Native myocardial T1 and right ventricular size by CMR predict outcome in systemic sclerosis-associated pulmonary hypertension.

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.

Predictors of outcomes in mild pulmonary hypertension according to 2022 ESC/ERS Guidelines: the EVIDENCE-PAH UK study.

BACKGROUND AND AIMS: Interventional studies in pulmonary arterial hypertension completed to date have shown to be effective in symptomatic patients with significantly elevated mean pulmonary artery pressure (mPAP) (≥25 mmHg) and pulmonary vascular resistance (PVR) > 3 Wood Unit (WU). However, in health the mPAP does not exceed 20 mmHg and PVR is 2 WU or lower, at rest. The ESC/ERS guidelines have recently been updated to reflect this. There is limited published data on the nature of these newly defined populations (mPAP 21-24 mmHg and PVR >2-≤3 WU) and the role of comorbidity in determining their natural history. With the change in guidelines, there is a need to understand this population and the impact of the ESC/ERS guidelines in greater detail. METHODS: A retrospective nationwide evaluation of the role of pulmonary haemodynamics and comorbidity in predicting survival among patients referred to the UK pulmonary hypertension (PH) centres between 2009 and 2017. In total, 2929 patients were included in the study. Patients were stratified by mPAP (<21 mmHg, 21-24 mmHg, and ≥25 mmHg) and PVR (≤2 WU, > 2-≤3 WU, and >3 WU), with 968 (33.0%) in the mPAP <21 mmHg group, 689 (23.5%) in the mPAP 21-24 mmHg group, and 1272 (43.4%) in the mPAP ≥25 mmHg group. RESULTS: Survival was negatively correlated with mPAP and PVR in the population as a whole. Survival in patients with mildly elevated mPAP (21-24 mmHg) or PVR (>2-≤3WU) was lower than among those with normal pressures (mPAP <21 mmHg) and normal PVR (PVR ≤ 2WU) independent of comorbid lung and heart disease [hazard ratio (HR) 1.36, 95% confidence interval (CI) 1.14-1.61, P = .0004 for mPAP vs. HR 1.28, 95% CI 1.10-1.49, P = .0012 for PVR]. Among patients with mildly elevated mPAP, a mildly elevated PVR remained an independent predictor of survival when adjusted for comorbid lung and heart disease (HR 1.33, 95% CI 1.01-1.75, P = .042 vs. HR 1.4, 95% CI 1.06-1.86, P = .019). 68.2% of patients with a mPAP 21-24 mmHg had evidence of underlying heart or lung disease. Patients with mildly abnormal haemodynamics were not more symptomatic than patients with normal haemodynamics. Excluding patients with heart and lung disease, connective tissue disease was associated with a poorer survival among those with PH. In this subpopulation evaluating those with a mPAP of 21-24 mmHg, survival curves only diverged after 5 years. CONCLUSIONS: This study supports the change in diagnostic category of the ESC/ERS guidelines in a PH population. The newly included patients have an increased mortality independent of significant lung or heart disease. The majority of patients in this new category have underlying heart or lung disease rather than an isolated pulmonary vasculopathy. Mortality is higher if comorbidity is present. Rigorous phenotyping will be pivotal to determine which patients are at risk of progressive vasculopathic disease and in whom surveillance and recruitment to studies may be of benefit. This study provides an insight into the population defined by the new guidelines.

Cardiovascular magnetic resonance in light-chain amyloidosis to guide treatment.

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.

Prognostic utility of exercise cardiovascular magnetic resonance in patients with systemic sclerosis-associated pulmonary arterial hypertension.

AIMS: Systemic sclerosis complicated by pulmonary arterial hypertension (SSc-PAH) is a rare condition with poor prognosis. The majority of patients are categorized as intermediate risk of mortality. Cardiovascular magnetic resonance (CMR) is well placed to reproducibly assess right heart size and function, but most patients with SSc-PAH have less overtly abnormal right ventricles than other forms of PAH. The aim of this study was to assess if exercise CMR measures of cardiac size and function could better predict outcome in patients with intermediate risk SSc-PAH compared with resting CMR. METHODS AND RESULTS: Fifty patients with SSc-PAH categorized as intermediate risk underwent CMR-augmented cardiopulmonary exercise testing. Most patients had normal CMR-defined resting measures of right ventricular (RV) size and function. Nine (18%) patients died during a median follow-up period of 2.1 years (range 0.1-4.6). Peak exercise RV indexed end-systolic volume (ESVi) was the only CMR metric to predict prognosis on stepwise Cox regression analysis, with an optimal threshold < 39 mL/m2 to predict favourable outcome. Intermediate-low risk patients with peak RVESVi < 39 mL/m2 had significantly better survival than all other combinations of intermediate-low/-high risk status and peak RVESVi< or ≥39 mL/m2. In our cohort, ventilatory efficiency and resting oxygen consumption (VO2) were predictive of mortality, but not peak VO2, peak cardiac output, or peak tissue oxygen extraction. CONCLUSION: Exercise CMR assessment of RV size and function may help identify SSc-PAH patients with poorer prognosis amongst intermediate risk cohorts, even when resting CMR appears reassuring, and could offer added value to clinical PH risk stratification.

Deep phenotyping of p.(V142I)-associated variant transthyretin amyloid cardiomyopathy: Distinct from wild-type transthyretin amyloidosis?

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.

Pulmonary hypertension - the latest updates for physicians.

Pulmonary hypertension (PH) is common, with an estimated prevalence of approximately 1% that increases with age. Prompt and accurate diagnosis is key to institute timely and appropriate therapy to improve symptoms and prognosis. The international guidelines for the diagnosis and management of PH have recently been updated, with a lowering of the haemodynamic threshold for diagnosis to a mean pulmonary artery pressure >20 mmHg. New diagnostic algorithms and revised indications for screening in at-risk groups have been developed to facilitate early referral to specialist PH centres. This includes fast-track referral pathways for patients who are either clinically high-risk or are at-risk for pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH). This review summarises key changes in the PH guidelines for general physicians who are, most often, the first healthcare professionals to encounter these patients and consequently have a key role as referrers into specialist PH services.

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 < 0.001) 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.

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.

Progression of echocardiographic parameters and prognosis in transthyretin cardiac amyloidosis.

AIMS: 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. METHODS AND RESULTS: We prospectively studied 877 ATTR-CM patients attending our centre between 2000 and 2020. Serial echocardiography findings at baseline, 12 months and 24 months were compared with survival. Overall, 565 patients had wild-type ATTR-CM and 312 hereditary ATTR-CM (201 with V122I; 90 with T60A). There was progressive worsening of structural and functional parameters over time, patients with V122I ATTR-CM showing more rapid worsening of left and right ventricular structural and functional parameters compared to both wild-type and T60A ATTR-CM. Among a wide range of echocardiographic analyses, including deformation-based parameters, only worsening in the degree of mitral (MR) and tricuspid regurgitation (TR) at 12- and 24-month assessments was associated with worse prognosis (change at 12 months: MR, hazard ratio 1.43 [95% confidence interval 1.14-1.80], p = 0.002; TR, hazard ratio 1.38 [95% confidence interval 1.10-1.75], p = 0.006). Worsening in MR remained independently associated with poor prognosis after adjusting for known predictors. CONCLUSION: In ATTR-CM, echocardiographic parameters progressively worsen over time. Patients with V122I ATTR-CM demonstrate the most rapid deterioration. Worsening of MR and TR were the only parameters associated with mortality, MR remaining independent after adjusting for known predictors.

Migration of a Varicocele Coil to the Right Heart.

We describe a case of an adult patient with embolization of a varicocele coil (7 × 70 mm) to the right ventricle. We review the multimodality imaging techniques used to identify location and the importance of a multidisciplinary approach in determining management. (Level of Difficulty: Advanced.).

The Positive Predictive Value of High-Grade Squamous Intraepithelial Lesion on Cytology for the Histological Diagnosis of Cervical Intraepithelial Neoplasia 2 or Higher: A Systematic Review.

Cervical cancer is a major worldwide health problem. Therefore, regular cervical screening in order to make an early diagnosis can help to prevent cervical cancer, through identifying and treating preinvasive cervical lesions. The aim of this review is to evaluate the correlation between the cytological screening result and the final gold standard histological outcome in the diagnosis of cervical lesions. More specifically, the correlation between high-grade intraepithelial lesion (HSIL) on cytology and histological cervical intraepithelial neoplasia grade 2 or higher (CIN2+) was intended, by calculating the positive predictive value (PPV). PPV is an important value from a clinical point of view. An electronic search was carried out in the electronic databases MEDLINE (through PubMed) and the Cochrane Library (last searched beginning of December 2017), supplemented with the related article feature in PubMed and snowballing. Article selection (predefined inclusion and exclusion criteria) and data extraction were evaluated by two independent reviewers (N.K. and A.V.L.). After identifying 1,146 articles, 27 articles were finally included in this systematic review, representing 28,783 cytological HSIL diagnoses in total. The PPV of HSIL was 77.5% (range: 45.4-95.2%) for the histological diagnosis of CIN2+ and 55.4% (range: 36.4-67.6%) for the diagnosis of CIN3+. In this systematic review, 77.5% of the HSIL-positive women eventually had a CIN2+ diagnosis. The diagnostic value of a cytological HSIL result (conventional or liquid-based cytology) in the diagnosis of CIN2+ lesions is good, but a combination of tests could raise this value.

Complicated congenital splenic cyst: saved by a splenunculus.

A 12-year-old girl presented with a large congenital splenic cyst complicated by Salmonella organisms. After failure of conservative management and percutaneous drainage, a splenectomy was performed. An incidental splenunculus was preserved. On follow up the splenunculus had increased to normal splenic size and there was no evidence of Howell-Jolly bodies, suggesting normal splenic function.

Dynamic changes of edema and late gadolinium enhancement after acute myocardial infarction and their relationship to functional recovery and salvage index.

BACKGROUND: Changes in the myocardium in acute ischemia are dynamic and complex, and the characteristics of myocardial tissue on cardiovascular magnetic resonance in the acute setting are not fully defined. We investigated changes in edema and late gadolinium enhancement (LGE) with serial imaging early after acute myocardial infarction, relating these to global and segmental myocardial function at 6 months. METHODS AND RESULTS: Cardiovascular magnetic resonance scans were performed on 30 patients with ST-elevation--myocardial infarction treated by primary percutaneous coronary intervention at each of 4 time points: 12 to 48 hours; 5 to 7 days; 14 to 17 days; and 6 months. All patients showed edema at 24 hours. The mean volume of edema (% left ventricle) was 37±16 at 24 hours and 39±17 at 1 week, with a reduction to 24±13 (P<0.01) by 2 weeks. Myocardial segments with edema also had increased signal on LGE at 24 hours (κ=0.77; P<0.001). The volume of LGE decreased significantly between 24 hours and 6 months (27±15% versus 22±12%; P=0.002). Of segments showing LGE at 24 hours, 50% showed resolution by 6 months. In segments with such a reduction in LGE, 65% also showed improved wall motion (P<0.0001). The area of LGE measured at 6 months correlated more strongly with troponin at 48 hours (r=0.9; P<0.01) than LGE at 24 hours (r=0.7). The difference in LGE between 24 hours and 6 months had profound effects on the calculation of salvage index (26±21% at 24 hours versus 42±23% at 6 months; P=0.02). CONCLUSIONS: Myocardial edema is maximal and constant over the first week after myocardial infarction, providing a stable window for the retrospective evaluation of area at risk. By contrast, myocardial areas with high signal intensity in LGE images recede over time with corresponding recovery of function, indicating that acutely detected LGE does not necessarily equate with irreversible injury and may severely underestimate salvaged myocardium.