Epicardial adipose tissue volume and density are associated with heart failure with improved ejection fraction.

BACKGROUND: Heart failure (HF) with improved ejection fraction (EF, HFimpEF) is a distinct HF subtype, characterized by left ventricular (LV) reverse remodeling and myocardial functional recovery. Multiple cardiometabolic factors are implicated in this process. Epicardial adipose tissue (EAT), emerging as an endocrine and paracrine organ, contributes to the onset and progression of HF. However, the relation between EAT and the incidence of HFimpEF is still unclear. METHODS: A total of 203 hospitalized HF patients with reduced EF (HFrEF, LVEF ≤ 40%) who underwent coronary CT angiography (CCTA) during index hospitalization were consecutively enrolled between November 2011 and December 2022. Routine follow-up and repeat echocardiograms were performed. The incidence of HFimpEF was defined as (1) an absolute LVEF improvement ≥ 10% and (2) a second LVEF > 40% (at least 3 months apart). EAT volume and density were semiautomatically quantified on non-enhanced series of CCTA scans. RESULTS: During a median follow-up of 8.6 (4.9 ~ 13.3) months, 104 (51.2%) patients developed HFimpEF. Compared with HFrEF patients, HFimpEF patients had lower EAT volume (115.36 [IQR 87.08 ~ 154.78] mL vs. 169.67 [IQR 137.22 ~ 218.89] mL, P < 0.001) and higher EAT density (-74.92 ± 6.84 HU vs. -78.76 ± 6.28 HU, P < 0.001). Multivariate analysis showed lower EAT volume (OR: 0.885 [95%CI 0.822 ~ 0.947]) and higher density (OR: 1.845 [95%CI 1.023 ~ 3.437]) were both independently associated with the incidence of HFimpEF. Subgroup analysis revealed that the association between EAT properties and HFimpEF was not modified by HF etiology. CONCLUSIONS: This study reveals that lower EAT volume and higher EAT density are associated with development of HFimpEF. Therapies targeted at reducing EAT quantity and improving its quality might provide favorable effects on myocardial recovery in HF patients.

A novel approach to terminate roof-dependent atrial flutter with epicardial conduction through septopulmonary bundle.

Atrial flutter, a prevalent cardiac arrhythmia, is primarily characterized by reentrant circuits in the right atrium. However, atypical forms of atrial flutter present distinct challenges in terms of diagnosis and treatment. In this study, we examine three noteworthy clinical cases of atypical atrial flutter, which offer compelling evidence indicating the implication of the lesser-known Septopulmonary Bundle (SPB). This inference is based on the identification of distinct electrocardiographic patterns observed in these patients and their favorable response to catheter ablation, which is a standard treatment for atrial flutter. Remarkably, in each case, targeted ablation at the anterior portion of the left atrial roof effectively terminated the arrhythmia, thus providing further support for the hypothesis of SPB involvement. These insightful observations shed light on the potential significance of the SPB in the etiology of atypical atrial flutter and introduce a promising therapeutic target. We anticipate that this paper will stimulate further exploration into the role of the SPB in atrial flutter and pave the way for the development of targeted ablation strategies.

Pericardium, epicardial adipose tissue, and heart failure with preserved ejection fraction: Pathophysiology, quantification and treatment target.

Heart failure is an important cause of mortality and morbidity worldwide. Heart failure with preserved ejection fraction (HFpEF) incidence and prevalence is increasing, and the phenotype associated with obesity is the most frequent. Epicardial adipose tissue (EAT) is directly associated with systemic obesity and several previous studies have shown a clear link between EAT and HFpEF. Moreover, the restriction induced by the pericardium is also linked to HFpEF. In this review we will describe the epidemiological association between the pericardium, EAT and HFpEF, how to quantify EAT, what are the pathophysiological mechanism to explain theses association and how can the pericardium and EAT be a treatment target in patients with HFpEF.

Road-Map to Epicardial Approach for Catheter Ablation of Ventricular Tachycardia in Structural Heart Disease: Results From a 10-Year Tertiary-Center Experience.

BACKGROUND: Epicardial approach in ventricular tachycardia (VT) ablation is still regarded as a second-step strategy, due to the risk of complications. We evaluated the frequency that epicardial ablation targets were identified and ablation performed following pericardial access compared with unnecessary pericardial access for different VT causes and potential markers of epicardial VT. METHODS: All VT ablation procedures including epicardial approach over a 10-year period were included. First-line epicardial approach was indicated in arrhythmogenic right ventricular cardiomyopathy (ARVC) and postmyocarditis VT; in patients with idiopathic dilated cardiomyopathy (IDCM) and postmyocardial infarction, indications resulted from available imaging techniques or 12-lead VT morphology. The epicardial approach was considered useful if epicardial ablation was performed after epicardial mapping. Feasibility, complications, and long-term outcome were reported. RESULTS: Four hundred and eighty-eight subjects with a median age of 60 years (interquartile range, 47-65) and of left ventricle ejection fraction 41% (interquartile range, 30-55) underwent 626 epicardial VT ablations. Percutaneous access had a success rate of 92.2% and a complication rate of 3.6%. Overall, epicardial approach was, respectively, indicated to 11.8% of postmyocardial infarction patients, 49.5% in IDCM, 94% in myocarditis, and 90.7% in ARVC. Epicardial ablation at the first ablation attempt was performed in 9.3% of postmyocardial infarction patients, 28.8% in IDCM, 86.5% in myocarditis, and 81.3% in patients with ARVC. In first-line epicardial group, ARVC and myocarditis showed the highest odds for epicardial ablation (OR, 4.057 [95% CI, 1.299-8.937]; P=0.007; OR, 3.971 [95% CI, 1.376-11.465]; P=0.005, respectively). IDCM independently predicted unnecessary epicardial approach (OR, 2.7 [95% CI, 1.7-4.3]; P<0.001). After a follow-up of 41 months (interquartile range, 19-64), patients with IDCM experienced higher rate of recurrences and mortality compared with other causes. CONCLUSIONS: Epicardial approach is integral part of ablation armamentarium regardless of the VT cause, with high feasibility and low complication rate in experienced centers. Our data support its use at first ablation attempt in VTs related to ARVC and myocarditis.

Preclinical Study of Pulsed Field Ablation of Difficult Ventricular Targets: Intracavitary Mobile Structures, Interventricular Septum, and Left Ventricular Free Wall.

BACKGROUND: Endocardial catheter-based pulsed field ablation (PFA) of the ventricular myocardium is promising. However, little is known about PFA's ability to target intracavitary structures, epicardium, and ways to achieve transmural lesions across thick ventricular tissue. METHODS: A lattice-tip catheter was used to deliver biphasic monopolar PFA to swine ventricles under general anesthesia, with electroanatomical mapping, fluoroscopy and intracardiac echocardiography guidance. We conducted experiments to assess the feasibility and safety of repetitive monopolar PFA applications to ablate (1) intracavitary papillary muscles and moderator bands, (2) epicardial targets, and (3) bipolar PFA for midmyocardial targets in the interventricular septum and left ventricular free wall. RESULTS: (1) Papillary muscles (n=13) were successfully ablated and then evaluated at 2, 7, and 21 days. Nine lesions with stable contact measured 18.3±2.4 mm long, 15.3±1.5 mm wide, and 5.8±1.0 mm deep at 2 days. Chronic lesions demonstrated preserved chordae without mitral regurgitation. Two targeted moderator bands were transmurally ablated without structural disruption. (2) Transatrial saline/carbon dioxide assisted epicardial access was obtained successfully and epicardial monopolar lesions had a mean length, width, and depth of 30.4±4.2, 23.5±4.1, and 9.1±1.9 mm, respectively. (3) Bipolar PFA lesions were delivered across the septum (n=11) and the left ventricular free wall (n=7). Twelve completed bipolar lesions had a mean length, width, and depth of 29.6±5.5, 21.0±7.3, and 14.3±4.7 mm, respectively. Chronically, these lesions demonstrated uniform fibrotic changes without tissue disruption. Bipolar lesions were significantly deeper than the monopolar epicardial lesions. CONCLUSIONS: This in vivo evaluation demonstrates that PFA can successfully ablate intracavitary structures and create deep epicardial lesions and transmural left ventricular lesions.

Rate of Change of Initial Intrinsicoid Deflection Predicts Endocardial Versus Epicardial Ventricular Tachycardia.

BACKGROUND: Assessment of origin of ventricular tachycardias (VTs) arising from epicardial vs endocardial sites are largely challenged by the available criteria and etiology of cardiomyopathy. Current electrocardiographic (ECG) criteria based on 12-lead ECG have varying sensitivity and specificity based on site of origin and etiology of cardiomyopathy. OBJECTIVES: This study sought to test the hypothesis that epicardial VT has a slower initial rate of depolarization than endocardial VT. METHODS: We developed a method that takes advantage of the fact that electrical conduction is faster through the cardiac conduction system than the myocardium, and that the conduction system is primarily an endocardial structure. The technique calculated the rate of change in the initial VT depolarization from a signal-averaged 12-lead ECG. We hypothesized that the rate of change of depolarization in endocardial VT would be faster than epicardial. We assessed by applying this technique among 26 patients with VT in nonischemic cardiomyopathy patients. RESULTS: When comparing patients with VTs ablated using epicardial and endocardial approaches, the rate of change of depolarization was found to be significantly slower in epicardial (6.3 ± 3.1 mV/s vs 11.4 ± 3.7 mV/s; P < 0.05). Statistical significance was found when averaging all 12 ECG leads and the limb leads, but not the precordial leads. Follow up analysis by calculation of a receiver-operating characteristic curve demonstrated that this analysis provides a strong prediction if a VT is epicardial in origin (AUC range 0.72-0.88). Slower rate of change of depolarization had high sensitivity and specificity for prediction of epicardial VT. CONCLUSIONS: This study demonstrates that depolarization rate analysis is a potential technique to predict if a VT is epicardial in nature.

The Influence of Epicardial Resistance on Microvascular Resistance Reserve.

BACKGROUND: The optimal index of microvascular function should be specific for the microvascular compartment. Yet, coronary flow reserve (CFR), despite being widely used to diagnose coronary microvascular dysfunction (CMD), is influenced by both epicardial and microvascular resistance. Conversely, microvascular resistance reserve (MRR) adjusts for fractional flow reserve (FFR), and thus is theoretically independent of epicardial resistance. OBJECTIVES: The authors tested the hypothesis that MRR, unlike CFR, is not influenced by increasing epicardial resistance, and thus is a more specific index of microvascular function. METHODS: In a cohort of 16 patients who had undergone proximal left anterior descending artery stenting, we created 4 grades of artificial stenosis (no stenosis, mild, moderate, and severe) using a coronary angioplasty balloon inflated to different degrees within the stent. For each stenosis grade, we calculated CFR and MRR using continuous thermodilution (64 measurements of each) to assess their response to changing epicardial resistance. RESULTS: Graded balloon inflation resulted in a significant sequential decrease in mean FFR (no stenosis: 0.82 ± 0.05; mild: 0.72 ± 0.04; moderate: 0.61 ± 0.05; severe: 0.48 ± 0.09; P < 0.001). This translated into a linear decrease in mean hyperemic coronary flow (no stenosis: 170.5 ± 66.8 mL/min; mild: 149.8 ± 58.8 mL/min; moderate: 124.4 ± 53.0 mL/min; severe: 94.0 ± 45.2 mL/min; P < 0.001). CFR exhibited a marked linear decrease with increasing stenosis (no stenosis: 2.5 ± 0.9; mild: 2.2 ± 0.8; moderate: 1.8 ± 0.7; severe: 1.4 ± 0.6), corresponding to a decrease of 0.3 for a decrease in FFR of 0.1 (P < 0.001). In contrast, MRR exhibited a negligible decrease across all stenosis grades (no stenosis: 3.0 ± 1.0; mild: 3.0 ± 1.0; moderate: 2.9 ± 1.0; severe: 2.8 ± 1.0), corresponding to a decrease of just 0.05 for a decrease in FFR of 0.1 (P < 0.001). CONCLUSIONS: MRR, unlike CFR, is minimally influenced by epicardial resistance, and thus should be considered the more specific index of microvascular function. This suggests that MRR can also reliably evaluate microvascular function in patients with significant epicardial disease.

Catheter Ablation of Idiopathic Epicardial Outflow Tract Premature Ventricular Contractions: A Case Report and Review of the Literature.

The epicardial outflow tract can be a site of origin of idiopathic ventricular arrhythmias. These arrhythmias are most commonly perivalvular and can be targeted from within the coronary venous system or from other adjacent structures, such as the right ventricular and left ventricular outflow tracts or the coronary cusp region. The authors report a case of an epicardial idiopathic outflow tract premature ventricular contraction originating from the midseptal epicardial left ventricle. In this case, direct epicardial access was crucial to identify early local activation and achieve successful catheter ablation.

Restoration of Epicardial Blood Flow After Left Ventricular Unloading With the Impella CP Heart Pump in a Patient With STEMI Treated With Surgical Revascularization.

Left main occlusion presenting as ST-segment elevation myocardial infarction is an exceedingly morbid condition. This article reports a case of cardiac arrest in a patient after a treadmill stress test. Coronary angiography revealed 100% occlusion of the left main coronary artery. Left ventricular unloading with the Impella CP heart pump (ABIOMED/Johnson & Johnson MedTech) was used, after which epicardial blood flow was restored without angioplasty. The patient underwent surgical revascularization. Despite a prolonged revascularization time, there was no evidence of severe myocardial injury postoperatively.

Detection of Epicardial Connection Through Intercaval Bundle Involving Right Pulmonary Veins After Ipsilateral Circumferential Ablation by Intra-Atrial Activation Sequence Pacing From the Right Pulmonary Vein.

BACKGROUND: An epicardial connection (EC) through the intercaval bundle (EC-ICB) between the right pulmonary vein (RPV) and right atrium (RA) is one of the reasons for the need for carina ablation for PV isolation and may reduce the acute and chronic success of PV isolation. We evaluated the intra-atrial activation sequence during RPV pacing after failure of ipsilateral RPV isolation and sought to identify specific conduction patterns in the presence of EC-ICB. METHODS AND RESULTS: This study included 223 consecutive patients who underwent initial catheter ablation of atrial fibrillation. If the RPV was not isolated using circumferential ablation or reconnected during the waiting period, an exit map was created during mid-RPV carina pacing. If the earliest site on the exit map was the RA, the patient was classified into the EC-ICB group. The exit map, intra-atrial activation sequence, and RPV-high RA time were evaluated. First-pass isolation of the RPV was not achieved in 36 patients (16.1%), and 22 patients (9.9%) showed reconnection. Twelve and 28 patients were classified into the EC-ICB and non-EC-ICB groups, respectively, after excluding those with multiple ablation lesion sets or incomplete mapping. The intra-atrial activation sequence showed different patterns between the 2 groups. The RPV-high RA time was significantly shorter in the EC-ICB than in the non-EC-ICB group (69.2±15.2 versus 148.6±51.2 ms; P<0.001), and RPV-high RA time<89.0 ms was highly predictive of the existence of an EC-ICB (sensitivity, 91.7%; specificity, 89.3%). CONCLUSIONS: An EC-ICB can be effectively detected by intra-atrial sequencing during RPV pacing, and an RPV-high RA time of <89.0 ms was highly predictive.

Epicardial Adipose Tissue Thickness and Preserved Ejection Fraction Heart Failure.

PURPOSE OF THE REVIEW: Preserved ejection fraction heart failure and obesity frequently coexist. Whether obesity plays a consistent role in the pathogenesis of preserved ejection fraction heart failure is unclear. Accumulation of visceral adiposity underlies the pathogenic aftermaths of obesity. However, visceral adiposity imaging is assessed by computed tomography or magnetic resonance and thus not routinely available. In contrast, epicardial adiposity thickness is assessed by echocardiography and thus routinely available. We review the rationale for assessing epicardial adiposity thickness in patients with preserved ejection fraction heart failure and elevated body mass index. RECENT FINDINGS: Body mass index correlates poorly with visceral, and epicardial adiposity. Visceral and epicardial adiposity enlarges as preserved ejection fraction heart failure progresses. Epicardial adiposity may hasten the progression of coronary artery disease and impairs left ventricular sub-endocardial perfusion and diastolic function. Epicardial adiposity thickness may help monitor the therapeutic response in patients with preserved ejection failure heart failure and elevated body mass index.

The dysfunctional adiposity index is a clinical surrogate of pericardial fat in adults without premature CVD: A sub-analysis of the GEA Mexican study control group.

BACKGROUND AND AIM: The Dysfunctional Adiposity Index (DAI) is a clinical surrogate for evaluating adipose tissue functionality and cardiometabolic health. However, its association with Pericardial Fat Volume (PFV) has not been tested. The aim of this study was to evaluate DAI- PFV association, stratified by type 2 diabetes (T2D) status, and identify DAI thresholds for detecting increased PFV among patients without premature CVD. METHODS AND RESULTS: Participants from the GEA-Mexican study underwent a computed tomography scan to measure PFV. Adjusted logistic regression analyses tested the association between DAI and PFV. AUROC curves evaluated DAI's ability to identify elevated PFV (≥57.57 cm³), and the Youden method determined DAI thresholds, along with diagnostic metrics. The study analyzed 997 participants (women: 55%; mean age: 54 ± 9 years; median PFV: 42 cm³ [IQR: 29-58]), with a 13% prevalence of T2D. DAI was positively associated with elevated PFV (OR: 1.33, 95% CI: 1.07-1.70), which was more pronounced among subjects with T2D (OR: 3.01, 95% CI: 1.41-6.40). DAI thresholds were established for all participants (>1.176), individuals without T2D (>1.003), and with T2D (>1.936), yielding sensitivities of 71%, 81%, and 57%, and specificities of 48%, 38%, and 75%, respectively. The adjusted logistic regression tied DAI thresholds to a 1.68-fold elevation in PFV for all, 2.06-fold for those without T2D, and 6.81-fold for those with T2D. CONCLUSION: DAI was positively associated with increased PFV, particularly among participants with T2D. Established DAI thresholds demonstrated good diagnostic values for detecting increased PFV. DAI could serve as an accessible marker to identify PF in clinical settings.

Impact of epicardial adipose tissue on cardiac function and morphology in patients with diastolic dysfunction.

AIMS: This study aimed to identify the impact of increased epicardial adipose tissue (EAT) and its regional distribution on cardiac function in patients with diastolic dysfunction. METHODS AND RESULTS: Sixty-eight patients with exertional dyspnoea (New York Heart Association ≥II), preserved ejection fraction (≥50%), and diastolic dysfunction (E/e' ≥ 8) underwent rest and stress right heart catheterization, transthoracic echocardiography, and cardiovascular magnetic resonance (CMR). EAT volumes were depicted from CMR short-axis stacks. First, the impact of increased EAT above the median was investigated. Second, the association of ventricular and atrial EAT with myocardial deformation at rest and during exercise stress was analysed in a multivariable regression analysis. Patients with high EAT had higher HFA-PEFF and H2FPEFF scores as well as N-terminal prohormone of brain natriuretic peptide levels (all P < 0.048). They were diagnosed with manifest heart failure with preserved ejection fraction (HFpEF) more frequently (low EAT: 37% vs. high EAT: 64%; P = 0.029) and had signs of adverse remodelling indicated by higher T1 times (P < 0.001). No differences in biventricular volumetry and left ventricular mass (all P > 0.074) were observed. Patients with high EAT had impaired atrial strain at rest and during exercise stress, and impaired ventricular strain during exercise stress. Regionally increased EAT was independently associated with functional impairment of the adjacent chambers. CONCLUSIONS: Patients with diastolic dysfunction and increased EAT show more pronounced signs of diastolic functional failure and adverse structural remodelling. Despite similar morphological characteristics, patients with high EAT show significant cardiac functional impairment, in particular in the atria. Our results indicate that regionally increased EAT directly induces atrial functional failure, which represents a distinct pathophysiological feature in HFpEF.

Epicardial adipose tissue and pericardial constraint in heart failure with preserved ejection fraction.

AIMS: Obesity and epicardial adiposity play a role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF), and both are associated with increased filling pressures and reduced exercise capacity. The haemodynamic basis for these observations remains inaccurately defined. We hypothesize that an abundance of epicardial adipose tissue (EAT) within the pericardial sac is associated with haemodynamic signs of pericardial constraint. METHODS AND RESULTS: HFpEF patients who underwent invasive heart catheterization with simultaneous echocardiography were included. Right atrial pressure (RAP), right ventricular end-diastolic pressure, and pulmonary capillary wedge pressure (PCWP) were invasively measured. The presence of a square root sign on the right ventricular pressure waveform and the RAP/PCWP ratio (surrogate parameters for pericardial constraint) were investigated. EAT thickness alongside the right ventricle was measured on echocardiography. Sixty-four patients were studied, with a mean age of 73 ± 10 years, 64% women, and a mean body mass index (BMI) of 28.6 ± 5.4 kg/m2. In total, 47 patients (73%) had a square root sign. The presence of a square root sign was associated with higher BMI (29.3 vs. 26.7 kg/m2, P = 0.02), higher EAT (4.0 vs. 3.4 mm, P = 0.03), and higher RAP (9 vs. 6 mmHg, P = 0.04). Women had more EAT than men (4.1 vs. 3.5 mm, P = 0.04), despite a comparable BMI. Women with a square root sign had significantly higher EAT (4.3 vs. 3.3 mm, P = 0.02), a higher mean RAP (9 vs. 5 mmHg, P = 0.02), and a higher RAP/PCWP ratio (0.52 vs. 0.26, P = 0.002). In men, such associations were not seen, although there was no significant interaction between men and women (P > 0.05 for all analyses). CONCLUSIONS: Obesity and epicardial adiposity are associated with haemodynamic signs of pericardial constraint in patients with HFpEF. The pathophysiological and therapeutic implications of this finding need further study.

Inflammatory biomarkers, angiogenesis and lymphangiogenesis in epicardial adipose tissue correlate with coronary artery disease.

In this study, we explored the relationship between inflammatory adipokine levels and coronary artery disease (CAD). We collected subcutaneous adipose tissues(SAT), pericardial adipose tissues(PAT), and epicardial adipose tissues (EAT) and serum samples from 26 inpatients with CAD undergone coronary artery bypass grafting and 20 control inpatients without CAD. Serum inflammatory adipokines were measured by ELISA. Quantitative real-time PCR and western blot were used to measure gene and protein expression. Adipocyte morphology was assessed by H&E staining. Immunohistochemistry and immunofluorescence were used to measure endothelial and inflammatory markers. Serum pro- and anti-inflammatory adipokine levels were higher and lower, respectively, in the CAD group than those in the control group (P < 0.05). In CAD, the pro-inflammatory adipokine levels via ELISA in EAT and PAT were elevated. Pro-inflammatory adipokine mRNA expression was increased, while anti-inflammatory adipokine mRNA expression decreased, in CAD relative to NCAD in EAT and PAT rather than SAT. In EAT, adipocyte area and macrophage-specific staining were lower, while lymphatic vessel marker expression was higher in CAD. Additionally, the endothelial marker expression in EAT was higher than PAT in CAD. The three tissue types had different blood vessel amounts in CAD. The regulation and imbalance expression of the novel biomarkers, including inflammatory adipokine, macrophage infiltration, angiogenesis, and lymphangiogenesis in EAT and PAT, may be related to the pathogenesis of CAD. The serum levels of inflammatory adipokines may correlate to CAD, which requires large sample size studies to get further validation before clinic practice.

COVID-19 Vaccine-Related Myocardial and Pericardial Inflammation.

PURPOSE OF REVIEW: To review myocarditis and pericarditis developing after COVID-19 vaccinations and identify the management strategies. RECENT FINDINGS: COVID-19 mRNA vaccines are safe and effective. Systemic side effects of the vaccines are usually mild and transient. The incidence of acute myocarditis/pericarditis following COVID-19 vaccination is extremely low and ranges 2-20 per 100,000. The absolute number of myocarditis events is 1-10 per million after COVID-19 vaccination as compared to 40 per million after a COVID-19 infection. Higher rates are reported for pericarditis and myocarditis in COVID-19 infection as compared to COVID-19 vaccines. COVID-19 vaccine-related inflammatory heart conditions are transient and self-limiting in most cases. Patients present with chest pain, shortness of breath, and fever. Most patients have elevated cardiac enzymes and diffuse ST-segment elevation on electrocardiogram. Presence of myocardial edema on T2 mapping and evidence of late gadolinium enhancement on cardiac magnetic resonance imaging are also helpful additional findings. Patients were treated with non-steroidal anti-inflammatory drugs and colchicine with corticosteroids reserved for refractory cases. At least 3-6 months of exercise abstinence is recommended in athletes diagnosed with vaccine-related myocarditis. COVID-19 vaccination is recommended in all age groups for the overall benefits of preventing hospitalizations and severe COVID-19 infection sequela.