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Original Contribution
Review
Myocardial Venous Drainage: From Anatomy to Clinical Use
Dario Echeverri, MD, Jaime Cabrales, MD, Alejando Jimenez, MD
Abstract: The heart’s venous drainage system has been the object of observations and research for several centuries. Its anatomic
and histological characteristics, as well as its distribution and architecture, make the cardiac venous system a uniquely organized structure within the organism. An understanding of its physiology helps
in comprehending some of the mechanisms by which, under special
conditions, the myocardium tolerates ischemia. The heart’s venous
system has become important today as a route for administering pharmacologic therapy, gene therapy, growth factors, and stem cells to the
myocardium. Access through the coronary sinus is a common practice
in modern electrophysiology.
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J INVASIVE CARDIOL 2013;25(2):98-105
retrograde perfusion for maintaining nutritional supply of the
myocardium during periods of anoxia or cardioplegia has been
routinely used in cardiovascular operating rooms.
Studies of the heart’s vascular anatomy have focused mainly
on the arterial segment with marked emphasis on the coronary
arteries and myocardial capillaries; in contrast, the cardiac venous
system has traditionally been forgotten. The studies described in
the literature in the last decades are very scarce and have been
limited to anatomy and topography of the CS and its related
veins. In this sense, the new requirements for diagnosis and treatment in current cardiologic clinical practice require crossing the
frontier, making the use of selective CS catheterization techniques a routine practice since the year 2000. The advances in
diagnostic cardiac images and the improvements in angiography
have permitted a better visualization of the venous segment of
the cardiac circulation, facilitating the recently published angiography and computed tomography descriptions. The presence
of accessory pathways of the conduction system in the vicinity of
the CS has been shown since 1978, which causes electrophysiology groups to be more familiar with this structure and frequently
requires selective catheterization of the same as part of diagnostic
or therapeutic studies.
The purpose of this document is to review generalities of the
coronary venous system anatomy and the techniques used for its
selective catheterization. It is motivated by the appearance of innovative percutaneous procedures that require intervention of the
venous system, which has generated a growing interest in methods for accessing the heart’s venous circulation for coronary or
structural interventionalism in the area of hemodynamics or for
stimulation or therapeutic ablation in the area of electrophysiology.
In patients where traditional techniques for myocardial revascularization are not feasible, procedures based on catheterization of
coronary veins and retroperfusion (which can supply the minimal
metabolic needs), have been proposed, arising as alternative treatment modalities. In addition, the use of the coronary venous system has allowed regional administration of drugs, cells, and genes
for protecting and regenerating the sick myocardium.
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Key words: ablation, arrhythmias, catheterization, circulation, veins
Advances in medicine have allowed the development of useful diagnostic tests for recognizing and evaluating viable myocardial territory, which have decreased oxygen consumption
to a minimum in order to maintain minimal cellular function
and inhibit their contractile activity. The available treatment
alternatives, which include pharmacologic therapies, coronary
bypass surgeries, and various percutaneous procedures, have allowed the recovery of this viable and ischemic myocardium,
significantly impacting the recurrence of ischemic symptoms,
functional capacity, quality of life, and, ultimately, the survival
of patients with ischemic coronary disease. We must remember
the great lability of these cells with small changes in oxygen
concentration and the importance the venous system assumes
in maintaining cellular homeostasis.
Over a century ago, in 1898, Pratt1 first described the retrograde myocardial perfusion techniques that protect hypoperfused myocardial cells through catheterization of the coronary sinus (CS) and the veins related to the ischemic territory.
Pratt, a physiologist, was the first to publish this experimental
technique with results in animal models. However, his results
lacked acceptance at the time, and unfortunately, were practically forgotten. It was Beck et al, in 1948,2 who rediscovered
this simple, but marvelous idea, resuming part of Pratt’s research and perfecting the model with results that led to recommending its application in clinical practice. In the last decades,
From the Fundacion Cardioinfantil, Bogota, Colombia.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Echeverri is on the Medtronic speaker’s
bureau and board, and is a consultant for Biotoscana. The other authors report no
conflicts of interest regarding the content herein.
Manuscript submitted June 29, 2012, provisional acceptance given July 26, 2012,
final version accepted August 8, 2012.
Address for correspondence: Dr Dario Echeverri, FACC, Fundación Cardioinfantil,
Bogota, Colombia, Calle 163 #13b – 60 Hemodinamia, Bogota, Colombia. Email:
[email protected]
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Cardiac Venous System
Knowledge of epicardial venous anatomy is essential for the success of CS and cardiac vein catheterization. The venous anatomy of
the heart and its common variants has been described in detail in
autopsies and in vivo studies,3 where the majority of blood returns
to the heart through the epicardial coronary veins, then progressively
joins into larger conduits and ultimately flows into the right atrium
through the CS. Tests carried out on coronary venous system molds
show that the myocardial veins flow perpendicular to the surface of
the ventricles to empty into the epicardial veins4 (Figure 1).
The Journal of Invasive Cardiology®
Myocardial Venous Drainage: From Anatomy to Clinical Use
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Figure 1. Schematic representation of the distribution pattern of the cardiac venous system and its tributary vessels. Modified from Lüdinhhausen MV. The venous drainage of the human myocardium. In: Advances
in Anatomy, Embryology, and Cell Biology. Heidelberg, New York.
Springer. 2003:4.
The course of the anterior interventricular vein is parallel to
the anterior descendent artery and flows adjacent to it over the
interventricular septum toward the base of the heart, where it
turns laterally toward the circumflex artery to become the great
cardiac vein. The anterior interventricular vein has been analyzed
using imaging techniques, and its diameter is similar to that of
the artery. The great cardiac vein usually gathers affluents from
the left ventricular surface through the anterior interventricular
vein, a left marginal vein and a posterior left vein.8 In the inferior
wall, at the atrioventricular sulcus, the great cardiac vein flows
into the CS. The middle cardiac vein can be seen in the posterior
interventricular sulcus, often together with the posterior descendent artery and also flows directly into the CS (Figure 2).
Recently, after detailed angiographic studies, several groups
have tried to describe the coronary venous anatomy;9 the number and location of the cardiac veins turned out to be variable
in these patients. In a study by Meisel et al,10 the anterior interventricular vein and the middle cardiac vein were visible in 85
of 86 patients. However, the anatomy of the lateral marginal
vein is more variable, present in 71 of 86 patients.
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Transverse sections of the left ventricular heart wall have
shown three venous vascularization zones, which, described
from epicardium to endocardium, are: (1) external epicardial
zone, which includes a thin external layer, approximately 1
mm thick, over the walls of the left ventricle; (2) middle subepicardial zone, which together with the external zone makes
up more than 70% of the ventricular wall and the adjacent interventricular septum; and (3) internal subendocardial zone,
which makes up the rest of the ventricular wall and interventricular septum.5 In the right ventricular walls, only two
zones have been identified: (1) external epicardial zone over
the external layer of the right ventricle; and (2) thick internal
zone, which is the sum of the middle subepicardial and subendocardial zones.
Based on these findings, anatomists, physiologists and cardiologists have divided the venous system of the cardiac circulation in three parts: (1) greater cardiac venous system (major
– GCVS); (2) Smaller cardiac venous system (minor – SCVS);
and (3) intramyocardial sinusoid system.6,7 Venous filling of all
the ventricular wall zones is dependent on perfusion pressure.
Pressures below 50 mm Hg allow filling only of external veins
and the middle zone, while pressures above 80 mm Hg allow
venous filling of all myocardial ventricular zones.5
Greater Cardiac Venous System (GCVS)
The vessels of this system are located within the subepicardial layer with extensions over the atrial and ventricular surface. Frequently, its veins do not follow the topographic borders
marked by the coronary arteries.
The GCVS is made up of several intercommunicating parts:
1. The CS and its ventricular tributary veins
2. The anterior cardiac venous system
3. The superior interventricular septum veins
4. Left atrial veins
5. Mediastinal tributary veins to both atria
6. Right atrial veins
Vol. 25, No. 2, February 2013
Lesser Cardiac Venous System
In mammal’s hearts, there are multiple small, thin, vascular
connections between the coronary arteries and the heart chambers, made up of canals, lacunae, and sinusoids located in the
subendocardial layers of both the atrial and ventricular cavity
walls. This system has been described since 1928 by Wearn et
al11 and later confirmed by observations and descriptions of
other authors.12,13
Numerous orifices of small vessels belonging to the LCVS
are found, especially in the septal walls and the lateral wall of
the right ventricle, as well as in the left atria.14 The presence of
small venous vessel ostia has also been described in the surface
of papillary muscles. The vessels of the LCVS are classified into
four types, according to the descriptions of different authors:15,16
1. Sinusoidal vessels, which are the smallest veins (venules);
connect the intramural veins with subendocardial sinusoids and drain the internal layers of the atrium and the
ventricular myocardium.
2. Venoluminal vessels, which connect the intramural venous network with the atria or ventricles.
3. Arterio-sinusoidal vessels, which connect thin arteries or
arterioles with the sinusoidal spaces in the internal layers
of the atria and ventricles.
4. Arterio-luminal vessels, which connect small arteries or
arterioles with atria or ventricles.
Through microanatomy and histology techniques, using injected human heart specimens and electronic microscopy, it has
been shown that the vessels that make up this system are of a
highly variable form (canals, sinusoids, tree, etc), number, size, and
length (on average, 15 mm). They go in all directions, without orientation and achieve connections with veins from the middle layer.
Histologically, these vessels do not have a middle muscular layer.
They are made up of a layer of endothelial cells that are continuous
with the endothelium of the cardiac cavities.17
The vessels that make up the LCVS are able to collect a great
amount of venous blood and they supply sufficient nutrients
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Figure 2. Angiographic image of the coronary sinus (CS). Catheter located in the CS. Manual injection of contrast medium for retrograde filling.
(A) Right anterior oblique 10° projection. (B) Left anterior oblique 30°, Cranial 10° projection.
C
Figure 3. Angiographic image of the coronary sinus (CS) and its tributaries: postero-lateral branches and middle cardiac vein. Catheter located
in the CS. Manual injection of contrast medium through a balloon-catheter for retrograde filling to guide electrode placement for biventricular
pacing. Anteroposterior view.
from the ventricular cavities to the myocardium to be able to
maintain rhythmic contractions for long periods of time. They
are able to store close to 30% of the cardiac venous flow.18
Coronary Venous Sinus
The CS is a superficial vascular structure located in the sulcus between the left atrium and the left ventricle. It is defined
as the conduit of blood which is a continuation of the greater
cardiac vein, extending from the greater cardiac vein valve to
its ostium in the right atrium (Figure 3). The CS flows into
the right atrium through the Thebesian valve. Although it has
traditionally been considered simply a conduit of venous return
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to the right atrium, a close examination reveals that its structure
is similar to the other cardiac chambers, having endocardium,
myocardium, and a specific conduction system that is continuous with that of the right atrium. These findings suggest that
the CS may also play a role in the normal and abnormal electrical conduction of the heart.19
The CS is the most constant structure in the cardiac venous system. Although it has many variations in position,
form, length, and diameter, it has been described as being up
to 40 mm long in an 80 kg individual (in 75% of cases it is
between 30 and 50 mm long) and 10 mm in diameter.20 It is
cone shaped or cylindrical and its size has been equated to that
of the middle phalange of the fifth finger of a healthy adult
(Figure 2). In pathologic conditions, such as heart failure and
ventricular hypertrophy, the CS may grow several times its size.
It is found in the posterior portion of the coronary sulcus in the
diaphragmatic (posterior) wall of the heart. It stretches from
the left ventricular margin, from the left atrial oblique vein
(vein of Marshall) up to the orifice in the right atrium, in the
area known as the “crux of the heart.”21
The CS receives most of the ventricular epicardial veins.
The confluence of the GCVS and the CS occurs at a terminal
point delimited by the left atrial oblique vein. It then descends
toward the posterior wall. The atrial ostium of the CS is frequently oval shaped and provides a valve with a concave edge.
In some cases, this valve is absent (19% of specimens), and in
others it is completely round, septal, semilunar, or cribriform.
In rare cases, it is severely dilated or aneurysmic, resembling a
compact intrapericardial tumor.
Thebesian Venous System
The first vertebrates feed the myocardium by simply absorbing blood from the lumen of their ventricles. This simple
diffusion is the classic method of nutrition and waste elimination in inferior organisms that lack vascular systems.22 At the
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Myocardial Venous Drainage: From Anatomy to Clinical Use
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Figure 4. CT angiography images that show the relationship of the coronary sinus to the epicardial blood. (A) Cranial view that assesses the
relationship with the anterior descending artery. (B) Oblique view where
the circumflex artery is associated with the coronary sinus. (C) Lateral
view where the coronary sinus is seen in its greatest extent in the atrialventricular groove and its relation to the circumflex artery.
In 1951, Tori26 was the first to describe the retrograde injection of contrast media to the myocardium through the heart’s CS.
Since then, descriptions have been made of coronary venous retrograde perfusion preserving the myocardium during experimental
ischemic coronary occlusion and it has been used clinically for administering oxygenated blood to the ischemic myocardium during
unstable angina27,28 or high-risk percutaneous transluminal coronary angioplasty (PTCA),29-31 and in cardiac surgery,32 showing an
improvement in ischemia and reducing episodes of chest angina.
Retrograde percutaneous arterialization of coronary veins in
patients unsuited for conventional myocardial revascularization
has been previously described.33 The selective delivery of genes,
growth factors, and stem cells to the myocardium through the
coronary veins has shown higher success rates than intra-arterial
or systemic delivery, supporting this as a novel use of the heart’s
venous system.34-37 It has also been used by electrophysiologists as
an electrode insertion route for left ventricular stimulation in cardiac resynchronization therapy,38 ablation with radiofrequency
catheters, arrhythmia mapping,39 and defibrillation.40
beginning of the 17th century, Raymond Vieussens (16351713) and Adam Christian Thebesius (1686-1732) discovered
the vasa cordis minima, known today as the Thebesian veins.
These veins are part of the LCVS. Careful anatomic analyses
have identified three distinct forms of these veins.3,23,24 The first
type of venous drainage from the Thebesian veins consists of
the capillary bed toward the ventricular cavity.23 In the second
type, the arterioluminal vessels drain blood directly from the
arteries toward the ventricles without crossing the capillary
beds, thus having a greater diameter. In the third type, the venoluminal vessels form direct connections with the coronary
veins, carrying the blood from these vessels to the ventricular
cavities.25 Most Thebesian vessels in the ventricles appear to be
of a venoluminal nature.3 The presence of an extensive Thebesian venous network, which in a healthy state contains 5%10% of venous return, is an alternative route for myocardial venous drainage. It has been determined that the Thebesian veins
are able to carry out the majority of venous return in situations
where the epicardial coronary veins are compromised.
Coronary Venous System: An Alternative
Myocardial Access Route
The coronary venous system has been studied with great interest recently as an alternative route for accessing the myocardium. There are three conditions in which an understanding of the
venous system can lead to useful clinical interventions. First of
all, the use of percutaneous techniques for allowing retroinfusion
of oxygenated (arterialized) blood in the coronary veins of patients considered to be unsuited for conventional revascularization procedures. Second, the regional application of therapeutic
agents such as cardio-protective drugs, cells, or gene vectors. And
last, the use of the coronary venous system as an access route to
the myocardium for electrophysiology procedures.
Vol. 25, No. 2, February 2013
Access to the Coronary Venous System
Percutaneous cannulation of the CS and some tributary coronary veins, as well as the possible applications of this technology,
have been described for some time.41 Different catheter types have
been used to properly gain access to the coronary veins through
the CS. Access has been reported through the right and left subclavian veins, the right internal jugular vein, and the femoral veins.
Katritsis et al42 reported success in cannulation of the CS through
the femoral vein using a modified 6 Fr Judkins JL5 catheter. Other
authors report access to the CS with a left-type Kids Health catheter in 15 patients with an average cannulation time of 3.34 ± 1.9
minutes.43 Coronary complications of CS cannulation have been
reported in a small percentage, which include arrhythmia, dissection, and perforation with hemopericardium.44
Retrograde Venous Coronary Perfusion
The CS and its affluents provide an alternate access route
to the myocardium in the presence of total occlusions or severe
stenosis of the coronary arteries. The first studies by Pratt,45
Beck,31 and Batson and Bellet46 documented the possible benefit of reverse flow in the coronary venous system for oxygenation and nutrition of the myocardial cells. By perfusing the
CS, Pratt was able to maintain cardiac contractions for 90 minutes in a devascularized feline heart model. Gross et al47 reported an attempt to increase coronary perfusion while partially
occluding the CS in animals. These animals tolerated anterior
descendent artery ligation better than control animals that did
not have partical CS occlusion. The multiple descriptions that
rule out coronary venous system compromise due to atherosclerosis27 encourage even more research of the coronary venous
system as an alternative system for maintaining nutritional flow
to the myocardium in patients with severe involvement of arterial circulation. Prior to the advent of bypass surgery, surgeons
experimented with arterializations of the coronary venous system. Beck et al31 refined this procedure during the 1940s. In
an operation known as the Beck II procedure, they would first
obstruct the CS using ligation. After 10 days, during which
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ECHEVERRI, et al.
for PTCA. In the 1980s, retroperfusion of the CS was used as
a way to protect the myocardium during angioplasty in this
group of patients. The technique was able to reduce both anginal symptoms during PTCA as well as the time to appearance
of ischemia as seen in ST-segment changes following balloon
inflation.30 However, in spite of these results, the use of retroperfusion of the CS continues to be limited. The main reason for its underutilization seem to be that the retroperfusion
equipment has technical limitations and is slow to configure; in
addition, it is technically impossible in 10%-20% of patients.
Also, the degree of myocardial protection, although of some
benefit, was proven to be limited and the technique was only
tested in anterior descending artery interventions.
Local Drug Delivery
Numerous studies have researched the efficacy of retrograde
perfusion of pharmacologically active agents to the myocardium
through the coronary veins. In intact, non-ischemic myocardiums, the medication concentration following retroinfusion is
similar to that achieved when the medications are administered
intravenously (IV). However, in the context of myocardial ischemia, retroinfusion achieves higher levels of concentration of
the medication in the tissue than when it is administered IV,
with the advantage of having lower peak systemic concentrations and fewer systemic side effects.57-60 This increase in tissue
penetration is probably due to an improved low-pressure access
to the capillary bed and diminished washout of the drugs due
to the decreased anterograde blood flow. Thrombolytic agents,
when administered directly in the coronary veins, act faster,
improve functional recovery, and reduce the size of the infarct
compared with systemic administration.37
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the CS had fibrosed, an arterial or venous conduit was placed
between the aorta and the CS. The initial experimental work
on this procedure was carried out on dog animal models. This
revealed two important physiological characteristics: the CS
could tolerate arterial pressure for a long period of time, and
there was not a broad fistula effect following CS arterialization.
Beck’s focus was termed “global retroperfusion” as the method
for carrying oxygenated blood to the whole coronary venous
system. Beck perfected his experimental technique (Beck II
procedure), and in 1954, he and Leighninger32 reported a series
of 200 patients who had undergone this procedure. However,
they found that the permanent obstruction of coronary venous
drainage was associated with specific problems, including hemorrhage, fibrosis, and myocardial edema.
A second means of venous revascularization, the selective
method, in which blood flow is reversed only in precise ischemic areas caused by arterial disease, was proposed by Arealis.48
Using this method, only a small portion of venous drainage is
reversed, with the epicardial and Thebesian venous systems, and
other territories continue to function normally. Various groups
have perfected these procedures throughout the following years
with encouraging results.28,49,50 With the advent of bypass surgery, interest in this technique dwindled; ongoing studies were
abandoned and new studies on this topic were relegated.
The advent of synchronized diastolic coronary retroperfusion
allowed intermittent venous drainage of the myocardium, which
is produced during retrograde perfusion. This technique has been
shown to decrease pain episodes in patients with unstable angina51 and reduce complications in patients undergoing high-risk
PTCA.29,52,53 It is clear that with the new revascularization techniques
and the evolution of pharmacologic therapy generating an increased
life expectancy in patients with coronary disease, the number of patients considered poor candidates for myocardial revascularization
using conventional techniques is increasing and this has renewed interest in the techniques that use coronary veins to carry oxygenated
blood to ischemic myocardial zones. A novel percutaneous procedure for retrograde arterializations of the anterior coronary veins has
been developed and carried out recently in man.33,54 This technique
has been used in patients with anterior descending artery occlusion
in whom the anterior ventricular vein has been arterialized. The procedure was carried out using specially designed catheters which allow
passage of a 0.014˝ guide and subsequent release of a stent that connects the artery and the vein. However, according to the authors, the
procedure has been limited by technical problems.55
The percutaneous bypass between the ventricle and a coronary vein is being evaluated as a novel technique for patients
who are not suitable candidates for revascularization. The procedure consists in implanting a polytetrafluoroethylene-covered
stent directly between the left ventricular cavity and the superimposed coronary vein, in order to provide systolic flow of arterial blood in the coronary vein and also allow diastolic drainage
of the vein in the ventricular cavity. The procedure has proven
to be technically viable and able to maintain cardiac function in
the presence of an occluded coronary artery. Clinical trials are
currently under development.56
Patients with poor left ventricular function and large areas of ischemic myocardium are considered high-risk patients
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Delivery of Genes, Growth Factors and Stem Cells
The genomic and proteomic revolution continues advancing, and the underlying molecular biology of several cardiovascular pathologies is increasingly well understood. This understanding, in turn, leads to an increase in the number of possible
molecular therapies available. The success of these treatments
depends on many factors, among which is the ability to be delivered adequately to the target tissues. Some agents have shown
bioactivity when administered systemically. However, it is assumed that most agents are more effective and better tolerated
if they are delivered locally.
The delivery of genes to the heart has been attempted using viral and non-viral vectors. Adenovirus is the viral vector
that has proven most effective in vivo; however, adverse immune and inflammatory responses may limit its use. Direct
injection of vectors based on plasmids to the myocardium has
been reported, although the level of gene expression with this
method is relatively low.36 The delivery of genes to the myocardium by retrograde venous perfusion in a porcine model has been
reported34,35 and proved superior to percutaneous and surgical
gene transfer.61 Penta et al62 showed a plasmid gene delivery vector,
hDel-1, known to have angiogenic activity in angiogenesis trials
when it is administered to the myocardium through the coronary
veins. It was found in high concentrations in the myocardium, but
is absent or at a much lower concentration in peripheral tissues.
The Journal of Invasive Cardiology®
Myocardial Venous Drainage: From Anatomy to Clinical Use
in some patients, and for this reason, CS endo-epicardial ablation is an important step during radiofrequency ablation for
patients with persistent AF today.80
The ligament of Marshall as an anatomical structure is a
remnant of the left superior vena cava and contains nerve fibers
with significant electrical conduction properties, connected to
the CS muscular tissue in its proximal portion and with the left
pulmonary veins in its middle portion. The vein of Marshall
has been a focus point during ablation of paroxysmal AF in
young patients, as this structure is an important trigger of arrhythmic events in up to 20% of these cases.81
Knowledge of the exact anatomical location of the CS ostium is paramount during ablation of AV nodal re-entrant tachycardia (AVNRT), as it helps delineate the anatomical boundaries of the triangle of Koch, which is made up in its posterior
portion by the tendon of Todaro, anteriorly by the septal cusp
in the tricuspid ring and inferiorly by the CS ostium.82 The
middle portion of this anatomic triangle contains the compact
AV node. In patients with AVNRT, there are at least two (and
at times multiple) pathways with different conduction properties that constitute the necessary circuit for this re-entrant
arrhythmia (classically labeled as slow-fast for typical AVNRT
and fast-slow or slow-slow for atypical AVNRT). The slow
pathway, which is usually located at the base of this triangle, is
the preferred target of radiofrequency modulation or cryoablation for treating this arrhythmia, as the risk of complete heart
block using this approach is <1%.
Lastly, the coronary sinus provides direct access to the cardiac
venous system as a potential approach during mapping and ablation
of ventricular tachycardias originating from an epicardial substrate.
By placing electrode catheters into the coronary sinus, electrical
mapping of low-amplitude diastolic potentials and early local electrograms can guide successful VT ablation in areas of difficult endocardial access such as the mitral annulus (via the greater cardac vein)
or the left ventricular summit, at the junction between the greater
cardiac and the anterior interventricular veins.83-85
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Growth factors (GF) with angiogenic properties, such as fibroblast basic growth factor (FGF-2) and vascular endothelial
growth factor (VEGF), induce growth of collateral coronary
vessels.63 Various methods for introducing these GFs to the
myocardium have been studied, such as direct injection to the
myocardium and coronary artery infusion.64,65 Von Degenfeld
et al66 reported the selective and regulated use via venous coronary retroinfusion of FGF in a porcine model of chronic ischemia. The venous delivery of GF has been favorably compared
with intracoronary infusion and has also led to greater levels of
meshing of the tissue with FGF-2 and has improved coronary
perfusion through collateral vessels.
Recent studies have emphasized stem cell transplant as an
emerging treatment for patients in end-stage heart failure.67,68
The two main methods for delivering stem cells to the myocardium have been researched: these are direct (through intramyocardical injection)69 and intracoronary infusion.70 Both methods have proven to be effective. However, it has been shown
that cells injected directly into the heart to form small islets
may be isolated from native myocardium, and intracoronary
infusion may not allow the cells to reach the ischemic myocardium. Suzuki et al(37) reported a rat model of retrograde venous
perfusion of stem cells in the myocardium. This infusion route
has been proven to allow cellular diffusion to all layers of the
myocardium with minimal adverse effects seen during or following the retrograde infusion.
Coronary Venous System in Cardiac
Elecrophysiology
The knowledge of coronary venous anatomy is of vital importance for the practice of modern electrophysiology. The venous system has become a crucial access route for the invasive
management of pathologies, such as advanced cardiac failure,
atrial fibrillation, and some supraventricular and ventricular
tachycardias. The CS allows percutaneous endocardial access to
posterolateral veins that drain the left ventricle, through which
guides and catheters can be advanced for placing electrodes used
in cardiac resynchronization therapy through programmed biventricular stimulation in patients with advanced heart failure.
This improves their functional class and decreases ventricular dyssynchrony which, in turn, improves the effectiveness of
myocardial contractions, increases forward cardiac output and
decreases regurgitant mitral volume (Figure 3).40,71-74
The CS approach is also useful in managing atrioventricular (AV) re-entrant arrhythmias, being routinely used as an alternative approach in the ablation of left accessory pathways,
as the majority of these anomalous connections tend to have
epicardial fibers and insertions which on occasion cannot be
eliminated through conventional endocavitary ablation.75-77 In
some cases, AV re-entrant tachycardias that use the ligament of
Marshall as a re-entry mechanism have been successfully eliminated by catheter ablation through the CS and the vein of Marshall.78 In addition, some CS fibromuscular tissue bands have
electrical conducting properties, and cases of atypical atrial flutter have been described in patients following pulmonary vein
isolation.79 On occasion, these CS muscular fibers can be the
substrate that triggers and perpetuates atrial fibrillation (AF)
Vol. 25, No. 2, February 2013
Venous System in Valvular Interventions
With the growing interest in structural interventions and
the development of percutaneous techniques for the treatment
of valvular pathologies through percutaneous routes, the cardiac venous system, and especially the coronary sinus, is attractive
because it is a structure located parallel to the posterior portion
of the mitral ring and surrounding up to two thirds of the ring,
making it possible to implant devices via this route with the
capacity to shorten the length of the coronary sinus and in this
way carry out a valvular annuloplasty. Early animal studies have
shown that devices implanted through the coronary sinus can
reduce the circumference of the mitral ring in normal mitral
valve models or induced mitral insufficiency models in induced
dilated cardiopathy with a rapid pacemaker.86 In a generic
way, these devices seek to create a tension or constriction of
the sinus, which is transmitted to the mitral valvular apparatus
and especially to the valvular ring. Currently, there are initial
experiences in humans with the Cardiac Dimensions Carillon (Cardiac Dimensions), Edwards Monarc System (Edwards
Lifesciences), and the Viacor PTMA system (Viacor) devices.
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Conclusion
The knowledge of cardiac venous drainage, in spite of centuries of study, has been neglected. Only in the last decades has
interest been shown in the coronary veins as a possible myocardial access route for catheter interventions and delivery of
therapeutic agents. In spite of the early promise of retrograde
perfusion in patients undergoing high-risk PTCA, this technique is not routinely used today. However, retrograde arterialization of coronary veins is a new percutaneous treatment
with great potential for patients who “do not have the option”
of myocardial revascularization due to severe symptomatic
coronary disease. The use of coronary veins as a conduit for
therapies such as gene vectors and stem cells is garnering greater
attention and will play an important role in the development
of these treatments.
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The Cardiac Dimensions Carillon system consists of a
nitinol guide that has been molded to form a proximal and
a distal anchor; these are joined by bridge elements with the
ability to shorten the length of the coronary sinus.87 The
first studies in humans found a decrease in mitral valve insufficiency in at least one degree in all cases, improving left
ventricular function and decreasing ventricular diameter
and volume. Likewise, a symptomatic improvement was
achieved with a decrease in functional class and improvement after 6 minutes of continuous walking at 6-months
follow-up exam.88 The Edwards Monarc system is made up
of proximal and distal anchors formed by self-expanding
stents, and a bridge system that joins them.89 The distal
anchor is released in the anterior interventricular vein and
the proximal anchor near the coronary sinus ostium. Once
a large part of the mitral ring circumference is captured, the
bridge segment is tensed in order to shorten it. The initial
experience with this device showed a one or two degree reduction in insufficiency in most patients.90 However, the
EVOLUTION II study (Clinical Evaluation of the Edwards
Lifesciences Percutaneous Mitral Annuloplasty System for
the Treatment of Mitral Regurgitation) was suspended due
to patient inclusion difficulties. Lastly, the Viacor PTMA
system91 consists of a trilumen catheter that may be implanted through the subclavian, with different nitinol guides that
are advanced through the catheter lumen. Pressure is applied to the central portion of the posterior mitral ring, thus
shortening the distance between the septum and the distal
wall with a consequent shortening or constriction of the mitral ring.92 Initial studies showed a discrete decrease in the
degree of insufficiency in most included patients, which was
maintained throughout the first year of follow-up. However,
the company suspended the research line and inclusion of
new patients in the study.93
Although the devices are technically feasible to implant
in most patients, technical problems have been described
secondary to the anatomic variations of the coronary sinus, as well as material fatigue with device fracture, which
has been described with the three devices and is related
to the complex dynamics of compression and torsion that
the device undergoes during the cardiac cycle. Another
significant limitation is the compression of the circumflex
artery by the device. 94 Most devices that cause compression
of the circumflex artery present dramatic clinical manifestations during the procedure, forcing the removal of the
device and cancellation of the procedure. Evaluation with
multidetector scanning is very useful for detecting the anatomic relationship of the coronary sinus to the body of the
circumflex artery and the marginal branches in order to
decrease this complication. During the initial experience
with these devices, their implantation was only successfully accomplished in two-thirds of the cases; most cases
of failed implantation were due to anatomic variations of
the sinus that make it unfavorable, cannulation difficulties
with the guide catheter, or compression of the epicardial
arteries. Even so, the results obtained at this time foreshadow a promising future for this type of device.
104
The Journal of Invasive Cardiology®
Myocardial Venous Drainage: From Anatomy to Clinical Use
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