Transthyretin amyloidosis prevalence and characteristics in Korean patients with heart failure with preserved or mildly reduced ejection fractions.

The diagnosis and awareness of transthyretin amyloidosis cardiomyopathy (ATTR-CM) in heart failure with left ventricular ejection fraction (LVEF) > 40% remains under-recognized. This study aimed to investigate the prevalence and characteristics of ATTR-CM in patients with heart failure with LVEF > 40%. Patients with LVEF > 40% and maximal left ventricular wall thickness (MWT) > 10 mm who underwent bone scintigraphy were retrospectively investigated. Patients with a definite cause of heart failure were excluded. ATTR-CM was diagnosed when grade 2 or 3 myocardial uptake was observed on scintigraphy. Among 97 patients (male, 62.5%; median age, 69 years), 13 (13.4%) were diagnosed with ATTR-CM (wild type, 69.2%; hereditary type, 30.8%). Age or biomarker levels did not differ significantly; however, all patients with ATTR-CM were male. The ATTR-CM group had a significantly higher prevalence of polyneuropathy or carpal tunnel syndrome than the non-ATTR-CM group, accompanied by a longer PR interval, thicker MWT, larger left atrial volume index, and higher E/e'. Accordingly, ATTR was present in a substantial number, particularly among men. Clinicians should suspect ATTR when a male patient exhibits neurologic symptoms, diastolic dysfunction, and a long PR interval.

[Prevalence of transthyretin cardiac amyloidosis in patients hospitalized for heart failure with preserved ejection fraction and septal thickness]. / Prevalencia de amiloidosis cardíaca por transtiretina en pacientes internados por insuficiencia cardíaca con fracción de eyección preservada y engrosamiento septal.

INTRODUCTION: Transthyretin cardiac amyloidosis (ATTR-CM) usually presents as heart failure with preserved ejection fraction. Its diagnosis has a significant clinical impact, as specific treatment is currently available. The aim of this study is to assess the prevalence of ATTR-CM in patients hospitalized for heart failure with preserved ejection fraction and septal thickness in our region. METHODS: Cross-sectional study. Patients over 18 years old hospitalized for heart failure with preserved ejection fraction (greater than 50%) and septal thickness greater than or equal to 12 mm during the period from 8/2019 to 1/2023 were prospectively included. A pyrophosphate bone scintigraphy (PYP) was planned to assess cardiac involvement. The prevalence of ATTR-CM and its 95% confidence interval were calculated. RESULTS: A PYP was performed in 59/82 patients. The median age was 85 [IQR 78-88] years old, 54% women. On admission, 61% had atrial fibrillation/flutter rhythm and the median NT-Pro-Bnp was 3536 [IQR 1700-7748] pg/nl. The mean ejection fraction was 57% (± 5). The prevalence of ATTR-CM diagnosed by bone scintigraphy with PYP was 19% (95%CI 9.7-30.1). No differences were found compared with those patients who did not perform a PYP. CONCLUSION: In patients admitted for heart failure with preserved ejection fraction and septal thickness, the diagnosis of ATTR-CM was relatively common (1/5). We believe that it should be routinely explored.

Introducción: La amiloidosis cardíaca por transtiretina (TTR) se suele presentar como insuficiencia cardiaca (IC) con fracción de eyección preservada. Diagnosticarla tiene impacto clínico, ya que actualmente se dispone de tratamiento específico. El objetivo de este estudio fue evaluar la prevalencia en nuestro medio de TTR en pacientes hospitalizados por IC con función sistólica preservada e hipertrofia septal. Métodos: Estudio de corte transversal. Se incluyeron de forma prospectiva pacientes mayores a 18 años internados por IC con función sistólica conservada (fracción de eyección mayor a 50%) y espesor septal mayor o igual a 12 mm durante el periodo del 8/2019 a 1/2023. El compromiso cardiaco se evaluó mediante un centellograma óseo con pirofosfato (PYP) Se calculó la prevalencia de amiloidosis por TTR y su IC95%. Resultados: Se efectuó un centellograma en 59/82 pacientes. La edad fue de 85 [RIC 78-88] años, el 54% mujeres. Al ingreso, el 61% presentó ritmo de fibrilación/aleteo auricular y una mediana de NT-Pro-Bnp de 3536 pg/ml [RIC 1700-7748 pg/nl]. La media de fracción de eyección fue de 57 (± 5) %. La prevalencia de amiloidosis cardiaca por TTR diagnosticada por centellograma óseo con PYP fue del 19% (IC95% 9,7-30,1). No se detectaron diferencias con los 23 pacientes que no efectuaron centellograma. Conclusiones: En pacientes internados por IC con fracción de eyección preservada y engrosamiento septal el diagnóstico de amiloidosis cardiaca por TTR fue relativamente frecuente (1/5), por lo que consideramos que debería explorarse en forma rutinaria.

Transthyretin amyloid cardiomyopathy in severe aortic stenosis submitted to valve replacement: a multicenter study.

Aim: To evaluate the prevalence of TTR amyloid cardiomyopathy (ATTR-CM) in severe aortic stenosis (SAS) patients, and to determine the independent predictors of major adverse events (MAE).Patients & methods: 91 SAS patients >65 years with an interventricular septum thickness ≥12.5 mm were referred for aortic valve replacement (AVR). 99mTc-DPD scintigraphy was applied to diagnose ATTR-CM, in the absence of monoclonal protein.Results: ATTR-CM was found in 11%. 78% of patients underwent AVR, but only 2 had ATTR-CM. There were no significant differences in the composite of all cause-mortality or cardiovascular hospitalizations. Lower left ventricle ejection fraction and not performing AVR were independent predictors of MAE.Conclusion: Not performing AVR was an independent predictor of MAE, regardless the ATTR-CM diagnosis.

Our study aimed to evaluate the number of people with severe narrowing of the aortic valve (SAS) and damage to the heart muscle caused to the deposition of filamentous structures composed of TTR (ATTR-CM), and to determine the independent predictors of severe undesirable medical occurrences (MAE). 91 patients >65 years with SAS and increased thickness of the heart muscle were referred to perform an aortic valve prosthesis implantation (AVR). A nuclear medicine exam was used to diagnose ATTR-CM, after excluding the deposition of filamentous structures composed of blood proteins in the heart muscle. ATTR-CM was found in 11%. 78% of patients underwent AVR, but only two had ATTR-CM. There were no significant differences in both death rate from all causes or hospitalizations from cardiovascular causes. A lower percentage of blood pumped out of the heart in each beat and not performing AVR independently predicted the occurrence of MAE in SAS patients, regardless the ATTR-CM diagnosis.

Changes of clinical characteristics, distribution of red flags and prognosis in contemporary patients with wild-type transthyretin amyloidosis cardiomyopathy.

AIM: Increased diagnostic awareness and specific disease treatments have changed the landscape of transthyretin cardiac amyloidosis (ATTR). Patients with wild-type ATTR (ATTRwt) are increasingly being diagnosed, potentially changing the clinical profile and prognosis compared with existing retrospective data. We aimed to study the clinical characteristics, distribution of red flags and prognosis of contemporary ATTRwt patients. METHODS: From January 1st 2017, to December 31st 2022, 213 consecutive patients were diagnosed with ATTRwt and prospectively followed up. Data on clinical characteristics, biomarkers, echocardiography findings, hospitalization due to worsening heart failure (WHF) and all-cause mortality were collected. RESULTS: A 37% increase in newly diagnosed patients from 2017-2019 (n = 90) vs. 2020-2022 (n = 123) was observed. The majority of patients presented with NAC disease stage I in the latter period (49% in 2017-2019 vs. 58% in 2020-2022, p = .16). Red flags were primarily cardiac-related, including elevated NT-proBNP, impaired left ventricular longitudinal systolic strain with an apical sparing pattern, heart failure with increased left ventricular wall thickness and elevated troponins. NAC disease stage I as well as low NT-proBNP levels (<1000 ng/L) were significantly associated with better survival (both p < .001). When compared with NAC disease stage II + III combined, patients with NAC disease stage I had a significantly lower risk of WHF hospitalization or death (log rank test: p = .0001). Independent predictors of the combined endpoint WHF hospitalization or death were NT-proBNP (HR 1.03 [95% CI 1.00-1.07], p < .049) and prior implantation of permanent pacemaker (HR 2.01 [1.30-3.11], p = .002). CONCLUSION: Increased diagnostic awareness resulted in a 37% increase in newly diagnosed patients in 2020-2022 vs. 2017-2019. As expected all-cause mortality but also the morbidity in terms of risk of hospitalization with WHF were significantly lower in patients with NAC disease stage I, as well as in those with low NT-proBNP levels <1000 ng/L. These findings underline the importance of continuous attention to diagnostic awareness, as early diagnosis is critical for initiating both general and specific ATTR treatment, thus improving prognosis.

99mTc-PYP and 68Ga-FAPI PET/CT Images of Hereditary Transthyretin Amyloidosis With Cardiac Involvement.

ABSTRACT: Amyloidosis is a protein misfolding disorder characterized by the extracellular deposition of insoluble amyloid fibrils, derived from abnormally folded proteins. These fibrils disrupt tissue structure and function, leading to organ dysfunction. The condition encompasses various subtypes, each associated with distinct precursor proteins and clinical manifestations. 99mTc-PYP scintigraphy is used widely and holds significant importance for diagnosis. 68Ga-FAPI is also a promising radiotracer for various diseases. To our knowledge, this is the first case of a patient with hereditary transthyretin amyloidosis with cardiac involvement, which FAPI PET showed diffuse increased myocardial uptake.

[Clinical case of generalized amyloidosis (ATTR-amyloidosis) with a progressive course of chronic heart failure. Case report].

Despite the presence of various signs of cardiac amyloidosis ("red flags"), the introduction into routine practice of new non-invasive diagnostic methods (Speckle Tracking technology using echocardiography, myocardial scintigraphy with technetium pyrophosphate, genetic testing, screening for free light chains of immunoglobulins to exclude AL-amyloidosis), which have high specificity and sensitivity, transthyretinic (ATTR) cardiomyopathy is still a difficult to diagnose disease, especially in the early stages when treatment is most effective. The article presents a clinical case of ATTR-amyloidosis with predominant heart damage, manifested by severe diastolic heart failure resistant to treatment. The timing, from the moment of the first episode of decompensation of heart failure to death, is 4 months, which confirms the rapid progression of severe biventricular dysfunction of the heart. Despite the presence of cardiac and extracardial "red flags" of ATTR-amyloidosis in the patient, the diagnosis was established at autopsy. The paper analyzes possible errors of early diagnosis at the outpatient and inpatient stages of patient management.

Cardiac amyloidosis prevalence and 1-year outcome in patients with aortic stenosis undergoing transaortic valve implantation: Findings from the CAMPOS-TAVI study.

BACKGROUND: Transthyretin amyloid cardiomyopathy (ATTR-CM) can manifest as rhythm disorders, heart failure, but also valvular degeneration. Despite aortic stenosis (AS) being prevalent among the elderly, data on ATTR-CM prevalence and outcome in patients with AS undergoing transaortic valve implantation (TAVI) remain scarce. AIM: To determine ATTR-CM prevalence and evaluate 1-year survival in patients undergoing TAVI. METHODS: Between December 2020 and September 2021, 100 consecutive patients underwent TAVI and were screened prospectively for ATTR-CM using bone scintigraphy (BS). Monoclonal gammopathy was ruled out in case of cardiac uptake on BS. All patients were followed prospectively for 1year after TAVI. RESULTS: The proportion of patients aged≥75years or with a EuroSCORE II>8% and possible femoral access was 99%. The abnormal cardiac uptake rate on BS was 7% (95% confidence interval: 2-12%); 86% of these patients were male. The RAISE (remodelling, age, injury, system and electrical) score, indicative of ATTR-CM risk, was higher in case of positive BS (P=0.04). Patients with positive BS were older and exhibited wider QRS complexes on electrocardiography (P=0.003), a higher frequency of reduced LVEF (57% vs. 17%), impaired basal LV strain (P=0.02) and a lower voltage/mass ratio (P=0.01). History of pacemaker implantation before TAVI was higher in the positive BS group (P=0.0004) and remained the only statistically significant factor after adjustment using the Holm-Bonferroni method. One-year survival of patients with positive BS did not differ from that of patients with isolated AS. CONCLUSIONS: Prevalence of ATTR-CM in patients treated with TAVI, underscoring the need for continued surveillance for potential development of ATTR-CM after TAVI. Caution is warranted regarding the 1-year survival because of the lack of study power. Further investigations are needed to define long-term prognosis of AS with ATTR-CM.

Prevalence, clinical significance and prognosis value of liver stiffness measurement anomalies in transthyretin cardiac amyloidosis.

Background - Laboratory liver anomalies are common in cardiac amyloidosis; however, their significance regarding liver stiffness is unknown. The aim of this study was to investigate the prevalence, clinical significance, and prognostic value of liver stiffness measurement (LSM) anomalies in transthyretin cardiac amyloidosis (ATTR-CA). Methods - Consecutive patients diagnosed with ATTR-CA who underwent liver stiffness assessment were included in the study. Demographic, clinical, laboratory, transthoracic echocardiography and liver stiffness data were retrospectively collected. LSM was obtained through either transient elastography or supersonic shear imaging. Patient cohort was divided in two groups according to a 10 kPa threshold. Follow up data were collected for the occurrence of hospitalization for heart failure and all-cause death. Results - Two hundred and eighty-four patients with ATTR-CA - 26 (9 %) hereditary variant ATTR, 258 (91 %) wild-type ATTR - were included. A LSM over 10 kPa was found in 4 (15 %) and 98 (38 %) patients with ATTRv and ATTRwt respectively (p = 0.02). Among patients with ATTRwt, high LSM was more frequent in advanced stages of ATTR-CA and was associated with increased risk of hospitalization for heart failure after multivariate analysis with a hazard ratio of 2.41 [1.05-5.55] (p = 0.04). Among patients with NYHA stage 1, 28 % presented high LSM associated with high NT-proBNP levels. Integration of high LSM with NT-proBNP and estimated glomerular filtration rate provided a better estimate of patient survival. Conclusion - LSM over 10 kPa is found in up to 36 % of patients with ATTR-CA and is associated with advanced stages of cardiomyopathy and increased risk of hospitalization for heart failure in ATTRwt patients.

Switching from inotersen to eplontersen in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: analysis from NEURO-TTRansform.

BACKGROUND: The phase 3 NEURO-TTRansform trial showed eplontersen treatment for 65 weeks reduced transthyretin (TTR), halted progression of neuropathy impairment, and improved quality of life (QoL) in adult patients with hereditary TTR-mediated amyloidosis with polyneuropathy (ATTRv-PN), vs. historical placebo. METHODS: NEURO-TTRansform enrolled patients with ATTRv-PN. A subset of patients were randomized to receive subcutaneous inotersen 300 mg weekly (Weeks 1-34) and subsequently switched to subcutaneous eplontersen 45 mg every 4 weeks (Weeks 37-81). Change in serum TTR and treatment-emergent adverse events (TEAEs) were evaluated through Week 85. Effects on neuropathy impairment, QoL, and nutritional status were also evaluated. RESULTS: Of 24 patients randomized to inotersen, 20 (83%) switched to eplontersen at Week 37 and four discontinued due to AEs/investigator decision. Absolute change in serum TTR was greater after switching from inotersen (-74.3%; Week 35) to eplontersen (-80.6%; Week 85). From the end of inotersen treatment, neuropathy impairment and QoL were stable (i.e., did not progress) while on eplontersen, and there was no deterioration in nutritional status. TEAEs were fewer with eplontersen (Weeks 37-85; 19/20 [95%] patients) compared with inotersen (up to Week 35; 24/24 [100%] patients). Mean platelet counts decreased during inotersen treatment (mean nadir reduction ‒40.7%) and returned to baseline during eplontersen treatment (mean nadir reduction, ‒3.2%). CONCLUSIONS: Switching from inotersen to eplontersen further reduced serum TTR, halted disease progression, stabilized QoL, restored platelet count, and improved tolerability, without deterioration in nutritional status. This supports a positive benefit-risk profile for patients with ATTRv-PN who switch from inotersen to eplontersen.

Substrate Characterization and Outcomes of Ventricular Tachycardia Ablation in Amyloid Cardiomyopathy: A Multicenter Study.

BACKGROUND: Sustained ventricular tachycardia (VT) in cardiac amyloidosis is uncommon, and the substrate and outcomes of catheter ablation are not defined. METHODS: We included 22 consecutive patients (mean age, 68±10 years; male sex, 91%) with cardiac amyloidosis (ATTR [transthyretin], n=16; light chain, n=6) undergoing catheter ablation for VT/ventricular fibrillation (VF) between 2013 and 2023 in a retrospective, observational, international study. The primary efficacy outcome was recurrent VT/VF during follow-up, while the primary safety end point included major procedure-related adverse events. RESULTS: The indication for ablation was drug-refractory VT in 17 patients (77%), and premature ventricular complex-initiated polymorphic VT/VF in 5 patients (23%). Catheter ablation was performed using endocardial (n=17.77%) or endo-epicardial approaches (n=5.23%). Complete endocardial electroanatomical voltage maps of the left and right ventricles were obtained in 17 (77%) and 10 (45%) patients, respectively. Each patient had evidence of low-voltage areas, most commonly involving the interventricular septum (n=16); late potentials were recorded in 16 patients (73%). A median of 1 (1-2) VT was inducible per patient; 12 of the 26 mappable VTs (46%) originated from the interventricular septum. Complete procedural success was achieved in 16 patients (73%), with 4 (18%) major procedure-related adverse events. After a median follow-up of 32 (14-42) months, sustained VT/VF recurrence was observed in 9 patients (41%); survival free from VT/VF recurrence was 56% (95% CI, 36%-86%) at 36-month follow-up, and most patients remained on antiarrhythmic drugs. A significant reduction in per patient implantable cardioverter defibrillator therapies was noted in the 6-month period after ablation (before: 6 [4-9] versus after: 0 [0-0]; P<0.001). In multivariable analysis, complete procedural success was associated with reduced risk of recurrent VT/VF (hazard ratio, 0.002; P=0.034). CONCLUSIONS: Catheter ablation can achieve control of recurrent VT/VF in more than half of patients with cardiac amyloidosis, and the reduction in VT/VF burden post-ablation may be relevant for quality of life. Septal substrate and risk of procedure-related complications challenge successful management of patients with cardiac amyloidosis and VT/VF.

Renal tubular acidosis in hereditary transthyretin amyloidosis (ATTRv).

INTRODUCTION: Hereditary transthyretin amyloidosis (ATTRv) is a severe autosomal dominant systemic disease. It affects the peripheral and autonomic nervous systems, heart, kidneys, and eyes. Amyloid deposition has been demonstrated in the glomerular and tubulointerstitial compartments of the kidney. Therefore, urinary acidification disorders such as renal tubular acidosis (RTA) may be early manifestations of renal involvement in this population. OBJECTIVE: To evaluate the prevalence of RTA in individuals with ATTRv. METHODS: We included symptomatic and asymptomatic individuals with TTR mutation, older than 18 years, GFR >45 mL/min/1.73m2, without systemic metabolic acidosis. Urinary acidification protocol was performed with furosemide and fludrocortisone after 12 h of water deprivation (water deprivation test - WDT) and measurements of urine ammonium ( UNH 4 + ) and titratable acidity (UTA). Proximal RTA (pRTA) was diagnosed when FEHCO3>10%. Incomplete form distal RTA (dRTA) was diagnosed if UpH>5.3. RESULTS: We selected 49 individuals with a mean age of 40 (35.5-56.5) years, 63% of which were female, 84% were Caucasian, and mean GFR was 85.5 ± 20.5 mL/min/1.73m2. 94% had the genetic variant Val50Met and 57% were symptomatic. The prevalence of pRTA was 2% and of dRTA was 16.3%. In the subgroup with dRTA, there was no significant increase in excretion of UNH 4 + and UTA. We observed a good correlation between UpH by potentiometry and UpH dipstick. A UpH<5.5 on the dipstick had 100% sensitivity and negative predictive value to exclude dRTA. CONCLUSION: A high prevalence of RTA was found in individuals with TTR mutations. The UpH dipstick after WDT had good accuracy for screening for dRTA. Further studies are needed to evaluate the impact of early diagnosis and treatment of RTA in this population.

Impact of Anemia on Mortality and Morbidity in Transthyretin Amyloid Cardiomyopathy.

Anemia is prevalent in transthyretin amyloid cardiomyopathy (ATTR-CM), but its prognostic significance remains uncertain because of conflicting data mainly in patients not receiving disease-modifying therapy. Additionally, the effect of anemia on morbidity in this population has not been studied. This retrospective study included 270 patients diagnosed with ATTR-CM, receiving disease-modifying treatment (tafamidis), of which 30% (n = 80) were anemic (defined as a hemoglobin level <13 g/100 ml for males and <12 g/100 ml for females according to the World Health Organization). At baseline, patients with anemia were on average older (mean age 79 vs 77 years), more likely to be female (21% vs 12%), and exhibited higher symptom severity based on the New York Heart Association class (42% in class III vs 27%) compared with those without anemia. Additionally, they had a worse Columbia score (mean score 3 vs 5) and Columbia stage (12% in late-stage vs 7.1%) than those without anemia. Kaplan-Meier analysis indicates that anemia was associated with a higher likelihood of mortality, all-cause, and cardiovascular (CV) hospitalizations (p <0.05). However, in the Cox regression analysis, after adjusting for baseline age, ATTR genotype, and Columbia score, anemia was only associated with a higher risk of all-cause hospitalizations (hazard ratio 1.9 (1.3 to 2.7), p <0.001) and CV-related hospitalizations (hazard ratio 1.9 (1.2 to 2.9), p = 0.006). In conclusion, this study indicates that anemic patients with ATTR-CM have higher risks of CV and all-cause hospitalizations compared with nonanemic ATTR-CM patients. Further research is needed to understand how treating anemia may improve outcomes in this high-risk patient population.

Outcomes in Cardiac Transthyretin Amyloidosis and Association With New York Heart Association Class: Real-World Data.

BACKGROUND: Results from ATTR-ACT (Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy) indicate that tafamidis prolongs survival and reduces cardiovascular hospitalizations in cardiac transthyretin amyloidosis (ATTR-CA). However, real-world data supporting these findings are scarce. Thus, we sought to characterize the clinical outcome of patients with ATTR-CA treated with tafamidis in a real-world setting and assess the prognostic role of the New York Heart Association (NYHA) classification. METHODS AND RESULTS: We conducted a retrospective observational study, enrolling a consecutive sample of patients with ATTR-CA (wild-type or variant) treated with tafamidis. Clinical outcome was tracked through follow-up visits or phone calls. Primary outcomes were death and major adverse cardiac events (MACE), a composite end point of death and hospitalizations for acute cardiac decompensation, myocardial infarction, severe arrythmias, or stroke. Kaplan-Meier analysis estimated overall and MACE-free survival including NYHA subgroups (NYHA I/II versus NYHA III). One hundred sixty-seven patients with ATTR-CA (94.6% wild-type) were enrolled and followed for a median of 539 [323-869] days. Median overall survival was not reached. Estimated 1-year, 2-year, and 5-year overall survival among the whole cohort was 93.5%, 85.9%, and 70.2%, respectively. Overall survival was higher in the NYHA I/II subgroup (P=0.002). Median MACE-free survival time was 1082 (95% CI, 962-1202) days. MACE-free survival was higher in the NYHA I/II subgroup (P<0.001). With respective hazard ratios of 5.85 (95% CI, 1.48-23.18; P=0.012) and 3.95 (95% CI, 1.99-7.84; P<0.001), NYHA III was an independent predictor of death and MACE. CONCLUSIONS: Treatment of ATTR-CA with tafamidis led to substantial improvements of clinical outcome. NYHA classification at treatment initiation is a reliable tool to provide patients with individualized prognostic information.

Palinacousis in amyloidosis: exploring the hallucinatory phenomenon in brain pathology-a case report.

BACKGROUND: Hereditary transthyretin amyloidosis, caused by transthyretin gene mutations, progresses with systemic impact and often presents peripheral neuropathy. Recent research reveals central nervous system involvement, marked by leptomeningeal amyloid accumulation and transient focal neurological episodes displaying cortical dysfunction. CASE PRESENTATION: A 47-year-old Caucasian man with hereditary transthyretin amyloidosis presented with motor aphasia, right hemiparesis, fever, and an altered state of consciousness. Tests ruled out stroke or infection. While improving, the patient reported an ongoing auditory repetition phenomenon for 48 hours despite efforts to shift focus or introduce new stimuli. CONCLUSION: This represents the first known case report documenting palinacousis in hereditary transthyretin amyloidosis attributed to central nervous system involvement. This case highlights the complexities in assessment and management of patients when neurological and psychiatric symptoms overlap.

Effectiveness of patisiran after switching from tafamidis for the treatment of hereditary transthyretin-mediated amyloidosis with polyneuropathy.

BACKGROUND AND PURPOSE: Hereditary transthyretin-mediated amyloidosis with polyneuropathy (ATTRv-PN [v for variant]) is a rare, progressive disease associated with multisystemic impairments. This study assessed the real-world outcomes of patients with ATTRv-PN who switched from tafamidis to patisiran, as well as the reasons for the treatment switch. METHODS: This was a retrospective chart review study at a large expert referral center. Data were extracted from medical charts of patients with ATTRv-PN who switched from tafamidis to patisiran on or before 30 August 2019. Data elements included demographic and clinical characteristics, rationale for switch, and disease measures evaluated from tafamidis initiation through the 12-month patisiran treatment period. RESULTS: Among the 24 patients with ATTRv-PN included in the study, 50.0% had a V30M variant, and the mean (SD) age was 67.3 (8.0) years. During tafamidis treatment (mean [SD] = 30.1 [17.5] months) before switching to patisiran, patients worsened across multiple polyneuropathy measures, including walking ability, Neuropathy Impairment Score, and autonomic function. Neuropathic disease progression on tafamidis was the principal reason for switching to patisiran. After 12 months on patisiran (mean [SD] = 11.7 [1.4] months), patients experienced attenuated disease progression or improvement in the aforementioned measures of polyneuropathy. CONCLUSIONS: Switching from tafamidis to patisiran attenuated the rate of functional decline, and most patients experienced stabilization or improvement of at least one polyneuropathy measure within 12 months of patisiran treatment. Timely switch from tafamidis to patisiran can be beneficial to avoid rapid disease progression in patients with ATTRv-PN.

Transthyretin amyloid cardiomyopathy in patients with unexplained increased left ventricular wall thickness.

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.