Journal: Clin Res Cardiol

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Abstract

SARS-CoV-2, myocardial injury and inflammation: insights from a large clinical and autopsy study.

Dal Ferro M, Bussani R, Paldino A, Nuzzi V, ... Merlo M, Sinagra G
Objective
Despite growing evidence about myocardial injury in hospitalized COronaVIrus Disease 2019 (COVID-19) patients, the mechanism behind this injury is only poorly understood and little is known about its association with SARS-CoV-2-mediated myocarditis. Furthermore, definite evidence of the presence and role of SARS-CoV-2 in cardiomyocytes in the clinical scenario is still lacking.
Methods
We histologically characterized myocardial tissue of 40 patients deceased with severe SARS-CoV-2 infection during the first wave of the pandemic. Clinical data were also recorded and analyzed. In case of findings supportive of myocardial inflammation, histological analysis was complemented by RT-PCR and immunohistochemistry for SARS-CoV-2 viral antigens and in situ RNA hybridization for the detection of viral genomes.
Results
Both chronic and acute myocardial damage was invariably present, correlating with the age and comorbidities of our population. Myocarditis of overt entity was found in one case (2.5%). SARS-CoV-2 genome was not found in the cardiomyocytes of the patient with myocarditis, while it was focally and negligibly present in cardiomyocytes of patients with known viral persistence in the lungs and no signs of myocardial inflammation. The presence of myocardial injury was not associated with myocardial inflammatory infiltrates.
Conclusions
In this autopsy cohort of COVID-19 patients, myocarditis is rarely found and not associated with SARS-CoV-2 presence in cardiomyocytes. Chronic and acute forms of myocardial damage are constantly found and correlate with the severity of COVID-19 disease and pre-existing comorbidities.

© 2021. The Author(s).

Clin Res Cardiol: 18 Jul 2021; epub ahead of print
Dal Ferro M, Bussani R, Paldino A, Nuzzi V, ... Merlo M, Sinagra G
Clin Res Cardiol: 18 Jul 2021; epub ahead of print | PMID: 34282465
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Abstract

Feasibility and effectiveness of a multidimensional post-discharge disease management programme for heart failure patients in clinical practice: the HerzMobil Tirol programme.

Poelzl G, Egelseer-Bruendl T, Pfeifer B, Modre-Osprian R, ... Ammenwerth E, Bauer A
Aims
It remains unclear whether transitional care management outside of a clinical trial setting provides benefits for patients with acute heart failure (AHF) after hospitalization. We evaluated the feasibility and effectiveness of a multidimensional post-discharge disease management programme using a telemedical monitoring system incorporated in a comprehensive network of heart failure nurses, resident physicians, and secondary and tertiary referral centres (HerzMobil Tirol, HMT), METHODS AND
Results:
The non-randomized study included 508 AHF patients that were managed in HMT (n = 251) or contemporaneously in usual care (UC, n = 257) after discharge from hospital from 2016 to 2019. Groups were retrospectively matched for age and sex. The primary endpoint was time to HF readmission and all-cause mortality within 6 months. Multivariable Cox proportional hazard models were used to assess the effectiveness. The primary endpoint occurred in 48 patients (19.1%) in HMT and 89 (34.6%) in UC. Compared with UC, management by HMT was associated with a 46%-reduction in the primary endpoint (adjusted HR 0.54; 95% CI 0.37-0.77; P < 0.001). Subgroup analyses revealed consistent effectiveness. The composite of recurrent HF hospitalization and death within 6 months per 100 patient-years was 64.2 in HMT and 108.2 in UC (adjusted HR 0.41; 95% CI 0.29-0.55; P < 0.001 with death considered as a competing risk). After 1 year, 25 (10%) patients died in HMT compared with 66 (25.7%) in UC (HR 0.38; 95% CI 0.23-0.61, P < 0.001).
Conclusions
A multidimensional post-discharge disease management programme, comprising a telemedical monitoring system incorporated in a comprehensive network of specialized heart failure nurses and resident physicians, is feasible and effective in clinical practice.

© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.

Clin Res Cardiol: 15 Jul 2021; epub ahead of print
Poelzl G, Egelseer-Bruendl T, Pfeifer B, Modre-Osprian R, ... Ammenwerth E, Bauer A
Clin Res Cardiol: 15 Jul 2021; epub ahead of print | PMID: 34269863
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Abstract

Diastolic dysfunction in individuals with and without heart failure with preserved ejection fraction.

Wenzel JP, Kellen RB, Magnussen C, Blankenberg S, ... Schnabel R, Nikorowitsch J
Aim
Left ventricular diastolic dysfunction (DD), a common finding in the general population, is considered to be associated with heart failure with preserved ejection faction (HFpEF). Here we evaluate the prevalence and correlates of DD in subjects with and without HFpEF in a middle-aged sample of the general population.
Methods and results
From the first 10,000 participants of the population-based Hamburg City Health Study (HCHS), 5913 subjects (mean age 64.4 ± 8.3 years, 51.3% females), qualified for the current analysis. Diastolic dysfunction (DD) was identified in 753 (12.7%) participants. Of those, 11.2% showed DD without HFpEF (ALVDD) while 1.3% suffered from DD with HFpEF (DDwHFpEF). In multivariable regression analysis adjusted for major cardiovascular risk factors, ALVDD was associated with arterial hypertension (OR 2.0, p < 0.001) and HbA1c (OR 1.2, p = 0.007). Associations of both ALVDD and DDwHFpEF were: age (OR 1.7, p < 0.001; OR 2.7, p < 0.001), BMI (OR 1.2, p < 0.001; OR 1.6, p = 0.001), and left ventricular mass index (LVMI). In contrast, female sex (OR 2.5, p = 0.006), atrial fibrillation (OR 2.6, p = 0.024), CAD (OR 7.2, p < 0.001) COPD (OR 3.9, p < 0.001), and QRS duration (OR 1.4, p = 0.005) were strongly associated with DDwHFpEF but not with ALVDD.
Conclusion
The prevalence of DD in a sample from the first 10,000 participants of the population-based HCHS was 12.7% of whom 1.3% suffered from HFpEF. DD with and without HFpEF showed significant associations with different major cardiovascular risk factors and comorbidities warranting further research for their possible role in the formation of both ALVDD and DDwHFpEF.

© 2021. The Author(s).

Clin Res Cardiol: 15 Jul 2021; epub ahead of print
Wenzel JP, Kellen RB, Magnussen C, Blankenberg S, ... Schnabel R, Nikorowitsch J
Clin Res Cardiol: 15 Jul 2021; epub ahead of print | PMID: 34269862
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Abstract

Predicting survival in heart failure: a risk score based on machine-learning and change point algorithm.

Kim W, Park JJ, Lee HY, Kim KH, ... Kook W, Choi DJ
Objective
Machine learning (ML) algorithm can improve risk prediction because ML can select features and segment continuous variables effectively unbiased. We generated a risk score model for mortality with ML algorithms in East-Asian patients with heart failure (HF).
Methods
From the Korean Acute Heart Failure (KorAHF) registry, we used the data of 3683 patients with 27 continuous and 44 categorical variables. Grouped Lasso algorithm was used for the feature selection, and a novel continuous variable segmentation algorithm which is based on change-point analysis was developed for effectively segmenting the ranges of the continuous variables. Then, a risk score was assigned to each feature reflecting nonlinear relationship between features and survival times, and an integer score of maximum 100 was calculated for each patient.
Results
During 3-year follow-up time, 32.8% patients died. Using grouped Lasso, we identified 15 highly significant independent clinical features. The calculated risk score of each patient ranged between 1 and 71 points with a median of 36 (interquartile range: 27-45). The 3-year survival differed according to the quintiles of the risk score, being 80% and 17% in the 1st and 5th quintile, respectively. In addition, ML risk score had higher AUCs than MAGGIC-HF score to predict 1-year mortality (0.751 vs. 0.711, P < 0.001).
Conclusions
In East-Asian patients with HF, a novel risk score model based on ML and the new continuous variable segmentation algorithm performs better for mortality prediction than conventional prediction models.
Clinical trial registration
Unique identifier: INCT01389843 https://clinicaltrials.gov/ct2/show/NCT01389843 .

© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.

Clin Res Cardiol: 13 Jul 2021; epub ahead of print
Kim W, Park JJ, Lee HY, Kim KH, ... Kook W, Choi DJ
Clin Res Cardiol: 13 Jul 2021; epub ahead of print | PMID: 34259921
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Abstract

Feasibility and safety of minimal-contrast IVUS-guided rotational atherectomy for complex calcified coronary artery disease.

Allali A, Traboulsi H, Sulimov DS, Abdel-Wahab M, ... Toelg R, Richardt G
Objectives
To assess the feasibility and safety of minimal-contrast percutaneous coronary intervention (PCI) using rotational atherectomy (RA) in patients with severe coronary calcification at high-risk of contrast-associated acute kidney injury (AKI).
Methods
Twenty-six patients with advanced chronic kidney disease undergoing PCI with RA at three high-volume centres were included. Baseline intravascular ultrasound (IVUS) was performed to assess lesion morphology, and to guide burr-, balloon-, and stent-selection. Final result was assessed by IVUS and angiographically. Feasibility and safety were determined by procedural and in-hospital complications, and efficacy was assessed by freedom from contrast-associated AKI after PCI. Procedural and in-hospital outcome was compared to a propensity-matched population of standard RA PCI.
Results
Mean glomerular filtration rate was 32 ± 17 ml/min/1.73 m2. In seven cases PCI was performed in the setting of acute coronary syndrome. The left main coronary artery was treated in 27.8% and a two-stent bifurcation technique in 44.4%. RA was more often performed electively compared to the standard RA cohort (92.3 vs. 50%; p = 0.0016). Angiographic success was achieved in 100% and documented with a median contrast amount of 12.5 ml [Range 4-43]. No in-hospital death or myocardial infarction was reported. Contrast-associated AKI occurred in one patient versus five patients in standard RA group (p = 0.19). Shorter fluoroscopy time and lower radiation dose were achieved as compared to standard RA.
Conclusion
A minimal-contrast RA approach with IVUS-guidance for treatment of complex calcified coronary lesions is feasible and safe with high success rate.

© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.

Clin Res Cardiol: 12 Jul 2021; epub ahead of print
Allali A, Traboulsi H, Sulimov DS, Abdel-Wahab M, ... Toelg R, Richardt G
Clin Res Cardiol: 12 Jul 2021; epub ahead of print | PMID: 34255133
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Abstract

Quantitative flow ratio (QFR) identifies functional relevance of non-culprit lesions in coronary angiographies of patients with acute myocardial infarction.

Milzi A, Dettori R, Marx N, Reith S, Burgmaier M
Introduction
In patients with acute myocardial infarction (AMI) and multivessel coronary disease, revascularization of non-culprit lesions guided by proof of ischemia usually requires staged ischemia testing. Quantitative flow ratio (QFR) has been shown to be effective in assessing the hemodynamic relevance of lesions in stable coronary disease. However, its suitability in AMI patients is unknown. In this study, we tested the diagnostic value of QFR based on acute angiograms (aQFR) during AMI to assess the hemodynamic relevance of non-culprit lesions.
Methods
We retrospectively assessed the diagnostic efficiency of aQFR in 280 vessels from 220 patients, comparing it with staged ischemia testing using elective coronary angiography with FFR (n = 47), stress cardiac MRI (n = 200) or SPECT (n = 33).
Results
aQFR showed a very good diagnostic efficiency (AUC = 0.887, 95% CI 0.832-0.943, p < 0.001) in predicting ischemia of non-culprit lesions, significantly superior to coronary lesion\'s geometry as assessed by quantitative coronary angiography. The optimal cut-off for aQFR to predict ischemia was 0.80 (sensitivity = 83.7%, specificity = 86.1%). Maintaining a predefined level of 95% sensitivity and specificity, we created a decision model based on aQFR: lesions with aQFR ≤ 0.75 should be treated, lesions with aQFR ≥ 0.92 do not yield any hemodynamic relevance, and lesions in the \"grey zone\" (aQFR 0.75-0.92) benefit from further ischemia testings. This model would allow to reduce staged ischemia tests by 46.8% without a relevant loss in diagnostic efficiency.
Conclusion
Our data demonstrate that aQFR allows an effective assessment of hemodynamic relevance of non-culprit lesions in AMI and may guide interventions of non-culprit coronary lesions.

© 2021. The Author(s).

Clin Res Cardiol: 11 Jul 2021; epub ahead of print
Milzi A, Dettori R, Marx N, Reith S, Burgmaier M
Clin Res Cardiol: 11 Jul 2021; epub ahead of print | PMID: 34251507
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Abstract

Prognostic value of hepatorenal function following transcatheter edge-to-edge mitral valve repair.

Tanaka T, Kavsur R, Spieker M, Iliadis C, ... Westenfeld R, Becher MU
Background
Hepatorenal dysfunction is a strong prognostic predictor in patients with heart failure. However, the prognostic impact of the hepatorenal dysfunction in patients undergoing transcatheter mitral valve repair (TMVR) has not been well studied.
Methods
In consecutive patients who underwent edge-to-edge TMVR at three German centers, the model for end-stage liver disease excluding international normalized ratio (MELD-XI) score was calculated as 5.11 × ln [serum total bilirubin (mg/dl)] + 11.76 × ln [serum creatinine (mg/dl)] + 9.44. Patients were stratified into high (> 11) or low (≤ 11) MELD-XI score of which an incidence of the composite outcome, consisting of all-cause mortality and heart failure hospitalization, within 2 years after TMVR was assessed.
Results
Of the 881 patients, the mean MELD-XI score was 11.0 ± 5.9, and 415 patients (47.1%) had high MELD-XI score. The MELD-XI score was correlated with male, effective regurgitant orifice area, and tricuspid regurgitation severity and inversely related to left ventricular ejection fraction. Patients with high MELD-XI score had a higher incidence of the composite outcome than those with low MELD-XI score (47.7% vs. 29.8%; p < 0.0001), and in multivariable analysis, the high MELD-XI score was an independent predictor of the composite outcome [adjusted hazard ratio (HR) 1.34; 95% confidence interval (CI) 1.02-1.77; p = 0.04). Additionally, the MELD-XI score as a continuous variable was also an independent predictor (adjusted HR 1.02; 95% CI 1.00-1.05; p = 0.048).
Conclusions
The MELD-XI score was associated with clinical outcomes within 2 years after TMVR and can be a useful risk-stratification tool in patients undergoing TMVR.

© 2021. The Author(s).

Clin Res Cardiol: 11 Jul 2021; epub ahead of print
Tanaka T, Kavsur R, Spieker M, Iliadis C, ... Westenfeld R, Becher MU
Clin Res Cardiol: 11 Jul 2021; epub ahead of print | PMID: 34254179
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Abstract

Poor humoral and T-cell response to two-dose SARS-CoV-2 messenger RNA vaccine BNT162b2 in cardiothoracic transplant recipients.

Schramm R, Costard-Jäckle A, Rivinius R, Fischer B, ... Knabbe C, Gummert J
Aims
Immunocompromised patients have been excluded from studies of SARS-CoV-2 messenger RNA vaccines. The immune response to vaccines against other infectious agents has been shown to be blunted in such patients. We aimed to analyse the humoral and cellular response to prime-boost vaccination with the BNT162b2 vaccine (Pfizer-BioNTech) in cardiothoracic transplant recipients.
Methods and results
A total of 50 transplant patients [1-3 years post heart (42), lung (7), or heart-lung (1) transplant, mean age 55 ± 10 years] and a control group of 50 healthy staff members were included. Blood samples were analysed 21 days after the prime and the boosting dose, respectively, to quantify anti-SARS-CoV-2 spike protein (S) immunoglobulin titres (tested by Abbott, Euroimmun and RocheElecsys Immunoassays, each) and the functional inhibitory capacity of neutralizing antibodies (Genscript). To test for a specific T-cell response, heparinized whole blood was stimulated with SARS-CoV-2 specific peptides, covering domains of the viral spike, nucleocapsid and membrane protein, and the interferon-γ release was measured (QuantiFERON Monitor ELISA, Qiagen). The vast majority of transplant patients (90%) showed neither a detectable humoral nor a T-cell response three weeks after the completed two-dose BNT162b2 vaccination; these results are in sharp contrast to the robust immunogenicity seen in the control group: 98% exhibited seroconversion after the prime dose already, with a further significant increase of IgG titres after the booster dose (average > tenfold increase), a more than 90% inhibition capability of neutralizing antibodies as well as evidence of a T-cell responsiveness.
Conclusions
The findings of poor immune responses to a two-dose BNT162b2 vaccination in cardiothoracic transplant patients have a significant impact for organ transplant recipients specifically and possibly for immunocompromised patients in general. It urges for a review of future vaccine strategies in these patients.

© 2021. The Author(s).

Clin Res Cardiol: 08 Jul 2021; epub ahead of print
Schramm R, Costard-Jäckle A, Rivinius R, Fischer B, ... Knabbe C, Gummert J
Clin Res Cardiol: 08 Jul 2021; epub ahead of print | PMID: 34241676
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Abstract

Rationale and design of the EPCHF trial: the early palliative care in heart failure trial (EPCHF).

Becher MU, Balata M, Hesse M, Draht F, ... Radbruch L, Nickenig G
The progressive nature of heart failure (HF) coupled with high mortality and poor quality-of-life (QoL) mandates greater attention to palliative care (PC) as a routine component of HF management. Limited evidence exists from randomized controlled trials supporting the use of interdisciplinary palliative care in the progressive course of HF. The early palliative care in heart failure trial (EPCHF) is a prospective, controlled, nonblinded, multicenter study of an interdisciplinary palliative care intervention in 200 patients with symptomatic HF characterized by NYHA ≥ 2. The 12-month EPCHF intervention includes monthly consultations by a palliative care team focusing on physical and psychosocial symptom relief, attention to spiritual concerns and advance care planning. The primary endpoint is evaluated by health-related QoL questionnaires after 12 months of treatment. First the functional assessment of chronic illness therapy palliative care (FACIT-Pal) score evaluating QoL living with a chronic disease and second the Kansas City cardiomyopathy questionnaire (KCCQ) measuring QoL living with heart failure will be determined. Secondary endpoints are changes in anxiety/depression (HADS), symptom burden score (MIDOS), spiritual well-being functional assessment of chronic illness therapy spiritual well-being scale (FACIT-Sp), medical resource and cost assessment. EPCHF will help evaluate the efficacy and cost-effectiveness of palliative care in symptomatic HF using a patient-centered outcome as well as clinical and economic endpoints. EPCHF is funded by the Bundesministerium für Bildung und Forschung (BMBF, 01GY17).

© 2021. The Author(s).

Clin Res Cardiol: 08 Jul 2021; epub ahead of print
Becher MU, Balata M, Hesse M, Draht F, ... Radbruch L, Nickenig G
Clin Res Cardiol: 08 Jul 2021; epub ahead of print | PMID: 34241674
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Abstract

Prevalence and clinical characteristics of prediabetes and diabetes mellitus in young patients with ST-segment elevation myocardial infarction.

Mata Marín LA, Schmucker J, Fach A, Osteresch R, ... Hambrecht R, Wienbergen H
Background
Only few data on the prevalence of DM in young patients with ST-elevation myocardial infarction (STEMI) exist. Aim of the present study was to analyse this prevalence, its association to other cardiovascular risk factors and its impact on severity of CAD. In a substudy, consecutive HbA1c measurements in each patient were evaluated.
Methods
All patients ≤ 45 years old, admitted with STEMI to an overregional German Heart Centre and treated with primary coronary intervention between 2006 and 2019, entered analysis. Since 2015 HbA1c measurements were performed to detect unknown dysglycaemia.
Results
Out of 776 young patients of the total cohort, 88 patients (11.4%) had a DM, while 688 (88.6%) did not. Diabetics were more likely to be obese (BMI ≥ 30 kg/m2, OR 2.4, 95%CI 1.4-4.0, p < 0.01) and very obese (BMI ≥ 40 kg/m2, OR 5.1, 95%CI 2.1-12.2, p < 0.01). In diabetics, a higher likelihood of subacute STEMI (OR 2.2, 95% CI 1.1-4.5, p < 0.05) and more advanced CAD (OR 1.6, 95% CI 1.0-2.6, p < 0.05) compared to non-diabetics was observed. 208 patients were included in the substudy with HbA1c measurements. Out of those, 26 patients (12%) had known DM, while 17 patients (8%) had newly diagnosed DM and 49 patients (24%) preDM. The combined prevalence of any type of dysglycaemia was 44%.
Conclusion
DM in young patients with STEMI was associated with (severe) obesity, a higher likelihood of subacute STEMI and more advanced CAD compared to non-diabetics. Measurement of HbA1c in every consecutive STEMI-patient increased the rate of detected dysglycaemias more than three times higher than in general population.



Clin Res Cardiol: 02 Jul 2021; epub ahead of print
Mata Marín LA, Schmucker J, Fach A, Osteresch R, ... Hambrecht R, Wienbergen H
Clin Res Cardiol: 02 Jul 2021; epub ahead of print | PMID: 34216252
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Abstract

Hypertension control and end-stage renal disease in atrial fibrillation: a nationwide population-based cohort study.

Kwon S, Lee SR, Choi EK, Jung JH, ... Oh S, Lip GYH
Background
The impact of hypertension control on the risk of end-stage renal disease (ESRD) in patients newly diagnosed with atrial fibrillation (AF) is unknown. This study aimed to investigate the impact of hypertension control on incident ESRD among AF patients.
Methods
From the National Health Information database of Korea, we identified ESRD-free patients who were newly diagnosed with AF during 2010 and 2016. The patients were divided into four groups (NN, NH, HN, and HH) according to combinations of dichotomous blood pressure status [normotensive (N) or hypertensive (H)] of two consecutive check-ups. The primary outcome was incident ESRD. Cox proportional hazard regression analysis evaluated ESRD risks across the groups. The association between ESRD risks and changes in blood pressures was also evaluated.
Results
During the mean follow-up duration of 3.2 ± 1.9 years, 130,259 ESRD-free patients with AF (mean age 63.1 ± 12.1 years, male 61.2%) were evaluated. Compared to NN, other patient groups showed higher ESRD risks [hazard ratio (95% confidence interval) = 1.43 (1.08-1.89), 1.39 (1.08-1.79), and 2.03 (1.55-2.65) for NH, HN, and HH, respectively]. There was a significant trend of decreasing risks of ESRD in patients with greater reductions in systolic blood pressure after AF diagnosis (p for-trend < 0.001). The association between hypertension control and the ESRD risk was more accentuated in patients with chronic kidney disease.
Conclusion
Uncontrolled hypertension was associated with an increased risk of incident ESRD in patients with newly diagnosed AF. This study emphasizes the importance of blood pressure control once patients are diagnosed with AF to prevent ESRD.



Clin Res Cardiol: 02 Jul 2021; epub ahead of print
Kwon S, Lee SR, Choi EK, Jung JH, ... Oh S, Lip GYH
Clin Res Cardiol: 02 Jul 2021; epub ahead of print | PMID: 34216251
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Impact:
Abstract

Non-invasive evaluation of retinal vascular remodeling and hypertrophy in humans: intricate effect of ageing, blood pressure and glycaemia.

Gallo A, Dietenbeck T, Giron A, Paques M, Kachenoura N, Girerd X
Background
Ageing, hypertension and diabetes have an intricate effect on microvascular structure. In the retina, the respective contribution of remodeling and hypertrophy in such process is still unclear. We aimed at disentangling age, blood pressure and glycaemia effects on retinal microcirculation using the non-invasive adaptive optics ophthalmoscopy (AOO).
Methods
We included 429 subjects, distributed into 4 groups according to normal (nBP) or high blood pressure (hBP) and/or normal (nGly) or high fasting glycaemia (hGly). The nBP/nGly group was stratified in age tertiles to isolate the effect of ageing. AOO was used to measure arteriolar wall thickness (WT, µm), arteriolar (aID, µm) and venular internal diameter (vID, µm) and calculate arteriolar wall-to-lumen ratio (WLR), wall cross-sectional area (WCSA, µm2). One-way ANOVA for parametric variables and Kruskal-Wallis test for non-parametric variables were used for comparison among groups. A multivariate regression analysis including age, gender, BP, hGly and antihypertensive treatment was performed to calculate independent predictors of retinal remodeling.
Results
WT was increased with ageing (tertile1: 22.5 ± 3.2, tertile2: 24.2 ± 3.5, tertile 3: 25.2 ± 3.8, p = 0.001) and BP (hBP: 25.2 ± 4.1 vs nBP: 23.9 ± 3.7, p = 0.003). aID decreased with BP (hBP: 90.2 ± 13.4 vs nBP: 93.6 ± 11.6, p = 0.013) and increased with glycaemia (hGly: 97.7 ± 12.5 vs nGly: 93.6 ± 11.6, p = 0.002). A multivariate analysis showed independent association of hBP with WLR; hGly with WCSA; ageing with WLR and WCSA.
Conclusions
AOO non-invasively identifies retinal structural changes in human confirming that microvascular remodeling is exclusively related to hypertension, whereas vascular growth is related to ageing and hyperglycaemia.



Clin Res Cardiol: 29 Jun 2021; 110:959-970
Gallo A, Dietenbeck T, Giron A, Paques M, Kachenoura N, Girerd X
Clin Res Cardiol: 29 Jun 2021; 110:959-970 | PMID: 32494923
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Abstract

Automatic positive airway pressure for obstructive sleep apnea in heart failure with reduced ejection fraction.

Fox H, Bitter T, Sauzet O, Rudolph V, Oldenburg O
Background
Moderate-to-severe obstructive sleep apnea (OSA) is highly prevalent in heart failure patients with reduced left ventricular ejection fraction (HFrEF), and is associated with worsening cardiac function and increased mortality.
Objectives
The automatic positive airway pressure (APAP) trial tested the impact of APAP treatment on changes for the pre-specified endpoints: changes in peak oxygen uptake (peak VO2), percent-predicted peak VO2 and oxygen uptake at anaerobic threshold (VO2-AT).
Methods
This randomized, controlled pilot study included patients with chronic, stable HFrEF who had moderate-to-severe OSA. Patients were randomized 1:1 to either APAP (AutoSet™, ResMed) or nasal strips (control) for 6 months.
Results
76 patients have been randomized and 58 had complete data for final analysis. There was a statistically significant change in the APAP intervention arm for the primary endpoint percent-predicted peak VO2 in comparison to control (67 ± 17 to 73 ± 19%; p = 0.01). Additional primary endpoints peak VO2 and VO2-AT showed a trend in increase in the APAP group. Moreover, there were significant improvements within the APAP group for hypoxemia, left ventricular function and quality of life from baseline to 6 months, but not within the control group (p = 0.001 and p = 0.037, respectively).
Conclusion
APAP intervention was shown to significantly improve outcome compared to control group, represented in percent-predicted peak VO2, an established surrogate marker for cardiovascular prognosis in HFrEF. APAP has additional beneficial effects on hypoxemia, cardiac function and quality of life.



Clin Res Cardiol: 29 Jun 2021; 110:983-992
Fox H, Bitter T, Sauzet O, Rudolph V, Oldenburg O
Clin Res Cardiol: 29 Jun 2021; 110:983-992 | PMID: 32651657
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Abstract

Obstructive sleep apnoea but not central sleep apnoea is associated with left ventricular remodelling after acute myocardial infarction.

Fisser C, Götz K, Hetzenecker A, Debl K, ... Buchner S, Arzt M
Obejctive
Obstructive sleep apnoea (OSA) increases left ventricular transmural pressure more than central sleep apnoea (CSA) owing to negative intrathoracic pressure swings. We tested the hypothesis that the severity of OSA, and not CSA, is therefore associated with spheric cardiac remodelling after acute myocardial infarction.
Methods
This sub-analysis of a prospective observational study included 24 patients with acute myocardial infarction who underwent primary percutaneous coronary intervention. Spheric remodelling, calculated according to the sphericity index, was assessed by cardiac magnetic resonance imaging at baseline and 12 weeks after acute myocardial infarction. OSA and CSA [apnoea-hypopnoea index (AHI) ≥ 5/hour] were diagnosed by polysomnography.
Results
Within 12 weeks after acute myocardial infarction, patients with OSA exhibited a significant increase in systolic sphericity index compared to patients without sleep-disordered breathing (no SDB) and patients with CSA (OSA vs. CSA vs. no SDB: 0.05 ± 0.04 vs. 0.01 ± 0.04 vs. - 0.03 ± 0.03, p = 0.002). In contrast to CSA, the severity of OSA was associated with an increase in systolic sphericity index after accounting for TIMI-flow before percutaneous coronary intervention, infarct size, pain-to-balloon-time and systolic blood pressure [OSA: B (95% CI) 0.443 (0.021; 0.816), p = 0.040; CSA: 0.193 (- 0.134; 0.300), p = 0.385].
Conclusion
In contrast to CSA and no SDB, OSA is associated with spheric cardiac remodelling within the first 12 weeks after acute myocardial infarction. Data suggest that OSA-related negative intrathoracic pressure swings may contribute to this remodelling after acute myocardial infaction.



Clin Res Cardiol: 29 Jun 2021; 110:971-982
Fisser C, Götz K, Hetzenecker A, Debl K, ... Buchner S, Arzt M
Clin Res Cardiol: 29 Jun 2021; 110:971-982 | PMID: 32519084
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Impact:
Abstract

NAFLD and cardiovascular diseases: a clinical review.

Kasper P, Martin A, Lang S, Kütting F, ... Demir M, Steffen HM
Non-alcoholic fatty liver DISEASE (NAFLD) is the most common chronic liver disease in Western countries and affects approximately 25% of the adult population. Since NAFLD is frequently associated with further metabolic comorbidities such as obesity, type 2 diabetes mellitus, or dyslipidemia, it is generally considered as the hepatic manifestation of the metabolic syndrome. In addition to its potential to cause liver-related morbidity and mortality, NAFLD is also associated with subclinical and clinical cardiovascular disease (CVD). Growing evidence indicates that patients with NAFLD are at substantial risk for the development of hypertension, coronary heart disease, cardiomyopathy, and cardiac arrhythmias, which clinically result in increased cardiovascular morbidity and mortality. The natural history of NAFLD is variable and the vast majority of patients will not progress from simple steatosis to fibrosis and end stage liver disease. However, patients with progressive forms of NAFLD, including non-alcoholic steatohepatitis (NASH) and/or advanced fibrosis, as well as NAFLD patients with concomitant types 2 diabetes are at highest risk for CVD. This review describes the underlying pathophysiological mechanisms linking NAFLD and CVD, discusses the role of NAFLD as a metabolic dysfunction associated cardiovascular risk factor, and focuses on common cardiovascular manifestations in NAFLD patients.



Clin Res Cardiol: 29 Jun 2021; 110:921-937
Kasper P, Martin A, Lang S, Kütting F, ... Demir M, Steffen HM
Clin Res Cardiol: 29 Jun 2021; 110:921-937 | PMID: 32696080
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Abstract

Multi-proteomic approach to predict specific cardiovascular events in patients with diabetes and myocardial infarction: findings from the EXAMINE trial.

Ferreira JP, Sharma A, Mehta C, Bakris G, ... White WB, Zannad F
Background
Patients with diabetes who had a recent myocardial infarction (MI) are at high risk of cardiovascular events. Therefore, risk assessment is important for treatment and shared decisions. We used data from EXAMINE trial to investigate whether a multi-proteomic approach would provide specific proteomic signatures and also improve the prognostic capacity for determining the risk of cardiovascular death, MI, stroke, heart failure [HF], all-cause death, and combinations of these outcomes.
Methods
93 circulating proteins (92 from the Olink® CVDII plus troponin) were assessed in 5131 patients. Cox, competing risks, and reclassification measures were applied.
Results
The clinical model showed good discrimination and calibration for all outcomes. On top of the clinical model that included age, sex, smoking, diabetes duration, history of MI (prior to the index MI of inclusion), history of HF hospitalization, history of stroke, atrial fibrillation, hypertension, systolic blood pressure, statin therapy, estimated glomerular filtration rate, and study treatment (alogliptin or placebo), troponin and BNP added prognostic information to the composite of cardiovascular death, MI, or stroke (∆C-index + 5%) and cardiovascular death alone (∆C-index + 7%). Troponin, BNP, and TRAILR2 added prognostic information on all-cause death and the composite of cardiovascular death or HF hospitalization. HF hospitalization alone was improved by adding BNP and Gal-9. For MI, troponin, FGF23, and AMBP added prognostic value; whereas for stroke, only troponin added prognostic value (multi-proteomics improved C-index > 3% [p < 0.001] for all the studied outcomes). The addition of the final biomarker selection to the clinical model improved event reclassification (cNRI from + 23% to + 64%). Specifically, the addition of the biomarkers allowed a better classification of patients at low risk (as having \"true\" low risk) and patients and high risk (as having \"true\" high risk). These results were consistent for all the studied outcomes with even more marked differences in the fatal events.
Conclusions
The addition of multi-proteomic biomarkers to a clinical model in this population with diabetes and a recent MI allowed a better risk prediction and event reclassification, potentially helping for better risk assessment and targeted treatment decisions. T2D type 2 diabetes, MI myocardial infarction, CV cardiovascular, HFH heart failure hospitalization, Δ delta, cNRI continuous net reclassification index, BNP brain natriuretic peptide, TRAILR2 trail receptor 2 (or death receptor 5), Gal-9 galectin-9, FGF23 fibroblast growth factor 23.



Clin Res Cardiol: 29 Jun 2021; 110:1006-1019
Ferreira JP, Sharma A, Mehta C, Bakris G, ... White WB, Zannad F
Clin Res Cardiol: 29 Jun 2021; 110:1006-1019 | PMID: 32789678
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Abstract

Factors associated with in-hospital mortality and adverse outcomes during the vulnerable post-discharge phase after the first episode of acute heart failure: results of the NOVICA-2 study.

Rizzi MA, Sarasola AG, Arbé AA, Mateo SH, ... Miró Ò, ICA-SEMES Research Group
Objective
To identify patients at risk of in-hospital mortality and adverse outcomes during the vulnerable post-discharge period after the first acute heart failure episode (de novo AHF) attended at the emergency department.
Methods
This is a secondary review of de novo AHF patients included in the prospective, multicentre EAHFE (Epidemiology of Acute Heart Failure in Emergency Department) Registry. We included consecutive patients with de novo AHF, for whom 29 independent variables were recorded. The outcomes were in-hospital all-cause mortality and all-cause mortality and readmission due to AHF within 90 days post-discharge. A follow-up check was made by reviewing the hospital medical records and/or by phone.
Results
We included 3422 patients. The mean age was 80 years, 52.1% were women. The in-hospital mortality was 6.9% and was independently associated with dementia (OR = 2.25, 95% CI = 1.62-3.14), active neoplasia (1.97, 1.41-2.76), functional dependence (1.58, 1.02-2.43), chronic treatment with beta-blockers (0.62, 0.44-0.86) and severity of decompensation (6.38, 2.86-14.26 for high-/very high-risk patients). The 90-day post-discharge combined endpoint was observed in 19.3% of patients and was independently associated with hypertension (HR = 1.40, 1.11-1.76), chronic renal insufficiency (1.23, 1.01-1.49), heart valve disease (1.24, 1.01-1.51), chronic obstructive pulmonary disease (1.22, 1.01-1.48), NYHA 3-4 at baseline (1.40, 1.12-1.74) and severity of decompensation (1.23, 1.01-1.50; and 1.64, 1.20-2.25; for intermediate and high-/very high-risk patients, respectively), with different risk factors for 90-day post-discharge mortality or rehospitalisation.
Conclusions
The severity of decompensation and some baseline characteristics identified de novo AHF patients at increased risk of developing adverse outcomes during hospitalisation and the vulnerable post-discharge phase, without significant differences in these risk factors according to patient age at de novo AHF presentation.



Clin Res Cardiol: 29 Jun 2021; 110:993-1005
Rizzi MA, Sarasola AG, Arbé AA, Mateo SH, ... Miró Ò, ICA-SEMES Research Group
Clin Res Cardiol: 29 Jun 2021; 110:993-1005 | PMID: 32959081
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Abstract

Pulmonary embolism in patients with COVID-19: characteristics and outcomes in the Cardio-COVID Italy multicenter study.

Ameri P, Inciardi RM, Di Pasquale M, Agostoni P, ... Senni M, Metra M
Background
Pulmonary embolism (PE) has been described in coronavirus disease 2019 (COVID-19) critically ill patients, but the evidence from more heterogeneous cohorts is limited.
Methods
Data were retrospectively obtained from consecutive COVID-19 patients admitted to 13 Cardiology Units in Italy, from March 1st to April 9th, 2020, and followed until in-hospital death, discharge, or April 23rd, 2020. The association of baseline variables with computed tomography-confirmed PE was investigated by Cox hazards regression analysis. The relationship between D-dimer levels and PE incidence was evaluated using restricted cubic splines models.
Results
The study included 689 patients (67.3 ± 13.2 year-old, 69.4% males), of whom 43.6% were non-invasively ventilated and 15.8% invasively. 52 (7.5%) had PE over 15 (9-24) days of follow-up. Compared with those without PE, these subjects had younger age, higher BMI, less often heart failure and chronic kidney disease, more severe cardio-pulmonary involvement, and higher admission D-dimer [4344 (1099-15,118) vs. 818.5 (417-1460) ng/mL, p < 0.001]. They also received more frequently darunavir/ritonavir, tocilizumab and ventilation support. Furthermore, they faced more bleeding episodes requiring transfusion (15.6% vs. 5.1%, p < 0.001) and non-significantly higher in-hospital mortality (34.6% vs. 22.9%, p = 0.06). In multivariate regression, only D-dimer was associated with PE (HR 1.72, 95% CI 1.13-2.62; p = 0.01). The relation between D-dimer concentrations and PE incidence was linear, without inflection point. Only two subjects had a baseline D-dimer < 500 ng/mL.
Conclusions
PE occurs in a sizable proportion of hospitalized COVID-19 patients. The implications of bleeding events and the role of D-dimer in this population need to be clarified.



Clin Res Cardiol: 29 Jun 2021; 110:1020-1028
Ameri P, Inciardi RM, Di Pasquale M, Agostoni P, ... Senni M, Metra M
Clin Res Cardiol: 29 Jun 2021; 110:1020-1028 | PMID: 33141251
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Abstract

Elevated markers of thrombo-inflammatory activation predict outcome in patients with cardiovascular comorbidities and COVID-19 disease: insights from the LEOSS registry.

Cremer S, Jakob C, Berkowitsch A, Borgmann S, ... Zeiher AM, LEOSS study group
Aims
SARS-CoV-2 infection is associated with adverse outcomes in patients with cardiovascular disease. Here, we analyzed whether specific biomarkers predict the clinical course of COVID-19 in patients with cardiovascular comorbidities.
Methods and results
We enrolled 2147 patients with SARS-CoV-2 infection which were included in the Lean European Open Survey on SARS-CoV‑2 (LEOSS)-registry from March to June 2020. Clinical data and laboratory values were collected and compared between patients with and without cardiovascular comorbidities in different clinical stages of the disease. Predictors for mortality were calculated using multivariate regression analysis. We show that patients with cardiovascular comorbidities display significantly higher markers of myocardial injury and thrombo-inflammatory activation already in the uncomplicated phase of COVID-19. In multivariate analysis, elevated levels of troponin [OR 1.54; (95% CI 1.22-1.96), p < 0.001)], IL-6 [OR 1.69 (95% CI 1.26-2.27), p < 0.013)], and CRP [OR 1.32; (95% CI 1.1-1.58), p < 0.003)] were predictors of mortality in patients with COVID-19.
Conclusion
Patients with cardiovascular comorbidities show elevated markers of thrombo-inflammatory activation and myocardial injury, which predict mortality, already in the uncomplicated phase of COVID-19. Starting targeted anti-inflammatory therapy and aggressive anticoagulation already in the uncomplicated phase of the disease might improve outcomes after SARS-CoV-2 infection in patients with cardiovascular comorbidities. Elevated markers of thrombo-inflammatory activation predict outcome in patients with cardiovascular comorbidities and COVID-19 disease: insights from the LEOSS registry.



Clin Res Cardiol: 29 Jun 2021; 110:1029-1040
Cremer S, Jakob C, Berkowitsch A, Borgmann S, ... Zeiher AM, LEOSS study group
Clin Res Cardiol: 29 Jun 2021; 110:1029-1040 | PMID: 33211155
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Abstract

Guideline-directed medical therapy in real-world heart failure patients with low blood pressure and renal dysfunction.

Chen X, Cui X, Thunström E, Pivodic A, Dahlström U, Fu M
Background
Among patients with heart failure and reduced ejection fraction (HFrEF), angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEI/ARB), β-blockers (BB) and mineralocorticoid receptor antagonist (MRA) are known as guideline-directed medical therapy to improve prognosis. However, low blood pressure (BP) and renal dysfunction are often challenges prevent clinical implementation, so we investigated the association of different combinations of GDMT treatments with all-cause mortality in HFrEF population with low BP and renal dysfunction.
Methods
This study initially included 51, 060 HF patients from the Swedish Heart Failure Registry, and finally 1464 HFrEF patients with low BP (systolic BP ≦ 100 mmHg) and renal dysfunction (estimated glomerular filtration rate (eGFR) ≦ 60 ml/min/1.73m2) were ultimately enrolled. Patients were receiving oral medication for HF at study enrollment, and divided into four groups (group 1-4: ACEI/ARB + BB + MRA, ACEI/ARB + BB, ACEI/ARB + MRA or ACEI/ARB only, and other). The outcome is time to all-cause mortality.
Results
Among the study patients, 485 (33.1%), 672 (45.9%), 109 (7.4%) and 198 (13.5%) patients were in group 1-4. Patients in group 1 were younger, had highest hemoglobin, and most with EF < 30%. During a median of 1.33 years follow-up, 937 (64%) patients died. After adjustment for age, gender, LVEF, eGFR, hemoglobin when compared with the group 1, the hazard ratio for all-cause mortality in group 2 was 1.04 (0.89-1.21) (p = 0.62), group 3 1.40 (1.09-1.79) (p = 0.009), and group 4 1.71 (1.39-2.09) (p < 0.001).
Conclusions
In real-world HFrEF patients with low BP and renal dysfunction, full medication of guideline-directed medical therapy is associated with improved survival. The benefit was larger close to the index date and decreased with follow-up time.



Clin Res Cardiol: 29 Jun 2021; 110:1051-1062
Chen X, Cui X, Thunström E, Pivodic A, Dahlström U, Fu M
Clin Res Cardiol: 29 Jun 2021; 110:1051-1062 | PMID: 33394127
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Abstract

Impact of oral anticoagulation on clinical outcomes of COVID-19: a nationwide cohort study of hospitalized patients in Germany.

Fröhlich GM, Jeschke E, Eichler U, Thiele H, ... Landmesser U, Günster C
Objectives
The aim of this study was to investigate the impact of concomitant long-term medication-with a focus on ACE inhibitors and oral anticoagulation-on clinical outcomes in patients hospitalized with coronavirus disease 2019.
Methods
This is a retrospective cohort study using claims data of the biggest German health insurance company AOK, covering 26.9 million people all over Germany. In particular, patient-related characteristics and co-medication were evaluated. A multivariable logistic regression model was adopted to identify independent predictors for the primary outcome measure of all-cause mortality or need for invasive or non-invasive ventilation or extracorporeal membrane oxygenation.
Results
6637 patients in 853 German hospitals were included. The primary outcome occurred in 1826 patients (27.5%). 1372 patients (20.7%) died, 886 patients (13.3%) needed respiratory support, and 53 patients (0.8%) received extracorporeal membrane oxygenation. 34 of these patients survived (64.2%). The multivariable model demonstrated that pre-existing oral anticoagulation therapy with either vitamin-K antagonists OR 0.57 (95% CI 0.40-0.83, p = 0.003) or direct oral anticoagulants OR 0.71 (95% CI 0.56-0.91, p = 0.007)-but not with antiplatelet therapy alone OR 1.10 (95% CI 0.88-1.23, p = 0.66)-was associated with a lower event rate. This finding was confirmed in a propensity match analysis.
Conclusions
In a multivariable analysis, a therapy with both direct oral anticoagulants or vitamin-K antagonists-but not with antiplatelet therapy-was associated with improved clinical outcomes. ACE inhibitors did not impact outcomes. Prospective randomized trials are needed to verify this hypothesis.



Clin Res Cardiol: 29 Jun 2021; 110:1041-1050
Fröhlich GM, Jeschke E, Eichler U, Thiele H, ... Landmesser U, Günster C
Clin Res Cardiol: 29 Jun 2021; 110:1041-1050 | PMID: 33416918
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Abstract

Short-term cardiac outcome in survivors of COVID-19: a systematic study after hospital discharge.

Sechi LA, Colussi G, Bulfone L, Brosolo G, ... Tascini C, Catena C
Background
COVID-19 has caused considerable morbidity and mortality worldwide and cardiac involvement has been reported during infection. The short-term cardiac outcome in survivors of COVID-19 is not known.
Objective
To examine the heart of patients who survived COVID-19 and to compare the cardiac outcome between patients who recovered from mild-to-moderate or severe illness.
Methods
With use of ECG and echocardiography, we examined the heart of 105 patients who had been hospitalized with COVID-19 and were consecutively recruited after hospital discharge while attending follow-up visits. Survivors of COVID-19 were compared with 105 matched controls. We also compared the cardiac outcome and lung ultrasound scan between COVID-19 patients who had mild-to-moderate or severe illness.
Results
Cardiac data were collected a median of 41 days from the first detection of COVID-19. Symptoms were present in a low percentage of patients. In comparison with matched controls, no considerable structural or functional differences were observed in the heart of survivors of COVID-19. Lung ultrasound scan detected significantly greater residual pulmonary involvement in COVID-19 patients who had recovered from severe than mild-to-moderate illness. No significant differences were detected in ECG tracings nor were found in the left and right ventricular function of patients who had recovered from mild-to-moderate or severe illness.
Conclusions
In a short-term follow-up, no abnormalities were identified in the heart of survivors of COVID-19, nor cardiac differences were detected between patients who had different severity of illness. With the limitations of a cross-sectional study, these findings suggest that patients who recover from COVID-19 do not have considerable cardiac sequelae.



Clin Res Cardiol: 29 Jun 2021; 110:1063-1072
Sechi LA, Colussi G, Bulfone L, Brosolo G, ... Tascini C, Catena C
Clin Res Cardiol: 29 Jun 2021; 110:1063-1072 | PMID: 33481096
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Abstract

The importance of including uric acid in the definition of metabolic syndrome when assessing the mortality risk.

Pugliese NR, Mengozzi A, Virdis A, Casiglia E, ... Borghi C, Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension
Introduction
Serum uric acid (SUA) has been depicted as a contributory causal factor in metabolic syndrome (MS), which in turn, portends unfavourable prognosis.
Aim
We assessed the prognostic role of SUA in patients with and without MS.
Methods
We used data from the multicentre Uric Acid Right for Heart Health study and considered cardiovascular mortality (CVM) as death due to fatal myocardial infarction, stroke, sudden cardiac death, or heart failure.
Results
A total of 9589 subjects (median age 58.5 years, 45% males) were included in the analysis, and 5100 (53%) patients had a final diagnosis of MS. After a median follow-up of 142 months, we observed 558 events. Using a previously validated cardiovascular SUA cut-off to predict CVM (> 5.1 mg/dL in women and 5.6 mg/dL in men), elevated SUA levels were significantly associated to a worse outcome in patients with and without MS (all p < 0.0001) and provided a significant net reclassification improvement of 7.1% over the diagnosis of MS for CVM (p = 0.004). Cox regression analyses identified an independent association between SUA and CVM (Hazard Ratio: 1.79 [95% CI, 1.15-2.79]; p < 0.0001) after the adjustment for MS, its single components and renal function. Three specific combinations of the MS components were associated with higher CVM when increasing SUA levels were reported, and systemic hypertension was the only individual component ever-present (all p < 0.0001).
Conclusion
Increasing SUA levels are associated with a higher CVM risk irrespective of the presence of MS: a cardiovascular SUA threshold may improve risk stratification.



Clin Res Cardiol: 29 Jun 2021; 110:1073-1082
Pugliese NR, Mengozzi A, Virdis A, Casiglia E, ... Borghi C, Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension
Clin Res Cardiol: 29 Jun 2021; 110:1073-1082 | PMID: 33604722
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Abstract

Impact of chronic obstructive pulmonary disease on 10-year mortality after percutaneous coronary intervention and bypass surgery for complex coronary artery disease: insights from the SYNTAX Extended Survival study.

Wang R, Tomaniak M, Takahashi K, Gao C, ... Onuma Y, Serruys PW
Aims
To evaluate the impact of chronic obstructive pulmonary disease (COPD) on 10-year all-cause death and the treatment effect of CABG versus PCI on 10-year all-cause death in patients with three-vessel disease (3VD) and/or left main coronary artery disease (LMCAD) and COPD.
Methods
Patients were stratified according to COPD status and compared with regard to clinical outcomes. Ten-year all-cause death was examined according to the presence of COPD and the revascularization strategy.
Results
COPD status was available for all randomized 1800 patients, of whom, 154 had COPD (8.6%) at the time of randomization. Regardless of the revascularization strategy, patients with COPD had a higher risk of 10-year all-cause death, compared with those without COPD (43.1% vs. 24.9%; hazard ratio [HR]: 2.03; 95% confidence interval [CI]: 1.56-2.64; p < 0.001). Among patients with COPD, CABG appeared to have a slightly lower risk of 10-year all-cause death compared with PCI (42.3% vs. 43.9%; HR: 0.96; 95% CI: 0.59-1.56, p = 0.858), whereas among those without COPD, CABG had a significantly lower risk of 10-year all-cause death (22.7% vs. 27.1%; HR: 0.81; 95% CI: 0.67-0.99, p = 0.041). There was no significant differential treatment effect of CABG versus PCI on 10-year all-cause death between patients with and without COPD (p interaction = 0.544).
Conclusions
COPD was associated with a higher risk of 10-year all-cause death after revascularization for complex coronary artery disease. The presence of COPD did not significantly modify the beneficial effect of CABG versus PCI on 10-year all-cause death.
Trial registration
SYNTAX: ClinicalTrials.gov reference: NCT00114972. SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050.



Clin Res Cardiol: 29 Jun 2021; 110:1083-1095
Wang R, Tomaniak M, Takahashi K, Gao C, ... Onuma Y, Serruys PW
Clin Res Cardiol: 29 Jun 2021; 110:1083-1095 | PMID: 33710385
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Abstract

Early onset of hyperuricemia is associated with increased cardiovascular disease and mortality risk.

Li L, Zhao M, Wang C, Zhang S, ... Wu S, Xue H
Background
Hyperuricemia is associated with cardiovascular mortality, but the association of the age at hyperuricemia onset with cardiovascular disease (CVD) and mortality is still unclear.
Objective
The purpose of this study was to examine the associations of hyperuricemia onset age with CVD and all-cause mortality.
Methods
A total of 82,219 participants free of hyperuricemia and CVD from 2006 to 2015 in the Kailuan study were included. The analysis cohort comprised 18,311 new-onset hyperuricemia patients and controls matched for age and sex from the general population. Adjusted associations were estimated using Cox models for CVD and all-cause mortality across a range of ages.
Results
There were 1,021 incident cases of CVD (including 215 myocardial infarctions, 814 strokes) and 1459 deaths during an average of 5.2 years of follow-up. Patients with hyperuricemia onset at an age < 45 years had the highest hazard ratios (HRs) (1.78 (1.14-2.78) for CVD and 1.64 (1.04-2.61) for all-cause mortality relative to controls). The HRs of CVD and all-cause mortality were 1.32 (1.05-1.65) and 1.40 (1.08-1.81) for the 45-54 years age group, 1.23 (0.97-1.56) and 1.37 (1.11 to 1.72) for the 55-64 years age group, and 1.10 (0.88-1.39) and 0.88 (0.76-1.01) for the ≥ 65 years age group, respectively.
Conclusions
The age at hyperuricemia onset was identified as an important predictor of CVD and all-cause mortality risk, and the prediction was more powerful in those with a younger age of hyperuricemia onset. Early onset of hyperuricemia is associated with increased cardiovascular disease and mortality risk.



Clin Res Cardiol: 29 Jun 2021; 110:1096-1105
Li L, Zhao M, Wang C, Zhang S, ... Wu S, Xue H
Clin Res Cardiol: 29 Jun 2021; 110:1096-1105 | PMID: 33846840
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Abstract

Non-aortic cardiovascular disease in Marfan syndrome: a nationwide epidemiological study.

Andersen NH, Groth KA, Berglund A, Hove H, Gravholt CH, Stochholm K
Objectives
Studies indicate that other cardiovascular problems than aortic disease are a burden for patients with Marfan syndrome (MFS). The aim of the study was to assess the extent of this issue.
Methods
A registry-based population study of patients with a Ghent II verified MFS diagnosis. Each patient was matched with up to 100 controls on age and sex. From the Danish healthcare system, we identified 407 MFS patients (from 1977 to 2014) and their cardiovascular events and compared them with those in 40,700 controls. Total follow-up time was 16,439 person years.
Results
Mitral valve disease was significantly more common in MFS [HR: 58.9 (CI 38.1-91.1)] and happened earlier and more often in women than men with MFS [age at first registration: 22 vs. 38 years, HR: 2.1 (CI 1.0-4.4)]. Heart failure/cardiomyopathy was also more common in MFS [HR: 8.7 (CI 5.7-13.4)] and men were more affected than women, and at younger age [39 vs. 64 years, HR: 0.18 (CI 0.06-0.55)]. In all cases, atrioventricular block [HR: 4.9 (1.5-15.6)] was related to heart surgery. Supraventricular [HR: 9.7 (CI 7.5-12.7)] and ventricular tachycardia [HR: 7.7 (CI 4.2-14.3)] also occurred more often than in the control group. The risk of sudden cardiac death was increased [HR: 8.3 (CI 3.8-18.0)] but the etiology was unclear due to lack of autopsies.
Conclusion
Non-aortic cardiovascular disease in patients with MFS is exceptionally prevalent and the range of diseases varies between women and men. Physicians caring for MFS patients must be aware of this large spectrum of cardiovascular diseases.



Clin Res Cardiol: 29 Jun 2021; 110:1106-1115
Andersen NH, Groth KA, Berglund A, Hove H, Gravholt CH, Stochholm K
Clin Res Cardiol: 29 Jun 2021; 110:1106-1115 | PMID: 33885997
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Abstract

Sex disparities and adverse cardiovascular and kidney outcomes in patients with chronic kidney disease: results from the KNOW-CKD.

Jung CY, Heo GY, Park JT, Joo YS, ... Ahn C, Han SH
Aims
Longitudinal studies of the association between sex and adverse clinical outcomes in patients with chronic kidney disease (CKD) are scarce. We assessed whether major outcomes may differ by sex among CKD patients.
Methods
We analyzed a total of 1780 participants with non-dialysis CKD G1-5 from the KoreaN cohort study for Outcome in patients with Chronic Kidney Disease (KNOW-CKD). The primary outcome was a composite of non-fatal cardiovascular events or all-cause mortality. Secondary outcomes included fatal and non-fatal cardiovascular events, all-cause mortality, and a composite kidney outcome of ≥ 50% decline in estimated glomerular filtration rate from baseline or the onset of end-stage kidney disease.
Results
There were 1088 (61%) men and 692 (39%) women in the study cohort. The proportion of smokers was significantly higher in men (24% vs. 3%). During 8430 person-years of follow-up, 201 primary outcome events occurred: 144 (13%) in men and 57 (8%) in women, with corresponding incidence rates of 2.9 and 1.7 per 100 person-years, respectively. In multivariable Cox models, men were associated with a 1.58-fold (95% CI 1.06-2.35) higher risk of composite outcome. Propensity score matching analysis revealed similar findings (HR 1.81; 95% CI 1.14-2.91). Risk of all-cause mortality was significantly higher in men of the matched cohort. However, there was no difference in the risk of CKD progression. In the subgroup with coronary artery calcium (CAC) measurements, men had a higher likelihood of CAC progression.
Conclusions
In Korean CKD patients, men were more likely to experience adverse cardiovascular events and death than women.



Clin Res Cardiol: 29 Jun 2021; 110:1116-1127
Jung CY, Heo GY, Park JT, Joo YS, ... Ahn C, Han SH
Clin Res Cardiol: 29 Jun 2021; 110:1116-1127 | PMID: 34003323
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Abstract

Expert opinion paper on cardiac imaging after ischemic stroke.

Schnabel RB, Camen S, Knebel F, Hagendorff A, ... Wachter R, Haeusler KG
This expert opinion paper on cardiac imaging after acute ischemic stroke or transient ischemic attack (TIA) includes a statement of the \"Heart and Brain\" consortium of the German Cardiac Society and the German Stroke Society. The Stroke Unit-Commission of the German Stroke Society and the German Atrial Fibrillation NETwork (AFNET) endorsed this paper. Cardiac imaging is a key component of etiological work-up after stroke. Enhanced echocardiographic tools, constantly improving cardiac computer tomography (CT) as well as cardiac magnetic resonance imaging (MRI) offer comprehensive non- or less-invasive cardiac evaluation at the expense of increased costs and/or radiation exposure. Certain imaging findings usually lead to a change in medical secondary stroke prevention or may influence medical treatment. However, there is no proof from a randomized controlled trial (RCT) that the choice of the imaging method influences the prognosis of stroke patients. Summarizing present knowledge, the German Heart and Brain consortium proposes an interdisciplinary, staged standard diagnostic scheme for the detection of risk factors of cardio-embolic stroke. This expert opinion paper aims to give practical advice to physicians who are involved in stroke care. In line with the nature of an expert opinion paper, labeling of classes of recommendations is not provided, since many statements are based on expert opinion, reported case series, and clinical experience.



Clin Res Cardiol: 29 Jun 2021; 110:938-958
Schnabel RB, Camen S, Knebel F, Hagendorff A, ... Wachter R, Haeusler KG
Clin Res Cardiol: 29 Jun 2021; 110:938-958 | PMID: 34143285
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Abstract

Serum markers of fibrosis, cardiovascular and all-cause mortality in hemodialysis patients: the AURORA trial.

Salib M, Girerd S, Girerd N, März W, ... Rossignol P, Zannad F
Background
Biomarkers of fibrosis are associated with outcome in several cardiovascular diseases. However, their relevance to chronic kidney disease and dialysis is uncertain, as it remains unclear how the kidneys and the dialysis procedure itself affect their elimination and degradation. We aimed to investigate the relationship of the blood levels of two markers associated with fibrosis: procollagen type I C-terminal pro-peptide (PICP) and galectin-3 (Gal-3) with mortality in dialysis patients.
Methods
Procollagen type I C-terminal pro-peptide and galectin-3 were measured at baseline in 2773 patients enrolled in the AURORA trial, investigating the effect of rosuvastatin on cardiovascular outcomes, in patients on hemodialysis, and their interaction with CV death or all-cause mortality using survival models. The added prognostic value of these biomarkers was assessed by the net reclassification improvement (NRI).
Results
The median follow-up period was 3.8 years. Blood concentrations of PICP and Gal-3 were significantly associated with CV death [adjusted HR per 1 SD = 1.11 (1.02-1.20) and SD = 1.20 (1.10-1.31), respectively] and all-cause mortality (all adjusted p < 0.001). PICP and Gal-3 had a synergistic effect with regard to CV death and all-cause mortality (interaction p = 0.04 and 0.01, respectively). Adding PICP, Gal-3 and their interaction on top of clinical and biological covariates, resulted in significantly improved prognostic accuracy NRI = 0.080 (0.019-0.143) for CV death.
Conclusion
In dialysis patients, concomitant increase in PICP and Gal-3 concentrations are associated with higher rates of CV death. These results suggest that concomitantly raised PICP and Gal-3 may reflect an activated fibrogenesis relevant to risk stratification in dialysis, raising the hypothesis that anti-fibrotic therapy may be beneficial for cardiovascular protection in such patients.



Clin Res Cardiol: 24 Jun 2021; epub ahead of print
Salib M, Girerd S, Girerd N, März W, ... Rossignol P, Zannad F
Clin Res Cardiol: 24 Jun 2021; epub ahead of print | PMID: 34170371
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Impact:
Abstract

Factors associated with a high or low implantation of self-expanding devices in TAVR.

Veulemans V, Maier O, Piayda K, Berning KL, ... Kelm M, Zeus T
Objectives
Optimizing valve implantation depth (ID) plays a crucial role in minimizing conduction disturbances and achieving optimal functional integrity. Until now, the impact of intraprocedural fast (FP) or rapid ventricular pacing (RP) on the implantation depth has not been investigated. Therefore, we aimed to (1) evaluate the impact of different pacing maneuvers on ID, and (2) identify the independent predictors of deep ID.
Methods
473 TAVR patients with newer-generation self-expanding devices were retrospectively enrolled and one-to-one propensity-score-matching was performed, resulting in a matching of 189 FP and RP patients in each cohort. The final ID was analyzed, and the underlying functional, anatomical, and procedural conditions were evaluated by univariate and multivariate analysis.
Results
The highest ID was reached under RP in severe aortic valve calcification and valve size 26 mm. Multivariate analysis identified left ventricular outflow (LVOT) calcification [OR 0.50 (0.31-0.81) p = 0.005*], a \"flare\" aortic root [OR 0.42 (0.25-0.71), p = 0.001*], and RP (OR 0.49 [0.30-0.79], p = 0.004*) as independent highly preventable predictors of a deep ID. In a model of protective factors, ID was significantly reduced with the number of protective criteria (0-2 criteria: - 5.7 mm ± 2.6 vs. 3-4 criteria - 4.3 mm ± 2.0; p < 0.0001*).
Conclusion
Data from this retrospective analysis indicate that RP is an independent predictor to reach a higher implantation depth using self-expanding devices. Randomized studies should prove for validation compared to fast and non-pacing maneuvers during valve delivery and their impact on implantation depth.
Trail registration
Clinical Trial registration: NCT01805739.
Study design
Evaluation of the impact of different pacing maneuvers (fast ventricular pacing-FP vs. rapid ventricular pacing-RP) on implantation depth (ID). After one-to-one-propensity-score-matching, independent protective and risk factors for a very deep ID beneath 6 mm toward the LVOT (< - 6 mm) were identified. Stent frame pictures as a courtesy by Medtronic®. AVC aortic valve calcification.



Clin Res Cardiol: 23 Jun 2021; epub ahead of print
Veulemans V, Maier O, Piayda K, Berning KL, ... Kelm M, Zeus T
Clin Res Cardiol: 23 Jun 2021; epub ahead of print | PMID: 34165599
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Impact:
Abstract

Cardiovascular profiling in the diabetic continuum: results from the population-based Gutenberg Health Study.

Schmitt VH, Leuschner A, Jünger C, Pinto A, ... Wild PS, Münzel T
Aims
To assess the prevalence of type 2 diabetes mellitus (T2DM) and prediabetes in the general population and to investigate the associated cardiovascular burden and clinical outcome.
Methods and results
The study sample comprised 15,010 individuals aged 35-74 years of the population-based Gutenberg Health Study. Subjects were classified into euglycaemia, prediabetes and T2DM according to clinical and metabolic (HbA1c) information. The prevalence of prediabetes was 9.5% (n = 1415) and of T2DM 8.9% (n = 1316). Prediabetes and T2DM showed a significantly increased prevalence ratio (PR) for age, obesity, active smoking, dyslipidemia, and arterial hypertension compared to euglycaemia (for all, P < 0.0001). In a robust Poisson regression analysis, prediabetes was established as an independent predictor of clinically-prevalent cardiovascular disease (PRprediabetes 1.20, 95% CI 1.07-1.35, P = 0.002) and represented as a risk factor for asymptomatic cardiovascular organ damage independent of traditional risk factors (PR 1.04, 95% CI 1.01-1.08, P = 0.025). Prediabetes was associated with a 1.5-fold increased 10-year risk for cardiovascular disease compared to euglycaemia. In Cox regression analysis, prediabetes (HR 2.10, 95% CI 1.76-2.51, P < 0.0001) and T2DM (HR 4.28, 95% CI 3.73-4.92, P < 0.0001) indicated for an increased risk of death. After adjustment for age, sex and traditional cardiovascular risk factors, only T2DM (HR 1.89, 95% CI 1.63-2.20, P < 0.0001) remained independently associated with increased all-cause mortality.
Conclusion
Besides T2DM, also prediabetes inherits a significant cardiovascular burden, which translates into poor clinical outcome and indicates the need for new concepts regarding the prevention of cardiometabolic disorders.



Clin Res Cardiol: 23 Jun 2021; epub ahead of print
Schmitt VH, Leuschner A, Jünger C, Pinto A, ... Wild PS, Münzel T
Clin Res Cardiol: 23 Jun 2021; epub ahead of print | PMID: 34169342
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Impact:
Abstract

Cardiac autonomic function and cognitive performance in patients with atrial fibrillation.

Hämmerle P, Aeschbacher S, Springer A, Eken C, ... Kühne M, Zuern CS
Background
Atrial fibrillation (AF) is associated with loss of cognition and dementia. Cardiac autonomic dysfunction has been linked to cognitive decline. We aimed to investigate if reduced cardiac autonomic function (CAF) is associated with cognitive impairment in AF patients.
Methods
Patients with paroxysmal, persistent and permanent AF were enrolled from a multicenter cohort study if they had AF (\"AF group\") or sinus rhythm (\"SR group\") on a baseline 5 min ECG recording. Parameters quantifying CAF (heart rate variability triangular index (HRVI), mean heart rate (MHR), RMSSD, SDNN, total power and power in the VLF, LF, HF ranges) were calculated. We used the Montreal Cognitive Assessment (MoCA) to assess global cognitive function.
Results
1685 AF patients with a mean age of 73 ± 8 years, 29% females, were included. MoCA score was 24.5 ± 3.2 in the AF group (N = 710 patients) and 25.4 ± 3.2 in the SR group (N = 975 patients). After adjusting for multiple confounders, lower HRVI was associated with lower MoCA scores, both in the SR group [β = 0.049; 95% confidence interval (CI) 0.016-0.081; p = 0.003] and in the AF group (β = 0.068; 95% CI 0.020-0.116; p = 0.006). In the AF group, higher MHR was associated with a poorer performance in the MoCA (β =  - 0.008; 95% CI - 0.014 to - 0.002; p = 0.014). We found no convincing evidence of association for other CAF parameters with cognition.
Conclusion
Our data suggest that impaired CAF is associated with worse cognitive performance in patients with AF. Among standard HRV parameters, HRVI might be the most promising ECG index.
Trial registration
ClinicalTrials.gov Identifier: NCT02105844.



Clin Res Cardiol: 21 Jun 2021; epub ahead of print
Hämmerle P, Aeschbacher S, Springer A, Eken C, ... Kühne M, Zuern CS
Clin Res Cardiol: 21 Jun 2021; epub ahead of print | PMID: 34156525
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Impact:
Abstract

Prevention of coronary obstruction in patients at risk undergoing transcatheter aortic valve implantation: the Hamburg BASILICA experience.

Westermann D, Ludwig S, Kalbacher D, Spink C, ... Conradi L, Schirmer J
Objectives
This study aimed to assess the clinical outcome of the bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary obstruction (BASILICA) technique in a single-center patient cohort considered at high or prohibitive risk of transcatheter aortic valve implantation (TAVI)-induced coronary obstruction.
Methods
Between October 2019 and January 2021, a total of 15 consecutive patients (age 81.0 [78.1, 84.4] years; 53.3% female; EuroSCORE II 10.6 [6.3, 14.8] %) underwent BASILICA procedure prior to TAVI at our institution. Indications for TAVI were degeneration of stented (n = 12, 80.0%) or stentless (n = 1, 6.7%) bioprosthetic aortic valves, or calcific stenosis of native aortic valves (n = 2, 13.3%), respectively. Individual risk of TAVI-induced coronary obstruction was assessed by pre-procedural computed tomography analysis. Procedural and 30-day outcomes were documented in accordance with Valve Academic Research Consortium (VARC)-2 criteria.
Results
BASILICA was attempted for single left coronary cusp in 12 patients (80.0%), for single right coronary cusp in 2 patients (13.3%), and for both cusps in 1 patient (6.7%), respectively. The procedure was feasible in 13 patients (86.7%) resulting in effective prevention of coronary obstruction, whilst TAVI was performed without prior successful bioprosthetic leaflet laceration in two patients (13.3%). In one of these patients (6.7%), additional chimney stenting immediately after TAVI was performed. No all-cause deaths or strokes were documented after 30 days.
Conclusion
The BASILICA technique appears to be a feasible, safe and effective concept to avoid iatrogenic coronary artery obstruction during TAVI in both native and bioprosthetic valves of patients at high or prohibitive risk. ClinicalTrials.gov Identifier: NCT04227002 (Hamburg AoRtic Valve cOhoRt).

© 2021. The Author(s).

Clin Res Cardiol: 21 Jun 2021; epub ahead of print
Westermann D, Ludwig S, Kalbacher D, Spink C, ... Conradi L, Schirmer J
Clin Res Cardiol: 21 Jun 2021; epub ahead of print | PMID: 34156524
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Impact:
Abstract

Remote proctoring for high-risk coronary interventions with mechanical circulatory support during COVID-19 pandemic and beyond.

Woitek FJ, Haussig S, Mierke J, Linke A, Mangner N
Remote proctoring by advanced digital technologies may help to overcome pandemic, geographic, and resource-related constraints for mentoring and educating interventional cardiology skills. We present a case series of patients undergoing high-risk percutaneous coronary intervention (HR-PCI) with mechanical circulatory support (MCS) guided by remote proctoring to gain insights into a streaming technology platform with regard to video/audio quality, visibility of all structural and imaging details, and delay in transmission. According to our experience, remote proctoring appears to be a reliable, quick, and resource-conserving way to disseminate, educate and improve MCS-supported HR-PCI with implications far beyond the COVID-19 pandemic.



Clin Res Cardiol: 21 Jun 2021; epub ahead of print
Woitek FJ, Haussig S, Mierke J, Linke A, Mangner N
Clin Res Cardiol: 21 Jun 2021; epub ahead of print | PMID: 34156523
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Impact:
Abstract

Ten-year clinical outcomes of polymer-free versus durable polymer new-generation drug-eluting stent in patients with coronary artery disease with and without diabetes mellitus : Results of the Intracoronary Stenting and Angiographic Results: Test Efficacy of Sirolimus- and Probucol- and Zotarolimus-Eluting Stents (ISAR-TEST 5) trial.

Koch T, Lenz T, Joner M, Xhepa E, ... Kufner S, Intracoronary Stenting and Angiographic Results: Test Efficacy of Sirolimus- and Probucol-Eluting Versus Zotarolimus- Eluting Stents (ISAR-TEST 5) Investigators
Background
Very long-term outcomes according to diabetic status of patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) with new-generation drug-eluting stents (DES) are scant. Both, the durable polymer zotarolimus-eluting stent (DP-ZES), the first DES to gain FDA-approval for specific use in patients with diabetes mellitus, and the polymer-free sirolimus- and probucol-eluting stent (PF-SES), with a unique design that enables effective drug release without the need of a polymer offer the potential to enhance clinical long-term outcomes especially in patients with diabetes mellitus.
Methods
We investigate 10-year clinical outcomes of the prespecified subgroups of patients with and without diabetes mellitus, randomly assigned to treatment with PF-SES versus DP-ZES in the ISAR-TEST 5 trial. The primary endpoint of interest was major adverse cardiac events (MACE), defined as the composite of all-cause death, any myocardial infarction or any revascularization. Further endpoints of interest were cardiac death, myocardial infarction related to the target vessel and target lesion revascularization as well as the individual components of the primary composite endpoint and the incidence of definite or probable stent thrombosis at 10 years.
Results
This analysis includes a total of 3002 patients randomly assigned to PF-SES (n = 2002) or DP-ZES (n = 1000). Prevalence of diabetes mellitus was high and comparable, 575 Patients (28.7%) in PF-SES group and 295 patients (29.5%) in DP-ZES group (P = 0.66). At 10 years 53.5% of patients with diabetes mellitus and 68.5% of patients without diabetes mellitus were alive. Regarding major adverse cardiac events, PF-SES as compared to DP-ZES showed comparable event rates in patients with diabetes mellitus (74.8% vs. 79.6%; hazard ratio 0.86; 95% CI 0.73-1.02; P = 0.08) and in patients without diabetes (PF-SES 62.5% vs. DP-ZES 62.2%; hazard ratio 0.99; 95% CI 0.88-1.11; P = 0.88).
Conclusion
At 10 years, both new-generation DES show comparable clinical outcome irrespective of diabetic status or polymer strategy. Event rates after PCI in patients with diabetes mellitus are considerable higher than in patients without diabetes mellitus and continue to accrue over time.
Trial registration
ClinicalTrials.gov, NCT00598533, Registered 10 January 2008, https://clinicaltrials.gov/ct2/show/NCT00598533?term=NCT00598533 Kaplan-Meier estimates of endpoints of interest for patients with vs. without diabetes mellitus treated with PF-SES vs. DP-ZES. Bar graphs: Kaplan-Meier estimates as percentages. PF-SES: polymer-free sirolimus-eluting stent; DP-ZES: durable polymer zotarolimus-eluting stent; DM: diabetes mellitus. Comparison of event rates of individual endpoints in patients with and without diabetes mellitus treated with PF-SES vs. DP-ZES all without statistically significant differences. Comparison of event rates of individual endpoints in overall patients with vs. without diabetes mellitus significantly different (P ≤ 0.01 for all comparisons).



Clin Res Cardiol: 21 Jun 2021; epub ahead of print
Koch T, Lenz T, Joner M, Xhepa E, ... Kufner S, Intracoronary Stenting and Angiographic Results: Test Efficacy of Sirolimus- and Probucol-Eluting Versus Zotarolimus- Eluting Stents (ISAR-TEST 5) Investigators
Clin Res Cardiol: 21 Jun 2021; epub ahead of print | PMID: 34156521
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Impact:
Abstract

Establishing a cardiac training group for patients with heart failure: the \"HIP-in-Würzburg\" study.

Güder G, Wilkesmann J, Scholz N, Leppich R, ... Breunig M, Störk S
Background
Exercise training in heart failure (HF) is recommended but not routinely offered, because of logistic and safety-related reasons. In 2020, the German Society for Prevention&Rehabilitation and the German Society for Cardiology requested establishing dedicated \"HF training groups.\" Here, we aimed to implement and evaluate the feasibility and safety of one of the first HF training groups in Germany.
Methods
Twelve patients (three women) with symptomatic HF (NYHA class II/III) and an ejection fraction ≤ 45% participated and were offered weekly, physician-supervised exercise training for 1 year. Patients received a wrist-worn pedometer (M430 Polar) and underwent the following assessments at baseline and after 4, 8 and 12 months: cardiopulmonary exercise test, 6-min walk test, echocardiography (blinded reading), and quality of life assessment (Kansas City Cardiomyopathy Questionnaire, KCCQ).
Results
All patients (median age [quartiles] 64 [49; 64] years) completed the study and participated in 76% of the offered 36 training sessions. The pedometer was worn ≥ 1000 min per day over 86% of the time. No cardiovascular events occurred during training. Across 12 months, NT-proBNP dropped from 986 pg/ml [455; 1937] to 483 pg/ml [247; 2322], and LVEF increased from 36% [29;41] to 41% [32;46]%, (p for trend = 0.01). We observed no changes in exercise capacity except for a subtle increase in peak VO2% predicted, from 66.5 [49; 77] to 67 [52; 78]; p for trend = 0.03. The physical function and social limitation domains of the KCCQ improved from 60 [54; 82] to 71 [58; 95, and from 63 [39; 83] to 78 [64; 92]; p for trend = 0.04 and = 0.01, respectively. Positive trends were further seen for the clinical and overall summary scores.
Conclusion
This pilot study showed that the implementation of a supervised HF-exercise program is feasible, safe, and has the potential to improve both quality of life and surrogate markers of HF severity. This first exercise experiment should facilitate the design of risk-adopted training programs for patients with HF.



Clin Res Cardiol: 21 Jun 2021; epub ahead of print
Güder G, Wilkesmann J, Scholz N, Leppich R, ... Breunig M, Störk S
Clin Res Cardiol: 21 Jun 2021; epub ahead of print | PMID: 34159415
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Impact:
Abstract

The ACURATE neo2 valve system for transcatheter aortic valve implantation: 30-day and 1-year outcomes.

Möllmann H, Holzhey DM, Hilker M, Toggweiler S, ... Allocco DJ, Kim WK
Background
Transcatheter aortic valve implantation (TAVI) has become standard treatment for elderly patients with symptomatic severe aortic valve stenosis. The ACURATE neo AS study evaluates 30-day and 1-year clinical and hemodynamic outcomes in patients treated with the ACURATE neo2 valve.
Methods
The primary endpoint of this single-arm multicenter study is 30-day all-cause mortality. Other key endpoints include device performance, echocardiographic measures assessed by an independent core laboratory, and VARC-2 clinical efficacy and safety endpoints through 12 months.
Results
The study enrolled 120 patients (mean age 82.1 ± 4.0 years; 67.5% female, mean baseline STS score 4.8 ± 3.8%). The VARC-2 composite safety endpoint at 30 days occurred in 13.3% of patients. All-cause mortality was 3.3% at 30 days and 11.9% at 1 year. The 30-day stroke rate was 2.5% (disabling stroke 1.7%); there were no new strokes between 30 days and 12 months. The rate of permanent pacemaker implantation was 15.0% (18/120) at 30 days and 17.8% (21/120) at 1 year. No patients required re-intervention for valve-related dysfunction and there were no cases of valve thrombosis or endocarditis. Patients demonstrated significant improvement in mean aortic valve gradient (baseline 38.9 ± 13.1 mmHg, 1 year 7.8 ± 3.5 mmHg; P < 0.001 in a paired analysis). In the overall population, paravalvular leak was evaluated at 1 year as none/trace in 60.5%, mild in 37.0%, and moderate in 2.5%; no patients had severe PVL.
Conclusions
One-year outcomes from the ACURATE neo AS study support the safety and performance of TAVI with the ACURATE neo2 valve.



Clin Res Cardiol: 19 Jun 2021; epub ahead of print
Möllmann H, Holzhey DM, Hilker M, Toggweiler S, ... Allocco DJ, Kim WK
Clin Res Cardiol: 19 Jun 2021; epub ahead of print | PMID: 34148125
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Impact:
Abstract

New-onset atrial fibrillation in patients with worsening heart failure and coronary artery disease: an analysis from the COMMANDER-HF trial.

Ferreira JP, Cleland JG, Lam CSP, Anker SD, ... Greenberg B, Zannad F
Background
Atrial fibrillation (AF) in the presence of heart failure (HF) is associated with poor outcomes including a high-risk of stroke and other thromboembolic events. Identifying patients without AF who are at high-risk of developing this arrhythmia has important clinical implications.
Aims
To develop a risk score to identify HF patients at high risk of developing AF.
Methods
The COMMANDER-HF trial enrolled 5022 patients with HF and a LVEF ≤ 40%, history of coronary artery disease, and absence of AF at baseline (confirmed with an electrocardiogram). Patients were randomized to either rivaroxaban (2.5 mg bid) or placebo. New-onset AF was confirmed by the investigator at study visits.
Results
241 (4.8%) patients developed AF during the follow-up (median 21 months). Older age (≥ 65 years), LVEF < 35%, history of PCI or CABG, White race, SBP < 110 mmHg, and higher BMI (≥ 25 kg/m2) were independently associated with risk of new-onset AF, whereas the use of DAPT was associated with a lower risk of new-onset AF. We then built a risk score from these variables (with good accuracy C-index = 0.71) and calibration across observed and predicted tertiles of risk. New-onset AF events rates increased steeply by increasing tertiles of the risk-score. Compared to tertile 1, the risk of new-onset AF was 2.5-fold higher in tertile 2, and 6.3-fold higher in tertile 3. Rivaroxaban had no effect in reducing new-onset AF. In time-updated models, new-onset AF was associated with a higher risk of subsequent all-cause death: HR (95%CI) 1.38 (1.11-1.73).
Conclusions
A well-calibrated risk-score identified patients at risk of new-onset AF in the COMMANDER-HF trial. Patients who developed AF had a higher risk of subsequent death. Risk of new-onset atrial fibrillation in patients with HFrEF and coronary artery disease.



Clin Res Cardiol: 13 Jun 2021; epub ahead of print
Ferreira JP, Cleland JG, Lam CSP, Anker SD, ... Greenberg B, Zannad F
Clin Res Cardiol: 13 Jun 2021; epub ahead of print | PMID: 34128083
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Impact:
Abstract

Exercise hemodynamics in heart failure patients with preserved and mid-range ejection fraction: key role of the right heart.

Rieth AJ, Richter MJ, Tello K, Gall H, ... Schulze PC, Hamm CW
Objective
We sought to explore whether classification of patients with heart failure and mid-range (HFmrEF) or preserved ejection fraction (HFpEF) according to their left ventricular ejection fraction (LVEF) identifies differences in their exercise hemodynamic profile, and whether classification according to an index of right ventricular (RV) function improves differentiation.
Background
Patients with HFmrEF and HFpEF have hemodynamic compromise on exertion. The classification according to LVEF implies a key role of the left ventricle. However, RV involvement in exercise limitation is increasingly recognized. The tricuspid annular plane systolic excursion/systolic pulmonary arterial pressure (TAPSE/PASP) ratio is an index of RV and pulmonary vascular function. Whether exercise hemodynamics differ more between HFmrEF and HFpEF than between TAPSE/PASP tertiles is unknown.
Methods
We analyzed 166 patients with HFpEF (LVEF ≥ 50%) or HFmrEF (LVEF 40-49%) who underwent basic diagnostics (laboratory testing, echocardiography at rest, and cardiopulmonary exercise testing [CPET]) and exercise with right heart catheterization. Hemodynamics were compared according to echocardiographic left ventricular or RV function.
Results
Exercise hemodynamics (e.g. pulmonary arterial wedge pressure/cardiac output [CO] slope, CO increase during exercise, and maximum total pulmonary resistance) showed no difference between HFpEF and HFmrEF, but significantly differed across TAPSE/PASP tertiles and were associated with CPET results. N-terminal pro-brain natriuretic peptide concentration also differed significantly across TAPSE/PASP tertiles but not between HFpEF and HFmrEF.
Conclusion
In patients with HFpEF or HFmrEF, TAPSE/PASP emerged as a more appropriate stratification parameter than LVEF to predict clinically relevant impairment of exercise hemodynamics. Stratification of exercise hemodynamics in patients with HFpEF or HFmrEF according to LVEF or TAPSE/PASP, showing significant distinctions only with the RV-based strategy. All data are shown as median [upper limit of interquartile range] and were calculated using the independent-samples Mann-Whitney U test or Kruskal-Wallis test. PVR pulmonary vascular resistance; max maximum level during exercise.



Clin Res Cardiol: 09 Jun 2021; epub ahead of print
Rieth AJ, Richter MJ, Tello K, Gall H, ... Schulze PC, Hamm CW
Clin Res Cardiol: 09 Jun 2021; epub ahead of print | PMID: 34110459
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Impact:
Abstract

Catheter ablation of supraventricular tachycardia in patients with and without structural heart disease: insights from the German ablation registry.

Eitel C, Ince H, Brachmann J, Kuck KH, ... Senges J, Tilz RR
Aim
To compare patient characteristics, safety and efficacy of catheter ablation of supraventricular tachycardia (SVT) in patients with and without structural heart disease (SHD) enrolled in the German ablation registry.
Methods and results
From January 2007 until January 2010, a total of 12,536 patients (37.2% with known SHD) were enrolled and followed for at least one year. Patients with SHD more often underwent ablation for atrial flutter (45.8% vs. 20.9%, p < 0.001), whereas patients without SHD more often underwent ablation for atrioventricular nodal reentrant tachycardia (30.2% vs. 11.8%, p < 0.001) or atrioventricular reentrant tachycardia (9.1% vs. 1.6%, p < 0.001). Atrial fibrillation catheter ablation procedures were performed in a similar proportion of patients with and without SHD (38.1% vs. 36.9%, p = 0.21). Overall, periprocedural success rate was high in both groups. Death, myocardial infarction or stroke occurred in 0.2% and 0.1% of patients with and without SHD (p = 0.066). Major non-fatal complications prior to discharge were rare and did not differ significantly between patients with and without SHD (0.5% vs. 0.4%, p = 0.34). Kaplan-Meier mortality estimate at 1 year demonstrated a significant mortality increase in patients with SHD (2.6% versus 0.7%; p < 0.001).
Conclusion
Patients with and without SHD undergoing SVT ablation exhibit similar success rates and low major complication rates, despite disadvantageous baseline characteristics in SHD patients. These data highlight the safety and efficacy of SVT ablation in patients with and without SHD. Nevertheless Kaplan-Meier mortality estimates at 1 year demonstrate a significant mortality increase in patients with SHD, highlighting the importance of treating the underlying condition and reliable anticoagulation if indicated.



Clin Res Cardiol: 08 Jun 2021; epub ahead of print
Eitel C, Ince H, Brachmann J, Kuck KH, ... Senges J, Tilz RR
Clin Res Cardiol: 08 Jun 2021; epub ahead of print | PMID: 34106323
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Impact:
Abstract

Development and external validation of prognostic models to predict sudden and pump-failure death in patients with HFrEF from PARADIGM-HF and ATMOSPHERE.

Shen L, Claggett BL, Jhund PS, Abraham WT, ... Solomon SD, McMurray JJV
Background
Sudden death (SD) and pump failure death (PFD) are the two leading causes of death in patients with heart failure and reduced ejection fraction (HFrEF).
Objective
Identifying patients at higher risk for mode-specific death would allow better targeting of individual patients for relevant device and other therapies.
Methods
We developed models in 7156 patients with HFrEF from the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF) trial, using Fine-Gray regressions counting other deaths as competing risks. The derived models were externally validated in the Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure (ATMOSPHERE) trial.
Results
NYHA class and NT-proBNP were independent predictors for both modes of death. The SD model additionally included male sex, Asian or Black race, prior CABG or PCI, cancer history, MI history, treatment with LCZ696 vs. enalapril, QRS duration and ECG left ventricular hypertrophy. While LVEF, ischemic etiology, systolic blood pressure, HF duration, ECG bundle branch block, and serum albumin, chloride and creatinine were included in the PFD model. Model discrimination was good for SD and excellent for PFD with Harrell\'s C of 0.67 and 0.78 after correction for optimism, respectively. The observed and predicted incidences were similar in each quartile of risk scores at 3 years in each model. The performance of both models remained robust in ATMOSPHERE.
Conclusion
We developed and validated models which separately predict SD and PFD in patients with HFrEF. These models may help clinicians and patients consider therapies targeted at these modes of death.
Trial registration number
PARADIGM-HF: ClinicalTrials.gov NCT01035255, ATMOSPHERE: ClinicalTrials.gov NCT00853658.



Clin Res Cardiol: 07 Jun 2021; epub ahead of print
Shen L, Claggett BL, Jhund PS, Abraham WT, ... Solomon SD, McMurray JJV
Clin Res Cardiol: 07 Jun 2021; epub ahead of print | PMID: 34101002
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Impact:
Abstract

Effects of face masks on performance and cardiorespiratory response in well-trained athletes.

Egger F, Blumenauer D, Fischer P, Venhorst A, ... Meyer T, Mahfoud F
Background
During the COVID-19 pandemic, compulsory masks became an integral part of outdoor sports such as jogging in crowded areas (e.g. city parks) as well as indoor sports in gyms and sports centers. This study, therefore, aimed to investigate the effects of medical face masks on performance and cardiorespiratory parameters in athletes.
Methods
In a randomized, cross-over design, 16 well-trained athletes (age 27 ± 7 years, peak oxygen consumption 56.2 ± 5.6 ml kg-1 min-1, maximum performance 5.1 ± 0.5 Watt kg-1) underwent three stepwise incremental exercise tests to exhaustion without mask (NM), with surgical mask (SM) and FFP2 mask (FFP2). Cardiorespiratory and metabolic responses were monitored by spiroergometry and blood lactate (BLa) testing throughout the tests.
Results
There was a large effect of masks on performance with a significant reduction of maximum performance with SM (355 ± 41 Watt) and FFP2 (364 ± 43 Watt) compared to NM (377 ± 40 Watt), respectively (p < 0.001; ηp2 = 0.50). A large interaction effect with a reduction of both oxygen consumption (p < 0.001; ηp2 = 0.34) and minute ventilation (p < 0.001; ηp2 = 0.39) was observed. At the termination of the test with SM 11 of 16 subjects reported acute dyspnea from the suction of the wet and deformed mask. No difference in performance was observed at the individual anaerobic threshold (p = 0.90).
Conclusion
Both SM and to a lesser extent FFP2 were associated with reduced maximum performance, minute ventilation, and oxygen consumption. For strenuous anaerobic exercise, an FFP2 mask may be preferred over an SM.



Clin Res Cardiol: 05 Jun 2021; epub ahead of print
Egger F, Blumenauer D, Fischer P, Venhorst A, ... Meyer T, Mahfoud F
Clin Res Cardiol: 05 Jun 2021; epub ahead of print | PMID: 34091726
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Impact:
Abstract

Left ventricular function recovery after ST-elevation myocardial infarction: correlates and outcomes.

Dauw J, Martens P, Deferm S, Bertrand P, ... Dupont M, Mullens W
Background
Contemporary data on left ventricular function (LVF) recovery in patients with left ventricular dysfunction after ST-elevation myocardial infarction (STEMI) are scarce and to date, no comparison has been made with patients with a baseline normal LVF. This study examined predictors of LVF recovery and its relation to outcomes in STEMI.
Methods
Patients presenting with STEMI between January 2010 and December 2016 were categorized in three groups after 3 months according to left ventricular ejection fraction (EF): (i) baseline normal LVF (EF ≥ 50% at baseline); (ii) recovered LVF (EF < 50% at baseline and ≥ 50% after 3 months); and (iii) reduced LVF (EF < 50% at baseline and after 3 months). Heart failure hospitalization, all-cause mortality and cardiovascular mortality were compared between the three groups.
Results
Of 577 patients, 341 (59%) patients had a baseline normal LVF, 112 (19%) had a recovered LVF and 124 (22%) had a reduced LVF. Independent correlates of LVF recovery were higher baseline EF, lower peak troponin and cardiac arrest. After median 5.8 years, there was no difference in outcomes between patients with LVF recovery and baseline normal LVF. In contrast, even after multivariate adjustment, patients with persistently reduced LVF had a higher risk for heart failure hospitalization (HR 5.00; 95% CI 2.17-11.46) and all-cause mortality (HR 1.87; 95% CI 1.11-3.16).
Conclusion
In contemporary treated STEMI patients, prognosis is significantly worse in those with a persistently reduced LVF after 3 months, compared with patients with a baseline normal LVF and those with LVF recovery.



Clin Res Cardiol: 04 Jun 2021; epub ahead of print
Dauw J, Martens P, Deferm S, Bertrand P, ... Dupont M, Mullens W
Clin Res Cardiol: 04 Jun 2021; epub ahead of print | PMID: 34091698
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Impact:
Abstract

Patients with acute myocarditis and preserved systolic left ventricular function: comparison of global and regional longitudinal strain imaging by echocardiography with quantification of late gadolinium enhancement by CMR.

Meindl C, Paulus M, Poschenrieder F, Zeman F, Maier LS, Debl K
Background
Conventional transthoracic echocardiography (TTE) does often not accurately reveal pathologies in patients with acute myocarditis and preserved left ventricular ejection fraction (LVEEF). Therefore, we investigated the diagnostic value of two-dimensional (2D) speckle tracking echocardiography compared to late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR) imaging in patients with acute myocarditis and normal global LVEF.
Methods and results
31 patients (group 1) with the diagnosis of acute myocarditis confirmed by CMR according to the Lake Louise criteria and 20 healthy controls (group 2) were analyzed including global longitudinal strain (GLS) and regional longitudinal strain (RLS) derived by the bull\'s eye plot. Although preserved LVEF was present in both groups, GLS was significantly lower in patients with acute myocarditis (group 1: GLS - 19.1 ± 1.8% vs. group 2: GLS - 22.1 ± 1.7%, p < 0.001). Compared to controls, lower RLS values were detected predominantly in the lateral, inferolateral, and inferior segments in patients with acute myocarditis. Additionally RLS values were significantly lower in segments without LGE.
Conclusion
In patients with acute myocarditis and preserved LVEF, a significant reduction of GLS compared to healthy subjects was detected. Further RLS adds important information to the localization and extent of myocardial injury.



Clin Res Cardiol: 03 Jun 2021; epub ahead of print
Meindl C, Paulus M, Poschenrieder F, Zeman F, Maier LS, Debl K
Clin Res Cardiol: 03 Jun 2021; epub ahead of print | PMID: 34086089
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Impact:
Abstract

Periinterventional inflammation and blood transfusions predict postprocedural delirium after percutaneous repair of mitral and tricuspid valves.

Körber MI, Schäfer M, Vimalathasan R, Mauri V, ... Baldus S, Pfister R
Objectives
The aim of this study was to examine predictors and impact of postoperative delirium (POD) on outcome after percutaneous repair of mitral and tricuspid valves.
Background
POD is common in elderly patients and contributes to increased health care costs and worse outcome. Predictors of POD in percutaneous mitral or tricuspid valve procedures are unclear.
Methods
In a prospective single-center study, patients were screened for POD using the Confusion Assessment Method on the first and second postprocedural days, and up until 7 days in patients with clinical suspicion of delirium. Associations of POD with baseline characteristics, periprocedural outcome and mid-term mortality were examined.
Results
One hundred and seventy-seven patients were included (median age 78 years [72-82], 41.8% female) and median (IQR) follow-up was 489 (293-704) days. Patients developing POD (n = 16, 9%) did not differ in baseline and procedural characteristics but more often received postinterventional blood transfusions (37.5% vs. 9.9%, p value = 0.007) and suffered from infections (43.8% vs. 9.9%, p value = 0.001). Patients with POD showed worse survival (HR: 2.71 [1.27-5.78]; p = 0.01), with an estimated 1-year survival of 46 ± 13% compared to 80 ± 3% in patients without POD (log-rank p value 0.007). In multivariate Cox regression, POD remained a significant predictor of mid-term mortality (HR 4.75 [1.97-11.5]; p = 0.001).
Conclusion
After percutaneous mitral or tricuspid valve repair, POD was independently associated with worse mid-term survival. Procedure- rather than patient-associated characteristics such as blood transfusions and infections emerged as important risk factors for development of POD. Considering the substantial prognostic impact of POD, further studies on its prevention are warranted to improve patient outcome.



Clin Res Cardiol: 31 May 2021; epub ahead of print
Körber MI, Schäfer M, Vimalathasan R, Mauri V, ... Baldus S, Pfister R
Clin Res Cardiol: 31 May 2021; epub ahead of print | PMID: 34061227
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Impact:
Abstract

Large extracellular vesicles in the left atrial appendage in patients with atrial fibrillation-the missing link?

Zietzer A, Al-Kassou B, Jamme P, Rolfes V, ... Nickenig G, Jansen F
Atrial fibrillation (AF) is the most frequent arrhythmic disease in humans, which leads to thrombus formation in the left atrial appendage and stroke through peripheral embolization. Depending on their origin, large extracellular vesicles (lEVs) can exert pro-coagulant functions. In the present study, we investigated how different types of AF influence the levels of large EV subtypes in three distinct atrial localizations. Blood samples were collected from the right and left atrium and the left atrial appendage of 58 patients. 49% of the patients had permanent AF, 34% had non-permanent AF, and 17% had no history of AF. Flow cytometric analysis of the origin of the lEVs showed that the proportion of platelet-derived lEVs in the left atrial appendage was significantly higher in permanent AF patients compared to non-permanent AF. When we grouped patients according to their current heart rhythm, we also detected significantly higher levels of platelet-derived lEVs in the left atrial appendage (LAA) in patients with atrial fibrillation. In vitro studies revealed, that platelet activation with lipopolysaccharide (LPS) leads to higher levels of miR-222-3p and miR-223-3p in platelet-derived lEVs. Treatment with lEVs from LPS- or thrombin-activated platelets reduces the migration of endothelial cells in vitro. These results suggest that permanent atrial fibrillation is associated with increased levels of platelet-derived lEVs in the LAA, which are potentially involved in LAA thrombus formation.



Clin Res Cardiol: 31 May 2021; epub ahead of print
Zietzer A, Al-Kassou B, Jamme P, Rolfes V, ... Nickenig G, Jansen F
Clin Res Cardiol: 31 May 2021; epub ahead of print | PMID: 34061226
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Impact:
Abstract

The INFluence of Remote monitoring on Anxiety/depRession, quality of lifE, and Device acceptance in ICD patients: a prospective, randomized, controlled, single-center trial.

Leppert F, Siebermair J, Wesemann U, Martens E, ... Kääb S, Wakili R
Background
Impact of telemedicine with remote patient monitoring (RPM) in implantable cardioverter-defibrillator (ICD) patients on clinical outcomes has been investigated in various clinical settings with divergent results. However, role of RPM on patient-reported-outcomes (PRO) is unclear. The INFRARED-ICD trial aimed to investigate the effect of RPM in addition to standard-of-care on PRO in a mixed ICD patient cohort.
Methods and results
Patients were randomized to RPM (n = 92) or standard in-office-FU (n = 88) serving as control group (CTL). At baseline and on a monthly basis over 1 year, study participants completed the EQ-5D questionnaire for the primary outcome Quality of Life (QoL), the Hospital Anxiety and Depression Scale, and the Florida Patient Acceptance Survey questionnaire for secondary outcomes. Demographic characteristics (82% men, mean age 62.3 years) and PRO at baseline were not different between RPM and CTL. Primary outcome analysis showed that additional RPM was not superior to CTL with respect to QoL over 12 months [+ 1.2 vs. + 3.9 points in CTL and RPM group, respectively (p = 0.24)]. Pre-specified analyses could not identify subgroups with improved QoL by the use of RPM. Neither levels of anxiety (- 0.4 vs. - 0.3, p = 0.88), depression (+ 0.3 vs. ± 0.0, p = 0.38), nor device acceptance (+ 1.1 vs. + 1.6, p = 0.20) were influenced by additional use of RPM.
Conclusion
The results of the present study show that PRO were not improved by RPM in addition to standard-of-care FU. Careful evaluation and planning of future trials in selected ICD patients are warranted before implementing RPM in routine practice.



Clin Res Cardiol: 30 May 2021; 110:789-800
Leppert F, Siebermair J, Wesemann U, Martens E, ... Kääb S, Wakili R
Clin Res Cardiol: 30 May 2021; 110:789-800 | PMID: 32417952
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Impact:
Abstract

Left-lateral thoracotomy for catheter ablation of scar-related ventricular tachycardia in patients with inaccessible pericardial access.

Zhang PP, Heeger CH, Mathew S, Fink T, ... Kuck KH, Ouyang F
Objectives
We aimed to describe the feasibility of a surgical left thoracotomy for catheter ablation of scar-related ventricular tachycardia (VT) in patients with inaccessible pericardial access.
Background
Pericardial adhesion due to prior cardiac surgery or previous epicardial ablation procedures limits epicardial access in patients with drug-refractory VT originated from the epicardium.
Methods
Six patients who underwent a surgical left lateral thoracotomy epicardial access for catheter ablation of VT after failed subxiphoid percutaneous epicardial access were reviewed. Patients\' baseline characteristics and procedural characteristics including epicardial access, mapping, and ablation were described. Epicardial access was successfully obtained in all patients by a surgical left lateral thoracotomy.
Results
The reasons of pericardial adhesion were prior cardiac surgery (n = 3, 50%) and previous epicardial ablation procedures (n = 3, 50%). Epicardial mapping of the lateral and inferior left ventricle was acquired, and a total of 15 different VTs originated from those regions were abolished. Unless one patient with ST elevation myocardial infarction due to periprocedural occlusion of the posterior descending artery no further complications occurred. All patients were discharged 10.2 ± 4 days after the procedure. VT recurred in 1 patient (17%) and was controlled with oral amiodarone therapy during follow-up (median follow-up: 479 days).
Conclusions
A surgical left lateral thoracotomy is feasible and safe for selected patients. This approach provides epicardial ablation in patients with VT located at the infero-lateral left ventricle and pericardial adhesions due to previous cardiac surgery or previous ablation procedures.



Clin Res Cardiol: 30 May 2021; 110:801-809
Zhang PP, Heeger CH, Mathew S, Fink T, ... Kuck KH, Ouyang F
Clin Res Cardiol: 30 May 2021; 110:801-809 | PMID: 32458110
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Impact:
Abstract

Anti-thrombotic strategies in patients with atrial fibrillation undergoing PCI.

Schäfer A, Flierl U, Bauersachs J
Triple anti-thrombotic therapy combining oral anticoagulation and dual anti-platelet therapy following percutaneous coronary intervention in patients with atrial fibrillation was considered as standard and recommended by guidelines. While bleeding risk is considerable with that approach, data for efficacy are scare. Several trials assessed the possibility of reducing anti-thrombotic treatment by mainly shortening the exposure to acetylsalicylic acid. Dropping one of the anti-platelet components might increase the risk of stent thrombosis, myocardial infarction or stroke. Despite that fear, the recent trials\' primary endpoint was major and/or clinically-relevant non-major bleeding. We review data on major bleedings, intracranial bleedings and major adverse cardiovascular events from the published reports. We demonstrate that Non-Vitamin K oral anticoagulant (NOAC)-based strategies compared to VKA-based triple therapies significantly reduce the risk for TIMI-major bleedings by 39% and for intracranial bleedings by 66%, while they did not increase the risk for overall ischemic or embolic events. However, recent meta-analyses indicate an increased risk for stent thrombosis with less intense anti-thrombotic therapy. While the overall incidence rate for stent thrombosis is rather low, relative increases by about 30-60% are reported, but they did not translate into adverse clinical net-benefit ratios. This review highlights that using certain NOAC regimens proven effective for stroke prevention in AF can reduce the rate of bleeding without increasing ischemic or embolic events. Furthermore, additive ASA in triple anti-thrombotic regimens should be limited to 1 month and individual weighing of ischemic versus bleeding risk during the first 30 days seems to be reasonable.



Clin Res Cardiol: 30 May 2021; 110:759-774
Schäfer A, Flierl U, Bauersachs J
Clin Res Cardiol: 30 May 2021; 110:759-774 | PMID: 32696081
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Impact:
Abstract

The impact of time-updated resting heart rate on cause-specific mortality in a random middle-aged male population: a lifetime follow-up.

Cui X, Mandalenakis Z, Thunström E, Fu M, Svärdsudd K, Hansson PO
Background
A high resting heart rate (RHR) is associated with an increase in adverse events. However, the long-term prognostic value in a general population is unclear. We aimed to investigate the impact of RHR, based on both baseline and time-updated values, on mortality in a middle-aged male cohort.
Methods
A random population sample of 852 men, all born in 1913, was followed from age 50 until age 98, with repeated examinations including RHR over a period of 48 years. The impact of baseline and time-updated RHR on cause-specific mortality was assessed using Cox proportional hazard models and cubic spline models.
Results
A baseline RHR of ≥ 90 beats per minute (bpm) was associated with higher all-cause mortality, as compared with an RHR of 60-70 bpm (hazard ratio [HR] 1.60, 95% confidence interval [CI] 1.17-2.19, P = 0.003), but not with cardiovascular (CV) mortality. A time-updated RHR of < 60 bpm (HR 1.41, 95% CI 1.07-1.85, P = 0.014) and a time-updated RHR of 70-80 bpm (HR 1.34, 95% CI 1.02-1.75, P = 0.036) were both associated with higher CV mortality as compared with an RHR of 60-70 bpm after multivariable adjustment. Analyses using cubic spline models confirmed that the association of time-updated RHR with all-cause and CV mortality complied with a U-shaped curve with 60 bpm as a reference.
Conclusion
In this middle-aged male cohort, a time-updated RHR of 60-70 bpm was associated with the lowest CV mortality, suggesting that a time-updated RHR could be a useful long-term prognostic index in the general population.



Clin Res Cardiol: 30 May 2021; 110:822-830
Cui X, Mandalenakis Z, Thunström E, Fu M, Svärdsudd K, Hansson PO
Clin Res Cardiol: 30 May 2021; 110:822-830 | PMID: 32696079
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Impact:
Abstract

Epicardial access for VT ablation: analysis of two different puncture techniques, incidence of adhesions and complication management.

Mathew S, Feickert S, Fink T, Rillig A, ... Kuck KH, Ouyang F
Introduction
Pericardial access for ablation of ventricular arrhythmias (VA) can be gained either by an anterior-oriented or inferior-oriented epicardial puncture under fluoroscopical guidance. We retrospectively sought to assess the safety of these two puncture techniques and the incidence of epicardial adhesions and introduce our algorithm for management of pericardial tamponade.
Methods and results
In 211 patients (61.4 ± 15.6 years, 179 males; 84.8%) 271 epicardial ablation procedures of VA were performed using either an anterior- or inferior-oriented approach for epicardial access. Puncture-related complications were systematically analyzed. Furthermore, the incidence of adhesions was evaluated during first and repeated procedures. A total of 34/271 (12.5%) major complications occurred and 23/271 (8.5%) were directly related to epicardial puncture. The incidence of puncture-related major complications in the anterior and inferior group was 4/82 (4.9%) and 19/189 (10.1%), respectively. Pericardial tamponade was the most common major complication (15/271; 5.5%). Collateral damages of adjacent structures such as liver, colon, gastric vessels and coronary arteries occurred in 6/189 (3.2%) patients and only within the inferior epicardial access group. Adhesions were documented in 19/211 (9%) patients during the first procedure and in 47.1% if patients had 2 or more procedures involving epicardial access.
Conclusion
Anterior-oriented epicardial puncture shows an observed association to a reduced incidence of pericardial tamponades and overall puncture-related complications in epicardial ablation of VA. In cases of repeated epicardial access adhesions increase significantly and may lead to ablation failure.



Clin Res Cardiol: 30 May 2021; 110:810-821
Mathew S, Feickert S, Fink T, Rillig A, ... Kuck KH, Ouyang F
Clin Res Cardiol: 30 May 2021; 110:810-821 | PMID: 32719917
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Impact:
Abstract

Pitfalls of the S-ICD therapy: experiences from a large tertiary centre.

Willy K, Reinke F, Rath B, Ellermann C, ... Eckardt L, Frommeyer G
Aim
The subcutaneous ICD (S-ICD) has evolved to a potential first option for many patients who have to be protected from sudden cardiac death. Many trials have underlined a similar performance regarding its effectiveness in relation to transvenous ICDs and have shown the expected benefits concerning infective endocarditis and lead failure. However, there have also been problems due to the peculiarities of the device, such as oversensing and myopotentials. In this study, we present patients from a large tertiary centre suffering from complications with an S-ICD and propose possible solutions.
Methods and results
All S-ICD patients who experienced complications related to the device (n = 40) of our large-scale single-centre S-ICD registry (n = 351 patients) were included in this study. Baseline characteristics, complications occurring and solutions to these problems were documented over a mean follow-up of 50 months. In most cases (n = 23), patients suffered from oversensing (18 cases with T wave or P wave oversensing, 5 due to myopotentials). Re-programming successfully prevented further oversensing episode in 13/23 patients. In 9 patients, generator or lead-related complications, mostly due to infectious reasons (5/9), occurred. Further problems consisted of ineffective shocks in one patient and need for antibradycardia stimulation in 2 patients and indication for CRT in 2 other patients. In total, the S-ICD had to be extracted in 10 patients. 7 of them received a tv-ICD subsequently, 3 patients refused re-implantation of any ICD. One other patient kept the ICD but had antitachycardic therapy deactivated due to inappropriate shocks for myopotential oversensing.
Conclusion
The S-ICD is a valuable option for many patients for the prevention of sudden cardiac death. Nonetheless, certain problems are immanent to the S-ICD (limited re-programming options, size of the generator) and should be addressed in future generations of the S-ICD.



Clin Res Cardiol: 30 May 2021; 110:861-867
Willy K, Reinke F, Rath B, Ellermann C, ... Eckardt L, Frommeyer G
Clin Res Cardiol: 30 May 2021; 110:861-867 | PMID: 33130912
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Impact:
Abstract

Safety and patient-reported outcomes in index ablation versus repeat ablation in atrial fibrillation: insights from the German Ablation Registry.

Kany S, Brachmann J, Lewalter T, Kuck KH, ... Metzner A, Rillig A
Background
Pulmonary vein isolation is an established strategy for catheter ablation of atrial fibrillation (AF). However, in a significant number of patients, a repeat procedure is mandatory due to arrhythmia recurrence. In this study, we report safety data and procedural details of patients undergoing index ablation versus repeat ablation in a registry-based real-life setting.
Methods
Patients from the German Ablation Registry, a prospective, multicentre registry of patients undergoing ablation between January 2007 and January 2010 were included.
Results
A total of 4155 patients were enrolled in the study. Group I (index ablation) consisted of 3377/4155 (82.1%) and group II (repeat ablation) of 738/4155 (17.9%). Patients in group I had a significantly higher ratio of paroxysmal AF (69.3% vs 61.9%, p < 0.001) and significantly less persistent AF (30.7% vs 38.1%, p < 0.001). The repeat group showed significantly lower mean RF application duration (2580 s. vs 1960, p < 0.001), less fluoroscopy time (29 min. vs. 27 min., p < 0.001), less mean dose area product (DAP) (3744 cGy × cm2 vs 3325 cGy × cm2, p = 0.001), and shorter study duration (181.2 min. vs 163.6 min., p < 0.001). No statistical difference between the groups was found in terms of mortality (0.3% vs 0.1%, p = 0.39), MACE (0.4% vs 0.3%, p = 0.58), MACCE (0.8% vs 0.6%, p = 0.47), composite safety endpoint (1.5% vs 1.4%, p = 0.76), and arrhythmia recurrence (43.8% vs 41.9%, p = 0.37) during 1-year follow-up. Both groups reported to have improved or no symptoms (80.4% vs 77.8%, p = 0.13).
Conclusion
Repeat catheter ablation is safe and provides a symptomatic relief comparable to index ablation. Repeat procedures are significantly shorter and use less fluoroscopy.



Clin Res Cardiol: 30 May 2021; 110:841-850
Kany S, Brachmann J, Lewalter T, Kuck KH, ... Metzner A, Rillig A
Clin Res Cardiol: 30 May 2021; 110:841-850 | PMID: 33112998
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Impact:
Abstract

Atrial fibrillation ablation strategies and technologies: past, present, and future.

Buist TJ, Zipes DP, Elvan A
Catheter ablation is an established treatment option for atrial fibrillation (AF), and pulmonary vein isolation (PVI) has become the gold standard in AF ablation. AF recurrence after PVI remains an important clinical problem. Recovery of conduction from the pulmonary veins (PVs) is considered the dominant mechanism for AF recurrence in paroxysmal AF. However, the underlying mechanism of AF recurrence after PVI is more complex in patients with persistent and longstanding persistent AF. Different ablation technologies and energy sources have been developed aimed at improving lesion quality and durability with an acceptable safety profile. Novel technologies are under evaluation which have a great potential to produce permanent PVI after a single ablation procedure. However, clinical value of these novel devices needs to be tested in adequately powered randomized controlled trials. In this article, we review the history of catheter ablation for AF and discuss the present and future ablation technologies.



Clin Res Cardiol: 30 May 2021; 110:775-788
Buist TJ, Zipes DP, Elvan A
Clin Res Cardiol: 30 May 2021; 110:775-788 | PMID: 33089361
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Impact:
Abstract

Clinical risk predictors in atrial fibrillation patients following successful coronary stenting: ENTRUST-AF PCI sub-analysis.

Goette A, Eckardt L, Valgimigli M, Lewalter T, ... Tijssen JG, Vranckx P
Aims
This subgroup analysis of the ENTRUST-AF PCI trial (ClinicalTrials.gov Identifier: NCT02866175; Date of registration: August 2016) evaluated type of AF, and CHA2DS2-VASc score parameters as predictors for clinical outcome.
Methods
Patients were randomly assigned after percutaneous coronary intervention (PCI) to either edoxaban (60 mg/30 mg once daily [OD]; n = 751) plus a P2Y12 inhibitor for 12 months or a vitamin K antagonist [VKA] (n = 755) plus a P2Y12 inhibitor and aspirin (100 mg OD, for 1-12 months). The primary outcome was a composite of major/clinically relevant non-major bleeding (CRNM) within 12 months. The composite efficacy endpoint consisted of cardiovascular death, stroke, systemic embolic events, myocardial infarction (MI), and definite stent thrombosis.
Results
Major/CRNM bleeding event rates were 20.7%/year and 25.6%/year with edoxaban and warfarin, respectively (HR [95% CI]: 0.83 [0.654-1.047]). The event rates of composite outcome were 7.26%/year and 6.86%/year, respectively (HR [95% CI]): 1.06 [0.711-1.587]), and of overall net clinical benefit were 12.48%/year and 12.80%/year, respectively (HR [(95% CI]: 0.99 [(0.730; 1.343]). Increasing CHA2DS2-VASc score was associated with increased rates of all outcomes. CHA2DS2-VASc score ≥ 5 was a marker for stent thrombosis. Paroxysmal AF was associated with a higher occurrence of MI (4.87% versus 2.01%, p = 0.0024).
Conclusion
After PCI in AF patients, increasing CHA2DS2-VASc score was associated with increased bleeding rates and CHA2DS2-VASc score (≥ 5) predicted the occurrence of stent thrombosis. Paroxysmal AF was associated with MI. These findings may have important clinical implications in AF patients.



Clin Res Cardiol: 30 May 2021; 110:831-840
Goette A, Eckardt L, Valgimigli M, Lewalter T, ... Tijssen JG, Vranckx P
Clin Res Cardiol: 30 May 2021; 110:831-840 | PMID: 33098470
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Impact:
Abstract

Sinus heart rate post pulmonary vein ablation and long-term risk of recurrences.

von Olshausen G, Saluveer O, Schwieler J, Drca N, ... Jensen-Urstad M, Braunschweig F
Purpose
Cather ablation is known to influence the autonomic nervous system. This study sought to investigate the association of sinus heart rate pre-/post-ablation and recurrences in patients with atrial fibrillation undergoing pulmonary vein isolation (PVI).
Methods
Between January 2012 and December 2017, data of 482 patients undergoing their first PVI were included. Sinus heart rate was recorded before (PRE), directly post-ablation (POST) and 3 months post-ablation (3 M). All patients were screened for atrial tachyarrhythmia recurrences during the one-year follow-up.
Results
In the total study cohort, the mean resting sinus heart rate at PRE [mean 57.9 bpm (95% CI 57.1-58.7 bpm)] increased by over 10 bpm to POST [mean 69.4 bpm (95% CI 68.5-70.3 bpm); p < 0.001] followed by a slight decrease at 3 M [mean 67.3 bpm (95% CI 66.4-68.2 bpm)] but still remaining higher compared to PRE (p < 0.001). This pattern was observed in patients with and without recurrences at POST and 3 M (both p < 0.001 compared to PRE). However, at 3 M the mean sinus heart rate was significantly lower in patients with compared to patients without recurrences (p = 0.031). In this regard, patients with a heart rate change < 11 bpm (PRE to 3 M) or, as an alternative parameter, patients with a heart rate < 60 bpm at 3 M had a significantly higher risk of recurrences compared to the remaining patients (Hazard ratio (HR) 1.82 (95% CI 1.32-2.49), p < 0.001 and HR 1.64 (95% CI 1.20-2.25), p = 0.002, respectively).
Conclusion
Our study confirms the impact of PVI on cardiac autonomic function with a significant sinus heart rate increase post-ablation. Patients with a sinus heart rate change < 11 bpm (PRE to 3 M) are at higher risk for recurrences during one-year post-PVI.



Clin Res Cardiol: 30 May 2021; 110:851-860
von Olshausen G, Saluveer O, Schwieler J, Drca N, ... Jensen-Urstad M, Braunschweig F
Clin Res Cardiol: 30 May 2021; 110:851-860 | PMID: 33184675
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Impact:
Abstract

Prospective multicentric validation of a novel prediction model for paroxysmal atrial fibrillation.

Schmidt C, Benda S, Kraft P, Wiedmann F, ... Katus HA, Kallenberger SM
Background
The early recognition of paroxysmal atrial fibrillation (pAF) is a major clinical challenge for preventing thromboembolic events. In this prospective and multicentric study we evaluated prediction scores for the presence of pAF, calculated from non-invasive medical history and echocardiographic parameters, in patients with unknown AF status.
Methods
The 12-parameter score with parameters age, LA diameter, aortic root diameter, LV,ESD, TDI A\', heart frequency, sleep apnea, hyperlipidemia, type II diabetes, smoker, ß-blocker, catheter ablation, and the 4-parameter score with parameters age, LA diameter, aortic root diameter and TDI A\' were tested. Presence of pAF was verified by continuous electrocardiogram (ECG) monitoring for up to 21 days in 305 patients.
Results
The 12-parameter score correctly predicted pAF in all 34 patients, in which pAF was newly detected by ECG monitoring. The 12- and 4-parameter scores showed sensitivities of 100% and 82% (95%-CI 65%, 93%), specificities of 75% (95%-CI 70%, 80%) and 67% (95%-CI 61%, 73%), and areas under the receiver operating characteristic (ROC) curves of 0.84 (95%-CI 0.80, 0.88) and 0.81 (95%-CI 0.74, 0.87). Furthermore, properties of AF episodes and durations of ECG monitoring necessary to detect pAF were analysed.
Conclusions
The prediction scores adequately detected pAF using variables readily available during routine cardiac assessment and echocardiography. The model scores, denoted as ECHO-AF scores, represent simple, highly sensitive and non-invasive tools for detecting pAF that can be easily implemented in the clinical practice and might serve as screening test to initiate further diagnostic investigations for validating the presence of pAF. Prospective validation of a novel prediction model for paroxysmal atrial fibrillation based on echocardiography and medical history parameters by long-term Holter ECG.



Clin Res Cardiol: 30 May 2021; 110:868-876
Schmidt C, Benda S, Kraft P, Wiedmann F, ... Katus HA, Kallenberger SM
Clin Res Cardiol: 30 May 2021; 110:868-876 | PMID: 33211156
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Impact:
Abstract

Predictors of response to cardiac resynchronization therapy in patients with chronic right ventricular pacing.

Rath B, Willy K, Wolfes J, Ellermann C, ... Eckardt L, Frommeyer G
Background
The benefits of de novo cardiac resynchronization therapy (CRT) in patients with QRS-prolongation and impaired left-ventricular function (LVEF) are well established. Current guidelines also recommend CRT-upgrade in patients requiring permanent or frequent right ventricular pacing (RVP) with symptomatic heart failure and reduced LVEF. Whereas several predictors of response to de novo CRT-implantation such as female gender, QRS-duration, non-ischemic cardiomyopathy (NICM) are known due to large prospective trials, similar factors regarding CRT-upgrade are currently lacking.
Methods and results
We examine 114 patients 3-6 months after CRT-upgrade due to frequent RVP (> 50%) and symptomatic heart failure. Response to CRT was evaluated by improvement in NYHA class referring to the Minnesota Living With Heart Failure Questionnaire. Only cardiomyopathy type and use of Angiotensin-converting-enzyme (ACE) inhibitor had an impact on response to CRT-upgrade in a linear regression model. Patients with NICM presented a greater responder rate than patients with ischemic cardiomyopathy (ICM) (80.4 vs. 60.3%, p < 0.05). Other traditional response predictors in de novo CRT recipients (e.g. QRS-width, female gender) showed no effect on CRT-response in this cohort.
Conclusion
Only underlying heart disease (NICM vs. ICM) and the use of ACE inhibitor were significant predictors of response to CRT-upgrade. In contrast to de novo CRT-recipients, where pre-implant QRS-duration is a key predictor, QRS-duration during RV-pacing has no significant impact on CRT-response in this cohort.



Clin Res Cardiol: 30 May 2021; 110:877-883
Rath B, Willy K, Wolfes J, Ellermann C, ... Eckardt L, Frommeyer G
Clin Res Cardiol: 30 May 2021; 110:877-883 | PMID: 33320290
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Impact:
Abstract

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

Riesenhuber M, Spannbauer A, Gwechenberger M, Pezawas T, ... Hengstenberg C, Gyongyosi M
Background
Transcatheter tricuspid valve intervention became an option for pacemaker lead-associated tricuspid regurgitation. This study investigated the progression of tricuspid regurgitation (TR) in patients with or without pre-existing right ventricular dilatation (RVD) undergoing pacemaker implantation.
Methods
Patients were included if they had implantation of transtricuspid pacemaker lead and completed echocardiography before and after implantation. The cohort was divided in patients with and without RVD (cut-off basal RV diameter ≥ 42 mm). TR was graded in none/mild, moderate, and severe. Worsening of one grade was defined as progression. Survival analyses were plotted for 10 years.
Results
In total, 990 patients were analyzed (24.5% with RVD). Progression of TR occurred in 46.1% of patients with RVD and in 25.6% of patients without RVD (P < 0.001). Predictors for TR progression were RV dilatation (OR 2.04; 95% CI 1.27-3.29; P = 0.003), pre-existing TR (OR 4.30; 95% CI 2.51-7.38; P < 0.001), female sex (OR 1.68; 95% CI 1.16-2.43; P = 0.006), single RV lead (OR 1.67; 95% CI 1.09-2.56; P = 0.018), mitral regurgitation (OR 2.08; 95% CI 1.42-3.05; P < 0.001), and enlarged left atrium (OR 1.98; 95% CI 1.07-3.67; P = 0.03). Survival-predictors were pacemaker lead-associated TR (HR 1.38; 95% CI 1.04-1.84; P = 0.028), mitral regurgitation (HR 1.34; 95% CI 1.02-1.77; P = 0.034), heart failure (HR 1.75; 95% CI 1.31-2.33; P < 0.001), kidney disease (HR 1.62; 95% CI 1.25-2.11; P < 0.001), and age ≥ 80 years (HR 2.84; 95% CI 2.17-3.71; P < 0.001).
Conclusions
Patients with RVD receiving pacemaker suffered from increased TR progression, leading to decreased survival.



Clin Res Cardiol: 30 May 2021; 110:884-894
Riesenhuber M, Spannbauer A, Gwechenberger M, Pezawas T, ... Hengstenberg C, Gyongyosi M
Clin Res Cardiol: 30 May 2021; 110:884-894 | PMID: 33566185
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Impact:
Abstract

Analysis of causes of death in patients with implanted defibrillators.

Nägele H, Gröene E, Stierle D, Nägele MP
Aims
Implantable cardioverter defibrillators (ICDs) are used for primary or secondary prevention of sudden cardiac death. We sought to clarify prognosis and causes of death after ICD implantation.
Methods and results
A total of 2743 patients with ICDs implanted during 1990-2020 were analyzed. Median age was 68.5 (59.6-74.6) years; 21% women, median left ventricular ejection fraction (LVEF) was 30 (23-35), 52% had an ischemic etiology and 77% had a primary preventive indication. Mortality rate after 10 years was 22, 44, 55, and 72% in the 1st, 2nd, 3rd, and 4th age quartile, respectively. The calculated median sex and age adjusted loss of life years compared to the average German population was 9.7 (6.1-14.0) years. Prognosis was independently related to sex, age, LVEF, and glomerular filtration rate. 713 out of 852 deaths could be classified to a specific cause. Congestive heart failure (CHF) accounted for death in 214 (30%) and sudden death (SD) for 144 patients (20%). Postmortem interrogation of devices in 74 patients revealed VT/VF in 39 and no episodes in 35 patients. Cancer was identified as the cause of death in 121 patients (17% of cases), of which 36 were bronchial carcinomas. 73 (10%) of patients died due to infection. 67 patients (9%) died within 24 h of procedures. Compared to other causes, significantly more life years were lost associated with procedures and SD: 9.3 (5.7-12.9) versus 12.1 (7.4-15.2) and 11.9 (7.6-17.8) years.
Conclusion
Life expectancy of ICD patients is lower than for the general population. Mortality is predominantly due to CHF, but there is still a considerable rate of SD. The occurrence of cancers, most importantly bronchial carcinomas, and infections, warrants protective measures. Some deaths during procedures are possibly preventable. Patients with ICDs comprise a vulnerable cohort, and treatment has to be optimized in many directions to improve prognosis.



Clin Res Cardiol: 30 May 2021; 110:895-904
Nägele H, Gröene E, Stierle D, Nägele MP
Clin Res Cardiol: 30 May 2021; 110:895-904 | PMID: 33687520
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Impact:
Abstract

Prospective blinded evaluation of smartphone-based ECG for differentiation of supraventricular tachycardia from inappropriate sinus tachycardia.

Wegner FK, Kochhäuser S, Frommeyer G, Lange PS, ... Eckardt L, Dechering DG
Introduction
Supraventricular tachycardias (SVT) are often difficult to document due to their intermittent, short-lasting nature. Smartphone-based one-lead ECG monitors (sECG) were initially developed for the diagnosis of atrial fibrillation. No data have been published regarding their potential role in differentiating inappropiate sinus tachycardia (IST) from regular SVT. If cardiologists could distinguish IST from SVT in sECG, economic health care burden might be significantly reduced.
Methods
We prospectively recruited 75 consecutive patients with known SVT undergoing an EP study. In all patients, four ECG were recorded: a sECG during SVT and during sinus tachycardia and respective 12-lead ECG. Two experienced electrophysiologists were blinded to the diagnoses and separately evaluated all ECG.
Results
Three hundred individual ECG were recorded in 75 patients (47 female, age 50 ± 18 years, BMI 26 ± 5 kg/m2, 60 AVNRT, 15 AVRT). The electrophysiologists\' blinded interpretation of sECG recordings showed a sensitivity of 89% and a specificity of 91% for the detection of SVT (interobserver agreement κ = 0.76). In high-quality sECG recordings (68%), sensitivity rose to 95% with a specificity of 92% (interobserver agreement of κ = 0.91). Specificity increased to 96% when both electrophysiologists agreed on the diagnosis. Respective 12-lead ECG had a sensitivity of 100% and specificity of 98% for the detection of SVT.
Conclusion
A smartphone-based one-lead ECG monitor allows for differentiation of SVT from IST in about 90% of cases. These results should encourage cardiologists to integrate wearables into clinical practice, possibly reducing time to definitive diagnosis of an arrhythmia and unnecessary EP procedures. A smartphone-based one lead ECG device (panel A) can be used reliably to differentiate supraventricular tachycardia (panel B) from inappropriate sinus tachycardia when compared to a simultaneously conducted gold-standard electrophysiology study (panels C, D).



Clin Res Cardiol: 30 May 2021; 110:905-912
Wegner FK, Kochhäuser S, Frommeyer G, Lange PS, ... Eckardt L, Dechering DG
Clin Res Cardiol: 30 May 2021; 110:905-912 | PMID: 33961097
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Impact:
Abstract

Associations between kidney function and outcomes of comprehensive cardiac rehabilitation in patients with heart failure.

Hamazaki N, Kamiya K, Yamamoto S, Nozaki K, ... Matsunaga A, Ako J
Aims
To investigate the impact of baseline kidney function on outcomes following comprehensive cardiac rehabilitation (CR) in patients with heart failure (HF).
Methods
We reviewed a total of 3,727 patients who were admitted for HF treatment. Estimated glomerular filtration rate (eGFR), quadriceps strength (QS), and 6-min walk distance (6MWD) were measured at hospital discharge as a baseline and 5 months thereafter in participants of outpatient comprehensive CR. The association between outpatient CR participation and all-cause events was evaluated using propensity score-matched analysis in subgroups across eGFR stages. The changes in QS and 6MWD following 5-month CR were compared between eGFR stages.
Results
Out of the studied patients, 1585 (42.5%) participated in outpatient CR. After propensity matching for clinical confounders, 2680 patients were included for analysis (pairs of n = 1340 outpatient CR participants and nonparticipants). The participation in outpatient CR was significantly associated with low clinical events in subgroups of eGFR ≥ 60 [hazard ratio (HR): 0.65, 95% confidence interval (CI): 0.51-0.84] and eGFR 45-60 (HR: 0.71, 95% CI: 0.55-0.92), but not in eGFR 30-45 (HR: 0.83, 95% CI: 0.64-1.08) and eGFR < 30 (HR: 0.88, 95% CI: 0.69-1.12). QS and 6MWD were significantly higher after 5-month CR than those at baseline (P < 0.001, respectively), but lower baseline eGFR correlated with lower changes in QS and 6MWD (trend P < 0.001, respectively).
Conclusions
Although low baseline kidney function attenuates the outcomes of CR, outpatient CR seems to be associated with a better prognosis and positive change in physical function in HF patients with low kidney function.



Clin Res Cardiol: 30 May 2021; epub ahead of print
Hamazaki N, Kamiya K, Yamamoto S, Nozaki K, ... Matsunaga A, Ako J
Clin Res Cardiol: 30 May 2021; epub ahead of print | PMID: 34057614
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Impact:
Abstract

Hypertrophic cardiomyopathies requiring more monitoring for less atrial fibrillation-related complications: a clustering analysis based on the French registry on hypertrophic cardiomyopathy (REMY).

Hourqueig M, Bouzille G, Mirabel M, Huttin O, ... Donal E, REMY working group of the French Society of Cardiology
Aims
Defining the risk of atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) patients is an important clinical and prognostic challenge. The aim of this study is to determine HCM phenogroups with different risk of AF occurrence at 5 years.
Methods and results
We applied retrospectively the Bayesian method, which can analyze a large number of variables, to differentiate phenogroups of patients with different risks of AF and prognoses across a French prospective on-going hospital-based registry of adult HCM patients (REMY). Clinical and imaging data were prospectively recorded, and patients were followed for 5 years. A total of 1431 HCM patients were recruited, including 1275 analyzed in the present study after exclusion criteria. The population included 412 women, 369 patients with obstructive HCM, and 252 implanted with an ICD. AF occurred in 167 (11.6%) patients during the 5 year follow-up. Three phenogroups were defined according to their common clinical and echocardiographic characteristics. Patients at the highest risk were oldest, more often female, with more frequent comorbidities, anteroposterior diameter of the left atrium was significantly greater, with diastolic dysfunction, outflow-tract obstruction, and mitral valve abnormality, and presented higher pulmonary artery pressure and/or right-ventricular dysfunction. These also had a higher risk of all-cause hospitalizations and death.
Conclusion
Based on a clustering analysis, three phenogroups of HCM according to the risk of AF occurrence can be identified. It can indicate which patients should be more monitored and/or treated, particular to prevent the risk of stroke.



Clin Res Cardiol: 26 May 2021; epub ahead of print
Hourqueig M, Bouzille G, Mirabel M, Huttin O, ... Donal E, REMY working group of the French Society of Cardiology
Clin Res Cardiol: 26 May 2021; epub ahead of print | PMID: 34043053
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Impact:
Abstract

Impact of atrial fibrillation pattern on outcomes after left atrial appendage closure: lessons from the prospective LAARGE registry.

Kany S, Brachmann J, Lewalter T, Akin I, ... Kirchhof P, Rillig A
Background
Non-paroxysmal (NPAF) forms of atrial fibrillation (AF) have been reported to be associated with an increased risk for systemic embolism or death.
Methods
Comparison of procedural details and long-term outcomes in patients (pts) with paroxysmal AF (PAF) against controls with NPAF in the prospective, multicentre observational registry of patients undergoing LAAC (LAARGE).
Results
A total of 638 pts (PAF 274 pts, NPAF 364 pts) were enrolled. In both groups, a history of PVI was rare (4.0% vs 1.6%, p = 0.066). The total CHA2DS2-VASc score was lower in the PAF group (4.4 ± 1.5 vs 4.6 ± 1.5, p = 0.033), while HAS-BLED score (3.8 ± 1.1 vs 3.9 ± 1.1, p = 0.40) was comparable. The rate of successful implantation was equally high (97.4% vs 97.8%, p = 0.77). In the three-month echo follow-up, LA thrombi (2.1% vs 7.3%, p = 0.12) and peridevice leak > 5 mm (0.0% vs 7.1%, p = 0.53) were numerically higher in the NPAF group. Overall, in-hospital complications occurred in 15.0% of the PAF cohort and 10.7% of the NPAF cohort (p = 0.12). In the one-year follow-up, unadjusted mortality (8.4% vs 14.0%, p = 0.039) and combined outcome of death, stroke and systemic embolism (8.8% vs 15.1%, p = 0.022) were significantly higher in the NPAF cohort. After adjusting for CHA2DS2-VASc and previous bleeding, NPAF was associated with increased death/stroke/systemic embolism (HR 1.67, 95% CI 1.02-2.72, p = 0.041).
Conclusion
Atrial fibrillation type did not impair periprocedural safety or in-hospital MACE patients undergoing LAAC. However, after one year, NPAF was associated with higher mortality.



Clin Res Cardiol: 26 May 2021; epub ahead of print
Kany S, Brachmann J, Lewalter T, Akin I, ... Kirchhof P, Rillig A
Clin Res Cardiol: 26 May 2021; epub ahead of print | PMID: 34043052
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Impact:
Abstract

Sex-specific differences and long-term outcome of patients with coronary artery disease and chronic kidney disease: the Coronary Artery Disease and Renal Failure (CAD-REF) Registry.

Engelbertz C, Pinnschmidt HO, Freisinger E, Reinecke H, ... Pavenstädt H, Brand E
Background
Cardiovascular morbidity and mortality are closely linked to chronic kidney disease (CKD). Sex-specific long-term outcome data of patients with coronary artery disease (CAD) and CKD are scarce.
Methods
In the prospective observational multicenter Coronary Artery Disease and REnal Failure (CAD-REF) Registry, 773 (23.1%) women and 2,579 (76.9%) men with angiographically documented CAD and different stages of CKD were consecutively enrolled and followed for up to 8 years. Long-term outcome was evaluated using survival analysis and multivariable Cox-regression models.
Results
At enrollment, women were significantly older than men, and suffered from more comorbidities like CKD, hypertension, diabetes mellitus, and multivessel coronary disease. Regarding long-term mortality, no sex-specific differences were observed (Kaplan-Meier survival estimates: 69% in women vs. 69% in men, plog-rank = 0.7). Survival rates decreased from 89% for patients without CKD at enrollment to 72% for patients with CKD stages 1-2 at enrollment and 49% for patients with CKD stages 3-5 at enrollment (plog-rank < 0.001). Cox-regression analysis revealed that sex or multivessel coronary disease were no independent predictors of long-term mortality, while age, CKD stages 3-5, albumin/creatinine ratio, diabetes, valvular heart disease, peripheral artery disease, and left-ventricular ejection fraction were predictors of long-term mortality.
Conclusions
Sex differences in CAD patients mainly exist in the cardiovascular risk profile and the extent of CAD. Long-term mortality was not depended on sex or multivessel disease. More attention should be given to treatment of comorbidities such as CKD and peripheral artery disease being independent predictors of death. Clinical Trail Registration ClinicalTrials.gov Identifier: NCT00679419.



Clin Res Cardiol: 25 May 2021; epub ahead of print
Engelbertz C, Pinnschmidt HO, Freisinger E, Reinecke H, ... Pavenstädt H, Brand E
Clin Res Cardiol: 25 May 2021; epub ahead of print | PMID: 34036426
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Impact:
Abstract

Ethnic comparison in takotsubo syndrome: novel insights from the International Takotsubo Registry.

Imori Y, Kato K, Cammann VL, Szawan KA, ... Ghadri JR, Templin C
Background
Ethnic disparities have been reported in cardiovascular disease. However, ethnic disparities in takotsubo syndrome (TTS) remain elusive. This study assessed differences in clinical characteristics between Japanese and European TTS patients and determined the impact of ethnicity on in-hospital outcomes.
Methods
TTS patients in Japan were enrolled from 10 hospitals and TTS patients in Europe were enrolled from 32 hospitals participating in the International Takotsubo Registry. Clinical characteristics and in-hospital outcomes were compared between Japanese and European patients.
Results
A total of 503 Japanese and 1670 European patients were included. Japanese patients were older (72.6 ± 11.4 years vs. 68.0 ± 12.0 years; p < 0.001) and more likely to be male (18.5 vs. 8.4%; p < 0.001) than European TTS patients. Physical triggering factors were more common (45.5 vs. 32.0%; p < 0.001), and emotional triggers less common (17.5 vs. 31.5%; p < 0.001), in Japanese patients than in European patients. Japanese patients were more likely to experience cardiogenic shock during the acute phase (15.5 vs. 9.0%; p < 0.001) and had a higher in-hospital mortality (8.2 vs. 3.2%; p < 0.001). However, ethnicity itself did not appear to have an impact on in-hospital mortality. Machine learning approach revealed that the presence of physical stressors was the most important prognostic factor in both Japanese and European TTS patients.
Conclusion
Differences in clinical characteristics and in-hospital outcomes between Japanese and European TTS patients exist. Ethnicity does not impact the outcome in TTS patients. The worse in-hospital outcome in Japanese patients, is mainly driven by the higher prevalence of physical triggers.
Trial registration
URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT01947621.



Clin Res Cardiol: 18 May 2021; epub ahead of print
Imori Y, Kato K, Cammann VL, Szawan KA, ... Ghadri JR, Templin C
Clin Res Cardiol: 18 May 2021; epub ahead of print | PMID: 34013386
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Impact:
Abstract

Clopidogrel vs. prasugrel vs. ticagrelor in patients with acute myocardial infarction complicated by cardiogenic shock: a pooled IABP-SHOCK II and CULPRIT-SHOCK trial sub-analysis.

Orban M, Kleeberger J, Ouarrak T, Freund A, ... Thiele H, Hausleiter J
Aims
The aim of this pooled sub-analysis of the Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) and Culprit Lesion Only PCI versus Multivessel PCI in Cardiogenic Shock (CULPRIT-SHOCK) trial was to compare the clinical outcome of patients with acute myocardial infarction complicated by cardiogenic shock treated either with clopidogrel or the newer, more potent ADP-receptor antagonists prasugrel or ticagrelor.
Methods and results
For the current analysis the primary endpoint was 1-year mortality and the secondary safety endpoint was moderate or severe bleedings until hospital discharge with respect to three different ADP-receptor antagonists. 856 patients were eligible for analysis. Of these, 507 patients (59.2%) received clopidogrel, 178 patients (20.8%) prasugrel and 171 patients (20.0%) ticagrelor as acute antiplatelet therapy. The adjusted rate of mortality after 1-year did not differ significantly between prasugrel and clopidogrel (hazard ratio [HR]: 0.81, 95% confidence interval [CI] 0.60-1.09, padj = 0.17) or between ticagrelor and clopidogrel treated patients (HR: 0.86, 95% CI 0.65-1.15, padj = 0.31). In-hospital bleeding events were significantly less frequent in patients treated with ticagrelor vs. clopidogrel (HR: 0.37, 95% CI 0.20 -0.69, padj = 0.002) and not significantly different in patients treated with prasugrel vs. clopidogrel (HR: 0.73, 95% CI 0.43 -1.24, padj = 0.24).
Conclusion
This pooled sub-analysis is the largest analysis on safety and efficacy of three oral ADP-receptor antagonists and shows that acute therapy with either clopidogrel, prasugrel or ticagrelor is no independent predictor of 1-year mortality. Treatment with ticagrelor seems independently associated with less in-hospital moderate and severe bleeding events compared to clopidogrel. This finding might be due to selection bias and should be interpreted with caution.



Clin Res Cardiol: 16 May 2021; epub ahead of print
Orban M, Kleeberger J, Ouarrak T, Freund A, ... Thiele H, Hausleiter J
Clin Res Cardiol: 16 May 2021; epub ahead of print | PMID: 33999281
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Impact:
Abstract

Timely and individualized heart failure management: need for implementation into the new guidelines.

Abdin A, Bauersachs J, Frey N, Kindermann I, ... Wintrich J, Böhm M
Due to remarkable improvements in heart failure (HF) management over the last 30 years, a significant reduction in mortality and hospitalization rates in HF patients with reduced ejection fraction (HFrEF) has been observed. Currently, the optimization of guideline-directed chronic HF therapy remains the mainstay to further improve outcomes for patients with HFrEF to reduce mortality and HF hospitalization. This includes established device therapies, such as implantable defibrillators and cardiac resynchronization therapies, which improved patients\' symptoms and prognosis. Over the last 10 years, new HF drugs have merged targeting various pathways, such as those that simultaneously suppress the renin-angiotensin-aldosterone system and the breakdown of endogenous natriuretic peptides (e.g., sacubitril/valsartan), and those that inhibit the If channel and, thus, reduce heart rate (e.g., ivabradine). Furthermore, the treatment of patient comorbidities (e.g., iron deficiency) has shown to improve functional capacity and to reduce hospitalization rates, when added to standard therapy. More recently, other potential treatment mechanisms have been explored, such as the sodium/glucose co-transporter inhibitors, the guanylate cyclase stimulators and the cardiac myosin activators. In this review, we summarize the novel developments in HFrEF pharmacological and device therapy and discuss their implementation strategies into practice to further improve outcomes.



Clin Res Cardiol: 12 May 2021; epub ahead of print
Abdin A, Bauersachs J, Frey N, Kindermann I, ... Wintrich J, Böhm M
Clin Res Cardiol: 12 May 2021; epub ahead of print | PMID: 33983472
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Impact:
Abstract

Development of a novel CT-derived measure of cardiovascular health: the CT aortic stiffness index (CTASI).

Broyd CJ, Pugliese F, Patel K, Bedford K, ... Kennon S, Mullen M
Aims
Aortic stiffness, measured as aortic pulse wave velocity (PWV), is a powerful predictor of cardiovascular health but is difficult to accurately obtain non-invasively. This study sought to develop a novel CT aortic stiffness index (CTASI) which incorporates both anatomical (calcification) and physiological (distensibility) aspects of aortic health.
Methods
Invasive PWV and CT scans were obtained for 80 patients undergoing TAVI (cohort 1). CT data alone were obtained from an additional 238 patients (cohort 2). Aortic calcification was quantified using a modified Agatston\'s methodology. Distensibility-PWV was calculated from minimum and maximum ascending aorta areas. Linear regression of these values was used to construct CTASI from cohort 1. CTASI was then calculated for cohort 2 who were prospectively followed-up.
Results
CTASI correlated with invasive PWV (rho = 0.47, p < 0.01) with a higher correlation coefficient than distensibility-PWV (rho = 0.35, p < 0.01) and aortic calcification (rho = 0.36, p < 0.01). Compared to invasive PWV, CTASI had a good accuracy as a diagnostic test (AOC 0.72 [95% CI 0.61-0.84]), superior to aortic calcification and distensibility-PWV alone (χ2 = 0.82, p = 0.02). There were 61 deaths during a median follow-up of 771 days (95% CI 751.4-790.5). CTASI was able to predict 1-year mortality (OR 2.58, 95% CI 1.18-5.61, p = 0.02) and Kaplan-Meier survival (log-rank p = 0.03).
Conclusion
CTASI is a stronger measure of aortic stiffness than aortic calcification or distensibility alone. Given the prolific use of CT scanning for assessing coronary and vascular disease, the additional calculation of CTASI during these scans could provide an important direct measurement of vascular health and guide pharmacological therapy.



Clin Res Cardiol: 11 May 2021; epub ahead of print
Broyd CJ, Pugliese F, Patel K, Bedford K, ... Kennon S, Mullen M
Clin Res Cardiol: 11 May 2021; epub ahead of print | PMID: 33978816
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Impact:
Abstract

The impact of epicardial adipose tissue in patients with acute myocardial infarction.

Fisser C, Colling S, Debl K, Hetzenecker A, ... Buchner S, Arzt M
Aims
Epicardial adipose tissue (EAT) has been linked to impaired reperfusion success after percutaneous coronary intervention (PCI). Whether EAT predicts myocardial damage in the early phase after acute myocardial infarction (MI) is unclear. Therefore, we investigated whether EAT in patients with acute MI is associated with more microvascular obstruction (MVO), greater ST-deviation, larger infarct size and reduced myocardial salvage index (MSI).
Methods and results
This retrospective analysis of a prospective observational study including patients with acute MI (n = 54) undergoing PCI and 12 healthy matched controls. EAT, infarct size and MSI were analyzed with cardiac magnetic resonance imaging, conducted 3-5 days and 12 weeks after MI. Patients with acute MI showed higher EAT volume than healthy controls (46 [25.;75. percentile: 37;59] vs. 24 [15;29] ml, p < 0.001). The high EAT group (above median) showed significantly more MVO (2.22 [0.00;5.38] vs. 0.0 [0.00;2.18] %, p = 0.004), greater ST-deviation (0.38 [0.22;0.55] vs. 0.15 [0.03;0.20] mV×10-1, p = 0.008), larger infarct size at 12 weeks (23 [17;29] vs. 10 [4;16] %, p < 0.001) and lower MSI (40 [37;54] vs. 66 [49;88] %, p < 0.001) after PCI than the low EAT group. After accounting for demographic characteristics, body-mass index, heart volume, infarct location, TIMI-flow grade as well as apnea-hypopnea index, EAT was associated with infarct size at 12 weeks (B = 0.38 [0.11;0.64], p = 0.006), but not with MSI.
Conclusions
Patients with acute MI showed higher volume of EAT than healthy individuals. High EAT was linked to more MVO and greater ST-deviation. EAT was associated with infarct size, but not with MSI.



Clin Res Cardiol: 11 May 2021; epub ahead of print
Fisser C, Colling S, Debl K, Hetzenecker A, ... Buchner S, Arzt M
Clin Res Cardiol: 11 May 2021; epub ahead of print | PMID: 33978815
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Impact:
Abstract

New challenges in cardiac intensive care units.

Lüsebrink E, Kellnar A, Scherer C, Krieg K, ... Massberg S, Orban M
Critical care cardiology is a steadily and rapidly developing sub-specialization within cardiovascular medicine, since the first emergence of a coronary care unit in the early 1960s. Today, modern cardiac intensive care units (CICU) serve a complex patient population with a high burden of cardiovascular and non-cardiovascular critical illnesses. Treatment of these patients requires a multidisciplinary approach, with a combination of highly specialized knowledge and skills in cardiovascular diseases, as well as emergency, critical-care and internal medicine. The CICU has always posed special challenges to both experienced intensivists as well as fellows-in-training (FIT) and is certainly one of the most demanding training phases. In recent years, these challenges have grown significantly owing to technological innovations, with new and steadily rising numbers of complex interventional procedures and new options for temporary circulatory support for critically ill patients, such as venoarterial extracorporeal membrane oxygenation (VA-ECMO). Herein, we focus on the successful CICU management of these special patient cohorts, which must become an integral part of critical-care training.



Clin Res Cardiol: 08 May 2021; epub ahead of print
Lüsebrink E, Kellnar A, Scherer C, Krieg K, ... Massberg S, Orban M
Clin Res Cardiol: 08 May 2021; epub ahead of print | PMID: 33966127
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Impact:
Abstract

Diuretic therapy as prognostic enrichment factor for clinical trials in patients with heart failure with reduced ejection fraction.

Coiro S, Girerd N, McMurray JJV, Pitt B, ... Rossignol P, Zannad F
Background
Loop diuretics are the mainstay of congestion treatment in patients with heart failure (HF). We assessed the association between baseline loop diuretic use and outcome. We also compared the increment in risk related to diuretic dose with conventional prognostic enrichment criteria used in the EMPHASIS-HF trial, which included patients with systolic HF and mild symptoms, such as prior hospitalization and elevated natriuretic peptides.
Methods
Individual analyses were performed according to baseline loop diuretic usage (furosemide-equivalent dose > 40 mg, 1-40 mg, and no furosemide), and according to enrichment criteria adopted in the trial [i.e. recent hospitalization (< 30 days or 30 to 180 days prior to randomization) due to HF or other cardiovascular cause, or elevated natriuretic peptides]. The primary endpoint was a composite of cardiovascular death or HF hospitalization.
Results
Loop diuretic usage at baseline (HR for > 40 mg furosemide-equivalent dose = 3.16, 95% CI 2.43-4.11; HR for 1-40 mg = 2.06, 95% CI 1.60-2.65) was significantly associated with a higher risk for the primary endpoint in a stepwise manner when compared to no baseline loop diuretic usage. In contrast, the differences in outcome rates were more modest when using history of hospitalization and/or BNP: all HR ranged from 1 (reference, non-HF related CV hospitalization > 30 days) to 2.04 (HF hospitalization < 30 days). The effect of eplerenone on the primary endpoint was consistent across subgroups in both analyses (P for interaction ≥ 0.2 for all).
Conclusions
Loop diuretic usage (especially at doses > 40 mg) identified patients at higher risk than history of HF hospitalization and/or high BNP blood concentrations.



Clin Res Cardiol: 05 May 2021; epub ahead of print
Coiro S, Girerd N, McMurray JJV, Pitt B, ... Rossignol P, Zannad F
Clin Res Cardiol: 05 May 2021; epub ahead of print | PMID: 33956209
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Impact:
Abstract

Admission blood glucose level and outcome in patients requiring venoarterial extracorporeal membrane oxygenation.

Bemtgen X, Rilinger J, Jäckel M, Zotzmann V, ... Lother A, Staudacher DL
Background
Patients with cardiogenic shock or cardiac arrest undergoing venoarterial extracorporeal membrane oxygenation (V-A ECMO) frequently present with blood glucose levels out of normal range. The clinical relevance of such findings in the context of V-A ECMO is unknown. We therefore investigated the prognostic relevance of blood glucose at time of cannulation for V-A ECMO.
Methods
We conducted a single-center retrospective registry study. All patients receiving V-A ECMO from October 2010 to January 2020 were included if blood glucose level at time of cannulation were documented. Patients were divided in five groups according to the initial blood glucose level ranging from hypoglycemic (< 80 mg/dl), normoglycemic (80-140 mg/dl), to mild (141-240 mg/dl), moderate (241-400 mg/dl), and severe (> 400 mg/dl) hyperglycemia, respectively. Clinical presentation, arterial blood gas analysis, and survival were compared between the groups.
Results
392 patients met inclusion criteria. Median age was 62 years (51.5-70.0), SAPS II at admission was 54 (43.5-63.0), and 108/392 (27.6%) were female. 131/392 were discharged alive (hospital survival 33.4%). At time of cannulation, survivors had higher pH, hemoglobin, calcium, bicarbonate but lower potassium and lactate levels compared to non-survivors (all p < 0.01). Outcome of patients diagnosed with particularly high (> 400 mg/dl) and low (< 80 mg/dl) blood glucose at time of V-A ECMO cannulation, respectively, was worse compared to patients with normoglycemic, mildly or moderately elevated values (p = 0.02). Glucose was independently associated with poor outcome after adjustment for other predictors of survival and persisted in all investigated subgroups.
Conclusion
Arterial blood glucose at time of V-A ECMO cannulation predicts in-hospital survival of patients with cardiac shock or after ECPR. Whether dysglycemia represents a potential therapeutic target requires further evaluation in prospective studies.



Clin Res Cardiol: 03 May 2021; epub ahead of print
Bemtgen X, Rilinger J, Jäckel M, Zotzmann V, ... Lother A, Staudacher DL
Clin Res Cardiol: 03 May 2021; epub ahead of print | PMID: 33944987
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Impact:
Abstract

Impact of the introduction of percutaneous edge-to-edge mitral valve reconstruction on clinical practice in Germany compared to surgical valve repair.

Frankenstein L, Kaier K, Katus HA, Bode C, ... Fröhlich H, Stachon P
Background
The introduction of percutaneous mitral valve (MV) repair had an effect on clinical practice in comparison with surgical MV repair. Complete nationwide data are useful in examining how the introduction of a new technique influences clinical practice.
Methods
We analyzed procedural numbers, patient characteristics, and in-hospital outcomes for all percutaneous edge-to-edge and surgical MV reconstruction procedures performed in Germany between 2009 and 2015.
Results
12,664 percutaneous edge-to-edge and 22,825 surgical MV reconstructions were recorded. Numbers increased steadily, albeit more rapidly in the percutaneous edge-to-edge group (108-4079 vs. 2923-3603 with surgical MV reconstruction). Patients with percutaneous edge-to-edge MV reconstruction were older (75.6 ± 8.8 vs 61.6 ± 13.4 years, P < 0.001) and at higher operative risk (estimated logistic EuroSCORE 13.2% vs. 4.7%, P < 0.001) compared to those undergoing surgery. However, in-hospital mortality did not differ (2.9% vs. 2.8%; P = 0.395). This was also true for the subset of 2103 patients at intermediate operative risk as defined by a logistic EuroSCORE ≥ 4% and ≤ 9%. Of note, complication rates (except acute kidney injury) were more favorable in patients undergoing percutaneous edge-to-edge reconstruction.
Conclusions
Percutaneous edge-to-edge MV reconstruction has markedly changed clinical practice of MR therapy in Germany. Annual overall procedural numbers more than doubled, with a massive increase in percutaneous edge-to-edge procedures. Our data demonstrate its use mainly in high-risk patients and prove the favorable safety profile of this novel technique, with low in-hospital mortality and complication rates.



Clin Res Cardiol: 29 Apr 2021; 110:620-627
Frankenstein L, Kaier K, Katus HA, Bode C, ... Fröhlich H, Stachon P
Clin Res Cardiol: 29 Apr 2021; 110:620-627 | PMID: 32462266
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Impact:
Abstract

Myocardial salvage is increased after sympathetic renal denervation in a pig model of acute infarction.

Pastormerlo LE, Burchielli S, Ciardetti M, Aquaro GD, ... Passino C, Emdin M
Rationale
Despite advances in treatment of acute myocardial infarction (AMI), many patients suffer significant myocardial damage with cardiac dysfunction. Sympathetic renal denervation (RD) may reduce adrenergic activation following AMI.
Objective
To investigate the potential role of RD limiting myocardial damage and remodeling when performed immediately after AMI.
Methods and results
Sixteen farm pigs underwent 90 min left anterior descending artery balloon occlusion. Eight pigs underwent RD immediately after reperfusion. LV function, extent of myocardium at risk, and myocardial necrosis were quantified by cardiac magnetic resonance 5 and 30 days after AMI. 123I-MIBG scintigraphy was performed 31 days after AMI to image myocardial sympathetic innervation. Heart norepinephrine was quantified (from necrotic, border and remote zone). RD and control did not differ in myocardium at risk extent (59 ± 9 vs 55 ± 11% of LV mass) at 5 days. At 30 days CMR, RD pigs had smaller necrotic areas than control as assessed by gadolinium delay enhancement (18 ± 7 vs 30 ± 12% of LV mass, p = 0.021) resulting in improved myocardial salvage index (60 ± 11 vs 44 ± 27%, p < 0.001). RD pigs had higher cardiac output (3.7 ± 0.8 vs 2.66 ± 0.7 L/min, p < 0.001) and lower LV end diastolic volume (98 ± 16 vs 113 ± 31 ml, p = 0.041). 123I-MIBG defect extension was smaller in RD than control (60 ± 28 vs 78 ± 17%, p < 0.05) with significant reduction in the difference between innervation and perfusion defects (25 ± 12 vs 36 ± 30%, p = 0.013). NE content from necrotic area (238; IQR 464 vs 2546; IQR 1727 ng/g in RD and control, respectively, p < 0.001) and from border zone (295; IQR 264 vs 837; IQR 207 in RD and control, respectively, p = 0.031) was significantly lower in RD than control.
Conclusions
RD results in increased myocardial salvage and better cardiac function, when performed immediately after AMI. Reduction of sympathetic activation with preservation of cardiac sympathetic functionality warranted by RD may sustain these effects.



Clin Res Cardiol: 29 Apr 2021; 110:711-724
Pastormerlo LE, Burchielli S, Ciardetti M, Aquaro GD, ... Passino C, Emdin M
Clin Res Cardiol: 29 Apr 2021; 110:711-724 | PMID: 32514602
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Impact:
Abstract

Effect of renal denervation in attenuating the stress of morning surge in blood pressure: post-hoc analysis from the SPYRAL HTN-ON MED trial.

Kario K, Weber MA, Böhm M, Townsend RR, ... Fahy M, Kandzari DE
Background
Catheter-based renal denervation (RDN) reduces blood pressure (BP) throughout the 24-h period, as reported in several randomized sham-controlled trials. Reduction of BP in the early morning hours is especially important due to increased cardiovascular risks during that time.
Objective
In this report, we examine the impact of RDN on systolic BP (SBP) and diastolic BP (DBP) during the critical morning surge period in a post-hoc analysis of patients in the SPYRAL HTN-ON MED trial.
Methods and results
Ambulatory BP measurements were collected at baseline and 6 months for treatment and control patient groups over 24-h periods. Average morning BP surge is the difference between average morning BP and average nighttime BP, and the morning surge slope reflects the rate of change of BP from nighttime to morning. Mean morning DBP surge slopes were significantly lower for RDN vs. control groups at 6 months (1.1 vs. 3.6 mmHg/h; p = 0.029). In the RDN group, morning DBP surge slopes were significantly lower at 6 months compared to baseline (1.1 vs. 4.1 mmHg/h; p = 0.006). Similar patterns were observed for mean morning SBP surge slope but did not reach statistical significance.
Conclusions
This decrease in the morning DBP surge slope, an index of the sympathetically-mediated morning BP surge, thus indicates a drop in late morning BP relative to early morning/nocturnal BP in the RDN group. Thus, RDN appears effective in attenuating the slope of morning surge in DBP that might indicate possible benefits in a high-risk hypertensive population.
Clinical trial registration
https://www.clinicaltrials.gov (NCT02439775), registered May 12, 2015.



Clin Res Cardiol: 29 Apr 2021; 110:725-731
Kario K, Weber MA, Böhm M, Townsend RR, ... Fahy M, Kandzari DE
Clin Res Cardiol: 29 Apr 2021; 110:725-731 | PMID: 32740754
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Impact:
Abstract

Mid-term hemodynamic and functional results after transcatheter mitral valve leaflet repair with the new PASCAL device.

Barth S, Hautmann MB, Arvaniti E, Kikec J, ... Lüsebrink U, Hamm K
Aims
To examine the functional and hemodynamic mid-term outcome at 5 months of mitral regurgitation (MR) reduction using the PASCAL repair system.
Methods and results
Between July 2019 and February 2020 31 consecutive patients with MR 3 +/4 + (mean age 77.5 years, all in New York Heart Association (NYHA) class III-IV, STS score 9.1 ± 7.4) underwent MR reduction in our institute using the PASCAL device. 61.3% had a functional, 29.0% a degenerative, and 9.7% a mixed etiology. Successful implantation was achieved in 30/31 (96.8%) patients. 27/31 patients (87.1%) completed 5-month follow-up with clinical, echocardiographic, laboratory and hemodynamic assessment. At 5 months, 70.4% of the patients had MR grade ≤ 1 (p < 0.001). 85.2% were in NYHA class I or II (p < 0.001). Six-minute walk distance improved by 145 m (p = 0.010), Kansas City cardiomyopathy questionnaire and European quality of life 5 dimensions questionnaire (EQ5D) improved by 31 (p < 0.001) and 9 points (p = 0.001), respectively. Mean pulmonary capillary wedge pressure decreased significantly from 22.1 ± 9 mmHg to 17.3 ± 8 mmHg (p = 0.041) and right atrial pressure from 10.3 ± 6 mmHg to 8.0 ± 6 mmHg (p = 0.013) from baseline to 5 months. In addition, propensity score matching showed that PASCAL and MitraClip procedures resulted in equally hemodynamic and functional improvement.
Conclusion
MR reduction of severe MR with the PASCAL device is feasible and safe regardless of etiologies. Mid-term follow-up at 5 months showed a sustained MR reduction, improvement of exercise capacity, quality of life, proBNP levels and hemodynamics regarding pulmonary capillary wedge pressure and right atrial pressure.



Clin Res Cardiol: 29 Apr 2021; 110:628-639
Barth S, Hautmann MB, Arvaniti E, Kikec J, ... Lüsebrink U, Hamm K
Clin Res Cardiol: 29 Apr 2021; 110:628-639 | PMID: 32845361
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Impact:
Abstract

Thirty-day incidence of stroke after transfemoral transcatheter aortic valve implantation: meta-analysis and mixt-treatment comparison of self-expandable versus balloon-expandable valve prostheses.

Seppelt PC, Mas-Peiro S, De Rosa R, Dimitriasis Z, Zeiher AM, Vasa-Nicotera M
Aims
Stroke is a major complication after transcatheter aortic valve implantation (TAVI). Although multifactorial, it remains unknown whether the valve deployment system itself has an impact on the incidence of early stroke. We performed a meta- and network analysis to investigate the 30-day stroke incidence of self-expandable (SEV) and balloon-expandable (BEV) valves after transfemoral TAVI.
Methods and results
Overall, 2723 articles were searched directly comparing the performance of SEV and BEV after transfemoral TAVI, from which 9 were included (3086 patients). Random effects models were used for meta- and network meta-analysis based on a frequentist framework. Thirty-day incidence of stroke was 1.8% in SEV and 3.1% in BEV (risk ratio of 0.62, 95% confidence interval (CI) 0.49-0.80, p = 0.004). Treatment ranking based on network analysis (P-score) revealed CoreValve with the best performance for 30-day stroke incidence (75.2%), whereas SAPIEN had the worst (19.0%). However, network analysis showed no inferiority of SAPIEN compared with CoreValve (odds ratio 2.24, 95% CI 0.70-7.2).
Conclusion
Our analysis indicates higher 30-day stroke incidence after transfemoral TAVI with BEV compared to SEV. We could not find evidence for superiority of a specific valve system. More randomized controlled trials with head-to-head comparison of SEV and BEV are needed to address this open question.



Clin Res Cardiol: 29 Apr 2021; 110:640-648
Seppelt PC, Mas-Peiro S, De Rosa R, Dimitriasis Z, Zeiher AM, Vasa-Nicotera M
Clin Res Cardiol: 29 Apr 2021; 110:640-648 | PMID: 33249517
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Impact:
Abstract

Impact of frailty on periprocedural health care utilization in patients undergoing transcatheter edge-to-edge mitral valve repair.

Iliadis C, Schwabe L, Müller D, Stock S, Baldus S, Pfister R
Background
Frailty is a common characteristic of patients undergoing transcatheter mitral valve repair (TMVR). It is unclear whether the physical vulnerability of frail patients translates into increased procedural health care utilization.
Methods and results
Frailty was assessed using the Fried criteria in 229 patients undergoing TMVR using the MitraClip system at our institution and associations with total costs and costs by cost centers within the hospital incurred during periprocedural hospitalization were examined. Frail patients (n = 107, 47%) compared to non-frail patients showed significantly higher total costs [median/interquartile range, excluding implant costs: 7,337 € (5,911-9,814) vs 6,238 € (5,584-7,499), p = 0.001], with a difference in means of 2,317 €. Frailty was the only clinical baseline characteristic with significant association with total costs. Higher total costs in frail patients were attributable primarily to longer stay on intermediate/intensive care unit (3.8 ± 5.7 days in frail vs 2.1 ± 1.7 days in non-frail, p = 0.003), but also to costs of clinical chemistry and physiotherapy. The prolonged stay on intermediate/intensive care unit in frail patients was attributable to postprocedural complications such as bleeding, kidney injury, infections and cardiovascular instability.
Conclusion
Frailty is associated with a mean 32% increase of hospital costs in patients undergoing TMVR, which is primarily the result of a prolonged recovery and increased vulnerability to complications. These findings are valuable for a hospital\'s total cost calculation and resource allocation planning. Since frailty is regarded a potentially reversible health state, preventive interventions may help reduce costs in frail patients.



Clin Res Cardiol: 29 Apr 2021; 110:658-666
Iliadis C, Schwabe L, Müller D, Stock S, Baldus S, Pfister R
Clin Res Cardiol: 29 Apr 2021; 110:658-666 | PMID: 33336304
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Impact:
Abstract

Predictors of high residual gradient after transcatheter aortic valve replacement in bicuspid aortic valve stenosis.

Bugani G, Pagnesi M, Tchetchè D, Kim WK, ... Colombo A, Mangieri A
Objectives
To define the incidence of high residual gradient (HRG) after transcatheter aortic valve replacement (TAVR) in BAVs and their impact on short term outcome and 1-year mortality.
Background
Transcatheter heart valves (THVs) offer good performance in tricuspid aortic valves with low rate of HRG. However, data regarding their performance in bicuspid aortic valves (BAV) are still lacking.
Methods
The BEAT (Balloon vs Self-Expandable valve for the treatment of bicuspid Aortic valve sTenosis) registry included 353 consecutive patients who underwent TAVR (Evolut R/PRO or Sapien 3 valves) in BAV between June 2013 and October 2018. The primary endpoint was device unsuccess with post-procedural HRG (mean gradient ≥ 20 mmHg). The secondary endpoint was to identify the predictors of HRG following the procedure.
Results
Twenty patients (5.6%) showed HRG after TAVR. Patients with HRG presented higher body mass index (BMI) (30.7 ± 9.3 vs. 25.9 ± 4.8; p < 0.0001) and higher baseline aortic mean gradients (57.6 ± 13.4 mmHg vs. 47.7 ± 16.6, p = 0.013) and more often presented with BAV of Sievers type 0 than patients without HRG. At multivariate analysis, BMI [odds ratio (OR) 1.12; 95% confidence interval (CI) 1.05-1.20, p = 0.001] and BAV type 0 (OR 11.31, 95% CI 3.45-37.06, p < 0.0001) were confirmed as independent predictors of high gradient.
Conclusion
HRG following TAVR in BAVs is not negligible and is higher among patients with high BMI and with BAV 0 anatomy.



Clin Res Cardiol: 29 Apr 2021; 110:667-675
Bugani G, Pagnesi M, Tchetchè D, Kim WK, ... Colombo A, Mangieri A
Clin Res Cardiol: 29 Apr 2021; 110:667-675 | PMID: 33389062
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Impact:
Abstract

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

Geyer M, Keller K, Bachmann K, Born S, ... Münzel T, von Bardeleben RS
Background
Concomitant tricuspid regurgitation (TR) is a common finding in mitral regurgitation (MR). Transcatheter repair (TMVR) is a favorable treatment option in patients at elevated surgical risk. To date, evidence on long-term prognosis and the prognostic impact of TR after TMVR is limited.
Methods
Long-term survival data of patients undergoing isolated edge-to-edge repair from June 2010 to March 2018 (combinations with other forms of TMVR or tricuspid valve therapy excluded) were analyzed in a retrospective monocentric study. TR severity was categorized and the impact of TR on survival was analysed.
Results
Overall, 606 patients [46.5% female, 56.4% functional MR (FMR)] were enrolled in this study. TR at baseline was categorized severe/medium/mild/no or trace in 23.2/34.3/36.3/6.3% of the cases. At 30-day follow-up, improvement of at least one TR-grade was documented in 34.9%. Severe TR at baseline was identified as predictor of 1-year survival [65.2% vs. 77.0%, p = 0.030; HR for death 1.68 (95% CI 1.12-2.54), p = 0.013] and in FMR-patients also regarding long-term prognosis [adjusted HR for long-term mortality 1.57 (95% CI 1.00-2.45), p = 0.049]. Missing post-interventional reduction of TR severity was predictive for poor prognosis, especially in the FMR-subgroup [1-year survival: 92.9% vs. 78.3%, p = 0.025; HR for death at 1-year follow-up 3.31 (95% CI 1.15-9.58), p = 0.027]. While BNP levels decreased in both subgroups, TR reduction was associated with improved symptomatic benefit (NYHA-class-reduction 78.6 vs. 65.9%, p = 0.021).
Conclusion
In this large study, both, severe TR at baseline as well as missing secondary reduction were predictive for impaired long-term prognosis, especially in patients with FMR etiology. TR reduction was associated with increased symptomatic benefit.



Clin Res Cardiol: 29 Apr 2021; 110:676-688
Geyer M, Keller K, Bachmann K, Born S, ... Münzel T, von Bardeleben RS
Clin Res Cardiol: 29 Apr 2021; 110:676-688 | PMID: 33433670
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Impact:
Abstract

Impact of sinus rhythm versus atrial fibrillation on left ventricular remodeling after transcatheter aortic valve replacement.

Ledwoch J, Fröhlich C, Olbrich I, Poch F, ... Kupatt C, Hoppmann P
Aims
Atrial fibrillation (AF) is associated with increased mortality after transcatheter aortic valve replacement (TAVR). Cerebrovascular complications and bleeding events associated with anticoagulation therapy are discussed to be possible causes for this increased mortality. The present study sought to assess whether AF is associated with impaired left ventricular (LV) reverse remodeling representing another possible mechanism for poor outcome.
Methods
All patients who underwent TAVR in our institution and had 1-year echocardiography follow-up were included. LV mass index (LVMI) at baseline and follow-up as well as LVMI change at 1 year were assessed with respect to the presence of AF (either at baseline or during hospitalization after TAVR) and sinus rhythm (SR).
Results
A total of 213 patients (n = 95 in AF; n = 118 in SR) were enrolled in the present study. Patients with AF had higher LVMI at 1 year compared to those with SR (173 ± 61 g/m2 vs. 154 ± 55 g/m2; p = 0.02) and they showed lower relative LVMI change at 1 year (- 2 ± 28% vs. - 9 ± 29%; p = 0.04). In linear regression analysis, AF was independently associated with relative LVMI change (regression coefficient ß 0.076 [95% CI 0.001-0.150]; p = 0.04). With respect to clinical outcome depending on AF and LVMI regression, the Kaplan-Meier estimated event-free of death or cardiac rehospitalization at 3 years was lowest among patients with AF and no LVMI regression.
Conclusions
The present study identified a significant association of AF with changes in LVMI after TAVR, which was also shown to be associated with clinical outcome.



Clin Res Cardiol: 29 Apr 2021; 110:689-698
Ledwoch J, Fröhlich C, Olbrich I, Poch F, ... Kupatt C, Hoppmann P
Clin Res Cardiol: 29 Apr 2021; 110:689-698 | PMID: 33566184
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Impact:
Abstract

Combined renal and common hepatic artery denervation as a novel approach to reduce cardiometabolic risk: technical approach, feasibility and safety in a pre-clinical model.

Kiuchi MG, Ganesan K, Keating J, Carnagarin R, ... Adams L, Schlaich MP
Background
Cardiovascular and metabolic regulation is governed by neurohumoral signalling in relevant organs such as kidney, liver, pancreas, duodenum, adipose tissue, and skeletal muscle. Combined targeting of relevant neural outflows may provide a unique therapeutic opportunity for cardiometabolic disease.
Objectives
We aimed to investigate the feasibility, safety, and performance of a novel device-based approach for multi-organ denervation in a swine model over 30 and 90 days of follow-up.
Methods
Five Yorkshire cross pigs underwent combined percutaneous denervation in the renal arteries and the common hepatic artery (CHA) with the iRF Denervation System. Control animals (n = 3) were also studied. Specific energy doses were administered in the renal arteries and CHA. Blood was collected at 30 and 90 days. All animals had a pre-terminal procedure angiography. Tissue samples were collected for norepinephrine (NEPI) bioanalysis. Histopathological evaluation of collateral structures and tissues near the treatment sites was performed to assess treatment safety.
Results
All animals entered and exited the study in good health. No stenosis or vessel abnormalities were present. No significant changes in serum chemistry occurred. NEPI concentrations were significantly reduced in the liver (- 88%, p = 0.005), kidneys (- 78%, p < 0.001), pancreas (- 78%, p = 0.018) and duodenum (- 95%, p = 0.028) following multi-organ denervation treatment compared to control animals. Histologic findings were consistent with favourable tissue responses at 90 days follow-up.
Conclusions
Significant and sustained denervation of the treated organs was achieved at 90 days without major safety events. Our findings demonstrate the feasibility of multi-organ denervation using a novel iRF Denervation System in a single procedure.



Clin Res Cardiol: 29 Apr 2021; 110:740-753
Kiuchi MG, Ganesan K, Keating J, Carnagarin R, ... Adams L, Schlaich MP
Clin Res Cardiol: 29 Apr 2021; 110:740-753 | PMID: 33635438
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Impact:
Abstract

Outcome of aortic stenosis according to invasive cardiac damage staging after transcatheter aortic valve replacement.

Schewel J, Kuck KH, Frerker C, Schmidt T, Schewel D
Background
In recent studies, a 5-stage cardiac damage classification in severe aortic stenosis (AS) based on echocardiographic parameters has shown to provide predictive value regarding clinical outcome. The objective of this study was to investigate the prognostic impact of a cardiac damage classification based on invasive hemodynamics in patients with AS undergoing transcatheter aortic valve replacement (TAVR).
Methods
A total of 1400 patients with symptomatic AS and full invasive hemodynamic assessment before TAVR were included. Patients were categorized according to their cardiac damage stage into five groups that are defined as: stage 0, no cardiac damage; stage 1, left ventricular damage; stage 2, left atrial and/or mitral valve damage; stage 3, pulmonary vasculature and/or tricuspid valve damage; stage 4, right ventricular damage.
Results
9.9% patients were classified as stage 0, 23.6% as stage 1, the majority of patients as stage 2 (33.5%), 23.1% as stage 3 and 10% as stage 4. One- and 4-year mortality were 10.1%/29.5% in stage 0, 16.1%/60.6% in stage 1, 17.3%/39.4% in stage 2, 22%/54.6% in stage 3, 27.1%/62.2% in stage 4 (p = 0.001/p < 0.001). The extent of cardiac damage was independently associated with increased mortality after TAVR (HR 1.16 per each increment in stage, 95% confidence interval 1.03-1.18; p = 0.018).
Conclusions
Cardiac damage staging in severe AS patients based on invasive hemodynamics appears to show strong association between the extent of cardiac damage and post-TAVR mortality. This staging classification provides predictive value and may improve risk stratification, therapy management and decision-making in patients with AS. Invasive Staging Classification of Cardiac Damage in Severe Symptomatic Aortic Stenosis has an Impact on Outcome after TAVR. (Top) Invasive staging criteria for cardiac damage in five stages using left ventricular end-diastolic pressure (LVEDP) for stage 1 (red), post-capillary wedge pressure (PCWP) for stage 2 (green), systolic pulmonary artery pressure (SPAP) for stage 3 (purple) and right atrial pressure (RAP) for stage 4 (yellow). The cake chart shows the distribution of the different stage in the whole cohort. (Bottom) Survival Analyses According to Stage of Cardiac Damage after Transcatheter Aortic Valve Replacement using Invasive Criteria. Kaplan-Meier plots comparing overall (left) and cardiovascular (right) 4-year survival showing with the more advancing stage a higher mortality rate.



Clin Res Cardiol: 29 Apr 2021; 110:699-710
Schewel J, Kuck KH, Frerker C, Schmidt T, Schewel D
Clin Res Cardiol: 29 Apr 2021; 110:699-710 | PMID: 33744987
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Impact:
Abstract

Imaging strategies for safety surveillance after renal artery denervation.

Cohen DL, Weinberg I, Uretsky S, Popma JJ, ... Cohen SA, Townsend RR
Renal denervation has emerged as a safe and effective therapy to lower blood pressure in hypertensive patients. In addition to the main renal arteries, branch vessels are also denervated in more contemporary studies. Accurate and reliable imaging in renal denervation patients is critical for long-term safety surveillance due to the small risk of renal artery stenosis that may occur after the procedure. This review summarizes three common non-invasive imaging modalities: Doppler ultrasound (DUS), computed tomography angiography (CTA), and magnetic resonance angiography (MRA). DUS is the most widely used owing to cost considerations, ease of use, and the fact that it is less invasive, avoids ionizing radiation exposure, and requires no contrast media use. Renal angiography is used to determine if renal artery stenosis is present when non-invasive imaging suggests renal artery stenosis. We compiled data from prior renal denervation studies as well as the more recent SPYRAL-HTN OFF MED Study and show that DUS demonstrates both high sensitivity and specificity for detecting renal stenosis de novo and in longitudinal assessment of renal artery patency after interventions. In the context of clinical trials DUS has been shown, together with the use of the baseline angiogram, to be effective in identifying stenosis in branch and accessory arteries and merits consideration as the main screening imaging modality to detect clinically significant renal artery stenosis after renal denervation and this is consistent with guidelines from the recent European Consensus Statement on Renal Denervation.



Clin Res Cardiol: 29 Apr 2021; 110:609-619
Cohen DL, Weinberg I, Uretsky S, Popma JJ, ... Cohen SA, Townsend RR
Clin Res Cardiol: 29 Apr 2021; 110:609-619 | PMID: 33646357
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Abstract

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

Karam N, Orban M, Kalbacher D, Butter C, ... Hausleiter J, EuroSMR investigators
Objectives
To assess the value of effective regurgitant orifice (ERO) in predicting outcome after edge-to-edge transcatheter mitral valve repair (TMVR) for secondary mitral regurgitation (SMR) and identify the optimal cut-off for patients\' selection.
Methods
Using the EuroSMR (European Registry of Transcatheter Repair for Secondary Mitral Regurgitation) registry, that included patients undergoing edge-to-edge TMVR for SMR between November 2008 and January 2019 in 8 experienced European centres, we assessed the optimal ERO threshold associated with mortality in SMR patients undergoing TMVR, and compared characteristics and outcomes of patients according to baseline ERO.
Results
Among 1062 patients with severe SMR and ERO quantification by proximal isovelocity surface area method in the registry, ERO was < 0.3 cm2 in 575 patients (54.1%), who were more symptomatic at baseline (NYHA class ≥ III: 91.4% vs. 86.9%, for ERO < vs. ≥ 0.3 cm2; P = 0.004). There was no difference in all-cause mortality at 2-year follow-up according to baseline ERO (28.3% vs. 30.0% for ERO < vs. ≥ 0.3 cm2, P = 0.585). Both patient groups demonstrated significant improvement of at least one NYHA class (61.7% and 73.8%, P = 0.002), resulting in a prevalence of NYHA class ≤ II at 1-year follow-up of 60.0% and 67.4% for ERO < vs. ≥ 0.3 cm2, respectively (P = 0.05).
Conclusion
All-cause mortality at 2 years after TMVR does not differ if baseline ERO is < or ≥ 0.3 cm2, and both groups exhibit relevant clinical improvements. Accordingly, TMVR should not be withheld from patients with ERO < 0.3 cm2 who remain symptomatic despite optimal medical treatment, if TMVR appropriateness was determined by experienced teams in dedicated valve centres.



Clin Res Cardiol: 29 Apr 2021; 110:732-739
Karam N, Orban M, Kalbacher D, Butter C, ... Hausleiter J, EuroSMR investigators
Clin Res Cardiol: 29 Apr 2021; 110:732-739 | PMID: 33661372
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Abstract

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

Chandrasekhar J, Sartori S, Mehran R, Aquino M, ... Anthopoulos P, Dangas GD
Background
Acute kidney injury (AKI) is not uncommon in patients undergoing transcatheter aortic valve replacement (TAVR).
Objective
We examined the incidence, predictors, and outcomes of AKI from the BRAVO 3 randomized trial.
Methods
The BRAVO-3 trial included 802 patients undergoing transfemoral TAVR randomized to bivalirudin vs. unfractionated heparin (UFH). The primary endpoint of the trial was Bleeding Academic Research Consortium (BARC) type ≥ 3b bleeding at 48 h. Total follow-up was to 30 days. AKI was adjudicated using the modified RIFLE (Valve Academic Research Consortium, VARC 1) criteria through 30-day follow-up, and in a sensitivity analysis AKI was assessed at 7 days (modified VARC-2 criteria). We examined the incidence, predictors, and 30-day outcomes associated with diagnosis of AKI. We also examined the effect of procedural anticoagulant (bivalirudin or unfractionated heparin, UFH) on AKI within 48 h after TAVR.
Results
The trial population had a mean age of 82.3 ± 6.5 years including 48.8% women with mean EuroScore I 17.05 ± 10.3%. AKI occurred in 17.0% during 30-day follow-up and was associated with greater adjusted risk of 30-day death (13.0% vs. 3.5%, OR 5.84, 95% CI 2.62-12.99) and a trend for more BARC ≥ 3b bleeding (15.1% vs. 8.6%, OR 1.80, 95% CI 0.99-3.25). Predictors of 30-day AKI were baseline hemoglobin, body weight, and pre-existing coronary disease. AKI occurred in 10.7% at 7 days and was associated with significantly greater risk of 30-day death (OR 6.99, 95% CI 2.85-17.15). Independent predictors of AKI within 7 days included pre-existing coronary or cerebrovascular disease, chronic kidney disease (CKD), and transfusion which increased risk, whereas post-dilation was protective. The incidence of 48-h AKI was higher with bivalirudin compared to UFH in the intention to treat cohort (10.9% vs. 6.5%, p = 0.03), but not in the per-protocol assessment (10.7% vs. 7.1%, p = 0.08).
Conclusion
In the BRAVO 3 trial, AKI occurred in 17% at 30 days and in 10.7% at 7 days. AKI was associated with a significantly greater adjusted risk for 30-day death. Multivariate predictors of AKI at 30 days included baseline hemoglobin, body weight, and prior coronary artery disease, and predictors at 7 days included pre-existing vascular disease, CKD, transfusion, and valve post-dilation. Bivalirudin was associated with greater AKI within 48 h in the intention to treat but not in the per-protocol analysis.



Clin Res Cardiol: 29 Apr 2021; 110:649-657
Chandrasekhar J, Sartori S, Mehran R, Aquino M, ... Anthopoulos P, Dangas GD
Clin Res Cardiol: 29 Apr 2021; 110:649-657 | PMID: 33839885
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Abstract

Influence of sex, age and race on coronary and heart failure events in patients with diabetes and post-acute coronary syndrome.

Rossello X, Ferreira JP, Caimari F, Lamiral Z, ... White WB, Zannad F
Background
Women, older patients and non-White ethnic groups experience a substantial proportion of acute coronary syndromes (ACS), although they have been historically underrepresented in ACS randomized clinical trials (RCTs). To assess the influence of sex, age and race on major adverse cardiovascular events (MACE) and on heart failure events, we studied patients with type 2 diabetes in a large post-ACS trial (EXAMINE).
Methods
Differences in baseline characteristics and the respective composite endpoint of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (MACE) and cardiovascular death or heart failure hospitalization (HF events) were evaluated by subgroups in a cohort of post-ACS patients with diabetes, using unadjusted and adjusted Cox regression modelling.
Results
The EXAMINE trial enrolled 5380 patients with 35% aged > 65, 32% female and 27% non-White. The risk of MACE was higher in non-White compared to White patients after adjustment for potential confounding (HR = 1.35; 95% CI 1.04-1.75), but there were no significant differences by sex and age (HR = 1.03; 95% CI 0.87-1.22 for women; HR = 1.14; 95% CI 0.96-1.35 for patients ≥ 65 years). The risk of HF events was higher in non-White patients (HR = 1.56; 95% CI 1.13-2.14), and in patients aged > 65 (HR = 1.33; 95% CI 1.07-1.66) and nominally so in women (HR = 1.23; 95% CI 0.99-1.52). The additive risk of each demographic factor (women, older age and non-White race) was greater for HF events in comparison with MACE. Moreover, non-White elderly patients consistently had poorer prognosis regardless of sex.
Conclusions
Older adults, women and non-White patients with diabetes who are post-ACS are often underrepresented in RCTs. The risk for HF events was higher in older and non-White patients, with a trend towards significance in women, whereas only non-White patients (and not women and older patients) were at higher risk for MACE. Future trials should enrich enrollment of these persons at risk.



Clin Res Cardiol: 29 Apr 2021; epub ahead of print
Rossello X, Ferreira JP, Caimari F, Lamiral Z, ... White WB, Zannad F
Clin Res Cardiol: 29 Apr 2021; epub ahead of print | PMID: 33929598
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Abstract

Echocardiographic diagnosis of atrial cardiomyopathy allows outcome prediction following pulmonary vein isolation.

Eichenlaub M, Mueller-Edenborn B, Minners J, Allgeier M, ... Arentz T, Jadidi A
Background
Relevant atrial cardiomyopathy (ACM), defined as a left atrial (LA) low-voltage area ≥ 2 cm2 at 0.5 mV threshold on endocardial contact mapping, is associated with new-onset atrial fibrillation (AF), higher arrhythmia recurrence rates after pulmonary vein isolation (PVI), and an increased risk of stroke. The current study aimed to assess two non-invasive echocardiographic parameters, LA emptying fraction (EF) and LA longitudinal strain (LAS, during reservoir (LASr), conduit (LAScd) and contraction phase (LASct)) for the diagnosis of ACM and prediction of arrhythmia outcome after PVI.
Methods
We prospectively enrolled 60 consecutive, ablation-naive patients (age 66 ± 9 years, 80% males) with persistent AF. In 30 patients (derivation cohort), LA-EF and LAS cut-off values for the presence of relevant ACM (high-density endocardial contact mapping in sinus rhythm prior to PVI at 3000 ± 1249 sites) were established in sinus rhythm and tested in a validation cohort (n = 30). Arrhythmia recurrence within 12 months was documented using 72-h Holter electrocardiograms.
Results
An LA-EF of < 34% predicted ACM with an area under the curve (AUC) of 0.846 (sensitivity 69.2%, specificity 76.5%) similar to a LASr < 23.5% (AUC 0.878, sensitivity 92.3%, specificity 82.4%). In the validation cohort, these cut-offs established the correct diagnosis of ACM in 76% of patients (positive predictive values 87%/93% and negative predictive values 73%/75%, respectively). Arrhythmia recurrence in the entire cohort was significantly more frequent in patients with LA-EF < 34% and LASr < 23.5% (56% vs. 29% and 55% vs. 26%, both p < 0.05).
Conclusion
The echocardiographic parameters LA-EF and LAS allow accurate, non-invasive diagnosis of ACM and prediction of arrhythmia recurrence after PVI.



Clin Res Cardiol: 28 Apr 2021; epub ahead of print
Eichenlaub M, Mueller-Edenborn B, Minners J, Allgeier M, ... Arentz T, Jadidi A
Clin Res Cardiol: 28 Apr 2021; epub ahead of print | PMID: 33914144
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This program is still in alpha version.