A Deep Learning Approach to Classify Fabry Cardiomyopathy from Hypertrophic Cardiomyopathy Using Cine Imaging on Cardiac Magnetic Resonance.

A challenge in accurately identifying and classifying left ventricular hypertrophy (LVH) is distinguishing it from hypertrophic cardiomyopathy (HCM) and Fabry disease. The reliance on imaging techniques often requires the expertise of multiple specialists, including cardiologists, radiologists, and geneticists. This variability in the interpretation and classification of LVH leads to inconsistent diagnoses. LVH, HCM, and Fabry cardiomyopathy can be differentiated using T1 mapping on cardiac magnetic resonance imaging (MRI). However, differentiation between HCM and Fabry cardiomyopathy using echocardiography or MRI cine images is challenging for cardiologists. Our proposed system named the MRI short-axis view left ventricular hypertrophy classifier (MSLVHC) is a high-accuracy standardized imaging classification model developed using AI and trained on MRI short-axis (SAX) view cine images to distinguish between HCM and Fabry disease. The model achieved impressive performance, with an F1-score of 0.846, an accuracy of 0.909, and an AUC of 0.914 when tested on the Taipei Veterans General Hospital (TVGH) dataset. Additionally, a single-blinding study and external testing using data from the Taichung Veterans General Hospital (TCVGH) demonstrated the reliability and effectiveness of the model, achieving an F1-score of 0.727, an accuracy of 0.806, and an AUC of 0.918, demonstrating the model's reliability and usefulness. This AI model holds promise as a valuable tool for assisting specialists in diagnosing LVH diseases.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Echocardiography-Based Deep Learning Model to Differentiate Constrictive Pericarditis and Restrictive Cardiomyopathy.

BACKGROUND: Constrictive pericarditis (CP) is an uncommon but reversible cause of diastolic heart failure if appropriately identified and treated. However, its diagnosis remains a challenge for clinicians. Artificial intelligence may enhance the identification of CP. OBJECTIVES: The authors proposed a deep learning approach based on transthoracic echocardiography to differentiate CP from restrictive cardiomyopathy. METHODS: Patients with a confirmed diagnosis of CP and cardiac amyloidosis (CA) (as the representative disease of restrictive cardiomyopathy) at Mayo Clinic Rochester from January 2003 to December 2021 were identified to extract baseline demographics. The apical 4-chamber view from transthoracic echocardiography studies was used as input data. The patients were split into a 60:20:20 ratio for training, validation, and held-out test sets of the ResNet50 deep learning model. The model performance (differentiating CP and CA) was evaluated in the test set with the area under the curve. GradCAM was used for model interpretation. RESULTS: A total of 381 patients were identified, including 184 (48.3%) CP, and 197 (51.7%) CA cases. The mean age was 68.7 ± 11.4 years, and 72.8% were male. ResNet50 had a performance with an area under the curve of 0.97 to differentiate the 2-class classification task (CP vs CA). The GradCAM heatmap showed activation around the ventricular septal area. CONCLUSIONS: With a standard apical 4-chamber view, our artificial intelligence model provides a platform to facilitate the detection of CP, allowing for improved workflow efficiency and prompt referral for more advanced evaluation and intervention of CP.

Patisiran Treatment in Patients with Transthyretin Cardiac Amyloidosis.

BACKGROUND: Transthyretin amyloidosis, also called ATTR amyloidosis, is associated with accumulation of ATTR amyloid deposits in the heart and commonly manifests as progressive cardiomyopathy. Patisiran, an RNA interference therapeutic agent, inhibits the production of hepatic transthyretin. METHODS: In this phase 3, double-blind, randomized trial, we assigned patients with hereditary, also known as variant, or wild-type ATTR cardiac amyloidosis, in a 1:1 ratio, to receive patisiran (0.3 mg per kilogram of body weight) or placebo once every 3 weeks for 12 months. A hierarchical procedure was used to test the primary and three secondary end points. The primary end point was the change from baseline in the distance covered on the 6-minute walk test at 12 months. The first secondary end point was the change from baseline to month 12 in the Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) score (with higher scores indicating better health status). The second secondary end point was a composite of death from any cause, cardiovascular events, and change from baseline in the 6-minute walk test distance over 12 months. The third secondary end point was a composite of death from any cause, hospitalizations for any cause, and urgent heart failure visits over 12 months. RESULTS: A total of 360 patients were randomly assigned to receive patisiran (181 patients) or placebo (179 patients). At month 12, the decline in the 6-minute walk distance was lower in the patisiran group than in the placebo group (Hodges-Lehmann estimate of median difference, 14.69 m; 95% confidence interval [CI], 0.69 to 28.69; P = 0.02); the KCCQ-OS score increased in the patisiran group and declined in the placebo group (least-squares mean difference, 3.7 points; 95% CI, 0.2 to 7.2; P = 0.04). Significant benefits were not observed for the second secondary end point. Infusion-related reactions, arthralgia, and muscle spasms occurred more often among patients in the patisiran group than among those in the placebo group. CONCLUSIONS: In this trial, administration of patisiran over a period of 12 months resulted in preserved functional capacity in patients with ATTR cardiac amyloidosis. (Funded by Alnylam Pharmaceuticals; APOLLO-B ClinicalTrials.gov number, NCT03997383.).

Symptom-limited exercise capacity is associated with long-term survival.

The prognostic value of exercise capacity has been demonstrated in subjects with established cardiovascular diseases. We aim to evaluate the independence of exercise capacity measured by treadmill exercise test (TET) in predicting long-term outcomes among various comorbidities. This study was conducted from January 2003 to December 2012 in a tertiary medical center in Taiwan. Subjects referred for symptom-limited TET were recruited. Peak achieved metabolic equivalents (METs) were determined by treadmill grade and speed at peak exercise. The main outcomes were cardiovascular and all-cause mortality by linking to the National Death Registry. A total of 18,954 participants (57.8 ± 12.8 years, 62% men) achieved a mean peak METs of 9.2. Subjects in the lowest tertile of peak METs were older, had poorer renal function, lower hemoglobin, and more comorbidities. During a median follow-up of 4.3 years, there were 642 mortalities and 132 cardiovascular deaths. Peak METs significantly predicted cardiovascular death and all-cause mortality in the multivariable Cox regression models [hazard ratio (95% confidence intervals): 0.788 (0.660-0.940) and 0.835 (0.772-0.903), respectively]. The prognostic influence of peak METs consistently appeared in the subgroups, regardless of age, gender, body weight, comorbidities, use of beta-blockers, or the presence of exercise-induced ischemia. The fitness was more predictive of long-term outcomes in young or those with ischemic changes during TET (P for interaction: 0.035 and 0.018, respectively). The benefit of fitness was nonlinearly associated with long-term survival. The prognostic impacts of exercise capacity were universally observed in subjects with or without various comorbidities.

Surgery for severe mitral regurgitation: The etiology matters.

BACKGROUND: While surgery has been the standard treatment for patients with severe primary mitral regurgitation (PMR), the role of surgery for severe secondary mitral regurgitation (SMR) remained debated. We therefore investigated the prognostic differences of surgery for patients with either severe PMR or SMR. METHODS: Subjects hospitalized for heart failure were enrolled from 2002 to 2012. The severity of MR was assessed by continuity equation, and an effective regurgitant orifice area of ≥40 mm 2 was defined as severe. Long-term survival was then identified by the National Death Registry. RESULTS: A total of 1143 subjects (66.4 ± 16.6 years, 65% men, and 59.7% PMR) with severe MR were analyzed. Compared with PMR, patients with SMR were older, had more comorbidities, greater left atrial and ventricular diameter, and less left ventricular ejection fraction (all p < 0.05). While 47.8% of PMR patients received mitral valve surgery, only 6.9% of SMR patients did. Surgical intervention crudely was associated with 54% reduction of all-cause mortality in PMR (hazard ratio, 0.46; 95% confident interval, 0.32-0.67), and 48% in the subpopulation with SMR (0.52, 0.30-0.91). Propensity score matching analysis demonstrated the survival benefits of mitral valve surgery was observed in patients with PMR (log rank p = 0.024), but not with SMR. Among the unoperated subjects, age, renal function, and right ventricular systolic pressure were common risk factors of mortality, regardless of MR etiology. CONCLUSION: Mitral valve surgery for patients with heart failure and severe MR was associated with better survival in patients with PMR, but not in those with SMR.

2023 Expert Consensus of the Taiwan Society of Cardiology on the Diagnosis and Treatment of Cardiac Amyloidosis.

Cardiac amyloidosis is one form of systemic amyloidosis caused by abnormal amyloid fibrils deposited in the extracellular space of the myocardium causing heart failure because of restrictive cardiomyopathy and conduction disturbances. The incidence and prevalence of cardiac amyloidosis are higher than previously noted, particularly among special populations. The most common forms of cardiac amyloidosis are light chain and transthyretin amyloid cardiomyopathy. Even though more than 70% of patients with systemic amyloidosis have cardiac amyloidosis, the diagnosis is often delayed, suggesting significant gaps in the knowledge of cardiac amyloidosis and a lack of multidisciplinary teamwork in our daily practice. The Taiwan Society of Cardiology Heart Failure Committee organized experts to draft the "Expert Consensus on the diagnosis and treatment of cardiac amyloidosis." This statement aims to help clinicians and healthcare professionals improve early diagnosis and management of cardiac amyloidosis in Taiwan. The expert panel met virtually to review the data and discuss the consensus statements. Our review provided practical information about diagnostic methods and algorithms, clinical clues and red-flag signs, cardiac amyloidosis per se and its comorbidities treatment modalities, and follow-up plans for asymptomatic transthyretin gene carriers. We especially innovate two acronyms, "HFpEF MUTED CALL" and "HFmrEF MUST COUNT", to help in the early diagnosis and screening of transthyretin amyloid cardiomyopathy as shown in the Central Illustration.

Pitfalls for the non-invasive diagnosis of wild-type transthyretin amyloid cardiomyopathy in a young adult: a case report.

Background: Using technetium (Tc)-labelled pyrophosphate (PYP) cardiac scintigraphy, a non-invasive diagnosis of transthyretin amyloid (ATTR) cardiomyopathy can be made without histopathological confirmation. In patients suspected of ATTR cardiomyopathy, however, atypical presentations may necessitate further investigation. Case summary: A 30-year-old man with hypertension and end-stage renal disease on peritoneal dialysis presented with progressive exertional dyspnoea. Left ventricular hypertrophy (LVH) with a maximal end-diastolic wall thickness up to 16 mm was detected on echocardiography. Speckle-tracking analysis revealed a reduced longitudinal strain of left ventricle with a relative apical sparing pattern. Although the absence of monoclonal gammopathy, a grade 3 myocardial uptake in 99mTc-PYP cardiac scintigraphy, and negative TTR gene mutation inferred the diagnosis of wild-type ATTR, the relative youth of the patient still raised concerns regarding the diagnosis. Under clinical doubt, he underwent further testing. In non-contrast cardiac magnetic resonance (CMR) with native T1 mapping, the native T1 myocardial value was within the normal range. In endomyocardial biopsy (EMB), there was no evidence of amyloid deposition, negative Congo red staining, and no immunohistochemical evidence of transthyretin expression. These results excluded the diagnosis of ATTR cardiomyopathy and prevented subsequent unnecessary treatments. Discussion: When patients with unexplained LVH meet the non-invasive diagnostic criteria for ATTR cardiomyopathy, an EMB should be considered in selected cases. Patients presenting at an atypical age for wild-type ATTR cardiomyopathy, absence of extracardiac symptoms/signs or classic electrocardiogram features for cardiac amyloidosis should be suspected of another diagnosis and require further CMR or EMB to confirm.

Elevated serum levels of T-cell immunoglobulin and mucin-domain containing molecule 3 in patients with systemic inflammation following COVID-19 vaccination.

BACKGROUND: ChAdOx1 nCoV-19 vaccine has been widely used. Some unexpected adverse effects such as the development of systemic hyper inflammation with multiorgan involvement after vaccination, in rare cases, have been reported. However, its pathogenesis remains unclear. METHODS: This study recruited two cases who suffered from systemic inflammation following ChAdOx1 nCoV-19 vaccine and two 30-year-old male volunteers without underlying disease who have received ChAdOx1 nCoV-19 vaccine as control group. Blood samples were collected from our patients and healthy subjects before and after treatment with anti-inflammatory agent such as glucocorticoid and tocilizumab. The immune profile from our patients and healthy controls were measured using a human XL cytokine Proteome Profiler array (ARY022b, R&D Systems). RESULTS: Biochemical parameters revealed leukocytosis with segmented neutrophil dominance and elevated serum levels of C-reactive protein (CRP), erythrocyte sedimentation rate, and ferritin in these two patients. The cytokine array revealed that mean levels of T cell immunoglobulin and mucin-domain containing-3 (TIM-3) (3640.3 vs 1580.5 pixels per inch [ppi]), B-cell activating factor (BAFF) (3036.8 vs 1471.0 ppi), urokinase plasminogen activator surface receptor (uPAR) (1043.1 vs 516.8 ppi), Resistin (1783.7 vs 711.3 ppi), platelet-derived growth factor (PDGF)-AB/BB (1980.7 vs 939.7 ppi), macrophage inflammatory protein-3-beta (MIP-3ß) (911.9 vs 346.2 ppi), and interferon-inducible T-cell alpha chemoattractant (I-TAC) (1026.3 vs 419.7 ppi) were 2-fold higher in the patients than in normal subjects who received ChAdOx1 nCoV-19 vaccine. CONCLUSION: We demonstrated that systemic inflammation may occur in subjects who have received the ChAdOx1 nCoV-19 vaccination. Moreover, we proposed immune markers, which may be implicated in the pathogenesis of systemic inflammation following COVID-19 vaccination as potential diagnostic biomarkers.

Association between spirometry pattern, left ventricular diastolic function, and mortality.

BACKGROUND: Spirometric abnormalities have been related to incident heart failure in general population, who generally have preserved left ventricular ejection fraction (LVEF). We aimed to investigate the association between spirometric indices, cardiac functions and clinical outcomes. METHODS: Subjects presenting with exertional dyspnoea and received spirometry and echocardiography were eligible for this study. Forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1)/FVC ratio were measured to define the spirometry patterns: normal (FEV1/FVC ≥ 70%, FVC ≥ 80%), obstructive (FEV1/FVC < 70%, FVC ≥ 80%), restrictive pattern (FEV1/FVC ≥ 70%, FVC < 80%) and mixed (FEV1/FVC < 70%, FVC < 80%). The diastolic dysfunction index (DDi) was the counts of the indicators, including septal e' velocity <7 cm/s, septal E/e' > 15, pulmonary artery systolic pressure > 35 mmHg and left atrial dimension >40 mm. RESULTS: Among a total of 8669 participants (65.8 ± 16.3 years, 56% men), 3739 (43.1%), 829 (9.6%), 3050 (35.2%) and 1051 (12.1%) had normal, obstructive, restrictive and mixed spirometry pattern, respectively. Subjects with restrictive or mixed spirometry pattern had higher DDi and worse long-term survival than those with obstructive or normal ventilation. FVC but not FEV1/FVC was predictive of 5-year mortality, independent of age, sex, renal function, LVEF, DDi, body mass index, and comorbidities (hazard ratio, 95% confidence intervals: .981, .977-.985). Furthermore, there was an inverse nonlinear relationship between FVC and DDi, suggesting the declined FVC may mediate 43% of the prognostic hazard of left ventricular diastolic dysfunction. CONCLUSIONS: The restrictive spirometry pattern or the declined FVC was associated with left ventricular diastolic dysfunction, which aggravated the long-term mortality in the ambulatory dyspnoeic subjects.

Risk stratification in patients with hypertrophic cardiomyopathy: Looking beyond the left side myocardial function.

BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) have heterogeneous outcomes. As risk stratification mostly focuses on left-side myocardial function, we sought to investigate the prognostic value of right ventricular (RV) function in patients with HCM. METHODS: This retrospective cohort study included patients with HCM. Conventional ventricular functional parameters, including left ventricular ejection fraction (LVEF), tricuspid annular plane systolic excursion (TAPSE), and fractional area change were obtained. The longitudinal strain was analyzed using the speckle tracking method. The primary endpoint was defined as a composite of hospitalization for heart failure, sustained ventricular tachycardia, or all-cause death. RESULTS: A total of 56 patients with HCM (aged 58.0 ± 14.9 years, 64.3% male) were included. After a mean follow-up duration of 30.1 ± 17.4 months, primary endpoints developed in 10 (20%) of 50 patients who were treated medically. Patients with cardiovascular events had a more reduced LV thickest segmental strain, worse TAPSE, and more impaired RV free wall strain. After adjusting for age, sex, and LVEF, TAPSE (hazard ratio [HR], 95% confidence intervals [CIs]: 0.24, 0.06-0.93) and RV free wall strain (HR, 95% CIs:1.12, 1.03-1.21) remained independent prognostic predictors. Incorporating either TAPSE or RV free wall strain provides incremental prognostic value to the LV strain alone (net reclassification improvement by 31.4% and 34.1%, respectively, both p < 0.05). CONCLUSION: RV function assessed by TAPSE or RV free wall strain is predictive of subsequent cardiac events, suggesting that a comprehensive evaluation of RV function is useful for risk stratification in patients with HCM.

Left Ventricular Apical Aneurysm in Fabry Disease: Implications for Clinical Significance and Risk Stratification.

Background A previously underrecognized phenotype of left ventricular apical aneurysm (LVAA) has been increasingly identified in Fabry disease. This study explored LVAA's clinical prevalence and its prognostic implications over a long-term follow-up. Methods and Results We retrospectively analyzed 268 consecutive patients with Fabry disease at a tertiary medical center. Patients with increased left ventricular mass index were recognized as having left ventricular hypertrophy (LVH). LVAA was identified using either echocardiography or cardiovascular magnetic resonance imaging. Two patients with ischemic LVAA were excluded. The primary end point was a composite of cardiovascular events, including heart failure hospitalization, sustained ventricular tachycardia, ischemic stroke, and all-cause mortality. Of 266 enrolled patients, 105 (39.5%) had LVH (age 58.5±11.9 years, 48.6% men), and 11 (10.5%) had LVAA. Over 49.3±34.8 months of follow-up, 25 patients with LVH experienced composite events, including 9 heart failure hospitalizations, 4 sustained ventricular tachycardia, 6 ischemic strokes, and 15 mortalities. In patients with LVH, those with LVAA had a significantly higher risk of composite events and lower event-free survival than those without LVAA (8 [72.7%] versus 17 [18.1%], log-rank P<0.001). LVAA was independently associated with an increased risk of composite events (hazard ratio, 3.59 [95% CI, 1.30-9.91]; P=0.01) after adjusting for age, sex, advanced heart failure, renal function, dyslipidemia, atrial fibrillation, left ventricular ejection fraction, left ventricular diastolic function, and left ventricular mass index. Conclusions LVAA is present in approximately 10% of patients with Fabry disease and LVH. It is associated with an increased risk of adverse cardiovascular events and may necessitate aggressive treatment.

TIMP-1 in the prognosis of patients who underwent coronary artery bypass surgery: a 12-year follow-up study.

Introduction: Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have been linked to clinical outcomes in patients with coronary artery disease (CAD). However, the prognostic value of TIMP-1 in patients with CAD who underwent coronary artery bypass grafting (CABG) has not been elucidated. We aimed to investigate the correlations of TIMP-1 with high-sensitivity C-reactive protein (hs-CRP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in the long-term prognosis of consecutive patients who underwent CABG. Methods: A total of 234 patients (age: 70.4 ± 10.5 years, 84.6% men) with CAD who underwent CABG were prospectively enrolled. Preoperative levels of MMPs, TIMP-1, hs-CRP, and NT-proBNP were recorded. Major adverse cardiovascular events (MACE) were defined as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death. Results: During a median follow-up of 12.1 years, 120 deaths were recorded. The deceased were older, had more manifest acute coronary syndrome (ACS), a lower left ventricular ejection fraction (LVEF), and an estimated glomerular filtration rate (eGFR), but significantly higher MMP13, TIMP-1, hs-CRP, and NT-proBNP compared with the survivors. After adjusting for age, sex, manifest ACS, eGFR, LVEF, total cholesterol, and triglycerides, TIMP-1 (hazard ratio and 95% confidence intervals per SD: 1.506, 1.183-1.917), hs-CRP (1.349, 1.183-1.561), and NT-ProBNP (1.707, 1.326-2.199) were all independently associated with all-cause mortality. The mediation analysis revealed that the mortality risks of TIMP-1 were partially mediated by NT-proBNP (62.2%) and hs-CRP (25.3%). The associations of TIMP-1 with MACE were partially mediated by NT-proBNP (54.4%) but not hs-CRP. Conclusions: TIMP-1 was an independent predictor of long-term outcomes after CABG, with possible roles in subclinical inflammation and postoperative cardiac remodeling.

Cardiomyocyte Globotriaosylceramide Accumulation in Adult Male Patients with Fabry Disease and IVS4 + 919G>A GLA Mutation is Progressive with Age and Correlates with Left Ventricular Hypertrophy and Reduced Left Ventricular Ejection Fraction.

Background: While cardiovascular complications are the most common cause of mortality in Fabry disease, the relationship between globotriaosylceramide (GL-3) accumulation, the hallmark of Fabry cardiomyopathy, and cardiac hypertrophy has not been fully elucidated. Methods: We developed unbiased stereology protocols to quantify the ultrastrcture of Fabry cardiomyopathy. Endomyocardial biopsies from 10 adult male enzyme replacement therapy naïve Fabry patients with IVS4 + 919G>A GLA mutation were studied. The findings were correlated with cardiac MRI and clinical data. Results: Ultrastructural parameters showed significant relationships with key imaging and clinical and functional variables. Average cardiomyocyte volume and GL-3 volume per cardiomyocyte were progressively increased with age. Eighty-four percent of left ventricular mass index (LVMI) variability was explained by cardiomyocyte nuclear volume, age and plasma globotriaosylsphingosine with cardiomyocyte nuclear volume being the only independent predictor of LVMI. Septal thickness was directly and left ventricular ejection fraction (LVEF) was inversely correlated with cardiomyocyte GL-3 accumulation. Sixty-five percent of left ventricular ejection fraction (LVEF) variability was explained by cardiomyocyte GL3 volume, serum α-galactosidase-A activity and age with cardiomyocyte GL3 volume being the only independent predictor of LVEF. Residual α-galactosidase-A activity was directly correlated with myocardial microvasculature density. Conclusions: The unbiased stereological methods introduced in this study unraveled novel relationships between cardiomyocyte structure and important imaging and clinical parameters. These novel tools can help better understand Fabry cardiomyopathy pathophysiology.

Prompt diagnosis of a wild-type transthyretin cardiac amyloidosis: Role of multimodality imaging.

Amyloidosis cardiomyopathy is a rare and underdiagnosed disease characterized by amyloid fibril deposition in the myocardium. The diagnosis of cardiac amyloidosis is often delayed due to a lack of awareness and the necessity of biopsy to confirm the diagnosis. Recent advances in cardiovascular imaging modalities have enhanced earlier recognition of this disease. A 66-year-old man experiences progressive shortness of breath for two weeks. Laboratory testing was significant for an elevation of cardiac biomarkers (creatine kinase: 522 U/L, troponin I: 0.10 ng/mL) and NT-pro-BNP (5074 pg/mL). He was diagnosed with acute coronary syndrome and received stent deployment. Nonetheless, progressive shortness of breath recurred in 2 months. Transthoracic echocardiography (TTE) demonstrated an increased left ventricular (LV) wall thickness with apical sparing. Cardiac magnetic resonance (CMR) imaging demonstrated high native T1 value, increased extracellular volume fraction as well as diffused subendocardial late gadolinium enhancement. Technetium-99m pyrophosphate (99mTc-PYP) scintigraphy, endomyocardial biopsy (EMB), and the genetic study confirmed the diagnosis of wild-type transthyretin amyloidosis (ATTRwt). The nonspecific clinical manifestations, lack of diagnostic biomarkers, and the rarity of systemic amyloidosis usually lead to delayed diagnosis and treatment. Our objective is to emphasize the role of multimodalities imaging in reducing delays to the diagnosis of cardiac amyloidosis.

The fibrosis-4 score is associated with long-term mortality in different phenotypes of acute heart failure.

BACKGROUND: Fibrosis-4 score (FIB4) was a non-invasive surrogate to estimate the amount of liver scarring in chronic hepatitis. Considering the presence of increased central venous pressure and congestive hepatopathy in patients with decompensated heart failure, we therefore investigated the prognostic values of FIB4 in acute heart failure (AHF) patients. METHOD: Patients hospitalised primarily for HF were drawn from an intramural registry. FIB4 was calculated according to age, aspartate aminotransferase, alanine aminotransferase and platelet count. All-cause mortality up to 5 years after discharge was obtained by linking to the national death registry. RESULTS: Among a total of 1854 participants, 940 patients died during a mean follow-up of 28.3 ± 21.8 months. FIB4 score was related to mortality and the composite of cardiovascular death or HF rehospitalisation, independent of age, sex, left ventricular ejection fraction, left atrial dimension, sodium and haemoglobin levels, estimated glomerular filtration rate, comorbidities, and medications [hazard ratio and 95% confidence interval of mortality: 1.009 (1.002-1.015), and the composite of cardiovascular death or HF hospitalisation: 1.020 (1.010-1.031)]. The prognostic value of FIB4 was predominantly in the subjects with heart failure and preserved or mildly reduced ejection fraction (HFpEF and HFmrEF), or coronary artery disease (CAD) than the counterparts [interaction p-value <0.001, and 0.004, respectively]. CONCLUSIONS: FIB4 was an independent predictor of survival in AHF patients, irrespective of the phenotypes of HF. The higher predictive value of mortality of FIB4 was observed in the subjects with HFpEF, HFmrEF or CAD.

Clinical recommendations to diagnose and monitor patients with transthyretin amyloid cardiomyopathy in Asia.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a debilitating and life-threatening condition with a heterogeneous clinical presentation. Recent guidelines from the United States and Europe have been published to guide clinical practice and to facilitate management conformity by covering current diagnostic and treatment strategies for patients with ATTR-CM. These guidelines highlight the importance of an early diagnosis to optimize therapeutic outcomes, specifying the use of tests and imaging techniques to allow accurate, noninvasive diagnosis of ATTR-CM. However, as regional practice variations across Asia may limit access to healthcare, availability of specific tests, and expertise in assessing diagnostic images, there is an ongoing need to provide an Asian perspective on these clinical guidelines. This review article provides practical recommendations for the diagnosis and monitoring of patients with ATTR-CM in Asia, highlighting the need for additional guidelines to support a broad and diverse population, consider differing healthcare systems and diagnostic testing availability, and provide a flexible yet robust algorithm.