Enhanced Cardiac S100A1 Expression Improves Recovery from Global Ischemia-Reperfusion Injury.

Gene-targeted therapy with the inotropic Ca2 + -sensor protein S100A1 rescues contractile function in post-ischemic heart failure and is being developed towards clinical trials. Its proven beneficial effect on cardiac metabolism and mitochondrial function suggests a cardioprotective effect of S100A1 in myocardial ischemia-reperfusion injury (IRI). Fivefold cardiomyocyte-specific S100A1 overexpressing, isolated rat hearts perfused in working mode were subjected to 28 min ischemia (37 °C) followed by 60 min reperfusion. S100A1 overexpressing hearts showed superior hemodynamic recover: Left ventricular pressure recovered to 57 ± 7.3% of baseline compared to 51 ± 4.6% in control (p = 0.025), this effect mirrored in LV work and dP/dt(max). Troponin T and lactate dehydrogenase was decreased in the S100A1 group, as well as FoxO pro-apoptotic transcription factor, indicating less tissue necrosis, whereas phosphocreatine content was higher after reperfusion. This is the first report of a cardioprotective effect of S100A1 overexpression in a global IRI model.

Aorta Related and All-cause Mortality in Patients with Aortic Intramural Haematoma.

OBJECTIVES: The prognosis of patients with intramural haematoma (IMH) of the aorta beyond the first year after diagnosis remains largely unknown. In particular, patients that do not undergo interventions are lost to follow-up. The aim was to assess medium-term outcome in IMH patients. METHODS: Post hoc analysis of 63 consecutive patients presenting with IMH between 1999 and 2013 was performed. Patients meeting imaging criteria at the first presentation were included even if follow-up imaging showed evidence of intimal disruption or false lumen flow. RESULTS: Eighteen patients presented with type A and 45 with type B IMH (29% vs. 71%, p < .001). The mean age was 71 ± 9.2 years, range 42-88 years. Follow-up was completed in 97% of patients by May 2017 and represents a mean follow-up of 6.3 ± 3.6 years. Freedom from intervention in patients with type B IMH was 40%. TEVAR was performed in 47% because of development, unmasking of an entry tear (57%), progression to acute type B dissection (24%), or subsequent dilation of the affected aortic segments (19%). Open repair was performed in 13% of type B IMH patients because of dilation of the descending aorta. In type A IMH, 89% underwent open repair. Aorta related 30 day, 6 month, 1 year, and late mortality were 1.6%, 6.3%, 6.3%, and 9.5%, respectively, for all IMH patients. All-cause 30 day, 6 month, 1 year, and late mortality were 1.6%, 6.3%, 6.3%, and 47.6%, respectively, for all IMH patients. Late mortality in type B IMH did not differ whether patients underwent TEVAR, open repair, or received best medical treatment only (26% vs. 22%, p = 1.0). CONCLUSIONS: Late aorta related mortality in IMH was low whereas all-cause mortality was substantial. Aorta related mortality in IMH patients only occurs during the first year after diagnosis. Interventions after the first year are rarely necessary.

Mechanical versus biological aortic valve replacement strategies.

Aortic valve replacement (AVR) is the most frequently performed procedure in valve surgery. The controversy about the optimal choice of the prosthetic valve is as old as the technique itself. Currently there is no perfect valve substitute available. The main challenge is to choose between mechanical and biological prosthetic valves. Biological valves include pericardial (bovine, porcine or equine) and native porcine bioprostheses designed in stented, stentless and sutureless versions. Homografts and pulmonary autografts are reserved for special indications and will not be discussed in detail in this review. We will focus on the decision making between artificial biological and mechanical prostheses, respectively. The first part of this article reviews guideline recommendations concerning the choice of aortic prostheses in different clinical situations while the second part is focused on novel strategies in the treatment of patients with aortic valve pathology.

Hemodynamic performance of Edwards Intuity valve in a compliant aortic root model.

Numerous designs of bioprosthetic valves exist. The sutureless surgical valve is a newer design concept which combines elements of the transcatheter valve technology with surgical valves. This design aims at shorter and easier implantation. It was the aim of this study to perform hemodynamic and kinematic measurements for this type of valves to serve as a baseline for following studies which investigate the effect of the aortic root on the valve performance. To this end, the Edwards Intuity aortic valve was investigated in a new in vitro flow loop mimicking the left heart. The valve was implanted in a transparent, compliant aortic root model, and the valve kinematics was investigated using a high speed camera together with synchronized hemodynamic measurements of pressures and flows. The valve closure was asynchronous (one by one leaflet), and the valve started to close before the deceleration of the fluid. The aortic root model showed a dilation of the sinuses which was different to the ascending aorta, and the annulus was found to move towards the left ventricle during diastole and towards the aorta during systole.

Plasma-functionalized electrospun matrix for biograft development and cardiac function stabilization.

Cardiac tissue engineering approaches can deliver large numbers of cells to the damaged myocardium and have thus increasingly been considered as a possible curative treatment to counteract the high prevalence of progressive heart failure after myocardial infarction (MI). Optimal scaffold architecture and mechanical and chemical properties, as well as immune- and bio-compatibility, need to be addressed. We demonstrated that radio-frequency plasma surface functionalized electrospun poly(ɛ-caprolactone) (PCL) fibres provide a suitable matrix for bone-marrow-derived mesenchymal stem cell (MSC) cardiac implantation. Using a rat model of chronic MI, we showed that MSC-seeded plasma-coated PCL grafts stabilized cardiac function and attenuated dilatation. Significant relative decreases of 13% of the ejection fraction (EF) and 15% of the fractional shortening (FS) were observed in sham treated animals; respective decreases of 20% and 25% were measured 4 weeks after acellular patch implantation, whereas a steadied function was observed 4 weeks after MSC-patch implantation (relative decreases of 6% for both EF and FS).

Management of aortic aneurysms in patients with connective tissue disease.

Acute dissection and rupture of aortic aneurysms comprise for 1-2% of all deaths in developed countries. Dilation of the aorta is caused by several different mechanisms including inherited disorders of connective tissue. Recent reports estimate that 20% of patients presenting with thoracic aortic disease do have an underlying genetic basis of disease.

Acute aortic dissection type A.

BACKGROUND: Acute aortic dissection type A (AADA) is a life-threatening vascular emergency. Clinical presentation ranges from pain related to the acute event, collapse due to aortic rupture or pericardial tamponade, or manifestations of organ or limb ischaemia. The purpose of this review was to clarify important clinical issues of AADA management, with a focus on diagnostic and therapeutic challenges. METHODS: Based on a MEDLINE search the latest literature on this topic was reviewed. Results from the German Registry for Acute Aortic Dissection Type A (GERAADA) are also described. RESULTS: Currently, the perioperative mortality rate of AADA is below 20 per cent, the rate of definitive postoperative neurological impairment approaches 12 per cent and the long-term prognosis after surviving the acute phase of the disease is good. Many pathology- and therapy-associated factors influence the outcome of AADA, including prompt diagnosis with computed tomography and better cerebral protection strategies during aortic arch reconstruction. Endovascular technologies are emerging that may lead to less invasive treatment options. CONCLUSION: AADA is an emergency that can present with a wide variety of clinical scenarios. Advances in the surgical management of this complex disease are improving outcomes.

Fine-tuning of substrate architecture and surface chemistry promotes muscle tissue development.

Tissue engineering has been increasingly brought to the scientific spotlight in response to the tremendous demand for regeneration, restoration or substitution of skeletal or cardiac muscle after traumatic injury, tumour ablation or myocardial infarction. In vitro generation of a highly organized and contractile muscle tissue, however, crucially depends on an appropriate design of the cell culture substrate. The present work evaluated the impact of substrate properties, in particular morphology, chemical surface composition and mechanical properties, on muscle cell fate. To this end, aligned and randomly oriented micron (3.3±0.8 µm) or nano (237±98 nm) scaled fibrous poly(ε-caprolactone) non-wovens were processed by electrospinning. A nanometer-thick oxygen functional hydrocarbon coating was deposited by a radio frequency plasma process. C2C12 muscle cells were grown on pure and as-functionalized substrates and analysed for viability, proliferation, spatial orientation, differentiation and contractility. Cell orientation has been shown to depend strongly on substrate architecture, being most pronounced on micron-scaled parallel-oriented fibres. Oxygen functional hydrocarbons, representing stable, non-immunogenic surface groups, were identified as strong triggers for myotube differentiation. Accordingly, the highest myotube density (28±15% of total substrate area), sarcomeric striation and contractility were found on plasma-coated substrates. The current study highlights the manifold material characteristics to be addressed during the substrate design process and provides insight into processes to improve bio-interfaces.

Efficacy and safety of sirolimus and everolimus in heart transplant patients: a retrospective analysis.

BACKGROUND: Since its introduction as an immunosuppressant in the late 1990s, sirolimus (SRL) has been used to prevent rejections after heart transplantation (HTx) in the United States. An analogue, everolimus (ERL) has been mainly used in Europe. We performed a retrospective longitudinal single-center study to evaluate efficacy and side effects of SRL and ERL. PATIENTS AND METHODS: We analyzed 71 patients, 39 in the SRL and 32 in the ERL group. The following data were collected: Trough levels of SRL and ERL, biopsy-proven rejections, renal function, blood lipids, hematology, blood pressure, pulse rate, and side effects (via an anonymous questionnaire). Follow-up time was 6 months. No prisoners or organs from prisoners were used in the study. RESULTS: Introduction of SRL or ERL into therapy took place 44 or 42 months (average) after HTx. SRL and ERL were equally effective in preventing rejection (8/39 versus 6/32). Hemoglobin levels decreased slightly in the SRL group (nonsignificant). Leucocytes and thrombocyte levels decreased in both groups (P < .05 only in the ERL group). Creatinine levels remained unchanged. Cholesterol and triglyceride levels increased significantly in the SRL group. High-density lipoprotein levels increased significantly in the ERL group. Vital signs remained stable in both groups. Side effects (mainly edema, gastrointestinal symptoms and infections) were considerable and prompted discontinuation in 39% of all patients in both groups. Infections were more frequent in SRL (18/39 versus 12/32, nonsignificant). Calcineurin therapy could be reduced by 25% in SRL and 45% in ERL. CONCLUSION: The impact of SRL and ERL on laboratory values and rejection rates, as well as on clinical parameters, is similar with a slight advantage to ERL regarding lipids and rate of infections (not significant). Both SRL and ERL allow an important reduction of calcineurin-therapy; however, both drugs have considerable side effects, which often require discontinuation of therapy.

Prevention of rupture of abdominal aortic aneurysm.

BACKGROUND AND AIMS: Two thirds of patients with an abdominal aortic aneurysm (AAA) have relevant coronary artery disease (CAD). AAAs are prevalent in up to 16% of smokers with CAD. General screening of AAA is controversial. Aim was to assess the potential of finding AAA prior to rupture among patients with known CAD. Main endpoint was whether AAA could have been found during follow-up by sonography or at other time of cardiovascular evaluation. MATERIAL AND METHODS: Retrospective study. 213 consecutive, formerly unknown emergently operated AAAs, treated emergently for symptoms (n = 91) or rupture (n = 122) (rAAA) between January 1998 and June 2005. Patient charts were analysed and primary care physicians contacted. RESULTS: At presentation, mean age was 71 (+/-9) years, twenty (9%) were female. AAA had a mean diameter of 7.6 cm. Two thirds (143) were clinically obese (BMI 27 +/-5). 137 (64%) were active smokers, 32 (15%) had diabetes, 151 (71%) were hypertensive, and 80 (38%) received statin treatment. CAD had been diagnosed in 95 (45%) 9 years earlier and followed up. Thirty-five (16%) had had myocardial infarction. Echocardiography had been performed in 52 (24%). Thirty day mortality after open surgery was 25 (21%). CONCLUSION: All patients with rAAA had been seen by a GP or cardiologist within a year prior to presentation. The cost effectiveness of selective AAA screening should be evaluated in a larger study.

Quality of life after acute type B dissection in the era of thoracic endovascular aortic repair.

BACKGROUND: Conservative management of acute type B aortic dissection is currently being challenged by primary thoracic endovascular aortic repair. Aim was to assess outcome and quality of life after these different approaches using an adjusted standard population as benchmark. PATIENTS AND METHODS: Observational study of a prospectively collected (January 2000 to December 2005) consecutive series of 87 patients with acute type B aortic dissection. Patients were 63 +/- 13 years old and 68 were men (78.2 %). Seventy-two were managed conservatively (83 %) and 15 invasively (12 by endovascular aortic repair). Follow-up was 36 +/- 19 months. Endpoints were early and late morbidity and mortality, and long-term quality of life as assessed by the Short Form health survey questionnaire. RESULTS: Patient cohorts were similar regarding age, risk profile and local disease. In the conservative cohort, four patients died during early (5.6 %) and eight during long-term follow-up (cumulative four years survival rate 79 %). Thirty-two patients needed secondary surgical management (44 %), i.e. delayed aortic repair (n = 11), or interventions on adjacent aortic sections or major branches (n = 21). In the surgical cohort no patient died, and no repeated interventions were necessary after the peri-operative period. Long-term quality of life scores were 100 (69-115) in conservatively and 94 (75-124) in invasively managed patients. Normal scores range from 85 to 115. CONCLUSIONS: Primary endovascular management of uncomplicated acute type B dissection is safe and leads to excellent long-term results, whereas secondary interventions were required with high incidence after initial conservative management. Long-term quality of life, however, returned to normal with any successful treatment strategy.

Connexin 43 expression in human hypertrophied heart due to pressure and volume overload.

Left ventricular hypertrophy (LVH) is due to pressure overload or mechanical stretch and is thought to be associated with remodeling of gap-junctions. We investigated whether the expression of connexin 43 (Cx43) is altered in humans in response to different degrees of LVH. The expression of Cx43 was analyzed by quantitative polymerase chain reaction, Western blot analysis and immunohistochemistry on left ventricular biopsies from patients undergoing aortic or mitral valve replacement. Three groups were analyzed: patients with aortic stenosis with severe LVH (n=9) versus only mild LVH (n=7), and patients with LVH caused by mitral regurgitation (n=5). Cx43 mRNA expression and protein expression were similar in the three groups studied. Furthermore, immunohistochemistry revealed no change in Cx43 distribution. We can conclude that when compared with mild LVH or with LVH due to volume overload, severe LVH due to chronic pressure overload is not accompanied by detectable changes of Cx43 expression or spatial distribution.

[Does yoghurt gnaw at cardiac valves?]. / Nagt Joghurt an den Herzklappen?

A 22-year-old man with pre-existing aortic valve disease contracted acute lactobacillus endocarditis six weeks after a dental procedure despite adequate prophylaxis. We discuss the limitations of prophylaxis for infective endocarditis in use until the end of 2008 and describe the new updated guidelines. We also explain the treatment of lactobacillus endocarditis and speculate on possible health risks of the increasing use of lactobacillus-containing dairy products, especially in immune-compromised patients.

Diastolic dysfunction of the cardiac allograft and maximal exercise capacity.

BACKGROUND: Peak oxygen uptake (peak Vo(2)) is an established integrative measurement of maximal exercise capacity in cardiovascular disease. After heart transplantation (HTx) peak Vo(2) remains reduced despite normal systolic left ventricular function, which highlights the relevance of diastolic function. In this study we aim to characterize the predictive significance of cardiac allograft diastolic function for peak Vo(2). METHODS: Peak Vo(2) was measured using a ramp protocol on a bicycle ergometer. Left ventricular (LV) diastolic function was assessed with tissue Doppler imaging sizing the velocity of the early (Ea) and late (Aa) apical movement of the mitral annulus, and conventional Doppler measuring early (E) and late (A) diastolic transmitral flow propagation. Correlation coefficients were calculated and linear regression models fitted. RESULTS: The post-transplant time interval of the 39 HTxs ranged from 0.4 to 20.1 years. The mean age of the recipients was 55 +/- 14 years and body mass index (BMI) was 25.4 +/- 3.9 kg/m(2). Mean LV ejection fraction was 62 +/- 4%, mean LV mass index 108 +/- 22 g/m(2) and mean peak Vo(2) 20.1 +/- 6.3 ml/kg/min. Peak Vo(2) was reduced in patients with more severe diastolic dysfunction (pseudonormal or restrictive transmitral inflow pattern), or when E/Ea was > or =10. Peak Vo(2) correlated with recipient age (r = -0.643, p < 0.001), peak heart rate (r = 0.616, p < 0.001) and BMI (r = -0.417, p = 0.008). Of all echocardiographic measurements, Ea (r = 0.561, p < 0.001) and Ea/Aa (r = 0.495, p = 0.002) correlated best. Multivariate analysis identified age, heart rate, BMI and Ea/Aa as independent predictors of peak Vo(2). CONCLUSIONS: Diastolic dysfunction is relevant for the limitation of maximal exercise capacity after HTx.

Generalized dilating diathesis in patients with popliteal arterial aneurysm.

BACKGROUND: Aim of this study was to analyse the relationship between popliteal artery aneurysm (PAA) and generalized arteriomegaly. PATIENTS AND METHODS: In this consecutive serie, thirty-three patients (1 woman, mean age 69.7 +/- 9.6 years) undergoing PAA repair between 1996 and 2000 agreed to participate in a duplex screening program to assess the diameters of the infrarenal abdominal aorta, common and external iliac, common and superficial femoral and contralateral popliteal arteries as well as common carotid and brachial arteries. RESULTS: The prevalence of arteriomegaly and aneurysmal disease, respectively, was as follows: abdominal aorta 15/33 (45.5%) and 8/33 (24.2%), common iliac artery 34/66 (51.5%) and 23/66 (34.8%), common femoral artery 55/66 (83.3%) and 7/66 (10.6%) as well as contralateral popliteal artery 7/33 (21.2%) 15/33 (45.5%). Significantly larger carotid artery diameters were found comparing PAA patients with age- and body surface adjusted healthy controls (p < 0.001). Furthermore, patients with multiple peripheral arterial aneurysms had significantly larger diameters of the brachial (p < 0.02) and external iliac (p < 0.005). CONCLUSIONS: Our findings support the hypothesis of a diathesis for a generalized arteriomegaly with a predilection for further aneurysms of the abdominal aorta, iliac arteries, femoral and contralateral popliteal arteries in patients with PAA.

[Ascending aortic and pulmonary trunk aneurysms]. / Aneurysmata der Aorta ascendens und des Truncus pulmonalis.

A case of two non-atherosclerotic aneurysms localised in the ascending aorta and in the pulmonary trunk is presented. Histopathologically, a severe granulomatous inflammation affecting the whole aneurysms wall was documented. To the best of our knowledge it is the second ever documented case of simultaneous occurrence of aneurysms in the aorta and the pulmonary artery.

ECG-triggered muscular counterpulsation for treatment of low cardiac output.

BACKGROUND: Skeletal muscular counterpulsation (MCP) has been used as a new noninvasive technique for treatment of low cardiac output. The MCP method is based on ECG-triggered skeletal muscle stimulation. The purpose of the present study was to evaluate acute hemodynamic changes induced by MCP in the experimental animal. METHODS: Eight anaesthetized pigs (43+/-4 kg) were studied at rest and after IV â-blockade (10 mg propranolol) before and after MCP. Muscular counterpulsation was performed on both thighs using trains (75 ms duration) of multiple biphasic electrical impulses with a width of 1 ms and a frequency of 200 Hz at low (10 V) and high (30 V) amplitude. ECG-triggering was used to synchronize stimulation to a given time point. LV pressure-volume relations were determined using the conductance catheter. After baseline measurements, MCP was carried out for 10 minutes at low and high stimulation amplitude. The optimal time point for MCP was determined from LV pressure-volume loops using different stimulation time points during systole and diastole. Best results were observed during end-systole and, therefore, this time point was used for stimulation. RESULTS: Under control conditions, MCP was associated with a significant decrease in pulmonary vascular resistance (-18%), a decrease in systemic vascular resistance (-11%) and stroke work index (-4%), whereas cardiac index (+2%) and ejection fraction (+6%) increased slightly. Pressure-volume loops showed a leftward shift with a decrease in end-systolic volume. After â-blockade, cardiac function decreased (HR, MAP, EF, dP/dt max), but it improved with skeletal muscle stimulation (HR +10% and CI +17%, EF +5%). There was a significant decrease in pulmonary (-19%) and systemic vascular resistance (-29%). CONCLUSIONS: In the animal model, ECG-triggered skeletal muscular counterpulsation is associated with a significant improvement in cardiac function at baseline and after IV â-blockade. Thus, MCP represents a new, non-invasive technique which improves cardiac function by diastolic compression of the peripheral arteries and veins, with a decrease in systemic vascular resistance and increase in cardiac output.