Cardiogenic shock in cancer

Cardiogenic shock (CS) is increasingly recognized in patients with malignancies, while cancer is independently associated with worse prognosis in CS. A number of conditions may lead to CS in cancer, including acute coronary syndromes, cardiomyopathy, takotsubo syndrome, myocarditis, pulmonary embolism, tamponade, and cardiac herniation. In these conditions, CS may be related to cancer itself or to cancer therapy, including surgery, chemotherapy, or radiotherapy. Given the significantly improved overall survival of patients with malignancies, the early recognition and proper management of CS in cancer become increasingly important. In the present paper, we review the available evidence on CS in patients with malignancies and highlight issues related to its management. © 2019, Springer Science+Business Media, LLC, part of Springer Nature

Differential effects of inotropes and inodilators on renal function in acute cardiac care

Pathological interplay between the heart and kidneys is widely encountered in heart failure (HF) and is linked to worse prognosis and quality of life. Inotropes, along with diuretics and vasodilators, are a core medical response to HF but decompensated patients who need inotropic support often present with an acute worsening of renal function. The impact of inotropes on renal function is thus potentially an important influence on the choice of therapy. There is currently relatively little objective data available to guide the selection of inotrope therapy but recent direct observations on the effects of levosimendan and milrinone on glomerular filtration favour levosimendan. Other lines of evidence indicate that in acute decompensated HF levosimendan has an immediate renoprotective effect by increasing renal blood flow through preferential vasodilation of the renal afferent arterioles and increases in glomerular filtration rate: potential for renal medullary ischaemia is avoided by an offsetting increase in renal oxygen delivery. These indications of a putative renoprotective action of levosimendan support the view that this calcium-sensitizing inodilator may be preferable to dobutamine or other adrenergic inotropes in some settings by virtue of its renal effects. Additional large studies will be required, however, to clarify the renal effects of levosimendan in this and other relevant clinical situations, such as cardiac surgery. © 2020 Oxford University Press. All rights reserved

Current drugs and medical treatment algorithms in the management of acute decompensated heart failure

Background: Acute decompensated heart failure (ADHF) is associated with increased hospitalization rates and high in-hospital mortality, and has emerged as a major public health problem over the past decade. In recent years, several new drugs and therapeutic approaches have failed to reduce short- and long-term morbidity and mortality in ADHF patients. New agents and strategies are under investigation in order to effectively reduce the mortality and morbidity in these patients. Objective: To review the recent experimental and clinical evidence on existing therapeutic algorithms and investigational drugs used for the treatment of ADHF. Methods: A systematic search of peer-reviewed publications was performed on Medline and EMBASE from January 1995 to January 2009. The results of unpublished trials were obtained from presentations at national and international meetings. Results: Renal dysfunction and low systolic blood pressure (SBP) remain the main predictors of adverse clinical outcomes in ADHF patients. Thus, therapy should be tailored according to the level of SBP at admission, renal function and fluid retention. ADHF due to hypertensive disease should be treated with intravenous vasodilators and diuretics at low doses, while patients with low output syndrome need mainly inotropic support. However, few agents currently employed in the treatment of ADHF have been shown in large prospective randomized clinical trials to improve clinical outcomes. The calcium sensitizer levosimendan is superior than traditional inotropes in improving central hemodynamics and neurohormonal response in ADHF patients, without increasing their long-term survival. Vasopressin antagonists also seem to be promising and safe drugs in the treatment of ADHF patients, facilitating diuresis on top of standard-care therapy. Encouraging novel therapies include adenosine receptor antagonists, ularitide, istaroxime, cardiac myosin activators and relaxin. Conclusions: Clinical scenarios based on SBP are essential determinants of therapeutic approaches used for the management of ADHF. Traditional drugs (diuretics, dobutamine and milrinone) have several limitations in real clinical practice, and increase mortality rates. Investigational drugs targeting to novel pathophysiologic concepts are promising treatment approaches and ongoing trials will define their clinical efficacy and safety. © 2009 Informa UK Ltd. All rights reserved

Selective serotonin re-uptake inhibitors for the treatment of depression in coronary artery disease and chronic heart failure: Evidence for pleiotropic effects

Depression is a common co-morbidity in patients with cardiovascular diseases such as chronic coronary artery disease, acute coronary syndromes, post by-pass surgery and chronic heart failure. There is a significant body of evidence suggesting that the presence of depression is independently associated with a decline in health status and an increase in the risk of hospitalization and death for patients with coronary artery disease or congestive heart failure. Novel treatment modalities such as selective serotonin re-uptake inhibitors (SSRIs) may improve depressive symptoms and prognosis of post-myocardial infarction and heart failure patients interacting with the common pathophysiologic mechanisms of depression and cardiovascular disease. This review summarizes current experimental and clinical evidence regarding the pleiotropic effects of SSRIs on platelet functions, immune and neurohormonal activation, and cardiac rhythm disturbances in patients with cardiovascular disease. These bio-modulatory properties of SSRIs may be translated into improvement of patient clinical outcomes beyond their anti-depressant action. © 2006 Bentham Science Publishers Ltd

Novel biologic mechanisms of levosimendan and its effect on the failing heart

Background: Calcium sensitizers belong to a new class of cardiac enhancers that stimulate cardiac contractility without causing intracellular calcium overload or increasing myocardial oxygen demand. Levosimendan, the most well-studied calcium sensitizer in the real clinical practice, produces greater hemodynamic and symptomatic improvement in patients with acute heart failure than traditional inotropes. Objective: To review the recent experimental and clinical evidence on novel biologic mechanisms explaining the pleiotropic effects of levosimendan on the falling heart. Methods: A systematic search of peer-reviewed publications was performed on Medline and EMBASE from January 1995 to December 2007. The results of unpublished trials were obtained from presentations at national and international meetings. Results: Levosimendan has a unique dual mechanism of action by enhancing cardiac contractility and causing peripheral vasodilatation. Immunomodulatory and antiapoptotic properties of levosimendan may be an additional biologic mechanism that prevents further cytotoxic and hemodynamic consequences of abnormal immune and neurohormonal respones in acute heart failure, leads to cardioprotection and beneficially intervenes in the progression of syndrome. Experimental data show that levosimendan exerts its cardioprotective effects through its antioxidant properties and seems to be a potent inhibitor of H2O2-induced cardiomyocyte apoptotic cell death. Clinical data demonstrate that levosimendan does not increase markers of oxidative and nitrosative stress, in contrast to placebo treatment, in advanced chronic heart failure patients. Levosimendan has also been shown to activate mitoKATP channels which are important mediators of ischemic preconditioning. Pharmacological modulation of KATP channels may prove beneficial in patients at risk of myocardial ischemia, particularly those requiring inotropic support. Conclusion: Pleiotropic effects of levosimendan appear to have important clinical and prognostic implications in acute heart failure syndromes and ischemic heart disease. © 2008 Informa UK Ltd

Complex atheromatous plaques in the descending aorta and the risk of stroke: A systematic review and meta-analysis

Background and Purpose: Proximal aortic plaques, especially in the aortic arch, have already been established as an important cause of stroke and peripheral embolism. However, aortic plaques situated in the descending thoracic aorta have recently been postulated as a potential embolic source in patients with cryptogenic cerebral infarction through retrograde aortic flow. The aim of the present study was to evaluate the potential association of descending aorta atheromatosis with cerebral ischemia. METHODS-: We conducted a systematic review and meta-analysis of all available prospective observational studies reporting the prevalence of complex atheromatous plaques in the descending aorta in patients with stroke and in unselected populations undergoing examination with transesophageal echocardiography. RESULTS-: We identified 11 eligible studies including a total of 4000 patients (667 patients with stroke and 3333 unselected individuals; mean age, 65 years; 55% men). On baseline transesophageal echocardiograpic examination, the prevalence of complex atheromatous plaques in the descending aorta was higher (P=0.001) in patients with stroke (25.4%; 95% confidence interval, 14.6-40.4%) compared with unselected individuals (6.1%; 95% confidence interval, 3.4-10%). However, no significant difference (P=0.059) in the prevalence of complex atheromatous plaques in the descending aorta was found between patients with cryptogenic (21.8%; 95% confidence interval, 17.5-26.9%) and unclassified (28.3%; 95% confidence interval, 23.9-33.1%) cerebral infarction. CONCLUSIONS-: Our findings indicate that the presence of complex plaques in the descending aorta is presumably a marker of generalized atherosclerosis and high vascular risk. The present analyses do not provide any further evidence for a direct causal relationship between descending aorta atherosclerosis and cerebral embolism. © 2014 American Heart Association, Inc

Effects of Darbepoetin Alfa on Plasma Mediators of Oxidative and Nitrosative Stress in Anemic Patients With Chronic Heart Failure Secondary to Ischemic or Idiopathic Dilated Cardiomyopathy

Increased oxidative and nitrosative stress are important mediators of left ventricular (LV) and vascular dysfunction in patients with chronic heart failure (CHF). This study investigated the effects of darbepoetin alfa on plasma markers of oxidative and nitrosative stress in patients with CHF with anemia. Thirty patients with CHF (LV ejection fraction [LVEF] <40%, hemoglobin <12.5 g/dl, and serum creatinine <2.5 mg/dl) were randomly assigned (1:1) to receive either a 3-month darbepoetin alfa regimen at 1.5 μg/kg every 20 days plus oral iron or placebo plus oral iron. Plasma B-type natriuretic peptide (BNP), markers of oxidative (oxidative, malondialdehyde, carbonyl proteins; antioxidative, glutathione) and nitrosative (nitrotyrosine) stress, LVEF, and 6-minute walked distance were assessed at baseline and after treatment. A significant improvement in LVEF and 6-minute walked distance was observed in only darbepoetin-treated patients. Plasma BNP (F = 14.8, p = 001), malondialdehyde (F = 9.4, p = 0.006), protein carbonyl (F = 9.2, p = 0.006), and nitrotyrosine (F = 4.4, p = 0.045) were significantly decreased, along with an increase in antioxidative glutathione (F = 4.2, p = 0.049) after darbepoetin alfa treatment. These factors were unaffected in placebo-treated patients. Darbepoetin-induced percentages of change in carbonyl protein significantly correlated with respective changes in plasma BNP (r = 0.55, p <0.05) and LVEF (r = -0.46, p <0.05). Finally, a drug-induced percentage of decrease in nitrotyrosine significantly correlated with the respective improvement in 6-minute walked distance (r = -0.63, p <0.05). In conclusion, darbepoetin alfa attenuated deleterious effects of oxidative and nitrosative stress into the cardiovascular system of anemic patients with CHF, improving also cardiac function and exercise capacity. © 2009 Elsevier Inc. All rights reserved

Effects of Levosimendan on circulating markers of oxidative and nitrosative stress in patients with advanced heart failure

Background: Oxidative stress is associated with maladaptive cardiac remodeling and vascular dysfunction and may be an important contributor to chronic heart failure (CHF) deterioration. We sought to investigate if the calcium sensitizer levosimendan beneficially modulates circulating markers of oxidative and nitrosative stress thus lessening their deleterious effects in patients with advanced CHF. Methods: Thirty-nine patients with advanced CHF (mean NYHA 3.5 ± 0.4; ischemic/dilated: 23/16; mean left ventricular ejection fraction: 26 ± 7%) who were hospitalized due to syndrome worsening, were randomized (2:1) to receive either a 24-h levosimendan infusion of 0.1 μg/(kg min) (n = 26) or placebo (n = 13). Plasma b-type natriuretic peptide (BNP), circulating markers of oxidative [protein carbonyls, malondialdehyde (MDA)] and nitrosative (nitrotyrosine) stress, and cyclic GMP (cGMP) were measured at baseline and 48 h after each treatment. Results: Baseline characteristics and medications were well balanced in the two treatment groups. A significant improvement in left ventricular ejection fraction (P < 0.01), NYHA class (P < 0.01), and plasma BNP (P < 0.01) was observed post-treatment only in the levosimendan group. Markers such as MDA, protein carbonyls and nitrotyrosine remained stable in the levosimendan-treated group, but significantly increased (P < 0.05) in the placebo-treated patients. Neither therapeutic intervention changed the levels of circulating cGMP. Conclusion: Levosimendan does not increase markers of oxidative and nitrosative stress in contrast to the placebo treatment, thus, exerting cardioprotective effects in advanced CHF patients. Moreover, levosimendan may exert its biologic action through non-cGMP-dependent biochemical pathways. © 2007 Elsevier Ireland Ltd. All rights reserved

Acute pulmonary oedema: Clinical characteristics, prognostic factors, and in-hospital management

AimsAcute pulmonary oedema (APE) is the second, after acutely decompensated chronic heart failure (ADHF), most frequent form of acute heart failure (AHF). This subanalysis examines the clinical profile, prognostic factors, and management of APE patients (n = 1820, 36.7) included in the Acute Heart Failure Global Survey of Standard Treatment (ALARM-HF). Methods and resultsALARM-HF included a total of 4953 patients hospitalized for AHF in Europe, Latin America, and Australia. The final diagnosis was made at discharge, and patients were classified according to European Society of Cardiology guidelines. Patients with APE had higher in-hospital mortality (7.4 vs. 6.0, P = 0.057) compared with ADHF patients (n = 1911, 38.5), and APE patients exhibited higher systolic blood pressures (P < 0.001) at admission and higher left ventricular ejection fraction (LVEF, P < 0.01) than those with ADHF. These patients also had a higher prevalence of diabetes (P < 0.01), arterial hypertension (P < 0.001), peripheral vascular disease (P < 0.001), and chronic renal disease (P < 0.05). They were also more likely to receive intravenous (i.v.) diuretics (P < 0.001), i.v. nitrates (P < 0.01), dopamine (P < 0.05), and non-invasive ventilation (P < 0.001). Low systolic blood pressure (P < 0.001), low LVEF (<0.05), serum creatinine ≥1.4 mg/dL (P < 0.001), history of cardiomyopathy (P < 0.05), and previous cardiovascular event (P < 0.001) were independently associated with increased in-hospital mortality in the APE population. ConclusionAPE differs in clinical profile, in-hospital management, and mortality compared with ADHF. Admission characteristics (systolic blood pressure and LVEF), renal function, and history may identify high-risk APE patients. © 2010 The Author