Experimental Model of Gene Transfection in Healthy Canine Myocardium: Perspectives of Gene Therapy for Ischemic Heart Disease

OBJECTIVE: To assess the transfection of the gene that encodes green fluorescent protein (GFP) through direct intramyocardial injection. METHODS: The pREGFP plasmid vector was used. The EGFP gene was inserted downstream from the constitutive promoter of the Rous sarcoma virus. Five male dogs were used (mean weight 13.5 kg), in which 0.5 mL of saline solution (n=1) or 0.5 mL of plasmid solution containing 0.5 µg of pREGFP/dog (n=4) were injected into the myocardium of the left ventricular lateral wall. The dogs were euthanized 1 week later, and cardiac biopsies were obtained. RESULTS: Fluorescence microscopy showed differences between the cells transfected and not transfected with pREGFP plasmid. Mild fluorescence was observed in the cardiac fibers that received saline solution; however, the myocardial cells transfected with pREGFP had overt EGFP expression. CONCLUSION: Transfection with the EGFP gene in healthy canine myocardium was effective. The reproduction of this efficacy using vascular endothelial growth factor (VEGF) instead of EGFP aims at developing gene therapy for ischemic heart disease.

Benefits of exercise training in the treatment of heart failure: study with a control group

OBJECTIVE: Exercise training programs have been proposed as adjuncts to treatment of heart failure. The effects of a 3-month-exercise-training-program with 3 exercise sessions per week were assessed in patients with stable systolic chronic heart failure. METHODS: We studied 24 patients with final left ventricle diastolic diameter of 70±10mm and left ventricular ejection fraction of 37±4%. Mean age was 52±16 years. Twelve patients were assigned to an exercise training group (G1), and 12 patients were assigned to a control group (G2). Patients underwent treadmill testing, before and after exercise training, to assess distance walked, heart rate, systolic blood pressure, and double product. RESULTS: In G2 group, before and after 3 months, we observed, respectively distance walked, 623±553 and 561± 460m (ns); peak heart rate, 142±23 and 146± 33b/min (ns); systolic blood pressure, 154±36 and 164±26 mmHg (ns); and double product, 22211± 6454 and 24293±7373 (ns). In G1 group, before and after exercise, we observed: distance walked, 615±394 and 970± 537m (p<0.003) peak heart rate, 143±24 and 143±29b/min (ns); systolic blood pressure, 136±33 and 133±24 mmHg (ns); and double product, 19907± 7323 and 19115±5776, respectively. Comparing the groups, a significant difference existed regarding the variation in the double product, and in distance walked. CONCLUSION: Exercise training programs in patients with heart failure can bring about an improvement in physical capacity.

Pregnancy and peripartum cardiomyopathy: a comparative and prospective study

OBJECTIVE: To assess pregnancy outcome in women with peripartum cardiomyopathy and to compare it with idiopathic cardiomyopathy. METHODS: Twenty-six pregnant women, aged 28.4±6.1 years, with dilated cardiomyopathy were followed. Eighteen patients had peripartum cardiomyopathy [11 with persistent left ventricular systolic dysfunction (EF=45.2±2) and 7 with recovered ventricular function (EF=62.3±3.6)]. The 8 remaining patients had idiopathic cardiomyopathy (EF= 43.5±4.1). During the prenatal period, limited physical activity and a low-sodium diet were recommended, and hospitalization was recommended when complications occurred. RESULTS: Of the 26 patients, 11 (42.3%) had a normal delivery; 9(35.5%) had cardiac complications, 6 (22.2%) had obstetric complications. Two patients (7.7%) died. Two preterm pregnancies occurred, with 26 health newborns (2 sets of twins). Two miscarriages took place. The cardiac complication rate during pregnancy was lower (p<0.009) in the peripartum cardiomyopathy group without ventricular dysfunction and greater (p=0.01) in the idiopathic group when compared with the peripartum group with ventricular dysfunction. Changes in left ventricular ejection fraction were not observed (p<0.05) in the postpartum period, when compared with that during pregnancy in the 3 groups. CONCLUSION: Pregnancy in patients with dilated cardiomyopathy is associated with maternal morbidity. Left ventricular function is a prognostic factor and must be the most parameter when counseling patients with peripartum cardiomyopathy about a new pregnancy.

Comparison between young males and females with acute myocardial infarction

OBJECTIVE: To assess the differences between young males and females after acute myocardial infarction. METHODS: We retrospectively studied 236 patients (54 females and 182 males) after acute myocardial infarction and during hospital stay assessed the following parameters: risk factors; the treatment used; the pattern of coronary artery obstruction; left ventricular ejection fraction; complications; and, using a logistic regression model, the factors related to the occurrence of reinfarction and death. RESULTS: No significant difference was observed between the sexes in risk factors, pattern of coronary artery obstruction, and left ventricular function. The time interval between symptom onset and treatment was longer in females (p=0.03), who underwent thrombolysis (p=0.01) and angioplasty (p=0.03) less frequently than males did, but not myocardial revascularization. Female sex (OR = 5.98) and diabetes (OR = 14.52) were independent factors related to the occurrence of reinfarction and death. CONCLUSION: Young males and females after acute myocardial infarction did not differ in coronary risk factors, and clinical and hemodynamic characteristics. Females had their treatment started later, and they underwent chemical thrombolysis and angioplasty less frequently than males did. Female sex and diabetes were related to the occurrence of reinfarction and death.

Prognostic value of technetium-99m-labeled single-photon emission computerized tomography in the follow-up of patients after their first myocardial revascularization surgery

OBJECTIVE: To assess the prognostic value of Technetium-99m-labeled single-photon emission computerized tomography (SPECT) in the follow-up of patients who had undergone their first myocardial revascularization. METHODS: We carried out a retrospective study of 280 revascularized patients undergoing myocardial scintigraphy under stress (exercise or pharmacological stress with dipyridamole) and at rest according to a 2-day protocol. A set of clinical, stress electrocardiographic and scintigraphic variables was assessed. Cardiac events were classified as "major" (death, infarction, unstable angina) and "any" (major event or coronary angioplasty or new myocardial revascularization surgery). RESULTS: Thirty-six major events occurred as follows: 3 deaths, 11 infarctions, and 22 unstable anginas. In regard to any event, 22 angioplasties and 7 new surgeries occurred in addition to major events, resulting a total of 65 events. The sensitivity of scintigraphy in prognosticating a major event or any event was, respectively, 55% and 58%, showing a negative predictive value of 90% and 83%, respectively. Diabetes mellitus, inconclusive stress electrocardiography, and a scintigraphic visualization of left ventricular enlargement were significant variables for the occurrence of a major event. On multivariate analysis, abnormal myocardial scintigraphy was a predictor of any event. CONCLUSION: Myocardial perfusion tomography with Technetium-99m may be used to identify high-risk patients after their first myocardial revascularization surgery.

Doppler tissue imaging to assess systolic function in Chagas' disease

OBJECTIVE: To assess the usefulness of Doppler tissue imaging (DTI) for evaluating the systolic function of chagasic patients with and without electrocardiographic abnormalities, in comparision with echocardiographic study. METHODS: We studied 77 patients divided into 3 groups as follows: group 1 - control; group 2 - chagasic patients with normal electrocardiographic findings; and group 3 - chagasic patients with abnormal electrocardiographic findings. The following parameters were assessed: left ventricular dimensions and ejection fraction, left atrial dimensions and diastolic function on echocardiography. Systolic velocity and regional isovolumic contraction time (IVCTr) of the septal, anterior, lateral, posterior and inferior left ventricular walls were assessed on DTI. RESULTS: Left ventricular cavitary dimensions, ejection fraction and DTI systolic wave showed significant differences between groups 1 and 3 and between groups 2 and 3, which were not found between groups 1 and 2. IVCTr allowed a statistically significant discrimination among the 3 groups. CONCLUSION: DTI allowed discrimination among the different groups assessed, being superior to echocardiography in identifying early abnormalities of contractility, and, therefore, potentially useful for detecting incipient myocardial alterations in chagasic patients with normal electrocardiographic findings.

White-coat hypertension and normotension in the League of Hypertension of the Hospital das Clínicas, FMUSP: prevalence, clinical and demographic characteristics

OBJECTIVE: To assess the prevalence of white-coat normortension, white-coat hypertension, and white-coat effect. METHODS: We assessed 670 medical records of patients from the League of Hypertension of the Hospital das Clínicas of the Medical School of the University of São Paulo. White-coat hypertension (blood pressure at the medical office: mean of 3 measurements with the oscillometric device ³140 or ³90 mmHg, or both, and ambulatory blood pressure monitoring mean during wakefulness < 135/85) and white-coat normotension (office blood pressure < 140/90 and blood pressure during wakefulness on ambulatory blood pressure monitoring ³ 135/85) were analyzed in 183 patients taking no medication. The white-coat effect (difference between office and ambulatory blood pressure > 20 mmHg for systolic and 10 mmHg for diastolic) was analyzed in 487 patients on treatment, 374 of whom underwent multivariate analysis to identify the variables that better explain the white-coat effect. RESULTS: Prevalence of white-coat normotension was 12%, prevalence of white-coat hypertension was 20%, and prevalence of the white-coat effect was 27%. A significant correlation (p<0.05) was observed between white-coat hypertension and familial history of hypertension, and between the white-coat effect and sex, severity of the office diastolic blood pressure, and thickness of left ventricular posterior wall. CONCLUSION: White-coat hypertension, white-coat normotension, and white-coat effect should be considered in the diagnosis of hypertension.

Infective endocarditis: surgical therapy

OBJECTIVE: To assess the major causes of surgical morbidity and mortality in patients with infective endocarditis operated upon in a regional cardiology center. METHODS: Thirty-four patients underwent surgical treatment for infective endocarditis. Their ages ranged from 20 to 68 years (mean of 40.6) and 79% were males. Their NYHA functional classes were as follows: IV - 19 (55.8%) patients; III - 12 (35.2%) patients; II - 3 (8.8%) patients. Blood cultures were positive in only 32% of the cases. Eight patients had already undergone previous cardiac surgery, whose major indication (82.3%) was heart failure refractory to clinical treatment. RESULTS: Four (11.7%) patients died at the hospital. Follow-up was complete in 26 (86%) patients. Five (14.7%) patients died later, 12, 36, 48, 60, and 89 months after hospital discharge. Of the 21 patients being currently followed up, 1 is in NYHA functional class III, and 5 in NYHA functional class II. CONCLUSION: A high degree of clinical suspicion, at an early diagnosis, and indication of surgical treatment prior to deterioration of left ventricular function and installation of generalized sepsis may improve prognosis.

Endomyocardial fibrosis in infancy

The patient was a 4-month-old infant, who underwent persistent ductus arteriosus interruption with titanium clips at the age of 13 days and, since the age of 2 months, had crises of hypoxia and hypertonicity. After clinical investigation, the presence of pulmonary hypertension was confirmed and left ventricular inflow tract obstruction was suspected. The patient underwent surgical treatment at the age of 4 months, during which right and left ventricular endocardial fibrosis was identified. The fibrosis was resected, but the infant had an unfavorable clinical evolution with significant diastolic restriction and died on the sixth postoperative day. Anatomicopathological and surgical findings suggested endomyocardial fibrosis, although that pathology is very rare at the patient's age.

Regional myocardial function in healthy adults: assessment through tissue Doppler echocardiography

OBJECTIVE: To characterize left ventricular regional myocardial function through tissue Doppler echocardiography in healthy adults and to assess the influence of aging in this function. METHODS: In 45 healthy volunteers divided in two groups (< 45 and > 45 years old) we assessed longitudinal and radial regional function (velocities, times intervals and velocity-time integrals). Data were compared in each group and between groups. RESULTS: Systolic function: a) longitudinal: higher velocities and integrals in lateral and inferior walls and in basal segments, with a trend to reduction of these parameters with aging; b) radial: higher basal velocities, no significant change with aging. Diastolic function: a) longitudinal: higher velocities in lateral and inferior walls and in basal segments. With aging e and e/a velocities and integrals decreased, a increased and older individuals showed lower percentage of segments with e/a >1; b) radial: aging was associated with lower e and higher a velocities. CONCLUSION: 1) Tissue Doppler echocardiography detects physiological differences between regional myocardial function of different ventricular segments, in velocities, times intervals and integrals, with physiological heterogeneity and asynchrony; 2) Many of these data are age dependent; 3) Our data contribute to define normal values, and may become useful when compared with data from populations with heart diseases.

Subendocardial fibrosis in remote myocardium results from reduction of coronary driving pressure during acute infarction in rats

OBJECTIVE: To investigate the role of hemodynamic changes occurring during acute MI in subsequent fibrosis deposition within non-MI. METHODS: By using the rat model of MI, 3 groups of 7 rats each [sham, SMI (MI <30%), and LMI (MI >30%)] were compared. Systemic and left ventricular (LV) hemodynamics were recorded 10 minutes before and after coronary artery ligature. Collagen volume fraction (CVF) was calculated in picrosirius red-stained heart tissue sections 4 weeks later. RESULTS: Before surgery, all hemodynamic variables were comparable among groups. After surgery, LV end-diastolic pressure increased and coronary driving pressure decreased significantly in the LMI compared with the sham group. LV dP/dt max and dP/dt min of both the SMI and LMI groups were statistically different from those of the sham group. CVF within non-MI interventricular septum and right ventricle did not differ between each MI group and the sham group. Otherwise, subendocardial (SE) CVF was statistically greater in the LMI group. SE CVF correlated negatively with post-MI systemic blood pressure and coronary driving pressure, and positively with post-MI LV dP/dt min. Stepwise regression analysis identified post-MI coronary driving pressure as an independent predictor of SE CVF. CONCLUSION: LV remodeling in rats with MI is characterized by predominant SE collagen deposition in non-MI and results from a reduction in myocardial perfusion pressure occurring early on in the setting of MI.

Short- and midterm follow-up results of valvuloplasty with balloon catheter for congenital aortic stenosis

OBJECTIVE: To report short and midtem follow-up results of balloon aortic valvuloplasty to treat congenital aortic stenosis. METHODS: Seventy-five patients (median age: 8 years) underwent the procedure through the retrograde femoral or carotid route. RESULTS: The procedure was completed in 74 patients (98.6%). The peak-to-peak systolic gradient dropped from 79.6±27.7 to 22.3±17.8 mmHg (P<0.001), the left ventricular systolic pressure dropped from 164±39.1 to 110±24.8 mmHg (P<0.001), and the left ventricular end diastolic pressure dropped from 13.3±5.5 to 8.5±8.3 mmHg (P< 0.01). Four patients (5.3%) died due to the procedure. Aortic regurgitation (AoR) appeared or worsened in 27/71 (38%) patients, and no immediate surgical intervention was required. A mean follow-up of 50±38 months was obtained in 37 patients. Restenosis and significant AoR were observed in 16.6% of the patients. The estimates for being restenosis-free and for having significant AoR in 90 months were 60% and 50%, respectively. CONCLUSION: Aortic valvuloplasty was considered the initial palliative method of choice in managing congenital aortic stenosis, with satisfactory short- and midterm results.

Behavior of cardiac variables in animals exposed to cigarette smoke

OBJECTIVE: To assess the behavior of cardiac variables in animals exposed to cigarette smoke. METHODS: Two groups of Wistar rats were studied as follows: control group (C), comprising 28 animals; and smoking group (S), comprising 23 animals exposed to cigarette smoke for 30 days. Left ventricular cardiac function was assessed in vivo with transthoracic echocardiography, and myocardial performance was analyzed in vitro in preparations of isolated left ventricular papillary muscle. The cardiac muscle was assessed in isometric contractions with an extracellular calcium concentration of 2.5 mmol/L. RESULTS: No statistical difference was observed in the values of the body variables of the rats and in the mechanical data obtained from the papillary muscle between the control and smoking groups. The values of left ventricular systolic diameter were significantly greater in the smoking animals than in the control animals (C= 3.39 ± 0.4 mm and S= 3.71 ± 0.51 mm, P=0.02). A significant reduction was observed in systolic shortening fraction (C= 56.7 ± 4.2% and S= 53.5 ± 5.3%, P=0.02) and in ejection fraction (C= 0.92 ± 0.02 and S= 0.89 ± 0.04, P=0.01). CONCLUSION: The rats exposed to cigarette smoke had a reduction in left ventricular systolic function, although their myocardial function was preserved.

Gender-Based Differences in Cardiac Remodeling and ILK Expression after Myocardial Infarction

Background: Gender can influence post-infarction cardiac remodeling. Objective: To evaluate whether gender influences left ventricular (LV) remodeling and integrin-linked kinase (ILK) after myocardial infarction (MI). Methods: Female and male Wistar rats were assigned to one of three groups: sham, moderate MI (size: 20-39% of LV area), and large MI (size: ≥40% of LV area). MI was induced by coronary occlusion, and echocardiographic analysis was performed after six weeks to evaluate MI size as well as LV morphology and function. Real-time RT-PCR and Western blot were used to quantify ILK in the myocardium. Results: MI size was similar between genders. MI resulted in systolic dysfunction and enlargement of end-diastolic as well as end-systolic dimension of LV as a function of necrotic area size in both genders. Female rats with large MI showed a lower diastolic and systolic dilatation than the respective male rats; however, LV dysfunction was similar between genders. Gene and protein levels of ILK were increased in female rats with moderate and large infarctions, but only male rats with large infarctions showed an altered ILK mRNA level. A negative linear correlation was evident between LV dimensions and ILK expression in female rats with large MI. Conclusions: Post-MI ILK expression is altered in a gender-specific manner, and higher ILK levels found in females may be sufficient to improve LV geometry but not LV function.

Effects of Exercise Training on Heart Rate Variability in Chagas Heart Disease

Background: Heart rate variability (HRV) is a marker of autonomic dysfunction severity. The effects of physical training on HRV indexes in Chagas heart disease (CHD) are not well established. Objective: To evaluate the changes in HRV indexes in response to physical training in CHD. Methods: Patients with CHD and left ventricular (LV) dysfunction, physically inactive, were randomized either to the intervention (IG, N = 18) or control group (CG, N = 19). The IG participated in a 12-week exercise program consisting of 3 sessions/week. Results: Mean age was 49.5 ± 8 years, 59% males, mean LVEF was 36.3 ± 7.8%. Baseline HRV indexes were similar between groups. From baseline to follow-up, total power (TP): 1653 (IQ 625 - 3418) to 2794 (1617 - 4452) ms, p = 0.02) and very low frequency power: 586 (290 - 1565) to 815 (610 - 1425) ms, p = 0.047) increased in the IG, but not in the CG. The delta (post - pre) HRV indexes were similar: SDNN 11.5 ± 30.0 vs. 3.7 ± 25.1 ms. p = 0.10; rMSSD 2 (6 - 17) vs. 1 (21 - 9) ms. p = 0.43; TP 943 (731 - 3130) vs. 1780 (921 - 2743) Hz. p = 0.46; low frequency power (LFP) 1.0 (150 - 197) vs. 60 (111 - 146) Hz. p = 0.85; except for high frequency power, which tended to increase in the IG: 42 (133 - 92) vs. 79 (61 - 328) Hz. p = 0.08). Conclusion: In the studied population, the variation of HRV indexes was similar between the active and inactive groups. Clinical improvement with physical activity seems to be independent from autonomic dysfunction markers in CHD.