Humoral anti-SARS-CoV-2 response in patients with different long COVID phenotypes.

Long COVID (LC) is characterized by persistent symptoms following SARS-CoV-2 infection, with various mechanisms offered to explain its pathogenesis. This study explored whether adaptive humoral anti-SARS-CoV-2 responses differ in LC. Unvaccinated COVID-19 convalescents (n = 200) were enrolled, with 21.5% (n = 43) presenting LC three months post-infection. LC diagnosis was based on persistent symptom(s) and alterations in biochemical/clinical markers; three phenotypes were distinguished: cardiological, pulmonary, and psychiatric LC. All three phenotypes were characterized by significantly decreased seroprevalence of IgG antibodies against nucleocapsid (anti-NP). LC was associated with decreased odds of testing positive for anti-NP (OR = 0.35, 95%CI: 0.16-0.78, p = 0.001). Seropositive LC patients had lower anti-S1 and anti-S2 levels than individuals without LC, and those with pulmonary and psychological phenotypes also revealed decreased anti-RBD concentrations. The results indicate that LC can be characterized by diminished humoral response to SARS-CoV-2. The potential implication of this phenomenon in post-acute viral sequelae is discussed.

Characteristics and outcomes for patients with heart failure diagnosed according to the universal definition and classification of heart failure. Data from a single-center registry.

BACKGROUND: There are no data on the characteristics and outcomes for patients with heart failure (HF) with reduced (HFrEF), mildly reduced (HFmrEF), and preserved (HFpEF) ejection fraction diagnosed according to the universal definition and classification of HF. AIMS: We used the universal HF definition to compare baseline characteristics, hospital readmission and mortality rates in individuals with HFrEF, HFmrEF, and HFpEF diagnosed retrospectively. RESULTS: The study was designed as a single-center retrospective analysis of all consecutive 40732 hospital admissions between 2013 and 2021 in a tertiary department of cardiology. All patients with HF, defined according to the universal definition and classification of HF, were identified. The study included 8471 patients with a mean age of 65.1 (12.8) years, of whom 2823 (33.3%) were females. Most individuals had a prior diagnosis of HF (76.3%) and elevated N-terminal pro-B-type natriuretic peptide levels (99.0%) with a median of 1548 (629-3786) pg/ml. Mean ejection fraction (EF) was 36.2 (14.9)%. The median follow-up was 39.1 (18.1-70.5) months. The most frequent type of HF was HFrEF (n = 4947; 58.4%), followed by HFpEF (n = 1138; 28.2%) and HFmrEF (n = 2386; 13.4%). Urgent HF readmissions and all-cause deaths were highest in HFrEF (40.8% and 42.7%), followed by HFmrEF (25.4% and 31.5%) and HFpEF (15.2% and 23.8%, respectively). CONCLUSIONS: The highest rates of urgent HF readmissions and all-cause mortality were observed in patients with HFrEF, followed by HFmrEF and HFpEF. In all HF groups, the all-cause mortality rate was higher than the rates of urgent HF readmission.

Evaluation of the Levels of Selected Cytokines and Their Possible Influence on the Development of Cardiovascular and Pulmonary Complications in Patients after COVID-19.

Background and Objectives: The aim of this study was to evaluate the levels of selected cytokines and their possible influence on the development of cardiovascular and pulmonary complications in patients hospitalized at the Silesian Centre for Heart Disease in Zabrze after having undergone COVID-19. Materials and methods: The study included 76 randomly selected patients from the SILCOVID-19 database. The median time from symptom onset to the study visit was 102 (86-118) days. The median age of the study group was 53 (44-60) years. Assays of a panel of 30 cytokines were carried out in the serum of patients on a Luminex100 platform using the Milliplex MAP kit from Merck KGaA Germany. Results: There were no statistically significant differences in most of the cytokines analyzed between patients with confirmed or excluded lung lesions or cardiac abnormalities. Additionally, no statistically significant differences in cytokine concentrations according to gender, age, comorbidity of diabetes, renal disease, hypertension, increased risk of thrombotic disease, or psychological disorders were demonstrated. There were high concentrations of cytokines such as platelet-derived growth actor-AA (PDGF-AA), monocyte chemoattractant protein-1 (MCP-1), monokine-induced gamma interferon (MIG), and vascular endothelial growth factor-A (VEGF-A). Conclusions: No direct impact of the dependencies between a panel of cytokines and the incidence of cardiovascular and pulmonary complications in patients hospitalized at the Silesian Centre for Heart Disease in Zabrze after having undergone COVID-19 was demonstrated. The demonstration of high levels of certain cytokines (PDGF-AA, VEGF, MIG, and IP10) that are of significance in the development of many lung diseases, as well as cytokines (MCP-1) that influence the aetiopathogenesis of cardiovascular diseases seems to be highly concerning in COVID-19 survivors. This group of patients should receive further monitoring of these cytokine levels and diagnostic imaging in order to detect more severe abnormalities as early as possible and administer appropriate therapy.

Spot Urinary Creatinine Concentration in Patients with Chronic Heart Failure Identifies a Distinct Muscle-Wasting Phenotype with a Strikingly Different Risk of Mortality.

BACKGROUND: There is a raising awareness that heart failure (HF) is a highly heterogeneous, multiorgan syndrome with an increasing global prevalence and still poor prognosis. The comorbidities of HF are one of the key reasons for presence of various phenotypes with different clinical profile and outcome. Heterogeneity of skeletal muscles (SMs) quantity and function may have an impact on patient's phenotype. AIM: We intended to compare clinical characteristics of phenotypes defined by a combination of various SM mass taken as a fat-free compartment from DEXA scans and different levels of SUCR (Spot Urinary Creatinine). All-cause mortality with mortality predicted by MAGGIC in such phenotypes were compared. METHODS: In 720 HF patients with reduced ejection fraction (age: 52.3 ± 10 years, female: 14%, NYHA: 2.7 ± 0.7, LVEF: 24.3 ± 7.3%), admitted to the hospital for heart transplantation candidacy assessment, morning SUCR along with body composition scanning (DEXA) was performed. All study participants were dichotomized twice, first by low or normal appendicular muscle mass index (ASMI) and second by SUCR (Spot Urinary Creatinine) < and ≥of 1.34 g/L. Four study groups (phenotypes) were created as combinations of lower or higher SUCR and low or normal ASMI. RESULTS: Low ASMI was found in 242 (33.6%) patients, while the remaining 478 had normal muscle mass. In 446 patients (61.9%), SUCR was <1.34 g/L. During 3 years of follow-up, 223 (31.0%) patients died (all-cause). The phenotype of lower both ASMI and SUCR was associated with the highest mortality. The death rate in phenotype with both low ASMI and SUCR exceeded by 70% the risk estimated by MAGGIC. This difference was significant as judged by the 95% confidence interval for MAGGIC estimation. In Cox regression analysis adjusted for MAGGIC and parameters known to increase risk, the relative risk of patients with phenotype of low both ASMI and SUCR was elevated by 45-55% as compared to patients with all other phenotypes. The protective role of higher SUCR in patients with muscle wasting was, therefore, confirmed in Cox analysis. CONCLUSIONS: Measurement of SUCR in HF patients can identify clinical phenotypes with skeletal muscle wasting but strikingly different risk of death that is actually not captured by MAGGIC score. The higher level of SUCR was associated with similar risk independently of presence of muscle wasting. As the analysis of SUCR is cheap and easy to perform, it should be further tested as a potentially useful biomarker, which may precisely phenotype HF patients independently of their skeletal muscle status.

Intensive Statin Therapy Versus Upfront Combination Therapy of Statin and Ezetimibe in Patients With Acute Coronary Syndrome: A Propensity Score Matching Analysis Based on the PL-ACS Data.

Background We aimed to compare statin monotherapy and upfront combination therapy of statin and ezetimibe in patients with acute coronary syndromes (ACSs). Methods and Results The study included consecutive patients with ACS included in the PL-ACS (Polish Registry of Acute Coronary Syndromes), which is a national, multicenter, ongoing, prospective observational registry that is mandatory for patients with ACS hospitalized in Poland. Data were matched using the Mahalanobis distance within propensity score matching calipers. Multivariable stepwise logistic regression analysis, including all variables, was next used in propensity score matching analysis. Finally, 38 023 consecutive patients with ACS who were discharged alive were included in the analysis. After propensity score matching, 2 groups were analyzed: statin monotherapy (atorvastatin or rosuvastatin; n=768) and upfront combination therapy of statin and ezetimibe (n=768 patients). The difference in mortality between groups was significant during the follow-up and was present at 1 (5.9% versus 3.5%; P=0.041), 2 (7.8% versus 4.3%; P=0.019), and 3 (10.2% versus 5.5%; P=0.024) years of follow-up in favor of the upfront combination therapy, as well as for the overall period. For the treatment, rosuvastatin significantly improved prognosis compared with atorvastatin (odds ratio [OR], 0.790 [95% CI, 0.732-0.853]). Upfront combination therapy was associated with a significant reduction of all-cause mortality in comparison with statin monotherapy (OR, 0.526 [95% CI, 0.378-0.733]), with absolute risk reduction of 4.7% after 3 years (number needed to treat=21). Conclusions The upfront combination lipid-lowering therapy is superior to statin monotherapy for all-cause mortality in patients with ACS. These results suggest that in high-risk patients, such an approach, rather than a stepwise therapy approach, should be recommended.

Long-term prognostic scores may underestimate the risk of death in patients with heart failure with reduced ejection fraction in whom red cell distribution width is elevated.

INTRODUCTION: Risk prediction in patients with heart failure with reduced ejection fraction (HFrEF) is one of the key challenges for clinicians. Novel biomarkers aggregating several important pathophysiological pathways may modify the diagnostic discrimination of validated scores. The red cell distribution width (RDW) is a cheap and easily available measure of anisocytosis, and was shown to have a strong independent prognostic power in short- and medium­term prognosis in HFrEF. OBJECTIVES: Our aim was to assess the prognostic power of RDW in optimally treated chronic HFrEF, and to investigate whether different RDW may impact the prognostic accuracy of validated long­term scores in HFrEF. PATIENTS AND METHODS: The study included 551 patients at a median (interquartile range [IQR]) age of 54 (47-59) years, of whom 86.6% were men. The patients represented the median New York Heart Association class III (IQR, II-III), and ischemic etiology occurred in 56.6% of the cases. In all patients, RDW as a coefficient of variation was calculated, along with Meta­Analysis Global Group in Chronic Heart Failure Score (MAGGIC­HF) and Seattle Heart Failure Survival Model (SHFSM). RESULTS: The patients were followed for 5 years and all­cause mortality was assessed. We recorded 166 (30.1%) and 225 (40.8%) deaths at 3 and 5 years, respectively. Scores based on MAGGIC­HF and SHFSM algorithms for the respective prediction of 3- and 5­year mortality were calculated for each patient and compared with the observed mortality. There was a significant underestimation of mortality in the patients with RDW above 15.4% (reference values, 11.5%-14.5%), while in those with lower RDW SHFSM overestimated the actual risk. The excess mortality in the higher RDW group was confirmed by the Hosmer-Lemeshow statistic. CONCLUSIONS: The RDW has a strong prognostic value in chronic HFrEF, independently of the risk assessed by the MAGGIC­HF or the SHFSM score.

Prognostic Value of Spot Urinary Creatinine Concentration and Its Relationship with Body Composition Parameters in HF Patients.

BACKGROUND: Low 24-h urinary excretion of creatinine in patients with heart failure (HF) is believed to reflect muscle wasting and is associated with a poor prognosis. Recently, spot urinary creatinine concentration (SUCR) has been suggested as a useful prognostic factor in selected HF cohorts. This more practical and cheaper approach has never been tested in an unselected HF population. Moreover, neither the relation between SUCR and body composition markers nor the association of SUCR with the markers of volume overload, which are known to worsen clinical outcome, has been studied so far. The aim of the study was to check the prognostic value of SUCR in HF patients after adjusting for body composition and indirect markers of volume overload. METHODS: In 911 HF patients, morning SUCR was determined and body composition scanning using dual X-ray absorptiometry (DEXA) was performed. Univariable and multivariable predictors of log SUCR were analyzed. All participants were divided into quartiles of SUCR. RESULTS: In univariable analysis, SUCR weakly correlated with fat-free mass (R = 0.09, p = 0.01). Stronger correlations were shown between SUCR and loop diuretic dose (R = 0.16, p < 0.0001), NTproBNP (R = -0.15, p < 0.0001) and serum sodium (R = 0.16, p < 0.0001). During 3 years of follow-up, 353 (38.7%) patients died. Patients with lower SUCR were more frequently female, and their functional status was worse. The lowest mortality was observed in the top quartile of SUCR. In the unadjusted Cox regression analysis, the relative risk of death in all three lower quartiles of SUCR was higher by roughly 80% compared to the top SUCR quartile. Apart from lower SUCR, the significant predictors of death were age and malnutrition but not body composition. After adjustment for loop diuretic dose and percent of recommended dose of mineralocorticoid receptor antagonists, the difference in mortality vanished completely. CONCLUSIONS: Lower SUCR levels in HF patients are associated with a worse outcome, but this effect is not correlated with fat-free mass. Fluid overload-driven effects may link lower SUCR with higher mortality in HF.

The influence of severe mitral regurgitation on major adverse cardiac and cerebrovascular events after myocardial infarction in 1-year follow-up: Data from PL-ACS registry.

BACKGROUND: Mitral regurgitation (MR) is frequently observed in patients with myocardial infarction (MI). However, the incidence of severe MR in contemporary population is unknown. AIMS: The study evaluates the prevalence and prognostic impact of severe MR in contemporary population of patients with ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI). METHODS: The study group consists of 8062 patients enrolled in the Polish Registry of Acute Coronary Syndromes over the years 2017‒2019. Only the patients with full echocardiography performed during the index hospitalization were eligible. Primary composite outcome was 12-month major adverse cardiac and cerebrovascular events (MACCE) (death, non-fatal MI, stroke and heart failure [HF] hospitalization) compared between patients with and without severe MR. RESULTS: 5561 NSTEMI patients and 2501 STEMI patients were enrolled into the study. Severe MR occurred in 66 (1.19%) NSTEMI patients and 30 (1.19%) STEMI patients. Multivariable regression models revealed that severe MR is an independent risk factor of all-cause death in 12-month observation (odds ratio [OR], 1.839; 95% confidence interval [CI], 1.012‒3.343; P = 0.046) in all MI patients. Patients with NSTEMI and severe MR had higher mortality (22.7% vs. 7.1%), HF rehospitalization rate (39.4% vs. 12.9%) and MACCE occurrence (54.5% vs. 29.3%). Severe MR was associated with higher mortality (20% vs. 6%) and higher HF rehospitalization (30% vs. 9.8%), stroke (10% vs. 0.8%) and MACCE rates (50% vs. 23.1%) in STEMI patients. CONCLUSIONS: Severe MR is associated with higher mortality and MACCE occurrence in patients with MI in 12-month follow-up. Severe MR is an independent risk factor of all-cause death.

Infarct-related artery and long-term mortality following recurrent ST-segment elevation myocardial infarction. Insights from a Polish nationwide registry.

BACKGROUND: Recurrent ST-segment elevation myocardial infarction (rSTEMI) can be attributed to the same (target-vessel, TV-rSTEMI) or different culprit vessel (non-target, nonTV-rSTEMI) compared with the first infarction. We hypothesized that long-term mortality after rSTEMI depends on the infarct-related artery (the same or different compared with the first STEMI). METHODS: Using the Polish Registry of Acute Coronary Syndromes (PL-ACS) we retrospectively identified survivors of first STEMI treated with PCI who experienced rSTEMI. We divided rSTEMI into TV-rSTEMI and nonTV-rSTEMI. We compared clinical, angiographic, and procedural characteristics and utilized propensity score matching to adjust for baseline differences. Primary outcome was 1-, 3- and 5-year all-cause mortality. RESULTS: Between 2003 and 2019 a total of 3,411 patients (mean age 63.7 years, 76% male) had rSTEMI, of whom 1,916 (56%) had TV-rSTEMI and 1,495 (44%) had nonTV-rSTEMI. Median time since first infarction was 716 days (100, 1,807). Patients with nonTV-rSTEMI had higher body mass index (27.2 vs 26.7 kg/m2, P = .041), more arterial hypertension (77.4 vs 73.7%, P = .015) and atrial fibrillation (4.8 vs 3.3%, P = .02), and lower left ventricular ejection fraction (43 [35, 50] vs 45 [38, 50]%, P <.001) compared with TV-rSTEMI. On coronary angiography nonTV-rSTEMI more frequently presented with Thrombolysis In Myocardial Infarction >1 flow (25.8 vs 15.7%, P < .001), multivessel disease (51.9 vs 40.8%, P =.002), culprit lesion located in circumflex artery (22.6 vs 5.6%, P < .001), and more frequently underwent stenting (88.8 vs 76.1%, P < .001) compared with TV-rSTEMI. There was no difference in unadjusted 1-, 3- and 5-year mortality between nonTV-rSTEMI and TV-rSTEMI. After propensity score analysis, 807 well-matched pairs of patients were selected. Adjusted 1-, 3- and 5-year mortality remained similar between nonTV-rSTEMI and TV-rSTEMI (14.7 vs 14.4%, P = .88; 23.6 vs 23.1%, P = .81; 30.0 vs 32.0%, P = .50 respectively). CONCLUSIONS: Our study shows overall low frequency of rSTEMI. Patients with nonTV-rSTEMI have different clinical and angiographic characteristics compared with TV-rSTEMI. No long-term mortality difference was observed between both groups.

Prevalence of Insomnia in the Early Post-COVID-19 Recovery Period.

BACKGROUND: Sleep is a complex, reversible process that is responsible for the modulation of various physiological mechanisms. COVID-19-related sleep disorders are affecting different populations with a heterogenous prevalence, yet high rates among infected patients are frequently reported. The aim of the study is to assess the prevalence of insomnia in the early post-COVID-19 recovery period and explore the differences in the results acquired by the Athens Insomnia Scale (AIS) by gender and selected infection severity parameters. METHODS: The data presented in the paper come from a prospective, observational study on COVID-19 complications (SILCOV-19) consisting of 200 COVID-19 patients. The AIS was used for the quantitative measurement of insomnia symptoms based on ICD-10 criteria. RESULTS: 32% (n = 64) of all patients in the study group obtained results indicating sleep disturbances (>5 points on the scale), while 21.5% (n = 43) obtained results indicating insomnia (>10 points on the scale). The analysis of the results obtained by all patients in the AIS showed a significant correlation with the duration of symptoms (Spearman's rank-order: R = 0.18; p < 0.05), but not with the number of days spent in the hospital or age. Women achieved a higher score in overall AIS, as well as in questions assessing total sleep time, well-being the next day, physical and mental fitness the next day, and sleepiness during the day (p < 0.05). CONCLUSIONS: the prevalence of insomnia in the early post-COVID-19 recovery period is high.

Death without Previous Hospital Readmission in Patients with Heart Failure with Reduced Ejection Fraction-A New Endpoint from Old Clinical Trials.

BACKGROUND: Most of the drugs approved and registered for use in heart failure (HF) therapy were examined in randomized clinical trials (RCTs) with the primary composite endpoint of death or hospital readmission. This study aimed to analyze the rates of the newly calculated event: death without prior hospital readmission, in HFrEF patients in large RCTs to show that the newly defined endpoint probably delivers additional data on the structure of the composite endpoint and helps to interpret the results of interventional studies. METHODS: This study included RCTs on therapeutic interventions in HF patients. A literature search was performed, and 31 trials in which death without hospital admission could be calculated were included in the analyses. The death without a prior hospital admission endpoint was calculated as the difference between the composite endpoint rate (death or hospital readmission) and the readmission rate. The differences in the new endpoint between the study groups were calculated. RESULT: The death rates without prior hospital admission were lower in the intervention groups in five trials. In the SENIORS study, significant differences were found in the primary (composite) and death without previous hospital admission endpoints. In the ACCLAIM, VEST, and GISSI-HF STATIN trials, death without previous hospital admission was the only endpoint with a significant difference between the study groups. Moreover, the new endpoint rates were higher in the intervention group in the latter two studies. CONCLUSIONS: The new endpoint describing patients who died without prior hospital admission might be useful in previous and future interventional studies to provide additional data on the structure of the composite endpoint. Some therapies might reduce death without previous hospital admission rates, which could be beneficial, even without a reduction in overall long-term mortality.

Post-COVID­19 complications in hospitalized and nonhospitalized patients: the Silesian database of COVID­19 complications (SILCOV­19).

INTRODUCTION: Due to the extent of the pandemic, high prevalence and severity of complications in the early post­recovery period are expected. OBJECTIVES: This study aimed to compare the scope of early post-COVID­19 complications in patients who had the disease and were or were not hospitalized. PATIENTS AND METHODS: This was a prospective, observational, registry­based cohort study conducted at a tertiary cardiovascular hospital in Silesia, Poland. Interdisciplinary diagnostics, including cardiovascular, pneumatological, respiratory, neurological, and psychiatric tests, was performed during the study visit. All patients completed the study. Two­hundred unselected, adult, white men and women with the symptoms of acute COVID­19 were included, of which 86 patients had the disease but did not require hospitalization. RESULTS: The median (interquartile range) time from symptom onset to the study visit was 107 (87-117) and 105 (79-127) days in nonhospitalized and hospitalized patients, respectively. Lung lesions on high­resolution computed tomography were found in 10 (8.8%) and 33 (39.3%) of nonhospitalized and hospitalized patients, respectively (P <0.01); no lesions were visualized on chest X­ray images. Elevated platelet distribution width was found in more than 70% of the patients in both groups. More than half of the patients had insomnia, regardless of the hospitalization status. CONCLUSIONS: The abnormal platelet parameters, functional and radiological findings in the lungs, and insomnia were the most frequent short­term COVID­19 complications in hospitalized and nonhospitalized patients. Considering the number of patients who have had COVID­19 worldwide, a high burden of the post-COVID­19 complications might be expected.

Managed Care after Acute Myocardial Infarction (MC-AMI) improves prognosis in AMI survivors with pre-existing heart failure: A propensity score matching analysis of Polish nationwide program of comprehensive post-MI care.

BACKGROUND: Despite improvement in acute myocardial infarction (AMI) treatment, post-discharge mortality remains high. The outcomes are supposed to be even worse in patients with post-MI heart failure (HF), as only a half of patients with newly diagnosed HF survive four years. AIMS: The study aimed to analyze whether managed care after acute myocardial infarction (MC-AMI) is associated with better survival in AMI survivors with a pre-existing diagnosis of HF. RESULTS: The study included 7228 patients with a pre-existing diagnosis of HF who survived the hospitalization for AMI in Poland between November 2017 and December 2020, of whom 2268 (31.4%) were referred for the MC-AMI program. The median follow-up was 1.5 (0.7-2.3) years. In the unmatched analysis, patients without MC-AMI had more than twice higher 12-month mortality (21.8% vs. 9.9%; P <0.01) than MC-AMI participants. The difference remained significant after propensity score matching (16,8% vs. 10.0%; P <0.01). In multivariable analysis, participation in MC-AMI was an independent factor of 12-month survival. MC-AMI participants had a lower stroke rate (1.5% vs. 3.0%; P <0.01) and fewer hospital admissions due to HF (22.9% vs. 27.6%; P <0.01). CONCLUSIONS: After propensity score matching, participation in MC-AMI was associated with lower rates of stroke, HF hospitalizations, and all-cause mortality in the 12-month follow-up and was an independent factor of 12-month survival in AMI survivors with pre-existing HF.