Effect of age on exercise capacity and cardiac reserve in patients with pulmonary atresia with intact ventricular septum after biventricular repair

OBJECTIVESIn patients with pulmonary atresia with intact ventricular septum (PAIVS), biventricular repair is considered to be the optimal treatment option in the absence of significant right ventricular (RV) hypoplasia. However, long-term clinical outcome studies are limited. We evaluated exercise capacity and cardiac function during pharmacological stress in children and young adults with PAIVS after biventricular repair.METHODSTen PAIVS patients after biventricular repair, with a median age of 12 years (range 9-42 years), underwent a cardiopulmonary exercise test, dobutamine stress magnetic resonance imaging (DS-MRI) and delayed contrast enhancement (DCE) MRI.RESULTSThe patients' ages negatively correlated with exercise capacity (r = -0.72, P = 0.01) as well as left (LV) and RV stroke volume (SV) response to pharmacological stress (r = -0.72, P = 0.02; and r = -0.64, P = 0.04; respectively), Furthermore, older age was associated with decreased RV E/A volume ratio and increased pulmonary late diastolic forward flow percentage (r = 0-0.65, P = 0.04, r = 0.66, P = 0.03, respectively). RV E/A volume ratio positively correlated with RV-SV response to DS-MRI (r = 0.77, P = 0.009). and O(2)-pulse during physical stress correlated with biventricular SV response to DS-MRI. No RV or LV ventricular myocardial fibrosis was detected.CONCLUSIONSIn PAIVS patients after biventricular repair exercise capacity and cardiac reserve decrease with age. These findings appear to be related to impaired diastolic RV function and decreased RV filling, indicating that the function of the relatively small RV deteriorates with tim

One frame and several new infinite families of Z-cyclic whist designs

AbstractIn 2001, Ge and Zhu published a frame construction which they utilized to construct a large class of Z-cyclic triplewhist designs. In this study the power and elegance of their methodology is illustrated in a rather dramatic fashion. Primarily due to the discovery of a single new frame it is possible to combine their techniques with the product theorems of Anderson, Finizio and Leonard along with a few new specific designs to obtain several new infinite classes of Z-cyclic whist designs. A sampling of the new results contained herein is as follows: (1) Z-cyclic Wh(33p+1), p a prime of the form 4t+1; (2) Z-cyclic Wh(32n+1s+1), for all n⩾1, s=5,13,17; (3) Z-cyclic Wh(32ns+1), for all n⩾1, s=35,55,91; (4) Z-cyclic Wh(32n+1s), for all n⩾1, and for all s for which there exist a Z-cyclic Wh(3s) and a homogeneous (s,4,1)-DM; and (5) Z-cyclic Wh(32ns) for all n⩾1, s=5,13. Many other results are also obtained. In particular, there exist Z-cyclic Wh(33v+1) where v is any number for which Ge and Zhu obtained Z-cyclic TWh(3v+1)

Aortic distensibility in Marfan syndrome:a potential predictor of aortic events?

Contains fulltext : 239962.pdf (Publisher’s version ) (Open Access

Genome-wide methylation patterns in Marfan syndrome

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The role of cystatin C as a biomarker for prognosis in pulmonary arterial hypertension due to congenital heart disease

AbstractBackgroundAdults with pulmonary arterial hypertension due to congenital heart disease (PAH-CHD) have a poor prognosis. Identifying patients with a high risk for clinical events and death is important because their prognosis can be improved by intensifying their treatment. Cystatin C, a novel cardiac biomarker, correlates with right ventricular dimensions in patients with idiopathic PAH, giving it potential to determine prognosis in PAH-CHD patients. We investigated the predictive value of cystatin C for long-term mortality and clinical events.MethodsFifty-nine PAH-CHD patients (mean age 42 SD 13 years, 42% male) were included in this prospective observational study, with cystatin C measurements between 2005 and 2015 on the outpatient clinic. Patients were evaluated with a standardized evaluation protocol including laboratory, functional and echocardiographic variables. Clinical events comprised worsening functional classification, worsening heart failure, symptomatic hyperviscosity, haemoptysis and arrhythmia. We used Cox regression to determine predictors for mortality and clinical events.ResultsMean follow-up was 4.4years, during which 12 (20%) patients died. Cystatin C (HR 1.3, p<0.001), creatinine (HR 1.2, p<0.001), NT-pro-BNP (HR 2.0, p=0.012), hs-troponin T (HR 1.9, p=0.005), 6-MWD (HR 0.8, p=0.044) and TAPSE (HR 0.8, p<0.001) predicted mortality. Similar results were found for the prediction of clinical events. When adjusted for NT-pro-BNP or glomerular filtration rate in multivariate analysis, cystatin C remained predictive for mortality.ConclusionsCystatin C, a novel cardiac biomarker, predicts long-term mortality and clinical events in patients with PAH-CHD. Consequently, cystatin C may attribute to clinical decision making regarding treatment intensity

Evaluating the systemic right ventricle by CMR: the importance of consistent and reproducible delineation of the cavity

Contains fulltext : 70334.pdf (publisher's version ) (Open Access)BACKGROUND: The method used to delineate the boundary of the right ventricle (RV), relative to the trabeculations and papillary muscles in cardiovascular magnetic resonance (CMR) ventricular volume analysis, may matter more when these structures are hypertrophied than in individuals with normal cardiovascular anatomy. This study aimed to compare two methods of cavity delineation in patients with systemic RV. METHODS: Twenty-nine patients (mean age 34.7 +/- 12.4 years) with a systemic RV (12 with congenitally corrected transposition of the great arteries (ccTGA) and 17 with atrially switched (TGA) underwent CMR. We compared measurements of systemic RV volumes and function using two analysis protocols. The RV trabeculations and papillary muscles were either included in the calculated blood volume, the boundary drawn immediately within the apparently compacted myocardial layer, or they were manually outlined and excluded. RV stroke volume (SV) calculated using each method was compared with corresponding left ventricular (LV) SV. Additionally, we compared the differences in analysis time, and in intra- and inter-observer variability between the two methods. Paired samples t-test was used to test for differences in volumes, function and analysis time between the two methods. Differences in intra- and inter-observer reproducibility were tested using an extension of the Bland-Altman method. RESULTS: The inclusion of trabeculations and papillary muscles in the ventricular volume resulted in higher values for systemic RV end diastolic volume (mean difference 28.7 +/- 10.6 ml, p < 0.001) and for end systolic volume (mean difference 31.0 +/- 11.5 ml, p < 0.001). Values for ejection fraction were significantly lower (mean difference -7.4 +/- 3.9%, p < 0.001) if structures were included. LV SV did not differ significantly from RV SV for both analysis methods (p = NS). Including structures resulted in shorter analysis time (p < 0.001), and showed better inter-observer reproducibility for ejection fraction (p < 0.01). CONCLUSION: The choice of method for systemic RV cavity delineation significantly affected volume measurements, given the CMR acquisition and analysis systems used. We recommend delineation outside the trabeculations for routine clinical measurements of systemic RV volumes as this approach took less time and gave more reproducible measurements

Long-term clinical outcomes of losartan in patients with Marfan syndrome:follow-up of the multicentre randomized controlled COMPARE trial

AIMS: The COMPARE trial showed a small but significant beneficial effect of 3-year losartan treatment on aortic root dilatation rate in adults with Marfan syndrome (MFS). However, no significant effect was found on clinical endpoints, possibly due to a short follow-up period. The aim of the current study was therefore to investigate the long-term clinical outcomes after losartan treatment. METHODS AND RESULTS: In the original COMPARE study (inclusion 2008-2009), adult patients with MFS (n = 233) were randomly allocated to either the angiotensin-II receptor blocker losartan® on top of regular treatment (β-blockers in 71% of the patients) or no additional medication. After the COMPARE trial period of 3 years, study subjects chose to continue their losartan medication or not. In a median follow-up period of 8 years, 75 patients continued losartan medication, whereas 78 patients, originally allocated to the control group, never used losartan after inclusion. No differences existed between baseline characteristics of the two groups except for age at inclusion [losartan 34 (interquartile range, IQR 26-43) years, control 41 (IQR 30-52) years; P = 0.031], and β-blocker use (losartan 81%, control 64%; P = 0.022). A pathological FBN1 mutation was present in 76% of patients and 58% of the patients were male. Clinical endpoints, defined as all-cause mortality, aortic dissection/rupture, elective aortic root replacement, reoperation, and vascular graft implantation beyond the aortic root, were compared between the two groups. A per-patient composite endpoint was also analysed. Five deaths, 14 aortic dissections, 23 aortic root replacements, 3 reoperations, and 3 vascular graft implantations beyond the aortic root occurred during follow-up. Except for aortic root replacement, all endpoints occurred in patients with an operated aortic root. Patients who used losartan during the entire follow-up period showed a reduced number of events compared to the control group (death: 0 vs. 5, P = 0.014; aortic dissection: 3 vs. 11, P = 0.013; elective aortic root replacement: 10 vs. 13, P = 0.264; reoperation: 1 vs. 2, P = 0.463; vascular graft implantations beyond the aortic root 0 vs. 3, P = 0.071; and composite endpoint: 14 vs. 26, P = 0.019). These results remained similar when corrected for age and β-blocker use in a multivariate analysis. CONCLUSION: These results suggest a clinical benefit of combined losartan and β-blocker treatment in patients with MFS