Ventricular Myocardial Perfusion Research Articles

Intra-Interobserver Variability in Myocardial Perfusion and Function Interpretation and Reproducibility of QGS/QPS Software

Aim: To assess three different level experienced nuclear medicine specialists’ intra- and interobserver variability of semiquantitative visual interpretations of left ventricular (LV) myocardial perfusion, wall motion (WM), and wall thickening (WT) in gated myocardial perfusion single- photon emission tomography (gMPS), and to compare the compatibility between the observers’ and coronary angiography (CAG) reports. Methods: A 5-point perfusion scale, a 6-point scale for WM, and a 4-point scale for WT were used to score each segment. The images were interpreted 3 times at least one-month intervals separately by 3 observers. Subsequently, the visual semiquantitative summed scores for stress (SSS) and rest (SRS) were calculated by summing the respective segmental perfusion scores. Summed difference score (SDS) was also calculated as the difference between SSS and SRS. Both visual semiquantitative WM and WT scores were calculated from the stress images by summing all corresponding segmental scores. Results: Intraobserver agreement in the evaluation of global perfusion was statistically significant (71.9-100 %). There was a significant agreement in all LAD-SSS, Cx-SSS, ve RCA-SSS interpretations. There was good agreement between 3 readings of 3 observers' (p=0.0). Due to the high interobserver agreement levels in the global evaluation, the mean values of the 1. and the 2. interpretations (mean 1.-2. int.) were calculated and regional comparisons were made with this new value and the 3. interpretation. There was a a significant agreement in 3 of the regional SSS interpretations. Although lowest agreement rates were calculated in LAD artery territory, the agreement levels were statistically, and highly significant in all territories. In both Cx and RCA territories, the agreement levels were statistically significant (p

Impaired myocardial energetics in both sarcomere positive and negative HCM are linked to arrhythmic risk

Abstract Background Impaired myocardial energetics play a pivotal role in the complex pathophysiology of hypertrophic cardiomyopathy (HCM), and are thought to be mediated by energy-costly sarcomeric mutations and mitochondrial dysfunction (1). Two thirds of HCM patients, however, do not possess pathogenic sarcomeric mutations (2) and instead develop the condition due to a combination of increased polygenic susceptibility and comorbidities. Whether energetic impairment, a target of novel HCM treatments (e.g., myosin modulators such as Mavacamten), similarly affects sarcomere mutation positive (Sarc+) and negative (Sarc-) HCM remains unclear, as does the association between impaired energetics and markers of arrhythmic risk such as hypertrophy severity, cardiac function and non-sustained ventricular tachycardia (NSVT). This study aimed to investigate differences in resting myocardial energetics between Sarc+ and Sarc- HCM by measuring the phosphocreatine-to-adenosine triphosphate (PCr/ATP) ratio using phosphorus magnetic resonance spectroscopy (31P-MRS) and explore the association between impaired energetics and markers of arrhythmic risk in HCM. Methods We recruited one hundred (100) participants (80 non-obstructive HCM patients and 20 age- and sex-matched controls). Myocardial energetics were assessed using 31P-MRS to measure the PCr/ATP ratio. Cardiac magnetic resonance (CMR) imaging including cine, T1 (ShMOLLI), quantitative pixel-wise perfusion mapping (3) and late gadolinium enhancement (LGE) imaging was also performed. In addition, HCM patients underwent 7-day ECG monitoring to document NSVT episodes (3 beats ≥120 bpm). Results HCM patients had impaired myocardial energetics (PCr/ATP ratio) relative to controls (HCM 1.64±0.36 vs controls 1.97±0.32 p<0.001). PCr/ATP ratios did not differ between Sarc+ and Sarc- HCM even after adjustment for confounders including age, hypertrophy and fibrosis burden (Sarc+ 1.64 [1.50-1.78] vs Sarc- 1.64 [1.52-1.77], p=0.993). PCr/ATP ratio showed no correlation with maximum wall thickness (p=0.257), left ventricular ejection fraction (p=0.727) or myocardial perfusion reserve (p=0.851), but did inversely correlate with global longitudinal strain (r=-0.3, p=0.025). Reduced PCr/ATP was associated with presence of fibrosis (LGE+ 1.58±0.35 vs LGE- 1.79±0.37 p=0.025) and with NSVT, independent of age or fibrosis burden (NSVT+ 1.54 [1.40-1.67] vs NSVT- 1.73 [1.62-1.86], p=0.046). Conclusion Myocardial energetics are similarly impaired in Sarc+ and Sarc- HCM, and are independently associated with impaired contractility, greater fibrosis severity and heightened arrhythmic risk. Our findings provide novel mechanistic insights into the potentially favourable response of HCM patients to energy-sparing myosin modulator therapies irrespective of genotype and highlight the potential for cardiac energetics to serve as a marker of arrhythmic risk.

Comparison of left ventricular myocardial perfusion parameters according to adenosine triphosphate stress computed tomography myocardial perfusion with clinical parameters of patients with nonobstructive coronary artery disease

Comparison of left ventricular myocardial perfusion parameters according to adenosine triphosphate stress computed tomography myocardial perfusion with clinical parameters of patients with nonobstructive coronary artery disease

A novel algorithm developed using machine learning and a J-ACCESS database can estimate defect scores from myocardial perfusion single-photon emission tomography images.

Stress myocardial perfusion single-photon emission computed tomography (SPECT) imaging (MPI) has been used to diagnose and predict the prognoses of patients with coronary artery disease (CAD). An ongoing multicenter collaboration established a Japanese database (J-ACCESS) in 2001 that includes a risk model and expert interpretations. The present study aimed to develop a novel algorithm using machine learning (ML) and resources from the J-ACCESS database to aid SPECT image interpretation. We analyzed data from 1288 patients in J-ACCESS 3 and 4 databases. Three-dimensional (3D) stereoscopic images of left ventricular myocardial perfusion were reconstructed with linear transformation from the original short-axis data. Segments were extracted from U-Net, then features were extracted from each segment during the ML process. We estimated segmental scores based on weighted features obtained from fully connected layers. Correlations between segment scores interpreted by nuclear cardiology experts and estimated by ML were evaluated using a 17-segment model, summed stress (SSS), summed rest (SRS), and summed difference (SDS) scores, and ratios (%) of summed different scores (%SDS). The complete concordance rate of scores assessed by the experts and estimated by ML was 79.6%. The underestimated and overestimated rates were 10.3% and 10.0%, respectively. Associations between defect scores assessed by experts and ML were close, with correlation coefficients (r) of 0.923, 0.917, 0.842 and 0.853 for SSS, SRS, SDS, %SDS, respectively (p < 0.0001 for all). We created a new algorithm to estimate MPI scores using ML and the J-ACCESS database. This algorithm should provide accurate MPI interpretation even in facilities without specialist nuclear cardiologists, and might facilitate therapeutic decision-making and predict prognoses.

Impact of pretransplant T2DM on left ventricular deformation and myocardial perfusion in heart transplanted recipients: a 3.0 T cardiac magnetic resonance study

BackgroundPretransplant type 2 diabetes mellitus (T2DM) is associated with increased cardiovascular and all-cause mortality after heart transplant (HT), but the underlying causes of this association remain unclear. The purpose of this research was to examine the impact of T2DM on left ventricular (LV) myocardial deformation and myocardial perfusion following heart transplantation using cardiovascular magnetic resonance imaging.MethodsWe investigated thirty-one HT recipients with pretransplant T2DM [HT(DM+)], thirty-four HT recipients without pretransplant T2DM [HT(DM−)] and thirty-six controls. LV myocardial strains, including the global longitudinal, radial, and circumferential strain (GLS, GRS and GCS, respectively), were calculated and compared among groups, as were resting myocardial perfusion indices, which included time to peak myocardial signal intensity (TTM), maximum signal intensity (MaxSI), and Upslope. The relationships between LV strain parameters or perfusion indices and biochemical indicators were determined through Spearman’s analysis. The impact of T2DM on LV strains in HT recipients was assessed using multivariable linear regression analyses with backward stepwise selection.ResultsIn the HT(DM+) group, the LV GLS, GRS, and GCS exhibited significantly lower magnitudes than those in both the HT(DM−) and control groups. TTM was higher in the HT(DM+) group than in both the HT(DM−) and control groups, while no significant differences were observed among the groups regarding Upslope and MaxSI. There was a negative correlation between glycated hemoglobin and the magnitude of strains (longitudinal, r = − 0.399; radial, r = − 0.362; circumferential, r = − 0.389) (all P < 0.05), and a positive correlation with TTM (r = 0.485, P < 0.001). Regression analyses that included both pretransplant T2DM and perfusion indices revealed that pretransplant T2DM, rather than perfusion indices, was an independent determinant of LV strain (β = longitudinal, − 0.508; radial, − 0.370; circumferential, − 0.371) (all P < 0.05).ConclusionIn heart transplant recipients, pretransplant T2DM has a detrimental effect on subclinical left ventricular systolic function and could potentially impact myocardial microcirculation following HT.

Ultrasound study of right ventricular myocardial perfusion and functional changes in hypertrophic cardiomyopathy.

To evaluate the changes of right ventricular (RV) myocardial perfusion and function in patients with hypertrophic cardiomyopathy (HCM) by myocardial contrast echocardiography (MCE) and speckle tracking (2D-STE), and to explore the relationship between RV myocardial perfusion and strain. Conventional ultrasound, MCE and 2D-STE were performed on 29 HCM patients and 21 healthy subjects to analyze RV myocardial perfusion, RV global strain, RV free wall strain, and strain of each segment. The correlation between RV myocardial perfusion and strain was further analyzed in HCM patients. MCE results showed that the regional myocardial perfusion of the RV in HCM patients was decreased. Compared with the normal control group, the mean slope (β) in the middle and apical segments of the RV free wall, and the peak intensity (A), β, myocardial blood flow (MBF) of the ventricular septum decreased in HCM patients (P < 0.05). RV function was impaired in HCM patients. The RV global strain (RV GLS), and the strain of RV free wall and each segment were lower than those in the normal control group (P < 0.05). Correlation analysis showed that there was a certain correlation between RV myocardial perfusion and strain, such as the β of the whole RV in HCM group had a positive correlation with the strain of the middle segment of the interventricular septum (r = 0.550, P = 0.002). The regional myocardial perfusion and strain of the RV in HCM patients are reduced, and there is a positive correlation between them, suggesting that the reduction of myocardial strain may be related to the impairment of myocardial microcirculation.

Virtual platform for computer simulation of radionuclide imaging in nuclear cardiology: Comparison with clinical data

BACKGROUND: In radionuclide imaging, in vivo human clinical studies are limited because of radiation exposure and ethical concerns; therefore, mathematical modeling and in silico computer simulations based on digital models are becoming increasingly important. In the English-language literature, this approach is called “virtual clinical trials.” AIMS: This study aimed to develop software tools for the simulation of radionuclide visualization of myocardial perfusion by single-photon emission computed tomography combined with computed tomography using 99mTc-MIBI as the radiopharmaceutical and perform studies aimed at improving the accuracy of single-photon emission computed tomography. MATERIALS AND METHODS: A software package “Virtual platform for simulations of single-photon emission computed tomography combined with computed tomography method in nuclear cardiology” was developed using digital patient models, a scanner, and assessment of the state of the myocardium using digital images of the left ventricle in the form of a “polar map.” Verification of the software package was performed by comparison with clinical data obtained at the National Medical Research Center of Cardiology Named After Academician E.I. Chazov (Moscow). Simulation computer tests were performed, in which the accuracy of assessing the state of the myocardium was assessed, depending on the approach to normalizing the polar map and corrective factors in the reconstruction algorithm. RESULTS: The results of the simulation tests revealed that the assessment of left ventricular myocardial perfusion significantly depended on the method of normalizing the polar map and considered corrective factors in the reconstruction algorithm. The most accurate estimates were obtained by calculating the normalization coefficient from the average value of activity in the normal zone of the myocardium. The common approach to pixel normalization with maximum intensity can lead to errors. The results of the virtual trials were fully consistent with clinical observations. CONCLUSIONS: The transition from relative normalized values of activity in the myocardium to absolute quantitative estimates may eliminate existing limitations and uncertainties and is the main condition for improving the diagnostic accuracy of single-photon emission computed tomography combined with computed tomography in nuclear cardiology.

Diagnosis, performance and added value of assessing ventricular dyssynchrony by phase analysis in patients with three-vessel disease: A single-center cross-sectional study in Mexico

BackgroundThree-vessel disease (3VD) is a cardiovascular disorder that affects the three main coronary arteries. Gated myocardial perfusion SPECT (GMPS) evaluates ventricular function, synchrony, and myocardial perfusion. However, the diagnostic performance of GMPS parameters to assess 3VD has not been fully explored. AimsTo assess the univariate performance capacity of GMPS parameters, and to evaluate whether phase parameters could provide additional predictive value for the detection of patients with 3VD compared to control subjects. MethodsWe designed paired retrospective samples of GMPS images of patients with 3VD (stenosis > 70% of left anterior descending, right coronary, and circumflex coronary arteries) and without 3VD. A GMPS in rest-stress protocol was performed using 99mTc-Sestamibi and thallium and analyzed with the 3D method. Area under the receiver-operating characteristic curves (AUROC), decision curve analyses and diagnostic test performance were obtained for univariable analyses and stepwise binomial logistic regression for multivariable performance. Results474 Patients were included: 237 with 3VD (84% males, mean age 61.7 ± 9.9 years) and 237 with normal GMPS (51% women, mean age 63.8 ± 10.6 years). The highest AUROC for perfusion parameters were recorded for SSS, SRS and TID. For dyssynchrony parameters, both entropy and bandwidth in rest and stress phases displayed the highest AUROC and diagnostic capacity to detect 3VD. A multivariate model with SRS ≥ 4, SDS ≥ 2, TID > 1.19 and sBW ≥ 48° displayed the highest diagnostic capacity (0.923 [95% CI 0.897-0.923]) to detect 3VD. ConclusionPerfusion and dyssynchrony were the parameters which were most able to discriminate patients with 3VD from those who did not have CAD.

Changes in myocardial perfusion according to left ventricular pacing site in cardiac resynchronization therapy

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): 1. The Danish Heart Foundation 2. The Health Research Fund of the Central Denmark Region Background/Introduction Changes in left ventricular (LV) myocardial perfusion according to LV pacing site during cardiac resynchronization therapy (CRT) has only been sparsely described. Purpose To assess changes in LV global and regional myocardial perfusion according to LV pacing site after six months CRT. Methods Data from patients enrolled in the randomized controlled trial "Electrically vs. Imaging-guided Left Ventricular Lead Placement in Cardiac Resynchronization Therapy" was evaluated. Global and segmental absolute myocardial perfusion in ml/g/min was assessed by 82Rb-PET the day before CRT implantation and at six-months follow-up (6MFU). The exact LV pacing site was determined by post-implant cardiac CT. Perfusion and pacing site were evaluated using the standard 17’-segment LV model. Echocardiographic assessment of LV ejection fraction (EF) was performed the day before CRT implantation and at 6MFU. Results 93 patients (age 71±9 years; ischemic heart disease 48%; female 25%; median QRS 166±20 ms; mean LVEF 30±7%; NYHA class I/II/III/IV (%) 0/63/33/3) were included. Distribution of LV pacing sites is shown in Figure 1. No change in LV global perfusion was observed from baseline to 6MFU (0.79 to 0.81 ml/g/min, P=0.41; respectively). LV EF increased by 9±10%. Baseline global perfusion was higher in the 39 patients in whom LV EF had increased ≥10% at 6MFU (0.86 vs. 0.74 ml/g/min, P=0.02; respectively). However, no difference in perfusion-change was observed between patients with ≥10% increase in LV EF at 6MFU and patients with &amp;lt;10% increase (0.01 vs. 0.02 ml/g/min, P=0.76; respectively). Baseline perfusion was higher in the segments chosen for LV-pacing than in the non-paced segments (0.96 vs. 0.78 ml/g/min, P=0.00; respectively). Perfusion in the paced segments dropped to 0.86 ml/g/min (P=0.00) at 6MFU. Perfusion in the neighbouring segments also dropped during six months (from 0.91 to 0.86 ml/g/min, P=0.03), while perfusion in the non-paced and non-neighbouring segments increased (from 0.75 to 0.80 ml/g/min, P=0.01). Conclusion Despite a mean increase in LV EF of 9%, global myocardial perfusion remained unchanged. CRT resulted in a homogenous distribution of myocardial perfusion with a decreased perfusion in segments concordant and adjacent to LV pacing site and a corresponding increased perfusion in remote segments.

Association of Epicardial Adipose Tissue With Left Ventricular Strain and MR Myocardial Perfusion in Patients With Known Coronary Artery Disease.

Epicardial adipose tissue (EAT) may have a paracrine effect on coronary microcirculation and myocardium. However, it is unclear whether EAT is linked to cardiac function and perfusion. To investigate the association of EAT with left ventricular (LV) strain and myocardial perfusion in patients with coronary artery disease (CAD). Retrospective. A total of 78 patients with CAD and 20 healthy controls. The patients were further divided into high (n=39) and low EAT volume (n=39) groups according to median EAT volume. A 1.5 T, balanced steady-state free precession, inversion recovery prepared echo-planar, and segmented-turbo fast low-angle shot (FLASH) phase-sensitive inversion recovery (PSIR) sequences. EAT volume was measured by manually tracing the epicardial border and the visceral layer of pericardium on the short-axis cine stacks. LV strain parameters included global radial (GRS), circumferential (GCS), and longitudinal peak strain (GLS). Perfusion indices included upslope, perfusion index, time-to-maximum signal intensity (TTM), and maximum signal intensity (MaxSI). One-way analysis of variance or Kruskal-Wallis rank tests, Chi-squared or Fisher exact tests. Multivariate linear regression analyses. A P value < 0.05 was considered statistically significant. The parameters of GRS GCS, GLS, upslope, perfusion index, and MaxSI were significantly lower in the patients when compared to the controls. Moreover, the high EAT volume group presented significantly longer TTM values and lower GRS, GCS, GLS, upslope, perfusion index, and MaxSI than the low EAT volume group. Multivariate linear regression analyses demonstrated that EAT was independently associated with GRS, GCS, GLS, upslope, perfusion index, TTM, and MaxSI in patients. EAT and upslope were independently associated with GRS, while EAT and perfusion index were both independently associated with GCS and GLS. EAT was associated with parameters of LV function and perfusion, and myocardial perfusion was independently associated with LV strain in patients with CAD. 3. Stage 3.

Subclinical Systemic Sclerosis Primary Heart Involvement by Cardiovascular Magnetic Resonance Shows No Significant Interval Change.

Subclinical systemic sclerosis (SSc) primary heart involvement is commonly described. Whether these findings progress over time is not clear. The study aimed to investigate cardiovascular magnetic resonance (CMR) interval change of subclinical SSc primary heart involvement. Patients with SSc with no cardiovascular disease underwent two CMR scans that included T1 mapping and quantitative stress perfusion. The CMR change (mean difference) and association between CMR measures and clinical phenotype were assessed. The study had a prospective design. Thirty-one patients with SSc participated, with a median (interquartile range) follow-up of 33 (17-37) months (10 [32%] in the diffuse subset, 16 [52%] with interstitial lung disease [ILD], and 11 [29%] who were Scl-70+). Four of thirty-one patients had focal late gadolinium enhancement (LGE) at visit 1; one of four had an increase in LGE scar mass between visits. Two patients showed new focal LGE at visit 2. No change in other CMR indices was noted. The three patients with SSc with increased or new LGE at visit 2 had diffuse cutaneous SSc with ILD, and two were Scl-70+. A reduction in forced vital capacity and total lung capacity was associated with a reduction in left ventricular ejection fraction (ρ= 0.413, P= 0.021; ρ= 0.335, P= 0.07) and myocardial perfusion reserve (MPR) (ρ= 0.543, P= 0.007; ρ= 0.627, P= 0.002). An increase in the N-terminal pro-brain natriuretic peptide level was associated with a reduction in MPR (ρ= -0.448, P= 0.042). Patients on disease-modifying antirheumatic drugs (DMARDs) had an increase in native T1 (mean [SD] 1208 [65] vs. 1265 [56] milliseconds, P= 0.008). No other clinically meaningful CMR change in patients receiving DMARDs or vasodilators was noted. Serial CMR detects interval subclinical SSc primary heart involvement progression; however, this study suggests abnormalities remain largely stable with follow-up.

ECHO provides layer-specific insight of both myocardial deformation and microcirculation dysfunction in dilated cardiomyopathy patients: Clinical value of combined application of left ventricular layer-specific strain and myocardial contrast echocardiography.

To investigate the pattern of left ventricular (LV) function and myocardial perfusion and their relationship in dilated cardiomyopathy (DCM) patients using layer-specific speckle tracking imaging (STI) and layer-specific myocardial contrast echocardiography (MCE). Thirty DCM patients and 30 controls were recruited and underwent STI and MCE examination. The peak values of longitudinal strain (LS), circumferential strain (CS) of each layer of LV were recorded and compared between groups. Additionally, cross-sectional area of a microvessel (A) and average myocardial microvascular lesion (β) of each layer were measured, myocardial blood flow (MBF) was estimated using A × β, above parameters were compared between two groups. The LS of endo- (LSendo ), mid- (LSmid ) and epicardium (LSepi ), as well as CS of endo- (RSendo ), mid- (RSmid ), (LSepi ) epicardium and LS endo/epi, CS endo/epi were significantly decreased in DCM patients. More importantly, DCM patients demonstrated decreased A, β and A × β in all three myocardium layers and A endo/epi, β endo/epi, A × β endo/epi compared to the controls. The time to peak and the cardiac cycle required to reach the peak were prolonged in DCM patients (p < 0.05). Longitudinal strain parameters of each layer had a negative relationship with perfusion parameter A and this relationship was strongest between LSendo and Aendo (r=0.690, p < 0.01). The cardiac strain and, more importantly, coronary microcirculation perfusion was impaired in each layer in DCM patients. The longitudinal function of the LV myocardium was closely related to changes in myocardial microcirculation perfusion.

Frontiers of COVID-19-related myocarditis as assessed by cardiovascular magnetic resonance.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In some patients, COVID-19 is complicated with myocarditis. Early detection of myocardial injury and timely intervention can significantly improve the clinical outcomes of COVID-19 patients. Although endomyocardial biopsy (EMB) is currently recognized as the ‘gold standard’ for the diagnosis of myocarditis, there are large sampling errors, many complications and a lack of unified diagnostic criteria. In addition, the clinical methods of treating acute and chronic COVID-19-related myocarditis are different. Cardiac magnetic resonance (CMR) can evaluate the morphology of the heart, left and right ventricular functions, myocardial perfusion, capillary leakage and myocardial interstitial fibrosis to provide a noninvasive and radiation-free diagnostic basis for the clinical detection, efficacy and risk assessment, and follow-up observation of COVID-19-related myocarditis. However, for the diagnosis of COVID-19-related myocarditis, the Lake Louise Consensus Criteria may not be fully applicable. COVID-19-related myocarditis is different from myocarditis related to other viral infections in terms of signal intensity and lesion location as assessed by CMR, which is used to visualize myocardial damage, locate lesions and quantify pathological changes based on various sequences. Therefore, the standardized application of CMR to timely and accurately evaluate heart injury in COVID-19-related myocarditis and develop rational treatment strategies could be quite effective in improving the prognosis of patients and preventing potential late-onset effects in convalescent patients with COVID-19.

Sonothrombolysis Promotes Improvement in Left Ventricular Wall Motion and Perfusion Scores after Acute Myocardial Infarction.

ResumoFundamentoDemonstrou-se recentemente que a aplicação de ultrassom de alta energia com microbolhas, técnica conhecida como sonotrombólise, causa a dissolução de trombos intravasculares e aumenta a taxa de recanalização angiográfica no infarto agudo do miocárdio com supradesnivelamento do segmento ST (IAM-CSST).ObjetivoAvaliar o efeito da sonotrombólise nos índices de motilidade e perfusão miocárdicas em pacientes com IAM-CSST, utilizando a ecocardiografia com perfusão miocárdica em tempo real (EPMTR).MétodoUma centena de pacientes com IAM-CSST foram randomizados em dois grupos: Terapia (50 pacientes tratados com sonotrombólise e angioplastia coronária primária) e Controle (50 pacientes tratados com angioplastia coronária primária). Os pacientes realizaram EPMTR para analisar a fração de ejeção do ventrículo esquerdo (FEVE), o índice de escore de motilidade segmentar (IEMS) e o número de segmentos com defeito de perfusão miocárdica, 72 horas após o IAM-CSST e com 6 meses de acompanhamento. Foi considerado significativo p < 0,05.ResultadosPacientes tratados com sonotrombólise apresentaram FEVE mais alta que o grupo Controle em 72 horas (50 ± 10% vs. 44 ± 10%; p = 0,006), e essa melhora foi mantida em seis meses (53 ± 10% vs. 48 ± 12%; p = 0,008). O IEMS foi similar nos grupos Terapia e Controle em 72 horas (1,62 ± 0,39 vs. 1,75 ± 0,40; p = 0,09), mas tornou-se menor no grupo Terapia em 6 meses (1,46 ± 0,36 vs. 1,64 ± 0,44; p = 0,02). O número de segmentos com defeito de perfusão não foi diferente entre os grupos em 72 horas (5,92 ± 3,47 vs. 6,94 ± 3,39; p = 0,15), mas ficou menor no grupo Terapia em 6 meses (4,64 ± 3,31 vs. 6,57 ± 4,29; p = 0,01).ConclusãoA sonotrombólise em pacientes com IAM-CSST resulta na melhora dos índices de motilidade e perfusão ventricular ao longo do tempo.

Nuklearmedizinische Funktionsdiagnostik in der Kardiologie

Cardiac nuclear medicine comprises various diagnostic techniques using radiopharmaceuticals for functional imaging in vivo. This article provides an overview of current clinical use of cardiac imaging in nuclear medicine in Germany: Myocardial perfusion imaging using SPECT is a well-established noninvasive tool to semi-quantitatively measure left ventricular myocardial perfusion. Ischemia and chronic myocardial scars can be idenified with a high diagnostic accuracy. Gated SPECT enables measuring left ventricular function. With new dedicated solid-state camera systems examinations have become faster and better while radiation exposure has been minimized. These new camera systems allow quantitative calculations of myocardial blood flow, which will further improve diagnostic accuracy.For patients with severe chronic coronary artery disease and myocardial dysfunction analyzing myocardial viability is crucial for guiding therpeutic decisions. For detection of hibernating myocardium and its differentiation from scar tissue, two nuclear cardiac methods are combined: Rest myocardial perfusion imaging detects perfusion defects and cardiac 18F-FDG-PET/CT detects glucose metabolism in the hypoperfused area. As long as glucose metabolism is intact therapeutic interventions can be beneficial.In general 18F-FDG-PET/CT allows visualization and quantification of celluar glucose metabolism in oncologic and inflammatory processes. For analysis of cardiac inflammation (e. g. endocarditis or sarcoidosis) a no-carb and high-protein diet is needed at leat 24 hours prior to imaging in order to suppress the physiologic myocardial glucose metabolism. Then, specific inflammatory tracer uptake can be assessed.Cardiac amyloidosis is a rare but dangerous condition. With a specific amyloidosis scintigraphy (bone scintigraphy), cardiac ATTR-amyloidosis can be diagnosed with high accuracy. A potenitally harmful myocardial biopsy often is not needed any more and specific therapy can be initiated.In summary, diagnostic methods in cardiac nuclear medicine non-invasively allow visualization and function analysis of biological processes and are essential for diagnosis finding and therapy guidance. The continuous advancement of diagnostic tools makes nuclear cardiology a highly relevant and interesting field.

Developmental endothelial locus-1 protects from hypertension-induced cardiovascular remodeling via immunomodulation.

The causative role of inflammation in hypertension-related cardiovascular diseases is evident and calls for development of specific immunomodulatory therapies. We tested the therapeutic efficacy and mechanisms of action of developmental endothelial locus-1 (DEL-1), an endogenous antiinflammatory factor, in angiotensin II– (ANGII–) and deoxycorticosterone acetate–salt–induced (DOCA-salt–induced) cardiovascular organ damage and hypertension. By using mice with endothelial overexpression of DEL-1 (EC-Del1 mice) and performing preventive and interventional studies by injecting recombinant DEL-1 in mice, we showed that DEL-1 improved endothelial function and abrogated aortic adventitial fibrosis, medial thickening, and loss of elastin. DEL-1 also protected the mice from cardiac concentric hypertrophy and interstitial and perivascular coronary fibrosis and improved left ventricular function and myocardial coronary perfusion. DEL-1 prevented aortic stiffness and abolished the progression of hypertension. Mechanistically, DEL-1 acted by inhibiting αvβ3 integrin–dependent activation of pro-MMP2 in mice and in human isolated aorta. Moreover, DEL-1 stabilized αvβ3 integrin–dependent CD25+FoxP3+ Treg numbers and IL-10 levels, which were associated with decreased recruitment of inflammatory cells and reduced production of proinflammatory cytokines in cardiovascular organs. The demonstrated effects and immune-modulating mechanisms of DEL-1 in abrogation of cardiovascular remodeling and progression of hypertension identify DEL-1 as a potential therapeutic factor.

Objective, observer-independent evaluation of myocardial perfusion and function: role of SPECT.

The number of patients with coronary artery disease and ischaemic heart failure - and those with terminal heart failure - is increasing despite improvements in medical and interventional therapies of ischaemic heart disease - and, over the next decades, it is projected to continue to increase further. Observer-independent, reproducible imaging techniques play a fundamental role in objective evaluation of both conventional (such as surgical or percutaneous) myocardial revascularization and novel therapeutic approaches to reduce myocardial ischaemia, improve contractility and prevent adverse myocardial remodelling. To be applicable to clinical practice, the clinical study design and data should best be rooted in everyday clinical practice. Accurate and reproducible assessment of left ventricular ejection fraction, left ventricular volumes, myocardial perfusion and function is one of the most important objectives of cardiac imaging. Current techniques used both in clinical studies and in everyday clinical practice include 2- and 3-dimensional echocardiography, magnetic resonance imaging, single-photon emission computed tomography and positron emission tomography; each of these has its strengths and limitations. We review present evidence on the role of single-photon emission computed tomography as a technique that may offer, through being observer-independent, the most objective evaluation of evolution of left ventricular perfusion, volumes and ejection fraction.

Citrate-Saline-Formulated mRNA Delivery into the Heart Muscle with an Electromechanical Mapping and Injection Catheter Does Not Lead to Therapeutic Effects in a Porcine Chronic Myocardial Ischemia Model

Based on recent success in using modified RNA in clinical applications, we tested the safety, feasibility, and efficacy of direct delivery of citrate-saline-formulated mRNA into an hibernating ischemic heart muscle using an electromechanical mapping and injection catheter system (NOGA/Myostar) in a porcine chronic myocardial ischemia model. Chronic ischemia was induced in domestic pigs (n = 24) using a bottleneck stent placed in the left anterior descending coronary artery. Low (1 mg) and high (7.5 mg) doses of citrate-saline-formulated vascular endothelial growth factor (VEGF)-A165 mRNA were administered in the study. LacZ mRNA and citrate-saline buffer were used as controls. Ten intramyocardial injections (200 μL each) of the mRNAs or citrate-saline buffer were given endovascularly into the hibernating ischemic myocardium using the NOGA catheter. Positron emission tomography 15O-radiowater imaging was performed 7 days after the induction of ischemia and 28 days after the mRNA delivery to measure quantitative myocardial blood perfusion. Coronary angiography, left ventricular function measurements, and clinical chemistry were obtained at each time point. Thirty-five days after the mRNA transfers, pigs were sacrificed, and infarct size and general histology were analyzed. LacZ mRNA pigs were sacrificed 24 h after the transduction. Citrate-saline-formulated mRNA delivery into the ischemic myocardium with endovascular injection catheter did not lead to meaningful transduction with the translation of VEGF-A165, nor therapeutic effects in the heart. VEGF-A165 mRNA showed no statistically significant improvements in left ventricular ejection fraction (LVEF), cardiac output, myocardial perfusion, infarct size, collateral growth, or capillary area in the study groups. However, there was a trend in the high-dose group toward an improved LVEF and cardiac output at rest. No significant adverse effects were observed. In conclusion, the NOGA/Myostar injection catheter system is ineffective in delivering citrate-saline-formulated mRNAs into the heart muscle with the doses and methods used in a porcine chronic myocardial ischemia model.

Left ventricular myocardial cellular perfusion against the background of cardiac contractility modulation in patients with heart failure and atrial fibrillation

Aim. To assess the effect of cardiac contractility modulation (CCM) in patients with heart failure (HF) and atrial fibrillation (AF) on left ventricular (LV) myocardial cellular perfusion using perfusion single photon emission computed tomography (SPECT).Material and methods. 99mTc-MIBI SPECT gated myocardial perfusion imaging was performed in 60 patients with HF and AF before implantation of CCM device and after 6-months follow-up. All patients received long-term optimal medication therapy for HF. Results. The results obtained indicate a significant positive effect of CCM use in patients with HF and AF on LV ejection fraction (increase from 22 [18;30] to 25,5 [19;38] (p=0,002)), LV volume (decrease in LV end-systolic volume from 187 [114;238] to 154 [100;201] (p=0,001), end-diastolic volume from 229 [174;290] to 209 [159;259] (p=0,007)), as well as myocardial perfusion values. There is a favorable myocardial perfusion dynamics, which was more pronounced in nonischemic HF: increase in SRS from 6 [5;9] to 8,0 [6;11] after 6 months (p=0,01)). The extent of impaired perfusion significantly decreases from 12 [9;17] to 9 [6;16] (p=0,04). An indicator reflecting the total impairment of LV myocardial perfusion significantly decreases: total perfusion deficit decreased from 10 [8;14] to 7 [6;14] after 6 months (p=0,02), compared with ischemia-related HF.Conclusion. Perfusion SPECT makes it possible to assess the myocardial cellular perfusion during CCM therapy in patients with HF of various origin and AF. CCM therapy improves myocardial contractility and perfusion in patients with HF and AF.

Mechanical Dyssynchrony for Prediction of the Cardiac Resynchronization Therapy Response in Patients with Dilated Cardiomyopathy.

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 &lt;55 and a phase histogram steepness &gt;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.