Use of Natriuretic Peptides as a Guidance for Treating Patients with Chronic Heart Failure: Unresolved Issues and Novel Insights

Abstract: Serial measurements of natriuretic peptides (NPs), i.e. B-type natriuretic peptide (BNP) or amino-terminal fragment of pro B-type natriuretic peptide (NT-pro BNP), may serve as an objective guide to modulate the intensity of drug treatment for individuals with chronic heart failure (CHF). However, considerable uncertainty remains about the alleged useful role of NP-guided therapy in this context. Particularly, which NP level should be assumed as optimal target level for therapy is still matter of debate. Actually, a too low predetermined cut off is encumbered with the risk of inducing a dose escalation perhaps not founded on solid rationale but provided with the potential of propitiating adverse medication effects that may be associated with higher doses. Conversely, a too high predetermined level for NP would entail a poor sensitivity, with the potential of excluding from higher doses of medications, that are proven to increase survival, just the patients who above all would have benefitted from this uptitration. Another much debated issue is constituted by possible age-related differences concerning the effects on clinical endpoints of NP-guided therapy. In addition, some Authors dispute about the possible advantages for the cardiovascular system arising from the functional activation of NPs in CHF patients, so denying that their increased levels have to be per se blamed for hemodynamic upheaval, especially in elder CHF patients. After outlining the main RCTs carried out so far, the Authors stress the above reported issues and discuss the sometime contradictory results of the RCTs exploring NPs use as a guidance for therapy

Phosphodiesterase-5 Inhibitors Improve Clinical Outcomes, Exercise Capacity and Pulmonary Hemodynamics in Patients With Heart Failure With Reduced Left Ventricular Ejection Fraction: A Meta-Analysis

Several studies have compared the use of phosphodiesterase-5 (PDE5) inhibitors sildenafil or udenafil with the placebo in patients suffering from pulmonary hypertension (PH) due to left chronic heart failure (CHF), corresponding to group 2 (PH due to left heart disease) of the PH classification (according to 2015 ESC/ERS guidelines for the diagnosis and treatment of PH). The results of the use of PDE5 inhibitors in the PH due to left heart disease were inconsistent and heterogeneous. Therefore, we carried out a meta-analysis to assess the effect of PDE5 inhibitors in this clinical setting, i.e., patients with left CHF

Does Accidental Overcorrection of Symptomatic Hyponatremia in Chronic Heart Failure Require Specific Therapeutic Adjustments for Preventing Central Pontine Myelinolysis?

This review aims at summarizing essential aspects of epidemiology and pathophysiology of hyponatremia in chronic heart failure (CHF), to set the ground for a practical as well as evidence-based approach to treatment. As a guide through the discussion of the available evidence, a clinical case of hyponatremia associated with CHF is presented. For this case, the severe neurological signs at presentation justified an emergency treatment with hypertonic saline plus furosemide, as indicated. Subsequently, as the neurological emergency began to subside, the reversion of the trend toward hyponatremia overcorrection was realized by continuous infusion of hypotonic solutions, and administration of desmopressin, so as to prevent the very feared risk of an osmotic demyelination syndrome. This very disabling complication of the hyponatremia correction is then briefly outlined. Moreover, the possible advantages related to systematic correction of the hyponatremia that occurs in the course of CHF are mentioned. Additionally, the case of tolvaptan, a vasopressin receptor antagonist, is concisely presented in order to underline the different views that have led to different norms in Europe with respect to the USA or Japan as regards the use of this drug as a therapeutic resource against the hyponatremia

Vasopressin Receptor Antagonists for the Correction of Hyponatremia in Chronic Heart Failure: An Underutilized Therapeutic Option in Current Clinical Practice?

In the congestive heart failure (CHF) setting, chronic hyponatremia is very common. The present review aims at addressing topics relevant to the pathophysiology of hyponatremia in the course of CHF as well as its optimal treatment, including the main advantages and the limitations resulting from the use of the available dietary and pharmacological measures approved for the treatment of this electrolytic trouble. A narrative review is carried out in order to represent the main modalities of therapy for chronic hyponatremia that frequently complicates CHF. The limits of usual therapies implemented for CHF-related chronic hyponatremia are outlined, while an original analysis of the main advancements achieved with the use of vasopressin receptor antagonists (VRAs) is also executed. The European regulatory restrictions that currently limit the use of VRAs in the management of CHF are substantially caused by financial concerns, i.e., the high costs of VRA therapy. A thoughtful reworking of current restrictions would be warranted in order to enable VRAs to be usefully associated to loop diuretics for decongestive treatment of CHF patients with hyponatremia

Effects of Hyponatremia Normalization on the Short-Term Mortality and Rehospitalizations in Patients with Recent Acute Decompensated Heart Failure: A Retrospective Study

Background: Several studies have shown that hyponatremia is associated with increased risk of rehospitalization and death in patients with heart failure. In these studies, chronic heart failure (CHF) patients with persistent hyponatremia were compared only with CHF patients with a normal sodium level at hospital admission. Aims: In the present retrospective study, conducted in a cohort of patients with recent acute decompensated heart failure (ADHF), all with hyponatremia ascertained at the time of hospital admission, we aimed to evaluate the effect of the normalization of serum sodium on the composite endpoint of short-term rehospitalization and mortality. Methods: A retrospective study centered on medical records of patients hospitalized for ADHF in the period April 2013 to April 2016 was performed. Data regarding serum sodium measurements had to be collected from medical records of cardiology wards of two hospitals, and were then processed for statistical analysis. As an inclusion criterion for enrollment, patients had to be suffering from heart failure that had required at least one hospitalization. Moreover, they had to be suffering from a state of hyponatremia (serum sodium < 135 mEq/L) at admission on the occasion of the index hospitalization. Patients with hyponatremia at admission were divided into two groups, one comprising patients with hyponatremia that persisted at the time of discharge (persistent hyponatremia) and a second including patients who had achieved normalization of their serum sodium levels (serum Na+ ≥ 135 mEq/L) during hospitalization until discharge. For both groups, the risk of mortality and rehospitalization during a 30-day follow-up was assessed. Results: One hundred and sixty CHF patients with various degrees of functional impairment were enrolled in the study. Among them, 56 (35%) had persistent hyponatremia over the course of hospitalization. At multivariable Cox proportional-hazards regression analysis, the risk of having a 30-day unplanned readmission or death was significantly higher in patients with persistent hyponatremia compared to those who exhibited a sodium level normalized at discharge (adjusted hazard ratio = 3.0743; 95% CI: 1.3981–6.7601; p = 0.0054). Among the other variables included in the Cox regression model, the number of admissions in the last 12 months (p < 0.0001), the length of stay of the index admission (p = 0.0015) and the New York Heart Association (NYHA) class III at discharge (p = 0.0022) were also identified as risk factors associated with the composite endpoint of 30-day unplanned readmission or death. Conclusions: In the present retrospective study, the risk of 30-day rehospitalization or death was significantly higher in patients with recent ADHF and persistent hyponatremia in comparison with ADHF patients who had had their serum sodium normalized during the hospital stay. This association seemed to be independent of the heart failure severity

Inferior vena cava and hemodynamic congestion

Background: Among the indices able to replace invasive central venous pressure (CVP) measurement for patients with acute decompensated heart failure (ADHF) the diameters of the inferior vena cava (IVC) and their respiratory fluctuationsj so-called IVC collapsibility index (IVCCI) measured by echocardiography, have recently gained ground as a quite reliable proxy of CVP. Objectives: The aims of our study were to compare three different ways of evaluating cardiac overload by using the IVC diameters and/or respiratory fluctuations and by calculating the inter-method agreement Patients and Methods: Medical records of patients hospitalized for right or bi-ventricular acute decompensated heart failure from January to December 2013 were retrospectively evaluated. The predictive significance of the IVC expiratory diameter and IVC collapsibility index (IVCCI) was analyzed using three different methodsj namely a) the criteria for the indirect estimate of right atrial pressure by Rudski et al. (J Am Soc Echocardiogr. 2010); b) the categorization into three IVCCI classes by Stawicki et al. (J Am Coll Surg. 2009); and c) the subdivision based on the value of the maximum IVC diameter by Pellicori et al. (JACC Cardiovasc Imaging. 2013). Results: Among forty-seven enrolled patientsj those classified as affected by persistent congestion were 22 (46.8%) using Rudski’s criteria1 or 16 (34%) using Stawicki’s criteriaj or 13 (27.6%) using Pellicori’s criteria. The inter-rater agreement was rather poor by comparing Rudski’s criteria with those of Stawicki (Cohen’s kappa = 0.369; 95% CI 0.197 to 0.54) as well as by comparing Rudski’s criteria with those of Pellicori (Cohen’s kappa = 0.299; 95% CI 0.135 to 0.462). Further a substantially unsatisfactory concordance was also found for Stawicki’s criteria compared to those of Pellicori (Cohen’s kappa= 0.468; 95% CI 0.187 to 0.75). Conclusions: The abovementioned IVC ultrasonographic criteria for hemodynamic congestion appear clearly inconsistent. Alternatively, a sequential or simultaneous combination of clinical scores of congestion IVC ultrasonographic indicesj and circulating levels of natriuretic peptides could be warranted

A Case of Fatal Intestinal Infarct Preceded by Recurrent Ischaemic Colitis due to the Enterotoxic Effect of Sodium Polystyrene Sulfonate

Case description: A 64-year-old patient with chronic renal failure and persistent hyperkalaemia not corrected by dialysis, was prescribed sodium polystyrene sulfonate (SPS) at a low dose (30 g/day for 2 days a week during the long interdialytic interval). After 3 months of therapy, the patient developed intense abdominal pain with non-specific colitis identified with a colonoscopy. In addition, the biopsy specimens showed rhomboid SPS crystals in the intestinal mucosa. Fourteen months after discontinuing therapy, the patient again presented with colitis and persistent biopsy finding of SPS crystals. The patient died a few months later due to intestinal infarction. Discussion and conclusion: SPS is a cation exchange resin used to treat hyperkalaemia resistant to dialysis, but may cause inflammation and ischaemia of the colon. In our patient, a short 3-month course of low-dose SPS therapy (without sorbitol, which is used to counter iatrogenic constipation caused by SPS) induced relapsing colitis, which was followed by massive intestinal infarction a few months later. In light of frequent reports of its enterotoxic effects, SPS should be replaced with the new potassium chelators (patiromer and sodium zirconium cyclosilicate)

Two different methods of determining B-type natriuretic peptide, either from fingertip’s capillary blood or antecubital vein; A comparison regarding diagnostic accuracy in patients with chronic heart failure in NYHA class I-III

Background: In recent years, several systems have been implemented to achieve quick and non-invasive measurements of B-type natriuretic peptide (BNP). Among them, Alere™ heart check (AHC) BNP test represents the most recent advancement. It is a rapid point of care immunoassay (POC), projected for measuring BNP directly from a capillary whole blood sample. Objectives: This study aimed to compare analytical and clinical performances of this new POC to our reference method (Abbott architect system). Patients and Methods: 111 patients with stable chronic heart failure (CHF) referred to two cardiac rehabilitation centers were en- rolled from December 2013 to January 2015. These patients were subjected to a simultaneous capillary (AHC) and plasma (Abbott) BNP measurements. Clinical and analytical performance of AHC were assessed and compared to the reference method. Results: Capillary BNP showed a good correlation with the reference method (r = 0.94, P < 0.0001), although the values diverged when BNP was higher than 1500 pg /mL. Indeed, the AHC had a relatively poor precision and the coefficient of variability was 10.1% and 18% for low and high controls, respectively. However, both methods showed similar diagnostic performances in discriminating patients with heart failure in NYHA class I from those belonging to NYHA classes II-III, with values of area under the curve (AUC) of 0.983 and 0.984, respectively, and equivalent sensitivity, specificity and positive and negative likelihood ratios. Conclusions: The AHC BNP test is a good POC able to provide reliable information about hemodynamic status of CHF patients, especially of those belonging to NYHA classes I-III

Platypnea–Orthodeoxia Syndrome: Multiple Pathophysiological Interpretations of a Clinical Picture Primarily Consisting of Orthostatic Dyspnea

Platypnea–orthodexia syndrome (POS) is often a challenging diagnostic problem. It is characterized by dyspnea that is accentuated by standing or sitting positions due to a marked fall in blood oxygen saturation, and instead is improved by assuming the lying position. In the present brief review, the authors address the pathophysiology of POS, and outline its clinical symptoms as well as the main modalities of diagnostic evaluation and possible therapeutic options. Moreover, some problems concerning much-debated issues and persistent uncertainties about the pathophysiology of POS are presented along with the description of the diagnostic and therapeutic resources currently available for this syndrome