Exercise-induced biphasic increase in circulating NT-proBNP levels in patients with chronic heart failure

BACKGROUND: Exercise increases natriuretic peptide levels in chronic heart failure (CHF) patients, but the effect is considered minor. We assessed acute and short-term release (<24 h) of NT-proBNP in CHF patients after a maximal cardiopulmonary exercise test (CPET) and 2 different submaximal training sessions. METHODS AND RESULTS: 102 CHF patients either performed CPET (Group 1), a 1 h endurance (Group 2) or a combined endurance-resistance training session (Group 3). NT-proBNP concentration was determined before, at exercise cessation and after 18-22 h (Protocol A). In 20 patients, samples were obtained before, at exercise cessation, after 15, 30, 45, 60, 90 min, 2, 3, 4, 5, 6, 12, 22 h (Protocol B). Protocol A: At peak exercise, a 15%, 11% and 17% relative increase (p<0.001 vs baseline, all 3 groups) was seen, with a return to baseline after 18-22 h. The increase correlated with indicators of more advanced heart failure. Protocol B: A biphasic pattern was derived with a first peak within 1 h of exercise termination and a second peak (39%, 31% and 33% higher than baseline; p<0.05, all 3 groups) after 4-12 h. CONCLUSIONS: The observed biphasic release of B-type natriuretic peptides supports standardization of sampling, taking recent exercise into account.     

Usefulness of arterial blood gas estimations during exercise in patients with chronic heart failure.

BACKGROUND--Coexisting cardiorespiratory disease may contribute in individual cases to the increased ventilatory response to exercise in patients with chronic heart failure. OBJECTIVE--To characterise further the arterial blood gas response to exercise and to explore the possible uses of blood gas sampling in clinical practice in patients with chronic heart failure. METHODS--37 patients with a primary diagnosis of chronic heart failure (age (range) 59 (45-80); left ventricular ejection fraction 24.5% (4%-44%)) underwent exercise testing with arterial blood gas analysis during exercise. RESULTS--In 34 patients there was a small fall in arterial carbon dioxide tension from a mean (SEM) of 4.9 (0.1) kPa at rest to 4.6 (0.1) kPa at peak exercise (p < 0.001). There was no significant change in arterial oxygen tension. During the recovery period arterial oxygen tension rose from 13.3 (0.3) kPa at peak exercise to 14.8 (0.3) kPa three minutes into recovery (p < 0.001). Arterial carbon dioxide tension was unchanged. In the remaining three patients there was considerable arterial hypoxaemia on exercise, from 10.4 kPa at rest to 7.7 kPa at peak exercise. All of these patients had an alternative diagnosis (patent foramen ovale with right to left shunt during exercise, pulmonary embolic disease, and clinically unsuspected obstructive airways disease). CONCLUSION--Patients with a presumptive diagnosis of chronic heart failure should undergo exercise testing with arterial blood gas analysis. Arterial hypoxaemia on exercise is rare in stable chronic heart failure. If hypoxia on exercise is detected, an alternative diagnosis should be sought.     

Effects of omapatrilat on systemic arterial function in patients with chronic heart failure

The mechanisms of action of omapatrilat, an agent that inhibits both neutral endopeptidase 24.11 and angiotensin-converting enzyme, on arterial function in patients with heart failure have not been previously reported. Forty-eight patients in New York Heart Association functional class II to III, left ventricular ejection fraction < or = 40%, and in sinus rhythm were randomized to a dose-ranging (2.5, 5, 10, 20, or 40 mg) study of omapatrilat for 12 weeks. Measurements were obtained at baseline and 12 weeks. Decreases in systolic (25.0 +/- 4.5 vs 2.8 +/- 5.0 mm Hg, p < 0.05) and mean arterial (13.9 +/- 3.0 vs 0.3 +/- 3.3 mm Hg, p < 0.05) pressure were seen after 12 weeks of therapy with higher doses. Ventricular-arterial coupling was improved with a dose-related decrease in augmentation index (-13.8 +/- 1.7% vs +6.1 +/- 2.1%, p < 0.01). There was no change in resting forearm blood flow between groups; however, maximum forearm vasodilator response during reactive hyperemia increased in the high-dose groups compared with the control group (+266 +/- 43% vs - 14 +/- 92%, p < 0.05). Omapatrilat induced an increase in postdose plasma atrial natriuretic peptide levels (30 +/- 11 vs -2 +/- 7 pmol/L, p < 0.01) in high-dose groups consistent with endopeptidase 24.11 inhibition. Omapatrilat shows beneficial changes in ventricular-vascular coupling and arterial function in heart failure.     

Mechanical alternans in patients with chronic heart failure.

BACKGROUND: Clinical implications of mechanical alternans in patients with chronic heart failure have remained uncertain. In this study, prevalence, characteristics, and prognostic implications of mechanical alternans were investigated. METHODS AND RESULTS: Consecutive 51 patients with dilated cardiomyopathy underwent diagnostic cardiac catheterization using a micromanometer-tipped catheter. Under basal conditions, 7 of 35 patients with sinus rhythm showed mechanical alternans. Physiologic tachycardia (110 bpm) induced mechanical alternans in another 15 patients with sinus rhythm and in another 10 of 16 patients with atrial fibrillation. Low doses of dobutamine also induced mechanical alternans in another 8 patients, but a high dose of dobutamine eliminated mechanical alternans. Consequently, 40 patients (78%) showed mechanical alternans. Mechanical alternans was always accompanied by alternating changes of positive dP/dt, a parameter of contractility during isovolumetric contraction time, but negative dP/dt was occasionally constant. Concordant mechanical alternans between both ventricles was more prevalent than discordant alternans. The left ventricular end-diastolic volume indices and end-systolic volume indices of patients with mechanical alternans were larger than those of patients without. The left ventricular ejection fraction of patients with alternans was significantly lower than that of patients without. CONCLUSIONS: Mechanical alternans was highly prevalent in patients with chronic heart failure. The origin of mechanical alternans seems to exist before or at the isovolumetric contraction time.     

Chemoreflexsensitivity in chronic heart failure patients.

AIMS: Patients with heart failure are characterised by a disturbed sympathovagal balance, as could be shown by analyses of heart rate variability and baroreflexsensitivity. Furthermore, the modulation of ventilation is disturbed in those patients with an increased ventilation volume following the inhalation of hypoxic gas. This study should evaluate, whether heart failure patients have a decreased hyperoxic chemoreflexsensitivity associated with an increased rate of ventricular arrhythmias. METHODS AND RESULTS: Into this study, 49 consecutive patients were enrolled. Of these, 23 suffered from heart failure; the remaining had no evidence of heart failure and a normal left ventricular ejection fraction. All patients were investigated by analysing the reduction of heart rate following inhalation of pure oxygen. The difference of RR-interval divided by the difference of the venous oxygen partial pressure both before and after oxygen inhalation resulted in the chemoreflexsensitivity. Patients with heart failure showed a significantly decreased chemoreflexsensitivity compared to those without (2.62+/-1.85 vs. 5.80+/-6.37 ms/mmHg, P<0.05). Of patients with heart failure, 69.6% had a decreased chemoreflexsensitivity below 3 ms/mmHg, in contrast to only 38.5% of the control group. Patients with decreased chemoreflexsensitivity showed significantly more non-sustained ventricular tachycardias (46 vs. 4%, P<0.05) during Holter ECG. CONCLUSION: Patients with heart failure show a significantly decreased hyperoxic chemoreflexsensitivity. A decreased chemoreflexsensitivity is associated with an increased rate of non-sustained ventricular tachycardias. This may be related to an increased sympathetic tone in these patients. The chemoreflexsensitivity may be important in arrhythmic risk stratification of patients with heart failure.     

Trepopnea in patients with chronic heart failure

This article will review the recumbent positions of patients with chronic congestive heart failure. The time for the right lateral decubitus position was two-fold longer than that for the supine and left lateral decubitus positions. Sympathetic nervous modulation was most attenuated and parasympathetic tone was most augmented in the right lateral decubitus position. The underlying mechanisms why heart failure patients prefer this position will be discussed. In conclusion, the right lateral decubitus position preferred by patients with chronic congestive heart failure may be a self-protecting mechanism to augment cardiac output and to attenuate the imbalance of cardiac autonomic nervous activity.     

Altered intestinal function in patients with chronic heart failure.

OBJECTIVES: We evaluated morphology and function of the gut in patients with chronic heart failure (CHF). BACKGROUND: Intestinal translocation of bacterial endotoxin may contribute to the inflammatory state observed in patients with CHF. The morphology and function of the gut may be abnormal. METHODS: We studied 22 patients with CHF (age 67 +/- 2 years, left ventricular ejection fraction [LVEF] 31 +/- 1%, New York Heart Association functional class 2.3 +/- 0.1, peak VO2 15.0 +/- 1.0 ml/kg/min) and 22 control subjects (62 +/- 1 years, LVEF 68 +/- 2%, peak VO2 24.7 +/- 1.3 ml/kg/min). Bowel wall thickness was assessed by transcutaneous sonography, small intestinal permeability by the lactulose-mannitol test, passive carrier-mediated transport by D-xylose test, large intestinal permeability by sucralose test (5- and 26-h urine collection, high-performance liquid chromatography), and mucosal bacterial biofilm by fluorescence in situ hybridization in biopsies taken during sigmoidoscopy. RESULTS: Chronic heart failure patients, compared with control patients, showed increased bowel wall thickness in the terminal ileum (1.48 +/- 0.16 mm vs. 1.04 +/- 0.08 mm), ascending colon (2.32 +/- 0.18 mm vs. 1.31 +/- 0.14 mm), transverse colon (2.19 +/- 0.20 vs. 1.27 +/- 0.08 mm), descending colon (2.59 +/- 0.18 mm vs. 1.43 +/- 0.13 mm), and sigmoid (2.97 +/- 0.27 mm vs. 1.64 +/- 0.14 mm) (all p < 0.01). Chronic heart failure patients had a 35% increase of small intestinal permeability (lactulose/mannitol ratio: 0.023 +/- 0.001 vs. 0.017 +/- 0.001, p = 0.006), a 210% increase of large intestinal permeability (sucralose excretion: 0.62 +/- 0.17% vs. 0.20 +/- 0.06%, p = 0.03), and a 29% decrease of D-xylose absorption, indicating bowel ischemia (26.7 +/- 3.0% vs. 37.4 +/- 1.4%, p = 0.003). Higher concentrations of adherent bacteria were found within mucus of CHF patients compared with control subjects (p = 0.007). CONCLUSIONS: Chronic heart failure is a multisystem disorder in which intestinal morphology, permeability, and absorption are modified. Increased intestinal permeability and an augmented bacterial biofilm may contribute to the origin of both chronic inflammation and malnutrition.     

Inspiratory muscle endurance in patients with chronic heart failure.

OBJECTIVE: To assess the significance of changes in respiratory muscle endurance in relation to respiratory and limb muscle strength in patients with mild to moderate chronic heart failure using a threshold loading technique. SUBJECTS: 20 patients with chronic heart failure (17 male) aged 63.8 (SD 7.4) years and 10 healthy men aged 63.1 (5.6) years. Heart failure severity was New York Heart Association (NYHA) grade II (n = 11) and NYHA grade III/IV (n = 9). METHODS: Respiratory muscle strength was measured from mouth pressures during maximum inspiratory effort (MIP) at functional residual capacity (FRC) and limb muscle strength was measured using a hand grip dynamometer. Inspiratory muscle endurance was measured using a threshold loading technique. The total endurance duration, the maximum threshold pressure achieved (P-Max), and the inspiratory load (% ratio of P-Max/MIP) were recorded in all subjects. RESULTS: Inspiratory muscles were weaker in patients with heart failure than in the controls [MIP 53.6 (16.5) v 70.9 (20.2) cm H2O, P < 0.05]. Hand grip strength was similar in both subject groups [31.6 (SD) v 36.1 (15.9) dynes]. Total endurance duration was significantly reduced in the patient group [494 (223) v 996 (267) s, P < 0.01], as was the maximal threshold pressure achieved [P-Max 18.5 (6.4) v 30.7 (6.6) cm H2O, P < 0.01]. When expressed as a percentage of MIP, P-Max was also lower in the patients [35.2 (11.8) v 44.8 (11.4)%, P < 0.05]. There was no significant correlation between any measure of endurance and limb muscle strength. CONCLUSIONS: Respiratory muscle endurance is reduced in patients with chronic heart failure. These changes probably reflect a generalised skeletal myopathy and provide further evidence of respiratory muscle dysfunction in patients with this disease. Respiratory muscle endurance needs now to be related to symptoms and the effects of treatment and respiratory muscle training should also be explored.     

Exercise-induced increases in oxidized low-density lipoprotein are associated with adverse outcomes in chronic heart failure

BackgroundOxidative stress is an important pathophysiologic feature in chronic heart failure (CHF) and may in part result from the inability to counteract acute surges of circulating oxidant products. Oxidized low-density lipoprotein (oxLDL) is an emerging prognostic marker in CHF. Accordingly, we investigated the effect of exercise-induced oxidative stress on circulating levels of oxLDL and its association with clinical outcomes in CHF.Methods and ResultsPlasma levels of oxLDL and low-density lipoprotein cholesterol (LDL-c) were measured at rest and after maximal exercise in 48 subjects with CHF and 12 healthy controls. Subjects with CHF had a higher baseline oxLDL (77.7 ± 3.2 U/L vs 57.9 ± 5.0 U/L, P = .01) and a higher baseline oxLDL/LDL-c ratio (0.87 ± 0.04 vs 0.49 ± 0.04, P ≤ .001). Exercise induced an increase in oxLDL in subjects with CHF (77.7 ± 3.2 U/L to 85.3 ± 3.0 U/L, P ≤ .001) but not in controls (57.9 ± 5.0 to 61.4 ± 5.5, P = .17). In 39 subjects for whom follow-up data were available, an increase in oxLDL of more than 11.0 U/L was associated with an increased risk to meet a combined end point of death and need for ventricular assist device or heart transplant during a 19-month follow-up period (hazard ratio 8.6; 95% confidence interval 1.0–73.8, P = .05); this remained significant when adjusted for peak oxygen consumption, left ventricular ejection fraction, New York Heart Association class, sex, and age (hazard ratio 46.6, 95% confidence interval 1.5–1438.1, P = .02).ConclusionPlasma oxLDL and the oxLDL/LDL-c ratio are elevated in subjects with CHF. Whether assessment of oxLDL during maximal exercise allows early identification of subjects at highest risk for adverse outcomes should be systematically investigated.     

Difficulties in maintaining potassium homeostasis in patients with heart failure

Potassium (K) concentration plays a significant role in cell metabolism and membrane excitability. The imbalance of serum potassium is important because it can lead to life-threatening events. Potassium balance may be lost both through the neurohormonal mechanisms involved in cardiovascular diseases and through the drugs used in the treatment of this illness. Avoiding both hypo- and hyperkalemia is beneficial in several cardiovascular diseases, especially heart failure. Electrolyte abnormalities are frequently seen complications in subjects with heart failure. Malignant ventricular arrhythmias and sudden cardiac death are particularly feared complications in K+ instability.     

Exercise endpoints in patients with chronic heart failure

BACKGROUND: Peak oxygen consumption (V(O(2))) is a powerful predictor of outcome in patients with chronic heart failure. This is not a test that is readily clinically available. We therefore sought to establish a method of assessing peak V(O(2)) from non-invasively acquired data. METHODS: We analysed the results from incremental treadmill exercise tests in 60 patients [aged 59.0 (S.D. 12.4) years] with chronic heart failure or left ventricular dysfunction [left ventricular ejection fraction (29.6 (15.2)%)] and 52 control subjects [aged 36.7 (12.3)]. Metabolic gas exchange during exercise was measured with a respiratory mass spectrometer. Heart rate and blood pressure were measured. RESULTS: Peak V(O(2)) was lower in patients than controls [19.9 (7.7) ml/kg/min vs. 38.3 (9.0), P<0. 001]. Exercise time (r=0.84, P<0.001), heart rate at peak exercise (r=0.63, P<0.0001), change in heart rate (r=0.72, P<0.0001), rate pressure product at peak exercise (r=0.64, P<0.0001) and change in systolic blood pressure (r=0.31, P=0.002) all correlated with peak V(O(2)). In a stepwise regression model, exercise time was the most powerful predictor of peak V(O(2)) (r(2)=0.79). The only additional independent variable was change in heart rate from rest to peak exercise, which increased r(2) to 0.80. In a survival analysis, measured peak V(O(2)) and the peak V(O(2)) estimated from exercise time and change in heart rate had similar predictive power. CONCLUSIONS: In this preliminary study, peak V(O(2)) can be estimated from non-invasively acquired parameters. Estimated peak V(O(2)) and measured peak V(O(2)) have similar predictive power for outcome. Further work is necessary to see if estimated peak V(O(2)) is widely applicable in a clinical setting.     

慢性心力衰竭的运动康复治疗

心力衰竭（心衰）是一组临床综合征．是各种心脏病发展的终末阶段。随着老龄化社会的到来,心衰患者增多。我国35～74岁的成年人中心衰的患病率为0．9％,按此推算约有400万心衰患者。心衰使患者的运动耐量下降,体力活动受限,生活质量下降,病情急剧恶化,给医疗保障系统和患者家庭造成了沉重的经济和社会负担。即使在医疗条件较好的发达国家,慢性心力衰竭确诊后患者的平均生存时间也很短,男性为1．7年,女性为3．2年,两者的5年生存率仅为25％和38％。所以,心衰治疗已经成为21世纪心脏病学最大的挑战之一。     

慢性心力衰竭患者动态心率震荡分析

目的：探讨窦性心率震荡（HRT）的新测量指标动态心率震荡（TD）及HRT测量指标震荡初始（TO）、震荡斜率（TS）在慢性心力衰竭（CHF）患者中的变化,分析其与传统高危预测指标的相关性及预测CHF患者价值。方法纳入2011年9月~2013年6月在天津市胸科医院就诊的CHF患者120例作为CHF组,同期纳入非器质性心脏病患者30例作为对照组,将CHF组按NYHA分级分为轻度CHF组（心功能Ⅰ~Ⅱ级,n=72）和中重度CHF组（心功能Ⅲ~Ⅳ级,n=48）。所有患者行放射免疫法检测B型脑钠肽（BNP）水平,超声心动图检查左房内径（LAD）、左室舒张末径（LVEDD）、左室射血分数（LVEF）;24 h动态心电图检查记录心率变异性时域（SDNN）、平均心率、室性早搏前心率（HRVPC）以及RR间期,计算HRT指标（包括TO、TS和TD）。比较各组之间的差异,分析HRT各指标与年龄、性别、LAD、LVEDD、LVEF、BNP的相关性。结果与对照组相比,CHF组SDNN缩短[（95.67±30.22） msvs.（131.65±20.71）ms],TO和TD更高[TO：（-1.50±2.71）%vs.（0.61±1.95）%;TD：（0.012±0.004）mm/RRIvs.（0.063±0.031）mm/RRI],LAD和LVEDD更高[LAD：（36.11±2.24）mmvs.（47.65±2.13）mm;LVEDD：（43.65±7.33）mmvs.（62.13±8.70）mm],BNP明显升高[（80.05±32.30）pg/ml vs.（941.00±139.17）pg/ml],TS和LVEF更低[TS：（12.13±3.67）vs.（6.80±5.33）;LVEF：（67.30±5.21）% vs.（38.22±12.75）%],而且随着CHF程度的加重,上述改变更加明显。CHF组TO与TS、LVEF、SDNN负相关（P＜0.05）;TS与SDNN正相关（P＜0.05）,与HRVPC、BNP负相关（P＜0.05）。结论 CHF患者HRT明显减弱,其中TO和TS均受到SDNN的影响,而TD与HRVPC、SDNN、LVEF、BNP指标无关。     

Urotensin II in patients with chronic heart failure

BACKGROUND: Human Urotensin II (hU-II) is the most potent vasoconstrictor known to date. HU-II receptors are predominant in the human heart and arterial vessels, suggesting hU-II to be of importance as a cardiovascular mediator. METHODS: We studied 32 consecutive patients (60+/-12 years) with chronic heart failure (CHF) and 10 control subjects (54+/-12 years, n.s.) with cardiopulmonary exercise testing. Blood samples for the measurement of plasma hU-II and big-endothelin-1 (big-ET1) were obtained at rest and at peak exercise. RESULTS: Peak VO(2) was significantly higher in controls than in CHF patients (19.8+/-3.8 vs. 14.7+/-3.6 ml min(-1) kg(-1), P<0.001). Big-ET1 levels were increased in CHF compared to controls at rest (2.8+/-1.8 vs. 1.7+/-0.1 fmol/ml, P<0.01) and at peak exercise (2.7+/-1.7 vs. 1.6+/-0.2 fmol/ml, P<0.005). HU-II concentrations were comparable in patients with CHF and controls at rest (2990+/-1104 vs. 3290+/-508 pg/ml, n.s.) and peak exercise (3063+/-1185 vs. 3213+/-1188 pg/ml, n.s.). Resting hU-II levels demonstrated no correlation with peak VO(2) in controls or CHF patients. CONCLUSIONS: The measurement of circulating plasma levels of hU-II does not seem to be very helpful in studying the effects of hU-II in human cardiovascular regulation. A local paracrine or autocrine mediator effect of hU-II in CHF is possible.     

Aldosterone blockade in patients with chronic heart failure

Aldosterone blockade has been shown to be effective in reducing mortality in patients who have severe heart failure because of systolic left ventricular dysfunction (SLVD) and those who have heart failure and SLVD post-myocardial infarction. Aldosterone blockade also may be beneficial in patients who have New York Heart Association class II heart failure, asymptomatic left ventricular dysfunction, and heart failure with preserved or normal left ventricular function. Considering the beneficial effects of aldosterone blockade on improving nitric oxide availability, endothelial function, and atherosclerosis, it can also be postulated that an aldosterone blockade would add to the benefits of an angiotensin-converting enzyme inhibitor in patients who have coronary artery disease. However, these hypotheses must be confirmed in well-designed, large-scale, prospectively randomized studies.