
==== Front
Interdiscip Cardiovasc Thorac Surg
Interdiscip Cardiovasc Thorac Surg
icvts
Interdisciplinary Cardiovascular and Thoracic Surgery
2753-670X
Oxford University Press

39254640
10.1093/icvts/ivae154
ivae154
Valvular Heart Disease
Residents’ Corner
Eacts/114
Eacts/106
Eacts/180
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AcademicSubjects/MED00920
Characterisation of global and regional mitral annular strains in an acute porcine model
https://orcid.org/0000-0002-7835-367X
Persson Robert Matongo Department of Heart Disease, Haukeland University Hospital, Bergen, Norway
Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway

https://orcid.org/0000-0002-1438-5082
Aguilera Hans Martin Dahl Department of Structural Engineering, Faculty of Engineering Science, The Norwegian University of Science and Technology, Trondheim, Norway

https://orcid.org/0000-0002-4778-9470
Grong Ketil Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway

https://orcid.org/0000-0001-5648-7688
Kvitting John-Peder Escobar Department of Cardiothoracic Surgery, Oslo University Hospital, Rikshospitalet, Oslo, Norway
Institute of Clinical Medicine, University of Oslo, Oslo, Norway

https://orcid.org/0000-0002-9283-9588
Stangeland Lodve Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway

https://orcid.org/0000-0002-3242-7602
Haaverstad Rune Department of Heart Disease, Haukeland University Hospital, Bergen, Norway
Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway

https://orcid.org/0000-0003-3775-8870
Urheim Stig Department of Heart Disease, Haukeland University Hospital, Bergen, Norway
Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway

https://orcid.org/0000-0002-8761-5088
Prot Victorien Emile Department of Structural Engineering, Faculty of Engineering Science, The Norwegian University of Science and Technology, Trondheim, Norway

Corresponding author. Department of Heart Disease, Haukeland University Hospital, Postboks 1400, 5021 Bergen, Norway. Tel: +47-451-809-30; e-mail: robert.matongo.persson@helse-bergen.no (R.M. Persson).
9 2024
10 9 2024
10 9 2024
39 3 ivae15422 5 2024
01 8 2024
06 9 2024
14 9 2024
© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

Abstract

OBJECTIVES

This study aimed to explore regional mitral annular strain using a novel computational method.

METHODS

Eight pigs underwent implantation with piezoelectric transducers around the mitral annulus. Interventions of pre- and afterload were performed by inferior vena cava constriction and endovascular balloon occlusion of the descending aorta. The mitral annulus was reconstructed in a mathematical model and divided into 6 segments. Global and segmental annular strain were calculated from a discrete mathematical representation.

RESULTS

Global annular strain gradually decreased after isovolumetric contraction until late systole. Mitral annular end-systolic strain demonstrated shortening in all segments except the anterior segment, which showed the least deformation. The P2 annular segment demonstrated the most end-systolic shortening (–7.6 ± 1.1% at baseline, P < 0.001 compared to anterior segment). Systolic global annular strain showed no significant change in response to load interventions but correlated positively with left ventricular contractility at baseline and after preload reduction.

CONCLUSIONS

Mitral annular systolic strain demonstrates cyclical variations with considerable regional heterogeneity, with the most pronounced deformation in posterior annular segments. Measurements appear independent of changes to pre- and afterload.

Strain measurements are routinely used to quantify the global and regional function of the left ventricle [1].

Graphical abstract

Mitral annular strain
Strain imaging
Mitral annular dynamics
Mitral valve annulus
Mitral valve physiology
Mitral regurgitation
Western Norway Regional Health Authority and Simon Fougner Hartmann’s Foundation
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pmcINTRODUCTION

Strain measurements are routinely used to quantify the global and regional function of the left ventricle [1]. However, strain measurements have not yet been applied to the dynamics of the human mitral annulus. The importance of annular dysfunction is becoming increasingly recognized in the disease progression of both degenerative and functional mitral regurgitation (MR) [2]. A more detailed understanding of the mitral annulus dynamic properties may clarify the pathophysiology of mitral valve disease, aid in timely diagnosis and guide treatment strategies [3, 4].

Previously, we have performed a detailed characterization of mitral annulus geometry through the cardiac cycle using an acute animal model [5]. Employing a novel method of in vivo mitral annular strain measurement, this study aimed to investigate regional variations of mitral annular strain and monitor acute effects from alterations in ventricular load and contractility.

MATERIALS AND METHODS

Ethical statement

The study protocol was approved by the Norwegian State Commission for Laboratory Animals (Project ID: 14687) and performed in compliance with the European Communities Council Directive of 2010 (63/EU).

Surgical preparations and acquisition of data

A detailed description of the experimental protocol has been published previously [5]. The study included 8 pigs (59, SD 5 kg) of either sex. The animals were sedated by intramuscular injection of ketamine (20 mg/kg), diazepam (10 mg) and atropine (1 mg) and mask-ventilated with 3% isoflurane. Anaesthesia was induced by intravenous administration of fentanyl (0.02 mg/kg), midazolam (0.3 mg/kg), pentobarbital (15 mg/kg) and pancuronium (0.063 mg/kg), and maintained by continuous infusion of fentanyl (0.02 mg/kg/h), midazolam (0.3 mg/kg/h), pancuronium (0.2 mg/kg/h) and pentobarbital (4 mg/kg/h). The animals were ventilated through a tracheotomy with a mixture of nitrous oxide (57–58%) and oxygen.

After exposure of the heart by median sternotomy and partial heparinization (125 IU/kg), micromanometer-tipped pressure transducers (MPC-500, Miller Instruments Inc., Houston, TX) were implanted transapically into the left ventricle and into the left atrium through the left atrial appendage. To allow accurate left ventricular (LV) volume estimation, four 2-mm piezoelectric transducers (Sonometrics Corp., London, ON, Canada) were sutured to the equator of the LV and one at the apex. Cardiopulmonary bypass was established after full heparinization, and the mitral valve was exposed in cardioplegic arrest.

Eight piezoelectric transducers were placed equidistantly around the mitral annulus and connected to a transceiver and acquisition system. Transducer positions were tracked at 117 Hz sampling frequency after ventilation was suspended in the end-expirium. Registrations were acquired after weaning from cardiopulmonary bypass at a stable baseline condition, after transient inferior cava constriction (ICC) by a surgical snare, and after occlusion of the descending aorta (AO) by inflation of an endovascular balloon through the femoral artery.

Data analysis

Measurements were acquired from baseline at a 20% decrease of LV end-diastolic pressure after ICC and at the plateau of LV pressure after AO. End-diastole was defined as the time step at which there was a rise in the 1st derivative of LV pressure (dP/dt), and end-systole at the time step of minimum LV volume. Haemodynamic data were processed as the mean of 3 consecutive heartbeats. All analyses were made with the heart in sinus rhythm and absence of MR.

LV volume was estimated from epicardial transducer positions by calculation of a two-axis ellipsoid model [6]. Transducer distances were corrected for apical, end-diastolic and end-systolic wall thickness obtained from echocardiography (EchoPAC version 112; GE Ultrasound, Horten, Norway). Volume and area measurements were indexed to body surface area [7]. End-systolic elastance (Ees) was used as an index of LV contractility and was calculated as the slope of a linear regression through the end-systolic pressure–volume of 10 sequential heartbeats during ICC.

For each time step, coordinates of annular transducers were calculated in a Cartesian format, and the mitral annulus was reconstructed by parametric natural cubic spline interpolation through the sequence of annular positions (MATLAB version 2023b; The MathWorks, Natick, MA) [8]. The annulus was discretized using parametrization, and Green-Lagrange strain was calculated from the reconstructed annular spline as described by Rausch et al. [9], representing the local length change between tangent points of the mitral annulus from the reference time frame (defined as end-diastole in this study) to any other time frame. Principal component analysis was used on the annular spline to define the anterior saddle horn of the mitral annulus [5]. Using this as a reference point, the annulus was divided into 6 equal segments by a length equation (3 anterior and 3 posterior) and labelled anterolateral, anterior (ANT), posteromedial and corresponding to each posterior scallop (P1–P3 annular segments) (Fig. 1), after which strain was computed for each segment. Datasets were normalized for time with linear temporal interpolation between raw data points. The mitral annular area was estimated by projecting the annular spline onto its corresponding least squares plane and calculating the two-dimensional area. Global annular strain (GAS) was calculated as a mean strain across all segments, and global annular strain rate as the temporal derivative of GAS. Negative strain is referred to as shortening and positive strain as lengthening, whereas changes in strain are termed deformation. Total systolic deformation (–Δsys) was calculated as the absolute difference between the maximum and minimum strain during ventricular systole.

Figure 1: Schematic of a reconstructed annular spline from the surgeon’s view. The anterior saddle horn (ASH) is defined, and the spline is divided into 3 equal anterior and posterior annular segments labelled anterolateral (AL), anterior (ANT), posteromedial (PM) and P1–P3 according to the corresponding scallop.

Data were analysed using GraphPad Prism version 9.4 (GraphPad Software, Boston, MA). Normality was tested using the Shapiro–Wilk test, after which One-way Analysis of Variance or Friedman Repeated Measures was used whenever appropriate. Post hoc multiple comparisons with Holm-Šídák’s or Dunn’s test were used to compare means of baseline with ICC and AO. Two-way RM-ANOVA with Holm-Šídák’s post hoc multiple contrasts analysed segmental strain, strain rate and deformation using load and annular segments as repeated/dependent factors. For correlations, simple linear regression with a 95% confidence interval was used and slopes were compared using a method equivalent to an Analysis of Covariance. Unless specified otherwise, values are provided as mean ± standard error or median (1st quartile; 3rd quartile). P-values were considered significant when <0.05.

RESULTS

Haemodynamic responses to load interventions

Table 1 shows LV haemodynamic responses to load interventions. In general, both end-diastolic, peak systolic and end-systolic LV pressures and volumes decreased during ICC (reduced preload) and increased during AO (increased afterload) compared to baseline.

Table 1: Left ventricular variables at baseline, transient inferior caval constriction (ICC) and aortic occlusion (AO)

Variable	Baseline	ICC	AO	RM-ANOVA	
HR (beats/min)	126 ± 9	125 ± 9	117 ± 9	P = 0.068	
LV-EDP (mmHg)	9.4 ± 0.7	7.5 ± 0.5a	13.3 ± 1.4a	P = 0.003	
LV-SPmax (mmHg)	72 ± 6	59 ± 7a	107 ± 6a	P < 0.001	
LV-ESP (mmHg)	62 ± 6	48 ± 7a	100 ± 6a	P < 0.001	
dP/dtmax (mmHg/s)	880 (710; 1307)	675 (528; 1235)	1188 (804; 1571)	P < 0.001	
LV-EDVi (ml/m2)	112 ± 8	100 ± 7a	119 ± 8a	P < 0.001	
LV-ESVi (ml/m2)	71 ± 5	68 ± 5a	79 ± 6a	P < 0.001	
LV-EF (%)	37 ± 1	32 ± 2a	34 ± 1a	P = 0.001	
E es (mmHg/ml)	2.42 ± 0.28			n.a.	
Values are mean ± SE or median (1st quartile; 3rd quartile), n = 8.

a Significantly different from baseline with multiple contrast tests.

dP/dtmax: maximum of the 1st derivative of left ventricular pressure; EDP: end-diastolic pressure; EDVi: end-diastolic volume indexed for body surface area; ESVi: end-systolic volume indexed for body surface area; Ees: slope of end-systolic pressure–volume relationship; EF: ejection fraction; ESP: end-systolic pressure; HR: heart rate; LV: left ventricle; n.a.: not applicable; SPmax: peak systolic pressure; RM-ANOVA: one-way repeated measurement ANOVA or Friedman Repeated Measures Analysis of Variance on Ranks.

Global and segmental annular strain

Cyclical variations of global and segmental annular strain and strain rate during baseline, ICC and AO normalized for time are shown in Fig. 2. GAS increased slightly during isovolumetric contraction and thereafter decreased until late systole. Except for the ANT segment, where only minor deformational changes were observed, all segments demonstrated shortening through systole after isovolumetric contraction with peak negative strain in late systole. Compared to baseline, mitral annular area indexed for body surface area decreased with preload reduction in both early systole (dP/dtmax) and end-systole (P = 0.0011 and P = 0.049), and increased with afterload increase at dP/dtmax (P = 0.0045) (Table 2). However, end-systolic GAS and global annular strain rate were not influenced by changes to pre- and afterload.

Figure 2: Mean and segmental annular strain and strain rate for baseline, transient inferior caval constriction (ICC) and aortic occlusion (AO) with corresponding mitral annular area indexed for body surface area (MAAi, blue) and the 1st derivative of left ventricular pressure (dP/dt, red), n = 8. AL: anterolateral segment; ANT: anterior segment; dP/dtmax: delineators for maximum dP/dt; ED: end-diastole; ES: end-systole; GAS: global annular strain; GASr: global annular strain rate; P1–P3 = posterior annular segments; PM: posteromedial segment.

Table 2: Mitral annular area, strain and strain rate at baseline, transient inferior caval constriction (ICC) and aortic occlusion (AO)

Variable	Baseline	ICC	AO	RM-ANOVA	
MAAi-dP/dtmax (mm2/m2)	629 ± 39	599 ± 40a	664 ± 39a	P < 0.001	
GAS-dP/dtmax (%)	1.1 ± 0.8	2.2 ± 1.0	0.6 ± 0.6	P = 0.026	
GASr-dP/dtmax (1/s)	43 (–26; 112)	10 (–42; 85)	14 (–14; 69)	P = 0.97	
MAAi-ES (mm2/m2)	552 ± 34	521 ± 33a	632 ± 46	P < 0.001	
GAS-ES (%)	–3.8 ± 0.8	–3.1 ± 0.9	–3.7 ± 0.6	P = 0.78	
GASr-ES (1/s)	17 ± 10	11 ± 8	16 ± 9	P = 0.68	
GAS-Δsys (%)	6.3 ± 0.8	6.6 ± 0.8	5.4 ± 0.7	P = 0.13	
Values are mean ± SE or median (1st quartile; 3rd quartile), n = 8. 

a Significantly different from baseline with multiple contrast tests.

–Δsys: total systolic deformation; –dP/dtmax and –ES: delineators for maximum of the 1st derivative of left ventricular pressure and end-systole; GAS: global annular strain; GASr: global annular strain rate; MAAi: mitral annular area indexed for body surface area; RM-ANOVA: one-way repeated measurement ANOVA or Friedman Repeated Measures Analysis of Variance on Ranks.

In early systole (dP/dtmax), the P3 segment demonstrated pronounced lengthening (5.0 ± 2.0%), with only minor deformational changes in the remaining segments at baseline and with preload reduction (Table 3). At end-systole, the strain was negative in all segments except for ANT. End-systolic shortening was most prominent in the posterior segments (P1–P3) and unaffected by loading conditions. Total segmental systolic deformation was highest in the P2 and P3 segments, independent of changes to load (Table 4). This differed significantly from the ANT segment, which showed the least total systolic deformation irrespective of loading condition.

Table 3: Mitral annular segmental strain at baseline, transient inferior caval constriction (ICC) and aortic occlusion (AO)

Variable	Baseline (a)	ICC (b)	AO (c)	Two-way RM-ANOVA	
dP/dtmax	
 AS-AL (%)	0.8 ± 0.8P3	0.2 ± 1.0P3	–1.2 ± 1.0P3	P load = 0.026

P segment < 0.001

P load × segment < 0.040

	
 AS-ANT (%)	1.5 ± 0.8	3.3 ± 1.3a,c	0.3 ± 0.7	
 AS-PM (%)	1.3 ± 1.8	1.4 ± 1.8P3	1.5 ± 1.5	
 AS-P1 (%)	–0.3 ± 0.7P3	1.1 ± 1.0P3	–0.5 ± 0.7P3	
 AS-P2 (%)	–0.2 ± 0.5P3	0.4 ± 0.8P3	–0.3 ± 0.7	
 AS-P3 (%)	5.0 ± 2.0	6.8 ± 2.1a,c	3.8 ± 1.8	
End-systole					
 AS-AL (%)	–3.0 ± 1.1	–2.8 ± 1.1	–3.4 ± 1.1	P load = 0.45

P segment < 0.002

P load × segment < 0.005

	
 AS-ANT (%)	0.5 ± 0.8	1.6 ± 1.1	–1.0 ± 0.6b	
 AS-PM (%)	–3.6 ± 2.4	–3.6 ± 2.2ANT	–2.4 ± 1.6	
 AS-P1 (%)	–4.7 ± 1.1ANT	–3.3 ± 1.4ANT	–5.0 ± 0.7	
 AS-P2 (%)	–7.6 ± 1.1ANT	–7.1 ± 1.2ANT	–6.9 ± 1.0ANT	
 AS-P3 (%)	–4.6 ± 1.2ANT	–3.6 ± 1.2ANT	–3.7 ± 1.2	
Values are mean ± SE, n = 8.

a,b,c Significant difference in the corresponding segment in column with corresponding lowercase letter.

ANT, P3 Significant difference from value(s) within corresponding intervention (load).

AL: anterolateral segment; ANT: anterior segment; AS: annular strain; dP/dtmax: maximum of the 1st derivative of left ventricular pressure; P1–P3 = posterior annular segments; PM: posteromedial segment; Two-way RM-ANOVA: two-way analysis of variance for repeated/related measurements; Pload, Psegment and Pload × segment: P-values for load intervention, annular segment and interaction between load and segment.

Table 4: Total systolic deformation of segmental annular strain (%) at baseline, transient inferior caval constriction (ICC) and aortic occlusion (AO)

Variable	Baseline (a)	ICC (b)	AO (c)	Two-way RM-ANOVA	
AS-Δsys AL (%)	4.7 ± 0.7PM,P2,P3	5.0 ± 0.7P2,P3	4.9 ± 0.8	P load = 0.013

P segment < 0.001

P load × segment < 0.001

	
AS-Δsys ANT (%)	3.4 ± 0.6	4.7 ± 1.1PM	2.4 ± 0.5b	
AS-Δsys PM (%)	8.5 ± 1.3ANT	8.2 ± 1.4	5.2 ± 1.1a,b	
AS-Δsys P1 (%)	6.4 ± 0.8P3	6.7 ± 0.8P3	5.9 ± 0.8	
AS-Δsys P2 (%)	9.3 ± 1.1ANT	9.7 ± 1.3AL,ANT	7.8 ± 1.4ANT,b	
AS-Δsys P3 (%)	10.7 ± 1.6ANT	11.7 ± 1.3ANT,P1	7.8 ± 1.5ANT,a,b	
Values are mean ± SE, n = 8.

a,b Significant difference in the corresponding segment in columns with corresponding lowercase letters.

AL,ANT,PM,P1,P2,P3 Significant difference from value(s) within the corresponding intervention (load).

AL: anterolateral segment; ANT: anterior segment; AS-Δsys: total systolic deformation of segmental annular strain; P1–P3: posterior annular segments; PM: posteromedial segment; Two-way RM-ANOVA: two-way analysis of variance for repeated/related measurements; Pload, Psegment and Pload × segment: P-values for load intervention, annular segment and interaction between load and segment.

Influence of ventricular contractility on annular strain

Dot plots with simple linear regression comparing the LV contractile index (Ees) and maximum systolic deformation of GAS (GAS-Δsys) can be viewed in Fig. 3. Ees was positively correlated to GAS-Δsys at baseline and ICC (r2 = 0.810; P = 0.0023 and r2 = 0.599; P = 0.024). There was no significant difference between slopes at baseline, ICC and AO (P = 0.47).

Figure 3: Linear regression with 95% confidence interval demonstrating the relationship between left ventricular contractile index (Ees) and total systolic deformation of global annular strain (GAS-Δsys) for baseline, transient inferior caval constriction (ICC) and aortic occlusion (AO), n = 8.

DISCUSSION

Principal findings

This study describes an in vivo method of measuring mitral annular strain and characterizes its cyclical variations. Most notably, the mitral annulus demonstrates significant heterogeneity in segmental deformation throughout the cardiac cycle. The most substantial shortening was observed in the P2 annular segment in late systole, and the ANT segment showed the most attenuated response in deformation through the cardiac cycle. Furthermore, GAS appears independent of changes to load, but dependent on LV contractility—where increased contractility was associated with accentuation of systolic deformation.

Anatomical correlate to strain variations

As the mitral annulus does not possess any inherent contractile elements, its dynamic motion is thought to result from atrial and ventricular contraction. Based on anatomical studies, the primary source of annular deformation in the systole is believed to be oblique muscle fibres that attach to the inlet of the left ventricle [10]. It can be argued that ventricular contraction is the most important mediator of mitral annulus deformation. Therefore, it is reasonable to assume that increased ventricular contractility accentuates the magnitude of annular deformation, as demonstrated in this study.

Regional anatomic features likely explain the heterogeneity of segmental annular deformation. The anterior part of the mitral annulus is in fibrous continuity with the aortic valve fibrous body [11]. On either side of the aortomitral continuity sit fibrous reinforcements that create the right and left trigones. The attenuated annular deformation of the ANT segment, which comprises most of the intertrigonal distance, is acknowledged to be a consequence of increased fibrous support. The reduced dynamics of the fibrous continuity have been described in experimental settings studying aortic–mitral annular relationship [12]. Although there are some disparities in the extension of the trigones, anatomical heterogeneity is especially evident in the posterior mitral annulus where histological studies have shown that the atrioventricular groove is interspersed with fibro-fatty tissue [13]. This causes reduced fibrous support, which likely explains the increased deformational properties demonstrated in the posterior annular segments.

A contributing factor may be the annular saddle shape, which is an essential mediator of stress distribution of the mitral valve apparatus. In one in vitro study using porcine mitral valves, flattening of the mitral annular saddle shape resulted in significantly increased strains on the P2 leaflet [14]. Although mitral annular strain was not studied, the relationship was evident in basal circumferential directions in proximity and parallel to the mitral annulus.

Comparison to previous works

The findings presented here are in general agreement with previous studies. Gunning and Murphy [15] performed tensile testing on porcine mitral samples and found increased stiffness in the anterior annulus compared to the posterior. The reduced extensibility of the anterior annulus was attributed to its collagen-dense extra-cellular matrix, where the load-bearing capability of the myocardium proved negligible. Interestingly, biomechanical failure was most pronounced in the P3 area, corresponding to the segment that demonstrated the most lengthening herein.

In vivo mitral annular strain has previously been described by Eckert et al. [16] and Rausch et al. [9] in ovine models based on the displacements of implanted fiducial markers. Similar to our results, both studies observed peak shortening of the posterior annulus in the middle or late systole. Eckert et al. also noted substantial regional variations in strain at given time points and more moderate changes in strain of the anterior annulus. Contrary to our findings, Rausch et al. reported peak lengthening in the anterior annulus. This inconsistency is possibly explained by inter-species differences in the fibrous support of the intertrigonal annulus. In previous animal experiments, both Tibayan et al. [17] and Parish et al. [18] found equally prominent annular dilatation in the anterior and posterior portion of the ovine annulus in response to ischaemic and load interventions. The reduced deformational properties of the ANT segment are likely even more marked in humans, where the extent of the aorto–mitral fibrous continuity is more pronounced than in the porcine heart [19].

Clinical inferences

It has been consistently demonstrated that mitral annular geometry and dynamics are altered in the setting of MR [3, 10, 20–22]. This is most evident in degenerative myxomatous disease (DMD), which commonly involves annular dilatation and disjunction in addition to leaflet redundancy and thickening [20]. Contrary to DMD, fibroelastic deficiency is frequently characterized by single-segment prolapse. Differentiating between these degenerative mitral valve disease phenotypes can prove challenging, and annular parameters can provide a discriminating feature [20].

Although the most distinctive attributes of DMD are valvular, the importance of annular dysfunction to the development of DMD is becoming increasingly recognized [3]. The prominent deformation of the posterior segments may also explain the distribution of disease observed in both fibroelastic deficiency and mitral annular disjunction. Failure to accommodate annular shortening during ventricular systole may increase leaflet stress and possibly precipitate chordal rupture, which most commonly occurs in the P2 area. Similarly, systolic outward motion and annular dilatation in mitral annular disjunction and DMD are most prevalent in the posterior–posteromedial annular area, where the highest systolic deformation was seen in this study. Annular dilatation is also implicated as a principal mechanism in developing functional MR in the absence of ventricular enlargement, frequently observed in patients with long-standing atrial fibrillation [21]. Conversely, only a subset of patients with atrial fibrillation are at risk of valvular incompetence [22]. Evaluating mitral annular strain may prove helpful to better understand the risk factors of both functional and degenerative MR.

While the geometry and dynamic motion of the mitral annulus have been thoroughly described [2], human mitral annular strain has not. This is likely due to the difficulty in tracking reference points from ultrasound images and the lack of a reproducible framework for annular strain measurements. We have previously provided a detailed description of annular dynamics and demonstrated that conventional variables of mitral annular geometry, such as mitral annulus area, saddle shape and circularity, are dependent on LV load and contractility [5]. In comparison, global mitral annular strain and strain rate appear more independent of load, making it more suitable for clinical application. Measurements of mitral annular strain can be applied to echocardiographic, computed tomography or magnetic resonance imaging data, either after manual or automatic segmentation, and may help distinguish phenotypes of mitral valve disease, identify treatment targets, and serve as an index of valvular stress in the functional assessments of patients.

A similar pipeline has been described for estimating mitral leaflet strains and applied to echocardiographic images of patients treated with transcatheter edge-to-edge repair for MR [23]. Mitral annular strain may also be useful in the evaluation and follow-up of patients treated with surgical or interventional therapies. Annuloplasty ring dehiscence has been demonstrated to be most frequently localized in the posterior annular segments, which has been attributed to lower collagen density and reduced suture-holding strengths [24]. However, the increased deformation of the posterior annular segments and corresponding association to LV contractility as described in this study may be contributing factors. A detailed characterization of mitral annular strains is also essential in developing reliable simulation models [4].

Study limitations

Several important limitations should be considered when interpreting the results of this study. First, the segmentation of the annular spline was not based on the anatomy of each specimen but on a length equation for improved reproducibility. Therefore, it should be noted that the annular segment does not correspond precisely to each valvular scallop. Second, it can be argued that the strain analysis is performed on a mathematical reconstruction of the mitral annulus instead of direct measurements from the piezoelectric transducers. Spline reconstruction is superior because it provides a more suitable representation of the complete mitral annulus anatomy and allows computational analysis irrespective of marker positions. Third, the study was performed as an open-chest experiment model in a small number of animals under general anaesthesia. This will influence both haemodynamic and general physiological functions. Also, the anatomy and characteristics of the porcine mitral annulus may differ from those of humans. For this reason, the extrapolation to human pathophysiology should be made with caution. Finally, the experimental design did not allow us to control variations in the LV contractile index resulting from the combined impact of anaesthetic agents and the surgical procedure with cardiopulmonary bypass.

CONCLUSION

This study demonstrates global and regional variations of mitral annular strain through the cardiac cycle. Deformation was most pronounced in the posterior segments of the mitral annulus, whereas only minimal deformation was observed in the ANT segment. With increased focus on annular dysfunction in mitral valve disease, mitral annular strain has the potential to act as an index of annular deformation that may prove valuable in several conceivable clinical situations.

ACKNOWLEDGEMENTS

The authors would like to acknowledge Pirjo-Riitta Salminen, Bård Svenheim, Anita Leiknes, Kjersti Milde and Cato Johnsen for their technical assistance at the animal research facility at the University of Bergen.

FUNDING

The work was supported by the Western Norway Regional Health Authority and Simon Fougner Hartmann’s Foundation.

Conflict of interest: none declared.

DATA AVAILABILITY

The data underlying the findings of this article will be made available upon reasonable request to the corresponding author.

Author contributions

Robert Matongo Persson: Conceptualization; Data curation; Formal analysis; Investigation; Methodology; Project administration; Resources; Software; Visualization; Writing—original draft; Writing—review & editing. Hans Martin Dahl Aguilera: Conceptualization; Data curation; Formal analysis; Methodology; Resources; Software; Writing—review & editing. Ketil Grong: Conceptualization; Data curation; Formal analysis; Methodology; Project administration; Supervision; Validation; Writing—review & editing. John-Peder Escobar Kvitting: Conceptualization; Data curation; Formal analysis; Investigation; Methodology; Supervision; Writing—review & editing. Lodve Stangeland: Conceptualization; Data curation. Rune Haaverstad: Conceptualization; Funding acquisition; Project administration; Supervision; Writing—review & editing. Stig Urheim: Conceptualization; Data curation; Formal analysis; Funding acquisition; Investigation; Methodology; Project administration; Resources; Supervision; Validation; Writing—review & editing. Victorien Emile Prot: Conceptualization; Formal analysis; Investigation; Methodology; Resources; Software; Validation; Visualization; Writing—original draft; Writing—review & editing.

Reviewer information

Interactive CardioVascular and Thoracic Surgery thanks Leo Pölzl, Thierry Bove and the other anonymous reviewers for their contribution to the peer review process of this article.

ABBREVIATIONS

–Δsys Total systolic deformation

ANT Anterior

AO Aortic occlusion

dP/dt First derivative of left ventricular pressure

dP/dtmax Maximum of the 1st derivative of left ventricular pressure

E es End-systolic elastance

GAS Global annular strain

ICC Inferior cava constriction

LV Left ventricular

MR Mitral regurgitation
==== Refs
REFERENCES

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