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Stay InformedWhat are the unmet needs of heart failure in diabetic patients?
First of all, diabetes is closely associated with heart failure. As shown in this slide, diabetes is a stronger risk factor for heart failure than hypertension. This slide also shows the proportion of diabetic patients in Japanese heart failure registries. It shows that more than 30% of patients with heart failure have comorbid diabetes. These data demonstrate that diabetes and heart failure are very closely related. However, the majority of such patients are often asymptomatic. In our clinical study, we performed echocardiography on all of our outpatients and inpatients with diabetes. We discovered that approximately 20% of the patients were found to have asymptomatic cardiac dysfunction. As the condition is asymptomatic, it is hard to diagnose except for echocardiography. That is the major problem. However, I think echocardiography is not usually performed in diabetic outpatient care, and also, the measurement of natriuretic peptide levels, for example NT-proBNP level, is now scarcely measured at regular intervals. Meanwhile, various large clinical studies recently demonstrated that SGLT2 inhibitors are highly effective for the prevention of heart failure. As shown here, heart failure is fatal once developed, and the prognosis is poor. In stages A and B, no symptoms are seen, but from stage C, symptoms develop and usually progress onto heart failure, and eventually result in death. If the SGLT2 inhibitor is used in asymptomatic stages A and B, the development of heart failure can be suppressed. Based on current information, the Japan Diabetes Society and the Japanese Circulation Society jointly published a consensus statement on a regular screening test for heart failure in diabetic patients, as I show you now. In this statement, a regular screening test for heart failure is recommended by annual measurement of BNP or NT-proBNP, along with chest X-ray and electrocardiography.
What needs to be done to overcome the current challenges in Heart Failure prevention in T2DM?
Diabetologists now understand the risk of heart failure, and I expect that regular testing will be performed for heart failure as a common diabetic complication. Diabetologists have been regularly performing tests for diabetic complications such as nephropathy and retinopathy. Similarly, regular testing for heart failure or cardiac function is recommended in diabetic outpatient care. If diabetologists similarly perform regular tests for heart failure, for example measurement of natriuretic peptide, and perform early intervention with SGLT2 inhibitors for asymptomatic cardiac dysfunction at stage A or B or, promptly refer to cardiologist for any symptoms at stage C, it will help prevent the deterioration of heart failure. These measures would be very meaningful in addressing and hopefully preventing the heart failure pandemic that is of great concern in the future aging society in Japan.
What is the value of measuring natriuretic peptide in T2DM for a diabetologist?
In this consensus statement, it is recommended to regularly perform measurement of BNP or NT-proBNP level in diabetic patients on an annual basis. While echocardiography is quite difficult to perform at usual clinic settings, these tests require blood sampling only and can be performed easily in routine care. Especially, measurement of NT-proBNP level is performed with usual biochemical tests, so it will require only one blood sampling tube and small amount of blood. I think these are the benefits. For instance, shortness of breath with a short walk into the clinic, or nocturia, are not the symptoms of diabetes but may be because of the increase in natriuretic peptide level due to cardiac dysfunction. Therefore, I believe it is important to find these symptoms as early as possible. As I mentioned earlier, asymptomatic cardiac dysfunction is seen in a certain number of diabetic patients actually, and measurement of natriuretic peptide levels is important for early detection of such patients. If the measured levels are high, it is also important as a rationale for selection of drugs, that is, giving priority to use SGLT2 inhibitors for the treatment of diabetes. As shown in this flowchart, if multiple positive test results are seen, such as any symptoms, abnormal electrocardiography or chest X-ray results, and the BNP level exceeding 100 pg/mL or NT-proBNP level exceeding 400 pg/mL, the patient may already have Stage C or D heart failure. As I mentioned before, patients at these stages have a very poor prognosis, so they should be promptly referred to cardiologists.
How should clinicians interpret natriuretic peptide cut-offs in T2DM?
Regarding actual use of the natriuretic peptide levels, this slide shows the guideline by the Japanese Heart Failure Society. The BNP level of more than 40 pg/mL and NT-proBNP level of more than 125 pg/mL shown in pale orange here show that the patient may already have mild heart failure. Therefore, for these diabetic patients, early referral to cardiologists for detailed examination with echocardiography, etc., or, as I mentioned before, giving priority to the use of SGLT2 inhibitors, may be useful for prevention of heart failure. For early detection and early prevention of heart failure, the BNP level of 40 pg/mL and NT-proBNP level of 125 pg/mL should be used as a guide.
Which patient type should undergo regular measurement of natriuretic peptide testing for heart failure prevention?
As I mentioned before, for clinical study, we perform echocardiography in all of our diabetic outpatients and inpatients. Based on the results, we evaluate how to identify the patients with asymptomatic cardiac dysfunction from the clinical characteristics. And we found that the patients with the following clinical characteristics have high risk of heart failure and thus regular measurement of natriuretic peptide levels is strongly recommended. First is elderly patients (65 years or older). Next is female patients. And, patients with the disease duration of more than 15 years. And, patients who already have hypertension and ischemic heart disease. And then patients with left ventricular hypertrophy and left atrial overload found at regular electrocardiography. Those who have a history of paroxysmal atrial fibrillation may also have left atrial overload, so the natriuretic peptide levels should be measured. And, patients with so-called pulse wave. And, patients who have very high pulse wave velocity (PWV). I think those who have a PWV exceeding 1700 usually are at risk. And, patients with chronic kidney disease (CKD). The patients with eGFR of less than 60 are at high risk of heart failure in our study, so we strongly recommend them to undergo regular measurement of natriuretic peptide levels. Many patients characteristically have diastolic cardiac dysfunction preserved ejection fraction. Hypertension, CKD, and also arteriosclerosis are risk factors for heart failure preserved ejection fraction. So, these conditions should be carefully monitored. In addition, the natriuretic peptide levels should be measured in patients with these conditions.
How frequently should natriuretic peptide testing be done?
In order to monitor decrease in cardiac function as a complication of diabetes, the measurement of natriuretic peptide levels should be added to regular tests, just as we perform albuminuria test for nephropathy once every 6 months, or ophthalmological test for retinopathy regularly. There are two reasons. One is that there are patients whose symptoms worsen rapidly. In high-risk patients, especially elderly patients, the symptoms could rapidly deteriorate. So it would be beneficial to have the usual NT-proBNP level for evaluation in the acute phase. Another reason is something like the same in the case of nephropathy, I think. For instance, in the case of diabetic nephropathy, as the disease progresses from Stage 1 to 2 and 3, urine albumin level increases gradually. I expect a similar evaluation can be made in the case of heart failure. For example, the NT-proBNP level of more than 125 pg/mL can be defined as Stage 2, and the level of more than 400 pg/mL as Stage 3. In other words, if the NT-proBNP level is measured not only in symptomatic stages but at regular intervals, the change in NT-proBNP level over time can be perceived and any deterioration would be realized before symptomatic cardiac dysfunction.
