Stable Chronic Congestive Heart Failure Research Articles

The SERVE-HF safety notice in clinical practice – experiences of a tertiary sleep center

BackgroundIn May 2015, the results of the SERVE-HF trial – addressing adaptive servoventilation (ASV) in chronic congestive heart failure (CHF) patients with central sleep apnea (CSA) – prompted a field safety notice. It was recommended to identify CHF patients treated with ASV and to advise the discontinuation of the treatment. We aimed to analyze the identification process and effect of ASV discontinuation on affected patients. Methods126 patients treated with ASV on May 13th, 2015 at our institution were retrospectively analyzed. Treatment decisions, effect of ASV discontinuation and clinical course were followed for a year. Patients on ASV with CHF were compared to those without CHF. ResultsThe risk criteria of the safety notice were fulfilled by 10.3% of patients (13/126). Additional echocardiographies were performed in 38%. ASV was discontinued in 93% of patients without adverse events (emergency hospitalization in n = 1). CSA reappeared immediately. Day- or nighttime symptoms were reported by 61%. Symptomatic patients were started on alternative treatments. CHF and non-CHF patients differed in cardiac function and type of SDB. CHF patients had shorter overall treatment duration. Compliance to ASV was similar in both groups with a median usage of 412 min (269; 495)/night in the CHF group and 414.5 min (347; 480) in the non-CHF group. ConclusionIdentification of patients “at risk” is feasible but outcome of discontinuation of ASV cannot be evaluated based on these data. ASV withdrawal in patients with stable chronic CHF and CSA leads to an immediate return of sleep disordered breathing. Symptomatic patients may ask for alternative treatment options.

Interdependence of Cardiac and Endothelial Function in Patients with Symptomatic Chronic Heart Failure of Nonischemic Etiology

Endothelial dysfunction has emerged as a therapeutic target in patients with chronic congestive heart failure (CHF). Endothelial dysfunction may impair left ventricular (LV) systolic function by increasing systemic vascular resistance. Conversely, LV impairment may negatively impact endothelial function by reducing shear stress and vascular nitric oxide (NO) bioavailability. This study was undertaken to determine the association between LV and endothelial function in patients with CHF. Echocardiographic and vascular ultrasound studies were performed to measure left ventricular ejection fraction (LVEF) and brachial artery flow-mediated vasodilatation (FMD) in 30 subjects with stable New York Heart Association class II-III CHF. All patients received optimal medical therapy. LVEF averaged 25 +/- 9% and brachial artery FMD 1.3 +/- 2.4%. LVEF strongly correlated with FMD among all patients (r = 0.64, P< 0.001) and among those patients with nonischemic (n = 19, r = 0.66, P = 0.002), but not in patients with ischemic etiology (n = 11, r = 0.27, P = 0.42). LVEF and endothelium-dependent NO vasodilatation are strongly correlated in stable ambulatory patients with systolic CHF of nonischemic etiology. Our study underscores the mutual interaction between central cardiac and peripheral vascular function, thus strengthening a mechanistic rationale for the systemic beneficial effects of interventions targeting either the heart or the vascular endothelium in CHF.

Heart rate increment analysis is not effective for sleep-disordered breathing screening in patients with chronic heart failure

Frequency domain analysis of heart rate variation has been suggested as an effective screening tool for sleep-disordered breathing (SDB) in the general population. The aim of this study was to assess this method in patients with chronic congestive heart failure (CHF). We included prospectively 84 patients with stable CHF, left ventricular ejection fraction (LVEF) <45% and sinus rhythm. The patients underwent polygraphy to measure the apnoea/hypopnoea index (AHI) and simultaneous Holter electrocardiogram monitoring to measure the power spectral density of the very low frequency component of the heart rate increment, expressed as the percentage of total power spectral density [% very low frequency increment (%VLFI)]. %VLFI could be determined in 54 patients (mean age, 52.8 +/- 12.3 years; LVEF, 33.5 +/- 9.8%). SDB defined as AHI > or =15 h(-1) was diagnosed in 57.4% of patients. Percent VLFI was not correlated with AHI (r = 0.12). Receiver-operating characteristic curves constructed using various AHI cut-offs (5-30 h(-1)) failed to identify a %VLFI cut-off associated with SDB. The 2.4% VLFI cut-off recommended for the general population of patients with suspected SDB had low specificity (35%) and low positive and negative predictive values (35% and 54%, respectively). Heart rate increment analysis has several limitations in CHF patients and cannot be recommended as an SDB screening tool in the CHF population.

H013 Heart rate variability analysis is not effective for sleep-apnoea-syndrome screening in patients with chronic heart failure

Frequency-domain analysis of heart rate variation has been suggested as an effective screening tool for sleep apnoea syndrome (SAS) in the general population. The aim of this study was to determine whether this method could be effective in patients with chronic congestive heart failure (CHF). 84 patients with stable CHF, left ventricular ejection fraction (LVEF) <45 %, and sinus rhythm were included prospectively. Patients underwent simultaneous polygraphy to measure apnoea/hypopnoea index (AHI) and ECG Holter monitoring to measure the power spectral density of the very low frequency component of the heart rate increment, expressed as the percentage of total power spectral density (% VLFI). VLFI could be determined in 54 patients (mean age 52.8+/-12.3 years and LVEF 33.5+/-9.8 %). SAS defined as AHI >=15•h-1 was diagnosed in 57.4 % of patients. % VLFI was not correlated with AHI (R = 0.12). Receiver operating characteristic curves constructed using various AHI cut-offs (5 to 30.h-1) failed to identify a % VLFI cut-off associated with SAS. The 2.4 % VLFI cut-off recommended for the general population of patients with suspected SAS had low values for specificity (35 %), positive and negative predictive value (35 % and 54 % respectively). Heart rate increment analysis demonstrated several limitations in CHF. At this time, HRV methodology could not be proposed as the first step of SAS screening in CHF population.

Prognostic value of cardiac troponin T in patients with both acute and chronic stable congestive heart failure: comparison with atrial natriuretic peptide, brain natriuretic peptide and plasma norepinephrine

Background The prognostic value of cardiac troponin T (cTn-T) in a mixture of patients with both acute and chronic congestive heart failure (CHF), simultaneously assessed and compared with neurohormonal factors, has not yet been thoroughly evaluated. Thus, we focused on the prognostic value of cTn-T in comparison with atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and plasma norepinephrine (PNE) in this population. Methods Prognostic correlates of elevation of cTn-T, ANP, BNP, PNE were analyzed in 63 acute and chronic CHF patients followed up to record worsening CHF and cardiac death. Results cTn-T (≥0.03 μg/L) was found in 17.4% (11 of 63) of patients. cTn-T correlated with ANP, BNP, PNE. Acute CHF patients were more positive for cTn-T and BNP. In our cohort, neither cTn-T (≥0.03 μg/L) nor PNE were associated with increased mortality and worsening HF in CHF patients. After adjustment, BNP was the only independent predictor of cardiac events (RR, 3.23; p=0.01). Conclusions BNP emerged as the only independent predictor of cardiac events in a mixture of patients with both acute and chronic CHF, suggesting that it is the analyte that best reflects long-term prognosis in a diverse population enrolled to mirror the “real world” situation.

Prognostic value of interleukin-6, plasma viscosity, fibrinogen, von Willebrand factor, tissue factor and vascular endothelial growth factor levels in congestive heart failure.

Congestive heart failure (CHF) carries a poor prognosis with a high mortality rate, frequent hospitalizations and increased risk of thrombotic complications such as stroke. Cytokines may contribute to the progression and prothrombotic state of CHF, including the pro-inflammatory interleukin-6 (IL-6) and the pro-angiogenic vascular endothelial growth factor (VEGF), both of which are raised in CHF. The procoagulant properties of both cytokines may be mediated via tissue factor (TF), a potent clotting activator. We hypothesized that plasma levels of these markers, as well as levels of plasma viscosity, fibrinogen, soluble P-selectin and von Willebrand factor (markers of abnormal rheology, clotting, platelet activation, and endothelial damage, respectively) will be useful in predicting morbidity and mortality in chronic stable CHF. One hundred and twenty consecutive out-patients with chronic stable CHF (92 males; mean [SD] age 64 [11] years, mean [SD] left ventricular ejection fraction of 29 [6]%) were recruited and followed for 2 years during which 42 patients reached a clinical end-point of all-cause mortality and cardiovascular hospitalizations, including stroke and myocardial infarction. Plasma IL-6 (P=0.003) and TF (P=0.013) levels, but not other research indices, were higher in those who suffered events compared with those without events. Predictors of end-points were high (> or =median) TF (P=0.011), and IL-6 (P=0.023) levels, as well as the lowest quartile of a left ventricular ejection fraction (P=0.007). A strong correlation was present between TF and IL-6 levels (r=0.59; P<0.0001) and with VEGF levels (r=0.43; P<0.0001). IL-6 and TF are predictors of poor prognosis in chronic CHF, raising the hypothesis that IL-6 may contribute to the progression and thrombotic complications of CHF via its actions on TF expression. Although VEGF did not independently predict outcome in chronic CHF, the possibility arises that it may act with IL-6 to induce TF expression.

Interleukin-6, tissue factor and von Willebrand factor in acute decompensated heart failure: relationship to treatment and prognosis.

Arterial thrombotic and thromboembolic complications are increased in congestive heart failure (CHF), and are a particular problem in acute decompensated heart failure, which carries a poor prognosis. As interleukin-6 (IL-6) has been shown to induce the potent procoagulant tissue factor (TF) in experimental models, we hypothesized that the pro-inflammatory IL-6 may be one mechanism contributing to thrombosis in heart failure, mediated via endothelial expression of TF on activated/damaged cells [indicated by plasma von Willebrand factor (vWF)]. Seventy-seven patients (67% men, New York Heart Association class III-IV, 87%) with acute CHF were recruited, and were compared with 53 chronic stable CHF patients in sinus rhythm (66% men, New York Heart Association class III-IV, 2%) and 37 healthy controls (68% men). Acute CHF patients in sinus rhythm had elevated baseline levels of IL-6 (P < 0.0001), TF (P = 0.041) and vWF (P < 0.0001) (all measured by enzyme-linked immunosorbent assay) compared with both chronic CHF and healthy control groups. A correlation exists in acute CHF between baseline TF and IL-6 (Spearman r = 0.64, P < 0.0001). After 3 months treatment, with control or alleviation of heart failure symptoms in 40 patients, there was a fall in levels of IL-6 (P < 0.0001) and vWF (P < 0.0001), but levels still remained significantly higher than healthy controls. Patients who died at 6 months follow-up also had higher baseline levels of IL-6 (P = 0.008), TF (P = 0.037) and vWF (P = 0.039) when compared with those who remained alive. Elevated IL-6 may contribute to the thrombotic and thromboembolic complications in acute heart failure, in a process mediated via increased TF and vWF. Improvement of symptoms and plasma markers after treatment of acute CHF and prediction of prognosis by the markers may be useful in the clinical setting.

Vascular endothelial growth factor and soluble P-selectin in acute and chronic congestive heart failure

Because congestive heart failure (CHF) is characterized clinically by tissue hypoxia, we hypothesized that there would be evidence of neovascularization, possibly resulting from this process. To test this, we measured levels of vascular endothelial growth factor (VEGF), associated with angiogenesis, in the plasma of patients with varying degrees of CHF (presenting acutely and in the chronic phase) and compared levels with those in healthy controls. To test the hypothesis of a link between VEGF and platelet activation and a tendency to hypercoagulability in CHF, 1,2 we also measured plasma levels of fibrinogen and soluble P-selectin, because these markers of coagulation and platelet activation have previously been shown to increase in patients with chronic CHF. 2 Our methods to testing these hypotheses were cross sectional (comparing patients with acute and chronic CHF with healthy controls), interventional (examining markers before and after successful treatment of acute CHF), and using a follow-up approach (at which time we questioned whether or not plasma markers could predict those at risk of mortality). ••• We recruited consecutive patients admitted with acute CHF secondary to impaired left ventricular systolic function, which was documented as an ejection fraction 40%, either by echocardiography, radionuclide imaging, or left ventriculography on admission, or within the previous 6 months. Patients were excluded from the study for the following criteria: concomitant acute coronary syndromes; infection or pyrexial illness; recent (3 months) myocardial infarction or stroke; unstable angina or ventricular arrhythmias; chronic and systemic illnesses including renal failure, hepatic impairment, cancer, and inflammatory connective tissue disease; and use of oral steroids or hormone replacement therapy. Baseline results from patients with acute CHF (i.e., subjects presenting acutely with severe symptomatic disease) were compared with 2 age- and gender-matched control groups; these were outpatients with chronic stable CHF in sinus rhythm (chronic CHF) and healthy control subjects recruited from among healthy hospital staff and from subjects attending the hospital for hernia repairs, varicose vein procedures, or other relatively minor operations. Subjects with CHF were classified according to the New York Heart Association (NYHA) criteria, with class I to II being no or mild symptoms and class III to IV being moderate to severe symptoms. Left ventricular ejection fraction was estimated using transthoracic M-mode echocardiography. All healthy controls had no clinical evidence of vascular, metabolic, neoplastic, diabetic, or in flammatory disease on careful history, examination, and routine laboratory tests. Blood tests were performed in patients with acute decompensated CHF between days 1 and 7 after hospital admission, and again at 3 months after standard treatment for heart failure according to local guidelines. 3 Patients were followed up for clinical end points that consisted of all-cause mortality and hospitalizations for stroke, myocardial infarction, thromboembolism, unstable angina, and revascularization for up to 6 months. Citrated plasma and serum were obtained from

Hormonal profile in patients with congestive heart failure

Background: Recent progress has been made in the understanding of the cellular and molecular mechanisms of growth hormone action and of its effects on cardiac tissue. The aim of this study was to measure growth hormone concentrations, along with various other hormones, in patients with stable chronic congestive heart failure due to idiopathic dilated cardiomyopathy. Methods: The study included 23 ambulatory men, 51.2±9.3 years of age, on standard medical therapy for heart failure due to idiopathic dilated cardiomyopathy. All patients underwent clinical and laboratory evaluations, including echocardiogram, radionuclide ventriculography, right heart catheterization, coronary angiography, and right ventricular endomyocardial biopsy. Serum or plasma concentrations of growth, thyroid, sex and adrenal hormones were measured in all patients and compared with those found in 20 age-matched healthy men. Results: Growth hormone, insulin-like growth factor I, and free testosterone values in patients with idiopathic dilated cardiomyopathy and heart failure were 0.37±0.2 ng/ml, 123.7±50 ng/ml and 48.6±23.8 pmol/l, respectively, versus 0.5±0.4 ng/ml ( P<0.01), 236.3±66.4 ng/ml ( P<0.001) and 105±17 pmol/l ( P<0.01), respectively, in the healthy age-matched individuals. All other hormone concentrations were comparable in both groups. Conclusions: Chronic heart failure due to idiopathic dilated cardiomyopathy is associated with a significant decrease in growth hormone, insulin-like growth factor I, and testosterone concentrations, probably due to chronic disease.

Relationship of carbon dioxide tension in arterial blood to pulmonary wedge pressure in heart failure.

Hypocapnia contributes to the genesis of Cheyne-Stokes respiration and central sleep apnoea in patients with congestive heart failure (CHF) and is associated with increased mortality. However, the cause of hypocapnia in patients with chronic stable CHF is unknown. Since pulmonary congestion can induce hyperventilation via stimulation of pulmonary vagal afferents, the present study tested the hypothesis that in patients with CHF (carbon dioxide tension in arterial blood (Pa,CO2)) is inversely related to pulmonary capillary wedge pressure (PCWP), and that alterations in PCWP would cause inverse changes in Pa,CO2. In 11 CHF patients undergoing diagnostic cardiac catheterization, haemodynamic variables and arterial blood gas tensions were measured simultaneously at baseline. In three patients, these measurements were repeated after coronary angiographic dye infusion and nitroglycerine infusion. At baseline, Pa,CO2 correlated inversely with PCWP (r=-0.80, p=0.003). In the three patients in whom multiple measurements were made, acute alterations in PCWP caused inversely proportional changes in Pa,CO2. The present study concludes that in patients with congestive heart failure, pulmonary capillary wedge pressure is an important determinant of carbon dioxide tension in arterial blood. These findings imply that hypocapnia in patients with chronic stable congestive heart failure is a respiratory manifestation of elevated left ventricular filling pressures.

Beta-blockers in congestive heart failure. A Bayesian meta-analysis.

Congestive heart failure is an important cause of patient morbidity and mortality. Although several randomized clinical trials have compared beta-blockers with placebo for treatment of congestive heart failure, a meta-analysis quantifying the effect on mortality and morbidity has not been performed recently. The MEDLINE, Cochrane, and Web of Science electronic databases were searched from 1966 to July 2000. References were also identified from bibliographies of pertinent articles. All randomized clinical trials of beta-blockers versus placebo in chronic stable congestive heart failure were included. A specified protocol was followed to extract data on patient characteristics, beta-blocker used, overall mortality, hospitalizations for congestive heart failure, and study quality. A hierarchical random-effects model was used to synthesize the results. A total of 22 trials involving 10 135 patients were identified. There were 624 deaths among 4862 patients randomly assigned to placebo and 444 deaths among 5273 patients assigned to beta-blocker therapy. In these groups, 754 and 540 patients, respectively, required hospitalization for congestive heart failure. The probability that beta-blocker therapy reduced total mortality and hospitalizations for congestive heart failure was almost 100%. The best estimates of these advantages are 3.8 lives saved and 4 fewer hospitalizations per 100 patients treated in the first year after therapy. The probability that these benefits are clinically significant (>2 lives saved or >2 fewer hospitalizations per 100 patients treated) is 99%. Both selective and nonselective agents produced these salutary effects. The results are robust to any reasonable publication bias. beta-Blocker therapy is associated with clinically meaningful reductions in mortality and morbidity in patients with stable congestive heart failure and should be routinely offered to all patients similar to those included in trials.

Hemodynamic Effects of Noninvasive Bilevel Positive Airway Pressure on Patients With Chronic Congestive Heart Failure With Systolic Dysfunction

Noninvasive positive airway pressure may play a significant role in treating patients with congestive heart failure (CHF). We tested our hypothesis that noninvasive bilevel positive airway pressure improves left ventricular performance in patients with chronic CHF secondary to severe systolic dysfunction. To determine the cardiac performance of patients using bilevel positive airway pressure, and to describe the hemodynamic effects of bilevel positive airway pressure and its use as a therapeutic adjunct in these patients. Prospective, cohort, nonrandomized study. Outpatient medicine clinic. Fourteen patients (9 men and 5 women) with stable chronic CHF with left ventricular ejection fraction < or =35%; mean age was 60.6 years (range, 43 to 87 years). Bilevel positive airway pressure via nasal mask at an inspiratory pressure of 5 cm H(2)O and an expiratory pressure of 3 cm H(2)O on spontaneous mode at room air for 1 h. Myocardial performance and changes were measured using clinical and echocardiographic parameters. Baseline clinical and echocardiographic parameters were compared with the same parameters after 1 h of bilevel positive airway pressure. Statistically significant (p<0.05, Wilcoxon matched pair signed-rank test) decreases were noted in these mean values: systolic BP from 136.21 to 124.14 mm Hg (p = 0.008), heart rate from 85.07 to 74.71 beats/min (p = 0.002), respiratory rate from 23.07 to 15.43 breaths/min (p = 0.001), and systemic vascular resistance from 1671. 46 to 1236.27 dyne. s. cm(3) (p = 0.001). Statistically significant increases were noted in these mean values: cardiac output from 5.09 to 6.37 L/min (p = 0.004), ejection fraction from 28.71% to 34.36% (p = 0.001), and end-diastolic volume from 224.36 to 246.21 mL (p = 0.045). Bilevel positive airway pressure has excellent potential for improving left ventricular performance of patients with chronic CHF secondary to severe systolic dysfunction.

Association between hemodynamic impairment and cheyne-stokes respiration and periodic breathing in chronic stable congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy

Irregular breathing occurs frequently in patients with congestive heart failure (CHF) both during daytime and nighttime. Many factors are involved in the genesis of these breathing abnormalities, but the role of the hemodynamic impairment remains controversial. This study investigated the relation between worsening ventricular function and the frequency of respiratory disorders in patients with mild to severe CHF. One hundred fifty patients with CHF (mean age 53 ± 8 years, left ventricular (LV) ejection fraction 26 ± 7, in New York Heart Association [NYHA] classes II to IV, and who underwent stable therapy for ≥2 weeks) were studied. Analysis of instantaneous lung volume signal and arterial oxygen saturation during awake daytime revealed a normal respiratory pattern in 63 patients, whereas 87 had a persistent alteration of breathing, with a typical Cheyne-Stokes respiration (CSR) in 42 and periodic breathing (PB [oscillation of tidal volumes without apnea]) in 45 patients. Patients with PB and CSR showed a more pronounced hemodynamic impairment with a significantly reduced cardiac index, an increased pulmonary arterial wedge pressure, and a longer lung-to-ear circulation time (LECT) compared with patients with normal respiratory patterns. In a logistic regression model that included all of the variables significantly associated with breathing disorders, cardiac index and LECT emerged as the major determinants of CSR. In those patients with LECT ≥30 seconds (upper quartile) and cardiac index ≤1.9 L/min/m 2 (lower quartiles), the incidence of CSR was significantly higher (69%) than in patients with lower LECT and higher cardiac index (14%, p <0.001). In conclusion, abnormalities of breathing activity during daytime are significantly associated with a prolonged circulation time and a more severe impairment of systolic and diastolic LV indexes.

Hemodynamic responses during leg press exercise in patients with chronic congestive heart failure

To increase muscle mass and strength in patients with chronic congestive heart failure (CHF), there is a need for implementing resistance exercises in exercise training programs. This study sought to assess the safety of rhythmic strength exercise with respect to left ventricular function in 9 patients with stable CHF, compared with 6 stable coronary patients with mild left ventricular dysfunction (control group). With use of right-sided catheterization, changes in left ventricular function were assessed during double leg press exercise at loads of 60% and 80% of maximum voluntary contraction. The exercise sessions lasted 14 minutes each, divided into work and recovery phases of 60/120 seconds. In CHF, during exercise at a 60% load, there was a significant increase in heart rate (mean ± SEM 90 ± 4 beats/min; p <0.05), mean arterial blood pressure (95 ± 3 mm Hg; p <0.01), diastolic pulmonary artery pressure (20.2 ± 2.7 mm Hg; p <0.01), and cardiac index (3 ± 0.3 L/m 2/min; p <0.05). Additionally, during leg press exercise at an 80% load, there was a significant decrease in systemic vascular resistance (1,086 ± 80 dynes · s · cm −5; p <0.001), an increased cardiac index (3.4 ± 0.1; p <0.001), and left ventricular stroke work index (75 ± 5 g · m/m 2; p <0.01), suggesting enhanced left ventricular function. Compared with controls, in CHF the magnitude of changes in hemodynamic parameters during exercise, demonstrated at a 60% load, was significantly smaller (systemic vascular resistance: [mean] 1,613 → 1000 vs 1472 → 1,247 dynes · s · cm −5; cardiac index: 2.4 → 3 vs 2.8 → 4.4 L/m 2/min, and stroke work index: 60 → 69 vs 114 → 155 g · m/m 2; p <0.05 each). Nevertheless, changes indicated an enhanced contractile function of the left ventricle in CHF. This study demonstrates stability of left ventricular function during resistance exercise in well-compensated CHF patients with optimal drug therapy, as well as the appropriateness of the chosen mode and intensity applied as these factors relate to cardiovascular stress. This conclusion cannot be extrapolated to patients with less well-compensated heart failure, or to more protracted resistance training.

Regulation of regional norepinephrine spillover in heart failure: The effect of angiotensin ii and β-adrenergic agonists in the forearm circulation

Background: Prejunctional receptors for angiotensin II (A-II) and norepinephrine (NE) have been reported to facilitate NE release. If operative in patients with congestive heart failure (CHF), such receptors could participate in positive feedback cycles amplifying sympathoactivation. Methods and Results: A-II and isoproterenol (ISO) would increase regional NE spillover via facilitation of presynaptic release of NE in the forearm circulation of patients with chronic stable CHF. A-II, ISO, and nitroprusside (NP) were sequentially infused into the brachial arteries of 10 patients with chronic stable CHF, which was attributed to dilated cardiomyopathy. Forearm blood flow (FBF) was measured via plethysmography and regional spillover of NE was measured by using the isotope dilution method of Esler. A-II (5 ng/min) produced a nonsignificant decline in FBF (1.87 ± 0.14 to 1.46 ± 0.1 mL/100 g/min, P = .07) and did not change regional NE spillover (418 ± 128 to 409 ± 121 ng/min). ISO increased FBF from 1.6 ± 0.12 to 4.3 ± 0.7 mg/100 g/min ( P < .001). Regional NE spillover increased from 337 ± 86 to 856 ± 300 ng/min ( P < .001). Venous NE and regional extraction of NE did not change. NP increased FBF from 2.0 ± 0.3 to 6.3 ± 1.2 mL/100 g/min ( P < .001; P = NS v change with ISO) and also increased regional NE spillover (301 ± 99 to 712 ± 288 ng/min, P < .001; P = NS v change with ISO). As with ISO, venous NE and extraction of NE were not altered. Conclusions: Mild vasoconstrictor infusions of A-II do not increase regional NE spillover in the forearm circulation of patients with CHF. The β-adrenergic agonist ISO does increase regional spillover, but the effect seems to be primarily related to flow rather than presynaptic stimulation of NE release. These data argue against an important positive feedback loop involving A-II and NE on sympathoactivation, at least with the dosages of the agonists studied and in the limb circulation in chronic stable CHF.

Comparison of left ventricular function during interval versus steady-state exercise training in patients with chronic congestive heart failure

This study sought to assess the safety of interval exercise training in patients with chronic congestive heart failure (CHF) with respect to left ventricular (LV) function. For effective rehabilitation in CHF, both aerobic capacity and muscle strength need to be improved. We have previously demonstrated in both coronary artery bypass surgery and patients with CHF that interval exercise training (IET) offers advantages over steady-state exercise training (SSET). However, because LV function during IET has not yet been studied, the safety of this method in CHF remains unclear. To assess LV function during IET and SSET, at the same average power output, 11 patients with stable CHF were compared with 9 stable coronary patients with minimal LV dysfunction (control group). Using first-pass radionuclide ventriculography, changes in LV function were assessed during work versus recovery phases, at temporally matched times between the fifth and sixteenth minute of IET and SSET. In CHF during IET, there were no significant variations in the parameters measured during work and/or recovery phases. During the course of both IET and SSET, there was a significant increase in LV ejection fraction (5 vs 4 U; p <0.05 each), accompanied by increased heart rate (6 vs 8 beats/min; p <0.05 each) and cardiac output (2.4 vs 1.8 L/min; p <0.01 and p <0.05). In CHF, the magnitude of change in LV ejection fraction during IET was similar to that seen in controls. Both LV ejection fraction and the clinical status in patients with CHF remained stable during IET. Because IET appears to be as safe as SSET with respect to LV function, IET can be recommended for exercise training in CHF to apply higher peripheral exercise stimuli and with no greater LV stress than during SSET.

Undetected cardiogenic shock in patients with congestive heart failure presenting to the emergency department

The purpose of this study was to examine the use of lactic acid levels and continuous central venous oxygen saturation (central venous oximetry) to stratify and treat patients with acutely decompensated end-stage chronic congestive heart failure (CHF) presenting to the emergency department. This prospective, convenience, non-outcome study was performed at an urban tertiary care hospital. Patients with end-stage CHF with an ejection fraction <30% presenting in decompensated CHF were eligible for the study. Patients were assessed using the Killip classification and New York Heart Association criteria. After lactic acid levels were obtained, patients were managed according to a standardized protocol guided by central venous oximetry. The patients were divided into high lactic acid (n = 22), low lactic acid (n = 5), and control groups (stable patients presenting to a cardiology clinic, n = 17) for comparison. There was no statistical difference in vital signs, or Killip and New York Heart Association criteria among the 3 groups. Central venous oxygen saturation was significantly lower in the high lactic acid group (32 ± 12%) than in the normal lactic acid (51 ± 13%) and control groups (60 ± 6%) (p <0.001). After treatment there was a significant decrease in lactic acid (−3.65 ± 3.65 mM/L) and an increase in central venous oxygen saturation (32 ± 13%) in the high lactic acid group compared with the normal lactic acid group (p <0.001). A significant subset of patients with decompensated end-stage CHF present to the emergency department in occult shock and are clinically indistinguishable from patients with mildly decompensated CHF and stable CHF. Once identified, these patients require aggressive alternative management and disposition. Further study is necessary to identify whether this intervention impacts morbidity, mortality, and health care resource consumption.

Valsartan in heart failure patients previously untreated with an ACE inhibitor

Objective: To evaluate the effect on cardiac hemodynamic parameters of valsartan in patients with chronic stable congestive heart failure previously untreated with ACE inhibitors. Methods: After a 2 to 4 week run-in period, 116 adult outpatients were randomized to receive valsartan 40, 80 or 160 mg twice daily, the ACE inhibitor lisinopril 5/10 mg once daily, or placebo. At baseline and after 28 days of treatment, cardiac hemodynamic parameters were measured. Tolerability was assessed by adverse events and by any changes in systolic or diastolic blood pressure, body weight, heart rate, and routine laboratory parameters. Results: For the 12 hour time point (trough), all doses of valsartan reduced mean pulmonary capillary wedge pressure (statistically significant for valsartan 40 mg and 160 mg), decreased systemic vascular resistance (statistically significant for all three valsartan doses and for lisinopril at peak and trough), and increased cardiac output (statistically significant for all three valsartan doses at peak, and for 80 and 160 mg at trough). There were no clinically relevant effects on any safety parameters. Conclusions: Valsartan has beneficial effects on cardiac hemodynamics, and is generally well tolerated in patients with congestive heart failure not taking ACE inhibitors.

Skeletal Muscle Oxygenation and Oxygen Uptake Kinetics Following Constant Work Rate Exercise in Chronic Congestive Heart Failure

The aim of the present study was to determine the kinetics of recovery of muscle oxygenation (MO) from comparable levels of exercise in patients with chronic congestive heart failure (CHF) and in normal subjects, and to relate MO kinetics to the level of exercise intolerance. Ten patients with stable CHF secondary to ischemic cardiomyopathy (ejection fraction 34 ± 6%) (mean age 47 ± 10 years) and 8 healthy matched control subjects underwent an upright incremental cycle ergometer exercise test with gas exchange analysis and a 6-minute constant work rate protocol at 60% of peak oxygen consumption (V̇O2). Oxygenation of the vastus lateralis muscle was continuously monitored during exercise and recovery using near infrared spectroscopy. Recovery V̇O2 and MO mean response times for the constant work rate exercise test were longer in patients with CHF than in control subjects (p <0.05). Both V̇O2 and MO mean response times were inversely related to peak VO2 (r = −0.73 and −0.52, respectively; p <0.05 for both). Thus recovery of muscle and total body oxygenation from submaximal exercise is more delayed the greater the cardiac dysfunction, as assessed by peak V̇O2. This suggests that regeneration of phosphocreatine and/or resaturation of venous oxyhemoglobin take place more slowly the worse the cardiac function.

Effect of amlodipine on norepinephrine kinetics and baroreflex function in patients with congestive heart failure

Background: The use of calcium channel blocking drugs is controversial in heart failure, partly because of concerns about neurohormonal stimulation. Preliminary data suggest that the newer agent amlodipine may be useful in this syndrome. Suppression of sympathetic activity either directly or by sensitized baroreflex function could be contributing factors to the clinical use of this drug. Objective: To assess the effect of short-term amlodipine therapy on baseline measures of sympathetic activity and baroreflex function in patients with chronic stable congestive heart failure (CHF). Methods: Seven patients with chronic CHF (New York Heart Association functional class II or III, moderate to severe reduction in left ventricular systolic function) were studied. All patients underwent baroreflex testing with head-up tilt, head-down tilt, and head-down tilt with phenylephrine infusion. Heart rate, mean arterial pressure, forearm blood flow and resistance, and plasma norepinephrine (NE) kinetics were assessed at baseline and after each baroreflex perturbation on three occasions: a control test and after 10 days each of placebo and amlodipine therapy. Results: Plasma NE and NE spillover did not significantly increase after amlodipine administration compared with control and placebo tests (488 ± 119 pg/ml vs 350 ± 85 and 325 ± 87 pg/ml). In three subjects, plasma NE levels were essentially unchanged, whereas in four they rose markedly (289 ± 87 pg/ml at control vs 551 ± 158 pg/ml). There was no difference in the response of any variable during baroreflex perturbations after amlodipine administration compared with control and placebo tests. One subject who tolerated head-down tilt coupled with phenylephrine administration during the control and placebo tests became markedly short of breath during the same intervention after amlodipine administration. Plasma NE levels in this patient had risen markedly while receiving amlodipine and were not appropriately suppressed during the baroreflex loading maneuver. Conclusions: Short-term therapy with amlodipine does not suppress sympathetic activity or alter efferent responses to baroreflex perturbation in patients with stable chronic CHF. Significant increases in plasma NE and NE spillover and abnormal responses to baroreflex stimulation are possible after administration of this drug. The relevance of these findings to studies in larger number of patients requires further study. (Am Heart J 1997;134:13-9.)