Difficult cases in heart failure: amiodarone lung injury: another heart failure mimic?

Careful thought must be given to the development of bystander pathology that could mimic worsening of heart failure. Recent trials with patients receiving amiodarone record a low rate of amiodarone pulmonary toxicity of 1.6%. Bronchoalveolar lavage in amiodarone toxicity demonstrates an absolute and relative lymphocytic alveolitis, suggesting hypersensitivity, but this finding is neither sensitive nor specific. Recently, KL-6, a mucin-like high molecular weight glycoprotein secreted by proliferating type II alveolar pneumocytes, has been identified as a potential marker of interstitial pneumonitis. A high index of suspicion combined with rapid exclusion of common confounding mimics can help in establishing the diagnosis of amiodarone lung toxicity.     

Difficult cases in heart failure. Novel diagnostic markers in heart failure: an emerging paradigm shift?

The differential diagnosis of dyspnea can be overwhelming in the presence of competing diseases. The recent advent of the peptide marker brain natriuretic peptide has ushered in an era of refined diagnostic capability in heart failure. We present a clinical scenario to illustrate the usefulness of this new biomarker assay in directing appropriate therapy for heart failure. (c)2001 CHF, Inc.     

What causes sudden death in heart failure?

Patients with heart failure experience a number of changes in the electrical function of the heart that predispose to potentially lethal cardiac arrhythmias. Action potential prolongation, the result of functional downregulation of K currents, and aberrant Ca2+ handling is a recurrent theme. Significant alterations in conduction and activation of a number of initially adaptive but ultimately maladaptive signaling cascades contribute to the generation of a highly arrhythmogenic substrate. We review the changes in active and passive membrane properties, neurohumoral signaling, and genetic determinants that predispose to sudden arrhythmic death in patients with heart failure and highlight the critical unanswered questions that are ripe for future investigation.     

How are cytokines activated in heart failure?

In the dilated and failing heart, elevated LV end-diastolic wall stress causes myocardial expression of cytokines, which directly or indirectly influence LV contractile performance and remodeling [22]. Due to poor diffusion of cytokines into the coronary effluent, the contribution of this myocardial production to the raised plasma levels is probably limited. Raised plasma levels of cytokines in heart failure are therefore more likely the result of extramyocardial production because of altered tissue perfusion and tissue hypoxia possibly modulated by bacterial endotoxin release from the gut.     

Digitalis in heart failure! Still applicable?

Summary In patients with heart failure and atrial fibrillation cardiac glycosides, generally in combination with beta-blockers, are indicated to control ventricular rate. In systolic heart failure and sinus rhythm, however, the use of digitalis continues to be debated. There are special concerns that cardiac glycosides might lead to an increased mortality rate in women. Retrospective analyses, however, do not indicate any sex-based differences in the effectiveness of cardiac glycosides. Beneficial effects of cardiac glycosides in heart failure seem to be related to the attenuation of sympathetic activation and neurohumoral alterations, which is already obtained at low digoxin serum concentrations, while high serum levels are associated with increased mortality. Therefore, in patients with sinus rhythm who remain symptomatic under an optimized therapy with ACE inhibitors, beta-blockers and diuretics in addition to digitalis should be considered regardless of the gender. However, target serum digoxin concentrations should be low in a range of 0.5 to 0.8 ng/ml.     

TNFα in patients with congestive heart failure

Abstract. It is now generally accepted that chronically extensive stimulation of the cytokine system—and of TNF in particular—is detrimental to the heart and to peripheral tissue and that such stimulation may contribute to the pathogenesis of congestive heart failure of various causes. During the past decade, basic and clinical research has provided growing evidence for the role of systemic and local inammatory responses that, however, have so far failed to translate into new treatments for patients. The present paper represents an attempt to critically review the general concepts that lie behind the dichotomy existing between an impressive bulk of biologic research showing the role of TNF as a pathogen in congestive heart failure and the difculties in translating this evidence into patients treatment.     

Can heart rate variation rule out sleep-disordered breathing in heart failure?

In patients with obstructive sleep apnoea (OSA), the very low frequency power spectral density index (VLFI) derived from analysis of heart rate correlates with the severity of obstructive apnoeas. VLFI is also associated with Cheyne-Stokes respiration/central sleep apnoea (CSR/CSA) in congestive heart failure (CHF). The present authors have tested the hypothesis that per cent VLFI, derived from a standard Holter ECG recording, can be used to detect the presence of OSA and CSR/CSA in patients with mild-to-moderate CHF. In total, 60 CHF patients underwent polysomnography with monitoring of heart rate. Data from 33 patients were analysed for per cent VLFI. Of the 60 patients, 27 were excluded due to atrial fibrillation, extensive pacing or frequent ventricular extra systoles. Receiver operator characteristic curves were constructed to establish the per cent VLFI that would optimally identify the presence or absence of sleep-disordered breathing. Using an apnoea-hypopnoea index>20 events.h-1 and setting the per cent VLFI at 2.23% yielded a sensitivity of 85%, specificity of 65%, positive predictive value of 61% and a negative predictive value of 87%. The latter increased to 100% when using an apnoea-hypopnoea cut-off of 30 events.h-1. In conclusion, these results suggest that spectral analysis of heart rate may be useful as a "rule-out test" for sleep-disordered breathing in patients with mild-to-moderate congestive heart failure.     

Pharmacotherapy in congestive heart failure: Do NSAIDs attenuate the therapeutic effect of ACE inhibitors in heart failure patients?

Heart failure (HF) is a disease which is prevalent in the elderly. Concomitant rheumatological diseases are also prevalent in this population which require treatment with NSAIDs. Aspirin is also routinely used for the primary and secondary prevention of coronary artery disease (CAD) which is a common cause of HF. ACE inhibitors are the cornerstone of drug therapy in managing patients with HF. Elderly patients with HF are frequently encountered with multiple drug therapy, such as nonsteroidal antiinflammatory drugs (NSAIDs) including aspirin and ACE inhibitors. In recent years there has been a concern of negative interaction between these two common drug therapies in patients with HF which may subsequently attenuate the beneficial effects of ACE inhibitors. Whereas some studies have shown that the coadministration of NSAIDs including aspirin with ACE inhibitors might diminish the degree of improvement in cardiovascular hemodynamics and adversely affect renal functions, other studies have failed to substantiate this. Furthermore, although potential opposing effects of NSAIDs and ACE inhibitors on prostaglandin synthesis has been cited as the mechanism responsible for the negative interactions, more work is needed in this area to better define the precise reasons responsible for it. However, based on the available data thus far, it is prudent to be aware of such negative interaction and especially in case of aspirin to avoid it by using relatively lower dosage. (c)1999 by CHF, Inc.