Early goal-directed management after out-of-hospital cardiac arrest: lessons from a certified cardiac Arrest centre.

BACKGROUND: Despite continuous advances in post-resuscitation management, outcome after out-of-hospital cardiac arrest (OHCA) is limited. To improve the outcome, interdisciplinary Cardiac Arrest Centers (CACs) have been established in recent years, but survival remains low and treatment strategies vary considerably in clinical and geographical aspects. Here we analyzed a strategy of in-hospital post-resuscitation management while evaluating the outcome. METHODS: A broad spectrum of pre- and in-hospital parameters of 545 resuscitated patients, admitted to the Cardiac Arrest Center of the University Hospital of Marburg (MCAC) between 01/2018 and 12/2022 were retrospectively analyzed. Inclusion criteria were ≥ 18 years, resuscitation by emergency medical services, and non-traumatic cause of OHCA. RESULTS: In the overall patient cohort, the survival rate to hospital discharge was 39.8% (n = 217/545), which is 50.7% higher than in the EuReCa-TWO registry. 77.2% of the survivors had CPC status 1 or 2 (favorable neurological outcome) before and after therapy. A standardized 'therapy bundle' for in-hospital post-resuscitation management was applied to 445 patients who survived the initial treatment in the emergency department. In addition to basic care (standardized antimicrobial therapy, adequate anticoagulation, targeted sedation, early enteral and parenteral nutrition), it includes early whole-body CT (n = 391; 87.9%), invasive coronary diagnostics (n = 322; 72.4%), targeted temperature management (n = 293; 65.8%) and if indicated, mechanical circulatory support (n = 145; 32.6%) and appropriate neurological diagnostics. CONCLUSIONS: Early goal-directed post-resuscitation management in a well-established and highly frequented CAC leads to significantly higher survival rates. However, our results underline the need for a broader standardization in post-resuscitation management to ultimately improve the outcome.

Monitoring a Mystery: The Unknown Right Ventricle during Left Ventricular Unloading with Impella in Patients with Cardiogenic Shock.

Background: Right ventricular (RV) dysfunction or failure occurs in more than 30% of patients in cardiogenic shock (CS). However, the importance of timely diagnosis of prognostically relevant impairment of RV function is often underestimated. Moreover, data regarding the impact of mechanical circulatory support like the Impella on RV function are rare. Here, we investigated the effects of the left ventricular (LV) Impella on RV function. Moreover, we aimed to identify the most optimal and the earliest applicable parameter for bedside monitoring of RV function by comparing the predictive abilities of three common RV function parameters: the pulmonary artery pulsatility index (PAPi), the ratio of right atrial pressure to pulmonary capillary wedge pressure (RA/PCWP), and the right ventricular stroke work index (RVSWI). Methods: The data of 50 patients with CS complicating myocardial infarction, supported with different flow levels of LV Impella, were retrospectively analyzed. Results: Enhancing Impella flow (1.5 to 2.5 L/min ± 0.4 L/min) did not lead to a significant variation in PAPi (p = 0.717), RA/PCWP (p = 0.601), or RVSWI (p = 0.608), indicating no additional burden for the RV. PAPi revealed the best ability to connect RV function with global hemodynamic parameters, i.e., cardiac index (CI; p < 0.001, 95% CI: 0.181-0.663), pulmonary capillary wedge pressure (PCWP; p = 0.005, 95% CI: -6.721--1.26), central venous pressure (CVP; p < 0.001, 95% CI: -7.89-5.575), and indicators of tissue perfusion (central venous oxygen saturation (SvO2); p = 0.008, 95% CI: 1.096-7.196). Conclusions: LV Impella does not impair RV function. Moreover, PAPi seems to be to the most effective and valid predictor for early bedside monitoring of RV function.

Discussion of hemodynamic optimization strategies and the canonical understanding of hemodynamics during biventricular mechanical support in cardiogenic shock: does the flow balance make the difference?

BACKGROUND: Mechanical circulatory support (MCS) devices may stabilize patients with severe cardiogenic shock (CS) following myocardial infarction (MI). However, the canonical understanding of hemodynamics related to the determination of the native cardiac output (CO) does not explain or support the understanding of combined left and right MCS. To ensure the most optimal therapy control, the current principles of hemodynamic measurements during biventricular support should be re-evaluated. METHODS: Here we report a protocol of hemodynamic optimization strategy during biventricular MCS (VA-ECMO and left ventricular Impella) in a case series of 10 consecutive patients with severe cardiogenic shock complicating myocardial infarction. During the protocol, the flow rates of both devices were switched in opposing directions (+ / - 0.7 l/min) for specified times. To address the limitations of existing hemodynamic measurement strategies during biventricular support, different measurement techniques (thermodilution, Fick principle, mixed venous oxygen saturation) were performed by pulmonary artery catheterization. Additionally, Doppler ultrasound was performed to determine the renal resistive index (RRI) as an indicator of renal perfusion. RESULTS: The comparison between condition 1 (ECMO flow > Impella flow) and condition 2 (Impella flow > VA-ECMO flow) revealed significant changes in hemodynamics. In detail, compared to condition 1, condition 2 results in a significant increase in cardiac output (3.86 ± 1.11 vs. 5.44 ± 1.13 l/min, p = 0.005) and cardiac index (2.04 ± 0.64 vs. 2.85 ± 0.69, p = 0.013), and mixed venous oxygen saturation (56.44 ± 6.97% vs. 62.02 ± 5.64% p = 0.049), whereas systemic vascular resistance decreased from 1618 ± 337 to 1086 ± 306 s*cm-5 (p = 0.002). Similarly, RRI decreased in condition 2 (0.662 ± 0.05 vs. 0.578 ± 0.06, p = 0.003). CONCLUSIONS: To monitor and optimize MCS in CS, PA catheterization for hemodynamic measurement is applicable. Higher Impella flow is superior to higher VA-ECMO flow resulting in a more profound increase in CO with subsequent improvement of organ perfusion.

New-Onset Atrial Fibrillation in the Setting of COVID-19 Infection Is a Predictor of Mortality in Hospitalized Patients: CovAF-Study.

Recent studies show that hospitalized COVID-19 patients have an increased incidence of arrhythmia, especially atrial fibrillation (AF). This single-center study included 383 hospitalized patients with positive polymerase chain reaction tests for COVID-19 from March 2020 to April 2021. Patient characteristics were documented, and data were analyzed for episodes of AF on admission or during the hospital stay, intrahospital mortality, need for intensive care and/or invasive ventilation, inflammatory parameters (hs-CRP, IL-6, and procalcitonin), and differential blood count. We demonstrated that in the setting of hospitalized cases of COVID-19 infection, there is an incidence of 9.8% (n = 36) for the occurrence of new-onset AF. Furthermore, it was shown that a total of 21% (n = 77) had a history of episodes of paroxysmal/persistent AF. However, only about one-third of patients with pre-existing AF had relevant documented tachycardic episodes during the hospital stay. Patients with new-onset AF had a significantly increased intrahospital mortality compared to the control and the pre-existing AF without rapid ventricular rate (RVR) group. Patients with new-onset AF required intensive care and invasive ventilation more frequently. Further analysis examined patients with episodes of RVR and demonstrated that they had significantly elevated CRP (p < 0.05) and PCT (p < 0.05) levels on the day of hospital admission compared to patients without RVR.

The Impact of Positive Inotropic Therapy on Hemodynamics and Organ Function in Acute Heart Failure: A Differentiated View.

BACKGROUND: Little is known about the impact of treatment with inotropic drugs on the interaction of hemodynamics, biomarkers, and end-organ function in patients with acute decompensated heart failure (HF) of different origins and heart rhythms. METHODS: Fifty patients with different causes of acute decompensated HF (dilated cardiomyopathy DCM, ischemic cardiomyopathy ICM, atrial fibrillation AF, sinus rhythm/pacemaker lead rhythm SR/PM) were treated with dobutamine or levosimendan. Non-invasive hemodynamics, biomarkers, and parameters of renal organ function were evaluated at hospital admission and after myocardial recompensation (day 5 to 7). RESULTS: Twenty-seven patients with ICM and twenty-three patients with DCM were included. Thirty-nine patients were treated with dobutamine and eleven with levosimendan. Sixteen were accompanied by persistent AF and thirty-four presented either with SR or PM. In the overall cohort, body weight and biomarkers (NT-proBNP/ST2) significantly decreased. GFR significantly increased during therapy with either dobutamine or levosimendan. However, hemodynamic parameters seem to be only improved in patients with DCM, in the levosimendan sub-group, and in patients with SR/PM. CONCLUSION: Patients with acute decompensated HF benefit from positive inotropic therapy during short-term follow-ups. In particular, patients with DCM, those after levosimendan therapy and those with SR/PM, seem to benefit most from inotropic therapy.

Renal Protection and Hemodynamic Improvement by Impella® Microaxial Pump in Patients with Cardiogenic Shock.

Acute kidney injury is one of the most frequent and prognostically relevant complications in cardiogenic shock. The purpose of this study was to evaluate the potential effect of the Impella® pump on hemodynamics and renal organ perfusion in patients with myocardial infarction complicating cardiogenic shock. Between January 2020 and February 2022 patients with infarct-related cardiogenic shock supported with the Impella® pump were included in this single-center prospective short-term study. Changes in hemodynamics on different levels of Impella® support were documented with invasive pulmonal arterial catheter. As far as renal function is concerned, renal perfusion was assessed by determining the renal resistive index (RRI) using Doppler sonography. A total of 50 patients were included in the analysis. The increase in the Impella® output by a mean of 1.0 L/min improved the cardiac index (2.7 ± 0.86 to 3.3 ± 1.1 p < 0.001) and increased central venous oxygen saturation (62.6 ± 11.8% to 67.4 ± 10.5% p < 0.001). On the other side, the systemic vascular resistance (1035 ± 514 N·s/m5 to 902 ± 371 N·s/m5p = 0.012) and the RRI were significantly reduced (0.736 ± 0.07 to 0.62 ± 0.07 p < 0.001). Furthermore, in the overall cohort, a baseline RRI ≥ 0.8 was associated with a higher frequency of renal replacement therapy (71% vs. 39% p = 0.04), whereas the consequent reduction of the RRI below 0.7 during Impella® support improved the glomerular filtration rate (GFR) during hospital stay (15 ± 3 days; 53 ± 16 mL/min to 83 ± 16 mL/min p = 0.04). Impella® support in patients with cardiogenic shock seems to improve hemodynamics and renal organ perfusion. The RRI, a well-known parameter for the early detection of acute kidney injury, can be directly influenced by the Impella® flow rate. Thus, a targeted control of the RRI by the Impella® pump could mediate renal organ protection.

Biventricular Unloading with Impella and Venoarterial Extracorporeal Membrane Oxygenation in Severe Refractory Cardiogenic Shock: Implications from the Combined Use of the Devices and Prognostic Risk Factors of Survival.

Since mechanical circulatory support (MCS) devices have become integral component in the therapy of refractory cardiogenic shock (RCS), we identified 67 patients in biventricular support with Impella and venoarterial Extracorporeal Membrane Oxygenation (VA-ECMO) for RCS between February 2013 and December 2019 and evaluated the risk factors of mortality in this setting. Mean age was 61.07 ± 10.7 and 54 (80.6%) patients were male. Main cause of RCS was acute myocardial infarction (AMI) (74.6%), while 44 (65.7%) were resuscitated prior to admission. The mean Simplified Acute Physiology Score II (SAPS II) and Sequential Organ Failure Assessment Score (SOFA) score on admission was 73.54 ± 16.03 and 12.25 ± 2.71, respectively, corresponding to an expected mortality of higher than 80%. Vasopressor doses and lactate levels were significantly decreased within 72 h on biventricular support (p < 0.05 for both). Overall, 17 (25.4%) patients were discharged to cardiac rehabilitation and 5 patients (7.5%) were bridged successfully to ventricular assist device implantation, leading to a total of 32.8% survival on hospital discharge. The 6-month survival was 31.3%. Lactate > 6 mmol/L, vasoactive score > 100 and pH < 7.26 on initiation of biventricular support, as well as Charlson comorbity index > 3 and prior resuscitation were independent predictors of survival. In conclusion, biventricular support with Impella and VA-ECMO in patients with RCS is feasible and efficient leading to a better survival than predicted through traditional risk scores, mainly via significant hemodynamic improvement and reduction in lactate levels.

Outcomes after transcatheter aortic valve replacement in older patients.

BACKGROUND: The prevalence of aortic valve stenosis is increasing due to the continuously growing geriatric population. Data on procedural success and mortality of very old patients are sparse, raising the question of when this population may be deemed as "too old even for transcatheter aortic valve replacement (TAVR)." We, therefore, sought to evaluate the influence of age on outcome after TAVR and the impact of direct implantation. METHODS: The data of 394 consecutive patients undergoing TF-TAVR were analyzed. Patients were divided into four age groups: ≤75 (group 1, n = 28), 76-80 (group 2, n = 107), 81-85 (group 3, n = 148), and >85 (group 4, n = 111) years. Direct implantation was performed when possible according to current recommendations. Survival was evaluated by Kaplan-Meier analysis. RESULTS: Mortality at 30 days and 1 year was not significantly different between the four age groups (3.6 vs. 6.7 vs. 5.4 vs. 2.7% and 7.6 vs. 17 vs. 14.5 vs. 13%m respectively, log-rank p = 0.59). Direct implantation without balloon aortic valvuloplasty was more frequently performed on patients aged >85 vs. ≤85 years (33.3 vs. 14.1%, p < 0.001). the incidence of procedural complications frequently associated with advanced age (stroke, vascular complications) was not significantly increased in group 4. CONCLUSION: Outcome after TF-TAVR is comparable among different age cohorts, even in very old patients. Direct implantation simplifies the procedure and could therefore play a role in reducing the incidence of peri-interventional complications in patients of advanced age.

Impact of microaxillar mechanical left ventricular support on renal resistive index in patients with cardiogenic shock after myocardial infarction: a pilot trial to predict renal organ dysfunction in cardiogenic shock.

OBJECTIVES: To evaluate the effects of left ventricular support with the microaxial left ventricular pump using the Impella device on the renal resistive index assessed by Doppler ultrasonography in haemodynamically stable patients with cardiogenic shock following myocardial infarction. METHODS: A non-randomised interventional single-centre study. Consecutive patients with cardiogenic shock supported with an Impella were included during May 2018 and October 2018. The renal resistive index determined as a quotient of (peak systolic velocity - end diastolic velocity)/ peak systolic velocity was obtained using Doppler ultrasound; invasive blood pressure was determined in radial artery simultaneously for safety reasons. RESULTS: A total of 15 patients were measured. The renal resistive index was determined in both kidneys in 13 patients and for one kidney in two patients, respectively. The mean difference between right and left renal resistive index was 0.026 ± 0.023 (P=0.72). When increasing the Impella microaxillar mechanical support by a mean of 0.44 L/min (±0.2 L/min), the renal resistive index decreased significantly from 0.66 ± 0.08 to 0.62 ± 0.06 (P<0.001) consistently in all patients, whereas systolic or diastolic blood pressure remained unchanged. CONCLUSIONS: Microaxillar mechanical support by the Impella device in haemodynamically stable patients with cardiogenic shock led to a significant reduction of the renal resistive index without affecting systolic or diastolic blood pressure. This observation is consistent with the notion that Impella support may promote renal organ protection by enhancing renal perfusion.

Clinical impact of TP53 alterations in adrenocortical carcinomas.

BACKGROUND: To evaluate the role of somatic TP53 mutations and to correlate somatic and germline mutations with results of immunostaining, a large cohort of ACC patients was analyzed. PATIENTS AND METHODS: Patients with ACC who underwent potential curative surgery at the authors' department were screened for TP53 somatic and germline mutations in exons 5, 6, 7, 8, and 10 by DHPLC analysis. Aberrant samples were further analyzed by direct sequencing. Immunostaining was performed on corresponding paraffin sections in all patients. Complete clinical and follow-up data were correlated with the status of TP53. RESULTS: Thirty ACC patients were included. Four of 30 patients showed aberrant DHPLC configuration and direct sequencing confirmed 2 (7%) germline mutations (R337H, R248W), 1 (3%) somatic mutation (R213X), and 1 (3%) noncoding polymorphism (g.17708 A>T). The only patient with a positive family history harbored a TP53 mutation. Tumors of the three patients with mutations showed aberrant p53 expression in more than 10% of cells by immunostaining, compared to only 3 of 27 patients without mutations (p = 0.009). Aberrant p53 expression (>5%) was detected in 12/30 (40%) ACCs. The latter was associated with an increased Ki67 and van Slooten index (p ≤ 0.001; p = 0.020). Disease-free survival decreased significantly in patients with aberrant p53 IHC of more than 5% of cells (65.7 ± 12.4 vs. 26.6 ± 8.7 months; p = 0.043 log rank test). CONCLUSIONS: Patients with ACC revealed aberrant expression of p53 in 40%, and mutations were identified in 25% of these patients. Therefore aberrant p53 expression should be considered an indicator for genetic testing. A subgroup of apparently sporadic ACC is caused by TP53 germline mutations, and family history is a strong indicator for p53 germline mutations.