Augmented Cardiopulmonary Baroreflex Sensitivity in Intradialytic Hypertension.

IntroductionEnd-stage renal disease (ESRD) patients with a paradoxical increase in blood pressure (BP) during hemodialysis (HD), termed intradialytic hypertension (ID-HTN), are at significantly increased risk for mortality and adverse cardiovascular events. ID-HTN affects up to 15% of all HD patients, and the pathophysiologic mechanisms remain unknown. We hypothesized that ESRD patients prone to ID-HTN have heightened volume-sensitive cardiopulmonary baroreflex sensitivity (BRS) that leads to exaggerated increases in sympathetic nervous system (SNS) activation during HD.MethodsWe studied ESRD patients on maintenance HD with ID-HTN (n = 10) and without ID-HTN (controls, n = 12) on an interdialytic day, 24 to 30 hours after their last HD session. We measured continuous muscle sympathetic nerve activity (MSNA), beat-to-beat arterial BP, and electrocardiography (ECG) at baseline, and during graded lower body negative pressure (LBNP). Low-dose LBNP isolates cardiopulmonary BRS, whereas higher doses allow assessment of physiologic responses to orthostatic stress.ResultsThe ID-HTN patients had significantly higher pre- and post-HD BP, and greater interdialytic fluid weight gain compared to controls. There was a significantly greater increase in MSNA burst incidence (P = 0.044) during graded LBNP in the ID-HTN group, suggesting heightened cardiopulmonary BRS. The ID-HTN group also had a trend toward increased diastolic BP response during LBNP, and had significantly greater increases in BP during the cold pressor test.ConclusionPatients with ID-HTN have augmented cardiopulmonary BRS that may contribute to increased SNS activation and BP response during HD

Testosterone deficiency increases hospital readmission and mortality rates in male patients with heart failure.

BackgroundTestosterone deficiency in patients with heart failure (HF) is associated with decreased exercise capacity and mortality; however, its impact on hospital readmission rate is uncertain. Furthermore, the relationship between testosterone deficiency and sympathetic activation is unknown.ObjectiveWe investigated the role of testosterone level on hospital readmission and mortality rates as well as sympathetic nerve activity in patients with HF.MethodsTotal testosterone (TT) and free testosterone (FT) were measured in 110 hospitalized male patients with a left ventricular ejection fraction < 45% and New York Heart Association classification IV. The patients were placed into low testosterone (LT; n = 66) and normal testosterone (NT; n = 44) groups. Hypogonadism was defined as TT < 300 ng/dL and FT < 131 pmol/L. Muscle sympathetic nerve activity (MSNA) was recorded by microneurography in a subpopulation of 27 patients.ResultsLength of hospital stay was longer in the LT group compared to in the NT group (37 ± 4 vs. 25 ± 4 days; p = 0.008). Similarly, the cumulative hazard of readmission within 1 year was greater in the LT group compared to in the NT group (44% vs. 22%, p = 0.001). In the single-predictor analysis, TT (hazard ratio [HR], 2.77; 95% confidence interval [CI], 1.58-4.85; p = 0.02) predicted hospital readmission within 90 days. In addition, TT (HR, 4.65; 95% CI, 2.67-8.10; p = 0.009) and readmission within 90 days (HR, 3.27; 95% CI, 1.23-8.69; p = 0.02) predicted increased mortality. Neurohumoral activation, as estimated by MSNA, was significantly higher in the LT group compared to in the NT group (65 ± 3 vs. 51 ± 4 bursts/100 heart beats; p < 0.001).ConclusionThese results support the concept that LT is an independent risk factor for hospital readmission within 90 days and increased mortality in patients with HF. Furthermore, increased MSNA was observed in patients with LT

948-46 Preserved Cardiac Baroreflex Control of Renal Cortical Blood Flow in Advanced Heart Failure Patients: A Positron Emission Tomography Study

Cardiac baroreflex (CBR) control of forearm blood flow (FBF) is blunted or reversed in humans with heart failure (HF). but little is known about CBR control of renal cortical blood flow (RCBF) in HF due to technical limitations. Positron emission tomography (PET) 0–15 water is a new, precise method to measure RCBF quantitatively. We compared CBR control of RCBF and FBF (venous plethysmography) in 8 patients with HF (mean age, 47±3 y, ejection fraction 0.25±0.02) and 10 normal humans (mean age 35±5 y) during CBR unloading with phlebotomy (450ml). In 5 normals, cold pressor test was used as a strong, non-baroreflex mediated stimulus to vasoconstriction.ResultsPhlebotomy decreased central venous pressure (p <0.001), but did not change mean arterial pressure or heart rate in HF patients or controls. The major findings of the study are: 1) At rest, RCBF is markedly diminished in HF vs normals (2.4±0.1 vs 4.3±0.2ml/min/g, p < 0.001). 2) In normal humans during phlebotomy, FBF decreased substantially (basal vs phlebotomy: 3.3±0.4 vs 2.6±0.3 ml/min/100 ml, p=0.021, and RCBF decreased slightly, but significantly (basal vs phlebotomy: 4.3±0.2 vs 4.0±0.3 ml/min/g, p=0.01). 3) The small magnitude of reflex renal vasoconstriction is not explained by the inability of the renal circulation to vasoconstrict since the cold pressor stimulus induced substantial decreases in RCBF in normals (basal vs cold pressor: 4.4±0.1 vs 3.7±0.1 ml/min/g, p=0.003). 4) In humans with heart failure during phlebotomy, FBF did not change (basal vs phlebotomy: 2.6±0.3 vs 2.7±0.2 ml/min/100 ml, p=NS), but RCBF decreased slightly but significantly (basal vs phlebotomy: 2.4±0.1 vs 2.1±0.1 ml/min/g, p=0.01). Thus, in patients with heart failure, there is an abnormality in cardiopulmonary baroreflex control of the forearm circulation, but not the renal circulationConclusionThis study 1) shows the power of PET to study physiologic and pathophysiologic reflex control of the renal circulation in humans, and 2) describes the novel finding of selective dysfunction of cardiac baroreflex control of the forearm circulation, but its preservation of the renal circulation, in patients with heart failur

981-46 Impact of a Comprehensive Management Program on the Hospitalization Rate for Patients with Advanced Heart Failure

Patients with advanced heart failure have a course that is often characterized by frequent hospitalizations and progressive deterioration. These patients are commonly referred to specialized centers for consideration of heart transplantation (Tx). To assess the impact of the changes in therapy made in conjunction with heart transplantation evaluation on patient outcomes, we assessed the hospitalization rate and patient's functional status in the 6 months prior to referral compared to the 6 months after referral. Since 1/91, 214 patients were evaluated, accepted for Tx, and discharged having undergone adjustments in medical therapy and a comprehensive patient education program. At time of referral patients had mean LVEF 0.21, NYHA class 3.3, VO2 max 11.0ml/kg, and had undergone a total of 429 hospitalizations in the previous 6 months. During evaluation patients had their ACE inhibitor dose increased by a mean 91.5mg/day of captopril or the equivalent, were diuresed a mean 4.2 liters, were placed on a flexible regimen of loop diuretics, and were counseled on dietary management and home based progressive aerobic exercise. After 6 months of follow-up there were only 63 hospitalizations required (mean hospitalization rate per patient over the 6 months pre-evaluation 2.00±1.45 vs post-evaluation 0.29±0.53 p<0.00001). Patient's NYHA class improved to 2.4 (p<0.0001) and VO2 max increased to 15.2 (p<0.001). Excluding the 12 elective status Tx, 14 urgent status Tx, and 9 deaths within 6 months yielded similar results (344 pre vs 34 post-evaluation hospitalizations). 64 patients (30%) improved their functional status to the point that transplantation was deferred in favor of sustained medical therapy.Referral to a heart failure specialty program is associated with a dramatic occurred between day 10±1 and 3 month. 4 patients died after hospital discharge (no death directly related to thromboembolic disease). Thus no higher risk of PE can be seen in patients with free floating prox-DVT and anticoagulant therapy should be efficient to prevent recurrent PE in such patient

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 (V) over dot O-2 <= 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.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundacao ZerbiniCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)National Heart, Lung, and Blood InstituteUniv São Paulo, Sch Med, Heart Inst InCor, São Paulo, BrazilUniv São Paulo, Sch Phys Educ & Sport, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, Div Cardiol, São Paulo, BrazilUniv Calif Los Angeles, David Geffen Sch Med, Dept Med Cardiol & Physiol, Los Angeles, CA 90095 USAUniversidade Federal de São Paulo, Dept Med, Div Cardiol, São Paulo, BrazilFAPESP: 2010/50048-1FAPESP: 140643/2009-5FAPESP: 2013/07651-7CNPq: 142366/2009-9CNPq: 301867/2010-0CNPq: 308068/2011-4FAPESP: 2013/15651-7National Heart, Lung, and Blood Institute: RO1-HL084525Web of Scienc

Improving survival for patients with advanced heart failure: A study of 737 consecutive patients

Objectives.This study sought to determine whether survival and risk of sudden death have improved for patients with advanced heart failure referred for consideration for heart transplantation as advances in medical therapy were systematically implemented over an 8-year period.Background.Recent survival trials in patients with mild to moderate heart failure and patients after a myocardial infarction have shown that angiotensin-converting enzyme inhibitors are beneficial, type I antiarrhythmic drugs can be detrimental, and amiodarone may be beneficial in some groups. The impact of advances in therapy may be enhanced or blunted when applied to severe heart failure.Methods.One-year mortality and sudden death were determined in relation to time, baseline variables and therapeutics for 737 consecutive patients referred for heart transplantation and discharged home on medical therapy from 1986 to 1988, 1989 to 1990 and 1991 to 1993. Medical care was directed by a single team of physicians with policies established by consensus. From 1986 to 1990, the hydralazine/isosorbide dinitrate combination or angiotensin-converting enzyme inhibitors were the initial vasodilators, and class I antiarrhythmic drugs were allowed. After 1990, captopril was the initial vasodilator, given to 86% of patients compared with 46% of patients before 1989. After mid-1989, class I agents were routinely withdrawn, and amiodarone was used for frequent ventricular ectopic beats or atrial fibrillation (53% of patients after 1990 vs. 10% before 1989).Results.The total 1-year mortality rate decreased from 33% before 1989 to 16% after 1990 (p = 0.0001), and sudden death decreased from 20% to 8% (p = 0.0006). Adjusted for clinical and hemodynamic variables in multivariate proportional hazards models, total mortality and sudden death were lower after 1990.Conclusions.The large reduction in mortality, particularly in sudden death, from advanced heart failure since 1990 may reflect an enhanced impact of therapeutic advances shown in large randomized trials when they are incorporated into a comprehensive approach in this population. This improved survival supports the growing practice of maintaining potential heart transplant candidates on optimal medical therapy until clinical decompensation mandates transplantation

Cardiovascular impact of electronic-cigarette use.

The majority of premature deaths related to tobacco cigarettes (TCs) are attributable to cardiovascular disease, so it is fitting and timely to review the overall cardiovascular impact of electronic cigarettes (ECs), which have recently exploded onto the tobacco product market. Longitudinal studies of EC users are necessary, but not yet available, to answer the question whether cardiovascular disease is lower in chronic EC users compared to TC smokers, so we must rely on biomarker studies. Several biomarkers that portend increased cardiovascular risk, including markers of increased sympathetic nerve activity, oxidative stress and inflammation, vascular dysfunction, and thrombosis, have been reported to be abnormal after EC use, although often not to the degree found in TC smokers. We conclude that if all FDA-certified strategies for TC smoking cessation have been tried without success, then ECs may be a reasonable strategy for TC smoking cessation, but the message to non-TC smokers must be clear and unwavering: non TC-smokers should not use ECs - they are not harmless

Cardiovascular impact of electronic-cigarette use.

The majority of premature deaths related to tobacco cigarettes (TCs) are attributable to cardiovascular disease, so it is fitting and timely to review the overall cardiovascular impact of electronic cigarettes (ECs), which have recently exploded onto the tobacco product market. Longitudinal studies of EC users are necessary, but not yet available, to answer the question whether cardiovascular disease is lower in chronic EC users compared to TC smokers, so we must rely on biomarker studies. Several biomarkers that portend increased cardiovascular risk, including markers of increased sympathetic nerve activity, oxidative stress and inflammation, vascular dysfunction, and thrombosis, have been reported to be abnormal after EC use, although often not to the degree found in TC smokers. We conclude that if all FDA-certified strategies for TC smoking cessation have been tried without success, then ECs may be a reasonable strategy for TC smoking cessation, but the message to non-TC smokers must be clear and unwavering: non TC-smokers should not use ECs - they are not harmless