Hypercapnic Chemosensitivity in Patients with Heart Failure: Relation to Shifts in Type-1 Insulin-Like Growth Factor and Sex Hormone-Binding Globulin Levels

In patients suffering from heart failure (HF), autonomic imbalance develops even at early stages along with derangements of cardiopulmonary reflex control and abnormalities in metabolism of several hormones. In 34 men with stable systolic HF, we investigated hypercapnic chemosensitivity (HCS, liter/min·mm Hg) measured using the rebreathing method and defined as the slope of the regression line relating minute ventilation (VE, liter/min) to end­tidal carbon dioxide concentration (PETCO₂ , mm Hg). Serum levels of testosterone, dehydroepiandrosterone sulfate, type­1 insulin­like growth factor (IGF­1), sex hormonebinding globulin (SHBG), estradiol, and cortisol were measured using immunoassays. We found that there were no associations between HCS and clinical variables, applied therapy, and co­morbidities (all P > 0.2). Augmented HCS was accompanied by increased serum SHBG (when expressed in nM, r = 0.43, P < 0.05; when expressed as percentage of the agematched reference values, r = 0.62, P < 0.001) and the reduced serum IGF­1 (when expressed in ng/ml and as percentage of the above­mentioned values, r = –0.49, P < 0.05, and r = = –0.47, P = 0.007, respectively). The HCS was not related to serum levels of all the remaining analyzed hormones (all P > 0.2). Thus, it may be suggested that the hormone stimuli can noticeably modify the reflex mechanisms in cardiorespiratory control in the clinical setting of cardiovascular pathology.У пацієнтів із серцевою недостатністю (СН) навіть на ранніх стадіях захворювання розвивається автономний дисбаланс паралельно з розладами контролю серцево­судинної системи та відхиленнями метаболізму деяких гормонів від норми. Ми досліджували хемочутливість до гіперкапнії (HCS) у 34 чоловіків із СН, використовуючи метод зворотного дихання. Така чутливість визначалась як нахил лінії регресії при співставленні хвилинного об’єму вентиляції (л/хв) та кінцевої концентрації двооксиду вуглецю (мм рт. ст.). Рівні тестостерону, дигідроепіандростерону сульфату, інсулінподібного фактора росту типу 1 (IGF­1), глобуліну, що зв’язує статеві гормони (SHBG), естрадіолу та кортизолу визначали в сироватці крові, використовуючи імунологічні методики. Як виявилося, зв’язки між рівнем HCS, з одного боку, та клінічними показниками, застосованою терапією та супутніми захворюваннями – з другого, були відсутніми (в усіх випадках P > 0.2). Підвищена HCS супроводжувалася підвищеними рівнями SHBG (для концентрацій у наномолях на 1 л r = 0.43, P < 0.05, а для нормованих значень, наведених щодо певної вікової групи, r = 0.62, P < 0.001) та низькими рівнями IGF­1 (для концентрацій у нанограмах на 1 мл та для наведених нормованих значень r = –0.49, P < 0.05 та r = –0.47, P = 0.007 відповідно). Значення HCS не виявляли будь­яких зв’язків з рівнями всіх досліджених гормонів у сироватці. Це дозволяє думати, що гормональні стимули можуть помітно модифікувати рефлекторні механізми контролю серцево­судинної системи у клінічних випадках її патологій

Pre-Transplant Immune Regulation Due to Fetal and Maternal Antigen Exposure

Tumorimmunolog

Effect of short-term rapid ventricular pacing followed by pacing interruption on arterial blood pressure in healthy pigs and pigs with tachycardiomyopathy

Ventricular tachycardia may lead to haemodynamic deterioration and, in the case of long term persistence, is associated with the development of tachycardiomyopathy. The effect of ventricular tachycardia on haemodynamics in individuals with tachycardiomyopathy, but being in sinus rhythm has not been studied. Rapid ventricular pacing is a model of ventricular tachycardia. The aim of this study was to determine the effect of rapid ventricular pacing on blood pressure in healthy animals and those with tachycardiomyopathy. A total of 66 animals were studied: 32 in the control group and 34 in the study group. The results of two groups of examinations were compared: the first performed in healthy animals (133 examinations) and the second performed in animals paced for at least one month (77 examinations). Blood pressure measurements were taken during chronic pacing - 20 min after onset of general anaesthesia, in baseline conditions (20 min after pacing cessation or 20 min after onset of general anaesthesia in healthy animals) and immediately after short-term rapid pacing. In baseline conditions significantly higher systolic and diastolic blood pressure was found in healthy animals than in those with tachycardiomyopathy. During an event of rapid ventricular pacing, a significant decrease in systolic and diastolic blood pressure was found in both groups of animals. In the group of chronically paced animals the blood pressure was lower just after restarting ventricular pacing than during chronic pacing. Cardiovascular adaptation to ventricular tachycardia develops with the length of its duration. Relapse of ventricular tachycardia leads to a blood pressure decrease more pronounced than during chronic ventricular pacing

Responder analysis for improvement in 6-min walk test with ferric carboxymaltose in patients with heart failure with reduced ejection fraction and iron deficiency

Aim: Improving functional capacity is a key goal in heart failure (HF). This pooled analysis of FAIR-HF and CONFIRM-HF assessed the likelihood of improvement or deterioration in 6-min walk test (6MWT) among iron-deficient patients with chronic HF with reduced ejection fraction (HFrEF) receiving ferric carboxymaltose (FCM). Methods and results: Data for 760 patients (FCM: n = 454; placebo: n = 306) were analysed. The proportions of patients receiving FCM or placebo who had ≥20, ≥30, and ≥40 m improvements or ≥10 m deterioration in 6MWT at 12 and 24 weeks were assessed. Patients receiving FCM experienced a mean (standard deviation) 31.1 (62.3) m improvement in 6MWT versus 0.1 (77.1) m improvement for placebo at week 12 (difference in mean changes 26.8 [16.6–37.0]). At week 12, the odds [95% confidence interval] of 6MWT improvements of ≥20 m (odds ratio 2.16 [1.57–2.96]; p &lt; 0.0001), ≥30 m (2.00 [1.44–2.78]; p &lt; 0.0001), and ≥40 m (2.29 [1.60–3.27]; p &lt; 0.0001) were greater with FCM versus placebo, while the odds of a deterioration ≥10 m were reduced with FCM versus placebo (0.55 [0.38–0.80]; p = 0.0019). Among patients who experienced 6MWT improvements of ≥20, ≥30, or ≥40 m with FCM at week 12, more than 80% sustained this improvement at week 24. Conclusion: Ferric carboxymaltose resulted in a significantly higher likelihood of improvement and a reduced likelihood of deterioration in 6MWT versus placebo among iron-deficient patients with HF. Of the patients experiencing clinically significant improvements at week 12, the majority sustained this improvement at week 24. These results are supportive of FCM to improve exercise capacity in HF. © 2022 The Authors. European Journal of Heart Failure published by John Wiley &amp; Sons Ltd on behalf of European Society of Cardiology

Rationale and design of the AFFIRM-AHF trial: a randomised, double-blind, placebo-controlled trial comparing the effect of intravenous ferric carboxymaltose on hospitalisations and mortality in iron-deficient patients admitted for acute heart failure

Aims: Iron deficiency (ID) is a common co-morbidity in heart failure (HF), associated with impaired functional capacity, poor quality of life and increased morbidity and mortality. Treatment with intravenous (i.v.) ferric carboxymaltose (FCM) has shown improvements in functional capacity, symptoms and quality of life in stable HF patients with reduced ejection fraction. The effect of i.v. iron supplementation on morbidity and mortality in patients hospitalised for acute HF (AHF) and who have ID has yet to be established. The objective of the present article is to present the rationale and design of the AFFIRM-AHF trial (ClinicalTrials.gov NCT02937454) which will investigate the effect of i.v. FCM (vs. placebo) on recurrent HF hospitalisations and cardiovascular (CV) mortality in iron-deficient patients hospitalised for AHF. Methods: AFFIRM-AHF is a multicentre, randomised (1:1), double-blind, placebo-controlled trial which recruited 1100 patients hospitalised for AHF and who had iron deficiency ID defined as serum ferritin &lt;100 ng/mL or 100–299 ng/mL if transferrin saturation &lt;20%. Eligible patients were randomised (1:1) to either i.v. FCM or placebo and received the first dose of study treatment just prior to discharge for the index hospitalisation. Patients will be followed for 52 weeks. The primary outcome is the composite of recurrent HF hospitalisations and CV mortality. The main secondary outcomes include the composite of recurrent CV hospitalisations and CV mortality, recurrent HF hospitalisations and safety-related outcomes. Conclusion: The AFFIRM-AHF trial will evaluate, compared to placebo, the effect of i.v. FCM on morbidity and mortality in iron-deficient patients hospitalised for AHF. © 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiolog

Clinical practice update on heart failure 2019: pharmacotherapy, procedures, devices and patient management. An expert consensus meeting report of the Heart Failure Association of the European Society of Cardiology

The European Society of Cardiology (ESC) has published a series of guidelines on heart failure (HF) over the last 25 years, most recently in 2016. Given the amount of new information that has become available since then, the Heart Failure Association (HFA) of the ESC recognized the need to review and summarise recent developments in a consensus document. Here we report from the HFA workshop that was held in January 2019 in Frankfurt, Germany. This expert consensus report is neither a guideline update nor a position statement, but rather a summary and consensus view in the form of consensus recommendations. The report describes how these guidance statements are supported by evidence, it makes some practical comments, and it highlights new research areas and how progress might change the clinical management of HF. We have avoided re-interpretation of information already considered in the 2016 ESC/HFA guidelines. Specific new recommendations have been made based on the evidence from major trials published since 2016, including sodium–glucose co-transporter 2 inhibitors in type 2 diabetes mellitus, MitraClip for functional mitral regurgitation, atrial fibrillation ablation in HF, tafamidis in cardiac transthyretin amyloidosis, rivaroxaban in HF, implantable cardioverter-defibrillators in non-ischaemic HF, and telemedicine for HF. In addition, new trial evidence from smaller trials and updated meta-analyses have given us the chance to provide refined recommendations in selected other areas. Further, new trial evidence is due in many of these areas and others over the next 2 years, in time for the planned 2021 ESC guidelines on the diagnosis and treatment of acute and chronic heart failure. © 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiolog

Patient profiling in heart failure for tailoring medical therapy. A consensus document of the Heart Failure Association of the European Society of Cardiology

Despite guideline recommendations and available evidence, implementation of treatment in heart failure (HF) is poor. The majority of patients are not prescribed drugs at target doses that have been proven to positively impact morbidity and mortality. Among others, tolerability issues related to low blood pressure, heart rate, impaired renal function or hyperkalaemia are responsible. Chronic kidney disease plays an important role as it affects up to 50% of patients with HF. Also, dynamic changes in estimated glomerular filtration rate may occur during the course of HF, resulting in inappropriate dose reduction or even discontinuation of decongestive or neurohormonal modulating therapy in clinical practice. As patients with HF are rarely naïve to pharmacologic therapies, the challenge is to adequately prioritize or select the most appropriate up-titration schedule according to patient profile. In this consensus document, we identified nine patient profiles that may be relevant for treatment implementation in HF patients with a reduced ejection fraction. These profiles take into account heart rate (&amp;lt;60 bpm or &amp;gt;70 bpm), the presence of atrial fibrillation, symptomatic low blood pressure, estimated glomerular filtration rate (&amp;lt;30 or &amp;gt;30 mL/min/1.73 m2) or hyperkalaemia. The pre-discharge patient, frequently still congestive, is also addressed. A personalized approach, adjusting guideline-directed medical therapy to patient profile, may allow to achieve a better and more comprehensive therapy for each individual patient than the more traditional, forced titration of each drug class before initiating treatment with the next. © 2021 European Society of Cardiolog

The autonomic nervous system as a therapeutic target in heart failure: a scientific position statement from the Translational Research Committee of the Heart Failure Association of the European Society of Cardiology

Despite improvements in medical therapy and device-based treatment, heart failure (HF) continues to impose enormous burdens on patients and health care systems worldwide. Alterations in autonomic nervous system (ANS) activity contribute to cardiac disease progression, and the recent development of invasive techniques and electrical stimulation devices has opened new avenues for specific targeting of the sympathetic and parasympathetic branches of the ANS. The Heart Failure Association of the European Society of Cardiology recently organized an expert workshop which brought together clinicians, trialists and basic scientists to discuss the ANS as a therapeutic target in HF. The questions addressed were: (i) What are the abnormalities of ANS in HF patients? (ii) What methods are available to measure autonomic dysfunction? (iii) What therapeutic interventions are available to target the ANS in patients with HF, and what are their specific strengths and weaknesses? (iv) What have we learned from previous ANS trials? (v) How should we proceed in the future?. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiolog