Publications by authors named "Aniela Petrescu"

22 Publications

  • Page 1 of 1

Outcomes Stratified by Adapted Inclusion Criteria After Mitral Edge-to-Edge Repair.

J Am Coll Cardiol 2021 12;78(24):2408-2421

Department of Cardiology, University Heart and Vascular Center Hamburg, Germany; German Center for Cardiovascular Research, Partner Site Hamburg/Lübeck/Kiel, Germany. Electronic address:

Background: Although mitral valve transcatheter edge-to-edge repair (M-TEER) achieves symptomatic benefit for a broad spectrum of patients with relevant secondary mitral regurgitation, conflicting data exist on its prognostic impact.

Objectives: Adapted enrollment criteria approaching those used in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) and MITRA-FR (Percutaneous Repair or Medical Treatment for Secondary Mitral Regurgitation) trials were retrospectively applied to a European real-world registry to evaluate the influence of the respective criteria on outcomes.

Methods: A total of 1,022 patients included in the EuroSMR (European Registry of Transcatheter Repair for Secondary Mitral Regurgitation) registry and treated with M-TEER (November 2008 to September 2019) were stratified into COAPT-eligible (n = 353 [34.5%]) and COAPT-ineligible (n = 669 [65.5%]) as well as MITRA-FR-eligible (n = 408 [48.3%]) and MITRA-FR-ineligible (n = 437 [51.7%]) groups.

Results: Although the stratification of patients according to adapted MITRA-FR criteria led to comparable outcomes regarding all-cause mortality (P = 0.19), the application of adapted COAPT enrollment criteria demonstrated lower mortality rates in COAPT-eligible compared with COAPT-ineligible patients (P < 0.001). Multivariable Cox regression analysis identified New York Heart Association functional class IV (hazard ratio [HR]: 2.29; 95% confidence interval [CI]: 1.53-3.42; P < 0.001), logarithmic N-terminal pro-brain natriuretic peptide (HR: 1.47; 95% CI: 1.24-1.75; P < 0.001), and right ventricular-to-pulmonary arterial coupling (HR: 0.10; 95% CI: 0.02-0.57; P = 0.009) as independent predictors of outcome. Yet improvement of functional outcome was demonstrated in a subset of patients irrespective of COAPT eligibility status.

Conclusions: In this real-world cohort of patients with secondary mitral regurgitation undergoing M-TEER, the retrospective application of adapted COAPT enrollment criteria successfully identified a specific phenotype demonstrating lower mortality rates. On the contrary, stratification according to adapted MITRA-FR criteria resulted in comparable outcomes.
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http://dx.doi.org/10.1016/j.jacc.2021.10.011DOI Listing
December 2021

Effectiveness of a Real-Time X-ray Dosimetry Monitor in Reducing Radiation Exposure in Coronary Procedures: The ESPRESSO-Raysafe Randomized Trial.

J Clin Med 2021 Nov 17;10(22). Epub 2021 Nov 17.

Department of Cardiology, Cardiology 1, University Medical Center Mainz and Deutsches Zentrum für Herz und Kreislauf Forschung, Standort Rhein-Main, 55131 Mainz, Germany.

Background-Several methods to reduce radiation exposure in the setting of coronary procedures are available on the market, and we previously showed that additional radiation shields reduce operator exposure during radial interventions. We set out to examine the efficacy of real-time personal dosimetry monitoring in a real-world setting of radial artery catheterization. Methods and Results-In an all-comer prospective, parallel study, consecutive coronary diagnostic and intervention procedures were performed with the use of standard radiation shield alone (control group) or with the addition of a real-time dosimetry monitoring system (Raysafe, Billdal, Sweden, monitoring group). The primary outcome was the difference in exposure of the primary operator among groups. Additional endpoints included patient, nurse, second operator exposure and fluoroscopy time. A total of 700 procedures were included in the analysis ( = 369 in the monitoring group). There were no differences among groups in patients' body mass index ( = 0.232), type of procedure (intervention vs. diagnostic, = 0.172), and patient sex ( = 0.784). Fluoroscopy time was shorter in the monitoring group (5.6 (5.1-6.2) min vs. 7.0 (6.1-7.7) min, = 0.023). Radiation exposure was significantly lower in the monitoring group for the patient (135 (115-151) µSv vs. 208 (176-245) µSv, < 0.0001) but not for the first operator (9 (7-11) µSv vs. 10 (8-11), = 0.70) and the assistant (2 (1-2) µSv vs. 2 (1-2) µSv, = 0.121). Conclusions-In clinical daily practice, the use of a real-time dosimetry monitoring device reduces patient radiation exposure and fluoroscopy time without an effect on operator radiation exposure.
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http://dx.doi.org/10.3390/jcm10225350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8621135PMC
November 2021

Left Atrial Strain Determinants During the Cardiac Phases.

JACC Cardiovasc Imaging 2021 Oct 7. Epub 2021 Oct 7.

Department of Cardiovascular Sciences, Catholic University of Leuven, Leuven, Belgium; Department of Cardiovascular Diseases, University Hospitals Leuven, Leuven, Belgium. Electronic address:

Objectives: The present study investigated the determinants of left atrial (LA) strain in all phases of the cardiac cycle.

Background: LA strain by speckle-tracking echocardiography allows the assessment of LA function in each phase of the cardiac cycle. However, its determinants and its relation with left ventricular (LV) function have not yet been fully described.

Methods: The authors performed a retrospective analysis in 127 patients with different cardiovascular pathologies. Using 2-dimensional speckle tracking in 4- and 2-chamber apical views we derived both LA and LV strain curves. Strain-strain loops were reconstructed using LV strain and the corresponding, synchronized LA strain data. Linear regressions were calculated for the entire strain-strain loop as well as for the 3 phases of the cardiac cycle (systole, and early and late diastole). The association between LA strain parameters and LV systolic and diastolic parameters was studied. The prediction of cardiovascular events was evaluated for both measured and predicted LA strain and other parameters.

Results: LA and LV strain curves presented excellent correlations with an R >0.9 for the cardiac cycle, and >0.97 for its phases. Moreover, the ratios of LV/LA maximal volumes and the slopes of the LA-LV strain-strain loops of the individual patients correlated well (R = 0.75). In each phase of the cardiac cycle, LA strain parameters correlated well with the corresponding LV strain and the LV-LA volume ratio (R >0.78). No significant difference in predictive ability of cardiovascular events or atrial fibrillation between the measured and predicted LA strain was observed (P > 0.05 for both).

Conclusions: In the absence of abnormal LA/LV volume exchange, LA strain is, to a large extent, determined by LV strain and further modulated by the ratio of LV and LA volumes. Nonetheless, measuring LA strain is of high clinical interest because it integrates several parameters into a single, robust, and reproducible measurement.
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http://dx.doi.org/10.1016/j.jcmg.2021.09.009DOI Listing
October 2021

Early symptomatic benefit indicates long-term prognosis after transcatheter mitral valve edge-to-edge repair in functional and degenerative etiology.

Int J Cardiol 2021 Dec 23;344:141-146. Epub 2021 Sep 23.

Department of Cardiology, Cardiology I, University Medical Center Mainz (Johannes Gutenberg-University Mainz), Mainz, Germany. Electronic address:

Background: Mitral regurgitation (MR) is common in patients with heart failure and constitutes an independent risk factor for adverse prognosis besides NYHA-class. The predictive value of dyspnea reduction after transcatheter mitral valve repair (TMVr) on outcome has not been investigated up to now.

Methods And Results: We enrolled 627 consecutive patients (47.0% female, 57.4% functional MR; median follow-up 486 days[IQR 157/961]; survival status available in 96.8%; symptoms assessed in n = 556 at baseline / n = 406 at 1 month) treated with isolated percutaneous mitral valve edge-to-edge repair in our center from 06/2010-03/2018 (exclusion of combined forms of TMVr) in a monocentric retrospective analysis. Survival was 97.6% at discharge, 73.9% after 1, 54.5% after 3, 37.6% after 5 and 21.7% after 7-years. Before TMVr, NYHA-classes III/IV were found in 89.0%. Of these, 74.7% reported symptomatic relief (reduction in NYHA-class) one month after procedure (NYHA class recorded in 406 patients at 30 days). NYHA-classes III/IV were documented in 37.2% (p < 0.001) at 30 days and in 36.6% (p < 0.001) at 1 year without significant changes between the follow-ups. Dyspnea reduction was accompanied by significantly improved long-term survival (1 year, 89.1 vs 71.2%, p = 0.001, 2 years: 75.5 vs 58.7%, p = 0.039) and was identified as an independent predictor for lower mortality (1-year HR for increased mortality by missing symptomatic improvement 2.94 [95%CI 1.53-5.65], p = 0.001; long-term HR 1.95 [95%CI 1.29-2.94], p = 0.001) independently in both etiologies of MR.

Conclusion: TMVr by edge-to-edge therapy enables early and sustainable symptomatic improvement in nearly 75% of the symptomatic patients. The simple assessment of postinterventional changes in NYHA-class might serve as an independent predictor for mid- and long-term prognosis in both FMR and DMR.
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http://dx.doi.org/10.1016/j.ijcard.2021.09.038DOI Listing
December 2021

Right/Left Ventricular Blood Pool T2 Ratio as an Innovative Cardiac MRI Screening Tool for the Identification of Left-to-Right Shunts in Patients With Right Ventricular Disease.

J Magn Reson Imaging 2021 Aug 10. Epub 2021 Aug 10.

Department of Imaging, Advanced Cardiovascular Imaging Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

Background: Left-to-right (L-R) shunts are characterized by a pathological connection between high- and low-pressure systems, leading to a mixing of oxygen-rich blood with low oxygenated blood. They are typically diagnosed by phase-contrast cardiac magnetic resonance imaging (MRI) which requires extensive planning. T2 is sensitive to blood oxygenation and may be able to detect oxygenation differences between the left (LV) and right ventricles (RV) caused by L-R shunts.

Purpose: To test the feasibility of routine T2 mapping to detect L-R shunts.

Study Type: Retrospective.

Population: Patients with known L-R shunts (N = 27), patients with RV disease without L-R shunts (N = 21), and healthy volunteers (HV; N = 52).

Field Strength/sequence: 1.5 and 3 T/balanced steady-state free-precession (bSSFP) sequence (cine imaging), T2-prepared bSSFP sequence (T2 mapping), and velocity sensitized gradient echo sequence (phase-contrast MRI).

Assessment: Aortic (Qs) and pulmonary (Qp) flow was measured by phase-contrast imaging, and the Qp/Qs ratio was calculated as a measure of shunt severity. T2 maps were used to measure T2 in the RV and LV and the RV/LV T2 ratio was calculated. Cine imaging was used to calculate RV end-diastolic volume index (RV-EDVi).

Statistical Tests: Wilcoxon test, paired t-tests, Spearmen correlation coefficient, receiver operating curve (ROC) analysis. Significance level P < 0.05.

Results: The Qp/Qs and T2 ratios in L-R shunt patients (1.84 ± 0.84 and 0.89 ± 0.07) were significantly higher compared to those in patients with RV disease (1.01 ± 0.03 and 0.72 ± 0.10) and in HV (1.04 ± 0.04 and 0.71 ± 0.09). A T2 ratio of >0.78 showed a sensitivity, specificity, and negative predictive value of 100%, 73.9%, and 100%, respectively, for the detection of L-R shunts. The T2 ratio was strongly correlated with the severity of the shunt (r = 0.83).

Data Conclusion: RV/LV T2 ratio is an imaging biomarker that may be able to detect or rule-out L-R shunts. Such a diagnostic tool may prevent unnecessary phase-contrast acquisitions in cases with RV dilatation of unknown etiology.

Level Of Evidence: 3 TECHNICAL EFFICACY: Stage 2.
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http://dx.doi.org/10.1002/jmri.27881DOI Listing
August 2021

Impact of Residual Mitral Regurgitation on Survival After Transcatheter Edge-to-Edge Repair for Secondary Mitral Regurgitation.

JACC Cardiovasc Interv 2021 06 12;14(11):1243-1253. Epub 2021 May 12.

Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Munich, Germany; Munich Heart Alliance, Partner Site German Center for Cardiovascular Disease, Munich, Germany. Electronic address:

Objectives: The aim of this study was to assess the impact of residual mitral regurgitation (resMR) on mortality with respect to left ventricular dilatation (LV-Dil) or right ventricular dysfunction (RV-Dys) in patients with secondary mitral regurgitation (SMR) who underwent mitral valve transcatheter edge-to-edge repair (TEER).

Background: The presence of LV-Dil and RV-Dys correlates with advanced stages of heart failure in SMR patients, which may impact the outcome after TEER.

Methods: SMR patients in a European multicenter registry were evaluated. Investigated outcomes were 2-year all-cause mortality and improvement in New York Heart Association functional class with respect to MR reduction, LV-Dil (defined as LV end-diastolic volume ≥159 ml), and RV-Dys (defined as tricuspid annular plane systolic excursion-to-systolic pulmonary artery pressure ratio of <0.274 mm/mm Hg).

Results: Among 809 included patients, resMR ≤1+ was achieved in 546 (67%) patients. Overall estimated 2-year mortality rate was 32%. Post-procedural resMR was significantly associated with mortality (p = 0.031). Although the improvement in New York Heart Association functional class persisted regardless of either LV-Dil or RV-Dys, the beneficial treatment effect of resMR ≤1+ on 2-year mortality was observed only in patients without LV-Dil and RV-Dys (hazard ratio: 1.75; 95% confidence interval: 1.03 to 3.00).

Conclusions: Achieving optimal MR reduction by TEER is associated with improved survival in SMR patients, especially if the progress in heart failure is not too advanced. In SMR patients with advanced stages of heart failure, as evidenced by LV-Dil or RV-Dys, the treatment effect of TEER on symptomatic improvement is maintained, but the survival benefit appears to be reduced.
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http://dx.doi.org/10.1016/j.jcin.2021.03.050DOI Listing
June 2021

Sex-Related Clinical Characteristics and Outcomes of Patients Undergoing Transcatheter Edge-to-Edge Repair for Secondary Mitral Regurgitation.

JACC Cardiovasc Interv 2021 04 31;14(8):819-827. Epub 2021 Mar 31.

Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Munich, Germany; Munich Heart Alliance, Partner Site German Center for Cardiovascular Disease (DZHK), Munich, Germany. Electronic address:

Objectives: The authors sought to assess sex-based differences in characteristics and outcomes of patients undergoing transcatheter edge-to-edge mitral valve repair (TMVR) for secondary mitral regurgitation (SMR).

Background: Subgroup analysis from the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial indicated potential sex-related differences in outcomes after TMVR. The impact of sex on results after TMVR in a real-world setting is unknown.

Methods: The authors assessed clinical outcomes and echocardiographic parameters in women and men undergoing TMVR for SMR between 2008 and 2018 who were included in the large, international, multicenter real-world EuroSMR registry (European Registry of Transcatheter Repair for Secondary Mitral Regurgitation).

Results: A total of 1,233 patients, including 445 women (36%) and 788 men (64%), were analyzed. Although women were significantly older and had fewer comorbidities than men, TMVR was equally effective in women and men (mitral regurgitation [MR] grade ≤2+ at discharge: 93.2% vs. 94.6% for women vs. men; p = 0.35). All-cause mortality at 1 year (17.9% vs. 18.9%, adjusted hazard ratio: 0.806; p = 0.46) and at 2-year follow-up (26.5% vs. 26.4%, adjusted hazard ratio: 0.757; p = 0.26) were similar in women versus men after multivariate regression analysis. Durability of MR reduction, improvement in symptoms, quality of life, and functional capacity did also not differ during follow-up.

Conclusions: Results from the EuroSMR registry confirmed effective and similar MR reduction with TMVR in women and men. There were no sex-related differences in clinical outcomes up to 2 years of follow-up.
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http://dx.doi.org/10.1016/j.jcin.2020.12.042DOI Listing
April 2021

Impact of effective regurgitant orifice area on outcome of secondary mitral regurgitation transcatheter repair.

Clin Res Cardiol 2021 May 4;110(5):732-739. Epub 2021 Mar 4.

Medizinische Klinik und Poliklinik I, Ludwig Maximilians Universität München, Munich, Germany.

Objectives: To assess the value of effective regurgitant orifice (ERO) in predicting outcome after edge-to-edge transcatheter mitral valve repair (TMVR) for secondary mitral regurgitation (SMR) and identify the optimal cut-off for patients' selection.

Methods: Using the EuroSMR (European Registry of Transcatheter Repair for Secondary Mitral Regurgitation) registry, that included patients undergoing edge-to-edge TMVR for SMR between November 2008 and January 2019 in 8 experienced European centres, we assessed the optimal ERO threshold associated with mortality in SMR patients undergoing TMVR, and compared characteristics and outcomes of patients according to baseline ERO.

Results: Among 1062 patients with severe SMR and ERO quantification by proximal isovelocity surface area method in the registry, ERO was < 0.3 cm in 575 patients (54.1%), who were more symptomatic at baseline (NYHA class ≥ III: 91.4% vs. 86.9%, for ERO < vs. ≥ 0.3 cm; P = 0.004). There was no difference in all-cause mortality at 2-year follow-up according to baseline ERO (28.3% vs. 30.0% for ERO < vs. ≥ 0.3 cm, P = 0.585). Both patient groups demonstrated significant improvement of at least one NYHA class (61.7% and 73.8%, P = 0.002), resulting in a prevalence of NYHA class ≤ II at 1-year follow-up of 60.0% and 67.4% for ERO < vs. ≥ 0.3 cm, respectively (P = 0.05).

Conclusion: All-cause mortality at 2 years after TMVR does not differ if baseline ERO is < or ≥ 0.3 cm, and both groups exhibit relevant clinical improvements. Accordingly, TMVR should not be withheld from patients with ERO < 0.3 cm who remain symptomatic despite optimal medical treatment, if TMVR appropriateness was determined by experienced teams in dedicated valve centres.
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http://dx.doi.org/10.1007/s00392-021-01807-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099828PMC
May 2021

Impact of Right Ventricular Dysfunction on Outcomes After Transcatheter Edge-to-Edge Repair for Secondary Mitral Regurgitation.

JACC Cardiovasc Imaging 2021 04 10;14(4):768-778. Epub 2021 Feb 10.

Department of Cardiology, Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Munich, Germany; Munich Heart Alliance, Partner Site, German Center for Cardiovascular Disease, Munich, Germany. Electronic address:

Objectives: This study sought to assess the impact of right ventricular dysfunction (RVD) as defined by impaired right ventricular-to-pulmonary artery (RV-PA) coupling, on survival after edge-to-edge transcatheter mitral valve repair (TMVR) for severe secondary mitral regurgitation (SMR).

Background: Conflicting data exist regarding the benefit of TMVR in severe SMR. A possible explanation could be differences in RVD.

Methods: Using data from the EuroSMR (European Registry on Outcomes in Secondary Mitral Regurgitation) registry, this study compared the characteristics and outcomes of SMR patients undergoing TMVR, according to their RV-PA coupling, assessed by tricuspid annular plane systolic excursion-to-systolic pulmonary artery pressure (TAPSE/sPAP) ratio.

Results: Overall, 817 patients with severe SMR and available RV-PA coupling assessment underwent TMVR in the participating centers. RVD was present in 211 patients (25.8% with a TAPSE/sPAP ratio <0.274 mm/mm Hg). Although all patients demonstrated significant improvement in their New York Heart Association (NYHA) functional class, there was a trend toward a lower rate of NYHA functional class I or II among patients with RVD (56.5% vs. 65.5%, respectively; p = 0.086) after TMVR. Survival rates at 1 and 2 years were lower among patients with RVD (70.2% vs. 84.0%, respectively; p < 0.001; and 53.4% vs. 73.1%, respectively; p < 0.001). On multivariate analysis, a reduced TAPSE/sPAP ratio was a strong predictor of mortality (odds ratio: 1.62; 95% confidence interval: 1.14 to 2.31; p = 0.007).

Conclusions: RVD, as shown by impairment of RV-PA coupling, is a major predictor of adverse outcome in patients undergoing TMVR for severe SMR. The often neglected functional and anatomic RV parameters should be systematically assessed when planning TMVR procedures for patients with severe SMR.
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http://dx.doi.org/10.1016/j.jcmg.2020.12.015DOI Listing
April 2021

Concepts and applications of ultrafast cardiac ultrasound imaging.

Echocardiography 2021 01 20;38(1):7-15. Epub 2021 Jan 20.

Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.

The concept of ultrafast echocardiographic imaging has been around for decades. However, only recent progress in ultrasound machine hardware and computer technology allowed to apply this concept to echocardiography. High frame rate echocardiography can visualize phenomena that have never been captured before. It enables a wide variety of potential new applications, including shear wave imaging, speckle tracking, ultrafast Doppler imaging, and myocardial perfusion imaging. The principles of these applications and their potential clinical use will be presented in this manuscript.
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http://dx.doi.org/10.1111/echo.14971DOI Listing
January 2021

Concomitant tricuspid regurgitation severity and its secondary reduction determine long-term prognosis after transcatheter mitral valve edge-to-edge repair.

Clin Res Cardiol 2021 May 12;110(5):676-688. Epub 2021 Jan 12.

Department of Cardiology, Cardiology I, University Medical Center Mainz (Johannes Gutenberg-University Mainz), Mainz, Germany.

Background: Concomitant tricuspid regurgitation (TR) is a common finding in mitral regurgitation (MR). Transcatheter repair (TMVR) is a favorable treatment option in patients at elevated surgical risk. To date, evidence on long-term prognosis and the prognostic impact of TR after TMVR is limited.

Methods: Long-term survival data of patients undergoing isolated edge-to-edge repair from June 2010 to March 2018 (combinations with other forms of TMVR or tricuspid valve therapy excluded) were analyzed in a retrospective monocentric study. TR severity was categorized and the impact of TR on survival was analysed.

Results: Overall, 606 patients [46.5% female, 56.4% functional MR (FMR)] were enrolled in this study. TR at baseline was categorized severe/medium/mild/no or trace in 23.2/34.3/36.3/6.3% of the cases. At 30-day follow-up, improvement of at least one TR-grade was documented in 34.9%. Severe TR at baseline was identified as predictor of 1-year survival [65.2% vs. 77.0%, p = 0.030; HR for death 1.68 (95% CI 1.12-2.54), p = 0.013] and in FMR-patients also regarding long-term prognosis [adjusted HR for long-term mortality 1.57 (95% CI 1.00-2.45), p = 0.049]. Missing post-interventional reduction of TR severity was predictive for poor prognosis, especially in the FMR-subgroup [1-year survival: 92.9% vs. 78.3%, p = 0.025; HR for death at 1-year follow-up 3.31 (95% CI 1.15-9.58), p = 0.027]. While BNP levels decreased in both subgroups, TR reduction was associated with improved symptomatic benefit (NYHA-class-reduction 78.6 vs. 65.9%, p = 0.021).

Conclusion: In this large study, both, severe TR at baseline as well as missing secondary reduction were predictive for impaired long-term prognosis, especially in patients with FMR etiology. TR reduction was associated with increased symptomatic benefit.
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http://dx.doi.org/10.1007/s00392-020-01798-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099767PMC
May 2021

Shear Wave Elastography Using High-Frame-Rate Imaging in the Follow-Up of Heart Transplantation Recipients.

JACC Cardiovasc Imaging 2020 11 28;13(11):2304-2313. Epub 2020 Sep 28.

Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium; Department of Cardiovascular Diseases, University Hospitals Leuven, Leuven, Belgium. Electronic address:

Objectives: The purpose of this study was to investigate whether propagation velocities of naturally occurring shear waves (SWs) at mitral valve closure (MVC) increase with the degree of diffuse myocardial injury (DMI) and with invasively determined LV filling pressures as a reflection of an increase in myocardial stiffness in heart transplantation (HTx) recipients.

Background: After orthotopic HTx, allografts undergo DMI that contributes to functional impairment, especially to increased passive myocardial stiffness, which is an important pathophysiological determinant of left ventricular (LV) diastolic dysfunction. Echocardiographic SW elastography is an emerging approach for measuring myocardial stiffness in vivo. Natural SWs occur after mechanical excitation of the myocardium, for example, after MVC, and their propagation velocity is directly related to myocardial stiffness, thus providing an opportunity to assess myocardial stiffness at end-diastole.

Methods: A total of 52 HTx recipients who underwent right heart catheterization (all) and cardiac magnetic resonance (CMR) (n = 23) during their annual check-up were prospectively enrolled. Echocardiographic SW elastography was performed in parasternal long axis views of the LV using an experimental scanner at 1,135 ± 270 frames per second. The degree of DMI was quantified with T1 mapping.

Results: SW velocity at MVC correlated best with native myocardial T1 values (r = 0.75; p < 0.0001) and was the best noninvasive parameter that correlated with pulmonary capillary wedge pressures (PCWP) (r = 0.54; p < 0.001). Standard echocardiographic parameters of LV diastolic function correlated poorly with both native T1 and PCWP values.

Conclusions: End-diastolic SW propagation velocities, as measure of myocardial stiffness, showed a good correlation with CMR-defined diffuse myocardial injury and with invasively determined LV filling pressures in patients with HTx. Thus, these findings suggest that SW elastography has the potential to become a valuable noninvasive method for the assessment of diastolic myocardial properties in HTx recipients.
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http://dx.doi.org/10.1016/j.jcmg.2020.06.043DOI Listing
November 2020

Impact of Proportionality of Secondary Mitral Regurgitation on Outcome After Transcatheter Mitral Valve Repair.

JACC Cardiovasc Imaging 2021 04 26;14(4):715-725. Epub 2020 Aug 26.

Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Munich, Germany; Munich Heart Alliance, Partner Site German Center for Cardiovascular Disease, Munich, Germany. Electronic address:

Objectives: The purpose of this paper was to evaluate the impact of proportionality of secondary mitral regurgitation (SMR) in a large real-world registry of transcatheter edge-to-edge mitral valve repair (TMVr) BACKGROUND: Differences in the outcomes of recent randomized trials of TMVr for SMR may be explained by the proportionality of SMR severity to left ventricular (LV) volume.

Methods: The ratio of pre-procedural effective regurgitant orifice area (EROA) to LV end-diastolic volume (LVEDV) was retrospectively assessed in patients undergoing TMVr for severe SMR between 2008 and 2019 from the EuroSMR registry. A recently proposed SMR proportionality scheme was adapted to stratify patients according to EROA/LVEDV ratio in 3 groups: MR-dominant (MD), MR-LV-co-dominant (MLCD), and LV-dominant (LD). All-cause mortality was assessed as a primary outcome, secondary heart failure (HF) outcomes included hospitalization for HF (HHF), New York Heart Association (NYHA) functional class, N-terminal pro-B-type natriuretic peptide (NT-proBNP), 6-min-walk distance, quality of life and MR grade.

Results: A total of 1,016 patients with an EROA/LVEDV ratio were followed for 22 months after TMVr. MR was reduced to grade ≤2+ in 92%, 96%, and 94% of patients (for MD, MLCD, and LD, respectively; p = 0.18). After adjustment for covariates including age, sex, diabetes, kidney function, body surface area, LV ejection fraction, and procedural MR reduction (grade ≤2+), adjusted rates of 2-year mortality in MD patients did not differ from those for MLCD patients (17% vs. 18%, respectively), whereas it was higher in LD patients (23%; p = 0.02 for comparison vs. MD+MLCD). The adjusted first HHF rate differed between groups (44% in MD, 56% in MLCD, 29% in LD; p = 0.01) as did the adjusted time for first death or HHF rate (66% in MD, 82% in MLCD, 68% in LD; p = 0.02). Improvement of NYHA functional class was seen in all groups (p < 0.001). Values for 6-min-walk distances, quality of life and NT-proBNP improved in most patients.

Conclusions: MD and MLCD patients had a comparable, adjusted 2-year mortality rate after TMVr which was slightly better than that of LD patients. Patients treated with TMVr had symptomatic improvement regardless of EROA/LVEDV ratio.
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http://dx.doi.org/10.1016/j.jcmg.2020.05.042DOI Listing
April 2021

A Novel 2-D Speckle Tracking Method for High-Frame-Rate Echocardiography.

IEEE Trans Ultrason Ferroelectr Freq Control 2020 09 3;67(9):1764-1775. Epub 2020 Apr 3.

Speckle tracking echocardiography (STE) is a clinical tool to noninvasively assess regional myocardial function through the quantification of regional motion and deformation. Even if the time resolution of STE can be improved by high-frame-rate (HFR) imaging, dedicated HFR STE algorithms have to be developed to detect very small interframe motions. Therefore, in this article, we propose a novel 2-D STE method, purposely developed for HFR echocardiography. The 2-D motion estimator consists of a two-step algorithm based on the 1-D cross correlations to separately estimate the axial and lateral displacements. The method was first optimized and validated on simulated data giving an accuracy of ~3.3% and ~10.5% for the axial and lateral estimates, respectively. Then, it was preliminarily tested in vivo on ten healthy volunteers showing its clinical applicability and feasibility. Moreover, the extracted clinical markers were in the same range as those reported in the literature. Also, the estimated peak global longitudinal strain was compared with that measured with a clinical scanner showing good correlation and negligible differences (-20.94% versus -20.31%, p -value = 0.44). In conclusion, a novel algorithm for STE was developed: the radio frequency (RF) signals were preferred for the axial motion estimation, while envelope data were preferred for the lateral motion. Furthermore, using 2-D kernels, even for 1-D cross correlation, makes the method less sensitive to noise.
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http://dx.doi.org/10.1109/TUFFC.2020.2985451DOI Listing
September 2020

Interplay of cardiac remodelling and myocardial stiffness in hypertensive heart disease: a shear wave imaging study using high-frame rate echocardiography.

Eur Heart J Cardiovasc Imaging 2020 06;21(6):664-672

Department of Cardiovascular Sciences, University of Leuven, Herestraat 49, 3000 Leuven, Belgium.

Aims: To determine myocardial stiffness by means of measuring the velocity of naturally occurring myocardial shear waves (SWs) at mitral valve closure (MVC) and investigate their changes with myocardial remodelling in patients with hypertensive heart disease.

Methods And Results: Thirty-three treated arterial hypertension (HT) patients with hypertrophic left ventricular (LV) remodelling (59 ± 14 years, 55% male) and 26 aged matched healthy controls (55±15 years, 77% male) were included. HT patients were further divided into a concentric remodelling (HT1) group (13 patients) and a concentric hypertrophy (HT2) group (20 patients). LV parasternal long-axis views were acquired with an experimental ultrasound scanner at 1266 ± 317 frames per seconds. The SW velocity induced by MVC was measured from myocardial acceleration maps. SW velocities differed significantly between HT patients and controls (5.83 ± 1.20 m/s vs. 4.04 ± 0.96 m/s; P < 0.001). In addition, the HT2 group had the highest SW velocities (P < 0.001), whereas values between controls and the HT1 group were comparable (P = 0.075). Significant positive correlations were found between SW velocity and LV remodelling (interventricular septum thickness: r = 0.786, P < 0.001; LV mass index: r = 0.761, P < 0.001). SW velocity normalized for wall stress indicated that myocardial stiffness in the HT2 group was twice as high as in controls (P < 0.001), whereas values of the HT1 group overlapped with the controls (P = 1.00).

Conclusions: SW velocity as measure of myocardial stiffness is higher in HT patients compared with healthy controls, particularly in advanced hypertensive heart disease. Patients with concentric remodelling have still normal myocardial properties whereas patients with concentric hypertrophy show significant stiffening.
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http://dx.doi.org/10.1093/ehjci/jez205DOI Listing
June 2020

How Does Regional Hypertrophy Affect Strain Measurements With Different Speckle-Tracking Methods?

J Am Soc Echocardiogr 2019 11 31;32(11):1444-1450. Epub 2019 Jul 31.

Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium. Electronic address:

Background: In this study, we evaluate the impact of abnormal myocardial shapes, such as regional hypertrophy, on longitudinal strain measurements with different tracking approaches.

Methods: We selected 40 patients with normal ejection fraction and prominent septal bulge. We assessed longitudinal strain with full wall (FW) tracking, (GE EchoPAC) as well as endo-, mid-, and epicardial (EME) tracking (Tomtec ImageArena), on the same image acquired with a GE machine (using raw data and full frame rate DICOM data, respectively). We used a region of interest (ROI) which follows precisely the endo- and epicardial contours (true contour ROI) and one where the bulging region was excluded (straight ROI).

Results: In segments with bulge, absolute segmental longitudinal strain values were in all myocardial layers significantly higher with a straight ROI compared to a true contour ROI, both with FW tracking and EME tracking. The highest difference was found in the endocardial layer (3.4 ± 2.5% and 7.7 ± 7.1%, respectively, both P < 0.001). In the bulged segments, the effect of ROI shape was more pronounced in EME tracking software compared to FW tracking software. Bulged segments also influenced global longitudinal strain measurements, mostly in the endocardial layer (P < 0.001). Global longitudinal strain values obtained with the straight ROI correlated better with longitudinal fractional shortening of the LV.

Conclusions: Regional bulging has a significant effect on both global and segmental strain measurements. Endocardial strain values obtained with EME tracking and a true contour ROI were most sensitive to bulging. Midwall strain values derived from FW tracking using a straight ROI were most robust.
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http://dx.doi.org/10.1016/j.echo.2019.06.008DOI Listing
November 2019

Velocities of Naturally Occurring Myocardial Shear Waves Increase With Age and in Cardiac Amyloidosis.

JACC Cardiovasc Imaging 2019 12 13;12(12):2389-2398. Epub 2019 Feb 13.

Department of Cardiovascular Science, Division of Cardiology, University Hospital Leuven, University of Leuven, Leuven, Belgium. Electronic address:

Objectives: This study sought to evaluate whether velocity of naturally occurring myocardial shear waves (SW) could relate to myocardial stiffness (MS) in vivo.

Background: Cardiac SW imaging has been proposed as a noninvasive tool to assess MS. SWs occur after mechanical excitation of the myocardium (e.g., mitral valve closure [MVC] and aortic valve closure [AVC]), and their propagation velocity is theoretically related to MS, thus providing an opportunity to assess stiffness at end-diastole (ED) and end-systole. However, given that SW propagation in vivo is complex, it remains unclear whether natural SW velocity effectively relates to MS.

Methods: This study prospectively enrolled 50 healthy volunteers (HV) (43.7 ± 17.1 years of age) and 18 patients with cardiac amyloidosis (CA) (68.0 ± 9.8 years of age). HV were divided into 3 age groups: group I, 20 to 39 years of age (n = 24); group II, 40 to 59 years of age (n = 11); and group III, 60 to 80 years of age (n = 15). Parasternal long-axis views were acquired using an experimental scanner. Tissue (Doppler) acceleration maps were extracted from an anatomical M-mode along the midline of the left ventricular septum.

Results: SW propagation velocity was significantly higher in CA patients than in HV after both MVC (3.54 ± 0.93 m/s vs. 6.33 ± 1.63 m/s, respectively; p < 0.001) and AVC (3.75 ± 0.76 m/s vs. 5.63 ± 1.13 m/s, respectively; p < 0.001). Similarly, SW propagation velocity differed significantly among age groups in HV, with a significantly higher value for group III than for group I, both occurring after MVC (p < 0.001) and AVC (p < 0.01). Moreover, SW propagation velocity after MVC was found to be significantly higher in patients with an increasing grade of diastolic dysfunction (p < 0.001). Finally, positive correlation was found between SW velocities after MVC and mitral inflow-to-mitral relaxation velocity ratio (E/E') (r = 0.74; p = 0.002).

Conclusions: End-diastole SW velocities were significantly higher in patients with CA, patients with a higher grade of diastolic dysfunction, and elderly volunteers. These findings thus suggest that the speed of naturally induced SWs may be related to MS.
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http://dx.doi.org/10.1016/j.jcmg.2018.11.029DOI Listing
December 2019

Sex-specific difference in outcome after cardiac resynchronization therapy.

Eur Heart J Cardiovasc Imaging 2019 May;20(5):504-511

Department of Cardiovascular Diseases, University Hospitals Leuven, University of Leuven, Herestraat 49, Leuven, Belgium.

Aims: Observation of better outcome in women after cardiac resynchronization therapy (CRT) has led to controversies about a potential sex-specific response. In this study, we investigated to which extent this sex-specific difference in CRT outcome could be explained by differences in baseline characteristics between both sexes.

Methods And Results: We retrospectively analysed data from a multicentre registry of 1058 patients who received CRT. Patients were examined by echocardiography before and 12 ± 6 months after implantation. Response was defined as ≥15% reduction of left ventricular end-systolic volume at follow-up. Patient's characteristics at baseline, including New York Heart Association class, ejection fraction, QRS width and morphology, ischaemic aetiology of cardiomyopathy (ICM), number of scarred segments, age at implantation, atrial fibrillation, and mechanical dyssynchrony (Dyss) were analysed. Patients were followed for a median duration of 59 months. Primary end point was all-cause mortality. Women (24% of the population) had less ICM (23% vs. 49%, P < 0.0001), less scarred segments (0.4 ± 1.3 vs. 1.0 ± 2.1, P < 0.0001), more left bundle branch block (LBBB; 87% vs. 80%, P = 0.01), and more Dyss at baseline (78% vs. 57%, P < 0.0001). Without matching baseline differences, women showed better survival (log rank P < 0.0001). After matching, survival was similar (log rank P = 0.58). In multivariable analysis, female sex was no independent predictor of neither volumetric response (P = 0.06) nor survival (P = 0.31).

Conclusion: Our data suggest that the repeatedly observed better outcome in women after CRT is mainly due to the lower rate ICM and smaller scars. When comparing patients with similar baseline characteristics, the response of both sexes to CRT is similar.
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http://dx.doi.org/10.1093/ehjci/jey231DOI Listing
May 2019

Natural Shear Wave Imaging in the Human Heart: Normal Values, Feasibility, and Reproducibility.

IEEE Trans Ultrason Ferroelectr Freq Control 2019 03 15;66(3):442-452. Epub 2018 Nov 15.

Left ventricular myocardial stiffness could offer superior quantification of cardiac systolic and diastolic function when compared to the current diagnostic tools. Shear wave elastography in combination with acoustic radiation force has been widely proposed to noninvasively assess tissue stiffness. Interestingly, shear waves can also result from intrinsic cardiac mechanical events (e.g., closure of valves) without the need for external excitation. However, it remains unknown whether these natural shear waves always occur, how reproducible they can be detected and what the normal range of shear wave propagation speed is. The present study, therefore, aimed at establishing the feasibility of detecting shear waves created after mitral valve closure (MVC) and aortic valve closure (AVC), the variability of the measurements, and at reporting the normal values of propagation velocity. Hereto, a group of 30 healthy volunteers was scanned with high-frame rate imaging (>1000 Hz) using an experimental ultrasound system transmitting a diverging wave sequence. Tissue Doppler velocity and acceleration were used to create septal color M-modes, on which the shear waves were tracked and their velocities measured. Overall, the methodology was capable of detecting the transient vibrations that spread throughout the intraventricular septum in response to the closure of the cardiac valves in 92% of the recordings. Reference velocities of 3.2±0.6 m/s at MVC and 3.5±0.6 m/s at AVC were obtained. Moreover, in order to show the diagnostic potential of this approach, two patients (one with cardiac amyloidosis and one undergoing a dobutamine stress echocardiography) were scanned with the same protocol and showed markedly higher propagation speeds: the former presented velocities of 6.6 and 5.6 m/s; the latter revealed normal propagation velocities at baseline, and largely increased during the dobutamine infusion (>15 m/s). Both cases showed values consistent with the expected changes in stiffness and cardiac loading conditions.
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http://dx.doi.org/10.1109/TUFFC.2018.2881493DOI Listing
March 2019

Dual vs single antiplatelet therapy in patients with lower extremity peripheral artery disease - A meta-analysis.

Int J Cardiol 2018 Oct 3;269:292-297. Epub 2018 Jul 3.

INOVA Heart and Vascular Institute, VA, USA; SIRIO MEDICINE research network.

Aims: Peripheral artery disease (PAD) is associated with increased risk of cardiovascular events. The benefits of dual antiplatelet therapy (DAPT) vs single antiplatelet therapy (SAPT) with aspirin in patients with PAD remain subject of ongoing debate.

Methods And Results: We performed a meta-analysis of studies comparing DAPT vs aspirin monotherapy in PAD. Incidence rate ratios (RR) and respective 95% confidence intervals (CI) were used as summary statistics. The primary outcome was mortality. Secondary endpoints were ischemic and bleeding outcomes. Ten studies including 65,675 patients have been included. Compared to SAPT, DAPT was associated with a significant reduction in mortality: RR, 0.89; 95% CI, 0.86-0.92; P < 0.001. Results were consistent across patients with symptomatic PAD and those undergoing bypass or percutaneous transluminal angioplasty (PTA). Similarly, DAPT significantly reduced the risk of repeat peripheral revascularizations (RR, 0.80; 95% CI, 0.69-0.92; P = 0.002). No significant increase of major bleeding complications was observed with DAPT as compared to SAPT (RR, 1.21; 95% CI, 0.87-1.68 P = 0.26).

Conclusions: DAPT, as compared to SAPT, significantly reduces mortality in patients with PAD, with no significant increase in bleeding complications. These findings support DAPT as the mainstay antiplatelet therapeutic regimen in patients with PAD.
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http://dx.doi.org/10.1016/j.ijcard.2018.07.009DOI Listing
October 2018

Role of proprotein convertase subtilisin/kexin type 9 inhibitors in patients with coronary artery disease undergoing percutaneous coronary intervention.

Expert Rev Cardiovasc Ther 2018 Jun 23;16(6):419-429. Epub 2018 May 23.

c Inova Center for Thrombosis Research and Drug Development , Inova Heart and Vascular Institute , Fairfax , VA , USA.

Introduction: Although novel therapies have improved outcomes in PCI patients, a sizeable number of patients still remain at high cardiovascular risk for recurrent event. There is therefore an unmet need for novel therapies that can improve clinical outcomes, with an associated satisfactory safety profile. Proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme is a novel lipid-lowering target with a potential to impact high-cardiovascular risk populations including patients with coronary artery disease (CAD), undergoing the percutaneous coronary intervention (PCI). A number of canonical and non-canonical pathways of PCSK9 action, including inflammation and platelet activation, as well as their inhibition, are undergoing intense investigation. Areas covered: This review will discuss the currently available evidence on PCSK9 inhibitors, pathways of PCSK9 enzyme action and results or its inhibition, the potential role of PCSK9 inhibitors in specific populations undergoing PCI, and completed and ongoing studies in patients with CAD. Expert commentary: PCSK9 inhibitors clinical outcomes in high risk cardiovascular disease patients and have the potential to function as powerful adjunctive therapy in patients undergoing PCI by a twofold mechanism on both lipid lowering and platelet/inflammation pathways.
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http://dx.doi.org/10.1080/14779072.2018.1474099DOI Listing
June 2018

Assessment of the functional diversity of human myoglobin.

Nitric Oxide 2012 May 8;26(4):211-6. Epub 2012 Mar 8.

University Hospital Düsseldorf, Medical Faculty, Division of Cardiology, Pulmonology and Vascular Medicine, Düsseldorf, Germany.

Myoglobin is presumably the most studied protein in biology. Its functional properties as a dioxygen storage and facilitator of dioxygen transport are widely acknowledged. Experimental evidence also implicates an essential role for myoglobin in the heart in regulating nitric oxide homeostasis. Under normoxia, oxygenated myoglobin can scavenge excessive nitric oxide, while under hypoxia, deoxygenated myoglobin can reduce nitrite, an oxidative product of nitric oxide, to bioactive nitric oxide. Myoglobin-driven nitrite reduction can protect the heart from ischemia and reperfusion injury. While horse and mouse myoglobin have been previously described to reduce nitrite under these conditions, a comparable activity has not been detected in human myoglobin. We here show that human myoglobin is a fully functional nitrite reductase. To study the role of human myoglobin for nitric oxide homeostasis we used repeated photometric wavelength scans and chemiluminescence based experiments. The results revealed that oxygenated human myoglobin reacts with nitrite-derived nitric oxide to form ferric myoglobin and that deoxygenated human myoglobin acts as a nitrite reductase in vitro and in situ. Rates of both nitric oxide scavenging and nitrite reduction were significantly higher in human compared to horse myoglobin. These data extend the existing knowledge about the functional properties of human myoglobin and are the basis for further translational studies towards the importance of myoglobin for nitric oxide metabolism in humans.
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http://dx.doi.org/10.1016/j.niox.2012.03.001DOI Listing
May 2012
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