Ongoing Exercise Intolerance Following COVID‐19: A Magnetic Resonance–Augmented Cardiopulmonary Exercise Test Study

Background: Ongoing exercise intolerance of unclear cause following COVID‐19 infection is well recognized but poorly understood. We investigated exercise capacity in patients previously hospitalized with COVID‐19 with and without self‐reported exercise intolerance using magnetic resonance–augmented cardiopulmonary exercise testing. / Methods and Results: Sixty subjects were enrolled in this single‐center prospective observational case‐control study, split into 3 equally sized groups: 2 groups of age‐, sex‐, and comorbidity‐matched previously hospitalized patients following COVID‐19 without clearly identifiable postviral complications and with either self‐reported reduced (COVIDreduced) or fully recovered (COVIDnormal) exercise capacity; a group of age‐ and sex‐matched healthy controls. The COVIDreducedgroup had the lowest peak workload (79W [Interquartile range (IQR), 65–100] versus controls 104W [IQR, 86–148]; P=0.01) and shortest exercise duration (13.3±2.8 minutes versus controls 16.6±3.5 minutes; P=0.008), with no differences in these parameters between COVIDnormal patients and controls. The COVIDreduced group had: (1) the lowest peak indexed oxygen uptake (14.9 mL/minper kg [IQR, 13.1–16.2]) versus controls (22.3 mL/min per kg [IQR, 16.9–27.6]; P=0.003) and COVIDnormal patients (19.1 mL/min per kg [IQR, 15.4–23.7]; P=0.04); (2) the lowest peak indexed cardiac output (4.7±1.2 L/min per m2) versus controls (6.0±1.2 L/min per m2; P=0.004) and COVIDnormal patients (5.7±1.5 L/min per m2; P=0.02), associated with lower indexed stroke volume (SVi:COVIDreduced 39±10 mL/min per m2 versus COVIDnormal 43±7 mL/min per m2 versus controls 48±10 mL/min per m2; P=0.02). There were no differences in peak tissue oxygen extraction or biventricular ejection fractions between groups. There were no associations between COVID‐19 illness severity and peak magnetic resonance–augmented cardiopulmonary exercise testing metrics. Peak indexed oxygen uptake, indexed cardiac output, and indexed stroke volume all correlated with duration from discharge to magnetic resonance–augmented cardiopulmonary exercise testing (P<0.05). / Conclusions: Magnetic resonance–augmented cardiopulmonary exercise testing suggests failure to augment stroke volume as a potential mechanism of exercise intolerance in previously hospitalized patients with COVID‐19. This is unrelated to disease severity and, reassuringly, improves with time from acute illness

Rare Forms of Cardiac Amyloidosis: Diagnostic Clues and Phenotype in Apo AI and AIV Amyloidosis

BACKGROUND: Apo AI amyloidosis (AApoAI) and Apo AIV amyloidosis (AApoAIV) are rare but increasingly recognized causes of cardiac amyloidosis (CA). We sought to define the cardiac phenotype in AApoAI and AApoAIV using multimodality imaging. METHODS: We identified all patients with AApoAI and AApoAIV assessed at our center between 2000 and 2021, and 2 cohorts of patients with immunoglobulin light-chain amyloidosis (AL) and transthyretin amyloidosis matched for age, sex, and cardiac involvement. RESULTS: Forty-five patients had AApoAI, 13 (29%) of whom had cardiac involvement, 32 (71%) renal involvement, 28 (62%) splenic involvement, 27 (60%) hepatic involvement, and 7 (16%) laryngeal involvement. AApoAI-CA commonly presented with heart failure (n=8, 62%) or dysphonia (n=7, 54%). The Arg173Pro variant universally caused cardiac and laryngeal involvement (n=7, 100%). AApoAI-CA was associated with right-sided involvement, with a thicker right ventricular free wall (8.6±1.9 versus 6.3±1.3 mm versus 7.7±1.2 mm, P=0.004), greater incidence of tricuspid stenosis (4 [31%] versus 0 [0%] versus 0 [0%], P=0.012) and tricuspid regurgitation (6 [46%] versus 1 [8%] versus 2 [15%], P=0.048) than AL-CA and transthyretin CA. Twenty-one patients had AApoAIV, and cardiac involvement was more common than in AApoAI (15 [71%] versus 13 [29%], P=0.001). AApoAIV-CA most commonly presented with heart failure (n=12, 80%), and a lower median estimated glomerular filtration rate than AL-CA and transthyretin CA (36 mL/[min·1.73 m²] versus 65 mL/[min·1.73 m²] versus 63 mL/[min·1.73 m²], P172 and >30 months, respectively), and a lower risk of mortality than matched patients with AL-amyloidosis (AL versus AApoAI: hazard ratio, 4.54 [95% CI, 2.02-10.14]; P<0.001; AL versus AApoAIV: hazard ratio, 3.07 [95% CI, 1.27-7.44]; P=0.013). CONCLUSIONS: Dysphonia, multisystem involvement, or right-sided cardiac disease should raise suspicion of AApoAI-CA. AApoAIV-CA presents most commonly with heart failure and always displays classical CA imaging features, mimicking common forms of CA. Both AApoAI and AApoAIV are associated with a good prognosis and a lower risk of mortality than matched patients with AL-amyloidosis

External electrical and pharmacological cardioversion for atrial fibrillation, atrial flutter or atrial tachycardias:a network meta-analysis

BackgroundAtrial fibrillation (AF) is the most frequent sustained arrhythmia. Cardioversion is a rhythm control strategy torestore normal/sinus rhythm, and can be achieved through drugs (pharmacological) or a synchronized electricshock (electrical cardioversion).ObjectivesTo assess the efficacy and safety of pharmacological and electrical cardioversion for AF.Search methodsWe searched CENTRAL, MEDLINE, Embase, Conference Proceedings Citation Index-Science (CPCI-S) andthree trials registers (ClinicalTrials.gov, WHO ICTRP and ISRCTN) on 14 February 2023.Selection criteriaWe included randomised controlled trials (RCTs) at individual patient level. Patient populations were aged ≥18years with AF of any type and duration, atrial flutter or other sustained related atrial arrhythmias, not occurring asa result of reversible causes.Data collection and analysisWe used standard Cochrane methodology to collect data and performed a network meta-analysis using thestandard frequentist graph-theoretical approach using the netmeta package in R. We used GRADE to assess thequality of the evidence which we presented in in our summary of findings with a judgement on certainty. Wecalculated differences using risk ratios (RR) and 95% confidence intervals (CI) as well as ranking treatmentsusing a P-score. We assessed clinical and statistical heterogeneity and split the networks for the primaryoutcome and acute procedural success due to concerns about violating the transitivity assumption.Main resultsWe included 112 RCTs (139 records), from which we pooled data from 15,968 patients. Average age was 47 to72 years and proportion of male patients was 38%-92%.79 trials were considered high risk of bias for at least one domain, 32 had no high risk of bias domains, but hadat least one domain classified as uncertain risk, and one study was considered low risk for all domains.For paroxysmal AF (35 trials), when compared to Placebo, AA/AP BTE incremental cardioversion (RR: 2.42;95%CI 1.65 to 3.56), quinidine (RR: 2.23; 95%CI 1.49 to 3.34), ibutilide (RR: 2.00; 95%CI 1.28 to 3.12),propafenone (RR: 1.98; 95%CI 1.67 to 2.34), amiodarone (RR: 1.69; 95%CI 1.42 to 2.02), sotalol (RR: 1.58;95%CI 1.08 to 2.31) and procainamide (RR: 1.49; 95%CI 1.13 to 1.97) likely result in a large increase inmaintenance of sinus rhythm until hospital discharge or end of study follow-up (certainty of evidence: moderate).The effect size was larger for AA/AP incremental and was progressively smaller for the subsequent interventions.Despite low certainty of evidence Antazoline may result in a large increase (RR: 28.60; 95%CI 1.77 to 461.30) inthis outcome. Similarly, low certainty evidence suggests a large increase on this outcome for flecainide (RR: 2.17;95%CI 1.68 to 2.79), vernakalant (RR: 2.13; 95%CI 1.52 to 2.99), and magnesium (RR: 1.73; 95%CI 0.79 to 3.79)on this outcome.For persistent AF (26 trials), one network was created for electrical cardioversion and showed that whencompared to AP BTE incremental energy with patches, AP BTE maximum energy with patches (RR 1.35, 95%CI1.17 to 1.55) likely results in large increase and Active compression AP BTE incremental energy with patches(RR: 1.14, 95%CI 1.00 to 1.131) likely results in an increase in maintenance of sinus rhythm at hospital dischargeor end of study follow-up (certainty of evidence: high). Use of AP BTE incremental with paddles (RR: 1.03, 95%CI0.98 to 1.09; certainty of evidence: low) may lead to a little increase, and AP MDS Incremental paddles (RR: 0.95,95%CI 0.86 to 1.05; certainty of evidence: low) may lead to a little decrease in efficacy. On the other hand, APMDS incremental energy using patches (RR: 0.78, 95%CI 0.70 to 0.87), AA RBW incremental energy withpatches (RR: 0.76, 95%CI 0.66 to 0.88), AP RBW incremental energy with patches (RR: 0.76, 95%CI 0.68 to0.86), AA MDS incremental energy with patches (RR: 0.76, 95%CI 0.67 to 0.86) and AA MDS incremental energywith paddles (RR: 0.68, 95%CI 0.53 to 0.83) probably result in a decrease on this outcome when compared to APBTE incremental energy with patches (certainty of evidence: moderate). The network for pharmacologicalcardioversion showed that Bepridil (RR: 2.29, 95%CI 1.26 to 4.17) and Quindine (RR: 1.53, (95%CI 1.01 to 2.32)probably result in large increase in maintenance of sinus rhythm at hospital discharge or end of study follow-upwhen compared to amiodarone (certainty of evidence: moderate). Dofetilide (RR: 0.79, 95%CI 0.56 to 1.44),Sotalol (RR: 0.89, 95%CI 0.67 to 1.18), Propafenone (RR: 0.79, 95%CI 0.50 to 1.25) and Pilsicainide (RR: 0.39,95%CI 0.02 to 7.01) may result in a reduction of this outcome when compared to amiodarone, but certainty ofevidence is lowFor atrial flutter (14 trials) a network could be created only for antiarrhythmic drugs. Using Placebo as thecommon comparator, ibutilide (RR: 21.45, 95%CI 4.41 to 104.37), propafenone (RR: 7.15, 95%CI 1.27 to 40.10),dofetilide (RR: 6.43, 95%CI 1.38 to 29.91), and sotalol (RR: 6.39, 95%CI 1.03 to 39.78) probably result in a largeincrease in maintenance of sinus rhythm at hospital discharge or end of study follow-up (certainty of evidence:moderate), and procainamide (RR: 4.29, 95%CI 0.63 to 29.03), flecainide (RR 3.57, 95%CI 0.24 to 52.30) andvernakalant (RR: 1.18, 95%CI 0.05 to 27.37) may result in a large increase of maintenance of sinus rhythm athospital discharge or end of study follow-up at (certainty of evidence: low) All tested electrical cardioversionstrategies for atrial flutter had very high efficacy (97.9% to 100%).Mortality (14 deaths) and Stroke or systemic embolism (3 events) at 30 days was extremely low.Data on quality of life were scarce and of uncertain clinical significance. No information was available regardingheart failure readmissions. Data on duration of hospitalization was scarce, low quality, &amp; could not be pooled.Authors' conclusionsDespite the low quality of evidence, this systematic review provides important information on electrical andpharmacological strategies to help patients and physicians deal with AF and atrial flutter.Assessing the patient comorbidity profile, antiarrhythmic drug onset of action &amp; side effect profile vs. need for aphysician with experience in sedation, or anaesthetics support, for electrical cardioversion are key aspects whenchoosing the cardioversion method

Prognostic Value of a 6-Minute Walk Test in Patients With Transthyretin Cardiac Amyloidosis

Background The 6-minute walk test (6MWT) represents a comprehensive functional assessment that is commonly used in patients with heart failure; however, data are lacking in patients with transthyretin cardiac amyloidosis (ATTR-CA). Objectives This study aimed to assess the prognostic importance of the 6MWT in patients with ATTR-CA.Methods A retrospective analysis of patients diagnosed with ATTR-CA at the National Amyloidosis Centre who underwent a baseline 6MWT between 2011 and 2023 identified 2,141 patients, of whom 1,118 had follow-up at 1 year.Results The median baseline 6MWT distance was 347 m (Q1-Q3: 250-428 m) and analysis by quartiles demonstrated an increased death rate with each distance reduction (deaths per 100 person-years: 6.3 vs 9.2 vs 13.6 vs 19.0; log-rank P &lt; 0.001). A 6MWT distance of 35 m) and relative worsening (reduction of &gt;5%) of 6MWT at 1 year was associated with an increased risk of mortality (HR: 1.80; 95% CI: 1.51-2.15; P &lt; 0.001 and HR: 1.89; 95% CI: 1.59-2.24; P &lt; 0.001, respectively), which was similar across the aforementioned subgroups. When combined with established measures of disease progression (N-terminal pro–B-type natriuretic peptide progression and outpatient diuretic intensification), each incremental increase in progression markers was associated with an increased death rate (deaths per 100 person-years: 7.6 vs 13.9 vs 22.4 vs 32.9; log-rank P &lt; 0.001). Conclusions The baseline 6MWT distance can refine risk stratification beyond traditional prognosticators. A worsening 6MWT distance can stratify disease progression and, when combined with established markers, identifies patients at the highest risk of mortality

Multi-Imaging Characterization of Cardiac Phenotype in Different Types of Amyloidosis

BACKGROUND: Bone scintigraphy is extremely valuable when assessing patients with suspected cardiac amyloidosis (CA), but the clinical significance and associated phenotype of different degrees of cardiac uptake across different types is yet to be defined. OBJECTIVES: This study sought to define the phenotypes of patients with varying degrees of cardiac uptake on bone scintigraphy, across multiple types of systemic amyloidosis, using extensive characterization comprising biomarkers as well as echocardiographic and cardiac magnetic resonance (CMR) imaging. METHODS: A total of 296 patients (117 with immunoglobulin light-chain amyloidosis [AL], 165 with transthyretin (TTR) amyloidosis [ATTR], 7 with apolipoprotein AI amyloidosis [AApoAI], and 7 with apolipoprotein AIV amyloidosis [AApoAIV]) underwent deep characterization of their cardiac phenotype. RESULTS: AL patients with grade 0 myocardial radiotracer uptake spanned the spectrum of CMR findings from no CA to characteristic CA, whereas AL patients with grades 1 to 3 always produced characteristic CMR features. In ATTR, the CA burden strongly correlated with myocardial tracer uptake, except in Ser77Tyr. AApoAI presented with grade 0 or 1 and disproportionate right-sided involvement. AApoAIV always presented with grade 0 and characteristic CA. AL grade 1 patients (n = 48; 100%) had characteristic CA, whereas only ATTR grade 1 patients with Ser77Tyr had characteristic CA on CMR (n = 5; 11.4%). After exclusion of Ser77Tyr, AApoAI, and AApoAIV, CMR showing characteristic CA or an extracellular volume of >0.40 in patients with grade 0 to 1 cardiac uptake had a sensitivity and specificity of 100% for AL. CONCLUSIONS: There is a wide variation in cardiac phenotype between different amyloidosis types across different degrees of cardiac uptake. The combination of CMR and bone scintigraphy can help to define the diagnostic differentials and the clinical phenotype in each individual patient

Prevalence, Characteristics and Outcomes of Older Patients with Hereditary versus Wild-Type Transthyretin Amyloid Cardiomyopathy

BACKGROUND: Transthyretin amyloid cardiomyopathy (ATTR-CM) is often assumed to be associated with wild-type TTR genotype (ATTRwt) in elderly patients (aged >70), some of whom are not offered genetic testing. We sought to estimate the prevalence, clinical characteristics and prognostic implications of TTR variants among elderly patients diagnosed with ATTR-CM. METHODS: Data from consecutive patients over 70 years of age diagnosed with ATTR-CM at the UK National Amyloidosis Centre between January 2010 and August 2022 were retrospectively evaluated. All patients underwent clinical evaluation, biochemical tests, echocardiography and TTR genotyping. The study outcome was all-cause mortality. RESULTS: The study population consisted of 2029 patients with ATTR-CM (median age 79 years at diagnosis, 13.2% females, 80.4% Caucasian). Variant ATTR-CM (ATTRv-CM) was diagnosed in 20.7% (n=421) of the study population of whom 329 (76.3%) carried V122I, 49 (11.4%) T60A, 18 (4.2%) V30M and 35 (8.1%) other pathogenic TTR variants. During a median (range) follow up of 29 (12-48) months, ATTRv-CM was associated with increased all-cause mortality compared to ATTRwt-CM, with the poorest survival observed in V122I-associated ATTRv-CM (p<0.001). Univariable and multivariable logistic regression analyses in those with ATTR-CM showed younger age at diagnosis (odds ratio [OR] 0.85 per year, p<0.001), female sex (OR 2.73, p<0.001), Afro-Caribbean ethnicity (OR 65.5, p<0.001), atrial fibrillation (OR 0.65, p=0.015), ischemic heart disease (OR 0.54, p=0.007), peripheral polyneuropathy (OR 5.70, p<0.001) and orthostatic hypotension (OR 6.29, p<0.001) to be independently associated with ATTRv-CM. CONCLUSION: Up to 20.7% of elderly patients with ATTR-CM have a pathogenic TTR variant. These findings support routine sequencing of the TTR gene in all patients with ATTR-CM regardless of age. This article is protected by copyright. All rights reserved

Tracking Treatment Response in Cardiac Light-Chain Amyloidosis With Native T1 Mapping

IMPORTANCE: Cardiac magnetic resonance (CMR) imaging-derived extracellular volume (ECV) mapping, generated from precontrast and postcontrast T1, accurately determines treatment response in cardiac light-chain amyloidosis. Native T1 mapping, which can be derived without the need for contrast, has demonstrated accuracy in diagnosis and prognostication, but it is unclear whether serial native T1 measurements could also track the cardiac treatment response. OBJECTIVE: To assess whether native T1 mapping can measure the cardiac treatment response and the association between changes in native T1 and prognosis. DESIGN, SETTING, AND PARTICIPANTS: This single-center cohort study evaluated patients diagnosed with cardiac light-chain amyloidosis (January 2016 to December 2020) who underwent CMR scans at diagnosis and a repeat scan following chemotherapy. Analysis took place between January 2016 and October 2022. MAIN OUTCOMES AND MEASURES: Comparison of biomarkers and cardiac imaging parameters between patients with a reduced, stable, or increased native T1 and association between changes in native T1 and mortality. RESULTS: The study comprised 221 patients (mean [SD] age, 64.7 [10.6] years; 130 male [59%]). At 6 months, 183 patients (mean [SD] age, 64.8 [10.5] years; 110 male [60%]) underwent repeat CMR imaging. Reduced native T1 of 50 milliseconds or more occurred in 8 patients (4%), all of whom had a good hematological response; by contrast, an increased native T1 of 50 milliseconds or more occurred in 42 patients (23%), most of whom had a poor hematological response (27 [68%]). At 12 months, 160 patients (mean [SD] age, 63.8 [11.1] years; 94 male [59%]) had a repeat CMR scan. A reduced native T1 occurred in 24 patients (15%), all of whom had a good hematological response, and was associated with a reduction in N-terminal pro-brain natriuretic peptide (median [IQR], 2638 [913-5767] vs 423 [128-1777] ng/L; P < .001), maximal wall thickness (mean [SD], 14.8 [3.6] vs 13.6 [3.9] mm; P = .009), and E/e' (mean [SD], 14.9 [6.8] vs 12.0 [4.0]; P = .007), improved longitudinal strain (mean [SD], -14.8% [4.0%] vs -16.7% [4.0%]; P = .004), and reduction in both myocardial T2 (mean [SD], 52.3 [2.9] vs 49.4 [2.0] milliseconds; P < .001) and ECV (mean [SD], 0.47 [0.07] vs 0.42 [0.08]; P < .001). At 12 months, an increased native T1 occurred in 24 patients (15%), most of whom had a poor hematological response (17 [71%]), and was associated with an increased N-terminal pro-brain natriuretic peptide (median [IQR], 1622 [554-5487] vs 3150 [1161-8745] ng/L; P = .007), reduced left ventricular ejection fraction (mean [SD], 65.8% [11.4%] vs 61.5% [12.4%]; P = .009), and an increase in both myocardial T2 (mean [SD], 52.5 [2.7] vs 55.3 [4.2] milliseconds; P < .001) and ECV (mean [SD], 0.48 [0.09] vs 0.56 [0.09]; P < .001). Change in myocardial native T1 at 6 months was independently associated with mortality (hazard ratio, 2.41 [95% CI, 1.36-4.27]; P = .003). CONCLUSIONS AND RELEVANCE: Changes in native T1 in response to treatment, reflecting a composite of changes in T2 and ECV, are associated with in changes in traditional markers of cardiac response and associated with mortality. However, as a single-center study, these results require external validation in a larger cohort

Tracking Multiorgan Treatment Response in Systemic AL-Amyloidosis With Cardiac Magnetic Resonance Derived Extracellular Volume Mapping

Background: Systemic light chain amyloidosis is a multisystem disorder that commonly involves the heart, liver, and spleen. Cardiac magnetic resonance with extracellular volume (ECV) mapping provides a surrogate measure of the myocardial, liver, and spleen amyloid burden. Objectives: The purpose of this study was to assess multiorgan response to treatment using ECV mapping, and assess the association between multiorgan treatment response and prognosis. Methods: The authors identified 351 patients who underwent baseline serum amyloid-P-component (SAP) scintigraphy and cardiac magnetic resonance at diagnosis, of which 171 had follow-up imaging. Results: At diagnosis, ECV mapping demonstrated that 304 (87%) had cardiac involvement, 114 (33%) significant hepatic involvement, and 147 (42%) significant splenic involvement. Baseline myocardial and liver ECV independently predict mortality (myocardial HR: 1.03 [95% CI: 1.01-1.06]; P = 0.009; liver HR: 1.03; [95% CI: 1.01-1.05]; P = 0.001). Liver and spleen ECV correlated with amyloid load assessed by SAP scintigraphy (R = 0.751; P < 0.001; R = 0.765; P < 0.001, respectively). Serial measurements demonstrated ECV correctly identified changes in liver and spleen amyloid load derived from SAP scintigraphy in 85% and 82% of cases, respectively. At 6 months, more patients with a good hematologic response had liver (30%) and spleen (36%) ECV regression than myocardial regression (5%). By 12 months, more patients with a good response demonstrated myocardial regression (heart 32%, liver 30%, spleen 36%). Myocardial regression was associated with reduced median N-terminal pro-brain natriuretic peptide (P < 0.001), and liver regression with reduced median alkaline phosphatase (P = 0.001). Changes in myocardial and liver ECV, 6 months after initiating chemotherapy, independently predict mortality (myocardial HR: 1.11 [95% CI: 1.02-1.20]; P = 0.011; liver HR: 1.07 [95% CI: 1.01-1.13]; P = 0.014). Conclusions: Multiorgan ECV quantification accurately tracks treatment response and demonstrates different rates of organ regression, with the liver and spleen regressing more rapidly than the heart. Baseline myocardial and liver ECV and changes at 6 months independently predict mortality, even after adjusting for traditional predictors of prognosis

Distinct cardiovascular phenotypes are associated with prognosis in systemic sclerosis: a cardiovascular magnetic resonance study

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  0.14). 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