Myocardial Scar and Mortality in Severe Aortic Stenosis.

BACKGROUND: Aortic valve replacement (AVR) for aortic stenosis is timed primarily on the development of symptoms, but late surgery can result in irreversible myocardial dysfunction and additional risk. The aim of this study was to determine whether the presence of focal myocardial scar preoperatively was associated with long-term mortality. METHODS: In a longitudinal observational outcome study, survival analysis was performed in patients with severe aortic stenosis listed for valve intervention at 6 UK cardiothoracic centers. Patients underwent preprocedural echocardiography (for valve severity assessment) and cardiovascular magnetic resonance for ventricular volumes, function and scar quantification between January 2003 and May 2015. Myocardial scar was categorized into 3 patterns (none, infarct, or noninfarct patterns) and quantified with the full width at half-maximum method as percentage of the left ventricle. All-cause mortality and cardiovascular mortality were tracked for a minimum of 2 years. RESULTS: Six hundred seventy-four patients with severe aortic stenosis (age, 75±14 years; 63% male; aortic valve area, 0.38±0.14 cm2/m2; mean gradient, 46±18 mm Hg; left ventricular ejection fraction, 61.0±16.7%) were included. Scar was present in 51% (18% infarct pattern, 33% noninfarct). Management was surgical AVR (n=399) or transcatheter AVR (n=275). During follow-up (median, 3.6 years), 145 patients (21.5%) died (52 after surgical AVR, 93 after transcatheter AVR). In multivariable analysis, the factors independently associated with all-cause mortality were age (hazard ratio [HR], 1.50; 95% CI, 1.11-2.04; P=0.009, scaled by epochs of 10 years), Society of Thoracic Surgeons score (HR, 1.12; 95% CI, 1.03-1.22; P=0.007), and scar presence (HR, 2.39; 95% CI, 1.40-4.05; P=0.001). Scar independently predicted all-cause (26.4% versus 12.9%; P<0.001) and cardiovascular (15.0% versus 4.8%; P<0.001) mortality, regardless of intervention (transcatheter AVR, P=0.002; surgical AVR, P=0.026 [all-cause mortality]). Every 1% increase in left ventricular myocardial scar burden was associated with 11% higher all-cause mortality hazard (HR, 1.11; 95% CI, 1.05-1.17; P<0.001) and 8% higher cardiovascular mortality hazard (HR, 1.08; 95% CI, 1.01-1.17; P<0.001). CONCLUSIONS: In patients with severe aortic stenosis, late gadolinium enhancement on cardiovascular magnetic resonance was independently associated with mortality; its presence was associated with a 2-fold higher late mortality.

Isotretinoin-induced myositis.

Retinoid-induced myositis is a phenomenon recognised in multiple case reports. We report a case of isotretinoin-induced myositis in an 18-year-old male patient. This case adds to the published literature as it demonstrates (i) myositis may occur after extended periods of isotretinoin use, (ii) should be considered as a differential diagnosis even when presenting asymmetrically and (iii) can continue to progress clinically and biochemically initially following the suspension of isotretinoin before being effectively treated with corticosteroids.

Association of Myocardial Fibrosis and Stroke Volume by Cardiovascular Magnetic Resonance in Patients With Severe Aortic Stenosis With Outcome After Valve Replacement: The British Society of Cardiovascular Magnetic Resonance AS700 Study.

Importance: Low-flow severe aortic stenosis (AS) has higher mortality than severe AS with normal flow. The conventional definition of low-flow AS is an indexed stroke volume (SVi) by echocardiography less than 35 mL/m2. Cardiovascular magnetic resonance (CMR) is the reference standard for quantifying left ventricular volumes and function from which SVi by CMR can be derived. Objective: To determine the association of left ventricular SVi by CMR with myocardial remodeling and survival among patients with severe AS after valve replacement. Design, Setting, and Participants: This multicenter longitudinal cohort study was conducted between January 2003 and May 2015 across 6 UK cardiothoracic centers. Patients with severe AS listed for either surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR) were included. Patients underwent preprocedural echocardiography and CMR. Patients were stratified by echocardiography-derived aortic valve mean and/or peak gradient and SVi by CMR into 4 AS endotypes: low-flow, low-gradient AS; low-flow, high-gradient AS; normal-flow, low-gradient AS; and normal-flow, high-gradient AS. Patients were observed for a median of 3.6 years. Data were analyzed from September to November 2021. Exposures: SAVR or TAVR. Main Outcomes and Measures: All-cause and cardiovascular (CV) mortality after aortic valve intervention. Results: Of 674 included patients, 425 (63.1%) were male, and the median (IQR) age was 75 (66-80) years. The median (IQR) aortic valve area index was 0.4 (0.3-0.4) cm2/m2. Patients with low-flow AS endotypes (low gradient and high gradient) had lower left ventricular ejection fraction, mass, and wall thickness and increased all-cause and CV mortality than patients with normal-flow AS (all-cause mortality: hazard ratio [HR], 2.08; 95% CI, 1.37-3.14; P < .001; CV mortality: HR, 3.06; 95% CI, 1.79-5.25; P < .001). CV mortality was independently associated with lower SVi (HR, 1.64; 95% CI, 1.08-2.50; P = .04), age (HR, 2.54; 95% CI, 1.29-5.01; P = .001), and higher quantity of late gadolinium enhancement (HR, 2.93; 95% CI, 1.68-5.09; P < .001). CV mortality hazard increased more rapidly in those with an SVI less than 45 mL/m2. SVi by CMR was independently associated with age, atrial fibrillation, focal scar (by late gadolinium enhancement), and parameters of cardiac remodeling (left ventricular mass and left atrial volume). Conclusions and Relevance: In this cohort study, SVi by CMR was associated with CV mortality after aortic valve replacement, independent of age, focal scar, and ejection fraction. The unique capability of CMR to quantify myocardial scar, combined with other prognostically important imaging biomarkers, such as SVi by CMR, may enable comprehensive stratification of postoperative risk in patients with severe symptomatic AS.

A novel cardiovascular magnetic resonance risk score for predicting mortality following surgical aortic valve replacement.

The increasing prevalence of patients with aortic stenosis worldwide highlights a clinical need for improved and accurate prediction of clinical outcomes following surgery. We investigated patient demographic and cardiovascular magnetic resonance (CMR) characteristics to formulate a dedicated risk score estimating long-term survival following surgery. We recruited consecutive patients undergoing CMR with gadolinium administration prior to surgical aortic valve replacement from 2003 to 2016 in two UK centres. The outcome was overall mortality. A total of 250 patients were included (68 ± 12 years, male 185 (60%), with pre-operative mean aortic valve area 0.93 ± 0.32cm2, LVEF 62 ± 17%) and followed for 6.0 ± 3.3 years. Sixty-one deaths occurred, with 10-year mortality of 23.6%. Multivariable analysis showed that increasing age (HR 1.04, P = 0.005), use of antiplatelet therapy (HR 0.54, P = 0.027), presence of infarction or midwall late gadolinium enhancement (HR 1.52 and HR 2.14 respectively, combined P = 0.12), higher indexed left ventricular stroke volume (HR 0.98, P = 0.043) and higher left atrial ejection fraction (HR 0.98, P = 0.083) associated with mortality and developed a risk score with good discrimination. This is the first dedicated risk prediction score for patients with aortic stenosis undergoing surgical aortic valve replacement providing an individualised estimate for overall mortality. This model can help clinicians individualising medical and surgical care.Trial Registration ClinicalTrials.gov Identifier: NCT00930735 and ClinicalTrials.gov Identifier: NCT01755936.

Corrigendum to: A case of pseudo-pseudo Meigs' syndrome.

[This corrects the article DOI: 10.1093/omcr/omy136.][This corrects the article DOI: 10.1093/omcr/omy136.].

A case of pseudo-pseudo Meigs' syndrome.

Here we report a case of a patient with systemic lupus erythematosus presenting with pseudo-pseudo Meigs' syndrome (PPMS): a triad of pleural effusion, ascites and raised CA-125. There have only been nine other cases reported in the literature. To our knowledge, this is the first to have an oesophago-gastro-duodenoscopy and liver biopsy as part of the diagnostic work up. Its mechanism of action is not yet fully understood but PPMS is a treatable condition that is responsive to immunosuppression. It is therefore important to consider it in patients presenting like this, where alternative diagnoses, including malignancy, have been ruled out.

Sex differences in left ventricular remodelling, myocardial fibrosis and mortality after aortic valve replacement.

OBJECTIVES: To investigate sex differences in left ventricular remodelling and outcome in patients undergoing surgical or transcatheter aortic valve replacement (SAVR/TAVR). METHODS: In this multicentre, observational, outcome study with imaging core-lab analysis, patients with severe aortic stenosis (AS) listed for intervention at one of six UK centres were prospectively recruited and underwent cardiovascular magnetic resonance imaging. The primary endpoint was all-cause mortality and secondary endpoint was cardiovascular mortality. RESULTS: 674 patients (425 men, 249 women, age 75±14 years) were included: 399 SAVR, 275 TAVR. Women were older, had higher surgical risk scores and underwent TAVR more frequently (53% vs 33.6%, p<0.001). More men had bicuspid aortic valves (BAVs) (26.7% vs 14.9%, p<0.001) and demonstrated more advanced remodelling than women. During a median follow-up of 3.6 years, 145 (21.5%) patients died, with no significant sex difference in all-cause mortality (23.3% vs 20.5%, p=0.114), but higher cardiovascular mortality in women (13.7% vs 8.5%, p=0.012). There were no significant sex-related differences in outcome in the SAVR or TAVR subgroups, or after excluding those with BAV. Factors independently associated with all-cause mortality were age, left ventricular ejection fraction (LVEF), BAV (better) and myocardial fibrosis detected with late gadolinium enhancement (LGE) in men, and age, LVEF and LGE in women. Age and LGE were independently associated with cardiovascular mortality in both sexes. CONCLUSIONS: Men demonstrate more advanced remodelling in response to a similar severity of AS. The higher cardiovascular mortality observed in women following AVR is accounted for by women having less BAV and higher risk scores resulting in more TAVR. LGE is associated with a worse prognosis in both sexes.

Osteoprotegerin and Myocardial Fibrosis in Patients with Aortic Stenosis.

Left ventricular myocardial fibrosis in patients with aortic stenosis (AS) confers worse prognosis. Plasma osteoprotegerin (OPG), a cytokine from the TNF receptor family, correlates with the degree of valve calcification in AS, reflecting the activity of the tissue RANKL/RANK/OPG (receptor activator of nuclear factor κΒ ligand/RANK/osteoprotegerin) axis, and is associated with poorer outcomes in AS. Its association with myocardial fibrosis is unknown. We hypothesised that OPG levels would reflect the extent of myocardial fibrosis in AS. We included 110 consecutive patients with AS who had undergone late-gadolinium contrast enhanced cardiovascular magnetic resonance (LGE-CMR). Patients were characterised according to pattern of fibrosis (no fibrosis, midwall fibrosis, or chronic myocardial infarction fibrosis). Serum OPG was measured with ELISA and compared between groups defined by valve stenosis severity. Some 36 patients had no fibrosis, 38 had midwall fibrosis, and 36 had chronic infarction. Patients with midwall fibrosis did not have higher levels of OPG compared to those without fibrosis (6.78 vs. 5.25 pmol/L, p = 0.12). There was no difference between those with midwall or chronic myocardial infarction fibrosis (6.78 vs. 6.97 pmol/L, p = 0.27). However, OPG levels in patients with chronic myocardial infarction fibrosis were significantly higher than those without fibrosis (p = 0.005).

Lipoprotein(a) in patients with aortic stenosis: Insights from cardiovascular magnetic resonance.

BACKGROUND: Aortic stenosis is the most common age-related valvular pathology. Patients with aortic stenosis and myocardial fibrosis have worse outcome but the underlying mechanism is unclear. Lipoprotein(a) is associated with adverse cardiovascular risk and is elevated in patients with aortic stenosis. Although mechanistic pathways could link Lipoprotein(a) with myocardial fibrosis, whether the two are related has not been previously explored. In this study, we investigated whether elevated Lipoprotein(a) was associated with the presence of myocardial replacement fibrosis. METHODS: A total of 110 patients with mild, moderate and severe aortic stenosis were assessed by late gadolinium enhancement (LGE) cardiovascular magnetic resonance to identify fibrosis. Mann Whitney U tests were used to assess for evidence of an association between Lp(a) and the presence or absence of myocardial fibrosis and aortic stenosis severity and compared to controls. Univariable and multivariable linear regression analysis were undertaken to identify possible predictors of Lp(a). RESULTS: Thirty-six patients (32.7%) had no LGE enhancement, 38 (34.6%) had midwall enhancement suggestive of midwall fibrosis and 36 (32.7%) patients had subendocardial myocardial fibrosis, typical of infarction. The aortic stenosis patients had higher Lp(a) values than controls, however, there was no significant difference between the Lp(a) level in mild, moderate or severe aortic stenosis. No association was observed between midwall or infarction pattern fibrosis and Lipoprotein(a), in the mild/moderate stenosis (p = 0.91) or severe stenosis patients (p = 0.42). CONCLUSION: There is no evidence to suggest that higher Lipoprotein(a) leads to increased myocardial midwall or infarction pattern fibrosis in patients with aortic stenosis.

A case of Takotsubo cardiomyopathy after chemotherapy.

Here we present the case of a patient with diffuse large B-cell lymphoma who was admitted to hospital for an elective autologous peripheral blood stem cell transplant after cytotoxic treatment with lomustine, cytarabine, cyclophosphomide and etoposide (LACE). On the final day of chemotherapeutic treatment, she developed sudden onset dyspnoea. Electrocardiography confirmed acute antero-lateral T-wave inversion. She went onto have coronary angiography that demonstrated unobstructed coronary arteries. Left ventriculography demonstrated apical ballooning, consistent with Takotsubo (stress) cardiomyopathy. The link between chemotherapy and Takotsubo cardiomyopathy has become increasingly recognized in recent years, although causality remains to be established and the mechanism of action is not yet fully understood.

Optimization and comparison of myocardial T1 techniques at 3T in patients with aortic stenosis.

AIMS: To determine the optimal T1 mapping approach to assess myocardial fibrosis at 3T. METHODS AND RESULTS: T1 mapping was performed at 3T using the modified look-locker-inversion sequence in 20 healthy volunteers and 20 patients with aortic stenosis (AS). Pre- and post-contrast myocardial T1, the partition coefficient (λ; ΔRmyocardium/ΔRblood, where ΔR = 1/post-contrast T1 - 1/pre-contrast T1), and extracellular volume fraction [ECV; λ (1 - haematocrit)] were assessed. After establishing the optimal time point and myocardial region for analysis, we compared the reproducibility of these T1 measures and their ability to differentiate asymptomatic patients with AS from healthy volunteers. There was no segmental variation across the ventricle in any of the T1 measures evaluated. λ and ECV did not vary with time, while post-contrast T1 was relatively constant between 15 and 30 min. Thus, mid-cavity myocardium at 20 min was used for subsequent analyses. ECV displayed excellent intra-, inter-observer, and scan-rescan reproducibility [intra-class correlation coefficients (ICC) 1.00, 0.97, and 0.96, respectively], as did λ (ICC 0.99, 0.94, 0.93, respectively). Moreover, ECV and λ were both higher in patients with AS compared with controls (ECV 28.3 ± 1.7 vs. 26.0 ± 1.6%, P < 0.001; λ 0.46 ± 0.03 vs. 0.44 ± 0.03, P = 0.02), with the former offering improved differentiation. In comparison, scan-rescan reproducibilities for pre- and post-contrast myocardial T1 were only modest (ICC 0.72 and 0.56) with no differences in values observed between cases and controls (both P> 0.05). CONCLUSIONS: ECV appears to be the most promising measure of diffuse myocardial fibrosis at 3T based upon its superior reproducibility and ability to differentiate disease from health.

18F-sodium fluoride uptake is a marker of active calcification and disease progression in patients with aortic stenosis.

BACKGROUND: 18F-Sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18F-FDG) are promising novel biomarkers of disease activity in aortic stenosis. We compared 18F-NaF and 18F-FDG uptake with histological characterization of the aortic valve and assessed whether they predicted disease progression. METHODS AND RESULTS: Thirty patients with aortic stenosis underwent combined positron emission and computed tomography using 18F-NaF and 18F-FDG radiotracers. In 12 patients undergoing aortic valve replacement surgery (10 for each tracer), radiotracer uptake (mean tissue/ BACKGROUND: =0.65; P=0.04) and osteocalcin (r=0.68; P=0.03) immunohistochemistry. There was no significant correlation between 18F-FDG uptake and CD68 staining (r=-0.43; P=0.22). After 1 year, aortic valve calcification increased from 314 (193-540) to 365 (207-934) AU (P<0.01). Baseline 18F-NaF uptake correlated closely with the change in calcium score (r=0.66; P<0.01), and this improved further (r=0.75; P<0.01) when 18F-NaF uptake overlying computed tomography-defined macrocalcification was excluded. No significant correlation was noted between valvular 18F-FDG uptake and change in calcium score (r=-0.11; P=0.66). CONCLUSIONS: 18F-NaF uptake identifies active tissue calcification and predicts disease progression in patients with calcific aortic stenosis. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01358513.

Anterior shoulder instability associated with coracoid nonunion in patients with a seizure disorder.

BACKGROUND: An association between coracoid fracture and glenohumeral instability with both a seizure disorder and the subsequent development of coracoid nonunion has not previously been recognized. This is clinically important as patients with a seizure disorder and glenohumeral instability frequently require a primary osseous reconstructive procedure, such as coracoid osteotomy and transfer to the anterior glenoid rim (the Bristow-Latarjet procedure), to address glenoid osseous deficiency. We report on coracoid fracture nonunion in five patients with a seizure disorder and anterior glenohumeral instability and discuss the implications for surgical treatment. METHODS: Coracoid fracture was specifically sought on three-dimensional reconstructions of computed tomography scans in a consecutive series of 234 patients presenting to our unit with recurrent anterior instability. In addition to demographic data, we specifically sought information on any history of shoulder injury, the mechanism of injury, or previous seizure activity in these patients. In patients with a coracoid fracture or nonunion viewed to be at high risk of failure with a soft-tissue procedure, an open osseous reconstructive procedure was performed. The type of operative procedure was determined by the location of the nonunion. RESULTS: We identified six coracoid fracture nonunions in association with anterior glenohumeral instability in five patients (mean age, 26.8 years; range, twenty-four to thirty years). All patients had instability occurring in association with seizures. In the four shoulders with the anatomic location of the coracoid nonunion at its so-called elbow, a standard Bristow-Latarjet procedure was performed. In the two shoulders in which the nonunion was more distal, an Eden-Hybbinette procedure was performed. CONCLUSIONS: We recommend having a high index of suspicion of coracoid fracture when treating patients with a seizure disorder who have anterior glenohumeral instability. In these patients, preoperative computed tomographic images allow the diagnosis of a coracoid nonunion to be made prior to surgery and help to determine whether there is sufficient intact coracoid bone to allow a Bristow-Latarjet procedure to be performed.