Publications by authors named "Nicolaj Lyhne Christensen"

15 Publications

  • Page 1 of 1

First-phase ejection fraction: association with remodelling and outcome in aortic valve stenosis.

Open Heart 2021 02;8(1)

Department of Cardiology, Odense University Hospital, Odense, Denmark.

Background: First-phase ejection fraction (EF1), the left ventricular (LV) ejection fraction (EF) until the time of peak transaortic velocity, is a novel marker of subclinical LV dysfunction able to predict adverse events in aortic stenosis (AS). This study investigated the association between end-systolic wall stress (ESWS) and EF1 in severe AS, as well as the prognostic value of EF1 in severe asymptomatic AS.

Methods: Two prospectively gathered cohorts of 94 asymptomatic patients and 108 symptomatic patients scheduled for aortic valve replacement (AVR), all with severe AS (aortic valve area <1 cm) were stratified according to the median value of EF1 (33%). EF1 was defined as the EF at peak transaortic velocity. Asymptomatic patients were followed up for 3 years for the combined end-point of death, AVR or admission with heart failure.

Results: EF1 correlated with EF and was inversely associated with ESWS. In multivariate regression analysis, ESWS (p<0.001) and replacement fibrosis measured by MRI (p=0.02) were associated with EF1. Among asymptomatic patients, EF1 above the median was associated with the combined primary endpoint (HR=0.53 (95% CI 0.33 to 0.87)), while global longitudinal strain and EF were not. Among 42 patients with discordant AS (mean gradient <40 mm Hg), EF1 above median was associated with the primary endpoint (HR 0.28 (95% CI 0.12 to 0.61)).

Conclusion: EF1 is an afterload-dependent measure that is associated with events in patients with asymptomatic severe AS. The afterload dependency of EF1 may be useful in timing of risk stratification in patients with discordant AS.

Trial Registration Numbers: NCT02395107 and NCT02316587.
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http://dx.doi.org/10.1136/openhrt-2020-001543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880107PMC
February 2021

The association between aortic valve calcification, cardiovascular risk factors, and cardiac size and function in a general population.

Int J Cardiovasc Imaging 2021 Feb 11;37(2):711-722. Epub 2020 Sep 11.

Department of Cardiology, Odense University Hospital, Sdr. Boulevard 29, 5500, Odense C, Denmark.

To determine the presence and extent of aortic valve calcification (AVC) quantified by non-contrast cardiac computed tomography (NCCT), to determine the association between traditional cardiovascular risk factors and AVC score, and to evaluate the association between AVC and cardiac size and function assessed by echocardiography, in a general population aged 65-75 years. A random sample of 2060 individuals were invited to undergo NCCT through which their AVC score was assessed. Individuals with an AVC score ≥ 300 arbitrary units (AU) were invited for a transthoracic echocardiography together with age-matched controls. Descriptive statistics and multiple regression analyses were performed to identify risk factors associated with AVC and to describe associations between AVC score and echocardiographic findings. Of 2060 individuals invited 664 males and 636 females participated. Among those, 455 (68.5%) of males and 358 (56.3%) of females had AVC scores > 0 AU. The median AVC score was 6 AU (IQR 0-3064). Seventy-seven (11.6%) males and 20 (3.1%) females had an AVC score ≥ 300 AU. In a multiple regression analysis, age, sex, prior cardiovascular disease, smoking, and hypertension were associated with AVC score, while diabetes, hypercholesterolemia and kidney function were not. Individuals with AVC ≥ 300 AU had higher peak and mean aortic valve gradient, smaller indexed aortic valve area, greater left ventricular mass, and larger left atrial (LA) volume. In a random population sample of individuals aged 65-75 years, AVC was common and associated with most known cardiovascular risk factors. AVC ≥ 300 AU was associated with concentric remodeling and LA dilatation.
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http://dx.doi.org/10.1007/s10554-020-02012-2DOI Listing
February 2021

Single massive thoracolithiasis.

BMJ Case Rep 2020 Aug 17;13(8). Epub 2020 Aug 17.

Department of Radiology, University Hospital of Odense, Odense C, Denmark

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http://dx.doi.org/10.1136/bcr-2020-237628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7437688PMC
August 2020

Sex differences in aortic valve calcification in severe aortic valve stenosis: association between computer tomography assessed calcification and valvular calcium concentrations.

Eur Heart J Cardiovasc Imaging 2021 04;22(5):581-588

Department of Cardiology, Odense University Hospital, J.B Winsløws Vej 4, DK-5000 Odense C, Denmark.

Aims: The aims of this study were to investigate the correlation and sex differences between total valve calcium, valve calcium concentration, and aortic valve calcification (AVC) in explanted valves from patients with severe aortic valve stenosis undergoing aortic valve replacement (AVR).

Methods And Results: Sixty-nine patients with severe aortic stenosis (AS) scheduled for elective AVR underwent echocardiography and cardiac computed tomography (CT) prior to surgery (AVCin vivo) and CT of the explanted aortic valve (AVCex vivo). Explanted valves were prepared in acid solution, sonicated, and analysed with Arsenazo III dye to estimate total valve calcium and valve calcium concentration. Median AVCex vivo was 2082 (1421-2973) AU; mean valve calcium concentration was 1.43 ± 0.42 µmol Ca2+/mg tissue; median total valve calcium 156 (111-255) mg Ca2+, and valve calcium density 52 (35-81) mg/cm2. AVC displayed a strong correlation with total valve calcium (R2 = 0.98, P < 0.001) and a moderate correlation with valve calcium concentration (R2 = 0.62, P < 0.001). Valvular calcium concentration was associated with sex, aortic valve area, and mean gradient. After adjusting for age and estimated glomerular filtration rate, sex and mean gradient remained associated with valve calcium concentrations.

Conclusion: AVC score provides a strong estimate for total valve calcium but to a lesser degree calcium concentration in the valve tissue of patients with severe AS. Females presented lower valvular calcium concentrations than males irrespective of AS severity, adding evidence and providing support to the important point that sex differences in valvular calcium concentration in AS does not reflect valvular size.
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http://dx.doi.org/10.1093/ehjci/jeaa096DOI Listing
April 2021

Lumbar artery aneurysm: A rare manifestation of vasculopathy in a patient with neurofibromatosis type 1.

Radiol Case Rep 2020 Mar 14;15(3):277-281. Epub 2020 Jan 14.

Department of Radiology, Sygehus Lillebaelt - Kolding Sygehus, Sygehusvej 24, 6000 Kolding, Denmark.

Lumbar artery aneurysms are rare but important to diagnose, since rupture can have serious consequences due to life-threatening hemorrhage. A 49-year-old male with Neurofibromatosis type 1 (NF-1) was admitted to the emergency room with abrupt onset of severe abdominal pain. Ultrasound examination was normal, noncontrast CT revealed a tapered retroperitoneal mass adjacent to the right psoas muscle. A multiphased contrast-enhanced CT scan raised suspicion of an arterial lumbar aneurysm and was confirmed by selective catheter based angiography. The patient underwent successful treatment with endovascular coiling and the patient was discharged within a few days after an uneventful course.
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http://dx.doi.org/10.1016/j.radcr.2019.12.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965510PMC
March 2020

Association between left ventricular diastolic function and right ventricular function and morphology in asymptomatic aortic stenosis.

PLoS One 2019 30;14(7):e0215364. Epub 2019 Jul 30.

Department of Cardiology Odense University Hospital, Odense, Denmark.

Background: Aortic stenosis (AS) is a progressive disease in which left ventricular (LV) diastolic dysfunction is common. However, the association between diastolic dysfunction and right ventricular (RV) loading conditions and function has not been investigated in asymptomatic AS patients.

Methods And Findings: A total of 41 patients underwent right heart catheterization and simultaneous echocardiography at rest and during maximal supine exercise, stratified according to resting diastolic function. Cardiac chamber size and morphology was assessed using cardiac magnetic resonance imaging (cMRI). RV stroke work index, pulmonary artery (PA) compliance, PA elastance, PA pulsatility index, and right atrial pressure (RAP) were calculated at rest and maximal exercise. Ten patients (24%) had normal LV filling pattern, 20 patients (49%) had grade 1, and 11 patients (27%) had grade 2 diastolic dysfunction. Compared to patients with normal diastolic filling pattern, patients with diastolic dysfunction had lower RV end-diastolic volume (66 ± 11 ml/m2 vs. 79 ± 15 ml/m2, p = 0.02) and end-systolic volume (25 ± 7 ml/m2 vs. 32 ± 9 ml/m2, p = 0.04). An increase in mean RAP to ≥15 mmHg following exercise was not seen in patients with normal LV filling, compared to 4 patients (20%) with mild and 7 patients (63%) with moderate diastolic dysfunction (p = 0.003). PA pressure and PA elastance was increased in grade 2 diastolic dysfunction and correlated with RV volume and maximal oxygen consumption (r = -0.71, p < 0.001).

Conclusions: Moderate diastolic dysfunction is associated with increased RV afterload (elastance), which is compensated at rest, but is associated with increased RAP and inversely related to maximal oxygen consumption during maximal exercise.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0215364PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667115PMC
February 2020

End-systolic wall stress in aortic stenosis: comparing symptomatic and asymptomatic patients.

Open Heart 2019;6(1):e001021. Epub 2019 Apr 9.

Cardiology, Odense University Hospital, Odense, Denmark.

Aims: In aortic stenosis (AS), there is poor association between symptoms and conventional markers of AS severity or left ventricular (LV) systolic function. This may reflect that symptoms arise from LV diastolic dysfunction or that aortic valve area (AVA) and transvalvular gradient do not reflect afterload. We aimed to study the impact of afterload (end-systolic wall stress [ESWS]) on the presence of symptoms in AS and to test whether symptoms are related to increased ESWS or LV remodelling.

Methods And Results: In a prospective study, ESWS was estimated by measuring LV wall thickness from MRI and estimated LV end systolic pressure from echocardiographic mean gradient and systolic blood pressure in 78 patients with severe AS scheduled for aortic valve replacement and 91 patients with asymptomatic severe AS. Symptomatic patients had lower indexed AVA (0.40±0.11 vs 0.45±0.09 cm/m, p=0.009). They had undergone more extensive remodelling (MRI LV mass index [LVMi]: 85±24 vs 69±17 g/m, p<0.0001), had higher tricuspid regurgitant gradient (24±8 mm Hg vs 19 ± 7 mm Hg, p=0.0001) and poorer global longitudinal strain (-15.6±3.8 vs -19.9±3.2%, p<0.0001). ESWS was higher among symptomatic patients (96±51 vs 76±25 kdynes/cm, p=0.003). Multivariate logistic regression identified echocardiographic relative wall thickness, tricuspid gradient, mitral deceleration time, early diastolic strain rate, MRI LVMi, MRI LV end-diastolic volume index and ESWS as independently associated with being symptomatic.

Conclusion: ESWS can be estimated from multimodality imaging combining MRI and echocardiography. It is correlated with LV remodelling and neurohormonal activation and is independently associated with symptomatic status in AS.
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http://dx.doi.org/10.1136/openhrt-2019-001021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519411PMC
April 2019

Relation of Left Atrial Size, Cardiac Morphology, and Clinical Outcome in Asymptomatic Aortic Stenosis.

Am J Cardiol 2017 Nov 16;120(10):1877-1883. Epub 2017 Aug 16.

Department of Cardiology, Odense University Hospital, 5000 C Odense, Denmark.

Left atrial (LA) dilation in asymptomatic severe aortic stenosis (AS) may be an indicator of advanced disease. We aimed to investigate the association between LA volume index and left ventricular (LV) morphology assessed with cardiac magnetic resonance imaging (cMRI), and to assess the association with cardiac events. Ninety-two asymptomatic patients with aortic valve area <1 cm, aortic peak jet velocity >3.5 m/s, and ejection fraction ≥50% were prospectively enrolled and divided according to echocardiographic-derived LA volume index  <35 ml/m. Patients underwent echocardiography, cMRI, exercise testing, and were followed for the composite end point of death, readmission, or aortic valve replacement. Aortic valve area index was similar (0.45 ± 0.08 cm/m vs 0.45 ± 0.09 cm/m, p = 0.85) in patients with a dilated and normal LA. On cMRI patients with dilated LA were characterized by higher LV mass index (73 ± 17 g/m vs 66 ± 16 g/m, p = 0.03), increased right ventricle (70 ± 14 ml/m vs 63 ± 12 ml/m, p = 0.01) and LV end-diastolic volume index (84 ± 18 ml/m vs 77 ± 16 ml/m, p = 0.05), and higher brain natriuretic peptide. Late enhancement pattern was similar. During follow-up 20 events were recorded in patients with LA dilation compared with 8 in patients with normal LA (adjusted hazard ratio 2.77, 95% confidence interval 1.19 to 6.46, p = 0.02); also B-type natriuretic peptide  >125 pg/ml was associated with adverse outcome (adjusted hazard ratio 3.63, 95% confidence interval interval 1.28 to 10.32, p = 0.02). LA dilation is associated with LV remodeling and provides prognostic information in severe asymptomatic AS.
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http://dx.doi.org/10.1016/j.amjcard.2017.07.101DOI Listing
November 2017

Association Between Left Atrial Dilatation and Invasive Hemodynamics at Rest and During Exercise in Asymptomatic Aortic Stenosis.

Circ Cardiovasc Imaging 2016 Oct;9(10)

From the Department of Cardiology, Odense University Hospital, Denmark (N.L.C., J.S.D., R.C.-S., R.B., E.V.S., L.V., J.E.M.); Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense (K.J.), and Department of Cardiology, Lillebaelt Hospital, Vejle, Denmark (F.H.S.).

Background: Transition from an asymptomatic to symptomatic state in severe aortic stenosis is often difficult to assess. Identification of a morphological sign of increased hemodynamic load may be important in asymptomatic aortic stenosis to identify patients at risk.

Methods And Results: Thirty-nine patients with asymptomatic severe aortic stenosis (aortic valve area <1 cm, peak jet velocity >3.5 m/s) underwent exercise testing with simultaneous invasive hemodynamic monitoring and Doppler echocardiography. Cardiac index, pulmonary artery pressure, and pulmonary capillary wedge pressure (PCWP) were recorded. Patients were followed up for the composite end point of death, unplanned hospitalization, or aortic valve replacement. Patients were stratified into 2 groups according to left atrial (LA) volume index ≥35 mL/m. In 25 patients (64%) LA volume index was ≥35 mL/m. Aortic valve area was similar between groups (0.81±0.15 versus 0.84±0.18 cm; P=0.58). PCWP was higher at rest and during exercise in patients with LA volume index ≥35 mL/m (P<0.01), despite similar cardiac index. At rest, PCWP was <12 mm Hg in 11 patients (44%) with LA dilatation, whereas PCWP was <25 mm Hg in 1 patient (4%) with exercise. LA volume index and E/e' predicted exercise PCWP>30 mm Hg with areas under the receiver operating curve of 0.75 and 0.84, respectively. During follow-up, 14 cardiac events were recorded. LA volume was associated with a hazard ratio of 1.90 (95% confidence interval, 0.92-4.15).

Conclusions: LA size reflects hemodynamic burden in patients with asymptomatic severe aortic stenosis. Quantitative measurements of LA and diastolic function are associated with left ventricular filling pressures with exercise and could be used to identify asymptomatic patients with increased hemodynamic burden.

Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02395107.
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http://dx.doi.org/10.1161/CIRCIMAGING.116.005156DOI Listing
October 2016

The Stop-Only-While-Shocking algorithm reduces hands-off time by 17% during cardiopulmonary resuscitation - a simulation study.

Eur J Emerg Med 2016 Dec;23(6):413-417

aDepartment of Gastroenterology and Hepatology, Vejle Hospital, a part of Lillebaelt Hospital, Vejle bDepartment of Pulmonary diseases, Bispebjerg Hospital, Copenhagen cCentre of Cancer Immunotherapy, Herlev Hospital, Herlev dDepartment of Emergency Medicine, Hospital of South-West Jutland, Esbjerg Departments of eEndocrinology fGastroenterology and Hepatology gCardiology hClinical Chemistry and Pharmacology iEmergency Medicine, Odense University Hospital jDepartment of Clinical Pharmacology, Institute of Public Health, University of Southern Denmark, Odense, Denmark.

Introduction: Reducing hands-off time during cardiopulmonary resuscitation (CPR) is believed to increase survival after cardiac arrests because of the sustaining of organ perfusion. The aim of our study was to investigate whether charging the defibrillator before rhythm analyses and shock delivery significantly reduced hands-off time compared with the European Resuscitation Council (ERC) 2010 CPR guideline algorithm in full-scale cardiac arrest scenarios.

Methods: The study was designed as a full-scale cardiac arrest simulation study including administration of drugs. Participants were randomized into using the Stop-Only-While-Shocking (SOWS) algorithm or the ERC2010 algorithm. In SOWS, chest compressions were only interrupted for a post-charging rhythm analysis and immediate shock delivery. A Resusci Anne HLR-D manikin and a LIFEPACK 20 defibrillator were used. The manikin recorded time and chest compressions.

Results: Sample size was calculated with an α of 0.05 and 80% power showed that we should test four scenarios with each algorithm. Twenty-nine physicians participated in 11 scenarios. Hands-off time was significantly reduced 17% using the SOWS algorithm compared with ERC2010 [22.1% (SD 2.3) hands-off time vs. 26.6% (SD 4.8); P<0.05].

Conclusion: In full-scale cardiac arrest simulations, a minor change consisting of charging the defibrillator before rhythm check reduces hands-off time by 17% compared with ERC2010 guidelines.
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http://dx.doi.org/10.1097/MEJ.0000000000000282DOI Listing
December 2016

Association between aortic valve calcification measured on non-contrast computed tomography and aortic valve stenosis in the general population.

J Cardiovasc Comput Tomogr 2016 Jul-Aug;10(4):309-15. Epub 2016 May 21.

Department of Cardiology, Odense University Hospital, Denmark; Cardiovascular Centre of Excellence (CAVAC), Denmark; Elitary Research Centre of Individualised Medicine in Arterial Disease (CIMA), Denmark. Electronic address:

Background: Aortic valve calcification (AVC) measured on non-contrast computed tomography (CT) has shown correlation to severity of aortic valve stenosis (AS) and mortality in patients with known AS. The aim of this study was to determine the association of CT verified AVC and subclinical AS in a general population undergoing CT.

Methods: CT scans from 566 randomly selected male participants (age 65-74) in the Danish cardiovascular screening study (DANCAVAS) were analyzed for AVC. All participants with a moderately or severely increased AVC score (≥300 arbitrary units (AU)) and a matched control group were invited for a supplementary echocardiography. AS was graded by indexed aortic valve area (AVAi) on echocardiography as moderate 0.6-0.85 cm(2)/m(2) and severe < 0.6 cm(2)/m(2), respectively. ROC- and regression analyses were performed.

Results: Due to prior valve surgery, and artifacts from ICD leads 16 individuals were excluded from the AVC scoring. Moderate or severe increased AVC was observed in 10.7% (95% CI: 8.4-13.7). Echocardiography was performed in 101 individuals; 32.7% (95% CI: 21.8 to 46.0) with moderate or high AVC score had moderate or severe AS, while none with no or low AVC. A ROC analysis defined an AVC score ≥588 AU to be suggestive of moderate or severe AS (AUC 0.89 ± 0.04, sensitivity 83% and specificity 87%). In the univariate analyses, AVC was the only variable significantly associated with AS.

Conclusions: This study indicates an association between CT verified AVC and subclinical AS.
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http://dx.doi.org/10.1016/j.jcct.2016.05.001DOI Listing
June 2017

Early Diastolic Strain Rate in Relation to Systolic and Diastolic Function and Prognosis in Aortic Stenosis.

JACC Cardiovasc Imaging 2016 05 13;9(5):519-28. Epub 2016 Apr 13.

Department of Cardiology, Odense University Hospital, Odense, Denmark.

Objectives: This study examined the impact of early mitral inflow velocity-to-early diastolic strain rate (E/SRe) ratio on long-term outcome after aortic valve replacement (AVR) in aortic stenosis (AS).

Background: In AS, increased filling pressures are associated with a poor prognosis and can be estimated using the early diastolic mitral inflow velocity-to-early diastolic velocity of the mitral annulus (E/e') ratio. Recent studies suggest that the E/SRe ratio surpasses the E/e' ratio in estimating outcome.

Methods: Pre-operative evaluation was performed in 121 patients with severe AS (aortic valve area <1 cm(2)) and left ventricular ejection fraction (LVEF) of >40% who were scheduled for AVR. Patients were divided according to E/SRe median and followed for 5 years. The primary endpoint was overall mortality.

Results: LVEF was lower (53 ± 7% vs. 56 ± 7%, respectively; p = 0.03) and a restrictive filling pattern more common (28% vs. 8%, respectively, p = 0.005) in patients with increased E/SRe ratio. Five-year overall mortality was increased in patients with high E/SRe (40% vs. 15%, respectively; p = 0.007). In univariate Cox regression analysis, E/SRe, age, European System for Cardiac Operative Risk Evaluation (EuroSCORE), LV mass index, left atrial volume index, LVEF, global longitudinal strain, E/e' ratio, and N-terminal pro-B-type natriuretic peptide level were univariate predictors of overall mortality, although when we adjusted for the predefined variables age, history of diabetes mellitus and LVEF, only E/SRe and left atrial volume index remained associated with overall mortality. Even when we included left atrial volume index in the multivariate model, E/SRe was significantly associated with overall mortality (hazard ratio [HR]: 2.2; 95% confidence interval [CI]: 1.1 to 4.4; p < 0.05); additionally, in a model with forward selection, E/SRe was the sole predictor (HR: 2.9; 95% CI: 1.6 to 5.5; p = 0.001. The overall log likelihood chi-square analysis of the predictive power of the multivariate model containing E/SRe was statistically superior to models based on the E/e' ratio.

Conclusions: Pre-operative E/SRe ratio was significantly associated with long-term post-operative survival and was superior to the E/e' ratio in patients with severe AS undergoing AVR. (Effect of Angiotensin II Receptor Blockers (ARB) on Left Ventricular Reverse Remodelling After Aortic Valve Replacement in Severe Valvular Aortic Stenosis; NCT00294775).
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http://dx.doi.org/10.1016/j.jcmg.2015.06.029DOI Listing
May 2016

Sudden cardiac death in asymptomatic aortic stenosis: is the valve to blame?

BMJ Case Rep 2016 Jan 7;2016. Epub 2016 Jan 7.

Department of Cardiology, University Hospital of Odense, Odense, Denmark.

An active 68-year-old man with asymptomatic severe aortic stenosis and normal functional capacity on a conventional bicycle exercise test underwent a haemodynamic stress test with simultaneous invasive haemodynamic monitoring and echocardiography during supine bicycle testing as part of a research project. With exercise, the patient developed pulmonary venous hypertension and mild regional wall motion abnormalities on echocardiography. The patient terminated the test due to exhaustion. In the recovery period, he developed sustained ventricular tachycardia and became unconscious. No symptoms were present during exercise or prior to cardiac arrest. The following coronary angiogram revealed significant 2-vessel disease, and the patient subsequently underwent successful aortic valve replacement and coronary-artery bypass graft surgery.
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http://dx.doi.org/10.1136/bcr-2015-211473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4716427PMC
January 2016
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