Impaired Myocardial Flow Reserve Research Articles

Significant Association of Serum Albumin With the Severity of Coronary Microvascular Dysfunction Using Dynamic CZT-SPECT.

Both low serum albumin (SA) concentration and coronary microvascular dysfunction (CMD) are risk factors for the development of heart failure (HF). We hypothesized that SA concentration is associated with myocardial flow reserve (MFR) and implicated in pathophysiological mechanism of HF. We retrospectively studied 454 patients undergoing dynamic cardiac cadmium-zinc-telluride myocardial perfusion imaging from April 2018 to February 2020. The population was categorized into three groups according to SA level (g/dL): Group 1: >4, Group 2: 3.5-4, and Group 3: <3.5. Myocardial blood flow (MBF) and myocardial flow reserve (MFR, defined as stress/rest MBF ratio) were compared. The mean age of the whole cohort was 66.2 years, and 65.2% were men. As SA decreased, stress MBF (mL min-1 g-1) and MFR decreased (MBF: 3.29 ± 1.03, MFR: 3.46 ± 1.33 in Group 1, MBF: 2.95 ± 1.13, MFR: 2.51 ± 0.93 in Group 2, and MBF: 2.64 ± 1.16, MFR: 1.90 ± 0.50 in Group 3), whereas rest MBF (mL min-1 g-1) increased (MBF: 1.05 ± 0.42 in Group 1, 1.27 ± 0.56 in Group 2, and 1.41 ± 0.61 in Group 3). After adjusting for covariates, compared with Group 1, the odds ratios for impaired MFR (defined as MFR < 2.5) were 3.57 (95% CI: 2.32-5.48) for Group 2 and 34.9 (95% CI: 13.23-92.14) for Group 3. The results would be similar if only regional MFR were assessed. The risk prediction for CMD using SA was acceptable, with an AUC of 0.76. Low SA concentration was associated with the severity of CMD in both global and regional MFR as well as MBF.

Impaired myocardial flow reserve from 82-rubidium positron emission tomography predicts survival benefit from revascularization: a multicenter registry study

Abstract Background The identification of patients that may accrue prognostic benefit from revascularization is complex. Myocardial perfusion imaging (MPI) using 82-rubidium positron emission tomography (82Rb-PET) provides information on myocardial perfusion defects, calcium-score, left ventricular ejection fraction (LVEF), and myocardial flow reserve (MFR). Purpose To examine if MFR assessed by 82-Rb PET MPI identifies subgroups that benefit from revascularization. Methods We included 7462 all-comers suspected of coronary artery disease undergoing 82-Rb-PET MPI at three high-volume nuclear centers in Denmark between January 1, 2018, and August 20, 2020. Patients with reversible perfusion defects &amp;lt;5%, eGFR &amp;lt;30 mL/min/1.73m2, receiving dialysis, left ventricular ejection fraction &amp;lt;35%, and those that died within 90 days of their index 82Rb-PET MPI were excluded. Revascularization was defined as percutaneous coronary intervention (PCI) or coronary artery bypass-graft surgery (CABG) within 90 days of MPI. Patients were followed for major adverse cardiac events (MACE), a composite of all-cause death, acute coronary syndromes, ischemic stroke, or heart failure, and all-cause mortality until July 9, 2022. We analyzed each outcome according to revascularization and MFR (&amp;lt;2 vs. ≥2) using the Kaplan-Meier estimator and proportional hazards Cox regressions adjusted for patient and 82Rb-PET characteristics, including any perfusion defects, using inverse probability weighting. Results A total of 1805 patients were included (mean age 69 (SD 10.6), 29.8% females, 27% diabetes), of whom 902 (50%) had MFR &amp;lt;2. The median follow-up was 35.9 months. A total of 480 were revascularized. 58 experienced a MACE; 36 died. Revascularization was associated with a significantly lower risk of all-cause mortality and MACE among patients with MFR&amp;lt;2, whereas there was no survival benefit from revascularization among those with normal MFR (figure 1). After adjustment, HR for revascularization for MACE in the MFR&amp;lt;2 group was 0.51 (95%CI 0.33-0.78) versus 1.19 (95%CI 0.64-2.20) in the MFR&amp;gt;=2 group (p for interaction 0.042) and for All-cause mortality 0.48 (95%CI 0.30-0.77) in the MFR&amp;lt;2 group versus 1.01 (95%CI 0.43-2.39) in the MFR&amp;gt;=2 group (p for interaction 0.28). Results were independent of the extent of reversible perfusion defect, consistent across several subgroups, and independent of the mode of revascularization (CABG or PCI), figure 2. Conclusion In this observational study, revascularization was associated with improved prognosis, specifically among patients with impaired MFR, whereas among patients with normal MFR, there was no prognostic benefit. Impaired MFR may identify patients with prognostic benefit from revascularization. This novel hypothesis should be tested in a randomized controlled trial.Kaplan MeierForest plot

Abstract 15719: Prognostic Interplay Between Myocardial Flow Reserve and Left Ventricular Ejection Fraction

Introduction: Myocardial flow reserve (MFR), measured using positron emission tomography (PET), has been shown to add incremental prognostic value in multiple patient populations. Whether this association is modified by left ventricular ejection fraction (LVEF) is not well studied. The aim of this analysis is to determine whether there is a prognostic interplay between myocardial flow reserve and LVEF. Methods: The study population included patients who had clinically indicated PET myocardial perfusion imaging and were prospectively followed for incident events. MFR was calculated as the ratio of stress to rest myocardial blood flow (MBF) (ml/min/g). Rest LVEF was calculated from end systolic and end diastolic LV volumes on gated images. Cox proportional hazards were used to study the association between MFR (&lt;2 vs ≥2) and incident cardiovascular events stratified by LVEF (&lt;50% vs ≥50%). Results: The study population included 5,523 patients (mean±SD age 67±12 years, 53% male), 16% of LVEF&lt;50% and 47% MFR &lt;2. Rest MBF was similar among patients with normal or reduced LVEF while stress MFR was lower with lower EF. In adjusted analysis, patients with impaired MFR had a higher incident event rate regardless of LVEF (Figure 1). Patients with MFR&lt;2 had a higher risk of incident outcomes in both LVEF ≥50% (HR=2.58, 95% CI:1.93 - 3.46, p&lt;0.001) and LVEF &lt;50% (HR=2.76, 95% CI: 1.62 - 4.70, p&lt;0.001); p-value for interaction= 0.045. Conclusions: Impaired MFR is associated with a higher risk of cardiovascular outcomes and death in patients with high or low LVEF.

Abstract 13332: Assessment of Myocardial Oxygenation Response to Vasoactive Breathing Maneuvers in Patients With Repaired Dextro-Transposition of the Great Arteries an OS-CMR Study

Introduction: Long-term outcomes of patients with repaired Dextro-transposition of the great arteries (D-TGA) by arterial switch operation (ASO) are excellent. However, studies have suggested impaired myocardial blood flow reserve. Oxygen-sensitive cardiac magnetic resonance (OS-CMR) with vasoactive breathing maneuvers (BM) offers a contrast-free tool for evaluating myocardial oxygenation. Hypothesis: Evaluate myocardial oxygenation reserve and microvascular function in repaired D-TGA post-ASO using OS-CMR with BM. Methods: In this single-center study, we analyzed OS-CMR images (basal and mid-left ventricular slices) of 9 D-TGA post-ASO patients (mean age 29 ±6.52yrs, 33.3% females) and 10 healthy participants (mean age 33 ±8.9 yrs, 40% females) who completed the BM. The BM consisted of free breathing, then hyperventilation, causing vasoconstriction, then breath hold, causing vasodilatation. End-systolic OS-CMR signal intensity (SI) was measured at baseline, after hyperventilation (closest to 0 sec of breath hold), and at closest to 30 sec of breath hold. Changes in SI (ΔSI) in % were calculated in response to the different periods and compared using independent samples t-test. Results: In the D-TGA cohort, the coronary response to hyperventilation was abnormal compared to healthy subjects (5.8±19.9% vs -15.1±13.3%, p=0.01). No difference was observed in ΔSI% during breath hold (mean TGA:3.0±10.5% vs mean healthy:5.7±6%, p=0.5). No differences were observed in mid-slices for either period. Conclusions: Our findings suggest patients with D-TGA may have an impaired vasoconstrictor response to a hyperventilation maneuver. Further studies should explore the associated pathophysiology and potential impact on clinical management.

Cytomegalovirus infection is associated with impaired myocardial flow reserve after heart transplantation

BackgroundCardiac allograft vasculopathy (CAV) limits long-term survival after heart transplantation (HT). This study evaluates the relationship between clinically significant CMV infection (CS-CMVi) and CAV using cardiac positron emission tomography (PET). MethodsWe retrospectively evaluated HT patients from 2005-2019 who underwent cardiac PET for CAV evaluation. Multivariable linear and logistic regression models were used to evaluate the association between CS-CMVi and myocardial flow reserve (MFR). Kaplan-Meier and Cox regression analyses were used to assess the relationship between CS-CMV, MFR, and clinical outcomes. ResultsThirty-two (31.1%) of 103 HT patients developed CS-CMVi at a median 9 months after HT. Patients with CS-CMVi had a significantly lower MFR at Year 1 and 3, driven by reduction in stress myocardial blood flow. Patients with CS-CMVi had a faster rate of decline in MFR compared to those without infection (-0.10 vs -0.06 per year, P <0.001). CS-CMVi was an independent predictor of abnormal MFR (<2.0) (OR: 3.8, 95% CI: 1.4-10.7, P = 0.001) and a lower MFR (β = -0.39, 95% CI: -0.63 to -0.16, P = 0.001) at Year 3. In adjusted survival analyses, both abnormal MFR (log-rank P <0.001; HR: 5.7, 95% CI: 4.2-7.2) and CS-CMVi (log-rank P = 0.028; HR: 3.3, 95% CI: 1.8-4.8) were significant predictors of the primary outcome of all-cause mortality, retransplantation, heart failure hospitalization, and acute coronary syndrome. ConclusionCS-CMVi is an independent predictor of reduced MFR following HT. These findings suggest that CMV infection is an important risk factor in the development and progression of CAV.

Interaction of impaired myocardial flow reserve and extent of myocardial ischemia assessed using 13N-ammonia positron emission tomography imaging on adverse cardiovascular outcomes

BackgroundMyocardial flow reserve (MFR) and the extent of myocardial ischemia identify patients at high risk of major adverse cardiovascular events (MACEs). Associations between positron emission tomography (PET)-assessed extent of ischemia, MFR, and MACEs is unclear. MethodOverall, 640 consecutive patients with suspected or known coronary artery disease undergoing 13N-ammonia myocardial perfusion PET were followed-up for MACEs. Patients were categorized into three groups based on myocardial ischemia severity: Group I (n = 335), minimal (myocardial ischemia < 5%); Group II (n = 150), mild (5–10%); and Group III (n = 155), moderate-to-severe (> 10%). ResultsCardiovascular death and MACEs occurred in 17 (3%) and 93 (15%) patients, respectively. Following statistical adjustment for confounding factors, impaired MFR (global MFR < 2.0) was revealed as an independent predictor of MACEs in Groups I (hazard ratio [HR], 2.89; 95% confidence interval [CI], 1.48–5.64; P = 0.002) and II (HR, 3.40; 95% CI 1.37–8.41; P = 0.008) but was not significant in Group III (HR, 1.15; 95% CI 0.59–2.26; P = 0.67), with a significant interaction (P < 0.0001) between the extent of myocardial ischemia and MFR. ConclusionImpaired MFR was significantly associated with increased risk of MACEs in patients with ≤ 10% myocardial ischemia but not with those having > 10% ischemia, allowing a clinically effective risk stratification.

Prognostic value of myocardial flow reserve derived by quantitative SPECT for patients with intermediate coronary stenoses

BackgroundFunctional assessment of myocardial ischemia is critical for patients with intermediate coronary stenosis. As the diagnosis performance of absolute quantification of myocardial blood flow (MBF) and myocardial flow reserve (MFR) by single-photon emission tomography (SPECT) has been proven, its prognostic value in patients with intermediate coronary stenosis remains to be evaluated. MethodsPatients with one or more target lesions of ≥ 50% to ≤ 80% diameter stenoses on invasive coronary angiography were prospectively included in this study. All patients were scheduled for clinically indicated SPECT myocardial perfusion imaging (MPI) within 3 months and agreed to provide informed consent to participate in quantitative SPECT acquisitions to obtain MBF and MFR values. The primary endpoint was defined as a composite of the major adverse cardiac events (MACE): Cardiac death, myocardial infarction, late revascularization and heart failure or unstable angina-related rehospitalization. ResultsOne hundred and nineteen patients (mean age 57 ± 8 years, 62.2% men) were included in the analysis. The average lumen stenosis of patients was 67.0 ± 10.4%. Over a median follow-up duration of 1408 days (interquartile range 1297-1666 days), 18 patients (15.1%) had MACE. Patients with impaired MFR (MFR < 2) had a significantly higher incidence of events than those with preserved MFR (MFR ≥ 2) in Kaplan-Meier survival analysis (Log-rank = 8.105, P = 0.004), while no significant difference was found between patients with normal relative perfusion and those with relative perfusion abnormalities (log-rank = 0.098, P > 0.05). In a multivariate Cox hazards analysis, the SPECT-derived MFR remained an independent predictor of MACE (HR 0.352, 95% CI 0.145-0.854, P = 0.021). ConclusionsIn a cohort of patients with angiographic intermediate coronary lesions, SPECT-derived MFR was an independent predictor of prognosis.

Prognostic value of global myocardial flow reserve in patients with history of coronary artery bypass grafting.

It is not well understood whether positron emission tomography (PET)-derived myocardial flow reserve (MFR) is prognostic among patients with prior coronary artery bypass grafting (CABG). Consecutive patients with a clinical indication for PET were enrolled in the Houston Methodist DeBakey Heart and Vascular Center PET registry and followed prospectively for incident outcomes. The primary outcome was a composite of all-cause death, myocardial infarction (MI)/unplanned revascularization, and heart failure admissions. Cox proportional hazards models were used to study the association between MFR (<2 vs. ≥2) and incident events adjusting for clinical and myocardial perfusion imaging variables. The study population consisted of 836 patients with prior CABG; mean (SD) age 68 (10) years, 53% females, 79% Caucasian, 36% non-Hispanic, and 66% with MFR <2. Over a median (interquartile range [IQR]) follow-up time of 12 (4-24) months, there were 122 incident events (46 HF admissions, 28 all-cause deaths, 23 MI, 22 PCI/3 repeat CABG 90 days after imaging). In adjusted analyses, patients with impaired MFR had a higher risk of the primary outcome [hazard ratio (HR) 2.06; 95% CI 1.23-3.44]. Results were significant for admission for heart failure admissions (HR 2.92; 95% CI 1.11-7.67) but not for all-cause death (HR 2.01, 95% CI 0.85-4.79), or MI/UR (HR 1.93, 95% CI 0.92-4.05). Among patients with a history of CABG, PET-derived global MFR <2 may identify those with a high risk of subsequent cardiovascular events, especially heart failure, independent of cardiovascular risk factors and perfusion data.

Incremental prognostic value of stress phase entropy over standard PET myocardial perfusion imaging variables.

Phase analysis can assess left ventricular dyssynchrony. The independent prognostic value of phase variables over positron emission tomography myocardial perfusion imaging (PET-MPI) variables including myocardial flow reserve (MFR) has not been studied. The aim of this study was to explore the prognostic value of phase variables for predicting mortality over standard PET-MPI variables. Consecutive patients who underwent pharmacological stress-rest 82Rb PET study were enrolled. All PET-MPI variables including phase variables (phase entropy, phase bandwidth, and phase standard deviation) were automatically obtained by QPET software (Cedars-Sinai, Los Angeles, CA). Cox proportional hazard analyses were used to assess associations with all-cause mortality (ACM). In a total of 3963 patients (median age 71years; 57% male), 923 patients (23%) died during a median follow-up of 5years. Annualized mortality rates increased with stress phase entropy, with a 4.6-fold difference between the lowest and highest decile groups of entropy (2.6 vs. 12.0%/year). Abnormal stress phase entropy (optimal cutoff value, 43.8%) stratified ACM risk in patients with normal and impaired MFR (both p < 0.001). Among three phase variables, only stress phase entropy was significantly associated with ACM after the adjustment of standard clinical and PET-MPI variables including MFR and stress-rest change of phase variables, whether modeled as binary variables (adjusted hazard ratio, 1.44 for abnormal entropy [> 43.8%]; 95%CI, 1.18-1.75; p < 0.001) or continuous variables (adjusted hazard ratio, 1.05 per 5% increase; 95%CI, 1.01-1.10; p = 0.030). The addition of stress phase entropy to the standard PET-MPI variables significantly improved the discriminatory power for ACM prediction (p < 0.001), but the other phase variables did not (p > 0.1). Stress phase entropy is independently and incrementally associated with ACM beyond standard PET-MPI variables including MFR. Phase entropy can be obtained automatically and included in clinical reporting of PET-MPI studies to improve patient risk prediction.

Coronary microvascular health in symptomatic patients with prior COVID-19 infection: an updated analysis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with endothelial dysfunction. We aimed to determine the effects of prior coronavirus disease 2019 (COVID-19) on the coronary microvasculature accounting for time from COVID-19, disease severity, SARS-CoV-2 variants, and in subgroups of patients with diabetes and those with no known coronary artery disease. Cases consisted of patients with previous COVID-19 who had clinically indicated positron emission tomography (PET) imaging and were matched 1:3 on clinical and cardiovascular risk factors to controls having no prior infection. Myocardial flow reserve (MFR) was calculated as the ratio of stress to rest myocardial blood flow (MBF) in mL/min/g of the left ventricle. Comparisons between cases and controls were made for the odds and prevalence of impaired MFR (MFR < 2). We included 271 cases matched to 815 controls (mean ± SD age 65 ± 12 years, 52% men). The median (inter-quartile range) number of days between COVID-19 infection and PET imaging was 174 (58-338) days. Patients with prior COVID-19 had a statistically significant higher odds of MFR <2 (adjusted odds ratio 3.1, 95% confidence interval 2.8-4.25 P < 0.001). Results were similar in clinically meaningful subgroups. The proportion of cases with MFR <2 peaked 6-9 months from imaging with a statistically non-significant downtrend afterwards and was comparable across SARS-CoV-2 variants but increased with increasing severity of infection. The prevalence of impaired MFR is similar by duration of time from infection up to 1 year and SARS-CoV-2 variants, but significantly differs by severity of infection.

Association of impaired myocardial flow reserve with risk factors for cardiovascular diseases in patients with nonobstructive coronary artery disease

Aim. To reveal the association between disorders of myocardial blood flow and reserve, according to dynamic single photon emission computed tomography (SPECT), with risk factors for cardiovascular diseases (CVD) in patients with nonobstructive coronary artery disease (CAD).Material and methods. The study included patients with suspected stable nonobstructive (&lt;50%) CAD. Based on the survey data, anamnesis, out- and in-patient medical records, we analyzed main CVD risk factors. All patients underwent dynamic myocardial SPECT and analysis of blood lipid profile in vitro. Depending on myocardial flow reserve (MFR), two groups were formed: 1. With reduced MFR &lt;2,0 (rMFR); 2. With normal MFR ≥2,0 (nMFR).Results. The study included 47 patients divided into 2 following groups: the rMFR group consisted of 24 patients (15 men, age 56,3±9,1 years), the nMFR group — 23 patients (13 men, age 58,4±10,7 years). There was no significant difference in prevalence of CVD risk factors in groups. However, dyslipidemia was detected more often in rMFR patients (p=0,053): 58% vs 30%, respectively. In patients with rMFR, there were significantly higher levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). Correlation analysis revealed significant negative inverse relationships between MFR values with TC (ρ=-0,36, p=0,01) and LDL-C (ρ=-0,38, p=0,009). According to univariate logistic regression, significant predictors of reduced MFR were TC (odds ratio (OR), 2,32; 95% confidence interval (CI), 1,17-4,59; p=0,01) and LDL-C (OR, 2,16; 95% CI, 1,04-4,51; p=0,04). According to a stepwise multivariate logistic regression analysis, only TC was an independent predictor of a decrease in MFR (OR, 2,32; 95% CI, 1,17-4,59; p=0,02).Conclusion. MFR, determined by dynamic SPECT, is associated with TC and LDL-C levels. TC level is an independent predictor of a decrease in MFR.

Incremental prognostic value of positron emission tomography-derived myocardial flow reserve in patients with and without diabetes mellitus.

We aimed to assess the incremental prognostic value of positron emission tomography (PET)-derived myocardial flow reserve (MFR) among patients with diabetes and those without diabetes. Consecutive patients with clinically indicated PET MPI for suspected or established coronary artery disease (CAD) were included. Myocardial blood flow (MBF) in mL/min/g was obtained from dynamic images at rest and stress, while MFR was calculated as the ratio of stress to rest MBF. Patients were followed from the date of PET imaging for the occurrence of the primary outcome (composite of all-cause death, myocardial infarction, and un-planned percutaneous coronary intervention/coronary artery bypass graft occurring more than 90 days after imaging). The final cohort consisted of 6019 patients (63% with diabetes) (mean age 61 ± 11 years, 45% female, 55% obese, 76% hypertensive, and 62% dyslipidaemia). Over half (53%) of the patients had an impaired MFR (<2). During a median follow-up of 22.6 (7.8-42.5) months, 619 patients (10%, 3.8 per 1000 person-years) experienced the primary outcome. Impaired MFR (MFR < 2) was significantly associated with the primary outcome in patients with and without diabetes (diabetes: HR 1.8, 95% CI 1.4-2.3, P < 0.001; no diabetes: 1.4, 95% CI 1.0-2.1, P = 0.046). There was no interaction between diabetes status and MFR (P = 0.234). Results were consistent across subgroups of patients with no CAD and normal perfusion study. PET-derived MFR has a strong independent and incremental prognostic role in patients with diabetes and those without diabetes.

Incremental prognostic value of digital positron emission tomography derived myocardial flow reserve: A prospective cohort study

BackgroundPositron Emission Tomography (PET) Myocardial Perfusion Imaging (MPI) is a robust diagnostic and prognostic test in patients with suspected or known coronary artery disease (CAD). We aimed to assess the incremental prognostic value of myocardial flow reserve (MFR) using the latest generation of digital PET scanners. MethodsConsecutive patients with clinically indicated PET MPI for suspected or known CAD were included. Myocardial blood flow (MBF) in ml/min/g was obtained from dynamic images at rest and peak hyperemia, and the myocardial flow reserve (MFR) was calculated as the ratio of stress to rest MBF. Patients were followed from the date of PET imaging for the occurrence of the primary outcome (composite of all-cause death, myocardial infarction, and Percutaneous Coronary Intervention or Coronary Artery Bypass Graft occurring >90 days after imaging). Nested multivariable Cox regression models were used to assess the incremental prognostic role of MFR over traditional risk factors and PET relative perfusion parameters. ResultsThe final cohort consisted of 3534 patients (mean age 67 ± 12 years, 48% female, 67% Caucasian, 53% obese, 55% hypertension, 32% diabetes, 42% dyslipidemia). During a median follow-up of 8.5 (3.0–15.4) months, 229 patients (6.5%, 6.4 per 1000 person-years) experienced the primary outcome. In nested multivariable Cox models, impaired MFR (MFR < 2) was significantly associated with the primary outcome (HR 2.9, 95% CI 2.0–4.1, p < 0.001) and significantly improved discrimination (Harrell's C 0.77, p = 0.002). ConclusionMFR derived from digital PET scanners has an independent and incremental prognostic role in patients with suspected or known CAD.

Splenic switch-off as a novel marker for adenosine response in nitrogen-13 ammonia PET myocardial perfusion imaging: Cross-validation against CMR using a hybrid PET/MR device

BackgroundNo methodology is available to distinguish truly reduced myocardial flow reserve (MFR) in positron emission tomography myocardial perfusion imaging (PET MPI) from seemingly impaired MFR due to inadequate adenosine response. The adenosine-induced splenic switch-off (SSO) sign has been proposed as a potential marker for adequate adenosine response in cardiac magnetic resonance (CMR). We assessed the feasibility of detecting SSO in nitrogen-13 ammonia PET MPI using SSO in CMR as the standard of reference. Methods and ResultsFifty patients underwent simultaneous CMR and PET MPI on a hybrid PET/MR device with co-injection of a gadolinium-based contrast agent and nitrogen-13 ammonia during rest and adenosine-induced stress. In CMR, SSO was assessed visually (positive vs negative SSO) and quantitatively by calculating the ratio of the peak signal intensity of the spleen during stress over rest (SIR). In PET MPI, the splenic signal activity ratio (SAR) was calculated as the maximal standard uptake value of the spleen during stress over rest. The median SIR was significantly lower in patients with positive versus negative SSO in CMR (0.57 [IQR 0.49 to 0.62] vs 0.89 [IQR 0.76 to 0.98]; P < .001). Similarly, median SAR in PET MPI was significantly lower in patients with positive versus negative SSO (0.40 [IQR 0.32 to 0.45] vs 0.80 [IQR 0.47 to 0.98]; P < .001). ConclusionSimilarly to CMR, SSO can be detected in nitrogen-13 ammonia PET MPI. This might help distinguish adenosine non-responders from patients with truly impaired MFR due to microvascular dysfunction or multivessel coronary artery disease.

Multi-task Deep Learning of Myocardial Blood Flow and Cardiovascular Risk Traits from PET Myocardial Perfusion Imaging

BackgroundAdvanced cardiac imaging with positron emission tomography (PET) is a powerful tool for the evaluation of known or suspected cardiovascular disease. Deep learning (DL) offers the possibility to abstract highly complex patterns to optimize classification and prediction tasks. Methods and ResultsWe utilized DL models with a multi-task learning approach to identify an impaired myocardial flow reserve (MFR <2.0 ml/g/min) as well as to classify cardiovascular risk traits (factors), namely sex, diabetes, arterial hypertension, dyslipidemia and smoking at the individual-patient level from PET myocardial perfusion polar maps using transfer learning. Performance was assessed on a hold-out test set through the area under receiver operating curve (AUC). DL achieved the highest AUC of 0.94 [0.87-0.98] in classifying an impaired MFR in reserve perfusion polar maps. Fine-tuned DL for the classification of cardiovascular risk factors yielded the highest performance in the identification of sex from stress polar maps (AUC = 0.81 [0.73, 0.88]). Identification of smoking achieved an AUC = 0.71 [0.58, 0.85] from the analysis of rest polar maps. The identification of dyslipidemia and arterial hypertension showed poor performance and was not statistically significant. ConclusionMulti-task DL for the evaluation of quantitative PET myocardial perfusion polar maps is able to identify an impaired MFR as well as cardiovascular risk traits such as sex, smoking and possibly diabetes at the individual-patient level.

Coronary vasomotor dysfunction in cancer survivors treated with thoracic irradiation

BackgroundWe sought to test the hypothesis that thoracic radiation therapy (RT) is associated with impaired myocardial flow reserve (MFR), a measure of coronary vasomotor dysfunction. MethodsWe retrospectively studied thirty-five consecutive patients (71% female, mean ± standard deviation (SD) age: 66 ± 11 years) referred clinically for positron emission tomography/computed tomography (PET/CT) myocardial perfusion imaging at a median (interquartile range, IQR) interval of 4.3 (2.1, 9.7) years following RT for a variety of malignancies. Radiation dose-volume histograms were generated for the heart and coronary arteries for each patient. ResultsThe median (IQR) of mean cardiac radiation doses was 12.0 (1.2, 24.2) Gray. There were significant inverse correlations between mean radiation dose and global MFR (MFRGlobal) and MFR in the left anterior descending artery territory (MFRLAD): Pearson’s correlation coefficient = − .37 (P = .03) and − .38 (P = .03), respectively. For every one Gray increase in mean cardiac radiation dose, there was a mean ± standard error decrease of .02 ± .01 in MFRGlobal (P = .04) and MFRLAD (P = .03) after adjustment. ConclusionsIn patients with a history of RT clinically referred for cardiac stress PET, we found an inverse correlation between mean cardiac radiation dose and coronary vasomotor function.

Association Between Impaired Myocardial Flow Reserve on 82Rubidium Positron Emission Tomography Imaging and Adverse Events in Patients With Autoimmune Rheumatic Disease.

Coronary microvascular dysfunction has been described in patients with autoimmune rheumatic disease (ARD). However, it is unknown whether positron emission tomography (PET)-derived myocardial flow reserve (MFR) can predict adverse events in this population. Patients with ARD without coronary artery disease who underwent dynamic rest-stress 82Rubidium PET were retrospectively studied and compared with patients without ARD matched for age, sex, and comorbidities. The association between MFR and a composite end point of mortality or myocardial infarction or heart failure admission was evaluated with time to event and Cox-regression analyses. In 101 patients with ARD (88% female, age: 62±10 years), when compared with matched patients without ARD (n=101), global MFR was significantly reduced (median: 1.68 [interquartile range: 1.34-2.05] versus 1.86 [interquartile range: 1.58-2.28]) and reduced MFR (<1.5) was more frequent (40% versus 22%). MFR did not differ among subtypes of ARDs. In survival analysis, patients with ARD and low MFR (MFR<1.5) had decreased event-free survival for the combined end point, when compared with patients with and without ARD and normal MFR (MFR>1.5) and when compared with patients without ARD and low MFR, after adjustment for the nonlaboratory-based Framingham risk score, rest left ventricular ejection fraction, severe coronary calcification, and the presence of medium/large perfusion defects. In Cox-regression analysis, ARD diagnosis and reduced MFR were both independent predictors of adverse events along with congestive heart failure diagnosis and presence of medium/large stress perfusion defects on PET. Further analysis with inclusion of an interaction term between ARD and impaired MFR revealed no significant interaction effects between ARD and impaired MFR. In our retrospective cohort analysis, patients with ARD had significantly reduced PET MFR compared with age-, sex-, and comorbidity-matched patients without ARD. Reduced PET MFR and ARD diagnosis were both independent predictors of adverse outcomes.

Comparison between cardiac magnetic resonance stress T1 mapping and [15O]H2O positron emission tomography in patients with suspected obstructive coronary artery disease.

To compare cardiac magnetic resonance (CMR) measurement of T1 reactivity (ΔT1) with [15O]H2O positron emission tomography (PET) measurements of quantitative myocardial perfusion. Forty-three patients with suspected obstructed coronary artery disease underwent [15O]H2O PET and CMR at 1.5-T, including rest and adenosine stress T1 mapping (ShMOLLI) and late gadolinium enhancement to rule out presence of scar tissue. ΔT1 was determined for the three main vascular territories and compared with [15O]H2O PET-derived regional stress myocardial blood flow (MBF) and myocardial flow reserve (MFR). ΔT1 showed a significant but poor correlation with stress MBF (R2 = 0.04, P = 0.03) and MFR (R2 = 0.07, P = 0.004). Vascular territories with impaired stress MBF (i.e. ≤2.30 mL/min/g) demonstrated attenuated ΔT1 compared with vascular territories with preserved stress MBF (2.9 ± 2.2% vs. 4.1 ± 2.2%, P = 0.008). In contrast, ΔT1 did not differ between vascular territories with impaired (i.e. <2.50) and preserved MFR (3.2 ± 2.6% vs. 4.0 ± 2.1%, P = 0.25). Receiver operating curve analysis of ΔT1 resulted in an area under the curve of 0.66 [95% confidence interval (CI): 0.57-0.75, P = 0.009] for diagnosing impaired stress MBF and 0.62 (95% CI: 0.53-0.71, P = 0.07) for diagnosing impaired MFR. CMR stress T1 mapping has poor agreement with [15O]H2O PET measurements of absolute myocardial perfusion. Stress T1 and ΔT1 are lower in vascular territories with reduced stress MBF but have poor accuracy for detecting impaired myocardial perfusion.

Coronary microvascular dysfunction, left ventricular remodeling, and clinical outcomes in aortic stenosis

BackgroundWe investigated role of coronary microvascular disease (CMD) in maladaptive LV remodeling and prognosis in patients with aortic sclerosis or stenosis and no overt CAD. MethodsThis was a retrospective cohort study of patients with aortic sclerosis or stenosis, normal myocardial perfusion and LV ejection fraction (EF) > 50% (n = 43) and matched controls without AS (n = 43). PET and echocardiograms were performed within 1 year of each other. Myocardial perfusion and myocardial flow reserve (MFR) were quantified using PET imaging. LV structure and function, including global longitudinal strain (GLS), were quantified by transthoracic echocardiography. ResultsGlobal MFR declined with increasing AS severity (P = 0.04). Probability of impaired MFR increased with severity of adverse LV remodeling (OR 1.88, CI 1.03 to 3.41, P =0.04). Reduced MFR associated with impaired GLS (r = − 0.29, P = 0.002) and associated with reduced MACE-free survival at 7.27 years median follow-up. Adjusted annualized rate of MACE was highest in those with impaired GLS and MFR and lowest in those with normal GLS and MFR (30.99% vs 1.86%, P =0.002). Conclusion and RelevanceIn patients with AS and no overt CAD, impaired MFR associates with adverse LV remodeling and subclinical LV mechanical dysfunction, and is a marker increased clinical risk.

Coronary CT angiography derived features for predicting an abnormal pet myocardial perfusion imaging: a machine learning approach

Abstract Background Computed Tomography Coronary Angiography (CTCA) is an effective non-invasive imaging modality for anatomo-functional assessment of coronary artery disease (CAD). Machine learning (ML) algorithms allow extraction and process of useful information from multidimensional spaces for evaluation of coronary lesions. Purpose To investigate the ability of ML to integrate computational fluid dynamics (CFD) derived parameters with quantitative plaque burden, plaque morphology and anatomical characteristics for predicting impaired myocardial flow reserve by PET myocardial perfusion imaging (MPI). Methods 49 patients (29 male, mean age 65.3±6.3 years) with intermediate pre-test likelihood of CAD who underwent CTCA and PET-MPI were included. PET was considered positive when &amp;gt;1 contiguous segment demonstrated Myocardial flow reserve (MFR) ≤2.5 mL/g/min for 15O-water or ≤2.0 for 13N-ammonia respectively. CDF derived parameters such as a previously validated CT-FFR surrogate, virtual functional assessment index (vFAI), segmental endothelial shear stress (ESS), as well as anatomical and plaque characteristics were assessed. k-nearest neighbor (k-NN), support vector machines (SVM) and feedforward neural networks (FF-NN) were implemented. ML was internally validated using 5-fold cross validation, repeated 100 times. Using sequential forward selection (SFS), the 5 highest rank features based on appearances in each classification scheme were selected and following exhaustive search (ES) the best features combinations were identified. Each classifier's performance was evaluated using an area-under-receiver operating characteristic curve (AUC) analysis. Results 85 coronary segments were analyzed and 28 features derived from CTCA were extracted. The features ranking for every classifier are depicted in Figure 1. k-NN using a combination only of ESS in the proximal (ESSprox) and distal segment achieved an AUC=0.78 (Sens=0.71, Spec=0.77, p&amp;lt;0.05) for predicting a positive PET result. Combining ESSprox with burden fibrofatty tissue and non-calcified plaque burden, SVM achieved an AUC=0.75 (Sens=0.74, Spec=0.67, p&amp;lt;0.05) whilst for FF-NN, the corresponding AUC was 0.79 (Sens=0.76, Spec=0.7, p&amp;lt;0.05) using ESSprox, vFAI and % Fibrofatty volume. Among the best features combinations, ESSprox was the most consistent one achieving an AUC=0.75 (Sens=0.66, Spec=0.73, p&amp;lt;0.05) for k-NN, AUC=0.73 (Sens=0.58, Spec=0.59, p&amp;lt;0.05), for SVM and an AUC=0.73 (Sens=0.63, Spec=0.62, p&amp;lt;0.05) for FF-NN respectively. Conclusion ML analysis is feasible for predicting abnormal MFR by PET using a combination of CFD derived parameters, anatomical and morphological features. ESSprox was present in every combination of best features. As a single characteristic was a moderate predictor of impaired MFR, whilst in combination with plaque characteristics and CFD derived features resulted in improved sensitivity and specificity. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): This research is co-financed by Greece and the European Union (European Social Fund-ESF) through the Operational Programme “Human, Resources Development, Education and Lifelong Learning 2014-2020” in the context of the project “Assessment of coronary atherosclerosis: a new complete, anatomo-functional, morphological and biomechanical approach” and from p-Med GR 5002802