<div><h4>Effect of sacubitril/valsartan on cardiac remodeling compared with other renin-angiotensin system inhibitors: a difference-in-difference analysis of propensity-score matched samples.</h4><i>Carluccio E, Dini FL, Correale M, Dattilo G, ... Palazzuoli A, Working Group on Heart Failure of the Italian Society of Cardiology</i><br /><b>Background</b><br />In patients with heart failure with reduced ejection fraction (HFrEF), treatment with sacubitril-valsartan (S/V) may reverse left ventricular remodeling (rLVR). Whether this effect is superior to that induced by other renin-angiotensin system (RAS) inhibitors is not well known.<br /><b>Methods</b><br />HFrEF patients treated with S/V (n = 795) were compared, by propensity score matching, with a historical cohort of 831 HFrEF patients (non-S/V group) treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (RAS inhibitors). All patients were also treated with beta-blockers and shared the same protocol with repeat echocardiogram 8-12 months after starting therapy. The difference-in-difference (DiD) analysis was used to evaluate the impact of S/V on CR indices between the two groups.<br /><b>Results</b><br />After propensity score matching, compared to non-S/V group (n = 354), S/V group (n = 354) showed a relative greater reduction in end-diastolic and end-systolic volume index (ESVI), and greater increase in ejection fraction (DiD estimator =  + 5.42 mL/m<sup>2</sup>, P = 0.0005; + 4.68 mL/m<sup>2</sup>, P = 0.0009, and + 1.76%, P = 0.002, respectively). Reverse LVR (reduction in ESVI ≥ 15% from baseline) was more prevalent in S/V than in non-S/V group (34% vs 26%, P = 0.017), while adverse LVR (aLVR, increase in ESVI at follow-up ≥ 15%) was more frequent in non-S/V than in S/V (16% vs 7%, P < 0.001). The beneficial effect of S/V on CR over other RAS inhibitors was appreciable across a wide range of patient\'s age and baseline end-diastolic volume index, but it tended to attenuate in more dilated left ventricles (P for interaction = NS for both).<br /><b>Conclusion</b><br />In HFrEF patients treated with beta-blockers, sacubitril/valsartan is associated with a relative greater benefit in LV reverse remodeling indices than other RAS inhibitors.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 21 Sep 2023; epub ahead of print</small></div>

<div><h4>Disease severity, arrhythmogenesis, and fibrosis are related to longer action potentials in tetralogy of Fallot.</h4><i>Fürniss HE, Wülfers EM, Iaconianni P, Ravens U, ... Rog-Zielinska EA, Peyronnet R</i><br /><b>Background</b><br />Arrhythmias may originate from surgically unaffected right ventricular (RV) regions in patients with tetralogy of Fallot (TOF). We aimed to investigate action potential (AP) remodelling and arrhythmia susceptibility in RV myocardium of patients with repaired and with unrepaired TOF, identify possible correlations with clinical phenotype and myocardial fibrosis, and compare findings with data from patients with atrial septal defect (ASD), a less severe congenital heart disease.<br /><b>Methods</b><br />Intracellular AP were recorded ex vivo in RV outflow tract samples from 22 TOF and three ASD patients. Arrhythmias were provoked by superfusion with solutions containing reduced potassium and barium chloride, or isoprenaline. Myocardial fibrosis was quantified histologically and associations between clinical phenotype, AP shape, tissue arrhythmia propensity, and fibrosis were examined.<br /><b>Results</b><br />Electrophysiological abnormalities (arrhythmias, AP duration [APD] alternans, impaired APD shortening at increased stimulation frequencies) were generally present in TOF tissue, even from infants, but rare or absent in ASD samples. More severely diseased and acyanotic patients, pronounced tissue susceptibility to arrhythmogenesis, and greater fibrosis extent were associated with longer APD. In contrast, APD was shorter in tissue from patients with pre-operative cyanosis. Increased fibrosis and repaired-TOF status were linked to tissue arrhythmia inducibility.<br /><b>Conclusions</b><br />Functional and structural tissue remodelling may explain arrhythmic activity in TOF patients, even at a very young age. Surprisingly, clinical acyanosis appears to be associated with more severe arrhythmogenic remodelling. Further research into the clinical drivers of structural and electrical myocardial alterations, and the relation between them, is needed to identify predictive factors for patients at risk. Central illustration: summary diagram of essential study results. Note that not all results are depicted here. For more detail, see text. APA action potential amplitude, APD action potential duration, AUC area under the curve, TOF tetralogy of Fallot.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 19 Sep 2023; epub ahead of print</small></div>

<div><h4>Cardiovascular effects of relaxin-2: therapeutic potential and future perspectives.</h4><i>Almeida-Pinto N, Dschietzig TB, Brás-Silva C, Adão R</i><br /><AbstractText>The hormone relaxin-2 has emerged as a promising player in regulating the physiology of the cardiovascular system. Through binding to the relaxin family peptide receptor 1 (RXFP1), this hormone elicits multiple physiological responses including vasodilation induction, reduction of inflammation and oxidative stress, and angiogenesis stimulation. The role of relaxin-2, or its recombinant human form known as serelaxin, has been investigated in preclinical and clinical studies as a potential therapy for cardiovascular diseases, especially heart failure, whose current therapy is still unoptimized. However, evidence from past clinical trials has been inconsistent and further research is needed to fully understand the potential applications of relaxin-2. This review provides an overview of serelaxin use in clinical trials and discusses future directions in the development of relaxin-2 mimetics, which may offer new therapeutic options for patients with heart failure.</AbstractText><br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 18 Sep 2023; epub ahead of print</small></div>

<div><h4>Treatment of patients with multiple organ dysfunction syndrome (MODS) with an electromagnetic field coupled to biorhythmically defined impulse configuration: the MicrocircMODS study.</h4><i>Werdan K, Nuding S, Kühnert D, Kolthoum R, ... Wienke A, Sedding D</i><br /><b>Background</b><br />To potentially improve impaired vasomotion of patients with multiple organ dysfunction syndrome (MODS), we tested whether an electromagnetic field of low flux density coupled with a biorhythmically defined impulse configuration (Physical Vascular Therapy BEMER<sup>®</sup>, PVT), in addition to standard care, is safe and feasible and might improve disturbed microcirculatory blood flow and thereby improve global haemodynamics.<br /><b>Methods</b><br />In a prospective, monocentric, one-arm pilot study, 10 MODS patients (APACHE II score 20-35) were included. Patients were treated, in addition to standard care, for 4 days with PVT (3 treatment periods of 8 min each day; day 1: field intensity 10.5 μT; day 2:14 μT, day 3:17.5 μT; day 4:21.0 μT). Primary endpoint was the effect of PVT on sublingual microcirculatory perfusion, documented by microvascular flow index (MFI). Patient safety, adverse events, and outcomes were documented.<br /><b>Results</b><br />An increase in MFI by approximately 25% paralleled 4-day PVT, with the increase starting immediately after the first PVT and lasting over the total 4-day treatment period. Concerning global haemodynamics (secondary endpoints), halving vasopressor use within 24 h, and haemodynamic stabilisation paralleled 4-day PVT with an increase in cardiac index, stroke volume index, and cardiac power index by 30%-50%. No adverse events (AEs) or serious adverse events (SAEs) were classified as causally related to the medical product (PVT) or study. Three patients died within 28 days and one patient between 28 and 180 days.<br /><b>Conclusion</b><br />PVT treatment was feasible and safe and could be performed without obstruction of standard patient care. An increase in microcirculatory blood flow, a rapid reduction in vasopressor use, and an improvement in global haemodynamics paralleled PVT treatment. Findings of this pilot study allowed forming a concept for a randomized trial for further proof.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 17 Sep 2023; epub ahead of print</small></div>

<div><h4>Prognostic implications of baseline rhythm during catheter ablation for atrial tachycardia.</h4><i>Kahle AK, Alken FA, Scherschel K, Meyer C</i><br /><b>Background</b><br />Atrial tachycardias (AT) occurring in patients after previous atrial fibrillation (AF) ablation are increasingly observed in clinical practice. Catheter ablation is the treatment of choice but an optimal workflow to improve patient outcome has not been defined. The purpose of this study was to assess procedural and clinical outcome depending on baseline rhythm at the beginning of AT ablation.<br /><b>Methods</b><br />A total of 380 patients (69 (61-75) years, 56.6% male) who underwent catheter ablation for consecutive AT after previous AF ablation were studied.<br /><b>Results</b><br />At the beginning of the procedure, 140 patients (36.8%) presented in sinus rhythm (SR), 208 (54.7%) with AT and 32 (8.4%) with AF. Patients in SR or with AT underwent shorter procedures (173 (132-213) minutes vs. 161 (120-203) minutes vs. 226 (154-249) minutes; p = 0.002) with more frequent termination to SR (87.9% vs. 81.3% vs. 56.3%; p < 0.001) than patients with AF. Acute procedural success did not differ between patients in SR or with AT but was higher compared to those with AF (96.4% vs. 97.1% vs. 87.5%; p = 0.033). During a follow-up of 290 (181-680) days, patients in baseline SR experienced arrhythmia recurrences less often (36.4% vs. 49.5% vs. 68.8%; p = 0.002) than patients with AT or AF.<br /><b>Conclusion</b><br />Baseline rhythm during AT ablation predicts procedural and clinical outcome. Whereas acute procedural success does not differ between patients in SR or with AT, patients presenting in SR have a more favorable mid-term success rate.<br /><br />© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.<br /><br /><small>Clin Res Cardiol: 15 Sep 2023; epub ahead of print</small></div>

<div><h4>Physical exercise as a treatment for persisting symptoms post-COVID infection: review of ongoing studies and prospective randomized controlled training study.</h4><i>Kogel A, Machatschek M, Scharschmidt R, Wollny C, ... Laufs U, Fikenzer S</i><br /><b>Background:</b><br/>and purpose</b><br />No evidence-based treatment is available for patients with persisting symptoms post-COVID-19 infection. We hypothesized that physical exercise may represent a safe and effective treatment option for post-COVID.<br /><b>Methods</b><br />We performed a systematic search of the literature that revealed a lack of randomized training studies in patients post-COVID. Based on these findings, a prospective randomized controlled study with open-label and blinded endpoint evaluation was designed. 272 patients with symptoms of fatigue persisting over 6 weeks post-COVID infection were screened. Patients with pathological cardiovascular findings were excluded. 57 patients consented and were randomized to 4 weeks of supervised personalized strength and endurance training or usual care. The follow-up period was 3 and 6 months.<br /><b>Results</b><br />There were no adverse events related to the training. Spiroergometry of the training group showed a significantly higher increase in VO2peak (10.0 ± 12.7% vs. 0.1 ± 8.9%, p < 0.01, respectively) and oxygen pulse (9.8 ± 10.8% vs. 0.0 ± 13.9%, p < 0.05, respectively). Parameters of the Multidimensional Fatigue Inventory-20, McGill Quality of Life Questionnaire, and Post-COVID-19 Functional Status were improved after 4 weeks in both groups. In the follow-up period, the total physical activity per week was significantly greater in the exercise group than in controls (1280 ± 1192 min vs. 644 ± 554 min, p < 0.05, respectively). The improvements in fatigue and quality of life were not statistically different between the training and usual care groups.<br /><b>Conclusion</b><br />Exercise is safe and improves maximal exercise capacity in post-COVID patients. Fatigue and quality of life improve over time in individuals that are willing to participate in a training study irrespective of their allocation.<br /><b>Registration</b><br />German Clinical Trials Register: DRKS00026686. Date of registration: 27.09.2021.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 12 Sep 2023; epub ahead of print</small></div>

<div><h4>Catheter based left atrial appendage closure in-hospital outcomes in Germany from 2016 to 2020.</h4><i>Maier A, Kaier K, Heidt T, Westermann D, von Zur Mühlen C, Grundmann S</i><br /><b>Background</b><br />New and refined catheter based left atrial appendage (LAA) closure devices have been introduced in the past decade. The procedure can be performed using either an endocardial occlusion device or an epicardial loop stitch. We aimed to analyzed recent procedural safety.<br /><b>Methods</b><br />Catheter based LAA closures were identified in a complete nationwide German dataset via ICD and OPS codes from 2016 to 2020.<br /><b>Results</b><br />From 2016 to 2020, 28,039 endocardial and 213 epicardial occlusions were performed. Numbers of endocardial procedures increased from 5259 in 2016 to 5917 in 2020 (p = 0.020) in 387 centers with shifting of patients\' characteristics towards older age (β = 0.29, p < 0.001), more heart failure (β = 1.01, p < 0.001) and renal disease (β = 0.67, p = 0.001) and without a significant trend for in-hospital safety except more bleeding (β = 0.12, p = 0.05). In-hospital major adverse cardiac and cerebrovascular events (MACCE) or pericardial puncture were independent on center procedure numbers. The loop stitch procedure was performed in 15 centers. Patients were younger (76.17 ± 8.16 vs. 73.16 ± 8.99, p < 0.001) and had a lower comorbidity index (2.29 ± 1.93 vs. 1.92 ± 1.64, p = 0.005). Adjusted risk difference for pericardial effusion (8.04%; 95% CI 3.01-13.08%; p = 0.002) and pericardial puncture (6.60%; 95% CI 3.85-9.35%; p < 0.001) was higher for the loop stitch procedure, while risk of bleeding (- 1.85%; 95% CI - 3.01 to - 0.69%; p = 0.002), intracerebral bleeding (- 0.37%; 95% CI - 0.59 to - 0.15%; p = 0.001) and shock (- 1.41%; 95% CI - 2.44 to - 0.39%; p = 0.007) was lower. No significant difference was observed for in-hospital MACCE.<br /><b>Conclusions</b><br />Endocardial occlusion was the major catheter based LAA closure procedure in Germany without improvements in in-hospital safety from 2016 to 2020. In-hospital MACCE was independent on endocardial LAAC center volumes. <br /><b>Conclusions:</b><br/>on the comparison between the two procedure types must be made cautious as the LAA loop stitch occlusion was utilized limited in a minor number of centers. Catheter based left atrial appendage closure in-hospital outcomes in Germany from 2016 to 2020.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 12 Sep 2023; epub ahead of print</small></div>

<div><h4>Acute exposure to simulated nocturnal traffic noise and cardiovascular complications and sleep disturbance-results from a pooled analysis of human field studies.</h4><i>Hahad O, Schmidt FP, Hübner J, Foos P, ... Herzog J, Münzel T</i><br /><b>Objectives</b><br />A series of human field studies demonstrated that acute exposure to simulated nocturnal traffic noise is associated with cardiovascular complications and sleep disturbance, including endothelial dysfunction, increased blood pressure, and impaired sleep quality. A pooled analysis of these results remains to be established and is of tremendous interest to consolidate scientific knowledge.<br /><b>Methods</b><br />We analyzed data from four randomized crossover studies (published between 2013 to 2021 and conducted at the University Medical Center Mainz, Germany). A total of 275 subjects (40.4% women, mean age 43.03 years) were each exposed to one control scenario (regular background noise) and at least to one traffic noise scenario (60 aircraft or train noise events) in their homes during nighttime. After each night, the subjects visited the study center for comprehensive cardiovascular function assessment, including the measurement of endothelial function and hemodynamic and biochemical parameters, as well as sleep-related variables.<br /><b>Results</b><br />The pooled analysis revealed a significantly impaired endothelial function when comparing the two different noise sequences (0-60 vs. 60-0 simulated noise events, mean difference in flow-mediated dilation -2.00%, 95% CI -2.32; -1.68, p < 0.0001). In concordance, mean arterial pressure was significantly increased after traffic noise exposure (mean difference 2.50 mmHg, 95% CI 0.54; 4.45, p = 0.013). Self-reported sleep quality, the restfulness of sleep, and feeling in the morning were significantly impaired after traffic noise exposure (all p < 0.0001).<br /><b>Discussion</b><br />Acute exposure to simulated nocturnal traffic noise is associated with endothelial dysfunction, increased mean arterial pressure, and sleep disturbance.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 11 Sep 2023; epub ahead of print</small></div>

<div><h4>Temporal trends of case-fatality in patients undergoing dual-injection coronary chronic total occlusion recanalization.</h4><i>Blessing R, Keller K, Dimitriadis Z, Münzel T, Gori T, Hobohm L</i><br /><b>Aims</b><br />Recently, interventional techniques and material to treat chronic total occlusion (CTO) with percutaneous coronary intervention (PCI) have evolved significantly. Nevertheless, it is still unknown whether this progress improved treatment success and patients\' outcome. In a nationwide sample, we sought to analyze trends of patients\' characteristics, complications and in-hospital case-fatality of patients undergoing CTO revascularization in Germany.<br /><b>Methods and results</b><br />We analyzed data on characteristics, treatments, and in-hospital outcomes for all coronary artery disease (CAD) patients (ICD-code I25) undergoing dual-injection CTO recanalization (OPS procedural code: 8-839.9) in Germany from 2009 to 2020. Overall, 4,998,457 inpatients aged ≥ 18 years with diagnosis of CAD were treated in German hospitals in this period. Among these, 52,879 patients (1.1%) underwent CTO recanalization. Annual number of CTO PCIs increased from 1263 in 2009 to 6435 in 2020 (β 3.48 [95% CI 3.44-3.52]; p < 0.001) in parallel with a significant decrease of case-fatality (2.2% in 2009 to 1.4% in 2020; β  - 0.60 [95% CI  - 0.82 to  - 0.39]; p < 0.001). Overall, 754 (1.4%) patients with CTO recanalization died during the in-hospital stay and in-hospital case-fatality grew exponentially with age (β 0.82 [95% CI 0.73-0.90]; p < 0.001). Significant predictors of in-hospital case fatality with an OR > 3 were cancer, stroke, hemopericardium, acute renal failure, pulmonary embolism and shock.<br /><b>Conclusion</b><br />Annual number of CTO procedures performed in Germany increased from 2009 to 2020 with a concomitant anti-proportional decrease in the case-fatality. Our findings may help to draw more attention to predictors of in-hospital case fatality in patients hospitalized for CTO recanalization.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 11 Sep 2023; epub ahead of print</small></div>

<div><h4>OECD indicator \'AMI 30-day mortality\' is neither comparable between countries nor suitable as indicator for quality of acute care.</h4><i>Stolpe S, Kowall B, Werdan K, Zeymer U, ... Schneider S, Stang A</i><br /><b>Background</b><br />Hospital mortality after acute myocardial infarction (AMI, ICD-10: I21-I22) is used as OECD indicator of the quality of acute care. The reported AMI hospital mortality in Germany is more than twice as high as in the Netherlands or Scandinavia. Yet, in Europe, Germany ranks high in health spending and availability of cardiac procedures. We provide insights into this contradictory situation.<br /><b>Methods</b><br />Information was collected on possible factors causing the reported differences in AMI mortality such as prevalence of risk factors or comorbidities, guideline conform treatment, patient registration, and health system structures of European countries. International experts were interviewed. Data on OECD indicators \'AMI 30-day mortality using unlinked data\' and \'average length of stay after AMI\' were used to describe the association between these variables graphically and by linear regression.<br /><b>Results</b><br />Differences in prevalence of risk factors or comorbidities or in guideline conform acute care account only to a smaller extent for the reported differences in AMI hospital mortality. It is influenced mainly by patient registration rules and organization of health care. Non-reporting of day cases as patients and centralization of AMI care-with more frequent inter-hospital patient transfers-artificially lead to lower calculated hospital mortality. Frequency of patient transfers and national reimbursement policies affect the average length of stay in hospital which is strongly associated with AMI hospital mortality (adj R<sup>2</sup> = 0.56). AMI mortality reported from registries is distorted by different underlying populations.<br /><b>Conclusion</b><br />Most of the variation in AMI hospital mortality is explained by differences in patient registration and organization of care instead of differences in quality of care, which hinders cross-country comparisons of AMI mortality. Europe-wide sentinel regions with comparable registries are necessary to compare (acute) care after myocardial infarction.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 08 Sep 2023; epub ahead of print</small></div>

<div><h4>Diagnosing post-capillary hypertension in patients with left heart disease: impact of new guidelines.</h4><i>Güder G, Reiter T, Fette G, Hundertmark M, ... Störk S, Held M</i><br /><b>Background</b><br />In 2022, the definition of pulmonary hypertension (PH) in the presence of left heart disease was updated according to the new joint guidelines of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS). The impact of the new ESC/ERS definition on the prevalence of post-capillary PH (pc-PH) and its subgroups of isolated post-capillary (Ipc-PH) and combined pre- and post-capillary PH (Cpc-PH) in patients with left heart disease is unclear.<br /><b>Methods</b><br />We retrospectively identified N = 242 patients with left heart disease with available data on right heart catheterisation (RHC) and cardiac magnetic resonance imaging (CMR). The proportion of pc-PH and its subgroups was calculated according to the old and new ESC/ERS PH definition. As the old definition did not allow the exact allocation of all patients with pc-PH into a respective subgroup, unclassifiable patients (Upc-PH) were regarded separately.<br /><b>Results</b><br />Seventy-six out of 242 patients had pc-PH according to the new ESC/ERS definitions, with 72 of these patients also meeting the criteria of the old definition. Using the old definition, 50 patients were diagnosed with Ipc-PH, 4 with Cpc-PH, and 18 with Upc-PH. Applying the new definition, Ipc-PH was diagnosed in 35 patients (4 newly), and Cpc-PH in 41 patients. No CMR parameter allowed differentiating between Ipc-PH and Cpc-PH, regardless of which guideline version was used.<br /><b>Conclusion</b><br />Applying the new ESC/ERS 2022 guideline definitions mildly increased the proportion of patients diagnosed with pc-PH (+ 5.5%) but markedly increased Cpc-PH diagnoses. This effect was driven by the allocation of patients with formerly unclassifiable forms of post-capillary PH to the Cpc-PH subgroup and a significant shift of patients from the Ipc-PH to the Cpc-PH subgroup. Distribution of post-capillary pulmonary hypertension (pc-PH) subgroups according to the European Society of Cardiology/European Respiratory Society (ESC/ERS) PH guidelines from 2015 and 2022 in N = 242 patients with left heart disease.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 05 Sep 2023; epub ahead of print</small></div>

<div><h4>The treatment of chronic anemia in heart failure: a global approach.</h4><i>Bianchi VE, von Haehling S</i><br /><AbstractText>Chronic anemia is an independent risk factor for mortality in patients with heart failure (HF). Restoring physiological hemoglobin (Hb) levels is essential to increase oxygen transport capacity to tissues and improve cell metabolism as well as physical and cardiac performance. Nutritional deficits and iron deficiency are the major causes of chronic anemia, but other etiologies include chronic kidney disease, inflammatory processes, and unexplained anemia. Hormonal therapy, including erythropoietin (EPO) and anabolic treatment in chronic anemia HF patients, may contribute to improving Hb levels and clinical outcomes. Although preliminary studies showed a beneficial effect of EPO therapy on cardiac efficiency and in HF, more recent studies have not confirmed this positive impact of EPO, alluding to its side effect profile. Physical exercise significantly increases Hb levels and the response of anemia to treatment. In malnourished patients and chronic inflammatory processes, low levels of anabolic hormones, such as testosterone and insulin-like growth factor-1, contribute to the development of chronic anemia. This paper aims to review the effect of nutrition, EPO, anabolic hormones, standard HF treatments, and exercise as regulatory mechanisms of chronic anemia and their cardiovascular consequences in patients with HF.</AbstractText><br /><br />© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.<br /><br /><small>Clin Res Cardiol: 03 Sep 2023; epub ahead of print</small></div>

<div><h4>Coronary microvascular dysfunction is a hallmark of all subtypes of MINOCA.</h4><i>Milzi A, Dettori R, Lubberich RK, Reith S, ... Marx N, Burgmaier M</i><br /><b>Introduction</b><br />Myocardial infarction without obstructive coronary artery disease (MINOCA) is a heterogeneous clinical condition presenting with myocardial necrosis not due to an obstruction of a major coronary artery. Recently, a relevant role of coronary microvascular dysfunction (CMD) in the pathogenesis of MINOCA has been suggested; however, data on this are scarce. Particularly, it is unclear if CMD is equally present in all subtypes of MINOCA or differentially identifies one or more of these conditions. Therefore, the aim of this study was to assess CMD in all three coronary vessels of MINOCA patients, relating it with the clinical subtype.<br /><b>Methods</b><br />We retrospectively assessed coronary microvascular function in all three coronary territories by means of angiography-based index of microvascular resistance (aIMR) in 92 patients (64 with working diagnosis of MINOCA, 28 control patients). To further assess the association of CMD with MINOCA subtypes, MINOCA patients were subdivided according to clinical data in coronary cause (n = 13), takotsubo (n = 13), infiltrative or inflammatory cardiomyopathy (n = 9) or unclear (n = 29).<br /><b>Results</b><br />Patients with working diagnosis of MINOCA showed a significantly elevated average aIMR compared to control patients (30.5 ± 7.6 vs. 22.1 ± 5.9, p < 0.001) as a marker of a relevant CMD; these data were consistent in all vessels. Among MINOCA subtypes, no significant difference in average aIMR could be detected between patients with coronary cause (33.2 ± 6.6), takotsubo cardiomyopathy (29.2 ± 6.9), infiltrative or inflammatory cardiomyopathy (28.1 ± 6.8) or unclear cause (30.6 ± 8.5; p = 0.412). Interestingly, aIMR was significantly elevated in the coronary vessel supplying the diseased myocardium compared with other vessels (31.9 ± 11.4 vs. 27.8 ± 8.2, p = 0.049).<br /><b>Conclusion</b><br />Coronary microvascular dysfunction is a hallmark of all MINOCA subtypes. This study adds to the pathophysiological understanding of MINOCA and sheds light into the role of CMD in MINOCA.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 02 Sep 2023; epub ahead of print</small></div>

<div><h4>Implementation of the ESC STEMI guidelines in female and elderly patients over a 20-year period in a large German registry.</h4><i>Riehle L, Gothe RM, Ebbinghaus J, Maier B, ... Landmesser U, Fröhlich GM</i><br /><b>Aims</b><br />We investigated the implementation of new guidelines in ST-segment elevation myocardial infarction (STEMI) patients in a large real-world patient population in the metropolitan area of Berlin (Germany) over a 20-year period.<br /><b>Methods</b><br />From January 2000 to December 2019, a total of 25 792 patients were admitted with STEMI to one of the 34 member hospitals of the Berlin-Brandenburg Myocardial Infarction Registry (B2HIR) and were stratified for sex and age < 75 and ≥ 75 years.<br /><b>Results</b><br />The median age of women was 72 years (IQR 61-81) compared to 61 years in men (IQR 51-71). PCI treatment as a standard of care was implemented in men earlier than in women across all age groups. It took two years from the 2017 class IA ESC STEMI guideline recommendation to prefer the radial access route rather than femoral until > 60% of patients were treated accordingly. In 2019, less than 60% of elderly women were treated via a radial access. While the majority of patients < 75 years already received ticagrelor or prasugrel as antiplatelet agent in the year of the class IA ESC STEMI guideline recommendation in 2012, men ≥ 75 years lagged two years and women ≥ 75 three years behind. Amongst the elderly, in-hospital mortality was 22.6% (737) for women and 17.3% (523) for men (p < 0.001). In patients < 75 years fatal outcome was less likely with 7.2% (305) in women and 5.8% (833) in men (p < 0.001). After adjustment for confounding variables, female sex was an independent predictor of in-hospital mortality in patients ≥ 75 years (OR 1.37, 95% CI 1.12-1.68, p = 0.002), but not in patients < 75 years (p = 0.076).<br /><b>Conclusion</b><br />In-hospital mortality differs considerably by age and sex and remains highest in elderly patients and in particular in elderly females. In these patient groups, guideline recommended therapies were implemented with a significant delay.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 01 Sep 2023; 112:1240-1251</small></div>

<div><h4>Paclitaxel drug-coated balloon-only angioplasty for de novo coronary artery disease in elective clinical practice.</h4><i>Merinopoulos I, Gunawardena T, Corballis N, Bhalraam U, ... Vassiliou VS, Eccleshall SC</i><br /><b>Objective</b><br />We aimed to investigate the safety of drug-coated balloon (DCB)-only angioplasty compared to drug-eluting stent (DES), as part of routine clinical practice.<br /><b>Background</b><br />The recent BASKETSMALL2 trial demonstrated the safety and efficacy of DCB angioplasty for de novo small vessel disease. Registry data have also demonstrated that DCB angioplasty is safe; however, most of these studies are limited due to long recruitment time and a small number of patients with DCB compared to DES. Therefore, it is unclear if DCB-only strategy is safe to incorporate in routine elective clinical practice.<br /><b>Methods</b><br />We compared all-cause mortality and major cardiovascular endpoints (MACE), including unplanned target lesion revascularisation (TLR) of all patients treated with DCB or DES for first presentation of stable angina due to de novo coronary artery disease between 1st January 2015 and 15th November 2019. Data were analysed with Cox regression models and cumulative hazard plots.<br /><b>Results</b><br />We present 1237 patients; 544 treated with DCB and 693 treated with DES for de novo, mainly large-vessel coronary artery disease. On multivariable Cox regression analysis, only age and frailty remained significant adverse predictors of all-cause mortality. Univariable, cumulative hazard plots showed no difference between DCB and DES for either all-cause mortality or any of the major cardiovascular endpoints, including unplanned TLR. The results remained unchanged following propensity score-matched analysis.<br /><b>Conclusion</b><br />DCB-only angioplasty, for stable angina and predominantly large vessels, is safe compared to DES as part of routine clinical practice, in terms of all-cause mortality and MACE, including unplanned TLR.<br /><br />© 2022. The Author(s).<br /><br /><small>Clin Res Cardiol: 01 Sep 2023; 112:1186-1193</small></div>

<div><h4>Incidence and predictors of radial artery occlusion following transradial coronary angiography: the proRadial trial.</h4><i>Schlosser J, Herrmann L, Böhme T, Bürgelin K, ... Neumann FJ, Hochholzer W</i><br /><b>Objectives</b><br />This study investigated the contemporary incidence and predictors of radial artery occlusion as well as the effectiveness of antithrombotic treatment for radial artery occlusion following transradial coronary angiography.<br /><b>Background</b><br />The radial artery is the standard access for coronary angiography and even complex interventions. Postprocedural radial artery occlusion is still a common and significant complication.<br /><b>Methods</b><br />This prospective study enrolled 2004 patients following transradial coronary angiography. After sheath removal, hemostasis was obtained in a standardized fashion. Radial artery patency was evaluated by duplex ultrasonography in all patients. In case of occlusion, oral anticoagulation was recommended and patients were scheduled for a 30-day follow-up including Doppler ultrasonography.<br /><b>Results</b><br />A new-diagnosed radial occlusion was found in 4.6% of patients. The strongest independent predictors of radial occlusion were female sex and active smoking status. In the subgroup of patients with percutaneous coronary interventions, female sex followed by sheath size > 6 French were the strongest predictors of radial occlusion. 76 of 93 patients with radial occlusion received an oral anticoagulation for 30 days. However, reperfusion at 30 days was found in 32% of patients on oral anticoagulation.<br /><b>Conclusion</b><br />The incidence of radial artery occlusion following coronary angiography in contemporary practice appears with 4.6% to be lower as compared to previous cohorts. Female sex and smoking status are the strongest independent predictors of radial occlusion followed by procedural variables. The limited effectiveness of oral anticoagulation for treatment of radial artery occlusion suggests a primarily traumatic than thrombotic mechanism of this complication.<br /><br />© 2022. The Author(s).<br /><br /><small>Clin Res Cardiol: 01 Sep 2023; 112:1175-1185</small></div>

<div><h4>Efficacy and safety of intravenous beta-blockers in acute atrial fibrillation and flutter is dependent on beta-1 selectivity: a systematic review and meta-analysis of randomised trials.</h4><i>Perrett M, Gohil N, Tica O, Bunting KV, Kotecha D</i><br /><b>Background</b><br />Intravenous beta-blockers are commonly used to manage patients with acute atrial fibrillation (AF) and atrial flutter (AFl), but the choice of specific agent is often not evidence-based.<br /><b>Methods</b><br />A prospectively-registered systematic review and meta-analysis of randomised trials (PROSPERO: CRD42020204772) to compare the safety and efficacy of intravenous beta-blockers against alternative pharmacological agents.<br /><b>Results</b><br />Twelve trials comparing beta-blockers with diltiazem, digoxin, verapamil, anti-arrhythmic drugs and placebo were included, with variable risk of bias and 1152 participants. With high heterogeneity (I<sup>2</sup> = 87%; p < 0.001), there was no difference in the primary outcomes of heart rate reduction (standardised mean difference - 0.65 beats/minute compared to control, 95% CI - 1.63 to 0.32; p = 0.19) or the proportion that achieved target heart rate (risk ratio [RR] 0.85, 95% CI 0.36-1.97; p = 0.70). Conventional selective beta-1 blockers were inferior for target heart rate reduction versus control (RR 0.33, 0.17-0.64; p < 0.001), whereas super-selective beta-1 blockers were superior (RR 1.98, 1.54-2.54; p < 0.001). There was no significant difference between beta-blockers and comparators for secondary outcomes of conversion to sinus rhythm (RR 1.15, 0.90-1.46; p = 0.28), hypotension (RR 1.85, 0.87-3.93; p = 0.11), bradycardia (RR 1.29, 0.25-6.82; p = 0.76) or adverse events leading to drug discontinuation (RR 1.03, 0.49-2.17; p = 0.93). The incidence of hypotension and bradycardia were greater with non-selective beta-blockers (p = 0.031 and p < 0.001).<br /><b>Conclusions</b><br />Across all intravenous beta-blockers, there was no difference with other medications for acute heart rate control in atrial fibrillation and flutter. Efficacy and safety may be improved by choosing beta-blockers with higher beta-1 selectivity.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 01 Sep 2023; epub ahead of print</small></div>

<div><h4>Prospective, single-centre evaluation of the safety and efficacy of percutaneous coronary interventions following a decision tree proposing a no-stent strategy in stable patients with coronary artery disease (SCRAP study).</h4><i>Meunier L, Godin M, Souteyrand G, Mottin B, ... Waliszewski M, Allix-Béguec C</i><br /><b>Aim</b><br />We evaluated a decision algorithm for percutaneous coronary interventions (PCI) based on a no-stent strategy, corresponding to a combination of scoring balloon angioplasty (SCBA) and drug-coated balloon (DCB), as a first line approach. Stents were used only in unstable patients, or in case of mandatory bailout stenting (BO-stent).<br /><b>Methods</b><br />From April 2019 to March 2020, 984 consecutive patients, including 1922 lesions, underwent PCI. The 12-month primary end-point was a composite of major adverse cardiac events (MACE) defined as all-cause death, nonfatal myocardial infarction, nonfatal stroke, and target lesion revascularization. Patients were classified into conventional or no-stent strategy groups according to the PCI strategy. In the no-stent strategy group, they were further classified into BO-stent or DCB-only groups. Their metal index was calculated by stent length divided by the total lesion length.<br /><b>Results</b><br />The no-stent strategy was applied in 85% of the patients, and it was successful for 65% of them. MACE occurred in 7.1% of the study population, including 4.2% of all-cause death. Target lesion revascularization was required in 1.4%, 3.6%, and 1.5% of patients in the conventional DES, BO-stent, and DCB-only groups, respectively. MACE occurred more often in the elderly and in those treated with at least one stent (metal index greater than 0).<br /><b>Conclusions</b><br />The no-stent strategy, i.e., revascularization of coronary lesions by SCBA followed by DCB and with DES bailout stenting, was effective and safe at 1 year. This PCI approach was applicable on a daily practice in our cath lab.<br /><b>Trial registration</b><br />This study was registered with clinicaltrials.gov (NCT03893396, first posted on March 28, 2019). Feasibility, safety and efficacy of percutaneous coronary interventions following a decision tree proposing a no-stent strategy in stable patients with coronary artery disease. DES: drug eluting stent; SCBA: scoring balloon angioplasty; BO-stent: at least one stent; DCB: drug coated balloon; BMS: bare metal stent; Bailout (dash lines); MACE: major adverse cardiac event.<br /><br />© 2022. The Author(s).<br /><br /><small>Clin Res Cardiol: 01 Sep 2023; 112:1164-1174</small></div>

<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: 01 Sep 2023; 112:1212-1219</small></div>

<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: 01 Sep 2023; 112:1220-1230</small></div>

<div><h4>Rotational atherectomy of calcified coronary lesions: current practice and insights from two randomized trials.</h4><i>Allali A, Abdel-Wahab M, Elbasha K, Mankerious N, ... Toelg R, Richardt G</i><br /><AbstractText>With growing experience, technical improvements and use of newer generation drug-eluting stents (DES), recent data showed satisfactory acute and long-term results after rotational atherectomy (RA) in calcified coronary lesions. The randomized ROTAXUS and PREPARE-CALC trials compared RA to balloon-based strategies in two different time periods in the DES era. In this manuscript, we assessed the technical evolution in RA practice from a pooled analysis of the RA groups of both trials and established a link to further recent literature. Furthermore, we sought to summarize and analyze the available experience with RA in different patient and lesion subsets, and propose recommendations to improve RA practice. We also illustrated the combination of RA with other methods of lesion preparation. Finally, based on the available evidence, we propose a simple and practical approach to treat severely calcified lesions.</AbstractText><br /><br />© 2022. The Author(s).<br /><br /><small>Clin Res Cardiol: 01 Sep 2023; 112:1143-1163</small></div>

<div><h4>Impact of educational attainment on preventive efforts after myocardial infarction: results of the IPP and NET-IPP trials.</h4><i>Wienbergen H, Fach A, Winzer EB, Schmucker J, ... Hambrecht R, Osteresch R</i><br /><b>Aims</b><br />Educational attainment might impact secondary prevention after myocardial infarction (MI). The purpose of the present study was to compare the rate of risk factors and the efficacy of an intensive prevention program (IPP), performed by prevention assistants and supervised by physicians, in patients with MI and different levels of education.<br /><b>Methods</b><br />In this post hoc analysis of the multicenter IPP and NET-IPP trials, patients with MI were stratified into two groups according to educational attainment: no \"Abitur\" (no A) vs. \"Abitur\" or university degree (AUD). The groups were compared at the time of index MI and after 12-month IPP vs. usual care.<br /><b>Results</b><br />Out of n = 462 patients with MI, 76.0% had no A and 24.0% had AUD. At the time of index, MI rates of obesity (OR 2.4; 95%CI 1.4-4.0), smoking (OR 2.2, 95%CI 1.4-3.6), and physical inactivity (OR 1.6; 95%CI 1.0-2.5) were significantly elevated in patients with no A. At 12 months after index MI, larger improvements of the risk factors smoking and physical inactivity were observed in patients with IPP and no A than in patients with IPP and AUD or with usual care. LDL cholesterol levels were reduced by IPP compared to usual care, with no difference between no A vs. AUD. A matched-pair analysis revealed that high baseline risk was an important reason for the large risk factor reductions in patients with IPP and no A.<br /><b>Conclusion</b><br />The study demonstrates that patients with MI and lower educational level have an increased rate of lifestyle-related risk factors and a 12-month IPP, which is primarily performed by non-physician prevention assistants, is effective to improve prevention in this high-risk cohort.<br /><br />© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.<br /><br /><small>Clin Res Cardiol: 31 Aug 2023; epub ahead of print</small></div>

<div><h4>Cardiovascular events risk in patients with systemic autoimmune diseases: a prognostic systematic review and meta-analysis.</h4><i>Asenjo-Lobos C, González L, Bulnes JF, Roque M, Muñoz Venturelli P, Rodríguez GM</i><br /><b>Background</b><br />Chronic inflammation is considered a risk factor for the development of atherosclerosis and cardiovascular (CV) events. We seek to assess the risk of CV events in patients with Systemic autoimmune diseases (SAD), such as Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA), Psoriasis (Ps) and Ankylosing Spondylitis (AS), compared with the general population.<br /><b>Methods and results</b><br />A systematic search of MEDLINE from inception up to May 2021 was performed. Observational studies including individuals with and without autoimmune diseases (SLE, RA, Ps, AS), which reported a measure of association and variability for the effect of SAD on CV events, were included. The random effects meta-analysis was performed using the Hartung-Knapp-Sidik-Jonkman approach to obtain the pooled estimates. Cardiovascular Events including CV mortality, non-fatal myocardial infarction (MI), non-fatal stroke and coronary revascularization were the main outcomes evaluated. Fifty-four studies were selected, with a total of 24,107,072 participants. The presence of SAD was associated with an increased risk of CV mortality (HR 1.49 [95% CI 1.10-2.03]), non-fatal MI (HR 1.42 [95% CI 1.23-1.62]), and non-fatal stroke (HR 1.47 [95% CI 1.28-1.70]). RA, SLE, and Ps (particularly with arthritis) were significantly associated with a higher risk of MI and stroke. SAD was also associated with an increased risk of Major Adverse Cardiovascular Events (MACE) (HR 1.45 [95% CI 1.16-1.83]).<br /><b>Conclusion</b><br />Patients with SAD present an increased risk of CV morbidity and mortality, which should be considered when establishing therapeutic strategies. These findings support the role of systemic inflammation in the development of atherosclerosis-driven disease.<br /><br />© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.<br /><br /><small>Clin Res Cardiol: 31 Aug 2023; epub ahead of print</small></div>

<div><h4>Added value of arterial stiffness index for the 10-year atherosclerotic cardiovascular disease risk determination in a middle-aged population-based study.</h4><i>Vallée A</i><br /><b>Objective</b><br />Atherosclerotic cardiovascular disease (ASCVD) is considered the leading cause of mortality worldwide. Arterial stiffness, measured by arterial stiffness index (ASI), could be a main predictor in target damage of organs. Uncertainty remains regarding the contribution of ASI to estimated ASCVD risk. This study investigates the added value of ASI in ASCVD risk determination using the general UK Biobank middle-aged population.<br /><b>Methods</b><br />Among 100,598 participants from the UK Biobank population, ASI was assessed and associations between ASCVD risk were stratified by sex and estimated using multiple linear and logistic regressions adjusted for heart rate, physical activity, alcohol status, smocking pack years, BMI categories and CKD.<br /><b>Results</b><br />Males presented higher ASCVD risk than females (8.58% vs. 2.82%, p < 0.001) and higher ASI levels (9.50 m/s vs. 7.00 m/s, p < 0.001). The Youden index was determined at 9.70 m/s in males (p < 0.001) and 10.46 m/s in females (p < 0.001). Among females, participants with ASI > 10.46 m/s showed higher ASCVD risk than others (3.64% vs. 2.56%, p < 0.001), similar results were observed for males (9.92% vs. 7.21%, p < 0.001). In males, ASI showed significant added value information when including overall covariates (AUC = 0.695 vs. AUC = 0.663, p < 0.001). Similar results were observed in females (AUC = 0.693 vs. AUC = 0.687, p = 0.001). In both genders, for the association between ASI and ASCVD risk, nonlinear relationships were observed with higher accuracies than linear models.<br /><b>Conclusion</b><br />Further studies should investigate ASCVD risk stratification management depending on ASI measurement.<br /><br />© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.<br /><br /><small>Clin Res Cardiol: 31 Aug 2023; epub ahead of print</small></div>

<div><h4>Comparison of transcatheter leaflet-approximation and direct annuloplasty in tricuspid regurgitation.</h4><i>Ochs L, Körber MI, Wienemann H, Tichelbäcker T, ... Baldus S, Pfister R</i><br /><b>Background</b><br />Transcatheter repair emerges as a treatment option in patients with tricuspid regurgitation (TR) and high surgical risk.<br /><b>Aims</b><br />This study aimed to compare leaflet-based and annuloplasty-based transcatheter repair in patients with TR.<br /><b>Methods</b><br />In a retrospective analysis consecutive patients undergoing either transcatheter edge-to-edge repair (TEER) or direct annuloplasty (AP) for relevant TR at 2 centers were compared with respect to baseline characteristics, procedural efficacy and safety (death, myocardial infarction, procedure or device-related cardiothoracic surgery, or stroke at 30 days).<br /><b>Results</b><br />161 patients (57% female, median age 79 [75-82] years) with comparable clinical baseline characteristics in the TEER (n = 87) and AP (n = 74) group were examined. Baseline TR grade was significantly less severe in the TEER compared to the AP group (torrential 9.2 vs. 31.1%, p = 0.001). Technical success and improvement of TR grades were not significantly different across groups. In analysis matched for baseline TR severity, reduction of TR grade to less than moderate was significantly more common in the AP group (47.8 vs. 26.1%, p = 0.031). Major or more severe bleeding occurred in 9.2% of TEER and 20.3% of AP patients (p = 0.049) without any fatal bleedings. Major adverse events (MAE) were similar across groups with four patients (4.7%) in the TEER group and five patients (6.9%) in the AP group (p = 0.733) and 6-month survival did not differ significantly.<br /><b>Conclusions</b><br />Differences observed between patients treated with TEER and AP provide first evidence for tailoring distinct transcatheter treatment techniques to individual patient characteristics.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 29 Aug 2023; epub ahead of print</small></div>

<div><h4>Neuroticism and sudden cardiac death: a prospective cohort study from UK biobank.</h4><i>Rhee TM, Lee KY, Choi J, Choi EK, ... Oh S, Lip GYH</i><br /><b>Objective</b><br />There is a paucity of evidence on the risk of sudden cardiac death (SCD) according to the degree of neuroticism. We sought to evaluate the association between neuroticism and the long-term risk of SCD.<br /><b>Methods</b><br />From the UK Biobank nationwide prospective cohort, participants free from previous SCD, ventricular arrhythmias, implantable cardioverter-defibrillator (ICD) insertion, depression, schizophrenia, and bipolar disorder were selected. The 12-item scale of neuroticism measurement (neuroticism score) was categorized into high (≥ 3) and low (< 3) groups. The primary outcome was SCD including ventricular fibrillation (VF) at median 12.6 years of follow-up. The outcomes were compared between the groups using multivariable Cox regression and inverse probability of treatment weighting (IPTW).<br /><b>Results</b><br />A total of 377,563 participants (aged 56.5 ± 8.1, 53.1% women) were analyzed. The high neuroticism score group had a significantly lower risk of SCD (adjusted hazard ratio [aHR] = 0.87, 95% confidence interval [CI] 0.79-0.96, P = 0.007; IPTW-adjusted HR [IPTW-HR] 0.87 [0.77-0.97], P = 0.016) than the low neuroticism score group. The effect of a high neuroticism score on the decreased risk of SCD was more prominent in women (IPTW-HR 0.71 [0.56-0.89], P = 0.003) than in men (IPTW-HR 0.93 [0.82-1.07], P = 0.305, P-for-interaction = 0.043). Sex differences were observed among independent predictors for incident SCD, emphasizing the protective role of a high neuroticism score and moderate-to-vigorous physical activity only in women.<br /><b>Conclusions</b><br />A high neuroticism score was significantly associated with a lower risk of SCD, particularly in women. Efforts to unveil the causal and mechanistic relationship between personality phenotypes and the risk of SCD should be continued.<br /><br />© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.<br /><br /><small>Clin Res Cardiol: 28 Aug 2023; epub ahead of print</small></div>

<div><h4>Topological data analysis to identify cardiac resynchronization therapy patients exhibiting benefit from an implantable cardioverter-defibrillator.</h4><i>Veres B, Schwertner WR, Tokodi M, Szijártó Á, ... Kosztin A, Merkely B</i><br /><b>Background</b><br />Current guidelines recommend considering multiple factors while deciding between cardiac resynchronization therapy with a defibrillator (CRT-D) or a pacemaker (CRT-P). Nevertheless, it is still challenging to pinpoint those candidates who will benefit from choosing a CRT-D device in terms of survival.<br /><b>Objective</b><br />We aimed to use topological data analysis (TDA) to identify phenogroups of CRT patients in whom CRT-D is associated with better survival than CRT-P.<br /><b>Methods</b><br />We included 2603 patients who underwent CRT-D (54%) or CRT-P (46%) implantation at Semmelweis University between 2000 and 2018. The primary endpoint was all-cause mortality. We applied TDA to create a patient similarity network using 25 clinical features. Then, we identified multiple phenogroups in the generated network and compared the groups\' clinical characteristics and survival.<br /><b>Results</b><br />Five- and 10-year mortality were 43 (40-46)% and 71 (67-74)% in patients with CRT-D and 48 (45-50)% and 71 (68-74)% in those with CRT-P, respectively. TDA created a circular network in which we could delineate five phenogroups showing distinct patterns of clinical characteristics and outcomes. Three phenogroups (1, 2, and 3) included almost exclusively patients with non-ischemic etiology, whereas the other two phenogroups (4 and 5) predominantly comprised ischemic patients. Interestingly, only in phenogroups 2 and 5 were CRT-D associated with better survival than CRT-P (adjusted hazard ratio 0.61 [0.47-0.80], p < 0.001 and adjusted hazard ratio 0.84 [0.71-0.99], p = 0.033, respectively).<br /><b>Conclusions</b><br />By simultaneously evaluating various clinical features, TDA may identify patients with either ischemic or non-ischemic etiology who will most likely benefit from the implantation of a CRT-D instead of a CRT-P. Topological data analysis to identify phenogroups of CRT patients in whom CRT-D is associated with better survival than CRT-P. AF atrial fibrillation, CRT cardiac resynchronization therapy, CRT-D cardiac resynchronization therapy defibrillator, CRT-P cardiac resynchronization therapy pacemaker, DM diabetes mellitus, HTN hypertension, LBBB left bundle branch block, LVEF left ventricular ejection fraction, MDS multidimensional scaling, MRA mineralocorticoid receptor antagonist, NYHA New York Heart Association.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 25 Aug 2023; epub ahead of print</small></div>

<div><h4>Detection of atrial fibrillation using an implantable loop recorder in patients with previous cryptogenic stroke: the SPIDER-AF registry (Stroke Prevention by Increasing DEtection Rates of Atrial Fibrillation).</h4><i>Rybak K, D Ancona G, Glück S, Haerer W, Goss F, SPIDER-AF Investigators</i><br /><b>Background</b><br />The use of implantable loop recorder (ILR) to detect atrial fibrillation (AF) in patients with a history of cryptogenic stroke (CS) has seldom been investigated in \"real-world\" settings.<br /><b>Objective</b><br />This study aimed to present the results of the Stroke Prevention by Increasing DEtection Rates of Atrial Fibrillation (SPIDER-AF) registry.<br /><b>Method</b><br />SPIDER is a multicentric, observational registry, including 35 facilities all over Germany. It enrolled outpatients without AF history and with CS before ILR implantation.<br /><b>Results</b><br />We included 500 patients (mean age 63.1 ± 12.7 years), 304 (60.8%) were males, with previous stroke (72.6%) and TIA (27.4%). After inclusion, all were followed for at least 12 months. AF was detected in 133 (26.8%), 25.3% of patients with previous stroke and 29.9% with TIA (p = 0.30). AF was detected after a median of 121.5 days (IQR 40.5-223.0). AF was primarily paroxysmal (95.7% after stroke, 100% after TIA). In 19.5% (n = 26) anticoagulation was not administered after AF detection. Mean CHA2DS2-VASc score (OR 1.22; CI 1.01-1.49; p = 0.037) and age > 70 years (OR 0.41; CI 0.19-0.88; p = 0.0020) correlated with AF. Repeat cerebrovascular events at follow-up (28; 5.6%) correlated with AF (OR = 2.17; CI 1.00-4.72; p = 0.049). AF (p = 0.91) and recurrent events (p = 0.43) occurred similarly in females and males.<br /><b>Conclusions</b><br />In the context of cryptogenic strokes ILRs are a valuable tool for early detection of AF. In a real-world scenario, the anticoagulation therapy remains inadequate despite diagnosed AF in a relevant subset of patients requiring optimization of patient management.<br /><br />© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.<br /><br /><small>Clin Res Cardiol: 23 Aug 2023; epub ahead of print</small></div>

<div><h4>Glycaemic control and insulin therapy are significant confounders of the obesity paradox in patients with heart failure and diabetes mellitus.</h4><i>Fröhlich H, Bossmeyer A, Kazmi S, Goode KM, ... Clark AL, Täger T</i><br /><b>Background</b><br />A high body mass index (BMI) confers a paradoxical survival benefit in patients with heart failure (HF) or diabetes mellitus (DM). There is, however, controversy whether an obesity paradox is also present in patients with HF and concomitant DM. In addition, the influence of glycaemic control and diabetes treatment on the presence or absence of the obesity paradox in patients with HF and DM is unknown.<br /><b>Methods</b><br />We identified 2936 patients with HF with reduced ejection fraction (HFrEF) in the HF registries of the universities of Heidelberg, Germany, and Hull, UK (general sample). Of these, 598 (20%) were treated for concomitant DM (DM subgroup). The relationship between BMI and all-cause mortality was analysed in both the general sample and the DM subgroup. Patients with concomitant DM were stratified according to HbA1c levels or type of diabetes treatment and analyses were repeated.<br /><b>Results</b><br />We found an inverse BMI-mortality relationship in both the general sample and the DM subgroup. However, the obesity paradox was less pronounced in patients with diabetes treated with insulin and it disappeared in those with poor glycaemic control as defined by HbA1c levels > 7.5%.<br /><b>Conclusion</b><br />In patients with HFrEF, a higher BMI is associated with better survival irrespective of concomitant DM. However, insulin treatment and poor glycaemic control make the relationship much weaker.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 22 Aug 2023; epub ahead of print</small></div>

<div><h4>First long-term outcome data for the MicraVR™ transcatheter pacing system: data from the largest prospective German cohort.</h4><i>Sultan A, Scheurlen C, Wörmann J, van den Bruck JH, ... Steven D, Winter S</i><br /><b>Aims</b><br />The MicraVR™ transcatheter pacing system (TPS) has been implemented into clinical routine for several years. The primary recipients are patients in need for VVI pacing due to bradycardia in the setting of atrial fibrillation (AF). Implantation safety and acute success have been proven in controlled studies and registries. So far only few long-term real-life data on TPS exist. We report indication, procedure and outcome data from two high-volume implanting German centers.<br /><b>Methods</b><br />Between 2016 and 2019, 188 (of 303) patients were included. During follow-up (FU), TPS interrogation was performed after 4 weeks and thereafter every 6 months.<br /><b>Results</b><br />Indication for TPS implantation in 159/188 (85%) patients was permanent or intermittent AV block III° in the setting of atrial fibrillation. The mean procedure duration was 50 min [35.0-70.0]. The average acute values after system release were: thresholds: 0.5V [0.38-0.74]/0.24ms; R-wave sensing: 10.0mV [8.1-13.5]; impedance: 650 Ohm [550-783]; RV-pacing demand: 16.9% [0.9-75.9]; and battery status: 3.15 V [3.12-3.16]. During FU of 723.4 ± 597.9 days, neither pacemaker failure nor infections were reported. Long-term FU revealed: thresholds: 0.5V [0.38-0.63]/0.24 ms; sensing: 12.3mV [8.9-17.2]; impedance: 570 Ohm [488-633]; RV-pacing demand: 87.1% [29.5-98.6]; and battery status 3.02 V [3.0-3.1]. Forty-three patients died from not-device-related causes.<br /><b>Conclusion</b><br />This to date largest German long-term dataset for MicraVR™ TPS implantation revealed stable device parameter. Foremost, battery longevity seems to fulfill predicted values despite a significant increase in RV-pacing demand over time and even in patients with consecutive AV-node ablation. Of note, no infections or system failure were observed.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 22 Aug 2023; epub ahead of print</small></div>

<div><h4>Retrospective real-world analysis of adherence and persistence to lipid-lowering therapy in Germany.</h4><i>Koenig W, Lorenz ES, Beier L, Gouni-Berthold I</i><br /><b>Background</b><br />Cardiovascular disease is the leading cause of mortality in Germany. Cardiovascular risk can be mitigated with long-term lipid-lowering therapies (LLTs) that reduce levels of low-density lipoprotein cholesterol. Although effective, risk mitigation is hindered by poor persistence and adherence.<br /><b>Objective</b><br />To investigate real-world persistence and adherence to LLTs through 36 months post-initiation.<br /><b>Methods</b><br />This retrospective cohort study included patients with dyslipidemia who were newly prescribed LLTs between July and December 2017, using anonymized prescription data from the Insight Health™ Patient Insight Tool, and followed up until March 2021. Persistence and adherence to the therapies were stratified by age and sex. The proportion of days covered (PDC) was used to measure adherence.<br /><b>Results</b><br />Patients with dyslipidemia and newly prescribed statins (n = 865,732), ezetimibe (n = 34,490), or anti-proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (anti-PCSK9 mAbs; n = 1940) were included. Persistence to LLTs declined gradually across all treatment subgroups and was lower in women than men. Adherence, calculated as the mean PDC at the end of the analysis period (July 2017‒March 2021) was 0.84, 0.92, and 0.93 for statins, ezetimibe, and anti-PCSK9 mAbs, respectively. Among patients who discontinued treatment, mean treatment duration was 265, 255, and 387 days for statins, ezetimibe, and anti-PCSK9 mAbs, respectively. Only ~ 10% of patients persisted between 201 and 300 days. By Day 300, 71% of patients on statins had discontinued treatment. At 36 months, overall persistence rates were lowest with statins (20.6%), followed by ezetimibe (22.3%) and anti-PCSK9 mAbs (50.9%).<br /><b>Conclusions</b><br />High non-persistence rates were observed across all LLT regimens analyzed, with the lowest persistence rates observed with statins.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 21 Aug 2023; epub ahead of print</small></div>

<div><h4>Micronutrient deficiencies and new-onset atrial fibrillation in a community-based cohort: data from PREVEND.</h4><i>Al-Mubarak AA, Grote Beverborg N, Zwartkruis V, van Deutekom C, ... Rienstra M, Bomer N</i><br /><b>Aim</b><br />Malnutrition has been linked to cardiovascular diseases. Both selenium and iron deficiency have been associated with worse prognosis in patients with heart failure (HF). Yet, little is known about the role of micronutrients in the development of atrial fibrillation (AFib). In this study, we aimed to elucidate the association of micronutrient deficiencies with new-onset AFib.<br /><b>Methods</b><br />Selenium, magnesium, and iron parameters were measured in a well-characterized prospective cohort study (N = 5452). Selenium deficiency was defined as serum selenium < 70 μg/L, iron deficiency as serum ferritin < 30 μg/L, and magnesium deficiency as plasma magnesium < 0.85 mmol/L. New-onset AFib was the primary outcome. Additionally, we tested for previously reported effect-modifiers where applicable.<br /><b>Results</b><br />Selenium, iron, and magnesium deficiency was observed in 1155 (21.2%), 797 (14.6%), and 3600 (66.0%) participants, respectively. During a mean follow-up of 6.2 years, 136 (2.5%) participants developed new-onset AFib. Smoking status significantly interacted with selenium deficiency on outcome (p = 0.079). After multivariable adjustment for components of the CHARGE-AF model, selenium deficiency was associated with new-onset AFib in non-smokers (HR 1.69, 95% CI 1.09-2.64, p = 0.020), but not in smokers (HR 0.78, 95% CI 0.29-2.08, p = 0.619). Magnesium deficiency (HR 1.40, 95% CI 0.93-2.10, p = 0.110) and iron deficiency (HR 0.62, 95% CI 0.25-1.54, p = 0.307) were not significantly associated with new-onset AFib.<br /><b>Conclusion</b><br />Selenium deficiency was associated with new-onset AFib in non-smoking participants. Interventional studies that investigate the effects of optimizing micronutrients status in a population at risk are needed to assess causality, especially in those with selenium deficiency. Micronutrients deficiencies (selenium, iron, and magnesium) have been associated with cardiovascular diseases and mitochondrial dysfunction in human cardiomyocytes. However, it is not known whether these deficiencies are associated with atrial fibrillation. To investigate this question, we measured all three micronutrients in 5452 apparently healthy individuals. After a mean follow-up of 6.2 years, there were 136 participants who developed atrial fibrillation. Participants with selenium deficiency had a significant increased risk to develop atrial fibrillation, as did the participants with two or more deficiencies.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 17 Aug 2023; epub ahead of print</small></div>

<div><h4>Prevalence and prognosis of structural heart disease among athletes with negative T waves and normal transthoracic echocardiography.</h4><i>Conte E, Pizzamiglio F, Dessanai MA, Guarnieri G, ... Tondo C, Andreini D</i><br /><b>Introduction</b><br />The aim of the present study was to evaluate the prevalence and prognosis of structural heart disease (SHD) among competitive athletes with negative T waves without pathological findings at transthoracic echocardiogram.<br /><b>Methods</b><br />From a prospective register of 450 athletes consecutively evaluated during a second-level cardiological examination, we retrospectively identified all subjects with the following inclusion criteria: (1) not previously known cardiovascular disease; (2) negative T waves in leads other than V1-V2; (3) normal transthoracic echocardiogram. Patients underwent cardiac MRI and CT. The primary endpoint was the diagnosis of definite SHD after multimodality imaging evaluation. A follow-up was collected for a combined end-point of sudden death, resuscitated sudden cardiac death and hospitalization for any cardiovascular causes.<br /><b>Results</b><br />A total of 55 competitive athletes were finally enrolled (50 males, 90%) with a mean age of 27.5 ± 14.1 years. Among the population enrolled 16 (29.1%) athletes had a final diagnosis of SHD. At multivariate analysis, only deep negative T waves remained statistically significant [OR (95% CI) 7.81 (1.24-49.08), p = 0.0285]. Contemporary identification of deep negative T waves and complex arrhythmias in the same patients appeared to have an incremental diagnostic value. No events were collected at 49.3 ± 12.3 months of follow-up.<br /><b>Conclusions</b><br />In a cohort of athletes with negative T waves at ECG, cardiac MRI (and selected use of cardiac CT) enabled the identification of 16 (29.1%) subjects with SHD despite normal transthoracic echocardiography. Deep negative T waves and complex ventricular arrhythmias were the only clinical characteristic associated with SHD diagnosis.<br /><br />© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.<br /><br /><small>Clin Res Cardiol: 15 Aug 2023; epub ahead of print</small></div>

<div><h4>Prognostic impact of cancer history in patients undergoing transcatheter mitral valve repair.</h4><i>Kalkan A, Metze C, Iliadis C, Körber MI, Baldus S, Pfister R</i><br /><b>Background</b><br />History of cancer is common in patients undergoing transcatheter mitral valve repair (TMVR).<br /><b>Objectives</b><br />Aim was to examine the impact of cancer history on outcomes after TMVR.<br /><b>Methods</b><br />In patients of a monocentric prospective registry of TMVR history of cancer was retrospectively assessed from records. Associations with 6-week functional outcomes and clinical outcomes during a median follow-up period of 594 days were examined.<br /><b>Results</b><br />Of 661 patients (mean age 79 years; age-range 37-101 years; 56.1% men), 21.6% had a history of cancer with active disease in 4.1%. Compared with non-cancer patients, cancer patients had a similar procedural success rate (reduction of mitral regurgitation to grade 2 or lower 91.6% vs. 88%; p = 0.517) and similar relevant improvement in 6-min walking distance, NYHA class, Minnesota Living with Heart Failure Questionnaire score and Short Form 36 scores. 1-year survival (83% vs. 82%; p = 0.813) and 1-year survival free of heart failure decompensation (75% vs. 76%; p = 0.871) were comparable between cancer and non-cancer patients. Patients with an active cancer disease showed significantly higher mortality compared with patients having a history of cancer (hazard ratio 2.05 [95% CI 1.11-3.82; p = 0.023]) but similar mortality at landmark analysis of 1 year.<br /><b>Conclusion</b><br />TMVR can be performed with equal efficacy in patients with and without cancer and symptomatic mitral regurgitation. Cancer patients show comparable clinical outcome and short-term functional improvement as non-cancer patients. However, longterm mortality was increased in patients with active cancer underlining the importance of patient selection within the heart-team evaluation.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 15 Aug 2023; epub ahead of print</small></div>

<div><h4>Association between three-year mortality after transcatheter aortic valve implantation and paravalvular regurgitation graded by videodensitometry in comparison with visual grading.</h4><i>Elzomor H, Neumann TJ, Boas L, Ruile P, ... Serruys P, Schoechlin S</i><br /><b>Background</b><br />Estimation of regurgitant fraction by videodensitometry (VD-AR) of aortic root angiograms is a new tool for objective grading of paravalvular regurgitation (PVR) after transcatheter aortic valve implantation (TAVI). Stratification with boundaries at 6% and 17% has been proposed to reflect \"none/trace\", \"mild\" and \"moderate or higher\" PVR.<br /><b>Objective</b><br />We sought to investigate the association of strata of VD-AR with 3-year mortality and to compare VD-AR with visual grading of angiograms.<br /><b>Methods</b><br />We interrogated our database for patients undergoing transfemoral TAVI from 2008 to 2018. Vital status of the patients was obtained from population registers. To test differences in survival and estimate adjusted hazard ratios (HRs) we fitted Cox models.<br /><b>Results</b><br />Our retrospective study included 699 patients with evaluable angiograms at completion of the TAVI procedure. Cumulative 3-year mortality was 35.0% in 261 (37.3%) patients with VD-AR < 6%, 33.9% in 325 (46.5%) patients with VD-AR between 6 and 17% (HR [95% confidence interval] 1.06 [0.80-1.42]; P = 0.684) and 47.2% in 113 (16.2%) patients with VD-AR > 17% (HR 1.57 [1.11-2.22]; P = 0.011). Visually, PVR was graded as \"none/trace\" in 470 (67.2%) patients, as \"mild\" in 219 (31.3%) and as \"moderate\" in 10 (1.4%). Both mild PVR and moderate PVR on visual grading were significantly associated with mortality (HRs 1.31 [1.12-1.54]; P = 0.001 and 1.92 [1.13-3.24]; P = 0.015; respectively).<br /><b>Conclusions</b><br />VD-AR > 17%, but not VD-AR 6-17%, was independently associated with mortality. Compared with subjective visual evaluation, VD-AR resulted in a smaller proportion of patients with PVR classified as prognostically relevant.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 09 Aug 2023; epub ahead of print</small></div>

<div><h4>Predictors of long-term adverse outcomes after successful chronic total occlusion intervention: physiology or morphology?</h4><i>Elbasha K, Alotaibi S, Heyer H, Mankerious N, ... Richardt G, Allali A</i><br /><b>Background</b><br />Quantitative flow ratio (QFR) and target-vessel SYNTAX score (tvSS) are novel indices used to assess lesion physiology and morphology in percutaneous coronary intervention (PCI). Their prognostic implication after successful recanalization of coronary chronic total occlusion (CTO) is unknown.<br /><b>Objectives</b><br />To investigate the prognostic value of QFR measured immediately after successful CTO-recanalization in predicting vessel-oriented adverse events, and to compare it with the pre-procedural morphological tvSS.<br /><b>Methods</b><br />QFR was measured offline after successful CTO-PCIs in a single center. We grouped the patients according to a cut-off value of post-PCI QFR (0.91). The primary outcome was target-vessel failure (TVF) at 2 years.<br /><b>Results</b><br />Among 470 CTO lesions performed during the study period, 324 were eligible for QFR analysis (258 with QFR ≥ 0.91 and 66 with QFR < 0.91). The mean age of the study population was 68.3 ± 10.7 years. The low QFR group had a lower left ventricular ejection fraction (45.8 ± 13.9% vs. 49.8 ± 12.4%, p = 0.025) and a higher rate of atrial fibrillation (19.7% vs. 11.2%, p = 0.020). The mean tvSS was 12.8 ± 4.8, and it showed no significant difference in both groups (13.6 ± 5.1 vs. 12.6 ± 4.6, p = 0.122). Patients with low post-CTO QFR had a trend to develop more TVF at 2 years (21.2% vs. 12.4%, HR 1.74; 95% CI 0.93-3.25, p = 0.086). Low post-CTO QFR failed to predict 2-year TVF (aHR 1.67; 95% CI 0.85-3.29, p = 0.136), while pre-procedural tvSS was an independent predictor for 2-year TVF (aHR 1.06; 95% CI 1.01-1.13, p = 0.030).<br /><b>Conclusion</b><br />We found a limited prognostic value of immediate physiological assessment using QFR after successful CTO intervention. Pre-procedure morphological characteristics of CTO lesions using tvSS can play a role in predicting long-term adverse events.<br /><br />© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.<br /><br /><small>Clin Res Cardiol: 04 Aug 2023; epub ahead of print</small></div>

<div><h4>Morphological and functional types of tricuspid regurgitation: prognostic value in patients undergoing tricuspid annuloplasty during left-sided valvular surgery.</h4><i>Tse YK, Li HL, Ren QW, Huang JY, ... Flachskampf FA, Yiu KH</i><br /><b>Background</b><br />The nonuniform benefit of tricuspid annuloplasty may be explained by the proportionality of tricuspid regurgitation (TR) severity to right ventricular (RV) area. The purpose of this study was to delineate distinct morphological phenotypes of functional TR and investigate their prognostic implications in patients undergoing tricuspid annuloplasty during left-sided valvular surgery.<br /><b>Methods</b><br />The ratios of pre-procedural effective regurgitant orifice area (EROA) with right ventricular end-diastolic area (RVDA) were retrospectively assessed in 290 patients undergoing tricuspid annuloplasty. Based on optimal thresholds derived from penalized splines and maximally selected rank statistics, patients were stratified into proportionate (EROA/RVDA ratio ≤ 1.74) and disproportionate TR (EROA/RVDA ratio > 1.74).<br /><b>Results</b><br />Overall, 59 (20%) and 231 (80%) patients had proportionate and disproportionate TR, respectively. Compared to those with proportionate TR, patients with disproportionate TR were older, had a higher prevalence of atrial fibrillation, lower pulmonary pressures, more impaired RV function, and larger tricuspid leaflet tenting area. Over a median follow-up of 4.1 years, 79 adverse events (47 heart failure hospitalizations and 32 deaths) occurred. Patients with disproportionate TR had higher rates of adverse events than those with proportionate TR (32% vs 10%; P = 0.001) and were independently associated with poor outcomes on multivariate analysis. TR proportionality outperformed guideline-based classification of TR severity in outcome prediction and provided incremental prognostic value to both the EuroSCORE II and STS score (incremental χ<sup>2</sup> = 6.757 and 9.094 respectively; both P < 0.05).<br /><b>Conclusions</b><br />Disproportionate TR is strongly associated with adverse prognosis and may aid patient selection and risk stratification for tricuspid annuloplasty with left-sided valvular surgery.<br /><br />© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.<br /><br /><small>Clin Res Cardiol: 04 Aug 2023; epub ahead of print</small></div>

<div><h4>Evaluation of right-ventricular function by two-dimensional echocardiography and two-dimensional speckle-tracking echocardiography in patients with successful RCA CTO recanalization.</h4><i>Blessing R, Drosos I, Molitor M, Münzel T, ... Gori T, Dimitriadis Z</i><br /><b>Objectives</b><br />Chronic total occlusion (CTO) of the right coronary artery (RCA) is common in patients with coronary artery disease. Although revascularization techniques and success rates have improved significantly in recent years, there are still no studies investigating possible effects of successful recanalization of RCA CTO on the right-ventricular (RV) function. With this study, we aimed to evaluate RV function after recanalization of the RCA by two-dimensional transthoracic echocardiography (2DE) and additional two-dimensional speckle-tracking echocardiography (2DSTE).<br /><b>Methods and results</b><br />Our analysis included 102 patients undergoing successful RCA CTO recanalization at the University Medical Center of Mainz. All patients underwent 2DE and 2DSTE to assess RV function before PCI procedure and 6 months after successful revascularization. We found an altered RV function in our collective at baseline assessed by 2DSTE with a significant improvement at 6 month follow-up (baseline RV free wall strain: - 20.7 [- 6.3 to - 32.0] % vs. - 23.4 [- 8.3 to - 39.3] % at follow-up, p < 0.001 and baseline RV global strain - 15.9 [- 6.0 to - 25.7] % vs. - 17.9 [- 7.0 to - 29.5] % at follow-up, p < 0.001).<br /><b>Conclusion</b><br />RV function was altered in patients with RCA CTO and showed significant improvement after successful recanalization. We also noticed an improvement in patient-reported clinical symptoms. Our study suggests that CTO procedure is a beneficial treatment option in symptomatic patients with RCA CTO.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 01 Aug 2023; epub ahead of print</small></div>

<div><h4>Arrhythmias and laboratory abnormalities after an electrical accident: a single-center, retrospective study of 333 cases.</h4><i>Seyfrydova M, Rokyta R, Rajdl D, Huml M</i><br /><b>Background</b><br />Even though electrical injuries are common in the emergency room, guidelines, consensus, and general recommendations for the management of these patients do not exist in Europe. Documented cases of delayed arrhythmias are rare and their connection with electrical injury has not been fully confirmed. We also use cardio-specific markers for the risk stratification of myocardial injury, but there is no significant study referring to their utility in this clinical situation. These reasons led us to retrospectively analyze all cases of electrical injuries over 23 years to determine the prevalence of cardiac arrhythmias (mainly malignant arrhythmias and delayed arrhythmias).<br /><b>Methods</b><br />We retrospectively searched all patients admitted to the University Hospital in Pilsen, CZ, with a diagnosis of electric injury (ICD diagnostic code T754) from 1997 to 2020. The hospital´s information system was used to research the injury; data were drawn from patient medical records.<br /><b>Results</b><br />We identified 333 cases of electrical injury in our hospital. Men accounted for about two-thirds, and women one-third. Children accounted for about one-third of cases. Most were low-voltage injuries (< 1000 V, 91.6%). All participants had an initial ECG, and 77.5% of patients had continuous ECG monitoring, usually lasting 24 h. Cardiac arrhythmias were noticed in 39 patients (11.7%). The most frequent arrhythmias were: ventricular fibrillation, sinus tachycardia, bradycardia and arrhythmia, atrial fibrillation, and supraventricular tachycardia. The ECG showed cardiac conduction abnormalities in 28 patients (8.1%), and ten patients (3%) had supraventricular or ventricular extrasystoles. In ten cases (3%), we found changes in ST segments and T waves on the initial ECG. Thirty-one patients (9.3%) suffered a loss of consciousness and 50 patients (15.02%) reported paresthesia. The most frequent ion disbalances were hypokalemia (18%) and hypocalcemia (3.3%). Patients with an ion disbalance had significantly more arrhythmias and newly diagnosed cardiac conduction abnormalities. Troponin levels (cTnI or hs-cTnT) were measured in 258 cases (77.48%) and found to be elevated above the 99th percentile in 19 cases (5.7%). Almost one-third of patients had burns of various degrees of seriousness, and 41 patients (12.3%) had concomitant traumatic injuries. Eleven patients underwent pre-hospital resuscitation, three died in the hospital, and another died as result of intracranial hemorrhage.<br /><b>Conclusion</b><br />All malignant arrhythmias occurred immediately after the electrical injury, delayed life-threatening arrhythmias were not observed, and no predictive factors of malignant arrhythmias were found. While elevations of cardiac troponins were observed sporadically, they did not appear helpful for risk stratification. In patients with arrhythmias, ion disbalance may be more critical. We concluded that asymptomatic, uninjured adult and pediatric patients with normal initial ECG findings do not need continuous ECG monitoring and may be discharged home. Recommendations for high-risk patients and patients with mild ECG abnormalities at admission are less obvious.<br /><br />© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.<br /><br /><small>Clin Res Cardiol: 01 Aug 2023; epub ahead of print</small></div>

<div><h4>Feasibility and outcome of third-generation transcatheter aortic valve implantation in patients with extra-large aortic annulus.</h4><i>Hof A, Wienemann H, Veulemans V, Ludwig S, ... Adam M, Mauri V</i><br /><b>Background</b><br />Many patients in need for transcatheter aortic valve implantation (TAVI) present with an aortic annulus size larger than recommended by the manufacturer\'s instructions for use (IFU).<br /><b>Aims</b><br />To investigate procedural and short-term safety and efficacy of TAVI in patients with extra-large annuli (ELA).<br /><b>Methods</b><br />30-day clinical outcome and valve performance as defined by VARC 3 of 144 patients with an aortic annulus size exceeding the permitted range were compared to a propensity-score matched control cohort of patients with an aortic annulus size consistent with the IFU.<br /><b>Results</b><br />Area and perimeter was 730.4 ± 53.9 mm<sup>2</sup> and 96.7 ± 6.5 mm in the ELA group. Technical (96.5% vs. 94.4%) and device success (82.3% vs. 84.5%) were comparable in patients with ELA (annulus area 730.4 ± 53.9 mm<sup>2</sup>) and matched controls (annulus area 586.0 ± 48.2 mm<sup>2</sup>). There was no significant difference in 30-day mortality rate, major intraprocedural complications, type 3 or 4 bleedings, major vascular complications, or stroke. Moderate paravalvular leakage (PVL) occurred more frequent in the ELA group (8.9% vs 2.2%; p = 0.02). The rate of new pacemaker implantation was 7.0% in the ELA cohort and 15.0% in the control cohort, respectively (p = 0.05).<br /><b>Conclusion</b><br />Treatment of ELA patients with third-generation TAVI prostheses is feasible and safe, providing similar device success and complication rates as in matched controls with regular-sized aortic annulus. Post-interventional pacemaker implantation rates were low compared to the control group, yet incidence of moderate PVL remains problematic in ELA patients.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 31 Jul 2023; epub ahead of print</small></div>

<div><h4>Optical coherence tomography-guided versus angiography-guided percutaneous coronary intervention in acute coronary syndrome: a meta-analysis.</h4><i>Macherey-Meyer S, Meertens MM, Heyne S, Braumann S, ... Adler C, Lee S</i><br /><b>Background</b><br />Percutaneous coronary intervention (PCI) is standard of care in patients with acute coronary syndrome (ACS) suitable for interventional revascularization. Intracoronary imaging by optical coherence tomography (OCT) expanded treatment approaches adding diagnostic information and contributing to stent optimization.<br /><b>Objectives</b><br />This meta-analysis aimed to assess the effects of OCT-guided vs. angiography-guided PCI in treatment of ACS.<br /><b>Methods</b><br />A structured literature search was performed. All controlled trials evaluating OCT-guided vs. angiography-guided PCI in patients with ACS were eligible. The primary end point was major adverse cardiac events (MACE).<br /><b>Results</b><br />Eight studies enrolling 2612 patients with ACS were eligible. 1263 patients underwent OCT-guided and 1,349 patients angiography-guided PCI. OCT guidance was associated with a 30% lower likelihood of MACE (OR 0.70, 95% CI 0.53-0.93, p = 0.01, I<sup>2</sup> = 1%). OCT-guided PCI was also associated with significantly decreased cardiac mortality (OR 0.49, 95% CI 0.25-0.96, p = 0.04, I<sup>2</sup> = 0%). There was no detectable difference in all-cause mortality (OR 1.08, 95% CI 0.51-2.31, p = 0.83, I<sup>2</sup> = 0). Patients in OCT-guided group less frequently required target lesion revascularization (OR 0.26, 95% CI 0.07-0.95, p = 0.04, I<sup>2</sup> = 0%). Analysis of myocardial infarction did not result in significant treatment differences. In subgroup or sensitivity analysis the observed advantages of OCT-guided PCI were not replicable.<br /><b>Conclusion</b><br />The evidence suggests that PCI guidance with OCT in ACS decreases MACE, cardiac death and target lesion revascularization compared to angiography. On individual study level, in subgroup or sensitivity analyses these advantages were not thoroughly replicable.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 31 Jul 2023; epub ahead of print</small></div>

<div><h4>Age- and sex-based normal reference ranges of the cardiac time intervals: the Copenhagen City Heart Study.</h4><i>Alhakak AS, Olsen FJ, Skaarup KG, Lassen MCH, ... Møgelvang R, Biering-Sørensen T</i><br /><b>Background</b><br />Color tissue Doppler imaging (TDI) M-mode can be used to measure the cardiac time intervals including the isovolumic contraction time (IVCT), the left ventricular ejection time (LVET), the isovolumic relaxation time (IVRT), and the combination of all the cardiac time intervals in the myocardial performance index (MPI) defined as [(IVCT + IVRT)/LVET]. The aim of this study was to establish normal age- and sex-based reference ranges for the cardiac time intervals.<br /><b>Methods and results</b><br />A total of 1969 participants free of cardiovascular diseases and risk factors from the general population with limited age range underwent an echocardiographic examination including TDI. The median age was 46 years (25th-75th percentile: 33-58 years), and 61.5% were females. In the entire study population, the IVCT was observed to be 40 ± 10 ms [95% prediction interval (PI) 20-59 ms], the LVET 292 ± 23 ms (95% PI 248-336 ms), the IVRT 96 ± 19 ms (95% PI 59-134 ms) and MPI 0.47 ± 0.09 (95% PI 0.29-0.65). All the cardiac time intervals differed significantly between females and males. With increasing age, the IVCT increased in females, but not in males. The LVET did not change with age in both sexes, while the IVRT increased in both sexes with increasing age. Furthermore, we developed regression equations relating the heart rate to the cardiac time intervals and age- and sex-based normal reference ranges corrected for heart rate.<br /><b>Conclusion</b><br />In this study, we established normal age- and sex-based reference ranges for the cardiac time intervals. These normal reference ranges differed significantly with sex.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 31 Jul 2023; epub ahead of print</small></div>

<div><h4>Protective effect of vaccination on the risk of cardiovascular disease after SARS-CoV-2 infection.</h4><i>Song J, Choi S, Jeong S, Chang JY, ... Lee S, Park SM</i><br /><b>Objective</b><br />This study investigated the incidence of CVDs after COVID-19.<br /><b>Methods</b><br />Data for 2,146,130 infected people were collected, including the vaccination status. COVID-19 patients were classified according to the number of the received vaccine doses: no, first, second, and ≥ third. To evaluate the short-term risk of CVDs after infection, adjusted odds ratios (aOR) and 95% confidence intervals (CIs) were calculated by multivariable logistic regression analysis after adjustments for covariates.<br /><b>Results</b><br />Compared to non-infected people, aORs [95% CIs; p value] for CVDs within a month after infection were 2.80 [2.64-2.97; < 0.001] in overall infected people and 4.62 [4.23-5.05; < 0.001], 4.20 [3.45-5.11; < 0.001], 2.79 [2.55-3.05; < 0.001], and 2.07 [1.91-2.24; < 0.001] in those who were infected after receiving no, first, second, and ≥ third vaccine doses, respectively. Among participants who received second doses of vaccine prior to contracting COVID-19, the aOR in those vaccinated with only the mRNA-based vaccine (BNT162b2 and mRNA-1273; Reference) was lower than those vaccinated with the virus-derived vaccine (ChAdOx1 nCov-19 and AD26.COV2-S; aOR 1.25 [1.06-1.48; < 0.01]).<br /><b>Conclusion</b><br />Although COVID-19 increased the CVD risk, the inverse association in the risk of CVDs according to vaccine doses was significant in a dose-response manner. Our findings suggest that ≥ second doses of the COVID-19 vaccine prevent the risk of CVDs after SARS-CoV-2 infection. In 2,146,130 infected adults (≥ 20 years), the inverse association in the short-term risk of cardiovascular diseases, including coronary heart disease and stroke, according to vaccine doses received was significant in a dose-response manner.<br /><br />© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.<br /><br /><small>Clin Res Cardiol: 31 Jul 2023; epub ahead of print</small></div>

<div><h4>New-onset atrial fibrillation after percutaneous patent foramen ovale closure: a meta-analysis.</h4><i>Jurczyk D, Macherey-Meyer S, Rawish E, Stiermaier T, ... Frerker C, Schmidt T</i><br /><b>Background</b><br />The exact incidence and predictors of new-onset atrial fibrillation (AF) after percutaneous closure of patent foramen ovale (PFO) are unknown.<br /><b>Objective</b><br />We sought to find post-procedural AF incidence rates and differences due to different screening strategies and devices.<br /><b>Methods</b><br />A systematic search was conducted in Cochrane, MEDLINE and EMBASE. Controlled trials fulfilling the inclusion criteria were included into this meta-analysis. The incidence of new-onset AF was the primary outcome. Further parameters were surveillance strategy, device type, AF treatment and neurological events. New AF was determined as early onset within one month after implantation and late thereafter.<br /><b>Results</b><br />8 controlled trials and 16 cohort studies were eligible for quantitative analysis. 7643 patients received percutaneous PFO closure after cryptogenic stroke or transient ischaemic attack, 117 with other indications, whereas 1792 patients formed the control group. Meta-analysis of controlled trials showed an AF incidence of 5.1% in the interventional and 1.6% in the conservative arm, respectively (OR 3.17, 95% CI 1.46-6.86, P = 0.03, I<sup>2</sup> = 55%). 4.7% received high-quality surveillance strategy with Holter-ECG or Loop recorder whereby AF incidence was overall higher compared to the low-quality group with 12-lead ECG only (3.3-15% vs. 0.2-4.3%). Heterogeneous results on time of AF onset were found, limited by different follow-up strategies. CardioSEAL and Starflex seemed to have higher AF incidences in early and late onset with 4.5% and 4.2%, respectively.<br /><b>Conclusion</b><br />Percutaneous PFO closure led to higher AF post-procedural incidence compared to the conservative strategy. Heterogeneity in surveillance and follow-up strategy limited the generalizability.<br /><b>Trial registration</b><br />Registered on PROSPERO (CRD42022359945).<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 29 Jul 2023; epub ahead of print</small></div>

<div><h4>A meta-analysis evaluating efficacy and safety of colchicine for prevention of major cardiovascular events in patients with coronary artery disease.</h4><i>Chen T, Liu G, Yu B</i><br /><b>Background</b><br />Inflammatory plays a key role in the development of coronary artery disease (CAD). Colchicine as an anti-inflammatory treatment for CAD has attracted much attention, its efficacy and safety are controversial and deserved further exploration.<br /><b>Methods and results</b><br />To evaluate the efficacy and safety of colchicine for patients with CAD, relevant randomized controlled trials (RCTs) were identified by searching several databases including PubMed, Web of Science, and EMBASE from January 1992 to May 2022. Fourteen eligible trials of colchicine therapy include populations with chronic coronary syndrome (CCS) (N = 2), acute coronary syndrome (ACS) (N = 5), and percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) (N = 7), and involve a total of 13,235 patients which include 6654 subjects in colchicine group and 6581 subjects in the respective control arms. The outcome was reported as odds ratio (OR) and 95% confidence interval (CI), as the relative measure of association. Overall, the incidences of major adverse cardiovascular events (MACEs) (OR 0.65; 95% CI 0.54-0.77, p < 0.01), new ACS (OR 0.68; 95% CI 0.57-0.81, p < 0.01), coronary revascularization (OR 0.65; 95% CI 0.53-0.78, p < 0.01), and stroke (OR 0.51; 95% CI 0.32-0.82, p < 0.01), were lower in the colchicine group than in the placebo arm. We did not find a significant reduction in the incidence of atrial fibrillation (OR 0.84; 95% CI 0.68-1.04, p = 0.11), all-cause mortality (OR 1.06; 95% CI 0.83-1.35, p = 0.83), cardiovascular mortality (OR 0.77; 95% CI 0.52-1.15, p = 0.21). However, we found that colchicine did increase non-cardiovascular mortality (OR 1.44; 95% CI 1.04-2.01, p = 0.03). Although the incidence of gastrointestinal events in the colchicine treatment group was higher than that in the placebo arms (OR 2.08; 95% CI 1.39-3.12, p < 0.01), the symptoms disappeared rapidly after drug withdrawal and could be tolerated by most patients. Colchicine did not increase the incidence of infections (OR 1.42; 95% CI 0.82-2.46, p = 0.22), pneumonia (OR 1.55; 95% CI 0.58-4.18, p = 0.39), cancers (OR 0.98; 95% CI 0.79-1.22, p = 0.88), bleeding (OR 1.14; 95% CI 0.41-3.14, p = 0.80).<br /><b>Conclusions</b><br />Colchicine is an effective, relatively safe drug that could be considered for the treatment of CAD. However, we need to pay attention to the increasing occurrence of non-cardiovascular mortality and infection especially pneumonia possibly caused by colchicine. Efficacy and safety of colchicine for patients with CAD. CAD coronary artery disease; RCTs randomized controlled trials; OR odds ratio; MACEs major adverse cardiovascular events; ACS acute coronary syndrome; NNT number needed to treat; NNH number needed to harm.<br /><br />© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.<br /><br /><small>Clin Res Cardiol: 28 Jul 2023; epub ahead of print</small></div>

<div><h4>Early versus delayed coronary angiography in patients with out-of-hospital cardiac arrest and no ST-segment elevation: a systematic review and meta-analysis of randomized controlled trials.</h4><i>Hamidi F, Anwari E, Spaulding C, Hauw-Berlemont C, ... Preusch MR, Zelniker TA</i><br /><b>Background</b><br />Recent randomized controlled trials did not show benefit of early/immediate coronary angiography (CAG) over a delayed/selective strategy in patients with out-of-hospital cardiac arrest (OHCA) and no ST-segment elevation. However, whether selected subgroups, specifically those with a high pretest probability of coronary artery disease may benefit from early CAG remains unclear.<br /><b>Methods</b><br />We included all randomized controlled trials that compared a strategy of early/immediate versus delayed/selective CAG in OHCA patients and no ST elevation and had a follow-up of at least 30 days. The primary outcome of interest was all-cause death. Odds ratios (OR) were calculated and pooled across trials. Interaction testing was used to assess for heterogeneity of treatment effects.<br /><b>Results</b><br />In total, 1512 patients (67 years, 26% female, 23% prior myocardial infarction) were included from 5 randomized controlled trials. Early/immediate versus delayed/selective CAG was not associated with a statistically significant difference in odds of death (OR 1.12, 95%-CI 0.91-1.38), with similar findings for the composite outcome of all-cause death or neurological deficit (OR 1.10, 95%-CI 0.89-1.36). There was no effect modification for death by age, presence of a shockable initial cardiac rhythm, history of coronary artery disease, presence of an ischemic event as the presumed cause of arrest, or time to return of spontaneous circulation (all P-interaction > 0.10). However, early/immediate CAG tended to be associated with higher odds of death in women (OR 1.52, 95%-CI 1.00-2.31, P = 0.050) than in men (OR 1.04, 95%-CI 0.82-1.33, P = 0.74; P-interaction 0.097).<br /><b>Conclusion</b><br />In OHCA patients without ST-segment elevation, a strategy of early/immediate versus delayed/selective CAG did not reduce all-cause mortality across major subgroups. However, women tended to have higher odds of death with early CAG.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 27 Jul 2023; epub ahead of print</small></div>

<div><h4>Adherence to oral anticoagulation measured by electronic monitoring in a Belgian atrial fibrillation population.</h4><i>Knaepen L, Delesie M, Vijgen J, Dendale P, ... Desteghe L, Heidbuchel H</i><br /><b>Introduction</b><br />Stroke prevention using oral anticoagulation (OAC) is the first management priority in atrial fibrillation (AF). Despite the importance of good therapy adherence, real-world adherence is still suboptimal. Patient education and adherence monitoring with new technologies are recommended. The main purpose of this sub-analysis of the AF-EduCare trial was to evaluate the effect of personalized follow-up strategies on adherence to OAC.<br /><b>Methods</b><br />Regimen adherence was monitored by the electronic Medication Event Monitoring System cap at the start of the trial (M1) and after 12 months (M2), each for three months. Patients were part of one of three education groups (In-person, Online or App-based) or the standard care (SC) group. All are qualified for OAC therapy.<br /><b>Results</b><br />A total of 768 patients were evaluated (11.8% SC vs. 86.8% any education group, mean age: 70.1 ± 7.9 years). Patients were taking non-vitamin K OAC (once daily 53.8%; twice daily 35.9%) or vitamin K antagonists (9.4%), equally distributed over the different study arms (p = 0.457). Mean therapy adherence was high (M1:93.8 ± 10.8%; M2:94.1 ± 10.1%). During both monitoring periods, the education group scored significantly higher than SC (M1:94.2 ± 10.0% vs. 91.3 ± 15.0%; p = 0.027; M2:94.4 ± 9.3% vs. 91.6 ± 14.0%; p = 0.006). More patients in the In-person and Online groups were able to keep or improve their adherence to > 90% compared to the SC.<br /><b>Conclusion</b><br />Overall adherence to OAC in all study groups, even in SC, was very high, without attrition over time. Nevertheless, targeted education led to a small but significantly improved adherence compared to SC.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 27 Jul 2023; epub ahead of print</small></div>

<div><h4>Sex-specific inequalities in the use of drug-coated balloons for small coronary artery disease: a report from the BASKET-SMALL 2 trial.</h4><i>Rubini Gimenez M, Scheller B, Farah A, Ohlow MA, ... Kaiser C, Jeger RV</i><br /><b>Background:</b><br/>and objectives</b><br />Recent data have established non-inferiority of drug-coated balloons (DCB) compared to drug-eluting stents (DES) for treatment of small-vessel coronary artery disease. Since coronary vessels in women might have anatomical and pathophysiological particularities, the safety of the DCB strategy among women compared to men needs to be assessed in more detail.<br /><b>Methods</b><br />In BASKET-SMALL 2, patients with de novo lesions in coronary vessels < 3 mm and an indication for percutaneous coronary intervention were randomly allocated (1:1) to DCB vs. DES after successful lesion preparation. The primary objective of the randomized trial was to establish non-inferiority of DCB vs. DES regarding major adverse cardiac events (MACE; i.e., cardiac death, non-fatal myocardial infarction, and target vessel revascularization) after 12 months. The aim of the current sub-analysis is to evaluate whether the DCB strategy is equally safe among women and men after 12 and 36 months.<br /><b>Results</b><br />Among 758 randomized patients, 382 were assigned to DCB (23% women) and 376 to DES (30% women). In general, women were older, had more often diabetes mellitus and renal insufficiency, and presented more often with an acute coronary syndrome, whereas men were more often smokers, had multivessel disease and a previous history of acute myocardial infarction, and received a treatment with a statin. After 3 years, the primary clinical end point was not significantly different between groups (13% women vs. 16% men, HR 0.82; 95% CI 0.52-1.30; p = 0.40). There was no interaction between sex and coronary intervention strategy regarding MACE at 36 months (10% women vs. 16% men in DCB, 16% women vs. 15% men in DES; p<sub>interaction</sub> = 0.31).<br /><b>Conclusion</b><br />In small native coronary artery disease, there was no statistically significant effect of sex on the difference between DCB and DES regarding MACE up to 36 months.<br /><b>Clinical trial registration</b><br />URL: http://www.<br /><b>Clinicaltrials</b><br />gov . Unique identifier: NCT01574534. CAD coronary artery disease, MACE major adverse cardiovascular events, HR Hazard ratio, DCB drug-coated balloon, DES drug-eluting stent.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 26 Jul 2023; epub ahead of print</small></div>

<div><h4>Large-scale lipidomics profiling reveals characteristic lipid signatures associated with an increased cardiovascular risk.</h4><i>Harm T, Dittrich K, Brun A, Fu X, ... Lämmerhofer M, Gawaz MP</i><br /><b>Background:</b><br/>and aims</b><br />Patients with cardiovascular disease (CVD) are at high risk to develop adverse events. The distinct risk of developing adverse cardiovascular (CV) events is not solely explained by traditional risk factors. Platelets are essentially involved in progression of CVD including coronary artery disease (CAD) and platelet hyperreactivity leads to development of adverse CV events. Alterations in the platelet lipidome lead to platelet hyperresponsiveness and thus might alter the individual risk profile. In this study, we investigate the platelet lipidome of CAD patients by untargeted lipidomics and elucidate alterations in the lipid composition of patients with adverse CV events.<br /><b>Methods</b><br />We characterized the platelet lipidome in a large consecutive CAD cohort (n = 1057) by an untargeted lipidomics approach using liquid chromatography coupled to mass spectrometry.<br /><b>Results</b><br />The platelet lipidome in this study identified 767 lipids and characteristic changes occurred in patients with adverse CV events. The most prominent upregulated lipids in patients with cardiovascular events primarily belong to the class of phospholipids and fatty acyls. Further, upregulated platelet lipids are associated with an increased cardiovascular or bleeding risk and independently associated with adverse events. In addition, alterations of the platelet lipidome are associated with modulation of in vitro platelet functions.<br /><b>Conclusions</b><br />Our results reveal that the composition of the platelet lipidome is altered in CVD patients with an increased cardiovascular risk and distinct platelet lipids may indicate adverse events. Results of this study may contribute to improved risk discrimination and classification for cardiovascular events in patients with CVD. Main findings of this study and hypothetical impact of altered platelet lipid signatures in patients with adverse cardiovascular events on platelet function and clinical outcome. LPE lysophosphatidylethanolamines, CAR acylcarnitines, FA fatty acids.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 20 Jul 2023; epub ahead of print</small></div>

<div><h4>Comparison of contemporary transcatheter heart valve prostheses: data from the German Aortic Valve Registry (GARY).</h4><i>Rudolph TK, Herrmann E, Bon D, Walther T, ... Rudolph V, Bleiziffer S</i><br /><b>Background</b><br />Various second-generation transcatheter heart valve (THV) prostheses with high clinical efficacy and safety are available, but there is limited large-scale data available comparing their hemodynamic performance and clinical implications.<br /><b>Objective</b><br />To compare the hemodynamic performance and short-term clinical outcome of four second-generation THV prostheses.<br /><b>Methods</b><br />24,124 patients out of the German Aortic Valve Registry who underwent transfemoral transcatheter aortic valve implantation (TAVI) (Evolut™ R n = 7028, Acurate neo™ n = 2922, Portico n = 878 and Sapien 3 n = 13,296) were included in this analysis. Propensity-score weighted analysis was performed to control for differences in age, left ventricular function, STS score and sex. Primary endpoint was survival at one-year, secondary endpoints were 30 days survival, pre-discharge transvalvular gradients, paravalvular leakage and peri-procedural complications.<br /><b>Results</b><br />Thirty-day and one-year survival were not significantly different between the four patient groups. Transvalvular gradients in Evolut™ R and Acurate neo™ were significantly lower as compared to Portico and Sapien 3 at hospital discharge. This difference exists across all annulus sizes. Paravalvular leakage ≥ II occurred significantly less often in the Sapien 3 group (1.2%, p < 0.0001). Rate of severe procedural complications was low and comparable in all groups. Permanent pacemaker implantation rate at one year was lowest in the ACUARATE neo group (13.0%) and highest in the Evolut™ R group (21.9%).<br /><b>Conclusion</b><br />Albeit comparable short-term clinical outcomes there are certain differences regarding hemodynamic performance and permanent pacemaker implantation rate between currently available THV prostheses which should be considered for individual prosthesis selection.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 18 Jul 2023; epub ahead of print</small></div>

<div><h4>Type of evidence supporting ACC/AHA and ESC clinical practice guidelines for acute coronary syndrome.</h4><i>Gonzalez-Del-Hoyo M, Mas-Llado C, Blaya-Peña L, Siquier-Padilla J, ... Peral V, Rossello X</i><br /><b>Aim</b><br />The aim of clinical practice guidelines for ST elevation myocardial infarction (STEMI) and non-ST elevation acute coronary syndrome (NSTE-ACS) is to assist healthcare professionals in clinical decision-making. We evaluated the type of studies supporting these guidelines and their recommendations.<br /><b>Methods</b><br />All references and recommendations in the 2013 and 2014 ACC/AHA and 2017 and 2020 (ESC clinical guidelines for STEMI and NSTE-ACS were reviewed. References were classified into meta-analyses, randomised, non-randomised, and other types (e.g., position papers, reviews). Recommendations were classified according to class and their level of evidence (LOE).<br /><b>Results</b><br />We retrieved 2128 non-duplicated references: 8.4% were meta-analyses, 26.2% randomised studies, 44.7% non-randomised studies, and 20.7% \'other\' papers. Meta-analyses were based on randomised data in 78% of cases and used individual-patient data in 20.2%. Compared to non-randomised studies, randomised studies were more frequently multicentre (85.5% vs. 65.5%) and international (58.2% vs. 28.5%). The type of studies supporting recommendations varied as per the LOE of the recommendation. For LOE-A recommendations, the breakdown of supporting recommendations was: 18.5% meta-analyses, 56.6% randomised studies, 16.6% non-randomised studies and 8.3% \'other\' papers; for LOE-B this breakdown was 9%, 39.8%, 38.2%, and 12.9%; and for LOE-C; 4.6%, 19.3%, 30.3%, and 45.9%.<br /><b>Conclusions</b><br />The references supporting the ACC/AHA and ESC guidelines on STEMI and NSTE-ACS consisted of non-randomised studies in ~ 45% of cases, with less than a third of the references consisting of meta-analyses and randomised studies. The type of studies supporting guideline recommendations varied widely by the LOE of the recommendation.<br /><br />© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.<br /><br /><small>Clin Res Cardiol: 12 Jul 2023; epub ahead of print</small></div>

<div><h4>Five-year-outcome of new-onset perioperative atrial fibrillation after left atrial appendage amputation concomitant with cardiac surgery.</h4><i>Gerçek M, Börgermann J, Gummert J, Gerçek M</i><br /><b>Background</b><br />Recent data demonstrated the benefit of left atrial appendage (LAA)-amputation in patients with atrial fibrillation (AF). However, the long-term impact of LAA-amputation for patients with new-onset perioperative atrial fibrillation (POAF) is still unknown.<br /><b>Methods</b><br />Patients with no history of AF undergoing coronary artery bypass grafting by off-pump technique (OPCAB) between 2014 and 2016 were retrospectively examined. Cohorts were divided by the concomitant execution of LAA-amputation. Propensity score (PS) matching was applied by all available baseline characteristics. The composite of all-cause mortality, stroke and rehospitalization in patients with POAF and patients maintaining sinus rhythm posed as the primary endpoint.<br /><b>Results</b><br />A total of 1522 patients were enrolled, of whom 1208 and 243 were included in the control and the LAA-amputation group, respectively and were matched to 243 patients in each group. In total, patients with POAF without LAA-amputation showed a significantly higher rate of the composite endpoint (17.3% vs 32.1%, p = 0.007). However, patients with LAA-amputation showed no significant difference in the composite endpoint (23.2% vs 26.7%, p = 0.57). The significantly higher occurrence of the composite endpoint was driven by all-cause mortality (p = 0.005) and rehospitalization (p = 0.029). Subgroup analysis revealed a CHA<sub>2</sub>DS<sub>2</sub>-VASc-score of ≥ 3 to be associated with the high rate of the primary endpoint (p = 0.004).<br /><b>Conclusion</b><br />POAF is associated with a higher rate of the combined endpoint of all-cause mortality, stroke and rehospitalization. The composite endpoint in patients with LAA-amputation concomitant with OPCAB surgery developing new-onset POAF in a 5-year follow-up was not increased compared to a control cohort maintaining sinus rhythm. Five-year outcome of patients with POAF and LAA-amputation; 95% CI, 95% confidence interval, CPR, cardiopulmonary resuscitation, ECLS, extracorporeal life support, HR, hazard ratio, IABP, intra-aortic balloon pump, LAA, left atrial appendage, OPCAB, off-pump coronary artery bypass grafting, PAPs, systolic pulmonary artery pressure, SR, sinus rhythm, VT, ventricular tachycardia.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 10 Jul 2023; epub ahead of print</small></div>

<div><h4>High interindividual variability in LDL-cholesterol reductions after inclisiran administration in a real-world multicenter setting in Germany.</h4><i>Makhmudova U, Schatz U, Perakakis N, Kassner U, ... Weingärtner O, German Inclisiran Network (GIN)</i><br /><b>Background:</b><br/>and aims</b><br />Low-density lipoprotein cholesterol (LDL-C) is the main therapeutic target in the treatment of hypercholesterolemia. Small interfering RNA (siRNA) inclisiran is a new drug, which targets PCSK9 mRNA in the liver, reducing concentrations of circulating LDL-C. In randomized trials, inclisiran demonstrated a substantial reduction in LDL-C. The German Inclisiran Network (GIN) aims to evaluate LDL-C reductions in a real-world cohort of patients treated with inclisiran in Germany.<br /><b>Methods</b><br />Patients who received inclisiran in 14 lipid clinics in Germany for elevated LDL-C levels between February 2021 and July 2022 were included in this analysis. We described baseline characteristics, individual LDL-C changes (%) and side effects in 153 patients 3 months (n = 153) and 9 months (n = 79) after inclisiran administration.<br /><b>Results</b><br />Since all patients were referred to specialized lipid clinics, only one-third were on statin therapy due to statin intolerance. The median LDL-C reduction was 35.5% at 3 months and 26.5% at 9 months. In patients previously treated with PCSK9 antibody (PCSK9-mAb), LDL-C reductions were less effective than in PCSK9-mAb-naïve patients (23.6% vs. 41.1% at 3 months). Concomitant statin treatment was associated with more effective LDL-C lowering. There was a high interindividual variability in LDL-C changes from baseline. Altogether, inclisiran was well-tolerated, and side effects were rare (5.9%).<br /><b>Conclusion</b><br />In this real-world patient population referred to German lipid clinics for elevated LDL-C levels, inclisiran demonstrated a high interindividual variability in LDL-C reductions. Further research is warranted to elucidate reasons for the interindividual variability in drug efficacy.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 09 Jul 2023; epub ahead of print</small></div>

<div><h4>Heart rate variability: reference values and role for clinical profile and mortality in individuals with heart failure.</h4><i>Zeid S, Buch G, Velmeden D, Söhne J, ... Prochaska JH, Wild PS</i><br /><b>Aims</b><br />To establish reference values and clinically relevant determinants for measures of heart rate variability (HRV) and to assess their relevance for clinical outcome prediction in individuals with heart failure.<br /><b>Methods</b><br />Data from the MyoVasc study (NCT04064450; N = 3289), a prospective cohort on chronic heart failure with a highly standardized, 5 h examination, and Holter ECG recording were investigated. HRV markers were selected using a systematic literature screen and a data-driven approach. Reference values were determined from a healthy subsample. Clinical determinants of HRV were investigated via multivariable linear regression analyses, while their relationship with mortality was investigated by multivariable Cox regression analyses.<br /><b>Results</b><br />Holter ECG recordings were available for analysis in 1001 study participants (mean age 64.5 ± 10.5 years; female sex 35.4%). While the most frequently reported HRV markers in literature were from time and frequency domains, the data-driven approach revealed predominantly non-linear HRV measures. Age, sex, dyslipidemia, family history of myocardial infarction or stroke, peripheral artery disease, and heart failure were strongly related to HRV in multivariable models. In a follow-up period of 6.5 years, acceleration capacity [HR<sub>perSD</sub> 1.53 (95% CI 1.21/1.93), p = 0.0004], deceleration capacity [HR<sub>perSD</sub>: 0.70 (95% CI 0.55/0.88), p = 0.002], and time lag [HR<sub>perSD</sub> 1.22 (95% CI 1.03/1.44), p = 0.018] were the strongest predictors of all-cause mortality in individuals with heart failure independently of cardiovascular risk factors, comorbidities, and medication.<br /><b>Conclusion</b><br />HRV markers are associated with the cardiovascular clinical profile and are strong and independent predictors of survival in heart failure. This underscores clinical relevance and interventional potential for individuals with heart failure.<br /><b>Gov identifier</b><br />NCT04064450.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 09 Jul 2023; epub ahead of print</small></div>

<div><h4>GRACE scores or high-sensitivity troponin for timing of coronary angiography in non-ST-elevation acute coronary syndromes.</h4><i>Jobs A, Boeddinghaus J, Neumann JT, Goßling A, ... Westermann D, Thiele H</i><br /><b>Background</b><br />The GRACE risk score is generically recommended by guidelines for timing of invasive coronary angiography without stating which score should be used. The aim was to determine the diagnostic performance of different GRACE risk scores in comparison to the ESC 0/1 h-algorithm using high-sensitivity cardiac troponin (hs-cTn).<br /><b>Methods</b><br />Prospectively enrolled patients presenting with symptoms suggestive of myocardial infarction (MI) in two large studies testing biomarker diagnostic strategies were included. Five GRACE risk scores were calculated. The amount of risk reclassification and the theoretical impact on guideline-recommended timing of invasive coronary angiography was studied.<br /><b>Results</b><br />Overall, 8,618 patients were eligible for analyses. Comparing different GRACE risk scores, up to 63.8% of participants were reclassified into a different risk category. The proportion of MIs identified (i.e., sensitivity) dramatically differed between GRACE risk scores (range 23.8-66.5%) and was lower for any score than for the ESC 0/1 h-algorithm (78.1%). Supplementing the ESC 0/1 h-algorithm with a GRACE risk score slightly increased sensitivity (P < 0.001 for all scores). However, this increased the number of false positive results.<br /><b>Conclusion</b><br />The substantial amount of risk reclassification causes clinically meaningful differences in the proportion of patients meeting the recommended threshold for pursuing early invasive strategy according to the different GRACE scores. The single best test to detect MIs is the ESC 0/1 h-algorithm. Combining GRACE risk scoring with hs-cTn testing slightly increases the detection of MIs but also increases the number of patients with false positive results who would undergo potential unnecessarily early invasive coronary angiography.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 08 Jul 2023; epub ahead of print</small></div>

<div><h4>Blood pressure changes during tenofovir-based antiretroviral therapy among people living with HIV in Lilongwe, Malawi: results from the prospective LighTen Cohort Study.</h4><i>Steffen HM, Mahanani MR, Neuhann F, Nhlema A, ... Winkler V, Phiri S</i><br /><b>Background</b><br />Sub-Saharan Africa is one of the regions in the world with the highest numbers of uncontrolled hypertension as well as people living with HIV/AIDS (PLHIV). However, the association between hypertension and antiretroviral therapy is controversial.<br /><b>Methods</b><br />Participant demographics, medical history, laboratory values, WHO clinical stage, current medication, and anthropometric data were recorded at study entry and during study visits at 1, 3, 6 months, and every 6 months thereafter until month 36. Patients who stopped or changed their antiretroviral therapy (tenofovir, lamivudine, efavirenz) were censored on that day. Office blood pressure (BP) was categorized using ≥ 2 measurements on ≥ 2 occasions during the first three visits. Factors associated with systolic and mean BP were analyzed using bivariable and multivariable multilevel linear regression.<br /><b>Results</b><br />1,288 PLHIV (751 females, 58.3%) could be included and 832 completed the 36 months of observation. Weight gain and a higher BP level at study entry were associated with an increase in BP (p < 0.001), while female sex (p < 0.001), lower body weight at study entry (p < 0.001), and high glomerular filtration rate (p = 0.009) protected against a rise in BP. The rate of uncontrolled BP remained high (73.9% vs. 72.1%) and despite indication treatment, adjustments were realized in a minority of cases (13%).<br /><b>Conclusion</b><br />Adherence to antihypertensive treatment and weight control should be addressed in patient education programs at centers caring for PLHIV in low-resources settings like Malawi. Together with intensified training of medical staff to overcome provider inertia, improved control rates of hypertension might eventually be achieved.<br /><b>Trial registration</b><br />NCT02381275.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 06 Jul 2023; epub ahead of print</small></div>

<div><h4>Non-Alcoholic Fatty Liver Disease (NAFLD) and risk of new-onset heart failure: a retrospective analysis of 173,966 patients.</h4><i>Roderburg C, Krieg S, Krieg A, Vaghiri S, ... Kostev K, Loosen SH</i><br /><b>Background</b><br />Non-alcoholic fatty liver disease (NAFLD) represents the leading cause of chronic liver disease. Its high mortality and morbidity are mainly caused by non-hepatic comorbidities and their clinical complications. Accumulating evidence suggests an association between NAFLD and heart failure (HF), but large-scale data analyses from Germany are scarce.<br /><b>Methods</b><br />Using the Disease Analyzer database (IQVIA), this analysis retrospectively evaluated two cohorts of outpatients with and without NAFLD with respect to the cumulative incidence of HF as the primary outcome between January 2005 and December 2020. Cohorts were propensity score matched for sex, age, index year, yearly consultation frequency, and known risk factors for HF.<br /><b>Results</b><br />A total of 173,966 patients were included in the analysis. Within 10 years of the index date, 13.2% vs. 10.0% of patients with and without NAFLD were newly diagnosed with HF (p < 0.001). This finding was supported by univariate Cox regression analysis in which NAFLD was found to be significantly associated with subsequent HF (Hazard Ratio (HR) 1.34, 95% Confidence Interval (CI) 1.28-1.39, p < 0.001). The association between NAFLD and HF was observed across all analysed age groups and as comparable between both men (HR 1.30, 95% CI 1.23-1.38; p < 0.001) and women (HR: 1.37, 95% CI 1.29-1.45; p < 0.001).<br /><b>Conclusion</b><br />NAFLD is significantly associated with an increased cumulative incidence of HF, which, given its rapidly increasing global prevalence, could be crucial to further reduce its high mortality and morbidity. We recommend risk stratification within a multidisciplinary approach for NAFLD patients, including systematic prevention or early detection strategies for HF.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 06 Jul 2023; epub ahead of print</small></div>

<div><h4>TRI-SCORE is superior to EuroSCORE II and STS-Score in mortality prediction following transcatheter edge-to-edge tricuspid valve repair.</h4><i>Gröger M, Friedl S, Ouerghemmi D, Tadic M, ... Markovic S, Keßler M</i><br /><b>Background</b><br />The development of transcatheter tricuspid edge-to-edge repair for tricuspid regurgitation is a therapeutic milestone but a specific periprocedural risk assessment tool is lacking. TRI-SCORE has recently been introduced as a dedicated risk score for tricuspid valve surgery.<br /><b>Aims</b><br />This study analyzes the predictive performance of TRI-SCORE following transcatheter edge-to-edge tricuspid valve repair.<br /><b>Methods</b><br />180 patients who underwent transcatheter tricuspid valve repair at Ulm University Hospital were consecutively included and stratified into three TRI-SCORE risk groups. The predictive performance of TRI-SCORE was assessed throughout a follow-up period of 30 days and up to 1 year.<br /><b>Results</b><br />All patients had severe tricuspid regurgitation. Median EuroSCORE II was 6.4% (IQR 3.8-10.1%), median STS-Score 8.1% (IQR 4.6-13.4%) and median TRI-SCORE 6.0 (IQR 4.0-7.0). 64 patients (35.6%) were in the low TRI-SCORE group, 91 (50.6%) in the intermediate and 25 (13.9%) in the high-risk groups. The procedural success rate was 97.8%. 30-day mortality was 0% in the low-risk group, 1.3% in the intermediate-risk and 17.4% in the high-risk groups (p < 0.001). During a median follow-up of 168 days mortality was 0%, 3.8% and 52.2%, respectively (p < 0.001). The predictive performance of TRI-SCORE was excellent (AUC for 30-day mortality: 90.3%, for one-year mortality: 93.1%) and superior to EuroSCORE II (AUC 56.6% and 64.4%, respectively) and STS-Score (AUC 61.0% and 59.0%, respectively).<br /><b>Conclusion</b><br />TRI-SCORE is a valuable tool for prediction of mortality after transcatheter edge-to-edge tricuspid valve repair and its performance is superior to EuroSCORE II and STS-Score. In a monocentric cohort of 180 patients undergoing edge-to-edge tricuspid valve repair TRI-SCORE predicted 30-day and up to one-year mortality more reliably than EuroSCORE II and STS-Score. AUC area under the curve, 95% CI 95% confidence interval.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 05 Jul 2023; epub ahead of print</small></div>

<div><h4>Initial therapeutic anticoagulation with rivaroxaban compared to prophylactic therapy with heparins in moderate to severe COVID-19: results of the COVID-PREVENT randomized controlled trial.</h4><i>Rauch-Kröhnert U, Puccini M, Placzek M, Beyer-Westendorf J, ... Anker SD, Landmesser U</i><br /><b>Background</b><br />COVID-19 is associated with a prothrombotic state. Current guidelines recommend prophylactic anticoagulation upon hospitalization.<br /><b>Methods</b><br />COVID-PREVENT, an open-label, multicenter, randomized, clinical trial enrolled patients (≥ 18 years) with moderate to severe COVID-19 and age-adjusted D-dimers > 1.5 upper limit of normal (ULN). The participants were randomly assigned (1:1) to receive either therapeutic anticoagulation with rivaroxaban 20 mg once daily or thromboprophylaxis with a heparin (SOC) for at least 7 days followed by prophylactic anticoagulation with rivaroxaban 10 mg once daily for 28 days or no thromboprophylaxis. The primary efficacy outcome was the D-dimer level and the co-primary efficacy outcome the 7-category ordinal COVID-19 scale by WHO at 7 days post randomization. The secondary outcome was time to the composite event of either venous or arterial thromboembolism, new myocardial infarction, non-hemorrhagic stroke, all-cause death or progression to intubation and invasive ventilation up to 35 days post randomization.<br /><b>Results</b><br />The primary efficacy outcome D-dimer at 7 days was not different between patients assigned to therapeutic (n = 55) or prophylactic anticoagulation (n = 56) (1.21 mg/L [0.79, 1.86] vs 1.27 mg/L [0.79, 2.04], p = 0.78). In the whole study population D-dimer was significantly lower at 7 days compared to baseline (1.05 mg/L [0.75, 1.48] vs 1.57 mg/L [1.13, 2.19], p < 0.0001). Therapy with rivaroxaban compared to SOC was not associated an improvement on the WHO 7-category ordinal scale at 7 days (p = 0.085). Rivaroxaban improved the clinical outcome measured by the score in patients with a higher baseline D-dimer  > 2.0 ULN (exploratory analysis; 0.632 [0.516, 0.748], p = 0.026). The secondary endpoint occurred in 6 patients (10.9%) in the rivaroxaban group and in 12 (21.4%) in the SOC group (time-to-first occurrence of the components of the secondary outcome: HR 0.5; 95% CI 0.15-1.67; p = 0.264). There was no difference in fatal or non-fatal major or clinically relevant non-major bleeding between the groups.<br /><b>Conclusions</b><br />Therapeutic anticoagulation with rivaroxaban compared to prophylactic anticoagulation with a heparin did not improve surrogates of clinical outcome in patients with moderate to severe COVID-19. Whether initial rivaroxaban at therapeutic doses might be superior to thromboprophylaxis in patients with COVID-19 and a high risk as defined by D-dimer  > 2 ULN needs confirmation in further studies.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 05 Jul 2023; epub ahead of print</small></div>

<div><h4>Prevalence and prognostic impact of chronic kidney disease and anaemia across ACC/AHA precursor and symptomatic heart failure stages.</h4><i>Gerhardt LMS, Kordsmeyer M, Sehner S, Güder G, ... Wanner C, Angermann CE</i><br /><b>Background</b><br />The importance of chronic kidney disease (CKD) and anaemia has not been comprehensively studied in asymptomatic patients at risk for heart failure (HF) versus those with symptomatic HF. We analysed the prevalence, characteristics and prognostic impact of both conditions across American College of Cardiology/American Heart Association (ACC/AHA) precursor and HF stages A-D.<br /><b>Methods and results</b><br />2496 participants from three non-pharmacological German Competence Network HF studies were categorized by ACC/AHA stage; stage C patients were subdivided into C1 and C2 (corresponding to NYHA classes I/II and III, respectively). Overall, patient distribution was 8.1%/35.3%/32.9% and 23.7% in ACC/AHA stages A/B/C1 and C2/D, respectively. These subgroups were stratified by the absence ( - ) or presence ( +) of CKD (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73m<sup>2</sup>) and anaemia (haemoglobin in women/men < 12/ < 13 g/dL). The primary outcome was all-cause mortality at 5-year follow-up. Prevalence increased across stages A/B/C1 and C2/D (CKD: 22.3%/23.6%/31.6%/54.7%; anaemia: 3.0%/7.9%/21.7%/33.2%, respectively), with concordant decreases in median eGFR and haemoglobin (all p < 0.001). Across all stages, hazard ratios [95% confidence intervals] for all-cause mortality were 2.1 [1.8-2.6] for CKD + , 1.7 [1.4-2.0] for anaemia, and 3.6 [2.9-4.6] for CKD + /anaemia + (all p < 0.001). Population attributable fractions (PAFs) for 5-year mortality related to CKD and/or anaemia were similar across stages A/B, C1 and C2/D (up to 33.4%, 30.8% and 34.7%, respectively).<br /><b>Conclusions</b><br />Prevalence and severity of CKD and anaemia increased across ACC/AHA stages. Both conditions were individually and additively associated with increased 5-year mortality risk, with similar PAFs in asymptomatic patients and those with symptomatic HF.<br /><br />© 2022. The Author(s).<br /><br /><small>Clin Res Cardiol: 01 Jul 2023; 112:868-879</small></div>

<div><h4>Effects of empagliflozin on left ventricular diastolic function in addition to usual care in individuals with type 2 diabetes mellitus-results from the randomized, double-blind, placebo-controlled EmDia trial.</h4><i>Prochaska JH, Jünger C, Schulz A, Arnold N, ... Münzel T, Wild PS</i><br /><b>Background</b><br />The sodium-glucose co-transporter 2 inhibitor empagliflozin improves cardiovascular outcome in patients with type 2 diabetes mellitus (T2DM) and heart failure. Experimental studies suggest a direct cardiac effect of empagliflozin associated with an improvement in left ventricular diastolic function.<br /><b>Methods</b><br />In the randomized, double-blind, two-armed, placebo-controlled, parallel group trial EmDia, patients with T2DM and elevated left ventricular E/E´ ratio were enrolled and randomized 1:1 to receive empagliflozin 10 mg/day versus placebo. The primary endpoint was the change of left ventricular E/E´ ratio after 12 weeks of intervention.<br /><b>Results</b><br />A total of 144 patients with T2DM and an elevated left ventricular E/e´ ratio (age 68.9 ± 7.7 years; 14.1% women; E/e´ ratio 9.61[8.24/11.14], left ventricular ejection fraction 58.9% ± 5.6%). After 12 weeks of intervention, empagliflozin resulted in a significant higher decrease in the primary endpoint E/e´ ratio by - 1.18 ([95% confidence interval (CI) - 1.72/- 0.65]; P < 0.0001) compared with placebo. The beneficial effect of empagliflozin was consistent across all subgroups and also occurred in subjects with heart failure and preserved ejection fraction (n = 30). Additional effects of empagliflozin on body weight, HbA1c, uric acid, red blood cell count, hemoglobin, mean corpuscular hemoglobin, and hematocrit were detected (all P < 0.001). Approximately one-third of the reduction in E/e´ by empagliflozin could be explained by the variables examined.<br /><b>Conclusions</b><br />Empagliflozin improves diastolic function in patients with T2DM and elevated end-diastolic pressure. Since the positive effects were consistent in patients with and without heart failure with preserved ejection fraction, the data add a mechanistic insight for the beneficial cardiovascular effect of empagliflozin.<br /><b>Trial registration</b><br />Clinicaltrials.gov, unique identifier: NCT02932436.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 01 Jul 2023; 112:911-922</small></div>

<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: 01 Jul 2023; 112:855-867</small></div>

<div><h4>Long-term outcomes following transcatheter aortic valve implantation with the Portico self-expanding valve.</h4><i>Giordano A, Mas-Peiro S, Fichtlscherer S, Schaefer A, ... Corcione N, Biondi-Zoccai G</i><br /><b>Aim</b><br />Transcatheter aortic valve implantation (TAVI) is a mainstay in the management of severe aortic valve stenosis in elderly patients, but there is uncertainty on their long-term effectiveness. We aimed to assess the long-term outcome of patients undergoing TAVI with the Portico valve.<br /><b>Methods</b><br />We retrospectively collected the data on patients in whom TAVI with Portico was attempted from 7 high-volume centres. Only patients theoretically eligible for 3 or more years of follow-up were included. Clinical outcomes, including death, stroke, myocardial infarction, reintervention for valve degeneration and hemodynamic valve performance were systematically assessed.<br /><b>Results</b><br />A total of 803 patients were included, with 504 (62.8%) women, mean age of 82 years, median EuroSCORE II of 3.1%, and 386 (48.1%) subjects at low/moderate risk. The median follow-up was 3.0 years (3.0; 4.0). The composite of death, stroke, myocardial infarction, and reintervention for valve degeneration occurred in 37.5% (95% confidence interval: 34.1-40.9%), with all-cause death in 35.1% (31.8-38.4%), stroke in 3.4% (1.3-3.4%), myocardial infarction in 1.0% (0.3-1.5%), and reintervention for valve degeneration in 1.1% (0.6-2.1%). The mean aortic valve gradient at follow-up was 8.1 ± 4.6 mmHg, and at least moderate aortic regurgitation was present in 9.1% (6.7-12.3%). Independent predictors of major adverse events or death were: peripheral artery disease, chronic obstructive pulmonary disease, estimated glomerular filtration rate, atrial fibrillation, prior pacemaker implantation, EuroSCORE II, and reduced left ventricular ejection fraction (all p < 0.05).<br /><b>Conclusions</b><br />Portico use is associated with favorable long-term clinical outcomes. Clinical outcomes were largely impacted by baseline risk factors and surgical risk.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 30 Jun 2023; epub ahead of print</small></div>

<div><h4>Role of dietary sodium restriction in chronic heart failure: systematic review and meta-analysis.</h4><i>Urban S, Fułek M, Błaziak M, Fułek K, ... Ponikowski P, Biegus J</i><br /><b>Background</b><br />Dietary sodium restriction remains a guidelines-approved lifestyle recommendation for chronic heart failure (CHF) patients. However, its efficacy in clinical outcome improvement is dubious.<br /><b>Objective</b><br />The study evaluated whether dietary sodium restriction in CHF reduces clinical events.<br /><b>Methods</b><br />We performed a systematic review of the following databases: Academic Search Ultimate, ERIC, Health Source Nursing/Academic Edition, MEDLINE, Embase, Clinicaltrials.gov and Cochrane Library (trials) to find studies analysing the impact of sodium restriction in the adult CHF population. Both observational and interventional studies were included. Exclusion criteria included i.e.: sodium consumption assessment based only on natriuresis, in-hospital interventions or mixed interventions-e.g. sodium and fluid restriction in one arm only. The review was conducted following PRISMA guidelines. Meta-analysis was performed for the endpoints reported in at least 3 papers. Analyses were conducted in Review Manager (RevMan) Version 5.4.1.<br /><b>Results</b><br />Initially, we screened 9175 articles. Backward snowballing revealed 1050 additional articles. Eventually, 9 papers were evaluated in the meta-analysis. All-cause mortality, HF-related hospitalizations and the composite of mortality and hospitalisation were reported in 8, 6 and 3 articles, respectively. Sodium restriction was associated with a higher risk of the composite endpoint (OR 4.12 [95% CI 1.23-13.82]) and did not significantly affect the all-cause mortality (OR 1.38 [95% CI 0.76-2.49]) or HF hospitalisation (OR 1.63 [95% CI 0.69-3.88]).<br /><b>Conclusions</b><br />In a meta-analysis, sodium restriction in CHF patients worsened the prognosis in terms of a composite of mortality and hospitalizations and did not influence all-cause mortality and HF hospitalisation rate.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 30 Jun 2023; epub ahead of print</small></div>

<div><h4>Vaccine-carditis study: Spanish multicenter registry of inflammatory heart disease after COVID-19 vaccination.</h4><i>Pastor Pueyo P, Gambó Ruberte E, Gayán Ordás J, Matute Blanco L, ... Soriano Colomé T, Worner Diz F</i><br /><b>Introduction:</b><br/>and objectives</b><br />Vaccines against SARS-CoV-2 have been a major scientific and medical achievement in the control of the COVID-19 pandemic. However, very infrequent cases of inflammatory heart disease have been described as adverse events, leading to uncertainty in the scientific community and in the general population.<br /><b>Methods</b><br />The Vaccine-Carditis Registry has included all cases of myocarditis and pericarditis diagnosed within 30 days after COVID-19 vaccination since August 1, 2021 in 29 centers throughout the Spanish territory. The definitions of myocarditis (probable or confirmed) and pericarditis followed the consensus of the Centers for Disease Control and the Clinical Practice Guidelines of the European Society of Cardiology. A comprehensive analysis of clinical characteristics and 3-month evolution is presented.<br /><b>Results</b><br />From August 1, 2021, to March 10, 2022, 139 cases of myocarditis or pericarditis were recorded (81.3% male, median age 28 years). Most cases were detected in the 1st week after administration of an mRNA vaccine, the majority after the second dose. The most common presentation was mixed inflammatory disease (myocarditis and pericarditis). 11% had left ventricular systolic dysfunction, 4% had right ventricular systolic dysfunction, and 21% had pericardial effusion. In cardiac magnetic resonance studies, left ventricular inferolateral involvement was the most frequent pattern (58%). More than 90% of cases had a benign clinical course. After a 3-month follow-up, the incidence of adverse events was 12.78% (1.44% mortality).<br /><b>Conclusions</b><br />In our setting, inflammatory heart disease after vaccination against SARS-CoV-2 predominantly affects young men in the 1st week after the second dose of RNA-m vaccine and presents a favorable clinical course in most cases.<br /><br />© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.<br /><br /><small>Clin Res Cardiol: 27 Jun 2023; epub ahead of print</small></div>