Publications by authors named "Martin Manninger"

32 Publications

Current perspectives on wearable rhythm recordings for clinical decision-making: the wEHRAbles 2 survey.

Europace 2021 Apr 11. Epub 2021 Apr 11.

Hannover Heart Rhythm Center, Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.

Novel wearable devices for heart rhythm analysis using either photoplethysmography (PPG) or electrocardiogram (ECG) are in daily clinical practice. This survey aimed to assess impact of these technologies on physicians' clinical decision-making and to define, how data from these devices should be presented and integrated into clinical practice. The online survey included 22 questions, focusing on the diagnosis of atrial fibrillation (AF) based on wearable rhythm device recordings, suitable indications for wearable rhythm devices, data presentation and processing, reimbursement, and future perspectives. A total of 539 respondents {median age 38 [interquartile range (IQR) 34-46] years, 29% female} from 51 countries world-wide completed the survey. Whilst most respondents would diagnose AF (83%), fewer would initiate oral anticoagulation therapy based on a single-lead ECG tracing. Significantly fewer still (27%) would make the diagnosis based on PPG-based tracing. Wearable ECG technology is acceptable for the majority of respondents for screening, diagnostics, monitoring, and follow-up of arrhythmia patients, while respondents were more reluctant to use PPG technology for these indications. Most respondents (74%) would advocate systematic screening for AF using wearable rhythm devices, starting at patients' median age of 60 (IQR 50-65) years. Thirty-six percent of respondents stated that there is no reimbursement for diagnostics involving wearable rhythm devices in their countries. Most respondents (56.4%) believe that costs of wearable rhythm devices should be shared between patients and insurances. Wearable single- or multiple-lead ECG technology is accepted for multiple indications in current clinical practice and triggers AF diagnosis and treatment. The unmet needs that call for action are reimbursement plans and integration of wearable rhythm device data into patient's files and hospital information systems.
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http://dx.doi.org/10.1093/europace/euab064DOI Listing
April 2021

The European TeleCheck-AF project on remote app-based management of atrial fibrillation during the COVID-19 pandemic: centre and patient experiences.

Europace 2021 Apr 2. Epub 2021 Apr 2.

Department of Cardiology, Maastricht University Medical Centre, Cardiovascular Research Institute Maastricht, 6202 AZ Maastricht, The Netherlands.

Aims: TeleCheck-AF is a multicentre international project initiated to maintain care delivery for patients with atrial fibrillation (AF) during COVID-19 through teleconsultations supported by an on-demand photoplethysmography-based heart rate and rhythm monitoring app (FibriCheck®). We describe the characteristics, inclusion rates, and experiences from participating centres according the TeleCheck-AF infrastructure as well as characteristics and experiences from recruited patients.

Methods And Results: Three surveys exploring centre characteristics (n = 25), centre experiences (n = 23), and patient experiences (n = 826) were completed. Self-reported patient characteristics were obtained from the app. Most centres were academic (64%) and specialized public cardiology/district hospitals (36%). Majority of the centres had AF outpatient clinics (64%) and only 36% had AF ablation clinics. The time required to start patient inclusion and total number of included patients in the project was comparable for centres experienced (56%) or inexperienced in mHealth use. Within 28 weeks, 1930 AF patients were recruited, mainly for remote AF control (31% of patients) and AF ablation follow-up (42%). Average inclusion rate was highest during the lockdown restrictions and reached a steady state at a lower level after easing the restrictions (188 vs. 52 weekly recruited patients). Majority (>80%) of the centres reported no problems during the implementation of the TeleCheck-AF approach. Recruited patients [median age 64 (55-71), 62% male] agreed that the FibriCheck® app was easy to use (94%).

Conclusion: Despite different health care settings and mobile health experiences, the TeleCheck-AF approach could be set up within an extremely short time and easily used in different European centres during COVID-19.
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http://dx.doi.org/10.1093/europace/euab050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083545PMC
April 2021

No antiarrhythmic effect of direct oral anticoagulants versus vitamin K antagonists in paroxysmal atrial fibrillation patients undergoing catheter ablation.

Int J Cardiol 2021 May 26;331:106-108. Epub 2021 Jan 26.

Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Austria; Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, Limburg, the Netherlands.

Introduction: Direct oral anticoagulants (DOACs) are superior to vitamin K antagonists (VKAs) for the prevention of stroke in atrial fibrillation (AF) patients with elevated stroke risk. Possible antiarrhythmic effects of DOACs have been discussed. We analyzed impact of DOAC treatment on recurrence-free survival after AF catheter ablation.

Methods: Two-hundred and thirty-nine consecutive patients (median age 57 [IQR 48-64] years, 26.4% female) undergoing ablation for paroxysmal AF were included into this study. 68.6% of them received DOACs (DOAC group), 31.4% VKA (VKA group). The primary outcome was arrhythmia-free one-year survival.

Results: DOAC patients had lower BMI, shorter history of AF, less arterial hypertension, less vascular disease, less use of antiarrhythmics and consequently lower CHADS-VASc and HAS-BLED Scores. There was no difference in arrhythmia-free survival between DOAC and VKA groups (DOAC: 86.6%, VKA: 76.7%, p = 0.286).

Conclusions: Despite baseline characteristics favouring a better outcome of DOAC patients, arrhythmia-free survival was similar in both groups. Consequently, DOAC treatment did not have clinically relevant antiarrhythmic properties in these patients.
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http://dx.doi.org/10.1016/j.ijcard.2021.01.003DOI Listing
May 2021

Trends beyond the new normal: from remote monitoring to digital connectivity.

Eur Heart J Suppl 2020 Dec 23;22(Suppl Pt t):P8-P12. Epub 2020 Dec 23.

Clinical Department of Cardiology, University of Graz, Graz, Austria.

COVID pandemic emergency has forced changes from traditional in-person visits to application of telemedicine in order to overcome the barriers and to deliver care. COVID-19 has accelerated adoption of digital health. During this time, the distance is itself a prevention tool and the use of technology to deliver healthcare services and information has driven the discovery of mobile and connected health services. Health services should to be prepared to integrate the old model of remote monitoring of CIEDs and adopt new digital tools such as mobile Apps and connected sensors.
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http://dx.doi.org/10.1093/eurheartj/suaa170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757717PMC
December 2020

Cellular contribution to left and right atrial dysfunction in chronic arterial hypertension in pigs.

ESC Heart Fail 2021 Feb 29;8(1):151-161. Epub 2020 Nov 29.

Department of Internal Medicine and Cardiology, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburgerplatz 1, Berlin, 13353, Germany.

Aims: Atrial contractile dysfunction contributes to worse prognosis in hypertensive heart disease (HHD), but the role of cardiomyocyte dysfunction in atrial remodelling in HHD is not well understood. We investigated and compared cellular mechanisms of left (LA) and right atrial (RA) contractile dysfunction in pigs with HHD.

Methods And Results: In vivo electrophysiological and magnetic resonance imaging studies were performed in control and pigs treated with 11-deoxycorticosterone acetate (DOCA)/high-salt/glucose diet (12 weeks) to induce HHD. HHD leads to significant atrial remodelling and loss of contractile function in LA and a similar trend in RA (magnetic resonance imaging). Atrial remodelling was associated with a higher inducibility of atrial fibrillation but unrelated to changes in atrial refractory period or fibrosis (histology). Reduced atrial function in DOCA pigs was related to reduced contraction amplitude of isolated LA (already at baseline) and RA myocytes (at higher frequencies) due to reduced intracellular Ca release (Fura 2-AM, field stimulation). However, Ca regulation differed in LA and RA cardiomyocytes: LA cardiomyocytes showed reduced sarcoplasmic reticulum (SR) [Ca], whereas in RA, SR [Ca] was unchanged and SR Ca -ATPase activity was increased. Sodium-calcium exchanger (NCX) activity was not significantly altered. We used ORM-10103 (3 μM), a specific NCX inhibitor to improve Ca availability in LA and RA cardiomyocytes from DOCA pigs. Partial inhibition of NCX increased Ca transient amplitude and SR Ca in LA, but not RA cells.

Conclusions: In this large animal model of HHD, atrial remodelling in sinus rhythm in vivo was related to differential LA and RA cardiomyocyte dysfunction and Ca signalling. Selective acute inhibition of NCX improved Ca release in diseased LA cardiomyocytes, suggesting a potential therapeutic approach to improve atrial inotropy in HHD.
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http://dx.doi.org/10.1002/ehf2.13087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835565PMC
February 2021

On-demand mobile health infrastructures to allow comprehensive remote atrial fibrillation and risk factor management through teleconsultation.

Clin Cardiol 2020 Nov 8;43(11):1232-1239. Epub 2020 Oct 8.

Department of Cardiology, Maastricht University Medical Centre and Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands.

Background: Although novel teleconsultation solutions can deliver remote situations that are relatively similar to face-to-face interaction, remote assessment of heart rate and rhythm as well as risk factors remains challenging in patients with atrial fibrillation (AF).

Hypothesis: Mobile health (mHealth) solutions can support remote AF management.

Methods: Herein, we discuss available mHealth tools and strategies on how to incorporate the remote assessment of heart rate, rhythm and risk factors to allow comprehensive AF management through teleconsultation.

Results: Particularly, in the light of the coronavirus disease 2019 (COVID-19) pandemic, there is decreased capacity to see patients in the outpatient clinic and mHealth has become an important component of many AF outpatient clinics. Several validated mHealth solutions are available for remote heart rate and rhythm monitoring as well as for risk factor assessment. mHealth technologies can be used for (semi-)continuous longitudinal monitoring or for short-term on-demand monitoring, dependent on the respective requirements and clinical scenarios. As a possible solution to improve remote AF care through teleconsultation, we introduce the on-demand TeleCheck-AF mHealth approach that allows remote app-based assessment of heart rate and rhythm around teleconsultations, which has been developed and implemented during the COVID-19 pandemic in Europe.

Conclusion: Large scale international mHealth projects, such as TeleCheck-AF, will provide insight into the additional value and potential limitations of mHealth strategies to remotely manage AF patients. Such mHealth infrastructures may be well suited within an integrated AF-clinic, which may require redesign of practice and reform of health care systems.
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http://dx.doi.org/10.1002/clc.23469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661648PMC
November 2020

Survey of current perspectives on consumer-available digital health devices for detecting atrial fibrillation.

Cardiovasc Digit Health J 2020 Jul-Aug;1(1):21-29. Epub 2020 Aug 28.

Division of Cardiology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts.

Background: Many digital health technologies capable of atrial fibrillation (AF) detection are directly available to patients. However, adaptation into clinical practice by heart rhythm healthcare practitioners (HCPs) is unclear.

Objective: To examine HCP perspectives on use of commercial technologies for AF detection and management.

Methods: We created an electronic survey for HCPs assessing practice demographics and perspectives on digital devices for AF detection and management. The survey was distributed electronically to all members of 3 heart rhythm professional societies.

Results: We received 1601 responses out of 73,563 e-mails sent, with 43.6% from cardiac electrophysiologists, 12.8% from fellows, and 11.6% from advanced practice practitioners. Most respondents (62.3%) reported having recommended patient use of a digital device for AF detection. Those who did not had concerns about their accuracy (29.6%), clinical utility of results (22.8%), and integration into electronic health records (19.8%). Results from a 30-second single-lead electrocardiogram were sufficient for 42.7% of HCPs to recommend oral anticoagulation for patients at high risk for stroke. Respondents wanted more data comparing the accuracy of digital devices to conventional devices for AF monitoring (64.9%). A quarter (27.3%) of HCPs had no reservations recommending digital devices for AF detection, and most (53.4%) wanted guidelines from their professional societies providing guidance on their optimal use.

Conclusion: Many HCPs have already integrated digital devices into their clinical practice. However, HCPs reported facing challenges when using digital technologies for AF detection, and professional society recommendations on their use are needed.
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http://dx.doi.org/10.1016/j.cvdhj.2020.06.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452829PMC
August 2020

Role of wearable rhythm recordings in clinical decision making-The wEHRAbles project.

Clin Cardiol 2020 Sep 22;43(9):1032-1039. Epub 2020 Jul 22.

Hannover Heart Rhythm Center, Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.

Background: Multiple wearable devices for rhythm analysis have been developed using either photoplethysmography (PPG) or handheld ECG.

Hypothesis: The aim of this survey was to assess impact of these technologies on physicians' clinical decision-making regarding initiation of diagnostic steps, drug therapy, and invasive strategies.

Methods: The online survey included 10 questions on types of devices, advantages, and disadvantages of wearable devices as well as case scenarios for patients with supraventricular arrhythmias and atrial fibrillation (AF).

Results: A total of 417 physicians (median age 37 [IQR 32-43] years) from 42 countries world-wide completed the survey. When presented a tracing of a regular tachycardia by a symptomatic patient, most participants would trigger further diagnostic steps (90% for single-lead ECG vs 83% for PPG, P < .001), while a single-lead ECG would be sufficient to perform an invasive EP study in approximately half of participants (51% vs 22% for PPG, P < .001). When presented with a single-lead ECG tracing suggesting AF, most participants (90%) would trigger further diagnostic steps. A symptomatic AF patient would trigger anticoagulation treatment to a higher extent as an asymptomatic patient (59% vs 21%, P < .001). PPG tracings would only rarely lead to therapeutic steps regardless of symptoms. Most participants would like scientific society recommendations on the use of wearable devices (62%).

Conclusions: Tracings from wearable rhythm devices suggestive of arrhythmias are most likely to trigger further diagnostic steps, and in the case of PPG recordings rarely therapeutic interventions. A majority of participants expect these devices to facilitate diagnostics and arrhythmia screening but fear data overload and expect scientific society recommendations on the use of wearables.
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http://dx.doi.org/10.1002/clc.23404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462183PMC
September 2020

Acute hyperglycaemia is not associated with the development of atrial fibrillation in healthy pigs.

Sci Rep 2020 07 17;10(1):11881. Epub 2020 Jul 17.

Department of Cardiology, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria.

Development and progression of atrial fibrillation (AF) is driven by comorbidities such as arterial hypertension and diabetes mellitus. In animal models of chronic hyperglycaemia, progression of AF has been proposed to be triggered by oxidative stress, apoptosis and fibrosis. Acute glycosylation of CaMKII has been associated with increased susceptibility to arrhythmias in acute hyperglycaemia. However, the proarrhythmogenic effect of acute hyperglycaemia has not been investigated. Nine healthy, anesthetized pigs (54 ± 6 kg) were instrumented with electrophysiologic catheters and a multielectrode array on the epicardium of the left atrial anterior wall. Left and right atrial effective refractory periods (AERP), inducibility of AF and left atrial epicardial conduction velocities (CV) were measured at baseline (BL), increasing steps of blood glucose (200-500 mg/dL in steps of 100 mg/dL by glucose infusion) and repeated after normalisation of blood glucose levels (recovery). Serum electrolytes were kept constant during measurements by means of sodium and potassium infusion. There were no significant differences in AERP, CV or AF inducibility between BL and recovery. Heart rate remained constant regardless of blood glucose levels (BL: 103 ± 18 bpm, 500 mg/dL: 103 ± 18 bpm, r = 0.02, p = 0.346). Mean left as well as right AERP increased with higher glucose levels. CV increased with glucose levels (1.25 (1.04, 1.67) m/s at BL vs. 1.53 (1.22, 2.15) m/s at 500 mg/dL, r = 0.85, p = 0.034). Rate of AF inducibility in the left atrium remained constant throughout the whole protocol (AF episodes > 10 s: mean inducibility of 80% at BL vs. 69% at 500 mg/dL, p = 0.32, episodes > 30 s: 0% at BL vs. 0% at 500 mg/dL, p = 0.17). Our data imply that acute hyperglycaemia is associated with lower arrhythmogenic substrate and does not promote AF inducibility.
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http://dx.doi.org/10.1038/s41598-020-68897-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367844PMC
July 2020

T and T mapping in ex situ porcine myocardium: myocardial intravariability, temporal stability and the effects of complete coronary occlusion.

Int J Legal Med 2020 Mar 18;134(2):679-690. Epub 2019 Dec 18.

Ludwig Boltzmann Institute for Clinical Forensic Imaging, Graz, Austria.

Diagnosis of ischaemia-related sudden cardiac death in the absence of microscopic and macroscopic ischaemic lesions remains a challenge for medical examiners. Medical imaging techniques increasingly provide support in post-mortem examinations by detecting and documenting internal findings prior to autopsy. Previous studies have characterised MR relaxation times to investigate post-mortem signs of myocardial infarction in forensic cohorts. In this prospective study based on an ex situ porcine heart model, we report fundamental findings related to intramyocardial variability and temporal stability of T as well as the effects of permanent coronary occlusion on T and T relaxation in post-mortem myocardium. The ex situ porcine hearts included in this study (n= 19) were examined in two groups (S, n= 11 and S, n= 8). All magnetic resonance imaging (MRI) examinations were performed ex situ, at room temperature and at 3 T. In the S group, T mapping was performed on slaughterhouse porcine hearts at different post-mortem intervals (PMI) between 7 and 26 h. Regarding the intramyocardial variability, no statistically significant differences in T were observed between myocardial segments (p= 0.167). Assessment of temporal stability indicated a weak negative correlation (r=- 0.21) between myocardial T and PMI. In the S group, animals underwent ethanol-induced complete occlusion of the left anterior descending artery. T and T mapping were performed within 3 h of death. Differences between the expected ischaemic and remote regions were statistically significant for T (p= 0.007), however not for T (p= 0.062). Our results provide important information for future assessment of the diagnostic potential of quantitative MRI in the post-mortem detection of early acute myocardial infarction.
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http://dx.doi.org/10.1007/s00414-019-02211-0DOI Listing
March 2020

A transmural gradient of myocardial remodeling in early-stage heart failure with preserved ejection fraction in the pig.

J Anat 2020 03 21;236(3):531-539. Epub 2019 Nov 21.

Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.

Heart failure with preserved ejection fraction (HFpEF) is characterized by diastolic dysfunction. This study aimed to analyze whether early HFpEF is already associated with ultrastructural alterations and whether they differ quantitatively among the layers of the left ventricular wall. HFpEF was induced in pigs by deoxy-corticosterone acetate (DOCA) treatment along with a high-salt/high lipid diet over 3 months and compared with weight-matched normal pigs (n = 5 each). Samples of the left ventricle were taken and processed for light and electron microscopy. Interstitial fibrosis, subcellular composition of cardiomyocytes and mean cardiomyocyte diameter were evaluated by stereology in subendocardial, midmyocardial and subepicardial regions. DOCA enhanced the mean cardiomyocyte diameter in all locations of the ventricle wall to the same degree. The subcellular composition did not differ between the locations and was not altered by DOCA. The volume fraction of interstitium was smaller in the subendocardium of DOCA group than of control group. Within the interstitium, the volume fraction of collagen fibrils (between cardiomyocytes) was increased in the subendocardial and midmyocardial wall layers of the DOCA group but not in the subepicardial layer. Although the capillary length density and average supply area were not altered in response to DOCA in any of the wall layers, the volume fraction of blood vessels related to the interstitial space was enhanced in the subendocardium of the DOCA group but not in the other wall layers. In conclusion, cardiomyocyte changes due to DOCA were similar in subepicardial, midmyocardial and subendocardial regions but DOCA-induced changes in the interstitium appeared to be more pronounced in the subendocardial ventricular wall layers. This suggests a pivotal role of the subendocardial interstitium in the pathogenesis of HFpEF.
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http://dx.doi.org/10.1111/joa.13117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7018631PMC
March 2020

Cardiac power output accurately reflects external cardiac work over a wide range of inotropic states in pigs.

BMC Cardiovasc Disord 2019 10 15;19(1):217. Epub 2019 Oct 15.

Department of Internal Medicine and Cardiology, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburgerplatz 1, 13353, Berlin, Germany.

Background: Cardiac power output (CPO), derived from the product of cardiac output and mean aortic pressure, is an important yet underexploited parameter for hemodynamic monitoring of critically ill patients in the intensive-care unit (ICU). The conductance catheter-derived pressure-volume loop area reflects left ventricular stroke work (LV SW). Dividing LV SW by time, a measure of LV SW min is obtained sharing the same unit as CPO (W). We aimed to validate CPO as a marker of LV SW min under various inotropic states.

Methods: We retrospectively analysed data obtained from experimental studies of the hemodynamic impact of mild hypothermia and hyperthermia on acute heart failure. Fifty-nine anaesthetized and mechanically ventilated closed-chest Landrace pigs (68 ± 1 kg) were instrumented with Swan-Ganz and LV pressure-volume catheters. Data were obtained at body temperatures of 33.0 °C, 38.0 °C and 40.5 °C; before and after: resuscitation, myocardial infarction, endotoxemia, sevoflurane-induced myocardial depression and beta-adrenergic stimulation. We plotted LVSW min against CPO by linear regression analysis, as well as against the following classical indices of LV function and work: LV ejection fraction (LV EF), rate-pressure product (RPP), triple product (TP), LV maximum pressure (LVP) and maximal rate of rise of LVP (LV dP/dt).

Results: CPO showed the best correlation with LV SW min (r = 0.89; p < 0.05) while LV EF did not correlate at all (r = 0.01; p = 0.259). Further parameters correlated moderately with LV SW min (LVP r = 0.47, RPP r = 0.67; and TP r = 0.54). LV dP/dt correlated worst with LV SW min (r = 0.28).

Conclusion: CPO reflects external cardiac work over a wide range of inotropic states. These data further support the use of CPO to monitor inotropic interventions in the ICU.
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http://dx.doi.org/10.1186/s12872-019-1212-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6792198PMC
October 2019

Long-Term Follow-Up of Idiopathic Ventricular Fibrillation in a Pediatric Population: Clinical Characteristics, Management, and Complications.

J Am Heart Assoc 2019 05;8(9):e011172

1 Electrophysiology Department, Hopital Haut Lévêque Bordeaux France.

Background The natural history and long-term outcome in pediatric patients with idiopathic ventricular fibrillation ( IVF ) are poorly characterized. We sought to define the clinical characteristics and long-term outcomes of a pediatric cohort with an initial diagnosis of IVF . Methods and Results Patients were included from an International Registry of IVF (consisting of 496 patients). Inclusion criteria were: (1) VF with no identifiable cause following comprehensive analysis for ischemic, electrical or structural heart disease and (2) age ≤16 years. These included 54 pediatric IVF cases (age 12.7±3.7 years, 59% male) among whom 28 (52%) had a previous history of syncope (median 2 syncopal episodes [interquartile range 1]). Thirty-six (67%) had VF in situations associated with high adrenergic tone. During a median 109±12 months of follow-up, 31 patients (57%) had recurrence of ventricular arrhythmias, mainly VF . Two patients developed phenotypic expression of an inherited arrhythmia syndrome during follow-up (hypertrophic cardiomyopathy and long QT syndrome, respectively). A total of 15 patients had positive genetic testing for inherited arrhythmia syndromes. Ten patients (18%) experienced device-related complications. Three patients (6%) died, 2 due to VF storm. Conclusions In pediatric patients with IVF , a minority develop a definite clinical phenotype during long-term follow-up. Recurrent VF is common in this patient group.
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http://dx.doi.org/10.1161/JAHA.118.011172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512137PMC
May 2019

Sniff of coke breaks the heart: cocaine-induced coronary vasospasm aggravated by therapeutic hypothermia and vasopressors after aborted sudden cardiac death: a case report.

Eur Heart J Case Rep 2018 Jun 17;2(2):yty041. Epub 2018 Apr 17.

Division of Cardiology, Department of Medicine, Medical University of Graz, Auenbruggerplatz 15, Graz, Austria.

Introduction: Coronary vasospasm and sudden cardiac death are a frequently reported complication of cocaine abuse. We present a case with uniquely severe clinical and angiographic presentation.

Case Presentation: A 39-year-old patient was presented to the cath lab after out-of-hospital cardiac arrest. Coronary angiography revealed focal coronary vasospasm in the proximal LCx, well responsive for intracoronary nitrates. Accordingly, no coronary intervention was performed and the patient was transferred to the cardiac intensive care unit. There, after systematically cooling sudden haemodynamic deterioration and massive ST-elevation was observed. Repeated coronary angiography revealed subocclusive LAD and LCx vasospasm, which again recovered after intracoronary injection of nitric oxide.

Discussion: Coronary-spastic effect of cocaine and its potentially dreadful clinical consequences are well-described phenomena. As novelty this case emphasizes that standard of care, including systematic hypothermia and vasopressor administration after out-of-hospital cardiac arrest can potentiate cocaine-induced coronary spasm with dramatic outcomes.
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http://dx.doi.org/10.1093/ehjcr/yty041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6177107PMC
June 2018

Is there a difference in rhythm outcome between patients undergoing first line versus second line paroxysmal atrial fibrillation ablation?

PLoS One 2018 7;13(12):e0208994. Epub 2018 Dec 7.

Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.

Background: Catheter ablation of atrial fibrillation (AF) is an established second line therapy for patients with symptomatic paroxysmal AF (PAF) and may be considered as a first line therapy in selected patients who are highly symptomatic, considering patient choice, benefit, and risk, according to recent guidelines. Our study investigated whether a first line vs. second line ablation approach may result in improved sinus rhythm maintenance after ablation.

Methods: A total of 153 patients undergoing pulmonary vein isolation for PAF were included in the study (age 55±12 years, 29% female). Seventy-nine patients underwent first line AF ablation and 74 patients underwent second line AF ablation after failed antiarrhythmic drug therapy. There was no significant difference in baseline characteristics such as age, history of AF, left atrial size or LVEF between groups. Success was defined as atrial tachyarrhythmia free survival during a 12-month follow-up by means of serial ECG Holter monitoring.

Results: There was no significant difference in cumulative arrhythmia-free survival between those patients who received AF ablation as a first or second line therapy. Single procedure success was 78% in the first line group vs. 81% in the second line group; multiple procedure success was 90 vs. 91%, (n.s.). Complication rate was 1.3% vs. 1.4% (n.s.).

Conclusion: Success of AF ablation did not differ between patients who receive ablation as first vs. second line therapy. Based on these data, a trial of AAD therapy before AF ablation may be justified in most patients with symptomatic PAF eligible for rhythm control.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0208994PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6285381PMC
May 2019

Indications for and outcome in patients with the wearable cardioverter-defibrillator in a nurse-based training programme: results of the Austrian WCD Registry.

Eur J Cardiovasc Nurs 2019 01 1;18(1):75-83. Epub 2018 Aug 1.

1 Department of Cardiology, Medical University of Graz, Austria.

Background: The wearable cardioverter-defibrillator is a treatment option for patients at temporarily high risk of sudden cardiac death or in whom implantation of a cardioverter-defibrillator is temporarily not possible.

Objectives: The aim of this study was to provide real-world data on patients receiving this therapy in a nurse-based wearable cardioverter-defibrillator training programme.

Methods: A registry including all patients prescribed with a wearable cardioverter-defibrillator in Austria between 2010 and 2016. Overall, 448 patients received a wearable cardioverter-defibrillator in 48 centres. Patients received structured nurse-based wearable cardioverter-defibrillator educational initial training followed by remote monitoring.

Results: Main indications were: severe non-ischaemic cardiomyopathy (21%); recent myocardial infarction and percutaneous coronary intervention (20%); and stable coronary artery disease with percutaneous coronary intervention/coronary artery bypass grafting (14%). Eleven patients (2.5%) received 22 appropriate wearable cardioverter-defibrillator shocks. Two patients (0.4%) received three inappropriate shocks. The risk of sudden cardiac death varied between different aetiologies. Eight out of 11 (73%) patients received their first wearable cardioverter-defibrillator shock within 30 days. The main reasons for termination of the wearable cardioverter-defibrillator therapy were implantable cardioverter-defibrillator implantation (55.5%) and improvement of left ventricular ejection fraction to more than 35% (33%).

Conclusion: The wearable cardioverter-defibrillator is an effective and safe treatment option in patients at either transiently elevated risk of ventricular tachycardia/ventricular fibrillation or mandated postponed implantable cardioverter-defibrillator implantation, with a 2.5% shock rate over a median 54 days wearable cardioverter-defibrillator treatment period. However, both the wearable cardioverter-defibrillator shock rate and implantable cardioverter-defibrillator implantation rate vary widely depending on the wearable cardioverter-defibrillator indication. Nurse-based wearable cardioverter-defibrillator training is associated with high patient adherence, with a median wearing duration per day of 23.5 (1-24) hours.
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http://dx.doi.org/10.1177/1474515118790365DOI Listing
January 2019

Arterial hypertension drives arrhythmia progression via specific structural remodeling in a porcine model of atrial fibrillation.

Heart Rhythm 2018 09 23;15(9):1328-1336. Epub 2018 May 23.

Division of Cardiology, Department of Medicine, Medical University of Graz, Graz, Austria; Department of Cardiology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.

Background: Arterial hypertension (HT) contributes to progression of atrial fibrillation (AF) via unknown mechanisms.

Objective: We aimed to characterize electrical and structural changes accounting for increased AF stability in a large animal model of rapid atrial pacing (RAP)-induced AF combined with desoxycorticosterone acetate (DOCA)-induced HT.

Methods: Eighteen pigs were instrumented with right atrial endocardial pacemaker leads and custom-made pacemakers to induce AF by continuous RAP (600 beats/min). DOCA pellets were subcutaneously implanted in a subgroup of 9 animals (AF+HT group); the other 9 animals served as controls (AF group). Final experiments included electrophysiology studies, endocardial electroanatomic mapping, and high-density mapping with epicardial multielectrode arrays. In addition, 3-dimensional computational modeling was performed.

Results: DOCA implantation led to secondary HT (median [interquartile range] aortic pressure 109.9 [100-137] mm Hg in AF+HT vs 82.2 [79-96] mm Hg in AF; P < .05), increased AF stability (55.6% vs 12.5% of animals with AF episodes lasting >1 hour; P < .05), concentric left ventricular hypertrophy, atrial dilatation (119 ± 31 cm in AF+HT vs 78 ± 23 cm in AF; P < .05), and fibrosis. Collagen accumulation in the AF+HT group was mainly found in non-intermyocyte areas (1.62 ± 0.38 cm in AF+HT vs 0.96 ± 0.3 cm in AF; P < .05). Left and right atrial effective refractory periods, action potential durations, endo- and epicardial conduction velocities, and measures of AF complexity were comparable between the 2 groups. A 3-dimensional computational model confirmed an increase in AF stability observed in the in vivo experiments associated with increased atrial size.

Conclusion: In this model of secondary HT, higher AF stability after 2 weeks of RAP is mainly driven by atrial dilatation.
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http://dx.doi.org/10.1016/j.hrthm.2018.05.016DOI Listing
September 2018

Acute stimulation of the soluble guanylate cyclase does not impact on left ventricular capacitance in normal and hypertrophied porcine hearts in vivo.

Am J Physiol Heart Circ Physiol 2018 09 4;315(3):H669-H680. Epub 2018 May 4.

Department of Internal Medicine and Cardiology, Charité-Universitätsmedizin Berlin, Berlin , Germany.

Experimental data indicate that stimulation of the nitric oxide-soluble guanylate cyclase(sGC)-cGMP-PKG pathway can increase left ventricular (LV) capacitance via phosphorylation of the myofilamental protein titin. We aimed to test whether acute pharmacological sGC stimulation with BAY 41-8543 would increase LV capacitance via titin phosphorylation in healthy and deoxycorticosteroneacetate (DOCA)-induced hypertensive pigs. Nine healthy Landrace pigs and 7 pigs with DOCA-induced hypertension and LV concentric hypertrophy were acutely instrumented to measure LV end-diastolic pressure-volume relationships (EDPVRs) at baseline and during intravenous infusion of BAY 41-8543 (1 and 3 μg·kg·min for 30 min, respectively). Separately, in seven healthy and six DOCA pigs, transmural LV biopsies were harvested from the beating heart to measure titin phosphorylation during BAY 41-8543 infusion. LV EDPVRs before and during BAY 41-8543 infusion were superimposable in both healthy and DOCA-treated pigs, whereas mean aortic pressure decreased by 20-30 mmHg in both groups. Myocardial titin phosphorylation was unchanged in healthy pigs, but total and site-specific (Pro-Glu-Val-Lys and N2-Bus domains) titin phosphorylation was increased in DOCA-treated pigs. Bicoronary nitroglycerin infusion in healthy pigs ( n = 5) induced a rightward shift of the LV EDPVR, demonstrating the responsiveness of the pathway in this model. Acute systemic sGC stimulation with the sGC stimulator BAY 41-8543 did not recruit an LV preload reserve in both healthy and hypertrophied LV porcine myocardium, although it increased titin phosphorylation in the latter group. Thus, increased titin phosphorylation is not indicative of increased in vivo LV capacitance. NEW & NOTEWORTHY We demonstrate that acute pharmacological stimulation of soluble guanylate cyclase does not increase left ventricular compliance in normal and hypertrophied porcine hearts. Effects of long-term soluble guanylate cyclase stimulation with oral compounds in disease conditions associated with lowered myocardial cGMP levels, i.e., heart failure with preserved ejection fraction, remain to be investigated.
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http://dx.doi.org/10.1152/ajpheart.00510.2017DOI Listing
September 2018

Mild hypothermia (33°C) increases the inducibility of atrial fibrillation: An in vivo large animal model study.

Pacing Clin Electrophysiol 2018 07 15;41(7):720-726. Epub 2018 May 15.

Department of Cardiology, Medical University of Graz, Graz, Austria.

Objective: Application of therapeutic mild hypothermia in patients after resuscitation, often accompanied by myocardial infarction, cardiogenic shock, and systemic inflammation may impact on cardiac rhythm. We therefore tested susceptibility to atrial arrhythmias during hyperthermia (HT, 40.5°C), normothermia (NT, 38.0°C), and mild hypothermia (MH, 33.0°C).

Methods: Nine healthy, anesthetized closed-chest landrace pigs were instrumented with a quadripolar stimulation catheter in the high right atrium and a decapolar catheter in the coronary sinus. Twelve-lead surface electrograms were recorded and core body temperature was altered to HT, NT, and MH using external warming or intravascular cooling. Repetitive measurements of effective atrial refractory period (AERP), atrial fibrillation (AF) inducibility, and electrocardiogram (ECG) parameters at different heart rates were performed.

Results: During MH, AERP was significantly longer while the inducibility of AF was significantly higher compared to NT and HT (median [range]: HT 18 (0, 80)%; NT 25 (0, 80)%; MH 68 (0, 100)%; P < 0.05 MH vs NT+HT). Mean AF duration did not differ between groups. Arterial potassium levels decreased with falling temperatures (HT: 4.2 ± 0.1 mmol/L; NT: 4.0 ± 0.2 mmol/L; MH: 3.5 ± 0.1 mmol/L; P < 0.001). Surface ECGs during MH showed reduced spontaneous heart rate (HT: 99 ± 13 beats/min; NT: 87 ± 15 beats/min; MH: 66 ± 10 beats/min; P < 0.05), increased PQ, stim-Q, and QT intervals (P < 0.01) but no change in QRS duration or time from peak to end of the T wave interval.

Conclusion: Our data imply that MH represents an arrhythmic substrate rendering the atria more susceptible to AF although conduction times as well as refractory periods are increased. Further investigations on potential electrophysiological limits of therapeutic cooling in patients are required.
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http://dx.doi.org/10.1111/pace.13351DOI Listing
July 2018

Oversensing of the wearable cardioverter defibrillator during bipolar ventricular stimulation.

Wien Klin Wochenschr 2017 Dec 9;129(23-24):910-912. Epub 2017 Nov 9.

Division of Cardiology, Department of Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria.

The wearable cardioverter defibrillator (WCD) is a temporary treatment option for patients with potentially reversible risk of sudden cardiac death. This case demonstrates a pitfall during WCD usage in a pacemaker-dependent patient as well as a possible solution allowing continuation of WCD therapy. Bipolar stimulation may lead to double counting of the WCD detection algorithm resulting in false alarm or inappropriate therapy.
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http://dx.doi.org/10.1007/s00508-017-1290-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5711981PMC
December 2017

CHA2DS2-VASc score and blood biomarkers to identify patients with atrial high-rate episodes and paroxysmal atrial fibrillation.

Europace 2017 Apr;19(4):544-551

Department of Cardiology, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, Berlin 13353, Germany.

Aims: Paroxysmal atrial fibrillation (PAF) is often asymptomatic but nonetheless harmful. We evaluated the performance of disease-related blood biomarkers and CHA2DS2-VASc score to discriminate for PAF in patients with continuous rhythm monitoring.

Methods And Results: Clinical data and blood samples were obtained from patients with dual-chamber pacemakers selected according to the absence (no_AHRE) or presence of Atrial High-Rate Episodes (AHRE) >6 min in recent device history (case-control approach). We included 93 patients (n = 49 AHRE, n = 44 no_AHRE). In a subgroup with high AHRE burden and confirmed PAF 15 biomarkers were evaluated (n = 19 AHRE-AF vs. n = 20 no_AHRE). Significantly regulated biomarkers were then tested in all patients to distinguish no_AHRE from AHRE (receiver operating characteristics analysis). Hsp27, TGFβ1, cystatin C, matrix metalloproteinases MMP-2,-3,-9, albumin, and serum uric acid were not altered in the subgroup. Tissue inhibitors of metalloproteinases (TIMP) -1,-2,-4; NT-proANP, NT-proBNP, IL-6 and serum amyloid protein A were significantly different in AHRE vs. no_AHRE (subgroup and whole cohort), with best discriminatory performance for TIMP-4. Biomarkers performed better than CHADS2-VASc for AHRE discrimination. Intracardial electrograms and medical history from seven AHRE patients suggested atrial tachycardia and not AF (AHRE-AT). Four of the most relevant regulated biomarkers (TIMP-4, TIMP-2, SAA, NT-proBNP) behaved similarly in AHRE-AT and AHRE-AF. NT-proBNP >150 pg/mL indicated an odds ratio of 12.9 for AHRE. Combining two biomarkers significantly improved discrimination of AHRE.

Conclusion: TIMP-4, NT-proANP, NT-proBNP were strongest associated with PAF and AHRE. The discriminatory performance of CHADS2-VASc for PAF was increased by addition of selected biomarkers.
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http://dx.doi.org/10.1093/europace/euw101DOI Listing
April 2017

Atrial fibrillation in transcatheter aortic valve implantation patients: Incidence, outcome and predictors of new onset.

J Electrocardiol 2017 Jul - Aug;50(4):402-409. Epub 2017 Feb 20.

Division of Cardiology, Medical University of Graz, Graz, Austria.

Background: There is controversial evidence if atrial fibrillation (AF) alters outcome after transcatheter aortic valve implantation (TAVI). TAVI itself may promote new-onset AF (NOAF).

Methods: We performed a single-center study including 398 consecutive patients undergoing TAVI. Before TAVI, patients were divided into a sinus rhythm (SR) group (n=226, 57%) and baseline AF group (n=172, 43%) according to clinical records and electrocardiograms. Furthermore, incidence and predictors of NOAF were recorded.

Results: Baseline AF patients had a significantly higher 1-year mortality than the baseline SR group (19.8% vs. 11.5%, p=0.02). NOAF occurred in 7.1% of patients with prior SR. Previous valve surgery was the only significant predictor of NOAF (HR 5.86 [1.04-32.94], p<0.05). NOAF was associated with higher rehospitalization rate (62.5 vs. 34.8%, p=0.04), whereas mortality was unaffected.

Conclusions: This study shows that NOAF is associated with higher rates of rehospitalization but not mortality after TAVI. Overall, patients with pre-existing AF have higher mortality.
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http://dx.doi.org/10.1016/j.jelectrocard.2017.02.013DOI Listing
May 2018

Assessment of cardiac fibrosis: a morphometric method comparison for collagen quantification.

J Appl Physiol (1985) 2017 Apr 26;122(4):1019-1030. Epub 2017 Jan 26.

Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.

Fibrotic remodeling of the heart is a frequent condition linked to various diseases and cardiac dysfunction. Collagen quantification is an important objective in cardiac fibrosis research; however, a variety of different histological methods are currently used that may differ in accuracy. Here, frequently applied collagen quantification techniques were compared. A porcine model of early stage heart failure with preserved ejection fraction was used as an example. Semiautomated threshold analyses were imprecise, mainly due to inclusion of noncollagen structures or failure to detect certain collagen deposits. In contrast, collagen assessment by automated image analysis and light microscopy (LM)-stereology was more sensitive. Depending on the quantification method, the amount of estimated collagen varied and influenced intergroup comparisons. PicroSirius Red, Masson's trichrome, and Azan staining protocols yielded similar results, whereas the measured collagen area increased with increasing section thickness. Whereas none of the LM-based methods showed significant differences between the groups, electron microscopy (EM)-stereology revealed a significant collagen increase between cardiomyocytes in the experimental group, but not at other localizations. In conclusion, in contrast to the staining protocol, section thickness and the quantification method being used directly influence the estimated collagen content and thus, possibly, intergroup comparisons. EM in combination with stereology is a precise and sensitive method for collagen quantification if certain prerequisites are considered. For subtle fibrotic alterations, consideration of collagen localization may be necessary. Among LM methods, LM-stereology and automated image analysis are appropriate to quantify fibrotic changes, the latter depending on careful control of algorithm and comparable section staining. Direct comparison of frequently applied histological fibrosis assessment techniques revealed a distinct relation of measured collagen and utilized quantification method as well as section thickness. Besides electron microscopy-stereology, which was precise and sensitive, light microscopy-stereology and automated image analysis proved to be appropriate for collagen quantification. Moreover, consideration of collagen localization might be important in revealing minor fibrotic changes.
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http://dx.doi.org/10.1152/japplphysiol.00987.2016DOI Listing
April 2017

Early-stage heart failure with preserved ejection fraction in the pig: a cardiovascular magnetic resonance study.

J Cardiovasc Magn Reson 2016 Sep 30;18(1):63. Epub 2016 Sep 30.

Division of General Radiology, Department of Radiology, Medical University of Graz, Auenbruggerplatz 9/P, 8036, Graz, Austria.

Background: The hypertensive deoxy-corticosterone acetate (DOCA)-salt-treated pig (hereafter, DOCA pig) was recently introduced as large animal model for early-stage heart failure with preserved ejection fraction (HFpEF). The aim of the present study was to evaluate cardiovascular magnetic resonance (CMR) of DOCA pigs and weight-matched control pigs to characterize ventricular, atrial and myocardial structure and function of this phenotype model.

Methods: Five anesthetized DOCA and seven control pigs underwent 3 T CMR at rest and during dobutamine stress. Left ventricular/atrial (LV/LA) function and myocardial mass (LVMM), strains and torsion were evaluated from (tagged) cine imaging. 4D phase-contrast measurements were used to assess blood flow and peak velocities, including transmitral early-diastolic (E) and myocardial tissue (E') velocities and coronary sinus blood flow. Myocardial perfusion reserve was estimated from stress-to-rest time-averaged coronary sinus flow. Global native myocardial T1 times were derived from prototype modified Look-Locker inversion-recovery (MOLLI) short-axis T1 maps. After in-vivo measurements, transmural biopsies were collected for stereological evaluation including the volume fractions of interstitium (V(int/LV)) and collagen (V(coll/LV)). Rest, stress, and stress-to-rest differences of cardiac and myocardial parameters in DOCA and control animals were compared by t-test.

Results: In DOCA pigs LVMM (p < 0.001) and LV wall-thickness (end-systole/end-diastole, p = 0.003/p = 0.007) were elevated. During stress, increase of LV ejection-fraction and decrease of end-systolic volume accounted for normal contractility reserves in DOCA and control pigs. Rest-to-stress differences of cardiac index (p = 0.040) and end-diastolic volume (p = 0.042) were documented. Maximal (p = 0.042) and minimal (p = 0.012) LA volumes in DOCA pigs were elevated at rest; total LA ejection-fraction decreased during stress (p = 0.006). E' was lower in DOCA pigs, corresponding to higher E/E' at rest (p = 0.013) and stress (p = 0.026). Myocardial perfusion reserve was reduced in DOCA pigs (p = 0.031). T1-times and V(int/LV) did not differ between groups, whereas V(coll/LV) levels were higher in DOCA pigs (p = 0.044).

Conclusions: LA enlargement, E' and E/E' were the markers that showed the most pronounced differences between DOCA and control pigs at rest. Inadequate increase of myocardial perfusion reserve during stress might represent a metrics for early-stage HFpEF. Myocardial T1 mapping could not detect elevated levels of myocardial collagen in this model.

Trial Registration: The study was approved by the local Bioethics Committee of Vienna, Austria (BMWF-66.010/0091-II/3b/2013).
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5043627PMC
http://dx.doi.org/10.1186/s12968-016-0283-9DOI Listing
September 2016

A porcine model of early atrial fibrillation using a custom-built, radio transmission-controlled pacemaker.

J Electrocardiol 2016 Mar-Apr;49(2):124-31. Epub 2015 Dec 23.

Department of Internal Medicine, Medical University of Graz, Graz, Austria.

Mechanisms underlying atrial remodeling toward atrial fibrillation (AF) are incompletely understood. We induced AF in 16 pigs by 6weeks of rapid atrial pacing (RAP, 600bpm) using a custom-built, telemetrically controlled pacemaker. AF evolution was monitored three times per week telemetrically in unstressed, conscious animals. We established a dose-response relationship between RAP duration and occurrence of sustained AF >60minutes. Left atrial (LA) dilatation was present already at 2weeks of RAP. There was no evidence of left ventricular heart failure after 6weeks of RAP. As a proof-of-principle, arterial hypertension was induced in 5/16 animals by implanting desoxycorticosterone acetate (DOCA, an aldosterone-analog) subcutaneously to accelerate atrial remodeling. RAP+DOCA resulted in increased AF stability with earlier onset of sustained AF and accelerated anatomical atrial remodeling with more pronounced LA dilatation. This novel porcine model can serve to characterize effects of maladaptive stimuli or protective interventions specifically during early AF.
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http://dx.doi.org/10.1016/j.jelectrocard.2015.12.012DOI Listing
December 2016

Inotropic Effects of Experimental Hyperthermia and Hypothermia on Left Ventricular Function in Pigs-Comparison With Dobutamine.

Crit Care Med 2016 Mar;44(3):e158-67

1Department of Cardiology, Medical University of Graz, Graz, Austria.2Department of General and Interventional Cardiology, University Heart Center Hamburg-Eppendorf, Hamburg, Germany.3Department of Cardiothoracic Surgery, Medical University of Graz, Graz, Austria.4Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.5Department of Cardiology, Charité Berlin Campus Virchow, Berlin, Germany.

Objectives: The results from the recent Targeted Temperature Management trial raised the question whether cooling or merely the avoidance of fever mediates better neurologic outcome in resuscitated patients. As temperature per se is a major determinant of cardiac function, we characterized the effects of hyperthermia (40.5°C), normothermia (38.0°C), and mild hypothermia (33.0°C) on left ventricular contractile function in healthy pigs and compared them with dobutamine infusion.

Design: Animal study.

Setting: Large animal facility, Medical University of Graz, Graz, Austria.

Subjects: Nine anesthetized and mechanically ventilated closed-chest Landrace pigs (67 ± 2 kg).

Interventions: Core body temperature was controlled using an intravascular device. At each temperature step, IV dobutamine was titrated to double maximum left ventricular dP/dt (1.8 ± 0.1 µg/kg/min at normothermia). Left ventricular pressure-volume relationships were assessed during short aortic occlusions. Left ventricular contractility was assessed by the calculated left ventricular end-systolic volume at an end-systolic left ventricular pressure of 100 mm Hg.

Measurements And Main Results: Heart rate (98 ± 4 vs 89 ± 4 vs 65 ± 2 beats/min; all p < 0.05) and cardiac output (6.7 ± 0.3 vs 6.1 ± 0.3 vs 4.4 ± 0.2 L/min) decreased with cooling from hyperthermia to normothermia and mild hypothermia, whereas left ventricular contractility increased (left ventricular end-systolic volume at a pressure of 100 mm Hg: 74 ± 5 mL at hyperthermia, 52 ± 4 mL at normothermia, and 41 ± 3 mL at mild hypothermia; all p < 0.05). The effect of cooling on left ventricular end-systolic volume at a pressure of 100 mm Hg (hyperthermia to normothermia: -28% ± 3% and normothermia to mild hypothermia: -20% ± 5%) was of comparable effect size as dobutamine at a given temperature (hyperthermia: -28% ± 4%, normothermia: -27% ± 6%, and mild hypothermia: -27% ± 9%).

Conclusions: Cooling from hyperthermia to normothermia and from normothermia to mild hypothermia increased left ventricular contractility to a similar degree as a significant dose of dobutamine in the normal porcine heart. These data indicate that cooling can reduce the need for positive inotropes and that lower rather than higher temperatures are appropriate for the resuscitated failing heart.
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http://dx.doi.org/10.1097/CCM.0000000000001358DOI Listing
March 2016

A porcine model of hypertensive cardiomyopathy: implications for heart failure with preserved ejection fraction.

Am J Physiol Heart Circ Physiol 2015 Nov 4;309(9):H1407-18. Epub 2015 Sep 4.

Division of Cardiology, Medical Department, Charité Berlin Campus Virchow, Berlin, Germany

Heart failure with preserved ejection fraction (HFPEF) evolves with the accumulation of risk factors. Relevant animal models to identify potential therapeutic targets and to test novel therapies for HFPEF are missing. We induced hypertension and hyperlipidemia in landrace pigs (n = 8) by deoxycorticosteroneacetate (DOCA, 100 mg/kg, 90-day-release subcutaneous depot) and a Western diet (WD) containing high amounts of salt, fat, cholesterol, and sugar for 12 wk. Compared with weight-matched controls (n = 8), DOCA/WD-treated pigs showed left ventricular (LV) concentric hypertrophy and left atrial dilatation in the absence of significant changes in LV ejection fraction or symptoms of heart failure at rest. The LV end-diastolic pressure-volume relationship was markedly shifted leftward. During simultaneous right atrial pacing and dobutamine infusion, cardiac output reserve and LV peak inflow velocities were lower in DOCA/WD-treated pigs at higher LV end-diastolic pressures. In LV biopsies, we observed myocyte hypertrophy, a shift toward the stiffer titin isoform N2B, and reduced total titin phosphorylation. LV superoxide production was increased, in part attributable to nitric oxide synthase (NOS) uncoupling, whereas AKT and NOS isoform expression and phosphorylation were unchanged. In conclusion, we developed a large-animal model in which loss of LV capacitance was associated with a titin isoform shift and dysfunctional NOS, in the presence of preserved LV ejection fraction. Our findings identify potential targets for the treatment of HFPEF in a relevant large-animal model.
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http://dx.doi.org/10.1152/ajpheart.00542.2015DOI Listing
November 2015

In patients with persistent atrial fibrillation complex ablation techniques were no better than pulmonary vein isolation alone in preventing recurrent atrial fibrillation.

Evid Based Med 2015 Oct 12;20(5):175. Epub 2015 Aug 12.

Division of Cardiology, Medical University of Graz, Graz, Austria.

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http://dx.doi.org/10.1136/ebmed-2015-110238DOI Listing
October 2015

Length of the Mitral Isthmus But Not Anatomical Location of Ablation Line Predicts Bidirectional Mitral Isthmus Block in Patients Undergoing Catheter Ablation of Persistent Atrial Fibrillation: A Randomized Controlled Trial.

J Cardiovasc Electrophysiol 2015 Jun 29;26(6):629-34. Epub 2015 Apr 29.

Hôpital Cardiologique du Haut Lévêque, Université Victor-Segalen Bordeaux, Pessac, France.

Introduction: Mitral isthmus (MI) ablation is an effective option in patients undergoing ablation for persistent atrial fibrillation (AF). Achieving bidirectional conduction block across the MI is challenging, and predictors of MI ablation success remain incompletely understood. We sought to determine the impact of anatomical location of the ablation line on the efficacy of MI ablation.

Methods And Results: A total of 40 consecutive patients (87% male; 54 ± 10 years) undergoing stepwise AF ablation were included. MI ablation was performed in sinus rhythm. MI ablation was performed from the left inferior PV to either the posterior (group 1) or the anterolateral (group 2) mitral annulus depending on randomization. The length of the MI line (measured with the 3D mapping system) and the amplitude of the EGMs at 3 positions on the MI were measured in each patient. MI block was achieved in 14/19 (74%) patients in group 1 and 15/21 (71%) patients in group 2 (P = NS). Total MI radiofrequency time (18 ± 7 min vs. 17 ± 8 min; P = NS) was similar between groups. Patients with incomplete MI block had a longer MI length (34 ± 6 mm vs. 24 ± 5 mm; P < 0.001), a higher bipolar voltage along the MI (1.75 ± 0.74 mV vs. 1.05 ± 0.69 mV; P < 0.01), and a longer history of continuous AF (19 ± 17 months vs. 10 ± 10 months; P < 0.05). In multivariate analysis, decreased length of the MI was an independent predictor of successful MI block (OR 1.5; 95% CI 1.1-2.1; P < 0.05).

Conclusions: Increased length but not anatomical location of the MI predicts failure to achieve bidirectional MI block during ablation of persistent AF.
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http://dx.doi.org/10.1111/jce.12667DOI Listing
June 2015