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Biomedical subjects

K R Karsch

Publications and source records attributed to K R Karsch.

At least 73 records · Page 4Linked to original sources

Perspectives of coronary excimer laser angioplasty: multiplexing, saline flushing, and acoustic ablation control.

BACKGROUND AND OBJECTIVE: Bubble formation, pressure wave generation, and cavitations constitute major factors influencing the outcome of clinical Excimer laser angioplasty. Thus, the rationale of this study was to determine the extent of pressure waves occurring during excimer laser ablation and to discuss possibilities that allow a less traumatic plaque removal in the coronary circulation. STUDY DESIGN/MATERIALS AND METHODS: Conventional and experimental Xenon-Chlorid-Excimer lasers emitting light at a wave-length of 308 nm and a pulse duration of 115 ns were used for testing of signals. Whereas the conventional excimer laser light source transmits light through all fibers of a 1.7 mm laser catheter simultaneously, the prototype excimer laser divides the laser beam into several areas of uniform energy fluence by scanning the beam from one section to the other using the intermission between two laser discharges. Hydrophones consisting of piezoelectric films detected the acoustic signals, which were obtained on normal arterial wall and atherosclerotic plaque. RESULTS: Multiplexing decreases maximum pressures for both normal arterial wall and calcified plaque significantly, whereas pressure rise time remains comparable. During ablation of pure blood, a linear increase of peak pressures of 1 MPa at 10 mJ/mm2 to 7.5 MPa at 50 mJ/mm2 is found. Contrast media intensifies the extent of pressure wave formation. At 20 mJ/mm2, 60% contrast media added to blood results in an increase of maximum pressures from 1.5 MPa up to 5 MPa. Dilution with saline solution is effective; however, high concentrations of > 90% are required to achieve a significant pressure wave reduction. CONCLUSION: Peak pressures of several thousand kPa occur during excimer laser ablation of contrast media, blood, calcified plaque, and normal arterial wall in a decreasing order. Multiplexing and saline flushing are capable of reducing the intensity of the generated acoustic signals during tissue ablation. It has to be taken into consideration, however, that high concentrations of saline solution are necessary to achieve a significant reduction of peak pressures.

Acoustics↗

Time course of smooth muscle cell proliferation after local drug delivery of low-molecular-weight heparin using a porous balloon catheter.

It has been reported previously that systemic application of low molecular weight heparin (LMWH) suppresses smooth muscle cell (SMC) proliferation after balloon angioplasty in experimental studies. However, the high concentration of heparin required for a beneficial effect may cause severe bleeding complications. The ideal situation to overcome the systemic side effects would be to administer LMWH locally and deep into the arterial wall, which became possible by the development of porous balloon catheters. The in vivo feasibility of local delivery of LMWH using the porous balloon has been assessed by delivering tritium-marked LMWH into rabbit carotid arteries. The efficacy of the system was investigated by using a second injury animal model. After development of an intimal plaque by electrical stimulation, 61 rabbits were treated with the porous balloon after balloon angioplasty. In 23 rabbits, local drug delivery was accomplished with a porous balloon catheter (35 holes, hole diameter 75 microns, 2.5 mm catheter diameter). LMWH was locally administered with 4 ml (solution 375 anti-Xa-units/ml) and 2 atm. To study the extent of restenosis and morphological changes, these animals were killed 3, 7, 14, 28, or 56 d after intervention. After staining (hematoxylin, van Gieson, BrdU, RAM 11, alpha-actin) procedures to quantify SMC proliferation, intimal macrophages and morphological analysis were performed. Porous balloon treatment led to an increase in intimal SMC proliferation rate in the early stage after intervention. However, during the following time period, a significant decrease of the proliferation rate as compared with the animals treated with balloon angioplasty alone could be observed, which resulted in an only moderate increase of the intimal layer after local drug delivery compared with balloon angioplasty alone.

Angioplasty, Balloon↗

Efficacy of low-molecular-weight heparin delivery with the Dispatch catheter following balloon angioplasty in the rabbit iliac artery.

Local drug delivery can be achieved with active injection systems or passive contact of a compound with the arterial wall. The Dispatch catheter allows for passive diffusion of drugs from drug compartments while preserving blood flow through the central conduit. The aim of this study was to investigate whether a reduction in neointima formation can be achieved by local delivery of a limited amount of a highly concentrated solution of the low-molecular-weight heparin Reviparin. In 16 New Zealand white rabbits, successful balloon dilatation was performed in both iliac arteries, followed by local delivery of 4 ml Reviparin (1,000 IU/ml). The arteries were harvested at 7, 28, or 56 d following the procedure. The intimal cell layers increased substantially between 7 and 28 d following balloon dilatation with or without local drug delivery. The medial cell layers showed only a little increase. Proliferation of smooth muscle cells reached an early peak after 7 d, with a significantly higher proliferation index following local delivery. The maximum amount of macrophages in the intima and media was detected after 28 d. The lumen area decreased with time and was 0.6 +/- 0.7 mm2 in the local delivery group at 56 d compared with 0.5 +/- 0.5 mm2 in the control group. In conclusion, local delivery of Reviparin with the Dispatch catheter is safe and feasible. However, the infusion of highly concentrated low-molecular-weight heparin over a short period of time did not result in a reduction of neointima formation and restenosis following balloon dilatation in the rabbit iliac artery.

Angioplasty, Balloon, Coronary↗

Local drug delivery with porous balloons in the rabbit: assessment of vascular injury for an improvement of application parameters.

OBJECTIVES: Sufficient intramural drug concentrations with the use of porous balloon catheters can be achieved with additional vascular trauma only. However, effective delivery of a potent drug even in deeper layers of the vessel wall might outweigh these traumatic side effects. Given the porous balloon catheter, the parameters of injection pressure and applied fluid volume will influence the interventional result. METHODS: We tested a 2.5-mm porous balloon (35 75-micron pores) in the right carotid artery of New Zealand rabbits and used injection pressures of 1, 2, and 5 atm and fluid volumes of 2 and 4 ml of low-molecular-weight heparin solution in combination with the different parameters (n = 5 animals/group). In 50 rabbits, an intimal fibromuscular plaque was induced by using the electrostimulation model. Balloon dilatation and then application of the porous balloon was performed in 30 animals, 10 animals were only electrostimulated, and 10 animals served as a control group with balloon dilatation only. The vessels were excised 7 d after intervention, stained, and analyzed histomorpologically. Anti-Xa assays revealed the extent of systemically escaped drug, and serial cuts allowed for exact determination of vessel wall injuries. RESULTS: Effective local drug delivery could not be achieved with an injection pressure of less than 2 atm. Specific pressure-driven effects such as jet injuries could be identified. When the pressure was high enough for disruptive drug delivery (> or = 2 atm), fluid volumes of 4 ml led to loose elastic membranes and local thickening within the media. CONCLUSIONS: Sufficient intramural drug distribution using porous balloon catheters can be achieved with low injection pressures. Different fluid volumes strongly determine the extent of additional vascular injury.

Angioplasty, Balloon, Coronary↗

Growth factor expression of human arterial smooth muscle cells and endothelial cells in a transfilter coculture system.

By releasing growth factors, vascular cells can modulate proliferation and migration of neighboring cells in the arterial wall. Previous histological studies in transfilter cocultures, a culture model aimed to simulate vessel wall architecture, indicated that human arterial endothelial cells (haEC) can influence human arterial smooth muscle cell (haSMC) growth significantly. The aim of this study was to investigate the expression and secretion of various growth factors in order to better define the functional interactions between haEC and haSMC. Protein levels of platelet-derived-growth factor-AB (PDGF-AB), transforming-growth factor-beta1 (TGF-beta1), and tumor-necrosis factor-alpha (TNF-alpha) in mono- and cocultures were determined by ELISA 6, 12, 24, 48, 72 h after serum reduction. Highest PDGF-AB levels were found in monocultures with proliferative haEC, showing a peak after 24 h. In cocultures of haEC and haSMC, PDGF-AB levels were significantly lower. In contrast, neither proliferative, nor confluent haSMC released PDGF-AB significantly. Highest TGF-beta1 concentrations were detected in cocultures, followed by monocultures of haSMC and monocultures of haEC. In all cultures, TGF-beta1 levels increased in parallel with cultivation time and cell numbers, showing a maximum after 72 h. TNF-alpha could not be detected in any culture. Northern blots demonstrated a strong expression of PDGF-B chain-mRNA in haEC, but not in haSMC. PDGF-A chain and TGF-beta1-mRNA were expressed by haSMC and haEC. Addition of PDGF-AB to haSMC resulted in a potent growth stimulation, whereas TGF-beta1 and TNF-alpha exerted only moderate, divergent effects on haSMC. Histological observations in transfilter cocultures demonstrated that proliferative haEC induce the formation of fibromuscular plaques. These results suggest that proliferative haEC act as potent growth stimulators for haSMC, predominantly by PDGF-AB or -BB release.

Cell Division↗

[Low molecular weight heparin, reviparin, after PTCA: results of a randomized double-blind, standard heparin and placebo controlled multicenter study (REDUCE Study].

BACKGROUND: Unfractionated heparin and its low molecular fragments possess antiproliferative effects and have been shown to reduce neointimal smooth muscle cell migration and proliferation in response to vascular injury in experimental studies. OBJECTIVES: The specific objective of the REDUCE trial was to evaluate the effect of a low molecular weight heparin on the incidence and occurrence of restenosis in patients undergoing percutaneous transluminal coronary angioplasty. METHODS: The REDUCE trial is an international prospective, randomized, double-blind, multicenter study. Twenty-six centers in Europe and Canada enrolled 625 patients with single lesion coronary artery obstructions suitable for PTCA. Three hundred and six patients received reviparin as a 7000 U bolus before PTCA followed by 10,500 U as an infusion over 24 hours and then twice a day 3500 U s.c. application for 28 days. The 306 patients in the control group received a bolus of 10,000 U unfractionated heparin followed by an infusion of 24,000 U over 24 hours. These patients then received 28 days of s.c. placebo injections. The primary endpoints were efficacy (defined as a reduction in the incidence of major adverse events, i.e., death, myocardial infarction, need for reintervention or bypass surgery), absolute loss of minimal luminal diameter, and incidence of restenosis during the observation period of 30 weeks after PTCA. RESULTS: Using the intention-to-treat analysis for all patients, 102 patients (33.3%) of the reviparin group and 98 patients (32%) of the control group have reached a primary clinical endpoint (relative risk = 0.98; 95% confidence limit, 0.88-1.09; p = 0.707). Likewise, no difference in late loss of minimal luminal diameter was evident for either group. Acute events within 24 hrs occurred in 3.9% of the reviparin group and in 8.2% of the control group (relative risk = 0.49; 95% confidence limit, 0.26-0.92; p = 0.027) during or immediately after the initial procedure. In the control group, 8 major bleedings occurred, and in the reviparin group, 7 major bleeding complications were observed within 35 days after PTCA. CONCLUSIONS: Reviparin use during and after coronary angioplasty did not reduce the occurrence of major clinical events or the incidence of angiographic restenosis over 30 weeks.

Adult↗

Low molecular weight heparin (reviparin) in percutaneous transluminal coronary angioplasty. Results of a randomized, double-blind, unfractionated heparin and placebo-controlled, multicenter trial (REDUCE trial). Reduction of Restenosis After PTCA, Early Administration of Reviparin in a Double-Blind Unfractionated Heparin and Placebo-Controlled Evaluation.

OBJECTIVES: The specific objective of the REDUCE trial was to evaluate the effect of low molecular weight heparin on the incidence and occurrence of restenosis in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND: Unfractionated heparin and its low molecular weight fragments possess antiproliferative effects and have been shown to reduce neointimal smooth muscle cell migration and proliferation in response to vascular injury in experimental studies. METHODS: The REDUCE trial is an international prospective, randomized, double-blind, multicenter study. Twenty-six centers in Europe and Canada enrolled 625 patients with single-lesion coronary artery obstructions suitable for PTCA. Three hundred six patients received reviparin as a 7,000-U bolus before PTCA, followed by 10,500 U as an infusion over 24 h and then twice-daily 3,500-U subcutaneous application for 28 days. The 306 patients in the control group received a bolus of 10,000 U of unfractionated heparin followed by an infusion of 24,000 U over 24 h. These patients then underwent 28 days of subcutaneous placebo injections. The primary end points were efficacy (defined as a reduction in the incidence of major adverse events [i.e., death, myocardial infarction, need for reintervention or bypass surgery]), absolute loss of minimal lumen diameter and incidence of restenosis during the observation period of 30 weeks after PTCA. RESULTS: Using the intention to treat analysis for all patients, 102 (33.3%) in the reviparin group and 98 (32%) in the control group have reached a primary clinical end point (relative risk [RR] 1.04, 95% confidence interval [CI] 0.83 to 1.31, p = 0.707). Likewise, no difference in late loss of minimal lumen diameter was evident for both groups. Acute events within 24 h occurred in 12 patients (3.9%) in the reviparin group and 25 (8.2%) in the control group (RR 0.49, 95% CI 0.26 to 0.92, p = 0.027) during or immediately after the initial procedure. In the control group, eight major bleeding complications occurred, and in the reviparin group, seven were observed within 35 days after PTCA. CONCLUSIONS: Reviparin use during and after coronary angioplasty did not reduce the occurrence of major clinical events or the incidence of angiographic restenosis over 30 weeks.

Angioplasty, Balloon, Coronary↗

Occurrence and magnitude of pressure waves during Er:YAG laser ablation of atherosclerotic tissue: comparison to XeCl excimer laser ablation.

BACKGROUND AND OBJECTIVE: Since excimer laser ablation has not shown advantages in comparison to conventional balloon angioplasty, the search for other laser light sources came up with the Er:YAG laser, operating at a wavelength of 2.94 microns. STUDY DESIGN/MATERIALS AND METHODS: Normal and atherosclerotic human vessel segments were irradiated in vitro, using pulsed Er:YAG laser systems. The laser beam was either focused onto the tissue in air or delivered via a fibre system onto the tissue being immersed in saline. Needle-type hydrophones were used for pressure pulse detection. RESULTS: Er:YAG laser irradiation results in effective tissue ablation of normal and calcified atherosclerotic vessel segments. In comparison to excimer lasers, ablation rates can be increased by a factor of 5 to 10 at least. Er:YAG laser ablation is also associated with a generation of pressure waves. On calcified plaque, the acoustic signals differ significantly from those on normal tissue. Histological tissue analysis reveals small zones of discoloration and tissue fissures that are found 100-200 microns lateral to the crater edge, depending on the energy density used. CONCLUSION: Er:YAG lasers generate pressure waves that are comparable to excimer laser ablation. Er:YAG lasers, however, show a markedly improved ablation efficiency, which may favour these systems as effectively cutting, less traumatic tools for removal of atherosclerotic plaque.

Aortic Diseases↗

Comparison of passive and active perfusion catheters: an in vitro study in a pulsatile coronary flow model.

Perfusion balloon catheters are designed to provide continuous transcatheter blood flow and thereby reduce myocardial ischemia during coronary angioplasty. To compare the transcatheter flow rates of active and passive (auto-) perfusion catheters, a well-controlled experimental study was performed in a circulation model that duplicates the phasic, predominantly diastolic flow pattern of the left coronary artery. Mean diastolic coronary driving pressure varied between 20 and 100 mm Hg. For the autoperfusion catheters, a strong relationship between transcatheter flow and diastolic coronary driving pressure was found. For example, a coronary driving pressure of 80 mm Hg provided a coronary flow of 30 ml/min (RX-Perfusion [RP], ACS), 28 ml/min (Speedflow [SF], Schneider), 20 ml/min (Lifestream [LS], ACS), and 19 ml/min (Flowtrack [FT], ACS). Reduction of driving pressure to 40 mm Hg decreased the absolute transcatheter flow, which was now 16 ml/min (RP), 13 ml/min (SF), and 10 ml/min (LS and FT). The relative catheter flow (the ratio of absolute flow to baseline coronary flow rate without a catheter in place), was independent of actual coronary driving pressure and ranged between 21% +/- 1% (RP) and 14% +/- 1% (FT and LS). For the active perfusion system (Coreflo, Leocor, a maximal transcatheter flow of 82 ml/min was found. Using this active perfusion system, the relative catheter flow increased with decreasing coronary driving pressure:80 --> 40 mm Hg: 56% --> 107%. For all catheters, the distal perfusion decreased between 30% (3.0 mm RP) and 50% (3.0 mm LS) by a 0.014-inch guidewire placed through the inner channel of the catheter. Because of the strong relationship between coronary driving pressure and transcatheter flow, the residual flow through all autoperfusion catheters becomes critical (<20 ml/min), when the coronary driving pressure drops below 50 mm Hg. By contrast, active perfusion systems are independent of the actual coronary driving pressure and are therefore advantageous for prolonged dilation in patients with low aortic pressure.

Angioplasty, Balloon, Coronary↗

Low molecular weight heparin in prevention of restenosis after PTCA.

Late restenosis occurring after successful PTCA continues to represent a major problem limiting the clinical efficacy of the procedure. It has been shown that smooth muscle cell proliferation plays a major role in this accelerated atherosclerotic process. In vitro and in vivo experiments with the low molecular weight heparin reviparin showed a pronounced inhibitory effect by this compound on smooth muscle cell proliferation. To evaluate the safety of reviparin and the incidence of angiographic restenosis in humans, a study of increasing dosages was conducted in 41 patients. Repeat coronary angiography was performed 3 months after angioplasty. Restenosis occurred in 5 of 37 evaluable patients with initially successful PTCA. No major bleeding complication was documented for any patient in this first pilot trial. A randomized, double-blind, multicentre trial is being carried out to define the real impact of this compound in reducing restenosis in patients who undergo successful balloon angioplasty.

Angioplasty, Balloon, Coronary↗

Exercise Doppler echocardiography in conjunction with right heart catheterization for the assessment of mitral stenosis.

RATIONALE: A new diagnostic approach is reported, which combines Doppler echocardiography and a thermodilution technique for the calculation of mitral valve area at rest and during exercise. This method was applied to determine the magnitude of mitral valve reserve (= exercise-induced increase of mitral valve are) and to assess the hemodynamic relevance of mitral stenosis. METHODS: 69 patients with mitral stenosis were included in this study. A Swan-Ganz catheter was used to measure exercise hemodynamics and transvalvular flow by a thermodilution technique. The mean transmitral flow velocity vmean was determined by continuous wave Doppler. Measurements were performed simultaneously at rest and during stepwise bicycle ergometry. Effective mitral valve area was calculated according to the continuity equation method (MVACE = Flow/vmean). RESULTS: A significant exercise-induced increase of mitral valve area was found in the total group (rest-->25 W: 1.1 +/- 0.3-->1.3 +/- 0.4 cm2, p < 0.001). Two subgroups were defined according to the presence or absence of mitral valve reserve: delta MVA > and = 20%: group A (n = 30); delta MVA < 20%: group B (n = 39). Both groups did not differ with regard to mitral valve area at rest. However, the increase of cardiac output and stroke volume was significantly higher in group A than in group B. An effective mitral valve area at 25 W of less than 1.2 cm2 had an 80% sensitivity and an 83% specificity to detect a severe mitral stenosis. CONCLUSIONS: Because the presence and extent of mitral valve reserve cannot be predicted under resting conditions measurements under flow-increasing interventions are necessary. Our data demonstrate that exercise Doppler in conjunction with right-sided cardiac catheterization is most useful to determine mitral valve reserve and to assess the hemodynamic relevance of mitral stenosis.

Adult↗

Porous balloon delivery of low molecular weight heparin in the dog coronary artery.

UNLABELLED: The aim of this experimental study was to assess the safety of local delivery of low molecular weight heparin via a porous balloon in the canine coronary artery. In 16 mongrel dogs, percutaneous transluminal coronary angioplasty was performed. In addition, eight of the dogs were given 4 ml Clivarin (1500 IU) delivered locally into the coronary artery immediately after dilatation. The animals were killed after 3 or 14 days. In the animals with local administration, the results of histopathology after 3 days showed the findings to be heterogeneous with marked disruption of the internal elastic lamina in all animals, and varying degrees of medial haemorrhage, medial necrosis, perivascular haemorrhage and signs of myocardial necrosis. Similar changes, but of lesser severity, were present in the animals treated with balloon dilatation only. After 14 days, the severity of vascular and perivascular alterations (medial haemorrhage, perivascular haemorrhage, thrombus formation) was significantly lower in the local delivery group (P < 0.05), but disruption of the internal elastic lamina, as a marker of the initial trauma, was present in all the animals. The presence of residual intracoronary thrombus was only seen in the PTCA group without local delivery. CONCLUSIONS: In this safety study, both groups showed pronounced alterations in the vessel wall 3 days following percutaneous transluminal coronary angioplasty. This changed 14 days following percutaneous transluminal coronary angioplasty when intramural injection of Clivarin resulted in a marked decrease of residual thrombus and medial as well as perivascular haemorrhage. Although the additional vessel trauma by the drug delivery technique did not result in increased complications, a careful approach with this potentially harmful procedure is essential.

Angioplasty, Balloon, Coronary↗

-Diagnostic shunt oximetry of atrial septal defect in adulthood-.

UNLABELLED: There are several circumstances in which data obtained at catheterization should alert the cardiologist to look for a shunt that had not been suspected previously. Aim of the study was to explore the most sensitive parameter which is easily practicable and which gives strong evidence for an atrial septal defect (ASD). Moreover, a simplified method for quantifying left-to-right shunts was analyzed. In 84 patients (58 with an atrial septal defect and 26 patients without shunt) a complete oxygen saturation status was determined. The oxymetrically determined relation between pulmonary bloodflow QP and systemic bloodflow QS was 1.31 to 5.60 in patients with ASD and 0.75 to 1.19 in patients without shunt. The analysis of sensitivity and specificity was determined to define the marginal value which gives suspicion of an ASD. The best values for sensitivity and specificity was found for PA O2-SVC O2 = 7.4% (sens. = 98.3%, spec.= 96.2%), PA O2 -IVC O2 = 2.0% (sens./spec.= 100%), PA O2 - MV O2 = 5.0% (sens./spec.= 100%) and PA O2 = 78.4% (sens./spec. = 97.5%). The correlation between the modified ratio QP/QS and various differences in O2-saturation with the shunt size was examined. A high correlation was found for the modified QP/QS with SVC O2 instead of MV O2 (r = 0.98), PA O2-SVC O2 (r = 0.77) and PA O2 - MV O2 (r = 0.74) with QP/QS, respectively. CONCLUSION: The results demonstrate that an O2-saturation >78% in the pulmonary artery is highly suspicious for the diagnosis of an ASD. With the modified ratio QP/QS = (ART O2-SVC O2)/(PV O2-PA O2) a high sensitive and specific modus of quantifying shunts can be reached. Determination of oxygen saturation from the V. cava interior is therefore not useful.

Adolescent↗

[Coronary laser angioplasty: clinical value and experimental progress].

From 1988 to 1995, approximately 10,000 patients with coronary artery disease have been treated using excimer laser angioplasty. All data underline the feasibility and safety of this technique. However, coronary excimer laser angioplasty has been performed as a stand-alone procedure in a minority of patients, only, either due to an insufficient angiographic result, or due to complications such as abrupt vessel closure, severe dissection or perforation. Clinical and angiographic follow-up studies have also documented that excimer laser angioplasty does not reduce the incidence of restenosis following the coronary intervention. Experimental results underline the importance of pressure waves and bubble formations, which can cause additional vessel wall trauma despite thermal injury. Promising new laser devices should offer high ablation rates with only minimal thermal and acoustic tissue injury. It is expected that such laser devices will emit in the mid-infrared spectrum of light.

Angioplasty, Laser↗

[Concepts for local therapy of restenosis].

Local drug delivery is a new therapeutic approach targeted at the prevention of restenosis after coronary balloon angioplasty. Several mostly catheter-based devices have been designed to deliver medications with, for example, antithrombotic or antiproliferative actions directly at the site of angioplasty. Besides delivery of conventional pharmacologic agents, novel therapeutic strategies based on molecular mechanisms (e.g., gene transfer or antisense oligonucleotides) are currently under investigation and at the threshold of clinical trials. In addition, local radiation with either radioactive wires or stents has shown promising results in first experimental studies. More investigations are necessary, however, to clearly demonstrate the efficacy of the various local delivery approaches, with a special emphasis on safety aspects.

Angioplasty, Balloon, Coronary↗

Comparison of valvular resistance, stroke work loss, and Gorlin valve area for quantification of aortic stenosis. An in vitro study in a pulsatile aortic flow model.

BACKGROUND: Valvular resistance and stroke work loss have been proposed as alternative measures of stenotic valvular lesions that may be less flow dependent and, thus, superior over valve area calculations for the quantification of aortic stenosis. The present in vitro study was designed to compare the impacts of valvular resistance, stroke work loss, and Gorlin valve area as hemodynamic indexes of aortic stenosis. METHODS AND RESULTS: In a pulsatile aortic flow model, rigid stenotic orifices in varying sizes (0.5, 1.0, 1.5 and 2.0 cm2) and geometry were studied under different hemodynamic conditions. Ventricular and aortic pressures were measured to determine the mean systolic ventricular pressure (LVSPm) and the transstenotic pressure gradient (delta Pm). Transvalvular flow (Fm) was assessed with an electromagnetic flowmeter. Valvular resistance [VR = 1333.(delta Pm/Fm)] and stroke work loss [SWL = 100.(delta Pm/LVSPm)] were calculated and compared with aortic valve area [AVA = Fm/(50 square root of delta Pm)]. The measurements were performed for a large range of transvalvular flows. At low-flow states, flow augmentation (100-->200 mL/s) increased calculated valvular resistance between 21% (2.0 cm2 orifice) and 66% (0.5-cm2 orifice). Stroke work loss demonstrated an increase from 43% (2.0 cm2) to 100% (1.0 cm2). In contrast, Gorlin valve area revealed only a moderate change from 29% (2.0 cm2) to 5% (0.5 cm2). At physiological flow rates, increase in transvalvular flow (200-->300 mL/s) did not alter calculated Gorlin valve area, whereas valvular resistance and stroke work loss demonstrated a continuing increase. Our experimental results were adopted to interpret the results of three clinical studies in aortic stenosis. The flow-dependent increase of Gorlin valve area, which was found in the cited clinical studies, can be elucidated as true further opening of the stenotic valve but not as a calculation error due to the Gorlin formula. CONCLUSIONS: Within the physiological range of flow, calculated aortic valve area was less dependent on hemodynamic conditions than were valvular resistance and stroke work loss, which varied as a function of flow. Thus, for the assessment of the severity of aortic stenosis, the Gorlin valve area is superior over valvular resistance and stroke work loss, which must be indexed for flow to adequately quantify the hemodynamic severity of the obstruction.

Aortic Valve↗