Alexander Kovacevic

Prenatal screening for major congenital heart disease: Assessing performance by combining national cardiac audit with maternity data

Objective Determine maternity hospital and lesion-specific prenatal detection rates of major congenital heart disease (mCHD) for hospitals referring prenatally and postnatally to one Congenital Cardiac Centre, and assess interhospital relative performance (relative risk, RR). Methods We manually linked maternity data (3 hospitals prospectively and another 16 retrospectively) with admissions, fetal diagnostic and surgical cardiac data from one Congenital Cardiac Centre. This Centre submits verified information to National Institute for Cardiovascular Outcomes Research (NICOR-Congenital), which publishes aggregate antenatal diagnosis data from infant surgical procedures. We included 120 198 unselected women screened prospectively over 11 years in 3 maternity hospitals (A, B, C). Hospital A: colocated with fetal medicine, proactive superintendent, on-site training, case-review and audit, hospital B: on-site training, proactive superintendent, monthly telemedicine clinics, and hospital C: sonographers supported by local obstetrician. We then studied 321 infants undergoing surgery for complete transposition (transposition of the great arteries (TGA), n=157) and isolated aortic coarctation (CoA, n=164) screened in hospitals A, B, C prospectively, and 16 hospitals retrospectively. Results 385 mCHD recorded prospectively from 120 198 (3.2/1000) screened women in 3 hospitals. Interhospital relative performance (RR) in Hospital A:1.68 (1.4 to 2.0), B:0.70 (0.54 to 0.91), C:0.65 (0.5 to 0.8). Standardised prenatal detection rates (funnel plots) demonstrating inter-hospital variation across 19 hospitals for TGA (37%, 0.00 to 0.81) and CoA (34%, 0.00 to 1.06). Conclusions Manually linking data sources produced hospital-specific and lesion-specific prenatal mCHD detection rates. More granular, rather than aggregate, data provides meaningful feedback to improve screening performance. Automatic maternal and infant record linkage on a national scale, requires verified, prospective maternity audit and integration of health information systems.

Palivizumab-Resistant Human Respiratory Syncytial Virus Infection in Infancy

Palivizumab-resistant respiratory syncytial virus was isolated from an infant treated with palivizumab. A stable mutation at codon 276 led to a nearly complete resistance to palivizumab. Additional studies revealed a second mutation at codon 272. Further passage of the virus led to a complete loss of binding of palivizumab.

Natural history of 107 cases of fetal aortic stenosis from a European multicenter retrospective study

Fetal aortic valvuloplasty (FV) aims to prevent fetal aortic valve stenosis progressing into hypoplastic left heart syndrome (HLHS), which results in postnatal univentricular (UV) circulation. Despite increasing numbers of FVs performed worldwide, the natural history of the disease in fetal life remains poorly defined. The primary aim of this study was to describe the natural history of fetal aortic stenosis, and a secondary aim was to test previously published criteria designed to identify cases of emerging HLHS with the potential for a biventricular (BV) outcome after FV.

Fetal aortic valvuloplasty: investigating institutional bias in surgical decision-making

Fetal aortic valvuloplasty may prevent the progression of aortic stenosis to hypoplastic left heart syndrome and allow biventricular rather than univentricular postnatal treatment. This study aimed to investigate whether blinded simulation of a multidisciplinary team approach aids interpretation of multicenter data to uncover institutional bias in postnatal decision‐making following fetal cardiac intervention for aortic stenosis.

Malonic aciduria: long-term follow-up of new patients detected by newborn screening

AbstractMalonic aciduria is an extremely rare autosomal recessive inborn error of metabolism. We present clinical, biochemical and genetic information for several years of follow-up of new malonic aciduria patients who were diagnosed by newborn screening. These data are discussed with regard to treatment options and possible diagnostic pitfalls. The cases presented here show that the course of malonic aciduria is unpredictable and can even significantly differ in two siblings harbouring identical mutations. Early treatment can lead to the rapid improvement of cardiomyopathy in the course of malonic aciduria. Biochemical parameters seem to be variable and can intermittently be undetectable in the blood or urine samples of affected patients. Therefore, confirmatory tests following a positive newborn screening should be taken with caution and include both malonyl carnitine detection in dried blood spots and urinary organic acid analysis as initial measures. Conclusion: Patients with a suspected or confirmed diagnosis of malonic aciduria should undergo thorough diagnostic procedures and be regularly screened for complications such as cardiomyopathy even when they are asymptomatic in order to ensure early therapy of treatable complications.

Mucolipidosis II complicated by severe pulmonary hypertension.

Mucolipidosis II (ML II) is an autosomal recessive lysosomal enzyme targeting disorder leading to fatal outcome in childhood mostly due to respiratory insufficiency. Typical cardiac involvement includes thickening and deformation of mitral and aortic valve and dilated or hypertrophic cardiomyopathy [1–3]. We report the clinical course of a child with confirmedML II in whom pulmonary hypertension (PH)was diagnosed after he had been referred to our hospital for further evaluation of cardiomegaly.

Fetal hemodynamic response to aortic valvuloplasty and postnatal outcome: a European multicenter study

Fetal aortic stenosis may progress to hypoplastic left heart syndrome. Fetal valvuloplasty (FV) has been proposed to improve left heart hemodynamics and maintain biventricular (BV) circulation. The aim of this study was to assess FV efficacy by comparing survival and postnatal circulation between fetuses that underwent FV and those that did not.

Severely impaired wound healing in a Fontan patient after neurosurgery: a novel topic in univentricular heart physiology?

In 1971, Fontan and Baudet introduced a surgical procedure that established a physiologic circulation in three patients with tricuspid atresia [1]. Over the last three decades, the Fontan operation and its modifications have widely been accepted as the final palliation for most forms of congenital heart disease with a single ventricular chamber. The particular hemodynamics in a patient with Fontan physiology with increased central venous pressure (CVP) and limited preload reserve must be considered carefully during anesthesia and surgery for non-cardiac indications. Elevated CVP may contribute to significant blood loss [2]. We report here the case of a Fontan patient following a standard neurosurgical procedure. During the postoperative course, disturbed wound healing involving dura mater, calvaria as well as galea and skin created multiple problems, which currently appear to be underreported in the context of Fontan physiology.