Outcomes in Patients With Obstructive Hypertrophic Cardiomyopathy and Concomitant Aortic Stenosis Undergoing Surgical Myectomy and Aortic Valve Replacement.

Background Hypertrophic cardiomyopathy (HCM) and aortic stenosis can cause obstruction to the flow of blood out of the left ventricular outflow tract into the aorta, with obstructive HCM resulting in dynamic left ventricular outflow tract obstruction and moderate or severe aortic stenosis causing fixed obstruction caused by calcific degeneration. We sought to report the characteristics and longer-term outcomes of patients with severe obstructive HCM who also had concomitant moderate or severe aortic stenosis requiring surgical myectomy and aortic valve replacement. Methods and Results We studied 191 consecutive patients (age 67±6 years, 52% men) who underwent myectomy and aortic valve (AV) replacement (90% bioprosthesis) at our center between June 2002 and June 2018. Clinical and echo data including left ventricular outflow tract gradient and indexed AV area were recorded. The primary outcome was death. Prevalence of hypertension (63%) and hyperlipidemia (75%) were high, with a Society of Thoracic Surgeons score of 5±4, and 70% of participants had no HCM-related sudden death risk factors. Basal septal thickness and indexed AV area were 1.9±0.4 cm and 0.72±0.2 cm2/m2, respectively, while 100% of patients had dynamic left ventricular outflow tract gradient >50 mm Hg. At 6.5±4 years, 52 (27%) patients died (1.5% in-hospital deaths). One-, 2-, and 5-year survival in the current study sample was 94%, 91%, and 83%, respectively, similar to an age-sex-matched general US population. On multivariate Cox survival analysis, age (hazard ratio [HR], 1.65; 95% CI, 1.24-2.18), chronic kidney disease (HR, 1.58; 95% CI, 1.21-2.32), and right ventricular systolic pressure on preoperative echocardiography (HR, 1.28; 95% CI, 1.05-1.57) were associated with longer-term mortality, but traditional HCM risk factors did not. Conclusions In symptomatic patients with severely obstructive HCM and moderate or severe aortic stenosis undergoing a combined surgical myectomy and AV replacement at our center, the observed postoperative mortality was significantly lower than the expected mortality, and the longer-term survival was similar to a normal age-sex-matched US population.

Outcomes in Guideline-Based Class I Indication Versus Earlier Referral for Surgical Myectomy in Hypertrophic Obstructive Cardiomyopathy.

Background In patients with obstructive hypertrophic cardiomyopathy, surgical myectomy (SM) is indicated for severe symptoms. We sought to compare long-term outcomes of patients with obstructive hypertrophic cardiomyopathy where SM was based on guideline-recommended Class I indication (Functional Class or FC ≥3 or angina/exertional syncope despite maximal medical therapy) versus earlier (FC 2 and/or impaired exercise capacity on exercise echocardiography with severe obstruction). Methods and Results We studied 2268 consecutive patients (excluding <18 years, ≥ moderate aortic stenosis and subaortic membrane, 56±14 years, 55% men), who underwent SM at our center between June 2002 and March 2018. Clinical data, including left ventricular outflow tract gradient, were recorded. Death and/or appropriate internal defibrillator discharge were primary composite end points. One thousand three hundred eighteen (58%) patients met Class I indication and 950 (42%) underwent earlier surgery; 222 (10%) had a history of obstructive coronary artery disease. Basal septal thickness, and resting and maximal left ventricular outflow tract gradient were 2.0±0.3 cm, 61±44 mm Hg, and 100±31 mm Hg, respectively. At 6.2±4 years after SM, 248 (11%) had composite events (13 [0.6%] in-hospital deaths). Age (hazard ratio [HR], 1.61; 95% CI, 1.26-1.91), obstructive coronary artery disease (HR, 1.46; 95% CI, 1.06-1.91), and Class I versus earlier SM (HR, 1.61; 95% CI, 1.14-2.12) were associated with higher primary composite events (all P<0.001). Earlier surgery had better longer-term survival (similar to age-sex-matched normal population) versus surgery for Class I indication (76 [8%] versus 193 [15%], P<0.001). Conclusions In patients with obstructive hypertrophic cardiomyopathy, earlier versus surgery for Class I indication had a better long-term survival, similar to the age-sex-matched US population.

Global, Regional, and National Burden of Calcific Aortic Valve and Degenerative Mitral Valve Diseases, 1990-2017.

BACKGROUND: Nonrheumatic valvular diseases are common; however, no studies have estimated their global or national burden. As part of the Global Burden of Disease Study 2017, mortality, prevalence, and disability-adjusted life-years (DALYs) for calcific aortic valve disease (CAVD), degenerative mitral valve disease, and other nonrheumatic valvular diseases were estimated for 195 countries and territories from 1990 to 2017. METHODS: Vital registration data, epidemiologic survey data, and administrative hospital data were used to estimate disease burden using the Global Burden of Disease Study modeling framework, which ensures comparability across locations. Geospatial statistical methods were used to estimate disease for all countries, because data on nonrheumatic valvular diseases are extremely limited for some regions of the world, such as Sub-Saharan Africa and South Asia. Results accounted for estimated level of disease severity as well as the estimated availability of valve repair or replacement procedures. DALYs and other measures of health-related burden were generated for both sexes and each 5-year age group, location, and year from 1990 to 2017. RESULTS: Globally, CAVD and degenerative mitral valve disease caused 102 700 (95% uncertainty interval [UI], 82 700-107 900) and 35 700 (95% UI, 30 500-42 500) deaths, and 12.6 million (95% UI, 11.4 million-13.8 million) and 18.1 million (95% UI, 17.6 million-18.6 million) prevalent cases existed in 2017, respectively. A total of 2.5 million (95% UI, 2.3 million-2.8 million) DALYs were estimated as caused by nonrheumatic valvular diseases globally, representing 0.10% (95% UI, 0.09%-0.11%) of total lost health from all diseases in 2017. The number of DALYs increased for CAVD and degenerative mitral valve disease between 1990 and 2017 by 101% (95% UI, 79%-117%) and 35% (95% UI, 23%-47%), respectively. There is significant geographic variation in the prevalence, mortality rate, and overall burden of these diseases, with highest age-standardized DALY rates of CAVD estimated for high-income countries. CONCLUSIONS: These global and national estimates demonstrate that CAVD and degenerative mitral valve disease are important causes of disease burden among older adults. Efforts to clarify modifiable risk factors and improve access to valve interventions are necessary if progress is to be made toward reducing, and eventually eliminating, the burden of these highly treatable diseases.

Long-Term Outcomes After Aortic Valve Surgery in Patients With Asymptomatic Chronic Aortic Regurgitation and Preserved LVEF: Impact of Baseline and Follow-Up Global Longitudinal Strain.

OBJECTIVES: This study sought to determine whether baseline left ventricular global longitudinal strain (LV-GLS) and changes in left ventricular ejection fraction (LVEF) in a subgroup of subjects at post-operative follow-up added prognostic value in patients undergoing aortic valve (AV) surgery. BACKGROUND: In patients with chronic severe aortic regurgitation (AR) and preserved LVEF, sensitive markers are needed to decide timing of AV surgery. METHODS: This was an observational study in 865 patients (asymptomatic/mildly symptomatic, 52 ± 15 years of age, 79% men) with ≥3+ chronic AR and preserved LVEF of ≥50% who underwent AV surgery between 2003 and 2015. All patients had baseline echocardiography (and LV-GLS imaging), whereas 285 patients underwent post-operative echocardiography (including LV-GLS). Primary outcome was mortality. RESULTS: Only 478 patients (56%) patients had preoperative LV-GLS values better than -19%, despite a mean LVEF of 57 ± 4%. At a median 38 days, 632 patients underwent AV replacement, whereas 233 patients had AV repair. At a median follow-up of 6.95 (interquartile range [IQR]: 5.2 to 9.1) years, 105 patients (12%) died (2% in-hospital deaths). A higher proportion of patients with baseline LV-GLS grades worse than -19% died versus those whose LV-GLS score was better (15% vs. 10%; p < 0.01), and worse LV-GLS value was independently associated with higher longer-term mortality (hazard ratio: 1.62; 95% confidence interval [CI]: 1.40 to 1.86]; p < 0.001). In the 285 patients who underwent echo at 3 to 12 months post-operatively, LVEF normalized in 91% patients; however, only 88 patients (31%) had LV-GLS values better than -19%. Patients whose follow-up LV-GLS value was better than -19% had significantly better longer-term survival than those whose LV-GLS was not (5% vs. 15%, respectively; p < 0.01). An absolute worsening of 5% of LV-GLS from baseline was associated with increased mortality. CONCLUSIONS: In patients with ≥3+ chronic AR and preserved LVEF undergoing AV surgery, a baseline LV-GLS value worse than -19% was associated with reduced survival. In a subgroup of patients who returned for 3- and 12-month follow-up examinations, persistently impaired LV-GLS was associated with increased mortality.

A novel machine learning-derived radiotranscriptomic signature of perivascular fat improves cardiac risk prediction using coronary CT angiography.

BACKGROUND: Coronary inflammation induces dynamic changes in the balance between water and lipid content in perivascular adipose tissue (PVAT), as captured by perivascular Fat Attenuation Index (FAI) in standard coronary CT angiography (CCTA). However, inflammation is not the only process involved in atherogenesis and we hypothesized that additional radiomic signatures of adverse fibrotic and microvascular PVAT remodelling, may further improve cardiac risk prediction. METHODS AND RESULTS: We present a new artificial intelligence-powered method to predict cardiac risk by analysing the radiomic profile of coronary PVAT, developed and validated in patient cohorts acquired in three different studies. In Study 1, adipose tissue biopsies were obtained from 167 patients undergoing cardiac surgery, and the expression of genes representing inflammation, fibrosis and vascularity was linked with the radiomic features extracted from tissue CT images. Adipose tissue wavelet-transformed mean attenuation (captured by FAI) was the most sensitive radiomic feature in describing tissue inflammation (TNFA expression), while features of radiomic texture were related to adipose tissue fibrosis (COL1A1 expression) and vascularity (CD31 expression). In Study 2, we analysed 1391 coronary PVAT radiomic features in 101 patients who experienced major adverse cardiac events (MACE) within 5 years of having a CCTA and 101 matched controls, training and validating a machine learning (random forest) algorithm (fat radiomic profile, FRP) to discriminate cases from controls (C-statistic 0.77 [95%CI: 0.62-0.93] in the external validation set). The coronary FRP signature was then tested in 1575 consecutive eligible participants in the SCOT-HEART trial, where it significantly improved MACE prediction beyond traditional risk stratification that included risk factors, coronary calcium score, coronary stenosis, and high-risk plaque features on CCTA (Δ[C-statistic] = 0.126, P < 0.001). In Study 3, FRP was significantly higher in 44 patients presenting with acute myocardial infarction compared with 44 matched controls, but unlike FAI, remained unchanged 6 months after the index event, confirming that FRP detects persistent PVAT changes not captured by FAI. CONCLUSION: The CCTA-based radiomic profiling of coronary artery PVAT detects perivascular structural remodelling associated with coronary artery disease, beyond inflammation. A new artificial intelligence (AI)-powered imaging biomarker (FRP) leads to a striking improvement of cardiac risk prediction over and above the current state-of-the-art.

Surgical management of left ventricular outflow tract obstruction in a specialized hypertrophic obstructive cardiomyopathy center.

OBJECTIVES: This study evaluates operative approach and contemporary surgical outcomes in the management of left ventricular outflow tract obstruction by a single surgeon at a high-volume, specialized hypertrophic cardiomyopathy center. METHODS: This is a retrospective review of 1559 consecutive operations for left ventricular outflow tract obstruction from 2005 to 2015. Demographic profiles, echocardiogram-derived ventricular morphology and hemodynamics, operative data, and in-hospital outcomes were analyzed. RESULTS: Of the 1559 operations, 586 were isolated septal myectomies, 522 were myectomies with mitral valve or subvalvular apparatus intervention, 422 were myectomies with another concomitant procedure, and 29 were isolated mitral valve interventions without myectomy. Common mitral valve interventions included anterior leaflet shortening (16%), chordae tendineae resection (9.8%), papillary muscle resection (7.2%), and papillary muscle reorientation (7.5%). Ninety-two patients underwent mitral valve replacement, 42 for left ventricular outflow tract obstruction and 50 for intrinsic mitral valve pathology. Patients undergoing mitral interventions had thinner septums (18 ± 0.4 mm vs 22 ± 0.5 mm, P < .001) and less myocardium removed (6.2 ± 3.5 g vs 8.8 ± 3.8 g, P < .001) than patients without a mitral intervention. Prevalence of in-hospital permanent pacemaker insertion was 4.2% (n = 1334) for complete heart block and 1.1% (n = 464) for isolated septal myectomy with normal preoperative conduction. Overall, there were 2 postoperative ventricular septal defects (0.13%) and none for isolated myectomies. Operative mortality was 0.38%. CONCLUSIONS: Septal myectomy can be performed safely with excellent outcomes when the procedure is performed by a highly experienced surgeon in a high-volume, specialized center. A mitral valve intervention is a useful adjunct in patients with moderate hypertrophy.

Characteristics and longer-term outcomes of paravalvular leak after aortic and mitral valve surgery.

BACKGROUND: Paravalvular leak (PVL) is often seen after aortic (AV) and mitral valve (MV) surgery, either due to infection or valve dehiscence. We sought to describe predictors of longer-term outcomes in patients who developed PVL after AV and MV surgery and were considered eligible for reoperative cardiac surgery (RCS). METHODS: We studied 495 such patients (65 ± 14 years, 65% men, 47% with MV PVL) who presented at our center between January 2003 and December 2011. Patients with severe mitral/aortic stenosis, patients with less than mild PVL, and those with prohibitive risk precluding RCS were excluded. Society of Thoracic Surgeons (STS) score was calculated. Primary endpoint was mortality. RESULTS: At baseline, mean STS score and left ventricular ejection fraction were 5.8 ± 4% and 52 ± 12%, respectively. In total, 105 (21%) had infective PVL and 72% had moderate or greater PVL. At a median of 8 days, 351 (71%) patients underwent RCS to repair PVL (3% in-hospital postoperative mortality), and at 6.6 ± 4 years, 230 (47%) patients died. On multivariable Cox survival analysis, greater STS score (hazard ratio or HR 1.35), mitral versus aortic PVL (HR 1.66), infectious etiology (HR 2.05), and greater right ventricular systolic pressure (HR 1.09) were associated with greater longer-term mortality, whereas surgery (HR 0.58) was associated with improved longer-term survival (all P < .05). CONCLUSIONS: Patients who develop mild or greater PVL after AV/MV surgery have a high rate of longer-term mortality, despite excellent perioperative outcomes. Greater STS score, right ventricular systolic pressure, infectious etiology, and MV (vs AV) involvement were all independently associated with long-term mortality, whereas RCS for PVL closure was associated with improved longer-term survival.

Rate of Progression of Aortic Stenosis and its Impact on Outcomes in Patients With Radiation-Associated Cardiac Disease: A Matched Cohort Study.

OBJECTIVES: The aim of this study was to study differences in progression of aortic stenosis (AS) in patients with mediastinal radiotherapy (XRT)-associated moderate AS versus a matched cohort during the same time frame, and to ascertain need for aortic valve replacement (AVR) and longer-term survival. BACKGROUND: Rate of progression of XRT-associated moderate AS and its impact on outcomes is not well-described. METHODS: We included 81 patients (age 61 ± 13 years; 57% female) with at least XRT-associated moderate AS (aortic valve area [AVA] 1.05 ± 0.3 cm2; mean gradient 24 ± 10 mm Hg) who had ≥2 transthoracic echocardiograms (TTEs) 1 year apart and matched them in a 1:2 fashion on the basis of age, sex, and AVA with those without prior XRT. Serial aortic valve gradients and AVA were recorded. AVR and longer-term all-cause mortality during follow-up were recorded. RESULTS: A total of 100% of patients had 1, a total of 71% had 2, and 39% had 3 follow-up TTEs. Before AVR, mean AVG and AVA were not significantly different between XRT and comparison groups. At 3.6 ± 2.0 years from baseline TTE, 146 (60%) underwent AVR (16% transcatheter), with significantly more patients in the XRT group undergoing AVR (80% vs. 50%; p < 0.01), at a much shorter time (2.9 ± 1.6 years vs. 4.1 ± 2.4 years; p < 0.01). At 6.6 ± 4.0 years from the initial TTE, 49 (20%) patients died, with a significantly higher mortality in the XRT group (40% vs. 11%; p < 0.01), with prior XRT associated with increased longer-term mortality, whereas AVR was associated with improved longer-term survival. CONCLUSIONS: In patients with moderate AS, those with prior XRT have a similar rate of progression of AS versus a comparison group. A higher proportion of patients in the XRT group were referred for AVR at a shorter time from baseline TTE. Despite that, the XRT patients had significantly higher longer-term mortality, and prior exposure to XRT was associated with significantly increased longer-term mortality.

Incremental Prognostic Utility of Left Ventricular Global Longitudinal Strain in Asymptomatic Patients With Significant Chronic Aortic Regurgitation and Preserved Left Ventricular Ejection Fraction.

OBJECTIVES: This study sought to examine the prognostic utility of left ventricular (LV) global longitudinal strain (GLS) in asymptomatic patients with ≥III+ aortic regurgitation (AR), an indexed LV end-systolic dimension of <2.5 cm/m2, and preserved left ventricular ejection fraction (LVEF). BACKGROUND: Management of asymptomatic patients with severe chronic AR and preserved LVEF is challenging and is typically based on LV dimensions. METHODS: We studied 1,063 such patients (age 53 ± 16 years; 77% men) seen between 2003 and 2010 (excluding those with symptoms, obstructive coronary artery disease, acute AR/dissection, aortic/mitral stenosis, more than moderate mitral regurgitation, and previous cardiac surgery). Society of Thoracic Surgeons (STS) score was calculated. The primary endpoint was mortality. Average resting LV-GLS was measured offline on 2-, 3-, and 4-chamber views using Velocity Vector Imaging (Siemens, Malvern, Pennsylvania). RESULTS: Mean STS score, LVEF, LV-GLS, and right ventricular systolic pressure were 4.4 ± 5.0%, 57.0 ± 4.0%, -19.5 ± 0.2%, and 31.0 ± 9.0 mm Hg, respectively. In total, 671 patients (63%) underwent aortic valve surgery at a median of 42 days after the initial evaluation. At 6.8 ± 3.0 years, 146 patients (14%) had died. On multivariable Cox survival analysis, LV-GLS (hazard ratio [HR]: 1.11), STS score (HR: 1.51), indexed LV end-systolic dimension (HR: 0.50), right ventricular systolic pressure (HR: 1.33), and aortic valve surgery (HR: 0.35) were associated with longer term mortality (all p < 0.001). Sequential addition of LV-GLS and aortic valve surgery improved the C-statistic for longer term mortality for the clinical model (STS score + right ventricular systolic pressure + indexed LV end-systolic dimension) from 0.61 (95% confidence interval [CI]: 0.51 to 0.72) to 0.67 (95% CI: 0.54 to 0.87) and to 0.77 (95% CI: 0.63 to 0.90), respectively (p < 0.001 for both). A significantly higher proportion (log-rank p = 0.01) of patients with LV-GLS worse than median (-19.5%) died versus those with an LV-GLS better than median (86 of 513 [17%] vs. 60 of 550 [11%]). The risk of death at 5 years significantly increased with an LV-GLS of worse than -19%. CONCLUSIONS: In asymptomatic patients with ≥III+ chronic AR and preserved LVEF, worsening LV-GLS was associated with longer term mortality, providing incremental prognostic value and improved reclassification.

Aortic Cross-Sectional Area/Height Ratio and Outcomes in Patients With Bicuspid Aortic Valve and a Dilated Ascending Aorta.

BACKGROUND: In patients with bicuspid aortic valve and dilated proximal ascending aorta, we sought to assess (1) factors associated with increased longer-term cardiovascular mortality and (2) incremental prognostic use of indexing aortic root to patient height. METHODS AND RESULTS: We studied 969 consecutive bicuspid aortic valve patients (50±13 years; 87% men) with proximal aorta ≥4 cm, who also had a gated contrast-enhanced thoracic computed tomography or magnetic resonance angiography. A ratio of ascending aortic area/height was calculated on tomography, and ≥10 cm2/m was considered abnormal, as previously reported. Society of Thoracic Surgeons score and cardiovascular death were recorded. Greater than or equal to III+ aortic regurgitation and severe aortic stenosis were seen in 37% and 10%, respectively. Society of Thoracic Surgeons score and right ventricular systolic pressure were 2±3 and 15±16 mm Hg, respectively. Abnormal ascending aortic area/height ratio was noted in 33%; 44% underwent ascending aortic surgery at 34 days. At 10.8 years (interquartile range, 9.6-12.3), 82 (9%) died (0.4% in-hospital postoperative mortality). On multivariable Cox survival analysis, ascending aortic area/height ratio (hazard ratio, 2; 95% confidence interval, 1.20-3.35) was associated with cardiovascular death, whereas aortic surgery (hazard ratio, 0.46; confidence interval, 0.26-0.80) was associated with improved survival (both P<0.01). Of the 405 patients with ascending aortic diameter of 4.5 to 5.5 cm, 64% had an abnormal ascending aortic area/height ratio, and 70% deaths occurred in patients with an abnormal ratio. CONCLUSIONS: In bicuspid aortic valve patients with dilated proximal ascending aorta, ascending aortic area/height ratio was independently associated with cardiovascular death.

Long-Term Outcomes in Patients With Aortic Regurgitation and Preserved Left Ventricular Ejection Fraction.

BACKGROUND: Chronic severe aortic regurgitation (AR) imposes significant volume and pressure overload on the left ventricle (LV), but such patients typically remain in an asymptomatic state for a very long time. OBJECTIVES: This study sought to examine long-term outcomes in a contemporary group of patients with grade III+ chronic AR and preserved left ventricular ejection fraction (LVEF) and the value of aortic valve (AV) surgery on long-term survival. We also wanted to reassess the threshold of LV dimension, beyond which mortality significantly increases. METHODS: The authors studied 1,417 such patients (mean 54 ± 16 years of age, 75% men) seen between 2002 and 2010. Clinical data were obtained and Society of Thoracic Surgeons (STS) score was calculated. The primary endpoint was mortality. RESULTS: Mean STS score was 5.5% ± 8%, and mean LVEF was 57 ± 4%, whereas 1,228 patients (87%) were asymptomatic, and 93 patients (7%) had indexed LV end-systolic dimension (iLVESD) ≥2.5 cm/m2. At 6.6 ± 3 years, 933 patients (66%) underwent AV surgery (36% isolated AV surgery, 16% concomitant coronary bypass, and 58% aortic replacement), and 262 patients (19%) died. In-hospital postoperative mortality was 2% (0.6% in isolated AV surgery). On multivariate Cox survival analysis, compared to the group of iLVESD <2.5 cm/m2 and no AV surgery, the 2 groups of iLVESD <2.5 cm/m2 with AV surgery and iLVESD ≥2.5 cm/m2 with AV surgery were associated with improved survival (hazard ratios: 0.62 and 0.42, respectively; both p < 0.01). Survival of patients who underwent AV surgery was similar to that of an age- and sex-matched U.S. population with 96% of deaths occurring in those with iLVESD <2.5 cm/m2. CONCLUSIONS: At a high-volume experienced center, patients with grade III or greater AR and preserved LVEF demonstrated significantly improved long-term survival following AV surgery. The risk of death significantly increased at a lower LV dimension threshold than previously described.

Synergistic Utility of Brain Natriuretic Peptide and Left Ventricular Global Longitudinal Strain in Asymptomatic Patients With Significant Primary Mitral Regurgitation and Preserved Systolic Function Undergoing Mitral Valve Surgery.

BACKGROUND: In asymptomatic patients with ≥3+ mitral regurgitation and preserved left ventricular (LV) ejection fraction who underwent mitral valve surgery, we sought to discover whether baseline LV global longitudinal strain (LV-GLS) and brain natriuretic peptide provided incremental prognostic utility. METHODS AND RESULTS: Four hundred and forty-eight asymptomatic patients (61±12 years and 69% men) with ≥3+ primary mitral regurgitation and preserved left ventricular ejection fraction, who underwent mitral valve surgery (92% repair) at our center between 2005 and 2008, were studied. Baseline clinical and echocardiographic data (including LV-GLS using Velocity Vector Imaging, Siemens, PA) were recorded. The Society of Thoracic Surgeons score was calculated. The primary outcome was death. Mean Society of Thoracic Surgeons score, left ventricular ejection fraction, mitral effective regurgitant orifice, indexed LV end-diastolic volume, and right ventricular systolic pressure were 4±1%, 62±3%, 0.55±0.2 cm(2), 58±13 cc/m(2), and 37±15 mm Hg, respectively. Forty-five percent of patients had flail. Median log-transformed BNP and LV-GLS were 4.04 (absolute brain natriuretic peptide: 60 pg/dL) and -20.7%. At 7.7±2 years, death occurred in 41 patients (9%; 0% at 30 days). On Cox analysis, a higher Society of Thoracic Surgeons score (hazard ratio 1.55), higher baseline right ventricular systolic pressure (hazard ratio 1.11), more abnormal LV-GLS (hazard ratio 1.17), and higher median log-transformed BNP (hazard ratio 2.26) were associated with worse longer-term survival (all P<0.01). Addition of LV-GLS and median log-transformed BNP to a clinical model (Society of Thoracic Surgeons score and baseline right ventricular systolic pressure) provided incremental prognostic utility (χ(2) for longer-term mortality increased from 31-47 to 61; P<0.001). CONCLUSIONS: In asymptomatic patients with significant primary mitral regurgitation and preserved left ventricular ejection fraction who underwent mitral valve surgery, brain natriuretic peptide and LV-GLS provided synergistic risk stratification, independent of established factors.