Myocardial Viability Research Articles

Lesion Characterization by 99mTc-MIBI Myocardial Perfusion Imaging (MPI) & 18F-FDG Cardiac PET Following Myocardial Infarction Before Revascularization & Outcome Prediction: Initial Experience in Bangladesh

99mTc-MIBI SPECT myocardial perfusion imaging (MPI) and 18F-FDG cardiac positron emission tomography (Cardiac PET) can assess the extent and severity of myocardial perfusion and metabolic defect following myocardial infarction (MI) and also able to predict the outcome before revascularization in known coronary artery disease patients. About 135 cases of known coronary artery disease patients were enrolled here for combined nuclear imaging tests, rest only ECG gated MPI and FDG cardiac PET to assess myocardial perfusion and viability status following MI prior to revascularization. In this study we want to figure out the utility of this combined protocol for myocardial lesion characterization and its role for clinical decision-making in-patient selection prior to revascularization and treatment planning. We are also intended to share the initial outcome in available follow up cases. J Inv Clin Cardiol 2023; 5(2): 45-52

Non-invasive imaging to guide percutaneous coronary revascularization in chronic total occlusion: a systematic review and meta-analysis

Abstract Background and aims Whether recanalization of coronary chronic total occlusions (CTO) leads to improved patient outcomes is uncertain. We set out to investigate the use of noninvasive imaging modalities to guide patient selection for percutaneous recanalization of coronary chronic total occlusions (CTO-PCI) and its association with outcomes. Methods Systematic review and meta-analysis of studies involving patients undergoing CTO-PCI to detail use of preprocedural non-invasive imaging, change in clinical endpoints and the occurrence of clinical events in these patient cohorts. PubMed and Embase, the Cochrane Database of Systematic Reviews, the PROSPERO database and the Clinical Trials Registry were searched for relevant randomized and observational studies up to May 2023. This study is registered with PROSPERO. The study primary endpoint was a composite of all-cause death and nonfatal myocardial infarction (MI), with a secondary composite endpoint of cardiovascular death, nonfatal MI and target vessel revascularization (TVR). Additional endpoints were individual components of the composite endpoints along with changes in angina burden, LV ejection fraction, ischemic burden, and infarct extent after PCI. Results Of 1264 publications retrieved, 31 studies (26 observational and 5 randomized) were finally included for a total of 7260 patients. Guidance to CTO-PCI varied greatly among included studies, with only a minority implementing routine preprocedural inducible ischemia and myocardial viability assessment. At a median of 3.1 years (range 1-5 years), the primary endpoint occurred at a rate of 3.1 events per 100 patient-years (95%CI: 2.4-3.7). When non-invasive imaging was used to guide CTO-PCI, patients with myocardial ischemia and/or viability, a reduced risk for the primary endpoint was observed (OR 0.3 95%CI 0.2-0.5) compared to CTO-PCI without evidence of myocardial ischemia and/or viability. CTO-PCI was associated with improvements in SAQ summary score, LVEF, reduction of ischemic burden, improvement in myocardial perfusion (all P-values < 0.01), with no change in the burden of myocardial scarring. At meta-regression analysis, a greater improvement in LVEF was observed in studies enrolling patients with lower average baseline LVEF (≤ 45%) (R2 = 63%, p < 0.0001). Conclusions CTO-PCI led to a significant improvement in symptom status (reduction of chest pain) and LV ejection fraction. CTO-PCI guided by the presence of ischemia and/or viability was associated with improved patient outcomes compared with CTO-PCI in the absence of ischemia and/viability, or in patients where non-invasive imaging testing was not performed. Future randomized clinical trials testing whether ischemia and viability-guided CTO-PCI improves clinical outcomes are lacking and warranted.PRISMA Flow diagramGraphical abstract

Perfusion metabolism mismatch predicts short-term complications in Takotsubo syndrome

Abstract Background Takotsubo syndrome (TTS) is a transient cardiac condition triggered by sudden emotional or physical stress characterized by LV dysfunction in the absence of obstructive epicardial coronary artery disease. 123I-BMIPP, an iodinated fatty acid analogue, can identify impaired myocardial metabolic activity. With the use of dual SPECT protocol, reduced uptake of 123I-BMIPP compared to perfusion which is called perfusion-metabolic mismatch is observed in apical regions in TTS. The mismatch may indicate jeopardized but viable myocardium, reflecting transient ischemic damage or metabolically stunned myocardium. However, the association between the perfusion metabolism mismatch in TTS and its complications remains underexplored. Purpose Our study aimed to analyze the degree of perfusion metabolism mismatch at the acute phase in TTS and investigate its association with short-term complications. Methods This retrospective study conducted between 2012 and 2024 at a single center included 82 patients diagnosed with TTS. Patients underwent dual SPECT imaging using 99mTc or 201 Tl and 123I-BMIPP within two weeks of admission. We applied quantitative analysis using QGS/QPS software from Cedars-Sinai. Total perfusion deficit ("TPD") was calculated based on sex-matched normal limits providing the extent of perfusion abnormality. Meanwhile, perfusion-metabolism mismatch scores ("worsen") were determined by comparing the total BMIPP counts to the total counts of perfusion. We then assessed the correlation of these imaging findings with biomarkers, regional wall motion abnormalities, and the occurrence of short-term complications. Short-term complications included heart failure, left ventricular outflow (LVOT) obstruction, mitral regurgitation, cardiac arrhythmia, cardiogenic shock, left ventricle (LV) rupture, and cardiac death during the hospitalization period. Results All study patients exhibited wall motion abnormalities seen in apical segments. The count of myocardial segments with regional wall motion abnormality was correlated with both TPD (r=0.34, p=0.002) and perfusion metabolic mismatch score (r=0.40, p<0.001). TPD had a moderate correlation coefficient with max CK-MB (r=0.44, p<0.001) and troponin T (r=0.40, p<0.001) levels. However, perfusion metabolic mismatch did not display correlations with max CK-MB (r=0.05, p=0.65), and Troponin T (r=0.12, p=0.28) levels. Among 82 patients, 37 patients experienced any short-term complications. Importantly, patients with short-term complications had elevated perfusion mismatch scores compared to those without short-term complications (14.0 [6.0-22.5] vs. 5.0 [3.0-10.0], p<0.001). However, no significant difference was observed in TPD between the two groups (9.0 [4.5-20.0] vs. 7.0 [3.0-12.0], p=0.130). Conclusions Our research highlights a significant association between perfusion-metabolism mismatch and an increased risk for short-term complications in patients with Takotsubo syndrome.

Effect of primary pci in asymptomatic stemi patients presenting 12 to 48 hours of symptom onset, on myocardial viability assessed by spect tc 99m sestamibi scan epitome99

Abstract Background Guidelines on revascularization of asymptomatic stable STEMI patients presenting 12-48 hours of symptom onset are limited. We utilized TC-99mSestaMIBI scan to study the impact of primary PCI on myocardial viability by deriving myocardial salvage index (MSI) from area at risk (AAR), prior to revascularization and final infarct size (FIS) at follow up, in asymptomatic stable STEMI patients presenting between 12-48 hours of symptom onset to PCI. Purpose Evidence contributing lack of symptoms to a non-viable myocardium is lacking and it would be unethical to randomize patients with myocardial infarction (< 48 hours old) to a control arm or a non-intervention arm without evaluating the possibility of salvageable myocardium. Our study aims to inculcate evidence based management of late presenting stable asymptomatic STEMI patients. Methods We enrolled 141 patients presenting with STEMI (12-48 hours), from January 2021 to December 2023, who then underwent TC-99mSestaMIBI scan, followed by revascularization of IRA with 138 patients completing the designed study with follow-up scan at 3 months. Subjects were subcategorised into cohort A(12-24 hrs.), B(25-36 hrs.), and C(37-48 hrs.) according to the duration of symptom onset. Results A substantial MSI of > 0.50 was achieved by 36 %, 8% and 5 % of patients from cohort A, cohort B, and cohort C respectively. Although the AAR was comparable throughout cohorts, on post HOC analysis a statistically significant reduction in the final infarct size was seen among patients in cohort A vs C [Q = 4.72 (p = .00309)], while a reduction of FIS in cohort B and cohort C were obvious but statistically insignificant. Myocardial salvage index was smaller in late presenters, with no statistically significant difference among cohort B & cohort C [Q = 0.96 (p = .77697)]. Delaying the timing of Primary PCI from symptom onset was associated with larger AAR (R= - 0.01) & FIS (R= 0.35) although with a lower correlation coefficient. While evaluating MSI against timing of Primary PCI, a moderately negative (R= - 0.41) relation exists, indicating a linear correlation to reduced myocardial salvage Index with delay in the timing of primary PCI to symptom onset. Conclusion Asymptomatic stable STEMI patients presenting 12-24 hours of symptom onset to PCI, benefited from primary PCI with lesser final infarct size and larger MSI. Despite a comparable AAR across cohorts, MSI fell sharply among patients undergoing primary PCI 24-48 hours of symptom onset with a larger final infarct size, warranting viability guided revascularization. Although primary PCI improved final LVEF and MSI in patients with ischemic heart failure, parameter gain alone was insufficient in endeavoring a positive clinical impact.

The effect of Trimetazidine on the left ventricular global longitudinal strain assessed by cardiac magnetic resonance in stable angina patients with previous myocardial infarction and left ventricular

Abstract Introduction Trimetazidine (TMZ) is an anti-ischemic metabolic agent that is indicated in adults as add-on therapy for the symptomatic treatment of patients with stable angina pectoris (SA). Global left ventricular (LV) systolic function is an important predictor of outcomes in patients after myocardial infarction (MI). Cardiac magnetic resonance (CMR) imaging has now evolved into a major tool for the evaluation of patients with LV dysfunction, providing precise measurements of ejection fraction (EF) and viability assessment but also now allowing assessment of global longitudinal strain (GLS) from standard cine CMR images. We hypothesized that the use of TMZ 80 mg as an anti-ischemic agent in patients with SA, history of MI, reduced EF and in the presence of viable myocardium may produce an early modification of GLS. Methods TRIM-AZ - was a non-interventional, prospective Azerbaijan study to analyze the capacity of short-term therapy with TMZ 80 mg on LV GLS evaluated by CMR in patients with previous MI. Patients with a confirmed diagnosis of heart failure (HF) with impaired LV systolic function and SA in the presence of viable myocardium were included. The treatment of all patients was optimized according to the latest ESC guidelines before entry in the study. Patients were randomized into two groups, one received TMZ 80 mg on top of guidelines directed medical therapies, and the other was the control group. A CMR as well as a transthoracic echography were performed for all patients at the inclusion visit and 8 weeks later. Results 52 patients were included in the study, 30 patients in the TMZ group and 22 in the control group,. At baseline, the mean age was 62±7 years , 63% were smokers, 60% hypertensive, 60% diabetics, 48% had a family history of MI, 12% had typical symptoms of SA while 88% had atypical form (e.g. like shortness of breath). All patients received baseline therapy with ARNI/ACE-i, SGLT2 inhibitors, beta-blockers, MRA, ASA, and statin. 8 weeks after the initiation of TMZ, there were no significant changes in LVEF assessed both by Echo and CMR (29,8%±3,2% vs 30,1%±3,5% by echo in TMZ group; 31,3%±2,7% vs 31,6%±2,7% by echo in the control group; 25,9%±3,1% vs 26,9±4,1% by CMR in TMZ group; 26,9%±2,1% vs 30,1%±2,3% by CMR in the control group), however GLS was significantly improved in TMZ group (-9,9%±1,1% to -12,7%±1,2%, p=0,00), but not in control group (-9,3%±1,3% vs -10,3%±1,4% p=0,3). No adverse event related to TMZ use was reported during the study. Conclusion These findings suggest that the use of trimetazidine in patients with stable angina , previous MI and heart failure in the presence of viable myocardium could improve the left ventricular global longitudinal strain assessed by CMR.

Mechanisms leading to peri-procedural myocardial infarction in patients with focal versus diffuse coronary artery disease

Abstract Background PMI are characterized by an elevation in cardiac biomarkers, such as troponin, following PCI. Adherence to the 4th UDMIof PMI necessitates not only elevated cardiac biomarkers but also the presence of ECG changes, new loss of viable myocardium, or angiographic findings indicative of a procedural complication. Understanding the mechanisms underlying PMI and their associated factors is of paramount clinical significance. Our goal was to investigate the specific pathways contributing to the occurrence of PMI in stable patients undergoing PCI. Methods This prospective study was performed at 23 sites and enrolled patients with at least one epicardial lesion with an FFR≤0.80 planned to be treated by PCI. Each patient underwent a standardized physiological protocol, including manual FFR pullbacks with PPG calculation for the characterization of CAD patterns. The median PPG value (0.62) was used to divide patients into predominantly focal or diffuse disease. Troponin levels were measured after PCI, and patients exhibiting an elevation exceeding 5 times the upper limit of normal (ULN) were subject to evaluation by an independent clinical events committee. In addition, patients with large troponin elevation (>70 times above the ULN) were adjudicated as PMI as a standalone criterion. The primary objective was to investigate the mechanism leading to PMI in patients with focal versus diffuse CAD. Results Overall, 855 patients were included in this analysis, with 34.5% (295 patients) exhibiting a troponin elevation exceeding 5 times the ULN. Among these cases, 66 (7.7%) were adjudicated as PMI. The prevalence of secondary criteria for PMI was as follows: ECG changes at 7.6% (5/66), new loss of viable myocardium at 0%, side branch occlusion at 18.2% (12/66), and large troponin elevation at 84.8% (56/66). Diffuse disease (PPG < 0.62) was significantly associated with PMI (OR 1.71, 95% CI 1.03 to 2.88, p-value = 0.038). In the overall population, the occurrence of ECG changes after PCI was 0.7% in focal disease compared to 0.8% in diffuse disease (p-value=1.0). Side branch occlusion after PCI was observed in 0.7% in focal disease vs. 2.5% in diffuse disease (p-value=0.04), and large troponin elevation occurred in 4.8% in focal disease vs. 8.5% in diffuse disease (p-value=0.03). Additionally, PPG was significantly associated with the incidence of side branch occlusion (OR 1.71, 95% CI 1.03 to 2.88, p-value=0.038) and large troponin elevation after PCI (OR 1.83, 95% CI 1.06 to 3.22, p-value=0.038). Conclusion The presence of diffuse atherosclerosis, as defined by PPG, was linked to an increased risk of PMI. The mechanisms leading to PMI differed between patients with focal and diffuse disease. Patients with diffuse disease demonstrated a higher incidence of branch occlusion and large troponin elevation following PCI compared to those with focal CAD. Targeting patients with high PPG may improve outcomes after PCI.MACE by PPG

Prognostic value of additional midwall late gadolinium enhancement in patients with ischemic cardiomyopathy

Abstract Background Although several studies have reported the additional presence of midwall late gadolinium enhancement (LGE) using cardiac magnetic resonance (CMR) in patients with ischemic cardiomyopathy (ICM), its prognostic value is not well established. Purpose To assess the prognostic value of the additional presence of midwall-LGE in a large cohort of patients with ICM and reduced left ventricular ejection fraction (LVEF). Methods Between 2008 and 2022, all consecutive patients referred for myocardial viability assessment using CMR with an history of ICM (≥70% stenosis in ≥1 epicardial coronary vessel on angiography and/or history of myocardial infarction and/or coronary revascularization) and LVEF <50% were included. Midwall-LGE was defined by non-ischemic LGE corresponding to non-specific myocardial fibrosis. All patients with a history of acute myocarditis and/or sub-epicardial LGE were excluded. The primary outcome was all-cause death. Nested Cox proportional hazard models were used to assess the prognostic value of additional midwall-LGE including its location (lateral and/or septal and other location) and extent (1 or ≥2 segments), above the presence of ischemic-LGE and traditional prognostic factors. The incremental prognostic value of midwall-LGE extent and location was assessed by the C-statistic increment, the continuous net reclassification improvement (NRI), the integrative discrimination index (IDI) and the global Chi-2. Results Among the 6,082 included patients (65±12 years, 73% males), 702 (11.5%) had an additional midwall-LGE. During a median follow-up of 9 (IQR, 7-12) years, 652 (11%) patients died. The presence of midwall-LGE alone was strongly associated with the risk of death compared to patients without midwall-LGE (p<0.001, Figure 1A). Among these patients with midwall-LGE (N=702), survival curves showed an increased risk for midwall-LGE in lateral and/or septal location (p<0.001), for larger extent (p<0.001) and the presence of ischemic-LGE (p<0.001, Figure 1B). In this population with midwall-LGE (N=702), after adjustment for risk factors and extent of ischemic-LGE, midwall-LGE with septal and/or lateral location (adjusted HR: 2.6; 95%CI: 1.8-3.6) and extent ≥2 segments (adjusted HR: 2.6; 95%CI: 1.8-3.7, both p<0.001) were independently associated with all-cause death. A comprehensive LGE model combining all the characteristics of midwall-LGE showed the best improvement in model discrimination and reclassification above traditional prognosticators (C-statistic improvement: 0.13; NRI=46%; IDI=19%, Chi-2 global=261, all p<0.05; LR-test p<0.001, Figure 2). Conclusion In a large cohort of ICM patients, the presence of an additional non-ischemic midwall-LGE is an independent prognosticator of all-cause death, particularly for larger extent or when present in the septal and/or lateral location.Prognostic value of midwall-LGEIncremental prognostic value

Percutaneous revascularization in late-presenting STEMI with absence of viability: effects on left ventricular remodeling and scar

Abstract Introduction In patients with ST-elevation myocardial infarction (STEMI), percutaneous coronary intervention (PCI) should be conducted within 12 hours of symptom onset. The potential benefits attributable to late reperfusion in STEMI fall under the "open artery hypothesis" where the stunned peri-infarction zone after revascularization would restore blood supply and contractility. Purpose To estimate the differences on the LV ejection fraction (LVEF), indexed LV end-systolic volume (iLVESV) and scar in patients with STEMI without viabilitity randomized to optimal medical therapy (OMT) alone or OMT and a late percutaneous coronary intervention (PCI) performed between 24 hours and 30 days after the event. Methods Patients with non-reperfused STEMI were evaluated from September 2021 to June 2022 at a tertiary cardiology hospital. The patients underwent Cardiac Magnetic Resonance (CMR) to assess myocardial viability and were classified as non-viable if they had only 1 wall segment with less than fifty percent thickness of the affected wall with late gadolinium enhancement. The patients were randomized to PCI or OMT alone. CMR was repeated at 6 months to evaluate LVEF, iLVESV and fibrosis. This summary presents a planned partial analysis of the 6-month results (N=51). Descriptive statistics analysis included central and dispersion estimators, or absolute and relative frequencies. To explore the differences between groups and time, Mann-Whitney and Wilcoxon tests were run, and results were given as point-estimates and confidence intervals at 95% (95% CI). A significance level of 5% was adopted for inferential analysis. Results 51 patients (60±11 years, 71% male) were included in the analysis. Of this total, 24 were randomized to PCI + OMT, and 27 to isolated OMT. The groups showed balanced distribution regarding clinical characteristics and initial CMR parameters (LVEF, iLVESV, and fibrosis). The difference in LVEF at the end of 6 months between the OMT and PCI groups was 2.07%, favoring the OMT group; however, this difference was not significant (p= 0.677, 95% CI: -5 to 10). Between the groups, the difference at the end of 6 months in iLVESV was -6.82 ml/m², also without statistical significance (p= 0.858, 95% CI: -19 to 11). There was a significant reduction in the amount of fibrosis in both PCI group with -14.68g (p= 0.011) and in the OMT group with -12.57g (p= 0.009). Detailed results are presented in Table 1. Conclusion Despite a significant reduction in fibrosis in both groups, there was no superiority observed in late PCI compared to isolated OMT in reducing reverse remodeling and fibrosis in patients with non-viable STEMI when compared to isolated OMT.Remodeling changes.

Impact of CT attenuation correction on viable myocardium detection in combined SPECT and PET/CT: A retrospective cohort study.

The influence of computed tomography attenuation correction (CTAC) on the accuracy of diagnosing viable myocardium using Tc-99m-MIBI dedicated cardiac cadmium-zinc-telluride (CZT) single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) combined with F-18-FDG Positron Emission Tomography/Computed Tomography (PET/CT) metabolic imaging, compared with conventional SPECT MPI, remains to be fully elucidated. To evaluate the impact of CTAC on the accuracy of diagnosing viable myocardium using Tc-99m-MIBI dedicated cardiac CZT SPECT MPI combined with F-18-FDG PET/CT, compared to conventional SPECT MPI. 193 patients underwent CZT SPECT and F-18-FDG PET/CT imaging, while 39 patients underwent conventional SPECT and F-18-FDG PET/CT imaging, with both groups utilizing CT for attenuation correction. The injured myocardium (hibernating and scarring) was quantified using the Q.PET software. After CTAC, both groups showed significant improvements in perfusion of the injured myocardial areas, particularly in the inferior wall (INF). The reduction in perfusion was more notable in the CZT SPECT group than that in the conventional group, particularly in the inferior and lateral walls. Among patients with large cardiac chambers, those undergoing MPI with CZT, with normal weights, or males, hibernating myocardium (HM) and scar post-CTAC reductions were particularly significant in the INF. If HM ≥ 10% is considered an indicator for recommended revascularization, among the 87 patients without prior cardiac bypass, 25 (28.7%) might not require revascularization treatment. Dedicated cardiac CZT SPECT and conventional SPECT MPI combined with F-18-FDG PET/CT significantly influenced the assessment of viable myocardium. The impact of CTAC was more profound in dedicated cardiac CZT SPECT, particularly in the INF region. CTAC significantly enhances the accuracy of viable myocardial assessment and may influence clinical decisions regarding revascularization therapy. Therefore, CTAC should be routinely used in dedicated cardiac CZT SPECT MPI combined with F-18-FDG PET/CT for myocardial viability diagnosis.

A refined TTC assay precisely detects cardiac injury and cellular viability in the infarcted mouse heart

Histological analysis with 2,3,5-triphenyltetrazolium chloride (TTC) staining is the most frequently used tool to detect myocardial ischemia/reperfusion injury. However, its practicality is often challenged by poor image quality in gross histology, leading to an equivocal infarct-boundary delineation and potentially compromised measurement accuracy. Here, we introduce several crucial refinements in staining protocol and sample processing, which enable TTC images to be analyzed with light microscopy. The refined protocol involves a two-step TTC staining process (perfusion and immersion) and subsequent Zamboni fixation to differentiate myocardial viability and necrosis, and use of Coomassie brilliant blue to label area-at-risk. After the duo-staining steps were completed, the heart sample was embedded and sliced transversally by a cryostat into a series of thin sections (50 µm) for microscopic analysis. The refined TTC (redTTC) assay yielded remarkably high-quality images with striking color intensity and sharply defined boundaries, permitting unambiguous and reliable delineation of the infarct and area-at-risk. In the same animals, the redTTC assay showed good agreement with the in-vivo gold standard measurements (LGE and MEMRI). Meanwhile, redTTC imaging allows tracking of viable cardiomyocytes at cellular resolution, and with this enhanced capability, we convincingly demonstrated the pro-survival action of stem cells based-therapy. Therefore, the redTTC assay represents a significant technical advance that permits precise detection of the true extent of cardiac injury and cardiomyocyte viability. This approach is cost-effective and may be adapted for use in diverse applications, making it highly appealing to many laboratories performing ischemia/reperfusion injury experiments.

Feasibility of shortening scan duration of 18F-FDG myocardial metabolism imaging using a total-body PET/CT scanner

PurposeTo evaluate 18F-FDG myocardial metabolism imaging (MMI) using a total-body PET/CT scanner and explore the feasible scan duration to guide the clinical practice.MethodsA retrospective analysis was conducted on 41 patients who underwent myocardial perfusion-metabolism imaging to assess myocardial viability. The patients underwent 18F-FDG MMI with a total-body PET/CT scanner using a list-mode for 600 s. PET data were trimmed and reconstructed to simulate images of 600-s, 300-s, 120-s, 60-s, and 30-s acquisition time (G600-G30). Images among different groups were subjectively evaluated using a 5-point Likert scale. Semi-quantitative evaluation was performed using standardized uptake value (SUV), myocardial to background activity ratio (M/B), signal to noise ratio (SNR), contrast to noise ratio (CNR), contrast ratio (CR), and coefficient of variation (CV). Myocardial viability analysis included indexes of Mismatch and Scar. G600 served as the reference.ResultsSubjective visual evaluation indicated a decline in the scores of image quality with shortening scan duration. All the G600, G300, and G120 images were clinically acceptable (score ≥ 3), and their image quality scores were 4.9 ± 0.3, 4.8 ± 0.4, and 4.5 ± 0.8, respectively (P > 0.05). Moreover, as the scan duration reduced, the semi-quantitative parameters M/B, SNR, CNR, and CR decreased, while SUV and CV increased, and significant difference was observed in G300-G30 groups when comparing to G600 group (P < 0.05). For myocardial viability analysis of left ventricular and coronary segments, the Mismatch and Scar values of G300-G30 groups were almost identical to G600 group (ICC: 0.968-1.0, P < 0.001).ConclusionSufficient image quality for clinical diagnosis could be achieved at G120 for MMI using a total-body PET/CT scanner, while the image quality of G30 was acceptable for myocardial viability analysis.

A Feasibility Study of [18F]F-AraG Positron Emission Tomography (PET) for Cardiac Imaging-Myocardial Viability in Ischemia-Reperfusion Injury Model.

Myocardial infarction (MI) with subsequent inflammation is one of the most common heart conditions leading to progressive tissue damage. A reliable imaging marker to assess tissue viability after MI would help determine the risks and benefits of any intervention. In this study, we investigate whether a new mitochondria-targeted imaging agent, 18F-labeled 2'-deoxy-2'-18F-fluoro-9-β-d-arabinofuranosylguanine ([18F]F-AraG), a positron emission tomography (PET) agent developed for imaging activated T cells, is suitable for cardiac imaging and to test the myocardial viability after MI. To test whether the myocardial [18F]-F-AraG signal is coming from cardiomyocytes or immune infiltrates, we compared cardiac signal in wild-type (WT) mice with that of T cell deficient Rag1 knockout (Rag1 KO) mice. We assessed the effect of dietary nucleotides on myocardial [18F]F-AraG uptake in normal heart by comparing [18F]F-AraG signals between mice fed with purified diet and those fed with purified diet supplemented with nucleotides. The myocardial viability was investigated in rodent model by imaging rat with [18F]F-AraG and 2-deoxy-2[18F]fluoro-D-glucose ([18F]FDG) before and after MI. All PET signals were quantified in terms of the percent injected dose per cc (%ID/cc). We also explored [18F]FDG signal variability and potential T cell infiltration into fibrotic area in the affected myocardium with H&E analysis. The difference in %ID/cc for Rag1 KO and WT mice was not significant (p = ns) indicating that the [18F]F-AraG signal in the myocardium was primarily coming from cardiomyocytes. No difference in myocardial uptake was observed between [18F]F-AraG signals in mice fed with purified diet and with purified diet supplemented with nucleotides (p = ns). The [18F]FDG signals showed wider variability at different time points. Noticeable [18F]F-AraG signals were observed in the affected MI regions. There were T cells in the fibrotic area in the H&E analysis, but they did not constitute the predominant infiltrates. Our preliminary preclinical data show that [18F]F-AraG accumulates in cardiomyocytes indicating that it may be suitable for cardiac imaging and to evaluate the myocardial viability after MI.

Cardioprotective Action of the JNK Inhibitor Tryptanthrin Oxime in the Late Period after Myocardial Infarction.

In experiments on Wistar rats, the effect of a new selective JNK inhibitor tryptanthrin oxime (TR-Ox) on parameters of systemic hemodynamics, cardiohemodynamics, and post-infarction fibrosis was studied 4 months after acute myocardial ischemia (1 h) followed by reperfusion. TR-Ox was administered intraperitoneally at a dose of 12 mg/kg 20 min before reperfusion, and then once a day for the next 4 days. Administration of TR-Ox to animals in the acute phase of myocardial infarction contributed to more complete preservation of myocardial viability in the delayed period: a relative increase of muscle elements proportion in the scar, a decrease in the formation of connective tissue areas with complete and >50% replacement of the myocardium, and deceleration of fibrotic scarring in myocardium areas distant from the focus of injury, resulting in improved systolic and diastolic myocardial function. Four months after myocardial infarction, significant improvement in systemic hemodynamics and cardiohemodynamics parameters was observed in the group treated with TR-Ox: stroke volume, cardiac output, left ventricular systolic pressure, maximum rates of left ventricle pressure rise and fall significantly increased and the left ventricle end-diastolic pressure decreased in comparison with the corresponding parameters in the control group.

A Methodology to Measure Glucose Metabolism by Quantitative Analysis of PET Images.

Positron emission tomography (PET) with F-18 fluorodeoxyglucose (FDG) tracer is the standard clinical technique to measure myocardial and vessel metabolism and viability and to investigate the metabolic syndrome associated with cardiovascular diseases. The quantitative analysis of PET images allows one to study the cardiovascular physiological processes, by extracting quantitative parameters from the analysis of the tracer kinetic. Here, we propose a new methodology to quantify and evaluate the evolution of glucose metabolism inside the myocardium and the large vascular structures over time. We merge and analyze PET and CT cardiac images, extracting different volumes of interest (VOI) and performing quantitative measurements. To validate it, we apply the methodology to merge images of the aorta vessel for patients affected by metabolic syndrome. The application of the proposed approach to the use case reveals a correlation between administered drugs and metabolic syndrome, measuring the glucose metabolic rate (MRGlu) in both the myocardium and aorta. The proposed methodology can be used to evaluate some cardiovascular risk indexes of diabetic patients, too. The proposed methodology can also be deployed to analyze other application domains.

The Role of Coronary Imaging in Chronic Total Occlusions: Applications and Future Possibilities.

Chronic total occlusions (CTOs) represent a challenging scenario in coronary artery disease (CAD). The prevalence of CTOS in patients undergoing coronary angiography underscores the need for effective diagnostic and therapeutic strategies. Coronary angiography, while essential, offers limited insights into lesion morphology, vessel course, and myocardial viability. In contrast, coronary imaging techniques-including optical coherence tomography (OCT), intravascular ultrasound (IVUS), and coronary computed tomography angiography (CCTA)-provide comprehensive insights for each stage of CTO percutaneous coronary intervention (PCI). OCT facilitates the assessment of plaque morphology and stent optimization, despite low evidence and several limitations in CTO-PCI. IVUS offers deeper penetration, allowing managing proximal cap scenarios and guiding subintimal navigation. CCTA provides a non-invasive, three-dimensional view of coronary anatomy, enabling the precise evaluation of myocardial mass at risk and detailed procedural planning. Despite their individual limitations, these imaging modalities have enhanced the success rates of CTO-PCI, thus reducing procedural and long-term complications and improving patient outcomes. The future of CTO management lies in further technological advancements, including hybrid imaging, artificial intelligence (AI) integration, and improved fusion imaging. These innovations promise to refine procedural precision and personalize interventions, ultimately improving the care of patients with complex coronary artery disease.

A Novel Approach to Identifying Hibernating Myocardium Using Radiomics-Based Machine Learning.

Background To assess the feasibility of a machine learning (ML) approach using radiomics features of perfusion defects on rest myocardial perfusion imaging (MPI) to detect the presence of hibernating myocardium. Methodology Data of patients who underwent 99mTc-sestamibi MPI and 18F-FDG PET/CT for myocardial viability assessment were retrieved. Rest MPI data were processed on ECToolbox, and polar maps were saved using theNFile PMap tool. The reference standard for defining hibernating myocardium was the presence of mismatched perfusion-metabolism defect with impaired myocardial contractility at rest. Perfusion defects on the polar maps were delineated with regions of interest (ROIs) after spatial resampling and intensity discretization. Replicable random sampling allocated 80% (257) of the perfusion defects of the patients from January 2017 to September 2022 to the training set and the remaining 20% (64) to the validation set. An independent dataset of perfusion defects from 29 consecutive patients from October 2022 to January 2023 was used as the testing set for model evaluation. One hundred ten first and second-order texture features were extracted for each ROI. After feature normalization and imputation, 14 best-ranked features were selected using a multistep feature selection process including the Logistic Regression and Fast Correlation-Based Filter. Thirteen supervised ML algorithms were trained with stratified five-fold cross-validation on the training set and validated on the validation set. The ML algorithms with a Log Loss of <0.688 and <0.672 in the cross-validation and validation steps were evaluated on the testing set. Performance matrices of the algorithms assessed included area under the curve (AUC), classification accuracy (CA), F1 score, precision, recall, and specificity. To provide transparency and interpretability, SHapley Additive exPlanations (SHAP) values were assessed and depicted as beeswarm plots. Results Two hundred thirty-nine patients (214 males; mean age 56 ± 11 years) were enrolled in the study. There were 371 perfusion defects (321 in the training and validation sets; 50 in the testing set). Based on the reference standard, 168 perfusion defects had hibernating myocardium (139 in the training and validation sets; 29 in the testing set). On cross-validation, six ML algorithms with Log Loss <0.688 had AUC >0.800. On validation, 10 ML algorithms had a Log Loss value <0.672, among which six had AUC >0.800. On model evaluation of the selected models on the unseen testing set, nine ML models had AUC >0.800 with Gradient Boosting Random Forest (xgboost) [GB RF (xgboost)] achieving the highest AUC of 0.860 and could detect the presence of hibernating myocardium in 21/29 (72.4%) perfusion defects with a precision of 87.5% (21/24), specificity 85.7% (18/21), CA 78.0% (39/50) and F1 Score 0.792. Four models depicted a clear pattern of model interpretability based on the beeswarm SHAP plots. These were GB RF (xgboost), GB (scikit-learn), GB (xgboost), and Random Forest. Conclusion Our study demonstrates the potential of ML in detecting hibernating myocardium using radiomics features extracted from perfusion defects on rest MPI images. This proof-of-concept underscores the notion that radiomics features capture nuanced information beyond what is perceptible to the human eye, offering promising avenues for improved myocardial viability assessment.

Image Quality of Cardiac Silicon Photomultiplier PET/CT Using an Infant Phantom of Extremely Low Birth Weight.

The lack of pediatrics-specific equipment for nuclear medicine imaging has resulted in insufficient diagnostic information for newborns, especially low-birth-weight infants. Although PET offers high spatial resolution and low radiation exposure, its use in newborns is limited. This study investigated the feasibility of cardiac PET imaging using the latest silicon photomultiplier (SiPM) PET technology in infants of extremely low birth weight (ELBW) using a phantom model. Methods: The study used a phantom model representing a 500-g ELBW infant with brain, cardiac, liver, and lung tissues. The cardiac tissue included a 3-mm-thick defect mimicking myocardial infarction. Organ tracer concentrations were calculated assuming 18F-FDG myocardial viability scans and 18F-flurpiridaz myocardial perfusion scans and were added to the phantom organs. Imaging was performed using an SiPM PET/CT scanner with a 5-min acquisition. The data acquired in list mode were reconstructed using 3-dimensional ordered-subsets expectation maximization with varying iterations. Image evaluation was based on the depiction of the myocardial defect compared with normal myocardial accumulation. Results: Increasing the number of iterations improved the contrast of the myocardial defect for both tracers, with 18F-flurpiridaz showing higher contrast than 18F-FDG. However, even at 50 iterations, both tracers overestimated the defect accumulation. A bull's-eye image can display the flow metabolism mismatch using images from both tracers. Conclusion: SiPM PET enabled cardiac PET imaging in a 500-g ELBW phantom with a 1-g heart. However, there were limitations in adequately depicting these defects. Considering the image quality and defect contrast,18F-flurpiridaz appears more desirable than 18F-FDG if only one of the two can be used.

Current and Future Roles of Glycoprotein IIb-IIIa Inhibitors in Primary Angioplasty for ST-Segment Elevation Myocardial Infarction.

Acute myocardial infarction still represents the major cause of mortality in high-income countries. Therefore, considerable efforts have been focused on the treatment of myocardial infarctions in the acute and long-term phase, with special attention being paid to reperfusion strategies and adjunctive antithrombotic therapies. In fact, despite the successful mechanical recanalization of the epicardial conduit, a substantial percentage of patients still experience poor myocardial reperfusion or acute/subacute in-stent thrombosis. Due the delayed onset of action of currently available oral antiplatelet therapies, glycoprotein (GP) IIb-IIIa inhibitors could be expected to improve clinical outcomes, especially when administrated in the early phase of the infarction, due to the larger platelet composition of fresh thrombi, the dynamic nature of early thrombi, and the larger amount of viable myocardium existing in the early, as compared to a delayed, phase. Considerable evidence has accumulated regarding the benefits from GP IIb-IIIa inhibitors on mortality, especially among high-risk patients and when administered as an upstream strategy. Therefore, based on currently available data, GP IIb-IIIa inhibitors can be considered when the drug can be administered within the first 3 h of symptom onset and among high-risk patients (e.g., those with advanced Killip class or an anterior myocardial infarction). Even though it is not universally accepted, in our opinion, this strategy should be implemented in a pre-hospital setting (in an ambulance) or as soon as possible when arriving at the hospital (at the Emergency Room or Coronary Care Unit, irrespective of whether they are in spoke or hub hospitals). A new, second-generation GP IIb-IIIa inhibitor (zalunfiban) appears to be highly suitable as a pre-hospital pharmacological facilitation strategy at the time of first medical contact due to its favourable features, including its simple subcutaneous administration, rapid onset of action (15 min), and limited time of action (with a half-life of ~1 h), which is likely to minimize the risk of bleeding. The ongoing CELEBRATE trial, including 2499 STEMI patients, may potentially provide compelling data to support the upstream treatment of STEMI patients undergoing mechanical reperfusion. In fact, although the current therapeutic target of increased rates of timely reperfusion has been achieved, the future goal in myocardial infarction treatment should be to achieve the most rapid reperfusion prior to primary percutaneous coronary intervention, thus further minimizing myocardial damage, or, in some cases, even preventing it completely, and improving survival.

Whole-Heart Histological and Electroanatomic Assessment of Postinfarction Cardiac Magnetic Resonance Imaging Scar and Conducting Channels.

Cardiac magnetic resonance imaging (CMR)-defined ventricular scar and anatomic conduction channels (CMR-CCs) offer promise in delineating ventricular tachycardia substrate. No studies have validated channels with coregistered histology, nor have they ascertained the histological characteristics of deceleration zones (DZs) within these channels. We aimed to validate CMR scar and CMR-CCs with whole-heart histology and electroanatomic mapping in a postinfarction model. Five sheep underwent anteroseptal infarction. CMR (116±20 days post infarct) was postprocessed using ADAS-3D, varying pixel intensity thresholds (5545, 6040, 6535, and 7030). DZs were identified by electroanatomic mapping (129±12 days post infarct). Explanted hearts were sectioned and stained with Picrosirius red, and whole-heart histopathologic shells were generated. Scar topography as well as percentage fibrosis, adiposity, and remaining viable myocardium within 3 mm histological biopsies and within CMR-CCs were determined. Using the standard 6040 thresholding, CMR had 83.8% accuracy for identifying histological scar in the endocardium (κ, 0.666) and 61.4% in the epicardium (κ, 0.276). Thirty-seven CMR-CCs were identified by varying thresholding; 23 (62%) were unique. DZs colocalized to 19 of 23 (83%) CMR-CCs. Twenty (87%) CMR-CCs were histologically confirmed. Within-channel histological fibrosis did not differ by the presence of DZs (P=0.242). Within-channel histological adiposity was significantly higher at sites with versus without DZs (24.1% versus 8.3%; P<0.001). Postprocessed CMR-derived scars and channels were validated by histology and electroanatomic mapping. Regions of CMR-CCs at sites of DZs had higher adiposity but similar fibrosis than regions without DZs, suggesting that lipomatous metaplasia may contribute to arrhythmogenicity of postinfarction scar.

Snhg14/miR-181a-5p axis-mediated “M1” macrophages aggravate LPS-induced myocardial cell injury

An increasing number of studies have suggested that macrophages participate in sepsis-induced myocardial injury. Our study highlights the function and mechanism of the lncRNA Snhg14 in “M1” polarized macrophage-mediated myocardial cell damage. Lipopolysaccharide (LPS) was used to treat H9c2 cells to construct an in vitro myocardial injury model. M1 and M2 polarization of RAW264.7 cells were induced and the exosomes were obtained from the supernatant through ultracentrifugation. Moreover, cecal ligation and puncture (CLP) surgery was implemented to establish a mouse sepsis-induced myocardial injury model, and Snhg14 was knocked down with sh-Snhg14. The results showed that the conditioned medium (CM) and the exosomes (Exo) of M1 macrophages substantially augmented LPS-induced apoptosis and oxidative stress in myocardial cells. Notably, M1-CM and M1-Exo contributed to nearly 50 % of myocardial cell viability decline. Snhg14 was highly expressed in M1 macrophages and exosomes derived from M1-MΦ (M1-Exo). Snhg14 overexpression aggravated myocardial cell damage and increased 10 to 50 times expression of proinflammatory cytokines in MΦ. Snhg14 knockdown reversed M1-Exo-mediated myocardial cell damage and inhibited the production of proinflammatory cytokines (50 %–75 % decline) of MΦ. Moreover, Snhg14 targeted and inhibited miR-181a-5p expression. miR-181a-5p upregulation partly reversed Snhg4 overexpression-mediated myocardial cell damage and MΦ activation. In vivo, sh-Snhg14 dramatically ameliorated cardiac damage in septic mice by enhancing miR-181a-5p and inhibiting the HMGB1/NF-κB pathway. In conclusion, “M1” macrophage-derived exosomal Snhg14 aggravates myocardial cell damage by modulating the miR-181a-5p/HMGB1/NF-κB pathway.