Abstract: OBJECTIVE: To analyse the potential benefit of restoration of pulmonary valvar competence in patients with severe pulmonary regurgitation (PR) and pulmonary hypertension (PH) associated with congenital heart disease. DESIGN: Retrospective study. SETTING: Tertiary paediatric and adult congenital heart cardiac centre. INTERVENTIONS: Percutaneous pulmonary valve implantation (PPVI). PATIENTS: All patients who underwent PPVI for treatment of PR in the presence of PH (mean PAP >25 mm Hg). RESULTS: Seven patients with severe PH as a result of congenital heart disease and severe PR underwent PPVI. The valve implantation procedure was feasible and uncomplicated in all seven cases, successfully abolishing PR. There was a significant increase in diastolic (15.4 (7.3) to 34.0 (8.5) mm Hg; p = 0.007) and mean (29.7 (8.1) to 41.3 (12.9) mm Hg; p = 0.034) pulmonary artery pressures, and an improvement in NYHA functional class (from median IV to median III; p<0.008). Peripheral oxygen saturations rose from 85.9% (11.0%) to 91.7% (8.3%) (p = 0.036). Right ventricular (RV) volumes decreased (from 157.0 (44.7) to 140.3 (53.3) ml/m(2)), while effective RV stroke volume increased (from 23.4 (9.3) to 41.0 (11.6) ml/m(2)). During a median follow-up of 20.3 months (range 1.3-47.5), valvar competence was well maintained despite near systemic pulmonary pressures. None of the valved stents were explanted during follow-up. CONCLUSION: Trans-catheter treatment of PR in patients with PH is well tolerated and leads to clinical and haemodynamic improvement, most probably caused by a combination of increased pulmonary perfusion pressures and RV efficiency.
Abstract: Percutaneous pulmonary valve implantation helps in prolonging the lifespan of surgically placed right ventricle-to-pulmonary artery (RV-PA) conduits, and represents a less invasive alternative to repeat open-heart surgery. The clinical indications for treatment match those of surgery. As far as the suitability is concerned, the current ideal substrate is a degenerated RV-PA conduit, because of the presence of a certain degree of calcification that offers a safe anchoring point. So far, patients have been treated with low morbidity and mortality that were further improved with increasing experience. After percutaneous pulmonary valve implantation, patients experience a subjective improvement, mirrored by an objective increase of measured exercise capacity parameters and by reduced RV-PA gradient, regurgitant fraction, and RV volumes. New developments in the experimental field should result in an extension of indications in the future.
Abstract: OBJECTIVE: The Ross procedure offers good autograft function and low reoperation rates for the neoaortic valve; however, the rate of conduit dysfunction in the right ventricular outflow tract remains a concern. This study assessed percutaneous pulmonary valve implantation in this setting. METHODS: We retrospectively analyzed outcomes of 12 patients (mean age 28 +/- 5 years) referred for percutaneous pulmonary valve implantation to treat right ventricle-pulmonary artery conduit failure 11.1 +/- 3.3 years after Ross procedure. RESULTS: Percutaneous pulmonary valve implantation was feasible in all 12 patients, with no procedural complications (procedure time 99 +/- 16 minutes, fluoroscopy time 21 +/- 6 minutes). Right ventricular outflow tract gradient during catheterization and pulmonary regurgitant fraction on magnetic resonance imaging fell after valve implantation (gradient 34 +/- 6 to 14 +/- 3 mm Hg, P < .01, regurgitant fraction 20% +/- 6% to 2% +/- 1%, P < .05). After restoration of right ventricular outflow tract function, indexed right ventricular end-diastolic volume decreased (91 +/- 13 to 78 +/- 12 mL x beat(-1) x m(-2), P < .01) and maximal cardiopulmonary exercise performance improved (peak oxygen consumption 25.4 +/- 2.3 to 30.8 +/- 3.0 mL x kg(-1) x min(-1), P < .01). During follow-up (18.8 +/- 4.6 months), there was 1 device explantation (restenosis). The probabilities of freedom from right ventricular outflow tract reoperation were 100% at 1 year and 90% at 3 years. CONCLUSIONS: Percutaneous pulmonary valve implantation provides an effective transcatheter treatment strategy to prolong the lifespan of right ventricle-pulmonary artery conduits after the Ross procedure, reducing the reoperation burden on patients with aortic valve disease.
Abstract: PURPOSE: To assess the feasibility and reproducibility of real-time radial k-t sensitivity encoding (SENSE) magnetic resonance imaging (MRI) for biventricular volumetric assessment during exercise. MATERIALS AND METHODS: In all, 12 healthy young adults underwent MRI at rest and during supine exercise at three different workload intensities. Biventricular volumes and function were assessed with 1) a radial k-t SENSE real-time sequence and 2) a scanner vendor supplied (standard) real-time sequence. Global image quality, motion fidelity, and agreement in right ventricular (RV) and left ventricular (LV) stroke volume (SV) as a surrogate measure for accuracy were assessed. Exercise MR was repeated within 1 month for assessment of reproducibility. RESULTS: Imaging scores were superior for radial real-time k-t SENSE images (P < 0.001). Agreement in RV and LV SV during exercise was better with radial k-t real-time (SD of difference +/-3.43 vs. +/-8.97 mL; P < 0.001). Agreement in cardiac output (CO) in the same subject at two different imaging sessions was better for radial k-t SENSE. This was significant for the CO calculated for the RV (SD of difference +/-0.6 vs. +/-0.95 L/min; P = 0.01) and LV (+/-0.45 vs. +/-0.92 L/min; P < 0.001). CONCLUSION: Radial k-t SENSE real-time imaging represents a feasible and reproducible imaging technique for biventricular assessment during exercise.
Abstract: 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 x min(-1) x m(-2); P=0.14). CONCLUSIONS: 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.
Abstract: 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.
Abstract: OBJECTIVE: To assess autograft, homograft and ventricular function, as well as exercise capacity, in adult patients who have undergone the Ross procedure. SETTING: Single centre paediatric and adult congenital heart disease unit. PATIENTS: 45 subjects (24.6y, range 16.9-52.2y) who underwent the Ross procedure between 1994 and 2006 (8.1y post Ross operation, range 2.0-14.0y). INTERVENTIONS: Cardiovascular magnetic resonance imaging, echocardiography and cardiopulmonary exercise testing. MAIN OUTCOME MEASURES: Autograft and homograft stenosis, and regurgitation. Autograft size. Bi-ventricular function, scar volume and exercise capacity. RESULTS: Mean autograft regurgitation was 6.8+/-8.3% (trivial regurgitation) and diameter was 40.0+/-7.0mm. Mean homograft velocity was 2.4+/-0.6m/s (mild-moderate stenosis) and regurgitation was 6.1+/-8.3% (trivial regurgitation). Biventricular systolic function was normal (LV EF 63.1+/- 6.4% and RV EF 60.1+/- 7.6%). In 38% of cases there was evidence of LV scar, mostly noted within the inter-ventricular septum. The mean exercise capacity achieved was 87+/- 22% of predicted. There was no correlation between exercise capacity and ventricular function or scar. CONCLUSION: This study demonstrates minor autograft and homograft dysfunction in the majority of patients post Ross procedure, associated with good ventricular function and exercise capacity. In addition, minor scar was present in a third of patients with no functional consequences.
Abstract: AIMS: To prospectively evaluate homograft function with cardiac magnetic resonance (CMR) imaging 1 year after insertion into the pulmonary position, and to assess the impact of in situ homograft geometry, surgical factors, and 'intrinsic' homograft properties on early valve incompetence. METHODS AND RESULTS: A total of 60 patients (mean age 21 +/- 10 years; 35 females) with congenital heart disease underwent pulmonary valve replacement with homograft insertion and were prospectively enrolled into a study protocol that included serial echocardiography and CMR 1 year after surgery. None of the patients had homograft stenosis but 10 (17%) had significant homograft incompetence (i.e. pulmonary regurgitation fraction >20% on CMR). A higher incidence of 'eccentric' pulmonary forward flow pattern (P < 0.001, Fisher's exact test), more acute 'homograft distortion angle' (P < 0.001), larger relative 'annular' size (P < 0.01), and greater pre-homograft right ventricular outflow tract (RVOT) diameters (P = 0.01) at CMR was seen in those with worse homograft function. In a backward multivariate linear regression model, 'eccentric' pulmonary forward flow pattern (r(part) = 0.36, P < 0.001), 'homograft distortion angle' (r(part) = 0.31, P = 0.001), and pre-homograft RVOT diameter (r(part) = 0.19, P = 0.03) were independently associated with the degree of pulmonary regurgitation (in %) at 1 year. CONCLUSION: Using CMR, in this prospective cohort study, we have shown that significant valve incompetence is present in one-sixth of patients after homograft insertion into the pulmonary position, and that alterations in the in situ homograft geometry were associated with the likelihood of developing valve incompetence. These findings imply that mechanical factors may have an important impact on homograft performance.
Abstract: 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. Patient's 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.
Abstract: AIMS: Percutaneous pulmonary valve implantation (PPVI) is now an accepted treatment strategy for right ventricular (RV) outflow tract (RVOT) dysfunction in many European Heart Centres. We analysed the efficacy of repeat PPVI as a treatment modality for early device failure. METHODS AND RESULTS: Twenty patients underwent repeat PPVI for RVOT obstruction because of early device failure ('Hammock effect', 'Hammock-like effect', stent fracture, residual stenosis). Repeat PPVI was feasible in all patients with no procedural complications. Following implantation of a second device, catheter-measured RVOT gradient and RV systolic pressure fell significantly (RVOT gradient: 46.1 +/- 3.9 to 18.1 +/- 2.4 mmHg, P < 0.001; RVSP: 70.9 +/- 4.8 to 46.1 +/- 2.6 mmHg, P < 0.001), in all but one patient (15 years, male, common arterial trunk, 11.5 mm homograft). During follow-up, four of 20 required re-intervention [third PPVI for stent fracture (n = 2), device explantation: external compression by the sternum (n = 1), endocarditis (n = 1)], and one of the 20 is awaiting surgical management. In the remainder, second PPVI resulted in a sustained improvement in haemodynamics with a mean follow-up of 10.9 +/- 3.0 months. In this series, the probability of freedom from re-intervention at 2 years was higher after second PPVI when compared with the index procedure (89.4 vs. 20.0%, P < 0.001). CONCLUSION: Repeat PPVI is an effective treatment for early device failure in defined conditions and leads to improved freedom from re-intervention.
Abstract: 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.
Abstract: 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.
Abstract: Percutaneous transcatheter intervention for valvular heart disease is the new horizon in transcatheter therapeutics. Balloon dilatation has been used successfully for treatment of congenital and acquired stenotic lesions of semilunar and atrio-ventricular valves. Although attempts have been made to repair and replace cardiac valves without cardiopulmonary bypass and through percutaneous techniques, this has only recently become a reality. The semilunar valves have preceded atrioventricular valves in successful application in animals and humans. Morphological features play an important role in determining the design of the valve and technique and site of implantation. The major deviations in research and development in artificial or tissue valves have included attempts at delivery of these valves to the site of implantation without open heart surgery. Successful implantation needs long-term follow-up for the durability of the valve and freedom from re-intervention.
Abstract: 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. CONCLUSIONS: 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.
Abstract: OBJECTIVES: To analyze factors responsible for stent fracture in percutaneous pulmonary valve implantation (PPVI) by finite element method. BACKGROUND: PPVI is an interventional catheter-based technique for treating significant pulmonary valve disease. Stent fracture is a recognized complication. METHODS: Three different stent models were created: (1) platinum-10% iridium alloy stent - resembles the first-generation PPVI device; (2) same geometry, but with the addition of gold over the strut intersections - models the current stent; (3) same design as 1, but made of thinner wire. For Model 3, a stent-in-stent solution was applied. Numerical analyses of the deployment of these devices were performed to understand the stress distribution and hence stent fracture potential. RESULTS: Model 1: Highest stresses occurred at the strut intersections, suggesting that this location may be at highest risk of fracture. This concurs with the in vivo stent fracture data. Model 2: Numerical analyses indicate that the stresses are lower at the strut intersections, but redistributed to the end of the gold reinforcements. This suggests that fractures in this device may occur just distal to the gold. This is indeed the clinical experience. Model 3 was weakest at bolstering the implantation site; however, when two stents were coupled (stent-in-stent technique), better strength and lower stresses were seen compared with Model 1 alone. CONCLUSIONS: Using finite element analysis of known stents, we were able to accurately predict stent fractures in the clinical situation. Furthermore, we have demonstrated that a stent-in-stent technique results in better device performance, which suggests a novel clinical strategy.
Abstract: Clinical and animal studies suggest that estrogen receptors are involved in the development of myocardial hypertrophy and heart failure. In this study, we investigated whether human myocardial estrogen receptor alpha (ERalpha) expression, localization, and association with structural proteins was altered in end stage-failing hearts. We found a 1.8-fold increase in ERalpha mRNA and protein in end-stage human dilated cardiomyopathy (DCM, n=41), as compared with controls (n=25). ERalpha was visualized by confocal immunofluorescence microscopy and localized to the cytoplasm, sarcolemma, intercalated discs and nuclei of cardiomyocytes. Immunofluorescence studies demonstrated colocalization of ERalpha with beta-catenin at the intercalated disc in control hearts and immunoprecipitation studies confirmed complex formation of both proteins. Interestingly, the ERalpha/beta-catenin colocalization was lost at the intercalated disc in DCM hearts. Thus, the ERalpha/beta-catenin colocalization in the intercalated disc may be of functional relevance and a loss of this association may play a role in the progression of heart failure. The increase of total ERalpha expression may represent a compensatory process to contribute to the stability of cardiac intercalated discs.
Abstract: Transcatheter valve replacement has recently been introduced into clinical practice and has the potential to transform the management of valvular heart disease. To date, the largest human experience exists with percutaneous pulmonary valve implantation in patients with repaired congenital heart disease who require re-intervention to the right ventricular outflow tract. The application of this approach, however, is presently restricted to certain right ventricular outflow tract morphologies, because the device needs to be anchored safely to prevent device dislodgement. Early results of percutaneous pulmonary valve implantation show lower morbidity than surgery and significant early symptomatic improvement. In the future, the challenge will be to extend percutaneous pulmonary valve implantation to all patients with a clinical indication to delay or avoid repeat open-heart surgery.
Abstract: 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-alpha and -beta, calcineurin A-beta, 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-alpha 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-beta mRNA was increased 2.6-fold in patients with aortic valve stenosis (P<0.0001). ER-alpha and -beta were found in the cytoplasm and nuclei of human hearts. A strong inverse correlation exists between ER-beta and calcineurin A-beta mRNA in patients with aortic valve stenosis (r=-0.83, P=0.002) but not between ER-alpha or -beta and BNP mRNA. CONCLUSIONS: ER-alpha and -beta in the human heart are upregulated by myocardial pressure load.
