigraphic methods can be used to select patients for CRT. Cardiac 123I-MIBG scintigraphy and gated SPECT may be used for predicting CRT response in NIHF patients. Whereas in IHF patients ECG-gated SPECT and GBPS may be valuable for predicting the response to CRT.

Aim To evaluate the predictive value of indexes of left ventricular mechanical dyssynchrony (MD) as determined by data of electrocardiogram (ECG)-gated myocardial perfusion scintigraphy (ECG-MPS) for prediction of the efficacy of resynchronization therapy (RT) in patients with chronic heart failure (CHF). Material and methods This prospective study included 32 patients with nonischemic CHF and standard indications for RT. All patients underwent complete clinical an instrumental examination, including 24-h ECG monitoring and echocardiography (EchoCG). In order to evaluate the left ventricular (LV) myocardial perfusion, contractile function, and MD, myocardial perfusion scintigraphy was performed for all patients at rest prior to RT. In addition to the perfusion defect size at rest and hemodynamic parameters, LV MD was determined. The following indexes were used for analysis of dyssynchronization: phase standard deviation (PSD), phase histogram bandwidth (HBW), and phase histogram asymmetry and steepness. The treatment efficacy was evaluated by the clinical status of patients (clinical condition evaluation scale for CHF patient) and EchoCG at 6 months following RT. The criteria for a positive response to RT were an increase in LV ejection fraction (EF) by 5% and/or a decrease in the LV end-diastolic volume by 15% compared to preoperative values. Results According to ECG-MPS findings, all patients had scintigraphic signs of severe CHF with dilated LV cavity (end-diastolic volume, EDV 246 [217; 269] ml) and also of pronounced mechanical and electrical dyssynchrony. The values of mechanical dyssynchrony were PSD 53 [41; 61], HBW 176 [136; 202], asymmetry 1.62 [1.21; 1.89], and steepness 2.81 [1.21; 3.49]. The QRS duration was 165 [155; 175] msec. Furthermore, the LV perfusion was moderately impaired (perfusion defect size 4 [3; 10] %). Mean follow-up duration after implantation of the resynchronizing device was 6±1.7 mos. According to the selected criteria, 20 (63 %) patients were considered as responders and 12 (37 %) patients as non-responders. Before implantation of the cardiac synchronizing device, responders and non-responders differed only in LV MD (PSD 44 [35; 54] vs. 63 [58; 72]; p=0.0001); HBW 158 [118; 179] vs. 205 [199; 249]; p=0.0001; asymmetry 1.77 [1.62; 2.02] vs. 1.21 [0.93; 1.31]; p=0.0001; steepness 3.03 [2.60; 3.58] vs. 1.21 [0.19; 1.46]; p=0.0001), respectively. A one-factor logistic regression analysis showed that MD values were statistically significant predictors of a positive response to RT. A multi-factor logistic analysis of phase histogram steepness (odds ratio, OR 1.196; 95 % confidence interval, CI 1.04–1.37) and PSD (OR 0.67; 95 % CI 0.47–0.97) were identified as independent predictors for the response to RT. According to results of the ROC analysis, a PSD <55 and a phase histogram steepness >1.54 may predict the effectiveness of RT (AUC= 0.92; р=0.0001). Conclusion LV MD parameters determined with ECG-MPS allow predicting the effectiveness of RT in patients with nonischemic CHF. In this patient group, high values of standard deviation and low values of phase histogram steepness were independent predictors for the absence of response to RT after 6 mos. of follow-up.

Cardiac resynchronization therapy (CRT) is one of the methods of treating patients with chronic heart failure, which can reduce the mortality rate of this group. Scintigraphic assessment of sympathetic myocardial innervation allows us to evaluate the heart failure prognosis and the effectiveness of interventional treatment. The method is based on use of the radiopharmaceutical 123 I-methiodiobenzylguanidine (123 I-MIBG), which is a structural analogue of norepinephrine and is able to selectively accumulate in the sympathetic nerve endings. This review includes a brief description of norepinephrine metabolism and pharmacokinetics of 123 I-MIBG in the sympathetic nerve ending, a brief description of the study methodology and the clinical significance of this method in patients with heart failure. Particular attention is paid to the possibilities of using this method in patients with severe chronic heart failure before and after CRT.

Abstract Introduction In chronic heart failure patients, cardiac resynchronization therapy (CRT) does not lead to the expected result in 30% of cases. There is a lack of prognostic data related to the cardiac sympathetic activity and contractility assessment in ischemic (IHF) and non-ischemic (CHF) heart failure patients. Purpose To assess the prognostic value of radionuclide cardiac sympathetic innervation and contractility assessment in IHF and NIHF patients submitted to CRT. Methods This study included 38 HF patients (24 male; mean age of 56±11 years), who were submitted to CRT: NYHA class II/III (n=10/28), mean QRS=159.3±17.9ms. The etiology of HF was ischemic in 16 patients and non-ischemic in 22 of them. Before CRT all patients underwent 123I-metaiodobenzylguanidine (123I-MIBG) imaging for cardiac sympathetic activity evaluating. The following indexes were estimated: early and delayed heart to mediastinum ratio (eH/M and dH/M), summed MIBG Score (eSMS and dSMS). Moreover all patients underwent gated myocardial perfusion scintigraphy with the assessments of LV dyssynchrony indexes: standard deviation (SD) and histogram bandwidth (HBW). In addition, all patients underwent gated blood-pool SPECT with both ventricles ejection fraction (EF) and stroke volume (SV) assessment. Results One year after CRT all patients were divided into two groups: responders (IHF group n=11; NIHF group n=15) and non-responders (IHF group n=5; NIHF group n=7). Among baseline scintigraphic parameters the following ones showed significant differences between responders vs. non-responders. In IHF patients - HBW: 162 (115.2–180) degree vs. 115.2 (79.2–136.8) degree, p<0.05; RV_EF: 54.5 (41–56)% vs. 44.5 (37–49.5)%, p<0.05; RV_SV: 80 (69–101)ml vs. 55.5 (50–72.5)ml, p<0.05. In group of NIHF patients responders and non-responders were significantly differed in the following preoperative parameters: eH/M: 2.27 (2.02–2.41) vs. 1.64 (1.32–2.16), p<0.05; dH/M: 2.18 (2.11–2.19) vs. 1.45 (1.23–1.61), p<0.05; eSMS: 7 (5–7) vs. 15.5 (10–28.5), p<0.05; dSMS: 10 (10–13) vs. 16.5 (15.5–29), p<0.05, SD: 54.3 (43–58) degree vs. 65 (62–66) degree, p<0.05; HBW: 179.5 (140–198) degree vs. 211 (208–213) degree, p<0.05. Univariate logistic regression in IHF patients showed that LV dyssynchrony indexes – SD (OR=1.55; 95% CI 1.09–2.2; p<0.5) and HBW (OR=1.13; 95% CI 1.02–1.24; p<0.5), as well as RV indexes – RV_EF (OR=1.11; 95% CI 1.001–1.23; p<0.5), RV_SV (OR=1.07; 95% CI 1.003–1.138; p<0.5) were predictors of CRT response. In the group of NIHF patients, dH/M (OR=1.47; 95% CI 1.08–2; p<0.5), SD (OR=0.83; 95% CI 0.73–0.95; p<0.5), HBW (OR=0.96; 95% CI 0.93–0.99; p<0.5) showed the predictive value in terms of CRT response. Conclusion(s) The positive response to CRT in IHF patients showed a link with LV dyssynchrony and preserved RV contractility. Whereas in NIHF patients the functional state of cardiac sympathetic activity, as well as LV dyssynchrony, were associated with CRT response. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Russian Foundation for Basic Research

AIM:To determine the effect of right ventricular myocardial contractility on the response to cardiac resynchronization therapy (CRT).MATERIALS AND METHODS:The study included 80 patients (49 men, mean age 54±10.5) diagnosed with dilated cardiomyopathy, complete left bundle branch block, and the QRS complex width 146 to 240 ms (183±32 ms). Heart failure was NYHA FC III, ejection fraction (EF) - 30.1±3.8 %, 6‑min walk test - 290.5±64.3 m, and end-diastolic volume (EDV) - 220.7±50.9 ml. 35 patients had permanent atrial fibrillation. All patients received implantable devices for CRT; complete artificial atrioventricular block was formed in patients with atrial fibrillation. LV and right ventricular (RV) contractile function was studied in all patients before and at 12 months of the implantation using equilibrium radionuclide tomoventriculography.RESULTS:At 12 months, 69 (86.25 %) patients were clinical responders to CRT and 11 (13.75 %) patients did not respond to the treatment. The responders showed positive clinical dynamics; LV EF increased from 30.1±3.8 to 42.8±4.8 % (p≤0.001), LV EDV decreased from 220.7±50.9 to 197.9±47.8 ml (p≤0.005). In non-responders, LV EF increased from 30.1±3.8 to 33.8±3.8 % (p≤0.001) and LV EDV increased from 220.7±50.9 to 227.8±27.8 ml (p≤0.001). All patients were retrospectively divided into two groups: Group 1, CRT responders and Group 2, non-responders. A study using radionuclide methods showed that in Group 1 patients, maximum RV filling velocity increased from 1.8±0.36 to 2.17±0.67 (p≤0.001) and the mean velocity of RV filling for one third of diastole increased from 1±0.28 to 1.32±0.45 (p≤0.001). In Group 2, these parameters were significantly worse by 30 and 60 %, respectively.CONCLUSIONS:Cardiac resynchronization therapy is more effective in preserved contractility of the right heart, and higher values of maximum RV filling velocity for one third of diastole may serve a prognostic criterium for a beneficial response to CRT.