Patient periprocedural stress in cardiovascular medicine: friend or foe?

Abstract

Stress, a disruption of homeostasis, is an unavoidable part of everyday life. In medical procedures, stress profoundly affects both operators and patients. Although the stress reaction has evolved to aid survival of physical trauma, it may also be harmful, by aggravating the baseline medical condition and/or creating new stress-related medical problems. Stress responses comprise several protective mechanisms that are particularly relevant in the clinical setting (e.g., a procoagulatory state and blood loss counteraction, preservation of blood perfusion pressure, prevention of hypoglycemia, enhanced immune response). Beneficial psychological effects prevent recurrence of traumatic memories, and promote patient compliance and positive lifestyle changes. In contrast, overt acute stress responses may lead to severe pathological conditions such as cytokine storm, post-traumatic stress disorder, takotsubo syndrome, deep venous thrombosis and pulmonary embolism, myocardial infarction, life-threatening arrhythmias and sudden cardiac death. There is also evidence that stress exposure may promote atherosclerosis and reduce long-term benefits from the intervention (increase in major adverse clinical events, in-stent restenosis, etc.). Insights into the role of stress on the operator's performance have recently led to the introduction of counteractive measures such as simulation training. Conversely, very little is known about the effect of the patient's periprocedural stress on the outcomes of cardiovascular procedures. Recent data show that the patient periprocedural stress affects the well-being of whole families. This review, focused on topics particularly relevant to cardiovascular interventions, provides a mechanistic insight into beneficial and harmful effects of periprocedural patient stress, including the array of available stress-relieving measures.

Keywords: cardiovascular interventions; effects; management; mechanisms; stress.

Figure 1

Schematic representation of physiologic (A) and pathologic (B) stress responses, explaining the origins of allostatic load and overload. Modified after [1, 52]

Figure 2

The allostatic network and its major regulatory pathways. The stress response is always initiated in the brain, but different stressors elicit distinct pathways of activation, which impacts the resulting net balance of the effectors. The complex of the paraventricular nucleus of the hypothalamus (PVN) is undoubtedly the central integrating point of all of the inputs, which initiates both HPA and SAM axes; however, it is the bed nucleus striae terminalis (BST) and dorsomedial hypothalamus (DMH) that link the major inputs with PVN, and therefore serve as a central management unit of the stress response. The fastest action is mediated via neural pathways of the autonomic nervous system (which seems to be coordinated by the insular cortices [25]) and, within (milli)seconds, reaches effector organs facilitating the fight-or-flight response. However, the subsequent intermediate and slow responses (due to the released co-transmitters) also seem very important for the end effect of activation. The most important transmitters in each branch are indicated in bold. The SAM axis, after the first hit from its nerve endings and reciprocal PNS withdrawal, triggers release and synthesis of new catecholamines in the adrenal medulla, which takes minutes. Even more inertly, the HPA axis takes tenths of minutes to fully enable its action, which can be generally perceived as protective and counteracting the SAM axis (despite many synergistic actions) and in physiologic conditions – in response to a short acting stressor – ultimately leads to waning of catecholamine and inflammatory allostatic load, and terminates the stress response via a negative feedback loop through the hippocampus. Other circulating hormones released from the hypothalamus, pituitary and gonads modulate the whole response in a complex manner 5-HT – 5-hydroxytryptamine (serotonin), A – adrenaline, AT – angiotensin II, NA – noradrenaline, DA – dopamine, AchM and AchN – acetylcholine acting via muscarinic and nicotinic receptors respectively, ACTH – adrenocorticotropic hormone, CRH – corticotrophin releasing hormone, GR – glucocorticoid receptor, MR – mineralocorticoid receptor, NPY – neuropeptide Y, NO – nitric oxide, FSH – follicle-stimulating hormone, GnRH – gonadotropin releasing hormone, LH – luteinizing hormone, SP – substance P, CVO – circumventricular organs (organum vasculosum of the lamina terminalis and subfornical organ). Drawn based on references: [1, 15, 22, 25, 52]

Figure 3

Mechanisms through which stress contributes to contractility impairment in acute coronary syndromes (ACS). Stress-related sympathetic overactivity causes hypercontraction, which results in impaired relaxation, and, if severe, can lead to left ventricular outflow tract obstruction (LVOTO), and to development of contraction-band necrosis (as in takotsubo syndrome). In predisposed individuals (estimated to be one in every 4 patients [4]), sympathetic stimulation can cause neurogenic stunning, and contribute to acute heart failure. Neurogenic stunning can be focal (remote to ischemic insult) or global. Ischemic stunning occurs in the area of impaired perfusion. Hibernation is relatively rare in ACS, but may coexist in chronically and profoundly hypoperfused regions (typically > 85% stenosis), contributing to chronic ischemic heart failure development and to systolic function recovery, if unfrozen by revascularization. According to Iwaszczuk et al. [4] (modified)