Phase analysis for ventricular arrhythmia prediction: A retrospective monocentric cohort study.

BACKGROUND: Prediction of ventricular arrhythmias (VA) mostly relies on left ventricular ejection fraction (LVEF), but with limited performance. New echocardiographic parameters such as mechanical dispersion have emerged, but acoustic window sometimes precludes this measurement. Nuclear imaging may be an alternative. We aimed to assess the ability of mechanical dispersion, measured with phase standard deviation (PSD) on radionuclide angiocardiography (RNA), to predict VAs. METHODS: This retrospective monocentric observational study included all patients who underwent a tomographic RNA from 2015 to 2019. Phase analysis yielded PSD and follow-up was examined to identify VAs, heart transplantation, and death. RESULTS: The study population consisted of 937 patients, mainly with LVEF ≤ 35% (425, 45%). Most had ischemic (334, 36%) or dilated cardiomyopathies (245, 26%). We identified 86 (9%) VAs. PSD was strongly associated with the occurrence of VA [hazard ratio per 10 ms increase (HR10) 1.12 (1.09-1.16)], heart transplantation [HR10 1.09 (1.06-1.12)], and death [HR10 1.03 (1.00-1.05)]. The association between PSD and VA persisted after adjustment for age, sex, QRS duration, LVEF, global longitudinal strain (GLS), and echocardiography-assessed mechanical dispersion. CONCLUSION: The occurrence of ventricular arrhythmias was predicted by mechanical dispersion assessed by RNA, even after adjustment for LVEF and GLS.

Quantitative assessment of tricuspid regurgitation using right and left ventricular stroke volumes obtained from tomographic equilibrium radionuclide ventriculography.

BACKGROUND: Quantitative assessment of valve regurgitation using volumetric method by comparing right and left ventricular stroke volumes is still under investigations. AIMS: To investigate the accuracy of tomographic equilibrium radionuclide ventriculography (t-ERV) for the quantification of tricuspid regurgitation (TR). METHODS AND RESULTS: Sixty-one patients (44 men; mean age 59 ± 12 years) who underwent both t-ERV and transthoracic echocardiography (TTE) studies within 2 weeks for right ventricular systolic function assessment were eligible for inclusion. A sub-group of 22 patients underwent both t-ERV and CMR. Patients with mitral/aortic regurgitation by TTE were excluded of the study. TR regurgitant volume (RVol) was calculated using the proximal isovelocity surface area (PISA) method from TTE and the volumetric method (right ventricular stroke volume minus left ventricular stroke volume) from t-ERV. There was a significant correlation between RVol as assess by ERV and by TTE (R = 0.95, P < 0.0001). Intraclass correlation coefficient between TTE and ERV for TR quantification was 0.95 (P < 0.0001). Among patients who underwent CMR, the correlation between RVol obtained by TTE and by t-ERV and CMR were R = 0.81 and R = 0.75, respectively (all P < 0.0001). CONCLUSION: TR assessment using the t-ERV correlates well with PISA from TTE in patients referred for right ventricular systolic function assessment.

Value of Longitudinal Strain to Identify Wild-Type Transthyretin Amyloidosis in Patients With Aortic Stenosis.

BACKGROUND: Wild-type transthyretin-related amyloidosis (ATTRwt) and degenerative aortic stenosis (AS) are both age-related. Diagnosis of cardiac amyloidosis (CA) among patients with AS may be difficult due to overlapping morphological and functional criteria. The aim of this study was to describe an echocardiographic longitudinal strain (LS) pattern among patients with AS with and without ATTRwt.Methods and Results:Patients who have AS with ATTRwt (n=30), AS without ATTRwt (n=50) and ATTRwt without AS (n=31) underwent two-dimensional speckle-tracking echocardiography. Transthyretin CA was based on positive bone scintigraphy without monoclonal gammopathy. All patients showed a gradual decrease in LS from the base to the apex resulting in a decrease of the global LS. A cut-off value of 1.0 for relative apical LS (average apical LS/[average basal LS+mid-LS]) was sensitive (88%) but less specific (68%) in differentiating ATTRwt among patients with severe AS. The best cut-off value for relative apical LS for identifying patients with ATTRwt among the whole population was 0.9 (sensitivity 74%, specificity 66%); however, 35%, 25% and 11% of patients who have ATTRwt without AS, with moderate AS and with severe AS, respectively, did not reach this threshold. CONCLUSIONS: A decrease of global and relative apical LS is common in patients with AS, even in the absence of ATTRwt. ATTRwt CA can be present even in the absence of relative apical sparing of LS.

Severe mitral regurgitation recurrence after successful percutaneous mitral edge-to-edge repair by Mitraclip in primary mitral regurgitation: Insights from a three-dimensional echocardiography study.

BACKGROUND: The sustainability of the results of Mitraclip procedures is a source of concern. AIMS: To investigate risk factors of severe mitral regurgitation (MR) recurrence after Mitraclip in primary MR. METHODS AND RESULTS: Eighty-three patients undergoing successful Mitraclip procedures were retrospectively included. Valve anatomy and Mitraclips placement were comprehensively analyzed by post-processing 3D echocardiographic acquisition. The primary composite endpoint was the recurrence of severe MR. The average age was 83±7 years-old, 37 (44%) were female. Median follow-up was 381 days (IQR 195-717) and 17 (20%) patients reached the primary endpoint. Main causes of recurrence of severe MR were relapse of a prolapse (64%) and single leaflet detachment (23%). Posterior coaptation line length (HR 1.06 95%CI 1.01-1.12 p = 0.02), poor imaging quality (HR 3.84, 95%CI 1.12-13.19; p = 0.03), and inter-clip distance (HR 1.60, 95%CI 1.27-2.02; p < 0.01) were associated with the occurrence of the primary endpoint. CONCLUSIONS: Recurrence of severe MR after a MitraClip procedure for primary MR results from a complex interplay between anatomical (tissue excess) and procedural criteria (quality of ultrasound guidance and MitraClips spacing).

Participating in Sports After Mitral Valve Repair for Primary Mitral Regurgitation: A Retrospective Cohort Study.

OBJECTIVE: Participating in either competitive or leisure sports is restrictive after surgical mitral valve repair (MVR). In this study, we examine the impact of sports on outcomes after MVR. DESIGN: Retrospective cohort study. SETTING: Patients aged 18 to 65 years who underwent a first-time MVR for primary mitral regurgitation (MR) in a tertiary care center. PATIENTS: One hundred twenty-one consecutive patients were included in the study. The exclusion criteria were as follows: other concomitant procedures, early perioperative death or repeat intervention, noncardiac death or endocarditis during follow-up, and general contraindications for normal physical activity. ASSESSMENT OF RISK FACTORS: Participation in sports was quantified by the number of hours per week during the past 6 months, classified according to the Mitchell classification and assessed with the International Physical Activity Questionnaire (IPAQ) short form. MAIN OUTCOME MEASURES: The primary composite endpoint was MVR failure defined as MR grade ≥2 or mean transmitral gradient ≥8 mm Hg, signs and symptoms of heart failure, or late-onset postoperative AF (>3 months). RESULTS: The mean age was 50 ± 11 years, and there were 85 (71%) men. The median follow-up was 34 months [interquartile range (IQR): 20-50]. Fifty-six (46%) patients participated in sports regularly (median of 3 h/wk; IQR: 2-5). Twenty (17%) patients reached the primary composite endpoint with no correlation with participation in sports (P = 0.537), IPAQ categories (P = 0.849), in any of the Mitchell classification subgroups and a high level of participation in sports ≥6 hours (P = 0.679). CONCLUSIONS: Sports seem to be unrelated to the worst outcome after MVR.

Cardiac impact of arteriovenous fistulas: what tools to assess?

The relationship between arteriovenous access flow (Qa) and cardiovascular changes is complex. Several studies have shown cardiac remodeling and symptoms of heart failure for high-flow arteriovenous fistulas (AVF). To evaluate the early cardiovascular impact of AVF. Forty-seven patients with an AVF, hospitalized for the evaluation of high-flow AVF or a pre-kidney transplant assessment were included. We collected clinical and biological data. We also collected data of the assessment by transthoracic echocardiography, functional evaluation by 6-min-walk test and peak oxygen consumption, and measurement of coronary flow reserve by dynamic myocardial perfusion imaging. The measurement of Qa was performed by color Doppler ultrasound and then indexed to the body surface area (Qai) and to the cardiac output (CO) (Qa/CO). Patients were poorly symptomatic (18 and 1 patients NYHA stage 2 and 3, respectively). There was no correlation between Qa, Qai, or Qa/CO and functional status, assessed by peak oxygen consumption (P = 0.891; P = 0.803; P = 0.939, respectively). Symptomatic patients did not have higher Qa, Qai or Qa/CO than asymptomatic (2260 vs 2197 mL/min, P = 0.402; 1257 vs 1256 mL/min/m2, P = 0.835; and 34% vs 37%, P = 0.701, respectively). There was no correlation between Qa, Qai or Qa/CO and left ventricular end-diastolic volume or left ventricular ejection fraction. There was no correlation between coronary flow reserve and these 3 parameters of vascular access flow. However, the global longitudinal strain (GLS) was correlated with Qa and Qa/CO (R = 0.331, P = 0.023 and R = 0.380, P = 0.008, respectively). Increase of Qa or Qa/CO was associated with an alteration of the GLS. A cut-off value of 2250 mL/min for Qa allowed 83% sensitivity and 63% specificity for detecting an alteration of the GLS > - 18%. A cut-off value of 33% for Qa/CO allowed 92% sensitivity and 65% specificity. Impact of AVF on cardiac parameters is weak. However, GLS is the first parameter to be impacted by the flow of the fistula. Systematic transthoracic echocardiography evaluation with measurement of GLS should be proposed for all patients with Qa > 2250 mL/min or Qa/CO > 33%, to detect those at higher risk of cardiac impact of the AVF.

What is the most useful imaging parameter to explore the prognostic value of the right ventricular function at the time of multimodality cardiovascular imaging?

BACKGROUND: Right ventricular (RV) function is a powerful independent predictor of adverse heart failure outcomes. The aim of this study was to compare the predictive value of main RV systolic imaging parameters for outcome. METHODS: Seventy-nine patients underwent comprehensive cardiovascular imaging modalities including transthoracic echocardiography, cardiac magnetic resonance (CMR) imaging, and tomographic equilibrium radionuclide ventriculography (ERV) for the assessment of RV function. The composite primary endpoint (CPE) was defined by the occurrence of death, heart transplantation, implantation of a left ventricular assist device, or new-onset acute heart failure. RESULTS: During a mean follow-up of 13 ± 9 months, 15 (19%) patients reached the CPE. The areas under the receiver operator characteristic curves for the prediction of the CPE were 0.922 (P < .001), 0.913 (P < .001), 0.906 (P < .001), 0.849 (P = .002), 0.837 (P = .003), 0.799 (P = .009), 0.792 (P = .011), 0.753 (P = .026), 0.720 (P = .053), and 0.608 (P = .346) for integral systolic S' wave tricuspid annular velocity, RV free wall longitudinal strain (RVFWLS), RV fractional area change, tricuspid annular plane systolic excursion, RV ejection fraction (RVEF) by CMR using the 4-chamber slices, peak systolic S' wave tricuspid annular velocity, RVEF by CMR using short-axis slices, RVEF by ERV, RV myocardial performance index, and RV myocardial acceleration during isovolumic contraction, respectively. CONCLUSION: Echocardiographic parameters, and particularly integral systolic S' wave tricuspid annular velocity and RVFWLS, have the best prognostic performance.

Impact of right ventricular systolic function after heart transplantation on exercise capacity.

BACKGROUND: Right ventricular (RV) systolic parameters are difficult to assess in heart transplant recipients (HTRs) compared to healthy people because of discordant data, and their impact on exercise capacity remains undefined. We sought to retrospectively assess the impact of RV systolic function on exercise capacity after heart transplantation. METHODS: We analyzed data from 61 HTRs who underwent transthoracic echocardiography (TTE), cardiac magnetic resonance imaging (CMR), and exercise capacity assessment by 6-minute walking test (6MWT) and cardiopulmonary exercise testing (CPET) at 1- and 2-year follow-ups. RESULTS: Transthoracic echocardiography RV longitudinal systolic function including tricuspid annular plan systolic excursion (TAPSE), peak systolic S' wave tricuspid annular velocity (PSVtdi) and RV free wall longitudinal strain was decreased at 1 year (respectively, 15 ± 3 mm, 10 ± 3 cm/s, and -19 ± 5%) and at 2 years (respectively, 15 ± 3 mm, 10 ± 2 cm/s, and -20 ± 5%) with no significant difference between both evaluations; meanwhile, RV ejection fraction (RVEF) measured by CMR was preserved. Mean percentage of predicted peak oxygen consumption was altered, but improved between the first and second year (55 ± 18 vs 60 ± 18%, P = .038). PSVtdi was weakly correlated with 6MWT distance (r = .426, P = .017) and RVEF with the predicted distance at 6MWT (r = .410, P = .027) at the 1-year follow-up. CONCLUSIONS: Despite decreasing values, RV longitudinal systolic function has a weak impact on exercise capacity of HTRs. PSVtdi and RVEF are the most pertinent parameters to assess the impact of RV systolic function on exercise capacity after heart transplantation. These results should lead to redefine normal RV systolic function thresholds for HTRs.

Towards etiological treatments in cardiomyopathies.

This review proposes to look at the evolution of cardiomyopathy treatments in the light of advances in diagnostic techniques, which have enabled to move from a mechanistic to a phenotypic and then etiological approach. The article goes beyond the ejection fraction approach, and look at new therapies that target the pathophysiological pathways of cardiomyopathies, either by targeting the phenotype, or by targeting the etiology. The evolution of HCM treatments is detailed, culminating in the latest etiological treatments such as mavacamten in sarcomeric HCM, tafamidis in transthyretin cardiac amyloidosis and migalastat in Fabry disease. Myosin stimulators are reviewed in the treatment of DCM, before opening perspectives for gene therapy, which proposes direct treatment of the culprit mutation.

Descriptive study of the clinical and myocardial status of a population with anatomopathological aortic valve amyloidosis.

BACKGROUND: Aortic stenosis (AS) and transthyretin (ATTR) cardiac amyloidosis (CA) share the same clinical profiles and cardiac phenotype. Amyloid deposits have been frequently reported in aortic valves of patients with severe AS referred for surgical aortic valve replacement (SAVR). The aim of this study was to determine the clinical and myocardial status of patients with aortic valve amyloidosis after aortic valve surgery. METHODS AND RESULTS: We performed a retrospective descriptive study of 46 patients who underwent SAVR for severe AS with amyloid deposits upon histological analysis. All patients were screened for cardiac involvement. Amyloid deposits typing was successful in 35 (76%) patients and 28 (80%) were ATTR. Two (4%) had positive bone scintigraphy and among the 5 myocardial biopsies performed during surgery, 80% were positive for ATTR deposits. CONCLUSION: ATTR is the predominant type in the presence of amyloid deposits on the aortic valve after surgery for severe AS but is only rarely accompanied by cardiac uptake on bone scintigraphy. Early stages of myocardial involvement are frequent and myocardial biopsy is more sensitive for detection of mild amyloid deposits than bone scintigraphy.

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.

International prevalence of transthyretin amyloid cardiomyopathy in high-risk patients with heart failure and preserved or mildly reduced ejection fraction.

BACKGROUND: Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed cause of heart failure (HF). METHODS: This epidemiology study assessed the international prevalence of ATTR-CM among patients aged ≥60 years with a history of HF, left ventricular ejection fraction (LVEF) >40%, an end-diastolic interventricular septum thickness (IVST) ≥12 mm, but without diagnosed amyloidosis, history of LVEF ≤40%, cardiomyopathy of known cause, severe valvular, or coronary heart disease. ATTR-CM was determined using cardiac scintigraphy alongside exclusionary testing for light chain amyloidosis. The study was terminated early due to slow recruitment, without safety concerns. RESULTS: Overall, 56/315 (18%; 95% CI: 13.7-22.5) patients with evaluable scintigraphy had ATTR-CM, with a numerically higher prevalence in: Europe (24%) vs. other regions (9% Asia; 5% North America); at specialist vs non-specialist centres (26% vs. 11%); in males vs. females (24% vs. 10%); and in older vs. younger patients (e.g. >40% among those ≥85 years). Other risk markers (p<.05) included a history of carpal tunnel syndrome, higher N-terminal pro B-type natriuretic peptide concentration, and higher end-diastolic IVST. CONCLUSIONS: ATTR-CM was diagnosed in 18% (95% CI: 13.7-22.5) of evaluable patients with HF, LVEF >40%, and risk markers for ATTR-CM, but no previous diagnosis of amyloidosis. Recruitment bias may have contributed to regional variability. NCT04424914.

Catheter ablation of atrial arrhythmias in cardiac amyloidosis: Impact on heart failure and mortality.

BACKGROUND: Atrial arrhythmias (AA) commonly affect patients with cardiac amyloidosis (CA) and are a contributing risk factor for the development of heart failure (HF). This study sought to investigate the long-term efficacy and impact of catheter ablation on HF progression in patients with CA and AA. METHODS: Thirty-one patients with CA and AA undergoing catheter ablation were retrospectively included (transthyretin-ATTR CA 61% and light chain-AL CA 39%). AA subtypes included atrial fibrillation (AFib) in 22 (paroxysmal in 10 and persistent in 12), atrial flutter (AFl) in 17 and atrial tachycardia (AT) in 11 patients. Long-term AA recurrence rates were evaluated along with the impact of sinus rhythm (SR) maintenance on HF and mortality. RESULTS: AA recurrence was observed in 14 patients (45%) at a median of 3.5 months (AFib n = 8, AT n = 6, AFl = 0). Post-cardioversion, medical therapy or catheter ablation, 10 patients (32%) remained in permanent AA. Over a median follow-up of 19 months, all-cause mortality was 39% (n = 12): 3 with end-stage HF, 5 due to late complications of CA, 1 sudden cardiac death, 1 stroke, 1 COVID 19 (and one unknown). With maintenance of SR following catheter ablation, significant reductions in serum creatinine and natriuretic peptide levels were observed with improvements in NYHA class. Two patients required hospitalization for HF in the SR maintenance cohort compared to 5 patients in the AA recurrence cohort (p = 0.1). All 3 patients with deaths secondary to HF had AA recurrence compared to 11 out of the 28 patients whom were long-term survivors or deaths not related to HF (p = 0.04). All-cause mortality was not associated with AA recurrence. CONCLUSION: This study demonstrates moderate long-term efficacy of SR maintenance with catheter ablation for AA in patients with CA. Improvements in clinical and biological status with positive trends in HF mortality are observed if SR can be maintained.

Predictors and Risk Score for Immune Checkpoint-Inhibitor-Associated Myocarditis Severity.

Background: Immune-checkpoint inhibitors (ICI) are associated with life-threatening myocarditis but milder presentations are increasingly recognized. The same autoimmune process that causes ICI-myocarditis can manifest concurrent generalized myositis, myasthenia-like syndrome, and respiratory muscle failure. Prognostic factors for this "cardiomyotoxicity" are lacking. Methods: A multicenter registry collected data retrospectively from 17 countries between 2014-2023. A multivariable cox regression model (hazard-ratio(HR), [95%confidence-interval]) was used to determine risk factors for the primary composite outcome: severe arrhythmia, heart failure, respiratory muscle failure, and/or cardiomyotoxicity-related death. Covariates included demographics, comorbidities, cardio-muscular symptoms, diagnostics, and treatments. Time-dependent covariates were used and missing data were imputed. A point-based prognostic risk score was derived and externally validated. Results: In 748 patients (67% male, age 23-94), 30-days incidence of the primary composite outcome, cardiomyotoxic death, and overall death were 33%, 13%, and 17% respectively. By multivariable analysis, the primary composite outcome was associated with active thymoma (HR=3.60[1.93-6.72]), presence of cardio-muscular symptoms (HR=2.60 [1.58-4.28]), low QRS-voltage on presenting electrocardiogram (HR for ≤0.5mV versus >1mV=2.08[1.31-3.30]), left ventricular ejection fraction (LVEF) <50% (HR=1.78[1.22-2.60]), and incremental troponin elevation (HR=1.86 [1.44-2.39], 2.99[1.91-4.65], 4.80[2.54-9.08], for 20, 200 and 2000-fold above upper reference limit, respectively). A prognostic risk score developed using these parameters showed good performance; 30-days primary outcome incidence increased gradually from 3.9%(risk-score=0) to 81.3%(risk-score≥4). This risk-score was externally validated in two independent French and US cohorts. This risk score was used prospectively in the external French cohort to identify low risk patients who were managed with no immunosuppression resulting in no cardio-myotoxic events. Conclusions: ICI-myocarditis can manifest with high morbidity and mortality. Myocarditis severity is associated with magnitude of troponin, thymoma, low-QRS voltage, depressed LVEF, and cardio-muscular symptoms. A risk-score incorporating these features performed well. Trial registration number: NCT04294771 and NCT05454527.

Development and validation of machine learning algorithms to predict posthypertensive origin in left ventricular hypertrophy.

BACKGROUND: Left ventricular hypertrophy is often associated with hypertension, which is not necessarily the cause of hypertrophy. Non-hypertension-related aetiologies often have a strong impact on patient management, and therefore require a thorough and careful workup. When considering all left ventricular hypertrophies, even the mild ones, the number of patients who need a workup increases drastically. This raises the need for a tool to evaluate the pretest probability of the origin of left ventricular hypertrophy. AIM: To predict the hypertensive origin of left ventricular hypertrophy using machine learning on first-line clinical, laboratory and echocardiographic variables. METHODS: We used a retrospective single-centre population of 591 patients with left ventricular hypertrophy, starting at 12mm maximal left ventricular wall thickness. After splitting data in a training and testing set, we trained three different algorithms: decision tree; random forest; and support vector machine. Model performances were validated on the testing set. RESULTS: All models exhibited good areas under receiver operating characteristic curves: 0.82 (95% confidence interval: 0.77-0.88) for the decision tree; 0.90 (95% confidence interval 0.85-0.94) for the random forest; and 0.90 (95% confidence interval: 0.85-0.94) for the support vector machine. After threshold selection, the last model had the best balance between its specificity of 0.96 (95% confidence interval: 0.91-0.99) and its sensitivity of 0.31 (95% confidence interval: 0.17-0.44). All algorithms relied on similar most influential predictor variables. Online calculators were developed and made publicly available. CONCLUSIONS: Machine learning models were able to determine the hypertensive origin of left ventricular hypertrophy with good performances. Implementation in clinical practice could reduce the number of aetiological workups needed in patients presenting with left ventricular hypertrophy.

Frailty in Older Patients with Transthyretin Cardiac Amyloidosis.

Background-Transthyretin cardiac amyloidosis (ATTR-CA) prevalence increases with age. The interplay between frailty and heart failure has been increasingly recognized. The objective of this study is to compare clinical, biological, and transthoracic echocardiography (TTE) characteristics of older ATTR-CA patients according to the G8 frailty screening tool. Methods-Patients over 75 years old with a confirmed diagnosis of ATTR-CA were included between January 2020 and April 2021. All patients underwent a routine blood test, TTE, and a functional assessment with a six-minute walking distance test (6MWD) or cardiopulmonary exercise testing (CPET), and the G8 score was calculated. Results-Fifty-two patients were included. Thirty-nine (75%) patients were frail and their mean NYHA stage was more severe (2.2 vs. 1.7; p = 0.004); 62% of them had a Gilmore stage of 2 or 3 (p = 0.05). Global left ventricular strain (GLS) was lower (-11.7% vs. -14.9%; p = 0.014) and the interventricular septum was thicker (18 ± 2 mm vs. 17 ± 2 mm; p = 0.033) in frail patients. There were no significant differences according to functional tests. Conclusion-The majority of older patients with ATTR-CA are frail according to the G8 score. They are more symptomatic and have an increased cardiac involvement and a poorer prognosis, requiring more personalized cardiac management.

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.

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

AIMS: 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.

Impact of tricuspid regurgitation on survival in patients with cardiac amyloidosis.

AIMS: Tricuspid regurgitation (TR) is a common finding and has been associated with poorer outcome in patients with heart failure. This study sought to investigate the prognostic value of TR in patients with cardiac amyloidosis (CA). METHODS AND RESULTS: Two-hundred and eighty-three patients with CA-172 (61%) wild-type transthyretin amyloidosis (ATTRwt) and 111 (39%) light-chain amyloidosis (AL)-were consecutively enrolled between December 2010 and September 2019. Transthoracic echocardiographies at time of diagnosis were reviewed to establish the presence and severity of TR and its relationship with all-cause mortality during patients' follow-up. Seventy-four (26%) patients had a moderate-to-severe TR. Moderate-to-severe TR was associated with New York Heart Association status (P < 0.001), atrial fibrillation (P = 0.003), greater levels of natriuretic peptides (P = 0.002), worst renal function (P = 0.03), lower left ventricular ejection fraction (P = 0.02), reduced right ventricular systolic function (P = 0.001), thicker tricuspid leaflets (P = 0.019), greater tricuspid annulus diameter (P = 0.001), greater pulmonary artery pressure (P = 0.001), greater doses of furosemide (P = 0.001), and anti-aldosterone (P = 0.01) and more anticoagulant treatment (P = 0.001). One hundred and thirty-four (47%) patients met the primary endpoint of all-cause mortality. After multivariate Cox analysis, moderate-to-severe TR was significantly associated with mortality [hazard ratio 1.89, 95% confidence interval (1.01-3.51), P = 0.044] in patients with ATTRwt. There was no correlation between TR and death [hazard ratio 0.84, 95% confidence interval (0.46-1.51), P = 0.562] in patients with AL. CONCLUSIONS: Moderate-to-severe TR is frequent in CA, and it is an independent prognosis factor in patients with ATTRwt but not in patients with AL.

New Oral Anticoagulants vs. Vitamin K Antagonists Among Patients With Cardiac Amyloidosis: Prognostic Impact.

Background: Atrial arrhythmia (AA) is common among patients with cardiac amyloidosis (CA), who have an increased risk of intracardiac thrombus. The aim of this study was to explore the prognostic impact of vitamin K-antagonists (VKA) and direct oral anticoagulants (DOAC) in patients with CA. Methods and Results: 273 patients with CA and history of AA with long term anticoagulation-69 (25%) light chain amyloidosis (AL), 179 (66%) wild-type transthyretin amyloidosis (ATTRwt) and 25 (9%) variant transthyretin amyloidosis (ATTRv)-were retrospectively included between January 2012 and July 2020. 147 (54%) and 126 (46%) patients received VKA and DOAC, respectively. Patient receiving VKA were more likely to have AL with renal dysfunction, higher NT-proBNP and troponin levels. Patients with ATTRwt were more likely to receive DOAC therapy. There were more bleeding complications among patients with VKA (20 versus 10%; P = 0.013) but no difference for stroke events (4 vs. 2%; P = 0.223), as compared to patients with DOAC. A total of 124 (45%) patients met the primary endpoint of all-cause mortality: 96 (65%) and 28 (22%) among patients with VKAs and DOACs, respectively (P < 0.001). After multivariate analysis including age and renal function, VKA was no longer associated with all-cause mortality. Conclusion: Among patients with CA and history of AA receiving oral anticoagulant, DOACs appear to be at least as effective and safe as VKAs.