Sinus Valsalva Aneurysm of the non-coronary cusp initially diagnosed as right ventricular thrombus: A case report.

Sinus of Valsalva aneurysms are abnormal bulges of the aortic root caused by a tissue deficiency resulting in an enlargement of the aortic root in the area between the aortic annulus and the sinotubular junction. Frequently, sinus of Valsalva aneurysms are asymptomatic. However, sinus of Valsalva aneurysms can also be potentially fatal due to their risk of rupture. We present a case of a 49-year old asymptomatic male patient with a rare image of a sinus of Valsalva aneurysm of the non-coronary cusp which was initially mistaken for a right ventricular thrombus. Surgical repair of the sinus of Valsalva aneurysm was eventually achieved by a valve sparing root replacement and the patient was discharged 7 days after surgery. This case report shows that sinus of Valsalva aneurysms are vulnerable to misdiagnosis when it is not initially suspected. Because of the potential fatality of this phenomenon we would like to underline the necessary vigilance in the diagnostic process, as sinus of Valsalva aneurysms can be missed when the physician is not aware of this potential rare diagnosis.

Myocardial Deformation in the Systemic Right Ventricle: Strain Imaging Improves Prediction of the Failing Heart.

BACKGROUND: Predicting heart failure events in patients with a systemic right ventricle (sRV) due to transposition of the great arteries (TGA) is important for timely intensification of follow-up. This study assessed the value of strain compared with currently used parameters as predictor for heart failure-free survival in patients with sRV. METHODS: In participants of a multicentre trial, speckle-tracking echocardiography (STE) was performed to assess global longitudinal strain (GLS), mechanical dispersion (MD), and postsystolic shortening (PSS). Cox regression was used to determine the association of STE parameters with the combined end point of progression of heart failure and death, compared with cardiovascular magnetic resonance (CMR) and computed tomography (CT) derived parameters. RESULTS: Echocardiograms of 60 patients were analyzed (mean age 34 ± 11 years, 65% male, 35% congenitally corrected TGA). Mean GLS was -13.5 ± 2.9%, median MD was 49 (interquartile range [IQR] 30-76) ms, and 14 patients (23%) had PSS. During a median 8 (IQR 7-9) years, 15 patients (25%) met the end point. GLS, MD, and PSS were all associated with heart failure-free survival in univariable analysis. After correction for age, only GLS (optimal cutoff > -10.5%) and CMR/CT-derived sRV ejection fraction (optimal cutoff < 30%) remained associated with heart failure-free survival: hazard ratio (HR) 8.27, 95% confidence interval (CI) 2.50-27.41 (P < 0.001), and HR 4.34, 95% CI 1.48-12.74 (P = 0.007), respectively). Combining GLS and ejection fraction improved prediction, with patients with both GLS > -10.5% and sRV ejection fraction < 30% at highest risk (HR 19.69, 95% CI 4.90-79.13; P < 0.001). CONCLUSIONS: The predictive value of GLS was similar to that of CMR/CT-derived ejection fraction. The combination of GLS and ejection fraction identified patients at highest risk of heart failure and death. Easily available STE parameters can be used to guide follow-up intensity and can be integrated into future risk prediction scores.

Progression of aortic root dilatation and aortic valve regurgitation after the arterial switch operation.

OBJECTIVE: To study neo-aortic growth and the evolution of neo-aortic valve regurgitation (AR) in patients with transposition of the great arteries (TGA) after arterial switch operation (ASO) from newborn to adulthood and to identify patients at risk. METHODS: Neo-aortic dimensions (annulus/root/sinotubular junction) and neo-aortic valve regurgitation were assessed serially in 345 patients with TGA who underwent ASO between 1977 and 2015. Linear mixed-effect models were used to assess increase of neo-aortic dimensions over time and to identify risk factors for dilatation. Risk factor analysis for AR by using time-dependent Cox regression models. RESULTS: After a rapid increase in the first year after ASO and proportional growth in childhood, neo-aortic dimensions continue to increase in adulthood without stabilisation. Annual diameter increase in adulthood was 0.39±0.06, 0.63±0.09 and 0.54±0.11 mm for, respectively, neo-aortic annulus, root and sinotubular junction, all significantly exceeding normal growth. AR continues to develop over time: freedom from AR ≥moderate during the first 25 years post-ASO was 69%. Risk factors for root dilatation were complex TGA anatomy (TGA-ventricular septal defect (VSD), double outlet right ventricle with subpulmonary VSD) and male gender. Risk factors for AR ≥moderate were: complex TGA anatomy and neo-aortic growth. Per millimetre increase in aortic root dimension, there was a 9% increase in the hazard of AR ≥moderate. Bicuspid pulmonary valve did not relate to the presence of root dilatation or AR. CONCLUSION: After ASO, neo-aortic dilatation proceeds beyond childhood and is associated with an increase in AR incidence over time. Careful follow-up of the neo-aortic valve and root function is mandatory, especially in males and in patients with complex TGA anatomy.

Long-term clinical outcomes of valsartan in patients with a systemic right ventricle: Follow-up of a multicenter randomized controlled trial.

OBJECTIVES: In the VAL-SERVE (Valsartan in Systemic Right Ventricle) trial, three-year valsartan treatment improved systemic ventricular function only in symptomatic patients with congenitally or with an atrial switch corrected transposition of the great arteries. The aim of the current study was to investigate the longer-term clinical outcomes after valsartan treatment. METHODS: From 2006 to 2009, 88 adults were randomly allocated 1:1 to either valsartan or placebo for three consecutive years. Endpoints were defined as overall survival and freedom from clinical events (arrhythmia, heart failure, tricuspid valve surgery, death). RESULTS: Cardiac drug use and median follow-up after trial close-out (8.3 years) was similar between the randomization groups. Six patients (valsartan n = 3, placebo n = 3) died in 364 and 365 person-years (P = 0.999). No difference in the composite or separate clinical endpoints was found between the randomization groups, with corresponding long-term event-free survival rates of 50% and 34%. Nevertheless, in symptomatic patients valsartan significantly reduced the risk for events compared to placebo (HR 0.37, 95% CI 0.17-0.92). Analysis for repeated events and on-treatment analysis with any renin-angiotensin-aldosterone-system-inhibitor did not alter these results. CONCLUSIONS: Valsartan treatment in systemic RV patients did not result in improved survival at longer-term follow-up, but was associated with decreased risk of events in symptomatic patients.

[Mitral valve insufficiency; undertreated or not?] / Mitralisklepinsufficiëntie.

Dziadzko et al. describe the poor prognosis and low performance of surgery (15%) in a large cohort of patients with isolated moderate to severe mitral regurgitation (MR). They report a prevalence of moderate-severe MR 'in the community'. This is misleading as these patients were referred for echocardiography. Second, the authors stated there was 'important undertreatment' of MR as only 15% underwent surgery. Moderate MR was present in 70% and according to the 2006 guidelines, surgery for moderate MR is a class III recommendation. Finally, the authors report that few patients received 'the only treatment available (surgery)' and call for action. However, from the beginning of this century, treatment options have been extended by means of cardiac resynchronization therapy and the Mitraclip procedure. As nowadays these options account for up to 10% of non-pharmacological interventions of the mitral valve, not considering these modalities in the paper limits its value.

Contemporary survival of adults with congenital heart disease.

BACKGROUND: Survival data that are applicable to the current population of adults with congenital heart disease (CHD) are not available. OBJECTIVES: Using an alternative survival analysis with age as the primary time scale, we assessed the contemporary survival of adult patients with CHD. METHODS: Survival was assessed using prospective data of the national registry of adult patients with CHD of the Netherlands. Survival was stratified by severity and lesion, and compared with a standardised general population. RESULTS: Mean age at inclusion was 37 years, and 49% of the study population was male. During a cumulative prospective follow-up of 90, 270 patient-years in 14, 327 patients, 535 deaths occurred. Median survival was 53.4 (95% CI 49.9 to 60.7), 75.4 (95% CI 72.9 to 79.1) and 84.1 (95% CI 81.9 to 87.0) years for patients with severe, moderate and mild lesions, respectively. Survival of most patients with mild lesions did not differ from the general population, while, as expected, survival of patients with severe and moderate lesions was substantially lower (<0.001). CONCLUSIONS: The present study gives insight in the contemporary survival of adults with CHD. This may aid patient counselling, timing of interventions and future research.

Secundum atrial septal defect is associated with reduced survival in adult men.

AIMS: The identification of sex differences in the prognosis of adults with a secundum atrial septal defect (ASD2) could help tailor their clinical management, as it has in other cardiovascular diseases. We investigated whether disparity between the sexes exists in long-term outcome of adult ASD2 patients. METHODS AND RESULTS: Patients with ASD2 classified as the primary defect were selected from the Dutch national registry of adult congenital heart disease. Survival stratified by sex was compared with a sex-matched general population. In a total of 2207 adult patients (mean age at inclusion 44.8 years, 33.0% male), 102 deaths occurred during a cumulative follow-up of 13 584 patient-years. Median survival was 79.7 years for men and 85.6 years for women with ASD2. Compared with the age- and sex-matched general population, survival was lower for male, but equal for female patients (P = 0.015 and 0.766, respectively). Logistic regression analyses showed that men had a higher risk of conduction disturbances (OR = 1.63; 95% CI, 1.22-2.17) supraventricular dysrhythmias (OR = 1.41; 1.12-1.77), cerebrovascular thromboembolic events (OR = 1.53; 1.10-2.12), and heart failure (OR = 1.91; 1.06-3.43). CONCLUSION: In contrast to women, adult men with an ASD2 have worse survival than a sex-matched general population. Male patients also have a greater risk of morbidity during adult life. Sex disparity in survival and morbidity suggests the need for a sex-specific clinical approach towards these patients.

Long-term benefits of exercise training in patients with a systemic right ventricle.

OBJECTIVES: The aim of the present study is to determine the long-term effects of a ten-week exercise training program in adult patients with a systemic right ventricle. METHODS: All patients who participated in a 2009 randomized controlled trial were approached. At approximately three years of follow-up from initial baseline, patients underwent cardiopulmonary exercise testing, filled out two quality of life questionnaires, and NT proBNP levels were measured. All examinations were performed according to the protocols of the 2009 trial. In addition, patients were asked about their current sports habits. RESULTS: Of the 54 patients who were randomized in the 2009-trial 40 participated in the current re-evaluation (male 50%, ccTGA 35%, age 36 ± 10 years, intervention group n=22, control group n=18). After three years, no persistent effect of exercise training on V'O2peak training remained (-2% of predicted, 95% CI -3% to 5%; p=.56). However, patients who already participated in regular sports or exercise at baseline (n=23/40 (58%)) showed higher V'O2peak of 13% of predicted (95% CI 4% to 23%; p>.01) and a decrease of 62% in plasma NT-proBNP (95% CI -115% to -10%; p>.03) during follow-up, when compared to patients who did not. Moreover, sports were associated with a lower incidence of clinical events (p=.032). CONCLUSION: Short-term beneficial effects of exercise training did not persist over a three-year follow-up period. However, sports participation at baseline was associated with better exercise capacity, lower neurohormone levels, and increased event-free survival.

Evaluating the systemic right ventricle by cardiovascular magnetic resonance: short axis or axial slices?

OBJECTIVE: To evaluate differences in functional parameters and reproducibility between short axis and axial slice orientation in the quantitative evaluation of the systemic right ventricle by cardiovascular magnetic resonance. DESIGN: Cross-sectional evaluation comparing two methods (Bland-Altman). SETTING: Tertiary care outpatients. INTERVENTIONS: Quantitative cardiovascular magnetic resonance evaluation using short axis or axial slice orientation. MAIN OUTCOME MEASURES: Intraobserver variance, interobserver variance and systematic differences in systemic right ventricular volumes, ejection fraction, and mass between both methods. PATIENTS: Twenty-two patients (mean age 33 ± 7 years) with systemic right ventricle (three with congenitally corrected transposition of the great arteries and 19 with atrially switched transposition of the great arteries). RESULTS: Compared with short axis slices, analysis of axial slices resulted in higher end systolic volume (6.6%, P < .01), while mass (-10.8%, P < .01) and ejection fraction (-8.9%, P < .01) turned out lower. Intraobserver and interobserver reproducibility were similar for both methods when measuring end-diastolic and end-systolic volumes. However, ejection fraction and stroke volume were measured more consistently in axial orientation, while ventricular mass was measured more consistently in short axis orientation. CONCLUSION: There are significant differences in volume, mass, and function between measurements in axial and short axis orientation. Ejection fraction and stroke volume, which have a high clinical relevance, were measured more consistently in axial slice orientation. Consequently, we recommend using axial slice orientation in patients with a systemic right ventricle.

Persistent neo-aortic growth during adulthood in patients after an arterial switch operation.

OBJECTIVE: After the arterial switch operation (ASO), disproportional neo-aortic growth during childhood has been reported. Even though it has been suggested neo-aortic dilation will stabilise in adulthood, data are lacking. The aim of this study was to assess the change in neo-aortic dimensions, prevalence of neo-aortic dilation >40 mm and long-term outcome in adults who underwent ASO in childhood. METHODS: All 116 ASO patients operated in a tertiary referral centre and born before 1995 were included. Of these, 83 (72%) survived to adulthood (>17 years) and six were lost to follow-up. Neo-aortic measurements performed in adulthood were collected from available echocardiographic, cardiovascular magnetic resonance and CT images. The time trend was analysed using a mixed model, adjusted for imaging modality. RESULTS: Clinical data with at least one measurement of the neo-aortic diameter were available in 77 (93%) adult patients and serial measurements in 65 (78%). At baseline (median age 18.1 years), mean neo-aortic diameter was 36±5 mm. Mean neo-aortic growth was 0.31 mm/year (p<0.001 compared with normal value 0.08 mm/year) and was linear over time. Freedom from neo-aortic dilation beyond a diameter of 40 mm was 23% at 28 years of age. During a mean clinical follow-up in adulthood of 7.2 years (IQR 4.0 to 10.1), 3 (4%) patients underwent neo-aortic replacement. No other neo-aortic complications occurred. CONCLUSIONS: In early adulthood, neo-aortic growth was on average linear and did not stabilise over time.

Right ventricular end-diastolic volume combined with peak systolic blood pressure during exercise identifies patients at risk for complications in adults with a systemic right ventricle.

OBJECTIVES: The aim of this study was to identify which patients with a systemic right ventricle are at risk for clinical events. BACKGROUND: In patients with congenitally or atrially corrected transposition of the great arteries, worsening of the systemic right ventricle is accompanied by clinical events such as clinical heart failure or the occurrence of arrhythmia. METHODS: At baseline, all subjects underwent electrocardiography, echocardiography, cardiopulmonary exercise testing, and cardiovascular magnetic resonance imaging. Clinical events comprised death, vascular events, tricuspid regurgitation requiring surgery, worsening heart failure, and (supra)ventricular arrhythmia. A Cox proportional hazards analysis was used to assess the most valuable determinants of clinical events. RESULTS: A total of 88 patients with a mean age of 33 years were included in the study. Sixty-five percent were men, and 28% had congenitally corrected transposition of the great arteries. During a follow-up period of 4.3 years, 31 patients (35%) experienced 46 clinical events for an annual risk of 12%. Right ventricular end-diastolic volume index measured by means of cardiovascular magnetic resonance imaging or multirow detector computed tomography (hazard ratio: 1.20; p < 0.01) and peak exercise systolic blood pressure (hazard ratio: 0.86; p = 0.02) were the strongest determinants of clinical events. Patients with a right ventricular end-diastolic volume index above 150 ml/m(2) and peak exercise systolic blood pressure below 180 mm Hg were most likely to experience clinical events with an annual event rate of 19% versus 0.9% in patients without these risk factors. CONCLUSIONS: Patients with a right ventricular end-diastolic volume index above 150 ml/m(2) and peak exercise systolic blood pressure below 180 mm Hg had a 20-fold higher annual event rate than patients without these risk factors. Regular cardiovascular magnetic resonance imaging and exercise testing are important in the risk assessment of these patients.

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, Vo(2)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.

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.

Exercise training improves exercise capacity in adult patients with a systemic right ventricle: a randomized clinical trial.

OBJECTIVE: To assess whether exercise training in adult patients with a systemic right ventricle (RV) improves exercise capacity and quality of life and lowers serum N-terminal prohormone brain natriuretic peptide (NT-proBNP) levels. DESIGN: Multi-centre parallel randomized controlled trial. PARTICIPANTS: Patients with a systemic RV due to congenitally or surgically corrected transposition of the great arteries. METHODS: Fifty-four adult patients with a systemic RV, were randomized using unmarked opaque envelopes to an intervention group (n = 28) with three training sessions per week for 10 consecutive weeks, and a control group (n = 26). Randomization was stratified by participating centre. At baseline, and follow-up, we determined maximal exercise capacity (V'O(2peak)), serum NT-proBNP levels, and quality of life by means of the SF-36, and the TAAQOL Congenital Heart Disease questionnaires. The final analysis was performed by linear regression, taking into account the stratified randomization. RESULTS: Forty-six patients were analysed (male 50%, age 32 ± 11 years, intervention group n = 24, control group n = 22). Analysis at 10 weeks showed a significant difference in V'O(2peak) (3.4 mL/kg/min, 95% CI: 0.2 to 6.7; P = 0.04) and resting systolic blood pressure (-7.6 mmHg, 95% CI: -14.0 to -1.3; P = 0.03) in favour of the exercise group. No significant changes were found in serum NT-proBNP levels or quality of life in the intervention group or in the control group nor between groups. None of the patients in the intervention group had to discontinue the training programme due to adverse events. CONCLUSION: In adult patients with a systemic RV exercise training improve exercise capacity. We recommend to revise restrictive guidelines, and to encourage patients to become physically active. ( TRIAL REGISTRATION: The study was registered at http://trialregister.nl. Identifier: NTR1909.).

Treatment of congenital heart disease: risk-reducing measures in young adults.

Adults with congenital heart disease form a new and relatively young population, since surgical treatment of heart defects became available three to four decades ago. Owing to improved survival this population is steadily growing in number and age. Little is known regarding long-term survival; however, late complications occur frequently. During adulthood, almost half of the patients have one or more complication, such as endocarditis, stroke, systemic or pulmonary hypertension, aortic aneurysm or dissection and arrhythmias. Heart failure and sudden cardiac death are the main causes of death. Treatment of adults with congenital heart disease is aimed at the reduction of symptoms, but also at minimizing the risk and severity of late complications. In this article the most recent advances in the treatment of congenital heart disease will be discussed. The main focus of the article will be on pharmacological, interventional and surgical interventions that reduce the risk of heart failure, arrhythmias, vascular complications, pulmonary hypertension and endocarditis.

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.

Rationale and design of a trial on the effect of angiotensin II receptor blockers on the function of the systemic right ventricle.

BACKGROUND: Angiotensin II receptor blockers have been proven to be beneficial in left ventricular failure. In patients with a morphologic right ventricle supporting the systemic circulation, its efficacy has not yet been established. METHODS: We designed a multicenter, prospective, randomized, double-blind, placebo-controlled trial studying the effect of valsartan in patients with a systemic right ventricle due to a congenitally or surgically corrected transposition of the great arteries. The primary end point is the change in right ventricular ejection fraction as measured by cardiovascular magnetic resonance or multidetector row cardiac computed tomography in case of pacemaker patients. CONCLUSION: This large prospective, double-blind, randomized, placebo-controlled trial will establish the role of angiotensin II receptor blockers (valsartan) in the treatment of patients with a systemic right ventricle.