Faiz Ramjankhan

Transcatheter Aortic Valve Implantation With the New Balloon-Expandable Sapien 3 Versus Sapien XT Valve System A Propensity Score–Matched Single-Center Comparison

Background—The new balloon-expandable Sapien 3 transcatheter heart valve (S3-THV) incorporates new features to reduce aortic regurgitation (AR) and vascular complications in transcatheter aortic valve implantation. Aim of this study is to compare the outcomes of the S3-THV with the preceding Sapien XT THV (SXT-THV) in patients who underwent transcatheter aortic valve implantation for symptomatic severe native aortic stenosis. Methods and Results—Eligible patients were retrospectively identified in our institutional database and periprocedural clinical and imaging data were collected. Non-parsimonious one-to-many propensity score matching was performed to account for differences in baseline characteristics. Between November 2011 and December 2014, 167 patients underwent balloon-expandable transcatheter aortic valve implantation with either the S3-THV (n=49) or SXT-THV (n=118). Forty-four (89.8%) S3-THV patients were matched to 66 (55.9%) SXT-THV patients (mean age 80.3±8.4 and 80.5±7.8 years, median EuroSCORE 15.8 and 16.5%, respectively). In the S3-THV and SXT-THV groups, transfemoral approach (77.3% versus 78.8%) and postdilatation rates (15.9% versus 12.1%) were similar. Predischarge echocardiography demonstrated a lower incidence of ≥mild AR (15.9% versus 46.2%, P=0.003) for the S3-THV, despite reduced annulus area to prosthesis oversizing (8.2±5.1 versus 18.2±10.7%, P=0.001). Transfemoral access site–related life-threatening or major bleedings and vascular complications were absent in the S3-THV group (0% versus 7.7%, P=0.15). No differences were observed in pacemaker implantation rate (9.8% versus 8.8%, P=0.94) and 30-day mortality (both 5%). Conclusions—In this retrospective, propensity score–matched analysis, the S3-THV performed superiorly to the SXT-THV, as demonstrated by improved valve patency and increased transfemoral access safety.

Embrella embolic deflection device for cerebral protection during transcatheter aortic valve replacement.

AIMS To compare the extent of cerebral ischemic injury after transcatheter aortic valve replacement (TAVR) with the use of an Embrella Embolic Deflector System versus unprotected TAVR. METHODS Fifteen patients with severe symptomatic aortic stenosis underwent TAVR with use of the Embrella Embolic Deflector System for cerebral protection. Cerebral diffusion-weighted magnetic resonance imaging (DWI) was performed in all patients at day 4 after the procedure and images were retrospectively compared to 37 patients who had previously undergone TAVR without a protection device (TAVR-only group). RESULTS Successful placement of the Embrella device was achieved in all patients. DWI revealed an increase in the number of ischemic lesions in the Embrella group compared with the TAVR-only group (9.0 vs 5.0, P = .044). The use of the Embrella device was however associated with a significant reduction in single-lesion volume: 9.7 μL [5.8, 18.4] versus 17.8 μL [9.5, 38.7] (P < .001). Moreover, total infarct volumes of more than 1000 μL were only seen in the TAVR-only group. More lesions occurred in the right side of the brain in the Embrella group, whereas in the TAVR-only group lesions were distributed equally between left and right. One patient in the TAVR-only group suffered from a transient ischemic attack. Postoperative evaluation was clinically uneventful in the Embrella group. CONCLUSIONS The use of the Embrella device during TAVR increased the number of cerebral ischemic lesions on postprocedural brain imaging. This increase in number was however accompanied by a significant reduction in single-lesion volume and the absence of large total infarct volumes.

Different types of cultured human adult cardiac progenitor cells have a high degree of transcriptome similarity.

The discovery and isolation of different resident cardiac progenitor cells (CPCs) a decade ago, as described by several research groups, stimulated the use of these cells for cardiac regeneration. Human CPCs are moving towards the clinic as one of the most promising cell types for cardiac repair, but the extent to which their molecular profiles vary as a result of donor heterogeneity or different isolation methods remain unclear. Defining a common molecular profile that defines CPC’s is therefore an important goal. Similarly, identifying robust and multilaboratory isolation and culture protocols that generate reproducible cell populations from genetically diverse donors is critical for their translational success. In this respect, we collected human auricle biopsy samples anonymously from 20 different adult patients that underwent bypass surgery and generated a total number of 33 different cardiac derived progenitor cell (CPC) lines (Table S1). Human CPCs were isolated according the original published protocol, based on c-kit 1 or Sca-1 2 expression or auricles were cut in 1 mm3 parts and cultured as explants to obtain Cardiospheres (CSps) 3 and Cardiosphere Derived Cells (CDCs) 4. CPCs were subsequently propagated in a panel of different media formulations, either in their originally described culture media or switched to media and culture coatings of the other CPC subsets (Figure S1, Table S7). When comparing individual CPC cell-lines, isolated with different methodologies, they shared a high degree of similarities and correlation in gene expression patterns (Fig. ​(Fig.1B).1B). By averaging expression profiles of individual CPC conditions, thereby reducing donor variability, similarities increased even more, ranging from 0.92 to 0.96 (Fig. ​(Fig.1C;1C; Table S2). These results suggest that individual donor differences were larger than influences of isolation and medium conditions. Moreover, the strongest correlations between the different CPC lines were observed when cells were isolated and cultured in the same conditions. Among the different CPCs, spheres-growing CSps showed the least correlation (0.91–0.96), while monolayer-growing CPCs shared higher correlations among them (0.96–0.98). We performed a moderated t-test to evaluate significant differentially expressed genes between the individual samples (Tables S3 and S4). Out of the 13,073 analysd genes, we found only few genes differentially expressed in 5 of 20 different monolayer-cultured CPC cell-lines comparisons. Only when the 3D-cultured CSps were compared with the other CPCs more differently expressed genes could be identified. Although only limited genes were different, we further explored if we could identify differences in gene patterns between the different CPC populations, based on selected genes important for stem cell-maintenance, their growth and biology. In particular, we evaluated genes involved in the regulation of different stem cell pathways like TGF-β, Wnt, NFkB, p53, JAK/STAT, Notch and Hedgehog (Fig. S2A), cell cycle (Fig. S2B), stem cell transcription factors (Fig. S2C), and growth factors, cytokines and chemokines (Fig. S2D). Detailed heat map analysis showed again; however, a very similar profile among all samples, with small differences mainly related to individual donors and not to different cell types or conditions (Fig. S2). Since CSps and monolayer growing CPCs have differently expressed patterns, we selected all the significantly differentially expressed genes that displayed a two fold or more difference and compared them with CDCs, and c-Kit and Sca-1+ CPCs monolayer-cultures (Table S6). Ingenuity pathway analysis identified a gene network in CSps that is enriched in genes encoding for growth factor production and signalling molecules involved in the development of cardiac muscle, vasculogenesis and angiogenesis (Fig. ​(Fig.2).2). Among them BMP-2, HGF, LIF, PTGS-2, VEGFA and PDGFRB are known to play an important role during cardiac development. Moreover, having a protective effect on a developing heart failure. Figure 1 Experimental design of the project (A) and hierarchical clustering of CPCs samples (B and C). Sca-1+ cells were isolated from human auricle biopsy and cultured in gelatin coated flask and Sca-1 medium (Sca GEL S-MED) (2) (d). After expansion cells were ... Figure 2 Ingenuity molecular networks analysis of the differentially expressed genes. Fold difference ≥2; p<0.05. (A) Differentially regulated genes between CSps and Sca GEL SP++ in Cardiovascular System Development and Function, Embryonic Development, ... Taken together, our data suggest that human CPCs can be isolated from patient heart biopsies using different markers, such as c-kit or Sca-1- like, and alternative methodologies, via direct cell isolation or via explant culture, such as CSps and CDCs. For the first time, however, we showed that upon culture expansion, these cell populations have a very similar gene expression profile, even more pronounced when cultured in comparable culture conditions and even transcended by donor differences. Among the different CPCs analysed, CSps are the most different, probably because of the unselected cell populations and containing more supporting cell population that form CSps and their particular 3D culture structure and thereby different interactions and growing conditions. Surprisingly CDCs, which is a cell population derived from CSps, are more similar with other antigen selected CPCs rather than with CSps, confirming the idea that monolayer and high proliferative culture condition might play an important role in minimizing the differences among the different CPCs analysed. Recently, Dey et al. isolated murine CPCs, based on different surface markers 5, and showed that these, non-cultured cells, represent progenitor cell populations at different stages of cardiac commitment 5. In our study, we did not observe such differences between the different human monolayer CPCs population upon culture propagation. A similar stage difference, however, might be present in situ in humans as well but lost upon culture expansion. The expression of these different stem cell markers and their co-expression probably represent different developmental and/or physiological stages of CPCs, rather than intrinsic different CPC populations. For future translation for cardiac cell therapy, our results suggest that we need to take into account the cell donor variability between patients more than the isolation methodology, and further study the correlation between CPC characteristics and e.g. the diseased status of a patient. Our findings are of fundamental importance to create a consensus among different scientists in the field of myocardial regeneration, which should help align future clinical approaches to improve the reported beneficial effects of cell therapy for heart disease by using cardiac derived progenitor cell populations.

Analysis of aortic valve commissural fusion after support with continuous-flow left ventricular assist device

OBJECTIVES Continuous-flow left ventricular assist devices (cf-LVADs) may induce commissural fusion of the aortic valve leaflets. Factors associated with this occurrence of commissural fusion are unknown. The aim of this study was to examine histological characteristics of cf-LVAD-induced commissural fusion in relation to clinical variables. METHODS Gross and histopathological examinations were performed on 19 hearts from patients supported by either HeartMate II (n = 17) or HeartWare (n = 2) cf-LVADs and related to clinical characteristics (14 heart transplantation, 5 autopsy). RESULTS Eleven of the 19 (58%) aortic valves showed fusion of single or multiple commissures (total fusion length 11 mm [4-20] (median [interquartile range]) per valve), some leading to noticeable nodular displacements or considerable lumen diameter narrowing. Multiple fenestrations were observed in one valve. Histopathological examination confirmed commissural fusion, with varying changes in valve layer structure without evidence of inflammatory infiltration at the site of fusion. Commissural fusion was associated with continuous aortic valve closure during cf-LVAD support (P = 0.03). LVAD-induced aortic valve insufficiency developed in all patients with commissural fusion and in 67% of patients without fusion. Age, duration of cf-LVAD support and aetiology of heart failure (ischaemic vs dilated cardiomyopathy) were not associated with the degree of fusion. CONCLUSIONS Aortic valve commissural fusion after support with cf-LVADs is a non-inflammatory process leading to changes in valve layer structure that can be observed in >50% of cf-LVAD patients. This is the first study showing that patients receiving full cf-LVAD support without opening of the valve have a significantly higher risk of developing commissural fusion than patients on partial support.

Single-centre experience of 85 patients with a continuous-flow left ventricular assist device: clinical practice and outcome after extended support

OBJECTIVES We evaluated our single-centre clinical experience with the HeartMate II (HM II) left ventricular assist device (LVAD) as a bridge to transplantation (BTT) in end-stage heart failure (HF) patients. METHODS Survival rates, echocardiographic parameters, laboratory values and adverse events of 85 consecutive patients supported with a HM II were evaluated. RESULTS Overall, mean age was 45 ± 13 years, 62 (73%) were male and non-ischaemic dilatated cardiomyopathy was present in 60 (71%) patients. The median duration of mechanical support was 387 days (IQR 150-600), with a range of 1-1835 days. The 6-month, 1-, 2-, 3- and 4-year survival rates during HM II LVAD support were 85, 81, 76, 76 and 68%, respectively. Echocardiographic parameters demonstrated effective left ventricular unloading, while laboratory results reflected adequate organ perfusion. However, HM II support was associated with adverse events, such as infections in 42 patients (49%; 0.67 events/patient-year), cardiac arrhythmia in 44 (52%; 0.86 events/patient-year), bleeding complications in 32 (38%; 0.43 events/patient-year) and neurological dysfunction in 17 (20%; 0.19 events/patient-year). CONCLUSIONS In view of the increasing shortage of donor hearts, HM II LVAD support may be considered a life-saving treatment in end-stage HF patients, with good survival. However, it is still associated with some serious adverse events, of which neurological complications are the most critical.

End-stage heart failure and mechanical circulatory support: feasibility of discharge from hospital.

Background. Due to the shortage of donor hearts, mechanical circulatory support is increasingly being used as a bridge to transplantation. In order to allow for more widespread use of ventricular assist devices it is mandatory that patients are not continuously hospitalised. We present the results of our experience with patients with end-stage heart failure, discharged from hospital after implantation of a ventricular assist device and followed in an outpatient setting.Methods. After an intensive training and education programme, focusing on the management of the percutaneous driveline and instructions on how to handle in case of an alarm or malfunction of the device, patients were discharged. They were followed in the outpatient department. All regular and unplanned visits were registered, including readmissions.Results. Twenty-seven patients treated with a ventricular assist device were discharged from hospital. There were 37 extra visits, of these, 27 were device related resulting in 21 readmissions (0.78/patient). We treated eight infectious episodes in four patients, all device related. Furthermore seven thromboembolic episodes occurred in four patients. One patient died because of multiorgan failure seven weeks after he was readmitted with an urosepsis. In our experience of 11.4 patient years at home while on the device, only 5% of the time was spent in hospital for complications. In comparison with patients on an assist device who stayed in hospital until transplantation, there were no more complications. Conclusion. This study demonstrates that patients with end-stage heart failure, treated with a ventricular assist device, can be safely discharged from hospital, with an acceptable rate of readmissions. It results in a fair quality of life, with a high degree of independence of the patient. (Neth Heart J 2007; 15:45-50.)

TriGuard™ HDH embolic deflection device for cerebral protection during transcatheter aortic valve replacement

This study aims to evaluate the safety and performance of the new embolic deflection device TriGuard™HDH in patients undergoing TAVR.

systemic embolisation as presentation and recurrence of cardiac myxoma two years after surgery

Primary cardiac tumours are rare when compared with metastatic involvement. The majority of primary cardiac tumours are benign and in adults the majority of these masses are myxomas. The treatment is surgical removal because of the risk of embolisation and/or cardiovascular complications. We describe a female presenting with systemic embolisation and recurrence of cardiac myxoma after surgery. Recurrence of myxoma is rare after surgery in case of solitary tumours but more frequent in patients with familial myxomas in association with the Carney complex. Genetic analysis revealed a mutation in the PRKAR1A gene that has never been described before. (Neth Heart J 2010;18:499-502.)

Advanced Strategies for End-Stage Heart Failure: Combining Regenerative Approaches with LVAD, a New Horizon?

Despite the improved treatment of cardiovascular diseases, the population with end-stage heart failure (HF) is progressively growing. The scarcity of the gold standard therapy, heart transplantation, demands novel therapeutic approaches. For patients awaiting transplantation, ventricular-assist devices have been of great benefit on survival. To allow explantation of the assist device and obviate heart transplantation, sufficient and durable myocardial recovery is necessary. However, explant rates so far are low. Combining mechanical circulatory support with regenerative therapies such as cell (-based) therapy and biomaterials might give rise to improved long-term results. Although synergistic effects are suggested with mechanical support and stem cell therapy, evidence in both preclinical and clinical setting is lacking. This review focuses on advanced and innovative strategies for the treatment of end-stage HF and furthermore appraises clinical experience with combined strategies.

Soluble ST2 in end‐stage heart failure, before and after support with a left ventricular assist device

The interleukin‐33 (IL‐33)/suppressor of tumorigenicity 2 (ST2) pathway is suggested to play an important role in fibrosis, remodelling and the progression of heart failure (HF). Increased soluble (sST2) levels are associated with adverse outcome in the average HF population. Less is known about sST2 levels in end‐stage HF. Therefore, we studied sST2 levels in end‐stage HF and the effect of unloading by left ventricular assist device (LVAD) support on sST2 levels.