Corrigendum: Secretoneurin levels are higher in dilated cardiomyopathy than in ischaemic cardiomyopathy: preliminary results.

[This corrects the article DOI: 10.3389/fcvm.2023.1297900.].

A Simple Risk Formula for the Prediction of COVID-19 Hospital Mortality.

SARS-CoV-2 respiratory infection is associated with significant morbidity and mortality in hospitalized patients. We aimed to assess the risk factors for hospital mortality in non-vaccinated patients during the 2021 spring wave in the Czech Republic. A total of 991 patients hospitalized between January 2021 and March 2021 with a PCR-confirmed SARS-CoV-2 acute respiratory infection in two university hospitals and five rural hospitals were included in this analysis. After excluding patients with unknown outcomes, 790 patients entered the final analyses. Out of 790 patients included in the analysis, 282/790 (35.7%) patients died in the hospital; 162/790 (20.5) were male and 120/790 (15.2%) were female. There were 141/790 (18%) patients with mild, 461/790 (58.3%) with moderate, and 187/790 (23.7%) with severe courses of the disease based mainly on the oxygenation status. The best-performing multivariate regression model contains only two predictors-age and the patient's state; both predictors were rendered significant (p < 0.0001). Both age and disease state are very significant predictors of hospital mortality. An increase in age by 10 years raises the risk of hospital mortality by a factor of 2.5, and a unit increase in the oxygenation status raises the risk of hospital mortality by a factor of 20.

Mortality of hospitalized patients with COVID-19: Effects of treatment options (vitamin D, anticoagulation, isoprinosine, ivermectin) assessed by propensity score matching, retrospective analysis.

INTRODUCTION: SARS-CoV-2 respiratory infection is associated with significant morbidity and mortality, especially in hospitalized high-risk patients. We aimed to evaluate the effects of treatment options (vitamin D, anticoagulation, isoprinosine, ivermectin) on hospital mortality in non-vaccinated patients during the 2021 spring wave in the Czech Republic. METHODS: Initially, 991 patients hospitalized in the period January 1, 2021, to March 31, 2021, with PCR-confirmed SARS-CoV-2 acute respiratory infection in two university and five rural hospitals were included in the study. After exclusion of patients with an unknown outcome, a total of 790 patients entered the final analysis. The effects of different treatments were assessed in this cohort by means of propensity score matching. RESULTS: Of the 790 patients, 282 patients died in the hospital; 37.7% were male and 33.3% were female. Age, sex, state of the disease, pneumonia, therapy, and several comorbidities were matched to simulate a case-control study. For anticoagulation treatment, 233 cases (full-dose) vs. 233 controls (prophylactic dose) were matched. The difference in mortality was significant in 16 of the 50 runs. For the treatment with isoprinosine, ivermectin, and vitamin D, none of the 50 runs led to a significant difference in hospital mortality. CONCLUSION: Prophylactic-dose anticoagulation treatment in our study was found to be beneficial in comparison with the full dose. Supplementation with vitamin D did not show any meaningful benefit in terms of lowering the hospital mortality. Neither ivermectin nor, isoprinosine was found to significantly decrease hospital mortality.

Point-of-care ultrasound (POCUS) in acute hospitalized older patients focused on hydration.

BACKGROUND: Acutely ill older patients frequently suffer not only from their acute disease, but also polymorbidity and frailty. Dehydration is another typical symptom, usually occurring in its both forms: low-intake dehydration and volume depletion. POCUS is goal-directed bedside ultrasound examination and several studies refer to its positive impact on hydration assessment. The aim of our study was to determine whether POCUS might influence (de)hydration diagnostics and/or treatments in older patients with acute illness. METHODS: We randomized 120 acutely ill patients, aged ≥65 years, into POCUS and non-POCUS groups. All participants underwent routine laboratory tests, including haematocrit, serum and urine osmolality, blood urea nitrogen (BUN), creatinine, BUN/creatinine ratio, and C-reactive protein (CRP). POCUS was performed twice during the first two days to determine chest and abdominal status, with inferior vena cava (IVC) measurements. Length of hospital stay (HL) and consumption of infused fluids (CIF) was evaluated too. Data were analysed with exploratory methods and appropriate statistics. RESULTS: Among all participants, the serum osmolality significantly correlated with age, BUN, creatinine and CIF. HL correlated with CRP and CIF. No significant correlations between IVC and other followed parameters were found. The POCUS group consumed significantly less infused fluids than the non-POCUS group, what could be influenced by POCUS examination of defined body compartments. CONCLUSION: Dehydration is a common feature in older individuals and its diagnostics is rather complicated. The role of POCUS in assessing hydration status remains unclear. However, our study showed, that ultrasound assessment provides next important information for comprehensive understanding of clinical status in older patients and can be beneficial for optimizing the treatment strategy, including fluid management decisions.

Slittable sheath supported right ventricular pacing lead implantation in persistent left superior vena cava with absent right superior vena cava: a case report.

BACKGROUND: Persistent left superior vena cava (PLSVC) is the most common variant of systemic venous drainage. In the absence of the right superior vena cava (RSVC), implantation of a right ventricular pacing lead may be challenging. Therefore specific implantation techniques and experiences in PLSVC are worth reporting. CASE PRESENTATION: We present a case report of a 90-year-old Caucasian female patient with PLSVC during single chamber pacemaker implantation due to the third-degree atrioventricular block. With common implantation techniques, we did not even reach the right ventricle. Therefore slittable CPS Direct ™ Universal sheath was employed to overcome the acute angle from PLSVC to tricuspid valve and ensure more fixation stability for longer 100-cm right ventricular lead placement. CONCLUSION: This case demonstrates safe implantation of 100-cm long right ventricular bipolar active fixation pacing lead using common slittable CPS Direct ™ Universal sheath after failed attempts with "C" and "J" stylet shaped electrode. This sheath provides different angle towards tricuspid valve and more fixation stability in patient with PLSVC and absent connection to right atrium.

A practical approach to assessment of non-adherence to antihypertensive treatment.

Non-adherence to antihypertensive treatment is frequent, complicates the care of hypertensive patients, represents one of the major causes of treatment failure and is linked with the increased risk of cardiovascular events. Identifying a non-adherent patient is one of the recent daily-practice tasks for which the ideal solution has not yet been found. Presence of certain clinical red flags should prompt the clinician to consider non-adherence. Chemical adherence testing using serum or urine antihypertensive levels is regarded as the best method so far and should be used if available. Alternatively, the check for prescription refills in the patient electronic medical records, or directly observed therapy with subsequent ambulatory blood pressure monitoring may be used. We suggest a simple algorithm to guide the clinicians to detect non-adherence in the practice.

Optically modified second harmonic generation in silicon oxynitride thin films via local layer heating.

Strong second harmonic generation (SHG) in silicon nitride has been extensively studied-among others, in terms of laser-induced SHG enhancement in Si3N4 waveguides. This enhancement has been ascribed to the all-optical poling induced by the coherent photogalvanic effect. Yet, an analogous process for Si3N4 thin films has not been reported. Our article reports on the observation of laser-induced threefold SHG enhancement in Si3N4 thin films. The observed enhancement has many features similar to all-optical poling, such as highly nonlinear power dependence, cumulative effect, or connection to the Si3N4-Si interface. However, identical experiments for low-oxygen silicon oxynitride thin films lead to complex behavior, including laser-induced SHG reduction. Following a thorough experimental study, including the effects of repetition rate or pulse length, the observed results were ascribed to heat-induced SHG variation. In addition to revealing a new mechanism of laser-induced SHG variation, our results also provide a means to identify this mechanism.

What is new in 2022 ESC guidelines on cardiovascular assessment and management of patients undergoing non­cardiac surgery.

In 2022, the European Society of Cardiology has published updated guidelines for the cardiovascular evaluation and management of patients undergoing non-cardiac surgery. In this article we briefly summarize the most important recommendations with an emphasis on their use in everyday clinical practice - from the complex assessment of cardiovascular risk and prediction of cardiovascular complications, through the indication of basic paraclinical examinations, the importance of biomarkers, adjustments to pharmacotherapy of heart failure, adjustments to anticoagulant and antiplatelet therapy, to other specifics of individual cardiovascular and other diseases and their importance in the perioperative period. Knowledge and use of these recommendations have the potential to improve the prognosis of patients undergoing various types of surgical procedures.

News in cardiology.

The article summarizes new advances in cardiology published in 2022, which have an impact to everyday practice of not only internists and cardiologists. The administration of polypill to patients after myocardial infarction (SECURE study), early pharmacotherapy of hypertension in pregnant women with blood pressure exceeding 140/90 mmHg (CHAP study), or the administration of dapagliflozin to patients with heart failure with preserved or mildly reduced ejection fraction (DELIVER study) have been shown to be effective. Patients with heart failure do not have to limit their sodium intake (SODIUM-HF study), on the contrary, they benefit from up-titration of guideline-recommended drugs to the maximum tolerated doses as quickly as possible (STRONG-HF study). For antihypertensives, it does not matter whether they are taken in the morning or in the evening (TIME study), nor has there been found any difference in the incidence of cardiovascular events with hydrochlorothiazide and chlortalidone (DCP study). In patients with increased cardiovascular risk, highly sensitive troponin should be measured before non-cardiac surgery as well as 24 and 48 hours after surgery to detect perioperative myocardial infarction. Different blood pressure and oxygenation targets in patients after resuscitation for out-of-hospital cardiac arrest do not affect the outcomes of their treatment.

Secretoneurin levels are higher in dilated cardiomyopathy than in ischaemic cardiomyopathy: preliminary results.

Background: Secretoneurin (SN) is a neuropeptide with potential utility as a biomarker of cardiovascular episodes. The main effect of SN is mediated through its inhibition of calmodulin-dependent kinase II (CaMKII), which influences calcium handling. We aimed to associate the levels of SN in plasma with different causes of heart failure. Methods: We prospectively enrolled consecutive patients with ischaemic (ICM) and dilated (DCM) cardiomyopathy from the outpatient heart failure clinic and healthy individuals. SN was analysed from venous blood by use of the ELISA method. SN plasma levels were compared in DCM, ICM and healthy individuals with non-parametric tests. Results: A total of 53 patients (81.1% male, 18.9% female; mean age 67.9 ± 12.6 years) and 34 healthy individuals (38% male, 62% female) were included in the analysis. Plasma SN levels were significantly higher in the dilated cardiomyopathy (38.8 ± 27 pmol/L) as compared with the ischaemic cardiomyopathy (19.7 ± 22.6 pmol/L) group (P = 0.006). There was no significant difference between females vs. males (27.1 ± 23 vs. 25.5 ± 26.2 pmol/L, P = NS). Plasma SN levels allowed DCM and ICM to be differentiated with 88% sensitivity and 61% specificity (P = 0.007), the cut of value is 13.3 pmol/L. Plasma SN levels differed significantly between healthy volunteers and both ICM (P < 0.0001) and DCM (P = 0.049). Plasma SN levels did not differ according to age and were not associated with comorbidities, left ventricular ejection fraction, heart failure medication, troponin, creatinine, or natriuretic peptide plasma levels. Conclusion: Plasma secretoneurin levels differed significantly in DCM vs. ICM, being higher in the former. Based on plasma SN levels, discrimination between DCM and ICM might be possible. Healthy individuals produce higher SN plasma levels than stable HFrEF patients.

Secretoneurin as a Novel Biomarker of Cardiovascular Episodes: Are We There Yet? A Narrative Review.

Secretoneurin (SN) is a 33 amino-acid evolutionary conserved neuropeptide from the chromogranin peptide family. SN's main effects may be cardioprotective and are believed to be mediated through its inhibition of calmodulin-dependent kinase II (CaMKII), which influences intracellular calcium handling. SN inhibition of CaMKII suppresses calcium leakage from the sarcoplasmic reticulum through the ryanodine receptor. This action may reduce the risk of ventricular arrhythmias and calcium-dependent remodelling in heart failure. SN is also involved in reducing the intracellular reactive oxygen species concentration, modulating the immune response, and regulating the cell cycle, including apoptosis. SN can predict mortality in different disease states, beyond the classical risk factors and markers of myocardial injury. Plasma SN levels are elevated soon after an arrhythmogenic episode. In summary, SN is a novel biomarker with potential in cardiovascular medicine, and probably beyond.

Acute infections in kidney transplant recipients.

Immunosuppressed kidney transplant recipients have a high risk of infectious complications. A variety of infections of viral, bacterial, or mycotic etiology, including opportunistic infections, occur in this group of patients, but bacterial infections are primarily responsible for the high infection-related mortality. Of the bacterial infections, urinary tract infections and pneumonia are the most common, often requiring hospitalization and temporary reduction of immunosuppressive therapy after consultation of the transplant center. In addition to symptoms due to the location of the infection, fever is often present. The differential diagnosis of fever and/or high inflammatory activity is specific to patients after kidney transplantation. In addition to infectious causes, we consider drug-related fever, a rejection episode, a relapse of systemic disease or in patients with graft failure in dialysis treatment graft intolerance syndrome (“symptomatic graft”). Saving the patients life, which often requires a significant reduction in immunosuppressive therapy, always takes precedence over preventing a rejection episode. Infection prevention is an integral part of the care of transplant patients, including the recommendation of vaccination where possible.

Use of telemedicine in patients with heart failure.

Chronic heart failure (HF), like any chronic disease, is a medical and socioeconomic burden. The number of patients with HF is increasing and our effort is to apply the most effective way of care in practice, preferably together with using telemedicine. Early diagnosis, therapy establishment and reduction of rehospitalizations play the key role in HF management. For patients for whom we add telemedicine (telephone consultation, physiological data transfer, data transfer from implantable devices, teleconsultation) and especially if we are able to provide the background of a well-functioning telemedicine center that is able to respond promptly to the data, we can recognize and respond to the deterioration in health status in a timely manner. Telemedicine has benefit in all aspects of care mentioned above, but mostly in the reduction of re-hospitalizations, which is related to the reduction of morbidity and mortality. Telemedicine in HF is also cost-effective.

Whats new in 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice?

2021 ESC Guidelines on cardiovascular disease prevention in clinical practice provides a comprehensive view on preventive cardiology. It presents strategies to reduce the burden of atherosclerotic cardiovascular disease (CVD), both at the individual level and at the population level. Healthy lifestyle and aggressive control of cardiovascular risk factors remain the cornerstone of prevention. Classification of individuals into risk groups based on their clinical characteristics followed by a stepwise treatment-intensification is a novel recommended approach. Updated risk charts - SCORE2 and SCORE2-OP - are intended for estimation of 10-year fatal and non-fatal CVD risk in apparently healthy individuals. Targets and goals for LDL cholesterol, blood pressure, and glycaemic control remain as recommended in recent ESC Guidelines.

Whats new in 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST segment elevation?

The article sumarizes the 2020 ESC Guidelines for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation. The diagnostics of ACS consists in assessment of chest pain, EKG and cardiac troponin. Troponin should be evaluated by high sensitivity assay. 0h/1h algorithms should be used to rule-in or rule-out ACS. Patients with a positive troponin have higher risk of cardivascular events and mortality and the early invasive treatment should be applied in these patients. In the guidelines several antithrombotic stretegies for different clinical conditions are mentioned, where the cornerstone for the length and intensity of antithrombotic treatment is the evaluation of bleeding risk. Further on the revascularization aspects and strategies are debated in the guidelines. Finally there are mentioned two specific conditions of ACS - Myocardioal infarction with non-obstructive coronary arteries and Spontaneous coronary artery dissection.

Comprehensive approach to a patient with arterial hypertension and dyslipidemia.

Arterial hypertension together with dyslipidemia, diabetes and smoking are the most severe risk factors for cardiovascular (CV) disease. The Czech Republic is among the countries with a high risk of cardiovascular disease. To reduce cardiovascular mortality and morbidity in our patients, a comprehensive approach to treatment and, in most cases, aggressive control of all risk factors is needed. This article summarizes current diagnostic and therapeutic procedures for arterial hypertension and dyslipidaemia, as well as the concept of vascular age, which can help us to communicate CV risk with patients.

The Agreement of a Two- and a Three-Dimensional Speckle-Tracking Global Longitudinal Strain.

Background: Two-dimensional (2D) and three-dimensional (3D) speckle-tracking echocardiography (STE) enables assessment of myocardial function. Here, we examined the agreement between 2D and 3D STE measurement of a global longitudinal strain (GLS) in patients with normal left ventricle, reduced ejection fraction, and cardiac pacing. Methods: Our analysis included 90 consecutive patients (59% males; average age: 73.2 ± 11.2 years) examined between May 2019−December 2020, with valid 2D and 3D loops for further speckle-tracking strain analysis. Linear regression, Pearson correlation, and a Bland−Altman plot were used to quantify the association between 2D and 3D GLS and related segments, using the 17-segment American Heart Association (AHA) model. Analyses were performed in the entire study group and subgroups. Intra- and inter-observer variability of 2D and 3D GLS measurement was also performed in all participants. Results: We observed a strong correlation between 2D and 3D GLS measurements (R = 0.76, p < 0.001), which was higher in males (R = 0.78, p < 0.001) than females (R = 0.69, p < 0.001). Associated segment correlation was poor (R = 0.2−0.5, p < 0.01). The correlation between 2D and 3D GLS was weaker in individuals with ventricular pacing of >50% (R = 0.62, p < 0.001) than <50% (R = 0.8, p < 0.001), and in patients with LVEF of <35% (R = 0.69, p = 0.002) than >35% (R = 0.72, p < 0.001). Intra-observer variability for 2D and 3D GLS was 2 and 2.3%, respectively. Inter-observer variability for 2D and 3D GLS was 3.8 and 3.6%, respectively Conclusion: Overall 2D and 3D GLS were closely associated but not when analyzed per segment. It seems that GLS comparison is more representative of global shortening than local displacement. Right ventricular pacing and reduced left ventricular ejection fraction were associated with a reduced correlation between 2D and 3D GLS.

Combined Targeted and Untargeted Profiling of HeLa Cells Deficient in Purine De Novo Synthesis.

Three genetically determined enzyme defects of purine de novo synthesis (PDNS) have been identified so far in humans: adenylosuccinate lyase (ADSL) deficiency, 5-amino-4-imidazole carboxamide-ribosiduria (AICA-ribosiduria), and deficiency in bifunctional enzyme phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazolesuccinocarboxamide synthase (PAICS). Clinical signs of these defects are mainly neurological, such as seizures, psychomotor retardation, epilepsy, autistic features, etc. This work aims to describe the metabolic changes of CRISPR-Cas9 genome-edited HeLa cells deficient in the individual steps of PDNS to better understand known and potential defects of the pathway in humans. High-performance liquid chromatography coupled with mass spectrometry was used for both targeted and untargeted metabolomic analyses. The statistically significant features from the untargeted study were identified by fragmentation analysis. Data from the targeted analysis were processed in Cytoscape software to visualize the most affected metabolic pathways. Statistical significance of PDNS intermediates preceding deficient enzymes was the highest (p-values 10 × 10-7-10 × 10-15) in comparison with the metabolites from other pathways (p-values of up to 10 × 10-7). Disturbed PDNS resulted in an altered pool of adenine and guanine nucleotides. However, the adenylate energy charge was not different from controls. Different profiles of acylcarnitines observed among deficient cell lines might be associated with a specific enzyme deficiency rather than global changes related to the PDNS pathway. Changes detected in one-carbon metabolism might reduce the methylation activity of the deficient cells, thus affecting the modification state of DNA, RNA, and proteins.

Hypertension outcomes of adrenalectomy for unilateral primary aldosteronism.

PURPOSE: To evaluate laboratory and clinical results after unilateral adrenalectomy in patients with primary aldosteronism (PHA). METHODS: A cross-sectional analysis was performed using data from patients who underwent transperitoneal laparoscopic adrenalectomy for PHA, between January 2008 and December 2019. Surgical indications were based on adrenal venous sampling without ACTH stimulation. Analyses included patient demographics; preoperative clinical, pharmacological, laboratory, and radiological data; and postoperative results assessed after a median of 4 months. Antihypertensive drug use was quantified by estimating the daily defined dose (DDD) of antihypertensive medication, thus enabling standardized comparison of dosage between the drug classes. Statistical assessments included univariable and multivariable logistic regression analysis. RESULTS: This study enrolled 87 patients. The patients were taking 5.4 DDD of antihypertensive medication before surgery, and 3.0 DDD after surgery. Complete biochemical success of surgery was reached 67 patients (77%), 19 patients (22%) had partial biochemical success. Complete clinical success with normalization of blood pressure and withdrawal of all antihypertensive drugs was achieved in 19 patients (22%). 57 patients (65%) exhibited a reduction of DDD after surgery and/or improvement of blood pressure-partial clinical success. Thus, in 76 (87%) of all enrolled patients, surgery had an overall positive effect on hypertension control. Multivariable logistic regression showed that complete clinical success was independently associated with female gender and baseline sum of antihypertensive drugs DDD < 4. CONCLUSION: A majority of patients undergoing unilateral adrenalectomy for PHA achieved markedly improved hypertension control, despite almost halving their antihypertensive medication. Almost a quarter of patients were cured and able to cease using all antihypertensive drugs.

COVID-19 associated coagulopathy: Mechanisms and host-directed treatment.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is associated with specific coagulopathy that frequently occurs during the different phases of coronavirus disease 2019 (COVID-19) and can result in thrombotic complications and/or death. This COVID-19-associated coagulopathy (CAC) exhibits some of the features associated with thrombotic microangiopathy, particularly complement-mediated hemolytic-uremic syndrome. In some cases, due to the anti-phospholipid antibodies, CAC resembles catastrophic anti-phospholipid syndrome. In other patients, it exhibits features of hemophagocytic syndrome. CAC is mainly identified by: increases in fibrinogen, D-dimers, and von Willebrand factor (released from activated endothelial cells), consumption of a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13 (ADAMTS13), over activated and dysregulated complement, and elevated plasma cytokine levels. CAC manifests as both major cardiovascular and/or cerebrovascular events and dysfunctional microcirculation, which leads to multiple organ damage. It is not clear whether the mainstay of COVID-19 is complement overactivation, cytokine/chemokine activation, or a combination of these activities. Available data have suggested that non-critically ill hospitalized patients should be administered full-dose heparin. In critically ill, full dose heparin treatment is discouraged due to higher mortality rate. In addition to anti-coagulation, four different host-directed therapeutic pathways have recently emerged that influence CAC: (1) Anti-von Willebrand factor monoclonal antibodies; (2) activated complement C5a inhibitors; (3) recombinant ADAMTS13; and (4) Interleukin (IL)-1 and IL-6 antibodies. Moreover, neutralizing monoclonal antibodies against the virus surface protein have been tested. However, the role of antiplatelet treatment remains unclear for patients with COVID-19.