A New Approach in Risk Stratification by Coronary CT Angiography.

For a decade, coronary computed tomographic angiography (CCTA) has been used as a promising noninvasive modality for the assessment of coronary artery disease (CAD) as well as cardiovascular risks. CCTA can provide more information incorporating the presence, extent, and severity of CAD; coronary plaque burden; and characteristics that highly correlate with those on invasive coronary angiography. Moreover, recent techniques of CCTA allow assessing hemodynamic significance of CAD. CCTA may be potentially used as a substitute for other invasive or noninvasive modalities. This review summarizes risk stratification by anatomical and hemodynamic information of CAD, coronary plaque characteristics, and burden observed on CCTA

Fractional flow reserve-guided management in stable coronary disease and acute myocardial infarction: recent developments

Coronary artery disease (CAD) is a leading global cause of morbidity and mortality, and improvements in the diagnosis and treatment of CAD can reduce the health and economic burden of this condition. Fractional flow reserve (FFR) is an evidence-based diagnostic test of the physiological significance of a coronary artery stenosis. Fractional flow reserve is a pressure-derived index of the maximal achievable myocardial blood flow in the presence of an epicardial coronary stenosis as a ratio to maximum achievable flow if that artery were normal. When compared with standard angiography-guided management, FFR disclosure is impactful on the decision for revascularization and clinical outcomes. In this article, we review recent developments with FFR in patients with stable CAD and recent myocardial infarction. Specifically, we review novel developments in our understanding of CAD pathophysiology, diagnostic applications, prognostic studies, clinical trials, and clinical guidelines

혈관 조영술 기반 정량적 유량비를 이용한 동맥경화반의 특성 및 임상 예후 예측

학위논문(박사) -- 서울대학교대학원 : 의과대학 의학과, 2022. 8. 구본권.서론: 심장혈관의 협착을 평가하고 중재 시술을 하는 가장 표준적인 평가 방법은 경피적 관상동맥 조영술이다. 관상 동맥 질환의 예후를 결정하는 가장 중요한 요소는 심근의 허혈 정도이며 이는 심근분획혈류 (fractional flow reserve, FFR)를 통해 확인할 수 있기에, FFR을 이용한 재관류 시술이 중등도의 혈관 협착이 있는 환자에서 표준 치료로 알려져 있다. 하지만 FFR 측정은 시술 시간이 길어지고, 충혈제를 사용해야 하고, 압력 철선을 사용하는 불편함이 있다. 혈관 조영술 기반 정량적 유량비 (Quantitative flow ratio, QFR)는 컴퓨터 유체역학 기술을 기반으로 하여 2개의 관동맥 조영술 영상을 가지고 관상동맥을 3차원 재건하고 혈류의 속도에 대한 정보를 더하여 기존에 침습적으로만 얻어낼 수 있었던 FFR의 값을 심혈관 조영술 영상만으로 구현해 내는 인공지능기술이다. 혈관내 초음파는 관상동맥 중재시술 하는 중에, 해부학적인 혈관 내 병변, 혈관 내 동맥경화반의 특성을 얻어낼 수 있는 도구이다. 이는 역시 침습적인 관동맥 중재술로 얻을 수 있는 정보이다. 아직 QFR 정보와 혈관내 초음파 정보와의 관계는 잘 알려진 바가 없어, 비침습적 QFR값과 혈관내 초음파 정보사이의 관계에 대해 알아보고자 한다. 뿐만 아니라 우리는 QFR을 구할 때 같이 얻을 수 있는 QFR 그래프에서 얻어낼 수 있는 인덱스로 환자에 있어 허혈과의 관계와 환자의 임상적 결과 사이의 관계도 확인하고자 한다. 방법: 기존의 전향적 연구인 FLAVOUR study는 1700명의 중등도 관상동맥 협착을 가진 환자들을 대상으로 무작위 배정하여 혈관내 초음파 기반의 관상동맥 중재술과 FFR기반 관상동맥 중재술의 2년 추적검사 결과를 바탕으로 하는 다기관, 전향적, 무작위 배정 임상 시험이다. 이 연구에 등록된 심혈관 조영술 중에 QFR 분석이 가능한 혈관을 검토하여 중앙 분석기관에서 QFR 분석을 시행하였다. QFR 값이 0.80 이하인 것을 혈역학적으로 유의미한 것으로 정의하였다. 혈관내 초음파 특성은 QFR 값 0.80 기준으로 두그룹간 비교하였다. Final QFR의 의미는 중재술을 하지 않은 환자에서는 진단적 관상동맥 조영술 영상에서 계산한 QFR값, 중재술을 시행한 환자는 시술 후 마지막 관상동맥 조영술 영상에서 얻은 QFR 값을 뜻한다. QFR 곡선 분석을 통해서 곡선 상방의 면적의 비율 (%area above the QFR curve, %AAC) 가 구해졌고 이는 곡선 위 면적/전체 면적 X 100 (%)으로 계산된다. 주가 되는 비교는 2차원적 정량적 관상동맥 조영술 (2D-quantitative coronary angiography, 2D-QCA)에서 확인되는 직경 협착에 비해 QFR 0.80이하가 FFR 0.80이하를 예측하는 정확성으로 하였고, 기존2D-QCA에서 얻은 직경 협착에 비해 QFR의 FFR 0.80 이하를 예측하는 Receiver Operating Characteristic Curve (ROC) 곡선의 면적 비교를 하였다. 혈관내 초음파군에서도 비슷한 방식으로 혈관내 초음파상의 해부학적인 협착, 불안정 동맥경화반을 예측하는 능력을 비교하였다. 일차 임상종료점은 2년째 까지의 사망, 목표혈관 관련 심근경색, 목표혈관 재개통술로 정의하였다. 결과: 최종적으로 QFR 분석이 가능한 혈관은 867개였다. 3D-QCA 직경 협착 50% 이상이 허혈을 예측하는 정확도는 52.2% 인 것에 비해, QFR 0.80 이하의 허혈 예측 정확도는 92.7% 였다. QFR의 FFR 0.80 이하를 예측하는 능력은 ROC 커브를 볼 때 2D-QCA에서 얻어진 데이터나, 3D-QCA에서 얻어진 데이터에 비해 AUC 면적이 컸다 (QFR: 0.973 vs. 2D QCA %DS: 0.738). QFR 0.80 이하인 군은 QFR 0.80을 초과하는 군에 비해 병변의 길이가 길고, 최소 내강 면적은 작고, 동맥경화반의 양이 많았다. 해부학적인 특성뿐만 아니라, 동맥경화반의 특성도 차이가 있었는데, QFR 0.80 이하인 군은 QFR 0.80을 초과하는 군에 비해 저음영 동맥경화반, 혼합 동맥경화반, 동맥경화반의 파열, 석회화 결절 및 양성 재형성의 비율이 높았고, 섬유성 동맥경화반의 비율은 낮았다. 다만QFR의 정확도는 목표병변의 길이가 35 mm이상으로 길어질 경우에 감소하는 경향을 보였다. 이런 미만성 병변에서 QFR에 %AACvessel 데이터를 추가할 경우에 FFR 0.80 이하를 예측하는 예측능이 호전되는 것을 확인하였다 (AUC: from 0.898 to 0.914; NRI: 0.886, p=0.011; IDI: 0.053, p=0.139). Final QFR 이 낮은 (<0.92) 군은 Final QFR 이 높은 군 (≥0.92)에 비해 일차 임상종료점 발생의 빈도가 높은 것을 확인할 수 있었다 (final QFR 낮은 군 vs. final QFR 높은 군: 4.7% vs. 1.5%; HR: 3.21; 95% CI: 1.17-8.84; p=0.017). 결론: QFR 0.80 이하인 군은 혈관내 초음파상 보이는 해부학적으로 심한 병변의 특성뿐 아니라, 혈관내 초음파상 확인되는 동맥경화반의 질적으로 나쁜 특성과도 관련이 있었다. QFR 데이터를 해부학적인 데이터에 추가하는 것은 혈관내 초음파상 해부학적인 협착 외에, 불리한 동맥경화반의 특성을 예측하는 데에 증분 가치가 있음을 확인하였다. 이것은 QFR 은 허혈뿐 아니라 동맥경화반의 나쁜 모양까지 예측하는 예측력이 있음을 뜻하는 것이다.Background and Objectives: Quantitative flow ratio (QFR) is novel methods for evaluating the fractional flow reserve (FFR) without the use of an invasive coronary pressure wire and pharmacologic hyperemic agent. However, the relationship between QFR and intravascular ultrasound (IVUS) data is undetermined. The aim of this study was to investigate the relationship between angiography-derived FFR and IVUS findings. Additionally, we would like to report whether the new index values obtained in QFR are helpful in predicting ischemia and the relationship between QFR and clinical outcomes in patients. Methods: All vessels enrolled in Fractional FLow Reserve And Intravascular ultrasound-guided Intervention Strategy for Clinical OUtcomes in Patients with InteRmediate Stenosis (FLAVOUR) trial were screened and analysed for QFR. Computation of QFR was performed offline by an independent core laboratory. The values of QFR ≤0.80 were considered hemodynamically significant, and IVUS characteristics were divided into two groups based on a QFR value of 0.80. The final QFR was the QFR value of diagnostic coronary angiography in patients without percutaneous coronary intervention (PCI) and the post PCI QFR value in patients who underwent PCI. The QFR pullback curve was analyzed, % area above the QFR pullback curve (%AAC) is defined as the percentage of the area above the QFR pullback curve (AAC) to the total area［AAC/total area × 100 (%)］. The primary comparison was per-vessel diagnostic performance as assessed by area under the receiver-operating characteristic curve (AUC) of QFR ≤0.80 versus %DS assessed by quantitative coronary angiography (QCA) for the diagnosis FFR of ≤0.80. Secondary comparison included diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for QFR and 3D QCA-derived % DS using invasive FFR as the reference standard. The predictive value of QFR data for the IVUS adverse characteristics was evaluated using the same method. The primary clinical endpoint of this study was target vessel failure (TVF) at 24 months after randomization, defined as composite of cardiac death, target vessel relation myocardial infarction, and target vessel revascularization. Results: A total of 867 vessels were able to perform QFR analysis. Per-vessel level diagnostic accuracies of QFR and 3D QCA-derived %DS ≥50% for prediction FFR ≤0.80 were 92.7%, and 52.2%, respectively. For predicting vessels with FFR ≤0.80, QFR index was superior to the visual assessment, 2D or 3D-QCA data. AUC was higher for QFR compared with 2D QCA-derived % diameter stenosis (AUC 0.973 versus AUC 0.738). Vessels with QFR ≤0.80 had a longer lesion length, smaller minimal lumen area and greater plaque burden compared to vessels with QFR ≥0.80. Coronary vessels with QFR ≤0.80 showed higher rates of attenuated plaque, calcified plaque, mixed plaque, plaque rupture, calcified nodule and positive remodeling and lower rates of fibrous plaque compared with those of QFR >0.80. The diagnostic accuracies of QFR for prediction IVUS anatomical stenosis and the adverse plaque characteristics were 79.0% and 59.3%, respectively. The accuracy of QFR was decreased in vessels with diffuse disease (lesion length ≥35mm). In diffuse disease, the addition of %AACvessel to contrast QFR demonstrated a tendency of improving the discrimination and reclassification of the vessels with FFR ≤0.80 (AUC from 0.898 to 0.914; NRI 0.886, p=0.011; IDI 0.053, p=0.139). The incidence of TVF at 2 years was higher in the low final QFR group (<0.92) compared with the high final QFR group (≥0.92) (low QFR vs. high QFR; 4.7% vs. 1.5%; HR: 3.21; 95% CI: 1.17-8.84; p=0.017). Conclusions: Lower QFR value was related to IVUS defined anatomical stenosis or IVUS defined adverse plaque. The addition of contrast QFR to anatomical data had an incremental value in discriminating FFR ≤0.80, anatomical stenosis assessed by IVUS, and adverse plaque characteristics. These findings suggested that QFR can predict not only ischemic lesions but also plaque characteristics.Abstract in English i List of Figures iv Contents vi Introduction 1 Materials and Methods 4 Results 18 Discussion 61 References 73 Abstract in Korean 85박

Diagnostic value of transmural perfusion ratio derived from dynamic CT-based myocardial perfusion imaging for the detection of haemodynamically relevant coronary artery stenosis

Objectives: To investigate the additional value of transmural perfusion ratio (TPR) in dynamic CT myocardial perfusion imaging for detection of haemodynamically significant coronary artery disease compared with fractional flow reserve (FFR). Methods: Subjects with suspected or known coronary artery disease were prospectively included and underwent a CT-MPI examination. From the CT-MPI time-point data absolute myocardial blood flow (MBF) values were temporally resolved using a hybrid deconvolution model. An absolute MBF value was measured in the suspected perfusion defect. TPR was defined as the ratio between the subendocardial and subepicardial MBF. TPR and MBF results were compared with invasive FFR using a threshold of 0.80. Results: Forty-three patients and 94 territories were analysed. The area under the receiver operator curve was larger for MBF (0.78) compared with TPR (0.65, P = 0.026). No significant differences were found in diagnostic classification between MBF and TPR with a territory-based accuracy of 77 % (67-86 %) for MBF compared with 70 % (60-81 %) for TPR. Combined MBF and TPR classification did not improve the diagnostic classification. Conclusions: Dynamic CT-MPI-based transmural perfusion ratio predicts haemodynamically significant coronary artery disease. However, diagnostic performance of dynamic CT-MPI-derived TPR is inferior to quantified MBF and has limited incremental value. Key Points: • The transmural perfusion ratio from dynamic CT-MPI predicts functional obstructive coronary artery disease• Performance of the transmural perfusion ratio is inferior to quantified myocardial blood flow• The incremental value of the transmural perfusion ratio is limite

Optimizing Non-Invasive Detection of Coronary Artery Disease and Effects of Advanced Interventional Techniques for Patients with Stable Coronary Artery Disease:It is All about Myocardial Perfusion

The aim of this thesis was to (1) further optimize non-invasive detection of hemodynamically significant coronary artery disease (CAD) with coronary computed tomography angiography (CCTA) and myocardial perfusion imaging (MPI) and to examine (2) the effect of implantation of the bioresorbable vascular scaffold (BVS) and (3) chronic total occlusion percutaneous coronary intervention (CTO PCI). Part I showed that angiographic characteristics such as volumetric measures as well as morphological aspects of atherosclerosis as assessed by CCTA are of interest when considering the hemodynamic consequences of atherosclerosis. These findings add to luminal stenosis grading alone and aid in increasing the diagnostic accuracy of CCTA to predict hemodynamically significant CAD determined by invasive FFR. The main results of Part II indicate that implantation of the BVS is feasible however no benefit with regard to myocardial perfusion is observed during hyperemia or cold pressor testing. These findings do not support the use of BVS instead of metallic DES, especially since large randomized trials have illustrated that there is an increased risk in scaffold thrombosis during the first three years. Still, long-term outcome (>3 years) has yet to become available. The results of the studies in Part III indicate that the vast majority of patients with a CTO have significantly impaired myocardial perfusion with great effect of successful CTO PCI on recovery of myocardial perfusion and decrease of ischemic burden. Patient selection for CTO PCI should be based on expected patient benefit rather than lesion complexity

Integration of patient-specific myocardial perfusion in CT-based FFR computations

Computed Tomography based Fractional Flow Reserve (FFRCT) is a non-invasive simulation based measure for diagnosing ischaemia causing arterial stenoses. One drawback of simulation based measures are the assumptions made that are usually based on population studies that may not apply to all patients. This study describes the fundamental characteristics to FFRCT simulations and how the simulations can be simplified where it can and where assumptions break down. The investigation starts with assessing whether the simulations can be simplified to a steady flow, whilst uncharacteristic of typical coronary blood flow, it was demonstrated that with regards to the diagnostic measures of FFR, and its variants dFFR or iFR, that steady flow was applicable, which reduces the complexity of the simulation, saving computational time and resources as well as removing uncertainty in the input assumptions.[1] The next phase of the study explored the downstream conditions of the FFRCT simulation scheme. The microvasculature is too small to resolve in CT imaging and therefore assumptions are made regarding its form and function. Whilst form function relationships of the microvasculature are well established in the literature for the structure of microvessels at rest, assumptions regarding stress or hyperaemia are used for FFRCT to simulate maximal blood flow through the coronary arteries. The investigation utilised perfusion imaging to assess the validity of this assumption and showed how variable the microvascular response to hyperaemia is, and the effect that has on FFRCT.[2][3] The last part of the study produced a novel method of estimating the microvascular response using patient metrics such as age, sex, diabetes, smoker status etc, from a training dataset of 101 patients. By using the patient-specific microvascular response, FFRCT simulations better represent the coronary artery health of the patient. On a separate dataset of 10 patients, the FFRCT measurements using this novel method was also validated against the gold standard invasive FFR and has demonstrated a better diagnostic performance (94% accuracy) than the conventional method (82% accuracy). Secondly the novel method also created a probabilistic spread of FFRCT values that may provide better utility than a strict binary measure. Whilst this novel method will require further validation with larger studies, it nevertheless has potential to address some of the current drawbacks of FFRCT methods when applied to a varied patient demographic

Non-invasive detection and assessment of coronary stenosis from blood mean residence times.

Coronary artery stenosis is an abnormal narrowing of a coronary artery caused by an atherosclerotic lesion that reduces lumen space. Fractional flow reserve (FFR) is the gold standard method to determine the severity of coronary stenosis based on the determination of rest and hyperemic pressure fields, but requires an invasive medical procedure. Normal FFR is 1.0 and FFR RT, to account for varying volume and flow rate of individual segments. BloodRT was computed in 100 patients who had undergone the pressure-wire FFR procedure, and a threshold for BloodRT was determined to assess the physiological significance of a stenosis, analogous to the diagnostic threshold for FFR. The threshold exhibited excellent discrimination in detecting significant from non-significant stenosis compared to the gold standard pressure-wire FFR, with sensitivity of 98% and specificity of 96%. When applied to clinical practice, this could potentially allow practicing cardiologists to accurately assess and quantify the severity of coronary stenosis without resorting to invasive catheter-based techniques. The first 100 patient study required a clinically determined blood flow rate as a key model input. To create a more non-invasive process, a multiple linear regression approach was employed to determine blood flow rate entering a given artery segment. To validate this method, BloodRT was computed for a new set of 100 patients using the regression derived blood flow rate. The sensitivity and specificity were 95% and 97%, respectively, indicating similar discrimination compared to the clinically derived flow rate. The method was also applied to a succession of stenosis in series. When BloodRT of each individual stenosis was well above the threshold for significance, the cumulative effect of all stenoses led to an overall BloodRT below the threshold of hemodynamic significance