Left Atrial Deformation Imaging and Atrial Fibrillation in Patients with Rheumatic Mitral Stenosis

BackgroundAtrial fibrillation (AF) is a frequent complication of rheumatic mitral stenosis (MS) and is associated with worse outcomes. Prediction of new-onset AF by assessing left atrial (LA) mechanics with speckle-tracking echocardiography might be useful for risk stratification and guiding therapeutic strategies. Therefore, the aim of this study was to assess the association of LA reservoir strain (LASr) and strain rate (LASRr) with AF at follow-up in patients with rheumatic MS.MethodsLeft atrial reservoir strain and LASRr measured by speckle-tracking echocardiography were assessed in 125 patients (mean age, 50 ± 15 years; 80.8% female) with rheumatic MS and without a history of AF. Patients were followed up for the occurrence of a first episode of AF after the index echocardiogram.ResultsDuring a median follow-up of 32 (9.5-70) months, 41 patients (32.8%) developed new-onset AF. Patients who developed AF had significantly more impaired LASr (13.4% ± 5.2% vs 18.9% ± 8.2%; P -1 vs 0.98 ± 0.36 s-1;P -1 were independently associated with the development of AF at follow-up (hazard ratio = 7.03, 95% CI, 2.08-23.77, P = .002; and hazard ratio = 3.42, 95% CI, 1.59-7.34, P = .002, respectively).ConclusionsLASr and LASRr are impaired in patients with rheumatic MS, and the degree of impairment is associated with new-onset AF at follow-up.</p

Prognostic value of left atrial reservoir function in patients with severe primary mitral regurgitation undergoing mitral valve repair

Aims: Mitral regurgitation (MR) has a significant haemodynamic impact on the left atrium. Assessment of left atrial reservoir strain (LARS) may have important prognostic implications, incremental to left atrial (LA) volume, and conventional parameters of left ventricular (LV) structure and function. This study investigated whether preoperative assessment of LARS by speckle tracking echocardiography is associated with long-term outcomes in patients undergoing mitral valve repair for severe primary MR. Methods and results: Echocardiography was performed prior to mitral valve surgery in 566 patients (age 64 +/- 12years, 66% men) with severe primary MR. The study population was subdivided based on a LARS value of 22%, using a spline curve analysis. The primary endpoint was all-cause mortality. During a median follow-up of 7 (4-12) years, 129 (22.8%) patients died. Patients with LARS 22% (2%, 3% and 5%, respectively, P Conclusion: Preoperative LARS is independently associated with all-cause mortality in patients undergoing mitral valve repair for primary MR and provides incremental prognostic value over LA volume. LARS might be helpful to guide timing of mitral valve surgery in patients with severe primary MR.</p

Incremental value of left ventricular global longitudinal strain in moderate aortic stenosis and reduced left ventricular ejection fraction

BACKGROUNDModerate aortic stenosis (AS) often coexists with left ventricular (LV) systolic dysfunction and may affect survival through afterload mismatch. Because outcomes are ultimately driven by the condition of the LV, accurate assessment of LV performance is crucial to improve risk stratification. This study investigated the prognostic value of LV global longitudinal strain (GLS) in patients with moderate AS and reduced LV systolic dysfunction.METHODSPatients with moderate AS (aortic valve area 1.0-1.5 cm2) and reduced LV ejection fraction (EF) (RESULTSA total of 166 patients (mean age 73 ± 11 years, 71% male) were included. The cumulative 1- and 5-year mortality rates were higher in patients with LVGLS CONCLUSIONThe combination of moderate AS and reduced LV systolic dysfunction is associated with a high mortality risk. LVGLS, but not LVEF, is independently associated with mortality and provides incremental prognostic value over established risk factors in patients with moderate AS and reduced LVEF.</p

Noninvasive Left Ventricular Myocardial Work in Patients with Chronic Aortic Regurgitation and Preserved Left Ventricular Ejection Fraction

BackgroundLeft ventricular (LV) global longitudinal strain (GLS) has been proposed as a sensitive marker of myocardial damage in patients with chronic severe aortic regurgitation (AR) and preserved LV ejection fraction (LVEF). However, LV GLS does not take into account the afterload. Noninvasive LV myocardial work is a novel parameter of LV myocardial performance, which integrates measurements of myocardial deformation and noninvasive blood pressure (afterload). The aims of this study were (1) to assess noninvasive LV myocardial work in patients with chronic AR and preserved LVEF and its correlation with other echocardiographic parameters, (2) to evaluate changes of LV myocardial work after aortic valve replacement or repair (AVR), and (3) to assess the relationship between LV myocardial work and postoperative LV reverse remodeling.MethodsFifty-seven patients (53 ± 16 years; 67% men) with moderate or severe chronic AR and preserved LVEF treated by AVR were included. Noninvasive LV myocardial work indices were measured at baseline and postoperatively (between 2 and 12 months after surgery) and compared with previously reported normal reference ranges.ResultsBased on normal reference values, patients with chronic AR and preserved LVEF had preserved or increased values of LV global work index (GWI; 82% and 18%, respectively) and LV global constructive work (GCW; 74% and 25%, respectively) and preserved LV global work efficiency (GWE). Left ventricular GWI and GCW showed a positive correlation with markers of AR severity and parameters of LV systolic function. Left ventricular GWI, GCW, and GWE decreased after AVR (P P = .28). The postoperative impairment of LV GWI, observed in 28% of patients, was closely associated with reduced LV reverse remodeling.ConclusionsNoninvasive myocardial work may allow better understanding of myocardial function and energetics than afterload-dependent echocardiographic parameters in chronic AR with preserved LVEF.</p

Incorporating coronary artery calcium scoring in the prediction of obstructive coronary artery disease with myocardial ischemia: a study with sequential use of coronary computed tomography angiography and positron emission tomography imaging

BackgroundAdditional strategies are needed to refine the referral for diagnostic testing of symptomatic patients with suspected coronary artery disease (CAD). We aimed to compare various models to predict hemodynamically obstructive CAD.Methods and resultsSymptomatic patients with suspected CAD who underwent coronary artery calcium scoring (CACS) and sequential coronary computed tomography angiography (CCTA) and [15O]H2O positron emission tomography (PET) myocardial perfusion imaging were analyzed. Obstructive CAD was defined as a suspected coronary artery stenosis on CCTA with myocardial ischemia on PET (absolute stress myocardial perfusion ≤ 2.4 mL/g/min in ≥ 1 segment). Three models were developed to predict obstructive CAD-induced myocardial ischemia using logistic regression analysis: (1) basic model: including age, sex and cardiac symptoms, (2) risk factor model: adding number of risk factors to the basic model, and (3) CACS model: adding CACS to the risk factor model. Model performance was evaluated using discriminatory ability with area under the receiver-operating characteristic curves (AUC). A total of 647 patients (mean age 62 ± 9 years, 45% men) underwent CACS and sequential CCTA and PET myocardial perfusion imaging. Obstructive CAD with myocardial ischemia on PET was present in 151 (23%) patients. CACS was independently associated with myocardial ischemia (P P ConclusionsAdding CACS to the model including age, sex, cardiac symptoms and number of risk factors increases the accuracy to predict obstructive CAD with myocardial ischemia on PET in symptomatic patients with suspected CAD. </p

Interaction between sex and left ventricular reverse remodeling and its association with outcomes after transcatheter aortic valve implantation

Women with severe aortic stenosis (AS) have better long-term prognosis after transcatheter aortic valve implantation (TAVI) compared to men. Whether this is caused by sex-related differences in left ventricular (LV) reverse remodeling after TAVI is unknown. Patients with severe AS who underwent transfemoral TAVI between 2007 and 2018 were selected. LV dimensions, volumes, and ejection fraction (LVEF) were assessed by transthoracic echocardiography before TAVI and at 6 and 12 months follow-up after TAVI. LV reverse remodeling was defined as the percentual LV mass index (LVMi) reduction compared to baseline. The primary outcome was all-cause mortality. A total of 459 patients (80 ± 8 years; 52% male) were included. At 6 and 12 months follow-up, both sexes showed significant reductions in LV volumes and LVMi accompanied by improvement in LVEF, without significant differences between the sexes over time. During a median follow-up of 2.8 [IQR 1.9-4.3] years, 181 (39%) patients died. Women showed better outcomes compared to men (log-rank p = 0.024). In addition, male sex was independently associated with all-cause mortality in multivariable Cox regression (HR 1.423, 95% CI 1.039-1.951, p = 0.028). No association was observed between the interaction of percentual LVMi reduction and sex with outcomes (p = 0.64). Men and women with severe AS had similar improvement in LVEF, and similar reductions in LV volumes and LVMi at 6 and 12 months after TAVI. Women showed better survival after TAVI as compared to men. The superior outcomes noted in women after TAVI are not associated with sex differences in LV reverse remodeling.[GRAPHICS].</p

Left atrial dysfunction is an independent predictor of mortality in patients with cirrhosis treated by transjugular intrahepatic portosystemic shunt

The present study aimed to investigate (1) the association between left ventricular diastolic dysfunction (LVDD), graded according to the algorithm proposed by the Cirrhotic Cardiomyopathy Consortium, and long-term survival in patients with cirrhosis undergoing transjugular intrahepatic portosystemic shunt (TIPS) and (2) the additive prognostic value of left atrial (LA) function, as assessed by LA reservoir strain, using two-dimensional speckle-tracking echocardiography (2D-STE). A total of 129 TIPS candidates (mean +/- SD, 61 +/- 12 years; 61% men) underwent a comprehensive preprocedural echocardiography. LA dysfunction was defined by LA reservoir strain <= 35%, based on a previously suggested cut-off value. The outcome was all-cause mortality after TIPS. In the current cohort, 65 (50%) patients had normal diastolic function, 26 (20%) patients had grade 1 LVDD, 21 (16%) patients had grade 2 LVDD, and 17 (13%) patients had indeterminate diastolic function. Additionally, LA dysfunction (based on LA reservoir strain <= 35%) was noted in 67 (52%) patients. After a median follow-up of 36 months (range, 12-80), 65 (50%) patients died. All-cause mortality rates increased along worse grades of LVDD (log-rank p = 0.007) and with LA dysfunction (log-rank p = 0.001). On multivariable Cox regression analysis, Model for End-Stage Liver Disease score (hazard ratio [HR],1.06; p = 0.003), hemoglobin (HR, 0.74; p = 0.022), and LA strain, expressed as a continuous variable (HR, 0.96; p = 0.005) were independently associated with all-cause mortality. Notably, the addition of LA strain to the model provided incremental prognostic value over the established prognostic variables (delta chi(2) = 8.27, p = 0.004). Conclusion: LA dysfunction assessed with 2D-STE is independently associated with all-cause mortality in patients with cirrhosis treated by TIPS

Comparative analysis of right ventricular strain in Fabry cardiomyopathy and sarcomeric hypertrophic cardiomyopathy

Aims To perform a comparative analysis of right ventricle (RV) myocardial mechanics, assessed by 2D speckle-tracking echocardiography (2D-STE), between patients with Fabry disease and patients with sarcomeric disease.Methods and results Patients with Fabry cardiomyopathy (FC) (n = 28) were compared with patients with sarcomeric hypertrophic cardiomyopathy (HCM), matched for degree of left ventricle hypertrophy (LVH) and demographic characteristics (n = 112). In addition, patients with Fabry disease and no LVH [phenotype-negative carriers of pathogenic alpha-galactosidase gene mutations (GLA LVH-)] (n = 28) were compared with age and sex-matched carriers of sarcomeric gene mutations without LVH [Phenotype-negative carriers of pathogenic sarcomeric gene mutations (Sarc LVH-)] (n = 56). Standard echocardiography and 2D-STE were performed in all participants. Despite a subtle impairment of RV global longitudinal strain (RV-GLS) was common in both groups, patients with FC showed a more prominent reduction of RV free wall longitudinal strain (RV-FWS) and lower values of difference between RV-FWS and RV-GLS (Delta RV strain), in comparison to individuals with HCM (P Conclusion Patients with FC show a specific pattern of RV myocardial mechanics, characterized by a larger impairment of RV-FWS and lower Delta RV strain in comparison to patients with HCM, which may be helpful in the differential diagnosis between these two diseases.[GRAPHICS].</p

Left Ventricular Global Longitudinal Strain in Patients with Moderate Aortic Stenosis

BackgroundModerate aortic stenosis (AS) is associated with an increased risk for adverse events. Although reduced left ventricular (LV) global longitudinal strain (GLS) is associated with worse outcomes in patients with severe AS, its prognostic value in patients with moderate AS is unknown. The aim of this study was to investigate the prognostic implications of LV GLS in patients with moderate AS.MethodsLV GLS was evaluated using speckle-tracking echocardiography in patients with moderate AS (aortic valve area 1.0-1.5 cm2) and reported as absolute (i.e., positive) values. Patients were divided into three groups: LV ejection fraction (LVEF) ResultsA total of 760 patients (mean age, 71 ± 12 years; 61% men) were analyzed. During a median follow-up period of 50 months (interquartile range, 26-94 months), 257 patients (34%) died. Patients with LVEF P P = .592). LV GLS discriminated higher risk patients even among those with LVEF ≥ 60% (P P P P ConclusionsIn patients with moderate AS, reduced LV GLS is associated with an increased risk for all-cause mortality, even if LVEF is still preserved.</p

Arginine Deprivation With Pegylated Arginine Deiminase in Patients With Argininosuccinate Synthetase 1-Deficient Malignant Pleural Mesothelioma A Randomized Clinical Trial

IMPORTANCE: Preclinical studies show that arginine deprivation is synthetically lethal in argininosuccinate synthetase 1 (ASS1)-negative cancers, including mesothelioma. The role of the arginine-lowering agent pegylated arginine deiminase (ADI-PEG20) has not been evaluated in a randomized and biomarker-driven study among patients with cancer. OBJECTIVE: To assess the clinical impact of arginine depletion in patients with ASS1-deficient malignant pleural mesothelioma. DESIGN, SETTING, AND PARTICIPANTS: A multicenter phase 2 randomized clinical trial, the Arginine Deiminase and Mesothelioma (ADAM) study, was conducted between March 2, 2011, and May 21, 2013, at 8 academic cancer centers. Immunohistochemical screening of 201 patients (2011-2013) identified 68 with advanced ASS1-deficient malignant pleural mesothelioma. INTERVENTIONS: Randomization 2:1 to arginine deprivation (ADI-PEG20, 36.8 mg/m2, weekly intramuscular) plus best supportive care (BSC) or BSC alone. MAIN OUTCOMES AND MEASURES: The primary end point was progression-free survival (PFS) assessed by modified Response Evaluation Criteria in Solid Tumors (RECIST) (target hazard ratio, 0.60). Secondary end points were overall survival (OS), tumor response rate, safety, and quality of life, analyzed by intention to treat. We measured plasma arginine and citrulline levels, anti–ADI-PEG20 antibody titer, ASS1 methylation status, and metabolic response by 18F-fluorodeoxyglucose positron-emission tomography. RESULTS: Median (range) follow-up in 68 adults (median [range] age, 66 [48-83] years; 19% female) was 38 (2.5-39) months. The PFS hazard ratio was 0.56 (95% CI, 0.33-0.96), with a median of 3.2 months in the ADI-PEG20 group vs 2.0 months in the BSC group (P = .03) (absolute risk, 18% vs 0% at 6 months). Best response at 4 months (modified RECIST) was stable disease: 12 of 23 (52%) in the ADI-PEG20 group vs 2 of 9 (22%) in the BSC group (P = .23). The OS curves crossed, so life expectancy was used: 15.7 months in the ADI-PEG20 group vs 12.1 months in the BSC group (difference of 3.6 [95% CI, −1.0 to 8.1] months; P = .13). The incidence of symptomatic adverse events of grade at least 3 was 11 of 44 (25%) in the ADI-PEG20 group vs 4 of 24 (17%) in the BSC group (P = .43), the most common being immune related, nonfebrile neutropenia, gastrointestinal events, and fatigue. Differential ASS1 gene-body methylation correlated with ASS1 immunohistochemistry, and longer arginine deprivation correlated with improved PFS. CONCLUSIONS AND RELEVANCE: In this trial, arginine deprivation with ADI-PEG20 improved PFS in patients with ASS1-deficient mesothelioma. Targeting arginine is safe and warrants further clinical investigation in arginine-dependent cancers