Ascending aortic and proximal hemiarch replacement with antegrade cerebral perfusion for a penetrating aortic ulcer.

We report the surgical repair of a penetrating aortic ulcer in the distal ascending aorta close to the brachiocephalic trunk, by supracoronary ascending aortic and hemiarch replacement via a full sternotomy. The procedure is performed under moderate hypothermia with bilateral antegrade cerebral perfusion.

A case report of recurrent acute myocardial infarction and cardiac arrest due to aortic dissection secondary to IgG4-related aortitis.

Occlusion of the right coronary artery is a relatively rare complication of type A aortic dissection and an example of type 2 myocardial infarction (MI) as well but when it occurs, it may have a fatal result for the patient. Aortic pseudoaneurysms are local type A dissections with a restricted extent in which the majority of the aortic wall has been breached and luminal blood is held in only by a thin rim of the remaining wall, mainly purely the adventitia. They typically occur from iatrogenic trauma by interventional procedures or previous cardiac surgery. We present a case of a 56 years old patient who suffered an acute functional MI due to such pseudoaneurysm formed in the context of an undiagnosed aortitis. The etiology remained unclear until the surgical aortic prosthesis was deemed necessary, finding chronic IgG4 infiltrates in the aortic tissue. To our knowledge, this is the first case of IgG4-related aortitis causing functional MI and cardiogenic shock.

Taking the frozen elephant trunk technique to the next level by a stented side branch for a left subclavian artery connection: a feasibility study.

OBJECTIVES: Our goal was to develop a modified frozen elephant trunk (FET) prosthesis with a stented left subclavian artery (LSA) side branch for LSA connection and to perform preclinical testing in a human cadaver model. METHODS: We measured aortic diameters, distance between and diameters of supra-aortic vessels and the distance from the LSA offspring to the level of the left vertebral artery offspring in 70 patients. Based on these measurements, a novel FET prosthesis was developed (Cryolife/Jotec, Hechingen, Germany) featuring a stented side branch for an intrathoracic LSA connection. The feasibility and ease of implantation were tested in 2 human cadaver models at the Anatomical Institute of the Medical University Graz. A covered stent graft (Advanta V12™ by Atrium Medical Corp., Hudson, NH, USA) was used for an LSA extension. RESULTS: Accurate deployment of the novel FET prosthesis with anatomical orientation of the stented side branch towards the LSA ostium followed by consecutive stent graft deployment was feasible in both cases. Proximalizing the distal anastomosis level from zone 3 to zone 1 not only diminished the complexity of the procedure but substantially facilitated the completion of the distal anastomosis. A 2.5-cm long extension stent graft was sufficient to seal to the LSA and to maintain left vertebral artery patency in both cases. CONCLUSIONS: This initial study in human anatomical bodies could demonstrate the feasibility of implanting a newly designed FET prosthesis. This evolution of the FET technique has the potential to substantially ease total aortic arch replacement by proximalization of the distal anastomosis into zone 1 and by shortening spinal and lower body hypothermic circulatory arrest times via a stented side branch to the LSA. This direct connection enables early restoration of systemic perfusion.

The Anti-Cancer Multikinase Inhibitor Sorafenib Impairs Cardiac Contractility by Reducing Phospholamban Phosphorylation and Sarcoplasmic Calcium Transients.

Tyrosine-kinase inhibitors (TKIs) have revolutionized cancer therapy in recent years. Although more targeted than conventional chemotherapy, TKIs exhibit substantial cardiotoxicity, often manifesting as hypertension or heart failure. Here, we assessed myocyte intrinsic cardiotoxic effects of the TKI sorafenib and investigated underlying alterations of myocyte calcium homeostasis. We found that sorafenib reversibly decreased developed force in auxotonically contracting human myocardia (3 µM: -25 ± 4%, 10 µM: -29 ± 7%, 30 µM: -43 ± 12%, p < 0.01), reduced peak cytosolic calcium concentrations in isolated cardiomyocytes (10 µM: 52 ± 8.1% of baseline, p < 0.001), and slowed cytosolic calcium removal kinetics (RT50, RT10, Tau, p < 0.05). Beta-adrenergic stimulation induced augmentation of calcium transient (CaT) amplitude was attenuated in sorafenib-treated cells (2.7 ± 0.3-fold vs. 3.6 ± 0.2-fold in controls, p < 0.001). Sarcoplasmic reticulum (SR) calcium content was reduced to 67 ± 4% (p < 0.01), and SR calcium re-uptake slowed (p < 0.05). Sorafenib significantly reduced serine 16 phosphorylation of phospholamban (PLN, p < 0.05), while PLN threonine 17 and CaMKII (T286) phosphorylation were not altered. Our data demonstrate that sorafenib acutely impairs cardiac contractility by reducing S16 PLN phosphorylation, leading to reduced SR calcium content, CaT amplitude, and slowed cytosolic calcium removal. These results indicate myocyte intrinsic cardiotoxicity irrespective of effects on the vasculature and chronic cardiac remodeling.

Atrial fibrillation in transcatheter aortic valve implantation patients: Incidence, outcome and predictors of new onset.

BACKGROUND: There is controversial evidence if atrial fibrillation (AF) alters outcome after transcatheter aortic valve implantation (TAVI). TAVI itself may promote new-onset AF (NOAF). METHODS: We performed a single-center study including 398 consecutive patients undergoing TAVI. Before TAVI, patients were divided into a sinus rhythm (SR) group (n=226, 57%) and baseline AF group (n=172, 43%) according to clinical records and electrocardiograms. Furthermore, incidence and predictors of NOAF were recorded. RESULTS: Baseline AF patients had a significantly higher 1-year mortality than the baseline SR group (19.8% vs. 11.5%, p=0.02). NOAF occurred in 7.1% of patients with prior SR. Previous valve surgery was the only significant predictor of NOAF (HR 5.86 [1.04-32.94], p<0.05). NOAF was associated with higher rehospitalization rate (62.5 vs. 34.8%, p=0.04), whereas mortality was unaffected. CONCLUSIONS: This study shows that NOAF is associated with higher rates of rehospitalization but not mortality after TAVI. Overall, patients with pre-existing AF have higher mortality.

Re-sternotomy as an unwelcome side-effect of unknown effervescent tablet intake?

Four hours after surgery for aortic valve stenosis and tricuspid valve regurgitation, an unknown foreign body was present on the routine chest X-ray. We performed re-sternotomy in order to retrieve this foreign body. The foreign body was easy to move on fluoroscopy but we could not extract it. We concluded that the foreign body was in a subdiaphragmatic location. As a consequence, we performed gastroscopy. A white, frothy mass (similar to an undissolved effervescent tablet) within an ulcerated lesion was seen and partially extracted.

Accurate preoperative echocardiography has more impact on prediction of long-term mortality than intra-operatively measured flow in coronary bypass grafts.

OBJECTIVE: Our study aimed to analyze the predictive value of intra-operative bypass graft flow measurements for long-term mortality. METHODS: A total of 1593 consecutive coronary artery bypass graft (CABG) patients routinely underwent intra-operative bypass graft flow measurements with the transit-time flow meter (TTFM: Cardiomed(®)). The results of the flow measurements and the demographics were analyzed retrospectively. RESULTS: The mean follow-up was 3.8 years (0.5-8.8 years) with no losses to follow-up. Overall mortality was 10.1%. The preoperative left ventricular ejection fraction (LVEF) (echocardiograph) was the highest independent predictor of long-term survival (hazard ratio 0.97, p = 0.004) in all groups. The univariate analysis for the CABG I group showed that besides LVEF, female gender (hazard ratio 3.6, p = 0.02) was also significant. For the CABG II group, additive EuroSCORE (European System for Cardiac Operative Risk) (ES) (hazard ratio 1.4, p = 0.0001) and age (hazard ratio 1.1, p = 0.001) were significant. In the CABG III group, ES (hazard ratio 1.2, p < 0.0001), age (hazard ratio 1.04, p = 0.001), IMA (hazard ratio 0.5, p < 0.0001) and concomitant aortic valve replacement (AVR) (hazard ratio 2.1, p = 0.03) were significant, in addition to the LVEF. CONCLUSION: With quality-controlled surgeons checked by intra-operative TTFM, accurate quantification of preoperative LVEF significantly predicts long-term outcome. Effective bypass graft flows failed to predict outcome in CABG patients, regardless of the degree of coronary artery disease (CAD) and concomitant AVR.

cAMP- and Ca²(+) /calmodulin-dependent protein kinases mediate inotropic, lusitropic and arrhythmogenic effects of urocortin 2 in mouse ventricular myocytes.

BACKGROUND AND PURPOSE: Urocortin 2 is beneficial in heart failure, but the underlying cellular mechanisms are not completely understood. Here we have characterized the functional effects of urocortin 2 on mouse cardiomyocytes and elucidated the underlying signalling pathways and mechanisms. EXPERIMENTAL APPROACH: Mouse ventricular myocytes were field-stimulated at 0.5 Hz at room temperature. Fractional shortening and [Ca²(+)](i) transients were measured by an edge detection and epifluorescence system respectively. Western blots were carried out on myocyte extracts with antibodies against total phospholamban (PLN) and PLN phosphorylated at serine-16. KEY RESULTS: Urocortin 2 elicited time- and concentration-dependent positive inotropic and lusitropic effects (EC50 : 19 nM) that were abolished by antisauvagine-30 (10 nM, n= 6), a specific antagonist of corticotrophin releasing factor (CRF) CRF2 receptors. Urocortin 2 (100 nM) increased the amplitude and decreased the time constant of decay of the underlying [Ca²(+)](i) transients. Urocortin 2 also increased PLN phosphorylation at serine-16. H89 (2 µM) or KT5720 (1 µM), two inhibitors of protein kinase A (PKA), as well as KN93 (1 µM), an inhibitor of Ca²(+)/calmodulin-dependent protein kinase II (CaMKII), suppressed the urocortin 2 effects on shortening and [Ca²(+)](i) transients. In addition, urocortin 2 also elicited arrhythmogenic events consisting of extra cell shortenings and extra [Ca²(+)](i) increases in diastole. Urocortin 2-induced arrhythmogenic events were significantly reduced in cells pretreated with KT5720 or KN93. CONCLUSIONS AND IMPLICATIONS: Urocortin 2 enhanced contractility in mouse ventricular myocytes via activation of CRF2 receptors in a cAMP/PKA- and Ca²(+)/CaMKII-dependent manner. This enhancement was accompanied by Ca²(+)-dependent arrhythmogenic effects mediated by PKA and CaMKII.

Glucose-transporter-mediated positive inotropic effects in human myocardium of diabetic and nondiabetic patients.

Insulin causes inotropic effects via Ca(2+)-dependent and Ca(2+)-independent pathways. The latter one is potentially glucose dependent. We examined inotropic responses and signal transduction of insulin in human atrial myocardium of diabetic and nondiabetic patients to test for the role of glucose transporters. Experiments were performed in isolated atrial myocardium of 88 patients undergoing cardiac surgery and 28 ventricular muscle samples of explanted hearts. Influence of insulin (0.02 micromol/L) on isometric twitch force was examined with and without blocking glucose transporter (GLUT) 4 translocation (latrunculin), sodium-coupled glucose transporter (SGLT) 1 (phlorizin, T-1095A), or PI3-kinase (wortmannin). Experiments were performed in Tyrode solution containing glucose or pyruvate as energetic substrate. Messenger RNA expression of glucose transporters (GLUT1, GLUT4, SGLT1, SGLT2) was analyzed in atrial and ventricular myocardium of both diabetic and nondiabetic patients. Developed force increases after insulin (to 117.8% +/- 2.4% and 115.8% +/- 1.9%) in trabeculae from patients with and without diabetes. Inotropic effect was reduced after displacing glucose with pyruvate as well as after PI3-kinase inhibition (to 103% +/- 2%) or inhibition of glucose transporters GLUT4 (to 105% +/- 2%) and SGLT1 (phlorizin to 106% +/- 2%, T-1095A to 105% +/- 2%), without differences between the 2 groups. In glucose-free pyruvate-containing solution, only inhibition of PI3-kinase but not blocking glucose transporters resulted in further inhibitory effects. Messenger RNA expression did not show significant differences between patients with or without diabetes. Insulin exerts positive inotropic effects in human atrial myocardium. These effects are mediated via a PI3-kinase-sensitive and a glucose-transport-sensitive pathway. Differences in functional effects or messenger RNA expression of glucose transporters were not detectable between patients with and without diabetes.

Identification of a rare subset of adipose tissue-resident progenitor cells, which express CD133 and TRPC3 as a VEGF-regulated Ca2+ entry channel.

VEGF-induced Ca2+ signalling was investigated in CD133+/VEGFR-2+ progenitor cells isolated from human adipose stroma. Colonies derived from CD133+ immunoselected cells displayed inhomogenous Ca2+ signals, with variable magnitude of VEGF-induced Ca2+ entry, which positively correlated with expression of the Ca2+ channel protein TRPC3. High levels of VEGF-induced Ca2+ entry and TRPC3 expression were preferentially detected in rim areas of expanding colonies. Dominant negative suppression of TRPC3 inhibited VEGF-induced Ca2+ entry into CD133+ cells. Our results identify TRPC3 as a key Ca2+ entry channel in a subset of CD133+ stem cells. We suggest TRPC3 as an essential determinant of cell fate in CD133+ progenitor-derived colonies.

Forty-one-month follow-up of the Symmetry aortic connector system for proximal venous anastomosis.

OBJECTIVE: Results of short- and midterm follow-up studies of the patency rate of the Symmetry aortic connector systems (St Jude Medical, Inc, Minneapolis, Minn) are controversial. Long-term follow-up studies are still lacking (so far, the longest mean follow-up period was 19 months). The aim of our study was (1) to evaluate the patency rate of this device over a longer time-period and (2) to analyze risk factors for graft occlusion. METHODS: Between November 2000 and July 2003, 76 Symmetry aortic connector systems were implanted in 42 patients. At follow-up, 24 patients with 44 mechanical connectors were studied with 64-slice cardiac computed tomography. Eight patients had died previously, 6 patients refused to undergo a computed tomographic scan, and 4 patients had to be excluded because of impaired renal function. RESULTS: From a total of 44 mechanical connectors studied, 24 (55%) were occluded, 20 (45%; confidence intervals 31%-61%) were patent, and 7 of these grafts showed stenosis in the area of the connector. Mean follow-up was 41 +/- 10 months (18-52 months). Sex, age, left main stenosis, hyperlipidemia, hypertension, renal failure, target vessel, stenosis of the target vessel, diameter of the target vessel, type of surgical intervention, diabetes, ejection fraction, postoperative anticoagulation regimen, and the connector size showed no significant influence on the bypass graft patency (P > .05). The bypass graft flow was recognized to be the only risk factor for bypass graft occlusion (P = .0256). CONCLUSION: Midterm follow-up data show a high number of occluded Symmetry aortic connector system vein grafts. On the basis of these observations, the use of the connector was abandoned at our institution.

Influence of a tilting prosthetic mitral valve orientation on the left ventricular flow - an experimental in vivo magnetic resonance imaging study.

OBJECTIVE: Orientation-related monoleaflet mechanical valve flow and velocity studies in the downstream are limited in mitral valve replacement studies. METHODS: In five sheep, ventricular blood flow was visualized prior to the implantation of a Medtronic Hall tilting valve model. In six sheep, the implant orientation was either anatomical (disc aligned with the anterior leaflet) or anti-anatomical. The mitral subvalvular apparatus was preserved. Sheep were positioned within an 1.5 T field strength MR scanner (Magnetom Sonata; Siemens) to assess time-dependent three dimensional blood flow. RESULTS: The preoperative ventricular velocity profiles presented negligible individual variances. Streamlines passed homogeneously without any spatial differences in flow velocities into the left ventricle. Starting from the anatomical position, blood entered mainly through the major orifice of the mechanical valve. The single artificial leaflet mimicked the rudder effect of the natural anterior mitral leaflet, preventing blood streaming directly towards the septum. The area with inhomogeneous blood velocities in the ventricle increased but not significantly from the preoperative status. The non-axial inflow not directed directly to the apex converted to a similar helix as observed in the preoperative cases. Anti-anatomical orientation of the prosthesis caused a significant increase in turbulence immediately after passing the mitral prosthesis. The main stream was changed so significantly that the blood flow shifted towards the septum and caused higher velocities of the stream profiles and turbulence apically. CONCLUSIONS: To achieve optimal hemodynamics, orientation of the mitral tilting valve has to be considered carefully, as has been long known from aortic valve replacement studies.

Superior left atrial approach to the mitral valve: incidence of postoperative arrhythmia.

BACKGROUND AND AIM OF THE STUDY: The superior left atrial approach to mitral surgery involves exposure of the mitral valve through a longitudinal, craniocaudally orientated incision in the roof of the left atrium. The study aim was to evaluate the incidence of postoperative arrhythmias following this procedure. METHODS: Fifty-nine patients underwent either mitral valve repair (n = 20), mitral valve replacement (n = 26) or an associated procedure (n = 13), including aortic valve replacement, coronary artery bypass grafting and atrial septal defect closure. Eight patients had undergone previous surgery on the mitral valve. Patients were classified according to their preoperative rhythm: sinus rhythm (SR), paroxysmal or chronic atrial fibrillation (AF), or permanent pacing. Changes in cardiac rhythm were evaluated postoperatively, after four weeks, and at late follow up (mean 23.8 months). RESULTS: Preoperatively, 24 patients had shown SR, 10 had paroxysmal AF, 24 had chronic AF, and one patient had permanent pacing. At the time of discharge, SR was recorded in 18 patients who had SR preoperatively, in seven who had paroxysmal AF preoperatively, and in one patient who had chronic AF preoperatively. At follow up, SR was seen in 19 patients with preoperative SR, in seven with paroxysmal AF preoperatively, and in two with chronic AF preoperatively. Four patients received permanent pacemakers postoperatively due to total heart block or bradycardia. CONCLUSION: The superior left atrial approach to mitral valve surgery appears to be safe as it maintains the sinus rhythm in a high proportion of patients postoperatively. In addition, it is not normally prone to technical complications.

If in left human atrium: a potential contributor to atrial ectopy.

OBJECTIVE: The left human atrium plays an important role in initiation of atrial fibrillation (AF) and the hyperpolarization activated cation current (I(f)) is a candidate for contributing to abnormal automaticity. However, electrophysiological data concerning I(f) are not available in this cardiac region and we therefore investigated I(f) in human left atrial tissue. METHODS: Human atrial myocytes were isolated from the left atrial appendage (LAA) and the left atrial wall (LAW) obtained from patients undergoing open heart surgery. I(f) was measured with the whole-cell patch-clamp technique. RESULTS: I(f) densities between -70 and -110 mV were found to be significantly higher in LAA than in LAW cells. Furthermore, in the group of LAA cells the half maximal activation potential (V(1/2)) was found to be less negative (V(1/2) of -84.3+/-1.9 mV, n=14/9) compared to LAW cells (V(1/2) of -97.8+/-2.1 mV, n=28/9). Beta-adrenergic receptor stimulation with isoproterenol (1 microM) caused an acceleration of current activation and a V(1/2) shift to more positive potentials in cells of both regions (LAA: 8.8+/-2.3 mV, n=6/4 and LAW: 8.9+/-2.6 mV, n=6/4). Simulations using a mathematical model of the human atrial myocyte demonstrated that I(f) was able to induce spontaneous activity in the model at a regular rhythm due to the interplay of I(f), Na(+)/Ca(2+) exchange current and Ca(2+) release of the sarcoplasmic reticulum (SR). CONCLUSIONS: Our study revealed the presence of I(f) in left atrial myocytes and showed that I(f) parameters depend on atrial region. I(f) current densities were sufficient to convert the mathematical model of a quiescent human atrial cell into a "pacemaker cell". These data support the hypothesis of I(f) as a contributor to abnormal automaticity in human atrial tissue.

Severe heart laceration in penetrating chest trauma: thoracoscopy as a key to diagnosis.

A patient had attempted suicide by firing a butcher's gun into his left chest 3 cm caudal to the mammilla. Transthoracic echocardiography and CT-scan showed a discrete hematopneumothorax but no pericardial effusion, the cardio respiratory condition was stable. As the bolt had been aimed directly at the heart of the patient, thoracoscopy was performed to rule out cardiac trauma. Thoracoscopy showed a distinct severe contusion of the otherwise intact pericardium and a hemopericardium. Immediate thoracotomy and pericardiotomy revealed significant intrapericardial bleeding caused by an incomplete rupture of the left ventricle. The condition was successfully treated by direct reinforced suture.