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Microanatomy of Human Left Ventricular Coronary Veins.

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THE ANATOMICAL RECORD 292:23–28 (2009)
Microanatomy of Human Left
Ventricular Coronary Veins
1
SARA E. ANDERSON,1,2 ALEXANDER J. HILL,3 AND PAUL A. IAIZZO1,2*
Department of Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota
2
Department of Surgery, University of Minnesota, Minneapolis, Minnesota
3
Medtronic, Inc., Minneapolis, Minnesota
ABSTRACT
We describe analyses of the microanatomy of major left ventricular
veins, including their relationship to the myocardium. Immediately following fixation of six fresh human hearts, anterior interventricular veins
(AIV), left marginal veins (LMV), posterior veins of the left ventricle
(PVLV), and posterior interventricular veins (PIV) were sectioned in
5 mm intervals perpendicular to the veins’ length from base to apex.
Slides were prepared, digitized, and analyzed; measurements were made
of each vein’s wall thickness, circumference, distance between vein wall
and myocardium, and distance between vein wall and closest artery. For
analyses, based on the length of each vein, slides were grouped into three
regions: basal (top third), mid (middle third), and apical (bottom third).
Vein wall thicknesses and circumferences were significantly smaller (P <
0.05) in apical than basal regions in all veins. Vein wall thicknesses were
significantly larger in the AIV and PIV than in the LMV and PVLV (P <
0.05). The AIV was significantly farther away (1.81–2.99 mm) from the
myocardium than the other three veins (P < 0.05). Left ventricular venous microanatomy was quantified and analyzed. Variation in venous
microanatomy, including distance between vein walls and excitable
myocardium, could impact therapies involving the coronary venous system. Anat Rec, 292:23–28, 2009. Ó 2008 Wiley-Liss, Inc.
Key words: veins; coronary; microanatomy; left ventricle;
human
INTRODUCTION
MATERIALS AND METHODS
The coronary venous system has been employed in a
variety of methods to enhance cardiac therapies because
of the venous system’s ‘‘dense meshwork with numerous
interconnections’’ and absence of atherosclerotic disease
effects (Mohl, 1994). Most recently, the coronary venous
system has been targeted as a pacing lead implant site
for cardiac resynchronization therapy via biventricular
or left ventricular (LV) pacing. Specifically, because of
increased clinical indications for cardiac resynchronization therapy relative anatomy of the LV coronary veins
have become more clinically relevant because of their
close proximity to LV myocardium. However, the specific
microanatomy of these veins remains largely unexplored. Therefore, the purpose of this study was to perform detailed analyses of the microanatomy of the major
LV veins in the human heart.
Fresh human hearts (n 5 6) were obtained via the
generous donation of individuals and their surviving
family members, bequeathed through the University of
Minnesota Anatomy Bequest Program. Each fresh heart
(24–48 hr postmortem) was perfusion fixed in a pressurized perfusion fixation chamber (10% formalin).
Ó 2008 WILEY-LISS, INC.
*Correspondence to: Paul Iaizzo, Ph.D., Department of
Surgery, University of Minnesota, B172 Mayo, MMC 107, 420
Delaware Street SE, Minneapolis, MN 55455. Fax: 612-6242002. E-mail: iaizz001@umn.edu
Received 30 January 2008; Accepted 20 April 2008
DOI 10.1002/ar.20766
Published online 24 October 2008 in Wiley InterScience (www.
interscience.wiley.com).
24
ANDERSON ET AL.
Fig. 1. Heart model diagrams show the typical locations of the left ventricular veins: anterior interventricular vein along the anterior interventricular sulcus, the left marginal vein along the left margin of the
heart, the posterior vein of the left ventricle along the posterolateral wall, and the posterior interventricular
vein along the posterior interventricular sulcus.
Perfusion fixation involved cannulating the superior
vena cava, pulmonary trunk, aorta, and one pulmonary
vein. The heart was submerged in a container of formalin, and the great vessels were connected to a formalinfilled upper chamber. Formalin was continuously
pumped to the upper chamber and was forced by gravity
into the heart through the cannulated vessels. The
height of the upper chamber corresponded to physiologic
pressures observed by the heart and thus fixed the
hearts in an end-diastolic shape. After the hearts were
perfusion fixed for at least 48 hr, the anterior interventricular veins (AIV), left marginal veins (LMV), posterior
veins of the left ventricle (PVLV), and posterior interventricular veins (PIV) were dissected into blocks and
then sectioned along the length of each vein in 5 mm
intervals perpendicular to the veins’ length from base to
apex (Fig. 1). Standard histological methods were used
to prepare slides using Masson’s trichrome stains. Slides
were then digitized (Super Coolscan1, Nikon, Melville,
NY) and analyzed (Image-Pro1 Plus 4.1.0, Media Cybernetics1, Bethesda, MD). Measurements were made of
each vein’s wall thickness and circumference and distances between the vein walls and the adjacent myocardium
(Fig. 2). Vein wall thickness was measured at 12 positions around the circumference of the vein and then
averaged to yield an average vein wall thickness for
each slide. Vein circumference was measured by tracing
the inner lumen of the vein walls. Distance between the
vein walls and myocardium was measured in eight
approximately equal increments along each vein wall to
yield an average distance to the myocardium for each
slide. Distance between the vein and the nearest artery
was measured by choosing the shortest distance between
the vein and the nearest artery. A single investigator
performed all histological measurements to minimize
variability in measurement technique.
The total number of slides for a given vein was divided by three to yield basal (top third), mid (middle
third), and apical (bottom third) groups for each vein.
For instance, in one heart, the PVLV was sectioned into
19 slides, whereas in another heart, the PVLV was
divided into 13 slides. For the first heart, the first six
slides comprised the basal section, the next seven comprised the mid section, and the final six comprised the
apical section, whereas for the second heart, the first
four slides comprised the basal section, the next five, the
mid section, and the final four, the apical section.
Relative regional differences in vein wall thickness,
vein circumference, distance to the myocardium, and
distance to arteries were compared using analyses of
variances (ANOVA); when the ANOVA was significant
(P < 0.05), a Bonferroni multiple comparison correction
was also performed. Correlation tests (Prism 3.01,
GraphPad Software, San Diego, CA) were used to determine if vein wall thickness and vein circumference were
correlated. All data are presented as mean 6 1 SD.
RESULTS
Five hearts had all four commonly described major LV
veins; one heart did not have an LMV (Fig. 1). Two of
the six hearts were considered normal or free of cardio-
HUMAN CORONARY VENOUS MICROANATOMY
25
Fig. 2. Example of measurements made on a digitized slide of a posterior interventricular vein (PIV).
Measurements include vein wall thickness, vein circumference, distance to the myocardium, and distance
to the closest artery.
myopathies (Table 1); however, no significant differences
were observed between normal and diseased hearts.
Vein length varied from 60 to 215 mm (n 5 23). Table 2
provides a summary of average vein lengths, average
vein wall thicknesses, average vein circumferences, and
average distances to the myocardium in each region of
the four veins; Fig. 3 shows representative examples of
each vein in both basal and apical regions.
In general, AIV and PIV vein wall thicknesses were
significantly larger when compared with LMV and PVLV
vein wall thicknesses (P < 0.05). For example, in the basal region of one heart, the average vein wall thicknesses were 0.19 mm for the AIV and 0.15 mm in the
PIV, in comparison with 0.09 mm for the LMV and 0.10 mm
in the PVLV. Vein wall thicknesses in apical regions of all
four veins were significantly smaller than those in basal
regions (P < 0.05). Average vein wall thicknesses in apical
regions ranged from 0.09 6 0.03 mm to 0.13 6 0.04 mm,
in comparison to 0.11 6 0.03 mm to 0.17 6 0.04 mm in
basal regions. The overall circumference of the PIV was
significantly larger than all other veins (P < 0.05). More
specifically, average vein circumferences for the mid
region PIV were 11.19 6 3.68 mm (diameter 5 3.56 6
1.17 mm), whereas association circumference measurements were 7.07 6 3.27 mm (diameter 5 2.25 6 1.04 mm)
in the AIV, 6.43 6 1.89 mm (diameter 5 2.05 6 0.60 mm)
in the LMV, and 5.95 6 1.43 mm (diameter 5 1.89 6 0.46
mm) in the PVLV. Average vein circumferences in apical
regions were significantly smaller (ranging from 4.57 6
1.83 mm to 8.13 6 4.27 mm; diameters from 0.73 6 0.58
mm to 2.59 6 1.36 mm) than in both mid and basal
regions, which combined, ranged from 5.95 6 1.43 mm to
13.26 6 3.34 mm (diameters from 1.89 6 0.46 to 4.22 6
1.06 mm, P < 0.05, Table 2).
The AIV was significantly farther away from the adjacent myocardium than the other three veins (P < 0.05).
For example, in basal regions, the average distance
between the AIV and the myocardium was 2.90 6 1.22
mm, whereas the average distances to the myocardium
were 1.44 6 1.09 mm for the LMV, 1.60 6 2.16 mm for
26
ANDERSON ET AL.
TABLE 1. Patient demographic information
Age
(years)
Gender
Weight
(lbs)
Heart
weight (g)
53
M
N/A
n/a
63
F
250
600
64
68
F
F
125
165
369
n/a
81
94
F
F
105
140
697
655
Disease state
Idiopathic cardiomyopathy, atrial fibrillation,
hyperthyroidism, pulmonary hypertension, chronic
anticoagulation
Cardiac arrest, COPD, chronic emphysema (heavy
smoker), lung cancer
Leukemia
CHF, COPD, appendectomy, Type II diabetes, hip
replacement, hyperlipidemia, hypertension,
hyperthyroidism, kidney removed, renal disease, renal
failure
Cerebral vascular accident, dehydration
CHF, atrial fibrillation, hypertension, mitral valve
disorder, osteoporosis
COPD, chronic obstructive pulmonary disease; CHF, congestive heart failure.
TABLE 2. Summary of left ventricular coronary veins in human hearts (n 5 6)
AIV (n 5 6)
Average length (mm)
Average vein wall thickness (mm)
Average vein circumference (mm)*
Average vein diameter (mm)
[computed from circumferences]
Average distance to myocardium
(mm)***
Average distance to nearest artery
(mm)y
Base
Mid
Apex
Base
Mid
Apex
Base
Mid
Apex
Base
Mid
Apex
Base
Mid
Apex
113
0.17
0.15
0.11
9.26
7.07
4.57
2.95
2.25
1.46
2.90
2.13
1.70
3.22
3.84
3.74
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
54
0.04
0.04
0.06
1.73
3.27
1.83**
0.55
1.04
0.58
1.22
1.54
1.64
1.51
1.90
1.36
LMV (n 5 5)
PVLV (n 5 6)
103
0.13
0.12
0.09
6.28
6.43
4.80
2.00
2.05
1.53
1.44
1.23
1.46
3.11
2.37
2.89
88
0.11
0.10
0.11
6.77
5.95
6.39
2.15
1.89
2.04
1.60
1.00
1.42
2.47
2.36
2.67
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
51
0.07
0.04
0.03
1.76
1.89
1.43**
0.56
0.60
0.45
1.09
1.13
1.60
2.17
1.83
2.02
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
20
0.03
0.04
0.04
3.00
1.43
2.38**
0.95
0.46
0.76
2.16
0.96
0.75
1.45
0.72
1.17
PIV* (n 5 6)
89
0.16
0.14
0.13
13.26
11.19
8.13
2.15
3.56
2.59
1.31
0.41
0.56
2.14
1.43
1.53
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
19
0.10
0.05
0.04
3.34
3.68
4.27**
1.06
1.17
1.36
1.20
0.29
0.41
1.25
0.23
0.53
AIV, anterior interventricular vein; LMV, left marginal vein; PVLV, posterior vein of the left ventricle; PIV, posterior interventricular vein.
*P < 0.05 PIV vs. AIV, LMV, and PVLV.
**P < 0.05 vs. mid and basal regions within the same vein.
***P < 0.05 AIV vs. LMV, PIV, and PVLV.
y
P < 0.05 AIV vs. PIV.
the PVLV, and 1.31 6 1.20 mm for the PIV. Distances
between veins and the myocardium did not vary significantly by region (Table 2).
The AIV was significantly farther away from the nearest artery than the PIV (P < 0.05). For instance, average
distance between the nearest artery and the mid region
was 3.84 6 1.90 mm and 1.43 6 0.23 mm for the AIV
and PIV, respectively. Distance between the vein and the
nearest artery did not significantly vary when compared
by region.
DISCUSSION
To our knowledge, the microanatomy of the coronary
venous system has not been extensively examined with
respect to needs associated with current clinical practices. Although the sample size in this study was small,
obtaining whole fresh human heart specimens is a rare
occurrence. Additionally, the small sample size could
account for no significant differences in any microanatomical measurements between normal and diseased
hearts. This study provides two principal findings
regarding LV venous microanatomy that could have important implications for LV coronary venous pacing lead
placement: (1) vein circumferences increased from apical
to basal regions and (2) the distances between a given
vein and the myocardium did not vary significantly
among regions.
Smaller pacing thresholds are required to consistently
capture myocardial excitation in apical positions in comparison to basal positions (Daubert et al., 1998; Huang
et al., 2002). Additionally, depending on pacing lead
design, implanting a lead more distally in a vein has the
potential added benefit of increased long-term stability
HUMAN CORONARY VENOUS MICROANATOMY
Fig. 3. Representative examples of an anterior interventricular vein (AIV) in basal (A) and apical (B)
regions, left marginal vein (LMV) in basal (C) and apical (D) regions, posterior vein of the left ventricle
(PVLV) in basal (E) and apical (F) regions, and posterior interventricular vein (PIV) in basal (G) and apical
(H) regions. Scale applies to all examples.
27
28
ANDERSON ET AL.
(Hansky et al., 2002). Lower pacing thresholds and
greater lead implant stability in more apical regions of
coronary veins have been assumed to be associated with
smaller vein circumferences. However, although distance
between a given vein and the myocardium did not vary
significantly among regions, in the two most commonly
targeted veins for cardiac resynchronization therapy, the
LMV and PVLV, it was noted that these veins were
closer to the myocardium in the mid-ventricular region
than in the basal or apical regions. Yet, although the apical distances from the myocardium were greater than
the mid-ventricular distances in the PVLV, they were
still smaller than the basal distances; this supports the
finding of the reported lower thresholds seen in these
implant locations (Huang et al., 2002) and would suggest
that stable positions from the mid-ventricular to apical
regions are preferred because of the proximity to the
myocardium. When individual vein characteristics are
examined for lead implant stability (e.g., vein circumference) and low pacing threshold (distance to myocardium), it is apparent that implants in the PIV would
most likely be more stable in the apical region because
of the relatively larger vein circumferences seen in the
mid and basal regions. This position would also suggest
low thresholds because of its relatively small vein to
myocardium distance. In contrast, the data suggest that
the preferred implant location in the PVLV would be the
mid-ventricular region, because of the smaller vein circumference and smaller vein to myocardium distance,
although apical placements would also be acceptable
(Table 2). Knowledge of vein dimensions in these apical
locations is important to consider in pacing lead design.
Although the LV coronary veins are commonly utilized
in cardiac resynchronization therapy, an optimal and
universal implant site has not been identified and may
need to be individually optimized (Gasparini et al., 2003;
Albertsen et al., 2005; Gold et al., 2005). The purpose of
this study was to explore the microanatomy of the LV
coronary veins in an effort to better define anatomical
features that could enhance left heart lead placement or
other therapy delivery. Because of widely varying anatomy, it is important to continue to investigate the microanatomy of the LV veins to facilitate finding an optimal
anatomical site for therapy delivery. Future studies
should also focus on relative anatomical changes that
occur with aging, disease, and/or body mass indices.
Nevertheless, this dataset provides several unique
insights on general coronary venous anatomy.
ACKNOWLEDGMENTS
The authors sincerely thank the University of Minnesota Anatomy Bequest Program for their assistance with
this study and the generous individuals and families
who, by donating their hearts for research, made this
study possible. They also thank Louanne Cheever for
preparing the slides, Monica Mahre for assistance with
manuscript preparation, and Jason Quill for assistance
with the figures.
LITERATURE CITED
Albertsen AE, Nielsen JC, Pedersen AK, Hansen PS, Jensen HK,
Mortensen PT. 2005. Left ventricular lead performance in cardiac
resynchronization therapy: impact of lead localization and complications. Pacing Clin Electrophysiol 28:483–488.
Daubert JC, Ritter P, Le Breton H, Gras D, Leclercq C, Lazarus A,
Mugica J, Mabo P, Cazeau S. 1998. Permanent left ventricular
pacing with transvenous leads inserted into the coronary veins.
Pacing Clin Electrophysiol 21:239–245.
Gasparini M, Mantica M, Galimberti P, Bocciolone M, Genovese L,
Mangiavacchi M, Marchesina UL, Faletra F, Klersy C, Coates R,
Gronda E. 2003. Is the left ventricular lateral wall the best lead
implantation site for cardiac resynchronization therapy? Pacing
Clin Electrophysiol 26:162–168.
Gold MR, Auricchio A, Hummel JD, Giudici MC, Ding J, Tockman
B, Spinelli J. 2005. Comparison of stimulation sites within left
ventricular veins on the acute hemodynamic effects of cardiac
resynchronization therapy. Heart Rhythm 2:376–381.
Hansky B, Guldner H, Vogt J, Minami K, Tenderich G, Horstkotte
D, Korfer R. 2002. Coronary vein leads for cardiac pacing in
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Surg 50:120–121.
Huang J, Walcott GP, Killingsworth CR, Smith WM, Kenknight
BH, Ideker RE. 2002. Effect of electrode location in great cardiac
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