Recainam, A potent new antiarrhythmic agent: Effects on complex ventricular arrhythmias

The antiarrhythmic efficacy and safety of intravenous recainam, a newly synthesized compound displaying potent class I antiarrhythmic activity, were tested in 10 hospitalized patients with frequent (>30/h) complex ventricular ectopic beats. There were seven men and three women of average age 57 years (range 21 to 74); five had ischemic heart disease, three had cardiomyopathy and two had valvular heart disease. Recainam was given as a 3.0 mg/kg per 40 min loading infusion followed by a 0.9 mg/kg per h maintenance infusion over a 24 hour observation period. Arrhythmia response was assessed both in the short term (comparing 2 hours before and 1 hour after drug loading) and in the long term (comparing 48 hours before drug loading and 23 hours of maintenance infusion).The median frequency of total premature ventricular complexes decreased in the short term by 99.6% (from 392.5 to 1.5/h, p < 0.005) and in the long term by 99.7% (from 435 to 1.3/h, p < 0.01). Repetitive beats were suppressed by a median of 100% both in the short term (p < 0.006) and during 24 hour infusion (from 80.9 to 0/h, p < 0.003). More than 90% suppression of repetitive beats occurred in all 10 patients (100%) and more than 90% suppression of total arrhythmias occurred in 9 patients (90%) during the maintenance period. Electrocardiographic PR and QRS intervals increased by 19% (p < 0.001) and 24% (p < 0.003), respectively, during therapy, but the JTc interval decreased (p < 0.001). Plasma recainam concentrations averaged 5.2 ± 0.9 μg/ml after loading and 3.0 ± 0.5 μg/ml during maintenance therapy. No adverse symptoms occurred.In summary, recainam is a promising, highly efficacious and well tolerated agent when administered intravenously for short-term and maintenance suppression of complex ventricular arrhythmias. The efficacy of oral and intravenous recainam for arrhythmia management deserves further evaluation

Etiology of Anemia in Patients With Advanced Heart Failure

ObjectivesWe prospectively investigated the causes of anemia in patients with advanced congestive heart failure (CHF).BackgroundAnemia is common in patients with advanced CHF, and its etiology is generally considered to be multifactorial. However, despite its importance, precise information is lacking regarding the prevalence of putative etiologic factors.MethodsPatients who were hospitalized for decompensated advanced CHF and who were stabilized after their initial treatment underwent evaluation of “clinically significant” anemia, defined as a hemoglobin content <12 g/dl for men and <11.5 g/dl for women. Patients with a serum creatinine concentration >3 mg/dl or patients with concurrent diseases that are known to cause anemia were not included. The initial evaluation included measurements of vitamin B12, folic acid, thyroid-stimulating hormone, erythropoietin, lactate dehydrogenase, Coombs test, multiple fecal occult tests, and bone marrow aspiration. Patients without diagnosis by these methods underwent red cell mass measurement with 51Cr assay.ResultsThe mean age of the 37 patients was 57.9 ± 10.9 years and mean left ventricular ejection fraction 22.5 ± 5.9%. Iron deficiency anemia was confirmed by bone marrow aspiration in 27 patients (73%), 2 patients (5.4%) had dilutional anemia, and 1 patient (2.7%) had drug-induced anemia. No specific cause was identified in 7 patients (18.9%) who were considered to have “anemia of chronic disease.” Serum ferritin for the iron-deficient patients was not a reliable marker of iron deficiency in this population.ConclusionsIn this group of patients, iron deficiency was the most common cause of anemia. The iron status of patients with end-stage chronic CHF should be thoroughly evaluated and corrected before considering other therapeutic interventions

Intermittent Inotropic Infusions Combined With Prophylactic Oral Amiodarone for Patients With Decompensated End-stage Heart Failure

Background: Concern has been raised regarding the mortality and ethics related to the treatment of patients with end-stage chronic heart Failure with chronic intermittent intravenous inotropic agents. We examined whether intermittent inotropic agents combined with oral amiodarone to prevent the proarrhythmic effect of inotropic agents results in better outcomes. Methods: The study included 162 patients with decompensated end-stage chronic heart failure, who could be weaned from an initial 72-hour infusion of intravenous inotropes. Group 1 included 140 patients, who entered a 6-month program of weekly intermittent intravenous inotropic agents plus oral amiodarone, 200 mg twice a day. Group 2 included 22 patients, who were treated with optimal conventional therapy and were hospitalized for administration of intravenous medications as needed. Results: The baseline characteristics of groups I versus 2, including New York Heart Association functional class (IV in both groups), admission systolic arterial blood pressure (99 14 vs. 97 13 mm Hg), right atrial pressure (13 +/- 6 vs. 14 +/- 6 mm Hg), pulmonary capillary wedge rircssure (28 +/- 7 vs, 31 10 mm Hg), serum sodium (136 +/- 7 vs. 139 +/- 6 mEq/L) and scrum creatinine (1.7 +/- 0.8 vs. 1.8 +/- 1.8 mg/dL.), wen., similar. The 6-month (51% vs. 18%) and 1-year (36% VS. 9%) survival rates were significantly higher (P = 0.001 for both) in group 1 than in group 2. In addition, patients treated with intermittent intravenous inotropic agents improved their functional and hemodynamic status. Conclusions: intermittent intravenous inotropic agents combined with prophylactic oral amiodarone seem to improve the outcomes of patients with end-stage chronic heart failure. Further research is warranted to elucidate whether this treatment strategy should be considered as a standard therapy in patients with refractory end-stage heart failure

Outpatient management of chronic heart failure

Introduction: Heart failure (HF) treatment attracts a share of intensive research because of its poor HF prognosis. In the past decades, the prognosis of HF has improved considerably, mainly as a consequence of the progress that has been made in the pharmacological management of HF. Areas covered: This article reviews the outpatient pharmacological management of chronic HF due to left ventricular systolic dysfunction and offers recommendations on the use of various drugs. In addition, the present article attempts to provide practical therapeutic algorithms based on current clinical strategies. Expert opinion: Continued research directed toward identifying factors associated with high pharmacotherapy guideline adherence and understanding of variants that influence response to drugs will hopefully halt or reverse the major pathophysiological mechanisms involved in this syndrome

Innate heart regeneration: endogenous cellular sources and exogenous therapeutic amplification

Introduction: The -once viewed as heretical- concept of the adult mammalian heart as a dynamic organ capable of endogenous regeneration has recently gained traction. However, estimated rates of myocyte turnover vary wildly and the underlying mechanisms of cardiac plasticity remain controversial. It is still unclear whether the adult mammalian heart gives birth to new myocytes through proliferation of resident myocytes, through cardiomyogenic differentiation of endogenous progenitors or through both mechanisms.Areas covered: In this review, the authors discuss the cellular origins of postnatal mammalian cardiomyogenesis and touch upon therapeutic strategies that could potentially amplify innate cardiac regeneration.Expert opinion: The adult mammalian heart harbors a limited but detectable capacity for spontaneous endogenous regeneration. During normal aging, proliferation of pre-existing cardiomyocytes is the dominant mechanism for generation of new cardiomyocytes. Following myocardial injury, myocyte proliferation increases modestly, but differentiation of endogenous progenitor cells appears to also contribute to cardiomyogenesis (although agreement on the latter point is not universal). Since cardiomyocyte deficiency underlies almost all types of heart disease, development of therapeutic strategies that amplify endogenous regeneration to a clinically-meaningful degree is of utmost importance

Reverse remodeling during long-term mechanical unloading of the left ventricle

A significant proportion of patients placed on long-term mechanical circulatory support for end-stage heart failure can be weaned from mechanical assistance after functional recovery of their native heart (”bridge to recovery”). The pathophysiological mechanisms implicated in reverse remodeling that cause a sustained functional myocardial recovery have recently become the subject of intensive research, expected to provide information with a view to accurately identify reliable prognostic indicators of recovery. In addition, this kind of information will enable changes in the strategy of myocardial recovery by modifying the duration and scale of the unloading regimen or by combining it with other treatments that promote reverse remodeling. (c) 2007 Elsevier Inc. All rights reserved

Comparison of three different regimens of intermittent inotrope infusions for end stage heart failure

Aims: Inotrope treatment is often necessary in refractory to optimal management end stage heart failure, when signs of end-organ hypoperfusion appear. The effect of specific inotropes on patient outcome remains controversial. The aim of the study was to compare the effect of levosimendan versus dobutamine, alone or in combination with levosimendan, on the outcome of end-stage heart failure patients, requiring inotropic therapy. Methods and results: We studied 63 patients in NYHA class IV, refractory to optimal medical therapy, recently hospitalized for cardiac decompensation and stabilized by an intravenous inotrope. They were randomly assigned to intermittent infusions of either a) dobutamine, 10 mg/kg/min, versus b) levosimendan, 0.3 mg/kg/min, versus c) dobutamine, 10mg/kg/min + levosimendan 0.2 mg/kg/min, each administered weekly, for 6 h, over a 6-month period. All patients received amiodarone, 400 mg/day, to suppress the proarrhythmic effects of the inotropes. Baseline characteristics of the 3 groups were similar. At 6 months, survival free from death or urgent left ventricular device implantation was 80% in the levosimendan, 48% in the dobutamine (P = 0.037 versus levosimendan), and 43% in the levosimendan + dobutamine (P = 0.009 versus levosimendan) group. At 3 months, NYHA class improved significantly in all 3 groups, whereas pulmonary capillary wedge pressure decreased (27 +/- 4 to 19 +/- 8 mmHg, P = 0.008) and cardiac index increased (1.5 +/- 0.3 to 2.1 +/- 0.3 l/min/m(2), P = 0.002) significantly only in patients assigned to levosimendan. Conclusions: In patients with refractory end-stage heart failure, intermittent administration of levosimendan conferred survival and hemodynamic benefits in comparison to a regimen of intermittent infusions of dobutamine, alone or in combination with levosimendan. (c) 2011 Elsevier Ireland Ltd. All rights reserved