I. Aleksic

Different Effects of Thrombin Receptor Activation on Endothelium and Smooth Muscle Cells of Human Coronary Bypass Vessels Implications for Venous Bypass Graft Failure

BACKGROUND Thrombin is implicated in coronary bypass graft disease; it cleaves its receptors extracellular N-terminal domain and unmasks a new N-terminus as a tethered ligand. We studied the effects of thrombin receptor activation in human internal mammary artery (IMA) and saphenous vein (SV). METHODS AND RESULTS To study the effects of thrombin receptor activation on vasomotion, isolated blood vessels were suspended for isometric tension recording, and the effects on cell proliferation were studied in cultured smooth muscle cells (SMCs) of IMA and SV. Thrombin receptor expression in IMA and SV was analyzed by reverse transcription polymerase chain reaction and immunohistology. Receptor function was studied by analyzing the activation of mitogen-activated protein kinase (p42MAPK). In IMA thrombin evoked endothelium-dependent relaxations (65 +/- 5%) that were mimicked by thrombin receptor agonist peptide (TRAP) and reduced by the thrombin inhibitors recombinant (r-) hirudin and D-Phe-Pro-Arg-chloromethyl ketone (PPACK) (P < .05). In SV thrombin caused contractions (36 +/- 5% of 100 mmol/L KCl) that were inhibited by r-hirudin or PPACK (P < .05) but not mimicked by TRAP. In SMCs thrombin induced more pronounced [3H]thymidine incorporation (inhibited by r-hirudin or PPACK) in SV than IMA (P < .05), but activation of p42MAPK was similar in both vessels. TRAP induced weaker activation of p42MAPK than thrombin and did not stimulate [3H]thymidine incorporation in SMCs of SV or IMA. Immunohistology and RT-PCR demonstrated that the endothelium and SMCs of IMA and SV express thrombin receptor. CONCLUSIONS Functional thrombin receptors are present on endothelium and SMCs of IMA and SV. Endothelial thrombin receptors mediate relaxation in IMA but not SV. Thrombin causes much more pronounced contraction and proliferation in SMCs of SV than IMA independent of tethered receptors, suggesting other thrombin receptors exist. These differences of thrombin receptor activation in IMA and SV may be important in the development of and therapy for graft disease.

Prognostic Significance of Multiple Previous Percutaneous Coronary Interventions in Patients Undergoing Elective Coronary Artery Bypass Surgery

Background— A possible relationship between increased perioperative risk during coronary artery bypass grafting (CABG) and previous percutaneous coronary intervention (PCI) is debatable. We sought to determine the impact of previous PCI on patient outcome after elective CABG. Methods and Results— Between January 2000 and January 2005, 2626 consecutive patients undergoing first-time isolated elective CABG as the primary revascularization procedure (group 1) were evaluated for in-hospital mortality and major adverse cardiac events (MACEs) and were compared with 360 patients after single PCI (group 2) and with 289 patients after multiple PCI sessions (group 3) before elective CABG. Unadjusted univariate and risk-adjusted multivariate logistic-regression analysis revealed previous multiple PCIs to be strongly associated with in-hospital mortality (odds ratio [OR], 2.24; 95% confidence interval [CI], 1.52 to 3.21; P<0.001) and MACEs (OR, 2.28; 95% CI, 1.38 to 3.59; P<0.001). To control for selection bias, a computed propensity-score matching based on 13 patient characteristics and preoperative risk factors was performed separately comparing group 1 versus 2 and group 1 versus 3. After propensity matching, conditional logistic-regression analysis confirmed previous multiple PCIs to be strongly associated with in-hospital mortality (OR, 3.01; 95% CI, 1.51 to 5.98; P<0.0017) and MACEs (OR, 2.31; 95% CI, 1.45 to 3.67; P<0.0004). Conclusions— In patients with a history of multiple PCI sessions, perioperative risk for in-hospital mortality and MACEs during subsequent elective CABG is increased.

Sternal closure techniques and postoperative sternal wound complications in elderly patients

OBJECTIVE Postoperative sternal wound complications (PSWC) including deep sternal wound infection (DSWI) and sternal dehiscence (SD) cause significant morbidity and mortality. Elderly patients with several risk factors are particularly prone to suffer PSWC. METHODS We present (I) a subset of 86 patients, all aged > or =75 years out of 339 cardiac surgery patients prospectively randomised to receive either conventional sternal closure or a Robicsek type closure. Primary end-points were SD and DSWI; secondary end-points included a composite of clinical parameters; (II) we retrospectively assessed data of 54/5273 patients with mediastinitis regarding the influence of advanced age. In addition, we report an epidemiological overview of different sternal closure techniques. RESULTS (I) The Robicsek technique showed an impact on SD and DSWI, and several secondary end-points: ventilator support (p=0.03), postoperative blood loss (p=0.04), and chest pain >3 days (p=0.04). (II) A total of 54/5273 (1.02%) patients developed postoperative mediastinitis. Twelve out of 54 (22%) patients died within 6 months of the initial operation. Predictors of mortality were insulin-dependent diabetes mellitus (p=0.05), renal insufficiency (p=0.01), delayed sternal closure (p=0.05), ICU-stay >10 days (p=0.01), and methicillin-resistant Staphylococcus aureus (p=0.03) or fungal infection (p=0.02). CONCLUSIONS No statistical difference in sternal dehiscence or mediastinitis was found irrespective of whether the bilateral and longitudinal parasternal closure or the conventional peri/trans-sternal wiring technique was used, but there was an obvious, positive influence on sternal dehiscence, deep sternal wound infection, and clinical parameters. However, the study population is relatively small.

Pulmonary hypertension and lung transplantation

ZusammenfassungDie pulmonale Hypertonie ist eine schwerwiegende und lebenslimitierende Erkrankung, die oftmals junge Menschen betrifft. Trotz wesentlicher Verbesserungen der medikamentösen Optionen bietet nur die Lungentransplantation einen kurativen Ansatz mit Wiederherstellung der Belastbarkeit. Allerdings sollte die Transplantation aufgrund des Organspendermangels und der Entwicklung der chronischen Abstoßung im Verlauf nur als letzte therapeutische Option angesehen werden. Die Vorstellung in einem erfahrenen Transplantationszentrum sollte eher früh als spät erfolgen, um eine rechtzeitige Listung zur Transplantation zu gewährleisten. Dabei sollte eine gründliche Evaluation stattfinden, gefolgt von Kontrollen in regelmäßigen Abständen, um frühzeitig eine Verschlechterung des Zustands zu erfassen. Die Doppellungentransplantation hat sich in den meisten Zentren gegenüber der Einzellungentransplantation aufgrund einer besseren 5-Jahres-Überlebensrate und einer erniedrigten Anzahl postoperativer Komplikationen bewährt. Die Herz- und Lungentransplantation sollte in Anbetracht der ähnlichen Überlebensraten und der Organknappheit nur in besonderen Fällen durchgeführt werden.AbstractBackground:With the development of effective drug treatment in the last 2 decades, lung transplantation has become the final option in the management of pulmonary arterial hypertension (PAH). Its main advantage is the curative aspect with recovery of cardiopulmonary capacity. Scarcity of donor organs and chronic graft rejection, however, remain serious limitations to short- and long-term success, and emphasize the need for judicial patient selection. Timely presentation of the patient to the transplant center is of critical importance.Indication:Guidelines have been presented by the International Society for Heart and Lung Transplantation (ISHLT), the American Thoracic Society (ATS) and the American Society of Transplant Physicians (ASTP) in the year 1998. Selection criteria are clinical status (NYHA [New York Heart Association] ≥ III and progressing, right heart insufficiency symptoms), hemodynamic data (mean pulmonary arterial pressure > 55 mmHg, systolic arterial pressure < 120 mmHg, cardiac index < 2 l/min/m2, central venous pressure > 15 mmHg, right heart function on echocardiography), and functional parameters (peak oxygen uptake < 10–12 ml/kg/min, 6-min walk test [MWT] < 332 m). Functional parameters have been shown to correlate with a 1-year mortality of 40% with a 6-MWT < 332 m, of 50% with a peak oxygen uptake < 10.4 ml/kg/min, and of 70% with a systolic arterial pressure < 120 mmHg. Combinations of the above lead to a 1-year survival of 23%. Mean survival of patients with primary pulmonary hypertension (PPH) is 2.8 years and is reduced to 6 months, when NYHA IV is reached (National Institutes of Health-PPH Registry 2002). These data underline the potential survival benefit from transplantation for patients with advanced lung failure due to PAH.Transplantation:Single lung, bilateral lung and heart-lung transplantation are the transplantation procedures available. Even though heart-lung transplantation was the first procedure to be performed in 1981, bilateral lung transplantation is the procedure most commonly performed at present. Choice of transplantation procedure should be made after thorough evaluation, taking the potential reversibility of right ventricular dysfunction after the operation into account (Figure 1). Hemodynamic instability from right and/or left ventricular failure, however, may complicate early postoperative management. Heart and lung transplantation should only be considered, if structural heart damage is present. Lung function improves immediately postoperatively and increases in the following 6 months. Most patients have normal function studies 1 year after transplantation.Statistics:The Registry of the ISHLT (01/1982–06/2003) reports PAH as primary diagnosis in 4.2% of all lung transplantations (457/10,959) and 24.3% (550/2,263) of all heart-lung transplantations. This corresponds to 1.1% of all single (66/5,793) and 7.6% of all bilateral lung transplantations (391/5,166). Single lung transplantation is associated with shorter ischemia, cardiopulmonary bypass and operation time. The procedure, however, is accompanied by ventilation/perfusion mismatch, a higher likelihood of reperfusion injury and less functional reserve in case of progressive chronic rejection. The advantages of bilateral lung transplantation are under discussion, particularly as 5-year survival seems to be higher in some centers. Heart and lung transplantation is reported to have similar results as bilateral lung transplantation (Table 1), showing survival advantages only in patients with Eisenmenger’s syndrome or ventricular septal defect. Bilateral lung transplantation, therefore, is the procedure of choice at the Essen Transplant Center, provided donor organs are available.Conclusion:Thoracic transplantation has become a feasible therapeutic option in terminal PAH patients. Judicious patient selection, choice and timing of procedure are critical to a successful outcome.

Surgical treatment for massive pulmonary embolism

ZusammenfassungDie fulminante Lungenembolie wird nur noch selten chirurgisch behandelt. Die Operation wird als „Ultima-Ratio“-Therapie insbesondere bei Patienten mit kardiopulmonaler Reanimation angesehen. Vor dem Hintergrund eines erheblichen Anteils von Patienten mit residualer Obstruktion nach Lysetherapie mit der Gefahr der Entwicklung einer chronischen pulmonalen Hypertonie und besserer Risikostratifizierung haben einzelne Zentren wieder mehr Patienten einer offenen chirurgischen Embolektomie zugeführt. Hier sind Überlebensraten bis 89% in der perioperativen Phase erzielt worden. Möglich war dies durch Operationen am schlagenden, normothermen Herzen unter Verwendung spezieller Instrumente, wie sie bei der Pulmonalisthrombendarteriektomie Verwendung finden. Die Bestätigung dieser guten Ergebnisse bei noch hämodynamisch stabilen Patienten mit mäßiger bis starker Einschränkung der rechtsventrikulären Funktion durch die Autoren und andere rechtfertigt den Einsatz dieses Verfahrens an Kliniken mit angeschlossener Herzchirurgie in einer früheren Phase, in welcher der Patient noch nicht reanimationspflichtig ist. Die Durchführung einer kontrollierten, randomisierten Studie zur Erfassung des tatsächlichen Stellenwerts im Vergleich zur Lysetherapie wäre wünschenswert im Sinne einer bestmöglichen Therapie für den Patienten.AbstractSurgical embolectomy for massive pulmonary embolism (PE) has become a rare procedure. Often, it is viewed as a last-chance option for patients undergoing cardiopulmonary resuscitation after massive PE. Thus thrombolytic therapy has become the treatment of choice. However, a significant proportion of patients suffers from residual obstruction after thrombolytic therapy and faces the development of chronic pulmonary hypertension. Therefore, some centers have regained interest in surgical embolectomy after improved risk stratification and reported very good results. Perioperative survival rates up to 89% have been reported. This was accomplished by surgery on the ECC-(extracorporeal circulation-)supported, beating, normothermic heart and utilization of special instruments. These encouraging results have been confirmed by the authors and others in patients with stable systemic hemodynamics but moderate to severe right ventricular dysfunction. The more widespread use of surgical embolectomy seems warranted. A randomized, controlled trial is overdue to determine the benefits of this therapy in stable patients compared with thrombolytic therapy if “best-practice” therapy is to be achieved for the patients’ benefit.

Sport nach Herztransplantation@@@Physical Exercise Following Heart Transplantation

Zusammenfassung.Durch die Verpflanzung eines gesunden Herzens kann einem schwerstkranken Patienten die Chance gegeben werden, wieder aktiv am Leben teilzunehmen. Dennoch können Herztransplantatempfänger trotz der guten Leistungsfähigkeit im Alltag und im Sport in Bezug auf die Adaptation bei Belastung und ihre maximale aerobe Kapazität nicht mit gesunden Leistungssportlern verglichen werden. In diesem Beitrag werden die möglichen Ursachen wie kardiale Denervierung, diastolische Dysfunktion, die Reduktion der Muskelmasse bei reduzierter Kapillarisierung oder eine endotheliale Dysfunktion diskutiert. Weitere limitierende Faktoren sind genetisch-metabolischer Genese im Rahmen der Grunderkrankung. Durch intensives aerobes Training kann die maximale Ausdauer nach Herztransplantation jedoch deutlich verbessert werden, und zusammen mit Krafttraining lassen sich die Nebeneffekte der immunsuppressiven Therapie reduzieren. Durch Ausdauertraining ist auch eine bessere Kontrolle der Risikofaktoren für die Transplantatvaskulopathie möglich. Aus diesem Grund sollte die Langzeittherapie der Transplantationspatienten von einem Ausdauertraining begleitet sein.Abstract.Heart transplantation has the potential to change a patient with a life-threatening illness into an active healthy person with a potentially excellent quality of life. Survival with excellent allograft function for 10 years is now common for the majority of patients. However, exercise performance remains impaired when compared to healthy subjects. Reasons include a decrease of maximal heart rate, cardiac output and oxygen uptake, which are present after heart transplantation. The role of these abnormalities may differ as a function of time after surgery. Possible reasons like cardiac denervation, diastolic dysfunction, and endothelial dysfunction are discussed in this article. Furthermore, exercise capacity may be diminished because of peripheral limitations associated with physical deconditioning, abnormal muscle structure and function or pharmacological side effects. Endurance and strength training may greatly improve muscle function and maximal aerobic performance as well as reduce side effects of immunosuppressive therapy. Exercise should be considered a valuable tool in the long-term treatment after heart transplantation.

Donor heart selection and outcomes: An analysis of over 2,000 cases

BACKGROUND Decision-making when offered a donor heart for transplantation is complex, and supportive data describing outcomes according to acceptance or non-acceptance choices are sparse. Our aim was to analyze donor heart acceptance decisions and associated outcomes at a single center, and after subsequent acceptance elsewhere. METHODS This investigation was a retrospective analysis of data obtained from the University of Vienna Medical Center and Eurotransplant centers for the period 2001 to 2015. RESULTS Our center accepted 31.8% (699 of 2,199) of donor hearts offered. Unlike other centers, the acceptance rate, with or without transplantation, did not increase over time. Of the donor hearts rejected by our center, 38.1% (572 of 1,500) were later accepted elsewhere. Acceptance rates were twice as high for donor hearts initially rejected for non-quality reasons (339 of 601, 56.4%) compared with initial rejection for quality reasons (233 of 899, 25.9%). Three-year patient survival rate was 79% at Vienna; for donor hearts initially rejected by Vienna for non-quality reasons or quality reasons, it was 73% and 63%, respectively (p < 0.001). Outcomes at other centers after transplantation of grafts rejected by Vienna varied according to the reason for rejection, with good 3-year survival rates for rejection due to positive virology (77%), high catecholamines (68%), long ischemic time (71%), or low ejection fraction (68%), but poor survival was observed for hearts rejected for hypernatremia (46%), cardiac arrest (21%), or valve pathology (50%). CONCLUSIONS A less restrictive policy for accepting donor hearts at our center, particularly regarding rejection for non-quality reasons or for positive virology, high catecholamine levels, longer ischemic time, or low ejection fraction, could expand our donor pool while maintaining good outcomes.

Cardiac Surgery is Safe in Female Patients with a History of Breast Cancer - Focus on Coronary Artery Bypass Grafting and Periprocedural Blood Loss

Objectives: In cardiac surgery candidates, a concomitant history of breast cancer suggests adverse outcomes. Particularly, the possibility of internal mammary artery utilization after (hemi-)thoracic irradiation is frequently discussed. Secondary, blood loss, wound healing and incidence of mediastinitis are important issues. However, publications focusing on these issues are limited. Methods: In a case-control study, we analyzed 46 patients with previously treated breast cancer undergoing cardiac surgery matched to 135 control subjects. Patients were analyzed regarding internal mammary artery (IMA) utilization, blood loss and substitution and frequent perioperative complications as well as long-term mortality. Results: No significant differences between groups were observed regarding duration of surgery, IMA utilization, postoperative infections and mortality. Also, IMA preparation side and number of harvested vessels was independent of the priorly irradiated thoracic field in the breast cancer group. A pronounced decline of hemoglobin/hematocrit was evident within the first 6 postoperative hours (3.3 ± 1.8 versus 2.6 ± 1.8 mg/dl; p = 0.02) in breast cancer patients not related to a signifcantly increased drainage loss but associated with an increase of INR (0.31 ± 0.19 versus 0.21 ± 0.21; p < 0.01). Conclusions: In breast cancer patients, cardiac surgical procedures can safely be performed with comparable short- and long-term results. Extracorporeal circulation strategies should be adapted to compensate for surgery-related blood loss.