Accreditation Statement:

The American Society of Echocardiography is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The American Society of Echocardiography designates this educational activity for a maximum of 1 AMA PRA Category 1 Credit ™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

ARDMS and CCI recognize ASE’s certificates and have agreed to honor the credit hours toward their registry requirements for sonographers.

The American Society of Echocardiography is committed to ensuring that its educational mission and all sponsored educational programs are not influenced by the special interests of any corporation or individual, and its mandate is to retain only those authors whose financial interests can be effectively resolved to maintain the goals and educational integrity of the activity. While a monetary or professional affiliation with a corporation does not necessarily influence an author’s presentation, the Essential Areas and policies of the ACCME require that any relationships that could possibly conflict with the educational value of the activity be resolved prior to publication and disclosed to the audience. Disclosures of faculty and commercial support relationships, if any, have been indicated.

Target Audience:

This activity is designed for all cardiovascular physicians and cardiac sonographers with a primary interest and knowledge base in the field of echocardiography; in addition, residents, researchers, clinicians, intensivists, and other medical professionals with a specific interest in cardiac ultrasound will find this activity beneficial.

Target Audience:

This activity is designed for all cardiovascular physicians and cardiac sonographers with a primary interest and knowledge base in the field of echocardiography; in addition, residents, researchers, clinicians, intensivists, and other medical professionals with a specific interest in cardiac ultrasound will find this activity beneficial.

Objectives:

Upon completing the reading of this article, the participants will better be able to:

• 1.
  

  Recognize non-valvular physiologic and pathologic conditions that exhibit left ventricular hypertrophy (LVH) as a key cardiac finding.

  
  
• 2.
  

  Describe the echocardiographic findings unique to various etiologies of LVH.

  
  
• 3.
  

  Differentiate between different physiologic and pathologic conditions using standard and advanced echocardiographic techniques.

  
  
• 4.
  

  Recognize that integrating echocardiography with clinical history is frequently necessary to distinguish various etiologies of LVH.

Disclosures:

The authors of this article reported no actual or potential conflicts of interest in relation to this activity.

The ASE staff, members of the ASE ACCME/CME Committee and article reviewers who were involved in the planning and development of this activity reported no actual or potential conflicts of interest: Chelsea Flowers; Rebecca T. Hahn, MD, FASE; Cathy Kerr; Priscilla P. Peters, BA, RDCS, FASE; and Cheryl Williams.

The following members of the JASE Editorial Staff reported no actual or potential conflicts of interest in relation to this activity: Julius M. Gardin, MD, FASE; Jonathan R. Lindner, MD, FASE; Victor Mor-Avi, PhD, FASE; Sherif Nagueh, MD, FASE; Alan S. Pearlman, MD, FASE; J. Geoffrey Stevenson, MD, FASE; and Alan D. Waggoner, MHS, RDCS.

Estimated Time to Complete This Activity: 1 hour

Athlete’s Heart

In athletes, regular exercise induces symmetric LV hypertrophy, which is considered a physiologic adaptive process to the demanded increase in stroke volume. In addition, the left ventricle starts to dilate slightly. Many studies suggest that specific morphologic adaptations and changes in LV mass result from systematic training in different sports disciplines. The most extreme increases in LV wall thickness have been observed in elite athletes training in rowing and cycling, whereas athletes participating in ultra-endurance sports (such as triathlon) paradoxically show more modest alterations in cardiac dimensions and hypertrophy. Of note, racial differences in LV wall thickness may also have an impact, as the somewhat greater septal dimensions in some black athletes may generate false-positive diagnoses of hypertrophic cardiomyopathy (HCM). In general, this type of physiologic hypertrophy is not associated with myocardial fibrosis or fiber disarray, as it is observed frequently in pathologic LV hypertrophy. On echocardiography, end-diastolic wall thickness rarely exceeds 14 mm, and the hypertrophy is symmetric, with no LV outflow tract obstruction. In addition, both systolic global function and diastolic indexes are normal. These echocardiographic findings together with a history of longstanding regular exercise render the diagnosis of athlete’s heart relatively easy. The scenario changes if the same patient presents with an additional history of moderate hypertension. More advanced echocardiographic techniques are necessary then to distinguish between physiologic and pathologic hypertrophy. Typically, peak myocardial systolic velocities and strain rate are normal or even supranormal in physiologically hypertrophied hearts. These findings are in contrast to hypertensive heart disease, in which especially longitudinal myocardial systolic velocities and strain rate are reduced.

Mild forms of HCM may also be difficult to distinguish from physiologic hypertrophy in athletes. This has significant implications because sudden cardiac death in an athlete with undiagnosed HCM is a preventable tragedy. Normal diastolic function by echocardiography typically distinguishes athletes with physiologic hypertrophy from those with HCM in whom diastolic function is abnormal. In addition, electrocardiography may be helpful in screening athletes and typically has abnormal results in those with HCM.

Idiopathic Hypertrophic Obstructive and Nonobstructive Cardiomyopathy

In idiopathic HCM, mutations in sarcomeric protein genes underlie the typical histopathologic finding of myocyte disarray. This fiber disarray, in combination with disturbed energy homoeostasis, is closely associated with a characteristic hypertrophic transformation of the left ventricle. The diagnosis of HCM is made in up to 25% of patients initially classified as having “unclear LV hypertrophy.” Most patients with HCM exhibit an asymmetric pattern of hypertrophy, with a predilection for the interventricular septum and the LV anterior wall; concentric, isolated apical, and other atypical distributions, however, have also been described. An unexplained maximum end-diastolic LV wall thickness > 15 mm in any myocardial segment accompanied by a normal wall thickness (<12 mm) in other segments and a nondilated left ventricle is suspicious for the diagnosis of idiopathic HCM ( Video 1 ; view video clip online). In about 25% of these patients, dynamic LV outflow tract obstruction (ie, a resting gradient > 30 mm Hg) is present, caused by the contact between the anterior mitral valve leaflet and the thickened interventricular septum during systole. The typical echocardiographic finding is a systolic anterior movement of the anterior mitral valve, which is a key to the diagnosis of hypertrophic obstructive cardiomyopathy. This systolic anterior movement can be visualized with M-mode and 2-dimensional echocardiography. In addition, most patients with dynamic outflow tract obstruction exhibit posteriorly directed jets of mitral regurgitation caused by insufficient leaflet apposition ( Figure 1 ). In some rare cases, the obstruction is not in the LV outflow tract but rather at the midventricular level. This causes a midventricular gradient, which can be detected by Doppler echocardiography.

(Left) Four-chamber view from a patient with hypertrophic obstructive cardiomyopathy. The thickened interventricular septum contrasts with a thin lateral wall. The arrow indicates the posteriorly directed jet of mitral regurgitation caused by the failure of leaflet apposition due to the dynamic gradient. (Right) Typical strain rate and strain curve recorded over 1 heart cycle and extracted from the basal septum. Note that systolic strain is reduced to 7%. In the strain rate curve, a small second peak can be detected shortly after aortic valve closure (AVC) indicating replacement fibrosis (double peak sign).

Global LV systolic function measured by ejection fraction is normal or increased at rest in most patients, but regional function (particularly in segments in which hypertrophy is most prominent) may be reduced. Importantly, this often markedly reduced longitudinal function of the thickened segments may easily and reliably be visualized using strain rate imaging techniques. In addition, the replacement fibrosis sometimes found within the thick segments by late enhancement cardiac magnetic resonance imaging produces a typical pattern in the regional strain rate curve with a second peak shortly after aortic valve closure (the double peak sign). Thus, using the more advanced techniques, the reduction of regional myocardial function and the presence of myocardial fibrosis can be detected and subsequently used for specific diagnosis ( Figure 1 ). Concomitant abnormalities of diastolic function in hypertrophic obstructive cardiomyopathy and hypertrophic nonobstructive cardiomyopathy include inadequate LV relaxation and compliance and may frequently be detected by echocardiography. However, diastolic function abnormalities are nonspecific and usually not helpful in guiding the differential diagnosis.

Hypertension

Longstanding systemic hypertension results in a permanent pressure overload of the left ventricle. In patients with hypertension, the LV myocardium compensates for this increased systolic wall stress by developing hypertrophy. A large spectrum of LV geometric changes is observed in patients with hypertension, including concentric remodeling (normal LV mass and increased relative wall thickness), concentric hypertrophy (increased LV mass and increased relative wall thickness), and eccentric hypertrophy (increased LV mass and normal relative wall thickness). In principle, the development of LV hypertrophy is multifactorial, with studies suggesting associations with age, gender, race, body mass index, and neurohormonal stimulation. Regional LV wall stress is inhomogeneous according to the irregular curvature within the nonspherical left ventricle. Because of the largest local radius of the ventricular curvature at the basal septum, wall stress is highest there. Because hypertrophy is directly related to wall stress, the basal septal segment usually develops a characteristic bulge. In newly diagnosed patients with hypertension, this basal septal bulge is especially prominent because the rest of the left ventricle is not yet hypertrophic ( Figure 2 ). Regional systolic myocardial function in this bulge (assessed by strain rate imaging) is only slightly reduced. At this early stage, especially the deformation rate (peak systolic strain rate) and not so much the amount of deformation (systolic strain) is reduced as the earliest sign for hypertensive heart disease. These typical features assessed by advanced echocardiography are very helpful for the distinction from athletes’ heart (in which the peak systolic strain rate is supernormal) and also from the HCM bulge (in which systolic strain is markedly reduced). In general, a history of elevated blood pressure in combination with echocardiographic LV hypertrophy leads easily to the diagnosis of hypertensive heart disease. However, in patients who have had infrequent medical care with few records of blood pressure or in whom blood pressure elevation is not severe, strain rate imaging is useful for unmasking the reduced regional longitudinal function associated with hypertensive heart disease. Global LV systolic function assessed by ejection fraction is usually normal but may become compromised in end-stage disease after longstanding untreated hypertension. Most if not all patients with hypertension develop diastolic filling abnormalities very early in the disease progression.

Four-chamber view from a patient with essential arterial hypertension. The typical concentric LV hypertrophy with a prominent basal septal bulge (arrow) is shown.

Amyloidosis

Amyloidosis is a systemic disease characterized by the deposition of interstitial amyloid fibrils in various organs, including the heart. Nine percent of patients with formerly unspecified LV hypertrophy end up with diagnoses of amyloidosis. Cardiac involvement is most severe in primary amyloidosis, in which LV wall thickness is increased by light-chain amyloid protein deposition. More than 50% of all amyloidosis-related deaths are attributable to cardiac infiltration. In echocardiography, the most distinguished feature is concentric LV hypertrophy, with a sparkling, granular myocardial texture ( Video 2 ; view video clip online). However, this myocardial texture is not specific for amyloidosis and can be seen also in HCM and other hypertrophic diseases. LV outflow tract obstruction is never seen, and the end-diastolic wall thickness rarely exceeds 14 mm. Most of these patients present with localized or concentric pericardial effusion ( Figure 3 ). Cardiac manifestation of the amyloid deposition is described as the “stiff heart syndrome,” with early impairment of diastolic function and relatively preserved global systolic function until late in the disease. Thus, most patients show some degree of diastolic relaxation abnormalities, but the restrictive filling pattern is found only in the advanced stages of the disease. This diastolic abnormality with an increase of diastolic filling pressure also causes dilatation of the left atrium. Often, however, it remains difficult to distinguish cardiac amyloidosis from other hypertrophic diseases despite adequate registration of these established echocardiographic features. Importantly, most patients with hypertrophic amyloidosis present with low QRS voltage on electrocardiography because of the interstitial amyloid protein.

(Left) Four-chamber view from a patient with cardiac amyloidosis. Concentric LV hypertrophy with sparkling, granular myocardial texture and a small epicardial effusion (arrow) is shown. (Right) Typical strain rate curve recorded over 1 heart cycle and extracted from the septum. Note that systolic strain rate peaks already very early during the isovolumetric contraction period (white arrow) and the systolic longitudinal strain rate is severely depressed (black arrow) . AVC , Aortic valve closure; AVO , aortic valve opening.

Again, the additional assessment of regional myocardial function adds to diagnostic accuracy. Typically, longitudinal LV function assessed by strain rate imaging is markedly reduced. Interestingly, systolic strain rate peaks very early during the isovolumetric contraction period, and systolic longitudinal strain is very low ( Figure 3 ). In marked difference to all other hypertrophic diseases, cardiac amyloidosis is the disease in which longitudinal function is most homogeneously reduced and is usually <10%. Only the apical LV segments occasionally present with preserved longitudinal function. In a recent prospective study of patients with biopsy-proven light-chain amyloidosis, tissue velocity, strain, and strain rate were determined at the base, mid, and apical segments in two apical views. A significant difference in measurements was seen between these levels, but on multivariate analysis, only mean LV basal strain was an independent predictor of both cardiac and overall deaths.

In some patients (especially in very early disease stages), the diagnosis of cardiac amyloidosis remains equivocal even after careful echocardiographic examination and may thus be confirmed by endomyocardial biopsy.

Friedreich’s Ataxia

Friedreich’s ataxia is an autosomal recessive neurodegenerative disease caused by an intronic GAA triplet repeat expansion. This leads to a defect in the gene encoding for the mitochondrial protein frataxin, resulting in mitochondrial dysfunction. In the heart, this mitochondrial respiratory dysfunction leads to cellular hypertrophy, diffuse fibrosis, and focal myocardial necrosis. Myocardial involvement in Friedreich’s ataxia is well documented, with the most common cardiac finding being LV hypertrophy. Clinical signs of cardiac involvement typically occur late in the course of the disease, but heart failure accounts for >50% of deaths from this disease. The typical pattern is that of concentric LV hypertrophy with an end-diastolic wall thickness of no more than 15 mm and no outflow tract obstruction. In addition, a sparkling, granular texture comparable with that of cardiac amyloidosis is seen also in most patients with Friedreich’s ataxia ( Figure 4 , Video 3 ; view video clip online). Global systolic function is preserved in most patients, and only end-stage patients develop reduced ejection fractions with global hypokinesia and slightly dilated left ventricles. Of note, because the increase in LV wall thickness develops quite rapidly, most patients with hypertrophy have normal diastolic function. Assessment of regional function by strain rate imaging reveals only mildly reduced longitudinal parameters ( Figure 4 ). The two latter features may be used to discern Friedreich’s ataxia from cardiac amyloidosis. Electrocardiography is usually not diagnostic helpful because both signs for LV hypertrophy and low voltage on electrocardiography are infrequent.

(Left) Four-chamber view from a patient with Friedreich’s ataxia. Concentric LV hypertrophy and sparkling, granular texture of the myocardium (arrow) , similar to Figure 3 . (Right) Typical strain rate curve recorded over 1 heart cycle and extracted from the septum. In contrast to Figure 3 , systolic strain rate (−1.1 s ⁻¹ ) is only slightly reduced (normal, −1.3 s ⁻¹ ). AVC , Aortic valve closure.

The combination of neurologic ataxia and HCM is pathognomonic for the disease. However, in every patient suspected for Friedreich’s ataxia, the diagnosis should be confirmed by genetic blood testing to guide counseling of relatives.