Differentiating Macrovascular and Microvascular Ischemia Using Fractal Analysis of Dynamic Myocardial Perfusion Stress-CT.

OBJECTIVES: Fractal analysis of dynamic myocardial stress computed tomography perfusion imaging (4D-CTP) has shown potential to noninvasively differentiate obstructive coronary artery disease (CAD) and coronary microvascular disease (CMD). This study validates fractal analysis of 4D-CTP in a multicenter setting and assesses its diagnostic accuracy in subgroups with ischemia and nonobstructed coronary arteries (INOCA) and with mild to moderate stenosis. MATERIALS AND METHODS: From the AMPLIFiED multicenter trial, patients with suspected or known chronic myocardial ischemia and an indication for invasive coronary angiography were included. Patients underwent dual-source CT angiography, 4D-CTP, and CT delayed-enhancement imaging. Coronary artery disease, CMD, and normal perfusion were defined by a combined reference standard comprising invasive coronary angiography with fractional flow reserve, and absolute or relative CT-derived myocardial blood flow. Nonobstructed coronary arteries were defined as ≤25% stenosis and mild to moderate stenosis as 26%-80%. RESULTS: In 127 patients (27% female), fractal analysis accurately differentiated CAD (n = 61, 23% female), CMD (n = 23, 30% female), and normal perfusion (n = 34, 35% female) with a multiclass area under the receiver operating characteristic curve (AUC) of 0.92 and high agreement (multiclass κ = 0.89). In patients with ischemia (n = 84), fractal analysis detected CAD (n = 61) over CMD (n = 23) with sensitivity of 95%, specificity of 74%, accuracy of 89%, and AUC of 0.83. In patients with nonobstructed coronary arteries (n = 33), INOCA (n = 15) was detected with sensitivity of 100%, specificity of 78%, accuracy of 88%, and AUC of 0.94. In patients with mild to moderate stenosis (n = 27), fractal analysis detected CAD (n = 19) over CMD with sensitivity of 84%, specificity of 100%, accuracy of 89%, and AUC of 0.95. CONCLUSIONS: In this multicenter study, fractal analysis of 4D-CTP accurately differentiated CAD and CMD including subgroups with INOCA and with mild to moderate stenosis.

Fractal Analysis of Dynamic Stress CT-Perfusion Imaging for Detection of Hemodynamically Relevant Coronary Artery Disease.

BACKGROUND: Combined computed tomography-derived myocardial blood flow (CTP-MBF) and computed tomography angiography (CTA) has shown good diagnostic performance for detection of coronary artery disease (CAD). However, fractal analysis might provide additional insight into ischemia pathophysiology by characterizing multiscale perfusion patterns and, therefore, may be useful in diagnosing hemodynamically significant CAD. OBJECTIVES: The purpose of this study was to investigate, in a multicenter setting, whether fractal analysis of perfusion improves detection of hemodynamically relevant CAD over myocardial blood flow quantification (CTP-MBF) using dynamic, 4-dimensional, dynamic stress myocardial computed tomography perfusion (CTP) imaging. METHODS: In total, 7 centers participating in the prospective AMPLIFiED (Assessment of Myocardial Perfusion Linked to Infarction and Fibrosis Explored with Dual-source CT) study acquired CTP and CTA data in patients with suspected or known CAD. Hemodynamically relevant CAD was defined as ≥90% stenosis on invasive coronary angiography or fractional flow reserve <0.80. Both fractal analysis and CTP-MBF quantification were performed on CTP images and were combined with CTA results. RESULTS: This study population included 127 participants, among them 61 patients, or 79 vessels, with CAD as per invasive reference standard. Compared with the combination of CTP-MBF and CTA, combined fractal analysis and CTA improved sensitivity on the per-patient level from 84% (95% CI: 72%-92%) to 95% (95% CI: 86%-99%; P = 0.01) and specificity from 70% (95% CI: 57%-82%) to 89% (95% CI: 78%-96%; P = 0.02). The area under the receiver-operating characteristic curve improved from 0.83 (95% CI: 0.75-0.90) to 0.92 (95% CI: 0.86-0.98; P = 0.01). CONCLUSIONS: Fractal analysis constitutes a quantitative and pathophysiologically meaningful approach to myocardial perfusion analysis using dynamic stress CTP, which improved diagnostic performance over CTP-MBF when combined with anatomical information from CTA.

Fractal analysis of 4D dynamic myocardial stress-CT perfusion imaging differentiates micro- and macrovascular ischemia in a multi-center proof-of-concept study.

Fractal analysis of dynamic, four-dimensional computed tomography myocardial perfusion (4D-CTP) imaging might have potential for noninvasive differentiation of microvascular ischemia and macrovascular coronary artery disease (CAD) using fractal dimension (FD) as quantitative parameter for perfusion complexity. This multi-center proof-of-concept study included 30 rigorously characterized patients from the AMPLIFiED trial with nonoverlapping and confirmed microvascular ischemia (nmicro = 10), macrovascular CAD (nmacro = 10), or normal myocardial perfusion (nnormal = 10) with invasive coronary angiography and fractional flow reserve (FFR) measurements as reference standard. Perfusion complexity was comparatively high in normal perfusion (FDnormal = 4.49, interquartile range [IQR]:4.46-4.53), moderately reduced in microvascular ischemia (FDmicro = 4.37, IQR:4.36-4.37), and strongly reduced in macrovascular CAD (FDmacro = 4.26, IQR:4.24-4.27), which allowed to differentiate both ischemia types, p < 0.001. Fractal analysis agreed excellently with perfusion state (κ = 0.96, AUC = 0.98), whereas myocardial blood flow (MBF) showed moderate agreement (κ = 0.77, AUC = 0.78). For detecting CAD patients, fractal analysis outperformed MBF estimation with sensitivity and specificity of 100% and 85% versus 100% and 25%, p = 0.02. In conclusion, fractal analysis of 4D-CTP allows to differentiate microvascular from macrovascular ischemia and improves detection of hemodynamically significant CAD in comparison to MBF estimation.

Diagnostic Performance of Dynamic Myocardial Perfusion Imaging Using Dual-Source Computed Tomography.

BACKGROUND: Single-center studies indicated a high diagnostic accuracy of dynamic computed tomography perfusion (CTP) imaging in the diagnosis of coronary artery disease (CAD). OBJECTIVES: This prospective multicenter study determined the diagnostic performance of combined coronary computed tomography angiography (CTA) and CTP for detecting hemodynamically significant CAD defined by invasive coronary angiography (ICA) with fractional flow reserve (FFR). METHODS: Seven centers enrolled 174 patients with suspected or known CAD who were clinically referred for ICA. CTA and dynamic CTP were performed using dual-source CT before ICA. FFR was done as part of ICA in the case of 26% to 90% coronary diameter stenosis. Hemodynamically significant stenosis was defined as FFR of <0.8 or >90% stenosis on ICA. RESULTS: The study protocol was completed in 157 participants, and hemodynamically significant stenosis was detected in 76 of 157 patients (48%) and 112 of 442 vessels (25%). According to receiver-operating characteristic curve analysis, adding dynamic CTP to CTA significantly increased the area under the curve from 0.65 (95% CI: 0.57-0.72) to 0.74 (95% CI: 0.66-0.81; P = 0.011) on the patient level, with decreased sensitivity (93% vs 72%; P < 0.001), improved specificity (36% vs 75%; P < 0.001), and improved overall accuracy (64% vs 74%; P < 0.001). CONCLUSIONS: In this prospective multicenter study on dynamic CTP, the combination of anatomic assessment with coronary CTA and functional evaluation with dynamic CTP allowed more accurate identification of hemodynamically significant CAD compared with CTA alone. However, the clinical significance of this approach needs to be further investigated, including its usefulness in improving prognosis. (Assessment of Myocardial Perfusion Linked to Infarction and Fibrosis Explored With Dual-Source CT [AMPLIFiED]; UMIN000016353).

Post-operative constrictive pericarditis complicated with lymphocytopenia and hypoglobulinemia.

A 71-year-old man who had a history of open chest surgery was admitted due to anasarca and bilateral pleural effusions. Although imaging modalities could not demonstrate any pericardial abnormalities, right-sided cardiac catheterization revealed 'dip and plateau' in diastolic pressure waveform. He was admitted frequently because of the episodic right-sided congestive heart failure and hypoproteinemia due to protein-losing enteropathy. The peripheral lymphocyte count and serum gamma-globulin concentration were gradually decreased, and finally showed lymphocytopenia and hypoglobulinemia. On the last admission, the patient showed extensive cellulitis on both legs, and he developed septicemia, and finally died due to septic shock. Post-mortem examination showed that both visceral and parietal layers of the pericardium adhered tightly with mediastinal fibrosis. This case report suggested that constrictive pericarditis should be considered even if there is a lack of typical abnormal pericardial imaging findings when patients have a history of open chest surgery and recurrent right-sided congestive heart failure. In addition, we should be aware of a serious outcome due to immune compromised conditions such as lymphocytopenia and dysglobulinemia in this disorder.

Reduced vascular compliance is associated with impaired endothelium-dependent dilatation in the brachial artery of patients with congestive heart failure.

BACKGROUND: Alterations in elastic properties and vascular structure of conduit vessels are important detrimental factors contributing to increased cardiac load and reduced tissue perfusion in patients with congestive heart failure (CHF). It has been demonstrated that endothelial function in the peripheral vasculature is impaired in this disorder, which may induce abnormal vascular elastic properties and remodeling. However, it remains unknown whether changes in vascular structure or mechanical properties are related to endothelial dysfunction in conduit arteries of patients with CHF. METHODS AND RESULTS: Twenty-five CHF patients with nonischemic heart disease and 20 sex/age-matched controls were enrolled. Brachial artery diameter, intima-media thickness (IMT), and vascular stiffness as represented by distensibility and compliance were determined using a high-frequency linear transducer attached to a high-quality ultrasound system. In addition, flow-mediated dilatation (FMD) after 5-minute forearm occlusion and sublingual nitroglycerin-induced dilatation (NTG) were measured in the brachial artery. Brachial arterial diameter was similar between CHF and controls; however, IMT and wall/lumen ratio were significantly greater in CHF patients than in controls (IMT, 0.37+/-0.01 versus 0.31+/-0.01 mm; wall/lumen, 18.7+/-0.8 versus 15.1+/-0.8%: both P<.01). In addition, vascular stiffness parameters were lower in CHF than in controls (distensibility; 1.09+/-0.14 versus 1.60+/-0.15%/kPa, P<.01: compliance; 0.17+/-0.02 versus 0.26+/-0.02 mm(2) kPa, P<.05). FMD and TNG were significantly reduced in CHF (both P<.001). Although stiffness parameters in CHF were not significantly correlated with vascular structure (ie, IMT, wall/lumen) or clinical parameters (ie, age, lipids, glucose, blood pressure), elastic parameters were significantly correlated with FMD (distensibility; r=0.579, P<.005: compliance; r=0.433, P<.05), but not with NTG. CONCLUSION: The present study found that, in limb muscle conduit artery in patients with CHF, there are hypertrophic remodeling and endothelial dysfunction-associated alterations in vascular wall elastic properties.