Journal: Clin Res Cardiol

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<div><h4>Long-term risk associated with clonal hematopoiesis in patients with severe aortic valve stenosis undergoing TAVR.</h4><i>Mas-Peiro S, Pergola G, Berkowitsch A, Meggendorfer M, ... Dimmeler S, Zeiher AM</i><br /><b>Background</b><br />Mutations in the clonal hematopoiesis of indeterminate potential (CHIP)-driver genes DNMT3A and TET2 have been previously shown to be associated with short-term prognosis in patients undergoing TAVR for aortic valve stenosis. We aimed to extend and characterize these findings on long-term outcome in a large cohort.<br /><b>Methods</b><br />A total of 453 consecutive patients undergoing TAVR were included in an up to 4-year follow-up study. Next-generation sequencing was used to identify DNMT3A- and/or TET2-CHIP-driver mutations. Primary endpoint was all-cause mortality. Since CHIP-driver mutations appear to be closely related to DNA methylation, results were also assessed in patients who never smoked, a factor known to interfere with DNA methylation.<br /><b>Results</b><br />DNMT3A-/TET2-CHIP-driver mutations were present in 32.4% of patients (DNMT3A n = 92, TET2 n = 71), and were more frequent in women (52.4% vs. 38.9%, p = 0.007) and older participants (83.3 vs. 82.2 years, p = 0.011), while clinical characteristics or blood-derived parameters did not differ. CHIP-driver mutations were associated with a significantly higher mortality up to 4 years after TAVR in both univariate (p = 0.031) and multivariate analyses (HR 1.429, 95%CI 1.014-2.013, p = 0.041). The difference was even more pronounced (p = 0.011) in never smokers. Compared to TET2 mutation carriers, patients with DNMT3A mutations had significantly less frequently concomitant coronary and peripheral artery disease.<br /><b>Conclusion</b><br />DNMT3A- and TET2-CHIP-driver mutations are associated with long-term mortality in patients with aortic valve stenosis even after a successful TAVR. The association is also present in never smokers, in whom no biasing effect from smoking on DNA methylation is to be expected.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 21 Jan 2023; epub ahead of print</small></div>
Mas-Peiro S, Pergola G, Berkowitsch A, Meggendorfer M, ... Dimmeler S, Zeiher AM
Clin Res Cardiol: 21 Jan 2023; epub ahead of print | PMID: 36680616
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<div><h4>Prediction of conduction disturbances in patients undergoing transcatheter aortic valve replacement.</h4><i>Pavlicek V, Mahfoud F, Bubel K, Fries P, ... Scheller B, Ukena C</i><br /><b>Aim</b><br />Transcatheter aortic valve replacement (TAVR) can cause intraventricular conduction disturbances (ICA), particularly left bundle branch block (BBB) and high-degree atrioventricular block (HAVB). The aim of this study was to investigate clinical, anatomical, procedural, and electrophysiological parameters predicting ICA after TAVR.<br /><b>Methods</b><br />Patients with severe aortic stenosis (n = 203) without pacing devices undergoing TAVR with a self-expanding (n = 103) or balloon-expanding (n = 100) valve were enrolled. Clinical and anatomical parameters, such as length of the membranous septum (MS) and implantation depth, were assessed. His-ventricular interval (HVi) before and after implantation was determined. 12-lead-electrocardiograms (ECG) before, during and after 3 and 30 days after TAVR were analyzed for detection of any ICA.<br /><b>Results</b><br />Among 203 consecutive patients (aortic valve area 0.78 ± 0.18 cm<sup>2</sup>, age 80 ± 6 years, 54% male, left ventricular ejection fraction 52 ± 10%), TAVR led to a significant prolongation of infranodal conduction in all patients from 49 ± 10 ms to 59 ± 16 ms (p = 0.01). The HVi prolongation was independent of valve types, occurrence of HAVB or ICA. Fifteen patients (7%) developed HAVB requiring permanent pacemaker (PPM) implantation and 63 patients (31%) developed ICA within 30 days. Pre-existing BBB (OR 11.64; 95% CI 2.87-47.20; p = 0.001), new-onset left BBB (OR 15.72; 95% CI 3.05-81.03; p = 0.001), and diabetes mellitus (OR 3.88; 95% CI 1.30-15.99; p = 0.02) independently predicted HAVB requiring PPM. Neither pre-existing right BBB, a prolonged postHVi, increases in PR duration, any of the TAVR implantation procedural and anatomic nor echocardiographic characteristics were predictive for later HAVB.<br /><b>Conclusions</b><br />New-onset left BBB and diabetes mellitus independently predicted HAVB requiring PPM after TAVR and helped to identify patients at risk. Electrophysiologic study (EPS) of atrioventricular conduction was neither specific nor predictive of HAVB and can be skipped.<br /><b>Trial registration number</b><br />NCT04128384 ( https://www.<br /><b>Clinicaltrials</b><br />gov ).<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 21 Jan 2023; epub ahead of print</small></div>
Pavlicek V, Mahfoud F, Bubel K, Fries P, ... Scheller B, Ukena C
Clin Res Cardiol: 21 Jan 2023; epub ahead of print | PMID: 36680617
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<div><h4>Reduction of permanent pacemaker implantation by using the cusp overlap technique in transcatheter aortic valve replacement: a meta-analysis.</h4><i>Rawish E, Macherey S, Jurczyk D, Pätz T, ... Frerker C, Schmidt T</i><br /><b>Background</b><br />The need for permanent pacemaker (PPM) implantation is a common complication after transcatheter aortic valve replacement (TAVR). Deep implantation position is a risk factor for PPM implantation. Thus, in the field of self-expandable (SE) transcatheter heart valves (THV) cusp overlap projection (COP) technique was implemented to reduce parallax, allowing a more precise guidance of implantation depth.<br /><b>Aims</b><br />This meta-analysis aims to report the outcome of patients undergoing TAVR with SE THV using COP versus conventional implantation technique (CIT).<br /><b>Methods</b><br />Systematical search in MEDLINE and EMBASE yielded five observational controlled studies comparing both implantation techniques for the SE Evolut prosthesis (Medtronic Intern. Ltd., CA, USA) and fulfilling the inclusion criteria for meta-analysis.<br /><b>Results</b><br />Totally, 1227 patients were included, comprising 641 who underwent COP and 586 CIT TAVR. Incidence of post-procedural need for PPM implantation was significantly lower in COP group (9.8% vs 20.6%; OR = 0.43; p < 0.00001). This was accompanied by significantly higher implantation position in COP group (mean difference distance from distal end of the intraventricular portion of the THV to the non-coronary cusp (NCC): - 1.03 mm; p = 0.00001). Incidence of new-onset left bundle branch block did not differ. Regarding procedural and 30-day mortality, technical success, post-procedural aortic regurgitation, and rates of multiple device implantation, no difference between COP and CIT was found.<br /><b>Conclusion</b><br />COP is an effective and safe implantation technique to reduce the need for a permanent pacemaker implantation during TAVR with SE Evolut prosthesis.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 19 Jan 2023; epub ahead of print</small></div>
Rawish E, Macherey S, Jurczyk D, Pätz T, ... Frerker C, Schmidt T
Clin Res Cardiol: 19 Jan 2023; epub ahead of print | PMID: 36656375
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<div><h4>Prognostic impact and diagnostic value of invasively derived hemodynamic measures in patients with severe aortic stenosis undergoing TAVI.</h4><i>Grundmann D, Goßling A, Schmidt L, Voigtlaender L, ... Seiffert M, Schofer N</i><br /><b>Background</b><br />Ejection time (ET), acceleration time (AT) and time between left ventricular and aortic systolic pressure peaks (T-LVAo) might be of diagnostic and prognostic use in patients with aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI).<br /><b>Aim</b><br />We aimed to assess the diagnostic value and prognostic impact of invasively measured ET, AT, and T-LVAo in patients undergoing TAVI.<br /><b>Methods</b><br />A total of 1274 patients received invasive measurement of ET, AT and T-LVAo prior to TAVI. Anatomic AS severity was assessed by CT-derived aortic valve calcification density (AVC<sub>d</sub>). Impact on all-cause mortality was retrospectively analyzed.<br /><b>Results</b><br />In multivariable linear regression, T-LVAo showed the strongest correlation with AVC<sub>d</sub>. No prognostic impact of T-LVAo was found according to uni- and multivariable analyses. In contrast, using an individual C-statistic derived cutoff (C<sub>D</sub>), patients with ET or AT ≥ C<sub>D</sub> showed lower mortality rates compared to patients with ET or AT < C<sub>D</sub> (1-year mortality: ET ≥ vs. < C<sub>D</sub>: 15.01vs. 33.1%, AT ≥ vs < C<sub>D</sub> 16.3 vs. 26.5%, p < 0.001). Moreover, multivariable analysis identified ET ≥ C<sub>D</sub> (HR 0.61 [95% CI 0.43-0.87; p < 0.007]) to be associated with beneficial outcome after TAVI, independent from clinical risk factors and echocardiography-derived parameters.<br /><b>Conclusion</b><br />Among the studied hemodynamic parameters T-LVAo provides the highest diagnostic value, whereas ET is an outcome predictor beyond clinical risk factors and echocardiographic parameters in AS patients following TAVI. These parameters could be of considerable use in diagnostic evaluation and risk assessment of patients scheduled for TAVI. T-LVAo (yellow): defined as time between left ventricular and aortic systolic pressure peaks. ET (green): Ejection Time defined as time from the start to flow end. AT (orange): Acceleration time defined as time from the start to the peak flow. AOP: aortic pressure, AVC: aortic valve calcification, CI: confidence interval, HGAS: high-gradient aortic stenosis, LGAS: low-gradient aortic stenosis, LVP: left ventricular pressure, SD: standard deviation.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 19 Jan 2023; epub ahead of print</small></div>
Grundmann D, Goßling A, Schmidt L, Voigtlaender L, ... Seiffert M, Schofer N
Clin Res Cardiol: 19 Jan 2023; epub ahead of print | PMID: 36656376
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<div><h4>Disconnect between the effects of serelaxin on renal function and outcome in acute heart failure.</h4><i>Beldhuis IE, Ter Maaten JM, Figarska SM, Damman K, ... Metra M, Voors AA</i><br /><b>Background</b><br />We aimed to study whether improvement in renal function by serelaxin in patients who were hospitalized for acute heart failure (HF) might explain any potential effect on clinical outcomes.<br /><b>Methods</b><br />We included 6318 patients from the RELAXin in AHF-2 (RELAX-AHF2) study. Improvement in renal function was defined as a decrease in serum creatinine of ≥ 0.3 mg/dL and ≥ 25%, or increase in estimated glomerular filtration rate of ≥ 25% between baseline and day 2. Worsening renal function (WRF) was defined as the reverse. We performed causal mediation analyses regarding 180-day all-cause mortality (ACM), cardiovascular death (CVD), and hospitalization for HF/renal failure.<br /><b>Results</b><br />Improvement in renal function was more frequently observed with serelaxin when compared with placebo [OR 1.88 (95% CI 1.64-2.15, p < 0.0001)], but was not associated with subsequent clinical outcomes. WRF occurred less frequent with serelaxin [OR 0.70 (95% CI 0.60-0.83, p < 0.0001)] and was associated with increased risk of ACM, worsening HF and the composite of CVD and HF or renal failure hospitalization. Improvement in renal function did not mediate the treatment effect of serelaxin [CVD HR 1.01 (0.99-1.04), ACM HR 1.01 (0.99-1.03), HF/renal failure hospitalization HR 0.99 (0.97-1.00)].<br /><b>Conclusions</b><br />Despite the significant improvement in renal function by serelaxin in patients with acute HF, the potential beneficial treatment effect was not mediated by improvement in renal function. These data suggest that improvement in renal function might not be a suitable surrogate marker for potential treatment efficacy in future studies with novel relaxin agents in acute HF. Central illustration. Conceptual model explaining mediation analysis; treatment efficacy of heart failure therapies mediated by renal function.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 19 Jan 2023; epub ahead of print</small></div>
Beldhuis IE, Ter Maaten JM, Figarska SM, Damman K, ... Metra M, Voors AA
Clin Res Cardiol: 19 Jan 2023; epub ahead of print | PMID: 36656377
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<div><h4>The influence of renal disease on outcomes and cardiac remodeling following surgical mitral valve replacement.</h4><i>El-Andari R, Bozso SJ, Fialka NM, Kang JJH, ... Nagendran J, Nagendran J</i><br /><b>Objectives</b><br />Chronic kidney disease (CKD) is increasingly prevalent in patients undergoing mitral valve replacement (MVR). While CKD is known to result in suboptimal outcomes for patients with mitral valve disease, there is limited literature evaluating the long-term outcomes and cardiac remodeling of patients with CKD undergoing MVR. We present the first analysis coupling long-term outcomes of combined morbidity, mortality, and cardiac remodeling post-MVR in patients with CKD.<br /><b>Methods</b><br />Patients with varying degrees of CKD undergoing MVR from 2004 to 2018 were compared. Patients were grouped by estimated glomerular filtration rate (eGFR) > 90 mL/min/1.73m<sup>2</sup> (n = 109), 60-89 mL/min/1.73m<sup>2</sup> (450), 30-59 mL/min/1.73m<sup>2</sup> (449), < 30 mL/min/1.73m<sup>2</sup> (60). The primary outcome was mortality. Secondary outcomes included measures of postoperative morbidity and cardiac remodeling.<br /><b>Results</b><br />One-year mortality was significantly increased in patients with eGFR < 30 (p = 0.023). Mortality at 7 years was significantly increased in patients with eGFR < 30 mL/min/1.73m<sup>2</sup> (p < 0.001). Multivariable regression analysis of 7-year all-cause mortality indicated an eGFR of 15 mL/min/1.73m<sup>2</sup> (HR 4.03, 95% CI 2.54-6.40) and 30 mL/min/1.73m<sup>2</sup> (HR 2.17 95% CI 1.55-3.05) were predictive of increased mortality. Reduced eGFR predicted the development of postoperative sepsis (p = 0.002), but not other morbidities. Positive cardiac remodeling of the left ventricle, left atrium, and valve gradients were identified postoperatively for patients with eGFR > 30 mL/min/1.73m<sup>2</sup> while patients with eGFR < 30 mL/min/1.73m<sup>2</sup> did not experience the same changes.<br /><b>Conclusions</b><br />CKD is predictive of inferior clinical and echocardiographic outcomes in patients undergoing MVR and consequently requires careful preoperative consideration and planning. Further investigation into optimizing the postoperative outcomes of this patient population is necessary.<br /><br />© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.<br /><br /><small>Clin Res Cardiol: 19 Jan 2023; epub ahead of print</small></div>
El-Andari R, Bozso SJ, Fialka NM, Kang JJH, ... Nagendran J, Nagendran J
Clin Res Cardiol: 19 Jan 2023; epub ahead of print | PMID: 36656378
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<div><h4>Adverse cardiovascular and metabolic perturbations among older women: \'fat-craving\' hearts.</h4><i>Ho JS, Wong JJ, Gao F, Wee HN, ... Kovalik JP, Koh AS</i><br /><b>Background</b><br />Despite known sex-based differences in cardiovascular aging, differences in aging biology are poorly understood. We hypothesize that circulating metabolites studied cross-sectionally with cardiac aging may be associated with cardiovascular changes that distinguish cardiac aging in women.<br /><b>Methods</b><br />A population-based cohort of community men and women without cardiovascular disease from Singapore underwent detailed clinical and echocardiography examinations. Cross-sectional associations between cardiac functional characteristics and metabolomics profiles were examined.<br /><b>Results</b><br />Five hundred sixty-seven adults (48.9% women) participated. Women were younger (72 ± 4.4 years vs 73 ± 4.3 years, p = 0.022), had lower diastolic blood pressures (71 ± 11.0 mmHg vs 76 ± 11.2 mmHg, p < 0.0001, and less likely to have diabetes mellitus (18.0% vs 27.6%, p = 0.013) and smoking (3.8% vs 34.5%, p < 0.001). Body mass indices were similar (24 ± 3.8 kg/m<sup>2</sup> vs 24 ± 3.4 kg/m<sup>2</sup>, p = 0.29), but women had smaller waist circumferences (81 ± 10.1 cm vs 85 ± 9.2 cm, p < 0.001). Women had a significantly higher E/e\' ratios (10.9 ± 3.4 vs 9.9 ± 3.3, p = 0.007) and mitral A peak (0.86 ± 0.2 m/s vs 0.79 ± 0.2 m/s, p < 0.001) than men. Among women, lower E/e\' ratio was associated with higher levels of C16 (OR 1.019, 95%CI 1.002-1.036, p = 0.029), C16:1 (OR 1.06, 95%CI 1.006-1.118, p = 0.028), serine (OR 1.019, 95%CI 1.002-1.036, p = 0.025), and histidine (OR 1.045, 95%CI 1.013-1.078, p = 0.006). Lower mitral A peak was associated with higher levels of histidine (OR 1.039, 95%CI 1.009-1.070, p = 0.011), isoleucine (OR 1.013, 95%CI 1.004-1.021, p = 0.004), and C20 (OR 1.341, 95%CI 1.067-1.684, p = 0.012).<br /><b>Conclusion</b><br />Impairments in diastolic functions were more frequent among older women compared to men, despite lower prevalence of vascular risk factors and preserved cardiac structure. Cardiac aging in women correlated with metabolites involved in fatty acid oxidation and tricyclic acid cycle fuelling.<br /><br />© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.<br /><br /><small>Clin Res Cardiol: 18 Jan 2023; epub ahead of print</small></div>
Ho JS, Wong JJ, Gao F, Wee HN, ... Kovalik JP, Koh AS
Clin Res Cardiol: 18 Jan 2023; epub ahead of print | PMID: 36651997
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<div><h4>Contemporary incidence and predictors of left ventricular thrombus in patients with anterior acute myocardial infarction.</h4><i>Boivin-Proulx LA, Ieroncig F, Demers SP, Nozza A, ... Potter BJ, Marquis-Gravel G</i><br /><b>Background</b><br />The incidence of left ventricular thrombus (LVT) after anterior acute myocardial infarction (AMI) has not been well established in the era of primary percutaneous coronary intervention (pPCI) and potent dual antiplatelet therapy. The objective of this study is to establish the contemporary incidence of LVT in this population, to identify their risk factors, and to examine their association with clinical outcomes.<br /><b>Methods</b><br />A multicenter retrospective cohort study including AMI patients with new-onset antero-apical wall motion abnormalities treated with pPCI between 2009 and 2017 was conducted. The primary outcome was LVT during the index hospitalization. Predictors of LVT were identified using multivariate logistic regression. Net adverse clinical events (NACE), a composite of mortality, myocardial infarction, stroke or transient ischemic attack, systemic thromboembolism or BARC type 3 or 5 bleeding at 6 months were compared between the LVT and no LVT groups.<br /><b>Results</b><br />Among the 2136 patients included, 83 (3.9%) patients developed a LVT during index hospitalization. A lower left ventricular ejection fraction (LVEF) [adjusted odds ratio (aOR) 0.97; 95% confidence intervals (CI) 0.94-0.99] and the degree of worse anterior WMA (aOR 4.34; 95% CI 2.24-8.40) were independent predictors of LVT. A NACE occurred in 5 (5.72 per 100 patient-year) patients in the LVT group and in 127 (6.71 per 100 patient-year) patients in the no LVT group at 6 months [adjusted hazard ratio (aHR): 0.87; 95% CI 0.35-2.14].<br /><b>Conclusions</b><br />The risk of LVT after anterior AMI with new-onset wall motion abnormalities is low, but this complication remains present in the contemporary era of timely pPCI and potent dual antiplatelet therapy .<br /><br />© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.<br /><br /><small>Clin Res Cardiol: 18 Jan 2023; epub ahead of print</small></div>
Boivin-Proulx LA, Ieroncig F, Demers SP, Nozza A, ... Potter BJ, Marquis-Gravel G
Clin Res Cardiol: 18 Jan 2023; epub ahead of print | PMID: 36651998
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<div><h4>Characteristics and outcomes of patients undergoing transcatheter mitral valve replacement with the Tendyne system.</h4><i>Wilde N, Tenaka T, Vij V, Sugiura A, ... Weber M, Zimmer S</i><br /><b>Background</b><br />Transcatheter mitral valve replacement (TMVR) has emerged as alternative to transcatheter edge-to-edge repair (TEER) for treatment of mitral regurgitation (MR); however, the role of TMVR with the Tendyne system among established treatments of MR is not well defined. We assessed characteristics and outcomes of patients treated with the Tendyne system in the current clinical practice.<br /><b>Methods</b><br />We reviewed patients who underwent cardiac computed tomography and were judged eligible for the Tendyne system.<br /><b>Results</b><br />A total of 63 patients were eligible for TMVR with the Tendyne system. Of these, 17 patients underwent TMVR, and 46 were treated by TEER. Patients treated with the Tendyne system were more likely to have a high transmitral pressure gradient and unsuitable mitral valve morphology for TEER than those treated with TEER. TMVR with the Tendyne system reduced the severity of MR to less than 1 + in 94.1% of the patients at discharge and achieved a greater reduction in left ventricular (LV) end-diastolic volume at the 30-day follow-up compared with TEER. In contrast, patients treated with the Tendyne system had a higher 30-day mortality than those treated with TEER, while the mortality between 30 days and one year was comparable between Tendyne and TEER.<br /><b>Conclusions</b><br />Among patients eligible for the Tendyne system, approximately a quarter of the patients underwent TMVR with the Tendyne system, which led substantial reduction of MR and LV reverse remodeling than TEER. In contrast, the 30-day mortality rate was higher after TMVR with the Tendyne compared to TEER.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 16 Jan 2023; epub ahead of print</small></div>
Wilde N, Tenaka T, Vij V, Sugiura A, ... Weber M, Zimmer S
Clin Res Cardiol: 16 Jan 2023; epub ahead of print | PMID: 36645506
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<div><h4>Effectiveness of radiation protection systems in the cardiac catheterization laboratory: a comparative study.</h4><i>Cammann VL, Schweiger V, Cieslik M, Seifert B, ... Templin C, Gotschy A</i><br /><b>Background</b><br />As numbers and complexity of percutaneous coronary interventions are constantly increasing, optimal radiation protection is required to ensure operator safety. Suspended radiation protection systems (SRPS) and protective scatter-radiation absorbing drapes (PAD) are novel methods to mitigate fluoroscopic scattered radiation exposure. The aim of the study was to investigate the effectiveness regarding radiation protection of a SRPS and a PAD in comparison with conventional protection.<br /><b>Methods</b><br />A total of 229 cardiac catheterization procedures with SRPS (N = 73), PAD (N = 82) and standard radiation protection (N = 74) were prospectively included. Real-time dosimeter data were collected from the first operator and the assistant. Endpoints were the cumulative operator exposure relative to the dose area product [standardized operator exposure (SOE)] for the first operator and the assistant.<br /><b>Results</b><br />For the first operator, the SRPS and the PAD significantly decreased the overall SOE compared to conventional shielding by 93.9% and 66.4%, respectively (P < 0.001). The protective effect of the SRPS was significantly higher compared to the PAD (P < 0.001). For the assistant, the SRPS and the PAD provided a not statistically significant reduction compared to conventional shielding in the overall SOE by 38.0% and 30.6%, respectively.<br /><b>Conclusions</b><br />The SRPS and the PAD enhance radiation protection significantly compared to conventional protection. In most clinical scenarios, the protective effect of SRPS is significantly higher than the additional protection provided by the PAD. Comparison of the additional radiation protection provided by protective scatter-radiation absorbing drapes (PAD) and the suspended radiation protection system (SRPS) system over standard protection with lead aprons.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 16 Jan 2023; epub ahead of print</small></div>
Cammann VL, Schweiger V, Cieslik M, Seifert B, ... Templin C, Gotschy A
Clin Res Cardiol: 16 Jan 2023; epub ahead of print | PMID: 36646858
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<div><h4>Trans-fatty acid blood levels of industrial but not natural origin are associated with cardiovascular risk factors in patients with HFpEF: a secondary analysis of the Aldo-DHF trial.</h4><i>Lechner K, Bock M, von Schacky C, Scherr J, ... Duvinage A, Edelmann F</i><br /><b>Background</b><br />Industrially processed trans-fatty acids (IP-TFA) have been linked to altered lipoprotein metabolism, inflammation and increased NT-proBNP. In patients with heart failure with preserved ejection fraction (HFpEF), associations of TFA blood levels with patient characteristics are unknown.<br /><b>Methods</b><br />This is a secondary analysis of the Aldo-DHF-RCT. From 422 patients, individual blood TFA were analyzed at baseline in n = 404 using the HS-Omega-3-Index<sup>®</sup> methodology. Patient characteristics were: 67 ± 8 years, 53% female, NYHA II/III (87/13%), ejection fraction ≥ 50%, E/e\' 7.1 ± 1.5; NT-proBNP 158 ng/L (IQR 82-298). A principal component analysis was conducted but not used for further analysis as cumulative variance for the first two PCs was low. Spearman\'s correlation coefficients as well as linear regression analyses, using sex and age as covariates, were used to describe associations of whole blood TFA with metabolic phenotype, functional capacity, echocardiographic markers for LVDF and neurohumoral activation at baseline and after 12 months.<br /><b>Results</b><br />Blood levels of the naturally occurring TFA C16:1n-7t were inversely associated with dyslipidemia, body mass index/truncal adiposity, surrogate markers for non-alcoholic fatty liver disease and inflammation at baseline/12 months. Conversely, IP-TFA C18:1n9t, C18:2n6tt and C18:2n6tc were positively associated with dyslipidemia and isomer C18:2n6ct with dysglycemia. C18:2n6tt and C18:2n6ct were inversely associated with submaximal aerobic capacity at baseline/12 months. No significant association was found between TFA and cardiac function.<br /><b>Conclusions</b><br />In HFpEF patients, higher blood levels of IP-TFA, but not naturally occurring TFA, were associated with dyslipidemia, dysglycemia and lower functional capacity. Blood TFAs, in particular C16:1n-7t, warrant further investigation as prognostic markers in HFpEF. Higher blood levels of industrially processed TFA, but not of the naturally occurring TFA C16:1n-7t, are associated with a higher risk cardiometabolic phenotype and prognostic of lower aerobic capacity in patients with HFpEF.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 14 Jan 2023; epub ahead of print</small></div>
Lechner K, Bock M, von Schacky C, Scherr J, ... Duvinage A, Edelmann F
Clin Res Cardiol: 14 Jan 2023; epub ahead of print | PMID: 36640187
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<div><h4>CTA-determined tricuspid annular dilatation is associated with persistence of tricuspid regurgitation after transcatheter aortic valve replacement.</h4><i>Löw K, Steffen J, Theiss H, Orban M, ... Braun D, Deseive S</i><br /><b>Aim</b><br />The aim of this study was to analyse the predictive value of CTA-determined tricuspid annular dilatation (TAD) on the persistence of tricuspid regurgitation (TR) in patients undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS) and concomitant at least moderate TR.<br /><b>Methods and results</b><br />288 consecutive patients treated with TAVR due to severe AS and concomitant at least moderate TR at baseline were included in the analysis. As cutoff for TAD, the median value of the CTA-determined, to the body surface area-normalized tricuspid annulus diameter (25.2 mm/m<sup>2</sup>) was used. TAD had no impact on procedural characteristics or outcomes, including procedural death and technical or device failure according to the Valve Academic Research Consortium 3 criteria. However, the primary outcome of the study-TR persistence after TAVR was significantly more frequent in patients with compared to patients without TAD (odds ratio 2.60, 95% confidence interval 1.33-5.16, p < 0.01). Multivariable logistic regression analysis, adjusting for clinical and echocardiographic baseline characteristics, which are known to influence aetiology or severity of TR, confirmed TAD as an independent predictor of TR persistence after TAVR (adjusted odds ratio 2.30, 95% confidence interval 1.20-4.46, p = 0.01). Moreover, 2 year all-cause mortality was significantly higher in patients with persistence or without change of TR compared to patients with TR improvement (log-rank p < 0.01).<br /><b>Conclusion</b><br />In patients undergoing TAVR for severe AS and concomitant at least moderate TR at baseline, TAD is a predictor of TR persistence, which is associated with increased 2-year all-cause mortality.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 13 Jan 2023; epub ahead of print</small></div>
Löw K, Steffen J, Theiss H, Orban M, ... Braun D, Deseive S
Clin Res Cardiol: 13 Jan 2023; epub ahead of print | PMID: 36637479
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<div><h4>Intensive lipid-lowering therapy for early achievement of guideline-recommended LDL-cholesterol levels in patients with ST-elevation myocardial infarction (\"Jena auf Ziel\").</h4><i>Makhmudova U, Samadifar B, Maloku A, Haxhikadrija P, ... Schulze PC, Weingärtner O</i><br /><b>Background:</b><br/>and aims</b><br />Currently, less than 20% of patients at very high-risk achieve ESC/EAS dyslipidemia guideline-recommended LDL-C target levels in Europe. \"Jena auf Ziel-JaZ\" is a prospective cohort study in which early combination therapy with atorvastatin 80 mg and ezetimibe 10 mg was initiated on admission in patients with ST-elevation myocardial infarction (STEMI) and lipid-lowering therapy was escalated during follow-up with bempedoic acid and PCSK9 inhibitors to achieve recommended LDL-C targets in all patients. Moreover, we evaluated side-effects of lipid-lowering therapy.<br /><b>Methods</b><br />Patients admitted with STEMI at Jena University Hospital were started on atorvastatin 80 mg and ezetimibe 10 mg on admission. Patients were followed for EAS/ESC LDL-C target achievement during follow-up.<br /><b>Results</b><br />A total of 85 consecutive patients were enrolled in the study. On discharge, 32.9% achieved LDL-C targets on atorvastatin 80 mg and ezetimibe 10 mg. After 4-6 weeks, 80% of all patients on atorvastatin 80 mg and ezetimibe started at the index event were on ESC/EAS LDL-C targets. In 20%, combined lipid-lowering therapy was escalated with either bempedoic acid or PCSK9 inhibitors. All patients achieved LDL-C levels of or below 55 mg/dL during follow-up on triple lipid-lowering therapy. Combined lipid-lowering therapy was well-tolerated with rare side effects.<br /><b>Conclusions</b><br />Early combination therapy with a high-intensity statin and ezetimibe and escalation of lipid-lowering therapy with either bempedoic acid or PCSK9 inhibitors gets potentially all patients with STEMI on recommended ESC/EAS LDL-C targets without significant side effects.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 05 Jan 2023; epub ahead of print</small></div>
Makhmudova U, Samadifar B, Maloku A, Haxhikadrija P, ... Schulze PC, Weingärtner O
Clin Res Cardiol: 05 Jan 2023; epub ahead of print | PMID: 36602598
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<div><h4>Prognostic impact of resting full-cycle ratio and diastolic non-hyperemic pressure ratios in patients with deferred revascularization.</h4><i>Halbach M, Ameskamp C, Mauri V, Ernst A, ... Adam M, Wienemann H</i><br /><b>Background</b><br />Non-hyperemic pressure ratios (NHPRs) like resting full-cycle ratio (RFR), diastolic pressure ratio during entire diastole (dPR[entire]) and diastolic pressure ratio during wave-free period (dPR[WFP]) are increasingly used to guide revascularization. The effect of NHPRs on mid-term prognosis has not been well established.<br /><b>Objective</b><br />We investigated the prognostic implications of NHRPs in patients whose revascularization was deferred based on fractional flow reserve (FFR) in a single-centre population.<br /><b>Methods</b><br />NHPRs and FFR were calculated offline from pressure tracings by an independent core laboratory. Follow-up data were acquired through records of hospital visits or telephone interviews. The primary outcome was a vessel-oriented composite outcome (VOCO) (a composite of cardiac death, vessel-related myocardial infarction, and ischemia-driven revascularization) in deferred vessels at 2 years.<br /><b>Results</b><br />316 patients with 377 deferred lesions were analysed. Discordance of NHPRs and FFR was found in 13.0-18.3% of lesions. The correlation coefficient between NHPRs was 0.99 (95% confidence interval 0.99-1.00). At 2 years, VOCO occurred in 19 lesions (5.0%). Estimated glomerular filtration rate < 30 mL/min/1.73 m<sup>2</sup> [hazard ratio (HR) 5.7, p = 0.002], previous myocardial infarction (HR 3.3, p = 0.018), diabetes (HR 2.7, p = 0.042), RFR ≤ 0.89 (HR 2.7, p = 0.041) and dPR[WFP] ≤ 0.89 (HR 2.7, p = 0.049) were associated with higher incidence of VOCO at 2 years in the univariable analysis. A non-significant trend was found for dPR[entire] (HR 1.9, p = 0.26).<br /><b>Conclusion</b><br />A positive RFR or dPR[WFP] were associated with a worse prognosis in deferred lesions, suggesting that the use of NHPRs in addition to FFR may improve risk estimation.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 05 Jan 2023; epub ahead of print</small></div>
Halbach M, Ameskamp C, Mauri V, Ernst A, ... Adam M, Wienemann H
Clin Res Cardiol: 05 Jan 2023; epub ahead of print | PMID: 36602599
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<div><h4>Cardiovascular and renal effects of SGLT2 inhibitor initiation in acute heart failure: a meta-analysis of randomized controlled trials.</h4><i>Carvalho PEP, Veiga TMA, Simões E Silva AC, Gewehr DM, ... Nasi G, Cardoso R</i><br /><b>Background</b><br />We sought to compare cardiovascular outcomes, renal function, and diuresis in patients receiving standard diuretic therapy for acute heart failure (AHF) with or without the addition of SGLT2i.<br /><b>Methods and results</b><br />Systematic search of three electronic databases identified nine eligible randomized controlled trials involving 2,824 patients. The addition of SGLT2i to conventional therapy for AHF reduced all-cause death (odds ratio [OR] 0.75; 95% CI 0.56-0.99; p = 0.049), readmissions for heart failure (HF) (OR 0.54; 95% CI 0.44-0.66; p < 0.001), and the composite of cardiovascular death and readmissions for HF (hazard ratio 0.71; 95% CI 0.60-0.84; p < 0.001). Furthermore, SGLT2i increased mean daily urinary output in liters (mean difference [MD] 0.45; 95% CI 0.03-0.87; p = 0.035) and decreased mean daily doses of loop diuretics in mg of furosemide equivalent (MD -34.90; 95% CI [- 52.58, - 17.21]; p < 0.001) without increasing the incidence worsening renal function (OR 0.75; 95% CI 0.43-1.29; p = 0.290).<br /><b>Conclusion</b><br />SGLT2i addition to conventional diuretic therapy reduced all-cause death, readmissions for HF, and the composite of cardiovascular death or readmissions for HF. Moreover, SGLT2i was associated with a higher volume of diuresis with a lower dose of loop diuretics.<br /><br />© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.<br /><br /><small>Clin Res Cardiol: 02 Jan 2023; epub ahead of print</small></div>
Carvalho PEP, Veiga TMA, Simões E Silva AC, Gewehr DM, ... Nasi G, Cardoso R
Clin Res Cardiol: 02 Jan 2023; epub ahead of print | PMID: 36592186
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<div><h4>Characteristics and outcomes of angiovac-assisted debulking of intracardiac masses, thrombi, and endocarditis.</h4><i>Patail H, Cheema M, McKay R, Ingrassia J</i><br /><b>Background</b><br />Traditional management for right-sided infective endocarditis and other adherent masses centers around balancing the risks and benefits of open surgical removal against medical therapy.<br /><b>Methods</b><br />Single-center study analysis of 19 patients who underwent vacuum-assisted debulking and/or en bloc removal of right-sided infective endocarditis and other adherent masses between September 2017 and November 2021. Clinical outcomes during the perioperative period, postoperative period, hospital course, and post-discharge were analyzed.<br /><b>Results</b><br />We included 12 male and 7 female patients with an average age 47.4 ± 16.8. Relevant risk factors included 47.4% of patients with active intravenous drug use (IVDU), 21.1% of patients with a history of permanent pacemaker (PPM) or implantable cardioverter-defibrillator (ICD), and 5.3% of prior malignancy with mediastinal radiation. 31.6% of patients had documented right-sided masses from a non-infectious etiology, while 68.4% of patients were noted to have right-sided infective endocarditis (RSIE). All patients were found to have large, mobile masses or vegetations at high risk for embolization to the pulmonary vasculature. Average in-hospital length of stay was 17.8 ± 12.2 days, blood cultures cleared postoperatively in 8.9 ± 7.3 days, periprocedural mortality was 0%, subsequent open surgical valvular repair during the same admission was 5.3%, and in-hospital mortality was 5.3%. Within 6 weeks of follow-up, 15.8% of patients were readmitted for recurrence of bacteremia, 10.5% of patients were found to have new pulmonary embolism, and 15.8% of patients underwent open surgical valvular repair. Total death after 1-year and 2-years was 15.8% and 5.3%, respectively. Recurrence of bacteremia was 21.1% within 1-year.<br /><b>Conclusion</b><br />AngioVac is a viable therapeutic strategy for select patients with intravascular and intracardiac right-sided masses including thrombi, emboli, or infective masses such as endocarditis.<br /><br />© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.<br /><br /><small>Clin Res Cardiol: 30 Dec 2022; epub ahead of print</small></div>
Patail H, Cheema M, McKay R, Ingrassia J
Clin Res Cardiol: 30 Dec 2022; epub ahead of print | PMID: 36583764
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<div><h4>Myocarditis mortality with and without COVID-19: insights from a national registry.</h4><i>Bemtgen X, Kaier K, Rilinger J, Rottmann F, ... Wengenmayer T, Staudacher DL</i><br /><b>Background</b><br />Myocarditis in context of a SARS-CoV-2 infection is vividly discussed in the literature. Real-world data however are sparse, and relevance of the myocarditis diagnosis to outcome in coronavirus disease (COVID-19) is unclear.<br /><b>Patients and methods</b><br />Retrospective analysis of 75,304 patients hospitalized in Germany with myocarditis between 2007 and 2020 is reported by DESTATIS. Patients hospitalized between 01/2016 and 12/2019 served as reference cohort for the COVID-19 patients hospitalized in 2020.<br /><b>Results</b><br />A total of 75,304 patients were hospitalized between 2007 and 2020 (age 42.5 years, 30.1% female, hospital mortality 2.4%). In the reference cohort, 24,474 patients (age 42.8 years, 29.5% female, hospital mortality 2.2%) were registered. In 2020, annual myocarditis hospitalizations dropped by 19.6% compared to reference (4921 vs. 6119 annual hospitalization), of which 443/4921 (9.0%) were connected to COVID-19. In 2020, hospital mortality of myocarditis in non-COVID-19 patients increased significantly compared to reference (2.9% vs. 2.2%, p = 0.008, OR 1.31, 95% CI 1.08-1.60). In COVID-19 myocarditis, hospital mortality was even higher compared to reference (13.5% vs. 2.2%, p < 0.001, OR 6.93, 95% CI 5.18-9.18).<br /><b>Conclusion</b><br />The burden of patients with myocarditis and COVID-19 in 2020 was low. Hospital mortality was more than sixfold higher in patients with myocarditis and COVID-19 compared to those with myocarditis but without COVID-19.<br /><br />© 2022. The Author(s).<br /><br /><small>Clin Res Cardiol: 24 Dec 2022; epub ahead of print</small></div>
Bemtgen X, Kaier K, Rilinger J, Rottmann F, ... Wengenmayer T, Staudacher DL
Clin Res Cardiol: 24 Dec 2022; epub ahead of print | PMID: 36565377
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<div><h4>Recovery of right ventricular function after intermediate-risk pulmonary embolism: results from the multicentre Pulmonary Embolism International Trial (PEITHO)-2.</h4><i>Mavromanoli AC, Barco S, Ageno W, Bouvaist H, ... Konstantinides SV, PEITHO-2 Investigators</i><br /><b>Background</b><br />Right ventricular (RV) function plays a critical role in the pathophysiology and acute prognosis of pulmonary embolism (PE). We analyzed the temporal changes of RV function in the cohort of a prospective multicentre study investigating if an early switch to oral anticoagulation in patients with intermediate-risk PE is effective and safe.<br /><b>Methods</b><br />Echocardiographic and laboratory examinations were performed at baseline (PE diagnosis), 6 days and 6 months. Echocardiographic parameters were classified into categories representing RV size, RV free wall/tricuspid annulus motion, RV pressure overload and right atrial (RA)/central venous pressure.<br /><b>Results</b><br />RV dysfunction based on any abnormal echocardiographic parameter was present in 84% of patients at baseline. RV dilatation was the most frequently abnormal finding (40.6%), followed by increased RA/central venous pressure (34.6%), RV pressure overload (32.1%), and reduced RV free wall/tricuspid annulus motion (20.9%). As early as day 6, RV size remained normal or improved in 260 patients (64.7%), RV free wall/tricuspid annulus motion in 301 (74.9%), RV pressure overload in 297 (73.9%), and RA/central venous pressure in 254 (63.2%). At day 180, the frequencies slightly increased. The median NT-proBNP level decreased from 1448 pg/ml at baseline to 256.5 on day 6 and 127 on day 180.<br /><b>Conclusion</b><br />In the majority of patients with acute intermediate-risk PE switched early to a direct oral anticoagulant, echocardiographic parameters of RV function normalised within 6 days and remained normal throughout the first 6 months. Almost one in four patients, however, continued to have evidence of RV dysfunction over the long term.<br /><br />© 2022. The Author(s).<br /><br /><small>Clin Res Cardiol: 21 Dec 2022; epub ahead of print</small></div>
Mavromanoli AC, Barco S, Ageno W, Bouvaist H, ... Konstantinides SV, PEITHO-2 Investigators
Clin Res Cardiol: 21 Dec 2022; epub ahead of print | PMID: 36539534
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<div><h4>Daily life and psychosocial functioning of adults with congenital heart disease: a 40-53 years after surgery follow-up study.</h4><i>Pelosi C, Kauling RM, Cuypers JAAE, van den Bosch AE, ... Legerstee JS, Roos-Hesselink JW</i><br /><b>Introduction</b><br />Nowadays, more than 90% of patients with congenital heart disease (CHD) reach adulthood. However, knowledge about their psychosocial functioning is limited.<br /><b>Methods</b><br />Longitudinal cohort study of patients (n = 204, mean age: 50 years, 46.1% female) who were operated during childhood (< 15 years) between 1968 and 1980 for one of the following diagnoses: atrial septal defect, ventricular septal defect, pulmonary stenosis, tetralogy of Fallot or transposition of the great arteries. Psychosocial functioning was measured every 10 years, using standardized and validated questionnaires. Results were compared with the general Dutch population and over time.<br /><b>Results</b><br />After a median follow-up of 45 [40-53] years adults with CHD had a significantly lower educational level, occupation level and employment rate, but better health-related quality of life and emotional functioning compared with normative data. Patients with moderate/severe defects reported significantly more self-perceived physical restrictions and lack of physical strength due to their CHD. Compared to 2011, in 2021 patients considered their CHD as more severe and they felt more often disadvantaged.<br /><b>Conclusions</b><br />Overall, despite a lower education, occupation level and employment rate, our sample of patients with CHD had a positive perception of their life and  their psychosocial functioning was even better than the norm. Although the quality of life was very good, their view on their disease was more pessimistic than 10 years ago, especially for patients with moderate/severe CHD.<br /><br />© 2022. The Author(s).<br /><br /><small>Clin Res Cardiol: 19 Dec 2022:1-11; epub ahead of print</small></div>
Pelosi C, Kauling RM, Cuypers JAAE, van den Bosch AE, ... Legerstee JS, Roos-Hesselink JW
Clin Res Cardiol: 19 Dec 2022:1-11; epub ahead of print | PMID: 36534138
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<div><h4>Prediction of incident atrial fibrillation in post-stroke patients using machine learning: a French nationwide study.</h4><i>Bisson A, Lemrini Y, El-Bouri W, Bodin A, ... Lip GYH, Fauchier L</i><br /><b>Background</b><br />Targeting ischemic strokes patients at risk of incident atrial fibrillation (AF) for prolonged cardiac monitoring and oral anticoagulation remains a challenge. Clinical risk scores have been developed to predict post-stroke AF with suboptimal performances. Machine learning (ML) models are developing in the field of AF prediction and may be used to discriminate post-stroke patients at risk of new onset AF. This study aimed to evaluate ML models for the prediction of AF and to compare predictive ability to usual clinical scores.<br /><b>Methods</b><br />Based on a French nationwide cohort of 240,459 ischemic stroke patients without AF at baseline from 2009 to 2012, ML models were trained on a train set and the best model was selected to be evaluate on the test set. Discrimination of the best model was evaluated using the C index. We finally compared our best model with previously described clinical scores.<br /><b>Results</b><br />During a mean follow-up of 7.9 ± 11.5 months, 14,095 patients (mean age 77.6 ± 10.6; 50.3% female) developed incident AF. After training, the best ML model selected was a deep neural network with a C index of 0.77 (95% CI 0.76-0.78) on the test set. Compared to traditional clinical scores, the selected model was statistically significantly superior to the CHA<sub>2</sub>DS<sub>2</sub>-VASc score, Framingham risk score, HAVOC score and C<sub>2</sub>HEST score (P < 0.0001). The ability to predict AF was improved as shown by net reclassification index increase (P < 0.0001) and decision curve analysis.<br /><b>Conclusions</b><br />ML algorithms predict incident AF post-stroke with a better ability than previously developed clinical scores. AF: atrial fibrillation; DNN: deep neural network; IS: ischemic stroke; KNN: K-nearest neighbors; LR: logistic regression; RFC: random forest classifier; XGBoost: extreme gradient boosting.<br /><br />© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.<br /><br /><small>Clin Res Cardiol: 17 Dec 2022; epub ahead of print</small></div>
Bisson A, Lemrini Y, El-Bouri W, Bodin A, ... Lip GYH, Fauchier L
Clin Res Cardiol: 17 Dec 2022; epub ahead of print | PMID: 36527472
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<div><h4>Impact of transcatheter edge-to-edge mitral valve repair on central sleep apnoea.</h4><i>Paulus MG, Liedtke T, Hamerle M, Schach C, ... Unsöld B, Meindl C</i><br /><b>Aims</b><br />Sleep-disordered breathing (SDB) and its subtype central sleep apnoea (CSA) are highly prevalent in patients with heart failure and associated with worse prognosis. Whereas pharmacological therapy of heart failure has been shown to ameliorate CSA, results from previous studies on the effect of mitral regurgitation therapy on SDB are contradicting. The aim of this study was to assess the impact of transcatheter edge-to-edge mitral valve repair (TEER) on prevalence and severity of CSA.<br /><b>Methods and results</b><br />We enrolled 47 patients undergoing TEER for symptomatic mitral regurgitation in a prospective study. Secondary mitral regurgitation and left ventricular ejection fraction < 50% were present in 79% and 68% of patients, respectively. Respiratory polygraphy was performed before TEER in a compensated condition and four weeks after the procedure. 34 patients completed the follow-up. At baseline, 19 (56%) patients showed moderate-to-severe SDB, of whom 13 (68%) were classified as CSA. Both apnoea-hypopnoea index and percentage of recorded time spent in Cheyne-Stokes respiration strongly decreased from baseline to follow-up (median [IQR] 16 [7-30] vs. 7 [4-15] /h, p = 0.007; 6 [0-34] vs. 0 [0-8] %, p = 0.008). Median relative reduction of central apnoea index was 75% (p = 0.023), while obstructive apnoea index did not change significantly. Increase in stroke volume after TEER and high systolic pulmonary artery pressure at baseline predicted a > 50% reduction of both Apnoea-hypopnoea index and Cheyne-Stokes respiration.<br /><b>Conclusion</b><br />TEER is associated with a significant short-term reduction of CSA and Cheyne-Stokes respiration in high-risk patients, strengthening its value as an effective treatment option for advanced heart failure.<br /><br />© 2022. The Author(s).<br /><br /><small>Clin Res Cardiol: 12 Dec 2022; epub ahead of print</small></div>
Paulus MG, Liedtke T, Hamerle M, Schach C, ... Unsöld B, Meindl C
Clin Res Cardiol: 12 Dec 2022; epub ahead of print | PMID: 36507943
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<div><h4>RAS inhibitors and renal and general mortality in patients with heart failure supported by left ventricular assist devices: a registry study.</h4><i>Lombardi G, Gambaro A, Ribichini FL, Ferraro PM, Gambaro G</i><br /><b>Background</b><br />The aim of our study was to analyze the association between renin-angiotensin system inhibitor (RASi) therapy and renal outcomes and mortality in patients with heart failure (HF) supported by left ventricular assist device (LVAD) using a large, nationwide prospective cohort. To date, no studies have comprehensively analyzed the association between RASi and renal outcomes and mortality in patients with HF supported by LVAD.<br /><b>Methods</b><br />We performed a retrospective observational study on LVAD patients in the Interagency Registry for Mechanically Assisted Circulatory Support. The main outcome was a composite of renal event and all-cause mortality. Secondary outcomes were the individual components of the composite outcome. A renal event was defined as a composite of doubling serum creatinine, eGFR decrease ≥ 40%, or need for dialysis. The exposure of interest was RASi therapy, updated during follow-up. Cox regression models adjusted for potential confounders were used to estimate the association between time-updated RASi therapy and the outcomes of interest.<br /><b>Results</b><br />The analysis included 6448 patients. During a median follow-up of 12.7 months (IQR 19.8 months), 1632 patients developed the composite outcome. RASi therapy was associated with a lower risk of developing the composite outcome (HR 0.61, 95% CI 0.55, 0.68, P < 0.001). A significant association was confirmed between RASi therapy and renal outcomes (HR 0.74, 95% CI 0.61, 0.89, P = 0.002) and all-cause mortality (HR 0.56, 95% CI 0.50, 0.63, P < 0.001).<br /><b>Conclusions</b><br />Our data suggest a beneficial role of RASi therapy on renal function and all-cause mortality in patients with HF supported by LVAD.<br /><br />© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.<br /><br /><small>Clin Res Cardiol: 02 Dec 2022; epub ahead of print</small></div>
Lombardi G, Gambaro A, Ribichini FL, Ferraro PM, Gambaro G
Clin Res Cardiol: 02 Dec 2022; epub ahead of print | PMID: 36459185
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<div><h4>Predictive value of the Fibrosis-4 index in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement.</h4><i>Sudo M, Shamekhi J, Sedaghat A, Aksoy A, ... Tiyerili V, Al-Kassou B</i><br /><b>Background</b><br />Liver dysfunction is associated with an increased risk of mortality after cardiac interventions. The Fibrosis-4 (FIB-4 index), a marker of hepatic fibrosis, has been associated with a worse prognosis in heart failure. The prognostic relevance of the index in patients undergoing transcatheter aortic valve replacement (TAVR) is unknown. The aim of this study was to evaluate the clinical implications associated with the FIB-4 index in patients undergoing TAVR.<br /><b>Methods</b><br />Between May 2012 and June 2019, 941 patients undergoing TAVR were stratified into a low or high FIB-4 index group, based on a cutoff value that was determined according to a receiver operating characteristic curve predicting 1-year all-cause mortality.<br /><b>Results</b><br />Patients with a high FIB-4 index (n = 480), based on the cutoff value of 1.82, showed higher rates of pulmonary hypertension (43.8% vs. 31.8%, p < 0.01), right-ventricular systolic dysfunction (29.5% vs. 19.2%, p < 0.01) and larger inferior vena cava diameter (1.6 ± 0.6 cm vs. 1.3 ± 0.6 cm, p < 0.01) than patients with a low FIB-4 index (n = 461). Furthermore, a high FIB-4 index was associated with a significantly higher cumulative 1-year all-cause mortality (17.5% vs. 10.2%, p < 0.01) and non-cardiovascular mortality (12.1% vs. 2.5%, p < 0.01), compared to a low FIB-4 index. Multivariable analysis revealed that a high FIB-4 index was independently associated with all-cause mortality (HR: 1.75 [95% CI: 1.18-2.59], p < 0.01).<br /><b>Conclusions</b><br />A high FIB-4 index is associated with right-sided heart overload and an increased risk of mortality in patients undergoing TAVR. The FIB-4 index may be useful as an additional predictor of outcomes in these patients.<br /><br />© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.<br /><br /><small>Clin Res Cardiol: 01 Dec 2022; 111:1367-1376</small></div>
Sudo M, Shamekhi J, Sedaghat A, Aksoy A, ... Tiyerili V, Al-Kassou B
Clin Res Cardiol: 01 Dec 2022; 111:1367-1376 | PMID: 35852581
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<div><h4>Bioprosthetic valve dysfunction and failure after TAVI in bicuspid aortic valve stenosis during one-year follow-up according to VARC-3.</h4><i>Veulemans V, Nuyens P, Goh S, Maier O, ... de Backer O, Zeus T</i><br /><b>Background</b><br />Transcatheter aortic valve implantation (TAVI) in bicuspid aortic valve (BAV) stenosis has become more frequent in the last years. This may pose challenges for long-time valve durability. Therefore, we aimed to evaluate the prevalence of bioprosthetic valve dysfunction (BVD) with the newest-generation devices in BAV stenosis up to one-year follow-up (FU).<br /><b>Methods</b><br />The primary endpoint was defined as the prevalence of BVD during the first procedural year according to Valve Academic Research Consortium (VARC)-3 criteria. Secondary endpoints were defined as failure in device success and clinical endpoints according to VARC-3.<br /><b>Results</b><br />A total of 107 patients were included. Of these, 34 subjects (31.8%) met the criteria for BVD during a mean FU of 263 ± 180 days, of which 20.2% were already documented after thirty days. Device success after one year was lower in the + BVD cohort (57.6% vs. 98.7%, p < 0.0001*). The rates of structural valve deterioration were 6.5%, non-structural valve deterioration (NSVD) 17.8%, subclinical leaflet thickening 10.3%, and endocarditis 0.9%. NSVD was foremost triggered by patient prosthesis mismatch in balloon-expandable valves. Hemodynamic valve deterioration stage 1 and 2 was confirmed in 16.8% of + BVD patients, while stage 1 and 3 bioprosthetic valve failure occurred in 1.9%. There was no impact of BVD on mortality.<br /><b>Conclusion</b><br />There is critical evidence of early BVD after TAVI in BAV during one-year FU in one-third of patients, also lowering device success. The most frequently observed bioprosthetic valve dysfunction was NSVD due to patient prosthesis mismatch following TAVI with a balloon-expandable valve.<br /><br />© 2022. The Author(s).<br /><br /><small>Clin Res Cardiol: 01 Dec 2022; 111:1358-1366</small></div>
Veulemans V, Nuyens P, Goh S, Maier O, ... de Backer O, Zeus T
Clin Res Cardiol: 01 Dec 2022; 111:1358-1366 | PMID: 35767098
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<div><h4>The impact of bicuspid aortic valve morphology on von Willebrand factor function in patients with severe aortic stenosis and its change after TAVI.</h4><i>Roth N, Heidel C, Xu C, Hubauer U, ... Jungbauer C, Debl K</i><br /><b>Background</b><br />Aortic stenosis (AS) can cause acquired von Willebrand syndrome (AVWS) and valve replacement has been shown to lead to von Willebrand factor (vWF) recovery. The aim of the current study was to investigate the prevalence of AVWS in different severe AS phenotypes and its course after transcatheter aortic valve implantation (TAVI).<br /><b>Methods</b><br />143 patients with severe AS undergoing TAVI were included in the study. vWF function was assessed at baseline, 6 and 24 h after TAVI. AVWS was defined as a reduced vWF:Ac/Ag ratio ≤ 0.7. Phenotypes were classified by tricuspid (TAV) and bicuspid (BAV) valve morphology, mean transvalvular gradient (P<sub>mean</sub>), stroke volume index (SVI), ejection fraction (EF) and indexed effective orifice area (iEOA).<br /><b>Results</b><br />AVWS was present in 36 (25.2%) patients before TAVI. vWF:Ac/Ag ratio was significantly lower in high gradient compared to low-gradient severe AS [0.78 (IQR 0.67-0.86) vs. 0.83 (IQR 0.74-0.93), p < 0.05] and in patients with BAV compared to TAV [0.70 (IQR 0.63-0.78) vs. 0.81 (IQR 0.71-0.89), p < 0.05]. Normalization of vWF:Ac/Ag ratio was achieved in 61% patients 24 h after TAVI. As in the overall study cohort, vWF:Ac/Ag ratio increased significantly in all severe AS subgroups 6 h after TAVI (each p < 0.05). Regarding binary logistic regression analysis, BAV was the only significant predictor for AVWS.<br /><b>Conclusions</b><br />BAV morphology is a strong predictor for AVWS in severe AS. TAVI restores vWF function in most patients with severe AS independently of AS phenotype and valve morphology.<br /><br />© 2022. The Author(s).<br /><br /><small>Clin Res Cardiol: 01 Dec 2022; 111:1348-1357</small></div>
Roth N, Heidel C, Xu C, Hubauer U, ... Jungbauer C, Debl K
Clin Res Cardiol: 01 Dec 2022; 111:1348-1357 | PMID: 35838799
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<div><h4>Concomitant mitral regurgitation in patients with low-gradient aortic stenosis: an analysis from the German Aortic Valve Registry.</h4><i>Alushi B, Ensminger S, Herrmann E, Balaban Ü, ... Frerker C, Lauten A</i><br /><b>Background</b><br />Patients with severe aortic stenosis (AS) frequently presented mitral regurgitation (MR), which may interfere with the standard echocardiographic measurements of mean pressure gradient (MPG), flow velocity, and aortic valve area (AVA).<br /><b>Aims</b><br />Herein we investigated the prevalence and severity of MR in patients with severe AS and its role on the accuracy of the standard echocardiographic parameters of AS quantification.<br /><b>Methods</b><br />Of all patients with severe AS undergoing transcatheter or surgical aortic valve replacement enrolled in the German Aortic Registry from 2011 to 2017, 119,641 were included in this study. The population was divided based on the values of left ventricular ejection fraction ([LVEF] > 50%, LVEF 31-50%, and LVEF ≤ 30%] and AVA (0.80 to ≤ 1.00 cm<sup>2</sup>, 0.60 to < 0.80 cm<sup>2</sup>, 0.40 to < 0.60 cm<sup>2</sup>, and 0.20 to < 0.40 cm<sup>2</sup>).<br /><b>Results</b><br />Overall, 77,890 (65%) patients with mild to-moderate and 4262 (4%) with severe MR were compared with 37,489 (31%) patients without MR. Patients with mild-to-moderate and severe MR presented significantly lower mPG (ΔmPG [95%CI] - 1.694 mmHg [- 2.123 to - 1.265], p < 0.0001 and - 6.954 mmHg [- 7.725 to - 6.183], p < 0.0001, respectively), that increased with LVEF impairment. Conversely, AVA did not differ (severe versus no MR: ΔAVA [95%CI]: - 0.007cm<sup>2</sup> [- 0.023 to 0.009], p = 0.973). Increasing MR severity was associated with significant mPG reduction throughout all AVA strata, causing a low-gradient pattern, that manifested since the early stages of severe AS (LVEF > 50%: AVA 0.80 to 1.00 cm<sup>2</sup>; LVEF 31-50%: AVA 0.60 to 0.80 cm<sup>2</sup>).<br /><b>Conclusions</b><br />In patients with severe AS, concomitant MR is common, contributes to the onset of a low-gradient AS pattern, and affects the diagnostic accuracy of flow-dependent AVA measurements. In this setting, a multimodality, AVA-centric approach should be implemented. In patients with severe aortic stenosis, concomitant mitral regurgitation contributes to the onset of a low-gradient pattern, warranting a multimodality, and AVA-centric diagnostic approach.<br /><br />© 2022. The Author(s).<br /><br /><small>Clin Res Cardiol: 01 Dec 2022; 111:1377-1386</small></div>
Alushi B, Ensminger S, Herrmann E, Balaban Ü, ... Frerker C, Lauten A
Clin Res Cardiol: 01 Dec 2022; 111:1377-1386 | PMID: 35984497
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<div><h4>End-stage renal disease, calcification patterns and clinical outcomes after TAVI.</h4><i>Grundmann D, Linder M, Goßling A, Voigtländer L, ... Conradi L, Seiffert M</i><br /><b>Background</b><br />Patients with chronic hemodialysis due to end-stage renal disease (ESRD) or severely impaired kidney function (CKD) constitute a relevant share of patients undergoing trans-catheter aortic valve implantation (TAVI). However, data on specific challenges and outcomes remain limited.<br /><b>Aim</b><br />We aimed to characterize this patient population, evaluate clinical results and assess the significance of calcification patterns.<br /><b>Methods</b><br />This retrospective single-center analysis evaluated 2,712 TAVI procedures (2012-2019) according to baseline renal function: GFR < 30 ml/min/1.73m<sup>2</sup> (CKD; n = 210), chronic hemodialysis (ESRD; n = 119) and control (CTRL; n = 2383). Valvular and vascular calcification patterns were assessed from contrast-enhanced multi-detector computed tomography. Outcomes were evaluated in accordance with the VARC-2 definitions.<br /><b>Results</b><br />Operative risk was higher in ESRD and CKD vs. CTRL (STS-score 8.4% and 7.6% vs. 3.9%, p < 0.001) and patients with ESRD had more severe vascular calcifications (49.1% vs. 33.9% and 29.0%, p < 0.01). Immediate procedural results were similar but non-procedure-related major/life-threatening bleeding was higher in ESRD and CKD (5.0% and 5.3% vs. 1.6%, p < 0.01). 3-year survival was impaired in patients with ESRD and CKD (33.3% and 35.3% vs. 65.4%, p < 0.001). Multivariable analysis identified ESRD (HR 1.60), CKD (HR 1.79) and vascular calcifications (HR 1.29) as predictors for 3-year and vascular calcifications (HR 1.51) for 30-day mortality.<br /><b>Conclusion</b><br />Patients with ESRD and CKD constitute a vulnerable patient group with extensive vascular calcifications. Immediate procedural results were largely unaffected by renal impairment, yielding TAVI a particularly valuable treatment option in these high-risk operative patients. Mid-term survival was determined by underlying renal disease, cardiovascular comorbidities, and vascular calcifications as a novel risk marker.<br /><br />© 2021. The Author(s).<br /><br /><small>Clin Res Cardiol: 01 Dec 2022; 111:1313-1324</small></div>
Grundmann D, Linder M, Goßling A, Voigtländer L, ... Conradi L, Seiffert M
Clin Res Cardiol: 01 Dec 2022; 111:1313-1324 | PMID: 34773135
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<div><h4>Real-world comparative effectiveness of ARNI versus ACEi/ARB in HF with reduced or mildly reduced ejection fraction.</h4><i>Fu M, Pivodic A, Käck O, Costa-Scharplatz M, Dahlström U, Lund LH</i><br /><b>Aims</b><br />Sacubitril/valsartan is a first-in-class angiotensin receptor-neprilysin inhibitor (ARNI) with a class-1 guideline recommendation. We assessed the real-world effectiveness of ARNI versus angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARB) on all-cause and cardiovascular (CV)-related mortality and hospitalizations in heart failure (HF) with reduced or mildly reduced ejection fraction (EF).<br /><b>Methods</b><br />Patient-level clinical, laboratory, drug dispensation, hospitalization, and mortality data were derived from the Swedish Heart Failure Registry (SwedeHF) and interlinked databases (1 April 2016-31 December 2020). Eligible ARNI:ACEi/ARB patients (n = 7275:24,604) had a left ventricular EF < 50%. Mortality and hospitalizations with ARNI (≤ 3 months pre-/post-1 April 2016 index [SwedeHF]; n = 1506) versus ACEi/ARB (≤ 3 months post-index; n = 17,108) were assessed using propensity score matching (1:1 ratio) with clinical variables, and sensitivity analysis (1:2/1:3 with, and 1:2 without clinical variables).<br /><b>Results</b><br />ARNI induced a 23% reduction in all-cause mortality versus ACEi/ARB (1:1 hazard ratio [HR; 95% confidence interval (CI)]: 0.77 [0.63-0.95], p = 0.013), and a non-significant 23% relative risk reduction in CV-related mortality (0.77 [0.54-1.09], p = 0.13), but no difference in all-cause or CV-related hospitalization (1.02 [0.91-1.13]; p = 0.76; 1.01 [0.91-1.15]; p = 0.84, respectively). Sensitivity analyses confirmed all-cause mortality was reduced for ARNI versus ACEi/ARB (HR 0.90 [95% CI 0.82-0.99], p = 0.026), but not CV-related mortality (HR 1.04 [95% CI 0.89-1.22], p = 0.63).<br /><b>Conclusions</b><br />In this nationwide real-world study including a population of patients with HF with reduced or mildly reduced EF, ARNI as part of guideline-led Swedish clinical practice was associated with a statistically significant relative risk reduction in all-cause mortality compared with ACEi/ARB.<br /><br />© 2022. The Author(s).<br /><br /><small>Clin Res Cardiol: 29 Nov 2022; epub ahead of print</small></div>
Fu M, Pivodic A, Käck O, Costa-Scharplatz M, Dahlström U, Lund LH
Clin Res Cardiol: 29 Nov 2022; epub ahead of print | PMID: 36443599
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<div><h4>Autopsy-based histopathological characterization of myocarditis after anti-SARS-CoV-2-vaccination.</h4><i>Schwab C, Domke LM, Hartmann L, Stenzinger A, Longerich T, Schirmacher P</i><br /><AbstractText>Cases of myocarditis, diagnosed clinically by laboratory tests and imaging have been described in the context of mRNA-based anti-SARS-CoV-2 vaccination. Autopsy-based description of detailed histological features of vaccine-induced myocarditis is lacking. We describe the autopsy findings and common characteristics of myocarditis in untreated persons who received anti-SARS-CoV-2 vaccination. Standardized autopsies were performed on 25 persons who had died unexpectedly and within 20 days after anti-SARS-CoV-2 vaccination. In four patients who received a mRNA vaccination, we identified acute (epi-)myocarditis without detection of another significant disease or health constellation that may have caused an unexpected death. Histology showed patchy interstitial myocardial T-lymphocytic infiltration, predominantly of the CD4 positive subset, associated with mild myocyte damage. Overall, autopsy findings indicated death due to acute arrhythmogenic cardiac failure. Thus, myocarditis can be a potentially lethal complication following mRNA-based anti-SARS-CoV-2 vaccination. Our findings may aid in adequately diagnosing unclear cases after vaccination and in establishing a timely diagnosis in vivo, thus, providing the framework for adequate monitoring and early treatment of severe clinical cases.</AbstractText><br /><br />© 2022. The Author(s).<br /><br /><small>Clin Res Cardiol: 27 Nov 2022; epub ahead of print</small></div>
Schwab C, Domke LM, Hartmann L, Stenzinger A, Longerich T, Schirmacher P
Clin Res Cardiol: 27 Nov 2022; epub ahead of print | PMID: 36436002
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<div><h4>Outcome of patients with idiopathic ventricular fibrillation and correlation with ECG markers of early repolarization.</h4><i>Rath B, Willy K, Ellermann C, Leitz P, ... Frommeyer G, Eckardt L</i><br /><b>Background</b><br />Early repolarization pattern (ERP) has been associated with idiopathic ventricular fibrillation (IVF) and with cardiovascular mortality in the general population. As there is limited data about long- term outcome of IVF, the aim of our study was to observe ventricular arrhythmia (VA) recurrences in these patients and to identify a possible correlation of VA with ECG markers of early repolarization.<br /><b>Methods and results</b><br />We investigated 56 consecutive IVF patients who received an implantable cardioverter-defibrillator for secondary prevention. ERP was defined as a J-point elevation ≥ 0.1 mV in two or more contiguous inferior or lateral leads. Markers of early repolarization were present in 32.1% of cases with a preponderance of QRS slurring (77.8%). During a mean follow-up of 41.2 months, 11 patients (19.6%) received in total 18 adequate ICD-therapies. VF was most the common cause for ICDtherapy (61.1%) but monomorphic VT also occurred in four patients. Presence of ERP was associated with a significant trend towards arrhythmia recurrences. 38.9% patients with ERP received appropriate ICD-therapies whereas only 10.5% of patients without ERP had arrhythmia recurrence (p = 0.05). Inappropriate ICD-therapies occurred in seven patients (12.5%) with a non-significant trend towards a higher incidence in patients with a transvenous ICD (p = 0.15).<br /><b>Conclusion</b><br />A significant correlation between ERP and VA recurrences in patients with IVF could be observed. Though monomorphic VA also play a role in the studied IVF-population, our data support the use of the S-ICD in this collective.<br /><br />© 2022. The Author(s).<br /><br /><small>Clin Res Cardiol: 19 Nov 2022; epub ahead of print</small></div>
Rath B, Willy K, Ellermann C, Leitz P, ... Frommeyer G, Eckardt L
Clin Res Cardiol: 19 Nov 2022; epub ahead of print | PMID: 36401623
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<div><h4>Diuretic dose trajectories in dilated cardiomyopathy: prognostic implications.</h4><i>Nuzzi V, Cannatà A, Pellicori P, Manca P, ... Merlo M, Sinagra G</i><br /><b>Background</b><br />For patients with heart failure, prescription of loop diuretics (LD) and of higher doses are associated with an adverse prognosis. We investigated LD dose trajectories and their associations with outcomes in patients with dilated cardiomyopathy (DCM).<br /><b>Methods</b><br />Associations between outcomes and both furosemide-equivalent dose (FED) at enrolment and change in FED in the subsequent 24 months were evaluated. According to FED trajectory, patients were classified as (i) dose (FED increase by ≥ 50% or newly initiated); (ii) dose↓ (FED decrease by ≥ 50%); (iii) stable dose (change in FED by < 50%); and (iv) never-users. The primary outcome was all-cause-death/heart transplantation/ventricular-assist-device/heart failure hospitalization. The secondary outcome was all-cause-death/heart transplantation/ventricular-assist-device.<br /><b>Results</b><br />Of 1,131 patients enrolled, 738 (65%) were prescribed LD at baseline. Baseline FED was independently associated with outcome (HR per 20 mg increase: 1.12 [95% CI 1.04-1.22, p = 0.003]. Of the 908 with information on FED within 24 months from enrolment, 31% were never-users; 29% were dose↓; 26% were stable dose and 14% were dose↑. In adjusted models, compared to never-users, stable dose had a higher risk of the primary outcome (HR 2.42 [95% CI 1.19-4.93], p = 0.015), while dose↑ had the worst prognosis (HR 2.76 [95% CI 1.27-6.03], p = 0.011). Results were similar for the secondary outcome. Compared to patients who remained on LD, discontinuation of LD (143, 24%) was associated with an improved outcome (HR 0.43 [95% CI 0.28-0.65], p < 0.001).<br /><b>Conclusions</b><br />In patients with DCM, LD use and increasing FED are powerful markers of adverse outcomes. Patients who never receive LD have an excellent prognosis. Among 1131 DCM patients 65% received loop diuretics at enrolment (upper left side). The bar chart on the upper right side shows the categorization in never-users/ dose↓/stable dose/ dose↑ over 24 months of follow-up. At the bottom is reported on the left side of each panel (observation period) the trajectory of LD dose in the four groups (left panel) and in patients who have their LD suspended vs those who continue LD (right panel) in the first two years. On the right side of each panel is shown the incidence of primary outcomes during the subsequent follow-up in the subgroups (outcome assessment).<br /><br />© 2022. The Author(s).<br /><br /><small>Clin Res Cardiol: 17 Nov 2022; epub ahead of print</small></div>
Nuzzi V, Cannatà A, Pellicori P, Manca P, ... Merlo M, Sinagra G
Clin Res Cardiol: 17 Nov 2022; epub ahead of print | PMID: 36385396
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<div><h4>Clinical implications and risk factors for QRS prolongation over time in heart failure patients.</h4><i>Berger M, Kumowski N, Straw S, Verket M, ... Witte KK, Schütt K</i><br /><b>Background</b><br />QRS prolongation is an established prognostic marker in heart failure (HF). In contrast, the role of QRS width progression over time has been incompletely explored. The current study investigates the role of QRS width progression over time on clinical status and identifies underlying predictors.<br /><b>Methods</b><br />Datasets of ≥ 2 consecutive visits from 100 attendees to our HF clinic between April and August 2021 were analysed for changes in QRS complex duration.<br /><b>Results</b><br />In total 240 datasets were stratified into tertiles based on change in QRS duration (mm/month) (1st tertile: - 1.65 [1.50] \'regression\'; 2nd tertile 0.03 [0.19] \'stable\', 3rd tertile 3.57 [10.11] \'progression\'). The incidence of the combined endpoint HF hospitalisation and worsening of symptomatic heart failure was significantly higher in the group with QRS width progression (3rd tertile) compared with the stable group (2nd tertile; log-rank test: p = 0.013). These patients were characterised by higher plasma NT-pro-BNP levels (p = 0.008) and higher heart rate (p = 0.007). A spline-based prediction model identified patients at risk of QRS width progression when NT-pro-BNP and heartrate were > 837 pg/ml and > 83/bpm, respectively. These markers were independent of guideline-directed medical HF therapy. Patients beyond both thresholds had a 14-fold increased risk of QRS width progression compared to those with neither or either alone (HR: 14.2 [95% 6.9 - 53.6]; p < 0.0001, p for interaction = 0.016).<br /><b>Conclusions</b><br />This pilot study demonstrates that QRS width progression is associated with clinical deterioration of HF. NTproBNP plasma levels and heart rate indicate patients at risk QRS width progression, independently of HF therapy.<br /><br />© 2022. The Author(s).<br /><br /><small>Clin Res Cardiol: 15 Nov 2022; epub ahead of print</small></div>
Berger M, Kumowski N, Straw S, Verket M, ... Witte KK, Schütt K
Clin Res Cardiol: 15 Nov 2022; epub ahead of print | PMID: 36378295
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<div><h4>Clinical trajectories and outcomes of patients with heart failure with preserved ejection fraction with normal or indeterminate diastolic function.</h4><i>Oeun B, Hikoso S, Nakatani D, Mizuno H, ... Sakata Y, OCVC-Heart Failure Investigators</i><br /><b>Background</b><br />We recently reported that nearly half of patients with heart failure with preserved ejection fraction (HFpEF) did not show echocardiographic diastolic dysfunction (DD), but had normal diastolic function (ND) or indeterminate diastolic function (ID). However, the clinical course and outcomes of patients with HFpEF with ND or ID (ND/ID) remain unknown.<br /><b>Methods</b><br />From the PURSUIT-HFpEF registry, we extracted 289 patients with HFpEF with ND/ID at discharge who had echocardiographic data at 1-year follow-up. Patients were classified according to the status of progression from ND/ID to DD at 1 year. Primary endpoint was a composite of all-cause death or HF rehospitalization.<br /><b>Results</b><br />Median age was 81 years, and 138 (47.8%) patients were female. At 1 year, 107 (37%) patients had progressed to DD. The composite endpoint occurred in 90 (31.1%) patients. Compared to patients without progression to DD, those with progression had a significantly higher cumulative rate of the composite endpoint (P < 0.001) and HF rehospitalization (P < 0.001) after discharge and at the 1-year landmark (P = 0.030 and P = 0.001, respectively). Progression to DD was independently associated with the composite endpoint (hazard ratio (HR): 2.014, 95%CI 1.239-3.273, P = 0.005) and HF rehospitalization (HR: 2.362, 95%CI 1.402-3.978) after discharge. Age (odds ratio (OR): 1.043, 95%CI 1.004-1.083, P = 0.031), body mass index (BMI) (OR: 1.110, 95%CI 1.031-1.195, P = 0.006), and albumin (OR: 0.452, 95%CI 0.211-0.969, P = 0.041) were independently associated with progression from ND/ID to DD.<br /><b>Conclusions</b><br />More than one-third of HFpEF patients with ND/ID progressed to DD at 1 year and had poor outcomes. Age, BMI and albumin were independently associated with this progression.<br /><b>Umin-ctr id</b><br />UMIN000021831.<br /><br />© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.<br /><br /><small>Clin Res Cardiol: 10 Nov 2022; epub ahead of print</small></div>
Oeun B, Hikoso S, Nakatani D, Mizuno H, ... Sakata Y, OCVC-Heart Failure Investigators
Clin Res Cardiol: 10 Nov 2022; epub ahead of print | PMID: 36357804
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<div><h4>Screening strategies for atrial fibrillation in the elderly population: a systematic review and network meta-analysis.</h4><i>Whitfield R, Ascenção R, da Silva GL, Almeida AG, Pinto FJ, Caldeira D</i><br /><AbstractText>Opportunistic screening for atrial fibrillation (AF) is currently recommended for patients aged 65 years and older. However, this has recently been called into question by two studies that report that opportunistic screening is no more effective than usual care. Furthermore, there seems to be no consensus on which is the most effective screening strategy (opportunistic or systematic). Thus, we aimed to compare the different AF detection strategies with each other using the methodology of systematic review with network meta-analysis. An electronic database search of MEDLINE, CENTRAL, and EMBASE was performed. In addition, we also searched OpenGrey, experts\' knowledge and screened the reference list of included studies or other relevant publications. The search was performed on the 2nd of November of 2020 and updated on the 20th of September of 2021. We performed a random-effects pairwise meta-analysis and a random-effects network meta-analysis within a frequentist framework in an intention to screen analysis. We reported the results as relative risk (RR) with 95% confidence intervals (CI). We assessed the confidence in the evidence using the GRADE framework. Nine studies were included, enrolling 80,665 participants. Pooled effect sizes suggested that systematic screening was effective when compared with usual care (RR 2.11; 95% CI 1.48-3.02; high GRADE confidence) and when compared with opportunistic screening (RR 1.86; CI 1.23-2.82; high GRADE confidence) but no significant difference was found between opportunistic screening and usual care (RR 1.13; 95% CI 0.79-1.63; low GRADE confidence). Systematic screening was the most effective strategy for detecting atrial fibrillation in individuals aged 65 years or older. Opportunistic screening was no more effective than usual care, but the results were weakened by a low quality of evidence due to risk of bias of the included studies and imprecision in the results. PROSPERO registration number: CRD42020218672.</AbstractText><br /><br />© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.<br /><br /><small>Clin Res Cardiol: 07 Nov 2022; epub ahead of print</small></div>
Whitfield R, Ascenção R, da Silva GL, Almeida AG, Pinto FJ, Caldeira D
Clin Res Cardiol: 07 Nov 2022; epub ahead of print | PMID: 36342504
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<div><h4>Defining the gap in heart failure treatment in patients with cardiac implantable electronic devices.</h4><i>Salimian S, Moghaddam N, Deyell MW, Virani SA, ... Andrade JG, Hawkins NM</i><br /><b>Background</b><br />The use of guideline-directed medical therapy (GDMT) is poorly described in patients with heart failure and reduced ejection fraction (HFrEF) with cardiac resynchronization therapy (CRT) and/or implantable cardioverter defibrillators (ICDs).<br /><b>Objective</b><br />To define the eligibility, uptake, dose, contraindications, and barriers to uptake of contemporary medical therapy in this population.<br /><b>Methods</b><br />Retrospective analysis of consecutive adults with ICD and/or CRT attending two Canadian tertiary centre device clinics between 1 March and 31 May 2021.<br /><b>Results</b><br />From 1005 device clinic consultations, 227 (22.6%) patients with HFrEF and CRT and/or ICD were included. GDMT eligibility was high: beta-blockers (99.6%), mineralocorticoid receptor antagonists (MRA) (89.0%), angiotensin receptor-neprilysin inhibitors (ARNI) (84.6%), and sodium-glucose cotransporter-2 inhibitors (SGLT2I) (87.7%). Contraindications were rare: beta-blockers (0.4%), MRA (11.0%), ARNI (15.4%), and SGLT2I (12.3%). Uptake of GDMT was high for beta-blockers (97.4%) but low for other medications: MRA (63.0%), ARNI (46.7%), SGLT2I (22.9%). Except for SGLT2I (84.6%) and beta-blockers (57.9%), less than one-half of patients were prescribed target-doses of MRA (10.5%), and ARNI (47.7%). Of the visits, GDMT was already optimal in 16%, electrophysiologists acted in 33% (21% prescribed, 7% ordered investigations, 5% referred to heart function services), and in the remaining visits, optimization was either deferred to another cardiologist (20%) or no plan was mentioned (25%), besides other reasons (4%).<br /><b>Conclusion</b><br />Despite broad eligibility for GDMT in patients with HFrEF and ICD/CRT, significant gaps in prescription and titration exist. Our results highlight the need to embed quality assurance initiatives in cardiac device clinics to improve HFrEF care.<br /><br />© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.<br /><br /><small>Clin Res Cardiol: 03 Nov 2022; epub ahead of print</small></div>
Salimian S, Moghaddam N, Deyell MW, Virani SA, ... Andrade JG, Hawkins NM
Clin Res Cardiol: 03 Nov 2022; epub ahead of print | PMID: 36329250
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<div><h4>Network meta-analysis of sacubitril/valsartan for the treatment of essential hypertension.</h4><i>Zhang Y, Zhao X, Huang H, Li M</i><br /><b>Aim</b><br />Sacubitril/valsartan has been demonstrated to reduce blood pressure in hypertensive patients, but the best dose remains unclear. We performed this network meta-analysis to determine the comparative efficacy and safety of three available doses of sacubitril/valsartan (i.e., 100, 200, and 400 mg).<br /><b>Methods and results</b><br />We searched four databases for relevant studies published before January 2022. Mean systolic and diastolic blood pressures in the sitting position (msSBP and msDBP) and ambulatory condition (24-h maSBP and maDBP) and adverse events (AEs) were assessed. Nine randomized controlled trials (RCTs) involving 5474 patients were included. Sacubitril/valsartan 200 mg once daily was slightly better than 400 mg once daily in lowering 24-h maDBP (MD, 1.31 mmHg; 95% CI 0.61-2.01 mmHg), slightly better than 100 mg once daily in lowering 24-h maSBP (MD, - 3.70 mmHg; 95% CI  - 6.22 to - 1.18 mmHg) and 24-h maDBP (MD, - 2.98; 95% CI - 5.11 to - 0.85), and slightly better than Valsartan 160 mg once daily in lowering 24-h maSBP (MD, - 3.23 mmHg; 95% CI, - 5.25 to - 1.21). 400 mg once daily of sacubitril/valsartan was better than 200 mg once daily in lowering msDBP (MD, - 9.38 mmHg; 95% CI - 17.79 to - 0.97 mmHg). Interestingly, 400 mg once daily of sacubitril/valsartan had fewer trial-specified AEs than 200 mg once daily (OR, 0.74; 95%CI 0.55-0.99). There was no statistical difference for the remaining comparisons.<br /><b>Conclusions</b><br />In hypertensive patients, 200 mg once daily of sacubitril/valsartan may exert a greater reduction in ambulatory blood pressure than 100 mg once daily and 200 mg once daily may not be inferior to 400 mg once daily. Moreover, it is not clear that sacubitril/valsartan lowers blood pressure more than an angiotensin receptor blocker. Further trials are required to determine the incremental value of sacubitril/valsartan as an anti-hypertensive agent.<br /><br />© 2022. The Author(s).<br /><br /><small>Clin Res Cardiol: 03 Nov 2022; epub ahead of print</small></div>
Zhang Y, Zhao X, Huang H, Li M
Clin Res Cardiol: 03 Nov 2022; epub ahead of print | PMID: 36326841
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<div><h4>Depressive symptoms in patients after primary and secondary prophylactic ICD implantation.</h4><i>Ensslin C, Berg J, Hermes-Laufer J, Keller LS, ... von Känel R, Schmied C</i><br /><b>Objective</b><br />Implantable cardioverter defibrillators (ICD) are successfully used to treat life-threatening arrhythmias and prevent sudden cardiac death. However, they are also known to have a major psychological impact leading to higher prevalence of depression and anxiety in a substantial proportion of patients. The aim of this study was to assess the prevalence of depressive symptoms in a large cohort of ICD carriers with a different clinical background and to compare prevalence and risk factors between patients with primary and secondary prophylactic indication for ICD implantation.<br /><b>Methods</b><br />315 out of 622 patients (50.6%), who regularly attended ICD assessments at the University Hospital Zurich completed the Beck Depression Inventory (BDI I-II) to estimate current depressive symptoms.<br /><b>Results</b><br />Overall, depressive symptoms were common in ICD patients, with 20.3% of the patients showing clinically relevant depression (12.4% mild depressive symptoms, 6.0% moderate, 1.9% severe). Moderate to severe depressive symptoms seem to be more likely in patients with secondary prophylactic indication of the ICD as compared to a group of patients with primary prophylactic implantation. Patients that received more than 5 ICD shocks since implantation reveal more depressive symptoms than those with less events. Mean BDI Score in total (n = 315) was at 8.44 ± 7.56 without a statistically significant difference between the primary (M = 8.04 ± 7.10, n = 153) and secondary (M = 8.81 ± 7.98, n = 162) preventive group (p value = 0.362), even after adjustment for various clinical characteristics. ICD patients should therefore be well supported and advised concerning the psychological impact of their device and particular aspects of daily life concerns (e.g. physical activity), with a special focus on patients, who have received multiple shocks.<br /><br />© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.<br /><br /><small>Clin Res Cardiol: 01 Nov 2022; 111:1210-1218</small></div>
Ensslin C, Berg J, Hermes-Laufer J, Keller LS, ... von Känel R, Schmied C
Clin Res Cardiol: 01 Nov 2022; 111:1210-1218 | PMID: 34779916
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Abstract
<div><h4>Quantitative distance and electrocardiographic parameters for lead-implanted site selection to enhance the success likelihood of left bundle branch pacing.</h4><i>Lu W, Lin J, Chen K, Dai Y, ... Zhou Y, Zhang S</i><br /><b>Background</b><br />Left bundle branch pacing (LBBP) is a novel near-physiological pacing method that still lacks quantitative criteria to guide the selection of lead-implanted sites to enhance the success likelihood of lead deployments. This study aimed to quantitatively analyze the relationships of LBBP success likelihood to the distribution of lead-implanted sites and the lead-localization-pacing electrocardiographic (ECG) features.<br /><b>Methods</b><br />All the lead-implanted sites in patients with finally successful LBBP were enrolled for analysis, including successful and failed sites. A novel coordinate system was invented to describe the sites\' distribution as longitudinal distance (longit-dist) and lateral distance (lat-dist). Corrected distance parameters were generated to eliminate the cardiac dimension variations. The lead-localization-pacing ECG parameters were also collected, such as paced QRS duration (locat-QRSd), left ventricular activation time (locat-LVAT), LVAT/QRSd ratio (locat-LVAT/QRSd), and QRS directions.<br /><b>Results</b><br />A total of 94 patients with 105 successful sites and 93 failed sites were enrolled. Longit-dist and corrected longit-dist of successful sites were significantly longer, while locat-QRSd and locat-LVAT were shorter and locat-LVAT/QRSd was lower than failed sites. There was a positive dose-response relationship between LBBP success likelihood and corrected longit-dist with a cut-off of 26.95 mm, whereas there were negative dose-response relationships of LBBP success likelihood to locat-QRSd, locat-LVAT, and locat-LVAT/QRSd with the cut-offs of 142 ms, 92 ms, and 64.7%, respectively. Downward QRS direction in II/III ECG leads was also associated with successful LBBP.<br /><b>Conclusion</b><br />Longit-dist, locat-QRSd, locat-LVAT, and locat-LVAT/QRSd were quantitative parameters to guide the selection of lead-implanted sites during LBBP implantation. Quantitative distance and electrocardiographic parameters for lead-implanted site selection to enhance the success likelihood of left bundle branch pacing. LBBP, left bundle branch pacing; Longit-dist, longitudinal distance; CL-apex-dist, distance from contraction line to apex; LBBB, left bundle branch block; IVCD, intraventricular conduction delay; Locat-QRSd, lead-localization-pacing QRS duration; Locat-LVAT, lead-localization-pacing left ventricular activation time; Locat-LVAT/QRSd, lead-localization-pacing LVAT/QRSd ratio.<br /><br />© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.<br /><br /><small>Clin Res Cardiol: 01 Nov 2022; 111:1219-1230</small></div>
Lu W, Lin J, Chen K, Dai Y, ... Zhou Y, Zhang S
Clin Res Cardiol: 01 Nov 2022; 111:1219-1230 | PMID: 34761309
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Abstract
<div><h4>Long-term follow-up of patients undergoing renal sympathetic denervation.</h4><i>Zeijen VJM, Feyz L, Nannan Panday R, Veen K, ... Van Mieghem NM, Daemen J</i><br /><b>Objectives</b><br />Renal denervation (RDN) proved to significantly lower blood pressure (BP) at 2-6 months in patients on and off antihypertensive drugs. Given a lack of longer-term follow-up data, our aim was to assess the safety and efficacy of RDN up to five years taking into account antihypertensive drug regimen changes over time.<br /><b>Methods</b><br />In the present single-center study, patients underwent RDN for (therapy resistant) hypertension. Patients underwent protocolized yearly follow-up out to five years. Data were collected on 24-h ambulatory BP and office BP monitoring, renal function, antihypertensive drug regimen, and safety events, including non-invasive renal artery imaging at 6/12 months. Efficacy analyses were performed using linear mixed-effects models.<br /><b>Results</b><br />Seventy-two patients with mean age 63.3 ± 9.5 (SD) years (51% female) were included. Median follow-up time was 3.5 years and Clark\'s Completeness Index was 72%. Baseline ambulatory daytime BP was 146.1/83.7 ± 17.4/12.2 mmHg under a mean number of 4.9 ± 2.7 defined daily doses (DDD). At five years, ambulatory daytime systolic BP as calculated from the mixed model was 120.8 (95% CI 114.2-127.5) mmHg and diastolic BP was 73.3 (95% CI 69.4-77.3) mmHg, implying a reduction of -20.9/-8.3 mmHg as compared to baseline estimates (p < 0.0001). The number of DDDs remained stable over time (p = 0.87). No procedure-related major adverse events resulting in long-term consequences were observed.<br /><b>Conclusions</b><br />The BP-lowering effect of RDN was safely maintained at least five years post-procedure as reflected by a significant decrease in ambulatory daytime BP in the absence of escalating antihypertensive drug therapy over time.<br /><br />© 2022. The Author(s).<br /><br /><small>Clin Res Cardiol: 01 Nov 2022; 111:1256-1268</small></div>
Zeijen VJM, Feyz L, Nannan Panday R, Veen K, ... Van Mieghem NM, Daemen J
Clin Res Cardiol: 01 Nov 2022; 111:1256-1268 | PMID: 35851428
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<div><h4>Cost-effectiveness of noninvasive telemedical interventional management in patients with heart failure: health economic analysis of the TIM-HF2 trial.</h4><i>Sydow H, Prescher S, Koehler F, Koehler K, ... Willich SN, Reinhold T</i><br /><b>Background</b><br />Noninvasive remote patient management (RPM) in patients with heart failure (HF) has been shown to reduce the days lost due to unplanned cardiovascular hospital admissions and all-cause mortality in the Telemedical Interventional Management in Heart Failure II trial (TIM-HF2). The health economic implications of these findings are the focus of the present analyses from the payer perspective.<br /><b>Methods and results</b><br />A total of 1538 participants of the TIM-HF2 randomized controlled trial were assigned to the RPM and Usual Care group. Health claims data were available for 1450 patients (n = 715 RPM group, n = 735 Usual Care group), which represents 94.3% of the original TIM-HF2 patient population, were linked to primary data from the study documentation and evaluated in terms of the health care cost, total cost (accounting for intervention costs), costs per day alive and out of hospital (DAOH), and cost per quality-adjusted life year (QALY). The average health care costs per patient year amounted to € 14,412 (95% CI 13,284-15,539) in the RPM group and € 17,537 (95% CI 16,179-18,894) in the UC group. RPM led to cost savings of € 3125 per patient year (p = 0.001). After including the intervention costs, a cost saving of € 1758 per patient year remained (p = 0.048).<br /><b>Conclusion</b><br />The additional noninvasive telemedical interventional management in patients with HF was cost-effective compared to standard care alone, since such intervention was associated with overall cost savings and superior clinical effectiveness.<br /><br />© 2021. The Author(s).<br /><br /><small>Clin Res Cardiol: 01 Nov 2022; 111:1231-1244</small></div>
Sydow H, Prescher S, Koehler F, Koehler K, ... Willich SN, Reinhold T
Clin Res Cardiol: 01 Nov 2022; 111:1231-1244 | PMID: 34894273
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<div><h4>Clinical and echocardiographic risk factors for device-related thrombus after left atrial appendage closure: an analysis from the multicenter EUROC-DRT registry.</h4><i>Vij V, Piayda K, Nelles D, Gloekler S, ... Nickenig G, Sedaghat A</i><br /><b>Background</b><br />Data on Device-related Thrombus (DRT) after left atrial appendage closure (LAAC) remain scarce. This study aimed to investigate risk factors for DRT from centers reporting to the EUROC-DRT registry.<br /><b>Methods</b><br />We included 537 patients (112 with DRT and 425 without DRT) who had undergone LAAC between 12/2008 and 04/2019. Baseline and implantation characteristics, anti-thrombotic treatment and clinical outcomes were compared between both groups in uni- and multivariate analyses. Additional propensity-score matching (PSM) was conducted to focus on the role of implantation characteristics.<br /><b>Results</b><br />Patients with DRT showed higher rates of previous stroke/transient ischemic attack (TIA) (49.1% vs. 34.7%, p < 0.01), spontaneous echocardiographic contrast (SEC) (44.9% vs. 27.7%, p < 0.01) and lower left atrial appendage (LAA) peak emptying velocity (35.4 ± 18.5 vs. 42.4 ± 18.0 cm/s, p = 0.02). Occluders implanted in DRT patients were larger (25.5 ± 3.8 vs. 24.6 ± 3.5 mm, p = 0.03) and implanted deeper in the LAA (mean depth: 7.6 ± 4.7 vs. 5.7 ± 4.7 mm, p < 0.01). Coverage of the appendage ostium was achieved less often in DRT patients (69.5% vs. 81.5%, p < 0.01), while DRT patients were less frequently on oral anticoagulation (7.1% vs. 16.7%, p < 0.01). Multivariate analysis identified age, prior stroke/TIA and SEC as independent risk factors for DRT. After PSM, implantation depth was found to be predictive. Rates of stroke/TIA were higher in DRT patients (13.5% vs. 3.8%, Hazard Ratio: 4.21 [95%-confidence interval: 1.88-9.49], p < 0.01).<br /><b>Conclusions</b><br />DRT after LAAC is associated with adverse outcome and appears to be of multifactorial origin, depending on patient characteristics, anticoagulation regimen and device position.<br /><br />© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.<br /><br /><small>Clin Res Cardiol: 01 Nov 2022; 111:1276-1285</small></div>
Vij V, Piayda K, Nelles D, Gloekler S, ... Nickenig G, Sedaghat A
Clin Res Cardiol: 01 Nov 2022; 111:1276-1285 | PMID: 35849156
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<div><h4>Outcomes of conduction system pacing compared to right ventricular pacing as a primary strategy for treating bradyarrhythmia: systematic review and meta-analysis.</h4><i>Abdin A, Aktaa S, Vukadinović D, Arbelo E, ... Vernooy K, Gale CP</i><br /><b>Background</b><br />Right ventricular pacing (RVP) may cause electrical and mechanical desynchrony leading to impaired left ventricular ejection fraction (LVEF). We investigated the outcomes of RVP with His bundle pacing (HBP) and left bundle branch pacing (LBBP) for patients requiring a de novo permanent pacemaker (PPM) for bradyarrhythmia.<br /><b>Methods and results</b><br />Systematic review of randomized clinical trials and observational studies comparing HBP or LBP with RVP for de novo PPM implantation between 01 January 2013 and 17 November 2020 was performed. Random and fixed effects meta-analyses of the effect of pacing technology on outcomes were performed. Study outcomes included all-cause mortality, heart failure hospitalization (HFH), LVEF, QRS duration, lead revision, atrial fibrillation, procedure parameters, and pacing metrics. Overall, 9 studies were included (6 observational, 3 randomised). HBP compared with RVP was associated with decreased HFH (risk ratio [RR] 0.68, 95% confidence interval [CI] 0.49-0.94), preservation of LVEF (mean difference [MD] 0.81, 95% CI - 1.23 to 2.85 vs. - 5.72, 95% CI - 7.64 to -3.79), increased procedure duration (MD 15.17 min, 95% CI 11.30-19.04), and increased lead revisions (RR 5.83, 95% CI 2.17-15.70, p = 0.0005). LBBP compared with RVP was associated with shorter paced QRS durations (MD 5.6 ms, 95% CI - 6.4 to 17.6) vs. (51.0 ms, 95% CI 39.2-62.9) and increased procedure duration (MD 37.78 min, 95% CI 20.04-55.51).<br /><b>Conclusion</b><br />Of the limited studies published, this meta-analysis found that HBP and LBBP were superior to RVP in maintaining physiological ventricular activation as an initial pacing strategy.<br /><br />© 2021. The Author(s).<br /><br /><small>Clin Res Cardiol: 01 Nov 2022; 111:1198-1209</small></div>
Abdin A, Aktaa S, Vukadinović D, Arbelo E, ... Vernooy K, Gale CP
Clin Res Cardiol: 01 Nov 2022; 111:1198-1209 | PMID: 34410461
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This program is still in alpha version.