Sergey Yalonetsky

Cardiac Magnetic Resonance Imaging and the Assessment of Ebstein Anomaly in Adults

No published studies have evaluated the role of cardiac magnetic resonance (CMR) imaging for the assessment of Ebstein anomaly. Our objective was to evaluate the right heart characteristics in adults with unrepaired Ebstein anomaly using contemporary CMR imaging techniques. Consecutive patients with unrepaired Ebstein anomaly and complete CMR studies from 2004 to 2009 were identified (n = 32). Volumetric measurements were obtained from the short-axis and axial views, including assessment of the functional right ventricular (RV) end-diastolic volume (EDV) and end-systolic volume. The volume of the atrialized portion of the right ventricle in end-diastole was calculated as the difference between the total RVEDV and the functional RVEDV. The reproducibility of the measurements in the axial and short-axis views was determined within and between observers. The median value derived from the short-axis and axial views was 136 ml/m(2) (range 59 to 347) and 136 ml/m(2) (range 63 to 342) for the functional RVEDV, 153 ml/m(2) (range 64 to 441) and 154 ml/m(2) (range 67 to 436) for the total RVEDV, 49% (range 32% to 46%) and 50% (range 40% to 64%) for the functional RV ejection fraction, respectively. The axial measurements demonstrated lower intraobserver and interobserver variability than the short-axis approach for all values, with the exception of the intraobserver functional RVEDV and interobserver total RVEDV for which the limits of agreement and variance were not significantly different between the 2 views. In conclusion, measurements of right heart size and systolic function in patients with Ebstein anomaly can be reliably achieved using CMR imaging. Axial imaging appeared to provide more reproducible data than that obtained from the short-axis views.

Clinical characteristics of coronary artery disease in adults with congenital heart defects

BACKGROUND There are now more adults with congenital heart disease than children. This aging cohort is at risk for acquired heart diseases such as coronary artery disease (CAD). The purpose of the study was to examine the clinical features of the CAD in adults with congenital heart disease. METHODS A retrospective chart review was performed. The clinical characteristics of adults with congenital heart disease and angiographically confirmed atherosclerotic CAD were examined. RESULTS One hundred and forty-one adults with CAD (69% male) were identified from a total of 12,124 patients (1%) seen in our congenital cardiac clinic. The most common cardiac diagnoses were atrial septal defect, bicuspid aortic valve disease, tetralogy of Fallot and coarctation of the aorta. We identified 7 adults with Eisenmenger physiology and CAD. The mean age of diagnosis of CAD was 56 ±13years. Twenty patients had premature CAD (14%) presenting before age 40years. Traditional risk factors of patients with CAD were common and were present in the majority (82%) of patients. While many adults had symptoms of angina or myocardial infarction, a significant proportion (38%) were asymptomatic. The age at diagnosis in patients with coarctation of the aorta was younger than other subgroups (48±13years). Seventy-seven percent (109/141) underwent percutaneous or surgical coronary interventions. CONCLUSION Atherosclerotic coronary artery disease may coexist with congenital heart disease. Coronary artery disease in adults with congenital heart disease typically occurs later in adulthood and in patients with traditional cardiovascular risk factors. This study highlights the need for cardiovascular risk factor screening and therapy when indicated.

Right heart characteristics and exercise parameters in adults with Ebstein anomaly: New perspectives from cardiac magnetic resonance imaging studies

BACKGROUND The utility of cardiac magnetic resonance imaging (CMR) for assessment of adults with Ebstein anomaly is not well-defined. We sought to evaluate CMR characteristics in this population and to relate these to exercise parameters. METHODS We analyzed CMR studies in adults with unrepaired Ebstein anomaly for measures of severity of Ebstein disease, including atrialized, functional and total right ventricular (RV) volumes, ejection fraction (EF) and severity index (area of atrialized RV+right atrium/functional RV+left ventricle+left atrium). We related these CMR values to cardiopulmonary exercise test measurements. RESULTS Twenty-seven adults (mean age 41 ± 14 years, 70% female) were included. Functional RV end-diastolic volume (EDV) was 150 ± 68 mL/m(2) and atrialized RVEDV was 25 ± 24 mL/m(2). In 17 patients (63%), the functional RVEDV was enlarged (>114 mL/m(2)). Percent predicted peak VO2 for the population was 65 ± 20%. On univariable analysis, peak VO2 was inversely related to atrialized RVEDV (p = 0.011), total RVEDV (p = 0.041), functional RVEDV/left ventricular EDV ratio (p = 0.015) and magnitude of tricuspid valve displacement (p = 0.031). In the multivariate model, the only CMR factor to relate to peak VO2 was atrialized RVEDV (p = 0.011, β = -0.48). No significant correlations were found between CMR measures and heart rate response or ventilatory response to exercise. CONCLUSION In adults with unrepaired Ebstein anomaly, atrialized RV volume was independently related to aerobic capacity. The volume of the atrialized RV is a novel CMR measure which may express severity of disease. Further research is needed to evaluate the prognostic relevance of this exploratory work.

Psychological functioning and health-related quality of life (HRQoL) in older patients following percutaneous closure of the secundum atrial septal defect (ASD)

To characterize quality of life and psychological well-being in the new growing population of older patients who underwent trans-catheter closure of the secundum ASD. Twenty-seven patients, aged 60 years and older, who underwent trans-catheter ASD closure and 27 age and gender matched controls answered the hospital anxiety and depression scale and the cardiac-specific module of the health-related quality of life (HRQoL) questionnaire. Pre- and post-ASD closure pulmonary artery pressure (Pap), and the New York Heart Association (NYHA) functional capacity class were recorded from medical records. Almost 77% improvement in Pap and 57% improvement in functional status were found. More than 70% reported low/mild depressive symptoms and 59% reported low/mild anxiety in both groups. Almost 78% of ASD patients and 89% of controls reported high/very high levels of HRQoL. Significantly better QoL was reported by the controls. Lower post-ASD closure Pap scores were associated with better QoL, but were not significantly related to levels of depression and anxiety scores. Preoccupation with the ASD closure was related to higher pre-closure Pap scores, worse QoL, and higher depressive and anxiety symptoms. Following ASD closure, depression and anxiety symptoms were in the low range, and HRQoL scores for most patients were in the high range.

Mitral valve destruction by Hodgkin's lymphoma-associated Loefler endocarditis.

We present a case of nearly total posterior mitral leaflet destruction due to Loeffler endocarditis associated with Hodgkin’s lymphoma in a 15-year-old adolescent. The patient was treated medically with subsequent surgical mitral valve replacement. Cardiac aspects of hypereosinophilic syndrome are also discussed.

Clinical evaluation of a fully automated model-based algorithm to calculate left ventricular volumes and ejection fraction using multidetector computed tomography

Objectives: To evaluate feasibility and accuracy of a fully automatic algorithm (FAA) for calculating left ventricular volumes and ejection fraction (LVEF) from multidetector computed tomography (MDCT) studies versus a previously validated method based on Simpsons method serving as our reference standard (RS), and left ventriculography (LVG), in patients with acute chest pain (ACP). Methods: 23 patients admitted with ACP underwent ECG-gated MDCT, as well as LVG during their hospitalization. MDCT based end-diastolic, end-systolic and stroke volumes (EDV, ESV, SV) and LVEF were calculated using the RS and the FAA. Results: One patient was excluded after FAA failure to detect contours. In the remaining 22 patients, mean±SD LVEF measurements were RS 61±11%, FAA 59±11% (r = 0.91 versus RS), LVG 57±16% (r = 0.6 versus RS). In comparison to RS, FAA overestimated EDV by 10.1±8.5 ml, ESV by 7.3±6.4 ml and SV by 3.6±8.6 ml, and underestimated LVEF measurements by 2.7±4.6%, related to contour smoothing. LVEF by FAA was within 8% of RS for all patients except one. In contrast, LVG differed significantly from RS. Conclusions: The evaluated FAA obtained accurate, clinically relevant results for left ventricular volumes and LVEF relative to the RS.

Late high degree atrioventricular block after percutaneous closure of a perimembranous ventricular septal defect

Atrioventricular block is an important complication after percutaneous closure of perimembranous ventricular septal defects. In the majority of cases, it appears in early or in the midterm of closure. We present a patient who developed symptomatic Mobitz 2 second-degree atrioventricular block 3 years following percutaneous closure of such a defect.

Morphologic, Mechanical, Conductive, and Hemodynamic Changes Following Transcatheter Closure of Atrial Septal Defect

OBJECTIVE The secundum type of atrial septal defect (ASD) is a common congenital cardiac anomaly. Transcatheter closure of the defect is the preferable therapeutic approach to avoid potential future complications. This work extends the data collected so far regarding the electrocardiographic, morphologic, hemodynamic, and mechanical changes following the procedure. DESIGN From April 2002 to October 2003, 42 consecutive patients underwent successful transcatheter closure of secundum type ASD. They were sampled for different parameters by transthoracic echocardiography before the procedure and at three different points over the next 4 years, and analyzed in two age groups: children and adults. RESULTS The dimensions of the chambers normalized throughout the study period. Abnormal movement of the interventricular septum normalized mostly during the first month, but its thickness increased gradually to normal levels during the 4 years of the study. High elevated pulmonary artery pressure values began declining to near normal levels from the second month following the procedure. The stroke volume and the right bundle branch block pattern improved throughout the study period. CONCLUSIONS Transcatheter ASD closure is followed by morphologic, conductive, and hemodynamic changes at different time intervals during the first years and results in normalization or near normalization of the hearts structure and function.

Left ventricular segmental dysfunction following percutaneous transcatheter closure of a membranous ventricular septal defect

Percutaneous device closure of membranous ventricular septal defects is an attractive alternative for surgical treatment. A patient with left ventricular segmental dysfunction with infarct like ECG pattern following transcatheter membranous VSD closure is presented. Possible pathophysiological mechanisms of this phenomenon are discussed.

A homozygous variant in mitochondrial RNase P subunit PRORP is associated with Perrault syndrome characterized by hearing loss and primary ovarian insufficiency

Perrault syndrome is a rare autosomal recessive condition characterised by sensorineural hearing loss in both sexes and primary ovarian insufficiency in 46 XX, females. It is genetically heterogeneous with biallelic variants in six genes identified to date (HSD17B4, HARS2, LARS2, CLPP, C10orf2 and ERAL1). Most genes possessing variants associated with Perrault syndrome are involved in mitochondrial translation. We describe a consanguineous family with three affected individuals homozygous for a novel missense variant c.1454C>T; p.(Ala485Val) in KIAA0391, encoding proteinaceous RNase P (PRORP), the metallonuclease subunit of the mitochondrial RNase P complex, responsible for the 5’-end processing of mitochondrial precursor tRNAs. In RNase P activity assays, RNase P complexes containing the PRORP disease variant produced ~35-45% less 5’-processed tRNA than wild type PRORP. Consistently, the accumulation of unprocessed polycistronic mitochondrial transcripts was observed in patient dermal fibroblasts, leading to an observable loss of steady-state levels of mitochondrial oxidative phosphorylation components. Expression of wild type KIAA0391 in patient fibroblasts rescued tRNA processing. Immunohistochemistry analyses of the auditory sensory epithelium from postnatal and adult mouse inner ear showed a high level of PRORP in the efferent synapses and nerve fibres of hair cells, indicating a possible mechanism for the sensorineural hearing loss observed in affected individuals. We have identified a variant in an additional gene associated with Perrault syndrome. With the identification of this disease-causing variant in KIAA0391, reduced function of each of the three subunits of mitochondrial RNase P have now been associated with distinct clinical presentations. Author Summary Perrault syndrome is a rare genetic condition which results in hearing loss in both sexes and ovarian dysfunction in females. Perrault syndrome may also cause neurological symptoms in some patients. Here, we present the features and genetic basis of the condition in three sisters affected by Perrault syndrome. The sisters did not have pathogenic variants in any of the genes previously associated with Perrault syndrome. We identified a change in the gene KIAA0391, encoding PRORP, a subunit of the mitochondrial RNase P complex. Mitochondrial RNase P is a key enzyme in RNA processing in mitochondria. Impaired RNA processing reduces protein production in mitochondria, which we observed in patient cells along with high levels of unprocessed RNA. When we expressed wild type PRORP in patient cells, the RNA processing improved. We also investigated PRORP localisation in the mouse inner ear and found high levels in the synapses and nerve fibers that transmit sound. It may be that disruption of RNA processing in the mitochondria of these cells causes hearing loss in this family.