Sajid Shahul

Cardiac angiogenic imbalance leads to peripartum cardiomyopathy

Peripartum cardiomyopathy (PPCM) is an often fatal disease that affects pregnant women who are near delivery, and it occurs more frequently in women with pre-eclampsia and/or multiple gestation. The aetiology of PPCM, and why it is associated with pre-eclampsia, remain unknown. Here we show that PPCM is associated with a systemic angiogenic imbalance, accentuated by pre-eclampsia. Mice that lack cardiac PGC-1α, a powerful regulator of angiogenesis, develop profound PPCM. Importantly, the PPCM is entirely rescued by pro-angiogenic therapies. In humans, the placenta in late gestation secretes VEGF inhibitors like soluble FLT1 (sFLT1), and this is accentuated by multiple gestation and pre-eclampsia. This anti-angiogenic environment is accompanied by subclinical cardiac dysfunction, the extent of which correlates with circulating levels of sFLT1. Exogenous sFLT1 alone caused diastolic dysfunction in wild-type mice, and profound systolic dysfunction in mice lacking cardiac PGC-1α. Finally, plasma samples from women with PPCM contained abnormally high levels of sFLT1. These data indicate that PPCM is mainly a vascular disease, caused by excess anti-angiogenic signalling in the peripartum period. The data also explain how late pregnancy poses a threat to cardiac homeostasis, and why pre-eclampsia and multiple gestation are important risk factors for the development of PPCM.

Role of breast-feeding in transmission of hepatitis C virus to infants of HCV-infected mothers

BACKGROUND/AIMS The aim of this study was to explore the role of breast-feeding in transmission of hepatitis C virus (HCV) to infants of HCV-infected mothers. METHODS Sixty-five parturient asymptomatic carrier mothers with anti-HCV antibody (index patients) and 42 healthy parturient anti-HCV negative mothers (control subjects) were studied from September 1994 to June 1996. Maternal blood and colostrum were taken from each subject within 5 days post-partum and tested for anti-HCV and HCV RNA. Blood samples were collected from all infants at birth (cord blood) and at 1, 3, 6, 9 and 12 months of age. All infants were breast-fed. By 3 months post-partum, five of 65 index patients developed symptomatic liver disease and three of their infants developed acute viral hepatitis. Genotyping and subsequent nucleotide sequencing of the hepatitis C genome was done on these three symptomatic mother-baby pairs. RESULTS Within 5 days post-partum, the 65 carrier mothers had anti-HCV ranging from 1:40 to 1:30,000 and HCV-RNA ranging from 10(2) to 2.5x10(6) copies/ml. Both anti-HCV antibody and HCV-RNA were present in colostral samples but in significantly lower levels (p<0.0001). The five symptomatic mothers had anti-HCV titers ranging from 1:45,000 to 1:90,000 and HCV-RNA ranging from 2.5x10(8) to 4.5x10(9) copies/ml; three of their infants were symptomatic by 3 months of age. Hepatitis C virus genotype (3a) was concordant within each of the three mother-baby pairs, and all three pairs demonstrated greater than 97% homologies between pairs. These three infants were delivered by elective cesarean section at term, breast-fed regularly and there was no apparent maternal breast nipple trauma. None of the remaining infants had evidence of HCV infection up to 1 year of age. All 42 mother-infant pairs from the control group remained anti-HCV negative throughout this study. CONCLUSION Among asymptomatic mothers breast-feeding seems safe. Symptomatic women, especially with high viral loads, should not breast-feed to avoid the risk of viral transmission through breast-feeding.

Utility of a transesophageal echocardiographic simulator as a teaching tool.

OBJECTIVE This study was designed to test the hypothesis that simulator-based transesophageal echocardiographic training was a more effective method of training anesthesia residents with no prior experience in echocardiography as compared with conventional methods of training (books, articles, and web-based resources). STUDY DESIGN A prospective randomized study. SETTING An academic medical center (teaching hospital). PARTICIPANTS The participants consisted of first-year anesthesia residents. INTERVENTION The study design was composed of 2 groups: a control group (group 1, conventional group) and a study group (group 2, simulator group). The residents belonging to group 2 (simulator group) received a 90-minute simulator-based teaching session moderated by a faculty experienced in transesophageal echocardiography. Residents belonging to group 1 (conventional group) were asked to review the guidelines of the comprehensive intraoperative transesophageal echocardiographic examination published by the American Society of Echocardiography and the Society of Cardiovascular Anesthesiologists. They also were encouraged to use other learning resources (eg, textbooks, electronic media, and web-based resources) to understand the underlying concepts of echocardiography. Written pre- and post-test was administered to both groups. MEASUREMENTS AND MAIN RESULTS The groups were compared for the pretest scores by the nonparametric Mann-Whitney U test. Pre- and post-test scores were compared with a Wilcoxon paired test in the individual groups. The results showed a statistically significant difference between the scores of the 2 groups with better scores in the simulation group in the post-training test. CONCLUSION The simulator-based teaching model for transesophageal echocardiography is a better method of teaching the basic concepts of transesophageal echocardiography like anatomic correlation, structure identification, and image acquisition.

Subclinical Left Ventricular Dysfunction in Preeclamptic Women With Preserved Left Ventricular Ejection Fraction A 2D Speckle-Tracking Imaging Study

Background—Patients with preeclampsia are at risk for cardiovascular disease. Changes in cardiac function are subtle in preeclampsia and are difficult to quantify with conventional imaging. Strain measurements using speckle-tracking echocardiography have been used to sensitively quantify abnormalities in other disease settings. Methods and Results—We evaluated the feasibility and sensitivity of strain imaging using speckle-tracking echocardiography in women with preeclampsia. Forty-seven women were enrolled in this pilot study and 39 were analyzed: 11 with preeclampsia, 17 without a hypertensive disorder, and 11 with nonproteinuric hypertension. Echocardiographic ejection fraction and global peak longitudinal, radial, and circumferential strain were measured. Longitudinal strain was significantly worsened in women with preeclampsia compared with women without a hypertensive disorder (P=0.0001). Similar results were observed for radial strain (P=0.006) and circumferential strain (P=0.03). Women with preeclampsia also had significantly worsened longitudinal (P=0.04), radial (P=0.01), and circumferential (P=0.002) strain compared with women with nonproteinuric hypertension. Women with preeclampsia did not have a significantly different ejection fraction compared with women without a hypertensive disorder (P=0.16) and women with nonproteinuric hypertension (P=0.44). Conclusions—Myocardial strain imaging using speckle tracking is more sensitive than left ventricular ejection fraction to detect differences in left ventricular systolic function in women with and without preeclampsia.

Transthoracic echocardiographic simulator: normal and the abnormal.

Despite anesthesiologists’ use of transesophageal echocardio-graphy (TEE) and familiarity with cardiovascular imaging,TTE has not been as widely used perioperatively. With therecent availability of relatively inexpensive and portable ultra-sound systems, there has been a resurgence of interest in usingthis modality to its full potential. Another possible reason for itsunderutilization could be the lack of structured training programsfor anesthesiologists. The National Board of Echocardiographymandates a minimum of 150 TTE examinations to be per-formed by operators, with 300 interpretations under appropriatesupervision, as requirements for certification. However, a short-age of trained personnel and staffing-related issues are two ofthe reasons for a comprehensive TTE examination either notbeing performed routinely or not in a timely fashion, particu-larly for preoperative risk stratification.TTE is a modality that requires considerable skill in imageacquisition and supervised training for interpretation. Tradi-tionally, cardiologists have employed the services of trainedechocardiography technicians for image acquisition, whereasemergency room and critical care physicians have to acquireand interpret transthoracic images themselves. Major nationalprofessional societies (eg, the American Society of Anesthesi-ologists, the Society of Cardiovascular Anesthesiologists, andthe Society of Critical Care Medicine) have taken the initiativeto educate their members about the benefits and applications ofechocardiography in routine practice. However, currently thereare no formal TTE image-acquisition training opportunitiesavailable for anesthesiologists.As a result, an increasing demand for this clinical skill isfurther exacerbated by a paucity of training opportunities, ne-cessitating the employment of alternate training methods totrain physicians in TTE. Therefore, the use of simulation tech-nology provides a unique opportunity to create a virtual train-ing environment to offset the initial learning curve and shortenthe eventual training duration.

Perioperative Ultrasound Training in Anesthesiology: A Call to Action.

The purpose of this position paper is to define the scope of perioperative ultrasound (US), review the current status of US training practices during anesthesiology residency, and suggest the recommendations for current and future trainees on how to obtain perioperative US proficiency. We define per

Epidemiology and Mechanisms of De Novo and Persistent Hypertension in the Postpartum Period

Background— The pathophysiology of hypertension in the immediate postpartum period is unclear. Methods and Results— We studied 988 consecutive women admitted to a tertiary medical center for cesarean section of a singleton pregnancy. The angiogenic factors soluble fms-like tyrosine kinase 1 and placental growth factor, both biomarkers associated with preeclampsia, were measured on antepartum blood samples. We then performed multivariable analyses to determine factors associated with the risk of developing postpartum hypertension. Of the 988 women, 184 women (18.6%) developed postpartum hypertension. Of the 184 women, 77 developed de novo hypertension in the postpartum period, and the remainder had a hypertensive disorder of pregnancy in the antepartum period. A higher body mass index and history of diabetes mellitus were associated with the development of postpartum hypertension. The antepartum ratio of soluble fms-like tyrosine kinase 1 to placental growth factor positively correlated with blood pressures in the postpartum period (highest postpartum systolic blood pressure [r=0.29, P<0.001] and diastolic blood pressure [r=0.28, P<0.001]). Moreover, the highest tertile of the antepartum ratio of soluble fms-like tyrosine kinase 1 to placental growth factor was independently associated with postpartum hypertension (de novo hypertensive group: odds ratio, 2.25; 95% confidence interval, 1.19–4.25; P=0.01; in the persistent hypertensive group: odds ratio, 2.61; 95% confidence interval, 1.12–6.05; P=0.02) in multivariable analysis. Women developing postpartum hypertension had longer hospitalizations than those who remained normotensive (6.5±3.5 versus 5.7±3.4 days; P<0.001). Conclusions— Hypertension in the postpartum period is relatively common and is associated with prolonged hospitalization. Women with postpartum hypertension have clinical risk factors and an antepartum plasma angiogenic profile similar to those found in women with preeclampsia. These data suggest that women with postpartum hypertension may represent a group of women with subclinical or unresolved preeclampsia.

Detection of Myocardial Dysfunction in Septic Shock: A Speckle-Tracking Echocardiography Study.

BACKGROUND:Patients with septic shock are at increased risk of myocardial dysfunction. However, the left ventricular ejection fraction (EF) typically remains preserved in septic shock. Strain measurement using speckle-tracking echocardiography may quantify abnormalities in myocardial function not detected by conventional echocardiography. To investigate whether septic shock results in greater strain changes than sepsis alone, we evaluated strain in patients with sepsis and septic shock. METHODS:We prospectively identified 35 patients with septic shock and 15 with sepsis. These patients underwent serial transthoracic echocardiograms at enrollment and 24 hours later. Measurements included longitudinal, radial, and circumferential strain in addition to standard echocardiographic assessments of left ventricular function. RESULTS:Longitudinal strain worsened significantly over 24 hours in patients with septic shock (P < 0.0001) but did not change in patients with sepsis alone (P = 0.43). No significant changes in radial or circumferential strain or EF were observed in either group over the 24-hour measurement period. In patients with septic shock, the significant worsening in longitudinal strain persisted after adjustment for left ventricular end-diastolic volume and vasopressor use (P < 0.0001). In patients with sepsis, adjustment for left ventricular end-diastolic volume and vasopressor use did not alter the finding of no significant differences in longitudinal strain (P = 0.48) or EF (P = 0.96). CONCLUSIONS:In patients with septic shock, but not sepsis, myocardial strain imaging using speckle-tracking echocardiography identified myocardial dysfunction in the absence of changes in EF. These data suggest that strain imaging may play a role in cardiovascular assessment during septic shock.

En Face View of the Mitral Valve: Definition and Acquisition

A 3-dimensional echocardiographic view of the mitral valve, called the “en face” or “surgical view,” presents a view of the mitral valve similar to that seen by the surgeon from a left atrial perspective. Although the anatomical landmarks of this view are well defined, no comprehensive echocardiographic definition has been presented. After reviewing the literature, we provide a definition of the left atrial and left ventricular en face views of the mitral valve. Techniques used to acquire this view are also discussed.

Circulating Antiangiogenic Factors and Myocardial Dysfunction in Hypertensive Disorders of Pregnancy

Hypertensive disorders of pregnancy (HDP) are associated with subclinical changes in cardiac function. Although the mechanism underlying this finding is unknown, elevated levels of soluble antiangiogenic proteins such as soluble fms-like tyrosine kinase-1 (sFlt1) and soluble endoglin (sEng) are associated with myocardial dysfunction and may play a role. We hypothesized that these antiangiogenic proteins may contribute to the development of cardiac dysfunction in HDP. We prospectively studied 207 pregnant women with HDP and nonhypertensive controls and evaluated whether changes in global longitudinal strain (GLS) observed on echocardiography is specific for HDP and whether these changes correlate with HDP biomarkers, sFlt1 and sEng. A total of 62 (30%) patients were diagnosed with preeclampsia (group A), 105 (51%) did not have an HDP (group B), and 40 (19%) were diagnosed with chronic or gestational hypertension (group C). Blood was drawn and sFlt1 and sEng levels measured using enzyme-linked immunosorbent assay. Comprehensive echocardiograms, including measurement of GLS, were performed on all patients. Overall, GLS was worse in women in group A (preeclampsia) than those in group B or C. Increasing sFlt1 and sEng levels correlated with worsening GLS (r=0.44 for sFlt1 and r=0.46 for sEng, both P<0.001), which remained significant after multivariable analysis (r=0.18 and r=0.22, both P⩽0.01). Increasing levels also correlated with increasing left ventricular mass index, which also remained significant after multivariable analysis (r=0.20 for sFlt1 and 0.19 for sEng, both P=0.01). Elevated circulating levels of antiangiogenic proteins in HDP correlate with and may contribute to myocardial dysfunction as measured by GLS.