Dominica Zentner

Familial cardiological and targeted genetic evaluation: Low yield in sudden unexplained death and high yield in unexplained cardiac arrest syndromes

BACKGROUND It has been reported that cardiological screening and genetic evaluation in relatives of families with sudden unexplained death syndrome and unexplained cardiac arrest (UCA) may uncover a heritable etiology in a significant proportion of families. OBJECTIVE To evaluate the yield of a comprehensive evaluation protocol of a large unselected cohort of consecutive families with autopsy-negative sudden unexplained death syndrome (termed sudden arrhythmic death syndrome [SADS]) and UCA. METHODS We studied (1) 109 consecutive families (411 relatives) referred with 1 or more sudden deaths in the family and (2) 52 consecutive probands with UCA (91 relatives) referred by cardiologists between January 2007 and December 2012. A comprehensive cardiological screening was performed followed by targeted genetic evaluation if a clinical phenotype was proven or suspected. Diagnosis was made by a multidisciplinary team using published clinical criteria. RESULTS A diagnosis was made in 19 of 109 families with SADS (yield 18%), with the majority having long QT syndrome (LQTS). Diagnosis varied according to proband age, with LQTS most common in the very young (≤20 years) and Brugada syndrome in the older age probands (≥40 years) (P = .03). In contrast, a diagnosis was made in 32 of 52 families with UCA (yield 62%), the majority of which had LQTS and Brugada syndrome. No clinical or circumstantial factors increased the likelihood of diagnosis in families with either SADS or UCA. CONCLUSIONS In contrast to previously published series, a comprehensive strategy of cardiological evaluation and targeted genetic testing in more than 100 families with SADS was found to have a lower diagnostic yield (18%). Diagnostic yield in families with UCA was approximately 4 times higher (62%), which is consistent with the published literature.

Deterioration in cardiac systolic and diastolic function late in normal human pregnancy

The aim of the present study was to undertake a longitudinal study of systolic and diastolic cardiac function during normal pregnancy. At a median of 16 weeks of gestation, 100 primiparous women underwent echocardiography, including tissue Doppler imaging, determining left ventricular mass, cardiac output, systolic and diastolic velocities, and wall stress. A total of 32 were assessed again at a median of 37 weeks of gestation. Non-pregnant control estimates (n=9) were obtained by averaging four separate measures over two menstrual cycles. Initially, the pregnant women had significantly higher pulse rates than controls, associated with greater ventricular wall stress (two-tailed P value=0.015), and systolic (two-tailed P value=0.005) and diastolic (two-tailed P value=0.018) lateral wall myocardial velocities, but no differences in systolic blood pressure, left ventricular mass or cardiac output. By 37 weeks of gestation, increased blood pressure (two-tailed P value<0.001) and left ventricular mass (two-tailed P value=0.002) were associated with a significant increase in ventricular wall stress (two-tailed P value<0.001), and reductions in septal systolic (two-tailed P value=0.004) and septal and lateral early diastolic (two-tailed P value<0.001) myocardial velocities. The diastolic velocities at 37 weeks correlated inversely with maternal weight and age. In conclusion, by term pregnancy, an increase in ventricular wall stress is accompanied by a deterioration in cardiac function.

Progression of atrial remodeling in patients with high-burden atrial fibrillation: Implications for early ablative intervention.

BACKGROUND Advanced atrial remodeling predicts poor clinical outcomes in human atrial fibrillation (AF). OBJECTIVE The purpose of this study was to define the magnitude and predictors of change in left atrial (LA) structural remodeling over 12 months of AF. METHODS Thirty-eight patients with paroxysmal AF managed medically (group 1), 20 undergoing AF ablation (group 2), and 25 control patients with no AF history (group 3) prospectively underwent echocardiographic assessment of strain variables of LA reservoir function at baseline and at 4, 8, and 12 months. In addition, P-wave duration (Pmax,, Pmean) and dispersion (Pdis) were measured. AF burden was quantified by implanted recorders. Twenty patients undergoing ablation underwent electroanatomic mapping (mean 333 ± 40 points) for correlation with LA strain. RESULT Group 1 demonstrated significant deterioration in total LA strain (26.3% ± 1.2% to 21.7% ± 1.2%, P < .05) and increases in Pmax (132 ± 3 ms to 138 ± 3 ms, P < .05) and Pdis (37 ± 2 ms to 42 ± 2 ms, P < .05). AF burden ≥10% was specifically associated with decline in strain and with P-wave prolongation. Conversely, group 2 manifest improvement in total LA strain (21.3% ± 1.7% to 28.6% ± 1.7%, P <.05) and reductions in Pmax (136 ± 4 ms to 119 ± 4 ms, P < .05) and Pdis (47 ± 3 ms to 32 ± 3 ms, P < .05). Change was not significant in group 3. LA mean voltage (r = 0.71, P = .0005), percent low voltage electrograms (r = -0.59, P = .006), percent complex electrograms (r = -0.68, P = .0009), and LA activation time (r = -0.69, P = .001) correlated with total strain as a measure of LA reservoir function. CONCLUSION High-burden AF is associated with progressive LA structural remodeling. In contrast, AF ablation results in significant reverse remodeling. These data may have implications for timing of ablative intervention.

Fertility and pregnancy in the Fontan population

BACKGROUND Women with a Fontan circulation are deemed at significantly increased risk of maternal morbidity and mortality during pregnancy. Publications describe a small number of pregnancies worldwide and a high rate of miscarriage. We compiled the experience of women enrolled in the Australia and New Zealand Fontan (ANZ) Registry with regard to menarche, contraceptive use, pregnancy advice and pregnancy outcomes. METHODS Women within the ANZ Fontan Registry were contacted and asked to consent to receiving sequential questionnaires. RESULTS 156 women ≥ 18 years of age (including 4 deceased individuals) were identified, 101 women consented and 97 completed the initial questionnaire. Women were aged (median) 25 years (23-32); menarche occurred at a median 14 years (13-16). A wide variety of contraceptive methods was reported. 81% of women reported having received advice that pregnancy carried an increased risk or was inadvisable. Pregnancy was reported in a minority (n=27). Miscarriage (42.5%) and termination (7.5%) accounted for half the pregnancy outcomes and the babies were born early (median 31.5 weeks) and small (median 1350 g). Maternal complications of bleeding, arrhythmia and heart failure were reported with no early maternal mortality. CONCLUSIONS In women with a Fontan circulation the fertility onset is delayed and pregnancy has a higher rate of miscarriage. Successful pregnancy resulted in small and premature babies. Significant maternal morbidity occurred. Whether pregnancy with its volume loading has an adverse effect on the long-term outcome of women with a single ventricle remains to be elucidated.

Can We Predict Sudden Cardiac Death in Long‐term Survivors of Atrial Switch Surgery for Transposition of the Great Arteries?

Objective This study aims to identify predictors of sudden cardiac death (SCD) in patients with transposition of the great arteries (TGA) who have undergone atrial baffle surgery with the Mustard or Senning operation. Background Patients with TGA and previous atrial baffle surgery are known to be at increased risk of SCD. Despite this, indications for insertion of an implantable cardiac defibrillator for primary prevention have not been established. Methods Eighty-nine patients with a diagnosis of TGA and previous Mustard or Senning repair were identified. Medical records were reviewed for SCD, aborted SCD, implantation of cardiac defibrillator (ICD), and use of cardiac medications. Clinically significant events (heart failure admissions, documented arrhythmias, and insertion of a pacemaker) were ascertained, and results of echocardiograms were explored. Results There were five SCDs in our population, and five patients underwent a primary prevention ICD insertion, with no subsequent sustained ventricular arrhythmia or aborted SCD. Patients who suffered SCD had undergone surgery at an older age (median 53 months vs. 14 months) in a slightly earlier era (median year of operation 1971 vs. 1975). Atrial arrhythmias requiring treatment were documented in 100% of the SCD and in 29% of the no SCD patients. Conclusions Criteria for insertion of primary prevention implantable cardiac defibrillators postatrial baffle surgery remain to be established. In the SCD subgroup, surgery at an older age, earlier era of surgical repair, and history of atrial arrhythmia appear to convey an increased risk of sudden death.OBJECTIVE This study aims to identify predictors of sudden cardiac death (SCD) in patients with transposition of the great arteries (TGA) who have undergone atrial baffle surgery with the Mustard or Senning operation. BACKGROUND Patients with TGA and previous atrial baffle surgery are known to be at increased risk of SCD. Despite this, indications for insertion of an implantable cardiac defibrillator for primary prevention have not been established. METHODS Eighty-nine patients with a diagnosis of TGA and previous Mustard or Senning repair were identified. Medical records were reviewed for SCD, aborted SCD, implantation of cardiac defibrillator (ICD), and use of cardiac medications. Clinically significant events (heart failure admissions, documented arrhythmias, and insertion of a pacemaker) were ascertained, and results of echocardiograms were explored. RESULTS There were five SCDs in our population, and five patients underwent a primary prevention ICD insertion, with no subsequent sustained ventricular arrhythmia or aborted SCD. Patients who suffered SCD had undergone surgery at an older age (median 53 months vs. 14 months) in a slightly earlier era (median year of operation 1971 vs. 1975). Atrial arrhythmias requiring treatment were documented in 100% of the SCD and in 29% of the no SCD patients. CONCLUSIONS Criteria for insertion of primary prevention implantable cardiac defibrillators postatrial baffle surgery remain to be established. In the SCD subgroup, surgery at an older age, earlier era of surgical repair, and history of atrial arrhythmia appear to convey an increased risk of sudden death.

Does Pregnancy Contribute to Systemic Right Ventricular Dysfunction in Adults with an Atrial Switch Operation

BACKGROUND To determine whether pregnancy might impact adversely on long-term outcomes in adults post an atrial switch repair on the background of data demonstrating an increased rate of heart failure and death in these adults with systemic right ventricles. METHODS We retrospectively analysed our adult population with an atrial switch repair for transposition of the great arteries to see whether any differences in outcomes (sudden cardiac death, heart failure admissions, use of heart failure medications) existed between women who had and women who had not undergone pregnancy. Controls from the remaining population (transposition of the great arteries and atrial switch operation women) were elected as long as their year of birth fell into the year of birth range seen in the patient group. RESULTS In women with transposition of the great arteries who have had an atrial switch repair, the long-term occurrence of sudden cardiac death and clinical heart failure (defined as a need for prescription of anti-failure medications or heart failure admissions) appears to be increased. CONCLUSION Pregnancy may have an adverse effect on long-term outcomes in women with systemic right ventricles.

Prospective evaluation of aortic stenosis in end-stage kidney disease: a more fulminant process?

BACKGROUND We have previously demonstrated an increased rate of progression of aortic stenosis (AS) in patients with end-stage kidney disease (CKD 5D) compared to controls. We sought to follow prospectively a CKD 5D cohort with AS and determine major event-free survival. Follow-up was terminated once all CKD 5D subjects had undergone aortic valve replacement (AVR) or died. Our aim was to determine whether the increased rate of progression resulted in shorter major event-free (AVR or death) survival as compared to controls. METHODS We re-matched our original CKD 5D cohort (n = 27) to a control cohort (n = 27) based on aortic valve area (AVA) at completion of the prior study. This was done as CKD 5D and AVA were the only statistically significant variables with respect to rate of progression. RESULTS All the CKD 5D patients (100%) underwent surgery or died during the follow-up period. In contrast, 17 (63%) of the controls underwent surgery or died. Of the remaining 10 controls, nine remain alive and free of AVR and one was lost to follow-up. CONCLUSION The controls displayed greater major event-free survival (P = 0.001), suggesting a need to consider patients with CKD 5D and AS for early AVR once echocardiographic evidence of moderate to severe AS is present, regardless of symptoms.

Mortality in adults with congenital heart disease

AIM Retrospective ascertainment of the causes of mortality in the adult congenital heart disease (ACHD) cohort of the Royal Melbourne Hospital (RMH). METHODS Deceased patients (n=73) of the 2519 ACHD patients in the Royal Melbourne Hospital registry (commenced in 1991) were identified. Retrospective analysis was undertaken. Age, gender of deceased individuals, and frequency and cause of death in different congenital diagnosis groups was explored. RESULTS Between 1991 and 2015, death occurred in 3.3% of the ACHD cohort. Median age at death was 32years (IQR 26-41.5) and 51% were male. The most frequent underlying cardiac conditions were Eisenmengers syndrome (22%), pulmonary atresia and ventricular septal defect+/-major aorto-pulmonary collateral arteries (12%), Tetralogy of Fallot (10%), transposition of great arteries (TGA) with intact ventricular septum (8%), single ventricle (8%) and congenitally corrected TGA (5%). The cause of death was available from medical records in 60 (82%) of the 73 patients. The majority of deaths were due to cardiac causes (67%) including sudden death (40%), heart failure (13%), and documented ventricular arrhythmias (8%). The most common non-cardiac cause of death was sepsis (10%). CONCLUSION The majority of deaths in this group were due to cardiac causes with sudden death and heart failure being the most common. Identification of risk factors for sudden death might assist identification of patients who may benefit from preventative therapies including implantable cardiac defibrillator.

Percutaneous closure of a giant saphenous vein graft aneurysm with an Amplatzer vascular plug.

A 67-year-old man with scleroderma was diagnosed with a giant (12.1 × 8.2 × 7.9 cm) saphenous vein graft (SVG) aneurysm while undergoing evaluation for dyspnea 15 years post-coronary artery bypass surgery. Computed tomography demonstrated the aneurysm to arise from the SVG supplying the second

The Cardiac Genetics Clinic: a model for multidisciplinary genomic medicine

Objectives: To describe patient characteristics, standard operating procedure, and uptake of genetic testing at the multidisciplinary Cardiac Genetics Clinic (CGC) at the Royal Melbourne Hospital during its first 6 years.