Publications by authors named "Ibrahim Akin"

484 Publications

Sex differences and adherence of patients treated with wearable cardioverter-defibrillator: insights from an international multicenter register.

J Cardiovasc Electrophysiol 2022 Aug 5. Epub 2022 Aug 5.

Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Germany.

Aims: Treatment with the wearable cardioverter defibrillator (WCD) may protect against sudden cardiac death (SCD) as a bridging therapy until a cardioverter-defibrillator may be implanted. We analyzed in a multicenter setting a consecutive patient cohort wearing WCD to explore sex differences.

Methods And Results: We analyzed 708 consecutive patients, 579 (81.8%) from whom were males and 129 (18.2%) females (age, 60.5±14 vs. 61.6±17 years old; p=0.44). While the rate of ischemic cardiomyopathy (ICM) as a cause of prescription of WCD was significantly higher in males as compared to females (42.7% vs. 26.4%; p=0.001), females received it more frequently due to non-ischemic cardiomyopathy (NICM) (55.8% vs. 42.7%); p=0.009). The wear time of WCD was equivalent in both groups (21.1±4.3 hours/days in males vs. 21.5±4.4 hours/days in females; p=0.27; and 62.6±44.3 days in males vs. 56.5±39 days in females; p=0.15). Mortality was comparable in both groups at 2-year-follow-up (6.8% in males vs. 9.7% in females; p=0.55). Appropriate WCD shocks and the incidence of ICD implantations were similar in both groups (2.4% in males vs. 3.9% in females; p=0.07) (35.1% in males vs. 31.8% in females; p=0.37), respectively. In age tertile analysis, compliance was observed more in 73-91 years old group as compared to 14-51 years old group (87.8% vs. 68.3%; p<0.001).

Conclusion: Compliance for wearing WCD was excellent regardless of sex. Furthermore, mortality and the incidence of ICD implantations were comparable in both sexes. Appropriate WCD shocks were similar in both sexes. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/jce.15648DOI Listing
August 2022

Epigenetic mechanism of L-type calcium channel β-subunit downregulation in short QT human induced pluripotent stem cell-derived cardiomyocytes with CACNB2 mutation.

Europace 2022 Jul 27. Epub 2022 Jul 27.

First Department of Medicine (Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care), Medical Faculty Mannheim, University Medical Centre Mannheim (UMM), University of Heidelberg, Theodor-Kutzer-Ufer 1-3, Mannheim 68167, Germany.

Aims: A loss-of-function mutation in L-type calcium (Ca2+) channel subunit gene CACNB2 has been reported to cause short QT syndrome subtype 5 (SQT5). However, the mechanism underlying the loss-of-function of the Ca2+ channel has not been clarified. In the present study, we aim to explore the DNA methylation mechanism of L-type Ca2+ channel downregulation in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) of SQT5.

Methods And Results: The hiPSC-CMs were generated from a healthy donor and a SQT5 patient carrying the CACNB2 variant c.1439C > T/p.S480L. The variant was genetically corrected using ribonucleoprotein-based CRISPR/Cas9 technique to obtain an isogenic control cell line. The action potential (AP) and Ca2+ current were measured by patch clamp. Protein expression levels were determined by western blotting. Dot blotting and bisulfite sequence were performed for epigenetic study. Our results showed that AP durations at 10% repolarization (APD10) and 50% repolarization (APD50) were significantly shortened in SQT5 cells and both the expression level of the β-subunit and channel current of L-type Ca2+ channel were reduced. Besides, an increased level of whole-genome DNA methylation and DNA methylation of CpG island in the promoter region of CACNB2 gene was detected. Overexpression of demethylation enzyme could rescue the decreased expression of CACNB2 and the L-type Ca2+ current.

Conclusion: In SQT5 hiPSC-CMs carrying the CACNB2-S480L variant, the decreased L-type Ca2+ current resulting from decreased CACNB2 protein expression was caused by enhanced methylation in the promoter region of the CACNB2 gene and upregulation of DNA methyltransferases might be one of the mechanisms.
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http://dx.doi.org/10.1093/europace/euac091DOI Listing
July 2022

Serial Changes in Coronary Plaque Formation Using CT Angiography in Patients Undergoing PCSK9-Inhibitor Therapy With 1-year Follow-up.

J Thorac Imaging 2022 Jul 8. Epub 2022 Jul 8.

First Department of Medicine-Cardiology, University Medical Centre Mannheim, DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim.

Purpose: Previous studies have shown positive effects of intensive low-density lipoprotein (LDL)-lowering therapy on atheroma volume using invasive intravascular ultrasound. This study describes the changes in coronary plaque composition on coronary computed tomography angiography in patients treated with proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors.

Materials And Methods: In this prospective study, coronary plaques were analyzed using third-generation dual-source computed tomography before and after 1 year of PCSK9-inhibitor treatment. Plaque markers included total plaque volume (TPV), calcified plaque volume (CPV), noncalcified plaque volume (NCPV), lumen volume and vessel volume (VV), minimal luminal area (MLA), minimal lumen diameter (MLD), corrected coronary opacification, eccentricity, remodeling index, and functional plaque parameters. Primary endpoint was defined as change in TPV; the secondary endpoint was TPV or CPV regression or nominal change in plaque parameters.

Results: We analyzed 74 coronary plaques in 23 patients (60±9 y, 65% male). After 1 year of PCSK9-inhibitor treatment, LDL was reduced from 148 to 66 mg/dL (P<0.0001). Significant changes were found for VV (196 to 215 mm3, P=0.0340), MLA (3.1 to 2.6 mm2, P=0.0413), and MLD (1.7 to 1.4 mm, P=0.0048). TPV, CPV, NCPV, lumen volume, and functional plaque parameters did not change significantly (P>0.05).

Conclusions: Coronary artery plaque analysis by coronary computed tomography angiography highlights that LDL lowering therapy affects plaque composition. The primary endpoint of TPV change was not reached; however, VV, MLA, and MLD changed significantly.
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http://dx.doi.org/10.1097/RTI.0000000000000666DOI Listing
July 2022

Digitalis therapy in patients with ventricular tachyarrhythmias.

Scand Cardiovasc J 2022 12;56(1):198-207

First Department of Medicine, Faculty of Medicine Mannheim, University Medical Centre Mannheim (UMM), University of Heidelberg, Mannheim, Germany.

. The study sought to assess the prognostic value of treatment with digitalis on long-term prognosis in patients with ventricular tachyarrhythmias and atrial fibrillation (AF) and/or heart failure (HF). . Data regarding the outcome of digitalis therapy following ventricular tachyarrhythmias is limited. A large retrospective registry was used including consecutive patients with episodes of ventricular tachycardia (VT) or fibrillation (VF) from 2002 to 2015. Patients treated with digitalis were compared to patients without. The primary prognostic endpoint was all-cause mortality at 3 years, secondary endpoints comprised a composite arrhythmic endpoint (i.e. recurrences of ventricular tachyarrhythmias, appropriate implantable cardioverter defibrillator (ICD) therapies, sudden cardiac death) and cardiac rehospitalization. Kaplan Mayer survival curves, multivariable cox regression, and time trend analyses were applied for statistics. Eight hundred and thirty-one patients were included (20% treated with digitalis and 80% without). At 3 years, digitalis treatment was not associated with all-cause mortality following ventricular tachyarrhythmias (24 21%, log-rank  = .736; HR = 1.063; 95% CI 0.746-1.515;  = .736). However, digitalis therapy was associated with an increased risk of the composite arrhythmic endpoint (38 23%; log-rank  = .001; HR = 1.719; 95% CI 1.279-2.311;  = .001) and cardiac rehospitalization (31 18%; log-rank  = .001; HR = 1.829; 95% CI 1.318-2.538;  = .001), which was still evident within multivariable Cox regression analyses. Finally, digitoxin may be associated with a worse prognosis than digoxin. Digitalis therapy was not associated with mortality in patients with ventricular tachyarrhythmias, but with increased risk of the composite arrhythmic endpoint and cardiac rehospitalization at 3 years.
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http://dx.doi.org/10.1080/14017431.2022.2091793DOI Listing
December 2022

Ticagrelor or prasugrel in patients with acute coronary syndrome with off-hour versus on-hour presentation: a subgroup analysis of the ISAR-REACT 5 trial.

Clin Res Cardiol 2022 Jul 5. Epub 2022 Jul 5.

First Department of Medicine, Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany.

Objectives: To assess the efficacy and safety of ticagrelor versus prasugrel in patients with acute coronary syndrome (ACS) presenting during off- and on-hours.

Background: The efficacy and safety of ticagrelor versus prasugrel in patients with ACS according to time of hospital presentation remain unknown.

Methods: This post hoc analysis of the ISAR-REACT 5 trial included 1565 patients with ACS presenting off-hours and 2453 patients presenting on-hours, randomized to ticagrelor or prasugrel. The primary endpoint was a composite of death, myocardial infarction, or stroke; the safety endpoint was Bleeding Academic Research Consortium (BARC) type 3-5 bleeding, both at 12 months.

Results: The primary endpoint occurred in 80 patients (10.4%) in the ticagrelor group and 57 patients (7.3%) in the prasugrel group in patients presenting off-hours (hazard ratio [HR] = 1.45; 95% confidence interval [CI] 1.03-2.03; P = 0.033), and 104 patients (8.5%) in the ticagrelor group and 80 patients (6.7%) in the prasugrel group in patients presenting on-hours (HR = 1.29 [0.97-1.73]; P = 0.085), without significant treatment arm-by-presentation time interaction (P = 0.62). BARC type 3 to 5 bleeding occurred in 35 patients (5.1%) in the ticagrelor group and 37 patients (5.3%) in the prasugrel group (P = 0.84) in patients presenting off-hours, and 60 patients (5.9%) in the ticagrelor group and 43 patients (4.6%) in the prasugrel group in patients presenting on-hours (P = 0.17).

Conclusions: In patients with ACS planned to undergo an invasive treatment strategy, time of presentation (off-hours vs. on-hours) does not interact significantly with the relative efficacy and safety of ticagrelor vs. prasugrel.

Clinical Trial Registration: NCT01944800.
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http://dx.doi.org/10.1007/s00392-022-02040-zDOI Listing
July 2022

The art of selection in coronary bypass grafting.

Eur Heart J 2022 Jul 5. Epub 2022 Jul 5.

First Department of Medicine, University of Heidelberg Medical Centre, Mannheim, Germany.

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http://dx.doi.org/10.1093/eurheartj/ehac351DOI Listing
July 2022

Happy Heart Syndrome: Frequency, Characteristics, and Outcome of Takotsubo Syndrome Triggered by Positive Life Events.

JACC Heart Fail 2022 Jul 4;10(7):459-466. Epub 2022 May 4.

Medical Clinic II, University Heart Center Lübeck, Lübeck, Germany; German Center for Cardiovascular Research, Partner Site Hamburg-Kiel-Lübeck, Lübeck, Germany.

Background: The association with a preceding stressor is a characteristic feature of takotsubo syndrome (TTS). Negative emotions before TTS are common and led to the popular term "broken heart syndrome." In contrast, pleasant triggers ("happy heart syndrome") are rare and are scarcely investigated.

Objectives: The authors analyzed the frequency, clinical characteristics, and prognostic implications of positive emotional stressors in the multicenter GEIST (GErman-Italian-Spanish Takotsubo) Registry.

Methods: Patients enrolled in the registry were categorized according to their stressors. This analysis compared patients with pleasant emotional events with patients with negative emotional events.

Results: Of 2,482 patients in the registry, 910 patients (36.7%) exhibited an emotional trigger consisting of 873 "broken hearts" (95.9%) and 37 "happy hearts" (4.1%). Consequently, the prevalence of pleasant emotional triggers was 1.5% of all TTS cases. Compared with patients with TTS with negative preceding events, patients with happy heart syndrome were more frequently male (18.9% vs 5.0%; P < 0.01) and had a higher prevalence of atypical ballooning patterns (27.0% vs 12.5%; P = 0.01), particularly midventricular ballooning. In-hospital complications, including death, pulmonary edema, cardiogenic shock, or stroke (8.1% vs 12.3%; P = 0.45), and long-term mortality rates (2.7% vs 8.8%; P = 0.20) were similar in "happy hearts" and "broken hearts."

Conclusions: Happy heart syndrome is a rare type of TTS characterized by a higher prevalence of male patients and atypical, nonapical ballooning compared with patients with negative emotional stressors. Despite similar short- and long-term outcomes in our study, additional data are needed to explore whether numerically lower event rates in "happy hearts" would be statistically significant in a larger sample size. (GErman-Italian-Spanish Takotsubo Registry [GEIST Registry]; NCT04361994).
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http://dx.doi.org/10.1016/j.jchf.2022.02.015DOI Listing
July 2022

Diagnostic value of sST2, VCAM-1 and adiponectin in patients with breast cancer to predict anti-tumor treatment-related cardiac events: A pilot study.

Oncol Res Treat 2022 Jun 28. Epub 2022 Jun 28.

Aim The present exploratory study investigated the diagnostic value of inflammatory markers in patients with breast cancer to predict anti-tumour treatment-related cardiac events. Methods Twenty-one patients with breast cancer were enrolled in this prospective observational study and followed over 6 months. Transthoracic echocardiography and measurement of cardiac (N terminal prohormone of brain natriuretic peptide (NT proBNP), Troponin I (TnI)) and inflammatory biomarkers (vascular adhesion molecule 1 (VCAM-1), soluble suppression of tumorigenesis-2 (sST2), adiponectin) was performed at 3-month intervals (baseline, follow-up, final visit). Cardiac events were defined as decrease in left ventricular ejection fraction (LVEF, decrease by 10 % or < 50 %) or increase in global longitudinal strain (GLS, increase by 15 % or > 16 %), as a more sensitive marker of LV function. Results Cardiac deterioration was observed in nine out of 21 patients (event group). While LVEF did not differ significantly between the two groups (event vs no event) at any visit, GLS was significantly higher during follow-up (follow-up: event -16 ± 3.3 % vs no event -18 ± 1.6 %, p = 0.04, final visit: event -16 ± 2.1 % vs no event -19 ± 1.9 %, p = 0.003). NT-proBNP was numerically higher in patients with a cardiac event during all visits, with NT-proBNP negatively correlated with LVEF and MAPSE (both r = -0.33, p = 0.02), whereas GLS (r = 0.40, p = 0.006), TnI (r = 0.44, p = 0.001), and VCAM-1 (r = 0.48, p = 0.003) showed a positive association with NT-proBNP. In comparison, higher VCAM 1 and sST2 concentrations were detected in the event group at both baseline and the final visit, with a significant difference for baseline (VCAM-1: p = 0.02; sST2: p = 0.03). Adiponectin was also lower in patients with a treatment-related event. Thresholds for VCAM 1 > 762 ng/ml and sST2 > 18.7 ng/ml, as detected by ROC analysis, correlated best with the primary endpoint. Conclusion Cardiac events during anti-tumour treatment in patients with breast cancer are relatively common. Inflammatory markers such as VCAM-1 or sST2 were associated with an increased likelihood for occurrence of a treatment-related event, which may therefore hold the promise to better identify patients at high risk.
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http://dx.doi.org/10.1159/000525683DOI Listing
June 2022

Kidney Failure among Patients with Takotsubo Syndrome or Myocardial Infarction: A Retrospective Analysis.

J Cardiovasc Dev Dis 2022 Jun 9;9(6). Epub 2022 Jun 9.

First Department of Medicine Cardiology, University Medical Centre Mannheim (UMM), Faculty of Medicine Mannheim, University of Heidelberg, DZHK (German Center for Cardiovascular Research) Partner Site Mannheim, 68167 Mannheim, Germany.

Takotsubo syndrome (TTS) is a syndrome with ambiguous pathophysiology. Impaired kidney function (KF) seems to impact the outcome of patients with TTS. We hypothesized that KF worsens the outcome among TTS patients and furthermore, TTS patients with concomitant KF experience more adverse events compared to myocardial infarction (MI) patients with concomitant KF. This retrospective single-center study comprised two groups (cohorts) of patients including patients with TTS and concomitant KF ( = 61, 27.1%) and patients with MI and concomitant KF ( = 164, 72.9%). The clinical outcomes were delineated as short-term outcomes defined as in-hospital adverse events during index hospitalization and long-term outcomes defined as adverse events over five-year clinical follow-ups. All-cause mortality, stroke, cardiopulmonary resuscitation (CPR), life-threatening arrhythmias, need for respiratory support, and cardiogenic shock with subsequent use of inotropic agents during index hospitalization were denoted as in-hospital adverse events. All-cause mortality, rehospitalization due to heart failure, stroke, thromboembolic events, and the recurrence of primary pathology (TTS and MI) were analyzed during five-year follow-ups after index hospitalization. A higher mortality rate was noted among TTS patients with KF compared to TTS without KF. In addition, in-hospital event rates in patients with TTS and concomitant KF compared to MI and concomitant KF were comparable with the exception of a higher rate of respiratory support in TTS patients. The mortality rate was significantly higher among patients with TTS and KF at 4 years (29.5% vs. 15.9%, = 0.02) and 5 years (34.4% vs. 20.7%, = 0.03) in comparison to patients with MI and concomitant KF. In contrast, the rate of re-hospitalization related to heart failure was higher at 30 days, and at one-, four-, and five-year follow-ups in patients suffering from MI and KF compared to TTS and concomitant KF. Additionally, the recurrence of MI after 4 and 5 years was higher than the recurrence of TTS (4.9% vs. 15.2%; 4.9% vs. 16.5%). There were no differences in life-threatening arrhythmias and stroke in both groups. Patients with TTS and concomitant KF have higher all-cause mortality when compared to MI and concomitant KF. The mechanisms responsible remain to be determined.
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http://dx.doi.org/10.3390/jcdd9060186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9224747PMC
June 2022

Effect of light intensity on the tear production, central corneal thickness, and intraocular pressure in broiler chickens.

Vet Ophthalmol 2022 Jun 17. Epub 2022 Jun 17.

Department of Surgery, Faculty of Veterinary Medicine, Aydin Adnan Menderes University, Aydin, Turkey.

Objective: The objective of the present study was to examine the effect of different light intensities on tear production, corneal thickness, and intraocular pressure in broilers.

Animals Studied: Both eyes of 72 male broilers were evaluated in this study.

Materials And Methods: Broilers were divided into the following three groups: low light intensity (n = 24, 5 lux), moderate light intensity (n = 24, 20 lux), and high light intensity (n = 24, 80 lux). The eyes of all birds (n = 72) underwent a complete ophthalmic examination, which included the Schirmer tear test (STT-I), intraocular pressure (IOP), and the central cornea thickness measurement (CCT). The effect of light intensity on the Schirmer test, intraocular pressure, and central corneal thickness values was examined at eye and animal level (right and left eyes separately and cumulatively/no distinguishing left or right) by using one-way ANOVA.

Results: At the animal level, without discrimination of left and right eye measurements, statistically significant differences were found between 5-20 and 20-80 lux groups on IOP measurements (p < .05). The difference in CCT measurements between the 5 and 20 lux groups was statistically significant (p < .05), and the corneal thickness of the 5 lux group animals was found to be statistically significant and higher than the 20 lux group (p < .05).

Conclusions: In conclusion, light intensity has an influence on eye health in broilers. Present results may attribute to the future studies as a reference value for broilers raised under different light intensities.
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http://dx.doi.org/10.1111/vop.13005DOI Listing
June 2022

Development and validation of a decision support tool for the diagnosis of acute heart failure: systematic review, meta-analysis, and modelling study.

BMJ 2022 06 13;377:e068424. Epub 2022 Jun 13.

First Department of Medicine, University Medical Centre Mannheim, Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany.

Objectives: To evaluate the diagnostic performance of N-terminal pro-B-type natriuretic peptide (NT-proBNP) thresholds for acute heart failure and to develop and validate a decision support tool that combines NT-proBNP concentrations with clinical characteristics.

Design: Individual patient level data meta-analysis and modelling study.

Setting: Fourteen studies from 13 countries, including randomised controlled trials and prospective observational studies.

Participants: Individual patient level data for 10 369 patients with suspected acute heart failure were pooled for the meta-analysis to evaluate NT-proBNP thresholds. A decision support tool (Collaboration for the Diagnosis and Evaluation of Heart Failure (CoDE-HF)) that combines NT-proBNP with clinical variables to report the probability of acute heart failure for an individual patient was developed and validated.

Main Outcome Measure: Adjudicated diagnosis of acute heart failure.

Results: Overall, 43.9% (4549/10 369) of patients had an adjudicated diagnosis of acute heart failure (73.3% (2286/3119) and 29.0% (1802/6208) in those with and without previous heart failure, respectively). The negative predictive value of the guideline recommended rule-out threshold of 300 pg/mL was 94.6% (95% confidence interval 91.9% to 96.4%); despite use of age specific rule-in thresholds, the positive predictive value varied at 61.0% (55.3% to 66.4%), 73.5% (62.3% to 82.3%), and 80.2% (70.9% to 87.1%), in patients aged <50 years, 50-75 years, and >75 years, respectively. Performance varied in most subgroups, particularly patients with obesity, renal impairment, or previous heart failure. CoDE-HF was well calibrated, with excellent discrimination in patients with and without previous heart failure (area under the receiver operator curve 0.846 (0.830 to 0.862) and 0.925 (0.919 to 0.932) and Brier scores of 0.130 and 0.099, respectively). In patients without previous heart failure, the diagnostic performance was consistent across all subgroups, with 40.3% (2502/6208) identified at low probability (negative predictive value of 98.6%, 97.8% to 99.1%) and 28.0% (1737/6208) at high probability (positive predictive value of 75.0%, 65.7% to 82.5%) of having acute heart failure.

Conclusions: In an international, collaborative evaluation of the diagnostic performance of NT-proBNP, guideline recommended thresholds to diagnose acute heart failure varied substantially in important patient subgroups. The CoDE-HF decision support tool incorporating NT-proBNP as a continuous measure and other clinical variables provides a more consistent, accurate, and individualised approach.

Study Registration: PROSPERO CRD42019159407.
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http://dx.doi.org/10.1136/bmj-2021-068424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9189738PMC
June 2022

Fever following Covid-19 vaccination in subjects with Brugada syndrome: Incidence and management.

J Cardiovasc Electrophysiol 2022 Jun 13. Epub 2022 Jun 13.

Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.

Background: Fever is a potential side effect of the Covid-19 vaccination. Patients with Brugada syndrome (BrS) have an increased risk of life-threatening arrhythmias when experiencing fever. Prompt treatment with antipyretic drugs is suggested in these patients.

Aim Of The Study: To evaluate the incidence and management of fever within 48 h from Covid-19 vaccination among BrS patients.

Methods: One hundred sixty-three consecutive patients were enrolled in a prospective registry involving five European hospitals with a dedicated inherited disease ambulatory.

Results: The mean age was 50 ± 14 years and 121 (75%) patients were male. Prevalence of Brugada electrocardiogram (ECG) pattern type-1, -2, and -3 was 32%, 44%, and 24%, respectively. Twenty-eight (17%) patients had an implantable cardioverter-defibrillator (ICD). Fever occurred in 32 (19%) BrS patients after 16 ± 10 h from vaccination, with a peak of body temperature of 37.9° ± 0.5°. Patients with fever were younger (39 ± 13 vs. 48 ± 13 years, p = .04). No additional differences in terms of sex and cardiovascular risk factors were found between patients with fever and not. Twenty-seven (84%) out of 32 patients experienced mild fever and five (16%) moderate fever. Pharmacological treatment with antipyretic drugs was required in 18 (56%) out of 32 patients and was associated with the resolution of symptoms. No patient required hospital admission and no arrhythmic episode was recorded in patients with ICD within 48 h after vaccination. No induced type 1 BrS ECG pattern and new ECG features were found among patients with moderate fever.

Conclusion: Fever is a common side effect in BrS patients after the Covid-19 vaccination. Careful evaluation of body temperature and prompt treatment with antipyretic drugs may be needed.
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http://dx.doi.org/10.1111/jce.15596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9350146PMC
June 2022

Special Issue: Sudden Cardiac Death: Clinical Updates and Perspectives.

J Clin Med 2022 May 31;11(11). Epub 2022 May 31.

First Department of Medicine, University Medical Centre Mannheim (UMM), Faculty of Medicine Mannheim, University of Heidelberg, 68167 Mannheim, Germany.

Sudden cardiac death (SCD) is defined as unexpected sudden death due to cardiac causes, occurring within one hour after the onset of symptoms [...].
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http://dx.doi.org/10.3390/jcm11113120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9181130PMC
May 2022

Prognostic Value of Cardiac Troponin I in Patients with Ventricular Tachyarrhythmias.

J Clin Med 2022 May 25;11(11). Epub 2022 May 25.

First Department of Medicine, University Medical Centre Mannheim (UMM), Faculty of Medicine Mannheim, University of Heidelberg, 68167 Mannheim, Germany.

Besides the diagnostic role in acute myocardial infarction, cardiac troponin I levels (cTNI) may be increased in various other clinical conditions, including heart failure, valvular heart disease and sepsis. However, limited data are available regarding the prognostic role of cTNI in the setting of ventricular tachyarrhythmias. Therefore, the present study sought to assess the prognostic impact of cTNI in patients with ventricular tachyarrhythmias (i.e., ventricular tachycardia (VT) and fibrillation (VF)) on admission. A large retrospective registry was used, including all consecutive patients presenting with ventricular tachyarrhythmias from 2002 to 2015. The prognostic impact of elevated cTNI levels was investigated for 30-day all-cause mortality (i.e., primary endpoint) using Kaplan-Meier, receiver operating characteristic (ROC), multivariable Cox regression analyses and propensity score matching. From a total of 1104 patients with ventricular tachyarrhythmias and available cTNI levels on admission, 46% were admitted with VT and 54% with VF. At 30 days, high cTNI was associated with the primary endpoint (40% vs. 22%; log rank = 0.001; HR = 2.004; 95% CI 1.603-2.505; = 0.001), which was still evident after multivariable adjustment and propensity score matching (30% vs. 18%; log rank = 0.003; HR = 1.729; 95% CI 1.184-2.525; = 0.005). Significant discrimination of the primary endpoint was especially evident in VT patients (area under the curve (AUC) 0.734; 95% CI 0.645-0.823; = 0.001). In contrast, secondary endpoints, including all-cause mortality at 30 months and a composite arrhythmic endpoint, were not affected by cTNI levels. The risk of cardiac rehospitalization was lower in patients with high cTNI, which was no longer observed after propensity score matching. In conclusion, high cTNI levels were associated with increased risk of all-cause mortality at 30 days in patients presenting with ventricular tachyarrhythmias.
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http://dx.doi.org/10.3390/jcm11112987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9181556PMC
May 2022

Adverse Cardiovascular Effects of Anti-tumor Therapies in Patients With Breast Cancer: A Single-center Cross-sectional Analysis.

Anticancer Res 2022 Jun;42(6):3075-3084

Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany;

Background/aim: Cardiotoxicity due to antitumor therapy is a dreaded complication and could thus impact the prognosis of patients with breast cancer. This study sought to analyze the occurrence of adverse cardiovascular events and to identify potential risk factors.

Patients And Methods: A total of 136 patients with breast cancer were divided into two groups based on the occurrence of treatment-related cardiovascular toxicity [event 47 (35%) vs. no event 89 (65%)]. Patients were followed over a median of 45 months (range=37-83 months).

Results: Most common events were thromboembolic complications (26%), followed by heart failure (15%) and acute toxic cardiomyopathy (5%), with a reduced left ventricular ejection fraction [LVEF (%), no event 59±5.0 vs. event 55±11, p=0.01 ]. Patients with leftsided breast cancer and an advanced stage disease had a higher risk of developing adverse cardiovascular events. The highest risk was found for patients with a high number of cardiovascular risk factors. In addition to LVEF, mitral annular plane systolic excursion was also significantly reduced in the event group, while there was a trend for higher global longitudinal strain. During follow-up, 26 patients (19.1%) deceased, whereof 12 had a treatment-related cardiovascular event, but without statistical difference.

Conclusion: Treatment-related cardiovascular events are relatively common in about one third of patients with breast cancer. Women with a cardiovascular risk profile or an advanced stage disease had a higher risk for adverse events. Despite the treatment-related cardiac deterioration, no difference in mortality was observed during follow up.
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http://dx.doi.org/10.21873/anticanres.15795DOI Listing
June 2022

Gender Differences in Takotsubo Syndrome.

J Am Coll Cardiol 2022 05;79(21):2085-2093

University of Foggia, Department of Medical and Surgical Sciences, Foggia, Italy.

Background: Male sex in takotsubo syndrome (TTS) has a low incidence and it is still not well characterized.

Objectives: The aim of the present study is to describe TTS sex differences.

Methods: TTS patients enrolled in the international multicenter GEIST (GErman Italian Spanish Takotsubo) registry were analyzed. Comparisons between sexes were performed within the overall cohort and using an adjusted analysis with 1:1 propensity score matching for age, comorbidities, and kind of trigger.

Results: In total, 286 (11%) of 2,492 TTS patients were men. Male patients were younger (age 69 ± 13 years vs 71 ± 11 years; P = 0.005), with higher prevalence of comorbid conditions (diabetes mellitus 25% vs 19%; P = 0.01; pulmonary diseases 21% vs 15%; P = 0.006; malignancies 25% vs 13%; P < 0.001) and physical trigger (55 vs 32% P < 0.01). Propensity-score matching yielded 207 patients from each group. After 1:1 propensity matching, male patients had higher rates of cardiogenic shock and in-hospital mortality (16% vs 6% and 8% vs 3%, respectively; both P < 0.05). Long-term mortality rate was 4.3% per patient-year (men 10%, women 3.8%). Survival analysis showed higher mortality rate in men during the acute phase in both cohorts (overall: P < 0.001; matched: P = 0.001); mortality rate after 60 days was higher in men in the overall (P = 0.002) but not in the matched cohort (P = 0.541). Within the overall population, male sex remained independently associated with both in-hospital (OR: 2.26; 95% CI: 1.16-4.40) and long-term mortality (HR: 1.83; 95% CI: 1.32-2.52).

Conclusions: Male TTS is featured by a distinct high-risk phenotype requiring close in-hospital monitoring and long-term follow-up.
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http://dx.doi.org/10.1016/j.jacc.2022.03.366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8972425PMC
May 2022

Pooled Analysis of Complications with Transvenous ICD Compared to Subcutaneous ICD in Patients with Catecholaminergic Polymorphic Ventricular Arrhythmia.

J Pers Med 2022 Mar 28;12(4). Epub 2022 Mar 28.

Bergmannsheil Bochum, Medical Clinic II, Department of Cardiology and Angiology, Ruhr University, 44789 Bochum, Germany.

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is associated with arrhythmic events which may lead to sudden cardiac death (SCD). A leading therapy for CPVT besides medical treatment with beta-blockers is the use of an implantable cardioverter-defibrillator (ICD). For this paper we compared data from a pooled analysis to get further evidence about the complications of transvenous and subcutaneous ICDs.

Methods: We gathered data from a search of PubMed, Web of Science, Cochrane Library and Cinahl. For our analysis, we chose 30 studies with a total number of 784 patients. We compared the data regarding complications caused by different ICD device types.

Results: During a mean follow up of 38.9 months for the patients with ICD implantation ( = 337), data showed a complication rate of 101 (30%). A total of 330 (98%) of them received a transvenous-ICD (T-ICD) and 7 (2%) a subcutaneous-ICD (S-ICD). A total of 97 (29.4%) of the T-ICD patients and 4 (57.1%) of the S-ICD patients had at least one complication. Of the 234 complications that occurred in T-ICD patients 152 (65%) were inappropriate shocks due to supraventricular arrhythmias, T/R-wave oversensing or electrode defect, 26 (11.1%) lead fracture/failure, 1 (0.4%) electrode defect, 46 were (19.7%) events of electrical storms, 1 (0.4%) thromboembolic event, 2 (0.8%) cases of endocarditis and 6 (2.6%) infections of the ICD-pocket. Ten (100%) of the complications for the four patients with the S-ICD were an event of an inappropriate shock due to supraventricular arrhythmias, T/R-wave oversensing or electrode defect.

Conclusion: Subcutaneous ICDs (S-ICD) show a certain advantage over T-ICDs regarding lead-related complications. Nevertheless, they still show problems with inappropriate shocks and other ICD related complications. Therefore, a case-by-case decision is advised, but the continuous improvement of S-ICD might make it an overall advantageous therapy option in the future.
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http://dx.doi.org/10.3390/jpm12040536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9029805PMC
March 2022

Lipopolysaccharide Modifies Sodium Current Kinetics through ROS and PKC Signalling in Induced Pluripotent Stem-Derived Cardiomyocytes from Brugada Syndrome Patient.

J Cardiovasc Dev Dis 2022 Apr 15;9(4). Epub 2022 Apr 15.

Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim (UMM), Heidelberg University, 68167 Mannheim, Germany.

Studies have suggested a connection between inflammation and arrhythmogenesis of Brugada syndrome (BrS). However, experimental studies regarding the roles of inflammation in the arrhythmogenesis of BrS and its underlying mechanism are still lacking. This study aimed to investigate the influence of inflammation on BrS-phenotype features using human-induced stem cell-derived cardiomyocytes (hiPSC-CMs) from a BrS-patient carrying an SCN10A variant (c.3749G > A). After LPS treatment, the peak sodium current decreased significantly in SCN10A-hiPSC-CMs, but not in healthy donor-hiPSC-CMs. LPS also changed sodium channel gating kinetics, including activation, inactivation, and recovery from inactivation. NAC (-acetyl-l-cysteine), a blocker of ROS (reactive oxygen species), failed to affect the sodium current, but prevented the LPS-induced reduction of sodium channel currents and changes in gating kinetics, suggesting a contribution of ROS to the LPS effects. Hydrogen peroxide (HO), a main form of ROS in cells, mimicked the LPS effects on sodium channel currents and gating kinetics, implying that ROS might mediate LPS-effects on sodium channels. The effects of HO could be attenuated by a PKC blocker chelerythrine, indicating that PKC is a downstream factor of ROS. This study demonstrated that LPS can exacerbate the loss-of-function of sodium channels in BrS cells. Inflammation may play an important role in the pathogenesis of BrS.
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http://dx.doi.org/10.3390/jcdd9040119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9025958PMC
April 2022

Antiarrhythmic Effects of Vernakalant in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes from a Patient with Short QT Syndrome Type 1.

J Cardiovasc Dev Dis 2022 Apr 9;9(4). Epub 2022 Apr 9.

Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention of Cardiovascular Diseases, Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646000, China.

(1) Background: Short QT syndrome (SQTS) may result in sudden cardiac death. So far, no drugs, except quinidine, have been demonstrated to be effective in some patients with SQTS type 1 (SQTS1). This study was designed to examine the potential effectiveness of vernakalant for treating SQTS1 patients, using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a patient with SQTS1. (2) Methods: Patch clamp and calcium imaging techniques were used to examine the drug effects. (3) Results: Vernakalant prolonged the action potential duration (APD) in hiPSC-CMs from a SQTS1-patient (SQTS1-hiPSC-CMs). In spontaneously beating SQTS1-hiPSC-CMs, vernakalant reduced the arrhythmia-like events induced by carbachol plus epinephrine. Vernakalant failed to suppress the hERG channel currents but reduced the outward small-conductance calcium-activated potassium channel current. In addition, it enhanced Na/Ca exchanger currents and late sodium currents, in agreement with its APD-prolonging effect. (4) Conclusions: The results demonstrated that vernakalant can prolong APD and reduce arrhythmia-like events in SQTS1-hiPSC-CMs and may be a candidate drug for treating arrhythmias in SQTS1-patients.
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http://dx.doi.org/10.3390/jcdd9040112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9032933PMC
April 2022

Efficacy and safety of high-power short duration atrial fibrillation ablation in elderly patients.

J Cardiovasc Electrophysiol 2022 07 6;33(7):1425-1434. Epub 2022 May 6.

Clinic for Interventional Electrophysiology, Heart Centre Bad Neustadt, Bad Neustadt a. d. Saale, Germany.

Introduction: Data about atrial fibrillation (AF) ablation using high-power short duration (HPSD) radiofrequency ablation in the elderly population is still scarce. The aim of our study was to investigate the efficacy and safety of HPSD ablation in patients over 75 years compared to younger patients.

Methods: Consecutive patients older than 75 years with paroxysmal or persistent AF undergoing a first-time AF ablation using 50 W HPSD ablation approach were analyzed in this retrospective observational analysis and compared to a control group <75 years. Short-term endpoints included intraprocedural reconnection of at least one pulmonary vein (PV) and intrahospital and AF recurrence during 3 months blanking period, as well as a long-term endpoint of freedom from atrial arrhythmias of antiarrhythmic drugs after 12 months.

Results: A total of 540 patients underwent a first AF ablation with HPSD (66 ± 10 years; 58% male; 47% paroxysmal AF). Mean age was 78 ± 2.4 and 63 ± 6.3 years (p < .001), respectively. Elderly patients were significantly more often women (p < .001). The procedure, fluoroscopy, and ablation were comparable. Elderly patients revealed significantly more often extra-PV low-voltage areas requiring additional left atrial ablations (p < .001). Overall complication rates were low; however, elderly patients revealed higher major complication rates mainly due to unmasking sick sinus syndrome (p = .003). Freedom from arrhythmia recurrences was comparable (68% vs. 76%, log-rank p = .087). Only in the subgroup of paroxysmal AF, AF recurrences were more common after 12 months (69% vs. 82%; log-rank p = .040; hazard ratio: 1.462, p = .044) in the elderly patients. In multivariable Cox regression analysis of the whole cohort persistent AF, female gender, diabetes mellitus and presence of left atrium low-voltage areas, but not age >75 years were associated with AF recurrences.

Conclusion: HPSD AF ablation of patients >75 years in experienced centers is safe and effective. Therefore, age alone should not be the reason to withhold AF ablation from vital elderly patients due to only a slightly worse outcome and safety profile. In paroxysmal AF, elderly patients have more recurrences compared to the younger control group.
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http://dx.doi.org/10.1111/jce.15504DOI Listing
July 2022

Adverse events and stroke prevention by interventional left atrial appendage occlusion in patients with low CHA DS -VASc score-results from the multicenter German LAARGE registry.

Catheter Cardiovasc Interv 2022 06 6;99(7):2064-2070. Epub 2022 Apr 6.

Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, European Center for AngioScience (ECAS), and German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheim, Mannheim, Germany.

Background: Interventional left atrial appendage occlusion (LAAO) is routinely performed in patients with nonvalvular atrial fibrillation and contraindications to standard anticoagulation.

Aims: We investigated its role in patients at low stroke risk, and compared the effectiveness and safety in patients with low versus high risk.

Methods: LAARGE is a prospective registry depicting the clinical reality of LAAO. LAAO was conducted with different standard commercial devices, and follow-up period was 1 year. Patients with started procedure and documented CHA DS -VASc score were selected from the whole database.

Results: A total of 638 patients from 38 centers were divided into CHA DS -VASc score ≤2, i.e., low-risk group (10.2%), and >2, i.e., high-risk group (89.8%). The latter had a pronounced cardiovascular risk profile and preceding strokes (0% vs. 23.9%; p < 0.001). Implantation success was consistently high (97.6%), frequencies of intrahospital major adverse cardiac and cerebrovascular events (0% vs. 0.5%) and other major complications (4.6% vs. 4.0%) were low (each p = not significant [NS]). Numerous moderate complications were also observed in the low-risk patients (12.3% vs. 9.4%; p = NS). Frequencies of nonfatal strokes (0% vs. 0.7%) and severe bleedings (0% vs. 0.7%) were low (each p = NS). In a specific analysis, patients at very high risk of stroke (i.e., CHA DS -VASc score >4) did not have increased rates of complications or nonfatal strokes in the first year after the procedure.

Conclusions: Low-risk patients had no nonfatal strokes and major bleedings within 1 year after hospital discharge but had unexpectedly high rates of moderate procedural complications. The indication in these patients should be strictly defined based on an individual benefit-risk assessment.
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http://dx.doi.org/10.1002/ccd.30165DOI Listing
June 2022

Cardiac disease and prognosis associated with ventricular tachyarrhythmias in young adults and adults.

BMC Cardiovasc Disord 2022 03 31;22(1):136. Epub 2022 Mar 31.

Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.

Background: This study evaluates cardiac diseases and prognosis in young adults and adults presenting with ventricular tachyarrhythmias (VTA).

Methods: The present longitudinal, observational, registry-based, monocentric cohort study includes all consecutive patients 45 years old or younger presenting with VTA at admission from 2002 to 2016. Rates of coronary angiography, coronary artery disease (CAD) and need for percutaneous coronary intervention (PCI), cardiac diseases associated with VTA, and differences in long-term prognostic endpoints for young adults (20-34 years old) were analyzed and compared to those of adults (35-45 years old), for whom multivariable risk prediction models were developed. Kaplan-Meier analyses were performed according to age and type of VTA.

Results: A total of 259 consecutive patients were included in the study (36% young adults and 64% adults). At admission, 38% of young adults had VTA due to CAD that required PCI. Furthermore, VTA in young adults was commonly idiopathic (27%), or had underlying channelopathies (18%), primary cardiomyopathies (13%) or acute myocardial infarction (AMI, 11%). In adults, VTA was mostly associated with AMI (28%), though the rate of idiopathy was still high (20%). A total 41% of all patients received cardiopulmonary resuscitation (CPR), for whom AMI (STEMI 17%, NSTEMI 24%) was most frequently observed. Irrespective of the type of VTA, all-cause mortality was similar for young adults and adults. In young adults, left ventricular ejection fraction (LVEF) < 35% (HR = 33.590) was associated with increased long-term all-cause mortality.

Conclusion: Despite high rates of idiopathic ventricular tachyarrhythmias, CAD and AMI are common causes of VTA and CPR in adults 45 years old and younger. Young adults and adults had comparable survival at index hospitalization and after 2.5 years irrespective of the type of VTA. Clinical trial registration clinicaltrials.gov identifier: NCT02982473.
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http://dx.doi.org/10.1186/s12872-022-02552-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8973880PMC
March 2022

Thalassaemia is paradoxically associated with a reduced risk of in-hospital complications and mortality in COVID-19: Data from an international registry.

J Cell Mol Med 2022 05 30;26(9):2520-2528. Epub 2022 Mar 30.

Policlinico Umberto I, Rome, Italy.

Although numerous patient-specific co-factors have been shown to be associated with worse outcomes in COVID-19, the prognostic value of thalassaemic syndromes in COVID-19 patients remains poorly understood. We studied the outcomes of 137 COVID-19 patients with a history of transfusion-dependent thalassaemia (TDT) and transfusion independent thalassaemia (TIT) extracted from a large international cohort and compared them with the outcomes from a matched cohort of COVID-19 patients with no history of thalassaemia. The mean age of thalassaemia patients included in our study was 41 ± 16 years (48.9% male). Almost 81% of these patients suffered from TDT requiring blood transfusions on a regular basis. 38.7% of patients were blood group O. Cardiac iron overload was documented in 6.8% of study patients, whereas liver iron overload was documented in 35% of study patients. 40% of thalassaemia patients had a history of splenectomy. 27.7% of study patients required hospitalization due to COVID-19 infection. Amongst the hospitalized patients, one patient died (0.7%) and one patient required intubation. Continuous positive airway pressure (CPAP) was required in almost 5% of study patients. After adjustment for age-, sex- and other known risk factors (cardiac disease, kidney disease and pulmonary disease), the rate of in-hospital complications (supplemental oxygen use, admission to an intensive care unit for CPAP therapy or intubation) and all-cause mortality was significantly lower in the thalassaemia group compared to the matched cohort with no history of thalassaemia. Amongst thalassaemia patients in general, the TIT group exhibited a higher rate of hospitalization compared to the TDT group (p = 0.001). In addition, the rate of complications such as acute kidney injury and need for supplemental oxygen was significantly higher in the TIT group compared to the TDT group. In the multivariable logistic regression analysis, age and history of heart or kidney disease were all found to be independent risk factors for increased in-hospital, all-cause mortality, whereas the presence of thalassaemia (either TDT or TIT) was found to be independently associated with reduced all-cause mortality. The presence of thalassaemia in COVID-19 patients was independently associated with lower in-hospital, all-cause mortality and few in-hospital complications in our study. The pathophysiology of this is unclear and needs to be studied in vitro and in animal models.
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http://dx.doi.org/10.1111/jcmm.17026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9077285PMC
May 2022

Hemodynamic Effects of Sacubitril/Valsartan in Patients with Reduced Left Ventricular Ejection Fraction Over 24 Months: A Retrospective Study.

Am J Cardiovasc Drugs 2022 Mar 30. Epub 2022 Mar 30.

Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.

Background: The effects of sacubitril/valsartan in patients with chronic heart failure with reduced ejection fraction (HFrEF) were recently reported. However, the hemodynamic impact of this well-established treatment in patients with HFrEF has been poorly systematically researched.

Aim: We aimed to investigate the hemodynamic effects of sacubitril/valsartan among patients with HFrEF.

Methods: Between 2016 and 2020, we retrospectively collected data for patients with HFrEF treated at the University Medical Center Mannheim, Germany. Data for 240 patients with HFrEF were available. We systematically analyzed echocardiographic parameters, all-cause hospitalization, and congestion rate.

Results: The left ventricular ejection fraction (LVEF) improved from a median (minimum; maximum) of 28% (3; 65) before initiation of sacubitril/valsartan to a median of 34% (13; 64) at 24-month follow-up (p < 0.001). Systolic pulmonary atrial pressure (PAPsys) decreased from a median of 30 mmHg (13; 115) to 25 mmHg (20; 80) at 24-month follow-up (p = 0.005). The median (minimum; maximum) tricuspid annular plane systolic excursion improved from 17 mm (3; 31) at baseline to 20 mm (9; 30) at 12-month follow-up (p = 0.007). The incidence of severe and moderate mitral, tricuspid, and aortic valvular insufficiency improved after treatment. Hospitalization and congestion rates reduced at 24-month follow-up. The mortality rate in echocardiographic and functional nonresponders was higher than in responders (12.1 vs. 5.2%; p = 0.1 and 11.3 vs. 3.1%; p = 0.01, respectively).

Conclusion: Follow-up 24 months after starting treatment with sacubitril/valsartan revealed sustained improvements in echocardiographic parameters, including LVEF, PAPsys, and cardiac valvular insufficiency. Rates of all-cause hospitalization and congestion had decreased significantly at follow-up. The mortality rate was higher in echocardiographic and functional nonresponders.
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http://dx.doi.org/10.1007/s40256-022-00525-wDOI Listing
March 2022

Severe Acute Respiratory Distress Syndrome (ARDS) or Severely Increased Chest Wall Elastance?

Cureus 2022 Feb 23;14(2):e22541. Epub 2022 Feb 23.

Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Center Mannheim, Mannheim, DEU.

Esophageal manometry can be used to calculate transpulmonary pressures and optimize ventilator settings accordingly. We present the case of a 31-year-old male patient with ataxia-telangiectasia (Louis-Bar syndrome) and a BMI of 20 kg/m, admitted to our intensive care unit for coronavirus disease 2019 (COVID-19) pneumonia. The patient soon required mechanical ventilation; however, there was very poor respiratory system compliance. Cholecystitis complicated the clinical course, and veno-venous extracorporeal membrane oxygenation (ECMO) was initiated as gas exchange deteriorated. Esophageal manometry was introduced and revealed severely increased intrathoracic pressure and chest wall elastance.
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http://dx.doi.org/10.7759/cureus.22541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8956486PMC
February 2022

A Case Series of Concomitant Cardiac Electrical Disease among Takotsubo Syndrome Patients and Literature Review.

J Cardiovasc Dev Dis 2022 Mar 9;9(3). Epub 2022 Mar 9.

First Department of Medicine, Faculty of Medicine, University Medical Centre Mannheim (UMM), University of Heidelberg, 68167 Mannheim, Germany.

The pathophysiology of Takotsubo Syndrome (TTS) is not completely understood and the trigger of sudden cardiac death (SCD) in TTS is not clear either. We therefore sought to find an association between TTS and primary electrical diseases. A total of 148 TTS patients were analyzed between 2003 and 2017 in a bi-centric manner. Additionally, a literature review was performed. The patients were included in an ongoing retrospective cohort database. The coexistence of TTS and primary electrical diseases was confirmed in five cases as the following: catecholaminergic polymorphic ventricular tachycardia (CPVT, 18-year-old female) ( = 1), LQTS 1 (72-year-old female and 65-year-old female) ( = 2), LQTS 2 (17-year-old female) ( = 1), and LQTS in the absence of mutations (22-year-old female). Four patients suffered from malignant tachyarrhythmia and recurrent syncope after TTS. Except for the CPVT patient and one LQTS 1 patient, all other cases underwent subcutaneous ICD implantation. An event recorder of the CPVT patient after starting beta-blocker did not detect arrhythmias. The diagnosis of primary electrical disease was in 80% of cases unmasked on a TTS event. This diagnosis triggered a family clinical and genetic screening confirming the diagnosis of primary electrical disease. A subsequent literature review identified five cases as the following: a congenital atrioventricular block ( = 1), a Jervell and Lange-Nielsen Syndrome ( = 1), and a family LQTS in the absence of a mutation ( = 2), LQTS 2 ( = 1). A primary electrical disease should be suspected in young and old TTS patients with a family history of sudden cardiac death. In suspected cases, e.g., ongoing QT interval prolongation, despite recovery of left ventricular ejection fraction a family screening is recommended.
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http://dx.doi.org/10.3390/jcdd9030079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8955983PMC
March 2022

Glucose Counteracts Isoprenaline Effects on Ion Channel Functions in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

J Cardiovasc Dev Dis 2022 Mar 4;9(3). Epub 2022 Mar 4.

Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim (UMM), University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.

Recent studies indicate that the disorder of glucose metabolism in myocardial tissue is involved in the development of Takotsubo syndrome (TTS). This study investigated the effects of a high level of glucose on the pathogenesis of TTS, focusing on the electrophysiological mechanisms. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were treated with toxic concentration of isoprenaline (Iso, 1 mM) and a high level of glucose (22 mM) to mimic the setting of TTS and diabetes mellitus (DM). Iso prolonged action potential duration (APD) through enhancing the late sodium channel current and suppressing the transient outward potassium current (I). However, a high level of glucose prevented the APD prolongation and the change in I. High-level glucose reduced the expression levels of PI3K/Akt, β1-adrenoceptors, Gs-protein, and PKA, suggesting their involvement in the protective effects of high-level glucose against toxic effects of catecholamine. High glucose level did not influence Iso-induced ROS-generation, suggesting that the protective effects of high-level glucose against Iso did not result from changes in ROS generation. High-level glucose may protect cardiomyocytes from the toxic effects of catecholamine excess through suppressing β1-adrenoceptor-Gs-PKA signaling. DM may reduce the risk for occurrence of arrhythmias due to QT prolongation in TTS patients.
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http://dx.doi.org/10.3390/jcdd9030076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8955312PMC
March 2022

Brugada Syndrome: Different Experimental Models and the Role of Human Cardiomyocytes From Induced Pluripotent Stem Cells.

J Am Heart Assoc 2022 04 24;11(7):e024410. Epub 2022 Mar 24.

First Department of Medicine Medical Faculty Mannheim University Medical Centre Mannheim (UMM)University of Heidelberg Mannheim Germany.

Brugada syndrome (BrS) is an inherited and rare cardiac arrhythmogenic disease associated with an increased risk of ventricular fibrillation and sudden cardiac death. Different genes have been linked to BrS. The majority of mutations are located in the gene, and the typical abnormal ECG is an elevation of the ST segment in the right precordial leads V1 to V3. The pathophysiological mechanisms of BrS were studied in different models, including animal models, heterologous expression systems, and human-induced pluripotent stem cell-derived cardiomyocyte models. Currently, only a few BrS studies have used human-induced pluripotent stem cell-derived cardiomyocytes, most of which have focused on genotype-phenotype correlations and drug screening. The combination of new technologies, such as clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 (CRISPR associated protein 9)-mediated genome editing and 3-dimensional engineered heart tissues, has provided novel insights into the pathophysiological mechanisms of the disease and could offer opportunities to improve the diagnosis and treatment of patients with BrS. This review aimed to compare different models of BrS for a better understanding of the roles of human-induced pluripotent stem cell-derived cardiomyocytes in current BrS research and personalized medicine at a later stage.
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http://dx.doi.org/10.1161/JAHA.121.024410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9075459PMC
April 2022

Angiotensin Converting Enzyme Inhibitors versus Receptor Blockers in Patients with Ventricular Tachyarrhythmias.

J Clin Med 2022 Mar 7;11(5). Epub 2022 Mar 7.

First Department of Medicine, University Medical Centre Mannheim (UMM), Faculty of Medicine Mannheim, University of Heidelberg, DZHK (German Center for Cardiovascular Research) Partner Site Heidelberg/Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.

Data investigating the prognostic value of treatment with angiotensin converting enzyme inhibitors (ACEi) and receptor blockers (ARB) usually focusses on patients presenting with heart failure (HF) or acute myocardial infarction (AMI). However, by preventing adverse cardiac remodeling, ACEi/ARB may also decrease the risk of ventricular tachyarrhythmias and sudden cardiac death (SCD). Although ventricular tachyarrhythmias are associated with significant mortality and morbidity, only limited data are available focusing on the prognostic role of ACEi/ARB, when prescribed for secondary prevention of SCD. Therefore, this study comprehensively investigates the role of ACEi versus ARB in patients with ventricular tachyarrhythmias. A large retrospective registry was used including consecutive patients with episodes of ventricular tachycardia (VT) or fibrillation (VF) from 2002 to 2015. The primary prognostic outcome was all-cause mortality at three years, secondary endpoints comprised a composite arrhythmic endpoint (i.e., recurrences of ventricular tachyarrhythmias, ICD therapies and sudden cardiac death) and cardiac rehospitalization. A total of 1236 patients were included (15% treated with ARB and 85% with ACEi) and followed for a median of 4.0 years. At three years, ACEi and ARB were associated with comparable long-term mortality (20% vs. 17%; log rank = 0.287; HR = 0.965; 95% CI 0.689-1.351; = 0.835) and comparable risk of the composite arrhythmic endpoint (HR = 1.227; 95% CI 0.841-1.790; = 0.288). In contrast, ACEi was associated with a decreased risk of cardiac rehospitalization at three years (HR = 0.690; 95% CI 0.490-0.971; = 0.033). Within the propensity score matched cohort (i.e., 158 patients with ACEi and ARB), ACEi and ARB were associated with comparable long-term outcomes at three years. In conclusion, ACEi and ARB are associated with comparable risk of long-term outcomes in patients presenting with ventricular tachyarrhythmias.
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http://dx.doi.org/10.3390/jcm11051460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8910841PMC
March 2022

Regulation of Ion Channel Function in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes by Cancer Cell Secretion Through DNA Methylation.

Front Cardiovasc Med 2022 21;9:839104. Epub 2022 Feb 21.

First Department of Medicine, Medical Faculty Mannheim, University Medical Centre Mannheim (UMM), University of Heidelberg, Mannheim, Germany.

Background: Cardiac dysfunction including arrhythmias appear frequently in patients with cancers, which are expected to be caused mainly by cardiotoxic effects of chemotherapy. Experimental studies investigating the effects of cancer cell secretion without chemotherapy on ion channel function in human cardiomyocytes are still lacking.

Methods: The human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) generated from three healthy donors were treated with gastrointestinal (GI) cancer (AGS and SW480 cells) medium for 48 h. The qPCR, patch-clamp, western blotting, immunostaining, dot blotting, bisulfite sequence, and overexpression of the ten-eleven translocation (TET) enzyme were performed for the study.

Results: After treated with cancer cell secretion, the maximum depolarization velocity and the action potential amplitude were reduced, the action potential duration prolonged, peak Na current, and the transient outward current were decreased, late Na and the slowly activating delayed rectifier K current were increased. Changes of mRNA and protein level of respective channels were detected along with altered DNA methylation level in CpG island in the promoter regions of ion channel genes and increased protein levels of DNA methyltransferases. Phosphoinositide 3-kinase (PI3K) inhibitor attenuated and transforming growth factor-β (TGF-β) mimicked the effects of cancer cell secretion.

Conclusions: GI cancer cell secretion could induce ion channel dysfunction, which may contribute to occurrence of arrhythmias in cancer patients. The ion channel dysfunction could result from DNA methylation of ion channel genes activation of TGF-β/PI3K signaling. This study may provide new insights into pathogenesis of arrhythmia in cancer patients.
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http://dx.doi.org/10.3389/fcvm.2022.839104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899119PMC
February 2022
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