TDT: a highly potent and stable chimeric natriuretic peptide for heart failure treatment

2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC.

Pleural Effusion in Congestive Heart Failure

Renal dysfunction is a common and progressive complication of chronic heart failure, with a clinical course that typically fluctuates with the patient’s clinical status and treatment. Despite growing recognition of the frequent presentation of combined cardiac and renal dysfunction, or “cardiorenal syndrome,” its underlying pathophysiology is not well understood, and no consensus as to its appropriate management has been achieved. Because patients with heart failure are surviving longer and dying less frequently from primary arrhythmia, we expect that the cardiorenal syndrome will become more common. Against this background, the article by Wang and colleagues1 in the present issue of Circulation is particularly significant because it is the first prospective, controlled therapeutic trial in patients with this condition. To place the findings and implications of this study in context, we first briefly review what is currently known about the cardiorenal syndrome and its treatment options. See p 1620 In ambulatory heart failure patients, the presence of concomitant renal dysfunction consistently has been one of the strongest risk factors for mortality.2–4 This risk becomes evident even at serum creatinine clearance levels >1.3 mg/dL and estimated creatinine clearance values ≤60 to 70 mL/min. Furthermore, renal function is at least as powerful an adverse prognostic factor as most clinical variables, including ejection fraction and New York Heart Association function class. Although renal dysfunction predicts all-cause mortality, it is most predictive of death from progressive heart failure, which suggests that it is a manifestation of and/or exacerbating factor for left ventricular dysfunction.2 In the setting of hospitalization for decompensated heart failure, worsening renal function is even more important than baseline renal function for predicting adverse outcomes.5–8 Although any increase in creatinine is associated with poorer survival rates, longer hospitalization, and more frequent readmission, several studies have used a threshold of a …

It is now becoming clear that two major systems namely the sympathetic nervous system and the renin-angiotensin system are activated in response to ischemic injury; these result in the elevation of plasma catecholamines and angiotensin II during the development of myocardial infarction as well as congestive heart failure. Although plasma levels of several other hormones including aldosterone, endothelin, vasopressin, natriuretic peptides, growth factors and inflammatory cytokines are also increased in heart failure, their relationship with changes in catecholamine and/or angiotensin levels as well as their significance for the induction of congestive heart failure are poorly understood. In this article we have examined the evidence regarding the role of endothelin and vasopressin in the pathogenesis of cardiac hypertrophy and congestive heart failure in addition to evaluating the significance of their antagonism by using their receptor blockade for treatment of congestive heart failure. Endothelin appears to maintain blood pressure by its vasoconstricting action whereas vasopressin primarily produces similar effect by retention of body fluid. Myocardium is also known to express both ET-A and ET-B receptors in addition to V1 and V2 receptors for vasopressin, which have been shown to induce cardiac remodeling. Out of various ET-1 receptor antagonists, which are available, a non-selective endothelin receptor antagonist, bosentan, as well as an ET-A receptor antagonist, BQ-123, seem most promising for the treatment of congestive heart failure. Likewise, vasopressin antagonists such as a non-selective antagonist, conivaptan, as well as V2 selective antagonist, tolvaptan, may prove highly valuable for the therapy of this condition. Since most of the existing interventions are helpful in treating patients with congestive heart failure only partially, there appears to be a real challenge for developing some combination therapy for the treatment of congestive heart failure.

Neutral endopeptidase inhibition: the potential of a new therapeutic approach in cardiovascular disease evolves.

Cardiorenal Actions of the Designer Natriuretic Peptide, CD-NP, in a Severe Heart Failure Model Treated with Furosemide

Summary: Congestive heart failure (CHF) is a complex clinical syndrome in which the kidney has a central pathophysiological role. an imbalance between vasoconstrictor‐antinatriuretic and vasodilator‐natriuretic forces is a key feature of the pathophysiology of CHF. This review summarizes current understanding of disturbances in vasodilator‐natriuretic systems in CHF. the key vasodilator systems involved are: the natriuretic peptide family atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), urodilatin, dopamine (DA), endothelium‐derived relaxing factors and prosraglandins. Renal responses to ANP are blunted in CHF, under the influence of haemodynamic, neuro‐humoral, receptor and post‐receptor events. BNP, secreted in response to left ventricular load, may circulate in high concentrations in CHF, with similar effects to ANP. Urodilatin is a newly discovered peptide of renal origin whose physiological role is under investigation. Neural endopeptidase inhibitors have shown some promise in the treatment of human CHF, particularly when combined with ACE inhibition or angiotensin II receptor blockade. the renal DA system is influenced by sodium intake and DA metabolism is altered in CHF. the place of orally active DA prodrugs and DA agonist in the management of patients with CHF is still undecided. In CHF, basal release of nitric oxide may be preserved or even enhanced. However, stimulated release of nitric oxide may be reduced. Renal effects of nitric oxide or arginine in CHF have yet to be defined. Renal prostaglandins play an important role in offsetting renal and systemic vasoconstriction and fluid retention in CHF. the recent availability of specific receptor antagonist should lead to clearer definition of the relative roles of renal angiotensin II inhibition and bradykinin potentiation in the benefical responses to angiotensin converting enzyme (ACE‐1) in CHF. Prostaglandin‐E1 (PG‐E1) and prostaglandin‐E2 (PG‐E2) infusion may have some benefit for the treatment of severe CHF. Adrenomedullin, a vasodilator‐natriuretic peptide closely related to the calcitonin gene‐related peptide family, is present in high concentrations in the kidney. Plasma concentrations of adrenomedullin are increased after acute cardiac injury and in CHF. Its roles in renal physiology and in the pathophysiology of CHF are under investigation. Overall, there is considerable potential to exploit these vasodilator‐natriuretic systems in management strategies for CHF.

Successes and failures of current treatment of heart failure

Comorbidities in heart failure: a key issue

182 To Admit or Discharge Congestive Heart Failure Patients: Use of a Severity of Illness Index

Cardiac myosin-binding protein C as a candidate biomarker in heart failure: rational but not revolutionary.

Excerpt The use of ion exchange resins was suggested by Segal et al.2for control of gastric acidity and by Dock3for treatment of cardiac edema. The background and theory of ion exchange by resins i...

New heart failure guidelines offer a changing landscape

In 1628, Harvey first correctly described the heart as a pump. It was another 350 years before the heart was established as an endocrine gland that synthesized a family of peptide hormones that regulate blood volume and blood pressure. There are now five peptide hormones made in the heart which have been demonstrated to have beneficial effects in persons with congestive heart failure. One of these peptide hormones i.e. brain natriuretic peptide (BNP) is commercially available and has been widely used in the United States for the treatment of acute congestive heart failure under the name Nesiritide/Natrecor. Nesiritide has one serious side effect, i.e. it may worsen renal function in persons with acute decompensated cardiac failure. The best of these peptide hormones for the treatment of chronic heart failure is a cardiac hormone named vessel dilator which enhances sodium and water excretion 4- to 5-fold in persons with congestive heart failure but vessel dilator's biologic effects lasts six hours compared to less than 30 minutes for BNP, without the deleterious effects of BNP on renal function. This review will focus on six cardiac hormones' discovery, identification and comparison of their beneficial effects and side effects in humans with congestive heart failure.

Blood pressure lowering, renin suppressing and natriuretic properties of a new designer peptide BD-NP