Diagnostic and Prognostic Value of Myocardial Work Indices for Identification of Cancer Therapy-Related Cardiotoxicity.

BACKGROUND: Echocardiographic global longitudinal strain (GLS) is a useful measure for detection of cancer treatment-related cardiac dysfunction (CTRCD) but is influenced by blood pressure changes. This limitation may be overcome by assessment of myocardial work (MW), which incorporates blood pressure into the calculation. OBJECTIVES: This work aims to determine whether myocardial work indices (MWIs) can help diagnose or prognosticate CTRCD. METHODS: In this prospective cohort study, 136 women undergoing anthracycline and trastuzumab treatment for HER2+ breast cancer, underwent serial echocardiograms and cardiac magnetic resonance pre- and post-anthracycline and every 3 months during trastuzumab. GLS, global work index (GWI), global constructive work (GCW), global wasted work, and global work efficiency were measured. CTRCD was defined with cardiac magnetic resonance. Generalized estimating equations quantified the association between changes in GLS and MWIs and CTRCD at the current (diagnosis) and subsequent visit (prognosis). Regression tree analysis was used to explore the combined use of GLS and MW for the diagnostic/prognostic assessment of CTRCD. RESULTS: Baseline left ventricular ejection fraction (LVEF) was 63.2 ± 4.0%. Thirty-seven (27.2%) patients developed CTRCD. An absolute change in GLS (standardized odds ratio [sOR]: 1.97 [95% CI: 1.07-3.66]; P = 0.031) and GWI (sOR: 1.73 [95% CI: 1.04-2.85]; P = 0.033) were associated with concurrent CTRCD. An absolute change in GLS (sOR: 1.79 [95% CI: 1.22-2.62]; P = 0.003), GWI (sOR: 1.67 [95% CI: 1.20-2.32]; P = 0.003), and GCW (sOR: 1.65 [95% CI: 1.17-2.34]; P = 0.005) were associated with subsequent CTRCD. Change in GWI and GCW demonstrated incremental value over GLS and clinical factors for the diagnosis of concurrent CTRCD. In a small group with a GLS change <3.3% (absolute), and a >21 mm Hg reduction in systolic blood pressure, worsening of GWI identified patients with higher probability of concurrent CTRCD (24.0% vs 5.2%). MWIs did not improve identification of subsequent CTRCD beyond knowledge of GLS change. CONCLUSIONS: GLS can be used to diagnose and prognosticate cardiac magnetic resonance (CMR) defined CTRCD, with additional value from MWIs in selected cases. (Evaluation of Myocardial Changes During Breast Adenocarcinoma Therapy to Detect Cardiotoxicity Earlier With MRI [EMBRACE-MRI]; NCT02306538).

A Combined Echocardiography Approach for the Diagnosis of Cancer Therapy-Related Cardiac Dysfunction in Women With Early-Stage Breast Cancer.

IMPORTANCE: Diagnosis of cancer therapy-related cardiac dysfunction (CTRCD) remains a challenge. Cardiovascular magnetic resonance (CMR) provides accurate measurement of left ventricular ejection fraction (LVEF), but access to repeated scans is limited. OBJECTIVE: To develop a diagnostic model for CTRCD using echocardiographic LVEF and strain and biomarkers, with CMR as the reference standard. DESIGN, SETTING, AND PARTICIPANTS: In this prospective cohort study, patients were recruited from University of Toronto-affiliated hospitals from November 2013 to January 2019 with all cardiac imaging performed at a single tertiary care center. Women with human epidermal growth factor receptor 2 (HER2)-positive early-stage breast cancer were included. The main exclusion criterion was contraindication to CMR. A total of 160 patients were recruited, 136 of whom completed the study. EXPOSURES: Sequential therapy with anthracyclines and trastuzumab. MAIN OUTCOMES AND MEASURES: Patients underwent echocardiography, high-sensitivity troponin I (hsTnI), B-type natriuretic peptide (BNP), and CMR studies preanthracycline and postanthracycline every 3 months during and after trastuzumab therapy. Echocardiographic measures included 2-dimensional (2-D) LVEF, 3-D LVEF, peak systolic global longitudinal strain (GLS), and global circumferential strain (GCS). LVEF CTRCD was defined using the Cardiac Review and Evaluation Committee Criteria, GLS or GCS CTRCD as a greater than 15% relative change, and abnormal hsTnI and BNP as greater than 26 pg/mL and ≥ 35 pg/mL, respectively, at any follow-up point. Combinations of echocardiographic measures and biomarkers were examined to diagnose CMR CTRCD using conditional inference tree models. RESULTS: Among 136 women (mean [SD] age, 51.1 [9.2] years), CMR-identified CTRCD occurred in 37 (27%), and among those with analyzable images, in 30 of 131 (23%) by 2-D LVEF, 27 of 124 (22%) by 3-D LVEF, 53 of 126 (42%) by GLS, 61 of 123 (50%) by GCS, 32 of 136 (24%) by BNP, and 14 of 136 (10%) by hsTnI. In isolation, 3-D LVEF had greater sensitivity and specificity than 2-D LVEF for CMR CTRCD while GLS had greater sensitivity than 2-D or 3-D LVEF. Regression tree analysis identified a sequential algorithm using 3-D LVEF, GLS, and GCS for the optimal diagnosis of CTRCD (area under the receiver operating characteristic curve, 89.3%). The probability of CTRCD when results for all 3 tests were negative was 1.0%. When 3-D LVEF was replaced by 2-D LVEF in the model, the algorithm still performed well; however, its primary value was to rule out CTRCD. Biomarkers did not improve the ability to diagnose CTRCD. CONCLUSIONS AND RELEVANCE: Using CMR CTRCD as the reference standard, these data suggest that a sequential approach combining echocardiographic 3-D LVEF with 2-D GLS and 2-D GCS may provide a timely diagnosis of CTRCD during routine CTRCD surveillance with greater accuracy than using these measures individually. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02306538.

Clinical, Echocardiographic, and Biomarker Associations With Impaired Cardiorespiratory Fitness Early After HER2-Targeted Breast Cancer Therapy.

BACKGROUND: Cardiorespiratory fitness (CRF) is reduced in cancer survivors and predicts cardiovascular disease (CVD)-related and all-cause mortality. However, routine measurement of CRF is not always feasible. OBJECTIVES: The purpose of this study was to identify clinical, cardiac biomarker, and imaging measures associated with reduced peak oxygen consumption (VO2peak) (measure of CRF) early post-breast cancer therapy to help inform CVD risk. METHODS: Consecutive women with early-stage HER2+ breast cancer receiving anthracyclines and trastuzumab were recruited prospectively. Within 6 ± 2 weeks of trastuzumab completion, we collected clinical information, systolic/diastolic echocardiographic measures, high-sensitivity troponin I, B-type natriuretic peptide, and VO2peak using a cycle ergometer. Regression models were used to examine the association between VO2peak and clinical, imaging, and cardiac biomarkers individually and in combination. RESULTS: Among 147 patients (age 52.2 ± 9.3 years), the mean VO2peak was 19.1 ± 5.0 mL O2·kg-1·min-1 (84.2% ± 18.7% of predicted); 44% had a VO2peak below threshold for functional independence (<18 mL O2·kg-1·min-1). In multivariable analysis, absolute global longitudinal strain (GLS) (ß = 0.58; P = 0.007), age per 10 years (ß: -1.61; P = 0.001), and E/e' (measure of diastolic filling pressures) (ß = -0.45; P = 0.038) were associated with VO2peak. GLS added incremental value in explaining the variability in VO2peak. The combination of age ≥50 years, E/e' ≥7.8, and GLS <18% identified a high probability (85.7%) of compromised functional independence, whereas age <50 years, E/e' <7.8, and GLS ≥18% identified a low probability (0%). High-sensitivity troponin I and B-type natriuretic peptide were not associated with VO2peak. CONCLUSIONS: Readily available clinical measures were associated with VO2peak early post-breast cancer therapy. A combination of these parameters had good discrimination to identify patients with compromised functional independence and potentially increased future CVD risk.

Isolated septal myectomy for hypertrophic obstructive cardiomyopathy: an update on the Toronto General Hospital experience.

BACKGROUND: Isolated septal myectomy is considered the gold standard for refractory left ventricular outflow tract (LVOT) obstruction at centers with dedicated hypertrophic obstructive cardiomyopathy (HOCM) surgeons. In this paper, we provide an update on the Toronto General Hospital (TGH) experience for isolated septal myectomy and comment on the safety and efficacy of myectomy in patients with thin basal septal thickness at our institution. METHODS: We retrospectively reviewed all patients undergoing surgical myectomy at our institution from January 2012 to August 2016. We analyzed patient characteristics, intraoperative variables, pre- and post-procedural echocardiographic parameters, and key outcomes including post-operative stroke, renal failure, iatrogenic ventricular septal defect (VSD), post-procedure insertion of permanent pacemaker, and mortality. RESULTS: At our institution, 150 isolated septal myectomy surgeries were performed over the study period. Preoperative echocardiography demonstrated an average basal septal thickness of 2.10±0.43 cm with a resting gradient of 67±37 mmHg and a provoked gradient of 89±40 mmHg. Fifty percent of patients had significant systolic anterior motion (SAM) of their mitral valve and 53% had associated moderate to severe mitral regurgitation (MR). Of note, 24% of patients had a thin septum of ≤1.7 cm. Discharge echocardiograms demonstrated significant septal reduction to an average basal septal thickness of 1.04±0.26 (P<0.05), with negligible resting and provokable LVOT gradients. At the time of discharge, none of the patients had significant SAM and only 5.3% of patients had residual greater than mild MR. Patients undergoing isolated myectomy with a thin basal septum had similar outcomes to those with a >1.7 cm septal thickness. In our contemporary cohort, there were no iatrogenic VSDs, 5.3% of patients required a permanent pacemaker and there was one early death. CONCLUSIONS: Our cohort demonstrates that isolated septal myectomy remains a safe and effective operation that can achieve excellent results, irrespective of basal septal thickness, when done by experienced surgeons in a dedicated hypertrophic cardiomyopathy (HCM) center.

Cux1 promotes cell proliferation and polycystic kidney disease progression in an ADPKD mouse model.

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common monogenic hereditary disorders in humans characterized by fluid-filled cysts, primarily in the kidneys. Cux1, a cell cycle regulatory gene highly expressed during kidney development, is elevated in the cyst-lining cells of Pkd1 mutant mice, and in human ADPKD cells. However, forced expression of Cux1 is insufficient to induce cystic disease in transgenic mice or to induce rapid cyst formation after cilia disruption in the kidneys of adult mice. Here we report a double mutant mouse model that has a conditional deletion of the Pkd1 gene in the renal collecting ducts together with a targeted mutation in the Cux1 gene (Pkd1CD;Cux1tm2Ejn). While kidneys isolated from newborn Pkd1CD mice exhibit cortical and medullary cysts, kidneys isolated from newborn Pkd1CD;Cux1tm2Ejn-/- mice did not show any cysts. Because Cux1tm2Ejn-/- are perinatal lethal, we evaluated Pkd1CD mice that were heterozygote for the Cux1 mutation. Similar to the newborn Pkd1CD;Cux1tm2Ejn-/- mice, newborn Pkd1CD;Cux1tm2Ejn+/- mice did not show any cysts. Comparison of Pkd1CD and Pkd1CD;Cux1tm2Ejn+/- mice at later stages of development showed a reduction in the severity of PKD in the Pkd1CD;Cux1tm2Ejn+/- mice. Moreover, we observed an increase in expression of the cyclin kinase inhibitor p27, a target of Cux1 repression, in the rescued collecting ducts. Taken together, our results suggest that Cux1 expression in PKD is not directly involved in cystogenesis but promotes cell proliferation required for expansion of existing cysts, primarily by repression of p27.

Quantitative Modeling of the Mitral Valve by Three-Dimensional Transesophageal Echocardiography in Patients Undergoing Mitral Valve Repair: Correlation with Intraoperative Surgical Technique.

BACKGROUND: Mitral valve (MV) repair is the procedure of choice for patients with degenerative MV disease (DMVD) with severe mitral regurgitation. The aim of this study was to identify specific quantitative MV parameters from preoperative three-dimensional (3D) transesophageal echocardiography that are associated with the length of the mitral annuloplasty band implanted and the performance of leaflet resection in patients with DMVD undergoing MV repair. METHODS: Ninety-four patients (mean age, 60 ± 11 years; 68% men) referred for MV surgery with adequate-quality preoperative 3D transesophageal echocardiographic studies were retrospectively identified. Parametric maps of the MV were generated using semiautomated MV modeling software. Annular and valvular parameters were measured and indexed to body surface area. The implanted annuloplasty band size and leaflet resection were determined on the basis of surgical reports. RESULTS: Three-dimensional annular circumference correlated best (r = 0.74) with the implanted annuloplasty band length and remained an independent predictor on multivariate linear regression analysis. A third of our cohort (n = 33) had posterior leaflet resection. On receiver operating characteristic curve analysis, P2 segment length ≥ 20 mm (area under the curve, 0.86; sensitivity, 88%; specificity, 74%) and P2 leaflet area ≥ 3.4 cm(2) (area under the curve, 0.84; sensitivity, 85%; specificity, 74%) best discriminated the need for leaflet resection. CONCLUSIONS: In DMVD, quantitative 3D annular circumference obtained from semiautomatically generated parametric maps of the MV from 3D transesophageal echocardiographic data was associated with the surgically implanted annuloplasty band length, while P2 leaflet length ≥ 20 mm and area ≥ 3.4 cm(2) were associated with the performance of leaflet resection. These parameters should be further investigated for preoperative planning in patients with DMVD undergoing MV repair.

Short and medium term outcomes of surgery for patients with hypertrophic obstructive cardiomyopathy.

BACKGROUND: We report one surgeon's experience of corrective surgery for hypertrophic obstructive cardiomyopathy (HOCM) over a 10-year span and comment on factors that influence longer term outcomes. Septal myectomy (SM) and adjunctive procedures, including shortening of the aorta, a novel technique in HOCM patients, are described. METHODS: Perioperative data were obtained by retrospective review of institutional surgical databases between 2001 and 2011. Review of most recent echocardiogram and clinical status by telephone interview was performed. RESULTS: A total of 211 patients underwent SM for HOCM. There was a bimodal age distribution related to sex; mean age for males and females was 46 ± 13 and 54 ± 14 years, respectively (p < 0.001). Functional New York Heart Association (NYHA) class improved significantly after surgery; 79% were in class III-IV preoperatively and 84% were in class I-II at follow-up (p < 0.001). Sixty percent had angina of Canadian Cardiovascular Society (CCS) grade III-IV preoperatively and 89% were in CCS I-II at follow-up (p < 0.001). There were significant improvements in resting left ventricular outflow tract gradient (64 ± 36 to 5 ± 5 mm Hg, p < 0.001), right ventricular systolic pressure (36 ± 7.3 to 32 ± 8 mm Hg, p < 0.001), left atrial size (4.6 ± 0.7 to 4.3 ± 0.6 cm, p < 0.001), and grade of mitral regurgitation (moderate to severe mitral regurgitation 28% to 3.5%, p < 0.001). In-hospital mortality was 0.5%, 1 year survival 98.6%, and 5-year survival 98.1%. Predictors of worse clinical outcomes were preoperative NYHA and CCS class III-IV (p < 0.001, p = 0.05), new onset atrial fibrillation (p < 0.001), and female sex (p = 0.03). CONCLUSIONS: Septal myectomy in patients with obstructive HOCM offers excellent symptom relief and minimal operative risk.

Recovery of left ventricular mechanics after transcatheter aortic valve implantation: effects of baseline ventricular function and postprocedural aortic regurgitation.

BACKGROUND: Impaired left ventricular (LV) myocardial deformation is associated with adverse outcome in patients with severe aortic stenosis (AS). The aim of this retrospective study was to assess the impact of transcatheter aortic valve implantation (TAVI) on the recovery of myocardial mechanics and the influence of postprocedural aortic regurgitation (AR). METHODS: Speckle-tracking echocardiography was used to assess multidirectional myocardial deformation (longitudinal and circumferential strain) and rotational mechanics (apical rotation and twist) before and at midterm follow-up after TAVI. Predictors of myocardial recovery, defined as a ≥20% relative increase in the magnitude of global longitudinal strain compared with baseline, were examined. RESULTS: Sixty-four patients (median age, 83 years; interquartile range, 77-86 years) with severe AS and high surgical risk (mean European System for Cardiac Operative Risk Evaluation score, 20 ± 13%) were evaluated. Overall, LV longitudinal deformation was impaired at baseline compared with controls. At 5 ± 3 months after TAVI, LV longitudinal deformation had significantly improved only in the group of patients with baseline LV ejection fractions (LVEF) ≤ 55%: global longitudinal strain from -9.7 ± 3.7% to -11.8 ± 3.2% (P = .05), longitudinal strain rate from -0.44 ± 0.14 sec(-1) to -0.57 ± 0.16 sec(-1) (P = .001), and early diastolic strain rate from 0.38 ± 0.17 sec(-1) to 0.49 ± 0.18 sec(-1) (P = .01). In patients with normal LVEFs, LV twist was supraphysiologic at baseline and normalized after TAVI (from 16.1 ± 6.9° to 11.9 ± 6.2°, P = .004). In patients with baseline LVEFs ≤ 55%, circumferential deformation was impaired before TAVI and improved after TAVI. Baseline LVEF (odds ratio, 0.56 per 10% increment; P = .02) and global longitudinal strain (odds ratio, 0.65 per absolute 1% increment; P < .001) were significant predictors of myocardial recovery. LV mass, volumes, and longitudinal strain failed to favorably remodel in patients with post-TAVI important AR (defined as new mild post-TAVI AR or moderate or severe post-TAVI AR [either preexisting or new AR]). CONCLUSIONS: TAVI restores LV function toward more physiologic myocardial mechanics in both normal- and depressed-LVEF groups. Patients with lower systolic function derive the most benefit in terms of longitudinal reverse remodeling. Postprocedural AR adversely affects LV structural and functional remodeling.

Use of myocardial strain imaging by echocardiography for the early detection of cardiotoxicity in patients during and after cancer chemotherapy: a systematic review.

The literature exploring the utility of advanced echocardiographic techniques (such as deformation imaging) in the diagnosis and prognostication of patients receiving potentially cardiotoxic cancer therapy has involved relatively small trials in the research setting. In this systematic review of the current literature, we describe echocardiographic myocardial deformation parameters in 1,504 patients during or after cancer chemotherapy for 3 clinically-relevant scenarios. The systematic review was performed following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines using the EMBASE (1974 to November 2013) and MEDLINE (1946 to November 2013) databases. All studies of early myocardial changes with chemotherapy demonstrate that alterations of myocardial deformation precede significant change in left ventricular ejection fraction (LVEF). Using tissue Doppler-based strain imaging, peak systolic longitudinal strain rate has most consistently detected early myocardial changes during therapy, whereas with speckle tracking echocardiography (STE), peak systolic global longitudinal strain (GLS) appears to be the best measure. A 10% to 15% early reduction in GLS by STE during therapy appears to be the most useful parameter for the prediction of cardiotoxicity, defined as a drop in LVEF or heart failure. In late survivors of cancer, measures of global radial and circumferential strain are consistently abnormal, even in the context of normal LVEF, but their clinical value in predicting subsequent ventricular dysfunction or heart failure has not been explored. Thus, this systematic review confirms the value of echocardiographic myocardial deformation parameters for the early detection of myocardial changes and prediction of cardiotoxicity in patients receiving cancer therapy.

The Ross procedure: outcomes at 20 years.

OBJECTIVES: Our study examines the outcomes of the Ross procedure in a cohort of 212 patients prospectively followed with clinical and echocardiographic assessments. METHODS: Patients' mean age was 34 ± 9 years; 66% were men and 82% had congenital aortic valve disease. The median follow-up was 13.8 years. Patients who had reoperations continued to be followed and entered into the survival analysis. RESULTS: There was 1 operative death as well as 9 late deaths (3 in patients who no longer had the Ross). Survival at 20 years was 93.6% and similar to the general population matched for age and sex. Fifteen patients required reoperations on the pulmonary autograft (4 repairs and 11 replacements), 8 on the pulmonary homograft, and 4 other cardiac procedures. At 20 years the freedom from reoperation on the pulmonary autograft was 81.8% and on the pulmonary homograft was 92.7%, and in both was 79.9%. Preoperative aortic insufficiency, aortic annulus diameter ≥15 mm/m(2), and being a man were associated with increased risk of reoperation on the pulmonary autograft. Twenty-six patients developed aortic insufficiency greater than mild and 25 patients developed pulmonary homograft dysfunction (defined as moderate or severe insufficiency and/or peak systolic gradient of >40 mm Hg). At 20 years the freedom from aortic insufficiency was 62.6% and freedom from pulmonary valve dysfunction was 53.5%. CONCLUSIONS: Survival after the Ross procedure in this cohort was similar to the general population. Dilated aortic annulus and aortic insufficiency were associated with increased risk of developing aortic insufficiency. Pulmonary homograft dysfunction was common at 20 years.

Subaortic right ventricular characteristics and relationship to exercise capacity in congenitally corrected transposition of the great arteries.

BACKGROUND: In congenitally corrected transposition of the great arteries (cc-TGA), the morphologic right ventricle acts as the subaortic (systemic) ventricle, and deterioration of the ventricle over time is a well-known complication. The objective of this study was to characterize the right ventricle and explore factors that may be contributing to ventricular dilation and dysfunction and the relationship with exercise capacity. METHODS: This was a prospective study of adults with cc-TGA. All patients underwent cardiopulmonary stress testing, ventricular volume and fibrosis assessment by cardiac magnetic resonance imaging, and Velocity Vector Imaging strain echocardiography. RESULTS: Twenty-six patients were included (mean age, 38 ± 16 years; 54% women). Exercise capacity was significantly reduced in patients with cc-TGA compared with normal subjects (20.9 ± 6.0 vs 30.8 ± 9.2 mL/kg/min, P = .001). The majority of patients (61%) had right ventricular (RV) ejection fractions ≤ 40%. There was no evidence of fibrosis on cardiac magnetic resonance imaging. There was a significant difference in diastolic volumes among those with RV ejection fractions > 40% versus ≤ 40% (173 ± 29mL vs 233 ± 65 mL, P = .02) and moderate or severe versus no or mild tricuspid regurgitation (240 ± 80mL vs 190 ± 38mL, P = .04). RV apical longitudinal and mid free wall circumferential strain was decreased compared with these values in controls. CONCLUSIONS: In this relatively "well" cc-TGA population, subaortic RV dilation, dysfunction, and exercise intolerance are a common problem. Significant systemic tricuspid atrioventricular valvular regurgitation is an important contributor to the problem. In this study, subaortic RV myocardial deformation parameters were found to be abnormal, suggesting that there is a failure of the ventricle to adapt to systemic pressures, and therapies to reduce afterload should be explored. Recurrent ischemia resulting in fibrosis likely does not contribute to RV dilation or dysfunction as demonstrated by the magnetic resonance imaging findings in this study.

Quantification of mitral valve anatomy by three-dimensional transesophageal echocardiography in mitral valve prolapse predicts surgical anatomy and the complexity of mitral valve repair.

BACKGROUND: Three-dimensional (3D) transesophageal echocardiography (TEE) is more accurate than two-dimensional (2D) TEE in the qualitative assessment of mitral valve (MV) prolapse (MVP). However, the accuracy of 3D TEE in quantifying MV anatomy is less well studied, and its clinical relevance for MV repair is unknown. METHODS: The number of prolapsed segments, leaflet heights, and annular dimensions were assessed using 2D and 3D TEE and compared with surgical measurements in 50 patients (mean age, 61 ± 11 years) who underwent MV repair for mainly advanced MVP. RESULTS: Three-dimensional TEE was more accurate (92%-100%) than 2D TEE (80%-96%) in identifying prolapsed segments. Three-dimensional TEE and intraoperative measurements of leaflet height did not differ significantly, while 2D TEE significantly overestimated the height of the posterior segment P1 and the anterior segment A2. Three-dimensional TEE quantitative MV measurements were related to surgical technique: patients with more complex MVP (one vs two to four vs five or more prolapsed segments) showed progressive enlargement of annular anteroposterior (31 ± 5 vs 34 ± 4 vs 37 ± 6 mm, respectively, P = .02) and commissural diameters (40 ± 6 vs 44 ± 5 vs 50 ± 10 mm, respectively, P = .04) and needed increasingly complex MV repair with larger annuloplasty bands (60 ± 13 vs 67 ± 9 vs 72 ± 10 mm, P = .02) and more neochordae (7 ± 3 vs 12 ± 5 vs 26 ± 6, P < .01). CONCLUSIONS: Measurements of MV anatomy on 3D TEE are accurate compared with surgical measurements. Quantitative MV characteristics, as assessed by 3D TEE, determined the complexity of MV repair.

Time to significant gradient reduction following septal balloon occlusion predicts the magnitude of final gradient response during alcohol septal ablation in patients with hypertrophic obstructive cardiomyopathy.

OBJECTIVES: The purpose of this study was to investigate whether a relationship exists between an acute reduction in resting left ventricular outflow tract (LVOT) gradient with balloon occlusion and the final invasive gradient response following alcohol septal ablation (ASA). BACKGROUND: ASA is an alternative therapy to myectomy surgery to reduce the basal septal thickness and decrease the resting and/or provocable LVOT gradient in patients with hypertrophic cardiomyopathy. Patients have a variable gradient response to occlusion of the septal perforator artery before ethanol infusion for ASA. METHODS: From November 1998 to November 2008, 120 patients (mean age 60 years [range 16 to 87 years], 50% women) with hypertrophic cardiomyopathy underwent ASA at our institution. The resting LVOT gradient (peak systolic left ventricle [LV] pressure - peak systolic aortic pressure) was measured continuously during the ASA procedure. The time to significant LVOT gradient decrease (defined as >50% decrease from baseline) was recorded following balloon occlusion of the dominant septal perforator coronary artery, which was found to perfuse the basal septum based on contrast echocardiographic studies. RESULTS: The mean baseline resting LVOT gradient was 86 ± 43 mm Hg, and it decreased to 17 ± 11 mm Hg following ASA (-80.2%). The mean time to significant gradient reduction was 3.6 ± 2 min (range 25 s to 11 min). The time to significant LVOT gradient reduction strongly correlated with the final magnitude of gradient reduction following ASA (r = -0.81, p < 0.001). CONCLUSIONS: This study demonstrates a correlation between the time to significant LVOT gradient reduction following septal perforator balloon occlusion and the magnitude of final gradient response after ASA.

When is the Ross operation a good option to treat aortic valve disease?

OBJECTIVE: We sought to identify suitable patients for the Ross operation. METHODS: A cohort of 212 patients (mean age, 34 + or - 9 years; 66% men; 82% with congenital aortic valve disease) underwent the Ross operation and was prospectively followed with clinical evaluations and echocardiographic analysis for 3.1 to 18 years (mean, 10.1 + or - 4.2 years). In addition to longitudinal outcomes determined by means of Kaplan-Meier analysis, Cox regression analysis was used to identify predictors of valve failure. RESULTS: There were 1 operative and 4 late deaths, none of which were valve related. Survival at 15 years was 96.6% + or - 1.5% and similar to that seen in the general population matched for age and sex. There were 20 reoperations: 13 in the pulmonary autograft, 3 in the pulmonary homograft, and 4 others. Freedom from reoperation in the pulmonary autograft at 15 years was 92.1% + or - 2.3%. Aortic insufficiency was the only independent predictor of reoperation. Freedom from moderate or severe aortic insufficiency at 15 years was 89.7%, and greater than mild aortic insufficiency was 63.2%. Male sex, aortic/pulmonary annular mismatch, aortic annulus of 27 mm or larger, and preoperative aortic insufficiency were associated with higher risk of late aortic insufficiency by means of log-rank analysis. Cox regression analysis identified male sex as the only independent predictor of postoperative aortic insufficiency. Freedom from moderate or severe pulmonary insufficiency, peak gradient of 40 mm Hg or greater, or both at 15 years was 70.8% + or - 6.8%, and event-free survival was 81% + or - 3.7%. CONCLUSIONS: The Ross operation provided suboptimal results in male patients with aortic insufficiency. The best outcomes were in female patients, those with aortic stenosis, and those with an aortic annulus of less than 27 mm in diameter.

Epiaortic scanning modifies planned intraoperative surgical management but not cerebral embolic load during coronary artery bypass surgery.

BACKGROUND: Patients with aortic atheroma are at increased risk for neurological injury after coronary artery bypass graft (CABG) surgery. We sought to determine the role of epiaortic ultrasound scanning for reducing cerebral embolic load, and whether its use leads to changes of planned intraoperative surgical management in patients undergoing CABG surgery. METHODS: Patients >70-yr-of-age scheduled for CABG surgery were prospectively randomized to either an epiaortic scanning (EAS) group (aortic manipulation guided by epiaortic ultrasound) or a control group (manual aortic palpation without EAS). All patients received a comprehensive transesophageal echocardiographic examination. Transcranial Doppler (TCD) was used to monitor the middle cerebral arteries for emboli continuously from 2 min before aortic cannulation to 2 min after aortic decannulation. Neurological assessment was performed with the National Institute of Health stroke scale before surgery and at hospital discharge. The NEECHAM confusion scale was used for assessment and monitoring of patient global cognitive function on each day after surgery until hospital discharge. RESULTS: Intraoperative surgical management was changed in 16 of 55 (29%) patients in the EAS group and in 7 of 58 (12%) patients in the control group (P = 0.025). These changes included adjustments of the ascending aorta cannulation site for cardiopulmonary bypass (CPB), the avoidance of aortic cross-clamping by using ventricular fibrillatory arrest during surgery, or by conversion to off-pump surgery. During surgery, 7 of 58 (12%) patients in the control group crossed over to the EAS group based on the results of manual aortic palpation. The median [range] TCD detected cerebral embolic count did not differ between the EAS and control groups during aortic manipulations (EAS, 11.5 [1-516] vs control, 22.0 [1-160], P = 0.91) or during CPB (EAS, 42.0 [4-516] vs control, 63.0 [5-758], P = 0.46). The NEECHAM confusion scores and National Institute of Health stroke scale scores were similar between the two groups. CONCLUSIONS: These results show that the use of EAS led to modifications in intraoperative surgical management in almost one-third of patients undergoing CABG surgery. The use of EAS did not lead to a reduced number of TCD-detected cerebral emboli before or during CPB.

Does myectomy convey survival benefit in hypertrophic cardiomyopathy?

Obstructive hypertrophic cardiomyopathy (HCM) can be treated by transaortic subaortic myectomy, which has been shown to improve patients' symptoms and abolish left ventricular outflow tract obstruction. Different options, such as dual chamber pacing and septal ethanol ablation, are now available for the management of obstructive HCM, and it is important to evaluate the risks and benefits of myectomy, especially its impact on survival. In this article, the authors review the clinical course of obstructive HCM and the early and long-term results of surgery. They examine the outcomes of obstructive HCM in patients after surgical versus conservative therapy. In addition, they review the studies that have compared other techniques to surgery for the management of obstructive HCM.

Mitral annular disjunction in advanced myxomatous mitral valve disease: echocardiographic detection and surgical correction.

Mitral annular disjunction is a structural abnormality of the mitral annulus fibrosus described by pathologists in association with mitral leaflet prolapse and defined as a separation between the atrial wall-mitral valve (MV) junction and the left ventricular attachment allowing for hypermobility of the MV apparatus. The transesophageal echocardiographic characteristics of this abnormality have not been previously described. In patients undergoing MV repair for myxomatous MV degeneration and evaluated using a standardized transesophageal echocardiographic protocol, annular disjunction (mean value 10 +/- 3 mm) was seen at the base of the posterior leaflet in 98% of patients with advanced, and in 9% of patients with mild/moderate MV degeneration. There was a significant correlation between the magnitude of disjunction and the number of segments with prolapse/flail (r = 0.397, P = .001). We found annular disjunction to be a common component of MV apparatus in advanced MV degeneration. Its recognition on transesophageal echocardiography is important to facilitate optimal MV repair. The modification of the repair technique allows surgical correction of the annular disjunction, which seems to optimize long-term results in these challenging cases.

Clinical and echocardiographic determinants of long-term survival after surgical myectomy in obstructive hypertrophic cardiomyopathy.

BACKGROUND: Surgical myectomy has been the standard treatment for patients with drug-refractory obstructive hypertrophic cardiomyopathy. The clinical and echocardiographic predictors of long-term survival and freedom from cardiovascular morbidity after myectomy have been unclear. METHODS AND RESULTS: We studied a consecutive cohort of 338 adult patients (age at operation 47+/-14 [range 18 to 77] years, 60% male) who underwent myectomy at our institution. Preoperative resting left ventricular outflow tract (LVOT) gradient was 66+/-32 mm Hg (range 5 to 158 mm Hg). Early postoperative mortality was 1.5% (5 deaths): 4 deaths occurred between 1978 and 1992, and 1 death occurred between 1993 and 2002. During long-term follow-up, 83% of patients reported an improvement to functional class I or II. The majority of patients (98%) had no resting LVOT gradient. Long-term survival was excellent, with 98+/-1% survival at 1 year, 95+/-1% at 5 years, and 83+/-3% at 10 years after myectomy. Multivariable Cox regression analysis identified 5 predictors of overall mortality: (1) age > or =50 years at surgery (hazard ratio [HR] 2.8, 95% CI 1.5 to 5.1, P=0.001), (2) female gender (HR 2.5, 95% CI 1.5 to 4.3, P=0.0009), (3) history of preoperative atrial fibrillation (HR 2.2, 95% CI 1.2 to 4.0, P=0.008), (4) concomitant CABG (HR 3.7, 95% CI 1.7 to 8.2, P=0.001), and (5) preoperative left atrial diameter > or =46 mm (HR 2.9, 95% CI 1.6 to 5.4, P=0.0008). Significant predictors of late major cardiovascular events found on multivariable analysis were (1) female gender (HR 3.3, 95% CI 2.0 to 5.4, P<0.0001), (2) history of preoperative atrial fibrillation (HR 1.9, 95% CI 1.1 to 3.3, P=0.02), and (3) preoperative left atrial diameter > or =46 mm (HR 2.5, 95% CI 1.5 to 4.3, P=0.0008). CONCLUSIONS: Myectomy provides excellent relief for LVOT obstruction in patients with hypertrophic cardiomyopathy. Preoperative clinical and echocardiographic variables can predict long-term outcome after myectomy.