Left Ventricular Wall Thickness Research Articles

Advances in Cardiac Imaging and Genetic Testing for Diagnosis and Risk Stratification in Cardiomyopathies: 2024 Update

Cardiomyopathies represent a diverse group of heart muscle diseases marked by structural and functional abnormalities that are not primarily caused by coronary artery disease. Recent advances in non-invasive imaging techniques, such as echocardiography, cardiac magnetic resonance, and computed tomography, have transformed diagnostic accuracy and risk stratification, reemphasizing the role of cardiac imaging in diagnosis, phenotyping, and management of these conditions. Genetic testing complements imaging by clarifying inheritance patterns, assessing sudden cardiac death risk, and informing therapeutic choices. Integrating imaging data, such as left ventricular wall thickness, fibrosis, and apical aneurysms, with genetic findings enhances decision-making for implantable cardioverter-defibrillators in high-risk patients. Emerging technologies like artificial intelligence, strain imaging, and molecular imaging, alongside genetic testing, hold the promise of further refining diagnosis and personalized treatment approaches. This article summarizes the current state and future perspectives of cardiac imaging and genetic testing for diagnosis and risk stratification in cardiomyopathies, offering practical insights for patients’ management.

Long-term clinical outcomes after alcohol septal ablation for hypertrophic obstructive cardiomyopathy in Japan: a retrospective study.

Hypertrophic cardiomyopathy is characterized by significant left ventricular wall thickening, often leading to obstructive symptoms. Alcohol septal ablation (ASA) has emerged as an effective treatment for patients with hypertrophic obstructive cardiomyopathy (HOCM) who remain symptomatic despite maximal medical therapy. However, the detailed long-term effects of ASA in Japanese patients with HOCM remain unclear. Therefore, this study aimed to investigate the long-term effects of ASA for HOCM by evaluating changes in symptoms, pressure gradient, hemodynamics, prognosis, and predictive factors for cardiovascular events over time. In this retrospective study, we examined 239 highly symptomatic patients (age, 64 ± 13years; median follow-up, 6.9years) treated with ASA for drug-refractory HOCM between 1998 and 2021. Patients were assessed using transthoracic echocardiography, magnetic resonance imaging, and cardiac catheterization. Follow-up evaluations included clinical assessments, electrocardiography, and echocardiography. Data analysis included descriptive statistics, Kaplan-Meier analysis, and multivariate regression. ASA reduced the left ventricular outflow tract gradient from 90.5 ± 52.8 to 14.4 ± 17.1mmHg (P < 0.01) and New York Heart Association (NYHA) class from 3 [2.5-3] to 1 [1-2] at 10years after ASA (P < 0.01). The 30-day mortality rate following ASA was 1%. Overall, 31 patients (13%) died during the follow-up period. The survival rates at 1, 5, 10, and 15years after ASA were 97.4%, 89.9%, 83.7%, and 77.6%, respectively. Multivariable analysis revealed NYHA functional class before ASA (odds ratio [OR], 3.09; 95% confidence interval [CI], 1.40-6.82; P = 0.005), beta-blocker use (OR, 0.25; 95% CI, 0.07-0.91; P = 0.036), and class Ia agent use (OR, 0.31; 95% CI, 0.13-0.75; P = 0.009) as independent predictors of all-cause mortality. This study demonstrated low periprocedural and long-term mortality rates following ASA in patients with HOCM, suggesting that ASA provides durable symptomatic relief and reduces left ventricular outflow tract obstruction in selected highly symptomatic patients with HOCM.

The prevalence of murmurs and gallop sounds in anemic cats.

There is little information on the prevalence of auscultatory abnormalities in anemic cats. This study aimed to describe the prevalence of cardiac murmurs and gallop sounds in a population of anemic and nonanemic cats presenting to an emergency room (ER) and to assess whether the prevalence of auscultatory abnormalities was influenced by the severity of anemia. Records of cats presenting to an ER between May 2021 and May 2022 or receiving a blood transfusion between September 2019 and January 2022 were retrospectively analyzed for presence of a murmur or gallop sound. Cats with known structural heart disease were excluded. A murmur was found in 56 of 185 (30%) anemic cats compared with 11 of 102 (11%) nonanemic cats (p<0.001), with a higher proportion in cats with PCV <16% (p<0.001). Twenty-five of 185 (14%) anemic cats had a gallop compared with 4 of 102 (4%) nonanemic cats (p=0.009), with the highest proportion in cats with PCV 11%-20% (p<0.001). Echocardiography was performed on 17 of 185 anemic cats; 8 had normal echocardiograms and 9 demonstrated evidence of chamber dilation without left ventricular wall thickening, consistent with anemia. Abnormalities on auscultation are common in anemic cats presenting to the ER, with a higher prevalence in more severely anemic cats.

Abstract 4120573: Abrupt cardiac rupture of the patient with ATTR amyloidosis

A Japanese male in his 80s was admitted to our emergency department with chest pain. His prior history was syncope and ventricular tachycardia. Transthoracic echocardiography (TTE) revealed thickening of the basal part of the antero-septal wall and thinning of the basal part of the inferior wall. Coronary angiography (CAG), cardiac MRI and blood test revealed no specific abnormalities. The day before his emergency admission, he visited the cardiology outpatient department for a periodic examination of cardiac hypertrophy. ECG, chest X-ray, and TTE were unchanged from his prior examination. However, that night, he experienced chest pain and was transferred to our hospital. On arrival, his vital signs were critical, with a blood pressure of 70/59 mmHg. ECG indicated ST elevation in antero-lateral leads. TTE detected pericardial effusion, and contrast-enhanced CT identified two focal areas of non-enhancement in the myocardium and pericardial effusion without signs of aortic dissection. CAG revealed no significant stenosis or obstructive lesion. During coronary angiography, the patient deteriorated to asystole. Cardiopulmonary resuscitation and percutaneous pericardial drainage were initiated. Hemorrhagic pericardial effusion was aspirated. Immediate surgical hemostasis was undergone, revealing about 2 cm lacerations and hematoma in the anterior and inferior wall. After surgery, he complained of abdominal discomfort. Esophageal gastrointestinal endoscopy was undergone to investigate the abdominal discomfort, and he was diagnosed with early gastric cancer. Endoscopic submucosal dissection (ESD) was undergone, and histopathological examination revealed adenocarcinoma and eosinophilic amorphous materials deposited in the submucosal vessels. Congo red staining of the submucosal vessels revealed orange-red areas. A technetium-99m pyrophosphatase scintigraphy showed Grade 2 uptake in the heart. Transthyretin (TTR) staining was positive in the specimen from ESD, leading to a diagnosis of TTR amyloidosis. Genetic test for TTR was negative, which led to a diagnosis of wild-type TTR amyloidosis and tafamidis was started. In cases of acute pericardial effusion and/or cardiac rupture, it is imperative to consider cardiac amyloidosis as a potential etiology, in addition to myocardial infarction and aortic dissection, especially in patients with left ventricular wall thickening, neuropathy, or abnormal ECG, also known as “red flag”.

Abstract 4136016: Higher aircraft noise exposure associates with worse heart structure and function

Introduction: Aircraft noise is a concern for communities living near airports, but its impact on heart structure and function is unknown. Methods: Night-time (L night ) and weighted 24-hour day (L den ) aircraft noise levels were provided by the UK Civil Aviation Authority for 2011 (Fig.1). Health data came from UK Biobank (UKB) participants living near four UK major airports (Heathrow, Gatwick, Manchester, and Birmingham) who had cardiovascular magnetic resonance (CMR) imaging starting from 2014 and self-reported no hearing difficulties. Generalized linear models investigated the associations between aircraft noise exposure and CMR metrics (derived using a validated convolutional neural network to ensure consistent image segmentations), after adjustment for demographics, socio-economic, lifestyle, and environmental covariates. Mediation by cardiovascular (CV) risk factors was also explored. Downstream associations between CMR metrics and major adverse cardiac events (MACE) were tested in a separate prospective UKB subcohort (n=26,658) to understand the potential clinical impact of noise-associated heart remodeling. Results: Of 3,635 UKB participants included, 3% experienced higher aircraft noise L night (≥45decibels) and 8% higher L den (≥50decibels). Participants exposed to higher L night had 7% [95% confidence interval: 4–10%] higher left ventricular (LV) mass and 4% [2–5%] thicker LV walls with a normal septal:lateral wall thickness ratio (Fig.2 A1). This LV concentric remodeling is relevant since 7% higher LV mass associates with 32% higher odds of MACE. They also had worse LV myocardial dynamics (Fig.2 A2) (e.g., 8% [4–12%] lower global circumferential strain which associates with 37% higher odds of MACE). Overall, a hypothetical individual experiencing the typical CMR abnormalities associated with higher L night exposure may have 5-times higher odds of MACE. Body mass index and hypertension appeared to mediate 20-50% of the observed associations. Findings were similar in those exposed to higher L den (Fig.2 B1-2). Participants who did not move home during follow-up and were continuously exposed to higher aircraft noise levels had the worst CMR phenotype. Conclusion: Higher aircraft noise exposure associates with adverse LV remodeling, potentially due to noise increasing the risk of obesity and hypertension. Findings are consistent with the existing literature on aircraft noise and CV disease, and need to be considered by policymakers and the aviation industry.

Abstract 4135476: The Cardiomyocyte Hypertrophy Inhibitor RFN-409, Identified by High Throughput Screening Assay, Suppresses Pressure Overload-induced Systolic Dysfunction in Mice by Suppressing p38 Activity

Purpose: When the heart is exposed to stresses such as myocardial infarction or hypertension, it undergoes compensatory hypertrophy in response. However, continuation of the stress causes this compensatory mechanism to fail, and eventually systolic dysfunction or decompensated heart failure occur. As the hypertrophy of individual cardiomyocytes has been observed in this process, controlling cardiomyocyte hypertrophy is a potential target the prevention and treatment of heart failure. In this study, we constructed a high throughput screening (HTS) assay using cardiomyocyte hypertrophy as an index parameter. Compounds that inhibit cardiomyocyte hypertrophy were selected from our low molecular compound library. Methods and Results: In the primary screening, cultured rat primary cardiomyocytes were treated with each compound at a final concentration of 1 µM and then stimulated with 30 µM phenylephrine (PE) for 48 hours. These cells were subjected to fluorescent immunostaining with α-actinin, and cardiomyocyte area was measured using an ArrayScan™ system. The hypertrophy inhibition rate (%) of each compound was calculated as [(PE(+) - compound) / (PE(+) - PE(-))] × 100. The compounds with a hypertrophy inhibition rate greater than 50% and less than 150% were selected as hit compounds. In the secondary screening, these hit compounds were evaluated based on the dose-dependency of cardiomyocyte hypertrophy inhibition and the inhibition of the mRNA levels of the cardiac hypertrophy response genes ANF and BNP using real-time PCR. From the 269 low molecular-weight compounds in the original compound library, eight were selected through the primary and secondary screenings. Among them, we focused on Reference Number 409 (RFN-409). Western blotting indicated that RFN-409 inhibited PE-induced p38 activation. Next, we investigated the effect of RFN-409 on heart failure. Eight-week-old male C57 BL/6J mice were subjected to transverse aortic constriction (TAC) surgery and then randomly assigned to intraperitoneal treatment with RFN-409 (3, 10 mg/kg) or vehicle for eight weeks. RFN-409 at 10 mg/kg significantly prevented TAC-induced increase in left ventricular posterior wall thickness and decrease in left ventricular fractional shortening. Discussion: RFN-409 suppressed TAC-induced development of heart failure, at least partially by inhibiting p38 activity. These findings suggest that RFN-409 may be an effective agent for heart failure therapy.

Abstract 4137339: Application of PLGA-PEG-PLGA Thermosensitive Hydrogel Loaded with Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes and Ginsenoside Rb3 in the Treatment of Acute Myocardial Infarction

Background: Ginsenoside Rb3 (GSRb3) is a traditional Chinese medicine monomer. We aim to investigate the effects of GSRb3 on the proliferation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and the reparative effects of PLGA-PEG-PLGA thermosensitive hydrogel loaded with hiPSC-CMs and GSRb3 (NP GSRb3 @Gel+iCM) on myocardial infarction (MI). Methods: 1. Western Blot, RT-qPCR, cell immunofluorescence staining, and CCK-8 assays were employed to assess the proliferative effects of different concentrations of GSRb3 on neonatal mouse primary cardiomyocytes (NCMs) and hiPSC-CMs. 2. Transcriptomic gene sequencing technology was utilized to investigate the mRNA expression changes of hiPSC-CMs induced by GSRb3; The NP GSRb3 @Gel+iCM was injected into the left ventricular myocardium of the MI mice; the same volume injections of hiPSC-CMs (iCM group) and PLGA-PEG-PLGA thermosensitive hydrogel loaded with GSRb3 (NP GSRb3 @Gel group) served as control; Additionally, MI model group without additional treatment and sham group were established. 3. At 4 weeks post-MI, echocardiography, Sirius Red/Fast Green staining and immunofluorescence staining were utilized to evaluate the heart function, infarction size and survival rate of transplanted hiPSC-CMs. Results: GSRb3 inhibit the apoptosis of NCMs while promote proliferation of NCMs and hiPSC-CMs significantly. After 4 weeks of treatment, the engraftment rate of hiPSC-CMs in NP GSRb3 @Gel+iCM group (36.7%) was 4.8 times that of iCM group (7.7%); Compared to the MI group, NP GSRb3 @Gel group and iCM group, NP GSRb3 @Gel+iCM group showed significant improvement in cardiac function; The myocardial repair effect in NP GSRb3 @Gel+iCM group was significantly superior to NP GSRb3 @Gel group and iCM group, with a 47% reduction in infarct size compared to MI group, and further reduction in left ventricular anterior wall thickness compared to NP GSRb3 @Gel group and iCM group. Conclusion: GSRb3 promotes the proliferation of hiPSC-CMs both in vitro and in vivo. NP GSRb3 @Gel+iCM significantly increase the engraftment of hiPSC-CMs, promote angiogenesis, reduce infarction size, inhibit left ventricular remodeling and improve cardiac function.

Abstract 4138380: Cardiac protection of hiPSC-CMs loaded chitosan cardiac patch in myocardial infarcted swine

Background: The low grafting rate of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) following direct injection into the myocardium limits the efficacy of cardiac repair after myocardial infarction (MI). Chitosan-based scaffolds have emerged as functional biomaterials for designing delivery systems in cardiac therapies. This study aimed to enhance the potency of cardiac repair using a hiPSC-CMs loaded chitosan cardiac muscle patch (hCCMP). Methods: The patches were fabricated using chitosan. Characterization of the chitosan patches involved assessing their swelling rate and porosity. The biocompatibility of the hCCMP was analyzed through scanning electron microscopy (SEM) and the CCK8 assay. 16 Yorkshire swine (15-20 kg, 45-50 days of age) were randomly divided into 4 groups (n=4 per group): Sham, MI without further intervention, MI with an empty patch (without hiPSC-CMs), and MI with hCCMP implantation. One and four weeks post-MI, heart function, Infarction size, myocardial perfusion and metabolism were evaluated via cardiac PET-MRI. Engraftment was assessed through human cardiac troponin T staining. Histological analysis including left ventricular anterior wall thickness, cardiac remodeling, angiogenesis, arterialization, and apoptosis in the infarct border area were analyzed using immunofluorescence. Results: SEM showed that the chitosan patch had regular pore size and good 3D structure; porosity was about (96.7±0.37)%. On day3, the patch swelling rate was about (715±64.55)%. SEM, CCK8 assay showed a normal cells growth in the chitosan patch. The hiPSC-CMs grafted well with chitosan patch delivery systems and was associated with significantly improvement in LV function, infarction size, angiogenesis and cardiomyocyte apoptosis in pigs 4 weeks after MI. Conclusions: The 3D chitosan cardiac patch with hiPSC-CMs loaded can enhance the potency of cardiac repair in pigs after MI and present a novel and promising therapic strategy.

Abstract 4135531: The Ubiquitin-Specific Protease 30 Inhibitor, MTX652, Attenuates Cardiac Dysfunction And Remodelling In a Murine Model Of Transverse Aortic Constriction

Introduction: Mitochondrial abnormalities are a characteristic of heart failure leading to energy deprivation and disease worsening. The mitochondrial deubiquitinating enzyme USP30, removes ubiquitin and represses PINK1/PARKIN-mediated mitophagy leading to accumulation of dysfunctional mitochondria. In this study we investigated the role of MTX652, a clinical stage USP30 inhibitor, in a mouse model of cardiac hypertrophy using transverse aortic constriction (TAC). Hypothesis: Inhibition of USP30 will promote mitophagy resulting in clearance of dysfunctional mitochondria and improved cellular health leading to cardioprotective effects. Aims: To determine if MTX652 can protect from TAC induced cardiac hypertrophy and remodelling. Methods: Male C57BL/6 mice, 8 weeks old, were subjected to sham surgeries or TAC using a 26G needle to induce cardiac pressure overload. MTX652 (1.5 or 5 mg/kg, n =12-13) or vehicle ( n =11) was administered orally, twice daily, starting 2 days post-surgery. Captopril (30 mg/kg/d, n =13) was also included as a positive control. After 4 weeks, echocardiography assessed left ventricle (LV) function and morphology. Cell based assays assessed MTX652 target engagement and TOM20 ubiquitination in vitro. Results: LV hypertrophy and wall thickening was observed in TAC animals. Treatment with MTX652 decreased systolic LV volume (1.5 mg/kg p&lt;0.05 and 5 mg/kg p&lt;0.01) and diameter (1.5 mg/kg p&lt;0.01 and 5 mg/kg p&lt;0.05,) demonstrating comparable effects to Captopril. A reduction in anterior wall thickness in diastole was also observed with MTX652 (5 mg/kg, p&lt;0.01). Cardiac dysfunction was also evident in TAC animals with MTX652 showing improvements in both ejection fraction (1.5 mg/kg and 5 mg/kg, p&lt;0.0001) and fractional shortening (1.5 mg/kg and 5 mg/kg, p&lt;0.0001). Cellular target engagement for MTX652 was confirmed in HeLa-YFP-Parkin cells with an EC 50 of 2.7 nM ( n =2). Furthermore, the USP30 substrate TOM20 was ubiquitinated following MTX652 treatment in vitro (EC 50 =6.1 nM, n =4) providing evidence of mitophagy activation, a finding also confirmed in mouse heart tissue (MTX652, 5mg/kg). Conclusions: The USP30 inhibitor, MTX652 significantly protected mice from TAC induced cardiac hypertrophy and LV dysfunction. Furthermore, MTX652 potentiates ubiquitylation of TOM20 as a mechanism to promote mitophagy. These data suggest our clinical stage molecule could provide a novel therapeutic approach for the treatment of cardiac hypertrophy and heart failure.

Abstract 4112944: A diagnostic challenge overcome with persistent clinical suspicion in a case of cardiac AL amyloidosis

Case: A 62-year old male with a history of chronic kidney disease and paroxysmal atrial fibrillation presented with several months of fatigue, a progressive decline in functional status (NYHA IIIb-IV), weight loss, and intermittent lower extremity swelling. Blood pressure was 92/72 mmHg on presentation, and heart rate was 90 bpm. Physical examination revealed a jugular venous pressure of 12-14 cm H2O and 2+ bilateral lower extremity edema with mild wheezing. Methods/workup: Laboratories are shown in Table 1 and were notable for a serum free light chain ratio of 0.14. Transthoracic echocardiogram (figure 1) revealed a left ventricular (LV) ejection fraction of 33% with increased LV wall thickness and severe bi-atrial enlargement. Bone marrow biopsy revealed 2% lambda restricted plasma cells without evidence of amyloid deposits; metastatic bone survey was negative. A fat pad biopsy and endomyocardial biopsy stained negative for amyloid with Congo red. Cardiac MRI showed diffuse, circumferential subendocardial late gadolinium enhancement, most compatible with cardiac amyloidosis (figure 2). The patient also had a chest CT scan that demonstrated a few patchy nodular pulmonary infiltrates. Given his extensive negative workup, he was referred to pulmonary and endobronchial biopsy was positive for amyloid on Congo red staining (figure 3). Biopsy tissue typing revealed Lambda subtype AL amyloidosis. Management: The patient was started on Daratumumab, Cyclophosphamide, Bortezomib, and Dexamethasone by Hematology. Unfortunately, about a month after his diagnosis, he developed worsening heart failure despite treatment. He was admitted to an outside hospital with refractory cardiogenic shock and passed away during that admission. Discussion: The diagnosis of AL amyloidosis requires a high index of suspicion for prompt diagnosis and treatment. We present a case in which cardiac amyloidosis was suspected based on the patient’s clinical picture and cardiac imaging; however, multiple initial biopsies were negative. An expedited, multimodal and interdisciplinary diagnostic assessment is imperative as prognosis with chemotherapy is highly dependent on extent of AL disease, patient functional status, and presence of cardiac compromise. Elevated natriuretic peptides, troponins, autonomic dysfunction, and hypotension are negative prognostic features.

Abstract 4140118: Identification of Obstructive and Non-Obstructive Hypertrophic Cardiomyopathy Patients Using Natural Language Processing in a Large Integrated Healthcare System

Introduction: Accurately identifying and characterizing patients with hypertrophic cardiomyopathy (HCM) is critical for population management and care optimization. Research Question: To develop natural language processing (NLP) algorithms to identify and characterize obstructive (oHCM) and non-obstructive (nHCM) HCM patients directly from echocardiograms, and to compare with the presence or absence of HCM-related diagnosis codes. Methods: We developed and validated NLP algorithms to identify HCM from all adult (age≥18yrs) echocardiograms performed from 2010-2019 in Kaiser Permanente Northern CA (KPNC), capturing measures of any HCM, HCM subtype, hypertrophy subtype, septal and posterior LV wall thickness, resting and stress/Valsalva LVOT gradients, and systolic anterior motion. We developed a rules-based algorithm (following AHA/ACC criteria) to classify patients as having HCM, including oHCM or nHCM subtypes, and possible HCM (defined as wall thickness ≥2cm without other criteria meeting an HCM definition). We evaluated the presence of HCM-related ICD-9/10 diagnosis codes among patients classified as HCM/non-HCM from echocardiograms using NLP, and linked baseline demographics and clinical parameters from our integrated electronic medical record. Results: Among 472,405 adults with echocardiograms, we identified 2,892 patients with HCM based upon NLP-derived measures (all NLP measures achieved &gt;95% positive predictive value and &gt;95% negative predictive value), including 1,585 (55%) with oHCM, 1,145 (40%) with nHCM, and 162 (6%) which could not be classified (Figure). Among those 2,892 patients, 1,283 did not have any associated HCM ICD-9/10 diagnosis codes (Table). Among 469,513 patients with no identified HCM from NLP-based algorithms, HCM ICD-9/10 diagnosis codes existed in 1,567 patients (Table). We also identified 4,593 patients with possible HCM by NLP, only 4.5% of whom had an associated HCM code. Among confirmed HCM patients by NLP, oHCM patients were slightly older (66 vs 61 yrs), more likely female (53% vs 43%), had similar mean septal wall thickness (1.7cm vs 1.7cm), but were more likely to have a septal hypertrophy subtype (46% vs 28%) compared to nHCM patients. Conclusions: Echocardiogram-based NLP methods can improve the identification of and care for HCM patients. Many patients with possible HCM may be underdiagnosed, representing an opportunity for quality improvement.

Loss of quality of life and increased societal costs in patients with hypertrophic cardiomyopathy: the AFFECT-HCM study.

Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited cardiac disease. The impact of HCM on quality of life (QoL) and societal costs remains poorly understood. This prospective multi-centre burden of disease study estimated QoL and societal costs of genotyped HCM patients and genotype-positive phenotype-negative (G+/P-) subjects. Participants were categorized into three groups based on genotype and phenotype: 1) G+/P- (left ventricular (LV) wall thickness <13 mm), 2) non-obstructive HCM (nHCM, LV outflow tract (LVOT) gradient <30 mmHg), and 3) obstructive HCM (oHCM, LVOT gradient ≥30 mmHg). We assessed QoL with EQ-5D-5L and Kansas City Cardiomyopathy Questionnaires (KCCQ). Societal costs were measured using medical consumption (iMCQ) and productivity cost (iPCQ) questionnaires. We performed subanalyses within three age groups: <40, 40-59, and ≥60 years. From three Dutch hospitals, 506 subjects were enrolled (84 G+/P-, 313 nHCM, 109 oHCM; median age 59 years, 39% female). HCM (both nHCM and oHCM) patients reported reduced QoL vs G+/P- subjects (KCCQ: 88 vs 98, EQ-5D-5L: 0.88 vs 0.96; both p<0.001). oHCM patients reported lower KCCQ scores than nHCM patients (83 vs 89, p=0.036). Societal costs were significantly higher in HCM patients (€19,035/year vs €7,385/year) compared to G+/P- controls, mainly explained by higher healthcare costs and productivity losses. Being symptomatic and of younger age (<60 years) particularly led to decreased QoL and increased costs. HCM is associated with decreased QoL and increased societal costs, especially in younger and symptomatic patients. oHCM patients were more frequently symptomatic than nHCM patients. This study highlights the substantial disease burden of HCM and can aid in assessing new therapy cost-effectiveness for HCM in the future.

Prevalence of transthyretin cardiac amyloidosis in undifferentiated heart failure with preserved ejection fraction.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasinglyrecognized cause of heart failure with preserved ejection fraction (HFpEF), which may be diagnosed non-invasively using 99 mTc 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scintigraphy-based diagnostic criteria. Our aim was to determine the prevalence of ATTR-CM in an undifferentiated HFpEF cohort with a DPD scintigraphy-based screening protocol. Patients with HFpEF [ejection fraction (EF) ≥50%] aged ≥60years and no prior evaluation for cardiac amyloidosis or known monoclonal gammopathy attending a regional cardiology network were screened with DPD scintigraphy. Patients with positive myocardial uptake (Perugini grade 2 or 3) were tested for a monoclonal protein and transthyretin gene variant. Eighty-six subjects were prospectively enrolled: 56% female, mean age 77±8years, 63% New York Heart Association (NYHA) Class III and median N-terminal pro-brain natriuretic peptide (NT-proBNP) 1766ng/L [inter-quartile range (IQR) 731-3703]. DPD scintigraphy was positive in seven patients (8%). Monoclonal gammopathy of undetermined significance was present in one out of seven patients, and no pathogenic TTR gene variant was identified. The prevalence of wild-type ATTR-CM was 8% of this cohort. Compared with the HFpEF DPD scintigraphy-negative cohort, DPD scintigraphy-positive patients were older (86±3 vs. 76±8years), more frequently male (16% vs. 2%, P=0.02), and had significantly greater left ventricular (LV) wall thickness (16 vs. 12mm; P=0.002) and higher high-sensitivity troponin levels at diagnosis [78ng/L (IQR 21-116) vs. 11ng/L (IQR 9-17); P<0.001]. In an undifferentiated HFpEF cohort, 8% were found to have wild-type ATTR-CM using a DPD scintigraphy-based screening protocol. Screening undifferentiated HFpEF patients is associated with a significant diagnostic yield, which can be further increased by targeting older males with increased LV wall thickness and elevated high-sensitivity troponin levels.

Epidemiological Profile and Correlates for Left Ventricular Diastolic Dysfunction among Patients Attending a Tertiary Health Facility in India

Background: There is an increasing recognition that congestive heart failure (CHF), caused by diastolic dysfunction (DD) (diastolic heart failure), is common and causes significant morbidity and mortality. Methods: The institution-based cross-sectional study was conducted among 119 subjects to determine the epidemiological profile, and regression analysis was used to evaluate the association of clinico-social correlates with the likelihood of developing DD. Result: The mean age of subjects was 51.6(±17.7) years. The mean systolic (SBP) and diastolic blood pressures (DBP) were 130(±18.9) mm Hg and 82.1(±11.1) mm Hg, respectively. Thirty-three (27.7%) subjects were hypertensive. Twelve (10%) were diabetic and experienced heart failure. DD was present in 54 (45.4%) subjects. Age, diabetes, ejection fraction (EF), and interventricular septal thickness in diastole (IVSd) were significant (P &lt; 0.05) correlates of DD. Mean values of age, body mass index (BMI), EF, IVSd, and left ventricular posterior wall thickness in diastole (LVPWD) were higher in subjects with DD. Hypertension contributed to 1.63 times greater odds of developing DD. Conclusion: The prevalence of DD increased with age among hypertensive and diabetic participants. Preventive strategies directed toward identifying subclinical signs of early stage and aggressive blood pressure and blood sugar control are likely to offer the greatest promise for reducing the incidence of DD.

Factors Predicting Fetal Growth Restriction and Fetal Cardiac Remodeling.

This study aimed to investigate factors influencing fetal growth restriction (FGR) occurrence and assess the clinical significance of fetal cardiac parameters in FGR prediction. Pregnant women with clinically suspected FGR (n=179) and uncomplicated pregnancies (n=53) were included. All had undergone routine obstetric ultrasonography and fetal echocardiography. Umbilical artery flow (UAF) and fetal cardiac parameters (left atrial transverse diameter (LAd), right atrial transverse diameter (RAd), left ventricular transverse diameter (LVd), right ventricular transverse diameter (RVd), foramen ovale width, atrial septum diameter, interventricular septal thickness, left ventricular posterior wall thickness, right ventricular free wall thickness, aortic diameter, pulmonary artery diameter, mitral E velocity, mitral A velocity, tricuspid E velocity, tricuspid A velocity, aortic valve peak flow velocity, and pulmonary valve peak flow velocity) were detected. Follow up was conducted until birth, various fetal clinical parameters were collected: maternal body mass index (BMI), hypertensive disorders complicating pregnancy (HDCP), abnormal umbilical artery flow, placental or umbilical cord anomalies, low amniotic fluid volume, preterm birth, emergency cesarean delivery, maternal height, maternal age, gestational diabetes mellitus (GDM), hypothyroidism, assisted reproductive technology (ART), parity, and neonatal gender. Participants were categorized into confirmed FGR (n=119) and control (n=113) groups based on neonatal birth weight. Significant differences were observed between groups in maternal BMI, HDCP, abnormal UAF, placental or umbilical cord anomalies, low amniotic fluid volume, preterm birth, and emergency cesarean delivery. FGR was positively related to abnormal UAF, placental or umbilical cord anomalies, preterm birth and emergency cesarean delivery and negatively to maternal BMI (r=-0.276). Compared to the control group, the FGR group exhibited significantly larger RAd, RVd, RA/LA, and RV/LV. Fetal growth-restricted fetuses have enlarged right heart structures. Fetal cardiac examinations are valuable for early FGR diagnosis, potentially improving neonatal body weight and reducing adverse pregnancy outcomes.

Identification of a Missense Mutation in the FLNC Gene from a Chinese Family with Restrictive Cardiomyopathy.

Restrictive cardiomyopathy (RCM) is a heterogenous cardiomyopathy with various causes, and genetic variants take an important part of the pathogenesis. Whole-exome sequencing (WES) is effective to discover genes that cause genetic diseases. By using WES, we attempted to identify the genetic cause of an RCM family and clarify the clinical diagnosis of the patient and then provide a personalized treatment plan. Blood samples were obtained from the proband and his healthy parents. WES and Sanger sequencing were performed to identify the possible pathogenic gene. Co-segregation analysis was conducted for candidate variants, and the allele frequency was checked in databases including Ensembl, Exome Aggregation Consortium (ExAC) and Human Gene Mutation Database (HGMD). Furthermore, the potential effect of variant was predicted using various-free software such as SIFT, Polyphen-2 and Mutation Taster and the conservation was tested using multiple sequence alignments by ClustalX. The proband was a 20 years old boy with severe heart failure symptoms including dyspnea, massive ascites, edema of both lower limbs and chestcongestion. Echocardiography showed significant biatrial enlargement, normal left ventricular wall thickness and preserved systolic function of both ventricles. A missense mutation in FLNC (c.6451G>A, p.G2151S), encoded filamin-C was detected in proband by WES and Sanger sequencing, while it was not be found in his parents, we supposed that the FLNC mutation (c.6451G>A, p.G2151S) may be a de-novo mutation. Through multiple functional predictions, we found that it is a deleterious mutation and the mutation in filamin-C could alter its structure and normal function, contributing to RCM. Here, an FLNC missense mutation (c.6451G>A, p.G2151S) known to be pathogenic in hypertrophic cardiomyopathy, was found to be associated with RCM, indicating the genetic overlap among cardiomyopathies. This study provides insights into Phenotype-Genotype Correlations of RCM in patients with FLNC mutations.

A review of alternative measurements in strain imaging for ventricular arrhythmia prediction.

Global longitudinal strain has been established as a reliable tool to assess global left ventricular function and a marker of subclinical left ventricular dysfunction unrecognized by the ejection fraction. On the other hand, ventricular arrhythmias are the most common cause of sudden cardiac death. Their early detection is a challenge. Possible prognostic markers for the risk of ventricular arrhythmias are discussed in the literature - electrocardiographic, cardiac magnetic resonance, computed tomography, radionuclide imaging, and markers from new echocardiographic techniques. Of the latter, at this stage of knowledge, several markers have been discussed as informative for predicting ventricular arrhythmias - global longitudinal strain, radial strain and mechanical dispersion, and most recently, myocardial work. As far as we are informed, global longitudinal strain is particularly useful in patients with normal echocardiographic parameters such as left ventricular ejection fraction, left atrial diameter, left ventricular wall thickness, and aortic root. The relationship between mechanical dispersion and ventricular arrhythmias has been widely studied. The relationship has been studied more in some patient populations - heart failure, ischemic heart disease, long QT syndrome and arrhythmogenic cardiomyopathy, congenital heart disease. The role of mechanical dispersion as a predictor of ventricular arrhythmias in metabolic syndrome is scarce.

Left atrial function in uraemic patients: Four-dimensional automatic left atrial quantitative technology study.

This study aimed to evaluate the utility of left atrial volume and function in uraemic patients using four-dimensional automatic left atrial quantification (4D auto LAQ) technology. Thirty-four undialysed uraemic patients (U-ND group), 60 dialysed uraemic patients (U-D group), and 32 healthy volunteers (N group) were enrolled in our current study. Conventional echocardiographic parameters were recorded, and left atrial volume and strain parameters were analysed to determine statistical differences among the three groups. The Pearson correlation coefficient was employed to assess the relationships between left atrial ejection fraction and left atrial strain parameters. Compared to the N group, uraemic patients often displayed left atrial enlargement and left ventricular hypertrophy. Significant increases were noted in left atrial diameter, interventricular septum thickness, left ventricular posterior wall thickness, E/e', diastolic blood pressure, systolic blood pressure, left atrial minimum volume, left atrial maximum volume, left atrial pre-atrial contraction volume, left atrial emptying volume and left atrial maximum volume index (P<0.05). Conversely, the e', E/A ratio and left atrial reservoir longitudinal strain were significantly decreased (P<0.05). However, no statistically significant differences were observed in the aforementioned parameters between the U-ND and U-D groups. The absolute values of left atrial conduit longitudinal strain and left atrial conduit circumferential strain, as well as left atrial passive ejection fraction, were notably lower in the U-D group compared to the N and U-ND groups, with statistically significant differences identified among the three groups (P<0.05). Uraemic patients exhibit marked left atrial enlargement and left ventricular hypertrophy, coupled with altered atrial function, particularly ductal dysfunction in the U-D group. The 4D auto LAQ technology proves advantageous in detecting these alterations, offering a promising tool for thorough cardiac assessment in this patient cohort.

Deep learning for fully automated echocardiographic measurements of left ventricular wall thickness and chamber dimensions in the parasternal long-axis view

Abstract Background Accurate quantification of left ventricular (LV) wall thickness and chamber dimensions in the echocardiographic parasternal long-axis view (PLAX) is crucial for clinical decisions in patients with heart disease. However, there is a need for more reproducible and time-efficient methods. Fully automated deep learning (DL)-based methods could address this need. Purpose To develop a DL-based method for fully automated measurements of LV wall thickness and chamber dimensions in PLAX, validate its performance in a large population cohort, and evaluate its capacity to differentiate between hypertensive and normotensive groups. Methods DL networks were trained on PLAX recordings from 207 subjects. The DL method performed cardiac segmentation, timing of end-systole and end-diastole, and measured LV wall thickness and chamber dimensions in PLAX. The model was validated in a large populational echocardiography dataset including a subset with test-retest evaluation. Agreement with expert reference measurements, test-retest reproducibility, and comparison of normotensive and hypertensive (defined as those on hypertensive medication or with systolic blood pressure &amp;gt;160 mmHg) groups were evaluated. Results In the populational study of 2047 subjects, the novel DL method demonstrated a feasibility of 97.6%. Strong agreement was observed between the automated DL method and expert readers in measuring end-diastolic septal thickness, posterior wall thickness, and LV diameter (bias 0.1 mm, 0.2 mm, and 2.2 mm, respectively, Figure 1). In a test-retest dataset (n=40, with 2 recordings per patient and 4 readers), the novel DL method displayed improved reproducibility compared to inter-reader measurements, with minimal detectable change for interventricular septal diameter 2.2 mm versus 2.6 mm, posterior wall diameter 1.2 mm versus 2.5 mm, and LV diameter 5.0 mm versus 6.3 mm (Figure 2). The DL method measured significantly wider septal diameter in the hypertensive group compared to normotensive group (p&amp;lt;0.001). Mean analysis time for wall thickness and chamber dimensions using the DL method was 1.2 seconds. Conclusion The novel DL method accurately measured LV wall thickness and chamber dimensions in the PLAX view, and demonstrated improved test-retest reproducibility compared to experienced echocardiographers. Additionally, it was able to detect significantly wider septal diameters in the hypertensive population. By providing fast and reliable measurements in retrospective data, and with potential for real-time measurements during image acquisition, this DL method has the potential to improve the yield, efficiency, and workflow in echocardiography.Bland-Altman posterior wall diameterTest-retest posterior wall diameter

Structural echocardiographic parameters in male and female Asian athletes: a systematic review and meta-analysis

Abstract Introduction Following repetitive structured and intense physical training, elite athletes’ hearts undergo physiological cardiac remodelling, including increased left ventricular (LV) size and LV wall thickness. These changes may mimic those seen in pathological cardiac conditions such as dilated and hypertrophic cardiomyopathy, posing a challenge for accurate diagnosis. Reference ranges for common echocardiographic parameters in elite Caucasian and Black athletes have been reported, facilitating differentiation between physiological and pathological changes in these demographics. However, there remains a paucity of data for Asian athletes despite their increasing representation in global sport. Methods We searched MEDLINE via PubMed, Embase, and the Cochrane Database for relevant studies from inception till 20th November 2023. We included observational studies that reported relevant echocardiographic parameters in elite Asian athletes. Studies that did not report gender-specific cardiac imaging parameters were excluded. After study selection and data extraction, random-effects meta-analysis of means was performed to obtain the weighted mean and 95% confidence intervals (CI) of common echocardiographic parameters stratified by gender. Results Our final search yielded 10 studies comprising a total of 1,111 elite athletes (996 male, 115 female; 53% Japanese, 21% uncategorised, 14% South-East Asian). Athletes participating in skill and power disciplines were excluded from analysis post-hoc due to a paucity of data and extreme data ranges. In male athletes, mean LV wall thickness was 9.4 mm (95% CI 8.5-10.3, I2 = 98.9%), mean LV end diastolic diameter was 54.7 mm (95% CI 52.5-57.0, I2 = 98.6%), mean LV mass indexed to body surface area was 97.5 g/m2 (95% CI 90.5-104.5, I2 = 97.5%) and mean aortic root diameter was 31.9 mm (95% CI 29.2-34.7, I2 = 99.5%). In female athletes, mean LV wall thickness was 7.9 mm (95% CI 7.5-8.4, I2 = 85.4%), mean LV end diastolic diameter was 47.1 mm (95% CI 45.8-48.3, I2 = 77.3%), mean LV mass indexed to body surface area was 79.5 g/m2 (95% CI 69.2-89.7, I2 = 92.8%) and mean aortic root diameter was 27.5 mm (95% CI 26.9-28.1). Conclusion This meta-analysis describes commonly reported echocardiographic parameters in elite Asian athletes from endurance and mixed sport disciplines. The absolute values of all reported parameters appear to fall far below reported limits for non-Asian athletes, highlighting substantial ethnic and regional variation in cardiac remodelling in elite athletes. While our results facilitate preliminary referencing of expected normal ranges in this demographic group, further studies are necessary to fully define the cardiac characteristics of Asian athletes.