Adenosine-induced Hyperemia Research Articles

Coronary microvascular ischemia in hypertrophic cardiomyopathy - a pixel-wise quantitative cardiovascular magnetic resonance perfusion study.

BackgroundMicrovascular dysfunction in HCM has been associated with adverse clinical outcomes. Advances in quantitative cardiovascular magnetic resonance (CMR) perfusion imaging now allow myocardial blood flow to be quantified at the pixel level. We applied these techniques to investigate the spectrum of microvascular dysfunction in hypertrophic cardiomyopathy (HCM) and to explore its relationship with fibrosis and wall thickness.MethodsCMR perfusion imaging was undertaken during adenosine-induced hyperemia and again at rest in 35 patients together with late gadolinium enhancement (LGE) imaging. Myocardial blood flow (MBF) was quantified on a pixel-by-pixel basis from CMR perfusion images using a Fermi-constrained deconvolution algorithm. Regions-of-interest (ROI) in hypoperfused and hyperemic myocardium were identified from the MBF pixel maps. The myocardium was also divided into 16 AHA segments.ResultsResting MBF was significantly higher in the endocardium than in the epicardium (mean ± SD: 1.25 ± 0.35 ml/g/min versus 1.20 ± 0.35 ml/g/min, P < 0.001), a pattern that reversed with stress (2.00 ± 0.76 ml/g/min versus 2.36 ± 0.83 ml/g/min, P < 0.001). ROI analysis revealed 11 (31%) patients with stress MBF lower than resting values (1.05 ± 0.39 ml/g/min versus 1.22 ± 0.36 ml/g/min, P = 0.021). There was a significant negative association between hyperemic MBF and wall thickness (β = −0.047 ml/g/min per mm, 95% CI: −0.057 to −0.038, P < 0.001) and a significantly lower probability of fibrosis in a segment with increasing hyperemic MBF (odds ratio per ml/g/min: 0.086, 95% CI: 0.078 to 0.095, P = 0.003).ConclusionsPixel-wise quantitative CMR perfusion imaging identifies a subgroup of patients with HCM that have localised severe microvascular dysfunction which may give rise to myocardial ischemia.

Normal range and regional heterogeneity of myocardial perfusion in healthy human myocardium: assessment on dynamic perfusion CT using 128-slice dual-source CT

Information about myocardial perfusion in healthy hearts is essential for evaluating patients with ischemic heart disease. The purpose of this study was to determine the range and regional variability of myocardial perfusion in normal volunteers on dynamic perfusion computed tomography (CT). Myocardial perfusion was assessed in 19 healthy volunteers (age 33-60 years; 11 men) at rest and during adenosine-induced hyperemia using a 128-slice dual-source CT scanner. Data were quantified as cc/cc/min for the transmural myocardium based on a 17-segment American Heart Association model. Mean myocardial blood flows (MBF) were 1.73 ± 0.33 cc/cc/min during adenosine-induced hyperemia, 0.83 ± 0.21 cc/cc/min at rest, and perfusion reserve was 2.20 ± 0.53. Regional variability was 17 ± 5% for hyperemic perfusion, 18 ± 7% for resting, and 21 ± 6 % for perfusion reserve. Although statistically insignificant, perfusion in the septum was lower at rest and during hyperemia than in other regions. Women tended to have lower perfusion during hyperemia (1.65 ± 0.40 vs. 1.79 ± 0.28 cc/cc/min, P = 0.40), and higher perfusion at rest than men (0.91 ± 0.27 vs. 0.77 ± 0.15 cc/cc/min, P = 0.23), resulting in lower perfusion reserve (1.86 ± 0.31 vs. 2.45 ± 0.53, P = 0.11). This small cohort of healthy volunteers study reveals normal myocardial perfusion parameter on dynamic perfusion CT as follows: mean MBF is 1.73 ± 0.33 cc/cc/min during hyperemia, 0.83 ± 0.21 cc/cc/min at rest, and perfusion reserve is 2.20 ± 0.53. And the study also demonstrates considerable regional heterogeneity of the myocardial perfusion.

Increased hyperaemic coronary microvascular resistance adds to the presence of myocardial ischaemia.

It has been argued that hyperaemic microvascular resistance (HMR), defined as the ratio of mean distal coronary pressure to flow velocity, is overestimated in the presence of a coronary stenosis compared to actual microvascular resistance (MR), due to neglecting collateral flow. We aimed to test the hypothesis that HMR allows accurate identification of microvascular functional abnormalities by evaluating the association between high or low HMR and the presence of myocardial ischaemia on non-invasive stress testing. Myocardial perfusion scintigraphy was performed in 228 patients, with 299 lesions to identify reversible myocardial ischaemia. Intracoronary distal pressure and flow velocity were assessed during adenosine-induced hyperaemia (20-40 µg, intracoronary) to determine hyperaemic stenosis resistance (HSR) and HMR. HMR >1.9 mmHg/cm/s was defined as high. The diagnostic odds ratio (OR) for myocardial ischaemia for lesions associated with high compared to low HMR was 2.6 (95% confidence interval [CI]: 1.5-4.4; p<0.001) overall, 3.3 (95% CI: 1.2-9.0; p=0.02) for lesions with HSR >0.8 mmHg/cm/s, and 1.3 (95% CI: 0.6-2.9; p=0.52) for lesions with HSR ≤0.8 mmHg/cm/s. The increased risk of myocardial ischaemia in the presence of high HMR, uncorrected for collateral flow, demonstrates that HMR is reflective of an increase in actual MR, identifying pertinent pathophysiological alterations in the microvasculature.

Impact of Accuracy of Fractional Flow Reserve to Reduction of Microvascular Resistance After Intracoronary Adenosine in Patients With Angina Pectoris or Non–ST-Segment Elevation Myocardial Infarction

Our study aimed to elucidate mechanisms underlying discordance between fractional flow reserve (FFR) and hyperemic stenosis resistance (hSR) in some patient subsets. To do this, we enrolled 30 consecutive patients with stable angina or non-ST elevation myocardial infarction (non-STEMI) and with a nonculprit intermediate coronary lesion (40% to 70%) by coronary angiography. We measured aortic pressure, flow velocity, and pressure distal to lesion simultaneously at basal level and during adenosine-induced (fixed intracoronary dose of 120 μg) hyperemia using a dual-sensor-equipped guidewire. Microvascular resistance (MR; pressure distal to lesion/flow velocity, mm Hg/cm/s) and variation (Δ) in MR levels were calculated both at baseline and after hyperemia, whereas FFR (cutoff <0.80) and hSR [(aortic pressure- pressure distal to lesion)/flow velocity, cutoff >0.80 mm Hg/cm/s] were assessed after intracoronary adenosine. Twenty-three patients (76.7%) showed concordance and 7 patients (23.3%) showed discordance between FFR and hSR (all cases with FFR >0.80 and hSR >0.80). Discordant patients presented more frequently with non-STEMI (85.7% vs 39.1%, p= 0.04), significantly higher C-reactive protein serum levels (median [interquartile range] 5.9 [5.1 to 6.8] vs 4.9 [3.7 to 6.2] mg/L, p= 0.007), and lower ΔMR (p= 0.03) values compared with concordant patients. In conclusion, patients with non-STEMI and those with increased C-reactive protein levels show a lower reduction in MR after intracoronary adenosine-induced hyperemia, leading to FFR underestimation.

Wave speed in human coronary arteries is not influenced by microvascular vasodilation: implications for wave intensity analysis

Wave intensity analysis and wave separation are powerful tools for interrogating coronary, myocardial and microvascular physiology. Wave speed is integral to these calculations and is usually estimated by the single-point technique (SPc), a feasible but as yet unvalidated approach in coronary vessels. We aimed to directly measure wave speed in human coronary arteries and assess the impact of adenosine and nitrate administration. In 14 patients, the transit time Δt between two pressure signals was measured in angiographically normal coronary arteries using a microcatheter equipped with two high-fidelity pressure sensors located Δs=5cm apart. Simultaneously, intracoronary pressure and flow velocity were measured with a dual-sensor wire to derive SPc. Actual wave speed was calculated as DNc=Δs/Δt. Hemodynamic signals were recorded at baseline and during adenosine-induced hyperemia, before and after nitroglycerin administration. The energy of separated wave intensity components was assessed using SPc and DNc. At baseline, DNc equaled SPc (15.9±1.8 vs. 16.6±1.5m/s). Adenosine-induced hyperemia lowered SPc by 40% (p<0.005), while DNc remained unchanged, leading to marked differences in respective separated wave energies. Nitroglycerin did not affect DNc, whereas SPc transiently fell to 12.0±1.2m/s (p<0.02). Human coronary wave speed is reliably estimated by SPc under resting conditions but not during adenosine-induced vasodilation. Since coronary wave speed is unaffected by microvascular dilation, the SPc estimate at rest can serve as surrogate for separating wave intensity signals obtained during hyperemia, thus greatly extending the scope of WIA to study coronary physiology in humans.

Myocardial blood flow under general anaesthesia with sevoflurane in type 2 diabetic patients: a pilot study

BackgroundIn type 2 diabetic patients, cardiac events in the perioperative period may be associated with diminished myocardial vasomotor function and endothelial dysfunction. The influence of sevoflurane anaesthesia on myocardial endothelial dysfunction in type 2 diabetic mellitus is investigated in this pilot study.MethodsSix males with type 2 diabetes mellitus and eight healthy controls were included. Using myocardial contrast echocardiography, myocardial blood flow (MBF) was measured at rest, during adenosine-induced hyperaemia (endothelium-independent vasodilation) and after sympathetic stimulation by the cold pressor test (endothelium-dependent vasodilation). Measurements were performed before and after induction of sevoflurane anaesthesia.ResultsSevoflurane anaesthesia decreased resting MBF in diabetics but not in controls (P = 0.03), while baseline MBF did not differ between diabetics and controls. Without anaesthesia, adenosine-induced hyperaemia increased MBF in both groups compared to resting values. Adenosine combined with sevoflurane resulted in a lower hyperaemic MBF in both groups compared to no anaesthesia. Differences in MBF in response to adenosine before and after sevoflurane administration were larger in diabetic patients, however not statistically significant in this pilot group (P = 0.08). Myocardial blood flow parameters after the cold pressor test were not different between groups.ConclusionThese pilot data in type 2 diabetic patients show that sevoflurane anaesthesia decreases resting myocardial blood flow compared to healthy controls. Further, we observed a trend towards a lower endothelium-independent vasodilation capacity in diabetic patients under sevoflurane anaesthesia. Endothelium-dependent vasodilation was not affected by sevoflurane in diabetic patients. These data provide preliminary insight into myocardial responses in type 2 diabetic patients under general anaesthesia.Trial registrationhttp://www.clinicialtrials.gov, NCT00866801

Intracoronary versus Intravenous Adenosine-Induced Maximal Coronary Hyperemia for Fractional Flow Reserve Measurements

BACKGROUNDMaximal hyperemia is the critical prerequisite for fractional flow reserve (FFR) assessment. Despite intravenous (IV) adenosine currently being the recommended approach, intracoronary (IC) administration of adenosine constitutes a valuable alternative in everyday practice. However, it is surprisingly unclear which IC strategy allows the achievement of FFR values that are comparable to IV adenosine.OBJECTIVESThis study sought to compare increasing doses of IC adenosine versus IV adenosine for FFR.METHODS30 intermediate coronary stenoses undergoing FFR measurement were prospectively and consecutively enrolled. Hyperemia was sequentially induced by bolus of IC adenosine (ADN; 150 μg) followed by IV adenosine (IVADN) infusion over 3 minutes at dose of (140 μg/kg/min). FFR values, symptoms, and development of atrioventricular block were recorded.RESULTS150 μg doses of IC adenosine were well tolerated and associated with fewer symptoms than IV adenosine. Intracoronary adenosine doses induced a significant decrease of FFR compared with baseline levels (P < 0.01). Among the 6 patients with FFR values less than 0.80 identified by IVADN, 4 were correctly identified also by 150 μg bolus IC adenosine. Larger randomized studies with cross-over design are necessary to verify the results.CONCLUSIONSThis small pilot study suggests that IC adenosine might be an alternative to IV adenosine. Larger randomized studies with a cross-over design are necessary.

Effect of Type 2 Diabetes Mellitus on Epicardial Adipose Tissue Volume and Coronary Vasomotor Function

Patients with coronary artery disease and/or type 2 diabetes mellitus (DM) generally exhibit more epicardial adipose tissue (EAT) than healthy controls. Recently, it has been proposed that EAT affects vascular function and structure by secreting proinflammatory and vasoactive substances, thereby potentially contributing to the development of cardiovascular disease. In the present study, the interrelation of EAT, coronary vasomotor function, and coronary artery calcium was investigated in patients with and without DM, who were evaluated for coronary artery disease. Myocardial blood flow (MBF) was assessed at rest and during adenosine-induced hyperemia using [(15)O]-water positron emission tomography combined with computed tomography to quantify coronary artery calcium and EAT in 199 patients (46 with DM). In this cohort (mean age 58 ± 10 years), the patients with DM had a greater body mass index, heart rate, and systolic blood pressure at rest (all p <0.05). Coronary artery calcium and the EAT volumes were comparable between those with and without DM. Both patient groups showed comparable MBF at rest and coronary vascular resistance. A lower hyperemic MBF and coronary flow reserve (CFR) and greater hyperemic coronary vascular resistance (all p <0.05) was observed in the patients with DM. A pooled analysis showed a positive association of EAT volume with hyperemic coronary vascular resistance but not with the MBF at rest, hyperemic MBF, or coronary vascular resistance at rest. In the group analysis, the EAT volume was inversely associated with hyperemic MBF (r = -0.16, p = 0.05) and CFR (r = -0.17, p = 0.04) and positively with hyperemic coronary vascular resistance (r = 0.26, p = 0.002) only in patients without DM. Multivariate regression analysis, adjusted for age, gender, and body mass index, showed an independent association between the EAT volume and hyperemic MBF (β = -0.16, p = 0.02), CFR (β = -0.16, p = 0.04), and hyperemic coronary vascular resistance (β = 0.25, p <0.001) in the non-DM group. In conclusion, these results suggest a role for EAT in myocardial microvascular dysfunction; however, once DM has developed, other factors might be more dominant in contributing to impaired myocardial microvascular dysfunction.

Assessment of coronary microvascular resistance in the chronic infarcted pig heart

Pre-clinical studies aimed at treating ischemic heart disease (i.e. stem cell- and growth factor therapy) often consider restoration of the impaired microvascular circulation as an important treatment goal. However, serial in vivo measurement hereof is often lacking. The purpose of this study was to evaluate the applicability of intracoronary pressure and flow velocity as a measure of microvascular resistance in a large animal model of chronic myocardial infarction (MI). Myocardial infarction was induced in Dalland Landrace pigs (n = 13; 68.9 ± 4.1 kg) by a 75-min. balloon occlusion of the left circumflex artery (LCX). Intracoronary pressure and flow velocity parameters were measured simultaneously at rest and during adenosine-induced hyperemia, using the Combowire (Volcano) before and 4 weeks after MI. Various pressure- and/or flow-derived indices were evaluated. Hyperemic microvascular resistance (HMR) was significantly increased by 28% in the infarct-related artery, based on a significantly decreased peak average peak flow velocity (pAPV) by 20% at 4 weeks post-MI (P = 0.03). Capillary density in the infarct zone was decreased compared to the remote area (658 ± 207/mm2 versus 1650 ± 304/mm2, P = 0.017). In addition, arterioles in the infarct zone showed excessive thickening of the alpha smooth muscle actin (αSMA) positive cell layer compared to the remote area (33.55 ± 4.25 μm versus 14.64 ± 1.39 μm, P = 0.002). Intracoronary measurement of HMR successfully detected increased microvascular resistance that might be caused by the loss of capillaries and arteriolar remodelling in the chronic infarcted pig heart. Thus, HMR may serve as a novel outcome measure in pre-clinical studies for serial assessment of microvascular circulation.

Coronary flow reserve is impaired in infarcted as well as normal myocardium following successful PCI in patients with acute myocardial infarction

Purpose: Data about evolution of microvascular function in the myocardium after successful percutaneous coronary intervention (PCI) are scarce. This holds true not only for the infarcted area but also for the remote zone. Insight in such data would lead to better understanding of the recovery of left ventricular function (LVF) after acute myocardial infarction (AMI). Also, it will guide interpretation of perfusion imaging early after myocardial infarction. Methods: We studied 25 patients (mean age 58±8 years, 21 men) presenting with an acute ST-elevation myocardial infarction (STEMI) after they were treated successfully by primary PCI. Using a hybrid positron-emission tomography/computed tomography (PET/CT) scanner, myocardial blood flow (MBF) was measured in the infarcted and normal remote area using [15O]H2O (at rest and during adenosine-induced hyperemia). To investigate the evolution of myocardial microvascular function, we performed scans at 5±3 days (1-week study) and 3±1 months (3-month study) after successful PCI. Results: At one week, baseline MBF was 0.95±0.18 ml/min/g in the infarct-related artery and 1.01±0.29 in the remote region (P=0.130), hyperemic MBF was 1.70±0.53 vs. 2.20±0.47 (P<0.001) and the coronary flow reserve (CFR; the ratio of the MBF after induction of hyperemia to basal blood flow) was 1.80±0.62 vs. 2.29±0.65 (P=0.001). At three months, baseline MBF was 0.80±0.16 ml/min/g in the infarct-related artery and 0.95±0.20 in the remote region (P=0.003), hyperemic MBF was 2.10±0.80 vs. 2.62±0.75 (P<0.001) and CFR was 2.68±0.96 vs. 2.86±0.87 (P=0.181 for the comparison with the infarcted region; P<0.001 for the comparison with the infarcted region at 1 week; P=0.004 for the comparison with the remote region at 1 week). Conclusion: Following successful PCI in patients with acute myocardial infarction, the coronary flow reserve is severely affected. Our findings show a transient microvascular coronary dysfunction in remote myocardium following acute myocardial infarction. This observation may have implications for imaging in an early stadium following myocardial infarction.

The impact of gender on fractional flow reserve measurements

Fractional flow reserve (FFR) allows accurate investigation of the functional significance of intermediate coronary stenoses. The present study set out to study the impact of gender on FFR measurements. Three hundred and seventeen intermediate (40-70% at angiography) stenoses were assessed with FFR in 270 patients (mean age 65.8 ± 10.3 years, 84 females). Resting Pd/Pa (the ratio of mean blood pressure measured distal to the stenosis to mean aortic blood pressure in resting conditions), FFR (Pd/Pa during adenosine-induced hyperaemia) and the ΔPd/Pa (calculated as the change in Pd/Pa during hyperaemia) were measured. There was no difference in the location and degree of stenoses between genders (p>0.5). Similarly, there was no difference in age and in the prevalence of cardiovascular risk factors (all p>0.2). Resting Pd/Pa also did not differ between genders (0.92 ± 0.08 vs. 0.93 ± 0.05, p=0.23). In response to adenosine, however, a significantly larger ΔPd/Pa (0.14 ± 0.07 vs. 0.11 ± 0.07, p=0.001) and a significantly lower FFR (0.79 ± 0.12 vs. 0.82 ± 0.10, p=0.008) were observed in males. This difference was maintained in a multivariate regression analysis. We observed gender-based differences in FFR data in daily routine. Further studies are necessary to test the mechanism of this observation and how these differences impact on the assessment of haemodynamically relevant stenoses.

Myocardial perfusion pressure in patients with hypertension and coronary artery disease

The target blood pressure (BP) in patients with hypertension and coronary artery disease (CAD) has been controversial. Whether patients with both diabetes mellitus and CAD should follow targets for either diabetes mellitus or CAD is uncertain. Focusing only on one determinant of coronary blood flow (CBF) - myocardial perfusion pressure (MPP) - coronary BP in patients with hypertension was used to estimate the impact of setting BP targets. A consecutive series of 101 patients referred for coronary angiography for stable angina pectoris or possible CAD had BP measurements proximal and distal to coronary artery stenosis. Fractional flow reserve (FFR) was measured from adenosine-induced maximal hyperemia. DBP after the coronary stenosis was the MPP. The most severe coronary lesion for each person was selected. Of 101 patients, 65.0 ± 10.6 years (mean ± SD), there were 69 with hypertension and 33 with diabetes mellitus of whom 25 had diabetes mellitus along with hypertension. In hypertension, FFR was 0.83 ± 0.08, range from 0.49 to 0.97, with 40% having FFR less than 0.8. There was a significant linear relationship between systemic DBP and MPP. CBF approximates zero with MMP of 50 mmHg under resting conditions and 40 mmHg with coronary vasodilatation. On the basis of our findings in hypertension, if DBP were 80, 70, 65 and 60 mmHg, 1.4, 7.1, 15.7 and 54.3%, respectively, of patients would have an MPP of less than 50 mmHg. The values were similar for patients with diabetes mellitus. In our patient group with moderate coronary artery stenosis, a target DBP of 60 mmHg or less would be associated with unacceptably low MPPs. In patients with diabetes mellitus, the presence and severity of CAD stenosis may be more important factor in setting BP targets for treatment of hypertension. Because the degree of coronary stenosis is unknown in most patients with hypertension and CAD, guideline recommendations should consider cautioning clinicians about the potential for myocardial ischaemia at low DBP.

General Anesthesia with Sevoflurane Decreases Myocardial Blood Volume and Hyperemic Blood Flow in Healthy Humans

Preservation of myocardial perfusion during general anesthesia is likely important in patients at risk for perioperative cardiac complications. Data related to the influence of general anesthesia on the normal myocardial circulation are limited. In this study, we investigated myocardial microcirculatory responses to pharmacological vasodilation and sympathetic stimulation during general anesthesia with sevoflurane in healthy humans immediately before surgical stimulation. Six female and 7 male subjects (mean age 43 years, range 28-61) were studied at baseline while awake and during the administration of 1 minimum alveolar concentration sevoflurane. Using myocardial contrast echocardiography, myocardial blood flow (MBF) and microcirculatory variables were assessed at rest, during adenosine-induced hyperemia, and after cold pressor test-induced sympathetic stimulation. MBF was calculated from the relative myocardial blood volume multiplied by its exchange frequency (β) divided by myocardial tissue density (ρT), which was set at 1.05 g·mL(-1). During sevoflurane anesthesia, MBF at rest was similar to baseline values (1.05 ± 0.28 vs 1.05 ± 0.32 mL·min(-1)·g(-1); P = 0.98; 95% confidence interval [CI], -0.18 to 0.18). Myocardial blood volume decreased (P = 0.0044; 95% CI, 0.01-0.04) while its exchange frequency (β) increased under sevoflurane anesthesia when compared with baseline. In contrast, hyperemic MBF was reduced during anesthesia compared with baseline (2.25 ± 0.5 vs 3.53 ± 0.7 mL·min(-1)·g(-1); P = 0.0003; 95% CI, 0.72-1.84). Sympathetic stimulation during sevoflurane anesthesia resulted in a similar MBF compared to baseline (1.53 ± 0.53 and 1.55 ± 0.49 mL·min(-1)·g(-1); P = 0.74; 95% CI, -0.47 to 0.35). In otherwise healthy subjects who are not subjected to surgical stimulation, MBF at rest and after sympathetic stimulation is preserved during sevoflurane anesthesia despite a decrease in myocardial blood volume. However, sevoflurane anesthesia reduces hyperemic MBF, and thus MBF reserve, in these subjects.

Effects of anabolic steroid use on myocardial perfusion in body-builders: a quantitative cardiovascular magnetic resonance Study

Methods Twenty one body-builders were studied 14 anabolic steroid users and 7 controls matched for age and training history. First pass CMR perfusion imaging was performed on a 1.5T Avanto (Siemens, Erlangen, Germany) after adenosine-induced hyperemia (140 mcg/kg/min) and at rest using a hybrid echo-planar imaging sequence. Images of the base, mid-ventricle and apex were acquired and the myocardium was divided into 16 segments as well as endocardial and epicardial layers. After image registration, a modified Fermi-constrained deconvolution algorithm was applied pixel-wise to quantify absolute MBF. Late gadolinium enhancement (LGE) imaging was performed as well as standard assessment of ventricular volumes, function and LV mass. Data were analysed using a linear mixed effects model.

Comprehensive phenotyping of salt-induced hypertensive heart disease in living mice using cardiac magnetic resonance

To characterise the effects of high-salt diet (HSD) on left ventricular (LV) mass, systolic function and coronary reserve in living mice using cardiac magnetic resonance imaging (MRI). Thirty C57BL/6 1-month-old female mice were fed either a control (n = 15) or an HSD (n = 15). After 3 months, LV volumes, ejection fraction and mass were assessed using time-resolved three-dimensional (3D) black-blood manganese-enhanced MRI, and coronary flow velocity reserve (CFVR) was assessed using dynamic MR angiography at rest and during adenosine-induced hyperaemia. Hearts were excised to assess LV wet mass and micro-vascular remodelling at histology. Micro-vascular remodelling was found at histology in all investigated hearts from the HSD group and none from the control group. No difference between the HSD and control groups was found in terms of heart weight, LV volumes and ejection fraction. Heart to body weight ratio was higher in the HSD group (4.39 ± 0.24 vs 4.02 ± 0.16 mg/g, P < 0.001), because of lower body weight (22.3 ± 0.9 vs 24.0 ± 1.4 g, P < 0.001). CFVR was lower in the HSD group (1.73 ± 0.11 vs 1.94 ± 0.12, P < 0.001). Phenotyping of hypertensive heart disease is feasible in living mice using dynamic MR angiography and time-resolved 3D black-blood manganese-enhanced MRI. HSD is associated with early impairment of coronary reserve, before the onset of significant hypertrophy.

Evaluation of the endothelial function in hypertensive patients with 13N-ammonia PET

BackgroundEssential hypertension is one of the main risk factors for the development of coronary artery disease (CAD). Hypertension causes endothelial dysfunction which is considered an early sign for the development of CAD. Positron emission tomography is a non-invasive imaging technique that measures myocardial blood flow (MBF), allowing us to identify patients with endothelial dysfunction. Methods and Results19 patients without comorbidities recently diagnosed hypertensive, as well as 21 healthy volunteers were studied. A three-phase (rest, cold pressor test, and adenosine-induced hyperemia) 13N-ammonia PET was performed, and MBF was measured. Endothelial-Dependent Vasodilation Index, ΔMBF, and coronary flow reserve (CFR) were calculated for each patient. Hypertensive patients had a significantly higher systolic and diastolic blood pressures compared with the control group (134.6 ± 11.7/86.4 ± 10.6 mm Hg and 106.0 ± 11.8/71.4 ± 6.6 mm Hg, respectively, P < .001). The ENDEVI (1.28 ± 0.26 vs 1.79 ± 0.30, P < .001), the ΔMBF (0.81 ± 0.50 vs 0.25 ± 0.21, P < .001) and the CFR (2.18 ± 0.88 vs 3.17 ± 0.68, P = .001) were significantly lower in the hypertensive patients compared to the control group, 84% of the former group had endothelial dysfunction i.e., ENDEVI < 1.5 and 58% had vasomotor abnormalities, i.e., CFR < 2.5. ConclusionsIn this study, we showed that recently diagnosed hypertensive patients have coronary endothelial dysfunction and vasomotor disturbances which are early signs for the development of CAD.

133 Coronary wave intensity: a novel invasive tool for predicting myocardial viability following acute coronary syndromes

IntroductionWave intensity analysis (WIA) uses simultaneous changes in intracoronary pressure and flow to characterise energy transfer within the coronary circulation. In normal hearts, flow is predominantly driven by a microcirculatory-derived,...

Quantification of myocardial blood flow with 82Rb positron emission tomography: clinical validation with 15O-water

PurposeQuantification of myocardial blood flow (MBF) with generator-produced 82Rb is an attractive alternative for centres without an on-site cyclotron. Our aim was to validate 82Rb-measured MBF in relation to that measured using 15O-water, as a tracer 100% of which can be extracted from the circulation even at high flow rates, in healthy control subject and patients with mild coronary artery disease (CAD).MethodsMBF was measured at rest and during adenosine-induced hyperaemia with 82Rb and 15O-water PET in 33 participants (22 control subjects, aged 30 ± 13 years; 11 CAD patients without transmural infarction, aged 60 ± 13 years). A one-tissue compartment 82Rb model with ventricular spillover correction was used. The 82Rb flow-dependent extraction rate was derived from 15O-water measurements in a subset of 11 control subjects. Myocardial flow reserve (MFR) was defined as the hyperaemic/rest MBF. Pearson’s correlation r, Bland-Altman 95% limits of agreement (LoA), and Lin’s concordance correlation ρ c (measuring both precision and accuracy) were used.ResultsOver the entire MBF range (0.66–4.7 ml/min/g), concordance was excellent for MBF (r = 0.90, [82Rb–15O-water] mean difference ± SD = 0.04 ± 0.66 ml/min/g, LoA = −1.26 to 1.33 ml/min/g, ρ c = 0.88) and MFR (range 1.79–5.81, r = 0.83, mean difference = 0.14 ± 0.58, LoA = −0.99 to 1.28, ρ c = 0.82). Hyperaemic MBF was reduced in CAD patients compared with the subset of 11 control subjects (2.53 ± 0.74 vs. 3.62 ± 0.68 ml/min/g, p = 0.002, for 15O-water; 2.53 ± 1.01 vs. 3.82 ± 1.21 ml/min/g, p = 0.013, for 82Rb) and this was paralleled by a lower MFR (2.65 ± 0.62 vs. 3.79 ± 0.98, p = 0.004, for 15O-water; 2.85 ± 0.91 vs. 3.88 ± 0.91, p = 0.012, for 82Rb). Myocardial perfusion was homogeneous in 1,114 of 1,122 segments (99.3%) and there were no differences in MBF among the coronary artery territories (p > 0.31).ConclusionQuantification of MBF with 82Rb with a newly derived correction for the nonlinear extraction function was validated against MBF measured using 15O-water in control subjects and patients with mild CAD, where it was found to be accurate at high flow rates. 82Rb-derived MBF estimates seem robust for clinical research, advancing a step further towards its implementation in clinical routine.

Looking for Myocardial Viability After a STICH Trial: Not Enough to Close the Door

349 Objectives Cardiac allograft vasculopathy (CAV) is a rapidly progressive form of atherosclerosis and an important determinant of long-term survival. The aim of the study was to investigate the value of longitudianl follow-up of 13N-ammonia PET in patients after heart transplantation. Methods A total 22 cardiac recipients (16 men, age 46±12y) underwent at least two 13N-ammonia PET studies between Jan 2007 and Dec 2011. All patients had preserved left ventricular ejection fraction (≥50%) and normal coronary angiogram initially. Myocardial blood flow (MBF) was assessed using dynamic PET at rest and adenosine-induced hyperemia, and myocardial perfusion reserve (MPR) was calculated as the ratio of hyperemic MBF to resting MBF. The quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS) measurements for plaque volume index ([total plaque volume/total vessel volume] ×100%) and maximum area of stenosis were compared with MPR. Results MPR correlated inversely with IVUS parameters (r=0.39, p Conclusions The findings of this study suggest that quantitative measurement of myocardial flow using dynamic 13N-ammonia PET is feasible and more sensitive for CAV assessment, and could be used as a useful marker of disease progression and therapy guidance. Research Support NSC 100-2314-B-002 -15

Effect of tracer arrival time on the estimation of the myocardial perfusion in DCE-CMR

Background An accurate segmental myocardial blood flow (MBF) quantification can be performed by means of signal deconvolution techniques. The accuracy of MBF estimates relies on the precise identification of the tracer arrival time in the myocardium (tOnset). Voxelwise MBF quantification is likel yt o be more subject to such error than segmental MBF analysis due to the lower signal-to-noise ratio of myocardial signal intensity curves. Automated tOnset detection methods would be therefore warranted. The aim of this study was to assess the importance to of tOnset identification on voxelwise MBF quantification and to describe an automated algorithm to detect the optimal tOnset which minimizes the error in MBF estimates. Methods Perfusion data were obtained from an hardware perfusion phantom (validated MBF 5 ml/g/min) and from patients during adenosine-induced hyperaemia (140µg/ kg/min) using 0.075mmol/kg Gadobutrol (Gadovist, Schering, Germany) injected at 4ml/minute followed by a 20 ml saline flush. A pre-bolus technique was used for quantification.