Talk:Cardiovascular System - Heart Rate Development

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Raghunathan S, Islas JF, Mistretta B, Iyer D, Shi L, Gunaratne PH, Ko G, Schwartz RJ & McConnell BK. (2019). Conversion of human cardiac progenitor cells into cardiac pacemaker-like cells. J. Mol. Cell. Cardiol. , 138, 12-22. PMID: 31678351 DOI.

Conversion of human cardiac progenitor cells into cardiac pacemaker-like cells.

Abstract We used a screening strategy to test for reprogramming factors for the conversion of human cardiac progenitor cells (CPCs) into Pacemaker-like cells. Human transcription factors SHOX2, TBX3, TBX5, TBX18, and the channel protein HCN2, were transiently induced as single factors and in trio combinations into CPCs, first transduced with the connexin 30.2 (CX30.2) mCherry reporter. Following screens for reporter CX30.2 mCherry gene activation and FACS enrichment, we observed the definitive expression of many pacemaker specific genes; including, CX30.2, KCNN4, HCN4, HCN3, HCN1, and SCN3b. These findings suggest that the SHOX2, HCN2, and TBX5 (SHT5) combination of transcription factors is a much better candidate in driving the CPCs into Pacemaker-like cells than other combinations and single transcription factors. Additionally, single-cell RNA sequencing of SHT5 mCherry+ cells revealed cellular enrichment of pacemaker specific genes including TBX3, KCNN4, CX30.2, and BMP2, as well as pacemaker specific potassium and calcium channels (KCND2, KCNK2, and CACNB1). In addition, similar to human and mouse sinoatrial node (SAN) studies, we also observed the down-regulation of NKX2.5. Patch-clamp recordings of the converted Pacemaker-like cells exhibited HCN currents demonstrated the functional characteristic of pacemaker cells. These studies will facilitate the development of an optimal Pacemaker-like cell-based therapy within failing hearts through the recovery of SAN dysfunction. Copyright © 2019 Elsevier Ltd. All rights reserved. KEYWORDS: CPCs; HCN; Pacemaker cells; Sinoatrial node; hADMSCs PMID: 31678351 DOI: 10.1016/j.yjmcc.2019.09.015

Non-invasive fetal electrocardiography for the detection of fetal arrhythmias

Prenat Diagn. 2019 Jan 2. doi: 10.1002/pd.5412. [Epub ahead of print]

Behar JA1, Bonnemains L2, Shulgin V3, Oster J4, Ostras O5, Lakhno I6.

Abstract OBJECTIVE: To assess whether non-invasive fetal electrocardiography (NI-FECG) enables the diagnosis of fetal arrhythmias.

METHODS: A total of 500 echocardiography and NI-FECG recordings were collected from pregnant women during a routine medical visit in this multicenter study. All the cases with fetal arrhythmias (n = 12) and a matching number of control (n = 14) were used. Two perinatal cardiologists analyzed the extracted NI-FECG while blinded to the echocardiography. The NI-FECG based diagnosis was compared to the reference fetal echocardiography diagnosis.

RESULTS: NI-FECG and fetal echocardiography agreed on all cases (Ac=100%) on the presence of an arrhythmia or not. However, in one case the type of arrhythmia identified by the NI-FECG was incorrect because of the low resolution of the extracted fetal P-wave which prevented resolving the mechanism (2:1 atrioventricular conduction) of the atrial tachycardia.

CONCLUSION: It is possible to diagnose fetal arrhythmias using the NI-FECG technique. However, this study identifies that improvement in algorithms for reconstructing the P-wave is critical to systematically resolve the mechanisms underlying the arrhythmias. The elaboration of a NI-FECG Holter device will offer new opportunities for fetal diagnosis and remote monitoring of problematic pregnancies because of its low-cost, non-invasiveness, portability and minimal set-up requirements.

This article is protected by copyright. All rights reserved.

PMID: 30602066 DOI: 10.1002/pd.5412


Enhancement of low-quality fetal electrocardiogram based on time-sequenced adaptive filtering

Med Biol Eng Comput. 2018 Jun 25. doi: 10.1007/s11517-018-1862-8. [Epub ahead of print]

Fotiadou E1, van Laar JOEH2, Oei SG2, Vullings R3.


Extraction of a clean fetal electrocardiogram (ECG) from non-invasive abdominal recordings is one of the biggest challenges in fetal monitoring. An ECG allows for the interpretation of the electrical heart activity beyond the heart rate and heart rate variability. However, the low signal quality of the fetal ECG hinders the morphological analysis of its waveform in clinical practice. The time-sequenced adaptive filter has been proposed for performing optimal time-varying filtering of non-stationary signals having a recurring statistical character. In our study, the time-sequenced adaptive filter is applied to enhance the quality of multichannel fetal ECG after the maternal ECG is removed. To improve the performance of the filter in cases of low signal-to-noise ratio (SNR), we enhance the ECG reference signals by averaging consecutive ECG complexes. The performance of the proposed augmented time-sequenced adaptive filter is evaluated in both synthetic and real data from PhysioNet. This evaluation shows that the suggested algorithm clearly outperforms other ECG enhancement methods, in terms of uncovering the ECG waveform, even in cases with very low SNR. With the presented method, quality of the fetal ECG morphology can be enhanced to the extent that the ECG might be fit for use in clinical diagnostics. Graphical abstract The extracted fetal ECG signals from non-invasive abdominal recordings still contain a substantial amount of noise. The time-sequenced adaptive filter provides a relatively accurate estimate of the underlying fetal ECG signal when the quality of the reference channels is enhanced prior to filtering.

KEYWORDS: Electrocardiography; Fetal ECG de-noising; Fetal ECG enhancement; Time-sequenced adaptive filter PMID: 29938302 PMCID: PMC6245004 DOI: 10.1007/s11517-018-1862-8

Fetal Electrocardiogram Enhancement 01.jpg

Computerized analysis of cardiotocograms and ST signals is associated with significant reductions in hypoxic-ischemic encephalopathy and cesarean delivery: an observational study in 38 466 deliveries

Am J Obstet Gynecol. 2018 Dec 27. pii: S0002-9378(18)32288-9. doi: 10.1016/j.ajog.2018.12.037.

Lopes-Pereira J1, Costa A2, Ayres-de-Campos D3, Costa-Santos C4, Amaral J5, Bernardes J2.

Abstract BACKGROUND: Intrapartum cardiotocography (CTG) is widely used in high-resource countries and remains at the centre of fetal monitoring and the decision to intervene, but there is ample evidence of poor reliability in visual interpretation, as well as limited accuracy in identifying fetal hypoxia. Combined monitoring of CTG and ST segment signals was developed to increase specificity, but analysis relies heavily on CTG interpretation and is therefore also affected by the previously referred problems. Computerized analysis was developed to overcome these limitations, aiding in the quantification of parameters that are difficult to evaluate visually, such as variability, integrating the complex guidelines of combined CTG and ST analysis, and using visual and sound alerts to prompt healthcare professionals to re-evaluate features associated with fetal hypoxia.

OBJECTIVE: To evaluate the effect of introducing a central fetal monitoring system with computerized analysis of CTG and ST signals into the labor ward of a tertiary care university hospital where all women are continuously monitored with CTG. The incidence of adverse perinatal outcomes and intervention rates was evaluated over time.

STUDY DESIGN: In this retrospective cohort study, yearly rates of hypoxic-ischemic encephalopathy, instrumental vaginal delivery, overall cesarean delivery, and urgent cesarean delivery were obtained from the hospital's clinical databases. The rates occurring in the period from January 2001 to December 2003, before the introduction of central monitoring system with computerized analysis of CTG and ST signals (Omniview-SisPorto), were compared to those occurring from January 2004 to December 2014, after introduction of the system. All rates were calculated with 95% confidence intervals (95% CI).

RESULTS: A total of 38 466 deliveries occurred during this period. After introduction of the system, there was a significant decrease in the number of hypoxic-ischemic encephalopathy cases per 1000 births (5.3‰, 95%CI=[4.0,7.0] vs. 2.2‰, 95%CI=[1.7,2.8]; RR=0.42, 95%CI=[0.29,0.61]), overall cesarean delivery rates (29.9%, 95%CI=[28.9,30.8] vs. 28.3%, 95%CI=[27.8,28.8]; RR=0.96, 95% CI=[0.92,0.99]), and urgent cesarean deliveries (21.6%, 95%CI=[20.7-22.4] vs. 19.2%, 95%CI=[18.8-19.7]; RR=0.91, 95% CI=[0.87,0.95]). The instrumental vaginal delivery rate increased (19.5%, 95%CI=[18.7-20.3] vs. 21.4%, 95%CI=[21.0-21.9; RR=1.07, 95% CI 1.02-1.13].

CONCLUSION: Introduction of computerized analysis of CTG and ST signals in a tertiary care hospital was associated with a significant reduction in the incidence of hypoxic-ischemic encephalopathy and a modest reduction in cesarean deliveries.

Copyright © 2018. Published by Elsevier Inc.

KEYWORDS: Central monitoring; electronic fetal monitoring; fetal; fetal distress; heart rate; intrapartum surveillance; neonatal acidemia; neonatal asphyxia; neonatal encephalopathy; non-reassuring heart rate tracings; real-time alerts PMID: 30594567 DOI: 10.1016/j.ajog.2018.12.037

Quantile Score: A New Reference System for Quantitative Fetal Echocardiography Based on a Large Multicenter Study

J Am Soc Echocardiogr. 2018 Dec 24. pii: S0894-7317(18)30510-8. doi: 10.1016/j.echo.2018.09.012.

Gu X1, Zhu H2, Zhang Y1, Han J1, Zhang H3, Liu Y4, Wang A5, Liu B6, Xue J7, Sun B8, Weng Z9, Ge S10, He Y11.

Abstract BACKGROUND: Normative ranges of fetal echocardiographic measurements are important for quantitative diagnosis of fetal cardiovascular disease. The current normative ranges were derived from small samples and were based on the hypothesis of a normal distribution of these measurements during fetal cardiovascular growth. The aims of this study were to test the hypothesis of a normal distribution of fetal echocardiographic measurements in a large multicenter cohort and to propose a reference system without the normal distribution hypothesis to improve accuracy of fetal echocardiographic measurements.

METHODS: Fifty-two variables from 6,343 normal fetal echocardiographic examinations were acquired from seven Chinese centers. The hypothesis of a normal distribution used in ordinary least squares regression was tested with the Jarque-Bera test. The quantile score (q score) derived from quantile regression without normal distribution hypothesis was compared with the Z score derived from ordinary least squares regression. A total of 288 fetuses with outflow tract and great artery abnormalities and 300 normal fetuses were used to compare the diagnostic accuracy of q and Z scores.

RESULTS: All fetal echocardiographic measurements showed non-normal distributions (P < .001). The normal range was underestimated by ordinary least squares regression compared with quantile regression by 30 ± 11%. The partial normalized areas under the receiver operating characteristic curve within the 20% false-positive rate were 0.62 and 0.50 for the q and Z scores, respectively.

CONCLUSIONS: The q score provides a more robust system for determining normative ranges of fetal echocardiographic measurements. The improved sensitivity of matched false-positive rates makes the q score a more accurate reference for prenatal diagnosis, assessment, and prognosis of fetal cardiovascular disease.

Copyright © 2018 American Society of Echocardiography. All rights reserved.

KEYWORDS: Fetal echocardiography; Quantile score; Z score PMID: 30591282 DOI: 10.1016/j.echo.2018.09.012

Diurnal rhythm of fetal heart rate in third trimester of pregnancy

Zhonghua Fu Chan Ke Za Zhi. 2018 Dec 25;53(12):849-854. doi: 10.3760/cma.j.issn.0529-567x.2018.12.009.

[Article in Chinese; Abstract available in Chinese from the publisher] Li SF1, Wang Y, Li GF, Zhao YY, Chen L, Zhang S.

Abstract in English, Chinese

Objective: To investigate the diurnal rhythms of fetal heart rate in third trimester of pregnancy. Methods: From June 2014 and October 2017, 97 cases of low-risk pregnancy women who received antenatal care and deliveried in Peking University Third Hospital were collected. Totally 130 cases of fetal heart rate and maternal holter monitoring data were analyzed. All cases were singleton pregnancy, cephalic position and had normal perinatal outcome. They were divided into three groups based on gestational age, 29 cases (22.3%,29/130) in pregnancy 28-33(+6) weeks, 37 cases (28.5%,37/130) in 34-36(+6) weeks, and 64 cases (49.2%, 64/130) in 37-40(+6) weeks. Fetal heart baseline (FHB) , fetal heart baseline variation (FHBV) , fetal heart rate acceleration area and maternal heart rate were acquired by computer, their diurnal rhythms and the differences among three groups were analyzed. Results: FHB、FHBV、fetal heart rate acceleration area and maternal heart rate all presented diurnal rhythms. (1) FHB rose in daytime and decreased at night with the minimum value at 2:00-5:00, and didn't decline further at night with the advancing of gestational age (P=0.548). (2) FHBV was similar to FHB, which rose in daytime and decreased at night, but declined smaller at night with the advancing of gestational age, especially after 37 weeks (P<0.01). (3) Fetal heart rate acceleration area reduced in daytime and enlarged at night, and enlarged more with the advancing of gestational age. (4) The diurnal rhythm of maternal heart rate was consistent with fetal heart rate. FHB lagged behind maternal heart rate for 1-2 hours when declining to the nocturnal nadir but been basically in sync with maternal heart rate when recovered. Conclusion: The basic characteristics of fetal heart rate in normal pregnancy exist obviously diurnal rhythms, and change in different trends with the advancing of gestational age.

KEYWORDS: Circadian rhythm; Heart rate, fetal; Pregnancy trimester, third PMID: 30585024

Early fetal ultrasound screening for major congenital heart defects without Doppler

Eur J Obstet Gynecol Reprod Biol. 2018 Dec 14;233:93-97. doi: 10.1016/j.ejogrb.2018.11.030.

García Fernández S1, Arenas Ramirez J2, Otero Chouza MT2, Rodriguez-Vijande Alonso B2, Llaneza Coto ÁP3.


OBJECTIVE: Congenital heart defects are the most common major structural fetal abnormalities. Color flow mapping has played a dominant role in the detection of abnormalities during the first trimester, regardless of the International Society of Ultrasound in Obstetrics and Gynecology warning on the use of Doppler during early pregnancy. The aim of our study was to investigate the use of transvaginal two-dimensional sonography without Doppler for assessing the four-chamber view and the outflow tract view of fetuses at 11-13 weeks of gestation for cardiac screening of major congenital heart defects.

STUDY DESIGN: This was a prospective observational study conducted in the Fetal Medicine Unit of Cabueñes University Hospital, between May 2014 and August 2015. Only low risk-pregnancies were studied. All ultrasonographic examinations were performed by two experienced sonographers in maternal-fetal medicine. The combination of high-frequency transvaginal (nine MHz) and transabdominal (six MHz) ultrasonography transducers were used. An early cardiac screening was performed in 97% of cases. Statistical analysis was carried out using successive multivariate logistic regression models in order to investigate the effect of crown-rump length and body mass index on the probability of visualizing the four-chamber view and/or the outflow tract view.

RESULTS: 663 low-risk pregnant women were included. Regarding the transvaginal approach, neither the crown-rump length nor the body mass index had a statistically significant relationship on the probability of visualization of the four-chamber view and outflow tract view. For the transabdominal approach, the crown-rump length and the body mass index presented a statistically significant effect on the visualization of the four-chamber view and the outflow tract view. Using the transvaginal approach: the success rate of performing a four-chamber view was 89.4% and 82.4% for the outflow tract view. Using the transabdominal approach: the success rate of performing a four-chamber view was 77.8% and 61.5% for the outflow tract view. Four major congenital heart defects were diagnosed, and the prenatal ultrasonagraphic diagnosis was confirmed for all cases.

CONCLUSIONS: Routine first-trimester ultrasonagraphy without Doppler, when performed by experienced sonographers, can effectively identify major congenital heart defects. Additional multicenter well designed studies should clarify the feasibility of this approach.

Copyright © 2018. Published by Elsevier B.V.

KEYWORDS: Congenital heart defects; Doppler ultrasound; Early fetal ultrasonography; First trimester; Safe ultrasound PMID: 30580230 DOI: 10.1016/j.ejogrb.2018.11.030


Antenatal cardiotocography for fetal assessment

Cochrane Database Syst Rev. 2012 Dec 12;12:CD007863. doi: 10.1002/14651858.CD007863.pub3.

Grivell RM, Alfirevic Z, Gyte GM, Devane D. Source Discipline of Obstetrics and Gynaecology, The University of Adelaide, Women's and Children's Hospital, 72 King William Road, Adelaide, Australia, SA 5006.


BACKGROUND: Cardiotocography (CTG) is a continuous recording of the fetal heart rate obtained via an ultrasound transducer placed on the mother's abdomen. CTG is widely used in pregnancy as a method of assessing fetal well-being, predominantly in pregnancies with increased risk of complications. OBJECTIVES: To assess the effectiveness of antenatal CTG (both traditional and computerised assessments) in improving outcomes for mothers and babies during and after pregnancy. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (9 July 2012) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised and quasi-randomised trials that compared traditional antenatal CTG with no CTG or CTG results concealed; computerised CTG with no CTG or CTG results concealed; and computerised CTG with traditional CTG. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility, quality and extracted data. MAIN RESULTS: Six studies (involving 2105 women) are included. Overall, the included studies were not of high quality, and only two had both adequate randomisation sequence generation and allocation concealment. All studies that were able to be included enrolled only women at increased risk of complications.Comparison of traditional CTG versus no CTG showed no significant difference identified in perinatal mortality (risk ratio (RR) 2.05, 95% confidence interval (CI) 0.95 to 4.42, 2.3% versus 1.1%, four studies, N = 1627) or potentially preventable deaths (RR 2.46, 95% CI 0.96 to 6.30, four studies, N = 1627), though the meta-analysis was underpowered to assess this outcome. Similarly, there was no significant difference identified in caesarean sections (RR 1.06, 95% CI 0.88 to 1.28, 19.7% versus 18.5%, three trials, N = 1279) nor in the secondary outcomes that were assessed.There were no eligible studies that compared computerised CTG with no CTG.Comparison of computerised CTG versus traditional CTG showed a significant reduction in perinatal mortality with computerised CTG (RR 0.20, 95% CI 0.04 to 0.88, two studies, 0.9% versus 4.2%, 469 women). However, there was no significant difference identified in potentially preventable deaths (RR 0.23, 95% CI 0.04 to 1.29, two studies, N = 469), though the meta-analysis was underpowered to assess this outcome. There was no significant difference identified in caesarean sections (RR 0.87, 95% CI 0.61 to 1.24, 63% versus 72%, one study, N = 59) or in secondary outcomes. AUTHORS' CONCLUSIONS: There is no clear evidence that antenatal CTG improves perinatal outcome, but further studies focusing on the use of computerised CTG in specific populations of women with increased risk of complications are warranted.

PMID 23235650

Admission cardiotocography: Its role in predicting foetal outcome in high-risk obstetric patients

Australas Med J. 2012;5(10):522-7. doi: 10.4066/AMJ.2012.1267. Epub 2012 Oct 31.

Rahman H, Renjhen P, Dutta S, Kar S. Source Department of Obstetrics & Gynaecology, Sikkim Manipal Institute of Medical Sciences, Gangtok, India.


BACKGROUND: Routine and continuous electronic monitoring of foetal heart rate (FHR) in labour has become an established obstetric practice in high-risk pregnancies in industrialised countries. However, the same may not be possible in non-industrialised countries where antenatal care is inadequate with a large number of high-risk pregnancies being delivered in crowded settings and inadequate health care provider to patient ratios. AIMS: The objective of this study was to evaluate the predictive value of the admission cardiotocogram (CTG) in detecting foetal hypoxia at the time of admission in labour and to correlate the results of the admission CTG with the perinatal outcome in high-risk obstetric cases. METHOD: This was a prospective observational study conducted in the labour and maternity ward of a hospital in Gangtok, India, during the period 2008 to 2010. The study included high-risk pregnant women, admitted via the emergency or outpatient department with a period of gestation ≥36 weeks, in first stage of labour with foetus in the cephalic presentation. All women were subjected to an admission CTG, which included a 20 minute recording of FHR and uterine contractions. RESULTS: One hundred and sixty patients were recruited. The majority of women were primigravida in the 21-30 years age group. About 42% patients were postdated pregnancy followed by pregnancy-induced hypertension (PIH) (15.6%) and premature rupture of membranes (PROM) (11.3%) as the major risk factors. The admission CTG were 'reactive' in 77%, 'equivocal' in 14.4% and 'ominous' in 8.7% women. Incidence of foetal distress, moderate-thick meconium stained liquor and neonatal intensive care unit (NICU) admission was significantly more frequent among patients with ominous test results compared with equivocal or reactive test results on admission. Incidence of vaginal delivery was more common when the test was reactive. CONCLUSION: The admission CTG appears to be a simple non-invasive test that can serve as a screening tool in 'triaging' foetuses of high-risk obstetric patients in non-industrialised countries with a heavy workload and limited resources.

PMID 23173014


Embryology of the conduction system for the electrophysiologist

Indian Pacing Electrophysiol J. 2010 Aug 15;10(8):329-38.

Mirzoyev S, McLeod CJ, Asirvatham SJ.

Mayo Medical School. Abstract

It is critical for interventional electrophysiologists to thoroughly appreciate the topographic and developmental anatomy of the heart and its conduction system. Not only is understanding cardiac anatomy important to prevent complications from collateral damage and to help guide catheter placement, but developmental anatomy allows a deeper appreciation of the arrhythmogenic substrate. In this article, we briefly review the relevant stages of cardiac development for electrophysiologists. The potential location of normal and abnormal conduction patterns resulting from heterogeneous developmental origin is discussed.

During cardiogenesis, myocytes develop into either contractile or conduction cells. Three models have been proposed by which cardiac cells develop and differentiate [1].

  1. The first model has been traditionally adopted by electrophysiologists and is based on a multiple ring theory. It hypothesizes that during heart chamber development and growth, cells in certain regions of the heart tube do not proliferate as rapidly as cells in genetically predetermined atrial and ventricular regions. As the tubular heart grows, the slower-proliferating myocytes form constrictions or rings around which the heart will fold.
  2. A second recruitment model is based on the idea that the conduction system framework is present in early development and enables recruitment of adjacent myocytes to form further elements of the conduction system.
  3. The third model, the early specification model, postulates that myocytes begin expressing either conduction genes or working (contractile) genes early in the development. Cells expressing conduction system markers slowly proliferate and form components of the conduction system, whereas cells lacking the markers proliferate faster and develop into contractile tissue.

PMID: 20811536


Development of the cardiac conduction system: why are some regions of the heart more arrhythmogenic than others?

Circ Arrhythm Electrophysiol. 2009 Apr;2(2):195-207.

Christoffels VM, Moorman AF.

Heart Failure Research Center, Academic Medical Center, 1105 AZ, Amsterdam, The Netherlands.

PMID: 19808465

Evaluation of the embryonic and foetal heart rate at 6(+0) to 11(+6) weeks of gestation

Hamela-Olkowska A, Wiech K, Jalinik K, Zaryjewski D, Kornatowski L, Dangel J. Ginekol Pol. 2009 Mar;80(3):188-92. Polish. PMID: 19382610

"RESULTS: FHR varied between 47 and 192 bpm (mean 154 +/- 26 bpm). At 6 weeks, mean EHR was 116 +/- 21 bpm, then slowly increased, reaching mean 172 +/- 9 bpm at 10 weeks. At 11 weeks the mean FHR achieved the level of 165 +/- 7 bpm. The difference was statistically significant. The r-correlation ratio between FHR and the gestational week was 0.58. In case of 7 embryos (2.75%) at 6.1 to 8.1 weeks of gestation slow FHR was noted (< 100 bpm). The scan performed 7-10 days later revealed miscarriages in all cases. CONCLUSIONS: EHR and FHR in the first trimester depends on gestational week. It increases since 6 to 9 weeks and decreases after 10 weeks. The highest values of FHR are observed between 9 and 10 weeks of gestation. The risk of early pregnancy loss increases significantly in case of detecting slow FHR. FHR can be checked by M-mode methods using any kind of ultrasound machine."


In the adult heart, the initial electrical impulses are generated in the slow pacemaker sino-atrial (SA) node and then propagated across the atrium. This electrical impulse is delayed at the atrioventricular (AV) boundary through specialized slow conducting AV node cardiomyocytes. After the delay at the AV node, electrical propagation travels rapidly through the fast conduction network comprised of the His-Purkinje system, which coordinates ventricular activation to occur from the apex to the base of the heart. This apex-to-base activation allows for efficient ejection of blood from the ventricles into the outflow tracts (OFTs) at the base of the heart

Valvulogenesis: the moving target

Philos Trans R Soc Lond B Biol Sci. 2007 Aug 29;362(1484):1489-503.

Butcher JT, Markwald RR.

Department of Biomedical Engineering, 270 Olin Hall, Cornell University, Ithaca, NY 14853, USA. Abstract Valvulogenesis is an extremely complex process by which a fragile gelatinous matrix is populated and remodelled during embryonic development into thin fibrous leaflets capable of maintaining unidirectional flow over a lifetime. This process occurs during exposure to constantly changing haemodynamic forces, with a success rate of approximately 99%. Defective valvulogenesis results in impaired cardiac function and lifelong complications. This review integrates what is known about the roles of genetics and mechanics in the development of valves and how changes in either result in impaired morphogenesis. It is hoped that appropriate developmental cues and phenotypic endpoints could help engineers and clinicians in their efforts to regenerate living valve alternatives.

PMID 17569640


Cardiotocogram compared to Doppler investigation of the fetal circulation in the premature growth-retarded fetus: longitudinal observations

Ultrasound Obstet Gynecol. 1997 Mar;9(3):152-61.

Hecher K, Hackelöer BJ. Source Department of Prenatal Diagnosis and Therapy, AK Barmbek, Hamburg, Germany.


It was our objective to compare computerized fetal heart rate analysis with blood flow velocity waveform analysis of the arterial and venous fetal circulation in intrauterine growth retardation. We report five illustrative cases with longitudinal observations of fetal Doppler findings and fetal heart rate between 23 and 32 weeks of gestation. Blood flow waveforms were recorded from the umbilical artery, middle cerebral artery, descending aorta, ductus venosus and inferior vena cava. Fetal heart rate was analyzed by a computer system according to the Dawes-Redman criteria. The time sequence of deterioration is described individually for each fetus. An abrupt increase in pulsatility of ductus venosus waveforms with loss of forward flow velocity during atrial contraction preceded abnormally low short-term variation of fetal heart rate. With advanced gestational age and concomitant maternal disease, we observed severe alterations of flow velocity waveforms within 12 h of normal Doppler measurements, which is in contrast to findings in the second trimester, in which severely abnormal venous waveforms were observed over a period of several weeks before intrauterine death occurred. In a fetus with terminally low short-term variation, normal venous waveforms indicated fetal well-being despite an abnormal cardiotocogram (CTG). We challenge the current concept that the CTG is the best available parameter to determine the optimal time for elective delivery of premature growth-retarded fetuses. Deterioration in ductus venosus blood flow seems to precede an abnormal CTG and thus heralds the need for delivery.

PMID 9165678