Nonischemic dilated cardiomyopathy (NIDCM) is a disease that
primarily affects the cardiac muscle and is characterized by ventricular
chamber dilatation and contractile dysfunction in the absence of significant
coronary artery disease or abnormal loading conditions 1. Left ventricular
ejection fraction (LVEF) should be less than 50% or fractional shortening of
less than 25 % with normal or near normal left ventricular (LV) wall thickness.
These effects could extend to other cardiac chambers with the right ventricle
(RV) and both atria may also be dilated and dysfunctional 2. The incidence
and prevalence of NIDCM is generally increasing, but this can be in part due to
improved recognition or other factors. Worldwide, NIDCM has a prevalence of at
least 1 in 2500 adults, affects males more than females, the third most common
cause of heart failure and the most frequent reason for heart transplantation
3. Despite having better prognosis than ischemic heart failure, NIDCM is still
associated with significant morbidity and mortality either due to progressive
heart failure (HF) or sudden cardiac death (SCD). Despite therapeutic advances
in heart failure management, 5-year mortality remains as high as 20% 4. On
the other hand, many of those patients have marked improvement in the LV
systolic function at follow-up and those patients have an excellent outcome. Therefore,
Risk assessment in NIDCM is crucial for proper patient management with
implications on surveillance, treatment, and outcome. Currently, risk
stratification is mainly dependent on the assessment of LVEF, as exemplified by
its use as the key determinant of device implantation especially implantable
cardioverter defibrillator (ICD) and cardiac resynchronization therapy (CRT)
5,6 . Some of patients who had ICD implantation for primary prevention of SCD
showed significant improvement of the ejection fraction at follow-up to levels
that may preclude implantation of these devices.  LVEF is still an important prognostic factor
in NIDCM, but effective risk stratification remains challenging, particularly
with respect to SCD, which calls for identification of more independent
prognostic factors to enable clinicians to more accurately stratify patients
with NIDCM and subsequently tailor their management 7-10.

Data about NIDCM from the Middle East and Saudi Arabia is generally
scarce. In the HEARTS registry, which was the 1st heart failure registry in
Saudi Arabia and Arab countries, NIDCM constituted 16 % of the causes of heart
failure in the acute setting and 38 % in the setting of high risk chronic heart
failure patients referred to tertiary care heart failure clinics. It was
considered the second most common cause of heart failure in both the acute and
chronic setting after ischemic heart disease and before hypertension 11-13.
The Gulf Acute Heart Failure Registry (Gulf CARE) is a multi-center,
multi-national prospective study, comprising six Arab gulf countries plus Yemen
and including 5005 patients, has reported that NIDCM constituted 18 % of heart
failure etiologies and was also the second cause of HF after coronary artery
disease 14.

 

From the above registries and from our clinical observations,
dilated cardiomyopathy in GULF countries needs more focus, attention and
further studies due to the following:

1-     
It is a common and prevalent more
than expected as shown from the HEARTS and GULF CARE registries and from our
clinical observations, at least in tertiary care hospitals.

2-     
It starts early in life with dismal
impact on survival, quality of life and productivity.

3-     
The etiology is very diverse and not
yet completely clear. While some causes are easy to identify like Peripartum
cardiomyopathy for example, others are not like myocarditis, toxic
cardiomyopathy, familial and idiopathic causes.

4-     
High prevalence of use of illicit
substances and drugs like Captagon (amphetamine like substance) and alcohol in
young and middle aged HF patients may shed the light on these factors as
possible causes of cardiomyopathy in Saudi Arabia.

5-     
Despite the rate of recovery of the
ejection fraction (EF) is high in these patients, it is very variable. While
some patients have complete recovery of the EF and LV dimensions to normal
parameters, others have either partial recovery or progressive worsening of the
EF. We need to look at the rate and predictors of recovery of the ejection
fraction and subsequently explore the possible interventions that could
increase the rate of recovery of the EF.

6-     
Some of the patients who had ICD
implantation for primary prevention of SCD had recovery of their ejection
fraction to levels that may preclude implantation of these devices. This
observation may mandate the importance of risk stratification that is not
dependent only on the assessment of ejection fraction but also on other
parameters that my predict improvement of the systolic function.

7-     
Despite the diagnostic and imaging
facilities (like CMR) are available in most of the tertiary care centers in
Saudi Arabia, there is under usage of these facilities partially due to lack of
awareness of the treating physicians or absence of qualified reading
physicians.

With no doubt, NIDCM is a big and growing health burden in GULF
region and Saudi Arabia in particular, with many vague areas including the
details of etiology, the clinical features and the rate and predictors of
recovery of these cardiomyopathies, but this hypothesis needs to be tested. A
registry able to capture all the relevant clinical information of patients with
NIDCM would enable us to improve our knowledge on epidemiology and outcomes of
real world patients with this clinical condition in this region. Further,
specific questions of high clinical relevance could be answered using the
information collected in the registry. Accordingly, our objective is to study
the clinical characteristics, diagnostic and management strategies and outcomes
of patients with nonischemic dilated cardiomyopathy who are managed in the
inpatient and outpatient setting..

Methods

This registry is a prospective, multicenter, observational study of
patients with NIDCM in Saudi Arabia. We aim to collect data on the clinical
phenotypes, diagnosis, investigations, management strategies and outcomes
including mortality, hospitalizations and recovery of EF across a wide variety
of patients with NIDCM seen by cardiologists, heart failure specialists and
other specialists dealing with those patients.

NIDCM includes a large group of heterogeneous myocardial diseases
that are characterized by ventricular dilation and hypocontractility of the myocardium
in the absence of coronary artery disease or abnormal loading conditions including
hypertension, valvular and congenital disorders. In clinical practice and
multicenter HF trials, the etiology of HF has often been categorized into
ischemic or nonischemic cardiomyopathy. In the cardiology literature, the term
DCM is being used interchangeably with nonischemic dilated cardiomyopathy but his
approach fails to recognize that “nonischemic dilated cardiomyopathy” may
include cardiomyopathies due to volume or pressure overload, such as
hypertension or valvular heart disease, which we usually do not accept them as NIDCM
15. So we adopted the term NIDCM rather than DCM to include all the causes of
dilated cardiomyopathies other than ischemic, significant valvular diseases, congenital
disorders or hypertension. Also we put ejection fraction of ? 40% as the cutoff
to exclude any overlap with patients with heart failure and preserved ejection
fraction.

Study design

The study is designed to be a prospective, multicenter,
longitudinal observational study of the clinical, echocardiographic, imaging,
laboratory, management and outcome features of patients with NIDCM presented to
the selected centers in the Kingdom. Data will be collected by using a web
based system and the CRF will be accessed online.

Inclusion
criteria

– Patients above the age of 18 years.

– Patient willing and able to give informed consent.

– Patient is able to comply with all study requirements.

– Signs and symptoms of heart failure.

– Documented evidence of LV dilatation and systolic dysfunction
with EF ?40%.

– Data collection is prospective and all patients enrolled in the
registry must be consecutively assessed in the study center.

– Inpatients and outpatients are acceptable for enrollment.

– New and follow-up patients are eligible.

Exclusion
criteria

– Patients with known significant coronary artery disease (prior
MI, prior PCI or CABG, positive stress test for myocardial ischemia).

– Patients with known history of rheumatic heart disease.

– Patients with known other significant valvular heart disease
other than functional mitral regurgitation.

– Patients with long standing hypertension.

 Enrolment data

The following information will be captured for each enrolled
patient:

– Demographic characteristics

– Risk factors for cardiovascular diseases

– Data on familial cardiomyopathy

– Co-morbidities

– Precipitating factors of HF

– Clinical signs and symptoms

– Blood tests performed

– Use of invasive/ non-invasive diagnostic procedures

– Use of pharmacological treatments

– Use of non-pharmacological treatments

Follow-up data

A follow-up visit after 6 and 12 months will be scheduled for all
outpatients and for patients discharged after an admission with NIDCM and HF.
During the course of the year patients will be followed-up, according to the
usual practice of the centers.

Sample size

We aim to have a sample of at least 1000 patients, making it the
largest data collection on that disease in the region.

Recruitment and
enrolment

We will recruit all consecutive patients with confirmed NIDCM
assessed by a cardiologist taking part in the registry. Patients’ data will be
examined by the treating physician to check that they meet inclusion criteria.
Written or verbal versions of informed consent will be presented to the subject
detailing no less than: the exact nature of the study; the implications and
constraints of the protocol; and any risks involved in taking part. It will be
clearly stated that the patient is free to withdraw from the study at any time,
for any reason, without any effect on future care, and with no obligation to
give the reason for withdrawal.

Central
validation of the diagnosis

It is imperative to ensure that patients in the registry have NIDCM
rather than alternative diagnoses. Local Investigator should retain in their
documentation the discharge letters and the echocardiographic report of all
enrolled patients. The registry coordinating center will randomly select 20% of
enrolled patient for a central validation of the diagnosis. The coordinating
center will ask local investigators to send the documentation (discharge
letter, echocardiographic report and others) for centralized validation. The
discharge or the medical report and echocardiogram report will be sent to 2
members who will independently review the information provided. If they both
agree that NIDCM is present the case will be settled. If they disagree the case
will be discussed by 2 other members of the steering Committee. A consensus
between these 4 members will be sought.

Ruling out Ischemic etiology

Ischemic heart disease is an exclusion criterion and should be
ruled out in this study. All patients with prior history of myocardial
infarction, acute coronary syndrome (ACS), PCI or CABG will be excluded. For
other patients with risk factor (s) for CAD, coronary angiography should be
promoted to be the gold standard test to rule out CAD. For low risk patients
other noninvasive modalities like myocardial perfusion scans, stress
echocardiography, CT angiography and cardiac magnetic resonance imaging can be
considered. 

Echocardiography

Echocardiography is an accurate and reproducible method for
assessing left ventricular size and function in normal-sized hearts without
segmental myocardial disease. Directly measured and derived M-mode left
ventricular parameters correlate well with invasively obtained data. Mandatory
Echocardiography parameters: LVEDD, LVESD, EF, FS, presence of MR and TR. More
detailed echocardiography parameters can be entered including details of
trans-thoracic, M-mode, 2-dimensional, and tissue Doppler echocardiography
(TDI) will form part of the comprehensive assessment of patients, by an
experienced echo-cardiographer, at the intervals defined above. The focus will
be on assessment of both the left ventricular dimensions and function.

Cardiac MRI (CMR)

Many tertiary care centers in Saudi Arabia have this imaging
modality. We will include CMR data related to tissue characterization and will
encourage participating centers in the registry to request this test if
available.   

Outcome measurements

Primary outcomes

– Mortality at 1 year.

– Cardiac transplantation or LVAD at 1 year

Secondary outcomes

– Improvement in New York Heart Association Functional Class at one
year.

– Readmission to hospital at 1 year.

– Improvement in left ventricular function (ejection fraction) by
echocardiographic evaluation at follow up visits.

Medication and
Interventions

Data will be collected on:

– Acute patient hospitalized (clinical course / medical treatment
in hospital).

– For ambulant patients (medications and devices).

Statistical
considerations

Statistical tests may be carried out for exploratory purposes, as
appropriate. Continuous variables will be summarized using means or medians
based on the normality; normally distributed variables will be summarized using
the mean and standard deviation (SD), while the non-normally distributed
variables will be summarized using the median and interquartile range (IQR).
Categorical variables will be summarized using frequencies and percentages.
Multivariable analyses may be used to explore relationship between baseline
covariates and post-baseline outcomes, as appropriate. The study being fully
observational, a formal sample size is not calculated. However, a sample of
1000 enrolled patients has been estimated to be good enough to give us a good
view of the primary and secondary outcomes.

Study
organization 

The principle investigators are responsible for the formulation of
the study protocol and to oversee its implementation. The steering committee
members are the sites principle investigators and they are key persons in
research in cardiology and heart failure in Saudi Arabia. 

Center and participating centers coordinators are responsible for
proper communication between different centers at all levels of data
collections and analysis. Persons assigned for data collections should be
experts in this field and include qualified nurses, physician assistants,
clinical pharmacists and research assistants. The principal investigators and
steering committee team has to assure the constant quality control and
continuity, necessary to ensure that the projects is completed on time and
within the budget. The investigator centers are contacted and accepted on a
voluntary basis. A specific Case Report Form (CRF) will be distributed both in
hard copy and web based to all centers with specific user name and password.
Each center will have to fill in CRFs of consecutive patients. Each
participating hospital will have a local principle investigator (LPI) who has
been chosen by the study principle investigator (SPI). It is the responsibility
of the LPI to ensure the accuracy of the data collected, and the timely and
complete entry of the data points into the e-CRF. In addition, the LPI will
designate research assistants (RA) who will either collect or supervise the
collection of the Data.

Each patient will be assigned a unique study number, and all
identifiers will be encrypted.  Quality
control procedures for this study include source data verification by randomly
selecting 20% of registry participant records with comparison between the paper
case report form (CRF) and the electronic database record of those same
data.  If errors are common, data will be
completely checked prior to data analysis. 

Duration of the
study

It is anticipated that approximately 1000 patients will be enrolled
within 1 year. There is no maximum number of patients per center. Follow-up
will be performed by the local investigators 6 and 12 months after enrolment.

Ethical issues

Site investigators will be responsible for obtaining the approval
of the local review boards for this registry, if necessary. All patients will
be approached by local center investigators and will be asked for their written
or verbal informed consent to participate in the registry (if necessary, i.e.
based on local standards). This registry is an observational study that does
not dictate the manner in which patients are evaluated or treated for NIDCM.
Physicians may decide to evaluate and manage patients with NIDCM in the most
appropriate way, according to the local standard of care. There is no selection
of patients and it is necessary to obtain patients’ agreement. In case of
refusal, the patient will not be enrolled in the registry. Patients’
identifiable data will be stored on local computers in order to facilitate
subsequent follow-up of patients.  Patients who cannot provide the informed
consent at the time of admission due to very severe clinical conditions can
give their consent some hours/days after admission, when more favorable
clinical conditions allow them to receive the appropriate information. Patients’
data collected will be strictly confidential. In order to maintain strict
security, each investigator/ study personnel will have a unique login and
password to enter patient’s information. There will be no storage of clinical
data outside of the data collection instrument, which will be a secure,
web-based form. The main database will be secured according to current
standards to ensure both ethical and integrity requirements of the data.

Publication
policy

Data will be published under the responsibility of the both the
principal investigators and the steering committee. Requests for further
analyses to support further publications must be submitted to the principal
investigator for approval. Any publications as a result of this study will be
considered a joint publication by the principal and co-investigators.
Contribution of the author to the study design, enrolment, data review, and
manuscript preparation and review will be considered when determining the order
of authorship. After the publication of the main paper, the database is
available for further analyses to all participating Investigators. The
Executive Committee must receive a copy of any presentation, manuscript, or
abstract prior to dissemination.

Written by
admin