Outcomes following the implantation of cardioverter-defibrillator for primary prevention in transposition of the great arteries after intra-atrial baffle repair: a single-centre experience.

AIMS: Patients with D-loop transposition of the great arteries (D-TGA) status post intra-atrial baffling are at an increased risk for sudden cardiac arrest. The benefit of primary implantable cardioverter-defibrillator (ICD) implantation in these patients is questionable due to high burden of adverse events. We aimed to evaluate the incidence and causes of all types of device shocks, as well as of device-related complications among patients with D-TGA implanted with ICDs for primary prevention. METHODS AND RESULTS: Retrospective analysis of all patients with D-TGA who underwent atrial switch procedure and ICD implantation for primary prevention. Eighteen patients (83% males) were identified. Average age at atrial switch was 2.5 years (range 0.1-17) and at ICD implantation 26 years (15-41). During a median follow-up of 4 years, 10 patients (55%) received shocks for non-ventricular arrhythmic events, whereas 1 patient was shocked for ventricular tachycardia, for an annual rate of shock delivery of 7.1%. The most common cause for shock delivery was the occurrence of atrial arrhythmias, mostly in the form of atrial flutter. Elevated systemic ventricular end-diastolic pressures were found to be associated with an increased risk for inappropriate shocks. Five patients (28%) required lead extraction and three required generator change due to device recalls during follow-up. CONCLUSION: Atrial arrhythmias were the most common cause for ICD shocks in a primary prevention population, while ventricular tachycardia was infrequent. The association between elevated end-diastolic pressures and the occurrence of arrhythmias demonstrates the close mechano-electrical relationship in D-TGA and may be an important predictor of arrhythmic events.

Accuracy of Imaging Modalities in Detection of Baffle Leaks in Patients Following Atrial Switch Operation.

AIMS: Patients with dextro-transposition of the great arteries (d-TGA) status post atrial switch operation are vulnerable to complications such as baffle leaks. The best noninvasive imaging modality to detect baffle leaks is unknown. The purpose of this study was to determine the sensitivity and specificity of different noninvasive imaging modalities in the detection of baffle leaks in this population. METHODS AND RESULTS: A single center retrospective chart review of atrial switch patients was performed. Sensitivity, specificity, negative predictive value, and positive predictive value for detecting leaks were calculated for transthoracic echocardiogram (TTE) with and without agitated saline, transesophageal echocardiogram (TEE) with and without agitated saline, and cardiac magnetic resonance imaging (cMRI). Studies were included if performed within 1 year of catheterization. Angiography via catheterization was used as the gold standard for the detection of baffle leaks. Fifty-eight atrial switch patients (54 Mustards: four Sennings) from a single pediatric center, undergoing 76 catheterizations, were analyzed. Thirty-nine catheterizations documented a baffle leak. Overall combination of sensitivity and specificity was better in agitated saline studies (TTE: sensitivity 71.4%, specificity 100%; TEE: sensitivity 100%, specificity 92.3%) versus nonagitated studies (TTE: sensitivity 50.0%, specificity 100%; TEE: sensitivity 83.3%, specificity 77.8%; or cMRI: sensitivity 66.7%, specificity 100%). CONCLUSION: TTE or TEE with agitated saline is superior to cardiac magnetic resonance imaging or nonagitated saline TTE and TEE in detecting baffle leaks in atrial switch patients. Agitated saline studies should be performed in this population when looking for baffle leaks.

Assessment of coronary artery calcium using dual-energy subtraction digital radiography.

Cardiovascular disease is the leading cause of global mortality, yet its early detection remains a vexing problem of modern medicine. Although the computed tomography (CT) calcium score predicts cardiovascular risk, relatively high cost ($250-400) and radiation dose (1-3 mSv) limit its universal utility as a screening tool. Dual-energy digital subtraction radiography (DE; <$60, 0.07 mSv) enables detection of calcified structures with high sensitivity. In this pilot study, we examined DE radiography's ability to quantify coronary artery calcification (CAC). We identified 25 patients who underwent non-contrast CT and DE chest imaging performed within 12 months using documented CAC as the major inclusion criteria. A DE calcium score was developed based on pixel intensity multiplied by the area of the calcified plaque. DE scores were plotted against CT scores. Subsequently, a validation cohort of 14 additional patients was independently evaluated to confirm the accuracy and precision of CAC quantification, yielding a total of 39 subjects. Among all subjects (n = 39), the DE score demonstrated a correlation coefficient of 0.87 (p < 0.0001) when compared with the CT score. For the 13 patients with CT scores of <400, the correlation coefficient was -0.26. For the 26 patients with CT scores of ≥400, the correlation coefficient yielded 0.86. This pilot study demonstrates the feasibility of DE radiography to identify patients at the highest cardiovascular risk. DE radiography's accuracy at lower scores remains unclear. Further evaluation of DE radiography as an inexpensive and low-radiation imaging tool to diagnose cardiovascular disease appears warranted.

Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: results of a two-year open-label extension trial.

BACKGROUND: Cardiomyopathy is a leading cause of morbidity and mortality in boys with Duchenne muscular dystrophy (DMD). We recently showed in a 12-month double-blind randomized controlled trial that adding eplerenone to background medical therapy was cardioprotective in this population. The objective of this study was to evaluate the safety and efficacy of longer-term eplerenone therapy in boys with DMD. RESULTS: Eleven subjects (phase 1 baseline median [range] age: 13 [7 - 25] years) from the original 12-month trial at a single participating center were enrolled. Importantly, those who entered the extension study who had been on eplerenone previously were significantly older than those who had originally been on placebo (median age 10.5 vs. 18.0 years, p = 0.045). During an additional 24-month open-label extension study, all boys received eplerenone 25 mg orally once daily to treat preclinical DMD cardiomyopathy, defined as evident myocardial damage by late gadolinium enhancement cardiac magnetic resonance (LGE) with preserved ejection fraction (EF). The threshold for potassium level, the primary safety measure, was not exceeded in any non-hemolyzed blood sample. Over 24 months, left ventricular (LV) systolic strain, a more sensitive marker whose more negative values indicate greater contractility significantly improved (median change -4.4%, IQR -5.8 to -0.9%) in younger subjects whereas older subjects' strain remained stable without significant worsening or improvement (median change 0.2%, IQR -1.1 to 4.3%). EF and extent of myocardial damage by LGE remained stable in both groups over 2 years. CONCLUSIONS: Eplerenone offers effective and safe cardioprotection for boys with DMD, particularly when started at a younger age. Eplerenone is a useful clinical therapeutic option, particularly if treatment is initiated earlier in life when cardiac damage is minimal. TRIAL REGISTRATION: http://ClinicalTrials.gov identifier NCT01521546. Registered 26 January 2012.

Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Cardiomyopathy is a leading cause of death in patients with Duchenne muscular dystrophy and myocardial damage precedes decline in left ventricular systolic function. We tested the efficacy of eplerenone on top of background therapy in patients with Duchenne muscular dystrophy with early myocardial disease. METHODS: In this randomised, double-blind, placebo-controlled trial, boys from three centres in the USA aged 7 years or older with Duchenne muscular dystrophy, myocardial damage by late gadolinium enhancement cardiac MRI and preserved ejection fraction received either eplerenone 25 mg or placebo orally, every other day for the first month and once daily thereafter, in addition to background clinician-directed therapy with either angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Computer-generated randomisation was done centrally using block sizes of four and six, and only the study statistician and the investigational pharmacy had the preset randomisation assignments. The primary outcome was change in left ventricular circumferential strain (Ecc) at 12 months, a measure of contractile dysfunction. Safety was established through serial serum potassium levels and measurement of cystatin C, a non-creatinine measure of kidney function. This trial is registered with ClinicalTrials.gov, number NCT01521546. FINDINGS: Between Jan 26, 2012, and July 3, 2013, 188 boys were screened and 42 were enrolled. 20 were randomly assigned to receive eplerenone and 22 to receive placebo, of whom 20 in the eplerenone group and 20 in the placebo group completed baseline, 6-month, and 12-month visits. After 12 months, decline in left ventricular circumferential strain was less in those who received eplerenone than in those who received placebo (median ΔEcc 1·0 [IQR 0·3-2·2] vs 2·2 [1·3-3·1]; p=0·020). Cystatin C concentrations remained normal in both groups, and all non-haemolysed blood samples showed normal potassium concentrations. One 23-year-old patient in the placebo group died of fat embolism, and another patient in the placebo group withdrew from the trial to address long-standing digestive issues. All other adverse events were mild: short-lived headaches coincident with seasonal allergies occurred in one patient given eplerenone, flushing occurred in one patient given placebo, and anxiety occurred in another patient given placebo. INTERPRETATION: In boys with Duchenne muscular dystrophy and preserved ejection fraction, addition of eplerenone to background ACEI or ARB therapy attenuates the progressive decline in left ventricular systolic function. Early use of available drugs warrants consideration in this population at high risk of cardiac death, but further studies are needed to determine the effect of combination cardioprotective therapy on event-free survival in Duchenne muscular dystrophy. FUNDING: BallouSkies, Parent Project for Muscular Dystrophy, US National Center for Advancing Translational Sciences, and US National Institutes of Health.

Major adverse maternal cardiovascular-related events in those with aortopathies. What should we expect?

Major adverse maternal cardiovascular-related events (MAMCRE) in aortopathy patients undergoing pregnancy are poorly defined. The aim was to assess for MAMCRE in pregnant patients with aortopathy or aortic enlargement in conotruncal defects (CTD), and determine if there are differences between groups. We conducted a single-center retrospective review of pregnant women (2000-2013) with hereditary vascular disease (HVD: BAV, COA), heritable fibrillinopathies (HF: MFS, EDS, LDS, FTAAS), and CTD with aortic dilatation (TOF, d-TGA, DORV). MAMCRE included: aortic dissection/surgery, therapeutic abortion, change in mode of delivery, and aortic growth > 0.5 cm within 1 year. We identified 73 patients/97 pregnancies (39/50 HVD, 15/20 HF, and 19/27 CTD). There were 14 MAMCRE (14%); 85% (n = 12) occurred in HV and HF patients and was associated with higher baseline cross-sectional-to-height (CSA/Ht) ratio (6.6 [Symbol: see text] 2.5 vs. 5.1 [Symbol: see text] 1.3, p = 0.005). There was more aortic surgery in the HF (vs. HV) (RR 3.9, p = 0.12). Only 2 MAMCRE (aortic growth) occurred in CTD. Overall and emergent C-section was higher than the general population (52% vs. 29%, p < 0.001 and 16% vs. 3%, p < 0.001) as was postpartum hemorrhage (PPH) (6% vs. 1.5%, p < 0.001). We describe the largest series of pregnant women with aortopathy and found a substantial incidence of MAMCRE, which was associated with higher pre-pregnancy CSA/Ht ratio. Rates of C-section and PPH were higher than the general population. Our data suggest that larger, multi-center studies are needed to define risks that predict MAMCRE/obstetric events in women with aortopathies, allowing optimal medical care during pregnancy.