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Philipp A Kaufmann

Publications and source records attributed to Philipp A Kaufmann.

31 records · Page 2Linked to original sources
PubMed2005

Novel doppler assessment of intracoronary volumetric flow reserve: validation against PET in patients with or without flow-dependent vasodilation.

UNLABELLED: Volumetric blood flow (Q) determination requires simultaneous assessment of mean blood flow velocity and vessel cross-sectional area. At present, no method provides both values. Intracoronary Doppler-based assessment of coronary flow velocity reserve (CFVR) relies on average peak velocity (APV). Because this does not account for changes in velocity profile or vessel area usually occurring with flow-dependent vasodilation, results can be misleading. The aim of this clinical study was to validate against the current gold standard (measurement of myocardial perfusion reserve [MPR] by PET) a new, Doppler-based method for calculating coronary Q and coronary flow reserve (CFR). METHODS: Doppler-based intracoronary Q was measured with a proprietary guidewire device in a nonstenotic coronary artery at baseline and during adenosine-induced hyperemic flow (140 mug/kg/min intravenously during 7 min). Three gate positions were assessed, of which 2 were lying within the vessel and 1 was intersecting the vessel. The zeroth (M(0)) and the first (M(1)) Doppler moments of the intersecting gate were used to calculate mean blood flow velocity (M(1)/M(0)) and vessel area (M(0)), and M(0) of the 2 proximal gates was used to correct for scattering and attenuation. CFR was calculated as hyperemic/resting flow with Q and compared with APV-derived CFVR and with the corresponding segmental MPR obtained with (15)O-labeled water and PET. RESULTS: Q (CFR, 2.60 +/- 1.07) correlated well with PET (MPR, 2.58 +/- 1.11) (r = 0.832, P < 0.005; Bland-Altman limits, -1.42 to 1.09), whereas CFVR did not (r = 0.09, P = not statistically significant; Bland-Altman limits, -3.36 to 2.24). However, in vessels without dilation, there was no difference between CFR, CFVR, and MPR. CONCLUSION: This procedure for intracoronary Q measurement using the proprietary Doppler guidewire system, which accounts for both changes in flow profile and changes in vessel area, allows invasive, accurate assessment of CFR even in the presence of flow-dependent vasodilation.

Adult↗
PubMed2004

Systemic inhibition of nitric oxide synthase unmasks neural constraint of maximal myocardial blood flow in humans.

BACKGROUND: Nitric oxide (NO) is an endothelial mediator that regulates vascular smooth muscle tone, but it may exert its cardiovascular action also by modulating the autonomic control of vasomotor tone. We assessed the effect of simultaneous inhibition of both endothelial (eNOS) and neuronal (nNOS) NO synthase isoforms on myocardial blood flow (MBF) and coronary flow reserve (CFR) in volunteers and in (denervated) transplant recipients. METHODS AND RESULTS: MBF (mL x min(-1) x g(-1)) was measured at rest and during adenosine-induced hyperemia with positron emission tomography and 15O-labeled water. CFR was calculated as adenosine/resting MBF. Measurements were repeated during one of the following intravenous infusions: group 1 (n=12), saline; group 2 (n=9), 3 mg/kg N(G)-monomethyl-L-arginine (L-NMMA), which crosses the blood-brain barrier and inhibits both eNOS and nNOS; group 3 (n=13), 10 mg/kg L-NMMA; group 4 (n=8), phenylephrine titrated to simulate the hemodynamic changes in group 3; and group 5 (n=6), 10 mg/kg L-NMMA infused into the heart transplant recipients. After intervention, hyperemic MBF and CFR were unchanged in groups 1, 2, and 4. By contrast, both hyperemic MBF (+53%, P<0.0001 versus baseline) and CFR (+52%, P<0.0001 versus baseline) increased in group 3, whereas they remained unchanged in group 5, which suggests that an intact cardiac innervation was required for the increase in MBF and CFR observed in group 3. CONCLUSIONS: The results of the present study suggest that maximal adenosine-induced hyperemia and CFR in humans are constrained by neurally mediated vasoconstriction, which can be relieved by systemic NOS inhibition with L-NMMA.

Adenosine↗
PubMed2004

Tetrahydrobiopterin restores impaired coronary microvascular dysfunction in hypercholesterolaemia.

PURPOSE: Tetrahydrobiopterin (BH4) is an essential co-factor for the synthesis of nitric oxide (NO), and BH4 deficiency may cause impaired NO synthase (NOS) activity. We studied whether BH4 deficiency contributes to the coronary microcirculatory dysfunction observed in patients with hypercholesterolaemia. METHODS: Myocardial blood flow (MBF; ml min(-1) g(-1)) was measured at rest, during adenosine-induced (140 microg kg(-1) min(-1) over 7 min) hyperaemia (mainly non-endothelium dependent) and immediately after supine bicycle exercise (endothelium-dependent) stress in ten healthy volunteers and in nine hypercholesterolaemic subjects using 15O-labelled water and positron emission tomography. Measurements were repeated 60 min later, after intravenous infusion of BH4 (10 mg kg(-1) body weight over 30 min). Adenosine-induced hyperaemic MBF is considered to represent (near) maximal flow. Flow reserve utilisation was calculated as the ratio of exercise-induced to adenosine-induced hyperaemic MBF and expressed as percent to indicate how much of the maximal (adenosine-induced) hyperaemia can be achieved by bicycle stress. RESULTS: BH4 increased exercise-induced hyperaemia in controls (2.96+/-0.58 vs 3.41+/-0.73 ml min(-1) g(-1), p<0.05) and hypercholesterolaemic subjects (2.47+/-0.78 vs 2.70+/-0.72 ml min(-1) g(-1), p<0.01) but had no influence on MBF at rest or during adenosine-induced hyperaemia in controls (4.52+/-1.10 vs 4.85+/-0.45 ml min(-1) g(-1), p=NS) or hypercholesterolaemic subjects (4.86+/-1.18 vs 4.53+/-0.93 ml min(-1) g(-1), p=NS). Flow reserve utilisation remained unchanged in controls (70+/-17% vs 71+/-19%, p=NS) but increased significantly in hypercholesterolaemic subjects (53+/-15% vs 66+/-14%, p<0.05). CONCLUSION: BH4 restores flow reserve utilisation of the coronary microcirculation in hypercholesterolaemic subjects, suggesting that BH4 deficiency may contribute to coronary microcirculatory dysfunction in hypercholesterolaemia.

Adult↗
PubMed2004

Regional myocardial ischemia in hypertrophic cardiomyopathy: impact of myectomy.

OBJECTIVE: Chest pain is a common finding in patients with hypertrophic cardiomyopathy and can be observed in 40% to 50% of all patients. However, the pathogenesis of these ischemia-like symptoms is still unclear. METHODS: Twenty-two patients with hypertrophic cardiomyopathy and 15 controls underwent positron emission tomography for evaluation of regional myocardial perfusion and coronary flow reserve (hyperemic/baseline myocardial blood flow). Myocardial perfusion (mL/min/g) was measured using [(13)N]ammonia at rest and during hyperemia with dipyridamole (0.56 mg/kg intravenously). Regional coronary flow reserve was assessed in 3 planes (apical, midventricular, basal) in 4 regions (septal, anterior, lateral, inferior). Patients were divided into 2 groups: group 1 consisted of 11 patients treated with surgical myectomy (age 56 +/- 10 years) and group 2 consisted of 11 patients treated medically (age 53 +/- 13 years). RESULTS: Mean global coronary flow reserve was 3.87 +/- 0.92 in controls but 2.31 +/- 0.40 in operated (P <.001 vs controls) and 1.76 +/- 0.58 in medically treated patients (P <.001 vs controls, P <.05 vs operated). Similarly, septal coronary flow reserve was 4.19 +/- 1.22 in controls but significantly reduced in operated patients (2.26 +/- 0.48, P <.001 vs controls) and in medically treated patients (1.76 +/- 0.58; P <.001 vs controls). However, septal flow reserve was significantly higher in operated patients than in patients with medically treated hypertrophic cardiomyopathy (+37%, P <.05), mainly due to a reduced resting myocardial perfusion. CONCLUSIONS: Global and regional myocardial perfusion is reduced in patients with hypertrophic cardiomyopathy. However, myectomy may have a beneficial effect on septal perfusion and flow reserve. Thus, ischemia seems to play an important role in the symptomatology and pathophysiology of hypertrophic cardiomyopathy.

Cardiomyopathy, Hypertrophic↗
PubMed2004

A novel in vivo procedure for volumetric flow measurements.

We report on a novel procedure for invasive volumetric blood flow measurements using a commercially available Doppler flow wire system, which could, until now, only measure flow velocity. We here describe a method applicable in vivo to generate both velocity and cross-sectional area information from the same pulsed-wave Doppler signal for volumetric flow assessment. We demonstrate its feasibility and validation in vivo in pig coronary arteries. Our Doppler-derived volumetric flow measurements were compared with the respective transit-time flow and showed an excellent correlation (r = 0.969; p < 0.0001). Agreement between transit-time and Doppler-derived flow measurements could be observed for flow conditions ranging from 30 to 180 mL/min. The mean values for the two methods were 71.4 +/- 43.7 mL/min and 71.3 +/- 42.2 mL/min, respectively. We conclude that this technique might possibly be introduced into future clinical practice as an invasive procedure of choice for the assessment of volumetric blood flow.

Animals↗
PubMed2004

CT attenuation correction for myocardial perfusion quantification using a PET/CT hybrid scanner.

UNLABELLED: In routine PET, a 10- to 20-min transmission scan with a rotating (68)Ge source is commonly obtained for attenuation correction (AC). AC is time-consuming using this procedure and could considerably be shortened by instead using a rapid CT scan. Our aim was to evaluate the feasibility of CT AC in quantitative myocardial perfusion PET using a hybrid PET/CT scanner. METHODS: (13)N-labeled NH(3) and PET were used to measure myocardial blood flow (MBF) (mL/min/g) at rest and during standard adenosine stress. In group 1 (n = 7), CT scans (0.5 s) of the heart area with different tube currents (10, 40, 80, and 120 mA) were compared with a standard (68)Ge transmission (20 min) and with no AC. In group 2 (n = 3), the repeatability of 8 consecutive CT scans at a tube current of 10 mA was assessed. In group 3 (n = 4), emission was preceded and followed by 3 CT scans (10 mA) and 1 (68)Ge scan for each patient. For reconstruction, filtered backprojection (FBP) was compared with iterative reconstruction (IT). RESULTS: For group 1, no significant difference in mean MBF for resting and hyperemic scans was found when emission reconstructed with (68)Ge AC was compared with emission reconstructed with CT AC at any of the different tube currents. Only emission without any correction differed significantly from (68)Ge AC. For group 2, repeated measurements revealed a coefficient of variance ranging from 2% to 5% and from 2% to 6% at rest and at stress, respectively. For group 3, similar reproducibility coefficients (RC) for MBF were obtained when (68)Ge AC(FBP) was compared with (68)Ge AC(IT) (RC = 0.218) and when CT AC(FBP) was compared with CT AC(IT) (RC = 0.227). Even better reproducibility (lower RC) was found when (68)Ge AC(FBP) was compared with CT AC(FBP) (RC = 0.130) and when (68)Ge AC(IT) was compared with CT AC(IT) (RC = 0.146). CONCLUSION: Our study shows that for the assessment of qualitative and quantitative MBF with a hybrid PET/CT scanner, the use of CT AC (with a tube current of 10 mA) instead of (68)Ge AC provides accurate results.

Algorithms↗
PubMed2004

Gated (99m)Tc-tetrofosmin SPECT for discriminating infarct from artifact in fixed myocardial perfusion defects.

UNLABELLED: Soft-tissue attenuation artifacts generally appear as fixed perfusion-scan defects. Gated (99m)Tc-tetrofosmin SPECT may help differentiate myocardial infarction (MI) from artifacts, as fixed defects with decreased function (wall motion and thickening) probably represent MI, whereas attenuation artifacts represent preserved function. METHODS: Ungated stress and gated rest (99m)Tc-tetrofosmin SPECT was performed on 153 consecutive patients referred for evaluation of coronary artery disease. From stress and summed gated rest images, 107 patients (70%) were identified with isolated fixed defects. The function of the defects was assessed semiquantitatively from gated stress images. The findings were correlated with clinical (history or electrocardiographic Q waves) evidence of MI. RESULTS: Of 62 patients with fixed defects and clinical MI, 60 (97%) had an abnormal defect function. Of 45 patients with no clinical MI, 16 (36%) had decreased function of the defect, possibly indicating silent MI. In 29 of the 45 patients (64%) with no clinical MI, defect function was normal. Because most (90%) fixed defects with normal systolic function occurred in men with inferior fixed defects (87%) or women with anterior fixed defects (3%), these were most likely attenuation artifacts. By reclassifying the condition of patients with fixed defects and normal function as normal, patients with unexplained fixed defects (no clinical MI) decreased from 29% to 10%. CONCLUSION: Gating adds considerable value to (99m)Tc-tetrofosmin SPECT myocardial perfusion imaging in characterizing fixed defects and potentially improves test specificity.

Adenosine↗
PubMed2004

Beta-adrenergic blockade and myocardial perfusion in coronary artery disease: differential effects in stenotic versus remote myocardial segments.

UNLABELLED: Beta-adrenergic blocking agents are widely used in coronary artery disease (CAD), although their impact on myocardial blood flow (MBF) and coronary flow reserve (CFR) remains unclear. We studied the effect of long-term beta-blocker treatment (carvedilol or metoprolol) on coronary microcirculation in CAD patients using PET. METHODS: Regional and global resting and adenosine-induced hyperemic MBF and CFR were measured with 13N-ammonia and PET in 36 CAD patients before and after 12 wk of oral therapy with either carvedilol, 50 mg/d, or metoprolol, 100 mg/d. RESULTS: Beta-blockade decreased global resting MBF in proportion to cardiac work (from 0.86 +/- 0.20 to 0.77 +/- 0.14 mL/min/g, P < 0.05) without affecting global hyperemic flow. Hyperemic MBF was significantly lower in stenosis-dependent segments than in remote segments (1.76 +/- 0.64 vs. 2.04 +/- 0.67 mL/min/g, P < 0.05) at baseline but was comparable in both after treatment (2.02 +/- 0.68 vs. 1.90 +/- 0.78 mL/min/g, P = not statistically significant [NS]), resulting in a significant CFR increase in stenotic segments (+15%, P < 0.05) but not in remote segments (+9%, P = NS). CONCLUSION: The beneficial effect of beta-adrenergic blockade can be explained by the reduction in oxygen consumption (= decreased demand) but also by a modest improvement in vasodilator capacity (= increased supply). The improvement in CFR is found predominantly in stenosis-dependent rather than remote segments.

Adrenergic beta-Antagonists↗
PubMed2003

Influence of altitude exposure on coronary flow reserve.

BACKGROUND: Although no data exist on the effect of altitude exposure on coronary flow reserve (CFR), patients with coronary artery disease (CAD) are advised not to exceed moderate altitudes of approximately 2500 m above sea level. We studied the influence of altitude on myocardial blood flow (MBF) in controls and CAD patients. METHODS AND RESULTS: In 10 healthy controls and 8 patients with CAD, MBF was measured by positron emission tomography and 15O-labeled water at rest, during adenosine stress, and after supine bicycle exercise. This protocol was repeated during inhalation of a hypoxic gas mixture corresponding to an altitude of 4500 m (controls) and 2500 m (CAD). Workload was targeted to comparable heart rate-blood pressure products at normoxia and hypoxia. Resting MBF increased significantly in controls at 4500 m (+24%, P<0.01) and in CAD patients at 2500 m (+24%, P<0.05). Altitude had no influence on adenosine-induced hyperemia and CFR. Exercise-induced hyperemia increased significantly in controls (+38%, P<0.01) at 4500 m (despite a reduction in workload, -28%, P<0.0001) but not in CAD patients at 2500 m (moderate decrease in workload, -11%, P<0.05). Exercise-induced reserve was preserved in controls (+10%, P=NS) but decreased in CAD patients (-18%, P<0.005). CONCLUSIONS: At 2500 m altitude, there is a significant decrease in exercise-induced reserve in CAD patients, indicating that compensatory mechanisms might be exhausted even at moderate altitudes, whereas healthy controls have preserved reserve up to 4500 m. Thus, patients with CAD and impaired CFR should be cautious when performing physical exercise even at moderate altitude.

Adult↗
PubMed2003

Bicycle exercise stress in PET for assessment of coronary flow reserve: repeatability and comparison with adenosine stress.

UNLABELLED: PET allows absolute measurements of myocardial blood flow (MBF). The aim of the present study was to evaluate the feasibility and repeatability of supine bicycle exercise stress, compared with standard adenosine stress, in PET. METHODS: In 11 healthy volunteers, MBF was assessed at rest, during adenosine-induced (140 microg/kg/min over 7 min) hyperemia, and immediately after supine bicycle exercise (mean workload, 130 W, which is 70% of the predicted value) using PET and (15)O-H(2)O. The assessment was then repeated after 20 min. Coronary flow reserve (CFR) was calculated as hyperemic/resting MBF for adenosine stress and exercise stress. Repeatability was evaluated according to the method of Bland and Altman. RESULTS: No significant differences were found between the paired resting MBF (1.22 +/- 0.16 vs. 1.26 +/- 0.21 mL/min/g; mean difference, 3% +/- 11%) and the hyperemic MBF with adenosine stress (5.13 +/- 0.74 vs. 4.97 +/- 1.05; mean difference, -4% +/- 14%) or exercise stress (2.35 +/- 0.66 vs. 2.25 +/- 0.61; mean difference, -4% +/- 19%). CFR was reproducible with adenosine stress (4.23 +/- 0.62 vs. 4.05 +/- 1.06, P = not statistically significant; mean difference, -5% +/- 19%) and exercise stress (1.91 +/- 0.46 vs. 1.80 +/- 0.44, P = not statistically significant; mean difference, -5% +/- 15%). Repeatability coefficients for MBF were 0.26 (rest), 1.34 (adenosine stress), and 0.82 (exercise stress) mL/min/g. CONCLUSION: Assessment of CFR with (15)O-H(2)O and PET using bicycle exercise in the PET scanner is feasible and at least as repeatable as using adenosine stress.

Adenosine↗
PubMed2002

Isolated ventricular noncompaction is associated with coronary microcirculatory dysfunction.

OBJECTIVES: We sought to analyze whether a microcirculatory dysfunction might be associated with isolated ventricular noncompaction (IVNC). BACKGROUND: In IVNC, which is a cardiomyopathy thus far "unclassified" by the World Health Organization, heart failure and sudden cardiac death are common findings, but the pathophysiologic mechanisms are unknown. METHODS: In 12 patients with IVNC and 14 control subjects, quantitative evaluation of regional myocardial perfusion (myocardial blood flow [MBF]) and coronary flow reserve (CFR, hyperemic/baseline MBF) was performed using positron emission tomography and (13)N-ammonia. The left ventricular myocardium was divided into nine segments, and the two-dimensional echocardiogram in each patient with IVNC was compared with CFR in each segment. Noncompaction was defined as a two-layered structure with excessive trabeculation. RESULTS: The CFR in control subjects averaged 4.2+/-0.9, providing a cut-off value > or =2.5, but it was 2.1+/-0.8 in patients with IVNC. A perfusion scan defect was found in 14 of 24 segments with noncompaction, although no defect was found in 76 of 84 normal segments (overall agreement 83%, p < 0.0001 by the chi-square test). In 16 of 21 segments with noncompaction, a decreased CFR was found; but a decreased CFR was also found in 36 of 60 segments without noncompaction (p = NS). In 45 of the 57 segments with wall motion abnormalities, CFR was decreased, but it was preserved in 17 of the 24 segments with normal wall motion (agreement 77%, p < 0.0001). CONCLUSIONS: In patients with IVNC, a decreased CFR is not confined to noncompacted segments, but extends to most segments with wall motion abnormalities. Thus, coronary microcirculatory dysfunction is associated with IVNC.

Adult↗