Berto J. Bouma

Preoperative Thresholds for Pulmonary Valve Replacement in Patients With Corrected Tetralogy of Fallot Using Cardiovascular Magnetic Resonance

Background— To facilitate the optimal timing of pulmonary valve replacement, we analyzed preoperative thresholds of right ventricular (RV) volumes above which no decrease or normalization of RV size takes place after surgery. Methods and Results— Between 1993 and 2006, 71 adult patients with corrected tetralogy of Fallot underwent pulmonary valve replacement in a nationwide, prospective follow-up study. Patients were evaluated with cardiovascular magnetic resonance both preoperatively and postoperatively. Changes in RV volumes were expressed as relative change from baseline. RV volumes decreased with a mean of 28%. RV ejection fraction did not change significantly after surgery (from 42±10% to 43±10%; P=0.34). Concomitant RV outflow tract reduction resulted in a 25% larger decrease of RV volumes. After correction for surgical RV outflow tract reduction, higher preoperative RV volumes (mL/m2) were independently associated with a larger decrease of RV volumes (RV end-diastolic volume: &bgr;=0.41; P<0.001). Receiver operating characteristic analysis revealed a cutoff value of 160 mL/m2 for normalization of RV end-diastolic volume or 82 mL/m2 for RV end-systolic volume. Conclusions— Overall, we could not find a threshold above which RV volumes did not decrease after surgery. Preoperative RV volumes were independently associated with RV remodeling and also when corrected for a surgical reduction of the RV outflow tract. However, normalization could be achieved when preoperative RV end-diastolic volume was <160 mL/m2 or RV end-systolic volume was <82 mL/m2.

The changing epidemiology of congenital heart disease

Congenital heart disease is the most common congenital disorder in newborns. Advances in cardiovascular medicine and surgery have enabled most patients to reach adulthood. Unfortunately, prolonged survival has been achieved at a cost, as many patients suffer late complications, of which heart failure and arrhythmias are the most prominent. Accordingly, these patients need frequent follow-up by physicians with specific knowledge in the field of congenital heart disease. However, planning of care for this population is difficult, because the number of patients currently living with congenital heart disease is difficult to measure. Birth prevalence estimates vary widely according to different studies, and survival rates have not been well recorded. Consequently, the prevalence of congenital heart disease is unclear, with estimates exceeding the number of patients currently seen in cardiology clinics. New developments continue to influence the size of the population of patients with congenital heart disease. Prenatal screening has led to increased rates of termination of pregnancy. Improved management of complications has changed the time and mode of death caused by congenital heart disease. Several genetic and environmental factors have been shown to be involved in the etiology of congenital heart disease, although this knowledge has not yet led to the implementation of preventative measures. In this Review, we give an overview of the etiology, birth prevalence, current prevalence, mortality, and complications of congenital heart disease.

Sudden Cardiac Death in Adult Congenital Heart Disease

Background— Sudden cardiac death (SCD) is a major cause of mortality in adults with congenital heart disease (CHD). The aim of this study was to determine the adult CHD population at risk of SCD and the clinical parameters associated with SCD. Methods and Results— We performed a multicenter case-control study. Patients who died suddenly as a result of proven or presumed arrhythmia were included (cases). For each case, 2 controls matched on diagnosis, type of surgical intervention, age, and gender were included. From 3 databases including 25 790 adults with CHD, 1189 deaths (5%) were identified, of whom 213 patients (19%) died suddenly. Arrhythmic death occurred in 171 of 1189 patients. The underlying cardiac lesions were mild, moderate, and severe CHD in 12%, 33%, and 55% of the SCD cases, respectively. Clinical variables associated with SCD were supraventricular tachycardia (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.5–7.9; P=0.004), moderate to severe systemic ventricular dysfunction (OR, 3.4; 95% CI, 1.1–10.4; P=0.034), moderate to severe subpulmonary ventricular dysfunction (OR, 3.4; 95% CI, 1.1–10.2; P=0.030), increased QRS duration (OR, 1.34 [per 10-ms increase]; 95% CI, 1.10–1.34; P=0.008), and QT dispersion (OR, 1.22 [per 10-ms increase]; 95% CI, 1.22–1.48; P=0.008). Conclusions— The clinical parameters found to be associated with SCD in adults with a broad spectrum of CHD, including systemic right ventricles, are similar to those in ischemic heart disease. Moreover, even those patients with mild cardiac lesions are potentially at risk for SCD. This highlights the need for further prospective studies as well as vigilant ongoing follow-up of the adult with CHD.

Factors associated with cardiac conduction disorders and permanent pacemaker implantation after percutaneous aortic valve implantation with the CoreValve prosthesis

BACKGROUND Cardiac conduction disorders and requirement for permanent pacemaker implantation (PPI) are not uncommon after surgical aortic valve replacement and have important clinical implications. We aimed to investigate the incidence of cardiac conduction disorders after percutaneous aortic valve implantation (PAVI) and to identify possible clinical factors associated with their development. METHODS We studied 34 patients (mean age 80 +/- 8 years, 18 male) who underwent PAVI with the CoreValve bioprosthesis (Corevalve Inc, Irvine, CA). Electrocardiographic evaluation was performed pre- and postprocedurally, and at 1-week and 1-month follow-up. Other clinical variables were obtained from the medical history, echocardiography, and angiography. RESULTS After PAVI, 7 patients required PPI, all of whom developed total atrioventricular block within 3 days postprocedurally. A smaller left ventricular outflow tract diameter (20.3 +/- 0.5 vs 21.6 +/- 1.8 cm, P = .01), more left-sided heart axis (-20 degrees +/- 29 degrees vs 19 degrees +/- 36 degrees , P = .02), more mitral annular calcification (10 +/- 1 vs 5 +/- 4 mm, P = .008), and a smaller postimplantation indexed effective orifice area (0.86 +/- 0.20 vs 1.10 +/- 0.26 cm(2)/m(2), P = .04) were associated with PPI. The incidence of new left bundle-branch block (LBBB) was 65% and was associated with a deeper implantation of the prosthesis: 10.2 +/- 2.3 mm in the new-LBBB group versus 7.7 +/- 3.1 mm in the non-LBBB group (P = .02). CONCLUSIONS Percutaneous aortic valve implantation with the CoreValve prosthesis results in a high incidence of total atrioventricular block requiring PPI and new-onset LBBB. Preexisting disturbance of cardiac conduction, a narrow left ventricular outflow tract, and the severity of mitral annular calcification predict the need for permanent pacing, whereas the only factor shown to be predictive for new-onset LBBB is the depth of prosthesis implantation.

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

BackgroundThe 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.MethodsTwenty-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.ResultsThe 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).ConclusionThe 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.

The prevalence of adult congenital heart disease, results from a systematic review and evidence based calculation.

PURPOSE The prevalence of adult patients with congenital heart disease (CHD) has been reported with a high degree of variability. Prevalence estimates have been calculated using birth rate, birth prevalence, and assumed survival and derived from large administrative databases. To report more robust prevalence estimate, we performed a systematic review for studies concerning CHD prevalence in adults. Moreover, to diminish bias of calculated estimates, we conducted an evidence-based calculation for the Netherlands. METHODS A systematic database search was performed to identify reports on the prevalence of adult CHD. Bicuspid aortic valve, mitral valve prolapse, Marfan syndrome, cardiomyopathy, congenital arrhythmia, and spontaneously closed defects were excluded. In addition, CHD prevalence was calculated using birth rate, birth prevalence, and survival estimates. RESULTS Our search yielded 10 publications on the prevalence of CHD in adults. Four reported results from population wide cross-sectional data, whereas in 6, prevalence was calculated. Mean prevalence reported by empirical studies was 3,562 per million when unspecified lesions were included and 2,297 per million when these were excluded. Mean prevalence derived from calculation was 3,536. Our calculated estimate was 3,228 per million adults. Taking these estimates as well as the limitations inherent to their derivation into consideration, the prevalence of CHD in the adult population is approximately 3,000 per million adults. CONCLUSION This systematic review presents a comprehensive overview of publications on the prevalence of CHD in adults. The best available evidence suggests that overall prevalence of CHD in the adult population is in the region of 3,000 per million.

Effect of Valsartan on Systemic Right Ventricular Function A Double-Blind, Randomized, Placebo-Controlled Pilot Trial

Background— The role of angiotensin II receptor blockers in patients with a systemic right ventricle has not been elucidated. Methods and Results— We conducted a multicenter, double-blind, parallel, randomized controlled trial of angiotensin II receptor blocker valsartan 160 mg twice daily compared with placebo in patients with a systemic right ventricle caused by congenitally or surgically corrected transposition of the great arteries. The primary end point was change in right ventricular ejection fraction during 3-year follow-up, determined by cardiovascular magnetic resonance imaging or, in patients with contraindication for magnetic resonance imaging, multirow detector computed tomography. Secondary end points were change in right ventricular volumes and mass, ![Graphic][1] peak, and quality of life. Primary analyses were performed on an intention-to-treat basis. A total of 88 patients (valsartan, n=44; placebo, n=44) were enrolled in the trial. No serious adverse effects occurred in either group. There was no significant effect of 3-year valsartan therapy on systemic right ventricular ejection fraction (treatment effect, 1.3%; 95% confidence interval, −1.3% to 3.9%; P =0.34), maximum exercise capacity, or quality of life. There was a larger increase in right ventricular end-diastolic volume (15 mL; 95% confidence interval, 3–28 mL; P <0.01) and mass (8 g; 95% confidence interval, 2–14 g; P =0.01) in the placebo group than in the valsartan group. Conclusions— There was no significant treatment effect of valsartan on right ventricular ejection fraction, exercise capacity, or quality of life. Valsartan was associated with a similar frequency of significant clinical events as placebo. Small but significant differences between valsartan and placebo were present for change in right ventricular volumes and mass. Clinical Trial Registration— URL: . Unique identifier: [ISRCTN52352170][2]. # Clinical Perspective {#article-title-47} [1]: /embed/inline-graphic-1.gif [2]: /external-ref?link_type=ISRCTN&access_num=ISRCTN52352170Background— The role of angiotensin II receptor blockers in patients with a systemic right ventricle has not been elucidated. Methods and Results— We conducted a multicenter, double-blind, parallel, randomized controlled trial of angiotensin II receptor blocker valsartan 160 mg twice daily compared with placebo in patients with a systemic right ventricle caused by congenitally or surgically corrected transposition of the great arteries. The primary end point was change in right ventricular ejection fraction during 3-year follow-up, determined by cardiovascular magnetic resonance imaging or, in patients with contraindication for magnetic resonance imaging, multirow detector computed tomography. Secondary end points were change in right ventricular volumes and mass, peak, and quality of life. Primary analyses were performed on an intention-to-treat basis. A total of 88 patients (valsartan, n=44; placebo, n=44) were enrolled in the trial. No serious adverse effects occurred in either group. There was no significant effect of 3-year valsartan therapy on systemic right ventricular ejection fraction (treatment effect, 1.3%; 95% confidence interval, −1.3% to 3.9%; P=0.34), maximum exercise capacity, or quality of life. There was a larger increase in right ventricular end-diastolic volume (15 mL; 95% confidence interval, 3–28 mL; P<0.01) and mass (8 g; 95% confidence interval, 2–14 g; P=0.01) in the placebo group than in the valsartan group. Conclusions— There was no significant treatment effect of valsartan on right ventricular ejection fraction, exercise capacity, or quality of life. Valsartan was associated with a similar frequency of significant clinical events as placebo. Small but significant differences between valsartan and placebo were present for change in right ventricular volumes and mass. Clinical Trial Registration— URL: http://www.controlled-trials.com. Unique identifier: ISRCTN52352170.

Beyond the root: dilatation of the distal aorta in Marfan’s syndrome

Objective: To investigate dilatory changes of the aorta distal to the root in patients with Marfan’s syndrome. Methods and results: Data of 268 patients with Marfan’s syndrome who were enrolled in the Euro Heart Survey on adult congenital heart disease were analysed. Data used for this study were baseline characteristics, diameters at four levels of the aorta and events during follow up (dissection, aortic repairs and death). At inclusion, 26 patients had a previous dissection and 53 patients without a previous dissection had undergone elective aortic repair, thus leaving 189 patients without previous dissection or repair. During follow up (median 5.4 years), four patients died. A total of 46 aortic events (dissection or elective surgery) occurred in 45 patients, in the distal aorta in 14 patients (31%). Baseline aortic diameter at the levels distal to the root (arch, descending aorta and abdominal aorta) was greater in patients with than in those without a previous elective aortic root intervention (median 26 mm v 24 mm, p  =  0.01; 25 mm v 20 mm, p < 0.01; and 20 mm v 17 mm, p < 0.01, respectively). Multivariate analysis showed that a previous elective aortic intervention was associated with a fourfold increased probability of dilatation of the distal aorta, after adjustment for age and sex (p < 0.01). In patients without a previous intervention, the baseline diameter of the descending aorta was an independent predictor of aortic events (hazard ratio 3.0 per quartile, 95% CI 1.5 to 5.9, p  =  0.002). Cause for concern is that complete measurements of the aorta (at least one measurement at each level at baseline or during follow up) were available for only 38% of the patients. Conclusions: Almost one in every three aortic events occurring during follow up of these patients involved the distal aorta. After elective aortic root replacement, a dilated distal aorta is more common than before. Moreover, an increased diameter of the descending aorta is associated with a higher risk of aortic events in patients without previous dissection or aortic root replacement, independent of the diameter of the aortic root. Careful monitoring of the entire aorta is essential for the optimal management of patients with Marfan’s syndrome, especially after elective surgery, but is insufficiently performed in Europe.

Gender and Outcome in Adult Congenital Heart Disease

Background— Gender differences in prognosis have frequently been reported in cardiovascular disease but less so in congenital heart disease. We investigated whether gender is associated with outcome in adult patients with congenital heart disease. Methods and Results— From the CONgenital CORvitia (CONCOR) national registry for adults with congenital heart disease, 7414 patients were identified. All outcomes before entry into the registry and during subsequent follow-up were recorded, and differences between men and women were analyzed with the underlying congenital heart defect taken into account. Median age at the end of follow-up was 35 years (range, 17 to 91 years); 49.8% were female. No gender difference in mortality was found. Women had a 33% higher risk of pulmonary hypertension (odds ratio [OR]=1.33; 95% CI, 1.07 to 1.65; P=0.01), a 33% lower risk of aortic outcomes (OR=0.67; 95% CI, 0.50 to 0.90; P=0.007), a 47% lower risk of endocarditis (OR=0.53; 95% CI, 0.40 to 0.70; P<0.001), and a 55% lower risk of an implantable cardioverter-defibrillator (OR=0.45; 95% CI, 0.26 to 0.80; P=0.006). Furthermore, the risk of arrhythmias appeared to be lower in women (OR=0.88; 95% CI, 0.77 to 1.02; P=0.08). Conclusions— The risk of several major cardiac outcomes in adult patients with congenital heart disease appears to vary by gender.

Right Ventricular Failure Following Chronic Pressure Overload Is Associated With Reduction in Left Ventricular Mass : Evidence for Atrophic Remodeling

OBJECTIVES We sought to study whether patients with right ventricular failure (RVF) secondary to chronic thromboembolic pulmonary hypertension (CTEPH) have reduced left ventricular (LV) mass, and whether LV mass reduction is caused by atrophy. BACKGROUND The LV in patients with CTEPH is underfilled (unloaded). LV unloading may cause atrophic remodeling that is associated with diastolic and systolic dysfunction. METHODS We studied LV mass using cardiac magnetic resonance imaging (MRI) in 36 consecutive CTEPH patients (before/after pulmonary endarterectomy [PEA]) and 11 healthy volunteers selected to match age and sex of patients. We studied whether LV atrophy is present in monocrotaline (MCT)-injected rats with RVF or controls by measuring myocyte dimensions and performing in situ hybridization. RESULTS At baseline, CTEPH patients with RVF had significantly lower LV free wall mass indexes than patients without RVF (35 ± 6 g/m(2) vs. 44 ± 7 g/m(2), p = 0.007) or volunteers (42 ± 6 g/m(2), p = 0.006). After PEA, LV free wall mass index increased (from 38 ± 6 g/m(2) to 44 ± 9 g/m(2), p = 0.001), as right ventricular (RV) ejection fraction improved (from 31 ± 8% to 56 ± 12%, p < 0.001). Compared with controls, rats with RVF had reduced LV free wall mass and smaller LV free wall myocytes. Expression of atrial natriuretic peptide was higher, whereas that of α-myosin heavy chain and sarcoplasmic reticulum calcium ATPase-2 were lower in RVF than in controls, both in RV and LV. CONCLUSIONS RVF in patients with CTEPH is associated with reversible reduction in LV free wall mass. In a rat model of RVF, myocyte shrinkage due to atrophic remodeling contributed to reduction in LV free wall mass.