PET myocardial perfusion imaging: Trends, challenges, and opportunities.

Various non-invasive images are used in clinical practice for the diagnosis and prognostication of chronic coronary syndromes. Notably, quantitative myocardial perfusion imaging (MPI) through positron emission tomography (PET) has seen significant technical advancements and a substantial increase in its use over the past two decades. This progress has generated an unprecedented wealth of clinical information, which, when properly applied, can diagnose and fine-tune the management of patients with different types of ischemic syndromes. This state-of-art review focuses on quantitative PET MPI, its integration into clinical practice, and how it holds up at the eyes of modern cardiac imaging and revascularization clinical trials, along with future perspectives.

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.

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.

Effects of Ivabradine on Myocardial Perfusion in Chronic Angina: A Prospective, Preliminary, Open-Label, Single-Arm Study.

INTRODUCTION: Ivabradine reduces heart rate (HR), episodes of angina, and nitrate consumption, and increases exercise capacity in patients with chronic angina (CA). In this exploratory study, myocardial perfusion scintigraphy (MPS) was used to evaluate changes in the percentage of myocardial ischemia after ivabradine therapy in patients with CA. METHODS: This prospective, open-label, single-arm study included patients with CA receiving maximum tolerated doses of beta blockers, who had a resting HR ≥ 70 bpm and had experienced ischemia according to MPS during an exercise test at baseline. Participants received ivabradine 5 mg twice daily (titrated according to HR) concomitant with beta blockers. A second MPS was performed after 3 months, without interruption of treatment with beta blockers or ivabradine. The primary outcome was change in the percentage of myocardial ischemia from baseline to 3 months. Time to ischemia during the exercise test, the proportion of patients presenting angina during the exercise test, and health status, assessed using the seven-item Seattle Angina Questionnaire-7 (SAQ-7), were also evaluated. RESULTS: Twenty patients (3 females) with a mean (± standard deviation [SD]) age of 62.2 ± 6.5 years were included in the study, of whom 55% had diabetes, 70% had previous myocardial revascularization, and 45% had previous myocardial infarction. The percentage of patients with myocardial ischemia significantly decreased from baseline to 3 months after initiation of treatment with ivabradine (- 2.9%; 95% confidence interval [CI] - 0.3 to - 5.5; p = 0.031). Mean time to appearance of ischemia increased from 403 ± 176 s at baseline to 466 ± 136 s at 3 months after initiation of ivabradine (Δ62 s; 95% CI 18-106 s; p = 0.008), and the proportion of patients experiencing angina during the exercise test decreased from 40% at baseline to 5% also at 3 months (p = 0.016). Mean resting HR decreased from 76 ± 7 bpm at baseline to 55 ± 8 bpm at 3 months (p < 0.001). The mean SAQ-7 summary score improved from 69 ± 21 at baseline to 83 ± 12 at 3 months (p = 0.001). No serious adverse effects were reported. CONCLUSION: Ivabradine added to beta blockers was associated with a reduction in detectable myocardial ischemia by MPS in patients with CA. Infographic available for this article. TRIAL REGISTRATION: The trial has been retrospectively registered with the Brazilian Registry of Clinical Trials (REBEC) under the following number RBR-5fysqrh (date of registration: 30 November 2023).

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)

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.

Associação de Nível de Renda e Doença Isquêmica do Coração: Papel Potencial da Caminhabilidade / Association of Income Level and Ischemic Heart Disease: Potential Role of Walkability

Resumo Fundamento O nível socioeconômico tem sido associado à doença isquêmica do coração (DIC). Bairros de alta renda podem expor os indivíduos a um ambiente construído que promova caminhadas para atividades diárias (caminhabilidade). Faltam dados sobre a associação entre renda e DIC em países de renda média. Também é incerto se a caminhabilidade medeia essa associação. Objetivos Investigar se a renda está associada à DIC em um país de renda média e se a caminhabilidade dos bairros medeia a associação entre renda e DIC. Métodos O presente estudo transversal avaliou 44.589 pacientes encaminhados para imagem de perfusão miocárdica (SPECT-MPI). A renda e a caminhabilidade foram derivadas do setor censitário residencial dos participantes. A pontuação quantitativa da caminhabilidade combinou as seguintes 4 variáveis: conectividade viária, densidade residencial, densidade comercial e uso misto do solo. A DIC foi definida pela presença de perfusão miocárdica anormal durante um estudo SPECT-MPI. Utilizamos modelos ajustados com efeitos mistos para avaliar a associação entre nível de renda e DIC e realizamos uma análise de mediação para medir o percentual da associação entre renda e DIC mediada pela caminhabilidade. Consideramos valores de p abaixo de 0,01 como estatisticamente significativos. Resultados Dos 26.415 participantes, aqueles que residiam no setor censitário do tercil de menor renda eram mais fisicamente inativos (79,1% versus 75,8% versus 72,7%) quando comparados aos setores censitários do tercil de maior renda (p < 0,001). A renda foi associada à DIC (odds ratio: 0,91 [intervalo de confiança de 95%: 0,87 a 0,96] para cada aumento de 1000,00 dólares internacionais na renda), para homens e mulheres igualmente (p para interação = 0,47). Os setores censitários com maior renda estiveram associados a uma melhor caminhabilidade (p < 0,001); no entanto, a caminhabilidade não mediou a associação entre renda e DIC (porcentagem mediada = −0,3%). Conclusões A renda foi independentemente associada a maior prevalência de DIC em um país de renda média, independentemente de gênero. Embora a caminhabilidade tenha sido associada à renda do setor censitário, ela não mediou a associação entre renda e DIC.

Abstract Background Socioeconomic status has been linked to ischemic heart disease (IHD). High-income neighborhoods may expose individuals to a walking-promoting built environment for daily activities (walkability). Data from the association between income and IHD is lacking in middle-income countries. It is also uncertain whether walkability mediates this association. Objectives To investigate whether income is associated with IHD in a middle-income country and whether neighborhood walkability mediates the income-IHD association. Methods This cross-sectional study evaluated 44,589 patients referred for myocardial perfusion imaging (SPECT-MPI). Income and walkability were derived from participants' residential census tract. Walkability quantitative score combined 4 variables: street connectivity, residential density, commercial density, and mixed land use. IHD was defined by abnormal myocardial perfusion during a SPECT-MPI study. We used adjusted mixed effects models to evaluate the association between income level and IHD, and we performed a mediation analysis to measure the percentage of the income-IHD association mediated by walkability. We considered p values below 0.01 as statistically significant. Results From 26,415 participants, those living in the lowest-income tertile census tract were more physically inactive (79.1% versus 75.8% versus 72.7%) when compared to higher-income tertile census tracts (p < 0.001). Income was associated with IHD (odds ratio: 0.91 [95% confidence interval: 0.87 to 0.96] for each 1,000.00 international dollars increase in income) for both men and women equally (p for interaction = 0.47). Census tracts with a higher income were associated with better walkability (p < 0.001); however, walkability did not mediate the income-IHD association (percent mediated = −0.3%). Conclusions Income was independently associated with higher prevalence of IHD in a middle-income country irrespective of gender. Although walkability was associated with census tract income, it did not mediate the income-IHD association.

Relação entre a Relação Fibrinogênio/Albumina e a Perfusão Microvascular em Pacientes Submetidos à Intervenção Coronária Percutânea Primária para Infarto do Miocárdio com Elevação do Segmento ST: Um Estudo Prospectivo / Relationship between the Fibrinogen/Albumin Ratio and Microvascular Perfusion in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Elevated Myocardial Infarction: A Prospective Study

Resumo Fundamento A contagem corrigida de quadros TIMI (CTFC), o grau de blush miocárdico (MBG) e a resolução do segmento ST (STR) são parâmetros utilizados para avaliar a reperfusão em nível microvascular em pacientes submetidos à intervenção coronária percutânea primária (ICPp). A relação fibrinogênio/albumina (FAR) tem sido associada a eventos trombóticos em pacientes com infarto do miocárdio com elevação do segmento ST (IAMCSST) e insuficiência venosa crônica. Objetivos Investigar a relação do FAR com CTFC, MBG e STR.Métodos: O estudo incluiu 167 pacientes consecutivos que foram submetidos a ICPp com sucesso para IAMCSST e alcançaram fluxo TIMI-3. Os casos foram divididos em dois grupos, FAR alto (> 0,0765) e FAR baixo (≤ 0,0765), de acordo com o valor de corte desse parâmetro na análise característica do operador do receptor (ROC). STR, CTFC e MBG foram utilizados para avaliar a reperfusão miocárdica. Valores de p<0,05 foram considerados estatisticamente significativos. Resultados O valor CTFC, escore SYNTAX, relação neutrófilos/linfócitos, lipoproteína de baixa densidade, glicose e pico de cTnT foram significativamente maiores, enquanto STR, MBG e FEVE foram menores no grupo FAR alto. A análise de correlação de Spearman revelou relação significativa entre FAR e STR (r=-0,666, p<0,001), MBG (-0,523, p<0,001) e CTFC (r=0,731, p≤0,001). De acordo com a análise de regressão logística, FAR, glicose, pico de cTnT e dor até o tempo de Balão foram os preditores independentes mais importantes de MBG 0/1, CTFC>28 e STR<50%). A análise ROC revelou que o ponto de corte o valor de FAR≥0,0765 foi preditor de STR incompleto com sensibilidade de 71,9% e especificidade de 69,8%, MBG0/1 com sensibilidade de 72,6% e especificidade de 68,6%, e CTFC>28 com sensibilidade de 76% e uma especificidade de 65,8%. Conclusões A FAR é um importante preditor independente de perfusão microvascular em pacientes submetidos a ICPp por IAMCSST.

Abstract Background Correct TIMI frame count (CTFC), myocardial blush grade (MBG), and ST-segment resolution (STR) are parameters used to evaluate reperfusion at the microvascular level in patients that have undergone primary percutaneous coronary intervention (pPCI). Fibrinogen-to-albumin ratio (FAR) has been associated with thrombotic events in patients with ST-elevation myocardial infarction (STEMI) and chronic venous insufficiency. Objectives To investigate the relationship of FAR with CTFC, MBG, and STR. Methods: The study included 167 consecutive patients who underwent successful pPCI for STEMI and achieved TIMI-3 flow. The cases were divided into two groups, high (>0.0765) and low FAR (≤0.0765), according to the cut-off value of this parameter in the receiver operator characteristic analysis (ROC). STR, CTFC, and MBG were used to evaluate myocardial reperfusion. P values<0.05 were considered statistically significant. Results CTFC value, SYNTAX score, neutrophil/lymphocyte ratio, low-density lipoprotein, glucose, and peak cTnT were significantly higher, whereas STR, MBG, and LVEF were lower in the high FAR group. Spearman's correlation analysis revealed a significant relationship between the FAR and STR (r=-0.666, p<0.001), MBG (-0.523, p<0.001), and CTFC (r=0.731, p≤0.001). According to the logistic regression analysis, FAR, glucose, peak cTnT, and pain to balloon time were the most important independent predictors of MBG 0/1, CTFC>28, and STR<50%).ROC analysis revealed that the cut-off value of FAR≥0.0765 was a predictor of incomplete STR with a sensitivity of 71.9 % and a specificity of 69.8 %, MBG0/1 with a sensitivity of 72.6 % and a specificity of 68.6 %, and CTFC >28 with a sensitivity of 76 % and a specificity of 65.8 %. Conclusions FAR is an important independent predictor of microvascular perfusion in patients undergoing pPCI for STEMI.

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.

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.

Effects of Ticagrelor and Clopidogrel on Coronary Microcirculation in Patients with Acute Myocardial Infarction.

INTRODUCTION: Clopidogrel has been demonstrated to be effective in improving coronary microcirculation (CM) among patients with ST-elevation myocardial infarction (STEMI) treated with fibrinolytics. Ticagrelor is a more potent adenosine diphosphate (ADP) receptor blocker proven to be superior to clopidogrel among patients with acute coronary syndromes. The present study aimed to compare the effects of ticagrelor and clopidogrel on CM in patients with STEMI treated with fibrinolytics. METHODS: The present study prospectively included 48 patients participating in the TREAT trial, which randomly assigned patients with STEMI undergoing fibrinolysis to ticagrelor versus clopidogrel. The primary endpoint of this study was the evaluation of the CM using the global myocardial perfusion score index (global MPSI) obtained by myocardial contrast echocardiography (MCE). Platelet aggregation to ADP was evaluated by Multiplate® and expressed as area under the curve (AUC). RESULTS: The global MPSI demonstrated no differences between the groups [mean 1.4 (1.2-1.5) in the ticagrelor group and 1.2 (1.2-1.5) in the clopidogrel group (p = 0.41)]. Platelet aggregability was lower in the ticagrelor group (18.1 ± 9.7 AUC), compared to the clopidogrel group (26.1 ± 12.5 AUC, p = 0.01). CONCLUSION: We found no improvement in coronary microcirculation with ticagrelor compared to clopidogrel among patients with STEMI treated with fibrinolytics, despite the fact that platelet aggregation to ADP was lower with ticagrelor. CLINICAL TRIALS REGISTRATION: NCT03104062.

Comparison between Bruce and ramp protocols for exercise testing in the diagnosis of myocardial ischemia

BACKGROUND: Exercise tests are an important tool in the investigation of myocardial ischemia. The ramp protocol has gained increasing importance in clinical practice because of the possibility of individualizing its exercise intensity. OBJECTIVE: To assess and compare the sensitivity, specificity, and accuracy of Bruce and ramp protocols for exercise testing in the diagnosis of myocardial ischemia considering myocardial perfusion scintigraphy as the reference standard. Secondary objectives included the assessment of hemodynamic profiles, functional capacity, and the incidence of arrhythmias in each of the protocols. METHODS: Participants underwent exercise testing using the ramp and Bruce protocols, and the tests' diagnostic power was assessed. For testing the difference between data provided by both protocols, we used a paired Student's t-test or Wilcoxon test, depending on the assumption of data normality. The level of significance adopted for all tests was 5%. RESULTS: The ramp protocol showed sensitivity, specificity, and accuracy values of 55.6%, 82.4%, and 76.7%, respectively, whereas the Bruce protocol had results of 77.8%, 64.7%, and 67.4%, respectively. The maximum heart rate and double product at peak exercise were significantly higher in the Bruce protocol (p = 0.043 and p = 0.040, respectively). No differences were observed between the incidence of arrhythmias in both protocols. CONCLUSION: The Bruce protocol presented higher sensitivity for detecting ischemia on the exercise test, while the ramp protocol presented higher specificity and accuracy.

[Prediction of significant coronary lesions by SPECT myocardial perfusion. Results from a national reference hospital in Lima-Peru]. / Predicción de lesiones coronarias significativas mediante perfusión miocárdica con SPECT. Resultados de un centro de referencia nacional en Lima-Perú.

Objective: To determine the discriminative capacity of myocardial perfusion with single photon emission tomography (SPECT) to predict coronary obstructions by coronary angiography. To determine mortality and major cardiovascular events at follow-up. Materials and methods: . Retrospective observational study with clinical follow-up in patients undergoing SPECT and then coronary angiography. We excluded patients with myocardial infarction and percutaneous and/or surgical revascularization in the previous 6 months. Results: 105 cases were included in the study. The most commonly used SPECT protocol was pharmacological (70%). Patients with perfusion defect ≥10% of total ventricular mass (TVM) had significant coronary lesions (SCL) in 88% of cases (sensitivity 87.5% and specificity 83%). On the other hand, having ischemia ≥10% of the TVM was associated with 80% SCL (sensitivity: 72%, specificity: 65%). Clinical follow-up at 48 months evidenced that a perfusion defect ≥ 10% was predictive of major cardiovascular events (MACE) in both univariate (HR=5.3; 95%CI 1.2 - 22.2; p=0.022) and multivariate (HR= 6.1; 95%CI 1.3 - 26.9; p= 0.017) analyses. Conclusions: . Having a perfusion defect ≥10% of the MVT in the SPECT study predicted with high probability and sensitivity the existence of SCL (>80%); moreover, this group had higher MACE at follow-up.

Machine Learning Algorithms to Distinguish Myocardial Perfusion SPECT Polar Maps.

Myocardial perfusion imaging (MPI) plays an important role in patients with suspected and documented coronary artery disease (CAD). Machine Learning (ML) algorithms have been developed for many medical applications with excellent performance. This study used ML algorithms to discern normal and abnormal gated Single Photon Emission Computed Tomography (SPECT) images. We analyzed one thousand and seven polar maps from a database of patients referred to a university hospital for clinically indicated MPI between January 2016 and December 2018. These studies were reported and evaluated by two different expert readers. The image features were extracted from a specific type of polar map segmentation based on horizontal and vertical slices. A senior expert reading was the comparator (gold standard). We used cross-validation to divide the dataset into training and testing subsets, using data augmentation in the training set, and evaluated 04 ML models. All models had accuracy >90% and area under the receiver operating characteristics curve (AUC) >0.80 except for Adaptive Boosting (AUC = 0.77), while all precision and sensitivity obtained were >96 and 92%, respectively. Random Forest had the best performance (AUC: 0.853; accuracy: 0,938; precision: 0.968; sensitivity: 0.963). ML algorithms performed very well in image classification. These models were capable of distinguishing polar maps remarkably into normal and abnormal.

Correlación de sincronía de la contracción del ventrículo izquierdo con función sisto-diastólica, masa y excentricidad en diversas afecciones cardíacas mediante un software comercial dedicado de SPECT gatillado / Gated Spect evaluation of ventricular systolic synchrony: correlation with ventricular mass and excentricity in different forms of cardiac disease

INTRODUCCIÓN: Actualmente, hay nuevas herramientas de software disponibles para medir la sincronía de la contracción intraventricular izquierda mediante SPECT de perfusión miocárdica. Esta técnica permite identificar anomalías de la conducción, apoyar la terapia de resincronización en insuficiencia cardíaca refractaria e incluso la detección precoz de isquemia. OBJETIVO: Conocer la correlación de la sincronía de contracción con otros parámetros de disfunción sisto-diastólica ventricular izquierda. MÉTODO: Estudiamos 135 pacientes remitidos para pesquisa o evaluación de enfermedad coronaria conocida mediante SPECT gatillado. La evaluación de la interpretación inicial con programas QPS/QGS® visual y cuantitativo se efectuó a 50 casos con defectos de perfusión transitoria de diversos tamaños (isquemia), 25 de tipo fijo o mixto (infarto) y 60 sin ellos (normal). Los volúmenes telesistólicos oscilaron entre 26 y 458 mL. Se excluyeron casos con arritmias, anomalías de conducción y artefactos (actividad o movimiento extracardiaco). Los SPECT se procesaron retrospectivamente utilizando el programa Emory Synctool®. Del histograma de sincronía de la contracción, el ancho de banda (BW) y la desviación estándar (SD) se correlacionaron con la fracción de eyección (FEVI), volúmenes y excentricidades sistólico / diastólico, masa ventricular izquierda, tasa máxima de llenado (PFR) y tiempo al máximo de llenado (TPFR). RESULTADOS: Los BW y SD del histograma de fase de contracción fueron mayores en el grupo con defectos fijos y mixtos en comparación con los con perfusión normal. Las correlaciones en reposo y post estrés (Spearman) entre SD y BW con FEVI, volúmenes, excentricidad y masa fueron significativas (p <0,0002) salvo TPFR que no fue significativa. CONCLUSIÓN: La sincronía de contracción intraventricular sistólica izquierda medida con SPECT se correlaciona excelentemente con los parámetros funcionales sistólicos y diastólicos, así como con masa y excentricidad en diversas condiciones y tamaños cardíacos.

INTRODUCTION: New software tools are available to measure left intraventricular contraction synchrony by myocardial perfusion SPECT. This technique allows identification of conduction abnormalities, support resynchronization therapy in refractory heart failure and even allows early detection of myocardial ischemia. OBJECTIVE: To determine the correlation of systolic synchrony with other parameters of left ventricular systolic-diastolic dysfunction. METHODS: We studied 135 patients referred for screening or known coronary artery disease evaluation by triggered SPECT. Evaluation of the initial interpretation with visual and quantitative QPS/QGS® programs was performed in 50 patients with transient perfusion defects of various sizes (ischemia), 25 of fixed or mixed type (infarction) and 60 without abnormalities. Telesystolic volumes ranged from 26 to 458 mL. Cases with arrhythmias, conduction abnormalities and artifacts (extracardiac activity or motion) were excluded. SPECT scans were retrospectively processed using the Emory Synctool® software. Histograms of systolic contraction synchrony bandwidth (BW) and standard deviation (SD) were correlated with ejection fraction (LVEF), systolic/diastolic volumes and eccentricities, left ventricular mass, peak filling rate (PFR) and time to maximum filling (TPFR). RESULTS: BW and SD of the contraction pase histogram were higher in the fixed and mixed defect group compared to studies showing normal perfusion. Spearman correlations at rest and poststress between SD and BW with LVEF, volumes, eccentricity and mass were all significant (p<0.0002) except for TPFR. CONCLUSION: Left systolic intraventricular contraction synchrony measured with SPECT presents an excellent correlation with systolic and diastolic functional parameters, as well as with mass and eccentricity in various cardiac conditions and ventricular dimensions.

Machine Learning Algorithms to Detect Sex in Myocardial Perfusion Imaging.

Myocardial perfusion imaging (MPI) is an essential tool used to diagnose and manage patients with suspected or known coronary artery disease. Additionally, the General Data Protection Regulation (GDPR) represents a milestone about individuals' data security concerns. On the other hand, Machine Learning (ML) has had several applications in the most diverse knowledge areas. It is conceived as a technology with huge potential to revolutionize health care. In this context, we developed ML models to evaluate their ability to distinguish an individual's sex from MPI assessment. We used 260 polar maps (140 men/120 women) to train ML algorithms from a database of patients referred to a university hospital for clinically indicated MPI from January 2016 to December 2018. We tested 07 different ML models, namely, Classification and Regression Tree (CART), Naive Bayes (NB), K-Nearest Neighbors (KNN), Support Vector Machine (SVM), Adaptive Boosting (AB), Random Forests (RF) and, Gradient Boosting (GB). We used a cross-validation strategy. Our work demonstrated that ML algorithms could perform well in assessing the sex of patients undergoing myocardial scintigraphy exams. All the models had accuracy greater than 82%. However, only SVM achieved 90%. KNN, RF, AB, GB had, respectively, 88, 86, 85, 83%. Accuracy standard deviation was lower in KNN, AB, and RF (0.06). SVM and RF had had the best area under the receiver operating characteristic curve (0.93), followed by GB (0.92), KNN (0.91), AB, and NB (0.9). SVM and AB achieved the best precision. Our results bring some challenges regarding the autonomy of patients who wish to keep sex information confidential and certainly add greater complexity to the debate about what data should be considered sensitive to the light of the GDPR.