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Background Vasoplegic syndrome is frequently observed during cardiac surgery and resembles a complication of high mortality and morbidity. There is a clinical need for therapy and prevention of vasoplegic syndrome during complex cardiac surgical procedures. Therefore, we investigated different strategies in a porcine model of vasoplegia.
Methods We evaluated new medical therapies and prophylaxis to avoid vasoplegic syndrome in a porcine model. After induction of anesthesia, cardiopulmonary bypass was established through median sternotomy and central cannulation. Prolonged aortic cross-clamping (120 min) simulated a complex surgical procedure. The influence of sevoflurane-guided anesthesia (sevoflurane group) and the administration of glibenclamide (glibenclamide group) were compared to a control group, which received standard anesthesia using propofol. Online hemodynamic assessment was performed using PiCCO® measurements. In addition, blood and tissue samples were taken to evaluate hemodynamic effects and the degree of inflammatory response.
Results Glibenclamide was able to break through early vasoplegic syndrome by raising the blood pressure and systemic vascular resistance as well as less need of norepinephrine doses. Sevoflurane reduced the occurrence of the vasoplegic syndrome in the mean of stable blood pressure and less need of norepinephrine doses.
Conclusion Glibenclamide could serve as a potent drug to reduce effects of vasoplegic syndrome. Sevoflurane anesthesia during cardiopulmonary bypass shows less occurrence of vasoplegic syndrome and therefore could be used to prevent it in high-risk patients.
Clinical Perspective; what is new?
* to our knowledge, this is the first randomized in vivo study evaluating the hemodynamic effects of glibenclamide after the onset of vasoplegic syndrome
* furthermore according to literature research, there is no study showing the effect of sevoflurane-guided anesthesia on the occurrence of a vasoplegic syndrome
Clinical Perspective; clinical implications?
to achieve better outcomes after complex cardiac surgery there is a need for optimized drug therapy and prevention of the vasoplegic syndrome
Improved integration of single cell transcriptome data demonstrated on heart failure in mice and men
(2023)
Biomedical research frequently uses murine models to study disease mechanisms. However, the translation of these findings to human disease remains a significant challenge. In order to improve the comparability of mouse and human data, we present a cross-species integration pipeline for single-cell transcriptomic assays.
The pipeline merges expression matrices and assigns clear orthologous relationships. Starting from Ensembl ortholog assignments, we allocated 82% of mouse genes to unique orthologs by using additional publicly available resources such as Uniprot, and NCBI databases. For genes with multiple matches, we employed the Needleman-Wunsch global alignment based on either amino acid or nucleotide sequence to identify the ortholog with the highest degree of similarity.
The workflow was tested for its functionality and efficiency by integrating scRNA-seq datasets from heart failure patients with the corresponding mouse model. We were able to assign unique human orthologs to up to 80% of the mouse genes, utilizing the known 17,492 orthologous pairs. Curiously, the integration process enabled the identification of both common and unique regulatory pathways between species in heart failure.
In conclusion, our pipeline streamlines the integration process, enhances gene nomenclature alignment and simplifies the translation of mouse models to human disease. We have made the OrthoIntegrate R-package accessible on GitHub (https://github.com/MarianoRuzJurado/OrthoIntegrate), which includes the assignment of ortholog definitions for human and mouse, as well as the pipeline for integrating single cells.
Background: Cerebral oxygen saturation (ScO2) can be measured non-invasively by near-infrared spectroscopy (NIRS) and correlates with cerebral perfusion. We investigated cerebral saturation during transfemoral transcatheter aortic valve implantation (TAVI) and its impact on outcome.
Methods and results: Cerebral oxygenation was measured continuously by NIRS in 173 analgo-sedated patients during transfemoral TAVI (female 47%, mean age 81 years) with self-expanding (39%) and balloon-expanding valves (61%). We investigated the periprocedural dynamics of cerebral oxygenation. Mean ScO2 at baseline without oxygen supply was 60%. During rapid ventricular pacing, ScO2 dropped significantly (before 64% vs. after 55%, p < 0.001). ScO2 at baseline correlated positively with baseline left-ventricular ejection fraction (0.230, p < 0.006) and hemoglobin (0.327, p < 0.001), and inversely with EuroSCORE-II ( − 0.285, p < 0.001) and length of in-hospital stay ( − 0.229, p < 0.01). Patients with ScO2 < 56% despite oxygen supply at baseline had impaired 1 year survival (log-rank test p < 0.01) and prolonged in-hospital stay (p = 0.03). Furthermore, baseline ScO2 was found to be a predictor for 1 year survival independent of age and sex (multivariable adjusted Cox regression, p = 0.020, hazard ratio (HR 0.94, 95% CI 0.90–0.99) and independent of overall perioperative risk estimated by EuroSCORE-II and hemoglobin (p = 0.03, HR 0.95, 95% CI 0.91–0.99).
Conclusions: Low baseline ScO2 not responding to oxygen supply might act as a surrogate for impaired cardiopulmonary function and is associated with worse 1 year survival and prolonged in-hospital stay after transfemoral TAVI. ScO2 monitoring is an easy to implement diagnostic tool to screen patients at risk with a potential preserved recovery and worse outcome after TAVI.
Background: The aim of this study was to identify pre-operative parameters able to predict length of stay (LoS) based on clinical data and patient-reported outcome measures (PROMs) from a scorecard database in patients with significant aortic stenosis who underwent TAVI (transfemoral aortic valve implantation). Methods: 302 participants (51.7% males, age range 78.2–84.2 years.) were prospectively recruited. After computing the median LoS value (=6 days, range = 5–8 days), we implemented a decision tree algorithm by setting dichotomized values at median LoS as the dependent variable and assessed baseline clinical variables and PROMs (Clinical Frailty Scale (CFS), EuroQol-5 Dimension-5 Levels (EQ-5D) and Kansas City Cardiomyopathy Questionnaire (KCCQ)) as potential predictors. Results: Among clinical parameters, only peripheral arterial disease (p = 0.029, HR = 1.826) and glomerular filtration rate (GFR, cut-off < 33 mL/min/1.73 m2, p = 0.003, HR = 2.252) were predictive of LoS. Additionally, two PROMs (CFS; cut-off = 3, p < 0.001, HR = 1.324 and KCCQ; cut-off = 30, p = 0.003, HR = 2.274) were strong predictors. Further, a risk score for LoS (RS_LoS) was calculated based on these predictors. Patients with RS_LoS = 0 had a median LoS of 5 days; patients RS_LoS ≥ 3 had a median LoS of 8 days. Conclusions: based on the pre-operative values of the above four predictors, a personalized prediction of LoS after TAVI can be achieved.
We present the case of an adult male patient with an incomplete form of Shone’s complex associated with bicuspid aortic valve and a double orifice mitral valve. Intraoperative inspection of the mitral valve showed double orifice configuration with a small, rudimentary left-sided mitral valve and a large, dominant, right-sided parachute mitral valve with Barlow-type of degeneration. The patient underwent reconstruction of both valves through a minimally invasive incision. At one year echocardiographic control both valves function normally.
Background: The aim of this study was to evaluate the longer-term results of bicuspid aortic valve (BAV) repair with or without aortic root replacement. Methods: From 1999 to 2017, 142 patients with or without aortic root dilatation who underwent repair of a regurgitant BAV were included in the study. Ninety-four patients underwent isolated BAV repair (Group 1; median age 43 years) and 48 patients underwent valve-sparing aortic root replacement plus BAV repair (aortic valve reimplantation—Group 2; median age 48 years). Median clinical follow-up time was 5.9 years (range 0.5–15) in Group 1 and 3 years (range 0.5–16) in Group 2, respectively. Results: In-hospital mortality was 1% in Group 1, and 2% in Group 2 (p = .6). The 5- and 10-year survival was 93 ± 2.9% and 81 ± 5.8% in Group 1 and 96 ± 3.1% and 96 ± 3.1% in Group 2, respectively (p = .31). Eleven patients of Group 1 (1.7%/patient-year) and five patients of Group 2 (2.2%/patient-year) underwent reoperation of the aortic valve (p = .5). The 5- and 10-year freedom from reoperation were 93.0 ± 2.1% and 77.1 ± 7.1% in Group 1 and 93.0 ± 5.0% and 76.7 ± 9.6% in Group 2 (p = .83), respectively. At the latest follow-up, only two patients of Group 1 and 1 patient of Group 2 had AV regurgitation = 2° (p = .7). The cumulative linearized incidence of all valve-related complications (bleeding, stroke, endocarditis, and reoperation) was 2.9%/patient-year in Group 1% and 4%/patient-year in Group 2, respectively (p = .6). Conclusions: Isolated BAV repair and combined aortic valve reimplantation plus BAV repair provide good clinical longer-term outcomes with relatively low reoperation rate and durable valve function.
Non-standard errors
(2021)
In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in sample estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: non-standard errors. To study them, we let 164 teams test six hypotheses on the same sample. We find that non-standard errors are sizeable, on par with standard errors. Their size (i) co-varies only weakly with team merits, reproducibility, or peer rating, (ii) declines significantly after peer-feedback, and (iii) is underestimated by participants.
Background: Rates of permanent pacemaker implantation (PPI) have been low using the self‐expanding ACURATE neo device, but data regarding risk factors of PPI for this specific device are scarce.
Methods: The study cohort consisted of patients (n = 1000) with severe aortic stenosis undergoing transfemoral transcatheter aortic valve implantation (TAVI) using the ACURATE neo prosthesis in our center between May 2012 and December 2019. For the present analysis, we excluded patients with previous permanent pacemaker (n = 110), high‐grade AV block prior to TAVI (n = 3), and patients requiring conversion to surgical valve replacement (n = 4) or the implantation of a second prosthesis as valve‐in‐valve (n = 15). Preexisting conduction abnormalities were determined, and the implantation depth of the prosthesis was measured on final angiography. Differences across quartiles based on the original consecutive cohort were analyzed with respect to implantation depth and PPI rate. Predictors of PPI were identified using logistic regression.
Results: The PPI rate was 10%. Preexisting AV block I°, right bundle branch block (RBBB), and the implantation depth were independent predictors of PPI. Across quartiles, the implantation depth differed significantly with lowest values in the last quartile, whereas differences of PPI rates across quartiles were not statistically significant, but showed a notable decrease in the last quartile.
Conclusion: Preexisting RBBB, AV block I°, and low implantation depth were independent predictors of PPI following TAVI using the ACURATE neo device. Instead of deliberately aiming at a high position, avoidance of a low implantation depth may represent a reasonable compromise to reduce the rate of PPI without increasing the risk of malpositioning.
Background: Point of care devices for performing targeted coagulation substitution in patients who are bleeding have become increasingly important in recent years. New on the market is the Quantra. It is a device that uses sonorheometry, a sonic estimation of elasticity via resonance, which is a novel ultrasound-based technology that measures viscoelastic properties of whole blood. Several studies have already shown the comparability of the Quantra with devices already established on the market, such as the rotational thromboelastometry (ROTEM) device.
Objective: In contrast to existing studies, this study is the first prospective interventional study using this new system in a cardiac surgical patient cohort. We will investigate the noninferiority between an already existing coagulation algorithm based on the ROTEM/Multiplate system and a new algorithm based on the Quantra system for the treatment of coagulopathic cardiac surgical patients.
Methods: The study is divided into two phases. In an initial observation phase, whole blood samples of 20 patients obtained at three defined time points (prior to surgery, after completion of cardiopulmonary bypass, and on arrival in the intensive care unit) will be analyzed using both the ROTEM/Multiplate and Quantra systems. The obtained threshold values will be used to develop a novel algorithm for hemotherapy. In a second intervention phase, the new algorithm will be tested for noninferiority against an algorithm used routinely for years in our department.
Results: The main objective of the examination is the cumulative loss of blood within 24 hours after surgery. Statistical calculations based on the literature and in-house data suggest that the new algorithm is not inferior if the difference in cumulative blood loss is <150 mL/24 hours.
Conclusions: Because of the comparability of the Quantra sonorheometry system with the ROTEM measurement methods, the existing hemotherapy treatment algorithm can be adapted to the Quantra device with proof of noninferiority.
Trial Registration: ClinicalTrials.gov NCT03902275; https://clinicaltrials.gov/ct2/show/NCT03902275
International Registered Report Identifier (IRRID): DERR1-10.2196/17206
Background: Cerebral O2 saturation (ScO2) reflects cerebral perfusion and can be measured noninvasively by near-infrared spectroscopy (NIRS). Objectives: In this pilot study, we describe the dynamics of ScO2 during TAVI in nonventilated patients and its impact on procedural outcome. Methods and Results: We measured ScO2 of both frontal lobes continuously by NIRS in 50 consecutive analgo-sedated patients undergoing transfemoral TAVI (female 58%, mean age 80.8 years). Compared to baseline ScO2 dropped significantly during RVP (59.3% vs. 53.9%, p < .01). Five minutes after RVP ScO2 values normalized (post RVP 62.6% vs. 53.9% during RVP, p < .01; pre 61.6% vs. post RVP 62.6%, p = .53). Patients with an intraprocedural pathological ScO2 decline of >20% (n = 13) had higher EuroSCORE II (3.42% vs. 5.7%, p = .020) and experienced more often delirium (24% vs. 62%, p = .015) and stroke (0% vs. 23%, p < .01) after TAVI. Multivariable logistic regression revealed higher age and large ScO2 drops as independent risk factors for delirium. Conclusions: During RVP ScO2 significantly declined compared to baseline. A ScO2 decline of >20% is associated with a higher incidence of delirium and stroke and a valid cut-off value to screen for these complications. NIRS measurement during TAVI procedure may be an easy to implement diagnostic tool to detect patients at high risks for cerebrovascular complications and delirium.