Combined pre- and post-capillary pulmonary hypertension in left heart disease.

Patients with heart failure (HF) often have pulmonary hypertension (PH), which is mainly post-capillary; however, some of them also develop a pre-capillary component. The exact mechanisms leading to combined pre- and post-capillary PH are not yet clear, but the phenomenon seems to start from a passive transmission of increased pressure from the left heart to the lungs, and then continues with the remodeling of both the alveolar and vascular components through different pathways. More importantly, it is not yet clear which patients are predisposed to develop the disease. These patients have some characteristics similar to those with idiopathic pulmonary arterial hypertension (e.g., young age and frequent incidence in female gender), but they share cardiovascular risk factors with patients with HF (e.g., obesity and diabetes), with both reduced and preserved ejection fraction. Thanks to echocardiography parameters and newly introduced scores, more tools are available to distinguish between idiopathic pulmonary arterial hypertension and combined PH and to guide patients' management. It may be hypothesized to treat patients in whom the pre-capillary component is predominant with specific therapies such as those for idiopathic pulmonary arterial hypertension; however, no adequately powered trials of PH-specific treatment are available in combined PH. Early evidence of clinical benefit has been proven in some trials on phosphodiesterase type 5 inhibitors, while data on prostacyclin analogues, endothelin-1 receptor antagonists, and soluble guanylate cyclase stimulators are still controversial.

Relationship between endothelial dysfunction, videocapillaroscopy and circulating CD3+CD31+CXCR4+ lymphocytes in systemic lupus erythematosus without cardiovascular risk factors.

OBJECTIVE: The objective of this paper is to analyse whether digital capillary morphology, analysed by nailfold videocapillaroscopy (NVC), and the number of circulating CD3 + CD31 + CXCR4 + lymphocytes (angiogenic T cells) could be markers of endothelial dysfunction (ED) in systemic lupus erythematosus (SLE) without cardiovascular disease (CVD) and CV risk factors. METHODS: Nineteen consecutive SLE patients, according to Systemic Lupus International Collaborating Clinics Classification Criteria, with a disease duration less than five years, low disease activity, without CVD and CV risk factors (diabetes, chronic renal disease, uncontrolled systemic arterial hypertension, smoking, hypercholesterolemia, obesity), statin or beta-blocker use were enrolled. Each patient and sex- and age-matched healthy control (HC) underwent Doppler echocardiogram, an endothelial function study by peripheral arterial tonometry technique, NVC and peripheral blood immunophenotyping. RESULTS: SLE ED+ more frequently showed NVC abnormalities compared with HCs ( p < 0.0001) in terms of minor alterations ( p = 0.017), lower capillary numbers ( p = 0.0035) and major alterations. SLE ED + showed a higher rate of CD3 + CD31 + CXCR4 + lymphocytes compared with SLE ED- and with HCs. NVC + SLE showed a significantly reduced rate of total CD3 + cells, but a higher rate and absolute number of CD3 + CD31 + CXCR4 + , compared with NVC- SLE. CONCLUSION: NVC alterations are frequent in SLE without any CV risk factors and CVD. They are associated with ED and increased circulating CD3 + CD31 + CXCR4 + lymphocytes. These findings demonstrate a clear microvascular perturbation in patients with short disease duration, low disease activity and no CV risk factors.

Ultrasound evaluation of left ventricular and aortic fibrosis after pre-eclampsia.

OBJECTIVES: Myocardial fibrosis is associated with adverse clinical outcome in adults. Our aim was to investigate using echocardiographic calibrated integrated backscatter (cIBS) the presence of myocardial and/or aortic fibrosis in asymptomatic women with a history of early-onset (EO) or late-onset (LO) pre-eclampsia (PE). METHODS: Thirty non-pregnant women whose most recent pregnancy was complicated by EO-PE, 30 with previous LO-PE pregnancy and 30 controls who had experienced only uncomplicated pregnancy previously were selected retrospectively from our electronic database and recalled between 6 months and 4 years after delivery. Data regarding gestational age (GA) and mean uterine artery (UtA) pulsatility index (PI) at diagnosis of PE were collected from their medical records. The women underwent cardiovascular assessment, during which the presence of fibrosis was investigated, by means of cIBS, at the basal interventricular septum (cIBSIVS ), the basal posterior wall (cIBSPW ) and the anterior wall of the ascending aorta, 3 cm above the valve (cIBSAO ). These findings were compared between the three patient groups. RESULTS: Using cIBS imaging, we found significant left ventricular (LV) fibrosis in women with a history of EO-PE compared with those with previous LO-PE pregnancy and controls (intergroup ANOVA P < 0.001 for cIBSIVS and P = 0.005 for cIBSPW ), whereas aortic fibrosis did not differ significantly among cases and controls. Stepwise multivariate regression analysis showed that LV fibrosis was associated independently with lower GA and higher mean UtA-PI at diagnosis of PE, while cIBSAO correlated with aortic diameters, stiffness and ventricular-arterial coupling. CONCLUSIONS: Women with a history of EO-PE show LV fibrosis in the short-medium term after delivery compared with women with previous LO-PE pregnancy and controls. LV fibrosis is associated with GA and mean UtA-PI at onset of PE. Larger studies using cardiac magnetic resonance imaging are needed to validate and confirm our findings. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Maternal cardiac function after HELLP syndrome: an echocardiography study.

OBJECTIVE: To evaluate maternal hemodynamics in asymptomatic women with a previous pregnancy affected by hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome and compare the findings to those of women with previous pre-eclampsia (PE) and controls with a previous uncomplicated pregnancy. METHODS: Women with a history of PE (n = 60) or HELLP syndrome (n = 49) and matched healthy controls (n = 60) underwent echocardiography at 6 months to 4 years after delivery, recording left ventricular (LV) dimensions, ejection fraction (LVEF) and mass, right ventricular (RV) tricuspid annular plane systolic excursion and fractional area change (FAC). Diastolic filling (E/A and E/E' ratios) and tissue Doppler imaging were evaluated for both ventricles and the myocardial performance index was calculated. RESULTS: Only women with previous HELLP syndrome showed significant LV concentric hypertrophy (20.4%). However, in both HELLP and PE groups, LV concentric remodeling (46.9% and 46.7%, respectively), diastolic dysfunction (expressed as altered E/A and E/E' ratios) and reduced LVEF (14.3% and 21.7%, respectively) were documented. RV variables did not differ significantly between cases and controls, except for FAC and E/E' ratio, which were slightly impaired in women with previous HELLP syndrome compared to those with previous PE (16.3% vs 10.0%, P = 0.04; 14.3% vs 3.3%, P = 0.03, respectively). CONCLUSIONS: The significant overlap of echocardiographic features in women with previous PE and HELLP syndrome suggests that these two conditions share the same pathophysiology. However, HELLP syndrome may lead to more severe cardiovascular remodeling in the short to medium term after delivery. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Endothelial dysfunction and vascular stiffness in women with previous pregnancy complicated by early or late pre-eclampsia.

OBJECTIVES: Pre-eclampsia (PE) is associated with an increased cardiovascular risk later in life. The persistence of endothelial dysfunction after delivery may represent the link between PE and cardiovascular disease. We aimed to evaluate endothelial function and arterial stiffness after delivery of pregnancy complicated by early-onset (EO) or late-onset (LO) PE and their correlation with gestational age and mean uterine artery pulsatility index at PE diagnosis and birth-weight percentile. METHODS: The study included 30 women with previous EO-PE, 30 with previous LO-PE and 30 controls with no previous PE. Participants were examined at between 6 months and 4 years after delivery. All included women were free from cardiovascular risk factors and drugs. Data on demographic and clinical characteristics during pregnancy were collected retrospectively from obstetrical charts. Endothelial function and arterial stiffness were assessed by peripheral arterial tonometry and pulse-wave analysis. RESULTS: All vascular parameters were significantly different, indicating circulatory impairment, in women with previous EO-PE. Women with previous LO-PE had higher vascular rigidity than did controls and all had normal values of reactive hyperemia index, although they were significantly lower when compared with those of controls. On multivariate analysis, gestational age and mean uterine artery pulsatility index at the time of PE diagnosis, and birth-weight percentile were all statistically related to the vascular indices studied, after correcting for confounding parameters. CONCLUSIONS: Women with previous pregnancy complicated by PE, in particular those with early-onset disease, showed persistent microcirculatory dysfunction, as suggested by a significant reduction in reactive hyperemia index value, and increased arterial stiffness. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Maternal endothelial function and vascular stiffness after HELLP syndrome: a case-control study.

OBJECTIVES: To assess endothelial function and arterial stiffness in women with a previous pregnancy complicated by pre-eclampsia (PE) with hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome, and to compare these findings to those in women with previous PE but no HELLP and to those in controls with previous uncomplicated pregnancy, in order to investigate the influence of HELLP syndrome on subsequent cardiovascular impairment. METHODS: In this prospective single-center case-control study, we performed peripheral arterial tonometry (PAT) (using the EndoPAT method) and pulse-wave velocity (PWV) assessment in 109 women who had had a singleton pregnancy complicated by PE with (n = 49) or without (n = 60) HELLP syndrome, as well as in 60 controls with previous uncomplicated pregnancy, between 6 months and 4 years after delivery. The following EndoPAT and PWV indices were compared between groups: reactive hyperemia index (RHI), as an indication of endothelial function, and peripheral and aortic heart-rate-corrected augmentation indices (AIx) standardized for a heart rate of 75 bpm (AIx@75) and carotid-femoral pulse-wave velocity (cfPWV), as indications of arterial stiffness. RESULTS: PAT and arterial stiffness indices were significantly different between PE cases, with or without previous HELLP, and controls, except for carotid-femoral PWV. There were no significant differences among PE groups: women who had experienced HELLP and those with a history of PE without HELLP showed similar rates of RHI ≤ 1.67 (28.6% vs 18.3%, P = 0.254) and RHI ≤ 2.00 (61.2% vs 41.7%, P = 0.055), peripheral AIx@75 ≥ 17% (38.8% vs 30.0%, P = 0.417), aortic AIx@75 ≥ 35% (29.2% vs 20.0%, P = 0.461) and cfPWV × 0.8 > 9.6 m/s, which occurred in only three women, all in the group without previous HELLP (0% vs 5.0%, P = 0.251). On multivariate regression analysis, HELLP syndrome, intrauterine growth restriction (IUGR) and early-onset PE independently predicted endothelial dysfunction at 6 months to 4 years postpartum, after correcting for uterine artery pulsatility index, birth-weight percentile, and maternal blood pressure, age and body mass index. Women with both previous HELLP and early-onset IUGR had a significantly higher prevalence of endothelial dysfunction (P = 0.001). CONCLUSION: Similar vascular abnormalities were found in women previously affected by HELLP syndrome and those with previous PE without HELLP. However, a history of HELLP syndrome, IUGR and early-onset PE seems to identify a subgroup of women with a higher risk for future development of endothelial dysfunction. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Insights into cardiac alterations after pre-eclampsia: an echocardiographic study.

OBJECTIVES: To investigate cardiovascular (CV) performance status several years after early-onset (EO) or late-onset (LO) pre-eclampsia (PE), using echocardiography to assess myocardial strain and left ventricular (LV) torsional mechanics and ventricular-arterial coupling (VAC). METHODS: Thirty non-pregnant women with a previous singleton pregnancy complicated by EO-PE, 30 who had experienced LO-PE and 30 controls underwent echocardiography with two-dimensional (2D) speckle tracking between 6 months and 4 years after delivery and their findings were compared. All women were free from CV risk factors. VAC was defined as the ratio between aortic elastance (Ea) and LV end-systolic elastance (Ees). RESULTS: Women in the EO-PE group showed a persistent subclinical impairment in LV systole and a slight alteration in right ventricular function, with reductions in LV 2D strain (circumferential, radial and longitudinal) and right ventricular 2D strain and impairment of LV torsional mechanics, when compared both with women in the LO-PE group and with healthy controls. Although VAC was within the normal range in the whole study cohort, its individual components Ea and Ees were significantly altered more often in the EO-PE group than in both the LO-PE group and controls. All parameters investigated (except right ventricular 2D strain) were associated independently with gestational age at the time of diagnosis of PE. CONCLUSIONS: Women with a history of EO-PE are more likely to have subclinical impairment of systolic biventricular function than are those with a history of LO-PE and controls. The components of VAC (Ea and Ees) show subclinical alterations which are more significant in women with a history of EO-PE than in those with a history of LO-PE and controls, although VAC itself is maintained. Our study supports the use of closer CV monitoring in previously pre-eclamptic women, particularly those in whom PE was preterm. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Elastic properties of ascending aorta in women with previous pregnancy complicated by early- or late-onset pre-eclampsia.

OBJECTIVES: To evaluate the elastic properties of the ascending aorta in women with a previous pregnancy complicated by early-onset (EO) or late-onset (LO) pre-eclampsia (PE) and the correlation with gestational age (GA), systolic/diastolic blood pressure (SBP/DBP) and mean uterine artery pulsatility index (UtA-PI) at diagnosis of the disease as well as with birth weight of the neonate. METHODS: Thirty women who had a previous pregnancy complicated by EO-PE, 30 with a previous pregnancy complicated by LO-PE and 30 normal controls were selected retrospectively from our electronic database and then recalled for assessment from 6 months to 4 years after delivery. Data regarding GA, SBP/DBP and mean UtA-PI at the diagnosis of PE were obtained from medical records. At our assessment, aortic M-mode and tissue Doppler imaging (TDI) parameters were measured. Aortic diameters were assessed at end-diastole at four levels: Valsalva sinuses, sinotubular junction, tubular tract and aortic arch. Aortic compliance, distensibility, stiffness index (SI), Peterson's elastic modulus (EM), pulse-wave velocity and M-mode strain were calculated using standard formulae. Aortic expansion velocity, early and late diastolic retraction velocities and peak systolic tissue strain (TDI-ϵ) were determined. RESULTS: Aortic diameters at the four levels were significantly greater in both EO-PE and LO-PE groups than in controls. Aortic compliance and distensibility and TDI-ϵ were lower in EO-PE than in LO-PE (P = 0.001, P = 0.002 and P = 0.011, respectively) and controls (P = 0.037, P = 0.044 and P = 0.013, respectively). SI and EM were higher in EO-PE than in LO-PE (P = 0.001 and P < 0.001, respectively) and than in controls (P = 0.035 and P = 0.036, respectively). Multivariate analysis showed GA, DBP and UtA-PI at diagnosis of PE to be independent predictors of aortic elastic properties. CONCLUSIONS: Elastic properties of the ascending aorta were altered in women with a previous pregnancy complicated by EO-PE, but not in those with LO-PE. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Effects of immune system status on long-term results of cardiac resynchronization therapy.

AIM: Cardiac resynchronization therapy (CRT) is an effective therapy for patients with reduced systolic function and enlarged QRS. Recently, some Authors have demonstrated that the presence of positive antinuclear antibodies (ANAs) may play a role in the development of heart failure in a population of patients implanted with PM. METHODS: We investigated the effect of positive ANAs in 90 patients (mean age 71±8 years) implanted with a CRT device in our Centre between May 2010 and June 2013. To assess for immunologic contribution to CRT outcome, patients were divided into positive and negative ANAs (ANA +, ANA -), considering as positive patients with an ANAs dilution > 1:80. The primary endpoint was constituted by a combined endpoint of death or first hospitalization for heart failure; secondary endpoints were constituted by: 1) incidence of first hospitalization for heart failure; and 2) total cause mortality. RESULTS: After a mean follow-up of 1200 days, primary endpoint occurred in 11 patients (30%) of ANA+ group and in 8 patients (15.1%) of ANA-group. The significant difference is due to difference in heart failure events (27% vs. 11.3%, P<0.05), whilst difference in total mortality did not reach statistical significance (10.8% vs. 3.8%). CONCLUSION: Immune status seems to play a role in patients with congestive heart failure. If this immunological alteration is a determinant or a consequence of heart failure remains unclear.

Effects of transcatheter aortic valve implantation on left ventricular mass and global longitudinal strain: tissue Doppler and strain evaluation.

INTRODUCTION: Transcatheter aortic valve implantation is the option of choice for high surgical risk patients suffering from symptomatic aortic stenosis. We aimed to evaluate the influence of baseline global longitudinal strain on left ventricular mass regression after the procedure. METHODS: We enrolled 23 patients with pure symptomatic severe aortic stenosis who underwent CoreValve prosthesis (Medtronic, Minneapolis, MN) implantation. Everyone had echocardiography registration before the procedure and after six months in order to analyze two-, three-, and four-chamber peak longitudinal strain and global longitudinal strain. RESULTS: After the procedure New York Heart Association class, peak and mean aortic valve gradients (p<0.001 for all) improved. Interventricular septum and posterior wall thicknesses decreased (p<0.001 for both). Moreover, left ventricular mass index for body surface area changed from 190±44 to 143±30 g/m(2), (p<0.001). Finally, global longitudinal strain significantly increased (from 9.4±0.9 to 11.5±0.8%; p<0.001), as well as its components. Baseline global longitudinal strain correlated with left ventricular mass regression (r=0.560; p=0.005; 2-sided) and predicted it at linear regression analysis (B=23.707; p=0.005; adjusted R(2)=0.281). CONCLUSIONS: Global longitudinal strain and its components improved six months after the procedure. Moreover, baseline global longitudinal strain seemed to predict left ventricular mass regression in patients with pure aortic stenosis undergoing transcatheter aortic valve implantation. This finding could be related to the extent of myocardial fibrosis which is also responsible for lack of left ventricular mass regression and poorer prognosis.

Elastic aortic properties in hypertrophic cardiomyopathy: a single center echocardiographic evaluation.

OBJECTIVE: Previous studies revealed that hypertrophic cardiomyopathy (HCM) patients have impaired aortic elastic properties with contrasting data about aortic dimensions. We aimed to extend our knowledge about this topic, considering tissue Doppler imaging (TDI) and tissue strain. PATIENTS AND METHODS: 25 HCM patients and 25 healthy volunteers matched for age and sex were enrolled. They underwent transthoracic echocardiography to measure aortic dimensions at four levels (Valsalva sinuses, sinotubular junction, tubular tract, aortic arch), elastic properties (i.e., distensibility, stiffness, M-mode strain, tissue strain), and TDI aortic wall velocities (S', E', A' waves). RESULTS: Aortic dimensions differed between the two groups only at sinotubular junction (18 ± 6 vs. 15 ± 3 mm/m2; p = 0.039) and aortic arch levels (19 ± 5 vs. 11 ± 8 mm/m2; p < 0.001). Aortic stiffness was significantly higher among patients (16.4 ± 23.2 vs. 5.9 ± 3.4; p = 0.034), and TDI waves greater (S': 5.2 ± 1.9 vs. 8.0 ± 2.7 cm/s, p < 0.001; E': -5.3 ± 2.4 vs. -7.2 ± 2.7 cm/s, p = 0.012; A': -5.3 ± 1.6 vs. -8.6 ± 4.5 cm/s, p = 0.002). M-mode and tissue strains, and aortic distensibility did not reach statistical significance, although showing a tendency to altered values in the HCM group. CONCLUSIONS: Patients affected by HCM show a larger aorta and altered aortic elastic properties compared with healthy volunteers. These findings could help to investigate treatment response and prognosis of these alterations.