H. Reichenspurner

Stanford experience with obliterative bronchiolitis after lung and heart-lung transplantation

BACKGROUNDnObliterative bronchiolitis (OB) is the main chronic complication after heart-lung (HLTx) and lung transplantation (LTx), limiting the long-term success of both transplant procedures.nnnMETHODSnSince 1981, 135 HLTxs and 61 isolated LTxs were performed in 184 patients at Stanford University.nnnRESULTSnThe overall prevalence of OB in patients surviving longer than 3 months postoperatively was 64% after HLTx and 68% after LTx. The actuarial freedom from OB was 72%, 51%, 44%, and 29% at 1, 2, 3, and 5 years, respectively, after HLTx and LTx. An analysis of potential risk factors revealed that the frequency and severity of acute rejection episodes (p < 0.001) and the appearance of lymphocytic bronchiolitis on biopsy (p < 0.05) were significantly associated with the development of OB. With regard to diagnosis of OB, pulmonary function tests show early reductions of the forced expiratory flow between 25% and 75% of the forced vital capacity with subsequent decreases in the forced expiratory volume in 1 second. The sensitivity of transbronchial biopsies has increased to 71% since 1993. Current treatment consists of augmented immunosuppression. Concurrent acute rejection episodes or active OB on biopsy have been treated aggressively with high-dose steroid pulses. Analysis of data from 73 patients with OB after HLTx and LTx revealed actuarial 1-, 3-, 5-, and 10-year survival of 89%, 71%, 44%, and 17% versus 86%, 77%, 63% and 56% in patients without OB (p < 0.05 by log-rank analysis). The main complication and cause of death in patients with OB was superimposed respiratory tract infection, which was treated aggressively.nnnCONCLUSIONSnEarly diagnosis of OB using pulmonary function tests or transbronchial biopsy is possible and important, because immediate treatment initiation has led to acceptable survival rates, with nearly 50% of affected patients still alive 5 years after transplantation. Current experimental research on OB suggests that immune injury is the main pathogenetic event of airway obliteration in animal models; rapamycin and leflunomide are new immunosuppressive agents that may have the potential to prevent and treat airway obliteration.

Obliterative bronchiolitis after lung and heart-lung transplantation

Obliterative bronchiolitis (OB) has emerged as the main cause of morbidity and mortality in the long-term follow-up after lung and heart-lung transplantation. The pathogenesis of OB is multifactorial, with acute rejection and cytomegalovirus infection being the main risk factors for the development of OB. The final common pathway of all inciting events seems to be an alloimmune injury, with subsequent release of immunologic mediators and production of growth factors leading to luminal obliteration and fibrous scarring of the small airways. Analyzing the 14 years of experience in 163 patients at Stanford University, we found a current incidence of bronchiolitis obliterans syndrome or histologically proven OB within the first 3 years after lung and heart-lung transplantation of 36.3%, with an overall prevalence of 58.1% after heart-lung and 51.4% after lung transplantation. Both pulmonary function indices (forced expiratory flow between 25% and 75% of forced vital capacity and forced expiratory volume in 1 second) and transbronchial biopsies have proven helpful in diagnosing bronchiolitis obliterans syndrome or OB at an early stage. Early diagnosis of OB and improved management have achieved survival rates in patients with OB after 1, 3, 5, and 10 years of 83%, 66%, 46%, and 22%, compared with 86%, 83%, 67%, and 67% in patients without OB. Recently, different experimental models have been developed to investigate the cellular and molecular events leading to OB and to evaluate new treatment strategies for this complication, which currently limits the long-term success of heart-lung and lung transplantation.

Analysis of Strengths, Weaknesses, Opportunities, and Threats as a Tool for Translating Evidence into Individualized Medical Strategies (I-SWOT)

BACKGROUNDnIt is the physicians task to translate evidence and guidelines into medical strategies for individual patients. Until today, however, there is no formal tool that is instrumental to perform this translation.nnnMETHODSnWe introduce the analysis of strengths (S) and weaknesses (W) related to therapy with opportunities (O) and threats (T) related to individual patients as a tool to establish an individualized (I) medical strategy (I-SWOT). The I-SWOT matrix identifies four fundamental types of strategy. These comprise SO maximizing strengths and opportunities, WT minimizing weaknesses and threats, WO minimizing weaknesses and maximizing opportunities, and ST maximizing strengths and minimizing threats. Each distinct type of strategy may be considered for individualized medical strategies.nnnRESULTSnWe describe four steps of I-SWOT to establish an individualized medical strategy to treat aortic disease. In the first step, we define the goal of therapy and identify all evidence-based therapeutic options. In a second step, we assess strengths and weaknesses of each therapeutic option in a SW matrix form. In a third step, we assess opportunities and threats related to the individual patient, and in a final step, we use the I-SWOT matrix to establish an individualized medical strategy through matching SW with OT. As an example we present two 30-year-old patients with Marfan syndrome with identical medical history and aortic pathology. As a result of I-SWOT analysis of their individual opportunities and threats, we identified two distinct medical strategies in these patients.nnnCONCLUSIONnI-SWOT is a formal but easy to use tool to translate medical evidence into individualized medical strategies.

Port-access bilateral internal mammary artery grafting for left main coronary artery disease: canine feasibility study.

Abstract Background: To extend the applications of minimal access cardiac surgery, an endovascular cardiopulmonary bypass (CPB) system that allows cardioplegia delivery and cardiac venting was used to perform bilateral internal mammary artery (IMA) bypass grafting in six dogs. Methods: The left IMA (LIMA) was taken down thoracoscopically from three left lateral chest ports, followed by the right IMA (RIMA) from the right side. One left‐sided port was extended medially 5 cm with or without rib resection, to expose the pericardium. Both IMAs were divided and exteriorized through the left anterior mediastinotomy. Flow and pedicle length were satisfactory in all cases. Femoral‐femoral bypass was used and the heart arrested with antegrade delivery of cardioplegic solution via the central lumen of a balloon catheter inflated to occlude the ascending aorta. All anastomoses were made through the mediastinotomy under direct vision. In five studies the RIMA was attached to the left anterior descending artery (LAD) and the LIMA to the circumflex, and in one study the RIMA was tunneled through the transverse sinus to the circumflex and the LIMA was anastomosed to the LAD. All animals were weaned from CPB in sinus rhythm without inotropes. CPB duration was 108 ± 27 minutes (mean ± SD) and the clamp duration was 54 ± 10 minutes. Results: Preoperative and postoperative cardiac outputs were 2.9 ± 0.71/min and 2.4 ± 0.31/min, respectively (p = NS), and corresponding pulmonary artery occlusion pressures were 6 ± 3 mmHg and 7 ± 2 mmHg, respectively (p = NS). All 12 grafts were demonstrated to be fully patent. Postmortem examination revealed well aligned pedicles and correctly grafted target vessels. Conclusion: This canine model demonstrates the potential for a less invasive approach to the surgical management of left main coronary artery disease in humans.

Novel Approaches for BAV Aortopathy Prediction—Is There a Need for Cohort Studies and Biomarkers?

Bicuspid aortic valve (BAV) disease is the most common congenital malformation of the human heart with a prevalence of 1–2% in the general population. More than half of patients with a BAV present with a dilated proximal aorta (so-called bicuspid aortopathy) which is associated with an enhanced risk of life-threatening aortic complications. Up to now, the pathogenesis of bicuspid aortopathy as well as the risk stratification of aortic complications has not yet been sufficiently clarified. Recent findings have shown that bicuspid aortopathy features phenotypic heterogeneity. Two distinct valvulo-aortic phenotypes, the so-called root phenotype, as well as a dilation of the tubular ascending aorta, coincide with a significantly different risk for aortal complications. However, the phenotype-based classification that is only based on these two clinical forms is not sufficient to estimate the risk of aortal complications in a prognostically relevant way. Therefore, there is growing clinical interest to assess novel approaches in BAV research and to introduce circulating biomarkers as an elegant diagnostic tool to improve risk stratification in BAV aortopathy. A large scale epidemiological cohort study, ranking from apparently healthy individuals to disease patients, and comprehensive biobanks provide the opportunity to study BAV disease and its complications and to identify novel biomarkers for BAV aortopathy surveillance and prognosis. Firstly, the data indicate that several protein-based biomarkers and non-coding RNA molecules, in particular circulating microRNAs, can serve as relevant molecular biomarkers to predict the course of BAV-associated aortopathy. Here, we review the current literature and knowledge about BAV from a clinical point of view, and report about novel approaches in BAV biomarker research.

Type A Aortic Dissection with Situs Inversus

A 79-year-old female presented with sudden chest pain and was found to have a dissection flap in the ascending aorta on transthoracic echocardiography (Fig. 1a and b). A contrast-enhanced computer tomogram revealed that the dissection extended from the ascending aorta into the right iliac artery (Fig. 1c). In addition, there was situs inversus with dextrocardia. At the time of surgery, the left axillary artery was cannulated using an 8mm Dacron prosthesis (Gelweave Vascuthek, Ltd., Renfrewshire, UK) and a single-stage venous cannula inserted into the leftsided right atrium. An ascending aorta and hemiarch replacement was performed with a 28mm Dacron Figure 1. (a and b) Computed tomography showing type A aortic dissection; (c) 3D-computed tomography showing situs inversus.

Cardiogenic Shock 14 Years Post Anthracyclines

Significant advances in cancer treatment markedly improved survival rates of children diagnosed with cancer. However, chemotherapeutic or radiologic treatments might result in health consequences. For example, anthracycline agents were one of the most widely used chemotherapeutic drugs and known to cause cardiotoxicity. nWe report on a 20-year old man with sudden onset of multi-organ-failure caused by a severe cardiogenic shock and the urgent need for implantation of a continuous-flow left ventricular assist device. Fourteen years before, he was diagnosed with childhood T-lymphocyte acute lymphoblastic leukaemia implying the application of the ALL-BFM-2000- protocol with a cumulative dose of 240 mg/m2 of anthracycline (120 mg/m2 daunorubicin + 120 mg/m2 doxorubicin). Postchemotherapeutic clinical monitoring lasted for two years till complete remission of leukaemia was diagnosed. Histology of intraoperatively taken endomyocardial biopsies showed an extensive fibrosis and vacuolated cardiomyocytes compatible with late-onset of anthracycline-induced cardiomyopathy. The patient recovered quickly and was discharged to rehabilitation 20 days after continuous-flow left ventricular assist device implant. Our case emphasized the need for consistent and detailed follow-ups to assess the global risk of premature cardiovascular disease prior to the development of congestive heart failure in cancer survivors of the childhood.

Therapie der erweiterten Aorta ascendens: Bikuspide vs. trikuspide Aortopathie

ZusammenfassungHintergrundDie Entwicklung der individualisierten Medizin fordert eine bessere Risikoprädiktion der aortalen Ereignisse und eine differenzierte Behandlung der erweiterten Aorta ascendens.Ziel der ArbeitDer vorliegende Beitrag bietet eine Übersicht zu traditionellen und neuartigen Markern zur Risikoprädiktion der aortalen Ereignisse sowie zur Evidenzlage differenzierter Behandlungskonzepte der bi- vs. trikuspiden Aortopathie.Material und MethodeHierzu wurde die aktuelle Literatur bezüglich der modernen Marker zur Risikoprädiktion der aortalen Komplikationen bei erweiterter Aorta ascendens sowie der differenzierten Behandlungskonzepte der bi- vs. trikuspiden Aortopathie analysiert.ErgebnisseDer maximale Diameter der proximalen Aorta allein ist kein verlässlicher Indikator, um eine Risikostratifikation bezüglich der Aortopathie vorzunehmen; dies gilt insbesondere unter Berücksichtigung der Heterogenität der aortalen Pathologie. Aktuelle Literaturdaten deuten auf das Vorliegen unterschiedlicher Aortopathien innerhalb des Krankheitsbildes der bikuspiden Aortenklappe hin. Diese haben einen unterschiedlichen Ursprung und eine unterschiedliche Prognose und können dadurch eine spezialisierte Behandlungsform erforderlich machen. Basierend auf den Studienergebnissen der letzten Jahre ergeben sich eindeutige Parallelen zwischen der bi- und der trikuspiden Aortopathie, die allerdings bislang noch nicht anhand prospektiver Studien untersucht wurden.SchlussfolgerungenDie individualisierte Risikoanalyse und Therapieentscheidung bei erweiterter Aorta ascendens bedürfen zukünftig der Etablierung von prognostisch-basierten Biomarkern in Kombination mit traditionellen Risikofaktoren.AbstractBackgroundThe development of individualized treatment concepts necessitates better risk prediction models for adverse aortic events and patient-tailored treatment strategies for dilatation of the ascending aorta.ObjectivesThis article provides an overview of traditional and modern markers for risk prediction of adverse aortic events and the state of the art evidence for specific treatment concepts of bicuspid versus tricuspid valve aortopathies.Material and methodsA systematic analysis of the current literature was carried out taking into account the implementation of modern biomarkers for risk prediction of adverse aortic events and differentiated treatment concepts for bicuspid versus tricuspid valve aortopathies.ResultsThe maximum cross-sectional aortic diameter alone is insufficient to provide reliable information for risk stratification with respect to the aortopathy, especially considering the heterogeneous nature of ascending aortic disease. The current literature indicates the presence of marked heterogeneity in the symptoms of diseases of the bicuspid aortic valve, which have different origins and a different prognosis and can therefore necessitate a specialized form of treatment. Based on the study results from recent years there are clear parallels between bicuspid and tricuspid valve aortopathies which, however, have not yet been investigated in prospective studies.ConclusionThe individualized risk analysis and therapy decision-making process for dilatation of the ascending aorta necessitate the future establishment of prognosis-based biomarkers in combination with traditional risk factors.