Charles R. Cannan

Echocardiographic Assessment of Commissural Calcium: A Simple Predictor of Outcome After Percutaneous Mitral Balloon Valvotomy

OBJECTIVES This study was undertaken to determine whether the presence of calcium in the mitral valve commissures, as demonstrated echocardiographically, could predict outcome and to compare this with an established echocardiographic scoring system. BACKGROUND Percutaneous mitral balloon valvotomy is an effective form of treatment for mitral valve stenosis. It is important to identify patients who would benefit from this procedure. Commissural splitting is the dominant mechanism by which mitral valve stenosis is relieved by this technique, and thus commissural morphology may predict outcome. METHODS One hundred forty-nine consecutive patients who underwent percutaneous mitral balloon valvotomy at the Mayo Clinic were evaluated retrospectively. The morphology of the mitral valve apparatus on the baseline echocardiograms was scored in blinded manner using a semiquantitative grading system of leaflet thickening, mobility, calcification and subvalvular thickening (Abascal score). Additionally, each of the medial and lateral commissures was graded for the presence or absence of calcification. End points were death, New York Heart Association functional class, repeat percutaneous mitral balloon valvotomy and mitral valve replacement at follow-up. RESULTS The mean follow-up period was 1.8 years (maximum 7.9 years). Univariate predictors of death and all events combined included age, the use of a double-balloon technique, the presence of calcium in a commissure and the Abascal score, as continuous variables. Patients with an Abascal score < or = 8 showed a trend toward improved survival at 36 months free of death, repeat percutaneous mitral balloon valvotomy or mitral valve replacement (78 +/- 6% vs. 67 +/- 8%, p = 0.07) and free of all events combined (75 +/- 6% vs. 64 +/- 8%, p = 0.07) versus those patients with a score > 8. However, survival at 36 months free of death, repeat percutaneous mitral balloon valvotomy or mitral valve replacement (86 +/- 4% vs. 40 +/- 4%) and free of all events combined (82 +/- 5% vs. 38 +/- 10%) at follow-up was significantly different between patients without commissural calcium and those with commissural calcium (p < 0.001). In a Cox regression model with Abascal score and commissural calcium and their interaction, calcification emerged as the only significant variable (p < 0.01). CONCLUSIONS The presence of commissural calcium is a strong predictor of outcome after percutaneous mitral balloon valvotomy. Patients with evidence of calcium in a commissure have a lower survival rate and a higher incidence of mitral valve replacement and all end points combined. Thus, the simple presence or absence of commissural calcification assessed by two-dimensional echocardiography can be used to predict outcome.

Endothelin at Pathophysiological Concentrations Mediates Coronary Vasoconstriction via the Endothelin-A Receptor

BACKGROUND Endothelin-1 (ET-1) is an endothelium-derived vasoconstrictor peptide. Controversy persists regarding the predominant ET receptor that mediates coronary vasoconstriction at pathophysiological concentrations. The aim of the present study was to test the hypothesis that ET mediates local coronary vasoconstriction via the ET-A receptor at low concentrations of exogenous ET-1 designed to mimic pathophysiological states compared with pharmacological concentrations. METHODS AND RESULTS ET-1 (group 1, n = 5) or sarafotoxin, a specific ET-B receptor agonist (group 3, n = 6) (each at 2 ng/kg per minute), was infused into the left circumflex coronary artery in the anesthetized dog. In group 2 dogs (n = 5), the same dose of ET-1 was infused with 4 micrograms/kg per minute of the specific ET-A receptor antagonist FR-139317. In group 4 (n = 5), the same dose of sarafotoxin was infused with 50 micrograms/kg per minute of the specific inhibitor of nitric oxide formation, NG-monomethyl-L-arginine (L-NMMA). No difference in hemodynamics, coronary blood flow (CBF), coronary vascular resistance (CVR), or coronary artery diameter (CAD) was observed at baseline between the groups. In group 1, intracoronary ET-1 significantly decreased CBF and CAD in association with an increase in CVR. The percentage decrease in CBF and CAD in the group that received ET-1 and the ET-A receptor antagonist (group 2) was significantly less than that in the group that received ET-1 alone (group 1) (-12 +/- 3% versus -48 +/- 6% [P < .001] and -4.6 +/- 0.8 versus 1.0 +/- 0.3 [P < .05], respectively). The administration of the ET-A receptor antagonist (group 2) abolished the ET-mediated increase in CVR (7 +/- 5% versus 105 +/- 21%, P < .005). There was no significant effect on CBF, CVR, or CAD in the group receiving sarafotoxin alone (group 3). The administration of L-NMMA and sarafotoxin (group 3). The administration of L-NMMA and sarafotoxin (group 4) resulted in a significant percentage decrease in CBF compared with the group that received sarafotoxin alone (-28 +/- 7% versus -8 +/- 2% [P < .05]). CONCLUSIONS The present study demonstrates that low concentrations of exogenous ET-1, which may mimic pathophysiological concentrations, result in coronary vasoconstriction mediated predominantly via the ET-A receptor because such vasoconstriction is significantly attenuated by blockade with FR-139317. The ET-B receptor may have a dual vasoconstrictive and vasodilatory effect.

Coronary vascular remodeling in association with endothelial dysfunction

Vascular remodeling has been demonstrated in advanced and early coronary artery disease. Whereas the endothelium may play a role in the adaptive process of vascular remodeling, it is not known if this process occurs in association with changes in coronary blood flow reserve. Early coronary atherosclerosis is characterized by endothelial dysfunction which is manifested by an abnormal coronary blood flow in response to the endothelium-dependent vasodilator acetylcholine. This study was designed to test the hypothesis that coronary vascular remodeling occurs in association with coronary endothelial dysfunction early in the development of coronary atherosclerosis. Thirty-six patients found to have normal coronary angiograms or mild coronary artery disease were studied. Acetylcholine was infused into the left anterior descending artery. Patients were divided into 2 groups based on their coronary blood flow response to acetylcholine. Intravascular ultrasound measurements of the proximal left anterior descending diameter and area were obtained. Vessel diameter and area were measured at the external elastic membrane and indexed to body surface area. Vessel diameter and area were greater in patients with abnormal than normal responses to acetylcholine (5.2 +/- 0.3 mm and 19.5 +/- 0.9 mm2 vs 3.9 +/- 0.3 mm and 12.3 +/- 1.0 mm2; p <0.02, respectively). This difference persisted when measurements were indexed to body surface area. The current study suggests in vivo in humans that coronary vascular remodeling characterized by enlargement of the proximal coronary arteries occurs in association with endothelial dysfunction early in the course of coronary artery disease.

Evaluation of patients with minimally obstructive coronary artery disease and angina.

Atherosclerotic coronary artery disease is a progressive process adversely affecting the integrity of the coronary vasculature. In past years, most studies have focused on the morphological changes leading to compromised coronary blood flow in atherosclerosis. However, in recent years it has become apparent that abnormal coronary vasomotor regulation may precede or accompany gross morphological changes in coronary atherosclerotic disease. In fact, the pathophysiology of angina pectoris in many patients with risk factors for atherosclerosis and minimally obstructive disease may involve abnormal coronary vasomotor tone regulation. The aim of the present article is to describe a clinical approach to patients with angina pectoris and minimally obstructive coronary artery disease based on current knowledge of coronary vasomotor regulation.

Pacemaker Induced Mitral Regurgitation: An Alternative Form of Pacemaker Syndrome

A patient in atrial fibrillation was referred for mitral valve replacement due to severe mitral regurgitation. A cardiac pacemaker had previously been implanted. Cardiac catheterization demonstrated large V waves in the wedge pressure tracing during ventricular pacing, which were not present during native conduction. A left ventriculogram demonstrated severe mitral regurgitation during ventricular pacing, but not during native conduction. This patient, in atrial fibrillation, had severe mitral regurgitation induced by ventricular pacing and not by native conduction. Pacemaker syndrome may be caused by mitral regurgitation that is probably not secondary to AV dissociation, but rather the result of dyssyn‐chronous ventricular contraction.

Acute Endothelin-Receptor Inhibition Does Not Attenuate Acetylcholine-Induced Coronary Vasoconstriction in Experimental Hypercholesterolemia

Endothelin (ET) may mediate the enhanced coronary vasoconstriction associated with hypercholesterolemia. We hypothesized that short-term inhibition of ET receptors attenuates the coronary epicardial vasoconstrictor response to acetylcholine in experimental hypercholesterolemia. ET-1 (group I, n=5; 5 ng x kg[-1] x min[-1]) and acetylcholine (group III, n=7; 10[-6] to 10[-4] mol/L) were given by intracoronary infusion in pigs. ET-1 and acetylcholine were also infused with the specific ETA-receptor blocker FR-139317 (5 microg x kg[-1] x min[-1]; group II, n=6; group IV, n=6). Acetylcholine was also infused with the combined ET-receptor blocker, bosentan (0.5 mg/kg plus 1 mg x kg[-1] x h[-1], group V, n=5). The ETB-receptor agonist sarafotoxin 6c (5 ng x kg[-1] x min[-1]; n=4) was also infused. The percentage change in coronary artery diameter (%deltaCAD) to the infusions was measured at baseline and after 10 weeks of high-cholesterol diet in all animals. Sarafotoxin 6c mildly reduced %deltaCAD at baseline and 10 weeks (-10+/-2% and -12+/-3%, respectively). FR-139317 did not attenuate the epicardial vasoconstrictor response to ET-1 at baseline (%deltaCAD -18+/-8% for group I versus -12+/-6% for group II; P=NS) but did at 10 weeks (%deltaCAD -77+/-14% for group I versus -14+/-6% for group II; P<.05). FR-139317 did not affect the response to acetylcholine at baseline (%deltaCAD 5+/-2% for group III versus 7+/-3% for group IV, P=NS) or at 10 weeks (%deltaCAD -23+/-12% for group III versus -19+/-7% for group IV; P=NS). Bosentan did not affect the response to acetylcholine at baseline or 10 weeks. Short-term ET-receptor inhibition in experimental hypercholesterolemia attenuated the enhanced coronary epicardial vasoconstrictor effects of ET-1 but not acetylcholine-induced coronary epicardial vasoconstriction, suggesting that acetylcholine-induced coronary epicardial vasoconstriction may not be mediated by ET receptors.

New insight into coronary endothelial dysfunction: Role of endothelin

The coronary endothelium plays a central role in the modulation of coronary vascular tone via the production and release of vasoactive mediators. A number of cardiovascular disease states are associated with coronary endothelial dysfunction, which results in an imbalance between vasoactive substances. Endothelin is a potent vasoconstrictor produced by the coronary endothelium and has been implicated in the pathogenesis of coronary endothelial dysfunction. This review examines the relationship between endothelin and coronary endothelial dysfunction as it occurs in a number of cardiovascular disease states and explores potential therapeutic options.

Prognosis with Abnormal Thallium Images in the Absence of Significant Coronary Artery Disease

In the presence of coronary artery disease (CAD), thallium imaging has been reported to add prognostic information that is independent of coronary anatomy. To investigate the prognostic importance of thallium imaging in the absence of significant CAD, 87 patients (65 men, 22 women) with abnormal thallium images without significant CAD were followed for a median duration of 22 months (range 11 to 50). Tomographic thallium images obtained immediately and 4 hours after exercise were interpreted by 2 experienced observers who graded thallium uptake in 24 segments in 3 views (short axis, horizontal long axis, vertical long axis) on a 5-point scale (normal; mildly, moderately, or severely reduced; absent). All patients had an abnormal thallium study, defined as a reversible defect of at least mild severity or a fixed defect of at least moderate severity seen in > or = 2 views, or a combination of these, and a coronary angiogram with stenosis not > or = 70% in diameter narrowing. Eighty-two patients had at least 1 reversible segment, and 26 patients had defects in > or = 2 coronary artery distributions. During follow-up there were no deaths or myocardial infarctions. Coronary angioplasty and bypass surgery were performed in 2 patients. Three-year survival without myocardial infarction or revascularization was 97%. Patients with abnormal thallium images in the absence of significant CAD have an excellent short-term prognosis.

Altered coronary endothelial function in a patient with asymptomatic left ventricular dysfunction

Coronary endothelial dysfunction has been demonstrated in patients with symptomatic heart failure. Furthermore the endothelium has been implicated in the pathogensis of cardiomyopathy in patients with normal coronary angiograms and no other known causes of heart failure. Herein we describe an asymptomatic patient with an early cardiomyopathy and abnormal coronary endothelial function. There was no evidence for coronary disease by both angiography and intravascular ultrasound. Epicardial coronary artery vasoconstriction and a decrease in coronary blood flow was noted during the intracoronary infusion of graded concentrations of acetylcholine. This case demonstrates that endothelial dysfunction occurs in the setting of asymptomatic left ventricular dysfunction and highlights the potential importance of the endothelium in the early development of heart failure.