Assisted circulation using the Tandemheart®, percutaneous transseptal left ventricular assist device, during percutaneous aortic valve implantation: The Rotterdam experience

Aims: The morbidity and mortality of surgical aortic valve replacement are increased in elderly patients with multiple high risk comorbid conditions. Percutaneous prosthetic aortic valve replacement (PAVR) via the femoral arterial approach is feasible in selected patients, who are poor operative candidates, with satisfactory short term outcomes. It is conceivable that patients with poor LV function may benefit from periprocedural cardio-circulatory support. We evaluated the short-term safety and efficacy of using the TandemHeart® PTVA® System (p-LVAD) to deliver extracorporeal circulatory support in patients undergoing PAVR. Methods and results: Between April 2006 and May 2007 the TandemHeart® was used in 10 patients (age: range 64-85, median 80) undergoing elective PAVR using the CoreValve™ Revalving System. The median (range) time for implementation of circulatory support was 32 (22-40) minutes. A pump flow up to 4.6 L/min was achieved. Systemic haemodynamics were maintained in all but one patient. The median (range) systemic arterial pressure (MBP) was 77 (67-89) mmHg at baseline and 76 (61-91) mmHg after pump functioning. A major systolic blood pressure drop (systolic blood pressure < 70 mmHg, pulse pressure < 10 mmHg, occurred in one patient due to PAVR related pericardial tamponade. Median (range) duration of supp

How should I treat acute valve regurgitation?

BACKGROUND: An 81-year-old male with symptoms of angina and dyspnoea (NYHA 3), a history of coronary bypass surgery, a transaortic peak gradient of 109 mmHg on transthoracic echocardiography and a logistic Euro-SCORE of 21.6 was deemed suboptimal for surgery by a multidisciplinary team and was accepted for TAVI. INVESTIGATION: Preprocedural diameter of the native aortic root was 24.4 mm on transthoracic echocardiography (TTE), 26.9 mm on contrast angiography and 26.8 mm by 30.2 mm on multislice computed tomography (MSCT). DIAGNOSIS: Heavy calcification of the aortic root and coronary arteries by MSCT. TREATMENT: Transcatheter aortic valve replacement with an 29 mm CoreValve prosthesis

Relationship between the logistic EuroSCORE and the Society of Thoracic Surgeons Predicted Risk of Mortality score in patients implanted with the CoreValve ReValving system--a Bern-Rotterdam Study

Background Surgical risk scores, such as the logistic EuroSCORE (LES) and Society of Thoracic Surgeons Predicted Risk of Mortality (STS) score, are commonly used to identify high-risk or “inoperable” patients for transcatheter aortic valve implantation (TAVI). In Europe, the LES plays an important role in selecting patients for implantation with the Medtronic CoreValve System. What is less clear, however, is the role of the STS score of these patients and the relationship between the LES and STS. Objective The purpose of this study is to examine the correlation between LES and STS scores and their performance characteristics in high-risk surgical patients implanted with the Medtronic CoreValve System. Methods All consecutive patients (n = 168) in whom a CoreValve bioprosthesis was implanted between November 2005 and June 2009 at 2 centers (Bern University Hospital, Bern, Switzerland, and Erasmus Medical Center, Rotterdam, The Netherlands) were included for analysis. Patient demographics were recorded in a prospective database. Logistic EuroSCORE and STS scores were calculated on a prospective and retrospective basis, respectively. Results Observed mortality was 11.1%. The mean LES was 3 times higher than the mean STS score (LES 20.2% ± 13.9% vs STS 6.7% ± 5.8%). Based on the various LES and STS cutoff values used in previous and ongoing TAVI trials, 53% of patients had an LES ≥15%, 16% had an STS ≥10%, and 40% had an LES ≥20% or STS ≥10%. Pearson correlation coefficient revealed a reasonable (moderate) linear relationship between the LES and STS scores, r = 0.58, P < .001. Although the STS score outperformed the LES, both models had suboptimal discriminatory power (c-statistic, 0.49 for LES and 0.69 for STS) and calibration. Conclusions Clinical judgment and the Heart Team concept should play a key role in selecting patients for TAVI, whereas currently available surgical risk score algorithms should be used to guide clinical decision making

A comparison of patient characteristics and 30-day mortality outcomes after transcatheter aortic valve implantation and surgical aortic valve replacement for the treatment of aortic stenosis: A two-centre study

Aims: It is unclear whether transcatheter aortic valve implantation (TAVI) addresses an unmet clinical need for those currently rejected for surgical aortic valve replacement (SAVR) and whether there is a subgroup of high-risk patients benefiting more from TAVI compared to SAVR. In this two-centre, prospective cohort study, we compared baseline characteristics and 30-day mortality between TAVI and SAVR in consecutive patients undergoing invasive treatment for aortic stenosis. Methods and results: We pre-specified different adjustment methods to examine the effect of TAVI as compared with SAVR on overall 30-day mortality: crude univariable logistic regression analysis, multivariable analysis adjusted for baseline characteristics, analysis adjusted for propensity scores, propensity score matched analysis, and weighted analysis using the inverse probability of treatment (IPT) as weights. A total of 1,122 patients were included in the study: 114 undergoing TAVI and 1,008 patients undergoing SAVR. The crude mortality rate was greater in the TAVI group (9.6% vs. 2.3%) yielding an odds ratio [OR] of 4.57 (95%-CI 2.17-9.65). Compared to patients undergoing SAVR, patients with TAVI were older, more likely to be in NYHA class III and IV, and had a considerably higher logistic EuroSCORE and more comorbid conditions. Adjusted OR depended on the method used to control for confounding and ranged from 0.60 (0.11-3.36) to 7.57 (0.91-63.0). We examined the distribution of propensity scores and found scores to overlap sufficiently only in a narrow range. In patients with sufficient overlap of propensity scores, adjusted OR ranged from 0.35 (0.04-2.72) to 3.17 (0.31 to 31.9). In patients with insufficient overlap, we consistently found increased odds of death associated with TAVI compared with SAVR irrespective of the method used to control confounding, with adjusted OR ranging from 5.88 (0.67-51.8) to 25.7 (0.88-750). Approximately one third of patients undergoing TAVI were found to be potentially eligible for a randomised comparison of TAVI versus SAVR. Conclusions: Both measured and unmeasured confounding limit the conclusions that can be drawn from observational comparisons of TAVI versus SAVR. Our study indicates that TAVI could be associated with either substantial benefits or harms. Randomised comparisons of TAVI versus SAVR are warranted

Mutations in 2 distinct genetic pathways result in cerebral cavernous malformations in mice

Cerebral cavernous malformations (CCMs) are a common type of vascular malformation in the brain that are a major cause of hemorrhagic stroke. This condition has been independently linked to 3 separate genes: Krev1 interaction trapped (KRIT1), Cerebral cavernous malformation 2 (CCM2), and Programmed cell death 10 (PDCD10). Despite the commonality in disease pathology caused by mutations in these 3 genes, we found that the loss of Pdcd10 results in significantly different developmental, cell biological, and signaling phenotypes from those seen in the absence of Ccm2 and Krit1. PDCD10 bound to germinal center kinase III (GCKIII) family members, a subset of serine-threonine kinases, and facilitated lumen formation by endothelial cells both in vivo and in vitro. These findings suggest that CCM may be a common tissue manifestation of distinct mechanistic pathways. Nevertheless, loss of heterozygosity (LOH) for either Pdcd10 or Ccm2 resulted in CCMs in mice. The murine phenotype induced by loss of either protein reproduced all of the key clinical features observed in human patients with CCM, as determined by direct comparison with genotype-specific human surgical specimens. These results suggest that CCM may be more effectively treated by directing therapies based on the underlying genetic mutation rather than treating the condition as a single clinical entity

Separating Electrophilicity and Lewis Acidity: The Synthesis, Characterization, and Electrochemistry of the Electron Deficient Tris(aryl)boranes B(C6F5)3–n(C6Cl5)n (n= 1–3)

A new family of electron-deficient tris(aryl)boranes, B(C(6)F(5))(3-n)(C(6)Cl(5))(n) (n = 1-3), has been synthesized, permitting an investigation into the steric and electronic effects resulting from the gradual replacement of C(6)F(5) with C(6)Cl(5) ligands. B(C(6)F(5))(2)(C(6)Cl(5)) (3) is accessed via C(6)Cl(5)BBr(2), itself prepared from donor-free Zn(C(6)Cl(5))(2) and BBr(3). Reaction of C(6)Cl(5)Li with BCl(3) in a Et(2)O/hexane slurry selectively produced B(C(6)Cl(5))(2)Cl, which undergoes B-Cl exchange with CuC(6)F(5) to afford B(C(6)F(5))(C(6)Cl(5))(2) (5). While 3 forms a complex with H(2)O, which can be rapidly removed under vacuum or in the presence of molecular sieves, B(C(6)Cl(5))(3) (6) is completely stable to refluxing toluene/H(2)O for several days. Compounds 3, 5, and 6 have been structurally characterized using single crystal X-ray diffraction and represent the first structure determinations for compounds featuring B-C(6)Cl(5) bonds; each exhibits a trigonal planar geometry about B, despite having different ligand sets. The spectroscopic characterization using (11)B, (19)F, and (13)C NMR indicates that the boron center becomes more electron-deficient as n increases. Optimized structures of B(C(6)F(5))(3-n)(C(6)Cl(5))(n) (n = 0-3) using density functional theory (B3LYP/TZVP) are all fully consistent with the experimental structural data. Computed (11)B shielding constants also replicate the experimental trend almost quantitatively, and the computed natural charges on the boron center increase in the order n = 0 (0.81) < n = 1 (0.89) < n = 2 (1.02) < n = 3 (1.16), supporting the hypothesis that electrophilicity increases concomitantly with substitution of C(6)F(5) for C(6)Cl(5). The direct solution cyclic voltammetry of B(C(6)F(5))(3) has been obtained for the first time and electrochemical measurements upon the entire series B(C(6)F(5))(3-n)(C(6)Cl(5))(n) (n = 0-3) corroborate the spectroscopic data, revealing C(6)Cl(5) to be a more electron-withdrawing group than C(6)F(5), with a ca. +200 mV shift observed in the reduction potential per C(6)F(5) group replaced. Conversely, use of the Guttmann-Beckett and Childs' methods to determine Lewis acidity on B(C(6)F(5))(3), 3, and 5 showed this property to diminish with increasing C(6)Cl(5) content, which is attributed to the steric effects of the bulky C(6)Cl(5) substituents. This conflict is ascribed to the minimal structural reorganization in the radical anions upon reduction during cyclic voltammetric experiments. Reduction of 6 using Na((s)) in THF results in a vivid blue paramagnetic solution of Na(+) [6](•-); the EPR signal of Na(+)[6](•-) is centered at g = 2.002 with a((11)B) 10G. Measurements of the exponential decay of the EPR signal (298 K) reveal [6](•-) to be considerably more stable than its perfluoro analogue

Autoimmune Subepidermal Bullous Diseases of the Skin and Mucosae: Clinical Features, Diagnosis, and Management.

Autoimmune subepidermal blistering diseases of the skin and mucosae constitute a large group of sometimes devastating diseases, encompassing bullous pemphigoid, gestational pemphigoid, mucous membrane pemphigoid, epidermolysis bullosa acquisita, and anti-p200 pemphigoid. Their clinical presentation is polymorphic. These autoimmune blistering diseases are associated with autoantibodies that target distinct components of the basement membrane zone of stratified epithelia. These autoantigens represent structural proteins important for maintenance of dermo-epidermal integrity. Bullous pemphigoid (BP) is the most common subepidermal autoimmune blistering disease of the skin and mucosae. Although the disease typically presents with a generalized blistering eruption associated with itch, atypical variants with either localized bullous lesions or "non-bullous" presentations are observed in approximately 20% of patients. A peculiar form of BP typically associated with pregnancy is pemphigoid gestationis. In anti-p200 pemphigoid, patients present with tense blisters on erythematosus or normal skin resembling BP, with a predilection for acral surfaces. These patients have antibodies targeting the 200-kDa basement membrane protein. Epidermolysis bullosa is a rare autoimmune blistering disease associated with autoantibodies against type VII collagen that can have several phenotypes including a classical form mimicking dystrophic epidermolysis bullosa, an inflammatory presentation mimicking BP, or mucous membrane pemphigoid-like lesions. Mucous membrane pemphigoid (MMP) is the term agreed upon by international consensus for an autoimmune blistering disorder, which affects one or more mucous membrane and may involve the skin. The condition involves a number of different autoantigens in the basement membrane zone. It may result in severe complications from scarring, such as blindness and strictures. Diagnosis of these diseases relies on direct immunofluorescence microscopy studies and immunoserological assays. Management of affected patients is often challenging. We will here review the clinical and immunopathological features as well as the pathophysiology of this group of organ-specific autoimmune diseases. Finally, we will discuss the diagnostic approach and the principles of management in clinical practice