Cardiogenic shock; focus on ventilatory strategies, the elderly, and biomarker-based risk stratification

Cardiogenic shock (CS) is the most severe form of acute heart failure (HF) characterized by hypotension and systemic hypoperfusion caused by cardiac dysfunction. Prolonged hypotension provokes neurohumoral compensatory mechanisms and systemic inflammatory responses, leading to organ injury followed by multiorgan failure and poor prognosis. CS may be caused by various etiological factors, acute coronary syndromes (ACS) being the most common cause. In addition to prompt recognition of CS, the cause of shock should be treated urgently, as by means of immediate revascularization in the case of ACS-related CS. Although aggressive therapy options, such as mechanical circulatory devices and ventilatory support, may be used, this approach is demanding on the patient, carries risk for complications, and requires additional healthcare resources. Despite advanced therapy options, prognosis in CS is still very poor with a short-term mortality rate up to 40%. Appropriate risk assessment in the early stage of shock is crucial to identify patients most likely to benefit from intensive and costly treatment. The aim of this thesis was to assess the treatment of respiratory failure in CS, focusing on the use of different ventilatory strategies and their impact on outcome; to evaluate the contemporary clinical picture, prognosis, and risk assessment of elderly (≥ 75 years) CS patients; and to investigate prognostic properties of two novel biomarkers in the early phase of CS. The study population consisted of the multinational, observational, prospective CardShock study, which included 219 patients with both ACS and non-ACS etiologies. Study I evaluated the use of different ventilatory strategies in CS. Although most patients (63%) were treated with invasive mechanical ventilation (IMV), a fair number were successfully treated with non-invasive ventilation (NIV) (12%). The intensity of respiratory support required was dependent on the severity of shock; those treated with IMV suffered from more severe shock and had higher 90-day mortality compared with those treated with NIV (49% vs. 27%). However, after balancing the IMV and NIV groups with shock severity and clinical characteristics, the choice of ventilatory strategy itself did not influence the outcome. Study II assessed the key features of elderly (≥ 75 years) CS patients. The elderly constituted a quarter of the population. Despite similar etiology and treatment of shock, they had a higher in-hospital mortality rate compared with younger patients (46% vs. 33%). However, those elderly patients who survived to hospital discharge had a prognosis comparable to that of the younger. The two contemporary risk prediction scores, the CardShock risk score and the IABP-SHOCK II risk score, proved to be useful in the early risk stratification in the elderly patients as well. Furthermore, by incorporating the novel biomarkers into the scores, the risk prediction ability of the scores improved markedly. Study III evaluated concentrations of a novel biomarker, growth differentiation factor 15 (GDF-15), in CS. GDF-15 is a stress-responsive cytokine that is expressed under acute and chronic stressful conditions and it has shown prognostic potential in various diseases. In this study GDF-15 levels were already very high at the beginning of CS and associated with markers of hypoperfusion (high lactate, low pH) and various acute organ dysfunctions (heart, renal, liver) indicating severe circulatory failure. High and increasing levels of GDF-15 were associated with a worse outcome, while low and decreasing levels were indicative of better prognosis. Furthermore, GDF-15 improved the early risk stratification of CS beyond the clinical risk score. Study IV investigated the levels of soluble urokinase-type plasminogen activator receptor (suPAR) in the early stage of CS. suPAR is a novel biomarker secreted in response to inflammatory stimuli and thought to reflect the level of immunoactivation. suPAR has prognostic ability in many acute and chronic diseases, including cardiovascular diseases, cancer, and sepsis. In this study, suPAR levels were clearly elevated during the first days of CS. High levels were associated with both acute and chronic organ dysfunctions. suPAR had independent prognostic potential in CS and improved the risk stratification, especially in the patients with intermediate risk. In conclusion, NIV can be used safely in the treatment of respiratory failure in suitable CS patients. The choice of ventilation strategy did not appear to influence outcome. Elderly patients constitute a considerable portion of CS patients with high mortality. Contemporary risk scores are also useful for early risk prediction in this age group. High levels of the novel biomarkers GDF-15 and suPAR are indicative of severe circulatory failure and end-organ injury, suggesting poor prognosis. These biomarkers may be new prognostic tools in the risk assessment of CS.

Grantor dc:publisher

Helsingin yliopisto

Year dc:date.issued

2022

Author dc:creator

• Hongisto, Mari

• lääketieteellinen

Statement dc:rights

• Julkaisu on tekijänoikeussäännösten alainen. Teosta voi lukea ja tulostaa henkilökohtaista käyttöä varten. Käyttö kaupallisiin tarkoituksiin on kielletty.
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• Publikationen är skyddad av upphovsrätten. Den får läsas och skrivas ut för personligt bruk. Användning i kommersiellt syfte är förbjuden.

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/10138/343465

OAI record oai:identifier

https://helda.helsinki.fi/server/oai/request?verb=GetRecord&metadataPrefix=dim&identifier=oai%3Ahelda.helsinki.fi%3A10138%2F343465