Remineralization of lytic spinal metastases after radiotherapy

BACKGROUND CONTEXT: Palliative radiotherapy (RT) can lead to remineralization of osteolytic lesions thereby potentially restoring some of the weight-bearing capacity and preventing vertebral collapse. It is not clear, however, under which circumstances remineralization of osteolytic lesions occurs. PURPOSE: The aim of this study was to investigate the change in bone mineral density in spinal metastases after RT compared to a reference region, and find associated factors. STUDY DESIGN: Retrospective analysis within prospective observational cohort OUTCOME MEASURES: change in bone mineral density measured in Hounsfield Units (HU). PATIENT SAMPLE: patients treated with RT for (painful) bone metastases. METHODS: Patients with spinal metastases were included if computed tomography scans both pre- and post-RT were available. Bone density was measured in HU. A region of interest (ROI) was drawn manually in the metastatic lesion. As a reference, a measurement of bone density in adjacent, unaffected, and non-irradiated vertebrae was used. Factors tested for association were origin of the primary tumor, RT dose and fractionation scheme, and concomitant use of bisphosphonates. RESULTS: A total of 31 patients with 49 spinal metastases, originating from various primary tumors, were included. The median age on baseline was 58 years (IQR: 53–63) and median time between baseline and follow-up scan was 8.2 months (IQR: 3.0–18.4). Difference in HU in the lesion before and after treatment was 146.9 HU (95% CI 68.4–225.4; p<.01). Difference in HU in the reference vertebra between baseline and first follow-up was 19.1 HU (95% CI -47.9 to 86.0; p=.58). Difference between reference vertebrae and metastatic lesions on baseline was -194.1 HU (95% CI -276.2 to -112.0; p<.01). After RT, this difference was reduced to -50.3 HU (95% CI -199.6 to 99.0; p=.52). Patients using bisphosphonates showed a greater increase in HU, 194.1 HU versus 60.6 HU, p=.01. CONCLUSIONS: Palliative radiation of osteolytic lytic spinal metastases is positively associated with an increased bone mineral density at follow-up. The use of bisphosphonates was linked to an increased bone mineral density when used during or after RT

Increased diastolic time fraction as beneficial adjunct of alpha(1)-adrenergic receptor blockade after percutaneous coronary intervention

Kolyva C, Verhoeff BJ, Spaan JA, Piek JJ, Siebes M. Increased diastolic time fraction as beneficial adjunct of alpha(1)-adrenergic receptor blockade after percutaneous coronary intervention. Am J Physiol Heart Circ Physiol 295: H2054-H2060, 2008. First published September 12, 2008; doi: 10.1152/ajpheart.91400.2007.-The effect of alpha(1)- receptor blockade with urapidil on coronary blood flow and left ventricular function has been attributed to relief of diffuse coronary vasoconstriction following percutaneous coronary intervention (PCI). We hypothesized that an increase in diastolic time fraction (DTF) contributes to the beneficial action of urapidil. In eleven patients with a 63% (SD 13) diameter stenosis, ECG, aortic pressure (P-a) and distal intracoronary pressure (P-d), and blood flow velocity were recorded at baseline and throughout adenosine-induced hyperemia. Measurements were obtained before and after PCI and after subsequent alpha(1)-receptor blockade with urapidil (10 mg ic). DTF was determined from the ECG and the P-a waveform. Functional parameters such as coronary flow velocity reserve, fractional flow reserve, and an index of hyperemic microvascular resistance (HMR) were assessed. Urapidil administration after PCI induced an upward shift in the DTF-heart rate relationship, resulting in a 3.1% (SD 2.7) increase in hyperemic DTF at a constant heart rate (P <0.005) due to a shorter duration of systole. Hyperemic P-a and P-d decreased, respectively, by 6.1% (SD 6.6; P <0.05) and 5.7% (SD 5.8; P <0.01) after alpha(1)- blockade. Although epicardially measured functional parameters were on average not altered by alpha(1)-blockade due to concurrent changes in pressure and heart rate, HMR decreased by urapidil in those patients where coronary pressure remained constant. In conclusion, alpha(1)-receptor blockade after PCI produced a modest but significant prolongation of DTF at a given heart rate, thereby providing an adjunctive beneficial mechanism for improving subendocardial perfusion, which critically depends on DT

Influence of increased heart rate and aortic pressure on resting indices of functional coronary stenosis severity

Baseline assessment of functional stenosis severity has been proposed as a practical alternative to hyperemic indices. However, intact autoregulation mechanisms may affect intracoronary hemodynamics. The aim of this study was to investigate the effect of changes in aortic pressure (Pa) and heart rate (HR) on baseline coronary hemodynamics and functional stenosis assessment. In 15 patients (55 +/- 3% diameter stenosis) Pa, intracoronary pressure (Pd) and flow velocity were obtained at control, and during atrial pacing at 120 bpm, increased Pa (+ 30 mmHg) with intravenous phenylephrine (PE), and elevated Pa while pacing at sinus heart rate (PE + sHR). We derived rate pressure product (RPP = systolic Pa 9 HR), baseline microvascular resistance (BMR = Pd/velocity), and stenosis resistance [BSR = (Pa - Pd)/velocity] as well as whole-cycle Pd/Pa. Tachycardia (120 +/- 1 bpm) raised RPP by 74% vs. control. Accordingly, BMR decreased by 27% (p <0.01) and velocity increased by 36% (p <0.05), while Pd/Pa decreased by 0.05 +/- 0.02 (p <0.05) and BSR remained similar to control. Raising Pa to 121 +/- 3 mmHg (PE) with concomitant reflex bradycardia increased BMR by 26% (p <0.001) at essentially unchanged RPP and velocity. Consequently, BSR and Pd/Pa were only marginally affected. During PE ? sHR, velocity increased by 21% (p <0.01) attributable to a 46% higher RPP (p <0.001). However, BMR, BSR, and Pd/Pa remained statistically unaffected. Nonetheless, the interventions tended to increase functional stenosis severity, causing Pd/Pa and BSR of borderline lesions to cross the diagnostic threshold. In conclusion, coronary microvascular adaptation to physiological conditions affecting metabolic demand at rest influences intracoronary hemodynamics, which may lead to altered basal stenosis indices used for clinical decision-makin

Minimal effect of collateral flow on coronary microvascular resistance in the presence of intermediate and noncritical coronary stenoses

Verhoeff B, van de Hoef TP, Spaan JA, Piek JJ, Siebes M. Minimal effect of collateral flow on coronary microvascular resistance in the presence of intermediate and noncritical coronary stenoses. Am J Physiol Heart Circ Physiol 303: H422-H428, 2012. First published June 22, 2012; doi: 10.1152/ajpheart.00003.2012.-Depending on stenosis severity, collateral flow can be a confounding factor in the determination of coronary hyperemic microvascular resistance (HMR). Under certain assumptions, the calculation of HMR can be corrected for collateral flow by incorporating the wedge pressure (P-w) in the calculation. However, although P-w > 25 mmHg is indicative of collateral flow, P-w does in part also reflect myocardial wall stress neglected in the assumptions. Therefore, the aim of this study was to establish whether adjusting HMR by P-w is pertinent for a diagnostically relevant range of stenosis severities as expressed by fractional flow reserve (FFR). Accordingly, intracoronary pressure and Doppler flow velocity were measured a total of 95 times in 29 patients distal to a coronary stenosis before and after stepwise percutaneous coronary intervention. HMR was calculated without (HMR) and with P-w-based adjustment for collateral flow (HMRC). FFR ranged from 0.3 to 1. HMR varied between 1 and 5 and HMRC between 0.5 and 4.2 mmHg.cm(-1).s. HMR was about 37% higher than HMRC for stenoses with FFR 0.8, the relative difference was reduced to 4.4 +/- 3.4%. In the diagnostically relevant range of FFR between 0.6 and 0.8, this difference was 16.5 +/- 10.4%. In conclusion, P-w-based adjustment likely overestimates the effect of potential collateral flow and is not needed for the assessment of coronary HMR in the presence of a flow-limiting stenosis characterized by FFR between 0.6 and 0.8 or for nonsignificant lesion

Single-wire pressure and flow velocity measurement to quantify coronary stenosis hemodynamics and effects of percutaneous interventions

Background - Lack of high-fidelity simultaneous measurements of pressure and flow velocity distal to a coronary artery stenosis has hampered the study of stenosis pressure drop - velocity (DeltaP-v) relationships in patients. Methods and Results - A novel 0.014-inch dual-sensor ( pressure and Doppler velocity) guidewire was used in 15 coronary lesions to obtain per-beat averages of pressure drop and velocity after an intracoronary bolus of adenosine. DeltaP-v relations from resting to maximal hyperemic velocity were constructed before and after stepwise executed percutaneous coronary intervention (PCI). Before PCI, half of the DeltaP-v relations revealed the presence of a compliant stenosis, which was stabilized by angioplasty. Fractional flow reserve (FFR), coronary flow reserve (CFVR), and velocity-based indices of stenosis resistance (h-SRv) and microvascular resistance (h-MRv) at maximal hyperemia were compared. Stepwise PCI significantly lowered h-SRv, with an initial marked reduction in hyperemic pressure drop followed by further gains in velocity. A concomitant significant reduction of h-MRv accounted for half of the gain in velocity after PCI. The average magnitude of absolute incremental hemodynamic changes was highest for h-SRv ( 56.8 +/- 39.2%) compared with CFVR (35.3 +/- 34.5%, P <0.005) or FFR (19.5 +/- 25.2%, P <0.0001). Conclusions - DeltaP-v relations comprehensively visualize improvements in coronary hemodynamics after PCI. h-SRv is a powerful and sensitive descriptor of the functional gain achieved by PCI, combining information about both pressure gradient and velocity, which are oppositely affected by PCI. Simultaneous assessment of stenosis and microvascular resistance may provide a valuable tool for guidance of PC

Influence of percutaneous coronary intervention on coronary microvascular resistance index

Background - Coronary microvascular resistance during maximal hyperemia is generally assumed to be unaffected by percutaneous coronary interventions (PCIs). We assessed a velocity-based index of hyperemic microvascular resistance (h-MRv) by using prototypes of a novel, dual-sensor (Doppler velocity and pressure) - equipped guidewire before and after PCI to test this hypothesis. Methods and Results - Aortic pressure, flow velocity (h-v), and pressure (h-P-d) distal to 24 coronary lesions were measured simultaneously during maximal hyperemia induced by intracoronary adenosine. Measurements were obtained in the reference vessel before PCI and in the target vessel before and after PCI, stenting, and ultrasound-guided, upsized stenting. h-P-d increased from 57.9+/-17.0 to 85.5+/-15.6 mm Hg, and h-MRv (ie, h-P-d/h-v) decreased from 2.74+/-1.40 to 1.58+/-0.61 mm Hg . cm(-1) . s after stenting (both P <0.001). The reduction in h-MRv accounted for 34% of the decrease in total coronary resistance achieved by PCI. h-MRv of the target vessel after PCI was lower than that of the corresponding reference vessel despite a higher h-P-d in the reference vessel (P <0.01). Post-PCI baseline MRv was correlated with baseline P-d before PCI (P <0.01). Conclusions - PCI-induced restoration of Pd resulted in a reduction of h-MRv in accordance with the pressure dependence of h-MRv. The decrease in h-MRv to a level below that of the corresponding reference vessel in the immediate post-PCI period and a lowered baseline MRv suggest microvascular remodeling induced by long-term exposure to a low-pressure environmen