Iron Status and Short-Term Recovery after Non-Severe Acute Myocarditis: A Prospective Observational Study.

Pathomechanisms responsible for recovery from acute myocarditis (MCD) or progression to non-ischemic cardiomyopathy have not been comprehensively investigated. Iron, positioned at the crossroads of inflammation and the energy metabolism of cardiomyocytes, may contribute to the pathophysiology of inflammatory myocardial disease. The aim of this study was to evaluate whether systemic iron parameters are related to myocardial dysfunction in MCD patients. We prospectively enrolled 42 consecutive patients hospitalized for MCD. Their iron status and their clinical, laboratory, and echocardiographic indices were assessed during hospitalization and during ambulatory visits six weeks after discharge. A control group comprising healthy volunteers was recruited. The MCD patients had higher serum ferritin and hepcidin and lower serum iron concentration and transferrin saturation (TSAT) than the healthy controls (all p < 0.01). Six weeks after discharge, the iron status of the MCD patients was already comparable to that of the control group. During hospitalization, lower serum iron and TSAT correlated with higher NT-proBNP (both p < 0.05). In-hospital lower serum iron and TSAT correlated with both a lower left ventricular ejection fraction (LVEF) and worse left ventricular global longitudinal strain at follow-up visits (all p < 0.05). In conclusion, in patients with acute MCD, iron status is altered and normalizes within six weeks. Low serum iron and TSAT are related to greater in-hospital neurohormonal activation and subtle persistent left ventricular dysfunction.

Iron Deficiency and Deranged Myocardial Energetics in Heart Failure.

Among different pathomechanisms involved in the development of heart failure, adverse metabolic myocardial remodeling closely related to ineffective energy production, constitutes the fundamental feature of the disease and translates into further progression of both cardiac dysfunction and maladaptations occurring within other organs. Being the component of key enzymatic machineries, iron plays a vital role in energy generation and utilization, hence the interest in whether, by correcting systemic and/or cellular deficiency of this micronutrient, we can influence the energetic efficiency of tissues, including the heart. In this review we summarize current knowledge on disturbed energy metabolism in failing hearts as well as we analyze experimental evidence linking iron deficiency with deranged myocardial energetics.

The Usefulness of the COVID-GRAM Score in Predicting the Outcomes of Study Population with COVID-19.

BACKGROUND: The COVID-GRAM is a clinical risk rating score for predicting the prognosis of hospitalized COVID-19 infected patients. AIM: Our study aimed to evaluate the use of the COVID-GRAM score in patients with COVID-19 based on the data from the COronavirus in the LOwer Silesia (COLOS) registry. MATERIAL AND METHODS: The study group (834 patients of Caucasian patients) was retrospectively divided into three arms according to the risk achieved on the COVID-GRAM score calculated at the time of hospital admission (between February 2020 and July 2021): low, medium, and high risk. The Omnibus chi-square test, Fisher test, and Welch ANOVA were used in the statistical analysis. Post-hoc analysis for continuous variables was performed using Tukey's correction with the Games-Howell test. Additionally, the ROC analysis was performed over time using inverse probability of censorship (IPCW) estimation. The GRAM-COVID score was estimated from the time-dependent area under the curve (AUC). RESULTS: Most patients (65%) had a low risk of complications on the COVID-GRAM scale. There were 113 patients in the high-risk group (13%). In the medium- and high-risk groups, comorbidities occurred statistically significantly more often, e.g., hypertension, diabetes, atrial fibrillation and flutter, heart failure, valvular disease, chronic kidney disease, and obstructive pulmonary disease (COPD), compared to low-risk tier subjects. These individuals were also patients with a higher incidence of neurological and cardiac complications in the past. Low saturation of oxygen values on admission, changes in C-reactive protein, leukocytosis, hyperglycemia, and procalcitonin level were associated with an increased risk of death during hospitalization. The troponin level was an independent mortality factor. A change from low to medium category reduced the overall survival probability by more than 8 times and from low to high by 25 times. The factor with the strongest impact on survival was the absence of other diseases. The medium-risk patient group was more likely to require dialysis during hospitalization. The need for antibiotics was more significant in the high-risk group on the GRAM score. CONCLUSION: The COVID-GRAM score corresponds well with total mortality. The factor with the strongest impact on survival was the absence of other diseases. The worst prognosis was for patients who were unconscious during admission. Patients with higher COVID-GRAM score were significantly less likely to return to full health during follow-up. There is a continuing need to develop reliable, easy-to-adopt tools for stratifying the course of SARS-CoV-2 infection.

The Usefulness of the C2HEST Risk Score in Predicting Clinical Outcomes among Hospitalized Subjects with COVID-19 and Coronary Artery Disease.

BACKGROUND: Even though coronary artery disease (CAD) is considered an independent risk factor of an unfavorable outcome of SARS-CoV-2-infection, the clinical course of COVID-19 in subjects with CAD is heterogeneous, ranging from clinically asymptomatic to fatal cases. Since the individual C2HEST components are similar to the COVID-19 risk factors, we evaluated its predictive value in CAD subjects. MATERIALS AND METHODS: In total, 2183 patients hospitalized due to confirmed COVID-19 were enrolled onto this study consecutively. Based on past medical history, subjects were assigned to one of two of the study arms (CAD vs. non-CAD) and allocated to different risk strata, based on the C2HEST score. RESULTS: The CAD cohort included 228 subjects, while the non-CAD cohort consisted of 1956 patients. In-hospital, 3-month and 6-month mortality was highest in the high-risk C2HEST stratum in the CAD cohort, reaching 43.06%, 56.25% and 65.89%, respectively, whereas in the non-CAD cohort in the high-risk stratum, it reached: 26.92%, 50.77% and 64.55%. Significant differences in mortality between the C2HEST stratum in the CAD arm were observed in post hoc analysis only for medium- vs. high-risk strata. The C2HEST score in the CAD cohort could predict hypovolemic shock, pneumonia and acute heart failure during hospitalization, whereas in the non-CAD cohort, it could predict cardiovascular events (myocardial injury, acute heart failure, myocardial infract, carcinogenic shock), pneumonia, acute liver dysfunction and renal injury as well as bleedings. CONCLUSIONS: The C2HEST score is a simple, easy-to-apply tool which might be useful in risk stratification, preferably in non-CAD subjects admitted to hospital due to COVID-19.

Nutritional and Non-Nutritional Predictors of Low Spot Urinary Creatinine Concentration in Patients with Heart Failure.

Low spot urinary creatinine concentration (SUCR) is a marker of muscle wasting and clinical outcome. The risk factors for low SUCR in heart failure (HF) remain poorly understood. We explored the risk factors for low SUCR related to poor outcomes. In 721 HF patients (age: 52.3 ± 11 years, female: 14%, NYHA: 2.7 ± 0.7) SUCR and Dexa body composition scans were performed. BMI prior HF-onset, weight loss, and appendicular muscle mass were obtained. Each patient was classified as malnutrition or normal by GLIM criteria and three other biochemical indices (CONUT, PNI, and GRNI). Sarcopenia index (SI) as creatinine to cystatin C ratio was also calculated. Within 1 year, 80 (11.1%) patients died. In ROC curve we identified a SUCR value of 0.628 g/L as optimally discriminating surviving from dead. In low SUCR group more advanced HF, higher weight loss and catabolic components of weight trajectory (CCWT), more frequent under-nutrition by GLIM, and lower SI were observed. In multivariate analysis the independent predictors of low SUCR were SI, CCWT, and GNRI score. In conclusion: the risk of low SUCR was associated with a worse outcome. Low SUCR was associated with greater catabolism and sarcopenia but not with biochemical indices of malnutrition.

Differences in the Biomarker Profile of De Novo Acute Heart Failure versus Decompensation of Chronic Heart Failure.

The perception of acute heart failure (AHF) as a single entity is increasingly outdated, as distinct patient profiles can be discerned. Key heart failure (HF) studies have previously highlighted the difference in both the course and prognosis of de novo AHF and acute decompensated chronic HF (ADHF). Accordingly, distinct AHF profiles with differing underlying pathophysiologies of disease progression can be shown. We compared a range of selected biomarkers in order to better describe the profile of de novo AHF and ADHF, including the inter alia-serum lactate, bilirubin, matrix metallopeptidase 9 (MMP-9), follistatin, intercellular adhesion molecule 1 (ICAM-1), lipocalin and galectin-3. The study comprised 248 AHF patients (de novo = 104), who were followed up for one year. The biomarker data of the de novo AHF and ADHF profiles was then compared in order to link biomarkers to their prognosis. Our study demonstrated that, although there are similarities between each patient profile, key biomarker differences do exist-predominantly in terms of NTproBNP, serum lactate, bilirubin, ICAM-1, follistatin, ferritin and sTfR (soluble transferrin receptor). ADHF tended to have compromised organ function and higher risks of both one-year mortality and composite endpoint (one-year mortality or rehospitalization for heart failure) hazard ratios (HR) (95% CI): 3.4 (1.8-6.3) and 2.8 (1.6-4.6), respectively, both p < 0.0001. Among the biomarkers of interest: sTfR HR (95% CI): 1.4 (1.04-1.8), NGAL(log) (neutrophil gelatinase-associated lipocalin) HR (95% CI): 2.0 (1.3-3.1) and GDF-15(log) (growth/differentiation factor-15) HR (95% CI): 4.0 (1.2-13.0) significantly impacted the one-year survival, all p < 0.05.

Catabolic/Anabolic Imbalance Is Accompanied by Changes of Left Ventricular Steroid Nuclear Receptor Expression in Tachycardia-Induced Systolic Heart Failure in Male Pigs.

BACKGROUND: Steroid hormones play an important role in heart failure (HF) pathogenesis, and clinical data have revealed disordered steroidogenesis in male patients with HF. However, there is still a lack of studies on steroid hormones and their receptors during HF progression. Therefore, a porcine model of tachycardia-induced cardiomyopathy corresponding to HF was used to assess steroid hormone concentrations in serum and their nuclear receptor levels in heart tissue during the consecutive stages of HF. METHODS AND RESULTS: Male pigs underwent right ventricular pacing and developed a clinical picture of mild, moderate, or severe HF. Serum concentrations of dehydroepiandrosterone, testosterone, dihydrotestosterone, estradiol, aldosterone, and cortisol were assessed by enzyme-linked immunosorbent assay. Androgen receptor, estrogen receptor alpha, mineralocorticoid receptor, and glucocorticoid receptor messenger RNA levels in the left ventricle were determined by qPCR.The androgen level decreased in moderate and severe HF animals, while the corticosteroid level increased. The estradiol concentration remained stable. The quantitative real-time polymerase chain reaction revealed the downregulation of androgen receptor in consecutive stages of HF and increased expression of mineralocorticoid receptor messenger RNA under these conditions. CONCLUSIONS: In the HF pig model, deteriorated catabolic/anabolic balance, manifested by upregulation of aldosterone and cortisol and downregulation of androgen signaling on the ligand level, was augmented by changes in steroid hormone receptor expression in the heart tissue.

Urinary levels of novel kidney biomarkers and risk of true worsening renal function and mortality in patients with acute heart failure.

AIMS: Recent studies indicate the need to redefine worsening renal function (WRF) in acute heart failure (AHF), linking a rise in creatinine with clinical status to identify patients who develop 'true WRF'. We evaluated the usefulness of serial assessment of urinary levels of neutrophil gelatinase-associated lipocalin (uNGAL), kidney injury molecule-1 (uKIM-1), and cystatin C (uCysC) for prediction of 'true WRF'. METHODS AND RESULTS: In 132 patients with AHF, uNGAL, uKIM-1, and uCysC were measured using a highly sensitive immunoassay based on a single-molecule counting technology (Singulex, Alameda, CA, USA) at baseline, day 2, and day 3. Patients who developed WRF (a ≥0.3 mg/dL increase in serum creatinine or a >25% decrease in the estimated glomerular filtration rate from the baseline value) were differentiated into those 'true WRF' (presence of deterioration/no improvement in clinical status during hospitalization) vs. 'pseudo-WRF' (uneventful clinical course). 'True WRF' occurred in 13 (10%), 'pseudo-WRF' in 15 (11%), whereas the remaining 104 (79%) patients did not develop WRF. Patients with 'true WRF' were more often females, had higher levels of NT-proBNP, creatinine, and urea on admission, higher urine albumin to creatinine ratio at day 2, higher uNGAL at baseline, day 2, and day 3, and higher KIM-1 at day 2 (vs. pseudo-WRF vs. without WRF, all P < 0.05). Patients with pseudo-WRF did not differ from those without WRF. In the multivariable model, elevated uNGAL at all time points and uKIM-1 at day 2 remained independent predictors of 'true WRF'. CONCLUSION: Elevated levels of uNGAL and uKIM-1 may predict development of 'true WRF' in AHF.

Both iron excess and iron depletion impair viability of rat H9C2 cardiomyocytes and L6G8C5 myocytes.

BACKGROUND: Iron is presumed to play an important role in the functioning of cardiomyocytes and skeletal myocytes. There is scarcity of direct data characterising the cells functioning when exposed to iron depletion or iron overload in a cellular environment. There is some clinical evidence demonstrating that iron deficiency has serious negative prognostic consequences in heart failure (HF) patients and its correction brought clinical benefit. AIM: The viability of the cells upon unfavourable iron concentration in the cell culture medium and the presence of the molecular system of proteins involved in intracellular iron metabolism in these cells have been studied. METHODS: H9C2 rat adult cardiomyocytes and L6G8C5 rat adult skeletal myocytes were cultured for 24 h in optimal vs. reduced vs. increased iron concentrations. Intracellular iron content was measured by flame atomic absorption spectroscopy (FAAS). We analysed the mRNA expression of: ferritin heavy and light chains (FTH and FTL; iron storage proteins), myoglobin (MB, oxygen storage protein) ferroportin type 1 (FPN1; iron exporter), transferrin receptor type 1 (TfR1; iron importer), hepcidin (HAMP; iron metabolism regulator) using qPCR, the level of respective proteins using Western Blot (WB), and the viability of the cells using flow cytometry and cell viability tetrazolium reduction assay (MTS). RESULTS: Cardiomyocytes exposed to gradually reduced iron concentrations in the medium demonstrated a decrease in the mRNA expression of FTH, FTL, FPN1, MB, and HAMP (all R = -0.75, p < 0.05), indicating depleted iron status in the cells. As a consequence, the expression of TfR1 (R = 0.7, p < 0.05) was increased, reflecting a facilitated entrance of iron to the cells. The inverse changes occurred in H9C2 cells exposed to increased iron concentrations in the medium in comparison to control cells. The same pattern of changes in the mRNA expressions was observed in myocytes, and there was a strong correlation between analogous genes in both cell lines (all R > 0.9, p < 0.0001). WB analysis revealed the analogous pattern of changes in protein expression as an mRNA profile. Both iron depletion and iron excess impaired viability of cardiomyocytes and skeletal myocytes. CONCLUSIONS: Both rat cardiomyocytes and myocyte cells contain the set of genes involved in the intracellular iron metabolism, and both types of investigated cells respond to changing iron concentrations in the cultured environment. Both iron deficiency (ID) and iron overload is detrimental for the cells. This data may explain the beneficial effects of iron supplementation in patients with ID in HF.

Late Cardiac Tamponade as a Result of Parietal Pericardium Erosion.

Late onset cardiac tamponade is a rare and particularly challenging (both from diagnostic and management perspectives) complication of intracardiac lead implantation. We present a case of a late tamponade leading to cardiogenic shock, which occurred 1,164 days after implantable cardioverter-defibrillator (ICD) implantation. Open repair revealed unusual and, to our knowledge, not yet reported mechanism of the disease. A pressure sore caused by an ICD lead was found in the parietal layer of pericardium with no visible damage to the visceral layer. Conservative management in the described clinical scenario could be fatal, thus awareness of this pathomechanism of tamponade is critical.

[Intracardiac thrombi in pulmonary embolism of a priori non high risk: therapeutic dilemma]. / Skrzepliny wewnatrzsercowe w zatorowosci plucnej a priori niewysokiego ryzyka: dylematy terapeutyczne.

Pulmonary embolism (PE) of a priori non high risk according to ESC guidelines, but coexisting with intracardiac thrombi is potentially a life threatening disease. The recommendations regarding therapy in such situations are not clear. We report two cases of PE with coexisting intracardiac thrombi. The 74 year-old woman was admitted after previous cardiac arrest in the course of PE with the presence of intracardiac thrombi in right ventricle. Due to lack of clinical improvement during heparin administration she was treated with thrombolysis. The 72 year-old obese woman with hypertension, diabetes and previous stroke with right-sided paresis was admitted after 2 episodes of loss of consciousness, with intracardiac thrombus in both right and left heart. Due to contraindications to both surgery and thrombolysis, she was treated with heparin. Both women recovered successfully. These cases illustrate the importance of individual treatment strategy.

[Are age and educational level the determinants of hormonal parameters considered as indices of andropause?]. / Czy wiek i wyksztalcenie sa determinantami parametrów hormonalnych uznawanych za wskazniki andropauzy?

The involutionary processes in gonadal and adrenal glands are significant for male aging. The dynamics of hormonal changes in aging men seems to be individually differentiated and vary in distinct populations. Currently there are no data on social differences in hormonal parameters in men. The study was carried out in order to evaluate the age-related changes of hormonal parameters considered as indices of andropause and analyze the social gradients in these variables in healthy Polish men. Material comprised the data of 414 healthy men, inhabitants of Wroclaw, aged 32-79, examined in 2000 in DOLMED (Wroclaw, Lower Silesia). Serum levels of the following hormones were assessed using radioimmunological assays: free testosterone (FT), total testosterone (TT), estradiol (E2), dehydroepiandrosterone sulphate (DHEAS), luteinizing hormone (LH), sex hormone binding globulin (SHBG) and insulin-like growth factor 1 (IGF-1). The following indices were calculated: FAI (Free Androgen Index), TT/E2 and TT/LH. Among Polish men there were negative correlations between age and serum levels of FT, DHEAS, IGF-1, E2, and between age and FAI, TT/LH. The correlation between the DHEAS level and age was the strongest among all relationships here. The male aging was accompanied by the serum reduction, during 5 years: FT level of 4.8%, DHEAS--8.6% and IGF-1--5.0%. The reduction in serum DHEAS and IGF-1 levels reached 77.3% and 44.9% (respectively) between men aged 32-34 and the oldest subjects aged 75-79. The decrease in serum FT level between men aged 32-34 and those aged 70-74 was 38.2%. The relationships between age and E2 level and between age and TT/LH were not strong (respectively, beta = -0.10, p < 0.05 and beta = -0. 17, p < 0.001). The male aging was also accompanied by the increase in serum SHBG (11.7%/5 years) and LH levels (13.5%/5 years). Among male there were no age-related changes in the serum TT level and TT/E2. The results of a two-way ANOVA revealed that education significantly differentiated serum IGF-1 levels (independently on age). The highest IGF-1 levels were observed in men who had graduated from university, the lowest--in those who had finished the trade school at the very most. In contrast, there were no social differences in other analysed hormonal parameters.

[Hyperprolactinemia and sexual activity of men--clinical aspect]. / Hiperprolaktynemia a aktywnosc seksualna mezczyzn--aspekty kliniczne.

Hyperprolactinemia, particularly resulting from microprolactinoma, is known to induce erectile dysfunction. Contemporary published data do not allow to ascertain which prolactin (PRL) levels result in this type of sexual dysfunctions. The aim of this study was to evaluate the relationship between the extent of hyperprolactinemia and erectile dysfunction in 9 men with microprolactinoma and 8 patients with hyperprolactinemia as side-effects of sulpiride therapy. In all hyperprolactinemic males plasma PRL, LH, FSH and total testosterone levels were measured. The results showed that all patients with iatrogenic hyperprolactinemia were characterised by satisfactory sexual activity, although in 3 men hypotestosteronemia was revealed and in one patient gynecomastia was found. A range of PRL levels was 35-108 ng/ml. Among men with microprolactinoma the capability to lead a satisfactory sexual activity existed, even though in one patient PRL level was 2177 ng/ml, but in 3 other patients importance was observed when PRL concentrations were 281, 195 and 328 ng/ml. After bromocriptine therapy, when PRL levels diminished until 189, 78.3 and 110 ng/ml, the erectile dysfunction disappeared. Authors presume that sexual dysfunctions are not strictly connected with hyperprolactinemia and/or hypotestosterionemia, but probably are conditioned by other unexplicit factors (for example: a heterogeneous structure of PRL complexes).

[Overweight and obesity in urban population in Poland in years 1983-1999]. / Nadwaga i otylosc w populacji wielkomiejskiej w Polsce w latach 1983-1999.

There is a shortage of up-to-date data on the extent of the problem of overweight and obesity in Poland, although obesity is commonly considered as the 'epidemic of the end of the 20th century'. The aim of the study was to compare the percentages of overweight (BMI > or = 25) and obese (BMI > or = 30) adults from Wroclaw population in particular categories of age, sex and social status. Material comprised the data of 15,641 men and 19,121 women aged 21-60, occupationally active inhabitants of Wroclaw, examined in the DCDM 'DOLMED' in 1983-1999. BMI was used as a measure of general obesity (according to WHO categories). It was revealed that age, sex and social status significantly differentiated BMI of examined inhabitants of Wroclaw. In the subsequent decades of life mean BMI values increased, hence an increase of percentages of overweight and obese persons was observed. More than the half of men exceeded their proper relative mass before 40 years of age, whereas the 2/3 of them had BMI over 25 before the age of 50 (independently on their social background). The process of increasing percentages of overweight women was socially differentiated; between the 3rd and the 6th decade of life the percentages of overweight women increased among intelligence from 16 to 60%, among clerks from 18 to 72% and among workers from 27 to 83%. A sexual dimorphism resulted in fact that in men an age-related increase of overweight subjects (25 > or = BMI < 30) was observed, whereas in women an age-related increase of obese persons (BMI ? 30) was found. In an urban population in Poland in the 1990s the percentage of overweight persons (BMI l 25) exceeded 70% after the age of 50. Therefore--in the context of essential relationships between overweight and both mortality and morbidity--the health status of urban population in Poland is highly disturbing.