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Featured researches published by Titus Kuehne.


Circulation | 2004

Magnetic Resonance Imaging Analysis of Right Ventricular Pressure-Volume Loops In Vivo Validation and Clinical Application in Patients With Pulmonary Hypertension

Titus Kuehne; Sevim Yilmaz; Paul Steendijk; Phillip Moore; Maarten Groenink; Maythem Saaed; Oliver M. Weber; Charles B. Higgins; Peter Ewert; Eckard Fleck; Eike Nagel; Ingram Schulze-Neick; Peter E. Lange

Background—The aims of this study were to validate MRI-derived right ventricular (RV) pressure-volume loops for assessment of RV myocardial contractility and then to apply this technique in patients with chronic RV pressure overload for assessment of myocardial contractility, ventricular pump function, and VA coupling. Methods and Results—Flow-directed catheters were guided under MR fluoroscopy (1.5 T) into the RV for invasive pressure measurements. Simultaneously, ventricular volumes and myocardial mass were assessed from cine MRI. From sampled data, RV pressure-volume loops were constructed, and maximal ventricular elastance indexed to myocardial mass (Emax_i) was derived by use of a single-beat estimation method. This MRI method was first validated in vivo (6 swine), with conductance techniques used as reference. Bland-Altman test showed good agreement between methods (Emax_i=5.1±0.5 versus 5.8±0.7 mm Hg · mL−1 · 100 g−1, respectively; P=0.08). Subsequently, the MRI method was applied in 12 subjects: 6 control subjects and 6 patients with chronic RV pressure overload from pulmonary hypertension. In these patients, indexes of RV pump function (cardiac index), Emax_i, and VA coupling (Emax/Ea) were assessed. In patients with pulmonary hypertension, RV pump function was decreased (cardiac index, 2.2±0.5 versus 2.9±0.4 L · min−1 · m−2; P<0.01), myocardial contractility was enhanced (Emax_I, 9.2±1.1 versus 5.0±0.9 mm Hg · mL−1 · 100 g−1; P<0.01), and VA coupling was inefficient (Emax/Ea, 1.1±0.3 versus 1.9±0.4; P<0.01) compared with control subjects. Conclusions—RV myocardial contractility can be determined from MRI-derived pressure-volume loops. Chronic RV pressure overload was associated with reduced RV pump function despite enhanced RV myocardial contractility. The proposed MRI approach is a promising tool to assess RV contractility in the clinical setting.


European Heart Journal | 2011

Percutaneous pulmonary valve implantation: two-centre experience with more than 100 patients

Andreas Eicken; Peter Ewert; Alfred Hager; Bjoern Peters; Sohrab Fratz; Titus Kuehne; Raymonde Busch; John Hess; Felix Berger

AIMS Dysfunction of valved conduits in the right ventricular outflow tract (RVOT) limits durability and enforces repeated surgical interventions. We report on our combined two-centre experience with percutaneous pulmonary valve implantation (PPVI). METHODS AND RESULTS One hundred and two patients with RVOT dysfunction [median weight: 63 kg (54.2-75.9 kg), median age: 21.5 years (16.2-30.1 years), diagnoses: TOF/PA 61, TAC 14, TGA 9, other 10, AoS post-Ross-OP 8] were scheduled for PPVI since December 2006. Percutaneous pulmonary valve implantation was performed in all patients. Pre-stenting of the RVOT was done in 97 patients (95%). The median peak systolic RVOT gradient decreased from 37 mmHg (29-46 mmHg) to 14 mmHg (9-17 mmHg, P < 0.001) and the ratio RV pressure/AoP decreased from 62% (53-76%) to 36% (30-42%, P < 0.0001). The median end-diastolic RV-volume index (MRI) decreased from 106 mL/m(2) (93-133 mL/m(2)) to 90 mL/m(2) (71-108 mL/m(2), P = 0.001). Pulmonary regurgitation was significantly reduced in all patients. One patient died due to compression of the left coronary artery. The incidence of stent fractures was 5 of 102 (5%). During follow-up [median: 352 days (99-390 days)] one percutaneous valve had to be removed surgically 6 months after implantation due to bacterial endocarditis. In 8 of 102 patients, a repeated dilatation of the valve was done due to a significant residual systolic pressure gradient, which resulted in a valve-in-valve procedure in four. CONCLUSION This study shows that PPVI is feasible and it improves the haemodynamics in a selected patient collective. Apart from one coronary compression, the rate of complications at short-term follow-up was low. Percutaneous pulmonary valve implantation can be performed by experienced interventionalists with similar results as originally published. The intervention is technically challenging and longer clinical follow-up is needed.


Circulation | 2015

Pediatric Pulmonary Hypertension Guidelines From the American Heart Association and American Thoracic Society

Steven H. Abman; Georg Hansmann; Stephen L. Archer; D. Dunbar Ivy; Ian Adatia; Wendy K. Chung; Brian D. Hanna; Erika B. Rosenzweig; J. Usha Raj; David N. Cornfield; Kurt R. Stenmark; Robin H. Steinhorn; Bernard Thébaud; Jeffrey R. Fineman; Titus Kuehne; Jeffrey A. Feinstein; Mark K. Friedberg; Michael G. Earing; Robyn J. Barst; Roberta L. Keller; John P. Kinsella; Mary P. Mullen; Robin Deterding; Thomas J. Kulik; George B. Mallory; Tilman Humpl; David L. Wessel

Pulmonary hypertension is associated with diverse cardiac, pulmonary, and systemic diseases in neonates, infants, and older children and contributes to significant morbidity and mortality. However, current approaches to caring for pediatric patients with pulmonary hypertension have been limited by the lack of consensus guidelines from experts in the field. In a joint effort from the American Heart Association and American Thoracic Society, a panel of experienced clinicians and clinician-scientists was assembled to review the current literature and to make recommendations on the diagnosis, evaluation, and treatment of pediatric pulmonary hypertension. This publication presents the results of extensive literature reviews, discussions, and formal scoring of recommendations for the care of children with pulmonary hypertension.


Circulation-cardiovascular Imaging | 2010

Sex-Specific Pediatric Percentiles for Ventricular Size and Mass as Reference Values for Cardiac MRI Assessment by Steady-State Free-Precession and Phase-Contrast MRI Flow

Samir Sarikouch; Brigitte Peters; Matthias Gutberlet; Birte Leismann; Andrea Kelter-Kloepping; Hermann Koerperich; Titus Kuehne; Philipp Beerbaum

Background— Cardiac MRI is important in the treatment of children with congenital heart disease, but sufficient normative data are lacking. For ventricular volumes and mass, we sought to deliver reference centiles and to investigate sex effects. Methods and Results— We included 114 healthy children and adolescents, uniformly distributed spanning an age range of 4 to 20 years, as required by the Lambda-Mu-Sigma method to achieve a percentile distribution, thus avoiding arbitrary age categories. Subjects underwent axial volumetry (1.5-T scanner) using standardized 2D steady-state free-precession and flow protocols. Percentiles were computed for age 8 to 20 years (99 subjects) because breath-holds were more consistent in this group. When indexed for body surface area or height, the centile curves of ventricular volumetric parameters showed allometric increase until adolescence, when a plateau was reached, with values comparable to published adult reference data. In contrast, ventricular mass centiles increased without plateau. There was a significant sex difference, with centiles reflecting larger values in boys than in girls ( P <0.05) when ventricular volumes were indexed to body surface area or height but not when indexed to weight (exception: mass). There was excellent agreement of axial and short-axis volumetry and of volumetric and flow-derived stroke volumes. Conclusions— Percentiles for ventricular volumes and mass in healthy children have been established to serve as reference values in pediatric heart disease. Significant sex differences were noted when indexing volumes to body surface area or height. Unisex centiles related to weight may be considered for chamber volumes albeit not for mass. Received February 19, 2009; accepted October 1, 2009. # CLINICAL PERSPECTIVE {#article-title-2}Background—Cardiac MRI is important in the treatment of children with congenital heart disease, but sufficient normative data are lacking. For ventricular volumes and mass, we sought to deliver reference centiles and to investigate sex effects. Methods and Results—We included 114 healthy children and adolescents, uniformly distributed spanning an age range of 4 to 20 years, as required by the Lambda-Mu-Sigma method to achieve a percentile distribution, thus avoiding arbitrary age categories. Subjects underwent axial volumetry (1.5-T scanner) using standardized 2D steady-state free-precession and flow protocols. Percentiles were computed for age 8 to 20 years (99 subjects) because breath-holds were more consistent in this group. When indexed for body surface area or height, the centile curves of ventricular volumetric parameters showed allometric increase until adolescence, when a plateau was reached, with values comparable to published adult reference data. In contrast, ventricular mass centiles increased without plateau. There was a significant sex difference, with centiles reflecting larger values in boys than in girls (P<0.05) when ventricular volumes were indexed to body surface area or height but not when indexed to weight (exception: mass). There was excellent agreement of axial and short-axis volumetry and of volumetric and flow-derived stroke volumes. Conclusions—Percentiles for ventricular volumes and mass in healthy children have been established to serve as reference values in pediatric heart disease. Significant sex differences were noted when indexing volumes to body surface area or height. Unisex centiles related to weight may be considered for chamber volumes albeit not for mass.


Circulation-cardiovascular Imaging | 2011

Assessment of Diffuse Myocardial Fibrosis in Rats Using Small-Animal Look-Locker Inversion Recovery T1 Mapping

Daniel Messroghli; Sarah Nordmeyer; Thore Dietrich; Olaf Dirsch; Elena Kaschina; Kostas Savvatis; Darach O h-Ici; Christoph Klein; Felix Berger; Titus Kuehne

Background— The concentration of gadopentetate dimeglumine in myocardium and blood can be assessed from T1 measurements and can be used to calculate the extracellular volume (ECV) of the myocardium. We hypothesized that diffuse myocardial fibrosis in a small-animal model could be quantitatively assessed by measuring myocardial ECV using small-animal Look-Locker inversion recovery T1 mapping. Methods and Results— Sprague-Dawley rats (n=10) were subjected to continuous angiotensin-2 (AT2) infusion for 2 weeks via a subcutaneously implanted minipump system. Magnetic resonance imaging (MRI) was performed both before and after AT2 infusion. The MRI protocol included multislice cine imaging and before-and-after contrast small-animal Look-Locker inversion recovery T1 mapping and late gadolinium enhancement imaging. Myocardial ECV was calculated from hematocrit and T1 values of blood and myocardium. During the course of AT2 infusion, the mean±SD systolic blood pressure increased from 122±10.9 to 152±27.5 mm Hg (P=0.003). Normalized heart weight was significantly higher in AT2-treated animals than in control littermates (P=0.033). Cine MRI documented concentric left ventricular hypertrophy. Postcontrast myocardial T1 times were shortened after treatment (median [interquartile range], 712 [63] versus 820 [131] ms; P=0.002). Myocardial ECV increased from 17.2% (4.3%) before to 23.0% (6.2%) after AT2 treatment (P=0.031), which was accompanied by perivascular fibrosis and microscarring on myocardial histological analysis. There was a moderate level of correlation between ECV and collagen volume fraction, as assessed by histological analysis (r=0.69, P=0.013). Conclusions— In a small-animal model of left ventricular hypertrophy, contrast-enhanced T1 mapping can be used to detect diffuse myocardial fibrosis by quantification of myocardial ECV.


Heart | 2005

Magnetic resonance imaging guided catheterisation for assessment of pulmonary vascular resistance: in vivo validation and clinical application in patients with pulmonary hypertension

Titus Kuehne; S Yilmaz; I Schulze-Neick; E Wellnhofer; P Ewert; Eike Nagel; Peter Lange

Objectives: To validate in vivo a magnetic resonance imaging (MRI) method for measurement of pulmonary vascular resistance (PVR) and subsequently to apply this technique to patients with pulmonary hypertension (PHT). Methods and results: PVR was assessed from velocity encoded cine MRI derived pulmonary artery (PA) flow volumes and simultaneously determined invasive PA pressures. For pressure measurements flow directed catheters were guided under magnetic resonance fluoroscopy at 1.5 T into the PA. In preliminary validation studies (eight swine) PVR was determined with the thermodilution technique and compared with PVR obtained by MRI (0.9 (0.5) v 1.1 (0.3) Wood units·m2, p  =  0.7). Bland-Altman test showed agreement between both methods. Inter-examination variability was high for thermodilution (6.2 (2.2)%) but low for MRI measurements (2.1 (0.3)%). After validation, the MRI method was applied in 10 patients with PHT and five controls. In patients with PHT PVR was measured at baseline and during inhalation of nitric oxide. Compared with the control group, PVR was significantly increased in the PHT group (1.2 (0.8) v 13.1 (5.6) Wood units·m2, p < 0.001) but decreased significantly to 10.3 (4.6) Wood units·m2 during inhalation of nitric oxide (p < 0.05). Inter-examination variability of MRI derived PVR measurements was 2.6 (0.6)%. In all experiments (in vivo and clinical) flow directed catheters were guided successfully into the PA under MRI control. Conclusions: Guidance of flow directed catheters into the PA is feasible under MRI control. PVR can be determined with high measurement precision with the proposed MRI technique, which is a promising tool to assess PVR in the clinical setting.


Journal of Magnetic Resonance Imaging | 2009

Cardiac function by MRI in congenital heart disease: Impact of consensus training on interinstitutional variance

Philipp Beerbaum; Peter Barth; Siegfried Kropf; Samir Sarikouch; Andrea Kelter-Kloepping; Diana Franke; Matthias Gutberlet; Titus Kuehne

To investigate the impact of interinstitutional variance (=interobserver variance between institutions) for volumetric and flow cardiac MR (CMR) data and if training on image reading could improve bias.


Journal of Magnetic Resonance Imaging | 2010

Flow‐sensitive four‐dimensional cine magnetic resonance imaging for offline blood flow quantification in multiple vessels: A validation study

Sarah Nordmeyer; Eugénie Riesenkampff; Gerard Crelier; Alireza Khasheei; Bernhard Schnackenburg; Felix Berger; Titus Kuehne

To further validate the quantitative use of flow‐sensitive four‐dimensional velocity encoded cine magnetic resonance imaging (4D VEC MRI) for simultaneously acquired venous and arterial blood flow in healthy volunteers and for abnormal flow in patients with congenital heart disease.


Circulation-cardiovascular Imaging | 2008

Functional analysis of the components of the right ventricle in the setting of tetralogy of Fallot.

Narendra Kuber Bodhey; Philipp Beerbaum; Samir Sarikouch; Siegfried Kropf; Peter Lange; Felix Berger; Robert H. Anderson; Titus Kuehne

Background—Anatomic and functional observations suggest that the right ventricle (RV) can be analyzed in terms of its inlet, apical trabecular, and outlet components. Our study was designed to evaluate the regional adaptation of these components to different conditions of loading, with additional analysis of the surgical techniques used for primary repair. Methods and Results—We studied prospectively 45 patients with tetralogy of Fallot (age, 20.5±8.1 years) and 24 control subjects (age, 20.1±5.8 years). All subjects were studied by using cardiac MRI. End-diastolic (EDV), end-systolic (ESV), stroke volumes (SV), and ejection fraction (EF) were determined for the overall RV and separately for its inlet, apical trabecular, and outlet components. The patients had pulmonary regurgitant fractions of 33.2±11.1%, and RV peak-systolic pressures of 40.7±16.1 mm Hg. In controls, the apical trabecular component EDV was 51.5±11.1 mL/m2 (54.3±6.8% of the total RV EDV), ESV was 19.2±6.3 mL/m2 (47.6±10.5% of RV ESV), and SV was 32.3±6.9 mL/m2 (58.9±6.6% of RV SV), resulting in an EF of 63.1±7.7%. When considering all patients, the apical trabecular component took up the greatest part of the overload, having an EDV of 76.5±18.1 mL/m2, and an ESV of 31.6±12.8 mL/m2, reflecting an increase of 49 and 67% over controls, respectively (P<0.001). EF was 59.7±10.7%, and was maintained at control levels (P=0.132). In controls, the outlet had considerable ejecting force, with an EF of 54.8±9.1%, whereas it was decreased in the patients with tetralogy (EF=28.5±11.9%). There was significant increase of ESV (P<0.001), but not of EDV, with EF decreased by 45% (P<0.001). The inlet was not significantly affected by overload. The surgical technique did not significantly affect any measured parameter for any component. Conclusions—In patients with tetralogy of Fallot, subsequent to surgical correction, the individual components of the RV respond in characteristic fashion to RV overload.


Journal of Cardiovascular Magnetic Resonance | 2012

Systemic-to-pulmonary collateral flow in patients with palliated univentricular heart physiology: measurement using cardiovascular magnetic resonance 4D velocity acquisition

Israel Valverde; Sarah Nordmeyer; Sergio Uribe; Gerald Greil; Felix Berger; Titus Kuehne; Philipp Beerbaum

BackgroundSystemic-to-pulmonary collateral flow (SPCF) may constitute a risk factor for increased morbidity and mortality in patients with single-ventricle physiology (SV). However, clinical research is limited by the complexity of multi-vessel two-dimensional (2D) cardiovascular magnetic resonance (CMR) flow measurements. We sought to validate four-dimensional (4D) velocity acquisition sequence for concise quantification of SPCF and flow distribution in patients with SV.Methods29 patients with SV physiology prospectively underwent CMR (1.5 T) (n = 14 bidirectional cavopulmonary connection [BCPC], age 2.9 ± 1.3 years; and n = 15 Fontan, 14.4 ± 5.9 years) and 20 healthy volunteers (age, 28.7 ± 13.1 years) served as controls. A single whole-heart 4D velocity acquisition and five 2D flow acquisitions were performed in the aorta, superior/inferior caval veins, right/left pulmonary arteries to serve as gold-standard. The five 2D velocity acquisition measurements were compared with 4D velocity acquisition for validation of individual vessel flow quantification and time efficiency. The SPCF was calculated by evaluating the disparity between systemic (aortic minus caval vein flows) and pulmonary flows (arterial and venour return). The pulmonary right to left and the systemic lower to upper body flow distribution were also calculated.ResultsThe comparison between 4D velocity and 2D flow acquisitions showed good Bland-Altman agreement for all individual vessels (mean bias, 0.05±0.24 l/min/m2), calculated SPCF (−0.02±0.18 l/min/m2) and significantly shorter 4D velocity acquisition-time (12:34 min/17:28 min,p < 0.01). 4D velocity acquisition in patients versus controls revealed (1) good agreement between systemic versus pulmonary estimator for SPFC; (2) significant SPCF in patients (BCPC 0.79±0.45 l/min/m2; Fontan 0.62±0.82 l/min/m2) and not in controls (0.01 + 0.16 l/min/m2), (3) inverse relation of right/left pulmonary artery perfusion and right/left SPCF (Pearson = −0.47,p = 0.01) and (4) upper to lower body flow distribution trend related to the weight (r = 0.742, p < 0.001) similar to the controls.Conclusions4D velocity acquisition is reliable, operator-independent and more time-efficient than 2D flow acquisition to quantify SPCF. There is considerable SPCF in BCPC and Fontan patients. SPCF was more pronounced towards the respective lung with less pulmonary arterial flow suggesting more collateral flow where less anterograde branch pulmonary artery perfusion.

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Shelby Kutty

University of Nebraska Medical Center

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