Percutaneous aortic valve replacement: first endovascular resection of human aortic valves in situ.
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Aortic Valve↗
Biomedical subjects
Georg Lutter
Publications and source records attributed to Georg Lutter.
Percutaneous valve replacement: a novel low-profile polyurethane valved stent.
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Heart Valve Prosthesis↗
Improvement of contractility accompanies angiogenesis rather than arteriogenesis in chronic myocardial ischemia.
INTRODUCTION: Growth factor therapy provides a therapeutic alternative for "no option" patients with coronary disease. Fibroblast Growth Factor-2 (FGF-2) predominantly stimulates angiogenesis, the growth of new capillaries, whereas Monocyte Chemoattractant Protein-1 (MCP-1) is considered an arteriogenic agent. We hypothesised a synergetic effect of FGF-2 and MCP-1 in ischemic myocardium. METHODS: A severe coronary stenosis was created in pigs. After one week, chronic ischemia was confirmed by angiography, echocardiography, reduced ejection fraction, and increase of marker enzymes. FGF-2, MCP-1, both, or vector only were then injected intramyocardially as plasmid DNA in the impaired area. Regional contractility and number of capillaries and arterial vessels were evaluated after three months. RESULTS: FGF-2, FGF-2+MCP-1, and vector, but not MCP-1 alone improved regional contractility at rest, whereas only FGF-2 alone ameliorated function under stress conditions. Angiogenesis in the ischemic area was stimulated by FGF-2 compared to MCP-1. In contrast, MCP-1 induced arteriogenesis relative to FGF-2. CONCLUSION: Differences for vessel growth and regional function were apparent between FGF-2 and MCP-1. This contrast could allow the speculation that development of a flow reserve in chronically ischemic myocardium is linked to angiogenesis rather than to arteriogenesis. No additional benefits were seen following combined therapy.
Animals↗
Percutaneous pulmonary valve replacement: 3-month evaluation of self-expanding valved stents.
PURPOSE: In a recent study our group established an acute animal model of percutaneous pulmonary valve replacement using self-expanding nitinol stents. The present study was performed to evaluate these valved stents over a 3-month period. DESCRIPTION: Bovine jugular xenografts were sutured into nitinol stents. Transfemoral implantation in the pulmonary position using a modified commercially available application device (with a 22-French outer diameter) was evaluated in 9 sheep. EVALUATION: Two sheep died shortly after successful valved stent implantation due to internal venous hemorrhage. Another 1 sheep died 2.5 months after the procedure due to vegetations on the neovalve leading to subtotal stenosis. All other animals survived the 3-month study time (n = 6). An orthotopic pulmonary valved stent position was achieved in 4 animals and a supravalvular position in 1. During the deployment procedure, rhythm disturbances occurred in all animals, and mean arterial blood pressure dropped from 83.9 +/- 26.0 mm Hg to 68.3 +/- 22.3 mm Hg (p = 0.006) (n = 5). The peak-to-peak transvalvular gradient was 5.1 +/- 4.0 mm Hg initially (n = 5), and 3.6 +/- 1.6 mm Hg at follow-up (n = 5). Three-month angiographic and echocardiographic follow-up confirmed competent neovalves without paravalvular leakages. CONCLUSIONS: After 3 months of implantation, percutaneously implanted memory nitinol valved stents demonstrated good function in the sheep.
Animals↗
Midterm follow-up after minimally invasive direct coronary artery bypass grafting versus percutaneous coronary intervention techniques.
BACKGROUND: Revascularization of the left anterior descending coronary artery can be performed by minimally invasive direct coronary artery bypass grafting (MIDCAB) or percutaneous coronary intervention techniques (PCI). The study compared the midterm results of both techniques. METHODS: The outcome of 206 consecutive MIDCAB and 256 PCI patients treated from 1998 until 2001 was retrospectively analyzed. Cardiologists determined the primary patient allocation for the distinct revascularization technique. Periprocedural complications and midterm follow-up, including quality-of-life assessment (SF-36), was reported up to 5.2 years (3.4 +/- 0.7 years). RESULTS: Periprocedural and overall mortality (p = 0.206) showed no differences. Four MIDCAB patients required early reoperation but not for repeated target vessel revascularization. In 16 patients secondary PCI (7.8%) of other coronary vessels was performed. Repeated revascularization of the left anterior descending coronary artery was necessary in 24.2% of patients in the PCI group (p < 0.001), with 4.7% finally requiring surgical revascularization. The incidence of major adverse cardiac events, including myocardial infarction (p = 0.581), repeated target vessel revascularization (p < 0.001), or death (p = 0.206) was higher in the PCI group. This difference consisted basically of the need for repeated target vessel revascularization. Patient-based quality-of-life assessment (SF-36) was independent from the primary chosen revascularization method. CONCLUSIONS: At midterm follow up, MIDCAB resulted in significantly superior results regarding the need for repeated target vessel revascularization compared with PCI, with no significant differences regarding other major cardiac events.
Adult↗
Advances in experimental percutaneous pulmonary valve replacement.
BACKGROUND: Percutaneous pulmonary valve implantation is emerging as an alternative and additional option for a successful surgical scheme. To date, these procedures are performed by the balloon-in-balloon technique. The use of self-expanding stents for percutaneous valve replacement is assumed to improve preservation of the valve in its folded condition in the application device and the valve's long-term functioning. Therefore, initial experience with the development of a completely percutaneous transfemoral technique for pulmonary valve implantation using a self-expanding valved stent is described. METHODS: Bovine jugular xenografts were sutured into nitinol stents, and functional in vitro tests of valved stents were carried out. Transfemoral implantation in pulmonary position was acutely evaluated in 6 sheep weighing 22 to 29 kg. Radiologic evaluation was performed by angiography and multislice computed tomography (MSCT) scan. In addition, pathoanatomical studies were performed. RESULTS: Exact implantation in pulmonary valve position was achieved in 5 of 6 sheep, with 1 early stent migration. Another sheep died before stent placement owing to perforation of the right ventricle by the delivery system. Orthotopic pulmonary valved stent position was depicted by MSCT in all other sheep (n = 4). The peak-to-peak transvalvular gradient was 8.2 +/- 3.9 mm Hg (n = 5). Postmortem examination revealed intact stent valves with no adherent clots. No macroscopic damage of the pulmonary artery was noted, whereas minor hematoma of the right atrium and the right ventricular outflow tract were observed in 2 hearts. CONCLUSIONS: This acute study demonstrates that memory nitinol valved stents can be optimally deployed in the pulmonary position through the groin in sheep.
Animals↗
Percutaneous aortic valve replacement: resection before implantation.
OBJECTIVE: After transluminal endovascular implantation of a new valved stent, the aim of this study was to evaluate the feasibility of using a high-pressure water stream to endovascularly resect human calcified aortic valves. METHODS: First, human calcified aortic valves were excised and then resected in vitro to determine optimal water jet parameters. Second, healthy porcine aortic valves were ablated in vitro to evaluate possible destruction to the surrounding anatomy. Third, resection was performed endoluminally by introducing microsystemic tools into the descending aorta, passing them through the arch and ascending aorta to the aortic valve in an in vitro porcine model. Macro- and micropathology of specimens were analyzed. RESULTS: First, resection of human calcified valves took a mean of 6.0+/-2.4min per three leaflets at 150bar (n=17). The maximum size of the cut leaflets was 7.1+/-1.7mm. Second, resection of healthy porcine aortic valves at 60bar took 2.3+/-0.3min per three leaflets (n=10). Only the aortic annulus was moderately affected in six cases. Third, endoluminal resection via the descending aorta took 12.2+/-0.8min per three leaflets at 60bar (n=10). The aortic wall was affected in four cases, the aortic annulus and the coronary ostia only once. Microscopic analysis also revealed superficial lesions with a maximum lesion depth of 1200microm in one case, and an average of 580+/-145microm in subsequent lesions. The mitral valve and the left ventricular outflow tract were not affected. CONCLUSIONS: Percutaneous resection of heart valves is emerging as a promising auxiliary method for the resection of calcified aortic heart valves because they can be cut endoscopically. Nonetheless, before this resection tool can be clinically applied by surgeons to perform a true percutaneous valve replacement, an additional aortic valve resection chamber (already at the prototype stage) designed for capturing all debris, has to be established.
Animals↗
Percutaneous valve replacement: current state and future prospects.
Percutaneous valve implantation is the development of a foldable heart valve that can be mounted on an expandable stent delivered percutaneously through standard catheter-based techniques and implanted within a diseased valve annulus. In cases with severe aortic stenosis, the diseased valve has to be pre-dilated. To perform a true replacement the diseased valve has to be ablated and removed. In this article, we review the development of percutaneous valve replacement technology and discuss future prospects in this field.
Forecasting↗
Effects of acute systemic endothelin receptor blockade on cardiac electrophysiology in vivo.
BQ-123, a selective endothelin-A receptor antagonist, has been demonstrated to suppress arrhythmias. However, the role of physiologic levels of endogenous endothelin-1 (ET-1) with respect to electrophysiologic properties of the heart is unknown. BQ-123 (0.45, 0.9, 1.8, 3.6, 7.2, and 14.4 microg/kg/min; n = 10) or saline (control, n = 5) was administered IV for 15 minutes of continuous-rate infusion at incremental doses to anesthetized normal pigs. BQ-123 had no effect on PR and QT interval, QRS duration, intraatrial and AV nodal conduction time as well as the atrial, AV nodal, and ventricular effective refractory periods. As compared with baseline, BQ-123 at 7.2 and 14.4 microg/kg/min caused an increase in heart rate (99 +/- 17 versus 110 +/- 14 and 118 +/- 14 bpm, respectively; P < 0.05), shortened sinus node recovery time (818 +/- 165 versus 641 +/- 69 and 609 +/- 74 milliseconds, respectively; P < 0.05) and decreased mean arterial pressure at 14.4 microg/kg/min (95 +/- 18 versus 80 +/- 11 mm Hg; P < 0.05). We conclude that in the normal pig, physiologic levels of ET-1 have no effect on conduction properties of atrial, AV nodal, or Purkinje fibers. However, antagonism of ET-1 by BQ-123 unmasks the effect of ET-1 on maintenance of vasomotor tone, which in turn may affect heart rate and sinus node automaticity in the intact pig.
Animals↗
Percutaneous aortic valve replacement: more than palliation?
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Aortic Valve↗
Myocardial viability twenty-four hours after orthotopic heart transplantation from non-heart-beating donors.
OBJECTIVES: Using a new preservation strategy, we investigated the performance of hearts from non-heart-beating donors during an observation period of 24 hours after orthotopic heart transplantation in a pig model. METHODS: In the control group (n = 6) beating donor hearts were harvested with Bretschneider's HTK solution and transplanted orthotopically without reperfusion modifications. In the non-heart-beating donor group (n = 6) hearts were perfused with leukocyte-depleted blood cardioplegia after 30 minutes of normothermic ischemia. Blood cardioplegia was supplemented with a sodium-hydrogen exchange inhibitor and adenosine. After transplantation, a second controlled reperfusion with blood cardioplegia was performed. RESULTS: Preload recruitable stroke work of the left ventricle 24 hours after transplantation in the control versus non-heart-beating donor group was 108% +/- 24% versus 103% +/- 18% of baseline values. Myocardial blood flow of the left and right ventricle was increased to 146% +/- 32% and 176% +/- 51% in the control group versus 176% +/- 29% and 194% +/- 27% in the non-heart-beating donor group. Myocardial oxygen consumption was 11.2 +/- 2.1 versus 12.8 +/- 2.2 mL/100 g per minute at baseline and 11.6 +/- 2.6 versus 13.2 +/- 3.1 mL/100 g per minute after 24 hours (not significant). Histologic examination with Luxol fast blue staining revealed that 2.6% +/- 4.8% of myocytes in the control group versus 1.8% +/- 1.9% in the non-heart-beating donor group were damaged irreversibly. CONCLUSIONS: Recovery of donor hearts from non-heart-beating donors is comparable with recovery of organs harvested from heart-beating donors if the above-mentioned preservation technique is used. These results could encourage the use of marginal donor hearts and help to expand the limited donor pool.
Animals↗
Transmyocardial laser revascularization combined with vascular endothelial growth factor 121 (VEGF121) gene therapy for chronic myocardial ischemia--do the effects really add up?
OBJECTIVE: Different therapy strategies for coronary disease in conventionally untreatable patients have been developed, among them transmyocardial laser revascularization (TMLR) and the application of growth factors. The objective of our study was to determine whether a combined therapy of TMLR with a vascular endothelial growth factor(121) (VEGF(121)) plasmid is able to stimulate the development of sufficient collateral circulation and hereby to preserve cardiac function. MATERIALS AND METHODS: A severe stenosis of the left anterior descending artery was created in healthy pigs. After 1 week, perfusion and regional contractility were assessed at baseline. Afterwards, the ischemic area was treated with TMLR (n=8), intramyocardial injection of naked plasmid DNA encoding VEGF(121) (n=7), or both (n=7). Control animals were left untreated (n=8). After 3 months, the animals were re-examined and underwent immunohistological analysis. RESULTS: The number of capillaries increased only after injection of VEGF(121) plasmid alone compared to untreated ischemia and to the other therapy groups, whereas the number of arterioles was higher following TMLR treatment alone or in combination with VEGF(121) than it was in the case in untreated ischemic animals. However, only combined VEGF(121)+TLMR therapy resulted in an improvement in regional myocardial blood flow in comparison with 1 week ischemia, indicating the efficient development of collateral circulation. In contrast, better regional contractility compared to the 1-week baseline, as well as restoration of the pre-ischemic values, were achieved by both VEGF(121) and combined VEGF(121)+TLMR therapies. CONCLUSIONS: This study of chronic myocardial ischemia with a porcine model indicates a synergistic action of TMLR and VEGF(121) gene therapy. Combined treatment alone achieved an increase of regional myocardial perfusion, which accompanied arteriogenesis and corresponded with the restoration of regional function.
Animals↗
Gene therapy in cardiac surgery: intramyocardial injection of naked plasmid DNA for chronic myocardial ischemia.
OBJECTIVE: Growth factor gene therapy represents one current approach in the therapy of myocardial ischemia. We assessed the in vitro and in vivo expression of naked plasmid DNA aiming at preservation of function in a chronically ischemic myocardial model. METHODS: In vitro: Primary cardiac fibroblasts were transfected with plasmids encoding enhanced green fluorescent protein, human VEGF(121), human FGF-2, or porcine MCP-1. Protein synthesis was assessed microscopically, by ELISA, Western blotting, or intracellular immunofluorescence. In vivo: A LAD stenosis was created in healthy pigs. One week later, segmental myocardial shortening (SMS) and systemic hemodynamics (left ventricular stroke work index, LVSWI, time derivative of left ventricular pressure, dp/dt(max)) were assessed at baseline. Afterwards, the ischemic area received either intramyocardial injections of naked cytokine plasmid DNA or vector only, or was left untreated. One myocardial sample taken 1 h after plasmid injection was subjected to RT-PCR and PCR. After 3 months, cardiac function was re-examined. RESULTS: In vitro: Transfection of cardiac fibroblasts resulted in high gene expression for several days. In vivo: Plasmid-specific DNA and mRNA were found 1 h after plasmid injection (n=1). After 3 months, VEGF, FGF-2, and vector rendered better results of regional contractility at rest and of LVSWI. However, only VEGF and FGF-2 were effective with regard to regional contractility under dobutamine stress and to left ventricular contractility. CONCLUSION: In conclusion, intramyocardial injection of naked plasmid DNA encoding VEGF(121) or FGF-2 improved myocardial function in chronic ischemia in more aspects than vector only and was superior to untreated ischemia or MCP-1. This strategy can be considered a successful tool for growth factor stimulated preservation of function in chronic myocardial ischemia.
Animals↗
Three-dimensional echocardiographic determination of cardiac output at rest and under dobutamine stress: comparison with thermodilution measurements in the ischemic pig model.
Determination of cardiac output is a potentially important clinical application of three-dimensional (3-D) echocardiography since it could replace invasive measurements with the Swan-Ganz-catheter. To date, there are no studies available to determine whether cardiac output measured by thermodilution can be predicted reliably under changing hemodynamic conditions. Fifteen pigs with ischemic myocardium were examined under four hemodynamic conditions at rest and under pharmacological stress with 5, 10, and 20 microg/kg/min dobutamine. The 3-D datasets were recorded by means of transesophageal echocardiography. The endocardial definition was enhanced by administering the contrast agent FS069 (Optison). Cardiac output was calculated as the product of stroke volume (end-diastolic - end-systolic volume) and heart rate. The invasive measurements were performed with a continuous thermodilution system. In general, there was moderate correlation between 3-D echocardiography and thermodilution(r = 0.72, P < 0.001). At rest, the 3-D echocardiographic measurements were slightly but significantly lower than the invasive measurements (mean difference 0.6 +/- 0.5L/min,P < 0.001). Under stress with 5, 10, and 20 microg/kg/min dobutamine, there was a marked increase in the deviation (1.3 +/- 0.5L/min,P < 0.001; 1.6 +/- 0.7 L/min,P < 0.001; and 2.1 +/- 1.1L/min,P < 0.001, respectively). The deviation was based on two factors: (1). Under stress, the decreasing number of frames per cardiac cycle acquired with 3-D echocardiography led to imprecise recording of end-diastolic and end-systolic volumes, and thus to an underestimation of cardiac output. At least 30 frames per cardiac cycle are needed to eliminate this effect. (2). There is a systematic difference between 3-D echocardiographic and invasive measurements, which is independent of the imaging rate. This is based on an overestimation of the true values by thermodilution. In conclusion, cardiac output can be determined correctly by 3-D echocardiography for normal heart rates at rest. At elevated heart rates, the temporal resolution of 3-D systems currently available is not adequate for reliable determination. In performing and evaluating future clinical comparative studies, the systematic difference between 3-D echocardiography and thermodilution, based on overestimation by thermodilution, must be taken into account.
Animals↗
Blood cardioplegia filtration.
The introduction of blood cardioplegia has been proven to limit ischaemia and reperfusion injury in cardiac surgery. But the presence of activated neutrophils in the capillary bed may cause further damage. Leukocyte filters have been shown to be very effective in reducing the leukocytes in blood cardioplegia to less than 10%. Leukocyte depletion of blood cardioplegia provides an excellent approach to minimizing myocardial injury, predominantly in high-risk cardiac surgery.
Animals↗
Collateral growth: cells arrive at the construction site.
Coronary artery disease (CAD) and peripheral artery occlusion disease are the most common diseases in the Western world which are treated by pharmacological and surgical therapies. However, patients in the endstage of the disease are not suitable candidates for bypass surgery. Alternative therapies that boost the endogenous collateralization are required. Two mechanisms are naturally activated after onset of ischemia: 1. angiogenesis, sprouting of capillaries, and 2. arteriogenesis, enlargement of small preexisting arterioles. In the first part of this review, we describe the sequence of events during the development of collateral vessels. The second part focuses on two types of cells which are crucial for the development of collateral circulation, and which migrate to the site of vessel growth via peripheral blood: monocytes/macrophages and endothelial progenitor cells. The role of these cells and the implications for their use in treating ischemic diseases of cardiac and sceletal muscle are discussed.
Arterial Occlusive Diseases↗
The combined use of transmyocardial laser revascularization (TMLR) and fibroblastic growth factor (FGF-2) enhances perfusion and regional contractility in chronically ischemic porcine hearts.
OBJECTIVE: The purpose of this study was to determine the combined effect of transmyocardial laser revascularization (TMLR) and recombinant human basic fibroblastic growth factor (rhFGF-2) treatment in chronically ischemic hearts. METHODS: To employ this porcine ischemic model, an operative severe stenosis of the left anterior descending artery (LAD) was created (first operation). One week later, the animals were studied at baseline (second operation) by analyzing perfusion (microsphere technique) and regional contractility (ultrasonic crystals). Afterwards, pigs were randomized into one of the four groups: ischemic control group (n = 7), TMLR-group (n = 7), FGF-2-group receiving 500 microg rhFGF-2 (n = 6), and FGF-2 + TMLR-group receiving TMLR with 500 microg rhFGF-2 (n = 6). Twelve weeks later, the animals were re-examined (third operation) and the hearts underwent additionally histochemical and immunohistologic analysis. RESULTS: Three months after therapy, regional myocardial blood flow (RMBF) in the LAD territory was significantly higher at rest in the FGF-2 group and FGF-2 + TMLR group compared to baseline, control and TMLR group (FGF-2 group: 1.17 +/- 0.10 versus baseline 0.28 +/- 0.10, P = 0.028; versus control 0.49 +/- 0.12, P = 0.01; and versus TMLR 0.34 +/- 0.20, P = 0.0081; FGF-2 + TMLR group: 0.88 +/- 0.29 versus baseline 0.41 +/- 0.14, P = 0.028; versus control 0.49 +/- 0.12, P = 0.019 and versus TMLR group 0.34 +/- 0.20 ml/g per min, P = 0.0032). Furthermore, the FGF-2 + TMLR-group demonstrated higher RMBF values in the LAD territory under stress conditions compared to baseline (1.79 +/- 0.69 versus 0.41 +/- 0.14; P = 0.028) and control (1.79 +/- 0.69 versus 0.78 +/- 0.55 ml/g per min; P = 0.038) at the end of the study. In contrast to these groups, RMBF in the control and TMLR group was unchanged. After 3 months, the FGF-2- and FGF-2 + TMLR-groups' regional contractility in the LAD territory revealed an improvement at rest (FGF-2: 84.00 +/- 26.22 versus baseline: 53.76 +/- 13.49, P = 0.003; FGF-2 + TMLR: 104.46 +/- 28.62 versus control: 61.27 +/- 5.13; P = 0.005 and versus TMLR: 59.74 +/- 41.23%; P = 0.041), whereas control and TMLR animals did not show any difference. TMLR as well as FGF-2 + TMLR treatment resulted in an increased number of capillaries and of arterioles in the channel area compared to untreated ischemia (P < 0.005). CONCLUSIONS: In contrast to the TMLR- and control group, CO(2)-laser revascularization combined with the application of intramyocardial growth factor, FGF-2, significantly ameliorates perfusion at rest and stress in this model of chronic regional ischemia, whereas sole FGF-2 application showed an improvement at rest only. This was mirrored by an enhancement of regional contractility in the FGF-2 + TMLR- and FGF-2-group at rest.
Animals↗
Comparison of protein with DNA therapy for chronic myocardial ischemia using fibroblast growth factor-2.
OBJECTIVE: Treatment of coronary disease by growth factors has become an increasingly used strategy for otherwise untreatable patients and is subject to a number of clinical studies. The aim is to stimulate the development of a sufficient collateral circulation and hereby to rescue cardiac function. The objective of our study was to compare the effectiveness of fibroblast growth factor-2 (FGF-2) as protein and as naked plasmid DNA in a porcine model of chronic myocardial ischemia. MATERIALS AND METHODS: A severe stenosis of the left anterior descending artery (LAD) artery was created in healthy pigs. After 1 week, perfusion and regional and global contractility was assessed at baseline at rest and under stress. Afterwards, recombinant FGF-2 (n=6) or naked plasmid DNA encoding FGF-2 (n=7) was intramyocardially injected into the LAD territory. Control animals were left untreated (n=5). After 3 months, the animals were re-examined and underwent immunohistologic analysis. One animal received an Enhanced Green Fluorescent Protein plasmid. RESULTS: Plasmid-dependent protein synthesis was present in cardiomyocytes. FGF-2 protein as well as plasmid injections resulted in an increased number of capillaries and of arterioles compared with untreated ischemia. The improvement of the regional myocardial blood flow by FGF-2 plasmid therapy at rest might however indicate the effectiveness of the DNA application for the induction of a collateral circulation. A benefit from FGF-2 plasmid therapy was revealed with regard to regional contractility. Systemic hemodynamics were partially improved following plasFGF-2 treatment. CONCLUSIONS: In this porcine model of chronic myocardial ischemia, intramyocardial injection of FGF-2 plasmid was more effective than of FGF-2 protein in improving regional perfusion and contractility compared to untreated ischemia.
Animals↗