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; mlmin−1g−1) was measured at rest, during adenosine-induced (140μgkg−1min−1 over 7min) 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 60min later, after intravenous infusion of BH4 (10mgkg−1 body weight over 30min). 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±0.58vs 3.41±0.73mlmin−1g−1, p<0.05) and hypercholesterolaemic subjects (2.47±0.78vs 2.70±0.72mlmin−1g−1, p<0.01) but had no influence on MBF at rest or during adenosine-induced hyperaemia in controls (4.52±1.10vs 4.85±0.45mlmin−1g−1, p=NS) or hypercholesterolaemic subjects (4.86±1.18vs 4.53±0.93mlmin−1g−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 hypercholesterolaemi

Influence of cardiac hemodynamic parameters on coronary artery opacification with 64-slice computed tomography

The purpose of this study was to evaluate the influence of ejection fraction (EF), stroke volume (SV), heart rate, and cardiac output (CO) on coronary artery opacification with 64-slice computed tomography (CT). Sixty patients underwent, retrospectively, electrocardiography-gated 64-slice CT coronary angiography. Left ventricular EF, SV, and CO were calculated with semi-automated software. Attenuation values were measured and contrast-to-noise ratios (CNRs) were calculated in the proximal right coronary artery (RCA) and left main artery (LMA). Mean EF during scanning was 61.5±12.4%, SV was 63.2±15.6ml, heart rate was 62.5±11.8beats per minute (bpm), and CO was 3.88±1.06l/min. There was no significant correlation between the EF and heart rate and the attenuation and CNR in either coronary artery. A significant negative correlation was found in both arteries between SV and attenuation (RCA r=−0.26, P<0.05; LMA r=−0.34, P<0.01) and between SV and CNR (RCA r=−0.26, P<0.05; LMA r=−0.26, P<0.05). Similarly, a significant negative correlation was found between the CO and attenuation (RCA r=−0.42, P<0.05; LMA r=−0.56, P<0.001) and between the CO and CNR (RCA r=−0.39, P<0.05; LMA r=−0.44, P<0.001). The actual hemodynamic status of the patient influences the coronary artery opacification with 64-slice CT, in that vessel opacification decreases as SV and CO increas

Effects of AV delay programming on ventricular resynchronisation: role of radionuclide ventriculography

Purpose: Optimal atrioventricular delay (AVD) setting for cardiac resynchronisation therapy, i.e. biventricular pacing in patients with heart failure, remains a formidable challenge. Thus, the purpose of this study was to evaluate the effects of different AVD on inter- and intra-ventricular resynchronisation using phase histograms of radionuclide ventriculography (RNV). Methods: In 17 consecutive patients (mean age 64 ± 6years), RNV was performed 236 ± 350days after pacemaker implantation for cardiac resynchronisation therapy. Images were acquired during atrial pacing at 80bpm and during biventricular pacing with AVD ranging from 80 to 160ms. Inter-ventricular dyssynchrony was measured by the delay between the mean phase angles of the left and right ventricles. Intra-ventricular dyssynchrony was measured by the standard deviation (SD) of left ventricular phase histograms. Results: Left ventricular (LV) ejection fraction (EF) was inversely correlated to LV dyssynchrony (SD of LV phase histogram, R = −0.82, p < 0.0001). However, the increase in LVEF by biventricular pacing (mean +4.4 ± 4%) showed only modest correlation to the resulting resynchronisation effect (characterised by a −13 ± 8° decrease in LV phase histogram SD, R = −0.38, p < 0.0001). Conclusion: RNV is helpful in optimising pacing parameters for resynchronisation therapy. Varying AVD did not have a major impact on intra- or inter-ventricular resynchronisation. Thus, the benefit of AVD-based LVEF optimisation seems to result from atrioventricular resynchronisatio

Coronary CT angiography and myocardial perfusion imaging to detect flow-limiting stenoses: a potential gatekeeper for coronary revascularization?

Aims To evaluate the diagnostic accuracy of a combined non-invasive assessment of coronary artery disease with coronary CT angiography (CTA) and myocardial perfusion imaging (MPI) for the detection of flow-limiting coronary stenoses and its potential as a gatekeeper for invasive examination and treatment. Methods and results In 78 patients (mean age 65 ± 9 years) referred for coronary angiography (CA), additional CTA and MPI (using single-photon emission-computed tomography) were performed and the findings not communicated. Detection of flow-limiting stenoses (justifying revascularization) by the combination of CTA and MPI (CTA/MPI) was compared with the combination of quantitative coronary angiography (QCA) plus MPI (QCA/MPI), which served as standard of reference. The findings of both combinations were related to the treatment strategy (revascularization vs. medical treatment) chosen in the catheterization laboratory based on the CA findings. Sensitivity, specificity, positive and negative predictive value, and accuracy of CTA/MPI for the detection of flow-limiting coronary stenoses were 100% each. More than half of revascularization procedures (21/40, 53%) was performed in patients without flow-limiting stenoses and 76% (47/62) of revascularized vessels were not associated with ischaemia on MPI. Conclusion The combined non-invasive approach CTA/MPI has an excellent accuracy to detect flow-limiting coronary stenoses compared with QCA/MPI and its use as a gatekeeper appears to make a substantial part of revascularization procedures redundan

Use of coronary calcium score scans from stand-alone multislice computed tomography for attenuation correction of myocardial perfusion SPECT

Purpose: To evaluate the use of CT attenuation maps, generated from coronary calcium scoring (CCS) scans at in- and expiration with a 64-slice CT scanner, for attenuation correction (AC) of myocardial perfusion SPECT images. Methods: Thirty-two consecutive patients underwent 99mTc-tetrofosmin gated adenosine stress/rest SPECT scan on an Infinia Hawkeye SPECT-CT device (GE Medical Systems) followed by CCS and CT angiography on a 64-slice CT. AC of the iteratively reconstructed images was performed with AC maps obtained: (a) from the "Hawkeye” low-resolution X-ray CT facility attached to the Infinia camera (IRAC); (b) from the CCS scan acquired on a 64-slice CT scanner during maximal inspiration (ACINSP) and (c) during normal expiration (ACEXP). Automatically determined uptake values of stress scans (QPS, Cedars Medical Sinai) from ACINSP and ACEXP were compared with IRAC. Agatston score (AS) values using ACINSPversus ACEXP were also compared. Results: ACINSP and ACEXP resulted in identical findings versus IRAC by visual analysis. A good correlation for uptake values between IRAC and ACINSP was found (apex, r=0.92; anterior, r=0.85; septal, r=0.91; lateral, r=0.86; inferior, r=0.90; all p<0.0001). The correlation was even closer between IRAC and ACEXP (apex, r=0.97; anterior, r=0.91; septal, r=0.94; lateral, r=0.92; inferior, r=0.97; all p<0.0001). The mean AS during inspiration (319±737) and expiration(317±778) was comparable (p=NS). Conclusion: Attenuation maps from CCS allow accurate AC of SPECT MPI images. ACEXP proved superior to ACINSP, suggesting that in hybrid scans CCS may be performed during normal expiration to allow its additional use for AC of SPECT MP

Coronary artery stent geometry and in-stent contrast attenuation with 64-slice computed tomography

We aimed at assessing stent geometry and in-stent contrast attenuation with 64-slice CT in patients with various coronary stents. Twenty-nine patients (mean age 60 ± 11years; 24 men) with 50 stents underwent CT within 2weeks after stent placement. Mean in-stent luminal diameter and reference vessel diameter proximal and distal to the stent were assessed with CT, and compared to quantitative coronary angiography (QCA). Stent length was also compared to the manufacturer's values. Images were reconstructed using a medium-smooth (B30f) and sharp (B46f) kernel. All 50 stents could be visualized with CT. Mean in-stent luminal diameter was systematically underestimated with CT compared to QCA (1.60 ± 0.39mm versus 2.49 ± 0.45mm; P < 0.0001), resulting in a modest correlation of QCA versus CT (r = 0.49; P < 0.0001). Stent length as given by the manufacturer was 18.2 ± 6.2mm, correlating well with CT (18.5 ± 5.7mm; r = 0.95; P < 0.0001) and QCA (17.4 ± 5.6mm; r = 0.87; P < 0.0001). Proximal and distal reference vessel diameters were similar with CT and QCA (P = 0.06 and P = 0.03). B46f kernel images showed higher image noise (P < 0.05) and lower in-stent CT attenuation values (P < 0.001) than images reconstructed with the B30f kernel. 64-slice CT allows measurement of coronary artery in-stent density, and significantly underestimates the true in-stent diameter compared to QC

Optimal image reconstruction intervals for non-invasive coronary angiography with 64-slice CT

The reconstruction intervals providing best image quality for non-invasive coronary angiography with 64-slice computed tomography (CT) were evaluated. Contrast-enhanced, retrospectively electrocardiography (ECG)-gated 64-slice CT coronary angiography was performed in 80 patients (47 male, 33 female; mean age 62.1±10.6years). Thirteen data sets were reconstructed in 5% increments from 20 to 80% of the R-R interval. Depending on the average heart rate during scanning, patients were grouped as <65bpm (n=49) and ≥65bpm (n=31). Two blinded and independent readers assessed the image quality of each coronary segment with a diameter ≥1.5mm using the following scores: 1, no motion artifacts; 2, minor artifacts; 3, moderate artifacts; 4, severe artifacts; and 5, not evaluative. The average heart rate was 63.3±13.1bpm (range 38-102). Acceptable image quality (scores 1-3) was achieved in 99.1% of all coronary segments (1,162/1,172; mean image quality score 1.55±0.77) in the best reconstruction interval. Best image quality was found at 60% and 65% of the R-R interval for all patients and for each heart rate subgroup, whereas motion artifacts occurred significantly more often (P<0.01) at other reconstruction intervals. At heart rates <65bpm, acceptable image quality was found in all coronary segments at 60%. At heart rates ≥65bpm, the whole coronary artery tree could be visualized with acceptable image quality in 87% (27/31) of the patients at 60%, while ten segments in four patients were rated as non-diagnostic (scores 4-5) at any reconstruction interval. In conclusion, 64-slice CT coronary angiography provides best overall image quality in mid-diastole. At heart rates <65bpm, diagnostic image quality of all coronary segments can be obtained at a single reconstruction interval of 60

Accuracy of 64-slice CT angiography for the detection of functionally relevant coronary stenoses as assessed with myocardial perfusion SPECT

Purpose: CT angiography (CTA) offers a valuable alternative for the diagnosis of CAD but its value in the detection of functionally relevant coronary stenoses remains uncertain. We prospectively compared the accuracy of 64-slice CTA with that of myocardial perfusion imaging (MPI) using 99mTc-tetrofosmin-SPECT as the gold standard for the detection of functionally relevant coronary artery disease (CAD). Methods: MPI and 64-slice CT were performed in 100 consecutive patients. CTA lesions were analysed quantitatively and area stenoses ≥50% and ≥75% were compared with the MPI findings. Results: In 23 patients, MPI perfusion defects were found (12 reversible, 13 fixed). A total of 399 coronary arteries and 1,386 segments was analysed. Eighty-four segments (6.1%) in 23 coronary arteries (5.8%) of nine patients (9.0%) were excluded owing to insufficient image quality. In the remaining 1,302 segments, quantitative CTA revealed stenoses ≥50% in 57 of 376 coronary arteries (15.2%) and stenoses ≥75% in 32 (8.5%) coronary arteries. Using a cut-off at ≥75% area stenosis, CTA yielded the following sensitivity, specificity, negative (NPV) and positive predictive value (PPV), and accuracy for the detection of any (fixed and reversible) MPI defect: by patient, 75%, 90%, 93%, 68% and 87%, respectively; by artery, 76%, 95%, 99%, 50% and 94%, respectively. Conclusion: Sixty-four-slice CTA is a reliable tool to rule out functionally relevant CAD in a non-selected population with an intermediate pretest likelihood of disease. However, an abnormal CTA is a poor predictor of ischaemi

Sense-B-noise: an enigmatic cause for inappropriate shocks in subcutaneous implantable cardioverter defibrillators.

AIMS Subcutaneous implantable cardioverter defibrillators (S-ICDs) are well established. However, inappropriate shocks (IAS) remain a source of concern since S-ICDs offer very limited troubleshooting options. In our multicentre case series, we describe several patients who experienced IAS due to a previously unknown S-ICD system issue. METHODS AND RESULTS We observed six patients suffering from this novel IAS entity. The IAS occurred exclusively in primary or alternate S-ICD sensing vector configuration (therefore called 'Sense-B-noise'). IAS were caused by non-physiologic oversensing episodes characterized by intermittent signal saturation, diminished QRS amplitudes, and disappearance of the artefacts after the IAS. Noise/oversensing could not be provoked by manipulation, X-ray did not show evidence for lead/header issues and impedance measurements were within normal limits. The pooled experience of our centres implies that up to ∼5% of S-ICDs may be affected. The underlying root cause was discussed extensively with the manufacturer but remains unknown and is under further investigation. CONCLUSION Sense-B-noise is a novel cause for IAS due to non-physiologic signal oversensing, arising from a previously unknown S-ICD system issue. Sense-B-noise may be suspected if episodes of signal saturation in primary or alternate vector configuration are present, oversensing cannot be provoked, and X-ray and electrical measurements appear normal. The issue can be resolved by reprogramming the device to secondary sensing vector

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 (15)O-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