Cardiac Vessels Research Articles

Sex Differences in a Real-World Registry Examining Coronary Lithotripsy for Calcified Lesions

Intravascular lithotripsy (IVL) has established as a safe and effective treatment for coronary artery calcification (CAC). This study aimed to evaluate sex-related differences in the treatment with IVL in a real-world, all-comers international registry. Patients undergoing IVL between May 2019 and February 2024 were enrolled from the BENELUX-IVL registry. Patients were divided into men and women groups. Efficacy endpoints included device success (delivery of the IVL-balloon across the target lesion and administration of therapy without related complications), technical success (TIMI 3 flow and residual stenosis <30% by quantitative coronary analysis and/or fluoroscopically) and procedural success (composite of technical success with absence of in-hospital major adverse cardiovascular events (MACE: cardiac death, myocardial infarction or target vessel revascularization). Safety endpoints were IVL-related complications and MACE at one-year follow-up. 454 patients (73±9.0 years) were treated with IVL, comprising 342 (75%) men and 112 (25%) women. More women presented with acute coronary syndrome (41% in men vs 54% in women; p=0.014) and aorto-ostial lesions (17% in men vs. 29% in women; p=0.009), while the Syntax score (23.5±14.2 in men vs. 17.1±1.0 in women; p<0.001) was higher in men. Rates of device success (97% vs. 98%; p=1.000), technical success (90% vs. 91%; p=0.821) procedural success (90% vs. 88%; p=0.749), IVL-related complications (1% vs 2%; p=0.362) and one-year MACE rates (12% vs 17%; p=0.456) were comparable. In conclusion, despite differences in clinical presentation and lesion types, IVL seems to be safe and effective for both sexes across various clinical and anatomical scenarios.

Cardiac lymphatics undergo distinct remodeling during hypertrophic and nonhypertrophic pregnancy.

Lymphatic vessels of the heart undergo dynamic remodeling in response to physiological and pathological cardiovascular events such as development, adult cardiac maintenance, and injury repair. During pregnancy, the cardiovascular system undergoes physiological changes to meet the increased demand for blood supply to the fetus. These extensive physiological changes make pregnancy and delivery a high-risk period in a woman's life. However, whether and how cardiac lymphatics change during pregnancy is largely undefined. Therefore, we used whole mount immunofluorescent labeling and quantitative morphometric analysis to characterize the changes in cardiac lymphatic vasculature during pregnancy using two genetically distinct inbred mouse strains, C57BL/6J and BALB/cJ. When compared with age-matched, nonpregnant C57BL/6J control mice, the hearts of C57BL/6J dams in late pregnancy [gestation day 17.5 (G17.5)] undergo physiological hypertrophy. However, there were no significant changes in the cardiac lymphatic vasculature. In contrast, BALB/cJ mice do not exhibit pregnancy-induced cardiac hypertrophy at G17.5 compared with age-matched, nonpregnant mice. Yet interestingly, the cardiac lymphatic vasculature of pregnant BALB/cJ dams undergoes extensive morphological changes, including decreased lymphatic length, number of end points, and vessel branch-point junctions on the ventral side of the heart. These findings underscore the complexity of genetic and physiological factors that contribute to the heterotypic remodeling of cardiac lymphatics during late pregnancy.NEW & NOTEWORTHY Cardiac lymphatics remodel in response to physiological and pathological stresses. This study is the first to investigate cardiac lymphatic vessel changes during pregnancy. BALB/cJ mice, which do not undergo pregnancy-induced cardiac hypertrophy, show decreased lymphatic length, number of end points, and junctions on the ventral side during pregnancy. In contrast, C57BL/6J mice, which undergo pregnancy-induced cardiac hypertrophy, had no such changes. These findings underscore the complexity of genetic and physiological factors contributing to cardiac lymphatic remodeling.

Age-related decline in cardiac lymphatic vessels causes cardiac edema and macrophage accumulation

Abstract As life expectancy has significantly increased, age-related diseases, particularly cardiovascular diseases, have become a primary global cause of death. Aging has multiple effects on the heart and is one major risk factor for cardiovascular diseases. The microcirculation has been extensively studied in this context. However, the contribution of the lymphatic vasculature, which is responsible for draining excessive tissue fluid and immune cells, to age-related pathologies is currently unknown. To address the effect of aging on lymphatics, we examined lymphatic capillary density using LYVE1 and PDPN staining in old (&amp;gt;20 months) and young (3 months) mouse hearts. Aging induced a significant reduction in lymphatic vessel density in the sub-endocardial and –epicardial area of aged left ventricles, in both genders (0.28±0.08 fold and 0.68±0.03 fold; p&amp;lt;0.05), while the right ventricle showed no change. Notably, dilation of (pre-) collector lymphatics was observed in in old hearts, indicating, together with the lymphatic vessel reduction, a lymphatic drainage dysfunction. Indeed, cardiac aging was accompanied by increased numbers of CD68+ macrophages, accumulation of the plasma protein fibrinogen and amyloid into the interstitial space. Moreover, we observed a significant increase in tissue oedema in the aged hearts (p&amp;lt;0.05). The decline in lymphatic vessels was associated with a reduced expression of Vegfc (0.72±0.04 fold; p&amp;lt;0.005), a major lymphatic growth factor, in 20-month-old mouse hearts compared to their 3-month-old counterparts. To establish a causal link between lymphatic dysfunction and age-related cardiac changes, we examined hearts from 3-month-old Flt4;Prox1-CreERT2 mice, that have defective lymphatic vessels. Also these mice, despite their young age, displayed fibrinogen (1.32±0.08 fold; p&amp;lt;0.05) and CD68+ macrophage (1.58±0.08 fold; p&amp;lt;0.05) accumulation compared to wildtype littermates. Apart from these, other age-related changes, such as tendency to cardiac hypertrophy, were also observed; this is currently under further investigation. Likewise, blocking VEGFC signaling in young mice by overexpressing the soluble form of Flt4 impaired cardiac lymphatic capillary density (0.62±0.06 fold; p&amp;lt;0.01), leading to increased macrophage and fibrinogen accumulation (1.69±0.09 fold, 4.60±0.30 fold; p&amp;lt;0.001), suggesting that a decline of lymphatics induces some of the age-associated pathologies. Finally, we addressed whether restoring Vegfc expression in old mice can rescue age-related cardiac impairment. Overexpressing Vegfc via AAV9 in aged mice restored cardiac lymphatic density by 3-fold and reduced CD68+ macrophage density by 1.6-fold, without effect on fibrinogen accumulation. In conclusion, our study demonstrates an age-related reduction in left ventricular lymphatic density, cardiac edema and inflammation. Vegfc overexpression prevented the age-dependent decline of lymphatic vasculature and reduced cardiac inflammation.

Long-term outcomes following DCB vs. DES for ISR treatment

Abstract Background The-long term outcomes of patients with in-stent restenosis (ISR) presenting with chronic coronary syndrome (CCS) are not well studied. Purpose This study aims to investigate the outcomes of patients with drug-eluting stents (DES)-ISR presenting with CCS undergoing percutaneous coronary intervention (PCI) with drug-coated balloons (DCB) or thin strut-DES. Methods Consecutive patients from the Dragon-Registry with CCS and DES-ISR who underwent PCI with thin-DES or paclitaxel-DCB for DES-ISR were enrolled. Primary outcome was target lesion revascularization (TLR). Secondary outcomes were target vessel revascularization (TVR) and device-oriented composite endpoint [DOCE: cardiac death, TLR or target vessel myocardial infarction (TV-MI)]. Propensity-score matching was used to adjust for baseline differences. Results A total of 846 patients were included in the pooled analysis, of whom 381 (45%) were treated with a thin-DES and 465 (55%) with paclitaxel-DCB. Patients who received thin-DES compared with those who received paclitaxel-DCB had lower crude rates of TLR (hazard ratio [HR], 0.50 [95% CI, 0.34-0.74], P&amp;lt;0.001) TVR (HR, 0.56 [95% CI, 0.39-0.86], P&amp;lt;0.001) and DOCE (HR, 0.63 [95% CI, 0.45-0.88], P=0.007).The incidence of cardiac death and TV-MI were similar in both groups. After matching, the observed differences persisted in terms of TLR (HR, 0.54 [95% CI, 0.33–0.88], P=0.013), TVR (HR, 0.57 [95% CI, 0.41–0.80], P=0.009), and DOCE (HR, 0.65 [95% CI, 0.42–0.99], P=0.046) between the thin-DES and DCB group, respectively. Conclusions In long term observation in patients with CCS undergoing PCI of ISR, the use of thin-DES is associated with reduced rates of TLR, TVR and DOCE compared with patients treated with DCB.

Influence of pathophysiological patterns of coronary artery disease on the safety and efficacy of percutaneous coronary intervention

Abstract Background Impaired blood flow after PCI, reflected by low FFR, portends a worse prognosis. Prior to intervention, pressure gradient distributions offer insights into the likelihood of subsequent PCI success. The pullback pressure gradient (PPG) serves as a quantifiable measure of CAD patterns: values approximating 1 signify focal disease, while values approaching 0 suggest diffuse disease. This study aimed to assess the impact of pathophysiological CAD patterns on the safety and efficacy of PCI. Methods PPG Global was a prospective, investigator-initiated, multicenter study, single-arm that enrolled patients with at least one lesion with an FFR ≤ 0.80 scheduled to be treated by PCI. The study enrolled 1004 patients (1057 vessels). A standardised physiological assessment was performed, including online PPG calculation from manual FFR pullbacks. CAD patterns were defined as predominantly focal or diffuse disease based on the median PPG value. The study was powered to ascertain the predictive capacity of PPG for optimal PCI results (defined as FFR≥0.88 after PCI) as assessed by the AUC. Immediate PCI outcomes were assessed using post-PCI FFR and CFR. Following PCI, biomarkers (troponin) were collected. An independent clinical events committee adjudicated periprocedural myocardial infarction. The assessment of peri-procedural myocardial infarction (MI) adhered to the criteria outlined in the 4th Universal Definition of Myocardial Infarction. Target vessel failure (TVF) was defined as cardiac death, myocardial infarction and target vessel revascularisation. Results One thousand and four patients with 1057 vessels were included. The mean FFR was 0.68 ± 0.12, PPG 0.62 ± 0.17, post-PCI FFR 0.87 ± 0.07, and post-PCI CFR was 3.19 ± 1.93. PPG was significantly correlated with the change in FFR after PCI (r=0.65, 95% CI: 0.61-0.69, p&amp;lt;0.001) and showed an area under the curve of 0.82 (95% CI: 0.79-0.84) to predict optimal revascularisation. Suboptimal FFR (&amp;lt;0.88) after an angiographically successful PCI occurred in 471 vessels (53.5%) and was significantly higher in patients with diffuse disease (37.1% vs 74.0%, p&amp;lt;0.001). The change in CFR was sixfold higher in patients with high PPG (delta CFR focal 1.18 ± 1.94 and diffuse 0.19 ± 1.52, p&amp;lt;0.001). The rate of in-hospital TVF was similar between patients with focal vs diffuse disease (5.1% vs 8.5%, p=0.060). The incidence of periprocedural MI was significantly higher in patients with diffuse disease (5.9% vs 9.8%, p=0.050; OR 1.83, 95% CI 1.02 to 3.34). Conclusions Pathophysiological CAD patterns distinctly affect the safety and efficacy of PCI. PCI in focal disease was associated with improved physiological outcomes and a lower rate of periprocedural myocardial infarction compared to diffuse disease. Quantifying PPG before intervention reliably predicted post-PCI FFR. Further investigation through a randomised trial is warranted to explore the potential advantages of a PPG-guided PCI strategy.PPG and Revascularisation OutcomesPPG and FFR correlation Pre and Post-PCI

Short vs Standard Duration Dual Antiplatelet Therapy after Percutaneous Coronary Intervention with New-Generation Drug-Eluting Stents: A Meta- Analysis

Objective: In patients with coronary artery disease, dual antiplatelet therapy (DAPT) is recommended after percutaneous coronaryintervention, but the duration is still debated. This meta-analysis compared short-duration (1 to 3 months) to standard-time (twelve months) double antiplatelet treatment in patients who received coronary intervention with new generation drug eluting Stent.Methodology: To conduct this examination, we methodically looked at PubMed, Cochrane CENTRAL, Embase, and Web of Sciencedatabases for randomized controlled trials, evaluating varying durations of double antiplatelet treatment following new generation stents implantation from July to September 2023. Seven randomized controlled trials were included witha total of 22,945 patients. The primary efficacy endpoint was the incidence of Major adverse cardiovascular events, such as cardiac mortality, heart attack, stent coagulation, and target vessel revascularization; while the safety endpoint was the incidence major bleeding. Secondary endpoints were major adverse cardiovascular and cerebro-vascular complications, any bleeding, and net adverse cardiovascular incidence for a year after stent implantation.Results: Short-time DAPT was linked to a significantly less incidence of major bleeding (0.8% vs 1.5%), any bleeding (2.5% vs 4.2%)and NACE (2.5% vs 4.2%) compared to standard duration of DAPT. No significant variation was noticed among the two groups regarding major adverse cardiovascular events (4.1% vs. 4.2%) and acute cardiovascular and cerebrovascular incidents (4.7% vs. 4.8%). Short-duration DAPT in patients with acute coronary syndrome was linked with decreased risk of bleeding and net adverse cardiovascular events.Conclusion: Short-duration (1- or 3-month) DAPT significantly lowers bleeding risk and reduces net clinical adverse events without increasing ischemic risk, making it a reasonable choice for people with new-generation drug eluting stents, particularly those with highbleeding risk or recent surgery.

Current application and results of the combined use of intravascular lithotripsy and rotational atherectomy for the treatment of calcified coronary lesions

Abstract Background Intravascular lithotripsy (IVL) and rotational atherectomy (RA) might be used simultaneously (Rotatripsy) to treat calcified lesions during percutaneous coronary intervention (PCI), though data on the effectiveness and sequence of their use is limited. Purpose To identify indicators for the use of Rotatripsy and to assess its safety and success rates, both acutely as at one-year follow-up. Methods Patients undergoing PCI with IVL and RA across six centers in two European countries from May 2019 to December 2023 were included. Demographic, clinical, procedural and follow-up data were collected. Angiographic and intracoronary imaging (ICI) data were analyzed centrally. Efficacy endpoints included device success (delivery of the RA-burr and IVL-balloon across the target lesion and administration of therapy without related complications), technical success (TIMI 3 flow and residual stenosis &amp;lt;30% by quantitative coronary analysis) and procedural success (composite of technical success with absence of in-hospital major adverse cardiovascular events (MACE: cardiac death, myocardial infarction or target vessel revascularization). Safety endpoints comprised rotatripsy-related complications and MACE at one-year follow-up. Results A total of 114 patients (75±9 years, 78% male) underwent rotatripsy for 120 lesions. Patients presented with an ACS in 58(51%) cases and chronic coronary syndrome in 56(49%). The left anterior descending artery(n=66, 55%) was the most frequently treated target vessel, with diverse lesions being addressed, including bifurcations(30%), ostial(18%), CTO(7%) and in-stent(12%) lesions. The mean burr size was 1.5±0.2mm with a maximum rotational speed of 171±15k rpm and burr/vessel ratio of 0.46±0.2. IVL involved an average of 68±25 pulses and a balloon size of 3.5±0.5mm. The predominant used sequence of rotatripsy was RA followed by IVL(n=106, 88%). Among these cases, IVL was electively combined with RA in 68(57%) lesions, and used for balloon underexpansion(n=37, 31%) and stent crossing failure after RA(n=1, 1%). Additionally, IVL served as bail-out strategy after RA and stenting in 10(8%) and preceded RA in 4(3%) lesions, particularly when balloon/stent delivery failed after IVL. After rotatripsy, stents were implanted in 116(97%) lesions and drug-eluting balloon used in 3(3%). ICI was utilized in 69(58%) target lesions. Device, technical and procedural success were 97%, 94% and 93%, respectively. Therapy-related complications occurred in 4 patients(4%), and included two(2%) coronary perforations, one(1%) dissection and one(1%) burr entrapment. At one-year follow-up (present in 77(67%)), MACE was observed in 7(6%). Conclusions Rotatripsy demonstrated efficacy across diverse clinical and anatomical settings, with the majority of procedures electively employing RA before IVL. High success rates and low complication rates were observed, with few patients experiencing MACE at one-year follow-up.

A retrospective study on real world, 2-stent left main bifurcation PCI using DK crush technique with IVUS guidance - a single center experience

Abstract Objectives The aim of this study is to investigate clinical outcome of the IVUS guided 2-stent bifurcation strategy using DK crush technique performed in a complex Left Main (LM) bifurcation lesions defined according to DEFINITION study in our local setting. We seek to assess the composite endpoint of target vessel failure (TVF) at 9-12 months. Methods All patients underwent IVUS guided 2-stent Bifurcation PCI with DK crush technique for complex LM bifurcation lesions defined by the DEFINITION criteria performed in a heart institute from 1.1.2019 to 31.7.2023 were included..Patient baseline characteristics, post-procedural and 12-months follow-up outcomes including cardiac death,myocardial infarction (MI),rate of target vessel failure (TVF),rate of stent thrombosis (ST) and major adverse coronary event (MACE) were analysed.Exclusion criteria are patients age &amp;lt;18 years and previous stenting in the target vessel Results A total of 50 patients were included in this analysis. Mean age was 64.3±9.1 years with predominant males (n= 38, 76%).Majority were hypertensive (n=37, 74%) and diabetes mellitus accounted for 32 (64%) cases.Patients with pre-existing coronary artery disease were 39 (78%) cases. 40% presented with history of recent myocardial infarction (MI), 12% had new onset angina and 6% had heart failure. Pre-existing chronic renal failure (18%) and history of CVA (2%). Among chronic renal failure cases, 50% had eGFR &amp;lt;50 during index procedure.Additionally, previous PCI was performed in 22 cases (44%) and 2 previous CABG cases included (4%).Majority of the cases were performed as staged elective procedure ( n=45, 90%) and others were indicated for ACS ( n=5, 10%). Radial approach was predominantly preferred with 25 cases (50%), where additional 5 cases (10%) were converted to femoral approach due to severe radial spasm. Among these 50 cases, 1 case required additional PCI to CTO LAD and mid LCX, while 7 cases (14%) had calcified lesions requiring scoring / cutting balloons and atherectomy device utilization for adequate lesion preparation prior to bifurcation stenting.All 50 patients received combination of both aspirin and a P2Y12 inhibitors for 12 months. Follow up done at at 30-day, 60-days and 1 year after the index procedure.Clinical follow-up were available in 46 (92%) patients only.4 cases were lost to follow up due to logistic reasons. At 1 year follow-up, cardiac death occurred in 5 (10.9%) patients, out of which 3 (6.5%) cases were cardiac related and 2 (4.4%) are non-cardiac. Major adverse cardiac events (MACE) and target vessel failure (TVF) occurred in total 4 (8.7%) cases, where 3 (6.5%) cases resulted in cardiac death and 1 (2.2%) case had MI and clinically driven target lesion revascularization. Conclusion Our experience demonstrates that IVUS guided, upfront 2-stent Bifurcation PCI using DK crush technique for complex bifurcation lesions is effective and safe with a low MACE and TLR rate at 1 year follow-up.

Dextrocardia with complete atrioventricular block—the right clinical approach to pace a heart on the right hemithorax: a case report

BackgroundA heart positioned on the right side of the thorax can be more a complex situation than it seems, also the potentially associated congenital cardiopathies are variable. In this regard, patients with dextrocardia presenting with complete atrioventricular block require a thorough anatomical investigation to map the veno-arterial system and potential cardiovascular defects before proceeding with a permanent pacing procedure.Case presentationA 73-year-old Caucasian woman with no significant medical history presented with syncope. Physical examination showed regular heart sounds with an average heart rate of 35–40 beats per minute and no other relevant physical findings. Chest X-rays revealed a heart positioned in the right hemithorax. A standard electrocardiogram revealed complete atrioventricular block with junctional escape rhythm at nearly 35–40 beats per minute. A transthoracic echocardiogram showed a mirror image dextrocardia without any other remarkable abnormalities. Venogram performed using the left peripheral cephalic vein showed normal venous return into the right atrium positioned on the left side. Surgical intervention consisted of permanent dual chamber pacemaker implantation using the left subclavian vein. Discussion is provided based on the relevant medical literature outlining different potential scenarios with associated cardiac and major vessels abnormalities.ConclusionThis case highlights an atypical presentation of atrioventricular block in a patient with dextrocardia and situs inversus, for whom a successful dual-pacemaker implantation procedure was performed.

Independent role of atherosclerotic plaque composition and extension in predicting the risk of cardiac events: a CLIMA substudy.

To investigate two different approaches to determine patient risk to develop cardiac events: the burden of coronary atherosclerosis, as assessed by the Gensini score, and plaque morphology, as assessed by intracoronary optical coherence tomography (OCT). We assessed the Gensini score and OCT features of plaque vulnerability in 847 patients from the CLIMA registry. Patients were divided into four Gensini quartiles. The main study endpoint was the 1-year composite of cardiac death, myocardial infarction (MI) and/or target vessel revascularization (TVR). A total of 56 patients (6.6%) experienced the one-year main composite endpoint. The composite endpoint was significantly affected by the Gensini score (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.11-1.81, p = 0.005), with a low incidence in the first Gensini quartile (Q1 1.3%) and a higher incidence in the remaining groups (Q2 8.3%, Q3 8.9% and Q4 8.3%). At the multivariable analysis, the combined four OCT criteria (HR 6.4, 95%CI 3.0-13.7, p < 0.001), thin fibrous cap (HR 2.9, 95%CI 1.7-5.0, p < 0.001), lipid arc > 180° (HR 2.1, 95%CI 1.2-3.6, p = 0.010), minimum lumen area < 3.5 mm2 (HR 1.7, 95%CI 1.01-3.0, p = 0.047) and the Gensini score (HR 1.4, 95%CI 1.1-1.8, p = 0.017) were independent predictors of the main composite endpoint. In this post-hoc analysis of the CLIMA study, the burden of coronary atherosclerosis as assessed by the Gensini score and OCT plaque characteristics were independent predictors of cardiac events. Patients with the largest atherosclerosis burden and with plaque vulnerability by OCT were at the highest risk of poor outcome. Clinicaltrials.gov identifier: NCT02883088.

In ovo toxico-pathological effects of medicinal plants used against coccidiosis on chicken embryos development and hatchability

TOXICO-pathological effects of herbal plants have always been a major concern, but little information is provided on the toxico-pathological effects of medicinal plants used against coccidiosis. This study aimed to assess the histopathological effects of Carica papaya seeds (CPS), Azadirachta indica leaves (AIL), and Sarcocephalus latifolius root (SLR) used as coccidiostat in traditional poultry farms with various doses using the chick embryo model. A total of 420 Sasso breeder eggs at ED4 of incubation were inoculated with the extract of these plants following a 3×4 factorial design with 3 plant extracts (CPS, AIL and SLR) and 4 inoculation doses (0, 25, 50 and 100 mg/kg egg-weight). From ED6 to ED19, the weights of the albumen and embryo were recorded, and the weights of ED19 embryo organs such as liver, heart, kidney, and lungs were measured. Additionally, histopathological lesions were examined. The results indicated that the presence of various phytoconstituents such as alkaloids, phenolics, flavonoids, tannins, saponins, coumarins, steroids, and triterpenes with statistically significant free-radical-scavenging ability differed among the plant extracts (p < 0.0001). Toxico-pathological examination revealed a dose-dependent slight toxicity (p < 0.0001) of the Azadirachta indica leaves extract compared to the other plants. Additionally, the relative organ weight showed kidney hypertrophy (p = 0.001) and liver hypertrophy (p = 0.0001), as well as dilation of hepatic and cardiac vessels. The conclusion drawn was that chicken embryos are more susceptible to in ovo inoculation with Azadirachta indica leaves compared to Carica papaya seeds and Sarcocephalus latifolius root.

Disease-Specific Alteration of Cardiac Lymphatics: A Review from Animal Disease Models to Clinics.

For many years, the significance of cardiac lymphatic vessels was largely overlooked in clinical practice, with little consideration given to their role in the pathophysiology or treatment of cardiac diseases. However, recent research has brought renewed attention to these vessels, progressively illuminating their function and importance within the realm of cardiovascular science. Experimental studies, particularly those utilizing animal models of cardiac disease, have demonstrated a clear relationship between cardiac lymphatic vessels and both the pathogenesis and progression of these conditions. These findings have prompted a growing interest in potential therapeutic applications that specifically target the cardiac lymphatic system. Conversely, while clinical investigations into cardiac lymphatics remain limited, recent studies have begun to explore their identification through specific surface markers, as well as the expression dynamics of lymphangiogenic factors. These studies have increasingly highlighted associations of lymphatic dysfunction with inflammation and fibrosis, both of which negatively impact cardiac function and remodeling across various pathological states. Despite these advances, comprehensive reviews of the current knowledge regarding the cardiac lymphatic vasculature, particularly within specific disease contexts, remain scarce. This review aims to address this gap by providing a detailed synthesis of existing reports, encompassing both animal model research and studies on human clinical specimens, with a special focus on the role of cardiac lymphatic vessels in different disease states.

Clinical impact of deep learning-derived intravascular ultrasound characteristics in patients with deferred coronary artery

Prognostic markers for long-term outcomes are lacking in patients with deferred (nonculprit) coronary artery lesions. This study aimed to identify the morphological criteria for predicting adverse outcomes and validate their clinical impact.Using deep learning models, we extracted geometrical parameters and maximal attenuation (or calcium) burden index (ABI-max or CBI-max) from the intravascular ultrasound (IVUS) images of nonculprit vessels in 1115 patients. The endpoints included cardiac death, myocardial infarction, and target vessel revascularization of nonculprit vessel.Cardiac death occurred in 27 (2.4 %) patients at 3 years and 39 (3.5 %) patients at 5 years. At 5 years, the cardiac death-free survival rate was significantly lower with ABP-max ≥11.37 % vs. < 11.37 % (90.0 % vs. 98.7 %), CBI-max ≥13.40 % vs. < 13.40 % (92.8 % vs. 98.4 %), and percent atheroma volume ≥ 51.35 % vs. < 51.35 % (94.0 % vs. 97.7) (all log-rank p < 0.001). The independent predictors of 5-year cardiovascular mortality were age (hazard ratio [HR] 1.21), female sex (HR 0.33), history of heart failure (HR 6.06), chronic kidney disease (HR 18.28), ABI-max (HR 1.04), and CBI-max (HR 1.05). The independent determinants of 5-year target vessel revascularization of nonculprit vessel were fractional flow reserve (HR 0.95 per 0.01 increase), minimal lumen area (HR 0.63), and plaque burden (HR 1.15).In patients with nonculprit coronary artery lesions, a large burden of attenuated or calcified plaques predicted cardiac mortality, while IVUS geometry was associated with repeat revascularization. Thus, deep learning–based IVUS analysis of the whole target vessel may help clinicians identify high-risk lesions.

Structural and functional fetal cardiac imaging using low field (0.55 T) MRI.

This study aims to investigate the feasibility of using a commercially available clinical 0.55 T MRI scanner for comprehensive structural and functional fetal cardiac imaging. Balanced steady-state free precession (bSSFP) and phase contrast (PC) sequences were optimized by in utero studies consisting of 14 subjects for bSSFP optimization and 9 subjects for PC optimization. The signal-to-noise ratio (SNR) of the optimized sequences were investigated. Flow measurements were performed in three vessels, umbilical vein (UV), descending aorta (DAo), and superior vena cava (SVC) using the PC sequences and retrospective gating. The optimized bSSFP, PC and half-Fourier single shot turbo spin-echo (HASTE) sequences were acquired in a cohort of 21 late gestation-age fetuses (>36 weeks) to demonstrate the feasibility of a fetal cardiac exam at 0.55 T. The HASTE stacks were reconstructed to create an isotropic reconstruction of the fetal thorax, followed by automatic great vessel segmentations. The intra-abdominal UV blood flow measurements acquired with MRI were compared to ultrasound UV free-loop flow measurements. Using the parameters from 1.5 T as a starting point, the bSSFP sequences were optimized at 0.55 T, resulting in a 1.6-fold SNR increase and improved image contrast compared to starting parameters, as well as good visibility of most cardiac structures as rated by two experienced fetal cardiologists. The PC sequence resulted in increased SNR and reduced scan time, subsequent retrospective gating enabled successful blood flow measurements. The reconstructions and automatic great vessel segmentations showed good quality, with 18/21 segmentations requiring no or minor refinements. Blood flow measurements were within the expected range. A comparison of the UV measurements performed with ultrasound and MRI showed agreement between the two sets of measurements, with better correlation observed at lower flows. We demonstrated the feasibility of low-field (0.55 T) MRI for fetal cardiac imaging. The reduced SNR at low field strength can be effectively compensated for by strategically optimizing sequence parameters. Major fetal cardiac structures and vessels were consistently visualized, and flow measurements were successfully obtained. The late gestation study demonstrated the robustness and reproducibility at low field strength. MRI performed at 0.55 T is a viable option for fetal cardiac examination.

Technological Advances Are Associated With Better Clinical Outcomes of Percutaneous Coronary Intervention inPatients With Unprotected Left MainDisease.

Few large-scale studies have evaluated the effectiveness of percutaneous coronary intervention (PCI) technological advances in the treatment of patients with unprotected left main coronary artery disease (LM-CAD). We aim to identify independent factors that affect the prognosis of PCI in patients with unprotected LM-CAD and to assess the impact of PCI technological advances on long-term clinical outcomes. A total of 4512 consecutive patients who underwent unprotected LM-CAD PCI at Fuwai Hospital from 2004 to 2016 were enrolled. Multivariable Cox proportional hazards model was used to identify which techniques can independently affect the incidence of major adverse cardiac events (MACEs; a composite of cardiac death, myocardial infarction, or target vessel revascularization). The incidence of 3-year MACEs was 9.0% (406/4512). Four new PCI techniques were identified as the independent protective factors of MACEs, including second-generation drug-eluting stents (hazard ratio [HR], 0.61 [95% CI, 0.37-0.99]), postdilatation (HR, 0.75 [95% CI, 0.59-0.94]), final kissing balloon inflation (HR, 0.78 [95% CI, 0.62-0.99]), and using intravascular ultrasound (HR, 0.78 [95% CI, 0.63-0.97]). The relative hazard of 3-year MACEs was reduced by ≈50% with use of all 4 techniques compared with no technique use (HR, 0.53 [95% CI, 0.32-0.87]). PCI technological advances including postdilatation, second-generation drug-eluting stent, final kissing balloon inflation, and intravascular ultrasound guidance were associated with improved clinical outcomes in patients who underwent unprotected LM-CAD PCI.

Cardiac Lymphatics and Therapeutic Prospects in Cardiovascular Disease: New Perspectives and Hopes.

The lymphatic system is the same reticular fluid system as the circulatory system found throughout the body in vascularized tissues. Lymphatic vessels are low-pressure, blind-ended tubular structures that play a crucial role in maintaining tissue fluid homeostasis, immune cell transport, and lipid absorption. The heart also has an extensive lymphatic network, and as research on cardiac lymphatics has progressed in recent years, more and more studies have found that cardiac lymphangiogenesis may ameliorate certain cardiovascular diseases, and therefore stimulation of cardiac lymphangiogenesis may be an important tool in the future treatment of cardiovascular diseases. This article briefly reviews the development and function of cardiac lymphatic vessels, the interaction of cardiac lymphatic vessels with cardiovascular diseases (including atrial fibrillation, coronary atherosclerosis, and heart failure), and finally discusses the therapeutic potential of targeted cardiac lymphatic therapy for cardiovascular diseases.

Development of a Bmi1+ Cardiac Mouse Progenitor Immortalized Model to Unravel the Relationship with Its Protective Vascular Endothelial Niche.

The adult mammalian heart has been demonstrated to be endowed with low but real turnover capacity, especially for cardiomyocytes, the key functional cell type. The source, however, of that turnover capacity remains controversial. In this regard, we have defined and characterized a resident multipotent cardiac mouse progenitor population, Bmi1+DR (for Bmi1+ Damage-Responsive cells). Bmi1+DR is one of the cell types with the lowest ROS (Reactive Oxygen Species) levels in the adult heart, being particularly characterized by their close relationship with cardiac vessels, most probably involved in the regulation of proliferation/maintenance of Bmi1+DR. This was proposed to work as their endothelial niche. Due to the scarcity of Bmi1+DR cells in the adult mouse heart, we have generated an immortalization/dis-immortalization model using Simian Vacuolating Virus 40-Large Antigen T (SV40-T) to facilitate their in vitro characterization. We have obtained a heterogeneous population of immortalized Bmi1+DR cells (Bmi1+DRIMM) that was validated attending to different criteria, also showing a comparable sensitivity to strong oxidative damage. Then, we concluded that the Bmi1-DRIMM population is an appropriate model for primary Bmi1+DR in vitro studies. The co-culture of Bmi1+DRIMM cells with endothelial cells protects them against oxidative damage, showing a moderate depletion in non-canonical autophagy and also contributing with a modest metabolic regulation.

Comparison of colostrum and milk extracellular vesicles small RNA cargo in water buffalo

Recently, much interest has been raised for the characterization of signaling molecules carried by extracellular vesicles (EVs), which are particularly enriched in milk (mEVs). Such interest is linked to the capability of EVs to cross biological barriers, resist acidification in the gastric environment, and exert modulation of the immune system, mainly through their microRNA (miRNA) content. We characterized the small-RNA cargo of colostrum EVs (colosEVs) and mEVs from Italian Mediterranean buffalo through next generation sequencing. Colostrum (first milking after birth) and milk (day 50 of lactation) were sampled from seven subjects from five farms. ColosEVs and mEVs were subjected to morphological characterization, followed by high-depth sequencing of small RNA libraries produced from total RNA. The main difference was the amount of EV in the two samples, with colostrum showing 10 to 100-fold higher content than milk. For both matrices, miRNA was the most abundant RNA species (95% for colosEVs and 96% for mEVs) and three lists were identified: colosEV-specific, mEV-specific and shared most expressed. Gene ontology (GO) enrichment analysis on miRNA targets highlighted many terms related to the epigenetic, transcriptional and translational regulations across the three lists, with a higher number of enriched terms for colosEV-specific miRNAs. Terms specific to colosEVs were related to “cell differentiation” and “microvillus assembly”, while for mEV “cardiac and blood vessel development” and “mitochondria” emergerd. Immune modulation terms were found for both sample-specific miRNAs. Overall, both matrices carry a similar molecular message in terms of biological processes potentially modulated into receiving cells, but there is significant difference in the abundance, with colostrum containing much more EVs than milk. Moreover, colosEVs carry molecules involved in signal transduction, cell cycle and immune response, as for mEVs and EVs of other previously characterized species, but with a special enrichment for miRNAs with epigenetic regulation capacities. These beneficial characteristics of colosEVs and mEVs are essential for the calf and could also be exploited for the therapeutic purposes in humans, although further studies are necessary to measure the sanitization treatment impact on EV conservation, especially in buffalo where milk is consumed almost exclusively after processing.

Abstract We072: Effects of electronic cigarettes on mouse cardiac lymphatic vessels after TAC surgery

Introduction: Heart failure is a public health concern worldwide. It is known that tobacco smoking is a risk factor of heart failure. Tobacco smoking also causes inflammation reaction and lymphatic dysfunction in the lung. However, the effects of electronic cigarettes (ECIG), as a new method of smoking, on the heart and cardiac lymphatic vessels (lymphatics) are not clear yet. The lymphatic vessels play an important role in maintaining cardiac function by modulating fluid homeostasis and transporting macromolecules. It has been reported that cardiac lymphatic vessel formation limits pressure overload-induced heart failure in C57Bl/6 but not in Balb/c mice. How cardiac lymphatics might contribute to the pathogenesis induced by ECIG is not known. Research Questions: The roles of cardiac lymphatic vessels in responses to ECIG exposure are not investigated. I hypothesize that the toxic effects of ECIG on the heart are partially caused by damaging the cardiac lymphatic vessels. Aim: To determine the effects of ECIG exposure on cardiac lymphatics after Transverse aortic constriction (TAC). Methods: I perform TAC surgery on mice as a heart hypertrophy and chronic heart failure model. Mice after TAC or Sham surgery are treated with different vaping components from ECIG: ECIG, propylene glycol and glycerin (PGVG) as vehicle, and air. After 4 weeks of treatment, hearts were harvested for histological analyses. The lymphatic vessel coverage percentage and morphology were examined by immunostaining. Results: Prior research suggested that genetic background in mice might affect the responses of cardiac lymphatic vessels to TAC-induced heart failure. I have established the TAC model using CD-1 mice. My results showed that CD-1 mice treated with PGVG after TAC do not show a significant difference in cardiac lymphatic vessel density compared to Sham group (p value=0.5951). ECIG treatment also did not affect the lymphatic density significantly compared to PGVG treated mice after sham operation (p value=0.8937). ECIG treated mice after TAC surgery showed a trend of increased lymphatic coverage and more mice are still being processed and will be presented at the conference. Conclusion: PGVG treated CD-1 mice do not show changes in lymphatic vessel density 4 weeks post TAC. Longer time points and more mouse numbers are needed to compare the effects of PGVG and ECIG after TAC induced hypertrophy and heart failure. This research is supported by California TRDRP grant.

Combined assessment of fractional flow reserve, resting full-cycle ratio, and resting ratio of distal coronary to aortic pressure for clinical outcomes

BackgroundFractional flow reserve (FFR) and non-hyperemic indices are invasive standards for evaluating functional significance of coronary stenosis. However, data are limited about outcomes in vessels with concordant and discordant physiological results, particularly with a ratio of distal coronary to aortic pressure (Pd/Pa) at rest. MethodsThis was a single-center, retrospective, observational study. Coronary physiological indices including FFR, resting full-cycle ratio (RFR), and resting Pd/Pa were invasively evaluated in vessels with intermediate coronary artery stenosis. FFR ≤0.80, RFR ≤0.89, and resting Pd/Pa ≤0.92 were considered physiologically positive. Vessels were divided into three groups according to the results of FFR, RFR, and resting Pd/Pa: concordant positive (all positive for FFR, RFR, and resting Pd/Pa), concordant negative (all negative for FFR, RFR, and resting Pd/Pa), and discordant groups. The primary endpoint was target vessel failure (TVF) defined as a composite of cardiac death and target vessel myocardial infarction and unplanned revascularization. ResultsOf 987 vessels included, 311 (31.5 %), 263 (26.6 %), and 413 (41.9 %) were in the concordant positive, discordant, and concordant negative groups. During a median follow-up period of 417 (208–756) days, TVF occurred more frequently in the concordant positive group, followed by the discordant and concordant negative groups (7.7 % vs. 4.6 % vs. 2.4 %, p = 0.004). TVF increasingly accrued during long-term follow-up, while discordant results of RFR and resting Pd/Pa did not result in worse outcomes compared with negative RFR and resting Pd/Pa. ConclusionThe combined assessment of FFR with RFR and resting Pd/Pa stratified TVF risks in vessels with intermediate coronary stenosis.