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Heart failure (HF) is a complex syndrome that requires tailored and patient-centered treatment. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) constitute one of the four pillars of the medical treatment of HF. However, the 2023 ESC guidelines treat HF as a single entity without making clear distinctions in phenotypes according to etiology. This creates a "gap in knowledge", causing much debate about the applicability of these drugs in peculiar clinical settings that are etiological and/or predisposing clinical conditions for HF. Furthermore, considering the variety of etiologies and different pathophysiological backgrounds of HF, one might question whether the use of SGLT2is is equally beneficial in all types of HF and whether certain drug-related properties may be exploited in different contexts. For example, SGLT2is can improve the metabolic and inflammatory state, which is fundamental in ischemic heart disease. Anti-inflammatory power can also play a paramount role in myocarditis or cardiotoxicity, while improving the congestive state and reducing filling pressure may be even more fundamental in restrictive heart disease or advanced heart disease. This review aims to gather the evidence currently present in the literature concerning the advantages or the disadvantages of using these drugs in these particular clinical settings, with the goal being an optimized and highly personalized treatment for HF. [ABSTRACT FROM AUTHOR]

Abstract Tafamidis is the world's first and only oral drug approved to treat the rare disease transthyretin amyloid cardiomyopathy (ATTR-CM). Medicines are known to have different adverse reactions during the course of treatment. However, the current limited clinical studies did not identify significant adverse drug reactions to tafamidis. Tafamidis has been on the market for 5 years now, a large number of adverse drug event (ADE) reports with tafamidis as the primary suspected drug have been reported in the United Food and Drug Administration's adverse event reporting system (FAERS). We retrieved 8170 adverse event reports in FAERS with tafamidis as the first suspected drug, and mined these reports for positive signals to perform risk warnings for potentially possible adverse events with tafamidis. We found that a large number of adverse events associated with the primary disease were reported due to insufficient awareness of ATTR among the reporters, leading to a large number of positive signals reported in the cardiac disorders system. We also found that tafamidis has the potential to cause an adverse event risks of ear and labyrinth disorders system and urinary tract infection bacterial, which deserve continued clinical attention.

Amyloid cardiomyopathy (CA) was previously considered a rare disease; however, rapid advancements in imaging modalities have led to an increased frequency of its diagnosis. The aim of this prospective study was to assess the prevalence and clinical phenotype of transthyretin amyloidosis (ATTR) cardiomyopathy in patients exhibiting unexplained increased left ventricular (LV) wall thickness. From 2020 to 2022, we enrolled 100 consecutive adults with unexplained increased LV wall thickness in the study. The analysis included clinical data, electrocardiography, transthoracic echocardiography, single-photon emission computed tomography/computed tomography with 3,3-disphono-1,2-propanodicarboxylic acid, genetic testing. Overall, 18% of patients were diagnosed with CA, comprising 5% with light-chain amyloidosis, and 12% with ATTR. To evaluate associations with the ATTR diagnosis, a LOGIT model and multivariate analysis were applied. Notably, age, polyneuropathy, gastropathy, carpal tunnel syndrome, lumbar spine stenosis, low voltage, ventricular arrhythmia, LV mass, LV ejection fraction, global longitudinal strain (GLS), E/A, E/E′, right ventricle (RV) thickness, right atrium area, RV VTI, TAPSE, apical sparing, ground glass appearance of myocardium, thickening of interatrial septum, thickening of valves, and the "5–5–5" sign were found to be significantly associated with ATTR (p < 0.05). The best predictive model for ATTR diagnoses exhibited an area under the curve of 0.99, including LV mass, GLS and RV thickness. This study, conducted at a cardiology referral center, revealed that a very considerable proportion of patients with unexplained increased LV wall thickness may suffer from underlying CA. Moreover, the presence of ATTR should be considered in patients with increased LV mass accompanied by reduced GLS and RV thickening. [ABSTRACT FROM AUTHOR]

Tafamidis is the world's first and only oral drug approved to treat the rare disease transthyretin amyloid cardiomyopathy (ATTR-CM). Medicines are known to have different adverse reactions during the course of treatment. However, the current limited clinical studies did not identify significant adverse drug reactions to tafamidis. Tafamidis has been on the market for 5 years now, a large number of adverse drug event (ADE) reports with tafamidis as the primary suspected drug have been reported in the United Food and Drug Administration's adverse event reporting system (FAERS). We retrieved 8170 adverse event reports in FAERS with tafamidis as the first suspected drug, and mined these reports for positive signals to perform risk warnings for potentially possible adverse events with tafamidis. We found that a large number of adverse events associated with the primary disease were reported due to insufficient awareness of ATTR among the reporters, leading to a large number of positive signals reported in the cardiac disorders system. We also found that tafamidis has the potential to cause an adverse event risks of ear and labyrinth disorders system and urinary tract infection bacterial, which deserve continued clinical attention. [ABSTRACT FROM AUTHOR]

Cardiac amyloidosis, a condition characterized by abnormal protein deposition in the heart, leads to restrictive cardiomyopathy and is notably associated with an increased risk of arrhythmias and conduction disorders. This article reviews the current understanding and management strategies for these cardiac complications, with a focus on recent advancements and clinical challenges. The prevalence and impact of atrial arrhythmias, particularly atrial fibrillation, are examined, along with considerations for stroke risk and anticoagulation therapy. The article also addresses the complexities of managing rate and rhythm control, outlining the utility and limitations of pharmacological agents and interventions such as catheter ablation. Furthermore, it reviews the challenges in the treatment of ventricular arrhythmias, including the contentious use of implantable cardioverter-defibrillators for primary and secondary prevention. Individualized approaches, considering the unique characteristics of cardiac amyloidosis, are paramount. Continuous research and clinical exploration are essential to refine treatment strategies and improve outcomes in this challenging patient population. [ABSTRACT FROM AUTHOR]

Aim. To evaluate the features of diagnosis of amyloid cardiomyopathy (ACMP), differential diagnosis of different types of amyloidosis and its clinical manifestations. Materials and methods. Were analyzed 150 cases of patients who consulted at the Expert Center for Amyloidosis with suspicion of the presence of ACMP. 63 patients were diagnosed with ACMP: 25 (39.7%) – women, 38 (60.3%) – men, with an average age of 64.1±1.5. 36 (57.1%) patients had AL-amyloidosis (immunoglobulin amyloid light-chain amyloidosis), 25 (39.7%) – ATTR-amyloidosis (transthyretin amyloidosis), 2 (3.2%) – AA-amyloidosis with heart failure (reactive systemic amyloidosis caused by hypersecretion of á-globulin). The analysis of clinical manifestations depending on the type of amyloidosis, data of laboratory and instrumental methods of diagnosis is carried out. Results. In most cases, 53 (84.1%) patients, amyloidosis manifested as signs of heart failure. Among cardiac manifestations, shortness of breath (95.2%), general weakness (93.7%), lower limb edema (76.2%) were the most common. To confirm the diagnosis, despite the high accuracy of the speckle-tracking echocardiography and magnetic resonance imaging of the heart with gadolinium, in rare cases a biopsy is required (e.g. there is a combination of clinical signs of several types of amyloidosis). Biopsy of the affected organ was performed in 31 (49.2%) patients. The strategy for further pathogenetic treatment depends on the determination of the type of amyloidosis. Free light chains of immunoglobulins were detected in 57.1% of cases, which allowed diagnosis of AL-amyloidosis. In 17 (38.6%) patients myocardial scintigraphy with 99mTc-pyrophosphate showed signs of ATTR-amyloidosis, which with a negative result of immunochemical studies allows non-invasive diagnosis of it. Conclusion. ACMP is a disease with an extremely adverse prognosis. Raising the awareness of specialists about ACMP is an important goal. With timely diagnosis, pathogenetic therapy can be started early, which will improve the quality of life and prognosis of patients with ACMP.

• The discordance between ECG and echocardiogram mass is a red flag of amyloid cardiomyopathy and can be measured by numerous ECG/echo indexes • The best performing ECG/echo index among subjects with echocardiographic suspicion of amyloid cardiomyopathy was the ratio between the sum of all QRS voltages and maximum left ventricle wall thickness <7,8 • The best performing ECG/echo index added to a clinical model of few easy-accessible variables greatly increased the diagnostic accuracy for amyloid cardiomyopathy The discordance between QRS voltages on electrocardiogram (ECG) and left ventricle (LV) wall thickness (LVWT) on echocardiogram (echo) is a recognized red flag (RF) of amyloid cardiomyopathy (AC) and can be measured by specific indexes. No head-to-head comparison of different ECG/echo indexes among subjects with echocardiographic suspicion of AC has yet been undertaken. The study aimed at evaluating the performance and the incremental diagnostic value of different ECG/echo indexes in this subset of patients. Electrocardiograms of subjects with LV hypertrophy, preserved ejection fraction and ≥ 1 echocardiographic RF of AC participating in the AC-TIVE study, an Italian prospective multicenter study, were independently analyzed by two cardiologists. Low QRS voltages and 8 different ECG/echo indexes were evaluated. Cohort specific cut-offs were computed. Among 170 patients, 55 (32 %) were diagnosed with AC. Combination of low QRS voltages with interventricular septum ≥ 1,6 cm was the most specific (specificity 100 %, positive predictive value 100 %) ECG/echo index, while the ratio between the sum of all QRS voltages and LVWT <7,8 was the most sensitive and accurate (sensitivity 94 %, negative predictive value 97 %, accuracy 82 %). When the latter index was added to a model using easily-accessible clinical variables, the diagnostic accuracy for AC greatly increased (AUC from 0,84 to 0,95; p = 0,007). Among patients with non-dilated hypertrophic ventricles with normal ejection fraction and echocardiographic RF of AC, easily-measurable ECG/echo indexes, mainly when added to few clinical variables, can help the physician orient second level investigations. External validation of the results is warranted. [Display omitted] [ABSTRACT FROM AUTHOR]

Aims Wild-type transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly recognized condition. It remains challenging to estimate the extent of disease and the prognosis for most patients. Myocardial work is a sensitive echocardiographic approach that improves the characterization of myocardial damage. We investigate the parameters of myocardial deformation and work in ATTR-CM patients and their changes over time. Methods and results We analysed clinical, electrocardiographic, biological, and echocardiographic characteristics in 113 patients [median age 82 (77–85), 90.4% male] diagnosed with wild-type ATTR-CM based on international consensus at a single centre. We compared the data at baseline and 18-month follow-up. Thirty-four patients died and 12 were hospitalized for heart failure at a median follow-up of 935 days (interquartile range 691–1159 days). Left ventricular end-diastolic diameter, left atrial strain during reservoir phase (LASRES), left ventricular longitudinal strain, global work index (GWI), global constructive work significantly decreased from baseline to 18 months, while left ventricular wall thickness increased. Left ventricular ejection fraction, right ventricular free wall strain (FWS), global wasted work (GWW), and global work efficiency did not alter significantly. Strain parameters were identified as prognostic on baseline evaluation using a multivariate analysis: GWI, GWW, FWS, and LASRES. They were significantly associated with the risk of death and hospitalization for heart failure. Conclusion Multi-chamber strain assessment may improve the surveillance of patients with ATTR-CM, and myocardial work parameters may improve clinical risk stratification in this population. [ABSTRACT FROM AUTHOR]

Purpose of Review: The purpose of this review is to summarize currently available and developing diagnostic and treatment options for hereditary transthyretin amyloid polyneuropathy. Transthyretin amyloidosis (ATTR) predominantly manifests with cardiomyopathy and/or peripheral neuropathy, but amyloid deposits may be found in other organs or tissues. Recent Findings: Currently available treatments include transthyretin gene silencers (for hereditary ATTR peripheral neuropathy only) and transthyretin stabilizers (tafamidis for ATTR cardiomyopathy in the USA, and for both hereditary ATTR peripheral neuropathy and ATTR cardiomyopathy in Europe, Japan, Brazil, and some other countries), and liver transplantation. Gene silencers stop the progression of hereditary ATTR peripheral neuropathy in most patients, and transthyretin stabilizers reduce hospitalizations and mortality in patients with ATTR cardiomyopathy. The use of liver transplantation for ATTR has declined with the availability of more effective therapies, and shortage of available allografts. On the horizon are new treatments already in clinical trials including new gene silencers and gene editing agents, new transthyretin stabilizers, and amyloid removal treatments. Summary: Recently approved treatments for ATTR have changed its natural history, and additional medications may get approved in the near future. Early diagnosis is still essential to improve treatment outcomes. New management strategies may include combinations of gene silencers, transthyretin stabilizers, gene editing, and amyloid removal agents, but the cost may become the limiting factor. [ABSTRACT FROM AUTHOR]

The article presents a clinical case describing a complex differential diagnosis of cardiac amyloidosis types and verification of the diagnosis of AL-amyloidosis.

Diagnosis and differential diagnosis of cardiac amyloidosis and hypertrophic cardiomyopathy is difficult in some cases, which is confirmed by the presented clinical observation. The patient A., 67 years old, from the age of 59 for 7 years suffered from arterial hypertension with a maximum blood pressure of 170/100 mmHg, received hypotensive therapy. Myocardial infarction, a history of stroke denies. Since January 2018, at the age of 65, against the background of spontaneous stabilization of blood pressure figures, shortness of breath when climbing to the 2nd floor, lifting weights, suffocation at night, swelling of the shins, feet, in connection with which I turned to a doctor. When examined on an electrocardiogram, a low voltage of QRS complexes in the leads from the extremities was noted, there was no increase in the amplitude of the r wave in V1–3. Echocardiography revealed a thickening of the interventricular septum and the posterior wall of the left ventricle up to 1.9 cm without obstruction of the outlet of the left ventricle, restrictive type of diastolic dysfunction, dilation of the left and right atria, moderate pulmonary hypertension, moderate amount of fluid in the pericardial cavity. Magnetic resonance imaging of the heart revealed a pattern typical of cardiac amyloidosis: diffuse subendocardial contrast of the myocardium of both ventricles in the absence of local contractility disorders, increased myocardial thickness in all segments, hydropericardium. Biopsy of the skin and subcutaneous fat with Congo red staining and polarization microscopy revealed no amyloid deposits. No mutations in the transthyretin gene responsible for transthyretin amyloidosis (ATTR–amyloidosis) were detected during the genetic study. Sequencing of 10 genes encoding myocardial sarcomeric proteins in the MYBPC3 gene revealed a mutation c.3197C >G (p.Pro1066Arg) in a heterozygous state, previously described in patients with hypertrophic cardiomyopathy of Slavic origin. Cascade family screening for the mutation was not carried out due to the fact that the patient did not know the father, the mother died at the age of 75 from heart failure, the only son died from an accident six months before the patient’s treatment. On 15.02.2019, the patient suffered a circulatory arrest with successful resuscitation measures. For the purpose of secondary prevention of sudden cardiac death, a single–chamber cardioverter-defibrillator was implanted on 22.02.2019. Despite the ongoing therapy, the patient died in March 2019. from progressive heart failure. Thus, a clinical case is presented where magnetic resonance imaging suspected amyloid cardiomyopathy, which did not receive morphological confirmation in biopsies of extra–cardiac localization. Hypertrophic cardiomyopathy caused by mutation c.3197C >G (p.Pro1066Arg) in the MYBPC3 gene was confirmed on the basis of clinical and instrumental and molecular genetic methods. The pattern characteristic of cardiac amyloidosis described in this patient with instrumental examination methods may be due to a violation of autophagy processes previously described with a number of mutations in the MYBPC3 gene, which may lead to the accumulation of amyloid-like inclusions in cardiomyocytes. For differential diagnosis of cardiomyopathies in complex cases, endomyocardial biopsy may be required. The possibility of coexistence of genetically determined hypertrophic cardiomyopathy and amyloid heart disease is not excluded.

Abstract Background Recent studies have reported atrial involvement and coexistence of aortic stenosis in transthyretin (ATTR) cardiac amyloidosis (CA). However, pathological reports of extraventricular ATTR amyloid deposits in atrial structures or heart valves are limited, and the clinical implications of ATTR amyloid deposits outside the ventricles are not fully elucidated. Case presentation We report 3 cases of extraventricular ATTR amyloid deposits confirmed in surgically resected aortic valves and left atrial structures, all of which were unlikely to have significant ATTR amyloidosis infiltrating the ventricles as determined by multimodality evaluation including 99mtechnetium-pyrophosphate scintigraphy, cardiac magnetic resonance, endomyocardial biopsy and their mid-term clinical course up to 5 years. These findings suggested that these were extraventricular ATTR amyloid deposits localized in the aortic valve and the left atrium. Conclusions While long-term observation is required to fully clarify whether these extraventricular ATTR amyloid deposits are truly localized outside the ventricles or are early stages of ATTR-CA infiltrating the ventricles, our 3 cases with multimodality evaluations and mid-term follow up suggest the existence of extraventricular ATTR amyloid deposits localized in the aortic valve and left atrial structures.

For several years, there has been a significant increase in the number of patients diagnosed with cardiac amyloidosis. However, there are still difficulties associated with the diagnosis, identifying its type and further treatment of the disease. The diversity of the clinical symptoms, the absence of pathognomonic symptoms make it difficult to diagnose, which leads to the progression of the disease. Heart involvement is the main cause of morbidity and mortality in systemic amyloidosis, regardless of the underlying pathogenesis of amyloid production, and in most cases amyloid cardiomyopathy is clinically manifested by rapidly progressive symptoms of heart failure. The article presents a clinical case of a patient with a hereditary type of systemic transthyretin amyloidosis with the involvement of heart, kidneys, liver, nervous system, and the identified mutation in the TTR gene (p.Y89F) has not been previously described in the Russian Federation.

Abstract Aims Wildtype transthyretin amyloid cardiomyopathy is an under‐recognized cause of heart failure in elderly patients. Transcatheter tricuspid valve repair is a newly emerging therapeutic option for severe tricuspid regurgitation (TR). We present first insights into safety and possible benefits of this procedure in patients with cardiac amyloidosis. Methods and results Eight patients with cardiac non‐hereditary (wildtype) transthyretin (ATTRwt) amyloidosis and severe to torrential TR, undergoing successful transcatheter tricuspid valve repair, were included in the analysis and compared to a control group of 21 patients without cardiac amyloidosis. All patients presented with an advanced stage of amyloid cardiomyopathy. Primary endpoint was reduction in TR at 3 months follow‐up. Secondary endpoints were feasibility, safety, hospitalization or death, clinical improvement, cardiac biomarkers, and structural and functional right heart parameter obtained by echocardiography. Transcatheter tricuspid valve repair resulted in a significant reduction of TR (IV to II, P = 0.008) in all eight patients with cardiac amyloidosis (100%). Device success (amyloidosis 75% vs. control group 86%, P = 0.597) and overall probability of hospitalization or death (amyloidosis 13% vs. control group 25%, P = 0.646) were similar compared with those in the control group at 3 months follow‐up. Transcatheter tricuspid valve repair led to an improvement of New York Heart Association functional class (P = 0.031) and 6 min walking distance (from 313 ± 118 to 337 ± 106, P = 0.012). TR reduction in amyloidosis patients was less extensive compared with that in control group (TR‐reduction 1.6 ± 0.3, P = 0.008 vs. control group 2.3 ± 0.3, P

Abstract While patients with transthyretin cardiac amyloidosis (ATTR‐CA) typically present with concentric or asymmetric hypertrophy, a small percentage of ATTR‐CA is known to present with ‘atypical’ cardiac morphologies such as eccentric hypertrophy or even no hypertrophy. However, detailed report of multimodality assessments of ATTR‐CA with no ventricular hypertrophy is lacking. Herein, we report detailed multimodality assessments of an 81‐year‐old Japanese woman with heart failure and history of carpal tunnel syndrome and lumbar canal stenosis, presenting no ventricular hypertrophy and negative 99mtechnetium‐pyrophosphate scintigraphy, who was eventually diagnosed as having wild‐type ATTR‐CA. Our case highlights the role of multimodality assessments for early diagnosis of ATTR‐CA in patients with atypical cardiac morphologies and also emphasizes the limitations of bone scintigraphy and the importance of considering ATTR‐CA in patients with non‐cardiac manifestations of ATTR amyloidosis.

The article is a set of recommendations for the interpretation of electrocardiography and echocardiography data in patients with suspected amyloidosis of the heart. Amyloid cardiomyopathy is a progressive disease characterized by a detailed picture of congestive heart failure, poor quality of life and poor prognosis. Currently, medications have appeared that can improve the prognosis in patients with amyloidosis of the heart. Therefore, raising awareness of specialists about specific instrumental signs of the disease is an important and urgent task.

Abstract Background Hereditary transthyretin (ATTRv) amyloidosis is a rare, genetically heterogeneous and phenotypically variable systemic disease characterized by deposition of misfolded transthyretin fibrils in various tissues. ATTRv cardiomyopathy and progressive axonal polyneuropathy are the most common manifestations, leading to severe disability and ultimately death within approximately ten years. As disease-modifying treatment options evolve, timely diagnosis and treatment initiation are crucial to prevent rapid disease progression. Case presentation Here, we report on a 73-year old patient initially diagnosed with cardiac wild-type ATTR (ATTRwt) amyloidosis by endomyocardial biopsy. Molecular genetic analysis revealed a novel TTR sequence variant (p.Ala65Val) that is highly likely to be amyloidogenic in light of previously reported TTR mutations and the patient’s clinical presentation and family history. Conclusions Our findings expand the spectrum of known pathogenic TTR mutations and underline the importance of a thorough diagnostic workup in amyloidosis patients including careful genetic testing to avoid misdiagnosis and missing of treatment opportunities and to enable cascade testing and tracking of carriers.

Background: Recent studies have reported atrial involvement and coexistence of aortic stenosis in transthyretin (ATTR) cardiac amyloidosis (CA). However, pathological reports of extraventricular ATTR amyloid deposits in atrial structures or heart valves are limited, and the clinical implications of ATTR amyloid deposits outside the ventricles are not fully elucidated. Case presentation: We report 3 cases of extraventricular ATTR amyloid deposits confirmed in surgically resected aortic valves and left atrial structures, all of which were unlikely to have significant ATTR amyloidosis infiltrating the ventricles as determined by multimodality evaluation including 99mtechnetium-pyrophosphate scintigraphy, cardiac magnetic resonance, endomyocardial biopsy and their mid-term clinical course up to 5 years. These findings suggested that these were extraventricular ATTR amyloid deposits localized in the aortic valve and the left atrium. Conclusions: While long-term observation is required to fully clarify whether these extraventricular ATTR amyloid deposits are truly localized outside the ventricles or are early stages of ATTR-CA infiltrating the ventricles, our 3 cases with multimodality evaluations and mid-term follow up suggest the existence of extraventricular ATTR amyloid deposits localized in the aortic valve and left atrial structures. [ABSTRACT FROM AUTHOR]

Introduction. The relationship between systemic amyloidosis and coronavirus disease 2019 (COVID-19) has not been sufficiently studied to date. This paper presents a case of the persistence of COVID-19 markers in an elderly patient with systemic amyloidosis.Brief description. A 74-year-old patient with heart failure with preserved ejection fraction and type 2 diabetes was repeatedly hospitalized due to decompensated heart failure. Based on the data of protein electrophoresis with immunotyping, biopsy of subcutaneous fat and bone marrow, echocardiographic data, the patient was diagnosed with systemic AL amyloidosis with cardiac involvement. During hospitalizations in April, August and December 2020, positive polymerase chain reaction test for SARS-CoV-2 were obtained, while there were no clinical manifestations of infection for a long time and adequate antibody production.Conclusion. A case report demonstrates multiple SARS-CoV-2 reinfection in a severe comorbid elderly patient, as an unfavorable prognostic factor.

Abstract Cardiac amyloidosis is a debilitating disease associated with poor long‐term survival. Medical or palliative treatment is the usual course of therapy, but patients are often intolerant of conventional heart failure treatment. The current standard of care of sequential heart and bone marrow transplant is usually not feasible for ill or frail patients or in countries with limited organ donors or without transplant programmes. Left ventricular assist devices (LVAD) are not usually offered to these patients due to high peri‐operative risks and risks of suction events with the LVAD in a small left ventricle. We report the 2 year outcome and discuss the challenges faced in the management of our patient with end‐stage heart failure due to cardiac amyloidosis, who was successfully supported with an LVAD using a modified left atrium to aorta implantation technique.

Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is more prevalent than appreciated in the elderly. We present the case of an 88-year-old woman who underwent heart transplantation for ischemic cardiomyopathy and then presented 21 years later with new onset atrial flutter, found on endomyocardial biopsy to have new ATTRwt-CM. (Level of Difficulty: Advanced.)

Aims: Transthyretin amyloid cardiomyopathy (ATTR‐CM) is often assumed to be associated with wild‐type TTR genotype (ATTRwt) in elderly patients (aged ≥70), some of whom are not offered genetic testing. We sought to estimate the prevalence, clinical characteristics and prognostic implications of transthyretin (TTR) variants among elderly patients diagnosed with ATTR‐CM. Methods and results: Data from consecutive patients over 70 years of age diagnosed with ATTR‐CM at the UK National Amyloidosis Centre between January 2010 and August 2022 were retrospectively evaluated. All patients underwent clinical evaluation, biochemical tests, echocardiography and TTR genotyping. The study outcome was all‐cause mortality. The study population consisted of 2029 patients with ATTR‐CM (median age 79 years at diagnosis, 13.5% females, 80.4% Caucasian). Variant ATTR‐CM (ATTRv‐CM) was diagnosed in 20.7% (n = 421) of the study population of whom 327 (77.7%) carried V122I, 47 (11.2%) T60A, 16 (3.8%) V30M and 31 (7.3%) other pathogenic TTR variants. During a median (range) follow‐up of 29 (12–48) months, ATTRv‐CM was associated with increased all‐cause mortality compared to ATTRwt‐CM, with the poorest survival observed in V122I‐associated ATTRv‐CM (p < 0.001). Univariable and multivariable logistic regression analyses in those with ATTR‐CM showed younger age at diagnosis (odds ratio [OR] 0.85 per year, p < 0.001), female sex (OR 2.73, p < 0.001), Afro‐Caribbean ethnicity (OR 65.5, p < 0.001), atrial fibrillation (OR 0.65, p = 0.015), ischaemic heart disease (OR 0.54, p = 0.007), peripheral polyneuropathy (OR 5.70, p < 0.001) and orthostatic hypotension (OR 6.29, p < 0.001) to be independently associated with ATTRv‐CM. Conclusion: Up to 20.7% of elderly patients with ATTR‐CM have a pathogenic TTR variant. These findings support routine sequencing of the TTR gene in all patients with ATTR‐CM regardless of age. [ABSTRACT FROM AUTHOR]

Aims: Wildtype transthyretin amyloid cardiomyopathy is an under‐recognized cause of heart failure in elderly patients. Transcatheter tricuspid valve repair is a newly emerging therapeutic option for severe tricuspid regurgitation (TR). We present first insights into safety and possible benefits of this procedure in patients with cardiac amyloidosis. Methods and results: Eight patients with cardiac non‐hereditary (wildtype) transthyretin (ATTRwt) amyloidosis and severe to torrential TR, undergoing successful transcatheter tricuspid valve repair, were included in the analysis and compared to a control group of 21 patients without cardiac amyloidosis. All patients presented with an advanced stage of amyloid cardiomyopathy. Primary endpoint was reduction in TR at 3 months follow‐up. Secondary endpoints were feasibility, safety, hospitalization or death, clinical improvement, cardiac biomarkers, and structural and functional right heart parameter obtained by echocardiography. Transcatheter tricuspid valve repair resulted in a significant reduction of TR (IV to II, P = 0.008) in all eight patients with cardiac amyloidosis (100%). Device success (amyloidosis 75% vs. control group 86%, P = 0.597) and overall probability of hospitalization or death (amyloidosis 13% vs. control group 25%, P = 0.646) were similar compared with those in the control group at 3 months follow‐up. Transcatheter tricuspid valve repair led to an improvement of New York Heart Association functional class (P = 0.031) and 6 min walking distance (from 313 ± 118 to 337 ± 106, P = 0.012). TR reduction in amyloidosis patients was less extensive compared with that in control group (TR‐reduction 1.6 ± 0.3, P = 0.008 vs. control group 2.3 ± 0.3, P < 0.0001). Furthermore, these patients showed no significant improvement of structural right heart parameters. Conclusions: Transcatheter tricuspid valve repair is a safe and feasible new treatment option in patients with amyloid cardiomyopathy and has the potential to improve TR‐grade and clinical status. However, the benefit appears to be less pronounced compared with patients without cardiac amyloidosis. [ABSTRACT FROM AUTHOR]

While patients with transthyretin cardiac amyloidosis (ATTR‐CA) typically present with concentric or asymmetric hypertrophy, a small percentage of ATTR‐CA is known to present with 'atypical' cardiac morphologies such as eccentric hypertrophy or even no hypertrophy. However, detailed report of multimodality assessments of ATTR‐CA with no ventricular hypertrophy is lacking. Herein, we report detailed multimodality assessments of an 81‐year‐old Japanese woman with heart failure and history of carpal tunnel syndrome and lumbar canal stenosis, presenting no ventricular hypertrophy and negative 99mtechnetium‐pyrophosphate scintigraphy, who was eventually diagnosed as having wild‐type ATTR‐CA. Our case highlights the role of multimodality assessments for early diagnosis of ATTR‐CA in patients with atypical cardiac morphologies and also emphasizes the limitations of bone scintigraphy and the importance of considering ATTR‐CA in patients with non‐cardiac manifestations of ATTR amyloidosis. [ABSTRACT FROM AUTHOR]

Background: Improved imaging modalities contributed to increasing awareness of cardiac amyloidosis. Contemporary data on frequency trends in Germany are lacking. Methods: In a retrospective study using health claims data of a German statutory health insurance, patients with diagnostic codes of amyloidosis and concomitant heart failure between 2009 and 2018 were identified. Results: Prevalence increased from 15.5 to 47.6 per 100,000 person-years, and incidence increased from 4.8 to 11.6 per 100,000 person-years, with a continuous steepening in the slope of incidence trend. In patients with amyloidosis and heart failure age and proportion of men significantly increased, whereas the frequency of myeloma and nephrotic syndrome significantly decreased over time. Median (IQR) survival time after first diagnosis was 2.5 years (0.5–6 years), with a 9% (95% CI 2–15%, p = 0.008) reduced risk of death in the second compared to the first 5 years of observation. In the 2 years prior and 1 year after diagnosis, mean total health care costs were 6568 €, 11,872 € and 21,955 € per person and year. Conclusion: The rise in cardiac amyloidosis has continuously accelerated in the last decade. Considering the adverse outcome and high health care burden, further effort should be put on early detection of the disease to implement available treatment. [ABSTRACT FROM AUTHOR]

Abstract Aims It has been reported that a staging system combining N‐terminal pro‐B‐type natriuretic peptide and high‐sensitivity troponin T (hs‐cTnT) or estimated glomerular filtration rate (eGFR) is useful in patients with wild‐type transthyretin amyloid cardiomyopathy (ATTRwt‐CM). However, these studies were mainly conducted in Western countries, and their usefulness for the Japanese population is unclear. We examined and validated the staging system using hs‐cTnT, eGFR, and B‐type natriuretic peptide (BNP) in Japanese patients with ATTRwt‐CM. Methods and results We retrospectively evaluated 176 patients with ATTRwt‐CM. The cut‐off values of hs‐cTnT and eGFR were selected as 0.05 ng/mL and 45 mL/min/1.73 m2, respectively, based on a previous report. The optimal cut‐off value of BNP was 255.6 pg/mL to predict all‐cause mortality (sensitivity, 75%; specificity, 58%; area under the curve, 0.69; 95% confidence interval [CI], 0.61–0.78; P 0.05 ng/mL) and BNP (>250 pg/mL) and decreased eGFR (

There is a paucity of data regarding the impact of cardiac conduction disease (CD) on clinical outcomes in patients with cardiac amyloidosis (CA). The National Inpatient Sample (NIS) was queried to identify all CA admissions and those with CD using ICD-10 codes from 2016 to 2019. We explored baseline characteristics and used multivariate logistic regression to assess the association between CD and several clinical outcomes during index admission; a p -value of <0.05 was significant. Propensity score matching (PSM) was performed to validate our results. A total of 12,185 patients with CA were identified. Of these, 920 (7.6 %) had CD. The median age of the sample was 72 years (IQR: 64–80). After multivariate adjustment and PSM, the presence of CD in CA was associated with higher odds of ventricular arrhythmias (VA) (aOR = 2.97, 95 % CI 1.78–4.96, p < 0.001), syncope (aOR = 3.44, 95 % CI 1.51–7.83, p = 0.003), and cardiovascular implantable electronic device (CIED) implantation (aOR = 12.86, 95 % CI 5.50–30.04, p < 0.001) but not with sudden cardiac arrest (p = 0.092), acute heart failure (p = 0.060), all-cause in-hospital mortality (p = 0.384), and non-routine discharge in patients admitted for CA (p = 0.271). Although CD was not associated with all-cause in-hospital mortality, there was a significant association with VAs and syncope. Syncope is associated with worse survival in patients with CA. Further studies that prospectively follow patients are needed to determine the true effect of cardiac CD on mortality in patients with CA. [Display omitted] • Conduction system disease is significantly associated with adverse outcomes in cardiac amyloidosis, including arrhythmias and CIED implantation. • In cardiac amyloidosis, conduction disease is associated with the development of heart failure, which might be related to dyssynchrony. • Recognition of cardiac amyloidosis is steadily increasing due to advancements in diagnostic techniques and therapeutic options. [ABSTRACT FROM AUTHOR]

Background: Hereditary transthyretin (ATTRv) amyloidosis is a rare, genetically heterogeneous and phenotypically variable systemic disease characterized by deposition of misfolded transthyretin fibrils in various tissues. ATTRv cardiomyopathy and progressive axonal polyneuropathy are the most common manifestations, leading to severe disability and ultimately death within approximately ten years. As disease-modifying treatment options evolve, timely diagnosis and treatment initiation are crucial to prevent rapid disease progression. Case presentation: Here, we report on a 73-year old patient initially diagnosed with cardiac wild-type ATTR (ATTRwt) amyloidosis by endomyocardial biopsy. Molecular genetic analysis revealed a novel TTR sequence variant (p.Ala65Val) that is highly likely to be amyloidogenic in light of previously reported TTR mutations and the patient's clinical presentation and family history. Conclusions: Our findings expand the spectrum of known pathogenic TTR mutations and underline the importance of a thorough diagnostic workup in amyloidosis patients including careful genetic testing to avoid misdiagnosis and missing of treatment opportunities and to enable cascade testing and tracking of carriers. [ABSTRACT FROM AUTHOR]

Diagnosis and treatment of cardiac amyloidosis have rapidly evolved over the past decade by harnessing mechanisms of disease pathogenesis. Cardiac amyloidosis is caused by myocardial deposition of fibrils formed by misfolded proteins, namely transthyretin (ATTR) and immunoglobulin light chains (AL). Advances in noninvasive imaging have revolutionized diagnosis of ATTR cardiomyopathy (CM). Novel treatments for ATTR-CM utilize a range of therapeutic techniques, including protein stabilizers, interfering RNA, gene editing, and monoclonal antibodies. AL-CM, primarily driven by plasma cell dyscrasias, requires treatment with chemotherapy and consideration for autologous stem cell transplant. These incredible advances aim to improve patient outcomes in cardiac amyloidosis., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Amyloidosis is a group of diseases characterized by accumulation of a protein of a specific fibrillar structure in the interstitium of various organs and tissues. The concept of amyloidosis unites more than 30 different pathophysiological conditions, each of which is based on abnormal synthesis of 30 different precursor proteins. However, 95% of amyloid cardiomyopathies are associated with just two proteins: a protein derived from light chains of immunoglobulins and a protein called transthyretin. Determination of the precursor protein is a cornerstone of management of patients with amyloid cardiomyopathy. Transthyretin is a carrier protein of thyroxine, retinol and other substances, that performs vital functions. For hereditary or age-related reasons, TTR misfolding occurs in the liver. The resulting monomers, entering blood, form toxic intermediate products and amyloid fibrils. Cardiac amyloidosis (or amyloid cardiomyopathy) used to be considered a rare disease. In the recent past, possibilities of therapy for cardiac amyloidosis were limited by prescription of diuretics, mineralocorticoid receptor antagonists and anticoagulants, since other drugs are not tolerated well by patients or are tolerated in minimal doses. Advent of the first drug specific for treatment of transthyretin amyloid cardiomyopathy in Russia increased a need of awareness of ATTR-CM among general practitioners and cardiologists, and introduction of modern diagnostic algorithms for this disease. Timely detection and competent differential diagnosis of ATTR-CM from other types of amyloid cardiomyopathy can play a decisive role in the prognosis of this disease. Tafamidis is a treatment that was shown to reduce mortality and CV-related hospitalization in ATTR-CM patients.

Cardiac amyloidosis is a debilitating disease associated with poor long‐term survival. Medical or palliative treatment is the usual course of therapy, but patients are often intolerant of conventional heart failure treatment. The current standard of care of sequential heart and bone marrow transplant is usually not feasible for ill or frail patients or in countries with limited organ donors or without transplant programmes. Left ventricular assist devices (LVAD) are not usually offered to these patients due to high peri‐operative risks and risks of suction events with the LVAD in a small left ventricle. We report the 2 year outcome and discuss the challenges faced in the management of our patient with end‐stage heart failure due to cardiac amyloidosis, who was successfully supported with an LVAD using a modified left atrium to aorta implantation technique. [ABSTRACT FROM AUTHOR]

Left ventricular hypertrophy, atrial fibrillation and chronic heart failure are often in the practice of a cardiologist. The etiology of these conditions is very important because the correct early treatment. We are presenting a case of a late diagnosis of amyloidosis in a 53-year-old man. Despite the complex therapy, the course of the disease was complicated by the development of bilateral pneumonia, sepsis, disseminated intravascular coagulation and the patient died. Autopsy confirmed the diagnosis of systemic AL-amyloidosis (type Kappa) with massive damage to the heart, kidneys, lungs, liver, spleen, adrenal glands, thyroid gland, pancreas, gastrointestinal tract, subcutaneous fatty tissue and arterial vessels of the bone marrow. Thus, screening for amyloidosis is necessary in idiopathic LV thickening, atrial fibrillation, and heart failure for timely intravital diagnosis and therapy.

Aim: To investigate the prevalence of amyloid cardiomyopathy (AC) and the diagnostic accuracy of echocardiographic red flags of AC among consecutive adult patients undergoing transthoracic echocardiogram for reason other than AC in 13 Italian institutions. Methods and results: This is an Italian prospective multicentre study, involving a clinical and instrumental work‐up to assess AC prevalence among patients ≥55 years old with an echocardiogram suggestive of AC (i.e. at least one echocardiographic red flag of AC in hypertrophic, non‐dilated left ventricles with preserved ejection fraction). The study was registered at ClinicalTrials.gov (NCT04738266). Overall, 381 patients with an echocardiogram suggestive of AC were identified among a cohort of 5315 screened subjects, and 217 patients completed the investigations. A final diagnosis of AC was made in 62 patients with an estimated prevalence of 29% (95% confidence interval 23%–35%). Transthyretin‐related AC (ATTR‐AC) was diagnosed in 51 and light chain‐related AC (AL‐AC) in 11 patients. Either apical sparing or a combination of ≥2 other echocardiographic red flags, excluding interatrial septum thickness, provided a diagnostic accuracy >70%. Conclusion: In a cohort of consecutive adults with echocardiographic findings suggestive of AC and preserved left ventricular ejection fraction, the prevalence of AC (either ATTR or AL) was 29%. Easily available echocardiographic red flags, when combined together, demonstrated good diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Atrial fibrillation and flutter (AF/AFL) are common in transthyretin cardiac amyloidosis (ATTR-CM) which in turn is associated with higher risk of thromboembolism. Detecting AF/AFL may be especially important, but the role of routine ambulatory monitoring in ATTR-CM patients is unclear. The objective is therefore to determine prevalence and outcomes of subclinical AF/AFL on routine ambulatory rhythm monitoring. We report outcomes of an observational study of patients at our Amyloidosis Center with wild-type or variant ATTR-CM diagnosed between 2005 and 2019. Patients without known AF/AFL at baseline had ambulatory ECG monitoring (duration 2–30 days) every 6 months while those with cardiovascular implantable electronic devices (CIEDs) had device interrogations instead. Eighty-four patients with ATTR-CM (mean age 73.5 ± 9.7 years, 94% male) had mean follow-up 2.3 ± 1.9 years. Forty patients (48%) had AF/AFL before ATTR-CM diagnosis. In the remainder, 21 (48%) were subsequently diagnosed with AF/AFL: 10 (48%) based on symptoms, and 11 (52%) by monitoring. Anticoagulation (AC) was started in 9/11 (82%) patients with incidental AF/AFL. Among the entire cohort, stroke occurred in 9 patients (11%): 1 hemorrhagic and 8 ischemic (7 in patients with AF/AFL). No strokes occurred in patients on AC. Almost half of patients in our cohort had AF/AFL diagnosed prior to their ATTR-CM diagnosis. In the remainder, approximately half of AF/AFL diagnoses were established incidentally by routine monitoring, most of whom were promptly anticoagulated. Incidence of stroke was high overall, but no strokes occurred in anticoagulated patients. Optimal frequency and duration of monitoring needs further investigation. • In patients with ATTR-CM subsequently diagnosed with AF/AFL, about half were incidentally via ambulatory monitoring. • Incidental detection of AF/AFL led to anticoagulation in most patients with no strokes in this group. • Routine ambulatory monitoring for AF/AFL should be considered in patients with ATTR-CM. [ABSTRACT FROM AUTHOR]

Aims It has been reported that a staging system combining N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T (hs-cTnT) or estimated glomerular filtration rate (eGFR) is useful in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM). However, these studies were mainly conducted in Western countries, and their usefulness for the Japanese population is unclear. We examined and validated the staging system using hs-cTnT, eGFR, and B-type natriuretic peptide (BNP) in Japanese patients with ATTRwt-CM. Methods and results We retrospectively evaluated 176 patients with ATTRwt-CM. The cut-off values of hs-cTnT and eGFR were selected as 0.05 ng/mL and 45 mL/min/1.73 m², respectively, based on a previous report. The optimal cut-off value of BNP was 255.6 pg/mL to predict all-cause mortality (sensitivity, 75%; specificity, 58%; area under the curve, 0.69; 95% confidence interval [CI], 0.61–0.78; P < 0.001) based on a receiver operating characteristic curve. We defined the cut-off value of BNP as 250 pg/mL. Increased hs-cTnT (>0.05 ng/mL) and BNP (>250 pg/mL) and decreased eGFR (<45 mL/min/1.73 m2 ) were significant predictors of poor prognosis (P < 0.05). We calculated the score by adding 1 point if hs-cTnT and BNP levels increased or eGFR decreased by more than the cut-off value. The hazard ratio of all-cause death adjusted by age and sex, using score 0 as a reference, was 0.44 (95% CI 0.08–2.49, P = 0.44) for score 1, 3.69 (95% CI 1.21–11.21, P = 0.02) for score 2, and 5.40 (95% CI 1.57–18.54, P = 0.007) for score 3. We divided patients into a low score group (0–1 point) and high score group (2–3 points). Kaplan–Meier analyses revealed significant differences in all-cause death and rehospitalization for heart failure (log rank test; P < 0.001), and after adjusting for sex and age, the hazard ratio of all-cause death was 6.96 (95% Cl 2.88–16.83, P < 0.001) and that for rehospitalization for heart failure was 4.27 (95% Cl 2.26–8.07, P < 0.001) in the high-risk group, compared with those in the low-risk group. The median survival period was 32.0 months in the high-risk group. Conclusions This simple staging system, which combines hs-cTnT, BNP, and eGFR, was useful for predicting prognosis in Japanese patients with ATTRwt-CM. This system can objectively evaluate the disease progression of ATTRwt-CM and may be useful for patient selection for disease-modifying therapy. [ABSTRACT FROM AUTHOR]

V122I genotype variant (pV142I) is the most common hereditary transthyretin amyloidosis (hATTR) in the USA, with 3–3.5% of African-Americans being the carriers of this mutation. We aimed to compare baseline clinical features, cardiac parameters, and mortality in V122I-ATTR with the wild-type ATTR and other hATTR subtypes. We systematically searched PubMed/Medline and Google Scholar databases to identify relevant studies from inception to 10th September, 2020 reporting phenotypic, echocardiographic, and/or laboratory parameters in patients with hereditary and wild types of cardiac amyloidoses. A total of 2843 patients from 7 individual studies with 67–100% males and an overall follow-up duration of 51.6 ± 30.4 months were identified. The mean age of diagnosis among wild-type ATTR patients was 77 years, followed by 71.2 and 65 years in V122I and T60A group patients, respectively. V122I patients were mostly black, had a poor quality of life, and highest mortality risk compared with other subtypes. Merely, the presence of V122I mutation was identified as an independent predictor of mortality. V30M subtype correlated with the least severe cardiac disease and a median survival duration comparable with T60A subtype. V122I ATTR is an aggressive disease, prevalent in African-Americans, and is associated with a greater morbidity and mortality, which is partly attributed to its misdiagnosis and/or late diagnosis. Current advances in non-invasive studies to diagnose hATTR coupled with concurrent drug therapies have improved quality of life and provide a survival benefit to these patients. [ABSTRACT FROM AUTHOR]

Cardiac amyloidosis (amyloid cardiomyopathy) is a disease damage to the heart caused by extracellular amyloid deposition. In some cases, there may be local damage to the structures of the heart, for example, the atria; more often, heart damage is part of a systemic (generalized) pathology. Depending on the amyloid precursor protein, 36 types of amyloidosis are described, among which hereditary and acquired forms are distinguished. Cardiac amyloidosis is diagnosed 1) in the case of the amyloid infiltration in the myocardial bioptates or 2) in the case of non-cardiac amyloid deposition and the left ventricular wall thickening >12 mm without arterial hypertension and other reasons. The heart is most often affected in AL-, ATTR-, AA-, AANF-types of amyloidosis. Cardiac amyloidosis should be considered in patients with a heart failure with an unclear etiology, especially with preserved left ventricular ejection fraction, refractory to treatment, with proteinuria and CKD 4-5, in patients with idiopathic atrial fibrillation and conduction disturbances, in patients with left ventricular wall thickening of unclear etiology, low ECG voltage, unexplained arterial hypotension and pulmonary hypertension. Screening for cardiac amyloidosis should include non-invasive methods such as electrophoresis and immunofixation of blood and urine proteins, the free light lambda and kappa chains of immunoglobulins, 99Tc-DPD scintigraphy, genetic testing (if hereditary variants of amyloidosis are suspected), as well as a histological examination of biopsy samples stained with Congo red and polarizing microscopy.

Amyloidosis is a unique group of disorders caused by the insoluble protein fibers accumulation known as amyloid fibrils in extracellular tissue and organ spaces. The involvement of different organs and tissues in amyloidosis is often the cause of missed or delayed diagnosis, and amyloidosis remains a major clinical problem as it is associated with 1/1,000 deaths in developed countries. We present a case of a 59-year-old female patient with complaints of breath shortness while talking, a sense of air lack in the horizontal position, swelling of the lower limbs, reduction of blood pressure to a minimum of 70/50 mm Hg, weight reduction by 7 kg in 6 months, dizziness. The patient was hospitalized to the Cardiology Department of Scientific Research Institute – Ochapovsky Regional Clinical Hospital no. 1 with heart failure. The electrocardiogram revealed left ventricular hypertrophy. Echocardiography showed biventricular myocardial hypertrophy with a maximum interventricular septum thickness of 16 mm, nonuniform ventricular myocardial structure and reduction of global left ventricular comparability to 38%. Computer tomography of chest organs demostrated interstitial swelling of parenchyma of both lungs. The infection during the further examination. For the final morphological verification of the diagnosis, it was necessary to perform peripheral transbronchial biopsy S 3, 4, 5 of the left lung and myocardial biopsy with specific staining on amyloid using congo red. In the lung and myocardial biopsy, the colour of the congo red is positive. An immunohistochemical study of the lung tissue and myocardial sample revealed Amyloid AA expression. This case represents a rare cause of heart failure in a woman. A feature of this observation is the rare involvement in the pathological process of both pulmonary tissue and myocardium with AA-amyloid deposition.

Abstract Background In Argentina, there is limited data of prevalence of variant transthyretin amyloidosis (ATTRv) and phenotype‐genotype correlation. The laboratory of Hospital Italiano de Buenos Aires (HIBA) is a reference center for transthyretin (TTR) gene sequencing. The Institutional Amyloidosis Registry (RIA) enable us to characterize people with ATTRv. Our aim was to describe the prevalence of TTR mutations at a reference center in Argentina and the phenotypic presentations of patients with ATTRv included in an institutional registry. Methods Retrospective cohort study of consecutive patients with genetic variants in the TTR gene identified from 2012 to 2019 in the laboratory. We collected all phenotypic characteristics of patients who were clinically evaluated by HIBA doctors. Results Five hundred seventy‐six patients tested, 141 positive: p.Val50Met 107, p.Thr80Ala 16, p.Ala117Ser 9, p.Phe84Leu 2, p.Ile127Val 2, p.Tyr134Cys 2, p.Ala56Pro 2, p.Val142Ile 1. Only 20 patients were clinically evaluated. The mean age at diagnosis was 54 years; 70% had family history with a pedigree median of 4. Mutations were p.Thr80Ala 9, p.Val50Met 6, p.Ala56Pro 2, p.Val142Ile 1, p.Phe84Leu 1, and p.Tyr134Cys 1. Eleven patients presented polyneuropathy, 11 had gastrointestinal compromise, six patients had autonomic compromise, six presented cardiac symptoms and four patients presented ocular involvement. Conclusion We present the first prevalence report of TTR mutations in a reference center of amyloidosis in Argentina. The most frequent genetic variant was p.Val50Met. Our data show considerable phenotypic heterogeneity in the patients with ATTRv.

Background: In Argentina, there is limited data of prevalence of variant transthyretin amyloidosis (ATTRv) and phenotype‐genotype correlation. The laboratory of Hospital Italiano de Buenos Aires (HIBA) is a reference center for transthyretin (TTR) gene sequencing. The Institutional Amyloidosis Registry (RIA) enable us to characterize people with ATTRv. Our aim was to describe the prevalence of TTR mutations at a reference center in Argentina and the phenotypic presentations of patients with ATTRv included in an institutional registry. Methods: Retrospective cohort study of consecutive patients with genetic variants in the TTR gene identified from 2012 to 2019 in the laboratory. We collected all phenotypic characteristics of patients who were clinically evaluated by HIBA doctors. Results: Five hundred seventy‐six patients tested, 141 positive: p.Val50Met 107, p.Thr80Ala 16, p.Ala117Ser 9, p.Phe84Leu 2, p.Ile127Val 2, p.Tyr134Cys 2, p.Ala56Pro 2, p.Val142Ile 1. Only 20 patients were clinically evaluated. The mean age at diagnosis was 54 years; 70% had family history with a pedigree median of 4. Mutations were p.Thr80Ala 9, p.Val50Met 6, p.Ala56Pro 2, p.Val142Ile 1, p.Phe84Leu 1, and p.Tyr134Cys 1. Eleven patients presented polyneuropathy, 11 had gastrointestinal compromise, six patients had autonomic compromise, six presented cardiac symptoms and four patients presented ocular involvement. Conclusion: We present the first prevalence report of TTR mutations in a reference center of amyloidosis in Argentina. The most frequent genetic variant was p.Val50Met. Our data show considerable phenotypic heterogeneity in the patients with ATTRv. [ABSTRACT FROM AUTHOR]

Background: Percutaneous mitral valve repair (PMVR) is a therapeutic option for severe mitral regurgitation (MR) in patients with heart failure due to differential aetiologies. However, only little is known about the safety and efficacy of this procedure in patients with amyloid cardiomyopathy. Methods: Five patients with cardiac amyloidosis and moderate to severe or severe MR undergoing PMVR were analysed retrospectively and compared to seven patients with cardiac amyloidosis and severe MR without intervention. Clinical and functional data, renal function and cardiac biomarkers as well as established risk scores for cardiac amyloidosis were assessed. Primary endpoint was the reduction in MR one year after PMVR. Secondary endpoints were safety, overall mortality after 12 months compared with the control group, as well as changes in clinical and functional parameters. Results: Amyloidosis risk assessment documented amyloid cardiomyopathy at an advanced stage in all patients. Procedural, technical and device success of PMVR were all 100% and residual MR remained mild to moderate at 12 months follow‐up (P =.038 vs before PMVR). Differences in survival compared with the control (no PMVR) group pointed to a possible survival benefit in the PMVR group (P =.02). Conclusion: PMVR is a feasible and safe procedure in patients with cardiac amyloidosis and might carry a possible survival benefit in this patient group. [ABSTRACT FROM AUTHOR]

Competing Interests: Medtronic gave T.O. a lecturing fee. Y.S. received scholarship funds from Medtronic. The remaining authors have no conflicts to disclose.

Amyloidosis refers to a heterogeneous group of disorders sharing common pathophysiological mechanisms characterized by the extracellular accumulation of fibrillar deposits consisting of the aggregation of misfolded proteins. Cardiac amyloidosis (CA), usually caused by deposition of misfolded transthyretin or immunoglobulin light chains, is an increasingly recognized cause of heart failure burdened by a poor prognosis. CA manifests with a restrictive cardiomyopathy which progressively leads to biventricular thickening, diastolic and then systolic dysfunction, arrhythmias, and valvular disease. The pathophysiology of CA is multifactorial and includes increased oxidative stress, mitochondrial damage, apoptosis, impaired metabolism, and modifications of intracellular calcium balance., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Amyloidosis is a heterogeneous group of the diseases caused by the extracellular deposition of amyloid in various organs including a cardiovascular system.Aim. To study the cardiovascular damage in patients with systemic amyloidosis.Material and methods. A retrospective assessment of 38 cases of systemic amyloidosis was carried out. Diagnosis was verified by biopsy in 57,9% (27,3% of these cases were then confirmed by autopsy) and autopsy in 42,1% of patients. Congo red stain and polarized-light microscopy were used. The systemic nature of lesion was diagnosed in the positive biopsies of two or more localizations or in the positive biopsy of one localization in the combination with the clinical picture of amyloidosis at least one organ. Median (interquartile range) of age was 72,5 (64-84) years (women, 65,8%; men, 34,2%).Results. In the medical history, 81,6% of patients with systemic amyloidosis had hypertension, 52,6% — coronary artery disease, 34,2% — myocardial infarction, 36,8% — type 2 diabetes, 44,7% — atrial fibrillation, 26,3% — conduction disorders. Also 13,2% of patients had an implanted pacemaker. According to the electrocardiography, 42,3% of patients had a low QRS voltage. According to echocardiography, left ventricular (LV) hypertrophy was detected in 94,7% of patients. In addition, 31,6% of patients had signs of granular sparkling myocardial appearance, 20% — impaired local LV contractility, 77,8% — increased pulmonary artery reassure, 28,6% — LV diastolic dysfunction, 14,3% — normal diastolic function. LV ejection fraction (LVEF) was 55 (44,5-55)%. LVEF 50% — in 65% of patients. Heart failure was indicated in 71,1% of patients with systemic amyloidosis, chronic kidney disease (CKD) — in 95% of patients. The estimated glomerular filtration rate (CKD-EPI) was 21,2 (13,1-40) ml/min/1,73 m2. Proteinuria (1,1 (0,5-3,0) g/l) was detected in 88,9% of patients. Nephrotic syndrome occurred in 27,8% of patients.Conclusion. Patients with cardiovascular lesions of unclear etiology, especially in the presence of LV wall thickening, preserved LVEF, stage 4-5 CKD and proteinuria, require screening for systemic amyloidosis.

A rare observation of systemic AL-amyloidosis with a debut in old age, accompanied by diffuse alveolar-septal lesion of the lungs and mediastinal lymphadenopathy in combination with amyloid cardiomyopathy in the absence of pathology of kidney and liver function.

Amyloidosis is a heterogeneous group of diseases characterized by the deposition of amyloid. It is caused by extracellular deposition of insoluble fibrils with beta-pleated sheet configuration. The protein misfolding abnormalities result in amyloid fibrils and may manifest as primary, secondary, or familial amyloidosis. Amyloid deposition can occur in multiple organs (eg, heart, liver, kidney, skin, eyes, lungs, nervous system) resulting in a variety of clinical manifestations. Cardiac involvement can occur as part of a systemic disease or as a localized phenomenon. Cardiac involvement in all types of amyloidosis represents a major negative prognostic factor. Early diagnosis, multi-disciplinary cooperation and proper therapy are key aspects of care for patients with amyloid cardiomyopathy. Early diagnosis is crucial, especially in AL amyloidosis, as patients with advanced heart disease are unsuitable candidates for modern, effective hematological treatment including autologous stem cell transplantation. Despite signal development in diagnostics and therapy, the prognosis for patients with advanced cardiac involvement remains poor. This article is an overview of amyloidosis, providing information about the characteristics of cardiac amyloidosis, and present a structured approach to diagnosis, treatment and prognosis of this condition.