Clinical significance of transient left ventricular dilation assessed during myocardial Tc-99m sestamibi scintigraphy

OBJECTIVE: To assess the clinical significance of transient ischemic dilation of the left ventricle during myocardial perfusion scintigraphy with stress/rest sestamibi. METHODS: The study retrospectively analyzed 378 patients who underwent myocardial perfusion scintigraphy with stress/rest sestamibi, 340 of whom had a low probability of having ischemia and 38 had significant transient defects. Transient ischemic dilation was automatically calculated using Autoquant software. Sensitivity, specificity, and the positive and negative predictive values were established for each value of transient ischemic dilation. RESULTS: The values of transient ischemic dilation for the groups of low probability and significant transient defects were, respectively, 1.01 ± 0.13 and 1.18 ± 0.17. The values of transient ischemic dilation for the group with significant transient defects were significantly greater than those obtained for the group with a low probability (P<0.001). The greatest positive predictive values, around 50%, were obtained for the values of transient ischemic dilation above 1.25. CONCLUSION: The results suggest that transient ischemic dilation assessed using the stress/rest sestamibi protocol may be useful to separate patients with extensive myocardial ischemia from those without ischemia.

Value of the radiological study of the thorax for diagnosing left ventricular dysfunction in Chagas' disease

OBJECTIVE: To determine the value of the radiological study of the thorax for diagnosing left ventricular dilation and left ventricular systolic dysfunction in patients with Chagas' disease. METHODS: A cross-sectional study of 166 consecutive patients with Chagas' disease and no other associated diseases. The patients underwent cardiac assessment with chest radiography and Doppler echocardiography. Sensitivity, specificity, and positive and negative predictive values of chest radiography were calculated to detect left ventricular dysfunction and the accuracy of the cardiothoracic ratio in the diagnosis of left ventricular dysfunction with the area below the ROC curve. The cardiothoracic ratio was correlated with the left ventricular ejection fraction and the left ventricular diastolic diameter. RESULTS: The abnormal chest radiogram had a sensitivity of 50%, specificity of 80.5%, and positive and negative predictive values of 51.2% and 79.8%, respectively, in the diagnosis of left ventricular dysfunction. The cardiothoracic ratio showed a weak correlation with left ventricular ejection fraction (r=-0.23) and left ventricular diastolic diameter (r=0.30). The area calculated under the ROC curve was 0.734. CONCLUSION: The radiological study of the thorax is not an accurate indicator of left ventricular dysfunction; its use as a screening method to initially approach the patient with Chagas' disease should be reevaluated.

Right ventricular structure and function as possible determinants of surgical outcome 30 years after repair of tetralogy of Fallot

OBJECTIVE: To identify the variables that may be involved in the persistence of symptoms (functional class II, III, or IV vs. I) in patients being followed up for 30 years after surgical repair of tetralogy of Fallot. METHODS: Fifty-three patients (27 women), who underwent corrective surgery for tetralogy of Fallot between 1960 and 1970, were studied. Their ages ranged from 7 months to 26 years. At the end of follow-up, 13 patients were asymptomatic and the remaining were in functional class II (N=24), III (N=15), and IV (N=1). To differentiate asymptomatic from symptomatic patients, the following variables were analyzed: age at surgery, need for widening the pulmonary ring and trunk, need for a second (2nd OP) or 3rd operation, residual defect of the interventricular septum, residual regurgitation of the pulmonary valve, systolic gradient through the right ventricular outflow tract, right ventricular dilation or hypertrophy (RVH), cardiothoracic index (CTI), right and left ventricular ejection fraction (RVEF/LVEF), and arrhythmias. RESULTS: The univariate analysis showed an association between the presence of symptoms and the 2nd OP (P=0.03), an increase in the CTI (P=0.0001), moderate to severe RVH (P=0.002), and dilation (P=0.0003). In the logistic regression model, the combination of the 2nd OP (P=0.008), the RVH (P=0.002), and the reduction in RVEF (P=0.01) determined the presence of symptoms. CONCLUSION: Despite the surgical treatment, right ventricular remodeling and performance were the major determinants in the late follow-up of tetralogy of Fallot.

Myocardial dysfunction with increased ventricular compliance in volume overload hypertrophy

The aim this study was to evaluate systolic and diastolic function in volume overload induced myocardial hypertrophy in rats.Volume overload myocardial hypertrophy was induced in thirteen male Wistar rats by creating infrarenal arteriovenous fistula (AVF). The results were compared with a SHAM operated group (n = 11). Eight weeks after surgery, tail-cuff blood pressure was recorded, then rats were sacrificed for isolated heart studies using Langendorffs preparation.AVF rats presented increased left and right ventricular weights, compared to controls. The increased normalized ventricular volume (V0/LVW, 0.141 +/- 0.035 mL/g vs. 0.267 +/- 0.071 mL/g, P < 0.001) in the AVF group indicated chamber dilation. Myocardial hydroxyproline concentration remained unchanged. There was a significant decrease in +dP/dt (3318 +/- 352 mm Hg s(-1) vs. 2769 +/- 399 mm Hg s(-1); P=0,002), end-systolic pressure-volume relation (246 +/- 56 mm Hg mL(-1) vs. 114 +/- 63 mm Hg mL(-1);, P < 0,001), and -dP/dt (1746 +/- 240 min Hg s(-1) vs. 1361 +/- 217 mm Hg s(-1), P < 0.001) in the AVF group, which presented increased ventricular compliance (Delta V-25: SHAM=0.172 +/- 0.05 mL vs. AVF=0.321 +/- 0.072 mL, P < 0.001) with preserved myocardial passive stiffness (Strain(25): SHAM=13.5 +/- 3.0% vs. AVF=12.3 +/- 1.9%, P > 0.05).We conclude that volume-overload induced hypertrophy causes myocardial systolic and diastolic dysfunction with increased ventricular compliance. These haemodynamic features help to explain the long-term compensatory phase of chronic volume overload before transition to overt congestive heart failure. (c) 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.

A exposição crônica à fumaça do cigarro resulta em remodelação cardíaca e prejuízo da função ventricular em ratos

OBJETIVO: Determinar as alterações cardíacas estruturais e funcionais causadas pela exposição à fumaça do cigarro em ratos. MÉTODOS: Os animais foram aleatoriamente distribuídos em dois grupos: fumante (F), composto por 10 animais, expostos à fumaça do cigarro, na taxa de 40 cigarros/dia e controle (C), constituído por 10 animais não submetidos à exposição. Após 4 meses, os animais foram submetidos a estudo morfológico e funcional por meio do ecocardiograma. As variáveis estudadas foram analisadas pelo teste t ou pelo teste de Mann-Whitney. RESULTADOS: Os ratos fumantes apresentaram maior átrio esquerdo (F=4,2± 0,7mm; C=3,5±0,6mm; p<0,05), maiores diâmetros diastólicos (F=7,9±0,7mm; C=7,2±0,5mm; p<0,05) e sistólicos (F=4,1 ±0,5; C=3,4±0,5; p<0,05) do ventrículo esquerdo (VE). O índice de massa do VE foi maior nos animais fumantes (F=1,5 mg/kg± 0,2; C=1,3 mg/kg±0,2; p<0,05), e a fração de ejeção (F=0,85±0,03; C=0,89±0,03; p<0,05) e a fração de encurtamento (F=47,8 %±3,7; C=52,7%±4,6; p<0,05) maiores no grupo controle. Não foram identificadas diferenças nas variáveis de fluxo diastólico (onda E, na onda A e na relação E/A) transmitral. CONCLUSÃO: A exposição crônica à fumaça do cigarro resulta em remodelação cardíaca, com diminuição da capacidade funcional ventricular.

Prevalence and predictors of ventricular remodeling after anterior myocardial infarction in the era of modern medical therapy

Background: The consequences of aggressive therapy following a myocardial infarction (MI) on ventricular remodeling are not well established. Thus, the objective of this study was to analyze the prevalence, clinical characteristics, and predictors of left ventricular remodeling in the era of modern medical therapy.Material/Methods: Clinical characteristics and echocardiographic data were analyzed in 66 consecutive patients with anterior infarction at admission and at 6-month follow-up. Ventricular remodeling was defined as an increase of 10% in ventricular end-systolic or end-diastolic diameter.Results: In our study, 58% of patients presented with ventricular remodeling. Patients with remodeling possessed higher total plasma creatine kinase (CPK), MB-fraction (CPK-MB), heart rate, heart failure, shortness of breath, and reperfusion therapy than patients without remodeling. In contrast, patients with remodeling had a smaller ejection fraction, E-Wave deceleration time (EDT), and early (E' Wave) and late (A' Wave) diastolic mitral annulus velocity (average of septal and lateral walls), but a higher E/E' than patients without remodeling. Patients with remodeling used more diuretics, digoxin, oral anticoagulants and aldosterone antagonists than patients without remodeling. In the multivariate analyses, only E' Wave was an independent predictor of ventricular remodeling. Each 1 unit increase in the E' Wave was associated with a 59% increased odds of ventricular remodeling.Conclusions: In patients with anterior MI, despite contemporary treatment, ventricular remodeling is still a common event. In addition, diastolic function can have an important role as a predictor of remodeling in this scenario.

β-Carotene supplementation results in adverse ventricular remodeling after acute myocardial infarction

Objective: We studied the effects of β-carotene (BC) on ventricular remodeling after myocardial infarction. Methods: Myocardial infarction was induced in Wistar rats that were then treated with a BC diet (500 mg/kg of diet per day; MI-BC; n = 27) or a regular diet (MI; n = 27). Hearts were analyzed in vivo and in vitro after 6 mo. Results: BC caused decreased left ventricular wall thickness (MI = 1.49 ± 0.3 mm, MI-BC = 1.23 ± 0.2 mm, P = 0.027) and increased diastolic (MI = 0.83 ± 0.15 cm2, MI-BC = 0.98 ± 0.14 cm2, P = 0.020) and systolic (MI = 0.56 ± 0.12 cm2, MI-BC = 0.75 ± 0.13 cm2, P = 0.002) left ventricular chamber areas. With respect to systolic function, the BC group presented less change in fractional area than did controls (MI = 32.35 ± 6.67, MI-BC = 23.77 ± 6.06, P = 0.004). There was no difference in transmitral diastolic flow velocities between groups. In vitro results showed decreased maximal isovolumetric systolic pressure (MI = 125.5 ± 24.1 mmHg, MI-BC = 95.2 ± 28.4 mmHg, P = 0.019) and increased interstitial myocardial collagen concentration (MI = 3.3 ± 1.2%, MI-BC = 5.8 ± 1.7%, P = 0.004) in BC-treated animals. Infarct sizes were similar between groups (MI = 45.0 ± 6.6%, MI-BC = 48.0 ± 5.8%, P = 0.246). Conclusion: Taken together, these data suggest that BC has adverse effects on ventricular remodeling after myocardial infarction. © 2006 Elsevier Inc. All rights reserved.

Effects of Fluid Resuscitation on Cardiovascular Performance After Posttraumatic Pneumonectomy

Background: Several factors have been implicated in the high-mortality rate of posttraumatic pneumonectomy. In this study, we evaluated the hemodynamic and echocardiographic changes induced by pneumonectomy and fluid resuscitation after hemorrhagic shock. Methods: Fourteen dogs were bled to a target mean arterial pressure of 40 mmHg. The animals were assigned to two groups: control (no fluid resuscitation) and lactated Ringer`s (3 x shed blood volume). The left pulmonary hilum was cross clamped, and the animals were observed for 60 minutes. Systemic hemodynamics was evaluated using Swan-Ganz, arterial catheter, and ultrasonic flow probe. Systemic O(2)-derived variables were calculated. Ejection fraction was determined by two-dimensional echocardiography. Results: Fluid resuscitation improved the mean arterial pressure and systemic oxygen delivery. After pneumonectomy, no significant increase in right ventricular pressure was observed in the LR group. No signs of major ventricular dilation or changes in arterial oxygenation were observed. Conclusion: Our data suggest that pneumonectomy is not associated with early pulmonary hypertension; gentle fluid resuscitation improves cardiovascular performance and is not associated with an increase in right ventricular pressure.

Sarcomeric M-band alterations as a marker for human dilated cardiomyopathy

Purpose: The M-band is an important cytoskeletal structure in the centre of the sarcomere, believed to cross-link the thick filament lattice. Its main components are three closely related modular proteins from the myomesin gene family: Myomesin, M-protein and myomesin-3. Each muscle is characterized by its unique M-band protein composition, depending on the contractile parameters of a particular fiber. To investigate the role of the M-band in one of the most relevant and clinically increasing cardiac diseases, we analyzed the expression of myomesin proteins in dilated cardiomyopathy (DCM).Methods: In a previous study we analyzed mouse models suffering from DCM, demonstrating that the embryonic heart specific EH-myomesin splicing isoform was up-regulated directly corresponding to the degree of cardiac dysfunction and ventricular dilation. Based on this study, human ventricular and atrial samples (n=32) were obtained during heart surgery after informed consent and approval by an institutional review board. Patients were aged 30-70 years and suffered from dilated cardiomyopathy (DCM;n=13), Hypertrophic Cardiomyopathy (HCM;n=10) or served as controls (n=9). Patients suffering from DCM or HCM were in endstage heart-failure (NYHA III-IV) and either underwent heart transplantation or Left Ventricular Assist Device (LVAD) implantation. Heart samples from patients who underwent valve surgery or congenital heart surgery served as controls. Heart Samples were analyzed using RT-PCR, Western blot, and immunofluorescence.Results: By investigating the expression pattern of myomesins, we found that DCM is accompanied by specific M-band alterations, which were more pronounced in ventricular samples compared to the atrium. Changes in the amounts of different myomesins during DCM occurred in a cell-specific manner, leading to a higher heterogeneity of the cytoskeleton in cardiomyocytes through the myocardial wall with some cells switching completely to an embryonic phenotype.Conclusions: Here we present that the embryonic heart specific EH-myomesin isoform is up-regulated in human DCM. The alterations of the M-band protein composition might be part of a general adaptation of the sarcomeric cytoskeleton to unfavorable working conditions in the failing heart and may modify the mechanical properties of the cardiomyocytes. We suggest that the upregulation of EH-myomesin might play a pivotal role in DCM and might support classical imagingas a novel sarcomeric marker for this disease.

Myeloid differentiation factor-88/interleukin-1 signaling controls cardiac fibrosis and heart failure progression in inflammatory dilated cardiomyopathy.

RATIONALE: The myeloid differentiation factor (MyD)88/interleukin (IL)-1 axis activates self-antigen-presenting cells and promotes autoreactive CD4(+) T-cell expansion in experimental autoimmune myocarditis, a mouse model of inflammatory heart disease. OBJECTIVE: The aim of this study was to determine the role of MyD88 and IL-1 in the progression of acute myocarditis to an end-stage heart failure. METHODS AND RESULTS: Using alpha-myosin heavy chain peptide (MyHC-alpha)-loaded, activated dendritic cells, we induced myocarditis in wild-type and MyD88(-/-) mice with similar distributions of heart-infiltrating cell subsets and comparable CD4(+) T-cell responses. Injection of complete Freund's adjuvant (CFA) or MyHC-alpha/CFA into diseased mice promoted cardiac fibrosis, induced ventricular dilation, and impaired heart function in wild-type but not in MyD88(-/-) mice. Experiments with chimeric mice confirmed the bone marrow origin of the fibroblasts replacing inflammatory infiltrates and showed that MyD88 and IL-1 receptor type I signaling on bone marrow-derived cells was critical for development of cardiac fibrosis during progression to heart failure. CONCLUSIONS: Our findings indicate a critical role of MyD88/IL-1 signaling in the bone marrow compartment in postinflammatory cardiac fibrosis and heart failure and point to novel therapeutic strategies against inflammatory cardiomyopathy.

A-Kinase Anchoring Protein Lbc Coordinates a p38 Activating Signaling Complex Controlling Compensatory Cardiac Hypertrophy.

In response to stress, the heart undergoes a remodeling process associated with cardiac hypertrophy that eventually leads to heart failure. A-kinase anchoring proteins (AKAPs) have been shown to coordinate numerous prohypertrophic signaling pathways in cultured cardiomyocytes. However, it remains to be established whether AKAP-based signaling complexes control cardiac hypertrophy and remodeling in vivo. In the current study, we show that AKAP-Lbc assembles a signaling complex composed of the kinases PKN, MLTK, MKK3, and p38α that mediates the activation of p38 in cardiomyocytes in response to stress signals. To address the role of this complex in cardiac remodeling, we generated transgenic mice displaying cardiomyocyte-specific overexpression of a molecular inhibitor of the interaction between AKAP-Lbc and the p38-activating module. Our results indicate that disruption of the AKAP-Lbc/p38 signaling complex inhibits compensatory cardiomyocyte hypertrophy in response to aortic banding-induced pressure overload and promotes early cardiac dysfunction associated with increased myocardial apoptosis, stress gene activation, and ventricular dilation. Attenuation of hypertrophy results from a reduced protein synthesis capacity, as indicated by decreased phosphorylation of 4E-binding protein 1 and ribosomal protein S6. These results indicate that AKAP-Lbc enhances p38-mediated hypertrophic signaling in the heart in response to abrupt increases in the afterload.

Myocardial contractility of the isovolumetrically beating isolated rat heart

Several indexes of myocardial contractility have been proposed to assess ventricular function in the isovolumetrically beating isolated heart. However, the conclusions reached on the basis of these indexes may be influenced by ventricular geometry rather than contractility itself. The objective of the present study was to assess the performance of widely used contractility indexes in the isovolumetrically beating isolated heart in two experimental models of hypertrophy, the spontaneously hypertensive rat (SHR) and infrarenal aortocava fistula. Compared to normotensive controls (N = 8), SHRs with concentric hypertrophy (N = 10) presented increased maximum rate of ventricular pressure rise (3875 ± 526 vs 2555 ± 359 mmHg/s, P < 0.05) and peak of isovolumetric pressure (187 ± 11 vs 152 ± 11 mmHg, P < 0.05), and decreased developed stress (123 ± 20 vs 152 ± 26 g/cm², P < 0.05) and slope of stress-strain relationship (4.9 ± 0.42 vs 6.6 ± 0.77 g/cm²/%). Compared with controls (N = 11), rats with volume overload-induced eccentric hypertrophy (N = 16) presented increased developed stress (157 ± 38 vs 124 ± 22 g/cm², P < 0.05) and slope of stress-strain relationship (9 ± 2 vs 7 ± 1 g/cm²/%, P < 0.05), and decreased maximum rate of ventricular pressure rise(2746 ± 382 vs 3319 ± 352 mmHg, P < 0.05) and peak of isovolumetric pressure (115 ± 14 vs 165 ± 13 mmHg/s, P < 0.05). The results suggested that indexes of myocardial contractility used in experimental studies may present opposite results in the same heart and may be influenced by ventricular geometry. We concluded that several indexes should be taken into account for proper evaluation of contractile state, in the isovolumetrically beating isolated heart.

Collagen content, but not the ratios of collagen type III/I mRNAs, differs among hypertensive, alcoholic, and idiopathic dilated cardiomyopathy

Cardiac interstitial fibrosis may contribute to ventricular dysfunction and the prognosis of patients with dilated cardiomyopathy. The objective of the present study was to determine if total myocardial collagen content and collagen type III/I (III/I ratio) mRNAs differ in hypertensive, alcoholic, and idiopathic dilated cardiomyopathy subjects. Echocardiography and exercise cardiopulmonary testing were performed in patients with idiopathic (N = 22), hypertensive (N = 12), and alcoholic (N = 11) dilated cardiomyopathy. Morphometric analysis of collagen was performed in fragments obtained by endomyocardial biopsy with picrosirius red staining. The collagen III/I ratio was determined by reverse transcription polymerase chain reaction. Samples of controls (N = 10) were obtained from autopsy. Echocardiographic variables and maximal oxygen uptake were not different among dilated cardiomyopathy groups. Collagen was higher in all dilated cardiomyopathy groups (idiopathic, hypertensive and alcoholic, 7.36 ± 1.09%) versus controls (1.12 ± 0.18%), P < 0.05. Collagen was lower in idiopathic dilated cardiomyopathy (4.97 ± 0.83%) than hypertensive (8.50 ± 1.11%) and alcoholic (10.77 ± 2.09%) samples (P < 0.005 for both). The collagen III/I ratio in all samples from dilated cardiomyopathy patients was higher compared to that in controls (0.29 ± 0.04, P < 0.05) but was the same in the samples from idiopathic (0.77 ± 0.07), hypertensive (0.75 ± 0.07), and alcoholic (0.81 ± 0.16) dilated cardiomyopathy groups. Because of the different physical properties of the types of collagen, the higher III/I ratio may contribute to progressive ventricular dilation and dysfunction in dilated cardiomyopathy patients.

Beta-carotene supplementation attenuates cardiac remodeling induced by one-month tobacco-smoke exposure in rats

Objective: the objectives were to analyze the cardiac effects of exposure to tobacco smoke (ETS), for a period of 30 days, alone and in combination with beta-carotene supplementation (BC). Research methods and procedures: Rats were allocated into: Air (control, n = 13); Air + BC (n = 11); ETS (n = 11); and BC + ETS (n = 9). In Air + BC and BC + ETS, 500 mg of BC were added to the diet. After three months of randomization, cardiac structure and function were assessed by echocardiogram. After that, animals were euthanized and morphological data were analyzed post-morten. One-way and two-way ANOVA were used to assess the effects of ETS, BC and the interaction between ETS and BC on the variables. Results: ETS presented smaller cardiac output (0.087 +/- 0.001 vs. 0.105 +/- 0.004 l/min; p = 0.007), higher left ventricular diastolic diameter (19.6 +/- 0.5 vs. 18.0 +/- 0.5 mm/kg; p = 0.024), higher left ventricular (2.02 +/- 0.05 vs. 1.70 +/- 0.03 g/kg; p < 0.001) and atrium (0.24 +/- 0.01 vs. 0.19 +/- 0.01 g/kg; p = 0.003) weight, adjusted to body weight of animals, and higher values of hepatic lipid hydroperoxide (5.32 +/- 0.1 vs. 4.84 +/- 0.1 nmol/g tissue; p = 0.031) than Air. However, considering those variables, there were no differences between Air and BC + ETS (0.099 +/- 0.004 l/min; 19.0 +/- 0.5 mm/kg; 1.83 +/- 0.04 g/kg; 0.19 +/- 0.01 g/kg; 4.88 +/- 0.1 nmol/g tissue, respectively; p > 0.05). Ultrastructural alterations were found in ETS: disorganization or loss of myofilaments, plasmatic membrane infolding, sarcoplasm reticulum dilatation, polymorphic mitochondria with swelling and decreased cristae. In BC + ETS, most fibers showed normal morphological aspects. Conclusion: One-month tobacco-smoke exposure induces functional and morphological cardiac alterations and BC supplementation attenuates this ventricular remodeling process.

Myocardial contractility of the isovolumetrically beating isolated rat heart

Several indexes of myocardial contractility have been proposed to assess ventricular function in the isovolumetrically beating isolated heart. However, the conclusions reached on the basis of these indexes may be influenced by ventricular geometry rather than contractility itself. The objective of the present study was to assess the performance of widely used contractility indexes in the isovolumetrically beating isolated heart in two experimental models of hypertrophy, the spontaneously hypertensive rat (SHR) and infrarenal aortocava fistula. Compared to normotensive controls (N = 8), SHRs with concentric hypertrophy (N = 10) presented increased maximum rate of ventricular pressure rise (3875 ± 526 vs 2555 ± 359 mmHg/s, P < 0.05) and peak of isovolumetric pressure (187 ± 11 vs 152 ± 11 mmHg, P < 0.05), and decreased developed stress (123 ± 20 vs 152 ± 26 g/cm², P < 0.05) and slope of stress-strain relationship (4.9 ± 0.42 vs 6.6 ± 0.77 g/cm²/%). Compared with controls (N = 11), rats with volume overload-induced eccentric hypertrophy (N = 16) presented increased developed stress (157 ± 38 vs 124 ± 22 g/cm², P < 0.05) and slope of stress-strain relationship (9 ± 2 vs 7 ± 1 g/cm²/%, P < 0.05), and decreased maximum rate of ventricular pressure rise(2746 ± 382 vs 3319 ± 352 mmHg, P < 0.05) and peak of isovolumetric pressure (115 ± 14 vs 165 ± 13 mmHg/s, P < 0.05). The results suggested that indexes of myocardial contractility used in experimental studies may present opposite results in the same heart and may be influenced by ventricular geometry. We concluded that several indexes should be taken into account for proper evaluation of contractile state, in the isovolumetrically beating isolated heart.