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 reno-protective 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.

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.

Use of levosimendan in acute heart failure.

As a calcium sensitizer and inodilator that augments cardiac contractility without increasing myocardial oxygen demand or exacerbating ischaemia, levosimendan may be well configured to deliver inotropic support in cases of acute heart failure (AHF). Other factors favouring levosimendan in this setting include its extended duration of action due to the formation of an active metabolite and the lack of any attenuation of effect in patients treated with beta-blockers. Effects of levosimendan on systemic haemodynamics include its significant, dose-dependent increases in cardiac output, stroke volume and heart rate, and decreases in right and left ventricular filling and total peripheral resistance. Rapid and sustained reduction in levels of natriuretic peptides is a consistent effect of levosimendan use and potentially favourable effects on other neurohormonal indicators of cardiac distress are also observed. Levosimendan has repeatedly been shown to be effective in relief of symptoms of AHF, notably dyspnoea and fatigue, while mortality data from clinical trials and registries suggest that levosimendan is markedly less likely than catecholaminergic inotropes to worsen prognosis. The vasodilator pharmacology of levosimendan is also pertinent to the drug's use in AHF, in which setting organ under-perfusion is often a key pathology. These considerations suggest that levosimendan may have a more favourable impact on the circumstances of the majority of AHF patients than adrenergic agents that act only or primarily as cardiac stimulants. They also suggest that levosimendan may advantageously be integrated into a comprehensive strategy of early intervention designed and intended to prevent cardiac destabilization worsening to the point where hospitalization is necessary. Levosimendan should be used with caution and with tightened haemodynamic monitoring in patients who have low baseline blood pressure (systolic blood pressure <100 mmHg; diastolic blood pressure <60 mmHg), or who are at risk of a hypotensive episode.

Acute Heart Failure Syndromes in the Elderly: The European Perspective.

Acute heart failure (AHF) in the elderly is an increasingly common clinical problem associated with high in-hospital, short- and long-term mortality rates worldwide. Elderly patients with AHF have different clinical and pathophysiological profiles compared with younger ones. Prevalent cardiovascular comorbidities in the elderly are arterial hypertension and atrial fibrillation, whereas ischemic heart disease and associated risk factors are more common in younger patients. There is a need for greater dissemination of heart failure guidelines and for involvement of multidisciplinary teams for optimizing treatment and eliminating disparities in care in this vulnerable patient group across both sides of the Atlantic.

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.

Implementation of a Cardiogenic Shock Team in a Tertiary Academic Centre.

BACKGROUND: Observational studies have shown that the management of patients with cardiogenic shock (CS) by dedicated multidisciplinary teams improve clinical outcomes. Nevertheless, these studies reflect a specific organisational setting with most patients being transfers from referring hospitals, hospitalised in cardiac intensive care units (ICU), or treated with mechanical circulatory support (MCS) devices. The purpose of this study was to document the organisation and outcomes of a CS team offering acute care in all-comer population. METHODS: A CS team was developed in a large academic tertiary institution. The team consisted of emergency care physicians, critical care cardiologists, interventional cardiologists, cardiac surgeons, ICU physicians and heart failure specialists and was supported by predefined operating protocol, dedicated communication platform and regular team meetings. RESULTS: Over 12 months, 70 CS patients (69±13 years old, 67% males) were included. Acute myocardial infarction (AMI-CS) was the most common cause (64%); 31% of the patients presented post-resuscitated cardiac arrest and 56% needed invasive mechanical ventilation (IMV). Coronary angiography was performed in 70% and 53% had percutaneous coronary intervention. MCS was used in 10% and 6% were referred for urgent cardiac surgery. The in-hospital mortality in our centre was 40% with 39% of the patients dying within 24-hours from presentation. 76% of the alive patients were discharged home. CONCLUSIONS: Across an all-comer population, AMI was the most common cause of CS. A significant number of patients presented post cardiac arrest, and the majority required IMV. Mortality was high with a significant number dying within hours of presentation.

Functional electrical stimulation of peripheral muscles improves endothelial function and clinical and emotional status in heart failure patients with preserved left ventricular ejection fraction.

BACKGROUND: Functional electrical stimulation (FES) improves exercise capacity, quality of life, emotional stress, and endothelial function in chronic heart failure with impaired systolic function. We sought to investigate the effects of FES on the above parameters in patients with preserved ejection fraction (HFpEF). METHODS: Thirty HFpEF patients, 18 female and 12 male, aged 69 ± 8 years, in New York Heart Association class II or III and with mean ejection fraction 63% ± 6%, were randomly (1:1) assigned to a 6-week FES program or placebo. Assessment was performed at baseline and after completion of training protocol and included 6-minute walked distance, quality of life (Kansas City Cardiomyopathy Questionnaire and Minnesota Living with Heart Failure Questionnaire), depressive symptoms (Beck Depression Inventory and Zung self-rated depression scores), B-type natriuretic peptide, endothelial function (flow-mediated dilatation), and left ventricular diastolic function. RESULTS: A significant improvement in 6-minute walked distance (F = 21.61, P = .001), Kansas City Cardiomyopathy Questionnaire summary (F = 8.68, P = .006), Minnesota Living with Heart Failure Questionnaire (F = 6.43, P = .017), Beck Depression Inventory (F = 6.66, P = .015), Zung (F = 6.25, P = .019), and flow-mediated dilatation diameter (F = 11.98, P = .002) was observed in the FES group compared with placebo group; B-type natriuretic peptide also declined but not significantly (F = 0.249, P = .622), and there was a tendency toward lower mitral E/e' wave ratio (F = 3.066, P = .091). CONCLUSION: As in heart failure and reduced left ventricular ejection fraction, FES also improves exercise capacity, quality of life, emotional status, and endothelial function in HFpEF. Given the lack of effective evidence-based therapies in these patients, FES warrants further investigation.

Renal effects of levosimendan: a consensus report.

Renal dysfunction is common in clinical settings in which cardiac function is compromised such as heart failure, cardiac surgery or sepsis, and is associated with high morbidity and mortality. Levosimendan is a calcium sensitizer and potassium channel opener used in the treatment of acute heart failure. This review describes the effects of the inodilator levosimendan on renal function. A panel of 25 scientists and clinicians from 15 European countries (Austria, Finland, France, Hungary, Germany, Greece, Italy, Portugal, the Netherlands, Slovenia, Spain, Sweden, Turkey, the United Kingdom, and Ukraine) convened and reached a consensus on the current interpretation of the renal effects of levosimendan described both in non-clinical research and in clinical study reports. Most reports on the effect of levosimendan indicate an improvement of renal function in heart failure, sepsis and cardiac surgery settings. However, caution should be applied as study designs differed from randomized, controlled studies to uncontrolled ones. Importantly, in the largest HF study (REVIVE I and II) no significant changes in the renal function were detected. As it regards the mechanism of action, the opening of mitochondrial KATP channels by levosimendan is involved through a preconditioning effect. There is a strong rationale for randomized controlled trials seeking beneficial renal effects of levosimendan. As an example, a study is shortly to commence to assess the role of levosimendan for the prevention of acute organ dysfunction in sepsis (LeoPARDS).

Optimal use of intravenous landiolol in acute cardiac care.

INTRODUCTION: B-blockers are regarded as beneficial pharmacologic agents in cardiac care, but their role in the acute setting remains ambiguous. Increasing evidence supports the important role of landiolol in critical care, a highly cardioselective intravenous b-blocker with rapid onset of action and short elimination time. Among its most valuable properties, which may aid to overcome special reservations related to b-blocker therapy in the acute setting, landiolol has a potent negative chronotropic effect while at the same time it exhibits a mild negative inotropic effect. AREAS COVERED: This expert opinion review aims to present basic pharmacologic aspects of landiolol and provide current clinical research focused on its efficacy and safety. EXPERT OPINION: Landiolol is a valuable and safe pharmacologic agent in acute cardiac care. Japanese and European guidelines have incorporated its use for the management of atrial tachyarrhythmia in patients with cardiac dysfunction. Although emerging clinical trials have experimented its use in patients with sustained ventricular tachycardia/fibrillation, acute myocardial infarction undergoing primary percutaneous intervention and in patients with septic cardiomyopathy, more studies are needed in order to establish its value in such cardiac conditions.

Effects of sertraline on circulating markers of oxidative stress in depressed patients with chronic heart failure: a pilot study.

BACKGROUND: Depression is a common comorbid condition in patients with chronic heart failure (CHF). This pilot study investigated the plasma levels of oxidative stress markers in depressed CHF patients as well as the effects of antidepressant treatment with sertraline on these markers in the same patient population. METHODS AND RESULTS: Patients with positive depression screening [Beck Depression Inventory (BDI) score >10 and/or Zung Self-Rating Depression Scale >40] underwent a psychiatric interview. Patients newly diagnosed as depressed received pharmacologic treatment with sertraline for 3 months (arm A) and were compared with those who did not comply with the antidepressant treatment (arm B). Markers of oxidative stress [malondialdehyde (MDA) and protein carbonyls (PC)], and nitrosative stress [nitrotyrosine (NT)] were assessed at baseline and 3 months later. Fifty-two out of 254 screened hospitalized CHF patients were diagnosed as depressed. Depressed patients had significantly higher levels of MDA compared with age- and gender-matched nondepressed patients (n = 40; 3.2 ± 2.0 vs 2.8 ± 3.8 µmol/L; P = .02). Twenty-eight patients received sertraline (arm A), and 24 refused to receive antidepressant treatment on the top of optimal heart failure treatment (arm B). Although baseline levels of MDA and PC in arm A and arm B did not differ significantly (P > .05), arm A patients demonstrated a significant reduction in MDA (F = 4.657; P = .037) and arm B patients demonstrated no change after 3 months. Regarding the examined scores, arm A patients had a decrease in BDI score (28 ± 11 vs 21 ± 13; P = .008), and arm B patients had no change in BDI score at follow-up (P > .05). Arm A had an increase in 6-minute walking distance (291 ± 110 vs 361 ± 87 m; P = .02), and arm B experienced no change (P > .05). CONCLUSIONS: Increased oxidative stress may play a critical role in the pathophysiology of depression in CHF. Treatment with sertraline improves depressive symptoms and reduces plasma markers of oxidative stress in depressed CHF patients.

Functional electrical stimulation is more effective in severe symptomatic heart failure patients and improves their adherence to rehabilitation programs.

BACKGROUND: Functional electrical stimulation (FES) improves exercise capacity and quality of life in chronic heart failure (CHF) patients. However, there is no evidence regarding the effectiveness of this treatment modality according to the severity of CHF. This study compares the effectiveness of FES on exercise capacity, endothelial function, neurohormonal status, and emotional stress in New York Heart Association (NYHA) III-IV versus NYHA II patients. METHODS AND RESULTS: Eighteen NYHA II and 13 age- and sex-matched NYHA III-IV patients with stable CHF (left ventricular ejection fraction <35%) underwent a 6-week FES training program. Questionnaires addressing quality of life (Kansas City Cardiomyopathy Questionnaire, functional and overall), and emotional stress (Zung self-rating depression scale, Beck Depression Inventory), as well as plasma B-type natriuretic peptide (BNP), 6-minute walking distance test (6MWT), and endothelial function (flow-mediated dilatation [FMD]) were assessed at baseline and after completion of training protocol. 6MWT and plasma BNP improved significantly in 2 patient groups (both P < .001) after training program. The improvement of BNP was statistically greater in NYHA III-IV patients posttreatment than in those with NYHA II class (F=315.342, P < .001). Similarly, the improvement of 6MWT was statistically greater in NYHA III-IV group than in NYHA II patients (F=79.818, P < .001). Finally, an FES-induced greater improvement of FMD (F=9.517, P=.004) and emotional stress scores was observed in NYHA III-IV patients in comparison to NYHA II patients. There was a higher proportion of NYHA III-IV patients adhering to the FES training program for additional 3 months compared with the NYHA II group of patients (76.9% vs. 55.6%, P < .001). CONCLUSION: FES might exert a greater beneficial effect on clinical and neurohormonal status of NYHA III-IV patients in comparison to NYHA II patients. This effect may have important clinical relevance leading to increased adherence of severe CHF patients to exercise rehabilitation programs.

Inotropes in cardiac patients: update 2011.

PURPOSE OF REVIEW: ICU patients frequently develop low output syndromes due to cardiac dysfunction, myocardial injury, and inflammatory activation. Conventional inotropic agents seem to be useful in restoring hemodynamic parameters and improving peripheral organ perfusion, but can increase short-term and long-term mortality in these patients. Novel inotropes may be promising in the management of ICU patients, having no serious adverse effects. This review summarizes all the current knowledge about the use of conventional and new inotropic agents in various clinical entities of critically ill patients. RECENT FINDINGS: In recent European Society of Cardiology guidelines, inotropic agents are administered in patients with low output syndrome due to impaired cardiac contractility, and signs and symptoms of congestion. The most recommended inotropes in this condition are levosimendan and dobutamine (both class of recommendation: IIa, level of evidence: B). Recent data indicate that levosimendan may be useful in postmyocardial infarction cardiac dysfunction and septic shock through increasing coronary flow and attenuating inflammatory activation, respectively. Furthermore, calcium sensitizing by levosimendan can be effectively used for weaning of mechanical ventilation in postcardiac surgery patients and has also cardioprotective effect as expressed by the absence of troponin release in this patient population. Finally, new agents, such as istaroxime and cardiac myosin activators may be safe and improve central hemodynamics in experimental models of heart failure and heart failure patients in phase II clinical trials; however, large-scale randomized clinical trials are required. SUMMARY: In an acute cardiac care setting, short-term use of inotropic agents is crucial for the restoration of arterial blood pressure and peripheral tissue perfusion, as well as weaning of cardiosurgery. New promising agents should be tested in randomized clinical trials.

HEllenic Registry on Myocarditis SyndromES on behalf of Hellenic Heart Failure Association: The HERMES-HF Registry.

AIMS: Despite the existence of many studies, there are still limited data about the characteristics of myocarditis in Greece. This led to the creation of the Greek Myocarditis Registry aiming to document the different symptoms and treatment of myocarditis, assess possible prognostic factors, and find similarities and differences to what is already published in literature. This paper is a preliminary descriptive analysis of this Registry. METHODS AND RESULTS: We analysed data for the hospitalization period of all patients included in the Registry from December 2015 until November 2017. Statistics are reported as frequency (%) or median and inter-quartile range (IQR) as appropriate. In total, 146 patients were included; 83.3% of the patients reported an infection during the last 3 months. The most common symptom, regardless of the underlying infection, was chest pain (82.2%) followed by dyspnoea (18.5%), while the most common finding in clinical examination was tachycardia (26.7%). Presentation was more frequent in the winter months. ECG findings were not specific, with the repolarization abnormalities being the most frequent (60.3%). Atrial fibrillation was observed in two patients, both of whom presented with a reduced ventricular systolic function. Left ventricular ejection fraction changed significantly during the hospitalization [55% (IQR: 50-60%) on admission vs. 60% (IQR: 55-60%) on discharge, P = 0.0026]. Cardiac magnetic resonance was performed in 88 patients (61%), revealing mainly subepicardial and midcardial involvement of the lateral wall. Late gadolinium enhancement was present in all patients, while oedema was found in 39 of them. Only 11 patients underwent endomyocardial biopsy. Discharge medication consisted mainly of beta-blockers (71.9%) and angiotensin-converting enzyme inhibitors (41.8%), while 39.7% of the patients were prescribed both. CONCLUSIONS: This preliminary analysis describes the typical presentation of myocarditis patients in Greece. It is a first step in developing a better prognostic model for the course of the disease, which will be completed after the incorporation of the patients' follow-up data.

Levosimendan: from basic science to clinical practice.

Levosimendan is a new cardiac enhancer that exerts positive inotropic effects on the failing heart mediated by calcium sensitization of contractile proteins as well as peripheral vasodilatory effects mediated by opening of ATP-sensitive potassium channels in vascular smooth-muscle cells. Levosimendan is the most well-studied calcium sensitizer in the real clinical practice, producing greater hemodynamic and symptomatic improvement in patients with acute heart failure syndromes (AHFS) than those with traditional inotropes. Immunomodulatory and anti-apoptotic properties of levosimendan may be an additional biologic mechanism that prevents further cytotoxic and hemodynamic consequences of abnormal immune and neurohormonal responses in AHFS. Recent mortality trials showed that levosimendan does not improve short- and long-term prognosis in AHFS in comparison to dobutamine or placebo. However, in patients with a previous history of CHF and on beta-blocker on admission, levosimendan seems to have a beneficial effect on short-term mortality. According to the recent guidelines of the European Society of Cardiology, levosimendan is indicated in patients with symptomatic low cardiac output HF secondary to cardiac systolic dysfunction without severe hypotension (Class IIa, Level of Evidence B).

Self-assessment of health status is associated with inflammatory activation and predicts long-term outcomes in chronic heart failure.

AIMS: Clinicians lack a generally accepted means for health status assessment in chronic heart failure (CHF). We investigated the correlation between health status and inflammation burden as well as its long-term prognostic value in CHF outpatients. METHODS AND RESULTS: Kansas City Cardiomyopathy Questionnaires (KCCQ) were completed by 137 CHF outpatients (aged 64+/-12 years, mean ejection fraction 27+/-7%). Inflammatory markers [interleukin (IL)-6, IL-10, TNF-alpha, soluble Fas, Fas ligand, ICAM-1, VCAM-1], plasma B-type natriuretic peptide (BNP), 6 min walk test (6MWT), Zung self-rating depression scale, and Beck Depression Inventory were also assessed. Patients were followed for major cardiovascular events (death or hospitalization for disease progression) for up to 250 days. Patients with worse KCCQ-summary (KCCQ-s<50) score had lower 6MWT (P<0.05), and higher BNP (P<0.05) and pro-inflammatory markers (P<0.05) than those with KCCQ-s>or=50. Worse health status was also associated with shorter event-free survival (115+/-12 days for KCCQ-s<50 vs. 214+/-15 days for KCCQ-s>or=50, P=0.0179). Separating patients according KCCQ-functional score (KCCQ-f, cut-off 50) showed similar results. In multivariate Cox regression analysis, only LVEF (HR=0.637, 95% CI 0.450-0.900, P=0.011) and KCCQ-f (HR=0.035, 95% CI 0.002-0.824, P=0.037) were independent predictors of event-free survival at 250 days. CONCLUSION: KCCQ-s reflects neurohormonal and inflammatory burden in CHF. Among studied questionnaires, only KCCQ-f is an independent predictor of long-term event-free survival in CHF.

Pharmacologic stabilization and management of acute heart failure syndromes in the emergency department.

Effective use of diuretics, vasodilators, and inotropes to stabilize acute heart failure (AHF) relies on matching the most appropriately tailored therapy to specific clinical profiles. Some of the drugs may be harmful, and therefore the emphasis should be on patient safety and the attempt to minimize the deleterious effects of these therapies. To date, successful treatment has been limited because no agent has been shown to reduce postdischarge mortality or readmission rates, and patients frequently remain symptomatic after treatment. Ongoing research is needed to further examine these agents and to develop novel therapies to address the unmet needs of the patient who has AHF.

Effects of darbepoetin alpha on right and left ventricular systolic and diastolic function in anemic patients with chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

BACKGROUND: Anemia is a frequent condition in chronic heart failure (CHF) that affects adversely long-term cardiac outcomes. We sought to investigate the effects of recombinant human erythropoietin analogue darbepoetin alpha on left (LV) and right ventricular (RV) function and neurohormonal activation in patients with CHF and anemia. METHODS: Thirty-two CHF patients (New York Heart Association class II-III, LV ejection fraction [EF] <40%, hemoglobin level <12.5 g/dL, serum creatinine level <2.5 mg/dL) were randomized (2:1) to receive either a 3-month darbepoetin alpha regimen at 1.5 microg/kg every 20 days plus oral iron (n = 21) or placebo plus oral iron (n = 11). Echocardiographic indices of LV systolic and diastolic function and RV function, plasma B-type natriuretic peptide (BNP) and 6-minute walked distance were assessed at baseline and posttreatment. RESULTS: Regarding LV function, only treatment with darbepoetin alpha caused a significant improvement in LVEF (F = 22.001, P < .001), end-systolic wall stress (F = 4.934, P = .034), mitral annulus systolic displacement (F = 6.710, P < .015), isovolumic relaxation time (F = 4.909, P = .035), and E/e ratio (F = 7.833, P = .009). The RV systolic pressure (F = 7.715, P = .009) as well as tricuspid annulus systolic displacement and RVEF (F = 9.264, P = .005) were significantly improved only in the darbepoetin alpha group. Darbepoetin alpha had also alpha beneficial effect on New York Heart Association class (F = 14.586, P = .001), plasma BNP (F = 14.781, P = .001), and 6-minute walk test (F = 19.926, P < .001), whereas these parameters did not significantly change in the placebo-treated patients. CONCLUSION: Darbepoetin alpha improves both LV and RV performance and exercise capacity and counteracts neurohormonal activation in CHF patients with anemia. The drug effects on LV diastolic function, RV function, and LV end-systolic wall stress, in particular, are novel findings, with a potential important contribution to patients' symptomatic improvement.

Overview of emerging pharmacologic agents for acute heart failure syndromes.

BACKGROUND: Several therapies commonly used for the treatment of acute heart failure syndromes (AHFS) present some well-known limitations and have been associated with an early increase in the risk of death. There is, therefore, an unmet need for new pharmacologic agents for the early management of AHFS that may improve both short- and long-term outcomes. AIM: To review the recent evidence on emerging pharmacologic therapies in AHFS. METHODS: A systematic search of peer-reviewed publications was performed on MEDLINE, EMBASE and Clinical Trials.gov from January 1990 to August 2007. The results of unpublished or ongoing trials were obtained from presentations at national and international meetings and pharmaceutical industry releases. Bibliographies from these references were also reviewed, as were additional articles identified by content experts. RESULTS: Cumulative data from large studies and randomised trials suggest that therapies with innovative mechanisms of action may safely and effectively reduce pulmonary congestion or improve cardiac performance in AHFS patients. CONCLUSION: Some investigational agents for the management of AHFS are able to improve haemodynamics and/or clinical status. In spite of these promising findings, no new agent has demonstrated a clear benefit in terms of long-term clinical outcomes compared to placebo or conventional therapies.