Severe Left Ventricular Hypertrophy Research Articles

DON’T FORGET ABOUT CARDIAC AMYLOIDOSIS: WHEN RED FLAGS MATTER

Abstract Case Report A 78–year–old man came to our attention for worsening dyspnea, asthenia and frequent lipothymic episodes in the last few weeks. Nothing remarkable was reported in anamnesis except for periodic cardiological check–ups ascribed to hypertensive heart disease and moderate aortic stenosis. Other cardiovascular risk factors were obesity, previous smoking habits and dyslipidemia. A recent 24–hours ECG monitoring revealed slow permanent atrial fibrillation (AF) with 3–seconds pauses, frequent premature ventricular complexes (PVCs) and some PVCs couplets. On arrival, NT–proBNP was elevated (2952 pg/mL), while ECG showed AF with a heart rate of 50/m and low voltages in peripheral leads. Transthoracic echocardiogram revealed a biatrial dilatation, a severe left ventricular (LV) concentric hypertrophy with a preserved LV ejection fraction (EF) and a moderate aortic stenosis. In addition, a restrictive LV filling pattern, a decreased longitudinal myocardial contraction and an apical sparing of longitudinal strain were reported. Invasive coronary angiography was performed with evidence of normal coronary arteries. Given the echocardiographic suspicion of amyloidosis, a 99mTc–Hydroxymethylene diphosphonate (HMDP) scintigraphy was performed, showing a moderate cardiac uptake and an attenuated bone uptake (Perugini Score 2). Serum and urine immunofixation resulted negative. Genetic testing did not find any mutations in Transthyretin (TTR) gene. Therefore, the diagnosis of TTR wild–type amyloidosis was made. Before discharge, putting it all together, we opted to implant a leadless pacemaker in order to protect the patient from life–threatening bradyarrhythmias. Discussion Although it is currently considered rare, there is growing evidence that cardiac amyloidosis may be more common than once thought. First of all, it should be investigated in HFpEF–patients (heart failure with preserved EF) with LV hypertrophy. Despite several red flags (low QRS voltages, conduction disorders, elevated NT–proBNP, severe LV hypertrophy and aortic stenosis) and various medical consultations, our patient had to wait 4 years or more to be diagnosed with cardiac amyloidosis. Inevitably, a diagnostic delay means loss of time in treatment initiation. Earlier diagnosis would enable us to improve our patients’ survival and heart failure hospitalization. Awareness alone is not enough, we must be right on target too.

A LONG QT SYNDROME WITHOUT MANIFESTATION

Abstract A 66–year–old Caucasian woman presented for outpatient evaluation due to elevated blood pressure levels at home (approximately 220/120 mmHg) and a significant family history of long QT syndrome. The index case in the family appeared to be her sister, investigated following an ECG showing markedly prolonged QT interval and a family history of sudden cardiac death. The patient underwent genetic analysis, revealing a positive mutation in KCNQ1. She was currently on treatment with Levotiroxina for recently discovered hypothyroidism.The ECG showed sinus rhythm with a heart rate of 85 bpm, signs of left ventricular hypertrophy, particularly Sokolow (SV1 + RV6 70 mm) and Peguero Lo Presti (SD + SV4 50 mm). The QTc interval was 515 ms (Bazett). Echocardiography revealed severe left ventricular hypertrophy (SIVd 14 mm; PWd 12 mm; LVMi 128 g/m2; RWT 0.5) with normal overall systolic function (EF 60%). No significant valvular pathologies were observed, and the right ventricle appeared normal in size and function.The hypertrophy was attributed to uncontrolled severe arterial hypertension. However, the identification of a prolonged QT interval in a patient with a strong family component (Schwartz score 4, high probability) led to genetic testing, confirming a mutation in KCNQ1. As the patient was asymptomatic with a low risk of major arrhythmias over the next 5 years (1–2–3–LQTS–risk score 2.77%), she entered follow–up and received beta–blocker therapy, specifically nadolol, combined with other antihypertensive medications.This clinical case describes an entire family with LQTS1 (type 1) positive for KCNQ1 mutation, exhibiting phenotypic manifestations distinct from those reported in the literature. Notably, there was a prevalence in females, and the condition was incidentally discovered during a routine checkup conducted for unrelated reasons, without any history of major arrhythmias.Long QT syndrome (LQTS) is characterized by a prolonged QT interval, predisposing individuals to life–threatening arrhythmias leading to syncope and sudden death. Mutations in genes encoding ion channels account for 75% of LQTS cases. LQTS1, associated with a "loss–of–function" mutation in the KCNQ1 gene, represents one of the three genetic subtypes. LQTS1 typically manifests with arrhythmias in childhood, with a male predominance. Adrenergic triggers are crucial precipitants for arrhythmic events

Transcatheter transfemoral aortic valve replacement in a patient with acromegaly and severe left ventricular myocardial hypertrophy. Case report

Main causes of secondary hypertrophic cardiomyopathy include acromegalic cardiomyopathy. Heart damage in patients with the acromegaly is mediated both by the direct action of growth hormone and insulin-like growth factor-1, and increased deposition of collagen and lymphomononuclear cells in the myocardium, which leads to architectural changes, disturbances in fluid and electrolyte balance, severe left ventricular myocardial hypertrophy, diastolic and systolic left ventricular dysfunction and chronic heart failure. This article presents the world's first described observation demonstrating the possibility of successful transfemoral aortic valve repair to a comorbid patient with severe aortic stenosis according to the potential risks caused by the active form of the acromegaly.

Prognostic implications of left ventricular hypertrophy and mechanical function in Fabry disease: A longitudinal cohort study

The prognostic value of different grades of left ventricular hypertrophy (LVH) and left ventricular (LV) mechanical function in Fabry disease is unclear. We aimed to evaluate the association between the severity of LVH, LV mechanical function, and clinical outcomes in Fabry disease. We conducted a retrospective cohort study from a single-center registry of adult patients with Fabry disease. LV mass index (LVMI) was measured by echocardiography. The severity of LVH was categorized by LVMI using the sex-specific cutoff values. LV mechanical function was measured as LV global longitudinal strain (GLS) by speckle tracking analysis. The primary outcome was a composite of major adverse cardiovascular events (MACE) at 5 years, including heart failure hospitalization, sustained ventricular tachycardia, acute ischemic stroke, and all-cause mortality. The study included 268 patients (age 50.4 ± 15.4 years, men 46.6%) with Fabry disease (83.2% IVS4+919G>A mutation) , and 106 patients (39.6%) had LVH. Patients with mild, moderate, or severe LVH had 5-year MACE rates of 7.4%, 10%, and 30.5%, respectively (P< 0.001). Moreover, patients with impaired LV GLS (<14.1%) had a higher 5-year MACE rate than those with preserved LV GLS (32.1% vs. 2.4%, P< 0.001). Severe LVH was an independent predictor of MACE as compared with those without LVH (adjusted hazard ratio, 12.73; 95% confidence interval, 1.3-124.71; P= 0.03), after adjusting for age, sex, hypertension, hyperlipidemia, atrial fibrillation, renal function, average E/e', enzyme replacement therapy (ERT), and LV GLS. Patients with severe LVH and impaired LV GLS had the highest incidence for MACE (log-rank P< 0.05), irrespective of sex, genotypes, and whether receiving ERT or not. Sex-specific grading of LVH by LVMI is practical for risk stratification in patients with Fabry disease, and impaired LV GLS further refines the prognostication.

Circulating microRNA-21-3p in patients with arterial hypertension

Objective — to study changes in the blood plasma levels of microRNA‑21‑3p in patients with arterial hypertension (AH) and their relationship with the characteristics of the course of the disease.&#x0D; Materials and methods. Examinations involved 24 patients with hypertension stage II and degree 2—3 (11 men, 13 women) aged from 42 to 60 years. The control group consisted of 12 practically healthy individuals, age and gender matching. The examinations were carried out in the Department of Hypertension and Kidney Diseases of the GI «L. T. Mala National Therapy Institute of NAMS of Ukraine». The degree, stage of hypertension and the presence of risk factors for cardiovascular diseases (CVD), established CVD and kidney disease were assessed in accordance with current recommendations. All patients underwent general clinical laboratory and instrumental examinations. The blood plasma level of circulating microRNA‑21‑3p was determined by quantitative reverse transcriptase‑polymerase chain reaction (qRT‑PCR) using reagent kits for monitoring and analyzing microRNA expression «TaqMan microRNA Assay» (ThermoFisher Scientific, USA). Small nuclear RNA U6 was used as a reference. Relative expression was calculated in relative units (r.u.) using the ΔΔCt method. Statistical analysis of the obtained data was carried out using standard methods with application packages Microsoft Excel and SPSS 19.0.&#x0D; Results. A significant decrease in the plasma levels of microRNA‑21‑3p in patients with hypertension was established in comparison with practically healthy individuals. The most pronounced decrease in plasma microRNA‑21‑3p levels was observed in patients with the most severe hypertension (stage 3 AH) and in subjects, in whom antihypertensive therapy did not result in the achieving target levels of «office» blood pressure (BP). Significant negative correlations were found between the plasma microRNA‑21‑3p levels and hemodynamic parameters (BP levels) and the left ventricular myocardial mass index — an indicator of the severity of left ventricular hypertrophy, one of the key lesions of target organs. The obtained results indicate the presence in patients with hypertension of a significant deficiency in the production of microRNA‑21‑3p, which, according to the literature data, has pronounced antihypertensive and cardiovascular‑ and renoprotective properties.&#x0D; Conclusions. A significant decrease in the blood plasma levels of microRNA‑21‑3p, the endogenous regulator of gene expression with antihypertensive and organoprotective properties, was established in patients with hypertension in comparison with practically healthy subjects. The revealed decrease in the blood plasma levels of this microRNA was enhanced at severe and uncontrolled hypertension and associated with the degree of hypertensive heart damage. The data obtained indicate the important role of microRNA‑21‑3p in the hypertension pathogenesis and the prospects of finding methods for correcting its production.

Deep learning to detect left ventricular structural abnormalities in chest X-rays.

Early identification of cardiac structural abnormalities indicative of heart failure is crucial to improving patient outcomes. Chest X-rays (CXRs) are routinely conducted on a broad population of patients, presenting an opportunity to build scalable screening tools for structural abnormalities indicative of Stage B or worse heart failure with deep learning methods. In this study, a model was developed to identify severe left ventricular hypertrophy (SLVH) and dilated left ventricle (DLV) using CXRs. A total of 71 589 unique CXRs from 24 689 different patients completed within 1 year of echocardiograms were identified. Labels for SLVH, DLV, and a composite label indicating the presence of either were extracted from echocardiograms. A deep learning model was developed and evaluated using area under the receiver operating characteristic curve (AUROC). Performance was additionally validated on 8003 CXRs from an external site and compared against visual assessment by 15 board-certified radiologists. The model yielded an AUROC of 0.79 (0.76-0.81) for SLVH, 0.80 (0.77-0.84) for DLV, and 0.80 (0.78-0.83) for the composite label, with similar performance on an external data set. The model outperformed all 15 individual radiologists for predicting the composite label and achieved a sensitivity of 71% vs. 66% against the consensus vote across all radiologists at a fixed specificity of 73%. Deep learning analysis of CXRs can accurately detect the presence of certain structural abnormalities and may be useful in early identification of patients with LV hypertrophy and dilation. As a resource to promote further innovation, 71 589 CXRs with adjoining echocardiographic labels have been made publicly available.

Left ventricular hypertrophy: hypertensive or hypertrophic cardiomyopathy? What a dilemma! A case report.

In the presence of the left ventricle hypertrophy (LVH), the differential diagnosis with hypertrophic cardiomyopathy (HCM) or some phenocopy must be always considered, which can be easily suspected when the hypertrophy is markedly asymmetric. However, when the hypertrophy is homogeneous, especially if the patient has concomitant hypertension, it may be a challenge to distinguish between hypertensive and HCM, although some clinical features may help us to suspect it. In addition, patients with HCM may present with exertional angina due to microcirculation involvement in the setting of the hypertrophy itself or dynamic obstruction in the left ventricular outflow tract, but in some cases, the presence of concomitant coronary artery disease must be suspected as the cause of angina, especially if the patient has an intermediate or high-risk probability of having ischemic heart disease. We present the case of a 46-year-old Afro-American man with poorly controlled hypertension who was found to have severe LVH, and who presented with symptoms of exertional angina during follow-up. We will review the clinical features that can help us in the differential diagnosis in this context.

An interventional sheep model of severe aortic valve stenosis hemodynamics for the evaluation of alterations in coronary physiology and microvascular function.

We aimed to develop a large animal model of subcoronary aortic stenosis (AS) to study intracoronary and microcirculatory hemodynamics. A total of three surgical techniques inducing AS were evaluated in 12 sheep. Suturing the leaflets together around a dilator (n = 2) did not result in severe AS. Suturing of a pericardial patch with a variable opening just below the aortic valve (n = 5) created an AS which was poorly tolerated if the aortic valve area (AVA) was too small (0.38-1.02 cm2), but was feasible with an AVA of 1.2 cm2. However, standardization of aortic regurgitation (AR) with this technique is difficult. Therefore, we opted for implantation of an undersized AV-bioprosthesis with narrowing sutures on the leaflets (n = 5). Overall, five sheep survived the immediate postoperative period of which three had severe AS (one patch and two bioprostheses). The surviving sheep with severe AS developed left ventricular hypertrophy and signs of increased filling-pressures. Intracoronary assessment of physiological indices in these AS sheep pointed toward the development of functional microvascular dysfunction, with a significant increase in coronary resting flow and hyperemic coronary resistance, resulting in a significantly higher index of microvascular resistance (IMR) and lower myocardial resistance reserve (MRR). Microscopic analysis showed myocardial hypertrophy and signs of fibrosis without evidence of capillary rarefaction. In a large animal model of AS, microvascular changes are characterized by increased resting coronary flow and hyperemic coronary resistance resulting in increased IMR and decreased MRR. These physiological changes can influence the interpretation of regularly used coronary indices.NEW & NOTEWORTHY In an animal model of aortic valve stenosis (AS), coronary physiological changes are characterized by increased resting coronary flow and hyperemic coronary resistance. These changes can impact coronary indices frequently used to assess concomitant coronary artery disease (CAD). At this point, the best way to assess and treat CAD in AS remains unclear. Our data suggest that fractional flow reserve may underestimate CAD, and nonhyperemic pressure ratios may overestimate CAD severity before aortic valve replacement.

Left ventricular hypertrophy (LVH) in different stages of chronic kidney disease (CKD) patients and its correlation with anaemia

Background : Chronic kidney disease (CKD) is a public health problem that increases the risk of cardiovascular morbidity and mortality. Heart failure with preserved ejection fraction characterized by left ventricular hypertrophy (LVH) and diastolic dysfunction is a common cardiovascular complication of CKD. Anaemia is present in both dialysis &amp; non dialysis CKD patients. Anaemia causes left ventricular hypertrophy (LVH) which in turn leads to increases morbidity and mortality in CKD, even before progression of chronic kidney disease (CKD) to end stage renal disease (ESRD). Our study is aimed at to evaluate the prevalence of left ventricular hypertrophy (LVH) and its correlation with anaemia in hospitalized CKD patients. Materials and Methods : A cross-sectional study was done on 50 patients of different stages of CKD admitted in the chittagong medical college hospital (CMCH). All the clinical data were reviewed and recorded. Data was analyzed by SPSS-18 and p value &lt;0.05 was considered statistically significant. Results : Majority of study population 64% was male, 36% was female. Most of the male patient (40%) of the study population were having abnormal left ventricular mass index (&gt;130 gm/m2). More patients with severe left ventricular hypertrophy were found in stage 5 of CKD in female and male which was 8 and 23 respectively. Regarding correlation of Hb% with LVMI there was a significant negative correlation was found (r= -0.420, p = 0.003) between them means if Hb% decreases LVMI level increases. It was also found in male and female patients separately ( for male r = -0.778, p = 0.001 and for female r = -0.746, p = 0.001). Conclusion : Anemia is widely prevalent in our CKD patients. Severity of anemia is correlated to left ventricular hypertrophy in these patients. Hence correction of anemia early in these group of patients can halt or prevent cardiovascular morbidity and mortality. J Bangladesh Coll Phys Surg 2024; 42: 25-30

Cholecalciferol, serum calcium and left ventricular hypertrophy in essential hypertension.

Objective: To assess the correlation of vitamin cholecalciferol and serum calcium with left ventricular hypertrophy (LVH) in essential hypertension patients presenting at a tertiary care hospital. Study Design: Cross Sectional Comparative study. Setting: Department of Cardiology and Medicine, Liaquat University of Medical and Health Sciences, Jamshoro, Sindh. Period: July 2019 to January 2021. Material &amp; Methods: 100 diagnosed LVH+ Essential Hypertenison cases and 100 diagnosed essential hypertension (controls) were selected through non- probability purposive sampling. Echocardiography, serum cholecalciferol, calcium, phosphate, parathyroid hormone (PTH), alkaline phosphatase (ALP), urea and creatinine were measured form sera. Devereux’s formula measured the LV thickness LVH. SPSS ver. 21.0 analyzed the descriptive statistics and compared the variables at 95% Confidence interval (P≤0.05). Results: Serum calcium, phosphate and parathyroid hormone were found elevated in LVH cases compared to control (P=0.0001). Cholecalciferol in LVH cases was low noted as 27.3±7.84 ng/dl compared to 39.5±0.43 ng/dl in controls (P=0.0001). Cholecalciferol in mild, moderate and severe LVH cases was descending order as 30.67±7.84, 24.76±7.72 and 14.96±6.12 mm respectively (P-0.0001). Serum cholecalciferol proves inverse association (r= -0.180) with LVH (p=0.003). Conclusion: The present study reports vitamin cholecalciferol deficiency increases the chances of left ventricular hypertrophy through increased secretion of parathyroid hormone that induces de – novo protein synthesis of ventricular myocardium.

Modeling the Relationship Between Diastolic Phenotype and Outcomes in Pediatric Hypertrophic Cardiomyopathy

Pediatric hypertrophic cardiomyopathy (HCM) is associated with adverse events. The contribution of diastolic dysfunction to adverse events is poorly understood. The aim of this study was to explore the association between diastolic phenotype and outcomes in pediatric patients with HCM. Children <18years of age with diagnosed with HCM were included. Diastolic function parameters were measured from the first echocardiogram at the time of diagnosis, including Doppler flow velocities, tissue Doppler velocities, and left atrial volume and function. Using principal-component analysis, key features in echocardiographic parameters were identified. The principal components were regressed to freedom from major adverse cardiac events (MACE), defined as implantable cardioverter-defibrillator insertion, myectomy, aborted sudden cardiac death, transplantation, need for mechanical circulatory support, and death. Variables that estimate left ventricular filling pressures were highly collinear and associated with MACE (hazard ratio, 0.86; 95% CI, 0.75-1.00), though this was no longer significant after controlling for left ventricular thickness and genetic variation. Left atrial size parameters adjusted for body surface area were independently associated with outcomes in the covariate-adjusted model (hazard ratio, 0.69; 95% CI, 0.5-0.94). The covariate-adjusted model had an Akaike information criterion of 213, an adjusted R2 value of 0.78, and a concordance index of 0.82 for association with MACE. Echocardiographic parameters of diastolic dysfunction were associated with MACE in this population study, in combination with the severity of left ventricular hypertrophy and genetic variation. Left atrial size parameters adjusted for body surface area were independently associated with adverse events. Additional study of diastolic function parameters adjusted for patient size could facilitate the prediction of adverse events in pediatric patients with HCM.

GI Amyloid: More Than a Heavy Heart

Amyloid transthyretin (ATTR) amyloidosis is caused by the accumulation of insoluble transthyretin (TTR) amyloid fibrils. These proteins can build up in various organ systems such as the musculoskeletal, gastrointestinal, and ocular system. However, there is usually a predilection for the heart and nervous system [1]. ATTR comprises approximately 16% of GI amyloid cases, with the small bowel being the most common area of involvement [2]. Symptoms typically include abdominal pain, nausea and vomiting, unintentional weight loss, diarrhea, and constipation. Given the rarity of the disease, we present a case of biopsy proven ATTR GI amyloidosis to raise awareness and, consequently, aid in early recognition. Our patient is a 48-year-old female with a medical history of substance use disorder who had multiple evaluations for complaints of chest discomfort and gastrointestinal symptoms including nausea, vomiting and diarrhea. Initial evaluation included an echocardiography which found severe left ventricular hypertrophy. Given her significant family history of myocardial infarction, a left cardiac catheterization was completed, however, this revealed normal coronary vasculature. Subsequently, the patient started medical therapy for heart failure with preserved ventricular function pending further testing. Despite medical management, the patient developed worsening symptoms of heart failure warranting repeat echocardiography which showed a significant reduction in ejection fraction. In addition to the patient's worsening cardiac symptoms, she continued to have refractory gastrointestinal symptoms and developed new epigastric pain. Therefore, the patient underwent upper endoscopy with discovery of abnormal peristalsis. After which, a gastric emptying study was done, resulting in a diagnosis of gastroparesis. With the constellation of findings i.e., the pattern of ventricular hypertrophy, lack of hypertensive and coronary artery disease, as well as gastroparesis without a known etiology, there was suspicion for systemic infiltrative disease, which led to further investigation. Gastric, small, and large bowel biopsies confirmed amyloid deposits. The patient also underwent a Tc99m-PYP scan which revealed evidence of cardiac amyloidosis; monoclonal protein analysis test was negative, and a cardiac biopsy showed a profile consistent with amyloid transthyretin type. The patient remained on pharmacologic therapy for gastroparesis and has been referred to cardiac transplantation services for further management.Our case highlights that amyloidosis, including GI amyloidosis, has the potential to go unrecognized due to non-specific signs and symptoms. Clinicians should therefore always have a high index of suspicion as GI involvement in systemic amyloidosis, regardless of protein subtype, is common. This high index of suspicion will allow for the appropriate pathologic examination to be pursued, and ultimately the appropriate management.

Sex differences in aortic stenosis progression and myocardial response

Abstract Background Aortic stenosis (AS) produces an increased afterload and consequently left ventricular (LV) remodeling. While current guidelines recommend the same echo-doppler criteria for diagnosis and grading of AS for men and women, different sex-specific patterns of cardiac remodeling, and eventually damage, have been reported. Whether these different patterns are caused by sex-related AS progression rate or myocardial response is less well known. Aim We aim to compare longitudinal changes in aortic valve and cardiac function between women and men with AS to investigate sex-related differences in AS progression and cardiac remodeling. Methods Patients with mild-to-severe AS and LV ejection fraction (LVEF) ≥ 50 % at least in 2 transthoracic echocardiograms (TTE) were retrospectively identified. Prosthetic and bicuspid valves were excluded. Serial TTEs provided a multiparametric framework to compare AS severity, progression rate and induced cardiac changes between sexes. Results 914 patients were included (median follow-up time of 6.8 years) and 52 % (473) were female. Both sexes had similar baseline aortic peak velocities (APV) (2.9±0.9 m/s), mean pressure gradient (MPG) (27±13 mmHg) and LVEF (60±5 %). Women were older (75±9 vs 73±8 years; p&amp;lt;0.001), had smaller body surface area (BSA) (1.70±0.15 vs 1.88±0.16 m2, p&amp;lt;0.001), proportionally lower stroke volume (SV) (82±19 mL vs 91±22 mL, p&amp;lt;0.001), lower indexed LV mass (iLVM) (118±33 g/m2 vs 125±28 g/m2, p&amp;lt;0.001) and higher indexed left atrial (LA) volume (39±13 vs 49±20 mL/m2, p&amp;lt;0.001). The average annual progression rate of APV and MPG was similar for both groups (2 mmHg/year and 0.14 m s-1 year-1). After multivariate adjustment including time-dependent aortic valve replacement, women had a higher incidence of severe LV hypertrophy as measured by iLVM (HR=1.16, CI=1.08-1.91, p&amp;lt;0.01), moderate-to-severe tricuspid valve regurgitation (HR=2.03, CI=1.01-4.07, p&amp;lt;0.05) and pulmonary hypertension (PHT) (HR=1.49, CI=1.02-2.18, p=0.04) at 5 years. Similar incidence rates were seen for LV dilation, LVEF reduction and mitral valve regurgitation. All-cause mortality rates were similar between groups (p=0.30). Conclusion This study suggests that under similar static and dynamic loading conditions, women will develop severe LV hypertrophy and PHT earlier than men, possibly reflecting sex-specific response differences intrinsic to the myocardium. This suggests that the definition of AS severity may benefit from a shift from a valve-focused to a myocardial-integrative approach taking gender into account.

Electrocardiographic evolution in Anderson-Fabry disease: a valuable tool to detect progressive cardiac involvement

Abstract Background Anderson-Fabry disease (AFD) is a multisystemic disorder caused by accumulation of glycosphingolipid in affected tissues and cardiac involvement can manifest with left ventricular hypertrophy (LVH), conduction delays, arrythmias and valvulopathies. Electrocardiogram (ECG) has proven to be useful for early detection of this condition, but there are only few datas on the association between ECG alterations and the progression of the disease. Purpose To evaluate the association between ECG anomalies and progressive cardiac involvement in AFD patients with different degrees of left ventricular hypertrophy. Methods We recruited 189 AFD patients &amp;gt; 18 years old (39% males, median age 47 years, 68% classical AFD) in a multicentre cohort and we divided them into 4 groups according to different degree of left ventricular (LV) thickness: group A ≤ 9mm (n = 52, 28%); group B 10-14 mm (n = 76, 40%); group C 15-19 mm (n = 46, 24%); group D ≥ 20 mm (n = 15, 8%). They underwent a complete clinical, ECG and echocardiographic evaluation and we analysed their ECG features in order to detect patterns suggestive of the different stages of AFD. Results A normal ECG was present in 87% of patients in group A, 54% in group B, 11% in group C, and 7% in group D. The most common conduction delay type was right bundle branch block (RBBB), mainly incomplete in groups B and C (respectively 20% and 22%) and complete RBBB in group D (53%), with p &amp;lt; 0.001; whereas none of the patients had LBBB. The prevalence of LVH criteria showed a statistically significant increase among the groups (p &amp;lt; 0.001) and also negative T waves and ST segment depression were more frequent in group C and D (p &amp;lt; 0.001), involving mainly lateral and inferior leads. Analysing these results we proposed ECG patterns representative of different AFD stages characterized by increasing LV thickness. In patients with normal LV thickness (group A) we noticed a high prevalence of normal ECG (87%) and minor anomalies like LVH criteria/giant positive T waves (8%) and delta wave/slurred QRS onset together with borderline PR (8%). Differently patients with intermediate LV thickness (group B and C) show more heterogeneous ECG alterations: LVH/giant positive T waves (17% and 7%); LVH+LV strain (9% and 17%); incomplete RBBB associated with repolarization abnormalities (8% and 9%) which were more frequently associated with LVH criteria in group C than B (8% and 15% respectively). In patients with severe LVH (group D) we detected more significant anomalies, like complete RBBB associated to LVH and repolarization abnormalities (40%), sometimes with QRS fragmentation (13%). Conclusions ECG represents an important tool for early detection and long-term monitoring of cardiac involvement in AFD with particular ECG features that evolve together with the natural history of the disease and with the progression of the LVH. Their potential association with clinical events remains unknown.

Abstract 11700: Left Ventricular Global Longitudinal Strain After Transcatheter Aortic Valve Implantation in Patients With Preserved Ejection Fraction

Background: Left ventricular (LV) global longitudinal strain (GLS), which could assess subtle LV dysfunction, is already deteriorated in a certain number of aortic stenosis (AS) patients with preserved ejection fraction (EF). Although GLS improves after valve replacement, detailed outcome is not well understood. Research Question: In AS patients with preserved EF undergoing transcatheter aortic valve implantation (TAVI), is there a difference in post-procedural GLS between patients with and without reduced pre-procedural GLS? Aim: To elucidate the post-procedural course of GLS after TAVI. Methods: The present study was a single-center retrospective cohort study that included 119 out of 347 consecutive patients undergoing TAVI by excluding EF &lt;50%, atrial fibrillation, inadequate echo image for analysis, and loss to follow-up echocardiography. Subjects were divided into two groups according to pre-procedural GLS: reduced GLS (r-GLS) (&gt; -15%) and preserved GLS (p-GLS) (≤ -15%), and echocardiographic parameters at baseline and changes from baseline to mid-term follow-up (6 months to 1 year) were compared. Results: There was no significant difference in baseline characteristics ( Table ). Before the procedure, higher severity of AS, higher LV mass index and E/e’, and lower EF and peak left atrial longitudinal strain were observed in r-GLS. Both EF and LV mass index improved after TAVI in r-GLS and became comparable in p-GLS ( Figure ). After TAVI, GLS improved in r-GLS, but remained significantly inferior to p-GLS (-14.7 ± 2.3% vs. -16.5 ± 2.8%, P &lt; 0.001; Figure ). Conclusions: In AS patients with preserved EF, GLS improved after TAVI in patients with r-GLS but remained inferior to those with p-GLS, suggesting underlying refractory myocardial damage presumably caused by more severe AS and consequently more severe LV hypertrophy in patients with r-GLS. It might indicate the possibility of GLS for determining optimal timing of TAVI in AS patients with preserved EF.

Abstract 17085: An Unusual Case of Severe Hypertrophic Cardiomyopathy in a 23-Year-Old Systemic Lupus Erythematosus Patient on Hydroxychloroquine

A 23-year-old female with Systemic lupus erythematosus (SLE), lupus nephritis, antiphospholipid syndrome, venous thromboembolism, stroke, Libman-Sacks endocarditis, and hypertension presented with right upper and lower extremity weakness, right facial droop, and aphasia. Her home medications included hydroxychloroquine, mycophenolate, apixaban, and losartan. ECG showed normal sinus rhythm, left atrial enlargement, ST and T wave abnormalities in V5 and V6. Computed tomography angiography of the brain showed left middle cerebral artery occlusion. Transthoracic echocardiogram (TTE) showed left ventricular ejection fraction of 65%, severe left ventricular hypertrophy, moderate pericardial effusion, and moderately thickened mitral valve (MV) leaflets. Transesophageal echocardiogram showed large vegetations on atrial aspect of both MV leaflets concerning for Libman-Sacks endocarditis. We attempt to investigate the cause of this hypertrophic cardiomyopathy (HCM) in a young patient with SLE. Few reported cases of HCM in patients with SLE were medication induced. Tacrolimus has been observed to induced HCM in a Japanese patient with dermatomyositis. Hydroxychloroquine has been associated with myocardial thickening. Its use can lead to enlarged myocardiocytes with intracytoplasmic vacuoles consisting of concentric lamellar myelin figures in single membrane bound vesicles, curvilinear bodies, glycogen accumulation and fused mitochondria. Hydroxychloroquine use led to reversible inhibition of lysosomal enzyme activity. Cessation of medication use in both cases led to reduction in left ventricle thickness. These patients, like our own, has no family history of aortic valve stenosis, mitral valve prolapse, or HCM. However, this patient’s use of hydroxychloroquine to treat her SLE can be assumed to be a contributing factor to her HCM. This could suggest possible screening with ECG and TTE in patients taking hydroxychloroquine.

Abstract 17496: Exploring the Benefits: Role of Repeat Transesophageal Echocardiography (TEE) in Patients Anticoagulated for Four Weeks

Background: A left atrial appendage (LAA) thrombus is a well-known complication of atrial fibrillation (AF). Vitamin K antagonists (VKAs) have been well studied been considered the gold standard for thromboembolic prophylaxis. We present a case of LAA thrombus despite compliance with VKAs. Clinical presentation: A 70-year-old female with atrial fibrillation and diabetes presented with left-sided weakness and left facial droop, CT head showed right middle cerebral artery infarct. Vitals were unremarkable. Electrocardiogram showed AF with a rapid ventricular response. She was on warfarin with the most recent international normalized ratio level of 2.3. Transthoracic echocardiography revealed an ejection fraction of 55%, severe left ventricular hypertrophy, and severely dilated left atrium (LA) with LA diameter of 5.3 cm (&gt;= 4.7 cm in women indicates severe dilatation). Transesophageal echocardiography (TEE) with bubble study demonstrated a large thrombus in the LAA with evidence of patent foramen ovale. The pulse wave Doppler (PWD) of the LAA on TEE also showed an LAA velocity of &lt;20 cm/sec, which indicated that there was the highest probability that the thrombus was forming within LAA. Hypercoagulability work-up for thrombosis while on Coumadin such as anti-B2 glycoprotein, anticardiolipin, and factor V Leiden mutation were negative. The patient was started on enoxaparin with appropriate follow-up upon discharge. Discussion: The prevalence of LAA thrombus in patients with AF receiving a minimum of 3 weeks of anticoagulation, was approximately 3%. The presence of a LAA thrombus is a known contraindication to cardioversion and catheter ablation in patients with AF as it can result in cardioembolic stroke. However, current guidelines for cardioversion do not recommend pre-procedural TEE in patients undergoing cardioversion for AF if they have been on therapeutic oral anticoagulation for at least 3 weeks while TEE use remains variable before catheter ablation.

Abstract 12381: De Novo Multiple Myeloma in a Patient With Transthyretin Amyloid Cardiomyopathy

Background: The development of de novo multiple myeloma in a patient with transthyretin amyloid cardiomyopathy (ATTR-CM) is rare and is often associated with poor prognosis. Early and definitive diagnosis is crucial to improve survival. Case: A 63-year-old male was evaluated for heart failure. He had a history of hypertension, sick sinus syndrome status post dual chamber pacemaker, non-sustained ventricular tachycardia requiring ablation in addition to bilateral carpal tunnel syndrome, spontaneous biceps tendon rupture, and lumbar spinal stenosis. Transthoracic echocardiogram showed progressive severe left ventricular hypertrophy with a septal thickness of 2.0cm with a normal left ventricular ejection fraction. Decision-Making: Given his history, an amyloid evaluation was performed. Serum and urine assessment for light chain amyloidosis revealed elevated kappa free light chains with kappa/lambda free light chain ratio of 19.30. Bone marrow biopsy at that time showed normocellular bone marrow with less than 3% plasma cells. An abdominal fat pad biopsy was inconclusive. A cardiac MRI was unobtainable given non-compatible pacemaker leads and a technetium-99m pyrophosphate scintigraphy was deferred given his abnormal light chains. An endomyocardial biopsy was performed and revealed wild-type ATTR deposition by mass spectrometry. Serum genetic test confirmed the absence of TTR gene mutation. The patient was started on Tafamadis. Six months later, he was noted to have progressive elevation in kappa free light chains on serial evaluation and underwent a repeat bone marrow biopsy. This showed plasma cell myeloma with 25-30% marrow cellularity and flow cytometry consistent with kappa light chain multiple myeloma. He was started on Daratumumab, Lenalidomide, and Dexamethasone. This resulted in normalization of his free light chain ratio and morphologic remission on repeat bone marrow biopsy. Conclusion: In patients who are found to have monoclonal gammopathy, an endomyocardial biopsy is crucial to evaluate for amyloid cardiomyopathy. These patients should also be monitored for the progression to multiple myeloma.

Abstract 18713: The Impact of ECG-AI Design Choices on Clinical Utility: A Deep Dive Into Left Ventricular Hypertrophy, Hypertrophic Cardiomyopathy, and Cardiac Amyloidosis

Introduction: Artificial intelligence applied to electrocardiograms (ECG-AI) enables early and efficient detection of cardiovascular disease. The technical and clinical impact of different approaches to designing ECG-AI remains under-explored. We consider left ventricular hypertrophy (LVH) and examine the impact of disease-specific labeling of minority etiologies of left ventricular wall thickening- hypertrophic cardiomyopathy (HCM) and cardiac amyloidosis (CA) - on ECG-AI performance. Hypothesis: ECG-AI designed to detect HCM or CA outperforms ECG-AI broadly trained to identify LVH due to differences in attention to key ECG features associated with HCM or CA. Methods: Independent neural networks were trained to identify HCM, CA, and LVH. HCM and CA patients were identified using the full depth of EHR data and validated via clinician adjudication (N = 3,025 and 4,251 patients, respectively). Moderate and severe LVH patients (N = 98,144) were identified using echocardiogram results and international LVH criteria. We compared the ability of disease-specific ECG-AI vs. LVH ECG-AI to detect HCM (or CA) by examining model performance within each of the three test sets. Results: 52.6% of HCM patients and 49.5% of CA patients met LVH criteria. Within the HCM test set, the AUROC, sensitivity, specificity, and positive predictive value (PPV) of the HCM ECG-AI were 0.94, 0.88, 0.85, and 60%, respectively, whereas the same for LVH ECG-AI were 0.83, 0.83, 0.64, and 37%. Within the CA test set, CA ECG-AI achieved AUROC, sensitivity, specificity, and PPV of 0.94, 0.81, 0.91, and 69%, respectively, whereas the same for LVH ECG-AI were 0.75, 0.73, 0.68, and 31%. ECGs positive for HCM exhibited higher P wave area, QRS deflection and R wave amplitude compared to LVH-positive ECGs (Cohen's D &gt; 0.75). ECGs positive for CA exhibited lower R wave amplitude/area, QRS deflection and QRS areas (Cohen's D &gt; 0.6). Conclusion: Models trained using carefully labeled HCM or CA identify distinct signals associated with the diseases, resulting in improved disease discrimination compared to a model trained to identify echocardiographic left ventricular thickening. Labeling choices should be communicated transparently to clinicians to ensure safe and effective use of ECG-AI.

Evolving Concept of Aortic Valve Replacement in Asymptomatic Patients With Severe Aortic Stenosis

BackgroundSurgical treatment of asymptomatic severe aortic stenosis (AS) has been gaining attention ever since the results of the Early Surgery Versus Conventional Treatment in Very Severe Aortic Stenosis (RECOVERY) and Aortic Valve replacement versus conservative treatment in Asymptomatic seveRe aortic stenosis (AVATAR) trials showed survival benefits with early surgical aortic valve replacement (SAVR). This study analyzed the long-term clinical and echocardiographic outcomes of SAVR in asymptomatic severe AS. MethodsBetween 2002 and 2020, 272 patients with asymptomatic severe AS and a left ventricular ejection fraction ≥50% underwent SAVR with or without concomitant aortic surgery and met the study criteria. The median follow-up was 8.5 years (interquartile range, 6-12.8 years), for a total of 2584 patient-years. The time course of the left ventricular mass index (LVMI) and the average E/E′ (ratio of the Doppler-derived E wave to the tissue Doppler-derived E′ wave) were assessed using 594 postoperative echocardiograms. The association of preoperative LVMI and average E/E′ with survival was assessed using Cox proportional hazards. ResultsThere was no operative mortality. On longitudinal analyses, LVMI improved in patients who presented with moderate or severe preoperative left ventricular hypertrophy (LVH). However, after the early decline in average E/E′, there was a late increase to greater than upper limit normal, particularly in patients with a preoperative average E/E′≥14. Postoperative survival was 100%, 94%, 84%, and 76% at 1, 5, 10, and 15 years, respectively, comparable to age- and sex-matched expected survival on the basis of the US general population. On adjusted Cox survival analysis, only moderate to severe LVH was associated with a survival penalty (hazard ratio], 2.32; 95% CI, 1.02-5.27; P = .045). ConclusionsIn asymptomatic patients with AS, SAVR restores survival and improves LVH, but patients with diastolic dysfunction are left with persistent dysfunction. Presentation with moderate or severe LVH at the time of surgery translated to a survival penalty. This observational study supports early SAVR in this population before development of LVH, although further investigation is needed.