The completeness of the left atrial appendage amputation during routine cardiac surgery.

BACKGROUND: Left atrial appendage (LAA) is the origin of most heart thrombi which can lead to stroke or other cerebrovascular event in patients with non-valvular atrial fibrillation (AF). This study aimed to prove safety and low complication rate of surgical LAA amputation using cut and sew technique with control of its effectiveness. METHODS: 303 patients who have undergone selective LAA amputation were enrolled in the study in a period from 10/17 to 08/20. The LAA amputation was performed concomitant to routine cardiac surgery on cardiopulmonary bypass with cardiac arrest with or without previous history of AF. The operative and clinical data were evaluated. Extent of LAA amputation was examined intraoperatively by transoesophageal echocardiography (TEE). Six months in follow up, the patients were controlled regarding clinical status and episodes of strokes. RESULTS: Average age of study population was 69.9 ± 19.2 and 81.9% of patients were male. In only three patients was residual stump after LAA amputation larger than 1 cm with average stump size 0.28 ± 0.34 cm. 3 patients (1%) developed postoperative bleeding. Postoperatively 77 (25.4%) patients developed postoperative AF (POAF), of which 29 (9.6%) still had AF at discharge. On 6 months follow up only 5 patients had NYHA class III and 1 NYHA class IV. Seven patients reported with leg oedema and no patient experienced any cerebrovascular event in early postoperative follow up. CONCLUSION: LAA amputation can be performed safely and completely leaving minimal to no LAA residual stump.

Subacute Aortic Rupture Due to Mechanical Chest Compression with Indwelling Impella.

Mechanical cardiopulmonary resuscitation (CPR) devices like Lund University Cardiopulmonary Assist System (LUCAS) cause more skeletal and visceral injuries than standard CPR. A 62-year-old woman with ST-elevation myocardial infarction was resuscitated with LUCAS and Impella CP for refractory cardiogenic shock during percutaneous coronary intervention. She suffered delayed ascending aortic rupture necessitating supracommissural ascending aortic replacement plus triple bypass grafting. Prolonged mechanical CPR with concomitant Impella may lead to aortic rupture. The combined use of LUCAS and Impella may have disastrous consequences.

Benefits of Intra-Aortic Balloon Pump Support in Patients with Postcardiotomy Shock Requiring Venoarterial Extracorporeal Membrane Oxygenation.

BACKGROUND: The benefit of the combined use of an intra-aortic balloon pump (IABP) and venoarterial extracorporeal membrane oxygenation (VA-ECMO) for postcardiotomy shock remains unclear. We aimed to analyse the potential benefits and safety of combining these two devices. METHODS: We enrolled 200 patients treated with either VA-ECMO only or in combination with IABP (ECMO-I group) between January 2012 and January 2021. To adjust the patients' backgrounds, we used propensity score matching for additional analyses, resulting in 57 pairs. The primary endpoint was 30-day survival. Secondary endpoints included successful weaning and complication rates. We also analysed hemodynamic parameters in both groups. RESULTS: After propensity score matching, 30-day survival was better in the ECMO-I group (log-rank p = 0.004). The ECMO-I and ECMO-only groups differed regarding the secondary endpoints, including successful weaning (50.9% and 26.3%, respectively; p = 0.012) and the need for continuous renal replacement therapy (28.1% and 50.9%, p = 0.021). Complication rates were not statistically different between the two groups. CONCLUSION: Compared to VA-ECMO alone, the combined use of VA-ECMO and IABP is beneficial regarding 30-day survival in selected patients with postcardiotomy shock; successful ECMO weaning and freedom from renal replacement therapy is more common in patients supported with VA-ECMO plus IABP.

Left Ventricular Assist Device Implantation in a Patient with Ventricular Pseudoaneurysm.

Background Left ventricular assist device (LVAD) implantation after contained LV rupture (pseudoaneurysm) represents a difficult surgical problem. Case Description We describe the surgical approach for such a patient. The sewing ring was implanted utilizing a Dacron patch for reconstruction of the free wall, fibrotic LV wall remnants, and a Teflon strip giving additional support for cannula position and hemostasis. The patient had an uneventful recovery and is well 19 months after the procedure. Conclusion LV pseudoaneurysm is not a contraindication for permanent LVAD implantation.

Decellularized Pulmonary Xenograft Matrix PplusN versus Cryopreserved Homograft for RVOT Reconstruction during Ross Procedure in Adults.

BACKGROUND: Decellularized pulmonary homografts are being increasingly adopted for right ventricular outflow tract reconstruction in adult patients undergoing the Ross procedure. Few reports presented Matrix PplusN xenograft (Matrix) in a negative light. The objective of this study was to compare our midterm outcomes of Matrix xenograft versus standard cryopreserved pulmonary homograft (CPHG). METHODS: Eighteen patients received Matrix xenograft between January 2012 and June 2016, whereas 66 patients received CPHG. Using nonparametric statistical tests and survival analysis, we compared midterm echocardiographic and clinical outcomes between the groups. RESULTS: Except for significant age difference (the Matrix group was significantly older with 57 ± 8 years than the CPHG group, 48 ± 9 years, p = 0.02), the groups were similar in all other baseline characteristics. There were no significant differences in cardiopulmonary bypass times (208.3 ± 32.1 vs. 202.8 ± 34.8) or in cross-clamp times (174 ± 33.9 vs. 184.4 ± 31.1) for Matrix and CPHG, respectively. The Matrix group had significantly inferior freedom from reintervention than the CPHG group with 77.8 versus 98.5% (p = 0.02). Freedom from pulmonary valve regurgitation ≥ 2 was not significantly different between the groups with 82.4 versus 90.5% for Matrix versus CPHG, respectively. After median follow-up of 4.9 years, Matrix xenograft developed significantly higher peak pressure gradients compared with CPHG (20.4 ± 15.5 vs. 12.2 ± 9.0 mm Hg; p = 0.04). CONCLUSION: After 5 years of clinical and echocardiographic follow-up, the decellularized Matrix xenograft had inferior freedom from reintervention compared with the standard CPHG. Closer follow-up is necessary to avoid progression of valve failure into right ventricular deterioration.

Fibrin Sealant Patch for the Management of Intractable Bleeding From an LVAD Apex Cannula.

BACKGROUND: Intractable bleeding from the apical cannulation site of a left ventricular assist device (LVAD) is a dreaded complication. CASE REPORT: A 52-year-old male suffering from dilative cardiomyopathy (DCM) with fixed pulmonary hypertension underwent reoperative LVAD implantation after previous mitral valve surgery. The patient underwent three rethoracotomies for bleeding from the apex cannulation site without achieving hemostasis. Conventional techniques and application of fibrin sealants and polymeric sealing devices did not fix the problem. The bleeding stopped after application of the EVARREST® Fibrin Sealant Patch (FSP), and he needed no further transfusions. CONCLUSION: This patch might become a useful tool for intractable bleeding problems in LVAD surgery.

Central Versus Peripheral Arterial Cannulation for Veno-Arterial Extracorporeal Membrane Oxygenation in Post-Cardiotomy Patients.

Different arterial cannulation strategies are feasible for veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in postcardiotomy shock. We aimed to analyze potential benefits and safety of different arterial cannulation strategies. We identified 158 patients with postcardiotomy cardiogenic shock requiring VA-ECMO between 01/10 and 01/19. Eighty-eight patients were cannulated via axillary or femoral artery (group P), and 70 centrally via the ascending aorta directly or through an 8 mm vascular graft anastomosed to the ascending aorta (group C). Demographics and operative parameters were similar. Change of cannulation site for Harlequin's syndrome or hyperperfusion of an extremity occurred in 13 patients in group P but never in group C (p = 0.001). Surgical revision of cannulation site was also encountered more often in group P than C. The need for left ventricular (LV) unloading was similar between groups, whereas surgical venting was more often implemented in group C (11.4% vs. 2.3, p = 0.023). Stroke rates, renal failure, and peripheral ischemia were similar. Weaning rate from ECMO (52.9% vs. 52.3%, p = NS) was similar. The 30 day mortality was higher in group P (60% vs. 76.1%, p = 0.029). Central cannulation for VA-ECMO provides antegrade flow without Harlequin's syndrome, changes of arterial cannula site, and better 30 day survival. Complication rates regarding need for reexploration and transfusion requirements were similar.

First clinical experience with the novel cold storage SherpaPak™ system for donor heart transportation.

BACKGROUND: The current gold standard for donor heart preservation is a three-bag-technique and storage in a cooler filled with slush ice. This technique can cause freezing injury with protein denaturation. We report our early experience with a single-use disposable device (SherpaPak™, Paragonix Technologies, MA, USA) specifically designed for sterile permanent temperature-controlled transportation of donor hearts. METHODS: In this case control study with 2:1 matching we identified 21 patients after heart transplantation depending on type of organ transport (standard three-bag-technique vs. SherpaPak™). The outcome after donor heart storage in the SherpaPak™ was compared with donor heart transportation with the standard technique. RESULTS: Since July 2018 seven patients (5 males; mean age 50.3±13.2years) underwent heart transplantation with the SherpaPak™ system. Cold ischemic time was longer in the SherpaPak™ group (207.7±23.3 vs. 181.6±21.9, P=0.027). SherpaPak™ kept the organ temperature at 5.1±0.8 °C, with an average outside temperature of 21.4±3.6 °C. Among all 21 transplanted patients four developed fatal early graft failure (28.6% vs. 21.4%, P=0.432). Over the first hours we noticed no difference in hemodynamic parameters, CK-MB levels or vasoactive-inotropic score. During first follow-up we noticed slightly better right heart function in the SherpaPak™ group (TAPSE 17.83±2.71 vs. 14.52±2.61 mm, P=0.020). We identified no positive blood cultures in the SherpaPak™ group within the first 30 days after heart transplantation. CONCLUSIONS: The SherpaPak™ provides a constant temperature during transportation with permanent monitoring, never dropping below 4 °C. Organs transported with this novel device showed a normal perioperative function.

Anatomically specific reactive oxygen species production participates in Marfan syndrome aneurysm formation.

Marfan syndrome (MFS) is a connective tissue disorder that results in aortic root aneurysm formation. Reactive oxygen species (ROS) seem to play a role in aortic wall remodelling in MFS, although the mechanism remains unknown. MFS Fbn1C1039G/+ mouse root/ascending (AS) and descending (DES) aortic samples were examined using DHE staining, lucigenin-enhanced chemiluminescence (LGCL), Verhoeff's elastin-Van Gieson staining (elastin breakdown) and in situ zymography for protease activity. Fbn1C1039G/+ AS- or DES-derived smooth muscle cells (SMC) were treated with anti-TGF-ß antibody, angiotensin II (AngII), anti-TGF-ß antibody + AngII, or isotype control. ROS were detected during early aneurysm formation in the Fbn1C1039G/+ AS aorta, but absent in normal-sized DES aorta. Fbn1C1039G/+ mice treated with the unspecific NADPH oxidase inhibitor, apocynin reduced AS aneurysm formation, with attenuated elastin fragmentation. In situ zymography revealed apocynin treatment decreased protease activity. In vitro SMC studies showed Fbn1C1039G/+ -derived AS SMC had increased NADPH activity compared to DES-derived SMC. AS SMC NADPH activity increased with AngII treatment and appeared TGF-ß dependent. In conclusion, ROS play a role in MFS aneurysm development and correspond anatomically with aneurysmal aortic segments. ROS inhibition via apocynin treatment attenuates MFS aneurysm progression. AngII enhances ROS production in MFS AS SMCs and is likely TGF-ß dependent.

Statins Reduce Thoracic Aortic Aneurysm Growth in Marfan Syndrome Mice via Inhibition of the Ras-Induced ERK (Extracellular Signal-Regulated Kinase) Signaling Pathway.

Background Statins reduce aneurysm growth in mouse models of Marfan syndrome, although the mechanism is unknown. In addition to reducing cholesterol, statins block farnesylation and geranylgeranylation, which participate in membrane-bound G-protein signaling, including Ras. We dissected the prenylation pathway to define the effect of statins on aneurysm reduction. Methods and Results Fbn1C1039G/+ mice were treated with (1) pravastatin (HMG-CoA [3-hydroxy-3-methylglutaryl coenzyme A] reductase inhibitor), (2) manumycin A ( MA ; FPT inhibitor), (3) perillyl alcohol ( GGPT 1 and -2 inhibitor), or (4) vehicle control from age 4 to 8 weeks and euthanized at 12 weeks. Histological characterization was performed. Protein analysis was completed on aortic specimens to measure ERK (extracellular signal-regulated kinase) signaling. In vitro Fbn1C1039G/+ aortic smooth muscle cells were utilized to measure Ras-dependent ERK signaling and MMP (matrix metalloproteinase) activity. Pravastatin and MA significantly reduced aneurysm growth compared with vehicle control (n=8 per group). In contrast, PA did not significantly decrease aneurysm size. Histology illustrated reduced elastin breakdown in MA -treated mice compared with vehicle control (n=5 per group). Although elevated in control Marfan mice, both phosphorylated c-Raf and phosphorylated ERK 1/2 were significantly reduced in MA -treated mice (4-5 per group). In vitro smooth muscle cell studies confirmed phosphorylated cR af and phosphorylated ERK 1/2 signaling was elevated in Fbn1C1039G/+ smooth muscle cells (n=5 per group). Fbn1C1039G/+ smooth muscle cell Ras-dependent ERK signaling and MMP activity were reduced following MA treatment (n=5 per group). Corroborating in vitro findings, MMP activity was also decreased in pravastatin-treated mice. Conclusions Aneurysm reduction in Fbn1C1039G/+ mice following pravastatin and MA treatment was associated with a decrease in Ras-dependent ERK signaling. MMP activity can be reduced by diminishing Ras signaling.

Long-term miR-29b suppression reduces aneurysm formation in a Marfan mouse model.

Aortic root aneurysm formation and subsequent dissection and/or rupture remain the leading cause of death in patients with Marfan syndrome. Our laboratory has reported that miR-29b participates in aortic root/ascending aorta extracellular matrix remodeling during early aneurysm formation in Fbn1C1039G/+ Marfan mice. Herein, we sought to determine whether miR-29b suppression can reduce aneurysm formation long-term. Fbn1C1039G/+ Marfan mice were treated with retro-orbital LNA-anti-miR-29b inhibitor or scrambled-control-miR before aneurysms develop either (1) a single dose prenatally (pregnant Fbn1C1039G/+ mice at 14.5 days post-coitum) (n = 8-10, each group) or (2) postnatally every other week, from 2 to 22 weeks of age, and sacrificed at 24 weeks (n = 8-10, each group). To determine if miR-29b blockade was beneficial even after aneurysms develop, a third group of animals were treated every other week, starting at 8 weeks of age, until sacrificed (n = 4-6, each group). miR-29b inhibition resulted in aneurysm reduction, increased elastogenesis, decreased matrix metalloproteinase activity and decreased elastin breakdown. Prenatal LNA-anti-miR-29b inhibitor treatment decreased aneurysm formation up to age 32 weeks, whereas postnatal treatment was effective up to 16 weeks. miR-29b blockade did not slow aortic growth once aneurysms already developed. Systemic miR-29b inhibition significantly reduces aneurysm development long-term in a Marfan mouse model. Drug administration during aortic wall embryologic development appears fundamental. miR-29b suppression could be a potential therapeutic target for reducing aneurysm formation in Marfan syndrome patients.

Risk factors for mortality after pericardiectomy for chronic constrictive pericarditis in a large single-centre cohort.

OBJECTIVES: Constrictive pericarditis (CP) is an uncommon disease with multiple causes and unclear clinical outcomes. To date, few publications have clearly defined risk factors of poor outcomes after surgery for CP. We performed a retrospective analysis of almost 100 patients undergoing surgical treatment for CP at a single institution in order to identify risk factors for perioperative and long-term mortality. METHODS: A total of 97 consecutive patients (67.0% male) undergoing surgery for CP at our institution from 1995 to 2012 were included in the study. CP was diagnosed either preoperatively by cardiac catheterization and appropriate imaging or during surgery. Preoperative and intraoperative risk factors for 30-day and late mortality were analysed using stepwise multivariate logistic and Cox regression analyses. Median follow-up was 1.23 ± 3.96 years (mean 3.08 ± 3.96 years). RESULTS: The mean patient age was 60.0 ± 12.5 years and the underlying aetiology was idiopathic (50.5%), prior cardiac surgery (15.5%), prior mediastinal radiation (9.3%), and miscellaneous (24.7%). All patients underwent either radical (55.2%) or partial (44.8%) pericardiectomy. Concomitant procedures were performed in 54 (55.7%) patients. The total procedure time was 197.0 ± 105.0 min. Cardiopulmonary bypass (CPB) was used in 62 patients with a corresponding CPB time of 124.8 ± 68.4 min. In those patients who underwent CPB, cardioplegic arrest was performed in 53.2% of patients with a mean cross-clamp time of 74.9 ± 41.9 min. Overall 30-day, 1-year and 5-year survival rates were 81.4, 66.5 and 51.6%, respectively, without significant differences according to the underlying aetiology. Multivariate analysis revealed patients with reduced left ventricular ejection fraction (LVEF) [P = 0.01, odds ratio (OR) 3.6] and preoperative right ventricular dilatation (P = 0.04, OR 3.5) to be at significant risk of early mortality. Long-term mortality was independently predicted by the presence of coronary artery disease (CAD) [P < 0.001, hazard ratio (HR) 6.44], chronic obstructive pulmonary disease (P = 0.001, HR 4.21) and preoperative renal insufficiency (P = 0.012, HR 1.8). Concomitant tricuspid valve repair (TVR) appeared to provide protective effect on the long-term survival (P = 0.07). CONCLUSIONS: Surgery for CP is associated with a significant risk based on the poor preoperative patient status. Whenever justified, partial over radical pericardiectomy should be preferred and TVR should be indicated liberally. Reduced LVEF and right ventricular dilatation were independent predictors for early mortality, whereas CAD, chronic obstructive pulmonary disease and renal insufficiency were risk factors for late mortality. Thus, an optimal timing for surgery on CP remains crucial to avoid secondary morbidity with an even worse natural prognosis.

Transcription Factor Runx2 Promotes Aortic Fibrosis and Stiffness in Type 2 Diabetes Mellitus.

RATIONALE: Accelerated arterial stiffening is a major complication of diabetes mellitus with no specific therapy available to date. OBJECTIVE: The present study investigates the role of the osteogenic transcription factor runt-related transcription factor 2 (Runx2) as a potential mediator and therapeutic target of aortic fibrosis and aortic stiffening in diabetes mellitus. METHODS AND RESULTS: Using a murine model of type 2 diabetes mellitus (db/db mice), we identify progressive structural aortic stiffening that precedes the onset of arterial hypertension. At the same time, Runx2 is aberrantly upregulated in the medial layer of db/db aortae, as well as in thoracic aortic samples from patients with type 2 diabetes mellitus. Vascular smooth muscle cell-specific overexpression of Runx2 in transgenic mice increases expression of its target genes, Col1a1 and Col1a2, leading to medial fibrosis and aortic stiffening. Interestingly, increased Runx2 expression per se is not sufficient to induce aortic calcification. Using in vivo and in vitro approaches, we further demonstrate that expression of Runx2 in diabetes mellitus is regulated via a redox-sensitive pathway that involves a direct interaction of NF-κB with the Runx2 promoter. CONCLUSIONS: In conclusion, this study highlights Runx2 as a previously unrecognized inducer of vascular fibrosis in the setting of diabetes mellitus, promoting arterial stiffness irrespective of calcification.

Enhanced caspase activity contributes to aortic wall remodeling and early aneurysm development in a murine model of Marfan syndrome.

OBJECTIVE: Rupture and dissection of aortic root aneurysms remain the leading causes of death in patients with the Marfan syndrome, a hereditary connective tissue disorder that affects 1 in 5000 individuals worldwide. In the present study, we use a Marfan mouse model (Fbn1(C1039G/+)) to investigate the biological importance of apoptosis during aneurysm development in Marfan syndrome. APPROACH AND RESULTS: Using in vivo single-photon emission computed tomographic-imaging and ex vivo autoradiography for Tc99m-annexin, we discovered increased apoptosis in the Fbn1(C1039G/+) ascending aorta during early aneurysm development peaking at 4 weeks. Immunofluorescence colocalization studies identified smooth muscle cells (SMCs) as the apoptotic cell population. As biological proof of concept that early aortic wall apoptosis plays a role in aneurysm development in Marfan syndrome, Fbn1(C1039G/+) mice were treated daily from 2 to 6 weeks with either (1) a pan-caspase inhibitor, Q-VD-OPh (20 mg/kg), or (2) vehicle control intraperitoneally. Q-VD-OPh treatment led to a significant reduction in aneurysm size and decreased extracellular matrix degradation in the aortic wall compared with control mice. In vitro studies using Fbn1(C1039G/+) ascending SMCs showed that apoptotic SMCs have increased elastolytic potential compared with viable cells, mostly because of caspase activity. Moreover, in vitro (1) cell membrane isolation, (2) immunofluorescence staining, and (3) scanning electron microscopy studies illustrate that caspases are expressed on the exterior cell surface of apoptotic SMCs. CONCLUSIONS: Caspase inhibition attenuates aneurysm development in an Fbn1(C1039G/+) Marfan mouse model. Mechanistically, during apoptosis, caspases are expressed on the cell surface of SMCs and likely contribute to elastin degradation and aneurysm development in Marfan syndrome.

Not all porcelain is the same: classification of circular aortic calcifications (porcelain aorta) according to the impact on therapeutic approach.

Severe aortic calcification, also known as "porcelain aorta," has a major impact on patient outcome. Its presence also influences the choice of procedure depending on where it is located. However, to date there is no clear definition on how this term should be employed, being often used as an exclusion criteria for conventional surgery where aortic clamping and/or cannulation is required.We here suggest a classification of the "porcelain aorta" regarding its location and how it influences particular therapeutic options. Therefore, making more clear what procedures would represent an increased risk for the patient and which are more suitable when discussed in a "Heart Team."Type I implies localization of a circumferential calcification in the ascending aorta. Type IA represents the calcified aorta with no possibility of clamping and Type IB represents the calcified aorta with possible clamping. Type II addresses the calcification of the descending aorta including or not the aortic arch.