Dan Spiegelstein

Patient Characteristics and Cell Source Determine the Number of Isolated Human Cardiac Progenitor Cells

Background— The identification and isolation of human cardiac progenitor cells (hCPCs) offer new approaches for myocardial regeneration and repair. Still, the optimal source of human cardiac progenitor cells and the influence of patient characteristics on their number remain unclear. Using a novel method to isolate human cardiac progenitor cells, we aimed to define the optimal source and association between their number and patient characteristics. Methods and Results— We developed a novel isolation method that produced viable cells (7×106±6.53×105/g) from various tissue samples obtained during heart surgery or endomyocardial biopsies (113 samples from 94 patients 23 to 80 years of age). The isolated cardiac cells were grown in culture with a stem cell expansion medium. According to fluorescence-activated cell sorting analysis, cultured cells derived from the right atrium generated higher amounts of c-kit+ (24±2.5%) and Islet-1+ cells (7%) in culture (mean of passages 1, 2, and 3) than did cultured cells from the left atrium (7.3±3.5%), right ventricle (4.1±1.6%), and left ventricle (9.7±3%; P=0.001). According to multivariable analysis, the right atrium as the cell source and female sex were associated with a higher number of c-kit+ cells. There was no overlap between c-kit+ and Islet-1 expression. In vitro assays of differentiation into osteoblasts, adipocytes, and myogenic lineage showed that the isolated human cardiac progenitor cells were multipotent. Finally, the cells were transplanted into infarcted myocardium of rats and generated myocardial grafts. Conclusion— Our results show that the right atrium is the best source for c-kit+ and Islet-1 progenitors, with higher percentages of c-kit+ cells being produced by women.

Deformation Dynamics and Mechanical Properties of the Aortic Annulus by 4-Dimensional Computed Tomography Insights Into the Functional Anatomy of the Aortic Valve Complex and Implications for Transcatheter Aortic Valve Therapy

OBJECTIVES The purpose of this study was to assess deformation dynamics and in vivo mechanical properties of the aortic annulus throughout the cardiac cycle. BACKGROUND Understanding dynamic aspects of functional aortic valve anatomy is important for beating-heart transcatheter aortic valve implantation. METHODS Thirty-five patients with aortic stenosis and 11 normal subjects underwent 256-slice computed tomography. The aortic annulus plane was reconstructed in 10% increments over the cardiac cycle. For each phase, minimum diameter, ellipticity index, cross-sectional area (CSA), and perimeter (Perim) were measured. In a subset of 10 patients, Youngs elastic module was calculated from the stress-strain relationship of the annulus. RESULTS In both subjects with normal and with calcified aortic valves, minimum diameter increased in systole (12.3 ± 7.3% and 9.8 ± 3.4%, respectively; p < 0.001), and ellipticity index decreased (12.7 ± 8.8% and 10.3 ± 2.7%, respectively; p < 0.001). The CSA increased by 11.2 ± 5.4% and 6.2 ± 4.8%, respectively (p < 0.001). Perim increase was negligible in patients with calcified valves (0.56 ± 0.85%; p < 0.001) and small even in normal subjects (2.2 ± 2.2%; p = 0.01). Accordingly, relative percentage differences between maximum and minimum values were significantly smallest for Perim compared with all other parameters. Youngs modulus was calculated as 22.6 ± 9.2 MPa in patients and 13.8 ± 6.4 MPa in normal subjects. CONCLUSIONS The aortic annulus, generally elliptic, assumes a more round shape in systole, thus increasing CSA without substantial change in perimeter. Perimeter changes are negligible in patients with calcified valves, because tissue properties allow very little expansion. Aortic annulus perimeter appears therefore ideally suited for accurate sizing in transcatheter aortic valve implantation.

Quality of mitral valve repair: Median sternotomy versus port-access approach

OBJECTIVES We sought to compare early and late clinical and echocardiographic outcomes of patients undergoing minimally invasive mitral valve repair by means of the port-access and median sternotomy approaches. METHODS Between 2000 and 2009, 503 patients had mitral valve repair, of whom 143 underwent surgical intervention for isolated posterior leaflet pathology: 61 through port access and 82 through median sternotomy. The port-access group had better preoperative New York Heart Association functional class (P = .007) and a higher rate of elective cases (97% vs 87%, P = .037). Other preoperative characteristics were similar between the groups, including mitral valve pathology and repair techniques. RESULTS Operative, bypass, and clamp times were significantly longer in the port-access group. Mean hospital stay was 5.3 +/- 2.5 days in the port-access group versus 5.7 +/- 2.5 days in the median sternotomy group (P = .4). Early postoperative echocardiographic analysis showed that most patients in both groups had none or trivial mitral regurgitation and none of the patients had greater than grade 2 mitral regurgitation. Follow-up extended for up to 100 months (mean, 34 +/- 24 months). New York Heart Association class improved in both groups (P = .394). Freedom from reoperation was 97% and 95% in the port-access and median sternotomy groups, respectively. Late echocardiographic analysis revealed that 82% (49/60) in the port-access group and 91% (73/80) in the median sternotomy group were free from moderate or severe mitral regurgitation (P = .11). CONCLUSIONS In isolated posterior mitral valve pathology, quality of mitral valve repair with the port-access approach can compare with that with the conventional median sternotomy approach.

Inverse Relationship Between Membranous Septal Length and the Risk of Atrioventricular Block in Patients Undergoing Transcatheter Aortic Valve Implantation.

OBJECTIVES This study sought to examine whether imaging of the atrioventricular (AV) membranous septum (MS) by computed tomography (CT) can be used to identify patient-specific anatomic risk of high-degree AV block and permanent pacemaker (PPM) implantation before transcatheter aortic valve implantation (TAVI) with self-expandable valves. BACKGROUND MS length represents an anatomic surrogate of the distance between the aortic annulus and the bundle of His and may therefore be inversely related to the risk of conduction system abnormalities after TAVI. METHODS Seventy-three consecutive patients with severe aortic stenosis underwent contrast-enhanced CT before TAVI. The aortic annulus, aortic valve, and AV junction were assessed, and MS length was measured in the coronal view. RESULTS In 13 patients (18%), high-degree AV block developed, and 21 patients (29%) received a PPM. Multivariable logistic regression analysis revealed MS length as the most powerful pre-procedural independent predictor of high-degree AV block (odds ratio [OR]: 1.35, 95% confidence interval [CI]: 1.1 to 1.7, p = 0.01) and PPM implantation (OR: 1.43, 95% CI: 1.1 to 1.8, p = 0.002). When taking into account pre- and post-procedural parameters, the difference between MS length and implantation depth emerged as the most powerful independent predictor of high-degree AV block (OR: 1.4, 95% CI: 1.2 to 1.7, p < 0.001), whereas the difference between MS length and implantation depth and calcification in the basal septum were the most powerful independent predictors of PPM implantation (OR: 1.39, 95% CI: 1.2 to 1.7, p < 0.001 and OR: 4.9, 95% CI: 1.2 to 20.5, p = 0.03; respectively). CONCLUSIONS Short MS, insufficient difference between MS length and implantation depth, and the presence of calcification in the basal septum, factors that may all facilitate mechanical compression of the conduction tissue by the implanted valve, predict conduction abnormalities after TAVI with self-expandable valves. CT assessment of membranous septal anatomy provides unique pre-procedural information about the patient-specific propensity for the risk of AV block.

Late clinical outcome of transient intraoperative systolic anterior motion post mitral valve repair.

OBJECTIVE Systolic anterior motion (SAM) after mitral valve repair with significant mitral regurgitation requires immediate reintervention. Transient SAM immediately after repair is usually managed by hemodynamic maneuvers. We investigated the late clinical and echocardiographic significance of postoperative transient SAM. METHODS Between 2004 and 2013, mitral valve repair was performed on 549 consecutive patients with degenerative mitral valve disease. Of the 45 patients (8.2%) identified with postrepair SAM, 5 needed immediate reintervention. Hemodynamic maneuvers, such as preload and afterload augmentation and rate control, effectively abolished SAM in 40 patients (SAM). They were followed and compared with the remaining 509 patients (non-SAM). RESULTS Mean clinical follow-up was 54 ± 28 and 31 ± 26 months and was available in 100% and 95% (SAM and non-SAM) patients, respectively. One hospital death occurred in each group (P = .14). At follow-up, 2 patients (0.3%) showed significant SAM with left ventricular outflow tract obstruction, which resolved in 1 patient after beta-blocker therapy. SAM patients underwent exercise stress echocardiography: 1 patient showed left ventricular outflow tract obstruction that worsened after exercise. At 5 years, freedom from moderate or severe mitral regurgitation and New York Heart Association functional class III-IV was 85% versus 92% (P = .27) and 81% versus 92% (P = .15), and freedom from reoperation was 100% and 96% (P = .4), in SAM and non-SAM patients, respectively. CONCLUSIONS Late postoperative exercise stress echocardiogram revealed low incidence of SAM in patients with immediate postrepair transient SAM. All other late clinical outcomes were similar to those of non-SAM repair patients. Conservative management of intraoperative transient SAM is both successful and reliable.

Midterm Results of Mitral Valve Repair: Closed Versus Open Annuloplasty Ring

BACKGROUND Closed and open annuloplasty rings are both used for mitral valve repair. This study compared the clinical and echocardiographic results in patients with degenerative mitral disease undergoing MV repair with closed semirigid rings vs open bands. METHODS Between 2004 and 2008, 377 patients (mean age, 59 + or - 12 years) underwent mitral valve repair. Valve pathology was degenerative in 273 (72%). Closed rings were used in 163 (60%) and open rings in 110 (40%). Patients had similar characteristics and comorbidities. In addition to annuloplasty, repair techniques included leaflet resection (48% and 77%, p < 0.01), artificial chordal (55% and 36%, p < 0.01), and edge-to-edge repair (4% and 4%, p = 0.79), in closed and open groups, respectively. RESULTS One patient in each group died (0.7%). Mean follow-up was 19 + or - 14 (closed group) and 34 + or - 15 months (open group; p < 0.01). Freedom from reoperation was 97.5% (closed group) vs 96.5% (open group). At follow-up, New York Heart Association functional class was similar between groups, and 91% in the closed group and 84% in the open group were free from moderate or severe mitral regurgitation (p = 0.05). Closed group patients had a longer line of leaflet coaptation (9.1 + or - 2.7 mm) vs the open group (7.1 + or - 1.9 mm; p < 0.01). CONCLUSIONS Patients with closed semirigid annuloplasty rings demonstrated significantly longer lines of leaflet coaptation and tendency toward better echocardiographic midterm results than patients with open bands and may, therefore, benefit from improved repair durability.

Comparison of acute kidney injury classifications in patients undergoing transcatheter aortic valve implantation: Predictors and long-term outcomes

Acute kidney injury (AKI) was demonstrated to adversely affect outcome in patients undergoing transcatheter aortic valve implantation (TAVI). We compared predictors for AKI and associated outcomes according to various definitions among patients undergoing TAVI in a tertiary medical center.

Albumin correlates with all-cause mortality in elderly patients undergoing transcatheter aortic valve implantation

AIMS Albumin is a marker of frailty. Scarce data are available on correlations between frailty-related parameters and outcomes in patients undergoing TAVI. This study sought to evaluate the relation between albumin and mortality in TAVI candidates. METHODS AND RESULTS A total of 150 patients (mean age 81±6 years) undergoing TAVI were included in the study. Patients with pre-procedural albumin >4 g/dl (>40 g/L) (n=71) were compared to those ≤4 g/dl (≤40 g/L) (n=79). The cut-off value of 4 g/dl (40 g/L) was based on the mean value of albumin in the patients included in the study. During a mean follow-up of 2.1 years the survival rate was 72%. Patients in both groups had similar baseline characteristics. The 2.1-year mortality was higher in the low albumin group compared with the normal albumin group (35% vs. 19%, p=0.01). Multivariate analysis indicated that low pre-procedural albumin was independently associated with a more than twofold increase in 2.1-year all-cause mortality (p=0.01, HR=2.28; 95% CI: 1.17-4.44). Low post-procedural serum albumin remained a strong parameter correlated with all-cause mortality (HR=2.47; 95% CI: 1.28-4.78; p<0.01). CONCLUSIONS Baseline albumin can be used as a simple tool that correlates with survival after TAVI. Low albumin is an important parameter associated with all-cause mortality after the procedure.

Preoperative Hematocrit as a Predictor of Perioperative Morbidities Following Nonemergent Coronary Artery Bypass Surgery

Preoperative hematocrit (HCT) has predicted inferior outcome following cardiac surgery. However, the potential for preoperative HCT to be a marker for sicker patients was not well explored. This study examined the impact of HCT on outcome following nonemergent coronary artery bypass grafting (CABG) and whether the association is modified by operative risk or intraoperative blood transfusion.

Operative risk and preoperative hematocrit in bypass graft surgery: Role of gender and blood transfusion.

BACKGROUND The association between lower preoperative hematocrit (Hct) and risk for morbidity/mortality after cardiac surgery is well established. We examined whether the impact of low preoperative Hct on outcome is modified by blood transfusion and operative risk in women and men undergoing nonemergent CABG surgery. METHODS Patients having nonemergent, first-time, isolated CABG were included (N=2757). Logistic regressions assessed effect of hematocrit on major perioperative morbidity/mortality separately by males (n=2232) and females (n=525). RESULTS Mean age was 63.2±10.1years, preoperative hematocrit was 38.9±4.8%, and STS risk score was 1.3±1.8%. Blood transfusion was more likely in female patients (26% vs. 12%, P<0.001). Multivariate analyses revealed that lower body mass index and lower preoperative hematocrit predicted transfusion in males and females, whereas older age (OR=1.03, P=0.017) also predicted transfusion in females. Major morbidity was also more likely in female patients (12% vs. 7%, P<0.001). In multivariate analyses, blood transfusion was the only predictive factor for major morbidity in females (OR=4.56, P<0.001). In males, higher body mass index (OR=1.07, P<0.001), lower hematocrit (OR=0.94, P=0.017), interaction of STS score with hematocrit (OR=1.02, P=0.045), and blood transfusion (OR=9.22, P<0.001) were significant predictors for major morbidity. CONCLUSIONS This study showed females were more likely to have blood transfusion and major morbidities after nonemergent CABG. Traditional factors that have been found to predict outcomes, such as hematocrit and STS risk, were related only to major morbidity in male patients. However, blood transfusion negatively impacted major outcome after nonemergent CABG surgery across all STS risk levels in both genders.