Publications by authors named "Christian Hengstenberg"

315 Publications

Principal Morphomic and Functional Components of Secondary Mitral Regurgitation.

JACC Cardiovasc Imaging 2021 Jul 7. Epub 2021 Jul 7.

Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria. Electronic address:

Objectives: The aim of this work was to identify the key morphological and functional features in secondary mitral regurgitation (sMR) and their prognostic impact on outcome.

Background: Secondary sMR in patients with heart failure and reduced ejection fraction typically results from distortion of the underlying cardiac architecture. The morphological components which may account for the clinical impact of sMR have not been systematically assessed or correlated with clinical outcomes.

Methods: Morphomic and functional network profiling were performed on a cohort of patients with stable heart failure optimized on guideline-based medical therapy. Principal component (PC) analysis and subsequent cluster analysis were used to condense the morphomic and functional data first into PCs with varimax rotation (PC) and second into homogeneous clusters. Clusters and PCs were tested for their correlations with clinical outcomes.

Results: Morphomic and functional data from 383 patients were profiled and subsequently condensed into PCs. PC 1 describes high loadings of left atrial morphological information, and PC 2 describes high loadings of left ventricular (LV) topology. Based on these components, 4 homogeneous clusters were derived. sMR was most prominent in clusters 3 and 4, with the morphological difference being left ventricular size (median end-diastolic volume 188 mL [interquartile range: 160 mL-224 mL] vs 315 mL [264 mL-408 mL]; P < 0.001). Clusters were associated with mortality (P < 0.001), but sMR remained independently associated with mortality after adjusting for the clusters (adjusted HR: 1.42; 95% CI: 1.14-1.77; P < 0.01). The detrimental association of sMR with mortality was mainly driven by cluster 3 (HR: 2.18; 95% CI: 1.32-3.60; P = 0.002), the "small LV cavity" phenotype.

Conclusions: These results challenge the current perceptions that sMR in heart failure with reduced ejection fraction results exclusively from global or local LV remodeling and are suggestive of a potential role of the left atrial component. The association of sMR with mortality cannot be purely attributed to cardiac morphology alone, supporting other complementary key aspects of mitral valve closure consistent with the force balance theory. Unsupervised clustering supports the association of sMR with mortality predominantly driven by the small LV cavity phenotype, as previously suggested by a conceptional framework and termed disproportionate sMR.
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http://dx.doi.org/10.1016/j.jcmg.2021.05.020DOI Listing
July 2021

Burden, treatment use, and outcome of secondary mitral regurgitation across the spectrum of heart failure: observational cohort study.

BMJ 2021 06 30;373:n1421. Epub 2021 Jun 30.

Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria

Objectives: To define prevalence, long term outcome, and treatment standards of secondary mitral regurgitation (sMR) across the heart failure spectrum.

Design: Large scale cohort study.

Setting: Observational cohort study with data from the Viennese community healthcare provider network between 2010 and 2020, Austria.

Participants: 13 223 patients with sMR across all heart failure subtypes.

Main Outcome Measures: Association between sMR and mortality in patients assigned by guideline diagnostic criteria to one of three heart failure subtypes: reduced, mid-range, and preserved ejection fraction, was assessed.

Results: Severe sMR was diagnosed in 1317 patients (10%), correlated with increasing age (P<0.001), occurred across the entire spectrum of heart failure, and was most common in 656 (25%) of 2619 patients with reduced ejection fraction. Mortality of patients with severe sMR was higher than expected for people of the same age and sex in the same community (hazard ratio 7.53; 95% confidence interval 6.83 to 8.30, P<0.001). In comparison with patients with heart failure and no/mild sMR, mortality increased stepwise with a hazard ratio of 1.29 (95% confidence interval 1.20 to 1.38, P<0.001) for moderate and 1.82 (1.64 to 2.02, P<0.001) for severe sMR. The association between severe sMR and excess mortality was consistent after multivariate adjustment and across all heart failure subgroups (mid-range ejection fraction: hazard ratio 2.53 (95% confidence interval 2.00 to 3.19, P<0.001), reduced ejection fraction: 1.70 (1.43 to 2.03, P<0.001), and preserved ejection fraction: 1.52 (1.25 to 1.85, P<0.001)). Despite available state-of-the-art healthcare, high volume heart failure, and valve disease programmes, severe sMR was rarely treated by surgical valve repair (7%) or replacement (5%); low risk transcatheter repair (4%) was similarly seldom used.

Conclusion: Secondary mitral regurgitation is common overall, increasing with age and associated with excess mortality. The association with adverse outcome is significant across the entire heart failure spectrum but most pronounced in those with mid-range and reduced ejection fractions. Despite these poor outcomes, surgical valve repair or replacement are rarely performed; similarly, low risk transcatheter repair, specifically in the heart failure subsets with the highest expected benefit from treatment, is seldom used. The current data suggest an increasing demand for treatment, particularly in view of an expected increase in heart failure in an ageing population.
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http://dx.doi.org/10.1136/bmj.n1421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243241PMC
June 2021

Prognostic Value of Echocardiographic Right Ventricular Function Parameters in the Presence of Severe Tricuspid Regurgitation.

J Clin Med 2021 May 24;10(11). Epub 2021 May 24.

Department of Internal Medicine II, Medical University of Vienna, A-1090 Vienna, Austria.

Background: Presence of severe tricuspid regurgitation (TR) has a significant impact on assessment of right ventricular function (RVF) in transthoracic echocardiography (TTE). High trans-valvular pendulous volume leads to backward-unloading of the right ventricle. Consequently, established cut-offs for normal systolic performance may overestimate true systolic RVF.

Methods: A retrospective analysis was performed entailing all patients who underwent TTE at our institution between 1 January 2013 and 31 December 2016. Only patients with normal left ventricular systolic function and with no other valvular lesion were included. All recorded loops were re-read by one experienced examiner. Patients without severe TR (defined as vena contracta width ≥7 mm) were excluded. All-cause 2-year mortality was chosen as the end-point. The prognostic value of several RVF parameters was tested.

Results: The final cohort consisted of 220 patients, 88/220 (40%) were male. Median age was 69 years (IQR 52-79), all-cause two-year mortality was 29%, median TAPSE was 19 mm (15-22) and median FAC was 42% (30-52). In multivariate analysis, TAPSE with the cutoff 17 mm and FAC with the cutoff 35% revealed non-significant hazard ratios (HR) of 0.75 (95%CI 0.396-1.421, = 0.38) and 0.845 (95%CI 0.383-1.867, = 0.68), respectively. TAPSE with the cutoff 19 mm and visual eyeballing significantly predicted survival with HRs of 0.512 (95%CI 0.296-0.886, = 0.017) and 1.631 (95%CI 1.101-2.416, = 0.015), respectively.

Conclusions: This large-scale all-comer study confirms that RVF is one of the main drivers of mortality in patients with severe isolated TR. However, the current cut-offs for established echocardiographic parameters did not predict survival. Further studies should investigate the prognostic value of higher thresholds for RVF parameters in these patients.
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http://dx.doi.org/10.3390/jcm10112266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197252PMC
May 2021

Renin Feedback Is an Independent Predictor of Outcome in HFpEF.

J Pers Med 2021 May 3;11(5). Epub 2021 May 3.

Division of Cardiology, Medical University of Vienna, 1090 Wien, Austria.

Drugs which interact with the renin angiotensin aldosterone system (RAAS) aim to reduce the negative effects of angiotensin (Ang) II. Treatment with these drugs anticipate a compensatory up-regulation of renin; however, it has been shown that there is a large variability in circulating plasma renin (PRA), even in patients with optimal medical therapy in patients with heart failure (HF) with reduced ejection fraction (HFrEF). Our aim was to measure plasma renin activity (PRA-S), its response to RAAS inhibitor (RAASi) therapies and its effects on outcome in patients with HF with preserved ejection fraction (HFpEF). For this purpose, 150 HFpEF patients were included into a prospective single-center registry. Equilibrium (eq) angiotensin metabolites were measured from serum samples using mass spectroscopy. PRA-S (eqAng I + eqAng II) was calculated and compared in respect to the primary endpoint defined as all-cause death. PRA-S in patients with RAASi therapy was not significantly higher than in patients without RAASi ( = 0.262). Even after adjusting for confounding factors, PRA-S remained predictive for all-cause death in the multivariable model with a hazard ratio of 2.14 (95%CI 1.20-3.82, = 0.010). We conclude that high PRA-S is associated with poor prognosis in patients with HFpEF, regardless of RAASi treatment, which could ultimately result in hyperactivated RAAS and consecutive negative effects on the cardiovascular and renal system, leading to poor outcome in patients with HFpEF.
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http://dx.doi.org/10.3390/jpm11050370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147649PMC
May 2021

Pharmacological inhibition of fatty acid oxidation reduces atherosclerosis progression by suppression of macrophage NLRP3 inflammasome activation.

Biochem Pharmacol 2021 Aug 28;190:114634. Epub 2021 May 28.

Department of Internal Medicine II/Cardiology, Medical University of Vienna, Vienna, Austria.

Background: Inflammation is a key process during atherosclerotic lesion development and propagation. Recent evidence showed clearly that especially the inhibition of interleukin (IL)-1β reduced atherosclerotic adverse events in human patients. Fatty acid oxidation (FAO) was previously demonstrated to interact with the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) pathway which is required for mature IL-1β secretion. To understand possible anti-inflammatory properties of FAO inhibition, we tested the effect of pharmacological FAO inhibition using the inhibitor for long-chain 3-ketoacyl coenzyme A thiolase trimetazidine on atherosclerotic plaque development and inflammation.

Experimental Approach: The effect of FAO inhibition was determined in LDL-R male mice on a C57/BL6 background. In vitro effects of trimetazidine treatment were analyzed in human umbilical vein endothelial cells and human monocyte derived macrophages.

Key Results: We were able to demonstrate that inhibition of FAO reduced atherosclerotic plaque growth. We did not find direct anti-inflammatory properties of trimetazidine in endothelial cells or macrophages in vitro. However, we found that the activation of the NLRP3 system and the secretion of IL-1β were significantly reduced in macrophages after FAO inhibition. These results were confirmed in atherosclerotic lesions of mice treated with trimetazidine as they showed a significant reduction of IL-1β and cleaved caspase-1 in the atherosclerotic lesion as well as of IL-1β and IL-18 in the circulation.

Conclusion: Overall, we therefore suggest that the main mechanism of reducing inflammation of trimetazidine and FAO inhibition is the reduction of the NLRP-3 activation leading to reduced levels of the proinflammatory cytokine IL-1β.
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http://dx.doi.org/10.1016/j.bcp.2021.114634DOI Listing
August 2021

ST-Segment Elevation Myocardial Infarction Following Transcatheter Aortic Valve Replacement.

J Am Coll Cardiol 2021 May;77(17):2187-2199

Hospital Universitario Ramón y Cajal, Madrid, Spain.

Background: Among patients with acute coronary syndrome following transcatheter aortic valve replacement (TAVR), those presenting with ST-segment elevation myocardial infarction (STEMI) are at highest risk.

Objectives: The goal of this study was to determine the clinical characteristics, management, and outcomes of STEMI after TAVR.

Methods: This was a multicenter study including 118 patients presenting with STEMI at a median of 255 days (interquartile range: 9 to 680 days) after TAVR. Procedural features of STEMI after TAVR managed with primary percutaneous coronary intervention (PCI) were compared with all-comer STEMI: 439 non-TAVR patients who had primary PCI within the 2 weeks before and after each post-TAVR STEMI case in 5 participating centers from different countries.

Results: Median door-to-balloon time was higher in TAVR patients (40 min [interquartile range: 25 to 57 min] vs. 30 min [interquartile range: 25 to 35 min]; p = 0.003). Procedural time, fluoroscopy time, dose-area product, and contrast volume were also higher in TAVR patients (p < 0.01 for all). PCI failure occurred more frequently in patients with previous TAVR (16.5% vs. 3.9%; p < 0.001), including 5 patients in whom the culprit lesion was not revascularized owing to coronary ostia cannulation failure. In-hospital and late (median of 7 months [interquartile range: 1 to 21 months]) mortality rates were 25.4% and 42.4%, respectively (20.6% and 38.2% in primary PCI patients), and estimated glomerular filtration rate <60 ml/min (hazard ratio [HR]: 3.02; 95% confidence interval [CI]: 1.42 to 6.43; p = 0.004), Killip class ≥2 (HR: 2.74; 95% CI: 1.37 to 5.49; p = 0.004), and PCI failure (HR: 3.23; 95% CI: 1.42 to 7.31; p = 0.005) determined an increased risk.

Conclusions: STEMI after TAVR was associated with very high in-hospital and mid-term mortality. Longer door-to-balloon times and a higher PCI failure rate were observed in TAVR patients, partially due to coronary access issues specific to the TAVR population, and this was associated with poorer outcomes.
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http://dx.doi.org/10.1016/j.jacc.2021.03.014DOI Listing
May 2021

Impact of anemia on short-term outcomes after TAVR: A subgroup analysis from the BRAVO-3 randomized trial.

Catheter Cardiovasc Interv 2021 Apr 28. Epub 2021 Apr 28.

The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Objectives: To determine the prognostic impact of anemia in patients randomized to bivalirudin or unfractionated heparin (UFH) during transcatheter aortic valve replacement (TAVR).

Background: Whether the periprocedural use of bivalirudin as compared with UFH in anemic patients undergoing TAVR has an impact on outcomes remains unknown.

Methods: The BRAVO-3 trial compared the use of bivalirudin versus UFH in 802 high risk patients undergoing transfemoral TAVR for severe symptomatic aortic stenosis. Patients were stratified according to the presence (defined as hemoglobin levels <13 g/dl in men and <12 g/dl in women) or absence of anemia. The primary outcomes were net adverse cardiac events (NACE; a composite of all-cause mortality, myocardial infarction, stroke, or bleeding) and major bleeding (Bleeding Academic Research Consortium ≥3b) at 30 days.

Results: Among 798 patients with available baseline hemoglobin levels, 427 (54%) were anemic of whom 221 (52%) received bivalirudin. There were no significant differences in NACE and major bleeding at 30 days between patients with and without anemia, irrespective of the type of anticoagulant used (p  = 0.71 for NACE, p  = 1.0 for major bleeding). However, anemic patients had a higher risk of major vascular complications (adjusted OR 2.43, 95% CI 1.42-4.16, p = 0.001), and acute kidney injury (adjusted OR 1.74, 95% CI 1.16-2.59, p = 0.007) compared to non-anemic patients at 30 days.

Conclusions: Anemia was not associated with a higher risk of NACE or major bleeding at 30 days after TAVR without modification of the treatment effects of periprocedural anticoagulation with bivalirudin versus UFH.
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http://dx.doi.org/10.1002/ccd.29753DOI Listing
April 2021

Incidence, predictors, and outcomes associated with acute kidney injury in patients undergoing transcatheter aortic valve replacement: from the BRAVO-3 randomized trial.

Clin Res Cardiol 2021 May 11;110(5):649-657. Epub 2021 Apr 11.

The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, USA.

Background: Acute kidney injury (AKI) is not uncommon in patients undergoing transcatheter aortic valve replacement (TAVR).

Objective: We examined the incidence, predictors, and outcomes of AKI from the BRAVO 3 randomized trial.

Methods: The BRAVO-3 trial included 802 patients undergoing transfemoral TAVR randomized to bivalirudin vs. unfractionated heparin (UFH). The primary endpoint of the trial was Bleeding Academic Research Consortium (BARC) type ≥ 3b bleeding at 48 h. Total follow-up was to 30 days. AKI was adjudicated using the modified RIFLE (Valve Academic Research Consortium, VARC 1) criteria through 30-day follow-up, and in a sensitivity analysis AKI was assessed at 7 days (modified VARC-2 criteria). We examined the incidence, predictors, and 30-day outcomes associated with diagnosis of AKI. We also examined the effect of procedural anticoagulant (bivalirudin or unfractionated heparin, UFH) on AKI within 48 h after TAVR.

Results: The trial population had a mean age of 82.3 ± 6.5 years including 48.8% women with mean EuroScore I 17.05 ± 10.3%. AKI occurred in 17.0% during 30-day follow-up and was associated with greater adjusted risk of 30-day death (13.0% vs. 3.5%, OR 5.84, 95% CI 2.62-12.99) and a trend for more BARC ≥ 3b bleeding (15.1% vs. 8.6%, OR 1.80, 95% CI 0.99-3.25). Predictors of 30-day AKI were baseline hemoglobin, body weight, and pre-existing coronary disease. AKI occurred in 10.7% at 7 days and was associated with significantly greater risk of 30-day death (OR 6.99, 95% CI 2.85-17.15). Independent predictors of AKI within 7 days included pre-existing coronary or cerebrovascular disease, chronic kidney disease (CKD), and transfusion which increased risk, whereas post-dilation was protective. The incidence of 48-h AKI was higher with bivalirudin compared to UFH in the intention to treat cohort (10.9% vs. 6.5%, p = 0.03), but not in the per-protocol assessment (10.7% vs. 7.1%, p = 0.08).

Conclusion: In the BRAVO 3 trial, AKI occurred in 17% at 30 days and in 10.7% at 7 days. AKI was associated with a significantly greater adjusted risk for 30-day death. Multivariate predictors of AKI at 30 days included baseline hemoglobin, body weight, and prior coronary artery disease, and predictors at 7 days included pre-existing vascular disease, CKD, transfusion, and valve post-dilation. Bivalirudin was associated with greater AKI within 48 h in the intention to treat but not in the per-protocol analysis.
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http://dx.doi.org/10.1007/s00392-020-01787-7DOI Listing
May 2021

Myocardial Angiotensin Metabolism in End-Stage Heart Failure.

J Am Coll Cardiol 2021 Apr;77(14):1731-1743

Clinical Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.

Background: The myocardium exhibits an adaptive tissue-specific renin-angiotensin system (RAS), and local dysbalance may circumvent the desired effects of pharmacologic RAS inhibition, a mainstay of heart failure with reduced ejection fraction (HFrEF) therapy.

Objectives: This study sought to investigate human myocardial tissue RAS regulation of the failing heart in the light of current therapy.

Methods: Fifty-two end-stage HFrEF patients undergoing heart transplantation (no RAS inhibitor: n = 9; angiotensin-converting enzyme [ACE] inhibitor: n = 28; angiotensin receptor blocker [ARB]: n = 8; angiotensin receptor neprilysin-inhibitor [ARNi]: n = 7) were enrolled. Myocardial angiotensin metabolites and enzymatic activities involved in the metabolism of the key angiotensin peptides angiotensin 1-8 (AngII) and Ang1-7 were determined in left ventricular samples by mass spectrometry. Circulating angiotensin concentrations were assessed for a subgroup of patients.

Results: AngII and Ang2-8 (AngIII) were the dominant peptides in the failing heart, while other metabolites, especially Ang1-7, were below the detection limit. Patients receiving an ARB component (i.e., ARB or ARNi) had significantly higher levels of cardiac AngII and AngIII (AngII: 242 [interquartile range (IQR): 145.7 to 409.9] fmol/g vs 63.0 [IQR: 19.9 to 124.1] fmol/g; p < 0.001; and AngIII: 87.4 [IQR: 46.5 to 165.3] fmol/g vs 23.0 [IQR: <5.0 to 59.3] fmol/g; p = 0.002). Myocardial AngII concentrations were strongly related to circulating AngII levels. Myocardial RAS enzyme regulation was independent from the class of RAS inhibitor used, particularly, a comparable myocardial neprilysin activity was observed for patients with or without ARNi. Tissue chymase, but not ACE, is the main enzyme for cardiac AngII generation, whereas AngII is metabolized to Ang1-7 by prolyl carboxypeptidase but not to ACE2. There was no trace of cardiac ACE2 activity.

Conclusions: The failing heart contains considerable levels of classical RAS metabolites, whereas AngIII might be an unrecognized mediator of detrimental effects on cardiovascular structure. The results underline the importance of pharmacologic interventions reducing circulating AngII actions, yet offer room for cardiac tissue-specific RAS drugs aiming to limit myocardial AngII/AngIII peptide accumulation and actions.
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http://dx.doi.org/10.1016/j.jacc.2021.01.052DOI Listing
April 2021

Transcatheter treatment by valve-in-valve and valve-in-ring implantation for prosthetic tricuspid valve dysfunction.

Wien Klin Wochenschr 2021 Mar 31. Epub 2021 Mar 31.

Department of Cardiology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Valve degeneration after surgical tricuspid valve replacement or repair is frequent and may require repeat replacement/repair. For high-risk patients, transcatheter valve-in-valve and valve-in-ring procedures have emerged as valuable treatment alternatives. Preprocedural transthoracic echocardiography is the method of choice to detect malfunction of the prosthesis including degenerative stenosis and/or regurgitation requiring reintervention. Subsequently, computed tomography is helpful for detailed anatomical analysis and periprocedural planning. Device selection and sizing depend on the size and structural details of the implanted ring or prosthesis. The procedure is mainly guided by fluoroscopy; however, transesophageal echocardiography provides complementary guidance during device implantation. Preferred access route is the right femoral vein but in cases of more horizontal implants a jugular approach might be feasible. Suitable transcatheter valves are the Edwards Sapien 3 and the Medtronic Melody valves. Differences in surgical prostheses or annuloplasty implants are important for device selection, height consideration and additional ballooning prior to or after implantation. Transesophageal echocardiography postimplantation is convenient for the assessment of transvalvular gradients or paravalvular leaks.
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http://dx.doi.org/10.1007/s00508-021-01842-xDOI Listing
March 2021

Circulating levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) are associated with monocyte subsets in patients with stable coronary artery disease.

J Clin Lipidol 2021 May-Jun;15(3):512-521. Epub 2021 Mar 16.

Department of Internal Medicine II - Division of Cardiology, Medical University of Vienna, Vienna, Austria. Electronic address:

Background: Proprotein convertase subtilisin/kexin type-9 (PCSK9) is an enzyme promoting the degradation of low-density lipoprotein receptors (LDL-R) in hepatocytes. Inhibition of PCSK9 has emerged as a novel target for lipid-lowering therapy. Monocytes are crucially involved in the pathogenesis of atherosclerosis and can be divided into three subsets.

Objective: The aim of this study was to examine whether circulating levels of PCSK9 are associated with monocyte subsets.

Methods: We included 69 patients with stable coronary artery disease. PCSK9 levels were measured and monocyte subsets were assessed by flow cytometry and divided into classical monocytes (CD14++CD16-; CM), intermediate monocytes (CD14++CD16+; IM) and non-classical monocytes (CD14+CD16++; NCM).

Results: Mean age was 64 years and 80% of patients were male. Patients on statin treatment (n = 55) showed higher PCSK9-levels (245.4 (206.0-305.5) ng/mL) as opposed to those without statin treatment (186.1 (162.3-275.4) ng/mL; p = 0.05). In patients on statin treatment, CM correlated with circulating PCSK9 levels (R = 0.29; p = 0.04), while NCM showed an inverse correlation with PCSK9 levels (R = -0.33; p = 0.02). Patients with PCSK9 levels above the median showed a significantly higher proportion of CM as compared to patients with PCSK9 below the median (83.5 IQR 79.2-86.7 vs. 80.4, IQR 76.5-85.2%; p = 0.05). Conversely, PCSK9 levels >median were associated with a significantly lower proportion of NCM as compared to those with PCSK9
Conclusions: We hereby provide a novel link between PCSK9 regulation, innate immunity and atherosclerotic disease in statin-treated patients.
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http://dx.doi.org/10.1016/j.jacl.2021.02.005DOI Listing
March 2021

Comparison of high-sensitivity C-reactive protein vs. C-reactive protein for diagnostic accuracy and prediction of mortality in patients with acute myocardial infarction.

Ann Clin Biochem 2021 07 28;58(4):342-349. Epub 2021 Mar 28.

Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria.

Background: The role of chronic inflammation in the pathogenesis of atherosclerosis has been unequivocally proven. However, the prognostic impact of C-reactive protein, a marker of inflammatory response in patients with acute myocardial infarction has not been fully clarified. Furthermore, there is no direct comparison of the diagnostic accuracy of C-reactive protein and high sensitivity C-reactive protein in the acute myocardial infarction population.

Methods: In this prospective observational cohort study, 344 patients with acute myocardial infarction were enrolled. All-cause mortality was a primary endpoint. Patients were followed prospectively for a median of six years.

Results: The correlation between high sensitivity C-reactive protein and C-reactive protein ( = 0.99;  < 0.001) and the diagnostic accuracy (98.6%) was high. The ROC analysis revealed that C-reactive protein and high sensitivity C-reactive protein had a low AUC for prediction of mortality (C-reactive protein: 0.565, 95% CI [0.462-0.669], vs. high sensitivity C-reactive protein: 0.572, 95% CI [0.470-0.675]) or major adverse cardiac events (C-reactive protein: AUC 0.607, 95% CI [0.405-0.660], vs. high sensitivity C-reactive protein: AUC 0.526, 95% CI [0.398-0.653]) when assessed at time point of acute myocardial infarction. In contrast, longitudinal inflammatory risk assessment with serial C-reactive protein measurements in the stable phase of the disease revealed a 100% specificity, 100% negative predictive value, 32% sensitivity and 12% positive predictive value of C-reactive protein to predict long-term mortality. The Kaplan Meier analysis showed a significant survival benefit for patients at low residual inflammatory risk (=0.014).

Conclusion: C-reactive protein and high sensitivity C-reactive protein provide a similar diagnostic accuracy, highlighting that C-reactive protein might replace high sensitivity C-reactive protein in routine assessments. Furthermore, low inflammatory status during the stable phase after acute myocardial infarction predicts favourable six-year survival.
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http://dx.doi.org/10.1177/00045632211004651DOI Listing
July 2021

Left atrial phasic transport function closely correlates with fibrotic and arrhythmogenic atrial tissue degeneration in atrial fibrillation patients: cardiac magnetic resonance feature tracking and voltage mapping.

Europace 2021 Mar 9. Epub 2021 Mar 9.

Department of Cardiac Electrophysiology, Heart Centre Dresden, Fetscherstraße 76, 01307 Dresden, Germany.

Aims: To characterize the association of phasic left atrial (LA) transport function and LA fibrosis guided by multimodality imaging containing cardiac magnetic resonance imaging (CMR) feature tracking and bipolar voltage mapping.

Methods And Results: Consecutive patients presenting for first-time ablation of atrial fibrillation (AF) were prospectively enrolled. Each patient underwent CMR prior to the ablation procedure. LA phasic indexed volumes (LA-Vi) and emptying fractions (LA-EF) were calculated and CMR feature tracking guided LA wall motion analysis was performed. LA bipolar voltage mapping was carried out in sinus rhythm to find areas of low voltage as a surrogate for fibrosis and arrhythmogenesis. One hundred and sixty-eight patients were enrolled. Low-voltage areas (LVAs) were present in 70 patients (42%). Contrary to LA volume, CMR based LA-EF [odds ratio (OR) 0.88, 95% confidence interval (CI) 0.80-0.96, P = 0.005] and LA booster pump strain rate (SR) (OR 0.98, 95% CI 0.97-0.99, P = 0.001) significantly predicted presence and extent of LVA in multivariate logistic regression analysis for patients scanned in SR. In receiver operating characteristic analysis, LA-EF <40% carried a sensitivity of 83% and specificity of 76% (area under the curve 0.8; 95% CI 0.71-0.89) to predict presence of LVA. For patients scanned in AF only minimal LA-Vi on CMR (OR: 1.06; 95% CI: 1.02-1.10; P = 0.002) predicted presence of LVA.

Conclusion: For patients scanned in SR LA-EF and LA booster pump SR are closely linked to the presence and extent of LA LVA.
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http://dx.doi.org/10.1093/europace/euab052DOI Listing
March 2021

Genome-wide association analysis in dilated cardiomyopathy reveals two new players in systolic heart failure on chromosomes 3p25.1 and 22q11.23.

Eur Heart J 2021 05;42(20):2000-2011

Université de Paris, INSERM, UMR-S970, Integrative Epidemiology of cardiovascular disease, Paris, France.

Aims: Our objective was to better understand the genetic bases of dilated cardiomyopathy (DCM), a leading cause of systolic heart failure.

Methods And Results: We conducted the largest genome-wide association study performed so far in DCM, with 2719 cases and 4440 controls in the discovery population. We identified and replicated two new DCM-associated loci on chromosome 3p25.1 [lead single-nucleotide polymorphism (SNP) rs62232870, P = 8.7 × 10-11 and 7.7 × 10-4 in the discovery and replication steps, respectively] and chromosome 22q11.23 (lead SNP rs7284877, P = 3.3 × 10-8 and 1.4 × 10-3 in the discovery and replication steps, respectively), while confirming two previously identified DCM loci on chromosomes 10 and 1, BAG3 and HSPB7. A genetic risk score constructed from the number of risk alleles at these four DCM loci revealed a 3-fold increased risk of DCM for individuals with 8 risk alleles compared to individuals with 5 risk alleles (median of the referral population). In silico annotation and functional 4C-sequencing analyses on iPSC-derived cardiomyocytes identify SLC6A6 as the most likely DCM gene at the 3p25.1 locus. This gene encodes a taurine transporter whose involvement in myocardial dysfunction and DCM is supported by numerous observations in humans and animals. At the 22q11.23 locus, in silico and data mining annotations, and to a lesser extent functional analysis, strongly suggest SMARCB1 as the candidate culprit gene.

Conclusion: This study provides a better understanding of the genetic architecture of DCM and sheds light on novel biological pathways underlying heart failure.
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http://dx.doi.org/10.1093/eurheartj/ehab030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139853PMC
May 2021

Prescription Patterns of Sodium-Glucose Cotransporter 2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists in Patients with Coronary Artery Disease.

Cardiovasc Drugs Ther 2021 Mar 5. Epub 2021 Mar 5.

Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Purpose: To assess real-world data on the clinical implementation of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) in cardiovascular patients and to investigate barriers to prescribe these agents.

Methods: Patients presenting with coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) between 01/2014 and 04/2020 were included in the present analysis and followed prospectively. All first-time prescriptions of SGLT2i and GLP-1RA were identified.

Results: Among 1498 patients with CAD and T2DM, 17.6% of patients received an SGLT2i and 5.5% a GLP-1RA. The prescription of SGLT2i (+38.7%; p < 0.001) and GLP-1RA (+8%; p = 0.007) significantly increased during the observation period. Considering remuneration criteria for SGLT2i therapy, lowering the GFR cut-off to 30 ml/min/1.73 m would allow additional 26.6% of patients to qualify for an SGLT2i therapy. While SGLT2i therapy was inversely associated with CV mortality (adjusted hazard ratio of 0.18 [95% CI: 0.05-0.76]; p = 0.019), GLP-1RA therapy showed a trend for risk reduction.

Conclusion: The present analysis revealed an infrequent prescription of SGLT2i and GLP-1RAs in patients with T2DM and CAD in clinical practice. Remuneration regulations that better reflect the inclusion criteria of the CV outcome trials would allow more patients at high risk to receive these CV protective drugs. Most importantly, while GLP-1RA therapy showed a trend for risk reduction of cardiovascular mortality, the use of SGLT2i had a strong inverse impact on cardiovascular mortality from a long-term perspective.
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http://dx.doi.org/10.1007/s10557-021-07160-8DOI Listing
March 2021

The Prognostic Potential of Atrial Natriuretic Peptide on the Development of Postoperative Atrial Fibrillation after Cardiac Surgery.

Thromb Haemost 2021 Feb 25. Epub 2021 Feb 25.

Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.

Background:  Postoperative atrial fibrillation (POAF) represents a common complication after cardiac surgery associated with major adverse events and poor patient outcome. Tools for risk stratification of this arrhythmia remain scarce. Atrial natriuretic peptide (ANP) represents an easily assessable biomarker picturing atrial function and strain; however, its prognostic potential on the development of POAF has not been investigated so far.

Methods:  Within the present investigation, 314 patients undergoing elective cardiac surgery were prospectively enrolled. Preoperative mid-region proANP (MR-proANP) values were assessed before the surgical intervention. Patients were followed prospectively and continuously screened for the development of arrhythmic events.

Results:  A total of 138 individuals (43.9%) developed POAF. Median concentrations of MR-proANP were significantly higher within the POAF group ( < 0.001). MR-proANP showed a strong association with the development of POAF with a crude odds ratio (OR) of 1.68 per 1 standard deviation (1-SD; 95% confidence interval [CI]: 1.31-2.15;  < 0.001), which remained stable after comprehensive adjustment for confounders with an adjusted OR of 1.74 per 1-SD (95% CI: 1.17-2.58;  = 0.006). The discriminatory power of MR-proANP for the development of POAF was validated by the category-free net reclassification improvement (0.23 [95% CI: 0.0349-0.4193];  = 0.022) and integrated discrimination increment (0.02 [95% CI: 0.0046-0.0397],  = 0.013).

Conclusion:  MR-proANP proved to be a strong and independent predictor of the development of POAF. Considering a personalized diagnostic and prognostic preoperative work-up, a standardized preoperative evaluation of MR-proANP levels might help to identify patients at risk for development of POAF after cardiac surgery.
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http://dx.doi.org/10.1055/a-1400-6096DOI Listing
February 2021

Severe tricuspid regurgitation: prognostic role of right heart remodelling and pulmonary hypertension.

Eur Heart J Cardiovasc Imaging 2021 Feb 22. Epub 2021 Feb 22.

Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.

Aims: Left heart diseases (LHDs) are the main driving forces for the development of functional tricuspid regurgitation (TR). Therefore, in most cases, the true prognostic value of TR remains concealed by concomitant LHD. This study aimed to analyse right heart remodelling in patients with TR without other valve disease and with normal systolic left ventricular function (sysLVF), and to stratify its prognostic value in the presence (dPH, maximal TR velocity signal (TRVmax) ≥ 3.5 m/s in echocardiography) or absence (nsPH, TRVmax < 3.5m/s) of concomitant pulmonary hypertension (PH).

Methods And Results : We performed an observational analysis of all patients diagnosed with TR in the absence of other valve disease and reduced sysLVF at our institution between 1 January 2003 and 31 December 2013. Five-year mortality was chosen as endpoint. The final cohort entailed 29 979 consecutive patients (median age 60 years, interquartile range 46-70), 49.9% were male, mean follow-up was 95±49 months. Severe TR was present in 790 patients (2.6%). In dPH and in nsPH, severe TR was associated with an excess 5-year mortality that was even more pronounced in the dPH group (58.2% vs. 43.6%, P = 0.001). In nsPH, right ventricular dysfunction predicted mortality. In dPH, mortality was independent of presence or absence of right heart dilatation or dysfunction.

Conclusion: Severe TR without concomitant left heart valve disease or LV systolic dysfunction was a rare disease in this large-scale all-comer population and is associated with an unfavourable prognosis. The differentiation of patients with nsPH and dPH is essential as they present with different patterns of right heart remodelling and with different long-time outcomes.
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http://dx.doi.org/10.1093/ehjci/jeab027DOI Listing
February 2021

Fluid overload in patients undergoing TAVR: what we can learn from the nephrologists.

ESC Heart Fail 2021 04 13;8(2):1408-1416. Epub 2021 Feb 13.

Department of Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, A-1090, Austria.

Aims: Fluid overload (FO) puts aortic stenosis (AS) patients at risk for heart failure (HF) and death. However, conventional FO assessment, including rapid weight gain, peripheral oedema, or chest radiography, is inaccurate. Bioelectrical impedance spectroscopy (BIS) allows objective and reproducible FO quantification, particularly if clinically unapparent. It is used in dialysis patients to establish dry weight goals. BIS has not been tested for prognostication in AS. This study aimed to evaluate whether BIS adds prognostic information in stable patients undergoing transcatheter aortic valve replacement (TAVR).

Methods And Results: Consecutive patients scheduled for TAVR underwent BIS in addition to echocardiographic, clinical, and laboratory assessment. On BIS, mild FO was defined as >1.0 L and severe as >3.0 L. Combined HF hospitalization and/or all-cause death was defined as primary endpoint. Three hundred forty-four patients (81.5 ± 7.2 years old, 47.4% female) were prospectively included. FO by BIS was associated with clinical congestion signs, higher serum markers of cardiac injury, poorer left ventricular function, higher pulmonary pressures, and more severe tricuspid regurgitation (all P < 0.05). Yet, clinical examination was unremarkable in >30% in mild FO, only detected by BIS. During 12.1 ± 5.5 months, 67 (19.5%) events were recorded (40 deaths, 15 HF hospitalizations, and 12 both). Quantitatively, every 1 L increase in FO was associated with a 24% (HR 1.24, 95% CI 1.13-1.35, P < 0.001) increase in event hazard. This association persisted after adjustment for STS/EuroSCORE-II, NT-proBNP, left ventricular ejection fraction, and renal function.

Conclusions: In patients undergoing TAVR, FO by BIS is strongly associated with adverse outcomes. BIS measurement conveys prognostic information not represented in any currently used AS/TAVR risk assessments.
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http://dx.doi.org/10.1002/ehf2.13226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006739PMC
April 2021

Pacemaker lead-associated tricuspid regurgitation in patients with or without pre-existing right ventricular dilatation.

Clin Res Cardiol 2021 Jun 10;110(6):884-894. Epub 2021 Feb 10.

Department of Cardiology, Medical University of Vienna, Vienna, Austria.

Background: Transcatheter tricuspid valve intervention became an option for pacemaker lead-associated tricuspid regurgitation. This study investigated the progression of tricuspid regurgitation (TR) in patients with or without pre-existing right ventricular dilatation (RVD) undergoing pacemaker implantation.

Methods: Patients were included if they had implantation of transtricuspid pacemaker lead and completed echocardiography before and after implantation. The cohort was divided in patients with and without RVD (cut-off basal RV diameter ≥ 42 mm). TR was graded in none/mild, moderate, and severe. Worsening of one grade was defined as progression. Survival analyses were plotted for 10 years.

Results: In total, 990 patients were analyzed (24.5% with RVD). Progression of TR occurred in 46.1% of patients with RVD and in 25.6% of patients without RVD (P < 0.001). Predictors for TR progression were RV dilatation (OR 2.04; 95% CI 1.27-3.29; P = 0.003), pre-existing TR (OR 4.30; 95% CI 2.51-7.38; P < 0.001), female sex (OR 1.68; 95% CI 1.16-2.43; P = 0.006), single RV lead (OR 1.67; 95% CI 1.09-2.56; P = 0.018), mitral regurgitation (OR 2.08; 95% CI 1.42-3.05; P < 0.001), and enlarged left atrium (OR 1.98; 95% CI 1.07-3.67; P = 0.03). Survival-predictors were pacemaker lead-associated TR (HR 1.38; 95% CI 1.04-1.84; P = 0.028), mitral regurgitation (HR 1.34; 95% CI 1.02-1.77; P = 0.034), heart failure (HR 1.75; 95% CI 1.31-2.33; P < 0.001), kidney disease (HR 1.62; 95% CI 1.25-2.11; P < 0.001), and age ≥ 80 years (HR 2.84; 95% CI 2.17-3.71; P < 0.001).

Conclusions: Patients with RVD receiving pacemaker suffered from increased TR progression, leading to decreased survival.
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http://dx.doi.org/10.1007/s00392-021-01812-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166708PMC
June 2021

Effects of Nicorandil on Inflammation, Apoptosis and Atherosclerotic Plaque Progression.

Biomedicines 2021 Jan 27;9(2). Epub 2021 Jan 27.

Department of Internal Medicine II-Division of Cardiology, Medical University of Vienna, 1090 Vienna, Austria.

Nicorandil, a balanced vasodilator, is used in the second-line therapy of angina pectoris. In this study, we aimed to illuminate the effects of nicorandil on inflammation, apoptosis, and atherosclerotic plaque progression. Twenty-five LDL-R -/- mice were fed a high-fat diet for 14 weeks. After 6 weeks mice were randomly allocated to treatment with nicorandil (10 mg/kg/day) or tap water. Nicorandil treatment led to a more stable plaque phenotype, displaying an increased thickness of the fibrous cap ( = 0.014), a significant reduction in cholesterol clefts ( = 0.045), and enhanced smooth muscle cell content ( = 0.009). In endothelial cells nicorandil did not reduce the induction of adhesion molecules or proinflammatory cytokines. In HO challenged endothelial cells, pretreatment with nicorandil significantly reduced the percentage of late apoptotic/necrotic cells ( = 0.016) and the ratio of apoptotic to living cells ( = 0.036). Atherosclerotic lesions of animals treated with nicorandil exhibited a significantly decreased content of cleaved caspase-3 ( = 0.034), lower numbers of apoptotic nuclei ( = 0.040), and reduced 8-oxogunanine staining ( = 0.039), demonstrating a stabilizing effect of nicorandil in established atherosclerotic lesions. We suggest that nicorandil has a positive effect on atherosclerotic plaque stabilization by reducing apoptosis.
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http://dx.doi.org/10.3390/biomedicines9020120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912627PMC
January 2021

Circulating MicroRNAs and Monocyte-Platelet Aggregate Formation in Acute Coronary Syndrome.

Thromb Haemost 2021 Jul 14;121(7):913-922. Epub 2021 Jan 14.

Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.

Background:  Monocyte-platelet aggregates (MPAs) are a sensitive marker of in vivo platelet activation in acute coronary syndrome (ACS) and associated with clinical outcomes. MicroRNAs (miRs) play an important role in the regulation of platelet activation, and may influence MPA formation. Both, miRs and MPA, could be influenced by the type of P2Y12 inhibitor.

Aim:  To study the association of platelet-related miRs with MPA formation in ACS patients on dual antiplatelet therapy (DAPT), and to compare miRs and MPA levels between prasugrel- and ticagrelor-treated patients.

Methods And Results:  We analyzed 10 circulating platelet-related miRs in 160 consecutive ACS patients on DAPT with low-dose aspirin and either prasugrel ( = 80) or ticagrelor ( = 80). MPA formation was measured by flow cytometry without addition of platelet agonists and after simulation with the toll-like receptor (TLR)-1/2 agonist Pam3CSK4, adenosine diphosphate (ADP), or arachidonic acid (AA). In multivariate regression analyses, we identified miR-21 (β = 9.50, 95% confidence interval [CI]: 1.60-17.40,  = 0.019) and miR-126 (β = 7.50, 95% CI: 0.55-14.44,  = 0.035) as independent predictors of increased MPA formation in vivo and after TLR-1/2 stimulation. In contrast, none of the investigated miRs was independently associated with MPA formation after stimulation with ADP or AA. Platelet-related miR expression and MPA formation did not differ significantly between prasugrel- and ticagrelor-treated patients.

Conclusion:  Platelet-related miR-21 and miR-126 are associated with MPA formation in ACS patients on DAPT. miRs and MPA levels were similar in prasugrel- and ticagrelor-treated patients.
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http://dx.doi.org/10.1055/s-0040-1722226DOI Listing
July 2021

Association of Soluble Suppression of Tumorigenesis 2 (sST2) With Platelet Activation, Monocyte Tissue Factor and Ischemic Outcomes Following Angioplasty and Stenting.

Front Cardiovasc Med 2020 22;7:605669. Epub 2020 Dec 22.

Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.

Peripheral artery disease (PAD) patients undergoing infrainguinal angioplasty with stenting suffer high rates of target lesion restenosis and ischemic events. Blood-based prognostic markers in these patients are currently limited. The IL-33/ST2-system is involved in atherothrombosis. Soluble ST2 has been proposed as a biomarker in patients with cardiovascular disease. To investigate the association of sST2 with platelet activation and monocyte tissue factor (TF) in 316 patients undergoing elective angioplasty and stenting for cardiovascular disease, and its predictive value for ischemic outcomes following infrainguinal angioplasty with stent implantation in 104 PAD patients within this cohort. Circulating levels of sST2, platelet surface P-selectin, monocyte TF expression as well as soluble P-selectin were determined in 316 consecutive patients on dual antiplatelet therapy following angioplasty and stenting. sST2 was independently associated with soluble P-selectin (B = 6.4, 95% CI 2.0-10.7, = 0.004) and TF expression (B = 0.56, 95% CI 0.02-1.1, = 0.041) but not with platelet surface P-selectin (B = 0.1, 95% CI -0.1-0.3, = 0.307) after adjustment for age, sex, clinical risk factors and inflammatory parameters. During the follow-up of 24 months, the primary endpoint occurred in 41 of 104 PAD patients (39.4%). However, circulating levels of sST2 did not predict the primary endpoint in PAD patients (HR 1.1, 95% CI 0.76-1.71, = 0.527). sST2 is associated with soluble P-selectin and monocyte TF expression in atherosclerosis but not with ischemic outcomes following infrainguinal angioplasty with stent implantation for PAD.
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http://dx.doi.org/10.3389/fcvm.2020.605669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782352PMC
December 2020

Transcatheter TricValve implantation for the treatment of severe tricuspid regurgitation.

Eur Heart J Cardiovasc Imaging 2021 Jun;22(7):e92

Department of Cardiology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.

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http://dx.doi.org/10.1093/ehjci/jeaa348DOI Listing
June 2021

Right ventricular function and outcome in patients undergoing transcatheter aortic valve replacement.

Eur Heart J Cardiovasc Imaging 2020 Dec 30. Epub 2020 Dec 30.

Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.

Aims: Right ventricular dysfunction (RVD) on echocardiography has been shown to predict outcomes in patients undergoing transcatheter aortic valve replacement (TAVR). However, a comparison with the gold standard, RV ejection fraction (EF) on cardiovascular magnetic resonance (CMR), has never been performed.

Methods And Results: Consecutive patients scheduled for TAVR underwent echocardiography and CMR. RV fractional area change (FAC), tricuspid annular plane systolic excursion, RV free-lateral-wall tissue Doppler (S'), and strain were assessed on echocardiography, and RVEF on CMR. Patients were prospectively followed. Adjusted regression analyses were used to report the strength of association per 1-SD decline for each RV function parameter with (i) N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels, (ii) prolonged in-hospital stay (>14 days), and (iii) a composite of heart failure hospitalization and death. Two hundred and four patients (80.9 ± 6.6 y/o; 51% female; EuroSCORE-II: 6.3 ± 5.1%) were included. At a cross-sectional level, all RV function parameters were associated with NT-proBNP levels, but only FAC and RVEF were significantly associated with a prolonged in-hospital stay [adjusted odds ratio 1.86, 95% confidence interval (CI) 1.07-3.21; P = 0.027 and 2.29, 95% CI 1.43-3.67; P = 0.001, respectively]. A total of 56 events occurred during follow-up (mean 13.7 ± 9.5 months). After adjustment for the EuroSCORE-II, only RVEF was significantly associated with the composite endpoint (adjusted hazard ratio 1.70, 95% CI 1.32-2.20; P < 0.001).

Conclusion: RVD as defined by echocardiography is associated with an advanced disease state but fails to predict outcomes after adjustment for pre-existing clinical risk factors in TAVR patients. In contrast, RVEF on CMR is independently associated with heart failure hospitalization and death.
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http://dx.doi.org/10.1093/ehjci/jeaa342DOI Listing
December 2020

Sex Differences in Left Ventricular Remodeling and Outcomes in Chronic Aortic Regurgitation.

J Clin Med 2020 Dec 18;9(12). Epub 2020 Dec 18.

Division of Cardiology, Medical University of Vienna, 1090 Vienna, Austria.

Background: Left ventricular (LV) dilatation is a key compensatory feature in patients with chronic aortic regurgitation (AR). However, sex-differences in LV remodeling and outcomes in chronic AR have been poorly investigated so far.

Methods: We performed cardiovascular magnetic resonance imaging (CMR) including phase-contrast velocity-encoded imaging for the measurement of regurgitant fraction (RegF) at the sinotubular junction, in consecutive patients with at least mild AR on echocardiography. We assessed LV size (end-diastolic volume indexed to body surface area, LVEDV/BSA) and investigated sex differences between LV remodeling and increasing degrees of AR severity. Cox-regression models were used to test differences in outcomes between men and women using a composite of heart failure hospitalization, unscheduled AR intervention, and cardiovascular death.

Results: 270 consecutive patients (59.6% male, 59.8 ± 20.8 y/o, 59.6% with at least moderate AR on echocardiography) were included. On CMR, mean RegF was 18.1 ± 17.9% and a total of 65 (24.1%) had a RegF ≥ 30%. LVEDV/BSA was markedly closer related with AR severity (RegF) in men compared to women. Each 1-SD increase in LVEDV/BSA (mL/m) was associated with a 9.7% increase in RegF in men and 5.9% in women, respectively (-value for sex-interaction < 0.001). Based on previously published reference values, women-in contrast to men-frequently had a normal LV size despite severe AR (e.g., for LVEDV/BSA on CMR: 35.3% versus 8.7%, < 0.001). In a Cox-regression model adjusted for age, LVEDV/BSA and RegF, women were at significantly higher risk for the composite endpoint when compared to men (adj. HR 1.81 (95%CI 1.09-3.03), = 0.022).

Conclusion: In patients with chronic AR, LV remodeling is a hallmark feature in men but not in women. Severity of AR may be underdiagnosed in female patients in the absence of LV dilatation. Future studies need to address the dismal prognosis in female patients with chronic AR.
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http://dx.doi.org/10.3390/jcm9124100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767247PMC
December 2020

The Age-Specific Impact of Cellular Immunity on Long-Term Outcome after Acute Coronary Syndrome.

Thromb Haemost 2020 Dec 18. Epub 2020 Dec 18.

Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Austria.

Background:  Personalized risk stratification after acute coronary syndrome (ACS) remains a challenging field in the aging society. Easily applicable strategies for risk prediction of adverse events from an age-specific perspective are needed. Considering the association of cellular immunity with coronary vessel disease, these cell lines mirror a reasonable value for risk assessment. Therefore, we aimed to elucidate the prognostic value of cellular immunity on long-term outcome after ACS from an age-specific perspective.

Methods:  Patients presenting with ACS at the Vienna General Hospital admitted between December 1996 and January 2010 were enrolled within a clinical registry including standardized assessment of peripheral blood samples and immune phenotyping. Cox-regression hazards analysis was performed to elucidate the impact of cellular immunity on survival.

Results:  A total of 832 patients were included within the final analysis and stratified according to age into individuals <65 years ( = 416) and ≥65 years ( = 416). After a median follow-up time of 8.6 years, a total of 516 (62.0%) individuals died. We found that the fraction of lymphocytes (adjusted hazard ratio [HR] of 0.61 [95% confidence interval, CI: 0.45-0.82];  = 0.001), the fraction of neutrophil granulocytes (adjusted HR of 5.01 [95% CI: 1.62-15.46];  = 0.005), and the neutrophil-to-lymphocyte ratio (NLR; adjusted HR of 1.47 [95% CI: 1.16-1.87];  = 0.002) showed a strong and independent association with mortality in individuals ≥65 years. Notably, there was no effect on outcome observed for any of the tested cell lines in patients <65 years.

Conclusion:  The present investigation highlighted a strong and independent age-specific effect of both the fraction of neutrophil granulocytes and lymphocytes as well as the NLR on outcome. Considering an age-dependent risk stratification, these routinely available values can be easily used to identify patients at risk for fatal events and contribute to proper secondary prevention after ACS.
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http://dx.doi.org/10.1055/a-1340-2055DOI Listing
December 2020

Editorial: Antithrombotic Treatment in Transcatheter Structural Cardiac Interventions and After Cardiac Device Implantation.

Front Cardiovasc Med 2020 12;7:616638. Epub 2020 Nov 12.

Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.

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http://dx.doi.org/10.3389/fcvm.2020.616638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689152PMC
November 2020

The COVID-19 burden for health care professionals: Results of a global survey.

Eur J Intern Med 2021 01 12;83:96-98. Epub 2020 Nov 12.

Department of Internal Medicine II, Medical University of Vienna, Austria.

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http://dx.doi.org/10.1016/j.ejim.2020.11.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659805PMC
January 2021

An Integrated Imaging and Circulating Biomarker Approach for Secondary Tricuspid Regurgitation.

J Pers Med 2020 Nov 16;10(4). Epub 2020 Nov 16.

Department of Internal Medicine II, Medical University of Vienna, 1090 Wien, Austria.

Secondary tricuspid regurgitation (sTR) is frequent among patients with heart failure with reduced ejection fraction (HFrEF), however it confers considerable diagnostic challenges. The assessment of neurohumoral activation may constitute a valuable supplement to the current imaging-based diagnostic process. This study sought to investigate the expression of complementary biomarkers in sTR and to evaluate the effectiveness of integrating their assessment into the diagnostic process. We enrolled 576 HFrEF patients recording echocardiographic and biochemical measurements, i.e., N-terminal pro-B-type natriuretic peptide, mid-regional pro-atrial natriuretic peptide (MR-proANP), mid-regional pro-adrenomedullin, C-terminal pro-endothelin-1 (CT-pro-ET1), and copeptin. Plasma levels of the aforementioned neurohormones were significantly elevated with increasing sTR severity ( < 0.001 for all). CT-pro-ET1 and MR-proANP were the closest related to severe sTR (adj. OR 1.46; 95%CI 1.11-1.91, = 0.006 and adj. OR 1.45, 95%CI 1.13-1.87, = 0.004, respectively). In patients with moderate-to-severe sTR, adding selected biomarkers (i.e., CT-pro-ET1 and MR-proANP) resulted in a substantial improvement in the discriminatory power regarding long-term mortality (C-statistic: 0.54 vs. 0.65, < 0.001; continuous NRI 57%, < 0.001). Circulating biomarkers closely relate to sTR severity and correlate with hemodynamic and morphologic mechanisms of sTR. Specifically, MR-proANP and CT-pro-ET1 are closely linked to the presence of severe sTR, and a combined assessment with the guideline recommended echocardiographic grading significantly improves individual risk stratification.
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http://dx.doi.org/10.3390/jpm10040233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712812PMC
November 2020

What Type of Patients Did PARAGON-HF Select? Insights from a Real-World Prospective Cohort of Patients with Heart Failure and Preserved Ejection Fraction.

J Clin Med 2020 Nov 15;9(11). Epub 2020 Nov 15.

Division of Cardiology, Klinik Favoriten, Kundratstraße 3, 1100 Vienna, Austria.

The PARAGON-HF clinical trial suggested that sacubitril/valsartan may become a treatment option for particular subgroups of patients with heart failure and preserved ejection fraction (HFpEF). However, the proportion of real-world HFpEF patients who are theoretically superimposable with the PARAGON-HF population is yet unknown. The present study was performed to define the proportion of real-world PARAGON-HF-like patients and to describe their clinical characteristics and long-term prognosis in comparison with those who would not meet PARAGON-HF criteria. We systematically applied PARAGON-HF inclusion and exclusion criteria to a total of 427 HFpEF patients who have been participating in a prospective national registry between December 2010 and December 2019. In total, only 170 (39.8%) registry patients were theoretically eligible for PARAGON-HF. Patients not meeting inclusion criteria (41.0%) were less impaired with respect to exercise capacity (median 6-min walk distance: 385 m (IQR: 300-450) versus 323 m (IQR: 240-383); < 0.001) had lower pulmonary pressures (mean pulmonary artery pressure (mPAP): 31.2 mmHg, standard deviation (SD): ±10.2 versus 32.8 mmHg, SD: ±9.7; < 0.001) and better outcomes (log-rank: < 0.001) as compared to the PARAGON-like cohort. However, patients theoretically excluded from the trial (19.2%) were those with most advanced heart failure symptoms (median 6-min walk test: 252 m (IQR: 165-387); < 0.001), highest pulmonary pressures (mPAP: 38.2 mmHg, SD: ±12.4; < 0.001) and worst outcome (log-rank: = 0.037). We demonstrate here that < 40% of real-world HFpEF patients meet eligibility criteria for PARAGON-HF. We conclude that despite reasons for optimism after PARAGON-HF, a large proportion of HFpEF patients will remain without meaningful treatment options.
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http://dx.doi.org/10.3390/jcm9113669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697501PMC
November 2020