Cardiovascular, Pulmonary, and Neuropsychiatric Short- and Long-Term Complications of COVID-19.

Beginning with the various strategies of the SARS-CoV-2 virus to invade our bodies and manifest infection, and ending with the recent long COVID, we are witnessing the evolving course of the disease in addition to the pandemic. Given the partially controlled course of the COVID-19 pandemic, the greatest challenge currently lies in managing the short- and long-term complications of COVID-19. We have assembled current knowledge of the broad spectrum of cardiovascular, pulmonary, and neuropsychiatric sequelae following SARS-CoV-2 infection to understand how these clinical manifestations collectively lead to a severe form of the disease. The ultimate goal would be to better understand these complications and find ways to prevent clinical deterioration.

All-Cause Mortality and Trimethylamine N-Oxide Levels in Patients with Cardiovascular Disease.

INTRODUCTION: Trimethylamine N-oxide (TMAO) is an organic compound with a well-established involvement in the pathogenesis of cardiovascular disease (CVD). However, data on the links between TMAO levels and cardiovascular mortality in Polish patients are lacking. OBJECTIVES: We aimed to assess the relationship between serum TMAO levels and 5-year mortality in Polish patients with CVD. PATIENTS AND METHODS: We retrospectively assessed serum TMAO levels in 1,036 consecutive patients (median age, 62 years; men, 61%) hospitalized between 2013 and 2015. Correlations between TMAO levels and 5-year mortality as well as anthropometric and biochemical parameters were assessed for the whole population and the subgroups of patients with acute coronary syndrome, stable coronary syndrome (SCS), chronic heart failure (HF), and atrial fibrillation (AF). RESULTS: In the univariate analysis, increased TMAO levels predicted 5-year mortality without clinically significant power (hazard ratio [HR], 1.01; 95% CI: 1.006-1.018; p < 0.0001). However, even this weak effect was lost in the multivariate analysis after adjustment for age, sex, comorbidities, and laboratory parameters. In the whole study group, TMAO levels in the fourth quartile of concentration (>6.01 µM) predicted 5-year mortality only in the univariate analysis (HR: 1.55; 95% CI: 1.34-1.79; p < 0.0001). In subgroup univariate analysis, TMAO levels predicted 5-year mortality in patients with SCS, chronic HF, and AF. CONCLUSIONS: Despite the promising results of previous studies, our study shows that the level of TMAO has at most moderate value in predicting all-cause mortality. TMAO levels depend on other clinical variables, which limits the use of TMAO as an independent predictor of mortality in these patients.

Citrulline and long-term mortality in patients with cardiovascular disease.

BACKGROUND: Cardiovascular disease (CVD) is associated with intestinal barrier dysfunction and increased intestinal permeability. Increased intestinal permeability to gut microbial metabolites may accelerate the progression of CVD. Plasma citrulline levels are a marker of functional enterocyte mass, and reduced citrulline levels indicate intestinal epithelial damage. Citrulline was reported as a useful prognostic marker in critically ill patients. However, data are lacking on the association of citrulline with long-term mortality in patients with CVD and with the levels of trimethylamine N-oxide (TMAO), a microbiota-derived metabolite which has been implicated in the pathogenesis of CVD. OBJECTIVES: To assess the effect of citrulline levels, a marker of intestinal barrier disruption, on long-term mortality in patients with CVD. Moreover, the relationship between the concentrations of 2 biomarkers - citrulline and TMAO - was assessed. MATERIAL AND METHODS: Serum citrulline levels were retrospectively assessed in 1036 consecutive patients with CVD (median age: 62 years; 61% men) hospitalized between 2013 and 2015. Associations of citrulline levels with 5-year mortality rates as well as anthropometric and biochemical parameters were evaluated for the entire study group and in subgroups of patients with acute coronary syndrome (ACS), chronic coronary syndrome, chronic heart failure (chronic HF), and atrial fibrillation (AF). Correlations between serum citrulline and TMAO levels were assessed. RESULTS: The median citrulline level in the study population was 22.5 µM (interquartile range (IQR): 17.8-27.9). Citrulline levels were not associated with 5-year mortality in patients with CVD (hazard ratio (HR) = 0.99; 95% confidence interval (95% CI): 0.97-1.00; p = 0.49). Median citrulline levels differed significantly between deceased patients and survivors at 5 years in patients with ACS (p = 0.025). There were no significant correlations between citrulline and TMAO levels (Kendall's tau = 0.027). CONCLUSIONS: Decreasing citrulline levels do not predict long-term mortality of hospitalized patients with CVD. Moreover, they are not associated with the serum levels of TMAO in these patients.

Relationships between Circulating Matrix Metalloproteinases, Tissue Inhibitor TIMP-2, and Renal Function in Patients with Myocarditis.

INTRODUCTION: Under physiological conditions, the myocardial extracellular matrix (ECM) is maintained by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). However, changes in the balance between MMPs and TIMPs can lead to pathological remodeling of the ECM, which contributes to cardiovascular and kidney diseases. The aim of our study was to assess levels of MMPs and TIMP-2 in patients with myocarditis and their relationship to renal function. MATERIALS AND METHODS: Forty five patients with myocarditis who underwent CMR were included, comprising 11 with concurrent chronic kidney disease (CKD). Blood samples were obtained to assess serum levels of MMP-2, MMP-3, MMP-9, and TIMP-2. RESULTS: Serum MMP-2, MMP-3, and TIMP-2 levels negatively correlated with the ejection fraction in patients with myocarditis, while MMP-3 levels correlated with longitudinal deformation (p < 0.05). Serum MMP-2, MMP-3, and TIMP-2 levels also negatively correlated with renal function, as assessed by the estimated glomerular filtration rate (eGFR) (p < 0.05). Patients with myocarditis and concurrent CKD had higher levels of MMP-2 and TIMP-2 than those without kidney damage. CONCLUSIONS: (1) We demonstrated that MMP-2, MMP-3, and TIMP-2 concentrations were related to left-ventricular ejection fraction, and MMP-3 levels correlated with longitudinal deformation, indicating MMPs play an important role in the post-inflammatory remodeling of the myocardium. (2) A negative correlation between the eGFR and MMP-2, MMP-3, and TIMP-2 and a positive correlation between creatinine and MMP-3 levels indicate the role of MMPs and TIMP-2 in renal dysfunction.

Platelet Reactivity and Response to Aspirin and Clopidogrel in Patients with Platelet Count Disorders.

BACKGROUND: Platelet reactivity and response to antiplatelet drugs, acetylsalicylic acid (ASA) and clopidogrel, in patients with thrombocytopenia and thrombocythemia can have a potentially important effect on the outcome. The effectiveness and safety of antiplatelet drugs in such patients has not been well examined. Measuring the effect of ASA and clopidogrel on platelets could help guide the therapy. Nevertheless, platelet response to antiplatelet drugs is not routinely measured in platelet count disorders and relevant evidence is scarce. AIMS: The study aimed to measure platelet reactivity and response to ASA and clopidogrel in patients with platelet count disorders. MATERIALS AND METHODS: This was a cross-sectional study of consecutive patients hospitalized in cardiology and hematology departments in the years 2018-2019. The study included patients with thrombocytopenia (PLT < 150 G/L) and thrombocythemia (PLT > 450 G/L) on ASA or dual antiplatelet therapy (DAPT; ASA plus clopidogrel). Controls included patients on antiplatelet drugs with normal platelet count. Platelet reactivity was measured in whole blood (Multiplate aggregometer, Roche, Switzerland) using arachidonic acid (AA), adenosine-5'-diphosphate (ADP), and thrombin receptor agonist peptide-6 (TRAP) as agonists. Platelet aggregation was expressed in arbitrary units (AU). AA-induced aggregation was used as a measure of response to ASA with a cut-off above 30 AU showing high on-treatment platelet reactivity to ASA (HTPR-A). ADP-induced aggregation measured response to clopidogrel with a cut-off above 48 AU for high on-treatment platelet reactivity to clopidogrel (HTPR-C). TRAP-induced aggregation measured baseline platelet reactivity not affected by oral antiplatelet drugs. RESULTS: The study included 174 patients. There were 64 patients with thrombocytopenia, 30 patients with chronic thrombocythemia, and 80 controls. All patients were on 75 mg of ASA and 32% of them additionally on 75 mg of clopidogrel due to a history of recent coronary artery angioplasty. AA- and ADP-induced aggregation was comparable between thrombocytopenic patients and controls (median (IQR) 19 (7-28) vs. 23 (15-38) for AA AU and 32 (16-44) vs. 50 (32-71) for ADP AU, respectively), while it was significantly higher in thrombocythemic patients (median (IQR) 80 (79-118) for AA AU and 124 (89-139) for ADP AU). TRAP-induced aggregation showed significantly lowest aggregation in thrombocytopenic (median (IQR) 41 (34-60) for TRAP AU) and highest in thrombocythemic patients (median (IQR) 137 (120-180) for TRAP AU). HTPR-A was frequent in thrombocythemic patients in comparison with thrombocytopenic patients and controls (60% vs. 4% vs. 15%, respectively; p < 0.0002). HTPR-C was highly common in thrombocythemic patients and least common in thrombocytopenic ones in comparison with controls (80% vs. 8% vs. 40%, respectively; p < 0.001). CONCLUSION: Chronic thrombocytopenia does not significantly affect platelet reactivity and response to ASA and clopidogrel in comparison with controls. Thrombocytosis significantly increases platelet reactivity and attenuates response to both ASA and clopidogrel.

Platelet polyphosphate level is elevated in patients with chronic primary thrombocytopenia: A preliminary study.

BACKGROUND: Platelets are key players in hemostasis. These blood cells contain different types of granules. Recently, there has been a growing interest in the role of inorganic polyphosphate (polyP) structures stored in dense granules of platelets and secreted during platelet activation. OBJECTIVES: To measure platelet polyP levels in patients with thrombocytopenia and thrombocythemia, and to examine the relationship of this indicator with platelet aggregation. MATERIAL AND METHODS: The study included 36 patients with hematological disorders (26 with primary chronic thrombocytopenia and 10 with essential thrombocythemia (ET)) and 40 healthy subjects. Platelet reactivity was measured using whole blood impedance aggregometry. The polyP levels were isolated from lysed platelets, which were obtained from citrated platelet-rich plasma. The procedure included inactivating endogenous phosphatases, removing phosphate units derived from DNA and proteins, and finally hydrolyzing them into monophosphate units. A colorimetric assay using malachite green and ammonium molybdate was performed in order to quantify polyP levels. RESULTS: The polyP concentrations were significantly higher in the patients with thrombocytopenia than in the patients with thrombocythemia or the controls. The polyP level was not correlated with the level of aggregation. CONCLUSIONS: The higher polyP levels observed in the patients with low platelet counts may indicate the existence of a compensatory mechanism that prevents excessive bleeding in such patients. Our study provides evidence of an essential role of polyP in platelet function and the coagulation process.

Response to antiplatelet therapy in patients undergoing invasive treatment due to acute coronary syndrome complicated by cardiogenic shock.

INTRODUCTION: There are limited data on platelet reactivity and response to antiplatelet drugs in patients with cardiogenic shock. AIM: To assess platelet reactivity on dual antiplatelet therapy with acetylsalicylic acid (ASA) and ticagrelor, a novel potent P2Y12 receptor inhibitor, in patients with cardiogenic shock in the course of acute coronary syndrome (ACS) who received invasive treatment. MATERIAL AND METHODS: We enrolled 12 consecutive patients with ACS complicated by cardiogenic shock. To assess response to antiplatelet therapy during cardiogenic shock, only patients with symptoms persisting for at least 3 days and who completed a 5-day follow-up were included in the study. Patients received a loading dose of ASA (300 mg) and ticagrelor (180 mg), followed by a maintenance dose (ASA, 1 × 75 mg; ticagrelor, 2 × 90 mg). Blood samples for platelet function tests were collected. Platelet aggregation was assessed with a Multiplate whole-blood impedance aggregometer. Arachidonic acid (AA), adenosine diphosphate (ADP), and thrombin receptor-activating peptide (TRAP) were used as aggregation agonists. RESULTS: Response to antiplatelet therapy assessed by aggregometry showed numerically higher on-ASA platelet reactivity on day one and statistically significant higher on-ticagrelor platelet reactivity on day one in comparison with following days. There were 2 patients with high on ASA platelet reactivity and 3 with high on ticagrelor platelet reactivity, but only on the day one. CONCLUSIONS: Some patients with cardiogenic shock in the course of ACS treated invasively show a lower response to ASA and ticagrelor only on the first day after invasive treatment, with a good response on subsequent days.

MMP-2 and TIMP-2 in Patients with Heart Failure and Chronic Kidney Disease.

The aim of the study was to assess MMP-2 (matrix metalloproteinase-2) and TIMP-2 (tissue inhibitor of metalloproteinase-2) serum levels in patients with diverse types of heart failure (HF) and chronic kidney disease (CKD). 101 patients with chronic HF were enrolled. Each patient has assessed the serum levels of MMP-2, TIMP-2, and NT-proBNP. Patients were initially classified into 2 groups based on their LVEF. 43 patients were classified into the HFREF group (HF with Reduced Ejection Fraction) and 58 characterized as HFPEF (HF with Preserved Ejection Fraction). Next, all patients were subdivided into 4 groups according to the degree of diastolic dysfunction. 38 patients with CKD were classified into HF/CKD(+) group. The HF/CKD(-) (HF without CKD) group comprised 61 patients. This study provides original data on positive correlation between ejection fraction and MMP-2 levels in all patients with heart failure. Elevated levels of MMP-2 and TIMP-2 were found in serum from patients with chronic kidney disease; in addition, serum levels of MMP-2 were correlated with the degree of kidney failure. In all groups of patients there was positive correlation between MMP-2 and TIMP-2. Among patients with heart failure etiology was not related to MMP-2 and TIMP-2 serum levels.

Characteristics of chaotic processes in electrocardiographically identified ventricular arrhythmia.

BACKGROUND: The theory of chaos proves a deterministic mechanism of induction of multiple complex processes previously thought to be random in nature. This research explains how these complex processes develop. The aim of the study was to test the hypothesis of the chaotic nature of myocardial electrical events during ventricular tachycardia (VT) and ventricular fibrillation (VF). METHODS: Original hardware and software was developed for digitalization of on-line electrocardiography (ECG) data, with the functions of automatic and manual identification as well as categoriza-tion of specific ventricular arrhythmias. Patient ECGs were recorded by specially developed measuring equipment (M2TT). Available ECG sampling frequency was 20,000 Hz, and it was possible to analyze the signal retrospectively. Digital ECG of the sinus rhythm (SR) was analyzed with non-sustained VT, VT and VF. The signals were then subjected to mathematical analysis. Using wavelet analysis, signals carrying frequencies from various ranges were isolated from baseline and each of these isolated signals was subjected to Fourier transformation to check on differences in the Fourier power spectra of the analyzed VT and VF signals. RESULTS: Ventricular tachycardia identified based on ECG fulfills the criteria of a chaotic process, while no such properties were found for SR and VF. Information obtained by the ECG is used to record myo-cardial electrical signals, but they are not sufficient to differentiate between an advanced chaotic state and the process of linear expansion of electrical activation within the myocardium. CONCLUSIONS: Electrophysiological study requires advanced methods to record the signal of myocardial electrical activity, as ECG is not sufficiently sensitive to identify the features of a chaotic process during VF. (Cardiol J 2017; 24, 2: 151-158).

Left main aneurysm and what's next?

The purpose of the case report is to present a case of a 65-year-old male, referred for coronary angiography because of a typical chest pain. The coronary angiography showed an aneurysm of the left main coronary artery. Despite the absence of obvious ischemic symptoms and because of the potential complications of the aneurysm with a width of 15 mm, the patient underwent surgery.