Patrick T. Siegrist

Interaction of caffeine with regadenoson-induced hyperemic myocardial blood flow as measured by positron emission tomography: a randomized, double-blind, placebo-controlled crossover trial.

To the Editor: Regadenoson is a selective A2A adenosine receptor agonist under investigation as a pharmacologic vasodilator in nuclear stress myocardial perfusion imaging (MPI) ([1][1]). It has a higher affinity for A2A receptors than adenosine and is a more potent coronary vasodilator. It

Left bundle branch block causes relative but not absolute septal underperfusion during exercise

AIMS Left bundle branch block (LBBB) often causes septal perfusion defects in radionuclide myocardial perfusion imaging using exercise (Ex) but rarely using vasodilator stress. We studied whether this is due to an underlying structural disease inherent to spontaneous LBBB or whether it is also found in temporary LBBB induced by right ventricular pacing (PM) indicating a functional rather than a structural alteration. METHODS AND RESULTS Regional myocardial blood flow (MBF) at rest and at Ex was measured with 15O-H2O and PET in 10 age-matched healthy volunteers (controls), 10 LBBB patients and 10 PM patients with right ventricular pacing off and on (PM off and PM on). Although at Ex septal MBF tended to be higher in LBBB than in controls (3.04 +/- 1.18 vs. 2.27 +/- 0.72 mL/min/g; P = ns), the ratio septal/lateral MBF was 19% lower in LBBB than in controls (P < 0.05). Similarly, switching PM on at Ex decreased the ratio septal/lateral MBF by 17% (P < 0.005). CONCLUSION The apparent septal perfusion defect in LBBB is mainly due to a relative lateral hyperperfusion rather than to an absolute septal flow decrease. This pattern seems to be reversibly inducible by right ventricular pacing, suggesting a functional rather than a structural alteration.

Caffeine Impairs Myocardial Blood Flow Response to Physical Exercise in Patients with Coronary Artery Disease as well as in Age-Matched Controls

Background Caffeine is one of the most widely consumed pharmacologically active substances. Its acute effect on myocardial blood flow is widely unknown. Our aim was to assess the acute effect of caffeine in a dose corresponding to two cups of coffee on myocardial blood flow (MBF) in coronary artery disease (CAD). Methodology/Principal Findings MBF was measured with 15O-labelled H2O and Positron Emission Tomography (PET) at rest and after supine bicycle exercise in controls (n = 15, mean age 58±13 years) and in CAD patients (n = 15, mean age 61±9 years). In the latter, regional MBF was assessed in segments subtended by stenotic and remote coronary arteries. All measurements were repeated fifty minutes after oral caffeine ingestion (200 mg). Myocardial perfusion reserve (MPR) was calculated as ratio of MBF during bicycle stress divided by MBF at rest. Resting MBF was not affected by caffeine in both groups. Exercise-induced MBF response decreased significantly after caffeine in controls (2.26±0.56 vs. 2.02±0.56, P<0.005), remote (2.40±0.70 vs. 1.78±0.46, P<0.001) and in stenotic segments (1.90±0.41 vs. 1.38±0.30, P<0.001). Caffeine decreased MPR significantly by 14% in controls (P<0.05 vs. baseline). In CAD patients MPR decreased by 18% (P<0.05 vs. baseline) in remote and by 25% in stenotic segments (P<0.01 vs. baseline). Conclusions We conclude that caffeine impairs exercise-induced hyperaemic MBF response in patients with CAD to a greater degree than age-matched controls.

Role of attenuation correction to discriminate defects caused by left bundle branch block versus coronary stenosis in single photon emission computed tomography myocardial perfusion imaging.

Purpose: To define the impact of attenuation correction (AC) on interpretation of perfusion abnormalities induced by left bundle branch block (LBBB) in myocardial perfusion imaging (MPI) and single photon emission computed tomography (SPECT). Methods: Thirty-six patients with spontaneous and 12 with pacemaker (PM)-induced LBBB (mean age 68.6±9.7) underwent gated 1-day adenosine stress/rest Tc-99m tetrofosmin SPECT on a hybrid SPECT-CT dual-head detector camera with Hawkeye facility (Infinia, GE Healthcare, Milwaukee, WI). Images were analyzed using iterative reconstruction (IR) and AC by computerized tomography (IR-AC) and compared with filtered back protection (FBP) as a standard of reference. Defect extent and severity for the anterior, septal, apical, inferior, and lateral regions were assessed by computerized analysis. The combination of septal with anterior and/or apical perfusion defects was attributed to the typical LBBB-induced pattern. Results: LBBB caused a typical perfusion pattern in 24 patients with spontaneous and in 10 with PM-induced LBBB, whereas MPI was normal in 14 patients. FBP revealed a partial reversibility of anterior (spontaneous LBBB) and apical-septal (spontaneous and PM-induced LBBB) defect severity. By IR-AC, LBBB caused comparable anteroseptal reversible perfusion defects (P < 0.05) but fixed apical defects. Apical-septal defect severity was higher and defect extent was larger in IR-AC compared with FBP (both P < 0.05). Defect extent was unchanged between rest and stress for both reconstructions. Conclusions: Spontaneous and PM-induced LBBB often induces typical perfusion defects in MPI at stress, partly reversible at rest. With IR-AC this typical pattern is more pronounced and less reversible, strengthening the confidence to discriminate such findings from ischemia.

COMBINED ANGIOGRAPHY AND COMPUTED TOMOGRAPHY SYSTEM AS A NOVEL IMAGING MODALITY TO IMPROVE ANTEGRADE REVASCULARIZATION OF CHRONIC TOTAL OCCLUSIONS

For complete antegrade revascularization of a chronic total occlusion (CTO) intimal plaque tracking is crucial. However, by angiography the intimal plaque cannot be distinguished from the subintimal space and even the course of the occluded vessel is often unclear. The spatial resolution of computed

Recovery mismatch between myocardial blood flow and cardiac workload after physical exercise: a positron emission tomography study

AIMS We studied the interrelation between oxygen consumption and myocardial blood flow (MBF) during recovery. MBF is directly dependent on oxygen consumption. The latter is linearly related to the heart rate-blood pressure product (RPP, bpm × mmHg), an index reflecting external cardiac work. In the immediate post-exercise period, cardiac output decreases considerably. This is expected to be paralleled by a rapid fall in oxygen demand, rendering ischaemia unlikely. Thus, the phenomenon of ST-segment depression during recovery remains unexplained. METHODS AND RESULTS (15)O-labelled water and positron emission tomography were used to measure MBF in 14 young healthy volunteers (mean age 27 ± 3 years) during the following study conditions: (i) at rest, (ii) during a steady submaximal supine bicycle exercise stress within the scanner, and (iii) during recovery immediately after cessation of exercise. During recovery, RPP decreased by 43% (18 768 ± 1337 vs. 11 652 ± 3224, P < 0.001). In contrast, the associated decrease in MBF (2.52 ± 0.52 vs. 1.93 ± 0.50 mL/min/g, P < 0.001) and perfusion reserve (2.68 ± 0.51 vs. 2.03 ± 0.42, P < 0.001) was significantly less pronounced (-24%, P < 0.01), indicating a relative delay in MBF recovery compared with cardiac work load. CONCLUSION The mismatch between a rapid decrease in cardiac workload but preserved hyperaemic response early after cessation of physical exercise suggests an uncoupling of cardiac work and MBF during recovery.

Erratum: Tetrahydrobiopterin restores impaired coronary microvascular dysfunction in hypercholesterolaemia (European Journal of Nuclear Medicine and Molecular Imaging (2005) 32 (84-91) DOI: 10.1007/s00259-004-1621-y)

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.