Mitral Regurgitation after Antero-Apical Myocardial Infarction: New Mechanistic Insights

Abstract

Background

Mitral regurgitation (MR) generally accompanies infero-basal myocardial infarction (MI), with leaflet tethering by displaced papillary muscles (PMs). MR is also reported with antero-apical MI without global dilatation or inferior wall-motion abnormalities. We hypothesized that anteroapical MI extending to the inferior apex displaces the PMs, tethering the mitral leaflets to cause MR.

Methods and Results

1. Retrospective study: Consecutive anteroapical MI patients were studied. Moderate-severe MR occurred in 9% of 234 pts with only anteroapical MI versus 17% of 242 with inferoapical extension (p<0.001). EF was only mildly different (41±4% vs 46±5%, p<0.01).

2. Human mechanistic study: Sixty anteroapical MI patients (20 with only two apical segments involved and 40 with involvement of all 4 apical segments, 20 with MR and 20 without MR), were compared to 20 normal controls. Those with MR (moderate) had higher systolic PM-to-annulus tethering length (TL) (p<0.01). MR grade correlated most strongly with TL (r=0.70) and its diminished systolic shortening (r=−0.65).

3. Animal study: 9 sheep with LAD ligation were analyzed. Four sheep that developed MR had inferoapical MI extension with TL increasing over 1.5 months (2.1±0.4 to 2.9±0.4 cm, p<0.001), versus no significant increase in 5 sheep without MR (2.0±0.4 to 2.1±0.3 cm, p=NS). In MR sheep, the normal decrease in TL from diastole to systole was eliminated (p<0.01).

Conclusions

Anteroapical MI with inferoapical extension can mechanically displace PMs, causing MR despite the absence of basal and mid-inferior wall motion abnormalities. This suggests the possibility of repositioning treatments for this condition.

Introduction

Ischemic mitral regurgitation (IMR) is a common complication of myocardial infarction (MI)^1–12 that adversely influences prognosis.^13–16 Treatment remains frustrating, but new approaches have been suggested based on improved understanding of mechanism that focuses on ventricular changes that displace the mitral leaflet attachments at the papillary muscle (PM) and annular level, restricting mitral leaflet closure.^{7, 8} This pattern has generally been associated with two scenarios: infarction and bulging of the inferior and posterior LV base and mid-ventricle underlying the PMs^1–12 and global LV dilatation and dysfunction which also involves the PMs and annulus.^{7, 8}

Clinical studies, however, implicate not only segmental inferobasal but also antero-apical MIs in the pathogenesis of MR and its prognostic impact,^{14, 15} raising the question about why MR occurs in such infarctions. We can propose that anterior infarct extension to the inferior apex can lead to bulging of the dilated apex, which mechanically displaces or tethers one or both papillary muscles toward the apex, even though the muscle underlying the PM base is not infarcted.¹⁷ This would in turn lead to mitral leaflet tethering and MR (Fig. 1).

Figure 1.

Proposed mechanism of ischemic mitral regurgitation (MR) induced by inferoapical dyskinesis (right), exerting traction on the adjacent papillary muscle (PM), increasing tethering length and height (TL, TH); absent (left) with only anteroapical (2 Seg) infarction. AO = aorta.

This study therefore tested the hypothesis that apical wall motion abnormality without involvement of the inferior or posterior base or mid-ventricle can cause MR with relatively preserved global LV size and systolic function. The putative mechanism is increased mitral leaflet tethering exerted by the apex. This was first tested by a retrospective clinical analysis to confirm that important MR is more frequent in patients with anteroapical MIs in whom the inferior apex is also involved. A detailed quantitative analysis of tethering mechanism was then performed in patients with antero-apical MI, comparing those with and without MR. This mechanism was confirmed in a controlled experimental large-animal model of apical infarction.

Methods

Human retrospective study

The transthoracic cardiac ultrasound database at our institution was retrospectively searched over three years. We identified 476 patients with anteroapical MIs without involvement of the inferoposterior or lateral base or mid-ventricle and without marked global LV dilatation or dysfunction (LV ejection fraction > 35%, LV diastolic diameter ≤ 60mm, LV systolic diameter ≤ 45mm). Patients with organic mitral valve changes or significant aortic valve disease were excluded. The remaining patients were divided into two groups: akinesis limited to the two anterior apical segments versus akinesis of all four apical segments, and the proportion with ≤ moderate MR in each group compared.

Human mechanistic study

Eighty patients were analyzed, divided into four groups (20 patients each):

• Group 1

  MI involving all four apical segments with important (moderate or more) MR;

• Group 2

  MI involving all four apical segments with no or minimal (< mild) MR;

• Group 3

  MI involving the anterior apical segments only, with no or minimal (< mild) MR;

• Group 4

  a normal control group of 20 consecutive patients with normal LV global and segmental function, with no evidence of other cardiac disease or MR by echocardiography or clinical records. We tested the hypothesis that MR among all these patients is predicted by the tethering length from the PM tip to the anterior mitral annulus and its dynamic change within the cardiac cycle. This dynamic change would be consistent with the concept (Fig. 1) that systolic traction on the PM transmitted by a dyskinetic apical segment diminishes the normal systolic decrease in tethering length.

The sheep mechanistic study was based on our observation that mid- to distal occlusion of the left anterior descending (LAD) artery in sheep, which typically produces an anteroapical MI without MR, occasionally produces inferior apical involvement as well, and in such instances can also produce MR with a typically restricted leaflet closure pattern in the absence of global LV dilatation and dysfunction (Beeri R et al., unpublished results). Dorsett hybrid sheep (20–30 kg) were loaded for 3 days with amiodarone (200 mg PO BID); then anesthetized with thiopentothal sodium (0.5 ml/kg), intubated and ventilated at 15 ml/kg with a 2% isoflurane and oxygen mixture. All received one dose of glycopyrrolate (0.4 mg IV) and prophylactic vancomycin (0.5 g IV) and amiodarone (150 mg IV drip over the course of the operation). Surface ECG was monitored and a sterile left thoracotomy performed with pericardial incision and creation of a cradle. After baseline echo imaging, an anteroapical MI was produced by ligating the mid- to distal LAD, known to produce a substantial MI.¹⁸ An immediate 2D echo apical image was performed to confirm that septal wall motion abnormality extends at least one-third of the way from LV apex to base for standardization. Antibiotics (Cephapirin, 0.5 gm IV) and analgesics (Buprenorphine, 0.3 mg BID) were administered for the next 5 days, and oral amiodarone (200 mg BID) for the next three. During repeat sterile thoracotomy at an average of 45±7 days, 2D and 3D echo were performed to evaluate LV remodeling and function. The animal studies conformed to NIH guidelines for animal research (Guide for the Care and Use of Laboratory Animals, National Research Council, Washington, DC, 1996) and were approved by the institutional Animal Care Committee. We compared five such sheep that developed MR with four sheep having anteroapical MI without MR from comparable LAD ligations, measuring changes in the LV and mitral valve over an average of 45 days follow-up.

Echocardiographic methods

In the patient studies, 2-D echo studies with Doppler color flow mapping were performed in standard views using a Philips Sonos 7500 machine with an S3 transducer (Philips, Andover, MA). Depth and sector settings were optimized for color Doppler resolution and MR quantification. LV end-systolic and end-diastolic volumes (LVESV, LVEDV) and ejection fraction (EF) were calculated by the biplane method of discs. In the sheep, rotated apical images were obtained at 10° intervals with a 5 MHz TEE probe (Philips Sonos 7500) gated to ECG and respiration. Digital images were analyzed on a workstation with custom programs.¹⁹ Endocardial surfaces were traced to calculate LV volumes and EF using a validated technique.²⁰ MR was initially graded semi-quantitatively (0–4) based on vena contracta dimension and jet area/left atrial area in the parasternal long axis and apical long-axis and 4-chamber views; MR assessment was later corroborated by quantitative Doppler assessment: regurgitant volume was calculated as mitral inflow minus aortic outflow, each obtained as the product of Doppler time-velocity integral with the area at the point of measurement; regurgitation fraction (RF) was calculated as regurgitant volume divided by mitral inflow volume, and verified to be ≤ 7% in patients and sheep with trace or no MR by semi-quantitative assessment.²¹

Mitral valve relationships²²

In the mechanistic patient studies, tethering length (TL) was measured at end-diastole (initial mitral valve closure) and end-systole (smallest LV cavity just prior to mitral valve opening) in the apical long-axis view (Fig. 1) from the tip of the inferior (medial) PM to the anterior mitral annular hinge point. In the sheep studies, this tethering length was measured to the medial fibrous trigone based on tracings in the rotated 3-D apical views. Tethering height (TH) was measured at end-diastole and end-systole in same view as the perpendicular from the tip of the inferior (medial) papillary PM to the line connecting the annular hinge points (Fig.1).

Statistical analysis

Data are presented as mean± SD. Data analysis was performed using SPSS (Chicago, IL). Variables were compared among patient and animal groups by analysis of variance, with 2-way t-tests among groups when positive, using the Bonferroni correction. Changes in sheep studies from baseline (pre-MI) to follow up were compared within groups by paired t-test. Comparison of proportions of moderate to severe MR among patient groups was by Chi-squared test. In each of the mechanistic human and sheep studies, multiple linear regression analysis was performed to determine the contribution of LV and mitral valve measures to MR grade (in the sheep, presence or absence of important MR), entering LVESV, LVEDV, EF, heart rate, maximal and minimal annular dimension, systolic and diastolic tethering lengths and their difference. In the human and sheep mechanistic studies (studies 2 and 3), we dichotomized MR (no to minimal versus moderate to severe) and thus used binary logistic regression. All computations were done using the SAS statistical software, version 9.12, SAS Institute Inc., Cary, NC, USA. The variables most closely related to MR severity were identified by significance in binary logistic regression, entering LVESV, LVEDV, EF, heart rate, maximal and minimal annular dimension, systolic and diastolic tethering lengths and their difference. Then, to ascertain the relative contribution of the significant variables to MR severity we used multivariate binary logistic regression, and derived the receiver operating characteristic (ROC) curves. The area under the ROC curve (AUC) was estimated for each step of the multivariate analysis.

Results

Human retrospective study

Of the 476 patients identified post anterior MI without involvement of the inferoposterior base or mid-ventricle, 234 (49%) had anterior MI involving the 2 anteroapical segments and 242 (51%) had involvement of all 4 apical segments. There was no significant difference between the groups in age (64±20 vs. 63±15 years), gender (39% vs. 49% female), BSA (1.78±0.21 vs. 1.74±0.24 m²), time post MI (1.6±0.2 vs. 1.7±0.5 months), or cardiovascular risk factor profile: diabetes mellitus (32.8% vs. 33.1%), smoking (41% vs. 43%), dyslipidemia (39% vs. 37%) and hypertension (43% vs. 39%). There was no significant difference between the groups in blood pressure (125±20/76±9 vs. 126±19/76±8 mmHg) or heart rate (75±17 vs. 74±18 bpm). LVEF was higher in the 2-segment group (46±5 vs. 41±4%, p<0.01). The group with 4 segments involved had a significantly higher MR grade (1.9±0.8 vs. 1.5± 0.8, p<0.01). Moderate-severe MR (grades 3–4) occurred nearly twice as often in the 4-segment group (17±2% vs. 9±2%, p<0.01).

Human mechanistic study (Tables 1 and 2)

Table 1.

Clinical Characteristics in Human Mechanistic Study:

	Apical MI +MR 4 SEG group (n=20)	Apical MI No or Minimal MR 4 SEG group (n=20)	Apical MI No or Minimal MR 2 SEG group (n=20)
Age (years)	74.6±10.9	67.0±13.05	68.0±12.7
Sex (F/M)	40/60	40/60	45/55
BSA (Kg/m2)	1.79±0.18	1.78±0.13	1.76±0.28
SBP (mmHg)	124.1±14.6	125.3±17.6	127.8±17.8
DBP (mmHg)	77.3±7.2	75.9±7.6	76.9±5.6
HR (bpm)	73.9±14.3	74.6±18.9	75.1±16.6
Diabetes Mellitus (%)	33.1	32.8	30.8
Smokers (%)	39.6	41.3	42.1
Dyslipidemia (%)	41	39	38
Hypertension (%)	37	38.5	41
Time After MI (months)	1.6± 0.3	1.7±0.5	1.5±0.3

SBP =Systolic Blood Pressure, DBP =Diastolic Blood Pressure, HR=Heart Rate, BSA= Body Surface Area, MI= Myocardial infarction. All P values among groups are not significant.

Table 2.

Human Mechanistic study:

	Apical MI +MR 4 SEG group (n=20)	Apical MI No or Minimal MR 4 SEG group (n=20)	Apical MI No or Minimal MR 2 SEG group (n=20)	Normal Control Group (n=20)
MR grade 0–1	0/20	20/20	20/20	20/20
MR grade 2–4	20/20	0/20	0/20	0/20
Age (years)	74.6±10.9	67.0±13.05	68.0±12.7	70.0±11.4
Sex (F/M)	40/60	40/60	45/55	60/40
BSA (Kg/m2)	1.79±0.18	1.78±0.13	1.76±0.28	1.76±0.15
LVESV (ml)	76.2±14.0	67.2±9.0 df	61.3±13.8e	34.8±14.4a,b,c
LVEDV (ml)	118.1±14.8	109.8±15.6 df	105.1±16.4	83.7±20.1a,b,c
EF (%)	35.7±6.5	38.5±4.6 df	42.9±7.6 e	57.7±7.4 a,b,c
LVEDD (cm)	4.16±0.6	4.29±0.30	4.24±0.38	4.15±0.68
LVESD (cm)	2.9±0.47	2.91±0.28	2.88±0.28	2.62±0.39
Annulus max (cm)	3.42±0.37	3.48±0.20	3.45±0.14	3.31±0.12
Annulus min (cm)	3.04±0.28	3.09±0.13	2.97±0.19	2.79±0.34
Annulus change (cm)	0.38±0.23	0.39±0.21	0.47±0.16	0.42±0.22
TL-Diast (cm)	4.39±0.59	4.15±0.42 d	4.11±0.18 e	3.70±0.23 a
TL-Syst (cm)	4.11±0.57	3.36±0.40 d	3.14±0.12 e	3.01±0.21 a
TL: ED-ES	0.29±0.29	0.79±0.49 d	0.95±0.06 e	0.69±0.02 a
TH-Diast (cm)	3.56±0.47	3.23±0.49 d	3.05±0.12 e	3.07±0.21 a
TH-Syst (cm)	3.27±0.51	2.66±0.44d	2.58±0.31 e	2.48±0.26 a
TH: ED-ES	0.29±0.12	0.57±0.42d	0.47±0.11e	0.49±0.15 a

^a4-Segments+MR vs. Normal, p<0.01

^b4-Segments-MR vs. Normal, p<0.01

^c2-Segments vs. Normal, p<0.01

^d4-Segments+MR vs. 4-Segments-MR, p<0.01

^e4-Segments+MR vs. 2-Segments, p<0.01

^f4-Segments-MR vs. 2-Segments, p<0.01

Left ventricular end-systolic volume (LVESV), end-diastolic volume (LVEDV), ejection fraction (EF), end-systolic diameter (LVESD), end-diastolic diameter (LVEDD), tethering length and height in systole and diastole (TL, TH, Syst, Diast) and their changes (ED-ES). MR grade: grades 0–1 (no or minimal MR) versus grades 2–4 (significant MR: moderate or greater).

There were no significant differences in age, gender, or BSA among all the groups. Within the MI groups, there were no significant differences in time post MI, blood pressure, heart rate or cardiovascular risk factor profile. Patients with 4-segment involvement and MR (Group 1) demonstrated apical leaflet tethering with bulging dyskinesis of the inferior apical wall despite maintained thickening of the basal and mid-ventricular LV wall (double-headed arrows, Figs. 2A, 2B), accompanied by MR through the tethered leaflets (Fig. 2C). The PM tip was visibly retracted toward the bulging inferior apex, exceeding its normal apical excursion. Quantitatively this corresponded to an important increase in systolic tethering length (4.1±0.6 cm vs. 3.3±0.4 cm in group 2 with MI involving 4 segments with no MR, and also vs. 3.1±0.1 cm in group 3 with MI involving the anterior apical segments only and 3.01±0.2 cm in the control group, p<0.01). Diastolic tethering length was also increased only in group 1 with inferoapical dyskinesis. The normal systolic decrease in tethering length accompanying ventricular emptying was virtually eliminated in group 1 with 4 apical segment involvement and MR, consistent with systolic retraction of the PM tip away from the annulus (Fig. 3), but preserved in group 2 with 4 apical segment involvement without MR, who had no inferoapical dyskinesis, and in the 2 apical segment group with no or minimal MR.

Figure 2.

2A,B: Patient with 4-segment apical infarction, inferoapical dyskinesis and anteroapical bulging (outward arrows), and mitral leaflet tenting toward the apex despite thickening of the inferior wall at the base and underlying the PM (double-headed arrows). 2C: Apically tented leaflets, moderate MR in this patient.

Figure 3.

Human mechanistic study: Patients with 4-segment apical infarction have increased tethering length versus 2-segment infarction and normals, with obliteration of the normal systolic decrease in tethering length.

Tethering height (TH), the component of TL parallel to the LV long axis and perpendicular to the annulus, was also higher in the MR group in systole and diastole, with a blunted systolic decrease.

LVEF was lower in group 1 with 4 segment involvement and MR than in group 2 with 4 segment involvement without MR (35.7±6.5% vs. 38.4± 4.6%, p<0.01), who in turn had a lower EF than the 2 segment group (42.9±7.6%, p<0.01). The same trends were seen for LV volumes, which were largest in patients with 4 segments and MR (p<0.01, Table 2).

Binary logistic regression analysis showed that the presence of moderate or greater MR was predicted by tethering length and its systolic change, with ROC contributions (AUC) of 0.74 and 0.71, respectively, with no significant contributions from LVEF, LV volume, or annular size.

Sheep mechanistic study (Table 3)

Table 3.

Sheep mechanistic study

	MR n=4		Control n=5
	Before MI	After MI	Before MI	After MI
LVESV (ml)	16.2 ± 1.9	28.7 ± 4.3a	19 ± 4.7	27.0 ± 5.4 b
LVEDV (ml)	40.6 ± 2.1	49.8 ± 2.9 a	45.1 ± 8.3	51.9 ± 11.3
EF (%)	60.2 ± 3	42.6 ± 5.2 a	57.3 ± 4	47.4 ± 5.3 b
LVEDD (cm)	4.3±0.2	4.1±0.2	4.0±0.2	4.2±0.3
LVESD (cm)	3.1±0.1	3.1±0.3	3.0±0.3	3.1±0.2
Annulus max (cm)	3.0 ± 0.1	3.0 ± 0.1	2.9 ± 0.1	2.9 ± 0.1
Annulus min (cm)	2.9 ± 0.2	2.9 ± 0.1	3.0 ± 0.2	3.0 ± 0.1
Annulus change (cm)	0.1 ± 0.1	0.1 ± 0.1	0.1 ± 0.1	0.1 ± 0.1
TL-Diast (cm)	2.6 ± 0.5	3.0 ± 0.4	2.3 ± 0.3	2.5 ± 0.3c
TL-Syst (cm)	2.1 ± 0.4	2.9 ± 0.4 a	2.0 ± 0.4	2.1 ± 0.3c
TL: ED-ES	0.6 ± 0.2	0.2 ± 0.1 a	0.4 ± 0.3	0.5 ± 0.2c
TH-Diast (cm)	1.9 ± 0.2	2.5 ± 0.5	1.8 ± 0.5	1.9 ± 0.6
TH-Syst (cm)	1.8 ± 0.2	2.4 ± 0.5 a	1.7 ± 0.5	1.8 ± 0.5
TH: ED-ES	0.2 ± 0.1	0.1 ± 0.1	0.2 ± 0.1	0.2 ± 0.2

^aMR group, After vs. Before MI, p<0.01

^bControl group, After vs. Before MI, p<0.01

^cMR versus Control, After MI, p<0.01

Abbreviations as in Table 2.

As in the human mechanistic study, animals that developed MR showed preserved thickening of the inferoposterior wall at the base and mid-ventricle with dyskinesis of the anterior and inferior apex (Fig. 4) and prominent systolic apical retraction of the PM tip, compared with only anteroapical bulging in the animals without MR. In the sheep who developed MR, the average regurgitant volume was15.4±1.5 ml and the average RF was 28.8±4.5% (moderate). There were no significant differences in the baseline characteristics of both groups, including LVESV, LVEDV, LVEF, HR, LVES and ED diameter at the base, mitral annular dimensions, or systolic and diastolic tethering lengths. In both groups, the LV remodeled to a comparable extent over 45±7 days, with no significant differences in LV volumes at follow up and a lower but not significantly decreased EF in the MR group (42.6±5.2 vs. 47.4±5.3%, p=NS). Systolic tethering length increased to a significantly greater extent over time in the MR group (by 0.8 vs. 0.1cm, p<0.001, Fig. 5A). At follow up, the normal systolic shortening of tethering length was virtually eliminated in the MR group consistent with systolic PM retraction toward the apex (Fig.5B). The same changes pertained to tethering height. Logistic regression analysis showed that the presence of moderate or greater MR was predicted by systolic tethering length (AUC=0.62), without significant contributions from LV volume, EF, or annular dimensions.

Figure 4.

Sheep with inferoapical dyskinesis and anteroapical bulging (arrows) causing apical tenting of the mitral leaflets despite continued contraction of the inferior segments at the base and underlying the PM (inward arrows).

Figure 5.

Figure 5A. Sheep developing MR after apical infarction (left) showed increased systolic tethering length (STL) over 1.5 months, not seen in sheep without MR (no inferoapical involvement).

Figure 5B. At 1.5 months post-infarction, sheep developing MR had larger tethering lengths in systole and diastole, with obliteration of the normal systolic decrease.

Discussion

Incomplete mitral leaflet closure (IMLC) with apically restricted leaflet coaptation is the final common pattern of ischemic or functional MR in LV dysfunction, with increased tethering length from an affected PM to the opposite mitral annulus being its strongest predictor in a variety of clinical and experimental settings.²² Until now, in the absence of global LV dysfunction and dilatation, it has widely been considered to result from contractile abnormalities localized to the infero-posterior LV base and mid-ventricle; it has the potential, in turn, to exacerbate LV remodeling in a vicious cycle of MR increasing MR.²³ This study demonstrates that PM displacement caused by the mechanical influence of an adjacent bulging apex, with dyskinesis extending from the anterior to the inferior apical wall, can also create incomplete mitral leaflet closure and MR. MR in this setting also correlates best with systolic tethering length from PM tip to annulus, and the normal decrease in tethering length as ventricular cavity size decreases in systole is blunted or lost because of apical PM retraction. This mechanism is well illustrated by three-dimensional endocardial reconstruction from a more recent patient with moderate IMR despite evident contraction of the inferior base and mid-ventricle (Fig. 6, left, comparing the end-systolic cavity with the end-diastolic mesh), but with bulging dyskinesis of the apex, including its inferior segments.

Figure 6.

Example of 57 year-old woman with ischemic MR despite inward contraction of the inferior segments at the base and mid-LV regions underlying the PMs, as seen on the left: 3D echo comparison of end-diastolic (open mesh) and end-systolic LV endocardial surfaces. Inferoapical as well as anteroapical bulging is seen (outward arrows).

This study was motivated by clinical and experimental observations that led to quantitative studies of mechanism, after a database review confirmed the higher frequency of moderate to severe MR in patients with anterior apical involvement. The mechanistic studies confirmed the relationship between MR, tethering length, and its dynamics, and also showed by 3D echocardiography that these changes evolve over time from a normal baseline in a controlled experimental model.

Mechanistic implications and correlates

These results further confirm that MR does not result from PM dysfunction alone,^{4, 24} or even dysfunction of the myocardium underlying a PM²⁵, but rather, PM tip position relative to the mitral annulus. This confirms the mechanistic postulate of Sabbah et al.⁷ that distortions in LV shape, as opposed to nonspecific increases in volume or decreases in EF, play a central role in displacing the PM and disrupting coaptation. The comparison of patients with and without MR despite involvement of the same 4 apical segments is particularly instructive: MR was determined by inferoapical dyskinesis, increasing tethering length and decreasing its systolic shortening in the patients with MR.

In this context, important MR developed despite relatively preserved LV size and function, and the contribution of LVEF to MR was modest. While patients with 4-segment apical involvement would be expected to have greater LV remodeling, that is not well represented by the gross global measures of LV volume and EF, but is expressed by geometric changes in tethering length in systole and diastole that reflect localized apical remodeling. This further confirms the strong relationship between ischemic MR and localized LV remodeling, also seen with inferobasal MI, as well as the particular predisposition of the apex to remodel, as reported by Picard et al.

Clinical implications

This study expands our understanding of the spectrum of location, chronicity and severity of LV dysfunction underlying ischemic MR; it may emphasize the contribution of IMR to adverse prognosis even in patients with anterior MI independent of global LV dysfunction. This mechanism has practical implications because localized change should be susceptible to localized geometric treatments, by analogy to observations with infarctions at the base of the heart in which an adjustable localized patch, or polymer injection, can be titrated to eliminate ischemic MR.^{26, 27} Our findings can also be a considered in decisions regarding the potential benefit of revascularization in acute antero-apical infarction. A strong theme in the surgical literature on LV reconstruction has been the influence of apical aneurysm repair on concomitant MR. Mickleborough’s group, for example, have shown that a modified linear closure excision repair of dyskinetic or akinetic LV aneurysms provides symptomatic relief of heart failure and good long-term survival, improved LV function and decreased MR, a strong predictor of mortality, in 57% of patients imaged by ultrasound.²⁸ The procedure realigns the PMs in order to reduce MR, as do reconstructive approaches of Kron, Menicanti and colleagues.^{29, 30} Approaches that may benefit patients with more limited apical expansion causing MR may include limiting LV size or tethering with increased apical pericardial restraint, with myoplasty to wrap skeletal muscle around the apex, with infarct plication or apical bulging excision to reduce tethering force³¹, or with leaflet or chordal elongation or modification.³²

Limitations and future directions

The clinical spectrum of ischemic MR is varied, and although this study explores one component of that spectrum not previously recognized, it importantly increases our understanding of common themes and potential therapeutic targets. This study is retrospective in nature and aims to describe the mechanism of this phenomenon, rather than to assess its prevalence. Its existence suggests that it should be addressed when new therapies are formulated.

Conclusions

Anterior MI with dyskinetic inferoapical extension can mechanically displace the papillary muscles as an expression of localized LV remodeling, causing ischemic MR in the absence of prominent global LV dysfunction or dilatation or of typical inferobasal abnormalities. This suggests the possibility of repositioning treatments for this condition.