Pathogenesis of hypertrophic cardiomyopathy. Impact of growth factors on left ventricular anatomy.

AIM: The aim of this study was to evaluate the effect of insulin-like growth factor 1 (IGF1) and transforming growth factor beta-1 (TGFbeta-1) on collagen turnover, left ventricular (LV) hypertrophy and on passive diastolic function of the LV in hypertrophic cardiomyopathy (HCM). METHODS: This study group comprised 34 patients with non-dilated HCM. Procollagen I amino-terminal propeptide (PINP) and collagen I carboxy-terminal telopeptide (ICTP) were measured by radioimmunoassay. Matrix metalloproteinase 9 (MMP 9), IGF1 and TGFalfa-1 were determined by enzyme-linked immunosorbent assay. The difference in duration between transmitral forward (A) and pulmonary venous retrograde (Ar) waves, was considered as an estimate of passive diastolic function; the ratio between the peak flow velocity at rapid filling at the mitral level (E) and E' measured by tissue Doppler was considered an estimate of active diastolic function. LV mass was measured and normalized to body surface area (LVMi) by cardiac magnetic resonance imaging. RESULTS: LVMi correlates to E/E' (r=0.597, P=0.019 ) and is inversely related to A-Ar (r=0.453, P=0.015). TGFbeta-1 is directly related to active MMP 9 (r=0.439, P=0.012 ). IGF1 is directly related to PICP-ICTP (r=0.347, P=0.501), that expresses the balance between collagen I synthesis and its degradation. CONCLUSION: The study demonstrated that in HCM, LVMi influences active and passive diastolic dysfunction and that IGF1 stimulates collagen synthesis and TGFbeta-1 is related to LV hypertrophy.

Evaluation of the left ventricular anatomy in hypertrophic cardiomyopathy: comparison between echocardiography and cardiac magnetic resonance imaging.

AIM: The aim of this study was to assess the relationship between echocardiographic indexes of left ventricular (LV) hypertrophy with LV mass (LVM) obtained at cardiac magnetic resonance (CMR) in a population of patients with hypertrophic cardiomiopathy (HCM). METHODS: Thirty-nine patients with HCM underwent echocardiography and CMR. By echocardiography maximal wall thickness (MWT), Spirito' and Maron's hypertrophy index and the Wigle's score were obtained. Absolute LVM was measured through CMR and indexed to body surface area (LVMi). Data were analysed using linear regression analysis. RESULTS: In 31% of patients there was an incomplete echocardiographic LV anatomic characterization. However, there was a good correlation between MWT measured at echocardiography and at CMR (P<0.001; r=0.755). Overall echocardiographic indexes of LV hypertrophy correlate with either LVM and LVMi: MWT (P=0.008, r=0.420 and P=0.003, r=0.467, respectively); Spirito' and Maron's hypertrophy index (P=0.003, r=0.551 and P=0.001, r=0.606, respectively) and Wigle's score (P=0.004, r=0.522 and P=0.004, r=0.522, respectively). CONCLUSION: In our HCM population, although a complete anatomic LV anatomic characterization was not obtained by echocardiography in all patients, echocardiographic hypertrophic indexes showed a good correlation with LVM obtained by CMR.

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.

Aetiology and pathogenesis of hypertrophic cardiomyopathy.

UNLABELLED: The term hypertrophic cardiomyopathy is used to describe an autosomal dominant cardiac disorder, characterized by myocyte hypertrophy and disarray, interstitial fibrosis and small vessel disease, with or without macroscopic hypertrophy. More than 100 mutations in ten genes, all encoding sarcomeric proteins, have been identified as responsible for this disease. Mutations in the genes for beta-myosin heavy chain, myosin binding protein-C, and cardiac troponin T are the most common. Other genes involved are alpha-tropomyosin, cardiac troponin-I, essential and regulatory light chains, alpha-cardiac actin, titin, and alpha-myosin heavy chain. Some mutations are more frequently associated with a given phenotype, but no particular phenotype is mutation specific; in fact, some mutations exhibit highly variable clinical, electrocardiographic and echocardiographic manifestations. This variability in the phenotypic manifestations is probably due to the influence of environmental factors and/or modifier genes. While the aetiology of hypertrophic cardiomyopathy has been extensively elucidated, its pathogenesis is not completely understood. Mutated proteins are incorporated in the sarcomere and impair myocyte contractility. This probably triggers the compensatory local release of trophic factors, which influence the development of the typical anatomical features of the disease, with a pathway similar to that observed in secondary, pressure overload hypertrophy. CONCLUSIONS: The various pathological cardiac changes seen in hypertrophic cardiomyopathy are probably due to a compensatory response to impaired myocyte function resulting from mutations in the genes encoding sarcomeric proteins.

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.

Infective endocarditis in hypertrophic cardiomyopathy: prevalence, incidence, and indications for antibiotic prophylaxis.

BACKGROUND: The literature on infective endocarditis in hypertrophic cardiomyopathy (HCM) is virtually confined to case reports. Consequently, the risk of endocarditis in HCM remains undefined. METHODS AND RESULTS: We assessed the occurrence of endocarditis in 810 HCM patients evaluated between 1970 and 1997. Endocarditis was diagnosed in 10 patients, 2 of whom were excluded from analysis of prevalence and incidence because they were referred for acute endocarditis. At first evaluation, echocardiographic features consistent with prior endocarditis were identified in 3 of 808 patients, a prevalence of 3.7 per 1000 patients (95% CI, 0.8 to 11). Of 681 patients who were followed, 5 developed endocarditis, an incidence of 1.4 per 1000 person-years (95% CI, 0.5 to 3.2); outflow obstruction was present in each of these 5 patients and was associated with the risk of endocarditis (P=0.006). In the 224 obstructive patients, incidence of endocarditis was 3.8 per 1000 person-years (95% CI, 1.6 to 8.9) and probability of endocarditis 4. 3% at 10 years. Left atrial size was also associated with the risk of endocarditis (P=0.007). In patients with both obstruction and atrial dilatation (>/=50 mm), incidence of endocarditis increased to 9.2 per 1000 person-years (95% CI, 2.5 to 23.5). Analysis of all 10 patients with endocarditis identified outflow obstruction in each and atrial dilatation in 7. CONCLUSIONS: Endocarditis in HCM is virtually confined to patients with outflow obstruction and is more common in those with both obstruction and atrial dilatation. These results indicate that antibiotic prophylaxis is required only in patients with obstructive HCM.

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.

Identification of viable myocardium in patients with chronic coronary artery disease using rest-redistribution thallium-201 tomography: optimal image analysis.

UNLABELLED: With the widely used 50% threshold, sensitivity is high, but specificity is low in detecting viable myocardium on 201Tl SPECT. In this study, we sought to identify the best threshold for semiquantitative 201Tl analysis. METHODS: Rest-redistribution 201Tl SPECT was performed in 46 patients with chronic coronary artery disease before and after myocardial revascularization. Regional function was evaluated by two-dimensional echocardiography before and after myocardial revascularization using a 3-point scale (1 = normal, 2 = hypokinetic, 3 = a/dyskinetic). Myocardial segments with abnormal systolic function were defined as viable if the systolic function score decreased > or = 1 after myocardial revascularization. A second group of 12 patients with chronic coronary artery disease constituted the validation population. Sensitivity-specificity curves, as well as receiver operating characteristic curves, for rest and redistribution mages were generated by varying the 201Tl uptake threshold. RESULTS: A 65% threshold uptake using resting images was found to be the best for detecting a/dyskinetic segments that improve after myocardial revascularization from those that do not improve. Sensitivity was lower with a 65% threshold (75%) than with a 50% threshold (90%, p < 0.05), but specificity was higher (76% versus 26%, p < 0.05) resulting in better accuracy (76% versus 57%, p < 0.05) and positive predictive value (77% versus 55%), while the negative predictive value was not different (69% versus 75%, p not significant). The area under the receiver operating characteristic curve was significantly (p < 005) larger for rest (0.80 +/- 0.05) as opposed to redistribution (0.72 +/- 0.05) images. Similar results were obtained in a subgroup of patients with low ejection fraction. Significant correlations between the percentage of revascularized viable segments and both the change in ejection fraction and in postrevascularization ejection fraction were found. When these findings were applied in the validation group, a gain in specificity, accuracy and positive predictive value was obtained with the 65% threshold compared with the 50% threshold. CONCLUSION: This study demonstrated that analysis of resting images and use of the 65% 201Tl uptake threshold is preferable for separating viable from not viable dyssynergic myocardial segments in patients with chronic coronary artery disease.

[Effects left ventricle asynchrony on systolic and diastolic function in patients with non-ischemic heart failure]. / Effetti dell'asincronia del ventricolo sinistro sulla funzione sistolica e diastolica nei pazienti con scompenso cardiaco con origine non ischemica.

INTRODUCTION: The asynchrony of the left ventricle--i.e., its nonuniform contraction and relaxation--is an important factor for left ventricular function. Heart failure is often related to abnormal systolic function, sometimes associated with a diastolic dysfunction. We studied the relationship of left ventricular asynchrony to left ventricular function in patients with nonischemic heart failure. MATERIAL AND METHODS: Radionuclide angiography at rest was performed in 25 patients with nonischemic heart failure and in 26 age and sex matched normal subjects. In addition to ejection fraction and peak filling rate, two indices of left ventricular asynchrony were calculated: the coefficient of variation of regional time to end systole and the coefficient of variation of regional time to peak filling rate. These factors indicate how disperse are the regional values of time to end systole and of time to peak filling rate. In fact, the higher the value, the greater the asynchrony. RESULTS: A significant (r = .46, p < .05) inverse correlation was found between the ejection fraction and the coefficient of variation of regional time to end systole in both the normal subjects and the heart failure patients, while the ejection fraction correlated significantly (r = .46, p < .05) with the coefficient of variation of regional time to peak filling rate only in the patients. Moreover, the peak filling rate was inversely correlated (r = .57, p < .05) with the coefficient of variation of regional time to peak filling rate in the heart failure patients but not in the normal subjects. CONCLUSIONS: These results suggest that left ventricular systolic and diastolic asynchrony may contribute to impair left ventricular systolic and diastolic function in patients with nonischemic heart failure.

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.

Noninvasive evaluation of left ventricular diastolic function in hypertrophic cardiomyopathy.

Diastolic dysfunction is common in hypertrophic cardiomyopathy (HC). Previous studies suggest that Doppler transmitral flow velocity profiles, and the left atrial (LA) M-mode echogram can be used noninvasively to evaluate left ventricular (LV) diastolic function. However, this has not been proved in HC. In this study we determined the relation of Doppler transmitral flow velocity profiles and the LA M-mode echograms to invasive indexes of LV diastolic function in patients with HC. We studied 25 patients with HC, while off drugs, and calculated LA global and active fractional shortening and the slope of both early and late displacement of the posterior aortic wall during LA emptying by M-mode echocardiography. We calculated peak velocity of early (E) and atrial (A) filling, E to A ratio, and E-wave deceleration time by pulsed Doppler echocardiography, and simultaneous radionuclide angiography, LV pressures, time constant of isovolumic relaxation tau, and the constant of chamber stiffness k by cardiac catheterization. The time constant of isovolumic relaxation tau correlated with the slope of early posterior aortic wall displacement (r = 0.59; p <0.01). LV end-diastolic pressure correlated with global LA fractional shortening (r = -0.75; p <0.001); the constant of chamber stiffness k correlated with active LA fractional shortening (r = -0.53; p <0.02). In a subset of 13 patients, in whom echocardiography and cardiac catheterization were performed simultaneously, similar results were found. LA M-mode recordings provide a more reliable noninvasive assessment of diastolic function in HC than mitral Doppler indexes.

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.

Heart rate variability in patients with hypertrophic cardiomyopathy: association with clinical and echocardiographic features.

Autonomic dysfunction has been reported in patients with hypertrophic cardiomyopathy. To evaluate the influence of different clinical and echocardiographic features of the disease on sympathovagal balance, as assessed by heart rate variability, 33 patients with hypertrophic cardiomyopathy and 33 healthy volunteers underwent echocardiographic examination and 24-hour electrocardiogram Holter recording. Measures of vagal modulation of heart rate were lower in patients with hypertrophic cardiomyopathy than in controls, particularly in those exhibiting syncope, exertional chest pain, dyspnea, or moderate or severe mitral regurgitation. Furthermore, the age-corrected multiple regression analysis showed that the parasympathetic cardiac control was inversely related to left atrial dimension and directly related to left ventricular end-systolic dimension. Therefore in hypertrophic cardiomyopathy the parasympathetic withdrawal is more evident in patients with symptoms than in those without; the reduction in left ventricular end-systolic dimension and the increase in left atrial size are the echocardiographic features that most influence the sympathovagal balance.

[Left ventricular function in patients with chronic ischemic cardiopathy: relationship with the status of myocardial perfusion]. / La funzione ventricolare sinistra nei pazienti con cardiopatia ischemica cronica: relazione con lo stato perfusivo micardico.

The aim of this study was the evaluation of left ventricular function compared to myocardial perfusion in patients with chronic coronary artery disease (CAD). Thirty-two patients with chronic CAD (27 men and 5 women, mean age 58 +/- 9 years) underwent radionuclide angiography and rest-redistribution thallium-201 (TI-201) single photon emission Computed Tomography (SPECT). Ejection fraction (EF, %), peak filling rate (PFR, end diastolic volume/second), and the coefficient of variation of the regional time to PFR (CV-TPFR, %) were computed. Patients with severe irreversible defects (i.e. with TI-201 uptake < 50%) had lower EF (42 +/- 7% vs 52 +/- 11%, p < 0.01) and lower PFR (1.9 +/- 0.4 vs 3.1 +/- 1.0, p < 0.0005) than those without. Patients with severe irreversible perfusion defects in the left anterior descending artery territory had lower EF (41 +/- 6% vs 50 +/- 11%, p < 0.01), lower PFR (1.8 +/- 0.3 vs 2.8 +/- 1.0, p < 0.005), and higher CV-TPFR (39 +/- 22 vs 13 +/- 7, p < 0.001) than those without. The results of the present study indicate that in patients with chronic CAD left ventricular systolic and diastolic function is more deteriorated when the left anterior descending artery is involved. Similarly, the presence of severe irreversible perfusion defects is clearly associated with significantly lower EF and PFR.

Assessment of myocardial viability in patients with chronic coronary artery disease. Rest-4-hour-24-hour 201Tl tomography versus dobutamine echocardiography.

BACKGROUND: To date, late redistribution after resting 201Tl injection has not been evaluated. In addition, the concordance between resting 201Tl imaging and dobutamine echocardiography in identifying viable myocardium has not been assessed. METHODS AND RESULTS: Forty patients with coronary artery disease underwent rest-4-hour-24-hour 201Tl tomography and dobutamine echocardiography (5 to 10 micrograms.kg-1.min-1). Late redistribution occurred in 46 (21%) of 219 persistent defects at 4 hours. Systolic function and contractile reserve were similar among persistent defects at 4 hours with and without late redistribution. Contractile reserve was more frequent in segments with normal 201Tl uptake (59%), completely reversible defects (53%), or mild to moderate defects at 4 hours (56%) compared with severe defects (14%; P < .02 versus all). Of 105 hypokinetic segments, 99 (94%) were viable by 201Tl, and 88 (84%) showed contractile reserve. In contrast, of 155 akinetic segments, 119 (77%) were viable by 201Tl, but only 34 (22%) had contractile reserve. Concordance between 201Tl and dobutamine was 82% in hypokinetic segments but 43% in akinetic segments. In 109 revascularized segments, positive accuracy for functional recovery was 72% for 201Tl and 92% for dobutamine, whereas negative accuracy was 100% and 65%, respectively. Sensitivity was 100% for 201Tl and 79% for dobutamine. CONCLUSIONS: Late redistribution occurs in one fifth of persistent defects at 4 hours, and it does not correlate to systolic function or contractile reserve. Dobutamine and 201Tl yield concordant information in the majority of hypokinetic segments, whereas concordance is low in akinetic segments. Dobutamine demonstrates higher positive accuracy and sensitivity in predicting recovery of dysfunctional myocardium, whereas 201Tl shows higher negative predictive accuracy but reduced positive accuracy.