Henrik Fox

Herz- und Diabeteszentrum Nordrhein-Westfalen | HDZ NRW · Heart Failure Department, Heart and Diabetes Centre North Rhine-Westphalia

Sleep‐disordered breathing is common in patients with coronary artery disease undergoing coronary artery bypass grafting. Sleep‐disordered breathing is associated with increased perioperative morbidity, arrhythmias (e.g. atrial fibrillation) and mortality. This study investigated the impact of sleep‐disordered breathing on the postoperative course...

Right heart failure (RHF) is associated with poor outcomes, especially in patients undergoing left ventricular assist device (LVAD) implantation. The aim of this study was to identify predictors of RHF after LVAD implantation. Of 129 consecutive patients (mean age 56 ± 11 years, 89% male) undergoing LVAD implantation, 34 developed RHF. Compared to...

Background: After acute myocardial infarction (AMI), inflammatory processes promote tissue remodeling at the infarct site. Procollagen III amino-terminal propeptide (PIIINP) is a circulating biomarker of type III collagen synthesis that has been shown to be associated with changes in left ventricular ejection fraction (LVEF) and predicts the occurr...

The treatment of patients with terminal heart failure (HF) with a left ventricular assist device (LVAD) has been offered at the Heart and Diabetes Center North Rhine-Westphalia, Bad Oeynhausen (HDZ NRW) since 1989 to patients with end-stage HF as an alternative or to bridge the interval until a heart transplantation. Permanent VAD therapy for patie...

Cardiac resynchronisation therapy (CRT) is an established treatment for patients with symptomatic heart failure with reduced left ventricular ejection fraction (LVEF ≤ 35%; HFrEF) and conduction disturbances (QRS duration ≥ 130 ms). The presence of mechanical dyssynchrony (MD) on echocardiography has been hypothesised to be of predictive value in d...

Sleep-disordered breathing is highly prevalent in patients with heart failure and is related to increased mortality and morbidity. The gold standard for sleep diagnostic is polysomnography in a sleep laboratory. Measurement of peripheral arterial tone with a wrist-worn diagnostic device is a promising method to detect sleep-disordered breathing wit...

Background: The role of catheter ablation in patients with symptomatic atrial fibrillation and end-stage heart failure is unknown. Methods: We conducted a single-center, open-label trial in Germany that involved patients with symptomatic atrial fibrillation and end-stage heart failure who were referred for heart transplantation evaluation. Patie...

Background The out-of-hospital cardiac arrest (OHCA) in the young may be associated with a genetic predisposition which is relevant even for genetic counseling of relatives. The identification of genetic variants depends on the availability of intact genomic DNA. DNA from autopsy may be not available due to low autopsy frequencies or not suitable f...

The telemonitoring of heart failure (HF) patients is becoming increasingly important. This study aimed to evaluate the benefit of telemonitoring in end-stage HF patients with a ventricular-assistance device (VAD). A total of 26 HF-patients (66 ± 11 years, 88% male) on VAD therapy with an implantable cardioverter-defibrillator (ICD) or a cardiac res...

Objectives: This study evaluates the impact of transcatheter tricuspid valve interventions (TTVI) on cognitive function (CF), quality of life (QOL), and exercise capacity in late-stage heart failure with preserved ejection fraction (HFpEF) and relevant tricuspid regurgitation (TR). Background: Reduced cardiac output (CO) critically affects CF. S...

Introduction: Hemodynamic assessment is crucial after heart transplantation (HTX) or left ventricular assist device (LVAD) implantation. Gold-standard is invasive assessment via thermodilution (TD). Noninvasive pulse contour analysis (NPCA) is a new technology that is supposed to determine hemodynamics completely noninvasive. We aimed to validate...

Cardiac decompensation is associated with worse prognosis in patients with heart failure. Reliable methods to predict cardiac decompensation events are not yet available. Sleep-disordered breathing (SDB) is a frequent comorbidity in heart failure, and it has been shown to correlate with heart failure severity. This prospective observational trial i...

Background Cardiac resynchronization therapy (CRT) is an established therapy in patients with symptomatic heart failure with reduced left ventricular ejection fraction (LVEF <35%) (HFrEF) that have conduction disturbances as measured by prolonged QRS duration of >130 ms. Mechanical dyssynchrony (MD) in echocardiography has not proven benefit to det...

Background: Prehabilitation is gaining increasing interest and shows promising effects on short- and long-term outcomes among patients undergoing major surgery. The effect of multimodal, interdisciplinary prehabilitation has not yet been studied in patients with severe heart failure scheduled for the implantation of a left-ventricular assist device...

Background Central sleep apnea (CSA) is a disorder defined by lack of respiratory drive from the brain stem on breathing efforts. There is a lack of established therapies for CSA and most available therapies are limited by poor patient adherence, limited randomized controlled studies, and potentially adverse cardiovascular effects. The remedē Syste...

Pathogenic variants in genes that cause dilated cardiomyopathy (DCM) and arrhythmogenic cardiomyopathy (ACM) convey high risks for the development of heart failure through unknown mechanisms. Using single-nucleus RNA sequencing, we characterized the transcriptome of 880,000 nuclei from 18 control and 61 failing, nonischemic human hearts with pathog...

Background: Sleep-disordered breathing (SDB) is a highly common comorbidity in patients with heart failure (HF), and a known risk factor for ventricular tachycardia (VT) development. However, little is known about the impact of SDB treatment on VT burden in HF patients to date. Therefore, this study investigated VT burden, as well as implantable c...

Aims: Interventional transcatheter edge-to-edge mitral valve repair (TMVR) is an established treatment option for patients with severe mitral regurgitation (MR) and high operative risk. Cognitive impairment is one of the most common conditions among often extensive comorbidities in these patients. The specific patterns of cognitive decline and par...

The interactions and hemodynamic impact of transcatheter percutaneous mitral valve repair (TMR) have not yet been investigated in patients undergoing left ventricular assist device (LVAD) implantation, but hemodynamic adverse effects are feared in the combination of TMR and LVAD for altered mitral valve flow. This study investigated the hemodynamic...

Aims: The present study aims to evaluate magnetic-resonance-imaging (MRI)-assessed left atrial strain (LAS) and left atrial strain rate (LASR) as potential parameters for the diagnosis of cardiac amyloidosis (CA), the distinction of clinical subtypes and differentiation from other cardiomyopathies. Methods and results: LAS and LASR were assessed by...

Introduction Data on catheter ablation of ventricular arrhythmias (VA) are scarce in patients with left ventricular assist devices (LVADs) and current evidence predominantly consists of case reports with outdated LVAD. This prospective observational study reports our experience in terms of catheter ablation of VAs in patients with novel 3 rd genera...

We report a case of severe outflow graft infection following left ventricular assist device (LVAD) implantation. A 51-year old male LVAD patient was readmitted to our hospital presenting signs of systemic infection. One year previously, LVAD implantation (HeartMate3, Abbott, Chicago, IL, USA) with concomitant patent foramen ovale closure had been p...

Zusammenfassung Schlafbezogene Atmungsstörungen (SBAS) stellen ein gesundheitliches Risiko dar; sie beeinflussen Lebensqualität und Prognose negativ. Besonders gefährdet sind dabei angiologische Patienten mit kardiovaskulären Begleiterkrankungen wie arterielle Hypertonie, Herzinsuffizienz oder Vorhofflimmern. Dies zum einen, da die Diagnostik wegen...

OBJECTIVES Pump thrombosis remains a major challenge in heart failure patients with left ventricular HeartWare assist device. Current International Society for Heart and Lung Transplantation recommendations favour surgical pump exchange over lysis because safety and efficacy of lysis has been controversially reported. This study summarizes our expe...

Objectives: The aim of this study was to analyze our 10-year experience with the HVAD in a real-world scenario in a high-volume German heart center. Methods: We retrospectively analyzed outcomes of adults (≥18 years) with terminal heart failure (HF), who underwent HVAD implantation for durable LVAD therapy in our center between October 2009 and...

Aims: Some risk assessment tools have been developed to categorize mortality risk in heart transplant recipients, but it is unclear whether these tools can be used interchangeable in different transplant regions. Methods and results: We performed a retrospective single-centre study in 1049 adult German heart transplant recipients under jurisdict...

Various novelties have emerged since the last update of the position paper on sleep medicine in cardiology of the German Cardiac Society in 2014, which is why this revision became necessary. This new version not only includes all new studies available up to the date of printing, including references, updates on pathophysiology, diagnostics, and tre...

OBJECTIVES Patients in cardiogenic shock supported with venoarterial extracorporeal membrane oxygenation (VA-ECMO) may experience severe complications from reduced left ventricular (LV) unloading and increased cardiac afterload. These effects are usually modified by adding a percutaneous direct Impella vent or surgical LV vent on top of VA-ECMO in...

OBJECTIVES Recent data suggested that off-pump coronary artery bypass (OPCAB) may carry a higher risk for mortality in the long term when compared to on-pump coronary artery bypass (ONCAB). We, therefore, compared long-term survival and morbidity in patients undergoing ONCAB versus OPCAB in a large single-centre cohort. METHODS A total of 8981 pat...

Background Genetics of sudden cardiac deaths (SCD) remains frequently undetected. Genetic analysis is recommended in undefined selected cases in the 2021 ERC-guideline. The emergency medical service and physicians (EMS) may play a pivotal role for unraveling SCD by saving biomaterial for later molecular autopsy. Since for high-throughput DNA-sequen...

Biventricular heart failure remains a major challenge and total artificial heart (TAH) (SynCardia Systems Inc., Tucson, AZ, USA) bear hurdles, in particular in long-term application. Ventricular membrane rupture of a TAH is a feared complication and often implies a fatal outcome. Hereby we present the first case of successful and effective replacem...

Thrombus formation and thromboembolic events play important roles in various cardiovascular pathologies. The key receptor involved in platelet aggregation is the fibrinogen receptor glycoprotein IIb/IIIa. [18F]GP1, a derivative of the GPIIb/IIIa antagonist elarofiban, is a specific 18F-labeled small-molecule radiotracer that binds with high affinit...

Background Moderate-to-severe obstructive sleep apnea (OSA) is highly prevalent in heart failure patients with reduced left ventricular ejection fraction (HFrEF), and is associated with worsening cardiac function and increased mortality.Objectives The automatic positive airway pressure (APAP) trial tested the impact of APAP treatment on changes for...

A major cause of heart failure is cardiomyopathies, with dilated cardiomyopathy (DCM) as the most common form. Over 40 genes are linked to DCM, among them TTN and RBM20. Next Generation Sequencing in clinical DCM cohorts revealed truncating variants in TTN (TTNtv), accounting for up to 25% of familial DCM cases. Mutations in the cardiac splicing fa...

Obstructive sleep apnea (OSA) is an under-recognized yet highly prevalent disease that has major implications to cardiovascular health. Pulmonary hypertension (PH) is less common but none the less a fatal condition. The association of OSA and PH is a known but not well understood phenomenon. Furthermore, the relationship appears to be bi-directiona...

Background Despite substantial technical improvements in long-term mechanical circulatory support, ventricular tachycardia (VT) remains a major challenge in left ventricular assist device (LVAD) patients. Recurrent VTs in LVAD patients are not only associated with limited quality of life, but also increased mortality. Although LVAD therapy improves...

Funding Acknowledgements Type of funding sources: None. Introduction Left ventricular assist device (LVAD) is an expanding therapy in end-stage heart failure today. Although LVAD therapy bears the potential to normalize cardiac output, a majority of patients show a severely impaired physical condition at the time of LVAD implantation. To date, no...

Background: Sleep disordered breathing (SDB) is a frequent comorbidity in cardiac disease patients. Nevertheless, the prevalence and relationship between SDB and severe primary mitral regurgitation (PMR) has not been well investigated to date. Methods: A cohort of 121 patients with significant PMR undergoing mitral valve surgery were prospective...

Background The remedē System Pivotal Trial was a prospective, multi-center, randomized trial demonstrating transvenous phrenic nerve stimulation (TPNS) therapy is safe and effectively treats central sleep apnea (CSA) and improves sleep architecture and daytime sleepiness. Subsequently, the remedē System was approved by FDA in 2017. As a condition o...

Nocturnal hypoxemic burden is established as a robust prognostic metric of sleep-disordered breathing (SDB) to predict mortality and treating hypoxemic burden may improve prognosis. The aim of this study was to evaluate improvements in nocturnal hypoxemic burden using transvenous phrenic nerve stimulation (TPNS) to treat patients with central sleep...

The risk of left ventricular (LV) and right ventricular (RV) maladaptation after surgery for isolated primary mitral regurgitation (PMR) is poorly defined. We aimed to evaluate LV and RV contractile function using speckle-tracking analysis alongside with quantification of exercise tolerance in patients with PMR after mitral valve surgery. All conse...

Background Respiratory dyssynchrony (RD) is a phenomenon that may be reflected by reduced breathing efficiency (CO2 output relative to minute ventilation, V̇E/V̇CO2 slope) or by Exercise oscillatory ventilation (EOV). Low breathing efficiency and EOV indicate a worse prognosis in chronic heart failure patients with reduced ejection fraction (HFrEF)...

With great interest we read the recent article by Samhouri et al, 1 published in a recent issue of the Journal of Clinical Sleep Medicine, and we congratulate the authors on their effort to further shed light into the relationship between sleep apnea and pulmonary hypertension (PH). This is an important field, and the connection of both diseases ha...

Aim The purpose of the study was to investigate the outcome of secondary surgical aortic valve replacement (sSAVR) in patients with severe aortic regurgitation (AR) in the context of ventricular assist device (VAD) therapy. Methods From 2009 to 2020, 792 patients underwent cf‐LVAD implantation [HVAD (Medtronic, USA), n=585, and HM 3 (Abbott, USA),...

Background: Central sleep apnea (CSA) is a common comorbidity in patients with heart failure (HF) and has been linked to increased morbidity and mortality risk. In addition, CSA is associated with impaired quality of life, reduced physical performance capacity, and hypoxemia. Phrenic nerve stimulation (PNS) is a novel approach to the treatment of...

OBJECTIVES Myocardial recovery is a rare phenomenon in left ventricular assist device (LVAD) therapy. Surgical LVAD removal is associated with the risk of cardiac failure, and the individual evaluation of sufficient myocardial recovery is crucial. Thus, complete device explantation is not consistently performed to minimize perioperative risk. Howev...

Treatment of refractory cardiogenic shock has poor outcome. Levosimendan addition may help to achieve hemodynamic stabilization and improve conditions to where further treatment options such as listing for heart transplantation may become possible.

Background Redictors of repetitive left-ventricular assist device (LVAD)-thrombosis have not been studied yet. Methods We identified predictors of recurrent LVAD thrombosis in HeartWare (HVAD) patients in a long-term study from 2010 until 2020. We included all patients with two or more thrombolysis treatments for repetitive HVAD thrombosis and eff...

Background: Radiofrequency (RF) linear ablation at the left atrial (LA) roof and bottom to isolate the LA posterior wall using contiguous and optimized RF lesions was evaluated. Achieving isolation of the LA posterior wall is challenging as two continuous linear lesion sets are necessary. Methods: Forty consecutive patients with symptomatic atri...

Aims Timely referrals for transplantation and left ventricular assist device (LVAD) play a key role in favourable outcomes in patients with advanced heart failure (HF). The purpose of the Catheter Ablation for atrial fibrillation in patientS with end‐sTage heart faiLure and Eligibility for Heart Transplantation (CASTLE‐HTx) trial is to test the hyp...

Cardiovascular diseases are the number one cause of morbidity and mortality worldwide, but the underlying molecular mechanisms remain not well understood. Cardiomyopathies are primary diseases of the heart muscle and contribute to high rates of heart failure and sudden cardiac deaths. Here, we distinguished four different genetic cardiomyopathies b...

OBJECTIVES Clinical experience with continuous flow ventricular assist devices (VADs) in patients with transposition of the great arteries (TGA) including dextro-TGA and congenitally corrected TGA is rare, and indications as well as potential benefits or specific hurdles remain unclear. Therefore, our goal was to report on our experience regarding...

Background: Effects of cranioplasty (CP) and skullcap reimplantation after decompressive craniectomy (DC) for cerebral hemorrhage or malignant brain infarction in patients with left ventricular assist device support (LVAD) as bridge to transplantation has not been surveyed yet. The aim of this study was to evaluate outcome and management after CP...

Background Sleep-disordered breathing (SDB) is a highly common comorbidity in heart failure (HF) patients and appears mainly as obstructive SDB, or central SDB. SDB has been shown to deteriorate quality of life in HF patients, but its presence is also associated with worse prognosis. SDB severity has been shown to mirror HF level and hereby hyperca...

Background In patients with acute myocardial infarction (MI), cardioprotective effects of obstructive sleep apnea are postulated on account of hypoxemic preconditioning. The aim of this single‐center substudy was to investigate a potential association between obstructive sleep apnea and the presence of coronary collaterals in patients with first‐ti...

Sleep apnea and pulmonary hypertension

Assessing hemodynamics, especially central venous pressure (CVP), is essential in heart failure (HF). Right heart catheterization (RHC) is the gold-standard, but non-invasive methods are also needed. However, the role of 2-dimensional echocardiography (2DE) remains uncertain, and 3-dimensional echocardiography (3DE) is not always available. This st...

Aims Mechanical unloading by ventricular assist devices (VADs) has become increasingly important for the therapy of end‐stage heart failure during the last decade. However, VAD support was claimed to be associated with partial reverse remodelling. Unfortunately, the literature describes the contradictory effects of VAD systems on cardiac fibrosis,...

Introduction The remedē System (Respicardia, Inc., Minnetonka, MN), a transvenous phrenic nerve stimulation (TPNS) device that treats central sleep apnea, consists of an implantable pulse generator and a stimulation lead. Stimulation captures the phrenic nerve to contract the diaphragm and expand the lungs similar to normal inspiration. Stimulation...

Purpose Central sleep apnea (CSA) is a highly common comorbidity in heart failure (HF) patients and is known to deteriorate quality of life and prognosis. Effective treatment options are scarce. Transvenous phrenic nerve stimulation (PNS) has been shown to be effective and safe in CSA treatment in HF. However, lead implantation may be difficult or...

Mutations in RBM20 encoding the RNA binding motif protein 20 (RBM20) are associated with an early onset and clinically severe forms of cardiomyopathies. Transcriptome analyses revealed RBM20 as an important regulator of cardiac alternative splicing. RBM20 mutations are especially localized in exons 9 and 11 including the highly conserved arginine a...

The remedē System is a novel fully implantable transvenous phrenic nerve stimulation (TPNS) device developed to treat central sleep apnea. No information is published how to explant or replace its leads. An 81‐year‐old had a fractured lead and we removed it over a wire. However, unbreachable resistances occurred with a new lead deployed over the en...

Introduction Cryoballoon (CB)‐guided ablation of atrial fibrillation (AF) is established in symptomatic AF patients. This study sought to determine the safety and efficacy of CB pulmonary vein isolation (PVI) in young adults. Methods and Results A total of 93 consecutive patients aged <45 years referred to our center for AF ablation were included...

Background Low vitamin D levels have been associated with various diseases, including cardiovascular disease, although data are not consistent. Serum vitamin D levels depend on different synthesis steps which are controlled by gene cascade. This study investigated whether low serum levels of vitamin D and single nucleotide polymorphisms (SNPs) in g...

Introduction Heart transplantation is the desired therapy in end-stage heart failure (HF) and in patients with left-ventricular assist devices (LVAD suffering from life-threatening complications on device. Comorbidities are frequent in end-stage HF and may refrain the patient from being listed for heart transplantation such as infections making sur...

Aims: Centrifugal continuous flow pumps are currently the state of the art in left ventricular assist device therapy. This study was conducted to compare the results after implantation of the HVAD® and the HeartMate 3®. Methods and results: We retrospectively analysed preoperative and post-operative patient data of all 106 patients, who received...

Aims: We aimed to unravel the genetic, molecular and cellular pathomechanisms of DSC2 truncation variants leading to arrhythmogenic cardiomyopathy (ACM). Methods and Results: We report a homozygous 4-bp DSC2 deletion variant c.1913_1916delAGAA, p.Q638LfsX647hom causing a frameshift carried by an ACM patient. Whole exome sequencing and comparative...

Purpose In heart failure with reduced ejection fraction (HFrEF), the effects of automatic positive airway pressure therapy (APAP) for obstructive sleep apnea (OSA) on sleep quality and sympatho-vagal balance (SVB) are unknown. Methods In this randomized controlled trial (6 months of APAP vs. nasal strips as control), sleep quality and SVB in patie...

Aims: In acute myocardial infarction (AMI), impaired myocardial salvage and large infarct size result in residual heart failure, which is one of the most important predictors of morbidity and mortality after AMI. Sleep-disordered breathing (SDB) is associated with reduced myocardial salvage index (MSI) within the first 3 months after AMI. Adaptive...

Patients with a wide variety of cardiovascular diseases, including arterial and pulmonary hypertension, arrhythmia, coronary artery disease and heart failure, are more likely to report impaired sleep with reduced sleep duration and quality, and also, sometimes, sleep interruptions because of paroxysmal nocturnal dyspnoea or arrhythmias. Overall, ob...

Background Despite major advances in knowledge on hypertrophic cardiomyopathy (HCM) at the genetic and molecular levels, the understanding of essential clinical aspects remains limited. The aim of this study is to identify the prevalence and clinical significance of Sleep-disordered Breathing (SDB) in a large patient population. Methods 201 patien...

Introduction and purpose In heart failure with reduced ejection fraction (HFrEF), the effects of automatic positive airway pressure therapy (APAP) for obstructive sleep apnea (OSA) on sleep quality and sympatho-vagal balance (SVB) are unknown. Methods In this randomized controlled trial, sleep quality and SVB in patients with HFrEF and OSA were mo...

Introduction Cardiac arrhythmias are regulary seen in patients following orthotopic heart transplantation (OHT). So far, there is no data available about the prevalence in a large cohort. Methods We retrospectively screened our database for subjects with OHT who received inpatient or outpatient treatment in our center between January 2000 and Dece...

Background Assessing hemodynamics, in particular central venous pressure (CVP) is essential in heart failure diagnostics, leading individual therapy. Hereby, invasive measurement through Swan-Ganz right heart catheterization (RHC) is considered gold standard for patient evaluation, but catheterization implies risks of invasiveness including bleedin...

Introduction Central sleep apnea is highly common in heart failure (HF) patients and often appears as Cheyne-Stokes-respiration (CSR). Presence of CSR in HF has been clearly shown to connote worse prognosis and HF patients with CSR experience increased mortality. Since widely used adaptive servoventilation is now contraindicated in HF with reduced...

Background: Adaptive servoventilation (ASV) effectively treats nocturnal respiratory events in patients with heart failure and reduced ejection fraction (HFrEF) and central sleep apnoea (CSA), but increased mortality has been reported. This study investigated changes in sleep architecture during ASV treatment in HFrEF patients. Methods: A retros...

Study Objective To evaluate long-term efficacy and safety of phrenic nerve stimulation (PNS) in patients with moderate to severe central sleep apnea (CSA) through 3-years of therapy. Methods Patients in the remedē System Pivotal Trial were observed every 3 months after implant until FDA approval. At the time of approval and study closure, all pati...

Pulmonary hypertension(PH) is extremely common in acute decompensated heart failure (ADHF) patients and predicts increased mortality. Obstructive sleep apnea (OSA) is highly prevalent in CHF patients, may contribute to further elevated pulmonary pressures. OBJECTIVES This study evaluates the impact of positive airway pressure (PAP) therapy on PH i...

Aim: To clarify whether unmasking of central sleep apnea during continuous positive airway pressure (CPAP) initiation can be identified from initial diagnostic polysomnography (PSG) in patients with heart failure with reduced ejection fraction (HFREF) and obstructive sleep apnea (OSA) MATERIALS AND METHODS: Forty-three consecutive patients with ob...

Background: Cardiac arrhythmias and sleep-disordered breathing (SDB) are common comorbidities in heart failure with reduced ejection fraction (HFrEF). However, understanding of the association between arrhythmias and SDB is poor. This study assessed the occurrence and circadian distribution of ventricular arrhythmias in HFrEF patients with and wit...

Background: Central sleep apnea (CSA) is highly prevalent in heart failure patients with reduced left ventricular ejection fraction (HF-REF). The Bad Oeynhausen Adaptive Servo-ventilation (ASV) registry (NCT01657188) was designed to investigate whether treatment of CSA with ASV improved survival in HF-REF patients; the effects of ASV on symptoms a...

Purpose of Review Sleep-disordered breathing (SDB) is an independent risk factor for cardiovascular disease. SDB-related changes in the autonomic nervous system (ANS) and the association between obstructive sleep apnea and atrial fibrillation (Afib) have been extensively researched. SDB has also been associated with occurrence of ventricular arrhyt...