Pulmonary hypertension (PH) associated with left heart failure (LHF) (PH-LHF) is one of the most common causes of PH. It directly contributes to symptoms and reduced functional capacity and negatively affects right heart function, ultimately leading to a poor prognosis. There are no specific treatments for PH-LHF, despite the high number of drugs tested so far. This scientific document addresses the main knowledge gaps in PH-LHF with emphasis on pathophysiology and clinical trials. Key identified issues include better understanding of the role of pulmonary venous versus arteriolar remodelling, multidimensional phenotyping to recognize patient subgroups positioned to respond to different therapies, and conduct of rigorous pre-clinical studies combining small and large animal models. Advancements in these areas are expected to better inform the design of clinical trials and extend treatment options beyond those effective in pulmonary arterial hypertension. Enrichment strategies, endpoint assessments, and thorough haemodynamic studies, both at rest and during exercise, are proposed to play primary roles to optimize early-stage development of candidate therapies for PH-LHF.

• Klíčová slova
• Drug, Heart failure, Pulmonary hypertension, Therapy, Translational,
• MeSH
• funkce pravé komory srdeční * fyziologie   MeSH
• lidé MeSH
• plicní hypertenze * patofyziologie   etiologie   terapie   MeSH
• plicní oběh * fyziologie   MeSH
• srdeční selhání * patofyziologie   komplikace   terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Lung function tests (i.e., spirometry, flow volume, and body plethysmography) were performed in 213 patients (age 6-21 years, mean 11.3 years) with hemodynamically significant congenital heart defects: atrial septal defect, ventricular septal defect (VSD), tetralogy of Fallot, aortic stenosis and coarctation of the aorta. We measured lung vital capacity, total lung capacity (TLC), residual volume (RV), the percentage ratio of the latter two measurements (%RV/TLC), maximal expiratory flow rates at 25% and 50% of vital capacity, and specific airway conductance. Pulmonary restriction dominated in patients with tetralogy of Fallot; pulmonary hyperinflation was more frequent in patients with VSD and coarctation of the aorta; and obstruction of the airways was observed most frequently in patients with tetralogy of Fallot. In conclusion, we found a range of pathologic lung function parameters in patients with hemodynamically significant congenital heart defects.

• MeSH
• dítě MeSH
• dospělí MeSH
• hemodynamika MeSH
• lidé MeSH
• mladiství MeSH
• plíce patofyziologie   MeSH
• respirační funkční testy MeSH
• vrozené srdeční vady patofyziologie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• Publikační typ
• časopisecké články MeSH

Static lung volumes, lung elasticity, and airway patency indices were measured in 47 children operated on for ventricular septal defect (VSD). Open-heart surgery was performed at the age of 0.6-12.0 years (median 4.1 years). In the first group (34 subjects), after primary repair of the VSD, there was an increase in lung recoil pressure at 100% of total lung capacity (TLC) (128% of the predicted value) and a reduction in specific airway conductance (sGaw) (75% of the predicted value). In the second group (13 patients), who had had previous pulmonary artery banding at 0.2-4.0 years (median 0.7 year) there was an increased functional residual capacity/TLC ratio (111% of predicted value), reduced sGaw (69% of predicted value), and reduced maximum expiratory flow at 25% of vital capacity (79% of predicted value). Lung volumes were insignificantly reduced in both groups. The frequency of lung function disturbances was similar in the two groups (71% of patients in the former group and 77% of patients in the latter group). A linear positive correlation between specific airway conductance and the mean pulmonary artery pressure (mPAP) (r = 0.793, p < 0.006) was observed in children with an mPAP <30 mmHg prior to open-heart surgery. A positive correlation between static recoil pressure at full inflation and mPAP (r = 0.545, p < 0.03) was found in children with an mPAP > 30 mmHg. The severity of congenital heart disease prior to surgery and the influence of the timing of the surgical procedures may cause the differences in lung function tests between the groups.

• MeSH
• arteria pulmonalis chirurgie   MeSH
• celková kapacita plic MeSH
• defekty komorového septa chirurgie   MeSH
• dítě MeSH
• hemodynamika MeSH
• kardiochirurgické výkony škodlivé účinky   metody   MeSH
• kojenec MeSH
• lidé MeSH
• mechanika dýchání * MeSH
• obstrukce dýchacích cest etiologie   MeSH
• poddajnost plic MeSH
• předškolní dítě MeSH
• respirační funkční testy MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Left atrial (LA) structure and function are altered in most heart failure (HF) patients, but there may be fundamental differences in LA properties between HF with preserved (HFpEF) and reduced ejection fraction (HFrEF). METHODS AND RESULTS: One hundred ninety-eight HF patients (51% HFpEF, New York Heart Association 3.1±0.7) and 40 HF-free controls underwent catheterization, echocardiography, and follow-up. Compared with controls, HF patients had larger and more dysfunctional left atria. At identical mean LA pressure (20 versus 20 mm Hg; P=0.9), HFrEF patients had larger LA volumes (LA volume index 50 versus 41 mL/m(2); P<0.001), whereas HFpEF patients had higher LA peak pressures, lower LA minimal pressures, higher LA stiffness (0.79 versus 0.48 mm Hg/mL; P<0.001), greater LA pulsatility (19 versus 13 mm Hg; P<0.001), and higher wall stress variations. Despite smaller LA volumes, better function, and less mitral regurgitation, HFpEF patients had more atrial fibrillation (42 versus 26%; P=0.02). LA dysfunction was associated with increased pulmonary vascular resistance and right ventricular dysfunction in both HF phenotypes. After a median follow-up of 350 days, 31 HFpEF and 28 HFrEF patients died. LA function (total LA EF) was associated with lower mortality in HFpEF (hazard ratio 0.43; 95% confidence interval, 0.2-0.9; P<0.05), but not in HFrEF. CONCLUSIONS: HFrEF is characterized by greater eccentric LA remodeling, whereas HFpEF by increased LA stiffness, which might contribute to greater atrial fibrillation burden. LA function is associated with pulmonary vascular disease and right HF in both HF phenotypes, but is associated with outcome more closely in HFpEF, supporting efforts to improve LA function in this cohort.

• Klíčová slova
• atrial fibrillation, heart failure, left atrial function, pulmonary hypertension, right ventricle,
• MeSH
• cévní rezistence fyziologie   MeSH
• dysfunkce pravé srdeční komory patofyziologie   MeSH
• fenotyp MeSH
• lidé středního věku MeSH
• lidé MeSH
• prognóza MeSH
• remodelace síní fyziologie   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• srdce - funkce levé síně fyziologie   MeSH
• srdeční selhání patofyziologie   MeSH
• tepový objem fyziologie   MeSH
• tuhost cévní stěny fyziologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH

1. Definition. The isolated perfused heart according to Langendorff is a preparation which is easily obtained from all warm-blooded animals. The heart is usually perfused at constant pressure, but frequently at constant flow, mostly with oxygenated saline solutions. The ventricles do not fill with the perfusate and therefore do not perform pressure-volume work. If, however, an intraventricular balloon is inserted, the ventricle can contract isovolumetrically. 2. Measuring parameters. Mechanical parameters of the working myocardium (contractile force, volume, ventricular diameter), mean coronary flow, bioelectrical parameters (EKG, monophasic injury potentials), and cardiac rhythm can be measured and recorded. 3. Function tests. The intact function of the working myocardium and the coronary vessels should be examined using various simple tests regarding the myocardium, the smooth musculature, and the endothelium of coronary vessels. 4. Possible applications. In the Langendorff-heart of normal or pretreated animals, inotropic, chronotropic, antiarrhythmic or vasoactive substances can be investigated in the steady state or by means of specific stress tests. In addition, the preparation is particularly suitable for biochemical studies of myocardial metabolism. 6. Advantages. Due to the technical ease with which a variety of parameters can be measured, a single heart can provide maximum information about the condition of the myocardium and the coronary vessels. Thus, it is not surprising to find that 90 years after its first description, the isolated perfused heart according to Langendorff continues to be utilized.

• MeSH
• elektrofyziologie MeSH
• funkční vyšetření srdce MeSH
• kontrakce myokardu MeSH
• koronární cirkulace MeSH
• perfuze metody   MeSH
• savci MeSH
• srdce fyziologie   MeSH
• srdeční frekvence MeSH
• techniky in vitro MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Pulmonary congestion due to heart failure causes abnormal lung function. Cardiac resynchronization therapy (CRT) is a proven effective treatment for heart failure. The aim of this study was to test the hypothesis that CRT promotes increased lung volumes, bronchial conductance, and gas diffusion. Forty-four consecutive patients with heart failure were prospectively investigated before and after CRT. Spirometry, gas diffusion (diffusing capacity for carbon monoxide), cardiopulmonary exercise testing, New York Heart Association class, brain natriuretic peptide, the left ventricular ejection fraction, left atrial volume, and right ventricular systolic pressure were assessed before and 4 to 6 months after CRT. Pre- and post-CRT measures were compared using either paired Student's t tests or Wilcoxon's matched-pair test; p values <0.05 were considered significant. Improved New York Heart Association class, left ventricular ejection fraction, left atrial volume, right ventricular systolic pressure, and brain natriuretic peptide were observed after CRT (p <0.05 for all). Spirometry after CRT demonstrated increased percentage predicted total lung capacity (90 ± 17% vs 96 ± 15%, p <0.01) and percentage predicted forced vital capacity (80 ± 19% vs 90 ± 19%, p <0.01). Increased percentage predicted total lung capacity was significantly correlated with increased peak exercise end-tidal carbon dioxide (r = 0.43, p = 0.05). Increased percentage predicted forced vital capacity was significantly correlated with decreased right ventricular systolic pressure (r = -0.30, p = 0.05), body mass index (r = -0.35, p = 0.02) and creatinine (r = -0.49, p = 0.02), consistent with an association of improved bronchial conductance and decreased congestion. Diffusing capacity for carbon monoxide did not significantly change. In conclusion, increased lung volumes and bronchial conductance due to decreased pulmonary congestion and increased intrathoracic space contribute to an improved breathing pattern and decreased hyperventilation after CRT. Persistent alveolar-capillary membrane remodeling may account for unchanged diffusing capacity for carbon monoxide.

• MeSH
• fyziologie dýchací soustavy * MeSH
• lidé MeSH
• následné studie MeSH
• plíce patofyziologie   MeSH
• prognóza MeSH
• respirační funkční testy MeSH
• respirační insuficience etiologie   patofyziologie   MeSH
• senioři MeSH
• srdeční resynchronizační terapie metody   MeSH
• srdeční selhání komplikace   patofyziologie   terapie   MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• srovnávací studie MeSH

AIM: Vericiguat significantly reduced the primary composite outcome of heart failure (HF) hospitalization or cardiovascular death in the VICTORIA trial. It is unknown if these outcome benefits are related to reverse left ventricular (LV) remodelling with vericiguat in patients with HF with reduced ejection fraction (HFrEF). The aim of this study was to compare the effects of vericiguat versus placebo on LV structure and function after 8 months of therapy in patients with HFrEF. METHODS AND RESULTS: Standardized transthoracic echocardiography (TTE) was performed at baseline and after 8 months of therapy in a subset of HFrEF patients in VICTORIA. The co-primary endpoints were changes in LV end-systolic volume index (LVESVI) and LV ejection fraction (LVEF). Quality assurance and central reading were performed by an echocardiographic core laboratory blinded to treatment assignment. A total of 419 patients (208 vericiguat, 211 placebo) with high-quality paired TTE at baseline and 8 months were included. Baseline clinical characteristics were well balanced between treatment groups and echocardiographic characteristics were representative of patients with HFrEF. LVESVI significantly declined (60.7 ± 26.8 to 56.8 ± 30.4 ml/m2 ; p < 0.01) and LVEF significantly increased (33.0 ± 9.4% to 36.1 ± 10.2%; p < 0.01) in the vericiguat group, but similarly in the placebo group (absolute changes for vericiguat vs. placebo: LVESVI -3.8 ± 15.4 vs. -7.1 ± 20.5 ml/m2 ; p = 0.07 and LVEF +3.2 ± 8.0% vs. +2.4 ± 7.6%; p = 0.31). The absolute rate per 100 patient-years of the primary composite endpoint at 8 months tended to be lower in the vericiguat group (19.8) than the placebo group (29.6) (p = 0.07). CONCLUSIONS: In this pre-specified echocardiographic study, significant improvements in LV structure and function occurred over 8 months in both vericiguat and placebo in a high-risk HFrEF population with recent worsening HF. Further studies are warranted to define the mechanisms of vericiguat's benefit in HFrEF.

• Klíčová slova
• Echocardiography, Heart failure with reduced ejection fraction, Left ventricular function, Left ventricular structure, Vericiguat,
• MeSH
• echokardiografie MeSH
• funkce levé komory srdeční MeSH
• heterocyklické sloučeniny bicyklické * MeSH
• lidé MeSH
• srdeční selhání * diagnostické zobrazování   farmakoterapie   chemicky indukované   MeSH
• tepový objem MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• heterocyklické sloučeniny bicyklické * MeSH
• vericiguat MeSH Prohlížeč

A high-fructose intake (HFI) in food, sweetened beverages, and soft drinks appears to be one of the risk factors that worsens human metabolic and cardiovascular health, although the more accurate mechanism remains unclear. Hypertriglyceridemic (HTG) rats represent a suitable animal model of metabolic syndrome where the consumption of an HFI could have an additional aggravating impact. We aimed to study the effect of fructose on the heart functions. Male HTG rats had HFI or a standard diet for five weeks. Heart function was tested ex vivo on the perfused heart using the Langendorff technique. Isolated hearts underwent 25 min ischemia (I) and 30 min reperfusion (R). Left ventricular developed pressure (LVDP), ventricular premature beats, and dysrhythmias were monitored during R. At the end of the R, ventricular fibrillation (VF) was evoked electrically. Systolic blood pressure, glucose level, serum total cholesterol (TC), triglycerides (TAG), and thiobarbituric acid reactive substances (TBARS) in the kidney were determined. The LVDP showed a reduced return to the input values, the duration of VF in R increased, and the threshold for VF induction decreased. Serum TC, TAG, and kidney TBARS were increased. The effect of HFI on heart ventricular impairment was associated with the reduced threshold for induction of VF and aggravated dyslipidemia. The results point to the adverse impact of dietary high-fructose intake in rats with hypertriglyceridemia.

• Klíčová slova
• aortic endothelium-dependent relaxation, heart function, high-fructose intake, hypertriglyceridemic rats, lipid profile,
• MeSH
• fruktosa * škodlivé účinky   MeSH
• hypertriglyceridemie * patofyziologie   komplikace   MeSH
• krysa rodu Rattus MeSH
• modely nemocí na zvířatech MeSH
• potkani Wistar MeSH
• srdce * účinky léků   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fruktosa * MeSH

BACKGROUND: The mechanisms and relevance of impaired glucose homeostasis in advanced heart failure (HF) are poorly understood. The study goals were to examine glucose regulation, pancreatic endocrine function, and metabolic factors related to prognosis in patients with nondiabetic advanced HF. METHODS AND RESULTS: In total, 140 advanced HF patients without known diabetes mellitus and 21 sex-, age-, and body mass index-matched controls underwent body composition assessment, oral glucose tolerance testing, and measurement of glucose-regulating hormones to model pancreatic β-cell secretory response. Compared with controls, HF patients had similar fasting glucose and insulin levels but higher levels after oral glucose tolerance testing. Insulin secretion was not impaired, but with increasing HF severity, there was a reduction in glucose, insulin, and insulin/glucagon ratio-a signature of starvation. The insulin/C-peptide ratio was decreased in HF, indicating enhanced insulin clearance, and this was correlated with lower cardiac output, hepatic insufficiency, right ventricular dysfunction, and body wasting. After a median of 449 days, 41% of patients experienced an adverse event (death, urgent transplant, or assist device). Increased glucagon and, paradoxically, low fasting plasma glucose displayed the strongest relations to outcome (P=0.01). Patients in the lowest quartile of fasting plasma glucose (3.8-5.1 mmol·L-1, 68-101 mg·dL-1) had 3-times higher event risk than in the top quartile (6.0-7.9 mmol·L-1, 108-142 mg·dL-1; relative risk: 3.05 [95% confidence interval, 1.46-6.77]; P=0.002). CONCLUSIONS: Low fasting plasma glucose and increased glucagon are robust metabolic predictors of adverse events in advanced HF. Pancreatic insulin secretion is preserved in advanced HF, but levels decrease with increasing HF severity due to enhanced insulin clearance that is coupled with right heart failure and cardiac cachexia.

• Klíčová slova
• cachexia, glucagon/glucagon‐like peptide, glucose, heart failure, insulin, metabolism, obesity paradox, right ventricular dysfunction, starvation,
• MeSH
• biologické markery krev   MeSH
• časové faktory MeSH
• dysfunkce pravé srdeční komory krev   diagnóza   patofyziologie   MeSH
• funkce pravé komory srdeční MeSH
• glukagon krev   MeSH
• glukózový toleranční test MeSH
• homeostáza MeSH
• inzulin krev   MeSH
• kachexie krev   diagnóza   patofyziologie   MeSH
• Kaplanův-Meierův odhad MeSH
• krevní glukóza metabolismus   MeSH
• Langerhansovy ostrůvky metabolismus   patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prognóza MeSH
• rizikové faktory MeSH
• senioři MeSH
• srdeční selhání krev   diagnóza   patofyziologie   MeSH
• studie případů a kontrol MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• glukagon MeSH
• inzulin MeSH
• krevní glukóza MeSH

AIMS: Liver pathology caused by cardiac dysfunction is relatively well recognized, however, its clinical importance has not been fully evaluated. The aim of this study was to assess the prevalence of liver function tests (LFTs) abnormalities and to identify associated factors mediating hepatic impairment in patients with acute heart failure (AHF). METHODS: The AHEAD (Acute Heart Failure Database) registry is a database conducted in 9 university hospitals and 5 regional health care facilities in the Czech Republic. From December 2004 to October 2012, the data of 8818 patients were included. The inclusion criteria for the database followed the European guidelines for AHF. Serum activities of all LFTs and total bilirubin were available in 1473 patients at the baseline. RESULTS: In patients with AHF, abnormal LFTs were seen in 76% patients (total bilirubin in 34%, γ-glutamyltransferase in 44%, alkaline phosphatase in 20%, aspartate aminotransferase in 42%, alanine aminotransferase in 35%). Patients with cardiogenic shock were more likely to have LFTs abnormalities compared to mild AHF and pulmonary oedema. LFTs abnormalities were strongly associated with AHF severity (left ventricular ejection fraction and NYHA functional class) and clinical manifestation. While hepatocellular LFTs pattern predominated in left sided forward AHF, cholestatic profile occurred mainly in bilateral and right sided AHF. Additionally, patients with moderate to severe tricuspid regurgitation had significantly higher prevalence of abnormalities in cholestatic LFTs. CONCLUSIONS: Defining the LFTs profile typical for AHF plays an important role in management of AHF patients, since it may avoid redundant hepatic investigations and diagnostic misinterpretations.

• Klíčová slova
• bilirubin, congestive hepatopathy, heart failure, ischemic hepatitis, liver function tests,
• MeSH
• akutní nemoc MeSH
• alkalická fosfatasa krev   MeSH
• aspartátaminotransferasy krev   MeSH
• gama-glutamyltransferasa krev   MeSH
• jaterní testy MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoci jater epidemiologie   etiologie   metabolismus   MeSH
• prevalence MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• srdeční selhání komplikace   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• alkalická fosfatasa MeSH
• aspartátaminotransferasy MeSH
• gama-glutamyltransferasa MeSH