Cenk Oezpeker

Everolimus exposure in cardiac transplant recipients is influenced by concomitant calcineurin inhibitor.

In two separate pharmacokinetic studies, the drug interaction between immunosuppressive agents was examined in a total of 12 cardiac transplant recipients by conversion of the concomitant immunosuppressant. In six patients under continuous tacrolimus therapy, the concomitant drug azathioprine was converted to everolimus (PK-TAC study). No significant effect on tacrolimus pharmacokinetic parameters was observed. In the second study in which the patients were converted from cyclosporine to tacrolimus under continuous everolimus therapy (PK-EVL study), a significant decrease in everolimus predose concentration (from 4.2 to 2.3 μg/L), maximum concentration (from 9.1 to 5.9 μg/L), and area under the concentration time curve (mean values decreased from 64.2 to 33.7 μg*h/L) was found, indicating a lower everolimus exposure. A pharmacokinetic interaction between cyclosporine and everolimus has been described previously for healthy volunteers after single-dose application and presumably originates from a comparatively greater inhibition of hepatic CYP3A4 or P-glycoprotein efflux transporter with a low-dose cyclosporine regimen. Our results confirm this interaction under clinical conditions and suggest close drug monitoring when converting the calcineurin inhibitor under concomitant mammalian target of rapamycin-inhibitor therapy.

Systemic Thrombolysis Versus Device Exchange for Pump Thrombosis Management: A Single-center Experience.

In patients with left ventricular assist device (LVAD) implants, pump thrombosis is a potential life-threatening complication. In a retrospective data analysis, we compared clinical outcomes in 50 patients with HeartWare (HW) or HeartMate II implants undergoing device exchange (DEx; n = 21) or systemic thrombolysis (STL; n = 29) for pump thrombosis. Primary end-point was survival up to 90 days postintervention. Secondary end-points were the need for blood products postintervention, duration of intensive care unit stay, in-hospital stay, 90 day and 2 year therapy failure (the need for additional surgical or nonsurgical intervention because of pump thrombosis), and 2 year survival. Ninety-day survival was 89.3% in the STL group and 91.0% in the DEx group (p = 0.901). Compared with the DEx group, the average use of different blood products was lower (p < 0.001), and duration of intensive care unit stay and in-hospital stay tended to be shorter in the STL group (p values = 0.086 and 0.048, respectively). However, 90 day freedom from therapy failure was significantly lower in the STL group than in the DEx exchange group (p = 0.027) and so was 2 year freedom from therapy failure (p = 0.006). Two-year survival was comparable between groups (p = 0.267). Our data indicate that STL can be considered as a therapeutic option in LVAD patients with pump thrombosis.

Permanent atrial fibrillation and 2-year clinical outcomes in patients with a left ventricular assist device implant.

Atrial fibrillation (AF) may increase the risk of thromboembolic (TE) complications in patients with left ventricular assist devices (LVADs). In a single-center study, we investigated 205 patients with sinus rhythm (SR group) and 117 patients with AF (AF group). Our main read outs were 2 year overall survival (primary end point), perioperative right heart failure (RHF), and 2 year freedom from stroke, pump thrombosis, and gastrointestinal bleeding (secondary end points). Oral anticoagulation was performed with phenprocoumon (international normalized ratio target range: 2.3–2.8) and aspirin (100 mg/day). Propensity score (PS) adjustment was used for statistical analysis. Two year survival was 65.4% (n = 134) in the SR group and 51.3% (n = 60) in the AF group. The PS-adjusted hazard ratio (HR) of 2 year mortality was higher in the AF group than in the SR group (HR = 1.48 [95% confidence interval (CI): 1.02–2.15; p = 0.038]). Right heart failure was a more frequent cause of death in the AF group than in the SR group (p = 0.008). The PS-adjusted odds ratio of perioperative RHF was for the AF group (reference: SR group) 1.32 (95% CI: 0.80–2.18; p = 0.280). The PS-adjusted 2 year HRs of TE and bleeding events were comparable between both groups and were for stroke, pump thrombosis, and gastrointestinal bleeding (reference: SR group) 0.90 (95% CI: 0.53–1.55; p = 0.714), 0.76 (95% CI: 0.14–4.31; p = 0.639), and 1.01 (95% CI: 0.60–1.70; p = 0.978), respectively. Our data indicate that AF increases midterm mortality, but does not influence the risk of stroke, pump thrombosis, and gastrointestinal bleeding. The higher midterm mortality in AF patients is most likely disease-related and should have no influence on LVAD implantation.

Tricuspid valve repair in patients with left-ventricular assist device implants and tricuspid valve regurgitation: propensity score-adjusted analysis of clinical outcome

OBJECTIVES In end-stage heart failure patients with left-ventricular assist device implantation and tricuspid valve (TV) regurgitation grade >2, the surgical strategy for TV regurgitation is unclear at present. We aimed to compare clinical outcomes in patients receiving left-ventricular assist device (LVAD) implants with or without TV repair (TVR). METHODS We included 58 patients with TV regurgitation grade >2 in our data analysis. Thirty-two patients received TVR during LVAD implantation (TVR+ group), whereas 26 patients did not receive TVR (TVR- group). We assessed demographic and various preoperative clinical and echocardiographic parameters in both groups. The primary end-point was survival up to 1 year. Secondary end-points were the incidence of prolonged mechanical ventilatory support, rethoracotomy, early and late right heart failure and liver or kidney failure. RESULTS Preoperatively, the two groups differed according to heart failure diagnosis, need for inotropic support and haemodynamic/echocardiographic parameters such as transpulmonary gradient, cardiac index and the ratio of the right-ventricular end-diastolic diameter to the left-ventricular end-diastolic diameter. The survival rate up to 1 year was 53.1% in the TVR+ group and 73.1% in the TVR- group (P = 0.176). The propensity score (PS)-adjusted 1-year mortality risk with the TVR- group as a reference was 3.05 for the TVR+ group (95% confidence interval: 0.84-11.11; P = 0.091). Secondary end-points did not differ significantly between study groups. CONCLUSIONS Data indicate that end-stage heart failure patients with TV regurgitation grade >2 undergoing LVAD implants do not benefit from concomitant TVR. Results have to be confirmed by prospective studies.

Systemic Thrombolysis Is an Alternative Therapeutic Option for Pump Thrombosis with Acceptable Risks.

We thank Dr. Spiliopoulos and colleagues for their interest in our management of pump thrombosis. We agree that device exchange is the gold standard of treating pump thrombosis and that systemic thrombolysis (STL) can only be a treatment option in selected patients. One important criterion for STL is timing. Thrombolysis should be performed as soon as possible after the onset of clinical symptoms of pump thrombosis, within 24 hours at the latest. This implies that patients are instructed in recognizing signs of device thrombosis manifestation (low pump flow, increased power consumption, hematuria). Moreover, outpatients should maintain intensive contact with their clinic, and readmission to the hospital should be possible very rapidly after the onset of signs of device thrombosis. Because pump thrombosis needs an intervention as soon as possible, therapy can already be started during transportation to the specialized center. In our decision of treating device thrombosis, we take into account that thrombotic material, because of its fibrous nature, is only partly susceptible to thrombolytic agents. Besides timing of STL, pump design may also play a role. With respect to HeartMate II, any thrombus that forms within the components of the device may become very solid and firm. Although in the STL group of our study freedom from therapy failure did not differ significantly between patients with HeartMate II implants and HeartWare implants,1 we are very cautious in performing STL in patients with HeartMate II implants. Moreover, device exchange is easier to perform in HeartMate II patients than in HeartWare patients, because of better access to the pump head. Therefore, in our opinion, STL can be a first-line therapy in HeartWare patients, whereas in HeartMate II patients, device exchange should be the first line of therapy. We are also well aware of the high risk of thrombus recurrence after STL. This risk is illustrated by our finding that compared with device exchange STL is associated with markedly lower freedom from therapy failure.1 However, if necessary, device exchange can already be safely performed 12 hours after STL. It is also noteworthy that in the STL group of our study the relatively high risk of therapy failure was not associated with an increased mortality risk. Taken together, in our opinion, STL represents an alternative therapeutic option for pump thrombosis with acceptable risks.

Minimally Invasive Redo-Aortic Valve Replacement: Reduced Operative Times as Compared to Full Sternotomy

OBJECTIVES  Increasing experience with minimally invasive cardiac (MIC) aortic valve (AV) replacement makes AV reoperations (rAVR) an appealing alternative to conventional redo surgery. The aim of the study was to compare the perioperative outcome after isolated MIC versus full-sternotomy (FS) rAVR. METHODS  We retrospectively analyzed data of 116 patients from three centers who underwent rAVR by using a FS (n = 70, 60.3%) or a partial upper sternotomy approach (n = 46, 39.7%). Both groups were compared in terms of 30-day mortality by using binary-logistic regression models. Further the EuroSCORE II was used to adjust for preoperative conditions in a multivariable model. Perioperative times and complications were compared between the two groups. RESULTS  There was no statistically significant difference in perioperative mortality between FS (n = 5, 7.1%) and MIC (n = 1, 2.2%) rAVR in the original population (odds ratio [OR] 3.462, 95% confidence interval [CI] 0.391-30,635, p = 0.264) and after adjusting for EuroSCORE II (OR 2.759, 95% CI 0.298-25.567, p = 0.372). Cardiopulmonary bypass- (115.5 minutes vs. 137.5 minutes, p = 0.070) and cross-clamp times (69.0 minutes vs. 81.0 minutes, p = 0.028) were reduced in the MIC group. There was a lower prevalence of postoperative renal failure requiring renal replacement therapy (RRT) in the MIC group 0 and 8.6% (p = 0.041), respectively. No differences were detected between the groups regarding postoperative complications. CONCLUSION  MIC rAVR is associated with reduced cardiopulmonary and cross-clamp times as well as the need for RRT as compared with FS. MIC-rAVR seems to be a viable option in surgical candidates for AV reoperations.

Mitral Valve Surgery via Partial Upper Sternotomy: Closing the Gap between Conventional Sternotomy and Right Lateral Minithoracotomy

BACKGROUND  Minithoracotomy (MT) has gained broad acceptance for mitral valve surgery (MVS) in the last decade. In the presence of defined limitations of MT, however, full sternotomy (FS) is still widely preferred. We assume that the less investigated partial upper sternotomy (PS) will permit the gap between MT and FS in MVS to be closed. The purpose of this study is to investigate a valid less invasive alternative to MT for isolated MVS or multivalve surgery. METHODS  This retrospective analysis includes data on 1,639 patients, who underwent either isolated or combined primary MVS at our department from May 2011 to August 2017. Out of these, 663 patients were operated via MT access. One-hundred three patients had been judged as not suitable for MT but feasible for PS approach in which 53.4% (n = 55) had isolated MVS and 46.6% patients (n = 48) underwent multivalve surgery. Concomitant myocardial revascularization was performed in 2.9% of the study patients (n = 3). RESULTS  Operative, 90-day, and 1-year mortality in the PS-cohort was 0, 1.0% (n = 1), and 3.3% (n = 3), respectively. During a median follow-up time of 1,115 days (interquartile range 398-1806), all-cause mortality was 5.8% (n = 6). Operative times for cardiopulmonary-bypass and cross-clamping were 167 minutes (140-198) and 107 minutes (93-132), respectively. Median length of stay at the intensive care unit and hospital was 1 (1-2) and 7 days (7-10), respectively. CONCLUSION  The presented results demonstrate that there is a cohort of patients, who are not candidates for MT in MVS but may be operated successfully by an alternative less invasive approach.

Changes in Von Willebrand factor profile predicts clinical outcomes in patients on mechanical circulatory support

The associations between mechanical circulatory support (MCS), acquired von Willebrand syndrome (AvWS), and clinical outcome are incompletely understood.

A Comparison between HeartMate II and HeartWare LVAD, a Single Center Experience

Purpose LVAD implantation is an established therapy for end-stage cardiac failure. The most implanted devices are HeartMate II (HMII) and HeartWare (HW). The goal of this study is to compare both devices in terms of morbidity and mortality. Methods and Materials Since 2007 100 HMII and 97 HW LVADs are implanted in our center. The mean age in the HW group was lower (51.0 vs 57.4, p=0.001), more patient were ventilated preoperatively (30.9% vs 13%, p=0.002), ECMO support was more frequent in the HW group (16.5% vs 6%, p=0.019). Both groups did not show differences in Intermacs levels, hemodynamic parameter, gender, blood parameters, intention to treat and cause of cardiac failure. Results Operation duration, blood loss and the need for blood transfusion were comparable in both groups. The mean duration of ICU stay postoperatively did not show a difference. Early and late right heart failure (p=0.804, p=0.602) as the need for RVAD implantation were comparable (p=0.296). Driveline infection occurred in 24.7% of the patients in the HW group vs 19% in the HMII group (p=0.66). 8.2% of the patients in the HW group vs 8.4% in the HMII group suffered an embolic CVA (p=0.965), hemorrhagic CVA were comparable (10.3% HW group, 9.5%HMII group, p=0.846). Thrombolysis, because of pump thrombosis, was performed in 3.1% in the HW group, 4.0% in the HMII group (n.s.), replacement was necessary in 3.1% of the HW patients vs 9.0% of the HMII patients (n.s.). One year mortality was 69.8% in the HW group vs 67.3% in The HMII group (n.s.). Conclusions Despite more riskfactors for morbidity and mortality in the HW group (Ventilation, ECMO preoperatively), the results were comparable for the HW and the HMII group. Both devices are feasible, HW seems to have advantages in ECMO patiens and patients on ventilation.