Proposal for Heart Failure Progression Based on the ‘Chloride Theory’: Worsening Heart Failure with Increased vs. Non-Increased Serum Chloride Concentration

AIMS: Chloride (Cl) is an established key electrolyte for the activation of the renin-angiotensin-aldosterone system. Recent studies have shown the serum Cl as a key electrolyte for the regulation of body fluid distribution in heart failure (HF) patients. The clinical differences of worsening HF status according to the changes in serum Cl concentration are unclear. METHODS AND RESULTS: Data from 47 chronic HF patients were analysed. Upon worsening HF, each patient exhibited at least two HF-related signs. Blood tests included haemoglobin (Hb), haematocrit (Ht), mean red blood cell volume (MCV), albumin, serum solutes, and b-type natriuretic peptide. The relative change in the plasma volume (%PV) from stable to worsening HF was estimated as follows: 100 × Hb (stable) × 1 - Ht (worse) /Hb (worse) × 1 - Ht (stable) - 100. When patients were divided into two groups based on changes in serum Cl concentration from stable to worsening HF, the pathophysiologic features of the patients with increased Cl (range 1-23 mEq/L; n = 31) included a greater increase in serum sodium (2. 94 ± 4. 15 vs. -0. 69 ± 3. 75 mEq/L, P = 0. 005), higher vascular expansion (12 ± 11. 1 vs. 4. 81 ± 7. 94%, P = 0. 026), a tendency towards a greater MCV (1. 23 ± 2. 36 vs. -0. 06 ± 1. 88 fL, P = 0. 065), and preserved renal function defined by the absence of an increase of serum creatinine (-0. 24 ± 0. 39 vs. -0. 05 ± 0. 12 mg/dL, P = 0. 057) compared to patients with non-increased Cl (range -9 to 0 mEq/L; n = 16). Clinically, the increased Cl group had fewer HF signs (2. 65 ± 0. 71 vs. 3. 31 ± 0. 79, P = 0. 005) although the change in symptoms did not differ between groups (48% vs. 63%, P = 0. 54). CONCLUSIONS: The present study suggests a new clinical entity of worsening HF status, that is, HF with increased vs. non-increased serum Cl concentration from clinical stability to worsening HF.