Key Words: diabetic
cardiology, coronary artery disease
Diabetic Cardiology is a branch of Cardiology that is assuming
increasing interest among physicians, Cardiologists and
Diabetologists. The increasing awareness of the cardiac
problems that the diabetic patient faces has prompted a lot of
studies and increase in the literature regarding this branch.
In this treatise, we shall see in brief the cardiac problems
that are common to a patient with diabetes mellitus. In this
context it is appropriate to say that "diabetes is a
cardiovascular disease". [1]
The most common problems faced in diabetes mellitus are:
1. Coronary Artery Disease (CAD)
2. Dyslipidemia
3. Heart Failure - "Diabetic Cardiomyopathy"
4. Diabetic Autonomic Neuropathy - Cardiac
5. Peripheral Vascular disease
Heart Failure
Heart failure is two to five times more in diabetic males and
eight times more in diabetic females.{2} The approximate
prevalence of heart failure in diabetics of over 10 year
duration is 30%. In the DIGAMI study, 66% of deaths in the
first year were due to heart failure. In this context, a
"Cardiotoxic Triad" of Hypertension, Myocardial ischemia and
Diabetic Cardiomyopathy has been identified.[3] In
Diabetic Cardiomyopathy, the epicardial coronary arteries have
been found to be normal and the blood pressure is also normal.
Left ventricular dysfunction is seen in 50 - 60 % of
diabetics. Initially the patient develops diastolic
dysfunction and later goes into systolic dysfunction. Patients
with heart failure with a normal ejection fraction are termed
to have 'heart failure with preserved ejection fraction'. Most
patients have both systolic and diastolic dysfunction. A
diabetic with heart failure has to be evaluated for Coronary
Artery Disease (CAD) as revascularization can improve heart
failure in this subset of people. Endothelial dysfunction,
increased permeability of smaller coronary vessels due to
endothelial dysfunction, Renin Angiotensin Aldosterone system
(RAAS) and Sympathetic Nervous System (SNS) activation are
also contributory to the development of heart failure.
In diabetics with heart failure early detection and treatment
are important. Systemic hypertension is the most important
cause of heart failure in diabetics. Almost 75% of patients
with Type 2 diabetes mellitus have systemic hypertension. The
classical signs of heart failure may not be present,
especially in heart failure with preserved ejection fraction.
Dyspnea on exertion is the most prominent symptom in these
patients. A six minute walk test is vey revealing in
detection and assessing the progress of treatment in patients
with heart failure. The brain natriuretic peptide is 96%
sensitive and 72% specific for the detection of heart failure.
The treatment of heart failure in diabetics entails mainly a
good glycemic control. Thiozolidinediones are useful in early
stages of diabetes mellitus but not when the heart failure is
established owing to their propensity for fluid
retention.[3] The mainstay of treatment of heart failure
is the Angiotensin Converting Enzyme Inhibitors (ACEI) and the
Angiotensin Receptor Blocker drugs (ARB). Beta blockers,
especially the third generation ones like Carvedilol and
Labetolol, block the beta 1, beta 2 and the alpha 1 receptors.
Lastly, the diuretic drugs have their important role in the
management of heart failure in diabetics.
Diabetic Autonomic Neuropathy
Diabetic Autonomic Neuropathy or Cardiac Autonomic Neuropathy
in diabetics (CAN) is one of the most important and serious
complication of diabetes mellitus.[4] It is common and
often missed during the clinical evaluation of the patient.
Approximately, 20% of diabetics have autonomic neuropathy and
it may even precede the other complications of diabetes
mellitus. The cardiovascular manifestations of CAN are many.
Other manifestations in diabetic autonomic neuropathy are the
gastrointestinal, genitourinary, metabolic and pupillary.
The five year mortality in CAN is five times more compared to
the patients without neuropathy. One study has quoted the 2.5
year mortality with diabetes and CAN to be 27.5% and the five
year mortality to be 53%. In contrast, diabetics with no CAN,
have a five year mortality of only 15%. It has been
reported that 29% of the deaths in those with CAN are sudden.
The main clinical manifestations of CAN in those with diabetes
mellitus are:
1. Exercise Intolerance
2. Resting tachycardia
3. Intra operative cardiovascular lability
4. Orthostatic Hypotension
5. Silent myocardial ischemia (SMI) or the Cardiac
Denervation syndrome.
Resting tachycardia is the presence of sinus tachycardia in
patients who are totally rested and not on any drugs that can
alter the heart rate like beta blockers or parasympatholytic
drugs. [5] Intra operative cardiovascular lability is the
presence of severe hemodynamic disturbances like unprecedented
hypotension or sudden spurt of hypertension during general
anesthesia in patients undergoing major surgery. It is
increased 2 -3 fold in patients with diabetes.[6] Orthostatic
hypotension is the presence of a fall in systolic blood
pressure of 20 mm Hg or more and a fall in diastolic blood
pressure of 10 mm Hg or more after three minutes of assuming
the erect posture. Silent myocardial ischemia is the presence
of ischemic ECG changes without any clinical symptoms or a
positive treadmill stress test in the absence of symptoms
during the period of ischemia. [7]
An interesting corollary to this would be the question as to
whether we need to screen diabetics for Coronary artery
disease. The question also leads us to the next step as to why
we need to screen them if at all.
It is a known fact that the prognosis is worse in diabetics
with coronary artery disease than in those without. Screening
for CAD helps in risk stratification of patients. It also
motivates the patient to adhere to medical therapy. Those
patients with high risk feature on screening benefit by
revascularization. Screening also indicates the need to
intensify medical treatment with beta blockers or ACEI.
Once we are convinced of the need to screen a selected
population of diabetics, the next question is when to screen
these patients for CAD. Those patients who want to start a
moderate to high intensity exercise program and are at
increased risk of CAD as follows need to be screened. These
risks are:
1. Age more than 35 years
2. Age more than 25 years with diabetes mellitus more
than 10 years
3. Type 1 diabetes mellitus of 15 years duration.
4. Any additional risk factors for CAD
5. Existence of microvascular disease as Retinopathy or
Nephropathy
6. Presence of Autonomic neuropathy
7. Peripheral vascular disease
Silent myocardial ischemia (SMI) is another known and dreaded
complication of diabetes mellitus and need to be diagnosed
early in the course of the disease to prevent major adverse
cardiovascular events subsequently. The methods of diagnosing
SMI are as follows:
1. Treadmill stress testing
2. Nuclear stress imaging - SPECT
3. Dobutamine stress echocardiography
4. Screening for atherosclerosis by observing the Coronary
artery calcium score or assessing the Carotid intima medial
thickness.
The recommendations for management of SMI in patients with
diabetes mellitus are as follows:
In type 1 or 2 diabetes mellitus in patients with age >60
years or diabetes mellitus of >15 years duration, tests for
SMI are to be done.
- If found to have severe ischemia, coronary
angiography is advised. Beta blockers and ACEI are to be
started and the treatment with statins needs to be
intensified.
- If the ischemia is moderate to mild,
tailored medical treatment is advised.
- If no ischemia is detected, the patient is
screened for subclinical atherosclerosis and the treatment
with statins intensified appropriately.
Coronary Revascularization in Diabetes mellitus - Current
Concepts. [8]
Coronary revascularization in diabetes mellitus can be either
with a Percutaneous Coronary Intervention (PCI) or Coronary
Artery Bypass Surgery (CABG). We shall see the salient
demerits of both these modes of therapy.
Percutaneous Coronary Intervention (PCI)
Patients with diabetes mellitus have a high rate of in-stent
restenosis. The incidence with bare metal stents has been
quoted to be approximately 37%. Even with drug eluting stents,
diabetics have worse outcome and in-stent thrombosis was more
than in non-diabetic patients.
Coronary Artery Bypass Surgery (CABG)
The 30 day CABG mortality was higher in patients with diabetes
mellitus than in non-diabetic patients. The incidence of
sternal wound infections was also higher in patients with
diabetes mellitus.
PCI vs CABG
It has been reported that there is no significant difference
in mortality between PCI and CABG in non-diabetic patients. In
patients with diabetes mellitus the mortality was lower in the
CABG group (23%) compared to the PCI group (29%). CABG is
found to be superior to PCI in patients with diabetes mellitus
and multivessel disease in terms of MACE and mortality. The
European Myocardial Revascularization Guidelines suggest CABG
in all diabetics with extensive CAD.
Medical management vs Revascularization
In stable coronary artery disease, trials have shown that
diabetic patients who have no high risk features on coronary
angiogram may be managed with intensive medical treatment.
This would be an adequate and valuable strategy in these
patients than revascularization.
Acute Coronary Syndrome (ACS)
In Acute coronary syndrome, diabetic patients have a worse
outcome - both with ST elevation and Non ST elevation
myocardial infarctions. The 30 day mortality in them is higher
than in non-diabetics. Early invasive strategies seen in
studies (FRISC II, TACTICS) showed grater benefit for diabetic
patients in terms of risk reduction in 6 months as evidenced
by a decrease in death, myocardial infarction or
re-hospitalization for ACS. (Invasive vs Conservative
Strategy). Revascularization was definitely better in diabetic
patients compared to non-diabetics.
Clinical Recommendations in Diabetics with CAD
The clinical recommendations in patients with diabetes
mellitus in light of previous studies are as follows:
- Aggressive cardiovascular preventive strategies
and adequate control of blood sugar needed
- Multiple parameters used for a decision on when and how to
proceed to coronary revascularization based on various
factors as follows:
* Clinical presentation
* Team work and discussion
* Threshold for CABG should be low in diabetics
* Use of drug eluting stents recommended in diabetics
* Early invasive strategy is favored
* Potent platelet inhibitors like Prasugrel and Ticagrelor
maybe in favor.
References
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The incidence of congestive heart failure in type 2 diabetes
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3. David SHB. Heart failure: A serious and common comorbidity
of Diabetes. Clinical Diabetes 2004. 22: 61-65.
4. Aaron IV, Dan Z. Contemporary Reviews in Cardiovascular
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5. Ewing AJ, Clarke BF, Diabetic autonomic neuropathy, present
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6. Burgos LG, Ebert TJ, Asiddas C, Turner LA, Pattison CZ,
Wang-Cheng R, Kampine JP. Increased intra-operative
cardiovascular morbidity in diabetics with autonomic
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