Cardiac Calcifications in Adults with Congenital Heart Defects Dan G. Halpern, MD*†‡§ Michael L. Steigner, MD¶** Sanjay P. Prabhu, MD,**†† Anne Marie Valente, MD,*†‡§ and Stephen P. Sanders, MD*§‡‡§§ *Adult Congenital Heart Disease and Pulmonary Hypertension Service, Department of Cardiology, ††Department of Radiology, ‡‡Department of Pathology, §§Department of Cardiac Surgery, Boston Children’s Hospital, †Department of Medicine, Division of Cardiology, ¶Department of Radiology, Brigham and Women’s Hospital, ‡Department of Medicine, § Department of Pediatrics, and **Department of Radiology, Harvard Medical School, Boston, Mass, USA ABSTRACT
Objective. We investigated the type and extent of calcification in a series of heart specimens from adult congenital heart disease patients because recent autopsy observations suggested a high prevalence of calcification. Design. We used computed tomography to examine seven heart specimens from adults (>18 years old) with a congenital heart defect collected with permission from the family during a recent 3-year period. Clinical data regarding diagnosis, history, and imaging studies were recorded. The 3D data sets were reviewed after reformatting as maximum intensity projection and volumetric renderings to determine the pattern and extent of calcium deposition. Results. Five of the seven hearts had extensive calcifications in one or more of three patterns: atherosclerosis associated in the three oldest cases; surgery associated in four of five hearts that had undergone heart surgery; and myocardial calcification remote from surgical sites in two cases. Myocardial calcification was associated with regional dysfunction and was present in the three patients that died suddenly and unexpectedly. Conclusion. Cardiac calcification was frequent in our series of heart specimens from adults with congenital heart defects, was often but not uniformly associated with prior surgery, and, in our small series, was associated with regional dysfunction and sudden death. Key Words. Calcifications; Myocardium; Pericardium; Adult Congenital Heart Disease
alcification of heart structures and tissue substitutes has been reported in infants and children with congenital heart defects.1–5 Calcium deposits in arteries, degenerating valves, and even the myocardium are seen in adult subjects.6–9 Although recognized, heart calcification in adults with congenital heart defects has not been characterized. Recent observations of extensive calcification of heart structures at autopsy in a few of these patients led us to examine this process more systematically. Methods
All heart specimens from adults (>18 years old) with a history of a congenital heart defect in the Cardiac Registry at the Boston Children’s HospiCongenit Heart Periodicals, Dis. 2015;10:396–402 © 2015 Wiley Inc.
tal collected during a recent 3-year interval were reviewed. The patients’ family had given written informed consent in all cases to maintain the specimen in the collection and to use it for research and teaching. The patients’ records were reviewed for clinical history, cause of death, and antemortem imaging studies and laboratory data. Cause of death was determined by review of available medical records and death certificates. Death was classified as secondary to heart failure if it complicated worsening heart failure, as defined by evidence of at least one of the following: orthopnea, nocturnal dyspnea, pulmonary edema, increasing peripheral edema or renal hypoperfusion related to cardiac dysfunction, or radiological signs of congestive heart failure.10,11 Sudden death was defined as death occurring within 1 hour of onset of acute symptoms.11 C 2015 Wiley Periodicals, Inc. V Congenit Heart Dis. 2015;••:••–••
Halpern et397 al.
Cardiac Calcifications in ACHD 2 The heart (and lungs if present) was imaged by computed tomography (CT) using a 64-detector scanner (Sensation 64; Siemens, Erlangen, Germany) (120 kV, 140 mAs, 0.6 mm slice thickness) yielding an isotropic 3D data set (voxel size 0.6 × 0.6 × 0.6 mm). The CT images were reviewed on a Fuji Synapse workstation (Fujifilm Medical Systems, Stamford, CT, USA) and 3D reconstructions of the data sets were created using Voxar software (Voxar, Toshiba Medical Systems, Tokyo, Japan) or a Vitrea 3D workstation (Vital Images, Toshiba Medical, Systems). Images were reviewed after reformatting in maximum intensity projection mode and as 3D volumetric reconstructions. The 3D volumetric images were segmented automatically with Voxar software, using a threshold for calcium density that maximized the differentiation between calcified and uncalcified tissue. Multi-object segmentation was used on the Vitrea workstation utilizing a combination of semiautomatic and manual segmentation. Antemortem cardiac magnetic resonance (CMR) exams were reviewed for anatomy and regional and global function. Results
Nine adults with a congenital heart defect underwent autopsy at our institution during the 3-year Table 1.
period. Specimens from seven of the nine were available in the Cardiac Registry and comprise the study population (Table 1). All the patients had been followed and treated at this institution. None of the patients had systemic hypercalcemia, renal insufficiency, or other metabolic disorder known to be associated with metastatic calcification. The most common pathology encountered was tetralogy of Fallot (three cases, two with pulmonary atresia). Other diagnoses included complete atrioventricular canal, heterotaxy syndrome with hypoplastic left ventricle, ventricular septal defect (VSD) with cleft mitral valve and patent ductus arteriosus, and partially anomalous pulmonary venous connection (scimitar syndrome). The average number of surgical procedures was two per patient, although two patients had not undergone any cardiac surgery. The cause of death was believed to be cardiac in six cases: arrhythmia in Cases 1, 3, and 5, heart failure in Case 2, and pulmonary vascular disease in Cases 6 and 7. Cardiac calcifications were detected by CT scan in five hearts (Cases 1–5) but not in the other two hearts (Cases 6 and 7). Three basic types of calcification were observed: (1) typical atherosclerosisassociated type; 2) surgery-associated type at surgical sites; and 3) myocardial calcification at sites not directly involved in surgical repair.
Summary of Cases
Prior cardiac surgery (age in years)
Potts shunt (8) Complete repair (17)
TOF and PA, multiple AP collaterals
TOF and PA, multiple muscular VSDs, LAD from RCA
CAVC, subaortic stenosis
Waterston shunt (2) Complete repair with RV–PA conduit (9) Conduit revision (12, 23) Balloon dilatation (43) Melody valve (45) CAVC repair (