Periyasamy Pillai Sathananthan, MD

Heart failure is a common disorder with high morbidity and mortality. It is the only major cardiovascular disease whose prevalence and incidence are not only on the increase but predicted to reach epidemic proportions.1 This increase is due to an aging population, increased life expectancy, and improved survival of patients with acute coronary syndromes.

Heart failure is a complex syndrome that can result from heterogeneous disorders (see table). It lacks a universally accepted definition or definitive diagnostic investigation. Unspecific symptoms, the presence of asymptomatic disease, and the possibility of other diseases that mimic symptoms of heart failure all add to the diagnostic dilemma.

Many imaging modalities play important roles in the diagnosis of heart failure, detection of its underlying etiology, and observation of disease progression and response to treatment. None is ideal. Cardiac MRI, however, shows great potential.

The pathophysiological definition of heart failure is "a state in which the heart is unable to pump blood at a rate commensurate with requirements of metabolizing tissues or can do so only from an elevated filling pressure." American Heart Association/American College of Cardiology (AHA/ACC) guidelines define it as a "complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood."2

Neither of these definitions is very useful clinically. The European Society of Cardiology's heart failure task force considers that patients should have symptoms or signs of heart failure and objective evidence of cardiac dysfunction at rest. They note that doubtful diagnoses can be confirmed by assessing a patient's response to treatment for heart failure.3

Twenty-three million people worldwide (6.5 million in Europe, five million in the U.S.) currently suffer from heart failure.1 Between 0.4% and 2% of the general European population are estimated to have clinically identified heart failure, rising to more than 10% in those over 65 years old.2 The prevalence of asymptomatic heart failure is approximately the same.

Despite several advances in early diagnosis and management, the long-term prognosis associated with heart failure remains poor. About 50% of all patients diagnosed with heart failure die within four years, and of these, 50% with end-stage heart failure die within a year. The five-year survival rate is lower than all malignancies with the exception of lung cancer. Heart failure is consequently considered to be more "malignant" than cancer.4

Coronary artery disease is the most common cause of heart failure, accounting for 70% of cases in the developed world.5 Patients with systemic hypertension, diabetes mellitus, a history of cardiotoxic drug therapy or alcohol abuse, and a family history of heart failure are at high risk of developing the condition. In most instances, however, multiple pathologies contribute to the development of heart failure, and primary pathology may not be identified.

Systolic heart failure, due to impaired systolic function, results from high or low output status. It can involve the left or right ventricle, or both. Patients presenting with features of heart failure who have preserved ejection fraction but an abnormal diastolic function are described as having diastolic heart failure. Diastolic heart failure has its own diagnostic and therapeutic implications.

It is prudent to have a simple, safe, cost-effective, and readily available investigation for the accurate and reproducible assessment of cardiac function. The chosen tool should also reveal the underlying etiology and any contributory causes of heart failure. It should be suitable for serial assessments that can guide timing and modes of intervention, optimize drug therapy, and monitor treatment response. None of the traditional imaging modalities can provide such a comprehensive service.

Cardiac MRI is a relatively new addition to the imaging armamentarium that is showing great potential for becoming the imaging investigation of choice for heart failure. Quantification with cardiac MRI is accurate, as it does not make geometric assumptions of ventricular shape like echocardiography, which is the most commonly used imaging modality. It has also been validated for measuring ventricular volumes and mass.6-12 Cardiac MRI has excellent interstudy reproducibility that is superior to echocardiography, while its unrestricted field-of-view provides structural and functional flow information on the heart and coronary arteries in a single test.13,14 It is safe and noninvasive and does not involve the use of ionizing radiation or nephrotoxic contrast agents.

Image quality can be compromised, however, by orthopnea, respiratory motion artifacts, and arrhythmias. Between 1% and 4% of patients will suffer from claustrophobia in the scanner. Cardiac MRI is also unsuitable for individuals with pacemakers and/or implantable defibrillators.15

Quantitative and qualitative assessment of cardiac function is important in the diagnosis and temporal follow-up of heart failure. Cardiac MRI can quantify the global cardiac function and ventricular volume and mass accurately (Figure 1). Regional contractile function can be assessed qualitatively by direct visualization and semiquantitatively by myocardial tagging technique at rest and stress. Diagnosing diastolic dysfunction in the presence of a preserved systolic function poses further challenges. Assessment of mitral and tricuspid flow allows the pressure-volume relationship of ventricles to be assessed in a fashion similar to that of echocardiography.

Ischemic heart disease is the single most common cause of heart failure. Perfusion abnormalities precede cardiac dysfunction, ECG changes, and symptoms. Early detection with appropriate therapeutic intervention can reduce the incidence of heart failure. Detection of a viable myocardium is of great importance to interventionalists and cardiac surgeons. The combination of delayed-enhancement cardiac MRI, with or without low-dose adenosine/ dobutamine, may be used to differentiate hibernating myocardium from scar tissue and normal myocardium.16 Myocardial scars appear as hyperenhanced and noncontracting. Hibernating myocardium is noncontracting as well but without hyperenhancement.

T1-weighted sequences with appropriate inversion times are obtained 10 to 15 minutes following intravenous administration (0.2 mmol/kg gadolinium) for the assessment of delayed enhancement (Figure 2). Spatial resolution is around 2 mm, which helps to delineate the extent of transmural viability.

Cardiac MRI can also assess wall motion quantitatively and qualitatively, at rest and stress, to detect ischemia. Assessment of epicardial coronary arteries is possible but limited by lower sensitivity for the detection of distal coronary arteries.13,14 Coronary flow measurement is still an experimental technique, but it has potential for detecting small-vessel disease. Effects of ischemia, such as infarction, aneurysm, mitral regurgitation, and ventricular septal defects, together with the presence of thrombus can be detected as well.

Dilated cardiomyopathy is another common cause of heart failure. In addition to precise quantification of systolic left ventricular function, cardiac MRI can reveal any dilatation to cardiac chambers, especially the ventricles. It also detects eccentric hypertrophy, presence of thrombus, and functional valvular dysfunction and can help exclude coronary artery disease and infiltration.

Differentiation of ischemic left ventricular dysfunction from idiopathic dilated cardiomyopathy can be difficult, but it has important therapeutic and prognostic implications.17 Ischemic patients have a poor prognosis and benefit from standard secondary preventive measures and revascularization. Exclusion of secondary causes, accurate phenotyping, and family screening are important steps in early diagnoses of idiopathic dilated cardiomyopathy. Late gadolinium enhancement is not seen in most (60%) patients with dilated cardiomyopathy, though in 28% of cases, it may be seen in the mid-myocardium in a noncoronary pattern. Ischemic-type hyperenhancement is seen in 12% of dilated cardiomyopathy patients.17

Clinical differentiation of restrictive cardiomyopathy from constrictive pericarditis has been a major diagnostic issue. Constrictive pericarditis requires surgical treatment and is usually curable. Restrictive cardiomyopathy, on the other hand, often responds unsatisfactorily to medical therapy and may require cardiac transplant.

Restrictive cardiomyopathy is a rare cause of heart failure. It is characterized by ventricles with normal or reduced volume, preserved systolic left ventricular function, and bi-atrial enlargement. Ventricular filling is impaired with restrictive physiology (Figure 3). Cardiac MRI can measure notable physiological parameters, such as the increased early filling velocity, decreased atrial filling velocity, and decreased deceleration time.

Constriction is associated with an elongated and narrow right ventricle, abnormal motion of a sigmoid-shaped interventricular septum, abnormal cardiac filling, and pericardial thickening.18 Pericardial thickening is the hallmark of constriction, and it can be seen clearly on spin- and gradient-echo MRI. Normal pericardial thickness excludes constriction with reasonable accuracy. The attenuated second peak of caval flow can be demonstrated with velocity mapping.

Hypertrophic cardiomyopathy is the most frequently occurring cardiomyopathy. It can present at any age with features of heart failure due to diastolic dysfunction. Cardiac MRI can define the presence, distribution, and severity of hypertrophy precisely. It is especially useful for detecting unusual distribution of myocardial hypertrophy in variant forms of the disease such as apical cardiomyopathy. The modality provides information on systolic and diastolic function, mitral valve status, coronary arteries, and flow dynamics of left ventricular outflow obstruction.

Almost all patients with hyperenhancement will show involvement at the junction of interventricular septum and right ventricle free wall. Delayed enhancement demonstrates patchy, multifocal subendocardial fibrosis and its extent, which is linked to the risk of sudden death, left ventricular dilatation, and heart failure. Serial cardiac MRI can be used to identify the functional and anatomic consequences of septal resection and ablation. Secondary causes of hypertrophy, such as coarctation and aortic stenosis, can be excluded with confidence. Cardiac MRI will also help differentiate hypertrophy from amyloidosis, Fabry's disease, and athletic heart.19

Cardiac MRI is also useful for other conditions:

. This is a noncaseating granulomatous, multiorgan disorder of unknown etiology that affects the heart. Its involvement is detected in 30% of heart failure patients at autopsy, though it is clinically evident in fewer than 5% of cases. Sudden death may be its initial clinical presentation, and early detection is important. Current diagnostic tools are insufficiently sensitive to detect early cardiac involvement. Gadolinium-enhanced cardiac MRI demonstrates increased signal intensity in the mid-myocardial wall or epicardium and, rarely, in the subendocardium or transmural wall. Sarcoid granulomatous involvement of the myocardium can be detected by cardiac MRI and response to therapy monitored.

. Cardiac involvement is common in primary amyloidosis, causing restrictive ventricular dysfunction. Hypertrophied left ventricle with normal or diminished contraction can be demonstrated by CMR. Hyperenhancement is usually diffuse. Thickening of the right atrial wall and atrial septum is highly suggestive of amyloid infiltration.

. Heart failure caused by iron overload in hemochromatosis or transfusion induced in patients with severe inherited anemias is often overlooked. Myocardial iron causes signal loss on gradient-echo images, which can be used to assess the degree and distribution. Furthermore, the amount of iron in myocardium can be quantified using myocardial T2 value. Cardiac MRI is useful for evaluating different chelation regimes, while serial scans can monitor therapeutic response.

. Untreated valvular heart disease is a common precursor of heart failure. Although echocardiography remains the prime investigation for diagnosis and timing intervention, cardiac MRI plays a complementary role in its assessment. Direct visualization of normal valves is difficult on MRI due to limited temporal resolution, but abnormal valves can be visualized directly.20 Cine MR can detect the presence of valvular stenosis and regurgitation, which is depicted by signal void owing to turbulent flow. Velocity mapping can quantify the regurgitant volume and fraction precisely. This can be very useful when timing surgery in equivocal cases. Peak flow velocity in valvular stenosis can be measured, and the effect of valve lesions on volume, mass, and ventricular function quantified.

. Diagnosis is difficult due to variable clinical presentation. Contrast-enhanced MRI localizes and visualizes the activity and extent of inflammation,both in acute myocarditis and also during the course of the disease (Figure 4).

In summary, cardiac MRI has proven to be an accurate, noninvasive imaging method for assessments of cardiac function. Imaging an organ that is continually moving is undoubtedly a challenge, but achieving this enables the all-important functional evaluation to be performed.

Cardiac MRI techniques have undergone revolutionary changes over the past few years that have made it possible to obtain good-quality images. The modality now provides a comprehensive assessment of the heart's morphology and function, coronary flow, myocardial perfusion, and viability in a single examination. Cost, availability, and expertise, however, continue to limit its wider use in clinical practice.

DR. SATHANANTHAN and DR. LAKSHMAN are international training fellows in cardiology, DR. REID is a medical physicist, and PROF. SIVANANTHAN is a consultant in cardiac imaging and intervention in the department of cardiology at The General Infirmary in Leeds, U.K.

Tendera. M. Epidemiology, treatment, and guidelines for the treatment of heart failure in Europe. Europ Heart J Suppl 2005;7:J5-J9.

Hunt SA, Baker DW, Chin MH, et al. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to revise the 1995 Guidelines for the Evaluation and Management of Heart Failure). Circulation 2001;104(24):2996-3007.

Remme WJ, Swedberg K. Guidelines for the diagnosis and treatment of chronic heart failure: Task force for the diagnosis and treatment of chronic heart failure of the European Society of Cardiology. Europ Heart J 2001;22(7):1527-1560.

Stewart S, MacIntyre K, Hole DJ, et al. More 'malignant' than cancer? Five-year survival following a first admission for heart failure. Europ J Heart Fail 2001;3(3):315-322.

McMurray JJ, Stewart S. Epidemiology, aetiology, and prognosis of heart failure. Heart 2000:83(5);596-602.

Alfakih K, Thiele H, Plein S, et al. Comparison of right ventricular volume measurement between segmented k-space gradient-echo and steady-state free precession magnetic resonance imaging. J Magn Reson Imaging 2002;16(3):253-258.

Alfakih K, Plein S, Thiele H, et al. Normal human left and right ventricular dimensions for MRI as assessed by turbo gradient echo and steady-state free precession imaging sequences. J Magn Reson Imaging 2003;17(3):323-329.

Alfakih K, Plein S, Bloomer T, et al. Comparison of right ventricular volume measurements between axial and short axis orientation using steady-state free precession magnetic resonance imaging. J Magn Reson Imaging 2003;18(1):25-32.

Alfakih K, Walters K, Jones T, et al. New gender-specific partition values for ECG criteria of left ventricular hypertrophy: recalibration by cardiac MRI. Hypertension 2004;44(2):175-179.

Alfakih K, Reid S, Jones T, Sivananthan M. Assessment of ventricular function and mass by cardiac magnetic resonance imaging. Europ Radiol 2004;14(10):1813-1822.

Alfakih K, Bloomer T, Bainbridge S, et al. Comparison of left ventricular mass between two-dimensional echocardiography, using fundamental and harmonic imaging and cardiac MRI in patients with hypertension. Europ J Radiol 2004;52(2):103-109.

Messroghli DR, Bainbridge GJ, Alfakih K, et al. Assessment of regional left ventricular function: accuracy and reproducibility of positioning standard short-axis sections in cardiac MR imaging. Radiology 2005;235(1):229-236.

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Plein S, Greenwood JP, Ridgway JP, et al. Assessment of non-ST-segment elevation acute coronary syndromes with cardiac magnetic resonance imaging. J Am Coll Cardiol 2004;44(11):2173-2181.

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Articles

Heart failure is a common disorder with high morbidity and mortality. It is the only major cardiovascular disease whose prevalence and incidence are not only on the increase but predicted to reach epidemic proportions.

Periyasamy Pillai Sathananthan, MD

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