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Objectives Measures of right heart size and function are prognostic in systemic sclerosis-associated pulmonary hypertension (SSc-PH), but the importance of myocardial tissue characterisation remains unclear. We aimed to investigate the predictive potential and interaction of cardiovascular magnetic resonance (CMR) myocardial tissue characterisation and right heart size and function in SSc-PH. Methods A retrospective, single-centre, observational study of 148 SSc-PH patients confirmed by right heart catheterization who underwent clinically indicated CMR including native myocardial T1 and T2 mapping from 2016 to 2023 was performed. Results Sixty-six (45%) patients died during follow-up (median 3.5 years, range 0.1–7.3). Patients who died were older (65 vs 60 years, P  = 0.035) with more dilated (P  < 0.001), hypertrophied (P  = 0.013) and impaired (P  < 0.001) right ventricles, more dilated right atria (P  = 0.043) and higher native myocardial T1 (P  < 0.001). After adjustment for age, indexed right ventricular end-systolic volume (RVESVi, P  = 0.0023) and native T1 (P  = 0.0024) were independent predictors of all-cause mortality. Both RVESVi and native T1 remained independently predictive after adjusting for age and PH subtype (RVESVi P  < 0.001, T1 P  = 0.0056). Optimal prognostic thresholds for RVESVi and native T1 were ≤38 mL/m2 and ≤1119 ms, respectively (P  < 0.001). Patients with RVESVi ≤ 38 mL/m2 and native T1 ≤ 1119 ms had significantly better outcomes than all other combinations (P  < 0.001). Furthermore, patients with RVESVi > 38mL/m2 and native T1 ≤ 1119 ms had significantly better survival than patients with RVESVi > 38mL/m2 and native T1 > 1119ms (P  = 0.017). Conclusion We identified prognostically relevant CMR metrics and thresholds for patients with SSc-PH. Assessing myocardial tissue characterisation alongside right ventricular function confers added value in SSc-PH and may represent an additional treatment target. [ABSTRACT FROM AUTHOR]

Aims: Transthyretin cardiac amyloidosis (ATTR‐CA) is stratified into prognostic categories using the National Amyloidosis Centre (NAC) staging system. The aims of this study were to further expand the existing NAC staging system to incorporate an additional disease stage that would identify patients at high risk of early mortality. Methods and results: The traditional NAC staging system (stage 1: N‐terminal pro‐B‐type natriuretic peptide [NT‐proBNP] ≤3000 ng/L and estimated glomerular filtration rate [eGFR] ≥45 ml/min; stage 3: NT‐proBNP >3000 ng/L and eGFR <45 ml/min; stage 2: remainder) was expanded by the introduction of a new stage 4 (defined as NT‐proBNP ≥10 000 ng/L irrespective of eGFR) and studied in 2042 patients. The optimal NT‐proBNP cut‐point was established using time‐dependent receiver operating characteristic curves in the subgroup of patients with NAC stage 3 disease. Mortality at 1 year according to NAC stage was 2.3% (n = 20/886) for stage 1, 8.8% (n = 62/706) for stage 2, 10.4% (n = 28/270) for stage 3, and 30.6% (n = 55/180) for stage 4 (log‐rank p < 0.001). After adjustment for age, mortality hazard for stage 4 was >15‐fold higher than that of stage 1 (hazard ratio [HR] 15.5; 95% confidence interval [CI] 9.3–26.1) and >3‐fold higher than that of stage 3 (HR 3.4; 95% CI 2.2–5.4). The increased risk of early mortality was consistent across the different genotypes and subclasses of patients based on the severity of heart failure symptoms and echocardiographic parameters. Conclusions: The proposed modification of the NAC staging system identifies patients with ATTR‐CA at a high risk of early mortality, who may benefit from a more intensive treatment strategy, and who are most likely to experience an event early in the course of a clinical trial. [ABSTRACT FROM AUTHOR]

Aims: Transthyretin amyloid cardiomyopathy (ATTR‐CM) is an increasingly recognized cause of heart failure. A total of 3–4% of individuals of African descent carry a TTR gene mutation encoding the p.(V142I) variant, a powerful risk factor for development of variant ATTR‐CM (ATTRv‐CM); this equates to 1.6 million carriers in the United States. We undertook deep phenotyping of p.(V142I)‐ATTRv‐CM and comparison with wild‐type ATTR‐CM (ATTRwt‐CM). Methods and results: A retrospective study of 413 patients with p.(V142I) ATTRv‐CM who attended the UK National Amyloidosis Centre (NAC) was conducted. Patients underwent evaluation at time of diagnosis, including clinical, echocardiography, and biomarker analysis; a subgroup had cardiac magnetic resonance (CMR) imaging. A total of 413 patients with ATTRwt‐CM, matched for independent predictors of prognosis (age, NAC Stage, decade of first presentation), were used as a comparator group. At time of diagnosis, patients with ATTRv‐CM had significant functional impairment by New York Heart Association classification (NHYA class ≥ III; 38%) and 6‐min walk test distance (median 276 m). Median 5‐year survival in ATTRv‐CM patients was 31 versus 59 months in matched patients with ATTRwt‐CM (p < 0.001). Patients with ATTRv‐CM had significant impairment of functional parameters by echocardiography including biventricular impairment, high burden of regurgitant valvular disease and low cardiac output. Multivariable analysis revealed the prognostic importance of right ventricular dysfunction. CMR and histological analysis revealed myocyte atrophy and widespread myocardial infiltration in ATTRv‐CM. Conclusion: p.(V142I)‐ATTRv‐CM has an aggressive phenotype characterized by myocyte loss and widespread myocardial infiltration which may account for frequent biventricular failure and poor prognosis in this ATTR‐CM genotypic subgroup. [ABSTRACT FROM AUTHOR]

Aims: Transthyretin cardiac amyloidosis (ATTR‐CA) is an infiltrative cardiomyopathy that commonly presents with concomitant chronic kidney disease. Albuminuria is common in heart failure and associated with worse outcomes, but its prevalence and relationship to outcome in ATTR‐CA remains unclear. Methods and results: A total of 1181 patients with ATTR‐CA were studied (mean age 78.1 ± 7.9 years; 1022 [86.5%] male; median estimated glomerular filtration rate 59 ml/min/1.73m2 [interquartile range: 47–74]). Albuminuria was present in 563 (47.7%) patients (499 [88.6%] with microalbuminuria and 64 [11.4%] with macroalbuminuria). Patients with albuminuria had a more severe cardiac phenotype evidenced by higher serum cardiac biomarkers (median N‐terminal pro‐B‐type natriuretic peptide [NT‐proBNP]: 4027 ng/L [2173–6889] vs. 1851 ng/L [997–3209], p < 0.001; median troponin T: 69 ng/L [46–101] vs. 48 ng/L [34–68], p < 0.001) and worse echocardiographic indices of systolic (longitudinal strain: −10.0 ± 3.6% vs. −11.6 ± 3.8%, p < 0.001) and diastolic function (E/e′: 17.5 ± 6.4 vs. 16.4 ± 6.7, p < 0.001) than those with a normal urinary albumin to creatinine ratio (UACR). Microalbuminuria and macroalbuminuria were independently associated with mortality in the overall population (hazard ratio [HR] 1.47, 95% confidence interval [CI] 1.13–1.92, p = 0.005 and HR 1.87, 95% CI 1.15–3.05, p = 0.012, respectively). In a subgroup of patients (n = 349) without concomitant hypertension, diabetes mellitus or chronic kidney disease, albuminuria was also associated with mortality (HR 2.98, 95% CI 1.72–5.17, p < 0.001). At 12 months, 330 patients had a repeat UACR measurement; those in whom UACR increased by 30% or more (n = 148, 44.8%) had an increased risk of mortality (HR 1.84, 95% CI 1.06–3.19, p = 0.030). Conclusions: Albuminuria is common in patients with ATTR‐CA, and more prevalent in those with a more severe cardiac phenotype. Albuminuria at diagnosis and a significant increase in UACR during follow‐up are associated with mortality. [ABSTRACT FROM AUTHOR]

Aims Cardiovascular involvement in systemic sclerosis (SSc) is heterogeneous and ill-defined. This study aimed to: (i) discover cardiac phenotypes in SSc by cardiovascular magnetic resonance (CMR); (ii) provide a CMR-based algorithm for phenotypic classification; and (iii) examine for associations between phenotypes and mortality. Methods and results A retrospective, single-centre, observational study of 260 SSc patients who underwent clinically indicated CMR including native myocardial T1 and T2 mapping from 2016 to 2019 was performed. Agglomerative hierarchical clustering using only CMR variables revealed five clusters of SSc patients with shared CMR characteristics: dilated right hearts with right ventricular failure (RVF); biventricular failure dilatation and dysfunction (BVF); and normal function with average cavity (NF-AC), normal function with small cavity (NF-SC), and normal function with large cavity (NF-LC) sizes. Phenotypes did not co-segregate with clinical or antibody classifications. A CMR-based decision tree for phenotype classification was created. Sixty-three (24%) patients died during a median follow-up period of 3.4 years. After adjustment for age and presence of pulmonary hypertension (PH), independent CMR predictors of all-cause mortality were native T1 (P < 0.001) and right ventricular ejection fraction (RVEF) (P = 0.0032). NF-SC and NF-AC groups had more favourable prognoses (P ≤0.036) than the other three groups which had no differences in prognoses between them (P > 0.14). Hazard ratios (HR) were statistically significant for RVF (HR = 8.9, P < 0.001), BVF (HR = 5.2, P = 0.006), and NF-LC (HR = 4.9, P = 0.002) groups. The NF-LC group remained significantly predictive of mortality after adjusting for RVEF, native T1, and PH diagnosis (P = 0.0046). Conclusion We identified five CMR-defined cardiac SSc phenotypes that did not co-segregate with clinical data and had distinct outcomes, offering opportunities for a more precision-medicine based management approach. [ABSTRACT FROM AUTHOR]

SUMMARY: Second-generation antipsychotic medications (SGAs) have advanced the treatment of schizophrenia over the past 30 years. However, a number of potentially life-threatening cardiac side-effects associated with these treatments concern and can discourage prescribers from administering these evidence-based treatments. This review provides a practical, psychiatrist-oriented understanding of the relative frequencies, mechanisms, investigations and treatments associated with these cardiac toxicities. We aim to highlight that these are relatively rare complications of an effective class of drug and to promote the advantages of early involvement of cardiologists in the psychiatric multidisciplinary team to guide the investigation and management of these conditions. LEARNING OBJECTIVES: After reading this article you will be able to: • understand the relative incidence of cardiotoxic side-effects of the various SGAs • perform preliminary investigations to diagnose the common cardiotoxic side-effects of SGAs • understand the treatments for these cardiac side-effects and the role of cardiologists involved the care of these patients. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusions Cardiac amyloidosis (CA) is characterized by deposition of amyloid fibrils within the extracellular space, causing disarray of the myocardial structure and capillary architecture. This study aims to characterize the prevalence of microvascular obstruction (MVO) in patients with CA and to assess the association between MVO and prognosis.The study population comprised 800 patients, of which 400 had light‐chain CA (AL‐CA) and 400 had transthyretin CA (ATTR‐CA). MVO was present in 221 (27.6%) patients, and more common in ATTR‐CA than AL‐CA (124 [56.1%] vs. 97 [43.9%], p = 0.033). Patients with MVO had a more severe cardiac phenotype evidenced by higher N‐terminal pro‐brain natriuretic peptide (3516 ng/L [1944–6247] vs. 2508 ng/L [1203–5752], p < 0.001), worse global longitudinal strain (−10.5% [−12.6; −7.9] vs. −12.0% [−16.0; −8.9], p < 0.001), and higher extracellular volume (56% [51–61] vs. 50% [45–57], p < 0.001). Patients with AL‐CA and MVO had a higher serum troponin (86 ng/L [47–148] vs. 59 ng/L [44–78], p < 0.001), and higher T2 (53 ms [50–56] vs. 50 ms [48–52], p < 0.001), but lower extracellular volume (55% [50–60] vs. 58% [53–61], p = 0.008) and lower indexed myocyte cell volume (48.6 g/m2 [41.1–59.8] vs. 55.7 g/m2 [47.5–68.4], p < 0.001) than patients with ATTR‐CA and MVO. MVO was associated with an increased risk of mortality in the overall population (hazard ratio [HR] 1.28, 95% confidence interval [CI] 1.03–1.59, p = 0.025), and the subgroup with AL‐CA (HR 1.59, 95% CI 1.17–2.17, p = 0.003) but not ATTR‐CA (HR 1.04, 95% CI 0.77–1.40, p = 0.814).Microvascular obstruction is common in CA and is related to markers of amyloid infiltration. MVO is associated with an increased risk of mortality in AL‐CA, but not in ATTR‐CA. This reflects the intrinsic differences in disease biology between these two forms of CA, with MVO likely related to multiple myocardial processes, amyloid infiltration, oedema and myocyte death. [ABSTRACT FROM AUTHOR]

Background: Transthyretin cardiac amyloidosis (ATTR-CA) is a progressive cardiomyopathy. The clinical course varies among individuals and there are no established measures to assess disease progression., Objectives: The goal of this study was to assess the prognostic importance of an increase in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and outpatient diuretic intensification (ODI) as markers of disease progression in a large cohort of patients with ATTR-CA., Methods: We evaluated landmark survival analysis based on worsening of NT-proBNP and requirement for ODI between time of diagnosis and a 1-year visit, and subsequent mortality in 2,275 patients with ATTR-CA from 7 specialist centers. The variables were developed in the National Amyloidosis Centre (NAC) cohort (n = 1,598) and validated in the external cohort from the remaining centers (n = 677)., Results: Between baseline and 1-year visits, 551 (34.5%) NAC patients and 204 (30.1%) patients in the external validation cohort experienced NT-proBNP progression (NT-proBNP increase >700 ng/L and >30%), which was associated with mortality (NAC cohort: HR: 1.82; 95% CI: 1.57-2.10; P < 0.001; validation cohort: HR: 1.75; 95% CI: 1.32-2.33; P < 0.001). At 1 year, 451 (28.2%) NAC patients and 301 (44.5%) patients in the external validation cohort experienced ODI, which was associated with mortality (NAC cohort: HR: 1.88; 95% CI: 1.62-2.18; P < 0.001; validation cohort: HR: 2.05; 95% CI: 1.53-2.74; P < 0.001). When compared with patients with a stable NT-proBNP and stable diuretic dose, a higher risk of mortality was observed in those experiencing either NT-proBNP progression or ODI (NAC cohort: HR: 1.93; 95% CI: 1.65-2.27; P < 0.001; validation cohort: HR: 1.94; 95% CI: 1.36-2.77; P < 0.001), and those experiencing both NT-proBNP progression and ODI (NAC cohort: HR: 2.98; 95% CI: 2.42-3.67; P < 0.001; validation cohort: HR: 3.23; 95% CI: 2.17-4.79; P < 0.001)., Conclusions: NT-proBNP progression and ODI are frequent and consistently associated with an increased risk of mortality. Combining both variables produces a simple, universally applicable model that detects disease progression in ATTR-CA., Competing Interests: Funding Support and Author Disclosures Dr Fontana is supported by a British Heart Foundation Intermediate Clinical Research Fellowship (FS/18/21/33447); and has received consulting income from Intellia, Novo Nordisk, Pfizer, Eidos, Prothena, Akcea, Alnylam, Caleum, Alexion, Janssen, Ionis, and AstraZeneca. Dr Gilmore has received consulting income from Ionis, Eidos, Intellia, Alnylam, and Pfizer. Dr Wechalekar has received consulting income from Alexia, AstraZeneca, Janssen, Attralus, and Prothena. Dr Cappelli has received consulting income from Alnylam, Pfizer, AstraZeneca, Bridgebio, and Novo Nordisk. Dr Cipriani has received consulting income from AstraZeneca. Dr Solomon has received research grants from Alexion, Alnylam, AstraZeneca, Bellerophon, Bayer, BMS, Cytokinetics, Eidos, Gossamer, GSK, Ionis, Lilly, MyoKardia, National Institutes of Health/National Heart, Lung, and Blood Institute, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, and US2.AI; and has served as a consultant for Abbott, Action, Akros, Alexion, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boeringer Ingelheim, BMS, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GSK, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, and Valo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: Cardiovascular involvement in systemic sclerosis (SSc) is heterogeneous and ill-defined. This study aimed to: (i) discover cardiac phenotypes in SSc by cardiovascular magnetic resonance (CMR); (ii) provide a CMR-based algorithm for phenotypic classification; and (iii) examine for associations between phenotypes and mortality., Methods and Results: A retrospective, single-centre, observational study of 260 SSc patients who underwent clinically indicated CMR including native myocardial T1 and T2 mapping from 2016 to 2019 was performed. Agglomerative hierarchical clustering using only CMR variables revealed five clusters of SSc patients with shared CMR characteristics: dilated right hearts with right ventricular failure (RVF); biventricular failure dilatation and dysfunction (BVF); and normal function with average cavity (NF-AC), normal function with small cavity (NF-SC), and normal function with large cavity (NF-LC) sizes. Phenotypes did not co-segregate with clinical or antibody classifications. A CMR-based decision tree for phenotype classification was created. Sixty-three (24%) patients died during a median follow-up period of 3.4 years. After adjustment for age and presence of pulmonary hypertension (PH), independent CMR predictors of all-cause mortality were native T1 (P < 0.001) and right ventricular ejection fraction (RVEF) (P = 0.0032). NF-SC and NF-AC groups had more favourable prognoses (P≤0.036) than the other three groups which had no differences in prognoses between them (P > 0.14). Hazard ratios (HR) were statistically significant for RVF (HR = 8.9, P < 0.001), BVF (HR = 5.2, P = 0.006), and NF-LC (HR = 4.9, P = 0.002) groups. The NF-LC group remained significantly predictive of mortality after adjusting for RVEF, native T1, and PH diagnosis (P = 0.0046)., Conclusion: We identified five CMR-defined cardiac SSc phenotypes that did not co-segregate with clinical data and had distinct outcomes, offering opportunities for a more precision-medicine based management approach., Competing Interests: Conflict of interest: The authors declare that there are no conflicts of interest in relation to the work in this manuscript. Non-conflicting relationships with industry are as follows: D.S.K. reports consulting fees, speaker bureau fees and research funding from Johnson & Johnson. A.M.S-R. reports sponsorship from Janssen, Abbvie and Pfizer. B.E.S. reports consulting fees, speaker bureau fees and research funding from Johnson & Johnson, and speaker fees from GSK. C.P.D. reports personal fees from Acceleron, Corbus, Boehringer Ingelheim, Horizon, Johnson & Johnson, Roche, Sanofi, and grants and personal fees from CSL Behrin, GSK and Inventiva. J.G.C. reports consulting fees from Acceleron, consulting and speaker bureau fees from Bayer, GSK and Johnson & Johnson, and research funding from Johnson & Johnson., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)