Publications by authors named "Renate B Schnabel"

204 Publications

Treatment-Relevant Findings in Transesophageal Echocardiography After Stroke: A Prospective Multicenter Cohort Study.

Stroke 2021 Sep 9:STROKEAHA121034868. Epub 2021 Sep 9.

Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf, Germany (G.T., M.U., M.J., J.S., E.B., B.C., C.G.).

Background And Purpose: Cardiac ultrasound to identify sources of cardioembolism is part of the diagnostic workup of acute ischemic stroke. Recommendations on whether transesophageal echocardiography (TEE) should be performed in addition to transthoracic echocardiography (TTE) are controversial. We aimed to determine the incremental diagnostic yield of TEE in addition to TTE in patients with acute ischemic stroke with undetermined cause.

Methods: In a prospective, observational, pragmatic multicenter cohort study, patients with acute ischemic stroke or transient ischemic attack with undetermined cause before cardiac ultrasound were studied by TTE and TEE. The primary outcome was the rate of treatment-relevant findings in TTE and TEE as defined by a panel of experts based on current evidence. Further outcomes included the rate of changes in the assessment of stroke cause after TEE.

Results: Between July 1, 2017, and June 30, 2019, we enrolled 494 patients, of whom 492 (99.6%) received TTE and 454 (91.9%) received TEE. Mean age was 64.7 years, and 204 (41.3%) were women. TEE showed a higher rate of treatment-relevant findings than TTE (86 [18.9%] versus 64 [14.1%], <0.001). TEE in addition to TTE resulted in 29 (6.4%) additional patients with treatment-relevant findings. Among 191 patients ≤60 years additional treatment-relevant findings by TEE were observed in 27 (14.1%) patients. Classification of stroke cause changed after TEE in 52 of 453 patients (11.5%), resulting in a significant difference in the distribution of stroke cause before and after TEE (<0.001).

Conclusions: In patients with undetermined cause of stroke, TEE yielded a higher number of treatment-relevant findings than TTE. TEE appears especially useful in younger patients with stroke, with treatment-relevant findings in one out of seven patients ≤60 years.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03411642.
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http://dx.doi.org/10.1161/STROKEAHA.121.034868DOI Listing
September 2021

Gender differences in characteristics and outcomes in heart failure patients referred for end-stage treatment.

ESC Heart Fail 2021 Sep 6. Epub 2021 Sep 6.

Department of Cardiology, University Heart & Vascular Centre Hamburg, Martinistrasse 52, Hamburg, 20246, Germany.

Aims: Despite signals from clinical trials and mechanistic studies implying different resilience to heart failure (HF) depending on gender, the impact of gender on presentation and outcomes in patients with HF remains unclear. This study assessed the impact of gender on clinical presentation and outcomes in patients with HF referred to a specialised tertiary HF service.

Methods And Results: Consecutive patients with HF referred to a specialised tertiary HF service offering advanced therapy options including left ventricular assist devices (LVAD) and heart transplantation were prospectively enrolled from August 2015 until March 2018. We assessed clinical characteristics at baseline and performed survival analyses and age-adjusted Cox regression analyses in men vs. women for all-cause death and a combined disease-related endpoint comprising death, heart transplantation, and LVAD implantation. Analyses were performed for the overall study population and for patients with HF with reduced ejection fraction (HFrEF). Of 356 patients included, 283 (79.5%) were male. The median age was 58 years (interquartile range 50-67). Two hundred and fifty-one (74.5%) patients had HFrEF. HF aetiology, ejection fraction, functional status measures, and most of the cardiac and non-cardiac comorbidities did not differ between men and women. In a median follow-up of 3.2 years, 50 patients died (45 men, 5 women), 15 patients underwent LVAD implantation, and 8 patients heart transplantation. While all-cause death was not significantly different between both genders in the overall population [16.9 vs. 6.0%, P = 0.065, hazard ratio (HR) 2.29 (95% confidence interval 0.91-5.78), P = 0.078], in the HFrEF subgroup, a significant difference between men and women was observed [20.7% vs. 3.9%, P = 0.017, HR 3.67 (95% confidence interval 1.13-11.91), P = 0.031]. The combined endpoint was more often reached in men than in women in both the overall population [21.6% vs. 9.0%, P = 0.053, HR 2.51 (1.08-5.82), P = 0.032] and the HFrEF subgroup [27.1% vs. 7.7%, P = 0.015, HR 3.58 (1.29-9.94), P = 0.014].

Conclusions: Patients referred to a specialised tertiary HF service showed a similar clinical profile without relevant gender differences. In the mid-term follow-up, more male than female patients died or underwent heart transplantation and LVAD implantation. These findings call for independent validation and for further research into gender-specific drivers of HF progression.
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http://dx.doi.org/10.1002/ehf2.13567DOI Listing
September 2021

Applying the ESC 2016, H FPEF, and HFA-PEFF diagnostic algorithms for heart failure with preserved ejection fraction to the general population.

ESC Heart Fail 2021 Aug 29. Epub 2021 Aug 29.

Department of Cardiology, University Heart and Vascular Center Hamburg, Hamburg, Germany.

Aims: Heart failure with preserved ejection fraction (HFpEF) is common in patients presenting with dyspnoea. Recently, clinical tools were developed to facilitate the diagnosis of HFpEF. Here, we apply the European Society of Cardiology (ESC) 2016 heart failure guidelines and the H FPEF and HFA-PEFF scores to a middle-aged sample of the general population and compared the different groups with each other.

Methods And Results: This study included the first 10 000 participants of the population-based Hamburg City Health Study. A total of 5613 subjects, aged 62 ± 8.7 years (51.1% women), qualified for the analysis. Unexplained dyspnoea was present in 407 (7.3%) subjects. In those, the estimated prevalence of HFpEF was 20.4% (ESC 2016), 12.3% (H FPEF), and 7.6% (HFA-PEFF). The majority of subjects was classified as HFpEF not excludable according to the HFA-PEFF (57.7%) and H FPEF (59.2%) scores. For all algorithms, subjects diagnosed with HFpEF showed elevated age and body mass index as well as a higher prevalence of atrial fibrillation, diabetes, and arterial hypertension compared with those without HFpEF or HFpEF not excludable. The distribution of those co-morbidities and risk factors varied between the differently diagnosed HFpEF groups with the highest burden in the HFpEF group defined by the H FPEF score. The overlap of subjects diagnosed with HFpEF according to the different algorithms was very limited.

Conclusions: Unexplained dyspnoea is common in the middle-aged general population. The ESC 2016 algorithm and the H FPEF and HFA-PEFF scores detect different, discordant subpopulations of probands with breathlessness. Further classification of the HFpEF syndrome is desirable.
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http://dx.doi.org/10.1002/ehf2.13532DOI Listing
August 2021

Systematic, early rhythm control strategy for atrial fibrillation in patients with or without symptoms: the EAST-AFNET 4 trial.

Eur Heart J 2021 Aug 27. Epub 2021 Aug 27.

DZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Luebeck, Berlin, Germany.

Aims: Clinical practice guidelines restrict rhythm control therapy to patients with symptomatic atrial fibrillation (AF). The EAST-AFNET 4 trial demonstrated that early, systematic rhythm control improves clinical outcomes compared to symptom-directed rhythm control.

Methods And Results: This prespecified EAST-AFNET 4 analysis compared the effect of early rhythm control therapy in asymptomatic patients (EHRA score I) to symptomatic patients. Primary outcome was a composite of death from cardiovascular causes, stroke, or hospitalization with worsening of heart failure or acute coronary syndrome, analyzed in a time-to-event analysis. At baseline, 801/2633 (30.4%) patients were asymptomatic [mean age 71.3 years, 37.5% women, mean CHA2DS2-VASc score 3.4, 169/801 (21.1%) heart failure]. Asymptomatic patients randomized to early rhythm control (395/801) received similar rhythm control therapies compared to symptomatic patients [e.g. AF ablation at 24 months: 75/395 (19.0%) in asymptomatic; 176/910 (19.3%) symptomatic patients, P = 0.672]. Anticoagulation and treatment of concomitant cardiovascular conditions was not different between symptomatic and asymptomatic patients. The primary outcome occurred in 79/395 asymptomatic patients randomized to early rhythm control and in 97/406 patients randomized to usual care (hazard ratio 0.76, 95% confidence interval [0.6; 1.03]), almost identical to symptomatic patients. At 24 months follow-up, change in symptom status was not different between randomized groups (P = 0.19).

Conclusion: The clinical benefit of early, systematic rhythm control was not different between asymptomatic and symptomatic patients in EAST-AFNET 4. These results call for a shared decision discussing the benefits of rhythm control therapy in all patients with recently diagnosed AF and concomitant cardiovascular conditions (EAST-AFNET 4; ISRCTN04708680; NCT01288352; EudraCT2010-021258-20).
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http://dx.doi.org/10.1093/eurheartj/ehab593DOI Listing
August 2021

Refined atrial fibrillation screening and cost-effectiveness in the German population.

Heart 2021 Aug 10. Epub 2021 Aug 10.

University of Sydney, Charles Perkins Centre, Heart Research Institute, Sydney, New South Wales, Australia.

Objective: Little is known on optimal screening population for detecting new atrial fibrillation (AF) in the community. We describe characteristics and estimate cost-effectiveness for a single timepoint electrocardiographic screening.

Methods: We performed a 12-lead ECG in the German population-based Gutenberg Health Study between 2007 and 2012 (n=15 010), mean age 55±11 years, 51% men and collected more than 120 clinical and biomarker variables, including N-terminal pro B-type natriuretic peptide (Nt-proBNP), risk factors, disease symptoms and echocardiographic variables.

Results: Of 15 010 individuals, 466 (3.1%) had AF. New AF was found in 32 individuals, 0.2% of the total sample, 0.5% of individuals aged 65-74 years and predominantly men (86%). The classical risk factor burden was high in individuals with new AF. The median estimated stroke risk was 2.2%/year, while risk of developing heart failure was 21% over 10 years. In the 65-74 year age group, the cost per quality-adjusted life-year gained resulting from a single timepoint screening was €30 361. In simulations, the costs were highly sensitive to AF detection rates, proportion of treatment and type of oral anticoagulant. Prescreening by Nt-proBNP measurements was not cost-effective in the current setting.

Conclusions: In our middle-aged population cohort, we identified 0.2% new AF by single timepoint screening. There was a significant estimated risk of stroke and heart failure in these individuals. Cost-effectiveness for screening may be reached in individuals aged 65 years and older. The simple age cut-off is not improved by using Nt-proBNP as a biomarker to guide a screening programme.
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http://dx.doi.org/10.1136/heartjnl-2020-318882DOI Listing
August 2021

Genetics, atrial cardiomyopathy, and stroke: enough components for a sufficient cause?

Eur Heart J 2021 Aug 6. Epub 2021 Aug 6.

University Heart and Vascular Center Hamburg, Clinic for Cardiology, Hamburg, Germany.

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http://dx.doi.org/10.1093/eurheartj/ehab523DOI Listing
August 2021

Age-specific atrial fibrillation incidence, attributable risk factors and risk of stroke and mortality: results from the MORGAM Consortium.

Open Heart 2021 Jul;8(2)

Department of Cardiology, University Heart and Vascular Center Hamburg, Hamburg, Germany.

Background: The main aim was to examine age-specific risk factor associations with incident atrial fibrillation (AF) and their attributable fraction in a large European cohort. Additionally, we aimed to examine risk of stroke and mortality in relation to new-onset AF across age.

Methods: We used individual-level data (n=66 951, 49.1% men, age range 40-98 years at baseline) from five European cohorts of the MOnica Risk, Genetics, Archiving and Monograph Consortium. The participants were followed for incident AF for up to 10 years and the association with modifiable risk factors from the baseline examinations (body mass index (BMI), hypertension, diabetes, daily smoking, alcohol consumption and history of stroke and myocardial infarction (MI)) was examined. Additionally, the participants were followed up for incident stroke and all-cause mortality after new-onset AF.

Results: AF incidence increased from 0.9 per 1000 person-years at baseline age 40-49 years, to 17.7 at baseline age ≥70 years. Multivariable-adjusted Cox models showed that higher BMI, hypertension, high alcohol consumption and a history of stroke or MI were associated with increased risk of AF across age groups (p<0.05). Between 30% and 40% of the AF risk could be attributed to BMI, hypertension and a history of stroke or MI. New-onset AF was associated with a twofold increase in risk of stroke and death at ages≥70 years (p≤0.001).

Conclusion: In this large European cohort aged 40 years and above, risk of AF was largely attributed to BMI, high alcohol consumption and a history MI or stroke from middle age. Thus, preventive measures for AF should target risk factors such as obesity and hypertension from early age and continue throughout life.
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http://dx.doi.org/10.1136/openhrt-2021-001624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330568PMC
July 2021

World Heart Federation Roadmap on Atrial Fibrillation - A 2020 Update.

Glob Heart 2021 05 27;16(1):41. Epub 2021 May 27.

Universidad de Buenos Aires, AR.

The World Heart Federation (WHF) commenced a Roadmap initiative in 2015 to reduce the global burden of cardiovascular disease and resultant burgeoning of healthcare costs. Roadmaps provide a blueprint for implementation of priority solutions for the principal cardiovascular diseases leading to death and disability. Atrial fibrillation (AF) is one of these conditions and is an increasing problem due to ageing of the world's population and an increase in cardiovascular risk factors that predispose to AF. The goal of the AF roadmap was to provide guidance on priority interventions that are feasible in multiple countries, and to identify roadblocks and potential strategies to overcome them. Since publication of the AF Roadmap in 2017, there have been many technological advances including devices and artificial intelligence for identification and prediction of unknown AF, better methods to achieve rhythm control, and widespread uptake of smartphones and apps that could facilitate new approaches to healthcare delivery and increasing community AF awareness. In addition, the World Health Organisation added the non-vitamin K antagonist oral anticoagulants (NOACs) to the Essential Medicines List, making it possible to increase advocacy for their widespread adoption as therapy to prevent stroke. These advances motivated the WHF to commission a 2020 AF Roadmap update. Three years after the original Roadmap publication, the identified barriers and solutions were judged still relevant, and progress has been slow. This 2020 Roadmap update reviews the significant changes since 2017 and identifies priority areas for achieving the goals of reducing death and disability related to AF, particularly targeted at low-middle income countries. These include advocacy to increase appreciation of the scope of the problem; plugging gaps in guideline management and prevention through physician education, increasing patient health literacy, and novel ways to increase access to integrated healthcare including mHealth and digital transformations; and greater emphasis on achieving practical solutions to national and regional entrenched barriers. Despite the advances reviewed in this update, the task will not be easy, but the health rewards of implementing solutions that are both innovative and practical will be great.
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http://dx.doi.org/10.5334/gh.1023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162289PMC
May 2021

[Atrial fibrillation].

Internist (Berl) 2021 Jun 29. Epub 2021 Jun 29.

Klinik und Poliklinik für Kardiologie, Universitäres Herz- und Gefäßzentrum UKE Hamburg, Martinistraße 52, 20246, Hamburg, Deutschland.

Atrial fibrillation is frequent and has severe sequelae, such as stroke, cardiovascular death and cardiac insufficiency. These sequelae can be effectively reduced by anticoagulants, a meticulous recognition and treatment of cardiovascular comorbidities and an early rhythm-preserving treatment. Catheter ablation leads to a better preservation of the sinus rhythm and in symptomatic patients to a better quality of life in comparison to treatment with antiarrhythmic agents. This should be included in the planning of early rhythm-maintaining treatment.
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http://dx.doi.org/10.1007/s00108-021-01067-0DOI Listing
June 2021

Genetic and Clinical Predictors of Left Atrial Thrombus: A Single Center Case-Control Study.

Clin Appl Thromb Hemost 2021 Jan-Dec;27:10760296211021171

Department of Cardiology, University Heart and Vascular Center, Hamburg, Germany.

Left atrial (LA) thrombus formation is the presumed origin of thromboembolic complications in patients with atrial fibrillation (AF). Beyond clinical risk factors, the factors causing formation of LA thrombi are not well known. In this case-control study, we analyzed clinical characteristics and genetic thrombophilia markers (factor V Leiden (FVL), prothrombin G20210A (FIIV), Tyr2561 variant of von Willebrand factor (VWF-V)) in 42 patients with AF and LA thrombus (LAT) and in 68 control patients with AF without LAT (CTR). Patients with LAT had more clinical conditions predisposing to stroke (mean CHADS-VASc-score 3.4 ± 1.5 vs. 1.9 ± 1.4; < 0.001), a higher LA volume (96 ± 32 vs. 76 ± 21 ml, = 0.002) and lower LA appendage emptying velocity (0.21 ± 0.11vs. 0.43 ± 0.19 m/s, < 0.001). Prevalence of FVL, FIIV and VWF-V mutations was not different, but in the subgroup of patients <65 years (y) there was a tendency for a higher incidence of VWF-V with a prevalence of 27% (LAT <65 y) vs. 7% (CTR <65 y, = 0.066). These findings warrant further investigation of the VWF-V as a risk factor for LA thrombogenesis in younger patients.
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http://dx.doi.org/10.1177/10760296211021171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246465PMC
June 2021

Mobile health for walking on the tightrope of optimal physical activity to reduce the risk of atrial fibrillation.

Eur Heart J 2021 07;42(25):2484-2486

Department of Cardiology, University Heart and Vascular Center Hamburg Eppendorf, Hamburg, Germany.

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http://dx.doi.org/10.1093/eurheartj/ehab243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248993PMC
July 2021

Expert opinion paper on cardiac imaging after ischemic stroke.

Clin Res Cardiol 2021 Jul 18;110(7):938-958. Epub 2021 Jun 18.

Atrial Fibrillation NETwork (AFNET) e.V., Münster, Germany.

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.
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http://dx.doi.org/10.1007/s00392-021-01834-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238761PMC
July 2021

[Cardiac diagnostics after ischemic stroke or transitory ischemic attack].

Dtsch Med Wochenschr 2021 Jun 15;146(12):801-808. Epub 2021 Jun 15.

Stroke is the most common cause of permanent disability and one of the most common causes of death. Cardio-embolic strokes are associated with a poor prognosis and a high risk of recurrence compared to other stroke etiologies. The most common source of cardiac embolism is atrial fibrillation which must be quickly identified to optimize secondary stroke prevention. A structured evaluation after ischemic stroke includes taking the medical history, a physical examination, 12-lead ECG recording, rhythm monitoring for 72 h, transthoracic echocardiography and transesophageal echocardiography, if an atrial embolic source of stroke is suspected. Extended cardiac work-up (e. g., MRI/CT, prolonged rhythm monitoring) should be performed in selected patients based on diagnostic findings.
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http://dx.doi.org/10.1055/a-1221-7095DOI Listing
June 2021

Reclassification, Thromboembolic, and Major Bleeding Outcomes Using Different Estimates of Renal Function in Anticoagulated Patients With Atrial Fibrillation: Insights From the PREFER-in-AF and PREFER-in-AF Prolongation Registries.

Circ Cardiovasc Qual Outcomes 2021 Jun 3;14(6):e006852. Epub 2021 Jun 3.

Chair of Cardiology, University of Pisa and Cardiology Division, Pisa University Hospital, Italy (R.D.C.).

Background: The Cockcroft-Gault formula is recommended to determine a renal indication for dose reduction of dabigatran, edoxaban, and rivaroxaban. Nephrology guidelines now recommend the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulae as more accurate estimates of glomerular filtration rate.

Methods: We analyzed anticoagulated patients with atrial fibrillation who were enrolled in the Prevention of Thromboembolic Events - European Registry in Atrial Fibrillation (PREFER in AF). The proportion of patients with dissimilar renal dosing indications was assessed when applying Cockcroft-Gault, MDRD, or CKD-EPI. Thromboembolic and major bleeding events at 1 year were compared in patients in whom Cockcroft-Gault and CKD-EPI provided concordant or discordant results around a threshold of 50 mL/minute.

Results: Out of 1288 patients with atrial fibrillation with chronic kidney disease in whom Cockcroft-Gault suggested a dose reduction of dabigatran, edoxaban, or rivaroxaban (creatinine clearance ≤50 mL/minutes), 19% and 16% were reclassified to the respective higher doses, and 24% and 23% to the respective lower doses by applying the MDRD and CKD-EPI formulae, respectively. In patients potentially receiving a different dose of dabigatran, edoxaban, or rivaroxaban when using CKD-EPI, we observed an excess of thromboembolic events (4.1% versus 0.8%; odds ratio, 5.5 [95% CI, 1.5-20.8]; =0.01). Major bleeding rates were nonsignificantly different in the discordance versus concordance group (5.7% versus 2.7%; odds ratio, 2.2 [95% CI, 0.9-5.6]; =0.09).

Conclusions: The MDRD and CKD-EPI formulae suggest a different dosing in up to a quarter of anticoagulated patients with atrial fibrillation. This seems to impact hard outcomes.
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http://dx.doi.org/10.1161/CIRCOUTCOMES.120.006852DOI Listing
June 2021

The Association of Periodontitis and Peripheral Arterial Occlusive Disease in a Prospective Population-Based Cross-Sectional Cohort Study.

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

Department of Vascular Medicine, University Heart and Vascular Center UKE Hamburg, Research Group GermanVasc, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.

Objectives: Peripheral arterial occlusive disease (PAOD) and periodontitis are common chronic diseases, which together affect almost 1 billion people worldwide. There is growing evidence suggesting a relationship between chronic inflammatory conditions such as periodontitis and PAOD. This study aims to determine an association between both entities using high quality research data and multiple phenotypes derived from an epidemiological cohort study.

Design: This population-based cross-sectional cohort study included data from 3271 participants aged between 45 and 74 years enrolled in the Hamburg City Health Study (NCT03934957).

Material & Methods: An ankle-brachial-index below 0.9, color-coded ultrasound of the lower extremity arteries, and survey data was used to identify participants with either asymptomatic or symptomatic PAOD. Periodontitis data was collected at six sites per tooth and included the probing depth, gingival recession, clinical attachment loss, and bleeding on probing index. Multivariate analyses using logistic regression models were adjusted for variables including age, sex, smoking, education, diabetes, and hypertension.

Results: The baseline characteristics differed widely between participants neither affected by periodontitis nor PAOD vs. the group where both PAOD and severe periodontitis were identified. A higher rate of males, higher age, lower education level, smoking, diabetes, and cardiovascular disease was observed in the group affected by both diseases. After adjusting, presence of severe periodontitis (odds ratio 1.265; 97.5% CI 1.006-1.591; = 0.045) was independently associated with PAOD.

Conclusion: In this cross-sectional analysis of a prospective cohort study, an independent association between periodontitis and PAOD was revealed. The results of the current study emphasize a potential for preventive medicine in an extremely sensitive target population. Future studies should determine the underlying factors modifying the relationship between both diseases.
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http://dx.doi.org/10.3390/jcm10102048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152001PMC
May 2021

Genetics of atrial fibrillation-practical applications for clinical management: if not now, when and how?

Cardiovasc Res 2021 Jun;117(7):1718-1731

Department of Cardiology, University Heart and Vascular Center, University Medical Center Hamburg Eppendorf, Martinistraße 52, 20251 Hamburg, Hamburg, Germany.

The prevalence and economic burden of atrial fibrillation (AF) are predicted to more than double over the next few decades. In addition to anticoagulation and treatment of concomitant cardiovascular conditions, early and standardized rhythm control therapy reduces cardiovascular outcomes as compared with a rate control approach, favouring the restoration, and maintenance of sinus rhythm safely. Current therapies for rhythm control of AF include antiarrhythmic drugs (AADs) and catheter ablation (CA). However, response in an individual patient is highly variable with some remaining free of AF for long periods on antiarrhythmic therapy, while others require repeat AF ablation within weeks. The limited success of rhythm control therapy for AF is in part related to incomplete understanding of the pathophysiological mechanisms and our inability to predict responses in individual patients. Thus, a major knowledge gap is predicting which patients with AF are likely to respond to rhythm control approach. Over the last decade, tremendous progress has been made in defining the genetic architecture of AF with the identification of rare mutations in cardiac ion channels, signalling molecules, and myocardial structural proteins associated with familial (early-onset) AF. Conversely, genome-wide association studies have identified common variants at over 100 genetic loci and the development of polygenic risk scores has identified high-risk individuals. Although retrospective studies suggest that response to AADs and CA is modulated in part by common genetic variation, the development of a comprehensive clinical and genetic risk score may enable the translation of genetic data to the bedside care of AF patients. Given the economic impact of the AF epidemic, even small changes in therapeutic efficacy may lead to substantial improvements for patients and health care systems.
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http://dx.doi.org/10.1093/cvr/cvab153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208749PMC
June 2021

Alcohol and atrial fibrillation: dose matters, not so much the type.

Eur Heart J 2021 07;42(25):2507-2508

Department of Cardiology, University Heart & Vascular Center Hamburg, Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.

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http://dx.doi.org/10.1093/eurheartj/ehab180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248995PMC
July 2021

Sex differences in patients with cardiogenic shock.

ESC Heart Fail 2021 06 24;8(3):1775-1783. Epub 2021 Mar 24.

Department of Cardiology, University Heart and Vascular Center Hamburg, Martinistraße 52, Hamburg, 20246, Germany.

Aims: Differences between female and male patients in clinical presentation, causes and treatment of cardiogenic shock (CS) are poorly understood. We aimed to investigate sex differences in presentation with and treatment of CS.

Methods And Results: We analysed data of 978 patients presenting with CS to a tertiary care hospital between October 2009 and October 2017. Multivariable adjusted logistic/Cox regression models were fitted to investigate the association between sex and clinical presentation, use of treatments and 30 day mortality. Median age was 70 years (interquartile range 58-79 years), and 295 (30.2%) patients were female. After adjustment for multiple relevant confounders, female patients were more likely to be older [odds ratio (OR) 1.21, 95% confidence interval (CI) 1.02-1.42, P = 0.027], but other relevant presentation characteristics did not differ between both sexes. Despite the similar presentation, female patients were less likely to be treated with percutaneous left ventricular assist devices (OR 0.78, 95% CI 0.64-0.94, P = 0.010), but more likely to be treated with catecholamines (OR 1.21, 95% CI 1.02-1.44, P = 0.033) or vasopressors (OR 1.26, 95% CI 1.05-1.50, P = 0.012). A 30 day mortality risk in female patients was as high as in male patients (hazard ratio 1.08, 95% CI 1.00-1.18, P = 0.091).

Conclusions: In this large, contemporary cohort, clinical presentation was comparable in female and male patients, and both sexes were associated with a comparably high mortality risk. Nevertheless, female patients received different treatment for CS and were most importantly less likely to be treated with percutaneous left ventricular assist devices.
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http://dx.doi.org/10.1002/ehf2.13303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120358PMC
June 2021

Noninvasive peripheral vascular function, incident cardiovascular disease, and mortality in the general population.

Cardiovasc Res 2021 Mar 16. Epub 2021 Mar 16.

Center for Thrombosis and Hemostasis, University Medical Center Mainz, Germany (PSW); Center for Cardiology-, Cardiology I (VHS, NA, AL, TG, TM).

Aims: Evidence suggests that peripheral vascular function is related to cardiovascular disease (CVD) and mortality. We evaluated the associations of noninvasive measures of flow-mediated dilatation and peripheral arterial tonometry with incident CVD and mortality.

Methods And Results: In a post-hoc analysis of the community-based Gutenberg Health Study, median age 55 years (25th/75th percentile 46/65) and 49.5% women, we measured brachial artery flow-mediated dilatation (N = 12,599) and fingertip peripheral arterial tonometry (N = 11,125). After a follow-up of up to 11.7 years, we observed 595 incident CVD events, 106 cardiac deaths, and 860 deaths in total. Survival curves showed decreased event-free survival with higher mean brachial artery diameter and baseline pulse amplitude and better survival with higher mean flow-mediated dilatation and peripheral arterial tonometry ratio (all Plog rank<0.05). In multivariable-adjusted Cox regression analyses only baseline pulse amplitude was inversely related to mortality ((hazard ratio) per standard deviation increase, 0.86, 95% confidence interval, 0.79-0.94; P = 0.0009). After exclusion of individuals with prevalent cardiovascular disease the association was no longer statistically significant in multivariable-adjusted models (hazard ratio 0.91, 95% confidence interval 0.81-1.02; P = 0.11). None of the vascular variables substantially increased the C-index of a model comprising clinical risk factors.

Conclusions: In our cohort, noninvasive measures of peripheral vascular structure and function did not reveal clinically relevant associations with incident cardiovascular disease or mortality. Whether determination of pulse amplitude by peripheral arterial tonometry improves clinical decision-making in primary prevention needs to be demonstrated.

Translational Perspective: In our large middle-aged community cohort with more than 15,000 individuals, median age 55 years (25th/75th percentile 46/65), 49.5% women noninvasively measured peripheral vascular function using flow-mediated dilation after upper arm occlusion or fingertip peripheral arterial tonometry was not relevantly associated with incident cardiovascular disease or mortality in multivariable-adjusted analyses. An interaction of the association of peripheral arterial tonometry with mortality by prevalent cardiovascular disease was observed. Routine measurement of flow-mediated dilation or peripheral arterial tonometry in our community cohort to screen for high risk of cardiovascular disease or mortality was not effective.
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http://dx.doi.org/10.1093/cvr/cvab087DOI Listing
March 2021

Clinical Factors Associated with Atrial Fibrillation Detection on Single-Time Point Screening Using a Hand-Held Single-Lead ECG Device.

J Clin Med 2021 Feb 12;10(4). Epub 2021 Feb 12.

Heart Research Institute, Charles Perkins Centre, and Concord Hospital Cardiology, University of Sydney, Sydney 2006, Australia.

Our aim was to assess the prevalence of unknown atrial fibrillation (AF) among adults during single-time point rhythm screening performed during meetings or social recreational activities organized by patient groups or volunteers. A total of 2814 subjects (median age 68 years) underwent AF screening by a handheld single-lead ECG device (MyDiagnostick). Overall, 56 subjects (2.0%) were diagnosed with AF, as a result of 12-lead ECG following a positive/suspected recording. Screening identified AF in 2.9% of the subjects ≥ 65 years. None of the 265 subjects aged below 50 years was found positive at AF screening. Risk stratification for unknown AF based on a CHADSVASc > 0 in males and >1 in females (or CHADSVA > 0) had a high sensitivity (98.2%) and a high negative predictive value (99.8%) for AF detection. A slightly lower sensitivity (96.4%) was achieved by using age ≥ 65 years as a risk stratifier. Conversely, raising the threshold at ≥75 years showed a low sensitivity. Within the subset of subjects aged ≥ 65 a CHADSVASc > 1 in males and >2 in females, or a CHADSVA > 1 had a high sensitivity (94.4%) and negative predictive value (99.3%), while age ≥ 75 was associated with a marked drop in sensitivity for AF detection.
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http://dx.doi.org/10.3390/jcm10040729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917757PMC
February 2021

Atrial fibrillation: villain or bystander in vascular brain injury.

Eur Heart J Suppl 2020 Nov 6;22(Suppl M):M51-M59. Epub 2020 Dec 6.

University Heart and Vascular Centre, Department of Cardiology, Hamburg, Germany; German Centre for Cardiovascular Research (DZHK e.V.), partner site Hamburg/Kiel/Lübeck, Hamburg, Germany.

Atrial fibrillation (AF) and stroke are inextricably connected, with classical Virchow pathophysiology explaining thromboembolism through blood stasis in the fibrillating left atrium. This conceptualization has been reinforced by the remarkable efficacy of oral anticoagulant (OAC) for stroke prevention in AF. A number of observations showing that the presence of AF is neither necessary nor sufficient for stroke, cast doubt on the causal role of AF as a villain in vascular brain injury (VBI). The requirement for additional risk factors before AF increases stroke risk; temporal disconnect of AF from a stroke in patients with no AF for months before stroke during continuous ECG monitoring but manifesting AF only after stroke; and increasing recognition of the role of atrial cardiomyopathy and atrial substrate in AF-related stroke, and also stroke without AF, have led to rethinking the pathogenetic model of cardioembolic stroke. This is quite separate from recognition that in AF, shared cardiovascular risk factors can lead both to non-embolic stroke, or emboli from the aorta and carotid arteries. Meanwhile, VBI is now expanded to include dementia and cognitive decline: research is required to see if reduced by OAC. A changed conceptual model with less focus on the arrhythmia, and more on atrial substrate/cardiomyopathy causing VBI both in the presence or absence of AF, is required to allow us to better prevent AF-related VBI. It could direct focus towards prevention of the atrial cardiomyopathy though much work is required to better define this entity before the balance between AF as villain or bystander can be determined.
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http://dx.doi.org/10.1093/eurheartj/suaa166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916423PMC
November 2020

Digital, risk-based screening for atrial fibrillation in the European community-the AFFECT-EU project funded by the European Union.

Eur Heart J 2021 07;42(27):2625-2627

Department of Cardiology, University Heart and Vascular Center Hamburg Eppendorf, Hamburg, Germany.

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http://dx.doi.org/10.1093/eurheartj/ehab050DOI Listing
July 2021

Non-immune risk predictors of cardiac allograft vasculopathy: Results from the U.S. organ procurement and transplantation network.

Int J Cardiol 2021 05 9;331:57-62. Epub 2021 Feb 9.

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

Background: Cardiac allograft vasculopathy (CAV) remains a major long-term complication in heart transplant (HT) recipients related to increased mortality. We aimed to identify non-immune recipient- and donor-related risk factors for the development of CAV in HT patients.

Methods: 40,647 recipients, prospectively enrolled from April 1995 to January 2019 in the Organ Procurement and Transplantation Network (OPTN), were analyzed after exclusion of pediatric patients, those with missing information on CAV, and re-transplantation. Multivariable-adjusted Cox regression analyses were performed to identify recipient- and donor-related risk factors for CAV. 5-year population attributable risk for classical cardiovascular risk factors was calculated to estimate the recipients' CAV risk. Analyses were based on OPTN data (June 30, 2019).

Results: Of 40,647 post-transplant patients, 14,698 (36.2%) developed CAV with a higher incidence in males (37.3%) than in females (32.6%) (p < 0.001). The mean follow-up time was 68.2 months. In recipients, male sex, African American and Asian ethnicity, ischemic cardiomyopathy, body mass index and smoking were associated with CAV occurrence. In donors, older age, male sex, smoking, diabetes and arterial hypertension were related to CAV. Results remained fairly stable after analysis of different time periods. 5-year attributable CAV risk for classical cardiovascular risk factors was 9.1%.

Conclusions: In this large registry with known limitations concerning data completeness, CAV incidence was higher in males than in females. Next to male sex and donor age, the classical cardiovascular risk factors were related to incident CAV. Classical cardiovascular risk factors played only a minor role for the 5-year attributable CAV risk.
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http://dx.doi.org/10.1016/j.ijcard.2021.02.002DOI Listing
May 2021

Dynamic risk assessment to improve quality of care in patients with atrial fibrillation: the 7th AFNET/EHRA Consensus Conference.

Europace 2021 03;23(3):329-344

Atrial Fibrillation NETwork (AFNET), Münster, Germany.

Aims: The risk of developing atrial fibrillation (AF) and its complications continues to increase, despite good progress in preventing AF-related strokes.

Methods And Results: This article summarizes the outcomes of the 7th Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA) held in Lisbon in March 2019. Sixty-five international AF specialists met to present new data and find consensus on pressing issues in AF prevention, management and future research to improve care for patients with AF and prevent AF-related complications. This article is the main outcome of an interactive, iterative discussion between breakout specialist groups and the meeting plenary. AF patients have dynamic risk profiles requiring repeated assessment and risk-based therapy stratification to optimize quality of care. Interrogation of deeply phenotyped datasets with outcomes will lead to a better understanding of the cardiac and systemic effects of AF, interacting with comorbidities and predisposing factors, enabling stratified therapy. New proposals include an algorithm for the acute management of patients with AF and heart failure, a call for a refined, data-driven assessment of stroke risk, suggestions for anticoagulation use in special populations, and a call for rhythm control therapy selection based on risk of AF recurrence.

Conclusion: The remaining morbidity and mortality in patients with AF needs better characterization. Likely drivers of the remaining AF-related problems are AF burden, potentially treatable by rhythm control therapy, and concomitant conditions, potentially treatable by treating these conditions. Identifying the drivers of AF-related complications holds promise for stratified therapy.
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http://dx.doi.org/10.1093/europace/euaa279DOI Listing
March 2021

Heart and brain interactions : Pathophysiology and management of cardio-psycho-neurological disorders.

Herz 2021 Mar 5;46(2):138-149. Epub 2021 Feb 5.

Deutsches Zentrum für Herzinsuffizienz, Universität und Universitätsklinikum Würzburg, Am Schwarzenberg 15, 97078, Würzburg, Germany.

Cardiovascular diseases (CVD) and mental health disorders (MHD; e.g. depression, anxiety and cognitive dysfunction) are highly prevalent and are associated with significant morbidity and mortality and impaired quality of life. Currently, possible interactions between pathophysiological mechanisms in MHD and CVD are rarely considered during the diagnostic work-up, prognostic assessment and treatment planning in patients with CVD, and research addressing bidirectional disease mechanisms in a systematic fashion is scarce. Besides some overarching pathogenetic principles shared by CVD and MHD, there are specific syndromes in which pre-existing neurological or psychiatric illness predisposes and contributes to CVD development (as in Takotsubo syndrome), or in which the distorted interplay between innate immune and central nervous systems and/or pre-existing CVD leads to secondary MHD and brain damage (as in peripartum cardiomyopathy or atrial fibrillation). Clinical manifestations and phenotypes of cardio-psycho-neurological diseases depend on the individual somatic, psychosocial, and genetic risk profile as well as on personal resilience, and differ in many respects between men and women. In this article, we provide arguments on why, in such conditions, multidisciplinary collaborations should be established to allow for more comprehensive understanding of the pathophysiology as well as appropriate and targeted diagnosis and treatment. In addition, we summarize current knowledge on the complex interactions between the cardiovascular and central nervous systems in Takotsubo syndrome and peripartum cardiomyopathy, and on the neurological and psychiatric complications of atrial fibrillation.
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http://dx.doi.org/10.1007/s00059-021-05022-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966144PMC
March 2021

Research Priorities in Atrial Fibrillation Screening: A Report From a National Heart, Lung, and Blood Institute Virtual Workshop.

Circulation 2021 Jan 25;143(4):372-388. Epub 2021 Jan 25.

Division of Cardiology and Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (R.D.L., J.P.P., S.M.A.-K.).

Clinically recognized atrial fibrillation (AF) is associated with higher risk of complications, including ischemic stroke, cognitive decline, heart failure, myocardial infarction, and death. It is increasingly recognized that AF frequently is undetected until complications such as stroke or heart failure occur. Hence, the public and clinicians have an intense interest in detecting AF earlier. However, the most appropriate strategies to detect undiagnosed AF (sometimes referred to as subclinical AF) and the prognostic and therapeutic implications of AF detected by screening are uncertain. Our report summarizes the National Heart, Lung, and Blood Institute's virtual workshop focused on identifying key research priorities related to AF screening. Global experts reviewed major knowledge gaps and identified critical research priorities in the following areas: (1) role of opportunistic screening; (2) AF as a risk factor, risk marker, or both; (3) relationship between AF burden detected with long-term monitoring and outcomes/treatments; (4) designs of potential randomized trials of systematic AF screening with clinically relevant outcomes; and (5) role of AF screening after ischemic stroke. Our report aims to inform and catalyze AF screening research that will advance innovative, resource-efficient, and clinically relevant studies in diverse populations to improve the diagnosis, management, and prognosis of patients with undiagnosed AF.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.047633DOI Listing
January 2021

Risk prediction of atrial fibrillation in the community combining biomarkers and genetics.

Europace 2021 05;23(5):674-681

Department of Cardiology, University Heart and Vascular Centre Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.

Aims: Classical cardiovascular risk factors (CVRFs), biomarkers, and common genetic variation have been suggested for risk assessment of atrial fibrillation (AF). To evaluate their clinical potential, we analysed their individual and combined ability of AF prediction.

Methods And Results: In N = 6945 individuals of the FINRISK 1997 cohort, we assessed the predictive value of CVRF, N-terminal pro B-type natriuretic peptide (NT-proBNP), and 145 recently identified single-nucleotide polymorphisms (SNPs) combined in a developed polygenic risk score (PRS) for incident AF. Over a median follow-up of 17.8 years, n = 551 participants (7.9%) developed AF. In multivariable-adjusted Cox proportional hazard models, NT-proBNP [hazard ratio (HR) of log transformed values 4.77; 95% confidence interval (CI) 3.66-6.22; P < 0.001] and the PRS (HR 2.18; 95% CI 1.88-2.53; P < 0.001) were significantly related to incident AF. The discriminatory ability improved asymptotically with increasing numbers of SNPs. Compared with a clinical model, AF risk prediction was significantly improved by addition of NT-proBNP and the PRS. The C-statistic for the combination of CVRF, NT-proBNP, and the PRS reached 0.83 compared with 0.79 for CVRF only (P < 0.001). A replication in the Dutch Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort revealed similar results. Comparing the highest vs. lowest quartile, NT-proBNP and the PRS both showed a more than three-fold increased AF risk. Age remained the strongest risk factor with a 16.7-fold increased risk of AF in the highest quartile.

Conclusion: The PRS and the established biomarker NT-proBNP showed comparable predictive ability. Both provided incremental predictive value over standard clinical variables. Further improvements for the PRS are likely with the discovery of additional SNPs.
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http://dx.doi.org/10.1093/europace/euaa334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139818PMC
May 2021

Alcohol consumption, cardiac biomarkers, and risk of atrial fibrillation and adverse outcomes.

Eur Heart J 2021 03;42(12):1170-1177

Department of Cardiology, University Heart & Vascular Center Hamburg, Martinistraße 52, 20246 Hamburg, Germany.

Aims: There is inconsistent evidence on the relation of alcohol intake with incident atrial fibrillation (AF), in particular at lower doses. We assessed the association between alcohol consumption, biomarkers, and incident AF across the spectrum of alcohol intake in European cohorts.

Methods And Results: In a community-based pooled cohort, we followed 107 845 individuals for the association between alcohol consumption, including types of alcohol and drinking patterns, and incident AF. We collected information on classical cardiovascular risk factors and incident heart failure (HF) and measured the biomarkers N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin I. The median age of individuals was 47.8 years, 48.3% were men. The median alcohol consumption was 3 g/day. N = 5854 individuals developed AF (median follow-up time: 13.9 years). In a sex- and cohort-stratified Cox regression analysis alcohol consumption was non-linearly and positively associated with incident AF. The hazard ratio for one drink (12 g) per day was 1.16, 95% CI 1.11-1.22, P < 0.001. Associations were similar across types of alcohol. In contrast, alcohol consumption at lower doses was associated with reduced risk of incident HF. The association between alcohol consumption and incident AF was neither fully explained by cardiac biomarker concentrations nor by the occurrence of HF.

Conclusions: In contrast to other cardiovascular diseases such as HF, even modest habitual alcohol intake of 1.2 drinks/day was associated with an increased risk of AF, which needs to be considered in AF prevention.
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http://dx.doi.org/10.1093/eurheartj/ehaa953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982286PMC
March 2021

Intravascular Lithotripsy for the Treatment of Calcium-Mediated Coronary In-Stent Restenoses.

J Invasive Cardiol 2021 Jan;33(1):E25-E31

University Heart & Vascular Center, Department of Cardiology, Hamburg, Germany.

Background: Coronary intravascular lithotripsy (IVL) has recently been evaluated for the treatment of severely calcified native coronary lesions. Evidence for its use in in-stent restenosis is sparse and is still an off-label indication. Therefore, we aimed to evaluate the feasibility, safety, and acute and mid-term angiographic outcomes after IVL for the treatment of calcium-mediated coronary in-stent restenosis.

Methods: A retrospective, single-center analysis was performed for 6 cases with undilatable instent restenosis due to calcium-mediated stent underexpansion and/ or calcified neointima from January to November 2019. Lesions were treated with IVL (Shockwave Medical) and subsequent drug-eluting stent or drug-coated balloon. Angiographic success was defined as residual lumen stenosis <20% and Thrombolysis in Myocardial Infarction 3 flow. Follow-up angiography was performed at a median of 141.5 days.

Results: Six patients presented with symptomatic in-stent restenoses (65.8% to 87.9%) at 11 to 175 months after implantation. Intravascular and angiographic imaging detected calcium-mediated stent underexpansion (n = 2), calcified neointima (n = 2), or a combination of both (n = 2) as cause of restenosis. In-stent IVL, subsequent high-pressure balloon dilation, and drug-eluting stent or drug-coated balloon implantation were performed successfully in all cases. Acute angiographic success and angina relief were achieved in 5 of 6 cases and sustained during follow-up. No major acute cardiovascular events occurred.

Conclusions: The application of IVL for the treatment of calcium-mediated coronary in-stent restenosis was feasible and safe, and yielded promising short- and mid-term results in the majority of cases.
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January 2021

Diversity 4.0 in the cardiovascular health-care workforce.

Nat Rev Cardiol 2020 Dec;17(12):751-753

Boston University and National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA, USA.

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http://dx.doi.org/10.1038/s41569-020-00462-8DOI Listing
December 2020
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