Stenotic Pressure Research Articles

Abstract WP137: A CT Perfusion Based Computational Modeling for Improved Risk Stratification of Haemodynamically Significant ICAD

Aim: In endovascular ICAD treatment, an individualized patient-specific treatment pathway may be very helpful. Patient selection for endovascular treatment based on anatomical markers has not been shown to be effective in past clinical trials. This pilot study combines CT perfusion (CTP) analysis and computational fluid dynamics to identify hemodynamically significant patients for a reliable pathway for intervention planning. Methods: We assessed patients from two stroke centers with 50-99% ICAD lesions. Using a novel technique, CTP scans generated acute vascular territory maps for major cerebral arteries (ACA,MCA,PCA) with perfusion Time-to-peak (TTP) maps. Patient-specific blood flow simulations using physiology-informed boundary conditions calculated stenotic pressure ratios for both the patient’s acute and a population-based healthy scenario. The changes in affected territory volumes and pressure ratio between healthy and acute conditions and the acute TTP delays were presented to an expert reader who stratified cases into three clinical groups (A) non-hemodynamic, (B) hemodynamically hazardous with insufficient collateral support and (C) hemodynamically stable due to collateralisation. These results were compared against patient outcomes of recurrent ischemic events attributed to the target stenosis using the commonly used 70% threshold. Results: (95%CI in brackets) Patients (n=47, age: 73±11Y, 23F/24M) were stratified across the three categories A) 30, B) 15, C) 2. Of the patient groups with follow-up (n=31), categorisation of hemodynamic ICAD against recurrent ipsilateral stroke in territory (n=8) yielded a sensitivity of 75% [34-97] and specificity of 91% [72-98]. Mean±standard deviation of stenosis degree (SD) 55±14% for patients across each cohort was A) 50±11%, B) 70±9%, C) 70%. This is compared to using 70% stenosis threshold for dichotomising patients against risk of recurrent stroke, which yielded a sensitivity of 62.5% [24-91], and specificity of 87% [66-97]. Conclusions: We report on a CTP derived method for stratifying hemodynamically significant ICAD. The methodology has potential in both in assessing symptomatic chronic ICAD and identifying cohorts who would benefit from endovascular intervention.

Non-invasive MRI Derived Hemodynamic Simulation to Predict Successful vs. Unsuccessful Catheter Interventions for Branch Pulmonary Artery Stenosis: Proof-of-Concept and Experimental Validation in Swine.

This study assessed the ability of hemodynamic simulations to predict the success of catheter interventions in a swine model of branch pulmonary artery stenosis (bPAS). bPAS commonly occurs in congenital heart disease and is often managed with catheter based interventions. However, despite technical success, bPAS interventions do not lead to improved distal pulmonary blood flow (PBF) distribution in approximately 1/3rd of patients. New tools are needed to better identify which patients with bPAS would most benefit from catheter interventions. For 13 catheter intervention cases in swine with surgically created left PAS (LPAS), PA pressures from right heart catheterization (RHC) and PBF distributions from MRI were measured before and after catheter interventions. Hemodynamic simulations with a reduced order computational fluid dynamics (CFD) model were performed using non-invasive PBF measurements derived from MRI, and then correlated with changes in invasive measures of hemodynamics and PBF distributions before and after catheter intervention to relieve bPAS. Compared to experimentally measured changes in left PBF distribution, simulations had a small bias (3.4 ± 11.1%), moderate agreement (ICC = 0.69 [0.24-0.90], 0.71 [0.23-0.91]), and good diagnostic capability to predict successful interventions (> 20% PBF increase) (AUC 0.83 [0.59-1.0]). Simulations had poorer prediction of changes in stenotic pressure gradient (ICC = 0.28 [- 0.33 to 0.73], r = 0.57 [- 0.04 to 0.87]) and MPA systolic pressure (ICC = 0.00 [- 0.52 to 0.53], r = 0.29 [- 0.32 to 0.72]). While there was only weak to moderate agreement between predicted and measured changes in PA pressures and pulmonary blood flow distributions, hemodynamic simulations did show good diagnostic value for predicting successful versus unsuccessful catheter based interventions to relieve bPAS. The results of this proof of concept study are promising and should encourage future development for using hemodynamic models in planning interventions for patients with bPAS.

Importance of guiding catheter disengagement during measurement of fractional flow reserve in patients with an isolated proximal left anterior descending artery stenosis.

To determine the impact of ostial guiding catheter disengagement during measurement of fractional flow reserve (FFR) in patients with an isolated proximal left anterior descending artery (LAD) stenosis. Measurements of FFR were performed in 21 patients with an isolated intermediate lesion of the proximal LAD. Proximal aortic pressure (Pa), distal post stenotic pressure (Pd), and Pd/Pa were recorded at baseline, after at least 90 sec of intravenous (IV) adenosine infusion with the guiding catheter still engaged in the coronary ostium (Pa1 , Pd1 , FFReng ), and after at least 30 sec of guiding catheter disengagement back to the aorta (Pa2 , Pd2 , FFRdis ). The average value of Pd/Pa at baseline was 0.92 ± 0.04. After 110 ± 8 sec of IV adenosine infusion, FFReng was 0.81 ± 0.07, which decreased to 0.77 ± 0.08 (FFRdis ) after 38 ± 6 sec of guiding catheter disengagement. The mean ΔFFR (FFReng - FFRdis ) was 0.05 ± 0.04. As compared to baseline values, the mean change in FFR values was significantly increased after disengagement of the guiding catheter (Pd/Pabaseline - FFRdis vs. Pd/Pabaseline - FFReng , 0.15 ± 0.05 vs. 0.10 ± 0.04, P < 0.0001). Before guiding catheter disengagement, eight patients (38%) had an FFR value ≤ 0.8. Following disengagement of the guiding catheter, the new FFR values decreased below 0.8 in six additional patients (28%), with subsequent change in treatment strategy. During FFR assessment of isolated intermediate proximal LAD lesions, guiding catheter disengagement is associated with a decrease in mean FFR values. In patients with FFR values lying close to the treatment threshold, this can have an impact on treatment strategy.

Detection of peripheral vascular stenosis by assessing skeletal muscle flow reserve

We sought to determine whether the severity of peripheral arterial disease (PAD) can be assessed by measuring blood flow reserve in limb skeletal muscle with contrast-enhanced ultrasound (CEU). Noninvasive imaging of distal limb perfusion could improve management of patients with PAD by evaluating the impact of large and small vessel disease, and collateral flow. In 12 dogs, blood flow in the quadriceps femoris was measured by CEU at rest and during either electrostimulated contractile exercise or adenosine infusion. Femoral artery blood flow was measured by Doppler ultrasound. Studies were performed in the absence and presence of either moderate or severe stenosis (pressure gradient of 10 to 20 mm Hg and >20 mm Hg, respectively). Resting femoral artery blood flow progressively decreased with stenosis severity, while resting skeletal muscle flow was reduced only with severe stenosis (52 +/- 21% of baseline, p < 0.05), indicating the presence of collateral flow. Skeletal muscle flow reserve during contractile exercise or adenosine decreased incrementally with increasing stenosis severity (p < 0.01). The stenotic pressure gradient correlated with skeletal muscle flow reserve for exercise and adenosine (r = 0.70 for both, p < 0.01). Contrast-enhanced ultrasound of limb skeletal muscle can be used to assess the severity of PAD by measuring muscle flow reserve during either contractile exercise or pharmacologic vasodilation. Unlike currently used methods, this technique may provide a measure of the physiologic effects of large- and small-vessel PAD, and the influence of collateral perfusion.

The Order of Dilator-Constrictor Administration Affects Stenotic Hemodynamic Responses

This study tested the hypothesis that, due to intraluminal pressure changes, the order of constrictor-dilator administration alters stenotic hemodynamic responses. Canine carotid arteries were perfused with a physiologic salt solution under constant pressure (100 mm Hg). An intraluminal stenosis partially obstructed the arteries. Pressures proximal and distal to the artery and the flow were continually recorded as norepinephrine (10(-9)-10(-6) M) was added to the perfusate. Adding diltiazem (10(-7) M) before norepinephrine shifted the effective half maximum dose (ED50) of the norepinephrine flow curve from 7.35 +/- 0.66 X 10(-8) M to 6.39 +/- 0.72 X 10(-7) M (p < 0.05). More important, adding 10(-7) M diltiazem after norepinephrine-induced constriction did not reestablish stenotic pressure or flow: A 30-fold increase in diltiazem concentration (3.16 X 10(-6)M) was required to reestablish stenotic pressure (62.6 +/- 4.4 mm Hg) and flow (25.4 +/- 3.2 ml/min). Similarly, adding nitroglycerin (10(-7) M) before norepinephrine shifted the ED50 from 7.21 +/- 0.58 X 10(-8) to 5.94 +/- 0.78 X 10(-6) (p < 0.05). Adding 10(-7) M nitroglycerin after norepinephrine did not reestablish stenotic pressure or flow: 3.16 X 10(-6) M nitroglycerin was required to reestablish stenotic pressure (59.2 +/- 4.8 mm Hg) and flow (23.2 +/- 2.7 mL/min). This constrictor-dilation history did not occur in isolated arterial rings (norepinephrine + nitroglycerin = 38.1 +/- 13.9 g/cm2; nitroglycerin + norepinephrine = 42.2 +/- 9.4 g/cm2; p = not significant [NS]) or in normal arteries (norepinephrine + nitroglycerin = 4.89 +/- 0.14 mm [external diameter]; nitroglycerin + norepinephrine = 4.92 +/- 0.23 mm; p = NS). In stenotic arteries, intraluminal pressure influenced the order of constrictor-dilator administration on hemodynamic response, which was not observed in isolated arterial rings or in normal arteries. This pressure-dependent sensitivity affects vasomotor tone and may be important in the pathophysiology of ischemia.

New concepts regarding constriction within a stenosis: Influence of intraluminal pressure changes

Morphologic and clinical studies clearly show that most human coronary lesions exhibit vasomotion. Variable ischemic thresholds, ischemia unrelated to workload, and variant angina further prove the presence of vasoconstriction in coronary artery disease. While vasoconstriction is important in the presentation of coronary artery disease, the unique type of contraction present in an arterial stenosis has been only recently examined. In normal large conduit arteries, the afterload opposing smooth muscle contraction is the intraluminal pressure, which remains relatively constant. In stenotic arteries, as the artery constricts, the pressure (or afterload) opposing smooth muscle shortening decreases, leading to exaggerated constriction and augmented arterial narrowing. Physiologically, this implies that a unique type of contraction (“heterotonic”) occurs within an arterial stenosis. Clinically, this type of contraction might explain the exaggerated shortening observed within an arterial stenosis. It also suggests that stenotic pressure is an important variable in the pathophysiology and potential treatment of angina pectoris.

Importance of intraluminal pressure on hemodynamics and vasoconstriction responses of stenotic arteries.

Clinical and morphological studies clearly indicate that most human coronary artery stenoses are capable of vasomotion. Variable ischemic thresholds, ischemia unrelated to work load, and variant angina further show the presence and importance of vasoconstriction in coronary artery stenosis. Despite the importance of vasoconstriction, the effect of intraluminal pressure on the hemodynamic response to vasoconstrictors has not yet been examined. Intraluminal pressure is a primary determinant of vessel size and the force opposing vasoconstriction. Accordingly, we examined the effects of intraluminal pressure on the hemodynamic response to norepinephrine (NE)-induced vasoconstriction. In canine carotid arteries perfused with physiological salt solution, pressures at the proximal and distal ends of the artery, as well as flow, were continuously recorded. We altered intraluminal pressure using three diverse interventions: changes in perfusion pressure, decreasing distal resistance, and collaterals. In normal, nonstenotic arteries, NE decreased the external vessel diameter but did not reduce flow. Perfusion pressure changes did not affect the ED50 of the NE-diameter relation. After an intraluminal stenosis was created, NE-induced constriction decreased flow. The threshold concentration of NE needed to decrease flow decreased as the perfusion pressure decreased (38.5 +/- 17.9, 2.3 +/- 1.3, and 0.12 +/- 0.1 x 10(-7) mol/l for 125, 100, and 75 mm Hg of perfusion pressure, respectively; p less than 0.05). Lowering distal resistance decreased stenotic pressure and decreased the threshold NE concentration from 5.4 +/- 1.9 to 0.34 +/- 0.2 x 10(-7) mol/l (p less than 0.05), and increasing stenotic pressure with collaterals increased the threshold NE concentration from 2.6 +/- 1.4 to 7.5 +/- 4.6 x 10(-7) mol/l (p less than 0.05). In stenotic arteries, interventions that lowered the intraluminal pressure decreased the threshold NE concentration needed to decrease flow, and interventions that raised the intraluminal pressure increased the threshold NE concentration. This pressure-dependent constrictor sensitivity affects the vasomotor tone and is important in pathophysiology of ischemia occurring with hypotension (low perfusion pressure) or mild increase in myocardial oxygen demand (low distal arteriolar resistance). The results also suggest that collaterals, by maintaining stenotic pressure, could decrease the constrictor sensitivity and prevent ischemia.

Impact of intraoperative echocardiography on surgical management of congenital heart disease

Intraoperative echocardiography was performed by epicardial, 2-dimensional, low- and high-pulsed repetition frequency, continuous-wave Doppler and color flow mapping in 50 patients. Forty studies were performed before and 44 studies after cardiopulmonary bypass. Studies before cardiopulmonary bypass agreed with preoperative evaluation. After cardio-pulmonary bypass, studies revealed that 11 of 25 patients who underwent repair of ventricular septal defects had residual ventricular septal defects, and 1 of 25 patients who underwent atrial septa) repair had 1 residual atria) communication. One patient with a “Swiss cheese” ventricular septum underwent repeat cardiopulmonary bypass to close residual ventricular septal defects. The patient with a residual atrial communication required immediate reoperation because of a right to left shunt after a modified Fontan procedure. Eight of 10 remaining residual ventricular septa) defects spontaneously closed 1 to 41 days after operation. Assessment of postcardiopulmonary bypass and postoperative valvular regurgitation in 21 valves revealed good correlation (p <0.01). However, 1 patient required reoperation for mitral valve replacement on the sixth postoperative day. The correlation was fair between postcardiopulmonary bypass and postoperative residual stenotic pressure gradients in 12 surgically repaired stenotic lesions. This study shows that little additional information is added to a comprehensive preoperative evaluation by precardiopulmonary bypass intraoperative echocardiography. Postcardiopulmonary bypass intraoperative echocardiography is useful identifying residual shunts. Assessment of stenotic gradients and valvular regurgitation must be interpreted in light of a changing hemodynamic state.

Stenotic amplification of vasoconstriction responses.

Based on simple hemodynamic principles, arterial stenoses could accentuate the effects of arterial vasoconstriction by reducing intraluminal pressure. To examine this mechanism we employed an in vitro stenotic carotid artery preparation. Eight carotid arteries, obtained from anesthetized heartworm-positive dogs, were isolated and perfused with a physiological salt solution under constant pressure (100 mmHg) and with a fixed distal resistance. After creating an intraluminal stenosis, proximal pressure, distal pressure, and flow were continuously recorded as norepinephrine was incrementally added to the perfusion reservoir. At each norepinephrine concentration, arterial dimensions were recorded on 35-mm film and measured by quantitative dimensional analysis. These data were approximated by a four-parameter logistic equation. The proximal diameter data were considered to represent solely the effects of arterial vasoconstriction, while the stenotic diameter data were considered to be affected both by arterial vasoconstriction and by stenotic pressures. The stenotic diameters shortened significantly more than the proximal diameter (1.2 +/- 2 vs. 0.5 +/- 0.1 mm, P less than 0.01). The shape of the stenotic diameter dose-response curve was similar to the distal pressure curve and was significantly (P less than 0.05; - 3.4 +/- 0.7) steeper than the proximal diameter curve (-0.7 +/- 0.1). Furthermore, the half maximum effective doses (ED50) were significantly interrelated for distal pressure and stenotic diameter data and unrelated for proximal diameter data. In five additional experiments, to eliminate the stenotic pressure changes, the flow was maintained constant. Maintaining stenotic vasoconstriction response (0.6 +/- 2 mm). The results of the present study show exaggerated stenotic vasoconstriction caused by a stenotic pressure decrease.(ABSTRACT TRUNCATED AT 250 WORDS)

Doppler Echocardiographic Quantification of Stenotic Valvular Lesions

SummaryThe individual performing quantitative measurements of valve stenosis must always be vigilant of the most common errors made in assessing stenotic lesions:1. Underestimation of pressure gradients across stenotic valves can lead to false‐negative diagnoses. A Doppler angle greater than 25 degrees or the failure to insonate the high‐velocity region are common causes.2. Over‐ and underestimation of pressure gradients is possible when angle correction is used.3. Mistaken sample volume position (such as detection of high‐velocity mitral regurgitation when assessing aortic stenosis) can lead to overestimation of stenotic pressure gradients.4. Improper instrument settings can lead to inaccurate velocity measurements.We have entered an area in which Doppler and imaging echocardiography are capable of producing accurate hemodynamic data on patients with stenotic valve lesions. Such data can be used to make surgical decisions or to avoid further, sometimes more definitive, diagnostic tests. We must use care to assure that the measurements that we report are appropriate and accurate. It is appropriate to integrate the Doppler and imaging echocardiographic data with information obtained from history, physical exam, ECG, and chest roentgenogram to provide the most accurate assessment of the severity of the valve lesion(s). It is also important to interpret the quality of a study and report the likelihood that the study is complete and the results are highly accurate or that the study was difficult and may be incomplete.

Mechanism for dynamic changes in stenotic severity.

The mechanism responsible for rapid changes in stenotic severity or resistance due to alterations in perfusion pressure and distal resistance is addressed by this study. An in vitro, eccentric arterial stenosis model was created using 15 canine carotid arteries cannulated with silicone plugs containing special pressure-transducing catheters designed to measure pressure directly, within the stenosis. The vessels were perfused at perfusion pressures of 150, 100, and 75 mmHg and at two levels of distal resistance while perfusion pressure, distal pressure, stenotic pressure, and flow were recorded. Orthogonal arteriograms were performed. Stenotic resistance was calculated as (perfusion pressure--distal pressure)/flow. All variables changed significantly (P less than 0.05) with decreases in perfusion pressure. Stenotic resistance always increased (P less than 0.02) as perfusion pressure or distal resistance decreased. These dynamic changes in stenotic resistance occurred at stenotic pressures well above the atmospheric, extraluminal pressure. Arteriographic data demonstrated decreasing stenotic luminal area with decreasing stenotic pressure. These results confirm the assertion that rapid changes in stenotic resistance are related to changes in stenotic luminal area and are not due to extrinsic forces. The principles of the Starling resistor are, therefore, not applicable to dynamic arterial stenoses. This information is immediately relevant to clinical situations in which complaint, severe stenosis results in ischemia.