Aim: The aim of this article is to investigate and describe the coping strategies of elderly widows. Theoretical base: The grieving process is well described in the literature. However, in real life, it is always necessary to respect the uniqueness of the process for each individual. Most previous studies have focused on difficulties of the bereaved and their risk of dying. More recently, the strengths of the bereaved and how they develop have also been emphasised. A dual-proces model of coping with bereavement was used. It is based on loss-oriented and restoration-oriented strategies and the oscillation between them. In the Czech context, there is a lack of research based on this dual-process model describing coping strategies after the loss of a loved one. Methods: The paper presents the results of ethically demanding research using semi-structured interviews with 15 elderly widows. The authors based the model on a questionnaire survey using a qualitative methodology because of the aspiration to describe the strategies of individual women in detail. Results: The output is a description of coping strategies, categorized into loss- and recovery-oriented approaches, used by elderly women to navigate the period following their partner's death. Conclusion: Describing how the women interviewed have coped with their challenging life situation could inspire not only other elderly women but also their relatives and aid workers who come into contact with this target group.

• MeSH
• Adaptation, Psychological MeSH
• Coping Skills * methods   MeSH
• Qualitative Research MeSH
• Humans MeSH
• Spouses psychology   MeSH
• Interviews as Topic MeSH
• Aged MeSH
• Death MeSH
• Widowhood psychology   MeSH
• Grief MeSH
• Self Report MeSH
• Bereavement * MeSH
• Check Tag
• Humans MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH

BACKGROUND: Chronic thromboembolic pulmonary hypertension results from mechanical obstruction of major pulmonary artery lumina with fibrotic tissue. Main treatment has been pulmonary endarterectomy, a complex surgical procedure removing vascular obstruction. However, at least 40% of patients are not candidates for pulmonary endarterectomy because of technical inoperability, comorbidities, or limited access to surgery. Balloon pulmonary angioplasty (BPA) has emerged as an interventional treatment for these patients. OBJECTIVES: The International BPA Registry (NCT03245268) was designed to investigate BPA practice across 18 established centers in the United States, Europe, and Japan. METHODS: A total of 500 patients were prospectively and consecutively enrolled between March 2018 and March 2020, with follow-up until March 2022. Of these, 484 patients were included in the analysis set. RESULTS: Regional differences were seen in patient characteristics (fewer patients with prior pulmonary endarterectomy and more elderly women in Japan) and procedural details (less medical pretreatment, more jugular access, more segments and more occlusive lesions treated per session and patient, less conscious sedation, less contrast and less radiation, shorter intervals between BPA sessions in Japan). Female sex, procedure in Europe/United States, pulmonary hypertension medications at any time, and higher baseline pulmonary vascular resistance (PVR), calculated as transpulmonary pressure gradient divided by cardiac output, emerged as independent predictors of complications during BPA. After a median of 5 (Q1-Q3: 3-6) BPA sessions per patient within a median time of 4.9 months (Q1-Q3: 1.7-11.0 months), a 15-mm Hg (38%) decrease in mPAP, a 332 dynes/s/cm-5 (57%) decrease in PVR, and a 3.2% increase in arterial saturation (medians; P < 0.001) were observed, and there were significant improvements in functional class, 6-minute walk distance, serum levels of N-terminal probrain natriuretic peptide, and Borg dyspnea index. BPA complications occurred in 11.3% of sessions and 33.9% of patients and were mostly hemoptyses. No patient died within 30 days of BPA. CONCLUSIONS: Our data are in line with previous reports on changes of clinical and hemodynamic parameters and complication rates of BPA. Centers with more experience providing BPAs were more likely to achieve a higher percentage decrease in PVR.

• MeSH
• Pulmonary Artery surgery   MeSH
• Angioplasty, Balloon * methods   MeSH
• Chronic Disease MeSH
• Middle Aged MeSH
• Humans MeSH
• Pulmonary Embolism * complications   surgery   MeSH
• Hypertension, Pulmonary * etiology   surgery   therapy   physiopathology   MeSH
• Prospective Studies MeSH
• Registries * MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Geographicals
• Europe MeSH
• Japan MeSH
• United States MeSH

Mitochondria are key to cellular energetics, metabolism, and signaling. Their dysfunction is linked to devastating diseases, including mitochondrial disorders, diabetes, neurodegenerative diseases, cardiac disorders, and cancer. Here, we present a knockout mouse model lacking the complex IV assembly factor SMIM20/MITRAC7. SMIM20-/- mice display cardiac pathology with reduced heart weight and cardiac output. Heart mitochondria present with reduced levels of complex IV associated with increased complex I activity, have altered fatty acid oxidation, and display elevated levels of ROS production. Interestingly, mutant mouse ventricular myocytes show unphysiological Ca2+ handling, which can be attributed to the increase in mitochondrial ROS production. Our study presents an example of a tissue-specific phenotype in the context of OXPHOS dysfunction. Moreover, our data suggest a link between complex IV dysfunction and Ca2+ handling at the endoplasmic reticulum through ROS signaling.

• MeSH
• Endoplasmic Reticulum metabolism   MeSH
• Myocytes, Cardiac metabolism   MeSH
• Membrane Proteins * metabolism   genetics   MeSH
• Mitochondrial Proteins * metabolism   genetics   MeSH
• Myocardium * metabolism   MeSH
• Mice, Inbred C57BL MeSH
• Mice, Knockout MeSH
• Mice MeSH
• Oxidative Phosphorylation MeSH
• Zebrafish Proteins MeSH
• Reactive Oxygen Species metabolism   MeSH
• Electron Transport Complex IV * metabolism   MeSH
• Mitochondria, Heart metabolism   MeSH
• Calcium metabolism   MeSH
• Calcium Signaling * MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

The effects of a large arteriovenous fistula (AVF) on pulmonary perfusion remains to be elucidated. We aimed to study, for the first time, the real-time acute effects of a large AVF on regional distribution of pulmonary perfusion in a novel porcine model. Ten healthy swine under general anesthesia were studied. AVF was created by the connection of femoral artery and femoral vein using high-diameter perfusion cannulas. The AVF was closed and after 30 min of stabilization the first values were recorded. The fistula was then opened, and new data were collected after reaching stable state. Continuous hemodynamic monitoring was performed throughout the protocol. The following functional images were analyzed by electrical impedance tomography (EIT): perfusion and ventilation distributions. We found an increased cardiac output and right ventricular work, which was strongly correlated to an increased pulmonary artery mean pressure (r=0.878, P=0.001). The ventral/dorsal ratio of pulmonary perfusion decreased from 1.9+/-1.0 to 1.5+/-0.7 (P=0.025). The percentage of total pulmonary blood flow through the dorsal lung region increased from 38.6+/-11.7 to 42.2+/-10.4 (P=0.016). In conclusion, we have used EIT for the first time for studying the acute effects of a large AVF on regional distribution of pulmonary perfusion in a novel porcine model. In this new experimental model of hyperkinetic circulation caused by AVF, we documented an increased percentage of total pulmonary blood flow through the dorsal lung region and a more homogeneous perfusion distribution. Key words Arteriovenous fistula, Hyperkinetic circulation, Tissue perfusion, Animal model, Pulmonary blood flow.

• MeSH
• Pulmonary Artery diagnostic imaging   physiopathology   MeSH
• Arteriovenous Fistula physiopathology   diagnostic imaging   MeSH
• Arteriovenous Shunt, Surgical MeSH
• Lung blood supply   diagnostic imaging   MeSH
• Pulmonary Circulation * physiology   MeSH
• Swine MeSH
• Femoral Vein diagnostic imaging   MeSH
• Animals MeSH
• Check Tag
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Creatine is a nitrogen-containing carboxylic acid and a main component of phosphocreatine. In recent years, creatine is considered as a component of dietary nutrition, to improve the efficiency of physical activity and increase muscle mass of athletes and older people. Creatine has been shown to be able restore cardiac contractility impairment after myocardial infarction. However, as muscle cells do not synthesise creatine, the efficiency of creatine depends on its transmembrane transport. In our study, we evaluated the effect of «ProCreatine» (ProCr), a novel membrane transporter-independent creatine modification on fatigability of the rat gastrocnemius muscle and portal vein smooth muscle using fatigue stimulation pools. Mechanokinetic and biomechanical markers of fatigue in muscles to maintain the level of isometric tension induced by field electrical stimulation were examined. The results indicate that administration of ProCr to skeletal muscle significantly increases maximal force output, integrated muscle contractile force and significantly increases muscle productivity. We observed positive changes in all studied biochemical indices of fatigue. In addition, ProCr increases the duration of sustaining a constant level of isometric contraction in portal vein smooth muscle caused by electrical stimulation by 6 fold. Regular creatine in the same dose had no significant effect on these parameters neither in skeletal nor in smooth muscles. The data obtained suggest the possibility of using ProCr as a therapeutic agent capable of reducing and correcting pathological conditions of the muscular system that arise during the processes of fatigue in skeletal muscles and smooth muscles of hollow organs.

• Publication type
• Journal Article MeSH

• MeSH
• Anesthesia MeSH
• Physical Phenomena MeSH
• Critical Care MeSH

Cardiovascular diseases represent an economic burden for health systems accounting for substantial morbidity and mortality worldwide. Despite timely and costly efforts in drug development, the cardiovascular safety and efficacy of the drugs are not always fully achieved. These lead to the drugs' withdrawal with adverse cardiac effects from the market or in the late stages of drug development. There is a growing need for a cost-effective drug screening assay to rapidly detect potential acute drug cardiotoxicity. The Langendorff isolated heart perfusion technique, which provides cardiac hemodynamic parameters (e.g., contractile function and heart rate), has become a powerful approach in the early drug discovery phase to overcome drawbacks in the drug candidate's identification. However, traditional ex vivo retrograde heart perfusion methods consume a large volume of perfusate, which increases the cost and limits compound screening. An elegant and cost-effective alternative mode for ex vivo retrograde heart perfusion is the constant-flow with a recirculating circuit (CFCC), which allows assessment of cardiac function using a reduced perfusion volume while limiting adverse effects on the heart. Here, we provide evidence for cardiac parameters stability over time in this mode. Next, we demonstrate that our recycled ex vivo perfusion system and the traditional open one yield similar outputs on cardiac function under basal conditions and upon ?-adrenergic stimulation with isoproterenol. Subsequently, we validate the proof of concept of therapeutic agent screening using this efficient method. ?-blocker (i.e., propranolol) infusion in closed circulation countered the positive effects induced by isoproterenol stimulation on cardiac function. Keywords: Drug development, Drug screening, Cardiovascular safety, Langendorff method, Closed circulation.

• MeSH
• Rats MeSH
• Perfusion * MeSH
• Drug Evaluation, Preclinical * methods   MeSH
• Isolated Heart Preparation * MeSH
• Heart drug effects   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Do vývoja metód na meranie tlaku krvi sa významne zapojili aj pracovníci, ktorí sa narodili na území dnešného Slovenska a Českej republiky: Samuel von Basch (Plzeň) skonštruoval prvý ľahko prenosný sfygmomanometer vhodný na meranie tlaku krvi aj u detí. Gustav Gärtner (Pardubice) svojim tonometrom aplikovaným na prst dal základ flush metóde používanej neskôr na meranie tlaku krvi u detí a novorodencov. Eva Kellerová (Bratislava) zdokonalila ultrazvukovú metódu merania tlaku krvi, ktorá sa stala vhodnou i na merania u novorodencov. Jan Peňáz (Brno) vynašiel originálnu neinvazívnu metódu kontinuálnej beat-to-beat registrácie tlaku krvi v prstových artériách tzv. volume-clamp metódou. Otto Klein (Plzeň) urobil niekoľko mesiacov po pokusoch W. Forssmanna 11 úspešných katetrizácií pravého srdca u pacientov v Prahe, ako prvý s diagnostickým účelom. William Ganz (Košice) spolu s Jeremy Swanom skonštruovali originálny katéter, ktorým sa dá merať tlak krvi v pravej predsieni i komore, v a. pulmonalis, špeciálny tlak (PCWP – Pulmonary Capillary Wedge Pressure), ako aj vývrhový objem srdca termodilučnou metódou. Ako vidieť i z tohto prehľadu, rodáci z územia súčasného Česka a Slovenska významne prispeli k rozvoju neinvazívneho i invazívneho merania tlaku krvi u dospelých ľudí, ako aj u novorodencov a detí.

Researchers who were born in the territories of today‘s Slovakia and the Czech Republic were also significantly involved in the development of methods for measuring blood pressure: Samuel von Basch (Pilsen) constructed the first easily portable sphygmomanometer suitable for measuring blood pressure even in children. Gustav Gärtner (Pardubice), with his finger-applied tonometer, provided the basis for the flush method later used to measure blood pressure in children and newborns. Eva Kellerová (Bratislava) improved the ultrasound method of measuring blood pressure, which has become suitable also for measurements in newborns. Jan Peňáz (Brno) invented a unique non-invasive method of continuous beat-to-beat registration of blood pressure in finger arteries by the so-called volume-clamp method. Otto Klein (Pilsen) performed 11 successful right heart catheterizations on patients in Prague, the first for for diagnostic purposes, only a few months after W. Forssmann‘s experiments. William Ganz (Košice) together with Jeremy Swan constructed an original catheter that can measure blood pressure in the right atrium and ventricle, a.pulmonalis, special pressure (PCWP - Pulmonary Capillary Wedge Pressure), as well as cardiac output by thermodilution method. As can be seen from this review, natives of the territory of the present-day Czech Republic and Slovakia have contributed significantly to the development of non-invasive and invasive blood pressure measurement in adult humans as well as in neonates and children.

IMPORTANCE: Impaired exercise capacity is a cardinal manifestation of obstructive hypertrophic cardiomyopathy (HCM). The Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic Obstructive HCM (SEQUOIA-HCM) is a pivotal study characterizing the treatment effect of aficamten, a next-in-class cardiac myosin inhibitor, on a comprehensive set of exercise performance and clinical measures. OBJECTIVE: To evaluate the effect of aficamten on exercise performance using cardiopulmonary exercise testing with a novel integrated measure of maximal and submaximal exercise performance and evaluate other exercise measures and clinical correlates. DESIGN, SETTING, AND PARTICIPANTS: This was a prespecified analysis from SEQUOIA-HCM, a double-blind, placebo-controlled, randomized clinical trial. Patients were recruited from 101 sites in 14 countries (North America, Europe, Israel, and China). Individuals with symptomatic obstructive HCM with objective exertional intolerance (peak oxygen uptake [pVO2] ≤90% predicted) were included in the analysis. Data were analyzed from January to March 2024. INTERVENTIONS: Randomized 1:1 to aficamten (5-20 mg daily) or matching placebo for 24 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was change from baseline to week 24 in integrated exercise performance, defined as the 2-component z score of pVO2 and ventilatory efficiency throughout exercise (minute ventilation [VE]/carbon dioxide output [VCO2] slope). Response rates for achieving clinically meaningful thresholds for change in pVO2 and correlations with clinical measures of treatment effect (health status, echocardiographic/cardiac biomarkers) were also assessed. RESULTS: Among 282 randomized patients (mean [SD] age, 59.1 [12.9] years; 115 female [40.8%], 167 male [59.2%]), 263 (93.3%) had core laboratory-validated exercise testing at baseline and week 24. Integrated composite exercise performance improved in the aficamten group (mean [SD] z score, 0.17 [0.51]) from baseline to week 24, whereas the placebo group deteriorated (mean [SD] z score, -0.19 [0.45]), yielding a placebo-corrected improvement of 0.35 (95% CI, 0.25-0.46; P <.001). Further, aficamten treatment demonstrated significant improvements in total workload, circulatory power, exercise duration, heart rate reserve, peak heart rate, ventilatory efficiency, ventilatory power, and anaerobic threshold (all P <.001). In the aficamten group, large improvements (≥3.0 mL/kg per minute) in pVO2 were more common than large reductions (32% and 2%, respectively) compared with placebo (16% and 11%, respectively). Improvements in both components of the primary outcome, pVO2 and VE/VCO2 slope throughout exercise, were significantly correlated with improvements in symptom burden and hemodynamics (all P <.05). CONCLUSIONS AND RELEVANCE: This prespecified analysis of the SEQUOIA-HCM randomized clinical trial found that aficamten treatment improved a broad range of exercise performance measures. These findings offer valuable insight into the therapeutic effects of aficamten. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05186818.

• MeSH
• Double-Blind Method MeSH
• Cardiomyopathy, Hypertrophic * physiopathology   drug therapy   MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged MeSH
• Oxygen Consumption physiology   MeSH
• Cardiac Myosins MeSH
• Exercise Tolerance * physiology   MeSH
• Exercise Test * methods   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase III MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH

Heart failure (HF) is a clinical syndrome characterized by the inability of the heart to provide adequate perfusion to tissues and organs, resulting in typical symptoms such as fatigue, dyspnea, dyspepsia, or swelling due to decreased cardiac output. With its increasing prevalence, heart failure has become one of the leading causes of morbidity and mortality worldwide, imposing a significant burden on the population by reducing long-term life expectancy and raising hospital costs. Indeed, over 20 million people worldwide suffer from heart failure, with a 5-year mortality rate of 60-70%. As heart failure progresses, various structural and metabolic changes occur within the myocardium and organ systems. In the past two decades, therapeutic options for heart failure patients have significantly expanded. In addition to novel pharmacological treatment, advanced surgical methods such as heart transplantation (HTx) and the implantation of durable left ventricular assist devices (LVADs) are available for patients with end-stage heart failure. This review discusses the pathophysiological aspects and metabolic consequences of heart failure and metabolic changes, as well as the benefits and challenges of implanting a left ventricular assist device. Furthermore, future targets for heart failure diagnostics and therapy will be highlighted.

• Publication type
• Journal Article MeSH
• Review MeSH