Carcinoid Heart Disease

Basics

Description

Carcinoid heart disease (CHD) is seen in ~50% of patients with metastatic carcinoid tumors and carcinoid syndrome. CHD is caused by diffuse deposits of fibrous material most prominently on the endocardium of the right heart. The result is primarily tricuspid regurgitation with mild stenosis, and mixed stenosis and regurgitation of the pulmonic valve.

Epidemiology

Incidence
Yearly incidence of carcinoid tumors in the U.S. is 1-2 per 100,000.
Prevalence

~10% of patients with carcinoid tumors develop carcinoid syndrome.
~50% of patients with carcinoid syndrome develop CHD.

Risk Factors

Patients with the highest serotonin levels are more likely to have cardiac involvement.

Pathophysiology

Grossly, plaques may be focal or diffuse, white, shiny, and fibrous.
The plaques are comprised of myofibroblasts, smooth muscle cells, extracellular matrix and an endothelial layer and are deposited on the endocardium of the valvular leaflets, subvalvular apparatus, cardiac chambers, vena cava, pulmonary artery, and coronary sinus.
Plaques preferentially involve the ventricular surface of tricuspid valve leaflets and the arterial aspect of the pulmonic valve.
The characteristic fibrous thickening is associated with retraction of the tricuspid apparatus and valve, and thickening and retraction of the pulmonic valve.
Carcinoid and pancreatic endocrine tumors are part of a group of neuroendocrine tumors, which have in common the ability to secrete peptide hormones and biogenic amines.
Carcinoid tumors arise from the enterochromaffin cells typically of the GI tract (midgut carcinoids) or the lungs (foregut carcinoids).
70% of carcinoid tumors arise in the GI tract most commonly in the jejunoileum, then rectum and appendix.
The vasoactive substances, including serotonin (5-hydroxytryptamine), bradykinin, histamine, 5-hydroxytryptophan, and prostaglandins released by carcinoid tumors cause the signs and symptoms of carcinoid syndrome.
Ordinarily, the vasoactive substances are inactivated by the liver or lung, but with liver metastases, the right heart is exposed to high levels of vasoactive substances which in turn result in endocardial fibrotic plaques in the right heart. The precise cause for plaque formation is not clear but may be due to the direct actions of serotonin and bradykinin.
In the vast majority of patients only the tricuspid and pulmonic valves are affected, since the lung inactivates the vasoactive substances, thus protecting the left heart.
Left-sided valve involvement occurs in the presence of a right-to-left intracardiac shunt such as a patent foramen ovale, intrapulmonary shunting, or with bronchial carcinoid or pulmonary metastases (5-10% cases).
Thickening, shortening and retraction of the tricuspid and pulmonic valves result in predominant tricuspid insufficiency, usually with mild stenosis and mixed pulmonic stenosis and insufficiency.
The result of the valve abnormalities and the RV endocardial fibrosis results in right heart failure, due to a combination of tricuspid regurgitation, mild to moderate pulmonic stenosis and restrictive RV filling.

Associated Conditions

Carcinoid tumors may be associated with elevated levels of gastrin, glucagons, insulin, adrenocorticotropic hormone (ACTH).

Diagnosis

History

1/2 of patients with carcinoid syndrome will have CHD.
The syndrome consists of cutaneous vasomotor flushing (90% of patients), telangiectasias, GI hypermotility, secretory diarrhea, bronchospasm, and hypotension.
Patients with CHD may have symptoms of right heart failure with edema, abdominal discomfort, anorexia, and fatigue due to hepatic congestion.
Serotonin can lead to tachycardia and hypertensive crisis refractory to traditional therapy.
Patients may have labile BP, with high or low BP depending on the relative amounts of vasoactive substances in the blood.
Carcinoid symptoms typically occur at a mean age of 55-60 yr.
The time period between the onset of carcinoid syndrome and the diagnosis of CHD averages 24-28 mo.
Patients may have complaints of flushing, diarrhea, and wheezing suggestive of carcinoid syndrome.
There may be symptoms of right heart failure: Lower extremity swelling, abdominal pain and bloating, constipation, anorexia, and early satiety.

Physical Exam

Many of the patients with CHD will present with signs of right heart failure: Edema, hepatomegaly, ascites, hepatojugular reflux, and elevated jugular venous pressure.
In the presence of ascites and/or anasarca, careful attention must be paid to the jugular veins to distinguish right heart failure from cirrhosis with ascites.
Prominent systolic venous pulsations may be seen in the jugular veins with significant tricuspid regurgitation.
A systolic murmur of TR is present in 2/3 of patients. Unlike the murmur of MR, it varies with respiration.
Pulmonic stenosis or regurgitant murmurs may also be present.

Tests

Lab

Carcinoid tumors convert tryptophan to serotonin which is metabolized to 5-hydroxyindole acetic acid (5-HIAA).
Elevated levels of urinary 5-HIAA have a 75% sensitivity and a 100% specificity for carcinoid.
Levodopa, ethanol, imipramine, aspirin, and phenothiazines may falsely lower urinary 5-HIAA levels.
Acetaminophen, guaifenesin, ephedrine, nicotine, caffeine, and phenobarbital may falsely increase urinary 5-HIAA levels.
Diets rich in banana, kiwi, eggplant, nuts, pineapple, and avocado may falsely increase urinary 5-HIAA levels.
Right heart failure may cause elevated liver function tests due to passive hepatic congestion.
ECG: Most X commonly non-specific ST-T changes. Few patients will have evidence of conduction abnormalities, right atrial abnormality.

Imaging

CXR:
- Cardiomegaly is seen in ~50% of patients.
- Pleural effusions and metastatic pleural plaques are late findings.
Echo:
- The tricuspid valve leaflets are thickened, shortened, retracted into the RV cavity and fail to coapt.
- In most patients, the leaflets appear rigid, immobile and fixed in a semi-open position.
- The pulmonic valve is likewise thickened and appears immobile.
- Doppler echo demonstrates moderate to severe tricuspid insufficiency in the majority of patients with CHD, and usually mild stenosis. Mild to moderate pulmonic insufficiency and mild to moderate pulmonic stenosis can also be demonstrated.
- Right atrial and RV enlargement are present in >90% of cases of CHD.
- Abnormal ventricular septal motion is present in 50% of CHD due to RV volume and/or pressure overload.
- Calcification and doming of the valves is not associated with CHD.
Other Imaging:
- CT or MRI
- Tumor localization by pentreotide (Indium 111 octreotide) scanning

Differential Diagnosis

Other causes of isolated right-sided heart failure (eg, restrictive cardiomyopathy, primary pulmonary HTN)
Rheumatic heart disease (RHD), when RHD involves the tricuspid valve, the mitral is inevitably involved, while the mitral valve is only rarely involved in CHD (see above)
Pheochromocytoma

Treatment

Medication

Right heart failure is managed with diuretics and possibly ACE inhibitors.
Somatostatin analogs octreotide and lanreotide (long-acting octreotide) have become standard therapy to provide symptomatic relief by reducing the vasoactive peptides. While improving symptoms in 1/2 of these patients, there is, as yet, no demonstrated effect on the cardiac lesions.
Chemotherapy for carcinoid tumors has not shown any significant benefit and is rarely used.

Additional Treatment

General Measures

Patients with CHD have metastatic carcinoid disease and treatment of the tumor itself is palliative.
CHD therapies focus on the symptomatic treatment of right heart failure with salt and fluid restrictions and sometimes lower extremity compression stockings.
Hepatic artery embolization may reduce the hepatic metastatic tumor burden and reduce the carcinoid syndrome symptoms.
The abnormalities of CHD are not reversible despite reductions in the levels of vasoactive substances by somatostatin antagonists and control of vasomotor symptoms.

Issues for Referral

Patients with carcinoid tumors should be monitored regularly for evidence of metastatic disease and CHD.
Once CHD is diagnosed, referral to cardiology and cardiothoracic surgery is prudent.

Surgery

While surgical resection of a localized carcinoid tumor can be curative, patients with CHD have metastatic disease and thus cannot be cured.
Surgical options are palliative and not curative, but may increase median survival.
Surgery, only indicated in patients whose systemic symptoms are controlled, is the only truly effective therapy for the valve abnormalities of CHD.
Balloon angioplasty can produce improvement in right heart failure, but symptoms may recur. When significant valve insufficiency is already present, as it usually is, balloon valvuloplasty is contraindicated.
Indications for valve replacement surgery are poor exercise tolerance, worsening fatigue, or a reduction in ventricular function, despite an otherwise indolent course of metastatic carcinoid syndrome.
Mechanical valves in the TV position are not affected by the vasoactive peptides but are complicated by the need for chronic anticoagulation with coexisting liver metastases.
Bioprosthetic valve durability will likely outlast the patient's lifespan and are generally preferable, but the valves can be affected by CHD.
TV repair is not usually an option due to underlying leaflet damage.
The pulmonary valve may be managed with a valvectomy or a valve replacement.
Pulmonary valve replacement may reduce postoperative right heart dilatation.

In-Patient Considerations

Admission Criteria
Patients with right-sided heart failure exacerbations may require hospital admission.
Discharge Criteria
Patients can be discharged once they have adequate resolution of their admission symptoms and stabilization of their heart failure.

Ongoing Care

Prognosis

In 1 large observational series looking at survival over 3 time periods over 2 decades, overall median survival from 1st diagnosis of CHD was 2.6 yr, and from 1st diagnosis of metastatic carcinoid disease, 5.9 yr. In the most recent cohort, those patients who underwent valve surgery had an apparent improved median survival.
Patients with CHD usually die of severe TR and right heart failure rather than carcinomatosis.

Additional Reading

1
Bernheim AM, Connolly HM, Pellikka PA.
Carcinoid heart disease. Curr Treat Options Cardiovasc Med. 2007;9:482-489. [View Abstract] 2
Bonow RO, Carabello B, de Leon ACJr. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients with Valvular Heart Disease). American College of Cardiology Web Site. Available at: content.onlinejacc.org/cgi/reprint/48/3/el. 3
Connolly M. Outcome of cardiac surgery for carcinoid heart disease. J Am Coll Cardiol. 1995;25:410-416. [View Abstract] 4
Fox DJ, Khattar RS.
Carcinoid heart disease: Presentation, diagnosis and management. Heart. 2004;90:1224-1228. [View Abstract] 5
Knott-Craig CJ, Schaff HV, Mullany CJ. Carcinoid disease of the heart: Surgical management of ten patients. J Thorac Cardiovasc Surg. 1992;104:475-481. [View Abstract] 6
MâŠ˜ller JE, Pellikka PA, Bernheim AM. Prognosis of carcinoid heart disease: Analysis of 200 cases over two decades. Circulation. 2005;112:3320-3327. [View Abstract] 7
Pellikka PA, Tajik AJ, Khanderia BK. Carcinoid heart disease. Clinical and echocardiographic spectrum in 74 patients. Circulation. 1993:87:1188-1196. [View Abstract] 8
Toumpanakis C, Garland J, Marelli L. Long term results of patients with malignant carcinoid syndrome receiving octreotide LAR. Alim Pharm Ther. 2009;30:733-740. [View Abstract]

Home

Erectile Dysfunction

Doctor123.org