A prediction model was developed from the Aliskiren Trial in Type 2 Diabetes Using Cardiorenal Endpoints (ALTITUDE), a trial in T2D patients with albuminuria or cardiovascular disease.

The authors included 5,081 patients with baseline NT-proBNP measurement and no history of heart failure.

The model was developed using Cox regression and validated externally in the placebo arm of The Canagliflozin Cardiovascular Assessment Study (CANVAS), including 996 participants with TD2 and established cardiovascular disease.

In T2D, higher N-proBNP, troponin T and BMI were independent predictors of new-onset HF, including patients using SGLT2-inhibitors.

General Comments:

The concept of a higher N-proBNP, troponin T and BMI being independent predictors of new-onset heart failure is not a novel concept.

This study simply uses data from two existing clinical studies (ALTITUDE and CANVAS) to suggest that these biomarkers are also independent predictors of new-onset heart failure in diabetics, including patients using SGLT2-inhibitors.

This is a predictable outcome, therefore the novelty of this study is limited. It is not clear how this prediction model for new-onset heart failure will alter the clinical identification of patients at high risk of cardiovascular disease with T2D.

Specific Comments:

1) It is concluded that N-proNP was the strongest predictor for hospitalization for new-onset heart failure. This is not a novel finding.

2) Table 1 shows that patients in ALTITUDE study that had higher NT-proBNP were older, had a higher fat mass, were more hypertensive, had more CVD disease, had more diabetic neuropathies, has a lower eGFR, albumin and hemoglobin, and were on a different drug regimen. Again, this is an obvious finding.

3) It is suggested that observed and risk of new-onset heart failure did not differ (Supplemental Figure 1 and 2). However, there does appear to be a difference in Tertile 3.

Minor:

• p. 5, line 49: The abbreviation “DMII” is used without defining what it means.

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