Pushing the boundaries of innovation: the potential of ex vivo organ perfusion from an interdisciplinary point of view.

Ex vivo machine perfusion (EVMP) is an emerging technique for preserving explanted solid organs with primary application in allogeneic organ transplantation. EVMP has been established as an alternative to the standard of care static-cold preservation, allowing for prolonged preservation and real-time monitoring of organ quality while reducing/preventing ischemia-reperfusion injury. Moreover, it has paved the way to involve expanded criteria donors, e.g., after circulatory death, thus expanding the donor organ pool. Ongoing improvements in EVMP protocols, especially expanding the duration of preservation, paved the way for its broader application, in particular for reconditioning and modification of diseased organs and tumor and infection therapies and regenerative approaches. Moreover, implementing EVMP for in vivo-like preclinical studies improving disease modeling raises significant interest, while providing an ideal interface for bioengineering and genetic manipulation. These approaches can be applied not only in an allogeneic and xenogeneic transplant setting but also in an autologous setting, where patients can be on temporary organ support while the diseased organs are treated ex vivo, followed by reimplantation of the cured organ. This review provides a comprehensive overview of the differences and similarities in abdominal (kidney and liver) and thoracic (lung and heart) EVMP, focusing on the organ-specific components and preservation techniques, specifically on the composition of perfusion solutions and their supplements and perfusion temperatures and flow conditions. Novel treatment opportunities beyond organ transplantation and limitations of abdominal and thoracic EVMP are delineated to identify complementary interdisciplinary approaches for the application and development of this technique.

Surgical Restoration of Antero-Apical Left Ventricular Aneurysms: Cardiac Computed Tomography for Therapy Planning.

Background: Surgical ventricular restoration (SVR) leads to functional improvement by volume reduction and restoration of left ventricular (LV) geometry. Our purpose was to refine the planning for SVR using cardiac computed tomography (CCT). Methods: The possibility to anticipate the postoperative residual LV volume was assessed using CCT in 205 patients undergoing SVR combined with coronary artery bypass grafting (77%), mitral valve repair/replacement (19%) and LV thrombectomy (19%). The potential of CCT to guide the procedure was evaluated. Additionally, the predictive value of CCT characteristics on survival was addressed. Results: 30-day, 1- and 5-year survival was 92.6, 82.7, and 72.1%, respectively, with a marked reduction of NYHA class III-IV quota after surgery (95.1% vs. 20.5% in the follow-up). Both pre- and postoperative LV end-systolic volume index (LVESVI) were predictive of all defined endpoints according to the following tertiles: preoperative: <74 ml/m2, 74-114 ml/m2 and >114 ml/m2; postoperative: <58 ml/m2, 58-82 ml/m2 and >82 ml/m2. On average, a 50 ml/m2 increase of preoperative LVESVI was associated with a 35% higher hazard of death (p = 0.043). Aneurysms limited to seven antero-apical segments (1-7) were associated with a lower death risk (n = 60, HR 0.52, CI 0.28-0.96, p = 0.038). LVESVI predicted by CCT was found to correlate significantly with effectively achieved LVESVI (r = 0.87 and r = 0.88, respectively, p < 0.0001). Conclusions: CCT-guided SVR can be performed with good mid-term survival and significant improvement in HF severity. CCT-based assessment of achievable postoperative LV volume helps estimate the probability of therapeutic success in individual patients.

Predictive Value of Two-Dimensional Speckle-Tracking Echocardiography in Patients Undergoing Surgical Ventricular Restoration.

Objectives: Parameters of left ventricular (LV) mechanics, obtained from speckle-tracking echocardiography (STE), were found to be of prognostic value in patients with heart failure and those who underwent cardiac surgery. This study aimed to assess the value of STE in patients scheduled to undergo surgical ventricular restoration (SVR). Methods: A total of 158 consecutive patients with baseline STE who underwent SVR due to an LV anteroapical aneurysm were included in the analysis. Preoperative longitudinal STE parameters were evaluated for their association with an outcome, defined as all-cause mortality, LV assist device implantation, or heart transplantation. The echocardiographic follow-up to assess the change in the regional function of the segments remote from the aneurysm was performed in 43 patients at a median of 10 months [interquartile range (IQR): 6-12.7 months] after SVR. Results: During a median follow-up of 5.1 years (IQR: 1.6-8.7 years), events occurred in 68 patients (48%). Less impaired mean basal end-systolic longitudinal strain (BLS) with a cutoff value ≤ -10.1 % demonstrated a strong association with event-free survival, also in patients with an LV shape corresponding to an intermediate shape between aneurysmal and globally akinetic. Initially hypo- or akinetic basal segments with preoperative end-systolic strain ≤ -7.8% showed a greater improvement in wall motion at the short-term follow up. Conclusion: Patients with less impaired preoperative BLS exhibited a better event-free survival after SVR, also those with severe LV remodeling. The preserved preoperative segmental longitudinal strain was associated with a greater improvement in regional wall motion after SVR. BLS assessment may play a predictive role in patients with an LV anteroapical aneurysm who are scheduled to undergo SVR.

Cardiac Myxomas Show Elevated Native T1, T2 Relaxation Time and ECV on Parametric CMR.

Introduction: While cardiac tumors are rare, their identification and differentiation has wide clinical implications. Recent cardiac magnetic resonance (CMR) parametric mapping techniques allow for quantitative tissue characterization. Our aim was to examine the range of values encountered in cardiac myxomas in correlation to histological measurements. Methods and Results: Nine patients with histologically proven cardiac myxomas were included. CMR (1.5 Tesla, Philips) including parametric mapping was performed in all patients pre-operatively. All data are reported as mean ± standard deviation. Compared to myocardium, cardiac myxomas demonstrated higher native T1 relaxation times (1,554 ± 192 ms vs. 1,017 ± 58 ms, p < 0.001), ECV (46.9 ± 13.0% vs. 27.1 ± 2.6%, p = 0.001), and T2 relaxation times (209 ± 120 ms vs. 52 ± 3 ms, p = 0.008). Areas with LGE showed higher ECV than areas without (54.3 ± 17.8% vs. 32.7 ± 18.6%, p = 0.042), with differences in native T1 relaxation times (1,644 ± 217 ms vs. 1,482 ± 351 ms, p = 0.291) and T2 relaxation times (356 ± 236 ms vs. 129 ± 68 ms, p = 0.155) not reaching statistical significance. Conclusions: Parametric CMR showed elevated native T1 and T2 relaxation times and ECV values in cardiac myxomas compared to normal myocardium, reflecting an increased interstitial space and fluid content. This might help in the differentiation of cardiac myxomas from other tumor entities.

Minimally invasive left ventricular reconstruction of a postinfarction, anterior left ventricular scar (BioVentrix Revivent TC procedure).

Surgical ventricular reconstruction is a proven option for treating patients who have heart failure due to a postinfarction scar or an aneurysm of the left ventricle. The BioVentrix Revivent TC System offers a reliable alternative to the conventional, more invasive surgical ventricular restoration. The system requires no sternotomy, no heart-lung machine, and no cardioplegic arrest.  In this video tutorial, we present our technique for using the Revivent TC System to reconstruct the normal left ventricular shape and volume in a patient with a postinfarction, anteroapical scar.

Functional tricuspid valve insufficiency after cardiac transplantation: Which factor is the most important?

Objectives: Tricuspid insufficiency (TI) is the most common valvular complication following orthotopic heart transplantation (HTx) and in serious cases is associated with increased mortality. In this study, we analyze the possible variables influencing TI following HTx and aim to identify the most important risk factors and mechanisms responsible for functional TI development and progression. Methods: We identified the incidence of TI within our institute in 857 of 1515 patients who underwent HTx using the biatrial anastomosis technique in the years between 1986 and 2010. The risk factors that could influence TI were retrospectively analyzed in detail in a representative group of 152 patients with identical TI distribution as found in the entire program. Patients of the group were subdivided into 2 groups according to the severity of TI: patients with TI grade ≤2 and those with TI grade >2. Impact on long-term survival (>15 years) was assessed. Results: In univariable analysis, study variables such as age of recipient (P = .027), donor to recipient right atrium anterior wall ratio (P < .001), tricuspid annulus anterior to septal leaflet excursion ratio (P = .001), dialysis (P = .026), and total biopsy number (P = .003) showed significant differences. The variables, height of recipient (P = .080), body mass index donor to body mass index recipient ratio (P = .080), and number of biopsies with more than moderate grade (P = .067) showed a trend toward significance in the development of severe TI after HTx. In multivariable analysis, we found an independent significant association between TI after HTx and donor to recipient right atrium anterior wall ratio, number of biopsies, and dialysis. Conclusions: Changes in tricuspid annulus geometry, number of biopsies, and dialysis are the most important risk factors for the development and progression of TI following cardiac transplantation. It could be prevented using modified operative techniques, noninvasive diagnostic modalities, and intensified ultrafiltration. In patients with biatrial anastomosis technique with generous atrial cuff, the presence of TI greater than grade 2 did not impact long-term survival.

Temporary mechanical circulatory support for refractory heart failure: the German Heart Center Berlin experience.

BACKGROUND: Temporary mechanical circulatory support (MCS) offers a valuable option for treatment of refractory heart failure. We present our experience with selected MCS devices in cardiogenic shock of different etiologies. METHODS: We retrospectively studied patients who were treated in our institution between 01/2016 and 07/2018. Patients receiving only veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support were excluded. Left ventricular support patients received Impella; right ventricular support was conducted using Levitronix CentriMag. RESULTS: Thirty-seven patients received an Impella left ventricular assist device (LVAD). Etiology was: acute on chronic ischemic cardiomyopathy (ICMP; n=12), acute myocardial infarction (AMI; n=11), dilated cardiomyopathy (DCMP; n=7) and toxic cardiomyopathy (TCMP; n=2). Two patients presented with postcardiotomy shock and acute myocarditis, respectively. In one case, Takotsubo cardiomyopathy was diagnosed. Impella was used solely in 28 patients (Impella group) with an in-hospital survival of 37%. In nine patients, Impella was used in combination with extracorporeal life support (ECLS) implantation (ECMELLA group)-in-hospital survival was 33%. In the Impella group six patients recovered, six received a long-term VAD and 16 died on device. In the ECMELLA group one patient recovered, three received a long-term VAD and five died. The majority of CentriMag implantations as a right ventricular assist device (RVAD) were necessary after LVAD implantation (n=52); of these patients, 14 recovered, eight received long-term VAD and 30 died. The remaining 17 patients were supported by RVAD due to AMI (n=7); postcardiotomy (n=7); right heart failure after heart transplantation (n=2) and ICMP (n=1). Six of these patients recovered, two required long-term VAD and nine died. CONCLUSIONS: Survival after MCS implantation for left as well as right heart failure in cardiogenic shock remains low, but is superior to that of patients without mechanical support. Short-term MCS remains an option of choice if right, left or biventricular support is needed.

Effect of surgical incision management on wound infections in a poststernotomy patient population.

Skin breakdown and infiltration of skin flora are key causative elements in poststernotomy wound infections. We hypothesised that surgical incision management (SIM) using negative pressure wound therapy over closed surgical incisions for 6-7 days would reduce wound infections in a comprehensive poststernotomy patient population. 'All comers' undergoing median sternotomy at our institution were analysed prospectively from 1 September to 15 October 2013 (study group, n = 237) and retrospectively from January 2008 to December 2009 (historical control group, n = 3508). The study group had SIM (Prevena™ Therapy) placed immediately after skin suturing and applied at -125 mmHg for 6-7 days, whereas control group received conventional sterile wound tape dressings. Primary endpoint was wound infection within 30 days. Study group had a significantly lower infection rate than control group: 1·3% (3 patients) versus 3·4% (119 patients), respectively (P < 0·05; odds ratio 2·74). In the study group, when the foam dressing was removed after 6-7 days, the incision was primarily closed in 234 of 237 patients (98·7%). SIM over clean, closed incisions for the first 6-7 postoperative days significantly reduced the incidence of wound infection after median sternotomy. Based on these data SIM may be cost-effective in patients undergoing cardiac surgery.

Neurohumoral and inflammatory markers for prediction of right ventricular failure after implantation of a left ventricular assist device.

PURPOSE: Implantation of a left ventricular assist device (LVAD) is an established treatment for end-stage heart failure. Right ventricular dysfunction develops in 20%-50% of patients after device implantation, leading to prolonged hospital stays and elevated mortality rates. However, prediction of right ventricular failure remains difficult. METHODS: A total of 40 patients who received an LVAD for chronic end-stage heart failure between May 2001 and December 2002 were evaluated. The patients were divided retrospectively into two groups: group I (n = 26), with no apparent postoperative right ventricular failure; and group II (n = 14), with right ventricular failure after implantation defined by the presence of two of the following criteria during the first week after surgery: mean arterial pressure ≤ 55 mmHg, central venous pressure ≥ 16 mmHg, mixed venous saturation ≤ 55%, cardiac index <2 l/min/m(2), inotropic support score >20 units or an apparent need for mechanical right ventricular support. Hemodynamic, echocardiographic, neurohumoral, and inflammatory parameters were evaluated 24 h before implantation of the LVAD. RESULTS: Levels of procalcitonin, neopterin, n-terminalpro-brain natriuretic peptide, and big endothelin-1 were significantly lower in group I: 0.106 vs. 0.322 ng/ml, P = 0.048; 10.5 vs. 20.7 ng/ml, P = 0.018; 6322 vs. 17174 pg/ml, P = 0.032; 1.6 vs. 19.5 pg/ml, P = 0.02, respectively. Levels of creatinine kinase and creatinine were significantly lower in group I than in group II: 24 vs. 40 U/l, P = 0.034; 1.3 vs. 2.3 mg/dl, P = 0.008, respectively. CONCLUSION: Preoperative evaluation of markers of inflammation and neurohumoral activation may provide additional information for predicting right ventricular failure after implantation of an LVAD.

Tricuspid incompetence and geometry of the right ventricle as predictors of right ventricular function after implantation of a left ventricular assist device.

BACKGROUND: Implantation of a left ventricular assist device (LVAD) is an established treatment for end-stage heart failure. Right ventricular (RV) dysfunction develops in 20% to 50% of patients after LVAD implantation, leading to prolonged ICU stay and elevated mortality. However, the prediction of RV failure remains difficult. METHODS: The pre-operative echocardiographic parameters, tricuspid incompetence (TI), RV end-diastolic diameter (cut-off >35 mm), RV ejection fraction (cut-off <30%), right atrial dimension (cut-off >50 mm) and short/long axis ratio (cut-off >0.6), were analyzed retrospectively in 54 patients. Patients were divided into two groups. One group consisted of patients with RV failure (n = 9), as defined by the presence of two of the following criteria in the first 48 hours after surgery: mean arterial pressure < or =55 mm Hg; central venous pressure > or =16 mm Hg; mixed venous saturation < or =55%; cardiac index 20 units; or need for an RVAD. The other patients comprised the non-RV-failure group (n = 45). RESULTS: The RV failure group had a significantly higher short/long axis ratio of the RV (0.63 vs 0.52, p = 0.03; odds ratio 4.4, p = 0.011). For patients with a short/long axis ratio of the RV of <0.6, RV failure occurred in 7% of patients, as compared with 50% for patients with a ratio > or =0.6 (p = 0.013). Among patients with TI Grade III or IV, 75% developed RV failure as compared with 12% in patients with TI Grade I or II (p = 0.054). The odds ratio for RV failure after LVAD implantation for TI Grade III or IV was 4.7 (p = 0.012). CONCLUSIONS: Pre-operative evaluation of tricuspid incompetence and RV geometry may help to select patients who would benefit from biventricular support.

Natriuretic peptides and E-selectin as predictors of acute deterioration in patients with inotrope-dependent heart failure.

OBJECTIVE: In patients with inotrope-dependent end-stage heart failure the timely application of the most suitable treatment, i.e. heart transplantation, implantation of a ventricular assist device or conservative treatment, is a key issue for therapeutic success. METHODS: Seventy-six inotrope-dependent patients with end-stage heart failure were enrolled. Measurements of hemodynamics, routine laboratory parameters, and clinical examination were performed daily. Additionally, natriuretic peptides (BNP and NT-proBNP) and E-selectin were measured at the end of the study. The patients were retrospectively divided into groups with regard to the following end-points: Group I-deterioration into cardiogenic shock after an initially stable clinical course (n=26); Group II-stable clinical course without deterioration into cardiogenic (n=41); Group III-weaning from inotropic support (n=9). RESULTS: One day before cardiogenic shock occurred, BNP, NT-proBNP and E-selectin were significantly elevated in group I compared with group II. A logistic regression model showed that only BNP and E-selectin were independent predictors of clinical deterioration on the following day. The odds ratio (OR) for E-selectin using a cut-off point of 65ng/ml was 8.7 and for BNP using a cut-off of 500pg/ml it was 4.8. In combination, the OR increased to 11.1. Continuous decrease of NT-proBNP predicted patients in whom weaning from inotropes was possible. CONCLUSIONS: While routine parameters did not predict the clinical course, elevated BNP and E-selectin independently predicted cardiogenic shock on admission and 1 day before its occurrence. The combination showed increased predictive value.