Omitting transesophageal echocardiography before catheter ablation of atrial fibrillation.

BACKGROUND: Data about necessity of performing transesophageal echocardiography (TOE) prior to every catheter ablation (CA) of atrial fibrillation (AF) is scarce. We aimed to evaluate the safety of an individualized risk-based approach to TOE with respect to thromboembolic cerebrovascular events (CVE) in patients undergoing CA for AF or left atrial tachycardia (AT). METHODS: We performed a retrospective clinical study based on our institutional registry database. Patients undergoing CA for AF or left-sided AT following initial AF ablation at two participating centers were enrolled. Prior to the procedure, patients were scheduled for TOE only if they had a history of thromboembolic stroke, left atrial appendage (LAA) thrombus, or inappropriate anticoagulation regimen in the previous 3 to 4 weeks. The incidence of periprocedural cerebrovascular thromboembolic events was assessed. RESULTS: We analyzed 1155 patients (median age 70 years, 54.8% male, 48.1% had persistent AF/AT). In 261 patients, a TOE was performed; in 2 patients (0.7%), an LAA thrombus was detected, which led to cancellation of the catheter ablation; in 894 patients, the TOE was omitted. Of the 1153 (0.35%) patients who underwent ablation, 4 (0.35%) experienced a CVE (one TIA and three strokes). The rate of CVE in our study does not exceed that reported in most multicenter trials. The low event rates limited statistical analysis of possible risk factors for CVE. In all 4 patients with CVE, post-CVE imaging showed the absence of LAA thrombus. CONCLUSIONS: An individualized selective approach to TOE before catheter ablation of AF or left AT showed a very low risk of overt intraprocedural thromboembolic events for the population in our study. A further randomized controlled study is needed to determine whether TOE prior to catheter ablation without ICE could be omitted in patients with uninterrupted OAC without previous thromboembolic events or a history of left atrial thrombus.

Mst4, a novel cardiac STRIPAK complex-associated kinase, regulates cardiomyocyte growth and survival and is upregulated in human cardiomyopathy.

Myocardial failure is associated with adverse remodeling, including loss of cardiomyocytes, hypertrophy, and alterations in cell-cell contacts. Striatin-interacting phosphatase and kinase (STRIPAK) complexes and their mammalian STE20-like kinase 4 (Mst4) have been linked to development of different diseases. The role and targets of Mst4 in cardiomyocytes have not been investigated yet. Multitissue immunoblot experiments show highly enriched Mst4 expression in rodent hearts. Analyses of human biopsy samples from patients suffering from dilated cardiomyopathy revealed that Mst4 is upregulated (5- to 8-fold p < 0.001) compared with nonfailing controls. Increased abundance of Mst4 could also be detected in mouse models of cardiomyopathy. We confirmed that Mst4 interacts with STRIPAK components in neonatal rat ventricular cardiomyocytes, indicating that STRIPAK is present in the heart. Immunofluorescence stainings and molecular interaction studies revealed that Mst4 is localized to the intercalated disc and interacts with several intercalated disc proteins. Overexpression of Mst4 in cardiomyocytes results in hypertrophy compared with controls. In adult rat cardiomyocytes, Mst4 overexpression increases cellular and sarcomeric fractional shortening (p < 0.05), indicating enhanced contractility. Overexpression of Mst4 also inhibits apoptosis shown by reduction of cleaved caspase3 (-69%, p < 0.0001), caspase7 (-80%, p < 0.0001), and cleaved Parp1 (-27%, p < 0.001). To elucidate potential Mst4 targets, we performed phosphoproteomics analyses in neonatal rat cardiomyocytes after Mst4 overexpression and inhibition. The results revealed target candidates of Mst4 at the intercalated disc. We identified Mst4 as a novel cardiac kinase that is upregulated in cardiomyopathy-regulating cardiomyocyte growth and survival.

Transcatheter or Surgical Treatment of Aortic-Valve Stenosis.

BACKGROUND: Among low-risk patients with severe, symptomatic aortic stenosis who are eligible for both transcatheter aortic-valve implantation (TAVI) and surgical aortic-valve replacement (SAVR), data are lacking on the appropriate treatment strategy in routine clinical practice. METHODS: In this randomized noninferiority trial conducted at 38 sites in Germany, we assigned patients with severe aortic stenosis who were at low or intermediate surgical risk to undergo either TAVI or SAVR. Percutaneous- and surgical-valve prostheses were selected according to operator discretion. The primary outcome was a composite of death from any cause or fatal or nonfatal stroke at 1 year. RESULTS: A total of 1414 patients underwent randomization (701 to the TAVI group and 713 to the SAVR group). The mean (±SD) age of the patients was 74±4 years; 57% were men, and the median Society of Thoracic Surgeons risk score was 1.8% (low surgical risk). The Kaplan-Meier estimate of the primary outcome at 1 year was 5.4% in the TAVI group and 10.0% in the SAVR group (hazard ratio for death or stroke, 0.53; 95% confidence interval [CI], 0.35 to 0.79; P<0.001 for noninferiority). The incidence of death from any cause was 2.6% in the TAVI group and 6.2% in the SAVR group (hazard ratio, 0.43; 95% CI, 0.24 to 0.73); the incidence of stroke was 2.9% and 4.7%, respectively (hazard ratio, 0.61; 95% CI, 0.35 to 1.06). Procedural complications occurred in 1.5% and 1.0% of patients in the TAVI and SAVR groups, respectively. CONCLUSIONS: Among patients with severe aortic stenosis at low or intermediate surgical risk, TAVI was noninferior to SAVR with respect to death from any cause or stroke at 1 year. (Funded by the German Center for Cardiovascular Research and the German Heart Foundation; DEDICATE-DZHK6 ClinicalTrials.gov number, NCT03112980.).

Tricuspid Regurgitation and TAVR: Outcomes, Risk Factors and Biomarkers.

Background. The significance of concomitant tricuspid regurgitation (TR) in the context of transcatheter aortic valve replacement (TAVR) remains unclear. This study aimed to analyze the severity of TR before and after TAVR with regard to short- and long-term survival and to analyze the influencing factors. Methods. In our retrospective analysis, TR before and after TAVR was examined and patients were classified into groups accordingly. Special attention was paid to patients with post-interventional changes in TR. Mortality after TAVR was considered the primary endpoint of the analysis and major complications according to the Valve Academic Research Consortium 3 (VARC3) were compared. Moreover, biomarkers and risk factors for worsening or improvement of TR through TAVR were analyzed. Results. Among 775 patients who underwent TAVR in our center between January 2009 and December 2019, 686 patients (89%) featured low- and 89 patients (11%) high-grade TR. High-grade pre-TAVR TR was associated with worse short- (30-day), mid- (2-year) and long-term survival up to 8 years. Even though in nearly half of the patients with high-grade TR the regurgitation improved within seven days after TAVR (n = 42/89), this did not result in a survival benefit for this subgroup. On the other hand, a worsening of low-grade TR was seen in more than 10% of the patients (n = 73/686), which was also associated with a worse prognosis. Predictors of worsening of TR after TAVR were adipositas, impaired right ventricular function and the presence of mild TR. Age, atrial fibrillation, COPD, impaired renal function and elevated cardiac biomarkers were risk factors for mortality after TAVR independent from the grade of TR. Conclusions. Not only pre-interventional, but also post-TAVR high-grade TR is associated with a worse prognosis after TAVR. TAVR can change concomitant tricuspid regurgitation, but improvement does not have any impact on short- and long-term survival. Worsening of TR after TAVR is possible and impairs the prognosis.

A streamlined pathway for transcatheter aortic valve implantation: the BENCHMARK study.

BACKGROUND AND AIMS: There is significant potential to streamline the clinical pathway for patients undergoing transcatheter aortic valve implantation (TAVI). The purpose of this study was to evaluate the effect of implementing BENCHMARK best practices on the efficiency and safety of TAVI in 28 sites in 7 European countries. METHODS: This was a study of patients with severe symptomatic aortic stenosis (AS) undergoing TAVI with balloon-expandable valves before and after implementation of BENCHMARK best practices. Principal objectives were to reduce hospital length of stay (LoS) and duration of intensive care stay. Secondary objective was to document patient safety. RESULTS: Between January 2020 and March 2023, 897 patients were documented prior to and 1491 patients after the implementation of BENCHMARK practices. Patient characteristics were consistent with a known older TAVI population and only minor differences. Mean LoS was reduced from 7.7 ± 7.0 to 5.8 ± 5.6 days (median 6 vs. 4 days; P < .001). Duration of intensive care was reduced from 1.8 to 1.3 days (median 1.1 vs. 0.9 days; P < .001). Adoption of peri-procedure best practices led to increased use of local anaesthesia (96.1% vs. 84.3%; P < .001) and decreased procedure (median 47 vs. 60 min; P < .001) and intervention times (85 vs. 95 min; P < .001). Thirty-day patient safety did not appear to be compromised with no differences in all-cause mortality (0.6% in both groups combined), stroke/transient ischaemic attack (1.4%), life-threatening bleeding (1.3%), stage 2/3 acute kidney injury (0.7%), and valve-related readmission (1.2%). CONCLUSIONS: Broad implementation of BENCHMARK practices contributes to improving efficiency of TAVI pathway reducing LoS and costs without compromising patient safety.

Trans-Brachial TAVI in a Patient with Aortic Isthmus Stenosis: A Case Report.

BACKGROUND: TAVI indications expand not only to low-risk patients but also to patients with a more complex anatomy and comorbidities. Transfemoral retrograde access is recognized as the first preferred approach according to the current guidelines. However, this approach is not suitable in up to 10-15% of patients, for whom an alternative non-femoral access route is required. CASE PRESENTATION: An 83-year-old male patient with known aortic isthmus stenosis presented with severe symptomatic aortic stenosis. Computed tomography revealed a subtotal isthmus stenosis, directly after left subclavian artery origin, with many collaterals extending toward the axillary and subclavian arteries. Duplex ultrasound verified the proximal diameter of the left brachial artery to be 5.5 mm. A successful surgical cutdown trans-brachial TAVI with an Evolut prosthetic valve with a size of 29 mm was performed. On the fourth postoperative day, the patient was discharged, and the three-month follow-up was uneventful. CONCLUSION: In patients with aortic isthmus stenosis, the brachial artery could be a feasible alternative, as a less invasive access site, which can be determined after careful assessment of the vessel diameter. More data are required to evaluate the safety and efficacy of this access route and to achieve more technical improvements to increase operator familiarity with it.

Regnase-1 overexpression as a therapeutic approach of Marfan syndrome.

Rupture or dissection of thoracic aortic aneurysms is still the leading cause of death for patients diagnosed with Marfan syndrome. Inflammation and matrix digestion regulated by matrix metalloproteases (MMPs) play a major role in the pathological remodeling of the aortic media. Regnase-1 is an endoribonuclease shown to cleave the mRNA of proinflammatory cytokines, such as interleukin-6. Considering the major anti-inflammatory effects of regnase-1, here, we aimed to determine whether adeno-associated virus (AAV)-mediated vascular overexpression of the protein could provide protection from the development and progression of aortic aneurysms in Marfan syndrome. The overexpression of regnase-1 resulted in a marked decrease in inflammatory parameters and elastin degradation in aortic smooth muscle cells in vitro. Intravenous injection of a vascular-targeted AAV vector resulted in the efficient transduction of the aortic wall and overexpression of regnase-1 in a murine model of Marfan syndrome, associated with lower circulating levels of proinflammatory cytokines and decreased MMP expression and activity. Regnase-1 overexpression strongly improved elastin architecture in the media and reduced aortic diameter at distinct locations. Therefore, AAV-mediated regnase-1 overexpression may represent a novel gene therapy approach for inhibiting aortic aneurysms in Marfan syndrome.

Complications in patients with cardiogenic shock on veno-arterial extracorporeal membrane oxygenation therapy: distribution and relevance. Results from an international, multicentre cohort study.

AIMS: Veno-arterial extracorporeal membrane oxygenation therapy (VA-ECMO) restores circulation and tissue oxygenation in cardiogenic shock (CS) patients, but can also lead to complications. This study aimed to quantify VA-ECMO complications and analyse their association with overall survival as well as favourable neurological outcome (cerebral performance categories 1 + 2). METHODS AND RESULTS: All-comer patients with CS treated with VA-ECMO were retrospectively enrolled from 16 centres in four countries (2005-2019). Neurological, bleeding, and ischaemic adverse events (AEs) were considered. From these, typical VA-ECMO complications were identified and analysed separately as device-related complications. n = 501. Overall, 118 were women (24%), median age was 56.0 years, median lactate was 8.1 mmol/L. Acute myocardial infarction caused CS in 289 patients (58%). Thirty-days mortality was 40% (198/501 patients). At least one device-related complication occurred in 252/486 (52%) patients, neurological AEs in 108/469 (23%), bleeding in 192/480 (40%), ischaemic AEs in 123/478 (26%). The 22% of patients with the most AEs accounted for 50% of all AEs. All types of AEs were associated with a worse prognosis. Aside from neurological ones, all AEs and device-related complications were more likely to occur in women; although prediction of AEs outside of neurological AEs was generally poor. CONCLUSION: Therapy and device-related complications occur in half of all patients treated with VA-ECMO and are associated with a worse prognosis. They accumulate in some patients, especially in women. Aside from neurological events, identification of patients at risk is difficult, highlighting the need to establish additional quantitative markers of complication risk to guide VA-ECMO treatment in CS.

Producing and Testing Prototype Tissue-Engineered 3D Tri-Leaflet Valved Stents on Biodegradable Poly-ε-Caprolactone Scaffolds.

Transcatheter pulmonary valve replacement is a minimally-invasive alternative treatment for right ventricular outflow tract dysfunction and has been rapidly evolving over the past years. Heart valve prostheses currently available still have major limitations. Therefore, one of the significant challenges for the future is the roll out of transcatheter tissue engineered pulmonary valve replacement to more patients. In the present study, biodegradable poly-ε-caprolactone (PCL) nanofiber scaffolds in the form of a 3D leaflet matrix were successfully seeded with human endothelial colony-forming cells (ECFCs), human induced pluripotent stem cell-derived MSCs (hMSCs), and porcine MSCs (pMSCs) for three weeks for the generation of 3D tissue-engineered tri-leaflet valved stent grafts. The cell adhesion, proliferation, and distribution of these 3D heart leaflets was analyzed using fluorescence microscopy and scanning electron microscopy (SEM). All cell lineages were able to increase the overgrown leaflet area within the three-week timeframe. While hMSCs showed a consistent growth rate over the course of three weeks, ECFSs showed almost no increase between days 7 and 14 until a growth spurt appeared between days 14 and 21. More than 90% of heart valve leaflets were covered with cells after the full three-week culturing cycle in nearly all leaflet areas, regardless of which cell type was used. This study shows that seeded biodegradable PCL nanofiber scaffolds incorporated in nitinol or biodegradable stents will offer a new therapeutic option in the future.

Transcriptional Targeting Approaches in Cardiac Gene Transfer Using AAV Vectors.

Cardiac-targeted transgene delivery offers new treatment opportunities for cardiovascular diseases, which massively contribute to global mortality. Restricted gene transfer to cardiac tissue might protect extracardiac organs from potential side-effects. This could be mediated by using cis-regulatory elements, including promoters and enhancers that act on the transcriptional level. Here, we discuss examples of tissue-specific promoters for targeted transcription in myocytes, cardiomyocytes, and chamber-specific cardiomyocytes. Some promotors are induced at pathological states, suggesting a potential use as "induction-by-disease switches" in gene therapy. Recent developments have resulted in the identification of novel enhancer-elements that could further pave the way for future refinement of transcriptional targeting, for example, into the cardiac conduction system.

Amino acid auxotrophies in human gut bacteria are linked to higher microbiome diversity and long-term stability.

Amino acid auxotrophies are prevalent among bacteria. They can govern ecological dynamics in microbial communities and indicate metabolic cross-feeding interactions among coexisting genotypes. Despite the ecological importance of auxotrophies, their distribution and impact on the diversity and function of the human gut microbiome remain poorly understood. This study performed the first systematic analysis of the distribution of amino acid auxotrophies in the human gut microbiome using a combined metabolomic, metagenomic, and metabolic modeling approach. Results showed that amino acid auxotrophies are ubiquitous in the colon microbiome, with tryptophan auxotrophy being the most common. Auxotrophy frequencies were higher for those amino acids that are also essential to the human host. Moreover, a higher overall abundance of auxotrophies was associated with greater microbiome diversity and stability, and the distribution of auxotrophs was found to be related to the human host's metabolome, including trimethylamine oxide, small aromatic acids, and secondary bile acids. Thus, our results suggest that amino acid auxotrophies are important factors contributing to microbiome ecology and host-microbiome metabolic interactions.

Transcatheter Aortic Valve Implantation by Intercostal Access: Initial Experience with a No-Touch Technique.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is now a well-established therapeutic option in an elderly high-risk patient cohort with aortic valve disease. Although most commonly performed via a transfemoral route, alternative approaches for TAVI are constantly being improved. Instead of the classical mini-sternotomy, it is possible to achieve a transaortic access via a right anterior mini-thoracotomy in the second intercostal space. We describe our experience with this sternum- and rib-sparing technique in comparison to the classical transaortic approach. METHODS: Our retrospective study includes 173 patients who were treated in our institution between January 2017 and April 2020 with transaortic TAVI via either upper mini-sternotomy or intercostal thoracotomy. The primary endpoint was 30-day mortality, and secondary endpoints were defined as major postoperative complications that included admission to the intensive care unit and overall hospital stay, according to the Valve Academic Research Consortium 3. RESULTS: Eighty-two patients were treated with TAo-TAVI by upper mini-sternotomy, while 91 patients received the intercostal approach. Both groups were comparable in age (mean age: 82 years) and in the proportion of female patients. The intercostal group had a higher rate of peripheral artery disease (41% vs. 22%, p = 0.008) and coronary artery disease (71% vs. 40%, p < 0.001) with a history of percutaneous coronary intervention or coronary artery bypass grafting, resulting in significantly higher preinterventional risk evaluation (EuroScore II 8% in the intercostal vs. 4% in the TAo group, p = 0.005). Successful device implantation and a reduction of the transvalvular gradient were achieved in all cases with a significantly lower rate of trace to mild paravalvular leakage in the intercostal group (12% vs. 33%, p < 0.001). The intercostal group required significantly fewer blood transfusions (0 vs. 2 units, p = 0.001) and tended to require less reoperation (7% vs. 15%, p = 0.084). Hospital stays (9 vs. 12 d, p = 0.011) were also shorter in the intercostal group. Short- and long-term survival in the follow-up showed comparable results between the two approaches (30-day, 6-month- and 2-year mortality: 7%, 23% and 36% in the intercostal vs. 9%, 26% and 33% in the TAo group) with acute kidney injury (AKI) and reintubation being independent risk factors for mortality. CONCLUSIONS: Transaortic TAVI via an intercostal access offers a safe and effective treatment of aortic valve stenosis.

Quality of Life Measures in Aortic Stenosis Research: A Narrative Review.

BACKGROUND: Elderly patients with aortic stenosis (AS) not only have a reduced life expectancy but also a reduced quality of life (QoL). The benefits of an AS intervention may be considered a balance between a good QoL and a reasonably extended life. However, the different questionnaires being used to determine the QoL were generally not developed for the specific situation of patients with AS and come with strengths and considerable weaknesses. The objective of this article was to provide an overview of the available QoL instruments in AS research, describe their strengths and weaknesses, and provide our assessment of the utility of the available scoring instruments for QoL measurements in AS. SUMMARY: We identified and reviewed the following instruments that are used in AS research: Short Form Health Survey (SF-36/SF-12), EuroQol-5D (EQ-5D), the Illness Intrusiveness Rating Scale (IIRS), the HeartQoL, the Kansas City Cardiomyopathy Questionnaire (KCCQ), the Minnesota Living with Heart Failure Questionnaire (MLHF), the MacNew Questionnaire, and the Toronto Aortic Stenosis Quality of Life Questionnaire (TASQ). KEY MESSAGES: There is no standardized assessment of QoL in patients with AS. Many different questionnaires are being used, but they are rarely specific for AS. There is a need for AS-specific research into the QoL of patients as life prolongation may compete for an improved QoL in this elderly patient group.

Low extracellular vesicle concentrations predict survival in patients with heart failure.

Background: Heart disease is of worldwide importance due to high morbidity and mortality. Extracellular vesicle (EV) concentration and size represent novel diagnostic and prognostic biomarkers, e.g. in patients with liver cancer, but data on their prognostic relevance in heart disease are lacking. Here, we investigated the role of EV concentration, size and zeta potential in patients with heart disease. Methods: Vesicle size distribution, concentration and zeta potential were measured by nanoparticle tracking analysis (NTA) in 28 intensive care unit (ICU) and 20 standard care (SC) patients and 20 healthy controls. Results: Patients with any disease had a lower zeta potential compared to the healthy controls. Vesicle size (X50) was significantly higher in ICU patients (245 nm) with heart disease as compared to those patients with heart disease receiving standard care (195 nm), or healthy controls (215 nm) (p = 0.001). Notably, EV concentration was lower in ICU patients with heart disease (4.68 × 1010 particles/ml) compared to SC patients with heart disease (7,62 × 1010 particles/ml) and healthy controls (1.50 × 1011 particles/ml) (p = 0.002). Extracellular vesicle concentration is prognostic for overall survival in patients with heart disease. Overall survival is significantly reduced when the vesicle concentration is below 5.55 × 1010 particles/ml. Median overall survival was only 140 days in patients with vesicle concentrations below 5.55 × 1010 particles/ml compared to 211 days in patients with vesicle concentrations above 5.55 × 1010 particles/ml (p = 0.032). Summary: Concentration of EVs is a novel prognostic marker in ICU and SC patients with heart disease.

Is the outcome of elective vs non-elective patients undergoing transcatheter aortic valve implantation different? Results of a single-centre, observational assessment of outcomes at a large university clinic.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) can either be conducted as an elective (scheduled in advance) or a non-elective procedure performed during an unplanned hospital admission. The objective of this study was to compare the outcomes of elective and non-elective TAVI patients. METHODS: This single-centre study included 512 patients undergoing transfemoral TAVI between October 2018 and December 2020; 378 (73.8%) were admitted for elective TAVI, 134 (26.2%) underwent a non-elective procedure. Our TAVI programme entails an optimized fast-track concept aimed at minimizing the total length of stay to ≤ 5 days for elective patients which in the German healthcare system is currently defined as the minimal time period to safely perform TAVI. Clinical characteristics and survival rates at 30 days and 1 year were analysed. RESULTS: Patients who underwent non-elective TAVI had a significantly higher comorbidity burden. Median duration from admission to discharge was 6 days (elective group 6 days versus non-elective group 15 days; p < 0.001), including a median postprocedural stay of 5 days (elective 4 days versus non-elective 7 days; p < 0.001). All-cause mortality at 30 days was 1.1% for the elective group and 3.7% for non-elective patients (p = 0.030). At 1 year, all-cause mortality among elective TAVI patients was disproportionately lower than in non-elective patients (5.0% versus 18.7%, p < 0.001). In the elective group, 54.5% of patients could not be discharged early due to comorbidities or procedural complications. Factors associated with a failure of achieving a total length of stay of ≤ 5 days comprised frailty syndrome, renal impairment as well as new permanent pacemaker implantation, new bundle branch block or atrial fibrillation, life-threatening bleeding, and the use of self-expanding valves. After multivariate adjustment, new permanent pacemaker implantation (odds ratio 6.44; 95% CI 2.59-16.00), life-threatening bleeding (odds ratio 4.19; 95% confidence interval 1.82-9.66) and frailty syndrome (odds ratio 5.15; 95% confidence interval 2.40-11.09; all p < 0.001, respectively) were confirmed as significant factors. CONCLUSIONS: While non-elective patients had acceptable periprocedural outcomes, mortality rates at 1 year were significantly higher compared to elective patients. Approximately only half of elective patients could be discharged early. Improvements in periprocedural care, follow-up strategies and optimized treatment of both elective and non-elective TAVI patients are needed.

Fibin regulates cardiomyocyte hypertrophy and causes protein-aggregate-associated cardiomyopathy in vivo.

Despite the identification of numerous molecular pathways modulating cardiac hypertrophy its pathogenesis is not completely understood. In this study we define an unexpected role for Fibin ("fin bud initiation factor homolog") in cardiomyocyte hypertrophy. Via gene expression profiling in hypertrophic murine hearts after transverse aortic constriction we found a significant induction of Fibin. Moreover, Fibin was upregulated in another mouse model of cardiac hypertrophy (calcineurin-transgenics) as well as in patients with dilated cardiomyopathy. Immunoflourescence microscopy revealed subcellular localization of Fibin at the sarcomeric z-disc. Overexpression of Fibin in neonatal rat ventricular cardiomyocytes revealed a strong anti-hypertrophic effect through inhibiting both, NFAT- and SRF-dependent signalling. In contrast, transgenic mice with cardiac-restricted overexpression of Fibin developed dilated cardiomyopathy, accompanied by induction of hypertrophy-associated genes. Moreover, Fibin overexpression accelerated the progression to heart failure in the presence of prohypertrophic stimuli such as pressure overload and calcineurin overexpression. Histological and ultrastructural analyses surprisingly showed large protein aggregates containing Fibin. On the molecular level, aggregate formation was accompanied by an induction of the unfolded protein response subsequent UPR-mediated apoptosis and autophagy. Taken together, we identified Fibin as a novel potent negative regulator of cardiomyocyte hypertrophy in vitro. Yet, heart-specific Fibin overexpression in vivo causes development of a protein-aggregate-associated cardiomyopathy. Because of close similarities to myofibrillar myopathies, Fibin represents a candidate gene for cardiomyopathy and Fibin transgenic mice may provide additional mechanistic insight into aggregate formation in these diseases.