Abnormal neurovascular control during central and peripheral chemoreceptors stimulation in heart failure patients with preserved ejection fraction.

PURPOSE: Central and peripheral chemoreceptors are hypersensitized in patients with heart failure with reduced ejection fraction. Whether this autonomic alteration occurs in patients with heart failure with preserved ejection fraction (HFpEF) remains little known. We test the hypothesis that the central and peripheral chemoreflex control of muscle sympathetic nerve activity (MSNA) is altered in HFpEF. METHODS: Patients aged 55-80 years with symptoms of heart failure, body mass index ≤ 35 kg/m2, left ventricular ejection fraction > 50%, left atrial volume index > 34 mL/m2, left ventricular early diastolic filling velocity and early diastolic tissue velocity of mitral annulus ratio (E/e' index) ≥ 13, and BNP levels > 35 pg/mL were included in the study (HFpEF, n = 9). Patients without heart failure with preserved ejection fraction (non-HFpEF, n = 9), aged-paired, were also included in the study. Peripheral chemoreceptors stimulation (10% O2 and 90% N2, with CO2 titrated) and central chemoreceptors stimulation (7% CO2 and 93% O2) were conducted for 3 min. MSNA was evaluated by microneurography technique, and forearm blood flow (FBF) by venous occlusion plethysmography. RESULTS: During hypoxia, MSNA responses were greater (p < 0.001) and FBF responses were lower in patients with HFpEF (p = 0.006). Likewise, MSNA responses during hypercapnia were higher (p < 0.001) and forearm vascular conductance (FVC) levels were lower (p = 0.030) in patients with HFpEF. CONCLUSIONS: Peripheral and central chemoreflex controls of MSNA are hypersensitized in patients with HFpEF, which seems to contribute to the increase in MSNA in these patients. In addition, peripheral and central chemoreceptors stimulation in patients with HFpEF causes muscle vasoconstriction.

Exercise Ventilation in COPD: Influence of Systolic Heart Failure.

Systolic heart failure is a common and disabling co-morbidity of chronic obstructive pulmonary disease (COPD) which may increase exercise ventilation due to heightened neural drive and/or impaired pulmonary gas exchange efficiency. The influence of heart failure on exercise ventilation, however, remains poorly characterized in COPD. In a prospective study, 98 patients with moderate to very severe COPD [41 with coexisting heart failure; 'overlap' (left ventricular ejection fraction < 50%)] underwent an incremental cardiopulmonary exercise test (CPET). Compared to COPD, overlap had lower peak exercise capacity despite higher FEV1. Overlap showed lower operating lung volumes, greater ventilatory inefficiency and larger decrements in end-tidal CO2 (PETCO2) (P < 0.05). These results were consistent with those found in FEV1-matched patients. Larger areas under receiver operating characteristic curves to discriminate overlap from COPD were found for ventilation ([Formula: see text]E)-CO2 output [Formula: see text]CO2) intercept, [Formula: see text]E-[Formula: see text]CO2 slope, peak [Formula: see text]E/[Formula: see text]CO2 ratio and peak PETCO2. Multiple logistic regression analysis revealed that [Formula: see text]CO2 intercept ≤ 3.5 L/minute [odds ratios (95% CI) = 7.69 (2.61-22.65), P < 0.001] plus [Formula: see text]E-[Formula: see text]CO2 slope ≥ 34 [2.18 (0.73-6.50), P = 0.14] or peak [Formula: see text]E/[Formula: see text]CO2 ratio ≥ 37 [5.35 (1.96-14.59), P = 0.001] plus peak PETCO2 ≤ 31 mmHg [5.73 (1.42-23.15), P = 0.01] were indicative of overlapping. Heart failure increases the ventilatory response to metabolic demand in COPD. Variables reflecting excessive ventilation might prove useful to assist clinical interpretation of CPET responses in COPD patients presenting heart failure as co-morbidity.

Exercise training prevents the deterioration in the arterial baroreflex control of sympathetic nerve activity in chronic heart failure patients.

Arterial baroreflex control of muscle sympathetic nerve activity (ABRMSNA) is impaired in chronic systolic heart failure (CHF). The purpose of the study was to test the hypothesis that exercise training would improve the gain and reduce the time delay of ABRMSNA in CHF patients. Twenty-six CHF patients, New York Heart Association Functional Class II-III, EF ≤ 40%, peak V̇o2 ≤ 20 ml·kg(-1)·min(-1) were divided into two groups: untrained (UT, n = 13, 57 ± 3 years) and exercise trained (ET, n = 13, 49 ± 3 years). Muscle sympathetic nerve activity (MSNA) was directly recorded by microneurography technique. Arterial pressure was measured on a beat-to-beat basis. Time series of MSNA and systolic arterial pressure were analyzed by autoregressive spectral analysis. The gain and time delay of ABRMSNA was obtained by bivariate autoregressive analysis. Exercise training was performed on a cycle ergometer at moderate intensity, three 60-min sessions per week for 16 wk. Baseline MSNA, gain and time delay of ABRMSNA, and low frequency of MSNA (LFMSNA) to high-frequency ratio (HFMSNA) (LFMSNA/HFMSNA) were similar between groups. ET significantly decreased MSNA. MSNA was unchanged in the UT patients. The gain and time delay of ABRMSNA were unchanged in the ET patients. In contrast, the gain of ABRMSNA was significantly reduced [3.5 ± 0.7 vs. 1.8 ± 0.2, arbitrary units (au)/mmHg, P = 0.04] and the time delay of ABRMSNA was significantly increased (4.6 ± 0.8 vs. 7.9 ± 1.0 s, P = 0.05) in the UT patients. LFMSNA-to-HFMSNA ratio tended to be lower in the ET patients (P < 0.08). Exercise training prevents the deterioration of ABRMSNA in CHF patients.

Molecular basis for the improvement in muscle metaboreflex and mechanoreflex control in exercise-trained humans with chronic heart failure.

Previous studies have demonstrated that muscle mechanoreflex and metaboreflex controls are altered in heart failure (HF), which seems to be due to changes in cyclooxygenase (COX) pathway and changes in receptors on afferent neurons, including transient receptor potential vanilloid type-1 (TRPV1) and cannabinoid receptor type-1 (CB1). The purpose of the present study was to test the hypotheses: 1) exercise training (ET) alters the muscle metaboreflex and mechanoreflex control of muscle sympathetic nerve activity (MSNA) in HF patients. 2) The alteration in metaboreflex control is accompanied by increased expression of TRPV1 and CB1 receptors in skeletal muscle. 3) The alteration in mechanoreflex control is accompanied by COX-2 pathway in skeletal muscle. Thirty-four consecutive HF patients with ejection fractions <40% were randomized to untrained (n = 17; 54 ± 2 yr) or exercise-trained (n = 17; 56 ± 2 yr) groups. MSNA was recorded by microneurography. Mechanoreceptors were activated by passive exercise and metaboreceptors by postexercise circulatory arrest (PECA). COX-2 pathway, TRPV1, and CB1 receptors were measured in muscle biopsies. Following ET, resting MSNA was decreased compared with untrained group. During PECA (metaboreflex), MSNA responses were increased, which was accompanied by the expression of TRPV1 and CB1 receptors. During passive exercise (mechanoreflex), MSNA responses were decreased, which was accompanied by decreased expression of COX-2, prostaglandin-E2 receptor-4, and thromboxane-A2 receptor and by decreased in muscle inflammation, as indicated by increased miRNA-146 levels and the stable NF-κB/IκB-α ratio. In conclusion, ET alters muscle metaboreflex and mechanoreflex control of MSNA in HF patients. This alteration with ET is accompanied by alteration in TRPV1 and CB1 expression and COX-2 pathway and inflammation in skeletal muscle.

Sildenafil improves microvascular O2 delivery-to-utilization matching and accelerates exercise O2 uptake kinetics in chronic heart failure.

Nitric oxide (NO) can temporally and spatially match microvascular oxygen (O(2)) delivery (Qo(2mv)) to O(2) uptake (Vo(2)) in the skeletal muscle, a crucial adjustment-to-exercise tolerance that is impaired in chronic heart failure (CHF). To investigate the effects of NO bioavailability induced by sildenafil intake on muscle Qo(2mv)-to-O(2) utilization matching and Vo(2) kinetics, 10 males with CHF (ejection fraction = 27 ± 6%) undertook constant work-rate exercise (70-80% peak). Breath-by-breath Vo(2), fractional O(2)extraction in the vastus lateralis {∼deoxygenated hemoglobin + myoglobin ([deoxy-Hb + Mb]) by near-infrared spectroscopy}, and cardiac output (CO) were evaluated after sildenafil (50 mg) or placebo. Sildenafil increased exercise tolerance compared with placebo by ∼20%, an effect that was related to faster on- and off-exercise Vo(2) kinetics (P < 0.05). Active treatment, however, failed to accelerate CO dynamics (P > 0.05). On-exercise [deoxy-Hb + Mb] kinetics were slowed by sildenafil (∼25%), and a subsequent response "overshoot" (n = 8) was significantly lessened or even abolished. In contrast, [deoxy-Hb + Mb] recovery was faster with sildenafil (∼15%). Improvements in muscle oxygenation with sildenafil were related to faster on-exercise Vo(2) kinetics, blunted oscillations in ventilation (n = 9), and greater exercise capacity (P < 0.05). Sildenafil intake enhanced intramuscular Qo(2mv)-to-Vo(2) matching with beneficial effects on Vo(2) kinetics and exercise tolerance in CHF. The lack of effect on CO suggests that improvement in blood flow to and within skeletal muscles underlies these effects.

Effects of inspiratory muscle training combined with aerobic exercise training on neurovascular control in chronic heart failure patients.

AIMS: We tested the hypothesis that the effects of combined inspiratory muscle training and aerobic exercise training (IMT + AET) on muscle sympathetic nerve activity (MSNA) and forearm blood flow in patients with heart failure with reduced ejection fraction are more pronounced than the effects of AET alone. METHODS AND RESULTS: Patients aged 30-70 years, New York Heart Association Functional Class II-III, and left ventricular ejection fraction ≤40% were randomly assigned to four groups: IMT (n = 11), AET (n = 12), IMT + AET (n = 9), and non-training (NT; n = 10). MSNA was recorded using microneurography. Forearm blood flow was measured by venous occlusion plethysmography and inspiratory muscle strength by maximal inspiratory pressure. IMT consisted of 30 min sessions, five times a week, for 4 months. Moderate AET consisted of 60 min sessions, three times a week for 4 months. AET (-10 ± 2 bursts/min, P = 0.03) and IMT + AET (-13 ± 4 bursts/min, P = 0.007) reduced MSNA. These responses in MSNA were not different between AET and IMT + AET groups. IMT (0.22 ± 0.08 mL/min/100 mL, P = 0.03), AET (0.27 ± 0.09 mL/min/100 mL, P = 0.01), and IMT + AET (0.35 ± 0.12 mL/min/100 mL, P = 0.008) increased forearm blood flow. No differences were found between groups. AET (3 ± 1 mL/kg/min, P = 0.006) and IMT + AET (4 ± 1 mL/kg/min, P = 0.001) increased peak oxygen consumption. These responses were similar between these groups. IMT (20 ± 3 cmH2 O, P = 0.005) and IMT + AET (18 ± 3 cmH2 O, P = 0.01) increased maximal inspiratory pressure. No significant changes were observed in the NT group. CONCLUSIONS: IMT + AET causes no additive effects on neurovascular control in patients with heart failure with reduced ejection fraction compared with AET alone. These findings may be, in part, because few patients had inspiratory muscle weakness.

Effects of aerobic and inspiratory training on skeletal muscle microRNA-1 and downstream-associated pathways in patients with heart failure.

BACKGROUND: The exercise intolerance in chronic heart failure with reduced ejection fraction (HFrEF) is mostly attributed to alterations in skeletal muscle. However, the mechanisms underlying the skeletal myopathy in patients with HFrEF are not completely understood. We hypothesized that (i) aerobic exercise training (AET) and inspiratory muscle training (IMT) would change skeletal muscle microRNA-1 expression and downstream-associated pathways in patients with HFrEF and (ii) AET and IMT would increase leg blood flow (LBF), functional capacity, and quality of life in these patients. METHODS: Patients age 35 to 70 years, left ventricular ejection fraction (LVEF) ≤40%, New York Heart Association functional classes II-III, were randomized into control, IMT, and AET groups. Skeletal muscle changes were examined by vastus lateralis biopsy. LBF was measured by venous occlusion plethysmography, functional capacity by cardiopulmonary exercise test, and quality of life by Minnesota Living with Heart Failure Questionnaire. All patients were evaluated at baseline and after 4 months. RESULTS: Thirty-three patients finished the study protocol: control (n = 10; LVEF = 25 ± 1%; six males), IMT (n = 11; LVEF = 31 ± 2%; three males), and AET (n = 12; LVEF = 26 ± 2%; seven males). AET, but not IMT, increased the expression of microRNA-1 (P = 0.02; percent changes = 53 ± 17%), decreased the expression of PTEN (P = 0.003; percent changes = -15 ± 0.03%), and tended to increase the p-AKTser473 /AKT ratio (P = 0.06). In addition, AET decreased HDAC4 expression (P = 0.03; percent changes = -40 ± 19%) and upregulated follistatin (P = 0.01; percent changes = 174 ± 58%), MEF2C (P = 0.05; percent changes = 34 ± 15%), and MyoD expression (P = 0.05; percent changes = 47 ± 18%). AET also increased muscle cross-sectional area (P = 0.01). AET and IMT increased LBF, functional capacity, and quality of life. Further analyses showed a significant correlation between percent changes in microRNA-1 and percent changes in follistatin mRNA (P = 0.001, rho = 0.58) and between percent changes in follistatin mRNA and percent changes in peak VO2 (P = 0.004, rho = 0.51). CONCLUSIONS: AET upregulates microRNA-1 levels and decreases the protein expression of PTEN, which reduces the inhibitory action on the PI3K-AKT pathway that regulates the skeletal muscle tropism. The increased levels of microRNA-1 also decreased HDAC4 and increased MEF2c, MyoD, and follistatin expression, improving skeletal muscle regeneration. These changes associated with the increase in muscle cross-sectional area and LBF contribute to the attenuation in skeletal myopathy, and the improvement in functional capacity and quality of life in patients with HFrEF. IMT caused no changes in microRNA-1 and in the downstream-associated pathway. The increased functional capacity provoked by IMT seems to be associated with amelioration in the respiratory function instead of changes in skeletal muscle. ClinicalTrials.gov (Identifier: NCT01747395).

Microvascular oxygen delivery-to-utilization mismatch at the onset of heavy-intensity exercise in optimally treated patients with CHF.

Impaired muscle blood flow at the onset of heavy-intensity exercise may transiently reduce microvascular O(2) pressure and decrease the rate of O(2) transfer from capillary to mitochondria in chronic heart failure (CHF). However, advances in the pharmacological treatment of CHF (e.g., angiotensin-converting enzyme inhibitors and third-generation beta-blockers) may have improved microvascular O(2) delivery to an extent that intramyocyte metabolic inertia might become the main locus of limitation of O(2) uptake (Vo(2)) kinetics. We assessed the rate of change of pulmonary Vo(2) (Vo(2)(p)), (estimated) fractional O(2) extraction in the vastus lateralis (approximately Delta[deoxy-Hb+Mb] by near-infrared spectroscopy), and cardiac output (Qt) during high-intensity exercise performed to the limit of tolerance (Tlim) in 10 optimally treated sedentary patients (ejection fraction = 29 + or - 8%) and 11 controls. Sluggish Vo(2)(p) and Qt kinetics in patients were significantly related to lower Tlim values (P < 0.05). The dynamics of Delta[deoxy-Hb+Mb], however, were faster in patients than controls [mean response time (MRT) = 15.9 + or - 2.0 s vs. 19.0 + or - 2.9 s; P < 0.05] with a subsequent response "overshoot" being found only in patients (7/10). Moreover, tauVo(2)/MRT-[deoxy-Hb+Mb] ratio was greater in patients (4.69 + or - 1.42 s vs. 2.25 + or - 0.77 s; P < 0.05) and related to Qt kinetics and Tlim (R = 0.89 and -0.78, respectively; P < 0.01). We conclude that despite the advances in the pharmacological treatment of CHF, disturbances in "central" and "peripheral" circulatory adjustments still play a prominent role in limiting Vo(2)(p) kinetics and tolerance to heavy-intensity exercise in nontrained patients.

Molecular profiling improves diagnoses of rejection and infection in transplanted organs.

The monitoring of transplanted hearts is currently based on histological evaluation of endomyocardial biopsies, a method that is fairly insensitive and that does not always accurately discriminate between rejection and infection in the heart. Accurate diagnosis of rejection and infection is absolutely crucial, however, as the respective treatments are completely different. Using microarrays, we analyzed gene expression in 76 cardiac biopsies from 40 heart recipients undergoing rejection, no rejection, or Trypanosoma cruzi infection. We found a set of genes whose expression patterns were typical of acute rejection, and another set of genes that discriminated between rejection and T cruzi infection. These sets revealed acute rejection episodes up to 2 weeks earlier, and trypanosome infection up to 2 months earlier than did histological evaluation. When applied to raw data from other institutions, the 2 sets of predictive genes were also able to accurately pinpoint acute rejection of lung and kidney transplants, as well as bacterial infections in kidneys. In addition to their usefulness as diagnostic tools, the data suggest that there are similarities in the biology of the processes involved in rejection of different grafts and also in the tissue responses to pathogens as diverse as bacteria and protozoa.

Prognostic value of real-time three-dimensional echocardiography compared to two-dimensional echocardiography in patients with systolic heart failure.

Heart failure (HF) is associated with morbidity and mortality. Real-time three-dimensional echocardiography (RT3DE) may offer additional prognostic data in patients with HF. The study aimed to evaluate the prognostic value of real-time three-dimensional echocardiography (RT3DE). This is a prospective study that included 89 patients with HF and left ventricular ejection fraction (LVEF) < 0.50 who were followed for 48 months. Left atrium and ventricular volumes and functions were evaluated by RT3DE. TDI and two-dimensional echocardiography parameters were also obtained. The endpoint was a composite of death, heart transplantation and hospitalization for acute decompensated HF. The mean age was 55 ± 11 years, and the LVEF was 0.32 ± 0.10. The composite endpoint occurred in 49 patients (18 deaths, 30 hospitalizations, one heart transplant). Patients with outcomes had greater left atrial volume (40 ± 16 vs. 32 ± 12 mL/m2; p < 0.01) and right ventricle diameter (41 ± 9 vs. 37 ± 8 mm, p = 0.01), worse total emptying fraction of the left atrium (36 ± 13% vs. 41 ± 11%; p = 0.03), LVEF (0.30 ± 0.09 vs. 0.34 ± 0.11; p = 0.02), right ventricle fractional area change (34.8 ± 12.1% vs. 39.2 ± 11.3%; p = 0.04), and greater E/e' ratio (19 ± 9 vs. 16 ± 8; p = 0.04) and systolic pulmonary artery pressure (SPAP) (50 ± 15 vs. 36 ± 11 mmHg; p < 0.01). In multivariate analysis, LVEF (OR 4.6; CI 95% 1.2-17.6; p < 0.01) and SPAP (OR 12.5; CI 95% 1.8-86.9; p < 0.01) were independent predictors of patient outcomes. LVEF and the SPAP were independent predictors of outcomes in patients with HF.

Myocardial dysfunction in mitochondrial diabetes treated with Coenzyme Q10.

Maternally-inherited diabetes and deafness (MIDD) has been related to an A to G transition in the mitochondrial tRNA Leu (UUR) gene at the base pair 3243. Although some previous articles have reported that this mutation may be a cause of cardiomyopathy in diabetes, the degree of cardiac involvement and a specific treatment has not been established. Here, we reported a case of a patient with MIDD who developed congestive heart failure and the therapeutic usefulness of Coenzyme Q10 (CoQ10). In our patient, after the introduction of Coenzyme Q10 150 mg/day, there was a gradual improvement on left ventricular function evaluated by echocardiography. The fractional shortening (FS) and ejection fraction (EF) increased from 26 to 34% and from 49 to 64%, respectively. No side effects were noted. Three months after CoQ10 discontinuation, the parameters of systolic function evaluated by echocardiography decreased, suggesting that CoQ10 had a beneficial effect. Identification of diabetes and cardiomyopathy due to mitochondrial gene mutation may have therapeutic implications and Coenzyme Q10 is a possible adjunctive treatment in such patients.

Effects of Zolpidem CR on Sleep and Nocturnal Ventilation in Patients with Heart Failure.

STUDY OBJECTIVE: This study aimed to evaluate the effects of zolpidem CR (controlled release) on sleep and nocturnal ventilation in patients with congestive heart failure, a population at risk for insomnia and poor sleep quality. METHODS: Fifteen patients with heart failure (ischemic cardiomyopathy) and ejection fraction ≤ 45% in NYHA functional class I or II were evaluated with full polysomnography in a placebo-controlled, double-blind, randomized trial. Patients underwent three tests: (1) baseline polysomnography and, after randomization, (2) a new test with zolpidem CR 12.5 mg or placebo, and after 1 week, (3) a new polysomnography, crossing the "medication" used. RESULTS: A 16% increase in total sleep time was found with the use of zolpidem CR and an increase in stage 3 NREM sleep (slow wave sleep). The apnea hypopnea index (AHI) did not change with zolpidem CR even after controlling for supine position; however, a slight but significant decrease was observed in lowest oxygen saturation compared with baseline and placebo conditions (83.60 ± 5.51; 84.43 ± 3.80; 80.71 ± 5.18, P = 0.002). CONCLUSION: Zolpidem CR improved sleep structure in patients with heart failure, did not change apnea hypopnea index, but slightly decreased lowest oxygen saturation.

Sleep-Disordered Breathing Exacerbates Muscle Vasoconstriction and Sympathetic Neural Activation in Patients with Systolic Heart Failure.

BACKGROUND: Sleep-disordered breathing (SDB) is common in patients with heart failure (HF), and hypoxia and hypercapnia episodes activate chemoreceptors stimulating autonomic reflex responses. We tested the hypothesis that muscle vasoconstriction and muscle sympathetic nerve activity (MSNA) in response to hypoxia and hypercapnia would be more pronounced in patients with HF and SDB than in patients with HF without SDB (NoSBD). METHODS AND RESULTS: Ninety consecutive patients with HF, New York Heart Association functional class II-III, and left ventricular ejection fraction ≤40% were screened for the study. Forty-one patients were enrolled: NoSDB (n=13, 46 [39-53] years) and SDB (n=28, 57 [54-61] years). SDB was characterized by apnea-hypopnea index ≥15 events per hour (polysomnography). Peripheral (10% O2 and 90% N2, with CO2 titrated) and central (7% CO2 and 93% O2) chemoreceptors were stimulated for 3 minutes. Forearm and calf blood flow were evaluated by venous occlusion plethysmography, MSNA by microneurography, and blood pressure by beat-to-beat noninvasive technique. Baseline forearm blood flow, forearm vascular conductance, calf blood flow, and calf vascular conductance were similar between groups. MSNA was higher in the SDB group. During hypoxia, the vascular responses (forearm blood flow, forearm vascular conductance, calf blood flow, and calf vascular conductance) were significantly lower in the SDB group compared with the NoSDB group (P<0.01 to all comparisons). Similarly, during hypercapnia, the vascular responses (forearm blood flow, forearm vascular conductance, calf blood flow, and calf vascular conductance) were significantly lower in the SDB group compared with the NoSDB group (P<0.001 to all comparisons). MSNA were higher in response to hypoxia (P=0.024) and tended to be higher to hypercapnia (P=0.066) in the SDB group. CONCLUSIONS: Patients with HF and SDB have more severe muscle vasoconstriction during hypoxia and hypercapnia than HF patients without SDB, which seems to be associated with endothelial dysfunction and, in part, increased MSNA response.

A Cycle Ergometer Exercise Program Improves Exercise Capacity and Inspiratory Muscle Function in Hospitalized Patients Awaiting Heart Transplantation: a Pilot Study.

Objective: The purpose of this study was to evaluate the effect of a cycle ergometer exercise program on exercise capacity and inspiratory muscle function in hospitalized patients with heart failure awaiting heart transplantation with intravenous inotropic support. Methods: Patients awaiting heart transplantation were randomized and allocated prospectively into two groups: 1) Control Group (n=11) - conventional protocol; and 2) Intervention Group (n=7) - stationary cycle ergometer exercise training. Functional capacity was measured by the six-minute walk test and inspiratory muscle strength assessed by manovacuometry before and after the exercise protocols. Results: Both groups demonstrated an increase in six-minute walk test distance after the experimental procedure compared to baseline; however, only the intervention group had a significant increase (P =0.08 and P =0.001 for the control and intervention groups, respectively). Intergroup comparison revealed a greater increase in the intervention group compared to the control (P <0.001). Regarding the inspiratory muscle strength evaluation, the intragroup analysis demonstrated increased strength after the protocols compared to baseline for both groups; statistical significance was only demonstrated for the intervention group, though (P =0.22 and P <0.01, respectively). Intergroup comparison showed a significant increase in the intervention group compared to the control (P <0.01). Conclusion: Stationary cycle ergometer exercise training shows positive results on exercise capacity and inspiratory muscle strength in patients with heart failure awaiting cardiac transplantation while on intravenous inotropic support.

Pre- and post-transplant anti-myosin and anti-heat shock protein antibodies and cardiac transplant outcome.

BACKGROUND: The purpose this study was to investigate the relationship of anti-myosin and anti-heat shock protein immunoglobulin G (IgG) serum antibodies to the original heart disease of cardiac transplant recipients, and also to rejection and patient survival after cardiac transplantation. METHODS: Anti-myosin and anti-heat shock protein (anti-hsp) IgG antibodies were evaluated in pre-transplant sera from 41 adult cardiac allograft recipients and in sequential post-transplant serum samples from 11 recipients, collected at the time of routine endomyocardial biopsies during the first 6 months after transplantation. In addition, the levels of these antibodies were determined from the sera of 28 healthy blood donors. RESULTS: Higher anti-myosin antibody levels were observed in pre-transplant sera than in sera from normal controls. Moreover, patients with chronic Chagas heart disease showed higher anti-myosin levels than patients with ischemic heart disease, and also higher levels, although not statistically significant, than patients with dilated cardiomyopathy. Higher anti-hsp levels were also observed in patients compared with healthy controls, but no significant differences were detected among the different types of heart diseases. Higher pre-transplant anti-myosin, but not anti-hsp, levels were associated with lower 2-year post-transplant survival. In the post-transplant period, higher anti-myosin IgG levels were detected in sera collected during acute rejection than in sera collected during the rejection-free period, whereas anti-hsp IgG levels showed no difference between these periods. CONCLUSIONS: The present findings are of interest for post-transplant management and, in addition, suggest a pathogenic role for anti-myosin antibodies in cardiac transplant rejection, as has been proposed in experimental models of cardiac transplantation.

Vasoplegic syndrome after off-pump coronary artery bypass surgery.

OBJECTIVE: The vasoplegic syndrome (VS) has been implicated in life-threatening complications after open heart surgery, where the whole-body inflammatory reaction is attributed to the cardiopulmonary bypass (CPB). Off-pump coronary artery bypass grafting (OPCAB) has been recently achieving growing enthusiasm mainly due avoiding the side effects of CPB. However herein the occurrence of VS in OPCAB is reported. METHODS: The vasoplegic syndrome usual findings occurring in the early postoperative period include severe hypotension, tachycardia, normal or elevated cardiac output and low systemic vascular resistance. Four patients underwent to OPCAB presented all the signs of VS intraoperatively or within the first 6 postoperative h. RESULTS: The patients needed aggressive vasoactive drug support for hemodynamic stabilization and all of them developed complications. These patients also had tendency to require administration of blood and blood derivatives due to diffuse and oozing type bleeding. Mean intensive care unit stay of surviving patients was 70 h and mean period of postoperative hospitalization was 9 days. Tumor necrosis factor-alpha blood levels in one patient were elevated postoperatively though no signs of infection were observed. One patient died. CONCLUSIONS: Although vasoplegic syndrome can complicate OPCAB surgery, the rationale for avoiding CPB remains valid considering the benefits provided by OPCAB.

Neurologic complications after heart transplantation.

OBJECTIVE: Neurologic complications are known as important cause of morbidity and mortality in orthotopic heart transplantation. Our aim was to identify the frequency and outcome of neurologic complications after heart transplantation in a prospective observational study. METHOD: From September 93 to September 99, as part of our routine heart transplantation protocol all patients with end-stage cardiac failure were evaluated by the same neurologist before and at the time of any neurologic event (symptom or complaint) after transplantation. RESULTS: Out of 120 candidates evaluated, 62 were successfully transplanted (53 male; median age 45.5 years, median follow-up 26.8 months). Fifteen patients (24%) had ischemic, 22 (35%) idiopathic, 24 (39%) Chagas' disease and 1 (2%) had congenital cardiomyopathy. Neurologic complications occurred in 19 patients (31%): tremor, severe headache, transient encephalopathy and seizures related to drug toxicity or metabolic changes in 13; peripheral neuropathy in 4; and spinal cord compression in two (metastatic prostate cancer and epidural abscess). No symptomatic postoperative stroke was observed. CONCLUSIONS: Although frequent, neurologic complications were seldom related to persistent neurologic disability or death. Most of the complications resulted from immunosuppression, however, CNS infection was rare. The absence of symptomatic stroke in our series may be related to the lower frequency of ischemic cardiomyopathy.

Hospitalization and mortality rates for heart failure in public hospitals in São Paulo.

BACKGROUND: Advances in the treatment of heart failure (HF) have resulted in reduced mortality and hospitalization rates. On the other hand, when hospitalized, patients are at high risk of death. OBJECTIVE: As there are few studies in this group of patients in Brazil, we analyzed the numbers of hospitalization and deaths due to HF in the Brazilian Public Health System (SUS) in the city of São Paulo. METHODS: Historical prospective study carried out between 1992 and 2010. The data were obtained from DATASUS. We used Chi-square and t tests for comparison between the periods 1992-1993 and 2008-2009 and logistic regression models when appropriate. The level of significance was set at 5%. RESULTS: There was a 32% decrease in the number of hospitalizations for HF between 1992-1993 and 2008-2009 (p = 0.002). The in-hospital mortality rate for HF was 15%, with a 15% increase in the period (p = 0.004). Between 1992 and 1993, the mean time of hospitalization for HF was 8.8 days. Between 2008 and 2009, it was 11.3 days (p = 0.001). August was the month with the highest incidence of hospitalizations for HF, 20% higher than in February, the month with the lowest incidence (p = 0.041). CONCLUSION: This study showed changes in trends of hospitalization for HF and mortality over the last two decades. We emphasize important implications: 1: 32% decrease in the number of hospitalizations for HF in SUS hospitals in São Paulo; 2: 25% increase in hospitalization time, and 3: seasonal pattern of hospitalization for HF, with a peak in the third quarter.

Left atrial dysfunction in chagas cardiomyopathy is more severe than in idiopathic dilated cardiomyopathy: a study with real-time three-dimensional echocardiography.

BACKGROUND: Although there is anatomopathologic evidence of atrial involvement in Chagas cardiomyopathy (CCM), the impact in left atrial (LA) function is unknown. The aim of this study was to evaluate LA function in patients with CCM with real-time three-dimensional echocardiography (RT3DE) and to compare it with patients with idiopathic dilated cardiomyopathy (DCM). METHODS: A total of 30 patients with CCM, 30 patients with DCM, and 20 normal subjects used as the control group were studied. With the use of RT3DE, we measured LA maximum (maxLAV), minimum, and pre-atrial contraction volumes and calculated total and active LA emptying fractions. RESULTS: Left ventricular ejection fraction and mitral regurgitation were similar in both groups. MaxLAV/m(2) was larger in the CCM group than in the DCM group (76.9 ± 21.9 mL vs. 59.1 ± 26.0 mL; P < .01), and both were significantly larger than in the control group (P < .01). Total LA emptying fraction was lower in the CCM group than in the DCM group (0.30 ± 0.10 vs. 0.40 ± 0.12; P < .01), and both were lower than in the control group (P = .01). Active LA emptying fraction was also lower in the CCM group than in the DCM group (0.22 ± 0.09 vs. 0.28 ± 0.11; P < .01), and both were lower than in the control group (P = .01). The E/e' ratio was higher in the CCM group than in the DCM group (21 ± 10 vs. 15 ± 6; P < .01), and both were greater than in the control group (P < .01). In a multiple regression model, the E/e' ratio was the only independent predictor of a worsening active LA emptying fraction. CONCLUSION: LA function is more compromised in patients with CCM than in patients with DCM. This finding indicates a more diffuse and severe myocardial impairment in Chagas disease that is probably related to increased left ventricular filling pressures and atrial myopathy.

A cycle ergometer exercise program improves exercise capacity and inspiratory muscle function in hospitalized patients awaiting heart transplantation: a pilot study

Abstract Objective: The purpose of this study was to evaluate the effect of a cycle ergometer exercise program on exercise capacity and inspiratory muscle function in hospitalized patients with heart failure awaiting heart transplantation with intravenous inotropic support. Methods: Patients awaiting heart transplantation were randomized and allocated prospectively into two groups: 1) Control Group (n=11) - conventional protocol; and 2) Intervention Group (n=7) - stationary cycle ergometer exercise training. Functional capacity was measured by the six-minute walk test and inspiratory muscle strength assessed by manovacuometry before and after the exercise protocols. Results: Both groups demonstrated an increase in six-minute walk test distance after the experimental procedure compared to baseline; however, only the intervention group had a significant increase (P =0.08 and P =0.001 for the control and intervention groups, respectively). Intergroup comparison revealed a greater increase in the intervention group compared to the control (P <0.001). Regarding the inspiratory muscle strength evaluation, the intragroup analysis demonstrated increased strength after the protocols compared to baseline for both groups; statistical significance was only demonstrated for the intervention group, though (P =0.22 and P <0.01, respectively). Intergroup comparison showed a significant increase in the intervention group compared to the control (P <0.01). Conclusion: Stationary cycle ergometer exercise training shows positive results on exercise capacity and inspiratory muscle strength in patients with heart failure awaiting cardiac transplantation while on intravenous inotropic support.