Sinus Of Valsalva Research Articles

Feasibility and Safety of Pulsed Field Ablation at the Ventricular Outflow Tract Using Focal Point Catheter

BackgroundVentricular arrhythmias commonly originate from the ventricular outflow tract (VOT). It remains unexplored whether pulsed-field ablation (PFA) can create durable lesions safely at the VOT. ObjectiveThis study aimed at evaluating the feasibility and safety of a novel PFA catheter to deliver focal ablation to the VOT, especially pulmonary and aortic sinus cusps (PSCs and ASCs). MethodsTwelve swine were divided into three groups: 24-hour, 2-week, and 4-week post-ablation. PFA was delivered to pre-defined sites of PSCs and ASCs with a focal point catheter, positioned via mapping system, fluoroscopy, and intracardiac echocardiography (ICE). Electrophysiologic assessment, coronary angiography, transesophageal echocardiogram (TEE), gross and histologic examination were performed to evaluate the impact of PFA delivery on cardiac structure and function. ResultsAll subjects survived, and no adverse events were observed. There was a significant decrease in voltage amplitude and increase in pacing thresholds at PSCs and ASCs. There were no significant differences in A-H or H-V intervals between pre- and post-ablation (A-H, P = .70; H-V, P = .90). After PFA delivery to ASCs, coronary arteries were fully perfused in each heart, without ST-segment elevation observed. No severe valvular dysfunction was observed based on ICE and TEE. Gross and histologic examination confirmed the creation of well-demarcated lesions at the targeted sites without damage to adjacent structures. ConclusionPFA delivered via the focal point catheter could create durable lesions at PSCs and ASCs without damage to coronary arteries, atrioventricular block, or valvular dysfunction, indicative of the feasibility and safety of this novel PFA catheter at the VOT.

Association of lifelong exercise characteristics with aortic pathology in patients with Marfan syndrome

Abstract Background Marfan syndrome (MFS) is a genetic connective tissue disease with an increased risk for aortic root dilatation and aortic dissection. Current guidelines, based on expert consensus, recommend exercise restrictions due to concerns that exercise-induced hemodynamic stress may accelerate aortopathy. Studies examining exercise characteristics and their association with aortopathy in MFS patients are lacking. Purpose To assess the association of lifelong exercise characteristics (volume, intensity and type) with the presence of aortic dilatation in MFS patients. Methods An international multi-centre study was conducted in MFS adults. Patients were classified as sedentary (<500 metabolic equivalent of task minutes per week [MET-min/wk]), active (500-1000 MET-min/wk), or highly active (≥1000 MET-min/wk) based on lifelong exercise volumes assessed by a validated questionnaire. Patient’s dominant exercise intensity was classified as moderate (3-6 MET) or vigorous (≥6 MET), and sport type as skill, power, mixed, or endurance. Echocardiography was used to assess diameters at the sinuses of Valsalva (SoV) and ascending aorta (AA), and Campens Z-scores were calculated. Aortic dilatation was evaluated as a diameter ≥40, ≥45 mm, a Z-score ≥2 or ≥3 respectively. Results 315 patients (36[27-49] years, 53% male) were included of which 104 were sedentary, 77 active and 134 highly active (Fig. 1). 42 patients did not perform sport-related exercise, whereas 147 and 121 patients predominantly participated in moderate or vigorous intensity sports. Patients performing sports were allocated to the skill (n=13), power (n=27), mixed (n=158), endurance (n=66) or non-dominant (n=9) exercise type group. Mean SoV and AA diameters were 42.9±7.7 mm and 33.9±7.3 mm. SoV or AA diameters of ≥40 mm were present in 200 (64%) and 41 (13%) patients, whereas 223 (71%) and 81 (26%) patients had a Z-score ≥2 for the SoV or AA. Exercise volume was not associated with SoV dilatation (Fig. 2). Moderate and vigorous intensity sports were associated with a lower prevalence of SoV Z-score ≥3. Power sport was associated with a lower prevalence of all definitions of SoV dilatation, whereas mixed and endurance sports were associated with a lower prevalence of SoV Z-score ≥3. No associations were found with AA dilatation. Of the 17 (5%) patients who suffered from an aortic dissection, 1 case occurred during walking (type A dissection) whereas all other cases were not exercise-related. Conclusions Lifelong exercise volumes were not associated with aortic dilatation in MFS patients. Power sports and vigorous intensity exercise were inversely related to SoV dilatation. Further investigation is warranted to clarify whether this association reflects that patients engaging in these activities have a less severe cardiovascular phenotype, or that they are protected from exercise-related aortic complications, and if patients may miss health benefits due to too exercise restrictions.

Aortic valve tract dynamics in normal-flow low-gradient and normal-flow high-gradient severe aortic stenosis

Abstract Introduction Aortic stenosis (AS) is the most common valvular heart disease in developed countries. Severe AS is defined as a mean pressure gradient (MG) ≥ 40 mmHg, a maximum aortic jet velocity≥4 m/s and an aortic valve area (AVA)≤1 cm2. However, classification of AS severity may be challenging due to discordant results on echocardiography. The normal-flow low-gradient severe AS (NFLG-AS) is defined as AVA≤1 cm2, MG<40 mmHg, left ventricular ejection fraction ≥ 50%, and stroke volume index (SVi) ≥ 35 ml/m2, whereas in the presence of MG > 40mmHg the condition is described as normal-flow high-gradient AS (NFHG-AS). Purpose The purpose of this study was to seek differences in the dynamic changes of the aortic valve tract throughout the cardiac cycle between the two clinical entities: NFHG-AS (Group 1) and NFLG-AS (Group 2). Methods In total, 130 patients with normal flow severe AS who underwent TAVI and had 3D transoesophageal echocardiographic data sets were screened. 38 patients with NFHG-severe AS and 40 patients with NFLG-severe AS with matching clinical characteristics and aortic valve area were identified. A custom-made semi-automated application developed by SQ was used. The application allows tracking of the aortic valve tract surface throughout the cardiac cycle in 3D transoesophageal echocardiograms and provides measurements of the geometrical planes at 4 levels: left ventricular outflow tract (LVOT), aortic annulus (AoA), sinuses of Valsalva (SoV) and sinotubular junction (STJ). Results The echocardiographic characteristics and the dynamic changes of the aortic valve tract between the two groups are shown in Tables 1 and 2. Both groups had comparable echocardiographic characteristic apart from the mean aortic valve pressure gradient as expected. With regards to the aortic valve tract geometrical dynamic changes, the relative LVOT and AoA area changes were bigger in Group 1 (36.8±15.9% vs 29.1±11.9%; p=0.017 and 21.0±8.39% vs 17.1±6.6%; p=0.028). The SoV and STJ relative changes were similar between the two groups. The same applies to aortic stiffness parameters, namely compliance and distensibility of the ascending aorta, systemic arterial compliance, and valvulo-arterial impedance. Conclusion The LVOT and aortic annulus area demonstrate more prominent dynamic changes in patients with normal-flow high-gradient severe AS compared to individuals with normal-flow low-gradient severe AS. While the SoV and the STJ geometry does not change significantly through the cardiac cycle, a more elastic outflow tract allows larger expansion in systole and higher pressure gradients across the aortic valve, whereas a stiffer outflow tract and annulus result in lower pressure gradients, despite the presence of severe aortic stenosis (AVA<1.0cm2). These differences in dynamic LVOT and aortic annulus changes may explain the discrepancy between aortic valve area and pressure gradients in patients with normal-flow low-gradient AS.

Distal ascending aortic dilatation portends a near 2-fold greater risk of cardiovascular mortality than proximal enlargement: results from 120,000 patients in a nationwide echocardiographic database

Abstract Background The management of thoracic aortic dilatation is clinically challenging and acute aortic dissection (AD) is under-recognised as a primary cause of death. Despite the majority of AD occurring in non-severely dilated aortas, absolute aortic diameter remains the most utilised criterion for adjudging preventative surgical correction. In order to improve outcomes and guide management, greater prognostic understanding is needed. Purpose We examined a nationwide echocardiographic dataset linked to mortality outcomes to determine how ascending thoracic aortic dilatation and its site affects cardiovascular disease (CVD) mortality over time. Methods The National Echocardiography Database Australia (NEDA) was examined for aortic dimensions at the sinuses of Valsalva (SoV), sinotubular junction (STJ) and ascending aorta (AscAo) in patients who had undertaken >1 echocardiographic study. Following separation of those who had undergone corrective aortic surgery, patients were stratified according to absolute aortic diameters and grouped as normal (<4cm), mild (4.0-4.5cm), moderate (4.5-5cm) and severely (>5cm) dilated at the prescribed thoracic aortic sites. Mortality data was then linked from the National Death Index (NDI). Results 398,905 echocardiographs from 121,115 patients with a mean age of 62.6±16.2 years were included. At the time of mortality data linkage, 38,681 (32%) had died, of whom 13,292 (34%) died from CVD causes and only 276 (0.007%) had aortic dissection recorded as their primary cause of death. Severe aortic dilatation at any site increased the likelihood of 10-year CVD mortality (29% vs. 15% in those with normal diameters; HR 3.00; CI 1.60-5.63; p<0.0001), with an incremental increase in the probability of CVD death when moving from the proximal to distal ascending aorta; 10-year CVD mortality at the SoV 26% (HR 1.93; CI 1.29-2.87; p<0.001), STJ 39% (HR 2.82; CI 1.64-4.86; p<0.001) and AscAo 44% (HR 4.74; CI 2.46-9.13; p<0.001) respectively (Figure 1). When examining those patients who had undergone corrective aortic surgery, the likelihood of 10-year CVD mortality was comparable to the population with normal aortic diameters (17 vs. 15%, HR 1.1; CI 0.9-1.36; p=0.3) (Figure 2). Conclusion Severe aortic dilatation increases the probability of 10-year cardiovascular mortality. Interestingly, there is an incremental increase in the likelihood of CVD mortality when moving from the proximal to distal ascending aorta, with severe AscAo dilatation conferring a near 2-fold greater risk of CVD mortality compared with severe SoV aneurysms. Additionally, surgical aortic intervention nearly normalises survival probability to the population with healthy aortic diameters. These results identify new considerations for prognostication, risk stratification and surgical guidance of aortic repair.CVD mortality by aortic dilatationCVD mortality after aortic intervention

Marfan syndrome in children: large, single centre experience on management and outcome

Abstract Introduction Beta-blockers (BBs) and angiotensin receptor blockers (ARBs) have been proved to decrease the growth rate of the aortic root in Marfan patients, we describe our single centre experience at a large tertiary paediatric institution. Methods This is a retrospective longitudinal study of a large, paediatric only, Marfan cohort through review of medical notes for clinical data and treatment and assessment of serial echocardiograms. Results 167 patients were included, mean age at first assessment was 4.05 ± 3.12 years, 86 (51.50%) were males. 41 pts (24.55%) had a de novo FBN1 mutation. A 35.32% had a cysteine loss mutation. Median follow up was 9.54±4.37 years. 2 patients had a clinical and molecular diagnosis of early-onset Marfan, they both underwent mitral valve surgery in infancy and one of them died at 7 years old. No other deaths or acute aortic events in our cohort until transition to adult services at 18 years old. Of the entire study population 12 pts (7.2%) underwent aortic surgery at a median age of 13±7.02 years, 1 patient had a mitral valve repair. Chemoprophylaxis (currently only evaluated in a subgroup of our youngest 65 patients) was offered to all patients, 27.69% declined medicines. The remining 47 subjects are on treatment which was started at a mean age of 4.88 ±2.96 years, surveillance data available for a mean follow up of 2.75±2.41 years. 50 received BB (58.50% atenolol [average dose 0.79 mg/kg/day] and 19.15% bisoprolol [average dose 0.087 mg/kg/day]), 5 (8.51%) losartan [average dose 0.763 mg/kg/day], and 10 (15.38%) double therapy with BB and ARBs. The Sinus of Valsalva (SOV) z-scores, as assessed on echocardiograms and normalised according to Lopez dataset, showed a reduction over time in children treated with chemoprophylaxis (see figure 1). SOV mean z-score at starting treatment was 3.38 ± 2.06 which reduced to 2.79± 1.81, however, differences were not statistically significant (paired T-student p-value 0.078). In non-treated patients, initial SOV z-score was 1.89 ± 1.05. When comparing evolution there was a trend towards decreased average SOV z-score over the years in the treated group, not seen in the non-treated patients (see figure 2). No statistical differences in the SOV z-score reduction change were found when comparing different treatment groups (ANOVA p-value 0.851), but a tendency to more profound decrease in the losartan groups was observed. Reduction in blood pressure or heart rate did not differ amongst the treatment groups. Conclusions We present one of the largest single centre reviews on management of paediatric Marfan patients. Our data confirm a decrease in SOV z-score with chemoprophylaxis in a real-world cohort. This is in line with current evidence and corroborates clinical practice.SOV Z-SCORE EVOLUTION AFTER TREATMENTSOV Z-SCORE GROUP AVERAGE CHANGE

Biomimetic porphyrin-lipid nanoparticles - novel nanoscale theranostics for multimodal imaging and therapy in atherosclerotic cardiovascular disease

Abstract Background High-density lipoprotein (HDL) mimetic nanoagents have unrealized potential for atherosclerosis theranostics. Porphyrin-lipid HDL mimetic nanoparticles (Por-HDL-NPs) incorporate a porphyrin-lipid conjugate which permits near infrared fluorescence imaging and positron emission tomography (PET) through chelation of Copper-64 (64Cu). The outer shell contains apolipoprotein A-I mimetic peptide R4F designed to interact with scavenger receptor class B type I (SR-BI), enabling macrophage-targeting and therapeutic effects. Purpose To investigate the multimodal imaging, macrophage-targeting and therapeutic properties of Por-HDL-NPs and applications in atherosclerotic cardiovascular disease. Methods In vitro, the cholesterol efflux capacity of PBS (control), reconstituted HDL (rHDL) and Por-HDL-NPs was determined in immortalized bone marrow-derived macrophages (iBMDMs) loaded with [³H]-cholesterol. Real-time quantitative PCR (RT-qPCR) assessed mRNA levels of inflammatory mediators. ELISAs and Western blotting measured changes in protein levels. Apolipoprotein (Apo)e-/- mice were fed high-cholesterol diet (HCD) for 6 weeks, for early-stage plaque, and 13 weeks for the unstable plaque model in which two partial stenoses were made in the right carotid artery. PET and fluorescence (IVIS, flow cytometry, microscopy) imaging identified Por-HDL-NPs in plaques, circulating and aortic cells. Histological techniques assessed plaque area and composition in aortic sinus and carotid artery sections. Results Por-HDL-NPs were internalized by iBMDMs, visualized via fluorescence microscopy and flow cytometry. Por-HDL-NPs increased cholesterol efflux (49%, P<0.05), compared to rHDL. Por-HDL-NPs reduced macrophage mRNA levels of Il-1b (88%), Il-18 (54%) and Ccl5 (75%), and protein secretion of IL-1β (69%) and CCL5 (82%), P<0.05. Por-HDL-NPs suppressed inflammasome components Nlrp3 (69%) and Asc (36%), and activation of inflammatory transcription factor p65-NF-κB (53%), P<0.05. SR-BI siRNA knockdown and methyl-β-cyclodextrin, revealed that the anti-inflammatory properties of Por-HDL-NPs were independent of SR-BI and cholesterol efflux. In Apoe-/- mice, PET imaging showed 64Cu-Por-HDL-NPs localized in hearts and could detect increases in plaque size over time with HCD feeding. Por-HDL-NP fluorescence was detected within aortic sinus and unstable carotid plaques, co-localized with CD68+ macrophages. Por-HDL-NP-treated mice had smaller early-stage (22%) and unstable plaques (52%) than control PBS-treated mice, P<0.05. Por-HDL-NP mice had fewer circulating (32%) and aortic monocytes (81%), and a reduction in aortic arch Rela (26%), P<0.05. Conclusions Por-HDL-NPs present as potential nanoscale theranostics for atherosclerotic cardiovascular disease. Por-HDL-NPs can detect plaques using multiple imaging modalities and exhibit atheroprotective effects.Atherosclerosis imaging with Por-HDL-NPs

Deletion of the asialyloglycoprotein receptor-1 (ASGR1) causes atheroprotective effects in vitro and in vivo

Abstract Introduction The asialoglycoprotein receptor 1 (ASGR1) is a hepatic receptor that clears desialylated glycoproteins from the circulation. A loss-of-function mutation in ASGR1 was reported to associate with a 34% reduction in coronary artery disease (CAD) risk, suggesting a role for ASGR1 in CAD. Aim To determine the role of ASGR1 in atherosclerosis and whether deletion of ASGR1 elicits atheroprotective effects. Methods Western blotting, mass spectrometry and flow cytometry assessed ASGR1 expression in cultured macrophages or immune cells collected from the blood and aortas of wildtype mice. Bone marrow-derived macrophages (BMDMs) from wildtype and Asgr1-/- mice were subjected to cholesterol efflux and oxidised low-density lipoprotein (oxLDL) uptake in vitro functionalassays. ELISA and qPCR measured changes in lipid regulators in BMDMs. Asgr1-/- mice were crossed with atherosclerosis-prone apolipoprotein (Apo)e-/- mice (Apoe-/-Asgr1-/-). Stable plaque area was assessed histologically in the aortic sinuses of mice fed a high-cholesterol diet for 8 weeks (n=16/group). Using the tandem stenosis surgical model, unstable plaque was assessed in carotid arteries (n=10/group). Human ASGR1 was measured by ELISA in peripheral blood mononuclear cells (PBMCs) isolated from patient samples (n=18). Results Western blotting and mass spectrometry discovered ASGR1 is expressed in macrophages. Immunofluorescence identified the presence of ASGR1 in aortic sinus plaque. Flow cytometry revealed ASGR1 is expressed in both inflammatory and patrolling monocytes, neutrophils, macrophages and dendritic cells of blood and aortas. Asgr1-/- BMDMs elicited greater cholesterol efflux (+39%, P<0.05) and decreased oxLDL uptake (-15%, P<0.05), compared to wildtype BMDMs. Moreover, Asgr1-/- BMDMs had significantly higher LDL receptor protein levels (+2-fold), and Lxra (+2-fold) and Pparg (+1.5-fold) mRNA levels than wildtype BMDMs, P<0.001. Plasma from Asgr1-/- mice had lower total (-25%, P<0.05) and LDL (-36%, P<0.05) cholesterol concentrations than wildtype mice. Apoe-/-Asgr1-/- mice developed less stable plaque in aortic sinuses (-37%, P<0.001) than Apoe-/- controls, as well as smaller unstable plaques in carotid arteries (-49%, P<0.05). Finally, in a human population, ASGR1 protein levels were higher in PBMCs from patients with coronary plaque (+61%, P<0.05), than those without plaque, determined from coronary angiograms. Conclusion ASGR1 is expressed on monocytes, macrophages and in plaques, and human PBMC ASGR1 associates with coronary plaque. Deletion of ASGR1 causes atheroprotective functions in macrophages in vitro and reduced plaque burden in vivo. Our findings demonstrate ASGR1 is important in atherosclerosis with implications for ASGR1 as a therapeutic target.

Cardiovascular health in women with turner's syndrome: a 3-year single centre audit

Abstract Background Turner’s syndrome (TS) is the most common genetic abnormality affecting females and is characterised by complete or partial absence of the X chromosome. Mortality is predominantly related to cardiovascular disease (1). Risk of life-threatening aortic dissection is 40 per 100,000 (2). Indexed aorta size (ASI) to body surface area (BSA) >20mm/m² is considered abnormal. An ASI of ≥25mm/m² is associated with increased risk of aortic dissection (3). Despite this there is a paucity of data in the literature regarding TS cardiovascular disease and providing evidence-based care can be challenging. Purpose Define cardiovascular disease, with focus upon aortopathy in our TS Cardiovascular Clinic (TCC). Methods Single centre retrospective medical record analysis of 248 women with TS (2021-2024) Results Patient baseline characteristics; mean age 37 years (range 18-75yrs), height 150cm (132-169cm), weight 62kg (37-130kg), BSA 1.55m² (1.19-2.17m²). 65 patients (29%) had bicuspid aortic valve (BAV), 19 (8%) and 5 (3%) had repaired and un-repaired aortic coarctation (CoA) respectively. 30 (13%) had other congenital heart disease, with most common was partial anomalous pulmonary venous connection (12 patients: 5%). 22/248 patients had previous aortic root surgery; 20 elective (mean ASI 29mm/m², range 26-33mm/m², mean age at time of surgery 42 years); 2 presented with aortic dissection (ASI 21mm/m²; pregnant, BAV & 24mm/m²; tri-leaflet aortic valve, TAV). Data was available for 221 unoperated patients (figure 1). The site of maximal dimension was observed at the sinus of Valsalva in 70% compared to 30% at the ascending aorta. 130 patients (59%) had maximal ASI of <20mm/m². Dimensions of 20-23mm/m² and 23-25mm/m² were seen in 64 (29%) and 18 (8%) patients respectively. 7 patients (3%) had a maximal ASI of >25mm/m². 4 patients (2%) had an absolute maximal dimension of 40mm with ASI of 23mm/m² for all four. 9/11 patients with dimension ≥25mm/m² or 40mm had a body mass index (BMI) >25kg/m². Review of medical history for patients at and above threshold for risk of aortic dissection revealed referral to or previous discussion in an Aortic multi-disciplinary meeting (MDT) with a plan for ongoing surveillance. 57 patients (35%) with TAV had significant aortopathy (mean age 46years, range 19-75years) compared with 33 (51%) with BAV (mean age 39yrs, range 22-72 years) (figure 2). Review of patients >55years of age demonstrated a very similar burden of aortopathy in both TAV (14%) and BAV (15%) populations. Conclusions A high burden of cardiovascular disease exists within our TS population. There is a very high prevalence of aortopathy, increasingly with age and both with and without the presence of a bicuspid aortic valve. More published data is needed to help better define those at risk.

2D Echocardiographic aortic root dimensions and longitudinal analysis with artificial intelligence using an open dataset from a UK-wide collaborative

Abstract Background Surveillance of aortic dimensions requires reproducible measurements, and knowledge of the rate of progression in those with dilatation. Purpose To develop an open machine-learning method for measuring the aortic root and proximal ascending aorta on echocardiograms, validate it through a multi-expert panel from the Unity UK Echocardiography AI Collaborative, and applying the AI to derive the rate of progression in historical databases. Methods The neural network was trained on 1478 parasternal long-axis images. Each image was labelled with key points for the aortic annulus, sinus and sinotubular junction, and proximal ascending aorta dimensions. Labels accommodated inner-to-inner and leading-to-leading conventions. For validation, the end-diastolic and mid-systolic images were identified (accommodating different guidelines recommendations) from 100 studies, and 10 expert echocardiographers made the aortic measurements. The consensus of experts defined the reference standard, and the variation between individual experts defined the acceptable variation for the AI. The AI was then applied to 724 echocardiograms of 102 patients under surveillance spanning 12 years (ranging from 4 to 17 scans per patient) without intervention. Training data labels and networks are made freely available on our project website. Results The median absolute deviations between the AI and the expert consensus ranged from 0.06cm to 0.17cm across the 16 measurements. For the individual expert opinions this was from 0.08cm to 0.19cm. For 7/16 measurements, there was no statistically significant difference between the AI deviation and the individual-expert deviation. The AI’s confidence level was a useful indicator of the reliability of the AI measure. For the top 9 deciles of AI confidence level, the AI measurements had significantly smaller deviations than the individual experts. The rates of progression averaged across the three aortic measurements was 2.0 mm/decade (95% CI 1.0 to 3.0; p =0.007). Conclusion Expert consensus can be used to both define the reference standard and also the range of acceptable deviation from consensus. Overall, the AI performs similarly to experts and more importantly, provides an automated estimate of confidence. The validated AI is consistent over time, and when applied retrospectively to patients with dilated aortic roots, found the rate of progression was more rapid than in previously reported healthy patients. This approach could be applied generally in developing medical AI to not only make reproducible measurements but to automate large scale longitudinal studies with little input, and ultimately serves as a useful research and clinical tool.Figure: AI(red) vs Expert (blue)Table: AIDeviations from Consensus

Safety and efficacy of ultra-long intermediate-power ablation for outflow tract ventricular arrhythmia arising from the left ventricular summit

Abstract Background Radiofrequency ablation (RFA) has been effective in managing premature ventricular contractions (PVCs). Despite improvement in ablation techniques, recurrence remains high for LV summit PVCs. Epicardial ablation here is often precluded due to fat and proximity to coronaries, thus, aggressive but safe endocardial options are needed. Purpose To evaluate the safety and effectiveness of ultra-long ablation (>240 seconds) duration for refractory LV summit PVCs. Methods Patients with deep intramural LV summit PVCs were identified by lack of PVC elimination or late (>60 s suppression) and recurrence post-lesion under the left aortic sinus of Valsalva. We included patients who received the longest RFA of at least 240 seconds (maximum 15 minutes). RFA power was titrated slowly from 20 to 35W, carefully ensuring that the impedance drop did not exceed 12 ohms. Acute procedure success was defined as clinical PVC suppression for ≥60 minutes after the last lesion. Short-term success was defined as symptom improvement, ejection fraction (EF) recovery, and drop in PVC burden at 3 months. Results Twenty patients (59.5 ± 16.4 years, 55% male) were included. Baseline features are shown in Table 1. All RFA were delivered endocardially. No steam pops were noted. PVC burden was significantly lower at 3-month follow-up (P< 0.01), Figure 1A. Most patients had a normal ejection fraction (EF) at baseline; thus, no significant difference change in EF was observed (Figure 1B). One complication was recorded, which was tamponade likely caused by coronary sinus dissection requiring pericardiocentesis. Acute success was achieved in 95.0% of the cases, and all cases followed at 3 months (18/18) achieved short-term success. Conclusion Ultra-long duration RFA with lesions ≥ 240 seconds at 35W per lesion for LV summit PVCs appeared to be safe and effective in achieving acute and short-term success. The lack of acute suppression should not discourage operators, as there seems to be delayed suppression in some cases. Careful monitoring of biophysics is paramount when attempting this technique.

Gene-echocardiography: unmasking the covert role of fatty acid metabolism gene mutations in adult cardiomyopathy

Abstract Background Although the role of fatty acid metabolic deficiencies in cardiomyopathy is established, the precise identity of causative genes and their respective phenotypes in adult cardiomyopathy remains unclear. Methods We implemented a combination of echocardiography and whole exome sequencing in clinically diagnosed cardiomyopathy patients to uncover this relationship. This involved recording cardiac phenotypes, identifying genes associated with disrupted fatty acid metabolism, and subsequently followed up with these patients. Results Out of 802 cardiomyopathy patients, 27 exhibited mutations in genes tied to fatty acid metabolism. Specifically, 16 patients demonstrated a hypertrophic cardiomyopathy (HCM) phenotype, and 11 showed a dilated cardiomyopathy (DCM) phenotype. The implicated genes were SLC22A5 (n=7), ACADVL (n=6), ACADS (n=4), ACADM (n=3), SLC25A20 (n=3), ACADL (n=2), HADH (n=1), and AGK (n=1), with a higher prevalence in males. Among these, the SLC22A5 mutation was predominant and correlated with HCM phenotype. Notably, compound mutations were frequently observed (16/27), leading to earlier disease onset and diminished aortic sinus dimension. Further investigation showed that smaller aortic sinus dimensions resulted from abnormal left ventricular myocardial work. HCM phenotype mutation carriers showed more consistent left ventricular hypertrophy and a higher probability of right ventricular hypertrophy, while DCM phenotype mutation carriers exhibited impaired contractile function across all left ventricle segments. After a 24-month follow-up, the DCM phenotype group demonstrated higher cardiovascular risk, including two fatalities. Conclusion Our investigation highlights the significant prevalence of mutations related to abnormal fatty acid metabolism in adult cardiomyopathy patients, underscoring the utility of a gene-echocardiography approach for diagnosis.

Gene-echocardiography: refining genotype-phenotype correlations in cardiomyopathy patients with restrictive phenotype

Abstract Background The restrictive phenotype, the least frequent and genetically complex form of cardiomyopathy, is the focus of this investigation. The aim is to clarify the association between restrictive phenotype and genetic variants in cardiomyopathy patient. Methods We utilized whole-exome sequencing in a cohort of 568 cardiomyopathy patients and performed echocardiographic evaluations to identify restrictive phenotypes. Comprehensive analysis of cardiac characteristics and functionality was also undertaken. Results Among the cohort, 33 patients exhibited a restrictive phenotype. These patients were distributed as follows: 7 within the restrictive cardiomyopathy group (RCM), 20 in the hypertrophic cardiomyopathy group (HRCM), and 6 in the dilated cardiomyopathy group (HDRCM). A notable prevalence of gene mutations, mainly in the MYBPC3 gene, was found in these individuals. We observed that mutation carriers, characterized by smaller aortic sinus dimension, demonstrated an association with the mutation and diminished myocardial work. Furthermore, MYBPC3 mutation carriers showed a thicker ventricular wall and a higher predisposition for septal hypertrophy. Both HRCM and HDRCM groups displayed consistent hypertrophic manifestations, with the latter demonstrating a higher frequency of interventricular septal hypertrophy. The 5-year survival rate was calculated at 54.5%, with gene mutations not significantly affecting longevity. Conclusion Genetic factors profoundly influence the restrictive phenotype of cardiomyopathy. There is a strong link between restrictive phenotype and genetic variants in cardiomyopathy, providing a foundation for more accurate genetic testing and personalized management of patients. The emerging "gene-echocardiography" concept may refine the accuracy and productivity of genetic counseling and testing in cardiomyopathy.

Native Sinus Hemodynamics and Thrombosis in Transcatheter Heart Valve: Effect of Implant Depth and Coronary Flow.

This study aimed to investigate the hemodynamic and anatomic factors associated with sinus thrombosis following transcatheter aortic valve replacement (TAVR), integrating invivo patient data analysis and invitro experiments. Postprocedural, 4-dimensional, multiphase computed tomography data from 211 patients enrolled in the ADAPT-TAVR (Anticoagulation Versus Dual Antiplatelet Therapy for Prevention of Leaflet Thrombosis and Cerebral Embolization After Transcatheter Aortic Valve Replacement) study were analyzed. The prevalence of native sinus thrombosis was examined in relation to valve type, implant depth, and anatomic features. Invitro experiments used particle image velocimetry to observe changes in sinus flow based on the transcatheter heart valves (23-mm SAPIEN3, Edwards Lifesciences; and 29-mm CoreValve, Medtronic) height and coronary artery flow. Native sinus thrombosis was more common in self-expanding valves (39.1% versus 14.9%, P=0.004). In per-cusp analysis of invivo patient data, adjusted transcatheter heart valve implant depth (odds ratio, 1.2 [95% CI, 1.1-1.3]; P<0.001), noncoronary sinus of Valsalva (odds ratio, 4.0 [95% CI, 2.0-7.8]; P<0.001), sinus inflow diameter (odds ratio, 0.8 [95% CI, 0.6-0.9]; P=0.008), and implanted valve size (odds ratio, 0.8 [95% CI, 0.7-1.0]; P=0.025) were significant factors associated with native sinus thrombosis. In the invitro experiments, CoreValve showed noticeable flow stasis compared with SAPIEN3. High-positioned SAPIEN3 was linked to reduced velocity within the native sinus of Valsalva. Coronary artery flow led to higher sinus velocity and improved particle washout, reducing sinus thrombosis risk. This study provides insights into the relationship between transcatheter heart valve deployment and native sinus thrombosis, emphasizing the role of anatomic factors in relation to the risk of sinus thrombosis.

Intercoronary communication: a rare coronary anomaly.

Intercoronary communication also known as coronary arcade or coronary cascade is a rare coronary artery anomaly with an incidence of only 0.002% in patients undergoing angiography. This case emphasizes the importance of recognizing this rare anomaly and highlights its clinical significance. We report a case of intercoronary communication in a 56-year-old female who presented with acute chest pain and ST-segment depression in the lateral leads. High-sensitivity troponin-T was elevated and transthoracic echocardiography revealed normal left ventricular function with no regional wall motion abnormality. Hence, the diagnosis of acute coronary syndrome - non-st-elevation myocardial infarction was considered. Coronary angiography revealed a 95% focal stenosis in the major obtuse marginal artery (OM). The right coronary artery (RCA) angiogram revealed a single abnormal channel communicating the right posterolateral branch (PLV) and the distal left circumflex artery (LCX) with retrograde opacification of the proximal LCX, left main coronary artery (LMCA) and left aortic sinus. After she underwent revascularization with the drug-eluting stent to the OM. CT-coronary angiography confirmed the presence of intercoronary communication (ICC) between the right posterolateral branch and the distal LCX artery. No active intervention was done for the ICC. Over a year of follow-up, our patient remained asymptomatic. Angiographically and anatomically, collaterals and intercoronary communications should be differentiated. Obstructive coronary artery disease leads to the development of collaterals, which are typically less than 1mm in diameter, multiple and tortuous. However, ICC tends to be single and straight, usually seen without obstructive disease with unidirectional or bidirectional flow. Histologically, collaterals consist of endothelium supported by poorly organized collagen, muscle and elastic fibers. Meanwhile, ICCs resemble epicardial vessels in that they have a well-defined muscular layer. This case emphasizes the importance of recognizing this rare coronary anomaly and distinguishing it from collaterals to help in accurate diagnosis. Although they can provide an efficient blood supply to the jeopardized myocardium and can aid as a channel during coronary interventions, they can also cause myocardial ischemia by coronary steal.

ASSOCIATIONS BETWEEN AORTIC DIAMETER AND ANTHROPOMETRIC MEASURES IN MEN: A CT STUDY

Cardiovascular diseases are a leading cause of death globally, with Ukraine experiencing a mortality rate of 64.3% in 2019, predominantly affecting men. Aortic aneurysms, assessed by aorta diameter, are significant among these diseases. While computed tomography (CT) is the gold standard for diagnosing aortic syndromes, there's a lack of comprehensive data on aortic morphometrics in Ukraine, particularly in men. This research aims to bridge this gap by analyzing CT-derived data on the ascending aorta in Ukrainian men. Aim. To enhance diagnostic accuracy and guide treatment strategies, including surgical interventions, by understanding the correlation between aortic morphology, age, and anthropometric variables in this high-risk demographic. Materials and methods. The study used DICOM images from computed tomography angiography of the aorta with contrast enhancement and ECG synchronization. Methods included anthropometric assessments, CT imaging, and statistical analysis. The study involved 62 male subjects without heart or ascending aorta pathology. Data included age, body length, and weight, which were used to calculate BMI and BSA. Diameter measurements of the aorta were taken at specific levels: the aortic ring, aortic sinus, sinotubular junction, maximum diameter of the ascending aorta, mid-section of the ascending aorta, and just before the brachiocephalic trunk departure. Statistical analyses employed the Student's t-test and Pearson's correlation analysis, with a significance level of p&lt;0.05. Results. The study encompassed 62 male subjects without cardiovascular pathology, with an average age of 52.56±13.52 years, average body length of 1.76±0.07 m, average body weight of 84.74±14.14 kg, average BMI of 27.54± 4.74 kg/m², and BSA of 2.03±0.18 m². A moderate positive correlation between age and aortic diameter was observed, ranging from +0.35 for the average diameter of the aorta at the aortic ring level to +0.57 for the maximum diameter of the aorta (p&lt;0.05). However, no significant correlations were found between aortic diameters and body height in men (p&gt;0.05). Notably, a moderate positive correlation was observed between body weight and aortic diameter at the sinotubular junction level (r=+0.61, p&lt;0.001) and the aortic sinus level (r=+0.34, p= 0.027). Furthermore, an increase in aortic diameter at the sinotubular junction level was significantly correlated with an increase in BMI (r=+0.59, p&lt;0.001) and BSA (r=+0.57, p&lt;0.001). Additionally, body surface area demonstrated a significant positive correlation with an aortic diameter at the aortic sinus level, exhibiting a moderate positive correlation (r=+0.35, р=0.023). Men with a BMI of 25 kg/m² or higher (n=45) showed significantly larger aortic diameters at almost all levels (excluding the aortic ring diameter) compared to those with lower BMIs (р&lt;0.05). Conclusions. CT-morphometric indicators of the diameter of the aorta in men normally increase with age. Body weight is directly correlated with the diameter of the aorta at the level of the sinotubular junction and aortic sinuses. In men with excess body weight and obesity, larger values of the diameters of the aorta were established at all studied levels, except for the level of the sinotubular junction.

Therapeutic results of three-dimensional aortic valve anatomic repair for regurgitant bicuspid aortic valve

Objective: To explore the surgical technique and results of three-dimensional aortic valve anatomic repair for bicuspid aortic valve (BAV) with aortic regurgitation (AR). Methods: This is a retrospective case series study. From August 2021 to December 2023, 130 consecutive patients with BAV-AR underwent aortic valve anatomic repair at the Department of Cardiothoracic Surgery, Zhongshan Hospital, Fudan University,and the data were retrospectively analyzed. There were 115 males and 15 females, aged (38.6±11.7) years (range: 15 to 67 years). All patients received modified aortic root reconstruction, to do three-dimensional root remodeling, including the basal ring, sinus of Valsalva and sino-tubular junction simultaneously. Perioperative and follow-up data were collected and analyzed. Comparisons between groups were performed using independent samples t-test, Wilcoxon paired signed-rank test, or χ² test. Results: No patient transferred to valve replacement during the operation. The cardiopulmonary bypass time (M(IQR)) was 109 (34) minutes (range:67 to 247 minutes), and the aortic cross-clamp time was 76 (26) minutes (range: 32 to 158 minutes). Preoperative transesophageal echocardiography showed 123 patients (94.6%) presented with moderate or severe regurgitation. Immediately postoperative transesophageal echocardiography showed no regurgitation in 22 patients (16.9%), trace regurgitation in 81 patients (62.3%) and mild regurgitation in 27 patients (20.8%). Follow up was complete in all patients, with a follow-up of 5.5 (9.4) months (range: 0.1 to 27.6 months). No mortality was observed during follow-up. Echocardiography was obtained in 112 patients at the latest follow-up, including no regurgitation in 4 patients (3.6%), trace regurgitation in 58 patients (51.8%), mild regurgitation in 45 patients (40.2%), moderate regurgitation in 4 patients (3.6%), and severe regurgitation in 1 patient (0.9%). Conclusion: For patients with BAV-AR who have good valve quality and no severe aortic sinus dilation, the recent outcomes of three-dimensional anatomical repair technique, focusing on overall remodeling of the aortic root, are satisfactory.

Myeloid GSK3α Deficiency Reduces Lesional Inflammation and Neovascularization during Atherosclerotic Progression.

The molecular mechanisms by which cardiovascular risk factors promote the development of atherosclerosis are poorly understood. We have recently shown that genetic ablation of myeloid glycogen synthase kinase (GSK)-3α attenuates atherosclerotic lesion development in low-density lipoprotein receptor-deficient (Ldlr-/-) mice. However, the precise contributions of GSK3α/β in atherogenesis are not known. The aim of this study is to investigate the effect of GSK3α and/or β deficiency on lesional inflammation and plaque vascularization. Five-week-old female Ldlr-/- mice were fed a high-fat diet for 10 weeks to establish atherosclerotic lesions. Mice were harvested at 15 weeks of age and atherosclerotic lesions were characterized. The results indicate that, in addition to significantly reducing plaque volume, GSK3α-deficiency decreases inflammation, reduces vasa vasorum density at the aortic sinus, and reduces plasma c-reactive protein (CRP) levels. GSK3β-deficiency is associated with decreased plasma CRP levels but does not affect lesional inflammation or vascularization. These results suggest GSK3α may be an applicable target for the development of novel anti-atherogenic therapies.

Aortic Valve Replacement Surgery Caused by IgG4-Related Aortic Regurgitation

While IgG4-related disease affects different organs, it is uncommon to associate it with the aortic valve. The clinical manifestations and prognosis of an uncommon IgG4-related aortic valve disease were examined by reporting it. After common activity, a 50-year-old man experienced shortness of breath and chest tightness. IgG4+ was expressed at a level of 4.23 g/L. The aortic valve had severe reflux, and the ascending aorta and aortic sinus were dilated, as evidenced by transesophageal echocardiography. Pathological results suggested that the ratio of IgG4+ cells to IgG+ cells was over 40%. Thus, the patient was diagnosed with aortic valve disease caused by IgG4+. Surgical treatment was executed. In clinical practice, IgG4-associated aortic regurgitation is uncommon and has the same clinical manifestations as general aortic valve disease. Nevertheless, there was a significant increase in serum IgG4+ levels. There was an association between the two. The pathology of valves can be proven.

Atrial refractoriness early after transcatheter aortic valve implantation TAVI in patients with severe aortic stenosis and sinus rhythm.

Aortic valve stenosis (AS) is a common valvular heart disease, especially in the elderly, and is associated with a high prevalence of atrial fibrillation. Although the risk of atrial fibrillation is expected to decrease after the intervention, atrial fibrillation develops in many patients undergoing surgical or percutaneous transaortic valve implantation. We aimed to evaluate atrial refractoriness since it may play a key role in the occurrence of atrial fibrillation after transaortic valve implantation. Seventy-nine consecutive patients who underwent TAVI between October 2021 and May 2023 were enrolled in this trial. Sixty-seven patients underwent electrophysiology study before and after TAVI. We evaluated the changes in PA and AH intervals, as well as atrial effective refractory periods. Besides the hemodynamic changes, atrial effective refractory periods increased, and atrial effective refractory period dispersion (39.8±21.6 vs. 31.1±18.0) decreased significantly after TAVI. The change in atrial effective refractory period dispersion after TAVI was correlated only with the changes in left ventricular end-diastolic pressure (r=0.77, P=0.001) and the changes in aortic gradient (r=0.4, P=0.001). The independent variables affecting the changes in atrial effective refractory period dispersion were basal pro-BNP levels, besides the changes in left ventricular end-diastolic pressure and aortic gradient after transaortic valve implantation. Our results show an acute improvement in atrial refractoriness after TAVI, though high atrial fibrillation rates are reported in the literature. The timing of aortic valve replacement is important, as irreversible maladaptive changes might have already developed by the time of intervention.

Whole body insulin resistance leads to accelerated atherosclerosis: role for Nox2 NADPH oxidase.

Insulin resistance underpins the progression of type 2 diabetes mellitus and leads to a collection of risk factors for the development of atherosclerosis. Whether or not insulin resistance at a whole body level per se leads to accelerated atherosclerosis is unclear. To answer this question we generated atherosclerosis prone mice with whole body insulin resistance secondary to haploinsufficiency of the insulin receptor (IR+/-) deficient in ApoE-/- (IR+/-/ApoE-/-). IR+/-/ApoE-/- and ApoE-/- littermates had similar weight, lipids and glucose tolerance at baseline. After 12 weeks Western high cholesterol diet, IR+/-/ApoE-/- had significantly more atherosclerosis in the thoracoabdominal aorta and at the level of the aortic sinus than ApoE-/- littermates. Excess Nox2 NADPH oxidase (Nox2) derived superoxide has been suggested to underpin diabetes related atherosclerosis. In IR+/-/ApoE-/- we examined the effect of inhibiting Nox2 using genetic or pharmacological approaches on the development of atherosclerosis. To genetically delete Nox2 we generated IR+/-/ApoE-/-/Nox2-/y and to inhibit Nox2 pharmacologically we treated IR+/-/ApoE-/- with the peptide Nox2 inhibitor gp91dstat. IR+/-/ApoE-/-/Nox2-/y had significant disruption of the aortic wall with increased thoracoabdominal atherosclerosis when compared to IR+/-/ApoE-/-/Nox2+/y littermates. Inhibition of Nox2 using gp91dstat reduced atherosclerosis in the thoracoabdominal aorta of IR+/-/ApoE-/-. Whole body insulin resistance accelerates the development of atherosclerosis. Genetic inhibition of Nox2 leads to disruption of the aortic wall in IR+/-/ApoE-/- mice with accelerated atherosclerosis whereas pharmacological Nox2 inhibition reduces atherosclerosis in IR+/-/ApoE-/- without disruption of the arterial wall.