Truncated titin is structurally integrated into the human dilated cardiomyopathic sarcomere.

Heterozygous (HET) truncating variant mutations in the TTN gene (TTNtvs), encoding the giant titin protein, are the most common genetic cause of dilated cardiomyopathy (DCM). However, the molecular mechanisms by which TTNtv mutations induce DCM are controversial. Here, we studied 127 clinically identified DCM human cardiac samples with next-generation sequencing (NGS), high-resolution gel electrophoresis, Western blot analysis, and super-resolution microscopy in order to dissect the structural and functional consequences of TTNtv mutations. The occurrence of TTNtv was found to be 15% in the DCM cohort. Truncated titin proteins matching, by molecular weight, the gene sequence predictions were detected in the majority of the TTNtv+ samples. Full-length titin was reduced in TTNtv+ compared with TTNtv- samples. Proteomics analysis of washed myofibrils and stimulated emission depletion (STED) super-resolution microscopy of myocardial sarcomeres labeled with sequence-specific anti-titin antibodies revealed that truncated titin was structurally integrated into the sarcomere. Sarcomere length-dependent anti-titin epitope position, shape, and intensity analyses pointed at possible structural defects in the I/A junction and the M-band of TTNtv+ sarcomeres, which probably contribute, possibly via faulty mechanosensor function, to the development of manifest DCM.

Hormonal changes in the first 24 postoperative hours after cardiac surgical procedures.

Background: Hormone level changes after heart surgeries are a widely observed phenomenon due to neurohormonal feedback mechanisms that may affect postoperative morbidity and mortality. The current study aimed to analyze the changes in thyroid and sex hormones in the first 24 postoperative hours after heart surgery. Methods: This prospective, observational study (registered on ClinicalTrials.gov: NCT03736499; 09/11/2018) included 49 patients who underwent elective cardiac surgical procedures at a tertiary heart center between March 2019 and December 2019. Thyroid hormones, including thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4), and sex hormones, including prolactin (PRL) and total testosterone, were measured preoperatively and at 24 h postoperatively. Results: Significant decreases in serum TSH (P < 0.001), T3 (P < 0.001) and total testosterone (P < 0.001) levels were noted, whereas T4 (P = 0.554) and PRL (P = 0.616) did not significantly change. Intensive care unit (ICU) hours (P < 0.001), mechanical ventilation (P < 0.001) and Vasoactive-Inotropic Score (VIS) (P = 0.006) were associated with postoperative T3 level. ICU hours were associated with postoperative T4 level (P = 0.028). Postoperative and delta testosterone levels were in connection with lengths of stay in ICU (P = 0.032, P = 0.010 respectively). Model for End-Stage Liver Disease (MELD) scores were associated with thyroid hormone levels and serum testosterone. Conclusions: T3 may represent a marker of nonthyroidal illness syndrome and testosterone may reflect hepatic dysfunction. In addition, PRL may act as a stress hormone in female patients.

Nanoscale Structural Comparison of Fibrillin-1 Microfibrils Isolated from Marfan and Non-Marfan Syndrome Human Aorta.

Fibrillin-1 microfibrils are essential elements of the extracellular matrix serving as a scaffold for the deposition of elastin and endowing connective tissues with tensile strength and elasticity. Mutations in the fibrillin-1 gene (FBN1) are linked to Marfan syndrome (MFS), a systemic connective tissue disorder that, besides other heterogeneous symptoms, usually manifests in life-threatening aortic complications. The aortic involvement may be explained by a dysregulation of microfibrillar function and, conceivably, alterations in the microfibrils' supramolecular structure. Here, we present a nanoscale structural characterization of fibrillin-1 microfibrils isolated from two human aortic samples with different FBN1 gene mutations by using atomic force microscopy, and their comparison with microfibrillar assemblies purified from four non-MFS human aortic samples. Fibrillin-1 microfibrils displayed a characteristic "beads-on-a-string" appearance. The microfibrillar assemblies were investigated for bead geometry (height, length, and width), interbead region height, and periodicity. MFS fibrillin-1 microfibrils had a slightly higher mean bead height, but the bead length and width, as well as the interbead height, were significantly smaller in the MFS group. The mean periodicity varied around 50-52 nm among samples. The data suggest an overall thinner and presumably more frail structure for the MFS fibrillin-1 microfibrils, which may play a role in the development of MFS-related aortic symptomatology.

[Complex endovascular repairs of the aortic arch.] / Komplex endovascularis rekonstrukciók az aortaíven.

Thoracic endovascular aneurysm repair (TEVAR) of the aortic arch has started to spread in recent years. We present our initial experience with TEVAR involving supra-aortic branches using parallel and branched grafts. Parallel grafts are typically used in emergency cases. In the case of Z0 proximal fixation, we can perform a combined hybrid surgery with Z1 debranching and securing of the innominate artery with chimney graft, which can also be used instead of Z0 debranching when the patient is unfit for sternotomy. In the case of TEVAR with planned Z2 position with inadvertent covering of the left common carotid artery, we can perform chimney conversion to rapidly recover the circulation of the left common carotid artery (LCCA). Instead of prior revascularization of the left subclavian artery, chimney graft can be used to recover the lumen, in the case of left upper limb ischemia after Z2 TEVAR. Exclusion of penetrating aortic ulcers located in the lesser curvature can be facilitated by use of a custom-made graft, where a scallop is placed around the origin of the supra-aortic vessel, thus increasing the length of the proximal neck. For elective interventions, custom-made branching grafts can be allowed to save all three branches with Z0 fixation. Technical success was obtained in all cases. Orv Hetil. 2023; 164(11): 426-431.

Staged Hybrid Repair of a Complex Type B Aortic Dissection.

Due to its heterogeneous clinical picture and lengthy evolution, the management of type B aortic dissection represents a clinical challenge, often calling for complex strategies combining medical, endovascular, and open surgical strategies. We present the case of a 45-year-old female who had previously suffered a complicated type B aortic dissection requiring a femoro-femoral crossover bypass and further conservative treatment. Seven years later, due to an aneurysmal development, a staged descending aortic management was strategized, beginning with the implantation of a frozen elephant trunk device due to an insufficient proximal landing zone for endovascular repair. However, the development of a distal stent graft-induced new entry complicated the dissection and led to the formation of a second false lumen, thus prompting an expedited hybrid reconstruction. We describe a hybrid repair strategy tailored to the patient's particular aortic anatomic conformation, combining ilio-visceral debranching and thoracic endovascular aortic repair. Due to a lack of consensus on the ideal management strategy for type B aortic dissection, an individualized approach conducted by an experienced aortic team may generate the best outcome. The appropriate timing and planning of the intervention are the keys to successful results in complex type B aortic dissection cases with an elaborate anatomic conformation.

3D culturing of human pluripotent stem cells-derived endothelial cells for vascular regeneration.

Rationale: Human induced pluripotent stem cell-derived endothelial cells can be candidates for engineering therapeutic vascular grafts. Methods: Here, we studied the role of three-dimensional culture on their characteristics and function both in vitro and in vivo. Results: We found that differentiated hPSC-EC can re-populate decellularized biomatrices; they remain viable, undergo maturation and arterial/venous specification. Human PSC-EC develop antifibrotic, vasoactive and anti-inflammatory properties during recellularization. In vivo, a robust increase in perfusion was detected at the engraftment sites after subcutaneous implantation of an hPSC-EC-laden hydrogel in rats. Histology confirmed survival and formation of capillary-like structures, suggesting the incorporation of hPSC-EC into host microvasculature. In a canine model, hiPSC-EC-seeded onto decellularised vascular segments were functional as aortic grafts. Similarly, we showed the retention and maturation of hiPSC-EC and dynamic remodelling of the vessel wall with good maintenance of vascular patency. Conclusions: A combination of hPSC-EC and biomatrices may be a promising approach to repair ischemic tissues.

Poor Preoperative Nutritional Status, but Not Hormone Levels, Are Associated With Mortality After Cardiac Surgery.

OBJECTIVES: The authors' aim was to examine the preoperative hormone and nutritional status in patients undergoing elective cardiac surgery. DESIGN AND SETTINGS: The authors' research was a single-center, prospective, observational study (ClinicalTrials.gov: NCT03736499). PARTICIPANTS & INTERVENTIONS: The authors examined 252 patients who underwent elective cardiac surgery. Preoperative thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), prolactin, and testosterone levels were collected and analyzed after the surgery. The Geriatric Nutritional Risk Index (GNRI), Controlling Nutritional Status (CONUT), and Prognostic Nutritional Index (PNI) were all calculated as a sum and groups. Frailty was calculated based on the modified Frailty Index-11. The primary outcome was overall mortality. MEASUREMENTS AND MAIN RESULTS: The mean age of the patients was 64.23 years (standard deviation: 11.07 years). Thirty-three patients (13.01%) died during the median follow-up time of 20.48 months (interquartile range: 18.90-22.98 months). Thyroid hormones were examined as continuous variables and also in 3 groups based on low, normal, and high hormone levels. Continuous TSH (p = 0.230), continuous fT3 (p = 0.492), and continuous fT4 (p = 0.657) were not significantly associated with total mortality. After adjustment for the European System for Cardiac Operative Risk Evaluation II and postoperative complications, the following nutritional scores were associated with total mortality: GNRI < 91 (adjusted hazard ratio [AHR]: 4.384; 95% confidence interval [CI]: 1.866-10.303, p = 0.001), the higher CONUT group (AHR: 1.736; 95% CI: 1.736-2.866, p = 0.031), and a PNI < 48 points (AHR: 3.465; 95% CI: 1.735-6.918, p < 0.001). The modified Frailty Index-11 was not associated with mortality. CONCLUSIONS: Before cardiac surgery, nutritional status should be assessed because the findings may help to decrease mortality. The hormone levels were not associated with mortality.

"Turtle cage" method in the cardiac surgical treatment of constrictive pericarditis ­ our short-term results / "Turtle cage" módszer a pericarditis constrictiva szívsebészeti kezelésében - rövid távú eredményeink.

Összefoglaló. Bevezetés: A pericarditis constrictiva egy krónikus gyulladásos folyamat révén kialakuló betegség, melynek során a pericardium elveszíti rugalmasságát, gátolja a szív muködését, végso soron szívelégtelenséghez vezet. Egyetlen oki terápiája sebészi. A mutéti megoldásként legelterjedtebben alkalmazott teljes pericardiectomia hosszú idotartamú mutét, amely akár 18%-os mutéti kockázattal járhat, és amelyhez az esetek jelentos részében szívmotor alkalmazása szükséges. Célkituzés: Egy, az irodalomból már ismert, de csak ritkán és a legtöbbször csak a hagyományos pericardiectomia kiegészítéseként alkalmazott mutéti eljárás, a "turtle cage" pericardiectomia hatásosságának, eredményeinek, lehetséges elonyeinek vizsgálata. Módszer: 2008 és 2021 között Klinikánkon 33 "turtle cage" mutétet végeztünk pericarditis constrictiva miatt. A posztoperatív 30 napos idoszak eredményeit több, a nemzetközi irodalomban megjelent közlemény adataival hasonlítottuk össze. Eredmények: Az intraoperatív kép alapján minden esetben sikeres volt a beavatkozás, a 33 beteg egyikénél sem volt szükség szívmotor alkalmazására (0%), szemben a vizsgált közleményekkel. A 33 beavatkozás során 1 beteget veszítettünk el (3%), valamint 1 páciensnél volt szükség vérzés miatti reoperációra (3%), 4 betegnél dialízisre (12,1%). Ezen eredményeink összevethetok a nagy esetszámot felvonultató közleményekkel, és szignifikánsan jobbak az egyik megjelenített európai centrum eredményeinél. Következtetés: Az általunk alkalmazott "turtle cage" pericardiectomia önmagában is megfelelo eljárás a pericarditis constrictiva szívsebészeti kezelésére. Alkalmazásával minimalizálható a szívmotor használatának szükségessége, ezáltal a mutéti kockázat. Eredményeink a technikának köszönhetoen még a nagy esetszámú, sok tapasztalattal rendelkezo centrumok eredményeivel is összevethetok, azokkal megegyezok. Orv Hetil. 2022; 163(10): 393-399. INTRODUCTION: Constrictive pericarditis is a disease caused by a chronic inflammatory process, which is characterized by the pericardium's loss of flexibility, inhibiting the function of the heart, ultimately causing heart failure. The only definitive therapy is surgical. Total pericardiectomy, which is the most common surgical approach, is a lengthy procedure with up to 18% operative risk, and it often requires the use of cardiopulmonary bypass. OBJECTIVE: The evaluation of the effectiveness, results and possible advantages of a surgical technique, "turtle cage" pericardiectomy, which is described in the literature, although rarely used, mainly in addition to conventional pericardiectomy. METHOD: Between 2008 and 2021, we performed 33 "turtle cage" procedures on patients with constrictive pericarditis in our Institute. We compared the results of the 30-day postoperative period with internationally published data from multiple sources. RESULTS: Based on intraoperative findings, the procedure was successful in all cases, there were no instances when the use of cardiopulmonary bypass was required (0%). During the 33 procedures, we lost 1 patient (3%), reoperation was necessary for postoperative bleeding in 1 case (3%), and postoperative dialysis was necessary in 4 cases (12.1%). These results are comparable to those published by high-volume centres, and significantly better than those of one of the European centres published. CONCLUSION: The "turtle cage" pericardiectomy, as performed in our Institute, is suitable for the treatment of constrictive pericarditis on its own. With its use, we were able to minimize the use of cardiopulmonary bypass and the operative risk. Our results with this technique are comparable to those of the high-volume, highly experienced centres. Orv Hetil. 2022; 163(10): 393-399.

Blood-filled cyst of the tricuspid valve: Multiple cardiac disorders, one surgical case.

BACKGROUND: Intracardiac blood cysts are an exceedingly rare occurrence in adulthood. Detailed imaging modalities aid in the diagnosis of such incidental lesions and procedure planning. METHODS: We report the case of a 51-year-old male accusing dyspnea on exertion as a sole symptom which led to the discovery of multiple cardiac anomalies, namely, severe aortic valve insufficiency on a bicuspid aortic valve, ascending aortic aneurysm, a cystic mass on the tricuspid valve, patent foramen ovale, and an occluded right coronary artery. RESULTS: The disorders were managed in a single surgical intervention, the resected mass being confirmed as a blood cyst. CONCLUSIONS: Our case presents a unique association of cardiac disorders, including a highly uncommon intracardiac blood-filled cyst, and underlines the importance of multimodality imaging and interdisciplinary approach in the successful management of such complex cases.

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.

Predictors of mortality following extracorporeal membrane oxygenation support in an unselected, critically ill patient population.

INTRODUCTION: Mechanical circulatory support (MCS) has been established as a means of augmenting circulation in patients with critically decreased systolic function due to a variety of underlying clinical reasons. Different methods of MCS may be used, with the venous-arterial extracorporeal membrane oxygenation system (VA-ECMO) being one of the most utilized devices in everyday care. AIM: To determine independent predictors influencing mortality outcomes following VA-ECMO therapy in a large, unselected, adult, critically ill patient population in cardiogenic shock (CS). MATERIAL AND METHODS: Data on 235 consecutive, real-world VA-ECMO treatments were assessed. Analysis was conducted for all subjects requiring MCS with the VA-ECMO as the first instalment, regardless of underlying cause or eventual upgrade. All potential clinical factors influencing mortality were examined and evaluated. RESULTS: Overall mortality was ~66% at median 28 days follow-up and significantly depended upon pH < 7.3 (HR = 3.56; p < 0.001), and age ≥ 65 years (HR = 1.96; p = 0.001). Acute coronary syndrome (ACS) as an indication for VA-ECMO displayed a nearly significant value (HR = 1.44; p = 0.07). Heart transplant (hTX) primary graft failure as an indication for the VA-ECMO displayed a clearly favorable outcome (HR = 0.51, p = 0.025); all data based on multivariate Cox regression analysis. CONCLUSIONS: Mortality in patients requiring VA-ECMO remains high. We conclude that only decreased pH values and advanced age clearly influence mortality in this MCS scenario. ACS also bodes unfavorably, whereas hTX as an indication clearly shows better survival.

Changes in the SARS-CoV-2 cellular receptor ACE2 levels in cardiovascular patients: a potential biomarker for the stratification of COVID-19 patients.

Angiotensin-converting enzyme 2 (ACE2) is essential for SARS-CoV-2 cellular entry. Here we studied the effects of common comorbidities in severe COVID-19 on ACE2 expression. ACE2 levels (by enzyme activity and ELISA measurements) were determined in human serum, heart and lung samples from patients with hypertension (n = 540), heart transplantation (289) and thoracic surgery (n = 49). Healthy individuals (n = 46) represented the controls. Serum ACE2 activity was increased in hypertensive subjects (132%) and substantially elevated in end-stage heart failure patients (689%) and showed a strong negative correlation with the left ventricular ejection fraction. Serum ACE2 activity was higher in male (147%), overweight (122%), obese (126%) and elderly (115%) hypertensive patients. Primary lung cancer resulted in higher circulating ACE2 activity, without affecting ACE2 levels in the surrounding lung tissue. Male sex resulted in elevated serum ACE2 activities in patients with heart transplantation or thoracic surgery (146% and 150%, respectively). Left ventricular (tissular) ACE2 activity was unaffected by sex and was lower in overweight (67%), obese (62%) and older (73%) patients with end-stage heart failure. There was no correlation between serum and tissular (left ventricular or lung) ACE2 activities. Neither serum nor tissue (left ventricle or lung) ACE2 levels were affected by RAS inhibitory medications. Abandoning of ACEi treatment (non-compliance) resulted in elevated blood pressure without effects on circulating ACE2 activities. ACE2 levels associate with the severity of cardiovascular diseases, suggestive for a role of ACE2 in the pathomechanisms of cardiovascular diseases and providing a potential explanation for the higher mortality of COVID-19 among cardiovascular patients. Abandoning RAS inhibitory medication worsens the cardiovascular status without affecting circulating or tissue ACE2 levels.

Cardiac PANK1 deletion exacerbates ventricular dysfunction during pressure overload.

Coenzyme A (CoA) is an essential cofactor required for intermediary metabolism. Perturbations in homeostasis of CoA have been implicated in various pathologies; however, whether CoA homeostasis is changed and the extent to which CoA levels contribute to ventricular function and remodeling during pressure overload has not been explored. In this study, we sought to assess changes in CoA biosynthetic pathway during pressure overload and determine the impact of limiting CoA on cardiac function. We limited cardiac CoA levels by deleting the rate-limiting enzyme in CoA biosynthesis, pantothenate kinase 1 (Pank1). We found that constitutive, cardiomyocyte-specific Pank1 deletion (cmPank1-/-) significantly reduced PANK1 mRNA, PANK1 protein, and CoA levels compared with Pank1-sufficient littermates (cmPank1+/+) but exerted no obvious deleterious impact on the mice at baseline. We then subjected both groups of mice to pressure overload-induced heart failure. Interestingly, there was more ventricular dilation in cmPank1-/- during the pressure overload. To explore potential mechanisms contributing to this phenotype, we performed transcriptomic profiling, which suggested a role for Pank1 in regulating fibrotic and metabolic processes during the pressure overload. Indeed, Pank1 deletion exacerbated cardiac fibrosis following pressure overload. Because we were interested in the possibility of early metabolic impacts in response to pressure overload, we performed untargeted metabolomics, which indicated significant changes to metabolites involved in fatty acid and ketone metabolism, among other pathways. Collectively, our study underscores the role of elevated CoA levels in supporting fatty acid and ketone body oxidation, which may be more important than CoA-driven, enzyme-independent acetylation in the failing heart.NEW & NOTEWORTHY Changes in CoA homeostasis have been implicated in a variety of metabolic diseases; however, the extent to which changes in CoA homeostasis impacts remodeling has not been explored. We show that limiting cardiac CoA levels via PANK deletion exacerbated ventricular remodeling during pressure overload. Our results suggest that metabolic alterations, rather than structural alterations, associated with Pank1 deletion may underlie the exacerbated cardiac phenotype during pressure overload.

Human Tissue Angiotensin Converting Enzyme (ACE) Activity Is Regulated by Genetic Polymorphisms, Posttranslational Modifications, Endogenous Inhibitors and Secretion in the Serum, Lungs and Heart.

Objective: Inhibitors of the angiotensin converting enzyme (ACE) are the primarily chosen drugs to treat heart failure and hypertension. Moreover, an imbalance in tissue ACE/ACE2 activity is implicated in COVID-19. In the present study, we tested the relationships between circulating and tissue (lung and heart) ACE levels in men. Methods: Serum, lung (n = 91) and heart (n = 72) tissue samples were collected from Caucasian patients undergoing lung surgery or heart transplantation. ACE I/D genotype, ACE concentration and ACE activity were determined from serum and tissue samples. Clinical parameters were also recorded. Results: A protocol for ACE extraction was developed for tissue ACE measurements. Extraction of tissue-localized ACE was optimal in a 0.3% Triton-X-100 containing buffer, resulting in 260 ± 12% higher ACE activity over detergent-free conditions. SDS or higher Triton-X-100 concentrations inhibited the ACE activity. Serum ACE concentration correlated with ACE I/D genotype (II: 166 ± 143 ng/mL, n = 19, ID: 198 ± 113 ng/mL, n = 44 and DD: 258 ± 109 ng/mL, n = 28, p < 0.05) as expected. In contrast, ACE expression levels in the lung tissue were approximately the same irrespective of the ACE I/D genotype (II: 1423 ± 1276 ng/mg, ID: 1040 ± 712 ng/mg and DD: 930 ± 1273 ng/mg, p > 0.05) in the same patients (values are in median ± IQR). Moreover, no correlations were found between circulating and lung tissue ACE concentrations and activities (Spearman's p > 0.05). In contrast, a significant correlation was identified between ACE activities in serum and heart tissues (Spearman's Rho = 0.32, p < 0.01). Finally, ACE activities in lung and the serum were endogenously inhibited to similar degrees (i.e., to 69 ± 1% and 53 ± 2%, respectively). Conclusion: Our data suggest that circulating ACE activity correlates with left ventricular ACE, but not with lung ACE in human. More specifically, ACE activity is tightly coordinated by genotype-dependent expression, endogenous inhibition and secretion mechanisms.

Fenestrated endovascular repair of a thoracoabdominal aortic aneurysm in chronic dissection / Krónikus aortadissectio talaján kialakult thoracoabdominalis aneurysma endovascularis kezelése fenesztrált sztentgrafttal.

Összefoglaló. Az aortadissectio krónikus stádiumában kialakuló thoracoabdominalis tágulatok megoldása multidiszciplináris megközelítést, nagy felkészültséget és fejlett technológiát igényel. A jellemzoen többlépcsos mutétsorozat mortalitása és morbiditása az endovascularis technológia fejlodésével csökkent, de még mindig jelentos. A fenesztrált endovascularis aortamutét a thoracoabdominalis nyitott mutét alternatívája, mely kisebb mortalitással és morbiditással, rövidebb kórházi tartózkodással jár. Aortadissectio esetén történo alkalmazása az aorta lumenében lévo membrán miatt kihívást jelent. Esetbemutatásunkban egy 56 éves nobeteget demonstrálunk, aki tíz évvel korábban A-típusú dissectio miatt aorta ascendens rekonstrukción esett át. A követés során csaknem a teljes aorta tágulata alakult ki, melynek megoldása három lépésben történt. Az elso lépésben a disszekált aortaív nyitott mutétjét végeztük 'frozen elephant trunk' technikával, majd az aorta descendens tágulatának endovascularis kezelése történt sztentgraft-implantációval. A mutétsorozat záró lépése egy fenesztrált endovascularis aortamutét volt, mely egyben ezen technikának az aortadissectio esetében történt elso hazai alkalmazását jelenti. Orv Hetil. 2021; 162(31): 1260-1264. Summary. Thoracoabdominal aortic aneurysms developing in the chronic phase of an aortic dissection require multidisciplinary approach, experienced operators and advanced technology. The mortality and morbidity rate of these multistage operations were reduced with the latest technical achievements in endovascular repair, but they are still significant. Fenestrated endovascular aortic repair, an alternative of thoracoabdominal open repair, is associated with less mortality and morbidity, shorter hospital stay. Using fenestrated devices in aortic dissection is usually technically demanding due to the dissection membrane. We report the case of a 56-year-old woman, who underwent ascending aortic repair due to type A aortic dissection. During the follow-up, a large thoracoabdominal aneurysm developed involving also the arch. We performed a three-stage operation starting with the open repair of the aortic arch using a 'frozen elephant trunk' device followed by a thoracic endovascular aortic repair of the descending aorta. The final stage was a fenestrated endovascular aortic repair, which is the first use of this technique in aortic dissection in Hungary. Orv Hetil. 2021; 162(31): 1260-1264.

Pseudoaneurysm of the ascending aorta: case report of a donor-derived Pseudomonas infection in a heart transplant recipient.

BACKGROUND: Mycotic aortic pseudoaneurysm is a rare complication after heart transplantation (HTX) with remarkable mortality. Intrathoracic infection is a well-documented predisposing factor for this disease. Staphylococcus aureus, Pseudomonas aeruginosa or Candida species are commonly isolated from resected specimens of the pseudoaneurysms. We demonstrate a unique case of mycotic pseudoaneurysm caused by presumably donor-derived Pseudomonas infection in a heart transplant recipient. CASE PRESENTATION: Our 67-year-old male patient treated with diabetes mellitus underwent HTX. The donor suffered from epiglottic abscess and pneumonia with known microorganisms including Pseudomonas, therefore both the donor and recipient received targeted antimicrobial therapy and prophylaxis. Five months after the uneventful HTX, lab test of the asymptomatic patient showed moderate, increasing C-reactive protein level without obviuos source of infection. Chest computed tomography showed a large (90 mm) saccular dilatation of the tubular portion of ascending aorta. Urgent surgical intervention identified a pseudoaneurysm, histological examinations and cultures of the resected aorta verified Pseudomonas aeruginosa aortitis, while all blood cultures remained negative. Retrospective interrogation of other transplanted organs of the donor supported donor-derived infection as the transport fluid of the right kidney grew Pseudomonas. The patient received 3 weeks of ceftazidime followed by 7 months of oral ciprofloxacin therapy. One year after the operation the patient was asymptomatic with normal inflammatory markers. CONCLUSIONS: Donor-derived infection is a rare but potential cause of aortitis. Early diagnosis, surgical intervention and adjuvant antibiotic therapy seem to be the keys to successful management of mycotic pseudoaneurysms after HTX.

Case Report: Morphological Characterization and Long-Term Observation of Bilateral Sequential Internal Mammary Artery Aneurysms in a Patient With Confirmed FBN1 Mutation.

Marfan syndrome (MFS) is a genetically determined connective tissue disorder that leads to ocular, skeletal, and severe cardiovascular involvement. High mortality of MFS is associated with aortic dissection and aneurysm characteristic to the syndrome. In MFS, only a few cases of peripheral arterial involvement have been reported so far, mostly without a genetically confirmed diagnosis. We report a 41-year-old MFS patient with a saccular pearl-string-like aneurysm on the right internal mammary artery (RIMA) and a single aneurysm on the left internal mammary artery (LIMA). To our knowledge this is the first reported case on internal mammary artery aneurysms with this special morphology and with follow-up and blood pressure control as primary therapeutic approach in a patient with genetically confirmed MFS. The aneurysms with the above described morphology first appeared as small aneurysms on a CT scan 6 years after a cardiac operation. Due to the lack of guidelines, based on the asymptomatic state of the patient, the increased tortuosity of the affected vessels and the history of prior cardiac surgery, we decided to closely monitor these aneurysms with blood pressure control and without carrying out any interventions. On the CT scans done 3, 11, 12, 17, and 32 months after identifying the aneurysms, no progression of these structures was detected. Our findings confirm the possibility of the occurrence of internal mammary artery aneurysms in patients with FBN1 mutation and we believe that monitoring these aneurysms with blood pressure management can be a suitable option in selected cases.

The Many Lives of a Complex Marfan Syndrome Patient: Staged Therapeutic Decisions.

We present a complex Marfan case, with previous type A aortic dissection, subsequent progressing aortic arch aneurysm, type B chronic aortic dissection, and Barlow disease with severe mitral regurgitation, all expressions of the same phenotype, all needing staged complex surgical therapies. (Level of Difficulty: Intermediate.).

Potential predictors of severe cardiovascular involvement in Marfan syndrome: the emphasized role of genotype-phenotype correlations in improving risk stratification-a literature review.

BACKGROUND: Marfan syndrome (MFS) is a genetically determined systemic connective tissue disorder, caused by a mutation in the FBN1 gene. In MFS mainly the cardiovascular, musculoskeletal and ocular systems are affected. The most dangerous manifestation of MFS is aortic dissection, which needs to be prevented by a prophylactic aortic root replacement. MAIN BODY: The indication criteria for the prophylactic procedure is currently based on aortic diameter, however aortic dissections below the threshold defined in the guidelines have been reported, highlighting the need for a more accurate risk stratification system to predict the occurrence of aortic complications. The aim of this review is to present the current knowledge on the possible predictors of severe cardiovascular manifestations in MFS patients, demonstrating the wide range of molecular and radiological differences between people with MFS and healthy individuals, and more importantly between MFS patients with and without advanced aortic manifestations. These differences originating from the underlying common molecular pathological processes can be assessed by laboratory (e.g. genetic testing) and imaging techniques to serve as biomarkers of severe aortic involvement. In this review we paid special attention to the rapidly expanding field of genotype-phenotype correlations for aortic features as by collecting and presenting the ever growing number of correlations, future perspectives for risk stratification can be outlined. CONCLUSIONS: Data on promising biomarkers of severe aortic complications of MFS have been accumulating steadily. However, more unifying studies are required to further evaluate the applicability of the discussed predictors with the aim of improving the risk stratification and therefore the life expectancy and quality of life of MFS patients.

Changing strategies in aortic root reconstruction in Marfan syndrome / Stratégiai szemléletváltás a Marfan-szindrómás betegeken végzett aortagyök-rekonstrukciókban.

Összefoglaló. Bevezetés: A Marfan-szindróma autoszomális domináns módon öröklodo, szisztémás kötoszöveti betegség. A hosszú távú túlélés szempontjából fontos a nagyérkatasztrófák megelozése. Szívsebészeti szempontból a legfontosabb elváltozás az aortagyök tágulata. Aortagyök-rekonstrukciós beavatkozásaink Bentall-DeBono-, David I. és módosított Yacoub-mutétek, melyek mind preventív jelleggel, mind dissectio esetén jó eredménnyel végezhetok. Célkituzés: A marfanos betegeknél eltéro technikával végzett aortagyök-rekonstrukciós mutéteink összehasonlítása. Módszer: A Semmelweis Egyetem Városmajori Szív- és Érgyógyászati Klinikáján 1993 és 2020 között Marfan-szindrómásoknál elvégzett Bentall-DeBono-, David I. és módosított Yacoub-féle aortagyök-rekonstrukciókat elemeztük. A mutét szerinti csoportok életkora a beavatkozás idején 29,69 (21,98-41,25) év, 29,15 ± 11,99 év és 35,29 ± 14,14 év volt, a fenti sorrendben. Az adatok forrásául a Magyar Marfan Regiszter és az Aortagyök-rekonstrukciós Regiszter szolgált. Eredmények: Az utánkövetési ido 132 ± 81,04 hónap volt a Bentall-, 76 ± 27,77 hónap a David-, valamint 4,5 (0,75-11,75) hónap a Yacoub-mutét esetén. A David- és a Yacoub-beavatkozások gyakrabban voltak profilaktikusak, mint a Bentall-operációk (p = 0,0153; p = 0,0085). A Bentall-mutéteknél ritkább volt a primer mutét esetleges késobbi elégtelenségébol fakadó reoperáció, mint a David-operációknál (p<0,001). David-beavatkozásnál a Bentall-mutéthez képest hosszabb volt a cardiopulmonaris bypass (p = 0,0013) és az aortalefogás ideje (p = 0,0048), valamint David- és Yacoub-mutét esetén gyakrabban lépett fel korai posztoperatív szövodmény, mint Bentall-operációnál (p = 0,0005; p = 0,0037). A késoi szövodmények és a túlélés tekintetében a csoportok nem különböztek. Következtetés: Marfan-szindrómában a leggyakrabban halált okozó szövodmény az akut aortaruptura, illetve akut aortadissectio. Eredményeink alapján mindhárom profilaktikus aortagyök-rekonstrukciós mutéti típus jól reprodukálható és jó eredménnyel végezheto Marfan-szindrómában. Orv Hetil. 2021; 162(18): 696-704. INTRODUCTION: Marfan syndrome is an autosomal dominant, systemic connective tissue disorder. Preventing vascular complications is essential for long-term survival. Aortic dilation is the main cardiac surgical manifestation. Bentall-DeBono, David I and modified Yacoub aortic root reconstructions treat and prevent aortic dissections with great outcomes. OBJECTIVE: Comparing results of aortic root reconstructions in Marfan syndrome. METHOD: We analysed the data of Bentall-DeBono, David I and modified Yacoub operations performed in Marfan syndrome at the Heart and Vascular Center, Semmelweis University between 1993 and 2020. Ages of surgical groups at the time of operation were 29.69 (21.98-41.25) years, 29.15 ± 11.99 years and 35.29 ± 14.14 years, respectively. Data were obtained from the Hungarian Marfan Register and the Aortic Root Reconstruction Register. RESULTS: Follow-up time was 132 ± 81.04 months for Bentall, 76 ± 27.77 months for David and 4.5 (0.75-11.75) months for Yacoub groups. David and Yacoub operations were prophylactic more frequently than Bentall ones (p = 0.0153; p = 0.0085). Freedom from reoperation after primary surgery insufficiency was more common for Bentall than for David procedure (p<0.001). Compared to Bentall, David surgeries required longer cardiopulmonary bypass (p = 0.0013) and aortic cross clamp time (p = 0.0048), more early postoperative complications occurred after David and Yacoub, than after Bentall operations (p = 0.0005; p = 0.0037). Late complications and survival did not differ among the groups. CONCLUSION: In Marfan syndrome, acute aortic rupture and dissection are the main contributors to mortality. Based on our results, the prophylactic aortic root reconstructions are reproducible and can be performed with great outcomes. Orv Hetil. 2021; 162(18): 696-704.