[Show abstract][Hide abstract] ABSTRACT: Background
Hypertrophic cardiomyopathy (HCM) is a primary myopathic process in which regional left ventricular dysfunction may exist without overt global left ventricular dysfunction. In obstructive HCM patients who underwent surgical myectomy (SM), we sought to determine if there is a significant association between echocardiographic longitudinal strain, histopathology, and in vitro myocardial performance (resting tension and developed tension) of the surgical specimen.
Methods and Results
HCM patients (n=122, 54±14 years, 54% men) undergoing SM were prospectively recruited. Longitudinal systolic strain and diastolic strain rates were measured at that basal septum (partially removed at SM) by using velocity vector imaging on preoperative echocardiography. Semiquantitative histopathologic grading of myocyte disarray and fibrosis and in vitro measurements of resting tension and developed tension were made in septal tissue obtained at SM. Mean basal septal systolic strain and diastolic strain rate were −8.3±5% and 0.62±0.4/s, while mild or greater degree of myocyte disarray and interstitial fibrosis were present in 85% and 87%, respectively. Mean resting tension and developed tension were 2.8±1 and 1.4±0.8 g/mm2. On regression analysis, basal septal systolic strain, diastolic strain rate, disarray, and fibrosis were associated with developed tension (β=0.19, 0.20, −0.33, and −0.40, respectively, all P<0.01) and resting tension (β=0.21, 0.22, −0.25, and −0.28, respectively, all P<0.01).
In obstructive HCM patients who underwent SM, left ventricular mechanics (echocardiographic longitudinal systolic strain and diastolic strain rates), assessed at the basal septum (myocardium removed during myectomy) and histopathologic findings characteristic for HCM (disarray and fibrosis) were significantly associated with in vitro myocardial resting and developed contractile performance.
Journal of the American Heart Association 10/2014; 3(6). DOI:10.1161/JAHA.114.001269 · 2.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patients with obstructive hypertrophic cardiomyopathy (HC) have various left ventricular (LV) shapes: reverse septal curvature (RSC, commonly familial), sigmoid septum (SS, common in hypertensives), and concentric hypertrophy (CH). Longitudinal (systolic and early diastolic) strain rate (SR) is sensitive in detecting regional myocardial dysfunction. We sought to determine differences in longitudinal SR of patients with obstructive HC, based on LV shapes. We studied 199 consecutive patients with HC (50% men) referred for surgical myectomy. Clinical and echocardiographic parameters were recorded. LV shapes were classified on echocardiography, using basal septal 1/3 to posterior wall ratio: RSC = ratio >1.3 (extending to mid and distal septum), SS = ratio >1.3 (extending only to basal 1/3), and concentric = ratio ≤1.3. Longitudinal systolic and early diastolic SRs were measured from apical 4- and 2-chamber views (VVI 2.0; Siemens, Erlangen). Distribution of RSC, SS, and CH was 50%, 28%, and 22%, respectively. Patients with RSC were significantly younger (47 ± 12 vs 64 ± 10 and 57 ± 11, respectively) with lower hypertension (40% vs71% and 67%, respectively) than patients with SS or CH (both p <0.001). Patients with RSC had lower global systolic (-0.99 ± 0.3 vs -1.05 ± 0.3 and -1.17 ± 0.3) and early diastolic SR (0.95 ± 0.4 vs 0.98 ± 0.3 and 1.16 ± 0.4) versus patients with SS and CH (in 1/s, both p <0.01), despite being much younger and less hypertensive. RSC was associated with abnormal global LV systolic (beta 0.16) and early diastolic (beta -0.17) SR (both p <0.01). In conclusion, patients with HC with RCS have significantly abnormal LV mechanics, despite being younger and less hypertensive. A combination of LV mechanics and shapes could help differentiate between genetically mediated and other causes of obstructive HC.
The American Journal of Cardiology 06/2014; 113(11):1879-85. DOI:10.1016/j.amjcard.2014.03.020 · 3.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We 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.
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.
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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: Hypertrophic cardiomyopathy (HCM) is histopathologically characterized by myocyte hypertrophy, disarray, interstitial fibrosis, and small intramural coronary arteriole dysplasia, which contribute to disease progression. Longitudinal systolic and early diastolic strain rate (SR) measurements by speckle tracking echocardiography are sensitive markers of regional myocardial function. We sought to determine the association between septal SR and histopathologic findings in symptomatic HCM patients who underwent surgical myectomy.
We studied 171 HCM patients (documented on histopathology) who underwent surgical myectomy to relieve left ventricular outflow tract obstruction. Various clinical and echocardiographic parameters were recorded. Segmental longitudinal systolic and early diastolic SRs (of the septal segment removed at myectomy) were measured from apical 4- and 2-chamber views (VVI 2.0; Siemens, Erlangen, Germany). Histopathologic myocyte hypertrophy, disarray, small intramural coronary arteriole dysplasia, and interstitial fibrosis were classified as none, mild (1%-25%), moderate (26%-50%), and severe (>50%).
The mean age was 53 ± 14 years (52% men, ejection fraction 62% ± 5%, mean left ventricular outflow tract gradient 102 ± 39 mm Hg, and basal septal thickness of 2.2 ± 0.5 cm). Mean longitudinal systolic and early diastolic SRs were -0.91 ± 0.5 and 0.82 ± 0.5 (1/s), respectively. There was an inverse association between systolic and early diastolic septal SR and degree of myocyte hypertrophy, disarray, and interstitial fibrosis (all P < .05). There was no association between histopathologic characteristics and other echocardiography parameters. On multivariable regression analysis, myocyte disarray and echocardiographic septal hypertrophy were associated with systolic and early diastolic septal SR (P < .05).
In HCM patients, there is inverse association between various histopathologic findings and septal SR. Strain rate might potentially provide further insight into HCM pathophysiology.
American heart journal 09/2013; 166(3):503-11. DOI:10.1016/j.ahj.2013.06.011 · 4.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: We report the predictors of long-term outcomes of symptomatic hypertrophic cardiomyopathy (HCM) patients undergoing surgical relief of left ventricular outflow tract (LVOT) obstruction. METHODS AND RESULTS: We studied 699 consecutive HCM patients with severe symptomatic LVOT obstruction (47±11 years, 63% male) intractable to maximal medical therapy, that were referred to a tertiary hospital between 1/1997 and 12/2007 for surgical relief of LVOT obstruction. We excluded patients < 18 years and those with ejection fraction < 50%, hypertensive heart disease of elderly and > mild aortic or mitral stenosis. Clinical, echocardiographic, and Holter data was recorded. A composite endpoint of death, appropriate internal cardioverter defibrillator discharges, resuscitated 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 endpoint with 30-day, 1-year and 2-year event rate of 0.7%, 2.8% and 4.7%, respectively. The hard event rate (death, defibrillator discharge and resuscitated sudden death) at 30-day, 1-year and 2-years was 0%, 1.5% and 3%, respectively. Stepwise multivariable analysis identified residual postoperative AF (Hazard ratio 2.12 [1.37-3.34] p=0.001), and increasing age (Hazard ratio 1.49 [1.22-1.82] p=0.001) as independent predictors of long-term composite outcomes. CONCLUSIONS: Symptomatic adult HCM patients undergoing surgery for relief of LVOT obstruction have low event rate during long-term follow up; with worse outcomes predicted by increasing age and presence of residual AF during follow up.
[Show abstract][Hide abstract] ABSTRACT: Diastolic dysfunction (DD) is often incriminated in the symptomatology of patients with hypertrophic cardiomyopathy (HCM), but with limited supporting data. This study sought to assess the relationship between baseline diastolic function and exercise capacity in patients with HCM.
Tertiary referral centre from Cleveland, Ohio, USA.
695 consecutive patients with a diagnosis of HCM who underwent exercise stress echocardiography between 1996 and 2011. PRIMARY AND SECONDARY OUTCOME MEASURES: Diastolic function was reassessed from the resting echocardiograms by two blinded board-certified cardiologists. Maximal metabolic equivalents (MET) were extracted from the records. Multivariate regression analysis was performed to determine independent predictors of METs achieved.
Of 695 patients, 130 were excluded because of inability to assess diastolic function. There was no significant difference in maximal METs achieved between those excluded and included in the analysis (p=0.80). There were 495 remaining patients with a mean age (SD) of 50 (15) years, and 32% women among whom 102 (21%) had normal diastolic function, 243 (49%) stage 1 DD; 131 (26%) stage 2 DD and 19 (4%) stage 3 DD. Patients with advanced DD had lower maximal METs achieved compared with those with normal diastolic function (OR 3.18(1.96 to 5.14) for stage 1 versus normal, and 3.21(1.89 to 5.43) for stage ≥2 versus normal, p<0.0001 for both). After adjustment for demographics, comorbidities, echocardiographic parameters and haemodynamics, baseline DD was not an independent predictor of maximal METs achieved.
Although baseline DD is common in patients with HCM, it does not predict maximal METs achieved beyond traditional risk factors.
BMJ Open 10/2012; 2(6). DOI:10.1136/bmjopen-2012-002104 · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hypertrophic cardiomyopathy (HCM) is a complex and common genetic disease. The left ventricular outflow tract obstruction is an important determinant of symptoms and outcomes. Its pathophysiology is determined by the complex interaction of the mitral valve, papillary muscles, chordae tendinea, and interventricular septum. The knowledge and importance of the mitral valve apparatus in the physiology of the HCM are expanding with the new imaging modalities, in particular, cardiac magnetic resonance. Several abnormalities of the mitral apparatus have been described in patients with HCM including abnormal papillary muscles, leaflets' lengths, and mitral regurgitation. Ignoring these variables can lead to unnecessary or incomplete surgical treatments and worse outcomes. This review discusses the role of the mitral apparatus in HCM with a focus on a multimodality imaging approach and the clinical importance of each abnormality.
[Show abstract][Hide abstract] ABSTRACT: Exercise capacity in patients with hypertrophic cardiomyopathy (HCM) varies despite similar diastolic dysfunction, left ventricular outflow tract (LVOT) obstruction and mitral regurgitation (MR). Pulse wave velocity (PWV), determined by cardiac magnetic resonance (CMR), measures aortic stiffness and is abnormal in patients with HCM in comparison with controls.
To determine potential clinical and imaging predictors of peak oxygen consumption (pVO(2)) in patients with HCM.
Fifty newly referred patients with HCM (62% men, 44+/-13 years, 90% receiving optimal drugs, 18% hypertensive) underwent Doppler echocardiography (transthoracic echocardiography (TTE)), cardiopulmonary exercise testing and CMR for symptom evaluation. TTE variables (diastology, post exercise MR and LVOT gradient (mmHg)), pVO(2) (ml/kg/min) and CMR variables (PWV (aortic path length between mid- and descending aorta/time delay between arrival of the foot of the pulse wave between two points, m/s), and LV volumetric indices) were measured.
After exercise LVOT gradient, MR, deceleration time and pVO(2) were 104+/-52, 1+/-1, 240+/-79 ms, and 25+/-6, respectively. Mean basal septal thickness (cm), PWV, EF, ESV index (ml/m(2)), EDV index (ml/m(2)) and LV mass index (g/m(2)) were 1.9+/-0.5, 9.3+/-7, 64%+/-7, 32+/-9, 87+/-17 and 112+36, respectively. Multiple regression analyses showed that only age (beta=-0.38, p=0.004) and PWV (beta=-0.33, p=0.01) predicted pVO(2).
In patients with HCM, age and PWV are predictors of pVO(2), independent of LV thickness, LVOT gradient and diastolic indices. Aortic stiffness potentially has a role in evaluation of symptoms of patients with HCM.
[Show abstract][Hide abstract] ABSTRACT: In patients with hypertrophic cardiomyopathy with bifid hypermobile papillary muscles and a dynamic left ventricular outflow tract gradient, we performed surgical papillary muscle reorientation, fixing the mobile papillary muscle to the posterior left ventricle to reduce mobility. We report the outcomes of patients with hypertrophic cardiomyopathy undergoing surgical papillary muscle reorientation versus those of patients undergoing standard surgical procedures.
We studied 204 consecutive patients with hypertrophic cardiomyopathy undergoing surgical intervention (after consensus decision) for symptomatic left ventricular outflow tract gradient. Preoperative and postoperative maximal (resting/provocable) left ventricular outflow tract gradients were recorded by using echocardiographic analysis.
The population was divided into 3 groups: (1) isolated myectomy (n = 143; age, 54 +/- 14 years; 48% men), (2) myectomy plus mitral valve repair/replacement (n = 39; age, 54 +/- 13 years; 54% men), and (3) papillary muscle reorientation with or without myectomy (n = 22; age, 50 +/- 14 years; 59% men). The mean preoperative (103 +/- 32, 103 +/- 32, and 114 +/- 36 mm Hg; P = .3) and predischarge (15 +/- 18, 14 +/- 14, and 16 +/- 21 mm Hg; P = .9) maximal left ventricular outflow tract gradients were similar. There were no deaths either in the hospital or at 30 days. At a median follow-up of 166 days (interquartile range, 74-343 days), 21 of 22 patients in group 3 were asymptomatic. One patient in group 3 had a symptomatic left ventricular outflow tract gradient (87 mm Hg) requiring mitral valve replacement.
In patients with hypertrophic cardiomyopathy with bifid hypermobile papillary muscles (even with a basal septal thickness <1.5 cm), papillary muscle reorientation reduces the symptomatic left ventricular outflow tract gradient. Long-term outcomes need to be ascertained.
The Journal of thoracic and cardiovascular surgery 08/2010; 140(2):317-24. DOI:10.1016/j.jtcvs.2009.10.045 · 3.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to perform a systematic review and meta-analysis of comparative studies to compare outcomes of septal ablation (SA) with septal myectomy (SM) for treatment of hypertrophic obstructive cardiomyopathy (HOCM).
SM is considered the gold standard for treatment of HOCM. However, SA has emerged as an attractive therapeutic alternative.
A Medline search using standard terms was conducted to determine eligible studies. Due to a lack of randomized control trials, we included observational studies for review.
Twelve studies were found eligible for review. No significant differences between short-term (risk difference [RD]: 0.01; 95% confidence interval [CI]: -0.01 to 0.03) and long-term mortality (RD: 0.02; 95% CI: -0.05 to 0.09) were found between the SA and SM groups. In addition, no significant differences could be found in terms of post-intervention functional status as well as improvement in New York Heart Association functional class, ventricular arrhythmia occurrence, re-interventions performed, and post-procedure mitral regurgitation. However, SA was found to increase the risk of right bundle branch block (RBBB) (pooled odds ratio [OR]: 56.3; 95% CI: 11.6 to 273.9) along with need for permanent pacemaker implantation post-procedure (pooled OR: 2.6; 95% CI: 1.7 to 3.9). Although the efficacy of both SA and SM in left ventricular outflow tract gradient (LVOTG) reduction seems comparable, there is a small yet significantly higher residual LVOTG amongst the SA group patients as compared with the SM group patients.
SA does seem to show promise in treatment of HOCM owing to similar mortality rates as well as functional status compared with SM; however, the caveat is increased conduction abnormalities and a higher post-intervention LVOTG. The choice of treatment strategy should be made after a thorough discussion of the procedures with the individual patient.
Journal of the American College of Cardiology 02/2010; 55(8):823-34. DOI:10.1016/j.jacc.2009.09.047 · 15.34 Impact Factor