All Publications


  • Genetic architecture of cardiac dynamic flow volumes. Nature genetics Gomes, B., Singh, A., O'Sullivan, J. W., Schnurr, T. M., Goddard, P. C., Loong, S., Amar, D., Hughes, J. W., Kostur, M., Haddad, F., Salerno, M., Foo, R., Montgomery, S. B., Parikh, V. N., Meder, B., Ashley, E. A. 2023

    Abstract

    Cardiac blood flow is a critical determinant of human health. However, the definition of its genetic architecture is limited by the technical challenge of capturing dynamic flow volumes from cardiac imaging at scale. We present DeepFlow, a deep-learning system to extract cardiac flow and volumes from phase-contrast cardiac magnetic resonance imaging. A mixed-linear model applied to 37,653 individuals from the UK Biobank reveals genome-wide significant associations across cardiac dynamic flow volumes spanning from aortic forward velocity to aortic regurgitation fraction. Mendelian randomization reveals a causal role for aortic root size in aortic valve regurgitation. Among the most significant contributing variants, localizing genes (near ELN, PRDM6 and ADAMTS7) are implicated in connective tissue and blood pressure pathways. Here we show that DeepFlow cardiac flow phenotyping at scale, combined with genotyping data, reinforces the contribution of connective tissue genes, blood pressure and root size to aortic valve function.

    View details for DOI 10.1038/s41588-023-01587-5

    View details for PubMedID 38082205

    View details for PubMedCentralID 7612636

  • Defining left ventricular remodeling using lean body mass allometry: a UK Biobank study. European journal of applied physiology Gomes, B., Hedman, K., Kuznetsova, T., Cauwenberghs, N., Hsu, D., Kobayashi, Y., Ingelsson, E., Oxborough, D., George, K., Salerno, M., Ashley, E., Haddad, F. 2023

    Abstract

    PURPOSE: The geometric patterns of ventricular remodeling are determined using indexed left ventricular mass (LVM), end-diastolic volume (LVEDV) and concentricity, most often measured using the mass-to-volume ratio (MVR). The aims of this study were to validate lean body mass (LBM)-based allometric coefficients for scaling and to determine an index of concentricity that is independent of both volume and LBM.METHODS: Participants from the UK Biobank who underwent both CMR and dual-energy X-ray absorptiometry (DXA) during 2014-2015 were considered (n=5064). We excluded participants aged≥70years or those with cardiometabolic risk factors. We determined allometric coefficients for scaling using linear regression of the logarithmically transformed ventricular remodeling parameters. We further defined a multiplicative allometric relationship for LV concentricity (LVC) adjusting for both LVEDV and LBM.RESULTS: A total of 1638 individuals (1057 female) were included. In subjects with lower body fat percentage (<25% in males,<35% in females, n=644), the LBM allometric coefficients for scaling LVM and LVEDV were 0.85±0.06 and 0.85±0.03 respectively (R2=0.61 and 0.57, P<0.001), with no evidence of sex-allometry interaction. While the MVR was independent of LBM, it demonstrated a negative association with LVEDV in (females: r=-0.44, P<0.001; males: -0.38, P<0.001). In contrast, LVC was independent of both LVEDV and LBM [LVC=LVM/(LVEDV0.40*LBM0.50)] leading to increased overlap between LV hypertrophy and higher concentricity.CONCLUSIONS: We validated allometric coefficients for LBM-based scaling for CMR indexed parameters relevant for classifying geometric patterns of ventricular remodeling.

    View details for DOI 10.1007/s00421-022-05125-9

    View details for PubMedID 36617359

  • Machine learning-based risk prediction of intrahospital clinical outcomes in patients undergoing TAVI CLINICAL RESEARCH IN CARDIOLOGY Gomes, B., Pilz, M., Reich, C., Leuschner, F., Konstandin, M., Katus, H. A., Meder, B. 2021; 110 (3): 343-356

    Abstract

    Currently, patient selection in TAVI is based upon a multidisciplinary heart team assessment of patient comorbidities and surgical risk stratification. In an era of increasing need for precision medicine and quickly expanding TAVI indications, machine learning has shown promise in making accurate predictions of clinical outcomes. This study aims to predict different intrahospital clinical outcomes in patients undergoing TAVI using a machine learning-based approach. The main clinical outcomes include all-cause mortality, stroke, major vascular complications, paravalvular leakage, and new pacemaker implantations.The dataset consists of 451 consecutive patients undergoing elective TAVI between February 2014 and June 2016. The applied machine learning methods were neural networks, support vector machines, and random forests. Their performance was evaluated using five-fold nested cross-validation. Considering all 83 features, the performance of all machine learning models in predicting all-cause intrahospital mortality (AUC 0.94-0.97) was significantly higher than both the STS risk score (AUC 0.64), the STS/ACC TAVR score (AUC 0.65), and all machine learning models using baseline characteristics only (AUC 0.72-0.82). Using an extreme boosting gradient, baseline troponin T was found to be the most important feature among all input variables. Overall, after feature selection, there was a slightly inferior performance. Stroke, major vascular complications, paravalvular leakage, and new pacemaker implantations could not be accurately predicted.Machine learning has the potential to improve patient selection and risk management of interventional cardiovascular procedures, as it is capable of making superior predictions compared to current logistic risk scores.

    View details for DOI 10.1007/s00392-020-01691-0

    View details for Web of Science ID 000543118400002

    View details for PubMedID 32583062

    View details for PubMedCentralID 6386402

  • Prevalence and relevance of impaired left ventricular function in chronic moderate regurgitation of native aortic valves ACTA CARDIOLOGICA Gomes, B., Hees, K., Hund, H., Mereles, D., Meder, B., Katus, H. A., Bekeredjian, R. 2020; 75 (7): 613-620

    Abstract

    Background: Reduced ejection fraction (EF) in chronic moderate aortic regurgitation (AR) could be either due to a late remodelling response after longstanding moderate AR, or could represent a specific phenotype of cardiomyopathy (CMP) with concomitant AR. The aim of this study was to analyse progression of left ventricular (LV) impairment in moderate AR.Methods: All patients in our echocardiography database between 2005 and 2016 were screened to identify pure chronic moderate AR, excluding significant coronary artery disease (CAD) or concomitant valve disease. Remaining 152 patients were divided into three groups: (a) preserved systolic LV function; (b) reduced LV EF and prediagnosed concomitant cardiomyopathy (CMP); (c) reduced LV EF without prediagnosed CMP.Results: The majority patients (group A = 66%) had preserved systolic LV function, remaining oligosymptomatic with stable LVEDD at follow-up. Non-CMP patients with reduced EF at baseline (group C = 18%) were significantly older (group C: 74 vs. group A: 61 years, p < .001) whereas left ventricular end-diastolic diameter (LVEDD) significantly increased over time (p = .046). Development of renal insufficiency, atrial fibrillation and NYHA > II were significant risk factors linked to the worsening of LV function in patients with moderate AR.Conclusion: Preserved LV EF and LVEDD remain stable over a long lasting period in the majority of patients. However, these data suggest that some patients develop reduced LV EF, even without progression of AR to severe, especially if renal insufficiency or atrial fibrillation are present.

    View details for DOI 10.1080/00015385.2019.1639964

    View details for Web of Science ID 000476191500001

    View details for PubMedID 31311434

  • Transfemoral aortic valve replacement for severe aortic valve regurgitation in a patient with a pulsatile-flow biventricular assist device ESC HEART FAILURE Gomes, B., Bekeredjian, R., Leuschner, F., Ehlermann, P., Schmack, B., Ruhparwar, A., Raake, P. W., Katus, H. A., Kreusser, M. M. 2019; 6 (1): 217-221

    Abstract

    Severe aortic regurgitation (AR) is a rare but significant complication of ventricular assist device therapy. Experience with transcatheter aortic valve replacement (TAVR) in this setting of patients is very limited, while the scarcely reported cases exclusively refer to TAVR under continuous-flow left ventricular assist devices. Here, we present the first successful TAVR while running a pulsatile-flow biventricular assist device (PF-BiVAD). Clinical data were collected based on the patient's electronic medical records after the patient's consent was obtained. We describe the case of a 57-year-old man in whom a PF-BiVAD (EXCOR, Berlin Heart, Berlin, Germany) had been initially inserted after fulminant myocarditis with subsequent severe dilated cardiomyopathy as bridge-to-transplantation therapy. Over the following 2 years, the patient developed severe de novo AR under PF-BiVAD therapy. This, along with progressive cardiac decompensation, led to the decision for TAVR by our heart team as a minimal invasive approach for severe AR. TAVR using two Edwards SAPIEN 3 bioprostheses as a valve-in-valve procedure resulted in a significant reduction of AR from severe to mild, with trace paravalvular leakage and without significant pressure gradients. The patient underwent total orthotopic heart transplantation afterwards. This is the first report of successful TAVR in a patient with severe de novo AR while running a PF-BiVAD.

    View details for DOI 10.1002/ehf2.12384

    View details for Web of Science ID 000459632300026

    View details for PubMedID 30479049

    View details for PubMedCentralID PMC6351890

  • Periprocedural antibiotic treatment in transvascular aortic valve replacement JOURNAL OF INTERVENTIONAL CARDIOLOGY Gomes, B., Geis, N. A., Leuschner, F., Meder, B., Konstandin, M., Katus, H. A., Bekeredjian, R. 2018; 31 (6): 885-890

    Abstract

    To date, there are no guidelines recommending a specific prophylactic antibiotic treatment in transcatheter aortic valve replacement (TAVR). The aim of this study is to evaluate clinical data after TAVR with different periprocedural antibiotic regimens.In May 2015 the institutional rules for periprocedural antibiotic prophylaxis were changed from 3 days to 1 day. Thus, a total of 450 consecutive TAVR patients between February 2014 and June 2016 were classified into two intention-to-treat groups: patients receiving a 1-day Cefuroxime prophylaxis (N = 225); patients receiving a 3-day Cefuroxime prophylaxis (N = 225).One-day Cefuroxime regimen was not associated with shorter hospitalization (3-day Cefuroxime 9 ± 4.7 vs 1-day Cefuroxime 8.9 ± 4.0; P = 0.87). Incidence of diarrhea (26.2% vs 18.2%; P = 0.04) and Clostridium difficile infections (4% vs 0.4%; P = 0.01) were significantly higher in the 3-day group. No endocarditis was registered after 1 year follow-up. There was no difference in 30-day overall mortality rate, major vascular complications, bleeding complications, pacemaker-implantation rate, paravalvular regurgitation, or acute kidney injury between patients groups.Three-day Cefuroxime prophylaxis does not seem to be advantageous compared to a shorter 1-day regimen, but even shows a significantly higher incidence of diarrhea and Clostridium difficile infection.

    View details for DOI 10.1111/joic.12567

    View details for Web of Science ID 000452122900022

    View details for PubMedID 30397939

  • Atrial fibrillation and heart failure-associated remodeling of two-pore-domain potassium (K<sub>2P</sub>) channels in murine disease models: focus on TASK-1 BASIC RESEARCH IN CARDIOLOGY Wiedmann, F., Schulte, J. S., Gomes, B., Zafeiriou, M., Ratte, A., Rathjens, F., Fehrmann, E., Scholz, B., Voigt, N., Mueller, F., Thomas, D., Katus, H. A., Schmidt, C. 2018; 113 (4): 27

    Abstract

    Understanding molecular mechanisms involved in atrial tissue remodeling and arrhythmogenesis in atrial fibrillation (AF) is essential for developing specific therapeutic approaches. Two-pore-domain potassium (K2P) channels modulate cellular excitability, and TASK-1 (K2P3.1) currents were recently shown to alter atrial action potential duration in AF and heart failure (HF). Finding animal models of AF that closely resemble pathophysiological alterations in human is a challenging task. This study aimed to analyze murine cardiac expression patterns of K2P channels and to assess modulation of K2P channel expression in murine models of AF and HF. Expression of cardiac K2P channels was quantified by real-time qPCR and immunoblot in mouse models of AF [cAMP-response element modulator (CREM)-IbΔC-X transgenic animals] or HF (cardiac dysfunction induced by transverse aortic constriction, TAC). Cloned murine, human, and porcine TASK-1 channels were heterologously expressed in Xenopus laevis oocytes. Two-electrode voltage clamp experiments were used for functional characterization. In murine models, among members of the K2P channel family, TASK-1 expression displayed highest levels in both atrial and ventricular tissue samples. Furthermore, K2P2.1, K2P5.1, and K2P6.1 showed significant expression levels. In CREM-transgenic mice, atrial expression of TASK-1 was significantly reduced in comparison with wild-type animals. In a murine model of TAC-induced pressure overload, ventricular TASK-1 expression remained unchanged, while atrial TASK-1 levels were significantly downregulated. When heterologously expressed in Xenopus oocytes, currents of murine, porcine, and human TASK-1 displayed similar characteristics. TASK-1 channels display robust cardiac expression in mice. Murine, porcine, and human TASK-1 channels share functional similarities. Dysregulation of atrial TASK-1 expression in murine AF and HF models suggests a mechanistic contribution to arrhythmogenesis.

    View details for DOI 10.1007/s00395-018-0687-9

    View details for Web of Science ID 000434774700003

    View details for PubMedID 29881975

  • First experience with the 34 mm self-expanding Evolut R in a multicentre registry EUROINTERVENTION Harnath, A., Gomes, B., Herwig, V., Gatto, F., Watremez, S., Katus, H. A., Bekeredjian, R. 2018; 14 (3): 298-300

    View details for DOI 10.4244/EIJ-D-18-00137

    View details for Web of Science ID 000439423800012

    View details for PubMedID 29633938

  • Procedural advantages of a novel coronary stent design with ultra-thin struts and bioabsorbable abluminal polymer coating in an all-comers registry POSTEPY W KARDIOLOGII INTERWENCYJNEJ Abu Sharar, H., Gomes, B., Chorianopoulos, E., Kaya, Z., Gleissner, C. A., Katus, H. A., Bekeredjian, R. 2018; 14 (3): 240-246

    Abstract

    The implications of novel drug-eluting stent (DES) design modifications including ultra-thin struts and new concepts of polymer coating for procedural efficacy are still unknown.To evaluate procedural efficacy and short-term safety of a novel DES design.In this all-comers registry, 407 consecutive patients were enrolled upon undergoing percutaneous coronary interventions (PCI) with the thin-strut bioabsorbable abluminal polymer-coated SYNERGY stent. These patients were then compared with the previous 407 patients undergoing PCI performed by the same interventionalists using currently established second-generation DES (Promus Element plus, Xience prime, Resolute Integrity). Several clinical and procedural data were compared, and the coronary artery complexity was assessed by the American College of Cardiology/American Heart Association classification and SYNTAX Score.The study population consisted of 814 patients. A total of 859 Synergy stents were deployed in 480 target vessels in the Synergy group (n = 407), and 904 stents in 469 vessels in the second-generation DES group (n = 407). Coincidentally, target lesions in the Synergy group (A 2.7%, B1 13.8%, B2 38.6%, C 45.0%) were more complex (p < 0.01) than those in the second-generation DES group (A 4.9%, B1 18.7%, B2 42.3%, C 34.2%). In cases with severe lesions (B2/C), the median contrast agent amount and fluoroscopy time were significantly lower in the Synergy group, indicating improved deliverability (110 ml vs. 150 ml; p < 0.01 and 7.2 min vs. 9.1 min; p = 0.01). Rates of in-hospital major adverse cardiovascular events were comparable between the two groups.In an all-comers, real-world PCI population, novel stent design modifications including ultra-thin struts and abluminal bioabsorbable polymer coating are associated with improved procedural performance.

    View details for DOI 10.5114/aic.2018.78326

    View details for Web of Science ID 000445242800005

    View details for PubMedID 30302099

    View details for PubMedCentralID PMC6173097

  • Improvements of Procedural Results With a New-Generation Self-Expanding Transfemoral Aortic Valve Prosthesis in Comparison to the Old-Generation Device JOURNAL OF INTERVENTIONAL CARDIOLOGY Gomes, B., Geis, N. A., Chorianopoulos, E., Meder, B., Leuschner, F., Katus, H. A., Bekeredjian, R. 2017; 30 (1): 72-78

    Abstract

    In this study, we compare procedural results of our first Evolut R (Medtronic, Minneapolis, MN, USA) implantations with the last CoreValve implantations. Main endpoints include paravalvular regurgitation, major vascular complications, stroke, and pacemaker implantation.The evolution of transcatheter aortic valve replacement (TAVR) was possible due to various technical improvements, leading to better periprocedural and long-term outcome. The newly designed Evolut R valve has the potential to further improve TAVR's performance.We retrospectively analyzed our first 100 consecutive patients who received the Evolut R valve with the last 100 consecutive patients who received the CoreValve prosthesis between July 2013 and February 2016. Only patients treated with a 26 mm or 29 mm bioprosthesis were included.No significant differences in patient characteristics were noticed. Both angiography and echocardiography after TAVR showed significantly higher rates of "none or trace" regurgitation in the Evolut R group (angiography: 67% Evolut R vs. 29.3% CoreValve; P < 0.001; echocardiography: 68% Evolut R vs. 46.5% CoreValve; P < 0.05). No significant differences were seen in 30-day mortality (7% CoreValve vs. 1% Evolut R), stroke rates (3% CoreValve vs. 2% Evolut R), pacemaker implantation rates (24% CoreValve vs. 23% Evolut R), and major vascular complications (6% CoreValve vs. 1% Evolut R). Implantations were significantly higher with the Evolut R prosthesis.TAVR with the new Evolut R resulted in significantly lower paravalvular regurgitation. This may be due to redesigned cell geometry and higher precision during implantations, as well as the ability to resheath a malpositioned valve.

    View details for DOI 10.1111/joic.12356

    View details for Web of Science ID 000394663500009

    View details for PubMedID 27882613

  • Repositionable self-expanding aortic bioprosthesis EXPERT REVIEW OF MEDICAL DEVICES Gomes, B., Katus, H. A., Bekeredjian, R. 2017; 14 (7): 565-576

    Abstract

    Transcatheter aortic valve implantation/replacement (TAVI or TAVR) has been established as a first line therapy in patients with symptomatic severe aortic stenosis (AS) at high or prohibitive surgical risk and as an alternative in elderly patients with intermediate surgical risk. Since its first-in-human procedure in 2002, the past 15-years have shown rapid developments in TAVI technology with the introduction and further improvement of new transcatheter heart valves (THV). Areas covered: There are currently several THV systems available, based on balloon-expandable, self-expandable or other technologies. Some of these are repositionable and retrievable even after partial or full deployment, potentially reducing the risk of malpositioning. The aim of this review is to describe such repositionable self-expandable THV systems. Expert commentary: Repositionability potentially represents a crucial step towards higher safety and efficacy of TAVI. It is unclear if full self-expandability or a combination of self and mechanical expansion will be more advantageous.

    View details for DOI 10.1080/17434440.2017.1338136

    View details for Web of Science ID 000405699700007

    View details for PubMedID 28571486