Case

The death of this middle-aged man several weeks after an interventional catheterization and coronary artery procedure resulted in a suit against the treating cardiologist. The claim against the physicians is based on the performance of an unjustified procedure in lieu of recognized interventions with high clinical success and low morbidity or mortality, such as undertaking a coronary artery bypass or a balloon angioplasty with stenting. It is also suggested that the failure to adequately follow the patient after the procedure contributed to his death. The further claim was that the unjustified procedure not only did not improve the coronary stenosis, but actually directly contributed to his death through unexpected complications. The first claim may be countered by establishing that the decision to carry out the procedure is a matter of medical judgment and not negligence, and the lack of follow-up may have been the result of patient uncooperation. However, it would be very difficult to argue that the improper procedure did not negligently cause this patient's death, as will be established below.

This 51 year-old man, with a strong family history of coronary artery disease, complained of new onset chest pain. He had undergone a relatively recent screening procedure, ultrafast CT scanning, which revealed significant calcium scores in his coronary arteries. This test has received much hype in the medical community over the last 5 years, as a non-invasive test to determine the presence of coronary disease. It has yet to be established prospectively that the claims for the test's sensitivity or specificity are scientifically justified. There is evidence that coronary atherosclerosis (particularly vulnerable plaques with high susceptibility to rupture, associated with unstable angina or myocardial infarction) may have minimal or no calcification; and calcification is not necessarily an indication of luminal occlusion or narrowing. Obviously, a positive test that then leads to a positive confirmatory finding is valuable; however, a negative test may not rule out the potential for a serious coronary lesion. Ultimately, it will have to be determined that the benefit of the test justifies its cost.

Regardless, in this symptomatic patient the test was positive, and it led to coronary catheterization that demonstrated severe complex stenoses of the proximal left anterior descending coronary artery (LAD), and high grade stenosis of the mid-right coronary artery (RCA). The left circumflex artery (LCX) was apparently had minimal involvement. With two-vessel disease, particularly with involvement of the proximal LAD, it would have been prudent to recommend coronary artery bypass grafting (CABG). The LAD could have been bypassed with an internal mammary artery with a very high guarantee of long-term success, since the internal mammary artery is minimally susceptible to atherosclerotic stenosis. The RCA would have required either a vein-graft, or a free arterial graft with a radial artery. This procedure, particularly in a young man with no prior cardiac damage, could have been performed with very low morbidity, and a mortality rate of at most 1-2%. The survival of the grafts could be estimated in the range of 15-20 years, or more.

A considerably riskier approach would be to perform a balloon angioplasty with stenting. This is potentially dangerous with proximal lesions, particularly when there are multiple sites within the same vessel, along with high-grade disease in another major vessel. The placement of stents would function to maintain vessel patency post-angioplasty. Angioplasty, however, does have the significant potential of re-stenosis, with a rate of 30-40% in the first 3-4 months after the procedure, and a slowly progressive increase thereafter. Although somewhat ameliorated with the use of stents, re-stenosis can occur, and occasionally even at an accelerated rate. Moreover, with multiple sites of stenosis in the LAD, the vessel would have required multiple stents. Although technically feasible, this may prolong the procedure and make the left ventricle susceptible to ischemia or infarction.

The procedure that was employed known as atherectomy, is rarely used today, since it was supplanted clinically by angioplasty and stenting in the mid 1990's. Atherectomy uses a variety of cutting catheters, including sharp blades or rotating blades (and experimentally, lasers), to excise plaque material from the vessel wall and re-establish an adequate lumen. The plaque material is then suctioned through the coronary catheter, and removed from the patient. Atherectomies became valuable source of research tissue in a number of centers investigating atherosclerosis and re-stenosis, since it was the only methodology that provided fresh atheroma for biochemical, histochemical, or molecular studies. The tissue fragments were composed of all of the elements of atherosclerotic plaque including fibrofatty tissue, lipid core, calcium, and inflammatory cells. Not infrequently, segments of medial smooth muscle were included; yet, there was only a rare case of actual coronary artery rupture that required surgical intervention. Complications other than vessel rupture include vessel collapse or spasm, coronary dissection, and lumen thrombosis. These complications are prevented by stenting, which can be used with atherectomy. In this case, stenting or removal of plaque debris was not performed. There has been some concern about this approach over the years, but there are few clinical data to demonstrate a potential adverse affect of allowing fragments of plaque (even microscopic) to embolize downstream in the coronary circulation.

This patient had an apparently successful procedure carried out in the LAD and RCA on separate days. He allegedly had good coronary flow with widely patent vessels and no residual stenosis. He did have bleeding complications at his arteriotomy site, but this is not unusual. He also had minor elevations of creatine kinase (CK), with a significant increase of his

MB iso-enzyme after the LAD procedure. He was maintained on aspirin prophylactically. Approximately 3 weeks after the procedure, he returned to his executive position overseas. On the following day, he collapsed suddenly and died. The autopsy was carried out in a well-recognized academic center with sophisticated knowledge of cardiovascular disease.

Before actually turning to the specific autopsy findings and discussing them in detail, it might be worthwhile to address this patient's death from a clinical perspective. What are the likely cause(s) of his sudden cardiac arrest? Although some unrelated event only indirectly related to the coronary artery procedure could have occurred (e.g. stroke), the temporal proximity to the cardiac catheterization and intervention, strongly suggests an association. Acute coronary occlusion is a likely cause, with several etiologies possible. Neo-intima proliferation, thrombosis, and vessel trauma should be considered. As a general rule, neo-intimal proliferation leading to re-stenosis requires months to develop sufficiently to cause coronary artery ischemia; although the process may have begun over 3 weeks, it is not likely to cause sufficient occlusion to lead to ischemia and arrhythmia. There could have been an acute thrombus developing at an atherectomy site with sudden myocardial ischemia or infarction. Thrombus, however, is much more likely to develop shortly after the procedure, not weeks later. There could have been a 'silent' complication of the atherectomy and balloon angioplasty such as a delayed rupture of a pseudo-aneurysm (e.g. disruption of the vessel during the procedure leading to a localized hematoma that then ruptured weeks later with pericardial tamponade). There also could have been a dissection of the coronary artery with a delayed rupture. If any of these complications had actually been the cause of death, then the medico-legal aspects of this case would have focused on the utilization of the atherectomy procedure rather than coronary artery bypass grafting.

What did happen? In fact, 3 things occurred that together contributed to his death:

1. Persistence of high-grade coronary stenosis

2. Focal coronary artery dissection that contributed to the stenosis

3. Multi-focal myocardial necrosis secondary to embolization of plaque debris and other foreign material

We will address each of these processes.

High-grade Coronary Artery Stenosis: Despite the clinical impression that following the atherectomy and balloon angioplasty there was wide patency of all coronary arteries, the autopsy showed otherwise. The left main coronary artery (LM) was narrowed 50-75%, the LAD and RCA were 90% occluded focally, and the LCX was 75% occluded. Although it is possible that there was a complete mis-reading or inaccurate reporting of the actual degree of coronary artery patency, it is more likely that other related phenomena can explain this significant discrepancy. There often is an angiographic underestimation of coronary lumen narrowing. This almost certainly accounts for the presence of high-grade stenoses in the LM and LCX, since these vessels were not manipulated, and it cannot be assumed that they developed severe atherosclerotic disease in 3 weeks. If a vessel has an eccentric lumen, the angiographic dye may fill a flattened oval or slit-like lumen; if viewed perpendicular to its wide axis, the vessel may appear to have a larger lumen (since the dye is only visualized in 2 dimensions). Ordinarily, by rotating the angle of view, this effect should be minimized or eliminated, but it is not unusual to find a lack of close correlation between angiographic and post-mortem estimates of coronary patency.

The vessels that were instrumented with the atherectomy device and the angioplasty balloon, may have undergone post-procedure remodeling. In other words, because of medial smooth muscle stretching immediately following the intervention, the vessel lumens may have appeared larger than they actually were. Subsequently, the media may have recovered its tone, and elastically rebounded to a smaller diameter. This effect is prevented by the placement of a metallic stent, which maintains a fixed lumen diameter.

At the time of autopsy, the third contributor to significantly smaller caliber vessels was the development of coronary artery spasm. Although often occurring at the time of the procedure, spasm of multiple coronary vessels may occur at the time of cardiac arrest. Sometimes, when localized, it may be the actual cause of the arrest; whereas, when generalized it is more likely associated with a high output of catecholamines and other stress hormones. The vascular spasm may be prevented with intra-coronary stenting, but if persistent post-mortem, it may affect the estimation of the lumen diameter.

In this case, it appears most likely that the marked discrepancy between the coronary artery lumens post-intervention, and the findings at autopsy, were due to mis-interpretation of the angiograms, and the effects of re-modeling of the vessels with subsequent recovery.

Focal Coronary Artery Dissection: The autopsy also demonstrated a dissection of the lAd outer media (Figure 90), which was a direct unrecognized complication of the procedure. The occurrence of this event could be dated with certainty to the time of the atherectomy and angioplasty, since the dissected false lumen had maturing granulation tissue within an organizing thrombus that was approximately 3 weeks in age. It probably resulted from the balloon angioplasty, since in the intima overlying the dissected channel, there was a thin layer of loose connective tissue consistent with an early neo-intima, within which fibromyoblasts were proliferating. The association of coronary dissection and angioplasty is common; in the present case it contributed to a focal area of LAD stenosis. Moreover, dissection can also be prevented or minimized with the use of infra-coronary stents.

Multi-focal Myocardial Necrosis: Throughout the left ventricle and in a few areas of the right ventricle, there were multiple foci of sharply demarcated, small areas of myocardial necrosis, known as myocytolysis. These foci were generally in the range of 200-500 microns, with infiltration by mononuclear inflammatory cells (lymphocytes and monocytes), and histiocytes. The histiocytes had phagocytized myocyte cell debris, including lipofuscin. Within the foci, myocytes were generally completely destroyed with empty 'ghosts' maintaining myocyte shape and size; hence the term myocytolysis. Some organization, with in-growth of connective tissue was present, consistent with a process that was about 2-3 weeks old.

Most significantly, in many small intra-myocardial arteries in the general vicinity of the foci of myocytolysis, there was tissue debris within the vessel lumens. Some of the debris was calcified, and some was clearly recognizable as atherosclerotic plaque material. In one somewhat larger infra-myocardial artery, there was foreign (non-biological) material, consistent with some type of fiber (possibly cotton) (Figure 91) and/or plaque debris, which elicited a local giant cell reaction. The plaque emboli were predominantly subepicardial and mid-wall vessels, although occasionally they were seen in the subendocardium.

Clearly, this embolic biologic and foreign material was secondary to the two atherectomy procedures. The dating of the focal myocytolysis associated with the emboli, provides a temporal relationship to the coronary intervention occurring 3 weeks before death. It is noteworthy, that at the time of the atherectomy, the patient developed an abnormally elevated creatine kinase, with a positive MB fraction. This was not considered to be significant clinically. Yet, in retrospect, the elevated CK enzyme was due to multi-focal small areas of reperfusion myocardial necrosis secondary to coronary micro-emboli. Whether it was the multiple areas of healing necrosis with surrounding viable but ischemic myocardium, or whether it was the severe high-grade coronary disease with ischemia that elicited a sudden fatal arrhythmia, cannot be determined; however, either could have done so. Both entities represent significant complications of the original procedure; neither would have occurred if this patient had been treated with CABG, or even angioplasty with stenting.

A final point relates to the pathogenesis of myocytolysis, and the potential role of coronary micro-emboli. Myocytolysis is a type of reperfusion necrosis associated with an abnormal microcirculation. As described elsewhere in this book, the coronary microcirculation is an end-vessel network; thus, distal arterioles supplying capillaries and small volumes of myocardium, do not anastomose with other arterioles. If those arterioles or more proximal small intra-myocardial arteries develop spasm, the myocardium supplied by those vessels may develop a type of reperfusion necrosis (e.g. there is initially ischemia, followed by blood flow). This causes free radical damage to the myocyte, with rupture of the sarcolemma and an influx of calcium into the cell causing an 'explosive' type of necrosis (hence, lysis). Most often, there are concurrent high-catecholamine states such as shock; however, other vasoactive substances can cause microvascular vasospasm. Myocytolysis is a very common finding in cardiomyopathies of many etiologies, myocarditis, and ischemic heart disease.

Although it is logical to assume that micro-embolization would cause localized myocyte necrosis due to obstruction of the vessels, in fact, the morphology of the microscopic necrosis with areas of contraction bands (a reperfusion lesion that precedes myocytolysis) or myocytolysis, suggests a reperfusion process. Experimentally, embolization of 25 and 50 micron-sized microspheres into the coronary circulation of animals led to identical areas of microscopic necrosis as seen in this case. Interestingly, treatment of the animals with drugs that prevent coronary artery or microvascular spasm (calcium channel blocking drugs, or alpha-adrenergic blocking drugs), significantly prevented the necrosis even with the microspheres in the circulation. Thus, it is not obstruction, but spasm that leads to myocytolysis. The plaque emboli caused multiple areas of microvascular spasm and myocyte necrosis in this patient. It is not known where the foreign fiber material came from, but it is likely to have been a contaminant of one of the coronary catheters. Since the sections of myocardium that demonstrated these changes were randomly sampled (e.g. the pathologist performing the autopsy did not see any grossly visible areas in the myocardium to sample specifically), then the plaque emboli, and probably the foreign material, were probably a generalized and widespread phenomenon throughout the heart.

In summary, this case has many interesting clinical and pathological features, but it also clearly indicates why it led to a negligence suit against the cardiologists performing the coronary interventional procedure. The wrong treatment, and its subsequent complications, was medical negligence that unfortunately caused the death of this treatable patient.

Suggested Readings

1. Carroza JP Jr, Braim DS. Complications of directional coronary atherectomy: incidence, causes, and management. Am J Cardiol. 1993; 72: 47E-54E.

2. Hinohara T, Robertson GC, Selmon MR, Vetter JW, McAuley BJ, Sheehan DJ, Simpson JB. Directional coronary atherectomy complications and management. Cather Cardiovasc Diagn. 1993; Suppl 1:61-71.

3. Kaufmann UP, Meyer BJ. Atherectomy (directional, rotational, extractional) and its role in percutaneous revascularization. Curr Opon Cardiol. 1995; 10:412-9.

4. Corcos T, Zimarino M, Tamburino C, Favereau X. Randomized trials of direccional atherectomy: implications for clinical practice and future investigation. J Am Coll Cardiol. 1994; 24:431-9.

Figure 90. Coronary artery several weeks following balloon angioplasty. There is distortion and disruption of the atherosclerotic plaque and granulation tissue in a medial
Figure 91. Intramyocardial small artery occluded by foreign body material (? cotton fiber) with an intimal granulomatous and fibrous reaction occluding the vessel (Hematoxylin and Eosin, 20X).

This Page Intentionally Left Blank

Appendix I. Heart Measurements in Adultts (modified from Sunderman FW, Boerner F: Normal values in clinical medicine. Philadelphia. W.B. Saunders Company, 1949).

Mean (cm)

Range (cm)

Thickness, left ventricular muscle

1.5

Thickness, right ventricular muscle

0.5

Thickness, atrial muscle

0.2

Circumference, mitral valve

10

8-10.5

Circumference, aortic valve

7.5

6-7.5

Circumference, pulmonary valve

8.5

7-9

Circumference, tricuspid valve

12

10-12.5

Appendix II. Normal adult laboratory values

BUN mg/dL

3-25

Uric Acid mg/dL

3.5-7.2

Na mEq/L

135-145

T Prot g/dL

5.3-8.0

K mEq/L

3.5-5.0

Albumin g/dL

3.3-5.8

CI mEq/L

98-108

TBili mg/dL

0.1-1.0

C02 mEq/L

20-28

DBili mg/dL

0.2-0.5

Glucose mg/dL

60-100

Alk Phos U/L

50-375

Ca mg/dL

9.0-10.7

SGOT (AST) U/L

1-40

Creat mg/dL

0.1-1.0

SGPT (ALT) U/L

1-45

Lactate nmol/L

0.3-1.3

LD U/L

100-210

Osmolality mOsm/kg

285-295

CK U/L

5-225

Ion Ca mmol/L

1.12-1.23

CK-MB/CK

<2.5%

Mg mg/dL

1.6-2.6

Choi mg/dL

< 197

Phos mg/dL

2.7^4.5

PT sec

9.0-11.5

PTT sec

23.0-34.0

WBC /nL

4.5-13.0

% Gr

40.0-61.5

RBC/pL

4.5-5.3

%Ly

26.7-40.0

Hgb g/dL

13.0-16.0

% Mo

1.0-10.0

Hct vol %

37-49

% Eo

0-3

MCV fL

78-98

% Ba

<2

MCII pg

25-35

Pit n/L

150-440

Appendix III. Abbreviations.

AAA abdominal aortic aneurysm

ABE acute bacterial endocarditis

ABG arterial blood gases

ACh acetylcholine

AChE acetylcholinesterase

AIDS acquired immunodeficiency syndrome

ANA antinuclear antibodies

ARDS adult respiratory distress syndrome

ASA aspirin

ASD atrial septal defect

ATP adenosin triphosphate

AV atrioventricular

BMI body mass index

BP blood pressure

CABG coronary artery bypass graft

CAD coronary artery disease

CCU coronary care unit

CEA carcinoembryonic antigen

CHF congestive heart failure

CK creatin kinase

CM cardiomyopathy

CMV cytomegalovirus

CNS central nervous system

CO cardiac output

COPD chronic obstructive pulmonary disease

CPR cardiopulmonary resuscitation CREST calcinosis, Raynaud's phenomenom, esophageal dysmotility, sclerodactyly and telangiectasia

CSF cerebrospinal fluid

CT computarized tomography

CVA cerebrovascular accident

CXR chest x ray

DCM dilated cardiomyopathy

DIC disseminated intravascular coagulation

DM diaebtes mellitus

ECG electrocardiogram

ECHO enteric cytopathogenic human orphan viruses

EMD electro-mechanical dissociation

ER emergency room

ESR erythrocyte sedimentation rate

FDP

fibrin degradation products

FHC

familial hypertrophic cardiomyopathy

GI

gastrointestinal

H&E

hematoxylin and eosin

HAART

highly active antiretroviral therapy

Hb

hemoglobin

HCM

hypertrophic cardiomyopathy

Hct

hematocrit

HDL

high density lipoproteins

HIV

human immunodeficiency virus

HSV

herpes simplex virus

HTN

hypertension

ICU

intensive care unit

IE

infectious endocarditis

IHD

ischemic heart disease

IM

intramuscular

JVD

jugular venous distension

LA

left atrium

LAD

left anterior descending coronary artery

LAH

left atrium hypertrophy

LCX

left circumflex coronary artery

LDH

lactate deshydrogenase

LDL

low density lipoproteins

LM

left circumflex artery

LV

left ventricle

LVH

left ventricular hypertrophy

MHC

myosin heavy chain

MI

myocardial infarction

MRI

magnetic resonance imaging

MVP

mitral valve prolapse

NE

norepinephrine

NSAID

non-steroidal anti-inflammatory drug

NSR

normal sinus rhythm

PCR

polymerase chain reaction

PCWP

pulmonary capillary wedge pressure

PDA

patent ductus arteriosus

PDA

patent ductus arteriosus

PDGF

platelet-derived growth factor

PPC

peri-partum cardiomyopathy

PPH

plexogenic pulmonary hypertension

PRBC

packed red blood cells

PT

prothrombin time

PTCA

percutaneous transluminal angioplasty

PTT

partial thromboplastin time

PTU

propylthiouracil

PVD

peripheral vascular disease

RA

right atrium

RAH

right atrium hypertrophy

RBBB

right bundle branch block

RCA

right coronary artery

REM

rapid eye movements

RHD

rheumatic heart disease

ROMI

rule out myocardial infarction

RV

right ventricle

RVH

right ventricular hypertrophy

SAM

systolic anterior motion of the mitral valve

SBE

subacute bacterial endocarditis

SCD

sudden cardiac death

SEMI

subendocardial myocardial infarction

SMA

superior mesenteric artery

SVT

supraventricular tachycardia

TA

Takayasu's arteritis

TB

tuberculosis

TEE

transesophageal echocardiogram

TIA

transient ischemic attack

TMMI

transmural myocardial infarction

TMPs

tissue metalloproteinases

TOF

tetralogy of Fallot

TPA

tissue plasminogen activator

TXa

thromboxane

VF

ventricular fibrilation

VSD

ventricular septal defect

WBC

white blood cell count

WPW

Wolf-Parkinson-White

This Page Intentionally Left Blank

Reducing Blood Pressure Naturally

Reducing Blood Pressure Naturally

Do You Suffer From High Blood Pressure? Do You Feel Like This Silent Killer Might Be Stalking You? Have you been diagnosed or pre-hypertension and hypertension? Then JOIN THE CROWD Nearly 1 in 3 adults in the United States suffer from High Blood Pressure and only 1 in 3 adults are actually aware that they have it.

Get My Free Ebook


Post a comment