Robert Radke

Changes in the Pacemaker Rate After Transition From Edwards SAPIEN XT to SAPIEN 3 Transcatheter Aortic Valve Implantation: The Critical Role of Valve Implantation Height.

OBJECTIVES The aim of this study was to analyze the pacemaker implantation rate (PMIR) with the new balloon-expandable Edwards SAPIEN 3 valve (S3) and the factors associated with it. BACKGROUND The introduction of the S3 for transcatheter aortic valve replacement (TAVR) has led to a reduction in paravalvular regurgitation. There are, however, concerns that the new design may increase the PMIR. METHODS The first 206 patients treated with the S3 were compared with 371 preceding patients treated with SAPIEN XT valves. Patients who previously underwent pacemaker or implantable cardioverter defibrillator implantation or transapical and valve-in-valve procedures were excluded from the analysis. All patients were monitored for at least 7 days. Previous and new conduction abnormalities were documented, and prosthesis implantation height was assessed for the S3. RESULTS There were no significant differences in baseline characteristics between groups. The PMIR was, however, significantly higher for the S3 (19.1% vs. 12.2%; p = 0.046). The mean implantation height was significantly lower in patients requiring PMI (67%/33% vs. 72%/28% aortic/ventricular stent extension, p = 0.032). On multivariate regression analysis, implantation height was the only independent predictor of PMI (odds ratio: 0.94 [95% confidence interval: 0.90 to 0.99]; p = 0.009). It increased from 68%/32% to 75%/25% when comparing the first with the second half of S3 implantations (p < 0.0001). This change was associated with a significant decrease in PMIR from 25.9% to 12.3% (p = 0.028), no longer different from the XT valve (12.2%). CONCLUSIONS The PMIR after TAVR is higher with the S3 than with the XT and is independently associated with the implantation height. This increase in the PMIR may be avoided by intending an aortic stent extension >70%.

Myocardial deformation parameters predict outcome in patients with repaired tetralogy of Fallot

Background Parameters of myocardial deformation have been suggested to be superior to conventional measures of ventricular function and to predict outcome in repaired tetralogy of Fallot (ToF). We aimed to test the hypothesis that parameters of myocardial deformation on cardiac MRI (CMR) relate to symptoms and provide prognostic information in patients with repaired ToF. Methods and results We included 372 patients with ToF (median age 16 years; 55% male), recruited within a nationwide, prospective study. Longitudinal (LS), circumferential (CS) and radial global strain (RS) were analysed by CMR-based feature tracking (FT). A combined endpoint of death, successful resuscitation or documented ventricular tachycardia was employed. Parameters of global strain were associated with New York Heart Association (NYHA) class and symptomatic deterioration. During a median follow-up of 7.4 years, 20 events occurred. Left ventricular (LV) CS and right ventricular (RV) LS emerged as predictors of outcome, independent of QRS duration, LV/RV ejection fraction and volumes, NYHA class and peak oxygen uptake. In combination, these parameters also identified a subgroup of patients at significantly increased risk of adverse of outcomes (HR 3.3, p=0.002). Furthermore, LV LS, RS, CS and RV LS were related to the risk of death and nearly missed death (p<0.05 for all). Conclusions FT-CMR provides myocardial deformation parameters, easily derived from standard CMR studies. They relate to symptoms and clinical deterioration in patients with ToF. More importantly, they predict adverse outcome independent of established risk markers, and should be considered as a useful adjunct to established outcome predictors, especially in younger patients with ToF. Clinical trial registration number http://www.clinicaltrials.gov: NCT00266188; Results.

Survival prospects of treatment naïve patients with Eisenmenger: a systematic review of the literature and report of own experience

Objectives To investigate survival in patients with Eisenmenger syndrome based on a systematic review of the literature and reanalysis of data. We specifically tested the hypothesis that previous publications have been subject to immortal time bias, confounding survival analyses. Methods A systematic review of the literature was performed to evaluate survival in treatment naïve patients with Eisenmenger syndrome and standardised mortality ratios were calculated. Furthermore, we used a contemporary cohort of 219 treatment naïve patients with Eisenmenger syndrome from the own institution as a comparison group. Results Overall, 12 studies (published 1971–2013) were identified, including a total of 1131 patients. Only one study seemed to deal appropriately with immortal time bias in this setting. All other studies did not account for this effect, thus overestimating survival prospects of patients with Eisenmenger syndrome by up to 20 years. After accounting for this effect we found high standardised mortality ratios, a 10-year mortality rate approaching 30–40% and no evidence of superior survival prospects of current era patients compared with those seen in the 1970s, 1980s and 1990s. Only, a historical Eisenmenger-cohort from the 1950s/1960s had worse survival. Conclusions The current analysis challenges the traditional view of benign survival prospects of patients with Eisenmenger syndrome. In addition, survival prospects do not seem to have considerably improved over the last decades in untreated patients. These results support a proactive treatment strategy including a more aggressive approach trying to avoid the development of the condition.

Longitudinal left ventricular 2D strain is superior to ejection fraction in predicting myocardial recovery and symptomatic improvement after aortic valve implantation

BACKGROUND Predicting improvement of myocardial function after transcatheter aortic valve implantation (TAVI) for aortic stenosis (AS) remains a challenge. As ejection fraction (EF) may be of limited value in detecting early myocardial dysfunction and predicting outcome, we assessed the potential of echocardiographic longitudinal function in this setting. MATERIALS AND METHODS Left ventricular (LV) function was assessed using EF, mitral annular plane systolic excursion (MAPSE), peak longitudinal 2D strain (LS) and strain rate (SR) in101consecutive patients with severe symptomatic AS (age 81 ± 11 years) undergoing TAVI. Echocardiography and assessment of clinical status including NYHA functional class were performed prior and after intervention (median 70 days). RESULTS Pre-interventional EF was 57 ± 17% and 32 patients (32%) had an EF<50% while 58 patients (57%) were found to have an impaired LS. After TAVI there was no significant change in EF. In contrast, LS, SR and MAPSE improved significantly (-14.0 ± 4.4 vs. -15.5 ± 4.0%; p=0.007, 0.68 ± 0.24 vs. 0.78 ± 0.23/s, p=0.002; and 9.1 ± 3.2 vs. 10.2 ± 3.3mm, p=0.006, respectively). Receiver Operating Curve characteristic analysis identified a pre-TAVI LS>-13.3% as the optimal cut-off value for predicting lack of LS recovery post TAVI. There was a marked improvement in NYHA FC after intervention (p=0.0002). Among the studied echocardiographic parameters LS change correlated closest with NYHA class improvement (r=0.42, p=0.0008). CONCLUSION Overall, LS appears to be more sensitive for detecting early myocardial damage in patients with AS compared to conventional echocardiographic parameters. More importantly, pre-interventional LS may identify irreversible myocardial dysfunction and LS improvement correlates with symptomatic improvement after intervention.

Aortic regurgitation severity after transcatheter aortic valve implantation is underestimated by echocardiography compared with MRI

Objective Aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI) is associated with a poor clinical outcome and its assessment therefore crucial. Quantification of AR by transthoracic echocardiography (TTE), however, remains challenging in this setting. The present study used quantitative flow measurement by cardiac MRI (CMR) with calculation of regurgitant fraction (RF) for the assessment of AR and compared the results with TTE. Methods and results We included 65 patients with a mean age of 82.2±8.1 years (38 women) who underwent successful TAVI with Edwards SAPIEN valves (52 transfemoral, 13 transapical). The postinterventional degree of AR was assessed by CMR and by TTE. There was agreement between CMR and TTE with regards to the absence of severe AR. However, TTE significantly underestimated the presence of moderate AR classifying it to be mild in 38 and moderate in only 5 patients, whereas CMR found mild AR in 23 and moderate in 16 patients. Overall, there was only fair agreement between CMR and TTE regarding the grading of AR with a weighted κ of 0.33. The rate of detection of TTE for more than mild AR was only 19%. Conclusions Using CMR for the quantification of AR in a sizeable group of TAVI patients, we demonstrate a strong tendency of TTE to underestimate AR compared with CMR. Since higher AR severity on echocardiography has been associated with worse patient outcome, the potential incremental prognostic value of CMR should be studied prospectively in this setting.

Diagnosis and treatment of Marfan syndrome: an update

> But in no regard was he more peculiar than in his personal appearance. He was singularly tall and thin. He stooped much. His limbs were long and emaciated. His forehead was broad and low. > “A Tale of the Ragged Mountains”, Edgar Allan Poe, 1844 Marfan syndrome (MFS) is a connective tissue disease inherited in an autosomal dominant fashion and associated with a decreased life expectancy. Skeletal features as well as a particular facial appearance are some of its most memorable features and are thought by some to be described as early as 1844 in popular literature.w1 Its earliest description in the medical literature is believed to be by Antoine-Bernard Marfan in 1896, giving the condition its name. Clinically, aortic dilatation and dissection are the most important and life threatening manifestations, but cardiac, ocular, skeletal, and neurological involvement may also impose a considerable burden. In order to facilitate diagnosis and research, expert committees published and consecutively refined a number of consensus documents: The ‘Berlin Nosology’ of 1986, the ‘Ghent Nosology’ of 1996, and more recently the ‘Revised Ghent Nosology’ of 2010. Milestones of therapy were the use of β-blockers to slow progression of aortic dilation1 and the introduction of prophylactic aortic root replacement to avoid dissection.2 Since the discovery of the conditions autosomal dominant inheritance (1931), the abnormalities of the fibrillin-1 protein (1990), and identification of pathogenic mutations in the FBN-1 gene (1991), our pathophysiological understanding has come a long way. In this article we aim to highlight some of the more recent developments in the diagnosis and treatment of MFS in adults. Owing to the multi-systemic nature of the disease, establishing the diagnosis of MFS is like piecing together a puzzle. Because aortic and cardiac complications are of foremost importance, often the cardiologist will be at the …

Value of Speckle-tracking Echocardiography and MRI-based Feature Tracking Analysis in Adult Patients after Fontan-type Palliation

BACKGROUND Patients are commonly affected by ventricular dysfunction and heart failure after Fontan palliation. Reliable quantification of ventricular function is of interest but hampered by complex ventricular anatomy and physiology. OBJECTIVES We aimed to assess myocardial function using a novel cardiac magnetic resonance imaging (CMR)-based feature-tracking (FT) technique and to study its clinical utility in Fontan patients. METHODS Retrospective study in consecutive patients attending our service. RESULTS We included 15 adult Fontan patients (age 27 ± 7 years) who underwent a standardized transthoracic echocardiographic investigation (TTE) with measurement of global strain using speckle tracking. Thirteen patients also underwent CMR, with assessment of myocardial deformation by FT, providing longitudinal and circumferential global strain for the single ventricle. The value of TTE-based strain measurements was limited by the fact that in 63% of patients at least one myocardial segment could not be adequately quantified due to limited acoustic windows. In contrast, CMR allowed for a complete visualization of all wall segments. Not surprisingly, there was poor agreement between the techniques but good or moderate interobserver variability for FT (coefficients of variability 6.6% and 14.3% for circumferential and longitudinal strain). Unlike ejection fraction, FT parameters correlated significantly with age at Fontan completion, New York Heart Association (NYHA) class, and peak oxygen uptake on cardiopulmonary exercise testing. CONCLUSIONS Assessment of myocardial function using CMR cine-based feature tracking is feasible in Fontan patients. Unlike echocardiographic techniques, FT is independent of inadequate acoustic windows and FT measurements relate to clinical parameters, suggesting that this approach could have clinical relevance in future.

Cardiac magnetic resonance feature tracking??? a novel method to assess myocardial strain: Comparison with echocardiographic speckle tracking in healthy volunteers and in patients with left ventricular hypertrophy

BACKGROUND Left ventricular longitudinal strain (LV-LS) and strain rate (SR) are sensitive markers of early systolic dysfunction. AIM To evaluate the feasibility of a novel, cardiac magnetic resonance (CMR) based method known as feature tracking (FT) for the assessment of strain and SR, and to compare the CMR based results to those obtained on standard transthoracic echocardiography (TTE) in healthy volunteers and in patients with left ventricular hypertrophy cardiomyopathy (HCM). METHODS Overall, 20 healthy volunteers (ten male, mean age 24 ± 3 years) and 20 consecutive patients with HCM (12 male, mean age 47 ± 19 years) were included. Longitudinal and circumferential strain and SR of the left ventricle were measured on CMR at 1.5 Tesla and TTE and interobserver variability was assessed. RESULTS FT measurements were feasible in all subjects. A good agreement between global LV-LS measured on CMR (controls: 20.8 ± 3.0; HCM: 17.6 ± 3.8) and TTE (controls: 19.4 ± 2.1; HCM: 16.6 ± 2.9) was found, while the agreement was worse for circumferential strain and all SR measurements. For the left and right ventricles, interobserver reproducibility was higher for strain measurements compared to SR. Coefficients of variation were lowest for LV-LS (13.2%) by CMR. CONCLUSIONS FT analysis is a novel CMR based method for the analysis of myocardial strain and SR that is simple and correlates well with the echocardiographic measurements. Since CMR is unaffected by inadequate acoustic windows, FT may represent an attractive alternative to echocardiography in assessing the increasingly important parameters of myocardial deformation.

Analysis of associations between congenital heart defect complexity and health-related quality of life using a meta-analytic strategy

BACKGROUND As a consequence of heterogeneous results of relatively small individual trials, the impact of congenital heart defects (CHD) and the effect of disease severity on patient reported outcome measures (PROs) of quality of life (QoL) remains uncertain. We aimed to systematically summarize QoL data in CHD patients using meta-analytic methods. METHODS AND RESULTS We performed a systematic review of the literature focusing on QoL in CHD. The search yielded 234 publications meeting the inclusion criteria, with a median of 88 patients per study (46% females, average age 24years). In total, QoL was reported using PROs in 47,471 CHD-patients. More than 95 different PROs were used to evaluate QoL. The most commonly used tool was the SF36 form (69 publications). Analysis of available quantitative QoL data from SF36 publications (n=4217 CHD patients) showed that QoL was reduced in patients with moderate or complex cardiac disease (e.g. relative physical functioning scores 0.96 [0.93-0.99] and 0.91 [0.88-0.95] compared with controls), while no such effect was evident in those patients with simple cardiac lesions. Similar results were found for the general health domain of the SF36 domain. CONCLUSIONS Despite the proliferation of QoL-studies in CHD no standardized approach for measuring and reporting QoL has emerged and the published results are heterogeneous. In aggregation, however, the results of this study suggest that QoL is impaired in moderate or complex CHD, while no such impact of CHD on QoL could be established--on average--in patients with simple defects.

Endothelial function in contemporary patients with repaired coarctation of aorta

Objective Previous studies have suggested endothelial dysfunction in adult patients after repair of aortic coarctation (CoA). It has been proposed to play a key role in the pathogenesis of arterial hypertension in the absence of re-coarctation. We aimed to assess the presence of endothelial dysfunction, the number of endothelial progenitor cells (EPC), and the levels of proinflammatory cytokines associated with endothelial injury in contemporary patients after CoA repair. Methods For this prospective observational study, 20 CoA patients and 22 healthy controls were recruited. Digital reactive hyperaemia was measured by peripheral arterial tonometry. Flow cytometry was used to quantify EPCs, and a comprehensive panel of laboratory markers of endothelial dysfunction was measured. Results Half the patients had known arterial hypertension requiring medical treatment. Indices of reactive hyperaemia showed no significant difference between CoA patients (1.96±0.32) and controlss (1.765±0.48) (p=0.82). Circulating EPCs, defined by the number of CD34+, CD34+/KDR+, CD34+/AC133+, CD34+/AC133+/KDR+ or CD34+/CD45− labelled cells were equally not significantly different between the groups. Furthermore, plasma levels of inflammatory mediators and markers of endothelial function (IL-6, IL-8, ICAM1 and VCAM1) were not significantly different between the groups, as were vascular endothelial growth factor levels (p>0.05, for all). Conclusions By contrast with earlier reports, no clinically significant difference in endothelial function between adult patients with coarctation repair and healthy controls could be demonstrated. Therefore, endothelial dysfunction may not necessarily be present in this population. Further studies are required to identify mechanisms and to develop strategies to avoid arterial hypertension in these patients.