Schaff, Hartzell V.

Abstract Background: Aortic stenosis (AS) causes left ventricular (LV) pressure overload, leading to adverse LV remodeling and dysfunction. Identifying early subclinical markers of LV dysfunction in patients with significant AS is critical as this could provide support for earlier intervention, which may result in improved long-term outcomes. We therefore examined the impact of severe AS and its consequent increase in LV afterload on myocardial deformation and rotational mechanics by 2-dimensional (2D) and 3-dimensional (3D) speckle-tracking echocardiography. Methods: We prospectively measured various strain parameters in 168 patients (42% female, mean age 72±12 years) with severe AS and LV ejection fraction (EF) ≥50%, and compared them to normal values found in literature. 2D and 3D images were analyzed for global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), basal rotation, apical rotation, and peak systolic twist. We further assessed the degree of concordance between 2D and 3D strain, and examined their association with measures of LV preload and afterload. Results: Patients with severe AS exhibited significantly lower GLS and GRS but higher GCS, apical rotation, and twist by 2D and 3D echocardiography compared with published normal values (P=0.003 for 3D twist,P<0.001 for all others). Agreement between 2D- and 3D-GLS by concordance correlation coefficient was 0.49 (95% confidence interval: 0.39-0.57). GLS was correlated with valvulo-arterial impedance, a measure of LV afterload (r=0.34, p<0.001 and r=0.23, p=0.003, respectively). Conclusion: Patients with severe AS demonstrated lower-than-normal GLS and GRS but appear to compensate with higher-than-normal GCS, apical rotation, and twist in order to maintain a preserved LVEF. GLS showed a modest correlation with valvulo-arterial impedance.

Abstract Background: Aortic stenosis (AS) causes left ventricular (LV) pressure overload, leading to adverse LV remodeling and dysfunction. We examined the impact of severe AS and its consequent increase in LV afterload on myocardial deformation and rotational mechanics by 2-dimensional (2D) and 3-dimensional (3D) speckle-tracking echocardiography. Methods: We prospectively measured various strain parameters in 168 patients (42% female, mean age 72±12 years) with severe AS and LV ejection fraction (EF) ≥50%, and compared them to normal values found in literature. 2D and 3D images were analyzed for global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), basal rotation, apical rotation, and peak systolic twist. We further assessed the degree of concordance between 2D and 3D strain, and examined their association with measures of LV preload and afterload. Results: Patients with severe AS exhibited significantly lower GLS and GRS but higher GCS, apical rotation, and twist by 2D and 3D echocardiography compared with published normal values (P=0.003 for 3D twist,P<0.001 for all others). There was modest agreement between 2D and 3D GLS measurements (concordance correlation coefficient 0.49, 95% confidence interval 0.39-0.57). GLS was modestly correlated with valvulo-arterial impedance, a measure of LV afterload (r=0.34, p<0.001 for 2D and r=0.23, p=0.003 for 3D). Conclusion: Patients with severe AS demonstrate lower-than-normal GLS and GRS as a result of increased afterload but appear to compensate with higher-than-normal GCS, apical rotation, and twist in order to maintain a preserved LVEF. Our study provides, to our knowledge, the most comprehensive analysis to date of myocardial deformation and rotational mechanics by 2D and 3D speckle-tracking echocardiography in patients with severe AS and preserved LVEF.

Abstract Background In patients with hemodynamically-significant chronic aortic valve regurgitation (AR), the prognostic significance of routinely-measured diastolic blood pressure (DBP), resting heart rate (RHR) and physical examination signs of heart failure (HF), is unknown. Purpose To investigate the association of DBP, RHR and HF signs, with all-cause mortality. Methods This retrospective cohort study included all consecutive patients with moderately-severe or severe AR within a tertiary-referral center from 2006–2017. Patients with ≥moderate aortic stenosis and those with ≥moderate mitral stenosis/regurgitation were excluded. Results Of 820 patients (age 59±17 years; 82% men) with DBP 64±13mmHg and RHR 64±12bpm, followed for 5.5±3.5 years, 104 died under medical management and 400 underwent aortic valve surgery (AVS). In multivariable analysis, DBP (adjusted-hazard ratio [HR] 0.82 [0.68–0.98] p=0.031, per 10mmHg increase), RHR (adjusted HR 1.2 [1.01–1.41] p=0.034 per 10bpm increase), and any HF signs (adjusted HR 1.66 [1.04–2.61] p=0.032) were associated with all-cause death independently of demographics, comorbidities, and guideline-derived surgical triggers. Mortality increased in a J-curve fashion for DBP starting at 70 mmHg and peaking at 55 mmHg (Fig A,C), and in a linear fashion for RHR starting at 60bpm (Fig B, D). The association persisted after additional adjustment for medications, presence of hypertension and time-dependent AVS. A clinical score combining DBP, RHR and any HF signs increased the mortality risk-discrimination of demographics and comorbidities from 74% to 79% (p=0.01), and from 79% to 82% after addition of surgical triggers (p=0.04). Figure. Risk of death by DBP and RHR Conclusions In patients with AR, routinely-measured vital signs and physical examination are strongly associated with all-cause mortality; lower DBP, higher RHR and any HF signs are independent predictors of mortality, and provide incremental mortality risk-discriminating value to baseline demographics, comorbidities and guideline-derived surgical triggers. These findings represent a clinical paradigm shift and have guideline implications.

Systemic mastocytosis (SM) is a rare clinical condition resulting from a clonal proliferation of abnormal mast cells. The clinical presentation may vary from mild cutaneous manifestations to aggressive systemic symptoms including intermittent episodes of anaphylaxis. We present a case of a 69-year-old male with abrupt and recurrent episodes of anaphylaxis with refractory distributive shock following cardiac surgery with cardiopulmonary bypass. Following a complex postoperative course, a bone marrow biopsy ultimately confirmed the diagnosis. Although rare, SM should be considered in the differential diagnosis of postoperative patients with unexplained and recurrent episodes of distributive shock.

Abstract Background: Aortic valve stenosis (AS) commonly causes left ventricular (LV) pressure overload; thus, identifying patients with adverse remodeling/early LV dysfunction is critical. We compared 2-dimensional (2D) to 3-dimensional (3D) echocardiographic measures of LV myocardial deformation in patients with severe AS and studied the relation of LV preload and afterload (Zva) to myocardial deformation. Methods: We prospectively included 168 symptomatic patients (72±12 years) with severe AS and ejection fractions ≥50%. Strain parameters from those patients were compared with normal values found in the literature. 3D full-volume and 2D images were analyzed for global longitudinal strain (GLS), global radial strain (GRS), global circumferential strain (GCS), systolic strain rate (SRs), basal rotation (Rotmax-B), apical rotation (Rotmax-A), and peak systolic twist (Twistmax). Results: 2D–GLS and 2D–GCS decreased significantly compared with normal values (P˂.001 and P=.02, respectively); 2D Rotmax-B and Twistmax increased (P˂.001 vs normal values). Agreement between 2D–GLS and 3D–GLS by concordance correlation coefficient was 0.49 (95% CI, 0.39-0.57) in patients with AS. Both 2D– and 3D–GLS correlated with valvulo-arterial impedance (Zva) (r=0.34, P<.001; and r=0.23, P=.003, respectively). Conclusion: In patients with severe AS, GLS and GCS decreased, and basal rotation and twist increased to maintain LV ejection fraction. 2D– and 3D–GLS had a relatively fair agreement. Both 2D– and 3D–GLS correlated modestly with Zva.

Abstract OBJECTIVES Paragangliomas have unique features in the mediastinum, in part due to their location. Because of their paucity, they have not been thoroughly investigated. We studied the clinical, pathological, immunohistochemical and molecular features of mediastinal paragangliomas. METHODS Immunohistochemistry, next-generation sequencing mutation panel and the Oncoscan assay were performed. RESULTS Twenty-four patients with mediastinal paraganglioma (7 men, 29.2%) had a median age of 45.5 years (19.8–72.2). Twenty-one (87.5%) paragangliomas were completely resected. Six (of 24, 25.0%) tumours were considered metastatic. Mitotic activity occurred in 11 (of 24, 45.8%) paragangliomas. Programmed death-ligand 1 (PD-L1) (n = 23) was expressed in 6 (26%) patients in 10% (n = 2) and 1% (n = 4) of tumour cells, respectively. SDHB expression was lost in 19 (of 22, 86.4%) cases. ATRX expression was lost in 11 (of 23, 47.8%) cases. Next-generation sequencing revealed a single pathogenic mutation in 10 (of 19) specimens including SDHB (n = 4), SDHD (n = 6), SDHC (n = 1), ATRX (n = 1), and ≥2 mutations in 2 cases [SDHC and TERT (n = 1); SDHB, ATRX and TP53 (n = 1)]. Germline mutation analysis revealed the same succinate dehydrogenase mutation (or lack thereof) as identified in the paraganglioma in 11 (of 12) cases. During a median follow-up (n = 21) of 4.8 years (0.8–14.9), 3 patients developed metastases; 4 patients died, at least 1 of disease. CONCLUSIONS Mediastinal paragangliomas can be associated with morbidity and mortality. Many mediastinal paragangliomas have been reported to be associated with syndromes such as multiple endocrine neoplasia, von Hippel-Lindau or succinate dehydrogenase syndrome with mutation profiles dominated by alterations in genes associated with these syndromes.

Abstract OBJECTIVES Limited literature is available on the best management strategy for tricuspid valve (TV) disease in adults. We sought to review our long-term outcomes of TV surgery with regard to survival and reoperation. METHODS A retrospective analysis of all patients ≥18 years of age [n = 2541, aged 67 ± 13years, 1433 (56%) females] who underwent first-time TV surgery between January 1993 and December 2013 was done. There were 1735 patients who received TV repair and 806 patients underwent replacement. A gradient boosting machine model was used to derive a propensity score for predicting replacement using 27 preoperative characteristics. Four hundred and eighteen propensity-matched pairs of TV repair and replacement were identified. Cox proportional hazard regression was used on the matched subset to determine the effect of replacement. RESULTS Functional TV regurgitation was present in 54% (n = 1369). A bioprosthesis was used in 84% (n = 680) of replacements, while 54% (n = 934) of TV repairs were ring annuloplasties. Operative mortality was 8% (n = 212). Overall survival was 54%, 29% and 13% at 5, 10 and 15 years, respectively. After propensity score matching, replacement was significantly associated with increased mortality [hazard ratio (HR) 1.54, 95% confidence interval (CI) 1.18–2.00; P = 0.001]. The cumulative incidence of TV reoperation was similar between the 2 groups when accounting for the competing risk of death [Fine–Gray HR 1.56, 95% CI 0.9–2.8; P = 0.144]. CONCLUSIONS TV surgery is associated with poor outcomes due to multiple patient comorbidities. TV repair results in better survival compared to replacement in patients with similar comorbidities with no increased risk of getting a reoperation.