Pieter De Meester

Sildenafil improves exercise hemodynamics in Fontan patients.

Background—Patients with Fontan circulation have reduced exercise capacity. The absence of a presystemic pump may limit flow through the pulmonary circulation, restricting ventricular filling and cardiac output. We evaluated exercise hemodynamics and the effect of sildenafil on exercise hemodynamics in Fontan patients. Methods and Results—Ten Fontan patients (6 men, 20±4 years) underwent cardiac magnetic resonance imaging at rest and during supine bicycle exercise before and after sildenafil. Systemic ventricular volumes were obtained at rest and during low- (34±15 W), moderate- (69±29 W), and high-intensity (97±36 W) exercise using an ungated, free-breathing cardiac magnetic resonance sequence and analyzed correcting for cardiac phase and respiratory translation. Radial and pulmonary artery pressures and cGMP were measured. Before sildenafil, cardiac index increased throughout exercise (4.0±0.9, 5.9±1.1, 7.0±1.6, 7.4±1.7 L/(min·m2); P<0.0001) with 106±49% increase in heart rate. Stroke volume index (P=0.015) and end-diastolic volume index (P=0.001) decreased during exercise. End-systolic volume index remained unchanged (P=0.8). Total pulmonary resistance index (P=0.005) increased, whereas systemic vascular resistance index decreased during exercise (P<0.0001). Sildenafil increased cardiac index (P<0.0001) and stroke volume index (P=0.003), especially at high-intensity exercise (interaction P=0.004 and P=0.003, respectively). Systemic vascular resistance index was reduced (P<0.0001–interaction P=0.1), whereas total pulmonary resistance index was reduced at rest and reduced further during exercise (P=0.008–interaction P=0.029). cGMP remained unchanged before sildenafil (P=0.9), whereas it increased significantly after sildenafil (P=0.019). Conclusions—In Fontan patients, sildenafil improved cardiac index during exercise with a decrease in total pulmonary resistance index and an increase in stroke volume index. This implies that pulmonary vasculature represents a physiological limitation, which can be attenuated by sildenafil, the clinical significance of which warrants further study.

A different view on predictors of pulmonary hypertension in secundum atrial septal defect

BACKGROUND/OBJECTIVES Pulmonary arterial hypertension is an important complication in hemodynamically relevant atrial septal defects (ASD) and negatively affects outcome. This retrospective study aimed at (1) estimating the prevalence of pulmonary hypertension (PH) in patients with secundum ASD and (2) identifying predictors of PH development or persistence after ASD closure. METHODS Consecutive patients with an isolated secundum ASD from the Belgian Registry on Adult Congenital Heart Disease were studied. Demographic, clinical, echocardiographic and invasive hemodynamic measurements were analyzed. PH was defined upon the echocardiographic PH probability (tricuspid regurgitation velocity≥2.9 m/s). RESULTS PH prevalence in the entire ASD population (295 patients, 68.8% females, mean age 46±21 years) was 15.9% compared to 13.3% in patients after ASD closure. PH after ASD closure was significantly related to mortality (p=0.001), atrial arrhythmia (p<0.001) and right heart failure (p=0.019). Age at repair was the most important predictor for PH (HR 1.11). In the highest tertile of age at repair (>55 years), PH prevalence was the highest (34%) and mean pulmonary artery pressure (mPAP) at catheterization before was related to PH after closure (HR 1.09). Twenty patients in the PH group had mPAP<25 mmHg before closure. CONCLUSIONS PH in closed secundum ASD patients is not uncommon. Its prevalence was the highest when the defect was repaired above 55 years of age. Clinical outcome was worse. PH may even develop despite normal mPAP before closure. The present findings raise the question whether the cutoff value for mPAP before closure should be age-adjusted.

Right Ventricular Function in Patients With Eisenmenger Syndrome

To evaluate (1) whether right ventricular (RV) dysfunction, evaluated using tricuspid annular plane systolic excursion (TAPSE) is associated with a worse outcome in patients with the Eisenmenger syndrome, (2) which variables are related to RV dysfunction, and (3) whether differences exist among simple pretricuspid, simple post-tricuspid, and combined shunt lesions. Patients with Eisenmenger syndrome, aged >18 years, who underwent echocardiography, were selected from the Belgian Eisenmenger registry and prospectively followed up using a Web-based registry. Cox regression analysis was performed to evaluate the relation to outcomes, defined as all-cause mortality, transplantation, and hospitalization for cardiopulmonary causes. Comparative and bivariate analysis was performed, where applicable. A total of 58 patients (mean age 35.1 ± 13.2 years, 32.8% men) were included. During a mean follow-up of 3.2 years, 22 patients (37.9%) reached the predefined end point. Only TAPSE (hazard ratio 0.820, 95% confidence interval 0.708 to 0.950; p = 0.008) was related to the adverse outcomes on multivariate analysis. Patients with pretricuspid shunt lesions were older (p <0.0001) had greater left (p <0.0001) and right atrial (p <0.0001) dimensions, greater RV dimensions (p = 0.002), and more tricuspid regurgitation (p = 0.012) compared to patients with post-tricuspid lesions. Lower TAPSE was related to the presence of pulmonary artery thrombosis (R = -0.378; p = 0.006). In conclusion, in patients with Eisenmenger syndrome, RV dysfunction, evaluated using TAPSE, is related to worse outcomes. Patients with Eisenmenger syndrome with pretricuspid shunt lesions were older and had greater left atrial, right atrial, and RV dimensions compared to patients with post-tricuspid lesions, indicating a difference in the RV response. Lower TAPSE was associated with the presence of pulmonary artery thrombosis.

Worsening in oxygen saturation and exercise capacity predict adverse outcome in patients with Eisenmenger syndrome

OBJECTIVES To evaluate (1) changes in clinical, biochemical and echocardiographic parameters, (2) whether deterioration in exercise capacity and resting oxygen saturation (SatO2-rest) are related with adverse outcome and (3) its additional value in predicting outcome in Eisenmenger patients. METHODS Seventy-seven (36 ± 14 years, 30% male) patients were included and prospectively followed. Changes between baseline and final visit were evaluated. Clinical deterioration was defined as a deterioration in exercise capacity or SatO2-rest. Univariate and multivariate analyses were performed to evaluate predictors of outcome defined as the need for hospitalization due to right heart failure, transplantation, or all-cause mortality. Finally, the additional prognostic value of deterioration in exercise capacity and SatO2-rest was evaluated. RESULTS During a mean follow-up period of 4.0 ± 2.1 years, 27 (35%) events occurred. Patients in the event-group presented with an deterioration in NYHA class (P<0.0001), 6 minute walk distance (P=0.006) and SatO2-rest (P<0.0001). After adjustment for baseline variables, multivariate Cox regression analysis indicated that clinical deterioration was independently associated with adverse outcome. CONCLUSIONS Clinical deterioration, defined as a deterioration in exercise capacity or SatO2-rest was associated with adverse outcome in Eisenmenger patients. Moreover, these parameters provided additional information on which patients would develop an event and may benefit from initiation or escalation of disease targeting therapy.

Right ventricular load and function during exercise in patients with open and closed atrial septal defect type secundum

Purpose: This study aimed at evaluating (1) right ventricular (RV) mean power during exercise, (2) the contribution of flow and pressure to RV mean power, and (3) the impact of pulmonary artery pressure on RV function during exercise. Methods: Fifty patients with atrial septal defect (ASD) type secundum (20 open, 30 closed) were enrolled. All underwent standard echocardiography, a bicycle stress echocardiography, and symptom-limited cardiopulmonary exercise testing. RV mean power was calculated as the product of RV cardiac output and mean pulmonary artery pressure (mPAP). RV function was assessed using RV fractional area change (FAC) at rest and at peak exercise. Results: RV mean power was linearly related with oxygen uptake (VO2) in patients with open (R2 = 0.88; p < 0.0001) and closed ASD (R2 = 0.90; p < 0.0001). The increase in RV mean power was steeper in open than in closed ASD patients (p < 0.0001). The change in RV cardiac output (7.1 ± 3.4 vs. 5.7 ± 2.4 l/min; p = 0.132) was not statistically different, but the change in mPAP (21.7 ± 9.6 vs. 12.8 ± 4.6 mmHg; p < 0.0001) and RV mean power (0.97 ± 0.56 vs. 0.53 ± 0.22 W; p = 0.009) were higher in patients with an open ASD. The change in RV FAC from rest to peak exercise was related to peak mPAP in open (R = −0.589; p = 0.010) and closed (R = −0.450; p = 0.021) ASD patients. Conclusion: RV mean power during exercise is higher in patients with an open than in patients with a closed ASD. The workload of the RV in patients with an open ASD is higher at rest due to a left-to-right shunt, at peak exercise due to an additional increase in mPAP. A higher increase in afterload may affect RV function during exercise.

Prevention of stroke by percutaneous left atrial appendage closure: Short term follow-up

Preliminary studies suggest that left atrial appendage (LAA) closure might be beneficial in the prevention of stroke in patients with atrial fibrillation (AF). We evaluated the preliminary clinical efficacy of percutaneous LAA closure using the PLAATO-device (ev3 Endovascular, Inc., North Plymouth, MN) and found that none of the patients suffered from thrombo-embolic events within a time period of 2 years after successful LAA closure. Therefore, we believe that percutaneous closure of the LAA might be a valuable technique for AF patients with contra-indications for or failure of oral anticoagulation to prevent thrombo-embolic events.

Additional tricuspid annuloplasty in mitral valve surgery results in better clinical outcome

Objective The clinical benefit of tricuspid annuloplasty (TA) in patients undergoing mitral valve surgery (MVS) is still debated. We evaluated the immediate surgical success, postoperative outcome and the medium-term effect of TA in MVS. Methods Patients were included between September 2003 and December 2009 and followed until September 2013 to achieve a median follow-up time of 5 years (IQR 3.7–6.9). The end point of mortality due to cardiac causes and combined end point of cardiac mortality or hospitalisation for heart failure were evaluated. Propensity score adjusted Cox regression was used to evaluate the clinical benefit of TA at the time of MVS. Results Of 150 patients (84 female; 67±12 years), 82 presented with tricuspid regurgitation (TR) <2/4 and underwent isolated MVS. Of 68 patients presenting with TR≥2/4, 31 underwent isolated MVS whereas 37 underwent additional TA. In patients with preoperative TR≥2/4, TR was significantly reduced until 5 years postoperatively (mean reduction 0.81±1.31; p=0.04) when additional TA was done. The combined end point occurred in 29% vs 6% at 1 year and in 57% vs 39% at 5 years follow-up for patients with isolated MVS and patients undergoing concomitant TA, respectively. Patients with preoperative TR≥2/4 had worse unadjusted survival than those with TR<2/4 (logrank p=0.009). In the patients with TR≥2/4, propensity score-adjusted risk for the combined end point was higher in those with isolated MVS versus MVS with additional TA (Cox HR 2.855 (1.082–7.532), p=0.035). Conclusions Additional TA is an effective surgical measure to reduce functional TR severity. This approach results in a decreased risk of cardiac mortality and hospitalisation in patients with preoperative TR≥2/4.

Left atrial appendage occlusion: Single center experience with PLAATO LAA Occlusion System® and AMPLATZER™ Cardiac Plug

OBJECTIVES To evaluate patient selection, safety, feasibility, and midterm results of percutaneous left atrial appendage (LAA) occlusion. BACKGROUND Oral anticoagulants (OAC) are the gold standard for stroke prevention in most patients with atrial fibrillation (AF). As the LAA is the main source of AF-related thrombi, LAA occlusion might reduce the thromboembolic (TE) risk. Recently, LAA closure was implemented in the European Society of Cardiology guidelines for the management of AF. METHODS This retrospective single center study examined all LAA percutaneous closures (September 2003-September 2011). RESULTS Twenty-five patients were included in the study; median age at closure was 73 years (minimum maximum range 49-85 years), 68% men. Median CHA2DS2-VASc score and HAS-BLED score were 5 (IQR 4-6) and 4 (IQR 4-5), respectively. Most frequent reason for LAA closure was intracranial hemorrhage during OAC treatment (52%). Successful device implantation was achieved in 96%. During a follow-up of 60.6 patient years, the TE stroke event rate was 4.95 per 100 patient years, versus an expected rate of 8.78 and 2.90 without and with OAC, respectively. No peripheral embolism occurred. Major procedure-related adverse events occurred in two patients. CONCLUSIONS Percutaneous closure of the LAA is feasible and safe. Intracranial hemorrhage was the most important indication for LAA closure. A low number of TE stroke events occurred during follow-up. LAA closure might be a good alternative in patients with a firm contraindication for OAC.

Pulmonary outflow obstruction protects against heart failure in adults with congenitally corrected transposition of the great arteries

BACKGROUND Pulmonary outflow tract obstruction (POTO) reduces systemic atrioventricular valve (SAVV) regurgitation severity in congenitally corrected transposition of the great arteries (ccTGA). Therefore, pulmonary artery banding is proposed as a palliative intervention. We aimed to investigate the effect of native or surgically induced POTO on event-free survival, defined as the composite of all-cause mortality, heart transplantation, or congestive heart failure (CHF). METHODS AND RESULTS Patients with ccTGA (n=62; median age 27.5 (IQR 18.4-39.4) years; 39% with POTO) were selected from the Adult Congenital Heart Disease database of a tertiary hospital. At first visit, SAVV regurgitation ≥ 3/4, systemic RV dysfunction ≥ moderate, and CHF were present in 26%, 26%, and 15% of patients, respectively. Over a mean follow-up time of 10.1 ± 6.1 years, all-cause mortality, rate of heart transplantation, and CHF were 18%, 8% and 40%, respectively. SAVV regurgitation (HR: 1.99; 95% CI: 1.01-3.92; P=0.048) and systemic RV dysfunction severity (HR: 1.89; 95% CI: 1.05-3.37; P=0.033) were associated with the composite endpoint, independently of age at baseline, POTO, Ebstein-like malformation, and systemic RV dilatation. Patients with POTO had lower risk for developing SAVV regurgitation ≥ 3/4 (HR: 0.18; 95% CI: 0.05-0.58; P=0.004) and moderate systemic RV dysfunction (HR: 0.34; 95% CI: 0.15-0.78; P=0.011). When POTO was present, the mean progression-free interval for the composite endpoint increased from 11.2 to 18.1 years (P=0.035). CONCLUSIONS POTO is associated with an improved event-free survival in adults with ccTGA.

Clinical significance of dynamic pulmonary vascular resistance in two populations at risk of pulmonary arterial hypertension

AIMS Patients at risk of pulmonary arterial hypertension (PAH) may present with abnormal dynamic pulmonary vascular resistance (PVR) during exercise. However, its clinical significance remains unclear. The present study aimed at analysing the meaning of dynamic PVR in two populations at risk of PAH: secundum atrial septal defect (ASD) and systemic sclerosis (SSc). METHODS AND RESULTS Adult patients with corrected ASD were consecutively selected from the database of Pediatric and Congenital Heart Disease of the University Hospitals Leuven. Patients with SSc were consecutively selected from the rheumatology database of the University Hospital Liège. At inclusion, all underwent a rest and bicycle stress echocardiography to obtain baseline right heart characteristics and dynamic PVR. Routine follow-up echocardiography was performed. Twenty-eight patients with corrected ASD (mean age 41 ± 17 years, 79% female) were followed for a median time of 3.7 [inter-quartile range (IQR) 2.9-4.1] years. No patient developed PAH. Dynamic PVR was significantly associated with right atrial dilatation at latest follow-up (Spearmans ρ 0.51, P = 0.013). Forty-five SSc patients (mean age 54 ± 13 years, 76% female) were followed for a median time of 2.4 (IQR 0.8-2.9) years. Thirteen patients (30%) developed PAH. Dynamic PVR was the only independent predictor of PAH (hazards ratio 1.22, 95% confidence interval 1.01-1.47). No significant right heart morphometric changes occurred. CONCLUSION Dynamic PVR predicted PAH development in patients with SSc, whereas dynamic PVR was associated with right heart morphometric changes after ASD closure. The predictive role of dynamic PVR might depend on the underlying disease type. Larger studies are needed to confirm this hypothesis.