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Objective: Calcium metabolism has long been implicated in aortic stenosis (AS). Studies assessing the long-term safety of oral calcium and/or vitamin D in AS are scarce yet imperative given the rising use among an elderly population prone to deficiency. We sought to identify the associations between supplemental calcium and vitamin D with mortality and progression of AS., Methods: In this retrospective longitudinal study, patients aged ≥60 years with mild-moderate native AS were selected from the Cleveland Clinic Echocardiography Database from 2008 to 2016 and followed until 2018. Groups were stratified into no supplementation, supplementation with vitamin D alone and supplementation with calcium±vitamin D. The primary outcomes were mortality (all-cause, cardiovascular (CV) and non-CV) and aortic valve replacement (AVR), and the secondary outcome was AS progression by aortic valve area and peak/mean gradients., Results: Of 2657 patients (mean age 74 years, 42% women) followed over a median duration of 69 months, 1292 (49%) did not supplement, 332 (12%) took vitamin D alone and 1033 (39%) supplemented with calcium±vitamin D. Calcium±vitamin D supplementation was associated with a significantly higher risk of all-cause mortality (absolute rate (AR)=43.0/1000 person-years; HR=1.31, 95% CI (1.07 to 1.62); p=0.009), CV mortality (AR=13.7/1000 person-years; HR=2.0, 95% CI (1.31 to 3.07); p=0.001) and AVR (AR=88.2/1000 person-years; HR=1.48, 95% CI (1.24 to 1.78); p<0.001). Any supplementation was not associated with longitudinal change in AS parameters in a linear mixed-effects model., Conclusions: Supplemental calcium with or without vitamin D is associated with lower survival and greater AVR in elderly patients with mild-moderate AS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Patients with constrictive pericarditis (CP) with active inflammation may show resolution with anti-inflammatory therapy. We aimed to investigate the impact of anti-inflammatory medications on constrictive pathophysiology using echocardiography in patients with CP., Methods: We identified 35 patients with CP who were treated with anti-inflammatory medications (colchicine, prednisone, non-steroidal anti-inflammatory drugs) after diagnosis of CP (mean age 58±13; 80% male). Clinical resolution of CP (transient CP) was defined as improvement in New York Heart Association class during follow-up. We assessed constrictive pathophysiology using regional myocardial mechanics by the ratio of peak early diastolic tissue velocity (e') at the lateral and septal mitral annulus by tissue Doppler imaging (lateral/septal e') or the ratio of the left ventricular lateral and septal wall longitudinal strain (LS lateral /LS septal ) by two-dimensional speckle-tracking echocardiography. Longitudinal data were analysed using a mixed effects model., Results: During a median follow-up of 323 days, 20 patients had transient CP, whereas 15 patients had persistent CP. Transient CP had higher baseline erythrocyte sedimentation rates (ESR) (p=0.003) compared with persistent CP. There were no significant differences in LS lateral /LS septal and lateral/septal e'. During follow-up, only transient CP showed improvement in lateral/septal e' (p<0.001) and LS lateral /LS septal (p=0.003), and recovery of inflammatory markers was similar between the two groups. In the logistic model, higher baseline ESR and greater improvement in lateral/septal e' and LS lateral /LS septal were associated with clinical resolution of CP using anti-inflammatory therapy., Conclusions: Improvement of constrictive physiology detected by lateral/septal e' and LS lateral /LS septal was associated with resolution of clinical symptoms after anti-inflammatory treatment. Serial monitoring of these markers could be used to identify transient CP., Competing Interests: Competing interests: ALK: research grant and scientific advisory board for Kiniksa; scientific advisory board for Sobi and Pfizer. PCC: scientific advisory board for Kiniksa., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Cardiac amyloidosis (CA) is a rapidly progressive disease that portends poor prognosis. Our objective was to evaluate the prognostic impact of relative regional strain ratio (RRSR, a measure of the relative apical sparing of longitudinal strain (LS)) in CA., Methods: This is a retrospective study evaluating 97 patients with CA from 2004 to 2013. Patients were included if they met criteria for CA based on endomyocardial biopsy or advanced imaging criteria coupled with either extracardiac biopsy or genetic analysis. Baseline clinical and imaging data were collected and compared between light-chain amyloidosis (AL) (n=59) and transthyretin amyloidosis (ATTR) (n=38) subtypes. RRSR was defined as the average apical LS divided by the sum of the average mid and basal LS values. A Cox proportional hazards model was used to assess the effects of clinical and echocardiographic characteristics, including RRSR, on the outcome of time to death or heart transplantation., Results: Despite younger age, the AL subtype had a statistically significant association with the composite outcome as compared with ATTR (p=0.022). Log-transformed RRSR was independently associated with the composite outcome at 5 years (HR 2.45 (1.36 to 4.40), p=0.003). Patients with low ejection fraction and high RRSR had the worst prognosis. In multivariable analysis, RRSR remained predictive of the primary outcome (p=0.018). Addition of covariates related to systolic function (global LS and ejection fraction) to the model attenuated this effect., Conclusions: High RRSR is adversely prognostic in patients with cardiac amyloid. This novel tool is both diagnostic and prognostic and may have implications in management and suitability for treatment., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: We sought to assess the impact of myocardial scar burden (MSB) on the association between implantable cardioverter defibrillator (ICD) implantation and mortality in patients with ischaemic cardiomyopathy (ICM) and left ventricular EF ≤ 40%. In addition, we sought to determine the impact of gender on survival benefit with ICD implantation., Design: Retrospective observational study., Setting: Single US tertiary care centre., Patients: Consecutive patients with significant ICM who underwent delayed hyperenhancement-MRI between 2002 and 2006., Interventions: ICD implantation., Main Outcome Measures: All-cause mortality and cardiac transplantation., Results: Follow-up of 450 consecutive patients, over a mean of 5.8 years, identified 186 deaths. Cox proportional hazard modelling was used to evaluate associations among MSB, gender and ICD with respect to all-cause death as the primary endpoint. ICDs were implanted in 163 (36%) patients. On multivariable analysis, Scar% (χ² 28.21, p<0.001), Gender (χ² 12.39, p=0.015) and ICD (χ² 9.57, p=0.022) were independent predictors of mortality after adjusting for multiple parameters. An interaction between MSB×ICD (χ² 9.47, p=0.009) demonstrated significant differential survival with ICD based on MSB severity. Additionally, Scar%×ICD×Gender (χ² 6.18, p=0.048) suggested that men with larger MSB had significant survival benefit with ICD, but men with smaller MSB derived limited benefit with ICD implantation. However, the inverse relationship was found in women., Conclusions: MSB is a powerful independent predictor of mortality in patients with and without ICD implantation. In addition, MSB may predict gender-based significant differences in survival benefit from ICDs in patients with severe ICM.

Objective: Left atrial (LA) function is an important contributor to cardiac function in a variety of disease states and especially with exercise. The purpose of this study was to assess the role of LA function in the left ventricular (LV) filling pressure (E/e') response to exercise and exercise tolerance in patients with preserved LV ejection fraction (LVEF)., Methods: LA contractile function (LA strain peak negative), conduit function (LA strain peak positive), and reservoir function (LA strain total) were measured from speckle tracking in 486 patients with preserved LVEF and negative exercise echocardiography for ischaemia. Maximal exercise tolerance was expressed as the estimated metabolic equivalents (METs). Per cent predicted METs was calculated in accordance with described nomograms. Features associated with exercise capacity were sought in a multiple linear regression, and compared using standardised β., Results: Patients with increased stress E/e' had significantly lower LA strain profiles and larger LA volume than the remainder. LA strain total was strongly associated with exercise capacity in multivariate analysis (ß=0.21, p<0.001). E/e' rest was also associated with exercise capacity (ß=-0.11, p=0.001). Other independent correlates of exercise capacity were age (ß=-0.36, p<0.001), male gender (ß=0.34, p<0.001) and body mass index (ß=-0.23, p<0.001). The best predictor of per cent predicted METs was total LA strain in multivariate analysis., Conclusions: The association of reduced LA function with impaired exercise capacity was similar to that of elevated LVE/e', emphasising the role of ventriculo-atrial coupling to cardiac dysfunction with preserved LVEF.

Background: Exercise capacity in patients with hypertrophic cardiomyopathy (HCM) varies despite similar diastolic dysfunction, left ventricular outflow tract (LVOT) obstruction and mitral regurgitation (MR). Pulse wave velocity (PWV), determined by cardiac magnetic resonance (CMR), measures aortic stiffness and is abnormal in patients with HCM in comparison with controls., Objective: To determine potential clinical and imaging predictors of peak oxygen consumption (pVO(2)) in patients with HCM., Methods: Fifty newly referred patients with HCM (62% men, 44+/-13 years, 90% receiving optimal drugs, 18% hypertensive) underwent Doppler echocardiography (transthoracic echocardiography (TTE)), cardiopulmonary exercise testing and CMR for symptom evaluation. TTE variables (diastology, post exercise MR and LVOT gradient (mmHg)), pVO(2) (ml/kg/min) and CMR variables (PWV (aortic path length between mid- and descending aorta/time delay between arrival of the foot of the pulse wave between two points, m/s), and LV volumetric indices) were measured., Results: After exercise LVOT gradient, MR, deceleration time and pVO(2) were 104+/-52, 1+/-1, 240+/-79 ms, and 25+/-6, respectively. Mean basal septal thickness (cm), PWV, EF, ESV index (ml/m(2)), EDV index (ml/m(2)) and LV mass index (g/m(2)) were 1.9+/-0.5, 9.3+/-7, 64%+/-7, 32+/-9, 87+/-17 and 112+36, respectively. Multiple regression analyses showed that only age (beta=-0.38, p=0.004) and PWV (beta=-0.33, p=0.01) predicted pVO(2)., Conclusion: In patients with HCM, age and PWV are predictors of pVO(2), independent of LV thickness, LVOT gradient and diastolic indices. Aortic stiffness potentially has a role in evaluation of symptoms of patients with HCM.

Background: Patients with hypertrophic cardiomyopathy (HCM) exhibit a difference in left ventricular outflow tract (LVOT) obstruction, independently of basal septal thickness (BST). Some patients with HCM have a steeper left ventricle to aortic root angle than controls., Objective: To test the predictors of the LV-aortic root angle and the association between LV-aortic root angle and LVOT obstruction using three-dimensional imaging., Patients: 153 consecutive patients with HCM (mean (SD) age 46 (14) years, 68% men) and 62 patients with hypertensive heart disease of the elderly (all >65 years of age, 73 (6) years, 34% men) who underwent whole-heart three-dimensional cardiac magnetic resonance (CMR) angiography (1.5 T) and Doppler echocardiography. Forty-two controls (age 43 (11) years, 38% men) who underwent contrast-enhanced multidetector computed tomography and were free of cardiovascular pathology were also studied., Main Outcomes: LV-aortic root angle, BST and maximal non-exercise LVOT gradient were measured in patients with HCM and in hypertensive-elderly patients. Additionally, LV-aortic root angle and BST were measured in controls., Results: The mean (SD) LV-aortic root angle was significantly different (p<0.001) in the three groups: HCM (134 (10) degrees ), hypertensive-elderly (128 (10) degrees ), control (140 (7) degrees ). There was an inverse correlation between age and LV-aortic root angle in the three groups (all p<0.001): HCM (r = -0.56), hypertensive-elderly (r = -0.35), control (r = -0.48). On univariate analysis, in the HCM group, LV-aortic root angle (beta = -0.34, p<0.001), age (beta = 0.23, p = 0.01) and end-systolic volume index (beta = -0.20, p = 0.02), but not BST (beta = 0.02, p = 0.8), were associated with LVOT gradient. On multivariate analysis, only LV-aortic root angle was associated with LVOT gradient., Conclusions: Patients with HCM have a steeper LV-aortic root angle than controls. In patients with HCM, a steeper LV-aortic root angle predicts dynamic LVOT obstruction, independently of BST.

Objective: To compare head to head the indices of left ventricular contractile reserve assessed by high-dose dobutamine in the five-year prognosis of patients with idiopathic dilated cardiomyopathy., Design and Setting: Prospective study in a tertiary care centre., Patients: 63 consecutive patients with idiopathic dilated cardiomyopathy., Interventions: High-dose dobutamine stress echocardiography was performed in progressive stages lasting 5 min each. Wall motion score index, ejection fraction, cardiac power output and end systolic pressure to volume ratio were evaluated as indices of left ventricular contractility., Main Outcome Measure: Five-year cardiac mortality., Results: During the follow up of 59 patients, 27 (45.8%) died of cardiac causes. According to Kaplan-Meier and receiver operating characteristic analyses all indices of contractile reserve differentiated patients with respect to cardiac death. Wall motion score index achieved the best separation (log rank 21.75, p < 0.0001, area under the curve 0.84), followed by change in ejection fraction (log rank 11.25, p = 0.0008, area under the curve 0.79), end systolic pressure to volume ratio (log rank 14.32, p = 0.0002, area under the curve 0.75) and cardiac power output (log rank 9.84, p = 0.0017, area under the curve 0.71). Cox's regression model identified wall motion score index as the only independent predictor of cardiac death., Conclusions: These data show that all examined indices of left ventricular contractile reserve are predictive of five-year prognosis, but change in wall motion score index may have the greatest prognostic potential.