Wijnand J. Stuijfzand

Relative Flow Reserve Derived From Quantitative Perfusion Imaging May Not Outperform Stress Myocardial Blood Flow for Identification of Hemodynamically Significant Coronary Artery Disease

Background—Quantitative myocardial perfusion imaging is increasingly used for the diagnosis of coronary artery disease. Quantitative perfusion imaging allows to noninvasively calculate fractional flow reserve (FFR). This so-called relative flow reserve (RFR) is defined as the ratio of hyperemic myocardial blood flow (MBF) in a stenotic area to hyperemic MBF in a normal perfused area. The aim of this study was to assess the value of RFR in the detection of significant coronary artery disease. Methods and Results—From a clinical population of patients with suspected coronary artery disease who underwent oxygen-15–labeled water cardiac positron emission tomography and invasive coronary angiography, 92 patients with single- or 2-vessel disease were included. Intermediate lesions (diameter stenosis, 30%–90%; n=75) were interrogated by FFR. Thirty-eight (41%) vessels were deemed hemodynamically significant (>90% stenosis or FFR ⩽0.80). Hyperemic MBF, coronary flow reserve, and RFR were lower for vessels with a hemodynamically significant lesion (2.01±0.78 versus 2.90±1.16 mL·min−1·g−1; P<0.001, 2.27±1.03 versus 3.10±1.29; P<0.001, and 0.67±0.23 versus 0.93±0.15; P<0.001, respectively). The correlation between RFR and FFR was moderate (r=0.54; P<0.01). Receiver operator characteristic curve analysis showed an area under the curve of 0.82 for RFR, which was not significantly higher compared with that for hyperemic MBF and coronary flow reserve (0.76; P=0.32 and 0.72; P=0.08, respectively). Conclusions—Noninvasive estimation of FFR by quantitative perfusion positron emission tomography by calculating RFR is feasible, yet only a trend toward a slight improvement of diagnostic accuracy compared with hyperemic MBF assessment was determined.

The effect of shoe lacing on plantar pressure distribution and in-shoe displacement of the foot in healthy participants.

AIMS A proof of concept study to investigate the effect of shoe lacing on the plantar pressure distribution and in-shoe displacement of the foot during walking. METHODS Three randomized shoe-lacing conditions, which differed in lacing tightness (comfortable, loosened, and completely loose) were investigated in 20 healthy adults. On a 10-m walking test, plantar pressures were assessed with the Pedar(®)-X in-shoe measurement system. Perceived in-shoe displacement was scored on a numerical rating scale. RESULTS With respect to the pressure time integral statistically significant effects were found in the hallux, toes 2-5, first metatarsal head, and lateral midfoot regions. Post hoc comparison showed for the hallux: mean increase of 45.5 kPa s (95% confidence interval [CI]: 3.2-87.8 kPa s), and toes 2-5: mean increase of 23.5 kPa s (95% CI: 0.1-46.9 kPa s) between comfortably secured and completely loosened laces; lateral midfoot: mean decrease of -18.1 kPa s (95% CI: -31.5 to -4.8 kPa s) between comfortably secured and loosened laces. No significant effect was found on peak pressure, and average pressure. Participants reported a significant increase in heel slipping and in slipping back and forth of the foot as the laces were loosened. CONCLUSIONS Looser lacing techniques resulted in small peak and average plantar pressure changes (less than 3% and 6.5% respectively). Pressure time integral under the hallux and toes 2-5 increased 16.3% and 14.5% respectively, and perceived in-shoe displacement increased as compared to comfortably secured laces. These results suggest that diabetes patients should be advised to comfortably tighten their shoelaces during the whole day.

Myocardial perfusion imaging with PET

Noninvasive assessment of coronary artery disease remains a challenging task, with a large armamentarium of diagnostic modalities. Myocardial perfusion imaging (MPI) is widely used for this purpose whereby cardiac positron emission tomography (PET) is considered the gold standard. Next to relative radiotracer distribution, PET allows for measurement of absolute myocardial blood flow. This quantification of perfusion improves diagnostic accuracy and prognostic value. Cardiac hybrid imaging relies on the fusion of anatomical and functional imaging using coronary computed tomography angiography and MPI, respectively, and provides incremental value as compared with either stand-alone modality.

Prevalence of ischaemia in patients with a chronic total occlusion and preserved left ventricular ejection fraction.

Aims Previous studies on invasive assessment of collateral function in patients with a chronic total occlusion (CTO) have displayed only a limited increase in collateral flow and high occurrence of coronary steal during pharmacological stress. This could question the necessity for ischaemia testing prior to revascularization of CTOs in the presence of myocardial viability. The purpose of the present study was to determine the prevalence of perfusion impairments in patients with a CTO as assessed by [15O]H2O positron emission tomography (PET). Methods and results Seventy-six consecutive patients (60 men, 62 ± 10 years) with a documented CTO and preserved left ventricular ejection fraction (LVEF) were included. All patients underwent PET to assess (hyperaemic) myocardial blood flow (MBF) and coronary flow reserve (CFR). Collateral connection score was 0 in 7 (9%), 1 in 13 (17%), and 2 in 56 (74%) of the cases, with predominantly a high Rentrop grade (96% ≥2). MBF of the target area during hyperaemia was significantly lower when compared with the remote area (1.37 ± 0.37 vs. 2.63 ± 0.71 mL min-1 g-1, P < 0.001). Target to remote ratio during hyperaemia was on average 0.54 ± 0.13, and 73 (96%) patients demonstrated a significantly impaired target to remote ratio (≤0.75). Only 7 (9%) patients displayed a preserved CFR of ≥2.50, whereas coronary steal (CFR <1.0) was observed in 10 (13%) patients. Conclusions Even in the presence of angiographically well-developed collateral arteries, the vast majority of CTO patients with a preserved LVEF showed significantly impaired perfusion. These results suggest that collateral function during increased blood flow demand in viable myocardium is predominantly insufficient.

Value of Hybrid Imaging with PET/CT to Guide Percutaneous Revascularization of Chronic Total Coronary Occlusion

Chronic total coronary occlusions (CTO) are documented in approximately one fifth of diagnostic invasive coronary angiographies (ICA). Percutaneous coronary interventions (PCI) of CTO are challenging and are accompanied by higher complication and lower success rates in comparison with non-CTO PCI. Scrutinous evaluation of ischemia and viability to justify percutaneous revascularization is therefore of importance to select eligible patients for such a procedure. Furthermore, knowledge of the anatomical features of the occlusion may predict the chances of success of PCI CTO and could even guide the procedural strategy to augment the likelihood of recanalization. Positron emission tomography (PET) is unequivocally accepted as the reference standard for ischemia and viability testing, whereas coronary computed tomography angiography (CCTA) currently allows for non-invasive detailed three-dimensional imaging of the coronary anatomy that adds morphological information over two-dimensional ICA. Hybrid PET/CT could therefore be useful for optimal patient selection as well as procedural planning. This review discusses the potential value of PET/CT to guide PCI in CTOs.

Measurement of LV Volumes and Function Using Oxygen-15 Water-Gated PET and Comparison With CMR Imaging

Myocardial perfusion imaging using positron emission tomography (PET) is a valuable tool in the diagnosis of coronary artery disease. And although PET using [15O]H2O has a high diagnostic accuracy for predicting coronary artery disease in routine clinical practices [(1)][1], left ventricular (LV)

Comparative diagnostic accuracy of dual-energy CT myocardial perfusion imaging by monochromatic energy versus material decomposition methods

PURPOSE To compare the diagnostic value of monochromatic and material decomposition (MD) dual- energy computed tomography (DECT) imaging for the evaluation of ischemia. METHODS Patients with suspected coronary artery disease underwent rest-stress DECT and SPECT perfusion imaging. DECT images were reconstructed between 40 and 140keV and through MD of iodine/muscle. RESULTS MD and monochromatic imaging had a sensitivity, specificity, negative predictive, positive predictive value, and accuracy of 89%, 40%, 67%, 73% and 71%; and 91%, 67%, 67%, 91% and 86%, respectively (p=0.05). CONCLUSION DECT using monochromatic energy displayed a non-significantly higher diagnostic accuracy for myocardial ischemia as compared with DECT MD.

Influence of Symptom Typicality for Predicting MACE in Patients Without Obstructive Coronary Artery Disease: From the CONFIRM Registry (Coronary Computed Tomography Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry)

Our objective was to assess the prognostic value of symptom typicality in patients without obstructive coronary artery disease (CAD), determined by coronary computed tomographic angiography (CCTA). We identified 4215 patients without prior history of CAD and without obstructive CAD (<50% CCTA stenosis). CAD severity was categorized as nonobstructive (1%–49%) and none (0%). Based upon the Diamond‐Forrester criteria for angina pectoris, symptom typicality was classified as asymptomatic, nonanginal, atypical, and typical. Multivariable Cox proportional hazards models were used to assess the risk of major adverse cardiac events (MACE), comprising all‐cause mortality, myocardial infarction, unstable angina, and late revascularization, according to symptom typicality. Mean patient age was 57.0 ±12.0 years (54.9% male). During a median follow‐up of 5.3 years (interquartile range, 4.6–5.9 years), MACE were reported in 312 (7.4%) patients. Among patients with nonobstructive CAD, there was an association between symptom typicality and MACE (P for interaction = 0.05), driven by increased risk of MACE among those with typical angina and nonobstructive CAD (hazard ratio: 1.62, 95% confidence interval: 1.06–2.48, P = 0.03). No consistent relationship was found between symptom typicality and MACE among patients without any CAD (hazard ratio: 0.73, 95% confidence interval: 0.34–1.57, P = 0.08). In the CONFIRM registry, patients who presented with concomitant typical angina and nonobstructive CAD had a higher rate of MACE than did asymptomatic patients with nonobstructive CAD. However, the presence of typical angina did not appear to portend worse prognosis in patients with no CAD.

Impact of Revascularization on Absolute Myocardial Blood Flow as Assessed by Serial [15O]H2O Positron Emission Tomography Imaging: A Comparison With Fractional Flow Reserve

Background: The main goal of coronary revascularization is to restore myocardial perfusion in case of ischemia, causing coronary artery disease. Yet, little is known on the effect of revascularization on absolute myocardial blood flow (MBF). Therefore, the present prospective study assesses the impact of coronary revascularization on absolute MBF as measured by [15O]H2O positron emission tomography and fractional flow reserve (FFR) in patients with stable coronary artery disease. Methods and Results: Fifty-three patients (87% men, mean age 58.7±9.0 years) with suspected coronary artery disease were included prospectively. All patients underwent serial [15O]H2O positron emission tomography perfusion imaging at baseline and after revascularization by either percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery. FFR was routinely measured at baseline and directly post-PCI. After revascularization, regional rest and stress MBF improved from 0.77±0.16 to 0.86±0.25 mL/min/g and from 1.57±0.59 to 2.48±0.91 mL/min/g, respectively, yielding an increase in coronary flow reserve from 2.02±0.69 to 2.94±0.94 (P<0.01 for all). Mean FFR at baseline improved post-PCI from 0.61±0.17 to 0.89±0.08 (P<0.01). After PCI, an increase in FFR paralleled improvement in absolute myocardial perfusion as reflected by stress MBF and coronary flow reserve (r = 0.74 and r = 0.71, respectively, P<0.01 for both). PCI demonstrated a greater improvement of regional stress MBF as compared with coronary artery bypass graft surgery (1.14±1.11 versus 0.66±0.69 mL/min/g, respectively, P=0.02). However, patients undergoing bypass grafting had a more advanced stage of coronary artery disease and more incomplete revascularizations. Conclusion: Successful coronary revascularization has a significant and positive impact on absolute myocardial perfusion as assessed by serial quantitative [15O]H2O positron emission tomography. Notably, improvement of FFR after PCI was directly related to the increase in hyperemic MBF.

Quantitative measurement of lipid rich plaque by coronary computed tomography angiography: A correlation of histology in sudden cardiac death

BACKGROUND AND AIMS Recent advancements in coronary computed tomography angiography (CCTA) have allowed for the quantitative measurement of high-risk lipid rich plaque. Determination of the optimal threshold for Hounsfield units (HU) by CCTA for identifying lipid rich plaque remains unknown. We aimed to validate reliable cut-points of HU for quantitative assessment of lipid rich plaque. METHODS 8 post-mortem sudden coronary death hearts were evaluated with CCTA and histologic analysis. Quantitative plaque analysis was performed in histopathology images and lipid rich plaque area was defined as intra-plaque necrotic core area. CCTA images were analyzed for quantitative plaque measurement. Low attenuation plaque (LAP) was defined as any pixel < 30, 45, 60, 75, and 90 HU cut-offs within a coronary plaque. The area of LAP was calculated in each cross-section. RESULTS Among 105 cross-sections, 37 (35.2%) cross-sectional histology images contained lipid rich plaque. Although the highest specificity for identifying lipid rich plaque was shown with <30 HU cut-off (88.2%), sensitivity (e.g. 55.6% for <75 HU, 16.2% for <30 HU) and negative predictive value (e.g. 75.9% for <75 HU, 65.9% for <30 HU) tended to increase with higher HU cut-offs. For quantitative measurement, <75 HU showed the highest correlation coefficient (0.292, p = 0.003) and no significant differences were observed between lipid rich plaque area and LAP area between histology and CT analysis (Histology: 0.34 ± 0.73 mm2, QCT: 0.37 ± 0.71 mm2, p = 0.701). CONCLUSIONS LAP area by CCTA using a <75 HU cut-off value demonstrated high sensitivity and quantitative agreement with lipid rich plaque area by histology analysis.