imaging diagnosis of right ventricle involvement in chagas...

Review ArticleImaging Diagnosis of Right Ventricle Involvement inChagas Cardiomyopathy

MinnaM D Romano Henrique T Moreira Andreacute SchmidtBenedito Carlos Maciel and Joseacute Antocircnio Marin-Neto

Medical School of Ribeirao Preto University of Sao Paulo Ribeirao Preto SP Brazil

Correspondence should be addressed to Minna M D Romano minnaromanogmailcom

Received 9 June 2017 Accepted 24 July 2017 Published 27 August 2017

Academic Editor Kristina Haugaa

Copyright copy 2017 Minna M D Romano et al This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

Right ventricle (RV) is considered a neglected chamber in cardiology and knowledge about its role in cardiac function was mostlyfocused on ventricular interdependence However progress on the understanding of myocardium diseases primarily involving theRV led to a better comprehension of its role in health and disease In Chagas disease (CD) there is direct evidence from both basicand clinical research of profound structural RV abnormalities However clinical detection of these abnormalities is hindered bytechnical limitations of imaging diagnostic tools Echocardiography has been a widespread and low-cost option for the study ofpatients with CD but when applied to the RV assessment faces difficulties such as the absence of a geometrical shape to representthis cavity More recently the technique has evolved to a focused guided RV imaging and myocardial deformation analysis Alsocardiacmagnetic resonance (CMR) has been introduced as a gold standardmethod to evaluate RV cavity volumes CMR advantagesinclude precise quantitative analyses of both LV and RV volumes and its ability to perform myocardium tissue characterization toidentify areas of scar and edema Evolution of these cardiac diagnostic techniques opened a newpath to explore the pathophysiologyof RV dysfunction in CD

1 Introduction

Historically physiology concepts about heart function con-sidered the right ventricle as a kind of almost perfunctorychamber although knowledge about ventricle interdepen-dence was well recognized decades ago [1] Weber et al inan outstanding publication of 1981 in this field postulated thefollowing

However because the right and left ventriclesare aligned in series and mechanically coupleda perturbation in the mechanical events of oneventricle will influence the behavior of the otherventricle and in nonsteady state conditions theoutput of the two ventricles may not be balancedEventually however a steady state of balancedoutputs must occur if pulmonary or systemicvenous congestion is to be avoided [1]

Diastolic interplay between ventricles is easy readilyunderstandable mainly considering the function of peri-cardium as the common covering layer for both ventriclesHowever although the presence of pericardium accentuatesthis interaction animal experimental models with the peri-cardium excised showed that the diastolic interplay was stillpresent [2] There is also a systolic interplay so that duringsystole the pressure in one ventricle will influence the systolicpressure developed in the other The systolic interplay hasbeen primarily demonstrated as the predominant influencethe left ventricle exerts upon the right ventricle This isbecause the opposite effect of lower systolic pressure of rightventricle influencing left ventricle performance is usuallyminimized under normal physiologic conditions As theinterventricular septum plays an important role in the inter-ventricular pressure relationship its function was assessedin classic animal experiments with total destruction of RVfree wall but with maintenance of septum presence [3] and

HindawiBioMed Research InternationalVolume 2017 Article ID 3820191 14 pageshttpsdoiorg10115520173820191

2 BioMed Research International

in contrast in experimental models of septum dysfunctionbecause of infarction [4]

Based on these physiologic aspects and adding to the factthat many of the studies were designed on a volume-pressurerelation basis it is possible to understand why cardiologyscience neglected theRVas a ldquosecondary chamberrdquo or a ldquopass-ing chamberrdquo [5] Nonetheless knowledge about primarymyocardial conditions affecting the RV without concomitantpressure overload of this chamber as inUhlrsquos anomaly andRVdysplasia reinforces the need of other theories to explain thereal influence of right ventricular function in cardiovascularphysiology The fact that RV dysplasia includes a phase ofright-sided cardiac failure beyond the arrhythmic clinicalcomplications gives an insight to the fact that advanced RVmuscle impairment can be clinically significant and directlyleads to intrinsic heart failure syndrome [6]

There is evidence that CD causes a peculiar right ventricleinvolvement first because evolution of the disease to heartfailure usually includes prominent right heart failure symp-toms in absence of or with only mild pulmonary congestion[7 8] second because there is direct evidence of myocardialdamage of the right ventricle in human myocardial biopsiesand postmortem studies as well as in animal experimentalmodels of T cruzi infection and finally because there is aproportion of patients with early and isolated right ventricledysfunction when evaluated by different cardiac imagemeth-ods [9 10]

However exploring the right ventricle with imagingdiagnostic tools is still a challengeThe accumulated evidenceabout ventricular systolic function inmost diseases is derivedfrom echocardiography Two-dimensional echocardiographyneeds geometrical assumptions to estimate ventricular vol-umes and the right ventricle simply does not have a mathe-matically defined geometrical form

This review explores the right ventricle anatomic andfunctional involvement in Chagas cardiomyopathy (CC)while highlighting the contribution of cardiac imaging diag-nostic methods in the field

2 Chagas Cardiomyopathy (CC)

CD was recognized by WHO as one of the worldrsquos 13 mostneglected tropical diseases with a high prevalence of indi-viduals at risk of infection in South and Central Americaand with the highest rates of mortality between all neglecteddiseases [14] Although its prevalence had slightly declinedthrough the last decade it can reach 114 of heart failurecauses in specific endemic regions of Brazil [15] Althoughoriginally confined to poor rural areas of Latin Americamigration movements contributed to spread CD to nonen-demic countries in Europe Canada and USA [16 17]

CD is caused by the T cruzi protozoan infection thatleads in most cases to a myocardial chronic inflammatoryresponse [7] Myocardial damage is probably a result of im-balance between parasite persistence and adverse immune-inflammatory response [18] which result in a broad spectrumof tissue lesions Myocardium disease is characterized bya low-intensity slowly progressive but incessant myocardi-tis which leads to impairment of contractile function and

dilatation of cardiac chambers [7] Histologically there is awidespread destruction of myocardial cells edema diffusefibrosis mononuclear cell infiltration and scarring of theconduction system and the contractile myocardium [11 19](Figure 1) Early stages of the disease are still not fully under-stood but conduction system abnormalities can occur beforemyocardium contractile function impairment [20] Cardiacautonomic dysfunction may also be an early consequenceof the loss of cardiac neuronal parasympathetic activity [21ndash23] Microvascular coronary dysfunction also occurs and itsmechanism is still not well known but is likely to contributeto contractile function damage [24ndash26] Progression of themyocardium damage results in a scenario of widespreadsubstitution by fibrous tissue which is the core of botharrhythmogenesis and heart failure

CD includes an acute and a chronic phase Acute infectionis usually underdiagnosed There is a recent increase ofcases secondary to reactivation from the chronic phase byblood transfusion or transplantation of solid organs andcongenital or oral contaminations [27 28] Most of acutecases run through an asymptomatic clinical course Whensymptoms occur they include fever malaise enlargement ofliver spleen and lymph nodes and subcutaneous localizededema [7] The grade and type of immunological responsehave a key role in controlling parasitemia during acute phaseand permit most of patients to undergo to the chronicclinically silent indeterminate form of disease Howeversome 30 of infected subjects will present symptoms andor signs of cardiac damage 10ndash30 years later [7] Bradycardiaand conduction system abnormalities can occur early in theevolution of disease as well as frequent ventricular ectopicbeats [17 19] Ventricular tachycardia is ominous and can beresponsible for sudden cardiac death even in less advancedstages of the disease [29] Other typical ECG alterationsinclude right bundle branch block and left anterior fascicularbundle block which can be combined [19 30]

Myocardial damage typically causes regional contractiondisturbances in the left ventricle and the virtually pathog-nomonic apical aneurisms [22 31] Global LV dilatationand systolic dysfunction are also often seen as the diseaseprogresses When heart failure supervenes it is usually withbiventricular manifestations and systemic congestion can bemore impressive when compared to pulmonary congestionPatients with cardiac form of CD are seen frequently incardiac units and clinics all around South and CentralAmerica They usually present with heart failure symptomsduring recurrent hospital admissions In many cases symp-toms and signs of systemic congestion are very prominentThey usually complain of lower limbs edema weight gainincrease in abdominal volume and pain associated withhepatomegaly This conspicuous form of right-sided heartfailure presentation was well described since the first reportson clinical CD [32ndash34] and still puts a challenge to treatmentPatients need high doses of diuretics and vasodilators andsometimes the use of intravenous inotropes although it withno proven benefit onmortality is warranted as a symptomatictreatment resource [33]

Because of these peculiar aspects of CD cardiomyopa-thy diagnostic tools capable of detecting early myocardial

BioMed Research International 3

(a) (b) (c)

(d) (e) (f)

p lt 0001p lt 0001

p lt 005

Control 30 100

Days postinfection

0

20

40

60

80

100

120

140

Num

ber o

f mon

onuc

lear

cells

RV

fiel

d

(g)

p lt 0001 p lt 001

p lt 005

Control 30 100

Days postinfection

0

20

40

60

80

100

120

140

Num

ber o

f mon

onuc

lear

cells

LV

fiel

d

(h)

Figure 1 Histological analysis (HE) depicting normal cardiac fibers with regular interstitial space in the right (a) and left (b) ventriclesIn a T cruzi-infected mice with 30 days post-Chagas infection (acute phase) there is an intense and diffuse myocarditis characterized bylymphomononuclear interstitial infiltrate (white arrow) multiple ruptured or unruptured pseudocysts (black arrow) and enlargement of theinterstitial space ((c) and (d)) After 100 days of infection (chronic phase) the number of the lymphomononuclear inflammatory cells becamesignificantly reduced and no parasites are detected ((e) and (f)) In this study the numbers of interstitial mononuclear cells were quantifiedin both right and left ventricles The number of cells was markedly increased at 30 days of infection as compared to 100 days of infectionmostly in the right ventricle ((g) and (h)) Bars = 100 120583m 119899 = 6daygroup HE = Hematoxylin-Eosin stain Adapted from [11] Adapted withpermission from Elsevier license number 4120251034702

involvement in both ventricles can represent a first steptowards an early and effective treatment of these patientsbefore the development of more advanced fibrotic and irre-versible changes

3 Evidence of Right Ventricle Involvement inChagas Disease (CD)

There is considerable evidence showing CC to be quitedifferent from other forms of dilated cardiomyopathy fromthe pathologic standpoint [35] Not only is there a prominent

myocardial cell destruction associated with focally diffusemononuclear cell infiltration but also an intense interstitialfibrosis is seen (Figure 2) surrounding muscle cells andvessels (Figure 3) [12] The process of inflammation andfibrosis is widespread and involves both the right [36] andleft ventricles and has particular predilection for the cardiacconduction system and the apex of left ventricle [35 37]Higuchi et al in a previous study using RV endomyocardiumbiopsies compared ultrastructural changes in CD patientswith different forms of the disease (indeterminate versuscardiac with and without ECG alterations) and did not


p lt 001

p lt 005

p lt 005

NSNSNS

10

8

6

4

2

0

Col

lage

n LV

fiel

d (

)

Col

lage

n RV

fiel

d (

)

Control 100

Days postinfection Days postinfection

4

3

2

1

030 Control 10030

(a)

(b)

Figure 2 Interstitial collagen (Picrosirius red-stained sections) in controls and T cruzi-infected mice (a) The bar graphs show the meanfraction of fibrosis () in both right (left graph) and left ventricles (right graph)There is a tendency towards increased amount of collagen inacute phase (30 dpi) in both ventricles The mean amount of collagen is significantly increased in the RV (600 higher) and LV (62 higher)in chronic phase (100 dpi) (b) Representative images illustrate these results clearly showing that the collagen increase was mainly perimysialBars = 50 120583m 119899 = 6daygroup Adapted from [11] Adapted with permission from Elsevier license number 4120251034702


Normal Chagasrsquo HD

Figure 3 Schematic representation of the myocardial fibrosis patterns in control myocardium (normal) and in chronic Chagasrsquo heart disease(Chagasrsquo HD) From [12] Adapted with permission from Elsevier license number 4120260350349

encounter important differences among them Since thepathological materials for these studies were obtained fromthe RV myocardial tissue and the ultrastructural alterationsdetected were similarly distributed in patients with the differ-ent forms of CD these findings suggest an early involvementof the right ventricle ultrastructure in many patients [38]Other studies with right ventricle biopsies also showed thatmyocardium lesions may be caused by a continuous processalong all forms of the chronic disease and are found evenin early stages of the disease (eg in patients with theindeterminate form of the disease) [39]

The peculiar clinical aspects of Chagas cardiac failuredrove initial research to investigate the real role of rightventricle dysfunction in the disease physiopathology In factprevious studies reported on patients with CD showed thatisolated right ventricle disturbances are frequent occurrences[21 34] It has also been reported that heart failure mortalityin CD is higher when compared to mortality associatedwith heart failure due to ischemic causes or other car-diomyopathies [40 41] Among other possible factors RVdysfunction prevalencemay be responsible for highmortalityof heart failure in chronic CD once as in other causes of heartfailure it has independent prognostic impact [42] It is alsonoteworthy that in cases of reactivation of T cruzi infectionin immune suppressed patients a remarkable degree of RVdilation and systolic dysfunction has been described [43ndash45]

Despite these findings some controversy occurs in theliterature regarding the detection of clinically apparent earlyright ventricle involvement inCC Carrasco et al [46] studied60 subjects using cardiac catheterization and radiologicalcontrast angiography for both RV and LV in patients withdifferent forms of chronic CD and did not find right ventric-ular dysfunction or dilatation in a subgroup (1) of 14 patientswith normal ECG and normal left ventricular function Inthe three other disease severity subgroups composed of(2) normal ECG and abnormal LV function (3) abnormalECG and abnormal LV function without cardiac failuresymptoms and finally (4) abnormal ECG with abnormal LV

function and symptoms of cardiac failure the proportion ofRV dilatationglobal RVEF reductionsegmental wall motionabnormalities was respectively 55064 for group (2)793274 for group (3) and 71100100 for group(4) Evaluating these results under the lens of modernknowledge about the complexity of cardiac imaging methodsin assessing RV function it is plausible to conclude thatthere is a progression of RV disease among patients with thevarious forms of CD even if apparently no abnormalitieswere detected in the early asymptomatic phase of the diseasewith the methods employed In contrast Marin-Neto etal [9] studying RV function with the more accurate andquantitative method of ECG-gated radionuclide angiocar-diography were able to demonstrate in a carefully selectedgroup of patients with the indeterminate form of disease areduction in RVEF despite the presence of preserved LVEFThis investigation rescued the concept of RV early functionalimpairment in patients with CD in line with the pathologicalfindings described above and the clinical manifestationsalready alluded here This was possible due to the inherentfact that radionuclide angiography allowed the concomitantevaluation of both LV and RV After the study of Carrascoet al without known exceptions all studies assessing theventricular function with contrast ventriculography werefocused exclusively on the LV and coronary angiography

The results from the studywith radionuclide angiographycoupled with previous anatomopathologic data already dis-cussed produced the hypothesis that RVmyocardial damagemay be an early and direct pathophysiological consequenceof CC This hypothesis also comprehends the notion thatin a scenario of low vascular pulmonary resistance (ie inthe absence of LV systolic and diastolic dysfunction andits retrograde effects upon the pulmonary circulation) noclinical manifestations of the RV functional impairmentwould be detectable However within this setting of RVearly impairment when the left ventricle dysfunction occurscausing the rise in pulmonary vascular resistance compen-satory mechanisms of the RV achieve their limits From


this moment on right-sided symptoms and signs may thusdominate the clinical expression of heart failure [34]

Mady et al who had already shown right ventricle histo-logic abnormalities in 60 of patients with the indeterminateform of CD [36] also studied them a year later with invasivecardiac catheterization Of note the only hemodynamicabnormality seen in those patients with this form of CD wasthe RV end diastolic pressure elevation [47] In the absence ofany signs of LV dysfunction it would be possible to concludethat the elevated diastolic pressure in the RV chamber mightbe due to the underlying structural abnormalities previouslydetected in the same patients

Several years later various studies using echocardiogra-phy as a noninvasive tool to assess RV geometry and functionshowed mixed results in diverse groups of patients withvarious forms of CD Nunes et al in 2004 using a nonquan-titative echocardiography analysis reported not being able todetect isolated RV dysfunction in a group of subjects in bothearly and later (28 of patients) stages of CC [48] Howeverthis conclusion was based only on a subjective global classi-fication of RV systolic dysfunction Moreover in this studyonly patients with some degree of left ventricle dilatation orsystolic dysfunction were included which per se makes theinvestigational task of finding isolated RV early involvementunfeasible Furtado et al also investigated the prevalence ofRV systolic and diastolic dysfunction including its globalperformance index in a group of 60 subjects without evidenceof cardiac disease by conventional diagnostic methods [49]In contrast to the results of Nunes et al the authors found a26 prevalence of RV systolic dysfunction when using tissueDoppler systolic tricuspid velocity wave (S1015840) In that study noother echo parameters of RV function could differentiate theperformance of patients with indeterminate form CD fromnormal controls Ten years later using speckle tracking as anew methodology echocardiography tool with potential tomeasure myocardium deformity Barbosa et al [50] reportedthat no RV longitudinal strain differences could be detectedbetween patients with indeterminate form CD and normalcontrols

Recently Moreira et al demonstrated in a comparativeinvestigation using cardiac magnetic resonance as a referencemethod that all conventional echocardiographic parametersfor right ventricular assessment studied including TAPSES1015840 of tricuspid annulus fractional area change and rightventricular index of myocardial performance have a verylow sensitivity to detect right ventricular systolic dysfunctionin patients with CD In contrast analysis of right ventric-ular deformation by using two-dimensional speckle track-ing echocardiography yielded a high ability to differentiatepatients with from those without RV systolic dysfunctionThe right ventricular free wall strain had a remarkably highersensitivity in comparison with traditional echocardiographicparameters to identify RV dysfunction [13]

Cardiac magnetic resonance methods have inherentadvantages for the evaluation of RVEF since volumes can bedirectlymeasured instead of being geometrically extrapolated[51] Studying 158 subjects with CD using cardiac magneticresonance Moreira et al described reduced right ventricularejection fraction in 37 of the patients studied [51] Although

usually associated with LV dysfunction isolated early rightventricular dysfunction was also found in a small subset(44) of patients [51] Furthermore right ventricular dys-functionwas independently associated with atrial fibrillation

Based on all exposed data we can conclude that detectionof incipient right ventricle dysfunction is still dependent ontechnical evolution of cardiac diagnosis image tools Andthis concept probably can be extrapolated to any diseasewith a potential to primarily involve the right ventricularmyocardium

The prognostic impact of RV dysfunction in CD is notyet completely explored Nunes et al evaluated 158 subjectsall with left ventricle dilatation and dysfunction during afollow-up of 34 plusmn 23 months The RV dysfunction param-eter evaluated Tei index of ventricular performance was apredictor of mortality [42] These data can be taken as thefirst demonstration of the role of RV dysfunction as a possibleprognostic marker in CC Nevertheless prognostic studieshave still several barriers to transpose One of them is tocompare a new parameter with others previously establishedand this aspect was not correctly tested considering thevalidated Rassi score in CC [52 53] In contrast althoughthe myocardium performance index of right ventricle (Teiindex) was already proven to be able to detect RV dysfunctionin other scenarios [54] in CD this index could not identifyRV involvement in the indeterminate form group of patients[55]

4 Heart Conduction Disturbances inChagas Cardiomyopathy and Its Relation toRV Function

CD frequently affects the heart conduction system and themost frequently found conduction abnormality is right bun-dle branch block (RBBB) often associated with left anteriorfascicle bundle branch block (LAFB) [56] Prevalence ofRBBB varies between T cruzi chronically infected popula-tions from 15 to 40 [17 57] Among 2756 patients enrolledin the BENEFIT trial RBBBwas found in roughly 52 and in35 of cases it was associated with LAFBB This associationwas also reproducible in experimental animal models ofinfection with the T cruzi [19] Histologically these regionsof the cardiac conduction system show chronic fibrosis andprogressive obliteration [37]

It is not clear if RBBB is really a primarilymanifestation orif it is secondary to myocardial damage extending to conduc-tion system Also the role of RBBB in physiopathology of CDis not well understood One previous study showed that ina cohort of asymptomatic patients with RBBB patients withCD have a worse prognostic regarding cardiac sudden deathwhen compared to other patients with RBBB and no CD[58] Although the influence of having CDwas not comparedwith other classic prognostic factors these data suggest theneed for further studies looking specifically to the prognosisof patients with RBBB secondary to CD Indeed it is welldocumented that having a normal ECG is a marker of goodprognosis in CD but the prognostic meaning of an isolatedRBBB due to CD is unclear [59]


(a) (b)

Diastole Systole

(c)

t1

t2

(d)

Figure 4 Echocardiographic conventional parameters of right ventricle (RV) evaluation (a) Tricuspid Annular Peak Systolic Excursion(TAPSE) from M-mode (b) Systolic wave velocity (1198781015840) of the lateral portion of tricuspid annulus (c) area measurements in diastole andsystole from bidimensional images to calculate fractional area change (FAC) (d) time measurements from tissue Doppler curves in tricuspidannulus to calculate myocardial performance index (MPI) [13] Adapted with permission from Elsevier license number 4143761084119

The real contribution of this electrical disturbance to RVdysfunction has not been investigatedThis contrasts with theconspicuous evidence that left bundle branch block (LBBB)is associated with left ventricle dysfunction [60] Althoughin other disease scenarios RBBB is usually an expressionof RV pressure and volume overload in CD this electricaldisturbance could be a primary reflection of myocardialdamageThe understanding about the role of RBBB in induc-ing delayed RV contraction in RV calculations of functionby cardiac diagnosing methods is frequently ignored Thiseffect was tested using CMR by Marterer et al concludingthat ignoring the RV physiology in RBBB patients leads toa statistically significant underscoring of RV performanceparameters [61]Thus the impact of RBBB inCDas a primarymechanism to RV mechanical dyssynchrony and dysfunc-tion warrants further investigation with dedicated study de-sign

5 Current Imaging Evaluation of theRight Ventricle in CD Focus onNoninvasive Cardiac Diagnostic Tools

51 Echocardiography Evaluation of right ventricle anatomyand function with echocardiography is always challeng-ing Right ventricle unique macroscopic morphology whichincludes an inflow and outflow regions and the main cavitycannot be represented by a simple mathematical geometricmodel Because of this geometric extrapolations to estimate

chamber volumes so useful for bidimensional echocardio-graphic assessment of the LV cannot be applied in thecase of the RV [62] Although understanding right ventricleinvolvement in several disease processes has gained a recentinterest it is still not yet adequately addressed in cardiology[63] Tridimensional echocardiography while promisingstill has some difficulties when imaging the right ventricleas the need to improve the technical spatial resolution toassess the right ventricle free wall [64] Other uniquecharacteristics of right ventricle are additional barriers asthe thin myocardium walls its prominent trabeculationand its contraction mechanics characterized by a predom-inant long-axis (apex-to-basal) shortening of myocardiumfibers

Recognizing these problems a guide on how to measureright ventricle geometry and functionwith echocardiographywas released in 2010 and was further updated and includedin an echocardiography chamber quantification recommen-dation in 2015 [65 66] The document comprises bidimen-sional linear measures of RV cavity at different levels andprojections and functional nonvolumetric parameters such aslongitudinal excursion of tricuspid annulus (TAPSE) tissueDoppler velocity of systolic wave at the lateral portion oftricuspid annulus (S1015840 wave) fractional area change (FAC)during systole myocardium performance index (MPI) alsorecognized as Tei index [67] and the estimate of 119889119875119889119879 fromsystolic time of the tricuspid regurgitation Doppler spectrum[65] (Figure 4)


(a)

(b)

Figure 5 Myocardial deformation analysis of right ventricle (RV) from speckle tracking echocardiography Strain analysis of RV fromrepresentative CC patients demonstrating preserved systolic function in Panel (a) (GLS minus178 FAC 557) and reduced systolic function inPanel (b) (GLS minus84 FAC 105) Both patients have preserved left ventricle ejection fraction Graphics in each panel represent myocardialstrain in (superior right yellow trace) and RV area change in cm2 (inferior right red trace) RV right ventricle EndoGLS EndocardialGlobal Longitudinal Strain FAC Fractional Area Change es end-systolic time

Considering the overall neglectful cardiology approach tothe right ventricle it is understandable why the same gapsof knowledge also exist for CD studies Acquatella in anoutstanding publication survey in 2007 extensively reviewedecho contributions to the field of CDwithout fully addressingthe mixed results of studies of echocardiographic evaluationof RV in CD [68] Despite this neglect from most echocar-diographic studies primarily focusing on the LV assessmentit is possible to conclude that 2D echocardiography can detectright ventricular systolic dysfunction in a high proportionof patients who already have decreased global LV systolicimpairment even at earlier stages of the cardiomyopathy[13 48] Other publications also addressed the potentialof echocardiographic conventional parameters such as 1198781015840TAPSE and MPI to detect right ventricular dysfunction inmore advanced stages of disease and symptomatic patients[69] Some publications also endorsed the ability of echocar-diographic parameters to detect right ventricle dysfunctioneven in patients with the indeterminate form of the disease

using tissue Doppler techniques [49 70] However usingmyocardium performance index (MPI) investigators werenot able to differentiate patients with the indeterminate formof CD from controls [49] Also using 2D speckle trackingBarbosa et al in a study of biventricular function publishednegative results of strain evaluation to differentiate patientswith indeterminate form of CD from controls [50]

Speckle tracking is a relatively new echocardiography tooland discussion about its methodology advantage over otherapproaches is still a topic of interest [71] With this tech-nique the myocardium systolic function can be measuredalong the entire myocardium as deformation (Figure 5) Themyocardium deformation analysis is relatively independentfrom overload conditions [72 73] and because of thisin theory it can be applied to detect myocardial damageeven when compensatory physiological adjustments are stillpreserving the ejection fraction within normal limits [72]Normality values of RV strain by 2D speckle tracking analysiswere recently published [74]


Most of published data using speckle tracking in CDwere focused on left ventricle analysis assessment [50 75ndash77] These investigations used specific vendor software forthe analysis and their methodological approach mainlyabout timing of measured peak (if global or systolic) end-systole definitions and also if endocardial or mesocardiallayer were neither technically uniform [50 75] nor evenwere they completely reported in some of them A definitestandardization [71] in speckle tracking measurements isnecessary to evolve the applicability of this method not onlyin the evaluation of LV deformation but also for the RVassessment Results of a recent published study followinga standardization methodology of measurements of speckletracking concluded that right ventricular free wall strainmeasurement seems to be a method of choice [13] since thesensitivity of the conventional echocardiographic parametersto detect right ventricular dysfunction in CD is intrinsicallyvery low

In summary echocardiography can be used to detect RVdysfunction in CD but with some inherent methodologicallimitations Speckle tracking is a promising tool to assess RVdysfunction in this disease overcoming the lack of sensitivityof conventional 2D and Doppler measurements of func-tion

52 CardiacMagnetic Resonance With its inherent capabilityfor the direct measurement of chamber volumes and thecalculation of biventricular ejection fraction without geo-metric extrapolations CMR is clearly a more advantageousmethod than echocardiography for that purpose In thisregard the method is already considered a gold standard ofventricle volumes quantification [78] This has been assumedin general despite the fact that it has not been studied incomparison with the estimation of ejection fraction basedon ECG-gated radionuclide angiography In the absence ofdirect comparative studies of both methods it may wellbe that the nuclear method which also has no need forany geometric extrapolation (scintigraphy counts are directlyproportional to volumes throughout the cardiac cycle) andhas the advantage of allowing a precise averaging of hundredsof cardiac cycles may stand the test of a comparison withCMR In addition the method of measuring EF with CMRhas not been fully standardized and there are still chal-lenges on its way to more widespread clinical application Inparticular right ventricle ejection fraction normal referencevalues are still not consolidated Despite these caveats itis relevant to emphasize that in CD patients CMR can beused not only to calculate ventricular volumes and ejectionfraction (Figure 6) but also to characterize myocardial tissuealterations (Figure 7)

The utility of CMR in CD was first demonstrated for thestudy of left ventricle systolic function and the detection ofleft ventricle myocardial fibrous tissue and its significance[79ndash82] As mentioned above a recent study by Moreira etal using CMR evaluated the prevalence of RV systolic dys-function in a sizable population of patients with chronic CDIn that study a reduction of right ventricular ejection fractionwas detected in 37of the patients studied usually associated

with left ventricle dysfunction Corroborating the findingsfrom previous studies with other methods Moreira et alshowed the presence of right ventricular systolic dysfunctionin a small subset of these T cruzi chronically infectedsubjects with preserved left ventricular ejection fraction[51]

Therefore even considering the intrinsic difficulties inusing CMR in clinical settings most of them related to costand availability especially curtailed by scarce resources inendemic regions of CD there is now a definite drive for theclinical approach with CMR to evaluate early biventriculardamage in CD

53 Future Perspectives

531 Echocardiography Recent research using a mammalianexperimental model of T cruzi infection that closely mimicshuman chronic Chagas with the advantage of a relativelyshort 8ndash10 months of evolution to chronic phase has allowedthe integration of echocardiography analyses with anato-mopathologic findings [83 84] Somewhat unexpectedly itwas first shown that left ventricle segmental motion abnor-malities are more related to the underlying inflammationprocess than to myocardium fibrosis [85] This is an emerg-ing area of research with a great potential for ldquobench tobedrdquo approach Future correlation between anatomopatho-logic studies and clinical studies can advance knowledge ofthe disease pathophysiology and of therapeutic unfoldingTranslational science thinking can guide clinical researchto design studies testing a more detailed segmental systolicquantification not only in the left but also in the rightventricle to detect early myocardium involvement Regionalspeckle tracking quantification can be a useful tool despite itsreproducibility still being a controversy theme

532 Cardiac Magnetic Resonance Based on the conceptsdescribed along this review of CC being an immune-inflammatory disease affecting both the left and the rightventricles CMR has the potential to detect not only fibrosisbut also myocardium edema and inflammation in orderto further extend seeking for detection of early myocardialdamage CMR techniques as T2 sequences are recentlyemerging in diverse scenarios of myocardial diseases includ-ing infarction and acute myocarditis [86] and the utility ofthe method in CD is an open field for new exploits [80]The potential role of the method in allowing a more accurateassessment of the right ventricular function has already beendocumented in various clinical settings [87]

6 Conclusion

Right ventricle role in cardiovascular physiology and pathol-ogy has been historically neglected Cardiology science is stillldquoon the wayrdquo to understand the right ventricle role into car-diovascular physiology and to detect structural and functionabnormalities in this geometrically complex chamber

Different from other dilated cardiomyopathies CD hasa unique characteristic of frequently early and progressive


(a) (b)

1 2 3

4 5 6

7 8 9

(c)

Figure 6 Volumetric assessment of the RV using CMR Image acquired from cine-resonance using pulse sequences SSFP (Steady-StateFree Precession) showing the tomographic slicing of RV long-axis and limiting adjustments to transversal views from base to apex ((a) and(b)) Yellow lines shows delineation of endocardial borders of RV (c) to further calculation of volumes Adapted from Moreira HT (2015)ldquoAnalise ecocardiografica do ventrıculo direito na doenca de Chagas estudo comparativo com a ressonancia magnetica cardıacardquo (DoctoralDissertation) University of Sao Paulo Ribeirao Preto Brazil Circ Cardiovasc Imaging 2017 10e005571 Adapted with permission fromWolters Kluwer license number 4143770060198

damage involving cell death inflammation and fibrosis notonly in the left but also in the right ventricle myocardiumEvolution of cardiac imaging modalities added currentanalyses of myocardial deformation by speckle trackingechocardiography and both chamber volumetric evaluationand tissue characterization using cardiacmagnetic resonanceThese novel technologies offer new perspective to study rightventricular involvement and to understand the associatedaspects of CD progression in terms of malignant arrhythmias

and heart failure Sudden death the most frequent modeof death in patients with CC occurring even when there ispreserved global LV systolic function should be especiallyamenable to investigations using CMR

Additional Points

Methods for Search Strategy and Selections Data for thisreview were identified by searching Medline PubMed and


Figure 7 Four-chamber slice using CMR with LGE (late gadolin-ium enhancement) sequence in a patient with Chagas cardiomyopa-thy Distinct extensive areas of fibrosis (white signal) (yellow arrows)are seen in the right ventricle free wall Right ventricle dimensionsare still within normal limits Discrete isolated areas of fibrosis arealso noted in the left ventricle

Lilacs Databases and publications in English Spanish or Por-tuguese language were accepted No other kind of selectionof manuscripts to be cited was applied considering most ofavailable published data

Conflicts of Interest

The authors declare that there are no conflicts of interestregarding the publication of this paper

References

[1] K TWeber J S Janicki S Shroff and A P Fishman ldquoContrac-tile mechanics and interaction of the right and left ventriclesrdquoThe American Journal of Cardiology vol 47 no 3 pp 686ndash6951981

[2] J S Janicki and K T Weber ldquoFactors influencing the diastolicpressure-volume relation of the cardiac ventriclesrdquo FederationProceedings vol 39 no 2 pp 133ndash140 1980

[3] I Starr W A Jeffers and R H Meade Jr ldquoThe absence of con-spicuous increments of venous pressure after severe damage tothe right ventricle of the dog with a discussion of the relationbetween clinical congestive failure and heart diseaserdquoAmericanHeart Journal vol 26 no 3 pp 291ndash301 1943

[4] H Brooks R Holland and J Al-Sadir ldquoRight ventricularperformance during ischemia an anatomic and hemodynamicanalysisrdquoTheAmerican journal of physiology vol 233 no 4 ppH505ndashH513 1977

[5] L J DellrsquoItalia ldquoAnatomy andPhysiology of theRightVentriclerdquoCardiology Clinics vol 30 no 2 pp 167ndash187 2012

[6] C Basso D Corrado F I Marcus A Nava and G ThieneldquoArrhythmogenic right ventricular cardiomyopathyrdquo The Lan-cet vol 373 no 9671 pp 1289ndash1300 2009

[7] A Rassi Jr A Rassi and J A Marin-Neto ldquoChagas diseaserdquoThe Lancet vol 375 no 9723 pp 1388ndash1402 2010

[8] A Z Prata A and A Guimaraes ldquoChagas Heart Diseaserdquo inProceedings of the Cardiovascular diseases in the tropics H M ea Shaper A Ed pp 264ndash281 London UK 1974

[9] J A Marin-Neto P Marzullo A C Sousa et al ldquoRadionuclideangiographic evidence for early predominant right ventricular

involvement in patientswithChagasrsquo diseaserdquoCanadian Journalof Cardiology vol 4 no 5 pp 231ndash236 1988

[10] Moreira H T G J Volpe H S Trad et al ldquoRight ventriculardysfunction in Chagasrsquocardiomyopathy Primary involvementor a resonant manifestation of left ventricular dysfunctionrdquoJournal of Cardiovascular Magnetic Resonance vol 16 Supple-ment 1 p 1 2014

[11] C M Prado M R N Celes L M Malvestio et al ldquoEarly dys-trophin disruption in the pathogenesis of experimental chronicChagas cardiomyopathyrdquo Microbes and Infection vol 14 no 1pp 59ndash68 2012

[12] M A Rossi ldquoThe pattern ofmyocardial fibrosis in chronic Cha-gasrsquo heart diseaserdquo International Journal of Cardiology vol 30no 3 pp 335ndash340 1991

[13] H TMoreira G J Volpe J AMarin-Neto et al ldquoRight ventric-ular systolic dysfunction in chagas disease defined by speckle-tracking echocardiography a comparative study with cardiacmagnetic resonance imagingrdquo Journal of the American Societyof Echocardiography vol 30 no 5 pp 493ndash502 2017

[14] WHO Expert Committee on the Control of Chagas DiseaseldquoControl of Chagasrsquo disease second report of the WHO expertcommittee [meeting held in Buenos Aires from 16 to 20 Octo-ber 1989]rdquo WHO Tecnical Report Series 905 WHO LibraryCataloguing-In-Publication Data Brasilia Brasi 1991

[15] C Global Burden of Disease Study ldquoGlobal regional andnational incidence prevalence and years lived with disabilityfor 301 acute and chronic diseases and injuries in 188 countries1990-2013 a systematic analysis for the Global Burden ofDisease Study 2013rdquoThe Lancet vol 386 no 9995 pp 743ndash8002015

[16] C Bern S Kjos M J Yabsley and S P Montgomery ldquoTry-panosoma cruzi and Chagasrsquo disease in the united statesrdquoClinical Microbiology Reviews vol 24 no 4 pp 655ndash681 2011

[17] M I Traina S Hernandez D R Sanchez et al ldquoPrevalence ofChagas Disease in a US Population of Latin American Immi-grants with Conduction Abnormalities on ElectrocardiogramrdquoPLOS Neglected Tropical Diseases vol 11 no 1 article e00052442017

[18] K M Bonney and D M Engman ldquoChagas heart diseasepathogenesis One mechanism or manyrdquo Current MolecularMedicine vol 8 no 6 pp 510ndash518 2008

[19] Z A Andrade S G Andrade G B Oliveria and D R AlonsoldquoHistopathology of the conducting tissue of the heart in ChagasrsquomyocarditisrdquoAmericanHeart Journal vol 95 no 3 pp 316ndash3241978

[20] D S Amorin J A Mello de Oliveira J S Meira de Oliveiraet al ldquoHeart block in Chagasrsquo diseaserdquo Arquivos Brasileiros deCardiologia vol 28 no 1 pp 79ndash82 1976

[21] J A Marin-Neto G Bromberg-Marin A Pazin-Filho M VSimoes and B C Maciel ldquoCardiac autonomic impairment andearly myocardial damage involving the right ventricle are inde-pendent phenomena in Chagasrsquo diseaserdquo International Journalof Cardiology vol 65 no 3 pp 261ndash269 1998

[22] F Koberle ldquoChagasrsquo Disease and Chagasrsquo Syndromes ThePathology of American Trypanosomiasisrdquo Advances in Para-sitology vol 6 no C pp 63ndash116 1968

[23] J A Marin-Neto E Cunha-Neto B C Maciel and M VSimoes ldquoPathogenesis of chronic Chagas heart diseaserdquo Circu-lation vol 115 no 9 pp 1109ndash1123 2007

[24] M A Rossi H B Tanowitz L M Malvestio et al ldquoCoro-nary microvascular disease in chronic chagas cardiomyopa-thy including an overview on history pathology and other


proposed pathogenic mechanismsrdquo PLoS Neglected TropicalDiseases vol 4 no 8 article e674 2010

[25] M V Simoes A O Pintya G Bromberg-Marin et al ldquoRelationof regional sympathetic denervation and myocardial perfusiondisturbance to wall motion impairment in Chagasrsquo cardiomy-opathyrdquo American Journal of Cardiology vol 86 no 9 pp 975ndash981 2000

[26] S A Morris H B Tanowitz M Wittner and J P BilezikianldquoPathophysiological insights into the cardiomyopathy of Cha-gasrsquo diseaserdquo Circulation vol 82 no 6 pp 1900ndash1909 1990

[27] D V Andrade K J Gollob and W O Dutra ldquoAcute ChagasDisease New Global Challenges for an Old Neglected DiseaserdquoPLoSNeglected Tropical Diseases vol 8 no 7 article e3010 2014

[28] A A Nobrega M H Garcia E Tatto et al ldquoOral transmissionof chagas disease by consumption of Acaı palm fruit BrazilrdquoEmerging Infectious Diseases vol 15 no 4 pp 653ndash655 2009

[29] M Z Tavora N Mehta R M Silva F A Gondim V M Haraand A A de Paola ldquoCharacteristics and identification of sitesof chagasic ventricular tachycardia by endocardial mappingrdquoArquivos Brasileiros de Cardiologia vol 72 no 4 pp 451ndash4741999

[30] S G Andrade and M Sadigursky ldquoThe conduction systemof the heart in mice chronically infected with Trypanosomacruzi histopathological lesions and electrocardiographic corre-lationsrdquoMemorias do Instituto Oswaldo Cruz vol 82 no 1 pp59ndash66 1987

[31] F Koberle ldquoThe chronic Chagas cardiopathyrdquo Virchows ArchivFur Pathologische Anatomie Und Physiologie Und Fur KlinischeMedizin vol 330 no 3 pp 267ndash295 1957

[32] A Rassi Jr A Rassi and J Marcondes de Rezende ldquoAmericantrypanosomiasis (Chagas disease)rdquo Infectious Disease Clinics ofNorth America vol 26 no 2 pp 275ndash291 2012

[33] J P Andrade J AMarin-Neto A A Paola et al ldquoI Latin Amer-ican guidelines for the diagnosis and treatment of ChagascardiomyopathyrdquoArquivos Brasileiros de Cardiologia vol 97 no2 supplement 3 pp 1ndash48 2011

[34] J A Marin-Neto and Z A Andrade ldquoWhy is there predom-inance of right heart failure in Chagasrsquo diseaserdquo ArquivosBrasileiros de Cardiologia vol 57 no 3 pp 181ndash183 1991

[35] A C Barreto L Higuchi Mde P L Da Luz et al ldquoComparisonof histologic changes in Chagasrsquocardiomyopathy and dilatedcardiomyopathyrdquo Arquivos Brasileiros de Cardiologia vol 52no 2 1989

[36] C Mady A C Barretto N Stolf et al ldquoEndomyocardial biopsyin the indeterminate form of Chagasrsquo diseaserdquo Arquivos Brasil-eiros de Cardiologia vol 36 no 6 pp 387ndash390 1981

[37] J M Hagar and S H Rahimtoola ldquoChagasrsquo heart diseaserdquoCurrent Problems in Cardiology vol 20 no 12 pp 825ndash9241995

[38] Higuchi M d L E A Lopes A C Barretto et al ldquoEndomy-ocardial biopsy of the right ventricle Significance of the ultra-structural changes in Chagasrsquo cardiopathyrdquo Arquivos Brasileirosde Cardiologia vol 44 no 3 pp 171ndash175 1985

[39] A C P Barretto C Mady E Arteage-Fernandez et al ldquoRightventricular endomyocardial biopsy in chronic Chagasrsquo diseaserdquoAmerican Heart Journal vol 111 no 2 pp 307ndash312 1986

[40] F-X Lescure G Le Loup H Freilij et al ldquoChagas diseaseChanges in knowledge and managementrdquoThe Lancet InfectiousDiseases vol 10 no 8 pp 556ndash570 2010

[41] H F G Freitas P R Chizzola A T Paes A C P Lima andA J Mansur ldquoRisk stratification in a Brazilian hospital-based

cohort of 1220 outpatients with heart failure Role of Chagasrsquoheart diseaserdquo International Journal of Cardiology vol 102 no2 pp 239ndash247 2005

[42] M D C P Nunes M O C Rocha A L P Ribeiro et al ldquoRightventricular dysfunction is an independent predictor of survivalin patients with dilated chronic Chagasrsquo cardiomyopathyrdquoInternational Journal of Cardiology vol 127 no 3 pp 372ndash3792008

[43] M V Simoes A Nonino B P Simoes O C Almeida-FilhoB C Maciel and J A Marin-Neto ldquoReagudization of Chagasmyocarditis inducing exclusive right ventricular failurerdquo Arqui-vos Brasileiros de Cardiologia vol 62 no 6 pp 435ndash437 1994

[44] MV Simoes F A Soares and JMarin-Neto ldquoSeveremyocardi-tis and esophagitis during reversible long standing Chagasrsquodisease recrudescence in immunocompromised hostrdquo Interna-tional Journal of Cardiology vol 49 no 3 pp 271ndash273 1995

[45] F F Souza O Castro-e-Silva J A Marin Neto et al ldquoAcuteChagasic Myocardiopathy After Orthotopic Liver Transplanta-tion With Donor and Recipient Serologically Negative for Try-panosoma cruzi A Case Reportrdquo Transplantation Proceedingsvol 40 no 3 pp 875ndash878 2008

[46] H A Carrasco M Medina G Inglessis A Fuenmayor CMolina and D Davila ldquoRight ventricular function in Chagasdiseaserdquo International Journal of Cardiology vol 2 no 3-4 pp325ndash335 1983

[47] C Mady A V de Moraes N Galiano and L V DecourtldquoHemodynamic study of the indeterminate form of Chagasrsquodiseaserdquo Arquivos Brasileiros de Cardiologia vol 38 no 4 pp271ndash275 1982

[48] M D C P Nunes M D M Barbosa V A A Brum andM O D C Rocha ldquoMorphofunctional characteristics of theright ventricle inChagasrsquo dilated cardiomyopathyrdquo InternationalJournal of Cardiology vol 94 no 1 pp 79ndash85 2004

[49] R G Furtado D Do Carmo Rassi Frota J B M Silvaet al ldquoRight ventricular doppler echocardiographic study ofindeterminate form of chagas diseaserdquo Arquivos Brasileiros deCardiologia vol 104 no 3 pp 209ndash217 2015

[50] M M Barbosa M O C Rocha D F Vidigal et al ldquoEarlydetection of left ventricular contractility abnormalities bytwo-dimensional speckle tracking strain in Chagasrsquo diseaserdquoEchocardiography vol 31 no 5 pp 623ndash630 2014

[51] H T Moreira G J Volpe J A Marin-Neto et al ldquoEvaluationof Right Ventricular Systolic Function in Chagas Disease UsingCardiac Magnetic Resonance Imagingrdquo Circulation Cardiovas-cular Imaging vol 10 no 3 2017

[52] A Rassi Jr A Rassi W C Little et al ldquoDevelopment andvalidation of a risk score for predicting death in Chagasrsquo heartdiseaserdquo New England Journal of Medicine vol 355 no 8 pp799ndash808 2006

[53] A Rassi Jr and A Rassi ldquoPredicting prognosis in patientswith Chagas disease why are the results of various studies sodifferentrdquo International Journal of Cardiology vol 145 no 1 pp64-65 2010

[54] M Pavlicek A Wahl T Rutz et al ldquoRight ventricular systolicfunction assessment Rank of echocardiographic methods vscardiac magnetic resonance imagingrdquo European Journal ofEchocardiography vol 12 no 11 pp 871ndash880 2011

[55] A Pazin-Filho M M D Romano R Gomes Furtado et alldquoLeftVentricular Global Performance andDiastolic Function inIndeterminate and Cardiac Forms of Chagasrsquo Diseaserdquo Journalof the American Society of Echocardiography vol 20 no 12 pp1338ndash1343 2007


[56] R Cardoso D Garcia G Fernandes et al ldquoThe Prevalence ofAtrial Fibrillation and Conduction Abnormalities in ChagasrsquoDisease A Meta-Analysisrdquo Journal of Cardiovascular Electro-physiology vol 27 no 2 pp 161ndash169 2016

[57] S Williams-Blangero T Magalhaes E Rainwater J BlangeroR Correa-Oliveira and J L VandeBerg ldquoElectrocardiographiccharacteristics in a population with high rates of seropositivityfor Trypanosoma cruzi infectionrdquo American Journal of TropicalMedicine and Hygiene vol 77 no 3 pp 495ndash499 2007

[58] J Pimenta N Valente and M Miranda ldquoLong-term follow upof asymptomatic chagasic individualswith intraventricular con-duction disturbances correlating with non-chagasic patientsrdquoRevista da Sociedade Brasileira deMedicina Tropical vol 32 no6 pp 621ndash631 1999

[59] J H Maguire R Hoff I Sherlock et al ldquoCardiac morbidityandmortality due toChagasrsquo disease Prospective electrocardio-graphic study of a Brazilian communityrdquoCirculation vol 75 no6 pp 1140ndash1145 1987

[60] K Vernooy X A AM Verbeek M Peschar and FW PrinzenldquoRelation between Abnormal Ventricular Impulse Conductionand Heart Failurerdquo Journal of Interventional Cardiology vol 16no 6 pp 557ndash562 2003

[61] R Marterer Z Hongchun S Tschauner M Koestenbergerand E Sorantin ldquoCardiac MRI assessment of right ventricularfunction impact of right bundle branch block on the evaluationof cardiac performance parametersrdquo European Radiology vol25 no 12 pp 3528ndash3535 2015

[62] F Sheehan and A Redington ldquoThe right ventricle Anatomyphysiology and clinical imagingrdquoHeart vol 94 no 11 pp 1510ndash1515 2008

[63] F Haddad S A Hunt D N Rosenthal and D J MurphyldquoRight ventricular function in cardiovascular disease part Ianatomy physiology aging and functional assessment of theright ventriclerdquo Circulation vol 117 no 11 pp 1436ndash1448 2008

[64] R M Lang L P Badano W Tsang et al ldquoEAEASE rec-ommendations for image acquisition and display using three-dimensional echocardiographyrdquo European Heart Journal Car-diovascular Imaging vol 13 no 1 pp 1ndash46 2012

[65] L G Rudski W W Lai J Afilalo et al ldquoGuidelines for theechocardiographic assessment of the right heart in adultsa report from the American Society of Echocardiographyendorsed by the European Association of Echocardiographya registered branch of the European Society of Cardiologyand the Canadian Society of Echocardiographyrdquo Journal of theAmerican Society of Echocardiography vol 23 no 7 pp 685ndash713786ndash788 2010

[66] R M Lang L P Badano V Mor-Avi et al ldquoRecommendationsfor cardiac chamber quantification by echocardiography inadults an update from the American Society of Echocardiogra-phy and the European Association of Cardiovascular ImagingrdquoEuropean Heart JournalmdashCardiovascular Imaging vol 16 no 3pp 233ndash271 2015

[67] C Tei L H Ling D O Hodge et al ldquoNew index of combinedsystolic and diastolic myocardial performance a simple andreproducible measure of cardiac functionmdasha study in normalsand dilated cardiomyopathyrdquo Journal of Cardiology vol 26 no6 pp 357ndash366 1995

[68] H Acquatella ldquoEchocardiography in Chagas heart diseaserdquoCirculation vol 115 no 9 pp 1124ndash1131 2007

[69] CA SNascimento VAMGomes S K Silva et al ldquoLeft atrialand left ventricular diastolic function in chronic chagas diseaserdquo

Journal of the American Society of Echocardiography vol 26 no12 pp 1424ndash1433 2013

[70] M V L Barros F S Machado A L P Ribeiro and M O DaCosta Rocha ldquoDetection of early right ventricular dysfunctionin Chagasrsquo disease using Doppler tissue imagingrdquo Journal of theAmerican Society of Echocardiography vol 15 no 10 part 2 pp1197ndash1201 2002

[71] J-U Voigt G Pedrizzetti P Lysyansky et al ldquoDefinitions for acommon standard for 2D speckle tracking echocardiographyConsensus document of the EACVIASEindustry task forceto standardize deformation imagingrdquo Journal of the AmericanSociety of Echocardiography vol 28 no 2 pp 183ndash193 2015

[72] H Blessberger and T Binder ldquoTwo dimensional speckle track-ing echocardiography Clinical applicationsrdquoHeart vol 96 no24 pp 2032ndash2040 2010

[73] H Blessberger and T Binder ldquoTwo dimensional speckle track-ing echocardiography Basic principlesrdquoHeart vol 96 no 9 pp716ndash722 2010

[74] D Muraru S Onciul D Peluso et al ldquoSex- and method-specific reference values for right ventricular strain by 2-dimensional speckle-tracking echocardiographyrdquo CirculationCardiovascular Imaging vol 9 no 2 article e003866 2016

[75] V A M Gomes G F Alves M Hadlich et al ldquoAnalysis ofRegional LeftVentricular Strain in Patients withChagasDiseaseand Normal Left Ventricular Systolic Functionrdquo Journal of theAmerican Society of Echocardiography vol 29 no 7 pp 679ndash688 2016

[76] A Garcıa-Alvarez M Sitges A Regueiro et al ldquoMyocardialdeformation analysis in chagas heart disease with the use ofspeckle tracking echocardiographyrdquo Journal of Cardiac Failurevol 17 no 12 pp 1028ndash1034 2011

[77] M S M Lima H R Villarraga M C D Abduch et alldquoComprehensive left ventricular mechanics analysis by speckletracking echocardiography in Chagas diseaserdquo CardiovascularUltrasound vol 14 no 1 p 20 2016

[78] W G Hundley D A Bluemke J P Finn et al ldquoACCFACRAHANASCISCMR 2010 expert consensus document on car-diovascular magnetic resonance a report of the American Col-lege of Cardiology Foundation Task Force on Expert ConsensusDocumentsrdquo Journal of the American College of Cardiology vol55 no 23 pp 2614ndash2662 2010

[79] C E Rochitte P F Oliveira J M Andrade et al ldquoMyocar-dial delayed enhancement by magnetic resonance imaging inpatients with Chagasrsquo disease A marker of disease severityrdquoJournal of the American College of Cardiology vol 46 no 8 pp1553ndash1558 2005

[80] J A Torreao B M Ianni C Mady et al ldquoMyocardial tissuecharacterization in Chagasrsquo heart disease by cardiovascularmagnetic resonancerdquo Journal of Cardiovascular Magnetic Res-onance vol 17 no 1 p 97 2015

[81] R Kalil E A Bocchi B M Ferreira et al ldquoMagnetic res-onance imaging in chronic Chagas cardiopathy Correlationwith endomyocardial biopsy findingsrdquo Arquivos brasileiros decardiologia vol 65 no 5 pp 413ndash416 1995

[82] R P de Mello G Szarf P R Schvartzman et al ldquoDelayedenhancement cardiac magnetic resonance imaging can identifythe risk for ventricular tachycardia in chronic Chagasrsquo heartdiseaserdquo Arquivos Brasileiros de Cardiologia vol 98 no 5 pp421ndash430 2012

[83] A M B Bilate V M C Salemi F J A Ramires et al ldquoTheSyrian hamster as a model for the dilated cardiomyopathy


of Chagasrsquo disease a quantitative echocardiographical andhistopathological analysisrdquoMicrobes and Infection vol 5 no 12pp 1116ndash1124 2003

[84] L E Ramirez E Lages-Silva JM Soares Jr and E ChapadeiroldquoThe hamster (Mesocricetus auratus) as experimental model inChagasrsquo disease parasitological and histopathological studiesin acute and chronic phases of Trypanosoma cruzi infectionrdquoRevista da Sociedade Brasileira de Medicina Tropical vol 27 no3 pp 163ndash169 1994

[85] L F L De Oliveira M M D Romano E E V De Carvalhoet al ldquoHistopathological correlates of global and segmental leftventricular systolic dysfunction in experimental chronic chagascardiomyopathyrdquo Journal of the American Heart Associationvol 5 no 1 article e002786 2016

[86] Y Amano M Tachi H Tani K Mizuno Y Kobayashi and SKumita ldquoT2-weighted cardiac magnetic resonance imaging ofedema inmyocardial diseasesrdquoThe ScientificWorld Journal vol2012 Article ID 194069 7 pages 2012

[87] A Schmidt B C Maciel and J A Marin-Neto ldquoClinical TrialReport Time is Resonant for Right Ventricular EvaluationrdquoCurrent Cardiovascular Imaging Reports vol 4 no 3 pp 177ndash179 2011

Submit your manuscripts athttpswwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014


MEDIATORSINFLAMMATION

of


Behavioural Neurology

EndocrinologyInternational Journal of



Disease Markers


BioMed Research International

OncologyJournal of



Oxidative Medicine and Cellular Longevity


PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of



Computational and Mathematical Methods in Medicine

OphthalmologyJournal of


Diabetes ResearchJournal of



Research and TreatmentAIDS


Gastroenterology Research and Practice


Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom


in contrast in experimental models of septum dysfunctionbecause of infarction [4]

Based on these physiologic aspects and adding to the factthat many of the studies were designed on a volume-pressurerelation basis it is possible to understand why cardiologyscience neglected theRVas a ldquosecondary chamberrdquo or a ldquopass-ing chamberrdquo [5] Nonetheless knowledge about primarymyocardial conditions affecting the RV without concomitantpressure overload of this chamber as inUhlrsquos anomaly andRVdysplasia reinforces the need of other theories to explain thereal influence of right ventricular function in cardiovascularphysiology The fact that RV dysplasia includes a phase ofright-sided cardiac failure beyond the arrhythmic clinicalcomplications gives an insight to the fact that advanced RVmuscle impairment can be clinically significant and directlyleads to intrinsic heart failure syndrome [6]

There is evidence that CD causes a peculiar right ventricleinvolvement first because evolution of the disease to heartfailure usually includes prominent right heart failure symp-toms in absence of or with only mild pulmonary congestion[7 8] second because there is direct evidence of myocardialdamage of the right ventricle in human myocardial biopsiesand postmortem studies as well as in animal experimentalmodels of T cruzi infection and finally because there is aproportion of patients with early and isolated right ventricledysfunction when evaluated by different cardiac imagemeth-ods [9 10]

However exploring the right ventricle with imagingdiagnostic tools is still a challengeThe accumulated evidenceabout ventricular systolic function inmost diseases is derivedfrom echocardiography Two-dimensional echocardiographyneeds geometrical assumptions to estimate ventricular vol-umes and the right ventricle simply does not have a mathe-matically defined geometrical form

This review explores the right ventricle anatomic andfunctional involvement in Chagas cardiomyopathy (CC)while highlighting the contribution of cardiac imaging diag-nostic methods in the field

2 Chagas Cardiomyopathy (CC)

CD was recognized by WHO as one of the worldrsquos 13 mostneglected tropical diseases with a high prevalence of indi-viduals at risk of infection in South and Central Americaand with the highest rates of mortality between all neglecteddiseases [14] Although its prevalence had slightly declinedthrough the last decade it can reach 114 of heart failurecauses in specific endemic regions of Brazil [15] Althoughoriginally confined to poor rural areas of Latin Americamigration movements contributed to spread CD to nonen-demic countries in Europe Canada and USA [16 17]

CD is caused by the T cruzi protozoan infection thatleads in most cases to a myocardial chronic inflammatoryresponse [7] Myocardial damage is probably a result of im-balance between parasite persistence and adverse immune-inflammatory response [18] which result in a broad spectrumof tissue lesions Myocardium disease is characterized bya low-intensity slowly progressive but incessant myocardi-tis which leads to impairment of contractile function and

dilatation of cardiac chambers [7] Histologically there is awidespread destruction of myocardial cells edema diffusefibrosis mononuclear cell infiltration and scarring of theconduction system and the contractile myocardium [11 19](Figure 1) Early stages of the disease are still not fully under-stood but conduction system abnormalities can occur beforemyocardium contractile function impairment [20] Cardiacautonomic dysfunction may also be an early consequenceof the loss of cardiac neuronal parasympathetic activity [21ndash23] Microvascular coronary dysfunction also occurs and itsmechanism is still not well known but is likely to contributeto contractile function damage [24ndash26] Progression of themyocardium damage results in a scenario of widespreadsubstitution by fibrous tissue which is the core of botharrhythmogenesis and heart failure

CD includes an acute and a chronic phase Acute infectionis usually underdiagnosed There is a recent increase ofcases secondary to reactivation from the chronic phase byblood transfusion or transplantation of solid organs andcongenital or oral contaminations [27 28] Most of acutecases run through an asymptomatic clinical course Whensymptoms occur they include fever malaise enlargement ofliver spleen and lymph nodes and subcutaneous localizededema [7] The grade and type of immunological responsehave a key role in controlling parasitemia during acute phaseand permit most of patients to undergo to the chronicclinically silent indeterminate form of disease Howeversome 30 of infected subjects will present symptoms andor signs of cardiac damage 10ndash30 years later [7] Bradycardiaand conduction system abnormalities can occur early in theevolution of disease as well as frequent ventricular ectopicbeats [17 19] Ventricular tachycardia is ominous and can beresponsible for sudden cardiac death even in less advancedstages of the disease [29] Other typical ECG alterationsinclude right bundle branch block and left anterior fascicularbundle block which can be combined [19 30]

Myocardial damage typically causes regional contractiondisturbances in the left ventricle and the virtually pathog-nomonic apical aneurisms [22 31] Global LV dilatationand systolic dysfunction are also often seen as the diseaseprogresses When heart failure supervenes it is usually withbiventricular manifestations and systemic congestion can bemore impressive when compared to pulmonary congestionPatients with cardiac form of CD are seen frequently incardiac units and clinics all around South and CentralAmerica They usually present with heart failure symptomsduring recurrent hospital admissions In many cases symp-toms and signs of systemic congestion are very prominentThey usually complain of lower limbs edema weight gainincrease in abdominal volume and pain associated withhepatomegaly This conspicuous form of right-sided heartfailure presentation was well described since the first reportson clinical CD [32ndash34] and still puts a challenge to treatmentPatients need high doses of diuretics and vasodilators andsometimes the use of intravenous inotropes although it withno proven benefit onmortality is warranted as a symptomatictreatment resource [33]

Because of these peculiar aspects of CD cardiomyopa-thy diagnostic tools capable of detecting early myocardial


(a) (b) (c)

(d) (e) (f)

p lt 0001p lt 0001

p lt 005

Control 30 100

Days postinfection

0

20

40

60

80

100

120

140

Num

ber o

f mon

onuc

lear

cells

RV

fiel

d

(g)

p lt 0001 p lt 001

p lt 005

Control 30 100

Days postinfection

0

20

40

60

80

100

120

140

Num

ber o

f mon

onuc

lear

cells

LV

fiel

d

(h)







p lt 001

p lt 005

p lt 005

NSNSNS

10

8

6

4

2

0

Col

lage

n LV

fiel

d (

)

Col

lage

n RV

fiel

d (

)

Control 100


4

3

2

1

030 Control 10030

(a)

(b)























(a) (b)

Diastole Systole

(c)

t1

t2

(d)








(a)

(b)















6 Conclusion




(a) (b)

1 2 3

4 5 6

7 8 9

(c)




Additional Points







References





































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















(a) (b) (c)

(d) (e) (f)

p lt 0001p lt 0001

p lt 005

Control 30 100

Days postinfection

0

20

40

60

80

100

120

140

Num

ber o

f mon

onuc

lear

cells

RV

fiel

d

(g)

p lt 0001 p lt 001

p lt 005

Control 30 100

Days postinfection

0

20

40

60

80

100

120

140

Num

ber o

f mon

onuc

lear

cells

LV

fiel

d

(h)







p lt 001

p lt 005

p lt 005

NSNSNS

10

8

6

4

2

0

Col

lage

n LV

fiel

d (

)

Col

lage

n RV

fiel

d (

)

Control 100


4

3

2

1

030 Control 10030

(a)

(b)























(a) (b)

Diastole Systole

(c)

t1

t2

(d)








(a)

(b)















6 Conclusion




(a) (b)

1 2 3

4 5 6

7 8 9

(c)




Additional Points







References





































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















p lt 001

p lt 005

p lt 005

NSNSNS

10

8

6

4

2

0

Col

lage

n LV

fiel

d (

)

Col

lage

n RV

fiel

d (

)

Control 100


4

3

2

1

030 Control 10030

(a)

(b)























(a) (b)

Diastole Systole

(c)

t1

t2

(d)








(a)

(b)















6 Conclusion




(a) (b)

1 2 3

4 5 6

7 8 9

(c)




Additional Points







References





































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





































(a) (b)

Diastole Systole

(c)

t1

t2

(d)








(a)

(b)















6 Conclusion




(a) (b)

1 2 3

4 5 6

7 8 9

(c)




Additional Points







References





































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















(a)

(b)















6 Conclusion




(a) (b)

1 2 3

4 5 6

7 8 9

(c)




Additional Points







References





































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of


























6 Conclusion




(a) (b)

1 2 3

4 5 6

7 8 9

(c)




Additional Points







References





































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















(a) (b)

1 2 3

4 5 6

7 8 9

(c)




Additional Points







References





































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





















References





































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of



























































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of














