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

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

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

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

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

The ability of contemporary cardiologists to judge the ischemic impact of a coronary lesion visually

BACKGROUND: Landmark trials showed that invasive pressure measurement (Fractional Flow Reserve, FFR) was a better guide to coronary stenting than visual assessment. However, present-day interventionists have benefited from extensive research and personal experience of mapping anatomy to hemodynamics. AIMS: To determine if visual assessment of the angiogram performs as well as invasive measurement of coronary physiology. METHODS: 25 interventional cardiologists independently visually assessed the single vessel coronary disease of 200 randomized participants in The Objective Randomized Blinded Investigation with optimal medical Therapy of Angioplasty in stable angina trial (ORBITA). They gave a visual prediction of the FFR and Instantaneous Wave-free Ratio (iFR), denoted vFFR and viFR respectively. Each judged each lesion on 2 occasions, so that every lesion had 50 vFFR, and 50 viFR assessments. The group consensus visual estimates (vFFR-group and viFR-group) and individual cardiologists' visual estimates (vFFR-individual and viFR-individual) were tested alongside invasively measured FFR and iFR for their ability to predict the placebo-controlled reduction in stress echo ischemia with stenting. RESULTS: Placebo-controlled ischemia improvement with stenting was predicted by vFFR-group (p < 0.0001) and viFR-group (p < 0.0001), vFFR-individual (p < 0.0001) and viFR-individual (p < 0.0001). There were no significant differences between the predictive performance of the group visual estimates and their invasive counterparts: p = 0.53 for vFFR vs FFR and p = 0.56 for viFR vs iFR. CONCLUSION: Visual assessment of the angiogram by contemporary experts, provides significant additional information on the amount of ischaemia which can be relieved by placebo-controlled stenting in single vessel coronary artery disease.

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

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.

Comparison of a known invasive physiological method used for the evaluation of ischemia and a newer noninvasive physiological method for the same propose

INTRODUCTION: FFR is the most validated method for evaluating the physiological significance of non-occlusive coronary stenosis. FFR is the ratio of distal pressure (Pd) and aortic pressure (Pa) determined during adenosine induced hyperemia. Nonhyperemic pressure ratios were later introduced and validated against FFR, being non-inferior on ischemia detection. New methods for non-invasive physiological evaluation of ischemia recently became available for our daily practice. The Murray law-based QFR (µQFR or µFR) is a novel computational software that enables accurate estimation of FFR based on the analysis of a single angiographic projection with the adequate quality adjusting both the reference vessel diameter and the outgoing flow through side branches according to fractal geometry. Objective: Both methods were compared and validated against FFR with non-inferiority, it´s to our understanding that both methods can be compared and have similar results. Our objective is to compare the invasive evaluation of coronary physiology with RFR with this novel non-invasive method µFR. METHODS: We revised data from 04/2022 to 04/2023 and found more than 100 RFR evaluations in patients that underwent coronary angiography and presented a non-occlusive coronary lesion. From those we selected 73 patients, based on RFR values of less than 0.95 and used the angiography of the procedure for the evaluation of ischemia with this new software. Once we calculated the µFR we compared the results(positive or negative) to the RFR results. We used Qui square test for the analysis. RESULT: From 73 patients, 50 RFR were positive for ischemia and 34 µFR were positive for ischemia. From those 50 RFR positives for ischemia, 36 underwent PCI or CABG for revascularization. The remaining patients had a value close to 0.89 or had a diffuse pattern without any focal lesion that would benefit from revascularization. The concordance was made with Qui Square Test that confirms the non concordance of both methods in the selected population. Qui square test was 23. On the 16 cases that werent treated or had negative µFR, most had a diffuse CAD pattern, and the method did not had an impact on the decision on treatment. CONCLUSION: In our comparison of RFR vs µFR in 73 patients in the last year we found that there is a non concordance between RFR and µFR as methods evaluating ischemia in this selected small group. The differences can be seen in 16 patients were diffuse pattern was observed.

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

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.

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.

Anomalous aortic origin of the left coronary artery.

We present an unusual case of an anomalous left coronary artery arising from the contralateral sinus of Valsalva: a 63-year-old male patient who consulted to our emergency department with 1-week history of progressive dyspnea on exertion with clinical signs of heart failure, associated with lung congestion on the chest X ray and elevated NT-proBNP levels (2000 pg/ml; normal value <150). Doppler echocardiography showed severe dilation of both left atrium and left ventricle, with severe deterioration of LV systolic function (Ejection fraction of 26%), global hypokinesia and a moderate mitral regurgitation with central jet. A cardiac catheterization was performed, which evidenced an anomalous origin of the left main coronary artery from the right coronary sinus with a proximal lesion of nearly 50%. A coronary computed tomographic angiography confirmed the diagnosis of an anomalous origin with an intramyocardial path at the level of the interventricular septum, associated with moderate extrinsic compression. To determine the degree of functional ischemia presented by the left main coronary artery lesion we performed a fractional flow reserve evaluation, resulting in 0.75, which was ranked as significant. An angioplasty with implantation of a drug-eluting stent (with Everolimus) was performed successfully to the target lesion. The patient evolved favorably during hospitalization and was discharged from the medical center to continue outpatient follow-up. Patient remained asymptomatic at 1-month and 6 months, during clinical evaluation, without evidence of ischemia on noninvasive functional assessment.

Presentamos un raro caso de nacimiento anómalo de arteria coronaria izquierda en el seno de Valsalva contralateral. Se trata de un hombre de 63 años que consultó al servicio de emergencias de nuestro centro por disnea progresiva de una semana de evolución, con signos clínicos de insuficiencia cardíaca, asociado a signos de congestión en la radiografía de tórax, y valores de NT-proBNP elevados (2000 pg/ml; valor normal <150). El ecocardiograma Doppler evidenció dilatación grave de la aurícula y del ventrículo izquierdo, con deterioro grave de la función sistólica (fracción de eyección de 26%), hipoquinesia global e insuficiencia mitral moderada con jet central. Se realizó una cinecoronariografía que evidenció el nacimiento anómalo del tronco de arteria coronaria izquierda desde el seno coronario derecho, con una lesión cercana al 50%. Una angiotomografía coronaria confirmó el origen anómalo del vaso coronario, con trayecto intramiocárdico a nivel del septum interventricular asociado a compresión extrínseca moderada. Para determinar el grado de isquemia funcional que presentaba la lesión del tronco coronario izquierdo se evaluó la reserva de flujo fraccional, que arrojó un resultado de 0.75 el cual se consideró significativo, prosiguiendo a angioplastia con implante de stent liberador de droga (con Everolimus) a dicha lesión. El paciente evolucionó favorablemente durante la internación en el hospital, egresando de la institución para continuar seguimiento ambulatorio. Persistió asintomático en los controles realizados al mes y a los 6 meses, sin evidencia de isquemia en la evaluación funcional no invasiva.

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.

Angiography quantitative flow ratio: a systematic review and analysis of diagnostic accuracy

INTRODUCTION: Fractional flow reserve (FFR) is the gold standard to evaluate severity of coronary stenosis. Quantitative flow ratio (QFR) is a new angiography-based method used to infer FFR. Studies have shown >90% agreement between QFR and FFR. OBJECTIVE: To conduct a systematic review and diagnostic accuracy analysis of QFR using individual vessel data. METHODS: This review follows PRISMA guidelines. MEDLINE, EMBASE and Cochrane Library of Clinical Trials were searched for QFR accuracy studies published until Oct 2020. Inclusion criteria: (a) QFR vs FFR; (b) QFR diagnostic capacity; (c) agreement data between QFR/FFR expressed as dot plots or individual data tables. Graphic data were digitized using a semiautomatic software. QFR/FFR values were dichotomized using cutoff values of ≤ 0.80 for ischemia. QFR diagnostic accuracy was assessed by two logistic regressions superimposed on the same graph to ensure the probability of agreement between QFR and FFR for any QFR value. FFR was the reference standard. RESULTS: 20 studies comprising 5,318 vessels from 4,429 patients were included. Most patients were male (64%) at an age of 66.8 ± 5.2 years. Figure 1A shows FFR distribution and QFR diagnostic accuracy for different QFR ranges. QFR overall accuracy, sensitivity, specificity, PPV and NPV are displayed in Figure 1B. A diagnostic accuracy of 87% was reached for QFR cutoff values 0.86, and 95% or 98% with cutoffs 0.91 and 0.94, respectively (Figure 1B). CONCLUSIONS: A very good diagnostic accuracy of QFR measures was observed using individual vessel data. QFR can be used to evaluate the severity of coronary stenosis. At less accurate values addition of FFR can improve precision.

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

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.

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.

Offline Assessment of the Quantitative Flow Ratio: Is it Useful in Clinical Practice?

INTRODUCTION: Fractional flow reserve (FFR) has been established as the gold standard in the physiological assessment of coronary obstructions severity. However, the need to insert an intracoronary pressure guidewire is a factor that limits its use. Quantitative flow ratio (QFR) is a method that infers the value of FFR from 3-dimensional quantitative coronary angiography (3D-QCA), eliminating the use of a pressure wire and coronary hyperemia. The present study aims to evaluate the diagnostic accuracy of QFR and 3D-QCA in comparison with FFR for the identification of significant obstructive coronary lesions (FFR ≤.80) and the feasibility to assess QFR in a cohort of patients without dedicated angiographic acquisition. METHODS: Consecutive patients with coronary angiography with moderate obstructive lesions that had previous FFR measurement were evaluated. Validation of QFR was assessed by the area under the curve (AUC) and other statistical tools, using FFR as the reference method. RESULTS: Seventy-five arteries from 69 patients were evaluated. The accuracy of the QFR to detect FFR ≤.80 was 84.0% (95% confidence interval, 75.6-92.4). The correlation and agreement between FFR and QFR were r=0.54 (P<.01) and mean difference was -0.02 ± 0.09 (P=.09), respectively. The AUC of QFR and 3D-QCA identifying stenosis >50% was 0.854 and 0.755, respectively (P=.09). CONCLUSION: QFR demonstrated good accuracy compared with FFR for the assessment of moderate obstructive coronary lesions in an unselected clinical practice population. However, many patients were excluded from the analysis and there was no statistical difference between the receiver operator characteristic curves of the QFR and percent diameter stenosis.

Bone Marrow Cells Improve Coronary Flow Reserve in Ischemic Nonrevascularized Myocardium: A MiHeart/IHD Quantitative Perfusion CMR Substudy.

OBJECTIVES: This study investigated whether intramyocardial bone marrow-derived hematopoietic progenitor cells (BMCs) increase coronary flow reserve (CFR) in ischemic myocardial regions where direct revascularization was unsuitable. BACKGROUND: Patients with diffuse coronary artery disease frequently undergo incomplete myocardial revascularization, which increases their risk for future adverse cardiovascular outcomes. The residual regional ischemia related to both untreated epicardial lesions and small vessel disease usually contributes to the disease burden. METHODS: The MiHeart/IHD study randomized patients with diffuse coronary artery disease undergoing incomplete coronary artery bypass grafting to receive BMCs or placebo in ischemic myocardial regions. After the procedure, 78 patients underwent cardiovascular magnetic resonance (CMR) at 1, 6, and 12 months and were included in this cardiac magnetic resonance substudy with perfusion quantification. Segments were classified as target (injected), adjacent (surrounding the injection site), and remote from injection site. RESULTS: Of 1,248 segments, 269 were target (22%), 397 (32%) adjacent, and 582 (46%) remote. The target had significantly lower CFR at baseline (1.40 ± 0.79 vs 1.64 ± 0.89 in adjacent and 1.79 ± 0.79 in remote; both P < 0.05). BMCs significantly increased CFR in target and adjacent segments at 6 and 12 months compared with placebo. In target regions, there was a progressive treatment effect (27.1% at 6 months, P = 0.037, 42.2% at 12 months, P = 0.001). In the adjacent segments, CFR increased by 21.8% (P = 0.023) at 6 months, which persisted until 12 months (22.6%; P = 0.022). Remote segments in both the BMC and placebo groups experienced similar improvements in CFR (not significant at 12 months compared with baseline). CONCLUSIONS: BMCs, injected in severely ischemic regions unsuitable for direct revascularization, led to the largest CFR improvements, which progressed up to 12 months, compared with smaller but persistent CFR changes in adjacent and no improvement in remote segments.

Frequency-Following Response (FFR) in cochlear implant users: a systematic review of acquisition parameters, analysis, and outcomes. / Frequency-Following Response (FFR) em usuários de implante coclear: uma revisão sistemática dos parâmetros de aquisição, análise e resultados.

PURPOSE: To characterize the acquisition parameters, analysis, and results of the frequency-following response (FFR) in cochlear implant users. RESEARCH STRATEGIES: The search was conducted in Cochrane Library, Latin American and Caribbean Health Sciences Literature (LILACS), Ovid Technologies, PubMed, SciELO, ScienceDirect, Scopus, Web of Science, and gray literature. SELECTION CRITERIA: Studies on FFR in cochlear implant users or that compared them with normal-hearing people, with no restriction of age, were included. Secondary and experimental studies were excluded. There was no restriction of language or year of publication. DATA ANALYSIS: The data were analyzed and reported according to the stages in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), 2020. The methodological quality was analyzed with the Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross-Sectional Studies. Divergences were solved by a third researcher. RESULTS: Six studies met the inclusion criteria. Only one study was comparative, whose control group comprised normal-hearing people. The variations in acquisition parameters were common and the analysis predominantly approached the time domain. Cochlear implant users had different FFR results from those of normal-hearing people, considering the existing literature. Most articles had low methodological quality. CONCLUSION: There is no standardized FFR acquisition and analysis protocol for cochlear implant users. The results have a high risk of bias.

OBJETIVO: Caracterizar os parâmetros de aquisição, análise e resultados do exame Frequency Following Response (FFR) em usuários de implante coclear. ESTRATÉGIA DE PESQUISA: As buscas foram realizadas nas bases Cochrane Library, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Ovid Technologies, PubMed, SciELO, ScienceDirect, Scopus, Web of Science e na literatura cinzenta. CRITÉRIOS DE SELEÇÃO: Foram incluídos estudos sobre o FFR em usuários de implante coclear ou que os comparassem à indivíduos com audição normal, sem restrição de idade. Foram excluídos estudos secundários e experimentais. Não houve restrição de idioma e ano de publicação. ANÁLISE DOS DADOS: Os dados foram analisados e redigidos de acordo com as etapas do Preferred Reporting Items for Systematic Reviews and Meta-Analyse (PRISMA) 2020. Para análise da qualidade metodológica foi utilizado o instrumento Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross Sectional Studies. As divergências foram resolvidas por um terceiro pesquisador. RESULTADOS: Seis estudos atenderam aos critérios de inclusão. Apenas um estudo foi do tipo comparativo com grupo controle de indivíduos com audição normal. As variações nos parâmetros de aquisição foram comuns e as análises predominaram no domínio do tempo. Usuários de implante coclear apresentaram diferenças nos resultados do FFR quando comparados a indivíduos com audição normal, considerando a literatura existente. A maioria dos artigos teve baixa qualidade metodológica. CONCLUSÃO: Não existe padronização de um protocolo de aquisição e análise para o FFR em usuários de implante coclear. Os resultados são de alto risco de viés.

Feasibility of coronary blood flow simulations using mid-fidelity numeric and geometric models.

The fractional flow reserve index (FFR) is currently used as a gold standard to quantify coronary stenosis's functional relevance. Due to its highly invasive nature, the development of noninvasive surrogates based on simulations has drawn much attention in recent years, emphasizing efficient strategies that enable translational research. The focus of this work is twofold. First, to assess the feasibility of using a mid-fidelity numerical strategy (transversally enriched pipe element method, TEPEM), placed between low- and high-fidelity models, for the estimation of flow-related quantities, such as FFR and wall shear stress (WSS). Low-fidelity models, as zero- or one-dimensional models, are computationally inexpensive but in detriment of poorer spatially detailed predictions. On the other hand, high-fidelity models, such as classical three-dimensional numerical approximations, can provide detailed predictions but their transition to clinical application is prohibitive due to high computational costs. As a second goal, we quantify the impact of the length of lateral branches in the blood flow through the interrogated vessel of interest to further reduce the computational burden. Both studies are addressed considering a cohort of 17 coronary geometries. A total of 20 locations were selected to estimate the FFR index for a wide range of Coronary Flow Reserve (CFR) scenarios. Numerical results suggest that the mid-fidelity TEPEM model is a reliable approach for the efficient estimation of the FFR index and WSS, with an error in the order of [Formula: see text] and [Formula: see text], respectively, when compared to the high-fidelity prediction. Moreover, such mid-fidelity models require much less computational resources, in compliance with infrastructure frequently available in the clinic, by achieving a speedup between 30 and 60 times compared to a conventional finite element approach. Also, we show that shortening peripheral branches does not introduce considerable perturbations either in the flow patterns, in the wall shear stress, or the pressure drop. Comparing the different geometric models, the error in the estimation of FFR index and WSS is reduced to less than [Formula: see text] and [Formula: see text], respectively.

Functional Coronary Artery Assessment: a Systematic Literature Review.

Cardiovascular diseases represent the number one cause of death in the world, including the most common disorders in the heart's health, namely coronary artery disease (CAD). CAD is mainly caused by fat accumulated in the arteries' internal walls, creating an atherosclerotic plaque that impacts the blood flow functional behavior. Anatomical plaque characteristics are essential but not sufficient for a complete functional assessment of CAD. In fact, plaque analysis and visual inspection alone have proven insufficient to determine the lesion severity and hemodynamic repercussion. Furthermore, the fractional flow reserve (FFR) exam, which is considered the gold standard for stenosis functional impair determination, is invasive and contains several limitations. Such a panorama evidences the need for new techniques applied to image exams to improve CAD functional assessment. In this article, we perform a systematic literature review on emerging methods determining CAD significance, thus delivering a unique base for comparing these methods, qualitatively and quantitatively. Our goal is to guide further studies with evidence from the most promising methods, highlighting the benefits from both areas. We summarize benchmarks, metrics for evaluation, and challenges already faced, thus shedding light on the requirements for a valid, meaningful, and accepted technique for functional assessment evaluation. We create a base of comparison based on quantitative and qualitative indicators and highlight the most relevant geometrical metrics that correlate with lesion significance. Finally, we point out future benchmarks based on recent literature.

Solution for Interference in Hotspot Scenarios Applying Q-Learning on FFR-Based ICIC Techniques.

This work explores interference coordination techniques (inter-cell interference coordination, ICIC) based on fractional frequency reuse (FFR) as a solution for a multi-cellular scenario with user concentration varying over time. Initially, we present the problem of high user concentration along with their consequences. Next, the use of multiple-input multiple-output (MIMO) and small cells are discussed as classic solutions to the problem, leading to the introduction of fractional frequency reuse and existing ICIC techniques that use FFR. An exploratory analysis is presented in order to demonstrate the effectiveness of ICIC techniques in reducing co-channel interference, as well as to compare different techniques. A statistical study was conducted using one of the techniques from the first analysis in order to identify which of its parameters are relevant to the system performance. Additionally, another study is presented to highlight the impact of high user concentration in the proposed scenario. Because of the dynamic aspect of the system, this work proposes a solution based on machine learning. It consists of changing the ICIC parameters automatically to maintain the best possible signal-to-interference-plus-noise ratio (SINR) in a scenario with hotspots appearing over time. All investigations are based on ns-3 simulator prototyping. The results show that the proposed Q-Learning algorithm increases the average SINR from all users and hotspot users when compared with a scenario without Q-Learning. The SINR from hotspot users is increased by 11.2% in the worst case scenario and by 180% in the best case.

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.