Upper Hemi-Sternotomy Provides Benefit for Patients with Isolated or Combined Mitral Valve Surgery.

Background and objectives: Certain clinical and anatomical conditions are absolute or relative contraindications for safe mitral valve surgery via the right mini-thoracotomy access. It is uncertain whether patients with these contraindications may benefit from the less invasive approach via upper hemi-sternotomy compared to standard full sternotomy. Materials and methods: Out of 2052 mitral valve surgery patients, operated from 6/04 through 2/19, 1535 were excluded due to the different criteria for eligibility to both approaches. Out of these, 350 received full sternotomy and 167 upper hemi-sternotomy. After propensity score matching, 164 pairs were analyzed for operative variables, postoperative complications and 30-day and one-year survival. Results: Upper hemi-sternotomy was associated with a survival benefit of 30 days (99.4% vs. 82.1%; p < 0.001) and one-year (93.9% vs. 79.9% p < 0.001, HR 0.26, 95% CI 0.14-0.49). Cardiopulmonary bypass and aortic cross-clamp times were comparable in both groups. Upper hemi-sternotomy resulted in less low cardiac output syndrome (18.9% vs. 31.1%; p = 0.011); ventilation time (8 vs. 13 h; p < 0.001), length of intensive care stay (1 vs. 2 days; p < 0.001) and total hospital stay (8 vs. 9 days; p < 0.001) were shorter in the upper hemi-sternotomy group. Conclusion: In patients undergoing mitral valve surgery, upper hemi-sternotomy is associated with short- and mid-term survival benefits as well as lower postoperative complication rates compared to full sternotomy. Hence, the less invasive upper hemi-sternotomy can be a valid approach in patients with contraindications for right mini-thoracotomy.

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.

BACKGROUND: The associations between mechanical circulatory support (MCS), acquired von Willebrand syndrome (AvWS), and clinical outcome are incompletely understood. METHODS: In 128 heart failure patients with pulsatile MCS implants (65 total artificial heart or biventricular assist device implants, 63 left ventricular assist device [LVAD] implants) and 76 patients with continuous flow LVAD implants, we analyzed the von Willebrand factor (vWF) profile before (≤24 h) and 17.5 (standard deviation: 5.1) days after device implant. We determined vWF concentrations, vWF activity, and vWF collagen binding capacity and calculated ratios of vWF activity/binding capacity with vWF concentration. The relation of the vWF profile with clinical outcomes such as stroke, gastrointestinal bleeding, and survival was also evaluated. Events were assessed up to 1 year of device implant. RESULTS: All entities of vWF were already significantly elevated preoperatively and remained high after MCS implantation. The ratios of vWF activity/concentration (vWF:RCo/Ag) and collagen binding capacity/concentration (vWF:CBA/Ag) were significantly reduced preoperatively and remained low postoperatively, indicating AvWS. The preoperative alterations in the vWF profile were already present in patients without intra-aortic balloon pump and/or extracorporeal circulatory membrane oxygenation implants. The vWF profile was unrelated to postoperative stroke. However, a higher postoperative ratio of vWF:CBA/Ag was independently associated with increased gastrointestinal bleeding. In addition, a postoperative increase in vWF concentrations and activity were independent predictors of increased 1-year mortality. CONCLUSIONS: Our data indicate that AvWS is present in heart failure patients before device implantation, and is independently associated with clinical outcomes, especially with 1-year mortality.

One-Year Clinical Outcome in End-Stage Heart Failure: Comparison of "High Urgent" Listing for Heart Transplantation with Mechanical Circulatory Support Implantation.

BACKGROUND: Heart transplantation (HTx) is still considered the therapeutic gold standard in end-stage heart failure. METHODS: In "high urgent" (HU)-listed patients for HTx (n = 274) and patients receiving left ventricular assist device (LVAD) implants (n = 332), we compared 1-year overall survival (primary endpoint) and 1-year probability of HTx and therapy failure (the need for LVAD implantation in HU-listed patients or the need for HU listing in LVAD patients) (secondary endpoints). RESULTS: In the HU and LVAD group, 1-year survival was 86.8 and 64.7%, respectively (p < 0.001). The propensity score (PS)-adjusted hazard ratio of mortality did not differ between the groups and for the LVAD group (reference = HU group) was = 1.36 (95% confidence interval [CI]: 0.85-2.19; p = 0.198). The PS-adjusted hazard ratio for the failure to receive HTx for the LVAD group (reference = HU group) was = 9.77 (95% CI: 6.00-15.89; p < 0.001). The corresponding hazard ratio for therapy failure for the LVAD group was = 0.16, 95% CI: 0.10-0.27; p < 0.001). CONCLUSION: Despite considerable differences in the probability of HTx and therapy failure, 1-year overall survival was similar in HU and LVAD patients.

A qualitative improvement program for minimally invasive mitral surgery: technical advancements ameliorate outcome and operative times.

OBJECTIVES: Minimally invasive mitral valve surgery (MIMVS) has evolved over the last 2 decades. The aim of the study was to identify the impact of era and technical improvements on perioperative outcome after MIMVS. METHODS: A tota of 1000 patients (mean age: 60.8 ± 12.7 years, 60.3% male) underwent video-assisted or totally endoscopic MIMVS between 2001 and 2020 in a single institution. Three technical modalities were introduced during the observed period: (i) 3D visualization, (ii) use of premeasured artificial chordae (PTFE loops) and (iii) preoperative CT scans. Comparisons were made before and after the introduction of technical improvements. RESULTS: A total of 741 patients underwent isolated mitral valve (MV) procedure, whereas 259 received concomitant procedures. These consisted of tricuspid valve repair (208), left atrium ablation (145) and persistent foramen ovale or atrial septum defect (ASD) closure (172). The aetiology was degenerative in 738 (73.8%) patients and functional in 101 patients (10.1%). A total of 900 patients received MV repair (90%), and 100 patients (10%) underwent MV replacement. Perioperative survival was 99.1%, and periprocedural success 93.5% with a periprocedural safety of 96.3%. Improvement in periprocedural safety attributed to the lower rates of postoperative low output (P = 0.025) and less reoperations for bleeding (P < 0.001). 3D visualization improved cross-clamp (P = 0.001) but not cardiopulmonary bypass times. The use of loops and preoperative CT scan both had no impact on periprocedural success or safety but improved cardiopulmonary bypass and cross-clamp times (both P < 0.001). CONCLUSIONS: Increased surgical experience improves safety in MIMVS. Technical improvements are related to increased operative success and decreased operative times in patients undergoing MIMVS.

Predictors of safety and success in minimally invasive surgery for degenerative mitral disease.

OBJECTIVES: The aim of this study was to identify predictors of periprocedural success and safety in minimally invasive mitral valve surgery and to determine the impact of pathology localization and repair technique on reoperation-free survival. METHODS: We isolated 686 patients (mean age 60.5, standard deviation 12.3 years, 69.4% male) who underwent surgery for mitral valve prolapse between 2002 and 2020 in a single institution. Patients with concomitant disease, redo or mitral pathology other than degenerative mitral disease were excluded from the analysis. Periprocedural safety was defined as: freedom from perioperative death, myocardial infarction, stroke, use of extracorporeal membrane oxygenation or reoperation for bleeding. Operative success was defined as: successful primary mitral repair without conversion to replacement or to larger thoracic incisions, without residual mitral regurgitation > mild at discharge or reoperation within 30 days. Predictors for perioperative success and safety were identified using univariable and multivariable analyses. The impact of prolapse localization and repair technique on reoperation-free survival was assessed by Cox regression. RESULTS: The mitral repair rate and the need for concomitant tricuspid repair were 94.6% and 16.5%, respectively. Perioperative mortality occurred in 5 patients (0.7%). The criteria for perioperative safety and success were met in 646/686 (94.2%) and 648/686 (94.5%) patients, respectively. The absence of tricuspid disease requiring repair was the only independent predictor of safety in this cohort [hazard ratio (HR) 0.460 (0.225-0.941), P = 0.033]. The only independent predictor of operative success was the use of chordal replacement [0.27 (0.09-0.83), P = 0.022]. Reoperation-free survival was 98.5%, 94.5% and 86.9% at 1, 5 and 10 years, respectively. Posterior leaflet pathology demonstrated a higher reoperation-free survival as compared to other localizations (log-rank P = 0.002). The localization of leaflet pathology but not the repair method was an independent predictor for reoperation-free survival (HR 1.455, 95% confidence interval 1.098-1.930; P = 0.009). CONCLUSIONS: In minimally invasive mitral surgery for degenerative disease, chordal replacement yields higher rates of periprocedural success than leaflet resection. Posterior leaflet pathology is an independent predictor of reoperation-free survival.

Mechanical circulatory support does not reduce advanced myocardial fibrosis in patients with end-stage heart failure.

AIMS: Mechanical unloading by ventricular assist devices (VADs) has become increasingly important for the therapy of end-stage heart failure during the last decade. However, VAD support was claimed to be associated with partial reverse remodelling. Unfortunately, the literature describes the contradictory effects of VAD systems on cardiac fibrosis, a hallmark of cardiac remodelling. To clarify these inconsistent results, the effects on cardiac fibrosis before and after mechanical unloading in 125 patients were examined. METHODS AND RESULTS: Left ventricular myocardial tissue from ischaemic or non-ischaemic cardiomyopathy patients undergoing VAD implantation and subsequent cardiac transplantation and non-failing hearts of the control group were analysed for 4-hydroxyproline (4OH-P) content as a marker for collagen protein. In addition, collagen cross-linking and mRNAs of collagens I and III and transforming growth factor beta-1 were measured. 4OH-P content was significantly increased in failing hearts compared with the control group and increased (P < 0.05) after mechanical unloading (nmol/mg tissue, mean ± standard deviation: 16.74 ± 9.68 vs. 7.75 ± 2.39 and 18.57 ± 9.19). However, plotting of the 4OH-P ratios (post/pre-VAD) against the collagen content pre-VAD could be fitted by non-linear regression. Collagen cross-linking correlated strongly with the total collagen content in pre- and post-VAD myocardium (r2  = 0.73 and 0.71, respectively). In contrast to the total collagen content, all three mRNAs of fibrotic genes were significantly down-regulated during VAD support when compared to pre-VAD. CONCLUSIONS: This investigation of a comparably large patient cohort revealed that cardiac fibrosis was strongly increased in heart failure and increased even after mechanical unloading. The mRNAs of collagens I and III are independently regulated from the collagen protein.

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.

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.

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.

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 microg/L), maximum concentration (from 9.1 to 5.9 microg/L), and area under the concentration time curve (mean values decreased from 64.2 to 33.7 microg*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.