Pioglitazone treatment mitigates cardiovascular bioprosthetic degeneration in a chronic kidney disease model.

Aims: Chronic kidney disease (CKD) is a risk factor for the development of cardiovascular diseases, e.g., atherosclerosis and calcific aortic valve disease, leading inevitably to valve replacement surgery. CKD patients with bioprosthetic cardiovascular grafts, in turn, have a higher risk of premature graft degeneration. Peroxisome proliferator-activated receptor gamma (PPARγ) activation by pioglitazone has cardio-renal protective properties, and research using a heterotopic valve implantation model has shown anti-degenerative effects of PPARγ activation on bioprosthetic valved grafts (BVG) in rats. The present work aims to analyze a potential protective effect of pioglitazone treatment on BVG in an adenine-induced rat model of CKD. Methods and Results: BVG of Sprague Dawley rats were heterotopically implanted in Wistar rats in an infrarenal position for 4 and 8 weeks. Animals were distributed into three groups for each time point: 1) control group receiving standard chow, 2) CKD group receiving 0.25% adenine and 3) CKD + pioglitazone group (300 mg per kg of 0.25% adenine chow). BVG function was analyzed by echocardiography. Plasma analytes were determined and explanted grafts were analyzed by semi-quantitative real-time PCR, Western blot analysis, histology and immunohistology.PPARγ activation significantly reduced CKD-induced calcification of aortic and valvular segments of BVG by 44% and 53%, respectively. Pioglitazone treatment significantly also reduced CKD-induced intima hyperplasia by 60%. Plasma analysis revealed significantly attenuated potassium and phosphate levels after pioglitazone treatment. Moreover, PPARγ activation led to significantly decreased interleukin-6 gene expression (by 57%) in BVG compared to CKD animals. Pioglitazone treatment leads to functional improvement of BVG. Conclusion: This study broadens the understanding of the potential value of PPARγ activation in cardio-renal diseases and delineates pioglitazone treatment as a valuable option to prevent bioprosthetic graft failure in CKD. Further mechanistic studies, e.g., using small molecules activating PPARγ signaling pathways, are necessary for the evaluation of involved mechanisms. Additionally, the translation into pre-clinical studies using large animals is intended as the next research project.

Outcomes following heart valve surgery in patients with infective endocarditis and preoperative septic cerebral embolism: insights from the CAMPAIGN study group.

OBJECTIVES: This study aimed to analyse the impact of preoperative septic cerebral embolism on early and late postoperative outcomes in patients with infective endocarditis undergoing valve surgery. METHODS: Retrospective multicentric study based on the Clinical Multicentric Project for Analysis of Infective Endocarditis in Germany (CAMPAIGN) registry comprising patients with infective endocarditis who underwent valve surgery between 1994 and 2018 at 6 German centres. Patients were divided into 2 groups for statistical comparison according to the presence or absence of preoperative septic cerebral embolism. Propensity score matching was performed for adjusted comparisons of postoperative outcomes. Primary outcomes were 30-day mortality and estimated 5-year survival. RESULTS: A total of 4917 patients were included in the analysis, 3909 (79.5%) patients without and 1008 (20.5%) patients with preoperative septic cerebral embolism. Patients with preoperative septic cerebral embolism had more baseline comorbidities. Mitral valve endocarditis (44.1% vs 33.0% P < 0.001), large vegetations >10 mm (43.1% vs 30.0%, P < 0.001), and Staphylococcus species infection (42.3% vs 21.3%, P < 0.001) were more frequent in the cerebral embolism group. Among patients with preoperative cerebral embolism, 286 (28.4%) patients had no stroke signs (silent stroke). After matching (1008 matched pairs), there was no statistically significant difference in 30-day mortality (20.1% vs 22.8%; P = 0.14) and 5-year survival (47.8% vs 49.1%; stratified log-rank P = 0.77) in patients with and without preoperative cerebral embolism, respectively. CONCLUSIONS: Preoperative septic cerebral embolism in patients with infective endocarditis requiring valve surgery does not negatively affect early or late mortality; therefore, it should not play a major role in deciding if surgery is to be performed.

Severe Vasoplegic Shock After Heart Transplant Successfully Treated With Multimodal Therapeutic Approach.

Vasoplegia describes a constellation of low vascular resistance and normal cardiac output. Vasoplegia is common after cardiac surgery in general and in heart transplant recipients more specifically and occurs in over one-half of all heart transplant recipients with a varying degree of severity. The pathophysiology of vasoplegia is multifactorial and associated with a cascade of inflammatory mediators. Routine treatment of vasoplegia is based on medical vasopressor therapy, but in severe cases this may be insufficient to maintain adequate blood pressure and does not address the underlying pathophysiology. We report a case of severe vasoplegic shock in a heart transplant recipient who was successfully managed with a multimodal therapy combination of methylene blue, immunoglobulins enriched with immunoglobulin M, cytokine adsorption, and broad-spectrum antibiotics. This represents a promising therapeutic approach for heart transplant patients with vasoplegia.

Feasibility, Accuracy, and Reproducibility of Aortic Valve Sizing for Transcatheter Aortic Valve Implantation Using Virtual Reality.

BACKGROUND: Detailed visualization and precise measurements of aortic valve dimensions are critical for the success of transcatheter aortic valve implantation and for the prevention of complications. Currently, multislice computed tomography is the gold standard for assessment of the aortic annulus and surrounding structures to determine the prosthesis size. New technologies such as virtual reality (VR) not only enable 3-dimensional (3D) visualization with the potential to improve understanding of anatomy and pathology but also allow measurements in 3D. This study aims to investigate the feasibility, accuracy, and reproducibility of VR for the visualization of the aortic valve, the surrounding structures, and its role in preprocedural sizing for transcatheter aortic valve implantation. METHODS AND RESULTS: Based on the preprocedural multislice computed tomography data, 3mensio measurements and 3D visualizations and measurements using VR software were performed retrospectively on 60 consecutive patients who underwent transcatheter aortic valve implantation at our heart center. There were no significant differences but strong correlations between the VR measurements compared with those performed with the 3mensio software. Furthermore, excellent or good intra- and interobserver reliability could be demonstrated for all values. In a structured questionnaire, users reported that VR simplified anatomical understanding, improved 3D comprehension of adjacent structures, and was associated with very good self-perceived depth perception. CONCLUSIONS: The use of VR for preprocedural transcatheter aortic valve implantation sizing is feasible and has precise and reproducible measurements. In addition, 3D visualization improves anatomical understanding and orientation. To evaluate the potential benefits of 3D visualization for planning further cardiovascular interventions, research in this field is needed.

Sex-related differences in patients with infective endocarditis requiring cardiac surgery: insights from the CAMPAIGN Study Group.

OBJECTIVES: Sex-related differences play a role in cardiovascular disease-related outcomes. There is, however, a knowledge gap regarding sex-specific differences in patients with infective endocarditis (IE)-requiring surgical treatment. This study aims to analyse sex-related differences in the clinical presentation, treatment and clinical outcomes of patients with IE-requiring surgical treatment from the multicentric Germany-wide CAMPAIGN registry. METHODS: Patients with IE who underwent cardiac surgery between 1994 and 2018 at six German centres were retrospectively analysed. Outcomes were compared based on patients' sex. Primary outcomes were 30-day mortality and mid-term survival. RESULTS: A total of 4917 patients were included in the analysis (1364 female [27.7%] and 3553 male [72.3%]). Female patients presented with more comorbidities and higher surgical risk (EuroScore II 12.0% vs 10.0%, P < 0.001). The early postoperative course of female patients was characterized by longer ventilation times (20.0 h vs 16.0 h; P = 0.004), longer intensive care unit stay (4.0 days vs 3.0 days; P < 0.001), and more frequent new-onset dialysis (265 [20.3%] vs 549 [16.3%]; P = 0.001). The 30-day mortality was 13.8% and 15.5% in female and male patients, respectively (P = 0.06). The estimated mid-term survival was significantly higher amongst male patients (56.1% vs 45.4%; Log-rank P < 0.001). Female sex was an independent predictor of mid-term mortality (HR 1.2 [95% CI 1.0-1.4], P = 0.01). CONCLUSIONS: Male patients more frequently undergo cardiac surgery for IE. However, female patients have a higher surgical risk profile and subsequently an increased early postoperative morbidity, but with similar 30-day mortality compared with male patients. The estimated mid-term survival is lower amongst female patients.

The Predictive Role of Metabolic Volume Segmentation Compared to Semiquantitative PET Parameters in Diagnosis of LVAD Infection using [18F]FDG Imaging.

PURPOSE: Left ventricular assisting device (LVAD) is a vital mechanical circulatory assist device for patients with end-stage heart disease, serving as either a bridge to transplantation or palliative destination therapy. Yet device infection represents a major lethal complication, warranting a multi-step, complex therapy approach including an urgent device exchange or heart transplantation. Still, timely diagnosis of site and extent of VAD-specific infection for a proper therapy planning poses challenges in regular clinical care. This single-center, retrospective study aimed to evaluate the impact of volumetric PET parameters with different thresholding compared to semiquantitative PET parameters for accurate diagnosis of VAD-specific infection. PROCEDURES: Seventeen patients (1 female, 16 males; mean age 57 ± 11 years) underwent [18F]FDG imaging for suspected VAD-specific infection between April 2013 and October 2023. Various metabolic and volumetric PET parameters with different thresholding were collected for specific LVAD components including driveline entry point, subcutaneous driveline, pump pocket, inner cannula and outflow tract. Microbiology and clinical follow-up were used as the final diagnosis standard. RESULTS: Nine of eleven patients with VAD-specific infection underwent urgent heart transplantation, and one had a surgical revision of LVAD. Two patients had non-VAD specific infections, and two had non-VAD related infections. Metabolic burden determination using a fixed absolute threshold provided the best outcome compared to relative thresholding or other metabolic SUV parameters. The total metabolic tumor volume (MTV) cutoff value was 9.3 cm3, and the corresponding sensitivity, specificity, accuracy, and AUC were 90.0%, 71.43%, 82.5%, and 0.814 (95% CI 0.555-0.958), respectively. The total lesion glycolysis (TLG) was 30.6, and the corresponding sensitivity, specificity, accuracy, and AUC were 90.0%, 71.4%, 82.5%, and 0.829 (95% CI 0.571-0.964), respectively. CONCLUSIONS: Volumetric PET parameters with fixed absolute thresholding appear to be a valuable auxiliary tool in the evaluation of [18F]FDG imaging to enhance the diagnostic accuracy of VAD-specific infection.

Five-year results from a prospective, single-arm European trial on decellularized allografts for aortic valve replacement-the ARISE Study and ARISE Registry Data.

OBJECTIVES: Decellularized aortic homografts (DAH) were introduced as a new option for aortic valve replacement for young patients. METHODS: A prospective, EU-funded, single-arm, multicentre study in 8 centres evaluating non-cryopreserved DAH for aortic valve replacement. RESULTS: A total of 144 patients (99 male) were prospectively enrolled in the ARISE Trial between October 2015 and October 2018 with a median age of 30.4 years [interquartile range (IQR) 15.9-55.1]; 45% had undergone previous cardiac operations, with 19% having 2 or more previous procedures. The mean implanted DAH diameter was 22.6 mm (standard deviation 2.4). The median operation duration was 312 min (IQR 234-417), the median cardiopulmonary bypass time was 154 min (IQR 118-212) and the median cross-clamp time 121 min (IQR 93-150). No postoperative bypass grafting or renal replacement therapy were required. Two early deaths occurred, 1 due to a LCA thrombus on day 3 and 1 due ventricular arrhythmia 5 h postoperation. There were 3 late deaths, 1 death due to endocarditis 4 months postoperatively and 2 unrelated deaths after 5 and 7 years due to cancer and Morbus Wegener resulting in a total mortality of 3.47%. After a median follow-up of 5.9 years [IQR 5.1-6.4, mean 5.5 years. (standard deviation 1.3) max. 7.6 years], the primary efficacy end-points peak gradient with median 11.0 mmHg (IQR 7.8-17.6) and regurgitation of median 0.5 (IQR 0-0.5) of grade 0-3 were excellent. At 5 years, freedom from death/reoperation/endocarditis/bleeding/thromboembolism were 97.9%/93.5%/96.4%/99.2%/99.3%, respectively. CONCLUSIONS: The 5-year results of the prospective multicentre ARISE trial continue to show DAH to be safe for aortic valve replacement with excellent haemodynamics.

Pectoral muscle mass is not a robust prognostic factor for survival after left ventricular assist device (LVAD) implantation.

BACKGROUND: Left ventricular assist devices (LVAD) are an established treatment for end-stage left ventricular heart failure. Parameters are needed to identify the most appropriate patients for LVADs. This study aimed to evaluate pectoral muscle mass and density as prognostic parameters. METHODS: This single-center study included all patients with LVAD implantation between January 2010 and October 2017 and a preoperative chest CT scan. Pectoral muscle mass was assessed using the Pectoralis Muscle Index (PMI, surface area indexed to height, cm2/m2) and pectoral muscle density by Hounsfield Units (HU). Overall mortality was analyzed with Kaplan-Meier survival analysis and 1-year and 3-year mortality with receiver operating characteristic (ROC) curves and Cox regression models. RESULTS: 57 patients (89.5% male, mean age 57.8 years) were included. 64.9% of patients had end-stage left ventricular failure due to ischemic heart disease and 35.1% due to dilated cardiomyopathy. 49.2% of patients had preoperative INTERMACS profile of 1 or 2 and 33.3% received mechanical circulatory support prior to LVAD implantation. Total mean PMI was 4.7 cm2/m2 (± 1.6), overall HU of the major pectoral muscle was 39.0 (± 14.9) and of the minor pectoral muscle 37.1 (± 16.6). Mean follow-up was 2.8 years (± 0.2). Mortality rates were 37.5% at 1 year and 48.0% at 3 years. Neither PMI nor HU were significantly associated with overall mortality at 1-year or 3-year. CONCLUSIONS: The results of our study do not confirm the association between higher pectoral muscle mass and better survival after LVAD implantation previously described in the literature.

Association between early postoperative hypoalbuminaemia and outcome after orthotopic heart transplantation.

OBJECTIVES: In patients undergoing heart transplantation (HTX), preoperative liver impairment and consecutive hypoalbuminaemia are associated with increased mortality. The role of early postoperative hypoalbuminaemia after HTX is unclear. This study investigated the association between early postoperative hypoalbuminaemia and 1-year mortality as well as 'days alive and out of hospital' (DAOH) after HTX. METHODS: This retrospective cohort study included patients who underwent HTX at the University Hospital Duesseldorf, Germany, between 2010 and 2022. The main exposure was serum albumin concentration at intensive care unit (ICU) arrival. The primary endpoints were mortality and DAOH within 1 year after surgery. Receiver operating characteristic (ROC) curve analysis was performed and logistic and quantile regression models with adjustment for 13 a priori defined clinical risk factors were conducted. RESULTS: Out of 241 patients screened, 229 were included in the analysis (mean age 55 ± 11 years, 73% male). ROC analysis showed moderate discrimination for 1-year mortality by postoperative serum albumin after HTX [AUC = 0.74; 95% confidence interval (CI): 0.66-0.83]. The cutoff for serum albumin at ICU arrival was 3.0 g/dl. According to multivariate logistic and quantile regression, there were independent associations between hypoalbuminaemia and mortality/DAOH [odds ratio of 4.76 (95% CI: 1.94-11.67) and regression coefficient of -46.97 (95% CI: -83.81 to -10.13)]. CONCLUSIONS: Postoperative hypoalbuminaemia <3.0 g/dl is associated with 1-year mortality and reduced DAOH after HTX and therefore might be used for early postoperative risk re-assessment in clinical practice.

A successful cardiac transplant in a patient with situs inversus totalis and congenitally corrected transposition of the great arteries.

A heart transplant is the gold standard therapy for patients with end-stage heart failure. In this case report, situs inversus totalis and congenitally corrected transposition of the great arteries led to a unique and complex preoperative setting. Extended donor organ harvesting, donor graft rotation of 45° to the right and post-operative stenting of the superior vena cava were essential steps in the interdisciplinary management of this case. The patient was transferred to the intensive care unit with moderate inotropic support. He was discharged to rehabilitation on postoperative day 89 and eventually underwent an additional renal transplant 14 months after the cardiac transplant.

Treatment of Refractory Cardiac Arrest by Controlled Reperfusion of the Whole Body: A Multicenter, Prospective Observational Study.

Background: Survival following cardiac arrest (CA) remains poor after conventional cardiopulmonary resuscitation (CCPR) (6-26%), and the outcomes after extracorporeal cardiopulmonary resuscitation (ECPR) are often inconsistent. Poor survival is a consequence of CA, low-flow states during CCPR, multi-organ injury, insufficient monitoring, and delayed treatment of the causative condition. We developed a new strategy to address these issues. Methods: This all-comers, multicenter, prospective observational study (69 patients with in- and out-of-hospital CA (IHCA and OHCA) after prolonged refractory CCPR) focused on extracorporeal cardiopulmonary support, comprehensive monitoring, multi-organ repair, and the potential for out-of-hospital cannulation and treatment. Result: The overall survival rate at hospital discharge was 42.0%, and a favorable neurological outcome (CPC 1+2) at 90 days was achieved for 79.3% of survivors (CPC 1+2 survival 33%). IHCA survival was very favorable (51.7%), as was CPC 1+2 survival at 90 days (41%). Survival of OHCA patients was 35% and CPC 1+2 survival at 90 days was 28%. The subgroup of OHCA patients with pre-hospital cannulation showed a superior survival rate of 57.1%. Conclusions: This new strategy focusing on repairing damage to multiple organs appears to improve outcomes after CA, and these findings should provide a sound basis for further research in this area.