The reliability of a clinical diagnosis of heart failure in primary care is poor. Concentrations of natriuretic peptides are high in heart failure. This population-based study examined the predictive ...value of natriuretic peptides in patients with a new primary-care diagnosis of heart failure.
Concentrations of plasma atrial (ANP and N-terminal ANP) and B-type (BNP) natriuretic peptides were measured by radioimmunoassay in 122 consecutive patients referred to a rapid-access heart-failure clinic with a new primary-care diagnosis of heart failure. On the basis of clinical assessment, chest radiography, and transthoracic echocardiography, a panel of three cardiologists decided that 35 (29%) patients met the case definition for new heart failure. ANP and NT-ANP results were available for 117 patients (34 with heart failure) and BNP results for 106 (29 with heart failure).
Geometric mean concentrations of natriuretic peptides were much higher in patients with heart failure than in those with other diagnoses (29.2
vs 12.4 pmol/L for ANP; 63.9
vs 13.9 pmol/L for BNP; 1187
vs 410.6 pmol/L for NT-ANP; all p<0.001). At cut-off values chosen to give negative predictive values for heart failure of 98% (ANP ≥18.1 pmol/L, NT-ANP ≥537.6 pmol/L, BNP ≥22.2 pmol/L), the sensitivity, specificity, and positive predictive value for ANP were 97%, 72%, and 55%; for NT-ANP 97%, 66%, and 54%; and for BNP 97%, 84%, and 70%. Addition of ANP or NT-ANP concentration or both did not improve the predictive power of a logistic regression model containing BNP concentration alone.
In patients with symptoms suspected by a general practitioner to be due to heart failure, plasma BNP concentration seems to be a useful indicator of which patients are likely to have heart failure and require further clinical assessment.
Some studies have suggested that treatment with recombinant human growth hormone (rhGH) increases left-ventricular mass and improves haemodynamic and functional status in patients with heart failure ...due to dilated cardiomyopathy. We did a double-blind, randomised, placebo-controlled study of rhGH in patients with chronic heart failure due to dilated cardiomyopathy.
50 patients (43 men) were randomly allocated treatment with subcutaneous rhGH (2 IU daily) or placebo for a minimum of 12 weeks. The primary endpoints were the effects on left-ventricular mass and systolic wall stress. The secondary endpoints were the effects on left-ventricular size and function. Data were analysed by intention to treat.
Patients in the rhGH group had an increase in left-ventricular mass compared with those in the placebo group (27%, p=0·0001). There was no significant difference in left-ventricular systolic wall stress, mean blood pressure, or systemic vascular resistance between the two groups. New York Heart Association functional class, left-ventricular ejection fraction, and distance on the 6 min walking test were unchanged. The change in serum insulin-like growth factor (IGF)-I concentrations (rhGH 77 ng/mL; placebo -19 ng/mL, GH vs placebo p=0·0001) was significantly related to the change in left-ventricular mass (r=0·55, p=0·0001). One patient in the rhGH group was withdrawn at 6 weeks because of worsening heart failure.
There is a significant increase in left-ventricular mass in patients with dilated cardiomyopathy given rhGH but this is not accompanied by an improvement in clinical status. Changes in left-ventricular mass are related to changes in serum IGF-I concentrations. Whether a longer treatment period would provide clinical benefits and decrease mortality is unknown.
Although some patients with adult congenital heart disease (ACHD) report limitations in exercise capacity, we hypothesized that depressed exercise capacity may be more widespread than superficially ...evident during clinical consultation and could be a means of assessing risk.
Cardiopulmonary exercise testing was performed in 335 consecutive ACHD patients (age, 33+/-13 years), 40 non-congenital heart failure patients (age, 58+/-15 years), and 11 young (age, 29+/-5 years) and 12 older (age, 59+/-9 years) healthy subjects. Peak oxygen consumption (peak VO2) was reduced in ACHD patients compared with healthy subjects of similar age (21.7+/-8.5 versus 45.1+/-8.6; P<0.001). No significant difference in peak VO2 was found between ACHD and heart failure patients of corresponding NYHA class (P=NS for each NYHA class). Within ACHD subgroups, peak VO2 gradually declined from aortic coarctation (28.7+/-10.4) to Eisenmenger (11.5+/-3.6) patients (P<0.001). Multivariable correlates of peak VO2 were peak heart rate (r=0.33), forced expiratory volume (r=0.33), pulmonary hypertension (r=-0.26), gender (r=-0.23), and body mass index (r=-0.19). After a median follow-up of 10 months, 62 patients (18.5%) were hospitalized or had died. On multivariable Cox analysis, peak VO2 predicted hospitalization or death (hazard ratio, 0.937; P=0.01) and was related to the frequency and duration of hospitalization (P=0.01 for each).
Exercise capacity is depressed in ACHD patients (even in allegedly asymptomatic patients) on a par with chronic heart failure subjects. Lack of heart rate response to exercise, pulmonary arterial hypertension, and impaired pulmonary function are important correlates of exercise capacity, as is underlying cardiac anatomy. Poor exercise capacity identifies ACHD patients at risk for hospitalization or death.
Oscillatory breathing patterns characterized by rises and falls in ventilation with apnea (Cheyne-Stokes respiration CSR) or without apnea (periodic breathing PB) commonly occur during the daytime in ...chronic heart failure (CHF). We have prospectively characterized patients with cyclical breathing in terms of clinical characteristics, indices of autonomic control, prognosis, and the role of peripheral chemosensitivity.
To determine cyclical breathing pattern, power spectral analysis was applied to 30-minute recordings of respiration in 74 stable CHF patients. Analyses of heart rate variability and baroreflex sensitivity were used to assess autonomic balance. Peripheral chemosensitivity was assessed with the transient hypoxia method. We also determined whether the suppression of peripheral chemoreceptor activity (hyperoxia or dihydrocodeine) would influence the respiratory pattern. Cyclical respiration was found in 49 (66%) patients (22 30% CSR, 27 36% PB) and was associated with more advanced CHF symptoms, impaired autonomic balance, and increased chemosensitivity (0.80 and 0.75 versus 0.34 L. min(-1). %SaO(2)(-1), P<0.001, for CSR and PB versus normal breathing, respectively). Transient hyperoxia abolished oscillatory breathing in 7 of 8 patients. Dihydrocodeine administration decreased chemosensitivity by 42% (P=0.05), which correlated with improvement in respiratory pattern. Cyclical breathing predicted poor 2-year survival (relative risk 9.41, P<0.01, by Cox proportional hazards analysis), independent of peak oxygen consumption (P=0.04).
An oscillatory breathing pattern during the daytime is a marker of impaired autonomic regulation and poor outcome. Augmented activity of peripheral chemoreceptors may be involved in the genesis of this respiratory pattern. Modulation of peripheral chemosensitivity can reduce or abolish abnormal respiratory patterns and may be an option in the management of CHF patients with oscillatory breathing.
Until menopause, women appear to be protected from coronary heart disease. Evidence suggests that estrogen may play a role in the protection of the cardiovascular system by exerting a beneficial ...effect on risk factors such as cholesterol metabolism and by a direct effect on the coronary arteries. To date there has been no evidence linking testosterone with the occurrence of coronary heart disease. Testosterone may affect the cardiovascular system directly, thus partially explaining the difference in the incidence of coronary artery disease in men and premenopausal women. The purpose of this study was to assess the direct effect of testosterone and a number of testosterone analogues on rabbit coronary arteries and aorta in vitro.
Rings of coronary artery and aorta of adult male or nonpregnant female New Zealand White rabbits were suspended in organ baths containing Krebs solution; isometric tension then was measured. The response to testosterone was investigated in prostaglandin F2 alpha (PGF 2 alpha)- and KCl-contracted rings. The effects of endothelium and nitric oxide synthase, prostaglandin synthetase, and guanylate cyclase inhibition on testosterone-induced relaxation were investigated. The effects of ATP-sensitive potassium channels and potassium conductance were also assessed. Relaxing responses in the presence of aromatase inhibition and testosterone receptor blockade were performed. The relaxing responses to the testosterone analogues etiocholan-3 beta-ol-17-one, epiandrosterone, 17 beta-hydroxy-5 alpha-androst-1-en-3-one, androst-16-en-3-ol, and testosterone enanthanate were measured. Testosterone relaxed rabbit coronary arteries and aorta. There was no significant difference between the relaxation effect of testosterone with or without endothelium. Similar results were obtained from male and nonpregnant female rabbits. The relaxing response of testosterone in the coronary artery was significantly greater than in the aorta. The relaxing response of testosterone in the coronary artery was significantly reduced by the potassium channel inhibitor barium chloride but not by the ATP-sensitive potassium channel inhibitor glibenclamide. The relaxing response to testosterone was greater in PGF 2 alpha-contracted rings compared with KCl-contracted rings. Inhibitors of nitric oxide synthase, prostaglandin synthetase, and guanylate cyclase did not affect relaxation induced by testosterone. Inhibition of aromatase and testosterone receptors did not affect relaxation. Testosterone did not shift the rabbit coronary arterial calcium concentration-dependent contraction curves, whereas verapamil did. There were, however, significant differences in the relaxing response to testosterone compared with testosterone analogues. Testosterone was the most potent relaxing agent, suggesting that there may be a structure-function relation in the relaxing response.
Testosterone induces endothelium-independent relaxation in isolated rabbit coronary artery and aorta, which is neither mediated by prostaglandin I2 or cyclic GMP. Potassium conductance and potassium channels but not ATP-sensitive potassium channels may be involved partially in the mechanism of testosterone-induced relaxation. The in vitro relaxation is independent of sex and of a classic receptor. The coronary artery is significantly more sensitive to relaxation by testosterone than the aorta. Testosterone is a more potent relaxing agent of rabbit coronary artery than other testosterone analogues.
Gap junctions are a determinant of myocardial conduction. Disturbances of gap-junctional content may account for abnormalities of impulse propagation, contributing to the arrhythmic tendency and ...mechanical inefficiency of ischemic and hypertrophied myocardium. The aim of this study was to characterize gap junction organization in normal human ventricular myocardium and to establish whether abnormalities exist in myocardium of chronically ischemic and hypertrophied hearts.
Cardiac gap-junctional connexin43 antibodies and confocal microscopy were used in a quantitative immunohistochemical study of surgical myocardial samples to explore the structural basis of electromechanical ventricular dysfunction in chronic ischemic and hypertrophic heart diseases. Normal adult human left ventricular myocardium had a gap-junctional surface area of 0.0051 micron2/micron3 myocyte volume; gap junctions were confined to intercalated disks, of which there was a mean of 11.6 per cell. The right ventricle showed similar gap junction surface area. Left ventricular myocardium from ischemic hearts (distant from any fibrotic scarring), despite normal numbers of intercalated disks per cell, had a reduced gap junction surface area (0.0027 micron2/micron3; P = .02), as did hypertrophied myocardium (0.0031 micron2/micron3; P = .05). The cardiac myocytes in the pathological tissues were larger than normal, and estimated gap-junctional content per cell was reduced in ischemic ventricle (P = .02) compared with normal.
Gap junctions in normal adult human working ventricular myocardium occupy an area of 0.0051 micron2/micron3 myocyte volume. This surface area is reduced in ventricular myocardium from hearts subject to chronic hypertrophy and ischemia, despite a normal number of intercellular abutments, and this alteration may contribute to abnormal impulse propagation in these hearts.
Background. Recent studies of growth hormone supplementation in chronic heart failure have been associated with variable results. Acquired abnormalities of biochemical parameters of the growth ...hormone insulin-like growth factor I axis have been associated with severe chronic heart failure. There are suggestions of an acquired growth hormone resistance with deficient insulin-like growth factor I in some patients.
Objectives. Therefore, we set out to investigate the clinical and functional status and the degree of cytokine and neurohormonal alteration of chronic heart failure patients with deficient insulin-like growth factor I responses.
Methods. Patients with chronic heart failure were divided into two groups according to their insulin-like growth factor I levels (classified according to the manufacturer’s assay range in normal controls): low insulin-like growth factor I <104 (n = 20; 89 ± 9.6 ng/ml), and normal/high >104 ng/ml (n = 32; 169 ± 52 ng/ml). Between groups there was no difference in age (low versus high: 65.3 ± 12.1 versus 61.6 ± 9.1 years, p = 0.21), body mass index, aerobic capacity (peak oxygen consumption: low versus high: 15.5 ± 5.2 versus 17.3 ± 6.3 mL/kg/min, p = 0.23), left ventricular ejection fraction, New York Heart Association classification.
Results. During quadriceps strength testing, patients with low insulin-like growth factor I had reduced absolute strength (−24%), and strength per unit area muscle (−14%) than patients with normal/high insulin-like growth factor I. Leg muscle cross-sectional area was lower in the low insulin-like growth factor I group (−12% and −13% for right and left legs, respectively). These alterations were accompanied by increased levels of growth hormone (+145%), tumor necrosis factor-alpha (+46%), cortisol/dehydroepiandrosterone ratio (+60%), noradrenaline (+49%) and adrenaline (+136%) (all at least p < 0.05).
Conclusions. Patients with low insulin-like growth factor I levels show signs of altered body composition, cytokine and neuroendocrine activation, to a greater extent than patients with normal/high levels.
Cardiac amyloidosis can be diagnostically challenging. Cardiovascular magnetic resonance (CMR) can assess abnormal myocardial interstitium.
Late gadolinium enhancement CMR was performed in 30 ...patients with cardiac amyloidosis. In 22 of these, myocardial gadolinium kinetics with T1 mapping was compared with that in 16 hypertensive controls. One patient had CMR and autopsy only. Subendocardial T1 in amyloid patients was shorter than in controls (at 4 minutes: 427+/-73 versus 579+/-75 ms; P<0.01), was shorter than subepicardium T1 for the first 8 minutes (P< or =0.01), and was correlated with markers of increased myocardial amyloid load, as follows: left ventricular (LV) mass (r=-0.51, P=0.013); wall thickness (r=-0.54 to -0.63, P<0.04); interatrial septal thickness (r=-0.52, P=0.001); and diastolic function (r=-0.42, P=0.025). Global subendocardial late gadolinium enhancement was found in 20 amyloid patients (69%); these patients had greater LV mass (126+/-30 versus 93+/-25 g/m2; P=0.009) than unenhanced patients. Histological quantification showed substantial interstitial expansion with amyloid (30.5%) but only minor fibrosis (1.3%). Amyloid was dominantly subendocardial (42%) compared with midwall (29%) and subepicardium (18%). There was 97% concordance in diagnosis of cardiac amyloid by combining the presence of late gadolinium enhancement and an optimized T1 threshold (191 ms at 4 minutes) between myocardium and blood.
In cardiac amyloidosis, CMR shows a characteristic pattern of global subendocardial late enhancement coupled with abnormal myocardial and blood-pool gadolinium kinetics. The findings agree with the transmural histological distribution of amyloid protein and the cardiac amyloid load and may prove to have value in diagnosis and treatment follow-up.
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