Echocardiography Underestimates Stroke Volume and Aortic Valve Area: Implications for Patients With Small-Area Low-Gradient Aortic Stenosis

Background

Discordance between small aortic valve area (AVA; < 1.0 cm²) and low mean pressure gradient (MPG; < 40 mm Hg) affects a third of patients with moderate or severe aortic stenosis (AS). We hypothesized that this is largely due to inaccurate echocardiographic measurements of the left ventricular outflow tract area (LVOT_area) and stroke volume alongside inconsistencies in recommended thresholds.

Methods

One hundred thirty-three patients with mild to severe AS and 33 control individuals underwent comprehensive echocardiography and cardiovascular magnetic resonance imaging (MRI). Stroke volume and LVOT_area were calculated using echocardiography and MRI, and the effects on AVA estimation were assessed. The relationship between AVA and MPG measurements was then modelled with nonlinear regression and consistent thresholds for these parameters calculated. Finally the effect of these modified AVA measurements and novel thresholds on the number of patients with small-area low-gradient AS was investigated.

Results

Compared with MRI, echocardiography underestimated LVOT_area (n = 40; −0.7 cm²; 95% confidence interval [CI], −2.6 to 1.3), stroke volumes (−6.5 mL/m²; 95% CI, −28.9 to 16.0) and consequently, AVA (−0.23 cm²; 95% CI, −1.01 to 0.59). Moreover, an AVA of 1.0 cm² corresponded to MPG of 24 mm Hg based on echocardiographic measurements and 37 mm Hg after correction with MRI-derived stroke volumes. Based on conventional measures, 56 patients had discordant small-area low-gradient AS. Using MRI-derived stroke volumes and the revised thresholds, a 48% reduction in discordance was observed (n = 29).

Conclusions

Echocardiography underestimated LVOT_area, stroke volume, and therefore AVA, compared with MRI. The thresholds based on current guidelines were also inconsistent. In combination, these factors explain > 40% of patients with discordant small-area low-gradient AS.     

Overall survival is improved in mucinous adenocarcinoma of the colon

Introduction

Debate persists regarding the relationship between mucin expression and outcome in colon cancer. This arises due to discrepancy in the definition of mucinous adenocarcinoma and the combination of both colon and rectal cancers in analyses. This study examines the relationship between increased mucin production and outcomes in colon cancer.

Methods

Cases were classified according to the World Health Organization classification of mucinous adenocarcinoma of the colon. Accordingly, tumors were categorized as either (a) mucinous adenocarcinoma of the colon (greater than 50 % of the extracellular matrix occupied by mucin) or (b) non-mucinous adenocarcinoma of the colon. Overall survival and disease-free survival were calculated. A stepwise Cox proportional hazards regression model was employed to determine the risk of death/disease recurrence. Kaplan–Meier estimates of overall survival and disease-free survival were plotted for each group and compared using a log-rank test.

Results

On univariate analysis, mucinous adenocarcinoma was associated with reduced risk of death (P?=?0.01). On multivariate analysis, mucinous adenocarcinoma was also associated with reduced risk of death (hazard ratio (HR) 0.33, 95 % confidence interval (CI) 0.14–0.79, P?=?0.01). Kaplan–Meier estimates confirmed improved rate of survival in the mucinous vs. non-mucinous group (P?=?0.01). Mucinous adenocarcinoma did not affect disease-free survival (HR 0.75, 95 % CI 0.46–1.21, P?=?0.22). A comparison of Kaplan–Meier estimates for systemic recurrence demonstrated significant increases in systemic recurrence in the group with no mucin production (P?=?0.04) but not for locoregional recurrence (P?=?0.24).

Conclusions

Histopathological evidence of mucinous adenocarcinoma in colon cancer is associated with improved outcomes.     

Faculty Development to Enhance Humanistic Teaching and Role Modeling: A Collaborative Study at Eight Institutions

Background

There is increased emphasis on practicing humanism in medicine but explicit methods for faculty development in humanism are rare.

Objective

We sought to demonstrate improved faculty teaching and role modeling of humanistic and professional values by participants in a multi-institutional faculty development program as rated by their learners in clinical settings compared to contemporaneous controls.

Design

Blinded learners in clinical settings rated their clinical teachers, either participants or controls, on the previously validated 10-item Humanistic Teaching Practices Effectiveness (HTPE) questionnaire.

Participants

Groups of 7-9 participants at 8 academic medical centers completed an 18-month faculty development program. Participating faculty were chosen by program facilitators at each institution on the basis of being promising teachers, willing to participate in the longitudinal faculty development program.

Intervention

Our 18-month curriculum combined experiential learning of teaching skills with critical reflection using appreciative inquiry narratives about their experiences as teachers and other reflective discussions.

Main Measures

The main outcome was the aggregate score of the ten items on the questionnaire at all institutions.

Key Results

The aggregate score favored participants over controls (P = 0.019) independently of gender, experience on faculty, specialty area, and/or overall teaching skills.

Conclusions

Longitudinal, intensive faculty development that employs experiential learning and critical reflection likely enhances humanistic teaching and role modeling. Almost all participants completed the program. Results are generalizable to other schools.KEY WORDS: faculty development, attitudes and values, professionalism     

Endothelial function is associated with myocardial diastolic function in women with systemic lupus erythematosus

Endothelial dysfunction is associated with traditional and systemic lupus erythematosus (SLE)-specific risk factors, and early data suggest reversibility of endothelial dysfunction with therapy. The clinical relevance of endothelial function assessment has been limited by the lack of studies, demonstrating its prognostic significance and impact on early myocardial function. Therefore, we aimed to determine the association between endothelial and myocardial diastolic function in SLE women. Women with SLE and no coronary artery disease were prospectively recruited and underwent radionuclide myocardial perfusion imaging (MPI) (Jetstream, Philips, the Netherlands) to exclude subclinical myocardial ischemia. Cardiac and vascular functions were assessed in all patients (Alpha 10, Aloka, Tokyo). Diastolic function was assessed using pulse wave early (E) and late mitral blood inflow and myocardial tissue Doppler (mean of medial and lateral annulus e′) velocities. Endothelial function was measured using brachial artery flow-mediated vasodilatation (FMD%). Univariate and multivariate linear regressions were used to assess the association between FMD% and myocardial diastolic function, adjusting for potential confounders. Thirty-eight patients without detectable myocardial ischemia on MPI were studied (mean age 44 ± 10 years; mean disease duration 14 ± 6 years). About 61 % of patients had normal diastolic function (E/e′ ≤ 8), and 5 % of patients had definite diastolic dysfunction with E/e′ > 13 (mean 7.1 ± 2.9). FMD% was associated with E/e′ (regression coefficient β = ?0.35; 95 % CI ?0.62 to ?0.08; p = 0.01) independent of systolic blood pressure, age, and SLICC/ACR Damage Index.     

Ventricular interaction in a canine model of acute pulmonary hypertension and its modulation by vasoactive drugs

To determine the effect of a pulmonary glass bead embolism (GBE) upon left ventricular filling, we studied 13 dogs (seven with pericardium open, six with pericardium closed) before and after embolizing the pulmonary artery with sufficient glass beads to triple the pulmonary artery pressure. Furthermore, we examined the nature of the ventricular interaction and the effect upon hemodynamics created by intravenous nitroglycerin, dobutamine and hydralazine. Each dog was implanted with segment length crystals directed in the septal free wall plane of both ventricles, Millar catheters (Millar, Houston) placed in the right ventricle, left ventricle, and pulmonary artery (PA), and a thermodilution catheter placed in the PA. GBE reduced left ventricular end diastolic length (LVEDL) and stroke work, and shifted the left ventricular diastolic pressure-segment relationship (LVDPSR) upwards. The presence of a pericardium had little effect on the biventricular response to any of the test interventions. Nitroglycerin reduced right ventricular end diastolic length (RVEDL) and shifted the LVDPSR downwards. It did not increase LVEDL. Dobutamine increased left ventricular stroke work (LVSW) without altering LVEDL or the LVDPSR. Hydralazine did not change LVEDL, LVSW or shift LVDPSR. We conclude that GBE depresses left ventricular function by the Frank Starling mechanism and shifts the LVDPSR upwards. Because pericardiectomy die not prevent the decrease in LVEDL mediated by GBE, and nitroglycerin did not increase LVEDL despite decreasing RVEDL, a series interaction must dominate.     

Incidence and predictive value of congenital hypertrophy of retinal pigment epithelium in Chinese familial adenomatous polyposis patients.

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Right ventricular diastolic function after experimental right ventricular infarction: effects independent of the pericardium.

To determine if an isolated right ventricular wall infarct (RVI) alters right ventricular diastolic function (RVDF), 6 mongrel dogs were studied before and after a right ventricular wall infarct was produced by ligating the right coronary artery and embolizing the distal right coronary artery with mercury. Right ventricular diastolic function was assessed by prior instrumentation of the animals with an RV Millar catheter and segment length crystals attached to the infarct (I) and non-infarct (NI) territory of the right ventricle. The time constant of RV isovolumic relaxation (Tau) was assessed by fitting right ventricular pressure decline after minimum dp/dt to the equation 1nP = At + B, where A represents the slope of the relationship, a negative number, tau = -1/A. The right ventricular diastolic pressure segment length relationship (RVD PSR) was analyzed using a multiple linear regression model whereby the independent effects of heart rate, segment length, and right ventricular wall infarct could be assessed. Right ventricular wall infarct reduced stroke volume to 63% of baseline values largely by increases in RV-I end-systolic segment length. Tau was significantly prolonged. However, there was no significant upward shift in RVDPSR in any animal. These data suggest that in this model RV diastolic relaxation is impaired. However, the degree of this impairment is not significant enough to shift the right ventricular diastolic pressure segment length relationship, as long as the pericardium remains open.     

Expression of the C-erbB-3 protein in gastrointestinal tract tumours determined by monoclonal antibody RTJ1

We have examined the expression of the c-erbB-3 protein in a wide range of tumours of the gastrointestinal (GI) tract using immunocytochemical staining. Two antibodies were employed, a polyclonal antibody, 49.3, and a new monoclonal antibody, RTJ1, both raised to a synthetic peptide from the cytoplasmic domain of the human c-erbB-3 protein. The antibodies recognize c-erbB-3 by immunoprecipitation and Western blotting of lysate prepared from a cell line engineered to overexpress the protein. Both antibodies also detect expression of the protein in formalin-fixed, paraffin-embedded human tissues. The RTJ1 monoclonal antibody gave superior staining, showing lower background and more pronounced cell surface immunoreactivity. The c-erbB-3 protein was found in normal epithelial cells throughout the GI tract, in squamous epithelium of the oropharanyx and oesophagus, in the parietal cells of the stomach, and in the surface enterocytes of the small and large bowel. Seventy-six tumours arising at these sites were examined for c-erbB-3 protein expression. Widely varying levels of expression were seen, from absent to intense staining with cell membrane accentuation.     

Right ventricular pressure overload during acute lung injury: Cardiac mechanics and the pathophysiology of right ventricular systolic dysfunction

Right ventricular (RV) pressure overload (PO) accompanying acute lung injury is associated with a poor prognosis. To determine if RV ischemia (RVI) is responsible for RV failure (RVF) during acute PO induced by an acute lung injury, a group of eight dogs was studied with the pericardia open after instrumentation with RV, left ventricular (LV), and pulmonary artery (PA) Millar catheters, a PA thermodilution catheter, an aortic fluid-filled catheter, and RV and LV septal-free wall segment length crystals. The animals were studied during baseline, and after infusing glass beads into the right atrium sufficient to first double the PA pressure (PAP), then triple the PAP, and finally to produce RVF (decreased cardiac output with increased RV preload). Transmural RV biopsies were obtained at each phase for adenosine triphosphate and creatine phosphate (CP) assays. To determine the mechanism of RVI, a second group of nine dogs was studied (with the pericardia closed) at baseline, after a doubling of PAP and during RVF. Right ventricular myocardial blood flow was determined by a microsphere technique at each phase and was correlated with the determinants of RV myocardial O₂ demand and supply. In the open pericardia group, RVF, but not doubling or tripling of PAP, was associated with a decrease in CP to 50% of baseline conditions, confirming RVI (4.82 ± 3.67 versus 10.39 ± 3.94 μmol/gm wet weight; P < .005). In the closed pericardia group, RV myocardial blood flow increased in response to myocardial O₂ demands (multiple R = .69 for endocardial and .64 for epicardial flow; P < .05), although the ratio for total RV blood flow to myocardial O₂ demand ratio (planimetered area beneath RV pressure tracing) decreased (4.88 ± 2.76 versus 2.08 ± 2.14; P < .05). In both groups of dogs, RVF was associated with a similar decrease in LV end diastolic segment length or preload (17% in open group and 10% in closed group; P = NS between groups) and stroke work. From these observations, we conclude that after an acute lung injury, RVPO induces RVF because RV myocardial O₂ demand outstrips RV myocardial O₂ supply. Coincidentally with RVF, LV function is depressed on a preload-mediated basis independent of the pericardium, suggesting a dominant “series” interaction between both ventricles. These observations suggest that therapy in patients with acute lung injury is better aimed at increasing RV myocardial blood flow and RV function.