Is implantable cardioverter defibrillator surgery in patients with an implanted left ventricular assist device safe under uninterrupted oral anticoagulation?

BACKGROUND: Implantable cardioverter-defibrillator (ICD) surgery in patients with implanted left ventricular assist devices (LVAD) is associated with an increased risk of bleeding complications because of the need to ensure that these patients are adequately anticoagulated. Our study aimed to evaluate the safety of our new strategy of uninterrupted oral anticoagulation compared to heparin-bridging during the surgical interval. METHODS: Between January 2009 and January 2020, 116 patients with LVAD underwent ICD surgery. Since January 2015, 60 patients were operated under continued sufficient oral anticoagulation with a vitamin k antagonist (VKA group). Fifty-six patients underwent a heparin-bridging regimen (heparin group). Demographics, perioperative data, complications, and mortality were analyzed. RESULTS: Bleeding complications attributable to the surgical intervention occurred more often (19.6% vs. 10.0%, p = 0.142) and at a higher rate of re-exploratory surgery (14.3% vs. 5.0%, p = 0.088) in the heparin group without reaching statistical significance. Moreover, the heparin group patients' postoperative total length of stay was 10 days longer (17.8 ± 23.8 days vs. 8.3 ± 9.5 days, p = 0.007). There were no procedure-related deaths, no thromboembolic events, and no LVAD-related thrombosis. CONCLUSION: Our strategy of uninterrupted oral anticoagulation is safe and results in a reduction by more than half the number of days in hospital without an increase in adverse events.

Evaluation of Strategies in the Management of Infective Aortic Valve Endocarditis at German Cardiac Surgical Departments.

BACKGROUND: Surgical treatment of infective aortic valve endocarditis (AVE) remains a therapeutic challenge, necessitating interdisciplinary approach to limit morbidity and mortality in this high-risk cohort. With a considerable spectrum of available laboratory testings, imaging techniques, as well as operative strategies developed in recent years, there is a lack of standardization across cardiac surgical departments in Germany. Thus, the optimal treatment strategy of AVE has yet to be defined. METHODS: A nationwide survey on infective AVE was conducted, including 64 cardiac surgical departments responding to a 41-item questionnaire. The evaluation included common surgical practice, routine diagnostic steps, surgical techniques, perioperative medical treatment, as well as postoperative management. RESULTS: Remarkable differences were observed among the participating institutions, including the following components of the treatment: (1) standardization and extent of the use of imaging techniques and (2) success rate in identification AVE-causing germs, (3) timing of operation in case of cerebral embolization, and (4) choice of valve prosthesis for aortic valve replacement for infective AVE. CONCLUSION: The findings of this survey underline the need for a nationwide registry to further elucidate the nature and course of AVE in Germany, as well as to serve as a solid basis for prospective trials, addressing the most important clinical purposes in the diagnosis and treatment of AVE.

Evaluation of risk factors for a fulminant Clostridium difficile infection after cardiac surgery: a single-center, retrospective cohort study.

BACKGROUND: Clostridium difficile (CD) is the most common pathogen causing nosocomial diarrhea. The clinical presentation ranges from mild diarrhea to severe complications, including pseudomembranous colitis, toxic megacolon, sepsis, and multi-organ failure. When the disease takes a fulminant course, death ensues rapidly in severe and complex cases. Preventive screening or current prophylactic therapies are not useful. Therefore, this study was conducted to detect risk factors for a fulminant CD infection (CDI) in patients undergoing cardiac surgery. METHODS: Between April 1999 and April 2011, a total of 41,466 patients underwent cardiac surgery at our institution. A review of our hospital database revealed 1256 patients (3.0%) with post-operative diarrheal disease who tested positive for CD; these patients comprised the cohort of this observational study. A fulminant CDI occurred in 153 of these patients (12.2%), which was diagnosed on the basis of gastrointestinal complications, e.g. pseudomembranous colitis, and/or the need for post-cardiac surgery laparotomy. Demographic, peri-operative, and survival data were analyzed, and predictors of a fulminant CDI were assessed by binary logistic regression analysis. RESULTS: The 30-day mortality was 6.1% (n = 77) for the entire cohort, with significantly higher mortality among patients with a fulminant CDI (21.6% vs. 4.0%, p <  0.001). Overall mortality (27.7%, n = 348) was also higher for patients with a fulminant course of the disease (63.4% vs. 22.8%, p <  0.001), and a laparotomy was required in 36.6% (n = 56) of the fulminant cases. Independent predictors of a fulminant CDI were: diabetes mellitus type 2 (OR 1.74, CI 1.15-2.63, p = 0.008), pre-operative ventilation (OR 3.52, CI 1.32-9.35, p = 0.012), utilization of more than 8 units of red blood cell concentrates (OR 1.95, CI 1.01-3.76, p = 0.046) or of more than 5 fresh-frozen plasma units (OR 3.38, CI 2.06-5.54, p <  0.001), and a cross-clamp time > 130 min (OR 1.93, CI 1.12-3.33, p = 0.017). CONCLUSIONS: We identified several independent risk factors for the development of a fulminant CDI after cardiac surgery. Close monitoring of high-risk patients is important in order to establish an early onset of therapy and thus to prevent a CDI from developing a fulminant course after cardiac surgery.

Impact of sleep disordered breathing on short-term post-operative outcome after elective coronary artery bypass graft surgery: a prospective observational study.

Sleep disordered breathing (SDB) is common in patients with coronary disease, but its impact on post-operative recovery after coronary artery bypass graft surgery (CABG) is unclear. We therefore determined the effects of SDB on post-operative outcome after elective CABG.In this prospective two-centre study, 219 patients due to receive elective CABG underwent cardiorespiratory polygraphy for SDB prior to surgery and were monitored for post-operative complications. The primary end-point was a composite of 30-day mortality or major post-operative complications (cardiac, respiratory, surgical, infectious, acute renal failure or stroke). Key secondary end-points were single components of the primary end-point.SDB was present in 69% and moderate/severe SDB in 43% of the CABG patients. There was no difference in the composite of 30-day mortality or major postoperative complications between patients with and without SDB (OR 0.97, 95% CI 0.49-1.96) and between patients with moderate/severe SDB and no/mild SDB (OR 1.07, 95% CI 0.55-2.06). However, moderate/severe SDB was associated with higher rates of mortality (crude OR 10.1, 95% CI 1.22-83.5), sepsis (OR 2.96, 95% CI 1.17-7.50) and respiratory complications (OR 2.85, 95% CI 1.46-5.55).Although SDB was not associated with higher overall morbidity/mortality, moderate/severe SDB may increase the risk of death, and septic and respiratory complications, after elective CABG.

Pharmacokinetics of intraluminally administered serum papaverine for spasm prophylaxis of the internal mammary artery.

BACKGROUND: Papaverine (Paveron N™ Linden Arzneimittel Vertrieb GmbH, Germany) is a widely used agent for preventing spasm in mammary artery preparations. The question addressed in this study is whether the intraluminal administration of papaverine can result in detectable absorption of the drug into the systemic arterial circulation. METHODS: In 15 patients (age 65 ± 6 years; body mass index 28.9 ± 3.7), an internal mammary artery (IMA) was prepared during coronary artery bypass grafting (CABG). A maximum of 3 mL of a 1 mg/1 mL diluted papaverine solution was injected intravascularly (intraluminally) for spasm prophylaxis. The IMA was closed proximally and distally with bulldog clamps. Blood samples were taken immediately after administration (T1), after 20 minutes (T2), and at the end of the operation (T3). Samples were measured in a liquid chromatography-tandem mass spectrometry (LC-MS/MS) system consisting of a binary pump from Agilent (Waldbronn, Germany) coupled to a high-throughput screening (HTS) PAL injection system (CTC, Zwingen, Switzerland) and a tandem mass spectrometer (API 4000, AB Sciex, Darmstadt, Germany). Papaverine was analyzed in positive mode using an electrospray ion source. Quantitation was performed using Analyst 1.5 software (AB Sciex, Darmstadt, Germany). RESULTS: The newly developed LC-MS/MS method was successfully established for the detection of papaverine in plasma samples. The highest plasma papaverine levels were determined at time point T1 (mean 54.7 ± 39 ng/mL, range 16.6-179 ng/mL). The concentration was already halved 20 minutes after administration (T2) (mean 23.3 ± 2 ng/mL, range 4.6-118 ng/mL). Because of the short half-life and the hemodilution in the extracorporeal circulation, at the end of the operation papaverine (T3) had already fallen to just above the limit of detection (mean 4.1 ± 3.9 ng/mL, range 1.3-16.9 ng/mL). At time point T1, a significant negative correlation was determined between plasma levels and systemic diastolic, but not systolic, blood pressure. CONCLUSION: Papaverine was successfully determined systemically in plasma by LC-MS/MS after intraluminal administration in the IMA. Systemic circulatory effects are dependent on the detected quantity. Group size and the absence of a control group are considerable limitations.

Invasive Giant B-Cell Lymphoma Mimicking Fulminant Pulmonary Embolism.

Background Cardiac non-Hodgkin's lymphoma is rare and has a poor prognosis. Here we report a rare case mimicking pulmonary embolism. Case Description A 38-year-old woman suffered from severe dyspnea after cesarean section. With the clinical picture of fulminant central pulmonary embolism, lysis therapy was initiated. Further deterioration necessitated extracorporeal membrane oxygenation (ECMO) support and cardiosurgical intervention. Intraoperatively, a massive intravascular tumor obstructed the pulmonary bifurcation and was found to be B-cell lymphoma. Aggressive excision and pulmonary tree reconstruction improved the critical condition and initiated convalescence. Conclusion High suspicion in central pulmonary embolism and early cardiosurgical therapy after ineffective lysis are essential.

ST-Segment Elevation Myocardial Infarction and Right Atrial Myxoma.

Background Cardiac myxoma is the most common primary cardiac tumor. Although benign, it can cause life-threatening complications due to embolization. Case Presentation We describe an ST-elevation myocardial infarction (STEMI) involving a giant right atrial myxoma and persisting foramen ovale (PFO) in a 64-year-old male patient and report on emergency percutaneous interventional therapy and subsequent cardiac surgery to remove the right atrial myxoma. Conclusion A right atrial myxoma, combined with a PFO, can cause a STEMI. Therefore, every acute coronary syndrome patient should undergo ultrafast exploratory emergency echocardiography to protect the physician from unpleasant surprises.

Visceral arterial compromise during intra-aortic balloon counterpulsation therapy.

BACKGROUND: Intraaortic balloon pump (IABP) therapy is a widely used method of circulatory support. Based on frequent findings of balloon malposition with visceral arterial compromise on computerized tomographic (CT) imaging studies, we conducted a systematic review of cardiac surgical IABP patients with available CT scans to determine reasons, incidence, and clinical relevance of malposition. METHODS AND RESULTS: From January 2007 to March 2009, a total of 621 of 7756 cardiac surgical patients (8.0%) received perioperative IABP support, of whom 63 (10.1%) received a thoracoabdominal CT scan during IABP support. Proximal and distal balloon positions were analyzed. The anatomic distance from the left subclavian artery to celiac trunk and aortic transverse diameter were measured in all patients and compared with implanted balloon dimensions. Mean age was 67.1±11.9 years; 33.3% were female, and height was 169±9 cm. Based on radiography, proximal balloon position was correct in 96.8% but only appropriate in 38.1% based on CT. In 61 of 63 patients, compromise of at least 1 visceral artery was found: celiac trunk, 96.8%; superior mesenteric artery, 87.3%; and renal arteries, 66.7%. Left subclavian artery to celiac trunk distance was 241±23 mm, and balloon length was 248±17 mm and corresponded to an anatomic to balloon length mismatch in 68.2%. Spinal deformations were found in 42.9%. Laparotomy for mesenteric ischemia was required in 23.8%. Hospital mortality rate was 60.3%. CONCLUSIONS: IABP malposition was commonly identified by CT. Reasons included incorrect proximal balloon position as well as an anatomic-to-balloon length mismatch. Thus, shorter than recommended balloon sizes and better positioning strategies had to be considered.

Does reasonable incomplete surgical revascularization affect early or long-term survival in patients with multivessel coronary artery disease receiving left internal mammary artery bypass to left anterior descending artery?

BACKGROUND: The objective was to evaluate the impact of complete revascularization (CR) versus reasonable incomplete surgical revascularization (IR) in others than left anterior descending artery territory on early and late survival in patients with multivessel coronary artery disease (CAD). METHODS AND RESULTS: During a 7-year period, 8.806 consecutive patients with multivessel CAD affecting the proximal left anterior descending artery or left main stem underwent sternotomy for isolated coronary artery bypass grafting including left internal mammary artery-left anterior descending artery bypass. A total of 936 patients (10.6%) had IR of the circumflex or right coronary artery territory. IR was based on the traditional classification. Follow-up was 3.5+/-2.2 years. Patient groups were comparable regarding age (CR 67.1 versus IR 67.6 years), ejection fraction (57.2% versus 57.5%), and logEuroscore (4.5% versus 4.5%). Patients receiving IR presented with more complex CAD. Mean number of distal anastomoses was 3.0+/-0.8 CR versus 2.4+/-0.6 IR. Operation time (176 versus 187 minutes) and cross-clamp time (52 versus 56 minutes) were longer in the IR group (P<0.001). Hospital mortality was 3.3% CR versus 3.2% IR (P=0.520). Independent risk factors for hospital mortality were age, pulmonary hypertension, chronic obstructive pulmonary disease, peripheral vascular disease, and emergency indication, but not IR (P=0.922). Arterial revascularization was protective. Cumulative survival at 1-year was 93.1% CR versus 93.6% IR and at 5 years 82.2 CR versus 80.9% IR (P=0.457). CONCLUSIONS: In presence of left internal mammary artery-to-left anterior descending artery bypass, reasonable IR of the circumflex or right coronary artery territory did not adversely affect early or long-term survival in patients with multivessel CAD. In patients presenting with 1 poor target vessel; however, IR is a good therapeutic option and the benefit of CR should be balanced against the risks.

[Coronary artery bypass surgery for the treatment of acute coronary syndromes]. / Stellenwert der koronaren Bypass operation in der Therapie der akuten Koronarsyndrome.

According to the current guidelines coronary revascularization in acute coronary syndromes (ACS) is primarily performed by percutaneous coronary interventions (PCI). However, in several scenarios like complex coronary pathologies, unsuccessful PCI, complicated PCI or cardiogenic shock, surgical coronary revascularization might be indicated. Then, timing of the operation is based on clinical symptoms, coronary artery pathology, and the type of underlying ACS (Figure 1). Surgical strategies among others include the use of beating-heart strategies. Furthermore, a modern perioperative management allows improved results in a more aged and comorbid patient population as well as in patients presenting with hemodynamic instability. In cardiogenic shock, a variety of different cardiopulmonary assist devices are available today including intra-aortic balloon pump, several ventricular assist devices, and extracorporeal membrane oxygenation (Figure 2).In the literature, results of coronary artery bypass grafting (CABG) in ACS patients vary significantly because of different patient populations, different timing of the operation, and different hemodynamic status. Thus, comparison of surgical concepts is almost impossible. Until today, randomized surgical trials for ACS patients are pending. However, hospital survival of > 95% is reported even in emergency CABG patients during the last 5 years (Table 1). For all surgical candidates a close and direct communication between interventionalist and cardiac surgeon is mandatory to early identify the best treatment strategy and to achieve best possible revascularization results.

Giant Intramural Right Ventricular Hematoma after PCI in a Patient with Condition after CABG.

Coronary artery perforation secondary to percutaneous coronary intervention (PCI) is a rare, but a potentially life-threatening complication. There is a misconception that cardiac tamponade rarely occurs in patients with prior coronary artery bypass grafting (CABG). We first describe a giant right ventricular intramural hematoma following PCI via a saphenous vein graft to treat a distal stenosis of the right coronary artery, and its successful treatment with redo cardiac surgery. Complex elective PCIs on patients after CABG should be performed in specialized centers with a well-established heart team that has the expertise to treat any of the potential complications.

Frequency and pattern of de-novo three-vessel and left main coronary artery disease; insights from single center enrolment in the SYNTAX study.

OBJECTIVES: To characterize the current patient population regarding extent and pattern of coronary artery disease (CAD) in a routine cardiac catheterization practice with special focus on de-novo three-vessel coronary artery and/or left main disease (3-VD/LM) during enrolment in the SYNTAX study (synergy between PCI with Taxus drug-eluting stent and cardiac surgery) comparing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) and coronary artery bypass grafting (CABG) in 3-VD/LM. METHODS: During a 4-month study enrolment period, a total of 3319 consecutive adult patients undergoing coronary angiography were prospectively recorded. Patients with de-novo 3-VD/LM were screened in the daily heart team conference by interventional cardiologists and cardiac surgeons concerning suitability for study enrolment. Complexity of CAD was quantified by the SYNTAX score. RESULTS: A total of 694 patients (20.9%) presented with 3-VD/LM, of which 271 had previous CABG and 232 previous PCI treatment. Of the 191 patients with de-novo 3-VD/LM, SYNTAX study exclusion criteria were present in 87 patients consisting mostly of acute myocardial infarction (n=47) or concomitant indications for additional heart surgery (n=35). A total of 104 patients (54.4% of all screened) were potentially suitable for study enrolment. Of these, 13 patients refused study participation, 10 presented with uncertain protocol adherence and 6 were already participating in other cardiovascular trials. A total of 67 patients were therefore enrolled in the SYNTAX study, representing 9.7% of 3-VD/LM and 35.1% of all screened patients. Twenty-four patients were not amenable for PCI and were therefore assigned to the CABG registry. Compared to the randomized cohort, these patients had more complex CAD (SYNTAX score 34 vs 26, p=0.003) with significantly more chronic coronary vessel occlusion (70.8% vs 22.5%, p=0.04). In the randomized cohort, CABG and PCI patients were comparable in age (PCI 69.7 years vs CABG 67.2 years), additive EuroSCORE (4.8 vs 4.4), EF (57.8% vs 52.4%), number of coronary lesions (4.5 vs 4.6), left main disease (42.9% vs 52.6%) and coronary vessel occlusion. CONCLUSIONS: Patients with de-novo 3-VD/LM represented a small proportion of patients undergoing coronary angiography at our center. However, SYNTAX study inclusion and randomization rates of these screened patients were high. Chronic vessel occlusion and high SYNTAX scores were more common in CABG registry patients compared to randomized patients.

Emergency coronary artery bypass graft surgery for acute coronary syndrome: beating heart versus conventional cardioplegic cardiac arrest strategies.

BACKGROUND: Aim of this study was to compare the outcome of beating heart versus conventional coronary artery bypass graft (CABG) strategies in acute coronary syndromes for emergency indications. METHODS AND RESULTS: 638 consecutive patients with acute coronary syndrome (ACS) receiving emergency CABG surgery via midline sternotomy from January 2000 to September 2005 were evaluated. Propensity score analysis was used to predict the probability of undergoing beating heart (BH) (n=240) versus cardioplegic cardiac arrest (CA) (n=398) strategies. Patients presented with stable hemodynamics (n=531) or in cardiogenic shock (CS) (n=107). Hospital and follow-up outcome was compared by propensity score adjusted multiregression analysis. BH included 116 on-pump and 124 off-pump (OPCAB) procedures. There was a propensity to operate CS patients on the beating heart (multivariate odds ratio [OR], 3.8; P=0.001). Under stable hemodynamics significant predictors for BH selection were logEuroSCORE >20% (OR, 2.05), creatinine >1.8 mg/dL (OR, 4.12), complicated percutaneous coronary intervention (OR, 1.88), ejection fraction <30% (OR, 2.64), whereas left main disease (OR, 0.68), circumflex artery (OR, 0.32), and 3-vessel disease (OR, 0.67) indicated preference for cardioplegic arrest. Time from skin incision to culprit lesion revascularization was significantly reduced in BH patients. BH surgery led to a significant benefit in terms of less drainage loss, less transfusion requirement, less inotropic support, shorter ventilation time, lower stroke rate, and shorter intensive care unit stay. In CS, BH was associated with lower incidence of stroke, inotropic support, acute renal failure, new atrial fibrillation and sternal wound healing complications. In CS patients, hospital mortality rate was reduced when using beating heart strategies (P=0.048). Overall survival, major adverse cerebral and cardiovascular event rate, and repeated revascularization was comparable during a 5-year follow-up. CONCLUSIONS: Beating heart strategies are associated with an improved hospital outcome and comparable long-term results for high-risk patients presenting acute coronary syndrome with or without CS.

Pacemaker dependent patients with device infection--a modified approach.

A modified surgical concept for temporary cardiac pacing in pacemaker dependent patients requiring total removal of infected devices is presented. Proximal to the infected pocket a permanent bipolar pacing lead is placed transcutaneously into the ipsilateral subclavian or jugular vein. The lead is placed in the right ventricle and fixed into the skin using the suture sleeve. Pacing is established by connecting an external pacing generator. Subsequently the infected device can be removed completely. After wound dressing the externalized lead is connected to a permanent VVI-pacemaker allowing for prolonged temporary pacing.

On-pump beating heart versus off-pump coronary artery bypass surgery-evidence of pump-induced myocardial injury.

OBJECTIVE: By maintaining native coronary blood flow in on-pump beating heart surgery (OnP-BH) and comparing with OPCAB strategy pump-related effects on myocardial injury and cardiac dysfunction could be specifically differentiated from ischemia/reperfusion-related consequences of surgical coronary revascularization. METHODS: In a randomized-prospective design, 40 elective patients with normal EF and three vessels coronary artery disease (left main disease excluded) were assigned to OPCAB or OnP-BH surgery. Before coronary occlusion and 1, 30, 60, and 90 min after reperfusion with the LIMA graft, coronary sinus (CS) blood was sampled to determine intraoperative myocardial ischemia (pH, lactate, pO2) and oxidative stress (malondialdehyde, MDA). Additionally to CS blood arterial blood was analyzed 4, 12, and 24 h postoperatively to determine myocardial necrosis (CK-MB, cardiac troponin I), myocardial dysfunction (NT-proBNP) and inflammation (C-reactive protein). RESULTS: Groups were identical with regards to age and gender (OPCAB 63.0+/-6.0 versus OnP-BH 65.3+/-3.9 y, 20% female patients). Number of grafts were 3.0+/-0.5 in OPCAB versus 2.9+/-0.3 in OnP-BH (n.s.) with 44 versus 34% bilateral IMAs and 56 versus 50% complete arterial revascularization. Regarding ischemia, intraoperatively only lactate values increased significantly in the OnP-BH group. Significantly higher CK-MB and troponin I levels were found from LIMA-LAD flow release onwards to 4 h postoperatively in the OnP-BH group. NT-proBNP levels were significantly higher in the OnP-BH group during the entire study period. CRP levels were higher in the OnP-BH group 12 and 24 h postoperatively. CONCLUSIONS: In this randomized study on routine coronary patients with normal ventricular function, OPCAB revealed less myocardial injury than OnP-BH. These findings implicate that CPB slightly affects the myocardium.

Morphological, electrophysiological and coupling characteristics of bone marrow-derived mononuclear cells-an in vitro-model.

OBJECTIVE: Transplantation of bone marrow-derived mononuclear cells (BMC) may be suitable to prevent myocardial remodeling and improve left ventricular function after myocardial infarction. However, it is unknown whether or not cardiomyocytes and BMCs can form functioning cell-to-cell coupling and develop adequate electrophysiological properties. METHODS: BMCs were isolated from minipig leg bones, treated with 5-azacytidine (10 microM) for 24 h, cultured for 7 days and labeled with a fluoroscopic dye (DIL). BMCs were cocultured with spontaneously beating cardiomyocytes of neonatal rats. On days 4, 7 and 14 cocultured cells were analyzed. Immunhistochemistry (Connexin 43, alpha-actinin) was used to assess cardiomyogenic differentiation. Action potential characteristics were recorded in whole cell patch clamp mode and to investigate intercellular communication a second gap junction permeable fluoroscopic dye was brought into BMCs by microinjection (Lucifer yellow, LY). RESULTS: From day 7 in coculture BMCs beated synchronously with neonatal rat cardiomyocytes. On day 14, 55.9% of BMCs expressed alpha-actinin and 98.3% were positive for gap junction protein connexin 43. BMC action potential duration (APD90) was mean 11.1 ms with dV/dt(max) of 26.8 V/s and similar to atrial cardiac type. However, microinjection of LY revealed only little dye transfer into adjacent rat cardiomyocytes. CONCLUSIONS: Cocultured BMCs have the potential for early expression of muscle specific proteins in about 60% after 14 days and for cardiac gap junction proteins. Synchronous beating indicates an effective electromechanical coupling. In this heterologous setting we could prove only weak metabolic coupling.

Fusion of bone marrow-derived stem cells with cardiomyocytes in a heterologous in vitro model.

OBJECTIVE: Recent studies have demonstrated that transplanted bone marrow-derived stem cells (BMCs) possess a broad differentiation potential and are able to form new cardiomyocytes. However, the identity of BMCs as true cardiomyocytes is still ambiguous. Therefore, we investigated the fate of transplanted fluorescence labeled BMCs and cardiomyocytes in co-culture. METHODS: For cell tracking we used two different fluorescent probes, Vybrant/DiO and Vybrant/DiI. BMCs were taken from human sternal marrow, purified using a Ficoll-gradient-centrifugation, treated with 5-azacytidine and stained with Vybrant/DiO. Furthermore, isolated spontaneous beating cardiomyocytes of neonatal rats (CM) were labeled with Vybrant/DiI. Thereafter, the BMCs were transplanted into CM-cultures and investigated on day 1, 4, 7, 14 and 28 using two-color fluorescence phenotyping by laser-scanning-cytometry (LSC). Two-color positive cells were harvested by patch-clamp technique and beta-MHC mRNA expression was analyzed by single-cell PCR. RESULTS: Two different morphological phenotypes were observed by LSC. First, isolated DiO labeled BMCs without contact or with direct cell contact to DiI labeled CMs. Second, some BMCs and CMs were double positive for DiO/DiI spontaneously forming hybrids. This population increased by 18% from day 1 to 4 and decreased only slightly until day 28. Additionally, few two-color positive cell formations expressed both human and rat specific beta-MHC mRNA as well as only human beta-MHC mRNA indicating that cell-fusion and transdifferentiation has occurred. CONCLUSION: These observations provide in vitro evidence for spontaneous cell fusion and transdifferentiation of BMCs in co-culture, raising the possibility that the observed phenomenons may contribute to development or maintenance of these cell types.

Is the new EuroSCORE II a better predictor for transapical aortic valve implantation?

OBJECTIVES: Conventional surgical risk scores are used to identify suitable candidates for transapical aortic valve implantation (TA-AVI) at present. However, these scores do not consider multiple high-risk conditions, including porcelain aorta, mediastinal irradiation or frailty. The aim of this study was to compare the predictive ability of the new EuroSCORE II with the surgical risk scores currently in use. METHODS: From February 2006 to May 2011, 360 consecutive high-risk patients, age 81.6 ± 6.4 years, 64.4% female, were included using the Edwards SAPIEN™ prosthesis. The prognostic value of the EuroSCORE II was evaluated and compared with the logistic EuroSCORE and STS mortality score by receiver operating characteristics (ROC) curve analysis. In addition, a Spearman correlation analysis was performed, and a stepwise multivariate Cox regression used to identify the independent risk factors of mortality. RESULTS: The STS score and EuroSCORE II (r = 0.504, P < 0.001) showed a good correlation, while a strong correlation was found between the logistic EuroSCORE and EuroSCORE II (r = 0.717, P < 0.001). Thirty-day and in-hospital mortality rates were 10.6% (38 of 360) and 11.4% (41 of 360), respectively. In-hospital mortality rate was estimated by the logistic EuroSCORE: 30.0 ± 15.7%, the STS score: 11.7 ± 7.8% and the EuroSCORE II: 6.7 ± 5.1%. The prognostic values of the STS score, logistic EuroSCORE and the recent EuroSCORE II systems were analysed by ROC curve analysis for the prediction of 30-day (area under the curve, AUC: 0.64 vs 0.55 vs 0.50) and in-hospital mortality (AUC: 0.65 vs 0.54 vs 0.49). Multivariate regression analysis revealed length of preoperative hospital stay >5 days, body weight <65 kg, preoperative aortic annular diameter ≤ 20 mm, vital capacity <70% and concomitant mitral regurgitation >1+ as independent risk factors. CONCLUSION: In patients undergoing TA-AVI, the new EuroSCORE II correlates strongly with the logistic EuroSCORE, but is a poorer predictor of 30-day and in-hospital mortality than the STS score. A true transcatheter aortic valve implantation risk score would be desirable beyond the established scores.

The reverse remodeling effect of mesenchymal stem cells is independent from the site of epimyocardial cell transplantation.

OBJECTIVE: The transplantation of mesenchymal stem cells (MSCs) represents a promising approach for treating the ischemic and the nonischemic diseased heart. The positive effects of transplanting these cells could be shown, but the exact mechanisms remain unknown. We evaluated whether the injection site affects the improvement in left ventricular (LV) ejection fraction (EF) and angiogenesis in doxorubicin (Dox)-induced failing hearts. METHODS: Heart failure was induced in New Zealand white rabbits by doxorubicin treatment, followed by right ventricular MSC transplantation (RV-MSC, n = 6), LV MSC transplantation (LV-MSC, n = 6), sham treatment (sham group, n = 6), or no therapy (Dox group, n = 5). Healthy rabbits were used as control group (n = 8). Cells were isolated after bone marrow aspiration and transplanted locally into the ventricular myocardium. After 4 weeks, cardiac function and capillary density (CD31 staining) were measured. RESULTS: The transplantation of MSCs increased the EF significantly (LV-MSC, 39.0% ± 1.4%, and RV-MSC, 39.2% ± 2.6%, vs sham group, 29.8% ± 3.7%; P < 0.001), without significance between the MSC groups (P = 0.858). Neither the evidence of a transdifferentiation nor any signs of cell engraftment of transplanted cells could be found. The capillary density (capillaries/high-power field) increased in both MSC groups compared with the sham group (LV-MSC by 8.3% ± 3.4%; and RV-MSC, 8.1% ± 2.2%; P < 0.05), without significance between the two MSC groups (P = 0.927). CONCLUSIONS: Injection of autologous MSCs in doxorubicin-induced cardiomyopathic rabbit hearts improves EF and enhances angiogenesis. Despite local application, we observed global effects on heart function and capillary density without significant difference between right and LV injection. The paracrine mechanism might be one possible explanation for these findings.