Background—: Abnormalities in cardiac structure and function in heart failure with preserved ejection fraction may help identify patients at particularly high risk for cardiovascular morbidity and mortality. Methods and Results—: Cardiac structure and function were assessed by echocardiography in a blinded core laboratory at baseline in 935 patients with heart failure with preserved ejection fraction (left ventricular ejection fraction ≥45%) enrolled in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial and related to the primary composite outcome of cardiovascular death, heart failure hospitalization, or aborted cardiac arrest, and its components. At a median follow-up of 2.9 years, 244 patients experienced the primary outcome. Left ventricular hypertrophy (adjusted hazard ratio, 1.52; 95% confidence interval, 1.16–2.00), elevated left ventricular filling pressure (E/E′; adjusted hazard ratio 1.05 per 1 integer increase; 95% confidence interval, 1.02–1.07), and higher pulmonary artery pressure assessed by the tricuspid regurgitation velocity (hazard ratio, 1.23 per 0.5 m/s increase; 95% confidence interval, 1.02–1.49) were associated with the composite outcome and heart failure hospitalization alone after adjusting for clinical and laboratory variables. The risk of adverse outcome associated with left ventricular hypertrophy was additive to the risk associated with elevated E/E′. Conclusions—: Among heart failure with preserved ejection fraction patients enrolled in TOPCAT, left ventricular hypertrophy, higher left ventricular filling pressure, and higher pulmonary artery pressure were predictive of heart failure hospitalization, cardiovascular death, or aborted cardiac arrest independent of clinical and laboratory predictors. These features, both alone and in combination, identify heart failure with preserved ejection fraction patients at particularly high risk for cardiovascular morbidity and mortality. Clinical Trial Registration—: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00094302.

Adverse cardiac remodeling leads to impaired ventricular function and heart failure, remaining a major cause of mortality and morbidity in patients with acute myocardial infarction. It have been shown that, even if all the recommended therapies for ST-segment elevation myocardial infarction are performed, one third of patients undergoes progressive cardiac remodeling that represents morphological basis for following heart failure. The need to extend our knowledge about factors leading to different clinical scenarios of myocardial infarction and following complications has resulted in a research of immuno-inflammatory pathways and molecular activities as the basis for post-infarction remodeling. Recently, macrophages (cells of the innate immune system) have become a subject of scientific interest under both normal and pathological conditions. Macrophages, besides their role in host protection and tissue homeostasis, play an important role in pathophysiological processes induced by myocardial infarction. In this article we summarize data about the function of monocytes and macrophages plasticity in myocardial infarction and outline potential role of these cells as effective targets to control processes of inflammation, cardiac remodeling and healing following acute coronary event.

The hospital mortality in patients with ST-segment elevation myocardial infarction (STEMI) is about 6% and has not decreased in recent years. The leading cause of death of these patients is ischemia/reperfusion (I/R) cardiac injury. It is quite obvious that there is an urgent need to create new drugs for the treatment of STEMI based on knowledge about the pathogenesis of I/R cardiac injury, in particular, based on knowledge about the molecular mechanism of ferroptosis. In this study, it was demonstrated that ferroptosis is involved in the development of I/R cardiac injury, antitumor drug-induced cardiomyopathy, diabetic cardiomyopathy, septic cardiomyopathy, and inflammation. There is indirect evidence that ferroptosis participates in stress-induced cardiac injury. The activation of AMPK, PKC, ERK1/2, PI3K, and Akt prevents myocardial ferroptosis. The inhibition of HO-1 alleviates myocardial ferroptosis. The roles of GSK-3β and NOS in the regulation of ferroptosis require further study. The stimulation of Nrf2, STAT3 prevents ferroptosis. The activation of TLR4 and NF-κB promotes ferroptosis of cardiomyocytes. MiR-450b-5p and miR-210-3p can increase the tolerance of cardiomyocytes to hypoxia/reoxygenation through the inhibition of ferroptosis. Circ_0091761 RNA, miR-214-3p, miR-199a-5p, miR-208a/b, miR-375-3p, miR-26b-5p and miR-15a-5p can aggravate myocardial ferroptosis.

Cardiogenic shock (CS) is one of the most serious complications of myocardial infarction (MI) with a high mortality rate. The timely and effective prevention and early suppression of this adverse event may influence the prognosis and outcome in patients with MI complicated by CS (MI CS). Despite the use of existing pharmaco-invasive options for maintaining an optimal pumping function of the heart in patients with MI CS, its mortality remains high, prompting the search for new approaches to pathogenetic therapy. This review considers the role of the systemic inflammatory response in the pathogenesis of MI CS. The primary processes involved in its initiation are described, including the progression from the onset of MI to the generalization of the inflammatory response and the development of multiple organ dysfunction. The approaches to anti-inflammatory therapy in patients with CS are discussed, and further promising research directions are outlined. In this review, we updated and summarized information on the inflammatory component of MI CS pathogenesis with a particular focus on its foundational aspects. This will facilitate the identification of specific inflammatory phenotypes and endotypes in MI CS and the development of targeted therapeutic strategies for this MI complication.

To assess the dynamics of serum levels of soluble isoform of suppression of tumorigenicity 2 (sST2) and N-terminal pro-brain natriuretic peptide (NT-proBNP) and their correlations with the development of adverse left ventricular remodeling (LVR) through 6 months in patients with primary myocardial infarction with ST-segment elevation (STEMI). Subjects were 31 patients with STEMI (median age: 58 years), who underwent percutaneous coronary intervention (PCI) during the first 24 hours of the onset of myocardial infarction (MI). Blood samples and parameters of echocardiography were assessed at days 1, 3, 7, and 14 and 6 months after STEMI. Serum levels of sST2 and NT-proBNP decreased during the 6-month period. Levels of sST2 decreased by 48% from admission to day 7, and levels of NT-proBNP decreased by 40% from day 7 to 6 months after STEMI. Serum levels of sST2 at day 1 (r = 0.5, P < .05) and day 3 (r = 0.4, P < .05) were associated with adverse LVR by 6 months after STEMI. Logistic regression analysis showed that a high concentration of sST2 at day 7 increased the risk of adverse LVR (95% confidence interval [CI], 0.5-0.9; areas under curve [AUC] = 0.8; P = .002), with 92% sensitivity and 70% specificity. A multivariate analysis model revealed that adverse LVR was associated with the level of sST2 (P = .003) and with complete revascularization (P = .01) at the admission. The dynamics of serum levels of sST2 and NT-proBNP were different. The level of sST2 normalized by the 7th day; NT-proBNP decreased only by the end of the 6-month period after MI. Increased serum levels of sST2 by the 7th day of MI were associated with the development of adverse LVR by the end of the 6-month period.