Obesity-Related Hemodynamic Alterations in Patients with Cushing's Disease.

Background: Cushing's disease (CD) is associated with a specific form of metabolic syndrome that includes visceral obesity, which may affect cardiovascular hemodynamics by stimulating hypercortisolism-related metabolic activity. The purpose of this study was to evaluate the relationship between obesity and the hemodynamic profile of patients with CD. Methods: This prospective clinical study involved a hemodynamic status assessment of 54 patients newly diagnosed with CD with no significant comorbidities (mean age of 41 years). The assessments included impedance cardiography (ICG) to assess such parameters as stroke index (SI), cardiac index (CI), velocity index (VI), acceleration index (ACI), Heather index (HI), systemic vascular resistance index (SVRI), and total arterial compliance index (TACI) as well as applanation tonometry to assess such parameters as central pulse pressure (CPP) and augmentation index (AI). These assessments were complemented by echocardiography to assess cardiac structure and function. Results: Compared with CD patients without obesity, individuals with CD and obesity (defined as a body mass index ≥ 30 kg/m2) exhibited significantly lower values of ICG parameters characterizing the pumping function of the heart (VI: 37.0 ± 9.5 vs. 47.2 ± 14.3 × 1*1000-1*s-1, p = 0.006; ACI: 58.7 ± 23.5 vs. 76.0 ± 23.5 × 1/100/s2, p = 0.005; HI: 11.1 ± 3.5 vs. 14.6 ± 5.5 × Ohm/s2, p = 0.01), whereas echocardiography in obese patients showed larger heart chamber sizes and a higher left ventricular mass index. No significant intergroup differences in blood pressure, heart rate, LVEF, GLS, TACI, CPP, or AI were noted. Conclusions: Hemodynamic changes associated with obesity already occur at an early stage of CD and manifest via significantly lower values of the ICG parameters illustrating the heart's function as a pump, despite the normal function of the left ventricle in echocardiography.

The Heart's Function as a Pump Assessed via Impedance Cardiography and the Autonomic System Balance in Patients with Early-Stage Acromegaly.

BACKGROUND: Acromegaly is a rare, chronic disease that involves structural and functional abnormalities of the cardiovascular system. Acromegaly likely affects interactions between the cardiovascular system and the autonomic nervous system (ANS). Therefore, assessing the relationship between sympathetic-parasympathetic balance by analyzing heart rate variability (HRV) and the hemodynamic profile via impedance cardiography (ICG) may be useful in learning the exact nature of interactions between the ANS and the cardiovascular system. The purpose of this study was to assess a possible association between HRV and ICG-based parameters of cardiac function in patients newly diagnosed with acromegaly. METHODS: This observational cohort study was conducted on 33 patients (18 men, mean age of 47 years) newly diagnosed with acromegaly and no significant comorbidities. A correlation analysis (Spearman's rank coefficient R) of the parameters assessed via ICG and the HRV assessed via 24 h ambulatory electrocardiography was performed. ICG assessments included the following parameters: stroke volume index (SI), cardiac index (CI), acceleration index (ACI), velocity index (VI), and Heather index (HI). The analysis of HRV included both time-domain parameters (pNN50, SDNN, SDSD, rMSSD) and frequency-domain parameters (total power (TP) and its individual frequency bands: low-frequency (LF day/night), high-frequency (HF day/night), and the LF/HF ratio (day/night)). RESULTS: Frequency-domain HRV analysis showed the following correlations: (1) lower nighttime LF values with higher ACI (R = -0.38; p = 0.027) and HI (R = -0.46; p = 0.007) values; (2) higher nighttime HF values with higher ACI (R = 0.39; p = 0.027) and HI (R = 0.43; p = 0.014) values; (3) lower nighttime LF/HF values with higher ACI (R = -0.36; p = 0.037) and HI (R = -0.42; p = 0.014) values; (4) higher nighttime TP values with higher SI values (R = 0.35; p = 0.049). Time-domain parameters of HRV showed a significant correlation only between the nighttime values of SDSD and SI (R = 0.35; p = 0.049) and between the daytime and nighttime values of SDNN and HR (R = -0.50; p = 0.003 and R = -0.35; p = 0.046). In multivariate regression, only ACI was revealed to be independently related to HRV. CONCLUSIONS: In patients newly diagnosed with acromegaly, the relationship between the sympathetic-parasympathetic balance assessed via HRV and the hemodynamic profile assessed via ICG was revealed. Better function of the left ventricle was associated with a parasympathetic shift in the autonomic balance.

The patient's sex determines the hemodynamic profile in patients with Cushing disease.

Background: Cushing disease (CD) may lead to accelerated cardiovascular remodeling and increased mortality. There are suspected differences in the mechanism of cardiovascular dysfunction between males and females with CD. The purpose of this study was to assess the effect of patient sex on the hemodynamic profile assessed via impedance cardiography and echocardiography in patients newly diagnosed with CD. Material and methods: The 54 patients newly diagnosed with CD (mean age 41 years; 77.8% of females) who were included in this prospective clinical study underwent impedance cardiography to assess specific parameters (including systemic vascular resistance index [SVRI], total arterial compliance index [TACI], Heather index [HI], stroke index [SI], cardiac index [CI], velocity index [VI], and acceleration index [ACI]) and transthoracic echocardiography to assess heart chamber diameters and left ventricular systolic and diastolic function. Results: Males with CD exhibited higher afterload, with higher SVRI (3,169.3 ± 731.8 vs. 2,339.3 ± 640.8 dyn*s*cm-5*m² in males and females, respectively; p=0.002), lower TACI (0.80 ± 0.30 vs. 1.09 ± 0.30 mL/mmHg*m2; p=0.008), and lower hemodynamic parameters of left ventricular function, with lower HI (9.46 ± 2.86 vs. 14.1 ± 5.06 Ohm/s2; p=0.0007), lower VI (35.1 ± 11.9 vs. 44.9 ± 13.1 1*1000-1*s-1; p=0.009), lower SI (36.5 ± 11.7 vs. 43.6 ± 9.57 mL/m2; p=0.04), lower CI (2.36 ± 0.46 vs. 3.17 ± 0.76 mL*m-2*min-1; p=0.0009), and lower ACI (50.4 ± 19.8 vs. 73.6 ± 25.0 1/100/s2; p=0.006). There were no significant differences between the sexes in left ventricular systolic or diastolic function assessed by echocardiography. Conclusion: In comparison with females with CD, males with CD have a less favorable hemodynamic profile, with higher afterload and worse left ventricular function. Sex differences in cardiovascular system function should be taken into consideration in designing personalized diagnostic and therapeutic management of patients with CD.

Increased Thoracic Fluid as the Most Distinctive Cardiovascular Hemodynamic Alteration in Men with Prolactinoma.

Hyperprolactinemia in males with prolactin-secreting adenomas, or prolactinomas, may be associated with endothelial dysfunction and co-existing cardiovascular risk factors. As a noninvasive technique of assessing cardiac function, impedance cardiography (ICG) may be useful in the early detection of hemodynamic dysfunction. The aim of the present study was to analyze and compare the hemodynamic profiles of patients with prolactinoma versus controls. A total of 20 men with prolactinoma (PR group) (mean age 43 years) and 20 men from the control group (CG) were evaluated in this prospective, observational comparative clinical study. The study subjects were propensity score-matched in terms of clinical characteristics­age, mean blood pressure [MBP], arterial hypertension [AH] rates, and body mass index [BMI]. ICG assessments of hemodynamic profiles were conducted with the use of a Niccomo™ device and included stroke volume index (SI), cardiac index (CI), systemic vascular resistance index (SVRI), velocity index (VI), acceleration index (ACI), Heather index (HI), and thoracic fluid content (TFC). AH was well-controlled in both study groups (116/76 mmHg PR vs. 119/76 mmHg CG). In comparison with CG patients, ICG revealed PR group patients to have higher rates of high thoracic fluid content (TFC) (>35 1/kOhm; p = 0.035) and lower SI values (<35 mL/m2, p = 0.072). There was a convergent tendency towards lower values of other cardiac function parameters (SI, CI, VI, ACI, and HI). Prolactinoma-associated endocrine abnormalities are related to hemodynamic profile alterations, including higher rates of increased TFC and the risk of worsened cardiac function.

Cushing's Disease: Assessment of Early Cardiovascular Hemodynamic Dysfunction With Impedance Cardiography.

Background: Cushing's disease is a rare condition associated with a high cardiovascular risk and hypercortisolemia-related hemodynamic dysfunction, the extent of which can be assessed with a noninvasive method, called impedance cardiography. The standard methods for hemodynamic assessment, such as echocardiography or ambulatory blood pressure monitoring may be insufficient to fully evaluate patients with Cushing's disease; therefore, impedance cardiography is being currently considered a new modality for assessing early hemodynamic dysfunction in this patient population. The use of impedance cardiography for diagnosis and treatment of Cushing's disease may serve as personalized noninvasive hemodynamic status assessment and provide a better insight into the pathophysiology of Cushing's disease. The purpose of this study was to assess the hemodynamic profile of Cushing's disease patients and compare it with that in the control group. Material and Methods: This observational prospective clinical study aimed to compare 54 patients with Cushing's disease (mean age 41 years; with 64.8% of this population affected with arterial hypertension) and a matched 54-person control group (mean age 45 years; with 74.1% of this population affected with arterial hypertension). The hemodynamic parameters assessed with impedance cardiography included the stroke index (SI), cardiac index (CI), systemic vascular resistance index (SVRI), velocity index (VI), (ACI), Heather index (HI), and thoracic fluid content (TFC). Results: The Cushing's disease group was characterized by a higher diastolic blood pressure and a younger age than the control group (82.9 vs. 79.1 mmHg, p=0.045; and 41.1 vs. 44.9 years, p=0.035, respectively). Impedance cardiography parameters in the Cushing's disease group showed: lower values of SI (42.1 vs. 52.8 ml/m2; p ≤ 0.0001), CI (2.99 vs. 3.64 l/min/m2; p ≤ 0,0001), VI (42.9 vs. 52.1 1/1000/s; p=0.001), ACI (68.7 vs. 80.5 1/100/s2; p=0,037), HI (13.1 vs. 15.2 Ohm/s2; p=0.033), and TFC (25.5 vs. 27.7 1/kOhm; p=0.006) and a higher SVRI (2,515 vs. 1,893 dyn*s*cm-5*m2; p ≤ 0.0001) than those in the control group. Conclusions: Cushing's disease is associated with significantly greater vasoconstriction and left ventricular systolic dysfunction. An individual assessment with impedance cardiography may be useful in Cushing's disease patients in order to identify subclinical cardiovascular complications of chronic hypercortisolemia as potential therapeutic targets.

Acromegaly: The Research and Practical Value of Noninvasive Hemodynamic Assessments via Impedance Cardiography.

Background: Arterial hypertension (AH) that accompanies acromegaly (AC) may lead to cardiovascular dysfunction. Such consequences may be detected with impedance cardiography (ICG), which is a noninvasive method of hemodynamic assessment. Early detection of subclinical hemodynamic alterations in AC patients may be crucial for optimizing treatment and preventing cardiovascular remodeling. The purpose of this study was to identify the hemodynamic parameters of the cardiovascular system that differentiate patients with AC from those in the control group (CG), with a particular emphasis on potential targets for medical therapy. Methods: This observational, prospective, clinical study involved a comparative analysis of 33 AC patients with no significant comorbidities and the controls selected via propensity score matching based on a set of baseline characteristics (age, sex, body mass index, mean blood pressure [MBP]), with comparable proportions of AH patients. The assessed hemodynamic parameters included the stroke volume index (SI), cardiac index, systemic vascular resistance index, velocity index (VI), acceleration index, Heather index (HI), and thoracic fluid content (TFC). Results: Both the AC group and the CG had well-controlled AH (mean blood pressure of 121/77 mmHg and 119/76 mmHg, respectively). In terms of baseline characteristics, the AC group was characterized by a higher hear rate and lower creatinine levels than the CG (76.2 bpm vs. 66.8 bpm [p = 0.001] and 0.755 mg/dL vs. 0.850 mg/dL [p = 0.035], respectively). ICG assessment of AC patients and CG patients showed the former to have higher heart rates (73.5 bpm vs. 65.2 bpm; p = 0.003), lower SI (43.8 mL/m2 vs. 53.4 mL/m2; p = 0.0001), lower VI (42.1 1/1000/s vs. 49.3 1/1000/s; p = 0.037), lower HI (8.49 Ohm/s2 vs. 13.4 Ohm/s2, p ≤ 0.0001), and higher thoracic fluid content (TFC) (38.4 1/kOhm vs. 28.1 1/kOhm; p ≤ 0.0001), respectively. Conclusions: Even with well-controlled hypertension, AC is associated with a high TFC, increased heart rate, and decreased indices of cardiac contractility. Hemodynamic changes in AC patients may be detected with the modern, noninvasive diagnostic tool, ICG.

Association of Central Sleep Apnea with Impaired Heart Structure and Cardiovascular Hemodynamics in Patients with Chronic Heart Failure.

BACKGROUND Advanced heart failure (HF) is commonly accompanied by central sleep apnea (CSA) with Cheyne-Stokes respiration (CSR). The aim of this study was to evaluate the relationship between CSA/CSR and other clinical features of HF, with particular emphasis on cardiovascular hemodynamics. MATERIAL AND METHODS In 161 stable HF patients with left ventricular ejection fraction (LVEF) ≤45% (NYHA class I-III; mean LVEF 32.8%) the clinical evaluation included: LVEF; left and right ventricular end-diastolic diameter (LVDd, RVDd); ratio of early transmitral flow velocity to early diastolic septal mitral annulus velocity (E/e') assessed by echocardiography; stroke index (SI); heart rate (HR); cardiac index (CI); and systemic vascular resistance index (SVRI) assessed by impedance cardiography (ICG). The comparison was performed between 2 subgroups: one with moderate/severe CSA/CSR - CSR_ [+] (n=51), and one with mild or no CSA/CSR - CSR_ [-] (n=110). RESULTS CSR_ [+] patients presented more advanced NYHA class (p<0.001) and more frequently had permanent atrial fibrillation (p=0.018). Moreover, they had: lower LVEF (p<0.0001); higher LVDd (p<0.0001), RVDd (p<0.001), and E/e' (p<0.001); lower SI (p<0.001) and CI (p=0.009); and higher HR (p=0.044) and SVRI (p=0.016). The following predictors of CSR_ [+] were identified: NYHA class (OR=3.34 per class, p<0.001, which was the only independent predictor); atrial fibrillation (OR=2.29, p=0.019); RV enlargement (OR=2.75, p=0.005); LVEF<35% (OR=3.38, p=0.001); E/e' (OR=3.15; p=0.003); and SI<35 ml/m2 (OR=2.96, p=0.003). CONCLUSIONS Presence of CSA/CSR in HF is associated with NYHA class, atrial fibrillation and more advanced impairment of cardiovascular structure and hemodynamics. Patient functional state remains the main determinant of CSR.

Sleep-disordered breathing in patients with heart failure: new trends in therapy.

Heart failure (HF) is a growing health problem which paradoxically results from the advances in the treatment of etiologically related diseases (especially coronary artery disease). HF is commonly accompanied by sleep-disordered breathing (SDB), which may directly exacerbate the clinical manifestations of cardiovascular disease and confers a poorer prognosis. Obstructive sleep apnoea predominates in mild forms while central sleep apnoea in more severe forms of heart failure. Identification of SDB in patients with HF is important, as its effective treatment may result in notable clinical benefits to the patients. Continuous positive airway pressure (CPAP) is the gold standard in the management of SDB. The treatments for central breathing disorders include CPAP, bilevel positive airway pressure (BPAP), and adaptive servoventilation (ASV), with the latter being the most modern method of treatment for the Cheyne-Stokes respiration and involving ventilation support with a variable synchronisation dependent on changes in airflow through the respiratory tract and on the patient's respiratory rate. ASV exerts the most favourable effect on long-term prognosis. In this paper, we review the current state of knowledge on the diagnosis and treatment of SDB with a particular emphasis on the latest methods of treatment.

Fractioned exhaled nitric oxide (FE(NO)) is not a sufficiently reliable test for monitoring asthma in pregnancy.

It has been reported that fractioned exhaled nitric oxide (FENO) can be used for monitoring airway inflammation and for asthma management but conclusions drawn by different researchers are controversial. The aim of our study was to evaluate the clinical usefulness of FENO assessment for monitoring asthma during pregnancy. We monitored 72 pregnant asthmatics aged 18-38years (Me=29 years) who underwent monthly investigations including: the level of asthma control according to GINA (Global Initiative for Asthma), the occurrence of exacerbations, ACT (Asthma Control Test), as well as FENO and spirometry measurements. In 50 women, during all visits, asthma was well-controlled. In the remaining 22 women, asthma was periodically uncontrolled. FENO measured at the beginning of the study did not show significant correlation with retrospectively evaluated asthma severity (r=0.07; p=0.97). An analysis of data collected during all 254 visits showed that FENO correlated significantly but weakly with ACT scores (r=0.25; p=0.0004) and FEV1 (r=0.21; p=0.0014). FENO at consecutive visits in women with well-controlled asthma (N=50) showed large variability expressed by median coefficient of variation (CV)=32.0% (Min 2.4%, Max 121.9%). This concerned both: atopic and nonatopic groups (35.5%; and 26.7%, respectively). Large FENO variability (35.5%) was also found in a subgroup of women (N=11) with ACT=25 constantly throughout the study. FENO measured at visits when women temporarily lost control of asthma (N=22; 38 visits), showed an increasing tendency (64.2 ppb; 9.5 ppb-188.3 ppb), but did not differ significantly (p=0.13) from measurements taken at visits during which asthma was well-controlled (27.6 ppb; 6.2 ppb-103.4 ppb). The comparison of FENO in consecutive months of pregnancy in women who had well-controlled asthma did not show significant differences in FENO values during the time of observation. The assessment of asthma during pregnancy by means of monitoring FENO is of limited practical value due to this parameter's considerable intrasubject variability, regardless of the degree of asthma control.

[The long-term variability of FeNO in pregnant asthmatic women with controlled asthma]. / Dlugoterminowa zmiennosc stezenia tlenku azotu w wydychanympowietrzu (FeNO) w astmie kontrolowanej u kobiet w ciazy.

INTRODUCTION: Fractional exhaled nitric oxide (FeNO) is considered as a useful, noninvasive marker of airway inflammation in asthma and allergic rhinitis. It has also been suggested that anti-inflammatory treatment guided by monitoring of exhaled NO could improve overall asthma control. However, long-term intra-subject variability of this parameter as well as the rate of its change, which can be clinically significant, have not been established yet. The aim of our study was to assess the long-term variability of FeNO in pregnant asthmatic women with controlled asthma. MATERIAL AND METHODS: Pregnant, non-smoking women with asthma were recruited between 3 and 6 months of gestation. Exhaled nitric oxide (FeNO) spirometric parameters were measured, and the asthma control test (ACT) was completed during monthly visits up to delivery. The data of 26 subjects with well-controlled asthma during pregnancy (ACT values within the range 20-25, normal spirometric parameters, stable treatment) were analysed. The variability of FeNO values was assessed using the variation coefficient CV (standard deviation x 100%/arithmetic mean). RESULTS: The median level of FeNO coefficient of variation (CV) was: 33.8% (range 11.3 to 121.9) in all subjects with well-controlled asthma during pregnancy. There were no statistically significant differences in FeNO variability between groups of patients who had at least one measurement of FeNO higher than 50ppb (39%; 11.8-121.9%) and those with all FeNO values below 50ppb (29.9%; 11.3-71.8%), as well as between atopic (35.7%; 11.8-121.9%) and nonatopic (24.2%; 11.3-71.8%) pregnant asthmatics (p = 0.95 and 0.11, respectively). CONCLUSIONS: High long-term variability of fractional exhaled nitric oxide values revealed in pregnant women with well-controlled asthma indicates that changes in this parameter should be interpreted with caution while being used for asthma treatment monitoring.

A case of Cushing's syndrome in pregnancy.

Cushing's syndrome (also known as hypercortisolemia) is rare in pregnant women due to the menstrual disturbances and infertility in women with hypercortisolism. A diagnosis of pathological hypercortisolism in pregnant women is often difficult as some symptoms of the disease may be associated with a complicated pregnancy. Hypercortisolemia leads to serious complications for mother and foetus, and is associated with premature labour and high foetal mortality. Hormonal and radiological diagnostics in pregnancy are limited. The results of hormonal measurements and dynamic tests are difficult to interpret due to the physiological changes in the hypothalamo-pituitaryadrenal axis connected with pregnancy. The optimal time and method of treatment should be chosen cautiously case by case because of the possibility of maternal and foetal complications. In this paper, we present a case of Cushing's syndrome secondary to adrenal adenoma in which the diagnosis was made in the 22(nd) week of pregnancy. Due to the advanced gestational status and mild symptoms of hypercortisolism, only symptomatic treatment was introduced. The patient was under continuous obstetric and endocrinological care. At 35 weeks of gestation, the pregnancy was terminated by emergency caesarean section because of premature detachment of the placenta. A male infant weighing 2,450 g was delivered; neither adrenal insufficiency in the child nor hypercortisolemia complications in the mother were observed.

Resolution of exercise oscillatory ventilation with adaptive servoventilation in patients with chronic heart failure and Cheyne-Stokes respiration: preliminary study.

BACKGROUND: Exercise oscillatory ventilation (EOV) is a common pattern of breathing in heart failure (HF) patients, and indicates a poor prognosis. AIM: To investigate the effects of adaptive servoventilation (ASV) on ventilatory response during exercise. METHODS: We studied 39 HF patients with left ventricular ejection fraction (LVEF) £ 45. Cardiorespiratory polygraphy, cardiopulmonary exercise testing (CPET), echocardiography, and measurement of N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration were performed. Twenty patients with Cheyne-Stokes respiration and apnoea-hypopnoea index (AHI) ≥ 15/h were identified. Of these, 11 patients were successfully titrated on ASV and continued therapy. In the third month of ASV treatment, polygraphy, CPET, echocardiography, and measurement of NT-proBNP concentration were performed again. RESULTS: The EOV was detected at baseline in 12 (31%) HF patients, including eight (67%) who underwent ASV. The EOV was associated with significantly lower LVEF, peak oxygen uptake (VO(2)), and ventilatory anaerobic threshold (VAT), and a significantly higher left ventricular diastolic diameter (LVDD), slope of ventilatory equivalent for carbon dioxide (VE/VCO(2)), AHI, central AHI and NT-proBNP concentration. In seven patients with EOV, reversal of EOV in the third month of ASV therapy was observed; only in one patient did EOV persist (p = 0.0156). CONCLUSIONS: The EOV can be reversed with ASV therapy. The EOV in association with central sleep apnoea and Cheyne- -Stokes respiration (CSA/CSR) is prevalent in HF patients and correlates with severity of the disease.