Neurovascular and hemodynamic responses to mental stress and exercise in severe COVID-19 survivors.

Previous studies show that COVID-19 survivors have elevated muscle sympathetic nerve activity (MSNA), endothelial dysfunction, and aortic stiffening. However, the neurovascular responses to mental stress and exercise are still unexplored. We hypothesized that COVID-19 survivors, compared with age- and body mass index (BMI)-matched control subjects, exhibit abnormal neurovascular responses to mental stress and physical exercise. Fifteen severe COVID-19 survivors (aged: 49 ± 2 yr, BMI: 30 ± 1 kg/m2) and 15 well-matched control subjects (aged: 46 ± 3 yr, BMI: 29 ± 1 kg/m2) were studied. MSNA (microneurography), forearm blood flow (FBF), and forearm vascular conductance (FVC, venous occlusion plethysmography), mean arterial pressure (MAP, Finometer), and heart rate (HR, ECG) were measured during a 3-min mental stress (Stroop Color-Word Test) and during a 3-min isometric handgrip exercise (30% of maximal voluntary contraction). During mental stress, MSNA (frequency and incidence) responses were higher in COVID-19 survivors than in controls (P < 0.001), and FBF and FVC responses were attenuated (P < 0.05). MAP was similar between the groups (P > 0.05). In contrast, the MSNA (frequency and incidence) and FBF and FVC responses to handgrip exercise were similar between the groups (P > 0.05). MAP was lower in COVID-19 survivors (P < 0.05). COVID-19 survivors exhibit an exaggerated MSNA and blunted vasodilatory response to mental challenge compared with healthy adults. However, the neurovascular response to handgrip exercise is preserved in COVID-19 survivors. Overall, the abnormal neurovascular control in response to mental stress suggests that COVID-19 survivors may have an increased risk to cardiovascular events during mental challenge.

Incidence and Predictors of Progression to Chagas Cardiomyopathy: Long-Term Follow-Up of Trypanosoma cruzi-Seropositive Individuals.

BACKGROUND: There are few contemporary cohorts of Trypanosoma cruzi-seropositive individuals, and the basic clinical epidemiology of Chagas disease is poorly understood. Herein, we report the incidence of cardiomyopathy and death associated with T. cruzi seropositivity. METHODS: Participants were selected in blood banks at 2 Brazilian centers. Cases were defined as T. cruzi-seropositive blood donors. T. cruzi-seronegative controls were matched for age, sex, and period of donation. Patients with established Chagas cardiomyopathy were recruited from a tertiary outpatient service. Participants underwent medical examination, blood collection, ECG, and echocardiogram at enrollment (2008-2010) and at follow-up (2018-2019). The primary outcomes were all-cause mortality and development of cardiomyopathy, defined as the presence of a left ventricular ejection fraction <50% or QRS complex duration ≥120 ms, or both. To handle loss to follow-up, a sensitivity analysis was performed using inverse probability weights for selection. RESULTS: We enrolled 499 T. cruzi-seropositive donors (age 48±10 years, 52% male), 488 T. cruzi-seronegative donors (age 49±10 years, 49% male), and 101 patients with established Chagas cardiomyopathy (age 48±8 years, 59% male). The mortality in patients with established cardiomyopathy was 80.9 deaths/1000 person-years (py) (54/101, 53%) and 15.1 deaths/1000 py (17/114, 15%) in T. cruzi-seropositive donors with cardiomyopathy at baseline. Among T. cruzi-seropositive donors without cardiomyopathy at baseline, mortality was 3.7 events/1000 py (15/385, 4%), which was no different from T. cruzi-seronegative donors with 3.6 deaths/1000 py (17/488, 3%). The incidence of cardiomyopathy in T. cruzi-seropositive donors was 13.8 (95% CI, 9.5-19.6) events/1000 py (32/262, 12%) compared with 4.6 (95% CI, 2.3-8.3) events/1000 py (11/277, 4%) in seronegative controls, with an absolute incidence difference associated with T. cruzi seropositivity of 9.2 (95% CI, 3.6-15.0) events/1000 py. T. cruzi antibody level at baseline was associated with development of cardiomyopathy (adjusted odds ratio, 1.4 [95% CI, 1.1-1.8]). CONCLUSIONS: We present a comprehensive description of the natural history of T. cruzi seropositivity in a contemporary patient population. The results highlight the central importance of anti-T. cruzi antibody titer as a marker of Chagas disease activity and risk of progression.

Effects of the association of diabetes and pulmonary emphysema on cardiac structure and function in rats.

Chronic obstructive pulmonary disease is often associated with chronic comorbid conditions of cardiovascular disease, diabetes mellitus and hypertension. This study aimed to investigate the effects of the association of diabetes and pulmonary emphysema on cardiac structure and function in rats. Wistar rats were divided into control non-diabetic instilled with saline (CS) or elastase (CE), diabetic instilled with saline (DS) or elastase (DE), DE treated with insulin (DEI) groups and echocardiographic measurements, morphometric analyses of the heart and lungs, and survival analysis conducted 50 days after instillation. Diabetes mellitus was induced [alloxan, 42 mg/kg, intravenously (iv)] 10 days before the induction of emphysema (elastase, 0.25 IU/100 g). Rats were treated with NPH insulin (4 IU before elastase plus 2 IU/day, 50 days). Both CE and DE exhibited similar increases in mean alveolar diameter, which are positively correlated with increases in right ventricular (RV) wall thickness (P = 0.0022), cavity area (P = 0.0001) and cardiomyocyte thickness (P = 0.0001). Diabetic saline group demonstrated a reduction in left ventricular (LV) wall, interventricular (IV) septum, cardiomyocyte thickness and an increase in cavity area, associated with a reduction in LV fractional shortening (P < 0.05), and an increase in LViv relaxation time (P < 0.05). Survival rate decreased from 80% in DS group to 40% in DE group. In conclusion, alloxan diabetes did not affect RV hypertrophy secondary to chronic emphysema, even in the presence of insulin. Diabetes per se induced left ventricular dysfunction, which was less evident in the presence of RV hypertrophy. Survival rate was substantially reduced as a consequence, at least in part, of the coexistence of RV hypertrophy and diabetic cardiomyopathy.

Ten-year incidence of Chagas cardiomyopathy among asymptomatic Trypanosoma cruzi-seropositive former blood donors.

BACKGROUND: Very few studies have measured disease penetrance and prognostic factors of Chagas cardiomyopathy among asymptomatic Trypanosoma cruzi-infected persons. METHODS AND RESULTS: We performed a retrospective cohort study among initially healthy blood donors with an index T cruzi-seropositive donation and age-, sex-, and period-matched seronegatives in 1996 to 2002 in the Brazilian cities of São Paulo and Montes Claros. In 2008 to 2010, all subjects underwent medical history, physical examination, ECGs, and echocardiograms. ECG and echocardiogram results were classified by blinded core laboratories, and records with abnormal results were reviewed by a blinded panel of 3 cardiologists who adjudicated the outcome of Chagas cardiomyopathy. Associations with Chagas cardiomyopathy were tested with multivariate logistic regression. Mean follow-up time between index donation and outcome assessment was 10.5 years for the seropositives and 11.1 years for the seronegatives. Among 499 T cruzi seropositives, 120 (24%) had definite Chagas cardiomyopathy, and among 488 T cruzi seronegatives, 24 (5%) had cardiomyopathy, for an incidence difference of 1.85 per 100 person-years attributable to T cruzi infection. Of the 120 seropositives classified as having Chagas cardiomyopathy, only 31 (26%) presented with ejection fraction <50%, and only 11 (9%) were classified as New York Heart Association class II or higher. Chagas cardiomyopathy was associated (P<0.01) with male sex, a history of abnormal ECG, and the presence of an S3 heart sound. CONCLUSIONS: There is a substantial annual incidence of Chagas cardiomyopathy among initially asymptomatic T cruzi-seropositive blood donors, although disease was mild at diagnosis.

Sympathetic Neural Overdrive, Aortic Stiffening, Endothelial Dysfunction, and Impaired Exercise Capacity in Severe COVID-19 Survivors: A Mid-Term Study of Cardiovascular Sequelae.

BACKGROUND: COVID-19 has become a dramatic health problem during this century. In addition to high mortality rate, COVID-19 survivors are at increased risk for cardiovascular diseases 1-year after infection. Explanations for these manifestations are still unclear but can involve a constellation of biological alterations. We hypothesized that COVID-19 survivors compared with controls exhibit sympathetic overdrive, vascular dysfunction, cardiac morpho-functional changes, impaired exercise capacity, and increased oxidative stress. METHODS: Nineteen severe COVID-19 survivors and 19 well-matched controls completed the study. Muscle sympathetic nerve activity (microneurography), brachial artery flow-mediated dilation and blood flow (Doppler-Ultrasound), carotid-femoral pulse wave velocity (Complior), cardiac morpho-functional parameters (echocardiography), peak oxygen uptake (cardiopulmonary exercise testing), and oxidative stress were measured ~3 months after hospital discharge. Complementary experiments were conducted on human umbilical vein endothelial cells cultured with plasma samples from subjects. RESULTS: Muscle sympathetic nerve activity and carotid-femoral pulse wave velocity were greater and brachial artery flow-mediated dilation, brachial artery blood flow, E/e' ratio, and peak oxygen uptake were lower in COVID-19 survivors than in controls. COVID-19 survivors had lower circulating antioxidant markers compared with controls, but there were no differences in plasma-treated human umbilical vein endothelial cells nitric oxide production and reactive oxygen species bioactivity. Diminished peak oxygen uptake was associated with sympathetic overdrive, vascular dysfunction, and reduced diastolic function in COVID-19 survivors. CONCLUSIONS: Our study revealed that COVID-19 survivors have sympathetic overactivation, vascular dysfunction, cardiac morpho-functional changes, and reduced exercise capacity. These findings indicate the need for further investigation to determine whether these manifestations are persistent longer-term and their impact on the cardiovascular health of COVID-19 survivors.

Changes in cardiac heparan sulfate proteoglycan expression and streptozotocin-induced diastolic dysfunction in rats.

BACKGROUND: Changes in the proteoglycans glypican and syndecan-4 have been reported in several pathological conditions, but little is known about their expression in the heart during diabetes. The aim of this study was to investigate in vivo heart function changes and alterations in mRNA expression and protein levels of glypican-1 and syndecan-4 in cardiac and skeletal muscles during streptozotocin (STZ)-induced diabetes. METHODS: Diabetes was induced in male Wistar rats by STZ administration. The rats were assigned to one of the following groups: control (sham injection), after 24 hours, 10 days, or 30 days of STZ administration. Echocardiography was performed in the control and STZ 10-day groups. Western and Northern blots were used to quantify protein and mRNA levels in all groups. Immunohistochemistry was performed in the control and 30-day groups to correlate the observed mRNA changes to the protein expression. RESULTS: In vivo cardiac functional analysis performed using echocardiography in the 10-day group showed diastolic dysfunction with alterations in the peak velocity of early (E) diastolic filling and isovolumic relaxation time (IVRT) indices. These functional alterations observed in the STZ 10-day group correlated with the concomitant increase in syndecan-4 and glypican-1 protein expression. Cardiac glypican-1 mRNA and skeletal syndecan-4 mRNA and protein levels increased in the STZ 30-day group. On the other hand, the amount of glypican in skeletal muscle was lower than that in the control group. The same results were obtained from immunohistochemistry analysis. CONCLUSION: Our data suggest that membrane proteoglycans participate in the sequence of events triggered by diabetes and inflicted on cardiac and skeletal muscles.

Effects of sympathectomy on myocardium remodeling and function.

OBJECTIVES: To evaluate the effects of sympathectomy on the myocardium in an experimental model. METHODS: The study evaluated three groups of male Wistar rats: control (CT; n=15), left unilateral sympathectomy (UNI; n=15), and bilateral sympathectomy (BIL; n=31). Sympathectomy was performed by injection of absolute alcohol into the space of the spinous process of the C7 vertebra. After 6 weeks, we assessed the chronotropic properties at rest and stress, cardiovascular autonomic modulation, myocardial and peripheral catecholamines, and beta-adrenergic receptors in the myocardium. The treadmill test consisted of an escalated protocol with a velocity increment until the maximal velocity tolerated by the animal was reached. RESULTS: The bilateral group had higher levels of peripheral catecholamines, and consequently, a higher heart rate (HR) and blood pressure levels. This suggests that the activation of a compensatory pathway in this group may have deleterious effects. The BIL group had basal tachycardia immediately before the exercise test and increased tachycardia at peak exercise (p<0.01); the blood pressure had the same pattern (p=0.0365). The variables related to autonomic modulation were not significantly different between groups, with the exception of the high frequency (HF) variable, which showed significant differences in CT vs UNI. There was no significant difference in beta receptor expression between groups. There was a higher concentration of peripheral norepinephrine in the BIL group (p=0.0001), and no significant difference in myocardial norepinephrine (p=0.09). CONCLUSION: These findings suggest that an extra cardiac compensatory pathway increases the sympathetic tonus and maintains a higher HR and higher levels of peripheral catecholamines in the procedure groups. The increase in HF activity can be interpreted as an attempt to increase the parasympathetic tonus to balance the greater sympathetic activity.

Early changes in myocyte contractility and cardiac function in streptozotocin-induced type 1 diabetes in rats.

Diabetes can elicit direct deleterious effects on the myocardium, independent of coronary artery disease or hypertension. These cardiac disturbances are termed diabetic cardiomyopathy showing increased risk of heart failure with or without reduced ejection fraction. Presently, there is no specific treatment for this type of cardiomyopathy and in the case of type I diabetes, it may start in early childhood independent of glycemic control. We hypothesized that alterations in isolated myocyte contractility and cardiac function are present in the early stages of experimental diabetes in rats before overt changes in myocardium structure occur. Diabetes was induced by single-dose injection of streptozotocin (STZ) in rats with data collected from control and diabetic animals 3 weeks after injection. Left ventricle myocyte contractility was measured by single-cell length variation under electrical stimulation. Cardiac function and morphology were studied by high-resolution echocardiography with pulsed-wave tissue Doppler imaging (TDI) measurements and three-lead surface electrocardiogram. Triglycerides, cholesterol and liver enzyme levels were measured from plasma samples obtained from both groups. Myocardial collagen content and perivascular fibrosis of atria and ventricle were studied by histological analysis after picrosirius red staining. Diabetes resulted in altered contractility of isolated cardiac myocytes with increased contraction and relaxation time intervals. Echocardiography showed left atrium dilation, increased end-diastolic LV and posterior wall thickness, with reduced longitudinal systolic peak velocity (S') of the septum mitral annulus at the apical four-chamber view obtained by TDI. Triglycerides, aspartate aminotransferase and alkaline phosphatase were elevated in diabetic animals. Intertitial collagen content was higher in atria of both groups and did not differ among control and diabetic animals. Perivascular intramyocardial arterioles collagen did not differ between groups. These results suggest that alterations in cardiac function are present in the early phase in this model of diabetes type 1 and occur before overt changes in myocardium structure appear as evaluated by intersticial collagen deposition and perivascular fibrosis of intramyocardial arterioles.

Echocardiographic predictors of functional capacity in endomyocardial fibrosis patients.

AIMS: Endomyocardial fibrosis (EMF) is a restrictive cardiomyopathy manifested mainly by diastolic heart failure. It is recognized that diastole is an important determinant of exercise capacity. The purpose of this study was to determine whether resting echocardiographic parameters might predict oxygen consumption (VO(2p)) by ergoespirometry and the prognostic role of functional capacity in EMF patients. METHODS AND RESULTS: A total of 32 patients with biventricular EMF (29 women, 55.3 +/- 11.4 years) were studied by echocardiography and ergoespirometry. The relationship between the echocardiographic indexes and the percentage of predicted VO(2p) (%VO(2p)) was investigated by the 'stepwise' linear regression analysis. The median VO(2p) was 11 +/- 3 mL/kg/min and the %VO(2p) was 53 +/- 9%. There was a correlation of %VO(2p) with an average of A' at four sites of the mitral annulus (A' peak, r = 0.471, P = 0.023), E'/A' of the inferior mitral annulus (r = -0.433, P = 0.044), and myocardial performance index (r = -0.352, P = 0.048). On multiple regression analysis, only A' peak was an independent predictor of %VO(2p) (%VO(2p)= 26.34 + 332.44 x A' peak). EMF patients with %VO(2p)< 53% had an increased mortality rate with a relative risk of 8.47. CONCLUSION: In EMF patients, diastolic function plays an important role in determining the limitations to exercise and %VO(2p) has a prognostic value.

Exercise Rehabilitation Improves Cardiac Volumes and Functional Capacity in Patients With Endomyocardial Fibrosis: A RANDOMIZED CONTROLLED TRIAL.

PURPOSE: Endomyocardial fibrosis (EMF) is a restrictive cardiomyopathy associated with low functional capacity and high mortality rates. Exercise training has been proved to be a nonpharmacological treatment of cardiovascular diseases. Therefore, the purpose of this study was to determine the effects of exercise rehabilitation in EMF patients. METHODS: Twenty-two EMF patients, functional classes II and III (New York Heart Association [NYHA]), were randomized to the control (C-EMF) or exercise rehabilitation (Rehab-EMF) group. Patients in the Rehab-EMF group underwent 4 mo of exercise rehabilitation, whereas patients in the C-EMF group were instructed to maintain their usual daily routine. Peak oxygen uptake ((Equation is included in full-text article.)O2), cardiac function, and quality of life were evaluated. All assessments were performed at baseline and after 4 mo. RESULTS: After 4 mo of rehabilitation, peak (Equation is included in full-text article.)O2 increased in the Rehab-EMF group (17.4 ± 3.0 to 19.7 ± 4.4 mL/kg/min, P < .001), whereas the C-EMF group showed no difference (15.3 ± 3.0 to 15.0 ± 2.0 mL/kg/min, P = .87). Also, post-intervention, peak (Equation is included in full-text article.)O2 in the Rehab-EMF group was greater than that in the C-EMF group (P < .001). Furthermore, the Rehab-EMF group, when compared to the C-EMF group, showed an increase in left ventricular end-diastolic volume (102.1 ± 64.6 to 136.2 ± 75.8 mL vs 114.4 ± 55.0 to 100.4 ± 49.9 mL, P < .001, respectively) and decrease in left atrial diastolic volume (69.0 ± 33.0 to 34.9 ± 15.0 mL vs 44.6 ± 21.0 to 45.6 ± 23.0 mL, P < .001, respectively). Quality-of-life scores also improved in the Rehab-EMF group, whereas the C-EMF group showed no change (45 ± 23 to 27 ± 15 vs 47 ± 15 to 45 ± 17, P < .001, respectively). CONCLUSION: Exercise rehabilitation is a nonpharmacological intervention that improves functional capacity, cardiac volumes, and quality of life in EMF patients after endocardial resection surgery. In addition, exercise rehabilitation should be prescribed to EMF patients to improve their clinical condition.

Myocardial T1 mapping and extracellular volume quantification in patients with left ventricular non-compaction cardiomyopathy.

Aims: From pathophysiological mechanisms to risk stratification and management, much debate and discussion persist regarding left ventricular non-compaction cardiomyopathy (LVNC). This study aimed to characterize myocardial T1 mapping and extracellular volume (ECV) fraction by cardiovascular magnetic resonance (CMR), and investigate how these biomarkers relate to left ventricular ejection fraction (LVEF) and ventricular arrhythmias (VA) in LVNC. Methods and results: Patients with LVNC (n = 36) and healthy controls (n = 18) were enrolled to perform a CMR with T1 mapping. ECV was quantified in LV segments without late gadolinium enhancement (LGE) areas to investigate diffuse myocardial fibrosis. Patients with LVNC had slightly higher native T1 (1024 ± 43 ms vs. 995 ± 22 ms, P = 0.01) and substantially expanded ECV (28.0 ± 4.5% vs. 23.5 ± 2.2%, P < 0.001) compared to controls. The ECV was independently associated with LVEF (ß = -1.3, P = 0.001). Among patients without LGE, VAs were associated with higher ECV (27.7% with VA vs. 25.8% without VA, P = 0.002). Conclusion: In LVNC, tissue characterization by T1 mapping suggests an extracellular expansion by diffuse fibrosis in myocardium without LGE, which was associated with myocardial dysfunction and VA, but not with the amount of non-compacted myocardium.

The Expression of Lipoprotein Receptors Is Increased in the Infarcted Area After Myocardial Infarction Induced in Rats With Cardiac Dysfunction.

Left ventricular (LV) remodeling after myocardial infarction constitutes the structural basis for ventricular dysfunction and heart failure. The characterization underlying the expression of lipoprotein receptors in cardiac dysfunction is scarcely explored. The aim of this study was to analyze the status of lipoprotein receptors on the infarcted and noninfarcted areas of LV and to verify whether nanoparticles that mimic the lipid structure of low-density lipoprotein (LDL) and have the ability to bind to LDL receptors (LDE) are taken up more avidly by the noninfarcted LV. 13 male Wistar rats with left coronary artery ligation (myocardial infarction [MI]) and 12 animals with SHAM operation (SHAM) were used in this study. 6 weeks after the procedure, the quantification of low-density lipoprotein receptor (LDLR), LDL receptor-related protein 1 (LRP1), scavenger receptor-class B type I (SR-BI) lipoprotein receptors, and PCNA proliferation marker, and tissue uptake of radioactively labeled LDE were performed. Immunohistochemistry and Western blot analysis showed that LDLR, LRP1, SR-BI, and PCNA, expression in infarcted area of MI was remarkably higher than SHAM and noninfarcted subendocardial (SEN) and interstitial (INT) areas. In addition, in SEN noninfarcted area of MI, the presence of LDLR was about threefold higher than in SHAM SEN and INT noninfarcted areas. The LDE uptake of noninfarcted LV of MI group was about 30% greater than that of SHAM group. In conclusion, these findings regarding the status of lipoprotein receptors after MI induction could help to establish mechanisms on myocardial repairing. In conclusion, infarcted rats with LV dysfunction showed increased expression of lipoprotein receptors mainly in the infarcted area.

The Effects of Diabetes Induction on the Rat Heart: Differences in Oxidative Stress, Inflammatory Cells, and Fibrosis between Subendocardial and Interstitial Myocardial Areas.

Diabetic cardiomyopathy (DCM) is characterized by cardiac remodeling and impaired diastolic function that may lead to heart failure. The aim of this study was to evaluate oxidative stress, inflammatory cells, and fibrosis in both subendocardial (SEN) and interstitial (INT) areas of the myocardium. Male Wistar rats were allocated to 2 groups of 9 animals, a control (CT) group and streptozotocin-induced diabetes (DM). After 8 weeks, echocardiography morphometry, protein expression, and confocal microscopy in SEN and INT areas of the left ventricle (LV) were performed. The echocardiographic analysis showed that diabetes induction leads to cardiac dilation, hypertrophy, and LV diastolic dysfunction. As compared to CT, the induction of diabetes increased inflammatory cells and fibrosis in both SEN and INT areas of DM myocardium and increased ROS generation only in SEN. Comparing the SEN and INT areas in the DM group, inflammatory cells and fibrosis in SEN were greater than in INT. In conclusion, diabetic myocardium SEN area, wherein oxidative stress was more pronounced, is more susceptible to cardiac dysfunction than INT area. This finding can be important for the understanding of the heart remodeling process occurring in DCM and perhaps to engender targeted therapies to attenuate or revert DCM-related diastolic dysfunction.

Characterization of Cardiopulmonary Exercise Testing Variables in Patients with Endomyocardial Fibrosis after Endocardial Resection.

BACKGROUND: Endomyocardial fibrosis (EMF) is a rare disease, characterized by diastolic dysfunction which leads to reduced peak oxygen consumption (VO2). Cardiopulmonary exercise testing (CPET) has been proved to be a fundamental tool to identify central and peripheral alterations. However, most studies prioritize peak VO2 as the main variable, leaving aside other important CPET variables that can specify the severity of the disease and guide the clinical treatment. OBJECTIVE: The aim of this study was to evaluate central and peripheral limitations in symptomatic patients with EMF by different CPET variables. METHODS: Twenty-six EMF patients (functional class III, NYHA) were compared with 15 healthy subjects (HS). Functional capacity was evaluated using CPET and diastolic and systolic functions were evaluated by echocardiography. RESULTS: Age and gender were similar between EMF patients and HS. Left ventricular ejection fraction was normal in EMF patients, but decreased compared to HS. Peak heart rate, peak workload, peak VO2, peak oxygen (O2) pulse and peak pulmonary ventilation (VE) were decreased in EMF compared to HS. Also, EMF patients showed increased Δ heart rate /Δ oxygen uptake and Δ oxygen uptake /Δ work rate compared to HS. CONCLUSION: Determination of the aerobic capacity by noninvasive respiratory gas exchange during incremental exercise provides additional information about the exercise tolerance in patients with EMF. The analysis of different CPET variables is necessary to help us understand more about the central and peripheral alterations cause by both diastolic dysfunction and restrictive pattern.

Cardiac and peripheral autonomic control in restrictive cardiomyopathy.

AIMS: Autonomic dysfunction determines the advance of dilated cardiomyopathy (DCM) and is related to poor outcomes. However, this autonomic imbalance is unknown in patients with restrictive cardiomyopathy (RCM) even though they have similar symptoms and poor quality of life as DCM patients have. The aim of this study was to evaluate if autonomic and neurovascular controls were altered in RCM patients. METHODS AND RESULTS: Fifteen RCM patients, 10 DCM patients, and 10 healthy subjects were evaluated. Heart rate and blood pressure (BP) were recorded. Peripheral sympathetic activity [muscle sympathetic nerve activity (MSNA)] by microneurography and cardiac sympathetic activity by power spectrum analysis of heart rate variability. Spontaneous baroreflex sensitivity (BRS) was evaluated by the sequence method and forearm blood flow by venous occlusion plethysmography. Both cardiomyopathy groups had higher MSNA frequency (P < 0.001) and MSNA incidence (P < 0.001), higher cardiac sympathovagal balance (P < 0.02), reduced BRS for increase (P = 0.002) and for decrease in BP (P = 0.002), and lower forearm blood flow (P < 0.001) compared with healthy subjects. We found an inverse correlation between BRS for increase and decrease in BP and peripheral sympathetic activity (r = -0.609, P = 0.001 and r = -0.648, P < 0.001, respectively) and between BRS for increase and decrease in BP and cardiac sympathetic activity (r = -0.503, P = 0.03 and r = -0.487, P = 0.04, respectively). CONCLUSIONS: The RCM patients had cardiac and peripheral autonomic dysfunctions associated with peripheral vasoconstriction. Nonetheless, the presence of normal ejection fraction underestimates the evolution of the disease and makes clinical treatment difficult. These alterations could lead to a similar cardiovascular risk as that observed in DCM patients.

Aldosterone antagonism in an inflammatory state: evidence for myocardial protection.

INTRODUCTION: Chagas' disease is one of the most important causes of dilated cardiomyopathy in South and Central America. It is an inflammatory cardiomyopathy. We wanted to investigate whether it could have the same response to aldosterone antagonism as demonstrated before in other dilated cardiomyopathies. OBJECTIVE: To evaluate the role of spironolactone in myocardial remodelling in a Chagas cardiomyopathy model. MATERIAL AND METHODS: We studied 60 Sirius Hamsters divided into: control (C) infected (Inf) and Inf plus spironolactone (Infsp, 40 mg/kg/day) groups, for 11 months. Echocardiography with colour doppler was performed. Left ventricular end diastolic diameter (LVEDD), fractional shortening (FS) and corrected isovolumic relaxation time (IRT) were evaluated, as well as interstitial collagen volume fraction (ICVF) and myocardial inflammation. RESULT: The results demonstrated that survival was improved by use of spironolactone in the chronic phase (p<0.04). Body weight (BW) was C:190 g, Inf:167 g*, Infsp:198 g (*p<0.05, compared to C and Infsp), LVEDD/BW was C:0.31, Inf: 0.35*, Infsp: 0.29 (*p<0.05, compared to C and Infsp), FS was C:38, Inf: 35.5, Infsp: 38 (with no statistical difference) and IRT was C: 23 msec, Inf: 26 msec*, Infsp: 22 msec (p<0.05, compared to C and Infsp). ICVF (%) was attenuated at LV (C: 0.34+/-0.1, Inf: 1.75+/-0.7*, Infsp: 0.95+/-0.2*; *p<0.05, p<0.05). CONCLUSION: Spironolactone attenuated the myocardial remodelling in Chagas cardiomyopathy, reduced mortality during the chronic phase and reduced inflammatory infiltration.

[NT pro-BNP levels in pericardial diseases and how they are used as complementary evaluation method of diastolic restriction. Initial experience: 25 cases]. / Dosagem dos níveis de NT pro-BNP nas afecções pericárdicas e sua utilidade como método complementar de avaliação de restrição diastólica. Experiência inicial de 25 casos.

OBJECTIVE: To determine whether NT pro-BNP levels are high in patients reporting pericardial diseases, as well as to investigate how they relate to diastolic dysfunction echocardiographic measures. METHODS: Twenty-five patients were split into two groups: 1) pericardial effusion (PE): 15 patients; 2) constrictive pericarditis (CP): 10 patients. A control group was made up with 30 individuals reporting no heart disease. Pericardial effusion was evaluated by bidimensional echocardiogram, with restriction evaluated by pulsed Doppler of mitral flow. CP diagnosis was confirmed by MRI. NT pro-BNP levels were measured by immunoassay and detected by electrochemiluminescence. RESULTS: From the 15 PD patients, 14 reported relevant PD, and only 1, moderate PD. Log NT pro-BNP was shown to be higher in PD (p < 0.05), with log mean of 2.31 pg/ml and CP (p < 0.05), with log mean of 2.67 pg/ml, when compared to control group, log mean of 1.32 pg/ml. No difference was reported between PD and CP (p = 0.149). The NT pro-BNP log showed to be correlated to peak velocity of the E wave (r = 0.845; p = 0.001) and with E/A (r = 0.717; p = 0.003). CONCLUSION: NT pro-BNP is shown to have increased in pericardial diseases, and is associated to diastolic dysfunction. It may serve as an additional method in quantifying restriction.

Impact of aging on cardiac function in a female rat model of menopause: role of autonomic control, inflammation, and oxidative stress.

OBJECTIVE: The aim of this study was to evaluate the effects of aging on metabolic, cardiovascular, autonomic, inflammatory, and oxidative stress parameters after ovarian hormone deprivation (OVX). METHODS: Female Wistar rats (3 or 22 months old) were divided into: young controls, young ovariectomized, old controls, and old ovariectomized (bilateral ovaries removal). After a 9-week follow-up, physical capacity, metabolic parameters, and morphometric and cardiac functions were assessed. Subsequently, arterial pressure was recorded and cardiac autonomic control was evaluated. Oxidative stress was measured on the cardiac tissue, while inflammatory profile was assessed in the plasma. RESULTS: Aging or OVX caused an increase in body and fat weight and triglyceride concentration and a decrease in both insulin sensitivity and aerobic exercise capacity. Left ventricular diastolic dysfunction and increased cardiac overload (myocardial performance index) were reported in old groups when compared with young groups. Aging and OVX led to an increased sympathetic tonus, and vagal tonus was lower only for the old groups. Tumor necrosis factor-α and interleukin-6 were increased in old groups when compared with young groups. Glutathione redox balance (GSH/GSSG) was reduced in young ovariectomized, old controls, and old ovariectomized groups when compared with young controls, indicating an increased oxidative stress. A negative correlation was found between GSH/GSSG and tumor necrosis factor-α (r=-0.6, P<0.003). Correlations were found between interleukin-6 with adipose tissue (r=0.5, P<0.009) and vagal tonus (r=-0.7, P<0.0002); and among myocardial performance index with interleukin-6 (r=0.65, P<0.0002), sympathetic tonus (r=0.55, P<0.006), and physical capacity (r=-0.55, P<0.003). The findings in this trial showed that ovariectomy aggravated the impairment of cardiac and functional effects of aging in female rats, probably associated with exacerbated autonomic dysfunction, inflammation, and oxidative stress.

Acute Effects of Nasal CPAP in Patients With Hypertrophic Cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a common genetic disease that may cause left ventricular outflow tract (LVOT) obstruction, heart failure, and sudden death. Recent studies have shown a high prevalence of OSA among patients with HCM. Because the hemodynamics in patients with LVOT obstruction are unstable and depend on the loading conditions of the heart, we evaluated the acute effects of CPAP on hemodynamics and cardiac performance in patients with HCM. METHODS: We studied 26 stable patients with HCM divided into nonobstructive HCM (n = 12) and obstructive HCM (n = 14) groups (LVOT gradient pressure lower or higher than 30 mm Hg, respectively). Patients in the supine position while awake were continuously monitored with beat-to-beat BP measurements and electrocardiography. Two-dimensional echocardiography was performed at rest (baseline) and after 20 min of nasal CPAP at 1.5 cm H2O and 10 cm H2O, which was applied in a random order interposed by 10 min without CPAP. RESULTS: BP, cardiac output, stroke volume, heart rate, left ventricular ejection fraction, and LVOT gradient did not change during the study period in either group. CPAP at 10 cm H2O decreased right atrial size and right ventricular relaxation in all patients. It also decreased left atrial volume significantly and decreased right ventricular outflow acceleration time, suggesting an increase in pulmonary artery pressure in patients with obstructive HCM. CONCLUSIONS: The acute application of CPAP is apparently safe in patients with HCM, because CPAP does not lead to hemodynamic compromise. Long-term studies in patients with HCM and sleep apnea and nocturnal CPAP are warranted. TRIAL REGISTRY: ClinicalTrials.gov; No. NCT01631006; URL: www.clinicaltrials.gov.