There is evidence that natriuretic peptide (namely atrial and/or B-type natriuretic peptides) plasma concentration may be elevated in many clinical conditions besides cardiovascular diseases, the ...most frequent being lung diseases, renal and liver failure, acute cerebrovascular events, acute and chronic inflammatory diseases and certain metabolic and endocrine disorders. In general, increased circulating levels of natriuretic peptides (compared to the normal range of a healthy population) may be considered expression of activation of the neuro-endocrine system, which can be the cause or consequence of cardiac stressor events. Furthermore, some variables, such as gender and obesity, may affect natriuretic peptide secretion and plasma concentration by completely extra-cardiac mechanisms. Increased expression of the natriuretic peptide system, counteracting neuro-hormonal and immunological activation, may occur in many clinical conditions, as witnessed by the considerable number of diseases in which the natriuretic peptide system has been found to be altered. Several studies have demonstrated that higher circulating levels of natriuretic peptides represent a strong independent risk factor for major cardiovascular complications and/or death, even in extra-cardiac diseases. Because several of these diseases may be present in patients with left ventricular dysfunction, the possible influence on diagnostic and prognostic accuracy of natriuretic peptides in heart failure will be discussed. Clin Chem Lab Med 2008;46:1515–23.
Atrial and brain natriuretic peptides (ANP and BNP) plasma concentration increases and holds a prognostic significance in patients with left ventricular dysfunction. We assessed the hypothesis that ...right ventricular (RV) overload might significantly contribute to plasma elevation of cardiac natriuretic hormones in patients with heart failure.
Forty-one patients with cardiomyopathy and depressed left ventricular (LV) function (ejection fraction, EF, <40%), underwent cardiac magnetic resonance imaging (MRI) and resting plasma determination of ANP and BNP. Nineteen healthy subjects were also studied as control group. Ventricular volumes and function were assessed by MRI.
In the group of patients, LVEF was 22.6±1.2% (controls: 61.2±1.3%,
P<0.001, mean±S.E.M.), while RVEF was 48.2±2.5% (controls: 66.7±1.6%,
P<0.001); LV and RV end diastolic/systolic volumes, corrected by body surface area, were 143±7/114±7 ml/m
2 (controls 70±3/27±2 ml/m
2, both
P<0.001) and 66±3/37±4 ml/m
2 (controls: 63±4/21±2 ml/m
2,
P<0.01 only for end-systolic volume). BNP plasma value was on average 324±39 pg/ml (range: 23–1280, controls 10±2 pg/ml), ANP value was 144±17 pg/ml (range: 26–534, controls 15±1 pg/ml). BNP positively correlated with either end-diastolic or end-systolic RV volume in patients, less with LV systolic, and not with LV diastolic volume.
Moreover, a significant negative correlation was observed between BNP and either LVEF or RVEF. Conversely, ANP showed a significant correlation only with end-systolic RV volume and with both RVEF and LVEF. When multivariate stepwise linear regression analysis was applied LVEF resulted the only independent predictor for ANP plasma values (
R=0.591,
P<0.001), while LVEF and RV end-diastolic volume for BNP (
R=0.881,
P<0.001, and
R=0.881,
P=0.035, respectively).
Right heart overload contributes independently to plasma elevation of natriuretic peptides. RV involvement, which is known to independently worsen prognosis in patients with cardiomyopathy, might contribute to their established prognostic power, inducing compensatory secretion of plasma cardiac natriuretic hormones.
Background: An increased risk for life-threatening arrhythmias and sudden death has been observed in hypertensive patients, associated with either left ventricular hypertrophy (LVH) or prolonged QT ...interval. To investigate the influence of autonomic imbalance and LVH on QT interval in hypertensive patients, we compared two different models of LVH: hypertension and endurance physical training.
Methods: Forty-seven untreated subjects affected by essential hypertension and 35 endurance runners, with a similar degree of LVH, were enrolled into the study. All subjects underwent 24-h ambulatory ECG recording and morning blood sampling for catecholamines. Heart rate variability was evaluated by spectral analysis and a computerized algorithm was used to measure the QT interval; QTc was then computed by the Bazett's formula. Left ventricular mass index (LVMI) was assessed by echocardiogram.
Results: No difference in LVMI was found between hypertensive patients and athletes. Athletes showed lower heart rate (64±1 vs. 75±1 bpm,
p<0.001, mean±S.E.M.) and shorter QTc (401±3 vs. 434±4 ms,
p<0.001) than hypertensive patients throughout the 24-h period. Athletes showed a higher vagal drive compared to hypertensive patients as suggested by bradycardia and higher values of vagal indices, which negatively correlated with QTc. Plasma norepinephrine was significantly lower in athletes than in hypertensive patients (
p<0.05) and positively correlated with QTc.
Conclusion: Despite similar degrees of LVH, hypertensive patients show QTc lengthening, as compared to athletes. Heart rate variability and plasma norepinephrine levels suggest sympathetic predominance in hypertensive patients, which could contribute to abnormal ventricular repolarization, thus identifying patients with an increased arrhythmic risk.
Natriuretic peptide testing in primary care patients Emdin, Michele; Fontana, Marianna; Poletti, Roberta ...
Clinical chemistry and laboratory medicine,
11/2008, Letnik:
46, Številka:
11
Journal Article, Conference Proceeding
Recenzirano
The evaluation of cardiac endocrine function by means of automated robust assays has permitted the introduction of a cheap and powerful clinical tool. Plasma concentration of B-type-related ...natriuretic peptides is a marker of either hemodynamic or neurohormonal stress on the heart and has been validated within the diagnostic and prognostic domain in patients with suspected or ascertained heart failure, mostly in the in-hospital setting. Evidence is growing, supporting an out-of-hospital use, namely in primary care. Its implementation in this setting in screening programs and diagnostic algorithms might contribute to decrease the apparent disparity between the general practitioner and the specialist approach to disease management. Clin Chem Lab Med 2008;46:1533–42.
The search for the presence of Cheyne-Stokes respiration should be introduced into the routine diagnostic process in heart failure patients, owing to its clinical and prognostic implications. The ...analysis of this specific alteration of the respiratory pattern could contribute both to the understanding of its pathophysiological role, and to the discovery of specific treatments for heart failure patients, characterized by poor prognosis, despite optimal conventional treatment.
Aim Systemic sclerosis (SSc) may be associated with right ventricular overload, secondary to pulmonary hypertension. In heart failure patients, neuroendocrine derangements can influence clinical ...evolution and prognosis. The aim of this study was to investigate neurohormonal control affected in SSc patients with and without right ventricular impairment. Methods and results A prospective series of 28 patients with SSc was studied. In addition to conventional evaluations, extensive neuroendocrine studies were done, including assays of both the vasoconstrictor system (plasma renin activity PRA, aldosterone and catecholamines) and vasodilatory molecules (brain natriuretic peptide BNP and atrial natriuretic peptide ANP). A significant relation was observed between echo-Doppler estimated pulmonary systolic pressure (PAP) and neurohormonal activation, in particular between PAP and BNP (R=0.58, p=0.004), ANP (R=0.65, p<0.001) and PRA (R=0.45, p=0.032). Patients with right ventricular overload (i.e., PAP>40 mmHg confirmed at cardiac catheterization) had higher levels of ANP and BNP (147±26 vs 34±6 pg/mL and 344±86 vs 30±7 pg/mL, respectively, p<0.001), PRA (6.4±1.9 vs 1.8±0.4 ng/mL/h, p<0.001) and aldosterone (257±86 vs 114±22 pg/mL, p=0.02). These patients had increased plasma noradrenaline, but not adrenaline (701±87 vs 452±66 pg/mL, p<0.001). Conclusion SSc patients with right heart failure have a neurohormonal derangement, showing overactivity of the vasoconstrictive system, counteracted by oversecretion of cardiac natriuretic hormones.
Currently adopted diagnostic flow charts consider transthyretin and light-chain cardiac amyloidosis as mutually exclusive. Here, we report for the first time, to our knowledge, the demonstration of a ...biopsy-proven dual pathology in an 80-year-old man with sequential development of both wild-type transthyretin amyloidosis and light-chain cardiac amyloidosis cardiomyopathy over a 3-year timespan. (Level of Difficulty: Intermediate.).
To characterize the complex picture of neurohormonal abnormalities in heart failure (HF), a comprehensive characterization was prospectively performed in 105 patients with cardiomyopathy at different ...clinical stages and compared to 47 sex/age-matched control healthy subjects. To assess the relationship between the diagnosis of HF and clinical and neurohumoral variables, multiple logistic regression with forward stepwise selection (Wald) was used. The diseased condition was predicted by creatinine level, gamma-glutamyl transpeptidase (GGT) activity, TNF-alpha, and plasma levels of several neurohormonal indices: (a) plasma renin activity; angiotensin II; aldosterone; (b) cortisol as a stress marker; (c) norepinephrine levels; (d) triiodothyronine; (e) ANP and BNP. Thus, renal and hepatic dysfunction, overexpression of cardiac natriuretic hormones, of adrenergic and renin–angiotensin–aldosterone system significantly augment the probability of HF, which was decreased by increasing values of thyroid hormone. In conclusion, a complex neurohormonal derangement associated with an overall predominance of vasoconstrictor systems is characteristic of HF syndrome.
Dans le but de mieux préciser le cadre complexe des perturbations neurohormonales dans la décompensation cardiaque, une ample caractérisation a été menée, de façon prospective, sur 105 patients ayant une cardiomyopathie avec différents degrés de sévérité comparés à 47 sujets sains, appariés pour le sexe et l’âge. La relation entre le diagnostic de décompensation cardiaque et les variables neurohumorales a été évaluée par regression logistique multiple avec test séquentiel de Wald. Le niveau de créatinine, l’activité de la gamma-glutamyl transpeptidase (GGT), le TNFa ainsi que les niveaux plasmatiques de plusieurs signes neurohormonaux tels que (a) l’activité de la rénine plasmatique, de l’angiotensine II, de l’aldostérone, (b) le cortisol en tant que marqueur de stress, (c) les niveaux de norépinéphrine, (d) la triiodothyronine (T3), (e) l’ANP et le BNP ont été mesurés pour leur valeur predictive de la maladie cardiaque. Il en résulte que le dysfonctionnement rénal et hépatique, la surproduction d’hormones natriurétiques cardiaques, et le système rénine–angiotensine–aldostérone augmentent de façon significative la probabilité d’une décompensation cardiaque qui avait été affaiblie par des valeurs plus élevées de T3. En conclusion, le syndrome de la décompensation cardiaque présente une perturbation neurohormonale complexe qui entraîne une prédominance générale des systèmes vasoconstricteurs.
The precise molecular mechanisms that coordinate apoptosis and autophagy in cancer remain to be determined. Here, we provide evidence that the tumor suppressor promyelocytic leukemia protein (PML) ...controls autophagosome formation at mitochondria-associated membranes (MAMs) and, thus, autophagy induction. Our in vitro and in vivo results demonstrate how PML functions as a repressor of autophagy. PML loss promotes tumor development, providing a growth advantage to tumor cells that use autophagy as a cell survival strategy during stress conditions. These findings demonstrate that autophagy inhibition could be paired with a chemotherapeutic agent to develop anticancer strategies for tumors that present PML downregulation.
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•PML regulates autophagic processes from ER/MAM domains in a Ca2+-dependent manner•Localization of PML away from the MAMs is dependent on p53•Activation of autophagy by PML depletion promotes survival under stress conditions•Block of autophagy restores the activity of chemotherapy in PML-downregulated tumors
Missiroli et al. demonstrate that the tumor suppressor promyelocytic leukemia protein (PML) works as a repressor of autophagy by controlling autophagosome formation at mitochondria-associated membranes (MAMs) in a p53-dependent manner. Together, their studies generate alternative anticancer strategies for tumors that present PML downregulation.
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