Clinical Impact of Assessment of Myocardial Flow Reserve in Identifying the Cause of Chest Discomfort. / Impacto Clínico da Avaliação da Reserva de Fluxo Miocárdico na Identificação da Causa do Desconforto Torácico.

BACKGROUND: Gamma cameras with cadmium-zinc telluride (CZT) detectors allowed the quantification of myocardial flow reserve (MBF), which can increase the accuracy of myocardial perfusion scintigraphy (MPS) to detect the cause of chest discomfort. OBJECTIVE: To assess the clinical impact of MBF to detect the cause of chest discomfort. METHODS: 171 patients with chest discomfort who underwent coronary angiography or coronary CT angiography also underwent MPS and MBF in a time interval of <30 days. The acquisitions of dynamic imaging of rest and stress were initiated simultaneously with the 99mTc injection sestamibi (10 and 30mCi, respectively), both lasting eleven minutes, followed by immediately acquiring perfusion images for 5 minutes. The stress was performed with dipyridamole. A global or per coronary territory MBF <2.0 was classified as abnormal. RESULTS: The average age was 65.9±10 years (60% female). The anatomical evaluation showed that 115 (67.3%) patients had coronary obstruction significant, with 69 having abnormal MPs and 91 having abnormal MBF (60.0% vs 79.1%, p<0.01). Among patients without obstruction (56 - 32.7%), 7 had abnormal MPS, and 23 had reduced global MBF. Performing MBF identified the etiology of the chest discomfort in 114 patients while MPS identified it in 76 (66.7% vs 44.4%, p<0.001). CONCLUSION: MBF is a quantifiable physiological measure that increases the clinical impact of MPS in detecting the cause of chest discomfort through greater accuracy for detecting obstructive CAD, and it also makes it possible to identify the presence of the microvascular disease.

FUNDAMENTO: Gama-câmaras com detectores de telureto-cádmio-zinco (CZT) permitiram a quantificação da reserva de fluxo miocárdico (RFM), podendo aumentar a acurácia da cintilografia miocárdica de perfusão (CMP) para detectar a causa do desconforto torácico. OBJETIVO: Avaliar o impacto clínico da RFM para detectar a causa do desconforto torácico. MÉTODOS: 171 pacientes com desconforto torácico que foram submetidos a coronariografia ou angiotomografia de coronárias também realizaram CMP e RFM num intervalo de tempo <30 dias. As aquisições das imagens dinâmicas de repouso e estresse foram iniciadas simultaneamente à injeção de 99mTc sestamibi (10 e 30mCi, respectivamente), ambas com duração de onze minutos, seguidas imediatamente pela aquisição das imagens de perfusão durante 5 minutos. O estresse foi realizado com dipiridamol. Uma RFM global ou por território coronariano <2,0 foi classificada como anormal. RESULTADOS: A idade média foi de 65,9±10 anos (60% do sexo feminino). A avaliação anatômica mostrou que 115 (67,3%) pacientes apresentavam obstrução coronariana significativa, sendo que, 69 apresentavam CMP anormal e 91 apresentavam RFM anormal (60,0% vs. 79,1%, p<0,01). Dentre os pacientes sem obstrução (56 ­ 32,7%), 7 tinham CMP anormais e 23 tinham RFM global reduzida. A realização da RFM identificou a etiologia do desconforto torácico em 114 pacientes enquanto a CMP identificou em 76 (66,7% vs. 44,4%, p<0,001). CONCLUSÃO: A RFM é uma medida fisiológica quantificável que aumenta o impacto clínico da CMP na detecção da causa do desconforto torácico através de uma maior acurácia para detecção de DAC obstrutiva e ainda possibilita identificar a presença de doença microvascular.

DNA damage and repair in patients undergoing myocardial perfusion single-photon emission computed tomography.

As patient exposure to ionizing radiation from medical imaging and its risks are continuing issues, this study aimed to evaluate DNA damage and repair markers after myocardial perfusion single-photon emission computed tomography (MPS). Thirty-two patients undergoing Tc-99m sestamibi MPS were studied. Peripheral blood was collected before radiotracer injection at rest and 60-90 min after injection. The comet assay (single-cell gel electrophoresis) was performed with peripheral blood cells to detect DNA strand breaks. Three descriptors were evaluated: the percentage of DNA in the comet tail, tail length, and tail moment (the product of DNA tail percentage and tail length). Quantitative PCR (qPCR) was performed to evaluate the expression of five genes related to signaling pathways in response to DNA damage and repair (ATM, ATR, BRCA1, CDKN1A, and XPC). Mann-Whitney's test was employed for statistical analysis; p < 0.05 was considered significant. Mean Tc-99m sestamibi dose was 15.1 mCi. After radiotracer injection, comparing post-exposure to pre-exposure samples of each of the 32 patients, no statistically significant differences of the DNA percentage in the tail, tail length or tail moment were found. qPCR revealed increased expression of BRCA1 and XPC, without any significant difference regarding the other genes. No significant increase in DNA strand breaks was detected after a single radiotracer injection for MPS. There was activation of only two repair genes, which may indicate that, in the current patient sample, the effects of ionizing radiation on the DNA were not large enough to trigger intense repair responses, suggesting the absence of significant DNA damage.

Correlates of markers of dyssynchrony in patients with STEMI and multivessel disease: an analysis from the IAEA SPECT STEMI trial.

BACKGROUND: In this substudy of the Value of Gated-SPECT MPI for Ischemia- Guided PCI of non-culprit vessels in STEMI Patients with Multi vessel Disease after primary PCI trial after primary PCI we aim to assess if infarct size affects conventional measures of dyssynchrony at rest. Additionally, we explore if there is an independent correlation of stress-inducible ischemia with dyssynchrony at rest. METHODS: The 48 patients with imaging at randomization were analyzed. Gated-single-photon emission computed tomography (SPECT) MPI with vasodilator stress and technetium-99m-labeled tracers was performed. The phase histogram bandwidth (HBW), phase SD, and entropy were obtained with the QGS software. Correlation between dyssynchrony at rest and infarct size and inducible ischemia was performed using the Spearman test. RESULTS: According to normal database limits dyssynchrony parameters at rest were abnormal for men. In women only HBW was abnormal. Correlation between the summed rest score with dyssynchrony was significant only for entropy ( P  = 0.035). No correlation was observed for dyssynchrony and stress-induced ischemia. CONCLUSION: Entropy, as a measure of dyssynchrony, has potential in the assessment of patients with STEMI and multivessel disease after primary PCI. Smaller residual myocardial scars in PCI-reperfused patients with STEMI may contribute to the lack of correlation between dyssynchrony at rest and infarct size and stress-induced ischemia, respectively.

Temporal trends in the contribution of modifiable cardiovascular risk factors to cardiovascular and all-cause mortality in patients undergoing myocardial perfusion imaging in a large city in Brazil.

BACKGROUND: Most cardiovascular (CV) events stem from modifiable risk factors, but it remains uncertain whether their impact on mortality has decreased in recent years as a result of treatment, particularly in low- and middle-income countries. We evaluated the temporal trends in the population attributable fraction (PAF) of modifiable risk factors to CV mortality in patients undergoing myocardial perfusion imaging (MPI) for suspected coronary artery disease in a large city in Brazil. METHODS: The cohort comprised 25,127 patients without established CV disease undergoing MPI in a referral center in Curitiba, Brazil, from 2010 to 2018. Baseline demographic, clinical and risk factors were prospectively collected. Modifiable risk factors encompassed hypertension, dyslipidemia, diabetes mellitus, sedentary lifestyle, obesity, and smoking. The primary outcome was CV death occurring up to 4 years of follow-up. The PAF of each risk factor was calculated for each triennium using multivariable Cox proportional regression models, adjusting for age, sex and family history of premature coronary disease. RESULTS: Over 9 years, there were 1438 deaths, 444 due to CV causes. In the first triennium, sedentary lifestyle exhibited the highest PAF (49%) for CV death, followed by hypertension (17%), diabetes mellitus (8%) and smoking habit (6%). The PAF for all risk factors combined remained relatively stable thorough the triennia (2010-2012: 57% vs 2013-2015: 64% vs 2016-2018: 47%, p = NS). CONCLUSION: In this large cohort of patients referred to MPI, the PAF of modifiable CV risk factors did not diminish in the last decade, with sedentary lifestyle having the largest contribution for CV mortality. CONDENSED ABSTRACT: This study examinated temporal trends in the impact of modifiable cardiovascular (CV) risk factors on CV and overall mortality in a cohort of 25,127 patients undergoing myocardial perfusion imaging from 2010 to 2018. Sedentary behavior consistently had the greatest impact on both CV and overall mortality, followed by hypertension and diabetes. Smoking had a lesser effect, while obesity showed no independent association with the outcomes. The contributions of these modifiable CV risk factors remained stable over the study period, suggesting that interventions promoting physical activity may be essential in mitigating the burden of CV disease.

Relationship between transient ischemic dilatation and changes in heart rate during gated SPECT acquisition in a low-risk population without perfusion defects.

OBJECTIVES: Transient ischemic dilatation (TID) in myocardial perfusion single photon emission computed tomography (SPECT) is considered a marker of poor prognosis. However, it has been suggested that some cases are due to apparent volumetric changes secondary to differences in heart rate (HR) at the time of acquisition. We assessed the correlation between transient dilatation and HR in low risk patients with no perfusion defects. METHODS: We retrospectively analyzed patients sent for 99mTc-MIBI SPECT using a 2-day protocol. We recorded the median HR during acquisition and the HR difference (HRD) between the rest and post-stress. We obtained the medium ventricular volume, end-diastolic volume (EDV), and end-systolic volume (ESV). We included patients in which TID using medium ventricular volume (TIDMV) was ≥1.2. TID was also calculated for the EDV and ESV (TIDEDV, TIDESV). We excluded patients with known coronary artery disease, perfusion defects, various ECG disorders, positive stress test, or ESV < 10 ml. RESULTS: From a total of 2006 patients, 63 (50 exercise, 13 dipyridamole) met the criteria for analysis (age 63.8 ±â€…9.7, 44 men). TIDMV was 1.29 ±â€…0.09 and HRD 9.8 beats per minute (BPM) (range -10 to 41). There was positive correlation between HRD and TIDMV ( r  = 0.51, P  < 0.001) and TIDEDV ( r  = 0.5, P  < 0.001), but not TIDESV ( r  = 0.23, P  = 0.07). Correlation was stronger when HRD was ≥10 BPM ( r  = 0.67, P  < 0.001). CONCLUSION: TID without perfusion defects should be interpreted with caution in the presence of HRD ≥ 10 BPM during post-stress acquisition.

Concordance between vessel-specific and vascular territory coronary functional assessment: A comparison of quantitative flow ratio and myocardial perfusion scintigraphy.

BACKGROUND: Quantitative flow ratio (QFR) and myocardial perfusion scintigraphy (MPS) are utilized for assessing coronary artery disease (CAD) significance. We aimed to analyze their concordance and prognostic impact. AIMS: We aimed to analyze the concordance between QFR and MPS and their risk stratification. METHODS: Patients with invasive coronary angiography and MPS were categorized as concordant if QFR ≤ 0.80 and summed difference score (SDS) ≥ 4 or if QFR > 0.80 and SDS < 4; otherwise, they were discordant. Concordance was classified by coronary territory involvement: total (three territories), partial (two territories), poor (one territory), and total discordance (zero territories). Leaman score assessed coronary atherosclerotic burden. RESULTS: 2010 coronary territories (670 patients) underwent joint QFR and MPS analysis. MPS area under the curve for QFR ≤ 0.80 was 0.637. Concordance rates were total (52.5%), partial (29.1%), poor (15.8%), and total discordance (2.6%). Most concordance occurred in patients without significant CAD or with single-vessel disease (89.5%), particularly without MPS perfusion defects (91.5%). Leaman score (odds ratio [OR]: 0.839, 95% confidence interval [CI]: 0.805-0.875, p < 0.001) and MPS perfusion defect (summed stress score [SSS] ≥ 4) (OR: 0.355, 95% CI: 0.211-0.596, p < 0.001) were independent predictors for discordance. After 1400 days, no significant difference in death/myocardial infarction was observed based on MPS assessment, but Leaman score, functional Leaman score, and average QFR identified higher risk patients. CONCLUSIONS: MPS showed good overall accuracy in assessing QFR significance but substantial discordance existed. Predictors for discordance included higher atherosclerotic burden and MPS perfusion defects (SSS ≥ 4). Leaman score, QFR-based functional Leaman score, and average QFR provided better risk stratification for all-cause death and myocardial infarction than MPS.

Myocardial perfusion scintigraphy in the assessment of cardiovascular risk in adult liver transplantation.

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 2 years 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.

El puntaje de Framingham ayudaría en la estratificación del riesgo de pacientes con ergometría positiva y SPECT normal / The Framingham score could help in risk stratification of patients with positive ergometry and normal SPECT

Antecedentes. El valor pronóstico de una ergometría positiva en el contexto de imágenes tomográficas de perfusión miocárdica de estrés y reposo (SPECT) normales no está bien establecido. Objetivos. Documentar la incidencia de infarto, muerte y revascularización coronaria en pacientes con una ergometría positiva de riesgo intermedio e imágenes de perfusión SPECT normales, y explorar el potencial valor del puntaje de riesgo de Framingham en la estratificación pronóstica de estos pacientes. Métodos. Cohorte retrospectiva integrada por pacientes que habían presentado síntomas o hallazgos electrocardiográficos compatibles con enfermedad arterial coronaria durante la prueba de esfuerzo, con criterios de riesgo intermedio en la puntuación de Duke y perfusión miocárdica SPECT normal. Fueron identificados a partir de la base de datos del laboratorio de cardiología nuclear del Instituto de Cardiología y Cirugía Cardiovascular de la ciudad de Posadas, Argentina. Resultados. Fueron elegibles 217 pacientes. El seguimiento fue de 3 1,5 años. La sobrevida libre de eventos (muerte,infarto de miocardio no fatal, angioplastia coronaria o cirugía de bypass de arteria coronaria) a uno, tres y cinco años fue significativamente menor (Log-rank test, p= 0,001) en el grupo con puntaje de Framingham alto o muy alto (77, 71y 59 %, respectivamente) que en el grupo de puntaje bajo o intermedio (89, 87 y 83 %). Tomando como referencia a los pacientes con riesgo bajo en el puntaje de Framingham, luego de ajustar por edad, sexo y puntaje de Duke, los pacientes categorizados en los estratos alto y muy alto riesgo del puntaje de Framingham presentaron una incidencia del evento combinado cercana al triple (hazard ratio [HR] 2,81; intervalo de confianza [IC] del 95 % 0,91 a 8,72; p= 0,07 y HR 3,61;IC 95 % 1,23 a 10,56; p= 0,019 respectivamente). Conclusiones. La estimación de riesgo con el puntaje de Framingham sería de ayuda en la estratificación pronóstica de los pacientes con ergometría positiva y SPECT normal. (AU)

Background. The prognostic value of positive exercise testing with normal SPECT myocardial perfusion imaging is not well established. Objectives. To document the incidence of infarction, death, and coronary revascularization in patients with a positive intermediate-risk exercise test and normal SPECT perfusion images and to explore the potential value of the Framingham Risk Score in the prognostic stratification of these patients. Methods. A retrospective cohort comprised patients who presented symptoms or electrocardiographic findings compatible with coronary artery disease during the stress test, with intermediate risk criteria in the Duke score and normal SPECT myocardial perfusion. They were identified from the database of the nuclear cardiology laboratory of the Instituto de Cardiología y Cirugía Cardiovascular of Posadas, Argentina. Results. 217 patients were eligible. Follow-up was 3 1.5 years. Event-free survival (death, non-fatal myocardial infarction, coronary angioplasty, or coronary artery bypass surgery) at one, three, and five years was significantly lower (Log-ranktest, p: 0.001) in the group with a score of Framingham high or very high (77, 71 and 59 %, respectively) than in the lowor intermediate score group (89, 87 and 83 %). Taking as reference the low-risk patients in the Framingham score, after adjusting for age, sex, and Duke score, the patients categorized in the high-risk and very high-risk strata showed about three times higher incidence of the combined event (hazard ratio [HR] 2.81; 95 % confidence interval [CI] 0.91 to 8.72;p=0.07 and HR 3.61; 95 % CI 1.23 to 10.56; p=0.019 respectively). Conclusions. Risk estimation with the Framingham score would be helpful in the prognostic stratification of patients with positive exercise testing and normal SPECT. (AU)

El dilema clínico frente a los pacientes con ergometría positiva y prueba de perfusión miocárdica con SPECT normal / The clinical dilemma facing patients with positive stress test and normal SPECT myocardial perfusion imaging

La evaluación de la perfusión miocárdica con SPECT combina una prueba de esfuerzo (ergometría o estrés farmacológico) junto a imágenes de perfusión con radioisótopos. Este estudio es útil para establecer el diagnóstico de enfermedad arterial coronaria, estratificar el riesgo de infarto y tomar decisiones terapéuticas. Un resultado normal aporta un alto valor predictivo negativo, es decir, una muy baja probabilidad de que el paciente presente eventos cardiovasculares. El hallazgo de signos de isquemia en la ergometría podría poner en jaque el valor predictivo negativo de una perfusión normal. En presencia de este resultado, el paso siguiente es evaluar los predictores de riesgo en la ergometría, el riesgo propio del paciente en función de los antecedentes clínicos y el puntaje cálcico coronario, cuando este se encuentra disponible. Ante la presencia concomitante de otros marcadores de riesgo se sugiere completar la evaluación con un estudio anatómico.El uso de nuevas tecnologías podría mejorar la precisión en la predicción de eventos. (AU)

Assessment of myocardial perfusion with SPECT combines a stress test (ergometry or pharmacological stress) with radioisotope perfusion imaging. This test is helpful to diagnose coronary artery disease, stratify the risk of heart attack, and make therapeutic decisions. A normal result provides a high negative predictive value; therefore, the probability of cardiovascular events is very low. Signs of ischemia on an ergometry could jeopardize the negative predictive value of normal perfusion. In this clinical setting, the next step is to evaluate the risk predictors in the stress test, the individual risk based on the clinical history, and the coronary calcium score when available. Given the simultaneous presence of other risk markers,completing the evaluation with an anatomical study is suggested. The use of new technologies could improve the accuracy of event prediction. (AU)

The Role and Advantages of Cardiac Magnetic Resonance in the Diagnosis of Myocardial Ischemia.

Ischemic heart disease continues to be the leading cause of death and disability worldwide. For the diagnosis of ischemic heart disease, some form of cardiac stress test involving exercise or pharmacological stimulation continues to play an important role, despite advances within modalities like computer tomography for the noninvasive detection and characterization of epicardial coronary lesions. Among noninvasive stress imaging tests, cardiac magnetic resonance (CMR) combines several capabilities that are highly relevant for the diagnosis of ischemic heart disease: assessment of wall motion abnormalities, myocardial perfusion imaging, and depiction of replacement and interstitial fibrosis markers by late gadolinium enhancement techniques and T1 mapping. On top of these qualities, CMR is also well tolerated and safe in most clinical scenarios, including in the presence of cardiovascular implantable devices, while in the presence of renal disease, gadolinium-based contrast should only be used according to guidelines. CMR also offers outstanding viability assessment and prognostication of cardiovascular events. The last 2019 European Society of Cardiology guidelines for chronic coronary syndromes has positioned stress CMR as a class I noninvasive imaging technique for the diagnosis of coronary artery disease in symptomatic patients. In the present review, we present the current state-of-the-art assessment of myocardial ischemia by stress perfusion CMR, highlighting its advantages and current shortcomings. We discuss the safety, clinical, and cost-effectiveness aspects of gadolinium-based CMR-perfusion imaging for ischemic heart disease assessment.

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.

BACKGROUND: Three-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. AIMS: To 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. METHODS: We 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. RESULTS: 474 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. CONCLUSION: Perfusion and dyssynchrony were the parameters which were most able to discriminate patients with 3VD from those who did not have CAD.

Eficacia y seguridad de SPECT/TC digital, con detectores digitales de conversión directa con tecnología CZT (cadmio, zinc, teluro) / Efficacy and safety of digital SPECT/CT, with direct conversion digital detectors with CZT technology (cadmium, zinc, tellurium)

INTRODUCCIÓN En los últimos años, se ha desarrollado la aplicación de una nueva tecnología: SPECT/TC digital, con detectores digitales de conversión directa con tecnología CZT (cadmio zinc teluro) que provee a los equipos, de alta resolución y contraste, con tiempos de estudio significativamente más cortos, ampliando de esta forma el campo de aplicación e incrementando el rendimiento de los equipos. En las "cámaras CZT", el cristal convencional de sodio/yodo (NaI) utilizado para la detección de rayos gamma ha sido reemplazado por un cristal de cadmio-zinc-teluro (CZT). Este cristal transforma directamente la señal inducida por los rayos gamma en impulsos eléctricos sin necesidad de fotodetectores. La interacción de un fotón gamma de 140 keV en los detectores CZT produce aproximadamente 30.000 electrones, 20 veces más que los producidos en un cristal de NaI convencional, mejorando la resolución energética por un factor de 2 en comparación con las cámaras Anger convencionales. La aportación más relevante de esta nueva tecnología respecto a la convencional sería la calidad de imagen, determinada por 3 factores: resolución energética, resolución espacial y sensibilidad. En el estudio de la perfusión coronaria, usando estas tecnologías, se ha desarrollado la imagen multimodal que surge de la necesidad de integrar la información anatómica (que define el árbol coronario morfológicamente) con la funcional (que refleja la afectación tisular de dicha enfermedad) con el fin de evaluar correctamente a los pacientes afectos de cardiopatía isquémica. Esta imagen multimodal se realiza de forma directa mediante equipos híbridos como el SPECT/TC que integran dos tecnologías en un mismo equipo permitiendo una mejor estratificación del riesgo del paciente. La fusión mediante el software de las imágenes de la perfusión tomadas con el SPECT con la anatómica de la TC ofrece información diagnóstica superior a la identificación aislada de la lesión y, además, esta información dual se puede obtener con procedimientos no invasivos y de forma ambulatoria. Recientemente la incorporación de receptores CZT en equipos no dedicados específicamente a la imagen cardiaca (equipos multipropósito o total body), han permitido la expansión del uso a la evaluación de otras zonas corporales donde los equipos tradicionales de SPECT-TC ya se estaban empleando. OBJETIVOS: El objetivo de este informe es describir la eficacia diagnóstica y la seguridad SPECT/TC con detectores digitales de conversión directa con tecnología CZT (cadmio, zinc, teluro) frente a equipos semejantes dotados de sensores convencionales, en la evaluación de la perfusión miocárdica en pacientes con cardiopatía isquémica. Como objetivo secundario se describirá la utilización de estos equipos en otras patologías y usos clínicos, en los que exista evidencia disponible. MÉTODOS: Tras la definición de las preguntas de investigación se definieron varias estrategias de búsqueda bibliográfica para diferentes bases de datos (MEDLINE, EMBASE, CENTRAL y Cochrane library). Las búsquedas se orientaron principalmente a conocer la efectividad y seguridad de acuerdo con las preguntas formuladas. Las búsquedas y la selección de la bibliografía se realizaron atendiendo a criterios diferenciados para los dos ámbitos de uso de la tecnología: la aplicación al estudio de la perfusión cardiaca y el uso en otras áreas. Para el primer caso se seleccionaron estudios que aportasen la mayor certeza en sus conclusiones, para la segunda parte se hizo una revisión panorámica con el objeto de identificar la mayor cantidad de ámbitos de utilización. La selección, depuración y síntesis de la información se realizó por duplicado y en caso de duda esta fue resulta por consenso. Para la evaluación de la calidad se utilizó la herramienta AMSTAR-2 para revisiones y seleccionada para estudios observacionales se empleó la herramienta Robins-I. La síntesis de la evidencia se realizó utilizando la metodología GRADE con la herramienta GRADE-Pro. Los resultados y las conclusiones fueron consensuados por el conjunto de los autores. RESULTADOS: Los resultados se estructuraron en dos partes: resultados de eficacia y seguridad de SPECT/TC CZT en la evaluación de la perfusión cardiaca y descripción de otras aplicaciones. EFICACIA Y SEGURIDAD DE SPECT/TC CZT PARA EL ANÁLISIS DE LA PERFUSIÓN CARDIACA. Pregunta 1: Efectividad en pacientes con sospecha de isquemia coronaria. Tras la búsqueda bibliográfica fue posible identificar una revisión sistemática cuyo objetivo era comparar el rendimiento diagnóstico entre SPECT-CZT y SPECT-convencional en pacientes con enfermedad coronaria confirmada mediante angiografía. Esta revisión fue calificada de baja calidad según criterios AMSTAR-II. La comparación de la eficacia diagnóstica entre ambas técnicas se realizó de forma indirecta pues los autores de la revisión no pudieron identificar trabajos que comparasen directamente ambas técnicas sobre una muestra de pacientes de una misma población. La revisión se centró en el análisis de la eficacia diagnóstica, medida en términos de sensibilidad y especificidad: Así, la sensibilidad estimada es de 85% [IC95% 79%-89%] para SPECT-Convencional frente a 89% [IC95% 86%-91%] para SPECT-CZT y la especificidad es 66% [IC95% 56%-74%] y 69% [IC95% 61%-75%]. El análisis de las curvas ROC muestra un área bajo la curva ligeramente mayor para SPECT-CZT área=0,89 [IC95% 0,86-0,92], con regiones de confianza y predicción bastante restringidas, en comparación con SPECT-C área=0,83 [IC95% 0,80-0,86]. (Test de hipótesis de la comparación p=0,03). Pregunta 2: Seguridad en pacientes con sospecha de isquemia coronaria. Como en otros estudios diagnósticos de imagen híbrida los principales riesgos están asociados con la potencial exposición a radiación. Se identificó un estudio observacional con grupo control apareado por edad, sexo e índice de masa corporal. En él se incluyeron pacientes remitidos a una sola institución para la evaluación de una posible enfermedad coronaria mediante SPECT, se cuantificó en cada uno de los pacientes la dosis total de radiación recibida en todo el proceso diagnóstico y de tratamiento hasta 90 días después de la indicación de la prueba, incluyendo la recibida en el SPECT, las angiografías, cateterismos y la intervención coronaria percutánea cuando esta fue realizada. Tanto el grupo intervención (SPECT-CZT) como los controles (SPECT-convencional) parecieron seguir la misma rutina diagnóstica y terapéutica según los hallazgos y necesidades indicadas por los profesionales responsables. Se evaluó el riesgo de sesgo de este trabajo mediante la herramienta Robins-I y fue calificado como de riesgo serio. Es preciso considerar, además, que esta evidencia es indirecta pues los pacientes no fueron evaluados con equipos híbridos, sino con equipos de SPECT no dotados de TC. El principal resultado mostrado es la diferencia de dosis recibida que entre los pacientes incluidos en el grupo expuesto a SPECT-CZT y los incluidos en el grupo de comparación fue estimada en -3,1 mSv [IC95% -4,32; -1,87]. OTRAS APLICACIONES La búsqueda permitió identificar inicialmente 35 referencias susceptibles de describir aplicaciones clínicas presentes o de pronta incorporación de la tecnología objeto del presente informe. Tras la selección y depuración de los trabajos identificados finalmente sólo 6 originales aportaron información útil. La aplicación no relacionada con la perfusión coronaria descrita con mayor frecuencia es el estudio de la perfusión vascular cerebral, posiblemente debido a la mejora de la resolución y la rapidez del análisis que han aportado los sensores de CZT. También se han descrito la utilidad para la detección y seguimiento de lesiones sólidas de origen tumoral o sospechosas de serlo, especialmente en lesiones de mama, sistema linfático y óseas. Finalmente, también se ha comunicado el empleo de los dispositivos objeto del informe en el análisis y cuantificación de la fracción de eyección del ventrículo izquierdo. CONCLUSIONES: Actualmente, el uso de CZT supone la actualización de una tecnología ya consolidada. La evidencia identificada para evaluar el beneficio del SPECT-TC CZT frente a SPECT-TC, aunque de mala calidad y siendo indirecta permite concluir que podría ser más eficaz en el estudio de la enfermedad isquémica coronaria. La dosis de radiación recibida en los pacientes que se les realiza SPECT/TC CZT parece ser menor respecto a los que se les realiza SPECT/ TC convencional, si bien, la calidad de la evidencia se ha considerado muy baja esencialmente, por el riesgo de sesgo y ser indirecta. La utilización de esta tecnología para otras indicaciones diferentes de la cardiaca está empezando a definirse, en el momento actual la descrita con mayor frecuencia podría ser el estudio de la perfusión vascular cerebral y el estudio de lesiones sólidas malignas o sospechosas de malignidad.

INTRODUCTION In recent years, the application of a new technology has been developed: digital SPECT/CT, with direct conversion digital detectors with CZT (cadmium zinc telluride) technology that provides equipment with high resolution and contrast with significantly shorter study times, expanding the field of application and increasing the performance of the equipment. In "CZT cameras", the conventional sodium/iodine (NaI) crystal used for gamma ray detection has been obtained by a cadmium-zinc-telluride (CZT) crystal. This crystal directly transforms the signal induced by gamma rays into electrical impulses without needing photodetectors. The interaction of a 140 keV gamma photon in CZT detectors produces approximately 30,000 electrons, 20 times more than those produced in a conventional NaI crystal, improving energy resolution by a factor of 2 compared to conventional Anger cameras. The most relevant contribution of this new technology compared to conventional technology would be image quality, determined by 3 factors: energy resolution, spatial resolution and sensitivity. In the study of coronary perfusion, using these technologies, multimodal imaging has been developed; it arises from the need to integrate anatomical information (which defines the coronary tree morphologically) with functional information (which reflects the tissue involvement of said disease), in order to correctly evaluate patients with ischemic heart disease. This multimodal image is performed directly using hybrid equipment such as SPECT/CT that integrates two technologies in the same equipment, achieving better patient risk stratification. The fusion, obtained by software, of the perfusion images taken with SPECT with the anatomical one of the CT offers diagnostic information superior to the isolated identification of the lesion and, furthermore, this dual information can be obtained with non-invasive procedures and on an outpatient basis. It must be considered that, although the severity of coronary ischemia is related to the degree of stenosis, this relationship is not always linear. In addition to the degree of obstruction, various factors establish whether a given stenosis induces a myocardial perfusion defect: On the one hand, the existence of collateral circulation or arterial vasospasm can be highlighted and, on the other, a non-significant atherosclerotic plaque can become destabilized and cause a severe or even total arterial obstruction. Furthermore, the phenomenon of «ischemic preconditioning¼, understood. as a phenomenon of endogenous protection by which the myocardium better tolerates a potentially lethal insult when it has previously received sublethal insults, could play a role in the discrepancy between anatomical alterations and functional. For all of the above, to guide revascularization strategies, an evaluation of the functional relevance of coronary stenosis seems useful. Recently, the incorporation of CZT receptors in equipment not specifically dedicated to cardiac imaging (multipurpose or "total body" equipment) has allowed the expansion of its use to the evaluation of other body areas where traditional SPECT-CT equipment was already being used. AIMS: The objective of this report is to describe the diagnostic efficacy and safety of SPECT/CT with direct conversion digital detectors with CZT technology (cadmium, zinc, tellurium) compared to similar equipment equipped with conventional sensors, in the evaluation of myocardial perfusion in patients with ischemic heart disease. As a secondary objective, the use of this equipment in other pathologies and clinical use, in which there is available evidence, will be described. METHODS: After defining the research questions, several bibliographic search strategies were defined for different databases (MEDLINE, EMBASE, CENTRAL and Cochrane library). The searches were mainly aimed at knowing the effectiveness and safety according to the questions asked and the selection of the bibliography were carried out according to different criteria for the two areas of use of the technology: the application to the study of cardiac perfusion and the use in other areas. For the first case, studies that provided the greatest certainty in based on their conclusions were selected; for the second part, a panoramic review was made in order to identify the greatest number of areas of use. The selection, purification and synthesis of the information was carried out by two members of the group and in case of doubt it was solve by consensus. For quality assessment, the AMSTAR-2 tool was used for systematic reviews and the Robins-I tool was used for observational studies. Evidence synthesis was performed using the GRADE methodology with the GRADE-Pro tool. The results and key points were agreed upon by all the authors RESULTS The results were structured in two parts: efficacy and safety results of SPECT/CT CZT in the evaluation of cardiac perfusion and description of other applications. EFFICACY AND SAFETY OF SPECT/CT CZT FOR THE ANALYSIS OF CARDIAC PERFUSION. Question 1: Effectiveness in patients with suspected coronary ischemia. After the literature search, it was possible to identify a systematic review whose objective was to compare the diagnostic performance between SPECT-CZT and SPECT-conventional in patients with coronary artery disease confirmed by angiography. This review was rated as low quality according to AMSTAR-II criteria. The comparison of the diagnostic efficacy between both techniques was performed indirectly, since the authors of the review were unable to identify studies that directly compared both techniques on a sample of patients from the same population. The review focused on the analysis of diagnostic efficacy, measured in terms of sensitivity and specificity: Thus, the estimated sensitivity is 85% [95% CI 79%-89%] for SPECT-Conventional compared to 89% [95% CI 86 %-91%] for SPECT-CZT and the specificity is 66% [95% CI 56%-74%] and 69% [95% CI 61%-75%]. ROC curve analysis shows a slightly larger area under the curve for SPECT-CZT area=0.89 [95% CI 0.86-0.92], with fairly restricted confidence and prediction regions, compared to SPECT-C area=0.83 [CI95% 0.80-0.86]. (Comparison hypothesis test p=0.03). Question 2: Safety in patients with suspected coronary ischemia. As in other diagnostic hybrid imaging studies, the main risks are associated with potential exposure to radiation. An observational study with a control group matched for age, sex and body mass index was identified. It included patients referred to a single institution for the evaluation of a possible coronary artery disease by SPECT, the total dose of radiation received in each of the patients was quantified in the entire diagnostic and treatment process up to 90 days after the indication, including that received in the SPECT, the angiographies, catheterizations and the percutaneous coronary intervention when it was performed. Both, the intervention group (SPECT-CZT) and the control group (SPECTconventional) seemed to follow the same diagnostic and therapeutic routine according to findings and needs indicated by the responsible professionals. The risk of bias of this study was assessed using the Robins-I tool and was classified as serious risk. It should also be considered that this evidence is indirect, since the patients were not evaluated with hybrid equipment, but rather with SPECT equipment not equipped with CT. The main result shown is the difference in dose received between the patients included in the group exposed to SPECT-CZT and those included in the comparison group, estimated at -3.1 mSv [95% CI -4.32; -1.87]. OTHER APPS The search initially allowed the identification of 35 references likely to describe present clinical applications, or closely to be incorporated, of the technology that is the subject of this report. After the selection and filtering of the works finally identified, only 6 originals provided useful information. The most frequently described non-coronary perfusion application is the study of cerebral vascular perfusion, possibly due to the improved resolution and speed of analysis that CZT sensors have provided. Its usefulness for the detection and monitoring of solid lesions of tumor origin or suspected to be so, especially in breast, lymphatic system and bone lesions, has also been described. Finally, the use of the devices object of the report in the analysis and quantification of the ejection fraction of the left ventricle has also been reported. FINDINGS: Currently the use of CZT supposes the updating of an already consolidated technology. The evidence identified to evaluate the benefit of SPECT-CT CZT versus SPECT-CT, although of poor quality and being indirect, allows us to conclude that it could be more effective in the study of ischemic coronary disease. The radiation dose received in patients who undergo SPECT/CT CZT seems to be lower compared to those who undergo conventional SPECT/ CT, although the quality of the evidence has been considered very low, essentially due to the risk of bias and being indirect. The use of this technology for indications other than cardiac is beginning to be defined. Currently, the most frequently described could be the study of cerebral vascular perfusion and the study of solid malignant or suspected malignant lesions.

Evaluation of DNA damage induced by ionizing radiation from myocardial perfusion imaging: a pilot study.

BACKGROUND: As patient exposure to ionizing radiation raises concern about malignancy risks, this study evaluated the effect of ionizing radiation on patients undergoing myocardial perfusion imaging (MPI) using the comet assay, a method for detection of DNA damage. METHODS: Patients without cancer, acute or autoimmune diseases, recent surgery or trauma, were studied. Gated single-photon myocardial perfusion imaging was performed with Tc-99m sestamibi. Peripheral blood was collected before radiotracer injection at rest and 60-90 min after injection. Single-cell gel electrophoresis (comet assay) was performed with blood lymphocytes to detect strand breaks, which determine a "comet tail" of variable size, visually scored by 3 observers in a fluorescence microscope after staining (0: no damage, no tail; 1: small damage; 2: large damage; 3: full damage). A damage index was calculated as a weighted average of the cell scores. RESULTS: Among the 29 individuals included in the analysis, age was 65.3 ± 9.9 years and 18 (62.1%) were male. The injected radiotracer dose was 880.6 ± 229.4 MBq. Most cells (approximately 70%) remained without DNA fragmentation (class 0) after tracer injection. There were nonsignificant increases of classes 1 and 2 of damage. Class 3 was the least frequent both before and after radiotracer injection, but displayed a significant, 44% increase after injection. CONCLUSION: While lymphocytes mostly remained in class 0, an increase in class 3 DNA damage was detected. This may suggest that, despite a probable lack of biologically relevant DNA damage, there is still a need for tracer dose reductions in MPI.

Além da angiografia. Integrando fisiologia e imagem para tomada de decisão em cenário clínico complexo / In addition to angiography. Integrating physiology and imaging for decision making in a complex clinical setting

Apresentação Clínica • Paciente masculino, 59 anos; • Servente de obras; • Antecedentes: HAS, ex-tabagismo, • Fevereiro de 2021: SCASSST ­ atendido em serviço externo; • Optado por estratificação não invasiva. • Câncer de próstata em programação cirúrgica

Handling missing values in machine learning to predict patient-specific risk of adverse cardiac events: Insights from REFINE SPECT registry.

BACKGROUND: Machine learning (ML) models can improve prediction of major adverse cardiovascular events (MACE), but in clinical practice some values may be missing. We evaluated the influence of missing values in ML models for patient-specific prediction of MACE risk. METHODS: We included 20,179 patients from the multicenter REFINE SPECT registry with MACE follow-up data. We evaluated seven methods for handling missing values: 1) removal of variables with missing values (ML-Remove), 2) imputation with median and unique category for continuous and categorical variables, respectively (ML-Traditional), 3) unique category for missing variables (ML-Unique), 4) cluster-based imputation (ML-Cluster), 5) regression-based imputation (ML-Regression), 6) missRanger imputation (ML-MR), and 7) multiple imputation (ML-MICE). We trained ML models with full data and simulated missing values in testing patients. Prediction performance was evaluated using area under the receiver-operating characteristic curve (AUC) and compared with a model without missing values (ML-All), expert visual diagnosis and total perfusion deficit (TPD). RESULTS: During mean follow-up of 4.7 ± 1.5 years, 3,541 patients experienced at least one MACE (3.7% annualized risk). ML-All (reference model-no missing values) had AUC 0.799 for MACE risk prediction. All seven models with missing values had lower AUC (ML-Remove: 0.778, ML-MICE: 0.774, ML-Cluster: 0.771, ML-Traditional: 0.771, ML-Regression: 0.770, ML-MR: 0.766, and ML-Unique: 0.766; p < 0.01 for ML-Remove vs remaining methods). Stress TPD (AUC 0.698) and visual diagnosis (0.681) had the lowest AUCs. CONCLUSION: Missing values reduce the accuracy of ML models when predicting MACE risk. Removing variables with missing values and retraining the model may yield superior patient-level prediction performance.