Effect of routine preoperative screening for aortic calcifications using noncontrast computed tomography on stroke rate in cardiac surgery: the randomized controlled CRICKET study.

OBJECTIVES: To evaluate if routine screening for aortic calcification using unenhanced CT lowers the risk of stroke and alters the surgical approach in patients undergoing general cardiac surgery compared with standard of care (SoC). METHODS: In this prospective, multicenter, randomized controlled trial, adult patients scheduled for cardiac surgery from September 2014 to October 2019 were randomized 1:1 into two groups: SoC alone, including chest radiography, vs. SoC plus preoperative noncontrast CT. The primary endpoint was in-hospital perioperative stroke. Secondary endpoints were preoperative change of the surgical approach, in-hospital mortality, and postoperative delirium. The trial was halted halfway for expected futility, as the conditional power analysis showed a chance < 1% of finding the hypothesized effect. RESULTS: A total of 862 patients were evaluated (SoC-group: 433 patients (66 ± 11 years; 74.1% male) vs. SoC + CT-group: 429 patients (66 ± 10 years; 69.9% male)). The perioperative stroke rate (SoC + CT: 2.1%, 9/429 vs. SoC: 1.2%, 5/433, p = 0.27) and rate of changed surgical approach (SoC + CT: 4.0% (17/429) vs. SoC: 2.8% (12/433, p = 0.35) did not differ between groups. In-hospital mortality and postoperative delirium were comparable between groups. In the SoC + CT group, aortic calcification was observed on CT in the ascending aorta in 28% (108/380) and in the aortic arch in 70% (265/379). CONCLUSIONS: Preoperative noncontrast CT in cardiac surgery candidates did not influence the surgical approach nor the incidence of perioperative stroke compared with standard of care. Aortic calcification is a frequent finding on the CT scan in these patients but results in major surgical alterations to prevent stroke in only few patients. KEY POINTS: • Aortic calcification is a frequent finding on noncontrast computed tomography prior to cardiac surgery. • Routine use of noncontrast computed tomography does not often lead to a change of the surgical approach, when compared to standard of care. • No effect was observed on perioperative stroke after cardiac surgery when using routine noncontrast computed tomography screening on top of standard of care.

Alternatives for Vitamin K Antagonists as Thromboprophylaxis for Mechanical Heart Valves and Mechanical Circulatory Support Devices: A Systematic Review.

The holy grail of anticoagulation in patients with intracardiac devices, such as mechanical heart valves (MHVs) and left ventricular assist devices (LVADs), comprises safe prevention of thrombosis without interrupting normal hemostasis. Device-induced thrombosis and anticoagulant-related bleeding problems are dreaded complications that may cause a significantly reduced quality of life and increased morbidity and mortality. Vitamin K antagonists are the current standard for oral anticoagulation therapy in patients with MHVs and LVADs. Even within the therapeutic range, hemorrhage is the primary complication of these drugs, which emphasizes the need for safer anticoagulants for the prevention of device-induced thrombosis. Device-induced thrombosis is a complex multifactorial phenomenon that likely requires anticoagulant therapy targeting multiple pathways. Here, we review the preclinical and clinical data describing the efficacy of a variety of anticoagulants as thromboprophylaxis after implantation of intracardiac devices.

Hallucinations after Cardiac Surgery: A Prospective Observational Study.

Background and Objective: Hallucinations after cardiac surgery can be a burden, but their prevalence and phenomenology have not been studied well. Risk factors for postoperative hallucinations, as well as their relation to delirium are unclear. We aimed to study the prevalence and phenomenology of hallucinations after cardiac surgery, and to study the association between hallucinations and delirium in this population. Materials and Methods: We used the Questionnaire for Psychotic Experiences to detect hallucinations in cardiac surgery patients and a control group of cardiology outpatients. We assessed postoperative delirium with validated instruments. Risk factors for postoperative hallucinations and the association between hallucinations and delirium were analysed using logistic regression. Results: We included 201 cardiac surgery patients and 99 cardiology outpatient controls. Forty-four cardiac surgery patients (21.9%) experienced postoperative hallucinations in the first four postoperative days. This was significantly higher compared to cardiology outpatient controls (n = 4, 4.1%, p < 0.001). Visual hallucinations were the most common type of hallucinations in cardiac surgery patients, and less common in outpatient controls. Cardiac surgery patients who experienced hallucinations were more likely to also have delirium (10/44, 22.7%) compared to patients without postoperative hallucinations (16/157, 10.2% p = 0.03). However, the majority of patients with postoperative hallucinations (34/44, 77.3%) did not develop delirium. Conclusion: After cardiac surgery, hallucinations occurred more frequently than in outpatient controls. Hallucinations after cardiac surgery were most often visual in character. Although postoperative hallucinations were associated with delirium, most patients with hallucinations did not develop delirium.

Determinants of the postpericardiotomy syndrome: a systematic review.

BACKGROUND: Postpericardiotomy syndrome (PPS) is a common complication following cardiac surgery; however, the exact pathogenesis remains uncertain. Identifying risk factors of PPS might help to better understand the syndrome. The aim of this study was to provide an overview of existing literature around determinants of PPS in adult cardiac surgery patients. MATERIAL AND METHODS: Two independent investigators performed a systematic search in MEDLINE, EMBASE and the Cochrane Central Register. The search aimed to identify studies published between January 1950 and December 2015, in which determinants of PPS were reported. RESULTS: A total of 19 studies met the selection criteria. In these studies, 14 different definitions of PPS were used. The median incidence of PPS was 16%. After quality assessment, seven studies were considered eligible for this review. Lower preoperative interleukin-8 levels and higher postoperative complement conversion products were associated with a higher risk of PPS. Among other clinical factors, a lower age, transfusion of red blood cells and lower preoperative platelet and haemoglobin levels were associated with a higher risk of PPS. Colchicine use decreased the risk of PPS. CONCLUSION: We found that both the inflammatory response and perioperative bleeding and coagulation may play a role in the development of PPS, suggesting a multifactorial aetiology of the syndrome. Due to a lack of a uniform definition of PPS in the past, study comparability was poor across the studies.

Medium and long-term patency results of distal anastomosis connectors: a meta-analysis.

Background: The difficulty of suturing perfect anastomoses in limited-access conditions prevents the transition of traditional coronary artery bypass grafting (CABG) to sternal-sparing approaches, even in the robotic era. Automated coronary anastomotic connector technologies may address these difficulties, but to date, none have achieved broad adoption. Besides versatility, ease-of-use and cost-effectiveness, the key performance parameter of such technology is anastomotic patency. In this meta-analysis, we aim to evaluate published connector devices by examining their patency outcomes in distal anastomoses. Methods: The literature was systematically searched for studies comparing the angiographic patency of connector constructed coronary anastomoses to handsewn (HS) connections in adult patients undergoing CABG. The primary outcome was anastomosis patency across early (<30 days), mid-term (30 days to 1 year) and long-term (>1 year) follow-up. Random-effects meta-analyses were employed to analyze and compare patency using pooled risk ratios (RR) with 95% confidence intervals (CI). Results: The search yielded 14 studies concerning eight connector devices. In 4,311 patients, a total of 4,328 anastomoses were constructed, 674 with connector devices and 3,654 with a HS technique. The pooled device patency over all timeframes was non-inferior to the HS technique (RR 0.90, 95% CI: 0.56-1.44). Technologies having a relatively large blood-exposed non-intimal surface area (BENIS, >15 mm2) performed acceptably when applied to large target vessels [>2.0-2.5 mm inner diameter (ID)]. A tiny anastomotic orifice area (AOA, < ca. 4 mm2) appeared to adversely affect results. Technologies realizing a generous AOA in combination with a limited BENIS showed superior results and applicability by performing well across the entire range of target coronary artery diameters (>1.0-1.5 mm ID). Conclusions: The overall results suggest that connectors yield at least non-inferior anastomosis patency outcomes compared to HS techniques in all observed timeframes. Optimizing device characteristics like BENIS and AOA appear fundamental for broad applicability.

Cost Analysis of Robot-Assisted Versus On-Pump and Off-Pump Coronary Artery Bypass Grafting: A Single-Center Surgical and 30-Day Outcomes Comparison.

OBJECTIVE: Throughout Europe, the interest in implementing robot-assisted minimally invasive direct coronary artery bypass (RA-MIDCAB) has been growing. However, concerns about additional costs have emerged concurrently. In this analysis, we aim to provide a comparison of the cumulative perioperative costs of RA-MIDCAB, on-pump coronary artery bypass grafting (CABG), and off-pump CABG (OPCAB). METHODS: We conducted a propensity score-matched analysis comparing patients undergoing RA-MIDCAB with those undergoing CABG or OPCAB at our institution from January 2016 to December 2021. After matching, we analyzed the combined intraoperative surgical costs and 30-day postoperative costs. We first compared RA-MIDCAB costs to CABG and then to OPCAB separately. Violin plots illustrated the cost distribution among individual patients. Total cost uncertainty was estimated using 1,000 bootstrapping iterations. RESULTS: Seventy-nine RA-MIDCAB patients were matched to 158 CABG patients, and 80 RA-MIDCAB patients were matched to 149 OPCAB patients. Considering both surgical and clinical outcomes, RA-MIDCAB yielded an average cost of €17,121 per patient (€16,781 to €33,294), CABG was €16,571 per patient (€16,664 to €41,860), and OPCAB was €15,463 per patient (€10,895 to €57,867). After bootstrap iterations, RA-MIDCAB was found to be €472 (2.8%) and €1,599 (10.3%) more expensive per patient than CABG and OPCAB, respectively. CONCLUSIONS: In The Netherlands, the adoption of RA-MIDCAB did not show a significant economic impact on hospital resources. The additional robotic costs for the surgery were almost entirely offset by the cost savings during the postoperative hospital stay. However, these comparisons may differ when considering hybrid coronary revascularization with its additional percutaneous coronary intervention costs.

Diagnostic Accuracy of an Algorithm for Discriminating Presumed Solid and Gaseous Microembolic Signals During Transcranial Doppler Examinations.

OBJECTIVE: The aim of the work described here was to assess the diagnostic accuracy of a new algorithm (SGA-a) for time-domain analysis of transcranial Doppler audio signals to discriminate presumed solid and gaseous microembolic signals and artifacts (SGAs). METHODS: SGA-a was validated by human experts in an artifact cohort of 20 patients subjected to a 1-h transcranial Doppler exam before cardiac surgery (cohort 1). Emboli were validated in a cohort of 10 patients after aortic valve replacement in a 4-h monitoring period (cohort 2). The SGA misclassification rate was estimated by testing SGA-a on artifact-free test files of solid and gaseous emboli. RESULTS: In cohort 1 (n = 24,429), artifacts were classified with an accuracy of 94.5%. In cohort 2 (n = 12,328), the accuracy in discriminating solid/gaseous emboli from artifacts was 85.6%. The 95% limits of agreement for, respectively, the numbers of presumed solids and gaseous emboli, artifacts and microembolic signals of undetermined origin were [-10, 10], [-14, 7] and [-9, 16], and the intra-class correction coefficients were 0.99, 0.99 and 0.99, respectively. The rate of misclassification of solid test files was 2%, and the rate of misclassification of gaseous test files was 12%. CONCLUSION: SGA-a can detect presumed solid and gaseous microembolic signals and differentiate them from artifacts. SGA-a could be of value when both solid and gaseous emboli may jeopardize brain function such as seen during cardiac valve and/or aortic arch replacement procedures.

A Nationwide Study of Clinical Outcomes After Robot-Assisted Coronary Artery Bypass Surgery and Hybrid Revascularization in the Netherlands.

OBJECTIVE: Robot-assisted minimally invasive direct coronary artery bypass (RA-MIDCAB) surgery and hybrid coronary revascularization (HCR) are minimally invasive alternative strategies to conventional coronary artery bypass surgery in patients with isolated left anterior descending (LAD) stenosis or multivessel coronary disease. We analyzed a large, multicenter data-set based on the Netherlands Heart Registration including all patients undergoing RA-MIDCAB. METHODS: We included 440 consecutive patients who underwent RA-MIDCAB with the left internal thoracic artery to LAD between January 2016 and December 2020. A proportion of patients underwent percutaneous coronary intervention (PCI) of non-LAD vessels (i.e., HCR). The primary outcome was all-cause mortality at median follow-up of 1 year, which was subdivided into cardiac and noncardiac. Secondary outcomes included target vessel revascularization (TVR) at median follow-up as well as 30-day mortality, perioperative myocardial infarction, reoperation for bleeding or anastomosis-related problems, and in-hospital ischemic cerebrovascular accident (iCVA). RESULTS: Among all patients, 91 (21%) underwent HCR. At median (IQR) follow-up of 19 (8 to 28) months, 11 patients (2.5%) had died. In 7 patients, the cause of death was defined as cardiac. TVR occurred in 25 patients (5.7%), of whom 4 underwent CABG and 21 underwent PCI. At 30-day follow-up, 6 patients (1.4%) had a perioperative myocardial infarction, of whom 1 died. One patient (0.2%) developed an iCVA, and 18 patients (4.1%) underwent reoperation for bleeding or anastomosis-related problems. CONCLUSIONS: The clinical outcomes of patients undergoing RA-MIDCAB or HCR in the Netherlands are good and promising when compared with the currently available literature.

Acquired blood platelet disorder in patients with end-stage heart failure after implantation of a continuous centrifugal-flow left ventricular assist device: A prospective cohort study.

Background: Continuous-flow left ventricular assist devices (CF-LVADs) are an established therapy for advanced heart failure. Thrombosis and hemorrhage are common complications after CF-LVAD implantation, which may be explained by device-induced platelet activation. Few data on the effect of CF-LVAD implantation on platelets are available to date. Objectives: The aim of this study was to characterize the change in the platelet activation status after CF-LVAD. Methods: Platelet phenotype and reactivity were determined with flow cytometry in 32 adults with end-stage heart failure before and 4 to 6 weeks after CF-LVAD implantation. Sixteen adults with a biological aortic valve prosthesis (AVP) using the same antiplatelet regimen were included to discriminate between the effects of CF-LVAD and the antiplatelet regimen. Plasma markers for platelet activation were determined with enzyme-linked immunosorbent assay. Results: Median (IQR) plasma levels of soluble P-selectin increased from 115.6 (79.1-142.7) ng/mL to 144.5 (100.4-197.5) ng/mL after CF-LVAD implantation (P < .001). Median (IQR) ß-thromboglobulin levels were 60.5 (37.8-81.5) ng/mL before implantation and remained high after LVAD implantation [60.0 (42.0-69.5) ng/mL]. The platelet P-selectin expression after stimulation with ADP (30 and 60 µM) or PAR1-activating peptide (12.5 and 25 µM) was reduced by 17% to 21%, and fibrinogen binding was reduced by 37% to 86%. Platelet responses to agonists were similar in patients with a CF-LVAD and patients with an AVP, except for fibrinogen binding in response to 12.5 µM PAR1-AP, which was lower in patients with a CF-LVAD (P < .001). Conclusions: Combined, these data provide evidence for systemic platelet activation and an acquired platelet disorder after CF-LVAD implantation. This might contribute to the risk of both hemorrhage and thrombosis associated with CF-LVADs.

Cyclic strain has antifibrotic effects on the human cardiac fibroblast transcriptome in a human cardiac fibrosis-on-a-chip platform.

In cardiac fibrosis, in response to stress or injury, cardiac fibroblasts deposit excessive amounts of collagens which contribute to the development of heart failure. The biochemical stimuli in this process have been extensively studied, but the influence of cyclic deformation on the fibrogenic behavior of cardiac fibroblasts in the ever-beating heart is not fully understood. In fact, most investigated mechanotransduction pathways in cardiac fibroblasts seem to ultimately have profibrotic effects, which leaves an important question in cardiac fibrosis research unanswered: how do cardiac fibroblasts stay quiescent in the ever-beating human heart? In this study, we developed a human cardiac fibrosis-on-a-chip platform and utilized it to investigate if and how cyclic strain affects fibrogenic signaling. The pneumatically actuated platform can expose engineered tissues to controlled strain magnitudes of 0-25% - which covers the entire physiological and pathological strain range in the human heart - and to biochemical stimuli and enables high-throughput screening of multiple samples. Microtissues of human fetal cardiac fibroblasts (hfCF) embedded in gelatin methacryloyl (GelMA) were 3D-cultured on this platform and exposed to strain conditions which mimic the healthy human heart. The results provide evidence of an antifibrotic effect of the applied strain conditions on cardiac fibroblast behavior, emphasizing the influence of biomechanical stimuli on the fibrogenic process and giving a detailed overview of the mechanosensitive pathways and genes involved, which can be used in the development of novel therapies against cardiac fibrosis.

MarioHeart: Novel In-Vitro Flow Model for Testing Heart Valve Prostheses and Anticoagulant Therapies.

Mechanical heart valve (MHV) prostheses present a risk of thromboembolic complications despite antithrombotic therapy. Further steps in the development of more hemocompatible MHVs and new anticoagulants are impeded due to the lack of adequate in-vitro models. With the development of a novel in-vitro model (MarioHeart), a pulsatile flow similar to the arterial circulation is emulated. The MarioHeart design owns unique features as 1) a single MHV within a torus with low surface/volume ratio, 2) a closed loop system, and 3) a dedicated external control system driving the oscillating rotational motion of the torus. For verification purposes, a blood analog fluid seeded with particles was used to assess fluid velocity and flow rate using a speckle tracking method on high-speed video recordings of the rotating model. The flow rate resembled the physiological flow rate in the aortic root, in both shape and amplitude. Additional in-vitro runs with porcine blood showed thrombi on the MHV associated with the suture ring, which is similar to the in-vivo situation. MarioHeart is a simple design which induces well-defined fluid dynamics resulting in physiologically nonturbulent flow without stasis of the blood. MarioHeart seems suitable for testing the thrombogenicity of MHVs and the potential of new anticoagulants.

Insights in the Prothrombotic Changes After Implantation of a Left Ventricular Assist Device in Patients With End-Stage Heart Failure: A Longitudinal Observational Study.

Thrombus formation is a common complication during left ventricular assist device (LVAD) therapy, despite anticoagulation with vitamin K antagonists (VKA) and a platelet inhibitor. Plasma levels of markers for primary and secondary hemostasis and contact activation were determined before LVAD implantation and 6 and 12 months thereafter in 37 adults with end-stage heart failure. Twelve patients received a HeartMate 3, 7 patients received a HeartWare, and 18 patients received a HeartMate II. At baseline, patients had elevated plasma levels of the platelet protein upon activation, ß-thromboglobulin, and active von Willebrand factor in thrombogenic state (VWFa), which remained high after LVAD implantation. Von Willebrand factor levels and VWF activity were elevated at baseline but normalized 12 months after LVAD implantation. High D -dimer plasma levels, at baseline, remained elevated after 12 months. This was associated with an increase in plasma thrombin-antithrombin-complex levels and plasma levels of contact activation marker-cleaved H-kininogen after LVAD implantation. Considering these results it could be concluded that LVAD patients show significant coagulation activation despite antithrombotic therapy, which could explain why patients are at high risk for LVAD-induced thrombosis. Continuous low-grade systemic platelet activation and contact activation may contribute to prothrombotic effects of LVAD.

The use of virtual reality in patient education related to medical somatic treatment: A scoping review.

OBJECTIVE: To map the available evidence on the context, content and outcome of VR in patient education in situations related to preparation for medical somatic treatment. METHODS: A Scoping review. In October 2020, the Embase, CINAHL, MEDLINE and PsycINFO databases were searched with the terms 'Virtual Reality' and 'Patient Education'. The literature was synthesised and mapped with a narrative approach. RESULTS: 17 studies published between 2015 and 2020 were included in the qualitative synthesis. VR was applied in (paediatric) surgery and radiation therapy treatment. VR interventions were heterogeneous regarding technical applications, context of implementation, guidance by healthcare professionals and integration in education sessions. Anxiety reduction was demonstrated significantly in some studies. Patients experienced VR education useful; it enhanced understanding, improved communication with healthcare professionals and encouraged treatment compliance. CONCLUSIONS: The application of VR in patient education is a promising technology. Patients are highly satisfied and experience enhanced understanding. VR education was not effective in reducing all anxiety, pain and stress and improving preparedness for treatment. Practice implications It is important to develop VR interventions profoundly. The application of a methodological framework for VR development is recommended. Involve patients, educationalists and technology professionals in the development of technology interventions.

Patients' voices in the development of pre-surgical patient education using virtual reality: A qualitative study.

Objective: To identify the information needs and perceptions of patients regarding the application of virtual reality in pre-surgical patient education. Methods: A qualitative study was conducted between March and July 2020. The study population consisted of a purposive sample of patients scheduled for cardiac surgery from a single institution. Semi-structured individual interviews (n=19) were conducted and analysed using thematic analysis. Results: Patient perceptions regarding virtual reality and information needs related to hospitalisation and surgery could be categorised into three themes: Creating familiarity, contents to explore and challenges and preconditions. Conclusions: Virtual reality technology is a promising tool that can enhance conventional patient education to improve understanding and to potentially reduce concerns and anxieties. The virtual reality environment creates an opportunity for patients to be in control of the timing, quantity, depth and frequency of patient education. A virtual reality education tool should not be a substitute for personal contact with the physician. Innovation: Patient information needs were identified profoundly to the further development of a virtual reality intervention. This intervention aims to educate patients prior to elective cardiac surgery.

Pirfenidone Has Anti-fibrotic Effects in a Tissue-Engineered Model of Human Cardiac Fibrosis.

A fundamental process in the development and progression of heart failure is fibrotic remodeling, characterized by excessive deposition of extracellular matrix proteins in response to injury. Currently, therapies that effectively target and reverse cardiac fibrosis are lacking, warranting novel therapeutic strategies and reliable methods to study their effect. Using a gelatin methacryloyl hydrogel, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) and human fetal cardiac fibroblasts (hfCF), we developed a multi-cellular mechanically tunable 3D in vitro model of human cardiac fibrosis. This model was used to evaluate the effects of a promising anti-fibrotic drug-pirfenidone-and yields proof-of-concept of the drug testing potential of this platform. Our study demonstrates that pirfenidone has anti-fibrotic effects but does not reverse all TGF-ß1 induced pro-fibrotic changes, which provides new insights into its mechanism of action.

Repetitive Immune-Mediated Noninfectious Endocarditis Necessitating 5 Mitral Valve Replacements.

We present a young patient who had to undergo 5 mitral valve replacements (MVR) because of a repetitive immune-mediated noninfectious endocarditis. The patient was treated with multiple anti-inflammatory drugs and high-dose prednisone. After the fifth MVR, the patient remained in stable condition using Anakinra after 22 months of follow-up. (Level of Difficulty: Advanced.).

A data mining-based cross-industry process for predicting major bleeding in mechanical circulatory support.

Aims: Over a third of patients, treated with mechanical circulatory support (MCS) for end-stage heart failure, experience major bleeding. Currently, the prediction of a major bleeding in the near future is difficult because of many contributing factors. Predictive analytics using data mining could help calculating the risk of bleeding; however, its application is generally reserved for experienced researchers on this subject. We propose an easily applicable data mining tool to predict major bleeding in MCS patients. Methods and results: All data of electronic health records of MCS patients in the University Medical Centre Utrecht were included. Based on the cross-industry standard process for data mining (CRISP-DM) methodology, an application named Auto-Crisp was developed. Auto-Crisp was used to evaluate the predictive models for a major bleeding in the next 3, 7, and 30 days after the first 30 days post-operatively following MCS implantation. The performance of the predictive models is investigated by the area under the curve (AUC) evaluation measure. In 25.6% of 273 patients, a total of 142 major bleedings occurred during a median follow-up period of 542 [interquartile range (IQR) 205-1044] days. The best predictive models assessed by Auto-Crisp had AUC values of 0.792, 0.788, and 0.776 for bleedings in the next 3, 7, and 30 days, respectively. Conclusion: The Auto-Crisp-based predictive model created in this study had an acceptable performance to predict major bleeding in MCS patients in the near future. However, further validation of the application is needed to evaluate Auto-Crisp in other research projects.

Advanced In Vitro Modeling to Study the Paradox of Mechanically Induced Cardiac Fibrosis.

In heart failure, cardiac fibrosis is the result of an adverse remodeling process. Collagen is continuously synthesized in the myocardium in an ongoing attempt of the heart to repair itself. The resulting collagen depositions act counterproductively, causing diastolic dysfunction and disturbing electrical conduction. Efforts to treat cardiac fibrosis specifically have not been successful and the molecular etiology is only partially understood. The differentiation of quiescent cardiac fibroblasts to extracellular matrix-depositing myofibroblasts is a hallmark of cardiac fibrosis and a key aspect of the adverse remodeling process. This conversion is induced by a complex interplay of biochemical signals and mechanical stimuli. Tissue-engineered 3D models to study cardiac fibroblast behavior in vitro indicate that cyclic strain can activate a myofibroblast phenotype. This raises the question how fibroblast quiescence is maintained in the healthy myocardium, despite continuous stimulation of ultimately profibrotic mechanotransductive pathways. In this review, we will discuss the convergence of biochemical and mechanical differentiation signals of myofibroblasts, and hypothesize how these affect this paradoxical quiescence. Impact statement Mechanotransduction pathways of cardiac fibroblasts seem to ultimately be profibrotic in nature, but in healthy human myocardium, cardiac fibroblasts remain quiescent, despite continuous mechanical stimulation. We propose three hypotheses that could explain this paradoxical state of affairs. Furthermore, we provide suggestions for future research, which should lead to a better understanding of fibroblast quiescence and activation, and ultimately to new strategies for the prevention and treatment of cardiac fibrosis and heart failure.

One year improvement of exercise capacity in patients with mechanical circulatory support as bridge to transplantation.

AIMS: Mechanical circulatory support (MCS) results in substantial improvement of prognosis and functional capacity. Currently, duration of MCS as a bridge to transplantation (BTT) is often prolonged due to shortage of donor hearts. Because long-term results of exercise capacity after MCS are largely unknown, we studied serial cardiopulmonary exercise tests (CPETs) during the first year after MCS implantation. METHODS AND RESULTS: Cardiopulmonary exercise tests at 6 and 12 months after MCS implantation in BTT patients were retrospectively analysed, including clinical factors related to exercise capacity. A total of 105 MCS patients (67% male, 50 ± 12 years) underwent serial CPET at 6 and 12 months after implantation. Power (105 ± 35 to 114 ± 40 W; P ≤ 0.001) and peak VO2 per kilogram (pVO2/kg) improved significantly (16.5 ± 5.0 to 17.2 ± 5.5 mL/kg/min (P = 0.008)). Improvement in pVO2 between 6 and 12 months after LVAD implantation was not related to heart failure aetiology or haemodynamic severity prior to MCS. We identified maximal heart rate at exercise as an important factor for pVO2. Younger age and lower BMI were related to further improvement. At 12 months, 25 (24%) patients had a normal exercise capacity (Weber classification A, pVO2 > 20 mL/kg/min). CONCLUSIONS: Exercise capacity (power and pVO2) increased significantly between 6 and 12 months after MCS independent of Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile or heart failure aetiology. Heart rate at exercise importantly relates to exercise capacity. This long-term improvement in exercise capacity is important information for the growing group of long-term MCS patients as this is critical for the quality of life of patients.

Myocardial Disease and Long-Distance Space Travel: Solving the Radiation Problem.

Radiation-induced cardiovascular disease is a well-known complication of radiation exposure. Over the last few years, planning for deep space missions has increased interest in the effects of space radiation on the cardiovascular system, as an increasing number of astronauts will be exposed to space radiation for longer periods of time. Research has shown that exposure to different types of particles found in space radiation can lead to the development of diverse cardiovascular disease via fibrotic myocardial remodeling, accelerated atherosclerosis and microvascular damage. Several underlying mechanisms for radiation-induced cardiovascular disease have been identified, but many aspects of the pathophysiology remain unclear. Existing pharmacological compounds have been evaluated to protect the cardiovascular system from space radiation-induced damage, but currently no radioprotective compounds have been approved. This review critically analyzes the effects of space radiation on the cardiovascular system, the underlying mechanisms and potential countermeasures to space radiation-induced cardiovascular disease.