Feasibility and Diagnostic Performance of Functional SYNTAX Score Derived From Dynamic CT Myocardial Perfusion Imaging.

BACKGROUND: Computed tomography (CT) fractional flow reserve (FFR)-derived functional SYNTAX score (FSSCT-FFR) is a valuable method for guiding treatment strategy in patients with multivessel coronary artery disease. Dynamic CT myocardial perfusion imaging (CT-MPI) demonstrates higher diagnostic accuracy than CT-FFR in identifying hemodynamically significant coronary artery disease. We aimed to evaluate the feasibility of CT-MPI-derived FSS (FSSCT-MPI) with reference to invasive FSS. METHODS: In this retrospective study, patients with multivessel coronary artery disease who underwent dynamic CT-MPI+ coronary CT angiography and invasive coronary angiography or FFR within 4 weeks were consecutively included. Invasive (FSSinvasive) and noninvasive FSS (FSSCT-MPI and FSSCT-FFR) were calculated by an online calculator, which assigned points to lesions with hemodynamic significance (defined as FFRinvasive ≤0.80, invasive coronary angiography diameter stenosis ≥90%, CT-FFR ≤0.80, and myocardial ischemia on CT-MPI). Weighted κ value and net reclassification index were calculated to determine the consistency and incremental discriminatory power of FSSCT-MPI. Receiver operating characteristic curve analysis was used for the comparison of FSSCT-MPI and FSSCT-FFR in detecting intermediate- to high-risk patients. RESULTS: A total of 119 patients (96 men; 64.6±10.6 years) with 305 obstructive lesions were included. The average FSSCT-MPI, FSSCT-FFR, and FSSinvasive were 15.58±13.03, 16.18±13.30, and 13.11±12.22, respectively. The agreement on risk classification based on the FSSCT-MPI tertiles was good (weighted κ, 0.808). With reference to FSSinvasive, FSSCT-MPI correctly reclassified 27 (22.7%) patients from the intermediate- to high SYNTAX score group to the low-score group (net reclassification index, 0.30; P<0.001). In patients with severe calcification, FSSCT-MPI had better diagnostic value than FSSCT-FFR in detecting intermediate- to high-risk patients when compared with FSSinvasive (area under the curve, 0.976 versus 0.884; P<0.001). CONCLUSIONS: Noninvasive FSS derived from CT-MPI is feasible and has strong concordance with FSSinvasive. It allows accurate categorization of FSS in patients with multivessel coronary artery disease, in particular with severe calcification.

Papel del radiofarmacéutico clínico en la seguridad del paciente durante los estudios de perfusión miocárdica de esfuerzo con vasodilatadores / Role of the clinical radiopharmacist in patient safety during myocardial perfusion imaging with vasodilator stress agents

Objetivos: Evaluar el papel del radiofarmacéutico en un equipo multidisciplinar en la detección de contraindicaciones del regadenosón para su uso seguro en pacientes a los que se solicitó una SPECT de perfusión miocárdica. Métodos: Se estudió ambispectivamente su uso seguro en 1.905 pacientes (54,1% mujeres, edad media: 66,6±11,7 años, rango: 20-95años). Se registraron datos relativos al sexo, a la edad, al historial médico, a la medicación, a las alergias medicamentosas y a las contraindicaciones para el estrés farmacológico, así como las recomendaciones realizadas al médico nuclear responsable. Resultados: Las contraindicaciones detectadas y las correspondientes recomendaciones fueron las siguientes: riesgo de prolongación del intervalo QTc (7,5%): comprobación previa del intervalo QTc y monitorización del ECG; ictus o AIT previo (4,2%): evaluación de estenosis carotídea; alergia a salicilatos y/o sulfamidas (3,1%): empleo de [99mTc]Tc-MIBI; epilepsia o riesgo de convulsiones (2,4%): uso de adenosina o reconsiderar su indicación; tratamiento con corticosteroides sistémicos en EPOC severa (1,3%): reevaluar las condiciones del paciente; EPOC reagudizada (0,8%): posponer hasta la resolución del episodio agudo; asma grave (0,4%): no realizar la prueba; toma de metilxantinas (0,3%): evitar su consumo previo; otras (6,1%): evaluación de cada contraindicación. No se observaron contraindicaciones en el 73,6% de los pacientes. Se anularon el 2,9% de las peticiones debido a contraindicaciones absolutas. Conclusiones: Empleando una metodología de trabajo sistemática, el radiofarmacéutico detectó un elevado número de incidencias, presentando uno de cada cuatro pacientes alguna contraindicación clínica. Las recomendaciones emitidas fueron aceptadas por los médicos nucleares, que modificaron su enfoque, incrementando así la seguridad de estos pacientes.(AU)

Aim: To assess the radiopharmacist's role in a multidisciplinary team focused on the contraindications of regadenoson in order to ensure the safe use of pharmacologic vasodilator stress agents in patients undergoing SPECT-MPI. Methods: We ambispectively studied its safe use in 1905 patients (54.1% female, mean age: 66.6±11.7 years, range: 20-95years). Sex, age, medical history, medications, drug allergies, and contraindications for stress testing were registered together with recommendations for the nuclear physician in charge. Results: Detected contraindications and corresponding recommendations were as follows: risk factors for QTc interval prolongation 7.5% — measurement of QTc interval previously to test and monitor ECG; prior stroke or TIA 4.2% — consider carotid stenosis assessment; salicylates/sulfonamides allergy 3.1% — use 99mTc-sestamibi; epilepsy or risk factors for seizures 2.4% — use of adenosine or reconsider test indication; systemic corticosteroid therapy for severe COPD 1.3% — reassessment of patient's condition; acute exacerbation of COPD 0.8% — defer test until acute episode is over; severe asthma 0.4% — do not perform test; methylxanthine ingestion 0.3% — avoid consumption previously; other 6.1% — evaluation of other contraindications. No contraindications were detected in 73.6% of patients. The test was cancelled due to absolute contraindications in 2.9% of the requests. Conclusions: Working in a systematic way, the radiopharmacist was able to detect a high number of issues related to regadenoson, with one out of four patients presenting some clinical contraindication. The recommendations given by the radiopharmacist were well accepted by the nuclear physicians who changed their approach contributing to increase the safety of patients referred for MPI.(AU)

Improvement in the estimation of perfusable tissue fraction and myocardial flow reserve in the ischemic myocardial lesions using ECG-gated dynamic myocardial PET with 15O-water.

OBJECTIVE: Perfusable tissue fraction (PTF) and myocardial flow reserve (MFR) from 15O-water dynamic positron emission tomography (PET) are parameters of myocardial viability. However, myocardial motion causes errors in these values. We aimed to develop accurate estimation of PTF and MFR in ischemic lesions using an electro-cardiogram (ECG)-gated dynamic myocardial PET with 15O-water. METHODS: Twenty-seven patients with ischemic heart disease were enrolled. All patients underwent percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). List mode 3D PET data and ECG signals were acquired using Philips Gemini TF64 instrument. For each scan, 500 MBq of 15O-water was infused slowly for 2 min, and the dynamic data were scanned for 6 min. Both non-gated dynamic images and ECG-gated diastolic dynamic images were reconstructed. On the myocardial PET images of each patient, the entire myocardial region of interest (ROI) was set and divided into 17 segments. Myocardial blood flow in the resting state (rest MBF), hyperemic state (stress MBF), PTF, and MFR in each segment were estimated from both non-gated and ECG-gated dynamic PET images. Coronary arteriograms were obtained for all patients. In total, 128 normal segments without stenosis and 50 ischemic segments with > 90% stenosis were evaluated. RESULTS: In the ischemic myocardial segments, the PTF with ECG-gated PET was estimated as significantly lower than that with non-gated PET (0.63 ± 0.09 vs. 0.72 ± 0.08 [mL/mL], p < 0.001). The ECG-gated PET estimated a significantly lower PTF in the ischemic segments than in the normal segments (0.63 ± 0.09 vs. 0.67 ± 0.07 [mL/mL], p < 0.01). In the normal segments, the ECG-gated PET detected no significant difference in MFR compared with those from the non-gated PET (2.15 ± 0.76 vs. 2.24 ± 0.79, p = 0.28). However, in the ischemic myocardial segments, the MFR with ECG-gated PET was estimated as significantly lower than that with the non-gated PET (1.23 ± 0.29 vs. 1.69 ± 0.71, p < 0.001). The ECG-gated PET presented a significantly higher inter-observer reproducibility of PTF and rest MBF than the non-gated PET (p < 0.01). Neither stress MBF nor MFR yielded significant differences in inter-observer reproducibility between the ECG-gated and non-gated PET. CONCLUSIONS: The ECG-gated dynamic 15O-water PET suppressed the myocardial motion effect and resulted in a lower PTF and MFR in ischemic myocardial lesions than the non-gated PET. The ECG-gated PET seemed to be better than the conventional non-gated dynamic PET for the detection of ischemic myocardial lesion.

Feasibility of myocardial blood flow quantification to detect flow-limited coronary artery disease with a one-day rest/stress continuous rapid imaging protocol on cardiac-dedicated cadmium zinc telluride single photon emission computed tomography.

BACKGROUND: It is clinically needed to explore a more efficient imaging protocol for single photon emission computed tomography (SPECT) myocardial blood flow (MBF) quantitation derived from cadmium zinc telluride (CZT) SPECT camera for the routine clinical utilization. METHODS: One hundred and twenty patients with matched clinical characteristics and angiographic findings who completed one-day rest/stress SPECT imaging with either the intermittently sequential imaging (ISI) protocol (two dynamic and two electrocardiography (ECG)-gated scans) or the continuous rapid imaging (CRI) protocol (two dynamic/ECG-gated scans) were included. MBF quantitation adopted residual activity correction (RAC) to correct for rest residual activity (RRA) in the stress dynamic SPECT scan for the detection of flow-limited coronary artery disease. RESULTS: The CRI protocol reduced about 6.2 times shorter than the ISI protocol (25.5 min vs 157.6 min), but slightly higher than the RRA (26.7% ± 3.6% vs 22.3% ± 4.9%). With RAC, both protocols demonstrated close stress MBF (2.18 ± 1.13 vs 2.05 ± 1.10, P > 0.05) and myocardial flow reserve (MFR) (2.42 ± 1.05 vs 2.48 ± 1.11, P > 0.05) to deliver comparable diagnostic performance (sensitivity = 82.1%-92.3%, specificity = 81.2%-91.2%). Myocardial perfusion and left ventricular function overall showed no significant difference (all P > 0.26). CONCLUSION: One-day rest/stress SPECT with the CRI protocol and rest RAC is feasible to warrant the diagnostic performance of MBF quantitation with a shortened examination time and enhanced patient comfort. Further evaluation on the impact of extracardiac activity to regional MBF and perfusion pattern is required. Additional evaluation is needed in a patient population that is typical of those referred for SPECT MPI, including those with known or suspected coronary microvascular disease.

Gammagrafía de perfusión miocárdica en la evaluación del riesgo cardiovascular en el trasplante hepático de adultos / Myocardial perfusion scintigraphy in the assessment of cardiovascular risk in adult liver transplantation

Introducción El estudio diagnóstico no invasivo del riesgo cardiovascular en pacientes que van a ser llevados a trasplante hepático no es claro especialmente en asintomáticos. Respecto a la gammagrafía de perfusión miocárdica (GPM) se ha pensado que la reserva vasodilatadora deteriorada en estos pacientes puede reducir su rendimiento. El objetivo es valorar el papel de la GPM en la evaluación prequirúrgica de los pacientes que van a ser tratados mediante un trasplante hepático. Material y métodos Estudio retrospectivo, descriptivo y observacional. Se incluyó a todos los pacientes adultos llevados a trasplante hepático entre 2017 y 2021 que tuvieran GPM previa. Se describen los hallazgos de la GPM y se correlacionaron con los hallazgos de angiografía invasiva y con la aparición o no de eventos cardiovasculares peri y postrasplante. Resultados De 188 pacientes trasplantados (edad promedio: 57 años, DE: 12), 178 tenían perfusión miocárdica previa, 82 (46%) pacientes no tenían factores de riesgo cardiovascular y 5 (2,8%) tenían antecedente de enfermedad coronaria. De las GPM, 177 fueron con estrés con dipiridamol realizadas en promedio 10 meses antes del trasplante. Únicamente 17/178 (9,5%) estudios fueron anormales. El seguimiento medio fue de 38 meses (DE: 10). De los pacientes con GPM normal, solo 2 (1,2%) presentaron eventos cardiovasculares, ambos con estudios realizados más de 2años atrás. No hubo muertes de origen cardiovascular. Conclusiones La GPM es una técnica segura y confiable en la valoración cardiovascular en pacientes candidatos a trasplante hepático dada la baja tasa de falsos negativos en el seguimiento (AU)

Introduction The non-invasive diagnostic study of cardiovascular risk in patients who are going to undergo liver transplantation is not clear, especially in asymptomatic patients. Regarding myocardial perfusion scintigraphy (MPS), it has been thought that the impaired vasodilator reserve in these patients may reduce its performance. The objective is to assess the role of the MPS in the pre-surgical evaluation of patients who are going to undergo liver transplantation. Material and methods Retrospective, descriptive and observational study was designed. All adult patients undergoing liver transplantation between 2017 and 2021 who had previous MPS were included. The findings of MPS were described and correlated with the findings of invasive angiography and with the appearance or not of peri- and post-transplant cardiovascular events. Results There were a total of 188 transplanted patients (mean age: 57 years, SD: 12), 178 had previous myocardial perfusion, 82 (46%) patients had no cardiovascular risk factors, and 5 (2.8%) had a history of coronary disease. Of the MPS, 177 were with dipyridamole stress performed on average 10 months before transplantation. Only 17/178 (9.5%) studies were abnormal. The mean follow-up was 38 months (SD: 10). Of the patients with normal MPS, only 2 (1.2%) presented cardiovascular events, both with studies performed more than 2years before the procedure. There were no deaths of cardiovascular origin. Conclusions MPS is a safe and reliable technique for cardiovascular assessment of patients who are candidates for liver transplantation, given the low rate of false negatives during follow-up (AU)

Rendimiento diagnóstico de un nuevo software de aprendizaje profundo para corrección de atenuación en la imagen de perfusión miocárdica utilizando una cámara CZT cardiodedicada. Experiencia en la práctica clínica / Diagnostic performance of a novel deep learning attenuation correction software for MPI using a cardio dedicated CZT camera: Experience in the clinical practice

Objetivo Evaluar el rendimiento diagnóstico de un nuevo software de aprendizaje profundo para corrección de atenuación (SAPCA) en imágenes de perfusión miocárdica (IPM) utilizando una cámara cardiodedicada de cadmio-cinc-telurio (CZT) con correlación con angiografía coronaria (AC) para el diagnóstico de enfermedad arterial coronaria (EAC) en una población de alto riesgo. Métodos Estudio retrospectivo de 300 pacientes (196 varones [65%], edad media de 68 años) desde septiembre de 2014 hasta octubre de 2019. Posteriormente realizaron una IPM, seguida de AC dentro de los 6 meses posteriores a la IPM. La probabilidad media pretest para EAC según los criterios de la Sociedad Europea de Cardiología fue del 37%. La IPM se realizó en una cámara CZT cardio dedicada (D-SPECT® Spectrum Dynamics) usando un protocolo de 2 días, de acuerdo con las guías de la Sociedad Europea de Medicina Nuclear (EANM). La IPM fue evaluada con y sin el SAPCA. Resultados La precisión diagnóstica global de la IPM sin el SAPCA para identificar pacientes con cualquier EAC obstructiva en la AC fue del 87%, sensibilidad del 94%, especificidad del 57%, valor predictivo positivo del 91% y valor predictivo negativo del 64%. Utilizando el SAPCA, la precisión diagnóstica global fue del 90%, la sensibilidad del 91%, la especificidad del 86%, el valor predictivo positivo del 97% y el valor predictivo negativo del 66%. Conclusión El uso del novel SAPCA mejora el rendimiento diagnóstico de la IPM usando la cámara CZT D-SPECT®, especialmente reduciendo el número de resultados falsos positivos al reducir los artefactos (AU)

urpose To evaluate the diagnostic performance of a novel deep learning attenuation correction software (SAPCA) for myocardial perfusion imaging (MPI) using a cadmium-zinc-telluride (CZT) cardio dedicated camera with invasive coronary angiography (ICA) correlation for the diagnosis of coronary artery disease (CAD) in a high-risk population. Methods Retrospective study of 300 patients (196 males [65%], mean age 68 years) from September 2014 to October 2019 undergoing MPI, followed by ICA and evaluated by means of quantitative angiography software, within six months after the MPI. The mean pre-test probability score for coronary disease according to the European Society of Cardiology criteria was 37% for the whole cohort. The MPI was performed in a dedicated CZT cardio camera (D-SPECT® Spectrum Dynamics) with a two-day protocol, according to the European Association of Nuclear Medicine guidelines. MPI was retrospectively evaluated with and without the SAPCA. Results The overall diagnostic accuracy of MPI without SAPCA to identify patients with any obstructive CAD at ICA was 87%, Sensitivity 94%, Specificity 57%, positive predictive value 91% and negative predictive value 64%. Using SAPCA the overall diagnostic accuracy was 90%, sensitivity 91%, specificity 86%, positive predictive value 97% and negative predictive value 66%. Conclusion Use of the novel SAPCA enhances performance of the MPI using the CZT D-SPECT® camera and achieves improved results, especially avoiding artefacts and reducing the number of false positive results (AU)

10-year experience of utilizing a stress-first SPECT myocardial perfusion imaging.

BACKGROUND: Despite its potential benefits, the utilization of stress-only protocol in clinical practice has been limited. We report utilizing stress-first single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). METHODS: We assessed 12,472 patients who were referred for SPECT-MPI between 2013 and 2020. The temporal changes in frequency of stress-only imaging were assessed according to risk factors, mode of stress, prior coronary artery disease (CAD) history, left ventricular function, and symptom status. The clinical endpoint was all-cause mortality. RESULTS: In our lab, stress/rest SPECT-MPI in place of rest/stress SPECT-MPI was first introduced in November 2011 and was performed more commonly than rest/stress imaging after 2013. Stress-only SPECT-MPI scanning has been performed in 30-34% of our SPECT-MPI studies since 2013 (i.e.. 31.7% in 2013 and 33.6% in 2020). During the study period, we routinely used two-position imaging (additional prone or upright imaging) to reduce attenuation and motion artifact and introduced SPECT/CT scanner in 2018. The rate of stress-only study remained consistent before and after implementing the SPECT/CT scanner. The frequency of stress-only imaging was 43% among patients without a history of prior CAD and 19% among those with a prior CAD history. Among patients undergoing treadmill exercise, the frequency of stress-only imaging was 48%, while 32% among patients undergoing pharmacologic stress test. In multivariate Cox analysis, there was no significant difference in mortality risk between stress-only and stress/rest protocols in patients with normal SPECT-MPI results (p = 0.271). CONCLUSION: Implementation of a stress-first imaging protocol has consistently resulted in safe cancellation of 30% of rest SPECT-MPI studies.

Predicting long-term time to cardiovascular incidents using myocardial perfusion imaging and deep convolutional neural networks.

Myocardial perfusion imaging (MPI) is a clinical tool which can assess the heart's perfusion status, thereby revealing impairments in patients' cardiac function. Within the MPI modality, the acquired three-dimensional signals are typically represented as a sequence of two-dimensional grayscale tomographic images. Here, we proposed an end-to-end survival training approach for processing gray-scale MPI tomograms to generate a risk score which reflects subsequent time to cardiovascular incidents, including cardiovascular death, non-fatal myocardial infarction, and non-fatal ischemic stroke (collectively known as Major Adverse Cardiovascular Events; MACE) as well as Congestive Heart Failure (CHF). We recruited a total of 1928 patients who had undergone MPI followed by coronary interventions. Among them, 80% (n = 1540) were randomly reserved for the training and 5- fold cross-validation stage, while 20% (n = 388) were set aside for the testing stage. The end-to-end survival training can converge well in generating effective AI models via the fivefold cross-validation approach with 1540 patients. When a candidate model is evaluated using independent images, the model can stratify patients into below-median-risk (n = 194) and above-median-risk (n = 194) groups, the corresponding survival curves of the two groups have significant difference (P < 0.0001). We further stratify the above-median-risk group to the quartile 3 and 4 group (n = 97 each), and the three patient strata, referred to as the high, intermediate and low risk groups respectively, manifest statistically significant difference. Notably, the 5-year cardiovascular incident rate is less than 5% in the low-risk group (accounting for 50% of all patients), while the rate is nearly 40% in the high-risk group (accounting for 25% of all patients). Evaluation of patient subgroups revealed stronger effect size in patients with three blocked arteries (Hazard ratio [HR]: 18.377, 95% CI 3.719-90.801, p < 0.001), followed by those with two blocked vessels at HR 7.484 (95% CI 1.858-30.150; p = 0.005). Regarding stent placement, patients with a single stent displayed a HR of 4.410 (95% CI 1.399-13.904; p = 0.011). Patients with two stents show a HR of 10.699 (95% CI 2.262-50.601; p = 0.003), escalating notably to a HR of 57.446 (95% CI 1.922-1717.207; p = 0.019) for patients with three or more stents, indicating a substantial relationship between the disease severity and the predictive capability of the AI for subsequent cardiovascular inciidents. The success of the MPI AI model in stratifying patients into subgroups with distinct time-to-cardiovascular incidents demonstrated the feasibility of proposed end-to-end survival training approach.

Quantitating myocardial fibrosis using extracellular extravascular volume determined from computed tomography myocardial perfusion imaging.

PURPOSE: Both of extracellular extravascular volume (EEV) and extracellular volume fraction (ECV) were proposed to quantify enlargement of myocardial interstitial space due to myocardium loss or fibrosis. The study aimed to investigate the feasibility of using EEV derived from myocardial computed tomography (CT) perfusion imaging (VPCT) and extracellular volume quantification with single-energy subtraction CT (ECV- SECT) for quantifying myocardial fibrosis. METHODS: In this study, 17 patients with suspected and known coronary artery disease underwent examination using a dual-source CT scanner. The EEV- VPCT was derived from dynamic whole-heart myocardial perfusion imaging, and the ECV_SECT was calculated from late-enhanced images 5 min after bolus contrast injection by subtracting the noncontrast baseline. The late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging was used as a reference. RESULTS: In total, 11 patients and 73 segments exhibited positivity for LGE on CMR imaging. These were classified into three groups according to the segments: fibrotic segments (group I, n = 73), nonfibrotic segments in LGE-positive patients (group II, n = 103), and segments in LGE-negative patients (group III, n = 80). ECV- SECT, EEV- VPCT, myocardial blood flow (MBF), and myocardial blood volume (MBV) significantly differed among these groups (all P < 0.05). ECV- SECT was significantly higher and EEV- VPCT, MBF, and MBV were significantly lower in fibrotic myocardial segments than in nonfibrotic ones (all P < 0.01). ECV- SECT and EEV- VPCT independently affected myocardial fibrosis. There was no significant correlation between ECV- SECT and EEV- VPCT. The capability of EEV- VPCT to diagnose myocardial fibrosis was equivalent to that of ECV- SECT (area under the curve: 0.798 vs. 0.806, P = 0.844). ECV- SECT of > 41.2% and EEV- VPCT of < 10.3% indicated myocardial fibrosis. CONCLUSIONS: EEV- VPCT is actually first-pass distribution volume that can feasibly be used to quantify myocardial fibrosis. Furthermore, the diagnostic efficacy of EEV- VPCT is comparable to that of ECV- SECT.

Role of the clinical radiopharmacist in patient safety during myocardial perfusion imaging with vasodilator stress agents.

AIM: To assess the radiopharmacist's role in a multidisciplinary team focused on the contraindications of regadenoson in order to ensure the safe use of pharmacologic vasodilator stress agents in patients undergoing SPECT-MPI. METHODS: We ambispectively studied its safe use in 1905 patients (54.1% female, mean age: 66.6±11.7 years, range: 20-95 years). Sex, age, medical history, medications, drug allergies, and contraindications for stress testing were registered together with recommendations for the nuclear physician in charge. RESULTS: Detected contraindications and corresponding recommendations were as follows: risk factors for QTc interval prolongation 7.5% - measurement of QTc interval previously to test and monitor ECG; prior stroke or TIA 4.2% - consider carotid stenosis assessment; salicylates/sulfonamides allergy 3.1% - use 99mTc-sestamibi; epilepsy or risk factors for seizures 2.4% - use of adenosine or reconsider test indication; systemic corticosteroid therapy for severe COPD 1.3% - reassessment of patient's condition; acute exacerbation of COPD 0.8% - defer test until acute episode is over; severe asthma 0.4% - do not perform test; methylxanthine ingestion 0.3% - avoid consumption previously; other 6.1% - evaluation of other contraindications. No contraindications were detected in 73.6% of patients. The test was canceled due to absolute contraindications in 2.9% of the requests. CONCLUSIONS: Working in a systematic way, the radiopharmacist was able to detect a high number of issues related to regadenoson, with one out of four patients presenting some clinical contraindication. The recommendations given by the radiopharmacist were well accepted by the nuclear physicians who changed their approach contributing to increase the safety of patients referred for MPI.

Left ventricular mechanical dyssynchrony after chemotherapy in breast cancer patients with normal rest gated SPECT-MPI.

OBJECTIVES: Early diagnosis of chemotherapy-induced cardiotoxicity plays an important role in preventing heart failure. The main aim of our study was to assess left ventricular (LV) dyssynchrony measured by phase analysis of gated single-photon emission computed tomography (SPECT) as an early sign of cardiotoxicity after breast cancer chemotherapy. METHODS: This cross-sectional study was conducted on patients with stage ≤ 3 breast cancer and no history of cardiovascular disease or diabetes. After mastectomy, the patients underwent rest gated SPECT myocardial perfusion imaging (MPI). Sixty patients with normal gated SPECT-MPI were selected and the imaging was performed after chemotherapy with doxorubicin, cyclophosphamide and paclitaxel. LV function and contractility parameters were extracted by QGS software and the results were compared with the t test method. The abnormality of at least one of the three phase analysis indices was considered as left ventricular dyssynchrony (LVD). RESULTS: The average LV end-systolic volume and ejection fraction (LVEF) before and after chemotherapy were (16.2 ± 8.0 ml and 21.6 ± 11.6 ml) and (73.4 ± 7.9% and 67.5 ± 9.2%) respectively, which showed a significant decrease (P < 0.05). In 2 patients (3.3%), the LVEF decreased to less than 50% after chemotherapy. The average parameters of left ventricular contractility before and after chemotherapy were, respectively, as follows: PHB (24.1 ± 7.5 and 33.8 ± 16.4), PSD (9.4 ± 6.1 and 5.7 ± 1.9) and entropy (28.9 ± 7.1 and 35.6 ± 9.7), which showed a significant increase (P < 0.05). LVD was observed in 14 patients (23.4%) after chemotherapy and prevalence of LVD was significantly higher in patients who had received a cumulative dose of doxorubicin of more than 400 mg/m2 (P = 0.005). There was no relationship between age and body mass index with the incidence of LVD after chemotherapy (P > 0.05). CONCLUSION: Using phase analysis of gated SPECT-MPI, chemotherapy-induced LVD was seen in a significant number of patients with breast cancer, especially with a high cumulative dose of doxorubicin. LVD might indicate chemotherapy-induced cardiotoxicity before LVEF becomes abnormal.

Impact of Absolute Myocardial Blood Flow Quantification on the Diagnostic Performance of PET-Based Perfusion Scans Using 82Rubidium.

BACKGROUND: Guidelines propose the inclusion of quantitative measurements from 82Rubidium positron emission tomography (RbPET) to discriminate obstructive coronary artery disease (CAD). However, the effect on diagnostic accuracy is unknown. The aim was to investigate the optimal RbPET reading algorithm for improved identification of obstructive CAD. METHODS: Prospectively enrolled patients (N=400) underwent RbPET and invasive coronary angiography with fractional flow reserve and quantitative coronary angiography. Quantitative measurements (myocardial blood flow (MBF), MBF reserve, transient ischemic dilatation) by RbPET were step-wisely added to a qualitative assessment by the summed stress score based on their diagnostic accuracy of obstructive CAD by invasive coronary angiography-fractional flow reserve. Prespecified cutoffs were summed stress score ≥4, hyperemic MBF 2.00 mL/g per min, and MBF reserve 1.80, respectively. Hemodynamically obstructive CAD was defined as >90% diameter stenosis or invasive coronary angiography-fractional flow reserve ≤0.80, and sensitivity analyses included a clinically relevant reference of anatomically severe CAD (>70% diameter stenosis by invasive coronary angiography-quantitative coronary angiography). RESULTS: Hemodynamically obstructive CAD was present in 170/400 (42.5%) patients. Stand-alone summed stress score showed a sensitivity and specificity of 57% and 93%, respectively, while hyperemic MBF showed similar sensitivity (61%, P=0.57) but lower specificity (85%, P=0.008). With increased discrimination by receiver-operating characteristic curves (0.78 versus 0.85; P<0.001), combining summed stress score, MBF and MBF reserve showed the highest sensitivity of 77% but lower specificity of 74% (P<0.001 for both comparisons). Against anatomically severe CAD, all measures independently yielded high discrimination ≥0.90 with increased sensitivity and lower specificity by additional quantification. CONCLUSIONS: The inclusion of quantitative measurements to a RbPET read increases in the identification of obstructive CAD. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03481712.

Comparative Effectiveness of PET and SPECT MPI for Predicting Cardiovascular Events After Kidney Transplant.

BACKGROUND: Advanced chronic kidney disease is associated with high cardiovascular risk, even after kidney transplant. Pretransplant cardiac testing may identify patients who require additional assessment before transplant or would benefit from risk optimization. The objective of the current study was to determine the relative prognostic utility of pretransplant positron emission tomography (PET) and single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) for posttransplant major adverse cardiovascular events (MACEs). METHODS: We retrospectively followed patients who underwent MPI before kidney transplant for the occurrence of MACE after transplant including myocardial infarction, stroke, heart failure, and cardiac death. An abnormal MPI result was defined as a total perfusion deficit >5% of the myocardium. To determine associations of MPI results with MACE, we utilized Cox hazard regression with propensity weighting for PET versus SPECT with model factors, including demographics and cardiovascular risk factors. RESULTS: A total of 393 patients underwent MPI (208 PET and 185 SPECT) and were followed for a median of 5.9 years post-transplant. Most were male (58%), median age was 58 years, and there was a high burden of hypertension (88%) and diabetes (33%). A minority had abnormal MPI (n=58, 15%). In propensity-weighted hazard regression, abnormal PET result was associated with posttransplant MACE (hazard ratio, 3.02 [95% CI, 1.78-5.11]; P<0.001), while there was insufficient evidence of an association of abnormal SPECT result with MACE (1.39 [95% CI, 0.72-2.66]; P=0.33). The explained relative risk of the PET result was higher than the SPECT result (R2 0.086 versus 0.007). Normal PET was associated with the lowest risk of MACE (2.2%/year versus 3.6%/year for normal SPECT; P<0.001). CONCLUSIONS: Kidney transplant recipients are at high cardiovascular risk, despite a minority having obstructive coronary artery disease on MPI. PET MPI findings predict posttransplant MACE. Normal PET may better discriminate lower risk patients compared with normal SPECT, which should be confirmed in a larger prospective study.

Machine learning models for positron emission tomography myocardial perfusion imaging.

Machine learning has the potential to improve patient care by automating the assessment of medical imaging. Machine learning models have been developed to identify ischaemia and scar on rest and stress myocardial perfusion imaging from positron emission tomography (PET). Application of these tools could aid reporting of PET by highlighting patients and vessels likely to have abnormalities. How this information should be integrated into clinical practice and the impact on patient management or outcomes is not currently known.

Rationale and design of the RAPID-WATER-FLOW trial: Radiolabeled perfusion to identify coronary artery disease using water to evaluate responses of myocardial FLOW.

OBJECTIVES: The objective of this study was to determine the diagnostic performance of 15O-water positron emission tomography (PET) myocardial perfusion imaging to detect coronary artery disease (CAD) using the truth-standard of invasive coronary angiography (ICA) with fractional flow reserve (FFR) or instantaneous wave-Free Ratio (iFR) or coronary computed tomography angiogram (CCTA). BACKGROUND: 15O-water has a very high first-pass extraction that allows accurate quantification of myocardial blood flow and detection of flow-limiting CAD. However, the need for an on-site cyclotron and lack of automated production at the point of care and relatively complex image analysis protocol has limited its clinical use to date. METHODS: The RAPID WATER FLOW study is an open-label, multicenter, prospective investigation of the accuracy of 15O-water PET to detect obstructive angiographic and physiologically significant stenosis in patients with suspected CAD. The study will include the use of an automated system for producing, dosing, and injecting 15O-water and enrolling approximately 215 individuals with suspected CAD at approximately 10 study sites in North America and Europe. The primary endpoint of the study is the diagnostic sensitivity and specificity of the 15O-water PET study using the truth-standard of ICA with FFR or iFR to determine flow-limiting stenosis, or CCTA to rule out CAD and incorporating a quantitative analytic platform developed for the 15O-water PET acquisitions. Sensitivity and specificity are to be considered positive if the lower bound of the 95% confidence interval is superior to the threshold of 60% for both, consistent with prior registration studies. Subgroup analyses include assessments of diagnostic sensitivity, specificity, and accuracy in female, obese, and diabetic individuals, as well as in those with multivessel disease. All enrolled individuals will be followed for adverse and serious adverse events for up to 32 hours after the index PET scan. The study will have >90% power (one-sided test, α = 0.025) to test the hypothesis that sensitivity and specificity of 15O-water PET are both >60%. CONCLUSIONS: The RAPID WATER FLOW study is a prospective, multicenter study to determine the diagnostic sensitivity and specificity of 15O-water PET as compared to ICA with FFR/iFR or CCTA. This study will introduce several novel aspects to imaging registration studies, including a more relevant truth standard incorporating invasive physiologic indexes, coronary CTA to qualify normal individuals for eligibility, and a more quantitative approach to image analysis than has been done in prior pivotal studies. CLINICAL TRIAL REGISTRATION INFORMATION: Clinical-Trials.gov (#NCT05134012).