Potential utility of SPECT/CT with 99mTc-Tektrotyd for imaging of post-myocardial infarction inflammation.

BACKGROUND: There is a need to develop methods for post-myocardial infarction (MI) inflammation monitoring. Scintigraphy with somatostatin receptor targeted radiotracers has potential in this field. The purpose was to study the association of 99mTc-Tektrotyd uptake intensity in MI area with heart contractility indices over 6-month follow-up. METHODS: Fourteen patients with acute ST-segment elevation anterior MI (STEMI) were examined with 99mTc-Tektrotyd SPECT/CT, myocardial perfusion scintigraphy (MPS) at rest, cardiac magnetic resonance imaging (cMRI) and transthoracic echocardiography (TTE). Scintigraphic results were compared with 6-month TTE indices. RESULTS: On the 7th day after a MI onset, cardiac 99mTc-Tektrotyd uptake was found in 7 of 14 patients. Median of 99mTc-Tektrotyd SUVmax was 1.59 (1.38; 2.83), the summed rest score (SRS) was 11 (5; 18), infarct size (by cMRI)-13.15 (3.3; 32.2) %. 99mTc-Tektrotyd SUVmax strongly correlated with 6-month heart contractility indices (r = 0.81, P < 0.05 for the end diastolic volume; r = 0.61 P < 0.05 for Δ end diastolic volume), with SRS (r = 0.85, P < 0.05) and infarct size (by cMRI) (r = 0.79, P < 0.05). CONCLUSION: The intensity (SUVmax) of 99mTc-Tektrotyd uptake in the area of recent MI directly depends on the size of ischemic myocardial injury and correlates with changes of heart contractility indexes over the 6 month follow-up.

The value of cardiac sympathetic activity and mechanical dyssynchrony as cardiac resynchronization therapy response predictors: comparison between patients with ischemic and non-ischemic heart failure.

BACKGROUND: Impaired cardiac sympathetic activity and mechanical dyssynchrony (MD) are associated with poor prognosis in patients with heart failure (HF) after cardiac resynchronization therapy (CRT). The study aims to assess the significance of scintigraphic evaluation of cardiac sympathetic innervation and contractility in predicting response to CRT in patients with ischemic and non-ischemic chronic HF. METHODS AND RESULTS: The study includes 58 HF patients, who were referred for CRT. Prior to CRT all patients underwent 123I-metaiodobenzylguanidine (123I-MIBG) imaging and gated myocardial perfusion imaging (MPI) using a cadmium-zinc-telluride (CZT) SPECT/CT device. At a one-year follow-up post-CRT, the delayed heart-to-mediastinum 123I-MIBG uptake ratio was an independent predictor of CRT response in non-ischemic HF patients (OR 1.469; 95% CI 1.076-2.007, p = .003). In ischemic HF patients the MD index histogram bandwidth (HBW) obtained by CZT-gated MPI had a predictive value (OR 1.06, 95% CI 1.001-1.112, p = .005) to CRT response. CONCLUSION: CRT response can be predicted by cardiac 123I-MIBG scintigraphy, specifically by the heart-to-mediastinum ratio in non-ischemic HF and by the MD index HBW in ischemic HF. These results suggest the value of a potentially useful algorithm to improve outcomes in HF patients who are candidates for CRT.

Low-dose dobutamine stress gated blood pool SPECT assessment of left ventricular contractile reserve in ischemic cardiomyopathy: a feasibility study.

PURPOSE: The purpose of the present study was to evaluate the feasibility of gated blood pool single-photon emission computed tomography (GBPS) with low-dose dobutamine (LDD) stress test, performed on a single-photon emission computed tomography (SPECT) camera equipped with cadmium-zinc-telluride (CZT) solid-state detectors, in assessing of left ventricle (LV) contractile reserve in patients with ischemic cardiomyopathy (ICM). METHODS: A total of 52 patients (age 59 ± 7.2 years, 47 men and 5 women) with ICM and a control group of 10 patients without obstructive coronary artery lesion underwent GBPS and transthoracic echocardiography (TTE) at rest and during LDD stress test (5, 10, 15 µg/kg/min). The duration of each GBPS step was 5 min. Stress-induced changes in LV ejection fraction (ΔLVEF), peak ejection rate, LV volumes, and mechanical dyssynchrony (phase histogram standard deviation, phase histogram bandwidth and entropy) obtained with GBPS were estimated. RESULTS: All GBPS indices except end-diastolic volume showed significant dynamics during stress test in both groups. The majority of parameters in ICM patients showed significant changes at a dobutamine dose of 10 µg/kg/min as compared to the rest study. Seventeen percent of ICM patients, but none from the control group, showed a decrease in LVEF during stress, accompanied by a significant increase in entropy. The intra- and inter-observer reproducibility was excellent for both rest and stress studies. There was a moderate correlation (r = 0.5, p = 0.01) between GBPS and TTE, with a mean difference value of - 1.7 (95% confidence interval - 9.8; 6.4; p = 0.06) in ΔLVEF. CONCLUSION: Low-dose dobutamine stress GBPS performed with high-efficiency CZT-SPECT cameras can be performed for evaluating stress-induced changes in LV contractility and dyssynchrony with lower acquisition time. A dobutamine dose of 10 µg/kg/min can potentially suffice to detect stress-induced changes in patients with ICM during GBPS. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04508608 (August 7, 2020).

Prediction of appropriate ICD therapy in patients with ischemic heart failure.

BACKGROUND: Previous studies show inconsistent results on the role of innervation imaging (with I-123-mIBG) and perfusion imaging in predicting appropriate ICD therapy (aICDth). These studies included patients with both dilated and ischemic cardiomyopathy. This study compared the ability of 123I-mIBG imaging along with perfusion imaging (using thallium-199) to predict aICDth in patients with ischemic heart failure (IHF) in relation to indication for ICD implantation (primary vs. secondary prevention of sudden cardiac death (SCD)). METHODS: mIBG/thallium SPECT imaging were performed before ICD implantation in 80 patients with IHF: 49 candidates for primary and 31 for secondary SCD prevention. RESULTS: During a mean follow-up of 18 months, the imaging results could not predict patients with appropriate ICD therapy among patients with ICD implants for primary SCD prevention. While in the secondary SCD prevention group, those who received a ICDth had significantly larger summed scores of regional perfusion and innervation impairment, but not higher heart-to-mediastinal mIBG ratio. The best results to predict aICDth were using mIBG summed score (cut-off point > 34%, sensitivity 72%, specificity 100%, AUC 0.909, P < 0.0001). CONCLUSION: The prognostic value of innervation and perfusion imaging in patients with IHF differ based on indication for ICD implantation (primary vs. secondary prevention of SCD).

The current status of CZT SPECT myocardial blood flow and reserve assessment: Tips and tricks.

Cardiac PET-derived measurements of myocardial blood flow (MBF) and myocardial flow reserve (MFR) are proven robust indexes of the severity of coronary artery disease (CAD). They facilitate the diagnosis of diffuse epicardial and microvascular disease and are also of prognostic significance. However, low availability and high cost have limited their wide clinical implementation. Over the last 15 years, cadmium zinc telluride (CZT)-based detectors have been implemented into SPECT imaging devices. Myocardial perfusion scintigraphy can be performed faster and with less radiation exposure as compared with standard gamma cameras. Rapid dynamic SPECT studies with higher count rates can be performed. This technological breakthrough has renewed the interest in SPECT MBF assessment in patients with CAD. Currently, two cardiac-centered CZT gamma cameras are available commercially-Discovery NM530c and D-SPECT. They differ in parameters such as collimator design, number of detectors, sensitivity, spatial resolution and image reconstruction. A number of publications have focused on the feasibility of dynamic CZT SPECT and on the correlation with cardiac PET and invasive coronary angiography measurements of fractional flow reserve. Current study reviews the present status of MBF and MFR assessment with CZT SPECT. It also aims to provide an overview of specific issues related to acquisition, processing and interpretation of quantitative studies in patients with CAD.

A predictive model of super response to cardiac resynchronization therapy in short-term period.

BACKGROUND: The left bundle branch block, nonischemic heart failure (HF) and female gender are the most powerful predictors of a super response to cardiac resynchronization therapy (CRT). It is important to identify super responders who can derive most benefits from CRT. We aimed to establish a predicting model that could be used for prognosis of a super response to CRT in short-term period. METHODS: Patients with QRS ≥ 130 ms, New York Heart Association (NYHA) II-III class of HF, left ventricle ejection fraction (LVEF) ≤ 35% and indications for CRT were included in the study. Before and 6 month after CRT the electrocardiography, echocardiography and cardiac scintigraphy were performed. The study's primary endpoint was the NYHA class improvement ≥ 1 and left ventricle end systolic volume decrease > 30% or LVEF improvement > 15% after 6 month CRT. Based on collected data, we developed a predictive model regarding a super response to CRT. RESULTS: Of 49 (100.0%) patients, 32 (65.3%) had a super response to CRT. Patients with a super response were likelier to have a lower cardiac index (p = 0.007), higher rates of interventricular delay (IVD) (p = 0.003), phase standard deviation of left ventricle anterior wall (PSD LVAW) (p = 0.009) and ∆QRS (p = 0.02). Only IVD and PSD LVAW were independently associated with a super response to CRT in univariate and multivariate logistic regression. We created a logistic equation and calculated a cut-off value. The resulting ROC curve revealed a discriminative ability with AUC of 0.812 (sensitivity 90.62%; specificity 70.59%). CONCLUSION: Our predictive model is able to distinguish patients with a super response to CRT.

Predictors of appropriate therapies delivered by the implantable cardioverter-defibrillator in patients with coronary artery disease during long-term period.

This prospective study aimed to investigate the ability of cardiac autonomic nervous system (CANS) activity assessment to predict appropriate implantable cardioverter-defibrillator (ICD) therapy in patients with coronary artery disease (CAD) during long-term follow-up period. We enrolled patients with CAD and ICD implantation indications that included both secondary and primary prevention of sudden cardiac death. Before ICD implantation CANS was assessed by using heart rate variability (HRV), myocardium scintigraphy with 123I-meta-iodobenzylguanidine (123I-MIBG) and erythrocyte membranes ß-adrenoreactivity (EMA). The study's primary endpoint was the documentation of appropriate ICD therapy. Of 45 (100.0%) patients, 15 (33.3%) had appropriate ICD therapy during 36 months follow-up period. Patients with appropriate ICD therapy were likely to have a higher summed 123I-MIBG score delayed (p < 0.001) and lower 123I-MIBG washout rate (p = 0.008) indicators. These parameters were independently associated with endpoint in univariable and multivariable logistic regression. We created a logistic equation and calculated a cut-off value. The resulting ROC curve revealed a discriminative ability with AUC of 0.933 (95% confidence interval 0.817-0.986; sensitivity 100.00%; specificity 93.33%). Combined CANS activity assessment is useful in prediction of appropriate ICD therapy in patients with CAD during long-term follow-up period after device implantation.

Insights into ascending aortic aneurysm: Interactions between biomechanical properties of the aortic wall and tissue biomarkers.

Background: It remains difficult to understand the association between the local mechanical properties of ascending thoracic aorta aneurysm (asTAA), its tissue, and its cellular and molecular changes. The purpose of our study was to investigate the relationship between biomechanical properties, histopathological findings, and tissue biomarkers of asTAA. Methods: Intraoperative asTAA samples from 30 patients were studied. All samples were examined histologically and underwent a tensile test. We determined the tensile strength (σв, MPa), the strain (ε, mm/mm˟%), and the area under the strength-strain curve (S) along with the concentrations of tissue matrix metalloproteinases (MMP-1 et al.) and their inhibitors, their interleukins (IL) -6 -10, and their tumor necrosis factor (TNF) -α. Results: It was found that 43.3 % of asTAA patients had atherosclerosis, 3.3 % had aortitis, and 53.3 % of patients had connective tissue dysplasia. Differences in the studied parameters between these subgroups were not found. Age correlated with ε (r = -0.49) and S (r = -0.54). ε was also associated with media fibrosis degree (r = -0.5), collagen/elastin ratio (r = -0.61), and IL-10 (r = 0.52). IL-10 correlated with collagen/elastin ratio (r = -0.58), TNF-α (r = 0.77), and MMP-1 (r = 0.71). Conclusion: Tissue IL-10 has a protective effect on the elastic structures of the aortic wall and is positively associated with the activity of MMP-1 and pro-inflammatory cytokines. IL-6 is associated with media fibrosis degree, and negatively affects strength-strain parameters of asTAA samples.

Somatostatin Receptor Type 2 as a Potential Marker of Local Myocardial Inflammation in Myocardial Infarction: Morphologic Data on Distribution in Infarcted and Normal Human Myocardium.

Nuclear imaging modalities can detect somatostatin receptor type 2 (SSTR2) in vivo as a potential marker of local post-MI inflammation. SSTR2+ macrophages are thought to be the main substrate for SSTR-targeted radioimaging. However, the distribution of SSTR2+ cells in the MI patients' myocardium is unknown. Using immunohistochemistry, we investigated the distribution of SSTR2+ cells in the myocardium of patients who died during the MI inflammatory phase (n = 7) compared to the control group of individuals with fatal trauma (n = 3). Inflammatory cellular landscapes evolve in a wave front-like pattern, so we divided the myocardium into histological zones: the infarct core (IC), the border zone (BZ), the remote zone (RZ), and the peri-scar zone (PSZ). The number of SSTR2+ neutrophils (NPs), SSTR2+ monocytes/macrophages (Mos/MPs), and SSTR2+ vessels were counted. In the myocardium of the control group, SSTR2+ NPs and SSTR2+ Mos/MPs were occasional, SSTR2+ vessels were absent. In the RZ, the picture was similar to the control group, but there was a lower number of SSTR2+ Mos/MPs in the RZ. In the PSZ, SSTR2+ vessel numbers were highest in the myocardium. In the IC, the median number of SSTR2+ NPs was 200 times higher compared to the RZ or control group myocardium, which may explain the selective uptake of SSTR-targeted radiotracers in the MI area during the inflammatory phase of MI.

Isolated Atrial Fibrillation, Inflammation and Efficacy of Radiofrequency Ablation: Preliminary Insights Based on a Single-Center Endomyocardial Biopsy Study.

The aim of the study was to evaluate the inflammatory changes in the myocardium, based on endomyocardial biopsy (EMB) data in patients undergoing radiofrequency ablation (RFA) for idiopathic atrial fibrillation (AF). A total of 67 patients with idiopathic AF were enrolled in the study. Patients underwent the intracardiac examination, RFA of AF, and EMB with histological and immunohistochemical studies. The catheter-treatment effectiveness, and occurrence of early and late recurrences of atrial tachyarrhythmias, were assessed depending on the identified histological changes. Nine patients (13.4%) did not have any histological changes in the myocardium according to EMB. Fibrotic changes were detected in 26 cases (38.8%). Inflammatory changes according to the Dallas criteria were observed in 32 patients (47.8%). The follow-up period for patients averaged 19.3 ± 3.7 months. The effectiveness rates of primary RFA were 88.9% in patients with the intact myocardium, 46.2% in patients with fibrotic changes of varying severity, and 34.4% in patients with the presence of criteria for myocarditis. No early recurrence of arrhythmias was observed in patients with unchanged myocardia. The presence of inflammatory and fibrotic changes in the myocardium increased the rates of early and late arrhythmia recurrences and accordingly halved the effectiveness RFA of AF.

The Value of Left Ventricular Mechanical Dyssynchrony and Scar Burden in the Combined Assessment of Factors Associated with Cardiac Resynchronization Therapy Response in Patients with CRT-D.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves the outcome in patients with heart failure (HF). However, approximately 30% of patients are nonresponsive to CRT. The aim of this study was to determine the role of the left ventricular (LV) mechanical dyssynchrony (MD) and scar burden as predictors of CRT response. METHODS: In this study, we included 56 patients with HF and the left bundle-branch block with QRS duration ≥ 150 ms who underwent CRT-D implantation. In addition to a full examination, myocardial perfusion imaging and gated blood-pool single-photon emission computed tomography were performed. Patients were grouped based on the response to CRT assessed via echocardiography (decrease in LV end-systolic volume ≥15% or/and improvement in the LV ejection fraction ≥5%). RESULTS: In total, 45 patients (80.3%) were responders and 11 (19.7%) were nonresponders to CRT. In multivariate logistic regression, LV anterior-wall standard deviation (adjusted odds ratio (OR) 1.5275; 95% confidence interval (CI) 1.1472-2.0340; p = 0.0037), summed rest score (OR 0.7299; 95% CI 0.5627-0.9469; p = 0.0178), and HF nonischemic etiology (OR 20.1425; 95% CI 1.2719-318.9961; p = 0.0331) were the independent predictors of CRT response. CONCLUSION: Scar burden and MD assessed using cardiac scintigraphy are associated with response to CRT.

How to get the optimal defibrillation lead parameters using myocardial perfusion scintigraphy in patients with coronary artery disease.

The conventional criteria for a defibrillation lead (DL) implantation don't take into account presence of scar or deep ischemia in the myocardium. This may impair a proper functioning of the DL. We sought to optimize the DL implantation placement using rest myocardial perfusion scintigraphy (MPS), which allow detecting areas of myocardial hypoperfusion (MH). To study the influence of MH and scarring, detected by MPS, on the DL parameters in patients with coronary artery disease (CAD). 69 patients (male-65, age 64.8 ± 7.7 years) with CAD and indications for ICD implantation were enrolled. Two days before ICD implantation all patients underwent MPS at rest. Then patients were divided in 2 groups. In the 1st group DL was implanted considering MPS results: to the septal position, if the most significant MH were detected in the apical segments, and to the apical position, if MH were in the septal segments. In the 2nd group DL was implanted using the conventional approach without considering MPS results. Clinical 12 months follow-up was performed with ICD interrogation. Patients of both groups were comparable by clinical and scintigraphic parameters. In the same time, in the 1st group pacing threshold was lower (p < 0.0001) and ventricle signal amplitude was higher (p < 0.0001) comparing with the 2nd group at all control points. The presence of MH detected by MPS in the area of the DL placement worsens its parameters. The results of MPS in patients with CAD can be useful for optimization of DL placement.

Assessment of radiological techniques application possibility for non-invasive diagnostics of latent inflammatory processes in myocardium in patients with atrial fibrillation.

OBJECTIVE: Aim was to study the performance of single-photon emission computed tomography (SPECT) with 99mTc-pyrophosphate (99mTc-PYP) in diagnostics of chronic latent inflammation in myocardium of patients with atrial fibrillation (AF). METHODS: The research included 70 patients (the average age of 49.3 ± 10.2 years) with persistent form of idiopathic AF. All patients underwent myocardium SPECT with 99mTc-PYP and cardiac magnetic resonance imaging (CMR) before the ablation. During the ablation endomyocardium sampling for histological and immunohistochemical verification of myocarditis was performed. RESULTS: Sensitivity of SPECT with 99mTc-PYP in diagnoses of chronic latent myocarditis in patients with AF in relation to endomyocardial biopsy was 80 %, specificity-83 % and diagnostic accuracy-82 %. Sensitivity, specificity and diagnostic accuracy of myocardium perfusion scintigraphy for diagnostics of latent myocarditis in relation to endomyocardial biopsy was 30, 50 and 50 % correspondingly. Also the close correlation between the size of the perfusion defect and the severity of myocardial fibrosis in patients with AF was revealed. Specificity of the Lake Louise criteria for diagnostics of latent myocarditis in relation to endomyocardial biopsy was 77.6 %, sensitivity-60 % and diagnostic accuracy-74.5 %. For only LGE specificity was 16 %, sensitivity-90 % and diagnostic accuracy-28 %. CONCLUSIONS: The study showed the possibility of successful application of radionuclide methods for diagnoses of chronic latent myocarditis at AF. Taking into account high informative values the results of scintigraphy can be also considered as a promising additional criteria for selecting patients with AF of unexplained etiology for non-invasive endomyocardial biopsy procedure.