Sympathetic nervous function in patients with hypertrophic cardiomyopathy assessed by [123I]-MIBG: relationship with left ventricular perfusion and function.

AIM: The aim of the present study was to evaluate [123I] MIBG uptake and clearance in patients with hypertrophic cardiomyopathy (HCM) and to assess their relationships with left ventricular function (systolic and diastolic) and perfusion. METHODS: Eleven consecutive patients with HCM (8 men and 3 women; mean age 38+/-12 years, none in the dilated phase) underwent (in separate days, in random order) [123I]-MIBG scintigraphy, [(99m)Tc]-MIBI SPET at rest, and echocardiography. All patients were studied in fasting condition, and all medications were discontinued. [(99m)Tc]-MIBI SPET study was performed 1 hour after tracer injection. [123I]-MIBG study was acquired 5 minutes (planar) and 4 hours (planar and SPET) after the i.v. injection of [123I]-MIBG. Heart to mediastinum ratio (H/M) was computed at 4 hours. Wash out rate (WOR) was computed as: (H early - H delayed)/(H early), after decay correction. Both [123I]-MIBG and [(99m)Tc]-MIBI SPET were analyzed on 3 short axis views (apical, middle, and basal). Left ventricular outflow tract gradient (LVOTG), ejection fraction, volumes, septum thickness, and left atrial fractional shortening (LAFS) were evaluated on echocardiography. RESULTS: [123I]-MIBG WOR showed a positive relationship with LVOTG (r=0.84, p<0.001) and septum thickness (r=0.76, p<0.01), while a negative one was found with LAFS (r= -0.66, p<0.05). The study group was divided into: Group A (n=5) with higher, and Group B (n=6) with lower WOR than the median value (i.e. 11%). Group A patients had significantly lower LAFS (17.6+/-4.8 vs 26.8+/-7.2%, p<0.05), higher LVOTG (49+/-35 vs 3+/-3 mmHg), and thicker septum (21+/-2 vs 17+/-2 mm) than Group B patients. Inferior and septal wall [123I]-MIBG uptake on 4 hour SPET was significantly lower in Group A than in Group B. On the other hand, no differences were found in (99m)T-MIBI SPET rest regional uptake between the 2 subgroups of patients. CONCLUSION: These results suggest that cardiac sympathetic activity correlates to cardiac anatomy (i.e. degree of hypertrophy) and diastolic function in patients with HCM.

Determinants and clinical significance of natriuretic peptides and hypertrophic cardiomyopathy.

AIMS: Atrial and brain natriuretic peptide levels closely reflect impaired left ventricular function in patients with heart failure. In the present study we assessed the determinants and the clinical significance of atrial and brain natriuretic peptide plasma levels in hypertrophic cardiomyopathy. METHODS AND RESULTS: In 44 patients with hypertrophic cardiomyopathy (40+/-15 years) we evaluated: (a) atrial and brain natriuretic peptide plasma levels; (b) left ventricular hypertrophy; (c) left ventricular ejection fraction; (d) transmitral and pulmonary venous flow velocity patterns, and left atrial fractional shortening; (e) left ventricular outflow tract gradient; (f) maximal oxygen consumption. Left ventricular hypertrophy influenced only brain natriuretic peptide levels (r=0.32;P<0.05). Atrial and brain natriuretic peptide plasma levels did not correlate with left ventricular ejection fraction, but correlated with left ventricular outflow tract gradient (r=0.35;P<0.05; and r=0.40, P=0.022, respectively) and left atrial fractional shortening (r=-0.57;P<0.001, and r=-0.35;P<0.05, respectively). Atrial but not brain natriuretic peptide plasma levels were inversely related to maximal oxygen consumption (r=-0.35;P<0.05). By stepwise multiple regression analysis, left atrial fractional shortening and left ventricular outflow tract gradient were the only predictors of atrial and brain natriuretic peptide plasma levels, respectively. CONCLUSIONS: In hypertrophic cardiomyopathy, atrial natriuretic peptide plasma levels are mainly determined by diastolic function: this explains the relationship with exercise tolerance. In contrast, brain natriuretic peptide plasma levels are mainly determined by left ventricular outflow tract gradient.

Exercise capacity in hypertrophic cardiomyopathy depends on left ventricular diastolic function.

Some studies have demonstrated that left ventricular (LV) diastolic function is the principal determinant of impaired exercise capacity in hypertrophic cardiomyopathy (HC). In this study we sought the capability of echocardiographic indexes of diastolic function in predicting exercise capacity in patients with HC. We studied 52 patients with HC while they were not on drugs;12 of them had LV tract obstruction at rest. Diastolic function was assessed by M-mode and Doppler echocardiography by measuring: (1) left atrial fractional shortening, and the slope of posterior aortic wall displacement during early atrial emptying on M-mode left atrial tracing; and (2) Doppler-derived transmitral and pulmonary venous flow velocity indexes. Exercise capacity was assessed by maximum oxygen consumption by cardiopulmonary test during cycloergometer upright exercise. Maximum oxygen consumption correlated with the left atrial fractional shortening (r = 0.63, p <0.001), the slope of posterior aortic wall displacement during early atrial emptying (r = 0.55, p <0.001), age (r = -0.50; p <0.001), pulmonary venous diastolic anterograde velocity (r = 0.41, p <0.01), and the systolic filling fraction (r = -0.43; p <0.01). By stepwise multiple linear regression analysis, left atrial fractional shortening and the pulmonary venous systolic filling fraction were the only determinants of the maximum oxygen consumption (multiple r = 0.70; p <0.001). Exercise capacity did not correlate with Doppler-derived transmitral indexes. Thus, in patients with HC, exercise capacity was determined by passive LV diastolic function, as assessed by the left atrial M-mode and Doppler-derived pulmonary venous flow velocities.

Determinants of aortic artifacts during transesophageal echocardiography of the ascending aorta.

BACKGROUND: The origin of artifacts of the ascending aorta during transesophageal echocardiography has not been widely studied. This study was undertaken to investigate in vivo whether anatomic features could determine the appearance of artifacts. METHODS AND RESULTS: Transesophageal echocardiograms of 46 patients studied for suspected dissection with proven diagnosis (30 patients with and 16 without ascending aortic dissection) were reviewed. The incidence of artifacts was 46%, and it was similar in patients with and those without dissection (chi-square 0.516; P = not significant). Artifacts were located in the aortic lumen twice as far from the transducer as the atrial-aortic interface. The aortic diameter was larger in patients with than in those without artifacts (6.4 +/- 1.1 vs 4.2 +/- 0.9 cm, P <.001). An aortic diameter >5 cm and an atrial-aortic ratio 5.0 cm that exceeds the left atrial diameter with an atrial-aortic ratio

Influence of left ventricular cavity size on clinical presentation in hypertrophic cardiomyopathy.

The aim of this study was to assess whether left ventricular (LV) cavity size relates to functional impairment and syncope in patients with hypertrophic cardiomyopathy (HC). LV diastolic dysfunction influences functional limitation in HC. A reduced LV end-diastolic dimension may underlie impaired diastolic properties and be implicated in hemodynamic syncope. Eighty-two consecutive patients with HC (off drugs, in sinus rhythm) underwent echocardiography to measure LV end-diastolic dimension in the short-axis view (indexed to the body surface area) and radionuclide angiography (n = 50) to calculate peak filling rate (normalized to stroke counts/s). Patients in New York Heart Association functional classes II to IV had smaller LV end-diastolic dimension (23.2 +/- 2.6 vs 25.5 +/- 2.5 mm/M2, p = 0.0001) and lower peak filling rate (4.3 +/- 1.4 vs 5.1 +/- 1.3 stroke counts/s, p = 0.036) than those in New York Heart Association class I. LV end-diastolic diameter was correlated to peak filling rate (r = 0.37; p = 0.008). The most potent predictors of functional limitation were LV end-diastolic dimension (relative risk [RR] 0.63, confidence interval [CI] 0.45 to 0.88; p = 0.008), age (RR 1.09, CI 1.03 to 1.17; p = 0.003), and LV thickness score (RR 1.08, CI 1.02 to 1.13; p = 0.003). LV cavity size was smaller in patients with functional limitation irrespective of obstruction and hypertrophy. Patients with differed from those without a history of syncope for a smaller LV end-diastolic dimension (23.2 +/- 2.5 vs 25.0 +/- 2.7 mm/M2, p = 0.008), which was the only independent predictor of syncope (RR 0.77, CI 0.63 to 0.95; p = 0.013). Thus, a small LV cavity size is associated with functional limitation and history of syncope in HC.

Pattern of left ventricular filling in hypertrophic cardiomyopathy. Assessment by Doppler echocardiography and radionuclide angiography.

AIMS: The left ventricle in hypertrophic cardiomyopathy is anatomically and functionally non-uniform. This study was undertaken to verify whether a heterogeneity in the pattern of diastolic filling can be detected along the left ventricular inflow tract in hypertrophic cardiomyopathy. METHODS AND RESULTS: Early (E) and late (A) diastolic velocities were recorded by Doppler echocardiography at mitral and at mid-ventricular level in 16 normal volunteers and 30 patients with hypertrophic cardiomyopathy. Patients with hypertrophic cardiomyopathy also underwent radionuclide angiography to assess left ventricular function. E wave decreased significantly in normal volunteers (80 +/- 15 to 60 +/- 14 cm x s(-1); P<0.001), but it increased in hypertrophic cardiomyopathy (76 +/- 22 to 87 +/- 28 cm x s(-1) P=0.04), whereas the A wave decreased similarly in both. By multivariate analysis, systolic asynchrony and the ejection fraction of left ventricular lateral wall were directly related to the pattern of early filling progression (r=0.656, F=9.467; P<0.002). Moreover, systolic asynchrony showed a univariate direct correlation with changes in E velocity (r=0.42; P=0.02). CONCLUSION: Many patients with hypertrophic cardiomyopathy have an acceleration of filling within the left ventricular inflow tract; this phenomenon is directly related to systolic asynchrony and ejection fraction of the left ventricular lateral wall, suggesting increased suction.

Dual chamber pacing in hypertrophic cardiomyopathy: influence of atrioventricular delay on left ventricular outflow tract obstruction.

The impact of the duration of atrioventricular (AV) delay on obstruction in hypertrophic cardiomyopathy was evaluated in 12 patients by cardiac catheterization, and in 8 of them also by Doppler echocardiography. The AV delay was programmed in random order at 125, 100 and 75 ms in the invasive study and at 120, 100 and 80 ms after pacemaker implantation. The arterial pressure did not changed throughout the studies, whereas the gradient decreased significantly by reducing the AV delay value; the greater gradient reduction was obtained, in both studies, with the AV delay set between 75 or 80 and 100 ms. QRS duration increased significantly by reducing the AV delay during both studies. The widest QRS was not associated with the smallest gradient in all patients. Changes in gradients were similar during the invasive and noninvasive protocols.

Effects of diltiazem on left ventricular systolic and diastolic function in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HC) is characterized by impaired diastolic function, and left ventricular (LV) outflow tract obstruction in about one-fourth of patients. Verapamil improves diastolic properties, but may have dangerous adverse effects. This study investigates the effects of diltiazem on hemodynamics and LV function in 16 patients with HC who were studied with cardiac catheterization and simultaneous radionuclide angiography. Studies were performed during atrial pacing (15 beats above spontaneous rhythm) at baseline and during intravenous diltiazem administration (0.25 mg x kg(-1) over 2 minutes, and 0.014 mg x kg(-1) x min(-1). Diltiazem induced a systemic vasodilation (cardiac index: 3.4 +/- 1.0 to 4.0 +/- 1.0 L x min(-1) x m(-2), p = 0.003; aortic systolic pressure: 116 +/- 16 to 107 +/- 19 mm Hg, p = 0.007; systemic resistance index: 676 +/- 235 to 532 +/- 193 dynes x s x cm(-5) x m(-2), p = 0.006), not associated with changes in the LV outflow tract gradient. The end-systolic pressure/volume ratio decreased (30 +/- 42 to 21 +/- 29 mm Hg x ml(-1) x m(-2); p = 0.044). Pulmonary artery wedge pressure (11 +/- 5 to 15 +/- 6 mm Hg, p = 0.006), and peak filling rate increased (4.1 +/- 1.3 to 6.0 +/- 2.4 stroke counts x s(-1), p = 0.004). The time constant of isovolumetric relaxation tau decreased (74 +/- 40 to 59 +/- 38 ms, p = 0.045). The constant of LV chamber stiffness did not change. Thus, active diastolic function is improved by the acute administration of diltiazem by both direct action and changes in hemodynamics and loading conditions. LV outflow tract gradient does not increase despite systemic vasodilation. In some patients, however, a marked increase in obstruction and a potentially harmful elevation in pulmonary artery wedge pressure do occur. Passive diastolic function is not affected.