Right ventricular to pulmonary artery coupling in patients with different types of aortic stenosis undergoing TAVI.

BACKGROUND: Right ventricular (RV) dysfunction in patients undergoing transcatheter aortic valve implantation (TAVI) for aortic stenosis (AS) has long been disregarded. We aimed to assess the predictive value of RV to pulmonary artery coupling (RV/PAc), defined as tricuspid annular plane systolic excursion to systolic pulmonary artery pressure, on mortality in different flow types of AS after TAVI. METHODS: All patients undergoing TAVI for AS at our centre between 2018 and 2020 were assessed; 862 patients were analysed. The cohort was dichotomized using a ROC analysis (cut-off 0.512 mm/mmHg), into 429 patients with preserved and 433 patients with reduced RV/PAc. RESULTS: Reduced RV/PAc was associated with male sex and a higher rate of comorbidities. Short-term VARC-3 endpoints and NYHA classes at follow-up were comparable. Reduced RV/PAc was associated with higher 2-year all-cause mortality (35.0% [30.3-39.3%] vs. 15.4% [11.9-18.7%], hazard ratio 2.5 [1.9-3.4], p < 0.001). Cardiovascular mortality was almost tripled. Results were consistent after statistical adjustment and in a multivariate model. Sub-analyses of AS flow types revealed lower RV/PAc in classical and paradoxical low-flow low-gradient AS, with the majority having reduced RV/PAc (74% and 59%). RV/PAc retained its predictive value in these subgroups. CONCLUSIONS: RV dysfunction defined by low RV/PAc is a strong mortality predictor after TAVI independent of flow group. It should be incorporated in future TAVI risk assessment.

Mid-Term Outcome after Extracorporeal Life Support in Postcardiotomy Cardiogenic Shock: Recovery and Quality of Life.

Background: Extracorporeal life support (ECLS) therapy for refractory postcardiotomy cardiogenic shock (rPCS) is associated with high early mortality rates. This study aimed to identify negative predictors of mid-term survival and to assess health-related quality of life (HRQoL) and recovery of the survivors. Methods: Between 2017 and 2020, 142 consecutive patients received ECLS therapy following cardiac surgery. The median age was 66.0 [57.0-73.0] years, 67.6% were male and the median EuroSCORE II was 10.5% [4.2-21.3]. In 48 patients, HRQoL was examined using the 36-Item Short Form Survey (SF-36) and the modified Rankin-Scale (mRS) at a median follow-up time of 2.2 [1.9-3.2] years. Results: Estimated survival rates at 3, 12, 24 and 36 months were 47%, 46%, 43% and 43% (SE: 4%). Multivariable Cox Proportional Hazard regression analysis revealed preoperative EuroSCORE II (p = 0.013), impaired renal function (p = 0.010), cardiopulmonary bypass duration (p = 0.015) and pre-ECLS lactate levels (p = 0.004) as independent predictors of mid-term mortality. At the time of follow-up, 83.3% of the survivors were free of moderate to severe disability (mRS < 3). SF-36 analysis showed a physical component summary of 45.5 ± 10.2 and a mental component summary of 50.6 ± 12.5. Conclusions: Considering the disease to be treated, ECLS for rPCS is associated with acceptable mid-term survival, health-related quality of life and functional status. Preoperative EuroSCORE II, impaired renal function, cardiopulmonary bypass duration and lactate levels prior to ECLS implantation were identified as negative predictors and should be included in the decision-making process.

The role of coronary artery disease in lung transplantation: a propensity-matched analysis.

BACKGROUND AND AIMS: Candidate selection for lung transplantation (LuTx) is pivotal to ensure individual patient benefit as well as optimal donor organ allocation. The impact of coronary artery disease (CAD) on post-transplant outcomes remains controversial. We provide comprehensive data on the relevance of CAD for short- and long-term outcomes following LuTx and identify risk factors for mortality. METHODS: We retrospectively analyzed all adult patients (≥ 18 years) undergoing primary and isolated LuTx between January 2000 and August 2021 at the LMU University Hospital transplant center. Using 1:1 propensity score matching, 98 corresponding pairs of LuTx patients with and without relevant CAD were identified. RESULTS: Among 1,003 patients having undergone LuTx, 104 (10.4%) had relevant CAD at baseline. There were no significant differences in in-hospital mortality (8.2% vs. 8.2%, p > 0.999) as well as overall survival (HR 0.90, 95%CI [0.61, 1.32], p = 0.800) between matched CAD and non-CAD patients. Similarly, cardiovascular events such as myocardial infarction (7.1% CAD vs. 2.0% non-CAD, p = 0.170), revascularization by percutaneous coronary intervention (5.1% vs. 1.0%, p = 0.212), and stroke (2.0% vs. 6.1%, p = 0.279), did not differ statistically between both matched groups. 7.1% in the CAD group and 2.0% in the non-CAD group (p = 0.078) died from cardiovascular causes. Cox regression analysis identified age at transplantation (HR 1.02, 95%CI [1.01, 1.04], p < 0.001), elevated bilirubin (HR 1.33, 95%CI [1.15, 1.54], p < 0.001), obstructive lung disease (HR 1.43, 95%CI [1.01, 2.02], p = 0.041), decreased forced vital capacity (HR 0.99, 95%CI [0.99, 1.00], p = 0.042), necessity of reoperation (HR 3.51, 95%CI [2.97, 4.14], p < 0.001) and early transplantation time (HR 0.97, 95%CI [0.95, 0.99], p = 0.001) as risk factors for all-cause mortality, but not relevant CAD (HR 0.96, 95%CI [0.71, 1.29], p = 0.788). Double lung transplant was associated with lower all-cause mortality (HR 0.65, 95%CI [0.52, 0.80], p < 0.001), but higher in-hospital mortality (OR 2.04, 95%CI [1.04, 4.01], p = 0.039). CONCLUSION: In this cohort, relevant CAD was not associated with worse outcomes and should therefore not be considered a contraindication for LuTx. Nonetheless, cardiovascular events in CAD patients highlight the necessity of control of cardiovascular risk factors and a structured cardiac follow-up.

Aortic arch blood flow measurements as a predictor of successful ECMO weaning in cardiogenic shock.

Objective: Acute cardiogenic shock is a life-threatening condition with mortality rates of up to 50%. If conventional therapy fails, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) therapy has emerged to a promising alternative for temporary cardiac and respiratory support in specialized centers. However, it is only a bridge to recovery, final decision, heart transplantation or the permanent implantation of a left ventricular assist device. Therefore, the identification of the optimum weaning time point is challenging, and standardized weaning protocols are rare. Methods: In this explorative pilot study, we evaluated the potential benefit of blood flow measurements in the aortic arch using an ultrasonic cardiac output monitor (USCOM) for the primary endpoint of successful VA-ECMO weaning. 12 patients under VA-ECMO therapy for acute cardiogenic shock and a hemodynamic condition which qualified for a stepwise weaning process were included in this study. Main exclusion criterion was the presence of additional venting therapy for left ventricular unloading, e.g. Impella. Statistical comparisons were performed using the Mann-Whitney test and corrected for multiple testing by the Holm-Sidak method. Results: Peak velocity of flow in the aortic arch showed a positive correlation with weaning success independent of ECMO flow (weaning success vs. failure: 0.75 vs. 0.35 m/s (low ECMO support), p = 0.049), whereas we identified only a trend for mean pressure gradient, minute distance and stroke volume index. Conclusion: We hypothesize, that USCOM might provide an additive benefit to conventional strategies in its ability to predict successful VA-ECMO weaning and prevent pulmonary congestion. Larger upcoming trials are required to address this relevant topic and provide standardized treatment protocols for optimized weaning in the future.

Scrutinizing the Role of Venoarterial Extracorporeal Membrane Oxygenation: Has Clinical Practice Outpaced the Evidence?

The use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) for temporary mechanical circulatory support in various clinical scenarios has been increasing consistently, despite the lack of sufficient evidence regarding its benefit and safety from adequately powered randomized controlled trials. Although the ARREST trial (Advanced Reperfusion Strategies for Patients with Out-of-Hospital Cardiac Arrest and Refractory Ventricular Fibrillation) and a secondary analysis of the PRAGUE OHCA trial (Prague Out-of-Hospital Cardiac Arrest) provided some evidence in favor of VA-ECMO in the setting of out-of-hospital cardiac arrest, the INCEPTION trial (Early Initiation of Extracorporeal Life Support in Refractory Out-of-Hospital Cardiac Arrest) has not found a relevant improvement of short-term mortality with extracorporeal cardiopulmonary resuscitation. In addition, the results of the recently published ECLS-SHOCK trial (Extracorporeal Life Support in Cardiogenic Shock) and ECMO-CS trial (Extracorporeal Membrane Oxygenation in the Therapy of Cardiogenic Shock) discourage the routine use of VA-ECMO in patients with infarct-related cardiogenic shock. Ongoing clinical trials (ANCHOR [Assessment of ECMO in Acute Myocardial Infarction Cardiogenic Shock, NCT04184635], REVERSE [Impella CP With VA ECMO for Cardiogenic Shock, NCT03431467], UNLOAD ECMO [Left Ventricular Unloading to Improve Outcome in Cardiogenic Shock Patients on VA-ECMO, NCT05577195], PIONEER [Hemodynamic Support With ECMO and IABP in Elective Complex High-risk PCI, NCT04045873]) may clarify the usefulness of VA-ECMO in specific patient subpopulations and the efficacy of combined mechanical circulatory support strategies. Pending further data to refine patient selection and management recommendations for VA-ECMO, it remains uncertain whether the present usage of this device improves outcomes.

Sex-related differences in patients presenting with heart failure-related cardiogenic shock.

BACKGROUND: Heart failure-related cardiogenic shock (HF-CS) accounts for a significant proportion of all CS cases. Nevertheless, there is a lack of evidence on sex-related differences in HF-CS, especially regarding use of treatment and mortality risk in women vs. men. This study aimed to investigate potential differences in clinical presentation, use of treatments, and mortality between women and men with HF-CS. METHODS: In this international observational study, patients with HF-CS (without acute myocardial infarction) from 16 tertiary-care centers in five countries were enrolled between 2010 and 2021. Logistic and Cox regression models were used to assess differences in clinical presentation, use of treatments, and 30-day mortality in women vs. men with HF-CS. RESULTS: N = 1030 patients with HF-CS were analyzed, of whom 290 (28.2%) were women. Compared to men, women were more likely to be older, less likely to have a known history of heart failure or cardiovascular risk factors, and lower rates of highly depressed left ventricular ejection fraction and renal dysfunction. Nevertheless, CS severity as well as use of treatments were comparable, and female sex was not independently associated with 30-day mortality (53.0% vs. 50.8%; adjusted HR 0.94, 95% CI 0.75-1.19). CONCLUSIONS: In this large HF-CS registry, sex disparities in risk factors and clinical presentation were observed. Despite these differences, the use of treatments was comparable, and both sexes exhibited similarly high mortality rates. Further research is necessary to evaluate if sex-tailored treatment, accounting for the differences in cardiovascular risk factors and clinical presentation, might improve outcomes in HF-CS.

The association of off-hour vs. on-hour intensive care unit admission time with mortality in patients with cardiogenic shock: a retrospective multi-centre analysis.

AIMS: Studies have shown a so-called off-hour effect for many different diseases, but data are scarce concerning cardiogenic shock. We therefore assessed the association of off-hour vs. on-hour intensive care unit admission with 30-day mortality in patients with cardiogenic shock. METHODS AND RESULTS: In total, 1720 cardiogenic shock patients (666 admitted during off-hours) from two large university hospitals in Germany were included in retrospect. An admission during off-hours was associated with increased 30-day mortality compared to an admission during on-hours [crude mortality 48% vs. 41%, HR 1.17 (1.03-1.33), P = 0.017]. This effect remained significant after propensity score matching (P = 0.023). Neither patients with a combined SCAI stage D and E (P = 0.088) or C (P = 0.548) nor those requiring cardiopulmonary resuscitation (P = 0.114) had a higher mortality at off-hour admission. In contrast, those without veno-arterial extracorporeal membrane oxygenation [HR 1.17 (1.00-1.36), P = 0.049], without acute myocardial infarction [HR 1.27 (1.02-1.56), P = 0.029] or a with combined SCAI stage A and B [HR 2.23 (1.08-4.57), P = 0.025] had an increased mortality at off-hour admission. CONCLUSION: Our study showed an increased mortality in patients with cardiogenic shock admitted during off-hours, especially in those with a milder onset of disease. This stresses the importance of a thorough workup of each patient, especially at times of limited resources, the menace of underestimating the severity of cardiogenic shock, and the need for an improved 24×7 available risk stratification.

Atrial Functional Tricuspid Regurgitation in Patients Undergoing Transcatheter Aortic Valve Replacement.

BACKGROUND: Knowledge about atrial functional tricuspid regurgitation (afTR) in transcatheter aortic valve replacement (TAVR) patients is scarce. OBJECTIVES: The aim of the study was to analyze the association between the entity and the development of tricuspid regurgitation (TR) in patients undergoing TAVR for aortic stenosis and concomitant TR. METHODS: We analyzed patients undergoing TAVR for severe aortic stenosis from January 2013 to December 2020 and concomitant at least moderate TR at baseline. afTR was defined as enlargement of the right atrium in relation to the right ventricle. TR development after TAVR and 3-year all-cause mortality were evaluated. RESULTS: Out of 3,474 TAVR patients, we identified 420 patients with concomitant at least moderate TR. A total of 363 patients were included in the study, with 178 patients stratified in the afTR and 185 in the non-afTR group based on a receiver-operating characteristic curve cutoff of 1.132 of the right atrial/right ventricular area ratio. TR improvement after TAVR was observed in significantly less patients with afTR compared with non-afTR (31.1% vs 60.6%; P < 0.001). Multivariate regression analysis confirmed afTR as independent predictor for TR persistence (adjusted OR: 2.80; 95% CI: 1.66-4.76; P < 0.001). Moreover, afTR was associated with aggravation of TR after TAVR (17.0% vs 6.8%; P = 0.013). Three-year all-cause mortality was significantly higher in patients with persistence compared with patients with improvement of TR (P < 0.001). CONCLUSIONS: In TAVR patients, afTR is an independent predictor for TR persistence. Moreover, TR persistence is associated with increased 3-year all-cause mortality.

Clinical presentation, shock severity and mortality in patients with de novo versus acute-on-chronic heart failure-related cardiogenic shock.

AIMS: Heart failure-related cardiogenic shock (HF-CS) accounts for a significant proportion of CS cases. Whether patients with de novo HF and those with acute-on-chronic HF in CS differ in clinical characteristics and outcome remains unclear. The aim of this study was to evaluate differences in clinical presentation and mortality between patients with de novo and acute-on-chronic HF-CS. METHODS AND RESULTS: In this international observational study, patients with HF-CS from 16 tertiary care centres in five countries were enrolled between 2010 and 2021. To investigate differences in clinical presentation and 30-day mortality, adjusted logistic/Cox regression models were fitted. Patients (n = 1030) with HF-CS were analysed, of whom 486 (47.2%) presented with de novo HF-CS and 544 (52.8%) with acute-on-chronic HF-CS. Traditional markers of CS severity (e.g. blood pressure, heart rate and lactate) as well as use of treatments were comparable between groups. However, patients with acute-on-chronic HF-CS were more likely to have a higher CS severity and also a higher mortality risk, after adjusting for relevant confounders (de novo HF 45.5%, acute-on-chronic HF 55.9%, adjusted hazard ratio 1.38, 95% confidence interval 1.10-1.72, p = 0.005). CONCLUSION: In this large HF-CS cohort, acute-on-chronic HF-CS was associated with more severe CS and higher mortality risk compared to de novo HF-CS, although traditional markers of CS severity and use of treatments were comparable. These findings highlight the vast heterogeneity of patients with HF-CS, emphasize that HF chronicity is a relevant disease modifier in CS, and indicate that future clinical trials should account for this.

Complications in patients with cardiogenic shock on veno-arterial extracorporeal membrane oxygenation therapy: distribution and relevance. Results from an international, multicentre cohort study.

AIMS: Veno-arterial extracorporeal membrane oxygenation therapy (VA-ECMO) restores circulation and tissue oxygenation in cardiogenic shock (CS) patients, but can also lead to complications. This study aimed to quantify VA-ECMO complications and analyse their association with overall survival as well as favourable neurological outcome (cerebral performance categories 1 + 2). METHODS AND RESULTS: All-comer patients with CS treated with VA-ECMO were retrospectively enrolled from 16 centres in four countries (2005-2019). Neurological, bleeding, and ischaemic adverse events (AEs) were considered. From these, typical VA-ECMO complications were identified and analysed separately as device-related complications. n = 501. Overall, 118 were women (24%), median age was 56.0 years, median lactate was 8.1 mmol/L. Acute myocardial infarction caused CS in 289 patients (58%). Thirty-days mortality was 40% (198/501 patients). At least one device-related complication occurred in 252/486 (52%) patients, neurological AEs in 108/469 (23%), bleeding in 192/480 (40%), ischaemic AEs in 123/478 (26%). The 22% of patients with the most AEs accounted for 50% of all AEs. All types of AEs were associated with a worse prognosis. Aside from neurological ones, all AEs and device-related complications were more likely to occur in women; although prediction of AEs outside of neurological AEs was generally poor. CONCLUSION: Therapy and device-related complications occur in half of all patients treated with VA-ECMO and are associated with a worse prognosis. They accumulate in some patients, especially in women. Aside from neurological events, identification of patients at risk is difficult, highlighting the need to establish additional quantitative markers of complication risk to guide VA-ECMO treatment in CS.

Association between left ventricular ejection fraction, mortality and use of mechanical circulatory support in patients with non-ischaemic cardiogenic shock.

BACKGROUND: Currently, use of mechanical circulatory support (MCS) in non-ischaemic cardiogenic shock (CS) is predominantly guided by shock-specific markers, and not by markers of cardiac function. We hypothesise that left ventricular ejection fraction (LVEF) can identify patients with a higher likelihood to benefit from MCS and thus help to optimise their expected benefit. METHODS: Patients with non-ischaemic CS and available data on LVEF from 16 tertiary-care centres in five countries were analysed. Cox regression models were fitted to evaluate the association between LVEF and mortality, as well as the interaction between LVEF, MCS use and mortality. RESULTS: N = 807 patients were analysed: mean age 63 [interquartile range (IQR) 51.5-72.0] years, 601 (74.5%) male, lactate 4.9 (IQR 2.6-8.5) mmol/l, LVEF 20 (IQR 15-30) %. Lower LVEF was more frequent amongst patients with more severe CS, and MCS was more likely used in patients with lower LVEF. There was no association between LVEF and 30-day mortality risk in the overall study cohort. However, there was a significant interaction between MCS use and LVEF, indicating a lower 30-day mortality risk with MCS use in patients with LVEF ≤ 20% (hazard ratio 0.72, 95% confidence interval 0.51-1.02 for LVEF ≤ 20% vs. hazard ratio 1.31, 95% confidence interval 0.85-2.01 for LVEF > 20%, interaction-p = 0.017). CONCLUSION: This retrospective study may indicate a lower mortality risk with MCS use only in patients with severely reduced LVEF. This may propose the inclusion of LVEF as an adjunctive parameter for MCS decision-making in non-ischaemic CS, aiming to optimise the benefit-risk ratio.

Heparin dosing in patients with Impella-supported cardiogenic shock.

BACKGROUND: Impella™ is increasingly used in cardiogenic shock. However, thromboembolic and bleeding events are frequent during percutaneous mechanical circulatory support (pMCS). OBJECTIVE: Therefore, we aimed to explore the optimal anticoagulation regime for pMCS to prevent thromboembolism and bleedings. METHODS: This hypothesis-generating multi-center cohort study investigated 170 patients with left-Impella™ support. We (A) compared bleeding/thrombotic events in two centers with therapeutic range (TR-aPTT) activated partial thromboplastin time (60-80s) and (B) compared events of these centers with one center with intermediate range aPTT (40-60s). RESULTS: After matching, there were no differences in patients' characteristics. In centers aiming at TR-aPTT, major bleeding was numerically lower with aPTT <60s within 48 h of left-Impella™ support, versus patients that achieved the aimed aPTT of ≥60s [aPTT ≥60s: 22 (37.3%) vs. aPTT<60s 14 (23.7%); Hazard ratio [HR], 0.62 (95%) CI, 0.28-1.38; p = 0.234]. Major cardiovascular and cerebrovascular adverse events (MACCE) did not differ between groups. In comparison of centers, TR-aPTT strategy showed higher major bleeding rates [TR: 8 (47.1%) vs. intermediate range: 1 (5.9%); HR, 0.06 (95%) CI, 0.01-0.45; p = 0.006]. MACCE were lower in the intermediate range aPTT group as well [TR 12 (70.6%) vs. intermediate range 5 (29.4%) HR, 0.32 (95%) CI, 0.11-0.92; p = 0.034]. CONCLUSION: This pilot analysis showed that lowering UFH-targets in left-Impella™ supported CS patients seems to be a safe and promising strategy for reducing major bleedings without increasing MACCE. This needs to be validated in larger, randomized clinical trials.

Concomitant percutaneous coronary intervention in patients undergoing transcatheter aortic valve implantation.

BACKGROUND: Patients undergoing transcatheter aortic valve implantation (TAVI) frequently have coronary artery disease requiring percutaneous coronary intervention (PCI). Usually, PCI and TAVI are performed in two separate procedures and current studies are investigating potential benefits regarding the order. However, the two interventions may also be performed simultaneously, thereby limiting the risk associated with repeated vascular access. Data evaluating benefit and harm of concomitant procedures are scarce. AIMS: Therefore, this study aimed to evaluate concomitant PCI (coPCI) in TAVI patients regarding Valve Academic Research Consortium 3 (VARC-3) endpoints and long-term mortality. METHODS: A total of 2233 consecutive TAVI patients from the EVERY-VALVE registry were analyzed according to the VARC-3 endpoint definitions. A total of 274 patients had undergone TAVI and concomitant PCI (coPCI group). They were compared to 226 TAVI patients who had received PCI within 60 days before TAVI in a stepwise approach (swPCI group) and to the remaining 1733 TAVI patients who had not undergone PCI recently (noPCI group). RESULTS: Overall median age was 81.4 years, median Society of Thoracic Surgeons score was 4.0%. Patients in the coPCI and in the swPCI group were predominantly male with reduced left-ventricular ejection fraction. Rates of VARC-3 composite endpoints technical success and 30-day device success were comparable between all three groups. Mortality rates at 3 years after TAVI were similar (coPCI, 34.2% vs. swPCI, 31.9% vs. noPCI, 34.0% p = 0.84). CONCLUSIONS: coPCI during TAVI seems comparable in a retrospective analysis. Compared to a stepwise approach, it has similar rates of composite endpoints technical success and device success as well as long-term mortality.

Comparison of balanced and unbalanced crystalloids as resuscitation fluid in patients treated for cardiogenic shock.

BACKGROUND: The efficacy and safety of saline versus balanced crystalloid solutions in ICU-patients remains complicated by exceptionally heterogenous study population in past comparative studies. This study sought to compare saline and balanced crystalloids for fluid resuscitation in patients with cardiogenic shock with or without out-of-hospital cardiac arrest (OHCA). METHODS: We retrospectively analyzed 1032 propensity score matched patients with cardiogenic shock from the Munich University Hospital from 2010 to 2022. In 2018, default resuscitation fluid was changed from 0.9% saline to balanced crystalloids. The primary endpoint was defined as 30-day mortality rate. RESULTS: Patients in the saline group (n = 516) had a similar 30-day mortality rate as patients treated with balanced crystalloids (n = 516) (43.1% vs. 43.0%, p = 0.833), but a higher incidence of new onset renal replacement therapy (30.2% vs 22.7%, p = 0.007) and significantly higher doses of catecholamines. However, OHCA-patients with a lactate level higher than 7.4 mmol/L had a significantly lower 30-day mortality rate when treated with saline (58.6% vs. 79.3%, p = 0.013). In addition, use of balanced crystalloids was independently associated with a higher mortality in the multivariate cox regression analysis after OHCA (hazard ratio 1.43, confidence interval: 1.05-1.96, p = 0.024). CONCLUSIONS: In patients with cardiogenic shock, use of balanced crystalloids was associated with a similar all-cause mortality at 30 days but a lower rate of new onset of renal replacement therapy. In the subgroup of patients after OHCA with severe shock, use of balanced crystalloids was associated with a higher mortality than saline. TRIAL REGISTRATION: LMUshock registry (WHO International Clinical Trials Registry Platform Number DRKS00015860).

Venoarterial extracorporeal membrane oxygenation or standard care in patients with cardiogenic shock complicating acute myocardial infarction: the multicentre, randomised EURO SHOCK trial.

BACKGROUND: Cardiogenic shock (CGS) occurs in 10% of patients presenting with acute myocardial infarction (MI), with in-hospital mortality rates of 40-50% despite revascularisation. AIMS: The EURO SHOCK trial aimed to determine if early use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) could improve outcomes in patients with persistent CGS following primary percutaneous coronary intervention (PPCI). METHODS: This multicentre, pan-European trial randomised patients with persistent CGS 30 minutes after PPCI of the culprit lesion to receive either VA-ECMO or continue with standard therapy. The primary outcome measure was 30-day all-cause mortality in an intention-to-treat analysis. Secondary endpoints included 12-month all-cause mortality and 12-month composite of all-cause mortality or rehospitalisation due to heart failure. RESULTS: Due to the impact of the COVID-19 pandemic, the trial was stopped before completion of recruitment, after randomisation of 35 patients (standard therapy n=18, VA-ECMO n=17). Thirty-day all-cause mortality occurred in 43.8% of patients randomised to VA-ECMO and in 61.1% of patients randomised to standard therapy (hazard ratio [HR] 0.56, 95% confidence interval [CI]: 0.21-1.45; p=0.22). One-year all-cause mortality was 51.8% in the VA-ECMO group and 81.5% in the standard therapy arm (HR 0.52, 95% CI: 0.21-1.26; p=0.14). Vascular and bleeding complications occurred more often in the VA-ECMO arm (21.4% vs 0% and 35.7% vs 5.6%, respectively). CONCLUSIONS: Due to the limited number of patients recruited to the trial, no definite conclusions could be drawn from the available data. Our study demonstrates the feasibility of randomising patients with CGS complicating acute MI but also illustrates the challenges. We hope these data will inspire and inform the design of future large-scale trials.

Cardio-hepatic syndrome in patients undergoing transcatheter aortic valve replacement.

BACKGROUND: Cardiohepatic syndrome (CHS) has been identified as an important but underrecognized survival predictor in multiple cardiovascular disease entities. The objectives of this study were to evaluate the prevalence and prognostic value of CHS in patients undergoing TAVR for severe aortic stenosis (AS). METHODS: The study included patients with available laboratory parameters of hepatic function who underwent TAVR from July 2013 until December 2019 at our center. CHS was defined as an elevation of at least two of three laboratory cholestasis parameters above the upper limit of normal (bilirubin, alkaline phosphatase, and gamma glutamyl transferase). Study endpoints were three-year survival, technical and device failure (VARC 3), as well as New York Heart Association (NYHA) functional class at follow-up. RESULTS: Among a total of 953 analyzed patients (47.6% females, median age 80.0 [76.0-85.0] years) CHS was present in 212 patients (22.4%). In patients with vs. without CHS, rates of technical (6.1% vs. 8.4%, p = 0.29) and device failure (18.9% vs. 17.3%, p = 0.59) were comparable. NYHA functional class at baseline and follow-up was more severe in patients with CHS. Nevertheless, heart failure symptoms improved from baseline to follow-up irrespective of hepatic function. Three-year survival rates were significantly lower in patients with CHS (49.4 vs. 65.4%, p < 0.001). The predictive value of CHS persisted after adjustment in a multivariable analysis (hazard ratio 1.58, p < 0.01). CONCLUSION: In patients undergoing TAVR, CHS is prevalent in 22% of patients and is associated with increased postinterventional mortality. Thus, CHS should be included in the decision-making process within the TAVR heart team. Cardiohepatic syndrome (CHS) as defined by an elevation of at least two of three laboratory cholestasis parameters above the upper limit of normal was prevalent in 22% of patients undergoing TAVR for severe AS. The presence of CHS was associated with more severe heart failure symptoms and worse three-year survival.

Impact of mitral regurgitation aetiology on the outcomes of transcatheter aortic valve implantation.

BACKGROUND: Concomitant moderate/severe mitral regurgitation (MR) is observed in 17-35% of patients undergoing transcatheter aortic valve implantation (TAVI) and contributes to a worse prognosis. Studies analysing outcomes in patients undergoing TAVI with different MR aetiologies, including atrial functional MR (aFMR), are lacking. AIMS: We aimed to analyse outcomes and changes in MR severity in patients with aFMR, ventricular functional (vFMR) and primary mitral regurgitation (PMR) following TAVI. METHODS: We analysed all consecutive patients with at least moderate MR undergoing TAVI between January 2013 and December 2020 at the Munich University Hospital. Characterisation of MR aetiology was performed by detailed individual echocardiographic assessment. Three-year mortality, changes in MR severity and New York Heart Association (NYHA) Functional Class at follow-up were assessed. RESULTS: Out of 3,474 patients undergoing TAVI, 631 patients showed MR ≥2+ (172 with aFMR, 296 with vFMR, 163 with PMR). Procedural characteristics and endpoints were comparable between groups. The rate of MR improvement was 80.2% in aFMR patients, which was significantly higher compared to both other groups (vFMR: 69.4%; p=0.03; PMR: 40.8%; p<0.001). The estimated 3-year survival rates did not differ between aetiologies (p=0.57). However, MR persistence at follow-up was associated with increased mortality (hazard ratio 1.49, 95% confidence interval: 1.04-2.11; p=0.027), mainly driven by the PMR subgroup of patients. NYHA Class improved significantly in all groups. In patients with baseline MR ≥3+, the PMR aetiology was associated with the lowest MR improvement, the lowest survival rates and least symptomatic improvement. CONCLUSIONS: TAVI reduces MR severity and symptoms in patients with aFMR, vFMR and less-pronounced PMR. The presence of aFMR was associated with the greatest MR severity improvement.

Immobility-associated thromboprotection is conserved across mammalian species from bear to human.

Venous thromboembolism (VTE) comprising deep venous thrombosis and pulmonary embolism is a major cause of morbidity and mortality. Short-term immobility-related conditions are a major risk factor for the development of VTE. Paradoxically, long-term immobilized free-ranging hibernating brown bears and paralyzed spinal cord injury (SCI) patients are protected from VTE. We aimed to identify mechanisms of immobility-associated VTE protection in a cross-species approach. Mass spectrometry-based proteomics revealed an antithrombotic signature in platelets of hibernating brown bears with heat shock protein 47 (HSP47) as the most substantially reduced protein. HSP47 down-regulation or ablation attenuated immune cell activation and neutrophil extracellular trap formation, contributing to thromboprotection in bears, SCI patients, and mice. This cross-species conserved platelet signature may give rise to antithrombotic therapeutics and prognostic markers beyond immobility-associated VTE.

Cardio-hepatic syndrome in patients undergoing mitral valve transcatheter edge-to-edge repair.

AIMS: The impact of the cardio-hepatic syndrome (CHS) on outcomes in patients undergoing mitral valve transcatheter edge-to-edge repair (M-TEER) for relevant mitral regurgitation (MR) is unknown. The objectives of this study were three-fold: (i) to characterize the pattern of hepatic impairment, (ii) to investigate the prognostic value of CHS, and (iii) to evaluate the changes in hepatic function after M-TEER. METHODS AND RESULTS: Hepatic impairment was quantified by laboratory parameters of liver function. In accordance with existing literature, two types of CHS were distinguished: ischaemic type I CHS (elevation of both transaminases) and cholestatic type II CHS (elevation of two out of three parameters of hepatic cholestasis). The impact of CHS on 2-year mortality was evaluated using a Cox model. The change in hepatic function after M-TEER was assessed by laboratory testing at follow-up. We analysed 1083 patients who underwent M-TEER for relevant primary or secondary MR at four European centres between 2008 and 2019. Ischaemic type I and cholestatic type II CHS were observed in 11.1% and 23.0% of patients, respectively. Predictors for 2-year all-cause mortality differed by MR aetiology. While in primary MR cholestatic type II CHS was independently associated with 2-year mortality, ischaemic CHS type I was an independent mortality predictor in secondary MR patients. At follow-up, patients with MR reduction ≤2+ (obtained in 90.7% of patients) presented with improved parameters of hepatic function (median reduction of 0.2 mg/dl, 0.2 U/L and 21 U/L for bilirubin, alanine aminotransferase and gamma-glutamyl transferase, respectively, p < 0.01). CONCLUSIONS: The CHS is frequently observed in patients undergoing M-TEER and significantly impairs 2-year survival. Successful M-TEER may have beneficial effects on CHS.

Indocyanine green clearance predicts outcome in patients undergoing transcatheter valve intervention for severe atrio-ventricular valve regurgitation.

OBJECTIVES: Severe mitral regurgitation (MR) and tricuspid regurgitation (TR) aggravate haemodynamic stress leading to congestive heart failure with impaired hepatic function, also known as cardiohepatic syndrome (CHS). Current perioperative risk calculators do not sufficiently consider CHS and serum liver function parameters lack sensitivity to diagnose CHS. Indocyanine green and its elimination (measured by the LIMON® test) represent a dynamic and non-invasive test which correlates with the hepatic function. Nevertheless, its utility in the setting of transcatheter valve repair/replacement (TVR) to predict CHS and outcome remains unknown. METHODS: We analysed liver function and outcomes of patients undergoing TVR for MR or TR between August 2020 and May 2021 at the Munich University Hospital. RESULTS: Out of a total of 44 patients treated at the University Hospital of Munich, 21 (48%) were treated for severe MR, 20 (46%) for severe TR and 3 (7%) for both diseases. Procedural success defined as MR/TR ≤2+ was 94% among MR patients and 92% among TR patients. While classical serum liver function parameters did not change after TVR, there was a significant improvement in liver function as assessed by the LIMON® test (P ≤ 0.001). Patients with baseline indocyanine green plasma disappearance rate <12.95%/min showed significantly increased 1-year mortality (hazard ratio: 1.54, 95% confidence interval: 1.05-2.25, P = 0.027) and lower New York Hear Association class improvement (P = 0.05). CONCLUSIONS: Especially in the context of the recently stressed importance of a careful patient selection prior to the interdisciplinary treatment of valvular heart disease, the LIMON® test may provide further real-time information on the patients' cardiohepatic injury and prognosis.