Cardiac Calcifications

Etiology

Coronary Artery Calcifications

There are two distinct forms of vascular calcifications, medial calcification, and intimal calcification. Medial calcifications (involving tunica media) are seen in patients with disturbance of calcium and phosphate homeostasis. These are patients with hypercalcemia, hyperparathyroidism, hyperphosphatemia, and end-stage renal disease which is the most common cause of medial calcification and duration of dialysis correlates with the degree of calcification. Intimal calcifications (involving tunica intima) represent atherosclerotic coronary artery disease (CAD), and it is related to advanced age. Other traditional risk factors include hypertension, smoking, diabetes, hyperlipidemia, metabolic syndrome, and chronic kidney disease.[3]

Valvular Calcifications

Age-related degeneration is the most common cause of calcification of the valves. However, patients with disturbance in calcium and phosphate hemodynamics (hypercalcemia, hyperphosphatemia, and hyperparathyroidism, as well as end-stage renal disease) are more prone to develop valvular calcifications.[4]

Pericardial and Myocardial Calcifications

Any previous infection (tuberculosis) or previous radiation exposure leads to constrictive pericarditis is marked by calcium deposits in the pericardium. Myocardial calcifications are related to previous global myocardial injuries (sepsis, myocardial infarction, radiation-induced myocardial injury, previous myocarditis). However, any disturbance in calcium and phosphate metabolism can accelerate the myocardial and pericardial calcifications.[5]

Epidemiology

The presence of cardiac calcifications is age-dependent. Around 90% of men and 67% of women older than the age of 70 years have such calcifications (particularly the coronary artery calcifications). According to one study, the prevalence of coronary calcification in Whites, African Americans, Hispanics, and Chinese males is 70.4%, 52.1%, 56.5%, and 59.2%, respectively, and in females is 44.6%, 36.5%, 34.9%, and 41.9% respectively.[6]

Pathophysiology

Two distinct pathological mechanisms for calcifications anywhere in the body are dystrophic calcifications, calcification of dead and dying tissues and metastatic calcification, calcification of normal living tissue. Metastatic calcification is usually related to disturbances in homeostasis of calcium. While dystrophic calcification is not related to any disturbance in calcium metabolism and can occur with normal calcium and phosphorous levels in the blood.[7]

History and Physical

Patients with coronary artery calcifications are usually asymptomatic or may complain of exertional symptoms of chest pain and dyspnea. Past history should focus on the presence of atherosclerotic cardiovascular disease (ASCVD) risk factors like hyperlipidemia, diabetes, hypertension, and smoking. Patients with valvular calcifications may present with exertion chest pain, dyspnea or syncope/near syncope depending on the severity of valve calcification and stenosis. Physical examination may reveal a murmur depending on the valve involved. Patients with pericardial calcifications may present with symptoms of right-sided heart failure, including ascites and pedal edema. They usually have a previous history of infection or radiation exposure. The examination is significant for a raised jugular venous pulse and positive Kussmaul's sign, fluid shift, and dullness to percussion in the abdomen. In patients with myocardial calcification, a history of preceding global or focal myocardial injury is usually present. A previous history of severe sepsis or septic shock may also be present in such patients.

Evaluation

Coronary artery Calcifications (CAC)

A cardiac CT angiogram (CTA) is better at demonstrating the CAC and also quantifying it. This is particularly important in asymptomatic patients who have an intermediate (10% to 20%) 10-year risk of ASCVD based on the Framingham risk score, as well as for asymptomatic individuals 40 years and older with diabetes mellitus for coronary artery calcium scanning.[8]

Currently, the American College of Cardiology/American Heart Association gives class IIa indication for asymptomatic patients with an intermediate 10-year risk of ASCVD (10% to 20%) based on Framingham risk score, as well as for asymptomatic individuals 40 years and older with diabetes mellitus. CAC measurement is generally not recommended for patients at low (less than 10%) or high (greater than 20%) 10-year risk of cardiac events based on the Framingham risk score.[9]

Quantification of CAC is based on Agatston score calculated using CTA of coronary arteries is as follows;

• 0: no identifiable disease
• 1 to 99: mild disease 
• 100 to 399: moderate disease
• Greater than 400: severe disease

In general, the extent of CAC correlates with coronary artery disease burden and does not exactly tell us about the degree of stenosis for which coronary angiogram or other intravascular imaging modalities are needed.

Valvular Calcifications

Aortic valve stenosis is the most common valve pathology in the elderly. It is usually diagnosed by an echocardiogram, which tells us the valvular area as well as valvular gradients. Severe AS is usually diagnosed by valve area of < 1 cm2, peak velocity of > 4 m/sec and mean gradient of > 40 mmHg. Accurate diagnosis of severe AS relies on a normal contractile function of the heart. In cases of left ventricular failure, severity may be misdiagnosed on echocardiogram. Aortic valve calcium scoring (not very readily available) is a quantitative and flow –independent method of assessing the AS severity (recommended thresholds of 2000 in men and 1250 in women). Similarly, for other calcified valves, an echocardiogram can predict the severity of stenosis as well.[10]

Pericardial and Myocardial Calcifications

For pericardial calcifications seen on chest x-ray or CT scan in patients with signs and symptoms of right heart failure, a thorough investigation of the right heart function should be done, including a right heart catheterization as well as an echocardiogram. Pericardial calcification is usually diagnosed as a rim of calcification or spotty calcification involving the pericardium.[11]

Myocardial calcifications are usually diagnosed as incidental findings on chest imaging or autopsy of patients. A predisposing global cardiac injury like ischemia or sepsis is usually present in these patients.

Treatment / Management

Coronary Artery Calcifications

There is no known treatment for coronary artery calcifications. As mentioned above, a certain threshold of CAC risk score predicts which patients would benefit from statins and hence should be prescribed per the guidelines. In addition, other modifiable risk factors for ASCVD, including hypertension, diabetes, and cigarette smoking, should be addressed.[12][13]

Valvular Calcifications

For valvular calcifications and stenosis that fulfills the criteria for valvular replacement, either a transcatheter or surgical valve replacement procedure should be performed. This should take into account the frailty of the patient as well as the surgical risks, calculated using the STS score (Society of Thoracic Surgeons). While surgery is preferred in young patients, a transcatheter aortic valve replacement (TAVR) may be more desirable in patients with higher surgical risks.[14]

Pericardial and Myocrdial Calcifications

In addition to medical management of heart failure with diuretics and other guidelines directed medical treatment (GDMT), a pericardiectomy may be necessitated in refractory constrictive pericarditis. Pericardiectomy is a procedure with high morbidity and mortality rates. 

The treatment of myocardial calcifications is not well elucidated in the literature.

Differential Diagnosis

The most important differential diagnosis of coronary artery calcifications is coronary artery disease. On chest imaging, including CT scans, it may be difficult to distinguish calcifications of the coronary artery, valves, annulus, pericardium, great vessel, cardiac lumen, and myocardium. However, advanced imaging, like echocardiography and cardiac MRI, as well as cardiac CTA, can help predict the precise locations of these calcifications.

The morphology of calcifications on chest imaging can provide clues to its source in difficult cases. Coronary artery calcifications follow an expected anatomic course and usually are linear. Pericardial calcifications are usually dense but oriented in a linear configuration and usually spare the apex. Calcifications of the mitral annulus are arranged in dense ring-like clumps, whereas valvular and great vessel calcifications are thin and curvilinear and located in an expected anatomic location. Myocardial calcifications are diffuse and frequently involve the septum. 

Prognosis

CAC score is of prognostic value. A score of 400 or more indicates an increased risk of ASCVD events, while a lower score predicts a lower risk. This score can be used complementary with other ASCVD risk prediction models. In patients with intermediate-risk of ASCVD using the Framingham score, a CAC of 0 will indicate a lower risk when these two scores are combined. Similarly, in patients with an intermediate ASCVD score, a high CAC will predict the risk of future ASCVD events to be high when combined with the original score.[15]

The severity of valvular stenosis is calculated by echocardiogram based on visual and hemodynamic estimations. Severe aortic valve stenosis carries a poor prognosis, especially with symptoms present.[16]

The prognosis of pericardial calcification can be predicted by signs and symptoms of heart failure. If the symptoms are refractory to medical management, they indicate poor prognosis. In these cases, surgical management is required. 

The prognostic value of myocardial calcification is not clear. For now, it is merely recognized as an incidental finding on various imaging modalities or autopsy.

Complications

Coronary artery calcifications, if not addressed, can lead to worse cardiovascular outcomes. Aggressive lifestyle modification and high dose statin in asymptomatic patients with high coronary artery calcium scores are required to reduce the risk of future events. Pericardial calcifications can lead to worsening constrictive pericarditis and symptoms of refractory heart failure. Myocardial calcifications in the long-run can lead to an impaired diastolic filling.[16]