Utility of Left and Right Ventricular Strain in Arrhythmogenic Right Ventricular Cardiomyopathy: A Prospective Multicenter Registry.

BACKGROUND: Imaging evaluation of arrhythmogenic right ventricular cardiomyopathy (ARVC) remains challenging. Myocardial strain assessment by echocardiography is an increasingly utilized technique for detecting subclinical left ventricular (LV) and right ventricular (RV) dysfunction. We aimed to evaluate the diagnostic and prognostic utility of LV and RV strain in ARVC. METHODS: Patients with suspected ARVC (n = 109) from a multicenter registry were clinically phenotyped using the 2010 ARVC Revised Task Force Criteria and underwent baseline strain echocardiography. Diagnostic performance of LV and RV strain was evaluated using the area under the receiver operating characteristic curve analysis against the 2010 ARVC Revised Task Force Criteria, and the prognostic value was assessed using the Kaplan-Meier analysis. RESULTS: Mean age was 45.3±14.7 years, and 48% of patients were female. Estimation of RV strain was feasible in 99/109 (91%), and LV strain was feasible in 85/109 (78%) patients. ARVC prevalence by 2010 ARVC Revised Task Force Criteria is 91/109 (83%) and 83/99 (84%) in those with RV strain measurements. RV global longitudinal strain and RV free wall strain had diagnostic area under the receiver operating characteristic curve of 0.76 and 0.77, respectively (both P<0.001; difference NS). Abnormal RV global longitudinal strain phenotype (RV global longitudinal strain > -17.9%) and RV free wall strain phenotype (RV free wall strain > -21.2%) were identified in 41/69 (59%) and 56/69 (81%) of subjects, respectively, who were not identified by conventional echocardiographic criteria but still met the overall 2010 ARVC Revised Task Force Criteria for ARVC. LV global longitudinal strain did not add diagnostic value but was prognostic for composite end points of death, heart transplantation, or ventricular arrhythmia (log-rank P=0.04). CONCLUSIONS: In a prospective, multicenter registry of ARVC, RV strain assessment added diagnostic value to current echocardiographic criteria by identifying patients who are missed by current echocardiographic criteria yet still fulfill the diagnosis of ARVC. LV strain, by contrast, did not add incremental diagnostic value but was prognostic for identification of high-risk patients.

Identifying high risk clinical phenogroups of pulmonary hypertension through a clustering analysis.

INTRODUCTION: The classification and management of pulmonary hypertension (PH) is challenging due to clinical heterogeneity of patients. We sought to identify distinct multimorbid phenogroups of patients with PH that are at particularly high-risk for adverse events. METHODS: A hospital-based cohort of patients referred for right heart catheterization between 2005-2016 with PH were included. Key exclusion criteria were shock, cardiac arrest, cardiac transplant, or valvular surgery. K-prototypes was used to cluster patients into phenogroups based on 12 clinical covariates. RESULTS: Among 5208 patients with mean age 64±12 years, 39% women, we identified 5 distinct multimorbid PH phenogroups with similar hemodynamic measures yet differing clinical outcomes: (1) "young men with obesity", (2) "women with hypertension", (3) "men with overweight", (4) "men with cardiometabolic and cardiovascular disease", and (5) "men with structural heart disease and atrial fibrillation." Over a median follow-up of 6.3 years, we observed 2182 deaths and 2002 major cardiovascular events (MACE). In age- and sex-adjusted analyses, phenogroups 4 and 5 had higher risk of MACE (HR 1.68, 95% CI 1.41-2.00 and HR 1.52, 95% CI 1.24-1.87, respectively, compared to the lowest risk phenogroup 1). Phenogroup 4 had the highest risk of mortality (HR 1.26, 95% CI 1.04-1.52, relative to phenogroup 1). CONCLUSIONS: Cluster-based analyses identify patients with PH and specific comorbid cardiometabolic and cardiovascular disease burden that are at highest risk for adverse clinical outcomes. Interestingly, cardiopulmonary hemodynamics were similar across phenogroups, highlighting the importance of multimorbidity on clinical trajectory. Further studies are needed to better understand comorbid heterogeneity among patients with PH.

Impact of Complete Revascularization in the ISCHEMIA Trial.

BACKGROUND: Anatomic complete revascularization (ACR) and functional complete revascularization (FCR) have been associated with reduced death and myocardial infarction (MI) in some prior studies. The impact of complete revascularization (CR) in patients undergoing an invasive (INV) compared with a conservative (CON) management strategy has not been reported. OBJECTIVES: Among patients with chronic coronary disease without prior coronary artery bypass grafting randomized to INV vs CON management in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial, we examined the following: 1) the outcomes of ACR and FCR compared with incomplete revascularization; and 2) the potential impact of achieving CR in all INV patients compared with CON management. METHODS: ACR and FCR in the INV group were assessed at an independent core laboratory. Multivariable-adjusted outcomes of CR were examined in INV patients. Inverse probability weighted modeling was then performed to estimate the treatment effect had CR been achieved in all INV patients compared with CON management. RESULTS: ACR and FCR were achieved in 43.4% and 58.4% of 1,824 INV patients. ACR was associated with reduced 4-year rates of cardiovascular death or MI compared with incomplete revascularization. By inverse probability weighted modeling, ACR in all 2,296 INV patients compared with 2,498 CON patients was associated with a lower 4-year rate of cardiovascular death or MI (difference -3.5; 95% CI: -7.2% to 0.0%). In comparison, the event rate difference of cardiovascular death or MI for INV minus CON in the overall ISCHEMIA trial was -2.4%. Results were similar but less pronounced with FCR. CONCLUSIONS: The outcomes of an INV strategy may be improved if CR (especially ACR) is achieved. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

SerpinA3N deficiency attenuates steatosis and enhances insulin signaling in male mice.

Aberrant hepatic lipid metabolism is the major cause of non-alcoholic fatty liver disease (NAFLD) and is associated with insulin resistance and type 2 diabetes. Serine (or cysteine) peptidase inhibitor, clade A, member 3N (SerpinA3N) is highly expressed in the liver; however, its functional role in regulating NAFLD and associated metabolic disorders are not known. Male wildtype and hepatocyte Serpina3N knockout (HKO) mice were fed a control diet, methionine- and choline-deficient diet or high-fat high-sucrose diet to induce NAFLD and markers of lipid metabolism and glucose homeostasis were assessed. SerpinA3N protein was markedly induced in mice with fatty livers. Hepatic deletion of SerpinA3N attenuated steatosis which correlated with altered lipid metabolism genes, increased fatty acid oxidation activity and enhanced insulin signaling in mice with NAFLD. Additionally, SerpinA3N HKO mice had reduced epididymal white adipose tissue mass, leptin, and insulin levels, improved glucose tolerance, and enhanced insulin sensitivity which was associated with elevated insulin-like growth factor binding protein-1 (IGFBP1) and activation of the leptin receptor (LEPR)-STAT3 signaling pathway. Our findings provide a novel insight into the functional role of SerpinA3N in regulating NAFLD and glucose homeostasis.

Association Between Functional Tricuspid Regurgitation and Mortality Following Cardiac Surgery.

Background: Current guidelines recommend concomitant repair of certain non-severe cases of tricuspid regurgitation (TR) in patients undergoing cardiac surgery, but the prognostic relevance and postsurgical impact of the TR remain uncertain. Objectives: The purpose of this study was to determine the prognostic impact of functional TR in patients undergoing diverse cardiac surgeries and to examine the effect-modifying role of patient characteristics in patients in whom TR confers a greater risk of adverse outcomes. Methods: Patients undergoing coronary artery bypass, aortic, and mitral valve surgery were included. Patients with severe TR, organic tricuspid valve pathology, undergoing tricuspid valve surgery or without a recent preoperative echocardiogram were excluded. Clinical variables were extracted from the Society of Thoracic Surgeons Adult Cardiac Surgery Database. An independent cohort was used for external validation. Results: Of 2,119 patients (mean age 67.4 years; 29% females), TR severity was moderate in 185 (9%), mild in 636 (30%), trivial in 1,126 (53%), and absent in 172 (8%). There were 238 deaths during the median follow-up period of 2.6 years. After adjusting for relevant factors, moderate TR was found to be independently associated with mid-term mortality (HR: 2.58; 95% CI: 1.22-5.47) and with in-hospital mortality or major morbidity (OR: 3.18; 95% CI: 1.37-7.42). The association between TR and mortality was apparent when preoperative pulmonary artery systolic pressure was <40 mm Hg but not ≥40 mm Hg (P for interaction = 0.036). Conclusions: In this diverse cohort of contemporary cardiac surgery patients, moderate functional TR was associated with increased mortality and major morbidity, particularly in the absence of pulmonary hypertension.

Global Circumferential and Radial Strain Among Patients With Immune Checkpoint Inhibitor Myocarditis.

BACKGROUND: Global circumferential strain (GCS) and global radial strain (GRS) are reduced with cytotoxic chemotherapy. There are limited data on the effect of immune checkpoint inhibitor (ICI) myocarditis on GCS and GRS. OBJECTIVES: This study aimed to detail the role of GCS and GRS in ICI myocarditis. METHODS: In this retrospective study, GCS and GRS from 75 cases of patients with ICI myocarditis and 50 ICI-treated patients without myocarditis (controls) were compared. Pre-ICI GCS and GRS were available for 12 cases and 50 controls. Measurements were performed in a core laboratory blinded to group and time. Major adverse cardiovascular events (MACEs) were defined as a composite of cardiogenic shock, cardiac arrest, complete heart block, and cardiac death. RESULTS: Cases and controls were similar in age (66 ± 15 years vs 63 ± 12 years; P = 0.20), sex (male: 73% vs 61%; P = 0.20) and cancer type (P = 0.08). Pre-ICI GCS and GRS were also similar (GCS: 22.6% ± 3.4% vs 23.5% ± 3.8%; P = 0.14; GRS: 45.5% ± 6.2% vs 43.6% ± 8.8%; P = 0.24). Overall, 56% (n = 42) of patients with myocarditis presented with preserved left ventricular ejection fraction (LVEF). GCS and GRS were lower in myocarditis compared with on-ICI controls (GCS: 17.5% ± 4.2% vs 23.6% ± 3.0%; P < 0.001; GRS: 28.6% ± 6.7% vs 47.0% ± 7.4%; P < 0.001). Over a median follow-up of 30 days, 28 cardiovascular events occurred. A GCS (HR: 4.9 [95% CI: 1.6-15.0]; P = 0.005) and GRS (HR: 3.9 [95% CI: 1.4-10.8]; P = 0.008) below the median was associated with an increased event rate. In receiver-operating characteristic (ROC) curves, GCS (AUC: 0.80 [95% CI: 0.70-0.91]) and GRS (AUC: 0.76 [95% CI: 0.64-0.88]) showed better performance than cardiac troponin T (cTnT) (AUC: 0.70 [95% CI: 0.58-0.82]), LVEF (AUC: 0.69 [95% CI: 0.56-0.81]), and age (AUC: 0.54 [95% CI: 0.40-0.68]). Net reclassification index and integrated discrimination improvement demonstrated incremental prognostic utility of GRS over LVEF (P = 0.04) and GCS over cTnT (P = 0.002). CONCLUSIONS: GCS and GRS are lower in ICI myocarditis, and the magnitude of reduction has prognostic significance.

Impact of Vitamin D3 Versus Placebo on Cardiac Structure and Function: A Randomized Clinical Trial.

Background Vitamin D supplementation leads to regression of left ventricular (LV) hypertrophy and improves LV function in animal models. However, limited data exist from prospective human studies. We examined whether vitamin D supplementation improved cardiac structure and function in midlife/older individuals in a large randomized trial. Methods and Results The VITAL (Vitamin D and OmegA-3 Trial) was a nationwide double-blind, placebo-controlled randomized trial that tested the effects of vitamin D3 (2000 IU/d) and n-3 fatty acids (1 g/d) on cardiovascular and cancer risk in 25 871 individuals aged ≥50 years. We conducted a substudy of VITAL in which participants underwent echocardiography at baseline and 2 years. Images were interpreted by a blinded investigator at a central core laboratory. The primary end point was change in LV mass. Among 1054 Greater Boston-area participants attending in-clinic visits, we enrolled 1025 into this study. Seventy-nine percent returned for follow-up and had analyzable echocardiograms at both visits. At baseline, the median age was 64 years (interquartile range, 60-69 years), 52% were men, and 43% had hypertension. After 2 years, the change in LV mass did not significantly differ between the vitamin D and placebo arms (median +1.4 g versus +2.6 g, respectively; P=0.32). Changes in systolic and diastolic LV function also did not differ significantly between arms. There were no significant changes in cardiac structure and function between the n-3 fatty acids and placebo arms. Conclusions Among adults aged ≥50 years, neither vitamin D3 nor n-3 fatty acids supplementation had significant effects on cardiac structure and function after 2 years. Registration URL: https://clinicaltrials.gov/; Unique identifiers: NCT01169259 (VITAL) and NCT01630213 (VITAL-Echo).

Prognostic importance of the transmitral pressure gradient in mitral annular calcification with associated mitral valve dysfunction.

AIMS: The aim of this study was to define the natural history of patients with mitral annular calcification (MAC)-related mitral valve dysfunction and to assess the prognostic importance of mean transmitral pressure gradient (MG) and impact of concomitant mitral regurgitation (MR). METHODS AND RESULTS: The institutional echocardiography database was examined from 2001 to 2019 for all patients with MAC and MG ≥3 mmHg. A total of 5754 patients were stratified by MG in low (3-5 mmHg, n = 3927), mid (5-10 mmHg, n = 1476), and high (≥10 mmHg, n = 351) gradient. The mean age was 78 ± 11 years, and 67% were female. MR was none/trace in 32%, mild in 42%, moderate in 23%, and severe in 3%. Primary outcome was all-cause mortality, and outcome models were adjusted for age, sex, and MAC-related risk factors (hypertension, diabetes, coronary artery disease, chronic kidney disease). Survival at 1, 5, and 10 years was 77%, 42%, and 18% in the low-gradient group; 73%, 38%, and 17% in the mid-gradient group; and 67%, 25%, and 11% in the high-gradient group, respectively (log-rank P < 0.001 between groups). MG was independently associated with mortality (adjusted HR 1.064 per 1 mmHg increase, 95% CI 1.049-1.080). MR severity was associated with mortality at low gradients (P < 0.001) but not at higher gradients (P = 0.166 and 0.372 in the mid- and high-gradient groups, respectively). CONCLUSION: In MAC-related mitral valve dysfunction, mean transmitral gradient is associated with increased mortality after adjustment for age, sex, and MAC-related risk factors. Concomitant MR is associated with excess mortality in low-gradient ranges (3-5 mmHg) but gradually loses prognostic importance at higher gradients, indicating prognostic utility of transmitral gradient in MAC regardless of MR severity.

Left ventricle and mitral valve reverse remodeling in response to cardiac resynchronization therapy in nonischemic cardiomyopathy.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves left heart geometry and function in nonischemic cardiomyopathy (NICMP). We aimed to detail the effects of CRT on left ventricular (LV) and mitral valve (MV) remodeling using 2-dimensional transthoracic echocardiography. METHODS: Forty-five consecutive patients with NICMP who underwent CRT implantation between 2009 and 2012, and had pre-CRT and follow-up echocardiograms available, were included. Paired t test, linear and logistic regression, and Kaplan-Meier survival analyses were used for statistical assessment. RESULTS: The mean age and QRS duration were 60 years and 157 ms, respectively, and 13 (28.9%) were female. At a mean follow-up of 3 years, there were 22 (48.9%) "CRT responders" (≥15% reduction in LV end-systolic volume index [LVESVi]). Significant improvements were observed in LV ejection fraction (26.3% vs 34.3%) and LVESVi (87.7 vs 71.1 mL/m2 ), as well as mitral regurgitation vena contracta width, MV tenting height and area, and end-systolic interpapillary muscle distance. Five-year actuarial survival was 87.5%. Multivariate regression analyses revealed the pre-CRT LVESVi (ß = 0.52), and MV coaptation length (ß = -0.34) and septolateral annular diameter (ß = 0.25) as good correlates of follow-up LVESVi. Variables associated with CRT response were pre-CRT MV coaptation length (OR 1.75, 95% CI 1.0-3.1) and posterior leaflet tethering angle (OR 1.07, 95% CI 1.0-1.14), irrespective of baseline QRS morphology and duration (all P < .05). CONCLUSIONS: Cardiac resynchronization therapy improves LV and MV geometry and function in half of patients with NICMP, which is paralleled by decreased mitral regurgitation severity. The extent of pre-CRT LV remodeling and MV tethering are associated with CRT response.

Transvalvular Flow Rate Determines Prognostic Value of Aortic Valve Area in Aortic Stenosis.

BACKGROUND: Aortic valve area (AVA) ≤1.0 cm2 is a defining characteristic of severe aortic stenosis (AS). AVA can be underestimated at low transvalvular flow rate. Yet, the impact of flow rate on prognostic value of AVA ≤1.0 cm2 is unknown and is not incorporated into AS assessment. OBJECTIVES: This study aimed to evaluate the effect of flow rate on prognostic value of AVA in AS. METHODS: In total, 1,131 patients with moderate or severe AS and complete clinical follow-up were included as part of a longitudinal database. The effect of flow rate (ratio of stroke volume to ejection time) on prognostic value of AVA ≤1.0 cm2 for time to death was evaluated, adjusting for confounders. Sensitivity analysis was performed to identify the optimal cutoff for prognostic threshold of AVA. The findings were validated in a separate external longitudinal cohort of 939 patients. RESULTS: Flow rate had a significant effect on prognostic value of AVA. AVA ≤1.0 cm2 was not prognostic for mortality (p = 0.15) if AVA was measured at flow rates below median (≤242 ml/s). In contrast, AVA ≤1.0 cm2 was highly prognostic for mortality (p = 0.003) if AVA was measured at flow rates above median (>242 ml/s). Findings were irrespective of multivariable adjustment for age, sex, and surgical/transcatheter aortic valve replacement (as time-dependent covariates); comorbidities; medications; and echocardiographic features. AVA ≤1.0 cm2 was also not an independent predictor of mortality below median flow rate in the validation cohort. The optimal flow rate cutoff for prognostic threshold was 210 ml/s. CONCLUSIONS: Transvalvular flow rate determines prognostic value of AVA in AS. AVA measured at low flow rate is not a good prognostic marker and therefore not a good diagnostic marker for truly severe AS. Flow rate assessment should be incorporated into clinical diagnosis, classification, and prognosis of AS.

Initial Invasive or Conservative Strategy for Stable Coronary Disease.

BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).

Global Longitudinal Strain and Cardiac Events in Patients With Immune Checkpoint Inhibitor-Related Myocarditis.

BACKGROUND: There is a need for improved methods for detection and risk stratification of myocarditis associated with immune checkpoint inhibitors (ICIs). Global longitudinal strain (GLS) is a sensitive marker of cardiac toxicity among patients receiving standard chemotherapy. There are no data on the use of GLS in ICI myocarditis. OBJECTIVES: This study sought to evaluate the role of GLS and assess its association with cardiac events among patients with ICI myocarditis. METHODS: This study retrospectively compared echocardiographic GLS by speckle tracking at presentation with ICI myocarditis (cases, n = 101) to that from patients receiving an ICI who did not develop myocarditis (control subjects, n = 92). Where available, GLS was also measured pre-ICI in both groups. Major adverse cardiac events (MACE) were defined as a composite of cardiogenic shock, arrest, complete heart block, and cardiac death. RESULTS: Cases and control subjects were similar in age, sex, and cancer type. At presentation with myocarditis, 61 cases (60%) had a normal ejection fraction (EF). Pre-ICI, GLS was similar between cases and control subjects (20.3 ± 2.6% vs. 20.6 ± 2.0%; p = 0.60). There was no change in GLS among control subjects on an ICI without myocarditis (pre-ICI vs. on ICI, 20.6 ± 2.0% vs. 20.5 ± 1.9%; p = 0.41); in contrast, among cases, GLS decreased to 14.1 ± 2.8% (p < 0.001). The GLS at presentation with myocarditis was lower among cases presenting with either a reduced (12.3 ± 2.7%) or preserved EF (15.3 ± 2.0%; p < 0.001). Over a median follow-up of 162 days, 51 (51%) experienced MACE. The risk of MACE was higher with a lower GLS among patients with either a reduced or preserved EF. After adjustment for EF, each percent reduction in GLS was associated with a 1.5-fold increase in MACE among patients with a reduced EF (hazard ratio: 1.5; 95% confidence interval: 1.2 to 1.8) and a 4.4-fold increase with a preserved EF (hazard ratio: 4.4; 95% confidence interval: 2.4 to 7.8). CONCLUSIONS: GLS decreases with ICI myocarditis and, compared with control subjects, was lower among cases presenting with either a preserved or reduced EF. Lower GLS was strongly associated with MACE in ICI myocarditis presenting with either a preserved or reduced EF.

Surgery Does Not Improve Survival in Patients With Isolated Severe Tricuspid Regurgitation.

BACKGROUND: Patients with isolated tricuspid regurgitation (TR) in the absence of left-sided valvular dysfunction are often managed nonoperatively. OBJECTIVES: The purpose of this study was to assess the impact of surgery for isolated TR, comparing survival for isolated severe TR patients who underwent surgery with those who did not. METHODS: A longitudinal echocardiography database was used to perform a retrospective analysis of 3,276 adult patients with isolated severe TR from November 2001 to March 2016. All-cause mortality for patients who underwent surgery versus those who did not was analyzed in the entire cohort and in a propensity-matched sample. To assess the possibility of immortal time bias, the analysis was performed considering time from diagnosis to surgery as a time-dependent covariate. RESULTS: Of 3,276 patients with isolated severe TR, 171 (5%) underwent tricuspid valve surgery, including 143 (84%) repairs and 28 (16%) replacements. The remaining 3,105 (95%) patients were medically managed. When considering surgery as a time-dependent covariate in a propensity-matched sample, there was no difference in overall survival between patients who received medical versus surgical therapy (hazard ratio: 1.34; 95% confidence interval: 0.78 to 2.30; p = 0.288). In the subgroup that underwent surgery, there was no difference in survival between tricuspid repair versus replacement (hazard ratio: 1.53; 95% confidence interval: 0.74 to 3.17; p = 0.254). CONCLUSIONS: In patients with isolated severe TR, surgery is not associated with improved long-term survival compared to medical management alone after accounting for immortal time bias.

Catecholamine response to exercise in patients with non-obstructive hypertrophic cardiomyopathy.

KEY POINTS: Intense physical activity, a potent stimulus for sympathetic nervous system activation, is thought to increase the risk of malignant ventricular arrhythmias among patients with hypertrophic cardiomyopathy (HCM). As a result, the majority of patients with HCM deliberately reduce their habitual physical activity after diagnosis and this lifestyle change puts them at risk for sequelae of a sedentary lifestyle: weight gain, hypertension, hyperlipidaemia, insulin resistance, coronary artery disease, and increased morbidity and mortality. We show that plasma catecholamine levels remain stably low at exercise intensities below the ventilatory threshold, a parameter that can be defined during cardiopulmonary exercise testing, but rise rapidly at higher intensities of exercise. These findings suggest that cardiopulmonary exercise testing may be a useful tool to provide an individualized moderate-intensity exercise prescription for patients with HCM. ABSTRACT: Intense physical activity, a potent stimulus for sympathetic nervous system activation, is thought to increase the risk of malignant ventricular arrhythmias among patients with hypertrophic cardiomyopathy (HCM). However, the impact of exercise intensity on plasma catecholamine levels among HCM patients has not been rigorously defined. We conducted a prospective observational case-control study of men with non-obstructive HCM and age-matched controls. Laboratory-based cardiopulmonary exercise testing coupled with serial phlebotomy was used to define the relationship between exercise intensity and plasma catecholamine levels. Compared to controls (C, n = 5), HCM participants (H, n = 9) demonstrated higher left ventricular mass index (115 ± 20 vs. 90 ± 16 g/m2 , P = 0.03) and maximal left ventricular wall thickness (16 ± 1 vs. 8 ± 1 mm, P < 0.001) but similar body mass index, resting heart rate, peak oxygen consumption (H = 40 ± 13 vs. C = 42 ± 7 ml/kg/min, P = 0.81) and heart rate at the ventilatory threshold (H = 78 ± 6 vs. C = 78 ± 4% peak heart rate, P = 0.92). During incremental effort exercise in both groups, concentrations of adrenaline and noradrenaline were unchanged through low- and moderate-exercise intensity until reaching a catecholamine threshold (H = 82 ± 4 vs. C = 85 ± 3% peak heart rate, P = 0.86) after which levels of both molecules rose rapidly. In patients with mild non-obstructive HCM, plasma catecholamine levels remain stably low at exercise intensities below the ventilatory threshold but rise rapidly at higher intensities of exercise. Routine cardiopulmonary exercise testing may be a useful tool to provide an individualized moderate-intensity exercise prescription for patients with HCM.

Assessment of Tricuspid Annular Motion by Speckle Tracking in Anesthetized Patients Using Transesophageal Echocardiography.

BACKGROUND: The perioperative assessment of right ventricular (RV) function remains a challenge. Tricuspid annular plane systolic excursion (TAPSE) using M-mode is a widely used measure of RV function. However, accurate alignment of the ultrasound beam with the direction of annular movement can be difficult with transesophageal echocardiography (TEE) to measure TAPSE, precluding effective use of M-mode to measure annular excursion. Tracking of specular reflectors in the myocardium may provide an angle-independent method to assess annular motion with TEE. We hypothesized that TEE speckle tracking of the lateral tricuspid annular motion represents a comparable measurement to the well-validated M-mode TAPSE on transthoracic echocardiogram (TTE), and may be considered as a reasonable alternative to TAPSE. METHODS: This is a prospective, observational cohort study. We included all patients, who were in sinus rhythm, with a preoperative TTE within 3 months of scheduled cardiac surgery that required intraoperative TEE. Tissue motion annular displacements (TMAD) of the lateral (L), septal (S), and midpoint (M) tricuspid annulus were measured (QLAB Cardiac Motion Quantification; Philips Medical, Andover, MA) after induction of general anesthesia. This was compared to the preoperative M-mode TAPSE on TTE. RESULTS: Seventy-two consecutive patients who met eligibility requirements were enrolled from September to November 2016. Twelve were excluded due to poor image quality, allowing TMAD to be analyzed in 60 patients. TMAD was analyzed offline and TMAD analysis was able to track tricuspid annular motion in all patients. The mean TMAD (L), TMAD (S), and TMAD (M) were 17.4 ± 5.2, 10.2 ± 4.8, and 14.2 ± 4.8 mm, respectively. TMAD (L) showed close correlation with M-mode TAPSE on TTE (r = 0.87, 95% confidence interval, 0.79-0.92; P < .01). All patients with a preoperative TAPSE <17 mm had a TMAD (L) <17 mm, while 71% of those with a TAPSE ≥ 17 mm had a TMAD (L) ≥ 17 mm. There was strong positive correlation between TMAD (L) and intraoperative RV fractional area change (r = 0.86, 95% confidence interval, 0.77-0.91; P < .01). Reproducibility analysis of TMAD within and across observers showed excellent correlation. CONCLUSIONS: TMAD is a quick and angle-independent method to quantitatively assess RV longitudinal function by TEE. It correlates strongly with M-mode TAPSE on TTE. Because TMAD and TAPSE were not simultaneously measured in this study, their correlation is subject to differences in loading conditions, general anesthesia, and changes in the disease process. TMAD may be easily applied in routine clinical settings and its role in the perioperative environment deserves to be further explored.

Aortic valve replacement associated with survival in severe regurgitation and low ejection fraction.

OBJECTIVES: Although guidelines support aortic valve replacement (AVR) in patients with severe aortic regurgitation (AR) and left ventricular ejection fraction (LVEF) <50%, severe left ventricular dysfunction (LVEF <35%) is thought to confer high surgical risk. We sought to determine if a survival benefit exists with AVR compared with medical management in this high-risk, relatively rare population. METHODS: A large institutional echocardiography database was queried to identify patients with severe AR and LVEF <35%. Manual chart review was performed. Due to small sample size and population heterogeneity, corrected group prognosis method was applied, which calculates the adjusted survival curve for each individual using fitted Cox proportional hazard model. Average survival adjusted for comorbidities and age was then calculated using the weighted average of the individual survival curves. RESULTS: Initially, 2 54 614 echocardiograms were considered, representing 1 45 785 unique patients, of which 40 patients met inclusion criteria. Of those, 18 (45.0%) underwent AVR and 22 (55.0%) were managed medically. Absolute mortality was 27.8% in the AVR group and 91.2% in the medical management group. After multivariate adjustment, end-stage renal disease (HR=17.633, p=0.0335) and peripheral arterial disease (HR=6.050, p=0.0180) were associated with higher mortality. AVR was associated with lower mortality (HR=0.143, p=0.0490). Mean follow-up time of the study cohort was 6.58 years, and mean survival for patients undergoing AVR was 6.31 years. CONCLUSIONS: Even after adjustment for clinical characteristics and patient age, AVR is associated with higher survival for patients with low LVEF and severe AR. Although treatment selection bias cannot be completely eliminated by this analysis, these results provide some evidence that surgery may be associated with prolonged survival in this high-risk patient group.

Variation in the Echocardiographic Surveillance of Primary Mitral Regurgitation.

BACKGROUND: Clinical outcomes after surgical treatment of mitral regurgitation are worse if intervention occurs after deterioration of left ventricular size and function. Transthoracic echocardiographic (TTE) surveillance of patients with mitral regurgitation is indicated to avoid adverse ventricular remodeling. Overly frequent TTEs can impair patient access and reduce value in care delivery. This balance between timely surveillance and overutilization of TTE in valvular disease provides a model to study variation in the delivery of healthcare services. We investigated patient and provider factors contributing to variation in TTE utilization and hypothesized that variation was attributable to provider practice even after adjustment for patient characteristics. METHODS AND RESULTS: We obtained records of all TTEs from 2001 to 2016 completed at a large echocardiography laboratory. The outcome variable was time interval between TTEs. We constructed a mixed-effects linear regression model with the individual physician as the random effect in the model and used intraclass correlation coefficient to assess the proportion of outcome variation because of provider practice. Our study cohort was 55 773 TTEs corresponding to 37 843 intervals ordered by 635 providers. The mean interval between TTEs was 12.4 months, 17.0 months, 18.3 months, and 17.4 months for severe, moderate, mild, and trace mitral regurgitation, respectively, with 20% of providers deemed overutilizers of TTEs and 25% underutilizers. CONCLUSIONS: We conclude that there is substantial variation in follow-up intervals for TTE assessment of mitral regurgitation, despite risk-adjustment for patient variables, likely because of provider factors.

Safety of coronary CT angiography and functional testing for stable chest pain in the PROMISE trial: A randomized comparison of test complications, incidental findings, and radiation dose.

BACKGROUND: Coronary computed tomography angiography (CTA) and functional testing strategies for stable chest pain yield similar outcomes; one aspect that may guide test choice is safety. METHODS: We compared test safety (test complications, incidental findings, and effective radiation dose) between CTA and functional testing as-tested in PROMISE (PROspective Multicenter Imaging Study for Evaluation of Chest Pain). In the subgroup whose physicians intended nuclear stress over other functional tests if randomized to the functional arm, we compared radiation dose of CTA versus nuclear stress and identified characteristics associated with dose. RESULTS: Of 9470 patients, none had major and <1% had minor complications (CTA: 0.8% [37/4633] vs. functional: 0.6% [27/4837]). CTA identified more incidental findings (11.6% [539/4633] vs. 0.7% [34/4837], p < 0.001), most commonly pulmonary nodules (9.4%, 437/4633). CTA had similar 90-day cumulative radiation dose to functional testing. However, in the subgroup whose physicians intended nuclear stress (CTA 3147; nuclear 3203), CTA had lower median index test (8.8 vs. 12.6 mSv, p < 0.001) and 90-day cumulative (11.6 vs. 13.1 mSv, p < 0.001) dose, independent of patient characteristics. The lowest nuclear doses employed 1-day Tc-99m protocols (12.2 mSv). The lowest CTA doses were at sites performing ≥500 CTAs/year (6.9 mSv) and with advanced (latest available) CT scanners (5.5 mSv). CONCLUSION: Complications were negligibly rare for both CTA and functional testing. CTA detects more incidental findings. Compared to nuclear stress testing, CTA's lower radiation dose, independent of patient characteristics, makes it an attractive test choice. Radiation dose varies with imaging protocol, indicating opportunities to further reduce dose. (ClinicalTrials.gov number, NCT01174550).

Surgical Versus Medical Therapy for Prosthetic Valve Endocarditis: A Meta-Analysis of 32 Studies.

Prosthetic valve endocarditis (PVE) is associated with significant morbidity, and the optimal treatment strategy has not been clearly defined. A systematic review and meta-analysis of 32 studies comparing valve reoperation and medical therapy was performed; it included 2,636 patients, with a mean follow-up of 22 months. A valve reoperation was associated with a lower risk of 30-day mortality, greater survival at follow-up, and a similar rate of PVE recurrence. Prospective studies are warranted to confirm these findings and to clarify clinical decision-making regarding the timing and necessity of a valve reoperation, as opposed to treatment with medical therapy alone.