Heterogeneity in Clinical Practices for Post-Cardiotomy Extracorporeal Life Support: a Pilot Survey from the PELS-1 Multicenter Study.

BACKGROUND: High-quality evidence for post-cardiotomy extracorporeal life support (PC-ECLS) management is lacking. This study investigated the real-world PC-ECLS clinical practices. METHODS: This cross-sectional, multi-institutional, international pilot survey explored center organization, anticoagulation management, left ventricular unloading, distal limb perfusion, PC-ECLS monitoring and transfusions practices. Twenty-nine questions were distributed among 34 hospitals participating in the Post-cardiotomy Extra-Corporeal Life Support Study. RESULTS: Of the 32 centers [16 low-volume (50%); 16 high-volume (50%)] that responded, 16 (50%) had dedicated ECLS specialists. Twenty-six centers (81.3%) reported using additional mechanical circulatory supports. Anticoagulation practices were highly heterogeneous: 24 hospitals (75%) reported using patient's bleeding status as a guide, without a specific threshold in 54.2% of cases. Transfusion targets ranged 7-10 g/dL. Most centers used cardiac venting on a case-by-case basis (78.1%) and regular distal limb perfusion (84.4%). Nineteen (54.9%) centers reported dedicated monitoring protocols including daily echocardiography (87.5%), Swan-Ganz catheterization (40.6%), cerebral near-infrared spectroscopy (53.1%) and multimodal assessment of limb ischemia. Inspection of the circuit (71.9%), oxygenator pressure drop (68.8%), plasma free hemoglobin (75%), d-dimer (59.4%), lactate dehydrogenase (56.3%) and fibrinogen (46.9%) are used to diagnose hemolysis and thrombosis. CONCLUSIONS: This study shows remarkable heterogeneity in clinical practices for PC-ECLS management. More standardized protocols and better implementation of available evidence are recommended.

Preoperative Levosimendan therapy reduces postoperative right ventricular failure in patients undergoing left ventricular assist device implantation.

OBJECTIVES: Perioperative mortality and complications still remain high after left ventricular assist device (LVAD) implantation, especially in highly compromised patient cohorts. Here, we evaluate the effects of preoperative Levosimendan therapy on peri- and postoperative outcomes after LVAD implantation. METHODS: We retrospectively analysed 224 consecutive patients with LVAD implantation for end-stage heart failure between November 2010 and December 2019 in our centre with regard to short- and longer-term mortality as well as incidence of postoperative right ventricular failure (RV-F). Out of these, 117 (52.2%) received preoperative i.v. Levosimendan therapy within 7 days before LVAD implantation (Levo group). RESULTS: In-hospital, 30-day and 5-year mortality was comparable (in-hospital mortality: 18.8% vs 23.4%, P = 0.40; 30-day mortality: 12.0% vs 14.0%, P = 0.65; Levo vs control group). However, in the multivariate analysis, preoperative Levosimendan therapy significantly reduced postoperative RV-F but increased postoperative vasoactive inotropic score ([RV-F: odds ratio 2.153, confidence interval 1.146-4.047, P = 0.017; vasoactive inotropic score 24 h post-surgery: odds ratio 1.023, confidence interval 1.008-1.038, P = 0.002). These results were further confirmed by 1:1 propensity score matching of 74 patients in each group. Especially in the subgroup of patients with normal preoperative RV function, the prevalence of postoperative RV-F was significantly lower in the Levo- group as compared to the control group (17.6% vs 31.1%, P = 0.03; respectively). CONCLUSIONS: Preoperative Levosimendan therapy reduces the risk of postoperative RV-F, especially in patients with normal preoperative RV function without effects on mortality up to 5 years after LVAD implantation.

Impact of COVID-19 on incidence and outcomes of post-infarction mechanical complications in Europe.

OBJECTIVES: Post-acute myocardial infarction mechanical complications (post-AMI MCs) represent rare but life-threatening conditions, including free-wall rupture, ventricular septal rupture and papillary muscle rupture. During the coronavirus disease-19 (COVID-19) pandemic, an overwhelming pressure on healthcare systems led to delayed and potentially suboptimal treatments for time-dependent conditions. As AMI-related hospitalizations decreased, limited information is available whether higher rates of post-AMI MCs and related deaths occurred in this setting. This study was aimed to assess how COVID-19 in Europe has impacted the incidence, treatment and outcome of MCs. METHODS: The CAUTION-COVID19 study is a multicentre retrospective study collecting 175 patients with post-AMI MCs in 18 centres from 6 European countries, aimed to compare the incidence of such events, related patients' characteristics, and outcomes, between the first year of pandemic and the 2 previous years. RESULTS: A non-significant increase in MCs was observed [odds ratio (OR) = 1.15, 95% confidence interval (CI) 0.85-1.57; P = 0.364], with stronger growth in ventricular septal rupture diagnoses (OR = 1.43, 95% CI 0.95-2.18; P = 0.090). No significant differences in treatment types and mortality were found between the 2 periods. In-hospital mortality was 50.9% and was higher for conservatively managed cases (90.9%) and lower for surgical patients (44.0%). Patients admitted during COVID-19 more frequently had late-presenting infarction (OR = 2.47, 95% CI 1.24-4.92; P = 0.010), more stable conditions (OR = 2.61, 95% CI 1.27-5.35; P = 0.009) and higher EuroSCORE II (OR = 1.04, 95% CI 1.01-1.06; P = 0.006). CONCLUSIONS: A non-significant increase in MCs incidence occurred during the first year of COVID-19, characterized by a significantly higher rate of late-presenting infarction, stable conditions and EuroSCORE-II if compared to pre-pandemic data, without affecting treatment and mortality.

Degenerative changes of the aortic valve during left ventricular assist device support.

AIMS: Donor heart shortage leads to increasing use of left ventricular assist device (LVAD) as bridge-to-transplant or destination therapy. Prolonged LVAD support is associated with aortic valve insufficiency, representing a relevant clinical problem in LVAD patients. Nevertheless, the impact of LVAD support on inflammation, remodelling, and chondro-osteogenic differentiation of the aortic valve is still not clearly understood. The aim of the study is to evaluate the impact of LVAD support on structural and molecular alterations of the aortic valve. METHODS AND RESULTS: During heart transplantation, aortic valves of 63 heart failure patients without (n = 22) and with LVAD support (n = 41) were collected and used for analysis. Data on clinical course as well as echocardiographic data were analysed. Calcification and markers of remodelling, chondro-osteogenic differentiation, and inflammation were evaluated by computed tomography, by mRNA analysis and by histology and immunohistochemistry. Expression of inflammation markers of the LVAD group was analysed with regard to levels of C-reactive protein and driveline infections. Calcium accumulation and mRNA expression of determined markers were correlated with duration of LVAD support. Data were also analysed relating to aortic valve opening and aortic valve insufficiency. There was no difference in the frequency of cardiovascular risk factors or comorbidities between the patient groups. Expression of matrix metalloproteinase-9 (P = 0.007), alpha-smooth muscle actin (P = 0.045), and osteopontin (P = 0.003) were up-regulated in aortic valves of LVAD patients. Histological appearance of the aortic valve was similar in patients with or without LVAD, and computed tomography-based analysis not yet revealed significant difference in tissue calcification. Expression of interferon gamma (P = 0.004), interleukin-1 beta (P < 0.0001), and tumour necrosis factor alpha (P = 0.04) was up-regulated in aortic valves of LVAD patients without concomitant inflammatory cell infiltration and independent from unspecific inflammation. Expression of matrix metalloproteinase-2 (P = 0.038) and transforming growth factor beta (P = 0.0504) correlated negatively with duration of LVAD support. Presence of aortic valve insufficiency led to a significantly higher expression of interferon gamma (P = 0.007) in LVAD patients. There was no alteration in the determined markers in relation to aortic valve opening in LVAD patients. CONCLUSIONS: Left ventricular assist device support leads to signs of early aortic valve degeneration independent of support duration. Thus, the aortic valve of patients with LVAD support should be closely monitored, particularly in patients receiving destination therapy as well as in the prospect of using aortic valves of LVAD patients as homografts in case of bridge-to-transplant therapy.

Postcardiotomy Veno-Arterial Extracorporeal Membrane Oxygenation: Does the Cannulation Technique Influence the Outcome?

Objectives: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) may be cannulated using either central (cannulation of aorta) or peripheral (cannulation of femoral or axillary artery) access. The ideal cannulation approach for postcardiotomy cardiogenic shock (PCS) is still unknown. The aim of this study is to compare the outcome of patients with PCS who were supported with central vs. peripheral cannulation. Methods: This is a single-center retrospective data analysis including all VA-ECMO implantations for PCS from January 2011 to December 2017. The central and peripheral approaches were compared in terms of patient characteristics, intensive care unit (ICU) stay, hospitalization length, adverse event rates, and overall survival. Results: Eighty-six patients met the inclusion criteria. Twenty-eight patients (33%) were cannulated using the central approach, and 58 patients (67%) were cannulated using the peripheral approach. Forty-three patients (50%) received VA-ECMO in the operating room and 43 patients (50%) received VA-ECMO in the ICU. Central VA-ECMO group had higher EuroSCORE II (p = 0.007), longer cross-clamp time (p = 0.054), higher rate of open chest after the procedure (p < 0.001), and higher mortality rate (p = 0.02). After propensity score matching, 20 patients in each group were reanalyzed. In the matched groups, no statistically significant differences were observed in the baseline characteristics between the two groups except for a higher rate of open chests in the central ECMO group (p = 0.02). However, no significant differences were observed in the outcome and complications between the groups. Conclusions: This study showed that in postcardiotomy patients requiring VA-ECMO support, similar complication rates and outcome were observed regardless of the cannulation strategy.

Altered mRNA Expression of Interleukin-1 Receptors in Myocardial Tissue of Patients with Left Ventricular Assist Device Support.

Serum levels of cytokines interleukin 1 beta ( IL-1ß) and interleukin 33 (IL-33) are highly abnormal in heart failure and remain elevated after mechanical circulatory support (MCS). However, local cytokine signaling induction remains elusive. Left (LV) and right ventricular (RV) myocardial tissue specimens of end-stage heart failure (HF) patients without (n = 24) and with MCS (n = 39; 594 ± 57 days) were analyzed for cytokine mRNA expression level of IL-1B, interleukin 1 receptor 1/2 (IL-1R1/2), interleukin 1 receptor-like 1 (IL-1RL1), IL-33 and interleukin-1 receptor accessory protein (IL-1RaP). MCS patients showed significantly elevated IL-1B expression levels (LV: 2.0 fold, p = 0.0058; RV: 3.3 fold, p < 0.0001). Moreover, IL-1R1, IL-1RaP and IL-33 expression levels strongly correlated with each other. IL-1RL1 and IL-1R2 expression levels were significantly higher in RV myocardial tissue (RV/LV ratio IL-1R2 HF: 4.400 ± 1.359; MCS: 4.657 ± 0.655; IL-1RL1 HF: 3.697 ± 0.876; MCS: 4.529 ± 0.5839). In addition, IL1-RaP and IL-33 RV expression levels were significantly elevated in MCS. Furthermore, IL-33 expression correlates with C-reactive protein (CRP) plasma levels in HF, but not in MCS patients. Increased expression of IL-1B and altered correlation patterns of IL-1 receptors indicate enhanced IL-1ß signaling in MCS patients. Correlation of IL-1 receptor expression with IL-33 may hint towards a link between both pathways. Moreover, diverging expression in LV and RV suggests specific regulation of local cytokine signaling.

Less invasive surgical implant strategy and right heart failure after LVAD implantation.

BACKGROUND: Conventional median sternotomy (CMS) is still the standard technique utilized to implant left ventricular assist devices (LVADs). Recent studies suggest that less invasive surgery (LIS) may be beneficial; however, robust data on differences in right heart failure (RHF) are lacking. This study aimed to determine the impact of LIS compared with that of CMS on RHF outcomes after LVAD implantation. METHODS: An international multicenter retrospective cohort study was conducted across 5 centers. Patients were grouped according to their implantation technique (LIS vs CMS). Only centrifugal devices were included. RHF was defined as severe or severe acute RHF according to the 2013 Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) definition. Logistic multivariate regression and propensity score‒matched analyses were performed to account for confounding. RESULTS: Overall, 427 implantations occurred during the study period, with 305 patients implanted using CMS and 122 using LIS. Pre-operative extracorporeal membrane oxygenation (ECMO) and intra-aortic balloon pump (IABP) use was more common in the CMS group; off-pump implantation was more common in the LIS group. Other pre-implant variables, including age, creatinine, hemodynamics, and tricuspid regurgitation, did not differ between the 2 groups. Post-operative RHF was less common in the patients who underwent LIS than in those who underwent CMS as was post-operative right ventricular assist device (RVAD) use. LIS remained associated with less RHF in the multivariate analysis. After propensity score matching conditional for age, sex, INTERMACS profile, ECMO, and IABP use in a ratio of 2:1 (CMS to LIS), RHF (29.9% vs 18.6%, p = 0.001) and the need for post-operative RVAD (18.6% vs 8.2%; p = 0.009) remained more common in the CMS group than in the LIS group. There were no significant differences in survival up to 1 year between the groups. CONCLUSIONS: LIS may be associated with less RHF after LVAD implantation compared with CMS. Despite the possible reduction in RHF, there was no difference in 1-year survival. LIS is an alternative to traditional CMS.

Surgical Treatment of Postinfarction Ventricular Septal Rupture.

Importance: Ventricular septal rupture (VSR) is a rare but life-threatening mechanical complication of acute myocardial infarction associated with high mortality despite prompt treatment. Surgery represents the standard of care; however, only small single-center series or national registries are usually available in literature, whereas international multicenter investigations have been poorly carried out, therefore limiting the evidence on this topic. Objectives: To assess the clinical characteristics and early outcomes for patients who received surgery for postinfarction VSR and to identify factors independently associated with mortality. Design, Setting, and Participants: The Mechanical Complications of Acute Myocardial Infarction: an International Multicenter Cohort (CAUTION) Study is a retrospective multicenter international cohort study that includes patients who were treated surgically for mechanical complications of acute myocardial infarction. The study was conducted from January 2001 to December 2019 at 26 different centers worldwide among 475 consecutive patients who underwent surgery for postinfarction VSR. Exposures: Surgical treatment of postinfarction VSR, independent of the technique, alone or combined with other procedures (eg, coronary artery bypass grafting). Main Outcomes and Measures: The primary outcome was early mortality; secondary outcomes were postoperative complications. Results: Of the 475 patients included in the study, 290 (61.1%) were men, with a mean (SD) age of 68.5 (10.1) years. Cardiogenic shock was present in 213 patients (44.8%). Emergent or salvage surgery was performed in 212 cases (44.6%). The early mortality rate was 40.4% (192 patients), and it did not improve during the nearly 20 years considered for the study (median [IQR] yearly mortality, 41.7% [32.6%-50.0%]). Low cardiac output syndrome and multiorgan failure were the most common causes of death (low cardiac output syndrome, 70 [36.5%]; multiorgan failure, 53 [27.6%]). Recurrent VSR occurred in 59 participants (12.4%) but was not associated with mortality. Cardiogenic shock (survived: 95 [33.6%]; died, 118 [61.5%]; P < .001) and early surgery (time to surgery ≥7 days, survived: 105 [57.4%]; died, 47 [35.1%]; P < .001) were associated with lower survival. At multivariate analysis, older age (odds ratio [OR], 1.05; 95% CI, 1.02-1.08; P = .001), preoperative cardiac arrest (OR, 2.71; 95% CI, 1.18-6.27; P = .02) and percutaneous revascularization (OR, 1.63; 95% CI, 1.003-2.65; P = .048), and postoperative need for intra-aortic balloon pump (OR, 2.98; 95% CI, 1.46-6.09; P = .003) and extracorporeal membrane oxygenation (OR, 3.19; 95% CI, 1.30-7.38; P = .01) were independently associated with mortality. Conclusions and Relevance: In this study, surgical repair of postinfarction VSR was associated with a high risk of early mortality; this risk has remained unchanged during the last 2 decades. Delayed surgery seemed associated with better survival. Age, preoperative cardiac arrest and percutaneous revascularization, and postoperative need for intra-aortic balloon pump and extracorporeal membrane oxygenation were independently associated with early mortality. Further prospective studies addressing preoperative and perioperative patient management are warranted to hopefully improve the currently suboptimal outcome.