Journal: Clin Res Cardiol

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Abstract

Fractional flow reserve in patients with coronary artery disease undergoing TAVI: a prospective analysis.

Stundl A, Shamekhi J, Bernhardt S, Starke M, ... Werner N, Sinning JM
Objectives
To determine the true prevalence of CAD in AS patients, to detect changes of the hemodynamic significance of coronary lesions following TAVI, to explore to what extent FFR-positive CAD might influence outcome and finally to develop a management algorithm for this patient subset.
Methods
From May 2016 to March 2018, diagnostic coronary angiography was performed in 246 patients before TAVI. In the presence of coronary lesions with a diameter stenosis ≥ 50%, FFR was measured. In patients with positive FFR ≤ 0.80, a control angiography was performed 6-8 weeks after TAVI.
Results
The study cohort was 81.0 ± 6.1 years old, 48.4% of the patients were male. 53.3% had concomitant CAD. 35.9% of these patients underwent PCI before TAVI due to functionally significant left main CAD and/or severe stenosis ≥ 90%. 31 patients underwent FFR measurements in cumulative 38 coronary lesions. Prior to TAVI, a negative FFR could be detected in 18 lesions, whereas a positive FFR was found in entirely 20 lesions. A control angiography and FFR measurement was performed in cumulative 13 lesions. Comparing the FFR values, there was no significant difference (0.77 ± 0.04 vs. 0.76 ± 0.08; p = 0.11).
Conclusion
Concomitant CAD was diagnosed in 53.3% of TAVI patients. FFR did not significantly change after TAVI, confirming the validity of FFR to evaluate coronary lesions in this specific clinical setting. Given the low rates of cardiac adverse events, it might therefore be considered to treat coronary stenoses not involving left main and those with a diameter stenosis < 90% after TAVI.



Clin Res Cardiol: 01 Nov 2019; epub ahead of print
Stundl A, Shamekhi J, Bernhardt S, Starke M, ... Werner N, Sinning JM
Clin Res Cardiol: 01 Nov 2019; epub ahead of print | PMID: 31679046
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Abstract

Thrombus aspiration in patients with ST-elevation myocardial infarction presenting late after symptom onset: long-term clinical outcome of a randomized trial.

Freund A, Schock S, Stiermaier T, de Waha-Thiele S, ... Thiele H, Desch S
Background
In the largest randomized trial so far, thrombus aspiration failed to reduce the primary endpoint of microvascular obstruction (MVO) in patients with ST-elevation myocardial infarction (STEMI) presenting late after symptom onset. Long-term clinical outcome data of this trial have not been reported yet.
Methods and results
A total of 144 patients with STEMI presenting ≥ 12 and ≤ 48 h after symptom onset were randomized to primary percutaneous coronary intervention (PCI) with or without manual thrombus aspiration in a 1:1 fashion. The primary efficacy endpoint was the extent of MVO assessed by cardiac magnetic resonance imaging and showed no significant difference between groups. Long-term clinical follow-up was performed at 4 years. Overall mortality at 4 years reached 18%. There was no significant difference between groups with respect to mortality and major adverse cardiac events defined as the composite of death, myocardial reinfarction and target vessel revascularization. In a multivariate Cox regression model glomerular filtration rate on admission, left ventricular ejection fraction, and cardiogenic shock were independently associated with time-dependent occurrence of death.
Conclusion
Routine thrombus aspiration in STEMI patients presenting late after symptom onset showed no significant difference with respect to long-term clinical endpoints compared to conventional PCI only.



Clin Res Cardiol: 30 Oct 2019; 108:1208-1214
Freund A, Schock S, Stiermaier T, de Waha-Thiele S, ... Thiele H, Desch S
Clin Res Cardiol: 30 Oct 2019; 108:1208-1214 | PMID: 30859380
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Abstract

Clinical and genetic insights into non-compaction: a meta-analysis and systematic review on 7598 individuals.

Kayvanpour E, Sedaghat-Hamedani F, Gi WT, Tugrul OF, ... Katus HA, Meder B
Background
Left ventricular non-compaction has been increasingly diagnosed in recent years. However, it is still debated whether non-compaction is a pathological condition or a physiological trait. In this meta-analysis and systematic review, we compare studies, which investigated these two different perspectives. Furthermore, we provide a comprehensive overview on the clinical outcome as well as genetic background of left ventricular non-compaction cardiomyopathy in adult patients.
Methods and results
We retrieved PubMed/Medline literatures in English language from 2000 to 19/09/2018 on clinical outcome and genotype of patients with non-compaction. We summarized and extensively reviewed all studies that passed selection criteria and performed a meta-analysis on key phenotypic parameters. Altogether, 35 studies with 2271 non-compaction patients were included in our meta-analysis. The mean age at diagnosis was the mid of their fifth decade. Two-thirds of patients were male. Congenital heart diseases including atrial or ventricular septum defect or Ebstein anomaly were reported in 7% of patients. Twenty-four percent presented with family history of cardiomyopathy. The mean frequency of neuromuscular diseases was 5%. Heart rhythm abnormalities were reported frequently: conduction disease in 26%, supraventricular tachycardia in 17%, and sustained or non-sustained ventricular tachycardia in 18% of patients. Three important outcome measures were reported including systemic thromboembolic events with a mean frequency of 9%, heart transplantation with 4%, and adequate ICD therapy with 15%. Nine studies investigated the genetics of non-compaction cardiomyopathy. The most frequently mutated gene was TTN with a pooled frequency of 11%. The average frequency of MYH7 mutations was 9%, for MYBPC3 mutations 5%, and for CASQ2 and LDB3 3% each. TPM1, MIB1, ACTC1, and LMNA mutations had an average frequency of 2% each. Mutations in PLN, HCN4, TAZ, DTNA, TNNT2, and RBM20 were reported with a frequency of 1% each. We also summarized the results of eight studies investigating the non-compaction in altogether 5327 athletes, pregnant women, patients with sickle cell disease, as well as individuals from population-based cohorts, in which the presence of left ventricular hypertrabeculation ranged from 1.3 to 37%.
Conclusion
The summarized data indicate that non-compaction may lead to unfavorable outcome in different cardiomyopathy entities. The presence of key features in a multimodal diagnostic approach could distinguish between benign morphological trait and manifest cardiomyopathy.



Clin Res Cardiol: 30 Oct 2019; 108:1297-1308
Kayvanpour E, Sedaghat-Hamedani F, Gi WT, Tugrul OF, ... Katus HA, Meder B
Clin Res Cardiol: 30 Oct 2019; 108:1297-1308 | PMID: 30980206
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Abstract

A novel risk score to predict survival in advanced heart failure due to cardiac amyloidosis.

Kreusser MM, Volz MJ, Knop B, Ehlermann P, ... Katus HA, Raake PW
Background
Cardiac amyloidosis, caused by deposition of immunoglobulin light chains (AL) or transthyretin (ATTR), carries a poor prognosis. Established risk scores for amyloidosis may not predict outcomes in those patients who develop advanced heart failure and who are potential candidates for heart transplantation. Here, we aimed to identify predictive parameters for patients with severe heart failure due to amyloidosis.
Methods
Out of > 1000 patients with cardiac amyloidosis (AL or ATTR) admitted to our centre between September 1998 and January 2016, a cohort of 120 patients with a complete cardiac assessment at diagnosis, including right heart catheterization, echocardiography and biomarkers, was analysed retrospectively in this study. Primary endpoint was all-cause mortality. We performed univariate and multivariate Cox regression analysis, generated risk scores to predict outcomes in AL and ATTR amyloidosis and compared those to established risk models for amyloidosis.
Results
In the Cox multivariate model, high-sensitivity troponin T (hsTnT; hazard ratio (HR) 1.003; confidence interval (CI) 1.001-1.005; p = 0.009) and mean pulmonary artery pressure (HR 1.061; CI 1.024-1.100; p = 0.001) were found to significantly and independently predict outcomes for AL amyloidosis, whereas QRS duration (HR 1.021; CI 1.004-1.039; p = 0.013), hsTnT (HR 1.021; CI 1.006-1.036; p = 0.006) and N-terminal pro-brain natriuretic peptide (HR 1.0003; CI 1.0001-1.0004; p = 0.002) were the best predictors for ATTR amyloidosis. A simple risk score (\"HeiRisk\") including these parameters for AL and ATTR allowed a more precise risk stratification in our patient population compared to established risk models.
Conclusions
Risk stratification for cardiac amyloidosis with the newly developed \"HeiRisk\" score may be superior to other staging systems for patients with advanced heart failure due to amyloid cardiomyopathy.



Clin Res Cardiol: 18 Oct 2019; epub ahead of print
Kreusser MM, Volz MJ, Knop B, Ehlermann P, ... Katus HA, Raake PW
Clin Res Cardiol: 18 Oct 2019; epub ahead of print | PMID: 31630214
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Abstract

Angiotensin-converting-enzyme inhibitors in hemodynamic congestion: a meta-analysis of early studies.

Jobs A, Abdin A, de Waha-Thiele S, Eitel I, ... de Wit C, Vonthein R
Aim
Major clinical trials have shown that angiotensin-converting enzyme (ACE) inhibitors reduce mortality and morbidity in congestive heart failure (HF). Prior to these seminal findings hemodynamic effects of ACE inhibitors were examined in small studies. We aimed to review these studies systematically and meta-analyze the effects of ACE inhibitors on hemodynamics in HF.
Methods and results
We identified studies investigating the acute hemodynamic effect of ACE inhibitors in naïve patients with congestive heart failure by searching PubMed and the Cochrane Central Register of Controlled Trials. We extracted the changes in hemodynamic measures and their standard errors from study reports or calculated these values from baseline and post-medication measurements. Data were pooled using random effects models. In total, 41 studies with 46 independent cohorts consisting of 676 patients were included. ACE inhibitor treatment reduced pulmonary capillary wedge pressure by 7.3 (95% confidence interval 6.4-8.2) mmHg and right atrial pressure by 3.7 (95% confidence interval 1.3-6.1) mmHg in patients with HF. Cardiac index increased by 0.4 (95% confidence interval 0.2-0.6) ml/min/m. Changes in hemodynamic measures were strongly connected to each other in weighted simple linear regression models.
Conclusion
Angiotensin-converting enzyme-inhibitors acutely reduced cardiac filling pressures and increased cardiac output in patients with congestive heart failure who were naïve for these drugs. These data indicate that ACE inhibitors exhibit a strong decongesting effect in congestive heart failure. In light of their impact on long-term prognosis, ACE inhibitors should also be considered as decongesting drugs in stable patients.



Clin Res Cardiol: 30 Oct 2019; 108:1240-1248
Jobs A, Abdin A, de Waha-Thiele S, Eitel I, ... de Wit C, Vonthein R
Clin Res Cardiol: 30 Oct 2019; 108:1240-1248 | PMID: 30895374
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Abstract

Mean BMI, visit-to-visit BMI variability and BMI changes during follow-up in patients with acute myocardial infarction with systolic dysfunction and/or heart failure: insights from the High-Risk Myocardial Infarction Initiative.

Stienen S, Ferreira JP, Girerd N, Duarte K, ... Rossignol P,
Background
In patients with acute myocardial infarction (MI), BMI < 18.5 kg/m and a decrease in BMI during follow-up have been associated with poor prognosis. For BMI ≥ 25 kg/m, an \"obesity paradox\" has been suggested. Recently, high visit-to-visit BMI variability has also been associated with poor prognosis in patients with coronary artery disease.
Aims
To simultaneously evaluate several BMI measurements and study their association with cardiovascular (CV) outcomes in a large cohort of patients with acute myocardial infarction (MI) and left ventricular (LV) systolic dysfunction, heart failure (HF) or both.
Methods
The high-risk MI dataset is pooled from four trials: CAPRICORN, EPHESUS, OPTIMAAL and VALIANT. Mean BMI, change from baseline, and variability were assessed during follow-up. The primary outcome was CV death. Cox-proportional hazard models were performed to study the association between the various BMI parameters and outcomes (median follow-up = 1.8 years).
Results
A total of 12,719 patients were included (72% male, mean age 65 ± 11 years). Mean, change and visit-to-visit variability in BMI had a non-linear association with CV death (P < 0.001). Mean BMI < 26 kg/m (vs. ≥ 26-35 kg/m) and BMI decrease during follow-up were independently associated with CV death (adjusted HR 1.32, 95% CI 1.16-1.51, P < 0.001 and adjusted HR 1.57, 95% CI 1.40-1.76, P < 0.001, respectively). Low and high BMI variability (< 2% and > 4%) were associated with increased event-rates, but lost statistical significance in sensitivity analysis including patients with ≥ 5 measurements or excluding patients with HF hospitalization, suggesting that BMI variability may be particularly associated with HF hospitalizations.
Conclusion
Mean BMI < 26 kg/m and a BMI decrease during follow-up were independently associated with CV death in patients with MI and LV systolic dysfunction, HF or both. These associations likely reflect poorer patient status and causality cannot be inferred.



Clin Res Cardiol: 30 Oct 2019; 108:1215-1225
Stienen S, Ferreira JP, Girerd N, Duarte K, ... Rossignol P,
Clin Res Cardiol: 30 Oct 2019; 108:1215-1225 | PMID: 30953180
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Abstract

Does rhythm matter in acute heart failure? An insight from the British Society for Heart Failure National Audit.

Anderson SG, Shoaib A, Myint PK, Cleland JG, ... Garratt CJ, Mamas MA
Background
Atrial fibrillation (AF) is the most common sustained arrhythmia in patients with acute heart failure (AHF). The presence of AF is associated with adverse prognosis in patients with chronic heart failure (CHF) but little is known about its impact in AHF.
Methods
Data were collected between April 2007 and March 2013 across 185 (> 95%) hospitals in England and Wales from patients with a primary death or a discharge diagnosis of AHF. We investigated the association between the presence of AF and all-cause mortality during the index hospital admission, at 30 days and 1 year post-discharge.
Results
Of 96,593 patients admitted with AHF, 44,642 (46%) were in sinus rhythm (SR) and 51,951 (54%) in AF. Patients with AF were older (mean age 79.8 (79.7-80) versus 74.7 (74.5-74.7) years; p < 0.001), than those in SR. In a multivariable analysis, AF was independently associated with mortality at all time points, in hospital (HR 1.15, 95% CI 1.09-1.21, p < 0.0001), 30 days (HR 1.13, 95% CI 1.08-1.19, p < 0.0001), and 1 year (HR 1.09, 95% CI 1.05-1.12, p < 0.0001). In subgroup analyses, AF was independently associated with worse 30-day outcome irrespective of sex, ventricular phenotype and in all age groups except in those aged between 55 and 74 years.
Conclusion
AF is independently associated with adverse prognosis in AHF during admission and up to 1 year post-discharge. As the clinical burden of concomitant AF and AHF increases, further refinement in the detection, treatment and prevention of AF-related complications may have a role in improving patient outcomes.



Clin Res Cardiol: 30 Oct 2019; 108:1276-1286
Anderson SG, Shoaib A, Myint PK, Cleland JG, ... Garratt CJ, Mamas MA
Clin Res Cardiol: 30 Oct 2019; 108:1276-1286 | PMID: 30963233
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Abstract

Outcome differences and device performance of the subcutaneous ICD in patients with and without structural heart disease.

Willy K, Reinke F, Bögeholz N, Ellermann C, ... Eckardt L, Frommeyer G
Background
The performance of the subcutaneous ICD (S-ICDâ„¢) has been described in different kinds of heart disease and has been proven to be an important advance in prevention of sudden cardiac death (SCD). While positive experiences with the S-ICDâ„¢ initially came from collectives of patients without structural heart diseases, positive results have also been collected from cohorts with structural heart disease.
Materials and methods
All S-ICD™ patients with either ischemic cardiomyopathy (ICM), dilated cardiomyopathy (DCM) or hypertrophic cardiomyopathy (HCM) as the main indication for ICD implantation (n = 144 patients) or electrical heart disease/idiopathic ventricular fibrillation (n = 83 patients) in our large-scaled single-center S-ICD™ registry were included in this study. Baseline characteristics, appropriate and inappropriate shocks, and complications were documented in a mean follow-up of 18 ± 15 months.
Results
Baseline characteristics were significantly different between the two groups in most categories. In contrast, there was no difference concerning neither appropriate nor inappropriate shock delivery between the two groups. Also other outcome parameters such as need for surgical revisions and all-cause mortality did not differ. There was a significant difference between the first- and second-generation S-ICDsâ„¢ in inadequate shocks mainly driven by patients with HCM.
Conclusion
In our study, S-ICDâ„¢ performance was similar in patients with and without structural heart disease. Decision pro- or contra-S-ICDâ„¢ should be made rather on the basis of expected shock rate and probability of the need for future anti-tachycardia or anti-bradycardia pacing than in dependence of the underlying heart disease.



Clin Res Cardiol: 30 Oct 2019; epub ahead of print
Willy K, Reinke F, Bögeholz N, Ellermann C, ... Eckardt L, Frommeyer G
Clin Res Cardiol: 30 Oct 2019; epub ahead of print | PMID: 31667624
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Abstract

Coronary microvascular dysfunction in patients with acute coronary syndrome and no obstructive coronary artery disease.

De Vita A, Manfredonia L, Lamendola P, Villano A, ... Lanza GA, Crea F
Background
Between 10 and 15% of patients admitted for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) show no obstructive coronary artery disease (NO-CAD) at angiography. Coronary microvascular spasm is a possible mechanism of the syndrome, but there are scarce data about coronary microvascular function in these patients.
Objectives
To assess coronary microvascular function in patients with NSTE-ACS and NO-CAD.
Methods
We studied 30 patients (67 ± 10 years, 19 female) with NSTE-ACS and NO-CAD. Specific causes of NSTE-ACS presentation (e.g., variant angina, takotsubo disease, tachyarrhythmias, etc.) were excluded. Coronary blood flow (CBF) velocity response to IV ergonovine (6 µg/kg up to a maximal dose of 400 µg) was evaluated before discharge by transthoracic Doppler echocardiography. CBF response to IV adenosine (140 μg/kg/min) and cold pressor test (CPT) was also assessed after 1 month. Ten age- and sex-matched patients with non-cardiac chest pain served as controls. Vasoactive tests were repeated after 12 months in 10 NSTE-ACS patients.
Results
The ergonovine/basal CBF velocity ratio was 0.79 ± 0.09 and 0.99 ± 0.01 in patients and controls, respectively (p < 0.001). The adenosine/basal CBF velocity ratio was 1.46 ± 0.2 and 3.25 ± 1.2 in patients and controls, respectively (p < 0.001), and the CPT/basal CBF velocity ratio was 1.36 ± 0.2 and 2.43 ± 0.3 in the 2 groups, respectively (p < 0.001). In 10 patients assessed after 12 months, CBF velocity responses to ergonovine, adenosine, and CPT were found to be unchanged.
Conclusions
Patients with NSTE-ACS and NO-CAD exhibit a significant coronary dysfunction, which seems to involve both an increased constrictor reactivity, likely mainly involving coronary microcirculation, and a reduced microvascular dilator function, both persisting at 12-month follow-up.



Clin Res Cardiol: 29 Nov 2019; 108:1364-1370
De Vita A, Manfredonia L, Lamendola P, Villano A, ... Lanza GA, Crea F
Clin Res Cardiol: 29 Nov 2019; 108:1364-1370 | PMID: 30927055
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Abstract

Percutaneous left atrial appendage closure using the TrueFusionâ„¢ fusion-imaging technology.

Nelles D, Schrickel JW, Nickenig G, Sedaghat A
Objective
To describe percutaneous left atrial appendage closure (LAAc) in a patient with recurrent gastric ulcer bleeding with the help of the TrueFusionâ„¢ fusion-imaging system.
Method and results
In a patient with paroxysmal atrial fibrillation, the need for an effective oral anticoagulation and recurrent gastrointestinal bleeding, left atrial appendage closure (LAAc) was performed under guidance of the TrueFusion™ fusion-imaging technology (Siemens Healthineers, Erlangen, Germany) to enhance procedural precision, save radiation time and contrast dye. Left atrial appendage closure was performed with the use of a 20 mm Amplatzer Amulet™ (Abbott Laboratories, Chicago, IL, USA) using the TrueFusion™ system under mild sedation with minimal use of contrast. Intraprocedural transesophageal echocardiography revealed complete LAA occlusion without residual flow. The patient was uneventfully discharged on the second postoperative day.
Conclusion
LAAc using an integrated approach combining ultrasound and live fluoroscopy, as provided by the TrueFusionâ„¢, is safe and feasible. Target-oriented device navigation and synchronized image orientation as provided by fusion imaging may potentially be beneficial regarding radiation time, contrast dye and periprocedural risk of suboptimal device positioning.



Clin Res Cardiol: 03 Nov 2019; epub ahead of print
Nelles D, Schrickel JW, Nickenig G, Sedaghat A
Clin Res Cardiol: 03 Nov 2019; epub ahead of print | PMID: 31686210
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Abstract

Implementation of an intensified outpatient follow-up protocol improves outcomes in patients with ventricular assist devices.

Hamed S, Schmack B, Mueller F, Ehlermann P, ... Raake PW, Kreusser MM
Background
Ventricular assist devices (VAD) are increasingly used as long-term treatment for advanced heart failure. However, survival after VAD implantation is still unsatisfactory, and no specific outpatient follow-up algorithms have been formally established. Here, we evaluate the effect of an intensified follow-up protocol (IFUP) on survival rates and VAD-associated complications.
Methods and results
This is a retrospective study of 57 patients who received a VAD at our center between February 2013 and December 2017. Inclusion criteria were discharge home after VAD implantation and follow-up in our VAD outpatient clinic. Patients implanted after October 2015 (n = 30) were monitored according to IFUP. This protocol embodied formalized, multi-disciplinary clinical visits every 4-8 weeks including a cardiologist, a cardiothoracic surgeon and a VAD-coordinator and was characterized by optimized anticoagulation and wound management as well as guideline-directed medical therapy. One-year survival in the IFUP patients was 97%, compared to 74% in the pre-IFUP era (p = 0.01). Implementation of IFUP was associated with a 90% risk-reduction for 1-year mortality (relative risk 0.099; p = 0.048). The rate of complications, e.g., device thrombosis and major bleeding, was significantly reduced, resulting in superior event-free survival in the IFUP group (p = 0.003). Furthermore, by implementation of IFUP, a more stable anticoagulation adjustment was achieved as well as an improved adherence to guideline-directed medical therapy.
Conclusion
Implementation of an IFUP for VAD patients is associated with a significant decrease in 1-year all-cause mortality. This emphasizes the need for more vigilance in the management of VAD patients by a dedicated multi-disciplinary team.



Clin Res Cardiol: 30 Oct 2019; 108:1197-1207
Hamed S, Schmack B, Mueller F, Ehlermann P, ... Raake PW, Kreusser MM
Clin Res Cardiol: 30 Oct 2019; 108:1197-1207 | PMID: 30879094
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Abstract

Significance of psychosocial factors in cardiology: update 2018 : Position paper of the German Cardiac Society.

Albus C, Waller C, Fritzsche K, Gunold H, ... Weber CS, Herrmann-Lingen C
Background
Psychosocial factors in cardiovascular diseases are increasingly acknowledged by patients, health care providers and payer organizations. Due to the rapidly increasing body of evidence, the German Cardiac Society has commissioned an update of its 2013 position paper on this topic. The German version was published in 2018 and the current manuscript is an extended translation of the original version.
Methods
This position paper provides a synopsis of the state of knowledge regarding psychosocial factors in the most relevant cardiovascular diseases and gives recommendations with respect to their consideration in clinical practice.
Results
Psychosocial factors such as low socioeconomic status, acute and chronic stress, depression, anxiety and low social support are associated with an unfavorable prognosis. Psychosocial problems and mental comorbidities should be assessed routinely to initiate targeted diagnostics and treatment. For all patients, treatment should consider age and gender differences as well as individual patient preferences. Multimodal treatment concepts should comprise education, physical exercise, motivational counseling and relaxation training or stress management. In cases of mental comorbidities, brief psychosocial interventions by primary care providers or cardiologists, regular psychotherapy and/or medications should be offered. While these interventions have positive effects on psychological symptoms, robust evidence for possible effects on cardiac outcomes is still lacking.
Conclusions
For coronary heart disease, chronic heart failure, arterial hypertension, and some arrhythmias, there is robust evidence supporting the relevance of psychosocial factors, pointing to a need for considering them in cardiological care. However, there are still shortcomings in implementing psychosocial treatment, and prognostic effects of psychotherapy and psychotropic drugs remain uncertain. There is a need for enhanced provider education and more treatment trials.



Clin Res Cardiol: 30 Oct 2019; 108:1175-1196
Albus C, Waller C, Fritzsche K, Gunold H, ... Weber CS, Herrmann-Lingen C
Clin Res Cardiol: 30 Oct 2019; 108:1175-1196 | PMID: 31076853
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Abstract

Epicardial fat accumulation is an independent marker of impaired heart rate recovery in obese patients with obstructive sleep apnea.

Monfort A, Inamo J, Fagour C, Banydeen R, ... Rivkine E, Neviere R
Background
Sympathetic nervous system activation plays a pivotal role in obese patients with obstructive sleep apnea (OSA), contributing to increased cardiovascular risk. Epicardial adipose tissue (EAT) activates cardiac autonomic nervous system. Our main study objective was to investigate effects of these autonomic dysfunction factors on post-exercise heart rate recovery (HRR).
Methods
36 patients, referred for clinical assessment of obesity (BMI > 30 kg/m), underwent overnight polysomnography, transthoracic echocardiography and cardiopulmonary exercise testing.
Results
Compared to non-OSA patients, OSA patients were older and displayed reduced body weight-indexed peak VO. Cardiac output at peak exercise was similar among groups. Peak exercise arterio-venous oxygen content difference D[a-v]O was lower in OSA patients. In univariate linear analysis, age, AHI, EAT thickness, peak VO and diabetes were associated with blunted HRR. Multiple linear regression analysis showed that increased EAT thickness, AHI and diabetes were independently associated with lower HRR. For identical AHI value and diabetes status, HRR significantly decreased by 61.7% for every 1 mm increase of EAT volume (p = 0.011). If HRR was treated as a categorical variable, EAT [odds ratio (OR) 1.78 (95% confidence interval [CI] 1.19-2.66); p = 0.005], and type 2 diabetes [OR 8.97 (95% CI 1.16-69.10); p = 0.035] were the only independent predictors of blunted HRR.
Conclusions
Aerobic capacity and peak exercise D[a-v]O are impaired in obese OSA patients, suggesting abnormal peripheral oxygen extraction. EAT thickness is an independent marker of post-exercise HRR, which is a noninvasive marker of autonomic nerve dysfunction accompanying poor cardiovascular prognosis in obese patients.



Clin Res Cardiol: 30 Oct 2019; 108:1226-1233
Monfort A, Inamo J, Fagour C, Banydeen R, ... Rivkine E, Neviere R
Clin Res Cardiol: 30 Oct 2019; 108:1226-1233 | PMID: 30887111
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Abstract

Validation of the modified Microlife blood pressure monitor in patients with paroxysmal atrial fibrillation.

Huppertz N, Lip GYH, Lane DA
Aims
Undiagnosed atrial fibrillation (AF) accounts for 6% of all strokes, therefore early detection and treatment of the arrhythmia are paramount. Previous research has illustrated that the Microlife WatchBPO3 AFIB, an automated blood pressure (BP) monitor with an inbuilt AF algorithm, accurately detects permanent AF. Currently, limited data exist on whether the modified BP monitor is able to detect paroxysmal AF (PAF). Therefore, this study aims to assess the accuracy of the Microlife WatchBPO3 AFIB monitor to detect PAF against a pacemaker reference standard over a 24-h period.
Methods and results
Forty-eight patients with a pacemaker implanted for sick sinus syndrome and previously documented fast AF participated. Sensitivity of the atrial pacemaker lead was set to allow detection of signals of ≥ 0.5 mV. Patients engaged in their normal daily routine whilst wearing the modified BP monitor. The modified BP monitor demonstrated an overall sensitivity of 76.0% and specificity of 80.8% for detecting PAF. This sensitivity and specificity increased to 100% and 83.1%, respectively, for patients that achieved more than 80% successful BP readings. Compared to day-time readings, night-time readings also demonstrated a lower proportion of movement artefact (14.4% vs. 3.4%), and therefore, a higher sensitivity and specificity of 100% and 84.9%, respectively, for detecting PAF.
Conclusion
The Microlife WatchBPO3 AFIB device has an acceptable diagnostic accuracy to detect PAF; however, movement artefact affects the accuracy of the readings. This modified BP monitor may potentially be useful as a screening tool for AF in patients at high risk of developing stroke.



Clin Res Cardiol: 06 Nov 2019; epub ahead of print
Huppertz N, Lip GYH, Lane DA
Clin Res Cardiol: 06 Nov 2019; epub ahead of print | PMID: 31701215
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Abstract

Mechanical circulatory support with Impella versus intra-aortic balloon pump or medical treatment in cardiogenic shock-a critical appraisal of current data.

Wernly B, Seelmaier C, Leistner D, Stähli BE, ... Thiele H, Lauten A
Aims
Patients suffering from cardiogenic shock (CS) have a high mortality and morbidity. The Impella percutaneous left-ventricular assist device (LVAD) decreases LV preload, increases cardiac output, and improves coronary blood flow. We aimed to review and meta-analyze available data comparing Impella versus intra-aortic pump (IABP) counterpulsation or medical treatment in CS due to acute myocardial infarction or post-cardiac arrest.
Methods and results
Study-level data were analyzed. Heterogeneity was assessed using the I statistic. Risk rates were calculated and obtained using a random-effects model (DerSimonian and Laird). Four studies were found suitable for the final analysis, including 588 patients. Primary endpoint was short-term mortality (in-hospital or 30-day mortality). In a meta-analysis of four studies comparing Impella versus control, Impella was not associated with improved short-term mortality (in-hospital or 30-day mortality; RR 0.84; 95% CI 0.57-1.24; p = 0.38; I 55%). Stroke risk was not increased (RR 1.00; 95% CI 0.36-2.81; p = 1.00; I2 0%), but risk for major bleeding (RR 3.11 95% CI 1.50-6.44; p = 0.002; I 0%) and peripheral ischemia complications (RR 2.58; 95% CI 1.24-5.34; p = 0.01; I 0%) were increased in the Impella group.
Conclusion
In patients suffering from severe CS due to AMI, the use of Impella is not associated with improved short-time survival but with higher complications rates compared to IABP and medical treatment. Better patient selection avoiding Impella implantation in futile situations or in possible lower risk CS might be necessary to elucidate possible advantages of Impella in future studies.



Clin Res Cardiol: 30 Oct 2019; 108:1249-1257
Wernly B, Seelmaier C, Leistner D, Stähli BE, ... Thiele H, Lauten A
Clin Res Cardiol: 30 Oct 2019; 108:1249-1257 | PMID: 30900010
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Impact:
Abstract

High density mapping and catheter ablation of atrial tachycardias in adults with congenital heart disease.

Krause U, Müller MJ, Stellmacher C, Backhoff D, Schneider H, Paul T
Aims
We used a new grid-style multi-electrode mapping catheter (Advisor™ HD Grid, Abbott) and investigated its use for high density mapping of atrial tachycardias in adult patients with congenital heart disease.
Patients and methods
All patients with congenital heart disease who had mapping of atrial tachycardias using the new grid-style catheter between March 2018 and April 2019 were included.
Results
A total of 24 adult patients had high density mapping of atrial tachycardias using the grid-style multi-electrode catheter. Mean procedure duration was 207 ± 72 min., mean fluoroscopy time was 7.1 ± 7.9 min. In patients with right atrial substrates, fluoroscopy time was shorter compared to biatrial or left atrial substrates (0.9 ± 2.2 min for right atrial substrates, n = 19 vs. 6.3 ± 8.3 min for left atrial substrates, n = 2 and 7.5 ± 4.3 min for biatrial substrates, n = 3, p = 0.01). A mean number of 14.814 ± 10.140 endocardial points were collected and 2.319 ± 1244 points were finally used to characterize the tachycardia. Procedural success was achieved in 21/24 (88%) subjects and partial success in 2/24 (8%) patients. Recurrence rate was low (12.5%). In one patient, radiofrequency ablation within the cavotricuspid isthmus resulted in occlusion of a branch of the right coronary artery. No complications related to the use of the mapping catheter itself occurred.
Conclusion
High density mapping of AT using the grid-style catheter showed promising results with respect to procedural and midterm outcome and fluoroscopy time. Using the grid-style catheter might offer advantages compared to other multi-electrode catheters used for high density mapping of AT in patients with CHD.



Clin Res Cardiol: 01 Jan 2020; epub ahead of print
Krause U, Müller MJ, Stellmacher C, Backhoff D, Schneider H, Paul T
Clin Res Cardiol: 01 Jan 2020; epub ahead of print | PMID: 31897601
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Impact:
Abstract

One year VARC-2-defined clinical outcomes after transcatheter aortic valve implantation with the SAPIEN 3.

Pellegrini C, Rheude T, Trenkwalder T, Mayr NP, ... Husser O, Hengstenberg C
Aims
To evaluate 1-year outcome after transcatheter aortic valve implantation (TAVI) using the SAPIEN 3 (S3) prosthesis with emphasis on the composite endpoints \"clinical efficacy after 30 days\" and \"time-related valve safety\" proposed by the updated Valve Academic Research Consortium (VARC-2).
Methods and results
Four hundred and two consecutive patients undergoing transfemoral TAVI with the S3 were enrolled. Mean age was 81 ± 6 years, 43% were female and median logistic EuroSCORE I was 12% [8-19]. Device success was achieved in 93% (374/402) with moderate or severe paravalvular leakage (PVL) in 2%. At 1 year all-cause mortality was 8.9% [95% CI 6.4-12.2] and new permanent pacemaker implantation rate was 16% [95% CI 12.7-20.4]. The composite endpoint time-related valve safety occurred in 29% with structural valve deterioration, defined as elevated gradients or more than moderate PVL, occurring in 13%. The clinical efficacy endpoint after 30 days was observed in 37% of patients with the main contributor symptom worsening with New York Heart Association functional class III + in 17% of cases.
Conclusions
For the first time, VARC-2-defined composite endpoints at 1 year are reported and reveal a considerable proportion of patients experiencing the endpoint of time-related valve safety (29%) and clinical efficacy after 30 days (37%).



Clin Res Cardiol: 30 Oct 2019; 108:1258-1265
Pellegrini C, Rheude T, Trenkwalder T, Mayr NP, ... Husser O, Hengstenberg C
Clin Res Cardiol: 30 Oct 2019; 108:1258-1265 | PMID: 31049679
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Impact:
Abstract

Atrial fibrillation ablation in adults with congenital heart disease on uninterrupted oral anticoagulation is safe and efficient.

Kottmaier M, Baur A, Lund S, Bourier F, ... Deisenhofer I, Hessling G
Background
The prevalence of atrial fibrillation (AF) is significantly higher in adults with congenital heart disease (ACHD) compared to patients without congenital heart disease (CHD). As AF in ACHD patients might have significant hemodynamic consequences, rhythm control is particularly desirable but rarely achieved by antiarrhythmic drugs. The aim of this study was to investigate safety and long-term outcome of AF ablation in ACHD patients.
Methods
All ACHD patients (n = 46) that underwent AF ablation at our centre from 2013 to 2017 were included in the study. CHD was classified as simple (46%), moderate (41%) or complex (13%). The majority of patients (61%) suffered from persistent AF (paroxysmal AF 39%). Persistent AF was present in 57% of patients with simple, in 58% of patients with moderate and 83% of patients with complex CHD. All patients underwent radiofrequency (RF) ablation on uninterrupted oral anticoagulation. Pulmonary vein isolation (PVI) was performed in patients with paroxysmal AF, whereas patients with persistent AF underwent PVI and ablation of complex fractionated atrial electrograms (CFAE).
Results
No major complications occurred. Single-procedure success after 18 months off antiarrhythmic drugs was 61% for paroxysmal AF and 29% for persistent AF (p = 0.003). Multiple procedures (mean 2.1 ± 1.4) increased long-term success to 82% for paroxysmal AF and 48% for persistent AF (p = 0.05). Long-term ablation success was 64% for simple, 62% for moderate and 50% for complex CHD patients.
Conclusions
AF ablation in ACHD patients is feasible and safe regardless of CHD complexity. Success rates in patients with paroxysmal AF are high and comparable to patients without CHD. In ACHD patients with persistent AF, success rates of ablation are markedly reduced which might be due to a different and/or more extensive (bi-)atrial substrate. In the cohort of complex ACHD patients with persistent AF as the dominant AF type, long-term success of AF ablation is limited.



Clin Res Cardiol: 31 Dec 2019; epub ahead of print
Kottmaier M, Baur A, Lund S, Bourier F, ... Deisenhofer I, Hessling G
Clin Res Cardiol: 31 Dec 2019; epub ahead of print | PMID: 31894385
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Impact:
Abstract

Procedural success, safety and patients satisfaction after second ablation of atrial fibrillation in the elderly: results from the German Ablation Registry.

Fink T, Metzner A, Willems S, Eckardt L, ... Senges J, Rillig A
Background
Aged patients are underrepresented in clinical trials on catheter ablation of atrial fibrillation (AF). In addition, results of outcomes after repeat ablation in the elderly are lacking. We report the results of first repeat AF ablation procedures of aged patients from a real-world multicenter prospective registry.
Methods
Patients undergoing second AF ablation included in the prospective, multicenter German Ablation Registry were divided in two groups (age > 70 years (group 1) and age ≤ 70 years (group 2)) and analyzed for procedural characteristics and clinical follow-up.
Results
738 patients were analyzed (108 patients in group 1, 630 patients in group 2). Significantly more aged patients had structural heart disease (56 patients (51.9%) vs. 203 patients (32.2%), p < 0.001). The majority of the patients underwent repeat pulmonary vein isolation (101 patients (93.5%) vs. 593 patients (94.1%), p = 0.98). More aged patients underwent ablation of left atrial linear lesions (78.1% vs. 57.3% of all linear lesions, p = 0.027). There was no difference in the occurrence of peri-procedural complications (7 patients (6.5%) vs. 24 patients (3.8%), p = 0.30). Recurrence of atrial arrhythmias was documented in 45/105 (42.9%) and 252/603 (41.8%) patients with available follow-up in groups 1 and 2 after a median of 447 (400; 532) and 473 (411; 544) days (p = 0.84). A comparable amount of patients were asymptomatic or reported symptom improvement after repeat ablation in both groups (80% (80/100) in group 1 and 77% (446/576) in group 2; p = 0.57).
Conclusion
Repeat ablation for AF in elderly patients can be performed with safety and efficacy comparable to younger patients.



Clin Res Cardiol: 29 Nov 2019; 108:1354-1363
Fink T, Metzner A, Willems S, Eckardt L, ... Senges J, Rillig A
Clin Res Cardiol: 29 Nov 2019; 108:1354-1363 | PMID: 30953179
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Impact:
Abstract

Heart rate, mortality, and the relation with clinical and subclinical cardiovascular diseases: results from the Gutenberg Health Study.

Münzel T, Hahad O, Gori T, Hollmann S, ... Keaney JF, Wild PS
Background
Higher, but also lower resting heart rate (HR), has been associated with increased cardiovascular events and mortality. Little is known about the interplay between HR, cardiovascular risk factors, concomitant diseases, vascular (endothelial) function, neurohormonal biomarkers, and all-cause mortality in the general population. Thus, we aimed to investigate these relationships in a population-based cohort.
Methods
15,010 individuals (aged 35-74 at enrolment in 2007-2012) from the Gutenberg Health Study were analyzed. Multivariable regression modeling was used to assess the relation between the variables and conditional density plots were generated for cardiovascular risk factors, diseases, and mortality to show their dependence on HR.
Results
There were 714 deaths in the total sample at 7.67 ± 1.68 years of follow-up. The prevalence of diabetes mellitus, arterial hypertension, coronary and peripheral artery disease, chronic heart failure, and previous myocardial infarction exhibited a J-shaped association with HR. Mortality showed a similar relation with a nadir of 64 beats per minute (bpm) in the total sample. Each 10 bpm HR reduction in HR < 64 subjects was independently associated with increased mortality (Hazard Ratio 1.36; 95% confidence interval 1.06-1.75). This increased risk was also present in HR > 64 subjects (Hazard Ratio 1.29; 95% confidence interval 1.19-1.41 per 10 bpm increase in HR). Results found for vascular and neurohormonal biomarkers exhibited a differential picture in subjects with a HR below and above the nadir.
Discussion
These results indicate that in addition to a higher HR, a lower HR is associated with increased mortality.



Clin Res Cardiol: 29 Nov 2019; 108:1313-1323
Münzel T, Hahad O, Gori T, Hollmann S, ... Keaney JF, Wild PS
Clin Res Cardiol: 29 Nov 2019; 108:1313-1323 | PMID: 30953178
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Impact:
Abstract

Body mass index and all-cause mortality in patients with atrial fibrillation: insights from the China atrial fibrillation registry study.

Wang L, Du X, Dong JZ, Liu WN, ... Macle L, Ma CS
Background
Impact of body mass index (BMI) on all-cause mortality in atrial fibrillation (AF) patients remains controversial.
Methods
A total of 10,942 AF patients were prospectively enrolled and categorized into four BMI groups: underweight (BMI < 18.5 kg/m), normal weight (BMI 18.5-24 kg/m), overweight (BMI 24-28 kg/m) and obesity (BMI ≥ 28 kg/m). The primary outcome was all-cause mortality. Different Cox proportional hazards models were performed to evaluate the association between BMI and all-cause mortality.
Results
During a median follow-up of 30 months (IQR 18-48 months), 862 deaths events occurred. Compared to normal BMI, higher BMI was associated with a lower mortality risk (overweight: HR 0.70; 95% CI 0.61-0.81, P < 0.0001 and obesity: HR 0.54; 95% CI 0.44-0.67, P < 0.0001) and lower BMI was associated with a higher mortality risk (HR 2.23, 95% CI 1.67-2.97, P < 0.0001).
Conclusion
A reversed relationship between BMI and all-cause mortality in AF patients was found. Higher risk of mortality was observed in underweight patients compared to patients with a normal BMI, while overweight and obese patients had a lower risk of all-cause mortality.
Clinical trial registration
URL: http://www.chictr.org.cn/showproj.aspx?proj=5831. Unique identifier: ChiCTR-OCH-13003729.



Clin Res Cardiol: 29 Nov 2019; 108:1371-1380
Wang L, Du X, Dong JZ, Liu WN, ... Macle L, Ma CS
Clin Res Cardiol: 29 Nov 2019; 108:1371-1380 | PMID: 30953181
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Impact:
Abstract

Amplified P-wave duration predicts new-onset atrial fibrillation in patients with heart failure with preserved ejection fraction.

Müller-Edenborn B, Minners J, Kocher S, Chen J, ... Arentz T, Jadidi A
Background
Atrial fibrillation (AF) increases morbidity and mortality in heart failure with preserved ejection fraction (HFpEF), yet identification of HFpEF-patients at risk for new-onset AF is challenging. Amplified P-wave duration (APWD) non-invasively detects arrhythmogenic atrial substrate with high accuracy. We hypothesized that APWD may help in the prediction of new-onset AF in HFpEF.
Methods
Patients with suspected HFpEF (n = 99, left ventricular ejection fraction > 50%, no evidence of valvulopathy, coronary artery disease, or non-cardiac dyspnea) underwent exercise testing with concomitant right-heart catheterization. Normal resting pulmonary capillary wedge pressure (PCWP; < 12 mmHg) with an increase during exercise > 25.5 mmHg/W/kg defined early HFpEF. Advanced HFpEF was diagnosed with PCWP > 12 mmHg at rest. Arrhythmogenic atrial substrate (defined as APWD > 150 ms) was investigated on digitized standard 12-lead ECGs and patients were followed for new-onset AF at 6-month intervals.
Results
Forty-seven patients had normal exercise haemodynamics and served as controls. Early and advanced HFpEF was diagnosed in 29 and 23 patients, respectively. Eighty-seven per cent of patients with advanced HFpEF had evidence of arrhythmogenic atrial substrate, (APWD 175 ± 29 ms vs. 132 ± 14 ms in controls, p < 0.0001), which was associated with a tenfold increased risk for new-onset AF during 4.6 years of follow-up (hazard ratio [HR] 9.684, 95% CI 2.61-35.89, p < 0.0001). Early HFpEF was neither related to APWD (p = 0.395), nor to a higher risk for AF (HR 3.44, 95% CI 0.57-20.72, p = 0.178). Importantly, the presence of arrhythmogenic substrate was independent of left atrial indexed volume.
Conclusion
The analysis of amplified P-wave duration (APWD) allows for the prediction of new-onset AF in patients with advanced HFpEF.



Clin Res Cardiol: 20 Dec 2019; epub ahead of print
Müller-Edenborn B, Minners J, Kocher S, Chen J, ... Arentz T, Jadidi A
Clin Res Cardiol: 20 Dec 2019; epub ahead of print | PMID: 31863175
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Impact:
Abstract

Feasibility of entirely subcutaneous ICDâ„¢ systems in patients with coronary artery disease.

Willy K, Bettin M, Reinke F, Bögeholz N, ... Eckardt L, Frommeyer G
Background
The subcutaneous ICD (S-ICDâ„¢) is an important advance in device therapy for the prevention of sudden cardiac death (SCD). Although current guidelines recommend S-ICDâ„¢ use, long-term data are still limited, especially in subgroups. Among several cardiac diseases that prone to SCD, coronary artery disease (CAD) carries several peculiarities that may hamper S-ICDâ„¢ therapy in this cohort. CAD can lead to an ischemic cardiomyopathy (ICM) with a reduced left-ventricular ejection fraction (LVEF) and bundle branch blocks, which can be difficult for ICD sensing and discrimination of arrhythmia. CAD is mainly driven by risk factors such as diabetes mellitus, which put these patients at an elevated risk for infectious complications of cardiac devices. Furthermore, in ICM myocardial scars are frequent and are a potential substrate for ventricular tachycardia, which may be accessible for antitachycardia pacing. At the moment, it remains unclear if there is a value of S-ICDâ„¢ therapy in this subgroup. Therefore, this study analysed patients with CAD.
Materials and methods
All S-ICD™ patients with CAD as the main indication for ICD implantation (n = 45 patients) in our large-scaled single-center S-ICD™ registry (n = 249 patients) were included in this study. Baseline characteristics, appropriate and inappropriate shocks, and complications were documented in a mean follow-up of 22.5 ± 8.3 months.
Results
Primary prevention of SCD was the indication for implantation of an S-ICD™ in 28 patients (62%). Of all 45 patients with an overall mean age of 58.1 ± 11.4 years, 40 were male (88%). The mean LVEF was 37.7 ± 12.6%. Three episodes of ventricular arrhythmia (one monomorphic, one polymorphic, one ventricular fibrillation) were adequately terminated in three patients (7%). In only one patient, oversensing resulting in an inappropriate shock was observed, which could be managed by changing the sensing vector. 15 of the examined 45 patients previously had a transvenous ICD, which was explanted due to system-related infections. In only two patients, S-ICD™ was changed to transvenous ICD because of the need of antibradycardia stimulation. There were no S-ICD™ system-related infections.
Conclusion
The S-ICDâ„¢ seems to be a valuable option for the prevention of SCD in CAD patients. Patients with systemic infections of a transvenous ICD and, therefore, a need for an alternative might benefit from the absence of intracardiac leads as the S-ICDâ„¢ is safe and works flawlessly in these patients. Inadequate shock delivery was very rare, while every episode of ventricular arrhythmia was terminated by the first shock.



Clin Res Cardiol: 30 Oct 2019; 108:1234-1239
Willy K, Bettin M, Reinke F, Bögeholz N, ... Eckardt L, Frommeyer G
Clin Res Cardiol: 30 Oct 2019; 108:1234-1239 | PMID: 30903274
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Impact:
Abstract

Time-updated resting heart rate predicts mortality in patients with COPD.

Omlor AJ, Trudzinski FC, Alqudrah M, Seiler F, ... Bals R,

High resting heart rate (RHR) is associated with higher mortality in the general population and in cardiovascular disease. Less is known about the association of RHR with outcome in chronic obstructive pulmonary disease (COPD). In particular, the time-updated RHR (most recent value before the event) appears informative. This is the first study to investigate the association of time-updated RHR with mortality in COPD. We compared the baseline and time-updated RHR related to survival in 2218 COPD patients of the German COSYCONET cohort (COPD and Systemic Consequences-Comorbidities Network). Patients with a baseline RHR > 72 beats per minute (bmp) had a significantly (p = 0.049) higher all-cause mortality risk (adjusted hazard ratio (HR) of 1.37 (1.00-1.87) compared to baseline RHR ≤ 72 bpm. The time-updated RHR > 72 bpm was markedly superior (HR 1.79, 1.30-2.46, p = 0.001). Both, increased baseline and time-updated RHR, were independently associated with low FEV1, low TLCO, a history of diabetes, and medication with short-acting beta agonists (SABAs). In conclusion, increased time-updated RHR is associated with higher mortality in COPD independent of other predictors and superior to baseline RHR. Increased RHR is linked to lung function, comorbidities and medication. Whether RHR is an effective treatment target in COPD, needs to be proven in controlled trials.



Clin Res Cardiol: 15 Nov 2019; epub ahead of print
Omlor AJ, Trudzinski FC, Alqudrah M, Seiler F, ... Bals R,
Clin Res Cardiol: 15 Nov 2019; epub ahead of print | PMID: 31734762
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Impact:
Abstract

Age-dependent differences in clinical phenotype and prognosis in heart failure with mid-range ejection compared with heart failure with reduced or preserved ejection fraction.

Chen X, Savarese G, Dahlström U, Lund LH, Fu M
Background
HFmrEF has been recently proposed as a distinct HF phenotype. How HFmrEF differs from HFrEF and HFpEF according to age remains poorly defined. We aimed to investigate age-dependent differences in heart failure with mid-range (HFmrEF) vs. preserved (HFpEF) and reduced (HFrEF) ejection fraction.
Methods and results
42,987 patients, 23% with HFpEF, 22% with HFmrEF and 55% with HFrEF, enrolled in the Swedish heart failure registry were studied. HFpEF prevalence strongly increased, whereas that of HFrEF strongly decreased with higher age. All cardiac comorbidities and most non-cardiac comorbidities increased with aging, regardless of the HF phenotype. Notably, HFmrEF resembled HFrEF for ischemic heart disease prevalence in all age groups, whereas regarding hypertension it was more similar to HFpEF in age ≥ 80 years, to HFrEF in age < 65 years and intermediate in age 65-80 years. All-cause mortality risk was higher in HFrEF vs. HFmrEF for all age categories, whereas HFmrEF vs. HFpEF reported similar risk in ≥ 80 years old patients and lower risk in < 65 and 65-80 years old patients. Predictors of mortality were more likely cardiac comorbidities in HFrEF but more likely non-cardiac comorbidities in HFpEF and HFmrEF with < 65 years. Differences among HF phenotypes for comorbidities were less pronounced in the other age categories.
Conclusion
HFmrEF appeared as an intermediate phenotype between HFpEF and HFrEF, but for some characteristics such as ischemic heart disease more similar to HFrEF. With aging, HFmrEF resembled more HFpEF. Prognosis was similar in HFmrEF vs. HFpEF and better than in HFrEF.



Clin Res Cardiol: 29 Nov 2019; 108:1394-1405
Chen X, Savarese G, Dahlström U, Lund LH, Fu M
Clin Res Cardiol: 29 Nov 2019; 108:1394-1405 | PMID: 30980205
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Impact:
Abstract

Right ventricular involvement is an important prognostic factor and risk stratification tool in suspected cardiac sarcoidosis: analysis by cardiac magnetic resonance imaging.

Kagioka Y, Yasuda M, Okune M, Kakehi K, ... Miyazaki S, Iwanaga Y
Background
Late gadolinium enhancement imaging (LGE) of the left ventricle (LV) by cardiac magnetic resonance (CMR) has prognostic value for patients with cardiac sarcoidosis (CS). Right ventricle (RV) dysfunction is also associated with adverse outcomes in patients with heart failure. Therefore, we sought to determine if RV LGE and dysfunction predicted adverse events in patients with suspected CS.
Methods
In 103 consecutive patients with suspected CS who underwent CMR, functional and remodeling indexes of both the LV and RV were measured and the extent and localization of LGE were also analyzed. Major adverse cardiac events (MACE) were defined as cardiovascular mortality, severe ventricular tachyarrhythmia, hospitalization with heart failure, and advanced atrioventricular block.
Results
During a median follow-up of 20.6 months, Kaplan-Meier analysis showed that decreased RV ejection fraction (EF) was associated with MACE (P < 0.001) and receiver operating characteristics curve (ROC) analysis indicated good predictive performance of RV EF for MACE (area under the ROC = 0.834). RV EF operated independently of LV EF or LGE extent for predicting MACE. In addition, the presence of LGE in RV was independently associated with MACE (P = 0.011), and a combined analysis of RV EF and RV LGE showed better risk stratification for MACE (P < 0.001).
Conclusions
Both RV EF and LGE were independently associated with MACE and enhanced risk stratification in patients with suspected CS. CMR may be a useful tool for detecting myocardial function and fibrosis in both the LV and RV.



Clin Res Cardiol: 22 Dec 2019; epub ahead of print
Kagioka Y, Yasuda M, Okune M, Kakehi K, ... Miyazaki S, Iwanaga Y
Clin Res Cardiol: 22 Dec 2019; epub ahead of print | PMID: 31872264
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Impact:
Abstract

Carpal tunnel syndrome and spinal canal stenosis: harbingers of transthyretin amyloid cardiomyopathy?

Aus dem Siepen F, Hein S, Prestel S, Baumgärtner C, ... Katus HA, Kristen AV
Background
Carpal tunnel syndrome (CTS) and spinal canal stenosis can be frequently observed in the medical history of patients with transthyretin amyloidosis (ATTR), both in the hereditary (mt-ATTR) and wild-type (wt-ATTR) form. The aim of this retrospective single-center analysis was to determine the prevalence of these findings, delay to diagnosis of systemic amyloidosis and the prognostic value in a large cohort of patients with wt-ATTR and mt-ATTR amyloidosis.
Methods
Medical records of 253 patients diagnosed with wt-ATTR, 136 patients with mt-ATTR and 77 asymptomatic gene carriers were screened for history of CTS and spinal canal stenosis and laboratory analysis, electrocardiography and echocardiographic results, respectively. Clinical follow-up was performed by phone assessment.
Results
History of CTS was present in 77 patients (56%) with mt-ATTR, in 152 patients (60%) with wt-ATTR and even in 10 of the asymptomatic gene carriers (13%). Latency between carpal tunnel surgery and first diagnosis of systemic amyloidosis was significantly longer in wt-ATTR compared to mt-ATTR (117 ± 179 months vs. 66 ± 73 months; p = 0.02). In total, 36 patients (14%) with wt-ATTR and 7 patients (5%) with mt-ATTR had a history of clinically significant spinal canal stenosis. In the subgroup of mt-ATTR, patients with CTS had thicker IVS (19 ± 5 mm vs. 16 ± 5 mm, p < 0.05), higher LV mass index (225 ± 78 g vs. 193 ± 98 g, p < 0.05), lower Karnofsky index (78 ± 15% vs. 83 ± 17%, p < 0.05), and lower mitral annular plane systolic excursion (MAPSE; 9 ± 4 mm vs. 11 ± 5 mm, p < 0.05) compared to patients without CTS, whereas in wt-ATTR no significant differences could be observed. No significant difference in survival was observed between patients with and without CTS (wt-ATTR: 67 vs. 63 months, p = 0.45; mt-ATTR: 74 vs. 63 months, p = 0.60). A combination of CTS and spinal stenosis was present in 32 wt-ATTR patients (12%) and 3 mt-ATTR patients (2.2%).
Conclusions
The prevalence of CTS is high and the latency between CTS surgery and diagnosis of amyloidosis is long among patients with wt-ATTR and mt-ATTR. CTS might be predictive for future occurrence of systemic (predominantly cardiac) ATTR amyloidosis.



Clin Res Cardiol: 29 Nov 2019; 108:1324-1330
Aus dem Siepen F, Hein S, Prestel S, Baumgärtner C, ... Katus HA, Kristen AV
Clin Res Cardiol: 29 Nov 2019; 108:1324-1330 | PMID: 30953182
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Impact:
Abstract

Contemporary scientometric analyses using a novel web application: the science performance evaluation (SciPE) approach.

Scholz SS, Dillmann M, Flohr A, Backes C, ... Keller A, Mahfoud F
Aims
We aimed at developing a structured study protocol utilizing the bibliographic web-application science performance evaluation (SciPE) to perform comprehensive scientometric analyses.
Methods and results
Metadata related to publications derived from online databases were processed and visualized by transferring the information to an undirected multipartite graph and distinct partitioned sets of nodes. Also, institution-specific data were normalized and merged allowing precise geocoordinate positioning, to enable heatmapping and valid identification. As a result, verified, processed data regarding articles, institutions, journals, authors gender, nations and subject categories can be obtained. We recommend including the total number of publications, citations, the population, research institutions, gross domestic product, and the country-specific modified Hirsch Index and to form corresponding ratios (e.g., population/publication). Also, our approach includes implementation of bioinformatical methods such as heatmapping based on exact geocoordinates, simple chord diagrams, and the central implementation of specific ratios with plain visualization techniques.
Conclusion
This protocol allows precise conduction of contemporaneous scientometric analyses based on bioinformatic and meta-analytical techniques, allowing to evaluate and contextualize scientific efforts. Data presentation with the depicted visualization techniques is mandatory for transparent and consistent analyses of research output across different nations and topics. Research performance can then be discussed in a synopsis of all findings.



Clin Res Cardiol: 03 Nov 2019; epub ahead of print
Scholz SS, Dillmann M, Flohr A, Backes C, ... Keller A, Mahfoud F
Clin Res Cardiol: 03 Nov 2019; epub ahead of print | PMID: 31686209
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Impact:
Abstract

Left atrial roof ablation in patients with persistent atrial fibrillation using the second-generation cryoballoon: benefit or wasted time?

Kuniss M, Akkaya E, Berkowitsch A, Zaltsberg S, ... Hamm CW, Neumann T
Introduction
It is unknown whether left atrial (LA) roof ablation combined with pulmonary vein isolation (PVI) using a second-generation cryoballoon provides additional benefit beyond that of PVI alone in patients with persistent atrial fibrillation (AF). The aim of this study was to compare arrhythmia recurrence rates after PVI alone versus PVI plus LA roof ablation.
Methods and results
In this observational study, we analyzed 399 symptomatic patients with persistent AF treated with cryoballoon ablation. After univariate and multivariate analyses of the entire cohort, propensity score matching resulted in two groups of 86 patients each: (1) PVI plus LA roof ablation (PVI-plus group) and (2) PVI alone (PVI-only group). The primary endpoint was the first documented > 30-s arrhythmia recurrence after a 3-month blanking period. PVI was successful in all patients. A bidirectional conduction block across the LA roof was verified in 91.9% of patients in the PVI-plus group. During a median mid-term follow-up of 33 months, 21 patients (24.4%) in the PVI-plus group and 37 patients (43.0%) in the PVI-only group (P = 0.01) reached the primary endpoint. Multivariate analysis revealed AF history > 2 years (hazard ratio [HR] = 2.04, P < 0.01), LA area > 21 cm (HR = 2.36, P < 0.01), female sex (HR = 1.92, P = 0.02), and LA roof ablation (HR = 0.47, P < 0.01) as significant predictors of outcome.
Conclusions
We observed a significant difference in arrhythmia recurrence rates between the two groups. LA roof ablation is an effective adjuvant treatment option that shows improved outcome compared with PVI alone.



Clin Res Cardiol: 29 Oct 2019; epub ahead of print
Kuniss M, Akkaya E, Berkowitsch A, Zaltsberg S, ... Hamm CW, Neumann T
Clin Res Cardiol: 29 Oct 2019; epub ahead of print | PMID: 31667623
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Impact:
Abstract

Compared with matched controls, patients with postoperative atrial fibrillation (POAF) have increased long-term AF after CABG, and POAF is further associated with increased ischemic stroke, heart failure and mortality even after adjustment for AF.

Thorén E, Wernroth ML, Christersson C, Grinnemo KH, Jidéus L, Ståhle E
Objective
To analyze (1) associations between postoperative atrial fibrillation (POAF) after CABG and long-term cardiovascular outcome, (2) whether associations were influenced by AF during follow-up, and (3) if morbidities associated with POAF contribute to mortality.
Methods
An observational cohort study of 7145 in-hospital survivors after isolated CABG (1996-2012), with preoperative sinus rhythm and without AF history. Incidence of AF was compared with matched controls. Time-updated covariates were used to adjust for POAF-related morbidities during follow-up, including AF.
Results
Thirty-one percent of patients developed POAF. Median follow-up was 9.8 years. POAF patients had increased AF compared with matched controls (HR 3.03; 95% CI 2.66-3.49), while AF occurrence in non-POAF patients was similar to controls (1.00; 0.89-1.13). The observed AF increase among POAF patients compared with controls persisted over time (> 10 years 2.73; 2.13-3.51). Conversely, the non-POAF cohort showed no AF increase beyond the first postoperative year. Further, POAF was associated with long-term AF (adjusted HR 3.20; 95% CI 2.73-3.76), ischemic stroke (1.23; 1.06-1.42), heart failure (1.44; 1.27-1.63), overall mortality (1.21; 1.11-1.32), cardiac mortality (1.35; 1.18-1.54), and cerebrovascular mortality (1.54; 1.17-2.02). These associations remained after adjustment for AF during follow-up. Adjustment for other POAF-associated morbidities weakened the association between POAF and overall mortality, which became non-significant.
Conclusions
Patients with POAF after CABG had three times the incidence of long-term AF compared with both non-POAF patients and matched controls. POAF was associated with long-term ischemic stroke, heart failure, and corresponding mortality even after adjustment for AF during follow-up. The increased overall mortality was partly explained by morbidities associated with POAF.



Clin Res Cardiol: 07 Feb 2020; epub ahead of print
Thorén E, Wernroth ML, Christersson C, Grinnemo KH, Jidéus L, Ståhle E
Clin Res Cardiol: 07 Feb 2020; epub ahead of print | PMID: 32036429
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Impact:
Abstract

Association of estimated plasma volume status with hemodynamic and echocardiographic parameters.

Kobayashi M, Huttin O, Donal E, Duarte K, ... Rossignol P, Girerd N
Background
Estimated plasma volume status (ePVS) has diagnostic and prognostic value in patients with heart failure (HF). However, it remains unclear which congestion markers (i.e., biological, imaging, and hemodynamic markers) are preferentially associated with ePVS. In addition, there is evidence of sex differences in both the hematopoietic process and myocardial structure/function.
Method and results
Patients with significant dyspnea (NYHA ≥ 2) underwent echocardiography and lung ultrasound within 4 h prior to cardiac catheterization. Patients were divided according to tertiles based on sex-specific ePVS thresholds calculated from hemoglobin and hematocrit measurements using Duarte\'s formula. Among the 78 included patients (median age 74.5 years; males 69.2%; HF 48.7%), median ePVS was 4.1 (percentile = 3.7-4.9) mL/g in males (N = 54) and 4.8 (4.4-5.3) mL/g in females (N = 24). Patients with the highest ePVS had more frequently HF, higher NT-proBNP, larger left atrial volume, and higher E/e\' (all p values < 0.05), but no difference in inferior vena cava diameter or pulmonary congestion assessed by lung ultrasound (all p values > 0.10). In multivariable analysis, higher E/e\' and lower diastolic blood pressure were significantly associated with increased ePVS. The association between ePVS and congestion variables was not sex-dependent except for left-ventricular end-diastolic pressure, which was only correlated with ePVS in females (Spearman Rho = 0.53, p < 0.01 in females and Spearman Rho = - 0.04, p = 0.76 in males; p = 0.08).
Conclusion
ePVS is associated with E/e\' regardless of sex, while only associated with invasively measured left-ventricular end-diastolic pressure in females. These results suggest that ePVS is preferably associated with left-sided hemodynamic markers of congestion.



Clin Res Cardiol: 30 Jan 2020; epub ahead of print
Kobayashi M, Huttin O, Donal E, Duarte K, ... Rossignol P, Girerd N
Clin Res Cardiol: 30 Jan 2020; epub ahead of print | PMID: 32006155
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Impact:
Abstract

Early and late risk of ischemic stroke after TAVR as compared to a nationwide background population.

De Backer O, Butt JH, Wong YH, Torp-Pedersen C, ... Køber L, Søndergaard L

Ischemic stroke is a feared complication associated with transcatheter aortic valve replacement (TAVR). Data on the late risk of ischemic stroke following TAVR are scarce. This study aimed to investigate the early (0-90 days) and late (90 days-5 years) risk of ischemic cerebrovascular events (CVE) in a large, unselected cohort of patients undergoing TAVR and to compare this risk with a matched background population. Therefore, all patients undergoing first-time TAVR in Denmark were matched to a background population (controls) in a 1:4 ratio based on age, sex, atrial fibrillation (AF), and the major stroke risk factors. A total of 2455 TAVR patients were matched with 9820 controls. TAVR was associated with a significantly higher ischemic CVE risk as compared with their controls in the early phase [hazard ratio (HR) 5.35 [95% CI 3.50-8.17]; p < 0.001) but not in the late phase (HR 1.17 [95% CI 0.94-1.46]; p = 0.15). In a predefined stratified analysis, no patient-related factors were associated with this higher CVE risk in the early phase. The cumulative 90-day ischemic CVE risk was the lowest in TAVR-patients with known AF receiving oral anticoagulant (OAC) therapy (1.3% [95% CI 0.6-2.5%] and was two-fold higher in OAC-naïve TAVR-patients (2.4% [95% CI 1.8-3.3%] in patients without AF and 2.5% [95% CI 0.9-5.3%] in patients with AF). In conclusion, TAVR was associated with an increased risk of ischemic CVE in the early phase, but not in the late phase, as compared to their matched controls-OAC therapy reduced this early risk of ischemic CVE by half.



Clin Res Cardiol: 29 Oct 2019; epub ahead of print
De Backer O, Butt JH, Wong YH, Torp-Pedersen C, ... Køber L, Søndergaard L
Clin Res Cardiol: 29 Oct 2019; epub ahead of print | PMID: 31667622
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Impact:
Abstract

Obesity paradox and perioperative myocardial infarction/injury in non-cardiac surgery.

Hidvegi R, Puelacher C, Gualandro DM, Lampart A, ... Mueller C,
Background
The impact of obesity on the incidence of perioperative myocardial infarction/injury (PMI) and mortality following non-cardiac surgery is not well understood.
Methods
We performed a prospective diagnostic study enrolling consecutive patients undergoing non-cardiac surgery, who were considered at increased cardiovascular risk. All patients were screened for PMI, defined as an absolute increase from preoperative to postoperative sensitive/high-sensitivity cardiac troponin T (hs-cTnT) concentrations. The body mass index (BMI) was classified according to the WHO classification (underweight< 18 kg/m, normal weight 18-24.9 kg/m, overweight 25-29.9 kg/m, obesity class I 30-34.9 kg/m, obesity class II 35-39.9 kg/m, obesity class III > 40 kg/m). The incidence of PMI and all-cause mortality at 365 days, both stratified according to BMI.
Results
We enrolled 4277 patients who had undergone 5413 surgeries. The median BMI was 26 kg/m (interquartile range 23-30 kg/m). Incidence of PMI showed a non-linear relationship with BMI and ranged from 12% (95% CI 9-14%) in obesity class I to 19% (95% CI 17-42%) in the underweight group. This was confirmed in multivariable analysis with obesity class I. showing the lowest risk (adjusted OR 0.64; 95% CI 0.49-0.83) for developing PMI. Mortality at 365 days was lower in all obesity groups compared to patients with normal body weight (e.g., unadjusted OR 0.54 (95% CI 0.39-0.73) and adjusted OR 0.52 (95% CI 0.38-0.71) in obesity class I).
Conclusion
Obesity class I was associated with a lower incidence of PMI, and obesity in general was associated with a lower all-cause mortality at 365 days.



Clin Res Cardiol: 04 Feb 2020; epub ahead of print
Hidvegi R, Puelacher C, Gualandro DM, Lampart A, ... Mueller C,
Clin Res Cardiol: 04 Feb 2020; epub ahead of print | PMID: 32025837
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Impact:
Abstract

Effect of baroreflex activation therapy on renal sodium excretion in patients with resistant hypertension.

Lipphardt M, Koziolek MJ, Lehnig LY, Schäfer AK, ... Lüders S, Wallbach M
Objective
Activation of the sympathetic nervous system increases sodium retention in resistant hypertension. Baroreflex activation therapy (BAT) is an interventional method to reduce sympathetic overactivity in patients with resistant hypertension. This study aimed to assess the effect of BAT on urinary sodium excretion.
Methods
From 2012 to 2015, consecutive patients with resistant hypertension and blood pressure (BP) above target despite polypharmacy strategies were consecutively included in this observational study. BAT was provided with the individual adaption of programmed parameters over the first months. 24-h urinary sodium excretion (UNa) was estimated at baseline and after 6 months using the Kawasaki formula in patients undergoing BAT. Additionally, the fractional sodium excretion, plasma renin activity, and aldosterone levels were assessed.
Results
Forty-two patients completed the 6-month follow-up period. Office systolic and ambulatory 24-h systolic BP at baseline were 169 ± 27 mmHg and 148 ± 16 mmHg despite a median intake of 7(3-9) antihypertensive drugs. After 6 months of BAT, systolic office BP decreased to 150 ± 29 mmHg (p < 0.01), 24-h systolic BP to 142 ± 22 mmHg (p = 0.04) and 24-h UNa increased by 37% compared to baseline (128 ± 66 vs. 155 ± 83 mmol/day, p < 0.01). These findings were accompanied by a significant increase in fractional sodium excretion (0.74% [0.43-1.47] to 0.92% [0.61-1.92]; p = 0.02). However, in contrast to the significant BP reduction, eGFR, plasma sodium, renin activity and aldosterone levels did not change during BAT. The increase in sodium excretion was correlated with the change in eGFR (r = 0.371; p = 0.015).
Conclusion
The present study revealed a significant increase of estimated 24-h UNa which may contribute to the long-term BP-lowering effects of this interventional method.



Clin Res Cardiol: 30 Oct 2019; 108:1287-1296
Lipphardt M, Koziolek MJ, Lehnig LY, Schäfer AK, ... Lüders S, Wallbach M
Clin Res Cardiol: 30 Oct 2019; 108:1287-1296 | PMID: 30955077
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Impact:
Abstract

Aortic annulus measurement with computed tomography angiography reduces aortic regurgitation after transfemoral aortic valve replacement compared to 3-D echocardiography: a single-centre experience.

Wystub N, Bäz L, Möbius-Winkler S, Pörner TC, ... Schulze PC, Franz M
Background
Accurate assessment of the aortic annulus is crucial for successful transcatheter aortic valve replacement (TAVR), in particular to prevent paravalvular regurgitation (PVR). We compared aortic annular sizing using multidetector computed tomography (MDCT) and three-dimensional transoesophageal echocardiography (3-D TEE) to determine the predictive value of MDCT.
Methods and results
All patients admitted for transfemoral TAVR [n = 227; 48.9% balloon expandable (Edwards Sapien 3); 51.1% self-expandable (Core Valve, Evolut R)] at our institution from January 2015 until December 2016 were analysed retrospectively. Aortic annular parameters were obtained either by MDCT or 3-D TEE. Additionally, we included a cohort of patients (n = 27) assessed by both MDCT and 3D TEE between October 2017 and April 2018 to enable intra-individual comparison of the two methods. Indications for TAVR were severe degenerative aortic stenosis (AS; 94.7%) or re-stenosis after surgical AVR (5.3%). 74.4% were classified as high-gradient AS. The mean age was 80 (37-94) years and 75.8% presented with NYHA III/IV. STS risk of mortality was intermediate (3.5 ± 2.3). MDCT and 3-D TEE were performed in 116 and 111 patients for aortic annulus sizing, respectively. Significantly larger implants were chosen in the CT group irrespective of prosthesis type or post-dilatation. Follow-up (median at 79 days) revealed significantly less PVR in the MDCT compared to 3-D TEE group (absence of PVR in 59.3% and 40.7%, p = 0.016), without differences in mortality. Patients without PVR or mild PVR had a better clinical performance according to NYHA class (p = 0.016).
Conclusion
MDCT is superior to 3-D TEE in terms of sizing accuracy and clinical outcomes. Reduction of PVR after TAVR with MDCT is likely due to valve annulus undersizing by TEE.



Clin Res Cardiol: 30 Oct 2019; 108:1266-1275
Wystub N, Bäz L, Möbius-Winkler S, Pörner TC, ... Schulze PC, Franz M
Clin Res Cardiol: 30 Oct 2019; 108:1266-1275 | PMID: 30972479
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Abstract

Comparison of current German and European practice in cardiac resynchronization therapy: lessons from the ESC/EHRA/HFA CRT Survey II.

Lawin D, Israel CW, Linde C, Normand C, ... Stellbrink C,
Introduction
The European CRT Survey II was introduced to offer insights into CRT implantation practice in Europe. We compared the national data from the participating German centres with that of the other European countries with regard to differences in patient selection, implant results, and initial properties.
Methods and results
11,088 patients were enrolled in 288 centres from 42 countries between 2015 and 2017. Of these, 675 (6.1%) were included in 17 centres in Germany. Patients from Germany were older, had more comorbidities and more symptoms of heart failure (HF) than patients from other European countries. There were no differences with regard to HF aetiology and guideline-directed medical treatment was overall well implemented. There was a high use of CRT in patients with atrial fibrillation, even higher in German patients. CRT was most often applied due to HF with wide QRS complex (class I recommendation) but with relatively higher frequency in Germany due to HF with primary indication for an implantable cardioverter-defibrillator (class IIb) or a pacemaker with expected pacing dependency (class I). The overall implant success rate was high with some differences in the implant procedure. The use of remote monitoring was lower in Germany.
Conclusion
This analysis from the European CRT Survey II overall shows good guideline adherence, high implantation success and a low rate of complications in daily practice. There are some regional differences in baseline characteristics, CRT indication, and procedural aspects. The use of remote monitoring in Germany lags behind other European countries.



Clin Res Cardiol: 05 Dec 2019; epub ahead of print
Lawin D, Israel CW, Linde C, Normand C, ... Stellbrink C,
Clin Res Cardiol: 05 Dec 2019; epub ahead of print | PMID: 31811440
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Impact:
Abstract

Estimated plasma volume and mortality: analysis from NHANES 1999-2014.

Marawan A, Qayyum R
Background
While estimated plasma volume (ePV) has been studied in some diseases, such as heart failure, the relationship between ePV and all-cause or cause-specific mortality remains unexplored. Therefore, we investigated the association between ePV and all-cause, cardiovascular (CV), and cancer-related mortality among adults in the US.
Method
We used the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2014 and included participants older than 18 years. Mortality data were obtained from the National Death Index and matched to the NHANES participants. ePV was derived using Strauss formula. Cox proportional hazard models were fit to estimate hazard ratios for all-cause and cause-specific mortality without and with adjustment for potential confounders.
Results
Of the 42,705 participants, 5194 died (1121 CV deaths) during mean follow-up of 8.0 (range 0-16.7) years. Mean ± SD age and ePV of the participants were 47.2 ± 19.4 years and 4.2 ± 0.84, respectively. In unadjusted models, 1 unit increase in ePV was associated with 29%, 32%, and 16% increased risk in all-cause (HR 1.29; 95% CI 1.24, 1.35), CV (HR 1.32; 95% CI 1.22, 1.43), and cancer-related (HR 1.16; 95% CI 1.05, 1.27) mortality. Risk remained high in adjusted models (all-cause HR 1.24; 95% CI 1.18, 1.30; CV HR 1.22; 95% CI 1.11, 1.34; cancer-specific HR 1.24; 95% CI 1.10, 1.39). When comparing the highest and lowest ePV quartiles, similar results were noted (adjusted all-cause HR 1.64; 95% CI 1.45, 1.86; CV HR 1.52; 95% CI 1.19, 1.93; cancer HR 1.85; 95% CI 1.38, 2.49).
Conclusion
An increase in ePV was associated with increased all-cause and cause-specific mortality. Further studies are needed to explore the mechanism of this relationship and translation into a better outcome.



Clin Res Cardiol: 04 Feb 2020; epub ahead of print
Marawan A, Qayyum R
Clin Res Cardiol: 04 Feb 2020; epub ahead of print | PMID: 32025836
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Impact:
Abstract

Low serum lathosterol levels associate with fatal cardiovascular disease and excess all-cause mortality: a prospective cohort study.

Weingärtner O, Lütjohann D, Meyer S, Fuhrmann A, ... Sijbrands E, Heine GH
Importance
A more precise identification of patients at \"high cardiovascular risk\" is preeminent in cardiovascular risk stratification.
Objective
To investigate the relationships between markers of cholesterol homeostasis, cardiovascular events and all-cause mortality.
Design, setting and participants
We quantified markers of cholesterol homeostasis by gas chromatography-mass spectrometry in 377 subjects with suspected coronary artery disease, who were not on lipid-lowering drugs at baseline. All patients were followed for occurrence of cardiovascular events and mortality over a period of 4.9 +/- 1.7 years. The standardized mortality ratio (SMR) was calculated as the ratio of the observed and the expected deaths based on the death rates of the Regional Databases Germany, and Poisson regression (rate ratio, RR) was used to compare subgroups. The SMR and RR were standardized for sex, age category and calendar period. In addition, Cox regression (Hazard ratio, HR) was used to determine the effect of co-variables on (cardiovascular) mortality within the cohort.
Main outcomes
Cardiovascular events, cardiovascular mortality and all-cause mortality.
Results
A total of 42 deaths were observed in 1818 person-years corresponding with an SMR of 0.99 (95% CI 0.71-1.33; p = 0.556). A fatal cardiovascular event occurred in 26 patients. Lower levels of lathosterol were associated with increased cardiovascular mortality (HR 1.59; 95% CI: 1.16-2.17; p = 0.004) and excess all-cause mortality (HR 1.41; 95% CI: 1.09-1.85; p = 0.011). Lower lathosterol tertile compared to the adjacent higher tertile was associated with 1.6 times higher all-cause mortality risk (RR 1.60; 95% CI 1.07-2.40; p for trend = 0.022). This corresponded with a 2.3 times higher mortality risk of a lathosterol-LDL ratio equal to or below the median (RR 2.29; 95% CI 1.19-4.43; p = 0.013). None of the other cholesterol homeostasis markers were associated with cardiovascular and all-cause mortality.
Conclusions
In patients not on lipid-lowering agents, low serum lathosterol correlated with increased risk of cardiovascular events and excess all-cause mortality.



Clin Res Cardiol: 29 Nov 2019; 108:1381-1385
Weingärtner O, Lütjohann D, Meyer S, Fuhrmann A, ... Sijbrands E, Heine GH
Clin Res Cardiol: 29 Nov 2019; 108:1381-1385 | PMID: 30949753
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Impact:
Abstract

Higher prevalence of heart failure in rural regions: a population-based study covering 87% of German inhabitants.

Holstiege J, Akmatov MK, Störk S, Steffen A, Bätzing J
Background
So far the extent of regional variation of heart failure (HF) prevalence in Germany is unknown.
Methods
Using a full sample of nationwide claims data covering ambulatory care of approximately 87% of the German population, this study aimed to (i) examine regional differences of HF prevalence on the level of 402 German administrative districts and (ii) investigate factors associated with HF prevalence. This study included all statutory health-insured patients aged ≥ 40 years in 2017, comprising about 40 million individuals. Age- and sex-standardized HF prevalence was estimated on the district level. Two-level logistic regression analysis was employed to study the influence of the district-related factors degree of urbanisation and regional socio-economic status on HF diagnosis, adjusted for the individual\'s age and sex.
Results
HF prevalence in 2017 was 6.0%. Standardized prevalence on the district level varied by a factor of 4.3 (range 2.8-11.9%). Regional socio-economic status and degree of urbanisation were independently associated with HF prevalence. The prevalence increased with decreasing degree of urbanisation. The adjusted risk of suffering from HF was 40% higher in \'rural areas with a low population density\' as compared to \'big urban municipalities\' (odds ratio 1.40, 99% CI 1.24-1.59).
Conclusion
Strong regional variations in HF prevalence may inform future public health policies regarding targeted resource planning and prevention strategies. High prevalence in areas with low population density adds to the challenge of ensuring universal access to health services in rural German regions.



Clin Res Cardiol: 29 Sep 2019; 108:1102-1106
Holstiege J, Akmatov MK, Störk S, Steffen A, Bätzing J
Clin Res Cardiol: 29 Sep 2019; 108:1102-1106 | PMID: 30798347
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Impact:
Abstract

Predictive value of soluble urokinase-type plasminogen activator receptor for mortality in patients with suspected myocardial infarction.

Sörensen NA, Nikorowitsch J, Neumann JT, Rübsamen N, ... Zeller T, Karakas M
Background
Early risk stratification of patients with suspected acute myocardial infarction (AMI) constitutes an unmet need in current daily clinical practice. We aimed to evaluate the predictive value of soluble urokinase-type plasminogen activator receptor (suPAR) levels for 1-year mortality in patients with suspected AMI.
Methods and results
suPAR levels were determined in 1314 patients presenting to the emergency department with suspected AMI. Patients were followed up for 12 months to assess all-cause mortality. Of 1314 patients included, 308 were diagnosed with AMI. Median suPAR levels did not differ between subjects with AMI compared to non-AMI (3.5 ng/ml vs. 3.2 ng/ml, p = 0.066). suPAR levels reliably predicted all-cause mortality after 1 year. Hazard ratio for 1-year mortality was 12.6 (p < 0.001) in the quartile with the highest suPAR levels compared to the first quartile. The prognostic value for 6-month mortality was comparable to an established risk prediction model, the Global Registry of Acute Coronary Events (GRACE) score, with an AUC of 0.79 (95% CI 0.72-0.86) for the GRACE score and 0.77 (95% CI 0.69-0.84) for suPAR. Addition of suPAR improved the GRACE score, as shown by integrated discrimination improvement statistics of 0.036 (p = 0.03) suggesting a further discrimination of events from non-events by the addition of suPAR.
Conclusions
suPAR levels reliably predicted mortality in patients with suspected AMI.
Study registration
http://www.clinicaltrials.gov (NCT02355457).



Clin Res Cardiol: 29 Nov 2019; 108:1386-1393
Sörensen NA, Nikorowitsch J, Neumann JT, Rübsamen N, ... Zeller T, Karakas M
Clin Res Cardiol: 29 Nov 2019; 108:1386-1393 | PMID: 30989318
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Impact:
Abstract

ARNIs: balancing \"the good and the bad\" of neuroendocrine response to HF.

Ferrari R, Cardoso J, Fonseca MC, Aguiar C, ... Rapezzi C,
Background
A new class of drugs-angiotensin receptor, neprylisin inhibitors, ARNI-has shown to be prognostic superior in HFrEF to the sole inhibition of the renin-angiotensin axes with enalapril. The ultimate mechanism of action of ARNIs is unknown.
Aim
We have considered that ARNI exerts a positive modulation of the neuroendocrine balance, with enhancement of the physiological diuresis and dilatation due to neprylisin inhibition by sacubitril. This represents a shift in HF medical therapy always directed to counteract (with inhibitors of the renin-angiotensin system, beta blockers or inhibitors of aldosterone) the so-called \"bad\" neuroendocrine response. Development of ARNI, on the contrary, has led to consider the neuroendocrine response to HFrEF from a different angle, which is to say that the activation is not always deleterious, but it could also be beneficial. This concept is highlighted by the enhancement of the activity of atrial natriuretic peptide, induced by sacubitril/valsartan in the PARADIGM trial, and found as proof from early studies on untreated patients with constrictive pericarditis. The possibility that sacubitril inhibition of neprylisin acts by enhancing substance P and gene-related calcitonin peptide is also considered, as well as the negative effect of neprylisin inhibition.
Conclusions
The beneficial effects of ARNI are related, in part at least, to a positive modulation of the neuroendocrine response to the disease, resulting in an increase of physiological diuresis and dilatation.



Clin Res Cardiol: 16 Sep 2019; epub ahead of print
Ferrari R, Cardoso J, Fonseca MC, Aguiar C, ... Rapezzi C,
Clin Res Cardiol: 16 Sep 2019; epub ahead of print | PMID: 31531687
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Impact:
Abstract

Soluble neprilysin, NT-proBNP, and growth differentiation factor-15 as biomarkers for heart failure in dialysis patients (SONGBIRD).

Claus R, Berliner D, Bavendiek U, Vodovar N, ... Hiss M, Balzer MS
Background
Dialysis patients are at increased risk of HF. However, diagnostic utility of NT-proBNP as a biomarker is decreased in patients on dialysis. GDF-15 and cNEP are biomarkers of distinct mechanisms that may contribute to HF pathophysiology in such cohorts. The aim of this study was to determine whether growth differentiation factor-15 (GDF-15) and circulating neprilysin (cNEP) improve the diagnosis of congestive heart failure (HF) in patients on dialysis.
Methods and results
We compared circulating concentrations of NT-proBNP, GDF-15, and cNEP along with cNEP activity in patients on chronic dialysis without (n = 80) and with HF (n = 73), as diagnosed by clinical parameters and post-dialysis echocardiography. We used correlation, linear and logistic regression as well as receiver operating characteristic (ROC) analyses. Compared to controls, patients with HF had higher median values of NT-proBNP (16,216 [interquartile range, IQR = 27739] vs. 2883 [5866] pg/mL, p < 0.001), GDF-15 (7512 [7084] vs. 6005 [4892] pg/mL, p = 0.014), but not cNEP (315 [107] vs. 318 [124] pg/mL, p = 0.818). Median cNEP activity was significantly lower in HF vs. controls (0.189 [0.223] vs. 0.257 [0.166] nmol/mL/min, p < 0.001). In ROC analyses, a multi-marker model combining clinical covariates, NT-proBNP, GDF-15, and cNEP activity demonstrated best discrimination of HF from controls (AUC = 0.902, 95% CI 0.857-0.947, p < 0.001 vs. base model AUC = 0.785).
Conclusion
We present novel comparative data on physiologically distinct circulating biomarkers for HF in patients on dialysis. cNEP activity but not concentration and GDF-15 provided incremental diagnostic information over clinical covariates and NT-proBNP and may aid in diagnosing HF in dialysis patients.



Clin Res Cardiol: 29 Jan 2020; epub ahead of print
Claus R, Berliner D, Bavendiek U, Vodovar N, ... Hiss M, Balzer MS
Clin Res Cardiol: 29 Jan 2020; epub ahead of print | PMID: 32002632
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Impact:
Abstract

Correlation of machine learning computed tomography-based fractional flow reserve with instantaneous wave free ratio to detect hemodynamically significant coronary stenosis.

Baumann S, Hirt M, Schoepf UJ, Rutsch M, ... Overhoff D, Lossnitzer D
Background
Fractional flow reserve based on coronary CT angiography (CT-FFR) is gaining importance for non-invasive hemodynamic assessment of coronary artery disease (CAD). We evaluated the on-site CT-FFR with a machine learning algorithm (CT-FFR) for the detection of hemodynamically significant coronary artery stenosis in comparison to the invasive reference standard of instantaneous wave free ratio (iFR).
Methods
This study evaluated patients with CAD who had a clinically indicated coronary computed tomography angiography (cCTA) and underwent invasive coronary angiography (ICA) with iFR-measurements. Standard cCTA studies were acquired with third-generation dual-source computed tomography and analyzed with on-site prototype CT-FFR software.
Results
We enrolled 40 patients (73% males, mean age 67 ± 12 years) who had iFR-measurement and CT-FFR calculation. The mean calculation time of CT-FFR values was 11 ± 2 min. The CT-FFR algorithm showed, on per-patient and per-lesion level, respectively, a sensitivity of 92% (95% CI 64-99%) and 87% (95% CI 59-98%), a specificity of 96% (95% CI 81-99%) and 95% (95% CI 84-99%), a positive predictive value of 92% (95% CI 64-99%), and 87% (95% CI 59-98%), and a negative predictive value of 96% (95% CI 81-99%) and 95% (95% CI 84-99%). The area under the receiver operating characteristic curve for CT-FFR on per-lesion level was 0.97 (95% CI 0.91-1.00). Per lesion, the Pearson\'s correlation between the CT-FFR and iFR showed a strong correlation of r = 0.82 (p < 0.0001; 95% CI 0.715-0.920).
Conclusion
On-site CT-FFR correlated well with the invasive reference standard of iFR and allowed for the non-invasive detection of hemodynamically significant coronary stenosis.



Clin Res Cardiol: 28 Oct 2019; epub ahead of print
Baumann S, Hirt M, Schoepf UJ, Rutsch M, ... Overhoff D, Lossnitzer D
Clin Res Cardiol: 28 Oct 2019; epub ahead of print | PMID: 31664509
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Impact:
Abstract

Geographical differences in heart failure characteristics and treatment across Europe: results from the BIOSTAT-CHF study.

Lombardi CM, Ferreira JP, Carubelli V, Anker SD, ... Voors A, Metra M
Background
Geographical differences may impact the treatment of heart failure (HF) and the results of clinical trials. We have investigated the differences between geographical areas across Europe in the BIOSTAT-CHF program.
Methods
Patients with worsening HF enrolled in BIOSTAT-CHF were subdivided, according to the European geographical areas, into those from Northern countries (The Netherlands, Norway, Sweden, UK), Central countries (Germany, Poland, Serbia, Slovenia), and Mediterranean countries (France, Greece, Italy). Patients were compared for baseline characteristics, treatment, and outcomes. The primary endpoint was a composite of all-cause mortality or HF hospitalization.
Results
Among 2516 patients enrolled in BIOSTAT-CHF, 814 (32.3%) were from Northern European centers, 816 (32.4%) from Central European centers, and 886 (35.2%) from Mediterranean centers. Patients from Northern European centers were older, had more severe signs and symptoms of HF, and with lower incidence of non-cardiac comorbidities such as chronic kidney dysfunction, diabetes and, hypertension, compared to those from the Central and Mediterranean centers. Patients receiving ≥ 50% of the target dose of both ACE-I/ARB after the up-titration phase were higher in the Northern European centers compared with the other regions (60% versus 58.7% in the Central European centers and 46.5% in the Mediterranean ones; p < 0.001). The primary endpoint occurred at a higher rate in the Northern centers (44.3% versus 37.4% in central centers and 39.6% in Mediterranean centers; p = 0.014), this difference became non-significant after the adjustment for important confounders. Importantly, treatment up-titration reduced the event rates regardless of the geographical region (p for interaction > 0.05).
Conclusion
The BIOSTAT-CHF study showed significant differences in the clinical features, treatment and prognosis in European patients with HF. Patients from the Mediterranean centers less often had the HF treatments up-titrated; however, the treatment up-titration benefited patients irrespective of their geographical region and should be part of the \"default\" clinical practice.



Clin Res Cardiol: 28 Jan 2020; epub ahead of print
Lombardi CM, Ferreira JP, Carubelli V, Anker SD, ... Voors A, Metra M
Clin Res Cardiol: 28 Jan 2020; epub ahead of print | PMID: 31996990
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Impact:
Abstract

Biventricular myocardial strain analysis using cardiac magnetic resonance feature tracking (CMR-FT) in patients with distinct types of right ventricular diseases comparing arrhythmogenic right ventricular cardiomyopathy (ARVC), right ventricular outflow-tract tachycardia (RVOT-VT), and Brugada syndrome (BrS).

Heermann P, Fritsch H, Koopmann M, Sporns P, ... Schulze-Bahr E, Schülke C
Objectives
As underlying heart diseases of right ventricular tachyarrhythmias, ARVC causes wall-motion abnormalities based on fibrofatty myocardial degeneration, while RVOT-VT and BrS are thought to lack phenotypic MR characteristics. To examine whether cardiac magnetic resonance (CMR) feature tracking (FT) in addition to ARVC objectively facilitates detection of myocardial functional impairments in RVOT-VT and BrS.
Methods
Cine MR datasets of four retrospectively enrolled, age-matched study groups [n = 65; 16 ARVC, 26 RVOT-VT, 9 BrS, 14 healthy volunteers (HV)] were independently assessed by two distinctly experienced investigators regarding myocardial function using CMR-FT. Global strain (%) and strainrate (s) in radial and longitudinal orientation were assessed at RVOT as well as for left (LV) and right (RV) ventricle at a basal, medial and apical section with the addition of a biventricular circumferential orientation.
Results
RV longitudinal and radial basal strain (%) in ARVC (- 12.9 ± 4.2; 11.4 ± 5.1) were significantly impaired compared to RVOT-VT (- 18.0 ± 2.5, p ≤ 0.005; 16.4 ± 5.2, p ≤ 0.05). Synergistically, RVOT endocardial radial strain (%) in ARVC (33.8 ± 22.7) was significantly lower (p ≤ 0.05) than in RVOT-VT (54.3 ± 14.5). For differentiation against BrS, RV basal and medial radial strain values (%) (13.3 ± 6.1; 11.8 ± 2.9) were significantly reduced when compared to HV (21.0 ± 6.9, p ≤ 0.05; 20.1 ± 6.6, p ≤ 0.005), even in case of a normal RV ejection fraction (EF) (> 45%; n = 6) (12.0 ± 2.7 vs. 20.1 ± 6.6, p ≤ 0.05).
Conclusions
CMR-FT facilitates relevant differentiation in patients with right ventricular tachyarrhythmias: between ARVC against RVOT-VT and HV as well as between BrS with even a preserved EF against HV.



Clin Res Cardiol: 29 Sep 2019; 108:1147-1162
Heermann P, Fritsch H, Koopmann M, Sporns P, ... Schulze-Bahr E, Schülke C
Clin Res Cardiol: 29 Sep 2019; 108:1147-1162 | PMID: 30868222
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Abstract

Natriuretic peptides: biomarkers for atrial fibrillation management.

Sepehri Shamloo A, Bollmann A, Dagres N, Hindricks G, Arya A

In clinical practice, atrial fibrillation (AF) is known as the most common sustained arrhythmia. Therefore, identification of individuals at risk of AF development/recurrence or its associated complications has emerged as a hot topic in the field of cardiology. Recently, several biomarkers have been introduced to predict AF and its consequences; however, use of biomarkers in AF management has not been highly recommended by guidelines yet. While utilization of natriuretic peptides (NPs) including brain (B-type) NPs (BNPs) in heart failure management has been well established, their use in relation to AF has not been fully understood. Accordingly, this review article aimed at presenting an overview of the role of NPs in predicting AF development/recurrence as well as its complications and making suggestions for their use in management of patients with AF in clinical settings.



Clin Res Cardiol: 29 Jan 2020; epub ahead of print
Sepehri Shamloo A, Bollmann A, Dagres N, Hindricks G, Arya A
Clin Res Cardiol: 29 Jan 2020; epub ahead of print | PMID: 32002634
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Impact:
Abstract

Implantable cardioverter defibrillators in patients with electrical heart disease and hypertrophic cardiomyopathy: data from the German device registry.

Frommeyer G, Reinke F, Andresen D, Kleemann T, ... Senges J, Eckardt L
Background
Implantable cardioverter- defibrillator (ICD) therapy is established for the prevention of sudden cardiac death (SCD) in different entities. However, data from large patient cohorts with electrical heart disease are rare. Therefore, we investigated these patients as well as patients with hypertrophic cardiomyopathy by analyzing registry data from a multi-center \'real-life\' registry.
Methods
The German Device Registry (DEVICE) is a nationwide, prospective registry with one-year follow-up investigating 5450 patients receiving device implantations in 50 German centers. The present analysis of DEVICE focussed on patients with electrical heart disease or HCM who received an ICD for primary or secondary prevention.
Results
174 patients with HCM and 112 patients with electrical heart disease (long-QT syndrome, Brugada syndrome and arrhythmogenic right ventricular cardiomyopathy) were compared with 5164 other ICD patients. Median follow-up was 17.0 months. Patients in the control group were significantly older. Of note, overall mortality after 1 year was 1.8% in HCM patients, 6.6% in patients with electrical heart disease and 7.3% in the control group. Patients in the control group presented significantly more severe comorbidities. In contrast to HCM patients and the control group where primary prevention was the major indication for ICD implantation, 77.5% of patients with electrical heart disease received an ICD for secondary prevention. The number of surgical revisions was higher in patients with electrical heart disease.
Conclusion
Data from the present registry display a surprisingly high mortality in patients with electrical heart disease equivalent to the control group. A high proportion of patients who received an ICD for secondary prevention may be regarded as a major determinant for these results, while severe comorbidities such as diabetes, hypertension, and renal failure are major determinants for mortality in the control cohort.



Clin Res Cardiol: 30 Jul 2019; epub ahead of print
Frommeyer G, Reinke F, Andresen D, Kleemann T, ... Senges J, Eckardt L
Clin Res Cardiol: 30 Jul 2019; epub ahead of print | PMID: 31367999
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Impact:
Abstract

The potential prognostic utility of salivary galectin-3 concentrations in heart failure.

Zhang X, Karunathilaka N, Senanayake S, Subramaniam VN, ... Atherton JJ, Punyadeera C
Background
Patients with HF are at a higher risk of rehospitalisation and, as such, significant costs to our healthcare system. A non-invasive method to collect body fluids and measure Gal-3 could improve the current management of HF. In this study, we investigated the potential prognostic utility of salivary Galectin-3 (Gal-3) in patients with heart failure (HF).
Methods
We collected saliva samples from patients with HF (n = 105) either at hospital discharge or during routine clinical visits. Gal-3 concentrations in saliva samples were measured by ELISA. The Kaplan-Meier survival curve analysis and Cox proportional regression model were used to determine the potential prognostic utility of salivary Gal-3 concentrations.
Results
The primary end point was either cardiovascular death or hospitalisation. Salivary Gal-3 concentrations were significantly higher (p < 0.05) in patients with HF who subsequently experienced the primary endpoint compared to those who did not. HF patients with salivary Gal-3 concentrations > 172.58 ng/mL had a significantly (p < 0.05) higher cumulative risk of the primary endpoint compared to those with lower salivary Gal-3 concentrations. In patients with HF, salivary Gal-3 concentration was a predictor of the primary endpoint even after adjusting for other covariates.
Conclusions
In our pilot study, HF patients with salivary Gal-3 concentrations of > 172.58 ng/mL demonstrated a higher cumulative risk of the primary outcome compared to those with lower Gal-3 levels, even after adjusting for other variables. Confirming our findings in a larger multi-centre clinical trial in the future would enable salivary Gal-3 measurements to form part of routine management for patients with HF.



Clin Res Cardiol: 08 Oct 2019; epub ahead of print
Zhang X, Karunathilaka N, Senanayake S, Subramaniam VN, ... Atherton JJ, Punyadeera C
Clin Res Cardiol: 08 Oct 2019; epub ahead of print | PMID: 31598750
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Impact:
Abstract

Patient preference for therapies in hypertension: a cross-sectional survey of German patients.

Schmieder RE, Högerl K, Jung S, Bramlage P, Veelken R, Ott C
Background
Hypertension is poorly controlled in numerous patients despite effective medication being available. Catheter-based renal denervation (RDN) has emerged as an alternative treatment option. We aimed to assess how likely patients with elevated blood pressure (BP) are to accept RDN as treatment option.
Methods
A questionnaire-based cross-sectional survey was performed in patients with elevated BP in Germany. Data on patient demographics, clinical characteristics and treatment preferences were collected, anonymized and analyzed.
Results
One thousand and eleven patients completed the survey. Mean age was 66 years (55% male). If not already on medication (n = 172), 38.2% of patients would prefer RDN. Of those already on drug therapy (n = 839), 28.2% would opt for RDN. Patients who were pro-RDN were younger (p < 0.0001) and more often male (p < 0.0001). Nineteen percent would choose RDN if it lowered systolic BP by at least 20 mmHg, more than 40% if they did not have to take any more pills thereafter, and 30% if it would lower BP by at least 10 mmHg. Experiences of side effects and drug adherence were identified as determinants of patient preference. Physicians were the main source of information regarding medical problems (95.5%) and influence patients\' decision regarding therapies (98%).
Conclusions
This survey found that a significant proportion of patients would choose catheter-based RDN over lifelong pharmacotherapy. These patients were younger and more likely to be male but their expectation of the extent of BP decrease with RDN was high. Physicians are key mediators for treatment selection. They need to incorporate patient preferences into shared decision making.



Clin Res Cardiol: 29 Nov 2019; 108:1331-1342
Schmieder RE, Högerl K, Jung S, Bramlage P, Veelken R, Ott C
Clin Res Cardiol: 29 Nov 2019; 108:1331-1342 | PMID: 30941492
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Abstract

Differential effects of inhibition of interleukin 1 and 6 on myocardial, coronary and vascular function.

Ikonomidis I, Pavlidis G, Katsimbri P, Andreadou I, ... Alexopoulos D, Iliodromitis E
Background
Anakinra, an interleukin-1 receptor antagonist and tocilizumab, an interleukin-6 receptor blocker, are used for the treatment of rheumatoid arthritis. We investigated the differential effects of anakinra and tocilizumab on myocardial and vascular function in an atherosclerosis model of patients with rheumatoid arthritis.
Methods
120 patients with rheumatoid arthritis were randomized to anakinra (n = 40), tocilizumab (n = 40) or prednisolone (n = 40) for 3 months. Primary outcome measure was the change of left ventricular longitudinal strain after 3 months of treatment. Additionally, we measured coronary flow reserve, flow-mediated dilatation of the brachial artery, carotid-femoral pulse wave velocity, malondialdehyde and protein carbonyls as oxidative stress markers and C-reactive protein blood levels at baseline and post-treatment.
Results
At baseline, patients among the three treatment arms had similar age, sex, disease activity score and atherosclerotic risk factors. Compared with baseline, all patients had improved longitudinal strain (- 16% vs. - 17.8%), coronary flow reserve (2.56 vs. 2.9), malondialdehyde (2.0 vs. 1.5 µM/L), protein carbonyls (0.0132 vs. 0.0115 nmol/mg), and C-reactive protein post-treatment. In all patients, the percent decrease of malondialdehyde was correlated with percent increase of longitudinal strain (p < 0.001). Compared with tocilizumab and prednisolone, anakinra treatment resulted in a greater improvement of longitudinal strain (18.7% vs. 9.7% vs. 6%) and coronary flow reserve (29% vs. 13% vs. 1%), while pulse wave velocity and brachial blood pressure were improved only after tocilizumab treatment (11 ± 3 vs. 10.3 ± 2 m/s p < 0.05 for all comparisons).
Conclusions
Anakinra is associated with an improvement in cardiac function and tocilizumab with improvement in vascular function.
Clinical trial registration
URL: https:// http://www.clinicaltrials.gov . Unique identifier: NCT03288584.



Clin Res Cardiol: 29 Sep 2019; 108:1093-1101
Ikonomidis I, Pavlidis G, Katsimbri P, Andreadou I, ... Alexopoulos D, Iliodromitis E
Clin Res Cardiol: 29 Sep 2019; 108:1093-1101 | PMID: 30859382
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Impact:
Abstract

Cardioprotective effect of renin-angiotensin inhibitors and β-blockers in trastuzumab-related cardiotoxicity.

Ohtani K, Ide T, Hiasa KI, Sakamoto I, ... Kubo M, Tsutsui H
Background
Trastuzumab-related cardiotoxicity (TRC) has been considered as reversible. However, recent studies have raised concern against reversibility of left ventricular (LV) systolic dysfunction in breast cancer patients treated with trastuzumab. In addition, the efficacy of medical treatment for heart failure (HF) including renin-angiotensin inhibitors and β-blockers has not been defined in TRC.
Methods and results
We retrospectively studied 160 patients with breast cancer receiving trastuzumab in the adjuvant (n = 129) as well as metastatic (n = 31) settings in our institution from 2006 to 2015. During the median follow-up of 3.5 years, 20 patients (15.5%) receiving adjuvant trastuzumab and 7 patients (22.6%) with metastatic breast cancer developed TRC with a mean decrease in LV ejection fraction (EF) of 19.8%. By the multivariate analysis, lower LVEF before trastuzumab (OR 1.30; 95% CI 1.16-1.48; P = 0.0001) independently predicted subsequent development of TRC. LV systolic dysfunction was reversible in 20 patients (74.1%) with a median time to recovery of 7 months, which was independently associated with lower dose of anthracyclines (OR 1.03; 95% CI 1.01-1.07, P = 0.020) and an introduction of renin-angiotensin inhibitors and β-blockers (OR 19.0; 95% CI 1.00-592.2, P = 0.034).
Conclusions
Irreversible decline in LVEF occurred in patients who underwent trastuzumab in combination with anthracyclines with a relatively high frequency. The lower cumulative dose of anthracyclines and HF treatment including renin-angiotensin inhibitors and β-blockers were both independent predictors to enhance LV functional reversibility in patients with TRC.



Clin Res Cardiol: 29 Sep 2019; 108:1128-1139
Ohtani K, Ide T, Hiasa KI, Sakamoto I, ... Kubo M, Tsutsui H
Clin Res Cardiol: 29 Sep 2019; 108:1128-1139 | PMID: 30859381
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Impact:
Abstract

Three-dimensional speckle-tracking echocardiography for the global and regional assessments of left ventricle myocardial deformation in breast cancer patients treated with anthracyclines.

Coutinho Cruz M, Moura Branco L, Portugal G, Galrinho A, ... Luz R, Cruz Ferreira R
Background
Assessment of 2D/3D left ventricular ejection fraction (LVEF) and 2D global longitudinal strain (GLS) is the gold standard for diagnosing cancer therapeutics-related cardiac dysfunction (CTRCD). Although 3D speckle-tracking echocardiography (STE) has several advantages, it is not used in this setting.
Methods
105 breast cancer patients who underwent serial echocardiographic assessment during anthracycline therapy were included. STE was used to estimate 2D GLS, 3D GLS, 3D global circumferential strain (GCS), 3D global radial strain (GRS), and 3D global area strain (GAS). CTRCD was defined as an absolute decrease in 2D/3D LVEF > 10% to a value < 54% or a relative decrease in 2D GLS > 15%.
Results
24 patients developed CTRCD. There was a significant worsening of all 3D strain parameters during chemotherapy. 3D strain regional analysis showed impaired contractility in the anterior, inferior, and septal walls. Variations of 3D GRS and 3D GCS were associated with a higher incidence of CTRCD and the variation of 3D GRS was an independent predictor of CTRCD. Variations of 3D GCS and 3D GRS had a good discrimination for predicting CTRCD, with optimal cutoff values of - 34.2% for 3D GCS and - 34.4% for 3D GRS. These variations were observed 45 and 23 days before the diagnosis of CTRCD, respectively.
Conclusion
Variations of 3D strain parameters were predictive of and preceded CTRCD, and thus have added value over currently recommended 2D/3D LVEF and 2D GLS. Routine application of this technique should be considered to offer targeted monitoring and timely initiation of cardioprotective treatment.



Clin Res Cardiol: 25 Sep 2019; epub ahead of print
Coutinho Cruz M, Moura Branco L, Portugal G, Galrinho A, ... Luz R, Cruz Ferreira R
Clin Res Cardiol: 25 Sep 2019; epub ahead of print | PMID: 31559482
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Impact:
Abstract

Higher doses of loop diuretics limit uptitration of angiotensin-converting enzyme inhibitors in patients with heart failure and reduced ejection fraction.

Ter Maaten JM, Martens P, Damman K, Dickstein K, ... Voors AA, Mullens W
Background
Loop diuretics are frequently prescribed to patients with heart failure and reduced ejection fraction (HFrEF) for the treatment of congestion; however, they might hamper uptitration of inhibitors of the renin-angiotensin system.
Methods
Loop diuretic dose at baseline was recorded in 2338 patients with HFrEF enrolled in BIOSTAT-CHF, an international study of HF patients on loop diuretic therapy who were eligible for uptitration of angiotensin-converting enzyme inhibitors (ACEi)/mineralocorticoid receptor antagonists (MRA). The association between loop diuretic dose and uptitration of ACEi/MRA to percentage of target dose was adjusted for a previously published model for likelihood of uptitration and a propensity score.
Results
Baseline median loop diuretic dose was 40 [40-100] mg of furosemide or equivalent. Higher doses of loop diuretics were associated with higher NYHA class and higher levels of NT-proBNP, more severe signs and symptoms of congestion, more frequent MRA use, and lower doses of ACEi reached at 3 and 9 months (all P < 0.01). After propensity adjustment, higher doses of loop diuretics remained significantly associated with poorer uptitration of ACEi (Beta per log doubling of loop diuretic dose: - 1.66, P = 0.021), but not with uptitration of MRAs (P = 0.758). Higher doses of loop diuretics were independently associated with an increased risk of all-cause mortality or HF hospitalization [HR per doubling of loop diuretic dose: 1.06 (1.01-1.12), P = 0.021].
Conclusions
Higher doses of loop diuretics limited uptitration of ACEi in patients with HFrEF and were associated with a higher risk of death and/or HF hospitalization, independent of their lower likelihood of uptitration and higher baseline risk. This figure was created with images adapted from Servier Medical Art licensed under a Creative Commons Attribution 3.0.



Clin Res Cardiol: 29 Jan 2020; epub ahead of print
Ter Maaten JM, Martens P, Damman K, Dickstein K, ... Voors AA, Mullens W
Clin Res Cardiol: 29 Jan 2020; epub ahead of print | PMID: 32002631
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Impact:
Abstract

Impact of single-visit American versus European office blood pressure measurement procedure on individual blood pressure classification: a cross-sectional study.

Vischer AS, Socrates T, Winterhalder C, Eckstein J, Mayr M, Burkard T
Objectives
Recently, ACC/AHA and ESC/ESH guidelines defined different office blood pressure measurement (OBPM) procedures and ranges. We aimed to describe the effect of the different methods to calculate OBPM on BP classification.
Methods and results
Four standardised OBPM were performed in 802 patients within a single visit. BP values were calculated (EUR-/US-BPM) and categorised (EUR-/US-Ranges) according to ACC/AHA and ESC/ESH guidelines. Comparing the BPM procedures, the mean absolute difference of systolic and diastolic BP was 4 (SD ± 5) and 3 (SD ± 3) and a difference ≥ 5 mmHg was found in 35% and 16%, respectively. There was an increase of grade 1/2 arterial hypertension of 87% and 120% comparing BP values categorised according to US-Ranges with EUR-Ranges after applying EUR- or US-BPM to all (p < 0.0001), of 25% and 6% comparing BP values calculated according to US-BPM with EUR-BPM applying EUR- or US-Ranges to all (p = 0.006 and p = 0.17), and of 134% comparing US-Ranges/US-BPM with EUR-Ranges/EUR-BPM (p < 0.0001), respectively. Overall, 16% were reclassified to higher categories when applying US-BPM, and 42-45% of patients classified as \"high normal\" applying EUR-BPM procedures were reclassified when applying US-BPM procedure, 76-77% of them to \"hypertensive\" categories.
Conclusion
Besides the effect of the redefinition of BP categories by ACC/AHA, the calculation method of US-BPM compared to EUR-BPM leads to a further relevant increase of patients classified as \"hypertensive\". In addition to the definition of uniform outcome-oriented target BP values, there is an urgent need for a universal definition of an OBPM procedure as prerequisite for proper BP classification and patient management.



Clin Res Cardiol: 30 Aug 2019; 108:990-999
Vischer AS, Socrates T, Winterhalder C, Eckstein J, Mayr M, Burkard T
Clin Res Cardiol: 30 Aug 2019; 108:990-999 | PMID: 30725172
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Impact:
Abstract

Haemodynamic prosthetic valve performance in patients with early leaflet thrombosis after transcatheter aortic valve implantation.

Hein M, Minners J, Jander N, Breitbart P, ... Neumann FJ, Ruile P
Aims
We sought to evaluate haemodynamic prosthetic valve performance in patients with early leaflet thrombosis (LT) after transcatheter aortic valve implantation (TAVI).
Method and results
In this retrospective observational study, 59 patients with LT underwent clinical and echocardiographic follow-up. During a median follow-up of 383 days 41 patients received antiplatelet therapy (APT-group) and 18 patients oral anticoagulation due to atrial fibrillation (AC-group). The mean pressure gradient (MPG) at baseline did not differ between groups (P = 0.875). During follow-up, MPG increased from 11.0 (9.0; 14.5) to 13.0 mmHg (10.0; 18.0)_ in the APT-group (P = 0.010) but remained unchanged in the AC-group (P = 0.297) resulting in a significantly higher MPG in patients on antiplatelet therapy (P = 0.024). Similarly, change of MPG per year was significantly higher in the APT-group [1.4 (- 0.9; 7.0) vs. - 0.6 (- 2.5; 1.1), P = 0.014]. Seven (17.1%) patients in the APT-group and two(11.1%) patients in the AC-group developed MPGs of at least 20 mmHg (P = 0.558). Three patients (7.3%) in the APT- and none in the AC-group developed symptoms of obstructive thrombosis (P = 0.239). In our adjusted analysis, only lack of anticoagulation was significantly associated with change in gradients during follow-up (P = 0.012).
Conclusions
In patients with LT, antiplatelet-, but not anticoagulant therapy, was associated with significant increases in MPG, which may lead to symptomatic obstructive valve thrombosis.



Clin Res Cardiol: 30 Aug 2019; 108:1017-1024
Hein M, Minners J, Jander N, Breitbart P, ... Neumann FJ, Ruile P
Clin Res Cardiol: 30 Aug 2019; 108:1017-1024 | PMID: 30725171
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Impact:
Abstract

Prognostic impact of recurrences of ventricular tachyarrhythmias and appropriate ICD therapies in a high-risk ICD population.

Schupp T, Akin I, Reiser L, Bollow A, ... Borggrefe M, Behnes M
Purpose
The study sought to evaluate the prognostic impact of recurrences of ventricular tachyarrhythmias in consecutive ICD recipients with ventricular tachyarrhythmias on admission.
Methods
All consecutive patients surviving at least one episode of ventricular tachyarrhythmias from 2002 to 2016 and discharged with an ICD (pre-existing ICD or ICD implantation at index hospitalization) were included. The primary endpoint was all-cause mortality according to the presence or absence of recurrences of ventricular tachyarrhythmias at 5 years. Secondary endpoints comprised the impact of different types of recurrences, appropriate ICD therapies, as well as predictors of recurrences and appropriate ICD therapies. Kaplan-Meier, multivariable Cox regression and propensity score matching analyses were applied.
Results
A total of 592 consecutive ICD recipients was included (44% with recurrences of ventricular tachyarrhythmias and 56% without). Recurrences of ventricular tachyarrhythmias were associated with increased all-cause mortality at 5 years (HR = 1.498; 95% CI = 1.052-2.132; p = 0.025). Worst survival was observed in patients with sustained VT or VF as first recurrences compared to non-sustained VT, as well as in patients with cumulative recurrences of non-sustained or sustained VT plus VF, whereas mortality was not affected by the number of recurrences of ventricular tachyarrhythmias (> 4 vs. ≤ 4). Moreover, appropriate ICD therapies were associated with increased all-cause mortality (HR = 1.874; 95% CI = 1.318-2.666; p = 0.001), mainly attributed to secondary preventive ICDs. Finally, atrial fibrillation, LVEF < 35% and non-ischemic cardiomyopathy were identified as predictors of recurrences of ventricular tachyarrhythmias and appropriate ICD therapies.
Conclusions
Recurrences of ventricular tachyarrhythmias and recurrent appropriate ICD therapies are associated with increased long-term all-cause mortality in consecutive ICD recipients. Non-ischemic cardiomyopathy, AF and LVEF < 35% revealed to be significant predictors of both endpoints.



Clin Res Cardiol: 30 Jul 2019; 108:878-891
Schupp T, Akin I, Reiser L, Bollow A, ... Borggrefe M, Behnes M
Clin Res Cardiol: 30 Jul 2019; 108:878-891 | PMID: 30756152
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Impact:
Abstract

Lower mortality in an all-comers aortic stenosis population treated with TAVI in comparison to SAVR.

Möllmann H, Husser O, Blumenstein J, Liebetrau C, ... Achenbach S, Gaede L
Background
Within the last years TAVI-especially transfemoral/transvascular TAVI-has proven to be a valuable therapeutic option for most patients suffering from AS. Here, we present the outcome of a complete dataset of all patients undergoing aortic valve replacement in Germany in 2018.
Methods
The data of all aortic valve procedures performed in Germany in 2018 derive from the mandatory nationwide quality control program. Patients were stratified with a new version of the German Aortic valve score (AKL Score) divided in different risk stratification depending on the treatment with either a catheter based (TV-TAVI) or surgical (iSAVR) approach. In-hospital outcomes have been compared between the two approaches.
Results
19,317 transvascular (TV)-TAVI procedures were carried out. In contrast to this steady growth, the number of iSAVR andtransapical (TA) -TAVI procedures declined. In-hospital mortality after TV-TAVI (2.5%) was lower when compared to iSAVR (3.1%) as well as TA-TAVI (5.7%) in-hospital mortality after TV-TAVI was significantly lowest (Fig. 2) with an in-hospital mortality rate of 2.5%. TV-TAVI was the only approach with an observed vs. expected mortality ratio < 1 according to the used risk prediction model.
Conclusion
TV-TAVI is more often performed and shows lower in-hospital mortality than iSAVR. TV-TAVI has replaced iSAVR as the gold-standard concerning in-hospital outcome in aortic stenosis management.



Clin Res Cardiol: 30 Sep 2019; epub ahead of print
Möllmann H, Husser O, Blumenstein J, Liebetrau C, ... Achenbach S, Gaede L
Clin Res Cardiol: 30 Sep 2019; epub ahead of print | PMID: 31573055
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Impact:
Abstract

Functional neuroimaging in the acute phase of Takotsubo syndrome: volumetric and functional changes of the right insular cortex.

Dichtl W, Tuovinen N, Barbieri F, Adukauskaite A, ... Gizewski ER, Steiger R
Background
A brain-heart interaction has been proposed in Takotsubo syndrome (TTS). Structural changes in the limbic system and hypoconnectivity between certain brain areas in the chronic phase of the disease have been reported, but little is known concerning functional neuroimaging in the acute phase. We hypothesizedh anatomical and functional changes in the central nervous system and investigated whole-brain volumetric and functional connectivity alterations in the acute phase TTS patients compared to controls.
Methods
Anatomical and resting-state functional magnetic resonance imaging were performed in postmenopausal females: thirteen in the acute TTS phase and thirteen healthy controls without evidence of coronary artery disease. Voxel-based morphometry and graph theoretical analysis were applied to identify anatomical and functional differences between patients and controls.
Results
Significantly lower gray matter volumes were found in TTS patients in the right middle frontal gyrus (p = 0.004) and right subcallosal cortex (p = 0.009) compared to healthy controls. When lower threshold was applied, volumetric changes were noted in the right insular cortex (p = 0.0113), the right paracingulate cortex (p = 0.012), left amygdala (p = 0.018), left central opercular cortex (p = 0.017), right (p = 0.013) and left thalamus (p = 0.017), and left cerebral cortex (p = 0.017). Graph analysis revealed significantly (p < 0.01) lower functional connectivity in TTS patients compared to healthy controls, particularly in the connections originating from the right insular cortex, temporal lobes, and precuneus.
Conclusion
In the acute phase of TTS volumetric changes in frontal regions and the central autonomic network (i.e. insula, anterior cingulate cortex, and amygdala) were noted. In particular, the right insula, associated with sympathetic autonomic tone, had both volumetric and functional changes.



Clin Res Cardiol: 29 Jan 2020; epub ahead of print
Dichtl W, Tuovinen N, Barbieri F, Adukauskaite A, ... Gizewski ER, Steiger R
Clin Res Cardiol: 29 Jan 2020; epub ahead of print | PMID: 32002630
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Impact:
Abstract

Two birds with one stone: transcatheter valve-in-valve treatment of a failed surgical bioprosthesis with concomitant severe stenosis and paravalvular leak.

Alvarez-Covarrubias HA, Xhepa E, Michel JM, Kasel AM

Implantation of bioprosthetic surgical valves has been a common procedure in elderly patients with severe aortic stenosis due to patients´ preferences avoiding anticoagulation therapy. However, this valve presents sometime certain deterioration degree (i.e., dysfunction due to stenosis or regurgitation) or even paravalvular leak. Transcatheter heart valve implantation is a good alternative in high-risk patients. The valve-in-valve procedure has been shown to be a safe and effective procedure. However, the presence of the fixed sewing ring of the surgical bioprosthesis can hamper appropriate expansion of the THV. For this reason, the use of cracking balloon seems to be a safe alternative to increase the effective orifice area. We present a case of a patient with a degenerated previous implanted biological valve and paravalvular leak. We used the treatment strategy of valve-in-valve with post-dilatation with high-pressure balloon, in a way to treat both, the degenerated valve and the paravalvular leak. The use of a single percutaneous procedure was enough and safe to treat both problems without further complications.



Clin Res Cardiol: 29 Sep 2019; 108:1069-1073
Alvarez-Covarrubias HA, Xhepa E, Michel JM, Kasel AM
Clin Res Cardiol: 29 Sep 2019; 108:1069-1073 | PMID: 31267238
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Impact:
Abstract

Predictive factors and long-term prognosis of transcatheter aortic valve implantation-associated endocarditis.

Tabata N, Al-Kassou B, Sugiura A, Shamekhi J, ... Nickenig G, Sinning JM
Background
There are still limited data regarding transcatheter aortic valve implantation (TAVI) endocarditis.
Objectives
The objective of the present study was to investigate the predictor and long-term outcome of TAVI endocarditis.
Methods
Consecutive patients undergoing TAVI at the University of Bonn were prospectively enrolled in this study. Transcatheter heart valve (THV) endocarditis was defined according to Duke criteria. The primary outcome was all-cause death within a 5-year follow-up.
Results
1448 successful TAVI patients were eligible for the study and 17 patients (1.2%) developed THV endocarditis during the follow-up period (median 294 days). A multivariable logistic regression analysis identified age (odds ratio [OR] 0.90; P = 0.001) and residual paravalvular leakage (PVL) ≥ 2 after TAVI (OR 5.15; P = 0.015) as the main predictors for the occurrence of TAVI endocarditis. Additional analyses revealed that younger patients were significantly associated with higher rates of diabetes (P = 0.001), hemodialysis (P < 0.001), prior cardiac surgery (P < 0.001), and chronic obstructive pulmonary disease (COPD) (P < 0.001). A Kaplan-Meier analysis showed a significantly worse prognosis in TAVI patients with endocarditis than in patients without (log-rank; P = 0.03) during the 5-year follow-up. A multivariable Cox proportional hazard analysis revealed that TAVI endocarditis is an independent predictor of long-term mortality (hazard ratio 4.17; 95% CI 1.91-9.07; P < 0.001).
Conclusions
Our study identified lower age and residual PVL ≥ 2 as predictors for THV endocarditis, which itself may be considered as an independent predictor of long-term mortality after TAVI.



Clin Res Cardiol: 03 Feb 2020; epub ahead of print
Tabata N, Al-Kassou B, Sugiura A, Shamekhi J, ... Nickenig G, Sinning JM
Clin Res Cardiol: 03 Feb 2020; epub ahead of print | PMID: 32020270
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Impact:
Abstract

Hemodynamics of paradoxical severe aortic stenosis: insight from a pressure-volume loop analysis.

Gotzmann M, Hauptmann S, Hogeweg M, Choudhury DS, ... Bergbauer M, Mügge A
Background
Controversy exists about the pathophysiology of different hemodynamic subgroups of AS. In particular, the mechanism of the paradoxical low-flow, low-gradient (PLFLG) AS with preserved ejection fraction (EF) is unclear.
Methods
A total of 41 patients with severe, symptomatic AS were divided into the following 4 subgroups based on the echocardiographically determined hemodynamics: (1) normal-flow, high-gradient (NFHG) AS; (2) low-flow, high-gradient AS; (3) paradoxical low-flow, low-gradient (PLFLG) AS with preserved EF and (4) low-flow, low-gradient (LFLG) AS with reduced EF. As part of the comprehensive invasive examinations, the analyses of the PV loops were performed with the IntraCardiac Analyzer (CD-Leycom, The Netherlands).
Results
PLFLG was characterized by small left ventricular volumes as well as a decreased cardiac index, a decreased systolic contractility and a lower stroke work, than the conventional NFHG AS. Alterations in effective arterial elastance (2.36 ± 0.67 mmHg/ml in NFHG versus 3.01 ± 0.79 mmHg/ml in PLFLG, p = 0.036) and end-systolic elastance (3.72 ± 1.84 mmHg/ml in NFHG versus 5.53 ± 2.3 mmHg/ml in PLFLG, p = 0.040) indicated impaired vascular function and increased chamber stiffness.
Conclusions
The present study suggests that the hemodynamics of PLFLG AS can be explained by two mechanisms: (1) stiffness of the small left ventricle with reduced contractility, and (2) increased afterload due to the impairment of vascular function. Both mechanisms have similarities to those of heart failure with preserved EF. This type of remodeling may explain the poor prognosis of PLFLG AS.



Clin Res Cardiol: 30 Jul 2019; 108:931-939
Gotzmann M, Hauptmann S, Hogeweg M, Choudhury DS, ... Bergbauer M, Mügge A
Clin Res Cardiol: 30 Jul 2019; 108:931-939 | PMID: 30737530
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Impact:
Abstract

Circulatory factors associated with function and prognosis in patients with severe heart failure.

Rullman E, Melin M, Mandić M, Gonon A, Fernandez-Gonzalo R, Gustafsson T
Background
Multiple circulatory factors are increased in heart failure (HF). Many have been linked to cardiac and/or skeletal muscle tissue processes, which in turn might influence physical activity and/or capacity during HF. This study aimed to provide a better understanding of the mechanisms linking HF with the loss of peripheral function.
Methods and results
Physical capacity measured by maximum oxygen uptake, myocardial function (measured by echocardiography), physical activity (measured by accelerometry), and mortality data was collected for patients with severe symptomatic heart failure an ejection fraction < 35% (n = 66) and controls (n = 28). Plasma circulatory factors were quantified using a multiplex immunoassay. Multivariate (orthogonal projections to latent structures discriminant analysis) and univariate analyses identified many factors that differed significantly between HF and control subjects, mainly involving biological functions related to cell growth and cell adhesion, extracellular matrix organization, angiogenesis, and inflammation. Then, using principal component analysis, links between circulatory factors and physical capacity, daily physical activity, and myocardial function were identified. A subset of ten biomarkers differentially expressed in patients with HF vs controls covaried with physical capacity, daily physical activity, and myocardial function; eight of these also carried prognostic value. These included established plasma biomarkers of HF, such as NT-proBNP and ST2 along with recently identified factors such as GDF15, IGFBP7, and TfR, as well as a new factor, galectin-4.
Conclusions
These findings reinforce the importance of systemic circulatory factors linked to hemodynamic stress responses and inflammation in the pathogenesis and progress of HF disease. They also support established biomarkers for HF and suggest new plausible markers.



Clin Res Cardiol: 26 Sep 2019; epub ahead of print
Rullman E, Melin M, Mandić M, Gonon A, Fernandez-Gonzalo R, Gustafsson T
Clin Res Cardiol: 26 Sep 2019; epub ahead of print | PMID: 31562542
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Impact:
Abstract

Optimizing heart failure treatment following cardiac resynchronization therapy.

Jorsal A, Pryds K, McMurray JJV, Wiggers H, ... Nielsen JC, Nielsen RR
Background
Device therapy in addition to medical treatment improves prognosis in a subset of patients with heart failure and reduced ejection fraction. However, some patients remain symptomatic or their heart failure even progresses despite cardiac resynchronization therapy (CRT). The aim of the study was to evaluate the proportion of patients who could benefit from optimization of medical therapy using sacubitril/valsartan, ivabradine, or both following CRT implantation.
Methods
We conducted a post hoc analysis of a single-centre, patient and outcome-assessor blinded, randomized-controlled trial, in which patients scheduled for CRT were randomized to empiric (n = 93) or imaging-guided left-ventricular lead placement (n = 89). All patients underwent clinical evaluation and blood sampling at baseline and 6 months following CRT implantation. The proportion of patients meeting the indication for sacubitril/valsartan (irrespective of angiotensin-converting enzyme inhibitor or angiotensin 2 receptor blocker dosage) and/or ivabradine according to current guidelines was evaluated at baseline and after 6 months.
Results
Of 182 patients with an indication for CRT, 146 (80%) also had an indication for optimization of medical therapy at baseline by adding sacubitril/valsartan, ivabradine, or both. Of the 179 survivors at 6 months, 136 (76%) were still symptomatic after device implantation; of these, 51 (38%) patients had an indication for optimization of medical therapy: sacubitril/valsartan in 37 (27%), ivabradine in 7 (5%), and both drugs in 7 (5%) patients. Seven (18%) patients without indication at baseline developed an indication for medical optimization 6 months after CRT implantation.
Conclusion
In the present study, 38% of those who remained symptomatic 6 months after CRT implantation were eligible for optimization of medical therapy with sacubitril/valsartan, ivabradine, or both. Patients with CRT may benefit from systematic follow-up including evaluation of medical treatment.



Clin Res Cardiol: 25 Sep 2019; epub ahead of print
Jorsal A, Pryds K, McMurray JJV, Wiggers H, ... Nielsen JC, Nielsen RR
Clin Res Cardiol: 25 Sep 2019; epub ahead of print | PMID: 31559483
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Impact:
Abstract

Temporal trends in incidence and outcome of acute coronary syndrome.

Neumann JT, Goßling A, Sörensen NA, Blankenberg S, Magnussen C, Westermann D
Background
We aimed to investigate changes of incidence, outcome and related interventions of patients with acute coronary syndrome (ACS) over the past decade in Germany.
Methods
Data on the international statistical classification of diseases and procedural codes from the Federal Bureau of Statistics in Germany was used. This included all ACS cases in Germany in the years 2005-2015. Analyses were performed separately for the diagnoses of overall ACS, ST-elevation myocardial infarction (MI), non-ST-elevation MI and unstable angina pectoris. Procedures including coronary angiography and percutaneous coronary intervention and the endpoint in-hospital mortality were assessed.
Results
Between 2005 and 2015 a total of 3797,546 cases of ACS were recorded. The mean age was 69 years and 36% were females. In-hospital mortality was 6.3%, 62% underwent coronary angiography and 42% received percutaneous coronary intervention. In-hospital mortality was highest for patients with ST-elevation MI (12.0%) and lowest for patients with unstable angina pectoris (0.6%). From 2005 to 2015 the incidence rates of ACS, ST-elevation MI and unstable angina pectoris decreased, while the incidence rate of non-ST-elevation MI increased. The percentages of performed coronary angiographies and percutaneous coronary interventions increased from 52 to 70% and 34 to 50%, respectively. The adjusted incidence rate of in-hospital mortality decreased from 64.9 cases per 1000 person-years to 54.8 cases.
Conclusion
In a large dataset including more than 3.7 million cases, we report an increase in coronary procedures and a reduction of ACS incidence and related mortality in the past decade in Germany.



Clin Res Cardiol: 06 Feb 2020; epub ahead of print
Neumann JT, Goßling A, Sörensen NA, Blankenberg S, Magnussen C, Westermann D
Clin Res Cardiol: 06 Feb 2020; epub ahead of print | PMID: 32034482
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Impact:
Abstract

Outcomes in patients with dual antegrade conduction in the atrioventricular node: insights from a multicentre observational study.

Hartmann J, Jungen C, Stec S, Klatt N, ... Martinek M, Meyer C
Background
Supraventricular tachycardias induced by dual antegrade conduction via the atrioventricular (AV) node are rare but often misdiagnosed with severe consequences for the affected patients. As long-term follow-up in these patients was not available so far, this study investigates outcomes in patients with dual antegrade conduction in the AV node.
Methods and results
In this multicentre observational study, patients from six European centres were studied. Catheter ablation was performed in 17 patients (52 ± 16 years) with dual antegrade conduction via both AV nodal pathways between 2012 and 2018. Patients with the final diagnosis of a manifest dual AV nodal non-re-entrant tachycardia had a mean delay of the correct diagnosis of over 1 year (range 2-31 months). Two patients received prescription of non-indicated oral anticoagulation, two further patients suffered from inappropriate shocks of an implantable cardioverter defibrillator. In 12 patients, a co-existence of dual antegrade and re-entry conduction in the AV node was present. Mean fast pathway conduction time was 138 ± 61 ms and mean slow pathway conduction time was 593 ± 134 ms. Successful radiofrequency catheter ablation was performed in all patients. Post-procedurally oral anticoagulation was discontinued, without detection of cerebrovascular events or atrial fibrillation during a long-term follow-up of median 17 months (range 6-72 months).
Conclusion
This first multicentre study investigating patients with supraventricular tachycardia and dual antegrade conduction in the AV node demonstrates that catheter ablation is safe and effective while long-term patient outcome is good. Autonomic tone dependent changes in ante- vs. retrograde conduction via slow and/or fast pathway can challenge the diagnosis and therapy in some patients.



Clin Res Cardiol: 29 Jan 2020; epub ahead of print
Hartmann J, Jungen C, Stec S, Klatt N, ... Martinek M, Meyer C
Clin Res Cardiol: 29 Jan 2020; epub ahead of print | PMID: 32002633
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Abstract

Sacubitril/valsartan reduces ventricular arrhythmias in parallel with left ventricular reverse remodeling in heart failure with reduced ejection fraction.

Martens P, Nuyens D, Rivero-Ayerza M, Van Herendael H, ... Dupont M, Mullens W
Background
Sacubitril/valsartan reduced the occurrence of sudden cardiac death in the PARADIGM-HF trial. However, limited information is available about the mechanism.
Methods
Heart failure (HF)-patients receiving sacubitril/valsartan for a class-I indication equipped with an implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRT) with remote tele-monitoring were retrospectively analyzed. Device-registered arrhythmic-events were determined [ventricular tachycardia/fibrillation (VT/VF), appropriate therapy, non-sustained VT (NsVT; > 4beats and < 30 s), hourly premature ventricular contraction (PVC)-burden], following sacubitril/valsartan initiation (incident-analysis) and over an equal time period before initiation (antecedent-analysis). Reverse remodeling to sacubitril/valsartan was defined as an improvement of left ventricular ejection fraction of ≥ 5% between baseline and follow-up.
Results
A-total of 151 HF-patients with reduced LVEF (29 ± 9%) were included. Patients were switched from ACE-I or ARB to equal doses of sacubitril/valsartan (expressed as %-target-dose; before = 58 ± 30% vs. after = 56 ± 27%). The mean follow-up of both the incident and antecedent analysis was 364 days. Following the initiation, VT/VF-burden dropped (individual patients with VT/VF pre_n = 19 vs. post_n = 10, total-episodes of VT/VF pre_n = 51 vs. post_n = 14, both p < 0.001), resulting in reduced occurrence of appropriate therapy (pre_n = 16 vs. post_n = 6; p < 0.001). NsVT-burden per patient also dropped (mean episodes pre_n = 7.7 ± 11.8 vs. post_n = 3.7 ± 5.4; p < 0.001). There was no impact on atrial-fibrillation burden. PVC-burden dropped significantly which was associated with an improvement in BiV-pacing in patients with < 90% BiV-pacing at baseline. A higher degree of reverse remodeling was associated with a lower burden of NsVT and PVCs (both p < 0.05).
Conclusion
Initiation of sacubitril/valsartan is associated with a lower degree of VT/VF, resulting in less ICD-interventions. This beneficial effect on ventricular arrhythmias might be related to cardiac reverse remodeling.



Clin Res Cardiol: 29 Sep 2019; 108:1074-1082
Martens P, Nuyens D, Rivero-Ayerza M, Van Herendael H, ... Dupont M, Mullens W
Clin Res Cardiol: 29 Sep 2019; 108:1074-1082 | PMID: 30788621
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Abstract

Left ventricular geometry and function in early repolarization: results from the population-based Gutenberg Health Study.

Trenkwalder T, Rübsamen N, Schmitt VH, Arnold N, ... Reinhard W, Schnabel R
Aims
The electrocardiographic pattern of early repolarization (ER) is related to increased cardiac mortality in the general population. The pathophysiological basis of ER is largely unknown. We investigated the association of echocardiographic structural and functional parameters of the left ventricle with the presence of ER in the community.
Methods and results
The presence of ER (ER+) was assessed in 13,878 participants (mean age 54.6 years, 51.1% women) of the Gutenberg Health Study and related to left ventricular structure and function derived from standard echocardiography. The prevalence of ER was 5.0% (694/13,878), with higher prevalence in men than women (6.6% vs. 3.5%, p < 0.001). In men baseline characteristics differed including a lower BMI and a lower heart rate in ER+ individuals, whereas in women there were only minor differences. Multivariable-adjusted logistic regression analysis in men showed an association of ER with smaller diameters (left-ventricular end-diastolic diameter: OR 0.77 95% CI 0.69-0.86, p < 0.001; left-ventricular end-systolic diameter: OR 0.86 95% CI 0.78-0.95, p = 0.0035), and lower left-ventricular end-diastolic and end-systolic volume (OR 0.72 95% CI 0.65, 0.80, p < 0.001 and OR 0.80 95% CI 0.72, 0.89, p < 0.001). In women, the associations of ER with left ventricular diameters and volumes showed a similar direction, but were not as pronounced.
Conclusion
In the community, the ER pattern predominantly occurs in men with a low heart rate and a slender habit. Furthermore, ER is not associated with higher left ventricular mass or size but rather with smaller left ventricular diameters and volumes with a regular systolic and diastolic function. Patterns were comparable in women, but less strong.



Clin Res Cardiol: 29 Sep 2019; 108:1107-1116
Trenkwalder T, Rübsamen N, Schmitt VH, Arnold N, ... Reinhard W, Schnabel R
Clin Res Cardiol: 29 Sep 2019; 108:1107-1116 | PMID: 30820639
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Impact:
Abstract

Performance of the entirely subcutaneous ICD in borderline indications.

Willy K, Reinke F, Bögeholz N, Köbe J, Eckardt L, Frommeyer G
Background
The subcutaneous ICD (S-ICDâ„¢) is an important advance in device therapy for prevention of sudden cardiac death (SCD). In some patients, decision pro- or contra-ICD implantation is particularly challenging due to inconsistent data on risk of ventricular tachyarrhythmias or sudden cardiac death, rare entities, special medical or family history, or patients\' wishes. Whether decision-making in these borderline cases has been facilitated with the new option of a S-ICDâ„¢ is unknown.
Material and methods
All patients with an implanted S-ICD™ without a class I or IIa recommendation for primary prophylaxis of sudden cardiac death in the current guidelines (n = 30 patients) in our large-scaled single-centre S-ICD™ registry (n = 249 patients) were included in this study. Baseline characteristics, appropriate and inappropriate shocks, and complications were documented in a mean follow-up of 40 months.
Results
In all patients S-ICD™ implantation was performed for primary prevention of SCD. Of all 30 patients with an overall mean age of 40.5 ± 15.6 years, 17 were male (57%). The mean left ventricular ejection fraction (LVEF) was 54.5 ± 9.9%. Indication were highly variable and ranged from structural heart disease, nsVT and LV-EF > 35% to patients with polymorphic non-sustained ventricular tachycardia (nsVT) and suspect syncope. During follow-up, six episodes of sustained ventricular tachyarrhythmias and four episodes of ventricular fibrillation (VF) were adequately terminated in three patients (10%). Two of these patients were implanted for polymorphic nsVT and previous syncope without structural heart disease. In three patients, T-wave-oversensing and in one patient also P-wave-oversensing resulted in an inappropriate shock (five in total), two additional episodes of oversensing ended before shock delivery. There were no S-ICD™ system-related infections. In five patients S-ICD™ replacement was performed due to battery depletion (four regular, one premature). In five patients, ablation procedures were performed after implantation (four because of frequent symptomatic ventricular extra beats, one because of atrial flutter). Change to a transvenous system was necessary in two patients due to need for antibradycardia pacing.
Conclusion
The use of the S-ICDâ„¢ was safe in patients with borderline or unclear indication for ICD implantation in our study. Of note, during a relatively short mean follow-up there were several appropriate therapies, especially for VF in these patients. On the other hand, oversensing also occurred in about 10% of patients, while lead problems were not problematic in this collective. S-ICDâ„¢ implantation may be considered as a possible alternative in cases of borderline indications and clinical uncertainty when decision pro-ICD implantation is made. Incidence of arrhythmias was quite high and mostly consisted of VF. Nevertheless, patient education seems even more important as there is a considerable risk for inappropriate therapies as well.



Clin Res Cardiol: 03 Oct 2019; epub ahead of print
Willy K, Reinke F, Bögeholz N, Köbe J, Eckardt L, Frommeyer G
Clin Res Cardiol: 03 Oct 2019; epub ahead of print | PMID: 31586219
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Impact:
Abstract

Expert consensus document on the assessment of the severity of aortic valve stenosis by echocardiography to provide diagnostic conclusiveness by standardized verifiable documentation.

Hagendorff A, Knebel F, Helfen A, Knierim J, ... Fehske W, Ewen S

According to recent recommendations on echocardiographic assessment of aortic valve stenosis direct measurement of transvalvular peak jet velocity, calculation of transvalvular mean gradient from the velocities using the Bernoulli equation and calculation of the effective aortic valve area by continuity equation are the appropriate primary key instruments for grading severity of aortic valve stenosis. It is obvious that no gold standard can be declared for grading the severity of aortic stenosis. Thus, conclusions of the exclusive evaluation of aortic stenosis by Doppler echocardiography seem to be questionable due to the susceptibility to errors caused by methodological limitations, mathematical simplifications and inappropriate documentation. The present paper will address practical issues of echocardiographic documentation to satisfy the needs to analyze different scenarios of aortic stenosis due to various flow conditions and pressure gradients. Transesophageal and multidimensional echocardiography should be implemented for reliable measurement of geometric aortic valve area and of cardiac dimensions at an early stage of the diagnostic procedure to avoid misinterpretation due to inconsistent results.



Clin Res Cardiol: 02 Sep 2019; epub ahead of print
Hagendorff A, Knebel F, Helfen A, Knierim J, ... Fehske W, Ewen S
Clin Res Cardiol: 02 Sep 2019; epub ahead of print | PMID: 31482241
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Impact:
Abstract

Passive leg-lifting in heart failure patients predicts exercise-induced rise in left ventricular filling pressures.

Tossavainen E, Wikström G, Henein MY, Lundqvist M, Wiklund U, Lindqvist P
Aim
The aim of this study was to assess PCWP with passive leg-lifting (PLL) and exercise, in two groups of patients presenting with normal left ventricular ejection fraction (LVEF); one group with elevated NT-proBNP (eBNP), and one with normal NT-proBNP (nBNP) plasma concentration.
Methods and results
Fifty-one patients with eBNP (NT-proBNP ≥ 125 ng/l) and LVEF > 50%, were investigated and compared with 34 patients with nBNP (NT-proBNP < 125 ng/l) and LVEF > 50%. Both groups underwent right heart catheterization (RHC) at rest, PLL and exercise. From RHC, mean pulmonary arterial pressure (mPAP), cardiac output (CO), and PCWP were measured. All nBNP patients had PCWP < 15 mmHg at rest, and a PCWP of < 25 mmHg with PLL and during exercise. Patients with eBNP had higher (p < 0.01) resting mPAP, PCWP, and mPAP/CO. These values increased with exercise; however, CO increased less in comparison with nBNP patients (p = 0.001). 20% of patients with eBNP had a PCWP > 15 mmHg at rest, this percentage increased to 47% with PLL and 41% had a PCWP > 25 mmHg during exercise. Of those with PCWP > 25 mmHg during exercise, 91% had a PCWP > 15 mmHg with PLL. A PCWP > 15 mmHg on PLL had a 91% sensitivity and 92% specificity in predicting exercise-induced PCWP of > 25 mmHg.
Conclusion
In patients presenting with eBNP, PLL can predict which patients will develop elevated PCWP with exercise. These findings highlight the role of stress assessment.



Clin Res Cardiol: 30 Jul 2019; epub ahead of print
Tossavainen E, Wikström G, Henein MY, Lundqvist M, Wiklund U, Lindqvist P
Clin Res Cardiol: 30 Jul 2019; epub ahead of print | PMID: 31368000
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Impact:
Abstract

Qualitative and quantitative neointimal characterization by optical coherence tomography in patients presenting with in-stent restenosis.

Xhepa E, Byrne RA, Rivero F, Rroku A, ... Alfonso F, Kastrati A
Aims
To describe optical coherence tomography (OCT) findings in patients with in-stent restenosis (ISR) and determine predictors of neointimal patterns and neoatherosclerosis.
Methods and results
Patients undergoing OCT prior to PCI for ISR in three European centres were included. Analyses were performed in a core laboratory. Qualitative and quantitative [gray-scale signal intensity (GSI)] neointima analyses were performed on a per quadrant basis. A total of 107 patients were included. Predominantly homogeneous lesions included 4.5% (0.0-14.3) non-homogeneous quadrants, while predominantly non-homogeneous ones included 28.1% (20.3-37.5) homogeneous quadrants. Mean GSI values differed significantly between homogeneous [108.4 (92.5-123.6)], non-homogeneous [79.9 (61.2-95.9)], and neoatherosclerosis [88.3 (72.8-104.9)] quadrants (p < 0.001 for all comparisons). Stent underexpansion was observed in 48.5% and 61.1% of lesions, respectively (p = 0.225). Female sex and maximal neointimal thickness independently correlate with a non-homogeneous pattern, while angiographic pattern and diabetes mellitus inversely correlate with such pattern. Time from index stenting procedure was the only independent predictor of neoatherosclerosis.
Conclusions
Different neointimal patterns coexist in a significant proportion of ISR lesions. GSI values differ significantly between neointimal categories. Neoatherosclerosis is a time-dependent phenomenon, displaying different time courses in DES compared to BMS, with earlier appearance in the former group. Stent underexpansion is a frequent finding in patients with ISR.



Clin Res Cardiol: 30 Aug 2019; 108:1059-1068
Xhepa E, Byrne RA, Rivero F, Rroku A, ... Alfonso F, Kastrati A
Clin Res Cardiol: 30 Aug 2019; 108:1059-1068 | PMID: 30783752
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Impact:
Abstract

Role of pregnancy hormones and hormonal interaction on the maternal cardiovascular system: a literature review.

Kodogo V, Azibani F, Sliwa K

Hormones have a vital duty in the conservation of physiological cardiovascular function during pregnancy. Alterations in oestrogen, progesterone and prolactin levels are associated with changes in the cardiovascular system to support the growing foetus and counteract pregnancy stresses. Pregnancy hormones are, however, also linked to numerous pathophysiological outcomes on the cardiovascular system. The expression and effects of the three main pregnancy hormones (oestrogen, prolactin and progesterone) vary depending on the gestation period. However, the reaction of a target cell also depends on the abundance of hormone receptors and impacts put forth by other hormones. Hormonal interaction may be synergistic, antagonistic or permissive. It is crucial to explore the cross talk of pregnancy hormones during gestation, as this may have a greater impact on the overall changes to the cardiovascular system.



Clin Res Cardiol: 30 Jul 2019; 108:831-846
Kodogo V, Azibani F, Sliwa K
Clin Res Cardiol: 30 Jul 2019; 108:831-846 | PMID: 30806769
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Impact:
Abstract

Medical treatment of octogenarians with chronic heart failure: data from CHECK-HF.

Linssen GCM, Veenis JF, Kleberger A, Grosfeld MJW, ... Brugts JJ,
Background
Elderly heart failure (HF) patients are underrepresented in clinical trials, though are a large proportion of patients in real-world practice. We investigated practice-based, secondary care HF management in a large group of chronic HF patients aged ≥ 80 years (octogenarians).
Methods
We analyzed electronic health records of 3490 octogenarians with chronic HF at 34 Dutch outpatient clinics in the period between 2013 and 2016 , 49% women. Study patients were divided into HFpEF [LVEF ≥ 50%; n = 911 (26.1%)], HFrEF [LVEF < 40%; n = 2009 (57.6%)] and HF with mid-range EF [HFmrEF: LVEF 40-49%; n = 570 (16.3%)].
Results
Most HFrEF patients aged ≥ 80 years received a beta blocker and a renin-angiotensin system (RAS) inhibitor (angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker), i.e. 78.3% and 72.8% respectively, and a mineralocorticoid receptor antagonist (MRA) was prescribed in 52.0% of patients. All three of these guideline-recommended medications (triple therapy) were given in only 29.9% of octogenarians with HFrEF, and at least 50% of target doses of triple therapy, beta blockers, RAS inhibitor and MRA, were prescribed in 43.8%, 62.2% and 53.5% of the total group of HFrEF patients. Contraindications or intolerance for beta blockers was present in 3.5% of the patients, for RAS inhibitors and MRAs in, 7.2% and 6.1% Conclusions: The majority of octogenarians with HFrEF received one or more guideline-recommended HF medications. However, triple therapy or target doses of the medications were prescribed in a minority. Comorbidities and reported contraindications and tolerances did not fully explain underuse of recommended HF therapies.



Clin Res Cardiol: 05 Feb 2020; epub ahead of print
Linssen GCM, Veenis JF, Kleberger A, Grosfeld MJW, ... Brugts JJ,
Clin Res Cardiol: 05 Feb 2020; epub ahead of print | PMID: 32030498
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Impact:
Abstract

Relation of lowering door-to-balloon time and mortality in ST segment elevation myocardial infarction patients undergoing percutaneous coronary intervention.

Zahler D, Lee-Rozenfeld K, Ravid D, Rozenbaum Z, ... Keren G, Shacham Y
Background
Current guidelines for the treatment of ST-segment elevation myocardial infarction (STEMI) recommend a door-to-balloon time (DBT) of ≤ 90 min for patients undergoing primary percutaneous coronary intervention (PCI). We aimed to investigate the possible impact of further reduction in DBT intervals beyond the 90 min cutoff on short and long-term outcomes among STEMI patients undergoing primary PCI.
Methods
We retrospectively studied 889 STEMI patients (median age 61 years, 83% men) who underwent successful primary PCI and had a DBT of ≤ 90 min. Patients were stratified according to DBT into 2 groups: < 60 min and 60-90 min. Patients records were assessed for the occurrence of in-hospital complications, 30-day and 1-year mortality.
Results
Patients having DBT < 60 min (n = 608, 68%) were more likely to present earlier, in daytime and weekdays, and had better post-procedural left ventricular ejection fraction and lower 30-day mortality (3% vs. 6%, p = 0.03). Mortality over 1-year was significantly lower among patients having DBT < 60 compared to DBT of 60-90 min (4.6% vs. 9.6%, p = 0.004). In a binary logistic regression model DBT < 60 min was associated with 51% risk reduction for 1-year mortality (OR 0.49, 95% CI 0.25-0.93, p = 0.03).
Conclusions
Among STEMI patients undergoing primary PCI within 90 min of admission DBT < 60 min was independently associated with better 1-year mortality.



Clin Res Cardiol: 30 Aug 2019; 108:1053-1058
Zahler D, Lee-Rozenfeld K, Ravid D, Rozenbaum Z, ... Keren G, Shacham Y
Clin Res Cardiol: 30 Aug 2019; 108:1053-1058 | PMID: 30778668
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Impact:
Abstract

Authorship: from credit to accountability. Reflections from the Editors\' Network.

Alfonso F, Zelveian P, Monsuez JJ, Aschermann M, ... Shumakov V,

The Editors\' Network of the European Society of Cardiology provides a dynamic forum for editorial discussions and endorses the recommendations of the International Committee of Medical Journal Editors (ICMJE) to improve the scientific quality of biomedical journals. Authorship confers credit and important academic rewards. Recently, however, the ICMJE emphasized that authorship also requires responsibility and accountability. These issues are now covered by the new (fourth) criterion for authorship. Authors should agree to be accountable and ensure that questions regarding the accuracy and integrity of the entire work will be appropriately addressed. This review discusses the implications of this paradigm shift on authorship requirements with the aim of increasing awareness on good scientific and editorial practices.



Clin Res Cardiol: 29 Jun 2019; 108:723-729
Alfonso F, Zelveian P, Monsuez JJ, Aschermann M, ... Shumakov V,
Clin Res Cardiol: 29 Jun 2019; 108:723-729 | PMID: 31041501
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Impact:
Abstract

Long-term follow-up of implantable cardioverter-defibrillators in Short QT syndrome.

El-Battrawy I, Besler J, Ansari U, Liebe V, ... Borggrefe M, Akin I
Background
Short QT syndrome (SQTS) is associated with sudden cardiac death and implantable cardioverter-defibrillator (ICD) implantation is recommended in this rare disease. However, only a few SQTS families have been reported in literature with limited follow-up data.
Objectives
In the recent study, we describe the outcome data of 57 SQTS patients receiving ICD implantation. This includes seven SQTS families consecutively admitted to our hospital between 2002 and 2017 as well as patients reported in published literature.
Methods
Seven SQTS patients admitted to our hospital were followed up. Additionally, 7 studies out of a total of 626 researched articles were identified through systematic database search (PubMed, Web of Science, Cochrane Library, and Cinahl) and their data analyzed according to our model.
Results
Complications during a median follow-up time of 67.4 months (IQR 6-162 months) were documented in 31 (54%) patients. Inappropriate shocks were seen in 33% due to T wave oversensing (8.7%), supraventricular tachycardia (19%), lead failure and fracture (21%). Further complications were infection (10%), battery depletion (7%) and psychological distress (3.5%). Appropriate shocks were documented in 19%. Three patients (5%) were treated with s-ICD due to recurrent complications of transvenous ICD.
Conclusion
ICD therapy is an effective therapy in SQTS patients. However, it is also associated with significant risk of device-related complications.



Clin Res Cardiol: 29 Sep 2019; 108:1140-1146
El-Battrawy I, Besler J, Ansari U, Liebe V, ... Borggrefe M, Akin I
Clin Res Cardiol: 29 Sep 2019; 108:1140-1146 | PMID: 30879093
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Impact:
Abstract

Catheter ablation in highly symptomatic Brugada patients: a Dutch case series.

Haanschoten DM, Elvan A, Postema PG, Smit JJJ, ... Crijns HJGM, Wilde AAM
Aims
In the past few years, promising results were described in targeting the arrhythmogenic substrate of the epicardial right ventricular outflow tract (RVOT) region in patients with Brugada syndrome (BrS). In this report, we describe our experience with endo- and epicardial substrate mapping and ablation in a series of highly symptomatic BrS patients.
Methods
This case series consists of seven patients with clinical BrS diagnosis who underwent catheter ablation in two Dutch hospitals (Isala hospital Zwolle; and Amsterdam University Medical Centre, location AMC, Amsterdam) and Hamad Heart Hospital in Qatar between 2013 and 2017. All patients had an ICD and recurrent ventricular arrhythmia (VA) episodes. All patients underwent endo-and epicardial mapping of the RVOT region. Elimination of all abnormal potentials and disappearance of BrS ECG pattern during the ablation procedure was the aimed endpoint.
Results
The study group consisted of seven patients with mean age 45.6 ± 16.9 years. Five patients had SCN5A mutations. One patient was excluded from analysis, since ablation could not be performed due to a very large low-voltage area and was later diagnosed with arrhythmogenic right ventricular cardiomyopathy, associated with an SCN5A mutation. One patient underwent both endo- and epicardial ablation to eliminate VA. During a mean follow-up of 3.6 ± 1.5 years, 5/6 patients remained VA free with two patients continuing quinidine.
Conclusion
In patients with BrS and drug-refractory VA, ablation of the arrhythmogenic substrate in the RVOT region was associated with excellent long-term VA-free survival. The majority of these highly symptomatic BrS patients had an SCN5A mutation and also low-voltage areas epicardially.



Clin Res Cardiol: 01 Sep 2019; epub ahead of print
Haanschoten DM, Elvan A, Postema PG, Smit JJJ, ... Crijns HJGM, Wilde AAM
Clin Res Cardiol: 01 Sep 2019; epub ahead of print | PMID: 31478073
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Impact:
Abstract

Are atrial high rate episodes (AHREs) a precursor to atrial fibrillation?

Khan AA, Boriani G, Lip GYH

Atrial high rate episodes (AHREs), also termed, subclinical atrial tachyarrhythmias or subclinical atrial fibrillation (AF) are an important cardiovascular condition. Advancement in implantable cardiac devices such as pacemakers or internal cardiac defibrillators has enabled the continuous assessment of atrial tachyarrhythmias in patients with an atrial lead. Patients with device-detected AHREs are at an elevated risk of stroke and may have unmet anticoagulation needs. While the benefits of oral anticoagulation for stroke prevention in patients with clinical AF are well recognised, it is not known whether the same risk-benefit ratio exists for anticoagulation therapy in patients with AHREs. The occurrence and significance of AHRE are increasingly acknowledged but these events are still not often acted upon in patients presenting with stroke and TIA. Additionally, patients with AHRE show a significant risk for major adverse cardiovascular events (MACE) including acute heart failure, myocardial infarction, cardiovascular hospitalisation, ventricular tachycardia/fibrillation, which is dependent on AHRE burden. In this review, we present an overview of this relatively new entity, its associated thromboembolic risk and its management implications.



Clin Res Cardiol: 13 Sep 2019; epub ahead of print
Khan AA, Boriani G, Lip GYH
Clin Res Cardiol: 13 Sep 2019; epub ahead of print | PMID: 31522249
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Impact:
Abstract

A comparison of procedural success rate and long-term clinical outcomes between in-stent restenosis chronic total occlusion and de novo chronic total occlusion using multicenter registry data.

Lee SH, Cho JY, Kim JS, Lee HJ, ... Lim DS, Yu CW
Background
There have been little data about outcomes of percutaneous coronary intervention (PCI) for in-stent restenosis (ISR) chronic total occlusion (CTO) in the drug eluting stent (DES) era. This study aimed to compare the procedural success rate and long-term clinical outcomes of ISR CTO and de novo CTO.
Methods and results
Patients who underwent PCI for ISR CTO (n = 164) versus de novo CTO (n = 1208) were enrolled from three centers in Korea between January 2008 and December 2014. Among a total of ISR CTO, a proportion of DES ISR CTO was 79.3% (n = 130). The primary outcome was major adverse cardiac events (MACEs); a composite of all-cause death, non-fatal myocardial infarction (MI), or target lesion revascularization (TLR). Following propensity score-matching (1:3), the ISR CTO group (n = 156) had a higher success rate (84.6% vs. 76.0%, p = 0.035), mainly driven by high success rate of PCI for DES ISR CTO (88.6%), but showed a higher incidence of MACEs [hazard ratio (HR): 2.06; 95% confidence interval (CI) 1.37-3.09; p < 0.001], mainly driven by higher prevalence of MI [HR: 9.71; 95% CI 2.06-45.81; p = 0.004] and TLR [HR: 3.04; 95% CI 1.59-5.81; p = 0.001], during 5 years of follow-up after successful revascularization, as compared to the de novo CTO group (n = 408).
Conclusion
The procedural success rate was higher in the ISR CTO than the de novo CTO, especially in DES ISR CTO. However, irrespective of successful revascularization, the long-term clinical outcomes for the ISR CTO were significantly worse than those for the de novo CTO, in terms of MI and TLR.



Clin Res Cardiol: 23 Sep 2019; epub ahead of print
Lee SH, Cho JY, Kim JS, Lee HJ, ... Lim DS, Yu CW
Clin Res Cardiol: 23 Sep 2019; epub ahead of print | PMID: 31552494
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Impact:
Abstract

Cardiac surgery 2018 reviewed.

Doenst T, Bargenda S, Kirov H, Moschovas A, ... Diab M, Faerber G

For the year 2018, more than 22,000 published references can be found in PubMed when entering the search term \"cardiac surgery\". As in the last 4 years, this review focusses on conventional cardiac surgery publications which provide important and interesting information especially relevant for non-surgical colleagues. Interventional techniques have been considered if they were published in the context of classic surgical techniques. We have again reviewed the fields of coronary revascularization and valve surgery and briefly touched on aortic surgery and surgery for terminal heart failure. For revascularization of complex coronary artery disease, bypass grafting was reconfirmed as gold standard and computer-tomographic angiography established equipoise for decision-making with classic angiography. For aortic valve treatment, some new longer-term outcomes from TAVI vs. SAVR trials confirmed equipoise of both treatments for high and medium risk. New information was provided for INR-management of mechanical aortic valves as well as long-term experiences for alternatives to mechanical valves (i.e., Ross and the relatively new Ozaki procedure). In the mitral and tricuspid field, prevalence data illustrate a significant amount of under-treatment for mitral and tricuspid valve regurgitation and evidence for life prolonging-effects of surgery. Finally, elongation of the ascending aorta was identified as new risk factor for aortic dissection and 2 years outcome of the newest generation of left ventricular assist devices demonstrate impressive improvements in outcome. While this article attempts to summarize the most pertinent publications, it does not expect to be complete and cannot be free of individual interpretation. As in recent years, it provides a condensed summary that is intended to give the reader \"solid ground\" for up-to-date decision-making in cardiac surgery and a stimulus for in-depth reading.



Clin Res Cardiol: 30 Aug 2019; 108:974-989
Doenst T, Bargenda S, Kirov H, Moschovas A, ... Diab M, Faerber G
Clin Res Cardiol: 30 Aug 2019; 108:974-989 | PMID: 30929035
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Impact:
Abstract

Single chamber implantable cardioverter defibrillator compared to dual chamber implantable cardioverter defibrillator: less is more! Data from the German Device Registry.

Bogossian H, Frommeyer G, Hochadel M, Ince H, ... Senges J, Lemke B
Background
In patients with high risk for sudden cardiac death the implantation of a defibrillator is an established treatment. However the benefits and risks for patients in accordance to the number of the leads are not clear. Even in the current guidelines a recommendation to this question is missing. We analyzed advantage and disadvantages of single-chamber implantable cardioverter defibrillators (VVI-ICD) versus dual-chamber implantable cardioverter defibrillators (DDD-ICD) in the prospective German Device Registry.
Methods
The data of 2240 patients who underwent ICD implantation in 45 German Centers between January 2007 and March 2011 were included in a prospective device registry (VVI: n = 1629, male = 1358, EF = 34% ± 13%; DDD: n = 611, male = 491, EF = 35% ± 14%).
Results
The in-hospital complications were significantly higher in the DDD-ICD group with higher revision/device complication rates (3.0% vs. 1.2%; p = 0.003) but also higher mortality rate (1.0% vs. 0.1%; p < 0.001). Regarding the adjusted data at 1-year follow-up DDD-ICD caused more device revisions, but no difference in rehospitalization and mortality.
Conclusion
It is still unclear whether DDD-ICD may be beneficial for patients with preserved sinus and atrioventricular nodal function. Our data show that the decision of the operator to choose a DDD-ICD in these patients must be taken very carefully. By choosing a DDD-ICD the patient is exposed to a significantly higher periprocedural complication rate and higher in-hospital mortality. In absence of relevant bradycardias implantation of a DDD-ICD is not justified.



Clin Res Cardiol: 09 Dec 2019; epub ahead of print
Bogossian H, Frommeyer G, Hochadel M, Ince H, ... Senges J, Lemke B
Clin Res Cardiol: 09 Dec 2019; epub ahead of print | PMID: 31823040
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Impact:
Abstract

Association between anemia and hematological indices with mortality among cardiac intensive care unit patients.

Rayes HA, Vallabhajosyula S, Barsness GW, Anavekar NS, ... Kashani KB, Jentzer JC
Background
Anemia and elevated red cell distribution width (RDW) or mean corpuscular volume (MCV) are associated with an adverse prognosis in patients with cardiovascular disease and critical illness. Limited data exist regarding these associations in unselected cardiac intensive care unit (CICU) patients.
Methods
Retrospective cohort study of CICU patients between January 1, 2007, and December 31, 2015, with a hemoglobin (Hb) level measured at admission. Multivariable regression was performed to determine predictors of hospital mortality, and Kaplan-Meier analysis was used to determine post-discharge survival.
Results
We included 9644 patients with a mean age of 67.5 ± 15.1 years, including 3604 (37.4%) females. The median (IQR) values of Hb, MCV and RDW were 12.2 g/dL (10.6, 13.7), 90.7 fL (87.3, 94.2) fL, and 14.1% (13.3, 15.8), respectively. Anemia (admission Hb < 12 g/dL) was present in 4434 (46%) patients. A total of 845 (8.8%) patients died in the hospital. Patients with anemia had higher hospital mortality (11.3% vs. 6.6%, unadjusted OR 1.82, 95% CI 1.58-2.10, p < 0.001). After multivariable regression, admission Hb and MCV were not significantly associated with hospital mortality (both p > 0.1), while admission RDW (adjusted OR 1.12 per 1%, 95% CI 1.07-1.18, p < 0.001) was significantly associated with hospital mortality. Hospital survivors with lower Hb, higher MCV, or higher RDW had lower post-discharge survival.
Conclusion
Elevated RDW on admission was independently associated with higher hospital mortality in CICU patients. These data emphasize the importance of hematologic abnormalities for mortality risk stratification in CICU populations.



Clin Res Cardiol: 17 Sep 2019; epub ahead of print
Rayes HA, Vallabhajosyula S, Barsness GW, Anavekar NS, ... Kashani KB, Jentzer JC
Clin Res Cardiol: 17 Sep 2019; epub ahead of print | PMID: 31535171
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Impact:
Abstract

The SAPPHIRE criteria, history of myocardial infarction and diabetes predict adverse outcomes following carotid endarterectomy similar to stenting.

Macharzina RR, Müller C, Vogt M, Messé SR, ... Neumann FJ, Zeller T
Aims
Identifying factors associated with worse outcome following carotid endarterectomy (CEA) is important to improve prevention of major adverse cardiovascular and cerebrovascular events (MACCE), yet rarely used for registries. We intended to identify predictors of MACCE following CEA as recently analysed for stenting.
Methods and results
Patients undergoing CEA at 2 centers over 13 years were entered into a database. Baseline clinical characteristics, procedural factors and a panel of clinical and lesion-related high-risk features (SHR) and exclusion criteria (SE), empirically compiled for stratification in the SAPPHIRE trial, were differentially analysed using Cox regressions. The analysis included 748 operations; 262 (35%) asymptomatic, 208 (28%) with previous strokes, and 278 (37%) with transient ischemic attacks (TIA). The overall 30-day MACCE rate was 6.7%, 5.0% in asymptomatic and 7.6% in symptomatic patients. Previous MI (HR 2.045, p = 0.022), diabetes (HR 2.111, p = 0.011) and symptomatic patients (HR 2.045, p = 0.044) were independently associated with MACCE. SE patients (n = 81) had a MACCE rate of 13.6%; the MACCE rate of the remainder dropped to 5.8% (4.7% in asymptomatic and 6.5% in symptomatic patients). Hazard ratio for SHR patients was 2.069 (CI 1.087-3.941) and 2.389 for SE (CI 1.223-4.666), each compared to all patients with lower risk and adjusted for symptomatic status. Among SHR and SE criteria NYHA 3-4, contralateral occlusions and intraluminal thrombus were significant determinants and MI < 4 weeks before CEA showed a strong trend (p = 0.05).
Conclusion
Patients identified by SHR and SE criteria, prior MI and diabetes warrant increased attention to prevent MACCE following CEA.



Clin Res Cardiol: 24 Sep 2019; epub ahead of print
Macharzina RR, Müller C, Vogt M, Messé SR, ... Neumann FJ, Zeller T
Clin Res Cardiol: 24 Sep 2019; epub ahead of print | PMID: 31555985
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Impact:
Abstract

Atrial inflammation in different atrial fibrillation subtypes and its relation with clinical risk factors.

Wu L, Emmens RW, van Wezenbeek J, Stooker W, ... Niessen HWM, Krijnen PAJ
Objective
Inflammation of the atria is an important factor in the pathogenesis of atrial fibrillation (AF). Whether the extent of atrial inflammation relates with clinical risk factors of AF, however, is largely unknown. This we have studied comparing patients with paroxysmal and long-standing persistent/permanent AF.
Methods
Left atrial tissue was obtained from 50 AF patients (paroxysmal = 20, long-standing persistent/permanent = 30) that underwent a left atrial ablation procedure either or not in combination with coronary artery bypass grafting and/or valve surgery. Herein, the numbers of CD45+ and CD3+ inflammatory cells were quantified and correlated with the AF risk factors age, gender, diabetes, and blood CRP levels.
Results
The numbers of CD45+ and CD3+ cells were significantly higher in the adipose tissue of the atria compared with the myocardium in all AF patients but did not differ between AF subtypes. The numbers of CD45+ and CD3+ cells did not relate significantly to gender or diabetes in any of the AF subtypes. However, the inflammatory infiltrates as well as CK-MB and CRP blood levels increased significantly with increasing age in long-standing persistent/permanent AF and a moderate positive correlation was found between the extent of atrial inflammation and the CRP blood levels in both AF subtypes.
Conclusion
The extent of left atrial inflammation in AF patients was not related to the AF risk factors, diabetes and gender, but was associated with increasing age in patients with long-standing persistent/permanent AF. This may be indicative for a role of inflammation in the progression to long-standing persistent/permanent AF with increasing age.



Clin Res Cardiol: 17 Feb 2020; epub ahead of print
Wu L, Emmens RW, van Wezenbeek J, Stooker W, ... Niessen HWM, Krijnen PAJ
Clin Res Cardiol: 17 Feb 2020; epub ahead of print | PMID: 32072262
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Impact:
Abstract

Implant-based multi-parameter telemonitoring of patients with heart failure and a defibrillator with vs. without cardiac resynchronization therapy option: a subanalysis of the IN-TIME trial.

Geller JC, Lewalter T, Bruun NE, Taborsky M, ... Hindricks G,
Aims
In the IN-TIME trial, automatic daily implant-based multiparameter telemonitoring significantly improved clinical outcomes in patients with chronic systolic heart failure and implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy defibrillator (CRT-D). We compared IN-TIME results for ICD and CRT-D subgroups.
Methods
Patients with LVEF ≤ 35%, NYHA class II/III, optimized drug treatment, no permanent atrial fibrillation, and a dual-chamber ICD (n = 274) or CRT-D (n = 390) were randomized 1:1 to telemonitoring or no telemonitoring for 12 months. Primary outcome measure was a composite clinical score, classified as worsened if the patient died or had heart failure-related hospitalization, worse NYHA class, or a worse self-reported overall condition.
Results
The prevalence of worsened score at study end was higher in CRT-D than ICD patients (26.4% vs. 18.2%; P = 0.014), as was mortality (7.4% vs. 4.1%; P = 0.069). With telemonitoring, odds ratios (OR) for worsened score and hazard ratios (HR) for mortality were similar in the ICD [OR = 0.55 (P = 0.058), HR = 0.39 (P = 0.17)] and CRT-D [OR = 0.68 (P = 0.10), HR = 0.35 (P = 0.018)] subgroups (insignificant interaction, P = 0.58-0.91).
Conclusion
Daily multiparameter telemonitoring has a potential to reduce clinical endpoints in patients with chronic systolic heart failure both in ICD and CRT-D subgroups. The absolute benefit seems to be higher in higher-risk populations with worse prognosis.



Clin Res Cardiol: 29 Sep 2019; 108:1117-1127
Geller JC, Lewalter T, Bruun NE, Taborsky M, ... Hindricks G,
Clin Res Cardiol: 29 Sep 2019; 108:1117-1127 | PMID: 30874886
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Impact:
Abstract

Impacts of non-recovery of trastuzumab-induced cardiomyopathy on clinical outcomes in patients with breast cancer.

Yoon HJ, Kim KH, Kim HY, Park H, ... Cho JG, Park JC
Objectives
The impacts of non-recovery of trastuzumab-induced left ventricular dysfunction (LVD) on clinical outcomes in breast cancer have been poorly studied. We investigated the predictors of LV-functional non-recovery and its impacts on clinical outcomes in breast cancer patients with trastuzumab-induced LVD.
Methods and results
A total of 243 patients with trastuzumab-induced LVD were divided into the recovered LVD group (n = 195) and non-recovered LVD group (n = 48). Major adverse clinical events (MACEs) including death, symptomatic heart failure (HF), and HF hospitalization (HHF) were compared. Hemoglobin and albumin levels were significantly lower in non-recovered LVD than in recovered LVD group. Non-recovered LVD group showed significantly larger LV end-diastolic and systolic dimension, higher pulmonary artery systolic pressure, lower LV ejection fraction (EF), and decreased global longitudinal strain than in recovered LVD group. Decreased LVEF, enlarged LV size, pulmonary hypertension, and anemia were independent predictors of LV-functional non-recovery. During 45.9 ± 23.5 months of follow-up, MACEs were developed in 32 patients: 15 deaths, 28 symptomatic HF, and 22 HHF. In Kaplan-Meier survival analysis, MACE free survival was significantly lower in non-recovered LVD group than in recovered LVD group (log rank p = 0.002).
Conclusion
LV-functional non-recovery was not uncommon in breast cancer patients with trastuzumab-induced cardiomyopathy, and non-recovered LVD was significantly associated with MACEs. Decreased LVEF, enlarged LV size, pulmonary hypertension, and anemia were independent predictors of LV-functional non-recovery. Careful monitoring for MACEs and intensive medical management should be considered in trastuzumab-induced cardiomyopathy with these characteristics.



Clin Res Cardiol: 30 Jul 2019; 108:892-900
Yoon HJ, Kim KH, Kim HY, Park H, ... Cho JG, Park JC
Clin Res Cardiol: 30 Jul 2019; 108:892-900 | PMID: 30737527
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Impact:
Abstract

Strain analysis reveals subtle systolic dysfunction in confirmed and suspected myocarditis with normal LVEF. A cardiac magnetic resonance study.

Porcari A, Merlo M, Crosera L, Stolfo D, ... Vitrella G, Sinagra G
Aims
Lake Louise Criteria (LLC) are time-dependent and some acute myocarditis (AM) with preserved left ventricular ejection fraction (LVEF) could be missed, due to the limited accessibility of Cardiac Magnetic Resonance (CMR). We aimed to assess the potential value of cardiac strain measured by feature tracking (FT) imaging in this population.
Methods and results
Eighty-three patients with clinically suspected AM and normal LVEF were divided into 39 \"confirmed AM\" (positive LLC) and 44 \"suspected AM\" (negative LLC). An age and gender-matched sample of 42 normal subjects underwent CMR. In all groups, FT-derived biventricular strains and STE- global longitudinal strain (GLS) were assessed, being regularly measurable. Strain values < 5th percentile of the control group were considered abnormal. \"Suspected\" and \"confirmed\" AM were similar, except for medium time of CMR evaluation (5.2 vs 1 months from presentation, respectively; p = 0.004). Compared to healthy controls, both \"suspected\" and \"confirmed\" AM showed significantly impaired strain values. LV-global circumferential strain (GCS), right ventricular GCS and LV-GLS were abnormal in 15.4% and 15.9%, 20.5% and 15.9%, 7.7% and 9.1% in \"confirmed\" and \"suspected\" AM, respectively. STE analysis confirmed the results on LV-GLS, however a weak correlation emerged between STE and CMR-FT LV-GLS (p = 0.08).
Conclusions
Compared to STE, CMR-FT analysis provided a more comprehensive and complementary biventricular strain evaluation that resulted similar in \"confirmed\" and \"suspected\" AM with normal LVEF. Conversely, mostly biventricular GCS was significantly reduced in up to 20% of patients, compared to healthy controls.



Clin Res Cardiol: 10 Dec 2019; epub ahead of print
Porcari A, Merlo M, Crosera L, Stolfo D, ... Vitrella G, Sinagra G
Clin Res Cardiol: 10 Dec 2019; epub ahead of print | PMID: 31828505
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Impact:
Abstract

Digitalis therapy is associated with higher comorbidities and poorer prognosis in patients undergoing ablation of atrial arrhythmias: data from the German Ablation Registry.

Frommeyer G, Brachmann J, Ince H, Spitzer SG, ... Senges J, Eckardt L
Background
Digitalis glycosides are employed for rate control of atrial fibrillation. Recent studies suggested potential harmful effects of digitalis monotherapy and combination with antiarrhythmic drugs. The aim of the present study was to assess the prevalence and potential impact of digitalis therapy on outcome in patients undergoing catheter ablation of supraventricular arrhythmias.
Methods and results
The German Ablation Registry is a nationwide, prospective registry with a 1-year follow-up investigating 12,566 patients receiving catheter ablations of supraventricular arrhythmias in 52 German centres. The present analysis focussed on pharmacotherapy in 8608 patients undergoing catheter ablation of atrial tachycardia, atrial fibrillation, or atrial flutter. Patients receiving digitalis therapy (n = 417) were older and presented a significantly increased prevalence of comorbidities including coronary artery disease, heart failure, diabetes, and pulmonary disease. One-year mortality was significantly higher in digitalis-treated patients (4.7% vs. 1.3%, p < 0.001), most strikingly in patients undergoing ablation of atrial flutter. This effect was maintained after adjustment for important risk factors. Similar results were obtained for as the combined endpoint of death, myocardial infarction, stroke and major bleeding (6.6% vs. 2.7%, p < 0.001), and non-fatal rehospitalisations (54.1% vs. 45.1%, p = 0.001).
Conclusion
In the present study of patients undergoing catheter ablation of supraventricular arrhythmias, an association of digitalis therapy with increased mortality and an increased rate of other severe adverse events were observed. The results from this \'real-life\' registry are consistent with previously published studies. However, whether digitalis therapy promotes a poorer prognosis or may just serve as a marker for this aspect cannot be thoroughly interpreted.



Clin Res Cardiol: 29 Sep 2019; 108:1083-1092
Frommeyer G, Brachmann J, Ince H, Spitzer SG, ... Senges J, Eckardt L
Clin Res Cardiol: 29 Sep 2019; 108:1083-1092 | PMID: 30798346
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Abstract

Uptake in antithrombotic treatment and its association with stroke incidence in atrial fibrillation: insights from a large German claims database.

Hohnloser SH, Basic E, Nabauer M
Background
Underuse of oral anticoagulation (OAC) for stroke prevention in atrial fibrillation (AF) results in thousands of preventable strokes in Germany each year. This study aimed to assess changes in antithrombotic therapy in AF patients after increased use of direct oral anticoagulants (DOACs) in Germany and to evaluate whether the adoption of DOAC therapy was associated with changes in AF-related stroke and bleeding over time.
Methods
Analyses were carried out on a large claims-based dataset of 4 million health-insured Germans. The study population consisted of 601,261 prevalent AF patients between 2011 and 2016 who were assigned to one of the following four treatment groups: DOAC, VKA, antiplatelets or no antithrombotic treatment. Treatment patterns were descriptively analysed and represented by cohort and CHADS-VASc score. Clinical outcomes before and after the adoption of DOAC therapy were assessed using Poisson regression models.
Results
Use of OAC increased from 42 to 61% between 2011 and 2016, mainly due to more frequent prescription of DOACs. However, some underuse of OAC therapy remained even in high risk AF patients. In parallel with the increased prescription rate of OAC, there was an overall 24% incidence reduction in stroke between 2011 and 2016 which was mainly driven by reductions in ischemic strokes. Over the same time period the risk for major bleeding remained unchanged.
Conclusion
Between 2011 and 2016, the use of guideline-conform antithrombotic therapy in Germany has significantly increased. This was associated with a significant decline in strokes without an increased incidence of bleeding complications.



Clin Res Cardiol: 30 Aug 2019; 108:1042-1052
Hohnloser SH, Basic E, Nabauer M
Clin Res Cardiol: 30 Aug 2019; 108:1042-1052 | PMID: 30771066
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Abstract

Doxorubicin treatments induce significant changes on the cardiac autonomic nervous system in childhood acute lymphoblastic leukemia long-term survivors.

Caru M, Corbin D, Périé D, Lemay V, ... Sinnett D, Curnier D
Aims
Acute lymphoblastic leukemia (ALL) is one of the leading malignancies in children worldwide. The cardiotoxicity of anti-cancer treatments leads to a dysfunction of the cardiac autonomic nervous system. Protection strategies, with dexrazoxane treatments, were used to counter these adverse effects. The aim of this study was to investigate the effects of the treatments on the cardiac autonomic nervous system.
Methods and results
A total of 203 cALL survivors were included in our analyses and were classified into 3 categories based on the prognostic risk group: standard risk, high risk with and without dexrazoxane. A 24-h Holter monitoring was performed to study the cardiac autonomic nervous system. The frequency domain heart rate variability (HRV) was used to validate the cardiac autonomic nervous system modifications. Other analyses were performed using linear HRV indexes in the time domain and non-linear indexes. A frequency domain HRV parameters analysis revealed significant differences on an overall time-period of 24 h. A repeated measures ANOVA indicated a group-effect for the low frequency (p = 0.029), high frequency (p = 0.03) and LF/HF ratio (p = 0.029). Significant differences in the time domain and in the non-linear power spectral density HRV parameters were also observed.
Conclusion
Anti-cancer treatments induced significant changes in the cardiac autonomic nervous system. The HRV was sensitive enough to detect cardiac autonomic nervous system alterations depending on the cALL risk category. Protection strategies (i.e., dexrazoxane treatments), which were used to counter the adverse effects of doxorubicin, could prevent changes observed in the cardiac autonomic nervous system.



Clin Res Cardiol: 30 Aug 2019; 108:1000-1008
Caru M, Corbin D, Périé D, Lemay V, ... Sinnett D, Curnier D
Clin Res Cardiol: 30 Aug 2019; 108:1000-1008 | PMID: 30778669
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This program is still in alpha version.