DIFFICULTIES IN EVALUATING SYSTOLIC MURMURS IN CHILDREN—With Special Reference to the Functional Systolic Murmur

As a guide in distinguishing between organic and functional systolic murmurs, five characteristics of a murmur should always be noted, namely, (a) the location of maximal intensity of the murmur; (b) the intensity of the murmur itself; (c) the character of the murmur, that is, whether it is blowing, rumbling, rough or harsh; (d) the transmission of the murmur; and (e) the duration of the murmur and its time within the cardiac cycle.Functional systolic murmurs may be found at any of the “valve areas,” are usually faint to moderately loud, are usually soft and blowing in quality, are usually only slightly transmitted, and are usually not heard immediately following the first heart sound.In doubtful cases, those in which history and physical examination alone are not sufficient to make a diagnosis of functional systolic murmur, further studies should be undertaken to determine the presence or absence of organic heart disease.Until a diagnosis of organic heart disease can be made with reasonable certainty, there should be no restriction of activity imposed, because of the likelihood of the development of cardiac neurosis in the patient.     

Difficulties in evaluating systolic murmurs in children; with special reference to the functional systolic murmur

As a guide in distinguishing between organic and functional systolic murmurs, five characteristics of a murmur should always be noted, namely, (a) the location of maximal intensity of the murmur; (b) the intensity of the murmur itself; (c) the character of the murmur, that is, whether it is blowing, rumbling, rough or harsh; (d) the transmission of the murmur; and (e) the duration of the murmur and its time within the cardiac cycle. Functional systolic murmurs may be found at any of the "valve areas," are usually faint to moderately loud, are usually soft and blowing in quality, are usually only slightly transmitted, and are usually not heard immediately following the first heart sound. In doubtful cases, those in which history and physical examination alone are not sufficient to make a diagnosis of functional systolic murmur, further studies should be undertaken to determine the presence or absence of organic heart disease. Until a diagnosis of organic heart disease can be made with reasonable certainty, there should be no restriction of activity imposed, because of the likelihood of the development of cardiac neurosis in the patient.     

Maternal inflammation, growth retardation, and preterm birth: insights into adult cardiovascular disease

The "fetal origin of adult disease Hypothesis" originally described by Barker et al. identified the relationship between impaired in utero growth and adult cardiovascular disease risk and death. Since then, numerous clinical and experimental studies have confirmed that early developmental influences can lead to cardiovascular, pulmonary, metabolic, and psychological diseases during adulthood with and without alterations in birth weight. This so called "fetal programming" includes developmental disruption, immediate adaptation, or predictive adaptation and can lead to epigenetic changes affecting a specific organ or overall health. The intrauterine environment is dramatically impacted by the overall maternal health. Both premature birth or low birth weight can result from a variety of maternal conditions including undernutrition or dysnutrition, metabolic diseases, chronic maternal stresses induced by infections and inflammation, as well as hypercholesterolemia and smoking. Numerous animal studies have supported the importance of both maternal health and maternal environment on the long term outcomes of the offspring. With increasing rates of obesity and diabetes and survival of preterm infants born at early gestational ages, the need to elucidate mechanisms responsible for programming of adult cardiovascular disease is essential for the treatment of upcoming generations.     

Age-related patterns of reproductive success among female mountain gorillas

A key goal of life history theory is to explain the effects of age and parity on the reproductive success of iteroparous organisms. Age-related patterns may be influenced by changes in maternal experience or physical condition, and they may reflect maternal investment trade-offs between current versus future reproduction. This article examines the influences of age and parity upon the interbirth intervals (IBI), offspring survival, and birth rates of 66 female mountain gorillas in the Virunga Volcano region from 1967-2004. Fertility was relatively low for females below age 12; improved as they matured; and then declined as they aged further. Primiparous mothers had 50% higher offspring mortality and 20% longer IBI than second-time mothers, though only the difference with IBI was statistically significant. The length of subsequent IBI was positively correlated with birth order but not with the mother's age. Mountain gorillas showed no evidence of an extended postreproductive lifespan. Age-related patterns seem most likely to reflect changes in the physical condition of the mother, but more detailed studies are needed to quantify those physical differences, and to obtain behavioral evidence that would provide more direct measures of maternal investment and experience.     

Neck and shoulder pain

Neck and shoulder pains are presenting or incidental symptoms in a large variety of conditions. There may be similarities in the anatomicophysiological mechanism of pain production and in the clinical picture in many of these conditions. Many of the vague and refractory cases of neck and shoulder pain and of migraine may be due to cervical disc disease. Scalenus anticus syndrome and cardiac disease can be diagnosed or differentiated from cervical disc syndrome only by thorough investigation. Proper treatment of neck and shoulder pain is dependent upon correct diagnosis through complete history, physical examination and laboratory tests, as described in this presentation.     

NECK AND SHOULDER PAIN

Neck and shoulder pains are presenting or incidental symptoms in a large variety of conditions.There may be similarities in the anatomicophysiological mechanism of pain production and in the clinical picture in many of these conditions.Many of the vague and refractory cases of neck and shoulder pain and of migraine may be due to cervical disc disease.Scalenus anticus syndrome and cardiac disease can be diagnosed or differentiated from cervical disc syndrome only by thorough investigation.Proper treatment of neck and shoulder pain is dependent upon correct diagnosis through complete history, physical examination and laboratory tests, as described in this presentation.     

Spontaneous abortion and subsequent Down syndrome livebirth

Summary Analyses of two data sets are presented, one based on nationwide hospital discharges for the USA for 1970–1971, the other for Upstate New York vital record data for 1976–1981. Summary relative risks of a Down syndrome livebirth were calculated within the three maternal age categories below 20, 20–29, and 30 years and above for those with a history of one spontaneous abortion and for those with a history of two or more, compared to those with no reported previous abortions. There was significant heterogeneity by age and reproductive history in the relative risk of an affected child. In general the trends revealed that the younger the mother and the more the number of abortions, the higher the relative risk of a Down syndrome livebirth compared to the rates for women of the same age for those with no previous abortions. Extrapolation from average maternal age specific rates on Down syndrome imply a rate per 1000 livebirths somewhere in the range of 1.1 to 11.4 for women under 20 years with a history of one spontaneous abortion, of 5.2 to 13.4 for women under 20 years with a history of two or more spontaneous abortions, and of 1.0 to 2.4 for women 20 to 29 years with a history of two or more spontaneous abortions. (Average background livebirth rates in women under 30 years are, in contrast, in the range of about 0.5 to 1.0 per 1000 and for the average woman aged 35 years, at which prenatal diagnosis is usually felt to be indicated, 2.7 per 1000.) For those in the other categories these data did not reveal clinically significant effects upon average maternal age specific rates. It is emphasized that because of limitations in the data it is not possible to refine these risks by adjusting for karyotype, the age at which the abortions occurred, or other biologic and social factors associated with embryonic and fetal death. The implications of the analyses here for genetic counseling should be regarded as preliminary and tentative.     

Gene-environment interactions in rare diseases that include common birth defects

Rare syndromes often feature specific types of birth defects that frequently are major diagnostic clues to the presence of a given disorder. Despite this specificity, not everyone with the same syndrome is equally or comparably affected, and not everyone with a specific birth defect manifests the same syndrome or is affected with all the features of a particular syndrome. A symposium sponsored by the National Institutes of Health Office of Rare Diseases, and the National Toxicology Program Center for the Evaluation of Risks to Human Reproduction attempted to explore how much of this variability is due to genetic factors and how much is due to environmental factors. The specific types of birth defects examined included cardiovascular defects, holoprosencephaly, clefts of the lip and/or palate, neural tube defects, and diaphragmatic hernias.     

Current perspectives on cardiac amyloidosis

Amyloidosis represents a group of diseases in which proteins undergo misfolding to form insoluble fibrils with subsequent tissue deposition. While almost all deposited amyloid fibers share a common nonbranched morphology, the affected end organs, clinical presentation, treatment strategies, and prognosis vary greatly among this group of diseases and are largely dependent on the specific amyloid precursor protein. To date, at least 27 precursor proteins have been identified to result in either local tissue or systemic amyloidosis, with nine of them manifesting in cardiac deposition and resulting in a syndrome termed "cardiac amyloidosis" or "amyloid cardiomyopathy." Although cardiac amyloidosis has been traditionally considered to be a rare disorder, as clinical appreciation and understanding continues to grow, so too has the prevalence, suggesting that this disease may be greatly underdiagnosed. The most common form of cardiac amyloidosis is associated with circulating amyloidogenic monoclonal immunoglobulin light chain proteins. Other major cardiac amyloidoses result from a misfolding of products of mutated or wild-type transthyretin protein. While the various cardiac amyloidoses share a common functional consequence, namely, an infiltrative cardiomyopathy with restrictive pathophysiology leading to progressive heart failure, the underlying pathophysiology and clinical syndrome varies with each precursor protein. Herein, we aim to provide an up-to-date overview of cardiac amyloidosis from nomenclature to molecular mechanisms and treatment options, with a particular focus on amyloidogenic immunoglobulin light chain protein cardiac amyloidosis.     

Further phenotypic delineation of subtelomeric (terminal) 4q deletion with emphasis on intracranial and reproductive anatomy

Hypoplastic left heart syndrome(HLHS) refers to the abnormal development of the left-sided cardiac structures, resulting in obstruction to blood flow from the left ventricular outflow tract. In addition, the syndrome includes underdevelopment of the left ventricle, aorta, and aortic arch, as well as mitral atresia or stenosis. HLHS has been reported to occur in approximately 0.016 to 0.036% of all live births. Newborn infants with the condition generally are born at full term and initially appear healthy. As the arterial duct closes, the systemic perfusion becomes decreased, resulting in hypoxemia, acidosis, and shock. Usually, no heart murmur, or a non-specific heart murmur, may be detected. The second heart sound is loud and single because of aortic atresia. Often the liver is enlarged secondary to congestive heart failure. The embryologic cause of the disease, as in the case of most congenital cardiac defects, is not fully known. The most useful diagnostic modality is the echocardiogram. The syndrome can be diagnosed by fetal echocardiography between 18 and 22 weeks of gestation. Differential diagnosis includes other left-sided obstructive lesions where the systemic circulation is dependent on ductal flow (critical aortic stenosis, coarctation of the aorta, interrupted aortic arch). Children with the syndrome require surgery as neonates, as they have duct-dependent systemic circulation. Currently, there are two major modalities, primary cardiac transplantation or a series of staged functionally univentricular palliations. The treatment chosen is dependent on the preference of the institution, its experience, and also preference. Although survival following initial surgical intervention has improved significantly over the last 20 years, significant mortality and morbidity are present for both surgical strategies. As a result pediatric cardiologists continue to be challenged by discussions with families regarding initial decision relative to treatment, and long-term prognosis as information on long-term survival and quality of life for those born with the syndrome is limited.     

Intelligence and physical features of children of women with epilepsy

The teratogenicity of maternal epilepsy has been attributed to several factors, including the antiepileptic drugs taken to prevent seizures during pregnancy, the occurrence of seizures during pregnancy, and the factors in the mother that caused her to have epilepsy. We have addressed the hypothesis that the children of women who have a history of epilepsy (seizure history), but who took no antiepileptic drugs (AED) and had no tonic-clonic seizures in pregnancy, have an increased risk of malformations and diminished intelligence. The frequency of cognitive dysfunction was determined in 57 seizure history and 57 matched control children aged 6-l6 years. The masked evaluation of the children included a physical and neurologic examination and testing with the Wechsler Intelligence Scale for Children-Revised (WISC-R) and a systematic physical examination for the features of the fetal AED syndrome. The evaluation of both parents of each child included a test of reasoning (Ravens Progressive Matrix) and a physical examination. There were no differences between the two groups of children in either IQ scores or physical features; none of the seizure history children was judged to have the "anticonvulsant face" or digit hypoplasia. This study had 80% power to rule out a difference of seven or more IQ points between the two groups, based on a two-sided test at a 5% level of significance. Our confidence in concluding that there was no difference between seizure history and control infants was strengthened by the fact that no statistically significant differences were observed with respect to multiple outcomes, including eight related measures of intelligence. Thirty (53%) of the seizure history mothers resumed taking AED after the birth of the child we evaluated. Additional studies are needed to address the teratogenicity of the antiepileptic drugs as monotherapy.     

Cardiac ultrasonography in structural abnormalities and arrhythmias. Recognition and treatment.

Fetal cardiac ultrasonography has become an important tool in the evaluation of fetuses at risk for cardiac anomalies. It can both guide prenatal treatment and assist the management and timing of delivery. We recommend that a fetal echocardiogram be done when there is a family history of congenital heart disease; maternal disease that may affect the fetus; a history of maternal drug use, either therapeutic or illegal; evidence of other fetal abnormalities; or evidence of fetal hydrops. The optimal timing of evaluation is 18 to 22 weeks'' gestation. An entire range of structural cardiac defects can be visualized prenatally, including atrioventricular septal defect, ventricular septal defect, cardiomyopathy, ventricular outlet obstruction, and complex cardiac defects. The outcome for a fetus with a recognized abnormality is unfavourable, with less than 50% surviving the neonatal period. Fetal cardiac arrhythmias are also a common occurrence, 15% in the series described here. Premature atrial or ventricular contractions are most commonly seen and usually require no treatment. Supraventricular tachycardia can result in hydrops and require in utero treatment to prevent fetal demise. Complete heart block, particularly in association with structural heart disease, has a poor prognosis for fetal survival.     

Therapy refractory hypertension in adults: aortic coarctation has to be ruled out

In patients with unexplained hypertension, especially in combination with a cardiac murmur, the presence of an aortic coarctation should always be ruled out given the high morbidity and mortality. However, particularly patients with an isolated coarctation often remain asymptomatic for years and the defect may be unnoticed even until the fifth or sixth decade of life. In the present article, we describe two patients with late detected coarctation to illustrate the clinical consequences, diagnostic clues for earlier detection and current therapeutic options to achieve optimal treatment. The key sign of an aortic coarctation, a difference in arterial blood pressure measured between the upper and lower extremities, should always be examined, followed by echocardiography. We conclude that even in case of a late detected severe coarctation, surgical or percutaneous repair has proven to be feasible and substantially effective, improving quality of life and lowering the risk of further hypertension-associated problems.     

Early influences on blood pressure: a study of children aged 5-7 years.

OBJECTIVE--To examine factors that influence blood pressure in children. DESIGN--Cross sectional study of children aged 5.0-7.0 years who had blood pressure measurements and for whom parental questionnaires were completed. SETTING--School based survey. SUBJECTS--3591 Children aged 5.0-7.5 years selected by stratified random sampling of primary schools in nine British towns (response rate 72%); 3591 were examined and their parental questionnaires were completed. Data were complete for birth rank in 3559, maternal age in 3542, maternal history of hypertension in 3524, and paternal history in 2633. RESULTS--Birth weight was inversely related to mean systolic blood pressure but only when standardised for current weight (weight standardised regression coefficient -1.83 mm Hg/kg (95% confidence interval -1.31 to -2.35). Mean diastolic pressure was similarly related to birth weight. Maternal age, birth rank, and a parental history of hypertension were all related to blood pressure. After standardisation for current weight a 10 year increase in maternal age was associated with a 1.0 mm Hg (0.4 to 1.6) rise in systolic pressure; first born children had systolic blood pressure on average 2.53 mm Hg (0.81 to 4.25) higher than those whose birth rank was greater than or equal to 4; and a maternal history of hypertension was associated with a systolic pressure on average 0.96 mm Hg (0.41 to 1.51) higher than in those with no such history. The effects described were largely independent of one another and of age and social class. The relation for birth rank was, however, closely related to that for family size. CONCLUSIONS--Influences acting in early life may be important determinants of blood pressure in the first decade. The relation between birth weight and blood pressure may reflect the rate of weight gain in infancy. The reasons for the relation with birth rank and maternal age are unknown; if confirmed they imply that delayed motherhood and smaller family size may be associated with higher blood pressure in offspring.     

Hepatic Hemodynamics and Fetal Growth: A Relationship of Interest for Further Research

Background

It is well known that hepatic hemodynamics is an important physiologic mechanism in the regulation of cardiac output (CO). It has been reported that maternal cardiac output relates to neonatal weight at birth.

Aims

In this study, we assessed the correlation between maternal hepatic vein Doppler flow parameters, cardiac output and neonatal birth weight.

Methods

Healthy women with uncomplicated second or third trimester pregnancy attending the outpatient antenatal clinic of Ziekenhuis Oost-Limburg in Genk (Belgium), had a standardized combined electrocardiogram-Doppler ultrasound with Impedance Cardiography, for measurement of Hepatic Vein Impedance Index (HVI  =  [maximum velocity – minimum velocity]/maximum velocity), venous pulse transit time (VPTT  =  time interval between corresponding ECG and Doppler wave characteristics) and cardiac output (heart rate x stroke volume). After delivery, a population-specific birth weight chart, established from a cohort of 27000 neonates born in the index hospital, was used to define customized birth weight percentiles (BW%). Correlations between HVI, VPTT, CO and BW% were calculated using Spearman''s ρ, linear regression analysis and R² goodness of fit in SPSS 22.0.

Results

A total of 73 women were included. There was a negative correlation between HVI and VPTT (ρ = −0.719, p<0.001). Both HVI and VPTT correlated with CO (ρ = −0.403, p<0.001 and ρ = 0.332, p<0.004 resp.) and with BW% (ρ = −0.341, p<0.003 and ρ = 0.296, p<0.011 resp.)

Conclusion

Our data illustrate that the known contribution of hepatic hemodynamics in the regulation of cardiac output is also true for women with uncomplicated pregnancies. Our study is the first to illustrate a potential link between maternal hepatic hemodynamics and neonatal birth weight. Whether this link is purely associative or whether hepatic vascular physiology has a direct impact on fetal growth is to be evaluated in more extensive clinical and experimental research.     

Excess of deletions of maternal origin in the DiGeorge/Velo-cardio-facial syndromes. A study of 22 new patients and review of the literature

We have determined the parental origin of the deleted chromosome 22 in 29 cases of DiGeorge syndrome (DGS) using a CA-repeat mapping within the commonly deleted region, and in one other case by using a chromosome 22 short arm heteromorphism. The CA-repeat was informative in 21 out of 29 families studied and the deleted chromosome was of maternal origin in 16 cases (72%). When these data are pooled with recent results from the literature, 24 de novo DGS, velo-cardio-facial syndrome (VCFS) and isolated conotruncal cardiac disease deletions are found to be of maternal origin and 8 of paternal origin, yielding a ² of 8 with a probability level lower than 0.01. These data, and review of the literature on familial DGS/VCFS and isolated conotruncal cardiopathies suggest that there is a strong tendency for the 22q11.2 deletions to be of maternal origin.     

Delivery of a small for gestational age infant and greater maternal risk of ischemic heart disease

Background

Delivery of a small for gestational age (SGA) infant has been associated with increased maternal risk of ischemic heart disease (IHD). It is uncertain whether giving birth to SGA infant is a specific determinant of later IHD, independent of other risk factors, or a marker of general poor health. The purpose of this study was to investigate the association between delivery of a SGA infant and maternal risk for IHD in relation to traditional IHD risk factors.

Methods and Findings

Risk of maternal IHD was evaluated in a population based cross-sectional study of 6,608 women with a prior live term birth who participated in the National Health and Nutrition Examination Survey (1999–2006), a probability sample of the U.S. population. Sequence of events was determined from age at last live birth and at diagnosis of IHD. Delivery of a SGA infant is strongly associated with greater maternal risk for IHD (age adjusted OR; 95% CI: 1.8; 1.2, 2.9; p = 0.012). The association was independent of the family history of IHD, stroke, hypertension and diabetes (family history-adjusted OR; 95% CI: 1.9; 1.2, 3.0; p = 0.011) as well as other risk factors for IHD (risk factor-adjusted OR; 95% CI: 1.7; 1.1, 2.7; p = 0.025). Delivery of a SGA infant was associated with earlier onset of IHD and preceded it by a median of 30 (interquartile range: 20, 36) years.

Conclusions

Giving birth to a SGA infant is strongly and independently associated with IHD and a potential risk factor that precedes IHD by decades. A pregnancy that produces a SGA infant may induce long-term cardiovascular changes that increase risk for IHD.     

Persistent truncus arteriosus in a rhesus monkey (Macaca mulatta)

A 47-day-old female rhesus macaque (Macaca mulatta) was examined because of a severe holosystolic heart murmur (grade 5/6) and signs of congestive heart failure. Results of physical examination, thoracic radiography, and cardiac ultrasonography confirmed an advanced stage of congestive heart failure. Due to the animal's age and clinical signs of disease, a congenital heart defect was suspected. Necropsy revealed a rare congenital heart defect known as persistent (common) truncus arteriosus.     

The Impact of Cardiac Diseases during Pregnancy on Severe Maternal Morbidity and Mortality in Brazil

Background

To evaluate maternal heart disease as a cause or complicating factor for severe morbidity in the setting of the Brazilian Network for Surveillance of Severe Maternal Morbidity.

Methods and Findings

Secondary data analysis of this multicenter cross-sectional study was implemented in 27 referral obstetric units in Brazil. From July 2009 to June 2010, a prospective surveillance was conducted among all delivery hospitalizations to identify cases of severe maternal morbidity (SMM), including Potentially Life-Threatening Conditions (PLTC) and Maternal Near Miss (MNM), using the new criteria established by the WHO. The variables studied included: sociodemographic characteristics, clinical and obstetric history of the women; perinatal outcome and the occurrence of maternal outcomes (PLTC, MNM, MD) between groups of cardiac and non-cardiac patients. Only heart conditions with hemodynamic impact characterizing severity of maternal morbidity were considered. 9555 women were included in the Network with severe pregnancy-related complications: 770 maternal near miss cases and 140 maternal death cases. A total of 293 (3.6%) cases were related to heart disease and the condition was known before pregnancy in 82.6% of cases. Maternal near miss occurred in 15% of cardiac disease patients (most due to clinical-surgical causes, p<0.001) and 7.7% of non-cardiac patients (hemorrhagic and hypertensive causes, p<0.001). Maternal death occurred in 4.8% of cardiac patients and in 1.2% of non-cardiac patients, respectively.

Conclusions

In this study, heart disease was significantly associated with a higher occurrence of severe maternal outcomes, including maternal death and maternal near miss, among women presenting with any severe maternal morbidity.     

Preventive health care, 1999 update: 2. Echocardiography for the detection of a cardiac source of embolus in patients with stroke

OBJECTIVE: To develop guidelines for the use of echocardiography in the investigation of patients with stroke. OPTIONS: (1) Routine transthoracic echocardiography (TTE); (2) routine transesophageal echocardiography (TEE); (3) routine TTE followed by TEE if the TTE findings are noncontributory; (4) selective TTE or TEE in patients with cardiac disease who would not otherwise receive anticoagulant therapy. OUTCOMES: This article reviews the available evidence on the yield of TTE and TEE in detecting cardiac sources of cerebral emboli in patients with stroke, the effectiveness of treatment for cardiac sources of emboli and the effectiveness of screening echocardiography for secondary stroke prevention. EVIDENCE: MEDLINE was searched for relevant articles published from January 1966 to April 1998; also reviewed were additional articles identified from the bibliographies and citations obtained from experts. BENEFITS, HARMS AND COSTS: Echocardiography can detect intracardiac masses (thrombus, vegetation or tumour) in about 4% (with TTE) to 11% (with TEE) of stroke patients. The yield is lower among patients without clinical evidence of cardiac disease by history, physical examination, electrocardiography or chest radiography (less than 2%) than among patients with clinical evidence of cardiac disease (less than 19%). The risks of echocardiography to patients are small. TTE has virtually no risks, and TEE is associated with cardiac, pulmonary and bleeding complications in 0.18%. Patients with an identified intracardiac thrombus are at increased risk for embolic events (absolute risk uncertain, range 0%-38%), and this appears to be reduced with anticoagulant therapy (absolute risk reduction uncertain). Anticoagulant therapy carries a risk of major hemorrhage of 1% to 3% per year. The overall effectiveness of echocardiography in the prevention of recurrent stroke is unknown. VALUES: The strength of evidence was evaluated using the methods of the Canadian Task Force on Preventive Health Care. RECOMMENDATIONS: There is fair evidence to recommend echocardiography in patients with stroke and clinical evidence of cardiac disease by history, physical examination, electrocardiography or chest radiography (grade B recommendation). There is insufficient evidence to recommend for or against TEE in patients with normal results of TTE (grade C recommendation). There is insufficient evidence to recommend for or against routine echocardiography in patients (including young patients) without clinical cardiac disease (grade C recommendation). Routine echocardiography is not recommended for patients with clinical cardiac disease who have independent indications for or contraindications to anticoagulant therapy (grade D recommendation). There is fair evidence to recommend anticoagulant therapy in patients with stroke and intracardiac thrombus (grade B recommendation). There is insufficient (no) evidence to recommend for or against any specific therapy for patent foramen ovale (grade C recommendation). VALIDATION: The findings of this analysis were reviewed through an iterative process by the members of the Canadian Task Force on Preventive Health Care.