Myocardial Flow Reserve Values Research Articles

Prognostic value of myocardial flow reserve vs corrected myocardial flow reserve in patients without obstructive coronary artery disease

BackgroundMyocardial flow reserve (MFR) by positron emission tomography (PET) is a validated measure of cardiovascular risk. Elevated resting rate pressure product (RPP = heart rate x systolic blood pressure) can cause high resting myocardial blood flow (MBF), resulting in reduced MFR despite normal/near-normal peak stress MBF. When resting MBF is high, it is not known if RPP-corrected MFR (MFRcorrected) helps reclassify CV risk. We aimed to study this question in patients without obstructive coronary artery disease (CAD). MethodsWe retrospectively studied patients referred for rest/stress cardiac PET at our center from 2006 to 2020. Patients with abnormal perfusion (summed stress score >3) or prior coronary artery bypass grafting (CABG) were excluded. MFRcorrected was defined as stress MBF/corrected rest MBF where corrected rest MBF = rest MBF x 10,000/RPP. The primary outcome was major cardiovascular events (MACE): cardiovascular death or myocardial infarction. Associations of MFR and MFRcorrected with MACE were assessed using unadjusted and adjusted Cox regression. Results3276 patients were followed for a median of 7 (IQR 3–12) years. 1685 patients (51%) had MFR <2.0, and of those 366 (22%) had an MFR ≥2.0 after RPP correction. MFR <2.0 was associated with an increased absolute risk of MACE (HR 2.24 [1.79–2.81], P < 0.0001). Among patients with MFR <2.0, the risk of MACE was not statistically different between patients with an MFRcorrected ≥2.0 compared with those with MFRcorrected <2.0 (1.9% vs 2.3% MACE/year, HR 0.84 [0.63–1.13], P = 0.26) even after adjustment for confounders (P = 0.66). ConclusionsIn patients without overt obstructive CAD and MFR< 2.0, there was no significant difference in cardiovascular risk between patients with discordant (≥2.0) and concordant (<2) MFR following RPP correction. This suggests that RPP-corrected MFR may not consistently provide accurate risk stratification in patients with normal perfusion and MFR <2.0. Stress MBF and uncorrected MFR should be reported to more reliably convey cardiovascular risk beyond perfusion results.

Myocardial flow reserve recovery in patients with Takotsubo syndrome: Insights from positron emission tomography

BackgroundCoronary microvascular dysfunction (CMD) has been implicated in the pathogenesis of Takotsubo syndrome (TTS). Positron emission tomography (PET) plays a key role in the assessment of CMD through myocardial flow reserve (MFR). However, there is limited information on the temporal progression of MFR and its relationship to coronary artery disease (CAD) in TTS patients. MethodsThis study evaluated patients with TTS who underwent cardiac catheterization and PET within one year of hospitalization. Patients were categorized into acute (≤10 days), subacute (11–30 days), and chronic (≥31 days) stages based on post-onset time of PET assessment. MFR values and prevalence of abnormal MFR (<2.0) were compared between stages. Temporal MFR changes in patients with obstructive CAD (≥70% stenosis by coronary angiography), non-obstructive CAD, and normal coronaries were compared. ResultsOf the 88 patients studied (mean age 70; 96% female), 52 (59%) were in the acute, 17 (19%) in the subacute, and 19 (22%) in the chronic stage. Median MFR in the acute stage was 2.0 (1.5–2.3), with 58% of patients showing abnormal MFR. A significant time-dependent improvement in MFR was observed (P = 0.002), accompanied by a decreased prevalence of abnormal MFR (P = 0.016). While patients with normal coronaries showed significant MFR improvement over time (P = 0.045), patients with obstructive or non-obstructive CAD demonstrated no improvement across three stages (P = 0.346 and 0.174, respectively). ConclusionPET-derived MFR was impaired in TTS patients during the acute phase, with improvement suggesting potential recovery from CMD over time. The concurrent presence of obstructive CAD might impede this recovery process.

How to assess nonresponsiveness to vasodilator stress

Myocardial perfusion imaging (MPI) is a powerful tool for the functional assessment of ischemia in patients with suspected or known coronary artery disease (CAD). Given that the diagnostic accuracy and prognostic value of MPI and post-test management are highly dependent on achieving an adequate stress vasodilatory response, it is critical to identify those who may not have adequately responded to vasodilator pharmacological stress agents such as adenosine, dipyridamole, and regadenoson. Caffeine, a potent inhibitor of the adenosine receptor, is a compound that can affect vasodilatory hemodynamics, result in false negative studies, and potentially alter management in cases of inaccurate test results. Vasodilator non-responsiveness can be suspected by examining hemodynamics, quantitative positron emission tomography (PET) metrics such as myocardial flow reserve (MFR), and splenic response to stress. Quantitative MFR values of 1–1.2 should raise suspicion for nonresponsiveness in the setting of normal perfusion, along with the absence of a splenic switch off. Newer metrics, such as splenic response ratio, can be used to aid in the identification of potential nonresponders to pharmacologic vasodilators.

Prognostic Role of Myocardial Flow Reserve in Heart Failure With Preserved Ejection Fraction.

Aim To study the role of myocardial blood flow (MBF) and myocardial flow reserve (MFR) in patients with heart failure with preserved ejection fraction (HFpEF) in stratifying the risk of HFpEF progression during 12 months of follow-up.Material and methods The study included 58 patients with non-obstructive coronary artery disease and HFpEF. Concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured using an enzyme-linked immunosorbent assay. MFR and MBF were determined by dynamic single-photon emission computed tomography of the myocardium.Results At 12 months, the patients were divided into two groups: group 1 (n=11) included patients with an unfavorable course of HFpEF, group 2 (n=47) included patients with a favorable course. A multivariate analysis showed that NT-proBNP concentrations (odds ratio (OR), 3.23; 95% confidence interval (CI), 1.76-6.78; p=0.008) and MFR (OR, 8.09; 95% CI, 5.12-19.98; p&lt;0.001) were independent predictors of adverse outcomes. According to ROC analysis, values of MFR ≤1.62 (area under the curve (AUC)=0.827; p&lt;0.001) and NT-proBNP ≥760.5 pg/ml (AUC=0.708; p=0.040) can be considered as markers for HFpEF progression. Furthermore, the combined measurement of NT-proBNP concentration and MFR had a higher prognostic significance (AUC, 0.954; p&lt;0.001).Conclusion Values of NT-proBNP and MFR can be used as noninvasive markers for an unfavorable course of HFpEF, and their combined measurement increases the prognostic significance.

Sex differences in 82Rubidium PET-derived myocardial flow reserve and implications for long-term cardiac outcomes

Abstract Introduction Coronary small vessel disease (CMD), defined by reduced myocardial flow reserve (MFR) in the absence of obstructive coronary artery disease, holds prognostic information on major cardiac events (MACE). We aimed to investigate if the prognostic value of MFR is independent of sex. Method A multicenter registry-based study of 7169 consecutive patients referred to clinically 82Rubidium PET myocardial perfusion imaging. We excluded patients with abnormal perfusion (defects &amp;gt;5% at rest or stress), previous revascularization, cardiomyopathy, or a diagnosis of heart failure. Global MFR≤2 was considered reduced. Patients were followed in registries for major adverse cardiac events (MACE) comprising all-cause mortality and admission for myocardial infarction, stroke, heart failure or unstable angina pectoris. Results A total of 2591 patients were included, 51% women, median age 69 [IQR 60-75] years. Women were older and men had a higher burden of cardiovascular risk factors. Overall, 31% had MFR≤2 (34% women vs 28% men, p&amp;lt;0.001). Mean MFR was lower in women compared with men (2.30 (SD 0.66) vs 2.44 (0.70), respectively) with higher myocardial blood flow both at rest and during stress among women (both p&amp;lt;0.001, Figure 1). In a linear regression model, sex remained associated with MFR after adjustments for age (p&amp;lt;0.001). At 3-year follow-up, MACE was less frequent in women than men (7.0% vs 9.4%, p=0.03). MFR≤2 was associated with MACE with an age-adjusted hazard ratio (HR) of 1.83 (95% CI: 1.20-2.77, p&amp;lt;0.01) in women and 1.75 (1.21-2.54, p&amp;lt;0.01) in men (p for interaction 0.82). The association remained significant after adjustments for left ventricular ejection fraction and charlson comorbidity index with a HR of 1.58 (1.07-2.31, p&amp;lt;0.05) in men and a HR of 1.68 (1.09-2.58, p&amp;lt;0.05) in women (p for interaction 0.69). On a continuous scale, MFR per every 0.1 unit decrease remained significantly associated to MACE (Figure 2). Conclusions Among patients suspected of obstructive CAD, CMD is more prevalent among women than men. The increased hazard of adverse outcomes with CMD did not differ by sex. This study provides new insight into the phenotype and prognosis of patients with CMD.Figure 1:Baseline distribution of MFRFigure 2:HR for MACE

Dynamic perfusion SPECT for functional evaluation in symptomatic patients with myocardial bridging

BackgroundThe aim of this study was to investigate the feasibility and diagnostic value of myocardial flow reserve (MFR) assessed by rest/stress myocardial perfusion imaging with dynamic single-photon emission computed tomography (SPECT) in the functional evaluation of myocardial bridge (MB). MethodsFrom May 2017 to July 2021, patients with angiographically confirmed isolated MB on the left anterior descending artery (LAD) who underwent dynamic SPECT myocardial perfusion imaging were retrospectively included. The assessment of semiquantitative indices of myocardial perfusion (summed stress scores, SSS) and quantitative parameters (MFR) was performed. ResultsA total of 49 patients were enrolled. The mean age of the subjects was 61.0 ± 9.0 years. All of the patients were symptomatic, and 16 cases (32.7%) presented with typical angina. SPECT-derived MFR showed a borderline significantly negative correlation with SSS (r = 0.261, P = .070). There was a trend of higher prevalence of impaired myocardial perfusion defined as MFR < 2 than as SSS ≥ 4 (42.9% vs 26.5%; P = .090). ConclusionOur data support that SPECT MFR may be a useful parameter for the functional assessment of MB. In patients with MB, the use of dynamic SPECT could be a potential method for hemodynamic assessment.

Longitudinal Change and Predictors of Myocardial Flow Reserve by Positron Emission Tomography for the Evaluation of Cardiac Allograft Vasculopathy Following Heart Transplantation

Background: PET myocardial flow reserve (MFR) is a noninvasive method to detect cardiac allograft vasculopathy in heart transplant (HT) recipients. There is limited data on longitudinal change and predictors of MFR following HT. Methods: We conducted a retrospective analysis of HT recipients undergoing PET MPI at an academic center. Multivariable linear and Cox regression models were constructed to identify longitudinal trends, predictors, and prognostic value of MFR after HT. Results: 183 HT recipients underwent 658 PET studies. Average MFR was 2.34 ± 0.70. MFR initially increased in the first three years following HT (+0.12 per year, P = 0.01) before beginning to decline at an annual rate of -0.06 per year (P <0.001). MFR declines preceding acute rejection and improves after treatment. Treatment with mTOR inhibitors (37.2%) slowed the rate of annual MFR decline (P = 0.03). Higher-intensity statin therapy was associated with improved MFR. Longer time post-transplant (p <0.001), hypertension (P <0.001), chronic kidney disease (P < 0.001), diabetes mellitus (P = 0.038), antibody-mediated rejection (P = 0.040), and cytomegalovirus infection (P = 0.034) were associated with reduced MFR. Reduced MFR (HR: 7.6, 95% CI: 4.4-13.4, P <0.001) and PET-defined ischemia (HR: 2.3, 95% CI: 1.4-3.9, P <0.001) was associated with a higher risk of the composite outcome of mortality, retransplantation, heart failure hospitalization, acute coronary syndrome, or revascularization. Conclusion: MFR declines after the third post-transplant year and is prognostic for cardiovascular events. Cardiometabolic risk factor modification and treatment with higher-intensity statin therapy and MTI are associated with a higher MFR.

Dynamic CZT-SPECT: Characterizing the Lower Values of Myocardial Blood Flow and Reserve.

CZT-SPECT myocardial perfusion enables quantification of myocardial blood flow (MBF). Normal values and thresholds have been accurately defined in PET but remain unclear in SPECT. The aim of this study was to report normal MBF and myocardial flow reserve values in very low-risk patients referred for coronary artery disease screening with dynamic SPECT, in comparison with patients experiencing coronary artery disease. Eighty-four patients (31 male) were analyzed. The mean 10 years risk of fatal cardiovascular events score was 2.7% ± 1.4%. The mean global stress MBF and myocardial flow reserve were 1.6 ± 0.6 mL/min/g and 2.7 ± 0.7.

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.

SPECT myocardial blood flow quantitation for the detection of angiographic stenoses with cardiac-dedicated CZT SPECT.

CZT SPECT with the enhanced imaging characteristic facilitates SPECT myocardial blood flow (MBF) quantitation moving toward a clinical utility to uncover myocardial ischemia. The purpose of this study was to investigate the diagnostic performance of stress MBF, myocardial flow reserve (MFR) and myocardial flow capacity (MFC) derived from CZT SPECT in the detection of coronary artery disease (CAD). One-hundred and eighty patients underwent two-day rest/adenosine-stress scans for SPECT MBF quantitation. All dynamic SPECT images were reconstructed and corrected with necessary corrections. The one-tissue two-compartment kinetic model was utilized to fit kinetic parameters (K1, k2 and FBV) by numeric optimization and converted to MBF from K1. Rest MBF, stress MBF and MFR in left ventricle and coronary territories were calculated from flow polar maps. MFC was assessed by extents of moderately and severely abnormal flow statuses using an integrated flow diagram. Per-patient and per-vessel analyses were performed to determine cutoff values for the detection of angiographically obstructive and flow-limited CAD. Using the threshold of ≥50% stenosis, 149 patients (82.78%) were classified to have obstructive lesions in 355 vessels (65.74%). Using the threshold of ≥70% stenosis, 113 patients (62.78%) were classified to have flow-limited lesions in 282 vessels (52.22%). On per-patient analysis, the optimal cutoff values of stress MBF and MFR to detect ≥50% stenosis were (1.44 ml/min/g, 1.96) and (1.34 ml/min/g and 1.75) to detect ≥70% stenosis. The optimal cutoff values for severely and combined moderately severely abnormal MFC extents were (2.3-2.5%, 23.1%) and (7.5%, 29.4%), respectively. The overall sensitivity of MFC (0.84-0.86, 0.86-0.90) to detect ≥50% and ≥70% lesions surpassed those of stress MBF (0.78. 0.78) and MFR (0.80, 0.75) (all p<0.05) with similar specificity (MFC=0.84-0.90, 0.87-0.91; stress MBF=0.87, 0.91; MFR=0.84, 0.89) (all p≥0.05). The non-invasive SPECT MBF quantitation using CZT SPECT is a reliable method to detect angiographically obstructive and flow-limited CAD. Myocardial flow capacity can outperform with higher diagnostic sensitivity than stress MBF or MFR alone.

Prognostic value of myocardial flow reserve measured with CZT cardiac-dedicated SPECT low-dose dynamic myocardial perfusion imaging in patients with INOCA.

Clinical use of dynamic myocardial perfusion imaging (D-MPI) of cadmium-zinc-telluride (CZT) cardiac-dedicated SPECT is growing, showing a higher application value than conventional SPECT. The prognostic value of ischemia in patients with non-obstructive coronary arteries (INOCA) remains an important challenge for investigation. The primary objective of this study was to investigate the prognostic value of myocardial flow reserve (MFR) measured with low-dose D-MPI of CZT cardiac-dedicated SPECT in the assessment of patients with INOCA. Consecutive screening of patients with INOCA and obstructive coronary artery disease (OCAD) who had coronary angiography (CAG) data was performed within three months before or after D-MPI imaging. The patients who met the inclusion criteria were retrospectively analyzed and follow-up by telephone was performed. The enrolled patients were then divided into the INOCA and OCAD groups. INOCA was defined as signs and/or symptoms of myocardial ischemia but with < 50% epicardial stenosis. OCAD was defined as obstructive stenosis (≥ 50% stenosis) of epicardial coronary arteries or their major branches on the CAG. Medical treatments, Seattle Angina Questionnaire (SAQ) scores, and major adverse cardiac events (MACEs) were studied. The Kaplan-Meier survival curve, Log-rank test, and univariable COX regression analysis were used to evaluate the prognosis of patients and associated predictors, with P < 0.05 being considered statistically significant. A total of 303 patients (159 males and 144 females) were enrolled for the final analysis after excluding 24 patients who were lost to follow-up. The mean age of the included cases was 61.94 ± 8.59 years, of which 203 (67.0%) cases were OCAD and 100 (33.0%) cases were INOCA, respectively. The median follow-up was 16 months (14-21 months). Kaplan-Meier survival curves showed that the incidence of MACE was similar in the INOCA and OCAD groups (log-rankP = 0.2645), while those with reduced MFR showed a higher incidence of MACE than those with normal MFR (log-rankP = 0.0019). The subgroup analysis in the OCAD group revealed that 105 patients with reduced MFR had a higher incidence of MACE than those with normal MFR (log-rankP = 0.0226). The subgroup analysis in the INOCA group showed that 37 patients with reduced MFR had a higher incidence of MACE than those with normal MFR in the INOCA group (log-rankP = 0.0186). Univariable Cox regression analysis showed for every 1 unit increase in MFR, the risk of MACE for INOCA was reduced by 66.1% and that for OCAD by 64.2%. For each 1mL·g-1·min-1 increase in LV-sMBF, the risk of MACE was reduced by 72.4% in INOCA patients and 63.6% in OCAD patients. MFR measured with low-dose D-MPI CZT SPECT provides incremental prognostic value in patients with INOCA. Patients with reduced MFR show an increased risk of MACE, increased symptom burdens, and impaired quality of life. INOCA patients with reduced MFR experienced higher rate of MACE than OCAD patients with normal MFR.

Myocardial Flow Assessment After Heart Transplantation Using Dynamic Cadmium-Zinc-Telluride Single-Photon Emission Computed Tomography With 201Tl and 99mTc Tracers and Validated by 13N-NH3 Positron Emission Tomography.

Cardiac allograft vasculopathy (CAV) is an obliterative and diffuse form of vasculopathy and is the most common cause of long-term cardiovascular mortality in heart transplant patients. This study aimed to investigate the diagnostic performance of 99mTc and 201Tl tracers in the assessment of CAV using cadmium-zinc-telluride (CZT) single-photon emission computed tomography (SPECT) for myocardial blood flow (MBF) and myocardial flow reserve (MFR) quantification, which was further validated using 13 N-NH3 positron emission tomography (PET). Thirty-eight patients with prior heart transplantation who underwent CZT SPECT and 13 N-NH3 PET dynamic scans were included in this study. CZT SPECT with 99mTc-sestamibi was used in the first 19 patients and 201Tl-chloride for the remaining patients. To determine the diagnostic accuracy of angiographically defined moderate-to-severe CAV, the analysis included patients who underwent angiographic examinations within 1 year of their second scan. There were no significant differences in the patient characteristics between the 201Tl and 99mTc tracer groups. Both 201Tl and 99mTc CZT SPECT-derived stress MBF and MFR values globally and in 3 coronary territories showed good correlations with 13 N-NH3 PET. The 201Tl and 99mTc cohorts did not differ significantly in the correlation coefficients of CZT SPECT versus PET for MBF and MFR, except for stress MBF (201Tl:0.95 versus 99mTc:0.80, P=0.03). 201Tl and 99mTc CZT SPECT were satisfactory for detecting PET MFR <2.0 (201Tl area under the curve, 0.92 [0.71-0.99], 99mTc area under the curve, 0.87 [0.64-0.97]) and angiographically defined moderate-to-severe CAV, and CZT SPECT results were comparable to that of 13 N-NH3 PET (CZT area under the curve, 0.90 [0.70-0.99], PET area under the curve, 0.86 [0.64-0.97]). This small study suggests that CZT SPECT using 201Tl and 99mTc tracers showed comparable MBF and MFR, and the results correlated well with those of 13 N-NH3 PET. Hence, CZT SPECT with 201Tl or 99mTc tracers can be used to detect moderate-to-severe CAV in patients with prior heart transplantation. However, validation using larger studies is warranted.

Prognostic value of myocardial flow reserve in patients with heart failure with preserved ejection fraction

Aim. To study the prognostic value of myocardial blood flow (MBF) and myocardial flow reserve (MFR) parameters in patients with heart failure with preserved ejection fraction (HFpEF) and non-obstructive coronary artery disease (CAD) in risk stratification of HFpEF progression during a 12-month follow-up.Materials and methods. The study included 58 patients with non-obstructive CAD and HFpEF (LVEF 62 [58; 66]%). Dynamic CZT-SRECT was used to evaluate MFR and MBF at rest (rest-MBF) and stress (stress-MBF). NT-proBNP levels were determined by the enzyme immunoassay. Diastolic dysfunction parameters were measured using 2D transthoracic echocardiography. Left ventricular systolic global longitudinal strain (GLS) was assessed using 2D speckle tracking.Results. After a 12-month follow-up, the patients were retrospectively divided into 2 groups: group 1 (n = 11) included patients with an unfavorable course of HFpEF, group 2 (n = 47) encompassed patients with a favorable course of the disease. In group 1, the level of NT-proBNP was 3.8 times higher than in group 2 (284.5 [183.42; 716.73] and 1,071.4 [272.4; 2,168.1] pg / ml, respectively). MFR values in group 1 were lower by 45.4%(p &lt; 0.001) than in group 2 (1.19 [0.86; 1.55] vs. 2.18 [1.7; 2.55], respectively). In group 1, rest-MBF levels were higher by 23.6% (p = 0.046) and stress-MBF was lower by 28.2% (p = 0.046) than in group 2. The multivariate regression analysis revealed that NT-proBNP levels (odds ratio (OR) 3.23; p = 0.008), GLS (OR 2.27; p = 0.012), and MFR (OR 8.09; p &lt; 0.001) were independent predictors of adverse outcomes in HFpEF. Based on the ROC analysis, MFR levels ≤ 1.62 (AUC = 0.827; p &lt; 0.001), GLS ≤–18 (AUC = 0.756; p = 0.002), and NT-proBNP≥ 760.5 pg / ml (AUC = 0.708; p = 0.040) may be considered as markers of adverse outcomes. However, the combined determination of NT-proBNP and MFR had a greater significance (AUC 0.935; p &lt; 0.001) in risk stratification compared with the monomarker model, while the addition of GLS did not increase the significance of the analysis.Conclusion. Levels of NT-proBNP, GLS, and MFR may be used as non-invasive markers of an adverse course of HFpEF in patients with non-obstructive CAD, while the combined determination of NT-proBNP and MBF increases the prognostic value of the analysis.

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.

The potential of dynamic 99mTc-sestamibi cadmium zinc telluride-single-photon emission computed tomography camera assessing myocardial flow reserve in patients with heart failure with preserved ejection fraction.

Coronary microvascular dysfunction (CMD) is related to the pathophysiology, mortality, and morbidity of heart failure with preserved ejection fraction (HFpEF). A novel single-photon emission computed tomography (SPECT) camera with cadmium zinc telluride (CZT) detectors allows for the quantification of absolute myocardial blood flow and myocardial flow reserve (MFR) in patients with coronary artery disease. However, the potential of CZT-SPECT assessing for CMD has never been evaluated in patients with HFpEF. The clinical records of 127 consecutive patients who underwent dynamic CZT-SPECT were retrospectively reviewed. Rest and stress scanning were started simultaneously with 3 and 9 MBq/kg of 99mTc-sestamibi administration, respectively. Dynamic CZT-SPECT imaging data were analysed using a net-retention model with commercially available software. Transthoracic echocardiography was performed in all patients. The MFR value was significantly lower in the HFpEF group (mean ± SEM = 2.00 ± 0.097) than that in the non-HFpEF group (mean ± SEM = 2.74 ± 0.14, P = 0.0004). A receiver operating characteristic analysis indicated that if a cut-off value of 2.525 was applied, MFR could efficiently distinguish HFpEF from non-HFpEF. Heart failure with preserved ejection fraction had a consistently low MFR, regardless of the diastolic dysfunction score. Heart failure with preserved ejection fraction patients with MFR values lower than 2.075 had a significantly higher incidence of heart failure exacerbation. Myocardial flow reserve assessed by CZT-SPECT was significantly reduced in patients with HFpEF. A lower MFR was associated with a higher hospitalization rate in these patients. Myocardial flow reserve assessed by CZT-SPECT has the potential to predict future adverse events and stratify the severity of disease in patients with HFpEF.

Long-Term Prognostic Value of 82Rb PET/CT-Determined Myocardial Perfusion and Flow Reserve in Cancer Patients.

Myocardial flow reserve (MFR), derived from quantitative measurements of myocardial blood flow during PET imaging, provides prognostic information on patients with coronary artery disease (CAD), but it is not known if this also applies to cancer patients with a competing risk for mortality. Methods: To determine the prognostic value of MFR in patients with cancer, we designed a retrospective cohort study comprising 221 patients with known or suspected CAD (median age, 71 y; range, 41-92 y) enrolled between June 2009 and January 2011. Most patients were referred for perioperative risk assessment. Patients underwent measurement of myocardial blood flow at rest and during pharmacologic stress, using quantitative 82Rb PET imaging. They were divided into early-stage versus advanced-stage cancer groups based on cancer histopathology and clinical state and were further stratified by myocardial perfusion summed stress score, summed difference score, and calculated MFR. Overall survival (OS) was assessed using the Kaplan-Meier estimator, and Cox proportional-hazards regression helped identify independent predictors for OS. Results: During a follow-up of 85.6 mo, 120 deaths occurred. MFR, summed difference score, and cancer stage were significantly associated with OS. In the age-adjusted Cox hazard multivariable analysis, MFR and cancer stage remained independent prognostic factors. MFR combined with cancer stage enhanced OS discrimination. The groups had significantly different outcomes (P < 0.001), with 5-y OS of 88% (MFR ≥ 1.97 and early-stage), 53% (MFR < 1.97 and early-stage), 33% (MFR ≥ 1.97 and advanced-stage), and 13% (MFR < 1.97 and advanced-stage). Conclusion: Independent of cancer stage, MFR derived from quantitative PET was prognostic of OS in our cohort of cancer patients with known or suspected CAD. Combining these 2 parameters enhanced discrimination of OS, suggesting that MFR improves risk stratification and may serve as a treatment target to increase survival in cancer patients.

Prognostic Value of Simultaneous Analysis with Myocardial Flow Reserve and Right Ventricular Strain by Hybrid 13N-Ammonia Positron Emission Tomography/Magnetic Resonance Imaging in Coronary Artery Disease.

Myocardial flow reserve (MFR) derived from 13N-ammonia positron emission tomography (PET) is used to predict adverse cardiac events in patients with coronary artery disease (CAD). Right ventricular global longitudinal strain (RVGLS) measured by magnetic resonance imaging (MRI) is used to evaluate RV function and predict cardiac events. This study aimed to evaluate the prognostic value of MFR and RVGLS measured by hybrid 13N-ammonia PET/MRI in patients with CAD.Sixty-one patients who underwent 13N-ammonia PET/MRI were analyzed. The end points were defined as a composite of all-cause death, myocardial infarction, sustained ventricular arrhythmia, hospitalization due to decompensated heart failure, and revascularization. At a follow-up of 2.8 ± 1.9 years, 21 events had occurred. Kaplan-Meier analysis showed that the event-free rate was significantly lower in the group with MFR < 1.80 than in that with MFR ≥ 1.80 (P < 0.001). Additionally, the event-free rate was significantly lower in the group with RVGLS > -18.22% than in that with RVGLS ≤ -18.22% (P = 0.025). After dividing the patients into 4 groups by the median MFR and the median RVGLS, the event-free rate was lowest in the combined group of MFR < 1.80 and RVGLS > -18.22% than any other groups (P < 0.001). In a Cox proportional hazard analysis, MFR and RVGLS were independent predictors of cardiac adverse events in the patients with CAD.The simultaneous assessment of MFR and RVGLS by 13N-ammonia PET/MRI revealed the feasibility of precise risk stratification for cardiac events in patients with CAD.

Abstract 9916: Prognostic Value of Simultaneous Analysis With Myocardial Flow Reserve and Right Ventricular Strain by Hybrid 13 N-ammonia Positron Emission Tomography/Magnetic Resonance Imaging in Coronary Artery Disease

Introduction: Myocardial flow reserve (MFR) derived from 13 N-ammonia positron emission tomography (PET) is used to predict adverse cardiac events in the patients with coronary artery disease (CAD). Right ventricular (RV) strain measured by magnetic resonance imaging (MRI) is used to evaluate RV function. This study aimed to evaluate the prognostic value of combined MFR and RV strain measured by hybrid 13 N-ammonia PET/MRI in patients with CAD. Methods: Sixty-one patients who underwent 13 N-ammonia PET/MRI were enrolled. MFR was calculated from dynamic acquisition of 13 N-ammonia PET under vasodilator stress with intravenous injection of adenosine. RV global longitudinal strain (GLS) was measured by wall motion tracking techniques in cine-mode MRI. The end points were defined as a composite of all-cause death, myocardial infarction, sustained ventricular arrhythmia, hospitalization due to decompensated heart failure, and revascularization. Results: At a follow-up of 2.8 ± 1.9 years, 21 events occurred. Kaplan-Meier analysis showed that the event-free rate was significantly lower in the group with MFR &lt; 1.80 than that with MFR ≥ 1.80 (P &lt; 0.001, Figure a). Additionally, the event-free rate was significantly lower in the group with RVGLS &gt; –18.22% than that with RVGLS ≤ –18.22% (P = 0.025, Figure b). After dividing the patients into four groups by the median MFR and the median RVGLS, the event-free rate was lowest in the combined group of MFR &lt; 1.80 and RVGLS &gt; -18.22% than any other groups (P &lt; 0.001, Figure c). In the Cox proportional hazard analysis, MFR and RVGLS were independent predictors of cardiac adverse events in the patients with CAD. Conclusion: The simultaneous assessment of MFR and RV strain by 13 N-ammonia PET/MRI revealed the feasibility of precise risk stratification for cardiac events in patients with CAD.

Prognostic value of myocardial flow reserve obtained by 82-rubidium positron emission tomography in long-term follow-up after heart transplantation

BackgroundCardiac allograft vasculopathy (CAV) is a leading cause of death following heart transplantation (HTx) and non-invasive prognostic methods in long-term CAV surveillance are needed. We evaluated the prognostic value of myocardial flow reserve (MFR) obtained by 82-rubidium (82Rb) positron emission tomography (PET). MethodsRecipients undergoing dynamic rest-stress 82Rb PET between April 2013 and June 2017 were retrospectively evaluated in a single-center study. Evaluation by PET included quantitative myocardial blood flow and semiquantitative myocardial perfusion imaging. Patients were grouped by MFR (MFR ≤ 2.0 vs MFR > 2.0) and the primary outcome was all-cause mortality. ResultsA total of 50 patients (68% men, median age 57 [IQR: 43 to 68]) were included. Median time from HTx to PET was 10.0 (6.7 to 16.0) years. In 58% of patients CAV was documented prior to PET. During a median follow-up of 3.6 (2.3 to 4.3) years 12 events occurred. Survival probability by Kaplan–Meier method was significantly higher in the high-MFR group (log-rank P = .02). Revascularization (n = 1), new CAV diagnosis (n = 1), and graft failure (n = 4) were more frequent in low-MFR patients. No retransplantation occurred. ConclusionsMyocardial flow reserve appears to offer prognostic value in selected long-term HTx recipients and holds promise as a non-invasive method for CAV surveillance possibly guiding management strategy.

Integration of quantitative absolute myocardial blood flow estimates from dynamic CZT-SPECT improves the detection of coronary artery disease

BackgroundBalanced ischemia with multi-vessel coronary artery disease (CAD) is difficult to diagnose with semiquantitative single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). Dynamic cardiac SPECT provides quantitative estimations of stenosis severity and ischemic burden by assessing myocardial flow reserve (MFR) and myocardial blood flow (MBF). The aim of this study was to evaluate the incremental value of dynamic SPECT in multi-vessel coronary artery disease (CAD). MethodsPatients with suspected CAD who underwent dynamic ECG-gated dipyridamole MPI and coronary angiography within 6 months were retrospectively reviewed. The performance of summed stress, rest and difference scores (SSS, SRS, SDS), post-stress and resting MBF (MBFs, MBFr) and MFR were compared at both patient level and vessel level. ResultsIn 32 patients with 39 stenotic vessels, 12 had three-vessel disease (38%). Globally increased SSS and impaired MBF values were significantly associated with significant CAD at the patient level, but SDS and MFR were not. Regional increases in SSS and reductions in both MBFs and MBFr were significantly associated with stenotic vessels. The best cutoff value of global MBFs to predict CAD was 3.5 ml·g−1·min−1 (area under the curve, AUC = .84, P = .002). The best cutoff value of regional MBFs to detect significant stenosis was 3.6 ml·g−1·min−1 (AUC = .74, P < .001). However, the best possible cut-off values of MFR were not found. Sex-difference in both global and regional MBFr but MBFs was found, which might result in the non-significance in MFR. ConclusionsThis study validated a clinically available method to quantify MFR using dynamic CZT-SPECT. This method improved the detectability of multi-vessel CAD, and absolute MBFs was superior to MFR and other semiquantitative MPI parameters.