Congestive Heart Failure: Where Homeostasis Begets Dyshomeostasis

Abstract

Despite today's standard of care, aimed at containing homeostatic neurohormonal activation, 1 in every 5 patients recently hospitalized with congestive heart failure (CHF) will be readmitted within 30 days of discharge because of a recurrence of their symptoms and signs. In light of recent pathophysiologic insights, it is now propitious to revisit CHF with a view toward complementary and evolving management strategies. CHF is a progressive systemic illness. Its features include: oxidative stress in diverse tissues; an immunostimulatory state with circulating proinflammatory cytokines; a wasting of soft tissues; and a resorption of bone. Its origins are rooted in homeostatic mechanisms gone awry to beget dyshomeostasis. For example, marked excretory losses of Ca 2+ and Mg 2+ accompany renin-angiotensin-aldosterone system (RAAS) activation, causing ionized hypocalcemia and hypomagnesemia that lead to secondary hyperparathyroidism (SHPT) with consequent bone resorption and a propensity to atraumatic fractures. Parathyroid hormone (PTH) accounts for paradoxical intracellular Ca 2+ overloading in diverse tissues and consequent systemic induction of oxidative stress. In cardiac myocytes and mitochondria these events orchestrate opening of the mitochondrial membrane permeability transition pore (mPTP) with an ensuing osmotic-based destruction of these organelles and resultant cardiomyocyte necrosis with myocardial scarring. Contemporaneous with Ca 2+ and Mg 2+ dyshomeostasis is hypozincemia and hyposelenemia, which compromise metalloenzyme-based antioxidant defenses while hypovitaminosis D threatens Ca 2+ stores needed to prevent SHPT. An intrinsically coupled dyshomeostasis of intracellular Ca 2+ and Zn 2+ , representing prooxidant and antioxidant, respectively, is integral to regulating mitochondrial redox state; it can be uncoupled by a Zn 2+ supplement in favor of antioxidant defenses. Hence, the complementary use of nutriceuticals to nullify dyshomeostatic responses involving macro-and micronutrients should be considered. Evolving strategies with mitochondria-targeted interventions interfering with their uptake of Ca 2+ or serving as selective antioxidant or mPTP inhibitor may also prove efficacious in the overall management of CHF.

Bone involvement in aldosteronism

“…The recovery of hypercalciuria and hyperparathyroidism after treatment of PA patients further supports our interpretation. Kamalov and colleagues (19) suggested that hypercalciuria of aldosteronism was related to an expanded extravascular fluid volume resulting in decreased proximal tubular resorption of Na þ and Ca þþ , with consequent increase of their distal delivery. Because aldosterone promotes distal resorption of Na þ but not of Ca þþ , the net effect would be an increase in renal Ca þþ excretion.…”

Correlations between serum intact parathyroid hormone (PTH) and N-terminal-probrain natriuretic peptide levels in elderly patients with chronic heart failure (CHF)

“…Elevated PTH maintains the level of extracellular ionized calcium, resulting in intracellular calcium overload, which is considered a calcium paradox. Intracellular calcium overload leads to myocardial remodeling and reactive oxygen and nitrogen free radicals, overwhelming the antioxidant defense system of the body and promoting the release of inflammatory cytokines such as interleukin-6 and tumor necrosis factor alpha (Grey et al, 1996;Kamalov, Bhattacharya, & Weber, 2010). In this sense, secondary hyperparathyroidism is a systemic illness (Alsafwah et al, 2007;Altay & Colkesen, 2013) responsible for osteopenia and osteoporosis as well as apoptosis of the myocardium and skeletal muscle, which affect various tissues.…”

Alterations of Serum Parathormone, Calcium, and Vitamin D Levels in End-Stage Heart Failure Cases Performed with Left Ventricular Assist Device Implantation

“…Son dönem kalp yetmezliği (SDKY) olgularında, bozulan böbrek fonksiyonlarına ikincil vitamin D eksikliği, hipokalsemi ve bunlara bağlı gelişen sekonder hiperparatiroidizm, kemikteki osteoklastik aktivitede artış ve osteoblastik aktivitede azalma ile sonuçlanmaktadır (1,2). Ayrıca SDKY'ye bağlı gelişen böbrek fonksiyon bozukluğu ve glomerüler filtrasyon hızı (GFH) düşüklüğü ile uzun süreli lup diüretiklerinin kullanımına bağlı böbreklerden kalsiyum reabsorbsiyonu engellenmekte ve hipokalsemi derinleştirebilmektedir.…”