Oct 25, 2017

An overview of the latest publications


Read about the latest publications from center members below.

You can see the full overview here.

Posted by: Anonymous


Haugaa KH, Edvardsen T, Smiseth OA
Mechanical dyssynchrony-resurrected as a flashing and rocking parameter to predict prognosis after cardiac resynchronization therapy.
Eur Heart J Cardiovasc Imaging. 2017 Oct 1;18(10):1118-1119. doi: 10.1093/ehjci/jex198. No abstract available.
ISSN (Electronic): 2047-2412
PMID: 28984891

Clinicians want to implant those patients with cardiac resynchronization therapy (CRT) who can benefit from it in terms of quality of life, symptoms, and survival. Still, selection of these patients is not straight forward. We are continuously trying to improve the treatment by looking for new techniques, new parameters, new indices, to select the correct patients, to select the correct lead position and pacing site(s), to select the correct device programming and to select the correct response parameters. Among a myriad of response parameters to CRT, the reduction of end-systolic volume (ESV) is widely in use and has been used in several trials.

We need further prospective studies to explore if other echocardiographic parameters can assess response to CRT. Studies should investigate if parameters of mechanical dyssynchrony which are closely related to the electrical conduction delay, such as wasted myocardial work, septal flash and apical rocking may be used to identify CRT responders in line with the notion that markers of dyssynchrony are good predictors of CRT response if they reflect electrical conduction delay.

In summary, this study supports recent reports and the simple idea that correcting dyssynchrony is the main target for CRT. Mechanical dyssynchrony has failed as a selection parameter for CRT, but seems to be an excellent response parameter after CRT implantation to predict prognosis.



Ross S, Odland HH, Aranda A, Edvardsen T, Gammelsrud LO, Haland TF, Cornelussen R, Hopp E, Kongsgaard E
Cardiac resynchronization therapy when no lateral pacing option exists: vectorcardiographic guided non-lateral left ventricular lead placement predicts acute hemodynamic response.
Europace. 2017 Sep 23. doi: 10.1093/europace/eux249. [Epub ahead of print]
ISSN (Electronic): 1532-2092
PMID: 29036446

A difficult cardiac resynchronization therapy (CRT) implantation scenario emerges when no lateral pacing option exists. The aim of this study was to explore the effect of biventricular pacing (BIVP) on vectorcardiographic parameters in patients with a non-lateral left ventricular (LV) lead position. We hypothesized that perimeter and area reduction for both the QRS complex and T-wave would predict acute CRT response.

ΔQRS-area is correlated to LV ΔdP/dtmax and predicts acute CRT response in patients with a non-lateral LV lead position. Assessment of ΔQRS-area might be a useful tool for patient specific LV lead placement when no lateral pacing option exists.

What's new:

  • Insight into the relationship between induced electrical propagation and acute hemodynamic response to cardiac resynchronization therapy (CRT) in patients with a non-lateral left ventricular (LV) lead position.
  • Vectorcardiographic assessment of QRS area is a useful non-invasive tool for acute CRT response prediction in patients with no lateral pacing options.
  • With a non-lateral LV lead position, acute hemodynamic response to CRT can be observed despite a shorter LV electrical delay (Q-LV) than the recommended cut-off value.



Bruse JL, Zuluaga MA, Khushnood A, McLeod K, Ntsinjana HN, Hsia TY, Sermesant M, Pennec X, Taylor AM, Schievano S
Detecting Clinically Meaningful Shape Clusters in Medical Image Data: Metrics Analysis for Hierarchical Clustering Applied to Healthy and Pathological Aortic Arches.
IEEE Trans Biomed Eng. 2017 Oct;64(10):2373-2383
ISSN (Electronic): 1558-2531
PMID: 28221991

Today's growing medical image databases call for novel processing tools to structure the bulk of data and extract clinically relevant information. Unsupervised hierarchical clustering may reveal clusters within anatomical shape data of patient populations as required for modern precision medicine strategies. Few studies have applied hierarchical clustering techniques to three-dimensional patient shape data and results depend heavily on the chosen clustering distance metrics and linkage functions. In this study, we sought to assess clustering classification performance of various distance/linkage combinations and of different types of input data to obtain clinically meaningful shape clusters.

We present a processing pipeline combining automatic segmentation, statistical shape modeling, and agglomerative hierarchical clustering to automatically subdivide a set of 60 aortic arch anatomical models into healthy controls, two groups affected by congenital heart disease, and their respective subgroups as defined by clinical diagnosis. Results were compared with traditional morphometrics and principal component analysis of shape features.

Clustering results vary depending on the distance/linkage combination used to divide the data. Yet, clinically relevant shape clusters and subgroups could be found with high specificity and low misclassification rates.

Detecting disease-specific clusters within medical image data could improve image-based risk assessment, treatment planning, and medical device development in complex disease.



Dahlslett T, Karlsen S, Grenne B, Sjøli B, Bendz B, Skulstad H, Smiseth OA, Edvardsen T, Brunvand H
Intra-Aortic Balloon Pump Optimizes Myocardial Function During Cardiogenic Shock.
JACC Cardiovasc Imaging. 2017 Aug 11. pii: S1936-878X(17)30607-1
doi: 10.1016/j.jcmg.2017.05.019. [Epub ahead of print] No abstract available.
ISSN (Electronic): 1876-7591
PMID: 28823741

The intra-aortic balloon pump (IABP) has been the most widely used mechanical device for hemodynamic support in patients with cardiogenic shock complicating acute myocardial infarction (AMI) for more than 40 years. Recently, the use of IABP has been questioned due to limited evidence of clinical value. However, selected patients may benefit from IABP and improved methods for patient selection are warranted. The cardiomechanical effect of IABP on myocardial function and hemodynamics are mostly studied in experimental and animal models, but are lacking in humans with cardiogenic shock after AMI. Our aim was to investigate the cardiomechanical and hemodynamic effects of IABP as measured by echocardiographic strain on left ventricular (LV) function in patients with cardiogenic shock after AMI, in order to identify patients who may respond to IABP treatment.

To conclude, in patients with cardiogenic shock complicating AMI, IABP reduced LV volumes and improved global LV function by reducing passive myocardial stretch and by increasing circumferential contraction in nonischemic segments. These cardiomechanical responses to IABP can be monitored bedside by use of strain echocardiography and may be a useful method to verify positive cardiomechanical response to IABP with potential clinical benefit. The results are consistent with earlier studies from animal models and suggest a small, but favorable cardiomechanical response to treatment with IABP counterpulastion in selected patients with cardiogenic shock complicating AMI.



Dejgaard LA, Haland TF, Lie OH, Ribe M, Bjune T, Leren IS, Berge KE, Edvardsen T, Haugaa KH
Data on exercise and cardiac imaging in a patient cohort with hypertrophic cardiomyopathy.
Data Brief. 2017 Sep 12;15:30-39. doi: 10.1016/j.dib.2017.08.018. eCollection 2017 Dec.
ISSN (Print): 2352-3409
PMID: 28971120

Data presented in this paper are supplementary material to our study “Vigorous exercise in patients with hypertrophic cardiomyopathy”. The current article presents supplementary data on collection and analyses of exercise parameters and genetic data in the original research article.


Klaeboe LG, Haland TF, Leren IS, Ter Bekke RMA, Brekke PH, Røsjø H, Omland T, Gullestad L, Aakhus S, Haugaa KH, Edvardsen T
Prognostic Value of Left Ventricular Deformation Parameters in Patients with Severe Aortic Stenosis: A Pilot Study of the Usefulness of Strain Echocardiography.
J Am Soc Echocardiogr. 2017 Aug;30(8):727-735.e1.
ISSN (Electronic): 1097-6795
PMID: 28599826

Once symptoms occur, the annual risk for sudden death in previously truly asymptomatic patients with severe AS rises from approximately 1% to 3%, and if left untreated, symptomatic patients have poor outcomes, particularly those with heart failure symptoms or syncope.

The recommendations for aortic valve (AV) replacement (AVR) are strong when AS causes symptoms or myocardial impairment. However, patients can adapt to a sedentary state, thus avoiding symptoms and complicating clinical assessment. A symptomatic state largely reflects the failure of myocardial compensatory mechanisms, emphasizing that evaluation of the myocardial condition is important in decision making regarding AVR.

In patients with aortic stenosis, subtle alterations in myocardial mechanics can be detected by speckle-tracking echocardiography before reduction of left ventricular ejection fraction (LVEF).

Increased mechanical dispersion may be a risk marker providing novel prognostic information in patients with aortic stenosis.


Ruddox V, Sandven I, Munkhaugen J, Skattebu J, Edvardsen T, Otterstad JE
Atrial fibrillation and the risk for myocardial infarction, all-cause mortality and heart failure: A systematic review and meta-analysis.
Eur J Prev Cardiol. 2017 Sep;24(14):1555-1566
ISSN (Electronic): 2047-4881
PMID: 28617620

In contemporary atrial fibrillation trials most deaths are cardiac related, whereas stroke and bleeding represent only a small subset of deaths. We aimed to evaluate the long-term risk of cardiac events and all-cause mortality in individuals with atrial fibrillation compared to no atrial fibrillation.

A systematic review and meta-analysis of studies published between 1 January 2006 and 21 October 2016.

Four databases were searched. Studies had follow-up of at least 500 stable patients for either cardiac endpoints or all-cause mortality for 12 months or longer. Publication bias was evaluated and random effects models were used to synthesise the results. Heterogeneity between studies was examined by subgroup and meta-regression analyses.

A total of 15 cohort studies was included. Analyses indicated that atrial fibrillation was associated with an increased risk of myocardial infarction (relative risk (RR) 1.54, 95% confidence interval (CI) 1.26-1.85), all-cause mortality (RR 1.95, 95% CI 1.50-2.54) and heart failure (RR 4.62, 95% CI 3.13-6.83). Coronary heart disease at baseline was associated with a reduced risk of myocardial infarction and explained 57% of the heterogeneity. A prospective cohort design accounted for 25% of all-cause mortality heterogeneity. Due to there being fewer than 10 studies, sources of heterogeneity were inconclusive for heart failure.

Atrial fibrillation seems to be associated with an increased risk of subsequent myocardial infarction in patients without coronary heart disease and an increased risk of, all-cause mortality and heart failure in patients with and without coronary heart disease.


Stokke TM, Hasselberg NE, Smedsrud MK, Sarvari SI, Haugaa KH, Smiseth OA, Edvardsen T, Remme EW
Geometry as a Confounder When Assessing Ventricular Systolic Function: Comparison Between Ejection Fraction and Strain.
J Am Coll Cardiol. 2017 Aug 22;70(8):942-954
ISSN (Electronic): 1558-3597
PMID: 28818204

Preserved left ventricular (LV) ejection fraction (EF) and reduced myocardial strain are reported in patients with hypertrophic cardiomyopathy, ischemic heart disease, diabetes mellitus, and more.

The authors performed a combined mathematical and echocardiographic study to understand the inconsistencies between EF and strains.

Calculated EF had very good agreement with measured EF (r = 0.95). The model showed that GCS contributes more than twice as much to EF than GLS. A significant reduction of GLS could be compensated by a small increase of GCS or wall thickness or reduced diameter. The model further demonstrated how EF can be maintained in ventricles with increased wall thickness or reduced diameter, despite reductions in both longitudinal and circumferential shortening. This was consistent with similar EF in 20 control subjects and 20 hypertrophic cardiomyopathy patients with increased wall thickness and reductions in both circumferential and longitudinal shortening (all p < 0.01).

Reduced deformation despite preserved EF can be explained through geometric factors. Due to geometric confounders, strain better reflects systolic function in patients with preserved EF.


Timmermann V, Dejgaard LA, Haugaa KH, Edwards AG, Sundnes J, McCulloch AD, Wall ST
An integrative appraisal of mechano-electric feedback mechanisms in the heart.
Prog Biophys Mol Biol. 2017 Aug 26. pii: S0079-6107(17)30047-0
doi: 10.1016/j.pbiomolbio.2017.08.008. [Epub ahead of print]
ISSN (Electronic): 1873-1732
PMID: 28851517

Mechanically-induced alterations in cardiac electrophysiology are referred to as mechano-electric feedback (MEF), and play an important role in electrical regulation of cardiac performance. The influence of mechanical stress and strain on electrophysiology has been investigated at all levels, however the role of MEF in arrhythmia remains poorly understood. During the normal contraction of the heart, mechano-sensitive processes are an implicit component of cardiac activity. Under abnormal mechanical events, stretch-activated mechanisms may contribute to local or global changes in electrophysiology (EP). While such mechanisms have been hypothesised to be involved in mechanically-initiated arrhythmias, the details of these mechanisms and their importance remain elusive.

We assess the theoretical role of stretch mechanisms using coupled models of cellular electrophysiology and sarcomere contraction dynamics. Using models of single ventricular myocytes, we first investigated the potential MEF contributions of stretch-activated currents (SAC), and stretch-induced myofilament calcium release, to test how strain and fibrosis may alter cellular electrophysiology. For all models investigated, SACs were alone not sufficient to create a pro-arrhythmic perturbation of the action potential with stretch. However, when combined with stretch-induced myofilament calcium release, the action potential could be shortened depending on the timing of the strain. This effect was highly model dependent, with a canine epicardial EP model being the most sensitive.

These model results suggest that known mechanisms of mechano-electric coupling in cardiac myocyte may be sufficient to be pro-arrhythmic, but only in combination and under specific strain patterns.

Center for Cardiological Innovation