Role of Cardiovascular Ultrasound in the Evaluation of Obese Subjects.

Obesity represents a worldwide increasing health problem. Obesity, through complex and not fully understood pathogenetic mechanisms, induces different structural and functional changes of left heart chambers, right heart chambers, and arteries. Ultrasound techniques are the first choice for a comprehensive assessment of the cardiovascular adaptation to obesity. This review summarizes the up-to-date literature on the topic, with particular focus on the main clinical studies, which range over different cardiovascular adaptations to obesity, namely left ventricular mass, diastolic function, right ventricle structure and function, arterial stiffness, and intima-media thickness. Also, the importance of epicardial fat and of the degree of obesity is described. Finally, the role of weight loss and bariatric surgery and the study of cardiovascular obesity-induced abnormalities in children and adolescent are discussed.

INTRODUCTION

Obesity is a global health problem, which is still enlarging and involving new developing countries. In the USA, about 34% of adults are overweight and 18% are obese.[1] In China, 25% of the population is overweight.[2] According to the criteria of the National Institute of Health, obesity is defined as a body mass index (BMI) >30 kg/m2 and morbid obesity as a BMI >40 kg/m2.

Obesity is an independent risk factor for coronary heart disease (CHD) and promotes the development of arterial hypertension, diabetes and dyslipidemia. In a meta-analysis including 21 studies and more than 300,000 subject, Borges et al. showed that excessive weight was an independent risk factor for CHD, independent of blood pressure and cholesterol levels.[3] Obesity was also found to be an independent risk factor for all-cause mortality in the Framingham Heart Study, with a 30-year follow-up;[4] the same result derived from several recent studies.[56] Recent American Heart Association (AHA) Guidelines for the Management of Overweight and Obesity in Adults stated peremptorily that that the greater the BMI, the higher the risk of fatal and non-fatal CHD.[7]

Obesity causes a variety of changes in structure and function both in the heart and in the arteries. It is associated with increase in total blood volume, due to a higher oxygen consumption and higher metabolic demand. Adiponectin, leptin, and insulin resistance contribute to the cardiovascular abnormalities seen in obese subjects. Therefore, the increased workload and cardiac output induce several cardiac and vascular changes, which are explained in the review. Figure 1 shows an example of comprehensive cardiovascular evaluation by ultrasound techniques.

Figure 1

Cardiac (a) and Carotid Artery (b) changes in structure and function provoked by obesity. RWT Relative Wall Thickness, LVM Left Ventricular Mass, LAD Left atrium dimension, RVD Right ventricle dimension, IMT Intima-Media Thickness

LEFT VENTRICULAR REMODELING ASSOCIATED WITH OBESITY

Obesity promotes hemodynamic changes, i.e. increased cardiac output and lower peripheral vascular resistance, in absence of overt hypertension.[8] Increased cardiac output, with little changes of heart rate, leads to left ventricle (LV) remodeling. About 60% of obese patients suffer from hypertension; in these subjects, peripheral vascular resistance is lower than vascular resistance in lean hypertensive patients.[9] The high cardiac output leads to LV dilatation, thickening, and dysfunction.

In the 1980s, several studies suggested that obesity induces eccentric left ventricular hypertrophy (LVH), mainly due to the volume overload.[10] This paradigm has been reversed by more recent studies, in which it appears that, in obese subjects, LV concentric remodeling and concentric hypertrophy occur more often than eccentric hypertrophy.[1112]

It is accepted nowadays that in obese subjects, LV mass is normalized for height to the power of 2.7.[13] This allometric relation reflects the association of 3-dimensional (3D) LV mass and height. Although 3D echocardiography and cardiac magnetic resonance (CMR) are superior to 2-dimensional (2D) echocardiography, LV mass can be accurately estimated by the equation, developed by Devereux et al[14]:

0.8 × 1.04 × [(LVDd + LVPWTd. + IVSTd)3 – LVDd3] + 0.6

where LVDd is the LV diastolic dimension, LVPWTd is the LV posterior wall diastolic thickness, and IVSTd is the interventricular septum diastolic thickness.

Taking into account LV mass and relative wall thickness (RWT) Ganau et al. described four different geometrical patterns of cardiac remodeling in hypertensive patients: Normal geometry, LV concentric remodeling, LV concentric hypertrophy, and LV eccentric hypertrophy.[14] Recently Khouri et al. proposed a four-tiered classification of LV hypertrophy, based on CMR imaging of patients enrolled in the Dallas Heart Study. They classified LV remodeling into magnification, eccentric LV hypertrophy, concentric LV hypertrophy, and thick/dilated LV hypertrophy.[15]

It is well documented nowadays the negative prognostic impact of LV hypertrophy in terms of major cardiovascular events, including stroke and myocardial infarction, and increased total mortality.[1617] Because of the low sensitivity of electrocardiography, it is crucial to identify LV hypertrophy correctly by means of echocardiography.

SUBCLINICAL SYSTOLIC DYSFUNCTION IN OBESE SUBJECTS

In almost all the studies currently available in the literature, left ventricular ejection fraction (LVEF) was normal or increased in all obesity classes, apart from cardiac output and workload.[1819] Nevertheless, recent studies highlighted the subclinical systolic dysfunction though preserved LVEF, using new echocardiographic techniques, namely tissue Doppler imaging (TDI), strain rate imaging (SRI), and speckle tracking. Di Bello et al. demonstrated that strain and strain rate analysis allowed the assessment of systolic structural and functional abnormalities at a preclinical stage.[20] Other studies showed that obese patients had lower values of strain rates, of torsion with normal LVEF, compared with lean subjects.[21222324]

DIASTOLIC FUNCTION AND LEFT ATRIAL REMODELING IN OBESE SUBJECTS

Several studies investigated the diastolic function in obese patients. It must be underlined that it is difficult to estimate the impact of obesity itself on diastolic filling process, because most of the obese patients suffer from hypertension, and about 30% of them of suffer from diabetes mellitus. What is definitely stated is that there is a linear correlation between BMI and left atrial pressure, expressed by E/Em ratio.[21] Obesity is related to mild diastolic abnormality, increasing with coexisting cardiovascular risk factor and higher BMI.[2526]

Left atrium enlargement is common in LV hypertrophy. McManus et al. demonstrated in a longitudinal study that BMI correlates with both baseline left atrial dimensions and progressive dilation during the follow-up, independent of blood pressure.[27] It is relevant to the observation that left atrium enlargement and dysfunction, in association with obesity, is an important risk factor for the subsequent development of atrial fibrillation. Di Salvo et al., using strain and strain rate techniques, demonstrated that obesity, even in absence of hypertension, is associated with reduced atrial myocardial deformation properties already in childhood.[28]

THE ROLE OF EPICARDIAL FAT

Epicardial fat is present between the epicardium and the parietal pericardium, mostly in obese patient. It is an active fat reservoir that increased the cardiometabolic risk, as other visceral fat storage.[29] Natale et al. observed that epicardial fat reflected carotid arterial stiffness better than the waist circumference, in a large population of hypertensive patients, most of them being obese.[30] Mahabadi et al. showed that pericardial fat was associated with prevalent CVD in sex and age-adjusted models in a cohort of 1267 subjects [OR 1.32, 95% confidence interval (CI) 1.11-1.57; P 0.002].[31] Epicardial fat can be measured accurately by computed tomography (CT) and CMR, but it can also be qualitatively appraised by conventional 2D echocardiography.

RIGHT VENTRICLE REMODELING AND FUNCTION IN OBESE SUBJECTS

Although sleep-disordered breathing (SDB) plays a confounding counterpart, obesity is itself related to right ventricle (RV) remodeling. Few data raised from conventional echocardiography, as the crescent and irregular shape of the RV. Recently, 3D echocardiography and CMR have surmounted, at least in part, these limitations. In the multi-ethnic study on atherosclerosis, enrolling 4127 participants, Chahal et al. showed by CMR imaging that obese patients had greater RV mass, larger RV end-diastolic volume, larger RV stroke volume, and lower RV ejection fraction than lean subjects, independently of LV dimension and hypertension.[32] Sleep apnea disorder and asymptomatic hypoxic nocturnal episodes may have a pathogenetic role in the development of RV hypertrophy in obese subjects.

THE VERY SEVERE OBESITY: THE CONCEPT OF “SUPEROBESITY”

In the past years, the concept of very severe obesity, namely superobesity, has been emphasized. Superobesity is defined as a BMI more than 50 kg/m2. It has been recently demonstrated that superobesity is associated with higher level of insulin resistance and worse cardiac remodeling compared to “simple” morbid obese patients (BMI >40 and <50 kg/m2).[33] Alpert MA stated in the editorial following the former article that “Size Really Does Matter”,[34] introducing the concept that LV remodeling and diastolic abnormalities continuously worsen in a linear fashion, from overweight to severe and very severe obesity.

EFFECT OF WEIGHT LOSS AND BARIATRIC SURGERY

Weight loss is associated with the reduction of LV hypertrophy.[3536] In the study of Shah et al., a 5% weight loss was associated with a 1.3% decrease in LV mass and LV mass-to-volume ratio.

After bariatric surgery, there is evidence not only of favorable LV remodeling, but also of RV remodeling. In a recent meta-analysis, Cuspidi et al. observed, in a pooled population of 1022 obese subjects with preserved systolic function included in 23 studies, that bariatric procedures induced a decrease in LV mass and RWT, an improvement of LV diastolic function, and a decrease in left atrium diameter without changes in LVEF.[37]

OBESITY-INDUCED VASCULAR ABNORMALITIES

During a first clinical evaluation of obese patients, it is important to evaluate not only the contingent LV and RV remodeling, diastolic function, but it is also essential to study the vascular arterial tree, which can be prematurely damaged by obesity and associated cardiovascular risk factors, as dyslipidemia and insulin resistance. Megias-Rangil et al. recently showed, in a population of 194 obese patients, that more than half of the obese patients have higher intima-media thickness (IMT) and higher arterial stiffness compared with lean subjects.[38] Detection of IMT and arterial stiffness plays an important role in cardiovascular risk stratification in obese patients. It has been observed that parameters of central obesity (e.g., waist circumference, waist-to-hip ratio, waist-to-height ratio) are more closely associated with aortic stiffness than a measure of general obesity like BMI.[39]

CARDIAC REMODELING IN OBESE CHILDREN AND ADOLESCENT

Obesity in children is associated with changes in cardiac structure and function, similar to those seen in obese adult subjects. In particular, there is an increased left ventricular mass, increased left ventricular and left atrial diameter, greater epicardial fat, and subclinical systolic and diastolic dysfunction.[404142] Childhood obesity is also associated with carotid intima-media thickening and high arterial stiffness.[4344]

LIMITATIONS OF ULTRASOUND IN OBESE PATIENTS: THE ROLE OF CONTRAST ECHOCARDIOGRAPHY

At the present time, new cardiac imaging techniques can identify early subclinical LV and RV damage related to obesity, but in many cases fat impedance leads to poor acoustic window.[4546] Before sending an obese patient for a CMR, which is expensive and difficult in severe obese patients due to limited bore size of the machine, an attempt with contrast-echocardiography should be done, according to the European Association of Cardiovascular Imaging (EACVI).[47] Contrast is useful to assess LV structure, LVEF and it can be injected during a stress echocardiography to assess segmental wall motion and thickening at rest and stress.[4849] [Figure 2].

Figure 2

Left Ventricle view before and after contrast injection in an obese subject with a poor acoustic window

CONCLUSION

Obesity is a worsening epidemic in western and developing countries, leading to increasing morbidity and mortality. Echocardiography and vascular ultrasound can identify accurately early obesity-induced abnormalities, such as LV hypertrophy, subclinical LV dysfunction, and preclinical atherosclerosis. These findings may help the clinician to encourage lifestyle modification and weight loss in obese patients, with a favorable impact on the prognosis.