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OBJECTIVES Coronary artery bypass grafting or supra-arterial myotomy is now suggested as a better therapeutic option in myocardial bridging (MB) when medical treatment fails to control symptoms. For left anterior descending (LAD) MB, minimally invasive coronary artery bypass via a lower ministernotomy can be offered. METHODS Forty-four consecutive patients who underwent elective minimally invasive coronary artery bypass surgery from 2005 to 2014 via an inferior sternotomy using the left internal mammary artery as a bypass graft for LAD MB were evaluated retrospectively. RESULTS The mean age was 59.1 ± 13.1 years with 26 (59%) men and 18 (41%) women. The mean body mass index was 27.2 ± 3.9 and the mean EuroSCORE II was 1.6 ± 1.8. Routine coronary multislice computed tomography angiography on the 6th postoperative day revealed 97.7% graft patency. During the initial hospital stay, 1 patient (2.3%) underwent a reoperation for early graft failure. Forty patients (91%) could be followed up for a mean period of 64.4 ± 24.5 months after the procedure, during which 2 patients (4.5%) died of non-cardiac causes and 9 patients (20.5%) underwent postoperative coronary angiography with confirmed graft occlusion in only 1 case (2.3%). The improvement in the distribution of patients in the Canadian Cardiovascular Society class 0 was from 4 patients (9%) preoperatively to 37 patients (84%) at the end of the follow-up period (P-value 0.001). CONCLUSIONS Minimally invasive coronary artery bypass surgery via a lower ministernotomy may be safe and efficient for treating LAD artery MB with acceptable complication rates, cosmetic benefits and patency rates.

Background: Diabetic vasculopathy plays an important role in the pathophysiology of coronary artery disease (CAD) with oxidative stress as a strong mediator. This study aims to elucidate the underlying pathomechanisms of diabetic cardiac vasculopathy leading to coronary disease with an emphasis on the role of oxidative stress. Therefore, novel insights into antioxidant pathways might contribute to new strategies in the treatment and prevention of diabetic CAD. Methods: In 20 patients with insulin-dependent or non-insulin dependent diabetes mellitus (IDDM/NIDDM) and 39 non-diabetic (CTR) patients, myocardial markers of oxidative stress, vasoactive proteins, endothelial nitric oxide synthase (eNOS), activated phosphorylated eNOS (p-eNOS), and antioxidant enzymes, e.g., tetrahydrobiopterin generating dihydrofolate reductase (DHFR), heme oxygenase (HO-1), as well as serum markers of inflammation, e.g., E-selectin, interleukin-6 (IL-6), and lipid metabolism, e.g., high- and low-density lipoptrotein (HDL- and LDL-cholesterol) were determined in specimens of right atrial tissue and in blood samples from type 2 diabetic and non-diabetic patients undergoing coronary artery bypass graft (CABG) surgery. Results: IDDM/NIDDM increased markers of inflammation (e.g., E-selectin, p = 0.005 and IL-6, p = 0.051), decreased the phosphorylated myocardial p-eNOS (p = 0.032), upregulated the myocardial stress response protein HO-1 (p = 0.018), and enhanced the serum LDL-/HDL-cholesterol ratio (p = 0.019). However, the oxidative stress markers in the myocardium and the expression of vasoactive proteins (eNOS, DHFR) showed only marginal adverse changes in patients with IDDM/NIDDM. Conclusion: Dyslipidemia and myocardial inflammation seem to be the major determinants of diabetic CAD complications. Dysregulation in pro-oxidative enzymes might be attributable to the severity of CAD and oxidative stress levels in all included patients undergoing CABG.

To analyze whether cardiac surgical residents can perform their first surgeries without compromising patients' safety or outcomes, by comparing their performance and results to those of senior surgeons. All documented CABGs conducted between 2002 and 2020 were included. Surgeries were divided according to the experience level of the main surgeon (defined by the number of CABG conducted by him/her) using the following thresholds: 1000; 150; 80 and 35. This resulted in 5 groups: senior surgeons (the reference group); attending surgeons; fellow surgeons; advanced residents and new residents. Primary endpoint was 30 day mortality. Secondary endpoints included a list of intra and post-operative parameters (including in-hospital complications). A multivariable analysis was conducted. 16,486 CABG were conducted by 66 different surgeons over a period of 18 years. Multivariable analysis did not find significant differences between both the primary and the secondary endpoints. Skin-to-skin time correlated significantly with experience level, as new residents needed almost 30% more time than senior surgeons (234 vs 180 minutes). With a suitable supervision by experienced surgeons, patient selection and sufficient resources (longer duration of surgery), surgical residents can perform CABGs with good results and without compromising the patient's outcome.

ObjectivesAcute pulmonary embolism can be a life-threatening condition with a high mortality. The treatment choice is a matter of debate. The early and late outcomes of patients treated with surgical pulmonary embolectomy for acute pulmonary embolism in a single center were analyzed.MethodsAll consecutive patients operated on for pulmonary embolism between January 2002 and March 2017 were reviewed. Patient demographics and pre- and postoperative clinical data were retrieved from our patient registry, and risk factors for in-hospital and long-term mortality were identified.ResultsIn total, 175 patients (mean age 59±3 years, 50% male) were operated on for acute pulmonary embolism. In-hospital mortality was 19% (34/175). No differences were found when comparing surgery utilizing a beating heart or cardioplegic arrest. Risk factors for in-hospital mortality were age >70 years [odds ratio (OR) 4.8, confidence interval (CI) 1.7–13.1, p=0.002], body surface area 2 (OR 4.7, CI 1.6–13.7, p=0.004), preoperative resuscitation (OR 14.1, CI 4.9–40.8, pConclusionSurgical pulmonary embolectomy as a therapy for acute pulmonary embolism demonstrates excellent short- and long-term results in patients with an otherwise life-threatening disease, especially in younger patients with a body surface area >2 m2 and pulmonary embolism caused by deep vein thrombosis. Pulmonary embolectomy should therefore not be reserved as a treatment of last resort for clinically desperate circumstances.

Background Brain‐derived neurotrophic factor (BDNF) is expressed in neuronal and nonneuronal cells and may affect vascular functions via its receptor, tropomyosin‐related kinase B (TrkB). In this study, we determined the expression of BDNF in different perivascular adipose tissue (PVAT) depots of patients with established coronary atherosclerosis. Methods and Results Serum, vascular tissue, and PVAT surrounding the proximal aorta (C‐PVAT) or internal mammary artery (IMA‐PVAT) was obtained from 24 patients (79% men; mean age, 71.7±9.7 years; median body mass index, 27.4±4.8 kg/m 2 ) with coronary atherosclerosis undergoing elective coronary artery bypass surgery. BDNF protein levels were significantly higher in C‐PVAT compared with IMA‐PVAT, independent of obesity, metabolic syndrome, or systemic biomarkers of inflammation. mRNA transcripts of TrkB, the BDNF receptor, were significantly reduced in aorta compared with IMA. Vessel wall TrkB immunosignals colocalized with cells expressing smooth muscle cell markers, and confocal microscopy and flow cytometry confirmed BDNF receptor expression in human aortic smooth muscle cells. Significantly elevated levels of protein tyrosine phosphatase 1B, a negative regulator of TrkB signaling in the brain, were also observed in C‐PVAT. In vitro, inhibition of protein tyrosine phosphatase 1B blunted the effects of BDNF on smooth muscle cell proliferation, migration, differentiation, and collagen production, possibly by upregulation of low‐affinity p75 neurotrophin receptors. Expression of nerve growth factor or its receptor tropomyosin‐related kinase A did not differ between C‐PVAT and IMA‐PVAT. Conclusions Elevated expression of BDNF in parallel with local upregulation of negative regulators of neurotrophin signaling in perivascular fat and lower TrkB expression suggest that vascular BDNF signaling is reduced or lost in patients with coronary atherosclerosis.

Background. Obesity is related to coronary artery disease (CAD) and worse outcomes in coronary artery bypass graft (CABG) patients. Adipose tissue itself is an endocrine organ that secretes many humoral mediators, such as adipokines, which can induce or reduce inflammation and oxidative stress. Objectives. We investigate the relationship between the body mass index (BMI), inflammation, and oxidative stress by measuring serum levels of leptin, interleukin-6, and 3-nitrotyrosine in CABG patients and correlate their levels to the cardiovascular and operative risk profiles. Methods and Results. 45 men (2, who were diagnosed with CAD and scheduled for elective CABG, were included after applying the following exclusion criteria: prior myocardial infarction, reoperation, female gender, and smoking. Patients’ blood samples were taken preoperatively. Several markers were measured. We found significant correlations between leptin and BMI p<0.0001 as well as between leptin and 3-nitrotyrosine p=0.006. Interleukin-6 was correlated with C-reactive protein p<0.0001 and with the incidence of insulin-dependent diabetes mellitus p=0.036, arterial hypertension p=0.044, reduced left ventricular function p=0.003, and severe coronary calcification p=0.015. It was also associated with significantly longer extracorporeal bypass time p=0.009. Postoperative deep sternal wound infections could be predicted by a higher BMI p=0.003 and leptin level p=0.001. Conclusions. There seems to be a correlation between inflammatory processes and cardiovascular morbidity in our cohort. Further, the incidence of deep sternal wound infections is related to a higher BMI and leptin serum level.

Members of the genus Bartonella are fastidious Gram-negative facultative intracellular bacteria that are typically transmitted by arthropod vectors. Several Bartonella spp. have been found to cause culture-negative endocarditis in humans. Here, we report the case of a 75-year old German woman with prosthetic valve endocarditis due to Bartonella washoensis. The infecting agent was characterized by sequencing of six housekeeping genes (16S rRNA, ftsZ, gltA, groEL, ribC, rpoB) applying a multilocus sequence typing (MLST) approach. The 5097 bp of the concatenated housekeeping gene sequence from the patient were 99.0% identical to a B. washoensis strain from a red squirrel (Sciurus vulgaris orientis) from China. 39% (24/62) of red squirrel (S. vulgaris) samples from the Netherlands were positive for the B. washoensis gltA gene variant detected in the patient. This suggests that the red squirrel is the reservoir host for human infection in Europe.

Cardiovascular risk factors may act by modulating the composition and function of the adventitia. Here we examine how age affects perivascular adipose tissue (PVAT) and its paracrine activities during neointima formation. Aortic tissue and PVAT or primary aortic smooth muscle cells from male C57BL/6JRj mice aged 52 weeks (&ldquo, middle-aged&rdquo, ) were compared to tissue or cells from mice aged 16 weeks (&ldquo, adult&rdquo, ). Vascular injury was induced at the carotid artery using 10% ferric chloride. Carotid arteries from the middle-aged mice exhibited smooth muscle de-differentiation and elevated senescence marker expression, and vascular injury further aggravated media and adventitia thickening. Perivascular transplantation of PVAT had no effect on these parameters, but age-independently reduced neointima formation and lumen stenosis. Quantitative PCR analysis revealed a blunted increase in senescence-associated proinflammatory changes in perivascular tissue compared to visceral adipose tissue and higher expression of mediators attenuating neointima formation. Elevated levels of protein inhibitor of activated STAT1 (PIAS1) and lower expression of STAT1- or NF&kappa, B-regulated genes involved in adipocyte differentiation, inflammation, and apoptosis/senescence were present in mouse PVAT, whereas PIAS1 was reduced in the PVAT of patients with atherosclerotic vessel disease. Our findings suggest that age affects adipose tissue and its paracrine vascular activities in a depot-specific manner. PIAS1 may mediate the age-independent vasculoprotective effects of perivascular fat.

The Ram cichlid Mikrogeophagus ramirezi (Myers & Harry, 1948) was used to examine whether flash photography can be a stressor for fish in aquaria. The point in time of the highest cortisol concentration in whole‐body homogenates was determined by the temporal course of the cortisol response following air exposure as stressor. Thus, the potential stress response to camera flashlight was examined 22 min after exposure to a single flash and after repeated flashes by applying 10 flashes per minute for 8 hr/day over 2 weeks. In both experiments the stress parameters cortisol and glucose were not increased due to exposure to the flash light. In contrast, after a single flash mean cortisol values tended to be lower and mean glucose values were significantly lower than in the control group, and after repeated flashes mean cortisol and glucose values were significantly lower than in the control group. Furthermore, treated fish showed less intraspecific aggressive interactions. These results can be explained by a possible dazzling or irritation of the fish by camera flashes, thus reducing the natural aggressive behaviour and, consequently, the concentration of stress hormones and mobilisation of glucose. In summary, the physiological stress parameters cortisol and glucose do not reveal that flash photography induces stress in M. ramirezi, and, on the contrary, might even reduce stress effects by lowering intraspecific aggressive behaviour of the fish.

Background Our study aimed to evaluate changes in the contractile behavior of human myocardium after exposure to caffeine and taurine, the main active ingredients of energy drinks (EDs), and to evaluate whether taurine exhibits any inotropic effect at all in the dosages commonly used in EDs. Methods Myocardial tissue was removed from the right atrial appendages of patients undergoing cardiac surgery and prepared to obtain specimens measuring 4 mm in length. A total of 92 specimens were exposed to electrical impulses at a frequency of 75 bpm for at least 40 min to elicit their maximum contractile force before measuring the isometric contractile force (ICF) and duration of contraction (CD). Following this, each specimen was treated with either taurine (group 1, n = 29), or caffeine (group 2, n = 31) or both (group 3, n = 32). After exposure, ICF and CD measuring were repeated. Post-treatment values were compared with pre-treatments values and indicated as percentages. Results Exposure to taurine did not alter the contraction behavior of the specimens. Exposure to caffeine, in contrast, led to a significant increase in ICF (118 ± 03%, p

Background. Lactococcus garvieae (LG) is a gram-positive coccus known to be a major pathogen in aqua farming, which is responsible for severe outbreaks. Its incidence in humans is extremely rare. Prior to 1985, all bacteria in the genus Lactococcus were included in the Streptococcus genus. The first human infection was documented in 1991, and since then, the relevance and clinical significance in humans has increased. Case Description. We present the clinical course of an LG endocarditis in a 78-year-old man who had a history of exertional dyspnea. The patient’s blood tests showed increased inflammation values, and a transesophageal ultrasound (TEE) showed a stenosis of the prosthetic aortic valve. Blood cultures were positive for LG, leading to a diagnosis of infective endocarditis. After 6 weeks of intravenous antibiotics and a prosthetic aortic valve replacement, the patient made a good recovery. Review of the Literature. After the first documented case in 1991 to 2018, 25 cases of LG endocarditis have been described in PubMed and MEDLINE. We reviewed all reported cases of LG endocarditis, commenting on predisposing risk factors, the course and outcome of the disease. Conclusion. LG endocarditis is a rare disease. Consumption of raw fish, abnormalities of the digestive tract, immune deficiency, and underlying cardiac conditions appear to be risk factors for an infective endocarditis due to LG. Improved determination techniques are likely to lead to a better and faster identification of the bacterium. This identification allows a faster and individualized therapy, which in turn affects the outcome.

Leptin, a hormone produced by adipose tissue, has been linked to many regulatory pathways. Its role in the complex relationship between obesity and CVD is not yet clear. The aim of the present study was to evaluate whether leptin interferes directly with cardiac function regulation, altering its contractile force character, and hence contributing to different pathological processes. Muscle samples were obtained from human atrial myocardium. Each trial included two samples from the same patient. They were simultaneously electrically stimulated under sustained perfusion to perform isometric contractions. One sample was treated with a high concentration of human recombinant leptin (1 µg/ml). The other was treated with placebo and served as a control. The exhibited contraction forces (CF) and the contraction duration (CD) after 20 min of treatment were normalised by dividing them by the values before the treatment and reported as a percentage. A total of ten successful trials were conducted. Exposure to leptin did not yield a statistically significant variation in both CF and CF. In the treatment group, CF% measured 108 (95 % CI 91, 125) % and CD% measured 95 (95 % CI 90, 101) % after 20 min. In the control group, CF% measured 105 (90 % CI 84, 126) % and CD% measured 92 (95 % CI 80, 105) % after 20 min. We concluded that leptin does not alter the contractile character of human atrial tissues, even in supraphysiological dosage. These results suggest that leptin does not play a role in short-term cardiac regulation.

Purpose. Ivabradine has emerged as a new antiarrhythmic agent that could compete with the traditional ones, such as beta-blockers. This experimental study aims to ascertain whether ivabradine directly interferes with the myocardial contractility in an in vitro environment. Methods. Myocardial tissues from the right atrial appendages of patients undergoing cardiac surgery were dissected to obtain 40 specimens from 20 patients (length: 3 mm), which were exposed to electrical impulses at a frequency of 75 bpm for 30 min to reach a steady state. Specimens were then categorised into four groups (each including five patients). The first group was the control, whereas the second, third, and fourth were treated with 60 nM, 200 nM, and 2 μM ivabradine, respectively. We assessed five different contraction parameters before and after a 15 min treatment and calculated their relative changes, which were then compared to the control group. Results. Ivabradine has affected the force of contraction significantly in vitro (p=0.009). However, force of contraction decreased in both the control group (93.5 ± 4.7%) and the second group (94.1 ± 4.5%, p=0.8) and force of contraction remained unchanged in the third group (101.0 ± 4.1%, p=0.24) and increased significantly in the fourth group (108.9 ± 11.6%, p=0.008). There was no change in other contraction parameters, such as passive tension force (97.1 ± 5.1%, p=0.368), duration of contraction (99.1 ± 4.3%, p=0.816), time to peak (96.6 ± 3.0%, p=0.536), and time to relaxation (101.2 ± 7.0%, p=0.564). Conclusions. Ivabradine did not interfere with the contractile behaviour of human atrial tissue when it was used in therapeutic dosages in vitro. However, it increased the contractility slightly, when it was used in supratherapeutic dosage.

Neonatal abstinence syndrome (NAS) is usually treated with opiate derivatives and supported with nonpharmacological treatment. This prospective, randomized, controlled, blinded, single-center study was carried out between March 2009 and November 2014. Newborn infants diagnosed with NAS after maternal opioid substitution therapy were eligible for inclusion. Infants were randomly allocated to the acupuncture group (combining laser acupuncture and pharmacological therapy of morphine and phenobarbital) or control group (pharmacological therapy alone). Laser acupuncture was performed with a LABpen MED 10 (675 nm/10 mW) at 5 ear and 4 body acupuncture points, bilaterally, and sessions were repeated every day. The primary outcome measure was duration of oral morphine therapy for NAS. Secondary outcomes included highest single Finnegan score, time to highest single Finnegan score, maximum amount of oral morphine solution (in milliliters per kilogram and milligrams per kilogram), time to maximum amount of oral morphine solution, and length of hospital stay. Twenty-eight newborns (14 in each group) were eligible for analysis. Duration of oral morphine therapy was significantly reduced in the acupuncture group compared with the control group (28 vs 39 days, respectively, P = .019). In addition, we observed a significantly reduced length of hospital stay in the acupuncture group compared with the control group (35 days [interquartile range 25 to 47] vs 50 days [36 to 66], P = .048). Adjunctive laser acupuncture significantly reduced the duration of morphine therapy in newborns with NAS.

Experimental and human autopsy studies have associated adventitial lymphangiogenesis with atherosclerosis. An analysis of perivascular lymphangiogenesis in patients with coronary artery disease is lacking. Here, we examined lymphangiogenesis and its potential regulators in perivascular adipose tissue (PVAT) surrounding the heart (C-PVAT) and compared it with PVAT of the internal mammary artery (IMA-PVAT). Forty-six patients undergoing coronary artery bypass graft surgery were included. Perioperatively collected C-PVAT and IMA-PVAT were analyzed using histology, immunohistochemistry, real time PCR, and PVAT-conditioned medium using cytokine arrays. C-PVAT exhibited increased PECAM-1 (platelet endothelial cell adhesion molecule 1)-positive vessel density. The number of lymphatic vessels expressing lymphatic vessel endothelial hyaluronan receptor-1 or podoplanin was also elevated in C-PVAT and associated with higher inflammatory cell numbers, increased intercellular adhesion molecule 1 (ICAM1) expression, and fibrosis. Significantly higher expression of regulators of lymphangiogenesis such as vascular endothelial growth factor (VEGF)-C, VEGF-D, and VEGF receptor-3 was observed in C-PVAT compared to IMA-PVAT. Cytokine arrays identified angiopoietin-2 as more highly expressed in C-PVAT vs. IMA-PVAT. Findings were confirmed histologically and at the mRNA level. Stimulation of human lymphatic endothelial cells with recombinant angiopoietin-2 in combination with VEGF-C enhanced sprout formation. Our study shows that PVAT surrounding atherosclerotic arteries exhibits more extensive lymphangiogenesis, inflammation, and fibrosis compared to PVAT surrounding a non-diseased vessel, possibly due to local angiopoietin-2, VEGF-C, and VEGF-D overexpression.

Objectives: To evaluate the significance of a balloon expandable system (INTUITY Elite), we compared open surgical minimally- invasive AVR with conventional bioprosthetic valves and minimally- invasive AVR with rapid deployment system. This study shall investigate new innovations concerning aortic valve replacement. Methods: This retrospective study included all patients (n = 441) that underwent isolated aortic valve replacement from 2012–2014. Several 349 patients received an open surgical, minimally- invasive aortic valve replacement with common bioprosthetic valves. 92 patients were treated with the minimally- invasive aortic valve replacement using a balloon expandable valve (INTUITY elite). Results: Minimally- invasive AVR with the balloon expandable system (INTUITY Elite) showed a statistically significant reduction of bypass- time (9%, p 0.05). The in- hospital mortality seems to be a bit lower in the group of rapid deployment replacement (2.2% versus 4.0%). Compared with TAVI procedures the in-hospital mortality in the group with rapid deployment valve replacement is also lower (2.2% versus 3.6%). Conclusion: The minimally invasive AVR with the balloon expandable system (INTUITY Elite) shows a statistically significant reduction of bypass- time as well as cross-clamp time. Almost each procedure is feasible with minimally- invasive access. We experienced a significant better blood flow as a result of extreme low transvalvular gradients (< 10mmHg) in balloon expandable system (INTUITY Elite). Regarding all aspects the new generation of rapid deployment systems seems to become a severe alternative to bioprosthetic valves.