Hantavirus Cardiopulmonary Syndrome Due to Imported Andes Hantavirus Infection in Switzerland: A Multidisciplinary Challenge, Two Cases and a Literature Review.

Two travellers returning from South America were diagnosed with Andes hantavirus infection, the only member of the Hantaviridae family known to be transmitted from person to person. We describe the clinical course and therapeutic and infection control measures. While both patients showed high viral load (VL) and shedding over several months, 1 patient recovered within 1 week from severe respiratory illness that required noninvasive ventilation, whereas the second patient developed severe hantavirus cardiopulmonary syndrome that required extracorporeal membrane oxygenation for 27 days. The clinical course in the latter patient was complicated by severe disseminated intravascular coagulopathy with diffuse hemorrhage that necessitated mass transfusions, as well as by multiple organ failure, including the need for renal replacement therapy. Results of VL in blood, respiratory secretions, and semen for the first 9 months of follow-up are reported. To our knowledge, these are the first cases of Andes hantavirus infection detected in Europe.

New role of ventricular assist devices as bridge to transplantation: European perspective.

PURPOSE OF REVIEW: Progress of ventricular assist devices (VAD) technology led to improved survival and apparently low morbidity. However, from the European perspective, updated analysis of EUROMACS reveals a somewhat less impressive picture with respect to mortality and morbidity. RECENT FINDINGS: We describe the great demand of cardiac allografts versus the lack of donors, which is larger in Europe than in the United States. Technical progress of VADs made it possible to work out a modern algorithm of bridge-to-transplant, which is tailored to the need of the particular patient. We analyze the burden of patients undergoing bridge-to-transplant therapy. They are condemned to an intermediate step, coupled with additional major surgery and potential adverse events during heart transplantation. SUMMARY: Based on current registry data, we do have to question the increasingly popular opinion, that the concept of heart transplantation is futureless, which seems to be for someone who treats and compares both patients (VAD and heart transplantation) in daily practice, questionable. Up to now, left ventricular assist device therapy remains a bridge to a better future, which means a bridge to technical innovations or to overcome the dramatic lack of donors in Europe.

Long-term follow-up after implantation of the Shelhigh® No-React® complete biological aortic valved conduit.

OBJECTIVES: Long-term follow-up reports after implantation of the Shelhigh® (Shelhigh, Inc., NJ, USA) No-React® aortic valved conduit used for aortic root replacement do not exist. METHODS: Between November 1998 and December 2007, the Shelhigh® No-React® aortic valved conduit was implanted in 291 consecutive patients with a mean age of 69.6 ± 9.1 years, and 33.7% were female (n = 98). Indications were annulo-aortic ectasia (n = 202), aortic valve stenosis combined with ascending aortic aneurysm (n = 67), acute type A aortic dissection (n = 29), endocarditis (n = 26) and other related pathologies (n = 48) including 62 patients with previous cardiac surgery. Data from two cardiac institutions were analysed retrospectively using SPSS (SPSS Software IBM, Inc., 2014, NY, USA). RESULTS: Operative mortality was 10% (n = 29). Main cause of death was cardiac failure in 15 patients (51.8%), neurological events in 6 patients (20.7%), respiratory failure in 4 patients (13.8%), bleeding complications in 2 patients (6.9%) and gastrointestinal ischaemia in 2 cases (6.9%). There were 262 hospital survivors and all were entered in the follow-up study (100% complete). During the long-term follow-up (mean 70.3 ± 53.1 in months), a total of 126/262 patients (44.3%) died. Main causes of death in patients after discharge were cardiac (n = 37, 14.1%), neurological (n = 15, 5.7%) respiratory (n = 12, 4.6%), endocarditis (n = 12, 4.6%) and peripheral vascular disease (n = 5, 1.9%). In 29 (11.1%) patients, the cause of death could not be determined. Reoperation was required in 25 (8.6%) patients due to infection of the conduit (n = 9), aortoventricular disconnection (n = 4), pseudoaneurysm formation (n = 4) and structural valve degeneration (n = 8). Reoperations were performed 5.0 ± 3.8 (range 0.1-11.7) years after index surgery. CONCLUSIONS: The Shelhigh® No-React® aortic valved conduit showed satisfactory short-term operative results. However, the long-term follow-up revealed a relatively high rate of deaths, which may be explained by the epidemiology of the patient group, but a substantial proportion of deaths could not be clarified. The overall rate of reoperation (8.6%) during the mid-term follow-up is worrisome and the failures due to aortoventricular disconnection, endocarditis and pseudoaneurysm formation remain unexplained. The redo-procedures were technically demanding. We recommend close follow-up of patients with the Shelhigh® No-React® aortic valved conduit, because besides classical structural valve degeneration, unexpected findings may be observed.

[Ventricular assist device ­ Possibilities of long-term mechanical circulatory support]. / Herzersatzverfahren - Möglichkeiten der langfristigen mechanischen Kreislaufunterstützung.

In Switzerland 200'000 people suffer from congestive heart failure. Approximately 10'000 patients find themselves in an advanced state of the disease. When conservative treatment options are no longer available heart transplantation is the therapy of choice. Should this not be an option due to long waiting lists or medical issues assist device therapy becomes an option. Assist device therapy is separated in short-term and long-term support. Long-term support is nowadays performed with ventricular assist devices (VADs). The native heart is still in place and supported in parallel to the remaining function of the heart. The majority of patients are treated with a left ventricular assist device (LVAD). The right ventrical alone (RVAD) as well as bi-ventricular support (BiVAD) is rarely needed. The modern VADs are implantable and create a non-pulsative bloodflow. A percutaneous driveline enables energy supply and pump-control. Indication strategies for VAD implantations include bridge to transplant (short term support), bridge to candidacy and bridge to transplant. VADs become more and more a definite therapeutic option (destination therapy). VAD therapy might be a realistic alternative to organ transplantation in the near future.

Rapamycin impairs endothelial cell function in human internal thoracic arteries.

BACKGROUND: Definitive fate of the coronary endothelium after implantation of a drug-eluting stent remains unclear, but evidence has accumulated that treatment with rapamycin-eluting stents impairs endothelial function in human coronary arteries. The aim of our study was to demonstrate this phenomenon on functional, morphological and biochemical level in human internal thoracic arteries (ITA) serving as coronary artery model. METHODS: After exposure to rapamycin for 20 h, functional activity of ITA rings was investigated using the organ bath technique. Morphological analysis was performed by scanning electron microscopy and evaluated by two independent observers in blinded fashion. For measurement of endothelial nitric oxide synthase (eNOS) release, mammalian target of rapamycin (mTOR) and protein kinase B (PKB) (Akt) activation, Western blotting on human mammary epithelial cells-1 and on ITA homogenates was performed. RESULTS: Comparison of the acetylcholine-induced relaxation revealed a significant concentration-dependent decrease to 66 ± 7 % and 36 ± 7 % (mean ± SEM) after 20-h incubation with 1 and 10 µM rapamycin. Electron microscopic evaluation of the endothelial layer showed no differences between controls and samples exposed to 10 µM rapamycin. Western blots after 20-h incubation with rapamycin (10 nM-1 µM) revealed a significant and concentration-dependent reduction of p (Ser 1177)-eNOS (down to 38 ± 8 %) in human mammary epithelial cells (Hmec)-1. Furthermore, 1 µM rapamycin significantly reduced activation of p (Ser2481)-mTOR (58 ± 11 %), p (Ser2481)-mTOR (23 ± 4 %) and p (Ser473)-Akt (38 ± 6 %) in ITA homogenates leaving Akt protein levels unchanged. CONCLUSIONS: The present data suggests that 20-h exposure of ITA rings to rapamycin reduces endothelium-mediated relaxation through down-regulation of Akt-phosphorylation via the mTOR signalling axis within the ITA tissue without injuring the endothelial cell layer.

Mitral valve replacement in patients under 65 years of age: mechanical or biological valves?

PURPOSE OF REVIEW: There is controversy regarding the optimal choice of prosthetic valves in patients less than 65 years of age requiring mitral valve replacement (MVR). Recently, trends for valve replacement are moving towards biological prosthesis also in younger patients, which is justified by the fact that a later valve-in-valve procedure is feasible in the case of degeneration of the tissue valve. This strategy is increasingly recommended in aortic valve surgery but is questionable for MVR. The purpose of this review is to evaluate current guidelines and analyse evidence for biological MVR in patients under 65 years. RECENT FINDINGS: There are differences between guidelines of the American Heart Association and those of the European Society of Cardiology concerning the choice of prostheses in patients undergoing MVR. Although the European Society of Cardiology recommends a mechanical mitral valve in patients under 65 years of age, the American Heart Association does not provide detailed advice for these patients. Mitral valve replacement with biological valves in patients under 65 years is associated with higher rates of reoperation due to structural valve deterioration. In addition, several studies showed a decreased survival after biological MVR. SUMMARY: Evidence for biological MVR in patients less than 65 years without comorbidities or contraindication for oral anticoagulation does not exist. Recommendations for patients less than 65 years of age should not be blurred by current 'en-vogue' methods for promising but not yet proven valve-in-valve strategies.

Reactive oxygen species mediate functional differences in human radial and internal thoracic arteries from smokers.

OBJECTIVE: Smoking not only increases the risk that coronary heart disease will develop but also morbidity and mortality in patients with known coronary atherosclerosis and after coronary artery bypass grafting. Excessive generation of reactive oxygen species (ROS) has been implicated as the final common pathway for the development of endothelial dysfunction in various cardiovascular risk factors. This study assessed the influence of smoking on two different human arteries routinely used as coronary artery bypass graft conduits. METHODS: Isometric tension was recorded on discarded segments of human left internal thoracic artery (ITA) and the radial artery (RA) from smokers and nonsmokers. RESULTS: The contractile response to endothelin-1 was significantly stronger in arteries from smokers than in those from nonsmokers. By contrast, endothelium-dependent relaxant responses to acetylcholine were attenuated in RA rings but enhanced in ITA rings from smokers. In additional experiments, 5-(&6)-chloromethyl-2'-7'-dichlorodihydro-fluorescein diacetate (DCDHF) was used to photochemically detect ROS by confocal imaging of intact ITA and RA. Enhanced production of ROS was induced by exposure of tissues to 28 degrees C. While during exposure to 28 degrees C, basal fluorescence emission was unchanged in ITA rings, it increased significantly in RA rings, indicating enhanced formation of ROS in this peripheral artery. CONCLUSIONS: Data suggest that smoking induces endothelial dysfunction by increasing vascular ROS production. Different levels of endogenous antioxidant enzyme activities and the degree of atherosclerotic changes might modulate physiologic and pharmacologic vasoreactivity and be responsible for decreased graft patency of RA compared with ITA conduits, especially in active smokers.

Human internal thoracic arteries from diabetic patients are resistant to endothelial dysfunction.

The aim of this analysis was to compare vasoreactive properties of internal thoracic arteries (ITA) grafts from diabetic (DM) to those of non-diabetic (ND) patients. Ring segments of ITA, taken from patients undergoing coronary artery bypass grafting, were suspended in organ bath chambers filled with modified Krebs-Henseleit solution and contractile responses to potassium chloride (KCl), noradrenaline (NA), endothelin-1 (ET-l), and endothelium-dependent relaxant responses to acetylcholine (ACH) were recorded isometrically. The receptor-mediated agonists NA and ET-1 stimulated ITA from both groups within similar concentration ranges while ITA from DM patients proved to be significantly more sensitive to KCl than ITA from ND. Furthermore, maximal contractile responses indicated that KCl (3.79 +/- 0.30 g, n = 7 in DM and 2.50 +/- 0.23 g, n = 29 in ND, P < 0.05) evoked significantly higher responses in ITA from DM as compared to the ND control group while both NA and ET-l stimulated ITA from both groups with similar efficacies. Endothelium-dependent relaxant responses to ACH proved to be similar in both groups when expressed as percentages of the pre-existing tone. The present data support the contention that in comparison to ND controls arteries from DM patients are more sensitive to depolarization but endothelial dysfunction is less frequent in human ITA than expected from observations in systemic vascular beds.

Massive intraoperative thrombus of the aortic arch and proximal descending aorta.

A 49-year-old male patient presented with a paravalvular leakage 18 years after aortic valve replacement. The patient received a mechanical valve and was weaned uneventfully from cardiopulmonary bypass. After a drop in the pressure curve of the left radial artery an additional line was placed in the proximal ascending aorta showing normal systemic pressure. Transesophageal echocardiography showed a massive circular thrombosis of the distal aortic arch. The patient received a covered stent to expand the residual aortic lumen and left the hospital in good health.

Activated Rho/Rho kinase and modified calcium sensitivity in cryopreserved human saphenous veins.

BACKGROUND: We have shown previously that cryopreservation of human internal mammary arteries activates protein kinase C and enhances intracellular Ca(2+) [Ca(2+)](i). We now present evidence that in human saphenous veins (HSV) cryoinjury is associated with activation of the Rho/Rho kinase signaling pathways and enhanced [Ca(2+)](i). METHODS: HSV were investigated in vitro either unfrozen within 12h after removal or after storage at -196 degrees C in a cryomedium containing 1.8M dimethyl sulfoxide and 0.1M sucrose as cryoprotectant additives. RESULTS: Cryostorage diminished responses to receptor-mediated contractile agonists such as noradrenaline, 5-HT and endothelin-1 by up to 30% whereas responses to KCl were attenuated by about 50%. Concentration-response curves for CaCl(2) on unfrozen and cryopreserved HSV revealed similar inhibitory activities of both blocking 1,4-dihydropyridine derivatives nifedipine and the (-)-(R) enantiomer of SDZ 202-791 whereas the Ca(2+) channel activating (+)-(S) enantiomer of SDZ 202-791 was 10 times less effective at enhancing contractions to CaCl(2) when tested after cryostorage. These functional effects were reflected by changes in [Ca(2+)](i) as demonstrated by fluorescence of Fluo-3AM loaded veins. The diminished activity of (+)-(S) SDZ 202-791 in cryopreserved HSV was reversed partially when the potassium channel opener pinacidil (1 microM) was present during the freezing/thawing process. Blockade of Rho kinase by HA-1077 proved to be significantly more effective at attenuating contractile responses to both endothelin-1 and KCl after cryostorage. CONCLUSIONS: Data suggested that cryopreservation modified [Ca(2+)](i) of venous smooth muscle cells (1) through depolarization-induced changes in Ca(2+) influx and (2) through activation of Rho kinase signaling pathways.

Impact of freezing/thawing procedures on the post-thaw viability of cryopreserved human saphenous vein conduits.

BACKGROUND: Cryopreserved human blood vessels are important tools in reconstructive surgery. However, patency of frozen/thawed conduits depends largely on the freezing/thawing procedures employed. METHODS: Changes in tone were recorded on rings from human saphenous vein (SV) and used to quantify the degree of cryoinjury after different periods of exposure at room temperature to the cryomedium (Krebs-Henseleit solution containing 1.8M dimethyl sulfoxide and 0.1M sucrose) and after different cooling speeds and thawing rates following storage at -196 degrees C. RESULTS: Without freezing, exposure of SV to the cryomedium for up to 240 min did not modify contractile responses to noradrenaline (NA). Pre-freezing exposure to the cryomedium for 10-120 min attenuated significantly post-thaw maximal contractile responses to NA, endothelin-1 (ET-1) and potassium chloride (KCl) by 30-44%. Exposure for 240 min attenuated post-thaw contractile responses to all tested agents markedly by 62-67%. Optimal post-thaw contractile activity was obtained with SV frozen at about -1.2 degrees C/min and thawed slowly at about 15 degrees C/min. In these SV maximal contractile responses to NA, ET-1 and KCl amounted to 66%, 70% and 60% of that produced by unfrozen controls. Following cryostorage of veins for up to 10 years the responsiveness of vascular smooth muscle to NA was well maintained. CONCLUSION: Cryopreservation allows long-term banking of viable human SV with only minor loss in contractility.

Intraindividual comparison of human radial and internal thoracic arteries in vitro and the effect of preoperative calcium blocker therapy.

The patency rate of radial artery (RA) conduits is considerably lower than that of internal thoracic artery (ITA) grafts and the evidence suggests that this is due to a clinically suspected higher incidence of vasospasm. The aim of this study was, therefore, to compare intraindividually the pharmacological reactivity of RA with that of ITA. Both RA and ITA were taken from the same patients and investigated in parallel. Changes in tone were monitored isometrically on ring preparations from both arteries in organ baths with modified Krebs-Henseleit solution containing 1.25 mm calcium chloride at 1 g passive preload. In intraindividual comparisons maximal receptor-mediated contractile responses to noradrenaline and endothelin-1 and endothelium-dependent acetylcholine-induced relaxant responses revealed no differences between both arteries. By contrast, depolarization-induced contractions to potassium chloride (KCl) appeared to be significantly higher in RA than in ITA. Further analysis, however, revealed that this difference was due to preoperative calcium entry blocker (Ca(2+)eB) therapy. Compared with control tissues, maximal responses to KCl were significantly attenuated in the ITA but unchanged in RA when arteries were obtained from patients with preoperative Ca(2+)eB therapy. The present results suggested that functional responses to pharmacological stimuli of both RA and ITA were quite similar. Preoperative Ca(2+)eB therapy, however, attenuated markedly responses to KCl of the ITA leaving those of RA unchanged. These results, demonstrating a lower sensitivity to Ca(2+)eB of RA, therefore suggested that in addition to Ca(2+)eB other classes of drug may be more effective at reducing the propensity of RA conduits to vasospasm.

OPCAB surgery after right pneumonectomy.

Coronary artery bypass grafting was performed in a 58-year-old patient 3 years after right pneumonectomy for nonsmall cell lung cancer stage IIIa. The CT scan demonstrated a marked shift of the mediastinum into the right chest, but revealed a feasible access to the left coronary artery by median sternotomy. Pulmonary function was impaired. Off-pump coronary artery bypass grafting was performed to avoid cannulation under more difficult conditions and to prevent negative side effects of cardiopulmonary bypass to the pulmonary function. The postoperative recovery was uneventful. We discuss issues related to this special subgroup of patients.

Improved endothelial function after a modified harvesting technique of the internal thoracic artery.

OBJECTIVE: One of the most important factors in bypass surgery is the preservation of endothelial function in the arterial graft. It was of interest, therefore, whether a slightly modified preparation procedure during surgery could contribute to improved endothelial function of the graft. We compared the functional activity of internal thoracic arteries (ITA) prepared according to the traditional harvesting method with occlusion by a clip, dissection at the distal end and storage of the artery in papaverine until its implantation (CA) with the functional activity of arteries which were also prepared and wrapped in papaverine, but were left perfused and dissected immediately before their anastomoses (PA). METHODS: Samples of ITA were obtained from a total number of 28 patients, undergoing bypass surgery, and randomly distributed into two groups. The arteries were cut into rings and suspended in organ baths, containing Krebs-Henseleit solution, for isometric tension recording. Cumulative concentration response curves were determined for the contractile agents endothelin-1 (ET-1), 5-hydroxytryptamine (5-HT), noradrenaline (NA) and potassium chloride (KCl) and the relaxant compounds acetylcholine (ACH) and sodium nitroprusside (SNP) during active tone induced by 30 mM KCl. RESULTS: ET-1 and 5-HT stimulated rings from both groups within the same concentration ranges but elicited significantly (P<0.05) higher contractile responses in CA compared to PA. By contrast, concentration response curves for KCl and NA where nearly superimposable. On the other hand, maximal endothelium-dependent relaxant responses to ACH proved to be significantly stronger in PA (0.84+/-0.20 g) as compared to CA (0.31+/-0.05 g, P<0.05) while endothelium independent relaxant responses to SNP where similar in both groups. CONCLUSION: These data suggest that leaving the ITA perfused during harvesting might improve considerably the endothelial function of the graft.