Amyloid Cardiomyopathy Research Articles

Sodium-Glucose Cotransporter 2 Inhibitors in Patients With Amyloidosis With or Without Heart Failure.

Emerging evidence suggests sodium-glucose cotransporter 2 inhibitors (SGLT2i) benefits may extend to patients with amyloid cardiomyopathy, including transthyretin and amyloid light-chain amyloidosis subtypes. This study explores the broader implications of SGLT2i therapy across the spectrum of amyloidosis. This retrospective cohort study used de-identified electronic health records from the TriNetX platform, encompassing data from 101 healthcare organizations between 2009 and 2024. Two cohorts of amyloidosis patients with heart failure were compared based on SGLT2i use. One cohort without a diagnosis of heart failure was also tested. Propensity score matching was applied to balance baseline characteristics. The primary outcome was all-cause mortality, and secondary outcomes included acute heart failure, acute myocardial infarction, stroke, and chronic kidney disease. The matched cohorts included 5612 patients, with a mean age of 74 years and 64% male. SGLT2i-treated patients exhibited a higher 5-year survival probability (62.6%) compared to non-SGLT2i patients (39.1%) (HR: 0.54, 95% CI: 0.50-0.59; P < .001). In amyloidosis patients without heart failure (n = 1490), SGLT2i therapy was associated with a significant reduction in all-cause mortality (HR: 0.57, 95% CI: 0.43-0.74; P < .001). Sub-cohorts of transthyretin and amyloid light-chain amyloidosis in heart failure patients demonstrated consistent benefits with reduced mortality and favorable trends for acute myocardial infarction and stroke. SGLT2i therapy is associated with significant survival benefits in amyloidosis patients with HF and may offer broader advantages across the amyloidosis spectrum, including amyloid patients without heart failure.

SGLT2i effects depending on functional capacity in ATTR-CM

Abstract Introduction Heart failure (HF) with exercise intolerance is a common symptom of transthyretin amyloid cardiomyopathy (ATTR-CM), often initially presenting with preserved ejection fraction that deteriorates over time. In recent years, SGLT2 inhibitors (SGLT2i) have developed to a central component in the management of heart failure with both preserved and reduced ejection fraction. SGLT2i shows improvements in exercise capacity parameter, such as peak VO2, in HF patients. However, it remains unclear whether the benefits of SGLT2i are independent of disease condition and progression. Methods Patients with ATTR-CM underwent cardiopulmonary exercise testing (CPET) prior to initiating SGLT2i treatment and again 6 months (range: 4 to 8 months) later. We conducted a Pearson correlation to assess the relationship between baseline peak VO2 values and the change in peak VO2 from baseline to follow-up. Patients were then grouped based on prognostically significant peak VO2 cutoffs, specifically above and below 14 ml/kg/min. A Fisher's exact test was used to evaluate whether there were significant differences in improvement or deterioration between these two prognosis groups. Given the exploratory nature of this pilot study and the limited sample size, a significance threshold of p &amp;lt; 0.1 was chosen to accommodate the small cohort size and detect potential trends. Results A total of 34 patients with amyloid cardiomyopathy were included, with a mean age of 77 years (±6), 85% of whom were male. The median B-type natriuretic peptide level was 1115 pg/mL (range: 188-6300). Patients had an average peak VO2 of 16.2 (±5.1) ml/kg/min and a mean VE/VCO2 slope of 38.7 (±9). Comorbidities included coronary heart disease (35%) and diabetes mellitus (19%). At baseline, 82% (28 patients) of the patients were receiving Tafamidis, 17 patients (50%) were on angiotensin-converting enzyme inhibitors or angiotensin II receptor type 1 inhibitors, 11 (34%) were taking beta-adrenergic blockers, and 12 (35%) were being treated with mineralocorticoid receptor antagonists. The Pearson correlation showed a significant coefficient of -0.3 (p = 0.084) between baseline peak VO2 and the change in peak VO2 during study period. Additionally, a Fisher's exact test indicated a significant difference between the two groups (p = 0.08), with patients having a peak VO2 below 14 ml/kg/min showing a higher rate of improvement compared to those above this threshold. Conclusion There is an observable trend suggesting that SGLT2i may have more favourable effects in ATTR-CM patients with poor functional capacity. Further studies with larger cohorts are needed to validate this finding.Graphic Abstract

Detection of amyloid deposition in the hip and shoulder joints on CT scans as indicative of ATTR-type cardiac amyloidosis.

BackgroundAmyloid deposition manifests as thickening and calcification of the joints on computed tomography (CT) images.PurposeTo investigate the diagnostic potential of thickening and calcification of the shoulder and hip joints for the detection of transthyretin amyloid cardiomyopathy (ATTR-CM).Material and MethodsWe included 19 patients who had been assessed using 99mTc-pyrophosphate scintigraphy between January 2019 and December 2022 and diagnosed with ATTR-CM. The incidence of calcification and synovial thickening in the hip and shoulder joints of the patients and controls was evaluated. Two radiologists determined differences in joint calcification and thickness on CT images using Pearson chi-square tests and unpaired t-tests, respectively.ResultsShoulder and hip joint thickness (both P < 0.01) and calcifications (P < 0.05) significantly differed between the groups. The area under the receiver operating characteristic curve (AUC) was 0.74 for the shoulder joint, and the cut-off Youden index was 16.1 mm, with a sensitivity and specificity of 63.2% and 78.9%, respectively. The AUC was 0.844 for the hip joint, with an optimal cutoff of 11.8 mm, with a sensitivity and specificity of 71.4% and 89.5%, respectively. Inter-observer agreement was substantial between the radiologists for detecting hip and/or shoulder joint calcification (κ = 0.712). The interclass correlation coefficients (2, 1) were 0.65 and 0.71 for measurements of shoulder and hip joint thickness, respectively.ConclusionThickened and calcified shoulder and hip joints are more likely to be found in patients with clinically diagnosed ATTR-CM than those without.

Echocardiographic features of amyloid cardiomyopathy phenotypes in patients with different types of amyloidosis

Aim. To determine the echocardiographic variants of phenotype presentation of amyloid cardiomyopathy (ACM) in patients with different types of amyloidosis. Materials and methods. The study included 54 patients with ACM: 27 with light chain amyloidosis (15 [56%] males; the median age was 63.0 [56.5; 67.0]) and 27 patients with transthyretin amyloidosis (20 [74%] males; the median age was 73.0 [65.5; 78.5]). Standard echocardiographic parameters and the left ventricular (LV) global longitudinal strain in both groups were evaluated. Results. Among patients with ACM, the following phenotypes were reported: hypertrophic phenotype (HP), a combination of hypertrophic and restrictive phenotypes (HP+RP), a combination of hypertrophic, restrictive phenotypes and ejection fraction (EF) less than 50% (HP+RP+EF50%), and patients with minimal structural changes. In patients with HP+RP+EF50%, significantly greater thickness of the LV posterior wall (p=0.025) and the relative wall thickness (p=0.010) were found; the LV global longitudinal strain was lower (p=0.001). There were significant differences in the size of the right atrium (p=0.036), the systolic pressure in the pulmonary artery (p0.001), and the presence of a thickening of the free wall of the right ventricle (p0.007) in the HP+RP group. Involvement of the heart valves was more common in patients with ATTR ACM. Conclusion. After reviewing the echocardiographic data of patients, various phenotypic presentations of ACM and several correlations between echocardiographic characteristics depending on the type of amyloidosis were determined. Further study of echocardiographic parameters in patients with various types of amyloidosis may be promising for early diagnosis and proper treatment of ACM.

Current Landscape of Therapies for Transthyretin Amyloid Cardiomyopathy.

Current Landscape of Therapies for Transthyretin Amyloid Cardiomyopathy.

Impact of Sodium-Glucose Cotransporter-2 Inhibitors on Cardiovascular Outcomes in Transthyretin Amyloid Cardiomyopathy.

Impact of Sodium-Glucose Cotransporter-2 Inhibitors on Cardiovascular Outcomes in Transthyretin Amyloid Cardiomyopathy.

Imaging features of wild-type transthyretin amyloid cardiomyopathy in gated and non-gated contrast-enhanced CT.

Wild-type transthyretin amyloid cardiomyopathy (ATTR-CM) could be common, but its diagnosis is often overlooked. If the imaging features of ATTR-CM can be identified using conventional computed tomography (CT), which is commonly employed in clinical practice, its diagnostic value would be great. This study aimed to assess the imaging features of the condition in conventional non-gated contrast-enhanced CT. We retrospectively analyzed 43 consecutive patients diagnosed with wild-type ATTR-CM and performed a semi-quantitative evaluation of myocardial hypo-enhancement in the portal venous phase of conventional contrast-enhanced CT. A myocardial hypo-enhancement score (MHES) was calculated and compared between patients with ATTR-CM and 43 age-, sex-, height-, and weight-matched controls. Correlations between the score and clinical parameters such as the myocardial extracellular volume fraction (ECV) were also assessed. The MHES was significantly higher in the ATTR-CM group than in the control group (p < 0.01). It was also significantly higher in the high-ECV ATTR-CM subgroup (> 55%) than in the low-ECV ATTR-CM (≤ 55%) subgroup and the control group. There was good agreement between myocardial hypo-enhancement and late enhancement (kappa = 0.43), with 90.4% of the hypo-enhanced segments showing late enhancement. The detection sensitivity of late enhancement segments was higher in gated coronary CT angiography than in non-gated portal venous phase CT (69.2% vs 87.1%, p < 0.01). Wild-type ATTR-CM exhibited a tendency for myocardial hypo-enhancement, predominantly in the basal segments on conventional non-gated contrast-enhanced CT, suggesting an association with myocardial microcirculatory dysfunction. Question Can myocardial hypo-enhancement in non-gated contrast-enhanced CT help diagnose wild-type ATTR-CM, particularly in settings where late iodine enhancement imaging is unavailable? Findings Hypo-enhancement, predominantly in basal segments, was higher in ATTR-CM patients and correlated with ECV and global longitudinal strain, suggesting microcirculatory dysfunction. Clinical relevance Identifying myocardial hypo-enhancement in basal segments on conventional non-gated contrast-enhanced CT may provide a valuable diagnostic clue for ATTR-CM, particularly in facilities lacking LIE imaging, allowing for earlier recognition and potential clinical intervention.

Prevalence of transthyretin amyloid cardiomyopathy in an unselected cohort with heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) represents aheterogeneous syndrome characterised by various underlying aetiologies, such as transthyretin amyloid cardiomyopathy (ATTR-CM). The aim of this study was to determine the true prevalence of ATTR-CM in aDutch all-comers cohort of HFpEF patients. From 2018 to 2023, all patients diagnosed with HFpEF underwent prospective screening for ATTR-CM. Diagnosis of ATTR-CM was made in accordance with guideline recommendations. Of the 202 HFpEF patients included (mean ± standard deviation age: 76 ± 7years; 64% female), 9(5%) showed cardiac uptake on scintigraphy, of whom 6(3%) were subsequently diagnosed with wild-type ATTR-CM. Left ventricular wall thickness (LVWT) was significantly higher in ATTR-CM patients than non-amyloid HFpEF patients (median interventricular septum diameter: 15 mm; interquartile range (IQR): 11-17 vs 10 mm; IQR: 9-11; p < 0.001). Interestingly, 2ATTR-CM patients (33%) did not have increased LVWT at the time of diagnosis. These2patients were in aless advanced prognostic stage. This study revealed alow prevalence of ATTR-CM (3%) in an unselected HFpEF cohort. We identified ATTR-CM patients without increased LVWT (33%), who presented at an earlier disease stage. Hence, relying exclusively on LVWT for the diagnosis of ATTR-CM may result in delayed and/or missed diagnoses.

Delays in diagnosis and treatment of ATTR cardiac amyloidosis: A real-world data analysis.

Cardiac amyloidosis leads to functional cardiac impairment and heart failure. Transthyretin amyloid cardiomyopathy (ATTR-CM) is the most common form. After initial suspicion, diagnosis involves imaging techniques, biopsy and genetic tests, prompting transthyretin stabilizer therapy to slow disease progression. The study aims to assess delays in diagnosis in ATTR-CM patients. Patients with ATTR-CM receiving transthyretin stabilizer therapy at the West German Amyloidosis Center (01/2018-12/2023) were included. Clinical, laboratory, and imaging data were analysed. Diagnostic timelines were compared across two periods (2018-2020 and 2021-2023). After screening 254 patients, 154 were included in the analysis. ATTRwt was the most common form (96.8%). The median age was 80 (76-83) years, 87% were male and 46.6% were NYHA class ≥III. Time to diagnosis decreased from 398 to 277days in the second period (P<0.001). The median duration from diagnosis to stabilizer therapy was 84 (44-160) days, reducing from 111 (55-237) days in the first period to 57 (36-102) days in the second period (P<0.001). Patients diagnosed in the first period had lower LVEF (P<0.001) and more advanced NAC stages (P=0.004). More women were diagnosed in the second period (P=0.010). ATTR-CM is associated with diagnostic delays from initial suspicion to therapy initiation. While diagnostic and treatment timelines have improved, enhanced awareness, supraregional networks, specialized centres and focused education are essential to improve diagnosis and outcomes. Increasing awareness has led to patients being diagnosed at earlier disease stages, underscoring the potential to positively impact patient prognosis.

Cardiopulmonary Exercise Testing Correlates with Quantitative Left Ventricular [99mTc]-DPD Uptake in Transthyretin Amyloid Cardiomyopathy.

Background/Objectives: Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) often experience significantly reduced functional capacity due to myocardial involvement. Cardiopulmonary exercise testing (CPET) is the gold standard to quantify functional capacity, and 99mTc-DPD scintigraphy and SPECT/CT have proven to be highly effective tools for diagnostic and disease monitoring. We aimed to investigate the complementary role and correlation between both methods, focusing on their combined potential as a strong prognostic framework for monitoring disease progression and evaluating treatment efficacy. Methods: A total of 44 patients with diagnosed ATTR-CM, who underwent 99mTc-DPD scintigraphy and SPECT/CT imaging as well as CPET, were included. All patients were divided into two groups based on the median DPD retention index (low DPD uptake: ≤5.0, n = 22; high DPD uptake: >5.0, n = 22). Results: The mean age was 78 years, with 82% of participants being male. Significant correlations were observed between peak VO2 and DPD retention index (r = -0.355, p = 0.018) as well as between peak VO2 at anaerobic threshold with DPD retention index (r = -0.391, p = 0.009). Interestingly, there was no strong correlation between VE/VCO2 slope and the retention index. A strong association was identified between cardiac biomarkers and peak VO2, specifically for NT-proBNP (r = -0.530, p < 0.001) and Troponin T (r = -0.431, p < 0.001). Conclusions: In ATTR-CM, significant correlations were observed between key CPET parameters and quantitative cardiac DPD uptake, which further reflects on disease severity and functional impairment. Our findings highlight the utility of integrating CPET and SPECT/CT for comprehensive patient assessment in ATTR-CM.

A quantitative SPECT/CT metric for diagnosing transthyretin cardiac amyloidosis: multicenter study on biopsy-confirmed cases.

99mTechnetium-pyrophosphate ([99mTc]Tc-PYP) scintigraphy is the gold standard for diagnosing transthyretin amyloid cardiomyopathy (ATTR-CM). Conventional metrics, such as heart-to-contralateral-chest (H/CL) ratio and visual Perugini score, can be influenced by physiological blood pool uptake, leading to false positives and additional patient burdens. This study aimed to develop and validate a simple quantitative metric widely applicable for ATTR-CM diagnosis. This multicenter retrospective study enrolled 253 patients who underwent [99mTc]Tc-PYP SPECT/CT between April 2021 and September 2024. SPECT/CTs were acquired 3h post-injection of 740 MBq [99mTc]Tc-PYP. A lateral wall-to-aorta (LW/Ao) ratio was obtained by dividing the average radiotracer count in the lateral wall of the left ventricle by the average count in the ascending aorta. The diagnosis of ATTR-CM diagnosis was determined by endomyocardial biopsy. As statistical analyses, area under receiver operating characteristic (AUC) was used to compare diagnostic accuracy, and intraclass correlation coefficient (ICC) was used to assess inter-rater agreement. Among 52 patients (31 men; mean age 77) whose biopsy results were available, 11 were diagnosed with ATTR-CM. LW/Ao ratio showed a sensitivity of 100% (11/11), specificity of 97.6% (40/41), and positive likelihood ratio of 41.0. LW/Ao ratio showed higher AUC (0.99; 95% CI: 0.99-1.00) compared to H/CL ratio (AUC = 0.90, p = 0.04) and visual score (AUC = 0.87, p < 0.01). The ICC of LW/Ao ratio was excellent (0.91 ≥ 0.9). The quantitative SPECT/CT metric demonstrated superior diagnostic accuracy for ATTR-CM compared to conventional methods.

High rate of false negative 99mTc-pyrophosphate scintigraphy scans in patients with Leu58His transthyretin amyloid cardiomyopathy

High rate of false negative 99mTc-pyrophosphate scintigraphy scans in patients with Leu58His transthyretin amyloid cardiomyopathy

Efficacy of sinus rhythm maintenance after catheter ablation for atrial fibrillation in patients with transthyretin amyloid cardiomyopathy.

Efficacy of sinus rhythm maintenance after catheter ablation for atrial fibrillation in patients with transthyretin amyloid cardiomyopathy.

Use of technetium-99m-pyrophosphate single-photon emission computed tomography/computed tomography in monitoring therapeutic changes of RNA interference therapeutics in patients with hereditary transthyretin amyloid cardiomyopathy

Use of technetium-99m-pyrophosphate single-photon emission computed tomography/computed tomography in monitoring therapeutic changes of RNA interference therapeutics in patients with hereditary transthyretin amyloid cardiomyopathy

Unexpected and Successful ABO Incompatible Heart Transplant in a 50-year-Old Woman with AL Amyloid Cardiomyopathy

Unexpected and Successful ABO Incompatible Heart Transplant in a 50-year-Old Woman with AL Amyloid Cardiomyopathy

A Multicenter Study of Contemporary Long-Term Tafamidis Outcomes in Transthyretin Amyloid Cardiomyopathy.

A Multicenter Study of Contemporary Long-Term Tafamidis Outcomes in Transthyretin Amyloid Cardiomyopathy.

Early Amyloid Diagnosis and Treatment: Experience of Single Hand Surgeon With a Series of 182 Carpal Tunnel Biopsies.

Amyloidosis is a systemic disease characterized by buildup of abnormal amyloid deposits that may lead to multiple organ failure and is associated with early onset musculoskeletal manifestations. Orthopedic surgeons are positioned to aid with early diagnosis in the form of a biopsy which allows for workup for other areas of disease, specifically cardiac manifestations, and intervention prior to irreversible cardiac damage. In this review, we describe the biopsy results of a series of 182 patients and workup and treatment of the 46 amyloid positive patients biopsied by a single surgeon during a 4-year period. We retrospectively reviewed biopsy results from 2019 to 2024 for all patients who met criteria for biopsy at time of open carpal tunnel release (CTR). All surgeries were performed by a single surgeon at a single academic institution. Patient selection was based on a previously published algorithm. Forty-six (25.3%) of 182 patients who underwent CTR and met criteria for biopsy were found to test positive on Congo red staining and liquid chromatography tandem mass spectrometry. All 46 patients were referred to cardiology for evaluation. Thirty-three patients completed cardiology evaluation and 32 of those patients were started on treatment as a result of testing. The incidence of amyloid positive biopsy results was 25.3% in a single surgeon, single institution study using currently accepted screening criteria. All positive patients were referred for cardiac imaging and evaluation to obtain early diagnosis of amyloid cardiomyopathy and initiate treatment if indicated. A significant portion of patients referred to cardiology (58%) were started on pharmacological management as a result. Retrospective cohort study, II, prognostic.

Combination of familial transthyretin amyloidosis and hyperlipoproteinemia(a) in a patient with spinal canal stenosis: a case report

Hereditary transthyretin amyloidosis is a rare, progressive, systemic autosomal dominant disorder characterized by the extracellular deposition of insoluble amyloid fibrils in the peripheral nervous system, heart, and other organs. Among the specific signs of this condition, symptomatic spinal canal stenosis is prominent. Lipoprotein(a) is an atherogenic lipoprotein, and increased plasma concentrations are a significant risk factor for cardiovascular and cerebrovascular diseases. Data regarding the relationship between transthyretin amyloidosis and lipoprotein(a) levels are limited. This article presents a clinical case of a patient with arterial hypertension, with blood pressure elevated to 150/90 mmHg for 5 years. Following a COVID-19 infection between June 2, 2021, and June 25, 2021, the patient experienced a marked increase in blood pressure to 290/150 mmHg; sharp left-sided chest pain lasting 20–30 minutes unrelated to physical activity, which was relieved with medication; and pain in the cervical and thoracic spine. Despite antihypertensive therapy, the patient’s blood pressure stabilized at 110/70 mmHg. Further evaluation revealed dyslipidemia, with increased low-density lipoprotein cholesterol levels at 4.53 mmol/L and lipoprotein(a) at 1.46 g/L. Doppler ultrasound revealed atherosclerosis in the extracranial parts of the brachiocephalic arteries, with up to 20% stenosis of the right internal carotid artery. Echocardiography showed thickening of the left ventricular wall, interatrial septum, and mitral valve leaflets, although the ejection fraction remained preserved. Magnetic resonance imaging of the spine revealed cervical spinal canal stenosis (C5–C6). Genetic testing identified a nucleotide sequence variant in the transthyretin gene (Chr18: 29171879 GA, p. Arg5His) in the heterozygous state in the patient and her blood relatives. Specific anti-amyloid therapy with tafamidis was considered, and hypolipidemic therapy was initiated. In patients with symptomatic spinal canal stenosis and left ventricular wall thickening, even in the presence of hypertension, comprehensive evaluation is crucial for the timely diagnosis and adequate management of amyloid cardiomyopathy. Thus, we describe the first reported clinical case of the combination of familial transthyretin amyloidosis and hyperlipoproteinemia(a).

MRI-Extracellular Volume Fraction Versus Histological Amyloid Load in Cardiac Amyloidosis: The Importance of T2 Mapping.

Magnetic resonance imaging (MRI)-derived myocardial extracellular volume fraction (ECV) is elevated in the presence of fibrosis, amyloid deposition, inflammation, and edema. In patients with cardiac amyloidosis and prolonged T2 due to concomitant inflammation or edema, MRI-ECV may not correctly reflect histological amyloid load. The authors sought to determine whether MRI-ECV can accurately reflect histological amyloid load in 2 groups of patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM), with and without T2 prolongation. This retrospective study included consecutive patients with ATTRwt-CM who underwent endomyocardial biopsy and cardiac MRI from March 2017 to October 2021 for initial evaluation of ATTRwt-CM. We measured MRI-ECV and T2, and evaluated correlation between MRI-ECV and amyloid load from endomyocardial biopsy by means of Pearson correlation analysis. Of 44 patients (mean age, 75±6 years [SD]; 40 men), 24 showed T2 prolongation (T2≥50 milliseconds). All specimens obtained by endomyocardial biopsy were suitable for analysis. The interval between endomyocardial biopsy and cardiac MRI examination was a median of 3 days (interquartile range, 2-4). In the absence of T2 prolongation due to increased water content, MRI-ECV and amyloid load showed a moderately significant correlation (Spearman ρ=0.50, P=0.03). However, in the presence of T2 prolongation, there was no significant correlation between MRI-ECV and amyloid load (Spearman ρ=-0.05, P=0.83). In patients with ATTRwt-CM and prolonged T2, MRI-ECV did not accurately reflect histological amyloid load. Our findings underscore the need for a multiparametric imaging approach, combining both ECV and T2 mapping, to better characterize myocardial tissue in patients with ATTRwt-CM, and further prospective research in larger and more diverse cohorts is needed to validate our results.

Acoramidis (Attruby) for transthyretin amyloid cardiomyopathy.

The FDA has approved acoramidis (Attruby – BridgeBio), an oral transthyretin stabilizer, to reduce cardiovascular-related hospitalization and cardio-vascular death in adults with wild-type or variant (hereditary) transthyretin amyloid cardiomyopathy (ATTR-CM). Acoramidis is the second transthyretin stabilizer to be approved in the US for this indication; tafamidis (Vyndaqel, Vyndamax) was approved in 2019.