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 (COVID reduced ) or fully recovered (COVID normal ) exercise capacity; a group of age‐ and sex‐matched healthy controls. The COVID reduced group 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 COVID normal patients and controls. The COVID reduced 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 COVID normal 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 m 2 ) versus controls (6.0±1.2 L/min per m 2 ; P =0.004) and COVID normal patients (5.7±1.5 L/min per m 2 ; P =0.02), associated with lower indexed stroke volume (SVi:COVID reduced 39±10 mL/min per m 2 versus COVID normal 43±7 mL/min per m 2 versus controls 48±10 mL/min per m 2 ; 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.
Aims To assess the ability of cardiovascular magnetic resonance (CMR) to (i) measure changes in response to chemotherapy; (ii) assess the correlation between haematological response and changes in extracellular volume (ECV); and (iii) assess the association between changes in ECV and prognosis over and above existing predictors. Methods and results In total, 176 patients with cardiac AL amyloidosis were assessed using serial N-terminal pro-B-type natriuretic peptide (NT-proBNP), echocardiography, free light chains and CMR with T1 and ECV mapping at diagnosis and subsequently 6, 12, and 24 months after starting chemotherapy. Haematological response was graded as complete response (CR), very good partial response (VGPR), partial response (PR), or no response (NR). CMR response was graded by changes in ECV as progression (≥0.05 increase), stable (<0.05 change), or regression (≥0.05 decrease). At 6 months, CMR regression was observed in 3% (all CR/VGPR) and CMR progression in 32% (61% in PR/NR; 39% CR/VGPR). After 1 year, 22% had regression (all CR/VGPR), and 22% had progression (63% in PR/NR; 37% CR/VGPR). At 2 years, 38% had regression (all CR/VGPR), and 14% had progression (80% in PR/NR; 20% CR/VGPR). Thirty-six (25%) patients died during follow-up (40 ± 15 months); CMR response at 6 months predicted death (progression hazard ratio 3.82; 95% confidence interval 1.95–7.49; P < 0.001) and remained prognostic after adjusting for haematological response, NT-proBNP and longitudinal strain (P < 0.01). Conclusions Cardiac amyloid deposits frequently regress following chemotherapy, but only in patients who achieve CR or VGPR. Changes in ECV predict outcome after adjusting for known predictors.
Transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly diagnosed disease. Echocardiography is widely utilized, but studies to confirm the value of echocardiography for tracking changes over time are not available. We sought to describe (i) changes in multiple echocardiographic parameters; (ii) differences in rate of progression of three predominant genotypes; and (iii) the ability of changes in echocardiographic parameters to predict prognosis.
To assess the application of the Conners' Teacher Rating Scale (CTRS-28) in the United Kingdom, we obtained ratings from the teachers of a representative sample of 2,632 twin school children, aged between 6 and 11 years. In the older age group (ages 9-11), there were no significant differences between the present means for the CTRS-28 dimensions and the means for the original standardization sample (Goyette, Conners, & Ulrich, 1978). In the younger age group (ages 6-8), boys obtained higher average ratings on the Conduct Problem dimension and girls obtained higher average ratings on the Hyperactivity dimension, compared to the original study. Two standard deviation cutoff points, which can be used to specify "extreme" groups, identified similar numbers of children in the older age group, whether the cutoff points were based on the present or the original data. For the younger children, the present cutoff points identified consistently fewer children than the original cutoff points. Boys obtained higher scores than girls on each dimension, and there was a decrease in the mean scores with age for the Hyperactivity and Inattentive-Passive, but not Conduct Problem, dimensions. The findings highlight the need to consider the generalizability of rating scale norms and restandardization in different populations and historical time points.
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.
Background Normal mean pulmonary artery pressure (mPAP) does not exceed 20 mmHg and normal pulmonary vascular resistance (PVR) does not exceed 2 Wood Units (WU). The thresholds used to define pre-capillary pulmonary hypertension (PH) – mPAP ≥25 mmHg and PVR >3 WU – are being evaluated. It is unclear if treatment would benefit patients with mildly elevated mPAP (≥21–<25 mmHg). Purpose The EVIDENCE-PAH study aims to describe mortality and hospitalisation outcomes, clinical characteristics, therapies, and quality of life during long-term follow-up of a national cohort of patients with different levels of mPAP and PVR. We report preliminary analyses focusing on mortality and its cause in patients stratified by their baseline (BL) mPAP. Methods This retrospective analysis included PAH-treatment-naïve patients with suspected PH who received a first right heart catheterisation (RHC) between 2009 and 2017 at any of the 7 UK tertiary PH centres, which assess all PH patients in the UK. A sample of patients with BL mPAP ≥25 mmHg (stratified by PVR and treatable versus non-treatable PH) was used as a control in this analysis. Baseline characteristics, mortality and cause of mortality were stratified by mPAP (<21, ≥21–<25, ≥25 mmHg) at BL (first RHC). Mortality was also stratified by BL PVR (<1, 1–<2, 2–<3, 3–<6, ≥6 WU). Mortality analysis was done without matching cohorts. Mortality data were obtained from the Office for National Statistics, NHS Digital. Results In total, 2926 patients were analysed (968, 689 and 1269 with mPAP <21, ≥21–<25, ≥25 mmHg, respectively). Mean observation was 6.1 years. BL characteristics are in Table. Survival worsened with increasing mPAP (p<0.0001) and increasing PVR (p<0.01) (Figure). After 5 years of follow-up, 187 (27.1%) patients with mPAP ≥21–<25 mmHg had died, compared with 162 (16.7%) and 595 (46.9%) patients in the lower and higher mPAP groups, respectively. In patients with mPAP ≥21–<25 mmHg, the most common main cause of death was respiratory disease (36.4%) – with scleroderma lung disease and interstitial lung disease accounting for 69.1% of these deaths – followed by cardiac disease (16.6%) and malignancy (15.0%) (Table). PH was the main cause of death for only 1.6% of patients with mildly elevated mPAP and it was a contributor to death in 6.8% (BL mPAP <21 mmHg), 10.2% (≥21–<25 mmHg), and 40.2% (≥25 mmHg) of cases. Conclusion Long-term survival in patients with mPAP ≥21–<25 mmHg was worse than in those with normal mPAP, and better than in those with the current definition of PH. While the main cause of death was mostly unrelated to PH and further analysis is needed to understand the impact of underlying disease, mildly elevated mPAP appears to confer a worse prognosis and should be closely monitored. These data show the relevant disease burden in patients with mPAP ≥21–<25 mmHg and the need to understand if they could benefit from treatment. PVR may be key in determining patients who might benefit. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Actelion Pharmaceuticals Ltd., a Janssen pharmaceutical company of Johnson & Johnson.
Background The presence and severity of cardiac involvement in AL amyloidosis is the main driver of prognosis [1]; patients with symptomatic heart failure frequently die within 6 months [1] but median survival has nearly doubled over the past decade, mainly due to significant improvements in chemotherapy. The haematological response to chemotherapy is principally evaluated with serial measurements of serum-free light-chains (FLC) [2]. The cardiac response to chemotherapy is assessed through changes in serum concentrations of brain natriuretic peptides (including NT-proBNP) and echocardiographic parameters [3–5]. Neither are able to directly measure cardiac amyloid burden. Cardiovascular magnetic resonance (CMR) with extra-cellular volume (ECV) mapping can measure the extent cardiac amyloid infiltration [6]. Aims We investigated the ability of CMR to: 1) measure changes in response to chemotherapy; 2) assess the correlation between haematological response (HMR) and changes in cardiac amyloid; 3) assess the association between changes in cardiac amyloid and prognosis over and above existing predictors. Methods In total, 176 patients with cardiac light-chain amyloidosis treated with chemotherapy were assessed with FLC, NT-proBNP and CMR with ECV mapping at baseline (before chemotherapy), 6-months, 12-months & 24-months after commencing chemotherapy. Haematological response was categorized by reductions in FLC as: complete response (CR), very good partial response (VGPR), partial response (PR) or no response (NR). CMR response was categorized by changes in ECV as: progression (≥0.05 increase), stable (<0.05 change) or regression (≥0.05 decrease). Results A progressive increase in patients achieving either CR or VGPR was observed at each time point (61% of patients at 6-months, 71% at 12-months and 80% at 24-months). At 6-months, CMR regression was observed in 3% (all had either CR or VGPR) and progression in 32% (61% had either PR or NR; 39% had either CR or VGPR). At 1-year, CMR regression was observed in 22% (all had either CR or VGPR); progression in 22% (63% had either PR or NR; 37% had either CR or VGPR). At 2-years, CMR regression was observed in 38% (all had CR/VGPR); progression in 14% (80% had either PR or NR; 20% had either CR or VGPR). During follow-up (40±15 months), 36 (25%) patients died. CMR response at 6-months predicted death (progression HR 3.821; 95% CI 1.950–7.487; p<0.001) and remained independently associated with prognosis after adjusting for haematological response, NT-proBNP and longitudinal strain on echocardiography (p<0.01). Conclusions CMR demonstrates that cardiac amyloid deposits frequently regress following chemotherapy, but only in patients who achieve CR or VGPR, highlighting the need for deep haematological response. Changes in amyloid burden (ECV) predict outcomes after adjusting for known predictors, showing the crucial role of CMR in redefining treatment response. Funding Acknowledgement Type of funding sources: Foundation.
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