A 15-year consolidated overview of data in over 6000 patients from the Transthyretin Amyloidosis Outcomes Survey (THAOS)

Background Transthyretin amyloidosis (ATTR amyloidosis) is a progressive, multisystemic, life-threatening disease resulting from the deposition of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in various tissues and organs.Methods Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal, observational study of patients with ATTR amyloidosis, including both hereditary and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This analysis describes the baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2022), providing a consolidated overview of 15-year data from the THAOS registry.Results This analysis included 4428 symptomatic patients and 1707 asymptomatic gene carriers. The majority of symptomatic patients were male (70.8%) with a mean (standard deviation [SD]) age at symptom onset of 56.6 (17.9) years. Compared with the 14-year analysis, V30M remained the most prevalent genotype in Europe (62.2%), South America (78.6%), and Japan (74.2%) and ATTRwt remained most common in North America (56.2%). Relative to the 14-year analysis, there was an increase of mixed phenotype (from 16.6 to 24.5%) and a reduction of predominantly cardiac phenotype (from 40.7 to 31.9%). The proportion of patients with predominantly neurologic phenotype remained stable (from 40.1 to 38.7%). Asymptomatic gene carriers were 58.5% female with a mean age at enrollment of 41.9 years (SD 15.5).Conclusions This overview of > 6000 patients enrolled over 15 years in THAOS represents the largest registry analysis of ATTR amyloidosis to date and continues to emphasize the genotypic and phenotypic heterogeneity of the disease. Nearly a quarter of the symptomatic population within THAOS was mixed phenotype, underscoring the need for multidisciplinary management of ATTR amyloidosis.Trial registrationClinicalTrials.gov Identifier: NCT00628745

A 15-year consolidated overview of data in over 6000 patients from the Transthyretin Amyloidosis Outcomes Survey (THAOS)

Background Transthyretin amyloidosis (ATTR amyloidosis) is a progressive, multisystemic, life-threatening disease resulting from the deposition of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in various tissues and organs. Methods Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal, observational study of patients with ATTR amyloidosis, including both hereditary and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This analysis describes the baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2022), providing a consolidated overview of 15-year data from the THAOS registry. Results This analysis included 4428 symptomatic patients and 1707 asymptomatic gene carriers. The majority of symptomatic patients were male (70.8%) with a mean (standard deviation [SD]) age at symptom onset of 56.6 (17.9) years. Compared with the 14-year analysis, V30M remained the most prevalent genotype in Europe (62.2%), South America (78.6%), and Japan (74.2%) and ATTRwt remained most common in North America (56.2%). Relative to the 14-year analysis, there was an increase of mixed phenotype (from 16.6 to 24.5%) and a reduction of predominantly cardiac phenotype (from 40.7 to 31.9%). The proportion of patients with predominantly neurologic phenotype remained stable (from 40.1 to 38.7%). Asymptomatic gene carriers were 58.5% female with a mean age at enrollment of 41.9 years (SD 15.5). Conclusions This overview of > 6000 patients enrolled over 15 years in THAOS represents the largest registry analysis of ATTR amyloidosis to date and continues to emphasize the genotypic and phenotypic heterogeneity of the disease. Nearly a quarter of the symptomatic population within THAOS was mixed phenotype, underscoring the need for multidisciplinary management of ATTR amyloidosis. Trial registration ClinicalTrials.gov Identifier: NCT00628745

Tip of the iceberg: a tertiary care centre retrospective study of left ventricular hypertrophy aetiologies

Aims To phenotype patients referred to a tertiary centre for the exploration of a left ventricular hypertrophy (LVH) starting from 12 mm of left ventricular wall thickness (LVWT).Methods and results Consecutive patients referred for aetiological workup of LVH, beginning at 12 mm of LVWT were retrospectively included in this tertiary single-centred observational study. Patients presenting with severe aortic stenosis were excluded. Aetiological workup was reviewed for each subject and aetiologies were adjudicated by expert consensus.Among 591 patients referred for LVH aetiological workup, 41% had a maximal LVWT below 15 mm. LVH aetiologies were led by cardiac amyloidosis (CA, 34.3%), followed by sarcomeric hypertrophic cardiomyopathy (S-HCM, 32.1%), hypertensive cardiomyopathy (21.7%), unknown aetiology (7.6%) and other (4.2%), including Anderson-Fabry’s disease (1.7%). CA and S-HCM affected over 50% of patients with mild LVH (12–14 mm); the prevalence of these aetiologies rose with LVH severity. Among patients with Anderson-Fabry’s disease, 4 (40%) had a maximal LVWT <15 mm.Conclusions Mild LVH (ie, 12–14 mm) conceals multiple aetiologies that can lead to specific treatment, cascade family screening and specific follow-up. Overall, CA is nowadays the leading cause of LVH in tertiary centers

Diagnostic score for the detection of cardiac amyloidosis in patients with left ventricular hypertrophy and impact on prognosis

International audienc

Diagnostic score for the detection of cardiac amyloidosis in patients with left ventricular hypertrophy and impact on prognosis

International audienc

Successful Reversal of Severe Tachycardia-Induced Cardiomyopathy with Cardiogenic Shock by Urgent Rhythm or Rate Control: Only Rhythm and Rate Matter

Background and objectives Severe forms of Tachycardia-induced cardiomyopathy (TIC) with cardiogenic shock are not well described so far, and efficiency of catheter ablation in this setting is unknown. Methods We retrospectively included consecutive patients admitted to the Intensive Cardiac Care Unit for acute heart failure with cardiogenic shock associated with atrial arrhythmia and managed by ablation. Result Fourteen patients were included, each with cardiogenic shock and two needing the use of extracorporeal membrane oxygenation. Successful ablation was performed in the acute setting or over the following weeks. Two patients experienced relapses of arrhythmias and were treated by new ablation procedures. At 7.5 ± 5 months follow-up, all patient were alive with stable sinus rhythm. The left ventricular Ejection Fraction dramatically improved (21 vs. 54%, p = 0.001) as well as the end-diastolic left ventricular diameter (61 vs. 51 mm, p = 0.01) and NYHA class (class IV in all vs. median 1, p = 0.002). Conclusion Restoration and maintenance of sinus rhythm in severe TIC with cardiogenic shock and atrial arrhythmias lead to a major increase or normalization of LVEF, reduction of ventricular dimensions, and improvement in functional status. Ablation is efficient in long-term maintenance of sinus rhythm and may be proposed early in refractory cases

Relationships between left ventricular mass and QRS duration in diverse types of left ventricular hypertrophy

International audienceAims: Hypertrophic cardiomyopathy (HCM) may be associated with very narrow QRS, while left ventricular hypertrophy (LVH) may increase QRS duration. We investigated the relationships between QRS duration and LV mass (LVM) in subtypes of abnormal LV wall thickness.Methods and results: Automated measurement of LVM on MRI was correlated to automated measurement of QRS duration on ECG in HCM, left ventricular non compaction (LVNC), left ventricular hypertrophy (LVH), and controls with healthy hearts. Uni and multivariate analyses were performed between groups including explanatory variables expected to influence LVM and QRS duration. The relationships between QRS duration and LVM were further studied within each group. Two hundred and twenty-one HCM, 28 LVNC, 16 LVH, and 40 controls were retrospectively included. Mean QRS duration was 92 ms for HCM, 104 for LVNC, 110 for LVH, and 92 for controls (P < 0.01). Mean LVM was 100, 90, 108, and 68 g/m2 (P < 0.01). QRS duration, LVM, hypertension, maximal wall thickness, and late gadolinium enhancement were significantly linked to HCM in multivariate analysis (w/wo bundle branch block). An independent negative correlation was found between LVM and QRS duration in the HCM group, while the relationship was reverse in LVNC, LVH, and controls.Conclusion: QRS duration increases with LVM in LVNC, LVH, or in healthy hearts, while reverse relationship is present in HCM. These relationships were independent from other parameters. These results warrant additional investigations for refining diagnosis criteria for HCM in the future

Relationships between left ventricular mass and QRS duration in diverse types of left ventricular hypertrophy

International audienceAims: Hypertrophic cardiomyopathy (HCM) may be associated with very narrow QRS, while left ventricular hypertrophy (LVH) may increase QRS duration. We investigated the relationships between QRS duration and LV mass (LVM) in subtypes of abnormal LV wall thickness.Methods and results: Automated measurement of LVM on MRI was correlated to automated measurement of QRS duration on ECG in HCM, left ventricular non compaction (LVNC), left ventricular hypertrophy (LVH), and controls with healthy hearts. Uni and multivariate analyses were performed between groups including explanatory variables expected to influence LVM and QRS duration. The relationships between QRS duration and LVM were further studied within each group. Two hundred and twenty-one HCM, 28 LVNC, 16 LVH, and 40 controls were retrospectively included. Mean QRS duration was 92 ms for HCM, 104 for LVNC, 110 for LVH, and 92 for controls (P < 0.01). Mean LVM was 100, 90, 108, and 68 g/m2 (P < 0.01). QRS duration, LVM, hypertension, maximal wall thickness, and late gadolinium enhancement were significantly linked to HCM in multivariate analysis (w/wo bundle branch block). An independent negative correlation was found between LVM and QRS duration in the HCM group, while the relationship was reverse in LVNC, LVH, and controls.Conclusion: QRS duration increases with LVM in LVNC, LVH, or in healthy hearts, while reverse relationship is present in HCM. These relationships were independent from other parameters. These results warrant additional investigations for refining diagnosis criteria for HCM in the future

Patients with transthyretin amyloidosis enrolled in THAOS between 2018 and 2021 continue to experience substantial diagnostic delay

The THAOS registry and this analysis were sponsored by Pfizer. We thank all THAOS patients and investigators for their important contributions to this study. We also thank Pritam Gupta for statistical support on the manuscript. Medical writing support was provided by Emily Balevich, PhD, of Engage Scientific Solutions and was funded by Pfizer.S