Cardiovascular assessment after treatment for retinopathy of prematurity: a comparative study between anti-VEGF agent (aflibercept) and laser.

OBJECTIVE: The aim of this study was to compare the cardiac effects and aortic arterial indices following intravitreal aflibercept treatment or diode laser photocoagulation for the treatment of retinopathy of prematurity (ROP) in infants. METHODS: This single-centre, retrospective study was conducted in infants who were administered laser photocoagulation (LPC) or intravitreal aflibercept (IVA) treatment as initial treatment and had completed at least one year of corrected age. The patients were evaluated in terms of aortic elastic parameters, right and left ventricular systolic and diastolic function using conventional, pulsed Doppler and tissue Doppler imaging (TDI) echocardiographic parameters. RESULTS: Fifteen infants were in the LPC group, 16 in the IVA group, and 20 in the control group. Although there were some statistically significant differences in terms of pulsed and TDI echocardiographic parameters between the treatment and control groups, these values could not clearly be adopted as a diastolic dysfunction and myocardial performance indices were not influenced. The aortic elastic parameters were impaired in both LPC and IVA groups compared to the control group. Consequently, we observed only minor differences between the treatment groups, which may suggest subtle changes due to the anti-angiogenic treatment. CONCLUSIONS: Although favourable and promising outcomes were obtained with intravitreal injection of anti-vascular endothelial growth factor agents for the treatment of ROP, concerns have been raised about potential systemic side effects, including potential cardiovascular side effects caused by these agents. The small reduction in right ventricular Doppler velocities could probably be explained by the use of anti-angiogenic or laser treatment in infants.

Cardiovascular Risk Assessment in Pediatric Liver Transplant Patients.

OBJECTIVES: Cardiovascular (CV) diseases play a leading role in the mortality of adult liver transplant (LT) recipients. However, data regarding CV risk factors in children after LT remain sparse. The present study assessed the presence of CV risk factors and signs of CV impairment in LT children. METHODS: A total of 42 LT recipients (21 men, age 9.93 ±â€Š3.57 years) were studied. Body composition [body mass index standard deviation score, percentage of body fat (by bioimpedance analysis)], lipid profiles, glycemic control, blood pressure, and arterial stiffness [assessed by aortic pulse wave velocity (PWV)] were evaluated. The effect of different treatment modalities [tacrolimus (TAC) (n = 30) or cyclosporine (CyA) (n = 11)] was also analyzed. RESULTS: Almost 18% of children were overweight or obese. Patients on TAC had a significantly higher body fat mass and percentage of body fat compared with the CyA group (P < 0.02). Borderline to high lipid values were present in 40% of patients. Children on CyA had higher serum cholesterol levels compared to TAC (P < 0.004). Nineteen percent of patients had hypertension. Half of the patients had glomerular filtration rate values <90 mL/min/1.73 m, whereas PWV values were above the 95th percentile in 12%. CONCLUSIONS: Increased body fat, chronic kidney disease, high lipid content, hypertension, and increased arterial stiffness are already present and are in part related to the type of immunosuppression regimen in LT children >5 years following transplantation. Long-term follow-up is needed to evaluate their impact on CV health and survival.

The Assessment of Left Ventricle Function and Subclinical Atherosclerosis in Patients with Acute Myeloid Leukemia.

Aim To assess the onset of early left ventricular (LV) systolic and diastolic function impairment and the subclinical atherosclerosis following chemotherapy in patients diagnosed with acute myeloid leukemia (AML). MATERIALS AND METHODS: Thirty patients diagnosed with AML with no cardiac history, having LV ejection fraction (LVEF) >50%, were evaluated at baseline and 6 months after starting four cycles of chemotherapy. We measured LV function, global longitudinal strain and subclinical atherosclerosis markers: intima-media thickness (IMT), arterial stiffness aortic pulse wave velocity (PWVAo) and ankle-brachial index (ABI). RESULTS: LVEF had decreased at 6 months after treatment initialization (p<0.001), the same changes being observed for LV fraction shortening (p<0.001), mitral annular plane systolic excursion and S' wave (p<0.001 and p<0.05). Bilateral IMT and PWVAo significantly increased, 12 out of 30 patients (40%) had LVEF ≤50% after 6 months of chemotherapy, five of them receiving daunorubicin at more than 500 mg/m2/injection. CONCLUSION: LV function is impaired after 6 months of chemotherapy, with early changes of subclinical atherosclerosis becoming evident.

Longitudinal Assessment of Vascular Function With Sunitinib in Patients With Metastatic Renal Cell Carcinoma.

BACKGROUND: Sunitinib, used widely in metastatic renal cell carcinoma, can result in hypertension, left ventricular dysfunction, and heart failure. However, the relationships between vascular function and cardiac dysfunction with sunitinib are poorly understood. METHODS AND RESULTS: In a multicenter prospective study of 84 metastatic renal cell carcinoma patients, echocardiography, arterial tonometry, and BNP (B-type natriuretic peptide) measures were performed at baseline and at 3.5, 15, and 33 weeks after sunitinib initiation, correlating with sunitinib cycles 1, 3, and 6. Mean change in vascular function parameters and 95% confidence intervals were calculated. Linear regression models were used to estimate associations between vascular function and left ventricular ejection fraction, longitudinal strain, diastolic function (E/e'), and BNP. After 3.5 weeks of sunitinib, mean systolic blood pressure increased by 9.5 mm Hg (95% confidence interval, 2.0-17.1; P=0.02) and diastolic blood pressure by 7.2 mm Hg (95% confidence interval, 4.3-10.0; P<0.001) across all participants. Sunitinib resulted in increases in large artery stiffness (carotid-femoral pulse wave velocity) and resistive load (total peripheral resistance and arterial elastance; all P<0.05) and changes in pulsatile load (total arterial compliance and wave reflection). There were no statistically significant associations between vascular function and systolic dysfunction (left ventricular ejection fraction and longitudinal strain). However, baseline total peripheral resistance, arterial elastance, and aortic impedance were associated with worsening diastolic function and filling pressures over time. CONCLUSIONS: In patients with metastatic renal cell carcinoma, sunitinib resulted in early, significant increases in blood pressure, arterial stiffness, and resistive and pulsatile load within 3.5 weeks of treatment. Baseline vascular function parameters were associated with worsening diastolic but not systolic function.

[Shereshevsky-Turner syndrome: Estrogen replacement therapy and cardiovascular risk factors]. / Sindrom Shereshevskogo-Ternera: zamestitel'naia terapiia éstrogenami i faktory riska razvitiia serdechno-sosudistykh oslozhnenii.

AIM: To investigate the impact of menopausal hormone therapy (MHT) on the expression of risk factors for cardiovascular events (CVEs) in patients with Shereshevsky-Turner syndrome (STS); to elaborate an algorithm for patient management using MHT. SUBJECTS AND METHODS: From 2010 to 2012, a total of 41 patients aged 14 to 35 years with STS were examined in the framework of a prospective observational study. 100 STS case histories in 2000 to 2009 were retrospectively analyzed. The indicators of the so-called cardiometabolic risk, such as body mass index (BMI), lipidogram readings, venous plasma glucose levels, and blood pressure, were estimated in relation to the type of MHT. In the prospective part of the investigation, an angioscan was used to estimate vessel characteristics (stiffness, wall tone, endothelial function (EF)), by using the examination data. RESULTS: 90% of the patients with STS were found to have risk factors for CVEs: atherogenic dyslipidemia (85%; 51% in the general female population of the same age), diastolic hypertension (36%; no more than 5% that is not typical for age-matched healthy general female population). In addition to increased arterial wall stiffness (AWS), obvious EF disorder is typical for STS patients. MHT was accompanied by a dose-dependent (estradiol, at least 2 mg) reduction in diastolic blood pressure by an average of 13% over 24 months, an increase in high density lipoprotein levels by more than 10% over 24 months and also contributedto a decrease in AWS and an improvement in EF. CONCLUSION: By favorably affecting the EF of vessels and reducing the severity of atherogenic dyslipidemia, MHT potentially enables a reduction in CV risk in patients with STS.

Hypertensive Cardiovascular Risk: Pulsatile Hemodynamics, Gender, and Therapeutic Implications.

PURPOSE: In recent years, the predictive value of 2 pulsatile parameters has been extensively studied in hypertension: aortic stiffness and pulse pressure (PP) amplification. Aortic stiffness is an index of aortic rigidity and PP-amplification is the ratio between central and brachial PP, an indirect evaluation of wave reflections. Both are safe, independent, noninvasive predictors of overall and cardiovascular risk. Our purpose is to determine the validity of these parameters in 2 different circumstances: gender and therapeutic implications. AGE EFFECT: Studies have shown that whereas steady mean arterial pressure is significantly higher in men than in women, pulsatile pressure largely predominates in women, mostly in older age and as a consequence of short stature. Gender differences require more extensive investigation due to the disparities of dose-response ranging among populations and the contribution of ethnic factors, frequently based on individual origin. REGARDING THERAPEUTIC IMPLICATIONS: Many questions have yet to be resolved. First, the prognosis of antihypertensive therapy is largely based on blood pressure reduction but also requires evaluation of arterial rigidity and wave reflections to achieve adequate therapeutic "de-stiffening." The most effective approach appears to be the combination of angiotensin- and calcium-channel blockade, in certain cases associated with diuretic compounds. Second, antialdosterone drugs can be useful, but it is their antifibrotic more than their antihypertensive effect that appears effective. Third, prevention of comorbidities, such as those associating hypertension, diabetes, and/or kidney damage, should become primary targets for drug treatment.

Arterial (Aortic) Stiffness in Patients with Resistant Hypertension: from Assessment to Treatment.

PURPOSE OF REVIEW: The purpose of the review is to examine whether measurement of aortic stiffness could be especially value-adding for risk stratification and treatment among patients with resistant hypertension (RH). RECENT FINDINGS: Adverse arterial remodeling and increased aortic stiffness is associated with RH, and it may be of additional clinical benefit to measure aortic stiffness in these patients. However, there is insufficient evidence to determine whether aortic stiffness is excessively high relative to the level of blood pressure (BP) among people with RH. This issue needs resolution as it could help refine management decisions guided by aortic stiffness. If conventional antihypertensive therapy fails to lower BP in patients with RH, there is good rationale for effectiveness of spironolactone as add on therapy, and this should also improve aortic stiffness. Lifestyle intervention with exercise and diet should be additionally efficacious towards improving BP and aortic stiffness in patients with RH, but there is limited data in this patient population. For better characterization on the effects of BP treatment on aortic stiffness, measures of central aortic BP may help refine management decisions above and beyond conventional arm cuff BP. There is strong evidence to support the use of aortic stiffness as a tool to aid risk stratification in hypertension management. Although there is a theoretical basis for special additional benefit of measuring aortic stiffness in patients with RH (as distinct from uncomplicated hypertension), at this time, there is inadequate data available to make definitive conclusions and is an area for future investigation.

[Assessment of the Impact of Nicorandil on the Quality of Life and Prognosis Indicators in Patients With Stable Angina].

OBJECTIVE: To study the effect of nicorandil on the elasticity of the great vessels, cardiac functional parameters and quality of life in patients with coronary heart disease (CHD). MATERIAL AND METHODS: In a double-blind, randomized, placebo-controlled trial of nicorandil was attended by 154 patients with stable angina III functional class (FC), divided into 2 comparable age and sex group. Study duration was 12 months. RESULTS: In the group treated with nicorandil compared with placebo, the number of angina attacks and nitrate intake of short-significantly reduced, improved elastic properties of large arteries, improved quality of life. In a cohort of patients with CHD and left ventricular ejection fraction less than 45% nikorandil addition to standard therapy has improved the systolic function of the heart and reduce left ventricular remodeling. CONCLUSION: The use of nicorandil in addition to standard therapy can not only improve the quality of life in patients with coronary artery disease, but also a positive impact on the state of elasticity of blood vessels and morpho-functional parameters of the heart.

[Application of Methods of Assessment of Vascular Wall Stiffness in Clinical Practice: Capabilities of Cardio-Ankle Vascular Index].

This paper contains discussion of application of methods of assessment of vascular stiffness in clinical practice, comparison of such parameters as pulse wave velocity, ankle-brachial and cardio-ankle vascular index (CAVI), as well as analysis of advantages of cardio-ankle CAVI for diagnosis, evaluation of effectiveness of treatment, and prognosis in various cardiovascular diseases.

Comparison of atenolol versus bisoprolol with noninvasive hemodynamic and pulse wave assessment.

We aimed to compare atenolol versus bisoprolol regarding general hemodynamics, central-peripheral blood pressure (BP), pulse wave parameters, and arterial stiffness. In this open-label, crossover study, we recruited 19 hypertensives, untreated or with stable monotherapy. Patients were randomized to receive atenolol (25-50 mg) or bisoprolol (2.5-5 mg), and then switched medications after 4 weeks. Studies were performed at baseline and after each drug period. In pulse wave analyses, both drugs significantly increased augmentation index (P < .01) and ejection duration (P < .02), and reduced heart rate (P < .001), brachial systolic BP (P ≤ .01), brachial diastolic BP (P ≤ .001), and central diastolic BP (P ≤ .001), but not central systolic BP (P ≥ .06). Impedance cardiographic assessment showed a significantly increased stroke volume (P ≤ .02). There were no significant differences in the effects between drugs. In conclusion, atenolol and bisoprolol show similar hemodynamic characteristics. Failure to decrease central systolic BP results from bradycardia with increased stroke volume and an earlier reflected aortic wave.

In vivo assessment of arterial stiffness in the isoflurane anesthetized spontaneously hypertensive rat.

BACKGROUND: Rodent models are increasingly used to study the development and progression of arterial stiffness. Both the non-invasive Doppler derived Pulse Wave Velocity (PWV) and the invasively determined arterial elastance index (EaI) have been used to assess arterial stiffness in rats and mice, but the need for anesthetic agents to make these in vivo estimates may limit their utility. Thus, we sought to determine: 1) if known differences in arterial stiffness in spontaneously hypertensive rats (SHR) are detectable by PWV and EaI measurements when made under isoflurane anesthesia, and 2) if these two uniquely acquired assessments of arterial elasticity correlate. METHODS: We obtained PWV and EaI measurements in isoflurane anesthetized young and old SHRs, which are known to have significant differences in arterial stiffness. Doppler pulse waves were recorded from carotid and iliac arteries and the distance (D) between probe applantation sites was recorded. Simultaneously, an EKG was obtained, and the time intervals between the R-wave of the EKG to the foot of the Doppler waveforms were measured and averaged over three cardiac cycles. Pulse-transit time (T) of the carotid to iliac artery was determined, and PWV was calculated as Distance (D)/Time (T), where D = the distance from the carotid to the iliac notch and T = (R to iliac foot) - (R to carotid foot). EaI was subsequently determined from pressure volumes loops obtained via left ventricle catheterization. RESULTS: PWV and EaI were found to be significantly faster in the older rats (13.2 ± 2.0 vs. 8.0 ± 0.8 m/sec, p < 0.001; 120 ± 20 vs. 97 ± 16 mmHg/µl/g, p <0.05). Bland-Altman analyses of intra- and inter-observer measures demonstrate a statistically significant relationship between readings (p < 0.0001). PWV and EaI measurements were found to be significantly and positively correlated with a correlation coefficient of 0.53 (p < 0.05). CONCLUSION: Our study suggests that isoflurane administration does not limit Doppler PWV or EaI measures in their ability to provide accurate, in vivo assessments of relative arterial stiffness in isoflurane anesthetised SHR rats. Furthermore, PWV data obtained in these rats correlate well with invasively determined EaI.

Regulação autonômica das propriedades mecânicas em bioprótese valvar porcina / Autonomic regulation of mechanical properties in porcine mitral valve cusps / Regulación autonómica de las propiedades mecánicas en bioprótesis valvular porcina

FUNDAMENTO: A presença de nervos nas válvulas cardíacas foi demonstrada pela primeira vez há décadas e identificadas em subpopulações: simpáticas e parassimpáticas, e, portanto, é esperado que as válvulas sejam grandemente afetadas pelos nervos autônomos. Entretanto, poucos estudos têm se concentrado na regulação de válvulas cardíacas pelo sistema nervoso autônomo. OBJETIVO: Buscamos identificar o papel do sistema nervoso autônomo na regulação das propriedades mecânicas dos tecidos de válvulas mitrais porcinas. MÉTODOS: As propriedades mecânicas dos folhetos de válvulas mitrais porcinas foram avaliados em resposta à norepinefrina (NE) e acetilcolina (ACH), os principais neurotransmissores. Ao mesmo tempo, fentolamina (FENT), metoprolol (Metop), atropina (Atrop) e desnudamento endotelial foram adicionados ao sistema reativo. RESULTADOS: Sob condições fisiológicas, a rigidez não foi afetada pelo desnudamento endotelial (p > 0,05). A NE significantemente aumentou a rigidez valvar por aumento de 10 vezes na concentração (10-6 vs 10-7, p < 0,05; 10-5 vs 10-6, p < 0,05). Essa resposta foi amenizada por FENT, Metop ou desnudamento endotelial (p < 0,05); entretanto, manteve-se aumentada de maneira significante quando comparada aos Controles (p < 0,05). A ACH causou uma diminuição na rigidez acompanhada por um aumento em sua concentração (alteração significante na rigidez por aumento de 10 vezes na concentração de ACH, 10-6 vs Controle, p < 0,05; 10-5 vs 10-6, p < 0,05), que foi revertida pelo desnudamento endotelial e Atrop (p > 0,05 vs Controle). CONCLUSÃO: Esses achados ressaltam o papel do sistema nervoso autônomo na regulação das propriedades mecânicas das cúspides de válvula mitral porcina, o que reforça a importância do estado nervoso autônomo no funcionamento ideal da válvula.

BACKGROUND: The presence of nerves in heart valves was first depicted decades ago and identified into subpopulations: sympathetic, parasympathetic. So valves are expected to be greatly affected by the autonomic nerves. However, few studies have focused on the regulation of heart valves by the autonomic nervous system. OBJECTIVE: We sought to identify the role of the autonomic nervous system in the regulation of the mechanical properties of porcine mitral valve tissues. METHODS: Mechanical properties of porcine mitral valve leaflets were evaluated in response to norepinephrine (NE) and acetylcholine (ACH), the main neurotransmitters. At the same time, phentolamine (Phent), metoprolol (Metop), atropine (Atrop) and endothelial denudation were added to the reactive system. RESULTS: Under physiological conditions, the stiffness was not affected by endothelial denudation (p > 0.05). NE elevated the valve stiffness significantly per 10-fold increase in concentration (10-6 vs 10-7, p < 0.05; 10-5 vs 10-6, p < 0.05). This response was mitigated by Phent, Metop or endothelial denudation (p < 0.05), however, it was still increased significantly when compared to Controls (p < 0.05). ACH caused a decrease in stiffness accompanied by an increase in its concentration (significant change in stiffness per 10-fold increase in ACH concentration, 10-6 vs Control, p < 0.05; 10-5 vs 10-6, p < 0.05), which were reversed by endothelial denudation and Atrop (p > 0.05 vs Control). CONCLUSION: These findings highlight the role of the autonomic nervous system in the regulation of the mechanical properties of porcine mitral valve cusps, which underline the importance of autonomic nervous status for optimal valve function.

FUNDAMENTO: La presencia de nervios en las válvulas cardíacas quedó demostrada por primera vez hace algunas décadas e identificadas en sub-poblaciones: simpáticas y parasimpáticas y por lo tanto, lo que se espera es que las válvulas reciban una gran afectación de los nervios autónomos. Sin embargo, pocos estudios se han concentrado en la regulación de válvulas cardíacas a través del sistema nervioso autónomo. OBJETIVO: Buscamos identificar el papel del sistema nervioso autónomo en la regulación de las propiedades mecánicas de los tejidos de las válvulas mitrales porcinas. MÉTODOS: Las propiedades mecánicas de las capas de válvulas mitrales porcinas fueron evaluadas en respuesta a la norepinefrina (NE) y a la acetilcolina (ACH), los principales neurotransmisores. Igualmente, la fentolamina (FENT), el metoprolol (Metop), la atropina (Atrop) y la denudación endotelial también se añadieron al sistema reactivo. RESULTADOS: Bajo condiciones fisiológicas, la rigidez no se afectó por el denudación endotelial (p > 0,05). La NE aumentó significativamente la rigidez valvular con un aumento de 10 veces en la concentración (10-6 vs 10-7, p < 0,05; 10-5 vs 10-6, p < 0,05). Esa respuesta fue amenizada por FENT, Metop o denudación endotelial (p < 0,05); pero se mantuvo aumentada de manera significativa cuando se le comparó con los Controles (p < 0,05). La ACH causó una disminución en la rigidez acompañada por un aumento en su concentración (alteración significativa en la rigidez por el aumento en 10 veces de la concentración de ACH, 10-6 vs Control, p < 0,05; 10-5 vs 10-6, p < 0,05), que fue revertida por la denudación endotelial y Atrop (p > 0,05 vs Control). CONCLUSIÓN: Esos hallazgos destacan el rol del sistema nervioso autónomo en la regulación de las propiedades mecánicas de las cúspides de la válvula mitral porcina, lo que refuerza la importancia del estado nervioso autónomo en el funcionamiento ideal de la válvula.