Search

OBJECTIVES: Since blood flow impairment by aortic valve prosthesis is characteristically dynamic, this dynamic component is best and thoroughly appreciated by exercise Doppler echocardiography. We sought to determine the haemodynamics of a new pericardial aortic bioprosthesis [Trifecta™-aortic valve bioprosthesis (T-AVB), St Jude Medical, MN, USA] at rest and during exercise and a 10-min recovery period in comparison with alternative aortic valve prostheses, e.g. Ross operation (RO), stentless aortic valve [Medtronic freestyle-aortic valve bioprosthesis (MF-AVB)] and a healthy control group (CO). METHODS: Haemodynamics at rest and during supine exercise stress testing and a 10-min recovery period were evaluated in 32 patients (mean age: 70.8±6.7 years) with T-AVB (mean follow-up: 5±2 months), 49 with RO (mean age: 43.5±13.7 years), 39 with an MF-AVB (mean age: 64.6±9.4 years) and 26 healthy patients (mean age: 39±9 years). Measurements included mean outflow tract gradient (δp mean, mmHg), effective orifice area index (EOAI, cm 2 /m 2 ) and valvular resistance (vR, dyn s cm −5 ). RESULTS: Mean body surface area for T-AVB was 1.93±0.24 m 2 (median 1.97 m 2 ). Mean δp mean at rest was 7.2±3.4 mmHg, mean EOAI 0.86±0.23 cm 2 /m 2 and mean vR 50.7±23.2 dyn s cm −5 . Supine stress testing did increase the mean EOAI to 0.98±0.27 cm 2 /m 2 ,t he mean vR to 62.6±25.3 dyn s cm −5 and the mean δp mean to 10.21±4.7 mmHg, respectively (P more...

Background: The Ross operation provides the advantage of growth potential of the pulmonary autograft in the aortic position. However, development of autograft dilatation and regurgitation may occur. We sought to assess the progression of autograft diameters and aortic regurgitation (AR) with regard to patient age at the time of the Ross operation. Methods: Autograft echo dimensions from 48 children Results: The mean z values of all patients showed a significant increase with follow-up time at the sinus (0.5 ± 0.1/year, P < .001) and the sinotubular junction (0.7 ± 0.2/year, P < .001) but not at the annulus (0.1 ± 0.1/year, P = .59). There was no significant difference in the z values of sinus and the sinotubular junction between younger and older children at implantation and with time. The initial annulus z value was significantly larger in younger children ( P < .0001), whereas the annual increase was significantly higher in older children ( P = .021). Age at operation has no impact on the initial AR grade ( P = .60). The AR tends to increase more quickly in older patients ( P = .040). Sinus and sinotubular junction dilate with time, regardless of patient age. Conclusions: Young children show larger initial annulus sizes than older children. However, annulus diameters tend to normalize in young children, whereas they increase in older children. Autograft regurgitation develops slowly, but significantly, and predominantly in older children. Stabilizing measures to prevent autograft root dilatation are warranted in adolescents, but they are not required in young children. more...

Left ventricular assist device implantation disrupts the natural intracavitary blood flow path through the heart, introducing flow patterns potentially associated with thrombosis, especially around the inflow cannula. We describe a novel technique for completely excluding the left ventricle with an assist device by using a cone shaped ring-reinforced prosthesis. more...

Dilatation of the ascending aorta is a common occurrence in patients with bicuspid aortic valve (BAV). The aim of the current study was to characterize collagen content in advanced glycation end products (AGEs) of dilated aortic tissue from two distinct areas, concave and convex aortic sites in patients with BAV and TAV. Collagen contents extracted from 100 mg tissue was isolated by enzymatic digestion using pepsin and the nondigested material was further digested using cyanogen bromide, insoluble collagen fraction (ICF) was extracted by hydrochloric acid hydrolysis. BAV tissue showed diminished fluorescence of the pepsin extracted fraction (PEF) compared with TAV tissue (12.4 ± 1.0% vs 32.9 ± 7.6%, p = 0.05). Patients with BAV had PEF of collagens significantly diminished in the dilated ascending aorta, especially in its convex portion, in course of aging and increment of dilated diameters. It is suggestible that BAV patients present more highly AGE-modified collagens in their ascending aorta. more...

Our aim is to investigate the elevation of matrix proteins in tissues obtained from distal, above the sinotubular junction (proximal), concave, and convex sites of aneurysms in the ascending aorta using a simultaneous multiplex protein detection system. Tissues were collected from 41 patients with ascending aortic aneurysms. A total of 31 patients had a bicuspid aortic valve (BAV), whereas 10 had a tricuspid aortic valve (TAV). Concave and convex aortic site samples were collected from all patients, whereas proximal and distal convexity samples were obtained from 19 patients with BAV and 7 patients with TAV. Simultaneous detection of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) was performed at each of the four aortic sites. MMP-2 levels were higher in the concave aortic sites than in the convex aortic sites. In contrast, MMP-8 levels were higher in the convex sites than in the concave sites, as were MMP-9 levels. In both BAV and TAV patients, TIMP-3 levels were higher in the concave sites than in the convex sites. However, TIMP-2 and TIMP-4 levels were significantly elevated in the sinotubular proximal aorta of BAV patients. Simultaneous detection of MMPs and TIMPs revealed different levels at different aortic sites in the same patient. more...

OBJECTIVES: The Ross operation in the setting of a bicuspid aortic valve (BAV) remains controversial. Using data from the German Ross Registry, we sought to investigate the effect of the presence of a BAV on autograft function and diameters over time after the Ross operation compared with the presence of a tricuspid aortic valve (TAV). METHODS: A total of 1277 patients (mean age 42.2 + or - 15.3 years) with intra-operatively documented aortic valve morphology during the Ross operation were analysed in the present study (sub-coronary technique, n=648, root replacement technique, n=629 patients). A BAV was present in 70.9% of patients. Clinical and echocardiographic follow-up was performed preoperatively and at pre-specified intervals (mean follow-up 5.7 + or - 3.8 years, 6806 patient-years). Hierarchical multilevel modelling techniques were used for the statistical analysis of serial measurements and comparisons among groups. RESULTS: Initial neo-aortic regurgitation was lower in the BAV group (0.52 vs 0.62 aortic insufficiency (AI) grades, p=0.008), whereas the annual increase of it did not differ among groups. In both surgical techniques, no significant development of neo-aortic regurgitation ( more...

Apoptosis of vascular smooth muscle cells (VSMCs) is involved in bicuspid aortic valve (BAV) ascending aorta aneurysms characteristically affecting the convex site. Caspase-3 is a pivotal effector of the apoptosis machinery. The aim of this study was to investigate the impact of an inhibited caspase-3 pathway on apoptosis in convex and concave sites VSMCs of ascending aortic tissue in vitro. Specimens from the convex and concave sites of ascending aortic aneurysm were collected from nine patients with BAV (mean age 58.7+/-14.8). Cultured VSMCs were characterized morphologically and immunohistochemically. Apoptosis activity was measured in VSMCs using Annexin V-APC with propidium iodide nuclear staining in flow cytometry. To investigate apoptotic modulation, caspase-3 was inhibited by N-acetyl-Asp-Glu-Val-Asp-CHO (Ac-DEVD-CHO). Apoptosis was initiated by calcium chloride. Inhibition of caspase-3 with Ac-DEVD-CHO protected VSMCs against calcium chloride apoptosis significantly more in the concave site than in the convex site (25.8+/-9.8 versus 38.5+/-8.0% apoptotic cells, p=0.01). Morphological scanning using light microscopy revealed typical VSMCs. We provide evidence that VSMCs show a different behavior with respect to apoptosis in the concave versus the convex sites in BAV ascending aortic aneurysm. Inhibition of caspase-3 resulted in a significantly increased protection of VSMCs against apoptosis in the concave site compared with the convex site in ascending aortic aneurysm in BAV. These findings may have some implications on understanding aneurysmal formation and its potential modulation. more...

Objective: The use of stentless bioprostheses for aortic valve replacement provides excellent haemodynamics; however, these valves bear the potential risk of progressive regurgitation over time. To overcome this disadvantage, a new generation of pericardial stentless prostheses has been developed. This study aims to assess the tolerance of such bioprotheses against progressive sinotubular junction dilatation. Methods: Five specimens of both the 3F Aortic and Sorin Solo stentless bioprotheses (diameter 25 mm) were investigated in a pulsatile flow simulator incorporating a device for gradual expansion of the sinotubular junction diameter. Closing characteristics were obtained by high-speed video imaging and the corresponding regurgitations were determined by ultrasonic flow measurements. The diameters DR, at which primary distinct regurgitation occurs, were correlated to the original diameters DA and expressed as percentage values. Results: The highest tolerance against sinotubular junction dilatation was found for the 3F Aortic (156 5%) compared to the Sorin Solo (145 6%, p = 0.0127) bioprothesis. Visualisation of the valves revealed strong leaflet folding at labelled diameter, similar in both valve types. Conclusions: New-generation pericardial stentless bioprotheses provide favourable adaptability to sinotubular junction dilatation, more pronounced for the 3F prosthesis. Whether undue leaflet folding caused by the redundant tissue influences long-term function remains to be established. # 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved. more...

OBJECTIVE: Transmyocardial laser revascularization for angina relief and intramyocardial autologous endothelial progenitor cell injection for neoangiogenesis may offer a new treatment strategy for patients with intractable ischemic heart disease. METHODS: Transmyocardial laser revascularization and intramyocardial injection of bone marrow-derived CD133+ cells was performed in six highly symptomatic patients. Transmyocardial laser channels were created and isolated CD133+ cells were injected intramyocardially. All patients were followed up for a minimum of 6 months postoperatively. RESULTS: One patient died shortly after the operation due to refractory heart failure. In the five survivors, CCS class improved as well as left ventricular ejection fraction. Left ventricular end-diastolic volume and myocardial perfusion varied between the patients. All patients described a considerable improvement in quality of life postoperatively. Repeated 24-hour Holter monitoring revealed no significant arrhythmias. CONCLUSIONS: In this small patient cohort, intramyocardial CD 133+ cell injection combined with transmyocardial laser revascularization led to an improvement in clinical symptomatology in all patients and in left ventricular function in 4 out of 5 patients, with an unclear effect on myocardial perfusion. Caution is advised when employing this therapy in patients with severely depressed left ventricular function. more...

Background Valve competence in valve-sparing aortic root replacement has been described as being influenced by commissural height as well as graft size. The aim of this study was to investigate the impact of a gradual reduction of commissural height and graft diameter on aortic insufficiency under physiological conditions in an IN VITRO model. Methods Porcine aortic valves were reimplanted into a tubular graft and a native commissural height was obtained. Subsequently the height was reduced by 10 % and 20 %, respectively. To investigate the impact of graft size, a 30 % reduction of the prosthesis diameter was carried out in valves with both native and reduced commissural heights. All conditions were investigated under pulsatile flow simulation and static pressure exposure. Results Reduction of commissural height caused regurgitation at both 10 % and 20 % lower heights, which was more pronounced in grafts with 20 % reduction. Graft undersizing resulted in significant reflux, with regurgitation even occurring with valves in a native commissural position. Conclusions Valve competence is impaired both by the reduction of commissural height and by reduced graft size. In particular, reimplantation of aortic valves into undersized grafts promotes valve insufficiency even if commissural height is well adjusted. more...

A major concern with mechanical heart valve prostheses is still the need for lifelong anticoagulation to prevent valve thrombosis and thrombembolism. Knowledge of the localization of initial thrombus formation on the prosthesis may help to improve valve design. Since observation of early clot deposition in vivo is difficult, the aim of this study was a detailed assessment of the initial stages of thrombus formation at bileaflet mechanical heart valves by means of an in-vitro clotting model. Four different bileaflet mechanical heart valves (St. Jude Medical, CarboMedics, ATS and On-X) were investigated in a mock circulation in aortic position using enzyme-activated milk resembling blood clotting potential. Initial development of clot formation on the valves was documented photographically and frequency of occurrence was analyzed for both location and valve type. For the bileaflet valves, clot depositions could be found in a distinct pattern similar in all types. In initial stages, clots developed downstream of the leaflets near the orifice ring, 61.5+/-5.8% of which were hinge associated, but 38.5+/-5.8% were located isolated laterally and medially remote of the hinge region, providing new information on thrombus formation potentially useful for improvement of valve design. more...

Acute aortic dissection (AAD) is a common fatal disease that affects the aorta and requires an urgent clinical intervention. A clinical feature of AAD is the characteristic tearing retrosternal pain often confused with that of myocardial infarction. In type A after Stanford, the biluminal progression is in the ascending aorta, the lethality of all untreated patients is about 50% within the first 48 hours. Most of AAD patients do not present a known connective tissue disorder. This makes the diagnosis more difficult and often late established. Similar as in myocardial infarction, a rapid test for the diagnosis establishment would be vitally helpful. This review summarizes, with examples taken from recent patents, novel strategies maintaining the development and validation of biomarkers of acute aortic dissection and compares them to known biomarkers of myocardial infarction. more...

Background The Ross procedure has gained increasing interest as an attractive alternative to a prosthetic aortic valve substitute within the last decade. Because of a probably better resistance to infection as one of its advantages, the pulmonary autograft is theoretically preferable for active endocarditis. Methods Between June 1994 and July 2003, the Ross procedure was performed using the subcoronary and inclusion technique in 296 patients (231 male, 65 female). Twenty patients had an active endocarditis of the aortic valve at the time of operation. A bicuspid valve was present in 10 patients. One patient had previous aortic valve surgery. Clinical and echocardiographic follow-up was complete. Results Early mortality was 1, late mortality was 0. There were no recurrence of endocarditis and no neurologic events during the mean follow-up of 47.3 ± 28.6 months. All patients were in New York Heart Association class I. Mean and maximum pressure gradient across the autograft was 3.5 ± 2.0 and 6.5 ± 3.4, respectively, with no autograft insufficiency in 15, 1+ in 4. Comparing postoperative with the last investigations, there were no significant changes of pressure gradients or grade of regurgitation. Mean and maximum homograft pressure gradients were 7.9 ± 3.7 and 16.2 ± 8.1 mm Hg, respectively, at last investigation; most patients had no or mild homograft regurgitation (0+, n=13; 1+, n=5; 2+, n=1). Conclusions Native valve endocarditis can be treated with excellent results using the Ross procedure with the subcoronary and inclusion technique, with low mortality and morbidity rates and a very low recurrence rate of endocarditis. more...

The aortic valve consists of three cusps attached to the wall of the aortic root. During the cardiac cycle, the aortic root undergoes complex movements that precede and aid opening and closing of the aortic valve. The aortic valve cusps themselves form thin-walled pocket-like structures, made from specialized tissue with fibrous, elastic, nervous, and muscular properties. The complex interactions of this tissue with the aortic root and within the cardiac cycle are only incompletely understood yet. In summary, the aortic valve is a complex structure which shows a perfect function in systole and diastole and under a wide range of hemodynamic conditions. No valve prosthesis (so far) can keep up with the function of the native aortic valve. Therefore, surgical techniques have been invented that aim at sparing the aortic valve or replacing it with very similar autologous tissue. Besides the resulting (near) normal valve function, one appealing advantage of these techniques is that oral anticoagulation can be abandoned completely. If the valve cusps themselves are normal, but the aortic root is aneurysmatic or dissected (with or without resulting secondary aortic insufficiency), the aortic valve can be spared by resecting the aortic root tissue and replacing it by a vascular graft. The aortic valve can then be implanted into the vascular graft in a way described by David, or can be remodeled into it (Yacoub technique) - in this case, the graft first needs to be incised at its base so that the three commissures of the valve can be sewn into the three incisions. This way pseudosinuses within the vascular graft are created. The sinuses within the aortic root are considered important for aortic valve function and coronary perfusion. On the other hand, incisions at the base of the vascular graft harbor the potential for redilatation of the aortic root because of a missing circular fixation. Such a fixation is achieved by the David technique. Therefore, there is a great debate in the surgical community which valve-sparing technique is the best and numerous modifications of the original techniques exist. A clear clinical advantage of one technique over the other could not be demonstrated so far, but many authorities advise that the David technique is to be used preferentially in patients with Marfan's syndrome (or other connective tissue disorders) and those with a very wide basal aortic root. If the aortic valve cusps themselves are diseased and cannot be reconstructed, the autologous pulmonary valve is the most physiological substitute. Replacing the aortic valve with the autologous pulmonary valve is named Ross procedure. The defect in the right ventricular outflow tract that is created while harvesting the autograft must be reconstructed during the same procedure; usually, a pulmonary valve allograft is used for this purpose. With all reconstructive surgical techniques and with all autologous replacements there is a risk of reoperation, mainly (besides technical issues) because it is feared that leaving autologous tissue in place leads to recurrence of the original illness. The published results, however, with aortic valve-sparing surgery and with the Ross procedure show that the risk of reoperation appears to be very acceptable. This statement is especially true for the Ross procedure for which more and longer experience exists worldwide. Echocardiographic studies show that the aortic valve function after valve-sparing techniques and - especially - after the Ross procedure is indeed excellent. Therefore, patients with aortic root pathologies or aortic valve diseases should be informed about valve-sparing aortic root reconstructive techniques or the Ross procedure. The choice of technique should be made in close contact between patient, cardiologist, and cardiac surgeon. However, the described techniques require extensive experience within the surgical team. more...

Transannular patching is often performed to relieve congenital pulmonary stenosis, especially in tetralogy of Fallot. Theoretically, a monocusp patch can reduce patch-related pulmonary regurgitation, but the optimal size relation between the implant and the native hypoplastic pulmonary root is not well defined.In 11 pigs, peak pressure gradient and regurgitation fraction across the pulmonary root were measured. During cardiopulmonary bypass, two cusps including the pulmonary artery wall were resected and the midpoint of the free margin of the remaining cusp was sutured to the sinus wall to imitate a hypoplastic pulmonary root. Transannular patching was performed using a noncoronary segment of a porcine aortic root. After discontinuation of cardiopulmonary bypass, all measurements were repeated. Thereafter, the cusp of the patch was resected, and all measurements again repeated. Anatomic dimensions were determined after the pigs had been sacrificed.Regurgitation fraction increased from 0.2% +/- 3.4% at baseline to 15.5% +/- 6.2% after reconstruction with a monocusp patch and to 60.0 +/- 18.6% after the cusp of the monocusp patch had been resected (p0.001). The median peak pressure gradient increased from 0 to 1 to 6 mm Hg (p = 0.013), respectively. The regurgitation fraction negatively correlated with the ratio of the length of the monocusp patch to that of the hypoplastic pulmonary root (r = -0.63, p = 0.037).A monocusp patch for reconstruction of a hypoplastic pulmonary root results in significantly less regurgitation than a nonvalved patch of the same size, while the peak pressure gradient remains normal. The lowest regurgitation fraction was observed with a monocusp patch two-times the length of the circumference of the hypoplastic pulmonary root. more...

Endoaneurysmorrhaphy (EAR) has become an important therapeutic option in the treatment of patients with left ventricular (LV) aneurysm and congestive heart failure. Today, more and more patients are referred for EAR with a dilated akinetic LV rather than a classic dyskinetic LV aneurysm. Little is known about the contribution of the extent of akinesis to perioperative mortality. We reviewed the data of 147 patients with anterior left ventricular aneurysms undergoing EAR. Seventy percent of the patients were male; mean age was 62 9 years. Demographic, hemodynamic, angiographic and surgical variables were analyzed using univariate statistic tests in order to determine risk factors for in-hospital mortality. Eighty-two percent of the LV aneurysms had at least some dyskinesia, but 70% were mainly akinetic. 133 patients had additional bypass surgery, one had additional mitral valve replacement. In-hospital mortality was 4.1% (n=6). Risk factors for in-hospital mortality were the total extent of akinetic myocardium (p=0.027) in the 30degrees RAO view and the duration of cardiopulmonary bypass (CPB, p=0.0068) which was itself dependent on the IV ejection fraction (p=0.001), the number of stenosed coronary arteries (p = 0.004), and the extent of akinesis (p = 0.023). The extent of dyskinesia was not associated with either perioperative mortality (p=0.36) or CPB duration. EAR can be performed with acceptable perioperative results. Because akinesis increases in many patients with time, and because the duration of ECC was dependent on variables reflecting the severity of the underlying heart disease, our findings underscore the importance of optimal timing for the surgical intervention. more...

Background and Objectives During transmyocardial laser revascularization (TMLR), multiple microembolic signals (MES) can be detected in cerebral arteries. We sought to characterize composition and clinical relevance of these MES and to evaluate strategies to reduce cerebral microembolization during TMLR. Study Design/Materials and Methods TMLR was performed in pigs. Laser energy was set to 4–10 J (group A) or 80 J (group B). Oxygen concentration was varied between 21 and 100%. MES were recorded in the ophthalmic artery. Brain and spinal cord were investigated histologically after 10 days. Results More MES could be detected during high- compared to low-energy laser procedures. Ventilation with 100% oxygen reduced the number of MES. No lesions were found on histology. Conclusions The number of MES depends on the laser energy. Laser-induces cavitation-effects lead to an additional release of nitrogen bubbles. Thus, the microembolic load can be reduced by ventilation with 100% oxygen and by decreasing the laser energy. Lasers Surg. Med. 34:379–384, 2004. © 2004 Wiley-Liss, Inc. more...

Introduction: MicroRNAs (miRNAs) are critical regulators of most major cellular processes and seem to play a vital role in the pathogenesis of numerous diseases including atrial fibrillation, the most commonly encountered cardiac rhythm disorder. Among the several miRNAs that appear to be involved in pathogenesis of atrial fibrillation, miRNA 208a is linked to fibrosis and proper cardiac conduction. Methods and Results: By employing whole miRNA microarrays, 30 upregulated und 3 downregulated miRNAs were identified. The validation of the microarrays dataset in 19 left atrial appendage tissue samples (2 paroxysmal, 10 persistent, 7 long-standing persistent) was picked miRNA208, the most differentially expressed one. The relative expression level of miRNA 208a was 2.33 ± 1.99-fold of calibrator in atrial fibrillation tissue, whereas it was 1.4 E−4 ± 2.4 E−4 in RNA obtained from healthy donors control tissue, thus confirming the cardiac specific expression of this miRNA. Atrial fibrillation sub-categories revealed miRNA 208a expression levels of 2.32 ± 2.12 in paroxysmal, 3.26 ± 2.30 in persistent, and 1.14 ± 0.67 in long-standing persistent arrhythmias. The difference in miRNA 208a expression levels between persistent and long-standing persistent atrial fibrillation proved to be significant (p = 0.02). Discussion: The findings from our study suggest a decline in miRNA 208a expression with ongoing arrhythmia, possibly preceded by a rise in expression from paroxysmal to persistent atrial fibrillation or even long-standing persistent. The significant changes in miRNA 208a expression over the course of the disease may be used as an additional diagnostic tool to monitor the progression of atrial fibrillation. more...

Background — As shown previously in goats, clenbuterol increased the power of electrically conditioned skeletal muscle ventricles (SMVs) of clinically relevant size (150 mL), which were constructed around a mock system. They pumped against a pressure of 60 to 70 mm Hg immediately during surgery and up to several months after, finally at >1 L/min. SMVs without clenbuterol administration failed. Thus, we expected that clenbuterol-supported SMVs might become integrated into the circulation by a 1-step operation instead of the 2-step procedure required up to now. Methods and Results — In adult Boer goats (n=5), latissimus dorsi muscle was wrapped around a polyurethane chamber of 150 mL that was connected to the descending aorta. This muscular flow-through pumping chamber containing a stabilizing inner layer (called a biomechanical heart [BMH]) was formed and immediately made to work against a systemic load with the support of clenbuterol (5×150 μg/wk). During surgery, the mean stroke volume of BMHs was 53.8±22.4 mL. One month after surgery, in peripheral arterial pressure, the mean diastolic (P MD ) and minimal diastolic (P min ) pressures of BMH-supported heart cycles differed significantly from unsupported ones (P MD =+2.9±1.1 mm Hg [ P min =−2.4±0.9 mm Hg [ P max , increased by 20.5±8.1% ( P Conclusions — Under support of clenbuterol, BMHs of a clinically relevant size can be trained effectively in the systemic circulation after a 1-step operation and offer the prospect of a sufficient volume shift and probably unloading of the left ventricle. more...

Objective: The clinical benefit in terms of angina reduction after transmyocardial laser revascularization (TMLR) in patients with diffuse coronary artery disease who are not candidates for conventional procedures has been proved. The exact mechanisms of TMLR however, are still unknown. The aim of this study was to investigate the cellular changes in relation to intramyocardial partial oxygen pressure (ptiO2) after TMLR in a model of acute ischemia in pigs by electron microscopical methods (TEM). Methods: Seven pigs were included in this study (five animals with acute myocardial ischemia and additional TMLR and two animals with acute myocardial ischemia and without TMLR for control). Acute ischemia was induced by ligation of diagonal branches of the left anterior descending artery (LAD). Intramyocardial partial oxygen pressure was measured before induction of ischemia and thereafter continuously for up t o6hi n allanimals. Biopsies of all animals were taken before induction of ischemia and thereafter at 30 min, 3 and 6 h. Analysis of the myocardial ultrastructure was focused on mitochondria, cell nucleus, T-tubules and myofibrils. Results: Ultrastructural changes were seen in all animals. At 6 h after induction of ischemia, mitochondria showed a destruction of the internal as well as the external membrane and of the cristae. The nuclei showed margination of the chromatin. Myofibrils were characterized by ruptures in the Z-stripes. Lipid droplets as an indicator of ischemia could be identified. PtiO2 between 40 and 80 mmHg before intervention decreased down to 0‐2 mmHg within the first 9 min after diagonal branch ligation and did not increase even after TMLR. Conclusions: In this acute ischemic model using pigs, TEM evaluation following TMLR proves irreversible changes of the myocardial ultrastructure. Furthermore, TMLR was not able to increase ischemically induced decrease of ptiO2. These data provide some evidence that TMLR thus, may not be able to ameliorate acute ischemia at least in the pig model. Further investigations are needed to investigate the effect of TMLR in chronic myocardial ischemia. © 1997 Elsevier Science B.V. All rights reserved. more...

MicroRNAs (miRNAs) are critical regulators of most major cellular processes and seem to play a vital role in the pathogenesis of numerous diseases including atrial fibrillation, the most commonly encountered cardiac rhythm disorder. Among the several miRNAs that appear to be involved in pathogenesis of atrial fibrillation, miRNA 208a is linked to fibrosis and proper cardiac conduction. We quantified the expression levels of miRNA 208a in left atrial appendage tissue of patients with paroxysmal (n=2), persistent (n=10), and long-standing persistent (n=7) arrhythmia using quantitative PCR. In paroxysmal atrial fibrillation, miRNA 208a was expressed moderately, whereas the expression was enhanced in persistent atrial fibrillation and significantly reduced in long-standing persistent atrial fibrillation. The difference between persistent and long-standing persistent atrial fibrillation was significant at p=0.02. The findings from our study suggest a decline in miRNA 208a expression with ongoing arrhythmia, possibly preceded by a rise in expression from paroxysmal to persistent atrial fibrillation or even long-standing persistent. The significant changes in miRNA 208a expression over the course of the disease may be used as an additional diagnostic tool to monitor the progression of atrial fibrillation. more...

Objective: To assess the impact of a dynamic cardiomyoplasty on failing hearts, it is essential to estimate the contraction force of the skeletal muscle and how its contraction is synchronized with the heart cycle. Methods: In a 6-month study a small fluid-filled, balloon-mounted catheter was placed between the myocardium and the muscular wrap in five adult female Boor goats and two female domestic pigs. The catheter was connected to a subcutaneous measuring chamber whereby pressure monitoring could be accomplished. Distinct pressure signals as a result of function of the dynamic cardiomyoplasty and the heart were detected initially in all animals. Results: Maximal relative pressure from the dynamic cardiomyoplasty was calculated as 336.2% ± 69.4% on day 24 ± 6.1 ( n = 7) and end-stage pressure as 59.8% ± 9.7% on day 174.6 ± 13.1 ( n = 4). A functional loss of pressure signals from the dynamic cardiomyoplasty was correlated to severe histologic muscle damage ( n = 3). Pressure signals transferred from the contracting myocardium to the catheter showed defined segments of contraction, ejection, and filling periods, allowing a mechanical synchronization of the dynamic cardiomyoplasty to the heart cycle. Conclusions: This monitoring catheter enabled the assessment of the functional state of the dynamic cardiomyoplasty and allowed a synchronization to the heart cycle. It will promote understanding and might help to avoid muscle damage in dynamic cardiomyoplasty for an improved outcome of the surgical treatment of end-stage heart failure. (J Thorac Cardiovasc Surg 1997;114:1097-106) more...

Skeletal muscle ventricles used for cardiac assistance were trained dynamically by shifting volume within an elastic training device. To optimize this dynamic training that is by variation of stimulation patterns and application of drugs, methods for stroke volume and energy evaluation were required. A volume shift induced by a muscle contraction resulted in a pressure rise in the training device. Stroke volume was calculated by relating the pressure difference of a muscle contraction to the device's compliance. For validation of the calculated stroke volume, a mock system was built to simulate muscle contractions under various conditions. The stroke volume measured independently and calculated by means of the pressure rise inside the training device, showed an approximately one-to-one relation (R=0.996). Calculation of delivered energy from skeletal muscle ventricles thereby became possible. This method offers a simple, reliable and practical procedure to quantify the dynamic training of skeletal muscle ventricles for use in cardiac assistance. more...

Bicuspid aortic valve (BAV) is the most common congenital cardiac malformation, with an estimated incidence of 1%–2% in the general population. Patients with BAV are predisposed to early and frequent stenosis, regurgitation, and endocarditis, often accompanied by aneurysm and dissection. A family-based genome-wide analysis found that BAV was linked to chromosomal regions 5q, 13q, and 18q, with autosomal dominant inheritance, reduced penetrance and a non-Mendelian inheritance pattern. Mutations in the transmembrane receptor-encoding gene NOTCH1 have been detected in familial and sporadic BAV cases. Mutations in the vascular smooth muscle cell alpha actin gene (ACTA2) have also been identified in BAV patients. Expression of UFD1L, a gene that is highly expressed in the outflow tract during embryogenesis, was downregulated in the cusps of BAV patients compared with those of controls. BAV is associated with left ventricular outflow tract abnormality, including aortic coarctation, arch hypoplasia, and supravalvular and mitral valve stenosis. A male predominance of more than 3:1 has been reported for BAV. This anomaly is very frequent in X0 Turner’s syndrome. Many studies have observed similarities between the histology of aortic aneurysmal tissue in the connective tissue disorder Marfan syndrome (MFS) and the histology of the corresponding tissue in BAV. In this lecture, we review our present understanding of BAV malformation and ascending thoracic aortic aneurysm pathogenesis. We discuss the genetic basis and the basic pathology underlying BAV and aortopathy and compare these with known mechanisms underlying MFS. more...

Aims. Dysregulated expression of the endothelial nitric oxide synthase (eNOS) is observed in aortic aneurysms associated with bicuspid aortic valve (BAV). We determined eNOS protein levels in various areas in ascending aortic aneurysms.Methods and Results. Aneurysmal specimens were collected from 19 patients, 14 with BAV and 5 with tricuspid aortic valve (TAV). ENOS protein levels were measured in the outer curve (convexity), the opposite side (concavity), the distal and above the sinotubular junction (proximal) aneurysm. Cultured aortic cells were treated with NO synthesis inhibitor L-NAME and the amounts of 35 apoptosis-related proteins were determined. In patients with BAV, eNOS levels were significantly lower in the proximal aorta than in the concavity and distal aorta. ENOS protein levels were also lower in the convexity than in the concavity. While the convexity and distal aorta showed similar eNOS protein levels in BAV and TAV patients, levels were higher in TAV proximal aorta. Inhibition of NO synthesis in aneurysmal aortic cells by L-NAME led to a cytosolic increase in the levels of mitochondrial serine protease HTRA2/Omi.Conclusion. ENOS protein levels were varied at different areas of the aneurysmal aorta. The dysregulation of nitric oxide can lead to an increase in proapoptotic HTRA2/Omi. more...

In 2004, a 68-year-old man received aortocoronary bypass surgery and a 23-mm Hancock porcine bioprosthesis (Medtronic, Minneapolis, Minnesota). Six years later, in January 2011, cardiac re-evaluation was performed due to progressive dyspnea. Invasive angiography showed open bypass grafts and severe more...

The bicuspid aortic valve (BAV), the most common congenital cardiac malformation, is associated with ascending thoracic aneurysms and appears to reflect a common developmental defect. (Hahn et al., 1992; Roberts, 1970) The average time of patients with BAV undergoing surgery (of the aortic valve and/or because of complications associated with it) is a decade earlier than patients with a normally developed aortic valve. Accordingly, it is contended that if a diseased BAV must be replaced because of a diseased BAV, the aneurysmal ascending aorta should also be replaced. Valve replacement surgery without replacing the aorta would simplify the surgical intervention and shorten the time of operation. In contrast, an enlarged ascending aorta represents an increased likelihood of the patient undergoing the same surgical procedure after a few years. Replacing the aortic valve in patients with BAV does not prevent the progressive dilation of the aortic root and ascending aorta. (Yasuda et al., 2003) Cellular and extracellular processes are involved in the pathogenesis of the ascending aortic aneurysms in patients with BAV. (Bonderman et al., 1999; Mohamed et al., 2010; Nataatmadja et al., 2003; Tang et al., 2005) Many studies have demonstrated the abnormalities of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in aneurysmal tissues. (Boyum et al., 2004; Koullias et al., 2004; Longo et al., 2002) Using tissue microarray techniques, Koullias et al. detected a significantly higher MMP-2 and MMP-9 levels in BAV compared with normal tricuspid aortic valves (TAV), and even significantly higher MMP-2, MMP-9 and TIMP-1 levels compared with all other tissues (control and TAV together). LeMaire et al. observed a lack of inflammatory processes and an increased MMP-2 level and normal MMP-9, TIMP-1 and TIMP-2 expression levels in aneurysmal tissues obtained from patients with BAV. In contrast, in aneurysmal tissues obtained from patients with TAV, they observed increased inflammatory processes and MMP-9 levels. (Lemaire et al., 2005) Furthermore, they showed an increased incidence of cultured vascular smooth muscle cell (VSMC) loss in BAV and Marfan syndrome (MFS) compared with control samples and suggested that a link between the upregulation of MMP-2 and VSMC apoptosis may exist in MFS. Certainly, there are similarities between the histology of the aneurysmal tissue of the aorta in MFS and that BAV. (Longo et al., 2002) In MFS, a mutation in the gene encoding for the extracellular matrix protein fibrillin-1 can be observed; this mutation leads to dysregulation of the transforming growth factor-beta (TGF-b) signaling. (Dietz et al., 2005) In this chapter, we review the present knowledge for elucidating the ascending aortic aneurysm pathogenesis, particularly in patients with BAV. more...

The aortic valve is a complex structure which functions perfectly in systole and diastole and under a wide range of hemodynamic conditions. Even today, no valve prosthesis can match the function of the native aortic valve. This is — at least partly — due to the fact that the aortic valve is not just an outlet whose cusps do move passively in the blood stream. Rather, the aortic valve — which consists of three cusps attached to the wall of the aortic root — interacts with the aortic root and the left ventricular outflow tract. During the cardiac cycle, the aortic root undergoes complex movements that precede and aide opening and closing of the aortic valve [2, 3, 17, 18]. These complex interactions within the aortic root and throughout the cardiac cycle are not yet completely understood. The aortic valve cusps themselves are thin-walled pocket-like structures, made from specialized tissue with fibrous, elastic, nervous, and muscular properties [13, 16, 21]. No such thin, but at the same time strong and non-thrombogeneic material can be produced in laboratories and even less by industrial processes. more...

The bicuspid aortic valve (BAV) is the most common congenital cardiac malformation. Despite being a seemingly simple and harmless anatomic variation, BAV is said to cause more morbidity than any other congenital cardiac defect [52]. BAV may lead to aortic valve stenosis (AS) or regurgitation (AR), endocarditis, an ascending aortic aneurysm, and/or devastating dissection or rupture. Although these potential consequences of BAV were first described long ago [19, 35, 36], only recently have clinicians become fully aware that the presence of a BAV poses a serious health risk. However, the so-called bicuspid aortic valve syndrome [14] is extremely heterogeneous with some patients having rapidly progressive valve and/or aortic disease, while some individuals with BAV remain free of complications throughout their lifetime. In this article, we review current concepts regarding etiology, pathomechanisms, diagnosis, and treatment of BAV with special emphasis on topics relevant for cardiac surgeons. more...

Background— Twenty-four–hour Holter monitoring (24HM) is commonly used to assess cardiac rhythm after surgical therapy of atrial fibrillation (AF). However, this “snapshot” documentation leaves a considerable diagnostic window and only stores short-time cardiac rhythm episodes. To improve accuracy of rhythm surveillance after surgical ablation therapy and to compare continuous heart rhythm surveillance versus 24HM follow-up intraindividually, we evaluated a novel implantable continuous cardiac rhythm monitoring (IMD) device (Reveal XT 9525). Methods and Results— Forty-five cardiac surgical patients (male 37, mean age 69.7±9.2 years) with a mean preoperative AF duration of 38±45 m were treated with either left atrial epicardial high-intensity focus ultrasound ablation (n=33) or endocardial cryothermy (n=12) in case of concomitant mitral valve surgery. Rhythm control readings were derived simultaneously from 24HM and IMD at 3-month intervals with a total recording of 2021 hours for 24HM and 220 766 hours for IMD. Mean follow-up was 8.30±3.97 m (range 0 to 12 m). Mean postoperative AF burden (time period spent in AF) as indicated by IMD was 37±43%. Sinus rhythm was documented in 53 readings of 24HM, but in only 34 of these instances by the IMD in the time period before 24HM readings (64%, P Conclusion— For “real-life” cardiac rhythm documentation, continuous heart rhythm surveillance instead of any conventional 24HM follow-up strategy is necessary. This is particularly important for further judgment of ablation techniques, devices as well as anticoagulation and antiarrhythmic therapy. more...

Background. For children who require aortic valve replacement, the Ross operation provides a unique advantage of growth potential of the pulmonary autograft in the aortic position. This study assessed the progression of autograft root diameters and its effect on aortic regurgitation (AR). Methods. Neoaortic echo dimensions from 48 children (< 16 years) undergoing Ross operation who had follow-up echocardiograms before age 20 were analyzed (mean follow-up, 5.1 +/- 3.3 years). Results. The mean age at the time of the Ross operation was 10.0 +/- 4.3 years. Mean z values of the neoaortic annulus (1.5 +/- 0.4), sinus (2.5 +/- 0.4), and sinotubular junction (2.6 +/- 0.9) when the autograft was implanted were significantly larger compared with normal values (p < 0.001, all). The mean z values significantly increased with follow-up at the level of the sinus (0.5 +/- 0.1/year, p < 0.001) and the sinotubular junction (0.7 +/- 0.2, p < 0.001), but not at the level of the annulus (0.1 +/- 0.1, p = 0.59). AR increased with follow- up time (0.07 +/- 0.02 grade/year, p < 0.001). AR increased with sinotubular junction diameter (p = 0.028), but there was not significant evidence of an association with annulus diameter (p = 0.25) or sinus diameter (p = 0.40). Conclusions. Children undergoing Ross operation have larger neoaortic root dimensions than healthy children. Growth of the annulus matches somatic growth. The diameters of the sinus and the sinotubular junction increase significantly relative to somatic growth. The latter may explain the development of AR. (Ann Thorac Surg 2009; 88: 594-600) c 2009 by The Society of Thoracic Surgeons more...