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Hans H Sievers

Publications and source records attributed to Hans H Sievers.

13 recordsLinked to original sources
PubMed2006

A critical reappraisal of the Ross operation: renaissance of the subcoronary implantation technique?

BACKGROUND: The autograft procedure, an option in aortic valve replacement, has undergone technical evolution. A considerable debate about the most favorable surgical technique in the Ross operation is still ongoing. Originally described as a subcoronary implant, the full root replacement technique is now the most commonly used technique to perform the Ross principle. METHODS AND RESULTS: Between June of 1994 and June of 2005, the original subcoronary autograft technique was performed in 347 patients. Preoperative, perioperative, and follow-up data were collected and analyzed. Mean patient age at implantation was 44+/-13 years (range 14 to 71 years; 273 male, 74 female). Bicuspid valve morphology was present in 67%. The underlying valve disease was aortic regurgitation in 111 patients, stenosis in 46 patients, combined lesion in 188 patients, and active endocarditis in 22 patients (in 2 patients without stenosis or regurgitation). Concomitant procedures were performed in 130 patients. Clinical and echocardiographic follow-up visits were obtained annually (mean follow up 3.9+/-2.7 years, 1324 patient-years; completeness of follow-up 99.4%). The in-hospital mortality rate was 0.6% (n =2), and the late mortality was 1.7% (n=6), with 5 noncardiac deaths (4 cancer, 1 multiorgan failure after noncardiac surgery) and 1 cardiac death (sudden death). At last follow-up, 94% of the surviving patients were in New York Heart Association class I. Ross procedure-related valvular reoperations were necessary in 9 patients: Three received autograft explants, 5 received homograft explants, and 1 received a combined auto- and homograft explant. At last follow-up visit, autograft/homograft regurgitation grade II was present in 5/10 patients and grade III in 4/0. Maximum/mean pressure gradients were 7.4+/-6.2/3.7+/-2.1 mm Hg across the autograft and 15.3+/-9.4/7.6+/-5.0 mm Hg across the right ventricular outflow tract, respectively. Aortic root dilatation was not observed. Freedom from any valve-related intervention was 95% at 8 years (95% confidence interval 91% to 99%). CONCLUSIONS: Midterm follow-up of autograft procedures according to the original Ross subcoronary approach proves excellent clinical and hemodynamic results, with no considerable reoperation rates. Revival of the original subcoronary Ross operation should be taken into account when considering the best way to install the Ross principle.

Adolescent↗
PubMed2006

Novel missense mutations (p.T596M and p.P1797H) in NOTCH1 in patients with bicuspid aortic valve.

The bicuspid aortic valve (BAV) is the most common congenital cardiac malformation, occurring in 1-2% of the population. In a recent report, mutations in NOTCH1 a signaling and transcriptional regulator have been shown to cause BAV in two families. This study provides data on systematic sequencing in search for novel mutations in NOTCH1 gene in a large sample BAV. For the first time, we report results of a systematic mutation-analysis based on DNA-sequencing of all coding exons and adjacent splice consensus sequences of NOTCH1 gene. Our analyses revealed 57 NOTCH1 sequence variants. Twenty-one variants are located within exons and 36 within intronic or 5'-UTR sequences. Thirty-five variants were described previously as polymorphisms. The remaining 22, however, were neither listed in public SNP databases nor in the literature and were therefore considered novel. Seventeen variants were found only once (MAF = 1%), of these 15 were novel. Two sequence variants led to amino acid substitutions (p.T596M and p.P1797H) and are located in highly conserved regions of the NOTCH1 protein. In addition, these two mutations could not be detected in at least 327 healthy controls by using RFLP-analysis. The functional relevance of the other 13 novel and rare variants could not be proven without further functional examination. In this study, we provide a new evidence that the mutations in the NOTCH1 gene may trigger the underlying mechanism causing the valve calcification, especially in BAV. In conclusion, NOTCH1 gene mutations do not only play a role in familiar BAV, but can also be observed in approximately 4% of sporadic cases.

Adult↗
PubMed2006

Mitochondrial DNA deletions and the aging heart.

Mitochondrial DNA (mtDNA) mutations appear to be associated with a wide spectrum of human disorders and proposed to be a potential contributor of aging. However, in an age-dependent increase of the common 4977 bp deletion of human mtDNA still many unanswered questions remain. Comparing mtDNA copy levels in different tissues revealed that cardiac muscle had the highest, while the cortex cerebelli showed the lowest copy number of mtDNA in every donor. Intriguingly, mtDNA copy number showed no changes during aging. In heart tissue, the amount of 4977 bp mtDNA deletion increased in an age-dependent manner showing significant differences at the age of 40 years and older (p<0.005). In vitro studies analyzing human normal cells transfected with telomerase (BJ-T) revealed that oxidative stress (OS)--a well accepted promoter of aging--induced 4977 bp deletion and point mutations as demonstrated by real-time PCR and DHPLC analysis. Interestingly, OS induced apoptosis only in transformed human fibroblasts by activation of the intrinsic (mitochondrial-mediated) signalling pathway as indicated by morphological damage of mitochondria, DNA laddering and increase of the Bax/Bcl-2 ratio. In conclusion, in heart tissue, the amount of the 4977 bp deletion increased in an age-dependent manner and it was more detectable after the 4th decade of life, although there was some scatter in the data. Since, apoptosis was induced by the mitochondria-mediated pathway only in transformed cells, the role for apoptosis in normal tissue of the aging heart remains unclear.

Adolescent↗
PubMed2005

Surgical closure of the left atrial appendage - a beneficial procedure?

BACKGROUND: Closure of the fibrillating left atrial appendage (LAA) has been recommended during valve surgery to decrease the risk of arterial embolism. However, patients undergoing surgical LAA closure have not systematically been reevaluated for complete LAA obliteration. METHODS AND RESULTS: During a 12-month period, we studied 6 consecutive patients with paroxysmal (n = 3) or permanent (n = 3) atrial fibrillation who underwent surgical LAA closure at the time of valve surgery. Transesophageal echocardiography (TEE) performed 23-159 days (mean 51) postoperatively demonstrated complete LAA closure in only 1 patient. In 5 patients, incomplete LAA closure was found due to disruption of the closure line. The size of the residual LAA orifice ranged from 3 to 20 mm. There was a high flow velocity at the LAA orifice (0.33-2.2 m/s), whereas flow in the LAA body was low (<0.2 m/s). Spontaneous echocardiographic contrast (SEC) in the LAA had newly developed (n = 3) or was much more intense than preoperatively (n = 2). Despite therapeutic anticoagulation 2 patients showed a LAA thrombus which had not been present on the preoperative TEE, and 1 patient with SEC suffered a stroke 4 weeks after attempted LAA closure. CONCLUSION: Surgical LAA closure was incomplete in most patients, resulting in blood stagnation and an increased likelihood of clot formation. Incomplete surgical LAA closure, therefore, may promote rather than reduce the risk of stroke. Intraoperative TEE is mandatory to verify complete LAA obliteration.

Aged↗
PubMed2005

Optimal size of a monocusp patch for reconstruction of a hypoplastic pulmonary root: an experimental study in pigs.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (p < 0.001). 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). CONCLUSIONS: 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.

Animals↗
PubMed2004

Cardiac troponin T for prediction of short- and long-term morbidity and mortality after elective open heart surgery.

BACKGROUND: Increased cardiac troponins in blood are observed after virtually every open heart surgery, indicating perioperative myocardial cell injury. We sought to determine the optimum time point for blood sampling and the respective cutoff value of cardiac troponin T (cTnT) for risk assessment in patients undergoing cardiac surgery. METHODS: In a series of 204 patients undergoing scheduled open heart surgery, mainly for coronary artery bypass grafting (n = 132) or valve repair (n = 27), cTnT concentrations were measured before and 4 and 8 h after cross-clamping and then daily for 7 days. Individual risk was assessed by use of the Cleveland Clinic Foundation Risk score and intraoperative risk indicators such as duration of cardiopulmonary bypass, cross-clamping, and perioperative release of cardiac markers. Patients were followed for 28 months. RESULTS: Cardiac mortality, all-cause mortality rates, and rates of nonfatal acute myocardial infarction (AMI) at 28 months were 6.9%, 8.8%, and 6.8%, respectively. cTnT was higher in patients with Q-wave AMI or postoperative heart failure requiring inotropic support, and in nonsurvivors. The ROC curve revealed a cTnT > or = 0.46 microg/L at 48 h as the optimum discriminator for long-term cardiac mortality. Stepwise logistic regression identified higher Cleveland Clinic Risk Score [odds ratio (OR) = 2.6 per point], cross-clamp time >65 min (OR = 6.6), and cTnT (OR = 4.9) as significant and independent predictors of long-term cardiac mortality. CONCLUSIONS: A single postoperative cTnT measurement can be used to estimate myocardial cell injury that impacts long-term survival after open heart surgery. It adds independently to established risk indicators.

Aged↗
PubMed2004

Strategies for the reduction of cerebral microembolism during transmyocardial laser revascularization.

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.

Animals↗
PubMed2004

Significant damage of the conduction system during cardioplegic arrest is due to necrosis not apoptosis.

OBJECTIVES: Ventricular conduction disturbances following cardioplegic arrest remains a serious, yet unsolved problem. In the present study we examined whether myocardial conduction cells (MCC, Purkinje fibers) are more vulnerable to ischemia/reperfusion injury than working myocardial cells and whether the damage is due to necrosis or apoptosis. METHODS: Mini-pigs were subjected to 60 min of crystalloid (St Thomas; n = 15 group I) or blood (Buckberg; n = 6 group II) cardioplegic arrest followed by 3 h of reperfusion. Animals not subjected to either procedures served as controls (n = 5). Ventricular myocardial specimens were investigated by hematoxylin and eosin (HE) and periodic acid Schiff (PAS) staining and immunohistochemical labeling of apoptosis-associated proteins (Bax, Bcl-2, Caspase-3). DNA-breaks were visualized by in situ end labeling (terminal deoxynucleotidyl transferase dUTP-biotin nick-end labeling, TUNEL). Electron microscopy confirmed apoptosis or necrosis. RESULTS: MCC of control hearts intrinsically expressed Bax, Bcl-2, and Caspase-3 without signs of either apoptotic or necrotic damage. Subendocardial Purkinje fibers of groups I and II hearts exhibited focal damage, with reduced labeling of apoptosis-associated proteins, glycogen loss, karyopycnosis and increased eosinophilia (15/21 hearts). The majority of damaged MCC displayed nuclear TUNEL-positivity (2.8+/-2.5% of MCC), whereas the average TUNEL-rate of the adjacent working myocardium was low (<0.1%). Electron microscopy demonstrated ischemic changes in MCC consistent with cellular necrosis. CONCLUSIONS: Ischemia/reperfusion injury due to cardioplegic arrest inflicts significant damage on subendocardial MCC, but not on working myocardium. Ultrastructural and light-microscopic findings are consistent with coagulation necrosis, rather than apoptosis.

Animals↗
PubMed2004

Hemodynamic performance following the Ross operation: comparison of two different techniques.

BACKGROUND AND AIM OF THE STUDY: The Ross operation as aortic valve replacement has undergone technical evolution. Originally described as a subcoronary implant, the full-root replacement technique is now more common worldwide. It remains unclear which of the two techniques has the better results. Hence, the hemodynamic performances of the two implantation methods, as applied by two experienced centers, were compared as part of the German Ross Registry. METHODS: In total, 132 (Group 1, root replacement, mean age 40 +/- 14 years) and 249 (Group 2, subcoronary implant, mean age 48 +/- 14 years) consecutively operated patients were compared clinically and echocardiographically. Data were analyzed focusing on pulmonary autograft and homograft function at mid-term (2.78 +/- 1.89 versus 2.26 +/- 2.11 years). RESULTS: Echocardiography revealed autograft peak systolic gradients of 5.0 +/- 2.7 mmHg for Group 1 and 6.7 +/- 3.7 mmHg for Group 2 (p < 0.05), and an indexed effective orifice area (EOA) of 1.98 +/- 0.57 cm2/m2 and 1.64 +/- 0.43 cm2/m2 (p < 0.05), respectively. Homograft peak systolic gradients were 15.6 +/- 9.0 mmHg and 11.7 +/- 6.8 mmHg for Groups 1 and 2 (p < 0.05) respectively, and the indexed EOA with regard to the homograft was 1.08 +/- 0.49 cm2/m2 and 1.26 +/- 0.50 cm2/m2 (p < 0.05). Autograft insufficiency grade > I was present in 1.5% (2/132) of Group 1 and 2.8% (7/249) of Group 2 patients. Pulmonary insufficiency grade > I was 17.4% (23/132) for Group 1 and 4.8% (12/249) for Group 2 (p < 0.05). CONCLUSION: Although both groups enjoyed excellent hemodynamics in the mid-term, the root replacement technique had the advantage of larger annulus diameters and greater aortic EOA. Clinically relevant autograft regurgitation in both groups was gratifyingly rare, and seemed to be independent of surgical technique. Long-term durability of the more demanding subcoronary technique versus the problems of larger dimensions of the sinus of Valsalva and sinotubular junction in the free-root technique, remains to be proven. Apparent differences in pulmonary homograft hemodynamics can most likely be explained by surgical differences, younger patients in Group 1, and by homograft variation.

Adult↗
PubMed2003

Up to 7 years' experience with valve-sparing aortic root remodeling/reimplantation for acute type A dissection.

BACKGROUND: Aortic valve-sparing operations for acute type A dissection are appealing and innovative but less well defined surgical techniques requiring further evaluation. METHODS: We reviewed all consecutive patients with acute type A dissection who underwent either the remodeling (group 1, n = 21) or the reimplantation valve-sparing technique (group 2, n = 15) since October 1994. Patients were followed up clinically and echocardiographically for as long as 41.3 months (group 1) and 87 months (group 2). RESULTS: Hospital mortality was 19% (n = 4) for group 1 and 20% (n = 3) for group 2. Permanent new neurologic symptomatology occurred in 1 patient (3.6%). Three patients in group 1 required reoperation owing to redissection. No patient had an aortic insufficiency of more than grade 1. No late neurologic or thrombembolic events occurred. There was no statistically significant difference between both groups with respect to clinical and hemodynamic data. CONCLUSIONS: Remodeling and reimplantation aortic valve-preserving operations in acute type A dissection can be performed with adequate perioperative risk and excellent midterm aortic valve function. We found no evidence of one technique being superior to the other, however durability of the remodeling technique needs critical consideration especially in Marfan syndrome and when glue is used.

Acute Disease↗
PubMed2002

[Status of aortic valve reconstruction and Ross operation in aortic valve diseases].

BACKGROUND: At first glance the aortic valve is a relative simple valve mechanism connecting the left ventricle and the ascending aorta. Detailed analysis of the different components of the aortic valve including the leaflets and sinuses revealed a complex motion of each part leading to a perfect durable valve mechanism at rest and during exercise. Theoretically, the reconstruction or imitation of these structures in patients with aortic valve disease should lead to optimal results. Prerequisite is the exact knowledge of the important functional characteristics of the aortic valve. The dynamic behavior of the aortic root closely harmonizing with the leaflets not only warrants stress minimizing and valve durability, but also optimizes coronary flow, left ventricular function and aortic impedance. The newly discovered contractile capacity of the leaflets and the root components are important for tuning the dynamics. AORTIC VALVE RECONSTRUCTION: Isolated reconstruction of the aortic valve such as decalcification, commissurotomy, plication of ring or leaflets of a tricuspid aortic valve and cusp extension are seldom indicated in contrast to the reconstruction of the bicuspid insufficient valve. Proper indication and skilled techniques lead to excellent hemodynamic and clinical intermediate-term result up to 7 years after reconstruction. Latest follow-up revealed a mean aortic insufficiency of 0.7, maximal pressure gradient of 11.4 +/- 8.5 mm Hg with zero hospital or late mortality, reoperation or thromboembolic events in 22 patients. The reconstructive techniques for aortic root aneurysm and/or type A dissection according to David or Yacoub have become routine procedures in the last 10 years. The hemodynamic and clinical results are excellent with low reoperation rate and very low risk of thromboembolism. Generally, a maximal diameter of the root of 5 cm is indicative for performing the operation. In patients with Marfan's syndrome the reconstruction should be advanced even with smaller diameters especially if these are progressive and combined with aortic insufficiency. ROSS-OPERATION: The Ross-Operation includes the replacement of the diseased aortic valve with the pulmonary autograft and reconstruction of the right ventricular outflow tract using a homograft. The hemodynamic results are excellent regarding the autograft and also the clinical results with very low thromboembolic risk and acceptable reoperation rate. This method is especially indicated for active young patients, women, who desire children, athletes and patients in general, who like to avoid long-term anticoagulation. In some cases the homograft may develop a dysfunction predominantly a pulmonary stenosis requiring reoperation. In the author's series of 245 Ross-operations in 12 years the homograft had to be replaced in 4 cases without letality. Innovative, decellularized homografts with the potential to repopulate with autologeous cells show promising results after 1 year of clinical implantation without signs of antibody development. Probably these tissue-engineered modification may improve the homograft results. The reconstructive techniques of the aortic valve and the Ross-operation have a certain risk of reoperation that must be weighed against the advantages of very low hospital and late valve related death, excellent hemodynamics, very low risk of macro- and microembolism as well as bleeding, lack of long-term anticoagulation and unrestricted life-style.

Adult↗