Comprehensive Cardiac Assessment Research Articles

Very low intravenous contrast volume protocol for computed tomography angiography providing comprehensive cardiac and vascular assessment prior to transcatheter aortic valve replacement in patients with chronic kidney disease

BackgroundTranscatheter aortic valve replacement (TAVR) is a lifesaving procedure for many patients high risk for surgical aortic valve replacement. The prevalence of chronic kidney disease (CKD) is high in this population, and thus a very low contrast volume (VLCV) computed tomography angiography (CTA) protocol providing comprehensive cardiac and vascular imaging would be valuable. Methods52 patients with severe, symptomatic aortic valve disease, undergoing pre-TAVR CTA assessment from 2013–4 at Columbia University Medical Center were studied, including all 26 patients with CKD (eGFR<30 mL/min) who underwent a novel VLCV protocol (20 mL of iohexol at 2.5 mL/s), and 26 standard-contrast-volume (SCV) protocol patients. Using a 320-slice volumetric scanner, the protocol included ECG-gated volume scanning of the aortic root followed by medium-pitch helical vascular scanning through the femoral arteries. Two experienced cardiologists performed aortic annulus and root measurements. Vascular image quality was assessed by two radiologists using a 4-point scale. ResultsVLCV patients had mean (±SD) age 86 ± 6.5, BMI 23.9 ± 3.4 kg/m2 with 54% men; SCV patients age 83 ± 8.8, BMI 28.7 ± 5.3 kg/m2, 65% men. There was excellent intra- and inter-observer agreement for annular and root measurements, and excellent agreement with 3D-transesophageal echocardiographic measurements. Both radiologists found diagnostic-quality vascular imaging in 96% of VLCV and 100% of SCV cases, with excellent inter-observer agreement. ConclusionsThis study is the first of its kind to report the feasibility and reproducibility of measurements for a VLCV protocol for comprehensive pre-TAVR CTA. There was excellent agreement of cardiac measurements and almost all studies were diagnostic quality for vascular access assessment.

Cardiovascular magnetic resonance reference ranges for the heart and aorta in Chinese at 3T.

BackgroundCardiovascular magnetic resonance (CMR) reference ranges have not been well established in Chinese. Here we determined normal cardiac and aortic reference ranges in healthy Singaporean Chinese and investigated how these data might affect clinical interpretation of CMR scans.MethodsIn 180 healthy Singaporean Chinese (20 to 69 years old; males, n = 91), comprehensive cardiac assessment was performed using the steady state free precision technique (3T Ingenia, Philips) and images were analysed by two independent observers (CMR42, Circle Cardiovascular Imaging). Measurements were internally validated using standardized approaches: left ventricular mass (LVM) was measured in diastole and systole (with and without papillary muscles) and stroke volumes were compared in both ventricles. All reference ranges were stratified by sex and age; and “indeterminate/borderline” regions were defined statistically at the limits of the normal reference ranges. Results were compared with clinical measurements reported in the same individuals.ResultsLVM was equivalent in both phases (mean difference 3.0 ± 2.5 g; P = 0.22) and stroke volumes were not significantly different in the left and right ventricles (P = 0.91). Compared to females, males had larger left and right ventricular volumes (P < 0.001 for all). Indexed LVM was significantly higher in males compared to females (50 ± 7 versus 38 ± 5 g/m2, respectively; P < 0.001). Overall, papillary muscles accounted for only ~2 % of the total LVM. Indexed atrial sizes and aortic root dimensions were similar between males and females (P > 0.05 for all measures). In both sexes, age correlated negatively with left and right ventricular volumes; and positively with aortic sinus and sinotubular junction diameters (P < 0.0001 for all). There was excellent agreement in indexed stroke volumes in the left and right ventricles (0.1±5.7mL/m2, 0.7±6.2 mL/m2, respectively), LVM (0.6±6.4g/m2), atrial sizes and aortic root dimensions between values reported in clinical reports and our measured reference ranges.ConclusionsComprehensive sex and age-corrected CMR reference ranges at 3T have been established in Singaporean Chinese. This is an important step for clinical practice and research studies of the heart and aorta in Asia.Electronic supplementary materialThe online version of this article (doi:10.1186/s12968-016-0236-3) contains supplementary material, which is available to authorized users.

Utilizing human embryonic stem cell-derived cardiomyocytes on multiple analytical platforms for a more comprehensive cardiac safety assessment

Utilizing human embryonic stem cell-derived cardiomyocytes on multiple analytical platforms for a more comprehensive cardiac safety assessment

Determinants in treatment decision-making in older patients with symptomatic severe aortic stenosis

BackgroundThree treatment options are available for patients with aortic stenosis: surgical aortic valve replacement (SAVR), transcatheter aortic valve implantation (TAVI) and medical treatment (MT). However, little is known about how Heart Team treatment decisions are made under routine conditions. The aim of this study was to identify the cardiac and geriatric components associated with treatment decision-making in older patients with symptomatic severe aortic stenosis. MethodsBetween 2011 and 2013, 337 consecutive patients ≥75 years old referred for pre-operative evaluation in Nantes University Hospital had a comprehensive cardiac and geriatric assessment. In this observational retrospective study, relationships between treatment decision-making and cardiac or geriatric components were evaluated through multivariable models. ResultsSurgical aortic valve replacement was proposed to 108 patients, TAVI to 131 and medical treatment to 98 patients. Mean age was 83±4 years and 51% were women. Geriatric components associated with treatment decision-making between SAVR vs. TAVI were age (p<0.001, OR=0.790), comorbidity score (p=0.027, OR=0.86), functional status (p<0.001, OR=1.46), and gait speed (p<0.001, OR=0.23). Cardiac components associated with decision-making between SAVR vs. TAVI were history of previous cardiac surgery (p<0.001, OR=0.09), left ventricular ejection fraction <50% (p<0.001, OR=0.14), coronary artery disease requiring revascularization (p=0.019, OR=0.4). Between TAVI vs. medical treatment, only history of previous cardiac surgery and presence of another severe valve disease were significant. ConclusionComorbidities, functional status and physical performance, were significantly associated with the consensual treatment decision-making, independently of cardiac components in older patients with symptomatic severe aortic stenosis.

101 Ethnic Variation in Hypertrophic Cardiomyopathy

Introduction Hypertrophic cardiomyopathy (HCM) is a genetic disorder with significant variability in its clinical phenotype. Most major studies in HCM to date have been largely based on Caucasian patients, but there are some indications that racial background may have an important effect on the disease course. In other areas (such as athletes and hypertensive patients) black patients have been shown to be significantly different to white patients in terms of ECG and echocardiographic appearances. In this study we have used a large single centre population to determine the effect of racial group on baseline phenotype and clinical outcomes in HCM. Methods The case records of sequential patients with hypertrophic cardiomyopathy referred to our cardiomyopathy clinic were reviewed. Patients were asked to identify their racial group using the standard Office of National Statistics classification. Patients who identified themselves as mixed race were excluded. Patients underwent comprehensive cardiac assessment at their baseline visit, and were followed up regularly, for a mean of 7 years. Results Records were available for 2248 patients (95 Black/African/Caribbean/Black British (B), 216 Asian/Asian British (A), 1937 White (W)). Asian patients were more likely to be male (W 66%, B 66%, A 78%, p At baseline assessment, there were differences in the morphological pattern of left ventricular hypertrophy on echo, with more B patients having apical and concentric distributions of hypertrophy, while W and A patients mostly displayed asymmetric septal hypertrophy (p During follow-up, there were significant differences between ethnic groups in a combined end-point of mortality and cardiac transplant (Annual rates W 1.4%, B 1.7%, A 0.6%, p 0.02), but there were no significant differences in a secondary combined end-point of sudden cardiac death, aborted sudden death, and appropriate ICD therapy (Annual rates W 0.4%, B 0.4%, A 0.2%, p 0.4). W patients were significantly more likely to receive a pacemaker (Annual rates W 1.8%, B 0.9%, A 0.8%, p Conclusions In this large single centre study of hypertrophic cardiomyopathy, there were significant differences between racial groups in terms of their clinical phenotype at presentation and their long term outcomes. Further work is required to try and understand the different genetic and social factors which lead to these different disease patterns.

The cardiomyopathy in Friedreich's ataxia — New biomarker for staging cardiac involvement

BackgroundPatients with autosomal-recessively inherited Friedreich's ataxia (FA) may develop a hypertrophic cardiomyopathy (CM), which potentially progresses towards a life-limiting problem. The typical features of this CM and the sequence of progression are widely unknown. MethodsThirty-two consecutive patients with genetically confirmed FA were included. All patients received resting electrocardiogram (ECG), 24-hour Holter-ECG, echocardiography with speckle tracking imaging, cardiac magnetic resonance imaging (cMRI) with late enhancement imaging (for replacement fibrosis), and measurement of high-sensitive troponin-T (hsTNT). In addition, morphological parameters were retrospectively compared to data obtained five years before. ResultsBased on criteria comprising ejection fraction (<55%), left ventricular end-diastolic posterior wall thickness (LVPWT≥11mm), fibrosis on cMRI, hsTNT≥14ng/ml, or T-wave-inversion, in all but two patients a CM could be detected (94%). Using these criteria we propose the following staging: a) mild CM (n=5, 16%; T-wave-inversion only); b) intermediate CM (n=4, 13%; T-wave-inversion with hypertrophy but no fibrosis); c) severe CM (n=13, 41%; fibrosis with raised hsTNT); and d) end-stage CM (n=8; 25%; ejection-fraction<55%). All patients with end-stage CM also showed fibrosis on cMRI, T-wave-inversion, marked elevation in hsTNT, and a decrease in LVPWT during the last five years (from 10.7±1.2mm to 9.5±1.3mm, p=0.025). In addition, 38% suffered from supraventricular tachycardia on Holter-ECG. ConclusionsA comprehensive cardiac assessment will unravel established CM in almost all patients with FA with electrocardiographic abnormalities as earliest signs. Advanced stages can be characterized by elevated hsTNT and replacement fibrosis leading to recession of hypertrophy, reduction of global myocardial function, and electrical instability.

Myocardial fibrosis in stroke survivors

Stroke survivors are most likely to die of cardiac death, yet few undergo comprehensive cardiac assessment to look for reversible causes. Myocardial fibrosis (MF) is not only the hallmark of cardiomyopathy, but also a substrate for sudden cardiac death, ventricular tachyarrhythmia and heart failure. Procollagen carboxyl-terminal telopeptide (PICP) was found to be a marker of MF. The relationship between PICP and cardiac abnormalities in stroke survivors is unknown. We recently showed that MF in stroke survivors can be treated by spironolactone and amiloride in a randomised placebo-controlled cross-over study with reduction in PICP levels and QTc [1].

TCT-254 Very Low Intravenous Contrast Dose (20cc) Protocol for Computed Tomography Angiography (CTA) Providing Comprehensive Cardiac and Vascular Assessment for Transcatheter Aortic Valve Replacement (TAVR) in Patients with Chronic Kidney Disease (CKD)

TAVR is a lifesaving procedure for many patients at high risk for surgical aortic valve replacement. The prevalence of CKD and risk for contrast-induced nephropathy in this population is high. A very low contrast dose CTA protocol enabling comprehensive cardiac and vascular imaging would be valuable

Systemic sclerosis: detection of early subclinical diffuse myocardial fibrosis and impaired left ventricular strain by cardiovascular magnetic resonance

Background Systemic sclerosis (SSc) is characterized by widespread tissue fibrosis including the myocardium. Diffuse myocardial fibrosis can be detected non-invasively by extracellular volume (ECV) imaging based on preand postcontrast T1 measurements using cardiovascular magnetic resonance (CMR). We hypothesized that multiparametric CMR, including T1 mapping, can detect subclinical myocardial involvement and provide a comprehensive cardiac assessment in patients with SSc.

Overview of safety pharmacology.

Safety pharmacology entails the assessment of the potential risks of novel pharmaceuticals for human use. As detailed in the ICH S7A guidelines, safety pharmacology for drug discovery involves a core battery of studies on three vital systems: central nervous (CNS), cardiovascular (CV), and respiratory. Primary CNS studies are aimed at defining compound effects on general behavior, locomotion, neuromuscular coordination, seizure threshold, and vigilance. The primary CV test battery includes an evaluation of proarrhythmic risk using in vitro tests (hERG channel and Purkinje fiber assays) and in vivo measurements in conscious animals via telemetry. Comprehensive cardiac risk assessment also includes full hemodynamic evaluation in a large, anesthetized animal. Basic respiratory function can be examined in conscious animals using whole-body plethysmography. This allows for an assessment of whether the sensitivity to respiratory-depressant effects can be enhanced by exposure to increased CO2 . Other safety pharmacology topics detailed in this unit are the timing of such studies, ethical and animal welfare issues, and statistical evaluation.

Circulation : Clinical Summaries

<i>Circulation</i> : Clinical Summaries

Increased Prevalence of Congenital Heart Defects in Monozygotic and Dizygotic Twins

Smaller studies and many case series reports indicate that congenital heart defects may be more common in monochorionic twins than in dichorionic twins and singletons. We investigated congenital heart defect occurrence in all twins and 5% of all singletons born in Denmark in 1977-2001 and followed through 2006 by linking the Danish Twin Registry and Statistics Denmark registers including the National Medical Birth Register and the Danish National Patient Register. Among 41 525 twin individuals, a total of 584 twins (1.4%) had a congenital heart defect registered in the Danish National Patient Register, whereas the corresponding numbers for singletons were 648 of 74 473 (0.87%; P<0.001; ie, a 63% [95% confidence interval, 45-82%] increased risk for congenital heart defect for twins). Patent ductus arteriosus and coarctation of aorta occurred >3 times as often in twins as in singletons, at 3.9 (95% confidence interval, 2.6-5.8) and 3.1 (95% confidence interval, 1.5-6.4), respectively. The increased occurrence in twins was also found in sensitivity analyses including only inpatients or only surgically treated cases regardless of whether preterm patent ductus arteriosus was included. We were not able to demonstrate a higher risk for congenital heart defect among monozygotic twins compared with dizygotic twins, and the congenital heart defect occurrence was also increased in dizygotic twins, who are all dichorionic. Congenital heart defect is more common in twins than in singletons, and the increased occurrence is not restricted to monochorionic twins. Intrauterine surveillance and a postnatal comprehensive cardiac assessment for both twins may be considered regardless of chorionicity and zygosity.

Computed tomography myocardial perfusion and myocardial blood flow by oxygen 15 positron emission tomography

Introduction: Non-invasive computed tomography imaging has the potential to achieve comprehensive cardiac assessment in a rapid and low radiation dose assessment. We assessed computed tomography coronary angiography (CTCA) and computed tomography myocardial perfusion (CTP) compared to invasive coronary angiography (ICA) and fractional flow reserve (FFR). In addition we assessed myocardial blood flow using oxygen-15 labelled water positron emission tomography (PET). Methods: Contrast enhanced, electrocardiogram gated CTCA and adenosine stress CTP was performed in 31 patients (69% male) using a 320 multidetector scanner. Significant coronary disease was assessed on a per vessel basis as a stenosis greater than 50% with corresponding hypoperfusion on CTP. All patients underwent ICA and significant coronary artery disease was assessed as a stenosis greater than 70% and/or an FFR less than 0.8. Five patients underwent rest and adenosine stress oxygen-15 PET. The total coronary resistance (TCR) at rest and stress was calculated as the mean arterial pressured divided by myocardial blood flow. Results: The mean age was 63 years (95% CI 61, 66), body mass index 28 kg/m2 (27, 30) and radiation dose 564 mGy.cm (437, 692). The sensitivity, specificity, negative predictive value and positive predictive value of CTCA/CTP for detecting significant coronary artery disease as compared to ICA/FFR were 85%, 84%, 30% and 92% respectively. TCR at rest and stress were 80 (72, 87) and 31 (28, 33) for normal regions compared to 97 (43, 151) and 33 (32, 34) for regions with hypoperfusion on CTP. ![Figure][1] Figure 1. CTCA/CTP compared to ICA/FFR Conclusion: The diagnostic accuracy of CTCA/CTP imaging compares well with ICA/FFR. CTP may detect additional areas of hypoperfusion and oxygen-15 PET imaging will assist the assessment of these technologies. [1]: pending:yes

Cardiac toxicity in cancer survivors

Cardiac disease is a major concern for cancer survivors, and this can be manifested as cardiac dysfunction from myocardial damage, valvular disease, atherosclerosis, and/or pericardial disease. In this "dialogue" between select European and American investigators, present current perspectives (both similarities and differences) are presented regarding the diagnosis and management of cardiac disease among cancer survivors, with a focus on left ventricular (LV) systolic dysfunction and heart failure. The authors conclude that comprehensive cardiac risk assessment is necessary to optimally manage all cancer survivors, and the integration of common definitions is necessary. Ongoing and future research will need to incorporate cardiovascular management principles in the long-term assessment of cancer survivors. Cardiac biomarkers, troponin, and the natriuretic peptides are becoming essential in the management of cardiac disease in cancer survivors coupled with periodic use of sophisticated imaging tools. Recognition of specific cancer therapy and the increased cardiovascular risk is an ongoing task that will remain of paramount importance for optimal outcomes among cancer survivors.

381 Burden of Non-Alcoholic Fatty Liver Disease in the Veterans Administration

calculated, after adjustment for LDL, diabetes, metabolic syndrome, and BMI. RESULTS: When hepatic steatosis was added to the traditional Framinghammodel, it was independently associated with greater risk of CCS.100 {Odds ratio 2.85, 95% CI (1.26-6.44) p=0.012}. Compared to the Framingham model, the addition of hepatic steatosis non-significantly increased the c-statistic (0.776 vs 0.789, p=0.31). However, there was a significant value of IDI (Absolute IDI=0.17, Relative IDI=13.6%, p=0.045). This indicated that the spread in predicted probabilities between events and non-events separated by an additional 14%, after inclusion of hepatic steatosis . In addition, CCS .100 was independently associated with an increased risk of development of hepatic steatosis {0dds ratio 2.4, 95% CI (1.08-5.54) p= 0.03} CONCLUSION: Hepatic steatosis is an independent and a strong predictor of CCS.100 Agatston units in asymptomatic patients. It is associated with an increased risk of CAD beyond that expected from traditional Framingham risk factors or metabolic syndrome. The converse that significant CAD is an independent risk factor for hepatic steatosis was also demonstrated. Additional studies may determine the value of hepatic steatosis in models for comprehensive cardiac risk assessment.

Will the new advantages provided by PET in myocardial perfusion imaging help nuclear cardiology survive the test of time against conventional radiological techniques?

Dear Sir, In a very interesting article published in the European Journal of Nuclear Medicine and Molecular Imaging [1], Flotats et al. provide reasonable and interesting findings about the use of Rb PET in the evaluation of patients with and without coronary artery disease (CAD). It is widely accepted that, due to the small risk of complications related to conventional coronary angiography, which has up to now been the gold standard for detecting CAD, noninvasive cardiac imaging is now central to the diagnosis and management of patients with known or suspected CAD. Nuclear cardiology has played an important role in recent years: single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) has been widely validated for the diagnosis and prognosis of cardiac disease, and the technique is heavily embedded in national and international guidelines [2]. In recent years, after a long period dominated by SPECT imaging, the availability of promising perfusion PET tracers such as Rb (1995) and, more recently, N-ammonia has led to various studies comparing PET and SPECT techniques. Although data obtained more than 15 years ago support the superiority of PET over SPECT for diagnosing CAD, it is unclear whether PET would still be found to be superior because of major advances in SPECT instrumentation [3] and imaging protocols [4]. The excellent work by Flotats et al., although comparing PET with standard protocol SPECT acquisition, seems to indicate that PET perfusion imaging may be a better weapon to help nuclear cardiology survive the test of time. It is undoubtedly clear that more recently cardiac magnetic resonance (CMR) may be able to play an important role in CAD detection and evaluation. During a reasonably short acquisition time (on average 45–60 min) CMR may offer a comprehensive cardiac assessment, including qualitative and quantitative functional analysis, detection of valve anomalies, accurate demonstration of infarct size and identification of inducible ischaemia [5]. Information from scanning the heart during pharmacologically induced stress is also provided. With regard to the other noninvasive techniques, a range of agents (i.e. dobutamine, adenosine, dipyridamole) are available, but adenosine is the most widely used because major cardiac events are rare and because the short half-life of the drug allows easier and safer management of patients both under normal conditions and in the event of adverse events. After the administration of adenosine, inducible ischaemia may be indirectly heralded by the onset of regional wall motion abnormalities demonstrated by the acquisition of cine MR images; however, the sensitivity of this technique is quite poor. More commonly, the effects of adenosine are directly assessed through the acquisition of a stack of images with high temporal resolution (typically one image every heartbeat) during the first pass of a bolus of gadolinium-based contrast agent. Although a compromise must be reached between temporal resolution, spatial resolution and image coverage, on modern scanners stress perfusion may be assessed in at least three short-axis sections. When the patient’s heart rate allows it, one or two long-axis sections F. Caobelli (*) : C. Pizzocaro :U. P. Guerra Department of Nuclear Medicine, Fondazione Poliambulanza, Via Bissolati 57, 25100 Brescia, Italy e-mail: fedefournier@libero.it

Screening Adult Survivors of Childhood Cancer for Cardiomyopathy: Comparison of Echocardiography and Cardiac Magnetic Resonance Imaging

To compare two-dimensional (2D) echocardiography, the current method of screening for treatment-related cardiomyopathy recommended by the Children's Oncology Group Guidelines, to cardiac magnetic resonance (CMR) imaging, the reference standard for left ventricular (LV) function. Cross-sectional, contemporaneous evaluation of LV structure and function by 2D and three-dimensional (3D) echocardiography and CMR imaging in 114 adult survivors of childhood cancer currently median age 39 years (range, 22 to 53 years) exposed to anthracycline chemotherapy and/or chest-directed radiation therapy. In this survivor population, 14% (n = 16) had an ejection fraction (EF) less than 50% by CMR. Survivors previously undiagnosed with cardiotoxicity (n = 108) had a high prevalence of EF (32%) and cardiac mass (48%) that were more than two standard deviations below the mean of normative CMR data. 2D echocardiography overestimated the mean EF of this population by 5%. Compared with CMR, 2D echocardiography (biplane method) had a sensitivity of 25% and a false-negative rate of 75% for detection of EF less than 50%, although 3D echocardiography had 53% and 47%, respectively. Twelve survivors (11%) had an EF less than 50% by CMR but were misclassified as ≥ 50% (range, 50% to 68%) by 2D echocardiography (biplane method). Detection of cardiomyopathy was improved (sensitivity, 75%) by using a higher 2D echocardiography cutoff (EF < 60%) to detect an EF less than 50% by the reference standard CMR. CMR identified a high prevalence of cardiomyopathy among adult survivors previously undiagnosed with cardiac disease. 2D echocardiography demonstrated limited screening performance. In this high-risk population, survivors with an EF 50% to 59% by 2D echocardiography should be considered for comprehensive cardiac assessment, which may include CMR.

The Heart in Friedreich Ataxia

Background— This cross-sectional study provides a practical approach for the clinical assessment of Friedreich ataxia (FA) cardiomyopathy (FA-CM). Methods and Results— A comprehensive cardiac assessment, including standard echocardiography, color Doppler myocardial imaging, cardiac magnetic resonance imaging, ECG, and exercise stress testing, was performed in 205 FA patients. To assess myocardial hypertrophy in FA-CM, the end-diastolic interventricular septal wall thickness (IVSTd) was found to be the best echocardiographic parameter compared with cardiac magnetic resonance imaging–determined left ventricular mass. With the use of this parameter, 4 groups of patients with FA-CM could be defined. Patients with normal values for IVSTd (31.7%) were classified as having no FA-CM. Patients with an IVSTd exceeding the predicted normal IVSTd were classified as having mild FA-CM (40%) if IVSTd exceeded the normal value by &lt;18% or as having intermediate FA-CM (16.1%) if IVSTd exceeded the normal value by ≥18%. Patients with ejection fraction &lt;50% were classified as having severe FA-CM (12.2%). In addition to increased myocardial mass, severe FA-CM was further characterized by dilatation of the left ventricle, reduced systolic strain rate of the posterior wall, and ECG abnormalities. Regional myocardial function correlated negatively with FA-CM groups. Younger patients had a tendency for more advanced FA-CM. Importantly, no clear correlation was found between FA-CM groups and neurological function. Conclusions— We provide and describe a readily applicable clinical grouping of the cardiomyopathy associated with FA based on echocardiographic IVSTd and ejection fraction data. Because no distinct interrelations between FA-CM and neurological status could be determined, regular follow-up of potential cardiac involvement in FA patients is essential in clinical practice. Clinical Trial Registration— https://www.clinicaltrials.gov . Unique identifier: NCT00905268.

Twin–twin transfusion syndrome, coarctation of the aorta and hypoplastic aortic arch: A case series report

The twin-twin transfusion syndrome (TTTS) complicates 10-30% of monochorionic pregnancies. The incidence of pulmonary stenosis and endocardial fibroelastosis is especially high in the recipient twin. We report a novel finding of four cases of coarctation of the aorta and hypoplastic aortic arch in the donor to raise awareness of cardiac lesions in twins affected by TTTS. Retrospective review of both neonatal database and mortality data from 2002 to 2007 with cross-validation from the local tertiary cardiology unit data (1998-2006) to identify children presenting with coarctation who were also twins. We identified four monochorionic twin pairs affected by the TTTS, delivered between 25 weeks and 36 weeks' gestation, where the donor was found to have coarctation of the aorta or a hypoplastic aortic arch. In addition, two of the four recipients also had cardiac abnormalities. There was a high mortality rate of 30% for both twins, and a high morbidity rate, especially for neurological sequelae. We believe that the types of abnormalities seen may be explained by the altered fetal blood flow and haemodynamics in TTTS. Given the increased prevalence of congenital heart disease in TTTS, with an increased risk of coarctation in the donor twin and pulmonary stenosis in the recipient, intra-uterine surveillance and a post-natal comprehensive cardiac assessment for both twins is warranted.

Deletion of JAM‐C, a candidate gene for heart defects in Jacobsen syndrome, results in a normal cardiac phenotype in mice

The 11q terminal deletion disorder (11q-) is a rare chromosomal disorder caused by a deletion in distal 11q. Fifty-six percent of patients have clinically significant congenital heart defects. A cardiac "critical region" has been identified in distal 11q that contains over 40 annotated genes. In this study, we identify the distal breakpoint of a patient with a paracentric inversion in distal 11q who had hypoplastic left heart and congenital thrombocytopenia. The distal breakpoint mapped to JAM-3, a gene previously identified as a candidate gene for causing HLHS in 11q-. To determine the role of JAM-3 in cardiac development, we performed a comprehensive cardiac phenotypic assessment in which the mouse homolog for JAM-3, JAM-C, has been deleted. These mice have normal cardiac structure and function, indicating that haplo-insufficiency of JAM-3 is unlikely to cause the congenital heart defects that occur in 11q- patients. Notably, we identified a previously undescribed phenotype, jitteriness, in most of the sick or dying adult JAM-C knockout mice. These data provide further insights into the identification of the putative disease-causing cardiac gene(s) in distal 11q, as well as the functions of JAM-C in normal organ development.