MRI features of

Nonischemic dilated cardiomyopathies

and its clinical correlation.

PROJECT REPORT

Submitted during the course of DM Cardiology by

Dr. DIBYA RANJAN BEHERA

DM Trainee

DEPARTMENT OF CARDIOLOGY

Jan 2015 – Dec 2017

SREE CHITRA TIRUNAL INSTITUTE FOR MEDICAL SCIENCES AND TECHNOLOGY

TRIVANDRUM, KERALA

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TITLE

MRI features of

Nonischemic dilated cardiomyopathies

and its clinical correlation.

Principal Investigator:

Dr. Dibya Ranjan Behera

Senior Resident,

Department of Cardiology, SCTIMST

Guide:

Dr. Ajit Kumar V.K.,

Professor and Head

Department of Cardiology, SCTIMST

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DECLARATION

I hereby declare that this thesis titled “MRI features of Nonischemic Dilated

cardiomyopathies and its clinical correlation” has been prepared by me

under the capable supervision and guidance of Dr. Ajit Kumar V. K., Professor

and Head, Department of Cardiology, Sree Chitra Tirunal Institute for Medical

Sciences & Technology, Thiruvananthapuram.

Date: Dr. Dibya Ranjan Behera,

Place: Thiruvananthapuram DM cardiology resident,

Department of Cardiology SCTIMST,

Thiruvananthapuram.

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CERTIFICATE

This is to certify that this thesis titled “MRI features of Nonischemic Dilated

cardiomyopathies and its clinical correlation”, is a bonafide work of Dr. Dibya

Ranjan Behera, DM Cardiology Resident and has been done under my direct

guidance at Sree Chitra Tirunal Institute for Medical Sciences & Technology,

Thiruvananthapuram. He has shown keen interest in preparing this project.

Date: Dr. Ajit Kumar V.K.,

Place: Thiruvananthapuram Professor and Head

Department of Cardiology,

SCTIMST

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CERTIFICATE

This is to certify that this thesis titled “MRI features of Nonischemic

Dilated cardiomyopathies and its clinical correlation”, is a bonafide work

of Dr. Dibya Ranjan Behera, DM Cardiology Resident and has been done

under my direct guidance at Sree Chitra Tirunal Institute for Medical Sciences

& Technology, Thiruvananthapuram. He has shown keen interest in preparing

this project.

Date: Dr. Ajit Kumar V.K.,

Place: Thiruvananthapuram Professor and Head

Department of Cardiology,

SCTIMST

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ACKNOWLEDGEMENT

It is a genuine pleasure to express my deep sense of thanks and

gratitude to my mentor and guide Dr. Ajit Kumar V.K., Professor and

head, Department of Cardiology, SCTIMST for his valuable inputs,

expertise knowledge and continued support to accomplish this project.

I owe a deep sense of gratitude to Dr. T.R. Kapilamoorthy and Dr.

Anees T. for their constant guidance, encouragement and immense support

throughout the project.

I am very grateful to Dr. Jagan Mohan Tharakan for his inspiring

attitude, and amicable nature which helped me in shaping up this thesis.

I take this opportunity to record my sincere thanks to all the faculty

members of Department of Cardiology, SCTIMST for their critical review

of the thesis, besides their help in innumerable ways which has made this

thesis possible.

I am thankful to all my fellow colleagues in the Department of

Cardiology, SCTIMST for their help and guidance.

My sincere thanks to technical, nursing, medical records department

and computer division staff of SCTIMST for their extreme co-operation

and support.

I would like to express my gratitude to my parents Mr. Ramesh

Chandra Behera and Mrs. Suhasini Behera for their encouragement, my

supportive wife Dr. Abhilipsa Acharya, who is always at my side when I

needed her, and my son Kousthuv, who served as my inspiration.

Above all, to the Great Almighty, the author of knowledge and

wisdom, for strength and peace of mind he bestowed upon me.

Dibya Ranjan Behera

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Table of contents

1. Introduction 1

2. Review of literature 2

3. Aim and Objective 18

4. Methods 19

5. Results 24

6. Discussion 55

7. Limitations 64

8. Conclusion 65

9. Bibliography 66

10. Annexure

Abbreviation 75

Proforma 76

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INTRODUCTION

Non-ischemic dilated cardiomyopathy (NIDCM) is the most common form of

cardiomyopathy. Till now transthoracic echocardiography has been the first line of imaging

modality to diagnose cardiomyopathy. But it has its own limitations. Cardiac MRI (CMR)

is increasingly recognized as a noninvasive test of paramount importance in NIDCM. It

not only helps in accurate diagnosis of NIDCM, also helps in differentiating its from

ischemic cardiomyopathy. It has the ability to differentiate and diagnose various forms of

NIDCM. Observational studies so far has shown that the CMR helps in risk stratification

based on presence of late gadolinium enhancement (LGE). Presence of LGE has been

shown as poor prognostic marker in majority of studies with few exception. Thus LGE-

CMR may help in further risk stratification in NIDCM patients beyond conventional risk

markers, which may have further therapeutic implication.

So the current study was contemplated to prove or disprove the above observations.

Surprisingly, there is no data from our country also regarding this.

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REVIEW OF LITERATURE

Cardiomyopathies are chronic progressive myocardial disorders with a distinct

pattern of morphological, functional and electrophysiological changes. The expert

consensus panel (2006) of the American Heart Association proposes the following

definition: “Cardiomyopathies are a heterogeneous group of diseases of the myocardium

associated with mechanical and/or electrical dysfunction that usually (but not invariably)

exhibit inappropriate ventricular hypertrophy or dilatation and are due to a variety of causes

that frequently are genetic. Cardiomyopathies are either confined to the heart or are part of

generalized systemic disorders, often leading to cardiovascular death or progressive heart

failure-related disability.” (1)

Dilated cardiomyopathy (DCM) represents the most common cardiomyopathy. (1)

Dilated cardiomyopathy is characterized by dilatation and impaired contraction of the left

ventricle or both ventricles, in which the degree of myocardial dysfunction is not explained

by the abnormal loading conditions or the extent of ischemic damage. Non ischemic DCM

(NIDCM) is defined as depressed systolic function (left ventricular ejection fraction (LV-

EF) <50%) on a non-CMR study in the absence of significant coronary artery disease

(defined as >50% luminal stenosis on coronary angiography and/or a history of coronary

revascularisation or myocardial infarction), valvular disease, hypertensive heart disease

(1995 WHO/International Society and Federation of Cardiology criteria.) (2)

It’s of mainly 2 types.

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Primary forms - genetic, acquired, or mixed conditions in which the pathological

involvement is predominantly limited to the myocardium and associated with a strong

genetic inheritance in idiopathic cases (≈30%of patients).

In secondary DCM -systemic affections from autoimmune, cytotoxic, infective or

metabolic diseases.

Recognition and differentiation of the underlying pathological substrate leading to

ventricular dilatation may be crucial not only to specifically the target patients therapy

(e.g., treatment of heart failure symptoms versus revascularization versus

immunosuppressive and/or antiviral) but also for better individual risk stratification

because of the extremely variable prognostic implications associated with the different

forms of disease.(3,4)

Routine diagnostic imaging workup of patients with DCM (including

echocardiography, selective coronary angiography, and, when indicated, endomyocardial

biopsy) has been integrated in the last few years with the use of cardiac magnetic resonance

(CMR) which allows identifying and characterizing the presence and location of

myocardial damage in most of the cases combining its unique tissue characterization

capabilities with the assessment of biventricular regional and global function.

Now we will review the role of CMR in the evaluation of DCM, analyzing

respective strengths and limitations in the light of the current literature and technological

developments.

CMR Acquisition Protocol and Features:

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CMR helps in evaluation and quantification of LV dilatation and systolic

dysfunction and detection of possible underlying tissue abnormalities particularly

myocardial fibrosis. (1,5,6)

A standard imaging protocol in DCM includes a four-chamber horizontal long-axis,

two-chamber vertical long-axis, and short-axis views using breath-hold steady-state free

precession (SSFP) cine sequences with full coverage of both ventricles to provide

assessment of biventricular volumes and global and regional functions (Table 1).

Table.1. Different MRI techniques used in NIDCM imaging.

MRI Sequence Information provided CMR imaging features

Cine-SSFP

Regional and global

biventricular function

Ventricular mass and

parietal wall thickness

Dilated left or biventricular cavities

Reduced ejection fraction

Parietal wall thickness normal or slightly

reduced (<5.5 mm)

T2w-STIR

Myocardial free water

content increase

reflecting a specific

inflammatory changes

Suggest active inflammation, eg, active

myocarditis

LGE

Tissue fibrosis/scar (i) No enhancement

(ii) Subendocardial or transmural

enhancement suggest previous

infarction

(iii) Patchy or longitudinal striae of mid-

wall in DCM

T1-mapping

Depiction of diffuse

myocardial fibrosis

Generation of T1 maps for the

quantification of decay in myocardial

signal intensity

Abbreviations: SSFP, Steady state free precession; T2wSTIR, T2 weighted short tau

inversion recovery; LGE, late gadolinium enhancement; DCM, dilated cardiomyopathy.

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CMR is now considered the reference technique for the quantification of ventricular

volumes and functional parameters, to measure wall thickness and ventricular mass in

patients with DCM.(7–9) In advanced cases, LV dysfunction may be associated with

diffuse myocardial wall thinning (diastolic wall thickness < 5.5 mm). (10)

T2-weighted short-tau inversion recovery (T2w-STIR) imaging using an ECG-

gated triple inversion recovery (IR) technique is recommended to depict tissue edema when

an overlapping active inflammatory process is suspected such as in myocarditis, acute

myocardial infarction, Takotsubo syndrome, sarcoidosis.(11)

Gadolinium is biologically inert tracer that freely distributes in extracellular space

but does not cross the intact cell membrane. Due to a combination of increased extracellular

volume and slower washout kinetics, there is a relative accumulation of gadolinium in areas

of necrosis, fibrosis, infiltration, and inflammation in the late washout phase Gadolinium

is a paramagnetic substance which shortens the T1 / T2 decay time and hence cause hyper

enhancement.(12) A standard acquisition protocol includes late enhancement imaging with

T1 weighted inversion recovery images acquired 10–20 minutes after contrast

administration (also called late gadolinium enhancement or LGE), usually obtained using

a segmented 2D or 3D inversion recovery gradient-echo breath-hold approach, with

inversion time optimized to null myocardial signal intensity. Phase-sensitive inversion

recovery (PSIR) reference imaging incorporates the phase polarity information that

enhances myocardial tissue contrast. It is also recommended to ensure matching section

position and same slice thickness between IR-CE and cine- SSFP imaging in order to obtain

direct comparison between regional wall motion abnormalities and LGE findings.(13) Use

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of IR-CE imaging may be helpful to characterize the myocardium and to differentiate DCM

patients from LV dysfunction related to CAD.(14)

LGE has been described as being present in patients with DCM in 12–67% of the

cases.(15) (15–17) The most common pattern being characterized by a mid wall linear

distribution likely representing the intramural layer of septal fibrosis which has been

observed in pathologic samples.(18) Mc Crohon et al. found three different no LGE

patterns in 59% of patients with DCM. Rest 41 % have LGE and two type of patterns of

LGE : (a) subendocardial or transmural enhancement indistinguishable from patients with

previous infarction , and (b) patchy or longitudinal striae of midwall enhancement clearly

different from the distribution in patients with CAD (28%). (14) However, since LGE is

ascribed to relative accumulation of gadolinium in areas of damaged myocardium, LGE-

CMR techniques may miss a diffuse type of fibrosis. (19)

Myocardial T1-mapping techniques have also been recently proposed for the

depiction of diffuse myocardial fibrosis, undetectable with conventional IR-CE CMR

techniques. (20) The basic principle relies on the shortening of T1-relaxation time of

myocardial tissue which directly correlated with the amount of interstitial fibrosis with

collagenous replacement. (21)

Clinical implications of CMR in DCM patients:

Current clinical implication of CMR in DCM patients are

1. evaluation of global biventricular structure and function

2. differential diagnosis in nonischaemic forms

3. differential diagnosis between ischaemic and nonischaemic forms

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4. detection of intracavitary thrombi

5. prognostic stratification

Evaluation of global biventricular structure and function:

Cine images usually show LV hypokinesia and increased volumes in DCM.

Roughly, the end-diastolic volumes that constitute a DCM are more than 140 mL for the

LV and more than 150 ml for the RV; these data may be more accurate if indexed to the

body surface area. In Cine -SSFP, the normal LV end-diastolic volume (EDV)/BSA

(mL/m2) in males is 82.3 ± 14.7 and in females is 77.7 ± 10.8. So values more than this

are considered as dilated LV. (22)

Evaluation of global biventricular systolic function with cine-SSFP is now regarded

as the gold standard imaging technique. It is not affected by the geometric assumptions

used in 2D echocardiography for the left ventricle (such as the area/length method).

Furthermore, the approximation in delineating endocardial border with CMR approach is

considerably less than with 2D echocardiography minimizing operator dependence and

intra- and inter-observer reproducibility variability(23,24).

In DCM, LV ejection fraction is the strongest predictor of progression to heart

failure, while LV volume and mass are independently correlated with mortality and

morbidity; therefore accurate quantification of all these parameters is essential for adequate

patient’s evaluation and also to monitor progression of disease and response to therapy.(25)

Bourantas et al showed that RV dilatation and dysfunction also significantly predicts

adverse outcome in DCM patients. (26)

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Chamber enlargement is also associated with valvular insufficiency which can be

assessed with phase-contrast sequences representing an accurate technique for quantifying

the severity of valve regurgitation and for providing information on diastolic function. (27)

Detection of intracavitary thrombi :

CMR is the preferred diagnostic tool to recognize its presence which is depicted as

a soft-tissue intracavitary lesion, nonenhancing on postcontrast IR-CE images and with a

variable signal intensity on either T1 or T2 images.(28) The technique has shown an

excellent sensitivity and specificity for LV thrombus detection and is superior to both

transthoracic and trans esophageal echocardiography. (29)

Differential diagnosis between ischemic and nonischemic forms :

The diagnosis of NIDCM starts with the exclusion of ischemic cardiomyopathy

(ICM). Generally, coronary angiography is routinely performed for the differentiation.

NIDCM Is diagnosed when patients have no obstructive coronary arteries or coronary risk

factors. But, no obstructive coronary artery on angiography is not synonymous with not

having ICM. (14) The spontaneous recanalization after coronary artery occlusion caused

by a rupture of a minimally stenotic unstable plaque, embolization or any spasm may

mask the cause. Conversely, it is not uncommon that patients with DCM have CAD. Isner

et al through an autopsy study in DCM patients has described occurrence of

subendocardial and transmural fibrosis indistinguishable from ischemic lesions.(30)

CMR is currently recognized as a useful tool to know whether the LV dysfunction

is caused by CAD. Cine-SSFP CMR with its excellent spatial and temporal resolution is

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able to detect regional wall motion abnormalities and wall thinning in a coronary arterial

territory. A subendocardial or transmural LGE in CMR involving a coronary artery

distribution also indicates ischemic cardiomyopathy as the ischemic wave front starts from

subendocardium.

On the other hand, NIDCM mostly show a lack of LGE . The most common

distribution of LGE is mid-wall enhancement, followed by patchy or diffuse striated LGE.

(14) The distribution of LGE is unrelated to any particular coronary arterial territory. This

LGE distribution also shown to correspond to focal fibrosis at autopsy. (31)

The mid wall LGE pattern may also represent the morphological correlate of an

chronic inflammatory process, rather than a focal fibrosis,. De Cobelli et al. found LGE in

70% of patients with chronic heart failure and histologically proven chronic myocarditis.

Mid wall LGE was the most common pattern of LGE distribution found in their series

suggesting that IRCE CMR may noninvasively identify areas of myocardial damage due

to chronic inflammation.(32)

Differential diagnosis of non-ischemic forms :

Differentiation between various forms of non-ischemic DCM is still a complex and

partially investigational issue. The unique tissue characterization ability of CMR offers a

significant additional diagnostic contribution to the conventional diagnostic tools. (33–36)

CMR, in general, allows characterization of acute versus chronic injuries using T2w-

imaging and T2-mapping techniques (T2-STIR). Quantification of intramyocardial iron

deposition can be done with T2∗ techniques in patients with hemochromatosis. LGE –

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CMR provides data regarding necrosis/fibrosis, which is a valuable noninvasive

alternative to endomyocardial biopsy. (37)

A pattern-based approach of LGE is described in literature based on the concept

that the location (subendocardial, transmural, subepicardial, mid myocardial) and pattern

(focal or diffuse) of abnormal LGE allow differentiation between ischemic and

nonischemic cardiomyopathies as well as differential diagnoses in nonischemic forms.(38)

(Figure1. Patterns of hyperenhancement (HE) with MRI in various disease states, with

localization for ischemic versus nonischemic lesions. HTN = hypertension. (39)

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Table.2 CMR features of different non ischemic dilated cardiomyopathies.

Non ischemic

Cardiomyopathy

LGE distribution

LGE

patterns

Other CMR features Intra-

cardic

Intra-

myocardium

Idiopathic Dilated

cardiomyopathy

Inter-

ventricular

septum

Mid-wall Patchy/

diffuse

Diffuse LV wall thinning,

shortened post-

contrast T1

End-stage HCM

Diffuse Any Patchy,

diffuse

LV dilatation with

inhomogenous LV wall

thickening

Cardiac sarcoidosis

Any Sub epicardial,

mid myocardial

Patchy,

difuse

myocardial edema in

T2-STIR

Stress

cardiomyopathy

Regions

with

ballooning

Any Patchy Transient Myocardial

ballooning,

RV motion abnormality

Cardiac amyloidosis

Any Subendocardial,

transmural

Circumferenti

al/ Diffuse

Diffuse hypertrophy, thickened

IAS, valve leaflets,

Biatral enlargement

Myocarditis

Any Subepicardial/

mid myocardial

Diffuse/

patchy

Myocardial edema in

T2-STIR, EGE

LV non-compaction

At

noncompac

ted regions

subendocardial patchy High non-

compacted/compacted

myocardial

ratio

Cardiac

hemochromatosis

NA NA NA Shortened T2-Star

Abbreviations: LV: Left ventricular; LGE: Late gadolinium enhancement; EGE: Early

gadolinium enhancement CMR: Cardiac magnetic resonance; RV: Right ventricular; NA:

Not available information; ICM, Ischemic; NICM: Non-ischemic; DCM: Dilated

cardiomyopathy; HCM: Hypertrophic cardiomyopathy.

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Idiopathic DCM is diagnosed when NIDCM is present but no cause is made out.

CMR showed dilated LV cavity with thinned walls. Most of them are LGE negative. LGE

positivity varies from 12% to 67% as mentioned earlier. Most commonly LGE is present

in mid myocardial region of IVS.

Familial DCM is defined as DCM in two or more first or second degree relatives.

Without proper screening it may be missed in up to 18% of cases. CMR features resemble

that of idiopathic DCM.(40,41)

Myocarditis is usually viral in origin. Although spontaneous recovery is common,

5-10% of cases may progress to chronic dilated cardiomyopathy. Due to patchy

involvement the use of endomyocardial biopsy (EMB) for diagnostic purpose is limited.

T2-STIR CMR shows focal areas of increased signal intensity, representing active

inflammation/edema. Myocardial necrosis on histology is well correlated with both early

and late gadolinium enhancement. (42)Cine-SSFP CMR may show regional wall motion

abnormalities. The LGE is subepicardial, mostly in lateral wall and in a nonischemic

pattern of distribution.

End stage HCM resembles dilated cardiomyopathy. Matoh et al showed that end

stage HCM patients had more LGE extent than the DCM patients, and LGE volume

correlated to lower global and local LV function. (43) LGE-CMR may be useful to evaluate

myocardial damage in HCM patients, and to differentiate the dilated phase of HCM from

DCM. LGE is also a poor prognostic marker in end stage HCM patients. (44)

Cardiac involvement in amyloidosis leads to thickening of ventricular and atrial

walls and the atrio-ventricular valves. CMR shows above findings along with pleural /

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pericardial effusion. The thickness of the interatrial septum more than 6 mm is fairly

specific for amyloidosis.(45) On LGE- CMR , a distinctive pattern of LGE is frequently

seen with circumferential hyperenhancement of the subendocardium or a global transmural

pattern often including the interatrial septum and right ventricle. (46)This LGE pattern has

a high diagnostic accuracy for diagnosing cardiac amyloid compared to EMB and also has

been shown as the single best noninvasive imaging parameter for cardiac amyloid. (47,48)

The presence of LGE also has been shown to be associated with poor prognosis. (49)

Cardiac involvement in sarcoidosis occurs in 20-30% of cases. CMR cine-SSFP

shows localized areas of wall thinning and regional wall motion abnormalities due to

underlying disease activity. T2 –STIR images shows high-signal intensity in areas of

active myocardial inflammation. LGE shows areas of myocardial damage and may help

guide the site for endomyocardial biopsy. LGE-CMR shows various non specific LGE

patterns, including patchy, midwall, subepicardial, or subendocardial, distribution with a

predilection for the basal and mid-septal segments. (50) The presence of LGE portends a

nine-fold higher rate for adverse events (death, VT/ defibrillator shock). (51,52)

Peripartum cardiomyopathy arises in the last month of pregnancy or within 5

months postpartum with 75% of the cases manifesting in the first 2 months after delivery.

Mouquet et al found that CMR shows dilated LV dimensions with decreased LV function

and no LGE. (53) But Arora et al found presence of LGE in 25 to 30% of cases , which

also was associated with poor long term prognosis. (34)

Chemotherapy induced cardiomyopathy is mostly described following

anthracyclin based chemotherapy. (54,55)CMR shows dilated LV dimensions with

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decreased LV function. Role of LGE –CMR in this group of patients is still investigational.

Draft et al , in 53 patients with anthracyclines induced cardiac toxicity showed that changes

in LV end-systolic volumes, LV strain, pulse wave velocity, and LVEF by CMR within 6

months of receiving anthracyclines, but no new LGE. (56)

Prognostic stratification :

As already mentioned above, LGE may also provide intriguing information

regarding patients’ risk stratification. (3)

Several previous studies showed the lack of relationship between the presence of

LGE or LGE volume, and LV volume and function. (43,57) In contrast, Lehrke et al found

that LGE presence is associated with adverse myocardial remodeling and dilated LV

volumes with poor LV function. (25)

In DCM, a series of factors is associated with adverse prognosis, such as age,

gender, LVEF, QRS duration and cardiac biomarkers. (58) Although most of the papers

showed LGE as a poor prognostic marker , still this remains controversial.(59)

The mid-wall LGE in DCM correlates with intraventricular conduction disturbance,

and is independently predictive of sudden cardiac death (SCD) or ventricular tachycardias.

(60) There is a large series of papers in literature reporting that the presence of mid-wall

enhancement is predictive of inducible ventricular tachycardia allowing the stratification

of patient’s risk and the selection of ideal candidate for ICD. LGE-CMR can also help to

identify the arrhythmogenic substrate and plan an appropriate mapping and ablation

strategy. (16,25,61–63)

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Assomull et al. also correlated LGE with mortality and cardiovascular events (HR,

3.4; CI, 1.4 to 8.7) and found that it was the best predictor of sudden cardiac death (HR,

5.4). (16)

The same observation was found by Wu et al. who reported that LGE predicted

adverse outcomes in patients scheduled for ICD implantation with a higher event rate (heart

failure, appropriate ICD discharge, and cardiac death, 44%versus 8%; 𝑃 = 0.001;HR, 8.2;

CI, 2.2 to 30.9; 𝑃 = 0.002). (64)

In contrast, Hombach et al. did not reproduce the same results and found that mid

wall enhancement was not associated with an independent prognostic impact, highlighting

the prominent still investigational nature of those studies requiring further clinical

validation from large prospective dedicated trials. (59) In this regard, a large prospective

longitudinal study of 472 patients with DCM with a median follow-up of 5.3 years was

recently published providing evidence that the assessment of mid-wall fibrosis with LGE-

CMR imaging was independent prognostic information beyond LVEF in patients with

nonischemic dilated cardiomyopathy (HR, 2.43 (95% CI, 1.50–3.92); 𝑃 < 0.001).(3)

One recent metanalysis has shown that LGE in patients with NIDCM is associated

with increased risk of all-cause mortality, heart failure hospitalization, and SCD.. It also

concluded that detection of LGE by CMR has excellent prognostic characteristics and may

help guide risk stratification and management in patients with NICM. (65)

Not only mere presence of LGE but the amount of LGE volume determines the

adverse outcome. Shimuzu et al (63) visually quantify LGE volume in NIDCM patients

and found that the incidence of cardiac events was significantly higher in group with LGE

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extent > 10% of LV volume than the group with <10% ( 36% vs 2 % , Log rank , p =

0.0001). Similarly Poyhonen et al, (66)visually quantified LGE in NIDCM patients and

showed that LGE volume > 17% of LV volume was the strongest predictor of bad

prognosis. Similar results from other studies showed that extensive LGE lead to the

impairment of cardiac function, the propensity to ventricular arrhythmias and high

probabilities of cardiac mortality and morbidity. (25,67). Therefore, the analysis of LGE

volume and not only the presence of LGE, may be valuable to predict prognosis and

identify high-risk patients in DCM.

One recent article by Tateshi et al showed added benefit of systolic blood pressure

response (SBPR) during exercise to LGE positivity in DCM patients. Patients with LGE-

positive and SBPR <40 mm Hg had a significantly high cardiac events (HR 2.08, 95% CI

1.06 to 4.11, p=0.034). But, there was no significant difference in the cardiac event-free

survival rate between the LGE positive + SBPR ≥40 mm Hg and LGE-negative +SBPR

<40 mm Hg groups (p=0.736).

LGE also determines the therapeutic response to drugs and devices. Machii et

al,(58) showed that reverse remodeling occurred after treatment in patients with no LGE

and with LGE localized in inter-ventricular septum, but did not in patients with extensively

distributed LGE. Since LV segments with a lower amount of LGE are expected to have

more viable but functionally disturbed cardiomyocytes and reversible matrix fibrosis, they

are more likely to benefit from therapies. Bello et al also showed that myocardial

contractility improved in 56% with no LGE compared to 3% with LGE and concluded

that presence of LGE affects the response of heart failure patients to beta blocker. (17)

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CMR assesses mechanical dysynchrony. It also provides the location of myocardial

scar and coronary venous anatomy for optimal lead placement , which influence the

likelihood for success of CRT. (68,69) Multiple studies have shown that the extent of

myocardial scar, depicted as LGE is predictive of response to CRT.(70–72) On the above

of that , LV lead placement over the region of scar reduce the effectiveness of CRT. (70)

Bleeker et al demonstared lower response rates to CRT and no change in dysynchrony for

those with posterolateral scar (14% vs. 81%, p < 0.05) compared with those without . (70)

White et al reported that a LGE extent cutoff value of 15% of LV volume provided

sensitivity and specificity of 85% and 90%, respectively, for clinical response to CRT. (71)

Another study have shown that pacing in a site with >50% transmural scar was associated

with poor response to CRT.(72)

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AIM AND OBJECTIVE

Hypothesis:

1. MRI features of NIDCM helps in assessment ventricular function and also helps in

diagnosis.

2. Myocardial fibrosis, detected by MRI as late gadolinium enhancement (LGE) is a

marker of poor prognosis.

Aim:

To study the MRI features of NIDCM and its clinical correlation.

Study objectives are:

1. Global biventricular structural and functional assessment.

2. Differential diagnosis made out by MRI.

3. Late gadolinium enhancement (LGE) – prevalence and distribution pattern.

4. Clinical correlation of LGE with – Left ventricular (LV) function, Death ,

Sudden cardiac death (SCD), Arrhythmia, heart failure (HF)

hospitalizations

.

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MATERIAL AND METHODS

Study design :

A retrospective observational study.

Inclusion criteria:

All patients of NIDCM (decreased systolic function, i.e., LVEF < 50%) who

underwent CMR from 1/1/2012 to 31/12/2016 .

Exclusion criteria:

1. significant CAD (>50% luminal narrowing on coronary angiography and/or a

history of coronary revascularisation or myocardial infarction),

2. valvular disease

3. hypertensive heart disease

Follow up:

They were followed prospectively up to 31/6/2017 for clinical end points. Primary

end point was defined as occurrence of major cardiac end points (MACE). It includeed

all-cause mortality, sustained VT/appropriate ICD shock, sudden cardiac death (SCD)/

resuscitated cardiac arrest (RCA), and heart failure hospitalization. Secondary end points

were defined as occurrence of all-cause mortality, cardiac mortality, sudden cardiac death

(SCD)/ resuscitated cardiac arrest (RCA), sustained VT/ ICD shock and HF

hospitalization.

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Baseline demographic data of all enrolled patients were taken from medical records

including full clinical history, symptomatic status. Chest roentgenogram,

electrocardiogram, echocardiography details and CMR findings were also recorded.

Detailed Echocardiography was done prior to CMR with emphasis on the following

parameters:

1. LV dimensions- LVIDD, LVIDS

2. Ejection fraction – LVEF, RVEF

3. RWMA- present/ absent ; RWMA area

4. Diastolic Dysfunction- present /absent

5. Mitral regurgitation –present/absent

6. Tricuspid regurgitation- present/absent

7. Pulmonary hypertension- present / absent

8. RV dysfunction- present / absent

9. Dysynchrony - present / absent

Cardiac MRI Sequences:

Cardiac MRI was done with SIEMENS 1.5 T machine or a 3 Tesla system

(Discovery 750w; General electric GE healthcare; USA). Following cardiac MRI

sequences were used :

1. Cine – Steady state with free precession (Cine-SSFP) sequences (Short axis,

four chamber and two chamber views). It detects both regional as well as global

biventricular structure and function.

21 | P a g e

2. T2 weighted Short tau inversion recovery (T2w-STIR) – It detects free water in

myocardium, reflecting inflammatory changes.

3. Late gadolinium enhancement (LGE)- Late Gadolinium enhancement

was assessed using PSIR (Phase sensitive Inversion Recovery) sequences with an

inversion time of 200 ms, a repetition time of 8.5 ms, and an echo time of 3.5 ms,

after 20-30 min of intravenous injection of Gadolinium based contrast agent (0.2

mmol/kg body weight)

It detects tissue fibrosis/ scar .

a. There can be -

(i) LGE or no LGE

(ii) LGE pattern: Subendocardial/ midmyocardial/ subepicardial /

transmural enhancement .

(iii) LGE Distribution: focal / global / circumferential

4. Perfusion imaging - It was performed using three parallel short-axis sections in

end-inspiration. A fast GRADIENT echo sequence was used. Perfusion study used

0.05 mmol/kg of gadolinium at 4 mL/s followed by a 25 mL saline flush. Total scan

time was 1.4 mins.

5. T1-mapping – Generation of T1 maps for the quantification of decay in myocardial

signal intensity.

Following CMR the below parameters were studied:

1. LV size and morphology

i. LV ESV, LVESV/ m2

ii. LV EDV, LVEDV/m2

22 | P a g e

iii. LV SV , LV SV/m2

iv. LV EF

v. RVEDV, RVEDV/m2

vi. RVESV, RVESV/m2

vii. RV SV ,RV SV/m2

viii. RVEF

2. T2 w STIR – present/ absent

3. LGE-

i. Present/ absent -

ii. If present -

1. Pattern: Subendocardial/ midmyocardial/ subepicardial /

transmural enhancement

2. Distribution: focal / global / circumferential

LGE Quantification:

LGE was quantified by visual scoring method. (73). In a left ventricular 17-

segment model, each segment, was scored according to the percentage of enhancement

estimated visually. Score 0 was given for no enhancement, score 1 for 0% – 25%

enhancement, score 2 for 26% – 50% enhancement, score 3 for 51% – 75% enhancement

and score 4 for 76% – 100% enhancement. The global extent of LGE, “LGE score” was

calculated by adding scores from all 17 segments. LGE extent (volume) of LGE was

calculated as a percentage of the total score (4 × 17 = 68). So, LGE volume = 100 × (LGE

score) / 68 . It was expressed as % of LV volume.

23 | P a g e

Data collection:

The data was collected from medical records and follow up data was obtained from

their follow up visits in cardiology/cardiac surgery outpatient clinics or by telephonic

enquiry if there was no follow up visit in the last six months. All data was handled with

care to maintain patient confidentiality. Records were maintained in both computer and

paper formats. The closing point for any one patient will be the time of their last visit to

the follow-up clinic during study period.

Data analysis:

The data was analysed by the principal investigator with advice from a statistician.

Descriptive data were analysed by frequencies and categorical data by percentages , and

continuous variables by means and standard deviations. Continuous variables were

compared using Student’s t test (for parametric test) or Mann-Whitney U test (for non

parametric test) as appropriate. Group comparisons were done by χ2 tests. All statistical

analyses were done by the SPSS statistical software (release 23.0, SPSS Inc.; Chicago,Ill).

24 | P a g e

RESULTS

A total of 112 NIDCM patients were included in the study. Baseline characters are shown

in Table 1and 2.

Table. 1. Baseline characters (demography, risk factors, symptoms, ECG,

NTproBNP)

ALL (n=112)

Age (year)* 45.0 (31.25- 53.75)

Height (cm) 159.5 (± 14.4)

Weight (Kg) 61.45 (± 17.8)

BMI (Kg/m2) 24.1 (± 4.7)

Gender, Male 72 (64.3)

Diabetes Mellitus 29 (25.9)

Hypertension 12 (10.8)

Smoker 17 (15.2)

Alcoholic 7 (6.2)

Hypothyroid 9 (8.0)

Family history of DCM 4 (3.6)

Family history of SCD 4 (3.6)

NYHA Class 2 (2-3)

NYHA I 1 (0.9)

NYHA II 65 (58.0)

NYHA III 44 (39.3)

NYHA IV 1 (0.9)

NT pro BNP (pg/ml) 1560.0 (502.2- 3487.2)

NT pro BNP > 1000 pg/ml 32/52 (61.5)

ECG

SR 104 (93)

AF 5 (4.5)

VT 1 (0.9)

CHB 2 (1.8)

QRS

Normal 58 (51.8)

LBBB 39 (34.8)

RBBB 10 (8.9)

IVCD 3 (2.7)

QRS duration (ms) 100.0 (90.0- 160.0)

Holter

Normal 17 (74%)

AF/ AT 0 (0)

VT/ VF 4 (17.0)

VPC 2 (9.0)

Values are no. (%) or mean±SEM or median (IQR)

Abbreviations: DCM, dilated cardiomyopathy; SCD, sudden cardiac death; NYHA, New York

Heart association; CHB, complete heart block; NT pro BNP, N terminal pro brain natriuretic

peptide; IVCD, inter ventricular conduction defect

25 | P a g e

The median age was 45.0 years with inter quartile range of 31.25 years to 53 .7

years. Mean BMI was 24. 1 (± 4.7) kg/m2. Seventy two were male (64.3%). Twenty five

percent had diabetes mellitus while 10% had hypertension. Seventeen percent were

smokers. Nine patients (8%) were hypothyroid on treatment. Seven patients (6.2%) had

history of long term heavy alcohol intake (> 100- 120 mg/day). Family history of DCM

(ie,, two or more than DCM cases in first or second degree relatives ) was present in 4

patients (3.6%). Family history of SCD was present in 4 patients (3.6%).

Most patients had exertional dyspnea as the major symptom. Most of them were in

NYHA class II (58%) followed by NYHA class III (39.3%). One patient presented with

NYHA class IV. NT pro BNP during admission was done in 52 patients. Median NT pro

BNP was 1560 pg/ml. NT pro BNP value more than 1000 pg/ml was found in 32 out of

those 52 patients (61%) of them.

Most of the patients were in sinus rhythm (93%), while five patients had atrial

fibrillation, 2 had complete heart block and one presented with ventricular tachycardia.

LBBB was present in 35% of patients while RBBB in 9% and IVCD in 3% of cases. The

median QRS duration was 100mm (IQR: 90 - 160 mm). Chest X ray showed cardiomegaly

(cardiothoracic ratio >60%) in 74 patients (66.7%). Twenty four hour holter study was

performed in 23 patients, out of which 74% had normal study while 17% had VT and 9%

had VPCs.

Transthoracic echocardiography (TTE) was done in all cases and all measurements,

grading of lesions were done as per American society of echocardiography (ASE)

guidelines. TTE showed no mitral regurgitation in 12% of cases while mild, moderate and

26 | P a g e

severe mitral regurgitation were found in 65%, 17% and 5% respectively. So, majority of

patients had mild MR by echo. Similarly by transthoracic echocardiography pulmonary

arterial hypertension (PAH) was assessed. PAH was absent in 49% of patients. Fort two

percent had mild PAH , while moderate and severe PAH were present in only 9% and 1%

of patients respectively. Median LV ejection fraction was 32 %. Twenty five percent

patients had mild LV dysfunction (LVEF 40% to 49%), 12% had moderate LV dysfunction

(LVEF 40% to 35%) and 64% had severe LV dysfunction (LVEF < 35%). Both inter-

ventricular and intra-ventricular dysynchrony was present in 27% of patients.

Invasive right heart catheterization was performed in 70 patients. The median end

diastolic volume, end systolic volume and LV ejection fraction by cath study were 187 ml,

124 ml and 35% respectively. Fifty eight percent of patients by cath study had no PAH

while 35% had mild PAH and 7% had moderate PAH.

Most of the patients were in cardiac failure and treated according to existing HF

guidelines. (74) (Table 3). More than ninety percent of patients received ACE inhibitor /

ARBs, beta blocker, Mineralocorticoid receptor antagonist and diuretics. Digoxin was

prescribed in 70% of cases. Oral anticoagulant was given in 10 patients with AF and

CHADS2VAS2 >1. Permanent pacemaker inserted in 1 patient with CHB. Sixteen patients

received CRT out of which, 11 received CRT-P and 5 received CRT-D.

27 | P a g e

Table 2. Baseline characters (X ray chest, TTE, Cath)

ALL (N=112)

Chest X ray (Cardiomegaly) 74 (64.7)

Transthoracic echocardiography

MR

No MR 14 (12.5)

Mild MR 73 ( 65.2)

Mod MR 19 (17.0)

Severe MR 6 (5.4)

PAH

No PAH 54 (49.3)

Mild PAH 47 (42.0)

Mod PAH 10 (8.9)

Severe PAH 1 (0.9)

LV Function

Mild LV dysfunction 28 (25.0)

Moderate LV dysfunction 12 (10.7)

Severe LV dysfunction 72 (64.3)

LVEF (%) 32.0 (27.7- 40.0)

Dysynchrony 31 (27.7)

Cath study

EDV (ml) 187.5 (148.2- 222.2)

ESV (ml) 124.0 (93.5 – 171.0)

LV EF (%) 35.0 (23 -44)

PAH

No PAH 27 (58.6)

Mild PAH 16 (34.7)

Moderate PAH 3 (6.5%)

Severe PAH 0 (0)

Values are no. (%) or mean±SEM or median (IQR)

Abbreviations: MR, mitral regurgitation; PAH, pulmonary artery hypertension; LVEF, left

ventricular ejection fraction; EDV, end diastolic volume; ESV, end systolic volume; EF,

ejection fraction.

28 | P a g e

Table 3. Drugs and devices.

ALL

(N=112)

ACEI/ARB 107 (95.5)

Beta blocker 109 (97.3)

Spironolactone 106 (94.6)

Diuretics 100 (89.3)

Digoxin 78 (69.6)

Anti arrhythmic drug 16 (14.3)

OAC 10 (8.9)

DEVICES

PPI 1 (0.9)

CRT 16 (14.3)

CRT P 11 (9.8)

CRT D 5 (4.4)

Values are no. (%)

Abbreviations: ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor

blocker; OAC, oral anticoagulant; PPI, permanent pacemaker insertion; CRT (P/D), cardiac

resynchronization therapy (pacing/ defibrillator)

Cardiac MRI features:

Cardiac MRI with contrast was performed in all patients as per the protocol.

A) Structural and functional assessment:

LV was dilated in all patients. Volumetric analysis showed both increased end

diastolic volume (EDV) as well as end systolic volume (ESV). Median EDV, median ESV

were 100 ml/m2 BSA and 72 ml/m2 BSA, respectively. Median stroke volume was 27

ml/m2BSA and median LV ejection fraction was 28%. According to LVEF by CMR

majority had severe LV dysfunction (77%) . Only 12 % had mild and 11% had moderate

29 | P a g e

degree of LV dysfunction. Right ventricle dimensions were dilated in most of the patients.

RVEDV, RV ESV, RV SV, RVEF were 51 ml/m2, 32 ml/m2, 27 ml/m2 , 36%. RV

dysfunction (RVEF <40%) was present in 57% of patients. (Table 4)

Seventy five percent of cases showed no mitral regurgitation, while 19% showed

mild MR, 5% showed moderate MR and 2% showed severe MR. Majority of patients

showed no tricuspid regurgitation ( 93%) while 3.6% each showed mild and moderate TR.

No patients showed pericardial effusion.

Regional wall motion abnormalities, not accounting to any coronary vascular

territory was seen in 12 cases (10%). Dysynchrony was present in 13 cases (11%).

Perfusion defect, not accounting into any particular vascular territory was present in 13

cases (11%). T2-STIR images showing myocardial edema was present in 6 cases (5.5%)

out of which, 3 showed in the region of inter ventricular septum, one in inferior wall and

rest two showed globally. Two cases had organized LV apical clot.

30 | P a g e

Table 4: Cardiac MRI : structural and functional features.

ALL (N=112)

LVEDV (ml) 163.5 (124.0- 221.7)

LVEDVI (ml/ m2) 100.0 (77.5 – 144.0)

LVESV (ml) 120.0 (84.0- 171.0)

LVESVI (ml/ m2) 72 (52.0 – 111.5)

LVSV (ml) 44.0 (33.0- 55.2)

LVSVI (ml/ m2) 27.0 (21.5- 34.5)

LVEF (%) 28.0 (20.0 -35.0)

LV dysfunction

Mild LV dysfunction 14 (12.6)

Moderate LV dysfunction 12 (10.8)

Severe LV dysfunction 85 (76.6)

RVEDV (ml) 86.0 (60.0 -105.0)

RVEDVI (ml/ m2) 51.0 (40.0 -68.0)

RVESV (ml) 53.0 (36.0 – 74.0)

RVESVI (ml/ m2) 32.0 (21.0 – 46.0)

RVSV (ml) 27.0 (18.0 -36.0)

RVSVI (ml/ m2) 17.0 (11.0 – 23.0)

RVEF (%) 36.0 (26.2 -45.0)

RV Dysfunction 64 (57.1)

MR

No MR 84 (75.0)

Mild MR 18 (18.8)

Mod MR 5 (4.5)

Severe MR 2 (1.8)

TR

No TR 104 (92.9)

Mild TR 4 (3.6)

Mod TR 4 (3.6)

Severe TR 0

RWMA 12.0 (10.70)

Dysynchrony 13 (11.6)

Perfusion defect 13 (11.6)

LV Clot 2 (1.8)

T2-STIR 6 (5.5)

T2 –STIR area

Inter ventricular septum 3 (50.0)

Inferior Wall 1 (16.7)

Global 2 (33.3) Values are no. (%) or mean±SEM or median (IQR)

Abbreviations: MR, mitral regurgitation; PAH, pulmonary artery hypertension; LV, left ventricle ; RV, right

ventricle ; EF, left ventricular ejection fraction; EDV, end diastolic volume; EDVI, end diastolic volume

index; ESV, end systolic volume; ESVI, end systolic volume index; SV, stroke volume; SVI, stroke volume

index; TR, tricuspid regurgitation; RWMA, regional wall motion abnormality; T2-STIR, T2- short tau

inversion recovery.

31 | P a g e

B)Gadolinium contrast study:

Late gadolinium enhancement (LGE) was present in 44 cases (39.3%). Rest 68

cases were LGE –ve (60.7%). So, the prevalence of LGE +ve in NIDCM patients in this

cohort is 39%. (Table 5)

Table 5. LGE status.

LGE status

LGE +ve 44 (39.3)

LGE –ve 68 (70.7)

Values are no. (%) ; Abbreviations: LGE, late gadolinium enhancement

In majority of patients LGE distribution was predominantly found in mid

myocardium [33 cases (75%)], followed by sub epicardial not accounting into any coronary

vascular territory [6 cases (13.6%)], transmural [3 cases (6.8%)] and sub epicardial [2 cases

(4.5%)]. (Table 6) Pattern of LGE distribution were regional/ patchy in majority [33 cases

(75%)], followed by global/diffuse in 8 cases (18.2%) and circumferential in 3 cases

(6.8%). Considering the area of distribution, inter ventricular septum was the most common

site of LGE [38 cases (92.7%)], followed by inferior wall [23 cases (56%)], anterior wall

[21 cases (51.2%)], and least common in lateral wall [16 cases (40%)], though considerable

overlap occurred between different regions. If we look from base to apex , then most

common area of LGE distribution was mid part [36 cases (87.8%)] followed by base [27

32 | P a g e

cases (66%)] and apex [17 cases (40.5%)]. Bull‘s eye distribution model consisting of 17

segments showed that most common site of LGE positivity was mid IVS segments

followed by inferior wall , anterior wall and lateral wall. (Figure 1)

Table 6. LGE distribution pattern.

LGE Positive 44 (39.3)

LGE Pattern

Sub endocardial 6 (13.6)

Mid myocardial 33 (75.0)

Subepicardial 2 (4.5)

Transmural 3 (6.8)

LGE distribution

Global/ Diffuse 8 (18.2)

Regional /Patchy 33 (75.0)

Circumferential 3 (6.8)

LGE Area

Anterior wall 21 (51.2)

Inter ventricular septum 38 (92.7)

Inferior wall 23 (56.1)

Lateral wall 16 (36.3)

Base of LV 27 (65.9)

Mid of LV 36 (87.8)

Apex of LV 17 (40.5)

Values are no. (%)

Abbreviations: LGE, late gadolinium enhancement

33 | P a g e

Figure 1. Bull’s eye distribution of LGE in a 17 segment model. (Red colured numbers in

each segment represents percentage of LGE distribution in that segment)

Final diagnosis after cardiac MRI:

Idiopathic dilated cardiomyopathy was the most common form of NIDCM in this

cohort [83 cases (74%)]. (Table 7) Familial DCM present in 4 cases (3.6%). Myocarditis

was present in 6 cases (5.4%). LV non compaction was present in 5 cases (4.5%),

peripartum cardiomyopathy in 4 cases (3.6%). Drug induced cardiomyopathy was present

in 5 cases (4.5%) while end stage HCM in 2 cases (1.8%), sarcoidosis in 2 cases (1.8%)

and amyloidosis in 1 case (0.9%).

34 | P a g e

Table 7. Differential Diagnosis

Diagnosis No. (%)

Idiopathic DCM 83 (74.1)

Familial DCM 4 (3.6)

Myocarditis 6 (5.4)

LV Noncompaction 5 (4.5)

Drug induced Cardiomyopathy 5 (4.5)

Peripartum cardiomyopathy 4 (3.6)

End stage HCM 2 (1.8)

Sarcoidosis 2 (1.8)

Amyloidosis 1 (0.9)

Values are no. (%)

Abbreviations: DCM, dilated cardiomyopathy; HCM, hypertrophic cardiomyopathy.

35 | P a g e

Figure 2. Pie chart showing relative frequency (%) of different diagnoses of

NIDCM patients. (Abbreviations: DCM, dilated cardiomyopathy; HCM,

hypertrophic cardiomyopathy; LVNC, LV non compaction; PPM, peripartum

cardiomyopathy)

36 | P a g e

Idiopathic DCM:

Idiopathic DCM was the most common form of NIDCM. It was present in 83 cases

(74%). Familial DCM is present in 4 cases. The CMR features are dilated LV cavity with

increased EDV as well as ESV with decreased SV and EF. LGE was positive in 26 cases.

Most common distribution of LGE are patchy in mid myocardial region of IVS. (Figure 3)

Figure 3. CMR images of a patient with idiopathic dilated cardiomyopathy. Cine –SSFP

short axis image (A), four chamber view (B), and two chamber view (C) showed dilated

LV cavity. T2-STIR image (D) showed no myocardial edema present. 20 min LGE images

(E, F) showed mid myocardial enhancement in inter ventricular septum.

37 | P a g e

Myocarditis:

Myocarditis was diagnosed in 6 cases (5.4%). CMR showed dilated LV cavity. T2-

STIR images showed myocardial edema suggestive of ongoing inflammation. The

distribution of T2-STIR edema was mostly diffuse. LGE was present in all cases and the

distribution is diffuse mid myocardial or sub epicardial mostly involving the

interventricular septum or the lateral wall. (Figure 4)

Figure 4. CMR image of patient with myocarditis. T2-STIR image (A) showed

circumferential myocardial edema suggestive of inflammation. 20 min LGE image (B)

showed diffuse LGE of myocardium, involving circumferentially. CMR image of another

patient with myocarditis (C,D) showed dilated LV cavity with patchy mid myocardial, sub

epicardial LGE involving IVS, anterolateral wall.

38 | P a g e

LV Noncompaction (LVNC):

LVNC was diagnosed in 5 cases based on the Peterson’s critera. (75) According to

it, LVNC is diagnosed when the ratio of noncompacted myocardium to compacted

myocardium in diastole is > 2.3. LGE was positive in 3 cases, mostly distributed sub

endocardially in region of noncompaction. (Figure 5)

Figure 5. CMR images of a patient with LVNC. Figure A showing noncompacted region

and compacted region (blue arrow). The ratio between the two was >2.3. T2-STIR image

(B) showed no edema. 20 min LGE images (C,D) showed enhancement of subendocardial

and mid myocardial regions involving the non compaction.

39 | P a g e

Amyloidosis:

Amyloidosis is diagnosed in 1 case, whose CMR showed biatrialenlargement ,

thickened inter atrial septum and dilated LV cavity. LGE images showed circumferential

sub endocardial LGE. (Figure 6)

Figure 6. CMR image of a patient of amyloidosis. Cine –SSFP image (A) showed dilated

LV cavity, bi-atrial enlargement, thickened interatrial septum. 20 min LGE (B) showed

circumferential sub endocardial enhancement.

40 | P a g e

Sarcoidosis:

Sarcoidosis was diagnosed in 2 cases. Here CMR showed LGE in subepicardial

region with patchy distribution. (Figure 7) CT scan of chest showed enlarged hilar

lymphnodes.

Figure 7. CMR image of a patient with sarcoidosis. 20 min LGE images showed basal

and mid sub epicardial enhancement.

Chemotherapy induced DCM:

Chemotherapy induced cardiomyopathy was present in 5 cases. Four of them was due to

doxorubicin induced cardiomyopathy. All of them showed dilated LV with decreased LV

function. One case showed LGE in CMR. No one had myocardial edema in T2-STIR.

41 | P a g e

Peripartum cardiomyopathy:

Four cases had peripartum cardiomyopathy. CMR showed featurs like idiopathic DCM.

Onepatient showed LGE in CMR.

End stage (dilated stage) of HCM:

Two cases had end stage HCM. Their CMR images resemble that of dilated

cardiomyopathy. Both had LGE positivity.

Comparison between LGE +ve and LGE –ve group

The total cohort was divided into two cohorts based upon presence or absence of LGE

,i.e., LGE +ve group and LGE –ve group. They were followed prospectively for a mean of

745 ± 320 days.

Baseline characters:

All the base line features were similar in both groups except NT pro BNP values.

(Table 8 and 9) Median NT pro BNP was significantly higher in LGE +ve group (2934.0

pg/ml) compared to LGE –ve group (1095.0 pg/ml), p < 0.023. Similarly, NT pro BNP >

1000 pg/ml was present in significantly higher in LGE +ve group than LGE –ve group (

91.7% vs 52.5% , p= 0.018).

42 | P a g e

Table 8. Comparison of baseline characteristics between LGE +ve and

LGE –ve groups. (demography, risk factors, symptoms, ECG,

NTproBNP)

LGE+VE

N= 44 (39.3%)

LGE –VE

N= 68 (60.7%)

P value

Age (year) 40.0 (24.5-54.5) 45.5(33.0- 58.7) 0.285

Height (cm) 163.4 (± 9.3) 157.1 (± 16.4) 0.091

Weight (Kg) 63.4(± 13.3) 60.3 (±19.9) 0.502

BMI (Kg/m2) 23.6 (± 4.1) 24.3 (± 5.0) 0.549

Gender, Male 30(68.2) 42 (61.8) 0.548

Diabetes Mellitus 10 (22.7) 19 (27.9) 0.660

Hypertension 3 (6.8) 9 (13.4) 0.357

Smoker 7 (15.9) 10 (14.7) 1.000

Alcoholic 1 (2.3) 6 (8.8) 0.242

Hypothyroid 2 (4.5) 7 (10.3) 0.479

Family history of DCM 2 (4.5) 2 (2.9) 0.645

Family history of SCD 2 (4.5) 2 (2.9) 0.645

NYHA 0.365

NYHA I 1 (2.3) 0 (0.0)

NYHA II 27 (61.4) 38 (56.7)

NYHA III 16 (36.4) 28 (41.8)

NYHA IV 0(0.0) 1 (1.5)

NT proBNP (pg/ml) 2937.0 (361.5 -3345.0) 1095 (352.2- 3392.5) 0.023

NT pro BNP >1000

pg/ml

11/12 (91.7) 21/40 (52.5) 0.018

ECG 0.189

SR 39 (88.6) 65 (95.6)

AF 2 (4.5) 3 (4.4)

VT 1 (2.3) 0 (0.0)

CHB 2 (4.5) 0 (0.0)

QRS 0.074

Normal 24 (54.5) 34(51.5) 0.987

LBBB 11 (25.4) 28 (42.4) 0.105

RBBB 7 (15.9) 3 (4.5) 0.047

IVCD 2 (4.5) 1 (1.5) 0.875

QRS duration (ms) 100.0 (90 -150) 110 (98.5 – 160) 0.417

Values are no. (%) or mean±SEM or median (IQR);

Abbreviations: DCM, dilated cardiomyopathy; SCD, sudden cardiac death; NYHA, New

York Heart association; CHB, complete heart block; NT proBNP, N terminal pro brain

natriuretic peptide; IVCD, inter ventricular conduction defect

43 | P a g e

Table 9. Comparison of baseline characteristics between LGE +ve and

LGE –ve groups.(Xray chest, TTE, Cath)

LGE+VE

N= 44 (39.3%)

LGE –VE

N= 68 (60.7%)

P value

Chest Xray (Cardiomegaly) 29 (65.9) 45 (67.2) 1.000

Transthoracic

Echocardiography

MR 0.535

No MR 5 (11.4) 9 (13.2)

Mild MR 27 (61.4) 46 (67.6)

Mod MR 8 (18.8) 11 (16.2)

Severe MR 4 (9.1) 2 (2.9)

PAH 0.461

No PAH 20 (45.5) 34 (30.0)

Mild PAH 18 (40.9) 29 (42.6)

Mod PAH 6 (13.6) 4 (5.9)

Severe PAH 0 (0) 1 (1.5)

LV dysfunction 0.628

Mild LV dysfunction 13 (29.5) 15 (22.1)

Moderate LV dysfunction 5 (11.4) 7 (10.3)

Severe LV dysfunction 26 (59.1) 46 (67.6)

LVEF (%) 32.5 (27.0- 41.0) 31.5 (28.0- 36.2) 0.507

Dysynchrony 11 (25.0) 20 (29.4 ) 0.670

Cath study

EDV (ml) 187.5 (120.0- 235.5) 191.0 (167.5 – 220.5) 0.560

ESV(ml) 144.5 (74.7 – 194.7) 124.0 ( 100.0- 144.5 ) 0.887

EF (%) 23.5 (17.2 – 42.6) 35.0 (25.0- 39.0) 0.180

PAH 0.543

No PAH 7 (46.7) 20 (64.5)

Mild PAH 6 (40.0) 10 (32.2)

Moderate PAH 2 (13.3) 1 (3.2)

Severe PAH 0 (0) 0 (0)

Values are no. (%) or mean±SEM or median (IQR)

Abbreviations: MR, mitral regurgitation; PAH, pulmonary artery hypertension; LVEF, left

ventricular ejection fraction; EDV, end diastolic volume; ESV, end systolic volume; EF,

ejection fraction.

44 | P a g e

CMR features:

Table 10. Comparison of volumetric as well as functional parameters

assessed by CMR between LGE +ve and LGE –ve groups

LGE+VE

N= 44 (39.3%)

LGE –VE

N= 68 (60.7%)

P value

LVEDV (ml) 239 (168.0 – 369.0) 192.0 (136.0- 221.0) 0.827

LVEDVI(ml/ m2) 137.0 (87.5 – 225.2) 104.0 (77.0- 125.0) 0.677

LVESV (ml) 174.5 ( 123.0- 305.7) 124.0 (98.0- 160.0) 0.586

LVESVI (ml/ m2) 102.0 (63.7- 183.7) 79 (58.0 -91.0) 0.857

LVSVI 44.5 (40.5 -82.2) 53.0 (40.0 -60.0) 0.369

LVSVI (ml/ m2) 26.5 (21.2 -50.7) 29.0 (22.0- 34.0) 0.539

LVEF (%) 21.0 (13.2 -34.2) 27 (21.0 -32.0) 0.342

RVEDV (ml) 86.5 (59.0 - 142.0) 74.0 (57.0 – 97.0) 0.503

RVEDVI (ml/ m2) 49.5 (31.5- 86.0) 74.0 (57.0 – 92.0) 0.307

RVESV (ml) 64.5 (34.0 – 89.7) 47.0 (31.0 – 57.0) 0.103

RVESVI (ml/ m2) 37.0 (17.7 – 51.2) 30.0 (18.0 – 35.0) 0.087

RVSV (ml) 28.5 (21.2 – 57.5) 27.0 (24.0 – 35.0) 0.386

RVSVI (ml/ m2) 17.0 (10.0 – 34.7) 17.0 (13.0 – 19.0) 0.511

RVEF (%) 39.0 (31.2 – 47.5) 38.0 (36.0 - 46.0) 0.022

RWMA 12.0 (27.32) 0.0 0.001

Dysynchrony 7 (17.1) 6 (11.1) 0.548

T2-STIR 6 (13.6) 0 0.003

Perfusion defect 11 (25.0) 2 (2.9) 0.001

RV Dysfunction 30 (68.2) 34 (50.0) 0.078

LV CLOT 1 (2.3) 1 (1.5) 1.000

LV dysfunction 0.250

Mild LV dysfunction 6 (14.0) 8 (11.8) 0.777

Moderate LV dysfunction 2 (4.7) 10 (14.7) 0.121

Severe LV dysfunction 35 (81.4) 50 (73.5) 0.506

Values are no. (%) or mean±SEM or median (IQR)

Abbreviations: MR, mitral regurgitation; PAH, pulmonary artery hypertension; LV, left ventricle

; RV, right ventricle ; EF, left ventricular ejection fraction; EDV, end diastolic volume; EDVI,

end diastolic volume index; ESV, end systolic volume; ESVI, end systolic volume index; SV,

stroke volume; SVI, stroke volume index; TR, tricuspid regurgitation; RWMA, regional wall

motion abnormality; T2-STIR, T2- short tau inversion recovery.

45 | P a g e

Most of the functional and volumetric parameters were similar inboth the groups

with few exceptions. RV ejection fraction was significantly less in LGE +ve group

compared to LGE -ve group. Similarly RWMA, perfusion defect and T2-STIR edema is

significantly more common in the LGE +ve group.

Treatment received:

Table 11. Comparison of treatment received between LGE +ve and LGE

–ve groups.

LGE+VE

N= 44 (39.3%)

LGE –VE

N= 68 (60.7%)

P value

ACEI/ARB 43 (97.7) 64 (94.1) 0.647

BB 43 (97.7) 66 (97.1) 1.000

Spironolactone 42 (95.5) 64 (94.1) 1.000

Diuretics 37 (84.1) 63 (92.6) 0.532

Digoxin 29 (65.9) 49 (72.1) 0.532

Antiarrhythmic drugs 10 (22.7) 6 (8.8) 0.039

OAC 4 (9.1) 6 (8.8) 1.000

DEVICES

PPI 1 (2.2) 0 0.392

CRT 7 (15.9) 9 (13.2) 0.784

CRT P 2 (4.4) 9 (13.2) 0.195

CRT D 5 (11.3) 0 0.008

Values are no. (%)

Abbreviations: ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor

blocker; OAC, oral anticoagulant; PPI, permanent pacemaker insertion; CRT (P/D),

cardiac resynchronization therapy (pacing/ defibrillator)

46 | P a g e

Treatment received by both groups were not significantly different except

antiarrhythmic medications such as amiodarone , which was more prescribed in LGE +ve

group compared to LGE –ve group (p=0.039). This suggest higher incidence of

arrhythmias in LGE +ve group for which amiodarone was given for secondary prophylaxis.

(Table 11)

Follow up:

The mean follow up period was 745 ± 320 days with no significant difference

between two groups. The primary end point , combined major adverse cardiac event (

MACE, comprising all cause mortality, sustained VT, SCD/ RCA, appropriate ICD shock

and HF hospitalization) was significantly more in LGE +ve group than the LGE –ve group

( 72.7% vs 29.4%, p <0.0001). (Table 12).

47 | P a g e

Table 12. Follow up for outcomes between LGE +ve group and LGE –ve

group.

ALL

N=112

LGE+VE

N= 44 (39.3%)

LGE –VE

N= 68

(60.7%)

P value

Follow up period (days) 745 ± 320 742 ± 312 750 ± 332 0.349

MACE 52 (46.4) 32 (72.7) 20 (29.4) 0.0001

All-cause mortality 6 (5.4) 4 (9.1) 2 (2.9) 0.209

Cardiac mortality 5 (4.4) 4 (9.1) 1 (1.5) 0.048

Sudden cardiac death

(SCD)

3 3 (6.8) 0 (0) 0.023

Resuscitated cardiac

arrest

2 (1.8) 1 (2.3) 1 (1.5) 1.000

Heart failure

Hospitalisation

49 (43.8) 28 (63.6) 21 (30.9) 0.001

ICD shock 0 0 0 -

VT 8 (7.1) 6 (13.6) 2 (2.9) 0.031

AF/AT 10 (8.9) 4 (9.1) 6 (8.8) 1.000

NYHA class 2 (1-2) 2 (1-2) 2 (1-2) 0.130

Values are no. (%) or mean±SEM or median (IQR)

Abbreviations: MACE, major adverse cardiac event; ICD, implantable cardioverter

defibrillator; VT, ventricular tachycardia; AF/AT, atrial fibrillation/ atrial tachycardia;

NYHA, New York Heart association.

48 | P a g e

The secondary end points also showed significantly worse outcome in LGE +ve

group. There were six all case mortality among which 5 were cardiac mortality and one

was non cardiac mortality. (Table 12) The all-cause mortality is higher in LGE +ve group

than the LGE –Ve group, though statistically not significant (9.1% vs 2.9%, p=0.209). But,

cardiac mortality was statistically more in LGE +ve group than the other (9.1 5 vs 1.5 %,

p = 0.048). SCD occurred in 3 patients (6.8%) in LGE +ve group compared to no patient

in LGE–ve group (p= 0.023). History of resuscitated cardiac arrest was present in 2 patients

, 1 in each group. Sustained ventricular tachycardia was significantly more common in

LGE +ve group than LGE –ve group (13.6% vs 2.9%, p = 0.031). Heart failure

hospitalization was significantly more common in LGE +ve group than LGE –ve group

(63.6% vs 30.4%, p < 0.001). (Figure 8)

Kaplan-Meier survival curve were created for MACE and all individual out comes.

(Figure 9 &10). It showed significantly worst event free survival rate in LGE +ve group

in comparison to LGE –ve group (Log rank 15.64; p < 0.0001)

49 | P a g e

Figure 8. Graph showing difference in outcomes of LGE +ve and LGE –ve groups.

Values are number. Abbreviations: MACE, major adverse cardiac event; VT, ventricular

tachycardia

Figure 9. Kaplan –Meier survival curve comparing event free survival (MACE) between

LGE +ve and LGE –ve group , which shows significantly worse outcome in LGE +ve

group. (log rank 15.64, p< 0.0001)

50 | P a g e

Figure 10. Kaplan-Meier survival curve showing event free survival for VT, Cardiac

mortality and Heart failure hospitalization. All these showed significant worse event free

survival in LGE +ve group compared to LGE –ve group.

51 | P a g e

LGE QUANTIFICATION:

The median LGE extent in LGE +ve patients was 12% (4% - 32%). ROC curve

was created to know the best discriminator value of LGE extent for highest sensitivity and

specificity for event free survival. (Figure 11) The area under curve (AUC) of ROC curve

was 0.889 with p=0.0001. From this we got value of LGE extent > 14% of LV volume,

which was having 90.6% sensitivity and 84% specificity for predicting MACE.

Figure 11. ROC curve plotted for determining of LGE volume for occurrence of MACE.

Area under curve(AUC)= 0.889 with P < 0.001

LGE +ve group then subdivided into LGE > 14% and LGE < 14% of LV volume.

Thirteen patients (30%) had LGE < 14% and 31 (70%) had LGE > 14% of LV volume.

Three out of 13 (23%) had MACE in patients with LGE <14% while 29 out of 31 (93%)

52 | P a g e

had MACE in patients with LGE >14% of LV volume which was statistically significant

(OR 48.3 , p < 0.0001) (Table 13 and Figure12 )

Kaplan –Meier survival curve was plotted between patients with LGE> 14% and

LGE > 14% for occurrence of MACE (Figure 12). It showed significant event rate with

LGE > 14% group compared to the other group (log rank 11.4, p 0.001).

Table 13. Frequency of MACE in LGE +ve vs LGE –ve group.

LGE < 14% LGE > 14%

No MACE 10 2

MACE 3 39

Total 13 41

Values are no. Abbreviations: MACE, major adverse cardiac event.

Figure 12. (A) Bar diagram showing frequency of MACE between LGE +ve and LGE –

Ve group. (B) Kaplan-Meier survival curve showing significant difference in event free

survival rate between 2 groups (log rank 11.4, p < 0.001)

53 | P a g e

Cox regression analysis:

Table 14. Univariate Cox regression analysis for event free survival.

HR 95% CI P value

Age (year) 0.986 0.970 -0.986 0.079

Sex, Male 1.316 0.750 -2.3.9 0.497

BMI (Kg/M2) 0.634 0.864 -1.009 0.085

Diabetes Mellitus 0.900 0.461 -1.759 0.758

NYHA II, III 0.617 0.083 -4.585 0.637

NT pro BNP > 1000pg/ml 2.82 0.933 -8.54 0.050

Chest Xray , cardiomegaly 2.493 1.249 – 4.977 0.010

Antiarrhythmic drug therapy 2.002 1.047 – 3.828 0.036

CMR PARAMETERS

LVEDVI (ml/ m2) 0.998 0.985 -1.011 0.747

LVESVI (ml/ m2) 1.003 0.999 -1.007 0.089

LV SVI (ml/ m2) 0.972 0.957 – 0.998 0.001

LVEF (%) 0.962 0.933 – 0.993 0.015

RVEDVI (ml/ m2) 1.011 1.00 -1.022 0.051

RVESVI (ml/ m2) 1.013 1.002 – 1.024 0.024

RV SVI (ml/ m2) 1.001 0.958 – 0.998 0.035

LGE, PRESENCE 2.961 1.685 – 5.201 0.0001

LGE , EXTENT 1.059 1.035 – 1.083 0.0001

LGE VOLUME > 14% OF LV 6.176 1.873 – 20.371 0.003

T2-STIR 1.069 0.520 – 3.456 0.192

PERFUSION DEFECT 1.236 0.526 – 2.904 0.627

Abbreviations: HR, Hazard ratio; 95% CI, 95% confidence interval; NYHA, New York Heart association;

LV, left ventricle ; RV, right ventricle ; EF, left ventricular ejection fraction; EDVI, end diastolic volume

index ESVI, end systolic volume index; SVI, stroke volume index; LGE, late gadolinium enhancement ; T2-

STIR, T2- short tau inversion recovery.

54 | P a g e

Univariate Cox regression analysis was performed for detecting significant

unadjusted predictors of MACE (Table14) . Significant predictors of MACE were

cardiomegaly by chest x-ray, NT pro BNP > 1000 pg/ml at the time of admission, LV SVI,

LVEF, RV SVI, RV ESVI, LGE presence and LGE extent. Among these LGE extent> 14%

of LV volume was the strongest predictor of MACE ( HR 6.17, CI: 1.87 – 20.37, p =0.003).

Multivariate Cox regression analysis was performed for detecting the adjusted predictors

of MACE (Table 15). The best overall predictors of MACE were LGE > 14% of LV

volume and presence of LGE.

Table 15. Multivariate Cox regression analysis for event free survival.

HR 95% CI P value

LGE, PRESENCE 2.301 1.346 – 3.974 0.008

LGE VOLUME > 14% OF LV 8.894 2.618 – 28.856 0.0001

Abbreviations: HR, Hazard ratio; 95% CI, 95% confidence interval; LGE, late gadolinium enhancement.

55 | P a g e

DISCUSSION

In our study we included 112 patients of NIDCM after excluding all ischemic DCM

by coronary angiography. The median age is 45 years and majority are male (64%). So it

is a disease affecting young males more than females, in their 3rd and 4th decade. One fourth

of them were diabetic while other coronary risk factors were present in less than 15% of

cases.

History of long term heavy alcohol intake (> 110- 120 mg / day) was present in 7

cases. The exact dose and duration of alcohol intake to cause cardiomyopathy is still not

known. Though, alcoholic cardiomyopathy can have systolic or diastolic dysfunction, with

or without LV dilatation. It mimics idiopathic DCM morphologically.(76) So, in the

absence of any definitive evidence, we preferred them to keep in idiopathic DCM group.

Family history of DCM (at least 2 members in first or second degree relatives have

DCM) is present in 4 cases which were labelled as Familial DCM. They all resemble

morphologically idiopathic DCM.

Majority of patients were in NYHA class II followed by NYHA class III. Most of

the patients were in sinus rhythm while only 5 cases had AF. So, this suggest that incidence

of AF is not high in DCM patients. Thirty five percent showed LBBB and 9% showed

RBBB suggesting high incidence of bundle branch block in DCM patients which also may

aggravate existing LV dysfunction.

Chest X-ray showed that 65% patient had cardiomegaly (CTR >0.6 ). This

emphasizes the role of basic investigations in evaluation of DCM patients. Trans thoracic

56 | P a g e

echocardiography (TTE) is the most commonly performed basal investigation to diagnose

DCM. We found that majority of patients had severe LV dysfunction with EF < 35%.

Mitral regurgitation (MR) was present in 87% but mostly it was mild (65%). MR in DCM

patients is usually due to LV dilatation leading to coaptation defect (secondary MR), which

occurs in hugely dilated LV. Mancuso et al showed limitations of present American society

of Echocardiographic criteria in diagnosing as well as grading secondary MR. (77) By

TTE, 50% had no PAH while 42% had only mild PAH. This suggest that PAH is

uncommon in DCM patients unless in very advanced cases with severe diastolic

dysfunction. Dysynchrony was present in 27% of case signifying one important correctable

cause of LV dysfunction. Invasive right heart catheterization showed also dilated LV

dimension with poor LV function. The prevalence and pattern of MR and PAH matches

with TEE data with good correlation. Majority of patients were on guideline directed

medical therapy.

The “NEED” for CMR in DCM.

TTE is usually the first imaging test done for assessing cardiomyopathies. The

reasons are it is easily available, can be done quickly with good hemodynamic assessment

and also puts light on etiology. The disadvantages are high inter observer variability,

affected by patients body position and clarity of echo window and less role in tissue

characterization. So, CMR is now considered gold standard in the evaluation of

cardiomyopathies.The reason behind this are

57 | P a g e

(1) with highresolution, detailed three-dimensional (3D)images of cardiac and

thoracic anatomy without interference of body habitus

(2) accurate tissue characterization based on various T1W/ T2 W and LGE

techniques which helps in diagnosis as well as prognosis.

CMR features:

The LVEDV and LVESV were more than normal values suggesting dilated LV.

Mean LVEF was 28 %. Seventy six percent had severe LV dysfunction.

Mean RVEF was 36% and 57% of patients had RV dysfunction. So, it shows that

almost half of DCM patients have biventricular dysfunction. RV function carries an

important prognostic significance in DCM patients. Bourant et al showed that poor RV

function leads to increased MACE rates in NIDCM patients.(26)Groote et al ,also showed

RVEF as an independent poor prognostic indicator heart failure patients. (78)We also

found that RV stroke volume asan poor prognosis predictor . These findings also strongly

recommends for doing CMR in all DCM patients as CMR is the gold standard for RV

volume and function assessment which will help in risk stratification.

Regional wall motion abnormality (RWMA), not in any coronary artery territory

distribution was present in 12 cases (10%). Most common location of RWMA was IVS

followed by inferior wall and all of them had LGE. Eight of them were diagnosed as

idiopathic DCM and rest one each as end stage HCM, sarcoidosis, myocarditis and LVNC.

Though, 5 of those 12 cases(42%) had MACE, RWMA was not found to be marker of poor

prognosis both in univariate and multivariate model. Poyhonen et al showed RWMA in

upto 34% of cases and described RWMA as a marker of bad prognosis. (66) This difference

58 | P a g e

in observation can be explained by higher number of patients (39%) in the Poyhonen’s

study have RWMA active myocarditis, whereas in our case only 10% had RWMA and 5%

had active myocarditis.

Dysynchrony was present in 12% of cases which almost half compared to

dysnchrony detected by TTE. The reason can be explained by simultaneous ECG recording

and Doppler analysis in TTE , which is not possible in CMR. T2-STIR showing myocardial

edema was present in 7 cases. Majority had myocarditis and one case had sarcoidosis. This

tool helps in distinguishing active phase from chronic phase of disease. (72)

One important finding we got that perfusion defect was present in 12% of cases.

Most of these cases had LGE and the areas showing perfusion defect matches with the

areas showing LGE.There is not much data on perfusion defect in NIDCM in existing

literature.(79)This may suggest that microvascular abnormality may be an etiology leading

to myocardial damage and fibrosis. This concept is in research phase now. One perfusion

study using SPECT imaging in NIDCM showed that patients with perfusion defect had

poor cardiac outcome than patients who didnot have it. (80)

LGE-CMR:

Prevalence of LGE :

The prevalence of LGE in various studies varies from 12 % to 67%. (14,16,17)

There is no data from India. This study is perhaps the first study from India about CMR in

NIDCM .Prevalence of LGE in NIDCM patients in our study is 39% which is comparable

to the existing data.

Distribution pattern of LGE:

59 | P a g e

The pattern of LGE distribution in CAD ( sub endocardial) is distinct from that seen

in NIDCM , making it an important tool in determining etiology.(39)

Overall LGE most commonly found in mid myocardial location of IVS followed by inferior

wall , though it may vary according to diagnosis. Some groups reported only midwall

enhancement in NICM (16)whereas others , including us , have got different patterns of

enhancement. (59,64) Mc crohon et al (14) found 2 predominant patterns of LGE

distribution in idiopathic DCM. First, Mid myocardial (28%) followed by had

subendocardial or transmural enhancement (13%) not in the territory of a coronary artery.

The reason for this discrepancy is not very clear. Histological examination showed patterns

of fibrosis matching with all pattern of LGE. (81,82).The mid myocardial LGE was

correlated with the focal segmental fibrosis in an autopsy study.(83)

Distribution pattern of LGE helps in diagnosis of different forms of

NIDCM.(38,39). End stage HCM was diagnosed when a patient with h/o HCM presented

with echo/ MRI features s/o DCM. Both the two patients in our series had LGE in IVS,

inferior wall with midmyocardial to transmural involvement. Matoh et al showed that LGE

CMR helps in differentiating end stage HCM patients from DCM and also helps in risk

stratification. (43) Myocarditis showed LGE diffuse and predominantly subepicardial and

mid myocardial LGE. Sarcoidosis showed patchy subepicardial LGE with predilection for

basal segments and amyloidosis showed circumferential subendocardial LGE as described

in literature.(42,48,50)

Though clinical history and TTE helped in suspicion of the underlying condition,

the final diagnosis was only made out after CMR study. This credit goes to the unique

60 | P a g e

tissue characterization ability of CMR which is not there in TTE. (43). That’s why CMR

is now considered the gold standard for diagnosis of cardiomyopathies. (15)

Prognostic importance of CMR in NIDCM:

To know the prognostic significance of LGE we divided the patients based on

presence or absence of LGE. No baseline difference in baseline features, symptoms, CXR,

TTE, ECGwas notedexcept RBBB which is more common in LGE +ve group.NT pro BNP

value at admission was also more in LGE +ve group signifying they were more clinically

sick. Both groups received equal treatments except antiarrhythmic therapy which is more

often prescribed in LGE +ve group. It says that LGE +ve group had more incidence of

arrhythmias than LGE –ve group.

Sixteen patients received CRT. Among these, 5 patients received CRT-D and 11

CRT-P. All patients who received CRT-D were LGE +ve. This signifies that LGE +ve

group had more incidence of VT than the LGE –ve group.

Baseline CMR volumetric data showed, all the LV dimensions including LVEDV,

LVESV were tend to be higher and LVEF tend to be lower in LGE +ve group though

statistically not significant. The existing literature also had differential views regarding

this. Many studies showed increased LV dimensions and decreased LVEF in LGE +ve

group, arguing for more fibrosis leading to more remodeled LV. (3,16,25) But, many other

studies did not show any significant difference in LV dimensions and function between

LGE +ve and LGE –ve group. (64,67)This depends upon the type and extent of fibrosis.

In DCM patients , the previous histopatholgy studies showed fibrosis is of 2 types – either

diffuse ( interstitial) or segmental (replacement) fibrosis.LGE CMR can pick up the

replacement fibrosis with good resolution but, it’s poor in detecting the interstitial fibrosis.

61 | P a g e

All patients with RWMA and T2-STIR edema and majority of patients with

perfusion defect were in LGE +ve group. This suggests that LGE +ve group,which had

wall fibrosis also had more wall motion abnormalities, more myocardial edema and

perfusion defects . These may be different pathological spectrum of the same underlying

etiology.

On follow up, LGE +ve group showed significantly more adverse outcome

compared to LGE –ve group. The primary end point (MACE) and secondary endpoints

(cardiac mortality, sustained VT, HF hospitalization) were significantly more in LGE +ve

group than LGE –ve group. This clearly suggests that LGE in NIDCM patients heralds

poor prognosis. LGE +ve patients not only had more sustained VT, cardiac mortality but

also had more HF hospitalisations. So it increases both mortality and morbidity. In

Univariate analysis, presence of LGE is one of the major determinant of MACE (HR 2.96;

p< 0.00001).

We quantify LGE extent visually and from ROC curve found LGE extent > 14%

as the best discriminator with highest sensitivity and specificity to determine MACE. In

Univariate analysis, LGE volume > 14% of LV volume was the strongest predictor of

MACE (HR 6.176, p =0.003). In Multivariate analysis, after adjusting age, LV function

and other confounders , LGE extent > 14% of LV volume and LGE positivity were the

only two discriminators for MACE. This clearly showed that quantification of LGE adds

to the prognostication value of CMR in NIDCM patients.

In earlier studies the prognostic values of LGE in NIDCM has been clearly

documented.(16,64,3,25,67)Assomull et al.(16)correlated LGE with mortality and adverse

cardiac events and described LGE as the best predictor of SCD with hazard ratio of 5.4.

62 | P a g e

Wu et al. (64) also shown that LGE +ve patients had higher MACE (HF,

appropriate ICD shock, and cardiac mortality; 44%versus 8%; 𝑃 = 0.001;HR, 8.2; 𝑃 =

0.002). One recent metanalysis(65)has shown that LGE +ve NIDCM patients had higher

risk of all-cause mortality, HF hospitalization, and sudden cardiac death. This metanalysis

put foreword the concept of taking LGEas an independent entity for risk stratification of

NIDCM.

Shimuzu et al (63) were one of the earlier investigators to visually quantify LGE

volume in NIDCM patient. They showed that MACE was significantly higher in patients

with LGE extent of > 10% of LV volume compared to the patients with <10% of LV

volume ( 36% vs 2 % , Log rank , p = 0.0001). Similarly Poyhonen et al, (66) also visually

quantified LGE in NIDCM patients and showed that LGE volume > 14% of LV volume

was the best parameter to predict bad prognosis. We also found a LGE volume > of 17%

of LV volume as the best predictor poor prognosis.

LGE denotes focal fibrosis, which may promote re-entry mechanism leading to

ventricular tachycardia. Areas of fibrosis in NIDCM, detected by CMR as LGE were found

as substrates for inducible VT. (61)This concept is also supported by the data from ICD

patients showing more appropriate shock in LGE positive patients.(64)In addition, more

fibrosis also can change the mechanical property of myocardium causing loss of

ventricular compliance leading to increased incidence of heart failure . (84)

Based on our study we can say that LGE presence and quantification helps in

additional risk stratification in NIDCM patients. Currently ICD as a primary prophylaxis

is indicated only based on LVEF criteria.(85)ICD implantation as per LVEF criteria had

63 | P a g e

not shown any significant benefit in DEFINITE study. (86)LVEF, which is usually taken

as a measure of LV function has been accepted as best predictor of mortality in

NIDCM.(87) But LVEF was not found to be a predictor of ICDdischarge. (88) Our study

also showed that lower LVEF, though predicted MACE in univariate model , wasnot an

independent predictor of MACE in multivariate model. For this reasons, the criteria for

ICD implantation needs an urgent revision. LGE in CMR should be taken as an emerging

indication for ICD in NIDCM patients. (89)

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LIMITATIONS

This is a retrospective but with an observational- follow up study design. It is a

single center study. Only those NIDCM patients who underwent CMR were analysed ,

which may not represent the entire spectrum of NIDCM.

LGE- showed only focal or replacement fibrosis whereas it is poor in detecting

diffuse interstitial fibrosis. Hence LGE determined fibrosis underestimates the presence

and extent of the myocardial in NIDCM.(81) Pre- and post-contrast T1 mapping may

further improve this deficit.(90)

65 | P a g e

CONCLUSION

• Accurate volumetric measurement and functional assessment can be

done by CMR.

• Prevalence of LGE in NIDCM is 39%.

• Cardiac MRI helps in diagnosing various forms of NIDCM based on

distribution pattern of LGE.

• LGE positive patients showed significantly higher combined major

cardiac events including all-cause mortality, VT, SCD, heart failure

hospitalisations. Thus LGE is a poor prognostic marker in NIDCM

patients and LGE extent gives an additional prognostic information

beyond LVEF.

• Further research will be needed to determine whether therapy guided

by CMR findings can lower morbidity and mortality in NIDCM

patients.

.

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ABBREVIATIONS

ACEI Angiotensin converting enzyme inhibitor

AF/AT Atrial fibrillation/ atrial tachycardia

ARB Angiotensin receptor blocker

ASE American society of echocardiography

CHB Complete heart block

CI Confidence interval

CMR Cardiac MRI

CRT (P/D) Cardiac resynchronization therapy (pacing/ defibrillator)

DCM Dilated cardiomyopathy

EDV(I) End diastolic volume (index)

EF Ejection fraction

EMB Endomyocardial biopsy

ESV (I) End systolic volume (index)

HCM Hypertrophic cardiomyopathy

HR Hazards ratio

ICD Implantable cardioverter defibrillator

IQR Inter quartile range

IR-CE Inversion recovery- contrast enhanced

IVCD Inter ventricular conduction defect

IVS Inter ventricular septum

LGE Late gadolinium enhancement

LV Left ventricle

76 | P a g e

LVNC LV non compaction

MACE Major adverse cardiac event

MR Mitral regurgitation

NT pro BNP N terminal pro brain natriuretic peptide

NYHA New York Heart association

OAC Oral anticoagulant

PAH Pulmonary artery hypertension

PPI Permanent pacemaker insertion

PSIR Phase sensitive inversion recovery

RV Right ventricle

RWMA Regional wall motion abnormality

SCD Sudden cardiac death

SSFP Steady state free precession

SV (I) Stroke volume (index)

T2- STIR T2- short tau inversion recovery

TR Tricuspid regurgitation

TTE Transthoracic cardiomyopathy

VT Ventricular tachycardia

77 | P a g e

PROFORMA

Age :

Sex:

Hospital No:

Risk factors

DM

HTN

Dyslipidemia

Family h/o CAD

Family h/o SCD

Family h/o DCM

Smoking

Alcohol

Other risk factors (mention)

H/o Arrythmiaa(VT/AF)

Respiratory problem :

Other Systems:

Functional Class – NYHA 1, II, III, IV

ECG

Rhythm- SR/ AF/ VT

PR interval-

BBB- LBBB/ RBBB

QRS – Duration, Axis

78 | P a g e

LVH/ RVH

ST T changes

Q waves-

X-Ray-

CTR

PVH

PAH

Echocardiogram –

LV dimensions-

Ejection fraction -

RWMA

Diastolic Dysfunction

Mitral regurgitation

RV dysfunction

Others-

Holter study( if done):

CAG- Cath study:

Coronary status -

Cath study-

LV SP

LV EDP

PCWP-

PA-

LVangio-

RWMA

79 | P a g e

EDV-

ESV-

EF-

Cardiac MRI

LV size and morphology

LV ESV-

LV EDV

LV SV –

LV EF-

T1 mapping –

T2 w STIR –

LGE-

Present/ absent -

If present,Distrubation-

subendocardial/ midmyocardial/ subepicardial

Regional / Global

Diagnosis:

Idiopathic DCM

Amyloidosis

Sarcoidosis

Peripartum CMP

Takotusbo CMP

Myocarditis

Blood tests-

80 | P a g e

ESR

CRP

Trop T

Pro BNP

Virological markers

Autoimmune markers

Medications:

ACEI/ARB

BB

Aldosterone antagonist

Diuretics

Digoxin

Antiarrtymic ( Amiodarone)

OAC

Date of last visit :

Follow up :

Symptoms : NYHA I/ II/ III/ IV

Mortality: All cause mortality, CVS mortality

Any CHF:

HF hospitalizations

Any SCD/ aborted cardiac arrest

Device implantations – ICD/ CRT-P/ CRT- D

Arrhythmias / ICD/CRT- frequency of shocks

Mortality

Cause of death:

81 | P a g e

Details of death:

Other complications:

LGE +ve Vs LGE –ve:

LGE +VE LGE -VE

LV EDV

LVSDV

LVEF

NYHA CLASS

SCD/ ABORTED SCD

MORTALITY

ARRHYTHMIAS/ SHOCK

HF HOSPITALISATION

82 | P a g e

83 | P a g e

84 | P a g e

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