Acute fetal cardiovascular adaptation to artificial placenta in sheep model.

OBJECTIVE: To describe the acute cardiovascular adaptation of the fetus after connection to an artificial placenta (AP) in a sheep model, using ultrasound and invasive and non-invasive hemodynamic assessment. METHODS: This was an experimental study of 12 fetal sheep that were transferred to an AP system, consisting of a pumpless circuit with umbilical cord connection, at 109-117 days' gestation. The study was designed to collect in-utero and postcannulation measurements in all the animals. The first six consecutive fetuses were fitted with intravascular catheters and perivascular probes to obtain invasive physiological data, including arterial and venous intravascular pressures and perivascular blood flows, with measurements taken in utero and at 5 and 30 min after cannulation. These experiments were designed with a survival goal of 1-3 h. The second set of six fetuses were not fitted with catheters, and experiments were aimed at 3-24 h of survival. Echocardiographic assessment of cardiac anatomy and function, as well as measurements of blood flow and pre- and postmembrane pressures recorded by circuit sensors in the AP system, were available for most of the fetuses. These data were acquired in utero and at 30 and 180 min after cannulation. RESULTS: Compared with in-utero conditions, the pulsatility index at 30 and 180 min after connection to the AP system was reduced in the umbilical artery (median, 1.36 (interquartile range (IQR), 1.06-1.50) vs 0.38 (IQR, 0.31-0.50) vs 0.36 (IQR, 0.29-0.41); P < 0.001 for extreme timepoints) and the ductus venosus (median, 0.50 (IQR, 0.41-0.67) vs 0.29 (IQR, 0.22-0.33) vs 0.36 (IQR, 0.22-0.41); P = 0.011 for extreme timepoints), whereas umbilical venous peak velocity increased (median, 20 cm/s (IQR, 18-22 cm/s) vs 39 cm/s (IQR, 31-43 cm/s) vs 43 cm/s (IQR, 34-54 cm/s); P < 0.001 for extreme timepoints) and flow became more pulsatile. Intravascular monitoring showed that arterial and venous pressures increased transiently after connection, with median values for mean arterial pressure at baseline, 5 min and 30 min of 43 mmHg (IQR, 35-54 mmHg), 72 mmHg (IQR, 61-77 mmHg) and 58 mmHg (IQR, 50-64 mmHg), respectively (P = 0.02 for baseline vs 5 min). Echocardiography showed a similar transient elevation of fetal heart rate at 30 and 180 min after connection compared with in utero (median, 145 bpm (IQR, 142-156 bpm) vs 188 bpm (IQR, 171-209 bpm) vs 175 bpm (IQR, 165-190 bpm); P = 0.001 for extreme timepoints). Fetal cardiac structure and function were mainly preserved; median values for right fractional area change were 36% (IQR, 34-41%) in utero, 38% (IQR, 30-40%) at 30 min and 37% (IQR, 33-40%) at 180 min (P = 0.807 for extreme timepoints). CONCLUSIONS: Connection to an AP system resulted in a transient fetal hemodynamic response that tended to normalize over hours. In this short-term evaluation, cardiac structure and function were preserved. However, the system resulted in non-physiologically elevated venous pressure and pulsatile flow, which should be corrected to avoid later impairment of cardiac function. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Fetal cardiac filling and ejection time fractions by pulsed-wave Doppler: reference ranges and potential clinical application.

OBJECTIVES: Fetal cardiac function can be evaluated using a variety of parameters. Among these, cardiac cycle time-related parameters, such as filling time fraction (FTF) and ejection time fraction (ETF), are promising but rarely studied. We aimed to report the feasibility and reproducibility of fetal FTF and ETF measurements using pulsed-wave Doppler, to provide reference ranges for fetal FTF and ETF, after evaluating their relationship with heart rate (HR), gestational age (GA) and estimated fetal weight (EFW), and to evaluate their potential clinical utility in selected fetal conditions. METHODS: This study included a low-risk prospective cohort of singleton pregnancies and a high-risk population of fetuses with severe twin-twin transfusion syndrome (TTTS), aortic stenosis (AoS) or aortic coarctation (CoA), from 18 to 41 weeks' gestation. Left ventricular (LV) and right ventricular inflow and outflow pulsed-wave Doppler signals were analyzed, using valve clicks as landmarks. FTF was calculated as: (filling time/cycle time) × 100. ETF was calculated as: (ejection time/cycle time) × 100. Intraclass correlation coefficients (ICC) were used to evaluate the intra- and interobserver reproducibility of FTF and ETF measurements in low-risk fetuses. The relationships of FTF and ETF with HR, GA and EFW were evaluated using multivariate regression analysis. Reference ranges for FTF and ETF were then constructed using the low-risk population. Z-scores of FTF and ETF in the high-risk fetuses were calculated and analyzed. RESULTS: In total, 602 low-risk singleton pregnancies and 54 high-risk fetuses (nine pairs of monochorionic twins with severe TTTS, 16 fetuses with AoS and 20 fetuses with CoA) were included. Adequate Doppler traces for FTF and ETF could be obtained in 95% of low-risk cases. Intraobserver reproducibility was good to excellent (ICC, 0.831-0.905) and interobserver reproducibility was good (ICC, 0.801-0.837) for measurements of all timing parameters analyzed. Multivariate analysis of FTF and ETF in relation to HR, GA and EFW in low-risk fetuses identified HR as the only variable predictive of FTF, while ETF was dependent on both HR and GA. FTF increased with decreasing HR in low-risk fetuses, while ETF showed the opposite behavior, decreasing with decreasing HR. Most recipient twins with severe TTTS showed reduced FTF and preserved ETF. AoS was associated with decreased FTF and increased ETF in the LV, with seemingly different patterns associated with univentricular vs biventricular postnatal outcome. The majority of fetuses with CoA had FTF and ETF within the normal range in both ventricles. CONCLUSIONS: Measurement of FTF and ETF using pulsed-wave Doppler is feasible and reproducible in the fetus. The presented reference ranges account for associations of FTF with HR and of ETF with HR and GA. These time fractions are potentially useful for clinical monitoring of cardiac function in severe TTTS, AoS and other fetal conditions overloading the heart. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Prevalence and pattern of cardiovascular magnetic resonance late gadolinium enhancement in highly trained endurance athletes.

BACKGROUND: Intensive endurance exercise may induce a broad spectrum of right ventricular (RV) adaptation/remodelling patterns. Late gadolinium enhancement (LGE) has also been described in cardiovascular magnetic resonance (CMR) of some endurance athletes and its clinical meaning remains controversial. Our aim was to characterize the features of contrast CMR and the observed patterns of the LGE distribution in a cohort of highly trained endurance athletes. METHODS: Ninety-three highly trained endurance athletes (> 12 h training/week at least during the last 5 years; 36 ± 6 years old; 53% male) and 72 age and gender-matched controls underwent a resting contrast CMR. In a subgroup of 28 athletes, T1 mapping was also performed. RESULTS: High endurance training load was associated with larger bi-ventricular and bi-atrial sizes and a slight reduction of biventricular ejection fraction, as compared to controls in both genders (p < 0.05). Focal LGE was significantly more prevalent in athletes than in healthy subjects (37.6% vs 2.8%; p < 0.001), with a typical pattern in the RV insertion points. In T1 mapping, those athletes who had focal LGE had higher extracellular volume (ECV) at the remote myocardium than those without (27 ± 2.2% vs 25.2 ± 2.1%; p < 0.05). CONCLUSIONS: Highly trained endurance athletes showed a ten-fold increase in the prevalence of focal LGE as compared to control subjects, always confined to the hinge points. Additionally, those athletes with focal LGE demonstrated globally higher myocardial ECV values. This matrix remodelling and potential presence of myocardial fibrosis may be another feature of the athlete's heart, of which the clinical and prognostic significance remains to be determined.

Early cardiac remodeling in aortic coarctation: insights from fetal and neonatal functional and structural assessment.

OBJECTIVES: Coarctation of the aorta (CoA) is associated with left ventricular (LV) dysfunction in neonates and adults. Cardiac structure and function in fetal CoA and cardiac adaptation to early neonatal life have not been described. We aimed to investigate the presence of cardiovascular structural remodeling and dysfunction in fetuses with CoA and their early postnatal cardiac adaptation. METHODS: This was a prospective observational case-control study, conducted between 2011 and 2018 in a single tertiary referral center, of fetuses with CoA and gestational age-matched normal controls. All fetuses/neonates underwent comprehensive echocardiographic evaluation in the third trimester of pregnancy and after birth. Additionally, myocardial microstructure was assessed in one fetal and one neonatal CoA-affected heart specimen, using synchrotron radiation-based X-ray phase-contrast microcomputed tomography and histology, respectively. RESULTS: We included 30 fetuses with CoA and 60 gestational age-matched controls. Of these, 20 CoA neonates and 44 controls were also evaluated postnatally. Fetuses with CoA showed significant left-to-right volume redistribution, with right ventricular (RV) size and output dominance and significant geometry alterations with an abnormally elongated LV, compared with controls (LV midventricular sphericity index (median (interquartile range; IQR), 2.4 (2.0-2.7) vs 1.8 (1.7-2.0); P < 0.001). Biventricular function was preserved and no ventricular hypertrophy was observed. Synchrotron tomography and histological assessment revealed normal myocyte organization in the fetal and neonatal specimens, respectively. Postnatally, the LV in CoA cases showed prompt remodeling, becoming more globular (LV midventricular sphericity index (mean ± SD), 1.5 ± 0.3 in CoA vs 1.8 ± 0.2 in controls; P < 0.001) with preserved systolic and normalized output, but altered diastolic, parameters compared with controls (LV inflow peak velocity in early diastole (mean ± SD), 97.8 ± 14.5 vs 56.5 ± 12.9 cm/s; LV inflow peak velocity in atrial contraction (median (IQR), 70.5 (60.1-84.9) vs 47.0 (43.0-55.0) cm/s; LV peak myocardial velocity in atrial contraction (mean ± SD), 5.1 ± 2.6 vs 6.3 ± 2.2 cm/s; P < 0.05). The neonatal RV showed increased longitudinal function in the presence of a patent arterial duct. CONCLUSIONS: Our results suggest unique fetal cardiac remodeling in CoA, in which the LV stays smaller from the decreased growth stimulus of reduced volume load. Postnatally, the LV is acutely volume-loaded, resulting in an overall geometry change with higher filling velocities and preserved systolic function. These findings improve our understanding of the evolution of CoA from fetal to neonatal life. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Three-dimensional regional bi-ventricular shape remodeling is associated with exercise capacity in endurance athletes.

AIMS: Endurance athletes develop cardiac remodeling to cope with increased cardiac output during exercise. This remodeling is both anatomical and functional and shows large interindividual variability. In this study, we quantify local geometric ventricular remodeling related to long-standing endurance training and assess its relationship with cardiovascular performance during exercise. METHODS: We extracted 3D models of the biventricular shape from end-diastolic cine magnetic resonance images acquired from a cohort of 89 triathlon athletes and 77 healthy sedentary subjects. Additionally, the athletes underwent cardio-pulmonary exercise testing, together with an echocardiographic study at baseline and few minutes after maximal exercise. We used statistical shape analysis to identify regional bi-ventricular shape differences between athletes and non-athletes. RESULTS: The ventricular shape was significantly different between athletes and controls (p < 1e-6). The observed regional remodeling in the right heart was mainly a shift of the right ventricle (RV) volume distribution towards the right ventricular infundibulum, increasing the overall right ventricular volume. In the left heart, there was an increment of left ventricular mass and a dilation of the left ventricle. Within athletes, the amount of such remodeling was independently associated to higher peak oxygen pulse (p < 0.001) and weakly with greater post-exercise RV free wall longitudinal strain (p = 0.03). CONCLUSIONS: We were able to identify specific bi-ventricular regional remodeling induced by long-lasting endurance training. The amount of remodeling was associated with better cardiopulmonary performance during an exercise test.

Postnatal persistence of fetal cardiovascular remodelling associated with assisted reproductive technologies: a cohort study.

OBJECTIVE: To assess the postnatal persistence of fetal cardiovascular remodelling associated with assisted reproductive technologies (ART) in children at 3 years of age. DESIGN: A cohort study of children conceived by ART. SETTING: Maternal-Fetal Medicine Unit, Hospital Clinic Barcelona, Spain. POPULATION SAMPLE: Eighty singleton pregnancies conceived by ART and 80 spontaneously conceived (controls) followed from fetal life up to childhood. METHODS: Cardiovascular evaluation was performed at 3 years of corrected age, including echocardiography, carotid intima-media (cIMT) by ultrasound, and blood pressure. MAIN OUTCOME MEASURES: Postnatal persistence of cardiovascular changes in children conceived by ART. RESULTS: Compared with controls, children conceived by ART showed larger atria (right atrial area: control 4.9 cm2 (0.9) versus ART 5.5 cm2 (0.9), P < 0.001), more globular ventricles (right ventricular sphericity index: control mean 1.8 (SD 0.5) versus ART 1.6 (0.2), P < 0.001), and signs of systolic (tricuspid annular plane systolic excursion: control 18 mm (2) versus ART 16 mm (3), P < 0.001) and diastolic dysfunction (isovolumic relaxation time: control 68 ms (12) versus ART 79 ms (12), P < 0.001). ART children also presented increased systolic blood pressure (control 90 mmHg (6) versus ART 94 mmHg (5), P < 0.003) and cIMT (control 0.52 µm (0.14) versus ART 0.60 µm (0.16), P < 0.001) as compared with those spontaneously conceived. CONCLUSIONS: Cardiovascular changes previously reported in ART fetuses persist postnatally at 3 years of age. These results underscore the importance of future studies for assessing the long-term cardiovascular health associated with ART. TWEETABLE ABSTRACT: Cardiovascular changes described in fetuses conceived by ART, persist in children at 3 years of age.

Fetal cardiac remodeling in twin pregnancy conceived by assisted reproductive technology.

OBJECTIVE: Recent data suggest that singleton fetuses conceived by assisted reproductive technology (ART) present cardiovascular remodeling that may persist postnatally. Twin pregnancies are more frequent in the ART population and are associated with increased adverse perinatal outcomes, such as hypertensive disorders, gestational diabetes and preterm birth. However, it is unknown whether cardiac remodeling is also present in twin pregnancies conceived by ART. Our aim was to assess the presence of fetal cardiac remodeling and dysfunction in twin pregnancies conceived by ART as compared with those conceived spontaneously (SC). METHODS: This was a prospective cohort study including 50 dichorionic twin fetuses conceived by ART and 50 SC twin fetuses. The study protocol included collection of baseline/perinatal data and a fetal ultrasound examination at 28-30 weeks' gestation, including assessment of estimated fetal weight, fetoplacental Doppler and fetal echocardiography. Measurements of atrial area, atrial/heart ratio, ventricular sphericity index, free wall thickness, mitral and tricuspid annular plane systolic excursions, and systolic and early diastolic peak velocities were assessed. Multilevel analyses were used to compare perinatal and ultrasonographic parameters. Comparisons of echocardiographic variables were adjusted for parental age, paternal body mass index and incidence of pre-eclampsia. RESULTS: Compared with SC twins, ART twin fetuses showed significant cardiac changes, predominantly affecting the right heart, such as dilated atria (right atrial/heart area: 15.7 ± 3.1 vs 18.4 ± 3.2, P < 0.001), more globular ventricles (right ventricular sphericity index: 1.57 ± 0.25 vs 1.41 ± 0.23, P = 0.001) and thicker myocardial walls (septal wall thickness: 2.57 ± 0.45 mm vs 2.84 ± 0.41 mm, P = 0.034) together with reduced longitudinal motion (tricuspid annular plane systolic excursion: 6.36 ± 0.89 mm vs 5.18 ± 0.93 mm, P < 0.001). CONCLUSIONS: ART twin fetuses present signs of cardiac remodeling and dysfunction. These changes are similar to those observed in ART singletons and reinforce the concept of fetal cardiac programing in ART. These results open opportunities for early detection and intervention in infants conceived by ART. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Differential effect of assisted reproductive technology and small-for-gestational age on fetal cardiac remodeling.

OBJECTIVE: Fetuses conceived by assisted reproductive technology (ART) and those that are small-for-gestational age (SGA) show cardiovascular remodeling in utero; however, these two conditions are often associated. We aimed to evaluate the differential effect of ART and SGA on fetal cardiac remodeling. METHODS: This was a prospective cohort study of term singleton pregnancies seen at our department between April 2011 and September 2013. The cohort was divided according to fetal growth and mode of conception into the following four groups: 102 appropriate-for-gestational-age (AGA) fetuses conceived spontaneously (controls), 72 AGA fetuses conceived by ART (ART-AGA), 31 SGA fetuses conceived by ART (ART-SGA) and 28 SGA fetuses conceived naturally (Spont-SGA). SGA was defined as birth weight < 10th centile. Fetal echocardiography was performed at 28-32 weeks to assess cardiac dimensions, geometry and function. RESULTS: ART fetuses had dilated atria (mean left atrium-to-heart area ratio: controls, 15 ± 2.7%; ART-AGA, 18 ± 4.1%; Spont-SGA, 14 ± 3.7%) and more globular ventricles (left ventricular sphericity index: controls, 1.77 ± 0.2; ART-AGA, 1.68 ± 0.2; Spont-SGA, 1.72 ± 0.2), with normally sized hearts. In contrast, SGA fetuses had enlarged hearts (cardiothoracic ratio: controls, 24 ± 3%; ART-AGA, 24 ± 4%; Spont-SGA, 29 ± 6%), preserved atrial size, more globular and concentric hypertrophic ventricles (left ventricle relative wall thickness: controls, 0.48 ± 0.17; ART-AGA, 0.54 ± 0.13; Spont-SGA, 0.63 ± 0.23). Both ART and SGA fetuses had decreased longitudinal motion (tricuspid annular ring displacement: controls, 6.5 ± 0.8 mm; ART-AGA, 5.5 ± 0.7 mm; Spont-SGA, 5.9 ± 0.6 mm) and impaired relaxation (left isovolumetric relaxation time: controls, 47.0 ± 7.3 ms; ART-AGA, 50.0 ± 7.9 ms; Spont-SGA, 49.5 ± 9.3 ms). ART-SGA fetuses presented a combination of features from both ART and SGA groups. CONCLUSION: SGA and conception with ART were associated with distinct patterns of fetal cardiac remodeling, supporting the concept that they are independent causes of cardiac programming. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Descriptive analysis of different phenotypes of cardiac remodeling in fetal growth restriction.

OBJECTIVE: To identify different cardiac phenotypes among cases of fetal growth restriction (FGR). METHODS: Echocardiography was performed in 126 cases with FGR (birth weight < 10th centile) and 64 appropriate-for-gestational-age (AGA) fetuses. Principal component and cluster analyses were performed to identify different cardiac phenotypes among FGR cases. RESULTS: Three different cardiac phenotypes were identified among the FGR group: globular in 54% of cases, elongated in 29% of cases and hypertrophic in 17% of cases. Those with a globular heart had the lowest median left-ventricular sphericity index (controls, 1.78 (interquartile range (IQR), 1.62-1.97); FGR elongated, 1.92 (IQR, 1.78-2.09); FGR globular, 1.44 (IQR, 1.36-1.52); FGR hypertrophic, 1.65 (IQR, 1.42-1.77); P = 0.001). FGR cases with an elongated left ventricle had nearly normal cardiac dimensions. FGR cases with a hypertrophic phenotype had the highest median left-ventricular wall thickness (controls, 1.22 (IQR, 1.10-1.67) mm/kg; FGR elongated, 1.52 (IQR, 1.28-1.86) mm/kg; FGR globular, 1.65 (IQR, 1.39-1.99) mm/kg; FGR hypertrophic, 3.68 (IQR, 3.45-4.71) mm/kg; P = 0.001) and cardiac dimensions. Globular and elongated phenotypes showed a fetoplacental profile of late-onset FGR, while the hypertrophic phenotype showed signs of early-onset FGR. The hypertrophic group also had the poorest perinatal results, having the lowest birth-weight centile, gestational age at delivery and Apgar score and the highest postnatal blood pressure and aorta intima-media thickness. CONCLUSIONS: FGR induces at least three different cardiac phenotypes, with early-onset FGR cases being associated with a hypertrophic response and worse perinatal outcomes. This cardiac phenotypic classification may improve identification of FGR cases with the highest perinatal and long-term cardiovascular risks. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Fetal cardiovascular remodeling persists at 6 months in infants with intrauterine growth restriction.

OBJECTIVES: Intrauterine growth restriction is associated with increased cardiovascular risk later in life but the link between fetal disease and postnatal risk is not well-documented. We evaluated longitudinally the association between cardiovascular remodeling in small-for-gestational-age (SGA) fetuses and at 6 months of age. METHODS: A cohort of 80 SGA fetuses (defined by estimated fetal and birth weights < 10(th) centile) delivered > 34 weeks' gestation was compared with 80 normally grown age-matched control fetuses, with follow-up at 6 months of corrected age (i.e. 6 months from estimated date of delivery according to first-trimester crown-rump length). Cardiovascular evaluation included a comprehensive echocardiographic assessment in both fetuses and infants and blood pressure and aortic intima-media thickness (aIMT) measurement in infants. Parameters were adjusted by linear regression analysis for gender, gestational age at delivery, pre-eclampsia, prenatal glucocorticoid exposure, Cesarean delivery, admission to neonatal intensive care unit and body surface area. RESULTS: Both pre- and postnatally, when compared with controls, the SGA group showed a more globular cardiac shape (left sphericity index: controls 2.06 vs SGA 1.87 (P = 0.022) prenatally and 1.92 vs 1.67 (P = 0.007) postnatally), as well as signs of systolic longitudinal dysfunction (systolic annular peak velocity (S'): 7.2 vs 6.3 cm/s (P = 0.003) prenatally and 7.9 vs 6.4 cm/s (P < 0.001) postnatally; tricuspid annular plane systolic excursion: 7.2 vs 6.8 mm (P = 0.015) prenatally and 16.0 vs 14.2 mm (P < 0.001) postnatally) and diastolic dysfunction (left isovolumetric relaxation time: 46 vs 52 ms (P < 0.001) prenatally and 50 vs 57 ms (P = 0.034) postnatally). In addition, infants in the SGA group had increased mean blood pressure (mean: 61 vs 70 mmHg, P < 0.001) and maximum aIMT (0.57 vs 0.66 mm; P < 0.001). CONCLUSIONS: Primary cardiovascular changes are already present in the SGA fetus and persist at 6 months of age. These data support prenatal cardiovascular remodeling as a mechanistic pathway of increased risk later in life in cases of SGA, regardless of Doppler abnormalities. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Differential atrial performance at rest and exercise in athletes: Potential trigger for developing atrial dysfunction?

Highly trained athletes show an increased risk of atrial arrhythmias. Little is known about atrial volumes and function during exercise in this population. Our aim was to analyze atrial size and contractile function during exercise. Fifty endurance athletes with 11 ± 8 h of training per week and 30 sedentary control subjects were included. Echocardiography was performed at baseline and during exercise. Left (LA) and right atrial (RA) size and function were assessed by two-dimensional echocardiography. Peak negative strain (Sa) during atrial contraction and active atrial emptying volume (AEV) were measured. Athletes and control subjects showed a significant increment of deformation and AEV of both atria with exercise (P < 0.01 vs baseline for LA and RA). Among athletes, a subgroup with significant LA (n = 8)/RA (n = 15) dilatation (≥40 mL/m2 ) showed a significantly lower increment in AEV with exercise (LA∆AEV: 1.4 ± 1.1 mL/m2 vs 2.1 ± 0.9 mL/m2 , P = 0.04; RA∆AEV: 0.9 ± 0.8 mL/m2 vs 2.3 ± 1.1 mL/m2 , P < 0.01) and lower increment in deformation vs other athletes (LA∆Sa: -3.2 ± 2.9% vs -9.5 ± 4.4%, P < 0.01; RA∆Sa: -2.5 ± 3.3% vs. -9.8 ± 3.3%, P < 0.01). During exercise, active atrial strain increases, but less in athletes compared to controls, but due to larger atrial volumes, they reached similar increases in atrial emptying volume. However, this overall lesser deformation increases from a subgroup with significant atrial dilatation showing impairment in atrial contractile reserve.

Maternal subclinical vascular changes in fetal growth restriction with and without pre-eclampsia.

OBJECTIVE: To assess maternal vascular structure and function in pregnancies complicated by fetal growth restriction (FGR), in women with and without pre-eclampsia (PE) at the time of FGR diagnosis. METHODS: We evaluated 124 women with a pregnancy complicated by FGR, of whom 60 had PE and 64 did not, and compared these findings to those of 110 normal women (controls). The group of FGR pregnancies without PE was further subdivided according to gestational age at FGR diagnosis into early onset (< 32 weeks) or late onset (≥ 32 weeks). Maternal carotid intima-media thickness (IMT), blood pressure (BP), carotid artery distensibility (CD), circumferential wall stress (CWS) and inferior vena cava (IVC) collapsibility were assessed by ultrasound at the time of FGR diagnosis. RESULTS: Compared to controls, cases of FGR with PE showed increased maternal carotid IMT (0.425 (interquartile range (IQR), 0.381-0.486) vs 0.409 (IQR, 0.386-0.439) mm; P = 0.021), BP (mean, 109 (IQR, 101-117) vs 82 (IQR, 77-89) mmHg; P < 0.001) and CWS (19.7 (IQR, 17.0-22.7) vs 12.2 (IQR, 11.1-13.7) kPa; P < 0.001), and reduced CD (25.3 (IQR, 15.7-35.6) vs 31.9 (IQR, 25.4-41.1) kPa(-1) × 10(-3) ; P = 0.037) and IVC collapsibility indices (0.07 (IQR, 0.06-1.11) vs 0.10 (IQR, 0.06-0.13); P = 0.136). Similarly, compared to controls, in cases of FGR without PE maternal carotid IMT (0.436 (IQR, 0.392-0.476) mm; P = 0.001) and BP (88 (IQR, 81-95) mmHg; P < 0.001) were increased but CD and IVC collapsibility were similar. When analysis was subclassified according to gestational age at diagnosis, IMT and CWS were significantly increased only in early-onset FGR while BP was increased in both groups. CONCLUSION: Normotensive women with pregnancy complicated by FGR share some subclinical vascular features with those of women with PE, which further reinforces the notion that, at least in a proportion of cases, there is a common placental disease that influences maternal cardiovascular features.

Septal flash predicts cardiac resynchronization therapy response in patients with permanent atrial fibrillation.

AIMS: Patients with heart failure (HF) as well as atrial fibrillation (AF) have suboptimal response to cardiac resynchronization therapy (CRT). Identification of mechanical abnormalities, amenable to correction with CRT, might improve the selection of candidates and CRT efficiency. We evaluated whether abnormal septal motion, assessed by the presence of septal flash (SF) is related to CRT response in patients with AF. METHODS AND RESULTS: Ninety-four CRT patients with AF were included. Echocardiography was performed in all subjects at baseline and at 12-month follow-up. Abnormal septal motion was defined by the presence of SF (early septal inward/outward motion within the isovolumic contraction period/QRS duration). Response to CRT was defined as a reduction (>15%) of the end-systolic volume of the left ventricle (LV). Univariate and multivariate analyses were performed to identify the predictors of CRT response. The mean age was 69 ± 8 years, 79% were males, and 59% of patients responded to CRT. Cardiovascular death was 14.4% and all-cause mortality was 16.5% during follow-up. Patients with SF at baseline that was acutely corrected by CRT were significantly more likely to respond than patients without SF. Baseline SF was an independent predictor of CRT response (OR 5.24; 95% CI 1.95-14.11). CONCLUSION: Abnormal septal motion, assessed by the presence of SF, is a mechanism amenable to CRT correction. Its correction is associated with a higher likelihood of CRT response in HF patients with long-standing AF. This could improve the selection of candidates to CRT in a subgroup with particularly poor response and long-term prognosis.

Aortic and carotid intima-media thickness in term small-for-gestational-age newborns and relationship with prenatal signs of severity.

OBJECTIVE: To assess carotid and aortic intima-media thickness (IMT) in term small-for-gestational-age (SGA) newborns with and without prenatal signs of severity. METHODS: This prospective study comprised 67 cases diagnosed prenatally and 134 normally grown newborns. Cases were subclassified into SGA with no signs of severity and those with signs of severity, defined as a birth weight below the 3(rd) percentile or abnormal uterine artery Doppler or cerebroplacental ratio. Blood pressure and vascular IMT were evaluated. RESULTS: SGA newborns showed a non-significant trend for higher values of blood pressure. IMT values were significantly increased in SGA newborns, with and without signs of severity, compared with controls. The magnitude of the increase was higher in SGA newborns with signs of severity. CONCLUSIONS: Vascular IMT was increased in SGA newborns, irrespective of the presence or absence of prenatal signs of severity. This finding challenges the notion of 'constitutionally small' SGA, and supports the premise that the majority of SGA newborns have true growth restriction and suffer fetal cardiovascular programming.

Value of annular M-mode displacement vs tissue Doppler velocities to assess cardiac function in intrauterine growth restriction.

OBJECTIVE: To compare the ability of two different methods for longitudinal annular motion measurement, M-mode and tissue Doppler imaging (TDI), to demonstrate cardiac dysfunction in intrauterine-growth-restricted (IUGR) fetuses. METHODS: Cardiac longitudinal annular motion in the basal free wall of the left ventricle (mitral annulus), interventricular septum and tricuspid annulus was assessed in 23 early-onset IUGR cases and 43 controls by TDI (annular peak velocities) and M-mode (displacement). RESULTS: All annular parameters were significantly decreased in the IUGR group with respect to controls using both methods. M-mode showed a trend towards equal performance as classifier between cases and controls, as compared to TDI, mainly in the tricuspid annulus. CONCLUSIONS: Both M-mode and TDI demonstrate annular motion changes and consequently cardiac dysfunction in IUGR fetuses. M-mode imaging is simpler to perform and could be as sensitive as TDI for detecting subtle changes.

Myocardial motion and deformation: What does it tell us and how does it relate to function?

The assessment of cardiac pump function and the potential of local myocardium to contribute to the overall performance are of great importance in many cardiovascular abnormalities. Assessing intrinsic cardiac function requires obtaining information on the true contractility of the heart muscle, assessed locally but interpreted in the context of its contribution to the global ejection performance and potential to adapt to changing circumstances. Contemporary imaging techniques offer the possibility of noninvasive quantification of myocardial deformation. These new clinical tools are attractive to use for the assessment of ventricular function. However, it is of great importance to understand cardiac mechanics - a complex interplay between the tissue structure/shape, force development, and interaction with the environment/neighbors - to interpret alterations in deformation and to extract clinically relevant conclusions. The combination of insight into the measurement techniques and their limitations, together with knowledge of myocardial mechanics and physiology, opens new perspectives to improve the assessment and management of fetal, pediatric, and adult patients.

Realistic simulation of cardiac magnetic resonance studies modeling anatomical variability, trabeculae, and papillary muscles.

Simulated magnetic resonance imaging brain studies have been generated for over a decade. Despite their useful potential, simulated cardiac studies are only emerging. This article focuses on the realistic simulation of cardiac magnetic resonance imaging datasets. The methodology is based on the XCAT phantom, which is modified to increase realism of the simulated images. Modifications include the modeling of trabeculae and papillary muscles based on clinical measurements and published data. To develop and evaluate our approach, the clinical database included 40 patients for anatomical measurements, 10 patients for papillary muscle modeling, and 10 patients for local gray value statistics. The virtual database consisted of 40 digital voxel phantoms. Histograms from different tissues were obtained from the real datasets and compared with histograms of the simulated datasets with the Chi-square dissimilarity metric (χ(2)) and Kullback-Leibler divergence. For the original phantom, χ(2) values averaged 0.65 ± 0.06 and Kullboek-Leibler values averaged 0.69 ± 0.38. For the modified phantom, χ(2) values averaged 0.34 ± 0.12 and Kullboek-Leibler values averaged 0.32 ± 0.15. The proposed approach demonstrated a noticeable improvement of the local appearance of the simulated images with respect to the ones obtained originally.

Noninvasive quantification of the contractile reserve of stunned myocardium by ultrasonic strain rate and strain.

BACKGROUND: We sought to investigate ultrasonic strain rate and strain as new indices to quantify the contractile reserve of stunned myocardium during dobutamine infusion. METHODS AND RESULTS: Stunning of the left ventricular posterior wall was induced in 9 closed-chest pigs after 30 minutes of severe hypoperfusion followed by 60 minutes of reperfusion of the left circumflex coronary artery territory. A second group of 7 animals had no coronary occlusion and served as normal controls. An incremental dobutamine infusion protocol was used in both groups. Changes in regional radial function were monitored by use of ultrasound-derived maximal systolic radial strain rate (SR) and systolic strain (epsilon). In the control group, dobutamine induced an increase in both SR and maximal dP/dt, which correlated linearly (r=0.85). Conversely, epsilon values increased at low doses of dobutamine (2.5 to 5 microg. kg(-1). min(-1)) but decreased during higher infusion rates (10 to 20 microg. kg(-1). min(-1)). During circumflex hypoperfusion, SR and epsilon of the posterior wall decreased from 5.0+/-0.3 s(-1) and 63+/-6% to 2.9+/-0.3 s(-1) and 27+/-4%, respectively (P<0.01). After 60 minutes of reperfusion, SR and epsilon failed to fully resume because of stunning, averaging 3.6+/-0.2 s(-1) and 35+/-3%, respectively (P=0.12 versus ischemia, P<0.05 versus baseline). During dobutamine infusion, SR increased at 5 microg. kg(-1). min(-1) and exceeded baseline values at 20 microg. kg(-1). min(-1) (P<0.05), whereas epsilon increased only at high doses and remained below baseline levels (P<0.05). CONCLUSIONS: The changes in regional function of stunned myocardium during inotropic stimulation could be characterized by use of ultrasonic deformation parameters. During dobutamine infusion, strain-rate values quantified the contractile reserve better than strain values.

Dobutamine stress echocardiography after heart transplantation.

Dobutamine stress echocardiography was performed in 28 heart transplant recipients to study its value in the detection and staging of transplant vasculopathy. Fourteen patients had angiographic evidence of coronary artery disease (group 1), and 14 had angiographically normal coronary arteries (group 2). The dobutamine stress protocol called for a dose increase of dobutamine every 3 minutes until the age-predicted maximal heart rate was achieved. In groups 1 and 2, the mean maximal dose of dobutamine was, respectively, 24 +/- 9 micrograms/kg min and 29 +/- 8 micrograms/kg min, and the mean rate-pressure product was, respectively, 12386 +/- 1777 mm Hg/min and 10753 +/- 1085 mm Hg/min at rest, increasing to 20987 +/- 4020 mm Hg/min and 19795 +/- 2728 mm Hg/min at maximal dose. No patient in group 1 or 2 had deterioration of global or regional wall motion under dobutamine stress. In group 1, seven patients had wall motion abnormalities at rest, normalizing in five of them under dobutamine stress. In group 2, four patients had wall motion abnormalities at rest, normalizing in all patients under dobutamine stress. Consequently, this protocol of dobutamine stress echocardiography is unsuitable for the early detection of transplant vasculopathy despite its proven value in the general population. Conversely, these data suggest that the functional sequelae of transplant vasculopathy are not necessarily prominent, despite the known angiographic underestimation of the extent of the disease.

Quantification of the spectrum of changes in regional myocardial function during acute ischemia in closed chest pigs: an ultrasonic strain rate and strain study.

The objectives of this study were to define the spectrum of regional myocardial function changes during acute ischemia in closed chest animals by using newly developed ultrasonic strain rate and strain indexes derived from regional color Doppler myocardial imaging (CDMI) velocity data. Myocardial ischemia was induced in 18 pigs either with acute total 20-second occlusions (group 1, n = 12) or graded hypoperfusion (40 to 0 mL/min, group 2, n = 6) of the circumflex coronary artery. In addition, a dobutamine challenge (5 to 10 microg/kg per minute) was performed during sustained subtotal ischemia (10 mL/min) in group 2. CDMI acquisitions with parasternal views monitored the myocardial posterior wall function. Regional radial strain rate and strain (epsilon(r)) were measured for systole, isovolumic relaxation, early diastole, and atrial filling, respectively. During total and graded ischemia, epsilon(r) profiles were consistently modified, showing a delayed onset and a decrease in regional systolic thickening as well as increased postsystolic thickening. Radial strain rate and epsilon(r) indexes decreased consistently during systole and early diastole and increased during isovolumic relaxation. End-systolic epsilon(r) could differentiate total ischemia from severe hypoperfusion (10 mL/min), decreasing from 32% +/- 8% to 16% +/- 5% (versus 60% +/- 10% at baseline). During dobutamine infusion (10 microg/kg per minute), end-systolic epsilon(r) tended to decrease from 27% +/- 5% to 18% +/- 11%, whereas postsystolic thickening increased by 2-fold (P <.05). The combined analysis of regional deformation characteristics and global cardiac event timing derived from CDMI data can identify and quantify regional function changes induced by experimental acute ischemia in closed chest pigs. This would appear to be a potentially promising new noninvasive approach to the clinical evaluation of ischemia-induced changes in segmental myocardial function.