Classification of Coronary Lesions

Classification of Coronary Lesions

Understanding the risk of a procedure is the key to intelligent decision making. From the inception of angioplasty in 1977, the importance of lesion characteristics in determining technical success and the importance of lesion characteristics and clinical issues in predicting complications were recognized.
There are three possible outcomes of an intervention, not necessarily mutually exclusive: technical success, clinical success and an unsuccessful uncomplicated result.
Technical success reflects a focus only on the lesion itself, whereas clinical success requires an improved overall clinical result.
Technical success requires:
1. The ability to deliver the balloon or the device to the lesion.
2. The ability to adequately dilate the vessel or otherwise improve the lumen. (In the days of limited expectations success was defined as improvement of stenosis by 20% or to a diameter of the stenosis of less than 50% of the "normal" vessel. Now success is defined as a minimum stenosis less than 20%).
Clinical success requires technical success plus no peri-procedural complications leading to myocardial infarction, emergency coronary bypass and/or death.
To predict clinical success or complications especially death, clinical factors are as important as lesion characteristics.1 Simple procedures on high-risk patients are basically high risk procedures, since any possible unsatisfactory result, even a temporary occlusion could lead to clinical disaster.

In addition to identifying individual factors, which predict success, there is a need to combine and quantify this risk. Ideally, a simple score or lesion classification can be developed which reflects the difficulty of the procedure--the likelihood of success or complications. This permits normalization of the overall performance of the individual laboratory or operator according to the difficulty of the procedure. If a large database or registry is available, the lesion classification permits comparison of the individual operator and laboratory with the general experience. It also permits stratification of patients in large studies to account for or control for the complexity of the actual procedures. In practice, however, the goal of accurately predicting results has proven elusive. Unfortunately, success and complication rates present a moving target, moving so fast in some cases that before data can be published, the procedure has been improved. Thus the initial wide range of performance in lesions of differing complexity as predicted by the original 1988 classification (2) has been compressed at present due to improved technology and improved operator skills. In addition, developments in adjunctive pharmacology have further reduced the risks and improved success rates.
The ability to successfully treat complex lesions is a measure of the skill of the operator. The role played by operator volume in angioplasty performance was evaluated in an analysis from the SCAI registry from 1990-1992. (3) We found that success rates were similar for all operators, about 95%, regardless of yearly volume. The complication rate in the more complex lesions varied according to operator case volume, with as predicted the highest volume operators having the lowest complication rate in the complex C lesions (Figure 1). As expected, the lowest volume operators (<25 procedures per year) had the highest rate of complications (8%) but surprisingly, the second highest complication rate (6%) was suffered by the patients revascularized by the highest volume operators (>200 procedures per year) (Figure 2).

Figure 1

Figure 2
Analysis of the patient characteristics showed that the higher volume operators included a higher percentage of acute MIs in their procedures (11% vs. 5% for the < 100 per year operators). Of more interest, the percentage of C lesions tackled increased with increasing operator volume. Thus, the lesion classification system allowed normalization of the difficulty of the procedures and permitted an objective explanation for the higher complication rate in the higher volume operators. To a more limited extent, it provided an explanation for the relatively low complication rate in the lower volume operators as well. The more experienced the operator, the higher the percentage of the complicated (C) lesions. The less experienced operators did not tackle those more difficult lesions and thus were able to produce good results. (The very low volume operators not surprisingly did not choose difficult lesions but still did poorly). Thus, the individual operator seems to know his limitations, and select cases in which he would expect to be successful. The more experienced operator may choose to attempt more complex lesions, whereas the less experienced operator chooses more straightforward cases permitting him an acceptable success rate. Challenges to developing a classification: The relationship of features of the lesions to success rates presents a moving target since characteristics of an individual lesion, which limit successful intervention, are targeted by device manufacturers as challenges to overcome. Thus, balloons have become smaller to aid in crossing the tighter lesions, more pushable to negotiate tortuous vessels and simplify crossing tight coronary lesions, and stronger to permit use of higher pressures. Devices to remove atheromas or burr through calcified lesions have been developed and, of course, stents have been developed to protect against vessel collapse, dissection and acute occlusion. Better understanding of the immediate response of the hemopoietic system to coronary interventions and the critical role played by platelets and thrombus in acute coronary syndrome has led to the widespread introduction of platelet glycoprotein IIbIIIa receptor blockers, further reducing the likelihood of sudden catastrophic closure after the procedure. In addition, training programs have been formalized and operators are certified. Operators who have performed over 1000 procedures performed are now common. To get a historical perspective on the process of codifying the obstacles to successful angioplasty we can look at the report from the National Heart, Lung and Blood Institute Registry published in 1984.(4) Faxon and coworkers found that a circumflex artery location, calcium in the lesion and an initial severe stenosis were associated with reduction in success (defined as greater than or equal to 20% improvement). For example, a 99.9% lesion had a 59% likelihood of success in that registry and success was only 37% for total occlusions. Other factors judged important in 1984 were the experience of an operator and the geometry of the lesion. In 1983, a balloon could traverse the lesion in 75% of cases where it was attempted. Using these and other data, the ACC and AHA derived a lesion classification which they published in 1988 and has just been renewed unchanged (Figure 3) (2). This system grouped the individual criteria into three large categories. Initially it was expected that type A lesions (low-risk) would have a success rate of 80%. The type B lesions predicted to have 60-85% success and type C lesions, less than 60% successful. The characteristics of the lesion class differed by greater amounts of tortuosity, angulation of the segment, the length of the vessel, the presence of occlusions, issues with side branches and potential for protection. Figure 3 Ellis, et. al. evaluated these criteria in over 1000 lesions from the Multivessel Angioplasty Prognostic study.(5) They found that a bend stenosis, high-grade stenosis, chronic total lesions, bifurcation stenosis and male gender were all associated with reduced success rates. It is worth noting that the overall success occurred in 82.6% of patients, reflecting the state of the art in 1986 and 1987. They confirmed the usefulness of the ACC/AHA classification for success that ranged from 92% for A lesions to 60% for C lesions. They also introduced a modification adding a class B2 for patients who had more than one B criterion. Myler et al. also reviewed their own results to evaluate the ACC/AHA lesion classification.(6) Occlusion greater than three months, increasing lesion length and any thrombus were indicators of lower success rates. Diffuse disease, angulated lesions, bifurcation lesions that were unprotected, calcification and lesion severity of greater than 95% were associated with a higher complication rate. In particular, angioplasties of grafts were predictably unpredictable. This reflected the unpredictability of the final result plus the risk of "no reflow" related to distal embolization. They introduced the C-I and C-II lesions, the C-II lesion having two C characteristics. The ACC/AHA Lesion Classification system was then evaluated by Tan et al. in a rigorous study using data from Guys Hospital in London.(7) They performed a careful prospective evaluation of 729 patients using two independent observers unaware of the outcome at the time of the lesion review. These procedures performed from 1990 to 1993, had an overall success rate of 91% with major complications in 3.3%. In a careful comparison of the ACC/AHA Lesion subclasses, they found no differences between the class A and class B-I but there were significant differences between B-I and B-II. There were no differences in the success or complication rates between C-I and C-II classes. They also evaluated the success and failure rate of individual criteria within a class. They found that the impact of individual criteria varied considerably. For example, within the B class, success for lesions with eccentricity, minor tortuosity, irregular contour, ostial location, and protected bifurcation was all greater than 90% (success rate for A lesions without any of these features was 96%). On the other hand lesions 10-20 mm long with moderate angulation had success rates between 80-90% and lesions with calcium or thrombus or occlusions older than three months had success rates ranging from 70-80%. Individual characteristics therefore within the B or C classification demonstrated success rates of 57% for chronically occluded arteries to 84% for longer lesions or with moderate angulation. Based on this careful study we can say that the B and C lesion categories as originally proposed were quite heterogeneous encompassing both prognostically irrelevant and prognostically very important criteria. A key feature of a classification system is reproducibility. This subject was addressed by Angiographic Core Lab of the Bypass and the Angioplasty Investigation (BARI).(8; 9) Seventy angiograms were read a second time by an experienced investigator blinded to his first reading. The reproducibility of the individual features of the lesions was evaluated. Most of the features evaluated were those used to classify lesions in the ACC/AHA system (Figure 4). The Kappa statistic was used to evaluate reproducibility. A κ> .60 indicates good reproducibility whereas a κ< .40 is fair to poor. There was an excellent ability to separate C from A and B lesions but moderate reproducibility separating A from B from C and moderate reproducibility identifying angulation. There was fair to poor correlation for the other lesion characteristics that were evaluated.

Figure 4
Interobserver reproducibility of classifying lesions into the ACC/AHA ABC system was reported by Kleiman, Rodriguez and Raisner.(10) Two experienced operators each evaluated one hundred fifty lesions and compared their results. There was agreement in all three grades in only 61% of patients (κ= .24). The observers agreed in differentiating C from non-C in 81%. They did not include the B-I and B-II breakdown, so one might expect that if these were used, the agreement of all classes would be worse.
In spite of these issues, the ACC/AHA classification has been found useful. Zaachs et. al.(11; 12) evaluating patients angioplastied from 1994 to 1996 in a single center showed that success rates in the A, B-I and B-II classes were similar ranging from 96.3 to 95.1%, whereas the success rate with C lesions was 88.2%, (P < than .0001). They found that total occlusion and vessel tortuosity, both criteria for C classification, were predictive of procedure failure. The presence of thrombus, bifurcation lesions, inability to protect a major side branch and degenerated vein grafts were all associated with increased complications. The last three characteristics are used to define C lesions.
From the above one can make the following statements
1) The distinction between C and non-C lesions was reproducible at an acceptable level.
2) Patency was reproducible.
3) The reproducibility of many of the individual features of lesions, especially those that distinguish A from B lesions was fair to poor.
The data from the Society of Coronary Angiography and Interventions (SCAI) collected in 41071 single vessel interventions performed from 1993 to 6/1996 was used to evaluate the predictive ability of the ACC/AHA lesion classification system.(13) We were especially interested in evaluating the value of making distinctions between the A and B classes. In addition we were anxious to simplify the classification, especially since the more detailed distinctions were poorly reproducible at best. Figure 5 shows the success rates by ACC/AHA lesion class. There is a decreasing success rate with increasing lesion complexity. However, when the classes B and C were divided into the patent and occluded lesions in the class, it is clear that patency has a profound influence on success rates, and that also both B and C classes are quite heterogeneous with regard to risk (Figure 6). There is no difference between the A and the patent B lesions while the success rate of the patent C lesions is actually better than the occluded B. We then restructured the classification into four groups distinguishing only the C or non-C classification and whether or not the lesion was patent (Figure 7).

Figure 5


Figure 6

Figure 7
Thus while the ACC/AHA classification stratified success in lesions over a range of 97.2% to 84.1%, the SCAI classification graded patent success rate over the broader range from 96.8% to down to 75% for the occluded C lesions (Figure 8). In addition, the SCA&I system classified over 75% of patients into the low risk group which is consistent with expected results. With the AHA/ACC system only 31% of the patients were in the group A.

Figure 8
The ability of lesion class to predict complications especially the major complications of myocardial infarction, urgent coronary artery bypass grafting or hospital death was more limited. While it may seem on first viewing that the lesion classification can predict complications (Figure 9), on closer analysis several facts become clear. The more complex the lesion, the more acutely ill the patient (Figure 10). Since complications are related to patient acuity, especially the presence of an acute infarction, the apparent predictive ability of lesion classification on complications is spurious. In multivariate analysis, after entering clinical data the lesion class added little to the model predicting complications.

Figure 9

Figure 10
Dividing the patients into those with or without a myocardial infarction within 24 hours, one can see the different pattern of complications for each class of lesion for patients with or without an MI (Figure 11). In addition, segregation of lesions by vessel patency in the SCAI classification reveals a complicated interaction between patency and death and emergency bypass which is not seen with the ACC/AHA classification. In the non-infarcting patients, complications in class IV are less than with class II, In the ACC/AHA system these would both be lumped together as Class C lesions so this distinction would be lost. (Figure 12). This is due to the lower rate of bypass surgery in the Class IV patients and to a lesser extent, a lower rate of death. In fact if we looked at data for the unsuccessful procedures, grouped by SCAI vessel class, we can see that in the non-infarcting patient, SCAI class IV lesions have the lowest rate of complications, either death or emergency CABG (Figure 13).

Figure 11

Figure 12

Figure 13
For patients with a myocardial infarction, death is more likely in those with initially occluded vessels, either non-C or C (SCAI class III or IV) although the emergency CABG rate is highest in patients with patent C lesions. These findings are similar to the results presented by Harrell, where clinical factors were preeminent in predicting complications.(14) They found that only lesion category C or non-C had any predictive value.
Thus we must conclude that the simplified classification scheme, proposed by the Registry Committee of the SCAI13 (Figure 7) produces a better prediction of procedure success and as good a prediction of complications as the more complex ACC/AHA lesion classification system. In addition, the categories appear more homogeneous according to risk and complications.
In the past 4 to 5 years, an explosion of technology has occurred as industry has met the challenges defined by interventionalists. Balloon technology has progressed dramatically with smaller, low profile balloons; more pushable to access the lesion, more powerful to dilate stents and arteries without bursting. Atherectomy devices, to remove atheromas or break-up calcium have improved success in bifurcation lesions, and in calcified lesions. Stents, which prevent vascular collapse or occlusion and reduce the likelihood of restenosis, have been made more flexible and more easily delivered. Understanding the critical role of platelet activation, and reducing the need for antithrombotic therapy has simplified the post procedure management reducing periprocedural acute and sub-acute occlusion, and nearly eliminated vascular access complications. Effective treatment with platelet receptor IIa/IIIb inhibitors, has essentially neutralized the effect of clot. Other vexing problems seem ripe for solution. Distal embolization is being addressed by several embolic entrapment systems.
So the question must be asked: with all of this new technology, do lesion characteristics still have a role in risk stratification?
Unfortunately, problems remain with stent delivery. Tortuous and or calcified proximal vessels impede the advancement of stents and other stiff devices, such as cutting balloons.(11) Small vessels, bifurcation lesions and complete occlusions still remain as challenges. Complication rates have fallen dramatically. Analysis of those features which pose difficulties for stent deployment show that most are features of Class C lesions.(11) With the continued problems treating occluded lesions, it would seem that the SCAI classification based on distinctions between C and non-C, patent and occluded would still have some predictive value.
To evaluate the value of the lesion classification system in the more modern device era, these analyses were repeated in a more recent population of patients, in procedures performed from 06/96 to 06/99. Stents were placed in over 60% of these patients. Overall, success rates were higher, ranging from 97.9% to 83.2% for SCAI I to IV, and complications were also markedly reduced from, for example, a high of 4.8% for SCAI II in the earlier database to 1.3% for elective patients in SCAI Class II in the most recent database. Similar reductions were seen in all categories. Never the less, the lesion classification permitted a risk stratification, primarily for technical success.
Ellis et al reviewed the relationship between lesion characteristics and complications of the intervention. They found, after evaluating 27 candidate variables, that 9 were useful to predict complications. They found non-chronic total occlusion, degenerated vein graft, vein graft older than 10 years, lesion length more than 10mm, severe calcium, lesion irregularity, large filling defect, angulations greater than 45 degrees and eccentricity were independently correlated with adverse outcome. However, they did not utilize clinical factors, which have been shown to strongly correlate with anatomic features, especially non-chronic total occlusion (SCAI II). A number of authors have pointed out the importance of clinical factors to determining the complication rate, reducing the impact of lesion classification.(1; 14; 15)
In many respects, the lesion characteristics identified both by Ellis et al.(16) and Zaack et al.(11) are risk factors for stent placement. In fact, preliminary data from the ACC National Cardiovascular Data Registry (NCDR) suggest that lesion class, especially using the SCAI system, is an excellent predictor of stent usage. Ellis rightly points out the role of filling defects and non chronic occlusion. These features of the lesion are usually associated with acute coronary syndrome or infarction, and the risks of those procedures have been drastically reduced with the widespread use of IIb/IIIa platelet receptor blockers and now enoxaparin.
The present ACC/AHA classification as simplified by the SCAI Registry committee maintains value to predict angiographic success. It continues to define aspects of a lesion which pose difficulty to the operator even with new techniques and pharmacology. As success rates improve and complications become less frequent, it would seem appropriate to simplify lesion classification rather than make it more complex.
The use of lesion classification to predict complications is however limited by the overriding role played by the clinical situation. It is important therefore that some correction for the clinical state be used before using a lesion classification system to predict complications.
In summary, features of the lesion, which are captured in the SCAI classification system (Figure 7), can be utilized to control for anticipated outcomes. The present ACC/AHA classification has within it the features that remain important in determining the outcome of percutaneous coronary intervention procedures. The simplification embodied in the SCAI lesion classification system requires distinguishing only between C and non-C lesions and whether or not the vessel is occluded. It reduces the number of lesion specific criteria to seven. When tested in a large database, such as the SCAI Registry, this simplification predicts intervention success as well or better than the more complex ACC/AHA classification. The classification also makes a small contribution to predicting complications, but here, clinical state is most important.
REFERENCES
1. Block PB, Peterson EC, Krone R, Kesler K, Hannan E, O'Connor GT, Detre K: Identification of variables needed to risk adjust outcomes of coronary interventions: Evidence-based guidelines for efficient data collection. J Am Coll Cardiol 1998;32:275-282

2. Ryan TJ, Faxon DP, Gunnar RM, Kennedy JW, King SB, Loop FD, Peterson KL, Reeves TJ, Williams DO, Winters WLJ: Guidelines for percutaneous transluminal coronary angioplasty. A report of the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Subcommittee on Percutaneous Transluminal Coronary Angioplasty). Circulation 1988;78:486-502

3. Krone RJ, Vetrovec GW, Noto TJ, Johnson LW, and the Registry Committee(SCA&I).: Procedure complexity and outcome from the Registry of the Society for Cardiac Angiography and Interventions. Circulation 1993;88:I-300(Abstract)

4. Faxon DP, Kelsey SF, Ryan TJ, McCabe CH, Detre K: Determinants of successful percutaneous transluminal coronary angioplasty: Report for the National Heart, Lung, and Blood Institute Registry. Am Heart J 1984;108:1019-1023

5. Ellis SG, Vandormael MG, Cowley MJ, and the POSCH Group.: Coronary morphologic and clinical determinates of procedural outcome with angioplasty for multivessel coronary disease: implications for patient selection. Circulation 1990;82:1193-1202

6. Myler RK, Shaw C, Stertzer SH, Hecht HS, Ryan C, Rosenblum J, Cumberland DC, Murphy MC, Hansell HN, Hidalgo B: Lesion morphology and coronary angioplasty: current experience and analysis. J.Am.Coll.Cardiol. 1992;19:1641-1652

7. Tan K, Sulke N, Taub N, Sowton E: Clinical and lesion morphological determinants of coronary angioplasty success and complications: Current experience. J.Am.Coll.Cardiol. 1995;25:855-865

8. Rosen AD, Detre KM, Alderman EL, Stadius M, Sopko G, and the Bypass Angioplasty Revascularization Investigation (BARI) Study Group.: How reliable is the assessment of coronary angiography? Circulation 1993;88 (Suppl I):I 653(Abstract)

9. Botas J, Stadius ML, Bourassa MG, Rosen A, Schaff HV, Sopko G, Williams DO, Alderman EL, and the BARI Investigators.: Angiographic correlates of lesion relevance and suitability for Percutaneous Transluminal Coronary Angioplasty and Coronary Artery Bypass Grafting in the Bypass Angioplasty Revascularization Investigation Study (BARI). Am J Cardiol 1996;77:805-814

10. Kleiman NS, Rodriguez AR, Raizner AE: Interobserver variability in grading of coronary arterial narrowing using the American College of Cardiology/American Heart Association grading criteria. Am J Cardiol 1992;69:413-415

11. Zaacks SM, Allen JE, Calvin JE, Schaer GL, Palvas BW, Parrillo JE, Klein LW: Value of the American College of Cardiology/American Heart Association stenosis morphology classification for coronary interventions in the late 1990s. Am.J.Cardiol. 1998;82:43-49

12. Zaacks SM, Klein LW: The AHA/ACC task force criteria: what is its value in the device era? American Heart Association/American College of Cardiology [editorial; comment]. Cathet.Cardiovasc.Diagn. 1998;43:9-10

13. Krone RJ, Laskey WK, Johnson C, Kimmel SE, Klein LW, Weiner BH, Cosentino JJA, Johnson SA, Babb JD, for the Registry Committee of the Society for Cardiac Angiography and Interventions.: A simplified lesion classification for predicting success and complications of coronary angioplasty. Am J Cardiol 2000;85:1179-1184

14. Harrell L, Schunkert EH, Palacios IF: Risk predictors in patients scheduled for percutaneous coronary revascularization. Cathet Cardiovas Intervent 1999;48:253-260

15. Block PB: Doing it-Where's the risk? Cathet Cardiovas Intervent 2000;48:261-261

16. Ellis SG, Guetta V, Miller D, Whitlow PL, Topol EJ: Relation Between Lesion Characteristics and Risk With Percutaneous Intervention in the Stent and Glycoprotein IIb/IIIa Era
An Analysis of Results From 10,907 Lesions and Proposal for New Classification Scheme . Circulation 1999;100:1971-1976
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2nd Virtual Congress of Cardiology

Dr. Florencio Garófalo
Steering Committee
President Dr. Raúl Bretal
Scientific Committee
President Dr. Armando Pacher
Technical Committee - CETIFAC
President
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Coronary circulation
Coronary circulation is the circulation of blood in the blood vessels of the heart muscle (the myocardium). The vessels that deliver oxygen-rich blood to the myocardium are known as coronary arteries. The vessels that remove the deoxygenated blood from the heart muscle are known as coronary veins.



The coronary arteries that run on the surface of the heart are called epicardial coronary arteries. These arteries, when healthy, are capable of autoregulation to maintain coronary blood flow at levels appropriate to the needs of the heart muscle. These relatively narrow vessels are commonly affected by atherosclerosis and can become blocked, causing angina or a heart attack. (See also: circulatory system.) The coronary arteries that run deep within the myocardium are referred to as subendocardial.
The coronary arteries are classified as "end circulation", since they represent the only source of blood supply to the myocardium: there is very little redundant blood supply, which is why blockage of these vessels can be so critical.
The exact anatomy of the myocardial blood supply system varies considerably from person to person. A full evaluation of the coronary arteries requires cardiac catheterization or CT coronary angiography.
In general there are two main coronary arteries, the left and right.
Right coronary artery
The right coronary artery (RCA) originates above the right cusp of the aortic valve. It travels down the right atrioventricular groove, towards the crux of the heart.
At the origin of the RCA is the conus artery.
In addition to supplying blood to the right ventricle (RV), the RCA supplies 25% to 35% of the left ventricle (LV).





In 85% of patients, the RCA gives off the posterior descending artery (PDA). In the other 15% of cases, the PDA is given off by the left circumflex artery. The PDA supplies the inferior wall, ventricular septum, and the posteromedial papillary muscle.
The RCA also supplies the SA nodal artery in 60% of patients. The other 40% of the time, the SA nodal artery is supplied by the left circumflex artery.
The posterior interventricular artery (PIV) (or posterior descending artery (PDA)) is an artery running in the posterior interventricular sulcus to the apex of the heart where it meets with the anterior interventricular artery.
It is typically a branch of the right coronary artery (80%, known as right dominance). Alternately, the PIV can be a branch of the circumflex coronary artery (20%, known as left dominance) which itself is a branch of the left coronary artery.
Variants have been reported


Left coronary artery
It typically runs for 1 to 25 mm and then bifurcates into the anterior interventricular artery (also called left anterior descending (LAD)) artery and the left circumflex artery (LCX). Sometimes an additional artery arises at the bifurcation of the left main artery, forming a trifurcation; this extra artery is called the intermediate artery.[1]
The part that is between the aorta and the bifurcation only is known as the left main artery (LM), while the term 'LCA' might refer to just the left main, or to the left main and all its eventual branches.
A "first septal branch" is sometimes described.[2]







The left coronary artery, abbreviated LCA and also known as the left main coronary artery (often abbreviated LMCA), arises from the aorta above the left cusp of the aortic valve.
Both of these arteries originate from the beginning (root) of the aorta, immediately above the aortic valve. As discussed below, the left coronary artery originates from the left aortic sinus, while the right coronary artery originates from the right aortic sinus.
The "LAD", or left anterior descending artery (or anterior interventricular branch of the left coronary artery, or anterior descending branch) is an artery of the heart. It passes at first behind the pulmonary artery and then comes forward between that vessel and the left auricula to reach the anterior interventricular sulcus, along which it descends to the incisura apicis cordis.
In 78% of cases, it reaches the apex of the heart.
It supplies the anterolateral myocardium, apex, and interventricular septum. The LAD typically supplies 45-55% of the left ventricle (LV). The LAD gives off two types of branches: septals and diagonals.
• Septals originate from the LAD at 90 degrees to the surface of the heart, perforating and supplying the interventricular septum.
• Diagonals run along the surface of the heart and supply the lateral wall of the left ventricle and the anterolateral papillary muscle.

The "LCX", or left circumflex artery (or circumflex artery, or circumflex branch of the left coronary artery) is an artery of the heart. it follows the left part of the coronary sulcus, running first to the left and then to the right, reaching nearly as far as the posterior longitudinal sulcus. It doesn't mid region. The circumflex artery curves to the left around the heart within the coronary sulcus, giving rise to one or more diagonal or left marginal arteries (also called obtuse marginal branches (OM)) as it curves toward the posterior surface of the heart. It helps form the posterior leftventricular branch or posterolateral artery. The circumflex artery ends at the point where it joins to form to the posterior interventricular artery in ten percent of all cases, which lies in the posterior interventricular sulcus. In the other 90% of all cases the posterior interventricular artery comes out of the right coronary artery. The LCX supplies the posterolateral left ventricle and the anterolateral papillary muscle.
It also supplies the sinoatrial nodal artery in 38% of people.
It supplies 15-25% of the left ventricle in right-dominant systems. If the coronary anatomy is left-dominant, the LCX supplies 40-50% of the left ventricle.


Variations
Four percent of people have a third, the posterior coronary artery. In rare cases, a person will have one coronary artery that runs around the root of the aorta.
Occasionally, a coronary artery will exist as a double structure (i. e. there are two arteries, parallel to each other, where ordinarily there would be one).
[edit]Coronary artery dominance
The artery that supplies the posterior descending artery (PDA)[1] (a.k.a. posterior interventricular artery) determines the coronary dominance.[2]
• If the posterior descending artery (PDA) (a.k.a. posterior interventricular artery) is supplied by the right coronary artery (RCA), then the coronary circulation can be classified as "right-dominant".
• If the posterior descending artery (PDA) is supplied by the circumflex artery (CX), a branch of the left artery, then the coronary circulation can be classified as "left-dominant".
• If the posterior descending artery (PDA) is supplied by both the right coronary artery (RCA) and the circumflex artery, then the coronary circulation can be classified as "co-dominant".
Approximately 70% of the general population are right-dominant, 20% are co-dominant, and 10% are left-dominant.[2] A precise anatomic definition of dominance would be the artery which gives off supply to the AV node i.e. the AV nodal artery. Most of the times this is the Right Coronary Artery.
Blood supply of the papillary muscles
The papillary muscles tether the mitral valve (the valve between the left atrium and the left ventricle) and the tricuspid valve (the valve between the right atrium and the right ventricle) to the wall of the heart. If the papillary muscles are not functioning properly, the mitral valve may leak during contraction of the left ventricle. This causes some of the blood to travel "in reverse", from the left ventricle to the left atrium, instead of forward to the aorta and the rest of the body. This leaking of blood to the left atrium is known as mitral regurgitation. Similarly, the leaking of blood from the right ventricle through the tricuspid valve and into the right atrium can also occur, and this is described as tricuspid insufficiency or tricuspid regurgitation.
The anterolateral papillary muscle more frequently receives two blood supplies: left anterior descending (LAD) artery and the left circumflex artery (LCX).[3] It is therefore more frequently resistant to coronary ischemia (insufficiency of oxygen-rich blood). On the other hand, the posteromedial papillary muscle is usually supplied only by the PDA.[3] This makes the posteromedial papillary muscle significantly more susceptible to ischemia. The clinical significance of this is that a myocardial infarction involving the PDA is more likely to cause mitral regurgitation.
During contraction of the ventricular myocardium (systole), the subendocardial coronary vessels (the vessels that enter the myocardium) are compressed due to the high intraventricular pressures. However, the epicardial coronary vessels (the vessels that run along the outer surface of the heart) remain patent. Because of this, blood flow in the subendocardium stops. As a result most myocardial perfusion occurs during heart relaxation (diastole) when the subendocardial coronary vessels are patent and under low pressure. This contributes to the filling difficulties of the coronary arteries. Compression remains the same. Failure of oxygen delivery caused by a decrease in blood flow in front of increased oxygen demand of the heart results in tissue ischemia, a condition of oxygen debt. Brief ischemia is associated with intense chest pain, known as angina. Severe ischemia can cause the heart muscle to die from hypoxia, such as during a myocardial infarction. Chronic moderate ischemia causes contraction of the heart to weaken, known as myocardial hibernation.
In addition to metabolism, the coronary circulation possesses unique pharmacologic characteristics. Prominent among these is its reactivity to adrenergic stimulation. The majority of vasculature in the body constricts to norepinephrine, a sympathetic neurotransmitter the body uses to increase blood pressure. In the coronary circulation, norepinephrine elicits vasodilation, due to the predominance of beta-adrenergic receptors in the coronary circulation. Agonists of alpha-receptors, such as phenylephrine, elicit very little constriction in the coronary circulation
Anastomoses
When two arteries of the coronary circulation join, dual blood flow to a certain area of the myocardium occurs. These junctions are called anastomoses. If one coronary artery is obstructed by an atheroma, the second artery is still able to supply oxygenated blood to the myocardium. However this can only occur if the atheroma progresses slowly, giving the anastomoses a chance to proliferate. Under the most common configuration of coronary arteries, there exist two anastomoses on the posterior side of the heart. More superiorly, there is an anastomosis between the circumflex artery (a branch of the left coronary artery) and the right coronary artery. More inferiorly, there is an anastomosis between the anterior interventricular artery (a branch of the left coronary artery) and the posterior interventricular artery (a branch of the right coronary artery)

Cardiac Transplantation

Cardiac Transplantation
1. Clinical Advancesaa
A. 1960 - Surgical technique reported
B. 1967 - Successful human transplant
C. 1970 - Recipient selection criteria standardized
D. 1973 - Surveillance endocardial biopsy
E. 1977 - Distant donor heart procurement
F. 1980 - Cyclosporine A
Causes of Death
Transplant Volume
2. Etiology or End-Stage Heart Disease
Etiology Percentage
Ischemia 44.8
Cardiomyopathy 46.2
Valvular 3.5
Congenital 1.8
Rejection 2.1
Other 1.6
3. Recipient Criteria
A. Terminal heart disease
B. Reasonable physiological
C. No renal or hepatic dysfunction
D. No acute infections
E. No recurrent pulmonary infections
F. Psychosocial stability
G. No alcohol, tobacco or drug abuse
4. Contradictions
A. Fixed pulmonary vascular resistance
B. Peripheral vascular disease
C. Acute malignancy
D. COPD of chronic bronchitis
E. Morbid obesity
F. ABO incompatibility
5. Donor Criteria
A. Brain death declared
B. Age <45 (special exceptions) C. No re-existent heart disease D. Few CAD risk factors E. No untreated acute infections F. No systemic malignancy G. No cardiac trauma H. Normal ECG I. Normal echocardiogram J. Negative HIV and Hepatitis screen 6. Unique Features of Cardiac Recipient A. Prone to infection (opportunistic) B. Denervated heart physiology C. Rejection at any time- few symptoms 7. Immunosuppressive Therapy A. Cyclosporine A B. Adrenocortical steroids C. Azathioprine D. OKT3 E. Anti-thymocyte globulin (ATG) Immunosuppression 8. Rejection A. Endomyocardial biopsy B. Acute rejeciton 1) Hospital 2) Out-patient 9. Registry Database A. Fifteenth Report- 1998 B. Total Transplants Reported- 45,993 C. Total Centers Reported- 257 D. Survival 1) 1 year- 79% 2) Thereafter- 4% per year mortality Total Survival Survival by ERA Survival by Age Survival with Retransplant 10. Risk Factors(p value < 0.001) A. Previous cardiac transplant B. Ventricular support C. Mechanical support (VAD) D. Recipient < 5 years of age E. Recipient > 60 years of age
F. Donor > 40 years of age
G. Donor female
H. Ischemic time >3.5 hours
11. Causes of Death after Transplantation
A. Rejection
B. Infection
C. Technical
D. CNS
E. Malignancy
Cause of Death Post Transplant
F. After First year
1) Graft Atherosclerosis
2) Infection
3) Malignancy- Lymphoma
4) Rejection
12. Improved Survival
A. Cyclosporine
B. Lower chronic steroid dose
C. Earlier diagnosis of rejection
D. Better patient selection
E. Diagnosis of infection
F. New antimicrobial agents
G. Medical and surgical experience
13. Functional Status Following Heart Transplant
A. Post Transplant Functional Status
B. Post Transplant Work Status
C. Post Transplant Rehospitalization
EXTENDED OUTLINE
1. Candidate Selection
A. Most often from idiopathic dilated or ischemic cardiomyopathies
B. “End stage…failure to respond to maximal therapy”; need to identify those who are likely to have sudden death or progressing heart failure
C. Adequacy of therapy prior to evaluation is key
D. Some guidelines for selection of candidates:
1) EF < 20% 2) Peak O2 consumption (VO2) < 10cc/kg/min 2. Cardiac Donor A. Only 10-20% of brain dead patients with suitable hearts become donors; cardiac transplantation is currently limited by donor availability B. Initial screening done by a local organ procurement agency C. Hep C generally OK D. Level of inotropic support E. Cardiovascular risk factors F. Substance abuse G. Ideally, donor body weight 80-120% of recipient’s weight H. Age limits I. Intensive fluid management of the donor is important; often these people are hypovolemic from trauma or dibetes insipidus 3. Donor Cardiectomy A. Visualize/palpate the heart B. Divide the: 1) SVC 2) Left superior pulmonary vein 3) Incise IVC C. Clamp aorta D. Administer cardioplegia E. Avoid coronary sinus injury during liver procurement F. Divide aorta and pulmonary artery 4. Recipient Operation A. Open RA along the AV groove anteriorly B. Extend this incision to CS inferiorly and to the right atrial appendage posteriorly C. Aorta and main pulmonary artery are divide at the valve commissures D. Incise roof of the left atrium between the aorta and SVC E. Connect the atrial incisions and extend the incision to the left atrial appendage F. Incision is then extended along the AV groove posteriorly to the CS G. Check donor heart for PFO H. Donor pulmonary veins are connected to fashion a left atrial cuff I. Left atrial anastomosis is completed and a vent is placed J. Right atrial anastomosis is completed K. Great vessels are anastomosed; PA first L. Deair, pacing wires, choronotropic/inotropic support Herotopic Cardiac Transplantation 5. Posttransplant Concerns A. Immunosuppression 1) as detailed previously 2) use of tacrolimus as both maintenance therapy and rescue therapy; 3) Pittsburgh group has evidence to prove that there are fewer repeat episodes of rejection and it is an effective agent for refractory rejection B. Transvenous myocardial biopsy 1) IJ approach 2) 3-5 specimens 3) weekly for the first 4 weeks 4) grading system developed by Billingham C. Coronary graft vasculopathy D. Infection 1) bacterial are most common followed by viruses, fungi, and protozoans 2) viral most common between months 1-6 3) fungal most common between months 1-2 4) protozoal infections peaked months 3-6 5) in the first 6 weeks of transplant, CMV, Herpes, or bacterial are equally likely; >2yrs is usually bacterial pneumonia is the most common infection
6) CMV can be cultured from almost all recipients; consider active infection in anyone with fever, fatigue, lymphocytosis, elevated LFT’s , neutropenia, and thombocytopenia; 25% will develop invasive GI or pulmonary disease; most severe infections seen in those seronegative prior to operation; Gangcyclovir is used to treat, but its use should be prophylactic
7) HSV usually causes mucocutaneous infections
8) Ebstein-Barr infection seems to be related to the development of posttransplant proliferative disorder; most effective treatment appears to be reduction of immunosuppression
9) Candidiasis is the most common severe fungal infection seen posttransplant; aspergillosis also has a significant cause of death
10) PCP usually presents with fever, dry cough and dyspnea and may be slow to respond to therapy; TMP-SMX or pentamidine prophylaxis can usually prevent it; diagnosis is usually confirmed by methenamine silver stains on BAL fluid; rapid reduction in immunosuppression may exacerbate the process in the lung
6. Renal Failure
Most important side effect of cyclosporin—from afferent arteriolar vasoconstriction and direct tubular cell injury; is dose related to some extent and will improve with reduction in the Cyclosporin dose; oliguria occurs in the early form of renal failure—late nephrotoxicity is characterized by a slow rise in serum creatinine
7. Other
Hirsutism, tremor, gingival hyperplasia, gout, elevated cholesterol, hyperglycermia, osteoporosis, and abdominal surgical complications
8. Survival
A. One year: >80%
B. 3-5 years: 70%
C. 12 years: ~40%
D. Bridge to transplant > 90% survival
E. Risk factors: previous transplant, preoperative ventillator dependence, age <5 or >60 recipient)
F. Risk factors: age >40, female sex, ischemic time >3.5 hours (donor) most common causes of early death: cardiac complications (40%); rejection (19%); infection (16%).
G. Infection is the most significant factor in late deaths, accounting for 40%

Heart/Lung and Lung Transplantation
1. History
A. Alexis Carrel- 1907
B. Demikhov- 1940s
C. Lower/ Shumway- 1960s
D. Clinical heart/lung transplantation
1) Cooley- 1968
2) Lillehei- 1969
3) Barnhard- 1971
4) Modern- era- Reitz
E. 1963- first human lung transplant
F. 1983- Cooper- first successful lung transplant
G. 1985- Cooper / Patterson- double lung transplant
2. Donor Selection
A. Age <60 years B. No history of pulmonary disease C. Smoking history < 20 packs/ year D. Normal chest x-ray E. Adequate gas exchange F. Normal bronchoscopy G. Acceptable sputum gram stain H. Normal serology I. ABO compatibility J. Adequate size matching 3. Absolute Donor Criteria A. Adequate gas exchange 1) PO2 >300 on FiO2 1.0
2) PO2 >100 on FiO2 0.4
B. Absense of significant infiltrates
C. Normal serology
D. ABO compatibility
4. Indications of Thoracic Transplantation
A. Single lung transplant
1) Pulmonary fibrosis
2) Emphysema
B. Primary pulmonary hypertension
C. Double lung transplants
1) Septic lung disease
2) Cystic fibrosis
3) Bronchiectasis
D. Emphysema
1) Primary pulmonary hypertension
E. Heart / Lung transplant
1) Irreversible disease of both heart and lung
5. Recipient Selection
A. Age <65 B. Other disease processes C. Previous surgery D. Steroids E. Smoking F. Nutrition G. Ventilator dependence H. Timing of transplant I. Psychosocial factors 6. Lung Preservation for Transplantation A. Hypothermia B. Lung inflation C. Pulmonary artery vasodilation- PGE1 D. Pulmonary artery flush- solutions include: 1) Modified eurocollins solution 2) Belzer's (Wisconsin) solution 3) Low potassium Dextran E. Low potassium, colloids, free radical scavengers 7. Early Complications of Lung Transplantation A. Reperfusion pulmonary edema B. Primary graft failure C. Hemorrhage D. Bronchial dehiscence E. Non-infectious pleural space problems 8. Infection in Lung Transplantation A. Transplanted organ exposed to external environment B. Target organ for CMV C. Bacterial, viral (CMV), fungal Protozoan (PCP) D. Infection increases expression of 1) HLA antigens 2) Adhesion molecules (ICAM-1) E. Can trigger rejection F. Transbronchial biopsy / bronchoalveolar lavage to differentiate 9. Rejection in Lung Transplantation A. Routine screening B. Lung allografts more antigenic and more vulnerable to rejection C. Symptoms: malaise, shortness of breath, lung infiltrate D. Differentiating infection from rejection difficult E. Transbronchial biopsy, bronchoalveolar lavage useful F. Serial daily spirometry (FEV1) 10. Bronchiolitis Obliterans A. Primary factor limiting long-term survival B. Exact etiology unknown (chronic rejection/infection) C. Most important cause of mortality and morbidity after lung transplantation D. Affects 50% of long-term survivors E. 50% will respond to enhanced immunosuppression F. The remainder will have progressive deterioration of lung function 11. Pediatric Lung Transplantation A. Higher incidence of bypass B. May be more vulnerable to bronchiolitis obliterans C. Immune advantage has not been clearly documented in pediatric population 12. Survival after Lung Transplantation By Diagnosis Diagnosis 30 Days 1 Year Emphysema (SL) 93% 78% A1A (SL) 90% 75% Cystic fibrosis (BL) 90% 70% Pulmonary fibrosis (SL) 82% 65% Pulmonary htn. (BL) 80% 75% By Transplant Transplant 1 Year 5 Years Single (SL) 70% 40% Bilateral (BL) 70% 48% EXTENDED OUTLINE 1. Introduction A. 1963-Hardy @ U Mississippi 1st human lung transplant à 18d survival B. 1963-83 - 44 lung transplants w/o success [bronchial anastomosis/MOF] C. 1983 - Toronto Lung Transplant Group @ 6-yr survival 2. End-Stage lung disease A. Obstructive lung disease 1) Chronic elevation in airway resistance a) Decreased exp flow rates (FEV1, FVC, FEV1/FVC) b) Air trapping ( TLC and FRC) 2) Prognostic factors = age, degree of airway obstruction (FEV1) 3) COPD 4) Alpha-1 antitrypsin deficiency emphysema a) Lack protection against neutrophil elastase in distal airways b) Severe bullous emphysema by 4th or 5th decade B. Cystic fibrosis (CF) (1/2,000 live births) 1) Most common end-stage obstructive disease 1st-3rd decades 2) Thick secretions, poor ciliary fxn => mucus plugging, pulm sepsis
C. Restrictive lung disease - idiopathic pulmonary fibrosis (IPF)
1) Decreased Lung volumes and exp flow
2) Decreased diffusing capacity
D. Pulmonary hypertension
1) Primary pulmonary hypertension (PPH):Mortality correlates w/CVP >10mmHg, PA(mean) >60mmHg, CI<2L/min 2) Eisenmenger’s syndrome:Ca-channel blockers may [increase or decrease???] PA pressures E. Others: sarcoidosis, chemo/RT-induced fibrosis, lymphangiomatosis 3. Recipient selection A. Mean waiting time 9-12 mo. (Wash U) 13.5 mo. (US) 4. Preoperative evaluation and management of recipients A. All pts enrolled in cardiopulmonary rehab 5. Choice of procedure A. Obstructive lung disease 1) Early single lung transplant (SLT)àhyperinflating native lung, crowding, V/Q mismatch a) Oversizing donor lung b) Proper preservation technique 2) SLT for: >55yo, high risk), prior surgery, asymmetric dz
3) Bilateral lung transplant (BLT) for: younger,bilat dz,small donor
B. CF (and other septic lung disease)=> BLT due to infection risk in native lung
C. IPF
1) SLT theoretically ideal- decrease compliance and PA pressures in native lung favor allograft ventilation and perfusion
2) BLT for large individual, especially with nl lung volumes
D. PPH - Ht-lung transplant, traditionally
1) SLT has been successful
a) Post-op management difficult, nearly all pulm flow to allograft
b) Late graft problem=severe V/Q mismatch
2) BLT may provide better long-term result
6. Timing of transplantation
A. Pts w/life expectancy 12-24 mo
B. ~30% will receive transplant w/in 1 year
C. Risk of dying on the waiting list:PPH, IPF, CF >>> COPD
7. Other criteria
A. Age (not absolute): BLT=55, SLT=65
B. Ventilatory support- no longer an absolute contraindication (already listed)
C. Corticosteroid therapy - data suggest:
1) low-dose prednisone does not airway complications
2) low-dose steroids may allograft bronchial circulation
D. Prior surgery - no longer a contraindication, in general
7. Criteria for donor lung suitability
A. 20-25% of multiple organ donors have suitable lungs
B. Size - TLC, VC estimated by height/weight - oversize 20% for SLT
C. Donor lung scarcity
1) Use “marginal” lungs
2) Single lung assessment (2-lumen ETT, PA clamping)
3) Living related donor (for pediatric CF patients)
Technique of Lung Preservation and Extraction
1. Lung preservation
A. Prostaglandin E-1 before inflow occlusion (vasodilatation + other benefits)
B. PA flush w/3L cold Euro-collins
C. Extraction of lungs semi-inflated w/100% O2 (grafts use it)
D. Transport under hypothermia (0-1°C)
E. Topical cooling during implantation
2. Donor lung extraction
A. Median sternotomy, dissection
1) Isolate SVC and IVC
2) Separate aorta and PA-Cardiopleg. cannula in aorta, cannulate distal PA
3) Incise posterior pericardium, exposing distal trachea
B. Graft flushing
1) Bolus PGE-1 (500 mg)
2) Inflow occlusion (ligate SVC, clamp IVC)
3) Vent R heart - transect IVC
4) X-C aorta, administer cardioplegia
5) Amputate tip of LA appendage, start lung flush
6) Flood chest w/ iced saline, ventilate w/100% O2
C. Extract heart
1) Transect cavae and aorta
2) LA incision is last, leaving a cuff of atrium
D. Extract lungs
1) Divide trachea between two firings of TA-30
2) (Divide esophagus superiorly and inferiorly)
3) Transect descending thoracic aorta
4) Transport on ice
Lung Transplantation Procedure
1. Anesthetic considerations
A. PA catheter
B. Left-sided 2-lumen ETT
C. Initial bronchoscopy and aspiration for CF patients
D. Avoid “pulmonary tamponade”
E. CPB for:
1) Hemodynamic instability
2) Pulmonary vascular dz
3) Poor allograft function in BLT
2. Technique
A. Incision
1) SLT-posterolateral thoracotomy
2) BLT- bilateral transverse thoracosternotomy (“clamshell”) {5th IC space for COPD, 4th for CF}
B. Choice of side - avoid surgery, remove better lung - in BLT, worse lung transplanted 1st
C. R/O PFO in PPH-intra-op TEE
D. In SLT, CPB is selective - trial of PA clamping
3. Lung implantation
A. Divide 1st PA branch between ligatures, the staple PA trunk
B. Mobilize both pulmonary veins (PV) intrapericardially
C. Transect bronchus-R=just proximal to RUL takeoff, L=1-2 rings above bifurcation- hemostasis
D. Topical cooling - iced gauze around graft
E. Brocnchial anastomosis
1) Continuous 4-0 mono-absorbable for membranous
2) Telescope cartilaginous arches figure-of-8 interrupted sutures
3) Ometopexy no longer used
F. PA anastomosis - 5-0 mono-non
G. LA anastomosis - 4-0 mono-non
H. De-air
1) Antegrade (release PA clamp)
2) Retrograde (release LA clamp)
I. Bronchoscopy
4. Post-operative Management
A. ICU post-op - quantitative perfusion scan
B. Pain control - epidural
C. Ventilator
1) SLT: COPD=no PEEP, PPH=10cm PEEP x 36h
2) Weaning - PPH=sedated, paralyzed x 36h, others=early wean
D. Postural drainage (lat x 24h), chest PT
E. Hemodynamics: dopamine for diuresis, PGE-1
F. Bronchoscopy - OR, POD1, pre-extubation, and prn
G. Infection
1) Abx prophylaxis: CF - per recipient cultures; others, per donor, or ancef x 3-4d
2) HSV prophylaxis: acyclovir 200mg BID for ³ 2 yr
3) PCP:Septra-DS - one bid q M-W-F
4) Candida: nystatin
5) CMV
a) Attempt to match, avoid CMV neg recip/CMV pos donor
b) Prophylaxis=gancyclovir
H. Immunosuppression
1) Triple regimen: cyclosporine, azathioprine, corticosteroids
2) Antithymocyte globulin (ATGAM) x 8 days
5. Follow-up strategies
A. Clinical f/u - remain in town x 3 months
B. PFTs - primarily FEV1 - Monthly in 1st year
C. CXR - schedule similar to PFT’s + prn
D. Bronchoscopy (FOB) with transbrochial bx (TBLB)
1) 3-4wk post-op, 3mo, 6mo, 1yr, then annually
2) Direct TBLB to areas w/infiltrates
E. Open lung bx-when TBLB inconclusive in face of clinical, physiologic deterioration
6. Problems (clinical-pathologic entities encountered in the lung transplant recipient)
A. Acute rejection -more common than other solid-organ allografts
1) Incidence unknown - “virtually all” in 1st 3-4wks post-tx
2) From 1st 3-5 days post-op to years later
3) Clinical manifestation variable-malaise, mild dyspnea, fever, decreasedFEV1, decreased PO2
4) Dx:FOB, TBLB => 84% sens, 100% spec (Ht-lung tx)
5) Tx: High-dose steroids, maintenance prednisone, ATGAM or OKT3 for refractory episodes
B. CMV infection
1) May mimic rejection
2) Dx by TBLB
3) Tx w/gancyclovir (documented infection)
C. Chronic rejection/Bronchiolitis Obliterans syndrome (BOS)
1) Inflammatory disorder of the small airways-histologically, dense fibrosis and scar obliterating bronchial wall and lumen
2) Prevalence as high as 50%
3) Dry or productive cough, dyspnea refractory to bronchodilators
4) Airflow obstruction with progressive ¯ in FEV1
5) Tx: Immunosuppression (empiric)-most pts will progress
D. Bronchial anastomotic complications
1) Usually result from ischemia which =>
a) Air leak or mediastinal collection (early)
b) Stenosis or malacia (late)
2) New dyspnea, stridor or wheeze
3) W/U=CXR, FOB, chest CT
4) Tx:
a) Early (dehiscence) = drainage and conservative measures
b) Late (stricture or malacia) - stent
7. Results
A. Survival
1) 92% hospital survival
2) 70% 1-yr, 43% 5-yr
3) Small benefit of BLT vs SLT (not significant)
B. Functional results
1) FEV1, ABG, 6-minute walk improved
2) FEV1, PaO2, significantly better after BLT vs SLT
3) BLT associated w/ higher complication rate
C. Pulmonary vascular dz
1) Decreased PAS, CVP, PVRI
2) NYHA class III-IV => I-II

Cardiomyopathy / Cardiac Transplant Donor & Recipient Selection
1. Cardiomyopathy definition
A. Any myocardial disease process that leads to clinically significant myocardial dysfunction
2. Cardiomyopathy classification
A. Dilated cardiomyopathy
B. Hypertrophic cardiomyopathy
C. Restrictive cardiomyopathy
D. Arrhythmogenic right ventricular dysplasia
E. Dilated, characterized by dilation and impaired contraction of left or both ventricles
1) Idiopathic
2) Familial/genetic
3) Viral and/or immune
4) Alcoholic/toxic
5) Presentation with heart failure, often progressive, arrhythmias, thromboembolism, and sudden death
F. Hypertrophic, characterized by left and/or right ventricular hypertrophy
1) Usually asymmetric with normal or reduced LV volume
2) Systolic gradient common
3) Familial disease with predominantly autosomal dominant inheritance
4) Myocyte hypertrophy and disarray surrounding areas of increased loose connective tissue
5) Arrhythmias and premature sudden death are common
G. Restrictive, characterized by restrictive filling and reduced diastolic volume of either or both ventricles with normal or near-normal systolic function and wall thickness
1) Idiopathic
2) Associated with other disease (amyloidosis; endomyocardial disease with or without eosinophilia
H. Arrhythmogenic right ventricular dysplasia, characterized by progressive fibrofatty replacement of right ventricular myocardium, initially with typical regional and later global right and some left ventricular involvement with relative sparing of the septum
1) Familial disease common, autosomal dominant inheritance and incomplete penetrance
2) Presentation with arrhythmias and sudden death is common, particularly in the young
3. Specific cardiomyopathies: heart muscle diseases that are associated with specific cardiac or systemic disorders
A. Ischemic
B. Valvular
C. Hypertensive
D. Inflammatory (e.g., myocarditis, Chagas' disease, HIV, etc.)
E. Metabolic (e.g., thyrotoxicosis, hypothyroidism, storage diseases, etc.)
F. General system disease (e.g., SLE, sarcoidosis, etc.)
G. Muscular dystrophies (e.g., Duchenne, Becker-type, etc.)
H. Neuromuscular disorders (e.g., Friedreich's ataxia)
I. Sensitivity and toxic reactions (e.g., anthracyclines, irradiation, alcohol)
J. Peripartal
4. Prognosis
Factor Possibly Predictive Not Predictive
Factor Predictive Possibly Predictive Not Predictive
Clinical Symptoms Acoholism, Peripartum, Family History Age, Duration, Viral Illness
Hemodynamic LVEF, CI LV size, LAP, RAP Viral Illness
Dysrhythmia IVCD, Complex ectopy AV block Simple ectopy
Histologic Myofibril volume
Neuroendocrine PI, NE, ANF, Serum Na
Cumulative Mortality
Probability of Death
Probability of Survival
5. Pharmacological Treatment of Heart Failure
A. Digoxin*
B. Diuretics
C. Afterload Reduction
D. Isosorbine dinitrate/hydralazine**
E. Angiotensin Converting Enzyme Inhibitors
F. Enalapril**
G. Captoril**
H. Lisinopril
I. Angiotensin II Receptor Inhibitors
1) Losartan
J. Calcium Channel Blockers
1) Amlodipine
6. Beta Blockers
A. Carvedilol**
B. Metoprolol*
C. Inotropic Agents
D. Beta Agonists
1) Dopamine
2) Dobutamine
E. Phosphodiesterase Inhibitors
1) Amrinone
2) Milrinone
F. Anticoagulation
1) *Decreases risk of hospitalization or decompensation
2) **Decreases mortality
7. Pharmacologic Treatment of Heart Failure
Improves Survival Decreases Hospitalization Decreases Survival
Enalapril Digoxin Dobutamine
Captropril Metoprolol Milrinone
Isosorbide dinitrate Vesnarinone
Carvedilol
8. Recipient Selection Process
A. Inclusion criteria
B. Exclusion criteria
C. Ongoing re-evaluation process
9. Inclusion Criteria
A. Absence of reversible or surgically amenable heart disease
B. NYHA Class III - IV symptoms despite optimal medical management
C. Maximal oxygen consumption < 14 ml/kg/minute D. Estimated 1 year survival without transplant < 50% 10. Insufficient Indications for Cardiac Transplantation A. Ejection fraction < 20% B. History of NYHA Class III - IV symptoms C. Low maximal oxygen consumption 11. Candidate exclusion criteria Criteria High Risk Moderate Risk Pulmonary Hypertension PVR > 8 Wood Units, unresponsive to nitroprusside X
PVR > 8 Wood Units, decreasing in response to nitroprusside, but not below 3 Wood Units X
Pulmonary artery systolic pressure > 70 mmHg despite nitroprusside X
Transpulmonary gradient > 15-20 mmHg (mean PAP - PCWP) X
Infection - active, untreated X
Irreversible hepatic disease X
Irreversible renal disease X
Irreversible pulmonary disease
FEV1 < 1 L X FEV1 < 1.5 L X Recent pulmonary infarction X Age > 65 years X
Diabetes mellitus, Type 1, with significant end-organ damage X
Cerebrovascular disease
Symptomatic X
Asymptomatic X
Peripheral vascular disease
Symptomatic X
Peptic ulcer disease
Active bleeding X
Diverticulitis, recent X
Chronic Active Hepatitis X
HIV positive X
Malignancy, recent X
Malignancy, remote X
Psychiatric disease
Acute, unresolved X
Recent, resolved on treatment X
Substance abuse
Active, unresolved X
Recent,resolved X
12. Panel Reactive Antibody (PRA) Screen
A. AKA: HLA antibody or white blood cell antibody screen
B. Technique: Recipient sera placed in 40-60 wells containing lymphocytes with a wide variety of HLA antigens
C. Use: Determine presence of preformed antibodies
D. If > 10%: Prospective crossmatch
13. Management of Transplant Candidate While Waiting
A. Close follow-up
B. Low threshold for hospitalization
1) IV diuretics
2) Inotropic support
3) Mechanical assistance
C. Ongoing re-evaluation of candidacy
14. Ongoing Re-evaluation for Candidacy
A. Periodic assessment for degree of illness (VO2, EF, right heart pressures)
B. Periodic assessment of acceptability (development of a new or worsening of a pre-existing illness)
C. Periodic PRA determinations
15. Conditions Which Generally Preclude the Use of a Donor Heart
A. HIV positivity
B. Significant ventricular arrhythmia
C. Echocardiographic abnormalities
D. Significant global hypokinesis
E. Significant valvular abnormality
F. Significant coronary disease by arteriography or documented previous myocardial infarct
G. Any acute malignancy, except primary brain cancer
H. Inadequately treated systemic infection
I. HbsAG positive, unless recipient is also positive
J. Hepatitis C positivity, unless recipient is also positive
K. Death from carbon monoxide poisoning, with carboxyhemoglobin level > 20%
L. Significant cardiac contusion
M. Severe left ventricular hypertrophy by echo
N. History of intravenous drug use
16. Donor-recipient Matching
A. Size: Greater than 80% of recipient body weight
B. Blood type: Identical or compatible
C. HLA-matching: Generally not done
Transplant Immunology
Allograft Rejection
Th Cell Events
B & T Cell-Mediated Death
1. Phases of Immunosuppression
A. Early rejection prophylaxis
B. Maintenance rejection prophylaxis
C. Treatment of established rejection
2. Mechanism of Action of Immunosuppressive Agents
A. Inhibitors of Interleukin -2
B. Production
1) Cyclosporine A
2) Tacrolimus
C. Action
1) Rapamycin (Sirolimus)
2) SDZ RAD
3) Interleukin-2 Receptor Blockers
D. Daclizumab
E. Basiliximab
F. Inhibitors of purine or pyrimidine biosynthesis
G. Purine
1) Azathioprine
2) Methotrexate
3) Mycophenolate mofetil
4) Mizoribine (bredinin)
H. Pyrimidine
1) Brequinar sodium
2) Leflunomide
I. Both purine and pyrimidine
1) Cyclophosphamide
J. Opsonization of lymphocytes
1) Murine monoclonal anti-CD-3 antibody (OKT3)
2) Polyclonal antibodies (horse, rabbit)
I. Multiple mechanisms or not clearly defined mechanisms
1) Adrenocorticosteroids
2) 15-Deoxyspergualin
3. Murine Monoclonal CD-3 Antibody (OKT3)
A. Identification: IgG2a Murine Immunoglobulin
B. Mechanism: Inhibits signal transduction of antigen recognition, opsonizes CD-3 lymphocytes
C. Dose/route: 5-10 mg/day, IV
D. Side effects: First dose reactions, HAMA formation
E. Interactions: None
F. Use: Early rejection prophylaxis, treatment of rejection
G. Monitoring: CD-3 Counts, OKT3 levels
Total Lymphocytes
4. Polyclonal Antibodies
A. Identification: Horse (ATGAM) or rabbit (Thymoglobulin) immunoglobulin
B. Mechanism: RES-mediated removal of opsonized cells
C. Dose/route: ATGAM 10-20 mg/kg/day IV; Thymoglobulin 1.5mg/kg IV
D. Side effects: Leukopenia, thrombocytopenia, fever, arthralgias, serum sickness
E. Interactions: None
F. Use: Early rejection prophylaxis, treatment of rejection
G. Monitoring: CD-2 counts
5. Cyclosporine
A. Identification: Metabolite of tolypocladium inflatum gams
B. Mechanism: Inhibits m-RNA transcription of interleukin-2
C. Dose/route: 3-6 mg/kg/day orally; IV:Oral = 1:3
D. Side effects: Nephrotoxicity, hypertension, tremor, headache/paresthesias, hirsutism, gingival hyperplasia
E. Interactions: Increase clearance of cyclosporine
1) Rifampin
2) Isoniazid
3) Phenytoin
4) Phenobarbital
F. Decrease clearance of cyclosporine
1) Erythromycin
2) Ketoconazole
3) Diltiazem
4) Verapamil
5) Nicardipine
6) Cimetidine
7) Use: Maintenance immunosuppression
8) Monitoring: Blood or serum level determination
Cyclosporine Formulations
1. Sandimmune Liquid Liquid & Capsules
2. Neoral (microemulsion) Liquid Liquid & Capsules
3. Sang CYA (microemulsion) Liquid Liquid
6. Tacrolimus (FK-506)
A. Identification: Fermentation product of Streptomyces tsukubaenis
B. Mechanism: Inhibits mRNA transcription of interleukin-2
C. Dose/route: 0.05 - 0.075 mg/kg orally q 12 hours 0.03 mg/kg intravenously q 24 hours
D. Side-effects:
1) Nephrotoxicity
2) Hyperglycemia
3) Neurotoxicity
4) Hypertension
E. Interactions: Believed similar to cyclosporine
F. Use: Maintenance immunosuppression
G. Monitoring: Blood level determination
7. Azathioprine
A. Identification: Precursor to 6 mercaptopurine
B. Mechanism: Disrupts normal purine incorporation into ribonucleic acids
C. Dose/route: 1 - 4 mg/kg/day; IV:Oral = 1:1
D. Side effects: Hematologic, pancreatitis, cholestatic jaundice, hepatitis, interstitial pneumonitis
E. Interactions: Increased levels with allopurinol
F. Use: Maintenance immunosuppression
G. Monitoring: White blood cell count
8. Mycophenolate Mofetil (RS-61443)
A. Identification: Morpholinoethylester of mycophenolic acid, a fermentation product ofPenicillium species
B. Mechanism: Inhibits inosine monophostate dehydrogenase in the de novo pathway of guanine nucleotide biosynthesis
C. Dose/route: 1,000 - 1,500 mg orally q 12 hours
D. Side-effects: Leukopenia, Nausea, vomiting, diarrhea
E. Interactions: Probably with acyclovir
F. Use: Maintenance immunosuppression
G. Monitoring: None
9. Corticosteroids (Prednisone, hydrocortisone, methylprednisolone)
A. Mechanism:
1) Inhibit transcription of IL-1 and IL-6 encoding m-RNA in macrophages
2) Block antigen recognition, decrease IL-1 AND IL-6 driven effects
3) Redistribution of lymphocytes
B. Dose/route: Prednisone 1 mg = hydrocortisone 4 mg = methylprednisolone 0.8 mg
C. Side effects:
1) Cushing's syndrome, osteoporosis, myopathy, cataracts, peptic ulcers
2) Glucose intolerance, hypercholesterolemia, skin fragility, adrenal suppression
D. Interactions: None clinically significant
E. Use: Maintenance immunosuppression, rejection treatment
10. Immunosuppression: Early Rejection Prophylaxis
A. Standard Triple therapy
B. Preoperative
1) Cyclosporine: 2-6 mg/kg po based on renal function
2) Azathioprine: 4 mg/kg IV
C. Intraoperative
1) Methylprednisolone: 500 mg
D. Postoperative
1) Cyclosporine: 2-6 mg/kg po bid based on trough levels and renal function
2) Azathioprine: 2 mg/kg/day
3) Methylprednisolone: 125 mg IV every 8 hours for 3-4 doses, followed by prednisone
4) Prednisone: (beginning after Methylprednisolone)1 mg/kg/day tapering over 1 week to 0.5 mg/kg/day, followed by further tapering over 2-3 months to 0.2-0.3 mg/kg/day
E. Quadruple Therapy- OKT3 *
F. Preoperative
1) Cyclosporine: None
2) Azathioprine: 4 mg/kg IV
G. Intraoperative
1) Methylprednisolone: 500 mg
2) OKT3: 5-10 mg (or administer first dose of OKT3, 5 mg IV 24-48 hours postoperatively)
H. Post operative
1) OKT3: 5 mg/day IV for 7-10 days post operative
2) Cyclosporine: Beginning on the fourth post operative day, 2-6 mg/kg po bid based on trough levels and renal function
3) Azathioprine: 2 mg/kg/day
4) Methylprednisolone: 25 mg IV every 8 hours for 3-4 doses, followed by prednisone
5) Prednisone: (beginning after Methylprednisolone)0.25 mg/kg/day during the time of OKT3 administration. After OKT3 course completed, increase to 1 mg/kg/day for 7 days, then taper either completely off over 4 weeks or to 0.2-0.3 mg/kg/day by 1-3 months.
I. * OKT3 should be premedicated daily for three days with diphenhydramine 50 mg IV, acetaminophen 650 mg po or per rectum, and ranitidine 100 mg IV. OKT3should be post-medicated every 6, 12, and 18 hours after the first 3 doses with diphenhydramine 25 mg IV, acetaminophen 650 mg po or per rectum, and ranitidine 50 mg IV.
J. Quadruple Therapy - ATG/ALG/ALS**
K. Preoperative
1) Cyclosporine: None
2) Azathioprine: 4 mg/kg IV
L. Intraoperative
1) Methylprednisolone: 500 mg
M. Post operative
1) ATG/ALG/ALS: Daily dosing for 7-10 days, Dose depends on preparation
2) Cyclosporine: Beginning on the second or third post-operative day, 2 - 6 mg/kg po bid based on trough levels and renal function
3) Azathioprine: 2 mg/kg/day
4) Methylprednisolone: 125 mg IV every 8 hours for 3-4 doses, followed by prednisone
5) Prednisone: (beginning after Methylprednisolone) 0.25mg/kg/day during the time of ATG/ALG/ALS, followed by 1mg/kg/day for 7 days, then taper either completely off over 4 weeks or to 0.2-0.3 mg/kg/day by 1-3 months.
N. ** ATG/ALG/ALS should be pre-medicated daily with diphenhydramine 25-50 mg IV and acetaminophen 650 mg po or per rectum
11. Maintenance Immunosuppression Goal
A. Lowest overall level of immunosuppression to prevent rejection
B. Cyclosporine levels
1) Low therapeutic after 1-2 years
C. Azathioprine
1) 1-2 mg/kg/day after 1-2 years
D. Prednisone
1) 0 - 0.1 mg/kg/day after 1 year
12. Treatment of Rejection - Considerations
A. Histologic grade of biopsy
B. Allograft function
C. Time after transplantation
D. Past rejection history
E. Concomitant immunosuppression
F. Optimize cyclosporine/azathioprine
13. TREATMENT OF REJECTION
GRADE Mild
Moderate None or oral corticosteroid augmentation
Moderate Oral corticosteroid augmentation or IV corticosteroids
Severe TREATMENT IV corticosteroids and ATG/ALG OR OKT3
Immunosuppression Flow-chart
14. Other options
A. Alteration of maintenance regimen
1) Change from cyclosporine to Tacrolimus
2) Change from azathioprine to mycophenolate mofetil
3) Change from azathioprine to cyclophosphamide (vascular rejection)
B. Methotrexate course (2.5 - 7.5 mg. Q 12 hrs x 3 doses/week for 8-12 weeks)
C. Plasmapheresis (vascular rejection)
D. Total lymphoid irradiation
E. Photophoresis
F. Re-transplantation
EXTENDED OUTLINE
A. Major Histocompatability Complex (MHC)-prime physiologic role is to recognize “self” from “nonself”; in humans, this is known as the HLA system
B. HLA: class I—HLA-A, B, C; expressed on all cells of an organism. Class I molecules present antigenic peptides to activated T lymphocytes expressing CD8phenotype
C. class II—DP, DQ, DR; expressed on antigen presenting cells, e.g., B cells, T cells, macrophages, dendritic cells, and endothelium. Present to T lymphocytes expressing the CD4 phenotype.
D. Pivotal cells moderating rejection are the T cells expressing the CD4 complex. These T cells recognize foreign Class II antigens on antigen presenting cells (APCs)—these cells not only present, but also provide signals (lymphokines/adhesion molecules) for T cell activation (second signal). There are two pathways for this to occur—direct and indirect routes of sensitization
E. Activated CD4 cells are divided into Th1and Th2 populations: Th1 subpopulation produces: IL-2 (CD8 differentiation), INF (MHC class II differentiation), TNF (NO radicals/O2/Prostaglandins) Th2: IL-4,5,10—augments B cell mediated responses
G. Effectors of Graft Rejection:
1) CD8 activation is thought to involve recognition of class I antigen (first signal) in a setting of increased levels of IL-2 (second signal) secreted by activated CD4 cells. Graft destruction ensues.
2) Hyperacute rejection is secondary to pre-exisiting blood group antibodies, anti-MHC antibodies, or natural antibodies which react with the endothelial antigens—complement, coagulation, and kallikrein/bradykinin cascades activated. Leads to graft edema, hemorrhage, and vascular thrombosis.
3) Accelerated rejection from IgM/IgG antibodies formed in response to the donor graft. Biopsy shows vascular destruction with a paucity of cellular infiltrate.
H. Hallmark of cellular rejection is graft infiltration:
1) leukocyte attachment to the endothelium
a) mediated by cell adhesion molecules: selectins (rolling effect), integrins (bind the attached molecules), immunoglobin superfamily-related molecules. This is followed by diapedesis—ICAM-1 and LFA-1 interaction
2) transmigration through the vessel wall
3) migration within the graft
4) selective retention of activated cells in the graft
5) local proliferation of cells
1. Rejection Prevention
A. MHC matching
B. Immunosuppression
1) Cyclosporin (CyA) and FK506—inhibit lymphocyte proliferation and lymphokine production by binding to cytosolic intracellular receptors known as immunophilins (CyA-cyclophilins/FK506-FK506 proteins). These complexes inhibit calcineurin an intracellular protein phosphatase which plays a crucial role in the induction of lymphokine genes (IL-2). Side effects: renal dysfunction, GI, CNS, hypertension, and diabetes
2) Corticosteroids—negatively affecting the release of IL-1 and IL-6 from macrophages and thereby inhibiting IL-2 release. Side effects include hypertension, diabetes, cushingoid features, poor wound healing and asceptic bone necrosis
3) Azathioprine works non specifically by virtue of its antimetabolite effects to inhibit lymphocyte proliferation
4) OKT3—mouse monoclonal antibody against T cell receptor CD3 which nonspecifically suppresses all T cell functions. Use is generally in acute rejection episodes. Side effects: cytokine release causing fever, chills, and pulmonary edema; antibody production against the maurine antibody which precludes future courses; dramatic increase in lymphoproliferative disorders.
5) Rapamycin—homolog of FK506, but does not inhibit calcineurin. Mode of action is unclear. Has prevented development of cardiac allograft vasculopathy in rat allografts
6) 15-Deoxyspergualin (DSG)—binds cytoplasmic protein Hsc70 and interferes with antigen presentation and T and B cell development. Good for pancreatic islet cell survival. Causes myelosuppression
7) Mycophenolate mofetiln—inhibits inosine monophosphate dehydrogenase which blocks the de novo pathway for purine synthesis. This pathway is crucial for the proliferative response of T and B cell response. There is a low side effect profile.
8) Brequinar inhibits dihydrooratate dehydrogenase and blocks the de novo synthesis of pyrimidines. The proliferative response is attenuated.
C. Induction therapy
1) its use is associated with a greater cumulative rejection frequency
2) does not delay the onset of first rejection
3) does not reduce the cumulative number of episodes of rejection
D. Tolerance
1) refers to the elimination of the immune response to the antigens of the transplant while the immune response to all other antigens remains intact
2) Anergy—inactivation of cells reactive to the foreign antigen; thought to be the result of T cells binding specific antigen, but not receiving the appropriate second signal from APCs or CD4 cells. IL-2 experimentally has been shown to reverse this
3) Clonal deletion—elimination of cells reactive to the foreign atigen; occurs primarily in the thymus by a process known as negative selection
4) Suppression—suppression of cells responsive to the foreign antigens by another, regulatory immulogic process. Veto cell—inhibits the activity of T cells reactive with antigens on its surface thereby suppressing the activity of the attacking cells
2. Chronic Rejection
A. Cardiac allograft vasculopathy (CAV)
1) is now the leading cause of death or graft failure after the first year.
a) manifested by diffuse and accelerated form of coronary arteriosclerosis—often involves the full length of the artery.
2) virtually all transplant recipients have these findings.
3) rapidly progresses to vessel occlusion and MI
a) pathologic finding is a diffuse intimal thickening and perivascular inflammation extending from large epicardial arteries into medium sized arteries and arterioles
b) the endothelial response to injury theory likely forms the common bond; stimulated endothelial and smoth muscle cells produce cytokines and growth factors causing cell proliferation and smooth muscle and macrophage migration to the intima resulting in concentric lipid-laden calcium-poor plaque. There is evidence to document an inflammatory stage prior to the smooth muscle cell proliferation and also an impairment of endothelial-derived relaxation factor.
c) immune mechanisms are probably at work because the vasculopathy is selective for the allograft which it effects diffusely; the cause of the presumed endothelial injury is unknown
d)Risk factors??—lipid levels, hypertension, smoking, diabetes, and a history of previous atherosclerosis have not correlated with an increased risk of CAV. Only CMV infection has shown a strong association with either death or retransplantation from CAV.
4) use of dobutamine stress echocardiography to follow vs. angiography
a) best addressed by repeat transplantation although this is associated with a 30% or greater lower rate of survival
B. Xenotransplantation
1) widespread preformed antibodies in humans which are reactive for antigens of other species—e.g. pig to human transplant results in hyperacute rejection (discordant) [Concordant rejection is when closely related species reject transplants in a manner similar to allograft rejection]
2) cells and organs from one species may not be able to function in a xenogenic environment
3) cell mediated xenografic rejection may differ from allogeneic rejection and thus require different immunosuppression
4) the future may lie in manipulating the donor organ endothelial system expression of complement inhibitory proteins and therefore mediate hyperacute rejection by preventing complement activation.

Medical Complications of Cardiac Transplant
1. Cardiac
A. Ventricular dysfunction
B. Sinus node dysfunction
C. Tricuspid regurgitation
D. Allograft rejection
E. Allograft coronary artery disease
F. Decreased exercise tolerance
G. Infection
1) Bacterial
2) Viral
3 Parasitic
4) Fungal
H. Non-cardiac, Non-infectious
1) Renal insufficiency
2) Hypertension
3) Osteoporosis
4) Hyperlipidemia
5) Malignancy
6) Psychologic/behavioral/societal
7) Glucose intolerance
8) Pancreaticobiliary disease
9) Obesity
2. Cardiac Allograft Rejection
A. Propensity decreases with time
B. Types
1) Hyperacute
2) Acute
3) Chronic (ACAD)
4) Cellular
5) Vascular (Humoral)
C. Diagnosis
1) Endomyocardial biopsy
2) Non-invasive
3) Clinical
D. Treatment
Insertion of Bioptome
3. International Society for Heart & Lung Transplantation Endomyocardial Biopsy Grading Scheme
Grade Finding Rejection Severity
0 No infiltrates None
1A Focal (perivascular of interstisial infiltrates without necrosis Mild
1B Diffuse but not sparse infiltrate without necrosis Mild
2 One focus only with aggressive infiltrate and/or myocyte damage Focal Moderate
3A Multifocal addressive infiltrates and/or myocyte damage Moderate
3B Diffuse inflammatory infiltrates with necrosis Borderline severe
4 Diffuse aggressive polymorphous infiltrate with edema, hemorhage and vasculitis, with necrosis Severe
Cellular biopsy Cellular biopsy Cellular biopsy Angiogram Vascular biopsy
4. Allograft Coronary Artery Disease
A. Leading cause of death > 1 year after transplantation
B. Equivalent to:
1) "Chronic rejection" in renal allografts
2) "Vanishing bile ducts" in hepatic allografts
3) "Bronchiolitis obliterans" in pulmonary allografts
C. Prevalence of angiographically detectable disease
1) 1 year: 10-2O%
2) 5 years: 30-50%
D. Potential risk factors
E. Non-transplant specific
1) Age
2) Sex
3) Family history
4) Hypertension
5) Diabetes mellitus
6) Smoking
7) Hyperlipidemia
F. Transplant specific
1) HLA mismatch, at DR locus
2) Immunosuppressant drugs
3) CMV infection
4) Donor age
G. Symptomatic
1) Angina
2) Acute myocardial infarction
3) Sudden death
H. Asymptomatic
1) Coronary angiography
2) Nuclear (thallium/sestamibi)
3) Dobutamine stress echocardiography
4) Intravascular ultrasound
Vascular Lesion Survival post Angiogram Survival post Transplant Infection post Transplant
5. Infectious Complications
A. Phases
B. Early (< 1 month), Nosocomial Phase 1) Wound 2) Catheter-related 3) Hospital acquired pneumonia C. Middle (2-5 months), Opportunistic Phase 1) Toxoplasmosis 2) Herpes viruses (cytomegalovirus, herpes simplex) 3) Pneumocystis carinii 4) Nocardia 5) Fungi D. Late (> 6-12 months) , "Normal" Phase
6. Infectious Prophylaxis
Pathogenic Organism Prophylactic Agent
Cytomegalovirus Gancyclovir, Acyclovir, IVIg
Herpes simplex Acyclovir
Toxoplasmosis Pyrimethamine and Leucovorin
Pneumocystis TMP/SMX, Dapsone, Pentamidine
Oral candidiasis Nystatin, Mycelex troches
Malignancy
7. Malignancy
A. Incidence 1-2 %/year
B. Cutaneous Malignancy
1) Squamous cell carcinoma
2) Basal cell carcinoma
C. Lymphoma (PTLD)
1) Frequency: Most common tumor in cyclosporine-based immunosuppression
2) Timing: 12-18 months post transplant
3) Location: Intraabdominal most common
4) Etiology: B cell origin induced by Epstein-Barr virus
5) Treatment: Reduce immunosuppression
6) Acyclovir
7) Chemotherapy/radiation
8. Cyclosporine-induced Nephrotoxicity
A. Characteristics
1) Major decline in renal function in first 6 months
2) Disproportionate azotemia
3) Hyperkalemia
4) Increased uric acid levels
5) Mild proteinuria
6) Decreased fractional excretion of sodium
B. Pathogenesis
C. Renal vasoconstriction (afferent arterioles)
1) Prostaglandins
2) Endothelin
3) Direct effect on smooth muscle
D. Direct tubular toxicity
Hypertension and Renal Dysfunction
9. Cyclosporine-induced Hypertension
A. Incidence: 50-90% of heart transplant recipients
B. Occurrence: Weeks to months
C. Treatment goal: BP < 140/90 mmHg D. Moderate limitation of salt intake E. Maintenance of ideal body weight F. Moderate exercise G. ACE inhibitors (captopril, enalapril, lisinopril) H. Calcium channel blockers (diltiazem, nifedipine, verapamil, amlodipine, and others) I. Diuretics J. Others (Clonidine, B-blockers, hydralazine, prazocin) Hyperlipidemia and Diabetes 10. Hypercholesterolemia A. Incidence: 60-80% of heart transplant recipients B. Occurrence: - 8 months C. Magnitude: Increase of 30-80 mg/dl D. Positive relationship to: 1) Prior history of ischemic heart disease 2) Preexisting lipid abnormalities 3) Cumulative dose of corticosteroids 4) Cyclosporine E. Treatment goals: Serum cholesterol > 240 mg/Dl (or LDL cholesterol > 160 mg/dl)
1) Moderate limitation of fat intake
2) Maintenance of ideal body weight
3) Moderate exercise
4) Minimize corticosteroid dose
F. Gemfibrozil
G. HMG-CoA reductase inhibitors
1) Lovastatin
2) Simvastatin
3) Pravastatin
4) Fluvastatin
H. Bile acid sequestrants (Cholestyramine, Colestipol)
1) Nicotinic Acid
2) Probucol
3) Fish oil (Omega-3 Free Fatty Acids)
11. Osteoporosis
A. Incidence:
1) 10% of heart transplant recipients
B. Risk factors:
1) Corticosteroids
2) Older age
3) Lower bone mass before transplantation
4) Low cardiac output states
5) Prolonged use of loop diuretics
6) Physical inactivity
7) Cardiac cachexia
8) Heparin administration
9) Postmenopausal status

Myocardial Protection and Cardiopulmonary Bypass

Myocardial Protection and Cardiopulmonary Bypass
1. Myocardial Perfusion
A. Normally, subendocardial flow exceeds subepicardial flow
B. Myocardial perfusion, however, is altered by cardiopulmonary bypass
C. Narrow pulse pressure and variable mean pressure affects coronary perfusion pressure
D. Wall tension is increased in the empty, smaller heart
E. Ventricular fibrillation also increases wall tension
F. Regulatory and inflammatory factors are released which affect coronary resistance
G. Microemboli from the circuit and hemodilution impair oxygen delivery
H. Endothelial and myocardial edema further affect perfusion
I. Subendothelial vulnerability is increased by hypertrophy, coronary disease, fibrillation, cyanosis, shock, and chronic heart failure
J. The acutely ischemic heart may have poor reflow to the injured area
2. Myocardial Ischemic Injury
A. Acute ischemic dysfunction
1) Global myocardial ischemia
2) Reversible contractile failure, mostly from change in perfusion pressure
3) Immediate recovery as oxygen supply is restored
B. Stunning
1) Reversible systolic and diastolic dysfunction, no myocardial necrosis
2) Begins in subendothelium and progresses outward
3) May be accompanied by endothelial dysfunction
4) Results from ischemia-reperfusion insult, mediated by increased intracellular calcium accumulation
5) Recovery occurs within hours to weeks
C. Hibernation
1) Reversible chronic contractile depression
2) Related to poor myocardial blood flow
3) Recovery occurs within weeks to months
D. Necrosis
1) Irreversible ischemic injury with myocardial necrosis
2) Hypercontracture occurs first in the subendothelium and is more rapid in the hypertrophied heart
3) Typically results in contraction band necrosis, rarely "stone heart"
4) Osmotic and ionic dysregulation produce membrane injury and myocyte lysis
3. Cardioplegia
A. Studies in animals have inconsistent correlation with clinical results due to species differences, extent of disease, and perioperative events that precipitate, extend, or enhance myocardial damage
B. The goals of cardioplegia are to protect against ischemic injury, provide a motionless and bloodless field, and allow for effective post-ischemic myocardial resuscitation
C. Cardioplegic techniques vary according to perfusate (blood vs. crystalloid), duration (continuous vs. intermittent), route (antegrade vs. retrograde), temperature (warm vs. cold), and additives
D. Special consideration is required for the acutely ischemic heart and the neonate
4. Mechanisms of Cardioplegic Protection
A. Mechanical arrest (potassium-induced) will reduce oxygen consumption by 80%
B. Hypothermia will reduce consumption by another 10-15%
C. Aerobic metabolism can be maintainted with oxygenated cardioplegia
D. Hypothermic arrest is sustained with readministration every 15-30 minutes
E. Retrograde delivery protects the left ventricle more completely than the right ventricle
F. Prevent myocardial rewarming with systemic hypothermia, aortic and ventricular vents, and caval occlusion
G. In acute ischemia, use warm induction with substrate enhancement (glutamate, aspartate)
H. Reperfusion should be controlled, using warm, hypocalcemic alkaline cardioplegia
I. This approach combats intracellular acidosis and rapid calcium infusion injury
J. Retrograde or low-pressure antegrade perfusion is preferred for reperfusion
K. Ensure uniform warming
5. Neonates and Children
A. Children older than 2 months have similar myocardial physiology to adults
B. The neonatal myocardium, however, is different in several ways
C. Hypoxia is more easily tolerated
D. There are greater glycogen stores and more amino acid utilization
E. ATP breakdown is slower due to deficiency in 5' nucleotidase
F. Multidose cardioplegia is disadvantageous
G. Cyanosis may worsen resistance to ischemia
H. Amino acid substrate enhancement is beneficial
6. Cardioplegia Composition
A. Blood has the advantage of oxygen carrying capacity, histidine and hemoglobin buffers, free radical scavengers in RBCs, and metabolic substrates
B. Blood also has improved rheologic and oncotic properties, which may lessen myocardia edema
C. Buffers such as THAM, histidine, and NaHCO3 form a slightly alkaline solution for reperfusion that can counteract intracellular acidosis
D. Small amounts of calcium (0.1-0.5 mM/L) restores calcium that has been chelated by citrate
E. Potassium concentrations range from 10-25 mM/L, with the first dose being the highest
F. Other substrates are being evaluated, including allopurinal, SOD, deferoxamine, adenosine, nucleoside transport inhibitors, and potassium-channel openers
CARDIOPULMONARY BYPASS
1. The Circulatory Environment
A. Cardiopulmonary bypass is an abnormal circulatory state
B. Non-pulsatile flow, hemolysis, hemodilution, foreign surface exposure, general stress response, and the inflammatory response all contribute
C. Mechanial components
1) Roller pumps are slightly non-occlusive, resistance-independent, and may cause less blood trauma
2) Centrifugal pumps are dependent on inflow or outflow resistance; will cease flow at very low inflow resistance and very high outflow resistance
3) Venous drainage can be active or siphoned
4) Active drainage requires vacuum through the venous reservoir or negative pressure from the pump
B. Heat exchanger
1) The cooling or warming gradient is usually within 10-14 degrees of the patient's temperature
2) This minimizes the tendency for gas to come out of solution and risk of air embolism
3) Mixed blood temperature should be less than or equal to 38.5C
4) The water bath should stay between 15 and 42C to prevent organ damage (too cold) and hemolysis (too warm)
C. Oxygenator
1) Largest foreign surface contact area
2) Membrane oxygenators can be microporous, hollow fiber, or silastic (true membrane)
3) Gas flow is titrated to maintain PaO2 between 85 and 250mmHg to avoid O2 toxicity
4) PCO2 is regulated by gas and blood flow through the membrane
5) pH is controlled by adjusting the PaCO2
6) alpha stat adjusts the pH to 37C, with the goal of providing optimal enzymatic function during hypothermia
7) pH stat corrects the pH to the temperature of the patient's blood, with the goal of relative hypercarbia to increase cerebral blood flow
2. Mechanisms of Injury
A. Mechanical
1) The foreign surfaces of the bypass circuit (boundary layer of oxygenator, heat exchanger, filters, tubing) interact with the blood
2) Shear stresses include the pump, cardiotomy suction, and cannulae
3) Microemboli can form as particles from the oxygenator, platelet aggregate, or fibrin aggregates, and are greatest within the first 15 minutes of bypass
B. Humoral
1) Factor XII (Hageman factor), the alternative complement cascade (C3a), kallekrein, and plasminogen are activated in various degrees
2) Other factors interrelate and amplify the inflammatory reaction, including the arachidonic acid cascade, interleukins, TNF, and PAF
C. Cellular
1) Neutrophils play a major role in humoral activation and are sequestered in the lung, releasing cytotoxin and free radicals which increase vasoreactivity and vascular permeability
2) Monocytes and mast cells also participate, although their role is unclear
3) Lymphocytes have a minor role, if any
4) Platelets are activated and elaborate GPIB, IIB, and IIIA
5) Absolute number of platelets is reduced by 40% by the end of bypass, and the number of receptors is also decreased
6) Endothelial cells are affected by abnormal flow, humoral factors, and local ischemia
7) A wide variety of substances are expressed by the endothelium, including prostaglandins, thromboxanes, leukotrienes, and interleukins
3. Miscellaneous
A. Circulatory arrest with profound hypothermia (18-20C) is generally safe up to 45 minutes
B. Over 60 minutes is associated with increased incidence of neurologic deficit
C. The period between 45 and 60 minutes is unclear, as histologic injury seems to be greater than functional injury
D. Maintain a gradient of 4-6C, as rapid cooling produces uneven cerebral cooling
E. Retrograde and low flow cerebral perfusion are currently being evaluated
F. Pulsatile flow has not been shown to be superior to non-pulsatile flow
G. Lower ACT of 300-350 seconds is not associated with greater complications compared to standard ACT of 450
H. Aprotinin will elevate the ACT (600-800), neutralizes the kallikrein cascade, and protects platelet receptors
I. Protamine reactions occur through the classical component pathway and cause direct myocardial depression

























Minimally Invasive Cardiac Surgery
1. History
A. Beating heart anastomosis
1) Alexsis Carrell on dog
2) Kolessov 1967 first LIMA to LAD (6 pts)
3) Banned/ Buffalo 1990/1991
4) Subramanian/Acuff/Mack/Calafiore - MIDCAB
2. Port Access Cardiac Surgery
A. CABG -- Stevens 1996 (Stanford)
B. MVR -- Schwartz, Ribakove (NYU)
C. MIDCAB --
D. Exposure thru 4th ICS
E. 1 or 2 vessel bypass
F. 5-20% stenosis rate
G. Anterior wall revascularization only
H. Less use of resources
I. Eliminates CPB and sternotomy
3. OPCAB
A. Exposure median sternotomy
B. Bypass multiple targets
C. Patency unknown
D. No CPB
E. Port access
F. 4th ICS
G. Femoral cannulation CPB
H. Still heart
I. Total revascularization
J. Can use SVG for proximals
K. Over 2000 cases done similar results as open
4. Endoscopic CABG
A. LIMA taken down with scope only
B. Then conventional MIDCAB or Port Access
5. MIDCAB or OPCAB
A. Use in patients you might not want to use CPB
B. Calcified aorta, poor LVEF, severe PVD
C. Severe COPD, CRF, coagulopathy
D. Transfusion issues, i.e., Jehovahs witness
E. Good target vessels not diffuse disease
F. Anterior/lateral wall revascularzation
G. Target revascularzation in older sicker patients
6. Port Access
A. More universal use
B. Multi-vessel revascularization
C. Redo cases
D. Where sternum healing is problem
E. Obese, DM, steroids
7. Aortic Valve surgery
A. Approach
1) Right parasternal first used by Cosgrove 2nd and 3rd costal cartilages
removed try to preserve RIMA
2) Mini sternotomy (Gundry) upper sternotomy T off to the right 3rd or 4th
ICS better for homograft root replacement
3) Transected sternum (Cosgrove) transect at 3rd ICS level both RIMA and LIMA divided
8. Mitral Valve Surgery
A. Approach
B. Right parasternal
C. Lower mini sternotomy
D. Right anterior lateral thoracotomy
E. CPB has been accomplished with Heartport system
F. Fem-fem CPB
G. Direct cannulation of aorta and atrium
9. Advantages
A. Decreased length of stay (average 4 days)
B. Decreased blood transfusions (Cohn, et al)
C. Return to activity sooner
D. Less atrial fibrillation (5-10% incidence vs 20-30% open CPB)
10. Pediatric Cardiac Surgery
A. Ligation of PDA and division of vascular rings via thorascopic technique (Burke)
B. Open procedures VSD, Tetralogy via mini-sternotomy (Gundry)
C. ASD closure with Heartport port access
Mini L-Shaped Sternotomy
Mini T-sternotomy
Mini- Parasternal & Mini-Thoracotomy
D. Graphs
AF Incidences
Patency Rates
Long-Term Results
Angiographic Results
Postoperative AF
Decision Grid
Sternotomy vs No Sternotomy
Off-Pump Indications
11. Future robotics
A. 3-D imaging
B. Total closed chest still experimental
C. What to do?
D. All will become tools to be used
E. Each will find a niche
F. How to define role for each tool
G. Balance co-morbidities with complete revascularization

















Aortic Aneurysm
1. Morphology
A. Atherosclerotic (degenerative) aneurysm: most common cause (1/2) of localized aortic enlargement
B. Chronic aortic dissection: persistent false channel of outer media and adventitia gradually enlarges
C. Chronic traumatic aortic transection: false aneurysm contained only by aortic adventitia
D. Annulo-aortic ectasia: aneurysmal dilation of sinuses of Valsalva (Marfan, cystic medial necrosis)
E. Aortitis: granulomatous or syphilis
2. Location
Ascending aorta 45%
Arch 10%
Descending thoracic 55%
Thoracoabdominal 10%
3. Symptoms
A. Usually asymptomatic
B. Pain implies sudden extension or rupture of aneurysm
1) Ascending aorta - neck, jaw
2) Descending aorta - back, inter-scapular
3) Thoracoabdominal aorta - low back
C. Compression of adjacent structures
1) SVC syndrome
2) Hoarseness, laryngeal nerve
4. Associated Atherosclerotic Disease
Coronary arteries 16%
Cerebrovascular 10%
Peripheral vascular 10%
Abdominal aortic aneurysm 10%
5. Diagnosis
A. Chest X-ray - enlarged aortic shadow
B. Aortography - most valuable for assessment of aorta proximal and distal to aneurysm
C. Echocardiography - is useful in the assessment of aortic valve function and can demonstrate an intimal flap.
D. Computed axial tomography - real size of aneurysm and relation to adjacent structures
E. Magnetic resonance imaging - multiple planes possible, cine loop
6. Natural History
A. Aortic aneurysms enlarge, eventually rupture (74%)
B. Large aneurysms(>6 cm) tend to rupture
C. Symptoms herald rupture (2 years)
D. Aneurysm with chronic dissection have worst prognosis
7. Operations - Ascending Aorta and Arch
A. Conventional cardiopulmonary bypass is utilized
B. Aortic valve replacement with valved conduit (Bentall procedure)or repair/resuspension if feasible
C. Arch anastomosis by tailoring or arch vessel reimplantation
D. Reimplant the coronary arteries as buttons
E. Do not cover the graft, as this will increase the risk of false aneurysm
F. Elephant trunk
G. Cerebral perfusion antegrade ? retrograde
H. Deep hypothermia - circulatory arrest
8. Operation - Descending Thoracic Aorta
A. Clamp and go is the traditional method
B. Incise the aneurysm to work inside
C. There are many approaches to protect the spinal cord and kidneys, including:
1) NTP and spinal fluid drainage are somewhat controversial
2) LV or ascending aorta to descending aorta shunt (Gott)
3) LA to femoral artery bypass
4) Femoral-femoral cardiopulmonary bypass
5) Deep hypothermia and circulatory arrest may be the most controlled approach
D. The proximal anastomosis should be precisely matched to the aorta
E. Reattach the intercostal arteries as an island; this is particularly important in the distal portion of the repair
F. The distal anastomosis may be fashioned either end-to-end or as an elephant trunk
9. Operation - Thoracoabdominal Aorta
A. Spinal cord and renal protection are essential
B. Hemorrhage remains a challenging problem
C. Thoracoabdominal incision with a retroperitoneal approach
D. There are also various approaches to these aneurysms:
1) Clamp and go with or without heparinization
2) Deep hypothermia with circulatory arrest
E. Reimplant the visceral and intercostal-lumbar arteries when involved
10. Results
Death (hospital) - bleeding, neuro, MI
Ascending aorta 4-10%
Arch 5-50%
Descending 5-15%
Thoracoabdominal up to 50%
Survival - new aneurysm, CHF, renal
5 years 60%
10 years 40%




Acute Aortic Dissection
Definition
Dissection of the aorta is an event that results in the separation of the layers of the media by blood, producing a false channel with variable proximal and distal extension.
1. Etiology
A. Cystic medial necrosis - 20%
B. Marfan syndrome - 20-40%
C. Other causes: hypertension, bicuspid aortic valve/aortic stenosis, atherosclerosis, coarctation, pregnancy, trauma, aortic cannulation, aortic cross-clamping, cardiac catheterization
2. Morphology
A. Blood leaves the normal aortic channel through intimal tear, rapidly dissecting through the media to produce a false channel
B. The intimal tear is sometimes absent; possible rupture of vasa vasorum with medial hemorrhage
C. Usually the dissection proceeds distally; 38% dissect proximally and 10% in the transverse arch
D. Dissection may shear off or extend into branch arteries
E. False channel characteristics:
1) Thickens and gradually enlarges with time
2) May interrupt blood supply of branches by ext ernal compression
3) Outer wall thin - media + adventitia
4) May rupture to pericardium or pleural space
5) May thrombose
3. Classification
A. Acute = less than 2 weeks, chronic = greater than 2 weeks
DeBakey I Ascending + arch Stanford A
DeBakey II Ascending only Stanford A
DeBakey IIIa Descending only Stanford B
DeBakey IIIb Descending + abdom Stanford B
4. Clinical Features
A. Severe pain - tearing, interscapular, precordial, neck, migrating, persisting
B. Signs of occlusion of major vessel
1) Arch - stroke, syncope
2) Intercostal - paraplegia
3) Renal - oliguria-anuria
4) Iliac - ischemic leg
C. Sudden death
1) Rupture to pericardium, pleural, peritoneal space
2) Shear off coronary artery
D. Hypovolemic Shock
1) Blood in periaortic tissues
2) Acute aortic valve insufficiency
3) Cardiac tamponade
5. Diagnosis
A. Imaging
1) Chest X-ray - widened mediastinum, cardiomegaly, pleural effusion, intimal calcification separated more than 6mm from the edge
2) Echo - identifies intimal flap/false channel, noninvasive, no contrast media, performed at bedside
3) TEE is best for the descending aorta; TTE best for the ascending aorta and arch
4) Aortography - conventional method of diagnosis (gold standard), shows origin of arteries from true or false lumen
5) CT Scan - identifies intimal flap rapidly, requires contrast media
6) MRI - multiple planes, cine for AI
B. Main points of interest
1) Involvement of the ascending aorta
2) Location of the intimal tear
3) Status of perfusion in the major branches
4) Size of the aorta and presence of AI
5) Extent of the false lumen
6) Pericardial effusion
6. Treatment Overview
A. Type A and complicated type B dissections are managed surgically
B. Uncomplicated type B dissections are managed medically
C. The goals of surgical therapy are to prevent extension, excise the intimal tear, and replace the segment of aorta which is susceptible to rupture
D. The goals of medical therapy are to prevent extension, control blood pressure, and relieve pain
7. Treatment - Ascending Aorta
A. Immediate operation is indicated because rupture is likely
B. Contraindications: ? advanced age, incurable coexisting disease, paraplegia
C. Note: new stroke may resolve, not a contraindication
D. Replace ascending aorta and the aortic valve if insufficient; the valve may be worth preserving if normal
E. Replace arch if false channel leaking or site of tear
F. Operative strategy (elephant trunk)
1) Use circulatory arrest if indicated
2) Incise in a longitudinal fashion, avoiding the phrenic and recurrent nerves
3) Follow the dissection from inside the aorta to determine extent and remove damaged intima and media
4) Invert the graft into the distal aorta and approximate only the aortic adventitia to the inside of the graft
5) Pull the graft out and anastomose the arch vessels as a group
6) Once the distal repair is completed, the proximal repair can be performed with the graft clamped in a fashion that allows reperfusion and rewarming of the body while the proximal aspect of the repair is completed (with continued protection of the heart with cardioplegia)
8. Treatment - Descending Aorta
A. Medical treatment indicated unless complications of dissection have occurred
1) NTP + beta-blocker to maintain normal blood pressure
2) 80% survive 1 year
3) Close follow-up required, 50% die in 3-5 years
B. Complications dictate immediate operation (interposition graft or fenestration)
1) Hemothorax, persisting pain, limb ischemia, acute renal failure, paraparesis (malperfusion syndrome)
2) Paraplegia NOTan indication for operation because not likely to resolve
9. Results After Operation
A. Early (hospital) death
1) Ascending aorta - 5-10% (up to 30%)
2) Arch - 10-25% (up to 50%)
3) Descending - 10% (up to 25-60%)
B. 10 year survival - 46%
1) 1/3 late death related to residual old false channel or redissection
C. Aneurysm of false channel
1) Uncontrolled hypertension - 50%
2) Controlled blood pressure - 10-20%
D. Redissection - 10% (Marfan higher)









































































































Selection of Prostheses
1. Mechanical valves
A. Selection
1) <70 yo 2) no h/o bleeding B. Survival - over ½ of late deaths are related to valve complications C. Hemodynamics 1) Tilting disc and bileaflet are “low-profile” a) Tilting disc - 6-7mmHg gradient 2) Caged ball is “high-profile” D. Thromboembolism 1) Highest risk is in first 14 months 2) Steady level after - 0.5%/pt-yr 3) INR 2.5 = therapeutic 4) Coumadin for all - antiplatelet agent for high-risk (a-fib, h/o embolus, etc.) 5) Thrombolytic therapy - never for patients in a low-output state E. Hemorrhage 1) Incidence the same for aortic and mitral position 2) Associated w/high anticoagulation levels (INR >4.5)
3) At INR 2.5-3.5, anticoagulation-related death = 0.2%/pt-yr
F. Endocarditis
1) PVE - mortality = 23-69%
2) Most commonly in first several months
3) After initial period = 0.17%/pt-yr
G. Periprosthetic leakage (see Table 122-2)
1) Predisposing factors
a) Annular calcification
b) Infection
c) Annuloprosthetic mismatch
d) Excessive tension on sutures, annulus or both
e) Technique
f) Abnormal annulus tissue
H. Structural valve degeneration
1) Rare
2) Leaflet fracture - may be due to mishandling à scratches
I. Nonstructural valve degeneration
1) Pannus formation
2. Bioprosthetic Cardiac Valves
A. Features
1) No indication for anticoagulation
2) Survival
B. Glutaraldehyde-preserved porcine valves
C. Hemodynamics
1) Central unimpeded flow
2) In aortic position, small (19-21mm) valves are stenotic
3) Supraannular bioprosthesis improves flow
D. Thromboembolism
1) INR 2.0-3.0 for a-fib
E. Hemorrhage-see Table 122-4
F. Structural valve dysfunction
1) Progressive degeneration
2) Reasons
a) Calcification
b) Collagen degeneration-associated cuspal defect
c) Time-dependent - accelerated failure after 8-10 years
d) Valve failure and calcification accelerated in childrenàyoung adults
e) Mitral > aortic failure
G. Endocarditis
H. Periprosthetic leak
3. Pericardial Valves
A. Better flow (than porcine bioprostheses)
B. Newer designs more durable
4. Homograft Valve Prostheses
A. Patient survival 85-90% @ 7.5yr // 71% @ 14yr
B. Durability
1) Early homografts - calcification & cusp rupture
2) Cryopreservation (vs irradiation & chemical processes)
a) 95-98% freedom from structural deterioration (10yr)
C. Thromboembolism
1) ? Role of endothelium
D. Endocarditis
1) S. aureus a major player
2) Many respond to Abx
3) Failure to respond to Abx = surgical indication