Dilated Left Ventricle Research Articles

MitraClip Procedure in Advanced Heart Failure and Severe Mitral Regurgitation: Case Report and Literature Review

Mitral regurgitation (MR) is a common valvular disorder often seen in a severely dilated left ventricle (LV) and reduced LV function. In chronic heart failure (HF), severe functional MR increases preload, wall tension, LV workload, and worsening prognosis. The MitraClip device offers a percutaneous treatment option in HF, although its safety and efficacy in advanced and acute HF remain a gray zone. We present a successful case of the emergent MitraClip intervention in a patient with advanced HF and review the relevant literature.

Double-blind comparison study on the reliability of binary assessment of left ventricular systolic function and dimensions between standard echocardiogram and handheld echocardiogram

Abstract Rationale Left ventricular systolic function parameters have considerable prognostic importance, but demand for echocardiographic examinations is greater than supply. The market availability of handheld echographs provides greater access to low-cost summary echocardiographic evaluation. Purpose of the study The purpose of the study is to compare in a double-blind manner the binary concordance ( yes/no) of an examination done with a handheld ultrasound and a standard echocardiographic examination on four parameters referred to the left ventricle ( LV) on the same patient 4 days apart. Method Thirteen volunteer cardiologists who had performed at least 1000 echocardiograms blindly performed on patients not known to them an evaluation with a handheld ultrasound machine and reported the result on a card stating the presence or absence in an eye-based manner of 4 conditions: LV dilatation, reduced LV systolic function ( left ventricular ejection fraction LVEF< 55%), presence of left ventricular segmental kinetics alterations. The two echocardiographic examinations were performed at a maximum time interval of two days and in the absence of any new procedures on the patient between the two examinations. The time taken for each examination was timed. A statistical analysis with Choen’s Kappa test was performed. Results A total of 107 examinations were performed on 86 patients, whose characteristics are shown in Table Number 1. The average number of examinations per cardiologist was 8.9 with a minimum of 5 examinations and a maximum of 10. There was excellent concordance on the VS dilatation parameter ( kappa 0.85, SE 0.05, 95% CI 0.77 to 0.99), with a number of 4 false positives and 0 false negatives; the ability to detect the presence of reduced global left ventricular systolic function was also excellent ( kappa 0.9 SE 0.04 95% CI 0.82 to 0.99). Concerning left ventricular hypertrophy there was a high percentage ( 22%9 of false negatives), referring to mild degree of LV hypertrophy, with concordance however ( kappa 0.42 SE 0.08 CI 95% 0.26 to 0.59); on segmental kinetics there was 9% false positives and no false negatives with fair concordance ( kappa 0.55 SE 0.09 95% CI 0.37 to 0.73). Results are summarized in table 2. Conclusions Qualitative assessment on left ventricular systolic function parameters with a handheld ultrasound machine compared with a standard echocardiographic examination is reliable for the recognition of left ventricular dilatation and dysfunction. This may have considerable use of the examination as a filter or screening for the recognition of relevant heart disease.

Inflammation clashing onto myocardial susceptibility: a tale of two rare diseases – a case report

Abstract Background Sarcoidosis is a rare inflammatory disease characterized by the presence of myocardial noncaseating granulomas. Heart failure, conduction abnormalities and/or life-threatening arrhythmias are the main manifestations of cardiac sarcoidosis (CS). Cardiac magnetic resonance (CMR) plays a major role in the diagnostic suspicion of cardiac involvement in sarcoidosis. However, late gadolinium enhancement (LGE) patterns are non-specific, and one should consider alternative or additional aetiologies for myocardial disease. Case Summary We report the case of a 40-year-old male with a past medical history remarkable for pulmonary and cutaneous sarcoidosis, presenting with asymptomatic premature ventricular contractions and severe left ventricle (LV) dilation and moderately reduced systolic function. CT-angiography excluded coronary artery disease. CMR revealed myocardial oedema in the anterior, anterolateral and inferolateral walls and the presence of septal intra-mural and anterior, inferior and lateral sub-epicardial “ring-like” LGE. He had elevated inflammatory plasma biomarkers. NT-proBNP was 110pg/mL and high sensitivity-troponin T was 20ng/dL. Positron emission tomography computed tomography scan showed increased myocardial uptake consistent with inflammatory disease. Endomyocardial biopsy was normal. Thus, a presumptive diagnosis of isolated CS was made, and immunosuppression therapy was initiated, with full LV function recovery. Given the “ring-like” LGE pattern we recommended genetic testing, which identified a deletion in the dystrophin gene, classified as likely pathogenic. Discussion This case highlights the contemporary diagnostic pathway for primary cardiomyopathies, emphasizing the increased likelihood of genetically-influenced myocardial vulnerability to continuous harm when coupled with an acquired precipitant of myocardial damage. We describe a case of CS likely superimposed on a genetic myocardial substrate.

A clinical challenge of cardiomyopathies: Beyond the heart

Introduction: The relation between the cancer and the heart is diverse. It can be affected all parts of the heart directly or indirectly caused by the systemic manifestation of the cancer or by cancer therapy. Paraneoplastic dermatomyositis and tumor lysis syndrome (TLS) are two examples of systemic manifestations of cancer. Being systemic, the cardiovascular system can be affected. Heart failure and arrhythmias are the main cardiac manifestations. Case Report: A 68-year-old man with a recent diagnosis of diffuse large B-cell lymphoma waiting to begin chemotherapy, and paraneoplastic dermatomyositis, presented at the emergency department (ED) with palpitations and dyspnea with a week of evolution. At the physical examination, he presented with pulmonary edema and the novo rapid atrial fibrillation. Also, an Nt-pro BNP of 8957 pg/mL, and echocardiography with severe dilated left ventricle, with a severe reduced ejection fraction. Already in the ward, the patient developed a spontaneous TLS. The etiological interpretation was that paraneoplastic dermatomyositis and TLS were the triggers of atrial fibrillation (AF). Then, the combination of them was responsible for development of the dilated cardiomyopathy (tachymyocardiopathy). The chemotherapy regimen was changed to R-CEOP (Rituximab, cyclophosphamide, etoposide, vincristine sulfate, and prednisone). Conclusion: This clinical case perfectly shows how the world of cardiomyopathies can be challenging and hard to understand all the complexity of the patients.

Clinical profile of dilated cardiomyopathy in children enrolled in chronic cardiac care: a decade review in a sub-Saharan African tertiary center

BackgroundDilated cardiomyopathy (DCM) is a myocardial disease characterized by a dilated left ventricle (LV) and reduced LV systolic function. The clinical profile of DCM is not well studied in Africa with no reports from Ethiopia. This study aimed to describe the clinical profile of DCM and the factors associated with its clinical outcome in a tertiary center.ResultsThis study included 75 DCM patients, males 52%. The median age at DCM diagnosis was 18 months (Interquartile range/IQR: 7–46). The major DCM clinical presentations were cough, 84%, fast breathing, 64% and shortness of breath, 56%. The median left ventricular systolic ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) at diagnosis were 30% (IQR: 24–36) and 14% (IQR: 11–18), respectively. The majority don’t have a cause labeled or documented, 81.3% while HIV and anthracycline-related DCM accounted for 6.7% each. Concerning outcomes, the majority didn’t show any clinical status change or were static, 62.7% while one-third, 32%, showed improvement. The case fatality rate in this series was 5.3% [4] (95% CI: 1.47–13.1). The presence of severe acute malnutrition (wasting) at presentation, p 0.017; the latest LV systolic function (LVEF, p 0.000 and LVFS, p 0.000) and the use of enalapril, p 0.017, were associated with DCM clinical outcome.ConclusionBoys in their second birth year were most affected by DCM. The major DCM presentations were a mix of respiratory and cardiac symptoms with severely depressed LV systolic function. Nutritional status at presentation, recent LV systolic function and enalapril use were associated with DCM clinical outcome. Timely nutritional assessment, treatment and support, and enhanced HF medical treatment are recommended to improve DCM clinical outcomes.

Abstract 4134712: Pheochromocytoma-Induced Cardiomyopathy Requiring Mechanical Support with Ejection Fracture Recovery Following Surgical Resection

Introduction: Pheochromocytomas are catecholamine-secreting tumors that arise from chromaffin cells of the adrenal medulla. The annual incidence is approximately 0.8 per 100,000 persons, though this is an underestimate given a high percentage diagnosed at autopsy. Classically, patients present with episodic headache, sweating, and tachycardia, however, pheochromocytomas can be associated with cardiomyopathy secondary to the catecholamine excess. We present an unusual case of pheochromocytoma-induced cardiogenic shock highlighting an excellent use of mechanical circulatory support with Impella and Extracorporeal Membrane Oxygenation (ECMO) bridging to surgical intervention resulting in left ventricular ejection fraction (LVEF) recovery. Case Description: A 49-year-old female with past medical history of asthma initially presented to an outside hospital for palpitations, chest pain, and hypertension. Transthoracic echo (TTE) showed preserved left ventricle ejection fraction (LVEF) while cardiac MRI showed a LVEF of 43% with dilated left ventricle and diffuse global hypokinesis consistent with a dilated cardiomyopathy. She underwent a coronary angiogram demonstrating nonobstructive CAD. She was then discharged with readmission a month later at our hospital for chest tightness, palpitations, vomiting, weakness, and dizziness. Repeat TTE showed a drop in LVEF to 10-15%. She progressed to cardiogenic shock requiring BiPAP and inotrope initiation, with progressive shock and hypotension ultimately requiring Impella 5.5 and venoartrial ECMO. Abdominal imaging was notable for 4.7 x 4.2 cm right adrenal nodule and further workup with serum and urine metanephrines confirmed pheochromocytoma. While supported, the patient underwent right adrenalectomy with subsequent wean of mechanical circulatory support and biventricular recovery on TTE. Discussion: Pheochromocytoma-induced heart failure is a rare but potentially life-threatening complication from excess catecholamine effects on the myocardium. Pheochromocytomas should be considered in the evaluation of idiopathic heart failure even in the absence of symptoms related to catecholamine excess. Early detection, pharmacological management, and surgical resection may prevent progression of myocardial remodeling. Mechanical circulatory support can be a valuable adjunct in managing refractory heart failure in these patients by providing temporary hemodynamic stabilization while awaiting definitive tumor resection.

Abstract 4139169: Treatment with methotrexate associated with LDL-like nanoparticles prevents the development of left ventricular fibrosis in a spontaneously hypertensive rat model

Introduction: Systemic arterial hypertension (SAH) can lead to left ventricle (LV) fibrosis and ventricular dysfunction. Methotrexate (MTX) associated with lipid nanoparticles (LDE) increases the cellular uptake of MTX by ninety-fold, which leads to therapeutic efficacy and reduces drug toxicity. Previously, treatment of rats with myocardial infarction with LDE-MTX decreased LV fibrosis and prevented ventricular dysfunction. The aim was to test LDE-MTX to preclude the development of cardiac damages caused by hypertension in spontaneously hypertensive rats (SHR). Methods: Twenty-four male rats with six-week-old were allocated in 3 groups: Control (CT): Wistar-Kyoto rats injected with saline; SHR: treated with LDE only and SHR-LDE-MTX: treated with LDE-MTX (1mg/Kg/week, I.P.). After 20 weeks of treatment, echocardiography, morphometry and protein expression were performed in the LV. The data were analyzed by ANOVA with Turkey’s post-test or Kruskal-Wallis test with Dunn's post-test. Linear regression was used to evaluate potential relationships. Results: Compared to CT, the two SHR groups showed dilation (increase in systolic and diastolic diameter); hypertrophy (increased thickness of the posterior wall) and systolic dysfunction (decreased ejection and shortening fractions). Furthermore, the SHR group showed increased LV fibrosis in both the interstitial region and the papillary muscle, possibly resulting from increased of type I collagen content. Treatment of SHR with LDE-MTX had no effect on LV dilation, hypertrophy or systolic dysfunction. However, LDE-MTX decreased LV fibrosis of the interstitial region and the papillary muscle. In addition, LDE-MTX increased the expression of MMP-2, and increased the bioavailability of intracellular adenosine, via increased expression of the adenosine A3 receptor. There was a negative correlation between the expression of the adenosine A3 receptor with interstitial fibrosis (r2=-0.31, p=0.03) and papillary muscle (r2=-0.47, p=0.03), indicating that the increased bioavailability of intracellular adenosine also contributed to the decrease in LV fibrosis in SHR. Conclusion: In SHR, treatment with LDE-MTX reduced LV fibrosis, possibly by modulating MMP-2 expression and increasing the bioavailability of intracellular adenosine, via the adenosine A3 receptor. These results suggest a therapeutic role for LDE-MTX in patients with LV fibrosis and heart failure caused by SAH, to be explored in future clinical studies.

Abstract 4131128: Cardiomyocyte-specific Deletion of Creg1 Impairs Autophagy and Leads to Age-dependent Dilated Cardiomyopathy

CREG1 is a small glycoprotein predominantly localized in the endolysosomal system. In mouse heart, CREG1 expression increases with age. We previously observed cardiac hypertrophy and ventricular non-compaction in a small percentage of constitutive Creg1 knockout mice during the neonatal stage. To elucidate the physiological function of CREG1 in the heart, we generated cardiomyocyte-specific Creg1 knockout (cm Creg1 KO) and knock-in (cm CREG1 KI) mice by crossing Creg1 fl/fl and Rosa hCREG1/hCREG1 with Myh6-Cre mice, respectively. By 6 months of age, the cm Creg1 KO mice developed severe myocardial interstitial fibrosis. Echocardiography at 10 months revealed markedly dilated left ventricles and significantly reduced ejection fractions. All the cm Creg1 KO mice succumbed to heart failure between 10-12 months, while Creg1 fl/fl control littermates exhibited no obvious cardiac abnormalities. Necropsy of deceased cm Creg1 KO mice showed increased heart-to-body weight ratios, enlarged cardiac chambers, and left atrial thromboses. Electron microscopy revealed sparse and elongated myofibers, scant and bizarre-shaped mitochondria, empty cytoplasm, and increased interstitial collagen accumulation. The cm CREG1 KI mice exhibited better endurance to nutritional deprivation than Rosa hCREG1/hCREG1 littermate controls. In sharp contrast to cm Creg1 KO hearts, cm CREG1 KI and Rosa hCREG1/hCREG1 control hearts displayed very mild fibrosis at 8 months, suggesting that CREG1 overexpression may confer cardioprotective effects. In cultured cardiomyocytes, CREG1 colocalizes with the autophagosome marker LC3B following serum deprivation. Immunofluorescence microscopy demonstrated a marked reduction of LC3B puncta in cm Creg1 KO hearts. Analysis of autophagic flux using CAG-RFP-EGFP-LC3 transgenic mice and immunoblotting indicated that the absence of CREG1 impairs both autophagosome formation and degradation, whereas knock-in of CREG1 enhances these autophagic processes. These findings suggest that CREG1 promotes autophagy and protects the heart from age-dependent dilated cardiomyopathy.

Abstract 4124430: Calcinosis Cutis and Heart Failure---A Rare Manifestation Which Should Never Be Ignored!

Introduction: Heart failure can be a manifestation of underlying immune mediated myopathies like dermatomyositis/polymyositis which can present in broad range of clinical manifestations and sometimes dermatologic lesions can be the only manifestation of these underlying pathologies without typically involving the muscle weakness. Calcinosis cutis is the deposition of calcium salts in the skin and subcutaneous tissue. There are five subtypes of calcinosis cutis, dystrophic, metastatic, idiopathic, iatrogenic and calciphylaxis. Case summary: 70-year-old female was evaluated for bilateral lower extremity swelling. Past medical history was significant for Graves’ disease, atrial fibrillation, mechanical aortic valve on warfarin, hypertension, hyperlipidemia, ascending aortic aneurysm. Work up showed BNP of 4700 pg/ml with normal cardiac enzymes. Transthoracic echocardiogram revealed newly reduced ejection fraction of 25—30% with severely dilated left ventricle. Patient refused cardiac catheterization. Nuclear stress test showed no evidence of ischemia. Patient was started on guideline directed medical therapy and biventricular Implantable cardioverter defibrillator device was placed as per cardiology recommendation. Six months later patient developed multiple calcinosis cutis lesions on abdominal wall requiring surgical excisions. Endocrine work up including PTH, serum Ca level was normal, however creatin kinase level was high normal (150 U/L). Serum aldolase was ordered which was found to be elevated(25U/L). Muscle biopsy was performed as per recommendations of rheumatology which was diagnostic of dermatomyositis. Patient was started on high dose steroids and methotrexate and eventually IV immunoglobulins as per rheumatology recommendation. Follow up echocardiogram revealed improved ejection fraction to 40--45% with resolution of any further lesion of calcinosis cutis afterwards. Conclusion: Cardiac involvement such as congestive heart failure can be a part of presentation of underlying untreated myopathies. Calcinosis cutis can be the only clinical manifestation of dermatomyositis affecting heart. Etiology of calcinosis cutis in patients with heart failure should be worked up properly. Dystrophic calcinosis cutis is the subtype associated with underlying autoimmune connective tissue diseases.

Abstract 4144514: Human Immunodeficiency Virus Associated Cardiomyopathy- A Rare Cause of Heart Failure With Reduced Ejection Fraction in Era of Highly Active Antiretroviral Therapy

Introduction: Human Immunodeficiency Virus Associated Cardiomyopathy (HIVAC) is characterized by left ventricular (LV) systolic or diastolic dysfunction with or without LV dilatation and heart failure symptoms. The introduction of antiretroviral therapy (ART) has changed the fulminant systolic heart failure presentation of HIV myocarditis to diastolic heart failure. We present a unique case of dilated cardiomyopathy in a young patient without advanced HIV illness which has rarely been documented in the literature. This is a rare presentation of HIVAC in the post-ART era. Case Report: A 32-year-old male with a past medical history (PMH) of the human immunodeficiency virus (HIV) presented with complaints of new onset worsening shortness of breath and lower extremity edema for four weeks. He was diagnosed with HIV seven years ago and was not compliant with ART. Laboratory testing showed a cluster of differentiation 4 (CD4) 823 and HIV load 2550. Myocarditis was ruled out by normal troponin levels and no new changes on the electrocardiogram (ECG). Transthoracic echocardiogram (TTE) showed dilated left ventricle (LV), LV global hypokinesis, LV ejection fraction (LVEF) 10-15%, dilated right ventricle, biatrial dilation, moderate to severe mitral regurgitation, severe tricuspid regurgitation, pulmonary artery (PA) systolic pressure 73 mmHg and no pericardial effusion. Coronary angiography was negative for coronary artery disease (CAD). The patient was started on carvedilol and outpatient evaluation for a left ventricular assistance device. Discussion: Systolic dysfunction in patients with HIVAC carried a poor prognosis in the pre-ART era and was common in patients with elevated c-reactive protein (CRP), tobacco use, and previous myocardial infarction (MI). After the advent of ART, systolic dysfunction is rare and replaced by diastolic cardiomyopathy in the setting of ART use. Diagnosis is usually by excluding other etiologies and biopsy is not necessarily required. Management is usually guideline-directed medical therapy (i.e. beta blocker, renin-angiotensin-aldosterone antagonists, sodium-glucose cotransporter-2) and device-based therapy but there is still data lacking to assess its benefit.

Vaccination targeting senescence-associated transmembrane protein alleviated cardiovascular pathology in the mice

Abstract Introduction Accumulation of senescent cells is observed in various organs including vasculature, heart and white adipose tissue with age, and known to become a substrate of pathophysiology of various cardiovascular-metabolic diseases. We have previously developed a vaccine to eliminate senescent cells, so-called "senolytic vaccine" by targeting Glycoprotein Nonmetastatic Melanoma Protein B (GPNMB) as a cellular-senescence-associated cell surface protein. We have demonstrated that GPNMB senolytic vaccine could remove senescent cells and alleviate the pathology cardiovascular-metabolic diseases. Senescence-associated adhesion molecule 1 (SAAM-1) is also known as a cell-surface membrane to increase its expression during cellular senescence in endothelial cells as well as the development of cardiovascular diseases. Here, we identified SAAM-1 as another senescence antigen and created a vaccine to eliminate senescent cells by targeting SAAM-1. Purpose This study was purposed to evaluate the efficacy of SAAM-1 vaccine for the treatment of cardiovascular diseases in mice models. Methods As a pressure overload-induced heart failure (HF) model, C57BL/6N wild type (WT) mice were underwent transverse aortic constriction (TAC) or sham opretaion at 13 weeks of age. SAAM-1 or control vaccination were given at 8 and 10 weeks of age before operation. Echocardiography examination was conducted two weeks after TAC operation, followed by tissue sampling 3 weeks after the examination. As an atherosclerosis model, ApoE KO mice were subjected to a high-fat diet (HFD) starting at 4 weeks of age. Vaccination of ApoE KO mice was administered at 8 weeks of age with SAAM-1-vaccine or control-vaccine, followed by sacrifice 4 weeks later for further analysis. ApoE-KO mice were also crossed with p16-mediated Luciferase expressing mice (p16-Luc mice) and subjected to generation of atherosclerosis model. Results SAAM-1 expression was significantly increased in left ventricle (LV) in TAC mice but its increase was suppressed by SAAM-1 vaccination. Interestingly, both worsening systolic function and dilatation of LV by pressure overload were significantly alleviated by SAAM-1 vaccination. Furthermore, expression level of senescent markers including p16 and p21, as well as several inflammation markers were increased in failing heart along with development of cardiac fibrosis, but SAAM-1 vaccine could significantly attenuate this pathological change. In ApoE KO mice, SAAM-1 vaccine decreased expression level of several inflammation markers in the mice, along with a decreasing p16 signal in the aorta. Conclusions Targeting SAAM-1 for vaccination would be a novel and promising approach to alleviating age-related cardiovascular disease.

Endothelial NRG-1 knock-out causes left ventricle dilation in the presence and absence of angiotensin II administration

Abstract Introduction Neuregulin-1 (NRG-1) is a growth factor derived from endothelial cells and belongs to the epidermal growth factor (EGF) family. While NRG-1 is expressed by various cell types, including epithelial cells, glial cells, neurons, and myocytes, the primary source of NRG-1 is considered to be the endothelium. NRG-1 exerts its effects through the EGF receptors ERBB2, ERBB3, and ERBB4. Upon ligand binding, these receptors dimerize and become phosphorylated, leading to downstream signaling that impacts tissue proliferation, differentiation, and survival. The biological role of NRG-1 is intricate due to its isoforms and differential expression across distinct tissue types. In our study, we investigated the impact of endothelial NRG-1 knock-out (KO) on the heart, both in the presence and absence of angiotensin II (ANGII) treatment. ANGII serves as a trigger for NRG-1 upregulation. Methods C57BL/6N-VE-cad-cre-ERT2 mice were crossbred with C57BL/6N-NRG F/F mice, enabling endothelial-specific NRG-1 knockout (KO) using a tamoxifen-inducible promoter. At eight weeks of age, C57BL/6N-VE-cad-cre-ERT2-NRG F/F mice received tamoxifen (1 mg) or vehicle injections for nine consecutive days intraperitoneally (i.p.) to induce the KO. Two days after injection, osmotic minipumps were subcutaneously implanted, releasing a stable dose of angiotensin II (ANGII) at a rate of 400 ng·kg·min⁻¹ for a four-week period. Sham operations served as controls (SHAM). In the final week of treatment, high-frequency ultrasound imaging was performed to assess cardiac function and dimensions. After four weeks of ANGII treatment, mice were sacrificed, and organs were weighed and harvested for further molecular analysis. Results High-frequency ultrasound revealed left ventricle dilation in the absence of endothelial NRG-1, both in ANGII-treated and SHAM-treated mice. This was demonstrated by a significant increase in systolic and diastolic left ventricle internal diameter (LVID) in the endothelial NRG-1 KO groups compared to their respective controls. Additionally, systolic and diastolic LV volume (LV-vol) was significantly increased in the endothelial NRG-1 KO groups, regardless of ANGII treatment. Notably, there was no difference in LVID and LV-vol between SHAM and ANGII-treated groups in the presence of endothelial NRG-1, indicating that LV dilation is primarily due to the absence of endothelial NRG-1 rather than ANGII. Furthermore, heart weights of the endothelial NRG-1 KO mice were significantly increased compared to the control groups, as shown in Figure 1. Conclusion Our study demonstrates that endothelial NRG-1 KO leads to LV dilation, suggesting a crucial role for endothelial-secreted NRG-1 in maintaining normal LV function in adulthood. Further research is needed to fully understand the precise role of NRG-1 in LV homeostasis.

Regadenoson stress echocardiography: a road ahead

Abstract Introduction Drugs used in stress echocardiography (SE) have important limitations due to side effects and contraindications. Since its approval in 2008, Regadenoson has seen a significant increase in usage. This is largely attributed to its good safety profile and diagnostic accuracy, making it the preferred drug for stress tests in many European centers. However, despite its expanding use and major advantages, current guidelines don't place it as the first choice for SE, probably because the reported experience with this drug remains limited. The aim of the present study was to assess the safety and short-medium term prognosis of patients who underwent Regadenoson SE. Methods Retrospective observational study. Patients who underwent Regadenoson SE between 2017 and 2023 were included. Safety was assessed by monitoring immediate adverse effects following Regadenoson infusion and the need for using an antidote (Aminophylline). A positive test result was defined by the occurrence of any of the following: wall motion abnormalities, left ventricle dilatation, electrocardiographic changes or symptoms of ischemia. During the follow up, we registered the incidence of ischaemic events (admission for unstable angina, acute myocardial infarction (AMI) or cardiovascular (CV) death) and other CV events such as admission for heart failure (HF) and stroke. Additionally, we evaluated patients in both groups who underwent coronary angiography (by computerized tomography or coronary catheterization) during the follow up period. The groups with negative SE (NSE) and positive SE (PSE) were compared. Results The total number of patients was 344, with a median follow up of 29 months. Basal population characteristics and events by group (NSE and PSE) are shown in Figure 1. We needed to use the antidote in only one case, because of ventricular bigeminism, with no other major adverse effects reported. SE was positive in 37 (11%) patients. In this group, patients were more likely to present ischaemic events (16% vs. 3%, p<0.01) and admissions for HF (24% vs. 5%, p <0.01), compared to the NSE one. In those who underwent coronary angiography, revascularization was needed in 14 patients of the PSE group, and only in 7 of the NSE group (38% vs 2%, p < 0.05). The indications for these last cases were persistent angina in 5 patients (2 of them with history of coronary artery disease) and revascularization following an AMI in 2 patients. (Figure 2). Conclusions The probability of an ischaemic event after a negative Regadenoson SE remains very low, unlike positive studies. Regadenoson SE showed to be both safe in assessing ischemic cardiomyopathy and very useful for its prognostic value. These findings encourage its expanding use in the stress echo lab.

Diagnostic performance of semi-quantitative echocardiographic evaluation in patients with aortic regurgitation: implications for clinical practice

Abstract Background In current practice, screening for severe aortic regurgitation (AR) relies on qualitative and semi-quantitative echocardiographic parameters. No information is given on the diagnostic performance of each of these parameters. Objectives The purpose of this study was to investigate the diagnostic performance of semi-quantitative echocardiographic parameters in discriminating moderate from severe AR. Methods This single-center retrospective cohort study included 102 consecutive patients with chronic isolated moderate or severe AR. Patients were divided between severe and moderate AR using a combination of left ventricle (LV) dilatation, Proximal Isovelocity Surface Area (PISA) echocardiographic method and cardiovascular magnetic resonance (CMR). Receiver operator characteristic (ROC) curve analysis was performed to assess the diagnostic accuracy of vena contracta width (VC), pressure half-time (PHT) and diastolic flow reversal in descending aorta (DFR). Results Threshold value VC > 6mm provided a low sensitivity (40.4%) and an excellent 88.9% specificity for the diagnosis of severe AR. For PHT, the value < 200ms provided a poor sensitivity (2.0%) and an excellent 100% specificity. For DFR, the value ≥ 0.2m/s provided a low sensitivity (37.8%) and a good 78.6% specificity. These 3 parameters have a good positive predictive value (PPV) > 80% and a poor negative predictive value (NPV) < 40%. The area under the curve for the diagnosis of severe AR was 0.72, 0.72 and 0.59 for VC, PHT and DFR, respectively. Conclusion Our study demonstrates that the semi-quantitative parameters VC, PHT and DFR are highly specific but poorly sensitive for diagnosing severe chronic AR. They can rule in severe AR but in presence of intermediate values, they are insufficient to rule out severe AR.Venn diagramDiagnostic performance

The rare association of congenital glaucoma, giant melanocytic nevus, alopecia, and hypospadias in an Egyptian child with neurofibromatosis type 1: a case report

BackgroundNeurofibromatosis type 1 (NF1) is a multisystem genetic disorder that commonly involves skin, nerves, and skeletal system with increased neoplastic predisposition. This disease has been rarely associated with multiple congenital anomalies. Herein, we describe an Egyptian child with NF1 and coexistent bilateral congenital glaucoma, giant congenital melanocytic nevi (GCMN), alopecia, and hypospadias.Case presentationA 2.5-year-old boy presented with developmental delay, back swelling, and multiple congenital anomalies. His father and two sisters were known to have NF1. The child was diagnosed with bilateral primary congenital glaucoma at the age of 3.5 months and underwent trabeculectomy with mitomycin C therapy. Examination at the age of 5 months revealed marked hypotonia, multiple GCMN, scanty café-au-lait macules, left upper eyelid plexiform neuroma and trichomegaly, hypertrichosis of left eyebrow, hypertelorism, depressed nasal bridge, left frontal scalp alopecia, and distal penile hypospadias. At the age of 8 months, brain imaging depicted a markedly dilated left lateral ventricle, and he underwent ventriculoperitoneal shunt surgery. The child developed back swelling at the age of 2.5 years, and a spinal magnetic resonance image showed bilateral multiple spinal neurofibromas in the paraspinal region with intraspinal extensions. A whole exome sequencing identified a heterozygous missense variant NM_001042492.3:c.1466A > G (NP_001035957.1:p.Tyr489Cys) in NF1 gene.ConclusionsThe present case report adds to the knowledge of the phenotypic spectrum and variability of NF1 by reporting the association of multiple unusual congenital anomalies. Importantly, such congenital anomalies could be the first presenting features in patients with NF1 since cafe´-au-lait macules and other typical diagnostic criteria may not be apparent in the neonatal period and early infancy. Accordingly, NF1 should be considered in newborns with congenital glaucoma, GCMN, scalp alopecia, and hypospadias.

Silent severe aortic regurgitation due to blunt chest trauma: ignore it at your peril—a case report

Abstract Background Blunt chest trauma (BCT) presenting to the emergency department is common and may cause life-threatening cardiac complications. Whilst complications causing haemodynamic instability are generally detected promptly, others may present late with long-term consequences. We describe a rare, serious complication of BCT presenting five years after a road traffic accident (RTA). Case summary A 23-year-old man was incidentally found to have a murmur. Past history was notable only for BCT with rib fracture sustained in a RTA 5 years prior. Examination revealed a hyperdynamic pulse, loud decrescendo diastolic murmur, and Duroziez’s sign over the femoral arteries. Echocardiography showed severe valvular aortic regurgitation (AR) from a hole in the left coronary cusp and holodiastolic flow reversal in the descending aorta. The left ventricle (LV) showed marked dilatation in diastole, mild dilatation in systole, and preserved systolic function. The aorta was normal. Severe AR was attributed to his previous BCT, with AR causing subsequent LV dilatation. He underwent aortic valve replacement (AVR) with rapid recovery. He remains well, and his echo shows a well-functioning AVR with normalization of LV dimensions. Discussion Aortic regurgitation following BCT is rare but well-recognized, most often resulting from RTAs. Only a third of cases are diagnosed acutely. In others, lack of haemodynamic instability means that emergency echocardiography is not routinely performed, such that this may go unrecognized with long-term consequences. Clinicians should be aware of possible valve damage following BCT. Prompt echocardiography should be routinely performed for all BCT at initial presentation, even without haemodynamic instability.

P098 CARDIAC REMODELING IN MICE TREATED WITH SODIUM OXALATE AND AORTIC STENOSIS

Background: Cardiovascular Diseases are one of the main global public health problems, with increasing mortality due to population aging and Hypertension (HTN). HTN is a risk factor for other diseases, such as aortic stenosis, renal dysfunction, and cardiac hypertrophy (CH). The hemodynamic overload caused by HTN affects the heart and kidneys, but the exact mechanisms of these alterations are not fully understood. Experimental models help study these mechanisms; however, a well-established model of CH with cardiorenal dysfunction does not yet exist. Objective: to evaluate whether the combination of cardiac hypertrophy, induced by transverse aortic constriction (TAC), and renal injury, induced by soluble sodium oxalate (OXA), can be a new model of CH with cardiorenal dysfunction. Methods: Male C57BL mice were randomized as follows: SHAM, receiving saline or OXA solution, and TAC, receiving saline or OXA solution. Echocardiography, direct blood pressure (BP) recording, metabolic cage, histology were performed to evaluate cardiac and renal function, hemodynamics, autonomic modulation, and baroreflex. Results: The TAC+OXA group showed the highest systolic BP(SBP) (SBP: SHAM: 122±5.24 vs. TAC+OXA: 160±5.24 mmHg, p<0.01), increased double product (DP) (DP: SHAM: 64.65±4.76 mmHg/bpm vs. TAC: 89.53±5.85 mmHg/bpm, p=0.02), significant reduction in autonomic modulation (RMSSD: OXA: 12.5±1.8 vs. TAC+OXA: 2.8±0.2 ms, p<0.01) and reflex tachycardia, eccentric hypertrophy, and worse renal function. The TAC group showed eccentric hypertrophy, increased BP variability (SD-SBP: SHAM: 2.97±0.07 mmHg vs. TAC: 5.63±0.57 mmHg, p≤0.01), diastolic dysfunction, and dilated left ventricle in diastole. The OXA group showed increased autonomic modulation and heart rate variability, renal damage characterized by inflammation, proximal tubule damage, and interstitial fibrosis when associated with TAC. All treated groups showed a significant reduction in reflex tachycardia. Conclusion: Transverse aortic constriction combined with OXA gavage is a model of CH with renal dysfunction, as the combination caused more significant renal damage, systemic hypertension, decreased autonomic modulation and baroreflex sensitivity, and eccentric hypertrophy with subsequent LV diastolic dysfunction.

Abstract We147: The Utility of Cardiopulmonary Exercise Testing (CPET) Amongst Male and Female athletes to Differentiate Between Physiological Left Ventricular Enlargement and Mildly Depressed Resting Systolic Function and Athletic Individuals with Dilated Cardiomyopathy.

Background: Athletes frequently reveal a dilated left ventricle (LV),some also demonstrate a co-existent mildly depressed LV ejection fraction, raising the possibility of mild dilated cardiomyopathy (DCM). The maximal oxygen consumption(VO2max) is a valuable tool for assessing fitness, largely determined by cardiac output. References ranges derived from the general population, may have limitations when assessing athletes with primary myocardial disease. This study investigated the role of VO2max and VO2max predicted (V02pred) to differentiate between physiological LV dilatation and athletic individuals with DCM in male and female athletes. Methods: 147 male and 35 female athletes with dilated LV(mean age 35.4years, 34.5 years respectively) underwent a 25watt cycle ergometer continuous ramp protocol. 75% males and 67% females participated in endurance sports, remaining participating in mixed sports. 52 had mild DCM, 62 defined as healthy control athletes(dilated LV) and 68 were Grey zone (dilated LV and mildly depressed LVEF) Results: DCM males (N=39) revealed a lower mean VO2max than male control (N=46), 34.9ml/kg/min and 48ml/kg/min respectively (p value <0.001). DCM females(N=13) showed lower VO2max of 29.9ml/min/kg than female control (N=16) who revealed similar values to male controls (48 ml/kg/min)(p value <0.001). 62 male Grey zones and 6 female Grey zone revealed lower VO2max than controls 43.1ml/min/kg and 34.1ml/min/kg respectively. DCM females had lower VO2pred than control females 119% and 161% respectively but significantly higher than their male counterparts, means of 106% and 123% respectively (p value <0.001). Male and female grey zones had lower mean VO2pred than controls, 121% and 106% respectively. Higher VO2max of ≥38ml/kg/min and VO2pred of ≥120% gave a sensitivity, specificity of 84.7% and 77%respectively to differentiate healthy athletes and athletic DCMs in males and females. Only41.1% Grey zone athletes were able to achieve above these thresholds. Conclusion: Female athletes with dilated LV may reveal supranormal VO2max which can equal their male counterparts. Furthermore, athletic females with physiological or pathological LV dilatation can reveal higher VO2pred than male athletes. Most athletic DCM individuals show lower CPET parameters than controls athletes but can still achieve greater than normal measurements seen in healthy general population. VO2 may have a role in assisting in differentiating healthy athletes from athletic DCM.

Abstract We065: Sex Differences in Autoimmune Signatures After Myocardial Infarction in Mice

Introduction: Myocardial infarction (MI) is caused by ischemic injury to the left ventricle (LV), leading to an inflammatory response, scar formation, and loss of LV function. The role of the autoimmune (AI) response during chronic MI, such as B cell activation and autoantibody production, is not well understood. As AI disease is much more prevalent in females, we hypothesized that female mice are more susceptible to MI-induced development of AI signatures. Methods: Permanent MI was induced by left coronary artery ligation in adult male and female C57BL/6J mice for 7, 28, or 56 days. LV function was tracked using echocardiography (VEVO 3100). Cytokines were measured by qPCR. LV IgG and IgM antibody deposition was measured by immunofluorescence. Plasma IgG and IgM were measured by ELISA, and plasma autoantibodies (AABs) (IgG and IgM subclasses) were measured with an autoantigen (AAN) array. Results: In both sexes, MI led to progressive LV hypertrophy, dilation, and wall thinning. MI increased spleen mass in D7, 28, and 56 females, but decreased spleen mass in D28 and 56 males. LV infarct cytokines (IL-1β, IL-6, IL-18, IFN-γ, TNF, CCL2, IL-10) were increased at D7, while IL-6 and IL-18 remained elevated at D28 and 56 to a higher degree in females. Several cytokines in the remote LV were increased in females relative to males, including TNF, IL-6, CCL2, and IL-18. Splenic cytokines were also differentially expressed between sexes, with IL-1β, IL-12a, IL-10, IFN-γ, IL-18, CCL2, and IL-4 increased in females at several time points. Infarct IgG and IgM deposition occurred in both sexes, but to a higher degree in females. Remote IgG and IgM deposition occurred at D56 in both sexes. For plasma AABs, we detected 34 AANs against which IgG AABs were significantly elevated (p<0.05) at D56 in females vs 9 in males, and 30 IgM AABs vs 1 in males. Of note, anti-IL-6 IgM AABs were elevated in D56 females (9.8±0.8-fold), likely due to persistently elevated IL-6 in the female infarct and remote LV vs males. Total levels of plasma IgM were increased only in females at D56 (1.79±0.15-fold). Conclusions: MI promotes development of AI signatures which is exacerbated in females, including increased spleen mass, LV and splenic cytokines, LV infarct and remote IgG and IgM antibody deposition, increased plasma IgG and IgM AABs, and increased total levels of plasma IgM. Targeting the AI response may be a viable option for treating chronic MI outcomes, particularly in females.

Pulmonary artery banding for cardiomyopathy in young children: First trial in China.

Heritable dilated cardiomyopathy (DCM) or DCM associated with congenital or acquired left ventricular diseases carries a significant mortality risk. Pulmonary artery banding (PAB) has been proposed as an alternative to heart transplantation. This study aimed to delineate the clinical development, ventricular reverse remodelling, and functional regeneration of the dilated left ventricle, presenting as a pioneering approach in China. This prospective study was initiated in November 2021, involving paediatric patients with a significant dilated left ventricle and preserved right ventricle who underwent surgical PAB. The baseline characteristics and clinical information during follow-up were collected. Seven patients (five boys) with a median age of 240 (148, 1028) days have been included thus far. No procedural or follow-up mortality was observed. The modified Ross functional class improved from treatment to follow-up of 348 (200, 629) days, and the median left ventricular ejection fraction increased from 27.0 (15.0, 34.0) % before surgery to 61.0 (52.0, 68.0) % (P<0.05); the median left ventricular end-diastolic diameter and corresponding Z-scores decreased from 43.0 (40.0, 55.0) mm [+9.4 (+7.7, +11.7)] to 33.0 (29.0, 39.0) mm [+1.8 (+1.3, +3.8)] (P<0.05). Functional regeneration of the left ventricle was observed in five patients. Three of them underwent balloon dilation of the PAB to relieve excessively elevated right ventricular pressures. The application of PAB should adhere to strict criteria. Initial results are promising for infants and even toddlers with a dilated left ventricle and limited probability of spontaneous recovery. PAB can be an alternative when there is a shortage of donor transplants and assist devices, especially for low- and middle-income countries.