A rare missense mutation in MYH6 associates with non-syndromic coarctation of the aorta.

Aims: Coarctation of the aorta (CoA) accounts for 4-8% of congenital heart defects (CHDs) and confers substantial morbidity despite treatment. It is increasingly recognized as a highly heritable condition. The aim of the study was to search for sequence variants that affect the risk of CoA. Methods and results: We performed a genome-wide association study of CoA among Icelanders (120 cases and 355 166 controls) based on imputed variants identified through whole-genome sequencing. We found association with a rare (frequency = 0.34%) missense mutation p.Arg721Trp in MYH6 (odds ratio = 44.2, P = 5.0 × 10-22), encoding the alpha-heavy chain subunit of cardiac myosin, an essential sarcomere protein. Approximately 20% of individuals with CoA in Iceland carry this mutation. We show that p.Arg721Trp also associates with other CHDs, in particular bicuspid aortic valve. We have previously reported broad effects of p.Arg721Trp on cardiac electrical function and strong association with sick sinus syndrome and atrial fibrillation. Conclusion: Through a population approach, we found that a rare missense mutation p.Arg721Trp in the sarcomere gene MYH6 has a strong effect on the risk of CoA and explains a substantial fraction of the Icelanders with CoA. This is the first mutation associated with non-familial or sporadic form of CoA at a population level. The p.Arg721Trp in MYH6 causes a cardiac syndrome with highly variable expressivity and emphasizes the importance of sarcomere integrity for cardiac development and function.

[Cardiac arrest in a teenager - a case report]. / Hjartastopp hja unglingsstulku - sjukratilfelli.

Cardiac arrest is rarely seen in children and teenagers. We present a 12-year old girl with cardiac arrest following myocardial infarction, that required prolonged cardiac massage and extracorporeal-membranous-oxygenation (ECMO). At coronary angiography the left main coronary artery (LMCA) was stented for a suspected coronary dissection. The contraction of the heart improved and the ECMO-treatment was discontinued a week later. The patient was discharged home, but six months later a coronary artery bypass surgery was performed for in-stent restenosis. Further work-up with computed tomography (CT) showed that the LMCA originated from the right aortic sinus instead of the the left one. This case demonstrates how life threatening myocardial infarction can be caused by coronary artery anomalies.

[Fetal echocardiography in Iceland 2003-2007; indications and outcomes]. / Fósturhjartaómskodanir á Islandi 2003-2007; ábendingar og útkoma.

OBJECTIVE: The aim of the study was to evaluate the indications and outcomes of fetal echo (FE) and determine which indication has the highest detection rate for congenital heart disease (CHD). METHODS: The referral indications and results of FE performed in Iceland during 2003-2007 were reviewed. Information regarding gestational age at diagnosis, nuchal translucency, pregnancy outcome, autopsy results and postnatal diagnosis were obtained from medical records. RESULTS: During the five year period 1187 FE were performed. Structural heart defect was diagnosed in 73 fetuses. The most common referral indication was family history of CHD (631;53.2%) which led to diagnosis of 18 heart defects prenatally (2.9%). The second most common referral indication was increased nuchal translucency (159) and abnormal cardiac findings were present in 16 cases (10.1%). A total of 30 women were referred for FE because of abnormal four chamber view (AFCV) which resulted in the diagnosis of 22 (73.3%) major heart defects, either incompatible with life or requiring immediate intervention after birth. Other indications led mostly to the diagnoses of minor defects. CONCLUSIONS: AFCV is the most important predictor for diagnosis of structural heart defects. 2,5% were referred for FE due to AFCV which led to diagnosis of 30% of all heart defects, all of which were major. Key words: fetal echocardiography, indications, congenital heart disease.

[Surgery for coarctation of the aorta in Iceland 1990-2006]. / Arangur skurdadgerda vid medfaeddri ósaedarthrengingu hjá börnum á Islandi 1990-2006.

BACKGROUND AND AIMS: Coarctation of the aorta (CoA) is a congenital narrowing of the aorta, distal to the origin of the left subclavian artery. Treatment consists of surgical excision but balloon angioplasty is also a treatment option for selected patients. The aim of this study was to evaluate surgical outcome in children operated for CoA in Iceland. MATERIAL AND METHODS: All Icelandic children (<18 yrs.) operated for CoA in Iceland between 1990 and 2006. Patients operated abroad (n=17) or managed conservatively (n=12) were excluded. Mean follow up period was 8.5 +/- 4.3 years. RESULTS: Of 67 children diagnosed with CoA, 38 were operated on in Iceland (mean age 36 +/- 58 months, and 22 male and 16 female patients), 10 required immediate surgery for cardiac failure and eight were diagnosed incidentally. Extended end-to-end anastomosis was the most common procedure (n=31). Subclavian-flap aortoplasty was performed in seven patients. Average operation time was 134 min. and mean aortic closure time was 21 +/- 9 min. Hypertension (58%) and heart failure (11%) were the most common postoperative complications. Recoarctation developed 35 +/- 56 months after surgery in seven patients (18%) and was successfully treated with balloon angioplasty. There were no operative deaths and no patients developed paraplegia. One patient suffered an ischemic injury to the brachial plexus. Today all of the patients are alive, except for one patient that died four months after surgery from heart failure. CONCLUSION: Majority of Icelandic patients with CoA are operated on in Iceland with excellent outcome, both regarding short term complications and long term survival.

Severe labetalol overdose in an 8-month-old infant.

We report a case of a large labetalol overdose in an eight-month-old infant that was being treated for hypertension following surgery for coarctation of the aorta. Labetalol, both alpha and beta adrenergic blocking agent was used for treating postoperative hypertension. By mistake, the patient was given an extremely high dose of labetalol intravenously (17.2 mg.kg(-1)). Remarkably, the medication error had a surprisingly limited clinical effect on the infant who survived the incident. We discuss the pharmacokinetic, pharmocodynamic and possible explanations for this fortunate turn of events.

Sensitivity for detection of patent foramen ovale increased with increasing number of contrast injections: a descriptive study with contrast transesophageal echocardiography.

OBJECTIVE: We sought to study the diagnostic yield of increasing numbers of contrast injections for detection of patent foramen ovale (PFO) during transesophageal echocardiography. METHODS: Contrast was injected twice during each of 10 provocations to 30 patients screened for PFO. Injections were given during quiet respiration, early Valsalva (starting 3-5 seconds before injection), late Valsalva (starting 3-5 seconds after injection), Mueller maneuver, coughing, bed tilt during early Valsalva, after nitroglycerin spray during both quiet respiration, and early Valsalva. RESULTS: The number of detected PFOs increased as the number of injections increased (r = 0.79, P < .01). Five injections per patient detected all 11 large PFOs. To eventually detect all 14 PFOs among the 30 study patients required a total of 11 injections per patient. CONCLUSION: The sensitivity for PFO detection increased when additional contrast injections were given. At least 5 injections are required to safely detect or rule out the presence of a PFO.

Sizing of atrial septal defects in adults.

In a retrospective study of 51 consecutive patients undergoing transcatheter closure of secundum type atrial septal defects (ASDs), we examined the reliability of transesophageal echocardiography (TEE) prior to catheterization and compared the diameter with that obtained by balloon measurement during catheterization. The TEE diameter was 16.3+/-4.6 mm compared with 22.5+/-6.0 mm for the stretched diameter obtained during catheterization (p<0.001). There was no gender difference. The degree of left-to-right shunting correlated poorly with the size of the defect. We conclude that although TEE is accurate for diagnosis of an ASD, the measurement of its size to determine the size of the closure device is at best inaccurate.

[Tetralogy of fallot in iceland from 1968 to 2001.].

OBJECTIVE: We reviewed our experience regarding tetralogy of Fallot (TOF) in Iceland over a 34 year period from 1968 to 2001. We looked at incidence, diagnosis,treatment and outcome and any changes in these parameters during the study period. MATERIALS AND METHODS: Data were obtained from hospital records containing echocardiographic, cardiac catheterization, surgical and autopsy reports. RESULTS: Forty six children were diagnosed as having TOF during the study period. The incidence was 1:3209 births and male to female ratio 1.2:1. The followup period was from two months to 33 years (median 10.5 years). Thirty seven patients had classic TOF, six had TOF with pulmonal atresia and three had other anatomical variants. Six children had chromosomal abnormalities and another five had physical anomalies outside of the heart. Nine children (24.3%) with classic TOF had a systemic to pulmonary artery shunt placed. Thirty eight (82.6%) of the patients have had corrective cardiac surgery and five in addition are scheduled to undergo such procedure in the near future. Three patients died before corrective surgery. All corecctive operations were carried out abroad. Half of the patients had difficulties following surgery and two (5.3%) died in the immediate post operative period. Of the 46 children born with TOF during the study period, seven (15.2%) have died and three are lost to followup. Corrective heart surgery had been done in four of the seven patients who died. Of the 36 patients alive in whom current information is available, 32 (88.9%) are in good physical condition leading full active lives. Corrective surgery which is planned for the other four is expected to improve their condition. Of 30 patients with classic TOF, two are being treated for arrhythmia and four have had interventional cardiac catheterizations three to 24 years following corrective surgery. In 10 of 30 pateints with classic TOF the most recent echocardiogram showed significant abnormalities. Most commonly this consisted of moderate to severe enlargement of the right ventricle with significant pulmonary valve insufficiency. CONCLUSIONS: TOF is a complex congenital heart defect with high incidence of coexistant chromosomal and physical abnormalities. Progress in recent years regarding surgical treatment and care of these patients in general has dramatically improved outcome.

Congenital cardiac malformations in Iceland from 1990 through 1999.

INTRODUCTION AND BACKGROUND: About 1% of live-born children have congenital malformations of the heart. The aim of our study was to investigate the incidence of such defects in children born in Iceland during a period of 10 years, extending from 1990 through 1999. MATERIALS AND METHODS: Information about the patients was obtained from medical records from two hospitals that cover the whole country, a private clinic of pediatric cardiologists, an echocardiography database, autopsy reports, and death certificates. We investigated the distribution of specific malformations, the age at diagnosis, the symptoms leading to the diagnosis, the source of referral, and treatment and quality of life. RESULTS: Between 1990 and 1999, there were 44,013 live births in Iceland, of which 740 patients were diagnosed with congenital cardiac malformations, accounting for 1.7% of the live-born children. The distribution was made up of 338 patients with ventricular septal defect (45.7%), 90 with atrial septal defect (12.2%), 85 with patency of the arterial duct (11.5%), 48 with pulmonary valvar stenosis (6.5%), 38 with a bicuspid aortic valve (5.1%), 28 with aortic coarctation (3.8%), 22 with tetralogy of Fallot (3.0%), 14 with transposed great arteries (1.9%), 11 with aortic stenosis (1.5%), 10 with atrioventricular septal defect and common atrioventricular orifice (1.4%), 9 with mitral valvar regurgitation (1.2%), 7 with sub-aortic stenosis (0.9%), and 5 with hypoplasia of the left heart (0.7%). Extracardiac anomalies were seen in 89 patients (12.0%). Chromosomal defects were seen in 36 patients, of whom 28 had Down's syndrome. DISCUSSION: The annual incidence of diagnosis of patients with congenital cardiac malformations increased during the period of study. This was noted for minor defects, but the incidence of the major anomalies did not alter. Our observed yearly incidence, at 1.7%, was higher than noted in a previous study covering the years 1985 through 1989, and is also higher than in other population-based studies. The most likely explanation is the fact that access to pediatric cardiologists in Iceland is very good. Diagnosis, registration, and follow-up are conducted by only a few cardiologists, and take place at a single center for pediatric cardiology.

[Congenital heart defects in Iceland 1990-1999.].

OBJECTIVE: About 1% of live born children have congenital heart defects (CHD). Knowledge of the true incidence of CHD is important because of the risk of bacterial endocarditis in patients with heart defects. This knowledge could also serve as a basis for research on the etiology of CHD. The aim of our study was to investigate the incidence of CHD in children born in Iceland during a ten year period, from 1990 to 1999. A similar study on CHD was carried out in Iceland for children born 1985-1989. The incidence of CHD in the present study was compared to the previous and to similar studies from other countries. MATERIAL AND METHODS: Information about the patients were obtained from medical records from two hospitals covering the whole country, a private clinic of pediatric cardiologists, echocardiography database, autopsy reports and death certificates. Distribution of specific heart defects, age at diagnosis, symptoms leading to the diagnosis, referral pattern, treatment and quality of life was investigated. Other congenital defects, chromosomal defects and syndromes in the patients were studied. Premature children with patent ductus arteriosus (PDA) and children with patent foramen ovale (PFO) or atrial septal defect (ASD) smaller than four millimeters were excluded. We also studied the incidence of bicuspid aortic valve (BAV). All diagnoses were confirmed with echocardiography and in some cases cardiac catheterization. RESULTS: Between 1990 and 1999 there were 44,013 live births in Iceland, 740 children were diagnosed with a CHD or 1.7% of live born children. Yearly incidence varied from 1.04% of live births in 1991 to 2.34% in 1997. Male/female ratio was 1/1. The distribution of the defects was following: ventricular septal defect (VSD) 338 (45.7%), ASD 90 (12.2%), PDA 85 (11.5%), valvar pulmonal stenosis 48 (6.5%), BAV 38 (5.1%), coarctation of the aorta 28 (3.8%), tetrology of Fallot 22 (3.0%), transposition of the great arteries 14 (1.9%), aortic stenosis 11 (1.5%), common atrioventricular septal defect 10 (1.4%), mitral valve regurgitation 9 (1.2%), sub-aortic stenosis 7 (0.9%) and hypoplastic left heart syndrome 5 (0.7%). Other defects were less frequent. About 47% of children with CHD were diagnosed either before birth or before discharge from the delivery institution. A cardiac murmur on examination was the most common symptom leading to the diagnosis of CHD, 631 patients (85.3%). Extracardiac anomalies were seen in 89 patients (12.0%). Chromosomal abnormalities were seen in 36 patients of whom 28 had Down's syndrome. The majority or 499 patients have no symptoms but are still in follow-up, 20 patients have daily symptoms and/or receive medical treatment and 27 patients have died. Conslusions: Annual incidence of patients diagnosed with a CHD has increased during the study period. This is observed in minor CHD but the incidence of major defects does not alter. This yearly incidence (1.7%) is higher than in the previous study, where it was 1.1%. The difference can partly be explained by the BAVs, which were excluded in the 1985-1989 study. But the number of CHD diagnosed each year has increased, this being most pronounced in the last three years. The annual incidence in our study is also higher than in other population studies. The most likely explanation for the higher incidence in our study is the fact that access to pediatric cardiologists is very good in Iceland. Diagnosis, registration and follow-up is conducted by only a few cardiologists for the whole nation and takes place at a single pediatric cardiology center. Of 740 patients diagnosed with CHD in the study period 713 are alive. The outcome of the therapy is good and the majority of the patients has no symptoms.