In the United States, more than 29 million adults have type 2 diabetes while 6.5 million have heart failure and these numbers are expected to rise over time. These conditions often occur together which severely affects patient’s outcomes, quality of life, and expenses due to their adverse outcomes.
In Pakistan, Cardiovascular diseases are a serious problem for both genders and affected 17.5% of the population, and females are more commonly affected.
Patients having diabetes mellitus are more prone to develop heart failure even when other risk factors like hypertension, age, hypercholesterolemia are adjusted, as compared to those without diabetes.
The Framingham Heart Study suggests that diabetes mellitus independently increases the risk of Heart Failure up to 2-fold in men and 5-fold in women compared with age-matched controls.
A recent study suggested that 44% of patients hospitalized for HF have diabetes mellitus and it is an independent risk factor for the development of heart failure.
Advanced age, hypertension, hyperlipidemia, coronary artery disease, family history, lifestyle, insulin use all are independent risk factors for developing heart failure in diabetic patients. If we consider individual diseases, heart failure is more lethal and has a poor prognosis so the priority of treatment lies in the management of heart failure in diabetic patients.
Risk Factors for Congestive Heart Failure and Diabetes:
Diabetics have increased risk of developing heart failure not only because of coronary artery because of improper glucose metabolism which causes structural and functional abnormalities in cardiac function.
The impaired cardiac glucose metabolism and the switch of glucose to FFA oxidation that occurs in the diabetic heart has a significant negative effect on cardiac contractility and functioning thereby inducing left ventricular systolic and diastolic dysfunction even in the absence of coronary artery disease (CAD) or structured heart disease.
The mechanism involved is decreased glucose transport and oxidation, increase in use of free fatty acid, decrease sarcolemmal calcium transport, and alterations in myofibrillar regulatory contractile proteins which leads to decrease in energy reserves and efficiency of heart function.
Hyperglycemia and insulin resistance impaired cardiac function by cross-links in collagen molecules due to glycation end products leading to increased fibrosis and myocardial stiffness. Diabetes mellitus significantly increases the risk of recurrent hospitalizations for heart failure and the duration of hospital stay in patients with heart failure, and it is associated with significantly higher mortality compared with those without diabetes.
Symptoms of heart failure in Diabetes Patients:
- Shortness of breath (dyspnea) when you exert yourself or when you lie down (orthopnea) you may wake up at night due to dyspnea
- Fatigue and weakness
- Swelling (edema) in your legs, ankles, and feet due to collection of fluid in a body
- Palpitations (rapid heartbeat)
- Persistent cough or wheezing with white or pink blood-tinged phlegm
- Very rapid weight gain from fluid retention
- Lack of appetite and nausea
- Chest pain if your heart failure is caused by a heart attack
It is not rare that Diabetes patients may not have any symptoms of heart disease in the initial stages. They may report vertigo, dizziness, sweating, and symptoms of an upset stomach. The astute physician does not miss these symptoms, however, if missed, the patient might die.
Important Investigations in patients with heart failure and Diabetes:
Diabetic patient with heart failure is investigated as follows
- Risk factor like diabetes, hyperlipidemia, hypertension, and IHD
- Medical History
- Family History of diabetes and heart diseases
- Symptoms of heart failure including atypical symptoms
- Cardiovascular and Respiratory Examination
- Blood Test N-terminal pro-B type Natriuretic Peptide (NT-proBNP)
- Chest X-ray
- Stress Test
- Cardiac computerized tomography (CT) scan
- Magnetic resonance imaging (MRI)
- Coronary angiogram
- Myocardial biopsy
The “New York Heart Association classification” of Heart Failure:
This classifies heart failure symptoms into 4 categories
Class I: No Symptoms with normal physical activity. Normal functional Status
Class II: Mild Symptoms with normal physical activity. Comfortable at rest. Slight limitation of functional status
Class III: Moderate Symptoms with less than normal physical activity. Comfortable only at rest. Marked Limitation of functional status
Class IV: Severe symptoms with features of heart failure with minimal physical activity and even at rest. Severe limitation of physical activity
The American College of Cardiology and Americal Heart Association Guidelines:
This stage-based classification system uses letters A to D. The system includes a category for people who are at risk of developing heart failure.
Stage A: Patients at high risk for developing heart failure in the future but no functional or structural heart disorder
Stage B: A structural heart disorder but no symptoms at this stage.
Stage C: Previous or current symptoms of heart failure in the context of an underlying structural heart problem, but managed with medical treatment
Stage D: Advanced disease requiring hospital-based support, a heart transplant, or palliative care.
Management of Congestive Heart Failure in Diabetes Patients:
The mainstay of treatment is diabetic control. Below are the effects of diabetic treatments on the risk of heart failure:
Effects of Diabetes Mellitus Treatments and the Risk of Heart failure
|Biguanide (Metformin)||Associated with better short-term and long-term prognosis in patients with Heart failure|
|Associated with reduced mortality in Heart Failure patients|
|Reduces cardiac hypertrophy by AMPK mediated repression of mTOR and as a consequence protein synthesis|
|AMPK activation by metformin can stimulate cardiac glucose uptake|
|Sulfonylureas (SU)||Originally thought to increase mortality|
|No definitive Cardiovascular outcome trial to evaluate cardiovascular safety of Sulfonylureas vs placebo or other diabetic agents|
|Meta-analysis reports no increased Cardiovascular risk with Sulfonylurea’s treatment vs metformin|
|A retrospective cohort study reported an increased Cardiovascular risk in patients on Sulfonylureas vs metformin or DPP4 inhibitor|
|No definitive Cardiovascular outcome trials examining Sulfonylureas in Heart failure have been conducted|
|Thiazolidinediones (TZDs)||Reports on effects of TZDs on Cardiovascular safety are conflicting.|
|Beneficial effects were anticipated given improvements in glycemic control, inflammatory biomarkers, Blood pressure, triglyceride levels, and HDL|
|The proactive trial showed no reduction in the cardiovascular outcomes in patients on pioglitazone|
|A meta-analysis reported an increased risk of Myocardial infarction with rosiglitazone|
|IRIS trial reported a lower risk of stroke and Myocardial infarction in patients on pioglitazone vs placebo|
|The occurrence of fluid retention and weight gain is a reproducible side-effect of TZD therapy, which precludes its use in NYHA III and IV heart failure.|
|Glucagon-like peptide-I (GLP-I) receptor agonist||Meta-analysis reports no increase risk in heart failure or hospitalization for HF among type 2 diabetics|
|A meta-analysis revealed a modest improvement in ejection fraction in heart failure patients|
|Trial of GLP-1 agonist in advanced HF revealed a trend toward increased hospitalization in the diabetes mellitus subgroup|
|Dipeptidyl peptidase 4 (DPP4) Inhibitors||SAVOR-TIMI-53 Trial reported a significant increase in hospitalization for heart failure in patients on saxagliptin vs placebo|
|EXAMINE and TECOS trials do not reveal increased HF risk|
|Experimental studies in humans and animals show improvements in cardiac function when GLP-1 was activated by DPP4 inhibitor|
|DPP-4 knock out mice showed induction of cardioprotective gene signature post-MI|
|Sodium-glucose co-transporter 1 and 2 (SGLT1 and 2) Inhibitors||SGLT2 improves cardiovascular risk factors (weight reduction, reduction in SBP, and improved lipid profile)|
|EMPA-REG OUTCOME trial reported a reduction in cardiovascular mortality and hospitalization from HF using empagliflozin|
|CANVAS trial reported similar results for canagliflozin|
|Meta-analysis of cardiovascular events in type 2 diabetics on dapagliflozin reported no increased risk for cardiovascular events|
|Insulin||Some observational trials have suggested a relationship between insulin use and HF risk|
|Cardiovascular outcome trial with long-acting insulin analogs do not demonstrate increased cardiovascular event rate or HF|
Management of Heart Failure in Diabetes Patients:
The management of stable heart failure is different compared to patients who are acutely sick. Acutely sick diabetes patients with heart failure require oxygen, diuretics, nitrates, and possibly morphine (to alleviate the dyspnea).
Stable patients with heart failure need medicines that have long-term cardiac beneficial effects and drugs that lower the death rates.
The important drugs that prevent cardiac re-modeling and are effective in the treatment of heart failure in diabetes include:
- ACE inhibitors: These drugs are considered as first-line in the treatment of patients with diabetes and hypertension, heart failure, or nephropathy.
- Enalapril, Captopril, lisinopril etc
- No interaction by Diabetes status
- The benefit of captopril was similar among non-diabetes Mellitus and diabetes mellitus.
- Angiotensin receptor blockers: Like ACE-I, Angiotensin receptor blockers are also considered as first-line in the treatment of patients with diabetes and hypertension, heart failure, and nephropathy. They are especially recommended in patients who are allergic to ACE-I.
- Valsartan, Losartan, Irbesartan, Olmesartan, Telmisartan, etc
- Valsartan improved the composite outcome in those with and without diabetes
- RAAS and Angiotensin Receptor Neprilysin Inhibitors: Neprilysin inhibitors are a novel class of medicines. These drugs are usually given in combination with valsartan (Sacubitril/ Valsartan) because of their association with angioedema. Neprilysin is an enzyme that degrades the atrial and brain natriuretic peptides. When Neprilysin is inhibited, the levels of ANP and BNP in the blood are elevated and the duration of their action is prolonged. These drugs cause diuresis in response to cardiac stretch and improve the ejection fraction and the rates of sudden cardiac deaths in patients with markedly reduced ejection fraction.
- Sacubitril (Usually co-administered with Valsartan as Uperio and Entresto)
- β-Blockers: These drugs reduce the cardiac workload.
- Bisoprolol, Carvedilol, and Metoprolol ER
- Similar reductions for mortality and hospitalization in DM and non-DM
- Mineralocorticoid receptor antagonist: These drugs inhibit the cascade of RAAS activation in patients with heart failure.
- Spironolactone and Eplerenone
- Ivabradine: Ivabradine acts on the SA node and reduces the heart rate without affecting cardiac contractility.
- Ivabradine significantly reduced cardiovascular death or HF hospitalization in patients with and without DM
- Implantable Cardioverter-Defibrillator/Cardiac Resynchronization Therapy
- Lifestyle Management
- Lifestyle management should be integral to the care of patients with DM and HF. DM is linked to obesity, inactivity, and poor dietary choices, which in turn are linked to cardiovascular diseases, including HF. Exercise can improve functional capacity for patients with DM and HF.
- Exercise is safe and beneficial in patients with HF and DM. Patients referred to cardiac rehabilitation should be counseled on the importance of adherence to training. In patients with HFpEF and obesity, many of whom also have DM, a combined diet and exercise program can improve functional capacity.
Congestive Heart Failure in Diabetes Patients may occur as a result of long-standing diabetes or as an unrelated disease. It is important that diabetes patients with heart failure may have subtle symptoms like fatigue and lethargy, dizziness, vertigo, and heartburn. Early diagnosis and treatment may save the person from long-standing complications and even death.