Diastolic function assessment with four-dimensional flow cardiovascular magnetic resonance using automatic deep learning E/A ratio analysis.

BACKGROUND: Diastolic left ventricular (LV) dysfunction is a powerful contributor to the symptoms and prognosis of patients with heart failure. In patients with depressed LV systolic function, the E/A ratio, the ratio between the peak early (E) and the peak late (A) transmitral flow velocity, is the first step to defining the grade of diastolic dysfunction. Doppler echocardiography (echo) is the preferred imaging technique for diastolic function assessment, while cardiovascular magnetic resonance (CMR) is less established as a method. Previous four-dimensional (4D) Flow-based studies have looked at the E/A ratio proximal to the mitral valve, requiring manual interaction. In this study, we compare an automated, deep learning-based and two semi-automated approaches for 4D Flow CMR-based E/A ratio assessment to conventional, gold-standard echo-based methods. METHODS: Ninety-seven subjects with chronic ischemic heart disease underwent a cardiac echo followed by CMR investigation. 4D Flow-based E/A ratio values were computed using three different approaches; two semi-automated, assessing the E/A ratio by measuring the inflow velocity (MVvel) and the inflow volume (MVflow) at the mitral valve plane, and one fully automated, creating a full LV segmentation using a deep learning-based method with which the E/A ratio could be assessed without constraint to the mitral plane (LVvel). RESULTS: MVvel, MVflow, and LVvel E/A ratios were strongly associated with echocardiographically derived E/A ratio (R2 = 0.60, 0.58, 0.72). LVvel peak E and A showed moderate association to Echo peak E and A, while MVvel values were weakly associated. MVvel and MVflow EA ratios were very strongly associated with LVvel (R2 = 0.84, 0.86). MVvel peak E was moderately associated with LVvel, while peak A showed a strong association (R2 = 0.26, 0.57). CONCLUSION: Peak E, peak A, and E/A ratio are integral to the assessment of diastolic dysfunction and may expand the utility of CMR studies in patients with cardiovascular disease. While underestimation of absolute peak E and A velocities was noted, the E/A ratio measured with all three 4D Flow methods was strongly associated with the gold standard Doppler echocardiography. The automatic, deep learning-based method performed best, with the most favorable runtime of ∼40 seconds. As both semi-automatic methods associated very strongly to LVvel, they could be employed as an alternative for estimation of E/A ratio.

Comprehensive Angiography-Derived Functional Assessment of Epicardial and Microvascular Coronary Disease. Correlation With Non-invasive Myocardial Stress Imaging.

Coronary angiography (CA) is poorly correlated with non-invasive myocardial stress imaging (NSI) and myocardial ischemia is often observed in patients with unobstructed coronary arteries. Moreover, the diagnostic performance of combined epicardial and microcirculatory angiography-derived physiological assessment and its correlation with NSI remains unknown. A total of 917 coronary vessels in 319 patients who underwent both CA and NSI were included in this multicenter observational retrospective analysis. Quantitative flow ratio (QFR) and angiography-derived index of microcirculatory resistance (IMRangio) analyses were performed to estimate coronary epicardial and microcirculatory function respectively. NSI demonstrated evidence of myocardial ischemia in 76% of the cases. IMRangio (36 [22 to 50] vs 29 [21 to 41], p <0.001) was significantly higher and QFR (0.92 [0.78 to 0.99] vs 0.97 [0.91 to 0.99], p <0.001) was significantly lower in vessels subtending ischemic territories. Overall, the diagnostic accuracy of QFR was moderate (area under the curve of receiver operating characteristic [AUCROC] 0.632 [95% confidence interval [CI] 0.589 to 0.674], p <0.0001) but it was higher in patients with normal microcirculatory function (AUCROC = 0.726 [95% CI 0.669 to 0.784], p <0.0001, p Value for AUCROC comparison = 0.009). Combined QFR/IMRangio assessment provided incremental diagnostic performance compared with the evaluation of epicardial or microcirculatory districts in isolation (p Value for AUC comparison <0.0001) and it was able to identify the predominant mechanism of myocardial ischemia in 77% of the patients with positive NSI. Our study suggests the value of a combined angiography-derived assessment of epicardial and microvascular function for the definition of the predominant mechanism of myocardial ischemia in patients with suspected coronary artery disease.

Opportunistic assessment of ischemic heart disease risk using abdominopelvic computed tomography and medical record data: a multimodal explainable artificial intelligence approach.

Current risk scores using clinical risk factors for predicting ischemic heart disease (IHD) events-the leading cause of global mortality-have known limitations and may be improved by imaging biomarkers. While body composition (BC) imaging biomarkers derived from abdominopelvic computed tomography (CT) correlate with IHD risk, they are impractical to measure manually. Here, in a retrospective cohort of 8139 contrast-enhanced abdominopelvic CT examinations undergoing up to 5 years of follow-up, we developed multimodal opportunistic risk assessment models for IHD by automatically extracting BC features from abdominal CT images and integrating these with features from each patient's electronic medical record (EMR). Our predictive methods match and, in some cases, outperform clinical risk scores currently used in IHD risk assessment. We provide clinical interpretability of our model using a new method of determining tissue-level contributions from CT along with weightings of EMR features contributing to IHD risk. We conclude that such a multimodal approach, which automatically integrates BC biomarkers and EMR data, can enhance IHD risk assessment and aid primary prevention efforts for IHD. To further promote research, we release the Opportunistic L3 Ischemic heart disease (OL3I) dataset, the first public multimodal dataset for opportunistic CT prediction of IHD.

Cardiac magnetic resonance imaging for myocardial viability assessment: Optimizing surgical revascularization in ischemic heart disease.

BACKGROUND: Patients with poor ejection fraction undergoing coronary artery bypass grafting carry higher operative risk and have poor long-term survival. Cardiac magnetic resonance is a useful modality to assess viability which can identify patients likely to benefit most from revascularization. In this study, we aimed to assess the outcome in patients selected for surgical revascularization by cardiac magnetic resonance imaging and identify predictors associated with poor outcomes. METHODS: The study included patients with severely impaired left ventricular function but with at least six viable segments. Patients requiring emergency surgery, undergoing combined procedures, or where cardiopulmonary bypass was required were excluded. Cardiac magnetic resonance was carried out both preoperatively and at six months postoperatively by the same radiologist in all cases. Late gadolinium enhancement was used for the evaluation of myocardial viability. RESULTS: Amongst a total of 493 segments studied, there were 89 (18.1%) non-viable, 117 (23.7%) hibernating and 287 (58.2%) viable segments. At six months, the number of non-viable segments changed from 89 (18.1%) to 97 (19.7%), with an increase in viable segments from 287 (58.2%) to 374 (75.8%) and a corresponding reduction of hibernating segments from 117 (23.7%) to 22 (4.5%). There was improvement in ejection fraction from 28 ± 5.54 to 37 ± 5.86 (p < 0.0001) in the entire cohort at six months. Overall mortality was 1 (3.2%). Preoperative left ventricular end-systolic volume had the strongest negative correlation with post-operative ejection fraction. CONCLUSION: Cardiac magnetic resonance aided revascularization is associated with low mortality. Preoperative left ventricular end-systolic volume is an important determinant of postoperative ejection fraction.

The impact of viability assessment using cardiac MRI and echocardiogram on the outcome of revascularization in patients with multi-vessels coronary artery disease and moderate to severe ischemic cardiomyopathy.

OBJECTIVES: To investigate the influence of viability assessment in the management of patients with ischemic cardiomyopathy (ICM). METHODS: This retrospective cohort study included all patients with ICM with moderate to severely reduced left ventricular ejection fraction (LVEF) who underwent viability assessment using cardiac magnetic resonance imaging (MRI) and echocardiogram as modalities of imaging. In addition, LVEF, modality of choice, and treatment plans were all extracted as main variables from the electronic database. One hundred 6 patients who met the inclusion criteria from December 2014 to December 2019 were included. RESULTS: Posttreatment LVEF improved by 5% in the viable group compared to the nonviable group (p=0.016). Regardless of the treatment received, 6 (8.8%) patients in the viable group died due to cardiac causes after an 18-month follow-up period; in contrast, 7 (18.4%) patients died due to cardiac causes in the nonviable group. However, despite that difference, this was not statistically significant (p=0.153). Medical therapy alone was observed in 32 (84.2%) patients in the nonviable group compared to 32 (47.1%) in the viable group (p<0.001). Although the reduction in hospitalization for cardiac reasons was not statistically significant, the viable arm had 50% fewer hospitalizations than the nonviable arm (p=0.051). CONCLUSION: Patients with viable myocardium had better outcomes in which LVEF significantly improved posttreatment. Additionally, there was a reduction in the number of hospitalizations for cardiac reasons in the viable group compared to the nonviable group, even though the difference was not statistically significant. However, further studies with a larger number of patients are needed to determine a definite conclusion.

Comprehensive Assessment of Myocardial Ischemia Mechanisms in the Catheterization Laboratory: Design and Rationale of the Advanced Invasive Diagnosis Strategy for Patients with Stable Coronary Syndromes Undergoing Coronary ANGIOgraphy - the AID-ANGIO Study.

BACKGROUND: The diagnostic yield of invasive coronary angiography (ICA) to identify obstructive coronary artery disease in the context of chronic coronary syndromes (CCS) is very low. Furthermore, myocardial ischemia may have a non-obstructive origin, which cannot be detected by ICA. METHODS: AID-ANGIO is an observational, prospective, single-cohort, multicenter study, intended to evaluate the diagnostic yield of adopting a hierarchical strategy to assess obstructive and non-obstructive causes of myocardial ischemia in an all-comers population of patients with CCS at the time of ICA. The primary endpoint will investigate the additional diagnostic value of such strategy over angiography alone regarding the identification of ischemia-generating mechanisms. SUMMARY: An estimated sample of consecutive 260 patients with CCS referred by their clinicians to ICA, will be enrolled. In a stepwise manner, a conventional ICA will be performed as the initial diagnostic tool. Those patients with severe-grade stenosis will not undergo further assessment and an obstructive origin for myocardial ischemia will be assumed. Subsequently, the remainder with intermediate-grade stenosis will be assessed with pressure guidewires. Those with a negative result from physiological evaluation and those without epicardial coronary stenosis will be further studied for ischemia of non-obstructive origin, including microvascular dysfunction and vasomotor disorders. The study will be conducted in two steps. Firstly, ICA images will be displayed to patient's referring clinicians, who will be asked to identify the existent epicardial stenosis, their angiographic severity and probable physiological relevance, together with a tentative therapeutic approach. Then, the diagnostic algorithm will continue to be applied and, considering the whole gathered information, a definite therapeutic plan will be consensually established by the interventional cardiologist and patient's referring clinicians. CONCLUSION: The AID-ANGIO study will assess the additional diagnostic yield of a hierarchical strategy over ICA alone to identify ischemia-generating mechanisms in patients with CCS and its impact on therapeutic approach. Positive results of the study might support a streamlined invasive diagnostic process for patients with CCS.

A Novel Experimental Rat Model for the In Vivo Assessment of Myocardial Ischemia Based on Single Photon Emission Computed Tomography.

BACKGROUND/AIM: Myocardial infarction, an acute medical situation with a high mortality rate worldwide, has been extensively studied in modern cardiovascular research, using different experimental models. However, a deep understanding of myocardial activity loss has not been fully investigated. We have developed a novel experimental rat model for noninvasive assessment of myocardial ischemia based on single photon emission computed tomography (SPECT/CT), in order to further understand and evaluate myocardial activity before and after surgical induction of myocardial ischemia. MATERIALS AND METHODS: Thirty adult female Wistar rats underwent open thoracotomy with (n=20) or without (n=10) surgical ligation of the left anterior descending coronary artery (LAD). The myocardial ischemia was confirmed with ECG and myocardial viability was evaluated via SPECT/CT at 7 days before as well as at 7 and 14 days post-surgery, after which animals were sacrificed and myocardial ischemic injury was further assessed histologically. RESULTS: All animals were evaluated with anatomical and functional criteria based on the SPECT/CT imaging results. A successful surgical technique causing ischemia and loss of myocardial function in all animals undergoing a LAD ligation was established. Furthermore, evaluation of the viable myocardium with SPECT/CT confirmed the reduction of functional myocardial cells of the left ventricle post-infarction, which was also documented histologically. CONCLUSION: Using our technique, the validity of this animal model to induce and evaluate myocardial ischemia was demonstrated. Our choice to apply SPECT-CT qualitative and quantitative evaluation of myocardial function leads to a new approach in experimentation with an anticipated significant impact in the ongoing cardiovascular laboratory research.

Quantitative Assessment of Myocardial Ischemia With Positron Emission Tomography.

Recent advances in positron emission tomography (PET) technology and reconstruction techniques have now made quantitative assessment using cardiac PET readily available in most cardiac PET imaging centers. Multiple PET myocardial perfusion imaging (MPI) radiopharmaceuticals are available for quantitative examination of myocardial ischemia, with each having distinct convenience and accuracy profile. Important properties of these radiopharmaceuticals ( 15 O-water, 13 N-ammonia, 82 Rb, 11 C-acetate, and 18 F-flurpiridaz) including radionuclide half-life, mean positron range in tissue, and the relationship between kinetic parameters and myocardial blood flow (MBF) are presented. Absolute quantification of MBF requires PET MPI to be performed with protocols that allow the generation of dynamic multiframes of reconstructed data. Using a tissue compartment model, the rate constant that governs the rate of PET MPI radiopharmaceutical extraction from the blood plasma to myocardial tissue is calculated. Then, this rate constant ( K1 ) is converted to MBF using an established extraction formula for each radiopharmaceutical. As most of the modern PET scanners acquire the data only in list mode, techniques of processing the list-mode data into dynamic multiframes are also reviewed. Finally, the impact of modern PET technologies such as PET/CT, PET/MR, total-body PET, machine learning/deep learning on comprehensive and quantitative assessment of myocardial ischemia is briefly described in this review.

Angiography-derived assessment of coronary microcirculatory resistance in patients with suspected myocardial ischaemia and non-obstructive coronary arteries.

BACKGROUND: Myocardial ischaemia with non-obstructive coronary arteries (INOCA) represents a challenging and frequent, but largely underdiagnosed, condition. AIMS: We aimed to investigate the feasibility and diagnostic value of angiography-derived coronary microcirculatory resistance in patients with INOCA syndrome. METHODS: This is an investigator-driven, prospective and blinded study. The diagnostic yield of angiography-derived index of coronary microcirculatory resistance (angio-IMR) was investigated against thermodilution-derived IMR (thermo-IMR) in patients with clinically indicated coronary angiography due to suspected myocardial ischaemia and angiographically normal or non-obstructive coronary arteries. The angio-IMR was derived from resting angiograms (contrast-flow angio-IMR [cAngio-IMR]) by an expert analyst blinded to the thermo-IMR. An independent, blinded, physiology core laboratory analysed the raw intracoronary physiology data and provided the final thermo-IMR values. RESULTS: A total of 104 patients (108 coronary vessels) were analysed after fulfilling predefined inclusion criteria. Most patients were female (67%). Obstructive epicardial disease was angiographically (percent diameter stenosis <50%) and physiologically (fractional flow reserve>0.80) ruled out in all cases. Median thermo-IMR and cAngio-IMR were 16.6 (12.7, 23.0) and 16.8 (12.8, 23.1) units, respectively (median difference -0.31, 95% confidence interval: -1.53 to 1.00; p=0.654). cAngio-IMR showed good correlation (Pearson coefficient 0.76; p<0.001), agreement (mean bias 0.4), discriminatory power (area under the curve from the receiver operator characteristics 0.865; p<0.001) and accuracy (85%), compared to thermo-IMR (≥25 U). CONCLUSIONS: Evaluating coronary microcirculatory resistance in patients with INOCA syndrome using cAngio-IMR is feasible and accurate. By circumventing the need of coronary instrumentation and hyperaemic drugs, this method may facilitate the assessment of coronary microcirculatory resistance in patients with suspected INOCA. CLINICALTRIALS: gov: NCT04827498.

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.

Low-dose dobutamine stress gated blood pool SPECT assessment of left ventricular contractile reserve in ischemic cardiomyopathy: a feasibility study.

PURPOSE: The purpose of the present study was to evaluate the feasibility of gated blood pool single-photon emission computed tomography (GBPS) with low-dose dobutamine (LDD) stress test, performed on a single-photon emission computed tomography (SPECT) camera equipped with cadmium-zinc-telluride (CZT) solid-state detectors, in assessing of left ventricle (LV) contractile reserve in patients with ischemic cardiomyopathy (ICM). METHODS: A total of 52 patients (age 59 ± 7.2 years, 47 men and 5 women) with ICM and a control group of 10 patients without obstructive coronary artery lesion underwent GBPS and transthoracic echocardiography (TTE) at rest and during LDD stress test (5, 10, 15 µg/kg/min). The duration of each GBPS step was 5 min. Stress-induced changes in LV ejection fraction (ΔLVEF), peak ejection rate, LV volumes, and mechanical dyssynchrony (phase histogram standard deviation, phase histogram bandwidth and entropy) obtained with GBPS were estimated. RESULTS: All GBPS indices except end-diastolic volume showed significant dynamics during stress test in both groups. The majority of parameters in ICM patients showed significant changes at a dobutamine dose of 10 µg/kg/min as compared to the rest study. Seventeen percent of ICM patients, but none from the control group, showed a decrease in LVEF during stress, accompanied by a significant increase in entropy. The intra- and inter-observer reproducibility was excellent for both rest and stress studies. There was a moderate correlation (r = 0.5, p = 0.01) between GBPS and TTE, with a mean difference value of - 1.7 (95% confidence interval - 9.8; 6.4; p = 0.06) in ΔLVEF. CONCLUSION: Low-dose dobutamine stress GBPS performed with high-efficiency CZT-SPECT cameras can be performed for evaluating stress-induced changes in LV contractility and dyssynchrony with lower acquisition time. A dobutamine dose of 10 µg/kg/min can potentially suffice to detect stress-induced changes in patients with ICM during GBPS. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04508608 (August 7, 2020).

Health economics-based verification of functional myocardial ischemia evaluation of stable coronary artery disease in Japan: A long-term longitudinal study using propensity score matching.

BACKGROUND: The procedural numbers and medical costs of percutaneous coronary intervention (PCI), mainly elective PCI, have been increasing in Japan. Owing to increased interest in the appropriateness of coronary revascularization, we conducted this medical economics-based evaluation of testing and diagnosis of stable coronary artery disease (CAD). METHODS AND RESULTS: We reviewed patients' medical insurance data to identify stable CAD patients who underwent coronary computed tomography angiography, cardiac single-photon emission computed tomography, coronary angiography, or fractional flow reserve. Subjects were divided into anatomical and functional evaluation groups according to the modality of testing, and background factors were matched by propensity score. The endpoints were major adverse cardiovascular events (MACE), life years (LYs), medical costs, and cost-effectiveness analysis (CEA). The observations were performed for 36 months. MACE, medical costs, and CEA of the functional group in the overall category were trending to be better than the anatomical group (MACE, P = .051; medical costs: 3,105 US$ vs 4,430 US$, P = .007; CEA: 2,431 US$/LY vs 2,902 US$/LY, P = .043). CONCLUSIONS: The functional evaluation approach improved long-term clinical outcomes and reduced cumulative medical costs. As a result, the modality composition of functional myocardial ischemia evaluation was demonstrated to offer superior cost-effectiveness in stable CAD.

Comprehensive assessment of myocardial remodeling in ischemic heart disease by synchrotron propagation based X-ray phase contrast imaging.

Cardiovascular research is in an ongoing quest for a superior imaging method to integrate gross-anatomical information with microanatomy, combined with quantifiable parameters of cardiac structure. In recent years, synchrotron radiation-based X-ray Phase Contrast Imaging (X-PCI) has been extensively used to characterize soft tissue in detail. The objective was to use X-PCI to comprehensively quantify ischemic remodeling of different myocardial structures, from cell to organ level, in a rat model of myocardial infarction. Myocardial infarction-induced remodeling was recreated in a well-established rodent model. Ex vivo rodent hearts were imaged by propagation based X-PCI using two configurations resulting in 5.8 µm and 0.65 µm effective pixel size images. The acquired datasets were used for a comprehensive assessment of macrostructural changes including the whole heart and vascular tree morphology, and quantification of left ventricular myocardial thickness, mass, volume, and organization. On the meso-scale, tissue characteristics were explored and compared with histopathological methods, while microstructural changes were quantified by segmentation of cardiomyocytes and calculation of cross-sectional areas. Propagation based X-PCI provides detailed visualization and quantification of morphological changes on whole organ, tissue, vascular as well as individual cellular level of the ex vivo heart, with a single, non-destructive 3D imaging modality.

Functional Assessment of Myocardial Bridging With Conventional and Diastolic Fractional Flow Reserve: Vasodilator Versus Inotropic Provocation.

Background Functional assessment of myocardial bridging (MB) remains clinically challenging because of the dynamic nature of the extravascular coronary compression with a certain degree of intraluminal coronary reduction. The aim of our study was to assess performance and diagnostic value of diastolic-fractional flow reserve (d-FFR) during dobutamine provocation versus conventional-FFR during adenosine provocation with exercise-induced myocardial ischemia as reference. Methods and Results This prospective study includes 60 symptomatic patients (45 men, mean age 57±9 years) with MB on the left anterior descending artery and systolic compression ≥50% diameter stenosis. Patients were evaluated by exercise stress-echocardiography test, and both conventional-FFR and d-FFR in the distal segment of left anterior descending artery during intravenous infusion of adenosine (140 µg/kg per minute) and dobutamine (10-50 µg/kg per minute), separately. Exercise-stress-echocardiography test was positive for myocardial ischemia in 19/60 patients (32%). Conventional-FFR during adenosine and peak dobutamine had similar values (0.84±0.04 versus 0.84±0.06, P=0.852), but d-FFR during peak dobutamine was significantly lower than d-FFR during adenosine (0.76±0.08 versus 0.79±0.08, P=0.018). Diastolic-FFR during peak dobutamine was significantly lower in the exercise-stress-echocardiography test -positive group compared with the exercise- stress-echocardiography test -negative group (0.70±0.07 versus 0.79±0.06, P<0.001), but not during adenosine (0.79±0.07 versus 0.78±0.09, P=0.613). Among physiological indices, d-FFR during peak dobutamine was the only independent predictor of functionally significant MB (odds ratio, 0.870; 95% CI, 0.767-0.986, P=0.03). Receiver-operating characteristics curve analysis identifies the optimal d-FFR during peak dobutamine cut-off ≤0.76 (area under curve, 0.927; 95% CI, 0.833-1.000; P<0.001) with a sensitivity, specificity, and positive and negative predictive value of 95%, 95%, 90%, and 98%, respectively, for identifying MB associated with stress-induced ischemia. Conclusions Diastolic-FFR, but not conventional-FFR, during inotropic stimulation with high-dose dobutamine, in comparison to vasodilatation with adenosine, provides more reliable functional significance of MB in relation to stress-induced myocardial ischemia.

Role of quantitative myocardial blood flow and 13N-ammonia washout for viability assessment in ischemic cardiomyopathy.

OBJECTIVE: Positron emission tomography (PET) integrating assessment of perfusion with 13N-ammonia (NH3) and viability with 18F-fluorodeoxyglucose (FDG) has high accuracy to identify viable, hibernating myocardium. We tested whether quantification of myocardial blood flow (MBF) and washout (k2) can predict myocardial viability using FDG as standard of reference. METHODS: In 180 consecutive patients with ischemic cardiomyopathy, myocardium was categorized on a segment-level into normal, ischemic, hibernating, and scar. From dynamic images, stress MBF, rest MBF, and k2 were derived and myocardial flow reserve (MFR) and volume of distribution (VD) were calculated. RESULTS: Across myocardial tissues, all parameters differed significantly. The area under the curve (AUC) was 0.564 (95% CI 0.527-0.601), 0.635 (0.599-0.671), 0.553 (0.516-0.591), 0.520 (0.482-0.559), and 0.560 (0.522-0.597) for stress MBF, rest MBF, MFR, k2, and VD. The generalized linear mixed model correctly classified 81% of scar as viable, hibernating myocardium. If the threshold of rest MBF to predict viability was set to 0.45 mL·min-1·g-1, sensitivity and specificity were 96% and 12%, respectively. CONCLUSION: Quantitative NH3 PET parameters have low to moderate diagnostic performance to predict viability in ischemic cardiomyopathy. However, if rest MBF falls below 0.45 mL·min-1·g-1, viability testing by FDG-PET may be safely deferred.

Incremental value of myocardial wall motion and thickening to perfusion alone by gated SPECT myocardial perfusion imaging for viability assessment in patients with ischemic heart failure.

PURPOSE: The objective of this study was to assess the incremental value of myocardial wall motion and thickening compared with perfusion alone obtained from gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) in diagnosing myocardial viability in patients with ischemic heart failure. METHODS: Eighty-three consecutive patients with ischemic heart failure who underwent both 99mTc-MIBI gated SPECT MPI and 18F-FDG positron emission tomography (PET) myocardial metabolic imaging were retrospectively enrolled. SPECT/PET myocardial viability was defined as the reference standard. Segmental myocardial perfusion, wall motion, and thickening were measured by an automated algorithm from gated SPECT MPI. Univariate and stepwise multivariate analysis were conducted to establish an optimal multivariate model for predicting hibernating myocardium and scar. RESULTS: Among the 1411 segments evaluated, 774 segments had normal perfusion and 637 segments had decreased perfusion. The latter were classified by 18F-FDG PET into 338 hibernating segments and 299 scarred segments. The multivariate regression analysis showed that the model that combined myocardial perfusion uptake with wall motion and thickening scores had the optimal predictive efficiency to distinguish hibernating myocardium from scar in the segments with decreased perfusion. The model had the largest C-statistic (0.753 vs 0.666, P < 0.0001), and the global chi-square was increased from 53.281 to 111.234 when compared with perfusion alone (P < 0.001). CONCLUSIONS: Assessment of myocardial wall motion and thickening in addition to conventional perfusion uptake in the segments with decreased perfusion enables better differentiation of hibernating myocardium from scar in patients with ischemic heart failure. Considering wide availability and high cost-effectiveness, regional myocardial function integrated with perfusion on gated SPECT MPI has great promise to become a clinical tool in the assessment of myocardial viability.