Impact of Coronary Plaque on the Precision of Computational Fractional Flow Reserve Derived from CTA / 中山大学学报(医学科学版)

ObjectiveThe fractional flow reserve （FFR） computed from coronary computed tomographic （CT） angiograms makes it possible to noninvasively assess coronary artery disease， but the impact of plaque on FFR derived from computed tomography angiography （CTA） is still unknown. The study used invasive FFR as the reference standard to analyze the impact of plaque on coronary computed tomography angiography （CCTA）-based quantitative flow ratio （CT-QFR）. MethodsThe retrospective study included 108 patients with suspected coronary heart disease （CHD） who underwent both CCTA and FFR within 60 days. CCTA images were analyzed by the software. We obtained the CT-QFR of target vessels， perfomed the quantitative and qualitative analyses on target vascular plaques， including total plaque volume （TPV）， plaque burden， calcified plaque volume （CPV）， fibrous plaque volume （FPV）， lipid plaque volume （LPV）， and the presence or absence of high-risk plaque. ResultsAccording to the difference between CT-QFR and FFR at blood vessel level， 137 target vessels of 108 patients were divided into the overestimated group （difference＞0.03， n＝29）， reference group （-0.03≤difference≤0.03， n＝88） and underestimated group （difference＜-0.03， n＝20）. The underestimated group （14.81mm3） presented higher LPV than overestimated group （1.97mm3， P < 0.05）. There was a negative correlation between LPV and the difference （P＜0.05）. ConclusionsWhen CT-QFR is used to estimate hemodynamics of coronary artery stenosis， the presence of lipid plaque may underestimate the virtual FFR.

Research progress on image-based calculation of coronary artery fractional flow reserve / 生物医学工程学杂志

Coronary artery fractional flow reserve (FFR) is a critical physiological indicator for assessment of impaired blood flow caused by coronary artery stenosis. The wire-based invasive measurement of blood flow pressure gradient across stenosis is the gold standard for clinical measurement of FFR. However, it has the risk of vascular injury and requires the use of vasodilators, increasing the time and overall cost of interventional examination. Coronary imaging is playing an important role in clinical diagnosis of stenotic lesions, evaluation of severity of lesions, and planning of therapies. In recent years, the computation of FFR based on the physiological information of blood flow obtained from routinely collected coronary image data has become a research focus in this field. This technique reduces the cost of physiological assessment of coronary lesions and the use of pressure wires. It is beneficial to strengthen the physiological guidance in interventional therapy. In order to better understand this emerging technique, this paper highlights its implementation principle and diagnostic performance, analyzes practical problems and current challenges in clinical applications, and discusses possible future development.

Índices fisiológicos não hiperêmicos ­ base teórica, aplicações clínicas e limitações / Non-hyperemic pressure ratios ­ theoretical basis, clinical applications, and limitations

A fisiologia coronariana tornou-se o padrão de tratamento para avaliar o significado funcional da doença aterosclerótica coronariana. Ela permite identificar isquemia miocárdica em nível de vaso, discriminar os padrões funcionais da doença aterosclerótica e orientar a necessidade de revascularização; complementar o planejamento da intervenção coronária percutânea e confirmar o sucesso funcional dessa última. Em uma edição anterior do Journal of Transcatheter Interventions, apresentamos uma revisão abrangente sobre o fluxo fracionado de reserva do miocárdio. Apesar do robusto corpo de evidências que apoiam seu uso, a aceitação clínica do fluxo fracionado de reserva é variável e excessivamente baixa em muitas áreas do mundo. O aumento percebido no tempo do procedimento, o uso de agentes hiperêmicos com seus correspondentes custos e desconforto do paciente, e a dificuldade de interpretação dos resultados em determinadas situações anatômicas contribuíram para a adoção limitada do método. A introdução do índice de fluxo instantâneo no período livre de ondas superou a maioria dessas limitações. Apoiada por uma validação técnica sólida e dados de desfechos clínicos, o índice de fluxo instantâneo no período livre de ondas recebeu as mesmas indicações clínicas que o fluxo fracionado de reserva nas recomendações mais recentes das diretrizes. Isso foi seguido pela introdução de outros índices pressóricos não hiperêmicos, já comercialmente disponíveis. Neste artigo, revisamos as bases fisiológicas que justificam o uso de índices pressóricos não hiperêmicos, sua validação técnica e clínica e dados de desfechos clínicos, além de discutirmos suas aplicações em situações anatômicas específicas, com exemplos de casos dos autores, sempre que aplicável.

Coronary physiology has become the standard of care to assess the functional significance of coronary atherosclerotic disease. It allows for identification of myocardial ischemia on a vessel level, discrimination of the functional patterns of atherosclerotic disease, guidance for the need of revascularization, complements the planning of percutaneous coronary intervention and verification of the functional success of percutaneous coronary intervention. On a previous issue of the Journal of Transcatheter Interventions, we presented a comprehensive review about fractional flow reserve. Despite the robust body of evidence supporting its use, the clinical use of fractional flow reserve is variable, and unreasonably low in many areas around the globe. The perceived increase in procedure time, the use of hyperemic agents with its related costs and patient discomfort, and difficulty in interpreting results in certain anatomical scenarios have contributed to the limited adoption of fractional flow reserve. The introduction of instantaneous wave-free ratio overcame most of these limitations. Supported by sound technical validation, and clinical outcomes data, instantaneous wave-free ratio received the same clinical indications as fractional flow reserve in the most recent guidelines recommendations. This was followed by the introduction of other non- hyperemic pressure ratios for commercial use. In the current manuscript we review the physiological basis that supports the use of non-hyperemic pressure ratios, their technical and clinical validation, clinical outcomes data, and discuss its applications on specific anatomic scenarios, with examples of cases from the authors, whenever applicable.

Avaliação Prognóstica da Reserva de Fluxo Fracionada em Diferentes Estratos nos Pacientes com Doença Arterial Coronariana / Prognostic Assessment of Fractional Flow Reserve in Different Strata in Patients with Coronary Artery Disease

Resumo Fundamento Existem dados limitados sobre a evolução clínica de lesões coronarianas não tratadas de acordo com sua gravidade funcional no mundo real. Objetivo Este estudo teve como objetivo avaliar os resultados clínicos de até 5 anos em pacientes com lesões revascularizadas com reserva de fluxo fracionada (FFR) ≤ 0,8 e em pacientes com lesões não revascularizadas com FFR > 0,8. Métodos A avaliação pelo FFR foi realizada em 218 pacientes seguidos por até 5 anos. Os participantes foram classificados com base na FFR no grupo isquêmico (≤ 0,8, grupo intervenção, n = 55), no grupo FFR normal-baixa (> 0,8-0,9, n = 91) e no grupo FFR normal-alta (> 0,9, n = 72). O desfecho primário foram eventos cardíacos adversos maiores (ECAMs), um composto de morte, infarto do miocárdio e necessidade de nova revascularização. O nível de significância adotado neste estudo foi alfa = 0,05; deste modo, resultados com valores de p < 0,05 foram considerados estatisticamente significativos. Resultados A maioria dos participantes era do sexo masculino (62,8%) com média de idade de 64,1 anos. Diabetes estava presente em 27%. À angiografia coronariana, a gravidade da estenose avaliada foi de 62%, 56,4% e 54,3% nos grupos isquêmico, FFR normal-baixa e FFR normal-alta, respectivamente (p < 0,05). O período médio de acompanhamento foi de 3,5 anos. A incidência ECAM foi de 25,5%, 13,2% e 11,1%, respectivamente (p = 0,037). Não houve diferença na incidência de ECAM entre os grupos FFR normal-baixa e FFR normal-alta (p = NS). Conclusão Pacientes com FFR indicativa de isquemia apresentaram piores desfechos quando comparados aos dos grupos não isquêmicos. Entre os grupos que apresentaram valores de FFR considerados normal-baixo e normal-alto, não houve diferença na incidência de eventos. Há necessidade de estudos de longo prazo e com grande número de pacientes para melhor avaliar os desfechos cardiovasculares em pacientes portadores de estenose coronariana moderada com valores de FFR entre 0,8 e 1,0.

Abstract Background There are limited real-world data on the clinical course of untreated coronary lesions according to their functional severity. Objective To evaluate the 5-year clinical outcomes of patients with revascularized lesions with fractional flow reserve (FFR) ≤ 0.8 and patients with non-revascularized lesions with FFR > 0.8. Methods The FFR assessment was performed in 218 patients followed for up to 5 years. Participants were classified based on FFR into ischemia group (≤ 0.8, intervention group, n = 55), low-normal FFR group (> 0.8-0.9, n = 91), and high-normal FFR group (> 0.9, n = 72). The primary endpoint was major adverse cardiac events (MACEs), a composite of death, myocardial infarction, and need for repeat revascularization. The significance level was set at 0.05; therefore, results with a p-value < 0.05 were considered statistically significant. Results Most patients were male (62.8%) with a mean age of 64.1 years. Diabetes was present in 27%. On coronary angiography, the severity of stenosis was 62% in the ischemia group, 56.4% in the low-normal FFR group, and 54.3% in the high-normal FFR group (p<0.05). Mean follow-up was 3.5 years. The incidence of MACEs was 25.5%, 13.2%, and 11.1%, respectively (p=0.037). MACE incidence did not differ significantly between the low-normal and high-normal FFR groups. Conclusion Patients with FFR indicative of ischemia had poorer outcomes than those in non-ischemia groups. There was no difference in the incidence of events between the low-normal and high-normal FFR groups. Long-term studies with a large sample size are needed to better assess cardiovascular outcomes in patients with moderate coronary stenosis with FFR values between 0.8 and 1.0.

Prognostic value of age, creatinine, and left ventricular ejection fraction risk score in patients evaluated with fractional flow reserve: a cross-sectional study

SUMMARY OBJECTIVE: In this study, we investigated the relationship between age, creatinine, and left ventricular ejection fraction risk score and the severity of coronary lesions detected by applying fractional flow reserve in the patient group presenting with chronic coronary syndrome. Also, we presented long-term follow-up results in patients whose age, creatinine, and left ventricular ejection fraction score was evaluated by the fractional flow reserve procedure. METHODS: This study was planned retrospectively and in two centers. For this purpose, 114 patients who met the study criteria and who underwent elective fractional flow reserve between January 2014 and January 2019 were included in the study. Age, creatinine, and left ventricular ejection fraction was calculated as age/left ventricular ejection fraction +1 (if estimated glomerular filtration rate<30 mL/min). RESULTS: They were divided into two groups according to the cutoff value of the age, creatinine, and left ventricular ejection fraction score. A total of 76 patients had an age, creatinine, and left ventricular ejection fraction score of ≤1.17 (Group I) and 38 patients had an age, creatinine, and left ventricular ejection fraction score of >1.17 (Group II). The number of patients with severe lesions in fractional flow reserve was significantly higher in Group II compared with Group I (60.5 vs. 32.9%, p=0.005). According to the Kaplan-Meier analysis, a significant increase was observed in major adverse cardiac events and mortality during the follow-up period in the group with a high-risk score (Log Rank: 15.01, p<0.001 and Log Rank: 8.51, p=0.004, respectively). CONCLUSION: In light of the data we obtained from our study, we found a correlation between the severity of the lesion detected in fractional flow reserve and the age, creatinine, and left ventricular ejection fraction scores. In addition, we found that patients with high age, creatinine, and left ventricular ejection fraction scores had higher mortality and major adverse cardiac events rates during follow-up.

Quantitative assessment of right ventricular myocardial blood flow with SPECT in pulmonary hypertension animal models / 中华核医学与分子影像杂志

Objective:To explore the changes of right ventricular myocardial perfusion in pulmonary arterial hypertension (PAH) pig models with a quantitative analysis technique based on dynamic SPECT myocardial perfusion imaging, and analyze the relationship between myocardial blood flow, hemodynamics and right ventricular function.Methods:Eleven Chinese miniature pigs (all males, 6-8 months old) weighing 25-30 kg were selected. The PAH models were established by ligating the main pulmonary artery and embolizing the right lower pulmonary artery. After the models were established, dynamic myocardial perfusion imaging with one-day resting/adenosine stress 99Tc m-methoxyisobutylisonitrile (MIBI) SPECT was performed, and the quantitative parameters of left and right ventricles were obtained, including stress myocardial blood flow (SMBF), rest myocardial blood flow (RMBF) and myocardial flow reserve (MFR: the ratio of stress to rest myocardial blood flow). Right heart catheterization was performed to evaluate the mean pulmonary arterial pressure (mPAP), and the right heart function index tricuspid annular plane systolic excursion (TAPSE) was measured by transthoracic echocardiography. According to TAPSE, animals were divided into right heart function preserved group ( n=5, TAPSE≥17 mm) and right heart dysfunction group ( n=4, TAPSE<17 mm). Pearson correlation analysis and the independent-sample t test were used for data analysis. Results:Nine experimental pig models were established with increased mPAP of (38.1 ± 11.6 ) mmHg (1 mmHg=0.133 kPa). Myocardial perfusion imaging showed clear radiotracer uptake in the right heart and myocardial hypertrophy. There was a significant positive correlation between right ventricular myocardial RMBF ((0.71±0.13) ml·min -1·g -1) and mPAP ( r=0.94, P< 0.001). The SMBF in the decreased right ventricular function group was significantly lower than that in the preserved right ventricular function group ((1.66±0.35) vs (2.24±0.30) ml·min -1·g -1;t=2.68, P=0.032). Conclusion:SPECT myocardial blood flow quantification can be used to evaluate the right ventricular myocardial blood flow in pig models of PAH.

Value of SPECT myocardial perfusion imaging and coronary flow reserve combined with coronary artery calcium score in the diagnosis of obstructive coronary artery disease / 中华核医学与分子影像杂志

Objective:To study the value of myocardial perfusion imaging (MPI) and coronary flow reserve (CFR) combined with coronary artery calcium score (CACS) in the diagnosis of obstructive coronary artery disease (CAD).Methods:From January 2019 to December 2020, 96 confirmed or suspective CAD patients (65 males, 31 females; age: 30-81 years) who completed rest/stress MPI, CFR and CACS defection in Fuwai Central China Cardiovascular Hospital were retrospectively analyzed. Coronary angiography (CAG) was used as the diagnostic standard to calculate the sensitivity and accuracy of MPI, CFR and MPI/CFR combined with CACS in the diagnosis of CAD. The χ2 test was used to compare the diagnostic efficiency of different methods. Results:The diagnostic sensitivity of MPI was 76.06%(54/71), and the accuracy was 75.00%(72/96), while the sensitivity increased to 97.18%(69/71; χ2=13.67, P<0.001) and the accuracy increased to 87.50%(84/96; χ2=4.92, P=0.020) with significant differences after combined with CACS. The sensitivity and accuracy of CFR were 91.55%(65/71)and 87.50%(84/96), which increased to 97.18%(69/71; χ2=2.12, P=0.137) and 89.58%(86/96; χ2=0.21, P=0.411) with no significant differences after combined with CACS. The sensitivity of MPI in the diagnosis of three-vessel CAD was 70.00%(21/30), which increased to 100%(30/30; χ2=7.75, P=0.004) after combined with CACS; while the sensitivity of MPI combined with CACS in the diagnosis of single-vessel and double-vessel CAD were not significantly improved ( χ2 values: 3.29, 1.51, P values: 0.114, 0.416). Conclusion:The combination of MPI and CACS can significantly improve the diagnostic efficiency of CAD, contributed by the improvement of the diagnostic sensitivity in three-vessel disease; whereas the diagnostic efficiency of CFR for CAD is not significantly improved after combined with CACS.

Relationship between coronary flow reserve by CZT SPECT and invasive coronary fractional flow reserve and its potential clinical value / 中华核医学与分子影像杂志

Objective:To evaluate the relationship between regional coronary flow reserve (CFR) obtained from cadmium-zinc-telluride SPECT(CZT SPECT) myocardial functional perfusion imaging (MFPI) and invasive fractional flow reserve (FFR) measured during coronary angiography (CAG) and its clinical value in guiding coronary interventions.Methods:Forty-two patients (30 males, 12 females, age (63.3±9.8) years) who completed CZT SPECT MFPI in the First Affiliated Hospital of Nanjing Medical University from June 2022 to September 2022 and underwent CAG within 3 months were included retrospectively. The concordance of CFR and FFR for diagnosing myocardial ischemia (CFR<2.0 and FFR<0.8) was calculated at the vascular level. The diagnostic efficacy of coronary stenosis≥70% for decreased myocardial blood flow (CFR<2.0) was calculated. Kappa test was used to analyze the data. Results:A total of 126 major coronary arteries were identified in 42 patients, of which 30(23.8%) had a CFR<2.0 by CZT SPECT and 33(26.2%) had stenosis≥70% in CAG. A total of 32 coronary vessels were performed with MFPI CFR and FFR measurements, of which 6 were both decreased and 21 were both normal, so the concordance rate was 84.4%(27/32)( Kappa=0.612, P<0.001). Among 33 coronary vessels with stenosis≥70%, 13 were with CFR≥2.0. Among 30 coronary vessels with CFR<2.0, 10 were with stenosis<70%. When using stenosis≥70% to diagnose CFR decreasing, the sensitivity was 66.7%(20/30), specificity was 86.5%(83/96), positive predictive value was 60.6%(20/33), negative predictive value was 89.2%(83/93), and accuracy was 81.7%(103/126). Conclusions:The concordance between CFR and FFR for the diagnosis of myocardial ischemia is good. Nearly 1/3 of the coronary arteries with decreased CFR have stenosis<70%, whereas nearly 40% of the coronary arteries with stenosis≥70% are not result in myocardial ischemia. Regional CFR determined by CZT SPECT may have potentially significant clinical value in the diagnosis of coronary artery disease and decision-making of coronary intervention.

The impact of image quality on the diagnostic performance of CT-derived fractional flow reserve / 中华放射学杂志

Objective:To explore the impact of coronary CT angiography (CCTA) image quality and related factors on the diagnostic performance of CT-derived fractional flow reserve (CT-FFR).Methods:Based on the CT-FFR CHINA trial, the prospective multicenter trial enrolled patients with suspected coronary artery disease who underwent CCTA, CT-FFR and FFR measurement. The subjective and objective assessments of CCTA image were performed on a per-vessel level. The objective assessments included the enhancement degree of coronary artery, the signal-to-noise ratio (SNR) of the aortic root. We used χ 2 test and DeLong test to compare the diagnostic performance of CT-FFR with FFR as the reference standard in different subjective groups (non-artifact vs. artifact), enhancement degree of coronary artery groups (≤400 vs. 401-500 vs.>500 HU), SNR of the aortic root groups (≤16.9 vs.>16.9), body mass index (BMI) groups (<25 kg/m 2 vs.≥25 kg/m 2) and heart rate groups (<75 bpm vs.≥75 bpm). FFR and CT-FFR values≤0.80 was identified as myocardial ischemia. Results:The study enrolled 317 patients with 366 vessels. All target vessels in CCTA images were successfully analyzed by CT-FFR. The accuracy, sensitivity, specificity, positive predictive value, negative predictive value and AUC of the non-artifact group were 90.45%, 86.75%, 93.10%, 90.00%, 90.76% and 0.928, respectively, and those of the artifact group were 83.23%, 87.21%, 79.01%, 81.52%, 85.33% and 0.869, respectively. The differences in accuracy and specificity were statistically significant (χ 2=4.23, P=0.040; χ 2=8.55, P=0.003). The diagnostic efficacy of CT-FFR had no statistically significant differences among different objective groups (all P>0.05). Conclusions:The artifact of CCTA image has an effect on CT-FFR in the diagnosis of myocardial ischemia. The degree of vascular enhancement, SNR, BMI, and heart rate have no significant effect on the diagnostic performance of CT-FFR.

Ajustando a RFR por Preditores de Discordância, "A RFR Ajustada": Uma Metodologia Alternativa para Melhorar a Capacidade Diagnóstica dos Índices Coronarianos / Adjusting RFR by Predictors of Disagreement, "The Adjusted RFR": An Alternative Methodology to Improve the Diagnostic Capacity of Coronary Indices

Resumo Fundamento Os limiares de corte para a "relação do ciclo completo de repouso" (RFR) oscilam em diferentes séries, sugerindo que as características da população podem influenciá-los. Da mesma forma, foram documentados preditores de discordância entre a RFR e a reserva de fluxo fracionado (FFR). O Estudo RECOPA, mostrou que a capacidade diagnóstica está reduzida na "zona cinzenta" da RFR, tornando necessária a realização de FFR para descartar ou confirmar isquemia. Objetivos Determinar os preditores de discordância, integrar as informações que eles fornecem em um índice clínico-fisiológico: a "RFR Ajustada", e comparar sua concordância com o FFR. Métodos Usando dados do Estudo RECOPA, os preditores de discordância em relação à FFR foram determinados na "zona cinzenta" da RFR (0,86 a 0,92) para construir um índice ("RFR Ajustada") que pesaria a RFR juntamente com os preditores de discordância e avaliar sua concordância com a FFR. Resultados Foram avaliadas 156 lesões em 141 pacientes. Os preditores de discordância foram: doença renal crônica, cardiopatia isquêmica prévia, lesões não envolvendo a artéria descendente anterior esquerda e síndrome coronariana aguda. Embora limitada, a "RFR Ajustada" melhorou a capacidade diagnóstica em comparação com a RFR na "zona cinzenta" (AUC-RFR = 0,651 versus AUC-"RFR Ajustada" = 0,749), mostrando também uma melhora em todos os índices diagnósticos quando foram estabelecidos limiares de corte otimizados (sensibilidade: 59% a 68%; especificidade: 62% a 75%; acurácia diagnóstica: 60% a 71%; razão de verossimilhança positiva: 1,51 a 2,34; razão de verossimilhança negativa: 0,64 a 0,37). Conclusões Ajustar a RFR integrando as informações fornecidas pelos preditores de discordância para obter a "RFR Ajustada" melhorou a capacidade diagnóstica em nossa população. Mais estudos são necessários para avaliar se os índices clínico-fisiológicos melhoram a capacidade diagnóstica da RFR ou de outros índices coronarianos.

Abstract Background Cutoff thresholds for the "resting full-cycle ratio" (RFR) oscillate in different series, suggesting that population characteristics may influence them. Likewise, predictors of discordance between the RFR and fractional flow reserve (FFR) have been documented. The RECOPA Study showed that diagnostic capacity is reduced in the RFR "grey zone", requiring the performance of FFR to rule out or confirm ischemia. Objectives To determine predictors of discordance, integrate the information they provide in a clinical-physiological index, the "Adjusted RFR", and compare its agreement with the FFR. Methods Using data from the RECOPA Study, predictors of discordance with respect to FFR were determined in the RFR "grey zone" (0.86 to 0.92) to construct an index ("Adjusted RFR") that would weigh RFR together with predictors of discordance and evaluate its agreement with FFR. Results A total of 156 lesions were evaluated in 141 patients. Predictors of discordance were: chronic kidney disease, previous ischemic heart disease, lesions not involving the anterior descending artery, and acute coronary syndrome. Though limited, the "Adjusted RFR" improved the diagnostic capacity compared to the RFR in the "grey zone" (AUC-RFR = 0.651 versus AUC-"Adjusted RFR" = 0.749), also showing an improvement in all diagnostic indices when optimal cutoff thresholds were established (sensitivity: 59% to 68%; specificity: 62% to 75%; diagnostic accuracy: 60% to 71%; positive likelihood ratio: 1.51 to 2.34; negative likelihood ratio: 0.64 to 0.37). Conclusions Adjusting the RFR by integrating the information provided by predictors of discordance to obtain the "Adjusted RFR" improved the diagnostic capacity in our population. Further studies are required to evaluate whether clinical-physiological indices improve the diagnostic capacity of RFR or other coronary indices.

Fractional flow reserve [FFR] guided stenting of left main coronary artery in acute coronary syndrome: A single centre experience

The present study assesses the clinical outcomes after left main coronary stenting, using clinical evaluation, angiography, and Fractional Flow Reserve (FFR). A prospective observational study was conducted on 72 patients undergoing left main coronary artery (LMCA) stenting, transthoracic echocardiography, coronary angiography, and percutaneous coronary intervention were done and FFR was recorded. At the end of 6 months, follow up check angiography, FFR study were performed. The stent was placed from LMCA to left anterior descending artery (LAD) artery among 45.83% of patients and 9.72% had from LMCA to Left circumflex artery. The mortality rate was 8.33%. The fractional flow reserve was 0.81 on an average ranging from 0.58 to 0.90. Relatively low incidence of major cardiac event was noted among patients with single vessel disease and ostial LMCA disease.

Fluxo fracionado de reserva do miocárdio: bases fisiológicas, aplicações clínicas e limitações / Fractional flow reserve: physiological bases, clinical applications and limitations

A avaliação fisiológica invasiva da circulação coronariana emergiu nos últimos anos como uma abordagem diagnóstica valiosa no manejo de pacientes com síndrome coronariana crônica, contornando limitações importantes como avaliar função a partir da anatomia e a baixa resolução espacial associada à angiografia ou testes não invasivos. O valor das medidas de fluxo hiperêmico para estimar a relevância funcional das estenoses coronárias é suportado por um grande número de estudos. O objetivo do presente artigo é rever as principais bases fisiológicas, aplicações clínicas e limitações do fluxo fracionado de reserva do miocárdio, o principal índice utilizado na avaliação funcional invasiva da circulação coronariana.

Invasive physiological assessment of the coronary circulation has emerged in recent years as a valuable diagnostic approach in the management of patients with chronic coronary syndrome, overcoming important limitations such as evaluating function from the anatomy and the low spatial resolution associated with angiography or non-invasive tests. The value of hyperemic flow measurements to estimate the functional relevance of coronary stenoses is supported by many studies. The aim of this paper is to review the physiological bases, clinical applications and limitations of myocardial fractional flow reserve, the main index used in the invasive functional assessment of the coronary circulation.

Research Progress of Coronary Physiological Evaluation Development in 2021 / 医用生物力学

Cardiovascular disease is one of the most serious diseases endangering human life and health. In China, 2 out of every 5 people die of cardiovascular diseases. Myocardial ischemia is one of the important cardiovascular diseases. Fractional flow reserve (FFR) is used to quantify myocardial ischemia in epicardial stenoses. Index of microvascular resistance (IMR) is an invasive index for quantitative evaluation of coronary microcirculation. Traditional FFR and IMR measurements rely on guide wires to perform interventional measurements under the maximum hyperemia state,so as to assist the diagnosis of myocardial ischemia clinically. Coronary angiography-derived FFR and IMR without using invasive pressure-wire measurement, hyperemic stimulus and contraindications can assist the diagnosis and treatment of percutaneous coronary intervention by fast simultaneous calculation of FFR and IMR. In this review, the research progress of coronary angiography-derived FFR and IMR as well as other coronary physiological evaluation in recent years were summarized. It is of great clinical value to further study the combination of coronary angiography-derived FFR and IMR in functional research of coronary circulation from macro to micro.

Valoración de la reserva contráctil y cronotrópica en estudios de eco estrés negativos para isquemia miocárdica / Contractile and chronotropic reserve assessment in stress echocardiography studies negative for myocardial ischemia

RESUMEN Introducción: Si bien el principal objetivo del ecocardiograma estrés (EE) es analizar los cambios en la motilidad parietal, el análisis de otras variables como la reserva contráctil (RCon) por el método de elastancia y la reserva cronotrópica (RCro) permiten agregar valor pronóstico al estudio. No obstante, las mismas no suelen analizarse ni informarse en la mayoría de los estudios de EE en nuestro medio. Objetivos: Comparar las características clínicas y ecocardiográficas de pacientes a quienes se les realizó un EE con ejercicio negativo para isquemia miocárdica de acuerdo con la presencia o no de RCon y RCro. Material y métodos: Estudio retrospectivo realizado sobre 73 pacientes con EE con ejercicio, sin isquemia. De acuerdo con la presencia o ausencia de RCon y RCro se los dividió en tres grupos. Grupo 1: presencia de ambas reservas; grupo 2: presencia de solo una reserva y grupo 3: ausencia de ambas reservas. La RCon se determinó mediante el cociente entre la tensión arterial sistólica y el volumen de fin de sístole tanto en reposo como en estrés (Valor normal: > 2) y la RCro se definió como el aumento mayor al 80% de la frecuencia cardíaca basal. Resultados: Se incluyeron 73 pacientes (64% varones, edad 63 ± 12 años). En el Grupo 1 se incluyeron 23 pacientes (62% varones, 59,8 ± 12,5 años), en el grupo 2, 29 pacientes (65% varones, 60,7 ± 13 años) y en el grupo 3, 21 pacientes (65% varones, 68,8 ± 7,8 años). Los pacientes sin ninguna reserva fueron más añosos y presentaron una tendencia a mayor prevalencia de los factores de riesgo tradicionales, más antecedentes de IAM y mayor uso de betabloqueantes. Desde el punto de vista ecocardiográfico, este mismo grupo presentó menores valores de fracción de eyección ventricular izquierda (FEVI) y strain longitudinal global (SLG) tanto en reposo como en esfuerzo, mayor masa ventricular, y en la ergometría menor cantidad de minutos de ejercicio realizado. Se realizó una regresión logística binaria con aquellas variables asociadas a la ausencia de RCon y RCro. La edad (OR 1,12, IC95% 1,02-1,22; p = 0,01) y el valor de SLG en reposo (OR 0,68, IC95% 0,51-0,90; p= 0,008) fueron las variables asociadas en forma independiente a la ausencia de ambas reservas. En una curva ROC, un valor de SLG de -18% fue el mejor punto de corte (área bajo la curva 0,72; IC 95% 0,57-0,87). Conclusiones: Los pacientes con EE negativo para isquemia miocárdica, y que además presentan ausencia de RCon y RCro tienen un perfil de riesgo más elevado. Esto podría estar asociado a mayor riesgo de eventos cardiovasculares durante el seguimiento.

ABSTRACT Background: While the primary objective of the stress echocardiography (stress echo) is to assess wall motion abnormalities, evaluation of other variables, such as contractile reserve (CR) via elastance, and chronotropic reserve (ChR), may add prognostic value to the study. However, these are unusually evaluated or reported in most stress echo studies in our field. Objectives: To compare clinical and echocardiographic characteristics in patients undergoing an exercise stress echo with negative results for myocardial ischemia based on the presence or absence of CR and ChR. Methods: A rRetrospective study in 73 patients, with exercise stress echo and no ischemia. Patients were divided into three groups, based on the presence or absence of CR and ChR. Group 1: presence of both; Group 2: presence of either of the two, and Group 3: absence of both. The CR was established using as the systolic blood pressure and end-systolic volume ratio, both at rest and under stress (normal value: >2), and the ChR was defined as a more than 80% increase in baseline heart rate. Results: The study enrolled 73 patients (64% males, aged 63±12 years). Group 1 included 23 patients (62% males, agedaged 59.8±12.5 years); Group 2 included 29 patients (65% males, aged 60.7±13 years), and Group 3 included 21 patients (65% males, aged 68.8±7.8 years). Patients with no reserve were older and showed a tendency to higher prevalence of traditional risk factors, a longer history of AMI and increased use of beta blockers. In the Echocardiographicallyechocardiographic study, his group had lower values of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) both at rest and under stress, a larger ventricular mass, and less minutes of exercise according toin the exercise stress test. A binary logistic regression was performed using variables associated with the absence of CR and ChR. Age (OR 1.12, 95% CI 1.02-1.22; p=0.01) and GLS at rest (OR 0.68, 95% CI 0.51-0.90; p=0.008) were variables independently associated with the absence of both reserves. On a ROC curve, a GLS of -18% was the best cutoff point (area under the curve 0.72). Conclusion: Patients with a stress echo negative for myocardial ischemia and absence of CR and ChR have a higher risk profile. This could be associated with a higher risk of cardiovascular events during the follow-up.

Potential role of fractional flow reserve-guided coronary artery bypass graft surgery / 中华胸心血管外科杂志

Objective:To investigate the potential guiding role of fractional flow reserve(FFR) in surgical revascularization by comparing the relationship between coronary fractional flow reserve(FFR) and blood flow pattern status of bypass graft.Methods:A total of 86 patients with coronary artery disease between March 2016 to October 2019 were included in the study, with 59 males and 27 females; the age ranged from 42 to 77 years old, with an average of(58±12) years old. According to the measured FFR value of the left anterior descending artery, they were divided into severe ischemic group(FFR<0.75), boundary group(0.75≤FFR<0.80) and mild ischemic group(FFR≥0.80). Transit time flow meter(TTFM) was used to evaluate the blood flow status of the bridge vessel from the left internal thoracic artery to the left anterior descending coronary artery.Results:Mean graft flow(MGF) was measured at(21.24±5.71)ml/min, (18.25±7.72)ml/min, (16.47±7.83)ml/min in severe ischemic group, boundary group and mild ischemic group. The results of mean pulsatility index(PI) was 2.58±0.96, 3.14±1.19 and 3.53±1.34, the ratio of diastolic flow during the entire graft flow was 0.63±0.10, 0.55±0.11 and 0.53±0.11, patients appeared systolic reverse flow was 2 cases(3.6%), 3 cases(18.8%) and 3 cases (20.0%), respectively. There were statistically significant differences in MGF( P=0.027)、PI( P=0.007)、the ratio of DF( P=0.001) and the quantity of patients appeared systolic reverse flow( P=0.027) between the three groups. Conclusion:Due to increasing severity of coronary artery stenosis, MGF and the ratio of diastolic flow increased, and there appears to be an decreased PI and quantity of patients appeared systolic reverse flow. The chance of bypass graft occlusion may increase for the near and middle term in mild to moderate functional coronary artery stenosis(FFR≥0.75). For patients with severe functional coronary artery stenosis(FFR<0.75), it can obtain satisfactory flow parameters and ideal clinical outcomes.

Study of quantitative flow ratio-guided surgical coronary artery revascularization strategy / 中华胸心血管外科杂志

Objective:To explore the feasibility of applying quantitative flow ratio(QFR) to assess the degree of coronary artery functional stenosis before surgery, and to guide coronary artery bypass grafting(CABG) revascularization strategy.Methods:The study prospectively included a total of 154 patients who were electively treated with CABG in the 11th ward of the Department of Cardiac Surgery of Beijing Anzhen Hospital from January 2019 to September 2020, and their coronary angiography visually showed stenosis of the coronary artery to perform QFR analysis to know the diseased blood vessels. For functional stenosis, the surgeon was blinded to the results of QFR analysis before surgery. Collect its baseline data, perioperative data and recent clinical outcomes for summary analysis.Results:One year later, the coronary artery CTA showed that the occlusion rate of functionally significant disease(QFR<0.8) was 5.5%, and that of non-functionally significant disease(QFR≥0.8) was 15.6%. There was no difference in angina class or repeat interventions between patients with or without occluded bypass grafts.Conclusion:According to QFR analysis, coronary arteries with functional non-significant disease have a higher risk of grafts failure than those with functionally significant disease. For coronary arteries with negative QFR lesions, the risk of occlusion of arterial grafts is higher than that of venous. However, this finding is not significantly related to clinical prognosis, because patients with patency or occlusion of the grafts in non-significant lesions have not found excessive angina pectoris or repeated coronary interventions. QFR-guided selection of coronary surgery strategies is safe and feasible.

Evaluación no invasiva de la significancia funcional de las lesiones coronarias mediante quantitative flow ratio (QFR): validación con reserva de flujo fraccional (FFR) / Functional significance of coronary artery lesions evaluated by quantitative flow ratio (QFR): a comparison fractional flow reserve (FFR)

RESUMEN: Introducción: La evaluación de lesiones coronarias mediante Reserva de Flujo Fraccional (FFR), es de elección para determinar su significancia funcional en el laboratorio de hemodinamia. La razón de flujo cuantitativo (Quantitative Flow Ratio, QFR) es una nueva técnica no invasiva para la evaluación de la significancia funcional de una estenosis coronaria, basada en el análisis de flujo a partir de la coronariografía diagnóstica, sin necesidad de hiperemia ni de la introducción de insumos adicionales. Objetivo: evaluar la correlación y valor predictivo del QFR comparado con FFR. Métodos: se seleccionaron arterias que contaban con medición de FFR realizados en nuestro centro y se analizó retrospectivamente el QFR a partir de las coronariografías de dichos estudios. Se excluyó lesiones de tronco y lesiones ostiales. La medición de FFR fue realizada con guía de presión ubicada distal al segmento afectado, mediante hiperemia con adenosina intracoronaria o intravenosa en infusión. Para el análisis de QFR se utilizan 2 proyecciones angiográficas ortogonales del vaso a interrogar con una separación de más de 25º entre ellas; ambas proyecciones deben coincidir en el eje para un correcto análisis. El análisis fue realizado por dos operadores, ciegos al resultado del FFR, utilizando el software QAngioXA (Medis ®, Netherland). Resultados: se analizaron 35 arterias, 57,1% Descendente Anterior (ADA), 20% Circunfleja (ACF) y 20% Derecha (ACD). El FFR promedio fue de 0,83±0,092 y 34,2% tuvieron como resultado un FFR ±0,80. El análisis retrospectivo del QFR se pudo realizar en 27 arterias; en las 8 restantes (22,9%) no fue posible su realización, ya sea por imágenes insuficientes o falta de perpendicularidad del segmento. El QFR promedio fue de 0,81±0,118. Hubo una buena correlación entre QFR y FFR (r =0,758; p0,8 pero QFR±0,8 en 3,7%; y FFR ±0,8 y QFR >0,8 en 3,7%. Así, el QFR tuvo una Sensibilidad: 90,9%, Especificidad: 93,8%; Valor Predictivo Positivo: 90,9%; Valor Predictivo Negativo: 93,8%; Likelihood Ratio Positivo: 14,55 y Likelihood Ratio Negativo: 0,1. La curva ROC mostró un área bajo curva: 0,923; 95% IC: 0,801-1,00. Conclusión: Los resultados del QFR en nuestra serie son similares a las mediciones de FFR. El uso de QFR podría ser una alternativa, rápida, económica y segura, en la evaluación fisiológica de lesiones coronarias. Se requieren mayores estudios clínicos para comprobar estos resultados.

ABSTRACT: Background: FFR is a gold standard used evaluate the severity of coronary artery lesions. QFR is a new non invasive technique for the same purpose based on the analysis of flow directly derived from routine coronary angiography, without additional intervention and with no induction of hyperemia. The aim was to compare the results obtained by QFR to those obtained by FFR in in terms of its predictive value. Method: Retrospective analysis of FFR measurements in routine coronary angiographic studies were compared to results obtained by means of QFR. Main left lesions were excluded. FFR was evaluated using pressure guides across the lesion under hyperemia induced by intracoronary or intravenous adenosine. Two orthogonal projections with no more than 25o difference between them were analyzed. The analysis was performed by two independent and operators blind to the results of FFR. The QAngioXA (Medis ®, Netherland) software was used in the analysis. Results: 35 coronary arteries were analyzed: LAD 57.1%, RCA 20.9%; Cx 20%. QFR was available for 27 arteries, the rest being discarded due to inadequate orientation of the artery. Mean QFR was 0.81 (SD 0.118). Mean difference between QFR and DD FFR was 0,04 (SD 0,006) (NS). Interobserver correlation was good (r=0.95, P 0.07). In only 7.4% of arteries there was a notable though not statistically significant difference between FFR and QFR, either due to under estimation or overestimation of lesion severity by QFR compared to FFR. Using FFR as a gold standard method QFR revealed sensitivity 90.9%, specificity 93.8%, The respective numbers for either positive or negative predictive values were the same. Area under the ROC curve was 0.923 (95% C.I. 0.01-1.00). Conclusion: this study reveals similar results of QFR compared to FFE in the estimation of coronary lesion severity. Given that QFR is a significantly less invasive and less expensive method than FFR, it may lead to an increased use of flow analysis in the determination of coronary artery lesion severity.

Performance Diagnóstica da FFR por Angiotomografia de Coronárias através de Software Baseado em Inteligência Artificial / Diagnostic Performance of a Machine Learning-Based CT-Derived FFR in Detecting Flow-Limiting Stenosis

Resumo Fundamento A quantificação não invasiva da reserva fracionada de fluxo miocárdico (FFR TC ) através de software baseado em inteligência artificial em versão mais atualizada e tomógrafo de última geração (384 cortes) apresenta elevada performance na detecção de isquemia coronariana. Objetivos Avaliar o desempenho diagnóstico da FFR TC na detecção de doença arterial coronariana (DAC) significativa em relação ao FFRi, em tomógrafos de gerações anteriores (128 e 256 cortes). Métodos Estudo retrospectivo com pacientes encaminhados à angiotomografia de artérias coronárias (TCC) e cateterismo (FFRi). Foram utilizados os tomógrafos Siemens Somatom Definition Flash (256 cortes) e AS+ (128 cortes). A FFR TC e a área luminal mínima (ALM) foram avaliadas em software (cFFR versão 3.0.0, Siemens Healthineers, Forchheim, Alemanha). DAC obstrutiva foi definida como TCC com redução luminal ≥50% e DAC funcionalmente obstrutiva como FFRi ≤0,8. Todos os valores de p reportados são bicaudais; e quando <0,05, foram considerados estatisticamente significativos. Resultados Noventa e três pacientes consecutivos (152 vasos) foram incluídos. Houve boa concordância entre FFR TC e FFRi, com mínima superestimação da FFR TC (viés: -0,02; limites de concordância: 0,14 a 0,09). Diferentes tomógrafos não modificaram a relação entre FFR TC e FFRi (p para interação = 0,73). A FFR TC demonstrou performance significativamente superior à classificação visual de estenose coronariana (AUC 0,93 vs. 0,61, p <0,001) e à ALM (AUC 0,93 vs. 0,75, p <0,001) reduzindo o número de casos falso-positivos. O melhor ponto de corte para a FFR TC utilizando um índice de Youden foi de 0,85 (sensiblidade, 87%; especificidade, 86%; VPP, 73%; NPV, 94%), com redução de falso-positivos. Conclusão FFR TC baseada em inteligência artificial, em tomógrafos de gerações anteriores (128 e 256 cortes), apresenta boa performance diagnóstica na detecção de DAC, podendo ser utilizada para reduzir procedimentos invasivos.

Abstract Background The non-invasive quantification of the fractional flow reserve (FFRCT) using a more recent version of an artificial intelligence-based software and latest generation CT scanner (384 slices) may show high performance to detect coronary ischemia. Objectives To evaluate the diagnostic performance of FFRCT for the detection of significant coronary artery disease (CAD) in contrast to invasive FFR (iFFR) using previous generation CT scanners (128 and 256- detector rows). Methods Retrospective study with patients referred to coronary artery CT angiography (CTA) and catheterization (iFFR) procedures. Siemens Somatom Definition Flash (256-detector rows) and AS+ (128-detector rows) CT scanners were used to acquire the images. The FFRCT and the minimal lumen area (MLA) were evaluated using a dedicated software (cFFR version 3.0.0, Siemens Healthineers, Forchheim, Germany). Obstructive CAD was defined as CTA lumen reduction ≥ 50%, and flow-limiting stenosis as iFFR ≤0.8. All reported P values are two-tailed, and when <0.05, they were considered statistically significant. Results Ninety-three consecutive patients (152 vessels) were included. There was good agreement between FFRCT and iFFR, with minimal FFRCT overestimation (bias: -0.02; limits of agreement:0.14-0.09). Different CT scanners did not modify the association between FFRCT and FFRi (p for interaction=0.73). The performance of FFRCT was significantly superior compared to the visual classification of coronary stenosis (AUC 0.93vs.0.61, p<0.001) and to MLA (AUC 0.93vs.0.75, p<0.001), reducing the number of false-positive cases. The optimal cut-off point for FFRCT using a Youden index was 0.85 (87% Sensitivity, 86% Specificity, 73% PPV, 94% NPV), with a reduction of false-positives. Conclusion Machine learning-based FFRCT using previous generation CT scanners (128 and 256-detector rows) shows good diagnostic performance for the detection of CAD, and can be used to reduce the number of invasive procedures.

The lesion characteristics and predictors of obstructive coronary artery disease with anatomy-function mismatch / 中华放射学杂志

Objective:To explore the lesion characteristics and predictors of invasive coronary angiography (ICA)-verified obstructive lesions with fractional flow reserve (FFR)>0.80, that is, anatomy-function mismatch.Methods:A total of 515 obstructive vessels in 419 coronary disease patients from 11 Chinese medical centers undergoing coronary CT angiography and ICA and FFR were retrospectively analyzed. All vessels had one target lesion with diameter stenosis ≥50 % by ICA. There were 229 vessels in the match group (FFR≤0.80) and 286 vessels in the mismatch group (FFR>0.80). The lesion characteristics including lesion territory, the distance of the coronary artery ostium to the proximal end of the lesion, minimum lumen area, reference lumen area, plaque length and burden, plaque volume and component volume, remodeling index and plaque morphological complexity were measured and compared between the two groups. Optimal thresholds of quantitative plaque characteristics were defined by Yoden index. Logistic regression analysis was used to analyze the predictors of anatomy-function mismatch. Area under receiver operating characteristic curve (AUC) was used to analyze the ability of different lesion features to predict mismatched lesions.Results:The coronary stenosis, plaque burden and length, plaque volume (including each component volume) in the mismatch group were smaller than those in the match group, and FFR, minimum lumen area were larger (all P<0.05). Left anterior descending artery (LAD) lesion and severe complex plaque were more common in the match group than the mismatch group with a statistically significant difference. Univariate logistic regression analysis showed that LAD lesion, minimum lumen area>4 mm 2, plaque burden and length, plaque calcification volume<27 mm 3, plaque lipid volume<30 mm 3, plaque fiber volume<150 mm 3 and plaque morphological complexity were predictiors of anatomic function mismatched lesions; Multivariate logistic regression showed that the minimum lumen area>4 mm 2 (OR=3.371, 95%CI 1.903-5.973, P<0.001), plaque lipid volume<30 mm 3 (OR=3.014, 95%CI 1.691-5.373, P<0.001), plaque morphological complexity (mild OR=17.772, 95%CI 8.072-39.128, P<0.001, moderate OR=6.383, 95%CI 3.739-10.896, P<0.001) were independent predictors of mismatched lesions. The AUC of the model based on the minimum lumen area, plaque lipid volume and morphological complexity was 0.824, which was superior to either of the plaque feature alone ( P<0.001). Conclusions:The minimum lumen area, lipid volume and plaque morphological complexity are independent predictors of the anatomical-functional mismatch lesions, and the combination can significantly improve the prediction value.