Infiltrative Cardiomyopathy Research Articles

Prediction of Cardiac ATTR Depletion by NI006 (ALXN2220) Using Mechanistic PK/PD Modeling.

NI006 (aka ALXN2220) is a therapeutic antibody candidate in phase III clinical development for the depletion of amyloid transthyretin (ATTR) in patients with ATTR cardiomyopathy, an infiltrative cardiomyopathy leading to increased left ventricular wall thickness (LVWT). The mode-of-action consists in removal of disease-causing amyloid accumulations by activating phagocytic immune cells, a mechanism without precedent in cardiology. To select a safe and potentially efficacious dose range and treatment duration for a combined first-in-human and proof-of-concept clinical phase Ib study, we developed a mechanistic pharmacokinetic and pharmacodynamic (PK/PD) model that can predict NI006 exposure, its effects on cardiac amyloid load and on LWVT, which is a predictor of heart failure in this disease. The PK/PD model predictions supported 0.3 mg/kg monthly dosing as a safe starting dose and identified 10-60 mg/kg monthly as the potentially efficacious dose range with substantial and dose dependent cardiac amyloid burden reduction within 4 months for 60 mg/kg and 10 months for 10 mg/kg. These predictions were in good agreement with the observed primary results of the clinical phase Ib study where amyloid burden was measured by imaging. This novel translational PK/PD model provided important predictions to guide the design of the phase Ib study of NI006, indicating the value of this approach to integrate preclinical results into clinical trial design and increase translational success.

Is LVH a must in an amyloid heart?

Abstract Background Transthyretin amyloidosis (ATTR), an infiltrative cardiomyopathy, is characterized by the infiltration of transthyretin-derived amyloid fibrils into the cardiac extracellular space, which causes morphological and functional heart damage. Because of the vast range of symptoms that can accompany ATTR cardiac amyloidosis, the illness remains unknown. However, misdiagnosis or delayed diagnosis due to inconsistencies between clinical findings and the severity of the underlying disease hampers treatment methods. Aim and objectives This article investigates the intricate relationship between ATTR amyloidosis pathogenesis and clinical signs to understand better the challenges and advancements in early discovery, treatment, and prognosis of this concealed sickness. Methods & Results Between November 2022 and April 2024, we conducted a prospective analysis on a cohort of 71 patients diagnosed with ATTR cardiac amyloidosis utilizing PYP imaging at our institution (Al Hada Armed Force Hospital, Taif, Saudi Arabia). The Medical Ethics Review Committee of the hospital accepted this project (2023-720). During our study, we faced two cases without LVH and both cases have grade II-III cardiac uptake. 1st case A 66-year-old male patient who is a known case of ischemic cardiomyopathy with EF 35% since 2018, he underwent PCI in 2018. The patient is following the cardio clinic since 2018 and on every visit he was asymptomatic, The Patient in 2021 experienced new shortness of breath within six minutes’ walk distance less than 400 meters. The patient experienced erectile dysfunction and underwent intervention for his carpal tunnel syndrome. ECG showed old Q in anterior leads. Echo showed the same EF 35% and old wall motion abnormalities. Diagnostic coronary angiography showed patent stents and no residual ischemia. When we revised his old echo study that was done in 2017, we found EF 55%, concentric LVH. PYP bone scintigraphy was decided and showed grade II-III cardiac uptake. 2nd case A 53-year-old hypothyroid female patient and she has metastatic left breast cancer. During her workup bone scan, grade III cardiac uptake was accidentally discovered using an HMDP isotope. The patient was referred to the cardio clinic where the patient denied any cardiac or non-cardiac symptoms. All her labs, ECG and Echo were within normal range. CMR showed diffuse subendocardial LGE suggestive of infiltrative disease. Conclusion Based on unique pathological features of CA that would present as morphological LVH with /without ECG evidence of LVH. We hypothesized that LVH would occur in the later stages of the disease or may be decreased due to other pathology as coronary artery disease. Clinical suspicion remains the cornerstone for early diagnosis and workup.

P144 PHENOTYPIC CHARACTERISATION OF HEART FAILURE WITH PRESERVED EJECTION FRACTION ACCORDING TO BODY MASS INDEX: SUBANALYSIS OF THE ARGENTINE ARFEY-PRESER REGISTRY

Background: Nutritional status, characterised by body mass index (BMI), may influence therapeutic decisions in heart failure with preserved ejection fraction (HFpEF). The objectives of this study were to identify clinical and echocardiographic characteristics associated with nutritional status and to analyse therapeutic strategies in HFpEF patients in Argentina. Materials and Methods: This prospective, multicentre observational registry enrolled outpatients or those discharged from hospitals, with prior informed consent. The study spanned from December 2022 to February 2024. Inclusion criteria were: 1) presence of current signs and symptoms, LVEF ≥50%, 2) structural heart disease with LVH, LAE, or average E/e’ ≥15 on Doppler, 3) elevated natriuretic peptides: sinus rhythm: NTproBNP >125 pg/ml or BNP >35 pg/ml; Atrial fibrillation/flutter: NTproBNP >375 pg/ml or BNP >105 pg/ml; and 5) commitment to 6-month and 1-year follow-ups. Exclusion criteria comprised: 1) acute coronary syndrome, 2) coronary artery bypass grafting, or valve replacement within the preceding 3 months, 3) confirmed infiltrative or hypertrophic cardiomyopathy, severe valvular disease, 4) severe illness with <1-year prognosis, and chronic renal failure on permanent dialysis. Results: A total of 449 patients were enrolled, with 440 having available BMI data for this analysis. Patient enrolment was consistent across centres and nationwide. BMI analysis revealed 0.7% undernutrition, 16.6% normal weight, 32% overweight, and 50.7% obesity. In Figure1 showed the analysis of clinical, laboratory, echocardiographic, and HF severity variables according to BMI. Significant differences were found in treatment, with lower use of RAS inhibitors and beta-blockers in non-normal weight patients compared to those with overweight and obesity. Conclusions: For a similar HFpEF severity profile, the phenotype according to BMI suggests different clinical characteristics. Underweight/normal weight patients were older, with more LAE and pulmonary hypertension, and fewer risk factors. Obesity was present in half of the cases, characterised by younger patients with a high burden of cardiovascular risk factors. This impacts the use of certain heart failure medications.

Hot Hearts on Bone Scintigraphy Are Not All Amyloidosis: Hyperoxaluria-Associated Cardiomyopathy.

A 54-year-old woman with a history of end-stage renal disease was found to have infiltrative cardiomyopathy by echocardiography. 99mTc-pyrophosphate (99mTc-PYP) scintigraphy was positive with a remarkable myocardial uptake. Gene test found a mutation of AGXT, confirming a final diagnosis of primary hyperoxaluria. Radiotracer uptake was due to high myocardial oxalate deposition. This case illustrates false positivity of the 99mTc-PYP scan caused by hyperoxaluria-associated cardiomyopathy, which raises awareness for other conditions apart from amyloid cardiomyopathy.

Role of Cardiac Magnetic Resonance in Inflammatory and Infiltrative Cardiomyopathies: A Narrative Review.

Cardiac magnetic resonance (CMR) has acquired a pivotal role in modern cardiology. It represents the gold standard for biventricular volume and systolic function assessment. Moreover, CMR allows for non-invasive myocardial tissue evaluation, highlighting tissue edema, fibrosis, fibro-fatty infiltration and iron overload. This manuscript aims to review the impact of CMR in the main inflammatory and infiltrative cardiomyopathies, providing details on specific imaging patterns and insights regarding the most relevant trials in the setting.

Epidemiology, diagnosis, and management of cardiac amyloidosis.

Cardiac amyloidosis (CA) is an infiltrative restrictive cardiomyopathy caused by the deposition of amyloid fibrils in the myocardium. It manifests in two primary subtypes: transthyretin cardiac amyloidosis (ATTR) and immunoglobulin light chain cardiac amyloidosis (AL). ATTR is further classified into wild-type and hereditary based on transthyretin gene mutation. Advances in diagnostics and therapeutics have transformed CA from a rare and untreatable condition to a more prevalent and manageable disease. Noninvasive diagnostic tools such as electrocardiography, echocardiography, and cardiac magnetic resonance can raise suspicion for CA; bone scintigraphy can non-invasively confirm ATTR, while AL necessitates histological confirmation. The severity of ATTR and AL can be assessed through serum biomarker-based staging. Treatment approaches differ, ranging from silencing or stabilizing transthyretin and degrading amyloid fibrils in ATTR to employing anti-plasma cell therapies and autologous stem cell transplantation in AL.

Breaking Barriers: Nuclear Cardiology’s Frontier in Diagnosing Infiltrative Cardiomyopathies in Bangladesh

Breaking Barriers: Nuclear Cardiology’s Frontier in Diagnosing Infiltrative Cardiomyopathies in Bangladesh

Fatal Immune Checkpoint Inhibitor-associated Myocarditis Mimicking Infiltrative Cardiomyopathy in a 54-year-old Woman with Metastatic Melanoma

Introduction: Immune checkpoint inhibitors (ICI) have significantly improved cancer treatment outcomes, but cardiovascular complications such as ICI-associated myocarditis are a major concern. Diagnosing myocarditis requires integrating biomarkers, electrocardiogram (EKG), cardiac imaging, and endomyocardial biopsy. We present a case illustrating these diagnostic challenges, involving a female patient treated with pembrolizumab who developed fatal acute myocarditis mimicking infiltrative cardiomyopathy. Case report: A 54-year-old woman with mucosal melanoma, treated with pembrolizumab, was hospitalized in May 2023 due to dyspnea and elevated troponin levels. Initial cardiac workups were normal, but subsequent tests revealed borderline cardiac magnetic resonance imaging findings. In late May 2023, the patient was admitted with worsening dyspnea, elevated NT-pro-BNP, and severe hyperlactatemia. Imaging and endomyocardial biopsy confirmed acute myocarditis with atypical presentation, mimicking infiltrative cardiomyopathy. Despite aggressive immunosuppressive therapy, the patient’s condition deteriorated, resulting in cardiogenic shock and death seven days post-admission. Conclusion: This case underscores the diagnostic and management challenges of ICI-associated myocarditis, particularly with atypical presentations. It highlights the need for vigilant, comprehensive monitoring and further research to improve diagnostic and therapeutic strategies for managing these severe side effects in patients undergoing ICI therapy.

The Role of T2 Mapping in Cardiac Amyloidosis.

Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy divided into two types: light-chain (LA) and transthyretin (ATTR) CA. Cardiac magnetic resonance (CMR) has emerged as an important diagnostic tool in CA. While late gadolinium enhancement (LGE), T1 mapping and extracellular volume (ECV) have a consolidate role in the assessment of CA, T2 mapping has been less often evaluated. We aimed to test the value of T2 mapping in the evaluation of CA. This study recruited 70 patients with CA (51 ATTR, 19 AL). All the subjects underwent 1.5 T CMR with T1 and T2 mapping and cine and LGE imaging. Their QALE scores were evaluated. The myocardial T2 values were significantly (p < 0.001) increased in both types of CA compared to the controls. In the AL-CA group, increased T2 values were associated with a higher QALE score. The myocardial native T1 values and ECV were significantly (p < 0.001) higher in the CA patients than in the healthy subjects. Left ventricular (LV) mass, QALE score and ECV were higher in ATTR amyloidosis compared with AL amyloidosis, while the LV ejection fraction was lower (p < 0.001). These results support the concept of the presence of myocardial edema in CA. Therefore, a CMR evaluation including not only myocardial T1 imaging but also myocardial T2 imaging allows for more comprehensive tissue characterization in CA.

MULTIDISCIPLINARY APPROACH TO A DIFFICULT CASE OF ACUTE HEART FAILURE DUE TO POSSIBILE ISOLATED CARDIAC SARCOIDOSIS

Abstract Background Cardiac sarcoidosis (CS) is a rare, infiltrative cardiomyopathy that results from granulomatous inflammation affecting the heart with high morbidity and mortality. It is usually associated with a systemic (i.e. pulmonary) involvement, but lone heart involvement has been described. Even with extensive multidisciplinary evaluation making a firm diagnosis is difficult, especially in case of isolated CS where the endomyocardial biopsy (EBM) diagnostic yield is low (20–30%). Case Description A 71–year–old patient, heavy smoker with no previously known diseases, was admitted with a 3–month history of dyspnea. On admission he showed typical features of heart failure with reduced ejection fraction (HFrEF). A coronary angiography excluded coronary artery disease, while echocardiography (TTE), cardiac magnetic resonance (CMR), and positron emission tomography (FDG–PET) showed a pattern consistent with a non–ischemic dilated cardiomyopathy with reduction in systolic function, and signs of active inflammation (highly suspected CS). Two electroanatomic mapping driven EBM were made but no clear histological signs of CS (i.e., granulomatous inflammation) were detected. The patient was treated with corticosteroids and HFrEF optimal medical therapy (sacubitril/valsartan, mineralocorticoid receptor antagonists, beta–blockers, dapagliflozin) and a temporary wearable defibrillator (LifeVest) was applied. At 2–month follow–up, despite a moderate improvement in the systolic function and HF symptoms, after a multidisciplinary discussion, considering the extensive left ventricle scar, inflammatory involvement, and the presence of multiple non–sustained ventricular tachycardia, a permanent cardioverter–defibrillator (ICD) was implanted. Conclusion This case highlights how, even with (repeated) extensive multidisciplinary evaluation (TTE, CRM, FGD–PET, EBM), a definitive diagnosis of isolated CS often remains presumptive. The presence of an experienced cardiomyopathy team (HF specialists, cardiac imager, electrophysiologists, internal medicine doctor) can help in the diagnostic–therapeutic management of these patients with inflammatory heart disease.

Arrhythmias and amyloidosis

Cardiac amyloidosis is an infiltrative cardiomyopathy characterized by the extracellular deposition of amyloid fibrils within the myocardium. Beyond heart failure, patients with cardiac amyloidosis commonly present with arrhythmias and conduction system disorders. Atrial fibrillation is observed in up to 80% of patients at the time of diagnosis, with patients typically maintaining normal heart rates due to concurrent atrioventricular nodal disease. The thromboembolic risk is particularly high in patients with cardiac amyloidosis, and left atrial thrombi have been observed even in the absence of atrial fibrillation. Conduction system diseases are also highly prevalent, often necessitating permanent pacemaker implantation. The use of implantable defibrillators in this population remains controversial. This overview of published data and therapeutic strategies related to arrhythmias and conduction system disorders aims to assist readers in decision-making in complex clinical scenarios.

Acute Coronary Syndrome (ACS) with ST-Segment Elevation Revealing Cardiac Amyloidosis: A Case Report and Literature Review

Cardiac Amyloidosis (CA) is an infiltrative cardiomyopathy characterized by the accumulation of fibrillar proteins in the myocardium. The deposition of these proteins disrupts the structure and function of the heart, leading to thickened walls, increased myocardial mass, diastolic dysfunction, and altered myocardial contraction, ultimately causing progressive heart failure. We report the case of a 65-year-old patient, S.L., admitted to our service with Acute Coronary Syndrome (ACS) with a posterior extended ST-segment elevation, Killip class I, semi-recent. She is hypertensive and diabetic; she previously underwent surgery for chronic constrictive pericarditis, presumed to be of tuberculous origin, and was treated accordingly. The echocardiogram revealed a hypokinetic left ventricle (LV), predominantly affecting the inferior, inferoseptal, and apical walls. The left and right atria were not dilated, and both ventricles were of normal size. Coronary angiography showed no significant anomalies. Cardiac MRI supported a diagnosis of localized amyloidosis. Through this case, we explore the various clinical forms of CA, referencing existing literature.

Diagnosis and Management of Cardiac Sarcoidosis: A Scientific Statement From the American Heart Association.

Cardiac sarcoidosis is an infiltrative cardiomyopathy that results from granulomatous inflammation of the myocardium and may present with high-grade conduction disease, ventricular arrhythmias, and right or left ventricular dysfunction. Over the past several decades, the prevalence of cardiac sarcoidosis has increased. Definitive histological confirmation is often not possible, so clinicians frequently face uncertainty about the accuracy of diagnosis. Hence, the likelihood of cardiac sarcoidosis should be thought of as a continuum (definite, highly probable, probable, possible, low probability, unlikely) rather than in a binary fashion. Treatment should be initiated in individuals with clinical manifestations and active inflammation in a tiered approach, with corticosteroids as first-line treatment. The lack of randomized clinical trials in cardiac sarcoidosis has led to treatment decisions based on cohort studies and consensus opinions, with substantial variation observed across centers. This scientific statement is intended to guide clinical practice and to facilitate management conformity by providing a framework for the diagnosis and management of cardiac sarcoidosis.

How Artificial Intelligence Can Enhance the Diagnosis of Cardiac Amyloidosis: A Review of Recent Advances and Challenges.

Cardiac amyloidosis (CA) is an underdiagnosed form of infiltrative cardiomyopathy caused by abnormal amyloid fibrils deposited extracellularly in the myocardium and cardiac structures. There can be high variability in its clinical manifestations, and diagnosing CA requires expertise and often thorough evaluation; as such, the diagnosis of CA can be challenging and is often delayed. The application of artificial intelligence (AI) to different diagnostic modalities is rapidly expanding and transforming cardiovascular medicine. Advanced AI methods such as deep-learning convolutional neural networks (CNNs) may enhance the diagnostic process for CA by identifying patients at higher risk and potentially expediting the diagnosis of CA. In this review, we summarize the current state of AI applications to different diagnostic modalities used for the evaluation of CA, including their diagnostic and prognostic potential, and current challenges and limitations.

Kiosk 8Q-FA-02 - Fatal Immune-mediated Myocarditis Mimicking Infiltrative Cardiomyopathy in a 54-year-old Woman with Metastatic Melanoma: A Case Report

Kiosk 8Q-FA-02 - Fatal Immune-mediated Myocarditis Mimicking Infiltrative Cardiomyopathy in a 54-year-old Woman with Metastatic Melanoma: A Case Report

Albuminuria in transthyretin cardiac amyloidosis: Prevalence, progression and prognostic importance.

Transthyretin cardiac amyloidosis (ATTR-CA) is an infiltrative cardiomyopathy that commonly presents with concomitant chronic kidney disease. Albuminuria is common in heart failure and associated with worse outcomes, but its prevalence and relationship to outcome in ATTR-CA remains unclear. A total of 1181 patients with ATTR-CA were studied (mean age 78.1 ± 7.9 years; 1022 [86.5%] male; median estimated glomerular filtration rate 59 ml/min/1.73m2 [interquartile range: 47-74]). Albuminuria was present in 563 (47.7%) patients (499 [88.6%] with microalbuminuria and 64 [11.4%] with macroalbuminuria). Patients with albuminuria had a more severe cardiac phenotype evidenced by higher serum cardiac biomarkers (median N-terminal pro-B-type natriuretic peptide [NT-proBNP]: 4027 ng/L [2173-6889] vs. 1851 ng/L [997-3209], p < 0.001; median troponin T: 69 ng/L [46-101] vs. 48 ng/L [34-68], p < 0.001) and worse echocardiographic indices of systolic (longitudinal strain: -10.0 ± 3.6% vs. -11.6 ± 3.8%, p < 0.001) and diastolic function (E/e': 17.5 ± 6.4 vs. 16.4 ± 6.7, p < 0.001) than those with a normal urinary albumin to creatinine ratio (UACR). Microalbuminuria and macroalbuminuria were independently associated with mortality in the overall population (hazard ratio [HR] 1.47, 95% confidence interval [CI] 1.13-1.92, p = 0.005 and HR 1.87, 95% CI 1.15-3.05, p = 0.012, respectively). In a subgroup of patients (n = 349) without concomitant hypertension, diabetes mellitus or chronic kidney disease, albuminuria was also associated with mortality (HR 2.98, 95% CI 1.72-5.17, p < 0.001). At 12 months, 330 patients had a repeat UACR measurement; those in whom UACR increased by 30% or more (n = 148, 44.8%) had an increased risk of mortality (HR 1.84, 95% CI 1.06-3.19, p = 0.030). Albuminuria is common in patients with ATTR-CA, and more prevalent in those with a more severe cardiac phenotype. Albuminuria at diagnosis and a significant increase in UACR during follow-up are associated with mortality.

Prevalence and incidence of diastolic dysfunction in new-onset atrial fibrillation: implications for clinical and preclinical HFpEF

Abstract Background Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) are closely associated diseases that frequently coexist. However, due to the overlapping symptoms, the diagnosis of HFpEF can be overlooked with symptoms being attributed to AF. Purpose We aimed to investigate the prevalence of diastolic dysfunction (DD) in patients with new-onset AF compared to sinus rhythm (SR), study changes in diastolic function parameters over time in the two groups and compare the incidence of DD at follow-up. Methods Adults with new diagnosis of AF and adults in SR were identified. Patients with previous cardiac surgeries, congenital heart disease, hypertrophic or infiltrative cardiomyopathy, primary mitral disease, left-sided valve disease, low ejection fraction, enlarged left ventricle, or with no 6-month follow-up echocardiogram were excluded. Diastolic function was assessed through 4 components: mitral medial e’ &amp;lt;0.07 m/sec, mitral medial E/e’ &amp;gt;15 in SR and &amp;gt;11 in AF, TR velocity &amp;gt;2.80 m/sec, and left atrial volume index &amp;gt;34 ml/m2, with severe DD (SDD) defined by ≥3/4 findings and moderate DD (MDD) by ≥2/4 abnormal diastolic function parameters. Annualized changes were calculated as the difference between follow-up and baseline values divided by years in between. In a secondary analysis, patients with new-onset AF were propensity score-matched to patients with SR in a 3:1 ratio based on age, sex, body mass index, and comorbidities. Results Overall, 1,747 patients with incident AF (median age 67 years; 34% females) and 29,623 in SR (median age 59 years; 51% females) were included. New-onset AF was independently associated with the presence of SDD vs SR (8% vs 2%) and MDD (25% vs 11%, p&amp;lt;.001 for both in adjusted analysis). Over median follow-up of 3.2 (IQR 1.6-5.8) years, annualized severity progression in each of the 4 diastolic function parameters was greater in the AF group (p&amp;lt;.001 for all), Table. The incidence rates of SDD and MDD were 3.7 and 8.8 per 100-person year, respectively, in AF versus 1.1 and 3.6 per 100-person years, respectively, in SR (p&amp;lt;.001 for both at univariate and multivariable analysis), Figure. Results were similar in the propensity-score matched analysis. Conclusions Patients with new-onset AF more commonly have moderate or severe diastolic dysfunction that indicates the presence of potentially overlooked clinical HFpEF (when symptoms exist) or preclinical HFpEF (when symptoms are absent) compared to patients in SR. In long-term follow-up, patients with AF display accelerated progression in DD; suggesting that therapies to prevent progression to symptomatic HFpEF may be highest value in this patient population.

Is a change of the current echocardiographic red flag for left ventricular wall thickness useful in cardiac amyloidosis screening?

Abstract Background Cardiac amyloidosis (CA) is a serious and progressive infiltrative cardiomyopathy caused by the extracellular deposition of amyloid fibrils in the myocardium. As new disease-modifying therapies are increasingly emerging, prompt and specific diagnosis is fundamental to avoid treatment delay. Echocardiography is the most often used first-line imaging tool for amyloidosis screening. Left ventricular (LV) wall thickness ≥12 mm and age ≥65 years are major criteria for the suspicion of CA. However, it is very likely that many patients, especially in the early stages of the disease, will not be detected. Reducing the diagnostic wall thickness threshold will certainly increase the sensitivity of the amyloidosis screening. It is to be feared, however, that reduction of the cut-off will lead to a large number of patients being unnecessarily subjected to further testing, and substantially increase costs. Objective We investigated the distribution of interventricular septum thickness (IVS) in patients referred for routine echocardiography with the aim of establishing a wall thickness cut-off value that is assumed to be suitable for targeted amyloidosis screening. Methods We retrospectively analysed the echocardiographic reports from August 2021 to December 2021 at our department. Individual IVS values were documented and categorised. This was to give an idea of how many patients were potentially eligible for further amyloidosis screening solely due to changes in the echocardiographic IVS cut-off value. Results 1.007 echocardiographic reports were analysed. Of these, 900 included a valid IVS value, while 107 (mainly exclusions of pericardial effusion) did not. From IVS ≥15 mm (5.4%), to ≥14 mm (10.0%), to ≥13 mm (18.6%), to ≥12 mm (32.0%) an increase in patient number was recorded (Figure 1). With regard to CA diagnosis, it can be assumed that systematic screening of patients with IVS ≥12 mm will certainly result in increasing sensitivity but in turn decreasing specificity. On the basis of the patient number within each IVS category we conclude that amyloidosis screening of patients with an IVS ≥13 mm is feasible and reasonable. Conclusion We herein conclude that an IVS ≥13 mm should result in targeted amyloidosis screening. In case of IVS &amp;lt;13 mm the use of further red flags is recommended to avoid unnecessary amyloidosis screening and disproportionate increase in costs.

Advanced echocardiographic assessment in wild-type and hereditary transthyretin cardiac amyloidosis: the role of myocardial work and left atrial strain

Abstract Introduction Transthyretin cardiac amyloidosis (ATTR-CA) is a progressive infiltrative cardiomyopathy caused by extracellular deposition of insoluble transthyretin (TTR) amyloid fibrils in the myocardium. ATTR-CA can be classified as wild type ATTR-CA (ATTRwt-CA), caused by age-related misfolding of TTR, and hereditary ATTR-CA (ATTRv-CA), an autosomal dominant disease in which gene mutations lead to changes in TTR protein. Speckle tracking echocardiography and myocardial work (MW) analysis can better characterize left ventricular and left atrial (LA) function in ATTRwt-CA and in ATTRv-CA. Aims to investigate differences in myocardial work and left atrial strain parameters between patients affected by ATTRwt-CA and patients affected by ATTRv-CA. Material and methods 40 male patients affected by ATTR-CA were prospectively enrolled, distinguishing between 20 patients with ATTRwt-CA (76 ± 7 yrs) and 20 patients with ATTRv-CA (74 ± 6 yrs) (1 pts with Val30Met mutation, 6 pts with Val122Ile mutation; 8 pts with Glu89Gln mutation; 5 pts with Phe64Leu mutation). All underwent a transthoracic echcoardiogram to calculate global longitudinal strain (GLS), MW parameters and LA strain. Results No difference was found between the two groups (ATTRwt-CA vs ATTRv-CA) for what regards age (76 ± 7 vs 74 ± 6 yrs, p = 0,06), BMI (27,2 ± 2,2 vs 26,6 kg/mq; p = 0,3), BSA (1,8 ± 0,2 vs 1,7 ± 0,1 mq; p = 0,1) and left ventricle mass index (LVMi) (183,41 ± 45,2 vs 148,5 ± 47,3 g/mq; p = 0,07). In ATTRwt-CA patients, ejection fraction (EF) is lower, but without any statistical significance (50 ± 6,9 vs 54 ± 6,4 %, p = 0,06). On the other hand, in ATTRwt-CA patients GLS is significantly higher than in ATTRv-CA patients (-9,8 ± 3,2 vs -15,0 ± 2,5 %; p &amp;lt; 0,0001). Global work index (GWI) (853,6 ± 367,6 vs 1431,6 ± 318,3 mmHg%; p &amp;lt; 0,0001), global constructive work (GCW) (1169 ± 303 vs 1726,5 ± 310,3 mmHg %; p &amp;lt; 0,0001) and global work efficiency (GWE) (83,2 ± 9,4 vs 89 ± 5,3 %; p = 0,04) are significantly reduced in ATTRwt-CA in comparison with ATTRv-CA. For what regards atrial function, in ATTwt-CA patients LA reservoir (9,7 ± 3,7 vs 17,6 ± 7,5 %; p = 0,004) and LA ejection fraction (LAFE) (28,9 ± 13,6 vs 46,2 ± 8,9; p = 0,02) are reduced, while LA booster is higher (-2,5 ± 3,1 vs -10 ± 4,7 %; p &amp;lt; 0, 0001). Conclusion In patients with ATTR-CA advanced echocardiographic assessment can better differentiate left atrial and left ventricular involvement in ATTRwt-CA versus ATTRv-CA.TablesGraphs

The electrophysiological substrate of biopsy-proven cardiac amyloidosis

Abstract Background Cardiac amyloidoses (CA) are an increasingly recognized group of infiltrative cardiomyopathies associated with high risk of major adverse cardiac events. Endomyocardial biopsy (EMB) may be required to differentiate the amyloid type (mainly, Immunoglobulin light chain [AL] versus transthyretin-related [ATTR]) in some cases. Purpose The aim of this study was to provide the first description of the right ventricular (RV) electroanatomical substrate of CA, and assess its association with EMB findings and clinical outcomes. Methods We enrolled ten consecutive patients undergoing EMB for suspected CA (median age, 68[63-77]; male, 50%) in a monocentric, observational, retrospective study. All patients had a clinical diagnosis of CA, but a diagnosis of CA type was hampered by the presence of inconclusive or discordant laboratory-imaging findings (abnormal serum free light chain assay and positive bone scintigraphy, n=5; ambiguous imaging results, n=4; abnormal serum free light chain assay and TTR gene mutation, n=1). Therefore, each patient underwent RV high-density electroanatomical voltage mapping (EVM) and EMB. The primary outcome was death or hospitalization at 1-year follow-up. We recorded electrogram features at EMB sampling sites and in the overall RV, and explored their correlations with histopathological findings and primary outcomes events. Results A final EMB-proven diagnosis of AL or ATTR CA was formulated in 6 and 4 patients, respectively. Electrogram amplitudes in the bipolar and unipolar configurations averaged 1.58±0.65 mV, and 5.38±1.41 in the overall RV. We found a significant inverse correlation between unipolar electrogram amplitude and amyloid burden at EMB (p&amp;lt;0.001); the unipolar voltage cutoff that best identified regions with &amp;gt;15% amyloid tissue infiltration according to Youden index was 9.1 mV (sensitivity, 43%; specificity, 100%; accuracy, 77%). At 1-year follow-up, 6 patients (60%) experienced a primary outcome event. Compared to subjects with uneventful follow-up, patients with a primary outcome event had larger unipolar low-voltage zones (32.3 [6.1] cm2 vs. 20.7 [6.5] cm2, p=0.043) and bipolar dense scar areas (6.1 [2.3] cm2 vs. 1.8 [0.7] cm2, p=0.005), and after pooling mapping points from all patients, unipolar electrogram amplitude was moderately associated with primary outcome events (AUC: 0.65 [95% CI, 0.64-0.65]). Conclusions In CA, electrogram amplitudes are around the lower limit of normal, yet disproportionately low compared to the increased wall thickness. We found evidence that unipolar electrogram amplitude may be a quantitative marker of amyloid burden, possibly associated with adverse clinical outcomes.EVM and EMB in ATTR cardiac amyloidosisEVM and EMB in AL cardiac amyloidosis