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

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

Proteomic Profiling of Dilated Cardiomyopathy Plasma Samples ─ Searching for Biomarkers with Potential to Predict the Outcome of Therapy.

Determination of the prognosis and treatment outcomes of dilated cardiomyopathy is a serious problem due to the lack of valid specific protein markers. Using in-depth proteome discovery analysis, we compared 49 plasma samples from patients suffering from dilated cardiomyopathy with plasma samples from their healthy counterparts. In total, we identified 97 proteins exhibiting statistically significant dysregulation in diseased plasma samples. The functional enrichment analysis of differentially expressed proteins uncovered dysregulation in biological processes like inflammatory response, wound healing, complement cascade, blood coagulation, and lipid metabolism in dilated cardiomyopathy patients. The same proteome approach was employed in order to find protein markers whose expression differs between the patients well-responding to therapy and nonresponders. In this case, 45 plasma proteins revealed statistically significant different expression between these two groups. Of them, fructose-1,6-bisphosphate aldolase seems to be a promising biomarker candidate because it accumulates in plasma samples obtained from patients with insufficient treatment response and with worse or fatal outcome. Data are available via ProteomeXchange with the identifier PXD046288.

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.

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.

Angiotensin-converting enzyme inhibitors, angiotensin-II-receptor antagonists and angiotensin-receptor blocker/neprilysin inhibitor utilization in heart failure patients: Sub-analysis of a nation-wide population-based study in the Czech Republic.

AIMS: Sub-analysis of a retrospective nation-wide observational analysis of heart failure (HF) epidemiology reported to the Czech National Registry of Reimbursed Health Services between 2012 and 2018 aimed at angiotensin-converting enzyme inhibitors (ACEI), angiotensin-II-receptor antagonists (ARB) and angiotensin receptor blocker/neprilysin inhibitor (ARNI) use. METHODS AND RESULTS: ACEi and ARBs were generally used in 87.6% of all HF patients in 2012 (n=154 627); 84.5% in 2013 (n=170 861); 83.5% in 2014 (n=186 963); 81.6% in 2015 (n=198 844); 80.1% in 2016 (n=205 793); 78.0% in 2017 (n=212 152) and in 76.7% in 2018 (n=219 235). In a sub-analysis of patients with a medical procedure and/or examination using an I50.x ICD code accounted for in the given year, ACEi and ARBs were generally used in 99.3% in 2012 (n=63 250); 96% in 2013 (n=62 241); 95.2% in 2014 (n=64 414); 93.3% in 2015 (n=65 217); 91.8% in 2016 (n=65 236); 90.1% in 2017 (n=65 761) and in 88.6% in 2018 (n=66 332). In 2018, the majority of patients with HF were prescribed ramipril (n=49 909; 17.5%) and perindopril (n=44 332; 15.5%). The mostly prescribed ARBs in 2018 were telmisartan (n=18 669; 6.5%); losartan (n=13 935; 4.9%) and valsartan (n=4 849; 1.7%). In 24.5% of cases, ACEIs and ARBs were prescribed in a fixed combination with another drug. ARNI became gradually more prescribed from 2018 (n=9 659 in November 2020). CONCLUSION: In an analysis of ACEIs, ARBs and ARNIs utilization in all patients treated for heart failure in the given year in the whole country, we found a comparable rate of drug prescription in comparison with specific heart failure registries. This indicates a good translation of current standard of care into common clinical practice. Ramipril and perindopril remained the mostly prescribed ACEIs and telmisartan became the mostly prescribed ARB. Since 2018, ARNIs began to be widely prescribed.

Trends in the treatment and survival of heart failure patients: a nationwide population-based study in the Czech Republic.

AIMS: A retrospective nationwide observational analysis of diagnoses, procedures, and treatment reported to the Czech National Registry of Reimbursed Health Services between 2012 and 2018. METHODS AND RESULTS: Prevalence of heart failure (HF) patients increased from 176 496 (1679.4 per 100 000 population) in 2012 to 285 745 (2689.0 per 100 000 population) patients in 2018 (mean age 74.4 ± 12.8 years). In the last years, a stable incidence of HF patients was observed (544 per 100 000 population in 2016 vs. 551 per 100 000 population in 2018; P = 0.310). Mortality rate decreased from 20.55% in 2012 to 15.89% in 2018. The number of hospitalized patients remained similar (318.2 per 100 000 population in 2012 vs. 311.8 per 100 000 population in 2018; P = 0.479). The most used drugs were diuretics (173 295; 60.6%) and beta-blockers (178 823; 62.6%), followed by angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (angiotensin-converting enzyme inhibitors 120.581; 42.2%; angiotensin II receptor blockers 47 216; 16.5%). Even though the whole number of implanted devices in HF patients increased steadily (from 25 205 in 2012 to 45 363 in 2018), the prevalence of all devices (pacemakers and defibrillators) in the HF patients remained about the same (14.3% in 2012; 15.9% in 2018). CONCLUSIONS: The study included all patients with HF in the Czech Republic. These are the first nationwide data of HF epidemiology in the Eastern bloc. The incidence of HF remains stable in the last years. Due to aging of the population, the prevalence of HF significantly increased in the last 6 years. Despite a continuous increase in the prevalence of HF and a suboptimal utilization of its pharmacological therapy, mortality decreased, and the number of hospitalized patients remained the same.

Directly Measured Adherence to Treatment in Chronic Heart Failure: LEVEL-CHF Registry.

BACKGROUND: Currently, most available data on the medication adherence of patients with chronic heart failure are based on indirect methods. We examined the level of adherence to medical therapy using a direct method - serum drug level testing. METHODS: We carried out a prospective single-centre registry of patients with chronic heart failure (LEVEL-CHF registry), in whom we analysed serum levels of the medications prescribed for the treatment of heart failure: angiotensin converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists. We labelled a patient as non-adherent if at least one serum level of a prescribed drug was unmeasurable (below the detection limit). Patients with all tested drugs identifiable in serum were labelled as adherent. We enrolled 274 patients (208 men and 66 women) mean age 62 years. RESULTS: 82.5% of patients were adherent and 17.5% non-adherent to prescribed medications. 3.6% were completely non-adherent without any detectable drugs in serum. Patients aged <60 years were more likely to be non-adherent than older patients (OR 2.15). No other clinical or laboratory parameters predicted non-adherence. CONCLUSIONS: A significant proportion of outpatients with chronic heart failure were non-adherent to treatment when assessed by a direct method of serum drug level testing. Non-adherence was more likely in younger patients.

Beta-blockers utilization in heart failure patients: Sub-analysis of a nation-wide population-based study in the Czech Republic.

AIMS: Sub-analysis of a retrospective nation-wide observational analysis of heart failure (HF) epidemiology reported to the Czech National Registry of Reimbursed Health Services between 2012 and 2018 aimed at beta-blockers (BBs) utilization. METHODS AND RESULTS: The beta-blockers were generally used in 81.8% of all patients treated for HF in 2012 (n=52 140); 81.8% in 2013 (n=53 058); 83.1% in 2014 (n=56 221); 82.1% in 2015 (n=57 421); 83.3% in 2016 (n=59 187); 82.2% in 2017 (60 058) and in 81.4% in 2018 (n=60 966). In 2018, the majority of patients treated for HF were prescribed metoprolol (22 974; 30.7%) and bisoprolol (21 001; 28%). Carvedilol was prescribed in 7 331 patients treated for HF (9.8%), nebivolol in 5 392 HF patients. Despite its primary indication, betaxolol was used in 2 341 patients treated for HF (3.1%). All other beta-blockers were used in less than 1% of HF patients. In some of the mostly used BBs, their prescription in patients treated for HF changed in the last years (metoprolol 32.4% in 2012, 30.7% in 2018; bisoprolol 20.3% in 2012, 28% in 2018; carvedilol 18.3% in 2012, 9.8% in 2018; nebivolol 2.5% in 2012, 7.2% in 2018; betaxolol 4.2% in 2012, 3.1% in 2018). CONCLUSION: In an analysis of beta-blockers utilization in all patients treated for heart failure in the given year in the whole country, we have found only slightly lower amount of drug prescription in comparison with specific heart failure registries. This indicates a good translation of current standard of care into common clinical practice. Metoprolol remained the mostly prescribed drug. The prescription of bisoprolol and nebivolol has increased at the expense of carvedilol.

Heart failure disease management program, its contribution to established pharmacotherapy and long-term prognosis in real clinical practice - retrospective data analysis.

BACKGROUND AND AIMS: The prognosis of patients with heart failure (HF) is still generally unfavorable. HF with reduced ejection fraction (HFrEF) patients reach target medication doses in very low percentages in daily clinical practice. HF disease management programs (DMP), including nurse and telemedicine support that facilitate achieving target medication doses, may improve the unfavorable prognosis. METHODS: We retrospectively analyzed the data of 738 patients with HFrEF who were followed in a single HF center during the years 1975-2011, for 6.4 (median) years. DMP, nurse and telemedicine support is established at this center. RESULTS: The group achieved left ventricle (LV) recovery after the HF treatment. The median LV ejection fraction improved from 25.0% at baseline to 50.0% at the time of the latest data collection. The proportion of NYHA II, III and IV classes decreased from 27.6%, 30.2% and 29.7% to 26.6%, 7.2% and 0.1%, respectively while the proportion of NYHA class I increased from 12.5% to 66.1%. Median NT-proBNP decreased from 975.0 to 324.0 pg/mL. The survival of the patient group was favorable; 79.7% survived 18.1 years after diagnosis of HF. A high percentage of the patients received recommended target or higher than target doses of angiotensin-converting enzyme inhibitors (82.0%) and beta-blockers (78.1%). CONCLUSION: The established pharmacotherapy resulted from an effective DMP and this contributed to the favorable prognosis.

[Palliative care in cardiology]. / Paliativní péce v kardiologii.

Chronic heart failure is a progressive disease with an increasing prevalence. In spite of all medical progress (or thanks to it), it is finally one of the most common causes of death. Palliative care is an approach aimed to improve the quality of life of patients and their families in cases of life-threatening illness. Therefore, the use of palliative care in cardiology is entirely relevant. Estimating the course and prognosis of a patient with chronic heart failure is difficult despite many prognostic tools. This makes it difficult to find the moment when palliative care is to begin. In general, gradual accentuation of treatment is recommended, focusing on the symptoms of the chronic progressive disease trajectory, and a reassessment of the benefit and potential adverse effects of conventional therapy. The main aspects of palliative care in cardiology are: 1. long-term communication with the patient and the family and their continuous education; 2. symptom-based treatment; 3. planning of advanced care; 4. A multidisciplinary team trying to meet all the patient's personality needs. Accepting palliative care as a part of complex care is a great challenge for the future of cardiology in the Czech Republic.Key words: heart failure, palliative care, cardiology.

Proteomic biomarkers of recovered heart function.

AIMS: Chronic heart failure is a costly epidemic that affects up to 2% of people in developed countries. The purpose of this study was to discover novel blood proteomic biomarker signatures of recovered heart function that could lead to more effective heart failure patient management by both primary care and specialty physicians. METHODS AND RESULTS: The discovery cohort included 41 heart transplant patients and 20 healthy individuals. Plasma levels of 138 proteins were detected in at least 75% of these subjects by iTRAQ mass spectrometry. Eighteen proteins were identified that had (i) differential levels between pre-transplant patients with end-stage heart failure and healthy individuals; and (ii) levels that returned to normal by 1 month post-transplant in patients with stable heart function after transplantation. Seventeen of the 18 markers were validated by multiple reaction monitoring mass spectrometry in a cohort of 39 heart failure patients treated with drug therapy, of which 30 had recovered heart function and 9 had not. This 17-protein biomarker panel had 93% sensitivity and 89% specificity, while the RAMP® NT-proBNP assay had the same specificity but 80% sensitivity. Performance further improved when the panel was combined with NT-proBNP, yielding a net reclassification index relative to NT-proBNP of 0.28. CONCLUSIONS: We have identified potential blood biomarkers of recovered heart function by harnessing data from transplant patients. These biomarkers can lead to the development of an inexpensive protein-based blood test that could be used by physicians to monitor response to therapy in heart failure, resulting in more personalized, front-line heart failure patient management.

Free plasma metanephrines as a screening test for pheochromocytoma in low-risk patients.

OBJECTIVES: Detection of free plasma metanephrines seems to be the most exact method for biochemical diagnosis of pheochromocytoma, but their diagnostic efficacy in the common low-risk clinical settings is debated. METHODS: A cross-sectional multicentre study including 1260 subjects assessed the diagnostic efficacy of free plasma metanephrine and normetanephrine in low-risk patients screened for resistant or markedly accelerated hypertension, paroxysmal hypertension, 'flushes' and, in a small proportion, for adrenal incidentaloma or genetic predisposition to pheochromocytoma. RESULTS: Pheochromocytoma was identified and verified by histology in 25 subjects (2%), with the diagnosis not confirmed by long-term follow-up or use of imaging techniques in the remaining 1235 individuals. The combined assay of free plasma metanephrines was a highly sensitive (100%) and specific (96.7%) measure, yielding a negative predictive value of 100%. CONCLUSION: The satisfactory diagnostic efficacy of free plasma metanephrines allows their use as a single screening test in cases of suspected pheochromocytoma in the population with a low pretest probability.

The antioxidant acetylcysteine reduces oxidative stress by decreasing level of AOPPs.

Oxidative stress and especially its connection with many diseases has been discussed much recently. Among markers of oxidative stress there appear new and quite specific ones called advanced oxidation protein products (AOPPs). We tried to influence the level of AOPPs by an antioxidant therapy with N-acetylcysteine. Fourteen individuals with many cardiovascular risk factors were examined. All these patients were administered acetylcysteine (NAC) 600 mg/day orally during 20 days. Before starting the therapy we determined AOPP, albumin cobalt binding (ACB), glucose, creatinine, urea, ALT, AST, cholesterol, LDL, HDL and triglycerides values in peripheral venous blood in all individuals. After finishing our intervention we determined AOPP, ACB and glucose level again. Our results show a statistically significant decrease in AOPP levels after 20-day N-acetylcysteine therapy (medians, initially 82.2, at study end 74.3 umol/l, p = 0.039). We demonstrate a significant decrease in AOPP levels after 20-day N-acetylcysteine therapy in dose 600 mg/day.