Phenotype and prognostic factors in geriatric and non-geriatric patients with transthyretin cardiomyopathy.

AIMS: Transthyretin cardiac amyloidosis (ATTR-CM) may be an underestimated cause of heart failure among geriatric patients and represent a unique phenotype and prognostic profile. METHODS AND RESULTS: This retrospective, observational, cohort study characterizes cardiac and extracardiac disorders at diagnosis and assesses prognosis among ATTR-CM patients based on age (geriatric vs. non-geriatric) and amyloidosis subtype (wild type, ATTRwt and hereditary, ATTRv). In total, 943 patients with ATTR-CM were included, of which 306 had ATTRv and 637 had ATTRwt. Among these, 331 (35.1%) were non-geriatric (<75 years), and 612 (64.9%) were geriatric (≥75 years). The population exhibited conduction abnormalities, atrial fibrillation and ischaemic heart disease that progressively deteriorated with age. Among ATTRwt patients, peripheral neuropathy, neurovegetative symptoms, and hearing loss were present across all age groups, but reports of carpal tunnel symptoms or surgery decreased with age. Conversely, among ATTRv patients, reports of extracardiac symptoms increased with age and Val122ILe mutation was highly prevalent among geriatric patients. The 3-year survival was higher among non-geriatric ATTR-CM patients (76%) than geriatric patients (55%) and predictors of 3-year mortality differed. Notably, predictors identified among geriatric patients were alkaline phosphatase (ALP) (HR = 1.004, 95% CI: [0.001-1.100)], troponin T hs (HR = 1.005, 95% CI: [1.001-1.120)] and tricuspid insufficiency (HR = 1.194, 95% CI: [1.02-1.230)]. Whereas, among non-geriatric patients, NT-proBNP (HR = 1.002, 95% CI: [1.02-1.04], global longitudinal strain (HR = 0.95, 95% CI: [0.922-0.989], and glomerular filtration rate (HR = 0.984, 95% CI: [0.968-1.00) were identified. We propose a 3-stage prognostic staging system combining troponin T hs (≥44 ng/L) and ALP levels (≥119 UI/L). In the geriatric population, this model discriminated survival more precisely than the National Amyloidosis Centre staging, particularly for classifying between stage 1 (82%), stage 2 (50%) and stage 3 (32%) for ATTRv and ATTRwt. CONCLUSIONS: These diagnostic and prognostic indicators, along with ATTR subtype, highlight the distinct characteristics of this important, geriatric ATTR-CM patient group. Recognizing these mortality markers can be valuable for geriatricians to improve the prognostic quality management of geriatric patients with ATTR-CM.

Changes in amyloidosis phenotype over 11 years in a cardiac amyloidosis referral centre cohort in France.

BACKGROUND: Early cardiac amyloidosis (CA) diagnosis enables patients to access effective treatments for better long-term outcomes, yet it remains under-recognised, misdiagnosed and inadequately managed. AIM: To reduce diagnostic delays, we aimed to describe the epidemiological and clinical characteristics and changes over an 11-year period. METHODS: This was a retrospective, observational cohort study of all patients referred to the Henri-Mondor Hospital for suspected CA. RESULTS: Overall, 3194 patients were identified and 3022 were included and analysed. Our patients came from varied ethnic backgrounds, and more than half (55.2%) had confirmed CA. Over 11 years, referrals increased 4.4-fold, mostly from cardiologists. Notably, wild-type transthyretin amyloidosis (ATTRwt) became the predominant diagnosis, with referrals increasing 15-fold from 20 in 2010-2012 to 308 in 2019-2020. The number of amyloid light chain (AL) diagnoses increased, whilst variant transthyretin amyloidosis (ATTRv) numbers remained relatively stable. Concerning disease severity, AL patients presented more frequently with severe cardiac involvement whereas an increasing number of ATTRwt patients presented with National Amyloid Centre stage I (22.0% in 2013-2014 to 45.9% in 2019-2020). Lastly, among patients diagnosed with ATTRv in 2019-2020, 83.9% had ATTR Val122Ile cardiac phenotype. CONCLUSIONS: This study shows that increasing cardiologist awareness and referrals have increased CA diagnoses. With improved awareness and non-invasive diagnostic techniques, more patients with ATTRwt with milder disease and more ATTRv Val122Ile mutations are being referred and diagnosed. Although more AL cases are being recognised, patients are diagnosed with severe cardiac involvement.

Amylo-AFFECT-QOL, a self-reported questionnaire to assess health-related quality of life and to determine the prognosis in cardiac amyloidosis.

Background and aims: Self-reported questionnaires are useful for estimating the health-related quality of life (HR-QoL), impact of interventions, and prognosis. To our knowledge, no HR-QoL questionnaire has been developed for cardiac amyloidosis (CA). This study aimed to validate Amylo-AFFECT-QOL questionnaire to assess HR-QoL and its prognostic value in CA. Methods: A self-reported questionnaire, "Amylo-AFFECT" had been designed and validated for CA symptoms evaluation and screening by physicians. It was adapted here to assess HR-QoL (Amylo-AFFECT-QOL) and its prognostic value in CA. To validate the theoretical model, internal consistency and convergent validity were assessed, particularly correlations between Amylo-AFFECT-QOL and the HR-QoL Minnesota Living Heart Failure (MLHF) questionnaire. Results: Amylo-AFFECT-QOL was completed by 515 patients, 425 of whom (82.5%) had CA. Wild-type and hereditary transthyretin amyloidosis (ATTRwt and ATTRv) and immunoglobulin light-chain amyloidosis (AL) were diagnosed in 47.8, 14.7, and 18.8% of cases, respectively. The best HR-QoL evaluation was obtained with five dimensions: "Heart failure," "Vascular dysautonomia," "Neuropathy," "Ear, gastrointestinal, and urinary dysautonomia," and "Skin or mucosal involvement." The global Amylo-AFFECT-QOL and MLHF scores showed significant positive correlations (rs = 0.72, p < 0.05). Patients with a final diagnosis of CA had a global Amylo-AFFECT-QOL score significantly higher than the control group composed by patients with other diagnoses (22.2 ± 13.6 vs. 16.2 ± 13.8, respectively, p-value < 0.01). According to the Amylo-AFFECT-QOL global results, ATTRv patients' QoL was more affected than AL patients' QoL or ATTRwt patients' QoL. Patients with a higher HR-QoL score had a greater risk of death or heart transplant after 1 year of follow-up (log-rank < 0.01). Conclusion: Amylo-AFFECT-QOL demonstrates good psychometric properties and is useful for quantifying HR-QoL and estimating CA prognosis. Its use may help to improve overall management of patients with CA.

Natural course and determinants of short-term kidney function decline in hereditary transthyretin amyloidosis: a French observational study.

Data regarding renal involvement in patients with hereditary transthyretin (ATTRv) amyloidosis are scarce and the natural course of chronic kidney disease (CKD) in this population remains unclear. This observational study, including adult patients diagnosed with ATTRv amyloidosis at the French Reference Centre for Cardiac Amyloidosis, investigated renal function outcome and its determinants. Multivariable logistic regression models identified factors associated with CKD at baseline. Determinants of the change in estimated glomerular filtration rate (eGFR) over 24 months of follow-up were assessed with a multivariable linear mixed-effects model. In total, 232 patients (78 women [34%], mean age: 64 years) with ATTRv amyloidosis were classified on the basis of their TTR variants: ATTRV122I (37%), ATTRV30M (29%), and other variants (34%). Median baseline eGFR was 78 ml/min/1.73 m2. Seventy-two patients (31%) had an eGFR below 60 ml/min/1.73m2 and 27/137 patients (20%) had significant proteinuria (urine protein/creatinine ratio ≥30 mg/mmol). Renal biopsy, performed in four cases, found typical Congo red-positive and TTR-labelled amyloid deposits in all cases. Older age (OR 1.07, p < .001) and a prior history of hypertension (OR 2.09, p = .04) were associated with a higher prevalence of CKD at baseline, whereas higher left ventricular global longitudinal strain (LVGLS) (OR 0.83, p < .001) was associated with a lower prevalence. The estimated change in eGFR was -7.12 [-9.61, -4.63] and -8.21 [-10.81, -5.60] ml/min/1.73 m2 after 12 and 24 months of follow-up, respectively. eGFR decline was independently associated with older age ((67-74], coefficient= -14.35 mL/min/1.73 m2, p < .01, >74, coefficient = -22.93 mL/min/1.73 m2, p < .001, versus <56), ATTRV122I (coefficient = -17.17 mL/min/1.73m2, p < .01, versus ATTRV30M) and LVGLS (coefficient = 1.22, p < .01). These data suggest that CKD is a common finding in patients with ATTRv amyloidosis, and that eGFR decline is rapid during the first year of evaluation. Older age, lower LVGLS and ATTRV122I were associated with a worse renal outcome. Further studies are now needed to evaluate effects of new targeted therapies on long term renal function.

Usefulness of Longitudinal Strain Adjusted to Regional Thickness in Hypertrophic Cardiomyopathy.

Background. We assessed the usefulness of a longitudinal strain adjusted to regional thickness in hypertrophic cardiomyopathy (HCM). Indeed, with conventional software, the width of the region of interest (ROI) is the same over the entire myocardial wall, wherein the software analyzes only partially the left ventricular (LV) hypertrophic segments. Methods. We included 110 patients: 55 patients with HCM (HCM group) and 55 healthy subjects (age- and sex-matched control group). The global longitudinal strain (GLS) and regional strain for each of the 17 segments was calculated with standard software (for two groups) and with software adjusted to the myocardial wall thickness (for the HCM group). Results. GLS was significantly decreased in the HCM group compared to the control group (−15.1 ± 4.8% versus −20.5 ± 4.3%, p < 0.0001). In the HCM group, GLS (standard method versus adjusted to thickness) measurements were not significantly different (p = 0.34). Interestingly, the regional strain adjusted to thickness was significantly lower than the standard strain in the hypertrophic segments, especially in the basal inferoseptal segment (p = 0.0002), median inferoseptal segment (p < 0.001) and median anteroseptal segment (p = 0.02). The strain adjusted to thickness was still significantly lower in the most hypertrophic segments (≥20 mm) (−3.7 ± 3%, versus −5.9 ± 4.4%, p = 0.049 in the basal inferoseptal segment and −5.7 ± 3.5% versus −8.3 ± 4.5%, p = 0.0007 in the median inferoseptal segment). In the segments with significant myocardial fibrosis, the longitudinal strain adjusted to thickness was significantly lower than the conventional strain (−8.3 ± 3.3% versus −11.4 ± 4.5%, p = 0.002). The analysis of the strain adjusted to thickness had a better feasibility (97.5% versus 99%, p = 0.01). Conclusions. The analysis of a longitudinal strain adjusted to regional thickness is feasible in HCM and allows a better evaluation of myocardial deformation, especially in the most LV hypertrophic segments.

Assessment of atrial function by myocardial deformation techniques in hypertrophic cardiomyopathy.

BACKGROUND: Diastolic dysfunction in hypertrophic cardiomyopathy (HCM) is common, but its assessment is difficult using conventional echocardiography. AIMS: To assess left atrial (LA) function in HCM by longitudinal strain and determine its role in understanding of symptoms. METHODS: We studied 144 patients divided into 3 age- and sex-matched groups: 48 consecutive patients with HCM, 48 control subjects, and 48 athlete subjects. We assessed LA function by conventional echocardiographic parameters and by longitudinal atrial strain (early-diastolic left atrial strain during reservoir phase [LASr]; end-diastolic left atrial strain during conduit phase; end-systolic peak of the left atrial strain during contraction phase). RESULTS: NYHA classification was as follows in HCM group: I in 46%, II in 31%, III in 19%, and IV in 4%. Conventional echocardiographic parameters of diastolic function were depressed in the HCM group as compared to the control and athlete groups, but not related to symptoms. All longitudinal atrial strain parameters were significantly reduced in HCM group as compared to two groups (P < .0001). LASr was significantly correlated to peak VO2 (r = 0.44, P = .01) and was the best parameter for detecting symptomatic patients presenting with HCM, with a cutoff value of 15%: Sensitivity was 71%, specificity was 79%, PPV was 77%, and NPV was 73%. CONCLUSION: Assessment of LA function in HCM is feasible using longitudinal strain, and this technique is more reliable than conventional echocardiographic parameters for the understanding of determinants of symptoms.

Impact of Coronavirus Disease 2019 outbreak on acute coronary syndrome admissions: four weeks to reverse the trend.

Data whether the COVID-19 outbreak impacts the acute coronary syndromes (ACS) admissions and the time required to reverse the downward curve are scarce. We included all consecutive patients referred for an ACS who underwent PCI from February 17, 2020 to April 26, 2020 in a high-volume PCI coronary care unit. We compared the number of ACS patients in 2020 to the same period in 2018 and 2019. Predictors of adverse outcome in ST-elevation myocardial infarction (STEMI) patients were recorded: symptom-onset-to-first medical contact (FMC), and FMC-to-sheath insertion times. During the studied period (calendar weeks 8-17, 2018-2020), 144 ACS patients were included. In 2020, we observed two distinct phases in the ACS admissions: a first significant fall, with a relative reduction of 73%, from the week of lockdown (week 12) to 3 weeks later and then an increase of ACS. Median symptom-onset-to-FMC time was significantly higher in 2020 than in the two previous years (600 min [298-632] versus 121 min [55-291], p < 0.001). Median FMC-to-sheath insertion did not differ significantly (93 min [81-131] in 2020 versus 90 min [67-137] in 2018-2019, p = 0.57). The main findings are (1) a pattern of a U-curve in ACS admissions, with a first decrease in ACS admissions and a return to "normality" 4 weeks after; (2) a significant increase in the total ischemic time exclusively due to an increase in the symptom-onset-to-first-medical-contact time.