Longer Hospitalizations and Higher In-Hospital Mortality for Acute Heart Failure during the COVID-19 Pandemic in Larger vs. Smaller Cardiology Departments: Subanalysis of the COV-HF-SIRIO 6 Multicenter Study.

Background: The coronavirus disease-2019 (COVID-19) pandemic is surging across Poland, leading to many direct deaths and underestimated collateral damage. We aimed to compare the influence of the COVID-19 pandemic on hospital admissions and in-hospital mortality in larger vs. smaller cardiology departments (i.e., with ≥ 2000 vs. < 2000 hospitalizations per year in 2019). Methods: We performed a subanalysis of the COV-HF-SIRIO 6 multicenter retrospective study including all patients hospitalized in 24 cardiology departments in Poland between January 1, 2019 and December 31, 2020, focusing on patients with acute heart failure (AHF) and COVID-19. Results: Total number of hospitalizations was reduced by 29.2% in larger cardiology departments and by 27.3% in smaller cardiology departments in 2020 vs. 2019. While hospitalizations for AHF were reduced by 21.8% and 25.1%, respectively. The length of hospital stay due to AHF in 2020 was 9.6 days in larger cardiology departments and 6.6 days in smaller departments (p < 0.001). In-hospital mortality for AHF during the COVID-19 pandemic was significantly higher in larger vs. smaller cardiology departments (10.7% vs. 3.2%; p < 0.001). In-hospital mortality for concomitant AHF and COVID-19 was extremely high in larger and smaller cardiology departments accounting for 31.3% vs. 31.6%, respectively. Conclusions: During the COVID-19 pandemic longer hospitalizations and higher in-hospital mortality for AHF were observed in larger vs. smaller cardiology departments. Reduced hospital admissions and extremely high in-hospital mortality for concomitant AHF and COVID-19 were noted regardless of department size.

Effect of reperfusion on vascular smooth muscle reactivity in three contraction models.

BACKGROUND: Ischemia and reperfusion remain inseparable elements of numerous medical procedures such as by-pass surgery, organ transplantation or other cardiology and intervention radiology. The contraction of the smooth muscle of the vessel is considered to be one of the basic components leading to impaired perfusion, an increase in the oxygen deficit of the endothelium of the vessel, and subsequently also to tissues vascularized by the vessel. Main aim of this study was to evaluate the effect of ischemia and reperfusion on vascular smooth muscle cells stimulated pharmacologically with mastoparan-7 (direct G-protein activator) in comparison to stimulation of G-protein coupled receptor agonist - phenylephrine, and direct calcium channel activator - Bay K8644. MATERIAL AND METHODS: Experiments were performed on isolated and perfused tail artery of Wistar rats. Contraction force in our model was measured by increased level of perfusion pressure with a constant flow. RESULTS: Concentration-response curves obtained for phenylephrine, mastoparan-7 and Bay K8644 presented a sigmoidal relation. Ischemia induced hyporreactivity of vessels, whereas during reperfusion the significant time related hyperreactivity for phenylephrine and mastoparan-7 only but not for Bay K8644. These reactions were secondary to the modulation of calcium influx from intra- and extracellular calcium stores. CONCLUSIONS: Results of our experiments suggest that mastoparan-7 significantly induces contraction of vascular smooth muscle cells not only for controls but in the presence of ischemia and reperfusion too. Potential therapeutic applications of the observed reactions are important. They may include regenerative processes within the nervous system, studies on the improvement of blood flow within the microcirculation, or antimicrobial activity. Modulation of the G protein-phospholipase C response may also be an interesting point of action of future drugs modifying the response to stimulation during ischemia in particular, such activities could take place during the transport of organs for transplantation.

Inhibitors of sodium-glucose transport protein 2: A new multidirectional therapeutic option for heart failure patients.

Several mechanisms have been suggested to explain positive cardiovascular effects observed in studies with sodium-glucose co-transporter 2 (SGLT2) inhibitors. The reduction in glucose reabsorption in proximal tubuli induced by SGLT2 inhibitors increases urinary glucose and sodium excretion resulting in increased osmotic diuresis and consequently in decreased plasma volume, followed by reduced preload. In addition, the hemodynamic effects of SGLT2 inhibition were observed in both hyper and euglycemic patients. Due to the complex and multidirectional effects induced by SGLT2 inhibitors, this originally antidiabetic group of drugs has been successfully used to treat patients with heart failure as well as for subjects with chronic kidney disease. Moreover, their therapeutic potential seems to be even broader than the indications studied to date.

Comparison of reorganized versus unaltered cardiology departments during the COVID-19 era: A subanalysis of the COV-HF-SIRIO 6 study.

BACKGROUND: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, numerous cardiology departments were reorganized to provide care for COVID-19 patients. We aimed to compare the impact of the COVID-19 pandemic on hospital admissions and in-hospital mortality in reorganized vs. unaltered cardiology departments. METHODS: The present research is a subanalysis of a multicenter retrospective COV-HF-SIRIO 6 study that includes all patients (n = 101,433) hospitalized in 24 cardiology departments in Poland between January 1, 2019 and December 31, 2020, with a focus on patients with acute heart failure (AHF). RESULTS: Reduction of all-cause hospitalizations was 50.6% vs. 21.3% for reorganized vs. unaltered cardiology departments in 2020 vs. 2019, respectively (p < 0.0001). Considering AHF alone respective reductions by 46.5% and 15.2% were registered (p < 0.0001). A higher percentage of patients was brought in by ambulance to reorganized vs. unaltered cardiology departments (51.7% vs. 34.6%; p < 0.0001) alongside with a lower rate of self-referrals (45.7% vs. 58.4%; p < 0.0001). The rate of all-cause in-hospital mortality in AHF patients was higher in reorganized than unaltered cardiology departments (10.9% vs. 6.4%; p < 0.0001). After the exclusion of patients with concomitant COVID-19, the mortality rates did not differ significantly (6.9% vs. 6.4%; p = 0.55). CONCLUSIONS: A greater reduction in hospital admissions in 2020 vs. 2019, higher rates of patients brought by ambulance together with lower rates of self-referrals and higher all-cause in-hospital mortality for AHF due to COVID-19 related deaths were observed in cardiology departments reorganized to provide care for COVID-19 patients vs. unaltered ones.

High on-treatment platelet reactivity to aspirin in patients after myocardial infarction.

Aspirin (ASA) is widely used as an antiplatelet therapeutic drug in secondary prevention. Last years brought many reports on ASA resistance or high on-treatment platelet reactivity (HTPR) to aspirin.This study is a post-hoc prospective analysis with 30 patients evaluated during follow up on average of 6.3 years after hospitalization from myocardial infarction. The examined population was divided into two subgroups according to the response to ASA. In order to estimate the function of blood platelets and their responsiveness to acetylsalicylic acid therapy, ASPI-test was used. The measurements were performed by the method of whole blood impedance aggregometry. During long-term follow up significantly higher percentage of high platelet reactivity was observed, compared with previous visits (p = 0.00001). Considering clinical endpoints of the research that were connected with coronary disease, no differences were obtained.The frequency of HTPR to aspirin in this study was higher than data reported in literature among subjects with CV diseases. In long-term observation the highest percentage of ASA non-responders was reported (58.6%). HTPR to aspirin did not affect the presence of the clinical endpoints for the study.

Determinants of the Level of Anti-SARS-CoV-2 IgG ANTibodiEs after Vaccination (DANTE-SIRIO 7) Study in a Large Cohort of Healthcare Workers.

The aim of this study was to determine anti-SARS-CoV-2 IgG concentrations and their major determinants in healthcare workers (HCWs) after full vaccination with the BNT162b2 vaccine. We recruited 847 individuals vaccinated with two doses of the BNT162b2 vaccine, who completed the questionnaire, and whose antibody concentrations were tested after 3 and 6 months after full vaccination. Anti-SARS-CoV-2 IgG levels were measured on the routinely employed Siemens Atellica system. The cutoff for positivity was ≥21.8 BAU/mL. Three and 6 months after vaccination, the majority of participants were seropositive. Median concentrations of anti-SARS-CoV-2 IgG significantly decreased from 1145 BAU/mL (IQR: 543-2095) to 225 BAU/mL (IQR: 100-510). Major positive determinants of antibody levels were fever after both doses of vaccine, prior-COVID-19 exposure, and muscle pain after the first dose. Lack of symptoms after the second dose and time since vaccination were significant negative determinants of anti-SARS-CoV-2 IgG concentrations. No other factors, including age and gender, or underlying comorbidities had a significant effect on antibody levels in HCWs. The anti-SARS-CoV-2 response after two doses of BNT162b2 vaccine was independently associated with prior-COVID-19 exposure, time since vaccination, and the occurrence of symptoms after either dose of vaccine. Easily reportable adverse reactions may facilitate the identification of immune response in HCWs.

Impact of COVID-19 pandemic on acute heart failure admissions and mortality: a multicentre study (COV-HF-SIRIO 6 study).

AIMS: The coronavirus disease-2019 (COVID-19) pandemic has changed the landscape of medical care delivery worldwide. We aimed to assess the influence of COVID-19 pandemic on hospital admissions and in-hospital mortality rate in patients with acute heart failure (AHF) in a retrospective, multicentre study. METHODS AND RESULTS: From 1 January 2019 to 31 December 2020, a total of 101 433 patients were hospitalized in 24 Cardiology Departments in Poland. The number of patients admitted due to AHF decreased by 23.4% from 9853 in 2019 to 7546 in 2020 (P < 0.001). We noted a significant reduction of self-referrals in the times of COVID-19 pandemic accounting 27.8% (P < 0.001), with increased number of AHF patients brought by an ambulance by 15.9% (P < 0.001). The length of hospital stay was overall similar (7.7 ± 2.8 vs. 8.2 ± 3.7 days; P = not significant). The in-hospital all-cause mortality in AHF patients was 444 (5.2%) in 2019 vs. 406 (6.5%) in 2020 (P < 0.001). A total number of AHF patients with concomitant COVID-19 was 239 (3.2% of AHF patients hospitalized in 2020). The rate of in-hospital deaths in AHF patients with COVID-19 was extremely high accounting 31.4%, reaching up to 44.1% in the peak of the pandemic in November 2020. CONCLUSIONS: Our study indicates that the COVID-19 pandemic led to (i) reduced hospital admissions for AHF; (ii) decreased number of self-referred AHF patients and increased number of AHF patients brought by an ambulance; and (iii) increased in-hospital mortality for AHF with very high mortality rate for concomitant AHF and COVID-19.

Diurnal variation in platelet inhibition by clopidogrel.

Morning increase in the occurrence of myocardial infarction, stroke and sudden cardiac death is a well-recognized phenomenon, which is in line with a morning enhancement of platelet aggregation. We investigated whether platelet inhibition during clopidogrel and aspirin therapy varies during the day. Fifty-nine consecutive patients (45 men and 14 women) with first ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary interventions (pPCI) on dual antiplatelet therapy were prospectively enrolled into the study. Blood samples were collected 4 days after start of clopidogrel treatment at 6.00 a.m., 10.00 a.m., 2.00 p.m. and 7.00 p.m. Arachidonic acid and adenosine diphosphate (ADP)-induced platelet aggregation were assessed by impedance aggregometry. Platelet inhibition by clopidogrel was lowest in the midmorning: median ADP-induced platelet aggregation was 55%, 17% and 27% higher at 10.00 a.m. compared to 6.00 a.m., 2.00 p.m. and 7.00 p.m., respectively (p < 0.002). Nonresponsiveness to clopidogrel defined according to the device manufacturer was 2.4-fold more frequent in the midmorning than in the early morning. We observed a more pronounced midmorning increase in ADP-induced platelet aggregation in diabetic patients when compared to non-diabetics. In contrast, no diurnal variation in the antiplatelet effect of aspirin was observed. In conclusion, in patients presenting with STEMI undergoing pPCI, platelet inhibition by clopidogrel is less strong in the midmorning hours. This periodicity in platelet aggregation in patients on dual antiplatelet therapy should be taken into consideration when assessing platelet function in clinical studies.

Therapeutic Drug Monitoring of Carbamazepine: A 20-Year Observational Study.

BACKGROUND: Carbamazepine (CBZ) is a first-generation anticonvulsant drug. Hence, in certain cases, therapeutic drug monitoring (TDM) supports pharmacotherapy. METHODS: The presented research was based on a retrospective analysis including 710 ambulatory and hospitalized patients treated with CBZ between the years 1991 and 2011. The method used for the determination of the CBZ concentration was fluorescence polarization immunoassay (FPIA) performed using an Abbott GmbH TDx automatic analyzer, with the therapeutic range for carbamazepine being 4-12 µg/mL. RESULTS: The therapeutic range was observed more often in patients between 3 and 17 years of age compared with the population ≥18 years of age (73.5% vs. 68.8%). The therapeutic level was exceeded less frequently in the population between 3 and 17 years of age despite them being given a significantly higher dose per kilogram of body weight than in the population ≥18 years of age (13.64 mg/kg vs. 10.43 mg/kg, p < 0.0001). Patients ≥18 years of age were statistically significantly more likely to be in the group with a suspected drug overdose (73.9% vs. 26.1%), and suicide attempts only occurred in elderly patients (100.0% vs. 0.0%, p = 0.003). CONCLUSION: The results of the TDM of CBZ showed that only 71% of all samples were at the therapeutic level. To ensure the maximum efficacy and safety of the therapy, it is necessary to monitor the concentration of CBZ regardless of sex and age.

Medication adherence and its determinants in patients after myocardial infarction.

Non-adherence to prescribed medication is a serious limitation of long-term treatment in patients after myocardial infarction (MI), which can be associated with medical, social and economical consequences. Improvement of medication adherence has been shown to be a challenge for healthcare providers. The aim of this study was to evaluate changes in medication adherence and variability of adherence determinants during follow-up in patients after MI. A single-center, cohort observational study was conducted in 225 post-MI patients treated with primary coronary intervention (PCI) (27% women and 73% men) aged 30-91 years. Adherence was defined as availability of evaluated drugs within 1-year after discharge from hospital, based on completed prescriptions data obtained from the National Health Fund. The analysis of therapeutic plan realization (adherence to medication prescribed at discharge from hospital) embraced only reimbursed drugs: ACEIs (ramipril, perindopril), P2Y12 receptor inhibitors (clopidogrel) and statins (atorvastatin, simvastatin, rosuvastatin). Sufficient adherence was defined as ≥ 80%. During 1-year follow-up, adherence for all three drug classes was 64 ± 25%, with 67 ± 32% for ACEIs, 62 ± 34% for P2Y12 receptor inhibitor and 64 ± 32% for statins. A gradual decline in adherence was observed from 65% ± 26% in the first quarter of follow-up to 51% ± 34% in the last quarter of follow-up (p < 0.00001). Sufficient adherence for all drugs classes was found only in 29% of patients throughout the whole follow-up period (44% for ACEI, 36% for P2Y12 receptor inhibitor and 41% for statins). According to a multivariate analysis, age, prior CABG, level of education, place of residence, economic status and marital status were independent predictors of drug adherence. Whereas patients > 65 years and having a history of prior CABG more often had an insufficient adherence to drugs, married and hypertensive patients, city inhabitants and patients with higher education tended to have a sufficient drug adherence. Adherence to pharmacotherapy after myocardial infarction decreases over time in a similar manner for all pivotal groups of drugs prescribed after MI. A number of socioeconomic and clinical factors have been identified to affect medication adherence over time.

Evaluation of Vascular Endothelial Growth Factor A and Selected Parameters of Coagulation and Fibrinolysis in a Group of Patients with Subarachnoid Haemorrhage.

Introduction. Subarachnoid hemorrhage (SAH) is currently one of the most serious diseases of the central nervous system. To reduce the negative consequences of SAH and help clinicians to assess the patient's condition, there are attempts to search for new diagnostic markers, which quickly and accurately allow for the proper diagnosis. The aim of this research was the concentration and activity of Vascular Endothelial Growth Factor A (VEGF-A) and selected parameters of coagulation and fibrinolysis in the blood of patients with SAH. Serum levels of VEGF-A in patients diagnosed with SAH are measured to assess the correlation between VEGF-A and the clinical condition of patient. This may help with proper therapeutics and better prognosis. Methods. The study involved 85 patients with subarachnoid hemorrhage. The control group consisted of 45 healthy subjects, sex and age matched. The following parameters were determined: APTT (Activated Partial Thromboplastin Time), INR (International Normalized Ratio), D-dimers and fibrinogen concentration, and the concentration of VEGF-A by ELISA (R&D USA). Results. The average concentration of VEGF-A in the study group was significantly lower compared to the control group. The D-dimer concentration was higher in patients with SAH but the difference was not significant. Coagulation parameters such as INR, APTT, and fibrinogen did not show significant differences between investigated groups. Conclusions. VEGF-A cannot be an independent marker of SAH. Selected parameters of coagulation and fibrinolysis such as D-dimers, INR, APTT, and fibrinogen should not be used as markers of SAH.

Therapeutic drug monitoring of digoxin-20 years of experience.

BACKGROUND: Digoxin is the oldest drug used in the pharmacotherapy of heart failure (HF). However, digoxin remains an important therapeutic option for patients with persistent symptoms of HF occurring despite the implementation of standard pharmacotherapy. Digoxin concentration serum (SCD) should equal 1-2ng/ml. The aim of our study was to measure of SCD among the hospitalized patients as well as to determine the selected factors influencing the concentration of the digoxin in the blood. METHODS: The presented research was based on a retrospective analysis including 2149 patients treated with digoxin and hospitalized between 1980 and 2000. Was used for the determination of SCD automatic analyzer TDX ABBOTT GmbH - fluorescence polarization immunoassay (FPIA), with therapeutic range for digoxin of 0.8-2.0ng/ml. RESULTS: Average SCD result in the study population was located within the therapeutic range and amounted 1.06ng/ml (55.7% of patients). Statistically significant differences in digoxin level were observed depending on the way of medicine administration (p=0.000001) and the daily amount (p=0.001). Moreover, statistically significant differences in digoxin level were observed depending on sex (p=0.00002). CONCLUSIONS: An elevated level of digoxin was observed in the case of patients who received the medication both orally and intravenously, together with an increase in the daily amount of digoxin doses. It was confirmed that an elevated digoxin level occurs in the course of treatment in the case of women.

Acetylsalicylic acid resistance risk factors in patients with myocardial infarction.

BACKGROUND: Despite its commonly recognized benefits in the cardiovascular disease setting, an issue of resistance to this drug has lately emerged. The aim of this research was assessment of the phenomenon of acetylsalicylic acid (ASA) resistance and its risk factors in patients treated for myocardial infarction. METHODS: This study is a post-hoc analysis of a previous prospective study with approximately 200 patients treated for myocardial infarction with a coated formulation of ASA. The population was divided into two subgroups according to the response to ASA. ASA responsiveness was assessed using the arachidonic acid-dependent platelet aggregation (ASPI-test). The measurements were performed using the technique of impedance aggregometry. RESULTS: The prevalence of aspirin resistance among the study population was 6.2%. All analyzed aggregometric parameters (including ASPI-test, adenosine diphosphate dependent platelet aggregation - ADP-test, bleeding time measurement) showed significant differences between both subgroups. ASA resistant patients had higher concentrations of brain natriuretic peptide (BNP), high-sensitivity C-reactive protein (hs-CRP), leukocytes (WBC) and platelets (PLT) but lower concentrations of hemoglobin (HGB). The temporal point analysis for both subgroups showed aspirin resistance incidence peak in patients at 9 months after myocardial infarction. CONCLUSIONS: The prevalence of aspirin resistance in our study population is comparable with rates reported in literature among patients with cardiovascular diseases. There is a possible relation between aspirin resistance and clopidogrel resistance. Presence did not affect the incidence of the clinical end-points.

Prasugrel overcomes high on-clopidogrel platelet reactivity in the acute phase of acute coronary syndrome and maintains its antiplatelet potency at 30-day follow-up.

BACKGROUND: The aim of this study was to assess antiplatelet effect of prasugrel in acute coronary syndrome (ACS) patients with high on-treatment platelet reactivity (HTPR) on clopidogrel, undergoing percutaneous coronary intervention (PCI). METHODS: A prospective, platelet reactivity-guided, parallel-group, open-label study including 71 patients pretreated with clopidogrel 600 mg and assigned either to prasugrel (30 mg loading dose, 10 mg maintenance dose; n = 46) or clopidogrel (150 mg maintenance dose for 6 days and thereafter 75 mg maintenance dose; n = 25) regimen, based on vasodilator-stimulated phosphoprotein (VASP)-assessed platelet reactivity index (PRI; > 50% vs. ≤ 50%) measured next morning post-PCI. RESULTS: Median PRI value after switch to prasugrel sharply declined at 24 h (70.0 [61.3-75.6] vs. 11.9 [6.8-25.7]%; p < 0.000001) and slightly but significantly rose between 24 h and 30 days (27.9 [15.5-46.8]%; p < 0.0006). In contrast, median PRI values in the clopidogrel group were similar at baseline and at 24 h (25.1 [13.7-40.2] vs. 22.0 [18.4-36.8]%; p = NS) and then modestly rose at 30 days (30.3 [20.4-45.7]%; p < 0.03). The prevalence of HTPR decreased in the prasugrel group between baseline and 24 h measurements (100.0 vs. 4.3%; p < 0.0001). Rates of patients with HTPR at 24 h and 30 days were similar in both groups, so were the tendencies in patterns of platelet inhibition evaluated with multiple electrode aggregometry as compared with the VASP assay. CONCLUSIONS: Our study indicates that prasugrel overcomes HTPR on clopidogrel in the acute phase of interventionally treated ACS and maintains its antiplatelet potency in 30-day follow-up. Potential clinical benefits of personalized antiplatelet prasugrel-based therapy warrant further investigation in clinical ACS trials.