Peyman Naji

Predictors of Long-Term Outcomes in Symptomatic Hypertrophic Obstructive Cardiomyopathy Patients Undergoing Surgical Relief of Left Ventricular Outflow Tract Obstruction

Background— We report the predictors of long-term outcomes of symptomatic hypertrophic cardiomyopathy patients undergoing surgical relief of left ventricular outflow tract obstruction. Methods and Results— We studied 699 consecutive patients who have hypertrophic cardiomyopathy with severe symptomatic left ventricular outflow tract obstruction (47±11 years, 63% male) intractable to maximal medical therapy, who were referred to a tertiary hospital between January 1997 and December 2007 for the surgical relief of left ventricular outflow tract obstruction. We excluded patients <18 years of age, those with an ejection fraction <50%, those with hypertensive heart disease of the elderly, and those with more than mild aortic or mitral stenosis. Clinical, echocardiographic, and Holter data were recorded. A composite end point of death, appropriate internal cardioverter defibrillator discharges, resuscitated from sudden death, documented stroke, and admission for congestive heart failure was recorded. During a mean follow-up of 6.2±3 years, 86 patients (12%) met the composite end point with 30-day, 1-year, and 2-year event rates of 0.7%, 2.8%, and 4.7%, respectively. The hard event rate (death, defibrillator discharge, and resuscitated from sudden death) at 30 days, 1 year, and 2 years was 0%, 1.5%, and 3%, respectively. Stepwise multivariable analysis identified residual postoperative atrial fibrillation (hazard ratio, 2.12; confidence interval, 1.37–3.34; P=0.001) and increasing age (hazard ratio, 1.49; confidence interval, 1.22–1.82; P=0.001) as independent predictors of long-term composite outcomes. Conclusions— Symptomatic adult hypertrophic cardiomyopathy patients undergoing surgery for the relief of left ventricular outflow tract obstruction have low event rates during long-term follow-up; worse outcomes are predicted by increasing age and the presence of residual atrial fibrillation during follow-up.

Exercise echocardiography in asymptomatic HCM: Exercise capacity, and not LV outflow tract gradient predicts long-term outcomes

OBJECTIVES This study sought to assess long-term outcomes in asymptomatic or minimally symptomatic patients with hypertrophic cardiomyopathy (HCM) who underwent exercise echocardiography, without invasive therapies for relief of left ventricular outflow tract (LVOT) obstruction. BACKGROUND Many HCM patients present with LVOT obstruction, mitral regurgitation (MR), and diastolic dysfunction, often requiring invasive therapies for symptomatic relief. However, a significant proportion of truly asymptomatic patients can be closely monitored. In HCM patients, exercise echocardiography has been shown to be a useful assessment of functional capacity and risk stratification. METHODS We included 426 HCM patients (44 ± 14 years; 78% men) undergoing exercise echocardiography, excluding hypertensive heart disease of elderly, ejection fraction <50% and invasive therapy (myectomy or alcohol ablation) during follow-up. Clinical, echocardiographic (LV thickness, LVOT gradient, and MR) and exercise variables (percent of age-sex predicted metabolic equivalents [METs] and heart rate recovery [HRR] at 1 min post-exercise) were recorded. A composite endpoint of death, appropriate internal defibrillator discharge, and admission for congestive heart failure was recorded. RESULTS Patients were asymptomatic or minimally symptomatic on history, but 82% of patients achieved <100% of age-sex predicted METs, and 43% had ≥II+ post-stress MR. The mean LV septal thickness, post-exercise LVOT gradient, and HRR were 2.0 ± 0.5 cm, 62 ± 47 mm Hg, and 31 ± 14 beats/min, respectively. During a mean follow-up of 8.7 ± 3 years, there were 52 events (12%). Patients achieving >100% of age-sex predicted METs had 1% event rate versus 12% in those achieving <85%. On stepwise multivariate survival analysis, percent of age-sex predicted METs (hazard ratio [HR]: 0.76; 95% confidence interval [CI]: 0.64 to 0.90), abnormal HRR (HR: 0.89; 95% CI: 0.82 to 0.97), and atrial fibrillation (HR: 2.73; 95% CI: 1.30 to 5.74) (overall, p < 0.001) independently predicted outcomes. CONCLUSIONS In asymptomatic or minimally symptomatic HCM patients, exercise stress testing provides excellent risk stratification, with a low event rate in patients achieving >100% of predicted METs.

Predictors of Long-Term Outcomes in Patients With Significant Myxomatous Mitral Regurgitation Undergoing Exercise Echocardiography

Background— Significant myxomatous mitral regurgitation leads to progressive left ventricular (LV) decline, resulting in congestive heart failure and death. Such patients benefit from mitral valve surgery. Exercise echocardiography aids in risk stratification and helps decide surgical timing. We sought to assess predictors of outcomes in such patients undergoing exercise echocardiography. Methods and Results— This is an observational study of 884 consecutive patients (age, 58±14 years; 67% men) with grade III+ or greater myxomatous mitral regurgitation who underwent exercise echocardiography between January 2000 and December 2011 (excluding functional mitral regurgitation, prior valvular surgery, hypertrophic cardiomyopathy, rheumatic valvular disease, or greater than mild mitral stenosis). Clinical and echocardiographic data (mitral regurgitation, LV ejection fraction, LV dimensions, right ventricular systolic pressure) and exercise variables (metabolic equivalents, heart rate recovery at 1 minute after exercise) were recorded. Composite events of death, myocardial infarction, stroke, and progression to congestive heart failure were recorded. Mean LV ejection fraction, indexed LV end-systolic dimension, resting right ventricular systolic pressure, peak stress right ventricular systolic pressure, metabolic equivalents achieved, and heart rate recovery were 58±5%, 1.6±0.4 mm/m2, 31±12 mm Hg, 46±17 mm Hg, 9.6±3, and 33±14 beats, respectively. During 6.4±4 years of follow-up, there were 87 events. On stepwise multivariable Cox analysis, percent of age/sex-predicted metabolic equivalents (hazard ratio, 0.99; 95% confidence interval, 0.98–0.99; P=0.005), heart rate recovery (hazard ratio, 0.29; 95% confidence interval, 0.17–0.50; P<0.001), resting right ventricular systolic pressure (hazard ratio, 1.03; 95% confidence interval, 1.004–1.05; P=0.02), atrial fibrillation (hazard ratio, 1.91; 95% confidence interval, 1.07–3.41; P=0.03), and LV ejection fraction (hazard ratio, 0.96; 95% confidence interval, 0.92–0.99; P=0.04) predicted outcomes. Conclusions— In patients with grade III+ or greater myxomatous mitral regurgitation undergoing exercise echocardiography, lower percent of age/sex-predicted metabolic equivalents, lower heart rate recovery, atrial fibrillation, lower LV ejection fraction, and high resting right ventricular systolic pressure predicted worse outcomes.

Predictors of long-term outcomes in patients with hypertrophic cardiomyopathy undergoing cardiopulmonary stress testing and echocardiography.

BACKGROUND Patients with hypertrophic cardiomyopathy (HCM) have exercise intolerance due to left ventricular outflow tract (LVOT) obstruction, mitral regurgitation, and left ventricular dysfunction. We sought to study predictors of outcomes in HCM patients undergoing cardiopulmonary stress testing (CPT). METHODS We studied 1,005 HCM patients (50 ± 14 years, 64% men, 77% on β-blockers) who underwent CPT with echocardiography. Clinical, echocardiographic, and exercise variables (peak oxygen consumption [VO2] and heart rate recovery [HRR] at first minute postexercise) were recorded. End point was a composite of death, appropriate defibrillator discharges, resuscitated sudden death, stroke, and heart failure admission. RESULTS Mean left ventricular ejection fraction (LVEF), postexercise LVOT gradient, and peak VO2 were 62% ± 6%, 92 ± 51 mm Hg, and 21 ± 6 mL kg(-1) min(-1), respectively. Despite 789 patients (78%) being in New York Heart Association classes I to II, only 8% achieved >100% age-gender predicted peak VO2, whereas 77% and 15% achieved 50% to 100% and <50%, respectively. Left ventricular outflow tract gradient ≥30 mm Hg was observed in 83% patients, whereas 23% had abnormal HRR. More than 5.5 ± 4 years, there were 94 (9%) events; 511 (50%) patients underwent surgery for LVOT obstruction. Multivariable Cox proportional analysis demonstrated % age-gender predicted peak VO2 (hazard ratio [HR] 0.96 [0.93-0.98]), normal vs abnormal HRR (HR 0.48 [0.32-0.73]), higher LVEF (HR 0.96 [0.93-0.98]), surgery (0.53 [0.33-0.83]), and atrial fibrillation (HR 1.65 [1.04-2.60]) were associated with outcomes (all P < .05). CONCLUSIONS In HCM patients undergoing CPT, a higher % of achieved age-gender predicted VO2 and surgical relief of LVOT obstruction were associated with better outcomes, whereas abnormal HRR, atrial fibrillation, and lower LVEF were associated with worse outcomes.

Characteristics and Outcomes of Patients With Severe Bioprosthetic Aortic Valve Stenosis Undergoing Redo Surgical Aortic Valve Replacement.

Background— With improved event-free survival of patients undergoing primary bioprosthetic aortic valve replacement (AVR), reoperation to relieve severe prosthetic aortic stenosis (PAS) is increasing. We sought to (1) identify of the characteristics of patients with severe bioprosthetic PAS undergoing redo AVR, and (2) assess the outcomes of these patients, along with factors associated with adverse outcomes. Methods and Results— We studied 276 patients with severe bioprosthetic PAS (64±16 years, 58% men) who underwent redo-AVR between 2000 and 2012 (excluding mechanical PAS, severe other valve disease, and transcatheter AVR). Society of Thoracic Surgeons score was calculated. Severe PAS was defined as AV area <0.8 cm2, mean AV gradient ≥40 mm Hg, or dimensionless index <0.25. A composite outcome of death and congestive heart failure admission was recorded. Mean Society of Thoracic Surgeons score and mean AV gradients were 8±8 and 53±17 mm Hg, whereas 28% had >II+ aortic regurgitation. Only 39% had an isolated redo AVR, the rest were combination surgeries (coronary bypass and/or aortic surgeries). At 4.2±3 years, 64 (23%) patients met the composite end point (48 deaths and 19 congestive heart failure admissions, 2.5% 30-day deaths). On multivariable Cox survival analysis, higher Society of Thoracic Surgeons score (hazard ratio, 1.35), higher grades of aortic regurgitation (hazard ratio, 1.29), and higher right ventricular systolic pressure (hazard ratio, 1.3) were associated with worse longer-term outcomes (all P<0.01). Conclusions— At an experienced center, in patients with severe bioprosthetic PAS undergoing redo AVR, the majority undergo combination surgeries but have excellent outcomes.

Importance of Exercise Capacity in Predicting Outcomes and Determining Optimal Timing of Surgery in Significant Primary Mitral Regurgitation

Background In primary mitral regurgitation (MR), exercise echocardiography aids in symptom evaluation and timing of mitral valve (MV) surgery. In patients with grade ≥3 primary MR undergoing exercise echocardiography followed by MV surgery, we sought to assess predictors of outcomes and whether delaying MV surgery adversely affects outcomes. Methods and Results We studied 576 consecutive such patients (aged 57±13 years, 70% men, excluding prior valve surgery and functional MR). Clinical, echocardiographic (MR, LVEF, indexed LV dimensions, RV systolic pressure) and exercise data (metabolic equivalents) were recorded. Composite events of death, MI, stroke, and congestive heart failure were recorded. Mean LVEF was 58±5%, indexed LV end‐systolic dimension was 1.7±0.5 mm/m2, rest RV systolic pressure was 32±13 mm Hg, peak‐stress RV systolic pressure was 47±17 mm Hg, and percentage of age‐ and gender‐predicted metabolic equivalents was 113±27. Median time between exercise and MV surgery was 3 months (MV surgery delayed ≥1 year in 28%). At 6.6±4 years, there were 53 events (no deaths at 30 days). On stepwise multivariable survival analysis, increasing age (hazard ratio of 1.07 [95% confidence interval, 1.03 to 1.12], P<0.01), lower percentage of age‐ and gender‐predicted metabolic equivalents (hazard ratio of 0.82 [95% confidence interval, 0.71 to 0.94], P=0.007), and lower LVEF (0.94 [0.89 to 0.99], P=0.04) independently predicted outcomes. In patients achieving >100% predicted metabolic equivalents (n=399), delaying surgery by ≥1 year (median of 28 months) did not adversely affect outcomes (P=0.8). Conclusion In patients with primary MR that underwent exercise echocardiography followed by MV surgery, lower achieved metabolic equivalents were associated with worse long‐term outcomes. In those with preserved exercise capacity, delaying MV surgery by ≥1 year did not adversely affect outcomes.

Impact of Duration of Mitral Regurgitation on Outcomes in Asymptomatic Patients With Myxomatous Mitral Valve Undergoing Exercise Stress Echocardiography

Background Significant mitral regurgitation (MR) typically occurs as holosystolic (HS) or mid‐late systolic (MLS), with differences in volumetric impact on the left ventricle (LV). We sought to assess outcomes of degenerative MR patients undergoing exercise echocardiography, separated based on MR duration (MLS versus HS). Methods and Results We included 609 consecutive patients with ≥III+myxomatous MR undergoing exercise echocardiography: HS (n=487) and MLS (n=122). MLS MR was defined as delayed appearance of MR signal during mid‐late systole on continuous‐wave Doppler while HS MR occurred throughout systole. Composite events of death and congestive heart failure were recorded. Compared to MLS MR, HS MR patients were older (60±14 versus 53±14 years), more were males (72% versus 53%), and had greater prevalence of atrial fibrillation (16% versus 7%; all P<0.01). HS MR patients had higher right ventricular systolic pressure (RVSP) at rest (33±11 versus 27±9 mm Hg), more flail leaflets (36% versus 6%), and a lower number of metabolic equivalents (METs) achieved (9.5±3 versus 10.5±3), compared to the MLS MR group (all P<0.05). There were 54 events during 7.1±3 years of follow‐up. On step‐wise multivariable analysis, HS versus MLS MR (HR 4.99 [1.21 to 20.14]), higher LV ejection fraction (hazard ratio [HR], 0.94 [0.89 to 0.98]), atrial fibrillation (HR, 2.59 [1.33 to 5.11]), higher RVSP (HR, 1.05 [1.03 to 1.09]), and higher percentage of age‐ and gender‐predicted METs (HR, 0.98 [0.97 to 0.99]) were independently associated with adverse outcomes (all P<0.05). Conclusion In patients with ≥III+myxomatous MR undergoing exercise echocardiography, holosystolic MR is associated with adverse outcomes, independent of other predictors.

Incremental Prognostic Use of Left Ventricular Global Longitudinal Strain in Asymptomatic/Minimally Symptomatic Patients With Severe Bioprosthetic Aortic Stenosis Undergoing Redo Aortic Valve Replacement.

Background— With improved survival of patients undergoing primary bioprosthetic aortic valve replacement (AVR), reoperation to relieve severe prosthetic aortic stenosis (PAS) is increasing. Timing of redo surgery in asymptomatic/minimally symptomatic patients remains controversial. Left ventricular (LV) global longitudinal strain (GLS) is a marker of subclinical LV dysfunction. In asymptomatic/minimally symptomatic patients with severe PAS undergoing redo AVR, we sought to determine whether LV-GLS provides incremental prognostic use. Methods and Results— We studied 191 patients with severe bioprosthetic PAS (63±16 years, 58% men) who underwent redo AVR between 2000 and 2012 (excluding mechanical PAS, severe other valve disease transcatheter AVR, and LV ejection fraction <50%). Society of Thoracic Surgeons score was calculated. Standard echocardiography data were obtained. LV-GLS was measured on 2-, 3-, and 4-chamber views using velocity vector imaging. Severe PAS was defined as aortic valve area <0.8 cm2, mean aortic valve gradient ≥40 mm Hg, and dimensionless index <0.25. A composite outcome of death and congestive heart failure admission was recorded. At baseline, mean Society of Thoracic Surgeons score, LV ejection fraction, mean aortic valve gradients, and right ventricular systolic pressure were 7±6, 58±6%, 54±10 mm Hg and 40±14 mm Hg, whereas 50% had >2+ aortic regurgitation. Median LV-GLS was −14.2% (−11.4, −17.1%). At 4.2±3 years, 41 (22%) patients met the composite end point (2.5% deaths and 1% strokes at 30 days postoperatively). On multivariable Cox survival analysis, LV-GLS was independently associated with longer-term composite events (hazard ratio, 1.21; 95% confidence interval, 1.10–1.33), P<0.01. The C statistic for the clinical model (Society of Thoracic Surgeons score, degree of aortic regurgitation, and right ventricular systolic pressure) was 0.64 (95% confidence interval 0.54–0.79), P<0.001. Addition of LV-GLS to the clinical model increased the C statistic significantly to 0.71 (95% confidence interval 0.58–0.81), P<0.001. Conclusions— In asymptomatic/minimally symptomatic patients with severe bioprosthetic PAS undergoing redo AVR, baseline LV-GLS provides incremental prognostic use over established predictors and could potentially aid in surgical timing and risk stratification.

Impact of additive mitral valve surgery to coronary artery bypass grafting on mortality in patients with coronary artery disease and ischaemic mitral regurgitation: a systematic review and meta-analysis of randomized trials and observational studies

Aims Treatment of ischaemic mitral regurgitation (IMR) remains controversial. While IMR is associated with worse outcomes, randomized controlled trials (RCTs) and observational studies provided conflicting evidence regarding the benefit of mitral valve replacement (MVR) or repair (MVr) in addition to coronary artery bypass grafting (CABG). We conducted a meta-analysis incorporating data from published RCTs and observational studies comparing CABG vs. CABG + MVR/MVr. Methods and results We searched PubMed, MEDLINE, Embase, Ovid, and Cochrane for RCTs and observational studies comparing CABG (Group 1) vs. CABG + MVR/MVr (Group 2). Outcome was 30-day and 1-year mortality after surgical intervention. Mantel-Haenszel odds ratio (OR) was calculated using random-effects meta-analysis for the outcome. Heterogeneity was assessed by I2 statistics. Four RCTs and 11 observational studies met the inclusion criteria (5781 patients, 507 in RCTs, 5274 in observational studies). Group 1 vs. 2 weighted mean left ventricular ejection fraction in RCTs and combined RCTs/observational studies was 41.5 ± 12.3 vs. 40.3 ± 10.4% ( P -value = 0.24) and 45.5 ± 7.2 vs. 38 ± 10% ( P -value < 0.001), respectively. In RCTs, there was no difference in 30-day [OR: 0.95, 95% confidence interval (95% CI): 0.30-3.08, P = 0.94] or 1-year (OR: 0.90, 95% CI: 0.43-1.87, P = 0.78) mortality, respectively. For combined RCTs/observational studies, there was no difference in mortality at 30 days (OR: 0.67, 95% CI: 0.43-1.04, P = 0.08) or at 1 year (OR: 0.90, 95% CI: 0.7-1.15, P = 0.39). Conclusion In a meta-analysis of RCTs and observational studies of IMR patients, the addition of MVR/MVr to CABG did not improve survival.

Stress echocardiography in valvular heart disease: a current appraisal

Stress echocardiography is increasingly used in the management of patients with valvular heart disease and can aid in evaluation, risk stratification and clinical decision making in these patients. Evaluation of symptoms, exercise capacity and changes in blood pressure can be done during the exercise portion of the test, whereas echocardiographic portion can reveal changes in severity of disease, pulmonary artery pressure and left ventricular function in response to exercise. These parameters, which are not available at rest, can have diagnostic and prognostic importance. In this article, we will review the indications and diagnostic implications, prognostic implications, and clinical impact of stress echocardiography in decision making and management of patients with valvular heart disease.