Jennifer Franke

Universität Heidelberg, Heidelburg, Baden-Württemberg, Germany

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Publications (52)163.66 Total impact

  • 08/2014;
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    ABSTRACT: Aim Numerous genes are known to cause dilated cardiomyopathy (DCM). However, until now technological limitations have hindered elucidation of the contribution of all clinically relevant disease genes to DCM phenotypes in larger cohorts. We now utilized next-generation sequencing to overcome these limitations and screened all DCM disease genes in a large cohort. Methods and results In this multi-centre, multi-national study, we have enrolled 639 patients with sporadic or familial DCM. To all samples, we applied a standardized protocol for ultra-high coverage next-generation sequencing of 84 genes, leading to 99.1% coverage of the target region with at least 50-fold and a mean read depth of 2415. In this well characterized cohort, we find the highest number of known cardiomyopathy mutations in plakophilin-2, myosin-binding protein C-3, and desmoplakin. When we include yet unknown but predicted disease variants, we find titin, plakophilin-2, myosin-binding protein-C 3, desmoplakin, ryanodine receptor 2, desmocollin-2, desmoglein-2, and SCN5A variants among the most commonly mutated genes. The overlap between DCM, hypertrophic cardiomyopathy (HCM), and channelopathy causing mutations is considerably high. Of note, we find that >38% of patients have compound or combined mutations and 12.8% have three or even more mutations. When comparing patients recruited in the eight participating European countries we find remarkably little differences in mutation frequencies and affected genes. Conclusion This is to our knowledge, the first study that comprehensively investigated the genetics of DCM in a large-scale cohort and across a broad gene panel of the known DCM genes. Our results underline the high analytical quality and feasibility of Next-Generation Sequencing in clinical genetic diagnostics and provide a sound database of the genetic causes of DCM.
    European Heart Journal 08/2014; · 14.10 Impact Factor
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    ABSTRACT: To report procedural outcome of sequential occlusion of the left atrial appendage (LAA) and an interatrial septal communication and discuss possible indications.
    Journal of Interventional Cardiology 08/2014; 27(4):414-22. · 1.50 Impact Factor
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    ABSTRACT: Objectives Aim of this study was to demonstrate the feasibility, safety and short-term outcome of left atrial appendage (LAA) closure with a new generation LAA closure device.Background The Amulet device (AGA, St Jude Medical, Minneapolis, MN, USA) is a new generation of the Amplatzer Cardiac Plug (ACP), specifically designed for LAA closure. This new version is designed to facilitate the implantation process and minimize procedural or device-related complications.Methods The device was implanted in 17 patients with non-valvular atrial fibrillation (AF). Clinical data were obtained at baseline, during the procedure, at discharge, at 30 days and 90 days.ResultsAll devices were implanted successfully. Device sizes ranged from 20 mm to 31 mm. A 12 French (Fr) or 14 Fr delivery sheath was used depending on the selected device size. Full and partial recapture was performed in 1 case and 3 cases respectively. There was 1 procedure-related pericardial effusion successfully managed with pericardiocentesis. There was no device embolization. The mean length of stay was 2.1 ± 0.3 days. At 90 days, there were no deaths, strokes, systemic thromboembolism or bleeding complications. There was no device-related thrombus or pericardial effusion at 90-day TEE. In 2 of the 17 patients minimal peri-device flow (smaller than 2mm) was present.Conclusions The Amulet device, which has new novel features as compared with the first generation ACP, is a feasible option for LAA closure. From our initial experience, implantation of the Amulet is associated with high success rate and good short-term outcome. © 2014 Wiley Periodicals, Inc.
    Catheterization and Cardiovascular Interventions 08/2014; · 2.51 Impact Factor
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    ABSTRACT: Aims: To assess the use of proximal protection devices in consecutive patients as the preferred means of cerebral embolic protection for primary carotid stenting. Methods and results: This was a prospective single-centre study to evaluate the technical and clinical success of proximal protection devices as the first choice for embolic protection in symptomatic (≥50%) and asymptomatic (≥70%) carotid stenosis. Proximal protection devices were used for embolic protection in 124 consecutive patients. No patients were excluded for anatomical reasons. The GORE® Flow Reversal System (W.L. Gore, Flagstaff, AZ, USA) was used in 92 patients, and the Mo.Ma Ultra device (Medtronic, Minneapolis, MN, USA) in 32 patients. Follow-up duration was 30 days. Mean age was 71±8 years. Seventy-five percent of patients were male (n=93). Twenty-six of 124 (21%) treated stenoses were symptomatic. Technical success was achieved in 122 of 124 cases (98%). Due to anatomical conditions, in two patients flow reversal could not be established. In both cases additional distal filter devices were used. Carotid stenting was successful in 124 lesions (100%). Ten patients (8.1%) had contraindications to flow reversal (three high-grade ostial stenoses of the external carotid artery, seven contralateral occlusions of the internal carotid artery) in none of whom complications occurred. There were no procedural neurologic events. Within 30 days of follow-up, one patient had an ischaemic stroke (on day 11). Conclusions: Proximal protection is a safe method as the first choice for embolic protection. It can be used with a high rate of technical success.
    07/2014;
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    ABSTRACT: The 6-minute walk test (6WT) is an established tool in the assessment of endurance and prognosis in patients with chronic heart failure (CHF). For these patients there is very limited data on biological variation of 6WT distances. We determined the minimal important difference (MID) for the 6WT in patients with stable systolic CHF.
    International journal of cardiology. 07/2014;
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    ABSTRACT: Background: Patent foramen ovale (PFO) are associated with cryptogenic strokes and transient ischemic attacks (TIAs). This study examined the initial experience with a new PFO occluder, the Nit-Occlud® PFO Occlusion Device (pfm medical ag, Germany). Methods: 63 patients with history of cryptogenic stroke or transient ischemic attack and PFO underwent percutaneous closure of the defect with the Nit-Occlud® PFO Occlusion Device. The primary endpoint was successful implantation without recurrent event, device malfunction, embolization or the need for a replacement device over 6±2 weeks. All patients underwent transesophageal echocardiography (TEE) at 6-weeks, and 42 patients had repeat TEE at 6-months. Clinical follow-up at 18.7 ± 7.4 months was also performed. Results: The device was successfully implanted in 62 (98.4%) patients with no relevant procedural complications. At 6-week follow-up, 60 (95.2%) patients met the primary endpoint. A residual shunt at rest and with Valsalva was noted in 8 (12.7%) and 31 (49.2%) patients respectively at 6-week TEE. At 6-months, one of 42 (2.4%) and 9 of 42 (21.4%) patients had a residual shunt at rest and with Valsava, respectively. At 18 months, 5/63 patients had recurrent events (3 TIAs, 2 strokes). No device-related complications occurred. One patient developed atrial fibrillation. Conclusion: In patients with cryptogenic stroke or transient ischemic attack and a PFO, the Nit-Occlud® PFO Occlusion Device appears to be both a safe and effective means to occlude the PFO. It is associated with high procedural success and favorable rates of complete closure. © 2014 Wiley Periodicals, Inc.
    Catheterization and Cardiovascular Interventions 06/2014; · 2.51 Impact Factor
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    ABSTRACT: This analysis from the German Mitral Valve Registry investigates the impact of the learning curve with the MitraClip(®) technique on procedural success and complications.
    Clinical research in cardiology : official journal of the German Cardiac Society. 06/2014;
  • EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 03/2014; 9(11):1359-63. · 3.17 Impact Factor
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    ABSTRACT: Objective: To evaluate in-hospital and short-term outcomes of percutaneous mitral valve repair according to patients' logistic EuroSCORE (logEuroSCORE) in a multicenter registry.Background: The logEuroSCORE is an established tool to predict the risk of mortality during cardiac surgery. In high-risk patients percutaneous mitral valve repair with the MitraClip system represents a less-invasive alternative.Methods: Data from 1002 patients, who underwent percutaneous mitral valve repair with the MitraClip system, were analyzed in the German Transcatheter Mitral Valve Interventions (TRAMI) Registry. A logEuroSCORE (mortality risk in %) ≥ 20 was considered high risk.Results: Of all patients, 557 (55.6%) had a logEuroSCORE ≥ 20. Implantation of the MitraClip was successful in 95.5 % (942/986) patients. Moderate residual mitral valve regurgitation was more often detected in patients with a logEuroSCORE ≥ 20 (23.8% vs. 17.1% respectively, p<0.05). In patients with a logEuroSCORE ≥ 20 the procedural complication rate was 8.9% (vs. 6.4, n.s.) and the in-hospital MACCE rate 4.9% (vs. 1.4% p<0.01). The in-hospital mortality rate in patients with a logEuroSCORE ≥ 20 and logEuroSCORE < 20 was 4.3% and 1.1%, respectively (p = <0.01).Conclusion: Percutaneous mitral valve repair with the MitraClip system is feasible in patients with a logEuroSCORE ≥ 20 with similar procedural results compared to patients with lower predicted risk. Although mortality was four times higher than in patients with logEuroSCORE < 20, mortality in high risk patients was lower than predicted. In those with a logEuroSCORE ≥ 20, moderate residual mitral valve regurgitation was more frequent. © 2014 Wiley Periodicals, Inc.
    Catheterization and Cardiovascular Interventions 03/2014; · 2.51 Impact Factor
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    ABSTRACT: Patent foramen ovale (PFO) is a common anatomical variant occurring in 20-25% of the population. In most cases, a PFO remains asymptomatic. However it allows for any venous particle such as thrombus, air or vasoactive substances to bypass the lung and enter the arterial circulation. Accordingly, PFO's have been linked to cryptogenic stroke, migraine and decompression illness. While the number of device closures have been increasing the therapy remains controversial as ‑ until recently ‑ data supporting PFO closure came from non randomized studies only. In this review we will discuss the existing data on PFO closure including results of the three randomized controlled trials comparing device closure with medical therapy in patients with cryptogenic stroke. We will also focus on the implantation technique, the complications and the different devices that are used for this procedure.
    Minerva cardioangiologica. 02/2014; 62(1):83-97.
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    ABSTRACT: Objective: To evaluate the safety of percutaneous left atrial appendage (LAA) closure with the Amplatzer Cardiac Plug (ACP) in patients with non-valvular atrial fibrillation (AF) who are not eligible for oral anticoagulation with warfarin. Background: Anticoagulation is the treatment of choice for prevention of strokes in patients with AF, but some patients have contraindications to anticoagulation. Methods: A total of 60 patients with a CHA2 DS2 -VASc score of at least 1 and contraindications to warfarin who underwent percutaneous LAA closure with the ACP were included. Stroke risk assessment was performed with the CHADS2 and CHA2 DS2 -VASc score and the bleeding risk was calculated with the HAS-BLED-score. Follow-up included office visits, telephone inquiries and mail contact. Results: Mean CHADS2 -, CHA2 DS2 -VASc- and HAS-BLED scores were 2.6 (± 1.4), 4.3 (± 1.7) and 3.3 (± 1.0), respectively. Twenty-five percent had a history of previous bleeding without oral anticoagulation and 63.3 % while receiving oral anticoagulation. In 36.7 % other contraindications to warfarin were present. Procedural success was achieved in 95 %. Mean follow-up time was 1.8 (1.0-2.8) years. The estimated annual stroke risk based on the CHADS2 -score was 5.8%. The estimated annual bleeding risk on warfarin based on the HAS-BLED score was 3.7%. During follow-up, the annual incidence of stroke was 0 %. Major bleeding complications occurred in 1.9 % annually. Conclusion: Percutaneous LAA closure with the ACP in patients with contraindications to oral anticoagulation is safe. The stroke and bleeding risk after percutaneous LAA closure is lower than predicted by conventional risk scores. © 2013 Wiley Periodicals, Inc.
    Catheterization and Cardiovascular Interventions 12/2013; · 2.51 Impact Factor
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    ABSTRACT: Objectives: To determine the procedural safety, safety, and efficacy of left atrial appendage (LAA) occlusion in octogenarians. Background: Elderly patients with atrial fibrillation (AF) often do not receive appropriate anticoagulation. LAA occlusion is an option for patients with atrial fibrillation and contraindications to anticoagulation. Little is known about the procedural safety and clinical efficacy of LAA occlusion in the very elderly. Methods: A retrospective review of LAA cases at our institution between 2002 and 2013 in patients 80 years of age or older was performed. Demographic, echocardiographic, procedural, and clinical follow-up data was collected. Results: 75 cases were attempted in patients 80 years of age or older (average age 83.4 ±2.8 years, 53.3% male). Hypertension, coronary artery disease, and heart failure were present in 96%, 41.3%, and 36%, respectively. Mean CHADS2 and CHA2DS-VASc scores were 3.3 and 5.2. Devices used included the WATCHMAN, ACP, PLAATO, Lariat and Coherex devices, which were attempted in 34.7, 36, 17.3, 5.3, and 5.3 percent, respectively. Overall procedural success, safety endpoint, and one-year device efficacy was 90.1%, 3.9%, and 97.4%, respectively. Conclusions: LAA closure is a safe and efficacious method of stroke prevention in the very elderly with atrial fibrillation. © 2013 Wiley Periodicals, Inc.
    Catheterization and Cardiovascular Interventions 11/2013; · 2.51 Impact Factor
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    ABSTRACT: Though carotid artery stenting (CS) has gained popularity as an alternative to carotid endarterectomy, studies examining long-term results are limited. All consecutive patients who underwent unilateral CS between 7/1993 and 8/2005 with no or non-significant contralateral stenosis were included. Follow-up with duplex sonography and/or angiography and neurological assessment was performed at 6 and/or 12 months. Thereafter, annually, a questionnaire was sent to the patients and their referring physicians. Two-hundred and seventy-nine patients underwent CS. In 99% of procedures stent delivery was successful. The periprocedural major and minor stroke rates were 2.2%, respectively. The periprocedural major stroke or death rate was 2.9%. Median clinical follow-up was 49 ± 32 months (range: 30 days-12.1 years). Excluding perioperative (<30 days) events, the annual major and minor stroke rate was 1.3% and the annual ipsilateral major and minor stroke rate was 0.6%. In symptomatic and asymptomatic patients, the annual major and minor stroke rates were 2.2% and 0.8%, respectively, and the ipsilateral major and minor stroke rates were 1.1% and 0.3%, respectively. There was no significant difference between ipsilateral and contralateral major or minor strokes at long-term follow-up. At last sonographic follow-up (median 36 ± 32 months), restenosis rates for symptomatic and asymptomatic stenoses were 5% and 3%, respectively. The results of our study demonstrate very low long-term cerebral event rates after CS supporting the long-term safety of CS. Importantly, there was no significant difference in long-term ipsilateral versus contralateral cerebral events lending support to the hypothesis of plaque stabilization.
    Journal of Interventional Cardiology 11/2013; · 1.50 Impact Factor
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    ABSTRACT: Background: Catheter-based renal sympathetic denervation (RD) causes significant blood pressure (BP) reductions in patients with resistant hypertension (rHTN). However, hypertensive elderly patients reportedly have a lower sympathetic tone than younger patients and a blood pressure lowering effect of RD in this population has not yet been demonstrated. The purpose of this study was to assess the efficacy and safety of RD in elderly patients. Methods: We reviewed all consecutive patients aged ≥ 75 years (mean: 78 years) with rHTN treated with RD. Twenty-four patients were included in this prospective study. Office and ambulatory BPs were assessed at baseline and 6 months follow-up. Primary endpoint was the change in office systolic BP at 6 months. Results: Baseline mean office BP was 173/86 +/- 21/13 mmHg. Baseline 24-hour mean ambulatory BP, available in 22 patients, was 158/80 +/- 20/13 mmHg. Baseline creatinine was 1.0 +/- 0.18 mg/dl and mean number of antihypertensive agents at baseline 4.3 +/- 1.4. No device- or procedure-related adverse events occurred. At 6 months follow-up, the mean office BP decreased by 19/11 +/- 29/16 mmHg (p< 0.01 compared to baseline). Mean systolic 24h ambulatory BP, available in 17 patients, decreased by 9/5 +/- 13/13 mmHg. Antihypertensive medications could be reduced in 9 patients. Furthermore, renal function was not impaired. Conclusion: According to our findings, a similar magnitude of blood pressure reduction as reported in previous trials can be expected in elderly patients. Elderly patients with resistant hypertension should not be excluded from renal denervation. © 2013 Wiley Periodicals, Inc.
    Catheterization and Cardiovascular Interventions 08/2013; · 2.51 Impact Factor
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    ABSTRACT: Following promising preclinical studies we report our first clinical experience with transcatheter closure of an atrial septal defect of sinus venosus type in a 65 year old patient using the Immediate Release Patch. © 2013 Wiley Periodicals, Inc.
    Catheterization and Cardiovascular Interventions 08/2013; · 2.51 Impact Factor
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    ABSTRACT: Introduction: Paravalvular leak (PVL) after percutaneous transcatheter aortic valve replacement (TAVR) is associated with significant morbidity and mortality. Percutaneous PVL closure has been reported for balloon-expandable valves but not self-expandable valves. Methods: We conducted a review of cases at our center where patients who received TAVR with self-expandable valves and went on to develop severe PVL underwent percutaneous closure. Baseline demographic, TAVR procedural, PVL procedural, and follow-up data was collected. Results: A total of five patients with severe PVL after TAVR with a self-expanding valve underwent percutaneous PVL closure.. Four of five patients had a trial of balloon postdilatation after valve deployment and had significant persistent PVL. In all five patients, PVL went from moderate-severe to mild-moderate PVL. There were no adverse events. Conclusion: Percutaneous PVL closure for severe PVL self-expanding valve for TAVR is a safe and efficacious procedure. Procedural technique involves transesophageal guidance, a high approach through the valve struts, deployment of an appropriate size device, and careful monitoring. This method may be part of the algorithm for severe PVL after TAVR. © 2013 Wiley Periodicals, Inc.
    Catheterization and Cardiovascular Interventions 08/2013; · 2.51 Impact Factor
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    ABSTRACT: Though distal filter protection during carotid stenting reduces the risk of cerebrovascular events, periprocedural stroke remains a risk despite their broad usage. This observation may be related to the pore size of common filters. The FiberNet distal filter system is unique by its very small pore size (40 micrometers) as well as its low profile and flexibility. Little data is available regarding the clinical performance and safety of this device. The aim was the evaluation of the safety of the Fibernet Embolic Protection System during carotid artery stenting. All consecutive patients treated with carotid stenting at our institution using the FiberNet device were systematically followed. Primary endpoint was the rate of all death and stroke within 30 days of the procedure. Carotid artery stenting using the Fibernet embolic protection system was performed in 54 patients. The procedure was technical successful in all patients. Three patients (5.5%) had a TIA. Amauosis fugax occurred in two patients (3.7%). One patient (1.9%) had a minor stroke with hemiparesis of the left arm and face which resolved completely within 48 hours after the procedure. No patient died or suffered a major stroke. The safety and feasibility of the Fibernet distal protection system appears to be at least equivalent to that reported in studies using conventional distal filter protection. © 2013 Wiley Periodicals, Inc.
    Catheterization and Cardiovascular Interventions 07/2013; · 2.51 Impact Factor
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    ABSTRACT: Dilated cardiomyopathy (DCM) is one of the leading causes for cardiac transplantations and accounts for up to one-third of all heart failure cases. Since extrinsic and monogenic causes explain only a fraction of all cases, common genetic variants are suspected to contribute to the pathogenesis of DCM, its age of onset, and clinical progression. By a large-scale case-control genome-wide association study we aimed here to identify novel genetic risk loci for DCM. Applying a three-staged study design, we analysed more than 4100 DCM cases and 7600 controls. We identified and successfully replicated multiple single nucleotide polymorphism on chromosome 6p21. In the combined analysis, the most significant association signal was obtained for rs9262636 (P = 4.90 × 10(-9)) located in HCG22, which could again be replicated in an independent cohort. Taking advantage of expression quantitative trait loci (eQTL) as molecular phenotypes, we identified rs9262636 as an eQTL for several closely located genes encoding class I and class II major histocompatibility complex heavy chain receptors. The present study reveals a novel genetic susceptibility locus that clearly underlines the role of genetically driven, inflammatory processes in the pathogenesis of idiopathic DCM.
    European Heart Journal 07/2013; · 14.10 Impact Factor
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    ABSTRACT: Percutaneous patent foramen ovale (PFO) closure for secondary stroke prevention is discussed controversially. Long-term data comparing different closure devices are limited. The objective is the prospective comparison of procedural complications and long-term results after PFO closure in patients with cryptogenic stroke randomized to three different closure devices. Between January 2001 and December 2004, 660 patients with cryptogenic stroke were randomized to three different closure devices (Amplatzer, CardioSEAL-STARflex, and Helex occluder, 220 patients per group). The primary endpoint was defined as recurrent cerebral ischaemia [stroke, transient ischaemic attacks (TIA), or Amaurosis fugax], death from neurological cause, or any other paradoxical embolism within 5 years after the index procedure.Device implantation was technically successful in all interventions (n = 660; 100%). The procedure was complicated by pericardial tamponade requiring surgery in one patient (Amplatzer group) and device embolization in three patients (all Helex group). Thrombus formation on the device was detected in 12 cases (11 CardioSEALSTARflex, 1 Helex, 0 Amplatzer; P < 0.0001), of which 2 required surgery. Complete closure after single device implantation was more common with the Amplatzer and with the CardioSEAL-STARflex than with the Helex occluder: Amplatzer vs. Helex vs. CardioSEAL-STARflex: n = 217 (98.6%) vs. n = 202 (91.8%) vs. n = 213 (96.8%; P = 0.0012). Within 5 years of follow-up, the primary endpoint occurred in 25 patients (3.8%; 10 TIAs, 12 strokes and 3 cases of cerebral death). Compared with the CardioSEAL-STARflex (6%; 6 TIAs, 6 strokes, 1 cerebral death) and Helex groups (4%; 4 TIAs, 4 stroke, 1 cerebral death), significantly fewer events (P = 0.04) occurred in the Amplatzer group (1.4%; 2 strokes, 1 cerebral death). Although procedural complications and long-term neurological event rates are low regardless of the device used, the recurrent neurological event rate was significantly lower after Amplatzer than after CardioSEAL-STARflex or Helex implantation. This has important implications regarding the interpretation of trials comparing PFO closure with medical management.
    European Heart Journal 07/2013; · 14.10 Impact Factor

Publication Stats

151 Citations
163.66 Total Impact Points

Institutions

  • 2011–2014
    • Universität Heidelberg
      • Department of Cardiology
      Heidelburg, Baden-Württemberg, Germany
  • 2009–2014
    • CardioVasculäres Centrum Frankfurt
      Frankfurt, Hesse, Germany
  • 2012
    • University Hospital Frankfurt
      Frankfurt, Hesse, Germany