Ines Valenta

Diagnostic value of PET-measured longitudinal flow gradient for the identification of coronary artery disease.

OBJECTIVESnThe purpose of this study was to evaluate the diagnostic value of a positron emission tomography (PET)/computed tomography (CT)-determined longitudinal decrease in myocardial blood flow (MBF) gradient during hyperemia and myocardial flow reserve (MFR) for the identification of epicardial stenosis ≥50%.nnnBACKGROUNDnAlthough PET-determined reductions in MFR are increasingly applied to identify epicardial lesions in coronary artery disease (CAD), it may be seen as a suboptimal approach due to the nonspecific origin of decreases in MFR.nnnMETHODSnIn 24 patients with suspected or known CAD, MBF was measured with (13)N-ammonia and PET/CT in ml/g/min at rest, during dipyridamole stimulation, and the corresponding MFR was calculated. MBF was also determined in the mid and mid-distal myocardium of the left ventricle (LV). A decrease in MBF from mid to mid-distal LV myocardium was defined as longitudinal MBF gradient. MBF parameters were determined in the myocardial region with stress-induced perfusion defect and with stenosis ≥50% (territory 1), without defect but with stenosis ≥50% (territory 2), or without stenosis ≥50% (territory 3).nnnRESULTSnIn territories 1 and 2 with focal stenosis ≥50%, the severity of epicardial artery stenosis correlated with the Δlongitudinal MBF gradient (stress-rest) (rxa0= 0.52; p < 0.0001), while this association was less pronounced for corresponding MFR (rxa0=xa0-0.40; p < 0.003). On a vessel-based analysis, the sensitivity and specificity of the Δlongitudinal MBF gradient in the identification of epicardial lesions was higher than those for MFR (88% vs. 71%, p ≤ 0.044; and 81% vs. 63%, pxa0= 0.134, respectively). Combining both parameters resulted in an optimal sensitivity of 100% and intermediate specificity of 75%. The diagnostic accuracy was highest for the combined analysis than for the Δlongitudinal MBF gradient or MFR alone (94% vs. 86%, p ≤ 0.003; and 94% vs. 70%, p ≤ 0.0002).nnnCONCLUSIONSnThe combined evaluation of a Δlongitudinal MBF gradient and MFR may evolve as a new promising analytic approach to further optimize the identification of CAD lesions.

Impact of Obesity and Bariatric Surgery on Metabolism and Coronary Circulatory Function

Increases in intra-abdominal visceral adipose tissue have been widely appreciated as a risk factor for metabolic disorders such as dyslipidemia, hypertension, insulin resistance, and type 2 diabetes, whereas this is not the case for peripheral or subcutaneous obesity. While the underlying mechanisms that contribute to these differences in adipose tissue activity remain uncertain, increases in visceral fat commonly induce metabolic dysregulation, in part because of increased venous effluent of fatty acids and/or adipokines/cytokines to the liver. Increased body weight, paralleled by an increase in plasma markers of the insulin-resistance syndrome and chronic inflammation, is independently associated with coronary circulatory dysfunction. Recent data suggest that plasma proteins originating from the adipose tissue, such as endocannabinoids (EC), leptin, and adiponectin (termed adipocytes) play a central role in the regulation and control of coronary circulatory function in obesity. Positron emission tomography (PET) in concert with tracer kinetic modeling is a well established technique for quantifying regional myocardial blood flow at rest and in response to various forms of vasomotor stress. Myocardial flow reserve assessed by PET provides a noninvasive surrogate of coronary circulatory function. PET also enables the monitoring and characterization of coronary circulatory function in response to gastric bypass-induced weight loss in initially morbidly obese individuals, to medication and/or behavioral interventions related to weight, diet, and physical activity. Whether the observed improvement in coronary circulatory dysfunction via weight loss may translate to diminution in cardiovascular events awaits clinical confirmation.

PET-measured longitudinal flow gradient correlates with invasive fractional flow reserve in CAD patients.

AimsnWe aimed to evaluate whether a PET-determined longitudinal decrease in myocardial blood flow (MBF) or gradient, assumed as a more specific flow parameter for epicardial resistance, correlates with invasively measured fractional flow reserve (FFR) in coronary artery disease (CAD) patients.nnnMethods and ResultsnIn 29 patients with suspected or known CAD, myocardial perfusion and MBF in mL/g/min was determined with 13N-ammonia PET/CT during regadenoson stimulation and at rest, and corresponding myocardial flow reserve (MFR = MBF stress/MBF rest) was calculated. MBF parameters were assessed in the myocardial region with stress-related perfusion defect and with stenosis ≥50% (Region 1), without defect but with stenosis ≥50% (Region 2), or without stenosis ≥50% (Region 3). Hyperaemic MBFs were significantly lower in the mid-distal than in the mid-left ventricular myocardium in Regions 1-3 [median and IQ range: 1.57 (1.24, 1.84) vs. 1.87 (1.61, 2.00), and 1.23 (1.11, 1.86) vs. 1.89 (1.80, 1.97), and 1.78 (1.48, 2.00) vs. 1.94 (1.84, 2.05) mL/g/min, P < 0.0001]. Resulting longitudinal MBF gradient during hyperaemic flows was more pronounced in Region 2 than in Regions 1 and 3, respectively [-0.46 (-0.70, -0.10) vs. -0.17 (-0.29, -0.11) and -0.15 (-0.25, -0.09) mL/g/min, respectively, P < 0.01]. There was a significant correlation between the hyperaemic longitudinal MBF gradient and FFR (r = 0.95; P < 0.0001), while this association was less pronounced for corresponding MFR (r = 0.50; P = 0.006).nnnConclusionnThe observed close correlation between a longitudinal MBF gradient during hyperaemic flows and invasively measured FFR suggests the longitudinal flow gradient as an emerging non-invasive index of flow-limiting CAD.

Effect of Diffuse Subendocardial Hypoperfusion on Left Ventricular Cavity Size by 13N-Ammonia Perfusion PET in Patients With Hypertrophic Cardiomyopathy

Vasodilator-induced transient left ventricular (LV) cavity dilation by positron emission tomography (PET) is common in patients with hypertrophic cardiomyopathy (HC). Because most patients with PET-LV cavity dilation lack obstructive epicardial coronary artery disease, we hypothesized that vasodilator-induced subendocardial hypoperfusion resulting from microvascular dysfunction underlies this result. To test this hypothesis, we quantified myocardial blood flow (MBF) (subepicardial, subendocardial, and global MBF) and left ventricular ejection fraction (LVEF) in 104 patients with HC without significant coronary artery disease, using 13NH3-PET. Patients with HC were divided into 2 groups, based on the presence/absence of LV cavity dilation (LVvolumestress/LVvolumerest >1.13). Transient PET-LV cavity dilation was evident in 52% of patients with HC. LV mass, stress left ventricular outflow tract gradient, mitral E/E, late gadolinium enhancement, and prevalence of ischemic ST-T changes after vasodilator were significantly higher in patients with HC with LV cavity dilation. Baseline LVEF was similar in the 2 groups, but LV cavity dilation+ patients had lower stress-LVEF (43 ± 11 vs 53 ± 10; p <0.001), lower stress-MBF in the subendocardial region (1.6 ± 0.7 vs 2.3 ± 1.0xa0ml/min/g; p <0.001), and greater regional perfusion abnormalities (summed difference score: 7.0 ± 6.1 vs 3.9 ± 4.3; pxa0= 0.004). The transmural perfusion gradient, an indicator of subendocardial perfusion, was similar at rest in the 2 groups. Notably, LV cavity dilation+ patients had lower stress-transmural perfusion gradients (0.85 ± 0.22, LV cavity dilation+ vs 1.09 ± 0.39, LV cavity dilation-; pxa0<0.001), indicating vasodilator-induced subendocardial hypoperfusion. The stress-transmural perfusion gradient, global myocardial flow reserve, and stress-LVEF were associated with LV cavity dilation. In conclusion, diffuse subendocardial hypoperfusion and myocardial ischemia resulting from microvascular dysfunction contribute to development of transient LV cavity dilation in HC.

Stress Myocardial Blood Flow Heterogeneity Is a Positron Emission Tomography Biomarker of Ventricular Arrhythmias in Patients With Hypertrophic Cardiomyopathy

Patients with hypertrophic cardiomyopathy (HC) are at increased risk of sudden cardiac death. Abnormalities in myocardial blood flow (MBF) detected by positron emission tomography (PET) are common in HC, but a PET marker that identifies patients at risk of sudden cardiac death is lacking. We hypothesized that disparities in regional myocardial perfusion detected by PET would identify patients with HC at risk of ventricular arrhythmias. To test this hypothesis, we quantified global and regional MBFs by 13NH3-PET at rest and at stress, and developed a heterogeneity index to assess MBF heterogeneity in 133 symptomatic patients with HC. The MBF heterogeneity index was computed by dividing the highest by the lowest regional MBF value, at rest and after vasodilator stress, in each patient. High stress MBF heterogeneity was defined as an index of ≧1.85. Patients with HC were stratified by the presence or the absence of ventricular arrhythmias, defined as sustained ventricular tachycardia (VT) and/or nonsustained VT, during follow-up. We found that global and regional MBFs at rest and stress were similar in patients with HC with or without ventricular arrhythmias. Variability in regional stress MBF was observed in both groups, but the stress MBF heterogeneity index was significantly higher in patients with HC who developed ventricular arrhythmias (1.82u2009±u20090.77 vs 1.49u2009±u20090.25, pu2009<0.001). A stress MBF heterogeneity index of ≧1.85 was an independent predictor of both sustained VT (hazard ratio 16.1, 95% confidence interval 3.2 to 80.3) and all-VT (sustained-VTu2009+u2009nonsustained VT: hazard ratio 3.7, 95% confidence interval 1.4 to 9.7). High heterogeneity of stress MBF, reflected by an MBF heterogeneity index of ≥1.85, is a PET biomarker for ventricular arrhythmias in symptomatic patients with HC.

Potential Role of Cardiovascular Imaging in Improving Cardiovascular Outcome in Coronary Artery Disease.

BACKGROUNDnThere is increasing interest in cardiovascular imaging modalities in the detection of subclinical and clinically-manifested coronary artery disease (CAD) to improve cardiovascular outcome in these patients.nnnMETHODSnSPECT/CT and PET/CT can be applied for the assessment of myocardial perfusion and myocardial blood flow (MBF) quantification in CAD detection and characterization, while CT is predominantly used to identify coronary plaque burden and epicardial narrowing. In addition, PET/CT plays an increasing role in the detection of the vulnerable plaque in the epicardial artery.nnnRESULTSnImaging of myocardial perfusion with SPECT, SPECT/CT and PET/CT is a mainstay in clinical practice for the identification of flow-limiting epicardial lesions and risk stratification of patients with suspected or known CAD. In this direction, the concurrent ability of PET/CT to determine regional myocardial blood flow (MBF) in ml/g/min at rest and during pharmacologically- induced hyperemic flows allows the calculation of the myocardial flow reserve (MFR) that may unravel reductions in coronary vasodilator capacity, as functional precursor of the CAD process, monitor its response to preventive medical intervention, yield important prognostic information in subclinical - and clinically-manifested CAD, and contributes to identify the flow-limiting effect of single lesions in multivessel CAD. Adding noncontrast computed-tomography (CT) measurements of coronary artery calcifications has further improved the reclassification of cardiovascular risk in asymptomatic individuals with intermediate probability of the presence of CAD. With contrast CT, the non-invasive visualization of coronary vessels, CAD-related plaque burden and stenosis has become feasible. Yet, a definite identification of the vulnerable plaque is still a matter of ongoing research. PET/CT in conjunction with various positron-emitting radiotracer yields promise in the detection of the vulnerable plaque, that, however, needs further clinical evaluation in CAD patients.nnnCONCLUSIONnMultimodality imaging in cardiovascular disease is likely to further advances and refine the identification and characterization of cardiovascular pathology in the near future.

Correction to: Comparison of two software systems for quantification of myocardial blood flow in patients with hypertrophic cardiomyopathy

The following information is missing from the Funding footnote on the first page of the published article: “This study was partly funded by NIH RO1 HL092985.” The last/corresponding author is incorrectly listed on the first page of the published article: The correct name is Abraham MR.

Comparison of two software systems for quantification of myocardial blood flow in patients with hypertrophic cardiomyopathy

BackgorundQuantification of myocardial blood flow (MBF) by positron emission tomography (PET) is important for investigation of angina in hypertrophic cardiomyopathy (HCM). Several software programs exist for MBF quantification, but they have been mostly evaluated in patients (with normal cardiac geometry), referred for evaluation of coronary artery disease (CAD). Software performance has not been evaluated in HCM patients who frequently have hyperdynamic LV function, LV outflow tract (LVOT) obstruction, small LV cavity size, and variation in the degree/location of LV hypertrophy.AimWe compared results of MBF obtained using PMod, which permits manual segmentation, to those obtained by FDA-approved QPET software which has an automated segmentation algorithm.Methods13N-ammonia PET perfusion data were acquired in list mode at rest and during pharmacologic vasodilation, in 76 HCM patients and 10 non-HCM patients referred for evaluation of CAD (CAD group.) Data were resampled to create static, ECG-gated and 36-frame-dynamic images. Myocardial flow reserve (MFR) and MBF (in ml/min/g) were calculated using QPET and PMod softwares.ResultsAll HCM patients had asymmetric septal hypertrophy, and 50% had evidence of LVOT obstruction, whereas non-HCM patients (CAD group) had normal wall thickness and ejection fraction. PMod yielded significantly higher values for global and regional stress-MBF and MFR than for QPET in HCM. Reasonably fair correlation was observed for global rest-MBF, stress-MBF, and MFR using these two softwares (rest-MBF: rxa0=xa00.78; stress-MBF: rxa0=xa00.66.; MFR: rxa0=xa00.7) in HCM patients. Agreement between global MBF and MFR values improved when HCM patients with high spillover fractions (>xa00.65) were excluded from the analysis (rest-MBF: rxa0=xa00.84; stress-MBF: rxa0=xa00.72; MFR: rxa0=xa00.8.) Regionally, the highest agreement between PMod and QPET was observed in the LAD territory (rest-MBF: rxa0=xa00.82, Stress-MBF: rxa0=xa00.68) where spillover fraction was the lowest. Unlike HCM patients, the non-HCM patients (CAD group) demonstrated excellent agreement in MBF/MFR values, obtained by the two softwares, when patients with high spillover fractions were excluded (rest-MBF: rxa0=xa00.95; stress-MBF: rxa0=xa00.92; MFR: rxa0=xa00.95).ConclusionsAnatomic characteristics specific to HCM hearts contribute to lower correlations between MBF/MFR values obtained by PMod and QPET, compared with non-HCM patients. These differences indicate that PMod and QPET cannot be used interchangeably for MBF/MFR analyses in HCM patients.

Concepts of PET, SPECT, and MRI in the Assessment of Myocardial Viability Leading to PET/MRI Application

The prevalence of heart failure is continuously rising in view of the increasingly elderly population and improved survival of acute coronary syndrome patients. Although heart failure can be related to various causes such as idiopathic cardiomyopathy, valvular disease, hypertensive, and diabetic heart disease, ischemic heart disease is the predominant cause of the majority of patients with heart failure symptoms. Exercise-induced and repetitive myocardial ischemia commonly induces cumulative myocardial stunning-hibernation that over time may manifest clinically as left ventricular dysfunction with heart failure symptoms. Stunning-hibernation myocardium may completely or partially restore its function in a substantial number of patients, in whom coronary flow is restored by interventional or surgical revascularization. The identification of stunning-hibernation myocardium, or ischemic compromised viable but dysfunctional myocardial regions, with imaging is critical for the clinical assessment of ischemic heart failure patients. There is a variety of cardiac imaging modalities to identify stunning-hibernation myocardium. This chapter emphasizes on the concepts of PET, SPECT, and MRI in the assessment of myocardial viability leading to the advantages of PET/MRI application. In addition, clinical determinants such as timely revascularization of ischemic, jeopardized but viable myocardium, effects of advanced stages of myocardial remodeling, ischemic conditioning, and the extent of left-ventricular dilation will be given considerations.