Temporal changes in CT-derived fractional flow reserve in patients after heart transplantation.

BACKGROUND: Adding functional information by CT-derived fractional flow reserve (FFRct) to coronary CT angiography (CCTA) and assessing its temporal change may provide insight into the natural history and physiopathology of cardiac allograft vasculopathy (CAV) in heart transplantation (HTx) patients. We assessed FFRct changes as well as CAV progression over a 2-year period in HTx patients undergoing serial CT imaging. METHODS: HTx patients from Erasmus MC and Mount Sinai Hospital, who had consecutive CCTAs 2 years apart were evaluated. FFRct analysis was performed for both scans. FFRct values at the most distal point in the left anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA) were measured after precisely matching the anatomical locations in both analyses. Also, the number of anatomical coronary stenoses of > 30% was scored. RESULTS: In total, 106 patients (median age 57 [interquartile range 47-67] years, 67% male) at 9 [6-13] years after HTx at the time of the baseline CCTA were included. Median distal FFRct values significantly decreased from baseline to follow-up for the LAD from 0.85 [0.79-0.90] to 0.84 [0.76-0.90] (p = 0.001), LCX from 0.92 [0.88-0.96] to 0.91 [0.85-0.95] (p = 0.009), and RCA from 0.92 [0.86-0.95] to 0.90 [0.86-0.94] (p = 0.004). The number of focal anatomical stenoses of > 30% increased from a median of 1 [0-2] at baseline to 2 [0-3] at follow-up (p = 0.009). CONCLUSIONS: The distal coronary FFRct values in post-HTX patients in each of the three major coronary arteries decreased, and the number of focal coronary stenoses increased over a 2-year period. Temporal FFRct change rate may become an additional parameter in the follow-up of HTx patients, but more research is needed to elucidate its role. CLINICAL RELEVANCE STATEMENT: CT-derived fractional flow reserve (FFRct) is important post-heart transplant because of additional information on coronary CT angiography for cardiac allograft vasculopathy (CAV) detection. The decrease and degree of reduction in distal FFRct value may indicate progression in anatomic CAV burden. KEY POINTS: CT-derived fractional flow reserve (FFRct) is important for monitoring cardiac allograft vasculopathy (CAV) in heart transplant patients. Over time, transplant patients showed a decrease in distal FFRct and an increase in coronary stenoses. Temporal changes in FFRct could be crucial for transplant follow-up, aiding in CAV detection.

Epicardial fat volume is related to the degree of cardiac allograft vasculopathy.

OBJECTIVES: Increasing evidence suggests a role for epicardial fat in the development of coronary artery disease in the general population. Heart transplantation patients are at increased risk of developing a specific form of coronary artery disease, cardiac allograft vasculopathy (CAV), which has far-reaching consequences in terms of morbidity and mortality. Until now, the role of epicardial fat volume (EFV) in the development of CAV remains unknown. Hence, we investigated the relationship between EFV and CAV as well as the influence of donor/recipient sex on EFV. METHODS: Adult heart transplant patients who underwent coronary computed tomography angiography (CCTA) for CAV screening who were four or more years post-HT were included. Using the CT examinations, we quantified the EFV and the degree of CAV. Ordinal and linear regression models were used to assess the association of EFV with CAV. RESULTS: In total, 149 (median age 44.5 years, 36% women) patients were included. The median time between HT and the CT scan was 11.0 (7.3-16.1) years. CAV grade 0, 1, 2 and 3 were seen in 85 (57%), 32 (22%), 14 (9%), and 18 (12%) patients, respectively. The median EFV was 208.4 (128.9-276.0) mL. Larger EFV were related to higher degrees of CAV (median of 164.7 to 290.6 mL for CAV grade 0 and 3, respectively, OR 5.23 (2.47-11.06), p < 0.001). Male recipients had significantly more EFV than female recipients irrespective of the donor sex (232.7 mL vs. 147.2 mL respectively, p < 0.001). Determinants for EFV were recipient sex, number of rejections, donor age, time between HT and CT scan, recipient BMI, and diabetes mellitus. CONCLUSIONS: EFV was associated with higher degrees of CAV. The recipient sex influenced the EFV more than the donor sex. KEY POINTS: • Patients after heart transplantation have a high amount of epicardial fat while larger amounts of epicardial fat are related to higher grades of cardiac allograft vasculopathy. • Determinants of higher epicardial fat volume included recipient sex, number of rejections, donor age, time between HT and CT scan, recipient BMI, and diabetes mellitus. • Longitudinal studies are needed to further disentangle the role of epicardial fat in the development and progression of cardiac allograft vasculopathy. Demonstration of four patients (from CAV grade 0 to CAV grade 3) in whom epicardial fat volume was determined. In red, the voxels identified as epicardial fat.

Mapping-guided atrial lead placement determines optimal conduction across Bachmann's bundle: a rationale for patient-tailored pacing therapy.

AIMS: Conventional right atrial appendage (RAA) pacing is associated with increased atrial activation time resulting in higher incidences of atrial tachyarrhythmia. Optimal pacing sites ideally shorten inter-atrial conduction delay, thereby decreasing atrial excitation time. We therefore examined the impact of programmed electrical stimulation (PES) from the right atrium (RA) and left atrium (LA) on the electrophysiological properties of Bachmann's bundle (BB). METHODS AND RESULTS: High-resolution epicardial mapping of BB was performed during sinus rhythm (SR) and PES in 34 patients undergoing cardiac surgery. Programmed electrical stimulation was performed from the RAA, junction of the RA with inferior caval vein (LRA), and left atrial appendage (LAA). Pacing from either the RAA or LAA resulted in, respectively, right- and left-sided conduction across BB. However, during LRA pacing in most patients (n = 15), activation started in the centre of BB. The total activation time (TAT) of BB during RAA pacing [63 (55-78) ms] was similar to that of SR [61 (52-68) ms, P = 0.464], while it decreased during LRA [45 (39-62) ms, P = 0.003] and increased during LAA pacing [67 (61-75) ms, P = 0.009]. Reduction of both conduction disorders and TAT was most often achieved during LRA pacing (N = 13), especially in patients who already had a higher amount of conduction disorders during SR [9.8 (7.3-12.3) vs. 4.5 (3.5-6.6)%, P < 0.001]. CONCLUSION: Pacing from the LRA results in a remarkable decrease of TAT compared with pacing from the LAA or RAA. As the most optimal pacing site varies between patients, individualized positioning of the atrial pacing lead guided by mapping of BB may be one of the new frontiers for atrial pacing.

Atrial extrasystoles enhance low-voltage fractionation electrograms in patients with atrial fibrillation.

BACKGROUND AND AIMS: Atrial extrasystoles (AES) provoke conduction disorders and may trigger episodes of atrial fibrillation (AF). However, the direction- and rate-dependency of electrophysiological tissue properties on epicardial unipolar electrogram (EGM) morphology is unknown. Therefore, this study examined the impact of spontaneous AES on potential amplitude, -fractionation, -duration, and low-voltage areas (LVAs), and correlated these differences with various degrees of prematurity and aberrancy. METHODS AND RESULTS: Intra-operative high-resolution epicardial mapping of the right and left atrium, Bachmann's Bundle, and pulmonary vein area was performed during sinus rhythm (SR) in 287 patients (60 with AF). AES were categorized according to their prematurity index (>25% shortening) and degree of aberrancy (none, mild/opposite, moderate and severe). In total, 837 unique AES (457 premature; 58 mild/opposite, 355 moderate, and 154 severe aberrant) were included. The average prematurity index was 28% [12-45]. Comparing SR and AES, average voltage decreased (-1.1 [-1.2, -0.9] mV, P < 0.001) at all atrial regions, whereas the amount of LVAs and fractionation increased (respectively, +3.4 [2.7, 4.1] % and +3.2 [2.6, 3.7] %, P < 0.001). Only weak or moderate correlations were found between EGM morphology parameters and prematurity indices (R2 < 0.299, P < 0.001). All parameters were, however, most severely affected by either mild/opposite or severely aberrant AES, in which the effect was more pronounced in AF patients. Also, there were considerable regional differences in effects provoked by AES. CONCLUSION: Unipolar EGM characteristics during spontaneous AES are mainly directional-dependent and not rate-dependent. AF patients have more direction-dependent conduction disorders, indicating enhanced non-uniform anisotropy that is uncovered by spontaneous AES.

Premature atrial contractions promote local directional heterogeneities in conduction velocity vectors.

AIMS: Loss of cell-to-cell communication results in local conduction disorders and directional heterogeneity (LDH) in conduction velocity (CV) vectors, which may be unmasked by premature atrial contractions (PACs). We quantified LDH and examined differences between sinus rhythm (SR) and spontaneous PACs in patients with and without atrial fibrillation (AF). METHODS AND RESULTS: Intra-operative epicardial mapping of the right and left atrium (RA, LA), Bachmann's bundle (BB) and pulmonary vein area (PVA) was performed in 228 patients (54 with AF). Conduction velocity vectors were computed at each electrode using discrete velocity vectors. Directions and magnitudes of individual vectors were compared with surrounding vectors to identify LDH. Five hundred and three PACs [2 (1-3) per patient; prematurity index of 45 ± 12%] were included. During SR, most LDH were found at BB and LA [11.9 (8.3-14.9) % and 11.3 (8.0-15.2) %] and CV was lowest at BB [83.5 (72.4-94.3) cm/s, all P < 0.05]. Compared with SR, the largest increase in LDH during PAC was found at BB and PVA [+13.0 (7.7, 18.3) % and +12.5 (10.8, 14.2) %, P < 0.001]; CV decreased particularly at BB, PVA and LA [-10.0 (-13.2, -6.9) cm/s, -9.3 (-12.5, -6.2) cm/s and -9.1 (-11.7, -6.6) cm/s, P < 0.001]. Comparing patients with and without AF, more LDH were found during SR in AF patients at PVA and BB, although the increase in LDH during PACs was similar for all sites. CONCLUSION: Local directional heterogeneity is a novel methodology to quantify local heterogeneity in CV as a possible indicator of electropathology. Intra-operative high-resolution mapping indeed revealed that LDH increased during PACs particularly at BB and PVA. Also, patients with AF already have more LDH during SR, which becomes more pronounced during PACs.

Characterization of unipolar electrogram morphology: a novel tool for quantifying conduction inhomogeneity.

AIMS: Areas of conduction inhomogeneity (CI) during sinus rhythm may facilitate the initiation and perpetuation of atrial fibrillation (AF). Currently, no tool is available to quantify the severity of CI. Our aim is to develop and validate a novel tool using unipolar electrograms (EGMs) only to quantify the severity of CI in the atria. METHODS AND RESULTS: Epicardial mapping of the right atrium (RA) and left atrium, including Bachmann's bundle, was performed in 235 patients undergoing coronary artery bypass grafting surgery. Conduction inhomogeneity was defined as the amount of conduction block. Electrograms were classified as single, short, long double (LDP), and fractionated potentials (FPs), and the fractionation duration of non-single potentials was measured. The proportion of low-voltage areas (LVAs, <1 mV) was calculated. Increased CI was associated with decreased potential voltages and increased LVAs, LDPs, and FPs. The Electrical Fingerprint Score consisting of RA EGM features, including LVAs and LDPs, was most accurate in predicting CI severity. The RA Electrical Fingerprint Score demonstrated the highest correlation with the amount of CI in both atria (r = 0.70, P < 0.001). CONCLUSION: The Electrical Fingerprint Score is a novel tool to quantify the severity of CI using only unipolar EGM characteristics recorded. This tool can be used to stage the degree of conduction abnormalities without constructing spatial activation patterns, potentially enabling early identification of patients at high risk of post-operative AF or selection of the appropriate ablation approach in addition to pulmonary vein isolation at the electrophysiology laboratory.

Acute Biomechanical Effects of Empagliflozin on Living Isolated Human Heart Failure Myocardium.

PURPOSE: Multiple randomized controlled trials have presented SGLT2 inhibitors (SGLT2i) as novel pharmacological therapy for patients with heart failure, resulting in reductions in hospitalization for heart failure and mortality. Given the absence of SGLT2 receptors in the heart, mechanisms of direct cardioprotective effects of SGLT2i are complex and remain to be investigated. In this study, we evaluated the direct biomechanical effects of SGLT2i empagliflozin on isolated myocardium from end-stage heart failure patients. METHODS: Ventricular tissue biopsies obtained from 7 patients undergoing heart transplantation or ventricular assist device implantation surgery were cut into 27 living myocardial slices (LMS) and mounted in custom-made cultivation chambers with mechanical preload and electrical stimulation, resulting in cardiac contractions. These 300 µm thick LMS were subjected to 10 µM empagliflozin and with continuous recording of biomechanical parameters. RESULTS: Empagliflozin did not affect the maximum contraction force of the slices, however, increased total contraction duration by 13% (p = 0.002) which was determined by prolonged time to peak and time to relaxation (p = 0.009 and p = 0.003, respectively). CONCLUSION: The addition of empagliflozin to LMS from end-stage heart failure patients cultured in a biomimetic system improves contraction and relaxation kinetics by increasing total contraction duration without diminishing maximum force production. Therefore, we present convincing evidence that SGLT2i can directly act on the myocardium in absence of systemic influences from other organ systems.

The current status of stem cell-based therapies during ex vivo graft perfusion: An integrated review of four organs.

The use of extended criteria donor grafts is a promising strategy to increase the number of organ transplantations and reduce waitlist mortality. However, these organs are often compromised and/or damaged, are more susceptible to preservation injury, and are at risk for developing post-transplant complications. Ex vivo organ perfusion is a novel technology to preserve donor organs while providing oxygen and nutrients at distinct perfusion temperatures. This preservation method allows to resuscitate grafts and optimize function with therapeutic interventions prior to solid organ transplantation. Stem cell-based therapies are increasingly explored for their ability to promote regeneration and reduce the inflammatory response associated with in vivo reperfusion. The aim of this review is to describe the current state of stem cell-based therapies during ex vivo organ perfusion for the kidney, liver, lung, and heart. We discuss different strategies, including type of cells, route of administration, mechanisms of action, efficacy, and safety. The progress made within lung transplantation justifies the initiation of clinical trials, whereas more research is likely required for the kidney, liver, and heart to progress into clinical application. We emphasize the need for standardization of methodology to increase comparability between future (clinical) studies.

Oral Glucose Tolerance Test for the Screening of Glucose Intolerance Long Term Post-Heart Transplantation.

Post-transplant diabetes mellitus (PTDM) is a frequent complication post-heart transplantation (HT), however long-term prevalence studies are missing. The aim of this study was to determine the prevalence and determinants of PTDM as well as prediabetes long-term post-HT using oral glucose tolerance tests (OGTT). Also, the additional value of OGTT compared to fasting glucose and glycated hemoglobin (HbA1c) was investigated. All patients > 1 year post-HT seen at the outpatient clinic between August 2018 and April 2021 were screened with an OGTT. Patients with known diabetes, an active infection/rejection/malignancy or patients unwilling or unable to undergo OGTT were excluded. In total, 263 patients were screened, 108 were excluded. The included 155 patients had a median age of 54.3 [42.2-64.3] years, and 63 (41%) were female. Median time since HT was 8.5 [4.8-14.5] years. Overall, 51 (33%) had a normal range, 85 (55%) had a prediabetes range and 19 (12%) had a PTDM range test. OGTT identified prediabetes and PTDM in more patients (18% and 50%, respectively), than fasting glucose levels and HbA1c. Age at HT (OR 1.03 (1.00-1.06), p = 0.044) was a significant determinant of an abnormal OGTT. Prediabetes as well as PTDM are frequently seen long-term post-HT. OGTT is the preferred screening method.

Vagus Nerve Stimulation and Atrial Fibrillation: Revealing the Paradox.

BACKGROUND AND OBJECTIVE: The cardiac autonomic nervous system (CANS) plays an important role in the pathophysiology of atrial fibrillation (AF). Cardiovascular disease can cause an imbalance within the CANS, which may contribute to the initiation and maintenance of AF. Increased understanding of neuromodulation of the CANS has resulted in novel emerging therapies to treat cardiac arrhythmias by targeting different circuits of the CANS. Regarding AF, neuromodulation therapies targeting the vagus nerve have yielded promising outcomes. However, targeting the vagus nerve can be both pro-arrhythmogenic and anti-arrhythmogenic. Currently, these opposing effects of vagus nerve stimulation (VNS) have not been clearly described. The aim of this review is therefore to discuss both pro-arrhythmogenic and anti-arrhythmogenic effects of VNS and recent advances in clinical practice and to provide future perspectives for VNS to treat AF. MATERIALS AND METHODS: A comprehensive review of current literature on VNS and its pro-arrhythmogenic and anti-arrhythmogenic effects on atrial tissue was performed. Both experimental and clinical studies are reviewed and discussed separately. RESULTS: VNS exhibits both pro-arrhythmogenic and anti-arrhythmogenic effects. The anatomical site and stimulation settings during VNS play a crucial role in determining its effect on cardiac electrophysiology. Since the last decade, there is accumulating evidence from experimental studies and randomized clinical studies that low-level VNS (LLVNS), below the bradycardia threshold, is an effective treatment for AF. CONCLUSION: LLVNS is a promising novel therapeutic modality to treat AF and further research will further elucidate the underlying anti-arrhythmogenic mechanisms, optimal stimulation settings, and site to apply LLVNS.

Atrial electrophysiological characteristics of aging.

INTRODUCTION: Advancing age is a known risk factor for developing atrial fibrillation (AF), yet it is unknown which electrophysiological changes contribute to this increased susceptibility. The goal of this study is to investigate conduction disturbances and unipolar voltages (UV) related to aging. METHODS: We included 216 patients (182 male, age: 36-83 years) without a history of AF undergoing elective coronary artery bypass surgery. Five seconds of sinus rhythm were recorded intraoperatively at the right atrium (RA), Bachmann's bundle (BB), the left atrium and the pulmonary vein area (PVA). Conduction delay (CD), -block (CB), -velocity (CV), length of longest CB lines and UV were assessed in all regions. RESULTS: With aging, increasing conduction disturbances were found, particularly at RA and BB (RA: longest CB line rs = .158, p = .021; BB: CB prevalence rs = .206, p = .003; CV rs = -.239, p < .0005). Prevalence of low UV areas (UV <5th percentile) increased with aging at the BB and PVA (BB: rs = .237, p < .0005 and PVA: rs = .228, p = .001). CONCLUSIONS: Aging is accompanied by an increase in conduction disturbances during sinus rhythm and a higher prevalence of low UV areas, particularly at BB and in the RA. These electrophysiological alterations could in part explain the increasing susceptibility to AF development associated with aging.

Right ventricular phenotype, function, and failure: a journey from evolution to clinics.

The right ventricle has long been perceived as the "low pressure bystander" of the left ventricle. Although the structure consists of, at first glance, the same cardiomyocytes as the left ventricle, it is in fact derived from a different set of precursor cells and has a complex three-dimensional anatomy and a very distinct contraction pattern. Mechanisms of right ventricular failure, its detection and follow-up, and more specific different responses to pressure versus volume overload are still incompletely understood. In order to fully comprehend right ventricular form and function, evolutionary biological entities that have led to the specifics of right ventricular physiology and morphology need to be addressed. Processes responsible for cardiac formation are based on very ancient cardiac lineages and within the first few weeks of fetal life, the human heart seems to repeat cardiac evolution. Furthermore, it appears that most cardiogenic signal pathways (if not all) act in combination with tissue-specific transcriptional cofactors to exert inductive responses reflecting an important expansion of ancestral regulatory genes throughout evolution and eventually cardiac complexity. Such molecular entities result in specific biomechanics of the RV that differs from that of the left ventricle. It is clear that sole descriptions of right ventricular contraction patterns (and LV contraction patterns for that matter) are futile and need to be addressed into a bigger multilayer three-dimensional picture. Therefore, we aim to present a complete picture from evolution, formation, and clinical presentation of right ventricular (mal)adaptation and failure on a molecular, cellular, biomechanical, and (patho)anatomical basis.

Identification of local atrial conduction heterogeneities using high-density conduction velocity estimation.

AIMS: Accurate determination of intra-atrial conduction velocity (CV) is essential to identify arrhythmogenic areas. The most optimal, commonly used, estimation methodology to measure conduction heterogeneity, including finite differences (FiD), polynomial surface fitting (PSF), and a novel technique using discrete velocity vectors (DVV), has not been determined. We aim (i) to identify the most suitable methodology to unravel local areas of conduction heterogeneities using high-density CV estimation techniques, (ii) to quantify intra-atrial differences in CV, and (iii) to localize areas of CV slowing associated with paroxysmal atrial fibrillation (PAF). METHODS AND RESULTS: Intra-operative epicardial mapping (>5000 sites, interelectrode distances 2 mm) of the right and left atrium and Bachmann's bundle (BB) was performed during sinus rhythm (SR) in 412 patients with or without PAF. The median atrial CV estimated using the DVV, PSF, and FiD techniques was 90.0 (62.4-116.8), 92.0 (70.6-123.2), and 89.4 (62.5-126.5) cm/s, respectively. The largest difference in CV estimates was found between PSF and DVV which was caused by smaller CV magnitudes detected only by the DVV technique. Using DVV, a lower CV at BB was found in PAF patients compared with those without atrial fibrillation (AF) [79.1 (72.2-91.2) vs. 88.3 (79.3-97.2) cm/s; P < 0.001]. CONCLUSIONS: Areas of local conduction heterogeneities were most accurately identified using the DVV technique, whereas PSF and FiD techniques smoothen wavefront propagation thereby masking local areas of conduction slowing. Comparing patients with and without AF, slower wavefront propagation during SR was found at BB in PAF patients, indicating structural remodelling.

Classification of sinus rhythm single potential morphology in patients with mitral valve disease.

AIMS: The morphology of unipolar single potentials (SPs) contains information on intra-atrial conduction disorders and possibly the substrate underlying atrial fibrillation (AF). This study examined the impact of AF episodes on features of SP morphology during sinus rhythm (SR) in patients with mitral valve disease. METHODS AND RESULTS: Intraoperative epicardial mapping (interelectrode distance 2 mm) of the right and left atrium (RA, LA), Bachmann's bundle (BB), and pulmonary vein area (PVA) was performed in 67 patients (27 male, 67 ± 11 years) with or without a history of paroxysmal AF (PAF). Unipolar SPs were classified according to their differences in relative R- and S-wave amplitude ratios. A clear predominance of S-waves was observed at BB and the RA in both the no AF and PAF groups (BB 88.8% vs. 85.9%, RA 92.1% vs. 85.1%, respectively). Potential voltages at the RA, BB, and PVA were significantly lower in the PAF group (P < 0.001 for each) and were mainly determined by the size of the S-waves amplitudes. The largest difference in S-wave amplitudes was found at BB; the S-wave amplitude was lower in the PAF group [4.08 (2.45-6.13) mV vs. 2.94 (1.40-4.75) mV; P < 0.001]. In addition, conduction velocity (CV) at BB was lower as well [0.97 (0.70-1.21) m/s vs. 0.89 (0.62-1.16) m/s, P < 0.001]. CONCLUSION: Though excitation of the atria during SR is heterogeneously disrupted, a history of AF is characterized by decreased SP amplitudes at BB due to loss of S-wave amplitudes and decreased CV. This suggests that SP morphology could provide additional information on wavefront propagation.

A novel diagnostic tool to identify atrial endo-epicardial asynchrony using signal fingerprinting.

OBJECTIVE: Patients with persistent atrial fibrillation (AF) have more electrical endo-epicardial asynchrony (EEA) during sinus rhythm (SR) than patients without AF. Prior mapping studies indicated that particularly unipolar, endo- and/or epicardial electrogram (EGM) morphology may be indicators of EEA. This study aim to develop a novel method for estimating the degree of EEA by using unipolar EGM characteristics recorded from either the endo- and/or epicardium. METHODS: Simultaneous endo-epicardial mapping during sinus rhythm was performed in 86 patients. EGM characteristics, including unipolar voltages, low-voltage areas (LVAs), potential types (single, short/long double and fractionated potentials: SP, SDP, LDP and FP) and fractionation duration (FD) of double potentials (DP) and FP were compared between EEA and non-EEA areas. Asynchrony Fingerprinting Scores (AFS) containing quantified EGM characteristics were constructed to estimate the degree of EEA. RESULTS: Endo- and epicardial sites of EEA areas are characterized by lower unipolar voltages, a higher number of LDPs and FPs and longer DP and FP durations. Patients with AF have lower potential voltages in EEA areas, along with alterations in the potential types. The EE-AFS, containing the proportion of endocardial LVAs and FD of epicardial DPs, had the highest predictive value for determining the degree of EEA (AUC: 0.913). Endo- and epi-AFS separately also showed good predictive values (AUC: 0.901 and 0.830 respectively). CONCLUSIONS: EGM characteristics can be used to identify EEA areas. AFS can be utilized as a novel diagnostic tool for accurately estimating the degree of EEA. These characteristics potentially indicate AF related arrhythmogenic substrates.

Preclinical Models of Cardiac Disease: A Comprehensive Overview for Clinical Scientists.

For recent decades, cardiac diseases have been the leading cause of death and morbidity worldwide. Despite significant achievements in their management, profound understanding of disease progression is limited. The lack of biologically relevant and robust preclinical disease models that truly grasp the molecular underpinnings of cardiac disease and its pathophysiology attributes to this stagnation, as well as the insufficiency of platforms that effectively explore novel therapeutic avenues. The area of fundamental and translational cardiac research has therefore gained wide interest of scientists in the clinical field, while the landscape has rapidly evolved towards an elaborate array of research modalities, characterized by diverse and distinctive traits. As a consequence, current literature lacks an intelligible and complete overview aimed at clinical scientists that focuses on selecting the optimal platform for translational research questions. In this review, we present an elaborate overview of current in vitro, ex vivo, in vivo and in silico platforms that model cardiac health and disease, delineating their main benefits and drawbacks, innovative prospects, and foremost fields of application in the scope of clinical research incentives.

Conduction Velocity and Anisotropic Properties of Fibrillation Waves During Acutely Induced and Long-Standing Persistent AF.

BACKGROUND: Quantified features of local conduction heterogeneity due to pathological alterations of myocardial tissue could serve as a marker for the degree of electrical remodeling and hence be used to determine the stage of atrial fibrillation (AF). OBJECTIVES: In this study, the authors investigated whether local directional heterogeneity (LDH) and anisotropy ratio, derived from estimated local conduction velocities (CVs) during AF, are suitable electrical parameters to stage AF. METHODS: Epicardial mapping (244-electrode array, interelectrode distance 2.25 mm) of the right atrium was performed during acute atrial fibrillation (AAF) (n = 25, 32 ± 11 years of age) and during long-standing persistent atrial fibrillation (LSPAF) (n = 23, 64 ± 9 years of age). Episodes of 9 ± 4 seconds of AF were analyzed. Local CV vectors were constructed to assess the degree of anisotropy. Directions and magnitudes of individual vectors were compared with surrounding vectors to identify LDH. RESULTS: Compared with the entire AAF group, LSPAF was characterized by slower conduction (71.5 ± 6.8 cm/s vs 67.6 ± 5.6 cm/s; P = 0.037) with a larger dispersion (1.59 ± 0.21 vs 1.95 ± 0.17; P < 0.001) and temporal variability (32.0 ± 4.7 cm/s vs 38.5 ± 3.3 cm/s; P < 0.001). Also, LSPAF was characterized by more LDH (19.6% ± 4.4% vs 26.0% ± 3.4%; P < 0.001) and a higher degree of anisotropy (1.38 ± 0.07 vs 1.51 ± 0.14; P < 0.001). Compared with the most complex type of AAF (type III), LSPAF was still associated with a larger CV dispersion, higher temporal variability of CV, and larger amount of LDH. CONCLUSIONS: Increasing AF complexity was associated with increased spatiotemporal variability of local CV vectors, local conduction heterogeneity, and anisotropy ratio. By using these novel parameters, LSPAF could potentially be discriminated from the most complex type of AAF. These observations may indicate pathological alterations of myocardial tissue underlying progression of AF.