James W. Tam

Effect of Lipid Lowering With Rosuvastatin on Progression of Aortic Stenosis Results of the Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin (ASTRONOMER) Trial

Background— Aortic stenosis (AS) is an active process with similarities to atherosclerosis. The objective of this study was to assess the effect of cholesterol lowering with rosuvastatin on the progression of AS. Methods and Results— This was a randomized, double-blind, placebo-controlled trial in asymptomatic patients with mild to moderate AS and no clinical indications for cholesterol lowering. The patients were randomized to receive either placebo or rosuvastatin 40 mg daily. A total of 269 patients were randomized: 134 patients to rosuvastatin 40 mg daily and 135 patients to placebo. Annual echocardiograms were performed to assess AS progression, which was the primary outcome; the median follow-up was 3.5 years. The peak AS gradient increased in patients receiving rosuvastatin from a baseline of 40.8±11.1 to 57.8±22.7 mm Hg at the end of follow-up and in patients with placebo from 41.6±10.9 mm Hg at baseline to 54.8±19.8 mm Hg at the end of follow-up. The annualized increase in the peak AS gradient was 6.3±6.9 mm Hg in the rosuvastatin group and 6.1±8.2 mm Hg in the placebo group (P=0.83). Treatment with rosuvastatin was not associated with a reduction in AS progression in any of the predefined subgroups. Conclusion— Cholesterol lowering with rosuvastatin 40 mg did not reduce the progression of AS in patients with mild to moderate AS; thus, statins should not be used for the sole purpose of reducing the progression of AS. Clinical Trial Registration Information— URL: http://www.controlled-trials.com/. Clinical trial registration number: ISRCTN 32424163.

Oxidized Phospholipids, Lipoprotein(a), and Progression of Calcific Aortic Valve Stenosis

BACKGROUND Elevated lipoprotein(a) (Lp[a]) is associated with aortic stenosis (AS). Oxidized phospholipids (OxPL) are key mediators of calcification in valvular cells and are carried by Lp(a). OBJECTIVES This study sought to determine whether Lp(a) and OxPL are associated with hemodynamic progression of AS and AS-related events. METHODS OxPL on apolipoprotein B-100 (OxPL-apoB), which reflects the biological activity of Lp(a), and Lp(a) levels were measured in 220 patients with mild-to-moderate AS. The primary endpoint was the progression rate of AS, measured by the annualized increase in peak aortic jet velocity in m/s/year by Doppler echocardiography; the secondary endpoint was need for aortic valve replacement and cardiac death during 3.5 ± 1.2 years of follow-up. RESULTS AS progression was faster in patients in the top tertiles of Lp(a) (peak aortic jet velocity: +0.26 ± 0.26 vs. +0.17 ± 0.21 m/s/year; p = 0.005) and OxPL-apoB (+0.26 ± 0.26 m/s/year vs. +0.17 ± 0.21 m/s/year; p = 0.01). After multivariable adjustment, elevated Lp(a) or OxPL-apoB levels remained independent predictors of faster AS progression. After adjustment for age, sex, and baseline AS severity, patients in the top tertile of Lp(a) or OxPL-apoB had increased risk of aortic valve replacement and cardiac death. CONCLUSIONS Elevated Lp(a) and OxPL-apoB levels are associated with faster AS progression and need for aortic valve replacement. These findings support the hypothesis that Lp(a) mediates AS progression through its associated OxPL and provide a rationale for randomized trials of Lp(a)-lowering and OxPL-apoB-lowering therapies in AS. (Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin [ASTRONOMER]; NCT00800800).

Metabolic syndrome is associated with more pronounced impairment of left ventricle geometry and function in patients with calcific aortic stenosis: a substudy of the ASTRONOMER (Aortic Stenosis Progression Observation Measuring Effects of Rosuvastatin).

OBJECTIVES The aim of this study was to examine the relationship between metabolic syndrome (MetS) and left ventricular (LV) geometry and function in patients with asymptomatic aortic stenosis (AS). BACKGROUND Recent experimental studies reveal that, among animals with sustained pressure overload, those with insulin resistance induced by a high-carbohydrate/high-fat diet have more severe LV hypertrophy and dysfunction compared to animals fed with standard diet. METHODS Among the 272 patients who were recruited in the ASTRONOMER (Aortic Stenosis Progression Observation Measuring Effects of Rosuvastatin) study, none had hypercholesterolemia, diabetes mellitus, or coronary artery disease (exclusion criteria) at baseline. However, 33% had systemic hypertension and 27% had MetS as identified by the National Cholesterol Education Program, Adult Treatment Panel III, clinical criteria. RESULTS Patients with MetS had higher LV mass index (53 +/- 14 g/m(2.7) vs. 47 +/- 15 g/m(2.7); p = 0.002), relative wall thickness ratio (0.47 +/- 0.09 vs. 0.42 +/- 0.09; p = 0.001), and prevalence of LV concentric hypertrophy (42% vs. 23%) and lower peak early diastolic (8.2 +/- 2.4 cm/s vs. 9.6 +/- 3.1 cm/s, p = 0.001) and peak systolic (7.9 +/- 1.7 cm/s vs. 8.7 +/- 2.2 cm/s, p = 0.009) mitral annular myocardial velocities compared to patients without MetS. After adjustment for age, sex, low-density lipoprotein cholesterol, hypertension, and valvuloarterial impedance (i.e., global LV hemodynamic load), MetS was independently associated with higher relative wall thickness ratio (p = 0.01), higher prevalence of concentric hypertrophy (p = 0.03), and reduced diastolic (p = 0.01) and systolic (p = 0.03) myocardial velocities. CONCLUSIONS Notwithstanding AS severity and increase in hemodynamic load, MetS is independently associated with more pronounced LV concentric hypertrophy and worse myocardial function in patients with AS, which may, in turn, predispose them to the occurrence of adverse events. (Effects of Rosuvastatin on Aortic Stenosis Progression [ASTRONOMER]; NCT00800800).

Impact of Metabolic Syndrome on Progression of Aortic Stenosis Influence of Age and Statin Therapy

OBJECTIVES The aims of this study were to examine prospectively the relationship between metabolic syndrome (MetS) and aortic stenosis (AS) progression and to evaluate the effect of age and statin therapy on AS progression in patients with or without MetS. BACKGROUND Despite the clear benefits of statin therapy in primary and secondary coronary heart disease prevention, several recent randomized trials have failed to demonstrate any significant effect of this class of drugs on the progression of AS. Previous retrospective studies have reported an association between MetS and faster AS progression. METHODS This predefined substudy included 243 of the 269 patients enrolled in the ASTRONOMER (AS Progression Observation: Measuring Effects of Rosuvastatin) trial. Follow-up was 3.4 ± 1.3 years. AS progression rate was measured by calculating the annualized increase in peak aortic jet velocity measured by Doppler echocardiography. RESULTS Patients with MetS (27%) had faster stenosis progression (+0.25 ± 0.21 m/s/year vs. +0.19 ± 0.19 m/s/year, p = 0.03). Predictors of faster AS progression in multivariate analysis were older age (p = 0.01), higher degree of valve calcification (p = 0.01), higher peak aortic jet velocity at baseline (p = 0.007), and MetS (p = 0.005). Impact of MetS on AS progression was most significant in younger (< 57 years) patients (MetS: +0.24 ± 0.19 m/s/year vs. no MetS: +0.13 ± 0.18 m/s/year, p = 0.008) and among patients receiving statin therapy (+0.27 ± 0.23 m/s/year vs. +0.19 ± 0.18 m/s/year, p = 0.045). In multivariate analysis, the MetS-age interaction was significant (p = 0.01), but the MetS-statin use interaction was not. CONCLUSIONS MetS was found to be a powerful and independent predictor of faster AS progression, with more pronounced impact in younger patients. These findings emphasize the importance of routinely identifying and treating MetS in AS patients. The apparent faster stenosis progression in the subset of normocholesterolemic patients with MetS receiving the statin will need to be confirmed by future studies.

Clinical ResearchValve DiseaseImpact of Metabolic Syndrome on Progression of Aortic Stenosis: Influence of Age and Statin Therapy

OBJECTIVES The aims of this study were to examine prospectively the relationship between metabolic syndrome (MetS) and aortic stenosis (AS) progression and to evaluate the effect of age and statin therapy on AS progression in patients with or without MetS. BACKGROUND Despite the clear benefits of statin therapy in primary and secondary coronary heart disease prevention, several recent randomized trials have failed to demonstrate any significant effect of this class of drugs on the progression of AS. Previous retrospective studies have reported an association between MetS and faster AS progression. METHODS This predefined substudy included 243 of the 269 patients enrolled in the ASTRONOMER (AS Progression Observation: Measuring Effects of Rosuvastatin) trial. Follow-up was 3.4 ± 1.3 years. AS progression rate was measured by calculating the annualized increase in peak aortic jet velocity measured by Doppler echocardiography. RESULTS Patients with MetS (27%) had faster stenosis progression (+0.25 ± 0.21 m/s/year vs. +0.19 ± 0.19 m/s/year, p = 0.03). Predictors of faster AS progression in multivariate analysis were older age (p = 0.01), higher degree of valve calcification (p = 0.01), higher peak aortic jet velocity at baseline (p = 0.007), and MetS (p = 0.005). Impact of MetS on AS progression was most significant in younger (< 57 years) patients (MetS: +0.24 ± 0.19 m/s/year vs. no MetS: +0.13 ± 0.18 m/s/year, p = 0.008) and among patients receiving statin therapy (+0.27 ± 0.23 m/s/year vs. +0.19 ± 0.18 m/s/year, p = 0.045). In multivariate analysis, the MetS-age interaction was significant (p = 0.01), but the MetS-statin use interaction was not. CONCLUSIONS MetS was found to be a powerful and independent predictor of faster AS progression, with more pronounced impact in younger patients. These findings emphasize the importance of routinely identifying and treating MetS in AS patients. The apparent faster stenosis progression in the subset of normocholesterolemic patients with MetS receiving the statin will need to be confirmed by future studies.

Development and Evaluation of Methodologies for Teaching Focused Cardiac Ultrasound Skills to Medical Students

BACKGROUND Handheld ultrasound is emerging as an important tool for point-of-care cardiac assessment. Although cardiac ultrasound skills are traditionally introduced during postgraduate training, the optimal time and methodology to initiate training in focused cardiac ultrasound (FCU) are unknown. The objective of this study was to develop and evaluate a novel curriculum for training medical students in the use of FCU. METHODS The study was conducted in two phases. In the first phase, 12 first-year medical students underwent FCU training over an 8-week period. In the second phase, 45 third-year medical students were randomized to one of three educational programs. Program 1 consisted of a lecture-based approach with scan training by a sonographer. Program 2 coupled electronic education modules with sonographer scan training. Program 3 was fully self-directed, combining electronic modules with scan training on a high-fidelity ultrasound simulator. Image interpretation skills and scanning technique were evaluated after each program. RESULTS First-year medical students were able to modestly improve interpretation ability and acquire limited scanning skills. Third-year medical students exhibited similar improvement in mean examination score for image interpretation whether a lecture-based program or electronic modules was used. Students in the self-directed group using an ultrasound simulator had significantly lower mean quality scores than students taught by sonographers. CONCLUSIONS Third-year medical students were able to acquire FCU image acquisition and interpretation skills after a novel training program. Self-directed electronic modules are effective for teaching introductory FCU interpretation skills, while expert-guided training is important for developing scanning technique.

The ability to achieve complete revascularization is associated with improved in-hospital survival in cardiogenic shock due to myocardial infarction: Manitoba cardiogenic SHOCK Registry investigators.

Objectives: To identify predictors of survival in a retrospective multicentre cohort of patients with cardiogenic shock undergoing coronary angiography and to address whether complete revascularization is associated with improved survival in this cohort. Background: Early revascularization is the standard of care for cardiogenic shock. Coronary bypass grafting and percutaneous intervention have complimentary roles in achieving this revascularization. Methods: A total of 210 consecutive patients (mean age 66 ± 12 years) at two tertiary centres from 2002 to 2006 inclusive with a diagnosis of cardiogenic shock were evaluated. Univariate and multivariate predictors of in‐hospital survival were identified utilizing logistic regression. Results: ST elevation infarction occurred in 67% of patients. Thrombolysis was administered in 34%, PCI was attempted in 62% (88% stented, 76% TIMI 3 flow), CABG was performed in 22% (2.7 grafts, 14 valve procedures), and medical therapy alone was administered to the remainder. The overall survival to discharge was 59% (CABG 68%, PCI 57%, medical 48%). Independent predictors of mortality included complete revascularization (P = 0.013, OR = 0.26 (95% CI: 0.09–0.76), hyperlactatemia (P = 0.046, OR = 1.14 (95% CI: 1.002–1.3) per mmol increase), baseline renal insufficiency (P = 0.043, OR = 3.45, (95% CI: 1.04–11.4), and the presence of anoxic brain injury (P = 0.008, OR = 8.22 (95% CI: 1.73–39.1). Within the STEMI with concomitant multivessel coronary disease subgroup of this population (N = 101), independent predictors of survival to discharge included complete revascularization (P = 0.03, OR = 2.5 (95% CI: 1.1–6.2)) and peak lactate (P = 0.02). Conclusions: The ability to achieve complete revascularization may be strongly associated with improved in‐hospital survival in patients with cardiogenic shock.

Nineteen-millimeter prosthetic aortic valves allow normalization of left ventricular mass in elderly women.

BACKGROUND Implantation of small aortic valve prostheses has been reported to be associated with impaired left ventricular (LV) mass regression and incomplete resolution of symptoms although these data have been generated largely with male patients. Therefore we sought to determine the clinical and hemodynamic outcomes of female patients who received a 19-mm aortic valve. METHODS Between May 1995 and December 2000, 38 female patients (average age 73 years, range 42 to 89) underwent isolated aortic valve replacement (AVR; n = 22) or AVR plus coronary artery bypass graft surgery (CABG; n = 16) with a 19-mm aortic prosthesis. The average New York Heart Association (NYHA) class was 3.08 and of the 26 patients who had angina, 47.2% were in CCS class III or IV. Clinical and echocardiographic follow-up was done an average of 33.4 months (8 to 72) after surgery. RESULTS Operative mortality was 10.5%. Overall survival at an average of 33 months was 71.1%. The average NYHA class was 1.52 +/- 0.34 postoperatively (p < 0.001 versus preoperative) and 95% had no anginal symptoms or were in Canadian Cardiovascular Society class I. The LV mass index showed significant regression (114 +/- 11 g/m2 to 89 +/- 9 g/m2, p = 0.001) despite an effective orifice area index (EOAI) of 0.64 +/- 0.09 cm2/m2. CONCLUSIONS Despite a very small EOAI, elderly female patients with 19-mm prosthetic aortic valves can experience a satisfactory improvement in symptoms and normalization of LV mass. This finding suggests that small prosthetic aortic valves continue to have an application in contemporary cardiac surgical practice. The current perception of patient-prosthesis mismatch may need to be reconsidered for select populations.

What Is the Real Clinical Utility of Echocardiography? A Prospective Observational Study

This was a prospective, structured interview to evaluate physician expectations of echocardiography and the subsequent impact on patient care. The setting involved requests for echocardiograms in patients admitted to a tertiary care teaching hospital. Measurements included assessment of the diagnostic and therapeutic implications of echocardiography perceived by the physicians and subsequently reported and confirmed by blinded chart review. From January to May 1997, 542 echocardiograms were performed on 500 inpatients (age 62 +/- 17 years; 56% men). Referring physicians were mainly house staff (83%) and from medical services. The main indications were evaluation of left ventricular function (54%) or valve function (16%). At the time of the request, 89% of physicians believed that echocardiography was needed to guide future investigations or treatment, although in 24% of cases, physicians could not provide details of such. A reported change in treatment occurred in 57% and was validated by chart review in 38%. Changes occurred more frequently in patients in the intensive care unit versus those not in the intensive care unit (54% vs 37%, P =.02) but were similar between attending physicians and house staff (frequency of change 41% vs 39%, P = not significant) and between those with and those without previous echocardiograms (38% vs 39%, P = not significant). The utility of the echocardiogram to influence treatment decisions in hospitalized patients is high, especially in critically ill patients. However, this impact is less than is anticipated at the time of the initial request. Further studies involving more select populations of patients are required.

Structure and process measures of quality of care in adult congenital heart disease patients: A pan-Canadian study

BACKGROUND There are more adults than children with congenital heart disease. Of over 96,000 ACHD patients in Canada, approximately 50% require ongoing expert care. In spite of published recommendations, data on the quality of care for ACHD patients are lacking. METHODS Survey methodology targeted all Canadian Adult Congenital Heart (CACH) network affiliated ACHD centers. Clinics were asked to prospectively collect outpatient and procedural volumes for 2007. In 2008, centers were surveyed regarding infrastructure, staffing, patient volumes and waiting times. RESULTS All 15 CACH network registered centers responded. The total number of patients followed in ACHD clinics was 21,879 (median per clinic=1132 (IQR: 585, 1816)). Of the total 80 adult and pediatric cardiologists affiliated to an ACHD clinic, only 27% had received formal ACHD training. Waiting times for non-urgent consultations were 4 ± 2 months, and 4 ± 3 months for percutaneous and surgical procedures. These were beyond Canadian recommended targets at 11 sites (73%) for non-urgent consultations, at 8 sites (53%) for percutaneous interventions and 13 sites (87%) for surgery. CONCLUSIONS Of a minimum number of 96,000 ACHD patients in Canada, only 21,879 were being regularly followed in 2007. At most sites waiting times for ACHD services were beyond Canadian recommended targets. In spite of universal health care access, published guidelines for ACHD patient structure and process measures of health care quality are not being met.