Clinical Profile of Afro-Caribbean Patients with Angiographycally-proven Non-ischemic Dilated Cardiomyopathy: A Case Series Discussion and Review of the Literature-Juniper Publishers
JUNIPER PUBLISHERS-OPEN ACCESS JOURNAL OF CARDIOLOGY &
CARDIOVASCULAR THERAPY
It has been reported that in Afro-Caribbean patients,
the most common cause of heart failure (HF) is non-ischemic dilated
cardiomyopathy (NIDCM). The clinical profile of patients with
angiographycally diagnosed NIDCM in this population is however, not very
well known. We undertook a cases control study to determine which
clinical characteristics and traditional cardiovascular risk factors are
associated or not with the outcome of angiographycally-proven NIDCM in a
population of Afro Caribbean patients utilizing a sample of our Heart
Failure with reduced EF (HFrEF) patient’s data base. Among 16 cases with
HFrEF (mean age 62 years old) we randomly determined 8 cases with
angiographycally -proven NIDCM (Group 1) and compare them with 8
controls with angiographycally-proven ischemic dilated cardiomyopathy
-IDCM (Group 2) . The subsequent analysis indicated that although male
sex was more frequent in Group 2 and Obesity in Group 1, a history of
Hypertension or Diabetes were not different in both groups. The cases
(Group 1) showed more reduced EF and more dilated Left ventricle than
the controls, but a history of old myocardial infarction in Group 2
turned out to be the statistically most significant variable. We
conclude that the presence or the absence of the most important
traditional cardiovascular factors (Hypertension and Diabetes) , which
have been described as strongly correlated with coronary artery disease ,
are not necessarily predictive of angiographycally-proven NIDCM in an
Afro Caribbean population with HFrEF.
Abbrevations: HF: Heart Failure; NIDCM: Non-Ischemic Dilated Cardiomyopathy; HFrEF: Heart Failure with reduced EF; PAHO: Pan American Health Organization; CNCDs: Caribbean epidemic of chronic Non-Communicable Diseases; IHD: Ischemic Heart Disease; IDCM: Ischemic Dilated Cardio-Myopathy; EMR: Electronic Medical Records; LVEF: LV Ejection Fraction; LVEDD: LV End Diastolic Dimension; IVS: LV wall thickness; CAD: Coronary Artery Disease; DCM: Dilated Cardio-Myopathy; PET: Position Emission Tomography; DM: Diabetes Mellitus; HOPE: Heart Outcomes Prevention Evaluation; CHF: Congestive Heart Failure
Introduction
Over the past 50 years, countries of the Caribbean
Region have experienced an Epidemiological Transition [1-4]. In fact,
data from the Pan American Health Organization (PAHO) suggests that the
Caribbean epidemic of chronic non-communicable diseases (CNCDs) is the
worst in the region of the Americas [5,6]. The overall epidemiology of
Diabetes and cardiovascular disease in the Caribbean has reviewed and
[7-9] highlights the high prevalence of Hypertension, pre-hypertension,
Diabetes Mellitus, Obesity and Dyslypidemia. An update of the prevalence
estimates for traditional CVD risk factors in Jamaica, the grater
English speaking Caribbean community of the Caribbean, has shown that
the prevalence of hypertension is 25%; diabetes, 8%;
hypercholesterolemia, 12%; obesity, 25%; smoking 15%. However there are
not many studies on the impact, characteristics and risk factors
associated in heart failure in the Caribbean.
Laljie [10,11] founded that most of the patients with
Heart Failure were over 65 years of age, female, never smoked
cigarettes, overweight/obese . About 82 % of this series were
hypertensive, 42 % were Diabetics, and 28 % had history of Ischemic
Heart Disease. Based on echocardiography studies
the etiology of Heart Failure was classified as hypertensive
heart disease (54 %), ischemic heart disease (IHD) (26%),
Dilated cardiomyopathy (3%) and Rheumatic heart Disease (2
%) . Systematic literature review among the Afro-Caribbean
populations and Caribbean immigrants living in UK, compared to
other ethnic groups studies [12] have shown that the prevalence
of coronary heart disease and peripheral artery disease is lower
in Afro-Caribbean populations: the prevalence of CHD ranged
from 0-7 % in Afro-Caribbean compared to 2-22 % in Caucasians.
Moreover between 211 Afro-Caribbean patients [13] the
most common cause of heart failure was non-ischemic dilated
cardiomyopathy in 27.5% (whites, 19.9%; P<0.001). Lower rates
of ischemic cardiomyopathy were observed (13% versus 41%;
P<0.001), and the fourth most common cause of heart failure
in Afro-Caribbeans was cardiac amyloidosis (11.4%) as 10% of
Afro-Caribbean patients attending a heart failure clinic in South
London have ATTR V122I cardiac amyloidosis. Currently, there is
not information about Caribbean patients with angiographycally
defined Non-ischemic Cardiomyopathy, accordingly, we sought to
characterize the clinical factors associated with angiographically
Non-ischemic cardiomyopathy in an cases series of afro
Caribbean population.
Observational case control study in which a group of
cases with angiographycally defined Non-ischemic Dilated
Cardiomyopathy (NIDCM) are compared to a group of controls
with angiographycally defined Ischemic Dilated Cardiomyopathy
(IDCM) with the aim to describe if exposure to traditional
cardiovascular risk factors has occurred more or less frequently
in cases than controls.
From our Heart Failure with reduced left ventricular ejection
fraction - HFrEF (< 50 %) patients data base, we identify a
case series of patients with clinical, echocardiographic and
angiographic diagnosis of NIDCM (Group 1, n=8) and compare
them with a group of patient with clinical, echocardiographic
and angiographic diagnosis of IDCM (Group 2, n=8). All patients
underwent coronary angiography at the Heart Institute of the
Caribbean Cath Lab. Patients with myocardial infarction within
30 days and patients with primary valvular heart disease were
excluded. Patients were considered to have cardiomyopathy
secondary to coronary artery disease if a significant coronary
stenosis 70% was present in one or more major epicardial
coronary arteries associated with a wall motion abnormality in
the dependent myocardial territory. Conversely, patients were
considered to have nonischemic cardiomyopathy if coronary
arteriography failed to reveal significant coronary artery disease.
The clinical variables from each patient were obtained from
our Electronic Medical Records (smart EMR ) including the age,
gender, history of Hypertension, Diabetes Mellitus, Dyslipidemia,
Smoking, Obesity and history of old myocardial infarction . In
addition echocardiographic variables including LV ejection
fraction (LVEF), LV end diastolic dimension (LVEDD) and LV wall
thickness (IVS) were also collected for the final analysis.
Case series involving a retrospective electronic medical
record review using descriptive quantitative and qualitative
analysis. Continuous variables were expressed as means ±
standard deviation and were compared using the Student’s t
test. Categoric variables are expressed as percentages.
A total of sixteen patients were evaluated during the study
period. After the initial patient evaluation and use of eligibility
criteria Eighth patients had angiographycally defined NIDCM and
eight patients had angiographycally defined IDCM to be included
in the analysis. The clinical characteristics of both groups are
shown in (Table 1). There were more females, more obese,
more dyslipidemia and slightly more smokers patients in the
nonischemic cohort than in the cohort of patients with ischemic
cardiomyopathy. More patients with ischemic cardiomyopathy
were men and they were slightly older, and had less reduced
LVEF than the NIDCM patients but the frequency of the most
important risk factors: Hypertension (75%) and Diabetes (50
%), commonly associated with CAD, were similar in both groups.
Finally, although patients with NIDCM had more severe heart failure with lower LVEF and showed more significant cardiac
dilatation. A history of myocardial infarction was more common
in the ischemic group.
The present cases series study was the first in our country
that have investigated the impact of coronary artery risk
factors in patients with angiography defined non-ischemic vs
ischemic dilated cardiomyopathy One attempts can be made to
hypothesize a cause and effect theory in the sense that although
both group of patients were exposed over their lifetime to the
same strong risk factors for CAD , they , potentially, can develop
the same outcome (DCM, dilated cardiomyopathy) but one group
can develop DCM with angiographycally normal epicardial
coronary arteries and the other DCM with angiographycally
abnormal coronary arteries. According to the recommendations
of current guidelines for chronic heart failure [14] invasive
coronary angiography should be considered in patients with
HF and intermediate to high pre-test probability of CAD and
the presence of ischemia in non-invasive stress tests (who are
considered suitable for potential coronary revascularization)
in order to establish the diagnosis of CAD and its severity. So
that an angiographic diagnostic approach to a patient with a
high probability for ischemic heart disease and clinical and
echocardiographic evidence of dilated cardiomyopathy looks
plausible and logical.
Patients with left ventricular systolic dysfunction are
commonly divided into two major groups-those with ischemic
and non ischemic cardiomyopathy. Ischemic cardiomyopathy, a
result of the complications of coronary artery disease (CAD), is
one of the most common causes of heart failure in the Western
world [15]. It has been reported that 60% of these patients
with Heart Failure do have coronary artery disease (CAD) [16],
however, in about 40% of cases, the etiology of heart failure
remains unclear even after coronary angiography as coronary
artery disease was ruled out or its extent could not explain
the obvious myocardial dysfunction. As previously mentioned,
recent studies have confirmed the clinical impression that
in Afro-Caribbean patients, the most common cause of heart
failure (HF) is nonischemic dilated cardiomyopathy [13]: Dungu
JN et al. reported that in a population of 211 Afro-Caribbean
patients, the nonischemic dilated cardiomyopathy was present
in 27.5% (whites, 19.9%; P<0.001), also lower rates of ischemic
cardiomyopathy were observed (13% versus 41%; P<0.001).
Although other possible etiologies such as cardiac
amyloidosis have been proposed and appear to contribute up
to 10% of Afro Caribbean patients with heart failure [13], it
is interesting to consider in our study group the possibility of
abnormalities in coronary flow: Impairment of coronary flow
reserve has been shown in patients with dilated cardiomyopathy
(DCM) despite normal epicardial coronary arteries [17].
Various methods have been used to measure coronary flow in
these patients, [18] including coronary sinus thermo dilution, intracoronary Doppler flow wire, position emission tomography
(PET), and trans-esophageal echocardiography. In all these
studies, it has been demonstrated that coronary flow reserve
is reduced in DCM patients. Besides, it has been reported
that reduced coronary blood flow reserve is associated with
unfavorable outcome in patients with DCM [19].
Most recently Yasar et al. [20] have shown that patients
with idiopathic DCM and angiographically normal coronary
arteries have higher TIMI frame counts for all 3 coronary
vessels, indicating impaired coronary blood flow, compared to
control subjects without DCM. In addition to epicardial disease,
microvascular coronary disease is also both widespread and
often under-recognized [21]. In our case series 75 % of the
both groups of patients were hypertensive and 50 % were
diabetics the epidemiology of cardiovascular disease in the
black population of the Caribbean is important as attempts are
made to understand the reasons for racial disparities in health
outcomes in developed countries. Over the past 50 years, the
Afro-Caribbean population (i.e., Caribbean people of African
descent) has undergone an epidemiologic transition; with
cardiovascular disease now ranked as the leading cause of death
in the region [22]. The Afro-Caribbean population currently
has a prevalence of cardiovascular risk factors between that of
African nations and the black population of the United States.
Afro-Caribbean women have a greater burden of
cardiovascular risk factors than Afro-Caribbean men. The high
prevalence of cardiovascular risk factors and the presence of
type 2 diabetes in Afro-Caribbean youth indicate that the current
epidemic of cardiovascular disease is likely to remain unabated
in the short to medium term [22]. Too few clinical trials of
cardiovascular disease or cardiovascular risk factors have been
conducted in the region: estimates of prevalence for traditional
cardiovascular disease risk factors have shown a prevalence of
Hypertension, 25 %; diabetes, 8 %; hypercholesterolemia, 12 %;
obesity, 25 %; smoking, 15 % . In addition, 35 % of Jamaican have
pre-hypertension, and 3% had impaired fasting glucose [23].
Therefore it is clear from an epidemiological perspective
hypertension is the most prevalent cardiovascular risk factor
in the Afro Caribbean population but it is also well know that
Hypertension is an antecedent of the vast majority of individuals
with heart failure in the community, as suggested by data
from the Framingham Study [24]. The classic paradigm of the
progression of hypertensive heart disease is that hypertension
does not lead to dilated cardiac failure unless there is interval
myocardial infarction or a preceding phase of concentric
hypertrophy (i.e., hypertension does not lead directly to a dilated
ventricular chamber). However, this may not be accurate. Blacks
who commonly have a non-ischemic cardiomyopathy attributed
to hypertension have heart failure onset at a relatively young age,
making it less likely that they had progressed from concentric
hypertrophy to a burned-out dilated cardiomyopathy during a
long latent period.
In aggregate, these data raise the possibility that hypertensive
patients can progress directly to dilated cardiac failure without
antecedent concentric hypertrophy [25]. Being that left
ventricular mass increases disproportionately in hypertension,
relative to the ability of the microvasculature [26] to perfuse
the hypertrophied myocardium both at rest and during exercise,
thereby proving to be a ‘set up’ for chronic sub endocardial hypo
perfusion. On the other hand it is known that Heart failure (HF)
is the most common cardiovascular complication of diabetes
mellitus (DM). Heart dysfunction in the diabetic population may
develop regardless of typical risk factors such as hypertension
and coronary artery disease. The cause of HF in diabetes is
certainly multi factorial in nature, but hyperglycemia and
insulin resistance seem to be the core factors [27] Studies have
suggested the existence of a Diabetic Cardiomyopathy.
Hamby et al. found that diabetes was present in 22% of
patients with idiopathic cardiomyopathy compared to 11% in
the control group [28] Functional changes occurring in diabetic
patients typically involve the impaired diastolic function of the
heart, that may precede the systolic dysfunction. There is also
a significant association of dilated cardiomyopathy with DM
[29]. Accordingly, changes typical for systolic dysfunction may
indicate an increased risk for the development of HF, particularly
in the presence of coexisting hypertension. Several hypotheses
have been proposed to explain the mechanisms responsible for
decreased myocardial contractility in the diabetic population.
These include metabolic disturbances, accumulation of AGE,
myocardial fibrosis, small vessel disease, impaired calcium
homeostasis, autonomic neuropathy and insulin resistance. It
has been observed that in diabetic patients the endotheliumdependent
dilatation of the epicardial coronary arteries is
impaired [27].
The results of the Heart Outcomes Prevention Evaluation
(HOPE) study indicate that microalbuminuria is associated
with significant risk for congestive heart failure (CHF) [30].
That is why it seems reasonable to perform echocardiographic
screening for HF in diabetic subjects with micro albuminuria.
So in our presented case series the question might be: is this a
Coronary Artery Disease Problem or a Hypertension Problem
or a Diabetes problem? Thus, even in heart failure patients
classified clinically as ‘non-ischemic cardiomyopathy,’ up to
a fourth may have evidence of CAD at autopsy. Also, ischemic
changes have been demonstrated on endomyocardial biopsies
in such patients. Indeed, such patients with so called ‘nonischemic
cardiomyopathy’ may develop clinical ischemic events
on subsequent follow-up, an observation that suggests that
coronary disease may not be just a ‘bystander’ in these patients.
The frequent presence if micro vascular disease detected
with PET scanning or with Doppler flow velocimetry in response
to stress in such patients further incriminates CAD as a potential
contributor to the ventricular dysfunction [31]. Finally, we
found that more obesity patients in the group of NIDCM which brings into consideration the issue of the Metabolic Syndrome.
The metabolic syndrome and its components, glucose
intolerance, T2DM, hypertension, dyslipidaemia and obesity
seem increasingly common in the Afro Caribbean community.
The prevalence of LV systolic dysfunction in obese patients with
diabetes and hypertension but no overt coronary artery disease
may be of the order of 30% [32] with women at slightly lower
risk than men. With such a high prevalence, and the availability
of successful treatments, it may be time to consider screening
initiatives to identify LV systolic dysfunction in diabetic patients,
in order to prevent the progression to overt heart failure.
The present cases series study was the first in our country
that have investigated the impact of coronary artery risk factors
in patients with angiography defined non-ischemic vs ischemic
dilated cardiomyopathy in a Afro Caribbean population. One
attempts have be made to hypothesize a cause and effect
theory in the sense that although both group of patients were
exposed over their lifetime to the same strong risk factors for
CAD , they, potentially, can develop the same outcome (DCM,
dilated cardiomyopathy) but one group can develop DCM
with angiographycally normal epicardial coronary arteries
and the other DCM with angiographycally abnormal coronary
arteries, however, further research is needed to refine the
clinical definition of non ischemic cardiomyopathy in the Afro
Caribbean population so physicians can appropriately prescribe
treatment and accurately predict outcome of Heart Failure in
this community.
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