We sought to compare the long-term outcomes in patients with transthyretin cardiac amyloidosis (CA) compared to those with non-ischemic cardiomyopathy (NICM) from a large healthcare system database.

Patients with CA or NICM were identified from SSM Healthcare System's data warehouse using ICD codes. Inclusion criteria included at least 6 months of follow-up. Outcomes studied were heart failure hospitalization (HFH), ventricular tachyarrhythmias (VTA), implantable cardiac defibrillator (ICD) and pacemaker (PM) placement. Multivariate logistic analysis and Kaplan-Meier survival curves were constructed.

We identified 231 patients with CA and 462 with NICM, matched for age, race, and gender. CA patients had higher incidence of peripheral vascular disease (48.5% vs. 35.5%) and coronary artery disease (10.4% vs. 6.1%). Mean follow-up was 48.1 ± 33.1 months. CA patients had a higher rate of HFH (57.6% vs. 46.1%) and a lower rate of ICD (1.7% vs. 5.9%). In the multivariate model, CA patients had significantly higher odds for HFH (odds ratio: 1.86; 95% confidence interval: 1.29 - 2.68). Kaplan-Meier survival curves showed a trend toward earlier HFH and later PM or ICD implantation in CA patients.

In this retrospective study from a large healthcare system database, compared to NICM, transthyretin CA patients had significantly higher rates of HFH, similar odds of VTA, and a lower likelihood of receiving an intracardiac device.

Cardiac amyloidosis (CA) is a prevalent yet underdiagnosed heart condition characterized by the abnormal accumulation of amyloid fibres, frequently resulting in heart failure (HF), particularly in older people. Despite advancements in non-invasive diagnostic techniques and treatments, the epidemiology of CA patients remains inadequately understood. This nationwide retrospective observational study sought to comprehensively investigate CA patients' characteristics, mortality, and readmission patterns.

A retrospective observational study encompassed all patients hospitalized with CA between 2016 and 2021 across Spanish hospitals. Standardized incidence rates were calculated using age and sex-adjusted methods, utilizing the Spanish population as the reference. The investigation delved into demographic variables, comorbidities, mortality during the index episode, and 30 and 365-day readmissions for circulatory system diseases. Predictors of readmission were also examined.

A total of 5739 index episodes were identified, with CA being the primary cause of admission in 14.1% of cases. The mean age was 81.4 ± 9.9 years, predominantly males (70.3%). The age and sex-standardized hospital attendance rate was 3.90 admissions per 100,000 population (95% CI: 3.82-3.98), higher in males. Common comorbidities included HF (96.4%), atrial fibrillation (46.3%), and renal failure (44.4%). The mortality rate during the index episode was 11.7%, with cardiogenic shock (OR: 9.03; 95% CI: 4.22-19.32) and major psychiatric disorders (OR: 3.36; 95% CI: 1.42-7.94) identified as predictors. Over the follow-up period, 13.1% were readmitted at 30 days and 36.6% at 365. Nephritis (IRR: 2.05; 95% CI: 1.42-2.96) and asthma (IRR: 1.52; 95% CI 1.11-2.07) were associated with increased 30-day readmissions, while renal failure (IRR: 1.43; 95% CI: 1.28-1.59) and chronic pulmonary disease (IRR: 1.40; 95% CI: 1.18-1.67) were linked to higher 365-day readmissions. Predictors of mortality risk in 365-day readmissions included advanced cancer (HR: 1.31; 95% CI: 1.00-1.71), cardiogenic shock in the index episode (HR: 2.72; 95% CI: 1.33-5.57), and a higher number of readmissions during that period (HR: 1.64; 95% CI: 1.56-1.73).

This study contributes valuable insights into the significant prevalence of CA, which is often overlooked and underestimated. Afflicting predominantly elderly males with concomitant HF and multiple comorbidities, CA poses a significant clinical challenge. The findings underscore the need for enhanced awareness, early detection, and a multidisciplinary approach to manage this complex cardiac condition.

Cardiac amyloidosis is an infiltrative cardiomyopathy characterized by the abnormal accumulation of amyloid proteins within the heart muscle. It is recognized as a rare yet significant cardiac disease that is often overlooked as a potential cause of heart failure and cardiac arrhythmias, particularly in older individuals with rates escalating from 8 to 17 cases per 100,000 individuals. Cardiac amyloidosis primarily manifests as two predominant subtypes: light-chain and transthyretin amyloidosis, collectively accounting for over 95% of clinical cases. Early diagnosis of these conditions is often hindered by overlapping symptoms with other cardiac pathologies, resulting in diagnostic delays and suboptimal patient outcomes. Echocardiography, a non-invasive imaging technique, has become indispensable for diagnosing cardiac amyloidosis, uncovering crucial echocardiographic signs such as thickening of the left ventricular wall, diastolic dysfunction, and a granular appearance of the myocardium. Recent advancements in echocardiography have significantly enhanced the diagnostic accuracy of cardiac amyloidosis and improved patient management. Advanced echocardiographic techniques, including strain imaging, 3D echocardiography, and contrast echocardiography, have significantly enhanced diagnostic accuracy and prognostication. Future directions in echocardiography encompass the integration of artificial intelligence, the development of novel contrast agents, and the refinement of 4D echocardiography to further optimize patient care. This study explores the pivotal role of echocardiography in both diagnosing and managing cardiac amyloidosis, delving into the disease's underlying mechanisms, distinctive imaging characteristics, the significance of regular echocardiographic assessments, and discusses the challenges associated with differentiating between various types of amyloidosis without supplemental imaging or biopsy methods.

Background: ATTRv and ATTRwt cardiac amyloidosis (CA) are underrecognized causes of heart failure with preserved left ventricular ejection fraction. The diagnosis of CA remains challenging due to low diagnostic suspicion and clinical overlap with more common diseases. The aim of this study was to use [99mTc]-PYP SPECT-CT to perform a volumetric evaluation of bone scintigraphy to overcome the limitations of current practices. Methods: A monocentric prospective study was conducted to evaluate a lot of 22 patients with a mean age of 52.86 ± 13.80 years, diagnosed with hereditary cardiac transthyretin amyloidosis (ATTR). Results: Correlations between the quantitative SPECT-CT, clinical data, and morphological parameters were performed, demonstrating moderate to strong correlation of SUVmaxMyocardium/SUVmaxBone to both ECG low voltage and EchoGLS, SUVmaxMyocardium/SUVmaxLiver to myocardial gadolinium kinetics with T1 mapping MRI, diastolic disfunction, sensory-motor polyneuropathy, and EchoGLS, SUVmaxMyocardium/SUVmeanBone with diastolic disfunction and sensory-motor polyneuropathy, as well as SUVmaxMyocardium/SUVmaxSoft tissue to S II, respectively. Conclusions: The moderate to strong correlations among advanced quantitative SPECT-CT metrics and clinical and paraclinical data create the premises to use these parameters for early diagnosis of cardiac ATTR. Further multicentric studies in a larger patient population are needed to validate the newly identified quantitative SPECT-CT parameters.

Despite the high accuracy of AI-based automated analysis of 12-lead ECG images for classification of cardiac conditions, clinical integration of such tools is hindered by limited interpretability of model recommendations. We aim to demonstrate the feasibility of a generic, clinical resource interpretability tool for AI models analyzing digitized 12-lead ECG images. To this end, we utilized the sensitivity of the Jacobian matrix to compute the gradient of the classifier for each pixel and provide medical relevance interpretability. Our methodology was validated using a dataset consisting of 79,226 labeled scanned ECG images, 11,316 unlabeled and 1807 labeled images obtained via mobile camera in clinical settings. The tool provided interpretability for both morphological and arrhythmogenic conditions, highlighting features in terms understandable to physician. It also emphasized significant signal features indicating the absence of certain cardiac conditions. High correlation was achieved between our method of interpretability and gold standard interpretations of 3 electrophysiologists.

Postoperative cognitive dysfunction (POCD) is defined as a declined cognition, measured by neuropsychological tests, that persists for months or even longer after surgery. Heterogeneities in the diagnosis of POCD usually involve differences in the test batteries, the cutoffs, and the timing of assessments. Although peripheral and CSF markers of neuroinflammation have been shown to correlate with increased risk of POCD, most of them are non-specific and cannot be used for POCD diagnosis. These factors hampered the understanding of the pathogenesis of POCD as well as the development of effective preventions/treatments. In this study, we found Ttr in a panel of potential POCD biomarkers identified using time-series analysis of the transcriptomes and proteomes of the hippocampi of POCD mice that diagnosed on individual basis with composite Z-scores of test batteries consisting of Y maze and open field test. Compared with their counterparts without POCD, the levels of Ttr were significantly lower in the peripheral circulation as well as in the hippocampi of the mice developed POCD at all indicated time points after surgery. The levels of peripheral TTR in human patients with delayed neurocognitive recovery were found to be reduced at 24 h after abdominal surgery, compared with those who did not. Endogenous expression of Ttr was verified in microglia cells both in vitro and in vivo. Results of in vitro assay indicated a potential role of Ttr in ameliorating LPS-induced microglial priming and protecting the differentiation of oligodendrocyte progenitor cells (OPCs) in proinflammatory microenvironment, which was one of the determinant factors in regulating the pathological progression of POCD.

To evaluate the feasibility of identifying various distribution patterns of [99mTc]Tc-DPD in patients with cardiac transthyretin amyloidosis using gated SPECT-CT.

Gated SPECT-CT was performed in patients with a positive scintigraphy result for cardiac amyloidosis due to transthyretin (TTR-CA). Patients were categorized into several groups based on sex, degree of radiopharmaceutical uptake according to the Perugini's visual scale and ventricular ejection fraction (LVEF). Cardiac polar maps were obtained using Emory Cardiac Toolbox™ software and scored by segments according to radiopharmaceutical uptake on a scale from 0 (no uptake) to 4 (very high uptake intensity). The Mann-Whitney U and Pearson's Chi-square statistical tests were employed to identify significant differences in distribution patterns according to the different variables under study.

65 patients were evaluated. The gender variable determined the main statistically significant differences, highlighting distinct distribution patterns of the radiopharmaceutical at the cardiac level: while women showed lower accumulation of [99mTc]Tc-DPD in the middle anterior (p=0.035) and basal anterior (p=0.001) segments, whereas men demonstrated higher accumulation in the basal anteroseptal (p=0.009) and basal inferoseptal (p=0.009) segments, and lower scores in the lateroapical segment (p=0.039).

Gated SPECT-CT is an essential tool for assessing the distribution pattern of [99mTc]Tc-DPD of patients with TTR-CA, offering valuable insights into the pathophysiology of the disease.

Speckles tracking echocardiography imaging enables clinicians to detect subtle systolic dysfunction. The aim of the present study was to elucidate the differences in speckle tracking echocardiographic findings between immunoglobulin light chain amyloid cardiomyopathy (AL-CM) and transthyretin amyloid cardiomyopathy (TTR-CM).

The patients with a confirmed diagnosis of cardiac amyloidosis through cardiac biopsy from March 2013 to October 2022 were included. The relative apical sparing index (RASI) was calculated using speckle tracking echocardiography by the following equation; average apical strain/(average basal strain + mid strain).

The final study population consisted of 35 patients with cardiac amyloidosis (AL-CM: 10 patients, TTR-CM: 25 patients). The mean age was 74 ± 12 years. Although both subgroups had a gradual change of strain values from basal to apical segments, RASI was significantly lower in AL-CM compared to TTR-CM (0.92 ± 0.29 vs. 1.46 ± 0.53, p = 0.001). A RASI cutoff value of <1.0 proved useful in differentiating the diagnosis of AL-CM from TTR-CM (sensitivity: 81%, specificity: 70%, AUC: 0.82). A significant positive correlation with left ventricular mass index and RASI was found in AL-CM, but not in TTR-CM.

The apical sparing phenomenon was more remarkable in TTR-CM compared with AL-CM. RASI might be useful for the discrimination of cardiac amyloidosis subtypes. There was a difference in the relationship of RASI with left ventricular wall thickness between the cardiac amyloidosis subtypes.

Amyloidosis is a group of diseases characterized by the deposition of misfolded protein fragments, forming insoluble fibrils in organs and tissues. Transthyretin (ATTR) amyloidosis, particularly cardiac amyloidosis (CA), leads to myocardial stiffness and heart failure. Right ventricular (RV) involvement is common in CA, but assessing RV stiffness noninvasively is challenging. This study aimed to evaluate RV stiffness using shear wave elastography (SWE) and correlate the findings with clinical, laboratory, and echocardiographic parameters.

In this prospective, single-center, cross-sectional study, 60 patients were divided into three groups: 20 with cardiac ATTR amyloidosis (ATTR-CM), 20 with non-cardiac ATTR amyloidosis (ATTR non-CM), and 20 healthy controls. Myocardial stiffness was measured using SWE in the free wall of the RV. Pearson's and Spearman's correlation coefficients were used for statistical analysis, with significance set at p < 0.05.

RV SWE values showed a strong positive correlation with functional class and a moderate correlation with BNP and troponin I levels. A significant negative correlation was found between RV SWE values and the 6-minute walk test distance. SWE also correlated with echocardiographic variables like interventricular septum thickness and RV basal diameter. An SWE cutoff of ≥ 4.6. kPa was associated with cardiac involvement, showing 65 % sensitivity and 76 % specificity.

SWE is a valuable noninvasive technique for assessing RV stiffness in CA patients, correlating well with clinical and echocardiographic parameters. An RV SWE value of ≥ 4.6 kPa could aid in early detection of cardiac involvement in ATTR amyloidosis, improving diagnosis and management.

Cardiac amyloidosis (CA) is a form of infiltrative, restrictive cardiomyopathy that presents a diagnostic and therapeutic challenge in clinical practice. Historically, it has led to poor prognosis due to limited treatment options. However, advancements in disease awareness, diagnostic tools, and management approaches have led to the beginning of an era characterized by earlier diagnosis and a broader range of treatments. This article examines the advances in treating the two primary forms of cardiac amyloidosis: transthyretin cardiac amyloidosis (ATTR-CA) and light chain mediated cardiac amyloidosis (AL-CA). It highlights therapies for ATTR-CA that focus on interrupting the process of amyloid fibril formation. These therapies include transthyretin stabilizers, gene silencers, and monoclonal antibodies, which have shown the potential to improve patient outcomes and survival rates significantly. As of this writing, tafamidis is the sole Food and Drug Administration (FDA)--approved drug for ATTR-CA; however, experts anticipate several other drugs will gain approval within 1-2 years. Treatment strategies for AL-CA typically involve chemotherapy to inhibit the clonal cell type responsible for excessive AL amyloid fibril production. The prognosis for both types of amyloidosis primarily depends on how much the heart is affected, with most deaths occurring due to progressive heart failure. Effective care for CA patients requires collaboration among specialists from multiple disciplines, such as heart failure cardiology, electrophysiology, hematology/oncology, nephrology, neurology, pharmacology, and palliative care.

Identification of transthyretin cardiac amyloidosis (ATTR-CA) patients is largely based on pattern recognition by providers, and this can be automated through electronic medical systems (EMR).

All patients in a large academic hospital with age > 60, ICD-10 code for chronic diastolic heart failure and no previous diagnosis of any amyloidosis were included. An Epic EMR scoring logic assigned risk scores to patients for ICD-10 and CPT codes associated with ATTR-CA, as follows: carpal tunnel syndrome (score 5), aortic stenosis/TAVR (5), neuropathy (4), bundle branch block (4), etc. The individual patients' scores were added, and patients were arranged in descending order of total scores- ranging from 50 to 0. Data is reported as median (interquartile range) and analyzed with non-parametric tests.

Of the total 11,648 patients identified, 132 consecutive patients with highest risk scores (score ≥ 30) were enrolled as cases, while 132 patients with scores between 10 and 19 with available echocardiography data served as age-matched controls. Strain echocardiography is not routinely performed. Patients with high scores were more likely to have CA associated findings- African-American race, higher left ventricular (LV) mass index and left atrial volume and lower LV ejection fraction. High score patients had higher troponin and a trend towards high NT-proBNP.

The modern EMR can be used to flag patients with high risk for ATTR-CA (score ≥ 30 using the proposed logic) through best practice advisory. This could encourage screening during echocardiography using strain or during unsuspected clinic visits.

Amyloidosis is a rare pathology characterized by protein deposits in various organs and tissues. Cardiac amyloidosis (CA) can be caused by various protein deposits, but transthyretin amyloidosis (ATTR) and immunoglobulin light chain (AL) are the most frequent pathologies. Protein misfolding can be induced by several factors such as oxidative stress, genetic mutations, aging, chronic inflammation, and neoplastic disorders. In ATTR cardiomyopathy (ATTR-CM), the amyloid fibrils can be found in the myocardium interstitial space and are associated with arrhythmias and heart failure. In pathological situations, the transthyretin (TTR) configuration is destroyed by proteolytic action, leading to monomers that further misfold and aggregate to form the amyloid fibrils. 99mTc-Pyrophosphate (99m-Tc-PYP), 99mTc 3,3-diphosphono-1,2-propanodicarboxylic acid (99m-Tc-DPD) and 99m-Tc hydroxy-methylene-Dyphosphonate (99m-Tc-HMDP) are used to detect myocardium amyloid deposits due to their ability to detect calcium ions that are present in the amyloid fibrils through dystrophic calcification. ATTR-CM therapy acts on different stages of the amyloidogenic process, including liver TTR synthesis, TTR tetramer destabilization, and misfolding of the monomers. The main aim of this narrative review is to present ATTR-CM, starting with molecular changes regarding the protein misfolding process and radionuclide aspects and finishing with pharmacological approaches.

Cardiac involvement in light chain amyloidosis (AL) is the main determinant of prognosis. Amyloid can be deposited in the extracellular space and cause an increase in extracellular volume fraction (ECV). At the same time, amyloid can also be deposited in the wall of small vessels and cause microvascular dysfunction. This study sought to investigate the extent of microvascular dysfunction and its incremental prognostic value in cardiac light-chain amyloidosis (AL-CA) by quantitative stress perfusion.

A total of 126 AL amyloidosis patients (61.13 ± 8.46 years, 81 male) confirmed by pathology were prospectively recruited. All subjects underwent cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE), T1 mapping, and stress perfusion on a 3T scanner. ECV and myocardial perfusion reserve (MPR) were measured semi-automatically using a dedicated CMR software. Clinical, laboratory, and CMR parameters were analyzed for their prognostic value in the assessment of AL-CA patients. Mortality-associated markers were analyzed by univariate and multivariable Cox regression.

The median follow-up time was 37 (33.6-40.4) months, and 62 patients died. The ECV of survivors was significantly reduced, but the stress myocardial blood flow and MPR were higher (P < 0.001). The MPR of the transmural LGE group was significantly lower than that of the no LGE and subendocardial LGE groups (P < 0.001). In multivariable analysis, ECV, MPR, and LGE were independently predictive. MPR of >1.5 and ECV of ≤53.6% were associated with improved overall survival, both of which provided predictive incremental value in patients with advanced disease. With equal Mayo staging and degree of ECV, MPR improves assessment of patient survival.

ECV and MPR showed additive incremental values and further discriminated prognosis of patients in advanced stages. CMR phenotypes with higher ECV and lower MPR had a worse prognosis.

BACKGROUND Amyloidosis is a group of diseases characterized by the pathological deposition of misfolded proteins in various organs, including the heart, leading to structural and functional alterations. The primary types of cardiac amyloidosis are light chain amyloidosis and transthyretin amyloidosis. Early diagnosis is critical for effective management. This report describes the case of a 68-year-old Colombian man presenting with heart failure and a diagnosis of cardiac amyloidosis. CASE REPORT A 68-year-old man presented with heart failure symptoms, biceps tendon rupture, neuropathic pain in the extremities, and an electrocardiogram showing low QRS voltage and a pseudo-infarct pattern. Transthoracic echocardiogram revealed a left ventricular ejection fraction of 30%, severely thickened walls with a speckled appearance, a global longitudinal strain of -6.2% in a bull's eye pattern, and a left ventricular posterior wall thickness of 21.3 mm. Cardiac magnetic resonance imaging showed severe symmetric hypertrophy, moderate global dysfunction, and an elevated native T1 value of 1225 milliseconds. Post-gadolinium T1 mapping revealed a significantly increased extracellular volume of 72%. Perugini grade 3 pyrophosphate scintigraphy, negative hematological tests, and endomyocardial biopsy confirmed the diagnosis of amyloidosis, without monoclonal spikes. Genetic testing identified a heterozygous c.424G>A (p.Val142Ile) variant in the transthyretin gene, consistent with variant transthyretin amyloidosis. CONCLUSIONS Amyloidosis may affect up to 13% of patients with heart failure and preserved ejection fraction. Early recognition of red flags and implementation of a diagnostic algorithm are crucial for timely intervention in this population.

Diagnosis of hereditary amyloid transthyretin (hATTR) amyloidosis with cardiomyopathy is frequently delayed, in large part because of symptom overlap with other cardiovascular diseases and limited provider knowledge of this disease. The sponsored and provider referred hATTR Compass Genetic Testing Program (Ionis, Carlsbad, CA; Ambry Genetics, Aliso Viejo, CA) provided no-cost genetic testing to adults with a family history or clinical suspicion of hATTR amyloidosis. This study aims to characterize patients with hATTR amyloidosis and increase awareness of genetic testing for hATTR.

Patients were referred to the hATTR genetic testing program, and a cross-sectional post hoc analysis was performed. A pathogenic TTR variant was identified in 1503 (6.6%) of 22 886 patients referred for genetic testing between June 2018 and March 2022. Patients were identified in all US states, 3 US territories, and Canada. Median age at testing was 63 years, and 44% were female. The p.V142I TTR variant was the most common (n=1263, 84.0%). Only 32% of patients with a pathogenic TTR variant reported a known family history; a lower percentage of Black individuals reported a known family history compared with other racial and ethnic groups. Black patients accounted for 23.7% of all patients referred and 81.9% of patients with the p.V142I variant.

This sponsored genetic testing program identified a large number of patients with a pathogenic TTR variant, notably, in geographic regions not previously reported, and demographic groups that are historically underrepresented in the literature.

Recognition of transthyretin amyloid cardiomyopathy is increasing due to advances in cardiac imaging and diagnostic strategies, but questions remain regarding disease frequency and characteristics. We examined the prevalence and characteristics of transthyretin amyloid cardiomyopathy in older patients with hypertrophic cardiomyopathy of unascertained aetiology.

TTRACK was a multicentre, non-interventional, cross-sectional epidemiologic study funded by Pfizer and conducted in 20 hospitals and medical centres in 11 countries (NCT03842163). Eligible patients were aged ≥50 years, had hypertrophic cardiomyopathy (maximal end-diastolic left ventricular wall thickness ≥15 mm on echocardiogram) without an identified genetic or alternative origin at study enrolment, and underwent 99mTechnetium bone scintigraphy, with or without single photon emission computed tomography (SPECT). Cardiac-versus-bone uptake on scans was visually scored from 0 to 3 (Perugini scoring). Patients with grades 1-3 underwent monoclonal protein and laboratory testing and transthyretin (TTR) gene sequencing. Of 766 eligible patients, 691 (90.2%) had scintigraphy alone and 75 (9.8%) scintigraphy plus SPECT. Two hundred and eight patients (27.2%) had grade 2 or 3 cardiac uptake on scintigraphy; 144 (18.8%) had grade 2 or 3 cardiac uptake and no evidence of plasma cell dyscrasia and were diagnosed with transthyretin amyloid cardiomyopathy. Of patients with transthyretin amyloid cardiomyopathy, 11 (7.6%) had a pathogenic TTR gene variant and 34 (23.8%), 74 (51.7%), and 35 (24.5%) had New York Heart Association class I, II, and III/IV heart failure (HF) symptoms, respectively. Clinical and laboratory diagnostic characteristics were observed in ≥90% of patients with transthyretin amyloid cardiomyopathy. The characteristics most strongly associated with transthyretin amyloid cardiomyopathy on multivariable analysis were carpal tunnel syndrome (odds ratio [OR] 54.3; P < 0.0001) and male sex (OR 7.9; P < 0.0001).

In the TTRACK study, almost one in five patients ≥50 years of age with hypertrophic cardiomyopathy had transthyretin amyloid cardiomyopathy. Greater awareness of the frequency and characteristics of transthyretin amyloid cardiomyopathy in older patients with hypertrophic cardiomyopathy are needed to help improve early detection of this debilitating but treatable disease.

The efficacy of beta-blockers in cardiac amyloidosis (CA) is unclear, and concerns persist that neurohormonal blockade could worsen symptoms of heart failure. We aimed to assess whether beta-blocker therapy is associated with improved survival in patients with CA.

We conducted a systematic review and meta-analysis to examine the impact of beta-blocker therapy on mortality in patients with CA. A search of MEDLINE and EMBASE was performed in August 2023. Data were extracted from observational studies and synthesized with pooling and random effects meta-analysis. Thirteen studies including 4215 patients with CA were incorporated in this review (3688 transthyretin amyloid cardiomyopathy (ATTR-CM), 502 light chain amyloid cardiomyopathy (AL-CM), 25 not specified; age 74.8 ± 5.5 years, 76% male). Over half of the cohort (52%) received beta-blockers and the rate of beta-blocker withdrawal was 28%. All-cause mortality was 33% (range: 13-51%) after a median follow-up ranging from 13 to 36 months. There was an inverse association between the pooled risk of mortality and the use of beta-blocker therapy at any time point (RR 0.48, 95% CI 0.29-0.80, I2 = 83%, P = 0.005, seven studies). There was no association between mortality and beta-blocker use (RR 0.65, 95% CI 0.29-1.47, I2 = 88%, P = 0.30) in the three studies that only included patients with ATTR-CM. The three studies that included patients with both ATTR-CM and AL demonstrated an association of beta-blocker use with reduced mortality (OR 0.43, 95% CI 0.29-0.63, I2 = 4%, P < 0.001). The only study that solely included 53 patients with AL-CM, demonstrated improved survival among the 53% who were able to tolerate beta-blocker therapy (RR 0.26, 95% CI 0.08-0.79, P = 0.02). The absence of information on staging of CA is an important limitation of this study.

Treatment with beta-blockers may be associated with a survival benefit in patients with CA, but these findings are subject to selection and survivor biases. Definitive prospective randomized trials of conventional heart failure therapies are needed in CA.

Carpal tunnel syndrome (CTS) and cardiac amyloidosis (CA) are seemingly disparate medical conditions but may be linked. CTS can be a sign of early CA, and CA can be a hidden cause of heart failure. Therefore, in this systematic review and meta-analysis, we aim to investigate the expected correlation between the occurrence of CTS and CA. A comprehensive search was conducted across multiple databases, including PubMed, Web of Science, Scopus, and Cochrane Library, to get relevant studies previously published before June 2023. No language restrictions were applied. Randomized clinical trials and observational studies have been included to investigate the proportion of patients reporting CA among patients with an established diagnosis of CA, and also the incidence of patients who have CTS among patients with CA has been investigated with a pooled estimation of the expected time from the diagnosis of CTS till the development of CA. Studies that did not report data on CTS or CA or lacked sufficient details were excluded. Meta-analysis of data for each outcome was performed using R version R.4.3.2 software (R Foundation for Statistical Computing, Vienna, Austria) using the Meta package. Heterogeneity across studies was assessed using the I² statistic. A meta-analysis of 15 studies, including 1416 patients, evaluated the relationship between CTS and CA. Among these, 495 patients with CTS were assessed for the presence of CA, and 915 patients with CA were evaluated for the presence of CTS. The pooled meta-analysis of eight studies, which included 915 patients with CA, revealed that 38% (95% CI: 35%-41%) had a history of CTS. Conversely, the proportion of patients with CTS who developed CA was 13% (95% CI: 4%-35%). The pooled mean time from CTS to the development of CA, based on 639 patients across four studies, was 6.02 years (95% CI: 3.76-8.36). Significant heterogeneity was noted for some outcomes (e.g., proportion of CA in patients with CTS: I²=93%), likely influenced by variations in study populations, age distributions, and diagnostic criteria. Our review of the literature suggests that there may be a link between CTS and CA. However, more research is needed to confirm this link and to understand how the two conditions are related. It is important to consider the possibility of CA in patients with CTS, as screening, early detection, and timely treatment can improve outcomes by slowing disease progression and reducing complications.

Cardiac amyloidosis is a rare but increasingly recognized cause of heart failure, often underdiagnosed until later stages of the disease. This report describes a case of transthyretin amyloidosis (ATTR) in a 68-year-old male patient with a significant medical history of rheumatoid arthritis (RA), a combination seldom documented in the literature. The patient presented with progressive symptoms of heart failure, and diagnostic testing confirmed ATTR cardiac amyloidosis through pyrophosphate (PYP) scanning. This case highlights the clinical presentation, diagnostic process, and management of cardiac amyloidosis while exploring a potential link between RA and amyloid deposition. Early recognition of cardiac amyloidosis is crucial for improving outcomes, especially in patients with coexisting systemic inflammatory conditions like RA.

Cardiac amyloidosis (CA) is a serious condition that results in infiltrative cardiomyopathy and heart failure with preserved ejection fraction (HFpEF) that is caused by the extracellular deposition of amyloid fibrils within heart tissue. While many important features of CA have been known for years, its prevalence in elderly patients with HF is increasingly being recognized. Plasma cells produce monoclonal immunoglobulin light chains which results in the formation and aggregation of amyloid fibrils that are responsible for AL amyloidosis. CA is classified as originating from either transthyretin (ATTR) or light chain (AL) amyloidosis. ATTR CA may result from a genetic mutation in the TTR gene, which is inherited (ATTRv), or from age-related deposition from wild-type ATTR (ATTRwt). Cardiac involvement in AL amyloidosis is attributed to either of two mechanisms: the extracellular deposition of amyloid fibril in the myocardium, or direct cardiotoxicity from the fibril aggregates. Typing of amyloid fibrils, a critical determinant of therapy, has also improved with wider availability of laser capture and mass spectrometry of histologic specimens. Specific and accurate evaluation of CA is now possible using cardiac magnetic resonance imaging and bone scintigraphy tracers. Survival in CA has improved markedly as novel chemotherapy agents have become available, but challenges remain in advanced disease. Broadening the amyloid-specific therapeutic landscape to include RNA inhibitors, fibril formation stabilizers and inhibitors, and immunotherapeutic targeting of amyloid deposits holds promise and may improve outcomes in systemic and cardiac amyloidoses. Treatment strategies for CA has recently undergone transformative changes, leading to some progress in outcomes for certain patients. Here, we discuss the basic features of CA as well as the emergence of novel, disease-modifying strategies that have been recently evaluated in clinical trials for the treatment of CA.

Cardiac amyloidosis is a rarely reported and potentially fatal variant of the systemic disease. Its early diagnosis could potentially lead to significantly improved clinical outcomes.

A 56-year-old female presented with dyspnea and palpitations. Her physical exam and non-invasive evaluation with cardiac magnetic resonance imaging (CMRI) revealed restrictive cardiomyopathy, and the bone marrow biopsy results showed systemic amyloidosis.

The diagnosis of cardiac amyloidosis is not always straightforward, and delay can cause the progression of the disease and an increased risk of morbidity and mortality. Electrocardiograms, echocardiograms, cardiac magnetic resonance imaging, and histopathologic evaluation are the main methods for diagnosing cardiac amyloidosis. The treatment consists of controlling heart failure symptoms and disease-modifying interventions, including medical and surgical therapeutic methods.

Cardiac involvement is the main cause of death in systemic amyloidosis. Early suspicion, diagnosis, and treatment are crucial in improving patients' survival. CMRI can play an essential role in the diagnosis of cardiac Amyloidosis. A graphical abstract is provided for visual summary.

Cardiac involvement is the most important factor determining prognosis in patients with systemic amyloidosis. This retrospective observational study of 98 patients with amyloidosis was undertaken to assess the amyloid types that are most likely to affect the heart, describe histopathological and clinical features of cardiac amyloidosis, and estimate the number of cases not diagnosed clinically prior to death. All cases were divided into two groups based on the method of examination. The first group included 46 patients with cardiac amyloidosis revealed via endomyocardial biopsies (EMBs), and the second group included 52 amyloidosis patients who did not undergo EMBs, in whom cardiac involvement was identified only at autopsy. The EMBs demonstrated that AL amyloidosis was detected in 21 (46%) specimens, ATTR amyloid in 24 cases (52%), and AA amyloid in 1 case (2%). The autopsy reports defined 15 (46%) cases of AL amyloidosis, 21 (40%) of ATTR and 16 (31%) of AA amyloidosis. It should be noted that a clinical diagnosis of ATTR amyloidosis was made only in 9.5% of patients from the autopsy group, suggesting that ATTR may be an underdiagnosed cause of heart failure in elderly patients. The most intense amyloid deposits were determined in biopsy and autopsy specimens of patients with AL kappa amyloidosis, underlying a poorer prognosis.

Systemic amyloidosis represents a heterogeneous group of diseases resulting from amyloid fibre deposition. The purpose of this study is to establish a differential diagnosis algorithm targeted towards the two most frequent subtypes of CA.

We prospectively included all consecutive patients with ATTR and AL evaluated between 2018 and 2022 in two centres in a score derivation cohort and a different validation sample. All patients had a complete clinical, biomarker, electrocardiographic, and imaging evaluation. Confirmation of the final diagnosis with amyloid typing was performed according to the current international recommendations. The study population included 81 patients divided into two groups: ATTR (group 1, n = 32: 28 variant and 4 wild type) and AL (group 2, n = 49). ATTR patients were younger (50.7 ± 13.9 vs. 60.2 ± 7.3 years, P = 0.0001), and significantly different in terms of NT-proBNP [ATTR: 1472.5 ng/L (97-4218.5) vs. AL 8024 ng/L (3058-14 069) P = 0.001], hs-cTn I [ATTR: 10 ng/L (4-20) vs. AL 78 ng/L (32-240), P = 0.0002], GFR [ATTR 95.4 mL/min (73.8-105.3) vs. AL: 68.4 mL/min (47.8-87.4) P = 0.003]. At similar left ventricular (LV) wall thickness and ejection fraction, the ATTR group had less frequently pericardial effusion (ATTR: 15% vs. AL: 33% P = 0.0027), better LV global longitudinal strain (ATTR: -13.1% ± 3.5 vs. AL: -9.1% ± 4.3 P = 0.04), RV strain (ATTR: -21.9% ± 6.2 vs. AL: -16.8% ± 6 P = 0.03) and better reservoir function of the LA strain (ATTR: 22% ± 12 vs. AL: 13.6% ± 7.8 P = 0.02). Cut-off points were calculated based on the Youden method. We attributed to 2 points for parameters having an AUC > 0.75 (NT-proBNP AUC 0.799; hs-cTnI AUC 0.87) and 1 point for GFR (AUC 0.749) and TTE parameters (GLS AUC 0.666; RV FWS AUC 0.649, LASr AUC 0.643). A score of equal or more than 4 points has been able to differentiate between AL and ATTR (sensitivity 80%, specificity 62%, AUC = 0.798). The differential diagnosis score system was applied to the validation cohort of 52 CA patients showing a sensitivity of 81% with specificity of 77%.

CA is a complex entity and requires extensive testing for a positive diagnosis. This study highlights a series of non-invasive checkpoints, which can be useful in guiding the decision-making process towards a more accurate and rapid differential diagnosis.

Morbidity and mortality of patients with immunoglobulin light chain (AL) amyloidosis are strongly associated with the severity of cardiac involvement, especial in patients with cardiac stage IIIb, but the real-world data on these patients is still limited.

A retrospective analysis was conducted on 77 patients diagnosed with cardiac stage IIIb AL amyloidosis at our center. We analyzed the clinical characteristics, treatment and outcome of the patients.

The median age of patients was 57 years and 49.4% were male. Median serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) were 13,384 ng/L and 0.166 ug/L, and 42 (54.5%) patients had heart failure at diagnosis. Fifty-seven (74.0%) patients received antiplasma cell treatment, and the main treatment options include bortezomib or thalidomide combined with dexamethasone. The hematologic overall response rate was 70% (28/40), and at 6-month landmark analysis, patients with hematologic responses had a higher survival rate. Cardiac and renal responses were achieved in 14 (37.8%) and 13 (32.5%) patients, respectively. After a median follow-up of 10 months (range 1-115 months), median overall survival (OS) was 18 months, and the estimated survival rates at 3, 6, and 12 months were 79.9%, 75.6%, and 54.5%, respectively. In Cox regression models, age, hypotension and cTnT were independently predictive of mortality after adjusting for heart failure.

The hematologic, cardiac and renal responses were relative lower in patients with cardiac stage IIIb AL amyloidosis. The overall prognosis of patients was poor, and age, hypotension, and cTnT can be used to predict mortality.

To evaluate different cardiovascular magnetic resonance (CMR) parameters for the differentiation of light chain amyloidosis (AL) and transthyretin-related amyloidosis (ATTR).

In total, 75 patients, 53 with cardiac amyloidosis {20 patients with AL [66 ± 12 years, 14 males (70%)] and 33 patients with ATTR [78 ± 5 years, 28 males (88%)]} were retrospectively analysed regarding CMR parameters such as T1 and T2 mapping, extracellular volume (ECV), late gadolinium enhancement (LGE) distribution patterns, and myocardial strain, and compared to a control cohort with other causes of left ventricular hypertrophy {LVH; 22 patients [53 ± 16 years, 17 males (85%)]}. One-way ANOVA and receiver operating characteristic analysis were used for statistical analysis. ECV was the single best parameter to differentiate between cardiac amyloidosis and controls [area under the curve (AUC): 0.97, 95% confidence intervals (CI): 0.89-0.99, P < 0.0001, cut-off: >30%]. T2 mapping was the best single parameter to differentiate between AL and ATTR amyloidosis (AL: 63 ± 4 ms, ATTR: 58 ± 2 ms, P < 0.001, AUC: 0.86, 95% CI: 0.74-0.94, cut-off: >61 ms). Subendocardial LGE was predominantly observed in AL patients (10/20 [50%] vs. 5/33 [15%]; P = 0.002). Transmural LGE was predominantly observed in ATTR patients (23/33 [70%] vs. 2/20 [10%]; P < 0.001). The diagnostic performance of T2 mapping to differentiate between AL and ATTR amyloidosis was further increased with the inclusion of LGE patterns [AUC: 0.96, 95% CI: (0.86-0.99); P = 0.05].

ECV differentiates cardiac amyloidosis from other causes of LVH. T2 mapping combined with LGE differentiates AL from ATTR amyloidosis with high accuracy on a patient level.

Cardiac amyloidosis, increasingly recognized for its significant impact on global heart health and patient survival, demands a thorough review to understand its complexity and the urgency of improved management strategies. As a cause of cardiomyopathy and heart failure, particularly in patients with aortic stenosis and atrial fibrillation, this condition also relates to higher incidences of dementia in the affected populations. The objective of this review was to integrate and discuss the latest advancements in diagnostics and therapeutics for cardiac amyloidosis, emphasizing the implications for patient prognosis. We evaluated the latest literature from major medical databases such as PubMed and Scopus, focusing on research from 2020 to 2024, to gather comprehensive insights into the current landscape of this condition. Insights from our review highlight the complex pathophysiology of cardiac amyloidosis and the diagnostic challenges it presents. We detail the effectiveness of emerging treatments, notably gene silencing therapies like patisiran and vutrisiran, which offer transformative potential by targeting the production of amyloidogenic proteins. Additionally, the stabilization therapy acoramidis shows promise in modifying disease progression and improving clinical outcomes. This review underscores the critical need for updated clinical guidelines and further research to expand access to groundbreaking therapies and enhance disease management. Advocating for continued research and policy support, we emphasize the importance of advancing diagnostic precision and treatment effectiveness, which are vital for improving patient outcomes and addressing this debilitating disease globally.

Hereditary transthyretin amyloidosis (ATTRv) is a rare, progressive, and life-threatening disease caused by misfolded transthyretin (TTR) proteins that aggregate as abnormal amyloid fibrils and accumulate throughout the body. The kidney is one of the main organs affected in amyloid light chain (AL) amyloidosis and ATTRv amyloidosis. The most common clinical presentation is proteinuria, which consists mainly of albumin; this is the first step in the natural history of ATTRv nephropathy. Not all TTR mutations are equal in terms of ATTRv kidney involvement. Kidney involvement in ATTRv itself is difficult to define, given the numerous associated confounding factors. There are several treatments available to treat ATTRv, including orthotopic liver transplant (OLT), which is the classic treatment for ATTRv. However, we should be careful regarding the use of calcineurin inhibitors in the setting of OLT because these can be nephrotoxic. New treatments for amyloidosis may have an impact on kidney function, including drugs that target specific pathways involved in the disease. Tafamidis and diflunisal, which are TTR stabilizers, patisiran (RNA interference agent), and inotersen (antisense oligonucleotide inhibitor) have been shown to reduce TTR amyloid. Tafamidis and patisiran are medications that have reduced the progression of kidney disease in amyloidosis, but inotersen and diflunisal may damage kidney function.

Cardiac amyloidosis is an infiltrative disease primarily caused by extracellular tissue deposition of amyloid fibrils in the myocardial interstitium. The aim of the present review was to summarize findings regarding changes in myocardial mechanics, valvular abnormalities, and vascular remodeling detected in patients with cardiac amyloidosis.

Cardiac amyloidosis is a rare but increasingly recognized condition characterized by the deposition of amyloid fibrils in cardiac tissue, leading to structural and functional heart impairment. This infiltrative cardiomyopathy often mimics more common cardiac conditions, posing significant diagnostic challenges. Particularly deceptive is its presentation as non-ST-segment elevation myocardial infarction (NSTEMI), where the clinical overlap necessitates considering amyloidosis in differential diagnoses. A 75-year-old male presented with muscle weakness, respiratory infection symptoms, and elevated cardiac enzymes. His history included a recent hospitalization for NSTEMI, with normal coronary angiography. Initial evaluations showed elevated troponin and CRP levels. A comprehensive cardiac assessment revealed a dilated ascending aorta, moderate systolic dysfunction (left ventricular ejection fraction (LV-EF), 47%), and asymmetrical interventricular septal thickening, suggesting hypertrophic cardiomyopathy or amyloidosis. The patient improved and was referred for further specialized care. Cardiac amyloidosis can mimic acute coronary syndrome (ACS), presenting with chest pain and elevated cardiac biomarkers. Differentiation is critical as amyloidosis involves myocardial infiltration by amyloid proteins, leading to restrictive cardiomyopathy. Advanced imaging techniques like cardiac MRI and nuclear scintigraphy are essential for accurate diagnosis and appropriate management, impacting therapeutic strategies and patient outcomes.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is an infiltrative disease of the myocardium in which extracellular deposits of amyloid cause progressive cardiac impairment. We aimed to evaluate left atrial (LA) deformation and its association with left ventricular (LV) deformation using LA-LV strain loops in patients with ATTR-CM and patients with LV hypertrophy (LVH). We hypothesized that LA strain in ATTR-CM patients is abnormal and more independent of LV strain, compared to LVH patients.

Retrospective study based on echocardiographic data including 30 patients diagnosed with ATTR-CM based on an end-diastolic interventricular septal (IVSd) thickness of ≥14 mm, and 29 patients with LVH (IVSd ≥ 14 mm and no ATTR-CM diagnosis) together with 30 controls. LV global longitudinal strain (LV-GLS) and LA strain, assessed as peak atrial longitudinal strain (PALS), were acquired and plotted to construct LA-LV strain loops and used regression line to determine a LA-LV strain slope. Significantly lower PALS and LA-LV strain slope values were detected in ATTR-CM patients compared to LVH patients (P = 0.004 and P = 0.014, respectively). A receiver operating characteristic (ROC) curve demonstrated similar area under the curve (AUC) using PALS (AUC 0.72) and LA-LV slope (AUC 0.71), with both resulting in higher values than recorded for LV-GLS (AUC 0.62).

LA deformation demonstrates an independent ability to differentiate ATTR-CM from LVH. Combining LV strain and LA deformation analysis displays the mechanical LA-LV dissociation in ATTR cardiac amyloidosis and potentially unmasks LA amyloid infiltration; this could potentially enable quicker diagnosis and initiation of treatment for ATTR-CM.

Tafamidis is the first drug approved by the European Commission for the treatment of wild-type or hereditary transthyretin amyloid cardiomyopathy (ATTR-CM) in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization. Real-world treatment patterns of tafamidis 61 mg in Germany are not well studied in patients with ATTR-CM.

This was a non-interventional, retrospective, observational cohort study of adult patients in Germany based on the IQVIA pharmacy claims database (IQVIA™ LRx). Patients included in the analysis were statutory insured and received at least one prescription of tafamidis 61 mg between March 1, 2020 and August 31, 2022. Treatment adherence was analyzed using the modified medical possession ratio (mMPR) and proportion of days covered (PDC).

Overall, 1565 adult patients received at least one tafamidis prescription in the study period. Their mean age was 78.3 years, 82.4% were male, and 23.2% were treated by a cardiologist. Persistency rates for patients treated with tafamidis 61 mg were high: 78.0% for 12 months and 65.1% for 24 months after treatment initiation. Patients also had high adherence rate on filling their prescriptions on time: 94.6% and 90.5% of patients had adherence rates of at least 80%, measured by mMPR and PDC, respectively.

In the IQVIA™ LRx database, patients prescribed tafamidis 61 mg in Germany displayed high adherence and persistency rates, which suggest good drug tolerability and ease of use.

Alcohol septal ablation (ASA) has been widely used in relieving the left ventricular outflow tract (LVOT) obstruction caused by hypertrophic obstructive cardiomyopathy (HOCM). There is limited data about the utility of ASA in cases of cardiac amyloidosis with LVOT obstruction. Our patient is 71-year-old male with a history of multiple myeloma complicated by cardiac amyloidosis and end-stage renal disease on hemodialysis who presented from the dialysis center due to hypotension. The patient was admitted to our hospital for further workup. He underwent echocardiography that showed severely elevated LVOT gradient pressures and the decision was made to proceed with ASA, which led to significant improvement in the LVOT gradient pressures and the patient being able to tolerate his dialysis sessions.

The purpose of this study is to investigate the drug safety of three Transthyretin (TTR) inhibitors in the real world using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database.

This study extracted reports received by the FAERS database from the first quarter of 2018 to the third quarter of 2023 for descriptive analysis and disproportionality analysis. Safety signal mining was conducted at the Preferred Term (PT) level and the System Organ Class (SOC) level using reporting odds ratio (ROR). The characteristics of the time-to-onset curves were analyzed using the Weibull Shape Parameter (WSP). The cumulative incidence of TTR inhibitors was evaluated using the Kaplan-Meier method. Subgroup analyses were conducted based on whether the reporter was a medical professional.

A total of 3,459 reports of adverse events (AEs) caused by TTR inhibitors as the primary suspect (PS) drug were extracted. The top three reported AEs for patisiran were fatigue, asthenia, and fall, with the most unexpectedly strong association being nonspecific reaction. The top three reported AEs for vutrisiran were fall, pain in extremity and malaise, with the most unexpectedly strong association being subdural haematoma. The top three reported AEs for inotersen were platelet count decreased, blood creatinine increased, and fatigue, with the most unexpectedly strong association being blood albumin decreased. Vitamin A decreased, arthralgia, and dyspnea were the same AEs mentioned in the drug labels of all three drugs, while malaise and asthenia were the same unexpected significant signals. This study offers evidence of the variability in the onset time characteristics of AEs associated with TTR inhibitors, as well as evidence of differences in adverse event reporting between medical professionals and non-medical professionals.

In summary, we compared the similarities and differences in drug safety of three TTR inhibitors in the real world using the FAERS database. The results indicate that not only do these three drugs share common AEs, but they also exhibit differences in drug safety profiles. This study contributes to enhancing the understanding of medical professionals regarding the safety of TTR inhibitors.

In recent years, the interest in cardiac amyloidosis has grown exponentially. However, there is a need to improve our understanding of amyloidosis in order to optimise early detection systems. Therefore, it is crucial to incorporate solutions to improve the suspicion, diagnosis and follow-up of cardiac amyloidosis. In this sense, we designed a tool following the different phases to reach the diagnosis of cardiac amyloidosis, as well as an optimal follow-up: a) clinical suspicion, where the importance of the "red flags" to suspect it and activate the diagnostic process is highlighted; 2) diagnosis, where the diagnostic algorithm is mainly outlined; and 3) follow-up of confirmed patients. This is a practical resource that will be of great use to all professionals caring for patients with suspected or confirmed cardiac amyloidosis, to improve its early detection, as well as to optimise its accurate diagnosis and optimal follow-up.

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.

Introduction. Cardiac amyloidosis is a lethal disease, the incidence of which is increasing every year. Early diagnosis and treatment are the keys to reducing the mortality of this disease. Methods. Relevant English literature published in Embase, PubMed, Cochrane Library, and Web of Science were searched until December 1, 2022. Meta-analysis was performed with Stata 17.0 software. Results. A total of 1060 patients with 5 articles were included in this study. The sensitivity of abdominal fat aspiration biopsy for the diagnosis of cardiac amyloidosis was 0.66 (0.48-0.84) and the sensitivity for light chain amyloidosis cardiomyopathy and transthyretin amyloidosis cardiomyopathy was 0.90 (0.80-0.97) and 0.39 (0.18-0.60), respectively. Conclusion. Abdominal fat aspiration biopsy has high sensitivity and clinical value in the diagnosis of light chain amyloidosis cardiomyopathy, whereas there are limitations in the diagnosis of transthyretin amyloidosis cardiomyopathy.

The early diagnosis of cardiac amyloidosis (CA) is paramount, since there are effective therapies that improve patient survival. The diagnostic accuracy of classical electrocardiographic (ECG) signs, such as low voltage, pseudoinfarct pattern, and conduction disturbances in the diagnosis of CA, is inferior to that of the echocardiographic myocardial deformation criteria; therefore, our aim was to find more accurate novel ECG criteria for this purpose.

We tested the diagnostic value of five novel ECG criteria, two of them devised by us, in 34 patients with confirmed CA (20 transthyretin amyloidosis and 14 AL amyloidosis) and 45 control patients with left ventricular hypertrophy on echocardiography due to hypertension, valvular aortic stenosis and hypertrophic cardiomyopathy. The following novel ECG criteria, that suggested CA, were tested: QRS amplitude in lead I < 0.55 mV (I < 0.55); QRS amplitude in lead aVR < 0.5 mV (aVR < 0.5); average QRS amplitude of leads I + aVR < 0.575 mV [(I + aVR) < 0.575]; average QRS amplitude of leads I + aVR/average QRS amplitude of leads V1-4 < 0.375 [(I + aVR)/(V1-4) < 0.375]; average QRS amplitude of leads I + aVR/longest intrinsicoid deflection in leads I,aVL,V1-6 < 0.0115 [(I + aVR)/I,aVL,V1-6ID < 0.0115].

The I < 0.55, aVR < 0.5, (I + aVR) < 0.575, (I + aVR)/(V1-4) < 0.375, (I + aVR)/I,aVL,V1-6ID < 0.0115 test accuracy (TA) were 81%, 84.8%, 82.3%, 84.8%, and 83.3%, respectively; the sensitivity (SE): 76.5%, 82.4%, 85.3%, 82.4%, and 76.9%; specificity (SP): 84.4%, 86.7%, 80%, 86.7%, and 87.5%; positive predictive values (PPV): 78.8%, 82.4%, 76.3%, 82.4%, and 80%; negative predictive values (NPV): 82.6%, 86.7%, 87.8%, 86.7%, and 85.4%; area under curve (AUC) values: 0.8922, 0.8794, 09016, 0.8824, and 0.8462 were respectively. These parameters of the novel ECG criteria were at least as good as those reported by other authors in the literature of the qualitative (TA: 67%, SE: 80%, SP: 34%, PPV: 75%, NPV: 42%, AUC: 0.57) and quantitative apical sparing (TA: 64-80%, SE: 66-81.3%, SP: 55-78.3%, PPV: 33-83.9%, NPV: 41-75%, AUC: 0.62-0.68) and left ventricular ejection fraction/global longitudinal strain >4.1 (TA: 77%, SE: 93%, SP: 38%, PPV: 79%, NPV: 69%, AUC: 0.65) echocardiographic criteria. Among the classical criteria, the low voltage in limb leads criterion was present most frequently (in 73.5%) in patients with CA, with slightly worse diagnostic value than the novel ECG criteria (TA: 78.5%, SE: 73.5%, SP: 82.2%, PPV: 75.8%, NPV: 80.4%).

The novel ECG criteria [mostly the aVR < 0.5, (I + aVR)/(V1-4) < 0.375] seem at least as reliable in the diagnosis of CA as the best echocardiographic myocardial deformation criteria and might be used either together with the echocardiographic criteria or as stand-alone criteria to diagnose CA in the future.

Infiltrative diseases (IDs), including amyloidosis, sarcoidosis, and hemochromatosis, are characterized by abnormal cellular infiltration in multiple organs, including the heart. The prognosis of percutaneous coronary intervention (PCI) patients with underlying IDs has not been well-studied. We evaluated the prevalence of IDs in patients undergoing PCI and their association with post-PCI outcomes.

The National Inpatient Sample (NIS) 2016-2020 database was used to identify PCI patients with ICD-10 codes for a retrospective analysis. PCI patients were then divided into those with and without underlying IDs, which included amyloidosis, sarcoidosis, and hemochromatosis. Multivariable logistic regression was performed for composite post-PCI outcomes analyses.

Among 2,360,860 patients admitted to undergo PCI, 7855 patients had underlying IDs. The highest prevalence was observed for sarcoidosis (0.2%) followed by hemochromatosis (0.07%) and amyloidosis (0.04%). Underlying amyloidosis was associated with worse composite post-PCI outcomes (odds ratio [OR], 1.6; 95% CI, 1.1-2.44; P = .02), including higher in-hospital mortality (OR, 1.9; 95% CI, 1.1-3.4; P = .04), higher risk of intra/post-PCI stroke (OR, 4.0; 95% CI, 1.1-16.0; P = .04), but not major bleeding (OR, 2.2; 95% CI, 0.97-5.03; P = .058). In contrast, underlying sarcoidosis (OR, 1.1; 95% CI, 0.87-1.41; P = .4), and hemochromatosis (OR, 1.18; 95% CI, 0.77-1.8; P = .44) were not associated with composite post-PCI outcomes. Amyloidosis patients undergoing PCI also had higher hospitalization charges ($212,123 vs $141,137; P = .03) and longer length of stay (8.2 vs 3.9 days; P < .001).

Underlying amyloidosis was associated with worse post-PCI outcomes including higher in-hospital mortality, intra/post-PCI stroke, and socioeconomic burden. A multidisciplinary approach and future studies are needed to investigate the screening and treatment strategies in these patients.

Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) benefit from disease-modifying agents such as tafamidis. However, the survival benefit of tafamidis in elderly patients (age ≥80 years) is not reported. This study aimed to assess the survival of patients with ATTR-CM aged 80 years and older who were treated with tafamidis compared with patients aged <80 years. We conducted a retrospective analysis of patients with ATTR-CM who underwent tafamidis treatment, aged 45 to 97 years at the time of diagnosis between January 1, 2008, and May 31, 2021. A total of 484 patients were included, with 208 in the ≥80 years group and 276 in the <80 years group. The cohort was followed up for mortality outcomes, and hazard ratios with 95% confidence intervals were calculated. After a median follow-up of 18.5 months, 72 deaths were recorded in the entire cohort. Kaplan-Meier curves showed no differences in survival probability between the 2 groups at 30 months (p for log-rank test = 0.76). The survival rates for patients aged ≥80 years who underwent treatment at 1, 2, 3, 4, and 5 years were 94.7%, 86.0%, 77.0%, 77.0%, and 38.5%, respectively. The corresponding rates for patients aged <80 years who underwent treatment were 93.2, 84.8, 74.4, 68.2, and 64.6%, respectively. In the multivariable analysis, the hazard ratio (95% confidence interval) of the mortality comparing treatment patients aged ≥80 years with those aged <80 years was 0.81 (0.41 to 1.61). In conclusion, tafamidis treatment is associated with similar reductions in mortality in older and younger patients with ATTR-CM.