Philipp Lurz

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.

Diagnostic Performance of CMR Imaging Compared With EMB in Patients With Suspected Myocarditis

OBJECTIVES The goal of this study was to assess the diagnostic performance of cardiac magnetic resonance (CMR) compared with endomyocardial biopsy in patients with suspected acute myocarditis (AMC) and chronic myocarditis (CMC). BACKGROUND Several studies have reported an encouraging diagnostic performance of CMR in myocarditis. However, the comparison of CMR with clinical data only and the use of preselected patient populations are important limitations of the majority of these reports. METHODS One hundred thirty-two consecutive patients with suspected AMC (defined by symptoms ≤ 14 days; n = 70) and CMC (defined by symptoms >14 days; n = 62) were included. Patients underwent cardiac catheterization with left ventricular endomyocardial biopsy and CMR, including T(2)-weighted imaging for assessment of edema, T(1)-weighted imaging before and after contrast administration for evaluation of hyperemia, and assessment of late gadolinium enhancement. CMR results were considered to be consistent with the diagnosis of myocarditis if 2 of 3 CMR techniques were positive. RESULTS Within the total population, myocarditis was the most common diagnosis on endomyocardial biopsy analysis (62.9%). Viral genomes were detected in 30.3% (40 of 132) of patients within the total patient population and significantly more often in patients with AMC than CMC (40.0% vs. 19.4%; p = 0.013). For the overall cohort of patients with either suspected AMC or CMC, the diagnostic sensitivity, specificity, and accuracy of CMR were 76%, 54%, and 68%, respectively. The best diagnostic performance was observed in patients with suspected AMC (sensitivity, 81%; specificity, 71%; and accuracy, 79%). In contrast, diagnostic performance of CMR in suspected CMC was found to be unsatisfactory (sensitivity, 63%; specificity, 40%; and accuracy, 52%). CONCLUSIONS The results of this study underline the usefulness of CMR in patients with suspected AMC. In contrast, the diagnostic performance of CMR in patients with suspected CMC might not be sufficient to guide clinical management.

Randomized Sham-Controlled Trial of Renal Sympathetic Denervation in Mild Resistant Hypertension

Few data are available with regard to the effectiveness of renal sympathetic denervation in patients with resistant hypertension yet only mildly elevated blood pressure (BP). Patients with resistant hypertension and slightly elevated BP (day-time systolic pressure, 135–149 and diastolic pressure, 90–94 mm Hg on 24-hour ambulatory measurement) were randomized in a 1:1 ratio to renal sympathetic denervation with the Symplicity Flex Catheter (Medtronic) or an invasive sham procedure. The primary efficacy end point was the change in 24-hour systolic BP at 6 months between groups in the intention to treat population. A total of 71 patients underwent randomization. Baseline day-time systolic BP was 144.4±4.8 mm Hg in patients assigned to denervation and 143.0±4.7 mm Hg in patients randomized to the sham procedure. The mean change in 24-hour systolic BP in the intention to treat cohort at 6 months was −7.0 mm Hg (95% confidence interval, −10.8 to −3.2) for patients undergoing denervation and −3.5 mm Hg (95% confidence interval, −6.7 to −0.2) in the sham group (P=0.15). In the per protocol population, the change in 24-hour systolic BP at 6 months was −8.3 mm Hg (95% confidence interval, −11.7 to −5.0) for patients undergoing denervation and −3.5 mm Hg (95% confidence interval, −6.8 to −0.2) in the sham group (P=0.042). In patients with mild resistant hypertension, renal sympathetic denervation failed to show a significant reduction in the primary end point of 24-hour systolic BP at 6 months between groups in the intention to treat analysis. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01656096.

Comprehensive Cardiac Magnetic Resonance Imaging in Patients With Suspected Myocarditis: The MyoRacer-Trial.

BACKGROUND Data suggest that T1 and T2 mapping have excellent diagnostic accuracy in patients with suspected myocarditis. However, the true diagnostic performance of comprehensive cardiac magnetic resonance (CMR) mapping versus endomyocardial biopsy (EMB) has not been determined. OBJECTIVES This study assessed the performance of CMR imaging, including T1 and T2 mapping, compared with EMB in an unselected, consecutive patient cohort with suspected myocarditis. It also examined the potential role of CMR field strength by comparing 1.5-T versus 3.0-T imaging. METHODS Patients underwent biventricular EMB, cardiac catheterization (for exclusion of coronary artery disease), and CMR imaging on 1.5- and 3-T scanners. The CMR protocol included current standard Lake Louise criteria (LLC) for myocarditis as well as native T1, calculation of extracellular volume fraction (ECV), and T2 mapping (only on 1.5-T). Patients were divided into 2 groups according to symptom duration (acute: ≤14 days vs. chronic: >14 days). RESULTS A total of 129 patients underwent 1.5-T imaging. In patients with acute symptoms, native T1 yielded the best diagnostic performance as defined by the area under the curve (AUC) of receiver-operating curves (0.82) followed by T2 (0.81), ECV (0.75), and LLC (0.56). In patients with chronic symptoms, only T2 mapping yielded an acceptable AUC (0.77). On 3.0-T, AUCs of native T1, ECV, and LLC were comparable to 1.5-T with no significant differences. CONCLUSIONS In patients with acute symptoms, mapping techniques provide a useful tool for confirming or rejecting the diagnosis of myocarditis and are superior to the LLC. However, only T2 mapping has acceptable diagnostic performance in patients with chronic symptoms. (Magnetic Resonance Imaging in Myocarditis [MyoRacer]; NCT02177630).

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.

Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial

BACKGROUND Previous randomised renal denervation studies did not show consistent efficacy in reducing blood pressure. The objective of our study was to evaluate the effect of renal denervation on blood pressure in the absence of antihypertensive medications. METHODS SPYRAL HTN-OFF MED was a multicentre, international, single-blind, randomised, sham-controlled, proof-of-concept trial. Patients were enrolled at 21 centres in the USA, Europe, Japan, and Australia. Eligible patients were drug-naive or discontinued their antihypertensive medications. Patients with an office systolic blood pressure (SBP) of 150 mm Hg or greater and less than 180 mm Hg, office diastolic blood pressure (DBP) of 90 mm Hg or greater, and a mean 24-h ambulatory SBP of 140 mm Hg or greater and less than 170 mm Hg at second screening underwent renal angiography and were randomly assigned to renal denervation or sham control. Patients, caregivers, and those assessing blood pressure were blinded to randomisation assignments. The primary endpoint, change in 24-h blood pressure at 3 months, was compared between groups. Drug surveillance was done to ensure patient compliance with absence of antihypertensive medication. The primary analysis was done in the intention-to-treat population. Safety events were assessed at 3 months. This study is registered with ClinicalTrials.gov, number NCT02439749. FINDINGS Between June 25, 2015, and Jan 30, 2017, 353 patients were screened. 80 patients were randomly assigned to renal denervation (n=38) or sham control (n=42) and followed up for 3 months. Office and 24-h ambulatory blood pressure decreased significantly from baseline to 3 months in the renal denervation group: 24-h SBP -5·5 mm Hg (95% CI -9·1 to -2·0; p=0·0031), 24-h DBP -4·8 mm Hg (-7·0 to -2·6; p<0·0001), office SBP -10·0 mm Hg (-15·1 to -4·9; p=0·0004), and office DBP -5·3 mm Hg (-7·8 to -2·7; p=0·0002). No significant changes were seen in the sham-control group: 24-h SBP -0·5 mm Hg (95% CI -3·9 to 2·9; p=0·7644), 24-h DBP -0·4 mm Hg (-2·2 to 1·4; p=0·6448), office SBP -2·3 mm Hg (-6·1 to 1·6; p=0·2381), and office DBP -0·3 mm Hg (-2·9 to 2·2; p=0·8052). The mean difference between the groups favoured renal denervation for 3-month change in both office and 24-h blood pressure from baseline: 24-h SBP -5·0 mm Hg (95% CI -9·9 to -0·2; p=0·0414), 24-h DBP -4·4 mm Hg (-7·2 to -1·6; p=0·0024), office SBP -7·7 mm Hg (-14·0 to -1·5; p=0·0155), and office DBP -4·9 mm Hg (-8·5 to -1·4; p=0·0077). Baseline-adjusted analyses showed similar findings. There were no major adverse events in either group. INTERPRETATION Results from SPYRAL HTN-OFF MED provide biological proof of principle for the blood-pressure-lowering efficacy of renal denervation. FUNDING Medtronic.

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.

Extracellular Volume Fraction for Characterization of Patients With Heart Failure and Preserved Ejection Fraction.

BACKGROUND Optimal patient characterization in heart failure with preserved ejection fraction (HFpEF) is essential to tailor successful treatment strategies. Cardiac magnetic resonance (CMR)-derived T1 mapping can noninvasively quantify diffuse myocardial fibrosis as extracellular volume fraction (ECV). OBJECTIVES This study aimed to elucidate the diagnostic performance of T1 mapping in HFpEF by examining the relationship between ECV and invasively measured parameters of diastolic function. It also investigated the potential of ECV to differentiate among pathomechanisms in HFpEF. METHODS We performed T1 mapping in 24 patients with HFpEF and 12 patients without heart failure symptoms. Pressure-volume loops were obtained with a conductance catheter during basal conditions and handgrip exercise. Transient pre-load reduction was used to extrapolate the diastolic stiffness constant. RESULTS Patients with HFpEF showed higher ECV (p < 0.01), elevated load-independent passive left ventricular (LV) stiffness constant (beta) (p < 0.001), and a longer time constant of active LV relaxation (p = 0.02). ECV correlated highly with beta (r = 0.75; p < 0.001). Within the HFpEF cohort, patients with ECV greater than the median showed a higher beta (p = 0.05), whereas ECV below the median identified patients with prolonged active LV relaxation (p = 0.01) and a marked hypertensive reaction to exercise due to pathologic arterial elastance (p = 0.04). On multiple linear regression analyses, ECV independently predicted intrinsic LV stiffness (β = 0.75; p < 0.01). CONCLUSIONS Diffuse myocardial fibrosis, assessed by CMR-derived T1 mapping, independently predicts invasively measured LV stiffness in HFpEF. Additionally, ECV helps to noninvasively distinguish the role of passive stiffness and hypertensive exercise response with impaired active relaxation. (Left Ventricular Stiffness vs. Fibrosis Quantification by T1 Mapping in Heart Failure With Preserved Ejection Fraction [STIFFMAP]; NCT02459626).