Effect of Regional Upper Septal Hypertrophy on Echocardiographic Assessment of Left Ventricular Mass and Remodeling in Aortic Stenosis.

BACKGROUND: Transthoracic echocardiography (TTE) is the reference method for evaluation of aortic stenosis (AS), and it is extensively used to quantitate left ventricular (LV) mass and volumes. Regional upper septal hypertrophy (USH) or septal bulge is a frequent finding in patients with AS and may lead to overestimation of LV mass when using linear measurements. The objective of this study was to compare estimates of LV mass obtained by two-dimensional transthoracic echocardiographic LV dimensions measured at different levels of the LV cavity with those obtained by cardiovascular magnetic resonance (CMR). METHODS: One hundred six patients (mean age, 63 ± 15 years; 68% men) with AS were included in this subanalysis of the PROGRESSA study. Two-dimensional transthoracic echocardiographic measurements of LV dimensions were obtained at the basal level (BL; as recommended in guidelines), immediately below the septal bulge (BSB), and at a midventricular level (ML). Regional USH was defined as a basal interventricular septal thickness ≥ 13 mm and >1.3 times the thickness of the septal wall at the ML. Agreement between transthoracic echocardiographic and CMR measures was evaluated using Bland-Altman analysis. RESULTS: The distribution of AS severity was mild in 23%, moderate in 57%, and severe in 20% of patients. Regional USH was present in 28 patients (26%). In the whole cohort, two-dimensional TTE overestimated LV mass (bias: BL, +60 ± 31 g; BSB, +59 ± 32 g; ML, +54 ± 32 g; P = .02). The biplane Simpson method slightly but significantly underestimated LV end-diastolic volume (bias -10 ± 20 mL, P < .001) compared with CMR. Overestimation of LV mass was more marked in patients with USH when measuring at the BL and was significantly lower when measuring LV dimensions at the ML (P < .025 vs BL and BSB). CONCLUSIONS: Two-dimensional TTE systematically overestimated LV mass and underestimated LV volumes compared with CMR. However, the bias between TTE and CMR was less important when measuring at the ML. Measurements at the BL as suggested in guidelines should be avoided, and measurements at the ML should be preferred in patients with AS, especially in those with USH.

Sex-Related Differences in the Extent of Myocardial Fibrosis in Patients With Aortic Valve Stenosis.

OBJECTIVES: The aim of this study was to assess the effect of sex on myocardial fibrosis as assessed by using cardiac magnetic resonance (CMR) imaging in aortic stenosis (AS). BACKGROUND: Previous studies reported sex-related differences in the left ventricular (LV) remodeling response to pressure overload in AS. However, there are very few data regarding the effect of sex on myocardial fibrosis, a key marker of LV decompensation and adverse cardiac events in AS. METHODS: A total of 249 patients (mean age 66 ± 13 years; 30% women) with at least mild AS were recruited from 2 prospective observational cohort studies and underwent comprehensive Doppler echocardiography and CMR examinations. On CMR, T1 mapping was used to quantify extracellular volume (ECV) fraction as a marker of diffuse fibrosis, and late gadolinium enhancement (LGE) was used to assess focal fibrosis. RESULTS: There was no difference in age between women and men (age 66 ± 15 years vs 66 ± 12 years; p = 0.78). However, women presented with a better cardiovascular risk profile than men with less hypertension, dyslipidemia, diabetes, and coronary artery disease (all, p ≤ 0.10). As expected, LV mass index measured by CMR imaging was smaller in women than in men (p < 0.0001). Despite fewer comorbidities, women presented with larger ECV fraction (median: 29.0% [25th to 75th percentiles: 27.4% to 30.6%] vs. 26.8% [25th to 75th percentiles: 25.1% to 28.7%]; p < 0.0001) and similar LGE (median: 4.5% [25th-75th percentiles: 2.3% to 7.0%] vs. 2.8% [25th-75th percentiles: 0.6% to 6.8%]; p = 0.20) than men. In multivariable analysis, female sex remained an independent determinant of higher ECV fraction and LGE (all, p ≤ 0.05). CONCLUSIONS: Women have greater diffuse and focal myocardial fibrosis independent of the degree of AS severity. These findings further emphasize the sex-related differences in LV remodeling response to pressure overload.

Randomized trial of a smoking cessation intervention in hospitalized patients.

A hospitalization is a time when perceived vulnerability to dangers from smoking and quitting motivation may be at their peak. Aim was to determine whether a smoking cessation intervention of moderate intensity would increase the smoking cessation rate in hospitalized smokers. Design was randomized trial, conducted in a university-affiliated cardio-pulmonary tertiary care center. Participants were hospitalized smokers aged < or =70 years. Intervention was a smoking cessation intervention consisting of education and psychological support, with or without pharmacological therapy, associated with follow-up phone calls. Patients assigned to the control group received usual care. Measurement was point prevalence cessation rate at 1-year follow-up. A total of 468 patients were screened; 196 were randomized. Although the smoking cessation rates at 12-month follow-up were higher than expected, we found no significant difference between the study groups (intervention: 30.3%; control: 27.8%). Similar results were obtained in patients whose smoking status was validated by urinary cotinine assay. Length of stay and dependence to nicotine were the only significant predictors of smoking cessation. A smoking cessation intervention of moderate intensity delivered in a tertiary cardio-pulmonary center did not increase the smoking cessation rate at 1-year follow-up. The results of this trial should not divert those who deliver care to inpatients from delivering a brief smoking cessation intervention.

A convenient five-drug cocktail for the assessment of major drug metabolizing enzymes: a pilot study.

AIMS: To assess the feasibility of administering at the same time low doses of five probe drugs, metoprolol (25 mg), chlorzoxazone (250 mg), tolbutamide (250 mg), dapsone (100 mg) and caffeine (100 mg) to determine simultaneously the activities of CYP2D6, CYP2E1, CYP2C9, CYP3A4, CYP1A2, N-acetyltransferase-2 and xanthine oxidase. METHODS: Ten healthy young non-smoking males received the following drugs or combinations of drugs over a 5-week period: week 1) metoprolol; 2) tolbutamide; 3) caffeine, chlorzoxazone and dapsone; 4) caffeine, chlorzoxazone, dapsone and metoprolol; 5) caffeine, chlorzoxazone, dapsone, metoprolol and tolbutamide. The drugs were self-administered at bedtime and urine was collected for the following 8 h. RESULTS: Mean molar phenotypic ratios obtained after administering metoprolol (mean change of -11%) or tolbutamide (mean change of -0.3%) alone, were not significantly different from those obtained when other drugs were co-administered (P > 0.05). The mean within-subject coefficients of variation were 33%, 18%, 22%, 13%, 16%, 13% and 5% for CYP3A4, CYP2D6, CYP2C9, CYP2E1, CYP1A2, N-acetyltransferase 2 and xanthine oxidase metabolic ratios, respectively. No significant interactions (P > 0.5) were observed during the simultaneous administration of various combinations of the five probe drugs. CONCLUSIONS: We propose that this cocktail, composed of five widely available drugs, constitutes a promising means of simultaneously determining the activities of the major CYP enzymes in large populations.

Left ventricular shape assessment: a new simple diagnostic tool in stress echocardiography.

OBJECTIVE: Knowing that ventricular shape can be distorted by ischemia, we conducted this retrospective study to evaluate the value of left ventricular shape assessment as a diagnostic tool in stress echocardiography. METHODS: Forty studies (normal and abnormal dobutamine or exercise tests) were analyzed. All patients had normal systolic function at baseline. Endocardial borders were traced in diastole, in systole, at rest, and at peak stress. The endocardial border tracings (without corresponding video images) were presented to a blinded observer. Normal shape was defined as "rectangular or circular in parasternal long- and short-axis views, respectively, and triangular in the apical view." On the basis of those simple criteria for normal ventricular shape, the tracings were classified as normal or abnormal (ischemia) and results were compared with the wall-motion analysis of video images. RESULTS: Sensitivity, specificity, and positive and negative predictive values for shape abnormalities were 95%. Thirty-eight of the 40 studies were accurately classified without looking at the video tapes of the studies. CONCLUSIONS: Visual evaluation of ventricular shape can be very helpful in stress echocardiography. It can be easily accomplished even by someone with limited experience in this technique.

Economic impact of contrast stress echocardiography on the diagnosis and initial treatment of patients with suspected coronary artery disease.

OBJECTIVE: To estimate the impact of contrast stress echocardiography on resource use in the treatment of patients with suspected coronary artery disease (CAD). METHODS: Fifty-nine patients with suspected CAD underwent nuclear perfusion imaging and contrast echocardiography examination. Further treatment was planned after each test and a final treatment was recommended after reviewing the results of both examinations. Medical resources and productivity losses were then collected for a 3-month follow-up period. RESULTS: Diagnosis was possible in 96.6% of patients with nuclear perfusion imaging and 93.2% with contrast echocardiography, resulting in a cost per successful diagnosis of $637 (Can) and $476 (Can), respectively. For the majority of patients (74%), both tests provided the same result, but for 12 patients nuclear imaging suggested abnormal perfusion, whereas contrast echocardiography indicated normal function and for 2 patients it was the opposite situation. Per-patient costs for the total patient population decreased from $316 (Can) after nuclear perfusion imaging to $250 (Can) when results from both tests were known. Three-month follow-up societal costs were $441 (Can) per patient, with hospitalization contributing 58% of this total cost. CONCLUSION: Contrast echocardiography has a similar success rate to nuclear perfusion imaging in diagnosing CAD, but has a 28% lower cost and has the potential of additional cost savings through the elimination of further diagnostic tests.