Johannes Nordmeyer

Percutaneous pulmonary valve implantation impact of evolving technology and learning curve on clinical outcome

Background— Percutaneous pulmonary valve implantation was introduced in the year 2000 as a nonsurgical treatment for patients with right ventricular outflow tract dysfunction. Methods and Results— Between September 2000 and February 2007, 155 patients with stenosis and/or regurgitation underwent percutaneous pulmonary valve implantation. This led to significant reduction in right ventricular systolic pressure (from 63±18 to 45±13 mm Hg, P<0.001) and right ventricular outflow tract gradient (from 37±20 to 17±10 mm Hg, P<0.001). Follow-up ranged from 0 to 83.7 months (median 28.4 months). Freedom from reoperation was 93% (±2%), 86% (±3%), 84% (±4%), and 70% (±13%) at 10, 30, 50, and 70 months, respectively. Freedom from transcatheter reintervention was 95% (±2%), 87% (±3%), 73% (±6%), and 73% (±6%) at 10, 30, 50, and 70 months, respectively. Survival at 83 months was 96.9%. On time-dependent analysis, the first series of 50 patients (log-rank test P<0.001) and patients with a residual gradient >25 mm Hg (log-rank test P=0.01) were associated with a higher risk of reoperations. Conclusions— Percutaneous pulmonary valve implantation resulted in the ability to avoid surgical right ventricular outflow tract revision in the majority of cases. This procedure might reduce the number of operations needed over the total lifetime of patients with right ventricle–to–pulmonary artery conduits.

Risk Stratification, Systematic Classification, and Anticipatory Management Strategies for Stent Fracture After Percutaneous Pulmonary Valve Implantation

Background— We analyzed the incidence, risk factors and treatment options for stent fracture after percutaneous pulmonary valve (PPV) implantation (PPVI). Methods and Results— After PPVI, 123 patients had chest x-ray in anteroposterior and lateral projection, echocardiography, and clinical evaluation during structured follow-up. Of these 123 patients, 26 (21.1%) developed stent fracture 0 to 843 days after PPVI (stent fracture–free survival at 1 year, 85.1%; at 2 years, 74.5%; and at 3 years, 69.2%). Stent fracture was classified as type I: no loss of stent integrity (n=17); type II: loss of integrity with restenosis on echocardiography (n=8); and type III: separation of fragments or embolization (n=1). In a multivariate Cox regression, we analyzed various factors, of which 3 were associated with a higher risk of stent fracture: implantation into “native” right ventricular outflow tract (P=0.04), no calcification along the right ventricular outflow tract (judged with fluoroscopy, P=0.02), recoil of PPV (qualitatively, PPV diameter in frontal or lateral plane with fully inflated balloon > diameter after balloon deflation, P=0.03). Substernal PPV location, high-pressure post-PPVI dilatation of PPV, pre-PPVI right ventricular outflow tract gradients, and other indicators of PPV compression or asymmetry did not pose increased risk. Patients with type I fracture remain under follow-up. Patients with type II fracture had 2nd PPVI or are awaiting such procedure, and 1 patient with type III fracture required surgical explantation. Conclusion— Stent fracture after PPVI can be managed effectively by risk stratification, systematic classification, and anticipatory management strategies. Serial x-ray and echocardiography are recommended for surveillance.

Upregulation of Myocardial Estrogen Receptors in Human Aortic Stenosis

Background—Estrogen receptor (ER)–mediated effects have been associated with the modulation of myocardial hypertrophy in animal models and in humans, but ER expression in the human heart and its relation to hypertrophy-mediated gene expression have not yet been analyzed. We therefore investigated sex- and disease-dependent alterations of myocardial ER expression in human aortic stenosis together with the expression of hypertrophy-related genes. Methods and Results—ER-&agr; and -&bgr;, calcineurin A-&bgr;, and brain natriuretic peptide (BNP) mRNA were quantified by real-time polymerase chain reaction in left ventricular biopsies from patients with aortic valve stenosis (n=14) and control hearts with normal systolic function (n=17). ER protein was quantified by immunoblotting and visualized by immunofluorescence confocal microscopy. ER-&agr; mRNA and protein were increased 2.6-fold (P=0.003) and 1.7-fold (P=0.026), respectively, in patients with aortic valve stenosis. Left ventricular ER-&bgr; mRNA was increased 2.6-fold in patients with aortic valve stenosis (P<0.0001). ER-&agr; and -&bgr; were found in the cytoplasm and nuclei of human hearts. A strong inverse correlation exists between ER-&bgr; and calcineurin A-&bgr; mRNA in patients with aortic valve stenosis (r=−0.83, P=0.002) but not between ER-&agr; or -&bgr; and BNP mRNA. Conclusions—ER-&agr; and -&bgr; in the human heart are upregulated by myocardial pressure load.

Pre-stenting with a bare metal stent before percutaneous pulmonary valve implantation: acute and 1-year outcomes

Objectives To determine the feasibility and safety of pre-stenting with a bare metal stent (BMS) before percutaneous pulmonary valve implantation (PPVI), and to analyse whether this approach improves haemodynamic outcomes and impacts on the incidence of PPVI stent fractures. Design Retrospective analysis of prospectively collected data. Setting Tertiary paediatric and adult congenital heart cardiac centre. Patients and interventions 108 consecutive patients with congenital heart disease underwent PPVI between September 2005 and June 2008 (54 with PPVI alone, 54 with BMS pre-stenting before PPVI). Results There were no significant differences in procedural complication rates. Acutely, there was no difference in haemodynamic outcomes. Serial echocardiography revealed that in the subgroups of ‘moderate’ (26–40 mm Hg) and ‘severe’ (>40 mm Hg) right ventricular outflow tract (RVOT) obstruction, patients with pre-stenting showed a tendency towards lower peak RVOT velocities compared to patients after PPVI alone (p=0.01 and p=0.045, respectively). The incidence of PPVI stent fractures was not statistically different between treatment groups at 1 year (PPVI 31% vs BMS+PPVI 18%; p=0.16). However, pre-stenting with BMS was associated with a lower risk of developing PPVI stent fractures (HR 0.35, 95% CI 0.14 to 0.87, p=0.024). The probability of freedom from serious adverse follow-up events (death, device explantation, repeat PPVI) was not statistically different at 1 year (PPVI 92% vs BMS+PPVI 94%; p=0.44). Conclusions Pre-stenting with BMS before PPVI is a feasible and safe modification of the established implantation protocol. Pre-stenting is associated with a reduced risk of developing PPVI stent fractures.

Early Versus Late Functional Outcome After Successful Percutaneous Pulmonary Valve Implantation Are the Acute Effects of Altered Right Ventricular Loading All We Can Expect

OBJECTIVES The purpose of this study was to assess the potential of late positive functional remodeling after percutaneous pulmonary valve implantation (PPVI) in right ventricular outflow tract dysfunction. BACKGROUND PPVI has been shown to impact acutely on biventricular function and exercise performance, but the potential for further late functional remodeling remains unknown. METHODS Sixty-five patients with sustained hemodynamic effects of PPVI at 1 year were included. Patients were divided into 2 subgroups based on pre-procedural predominant pulmonary stenosis (PS) (n = 35) or predominant pulmonary regurgitation (PR) (n = 30). Data from magnetic resonance imaging and cardiopulmonary exercise testing were compared at 3 time points: before PPVI, within 1 month (early) and at 12 months (late) after PPVI. RESULTS There was a significant decrease in right ventricle end-diastolic volume early after PPVI in both subgroups of patients. Right ventricle ejection fraction improved early only in the PS group (51 ± 11% vs. 58 ± 11% and 51 ± 12% vs. 50 ± 11%, p < 0.001 for PS, p = 0.13 for PR). Late after intervention, there were no further changes in magnetic resonance parameters in either group (right ventricle ejection fraction, 58 ± 11% in the PS group and 52 ± 11% in the PR group, p = 1.00 and p = 0.13, respectively). In the PS group at cardiopulmonary exercise testing, there was a significant improvement in peak oxygen uptake early (24 ± 8 ml/kg/min vs. 27 ± 9 ml/kg/min, p = 0.008), with no further significant change late (27 ± 9 ml/kg/min, p = 1.00). In the PR group, no significant changes in peak oxygen uptake from early to late could be demonstrated (25 ± 8 ml/kg/min vs. 25 ± 8 ml/kg/min vs. 26 ± 9 ml/kg/min, p = 0.48). CONCLUSIONS In patients with a sustained hemodynamic result 1 year after PPVI, a prolonged phase of maintained cardiac function is observed. However, there is no evidence for further positive functional remodeling beyond the acute effects of PPVI.

Improvement in left ventricular filling properties after relief of right ventricle to pulmonary artery conduit obstruction: contribution of septal motion and interventricular mechanical delay.

AIMS To investigate the impact of relief of right ventricle (RV) to pulmonary artery (PA) conduit obstruction on septal motion and ventricular interaction and its functional implications for left ventricular (LV) filling properties. METHODS AND RESULTS In 20 consecutive patients with congenital heart disease and RV to PA conduit obstruction, the following were prospectively assessed before and after percutaneous pulmonary valve implantation (PPVI): the septal curvature and LV volumes throughout the cardiac cycle by magnetic resonance imaging; RV to LV mechanical delay by 2D-echocardiographic strain imaging; and objective exercise capacity. Percutaneous pulmonary valve implantation led to a reduction in RV to LV mechanical delay (127.9 +/- 50.9 vs. 37.7 +/- 35.6 ms; P < 0.001) and less LV septal bowing in early LV diastole (septal curvature: -0.11 +/- 0.11 vs. 0.07 +/- 0.13 cm(-1); P < 0.001). Early LV diastolic filling (first one-third of diastole) increased significantly (17.5 +/- 9.4 to 30.4 +/- 9.4 mL/m(2); P < 0.001). The increase in early LV diastolic filling correlated with the reduction in RV to LV mechanical delay (r = -0.68; P = 0.001) and change in septal curvature (r = 0.71; P < 0.001). In addition, the improvement in peak oxygen uptake (56.0 +/- 16.0 vs. 64.1 +/- 13.7% of predicted; P < 0.001) was associated with the increase in early LV diastolic filling (r = 0.69; P = 0.001). CONCLUSION Relief of RV to PA conduit obstruction significantly improves early LV filling properties. This is attributed to more favourable septal motion and reduction in interventricular mechanical delay.

Patient-specific simulations of transcatheter aortic valve stent implantation

Transcatheter aortic valve implantation (TAVI) enables treatment of aortic stenosis with no need for open heart surgery. According to current guidelines, only patients considered at high surgical risk can be treated with TAVI. In this study, patient-specific analyses were performed to explore the feasibility of TAVI in morphologies, which are currently borderline cases for a percutaneous approach. Five patients were recruited: four patients with failed bioprosthetic aortic valves (stenosis) and one patient with an incompetent, native aortic valve. Three-dimensional models of the implantation sites were reconstructed from computed tomography images. Within these realistic geometries, TAVI with an Edwards Sapien stent was simulated using finite element (FE) modelling. Engineering and clinical outcomes were assessed. In all patients, FE analysis proved that TAVI was morphologically feasible. After the implantation, stress distribution showed no risks of immediate device failure and geometric orifice areas increased with low risk of obstruction of the coronary arteries. Maximum principal stresses in the arterial walls were higher in the model with native outflow tract. FE analyses can both refine patient selection and characterise device mechanical performance in TAVI, overall impacting on procedural safety in the early introduction of percutaneous heart valve devices in new patient populations.

Comparison of bare metal stenting and percutaneous pulmonary valve implantation for treatment of right ventricular outflow tract obstruction: use of an x-ray/magnetic resonance hybrid laboratory for acute physiological assessment.

Background— Treatment of right ventricular outflow tract obstruction is possible with a bare metal stent (BMS), although this treatment causes pulmonary regurgitation. In this study, we assessed the acute physiological effects of BMS versus percutaneous pulmonary valve implantation (PPVI) using an x-ray/magnetic resonance hybrid laboratory. Methods and Results— Fourteen consecutive children (median age, 12.9 years) with significant right ventricular outflow tract obstruction underwent BMS followed by PPVI. Magnetic resonance imaging (ventricular volumes and function and great vessel blood flow) and hemodynamic assessment (invasive pressure measurements) were performed before BMS, after BMS, and after PPVI; all were performed under general anesthesia in an x-ray/magnetic resonance hybrid laboratory. BMS significantly reduced the ratio of right ventricular to systemic pressure (0.75±0.17% versus 0.41±0.14%; P<0.001) with no further change after PPVI (0.42±0.11; P=1.0). However, BMS resulted in free pulmonary regurgitation (21.3±10.7% versus 41.4±7.5%; P<0.001), which was nearly abolished after PPVI (3.6±5.6%; P<0.001). Effective right ventricular stroke volume (right ventricular stroke volume minus pulmonary regurgitant volume) after BMS remained unchanged (33.8±7.3 versus 32.6±8.7 mL/m2; P=1.0) but was significantly increased after revalvulation with PPVI (41.0±8.0 mL/m2; P=0.004). These improvements after PPVI were accompanied by a significant heart rate reduction (75.5±17.7 bpm after BMS versus 69.0±16.9 bpm after PPVI; P=0.006) at maintained cardiac output (2.5±0.5 versus 2.4±0.5 versus 2.7±0.5 mL · min−1 · m−2; P=0.14). Conclusion— Using an x-ray/magnetic resonance hybrid laboratory, we have demonstrated the superior acute hemodynamic effects of PPVI over BMS in patients with right ventricular outflow tract obstruction.

Rescue surgery following percutaneous pulmonary valve implantation

OBJECTIVE Percutaneous pulmonary valve insertion (PPVI) is an evolving alternative to surgical pulmonary valve insertion. The aim of this study is to review the acute complications of PPVI requiring emergency rescue surgery. PATIENTS AND METHODS Between 09/2000 and 01/2007, 152 patients (pts), received a PPVI. Patients charts were reviewed in retrospect. RESULTS Emergency rescue surgery (ERS) took place in 6 pts (3.9%). Indications for ERS were: homograft rupture two pts, dislodgment of the stented valve in a dilated right ventricular outflow tract two pts, occlusion of the right pulmonary artery one pt and compression of the left main coronary artery one pt. Cardiopulmonary bypass was established through repeat sternotomy incision with femorofemoral cannulation in 2/6 pts. The stented valve was removed in five and replaced with a homograft in three and a valved conduit in two pts. One ruptured homograft was repaired leaving the stented valve in situ. All patients survived, one sustained mild neurological impairment. CONCLUSION Although some of the acute complications of PPVI were probably related to a learning curve (4 among the first 50 pts and 2 among the last 102 patients) the need for ERS is unlikely to be completely abolished. This experience highlights the importance of close collaboration between cardiologists and surgeons in these evolving technologies. Highly skilled and responsive surgical back up is necessary to support the introduction and to sustain institutional programmes such as PPVI.

Current approaches to pulmonary regurgitation

OBJECTIVE To evaluate the effects on ventricular function and volumes following right ventricular outflow tract reconstruction (RVOTR) with pulmonary homograft replacement (PVR) and percutaneous pulmonary valve implantation (PPVI) for predominant pulmonary regurgitation. This study was not intended to compare the two approaches. METHODS We prospectively examined 25 patients (mean age 21+/-13 years, 96% tetralogy of Fallot, 1/25 with conduit dysfunction) who had PVR with RVOTR for severe pulmonary regurgitation (PR), and 11 patients (mean age 20+/-9 years, 64% tetralogy of Fallot, 9/11 with conduit dysfunction) who underwent PPVI for predominant PR. Mean age at primary repair in both groups was 4.3+/-6.6 years. Magnetic resonance imaging was performed prior to, and 1 year following, interventions. RESULTS Before procedure, NYHA classification was similar in both groups 2.1+/-0.5. Following interventions, there was a significant reduction in RV volumes in both groups. In the surgical (PVR) group, RV end-diastolic volume (EDV) decreased from 151+/-49 to 97+/-32 ml/m(2) (p<0.0001) whereas end-systolic volume (ESV) decreased from 80+/-43 to 46+/-23 ml/m(2) (p<0.0001). In the PPVI group, RV EDV decreased from 106+/-27 to 89+/-25 ml/m(2) (p=0.002) and RV ESV from 49+/-20 to 40+/-16 ml/m(2) (p=0.034). Both groups had a significant improvement in RV (63+/-20 to 72+/-16 ml/beat, p=0.003 (PVR group), 53+/-14 to 67+/-16 ml/beat, p=0.030 (PPVI group)) and LV effective stroke volume (61+/-18 to 73+/-16 ml/beat, p=0.001 (PVR group); 59+/-24 to 75+/-16 ml/beat, p=0.009 (PPVI group)). CONCLUSIONS Following either PVR with RVOTR or PPVI, there was a significant reduction in RV volumes and an improvement in RV function. Importantly, in both groups, LV effective SV increased, and this may be the parameter to judge the benefit of the procedure. These results also support PPVI as an extra dimension in complex RVOT management.