Pericardial Effusion

 pericardial effusion


Practice Essentials


Pericardial effusion is the presence of an abnormal amount of fluid and/or an abnormal character to fluid in the pericardial space. It can be caused by a variety of local and systemic disorders, or it may be idiopathic. See the image below.


This echocardiogram shows a large amount of pericardial effusion (identified by the white arrows).

Signs and symptoms



Signs and symptoms of pericardial effusion include the following:


· Chest pain, pressure, discomfort


· Light-headedness, syncope


· Palpitations


· Cough


· Dyspnea


· Hoarseness


· Anxiety and confusion


· Hiccoughs


See Clinical Presentation for more detail.


Diagnosis



Examination findings in patients with pericardial effusion include the following:


· Classic Beck triad of pericardial tamponade: Hypotension, muffled heart sounds, jugular venous distention


· Pulsus paradoxus


· Pericardial friction rub


· Tachycardia


· Hepatojugular reflux


· Tachypnea


· Decreased breath sounds


· Ewart sign: Dullness to percussion beneath the angle of left scapula


· Hepatosplenomegaly


· Weakened peripheral pulses, edema, and cyanosis


Lab tests



The following laboratory studies may be performed in patients with suspected pericardial effusion:


· Electrolyte levels


· CBC count with differential


· Cardiac biomarker levels (eg, troponin, CK-MB, LDH)


· Tests for other markers of inflammation (eg, ESR, CRP)


· TSH level


· Blood cultures


· RF levels


· Immunoglobulin complex tests


· ANA tests


· Complement levels


· Pericardial fluid analysis


Early in the course of acute pericarditis, the ECG typically displays diffuse ST elevation in association with PR depression; the ST elevation may be present in all leads except for aVR, although in postmyocardial infarction pericarditis, the changes may be more localized.


Specific tests for infectious diseases or other conditions may also be warranted, based upon clinical suspicion, such as the following:


· Viral cultures


· Tuberculin skin testing or QuantiFERON-TB assay


· Rickettsial antibodies


· HIV serology


· Adenosine deaminase levels


· CEA levels


· PCR


Imaging studies



Echocardiography is the imaging modality of choice for the diagnosis of pericardial effusion and includes the following techniques:


· 2-D echocardiography


· M-mode echocardiography: Adjunct to 2-D echocardiography


· Doppler echocardiography


· Transesophageal echocardiography


· Intracardiac echocardiography


Other radiologic studies used in the evaluation of pericardial effusion include the following:


· Chest radiography


· Chest CT Scanning and MRI: May be superior to echocardiography in detecting loculated pericardial effusions


Procedures



Procedures that may be used in patients with pericardial effusion include the following:


· Diagnostic and/or therapeutic pericardiocentesis


· Diagnostic pericardioscopy


· Placement of a pulmonary artery catheter


See Workup for more detail.


Management



Most acute idiopathic or viral pericarditis occurrences are self-limited and respond to treatment with an NSAID. Colchicine or prednisone may be administered for severe inflammatory pericardial effusions or when NSAID treatment has failed. Colchicine is preferred over steroids (unless specifically indicated), as the latter is associated with an increassed incidence of recurrent pericarditis.


Autoimmune pericardial effusions may respond to treatment with anti-inflammatory medications. In general, selection of an agent depends on the severity of the patient's symptoms and the tolerability and adverse-effect profiles of the medications.


Pharmacotherapy for pericardial effusion includes use of the following agents, depending on the etiology:


· NSAIDs (eg, indomethacin, ibuprofen, naproxen, diclofenac, ketoprofen, aspirin)


· Corticosteroids (eg, prednisone, methylprednisolone, prednisolone)


· Anti-inflammatory agents (eg, colchicine)


· Antibiotics (eg, vancomycin, ceftriaxone, ciprofloxacin, isoniazid, rifampin, pyrazinamide, ethambutol)


· Antineoplastic therapy (eg, systemic chemotherapy, radiation)


· Sclerosing agents (eg, tetracycline, doxycycline, cisplatin, 5-fluorouracil)


Hemodynamic support for pericardial effusion includes the following:


· Hemodynamic monitoring with a balloon flotation pulmonary artery catheter


· IV fluid resuscitation


Surgical treatments for pericardial effusion include the following:


· Pericardiostomy


· Pericardotomy


· Thoracotomy


· Sternotomy


· Pericardiocentesis



Background


Pericardial effusion is the presence of an abnormal amount of and/or an abnormal character to fluid in the pericardial space. It can be caused by a variety of local and systemic disorders, or it may be idiopathic. (See Etiology.)


Pericardial effusions can be acute or chronic, and the time course of development has a great impact on the patient's symptoms. Treatment varies, and is directed at removal of the pericardial fluid and alleviation of the underlying cause, which usually is determined by a combination of fluid analysis and correlation with comorbid illnesses (see the image below). (See Presentation, Workup, Treatment, and Medication.)


This image is from a patient with malignant pericardial effusion. Note the "water-bottle" appearance of the cardiac silhouette in the anteroposterior (AP) chest film.




Embryology



In the human embryo, the pericardial cavity develops from the intraembryonic celom during the fourth week. The pericardial cavity initially communicates with the pleural and peritoneal cavities, but during normal development these are separated by the eighth week.


The visceral and parietal pericardium are derived from the mesoderm, albeit from different parts of the embryo. The visceral pericardium develops from splanchnic mesoderm, as cells originating from the sinus venous spread out over the myocardium. The parietal pericardium derives from lateral mesoderm that covers and accompanies the developing pleuropericardial membrane, which will eventually separate the pleural and pericardial cavities. In healthy subjects, the pericardium covers the heart and great vessels, with the exception of only partially covering the left atrium.


Congenital absence of the pericardium can occur and can be either partial or complete. This condition is often clinically silent, but it can potentially lead to excessive cardiac motion (in the case of complete absence), causing vague chest pain or dyspnea, or, in the case of partial absence with significant defects, strangulation of heart muscle and possible death. [1]


Physiology


The pericardial space normally contains 15-50 mL of fluid, which serves as lubrication for the visceral and parietal layers of the pericardium. This fluid is thought to originate from the visceral pericardium and is essentially an ultrafiltrate of plasma. Total protein levels are generally low; however, the concentration of albumin is increased in pericardial fluid owing to its low molecular weight.


The pericardium and pericardial fluid provide important contributions to cardiac function, including the following:


· The parietal pericardium contributes to resting diastolic pressure, and is responsible for most of this pressure in the right atrium and ventricle


· Through their ability to evenly distribute force across the heart, the pericardial structures assist in ensuring uniform contraction of the myocardium


The normal pericardium can stretch to accommodate a small amount of fluid without a significant change in intrapericardial pressure, although once this pericardial reserve volume is surpassed, the pressure-volume curve becomes steep. With slow increases in volume, however, pericardial compliance can increase to lessen the increase in intrapericardial pressure.


Pathophysiology



Clinical manifestations of pericardial effusion are highly dependent on the rate of accumulation of fluid in the pericardial sac. Rapid accumulation of pericardial fluid may cause elevated intrapericardial pressures with as little as 80 mL of fluid, while slowly progressing effusions can grow to 2 L without symptoms.


Understanding the properties of the pericardium can help to predict changes within the heart under physiologic stress.


By distributing forces across the heart, the pericardium plays a significant role in the physiologic concept of ventricular interdependence, whereby changes in pressure, volume, and function in one ventricle influence the function of the other.


The pericardium plays a pivotal role in cardiac changes during inspiration. Normally, as the right atrium and ventricle fill during inspiration, the pericardium limits the ability of the left-sided chambers to dilate. This contributes to the bowing of the atrial and ventricular septums to the left, which reduces left ventricular (LV) filling volumes and leads to a drop in cardiac output. As intrapericardial pressures rise, as occurs in the development of a pericardial effusion, this effect becomes pronounced, which can lead to a clinically significant fall in stroke volume and eventually progress to the development of pericardial tamponade.


The pericardium plays a beneficial role during hypervolemic states by limiting acute cardiac cavitary dilatation.

Etiology



The cause of abnormal fluid production depends on the underlying etiology, but it is usually secondary to injury or insult to the pericardium (ie, pericarditis). Transudative fluids result from obstruction of fluid drainage, which occurs through lymphatic channels. Exudative fluids occur secondary to inflammatory, infectious, malignant, or autoimmune processes within the pericardium.


In up to 60% of cases, pericardial effusion is related to a known or suspected underlying process. Therefore, the diagnostic approach should give strong consideration to coexisting medical conditions.
Idiopathic


In many cases, the underlying cause is not identified. However, this often relates to the lack of extensive diagnostic evaluation.
Infectious


Human immunodeficiency virus (HIV) infection can lead to pericardial effusion through several mechanisms, including the following:


· Secondary bacterial infection


· Opportunistic infection


· Malignancy (Kaposi sarcoma, lymphoma)


· "Capillary leak" syndrome, which is associated with effusions in other body cavities


The most common cause of infectious pericarditis and myocarditis is viral. Common etiologic organisms include coxsackievirus A and B, and hepatitis viruses. Other forms of infectious pericarditis include the following:


· Pyogenic - Pneumococci, streptococci, staphylococci, Neisseria, Legionella species


· Tuberculous


· Fungal - Histoplasmosis, coccidioidomycosis, Candida


· Syphilitic


· Protozoal


· Parasitic
Neoplastic


Neoplastic disease can involve the pericardium through the following mechanisms:


· Direct extension from mediastinal structures or the cardiac chamber


· Retrograde extension from the lymphatic system


· Hematologic seeding


Malignancies with the highest prevalence of pericardial effusion include lung (37% of malignant effusions) and breast (22%) malignancies, as well as leukemia/lymphoma (17%). However, patients with malignant melanoma or mesothelioma also have a high prevalence of associated pericardial effusions.

Postoperative/postprocedural



Pericardial effusions are common after cardiac surgery. In 122 consecutive patients studied serially before and after cardiac surgery, effusions were present in 103 patients; most appeared by postoperative day 2, reached their maximum size by postoperative day 10, and usually resolved without sequelae within the first postoperative month.


In a retrospective survey of more than 4,500 postoperative patients, only 48 were found to have moderate or large effusions by echocardiography; of those, 36 met diagnostic criteria for tamponade. The use of preoperative anticoagulants, valve surgery, and female sex were associated with a higher prevalence of tamponade. [2]


Early chest tube removal following cardiac surgery, around midnight on the day of surgery, may be associated with an increased risk of postoperative pleural and/or pericardial effusions requiring invasive treatment. [88] This may occur even if chest tube output during the last 4 hours is below 150 mL compared with removal of the tubes next morning.


Symptoms and physical findings of significant postoperative pericardial effusions are frequently nonspecific, and echocardiographic detection and echo-guided pericardiocentesis, when necessary, are safe and effective; prolonged catheter drainage reduces the recurrence rate. [3]


Pericardial effusions in cardiac transplant patients are associated with an increased prevalence of acute rejection. [4]
Other


Less common causes of pericardial effusion include the following:


· Uremia


· Myxedema


· Severe pulmonary hypertension


· Radiation therapy


· Acute myocardial infarction - Including the complication of free wall rupture


· Aortic dissection - Leading to hemorrhagic effusion from leakage into the pericardial sac


· Trauma


· Hyperlipidemia


· Chylopericardium


· Familial Mediterranean fever


· Whipple disease


· Hypersensitivity or autoimmune related -Systemic lupus erythematosus, [5] rheumatoid arthritis, ankylosing spondylitis, rheumatic fever, scleroderma, sarcoidosis, Wegener granulomatosis


· Drug associated - Eg, procainamide, hydralazine, isoniazid, minoxidil, phenytoin, anticoagulants, methysergide

Epidemiology

Occurrence in the United States


Few large studies have characterized the epidemiology of pericardial effusion; however, the available data consistently show that pericardial effusion is more prevalent than is clinically evident. A higher incidence of it is associated with certain diseases.


Small pericardial effusions are often asymptomatic, and pericardial effusion has been found in 3.4% of subjects in general autopsy studies. When associated with community-acquired pneumonia (CAP), small peridcardial effusion is an independent predictor of adverse events including longer and more complicated hospital stays as well as increased mortality. [6]


A wide variety of malignant neoplasms and hematologic malignancies can lead to pericardial effusion. Data on the prevalence varies, with some studies showing the presence of pericardial effusion as high as 21% in such patients. A large study by Bussani et al showed cardiac metastases (9.1%) and pericardial metastases (6.3%) in cases of death from all causes in individuals with an underlying carcinoma at autopsy. [7] As previously mentioned, malignancies with the highest prevalence of pericardial effusion include lung (37% of malignant effusions) and breast (22%) malignancies, as well as leukemia/lymphoma (17%).


Patients with HIV, with or without acquired immunodeficiency syndrome (AIDS), are also found to have an increased prevalence of pericardial effusion. [8] Studies have shown the prevalence of pericardial effusion in these patients to range from 5-43%, depending on the inclusion criteria, with 13% having moderate to severe effusion. The incidence of pericardial effusion in patients infected with HIV has been estimated at 11%; however, it appears that highly active antiretroviral therapy (HAART) may have reduced the incidence of HIV-associated effusions. [9]
Race- and age-related demographics


No consistent difference among races is reported in the literature. AIDS patients with pericardial effusion are more likely to be white.


Pericardial effusion is observed in all age groups. The mean occurrence is in the fourth or fifth decades, although it is earlier than this in patients with HIV.


Pericardial Effusion Clinical Presentation

History



Cardiovascular symptoms in pericardial effusion can include the following:


· Chest pain, pressure, discomfort - Characteristically, pericardial pain may be relieved by sitting up and leaning forward and is intensified by lying supine.


· Light-headedness, syncope


· Palpitations


Respiratory symptoms can include the following:


· Cough


· Dyspnea


· Hoarseness


Neurologic symptoms of pericardial effusion can include anxiety and confusion, while hiccoughs may occur as a gastrointestinal (GI) symptom.

Physical Examination



Cardiovascular findings in pericardial effusion can include the following:


· Classic Beck triad of pericardial tamponade - Hypotension, muffled heart sounds, jugular venous distention


· Pulsus paradoxus - Exaggeration of physiologic respiratory variation in systemic blood pressure, defined as a decrease in systolic blood pressure of more than 10mm Hg with inspiration, signaling falling cardiac output during inspiration


· Pericardial friction rub


· Tachycardia


· Hepatojugular reflux - This can be observed by applying pressure to the periumbilical region; a rise in the jugular venous pressure (JVP) of greater than 3 cm H2 O for more than 30 seconds suggests elevated central venous pressure (however, transient elevation in JVP may be normal)


Pericardial friction rub, the most important physical sign of acute pericarditis, may have up to 3 components per cardiac cycle and is high-pitched, scratching, and grating. It can sometimes be elicited only when firm pressure with the diaphragm of the stethoscope is applied to the chest wall at the left lower sternal border. The pericardial friction rub is heard most frequently during expiration with the patient upright and leaning forward.


Respiratory findings can include the following:


· Tachypnea


· Decreased breath sounds - Secondary to pleural effusions [10]


· Ewart sign - Dullness to percussion beneath the angle of left scapula from compression of the left lung by pericardial fluid


Hepatosplenomegaly represents a GI symptom of pericardial effusion. Findings in the patient’s extremities can include weakened peripheral pulses, edema, and cyanosis.

Differential Diagnoses



· Acute Pericarditis


· Cardiac Tamponade


· Cardiogenic Pulmonary Edema


· Constrictive Pericarditis


· Dilated Cardiomyopathy


· Effusive-Constrictive Pericarditis


· Myocardial Infarction


· Pulmonary Embolism (PE)


Lab Studies



The following lab studies may be performed in patients with suspected pericardial effusion:


· Electrolytes - To assess for metabolic abnormalities (eg, renal failure)


· Complete blood count (CBC) with differential - Leukocytosis for evidence of infection, as well as cytopenias, as signs of underlying chronic disease (eg, cancer, HIV)


· Cardiac biomarkers


· Other markers of inflammation, such as erythrocyte sedimentation rate and C-Reactive protein - While these do not aid in identifying specifics, they can be used to potentially assess the need for anti-inflammatory agents (ie, corticosteroids, colchicine, NSAIDs), especially in the setting of recurrent effusions. [12]


· Thyroid-stimulating hormone - Thyroid-stimulating hormone screen for hypothyroidism [13]


· Blood cultures in the presence of systemic inflammatory response syndrome (SIRS) or fever; in general, specific viral studies are low yield and therefore not recommended [14]


· Rheumatoid factor, immunoglobulin complexes, antinuclear antibody test (ANA), and complement levels (which would be diminished) - In suspected rheumatologic causes


· Specific infectious disease testing, based upon clinical suspicion, such as (1) tuberculin skin testing or QuantiFERON-TB assay; (2) rickettsial antibodies if there is a high index of suspicion for tick-borne disease; and HIV serology
Cardiac enzymes


The troponin level is frequently minimally elevated in acute pericarditis, usually in the absence of an elevated total creatine kinase level. Presumably, this is due to some involvement of the epicardium by the inflammatory process.


Although the elevated troponin may lead to the misdiagnosis of acute pericarditis as a myocardial infarction, most patients with an elevated troponin and acute pericarditis do not have findings at angiography consistent with acute coronary syndrome. An elevated troponin level in acute pericarditis typically returns to normal within 1-2 weeks and is not associated with a worse prognosis.
Pericardial fluid analysis


It should be noted that routine biochemical and cell-count analysis has a low yield in diagnosing the cause of effusion. [15] In contrast, Gram stain and culture can ascertain the etiology convincingly. It is routine for the following tests to be considered part of the standard pericardial fluid analysis:


· Lactic (acid) dehydrogenase (LDH), total protein - The Light criteria (for exudative pleural effusion) found to be as reliable in distinguishing between exudative and transudative effusions: (1) total protein fluid-to-serum ratio >0.5, (2) LDH fluid-to-serum ratio >0.6, (3) LDH fluid level exceeds two thirds of upper limit of normal serum level [16]


· Other indicators suggestive of exudate - Specific gravity >1.015, total protein >3.0 mg/dL, LDH >300 U/dL, glucose fluid-to-serum ratio < 1


· Cell count - Elevated leukocytes (ie, >10,000) with neutrophil predominance suggests bacterial or rheumatic cause, although unreliable


· Gram stain - Specific (but insensitive) indicator of bacterial infection


· Cultures - Signal and identify infectious etiology


· Fluid hematocrit for bloody aspirates - Hemorrhagic fluid hematocrits are usually significantly less than simultaneous peripheral blood hematocrits


· Cytology of pericardial fluid to assess for the presence of malignant cells


Special tests


These studies of the pericardial fluid should be considered individually based on the pretest probability of the suspected coexisting condition. They include the following:


· Viral cultures


· Adenosine deaminase; polymerase chain reaction (PCR); culture for tuberculosis; smear for acid-fast bacilli in suspected tuberculosis infection, especially in patients with HIV


A definite diagnosis of tuberculous pericarditis is based on the demonstration of tubercle bacilli in pericardial fluid or on a histologic section of the pericardium.


Probable tuberculous pericarditis is based on the proof of tuberculosis elsewhere in a patient with otherwise unexplained pericarditis, a lymphocytic pericardial exudate with elevated adenosine deaminase or gamma interferon (IFN) levels, and/or appropriate response to a trial of antituberculosis chemotherapy.


Elevated carcinoembryonic antigen (CEA) levels in pericardial fluid have a high specificity for malignant effusion.


Perform pericardial biopsy, especially if malignant pericardial effusion is suspected. [16] This can be more diagnostic when combined with pericardioscopy.

Chest Radiography



Findings in chest radiography include an enlarged cardiac silhouette (so-called water-bottle heart) and a pericardial fat stripe. One third of patients have a coexisting pleural effusion. Radiography is unreliable in establishing or refuting a diagnosis of pericardial effusion. (See the image below.)


This image is from a patient with malignant pericardial effusion. Note the "water-bottle" appearance of the cardiac silhouette in the anteroposterior (AP) chest film.


Echocardiography



Echocardiography is the imaging modality of choice for the diagnosis of pericardial effusion, as the test can be performed rapidly and in unstable patients. Most importantly, the contribution of pericardial effusion to overall cardiac enlargement and the relative roles of tamponade and myocardial dysfunction in altered hemodynamics can be evaluated with echocardiography.

Patients with viral cardiomyopathy, especially in the acute setting, may have a similar presentation to patients with pericardial effusion, with an enlarged heart being seen on chest radiographs. Echocardiography readily distinguishes the difference between enlarged cardiac chambers and a pericardial effusion.


Two-dimensional echocardiography



Pericardial effusion appears as an echo-free space between the visceral and parietal pericardium. Early effusions tend to accumulate posteriorly owing to expandable posterior/lateral pericardium.


Large effusions are characterized by excessive motion within the pericardial sac, also called swinging. Small effusions have an echo-free space of less than 10 mm and are generally seen posteriorly. Moderate-sized effusions range from 10-20 mm and are circumferential. An echo-free space of more than 20 mm indicates a large effusion. Fluid adjacent to the right atrium is an early sign of pericardial effusion. (See the image below.) [19]


This image is from a patient with malignant pericardial effusion. The effusion is seen as an echo-free region to the right of the left ventricle (LV).


Echocardiography may identify features that suggest hemodynamically significant cardiac tamponade; however, this is a clincial (not echocardiographic) diagnosis. These findings include the following:


· Collapse of the right atrium, especially if it lasts for a third of the cardiac cycle


· Diastolic collapse of the right ventricle


· In hypovolemic patients, the left atrium and left ventricle may also show signs of collapse


Rarely, the cause of the effusion can also be ascertained from echocardiography. The following echocardiographic findings may be helpful:


· Presence of a coagulum in the pericardial space indicating a bloody pericardial effusion (aortic dissection, postoperative, or after other catheter-based procedures)


· Presence of a pacemaker lead either in the vicinity or inside an area of localized effusion, indicating lead perforation as a cause


· Presence of tumor (primary or secondary) in the pericardial space


M-mode echocardiography


M-mode echocardiography is adjunctive to two-dimensional (2-D) imaging for the detection of pericardial effusion. Effusions can be classified using M-mode according to the following system proposed by Horowitz et al :


· Type A - No effusion


· Type B - Separation of epicardium and pericardium


· Type C1 - Systolic and diastolic separation of pericardium


· Type C2 - Systolic and diastolic separation of pericardium, attenuated pericardial motion


· Type D - Pronounced separation of pericardium and epicardium with large echo-free space


In the parasternal long-axis and apical 4-chamber views, discordant changes in right and left ventricular cavity size can suggest pronounced interventricular dependence, also suggesting an echocardiographic “substrate” for tamponade. It is important to note that these changes occur independent of the cardiac cycle (as these are dependent on respiration).


Doppler echocardiography



Transmitral and transtricuspid inflow velocities should be investigated to assess for respiratory variation. Decreases in flow during inspiration (transmitral >25%) or expiration (transtricuspid >40%) should raise the suspicion of clinically significant interventricular dependence and tamponade physiology. However, these findings may be less evident or, in fact, absent in patients on mechanical ventilation, even in the presence of a hemodynamically significant pericardial effusion. [21]


Pulmonic vein inflow may show a decrease in early diastolic flow with hemodynamically significant effusions. Plethoric inferior vena cava with less than 50% collapse during inspiration may indicate elevated right atrial pressures. Hepatic vein diastolic flow reversal seen during expiration is another classic manifestation of ventricular interdependence.


Transesophageal echocardiography



Localized compressive masses, such as postoperative mediastinal hematoma, can cause tamponade without any of the classic 2-dimensional or Doppler manifestations. Transesophageal echocardiography maintains all of the advantages of transthoracic echocardiography and is useful in characterizing loculated effusions. However, this imaging study may be difficult to perform in patients with symptomatic effusions due to hemodynamic instability, with the required sedation being more difficult.


Intracardiac echocardiography



Intracardiac echocardiography (ICE) is generally reserved for the assessment of pericardial effusion in the setting of a percutaneous interventional or electrophysiologic procedure. Phased-array ICE systems can perform 2-D and Doppler interrogations.


False-positive findings



False-positive echocardiographic findings can occur in the presence of pleural effusions, pericardial thickening, increased epicardial fat tissue, atelectasis, and mediastinal lesions. Pericardial cysts, which are usually benign, can be seen classically in the right cardiophrenic angle and can be confused with pericardial effusion.


Epicardial fat tissue is more prominent anteriorly but may appear circumferentially, thus mimicking effusion. Fat is slightly echogenic and tends to move in concert with the heart, 2 characteristics that help to distinguish it from an effusion, which is generally echolucent and motionless. [18, 22, 23]


In patients with pericardial effusion, imaging from low to midposterior thorax can provide additional diagnostic echocardiographic images and should be used in patients in whom conventional images are technically difficult or require additional information.

CT Scanning and MRI


Computed tomography (CT) scanning and magnetic resonance imaging (MRI) may be superior to echocardiography in detecting loculated pericardial effusions, especially when these are located anteriorly. Also, these modalities allow for greater visualization of the thoracic cavity and adjacent structures and therefore may identify abnormalities relating to the cause of the effusion.
CT scanning


CT scanning can potentially determine the composition of fluid and may detect as little as 50mL of fluid. This modality can also detect pericardial calcifications, which can be indicative of constrictive pericarditis.


CT scanning results in fewer false-positive findings than echocardiography. However, it can be problematic in patients who are unstable, given the amount of time required to transport them to and from the scanner and to perform the test.


Certain classic CT signs of tamponade have also been described, such as dilated venae cavae, reflux of contrast into the azygos vein and inferior vena cava, deformity or compression of the cardiac chambers, and bowing of the interventricular septum. [24]
MRI


MRI can detect as little as 30 mL of pericardial fluid. It may be able to distinguish hemorrhagic and nonhemorrhagic fluids, as hemorrhagic fluids have a high signal intensity on T-1 weighted images, whereas nonhemorrhagic fluids have a low signal intensity. Nodularity or irregularity of the pericardium seen on MRI may be indicative of a malignant effusion.


MRI is more difficult to perform acutely than CT scanning is, given the length of time the patient must remain in the scanner.


Late gadolinium enhancement can reveal areas of inflammation, which can potentially help decide about anti-inflammatory therapy in recurrent pericarditis and can also aid in the diagnosis of effusive-constrictive pericarditis.

Electrocardiography



Early in the course of acute pericarditis, the ECG typically displays diffuse ST elevation in association with PR depression (see the image below). The ST elevation is usually present in most leads except for aVR, although in postmyocardial infarction pericarditis, the changes may be more localized. (Patients with uremic pericarditis frequently do not have the typical electrocardiographic abnormalities.)


This electrocardiogram (ECG) is from a patient with malignant pericardial effusion. The ECG shows diffuse low voltage, with a suggestion of electrical alternans in the precordial leads.


Classically, the electrocardiographic changes of acute pericarditis evolve through 4 progressive stages, as follows:


· Stage I - Diffuse ST-segment elevation and PR-segment depression


· Stage II - Normalization of the ST and PR segments


· Stage III - Widespread T-wave inversions: This is important to differentiate from myocardial infarction as T-wave inversions in pericarditis usually occur after ST-segment normalization, unlike myocardial infarction


· Stage IV - Normalization of the T waves


Electrical alternans, which is the beat-to-beat variation in the direction and amplitude of the QRS complex, is the electrical signature of “swinging” of the heart in the pericardial fluid. In extreme cases, it can involve the P as well as the T waves. It is specific, but not sensitive, for tamponade and can also be seen in large pericardial effusions. [26]


Low-voltage QRS complexes, classically defined as total amplitude of the QRS complex less than 0.5 mv in the limb leads and less than 1 mv in the precordial leads, can also be seen in large effusions and tamponade. One study using limb lead criteria showed that it is more specific for tamponade rather than an effusion.

Pericardiocentesis and Pericardioscopy
Pericardiocentesis



This procedure is used for diagnostic as well as therapeutic purposes. Support for the use of echocardiographic guidance is increasing, unless emergent treatment is required. Indications for pericardiocentesis include impending hemodynamic compromise (ie, pericardial tamponade), suspected infectious or neoplastic etiology, and uncertain etiology.
Pericardioscopy


This procedure is not universally available. It may increase diagnostic sensitivity in cases of unexplained pericardial effusions, especially for neoplastic disease. It allows for visualization of pericardium and for pericardial biopsies.

Approach Considerations



Pharmacotherapy for pericardial effusion may include use of the following agents, depending on etiology:


· Aspirin/NSAIDs


· Colchicine


· Steroids


· Antibiotics


Antineoplastic therapy (eg, systemic chemotherapy, radiation) in conjunction with pericardiocentesis has been shown to be effective in reducing recurrences of malignant effusions. Corticosteroids and NSAIDs are helpful in patients with autoimmune conditions.
Pericardial sclerosis


Several pericardial sclerosing agents have been used with varying success rates (eg, tetracycline, doxycycline, cisplatin, 5-fluorouracil). The pericardial catheter may be left in place for repeat instillation if necessary until the effusion resolves.


Complications include intense pain, atrial dysrhythmias, fever, and infection. Success rates are reported to be as high as 91% at 30 days.
Surgery


Surgical treatments for pericardial effusion include the following:


· Pericardiostomy


· Pericardotomy


· Thoracotomy


· Sternotomy


· Pericardiocentesis
Inpatient care


Patients with pericardial effusion who present with significant symptoms or cardiac tamponade require emergent treatment and admission to the intensive care unit (ICU). The pericardial catheter (if placed) should be removed within 24-48 hours to avoid infection. Symptomatic patients should remain hospitalized until definitive treatment is accomplished and/or symptoms have resolved
Outpatient care


Patients should be educated with regard to symptoms of increasing pericardial effusion and should be evaluated whenever these symptoms begin to occur. Indications for echocardiography after diagnosis include the following:


· A follow-up imaging study to evaluate for recurrence/constriction - Repeat studies may be performed to answer specific clinical questions.


· The presence of large or rapidly accumulating effusions - To detect early signs of tamponade
Transfer


Symptomatic patients requiring treatment (who are surgical candidates) should receive care at an institution with cardiothoracic surgery capabilities.

Consultations



A cardiologist should be involved in the care of patients with pericardial effusion. Cardiothoracic surgery may be required for recurrent or complicated cases.

Aspirin/NSAIDs


Most acute idiopathic or viral pericarditis occurrences are self-limited and respond to treatment with aspirin (650 mg q6h) or another NSAID. For idiopathic or viral pericarditis, ibuprofen is preferred, given its low adverse effect profile, favorable impact on the coronary blood flow, and large dose range. Based on severity and response, the dose can range from 300-800 mg every 6-8 hours. [28]


Aspirin may be the preferred nonsteroidal agent to treat pericarditis after myocardial infarction because other NSAIDs may interfere with myocardial healing. Indomethacin should be avoided in patients who may have coronary artery disease.


In a study of 196 patients at high risk for tamponade because of pericardial effusion more than 7 days after cardiac surgery, Meurin et al found that diclofenac was not effective in reducing the size of the effusion or in preventing late cardiac tamponade. In the multicenter, randomized, double-blind trial, patients received either diclofenac (50 mg) or placebo twice daily for 14 days.


Colchicine


The routine use of colchicine in combination with conventional therapy is supported by results from the COlchicine for acute PEricarditis (COPE) trial. In this study, 120 patients with a first episode of acute pericarditis (idiopathic, acute, postpericardiotomy syndrome, or connective tissue disease) entered a randomized, open-label trial comparing aspirin treatment alone with aspirin plus colchicine (1-2 mg for the first day followed by 0.5-1 mg daily for 3 mo). [30]


In the study, colchicine reduced symptoms at 72 hours (11.7% vs 36.7) and reduced recurrence at 18 months (10.7% vs 36.7%). Colchicine was discontinued in 5 patients because of diarrhea, but no other adverse events were noted. Importantly, none of the 120 patients developed cardiac tamponade or progressed to pericardial constriction. The ICAP Trial (Investigation on Colchicine for Acute Pericarditis) will provide further information regarding the use of colchicine as first-line therapy. [31]


However, colchine may not be effective for patients with asymptomatic postoperative pericardial effusion. A study involving 149 patients with mild or moderate pericardial effusion on transthoracic echocardiography found no significant difference on pretreatment and posttreatment effusion values and changes in isolated coronary artery bypass graft surgery patients who received colchicine (n = 74) and those who received placebo (n = 75). [89] The investigators attributed these findings to the likelihood that most of the cases of pericardial effusion were from noninflammatory causes

Steroids


Steroid administration early in the course of acute pericarditis appears to be associated with an increased incidence of relapse after the steroids are tapered. In the COPE trial, steroid use was an independent risk factor for recurrence. Also, an observational study strongly suggested that the use of steroids increases the probability of relapse in patients treated with colchicine. [30]


Systemic steroids should be considered only in patients with recurrent pericarditis that is unresponsive to NSAIDs and colchicine or as needed for treatment of an underlying inflammatory disease. If steroids are to be used, an effective dose (1-1.5 mg/kg of prednisone) should be given, and it should be continued for at least 1 month before slow tapering. The European Society of Cardiology recommends that systemic corticosteroid therapy be restricted to connective-tissue diseases, autoreactive pericarditis, or uremic pericarditis. [28]


The intrapericardial administration of steroids has been reported to be effective in acute pericarditis without producing the frequent reoccurrence of pericarditis that complicates the use of systemic steroids, [32] but the invasive nature of this procedure limits its use.

Antibiotics

Purulent pericarditis


In patients with purulent pericarditis, urgent pericardial drainage combined with intravenous (IV) antibacterial therapy (eg, vancomycin 1 g bid, ceftriaxone 1-2 g bid, and ciprofloxacin 400 mg daily) is mandatory. Irrigation with urokinase or streptokinase, using large catheters, may liquify the purulent exudate, but open surgical drainage is preferable.
Tuberculous pericarditis


The initial treatment of tuberculous pericarditis should include isoniazid 300 mg daily, rifampin 600 mg daily, pyrazinamide 15-30 mg/kg daily, and ethambutol 15-25 mg/kg daily. Prednisone 1-2 mg/kg daily is given for 5-7 days and progressively reduced to discontinuation in 6-8 weeks. Drug sensitivity testing is essential. Uncertainty remains whether adjunctive corticosteroids are effective in reducing mortality or progression to constriction.


Surgical resection of the pericardium remains the appropriate treatment for constrictive pericarditis. The timing of surgical intervention is controversial, but many experts recommend a trial of medical therapy for noncalcific pericardial constriction and pericardiectomy in nonresponders after 4-8 weeks of antituberculosis chemotherapy.

Hemodynamic Support



Patients who have an effusion with actual or threatened tamponade should be considered to have a true or potential emergency. Most patients require pericardiocentesis to treat or prevent tamponade. However, treatment should be carefully individualized.


Hemodynamic monitoring with a balloon flotation pulmonary artery catheter is useful, especially in patients with tamponade or threatened tamponade in whom a decision is made to defer pericardiocentesis. Hemodynamic monitoring is also helpful after pericardiocentesis to assess reaccumulation and the presence of underlying constrictive disease. However, insertion of a pulmonary artery catheter should not be allowed to delay definitive therapy in critically ill patients.


IV fluid resuscitation may be helpful in cases of hemodynamic compromise. In patients with tamponade who are critically ill, IV positive inotropes (dobutamine, dopamine) can be used but are of limited use and should not be allowed to substitute for or delay pericardiocentesis.


Pericardiocentesis

As previously mentioned, pericardiocentesis is used for diagnostic as well as therapeutic purposes. Pericardial fluid drainage can be performed by percutaneous catheter drainage or open surgical approach. Individual patient characteristics (eg, loculated vs circumferential, recurrent pericardial effusion, need for pericardial biopsy and location of pericardial effusion) and local practice patterns aid in deciding the optimal method of drainage.


Percutaneous pericardial fluid drainage (pericardiocentesis) is the most common method used for pericardial fluid removal. It can be performed under fluoroscopic, echocardiographic, or CT guidance.


Echocardiographic pericardial fluid drainage has established itself as the criterion standard technique. In study of 1127 procedures performed on 977 patients, echocardiographic-guided pericardiocentesis was successful in 97%, with 1.2% major and 3.5% minor complications. [33] It also established the extended drainage as a means to reduce the recurrence rate.


Use of a needle that is at least 5cm long and 16-gauge in diameter and that has a short bevel can minimize the risk of complications and should allow for adequate pericardial drainage. A system allowing placement of a catheter over the needle is preferred.


Contrast echocardiography using agitated saline is useful in cases in which bloody fluid is aspirated, to determine if the needle is in the ventricular cavity.


Attaching an ECG electrode to the pericardiocentesis needle is also useful for avoiding myocardial puncture. Electrical activity will be seen on the monitor when the needle comes into contact with atrial or ventricular myocardium. These changes may be delayed, however, and instill a false sense of security in needle placement. Sense of touch and the findings on aspiration should guide the procedure, with the clinician ultimately relying on good clinical sense.


Complications of pericardiocentesis include ventricular rupture, dysrhythmias, pneumothorax, myocardial and/or coronary artery laceration, and infection. Recurrence rates for pericardial effusion within 90 days may be as high as 90% in patients with cancer.


Pericardiotomy and Pericardiostomy

Balloon pericardotomy



In this procedure, a catheter is placed in the pericardial space under fluoroscopy. Inflation of the balloon creates a channel for passage of fluid into the pleural space, where reabsorption occurs more readily. Balloon pericardiotomy may be useful for recurrent effusions.
CT-guided pericardiostomy


Patients with effusions after cardiothoracic surgery often have limited echocardiographic windows, as well as loculated effusions, and may be on continued ventilatory support, all of which increase the difficulty of echo-guided pericardiocentesis.


CT pericardial fluid drainage has evolved as an emerging technique suited to overcome this dilemma. It has been shown as an alternative technique in patients in whom fluoroscopically or echocardiographically guided pericardiocentesis is difficult. Echocardiography can be limited due to various patient characteristics (eg, postoperative state, obesity, or chronic obstructive pulmonary disease) or due to a limitation of echocardiography in differentiating pericardial fluid from other possible surrounding structures.


In one large series, CT-directed diagnostic and therapeutic pericardiocentesis was attempted in 261 patients, with 98.4% success, 0.3% major complications and 6.9% minor complications. [34]


In 2010, Eichler et al reported their data on CT-guided pericardiocentesis in 20 patients who were poor candidates for echocardiographic drainage or pericardial fluid was not well visualized by echocardiography. All patients had successful drainage, with 0% mortality and no major complications. [35]


A report by Palmer et al suggested that, in postsurgical cases, CT-guided pericardial drainage is both safe and cost effective. The authors reported on 36 patients—33 of whom underwent major cardiothoracic surgery and 3 of whom were treated with minimally invasive procedures—whose symptomatic pericardial effusions were drained using CT-guided percutaneous placement of an indwelling pericardial catheter. [36]


There were no clinically significant complications associated with any of the placement procedures. Thirty-three patients experienced no symptom recurrence following catheter removal, although pericardial effusion did recur in the remaining 3 patients, requiring a repeat treatment.


Comparing procedure costs, the authors determined that the CT-guided tube pericardiostomies cost 89% less than intraoperative pericardial window procedures would have. No significant procedure-cost differences were found between CT-guided and ultrasonographically guided tube pericardiostomies.


Subxiphoid Pericardial Window With Pericardiostomy



This procedure is associated with low morbidity, mortality, and recurrence rates, and can be considered as a reasonable alternative diagnostic or treatment modality to pericardiocentesis in selected patients. [37]


The surgery can be performed under local anesthesia. This is advantageous because general anesthesia often leads to decreased sympathetic tone, resulting in hemodynamic collapse in patients with pericardial tamponade and shock. This procedure may be less effective when effusion is loculated.


One study indicated that the procedure may be safer and more effective at reducing recurrence rates than pericardiocentesis. However, only patients who were hemodynamically unstable underwent pericardiocentesis, and no change in overall survival rate was observed.

Thoracotomy and Median Sternotomy

Thoracotomy


This procedure should be reserved for patients in whom conservative approaches have failed. Thoracotomy allows for creation of a pleuropericardial window, which provides greater visualization of the pericardium. Thoracotomy requires general anesthesia and thus has higher morbidity and mortality rates than does the subxiphoid approach.
Median sternotomy


This procedure is reserved for patients with constrictive pericarditis. The operative mortality rate is high (5-15%).

Video-Assisted Thoracic Surgery



Video-assisted thoracic surgery (VATS) allows resection of a wider area of the pericardium than the subxiphoid approach does, without the morbidity of thoracotomy. [38] The surgeon is able to create a pleuropericardial window and address concomitant pleural pathology, which is especially common in patients with malignant effusions.


One disadvantage of VATS is that it requires general anesthesia with single lung ventilation, which may be difficult in otherwise seriously ill patients.


Pericardial Effusion Medication

Medication Summary


Most acute idiopathic or viral pericarditis occurrences are self-limited and respond to treatment with an NSAID. The corticosteroid prednisone may be administered for severe inflammatory pericardial effusions or when NSAID treatment has failed.


Research indicates that the anti-inflammatory drug colchicine, when used in combination with conventional therapy, is more effective at reducing the symptoms and recurrence of pericarditis than is conventional therapy alone. [30]


Autoimmune pericardial effusions may respond to treatment with anti-inflammatory medications. In general, selection of an agent depends on the severity of the patient's symptoms and the tolerability and adverse effect profiles of the medications.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)


Class Summary


These agents are used mostly for patients with active, nonhemorrhagic pericarditis with or without pericardial effusion. NSAIDS have analgesic, anti-inflammatory, and antipyretic activities.


The mechanism of action in pericarditis is not known, but NSAIDS may inhibit cyclo-oxygenase activity and prostaglandin synthesis. Other mechanisms may exist as well, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell-membrane functions.



Indomethacin (Indocin)



Indomethacin is the drug of choice in this class, although other NSAIDs (ie, ibuprofen, naproxen, aspirin) possess some efficacy. It is used as initial therapy for mild to moderately severe inflammatory pericardial effusions.



Ibuprofen (Advil, Motrin, Addaprin, Ultraprin)



Ibuprofen is a propionic acid derivative that reduces the formation of inflammatory mediators by enzyme inhibition.


Naproxen (Aleve, Anaprox, Naprosyn, Naprelan)


Naproxen is a propionic acid derivative that reduces the formation of inflammatory mediators by enzyme inhibition.

Diclofenac sodium (Cataflam, Voltaren SR, Zipsor)




Diclofenac possesses properties similar to those of the propionic acid derivatives and reduces the formation of inflammatory mediators by enzyme inhibition. The tablets are immediate-release formulations.


Ketoprofen


Ketoprofen is used for relief of mild to moderate pain and inflammation. Small dosages are indicated initially in small patients, elderly patients, and patients with renal or liver disease. Doses higher than 75 mg do not increase the therapeutic effects. Administer high doses with caution, and closely observe the patient's response.

Aspirin (Bayer Aspirin, Ascriptin, Bufferin, Ecotrin)



Aspirin inhibits prostaglandin synthesis, preventing the formation of platelet-aggregating thromboxane A2.


Corticosteroids


Class Summary


Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. These agents modify the body's immune response to diverse stimuli.


Prednisone



Prednisone is used for patients with severe inflammatory pericardial effusions or for those in whom initial treatment with NSAIDs has failed. Other agents may be used if the adverse effect profile warrants; dosages should be determined by prednisone equivalents.


Methylprednisolone (Solu-Medrol, Depo-Medrol, A-Methapred)


Methylprednisolone is available in IV/IM and oral form. It decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing increased capillary permeability. It is used for patients with severe inflammatory pericardial effusions or for those in whom initial treatment with NSAIDs has failed.


Prednisolone (Pediapred, Prelone, Orapred, Millipred)



Prednisolone is available in IV/IM and oral form. It decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing increased capillary permeability. It is used for patients with severe inflammatory pericardial effusions or for those in whom initial treatment with NSAIDs has failed


Anti-inflammatory Agents



Class Summary


These agents inhibit key factors involved in inflammatory reactions.


Colchicine


Colchicine is an alkaloid extract that inhibits microtubule formation and has unique anti-inflammatory properties. The drug concentrates well in leukocytes and reduces neutrophilic chemotaxis and motility. Colchicine reduces the release of lactic acid and proinflammatory enzymes. It inhibits the release of histamine-containing granules from mast cells, which may be important in the pathogenesis of elastic tissue changes found in anetoderma.


The use of colchicine in autoimmune disease is primarily empiric, and the mechanism of action in the reduction of inflammation is not clear. Colchicine is not truly an immunomodulating agent.

Postinfarction Ventricular Septal Rupture


Postinfarction Ventricular Septal Rupture


Practice Essentials


Ventricular septal rupture (VSR) is a rare but lethal complication of myocardial infarction (MI). The event occurs 2-8 days after an infarction and often precipitates cardiogenic shock. [1] The differential diagnosis of postinfarction cardiogenic shock should exclude free ventricular wall rupture and rupture of the papillary muscles.


Ventricular septal defect (VSD) is defect in interventricular septum (wall dividing left and right ventricles of heart).



To avoid the high morbidity and mortality associated with this disorder, patients should undergo emergency surgical treatment. [2, 3, 4, 5] In current practice, postinfarction VSR is recognized as a surgical emergency, and the presence of cardiogenic shock is an indication for intervention. [6] Long-term survival can be achieved in patients who undergo prompt surgery. Concomitant coronary artery bypass grafting (CABG) may be required. The addition of CABG has helped improve long-term survival.


Surgery is performed via a transinfarction approach, and all reconstruction is performed with prosthetic materials to avoid tension. Developments in myocardial protection and improved prosthetic materials have contributed greatly to successful management of VSR. [7] Improved surgical techniques (eg, infarctectomy) and better perioperative mechanical and pharmacologic support have helped lower mortality. In addition, the development of surgical techniques to repair perforations in different areas of the septum has led to improved results.


In current practice, patients undergoing shunt repair tend to be older and are more likely to have received thrombolytic agents, which may complicate repair. After successful repair, survival and quality of life are excellent, even in patients older than 70 years. [8]


For information, news, and CME activities on heart failure, see the Heart Failure Resource Center. For patient education resources, see the Heart Center, as well as Ventricular Septal Defect and Heart Attack.

Pathophysiology


The septal blood supply comes from branches of the left anterior descending coronary artery, the posterior descending branch of the right coronary artery, or the circumflex artery when it is dominant. Infarction associated with a VSR is usually transmural and extensive. About 60% of VSRs occur with infarction of the anterior wall, 40% with infarction of the posterior or inferior wall (see the image below). Posterior VSR may be accompanied by mitral valve insufficiency secondary to papillary muscle infarction or dysfunction.


Heart sectioned transversely at level of middle left ventricle. Posterior ventricular septal defect is visible at site of recent acute myocardial infarction.



At autopsy, patients with VSR usually show complete coronary artery occlusion with little or no collateral flow. The lack of collateral flow may be secondary to associated arterial disease, anatomic anomalies, or myocardial edema. Sometimes, multiple septal perforations occur. These may occur simultaneously or within several days of each other.


Ventricular aneurysms are commonly associated with postinfarction VSR and contribute significantly to the hemodynamic compromise in these patients. The reported incidence of ventricular aneurysms ranges from 35% to 68%, whereas the incidence of ventricular aneurysms alone after MI without VSR is considerably lower (12.4%).


The natural history of postinfarction VSR is greatly influenced by hypertension, anticoagulation therapy, advanced age, and, possibly, thrombolytic therapy. The natural course in patients with postinfarction VSR is well documented and short. Most patients die within the first week, and almost 90% die within the first year; some reports indicate that fewer than 7% of patients are alive after 1 year.


This grim prognosis results from an acute volume overload exacted on both ventricles in a heart already compromised by a large MI and occasionally by extensive coronary artery disease (CAD) in sites other than that already infarcted. In addition, superimposed ischemic mitral valve regurgitation, a ventricular aneurysm, or a combination of these conditions may be present, further compromising heart function. The depressed left ventricular function commonly leads to impaired peripheral organ perfusion and death in most patients.


A few sporadic reports indicate that some patients with medically treated postinfarction VSR live for several years. Although many medical advances have been made in the nonsurgical treatment of these patients, including intra-aortic balloon counterpulsation (IABCP), these methods have not eliminated the need for surgery.



Epidemiology



Rupture of the interventricular septum is an uncommon complication of MI. Although autopsy studies reveal an 11% incidence of myocardial free-wall rupture after MI, septal-wall perforation is much less common, occurring at a rate of approximately 1-2%.


VSR occurs in a zone of necrotic myocardial tissue, usually within the first 10-14 days. Clinical studies report an average time of 2.6 days from MI to VSR. However, some data suggest that initial treatment of MI with thrombolytics may affect both the time between infarction and VSR and the eventual outcome. Early use of thrombolytic agents may lead to reopening of the occluded vessels, thereby reducing the incidence of VSR.


The age range of patients who sustain a postinfarction VSR is wide, from 44 to 81 years. Men are affected more commonly than women are, though VSR is more common in women than would be predicted on the basis of the prevalence of CAD alone.

Prognosis



Operative mortality is directly related to the interval between MI and surgical repair. In a retrospective analysis of 41 patients treated for postinfarction ventricular septal defect (VSD), Serpytis et al confirmed that whereas female sex, advanced age, arterial hypertension, anterior-wall acute MI, absence of previous acute MI, and late arrival at hospital were associated with a higher risk of mortality from acute VSD, the time from the onset of acute MI to operation was the most important factor determining operative mortality and intrahospital survival. [9]


If repair of a postinfarction VSR is performed 3 weeks or more after the infarction, mortality is approximately 20%; if it is performed before this time, mortality approaches 50%. The most obvious reason for this is that the greater the degree of myocardial damage and hemodynamic compromise, the more urgent the need for early intervention.


With the use of an early operative approach, most studies show an overall mortality of less than 25%. Mortality tends to be lower for patients with anteriorly located VSRs and lowest for patients with apical VSRs. For anterior defects, mortality ranges from 10% to 15%; for posterior defects, mortality ranges from 30% to 35%.


More than 50% of deaths occurring after surgery for postinfarction VSR are due to cardiac failure. Sudden death is rare, and intractable heart failure can also occur. Other causes of death include cerebral embolism. Most patients who survive the hospital period have good functional status, with the majority falling into New York Heart Association (NYHA) class I or II. [10]


The most important risk factors for death in the early phase are poor hemodynamics and associated right ventricular dysfunction developing before the patient comes to the operating room. The amount and distribution of myocardial necrosis and scarring are responsible for both.


Right ventricular dysfunction results from ischemic damage or frank infarction of the right ventricle and is present when stenosis occurs in the right coronary artery system. The higher mortality observed after repair of defects located inferiorly in the septum is probably related to the higher prevalence of important right coronary artery stenosis.


The severity and distribution of CAD are also risk factors. Similarly, advanced age at operation, diabetes, and preinfarction hypertension are risk factors for death in the early phase.


Risk factors for death in patients with postinfarction VSR may be summarized as follows:



  • · Posteriorly located VSRs are technically more difficult to repair and are associated with profound right ventricular dysfunction
  • · The presence of multiple organ failure is a poor prognostic factor
  • · The presence of cardiogenic shock does not bode well for the patient’s survival
  • · A shortened interval between infarction and surgery usually indicates that the patient is considered more ill and therefore is at greater risk for death



In a retrospective analysis of 52 consecutive patients with surgically repaired postinfarction VSR over a 30-year period (mean follow-up, 7.8±7.7 years), Takahashi et al found that predictors of 30-day mortality on univariate analysis included the following :



  • · Renal insufficiency
  • · Shock at surgery
  • · Emergency surgery
  • · Logistic EuroSCORE
  • · Three-vessel disease
  • · Significant left circumflex coronary arterial stenosis
  • · Significant right coronary arterial stenosis
  • · Incomplete revascularization
  • · Surgical duration
  • · Cardiopulmonary bypass time



On multivariate analysis, only incomplete coronary revascularization was an independent risk factor for 30-day mortality


History and Physical Examination



Upon auscultation, a loud systolic murmur is heard, usually within the first week after an acute myocardial infarction (MI). This is the most consistent physical finding of postinfarction ventricular septal rupture (VSR). Before the development of the murmur, the patient may have been stable after the acute MI. Coincident with the onset of the murmur, the patient’s clinical course undergoes a sudden deterioration, with the development of congestive heart failure (CHF) and, often, cardiogenic shock.


The typical harsh systolic murmur is audible over a large area, including the left sternal border and apical area. It sometimes radiates to the left axilla, thereby mimicking mitral regurgitation (MR). A thrill is palpable in approximately 50% of patients.


Almost 50% of patients have recurrent chest pain. The differential diagnosis includes VSR and mitral insufficiency secondary to papillary muscle rupture, papillary muscle dysfunction, or left ventricular dilatation.


Clinical features of VSR may be summarized as follows:

  • · The rupture typically occurs 3-8 days after an MI
  • · VSR is more likely to occur in the anterior septum than in the posterior septum (60% vs 40%)
  • · The most consistent finding is a murmur
  • · In the differential diagnosis, exclude MR from papillary muscle rupture
  • · Diagnosis is confirmed with the aid of echocardiography and the presence of a left-to-right shunt
  • · Catheterization results help determine the extent of coronary artery disease (CAD)
  • · Of patients treated without surgery, 90% die
  • · Surgical treatment must be carried out on an emergency basis, even if the patient is stable [3]
  • · All VSRs are closed with a patch and associated coronary artery bypass grafting (CABG)
  • · Operative mortality is 10-15% for anterior defects and 30-35% for posterior defects




Imaging Studies



On plain chest radiography, 82% of patients with postinfarction ventricular septal rupture (VSR) demonstrate left ventricular enlargement, 78% have pulmonary edema, and 64% have a pleural effusion. These findings are nonspecific and do not exclude other causes, such as a ruptured papillary muscle.


M-mode transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) have been used to help diagnose postinfarction VSR. TTE findings have been improved with the use of color-flow Doppler methods to visualize the VSR. In addition, echocardiography can help assess the presence of any mitral valve pathology. (See the image below.)


Ventricular septal defect on echocardiography.


Electrocardiography



No electrocardiographic (ECG) features are diagnostic of postinfarction VSR, though ECG indeed provides some useful information. Persistent ST-segment elevation associated with ventricular aneurysm is common. ECG may reveal atrioventricular block in one third of patients. ECG can also be used to help predict the anatomic location of the septal rupture. (See the image below.)


Acute anterior myocardial infarction on ECG.


Catheterization and Pressure Measurement


Left-heart catheterization with coronary angiography is recommended in all stable patients. This procedure is time-consuming and carries some degree of morbidity in already compromised patients; accordingly, good judgment is required when this test is ordered.


An important diagnostic test for differentiating VSR from mitral valve insufficiency is catheterization of the right heart with a Swan-Ganz catheter. In the presence of a VSR, oxygen concentration between the right atrium and the pulmonary artery is stepped up. In addition, a pulmonary capillary wedge pressure tracing is beneficial for differentiating acute mitral regurgitation (MR) from VSR.


Left- and right-side pressure measurements help estimate the degree of biventricular failure and are useful in monitoring the response to perioperative therapy. Whereas right-side failure is more common in patients with postinfarction VSR, left-side failure and refractory pulmonary edema are more prominent in patients with a ruptured papillary muscle. However, one third of patients with postinfarction VSR also have some degree of MR secondary to left ventricular dysfunction. Only rarely is VSR also associated with ruptured papillary muscle.




Medical Therapy



Initiate pharmacologic therapy in an attempt to render the patient hemodynamically stable. The goals are to reduce afterload on the heart and to increase forward cardiac output.


Vasodilators may be used in an attempt to decrease the left-to-right shunt associated with the mechanical defect and thereby increase cardiac output. Intravenous (IV) nitroglycerin can be used as a vasodilator and may provide improved myocardial blood flow in patients with significant ischemic cardiac disease.


When used alone, inotropic agents may increase cardiac output; however, without changes in the ratio of pulmonary to systemic flow (Qp-to-Qs ratio), they markedly increase left ventricular work and myocardial oxygen consumption. The profound level of cardiogenic shock in some patients precludes vasodilator treatment, often necessitating vasopressor support.


Vasopressors markedly increase left ventricular work and myocardial oxygen consumption. They also increase systemic afterload and further increase the Qp-to-Qs ratio, thus lowering cardiac output and greatly augmenting myocardial oxygen consumption.


Intra-aortic balloon counterpulsation (IABCP) offers the most important means of temporary hemodynamic support. IABCP reduces left ventricular afterload, thus increasing systemic cardiac output and decreasing the Qp-to-Qs ratio. IABCP also facilitates diastolic augmentation with an increase in coronary blood flow, resulting in an improved oxygen supply.


IABCP is not a substitute for urgent intervention, and in patients with cardiogenic shock, it should be followed by immediate intervention. Patients with ventricular septal rupture (VSR) do not die of cardiac failure; they die as a result of end-organ failure. Only by shortening the duration of shock can the high risk of mortality be prevented.


Achieving hemodynamic stability before surgery is very beneficial, but prolonged attempts to improve the patient’s hemodynamic status can be hazardous. [12]


This aggressive approach often results in temporary stability of these extremely ill patients. As a rule, however, these benefits are brief, and patients may deteriorate rapidly. Therefore, early diagnosis and rapid surgical intervention should be planned. Only about 10-15% of patients can be treated with conservative measures for a period of 2-4 weeks, after which surgical treatment can be provided at a greatly reduced risk.


Surgical Therapy


Indications and contraindications


In view of the grim prognosis for medically treated patients, the diagnosis of postinfarction VSR, by itself, constitutes an indication for operation. The controversy that once surrounded the timing of surgical intervention is no longer an issue, and most surgeons now agree that early surgery is indicated to minimize the risk of mortality and morbidity. The success of surgical therapy depends on prompt medical stabilization of the patient and prevention of cardiogenic shock.


The relative safety of repair 2-3 weeks or more after perforation has been established. Because the edges of the defect have become firmer and fibrotic, repair is more secure and is easily accomplished. A successful clinical outcome is related to the adequacy of the closure of the VSR; therefore, if possible, search for multiple defects both preoperatively and at the time of surgery.


Only when the patient is hemodynamically stable should repair be initially delayed, but there must be a high degree of certainty that the patient is in fact stable. These patients can suddenly deteriorate and die. The criteria for a delay in surgical treatment include the following:


· Adequate cardiac output


· No evidence of cardiogenic shock


· Absence of signs and symptoms of congestive heart failure (CHF) or minimal use of pressor agents to control initial symptoms


· Absence of fluid retention


· Good renal function


The natural history of the disease is such that few patients present with these signs and symptoms. In most patients, postinfarction VSR rapidly leads to a worsening of the hemodynamic state, with cardiogenic shock, marked and intractable symptoms of CHF, and fluid retention. Immediate surgery is usually indicated. [6] The high surgical risk of early repair is accepted because of the even higher risk of death without surgery under such circumstances.


Occasionally, a delay in diagnosis and referral occurs. These patients are usually critically ill, and the prognosis is very grim; thus, allowing the natural history of the disease to take its course is prudent. [6]


Although most patients who experience postinfarction VSR need emergency surgery, an occasional patient, because a delay in either diagnosis or referral, may be in a state of multiorgan failure and may not be a candidate for surgery. The chances of such a patient surviving an operation are minimal; in these circumstances, supportive medical therapy may be adequate. [6] Patients who are comatose and in cardiogenic shock have a particularly poor prognosis after surgery, and surgery is best avoided in such circumstances.


Choice of operative approach



The first operations for repair of postinfarction VSR used an approach through the right ventricle, with an incision of the right ventricular outflow tract such as was used to repair some congenital ventriculoseptal defects (VSDs). This approach proved inadequate because of limited exposure for lesions at the apex of the heart, injury to normal right ventricular muscle, interruption of coronary collateral vessels, and failure to excise the infarcted tissue.


Subsequently, a transinfarction approach was described, which incorporated infarctectomy, aneurysmectomy, and repair of the ventricular septal perforation. Several techniques have been used to close these defects. The choice of procedure is determined by the location of the defect.


Most defects are anteroapical and are closed by buttressing the defect with viable muscle from the adjacent anterior left ventricular wall. Smaller defects located high in the ventricular septum are closed with a Dacron patch.


High posterior septal or inferior defects, which are less common, are approached through the inferior portion of the heart, usually in the distribution of the posterior descending coronary branch of the right coronary artery. The incision is made in the area of maximal infarction, which is usually on the right ventricular side of the septum. A well-proven principle of repair for these defects is the use of a synthetic patch closure to prevent tension.


A triple-patch approach has been described, with acceptable early and midterm outcomes.


Additional procedures that may be considered in the treatment of postinfarction VSR include the following:


· Concomitant coronary artery bypass grafting (CABG)


· Mitral valve replacement


· Excision of left ventricular aneurysm


Controversy surrounds the issue of whether to perform CABG in patients undergoing emergency postinfarction VSR repair. Some authors have found no benefit to CABG in this setting and have concluded that cardiac catheterization in ill patients is time-consuming and poses a risk of contrast injury to the kidney. Others, however, have used a selective approach to cardiac catheterization.


In patients who probably do not have a history of angina or previous myocardial infarction (MI), cardiac catheterization is deferred. Cardiac catheterization findings help confirm and quantitate the presence of a shunt and reveal pulmonary artery pressure and resistance values. The left ventriculogram helps in determining the location and number of VSDs, defining left ventricular function, and assessing mitral valve function. Most surgeons perform bypass in patients with VSR, with significant improvements in survival.


Occasionally, significant mitral regurgitation (MR) may be associated with acute VSR, particularly when the infarction is posterior. In such circumstances, the mitral valve must be replaced. Replacement is usually best accomplished through the left ventriculotomy by using interrupted, pledgeted mattress sutures.


When a left ventricular aneurysm is associated with postinfarction VSR, it is excised as the initial step in surgical therapy. After repair of the VSR, the aneurysm is generally repaired.


Preparation for surgery



Preoperative management is directed toward rapid resuscitation and stabilization of the patient and preparation for surgery. The goals are as follows:


· To reduce systemic vascular resistance (thereby decreasing the left-to-right shunt)


· To maintain a stable cardiac output and blood pressure


· To maintain coronary artery blood flow


Preoperative treatment of patients with postinfarction VSR may be summarized as follows:


· Transfer patients to an intensive care unit (ICU) for resuscitation


· Place a Swan-Ganz catheter to assist with hemodynamic management


· Decrease the systemic vascular resistance and the left-to-right shunt with vasodilators


· Maintain cardiac output and organ perfusion with inotropic agents


· Maintain coronary artery blood flow


· Use IABCP to decrease myocardial oxygen consumption, decrease afterload, and increase coronary artery perfusion


· Use mechanical ventilation as required


· Use echocardiography to help determine the site of septal rupture


· Use cardiac catheterization to help determine the presence of coronary artery disease (CAD)


Closure of defect



Principles associated with the evolution of techniques for the closure of postinfarction VSR may be summarized as follows:



  • · Determine and understand the anatomy and location of the VSR and any associated coronary artery pathology
  • · Expeditiously establish hypothermic total cardiopulmonary bypass, and pay attention to myocardial protection with cardioplegia
  • · Use a transinfarction approach to the VSR, with the site of ventriculotomy determined by the location of the transmural infarction
  • · Inspect the papillary muscles, and concomitantly replace the mitral valve only if frank papillary muscle rupture is present
  • · Trim the left ventricular margins back to viable muscle
  • · Conservatively trim the right ventricular muscle
  • · Close the VSR without tension, using prosthetic material
  • · Buttress the suture line with Teflon pledgets



Percutaneous techniques have been used successfully to close some congenital VSDs. Technical improvements in experimental devices for closing intracardiac shunts are being made to treat postinfarction VSR or residual shunts after primary repair. A balloon catheter introduced percutaneously has been used to abolish the shunt in poor-risk patients.


Patients who require IABPC preoperatively appear to benefit from postoperative support with the pump for 24-72 hours. Some of these patients demonstrate a small persistent or recurrent left-to-right shunt. Because of the large amount of prosthetic material used to repair the septal perforation, anticoagulation therapy in these patients is recommended by some surgeons for a period of 6-8 weeks.


Residual VSDs have been noted early or late after operative treatment in 10-25% of patients. These residual defects are easily diagnosed with the aid of color-flow Doppler investigations. Residual VSDs may be attributable to the reopening of a closed defect, the presence of an overlooked VSD, or the development of a new septal perforation during the early postoperative period.


Reoperation is required for closure of such residual VSDs when the Qp-to-Qs ratio is greater than 2. When the VSDs are small and asymptomatic, a conservative approach may be recommended because spontaneous closure can occur.

Interventional Therapy



Data collected by the Society of Thoracic Surgeons National Database indicate that postinfarction VSD is a lethal disorder, even with treatment. [14] There is considerable interest in the development of percutaneous interventional techniques for closing the ruptured VSD and lowering the mortality.


Isolated reports with the Amplatzer Septal Occluder (St Jude Medical, St Paul, MN) found the technique to be safe for closure of small lesions. [15]


Schlotter et al carried out a comprehensive systematic literature search (13 studies; N=273) to evaluate the existing evidence regarding percutaneous closure of postinfarction VSD. [16] Overall, the technical success rate was greater than 75%, and the device implantation success rate was 89%; however, the overall in-hospital/30-day mortality remained substantial, at 32%. Device embolization, ventricular perforation, and arrhythmias were the major complications of the procedure

Transmyocardial Laser Revascularization

Background


Despite advances in both medical and surgical management of coronary artery disease (CAD), many patients remain symptomatic after conventional therapies have been exhausted. Typically, these patients continue to have chest pain while on maximal medical therapy, and most are at an extraordinary risk for surgical intervention.


Transmyocardial laser revascularization (TMLR) is based on the use of a high-powered carbon dioxide or other laser that interjects a strong energy pulse into the left ventricle, vaporizing the ventricular muscle and creating a transmural channel with a 1-mm diameter. The precise physiologic mechanism for its efficacy is not thoroughly understood.


Although coronary artery bypass grafting (CABG) is effective in many patients, some are not candidates for direct revascularization procedures. TMLR has elicited growing interest for the treatment of otherwise surgically untreatable CAD. Several large clinical studies have shown marked improvements in angina. These improvements appear instantaneously after TMLR and are sustained. In most cases, a comparable improvement in exercise tolerance occurs. Regional myocardial perfusion also may be improved, but this has not been convincingly confirmed on thallium scintigraphy.


The marked improvement in patients with chronic angina led the US Food and Drug Administration (FDA) to approve TMLR for such use. In addition to the carbon dioxide laser energy source, alternative devices using the yttrium-aluminum-garnet (YAG) and excimer lasers have been studied. [1] The latter two sources employ fiberoptic technology and are being evaluated for percutaneous approaches.


The first attempts at improving myocardial blood supply were designed to increase collateral circulation from extracardiac sources. In 1935, Beck used a burr to drill holes into the epicardium and pericardium, intending to stimulate ingrowth of new vessels into the ischemic myocardium.


In 1941, Schlesinger et al observed that intramyocardial arterioles were not prone to arteriosclerosis. This prompted Vineberg to implant the left internal mammary artery (LIMA) directly onto the myocardium with the purpose of developing collaterals between the LIMA and the intramyocardial arterioles. Although the first patient to undergo the Vineberg procedure died 2 days later, the LIMA was found to be widely patent at autopsy. Vineberg later created an intramyocardial tunnel prior to LIMA implantation, and patency of these grafts was documented two decades later.


In 1965, Sen et al studied the benefits of transmyocardial channels produced with needle punctures. [2] Using a canine model, they placed numerous needle punctures in an ischemic area subtended by an occluded left anterior descending artery. They showed that the acupuncture-created channels resulted in decreased mortality, increased long-term survival, and decreased infarct size. Although patent channels were identified at 8 weeks, no evidence suggested that the channels had developed an endothelial cell lining, thus confirming successful rearterialization.


In 1968, Sen et al described marked improvements in patients with chronic angina following transmyocardial revascularization. [3] These initial data supported attempts to improve myocardial perfusion by creating mechanisms for a direct flow of blood from the ventricular cavity to the myocardium, thus mimicking the anatomy of the reptilian heart, in which much of the myocardium is perfused with blood directly from the ventricular cavity.


During the next two decades, numerous studies were undertaken to evaluate the effects of needle-created transmyocardial channels in revascularizing ischemic myocardium. However, much of this research received little attention because it was not considered nearly as promising as the emerging techniques involving direct myocardial revascularization, such as CABG and angioplasty.


The development of laser energy sources in the 1980s stimulated investigators to restudy myocardial acupuncture. In 1981, Mirhoseini et al demonstrated that the carbon dioxide laser could generate small transmyocardial channels in the ischemic myocardium of a dog. [4] In 1983, Mirhoseini et al used TMLR on a patient with CAD, [5] employing a carbon dioxide laser in conjunction with CABG to treat a hypokinetic area of the left ventricle. The patient did well, with normal ventricular function demonstrated during a postoperative nuclear scan.


These initial clinical studies provided further impetus for the use of TMLR. Since the early 1990s, carbon dioxide laser systems have been used to perform TMLR in humans, with excellent results. A holmium:YAG system has also been approved by the FDA. [6]


To date, more than 50,000 TMLR procedures have been done worldwide, nearly one third of them done in the USA alone. Over the past two decades, multiple studies have reported good-to-moderate outcomes. [7]


For patient education resources, see the Heart Health Center, as well as Angina Pectoris and Coronary Heart Disease.

Indications



Although no absolute indications have been described for the application of TMLR, several studies have provided some necessary guidelines.


Most patients have diffuse disease, either locally or globally, such that no target vessel is available for either percutaneous transluminal coronary angioplasty (PTCA) or bypass grafting. Furthermore, the appropriate patient is symptomatic from disease in an area of the myocardium that is not treatable by conventional techniques and has not responded to maximal medical therapy.


Before TMLR is undertaken, a nuclear perfusion scan is obtained, the results of which must show evidence of reversible ischemia. Patients with infarcted or scarred tissue are not suitable candidates for TMLR. Patients should have reasonable ventricular function, with left ventricular ejection fraction (LVEF) above 20%.


Historically, patients enrolled in TMLR clinical trials had severe CAD with Canadian Heart Association class III or IV angina despite maximal medical therapy. The patients had an LVEF above 20% and were on maximal antianginal therapy.

Contraindications



The reported mortality (7-10%) following TMLR is a significant cause for caution. Risk-factor assessment has shown that patients with unstable angina and poor myocardial function are at relatively greater risk. If patients have an LVEF greater than 30% and chronic stable angina, their risk may be minimized.


In addition, patients must have a viable region of the myocardium for TMLR. Patients with scarred or infarcted tissue are not appropriate candidates. Patients with severe adhesions from prior coronary artery bypass surgery can have significant bleeding if a median sternotomy approach is used; therefore, in these patients, a left anterior thoracotomy may be an alternative.



Technical Considerations



Initially, researchers believed that two components were necessary to the success of TMLR for revascularizing myocardium. The first component was thought to be a physical effect: TMLR channels were thought to remain patent secondary to the high intraluminal pressure within the left ventricle. These patent channels would become small sinuses from which diffusion could occur deep within the once-ischemic myocardium and from which cardiac capillaries could communicate and draw oxygen.


This subject has been an area of debate, and histologic data are controversial. Some researchers have observed patency in these channels for a 2-week period, followed by complete occlusion in humans. In animal models, postoperative patency has been achieved for more than 12 months. Gassler et al, describing the histologic features of TMLR at autopsy at various time intervals, [8] showed that no patent channels were created and that endothelialization did not occur. Thus, they concluded that the histologic steps following TMLR are much like those of wound healing following necrosis, resulting in a fibrous scar. They did not describe the clinical response to TLMR in these patients prior to death.


Stimulated by the ongoing debate over the long-term patency of laser channels, several centers reported results of histologic analyses of tissues from patients who died after TMLR. To date, no researchers have reported patent channels from clinical material. Early development of a capillary network has been observed, but the results have not been consistent. Some believe that angiogenesis resulting from the inflammatory response, as opposed to the patent channel hypothesis, may be the reason for improved perfusion.


The second component of successful TMLR is based on the hypothesis that the laser channels activate wound repair mechanisms, thus resulting in increased angiogenesis. This hypothesis is supported by Gassler et al, [8] who noted extensive capillary networks around the laser-created channels in histology sections from a patient 150 days after surgery. The formation of a fibrous scar and the development of capillary networks suggest that the laser actually necroses myocytes, thereby initiating an inflammatory response that, in turn, results in angiogenesis and improved myocardial microperfusion.


A proposed explanation for the success of TMLR is that the process of using a laser to create channels in the ischemic area of the left ventricle actually causes denervation of the myocardium.


Sundt and Kwong noticed a significant decrease in patient symptoms after TMLR. [9] Using the holmium:yttrium-aluminum-garnet (YAG) laser, they performed laser revascularization in canine hearts. Microscopic analysis revealed that laser treatment of the heart tissue might damage or even destroy nerve fibers and thus reduce the symptoms of angina. However, if this were the sole reason for the initial success of TMLR, the long-term outcomes would not be positive, because the original problem of ischemic myocardium would continue to worsen.


Denervation may play a role in the success of TMLR, depending on the type of laser utilized, but the positive effects of denervation are in addition to the increased blood flow that occurs over time in relation to the other mechanisms of action that make TMLR a successful therapy.


Transesophageal echocardiography (TEE) is used to confirm the accurate formation of transmural channels, which occur as a result of vaporization of the red blood cells within the myocardial wall. It is important to have resuscitative equipment in the operating room because touching of the myocardium and generation of the laser beam can sometimes trigger ventricular arrhythmias.

Outcomes



Most clinical studies show that TMLR, regardless of the type of laser used, results in profound and almost immediate improvement in angina pectoris among patients with inoperable CAD. This improvement appears to be sustained throughout the first year. TMLR also offers advantages over CABG in that it does not require arresting the heart or insituting cardiopulmonary bypass (CPB).


A review of TMLR by the FDA recommended that TMLR not be considered experimental, because the latest data support its efficacy and safety. Clinical trials are in progress that randomize patients to continued medical therapy or to TMLR. A 2015 Cochrane review of TMLR versus medical therapy for refractory angina concluded that overall, the risks associated with TMLR outweighed the potential clinical benefits. [10]


Trials are also under way that compare TMLR with reoperative CABG. Other studies are examining the use of TMLR in combination with CABG. If the combination of TMLR and CABG proves beneficial, TMLR could be used in areas where bypass grafting is not possible. TMLR may prove helpful in the treatment of cardiac transplantation patients with diffuse atherosclerosis. Also, TMLR will most likely be performed via minimally invasive approaches in the future.


The use of TMLR via the endocardial approach is an important subject of clinical study. TMLR performed via the endocardial approach creates transmural channels through the myocardium, initiated at the endocardial surface and extended toward the pericardium, by using the holmium:YAG laser. The obvious benefits of this technique are that it can be performed via a percutaneous approach in the cardiac catheterization laboratory and that it obviates the need for surgery.


A robotically assisted completely endoscopic approach to TMLR was found to be feasible and effective in a study of 42 patients with Canadian Cardiovascular Score class IV angina at baseline. [11]


Clinical investigations are evaluating alternative energy sources potentially adaptable to endovascular applications. The final use of this type of treatment, whether delivered percutaneously or surgically, will be determined only when the results of prospectively randomized trials of maximum medical therapy versus TMLR are available and the impact of this therapy on survival and symptom relief are known.

Short-term clinical experience



Numerous studies have reported on the use of TMLR. In most patients, preoperative and postoperative evaluations include positron emission tomography (PET), dobutamine echocardiography, thallium stress testing, radionuclide ventriculography, and an exercise treadmill test to evaluate the results of TMLR. Thallium dipyridamole scans and dobutamine stress echocardiograms have shown an overall definite, statistically significant reduction in the severity and extent of ischemic myocardium and improvements in resting function and contractile reserve.


The initial report by Mirhoseini et al on 12 patients whose conditions were refractory to medical treatment and who were not candidates for either CAGB or angioplasty revealed no deaths, and all patients improved both clinically and according to nuclear scan findings. [12] This initial report and subsequent follow-up eventually led to phase 2 trials.


Frazier et al reported the use of TMLR in 21 patients with medically refractory, chronic stable angina who were not candidates for traditional revascularization procedures. [13] This study showed a concomitant reduction in antianginal medications and cardiac-related hospital admissions.


Without question, the most dramatic clinical effect of TMLR has been a significant reduction in angina pectoris. In patients with Canadian Heart Association stage III or IV angina, perioperative mortality was 9%. Postoperatively, most patients improved to class II or better. Remarkably, much of this benefit was observed immediately after the operation.


In multicenter studies, one third of patients reported complete relief of angina, whereas two thirds experienced at least a two-class reduction in symptoms. In addition, the admission rate for angina pectoris in multicenter series dropped significantly in patients treated with TMLR. Note that myocardial perfusion, as determined by single-photon emission computed tomography (SPECT), was significantly improved in ischemic areas that had received TMLR.


Long-term studies have unequivocally demonstrated the superiority of TMLR in decreasing angina. Five-year follow-up of patients who had refractory class IV angina and were not candidates for conventional therapy demonstrated significantly increased Kaplan-Meier survival estimates in patients randomized to TMLR. The significant angina relief observed 12 months after sole TMLR therapy was sustained over the long term and continued to be superior to that observed for patients maintained on continual medical management alone.


Improvements in myocardial perfusion after TMLR have been less convincing than its impact on clinical symptoms. Study findings have not been uniform, with most showing no difference between baseline and 12-month studies of ejection fraction using nuclear studies. In addition, studies have not defined major differences in short-term morbidity and mortality between the holmium:YAG laser and the CO2 laser in the setting of TMLR. [14]


TMLR has also been used in cardiac transplantation patients who have accelerated graft atherosclerosis documented by angiography findings. Angiograms revealing patency of channels after TMLR in symptomatic patients have been described. [15]


Reports indicate that TMLR provides excellent relief of angina in these patients. Clinical trials have been initiated in many centers in the United States and Europe.


TMLR has been combined with intramyocardial autologous endothelial progenitor cell injections for angina relief. To date, studies have only included a small number of patients, and the follow-up has been short. The one conclusion derived from the study is the great caution should be exercised when this therapy is employed in patients with depressed left ventricular function. [16]
CABG combined with TMLR


Over the past few years, increasing evidence has shown that TMLR may be more useful as a hybrid procedure when used in combination with CABG. Several randomized studies have shown that the combination of TMLR and CABG yields more clinical benefit than TMLR or CABG alone. In a prospective, randomized trial involving 263 patients who were not completely revascularized with CABG alone, the addition of TMLR to conventional CABG provided superior anginal relief as compared with CABG alone.


Other studies have shown similar results. When TMLR was used (both alone and in combination with CABG), substantial improvement was noted with regard to the anginal score, exercise tolerance, and left ventricular function 6 months after the procedure. In summary, most studies have shown that TMLR, as an adjunct to CABG in selected patients with limited options, may improve hospital outcomes.

Percutaneous TMLR



Traditonally, TMLR has always been done by opening the chest. To reduce the morbidity of surgery and anesthesia, a minimally invasive percutaneous approach to TMR has been attempted. Both radial artery and femoral artery approaches to the left ventricle have been undertaken. The laser fiber is then guided by electrical mapping and used to create 2- to 3-mm small pockets in the subendocardial tissue.


To date the results from small series of percutaneous TMLR have not been impressive. There appears to be a high rate of periprocedural adverse events such as bleeding and even tamponade. The key reasons why percutaneous TMLR has not been successful are that the technique only permits creation of a few holes and that locating the exact lesion within the beating myocardium is difficult. [17]

TMLR with stem cell therapy



Over the past decade, many studies have looked at the use of stem cells to regenerate infarcted myocardium. Several animal and human studies have evaluated TMLR in conjunction with delivery of stem cells. Isolated reports indicate that this therapy is safe and can even improve the angina class. However, these studies should be considered experimental, in that they have many limitations with respect to delivery, type of differentiation, and outcome evaluation. A small clinical trial is assessing the effects of TMLR with injection of autologous mesenchymal stem cells.

Preprocedural Planning



Although clinical trials studying the effects of transmyocardial laser revascularization (TMLR) differ in protocol, eligible patients are provided information regarding the potential benefits and risks of this procedure. The workup before the procedure includes a complete history, physical examination, chest radiography, and echocardiography. Regions of the left ventricle to be treated by TMLR are identified on the basis of ischemic areas noted on the preoperative thallium scan image.


The surgical team does not have to wear special protective gowns during TMLR, but eyes must be shielded with special glasses.


Equipment



A number of different laser technologies were developed while TMLR with the carbon dioxide laser was undergoing US Food and Drug Administration (FDA)-approved trials. The FDA has approved one carbon dioxide system and one holmium:yttrium-aluminum-garnet (YAG) system for this application. [6] The experience described in this article focuses on the carbon dioxide laser. Other laser technologies are not coordinated with electrocardiography (ECG) and therefore may not protect against ventricular arrhythmias. Additionally, the other laser technologies do not produce high energy; therefore, they do not protect against perichannel burns and other forms of tissue destruction around the channels.

Patient Preparation



Patients must be prepared and draped in the same manner that they would be for any open heart procedure. Most patients have a Swan-Ganz catheter and an arterial line placed for monitoring. In any reoperative case, external defibrillator pads are applied before the incision is made.


TMLR is performed with the patient under general anesthesia without the use of cardiopulmonary bypass (CPB) or anticoagulation. A double-lumen endotracheal tube is used to allow selective ventilation of the right lung, thus affording better exposure of the heart during the procedure. For monitoring, all patients need ECG, arterial pressure monitoring, Swan-Ganz catheterization, and transesophageal echocardiography (TEE).


TEE is used to confirm the accurate formation of transmural channels, which occur as a result of vaporization of the red blood cells within the myocardial wall. It is important to have resuscitative equipment in the operating room because touching of the myocardium and generation of the laser beam can sometimes trigger ventricular arrhythmias.


Monitoring & Follow-up



TMLR is no longer an experimental procedure. Numerous trials have been completed, and long-term follow-up data are being collected. Regular follow-up care includes a history, a physical examination, and an evaluation of angina and quality of life. A series of tests, including echocardiography, thallium scanning, and exercise tolerance testing, are regularly performed. Whether TMLR has a significant impact on overall mortality in this patient population remains to be determined.




Transmyocardial Laser Revascularization Technique



Approach Considerations



Transmyocardial laser revascularization (TMLR) is based on the use of a high-powered carbon dioxide or other laser that interjects a strong energy pulse into the left ventricle, vaporizing the ventricular muscle and creating a transmural channel with a 1-mm diameter. The procedure can be used to create channels along the free left ventricular wall but not the septum. These channels are placed 1 cm apart in the ischemic myocardium. TMLR is performed to improve myocardial oxygenation, eliminate or reduce angina, and improve the patient's cardiovascular function.


The carbon dioxide laser is triggered to the electrocardiogram (ECG) to prevent arrhythmias (ventricular tachycardia). Cardiopulmonary bypass (CPB) is not required, and the patient is not heparinized. TMLR is a less invasive procedure, and it is appropriate for minimally invasive surgical incisions. Blood transfusions are rarely required, and recovery appears to be faster and less traumatic.


Clinical trials are investigating the benefits of TMLR compared with continued medical management for patients with angina who are not candidates for either percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG). To date, studies of TMLR have shown marked decreases in angina and improved functional status for patients with chronic angina.


The precise physiologic mechanism for the efficacy of TMLR is not thoroughly understood. Initially, blood was presumed to flow to the intraventricular chambers through the newly created channels. Today, it is unclear whether this is the exact mechanism by which myocardial blood flow is improved. One theory, albeit an unproven one, is that angiogenesis (growth of new blood vessels) may occur in response to the myocardial tissue injury caused by the laser energy; this may be the process that eventually leads to improved myocardial oxygenation.



Use of Laser to Create Transmural Channels in Left Ventricle



The heart is approached via an anterolateral thoracotomy through the fifth and sixth intercostal spaces, and the pericardium is opened. Because most of these patients have had prior surgery, all dense adhesions must be carefully excised. In Europe, the thoracoscopic approach has been used in some patients who have not had previous operations.


The energy level for the laser is usually set at 15-60 J, corresponding to a pulse duration of 20-50 ms. The laser probe is placed in contact with the epicardium and fired, thereby vaporizing the myocardium in its path and creating a 1-mm wide channel that extends from the surface of the heart to the ventricular cavity. (See the images below)



TMLR can be performed with a carbon dioxide laser or a holmium:yttrium-aluminum-garnet (YAG) laser. Carbon dioxide lasers can deliver up to 1000 W of energy through the myocardium. ECG electrodes are used to synchronize the pulsed carbon dioxide laser to fire with the R wave (corresponding to end diastole), thus minimizing the risk of ventricular arrhythmias. Transesophageal echocardiography (TEE) is used to confirm channel creation when transmural penetration is successful. On the TEE image, steam or bubbles are visualized.


The holmium:YAG laser transmits energy through optical fibers. Because the energy is more readily dissipated, three or four firings are usually required to pass through the entire myocardium. Regardless of the type of laser used, the laser energy vaporizes the myocardial tissue. One channel is created for approximately every 1 cm2 of ischemic myocardium; thus, a total of 20-40 channels are usually required.


Bleeding from the epicardial surface stops quickly, though local pressure or a suture may occasionally be required to achieve hemostasis. Once the desired number of channels has been created and hemostasis obtained, chest tubes are placed in the pericardial cavity and the incision is closed. An intraoperative TEE study is performed to exclude any injury to the mitral valve apparatus or the septum.


After 20-40 channels are drilled, the pericardium is loosely reapproximated. The chest is then closed in the usual fashion for a small thoracotomy.

Complications


In more than 1500 patients, intraoperative analysis has documented little morbidity. During the postoperative period, occasional supraventricular tachycardia, pleural effusions, and incisional pain from the thoracotomy have been observed. Because perfusion pressure determines perfusion of the collateral coronary circulation, maintaining adequate perfusion pressure until the patient has recovered completely is important. Hypotension must be avoided, and myocardial support with the use of intra-aortic balloon pumping is sometimes required.


Postoperative myocardial infarctions have been reported and are associated with a mortality of 8-10%. Mortality also appears to be correlated with the left ventricular ejection fraction in all the national studies, with highest early and late mortality in patients with worse left ventricular function.

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