Matthias Siepe

Prosthesis Oversizing in Balloon-Expandable Transcatheter Aortic Valve Implantation Is Associated With Contained Rupture of the Aortic Root

Background— To retrospectively investigate the potential cause of contained rupture of the aortic root in balloon-expandable transcatheter aortic valve implantation (TAVI) by means of pre- and postinterventional multislice computed tomography. Methods and Results— Seventy-two patients (mean age 82±7 years, mean aortic valve area 0.69±0.19 cm2) underwent balloon-expandable TAVI using the EdwardsSAPIEN Transcatheter Heart Valve (23 mm, n=19; 26 mm, n=50; 29 mm, n=3). Aortic annulus dimensions were quantified by multislice computed tomography–based cross-sectional area assessment and average diameter calculation (CAAD) before and after TAVI. Post-TAVI multislice computed tomography data sets were available in 65 patients; contained aortic root rupture was diagnosed in 3 patients. Pre-TAVI CAAD was 23.1±1.8 mm; post-TAVI CAAD was 22.9±1.3 mm. Median relative change in CAAD pre- and post-TAVI was −0.5% (interquartile range, 3.6%). Relative increase of 5% to 10% was observed in 4 patients (1 with contained rupture), relative increase >10% in 2 patients, both with contained rupture. Mean relative oversizing, calculated as the relative difference in diameter between pre-TAVI CAAD and nominal diameter of the selected prosthesis, was 9.8%±7.8%. Relative oversizing was significantly higher in patients with contained rupture compared with patients without contained rupture (24.6%±5.4% versus 9.1%±6.6%; P<0.001). Relative oversizing ≥20% occurred in 6 patients (3 with contained rupture). Conclusions— Contained rupture of the aortic root in balloon-expandable TAVI is associated with severe prosthesis oversizing. Multislice computed tomography–based assessment of aortic annulus dimension in conjunction with adapted sizing guidelines may reduce the incidence of severe oversizing.

Assessment of aortic annulus dimensions for Edwards SAPIEN Transapical Heart Valve implantation by computed tomography: calculating average diameter using a virtual ring method

OBJECTIVE Accurate preoperative assessment of the aortic annulus dimensions is critical in patients undergoing transcatheter aortic valve implantation (TAVI) for severe AS. Using multislice computed tomography (MSCT), we evaluated a novel approach to quantify aortic annulus dimensions using cross-sectional area (CSA) assessment and average diameter calculation compared with the commonly applied electronic caliper measurements in patients undergoing transapical implantation of the Edwards SAPIEN Transcatheter Heart Valve. METHODS Seventy-one patients underwent pre-TAVI MSCT with the following dimensions assessed at the level of the most basal attachment points of all three aortic cusps joined by a virtual ring: CSA, calculated average annulus diameter (CAAD), and minimal, maximum, sagittal and coronal diameters. Measurements were compared with post-TAVI MSCT data sets at the level of the ventricular stent ending in 24 patients. Pre-TAVI measurements were compared to those taken post-TAVI. Eligibility to balloon-expandable TAVI was evaluated based on the different measurements. RESULTS The Edwards SAPIEN valve (23 mm, n=8; 26 mm, n=16) was implanted 2.1±1.1 mm below the non-coronary sinus. Pre-TAVI CAAD was 23.0±1.6 mm; post-TAVI CAAD was 23.0±1.1 mm. Post-TAVI CSA was circular in 18 patients (75%) and ovoid in six (25%). Pre- and post-TAVI assessment showed strong correlation for CSA and CAAD (r=0.835, p<0.001; r=0.841, p<0.001, respectively). Minimal, maximum, coronal and sagittal dimension correlated weakly between pre- and post-TAVI measurements (r=0.435-0.632, p=0.001-0.034). CONCLUSION Pre-TAVI CSA assessment and average diameter calculation using a virtual ring method is able to predict the post-interventional configuration of the annulus after balloon-expandable TAVI. We regard this approach as the best-available method to select the appropriate prosthesis size for balloon-expandable TAVI. Specific MSCT-based sizing recommendations should be developed.

Hydrogel-based engineered skeletal muscle grafts normalize heart function early after myocardial infarction

Tissue engineering represents an attractive approach for the treatment of congestive heart failure. The influence of the differentiation of myogenic graft for functional recovery is not defined. We engineered a biodegradable skeletal muscle graft (ESMG) tissue and investigated its functional effect after implantation on the epicardium of an infarcted heart segment. ESMGs were synthesized by mixing collagen (2 mg/mL), Matrigel (2 mg/mL), and rat skeletal muscle cells (10(6)). Qualitative and quantitative aspects of ESMGs were optimized. Two weeks following coronary ligation, the animals were randomized in three groups: ESMG glued to the epicardial surface with fibrin (ESMG, n = 7), fibrin alone (fibrin, n = 5), or sham operation (sham, n = 4). Echocardiography, histology, and immunostaining were performed 4 weeks later. A cohesive three-dimensional tissular structure formed in vitro within 1 week. Myoblasts differentiated into randomly oriented myotubes. Four weeks postimplantation, ESMGs were vascularized and invaded by granulation tissue. Mean fractional shortening (FS) was, however, significantly increased in the ESMG group as compared with preimplantation values (42 +/- 6 vs. 33 +/- 5%, P < 0.05) and reached the values of controlled noninfarcted animals (control, n = 5; 45 +/- 3%; not significant). Pre- and postimplantation FS did not change over these 4 weeks in the sham group and the fibrin-treated animals. This study showed that it is possible to improve systolic heart function following myocardial infarction through implantation of differentiated muscle fibers seeded on a gel-type scaffold despite a low rate of survival.

How does the ascending aorta geometry change when it dissects

OBJECTIVES The purpose of this study is to delineate changes in aortic geometry and diameter due to dissection. BACKGROUND Aortic diameter is the major criterion for elective ascending aortic replacement for dilated ascending aortas to prevent aortic dissection. However, recommendations are made on the basis of clinical experience and observation of diameters of previously dissected aortas. METHODS Six tertiary centers on 2 continents reviewed their acute aortic dissection type A databases, which contained 1,821 patients. Included were all non-Marfan patients with nonbicuspid aortic valves who had undergone computed tomography angiography <2 years before and within 12 h after aortic dissection onset. Aortic geometry before and after dissection onset were compared. RESULTS Altogether, 63 patients were included (27 spontaneous and 36 retrograde dissections, median age 68 [57; 77] years; 54% were men). In all but 1 patient, maximum ascending aortic diameter was <55 mm before aortic dissection onset. The largest increase in diameter and volume induced by the dissection were observed in the ascending aorta (40.1 [36.6; 45.3] mm vs. 52.9 [46.1; 58.6] mm, +12.8 mm; p < 0.001; 124.0 [90.8; 162.5] cm(3) vs. 171.0 [147.0; 197.0] cm(3), +47 cm(3); p < 0.001). Mean aortic arch diameter increased from 39.8 (30.5; 42.6) mm to 46.4 (42.0; 51.6) mm (+6.6 mm; p < 0.001) and descending thoracic aorta diameter from 31.2 (27.0; 33.3) mm to 34.9 (30.9; 39.5) mm (+3.7 mm; p < 0.001). Changes in thoracic aorta geometry were similar for spontaneous and retrograde etiology. CONCLUSIONS Geometry of the thoracic aorta is affected by aortic dissection, leading to an increase in diameter that is most pronounced in the ascending aorta. Both spontaneous and retrograde dissection result in similar aortic geometry changes.

Acute aortic dissection type A: age-related management and outcomes reported in the German Registry for Acute Aortic Dissection Type A (GERAADA) of over 2000 patients.

Objective:To determine the association between age and clinical presentation, management and surgical outcomes in a large contemporary, prospective cohort of patients with acute aortic dissection type A (AADA). Background:AADA is one of the most life-threatening cardiovascular diseases, and delayed surgery or overly conservative management can result in sudden death. Methods:The perioperative and intraoperative conditions of 2137 patients prospectively reported to the multicenter German Registry for Acute Aortic Dissection Type A were analyzed. Results:Of all patients with AADA, 640 (30%) were 70 years or older and 160 patients (7%) were younger than 40 years. The probability of aortic dissection extension to the supra-aortic vessels and abdominal aorta decreased with age (P < 0.0001 and P = 0.0017, respectively). In 1447 patients (69%), the aortic root was preserved and supracoronary replacement of the ascending aorta was done. The probability of this procedure increased with age (P < 0.0001). The incidence of new postoperative neurological disorders was not influenced by age. The lowest probability of 30-day mortality was noted in the youngest patients (11%–14% for patients aged between 20 and 40 years) and rose progressively with age, peaking at 25% in octogenarians. Conclusions:This study reflects current results after surgical treatment of AADA in relation to patient age. Current survival rates are acceptable, even in very elderly patients. The contemporary surgical mortality rate among young patients is lower than that previously reported in the literature. The postoperative stroke incidence does not increase with age.

Conformational Pulsatile Changes of the Aortic Annulus: Impact on Prosthesis Sizing by Computed Tomography for Transcatheter Aortic Valve Replacement

OBJECTIVES This study sought to investigate pulsatile changes of the aortic annulus and their impact on prosthesis selection by computed tomography (CT). BACKGROUND Precise noninvasive prosthesis sizing is a prerequisite for transcatheter aortic valve replacement. METHODS A total of 110 patients with severe aortic stenosis (mean age: 82.9 ± 8 years, mean aortic valve area: 0.69 ± 0.18 cm(2)) underwent electrocardiogram-gated CT. Aortic annulus dimensions were planimetrically quantified as area-derived diameter (D(A) = 2 ×✓(CSA/π), where CSA is the cross-sectional area) and perimeter-derived diameter (D(P) = P/π, where P is the length of the perimeter) in 5% increments of the RR interval. Hypothetical prosthesis sizing was based on D(A) and D(P) (23-mm prosthesis for <22 mm; 26 mm: 22 to 25 mm; 29 mm: >25 mm) and compared between maximum and traditional cardiac CT reconstruction phases at 35% and 75% of RR. Agreement for prosthesis selection was calculated by κ statistics. RESULTS D(A) and D(P) were increased and eccentricity was reduced during systole, with D(A-MAX) and D(P-MAX) most often observed at 20% of RR. D(P) was consistently larger than D(A). Average net differences were 2.0 ± 0.6 mm and 1.7 ± 0.5 mm by D(A-MIN) versus D(A-MAX) and D(P-MIN) versus D(P-MAX). Agreement for prosthesis sizing was found in 93 of 110 patients (κ = 0.75) by D(A-75%) and in 80 of 110 patients (κ = 0.53) by D(A-MAX) compared with D(A-35%); and in 94 of 110 patients (κ = 0.73) by D(P-75%) and in 93 of 110 patients (κ = 0.73) by D(P-MAX) compared with D(P-35%). With sizing by D(A-75%) or D(P-75%), nominal prosthesis diameter was smaller than D(A-MAX) or D(P-MAX) in 15 and 6 patients respectively. CONCLUSIONS Aortic annulus morphology exhibits conformational pulsatile changes throughout the cardiac cycle due to deformation and stretch. These changes affect prosthesis selection. Prosthesis selection by diastolic perimeter- or area-derived dimensions harbors the risk of undersizing.

Pulsatile Pulmonary Perfusion During Cardiopulmonary Bypass Reduces the Pulmonary Inflammatory Response

BACKGROUND Pulmonary dysfunction presumably linked to an inflammatory response is frequent after cardiac operations using cardiopulmonary bypass (CPB) and pulmonary hypoperfusion. We previously demonstrated that active perfusion of the lungs during CPB reduces ischemic lung injury. We now hypothesized that avoiding ischemia of the lungs during CPB by active pulmonary perfusion would decrease pulmonary inflammatory response. METHODS Pigs were randomized to a control group with CPB for 120 minutes, followed by 120 minutes of postbypass reperfusion, or to the study groups where animals underwent active pulmonary perfusion with pulsatile or nonpulsatile perfusion during CPB (n = 7 in each group). Activation of transcription factor activity (nuclear factor [NF]-kappaB and activating protein [AP]-1) was determined by electrophoretic mobility shift assay. Levels of proinflammatory protein expression (interleukin [IL]-1, IL-6, and tumor necrosis factor [TNF]-alpha) were quantified by enzyme-linked immunoabsorbent assay. Caspase-3 activity was measured using a fluorogenic assay. RESULTS The activation of transcription factor AP-1 and NF-kappaB was reduced in the pulsatile pulmonary perfusion group. The caspase-3 activity and the expression of IL-1, IL-6, and TNF-alpha revealed a significant decrease in the pulsatile and nonpulsatile pulmonary perfusion groups. Animals of the pulsatile pulmonary perfusion group showed significantly reduced IL-6 expression and caspase-3 activity compared with the nonpulsatile pulmonary perfusion group. CONCLUSIONS Active pulmonary perfusion reduces the inflammatory response and apoptosis in the lungs observed during conventional CPB. This effect is greatest when pulmonary perfusion is performed with pulsatility. The reduction in cytokine expression by pulsatile pulmonary perfusion might be mediated by AP-1 and NF-kappaB.

Carbon Monoxide Inhalation Reduces Pulmonary Inflammatory Response during Cardiopulmonary Bypass in Pigs

Background:Cardiopulmonary bypass (CPB) is associated with pulmonary inflammation and dysfunction. This may lead to acute lung injury and acute respiratory distress syndrome with increased morbidity and mortality. The authors hypothesized that inhaled carbon monoxide before initiation of CPB would reduce inflammatory response in the lungs. Methods:In a porcine model, a beating-heart CPB was used. The animals were either randomized to a control group, to standard CPB, or to CPB plus carbon monoxide. In the latter group, lungs were ventilated with 250 ppm inhaled carbon monoxide in addition to standard ventilation before CPB. Lung tissue samples were obtained at various time points, and pulmonary cytokine levels were determined. Results:Hemodynamic parameters were largely unaffected by CPB or carbon monoxide inhalation. There were no significant differences in cytokine expression in mononuclear cells between the groups throughout the experimental time course. Compared with standard CPB animals, carbon monoxide significantly suppresses tumor necrosis factor-&agr; and interleukin-1&bgr; levels (P < 0.05) and induced the antiinflammatory cytokine interleukin 10 (P < 0.001). Carbon monoxide inhalation modulates effector caspase activity in lung tissue during CPB. Conclusions:The results demonstrate that inhaled carbon monoxide significantly reduces CPB-induced inflammation via suppression of tumor necrosis factor &agr;, and interleukin-1&bgr; expression and elevation of interleukin 10. Apoptosis induced by CPB was associated with caspase-3 activation and was significantly attenuated by carbon monoxide treatment. Based on the observations of this study, inhaled carbon monoxide could represent a potential new therapeutic modality for counteracting CPB-induced lung injury.

Polyurethane Scaffolds Seeded With Genetically Engineered Skeletal Myoblasts: A Promising Tool to Regenerate Myocardial Function

In animal models, intramyocardial injection of primary skeletal myoblasts is supposed to promote tissue regeneration and to improve cardiac function after myocardial infarction. The usage of genetically engineered myoblasts overexpressing the paracrine factors involved in tissue repair is believed to enhance these effects. However, cell therapy via injection is always accompanied by a high death rate of the injected cells. Here, we describe the construction of a growth factor-producing myoblast-seeded scaffold to overcome this limitation. Skeletal myoblasts were isolated and expanded from newborn Lewis rats. Cells were seeded on polyurethane (PU) scaffolds (Artelon) and transfected with DNA of VEGF-A, HGF, SDF-1, or Akt1 using the lipid-based Metafectene Pro method. Overexpression was verified by ELISA, RT-PCR (VEGF-A, HGF, and SDF-1) and Western blot analysis (Akt1). The seeded scaffolds were transplanted onto damaged myocardium of Lewis rats 2 weeks after myocardial infarction. Six weeks later, their therapeutic potential in vivo was analyzed by measurement of infarction size and capillary density. Primary rat skeletal myoblasts seeded on PU scaffolds were efficiently transfected, achieving transfection rates of 20%. In vitro, we noted a significant increase in expression of VEGF-A, HGF, SDF-1, and Akt1 after transfection. In vivo, transplantation of growth factor-producing myoblast-seeded scaffolds resulted in enhanced angiogenesis (VEGF-A, HGF, and Akt1) or a reduced infarction zone (SDF-1 and Akt1) in the ischemically damaged myocardium. In summary, we constructed a growth factor-producing myoblast-seeded scaffold which combines the beneficial potential of stem cell transplantation with the promising effects of gene-therapeutic approaches. Because this matrix also allows us to circumvent previous cell application drawbacks, it may represent a promising tool for tissue regeneration and the re-establishment of cardiac function after myocardial infarction.

Supracoronary ascending aortic replacement in patients with acute aortic dissection type A: What happens to the aortic root in the long run?

OBJECTIVE Our objective was to determine long-term outcome predictors for patients with acute aortic dissection type A (AADA) and aortic root involvement. METHODS From 2001 through 2009, 119 of 152 patients operated on for AADA at a tertiary medical center underwent supracoronary ascending aortic replacement (52 women; mean age, 61 ± 15 years). Those with at least 1-year follow-up (n = 97) were retrospectively assessed for preoperative aortic root disease. Follow-up data were assessed for evidence of new-onset aortic root disease by computed tomography and echocardiography, and for reoperation for aortic root disease. RESULTS Median follow-up was 33.8 months (range, 0-112 months). Twenty-six (27%) patients had new-onset aortic root disease at 4.4 ± 2.6 years after the initial procedure (range, 1.0-8.2 years) and 10 required aortic root reoperation. Severe aortic dissection with extension to pelvic arteries was an independent predictor for new-onset aortic root disease (P < .01). Dissection of all aortic sinuses during the initial procedure was an independent predictor (P < .05) for aortic root reoperation. Mean rate of aortic root expansion after supracoronary repair was 0.6 ± 1.1 mm per year. Preoperative aortic root diameter and aortic sinus dissection did not affect survivals. Five-year survivals were similar in patients with and without new-onset aortic root disease (91% vs 89%; P = .79). CONCLUSIONS In patients with AADA, dissection of 3 aortic sinuses is an independent predictor for need of reoperation, whereas dissection extension into the iliac arteries is a predictor of secondary aortic root disease. Long-term follow-up at close intervals is warranted in patients with supracoronary ascending aortic replacement to reduce mortality caused by new onset of aortic root disease.