Androgen status in non-diabetic elderly men with heart failure.

PURPOSE: We aimed at evaluating androgen status (serum testosterone [TT] and estimated free testosterone [eFT]) and its determinants in non-diabetic elderly men with heart failure (HF). Additionally, we investigated its associations with body composition and long-term survival. METHODS: Seventy three non-diabetic men with HF and 20 healthy men aged over 55 years were studied. Echocardiography, 6-min walk test, grip strength, body composition measurement by DEXA method were performed. TT, sex hormone binding globulin, NT-proBNP, and adipokines (adiponectin and leptin) were measured. All-cause mortality was evaluated at six years of follow-up. RESULTS: Androgen status (TT, eFT) was similar in elderly men with HF compared to healthy controls (4.79 ± 1.65 vs. 4.45 ± 1.68 ng/ml and 0.409 ± 0.277 vs. 0.350 ± 0.204 nmol/l, respectively). In HF patients, TT was positively associated with NT-proBNP (r= 0.371, p = 0.001) and adiponectin levels (r = 0.349, p = 0.002), while inverse association was noted with fat mass (r = -0.413, p < 0.001). TT and eFT were independently determined by age, total fat mass and adiponectin levels in elderly men with HF (p < 0.05 for all). Androgen status was not predictor for all-cause mortality at six years of follow-up. CONCLUSIONS: In non-diabetic men with HF, androgen status is not altered and is not predictive of long-term outcome.

Regional differences among female patients with heart failure from the Cardiac Insufficiency BIsoprolol Study in ELDerly (CIBIS-ELD).

BACKGROUND: The aim of our study was to examine regional differences in the demographics, etiology, risk factors, comorbidities and treatment of female patients with heart failure (HF) in the Cardiac Insufficiency BIsoprolol Study in ELDerly (CIBIS-ELD) clinical trial. METHODS AND RESULTS: One hundred and fifty-nine female patients from Germany and 169 from Southeastern (SE) Europe (Serbia, Slovenia and Montenegro) were included in this subanalysis of the CIBIS-ELD trial. Women comprised 54% of the study population in Germany and 29% in SE Europe. German patients were significantly older. The leading cause of HF was arterial hypertension in German patients, 71.7% of whom had a preserved ejection fraction. The leading etiology in SE Europe was the coronary artery disease; 67.6% of these patients had a reduced left ventricular ejection fraction (34.64 ± 7.75%). No significant differences were found in the prevalence of traditional cardiovascular risk factors between the two regions (hypertension, diabetes, hypercholesterolemia, smoking and family history of myocardial infarction). Depression, chronic obstructive pulmonary disease and malignancies were the comorbidities that were noted more frequently in the German patients, while the patients from SE Europe had a lower glomerular filtration rate. Compared with the German HF patients, the females in SE Europe received significantly more angiotensin converting enzyme inhibitors, loop diuretics and less frequently angiotensin receptor blockers and mineralocorticoid receptor antagonists. CONCLUSIONS: Significant regional differences were noted in the etiology, comorbidities and treatment of female patients with HF despite similar risk factors. Such differences should be considered in the design and implementation of future clinical trials, especially as women remain underrepresented in large trial populations.

Rapidly vanishing lung pseudotumor in a patient with acute bilateral bronchopneumonia.

INTRODUCTION: Rapidly vanishing lung pseudotumor (phantom tumor) refers to the transient well-demarcated accumulation of pleural fluid in the interlobar pulmonary fissures. Most frequently their appearance is associated with congestive heart failure, but also other disorders like hypoalbuminemia, renal insufficiency or pleuritis. Its rapid disappearance in response to the treatment of the underlying disorder is a classical feature of this clinical entity. CASE REPORT: A 47-year-old woman, chronic smoker with symptoms of shortness of breath, orthopnea, chills, cough, weakness and the temperature of 39.2 degrees C was admitted to our hospital. A posteroanterior chest X-ray revealed cardiomegaly with the cardiothoracic ratio of > 0.5, blunting of both costophrenic angles and an adjacent 6 x 5 cm well-defined, rounded opacity in the right interlobar fissure. Transthoracic 2-dimensional echocardiography demonstrated left ventricular hyperthrophy with a systolic ejection fraction of 25% and moderate mitral regurgitation. The patient's symptoms resolved rapidly after diuresis, and repeated chest X-ray four days later showed that the right lung opacity and pleural effusions had vanished. CONCLUSION: The presented case underlines the importance of the possibility of vanishing lung tumor in patients with left ventricular failure and a sharp oval lung mass on the chest X-ray. This is the way to avoid incorrect interpretation of this finding causing additional, unnecessary, costly or invasive imaging, interventions and drugs.

Effect of myocardial revascularisation on left ventricular systolic function in patients with and without viable myocardium: should non-viable segments be revascularised?

OBJECTIVE: To assess the effect of surgical revascularisation on left ventricular (LV) systolic function in patients with viable and non-viable dysfunctional LV segments determined by low dose dobutamine stress echocardiography (DSE). DESIGN: Prospective observational cohort study. SETTING: Single tertiary care centre. PATIENTS: Consecutive patients referred to surgical revascularisation (n=115). INTERVENTIONS: DSE and surgical revascularisation. MAIN OUTCOME MEASURES: Functional recovery defined as increase in ejection fraction ≥ 5% 1 year after revascularisation in patients with and without viable myocardium (viability defined as improvement of contractility in ≥ 4 LV segments on DSE). RESULTS: The mean age, ejection fraction and wall motion score index (WMSi) of patients were 59 ± 9 years, 44 ± 9% and 1.82 ± 0.31, respectively. There was no difference between DSE positive and DSE negative patients for any of those parameters at baseline study (p>0.05 for all). After 12 months, the ejection fraction increased 11 ± 1% in patients with viable myocardium vs 7 ± 1% in patients without viable myocardium (p=0.002). Moreover, in patients with viable myocardium, the greatest increase of ejection fraction occurred 1 month after surgery (9 ± 1%), whereas in those patients with negative DSE the ejection fraction increased more gradually (2±1% after 1 month, p=0.002 between groups for 1 month vs preoperative value), but still improved after 12 months follow-up (p<0.0001 in time for both groups). CONCLUSIONS: It appears that patients with LV dysfunction, but without viable myocardium, may also benefit from myocardial revascularisation. Functional recovery continuously occurs throughout the first year after surgical treatment.

The absence of the ST-segment elevation in acute coronary artery thrombosis: what does not fit, the patient or the explanation?

In a few patients with acute proximal thrombotic occlusion of the left anterior descending coronary artery (LAD), tall ischemic T waves never evolve into ST-segment elevation. This was recently inaccurately reported as a "novel sign" of proximal LAD occlusion. It has been speculated that the absence of ST-segment elevation could be attributed to the large area of transmural ischemia, the anatomic variant of Purkinje fibers, or to lack of activation of sarcolemal adenosine triphosphate-potassium channels. This electrocardiographic picture was recently explained by changes in the subendocardial but not in the epicardial action potential, suggesting subendocardial ischemia as the underlying mechanism. We present a patient with thrombotic lesion of proximal LAD, static precordial ST-segment depression, and tall T waves who underwent primary percutaneous intervention and stent placement. Surprisingly, total thrombotic stent occlusion on the following day was associated with ST-segment elevation in precordial leads, indeed supporting the concept of the regional subendocardial ischemia that was first described more than a decade ago.

Relationship between RANKL and neuroendocrine activation in elderly males with heart failure.

The main cytokines regulating bone remodeling are the receptor activator of nuclear factor-κB ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG). Recent data have linked RANKL and OPG to cardiovascular disease as well. NT-pro-BNP and adiponectin are well-established biomarkers of heart failure reflecting neuroendocrine activation in this multi-complex disorder. The objective of this article was to investigate whether RANKL is associated with neuroendocrine activation in 75 elderly males with mild to moderate congestive heart failure (CHF) and left ventricular ejection fraction <40%. The control group consisted of 20 healthy male volunteers with matching age and body mass index (BMI). Serum RANKL (sRANKL), OPG, NT-pro-BNP, adiponectin, leptin, clinical, and echocardiography parameters were evaluated. In comparison to the control group, the CHF patients showed significantly increased sRANKL levels [126.8 (122.6) vs. 47.8 (44.4) pg/ml, P < 0.0001]. There was a significant relative risk of systolic CHF in elderly males associated with increased sRANKL above the calculated cut-off of 83 pg/ml [OR = 10.286 (95%CI 3.079-34.356), P < 0.0001; RR = 3.600 (95%CI = 1.482-8.747)]. In the CHF patients, the log-transformed values of sRANKL levels correlated positively with the log-transformed values of the serum NT-pro-BNP and adiponectin levels (P = 0.004, r = 0.326 and P = 0.037, r = 0. 241, respectively), while inversely correlated with the BMI and creatinine clearance (P = 0.015, r = -0.281 and P = 0.042, r = -0.236, respectively). In multivariate regression model, sRANKL was a significant determinant of NT-pro-BNP independent of age, BMI and creatinine clearance (P = 0.002, R (2) = 0.546). In conclusion, our study suggests that in elderly males with systolic heart failure sRANKL was significantly associated with parameters of neuroendocrine activation such as NT-pro-BNP and adiponectin. Further studies are needed to elucidate the potential role of sRANKL in the complex pathogenesis of heart failure.

Primary PCI for acute myocardial infarction in a patient with idiopathic thrombocytopenic purpura. A case report and review of the literature.

BACKGROUND AND PURPOSE: The occurrence of acute myocardial infarction (AMI) in patients with idiopathic thrombocytopenic purpura (ITP) is rare, especially when the platelet count is low. Since only few case reports have been published, there are no recommendations for the management of thrombocytopenic patients with AMI. The aim of the present study is to discuss different aspects of this challenging issue and to review limited data available in the literature. CASE STUDY: An 80-year-old patient with ITP (platelet count 5 . 10(9)/l) is presented who developed an AMI (ST segment elevation myocardial infarction) and was successfully treated by primary percutaneous coronary intervention (PCI). CONCLUSION: Considering the high bleeding risk in patients with ITP and AMI, careful balance between usual anticoagulation and antiplatelet therapy on the one hand, and efforts to raise platelet count on the other hand are needed.

Hypothetical mechanism of sodium pump regulation by estradiol under primary hypertension.

Causal relationship between sodium and hypertension has been proposed and various changes in Na+,K+-ATPase (sodium pump) activity have been described in established primary hypertension. A number of direct vascular effects of estradiol have been reported, including its impact on the regulation of sodium pump activity and vasomotor tone. The effects of estradiol involve the activation of multiple signaling cascades, including phosphatydil inositol-3 kinase (PI3K) and p42/44 mitogen-activated protein kinase (p42/44(MAPK)). In addition, some of the effects of estradiol have been linked to activity of cytosolic phospholipase A(2) (cPLA(2)). One possible cardioprotective mechanism of estradiol involves of the interaction between estradiol and the rennin-angiotensin system (RAS). Elevated circulating and tissue levels of angiotensin II (Ang II) have been implicated in the development of hypertension and heart failure. The aim of our investigation was to elucidate the signaling mechanisms employed by estradiol and Ang II in mediating sodium pump, in vascular smooth muscle cells (VSMC). The aim of our investigation was to elucidate the signaling mechanisms employed by estradiol and Ang II in mediating sodium pump activity/expression in VSMC, with particular emphasis on PI3K/cPLA(2)/p42/44(MAPK) signaling pathways. Our primary hypothesis is that estradiol stimulates sodium pump activity/expression in VSMC via PI3K/cPLA(2)/p42/44(MAPK) dependent mechanism and, that impaired estradiol-stimulated sodium pump activity/expression in hypertensive rodent models (i.e. SHR), Ang II-mediated vascular impairment of estradiol is related to a decrease ability of estradiol to stimulate the PI3K/cPLA(2)/p42/44(MAPK) signaling pathways. An important corollary to this hypothesis is that in hypertensive state (i.e. SHR rats) the decreasing in ACE enzyme activity and/or AT1 receptor expression caused by administration of estradiol is accompanying with abrogated ability of Ang II to decrease IRS-1/PI3K association, and consequent PI3K/cPLA(2)/p42/44(MAPK) activity and associated sodium pump activity/expression. A clear characterization of how Ang II attenuates estradiol signaling may lead to a better understanding of the molecular mechanism(s) underlying pathophysiological conditions such as hypertension and to understanding how certain pathophysiological situations affect sodium pump activity/expression in VSMC.

Regulation of the inducible nitric oxide synthase and sodium pump in type 1 diabetes.

Insulin-like growth factor-1 (IGF-1) is a hormone and growth factor closely related to insulin. The autocrine/paracrine actions of IGF-1 involve activation of inducible nitric oxide synthase (iNOS) and the Na(+), K(+)-ATPase sodium pump in cardiovascular tissues. Data from literature indicate that iNOS is expressed in vascular smooth muscle cells (VSMC) and that IGF-1-induced release of NO is both rapid and delayed. We hypothesize that impaired IGF-1-induced sodium pump activity/expression in rats with type 1 diabetes is related to activation of phosphatidylinositol 3 kinase (PI3K)/cytosolic phospholipase 2 (cPLA(2))/protein kinase B (Akt) signaling, and that IGF-1 prevents acute and chronic dysfunction of iNOS and sodium pump activity in a chemically induced model of type 1 diabetes, the streptozotocin-treated rat heart (STZ). Understanding how iNOS and sodium pump activity are regulated by IGF-1 activation of the PI3K/cPLA(2)/Akt cascade should provide novel and fundamental knowledge regarding the regulatory actions of IGF-1 in promoting vasodilation. Since insulin resistance is currently a major focus of research, the use of IGF-1 to improve insulin resistance and glucose metabolism has opened a new arena for treatment of comorbid conditions. Future investigations should now focus on mechanisms of action of IGF-1 and its clinical applicability.