Search Results (1,134)

Background/Objectives: Excessive trabeculation of the left ventricle, previously known as left ventricular non-compaction (LVNC), is a rare phenotypic trait whose mechanisms and pathogenesis still remain conflictual. Its presentations may range from heart failure to embolism and, most importantly, ventricular arrhythmias (VAs). This study aims to find novel predictive factors for the occurrence of potentially fatal VAs in patients with left ventricular hypertrabeculation. Methods: All consecutive patients meeting the echocardiographic (Chin, Jenny or Stöllberger) and/or MRI criteria (Petersen) for hypertrabeculation were prospectively enrolled from October 2009 to December 2023. The primary outcome was a composite of sudden cardiac death, sustained ventricular tachycardias (sVTs), ventricular fibrillation (VF) or appropriate implantable cardioverter defibrillator (ICD) interventions. The secondary outcome was a composite of cardiovascular death and cardiovascular hospitalizations. Results: Overall, 64 patients (41 males, mean age 46 ± 19 years old) were enrolled and followed for a median time of 2.2 years. Six patients (9.4%) experienced a composite outcome at eight years, three with previous sVTs and three with previous non-sustained VTs (nsVTs). The strongest predictor of the primary endpoint was the anamnesis of nsVTs and sVTs before LVNC diagnosis. In addition, nsVTs and sVTs were significantly associated with the secondary outcome. Conclusions: Hypertrabeculation of the left ventricle is a complex and poorly understood condition whose status of cardiomyopathy is currently challenged. In our population, patients with a trabecular pattern experienced a high incidence of VAs, cardiovascular death and hospitalizations. VAs before LVNC diagnosis were predictive of the outcome independently from systolic function. Full article

Background: Emerging evidence highlights the importance of the MIF–sCD74 axis in health and disease, including its role in regulating cell death. While studies in routine cardiac surgery suggest perioperative relevance, its role in end-stage heart failure (ESFH) patients undergoing left ventricular assist device (LVAD) implantation remains unexplored. Moreover, although MIF and sCD74 induce necroptosis in neonatal cardiac myofibroblasts, the effects of MIF, its paralog D-DT, and sCD74 on adult cardiac myofibroblasts (CMFs) are unknown. Methods: Plasma concentrations of sCD74, MIF and D-DT were measured perioperatively in a small cohort of patients with ESHF undergoing LVAD implantation (n = 20). As a preclinical model of ESHF, primary adult CMFs were treated with recombinant MIF, D-DT and sCD74 to evaluate their effects on cellular viability and health. Results: In LVAD patients, sCD74 and D-DT levels were significantly increased 24 h postoperatively, whereas MIF levels were reduced compared to baseline. ROC curve analysis demonstrated a good discriminatory power of 24 h post-OP sCD74 (AUC = 0.83), sCD74/MIF ratio (AUC = 0.82), and D-DT levels (AUC = 0.88) for acute kidney injury, composite outcome, and right heart failure (RHF), respectively. In adult CMFs, MIF and sCD74 synergistically reduced viable cell counts (p = 0.0083), whereas D-DT reduced cell counts in an sCD74-independent manner (p = 0.0004). Yet, measures of metabolism, proliferation, apoptosis and necrosis along with inflammatory gene expression remained unchanged. Conclusions: Our findings indicate that the balance of MIF, D-DT, and sCD74 during LVAD implantation may be clinically relevant. In particular, an imbalance characterized by elevated sCD74 or D-DT and reduced MIF levels 24 h post-surgery was associated with unfavorable clinical outcomes. Yet, the current findings are exploratory and hypothesis-generating because of a small sample size. Thus, the prognostic value of plasma levels for postoperative complications after LVAD implantation, and the effects of MIF/D-DT/sCD74 imbalance on cardiac myofibroblasts, need to be validated in larger cohorts and in advanced human experimental models. Full article

Background and objectives: Valve-in-valve transcatheter aortic valve replacement (ViV TAVR) has become an established treatment for failed surgical bioprostheses in patients at high surgical risk. However, procedures performed in degenerated stentless aortic valves remain particularly challenging because of the absence of a radiopaque frame, variable surgical implantation techniques, and a potentially increased risk of coronary obstruction. Evidence in this specific setting is limited. We conducted a systematic review of the literature to identify studies reporting ViV TAVI in degenerated stentless surgical bioprostheses. Materials and methods: Case reports and case series were included when patient-level or clearly identifiable data were available. Baseline characteristics, anatomical features, procedural strategies, and clinical outcomes were extracted and analyzed using a descriptive approach. A total of 54 studies were included, encompassing 294 ViV TAVI procedures performed in failed stentless aortic valves. Results: The mean patient age was 73.9 years, and the average STS-PROM score was 13.45%, reflecting a high-risk population. The most frequently treated prosthesis was the Medtronic Freestyle valve, and the predominant mechanism of failure was regurgitation. Transfemoral access represented the most common approach, while balloon-expandable and self-expanding transcatheter valves were used with similar frequency. Coronary protection strategies were adopted in a minority of procedures, whereas adjunctive procedural techniques such as pre- or post-dilation were relatively common. Device-related complications were mainly driven by coronary obstruction, while cardiac complications included myocardial infarction and unplanned coronary intervention. Overall, VARC-3 device success was achieved in the majority of procedures, with acceptable short-term mortality despite the complexity of the treated population. Conclusions: ViV TAVR in degenerated stentless bioprostheses appears feasible and generally effective but remains associated with specific procedural challenges, particularly related to coronary obstruction risk. Careful anatomical assessment and tailored procedural planning are essential, and larger contemporary studies are needed to better define optimal management strategies in this complex setting. Full article

Emery–Dreifuss muscular dystrophy (EDMD) is a rare inherited neuromuscular disorder within the spectrum of nuclear envelope diseases, classically characterized by early musculo-tendinous contractures, slowly progressive myopathy, and cardiac involvement dominated by conduction disease and arrhythmias, with variable evolution toward cardiomyopathy and heart failure. This narrative review provides a comprehensive and clinically actionable synthesis of cardiovascular manifestations across EDMD genotypes and phenotypes, outlining pragmatic diagnostic and therapeutic pathways for real-world care. A targeted literature search was performed in PubMed, Embase, and Web of Science, focusing on studies addressing cardiovascular involvement in EDMD. Relevant original studies, case series, registries, guideline documents, and high-quality reviews were selected and synthesized narratively, with particular emphasis on diagnostic strategies, risk stratification, and management approaches. Cardiac involvement in EDMD encompasses a broad and heterogeneous spectrum, including atrial disease and conduction disturbances, ventricular arrhythmias, dilated cardiomyopathy, thromboembolic complications, and sudden cardiac death. Phenotypic expression varies according to the underlying genetic substrate, with distinct atrial- and ventricular-dominant trajectories. Early recognition and structured cardiovascular surveillance are essential to guide timely intervention, including anticoagulation, device therapy, and heart failure management. Despite growing awareness, significant gaps remain in risk prediction and standardized management strategies. EDMD represents a paradigmatic model of cardiomyopathy characterized by prominent electrical instability and systemic involvement. A structured, genotype- and phenotype-informed approach centered on early surveillance, proactive arrhythmia and thromboembolic risk management and timely device therapy may improve clinical decision-making in real-world settings. Future perspectives include the integration of precision medicine and the development of gene- and pathway-targeted therapies, with the potential to shift from symptomatic management toward disease-modifying strategies. Full article

Background/Objectives: Palpitations are among the most common reasons for cardiology referrals. Despite widespread use of ambulatory cardiac monitoring, contemporary data from the Middle East are scarce. Extended Holter monitoring provides detailed evaluation of arrhythmia burden, autonomic regulation, and symptom–rhythm correlation in routine clinical practice. Methods: We conducted a prospective observational study of consecutive patients presenting with palpitations who underwent 24–96 h ambulatory Holter monitoring at a cardiology outpatient clinic in Saudi Arabia in 2025. Demographic and clinical characteristics, comorbidities, medication use, echocardiographic parameters, heart rate variability (HRV), ventricular and supraventricular ectopy, tachyarrhythmias, and symptom diary activations were systematically evaluated. Results: Among 251 patients (mean age 41.9 ± 16.4 years; 35.5% male), Holter monitoring showed excellent recording quality (mean analyzable time 98.7 ± 9.5%). Premature ventricular contractions (PVCs) were detected in 53.4% of patients, but burden was low (median 0.0%, IQR 0–0.1%), with only 4.4% exceeding 10%. Atrial premature contractions (APCs) were common (92.0%), though usually low-burden (median burden 0.0%, IQR 0–0.1%); atrial fibrillation and supraventricular tachycardia were rare (0.8% each). Symptom diary activation occurred in 116 patients (46.2%), with 996 events; most (87.9%) correlated with sinus tachycardia, while only 8.6% correlated with PVCs and 2.6% with APCs. In the remaining 53.8% of patients, no symptom–rhythm correlation was documented during monitoring. Heart rate variability showed expected age-related changes. Conclusions: In this predominantly young cohort, Holter monitoring revealed frequent low-burden atrial and ventricular ectopy, whereas clinically significant tachyarrhythmias were uncommon. Holter monitoring up to 96 h provided a diagnostic yield in approximately 50% of patients and should be considered a first-line screening tool. Patients without diagnostic findings may require prolonged monitoring using external or implantable devices. Full article

Background/Objectives: Heart failure (HF) is associated with substantial morbidity, impaired quality of life (QOL), and reduced functional capacity. In selected patients with symptomatic HF despite Optimal Medical Therapy (OMT), Cardiac Contractility Modulation (CCM) may be a therapeutic option. Identifying patients most likely to benefit from CCM remains an unmet need. The Predict-CCM study aims to evaluate long-term clinical and objective outcomes after CCM therapy and to assess the predictive value of pre-implant low-dose dobutamine stress echocardiography (LDDSE). Methods and Results: Predict-CCM is an independent, non-profit, multicenter, observational cohort study conducted in Italy, with both retrospective and prospective enrollment. The primary endpoint is the proportion of subjects with a clinical response to CCM at 12 months, defined as a ≥1-class reduction in NYHA class. Secondary clinical endpoints include reductions in HF-related hospitalizations, changes in QOL assessed by the Minnesota Living with Heart Failure Questionnaire (MLHFQ), and changes in NT-proBNP levels from baseline to follow-up. Outcomes will be evaluated in the overall cohort and in two subcohorts stratified by pre-implant LDDSE response: (1) reduction in left ventricular end systolic volume (LVESV) ≥ 15% (DeltaLVESV ≥ 15%); and (2) reduction in LVESV < 15% (DeltaLVESV < 15%). Assuming a 70% clinical response rate at 12 months, the estimated sample size is 120 patients. The study was approved by the Ethics Committee in March 2025. Enrollment will continue for 2 years, with a 12-month follow-up period after implant for each subject. Conclusions: This study may provide new criteria for patient selection and outcome assessment in CCM therapy. Left ventricular contractile reserve assessed by stress echocardiography may be a promising predictor of response. Full article

Four-dimensional (4D) printing integrates additive manufacturing with stimuli-responsive materials to fabricate biomedical implants and functional healthcare devices that undergo programmed, time-dependent changes in shape or function. Unlike static 3D-printed constructs, 4D-printed systems can respond to clinically relevant stimuli such as temperature, hydration, pH, light (including near-infrared), magnetic fields, or electrical inputs. These triggers drive defined actuation mechanisms, most commonly thermomechanical shape-memory recovery, swelling-induced morphing, and magnetothermal activation. This review synthesizes the principal material platforms used for biomedical 4D printing, including shape-memory polymers and alloys, hydrogels, liquid-crystal elastomers, and responsive composites, and links material choice to device behavior and translational feasibility. Applications are discussed across self-expanding stents, cardiac occluders, tissue-engineered constructs, implantable drug delivery systems, and adaptive wearables. Key translational challenges include sterilization compatibility, manufacturing reproducibility and quality control, safe stimulus delivery, predictable biodegradation and long-term biocompatibility, and regulatory pathway definition. Full article

Percutaneous left atrial appendage occlusion (LAAO) has become an established alternative to long-term oral anticoagulation for stroke prevention in patients with atrial fibrillation, with expanding indications beyond those with absolute contraindications to anticoagulation. Alongside its broader adoption, device-related thrombus (DRT) has emerged as a clinically relevant complication that directly compromises the protective intent of LAAO. This comprehensive narrative review synthesizes contemporary evidence on the incidence, mechanisms, predictors, clinical impact, and management of DRT. DRT is a multifactorial phenomenon that carries an annual incidence ranging from 1.75% to almost 5%, resulting from the interplay between post-implant flow dynamics, device engineering, endothelialization processes, procedural factors, and patient-specific prothrombotic features. Accumulating data from observational registries links DRT to increased risks of ischemic stroke, systemic embolism, major adverse cardiovascular events (MACE), and mortality. Although evidence is growing, optimal management regimens for both the prevention and treatment of DRT remain undefined. Moreover, a lack of standardization also affects diagnosis and imaging surveillance, mainly performed by transesophageal echocardiography or cardiac computed tomography. By integrating mechanistic insights, clinical predictors, device-specific considerations, and therapeutic evidence, this review highlights current knowledge gaps and proposes practical considerations to inform individualized risk stratification, surveillance, and management of DRT in contemporary LAAO practice. Full article

Background: The global demographic shift towards an aging population has driven a steady, exponential increase in the utilization of cardiac implantable electronic devices (CIEDs). Consequently, device-related infectious complications have emerged as a leading cause of morbidity and healthcare expenditure. Patients in their eighth decade of life—octogenarians (aged 80–90 years)—represent an exceptionally high-risk demographic due to the compounding factors of physiological frailty, immunosenescence, and complex multi-morbidity. Despite this growing demographic, their specific clinical presentations, microbiological profiles, and procedural outcomes following infection remain poorly defined in the current literature. This study aimed to comprehensively compare the clinical characteristics, pathogen distribution, and in-hospital outcomes of CIED infections in an octogenarian cohort against a younger patient population. Methods: We conducted a robust retrospective cohort analysis of 383 consecutive patients treated for confirmed CIED infections at one major tertiary referral center (Heidelberg University Hospital) between January 2002 and December 2022. The cohort was stratified by age into octogenarians (n = 76) and a younger control group (n = 307). We systematically extracted and compared data regarding baseline clinical presentation, chronic comorbidities, detailed microbiological cultures (pocket, blood, and extracted leads), and definitive in-hospital outcomes, primarily mortality and length of stay. Results: The octogenarian cohort exhibited a significantly heavier comorbidity burden, notably higher rates of coronary artery disease (51.3% vs. 29.6%, p < 0.001), systemic hypertension (55.3% vs. 38.1%, p = 0.007), and chronic obstructive pulmonary disease (7.9% vs. 1.6%, p = 0.003). Furthermore, therapeutic systemic anticoagulant use was substantially more prevalent in the elderly group (60.5% vs. 45.0%, p = 0.015). Octogenarians presented overwhelmingly with localized generator pocket infections (73.0% vs. 30.0%, p < 0.001) but paradoxically also demonstrated higher rates of systemic bacteremia and sepsis (26.3% vs. 15.0%, p = 0.019). Microbiological analysis revealed a unique pathogen profile, with Staphylococcus capitis found with significantly higher frequency in the generator pockets of the elderly cohort. Remarkably, despite possessing a higher average lead burden (2.1 vs. 1.2 leads) and extreme comorbidity profiles, octogenarians demonstrated no statistically significant differences in in-hospital mortality (3.9% vs. 4.2%, p = 1.000) or overall length of hospital stay (14.7 vs. 17.2 days, p = 0.386) when compared to the younger cohort. Conclusions: Octogenarians suffering from CIED infections display highly distinct clinical and microbiological profiles, characterized predominantly by elevated rates of localized pocket infections, specific opportunistic pathogens, and a severe underlying comorbidity burden. Crucially, our findings indicate that with the application of modern extraction and management protocols, advanced age alone does not intrinsically correlate with increased in-hospital mortality. Future prevention and perioperative management strategies tailored to this rapidly expanding demographic must heavily prioritize the mitigation of pocket-related complications, particularly considering the high prevalence of concurrent anticoagulation therapy. Full article

Background: Atrial fibrillation (AF) remains the most common cardiac arrhythmia, with pulmonary vein isolation (PVI) established as the cornerstone of interventional treatment. However, in patients with persistent AF (PersAF), the success rates of PVI alone tend to be limited. A promising additional target is the left atrial appendage (LAA). In recent years, cryoballoon (CB) technology has become a tool for achieving durable PVI. Its application for LAAI has been investigated as a potentially advantageous alternative to radiofrequency ablation, and a positive effect on long-term outcome has been reported. However, the available data is limited. This study sought to investigate the clinical impact of CB-based LAAI in addition to PVI. Methods: This is a prospective, interventional, single-centre study. Consecutive patients with symptomatic PersAF were prospectively enrolled. In total 23 patients with PersAF underwent PVI plus LAAI using the CB system. Percutaneous LAA closure was performed within 2–3 months in all patients by implanting an endocardial LAA-closure device. Prior to LAA closure, LAAI durability was systematically assessed by invasive remapping studies. Results: A total of 100% of PVs were successfully isolated using the CB only (n = 91/91). Concerning LAAIs, a total of 21/23 (91%) remained isolated at the end of the procedure. After the ablation procedure including LAAI, all patients were scheduled for TEE assessment and LAA closure. TEE was performed after a mean of 54 ± 19 days. In 6/23 (26%) patients, LAA thrombus formation was detected after LAAI. A total of 23/23 patients (100%) received LAAC after a mean of 72 ± 45 days. Durability of LAAI was assessed utilizing a spiral mapping catheter in 23/23 patients (100%). In a total of 17/23 (74%) patients, durable LAA isolation was detected. Durable PVI of all PVs was detected in 16/23 (70%) patients. During a mean follow-up of 13 ± 3.4 months, stable sinus rhythm was maintained in 15 (65%) patients. The LAA showed reconnection in 3/23 (13%) patients, with arrhythmia recurrence. During follow-up, one stroke (318 days after LAAC) and one device thrombus (56 days after LAAC) occurred. Conclusions: While CB-based LAAI may offer benefits in managing persistent AF, it presents a significant risk of thrombus formation in the LAA, even with appropriate OAC. Early closure of the LAA following LAAI appears promising in mitigating these risks, but further evidence is needed to establish clear best practices. Full article

Myocardial infarction (MI) is one of the prevalent cardiovascular diseases, which is caused by obstruction of one or more coronary arteries, leading to cardiac tissue ischemia and death. One of the main consequences of MI is heart failure, which is defined as dysfunction of the heart muscle to pump blood into peripheral organs. Cardiac patches have drawn a lot of interest as a potentially effective way to restore damaged cardiac tissue and enhance its functionality. They are polymer-based scaffolds designed to be implanted on the heart surface, and they have shown a significant therapeutic effect in the treatment of MI by improving cardiac function and providing mechanical support for the infarction site by the delivery of various bioactive substances or cells. Several biomaterials with specific mechanical and chemical characteristics have been widely used as a scaffold in the process of fabricating cardiac patches. In this study, we focus on the latest developments in the manufacturing of synthetic-polymer-based cardiac patches used to treat heart failure induced by myocardial infarction. We describe the mechanical and chemical characteristics of several synthetic polymers and highlight the main benefits and drawbacks of each type. An overview of the major challenges and the future development directions in the field of cardiac patches is also highlighted. Full article

Background: Infective endocarditis (IE) affects both native and prosthetic heart valves, the endocardial surface, as well as cardiac implantable electronic devices. Identifying specific IE biomarkers for its early risk stratification remains crucial, particularly in cases with blood culture-negative endocarditis. Methods: Eleven native heart valves obtained from IE and calcific aortic valve disease (CAVD) patients were analyzed. Immunohistochemical analysis of a pan-leukocyte marker (CD45), macrophage marker (CD68), T-lymphocyte marker (CD3), B-lymphocyte marker (CD19), neutrophil myeloperoxidase (MPO), and marker of vascular endothelial cells (CD31) was performed. Differentially expressed genes (DEGs) were identified by whole-transcriptome sequencing; proteomic profiling was performed by dot-blotting. Results: The immunophenotyping demonstrates the infiltration of macrophages and neutrophils, as well as occasional T-lymphocytes in the IE-affected aortic valves, and the CAVD-affected heart valves were characterized by the absence of neutrophils. For the whole-transcriptome sequencing, 157 DEGs were identified: 124 DEGs were upregulated, and 33 genes were downregulated in the IE-affected heart valves compared to the CAVD-affected ones. According to the dot-blotting, 35 cytokines were identified in the studied heart valves, but only 21 molecules were expressed in both IE and CAVD-affected heart valves. Analysis of proteases and their inhibitors allowed the identification of 13 protease molecules and 18 enzyme inhibitor molecules in all examined heart valves. Conclusions: The results of the present study can help to improve our understanding of the IE pathogenesis. In addition, we identified the candidate cellular and molecular-genetic features of IE-affected native heart valves. Full article

Advances in implantable and wearable cardiac monitoring technologies have led to widespread detection of brief, often asymptomatic atrial high-rate episodes, frequently labelled as device-detected atrial fibrillation (AF). While detection has increased substantially, the clinical interpretation of these findings remains uncertain. Observational studies demonstrate associations between AF burden and stroke risk but reveal marked inter-individual heterogeneity and no consistent temporal threshold below which risk is eliminated. Recent randomised controlled trials show that anticoagulation guided solely by arrhythmia duration confers limited net clinical benefit, with modest reductions in ischaemic stroke offset by increased bleeding. These findings challenge the biological and clinical validity of rigid time-based thresholds for intervention. Increasing evidence suggests that AF may act primarily as a marker of underlying atrial disease rather than the sole mechanistic cause of thromboembolism. This article provides an evidence-informed perspective on the interpretation of device-detected AF in contemporary clinical practice and argues for a shift away from duration-based triggers toward a longitudinal, risk-adapted approach that integrates AF trajectory, atrial substrate, and clinical context. Emerging tools such as artificial intelligence-enhanced electrocardiography may help identify occult atrial pathology but must augment rather than replace clinical judgement. Proportionate, individualised care should supersede reflexive treatment strategies in the management of device-detected AF. Full article

Background: The aim of this study is to determine the safety of a locally implemented Standard of Practice (SOP) in patients with cardiac implantable electronic devices (CIEDs). With increasing use of radiotherapy in cancer treatment and the widespread adaptation of CIEDs, the British Heart Rhythm Society introduced new guidance in 2025. There remains ambiguity between various international, as well as manufacturer, guidelines on the management of these patients. Methods: This was a retrospective single-centre observational study analysing patients with CIEDs receiving radiotherapy after the implementation of our Standard of Practice in 2021. Patients were identified using the Cardiobase system. Patients were divided into non-pacemaker-dependent, pacemaker-dependent and implantable-cardioverter–defibrillator (ICD) groups. Lead sensing and impedance values were gathered pre- and post-treatment and analysed using a paired Student’s T-test. Results: A total of 320 patients were included in this study. There were no statistically significant changes in lead sensing capabilities in any of the groups pre- and post-radiotherapy with a p value of >0.05. There were no statistically significant changes in lead impedance in the ICD and non-pacemaker-dependent groups. Although statistically significant (p = 0.039), there was no clinically significant reduction in atrial lead impedance in the pacemaker-dependent cohort. Conclusions: From the obtained results, we can conclude that our locally implemented SOP is a safe alternative to BHRS guidelines. Full article

Large animal models are a critical component of the preclinical evaluation of mechanical cardiac implants, enabling assessment of safety and performance under physiological conditions that cannot be adequately reproduced in vitro. Choosing a suitable animal model is important for both scientifically valid and ethically responsible preclinical evaluation. However, interspecies differences between animal models and humans pose significant challenges for relevant translation of preclinical findings to clinical outcomes. This narrative review provides a comprehensive overview of commonly used large animal models (sheep, goats, pigs, and calves) for the preclinical assessment of mechanical cardiac implants, including prosthetic heart valves, ventricular assist devices, and total artificial hearts. We summarize key anatomical and physiological characteristics that influence device implantation, chronic follow-up, and translational value. Emphasis is placed on three critical outcome domains for preclinical evaluation of mechanical cardiac implants: calcification, thrombogenicity, and hemodynamic performance. Species- and age-dependent differences in calcification are reviewed, identifying juvenile sheep as a worst-case model for early manifestation and detection of graft mineralization. Interspecies differences in coagulation biology are examined, showing attenuated platelet responses in sheep and closer similarity between porcine and human platelet behavior, supporting pigs as the preferred thrombogenicity model. Hemodynamic evaluation strategies in acute and chronic large-animal studies are discussed, with particular emphasis on circulatory demands influenced by somatic growth and on device adaptability under varying loading conditions. Overall, this review provides practical, outcome-driven guidance for large animal model selection and experimental design in mechanical cardiac implant research, while identifying key limitations, knowledge gaps, and the need for standardized reporting to improve the translational reliability of preclinical studies. Based on the findings presented in this review, we conclude that there is no single animal model capable of evaluating all relevant aspects of a device. Instead, different animal models provide distinct advantages depending on the outcomes of interest. Full article