Armin Welz

Three-dimensional video and robot-assisted port-access mitral valve operation

BACKGROUND In order to minimize surgical trauma, video-assisted mitral valve operation has been started using the Port-Access technique with the addition of a three-dimensional visualization system (Vista Cardiothoracic Systems Inc, Westborough, MA) and a voice-controlled camera-holding robotic arm (Aesop; Computer Motion Inc, Goleta, CA). METHODS Port-Access mitral valve replacement or repair (PAMVR) was undertaken using an endovascular cardiopulmonary bypass (CPB) system. Fifty patients underwent Port-Access mitral valve replacement or repair. A three-dimensional thoracoscope was inserted allowing complete three-dimensional projection of the mitral valve (Vista). In the last 20 patients, the camera was attached to a robotic arm (Aesop), which allowed stabilization and voice-activated movement of the camera. Mitral valve repair was performed in 26 patients, and the valve was replaced in 24 patients with a mechanical valve prosthesis. RESULTS Median time of operation was 4.2 hours, aortic cross-clamp time 83 minutes, CPB time 125 minutes, intensive care unit stay 1.5 days and hospitalization 9.0 days. Three months follow-up was complete in 40 patients, with 34 patients (85%) in New York Heart Association class I and 6 patients in class II. Mortality was 0% and rate of reoperation was 2%, with a follow-up time up to 1.5 years postoperatively. CONCLUSIONS Using three-dimensional video and robotic assistance, it was possible to minimize the length of skin incision, but at the same time to optimally visualize the whole mitral valve apparatus in order to perform true Port-Access mitral valve operation, including various repair techniques.

Resection of hypernephromas with vena caval or right atrial tumor extension using extracorporeal circulation and deep hypothermic circulatory arrest: a multidisciplinary approach.

OBJECTIVE Among retroperitoneal tumors, renal cell carcinoma most often invades the retrohepatic inferior vena cava or the right atrium. Even in these cases, radical nephrectomy may be performed with curative intention. The aim of this retrospective study was to elucidate the impact of cardiopulmonary bypass and hypothermic circulatory arrest on surgical complications, primary mortality, and long-term survival. PATIENTS AND METHODS From Jan. 1981 till Aug. 1996, 44 patients were operated upon for renal cell carcinoma with advanced vena caval extension. The patients were divided into two groups. In 19 cases (Cardiopulmonary Bypass Group), extracorporeal circulation and deep hypothermic circulatory arrest was used. The Conventional Technique Group comprised 25 patients who had radical nephrectomy, paraaortic lymphadenectomy and extirpation of the intracaval tumor thrombus applying common principles in vascular surgery. The median age was 59 years with a range from 42 to 78 years in the Cardiopulmonary Bypass Group, and 60 years, ranging from 22 to 72 years, in the Conventional Technique Group. In addition, both groups did not differ in gender, UICC TNMG staging classification, and perioperative risk factors. A review of the patient charts was done and surveys were sent to survivors or nearest of kin. Wilcoxon test and log-rank test were used as appropriate. RESULTS A lower intraoperative complication rate was found in patients who had surgery using cardiopulmonary bypass. This was especially true with embolization of the tumor thrombus into the pulmonary arteries: 0.0% in Cardiopulmonary Bypass Group and 16.0% in Conventional Technique Group (P < 0.05). Severe hemorrhage occurred in 10.5% (Cardiopulmonary Bypass Group) and 16.0% (Conventional Technique Group). This translated into a significantly lower perioperative mortality in the Cardiopulmonary Bypass Group when compared to the Conventional Technique Group (5.6 and 16.0%, respectively). In spite of these results, differences in long-term survival did not reach statistical significance. But, a trend to superior long-term survival was apparent. The mean survival was 1289 +/- 278 days in the Cardiopulmonary Bypass Group and 746 +/- 166 days in the Conventional Technique Group. CONCLUSIONS Due to acceptable long-term results, the resection of hypernephromas showing extensive vena caval invasion seems to be justified. The use of cardiopulmonary bypass and hypothermic circulatory arrest is able to decrease primary morbidity and mortality. However, the influence on long-term survival remains to be proven.

A post-receptor defect of adenylyl cyclase in severely failing myocardium from children with congenital heart disease.

The aim of this study was to determine whether a defect at the post-receptor level of adenylyl cyclase may also contribute to the decreased effectiveness of cAMP-increasing agents in severely failing patients with congenital heart disease. The severity of congestive heart failure in 31 patients with congenital heart disease was graded by a scoring system which included a description of historical and clinical variables. Patients were divided into a group with no or mild heart failure (score < or = 6) and a group with severe heart failure (score > 6). beta-Adrenoceptor-stimulated adenylyl cyclase activity was significantly decreased by 65% in patients with severe heart failure in comparison to the group of patients with no or mild heart failure. In addition, receptor-independent adenylyl cyclase stimulation by forskolin was reduced by 52% in patients with score > 6 compared to patients with score < or = 6. This post-receptor defect of adenylyl cyclase was apparently due to a decrease in the activity of catalytic subunit of adenylyl cyclase as adenylyl cyclase stimulation by forskolin in the presence of Mn2+ which uncouples catalytic subunit from the G proteins, G(s) and G(i), was also significantly diminished in the patients with severe heart failure. In contrast, the level of inhibitory G protein alpha-subunits was apparently not different in the two groups. In summary, the data indicate that a defect at the catalytic subunit of adenylyl cyclase apparently contributes to the decreased effectiveness of cAMP-increasing agents in severely failing patients with congenital heart disease.

Long-term prognosis of surgically-treated aortic aneurysms and dissections in patients with and without Marfan syndrome

OBJECTIVE Aortic aneurysms and dissections are the leading causes of premature death in Marfan syndrome (MfS). This study aims to compare long-term results of surgically treated aortic aneurysms and dissections in patients with and without MfS in respect to early and late prognosis. METHODS From March 1975 to August 1994, 33 patients with classic MfS (group A, age 34.2 +/- 9 years) and 298 patients with non-fibrillinopathic aortic disease (group B, age 54 +/- 13 years) underwent aortic surgery. Acute dissections occurred in 57.6 (A) versus 37.9% (B). A total of 54.6% of patients in group A were treated with a composite graft versus 16.4% in B. The aortic arch and the descending aorta was replaced in 30.4% of MfS patients and 24.9% of patients without MfS. RESULTS We observed 7 (25.0%, A) versus 35 (14.2%, B) late deaths among the 28 (A) versus 247 (B) early survivors. In 5 patients (17.9%) of A and 8 patients (3.2%) of B, late death was caused by redissection or recurrent aneurysm (P < 0.001). Long-term survival after 5, 10 and 15 years in group A was 82 +/- 7, 60 +/- 11 and 30 +/- 22%, and 75 +/- 3, 69 +/- 3 and 64 +/- 4% in group B. A total of 22 reoperations were performed in 11 MfS patients, 17 reoperations were due to recurrent aortic diseases. Three of the 8 patients underwent reoperation after Wheat procedure because of sinus valsalva aneurysm. None of the patients with composite graft replacement needed reoperation in this segment, but 3 patients suffered from redissection at the proximal aortic arch. In group B, reoperations were significantly less frequent (10.7%) compared to MfS patients (66.7%; P < 0.001). CONCLUSIONS Surgical treatment of aortic disease in MfS patients is associated with a high risk of redissection and recurrent aneurysm. If the ascending aorta needs to be replaced, we recommend the composite graft technique and a more aggressive approach to reduce the frequency of distal reoperations. In order to reduce the high reoperation rate in MfS patients, frequent clinical follow-up may contribute to improve life expectancy in MfS patients.

Is cardiac surgery justified in patients in the ninth decade of life

Abstract  Background: Due to aging of the population the upper‐age limit for cardiac operations has constantly been extended. In the current era of health care reform the ability to provide appropriate care for geriatric patients at acceptable costs is a major individual and societal concern. The objective of this study was to evaluate the results of cardiac surgery in octogenarians regarding overall morbidity and mortality as well as to quality of life. Methods: Between February 1992 and August 1995,101 consecutive octogenarians underwent several types of cardiac operations. Operative procedures consisted of coronary artery bypass grafting (CABG) in 45 patients, valve replacement or repair in 33 patients, and combined CABG and combined procedures in 19 patients. All surviving patients were mailed a questionnaire 3 to 62 months (22.1 ± 15.4 months) postoperatively concerning the postoperative course and quality of life (97.5% follow‐up). Results: The early mortality was 15.5% in the CABG group, 3.0% in the valve group, and 21.7% in the combined procedure group; 5‐year actuarial survival was 79.1% in the CABG group, 86.9% in the valve group, and 58.8% in the combined procedure group, respectively. The questionnaire sent to the survivors revealed that 81.0% of patients considered their functional status better or much better than before surgery. Of the survivors, 97.3% stated that according to their opinion the operation was worthwhile. Conclusion: Cardiac surgery is justified for carefully selected patients in the ninth decade of life. Although these patients are at increased risk of operative death and surgical complications compared with younger patients, the majority regain a life expectancy in the range of that of the global population. Furthermore, they are presented the chance to retain or maintain an independent lifestyle.

Switch from a BIVAD to a LVAD in a boy with Kawasaki disease.

A 9-year-old boy with Kawasaki disease survived after two severe myocardial infarctions. Thereafter pharmacologically untreatable ventricular arrhythmia and rapidly deteriorating heart failure developed in the patient. After 19 days of biventricular and a further 27 days of left univentricular mechanical circulatory support with the Berlin Heart (Cardiotechnica, Berlin, Germany) assist device the boy successfully underwent heart transplantation. At a follow-up of 54 months, the boy is leading an active and unrestricted life.

A novel mutation in the neonatal region of the fibrillin (FBN) 1 gene associated with a classical phenotype of Marfan syndrome (MfS)

Marfan Syndrome (MfS) is an autosomal dominant inherited connective tissue disorder with variable phenotypic expression of cardiovascular, skeletal and ocular manifestations. Cardiovascular complications, such as aortic aneurysm and dissection drastically reduce life expectancy of individuals with MfS, whereas preventive surgery substantially improves the prognosis of these patients. A number of mutations in the fibrillin 1 (FBN1) gene associated with MfS have been identified to date, demonstrating considerable molecular heterogeneity. One region, however, located around exon 24, exhibits a striking clustering of mutations, which are associated with a severe, socalled neonatal form of MfS. Here we report the first mutation (G2950A) in exon 24 of the neonatal region of the FBN1 gene, associated with a classic MfS phenotype. The mutation leads to the substitution of valin by isoleucin (V984I), both uncharged amino acids, which only differ in a single methyl group. This defect was identified in a proband with cardiovascular manifestations of MfS by SSCP analysis of PCR‐amplified genomic DNA, direct PCR sequencing and RFLP analysis. The substitution was neither detected in the unaffected 4‐year old daughter of the proband, nor in 3 of his healthy family members nor in 108 allels from control individuals, suggesting that this mutation is causative for MfS in the patient. Since no other family member of the proband is affected by MfS, the defect described is sporadic. In summary, we identified a novel defect in exon 24 of the neonatal region of the FBN1 gene in a patient with a classic phenotype of MfS, suggesting that conservative substitutions in this region may lead to a less severe phenotype of the disease. This finding further demonstrates the remarkable phenotypic heterogeneity associated with FBN1 mutations and stresses the significance of modifying genes and individual alterations in protein function for the phenotypic expression of the disease. Hum Mutat 12:137, 1998.

Minimal-invasive Herzchirurgie – eine Modeerscheinung oder ein klinisch anerkanntes Therapieverfahren?

In den letzten 5 Jahren sind im Bereich der Herzchirurgie neue, weniger invasive Operationsverfahren entwickelt worden, die unter dem Oberbegriff minimal-invasive Herzchirurgie zusammengefaßt werden. Man unterscheidet dabei Verfahren, die auf die Anwendung der extrakorporalen Zirkulation verzichten und in erster Linie in der Koronarchirurgie zum Einsatz kommen (sogenannte minimal-invasive direkte koronare Bypasschirurgie oder MIDCAB-Verfahren). Diese Operation kann entweder über eine kleine Thorakotomie oder über eine volle Sternotomie vorgenommen werden. Demgegenüber gibt es Operationstechniken, bei denen über einen limitierten Zugang ein endovaskuläres Bypass-System zum Einsatz kommt und ein Abklemmen der Aorta ascendens mit Gabe von kardiopleger Lösung möglich ist (sogenannte Port-Access-Technik). Auch in der Klappenchirurgie sind in den letzten Jahren verschiedene Operationsverfahren entwickelt worden, welche den Zugang zur Herzklappe über eine limitierte Sternotomie oder kleine Thorakotomie ermöglichen. In der Chirurgie kongenitaler Vitien sind ebenfalls weniger invasive Operationsverfahren zum Einsatz gekommen. Dieser Artikel soll nun die einzelnen Operationsverfahren näher beschreiben und die Indikationen für diese Eingriffe definieren. Within the last 5 years new less invasive surgical techniques have been developed in the field of cardiac surgery. This new field named minimally invasive cardiac surgery can be subdivided into techniques which do not require cardiopulmonary bypass and are used mainly for coronary artery surgery (called minimally invasive direct coronary artery surgery, MIDCAB technique). This MIDCAB procedure can be done through a small left anterior thoracotomy or a sternotomy. In addition there are other methods which allow the performance of complex cardiac surgery through small accesses in combination with the use of an endovascular CPB system and internal aortic clamping to achieve cardioplegic arrest (so-called Port-Access method). Also for valvular surgery, new surgical techniques were developed allowing access to mitral and aortic valves through limited incisions. In addition, new less invasive techniques were developed for congenital heart surgery. This article will describe the various surgical techniques and define the indications for minimally invasive cardiac surgery.

A novel mutation in the neonatal region of the fibrillin (FBN)1 gene associated with a classical phenotype of Marfan syndrome (MfS). Mutations in brief no. 163. Online.

Hereditary hemmorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by multisystemic vascular dyplasia and recurrent hemorrhage. One of the causative genes is the activin receptor-like kinase-1 (ALK-1) gene located on chromosome 12q13. ALK-1 is an endothelial cell type I receptor for the TGF-beta superfamily of ligands. As a number of mutations have been identified in the kinase domain of ALK-1, we initiated a mutation analysis specifically targeting the first four coding exons of ALK-1 in order to determine if mutations in the extracellular and transmembrane domains are also present in HHT. Six new mutations have been identified. Three frameshift mutations were identified in exons encoding the extracellular and transmembrane domains. These mutations would grossly truncate the ALK-1 protein and are thus classic null alleles. Three new missense mutations within the exons encoding the extracellular domain, in addition to two previously described missense mutations, are located at or near highly conserved cysteines. These mutations may disrupt intra- or inter-molecular disulfide bridges required for ligand binding. The combined data suggest that both severe and subtle changes in the ALK-1 amino acid sequence can lead to receptor dysfunction and result in the HHT disease phenotype.Marfan Syndrome (MfS) is an autosomal dominant inherited connective tissue disorder with variable phenotypic expression of cardiovascular, skeletal and ocular manifestations. Cardiovascular complications, such as aortic aneurysm and dissection drastically reduce life expectancy of individuals with MfS, whereas preventive surgery substantially improves the prognosis of these patients. A number of mutations in the fibrillin 1 (FBN1) gene associated with MfS have been identified to date, demonstrating considerable molecular heterogeneity. One region, however, located around exon 24, exhibits a striking clustering of mutations, which are associated with a severe, socalled neonatal form of MfS. Here we report the first mutation (G2950A) in exon 24 of the neonatal region of the FBN1 gene, associated with a classic MfS phenotype. The mutation leads to the subsitution of valin by isoleucin (V984I), both uncharged amino acids, which only differ in a single methyl group. This defect was identified in a proband with cardiovascular manifestations of MfS by SSCP analysis of PCR-amplified genomic DNA, direct PCR sequencing and RFLP analysis. The substitution was neither detected in the unaffected 4-year old daughter of the proband, nor in 3 of his healthy family members nor in 108 allels from control individuals, suggesting that this mutation is causative for MfS in the patient. Since no other family member of the proband is affected by MfS, the defect described is sporadic. In summary, we identified a novel defect in exon 24 of the neonatal region of the FBN1 gene in a patient with a classic phenotype of MfS, suggesting that conservative substitutions in this region may lead to a less severe phenotype of the disease. This finding further demonstrates the remarkable phenotypic heterogeneity associated with FBN1 mutations and stresses the significance of modifying genes and individual alterations in protein function for the pheontypic expression of the disease.Nephrogenic diabetes insipidus (NDI) is a rare, mostly X‐linked recessive disorder characterized by renal tubular resistance to the antidiuretic effect of arginine vasopressin. The gene responsible for the X‐linked NDI, the G‐protein‐coupled vasopressin V2 receptor, has been localized on the Xq28 region. In this study we present three NDI families from Hungary with three different missense mutations in the vasopressin V2 receptor gene. After the mutations in the affected probands in each family had been characterized, other family members were screened by restriction enzyme analysis. The N317K and the W323S mutations have not been detected previously. The C112R is an already known mutation. The N317K was a de novo mutation in the patient. The C112R and the W323S were found in the mothers of the patients as carriers and in all other patients, but not in the unaffected members of the families. Segregation of the mutations was consistent with the clinically observed symptoms as well as their severity. As conclusion, these findings provide further evidence that X‐linked NDI results from defects in the V2 receptor gene. Hum Mutat 12:137–138, 1998.

Operative Behandlung der Mitralklappeninsuffizienz

Die Mitralklappeninsuffizienz ist ein häufiges Vitium. Liegt eine bakterielle Endokarditis als Ursache vor, kann ein vorgezogener operativer Eingriff indiziert sein. Neben dem Rückgang des mechanischen Klappenersatzes wird eine weitere Zunahme der Mitralklappenrekonstruktionen verzeichnet, der Zugang zum Herzen gelingt zunehmend minimalinvasiv. Dieser Trend setzt sich fort mit der Entwicklung von Operationsverfahren am schlagenden Herzen.