Blood pressure control in hypertensive sleep apnoea patients of the European Sleep Apnea Database cohort - effects of positive airway pressure and antihypertensive medication.

Aims: We analysed longitudinal blood pressure (BP) data from hypertensive obstructive sleep apnoea (OSA) patients in the European Sleep Apnea Database cohort. The study investigated the interaction between positive airway pressure (PAP)-induced BP change and antihypertensive treatment (AHT). Methods and results: Hypertensive patients with AHT [monotherapy/dual therapy n = 1283/652, mean age 59.6 ± 10.7/60.6 ± 10.3 years, body mass index (BMI) 34.2 ± 6.5/34.8 ± 7.0 kg/m2, apnoea-hypopnoea index 46 ± 25/46 ± 24 n/h, proportion female 29/26%, respectively] started PAP treatment. Office BP at baseline and 2- to 36-month follow-up were assessed. The interaction between AHT drug classes and PAP on BP was quantified and the influences of age, gender, BMI, co-morbidities, BP at baseline, and study site were evaluated. Following PAP treatment (daily usage, 5.6 ± 1.6/5.7 ± 1.9 h/day), systolic BP was reduced by -3.9 ± 15.5/-2.8 ± 17.7 mmHg in mono/dual AHT and diastolic BP by -3.0 ± 9.8/-2.7 ± 10.8 mmHg, respectively, all P < 0.0001. Systolic and diastolic BP control was improved following PAP treatment (38/35% to 54/46% and 67/67% to 79/74%, mono/dual AHT, respectively). PAP treatment duration predicted a larger BP improvement in the monotherapy group. Intake of renin-angiotensin blockers [angiotensin converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB)] alone or in any AHT combination was associated with better BP control. The AHT-dependent BP improvement was independent of confounders. Conclusion: In this pan-European OSA patient cohort, BP control improved following initiation of PAP. Longer PAP treatment duration, was associated with a favourable effect on BP. Our study suggests that ACEI/ARB, alone or in combination with other drug classes, provides a particularly strong reduction of BP and better BP control when combined with PAP in OSA.

Obstructive Sleep Apnea and a Comprehensive Remotely Supervised Rehabilitation Program: Protocol for a Randomized Controlled Trial.

BACKGROUND: Obstructive sleep apnea (OSA) is characterized by recurrent, intermittent partial or complete obstruction of the upper respiratory tract during sleep, which negatively affects the patient's daily quality of life (QoL). Middle-aged and older men who smoke and have obesity are most at risk. Even though the use of continuous positive airway pressure (CPAP) during sleep remains the gold standard treatment, various rehabilitation methods, such as exercise, respiratory therapy, myofunctional therapy, and nutritional lifestyle interventions, also appear to be effective. Moreover, it is increasingly recommended to use alternative or additional therapy options in combination with CPAP therapy. OBJECTIVE: This study aims to evaluate if a comprehensive home-based, remotely supervised rehabilitation program (tele-RHB), in combination with standard therapy, can improve OSA severity by decreasing the apnea-hypopnea index (AHI); improve objective parameters of polysomnographic, spirometric, anthropometric, and body composition examinations; improve lipid profile, maximal mouth pressure, and functional capacity tests; and enhance the subjective perception of QoL, as well as daytime sleepiness in male participants with moderate to severe OSA. Our hypothesis is that a combination of the tele-RHB program and CPAP therapy will be more effective by improving OSA severity and the abovementioned parameters. METHODS: This randomized controlled trial aims to recruit 50 male participants between the ages of 30 and 60 years with newly diagnosed moderate to severe OSA. Participants will be randomized 1:1, either to a 12-week tele-RHB program along with CPAP therapy or to CPAP therapy alone. After the completion of the intervention, the participants will be invited to complete a 1-year follow-up. The primary outcomes will be the polysomnographic value of AHI, Epworth Sleepiness Scale score, 36-Item Short Form Health Survey (SF-36) score, percentage of body fat, 6-minute walk test distance covered, as well as maximal inspiratory and expiratory mouth pressure values. Secondary outcomes will include polysomnographic values of oxygen desaturation index, supine AHI, total sleep time, average heart rate, mean oxygen saturation, and the percentage of time with oxygen saturation below 90%; anthropometric measurements of neck, waist, and hip circumference; BMI values; forced vital capacity; forced expiratory volume in 1 second; World Health Organization's tool to measure QoL (WHOQOL-BREF) score; and lipid profile values. RESULTS: Study recruitment began on October 25, 2021, and the estimated study completion date is December 2024. Analyses will be performed to examine whether the combination of the tele-RHB program and CPAP therapy will be more effective in the reduction of OSA severity and improvement of QoL, body composition and circumferences, exercise tolerance, lipid profile, as well as respiratory muscle and lung function, compared to CPAP therapy alone. CONCLUSIONS: The study will evaluate the effect of a comprehensive tele-RHB program on selected parameters mentioned above in male participants. The results of this intervention could help the further development of novel additional therapeutic home-based options for OSA. TRIAL REGISTRATION: ClinicalTrials.gov NCT04759456; https://clinicaltrials.gov/ct2/show/NCT04759456. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/47460.

Comprehensive home-based telerehabilitation in a morbidly obese male patient with severe obstructive sleep apnea. A case report.

BACKGROUND: Rehabilitation may be an effective additional treatment method in patients with obstructive sleep apnea (OSA). Physical exercise, weight reduction, pulmonary rehabilitation, and myofunctional therapy (MT) represent beneficial components of rehabilitation recommended as a possible adjunct to standard OSA treatment. METHODS AND RESULTS: A 54-year-old man with morbid obesity, long-lasting snoring, breathing pauses, frequent waking, as well as persistent drowsiness and fatigue during the day underwent polysomnography (PSG) to investigate suspected OSA. Severe OSA was confirmed by PSG and a 12-week comprehensive, home-based telerehabilitation program (tele-RHB program) along with continuous positive airway pressure (CPAP) therapy was implemented. The tele-RHB program included regular teleconsultations, aerobic-endurance training, MT, inspiratory and expiratory muscle training, as well as recommendations on proper nutrition, a healthy lifestyle, and behavioral changes. Following the treatment, the patient's quality of life (QoL), exercise capacity, lung function, and OSA severity significantly improved. The patient achieved an overall 19.9 kg reduction in weight, of which 16.2 kg was body fat, and his apnea-hypopnea index decreased by 42.6 episodes/hour. CONCLUSION: Our case report suggests that the comprehensive home-based tele-RHB program adjunct to CPAP therapy may be a novel approach for improving OSA severity, a patient's QoL, exercise capacity, lung function and body composition. It is important to note that such a program should be optional, however it may be needed to achieve the highest possible overall improvement in a patient's life. Further clinical investigations are needed to determine the therapeutic efficacy and clinical potential of this tele-RHB program.

Clinical characteristics and positive airway pressure adherence among elderly European sleep apnoea patients from the ESADA cohort.

Background: The prevalence of obstructive sleep apnoea (OSA) is growing as the population is ageing. However, data on the clinical characteristics of elderly patients with OSA and their adherence to positive airway pressure (PAP) treatment are scarce. Methods: Data from 23 418 30-79-year-old OSA patients prospectively collected into the ESADA database during 2007-2019 were analysed. Information on PAP use (h·day-1) in association with a first follow-up visit was available for 6547 patients. The data was analysed according to 10-year age groups. Results: The oldest age group was less obese, less sleepy and had a lower apnoea-hypopnoea index (AHI) compared with middle-aged patients. The insomnia phenotype of OSA was more prevalent in the oldest age group than in the middle-aged group (36%, 95% CI 34-38 versus 26%, 95% CI 24-27, p<0.001). The 70-79-year-old group adhered to PAP therapy equally well as the younger age groups with a mean PAP use of 5.59 h·day-1 (95% CI 5.44-5.75). PAP adherence did not differ between clinical phenotypes based on subjective daytime sleepiness and sleep complaints suggestive of insomnia in the oldest age group. A higher score on the Clinical Global Impression Severity (CGI-S) scale predicted poorer PAP adherence. Conclusion: The elderly patient group was less obese, less sleepy, had more insomnia symptoms and less severe OSA, but were rated to be more ill compared with the middle-aged patients. Elderly patients with OSA adhered to PAP therapy equally well as middle-aged patients. Low global functioning (measured by CGI-S) in the elderly patient predicted poorer PAP adherence.

Hypertension treatment in patients with sleep apnea from the European Sleep Apnea Database (ESADA) cohort - towards precision medicine.

We recruited 5,970 hypertensive patients with obstructive sleep apnea (OSA) on current antihypertensive treatment from the European Sleep Apnea Database (ESADA) cohort. The group was subdivided into those receiving monotherapy (n = 3,594) and those receiving dual combined therapy (n = 2,376). We studied how major OSA confounders like age, gender, and body mass index as well as the degree of sleep apnea modified office systolic and diastolic blood pressure. Beta-blockers alone or in combination with a diuretic were compared with other antihypertensive drug classes. Monotherapy with beta-blocker was associated with lower systolic blood pressure, particularly in non-obese middle-aged males with hypertension. Conversely, the combination of a beta-blocker and a diuretic was associated with lower systolic and diastolic blood pressure in hypertensive patients with moderate-severe OSA. Systolic blood pressure was better controlled in female patients using this combined treatment. Our cross-sectional data suggest that specific clinical characteristics and type of antihypertensive medication influence the degree of blood pressure control in hypertensive OSA patients. Controlled trials are warranted.

Relation between Mid-Regional Pro-Adrenomedullin in Patients with Chronic Heart Failure and the Dose of Diuretics in 2-Year Follow-Up-Data from FAR NHL Registry.

Background and Objectives: The aim of this paper is to evaluate the impact of humoral substance mid-regional pro-adrenomedullin (MR-proADM) on the two-year survival of patients with chronic heart failure and relate it to the dosage of furosemide. Materials and Methods: The data is taken from the stable systolic heart failure (EF < 50%) FAR NHL registry (FARmacology and NeuroHumoraL activation). The primary endpoint at two-year follow-up was death, heart transplantation, or LVAD implantation. Results: A total of 1088 patients were enrolled in the FAR NHL registry; MR-proADM levels were available for 569 of them. The mean age was 65 years, and 81% were male. The aetiology of HF was ischemic heart disease in 53% and dilated cardiomyopathy in 41% of patients. The mean EF was 31 ± 9%. Statistically significant differences (p < 0.001) were obtained in several parameters: patients with higher MR-proADM levels were older, rated higher in NYHA class, suffered more often from lower limb oedema, and had more comorbidities such as hypertension, atrial fibrillation, diabetes, and renal impairment. MR-proADM level was related to furosemide dose. Patients taking higher doses of diuretics had higher MR-proADM levels. The mean MR-proADM level without furosemide (n = 122) was 0.62 (±0.55) nmol/L, with low dose (n = 113) 1−39 mg/day was 0.67 (±0.30) nmol/L, with mid dose (n = 202) 40−79 mg/day was 0.72 (±0.34) nmol/L, with high dose (n = 58) 80−119 mg/day was 0.85 (±0.40) nmol/L, and with maximum dose (n = 74) ≥120 mg/day was 1.07 (±0.76) nmol/L, p < 0.001. Patients with higher MR-proADM levels were more likely to achieve the primary endpoint at a two-year follow-up (p < 0.001) according to multivariant analysis. Conclusions: Elevated plasma MR-proADM levels in patients with chronic heart failure are associated with an increased risk of death and hospitalization. Higher MR-proADM levels in combination with increased use of loop diuretics reflect residual congestion and are associated with a higher risk of severe disease progression.

Management of obstructive sleep apnea in Europe - A 10-year follow-up.

OBJECTIVE: In 2010, a questionnaire-based study on obstructive sleep apnea (OSA) management in Europe identified differences regarding reimbursement, sleep specialist qualification, and titration procedures. Now, 10 years later, a follow-up study was conducted as part of the ESADA (European Sleep Apnea Database) network to explore the development of OSA management over time. METHODS: The 2010 questionnaire including questions on sleep diagnostic, reimbursement, treatment, and certification was updated with questions on telemedicine and distributed to European Sleep Centers to reflect European OSA management practice. RESULTS: 26 countries (36 sleep centers) participated, representing 20 ESADA and 6 non-ESADA countries. All 21 countries from the 2010 survey participated. In 2010, OSA diagnostic procedures were performed mainly by specialized physicians (86%), whereas now mainly by certified sleep specialists and specialized physicians (69%). Treatment and titration procedures are currently quite homogenous, with a strong trend towards more Autotitrating Positive Airway Pressure treatment (in hospital 73%, at home 62%). From 2010 to 2020, home sleep apnea testing use increased (76%-89%) and polysomnography as sole diagnostic procedure decreased (24%-12%). Availability of a sleep specialist qualification increased (52%-65%) as well as the number of certified polysomnography scorers (certified physicians: 36%-79%; certified technicians: 20%-62%). Telemedicine, not surveyed in 2010, is now in 2020 used in diagnostics (8%), treatment (50%), and follow-up (73%). CONCLUSION: In the past decade, formal qualification of sleep center personnel increased, OSA diagnostic and treatment procedures shifted towards a more automatic approach, and telemedicine became more prominent.

Prognostic value of high-sensitivity cardiac troponin I in heart failure patients with mid-range and reduced ejection fraction.

BACKGROUND: The identification of high-risk heart failure (HF) patients makes it possible to intensify their treatment. Our aim was to determine the prognostic value of a newly developed, high-sensitivity troponin I assay (Atellica®, Siemens Healthcare Diagnostics) for patients with HF with reduced ejection fraction (HFrEF; LVEF < 40%) and HF with mid-range EF (HFmrEF) (LVEF 40%-49%). METHODS AND RESULTS: A total of 520 patients with HFrEF and HFmrEF were enrolled in this study. Two-year all-cause mortality, heart transplantation, and/or left ventricular assist device implantation were defined as the primary endpoints (EP). A logistic regression analysis was used for the identification of predictors and development of multivariable models. The EP occurred in 14% of the patients, and these patients had higher NT-proBNP (1,950 vs. 518 ng/l; p < 0.001) and hs-cTnI (34 vs. 17 ng/l, p < 0.001) levels. C-statistics demonstrated that the optimal cut-off value for the hs-cTnI level was 17 ng/l (AUC 0.658, p < 0.001). Described by the AUC, the discriminatory power of the multivariable model (NYHA > II, NT-proBNP, hs-cTnI and urea) was 0.823 (p < 0.001). Including heart failure hospitalization as the component of the combined secondary endpoint leads to a diminished predictive power of increased hs-cTnI. CONCLUSION: hs-cTnI levels ≥ 17 ng/l represent an independent increased risk of an adverse prognosis for patients with HFrEF and HFmrEF. Determining a patient's hs-cTnI level adds prognostic value to NT-proBNP and clinical parameters.

Impact of temperature on obstructive sleep apnoea in three different climate zones of Europe: Data from the European Sleep Apnoea Database (ESADA).

Recent studies indicate that ambient temperature may modulate obstructive sleep apnoea (OSA) severity. However, study results are contradictory warranting more investigation in this field. We analysed 19,293 patients of the European Sleep Apnoea Database (ESADA) cohort with restriction to the three predominant climate zones according to the Köppen-Geiger climate classification: Cfb (warm temperature, fully humid, warm summer), Csa (warm temperature, summer dry, hot summer), and Dfb (snow, fully humid, warm summer). Average outside temperature values were obtained and several hierarchical regression analyses were performed to investigate the impact of temperature on the apnea-hypopnea index (AHI), oxygen desaturation index (ODI), time of oxygen saturation <90% (T90) and minimum oxygen saturation (MinSpO2 ) after controlling for confounders including age, body mass index, gender, and air conditioning (A/C) use. AHI and ODI increased with higher temperatures with a standardised coefficient beta (ß) of 0.28 for AHI and 0.25 for ODI, while MinSpO2 decreased with a ß of -0.13 (all results p < .001). When adjusting for climate zones, the temperature effect was only significant in Cfb (AHI: ß = 0.11) and Dfb (AHI: ß = 0.08) (Model 1: p < .001). The presence of A/C (3.9% and 69.3% in Cfab and Csa, respectively) demonstrated only a minor increase in the prediction of the variation (Cfb: AHI, R2 +0.003; and Csa: AHI, R2 +0.007; both p < .001). Our present study indicates a limited but consistent influence of environmental temperature on OSA severity and this effect is modulated by climate zones.

Impact of Sleep Apnea on Cardioembolic Risk in Patients With Atrial Fibrillation: Data From the ESADA Cohort.

BACKGROUND AND PURPOSE: An accurate determination of the cardioembolic risk in patients with atrial fibrillation (AF) is crucial to prevent consequences like stroke. Obstructive sleep apnea (OSA) is a known risk factor for both AF and stroke. We aim to explore a possible association between OSA and an increased cardioembolic risk in patients with AF. METHODS: We assessed data from the ESADA (European Sleep Apnea Database) cohort where patients with known AF and OSA were included. Parameters of OSA severity and related hypoxia like lowest Spo2 and 4% oxygen desaturation index were analyzed. Patients were stratified according to their cardioembolic risk estimated with the CHA2DS2-VASc score. RESULTS: From the initial cohort of 14 646 patients, a final set of 363 patients were included in the analysis. Indices of hypoxia during sleep were associated with increased CHA2DS2-VASc score (4% oxygen desaturation index 17.9 versus 29.6 versus 30.5 events/hour and the lowest Spo2 81.2 versus 77.8 versus 77.5% for low, moderate, and high cardioembolic risk, respectively, P<0.05). CONCLUSIONS: These results support the potential role of OSA-related hypoxia in the risk for cardioembolic complications such as stroke in patients with AF.

Increased heart rate with sleep disordered breathing in hypertrophic cardiomyopathy.

BACKGROUND: Current guidelines recommend medications with rate control properties for symptomatic patients with hypertrophic cardiomyopathy (HCM) based on the rationale that lowering heart rate (HR) improves their symptoms. Whether sleep disordered breathing (SDB) is associated with increased HR in HCM patients is not known. METHOD: We diagnosed uncontrolled SDB (oxygen desaturation index ≥5) in consecutive echocardiographically confirmed HCM patients seen at Mayo Clinic, Rochester, and analyzed their HR as recorded by a 24-h Holter monitor. We compared mean, minimum, maximum HR between those with vs without SDB. In a pilot subanalysis of HCM patients with SDB who also underwent subsequent diagnostic polysomnography (PSG), we analyzed RR interval changes coinciding with obstructive sleep apnea and hypopnea episodes. RESULTS: Of the 230 HCM patients included in this study (age 54 ± 16 years; 138 male; LVOT pressure gradient at rest 45 ± 39 mmHg), 115 (50%) patients had SDB. HCM patients with SDB were recorded to have higher mean HR (71 vs. 67 bpm; p = .002, adjusted p = .001), and this difference was most pronounced during night hours of 10 PM to 5 AM (61 vs. 67 bpm; p < .001). In the pilot analysis of the available PSG data, the release of obstructive sleep apneas and hypopneas coincided with fluctuation of HR. CONCLUSIONS: SDB is independently associated with higher mean HR in patients with HCM, and this difference is most significant during sleep. Treatment of SDB, which is readily available, should be tested as a complementary modality to the currently recommended pharmacotherapy aimed at lowering HR in patients with symptomatic HCM.

Effect of home-based high-intensity interval training using telerehabilitation among coronary heart disease patients.

INTRODUCTION: Cardiovascular diseases are the world's most common causes of morbidity and mortality in the population, including Central Europe. Cardiac rehabilitation (CR) is an effective preventive approach that includes several core components. Physical training is identified as an integral and essential part of CR. Training can positively influence several cardiovascular risk factors in people diagnosed with coronary heart disease and prevent them from clinical events. Our study aims to research the method of high-intensity interval training (HIIT) in a home environment using telerehabilitation. We assume that the HIIT form of telerehabilitation, using a heart rate monitor as a tool for backing up training data, can improve cardiorespiratory fitness and lead to higher peak oxygen uptake than the traditional moderate-intensity continuous training (MICT). METHODS: This study is designed as a monocentral randomized controlled trial at University Hospital Brno in the Czech Republic. After the coronary heart event, the suitable patients will be randomized (1:1 ratio) and separated into 2 groups: the experimental HIIT group and the control MICT group. Both groups undergo a 12-week telerehabilitation with a 1-year follow-up period. Study participants will be telemonitored during physical training in their home environment via a heart rate monitor and a web platform. Once a week, the patients will give their feedback and motivation by a telephone call.The primary outcome observed will be the effect of intervention expressed by changes in cardiorespiratory fitness. Secondary outcomes will be the health-related quality of life, anxiety, training adherence, body composition, safety, and satisfaction. DISCUSSION: The HIIT is widely researched predominantly in a center-based supervised form. Our study differs from others by the use of telemedicine and smart technologies in home-based settings. Previous home-based cardiac telerehabilitation studies have focused primarily on MICT, which has demonstrated feasibility, and results have shown similar improvements as center-based CR. There is a presumption that HIIT may be superior to MICT. However, it can be complicated to self-dose the method in the home environment. Investigators expect that HIIT research will provide insight into the possibilities of telemedicine feasibility, effect, and limitations of coronary heart disease patients' use at low to moderate cardiovascular risk.

Novel versus Traditional Inspiratory Muscle Training Regimens as Home-Based, Stand-Alone Therapies in COPD: Protocol for a Randomized Controlled Trial.

Background: Subjects with COPD frequently develop considerable weakness and deconditioning of the inspiratory musculature, which can be corrected with inspiratory muscle training (IMT). While rehabilitation centers may be able to provide IMT as part of the rather complex management of COPD, there is currently a lack of rehabilitation services in the Czech Republic. Remote IMT may then benefit subjects with COPD who are unable to attend or do not have access to rehabilitation programs. We aim at evaluating the utility of the test of incremental respiratory endurance (TIRE) as an at-home IMT method in subjects with COPD, while comparing the effectiveness of this novel training approach to the outcomes of traditional, threshold loading IMT protocols. Methods/Design: This prospective, randomized controlled trial will comprise 8 weeks of at-home IMT sessions with remote supervision followed by 4 months of unsupervised, independent IMT. Eligible subjects will be randomly assigned to one of the following three distinct home-based IMT protocols: (1) TIRE, (2) Threshold loading, and (3) Sham training. Subjects allocated to the TIRE group will train once daily using an advanced IMT electronic system (PrO2), while the other two groups will receive threshold devices. Study outcomes will include measures of inspiratory muscle strength and endurance, pulmonary function, COPD-specific symptomatology, functional exercise capacity, surrogate markers of mortality risk, mental health status and health-related quality of life. Discussion: While we acknowledge the value of threshold loading IMT protocols, we believe that the TIRE training method has the potential to provide additional clinical benefits in COPD given its sophisticated remote tracking system and ability to modulate all aspects of muscular performance, including not only strength but also endurance, power and work capacity, allowing users to achieve considerably higher inspiratory pressures throughout the full range of inspiration when compared to other more traditionally used IMT methods.

Sleep apnea and cardiovascular disease.

Sleep is a condition of physiological relaxation for the cardiovascular system, and sleep-disordered breathing disturbs it. Recurrent episodes of sleep apnea disrupt the physiological interactions between sleep and the cardiovascular system. Sleep apnea can affect not only patients quality of life with cardiovascular diseases, but also their morbidity and mortality. Thus sleep apnea becomes a significant, influential risk factor in cardiology.

Prognostic value of NT-proBNP added to clinical parameters to predict two-year prognosis of chronic heart failure patients with mid-range and reduced ejection fraction - A report from FAR NHL prospective registry.

BACKGROUND: According to guidelines, the prognosis of patients with chronic heart failure can be predicted by determining the levels of natriuretic peptides, the NYHA classification and comorbidities. The aim our work was to develop a prognostic score in chronic heart failure patients that would take account of patients' comorbidities, NYHA and NT-proBNP levels. METHODS AND RESULTS: A total of 1,088 patients with chronic heart failure with reduced ejection fraction (HFrEF) (LVEF<40%) and mid-range EF (HFmrEF) (LVEF 40-49%) were enrolled consecutively. Two-year all-cause mortality, heart transplantation and/or LVAD implantation were defined as the primary endpoint (EP). The occurrence of EP was 14.9% and grew with higher NYHA, namely 4.9% (NYHA I), 11.4% (NYHA II) and 27.8% (NYHA III-IV) (p<0.001). The occurrence of EP was 3%, 10% and 15-37% in patients with NT-proBNP levels ≤125 ng/L, 126-1000 ng/L and >1000 ng/L respectively. Discrimination abilities of NYHA and NT-proBNP were AUC 0.670 (p<0.001) and AUC 0.722 (p<0.001) respectively. The predictive value of the developed clinical model, which took account of older age, advanced heart failure (NYHA III+IV), anaemia, hyponatraemia, hyperuricaemia and being on a higher dose of furosemide (>40 mg daily) (AUC 0.773; p<0.001) was increased by adding the NT-proBNP level (AUC 0.790). CONCLUSION: The use of prediction models in patients with chronic heart failure, namely those taking account of natriuretic peptides, should become a standard in routine clinical practice. It might contribute to a better identification of a high-risk group of patients in which more intense treatment needs to be considered, such as heart transplantation or LVAD implantation.

Prescription and dosage of RAAS inhibitors in patients with chronic heart failure in the FAR NHL registry.

BACKGROUND: Congestive heart failure with reduced ejection fraction is a common clinical condition with a serious prognosis. Treatment focuses on improving the symptoms and preventing the progression of the disease. First-line therapy include angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs). METHODS: These data come from the FAR NHL registry (FARmacology and NeuroHumoraL activation). This is a multicenter database of patients with stable systolic heart failure (EF < 50 %) collected between November 2014 and November 2015. RESULTS: A population of 1 100 patients was evaluated, the mean age was 65 years, 80.8 % were male. The etiology of heart failure was ischemic heart disease (49.7 %), dilated cardiomyopathy (41.7 %) and other (8.6 %). The total prescription of ACEI/ARB was 88.4 %, the most commonly prescribed ACEI were ramipril and perindopril, ARB was losartan. The prescription of ACEI/ARBs decreased with the severity of the disease according to NYHA classification (all 88.4 %, NYHA I 95.2 %, NYHA II 89.0 %, NYHA III-IV 83.5 %, p < 0.001). 129 subjects (11.6 %) were not treated by ACEI/ARBs at all. The target dose of ACEI/ARB, as it is recommended in the ESC Guidelines, was admissioned to only 13.5 % of patients. The dose was decreasing with the severity of disease evaluated by NYHA, NT-proBNP value, systolic blood pressure and renal functions. CONCLUSIONS: These data show the tendency of pharmacological prescription of RAAS blockers (including doses), which reflects not only the severity of heart failure but also renal functions and blood pressure and points to possible reserves in up-titration of the target dose. Key words: angiotensin-converting enzyme inhibitors - angiotensin receptor blockers - FAR NHL - heart failure - pharmacotherapy - registry - target dose.

Renal Functions and Prognosis Stratification in Chronic Heart Failure Patients and the Importance of Neutrophil Gelatinase-Associated Lipocalin.

BACKGROUND/AIMS: The rate of incidence and prevalence of acute kidney injury is increasing due to an increased number of patients with heart failure. Therefore it is very pertinent to early detect the level of renal injuries and to make necessary heart failure predictions. Thus the aim of this study is to determine renal functions and prognosis stratification in chronic heart failure patients and importance of Neutrophil Gelatinase-Associated Lipocalin (NGAL), an early diagnostic marker of acute kidney injury, as well as stratification of cardiovascular risk in heart failure patients. METHODS: Data including age, gender, comorbidities and medical history of outpatients and hospitalized patients from Farmacology and NeuroHumoraL activation (FAR NHL) multicenter prospective registry comprising three Cardiological Centers in the Czech Republic were collected between 1st October 2014 and 30th November 2015. One-year follow-up data were collected in November 2016 in such a way that all patients had at least one-year data from the time of recruitment, but up to two years to the time of follow-up. One-year data were used for the whole set of patients while data up to 24 months were used with Kaplan-Meier's survival curves to analyse the patients' survival data. Blood samples were collected from the patients and basic parameters were evaluated in order to analyse Neutrophil gelatinase-associated lipocalin (NGAL) and plasma levels of N-terminal pro-brain natriuretic peptide (NT-ProBNP) using Lipocalin-2/NGAL Human ELISA kit (Bio Vendor, Czechia) and the Cobas E411 NT-proBNP Immunoassay kit (Roche Diagnostics, Indianapolis, IN, USA) respectively. Statistical analysis was further carried out to explain the level of significance of the evaluated parameters using Spearman Correlation, Mann Whitney or Kruskal-Wallis test and log-rank test. RESULTS: Out of 547 patients from Farmacology and NeuroHumoraL activation (FAR NHL) multicenter prospective registry with available data on hospitalizations, mortality, biomarkers and one-year follow-up that were recorded, there were 439 males (80.3%) with a median age of 66 years. At least one-month stable patients with left ventricle ejection fraction (LV EF) under 50% were recorded. The etiology of heart failure was ischemic heart disease in 54%, dilated cardiomyopathy in 40% and others in 6%. 69% patients were in New York Heart Association functional class II. There were 76 events (13.9%; all-cause mortality, acute heart failure hospitalization, left ventricle assist device implantation and orthotopic heart transplant) in the first 365 days of follow-up. The area under the receiver operating characteristic curve was higher for NT-proBNP (0.77) than the creatinine (0.57), NGAL (0.55) or creatinine clearance (0.54). In multivariable analyses, NT-proBNP (P= 0.001) and NGAL (P = 0.004) were significant predictors of events. Subjects with NT-proBNP and NGAL above the cut off value (NT-proBNP 1,121 pg/ml, NGAL 80 ng/ml) survived without any event in 55.7%, subjects with NT-proBNP and NGAL under the cut off value survived without any event in 90.5%, after two years (P = 0.001). CONCLUSION: The findings of the study showed that NGAL associated with NT-proBNP was a stronger predictor of the primary endpoint than NGAL or NT-proBNP alone. The level of NGAL was rising in hypertension, ischemia, anemia, hypoalbuminemia, diabetes or arrhythmias.

Increased microcirculatory heterogeneity in patients with obstructive sleep apnea.

INTRODUCTION: Obstructive sleep apnea (OSA) is the most common form of sleep disordered breathing and has been associated with major cardiovascular comorbidities. We hypothesized that the microcirculation is impaired in patients with OSA and that the magnitude of impairment correlates to OSA severity. METHODS: Subjects were consecutive patients scheduled for routine diagnostic polysomnography (PSG). OSA was defined by paradoxical rib cage movements together with abdominal excursions and by the apnea-hypopnea index (AHI) (events/hour; no apnea AHI<5; mild apnea 5≤AHI<15; moderate apnea 15≤AHI<30; severe apnea AHI ≥30). Sidestream darkfield imaging was used to assess the sublingual microcirculation. Recordings of sublingual microcirculation (5 random sites) were performed before and after overnight PSG. Data are summarized as mean (±SD); p values <0.05 were considered statistically significant. RESULTS: Thirty-three consecutive patients were included. OSA was diagnosed in 16 subjects (4 moderate, 12 severe). There was no significant difference in microcirculation between subjects with moderate OSA and without OSA. However, compared to subjects without OSA, subjects with severe OSA (AHI≥30) showed a significant decrease of microvascular flow index (-0.07±0.17 vs. 0.08±0.14; p = 0.02) and increase of microvascular flow index heterogeneity (0.06±0.15 vs. -0.06±0.11; p = 0.02) overnight. Multiple regression analysis (adjusted for age and gender) showed both decrease of flow and increase of flow heterogeneity associated with AHI (b = -0.41; F = 1.8; p = 0.04 and b = 0.43; F = 1.9; p = 0.03, respectively). CONCLUSION: Acute overnight microcirculatory changes are observed in subjects with severe OSA characterized by decreased flow and increased flow heterogeneity.

Differential likelihood of NSTEMI vs STEMI in patients with sleep apnea.

BACKGROUND: Sleep apnea (SA) is associated with intermittent hypoxemia that may lead to ischemic preconditioning in the myocardium. This potential cardioprotective effect of SA may play a role in the development of non-ST-elevation myocardial infarction (NSTEMI) versus ST-elevation myocardial infarction (STEMI) during acute ischemia. However, there is limited evidence about the relative prevalence of NSTEMI versus STEMI in SA patients. We therefore prospectively investigated the prevalence of these two types of MI in patients with SA. METHODS: We prospectively studied 782 consecutive patients admitted with the diagnosis of acute MI (both NSTEMI and STEMI). All subjects underwent sleep evaluations using a portable diagnostic device after at least 48h post-admission, provided they were in stable condition. Six hundred and seven out of 782 patients had technically adequate sleep studies, and therefore were included in the final analysis. RESULTS: SA was present in 65.7% (n=399) and NSTEMI in 30% (n=182) of patients. Increasing severity of SA was associated with increasing likelihood of NSTEMI, and with decreasing likelihood of STEMI (p<0.001). Relative frequency of NSTEMI in the moderate to severe SA group (AHI≥15events/h) was 40.6% versus 29.9% for STEMI (p=0.01). CONCLUSION: The prevalence of NSTEMI increases with increasing severity of SA. This finding may suggest a cardioprotective role of SA, which may attenuate the development of STEMI, perhaps through ischemic preconditioning.