Sodium-glucose co-transporter 2 (SGLT2i) inhibitors were initially introduced as oral hypoglycaemic agents. These medications have demonstrated effectiveness in reducing hospitalisations for heart failure and offer mortality benefits for individuals with type 2 diabetes and cardiovascular disease. Left atrial (LA) dysfunction is now considered to play a major role in the pathogenesis of Heart Failure with preserved Ejection Fraction (HFpEF). SGLT2 inhibitors are proved to improve cardiac remodelling irrespective of glycemic profile and reduce Left Atrial Volume Index (LAVI) with treatment. The aim of the study is to determine the effect of SGLT2i on LA strain in patients with HFpEF. This is a descriptive follow-up study, conducted at Cardiology IPD & OPD, IPGMER and SSKM Hospital, Kolkata, which aims to evaluate the effects of SGLT2 inhibitors on patients with heart failure with preserved ejection fraction (HFpEF). It involves 50 patients presenting with HF symptoms and an H2FPEF score ≥6. The study includes a baseline assessment with detailed history, NT-proBNP levels, and echocardiography (including LV global longitudinal strain, LA strain, RV function, and diastolic parameters). After 6 months of treatment with SGLT2 inhibitors, patients will undergo a follow-up evaluation using biomarkers and electrocardiographic parameters like LV volumes, LV diastolic function, LV Global Longitudinal Strain, LA Strain. Statistical analysis was performed using SPSS, with significance set at a p-value ≤ 0.05. In our study, the mean age of the population is 61.64 ± 8.69years. 34% of the population had atrial fibrillation, 72 % were obese, 10% belonged to NYHA Grade III. 38% of the patients were given Empagliflozin and 62% were given Dapagliflozin. In our study, we found that treatment with SGLT2i resulted in significant improvement in LAVI from 48±2.4 ml/m2 to 41.8±2.9 ml/m2, peak LA strain and E/e’. Peak LA strain showed a negative correlation with NT Pro BNP level.
HFpEF is a heterogeneous group of disorders associated with significant morbidity and mortality. It has been linked with comorbidities like hypertension, obesity, diabetes, CAD, CKD and rarely, cardiac amyloidosis
Sodium-Glucose co-transporter 2 inhibitors (SGLT2i) are oral hypoglycaemic agents which act on the SGLT-2 proteins expressed in the proximal convoluted tubules (PCT). The SGLT2 inhibitors in the HFpEF were a class IIA recommendation in the previous guidelines
SGLT2 inhibitors are proved to improve cardiac remodelling irrespective of glycemic profile and reduces E/e' and LAVI with treatment
Strain imaging by 2DSTE provides accurate and quantitative assessment of myocardial deformation of cardiac chambers.Though in patients with HFpEF LV filling pressure is normal at rest, it may increase with exercise, and LA strain corroborates well with this exercise induced increase in LV filling pressure
As diastolic dysfunction is the main pathology in patients with HFpEF, this study looks for the effect of treatment with SGLT-2 inhibitors on diastolic functions in patients with HFpEF through the assessment of LA function by 2D- STE.
Determine the effect of SGLT2i on LA strain in patients with HFpEF.
To determine effect of SGLT2i on NT pro BNP level in patients with HFpEF.
To establish any correlation between NT pro BNP and peak
LA strain and also to establish between different diastolic functional parameters and strain parameters.
To determine effect of SGLT2i on LV diastolic function in patients with HFpEF.
To determine the effect of SGLT2i on LV GLS in patients with HFpEF.
To determine the effect on SGLT2i on RV function.
Patient presenting in cardiology IPD/OPD with symptoms of heart failure with H2FPEF score ≥6.
Acute coronary syndrome, stroke or transient ischaemic attack within 90 days
Acute decompensated heart failure
Pregnancy/lactation
eGFR<20ml/min/1.73m2 known allergic reaction to SGLT2i
Diabetic patients who are already on SGLT2i.
Considering prevalence of HFpEF is 5.2% in India with confidence interval keeping at 95% with margin of error 5% estimated sample size is 73. However, considering time constraints we opt to keep our sample size 50.
Patients with HFpEF meeting inclusion criteria and free from exclusion criteria will provide informed consent and undergo baseline assessments, including history, physical exam, NT pro BNP levels, and echocardiography ( for LA Strain, LVGLS, RV function, and diastolic function). They will then be treated with SGLT2 inhibitors for 6 months, after which biomarkers and echocardiographic parameters will be reassessed.
All the echocardiographic measurements were obtained according to current guidelines of the American Society of Echocardiography / European Association of Cardiovascular Imaging
LV End Systolic, End diastolic and Ejection Fraction were estimated using Simpson’s Modified Biplane Method.
LV diastolic function was determined using trans mitral inflow velocities, assessed by pulsed wave Doppler, the E/A ratio, and the pulsed(e’) diastolic velocity wave issue doppler.
The E/e’ ratio was calculated as the measure of the LV filling pressure.
PASP was assessed through the evaluation of peak tricuspid regurgitation velocity (TRV). PASP = RA pressure +4V2 , where V = TRV.
LVGLS (Left ventricular global longitudinal strain) was obtained by tracing endocardial borders manually and incorporating them in a software which calculated the regional average of the apical two chamber, four chamber and three chamber views of the 17 segments at an end-systolic frame.
Deformation analysis of the LA was performed by 2D STE on focused 4- chambers and 2-chambers, at a frame rate 60-80 frames/sec, using an automated software. The baseline LA strain reference was set at ventricular end diastole using R-R ECG gating.
Data will analyzed using the SPSS 20.0 software (IBM, NY, USA) Continuous variables will be represented as Mean, Standard Deviation (SD) or Coefficient of Variation (CV). Statistical significance of study parameters on categorical scale between two or more groups will be studied using the independent t-tests, Chi-square test or Fischer exact test P value of ≤ 0.05 will indicate statistical significance Correlation between two parameters will be studied using the Pearson/ Spearman Correlation coefficient. Regression analysis will be used wherever required.
Out of 50 patients, 36 % of the patients were in the age group 61-70 years followed by 34% in the age group 51- 60 years. The mean age of our study population was found to be 61.64 ± 8.69years. 56% of the patients were male, rest 44% were female. 44% patients had history of smoking, rest were non-smoker. Only 34% of patients had Atrial Fibrillation. Out of 50 patients, 38% of the patients were given the drug Empagliflozin and 62% of the patients were given Dapagliflozin. 90% of the patients were classified as NYHA Class II and only 10% were categorised as NYHA Class III.
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NT Pro BNP |
0 month |
50 |
651.116 |
28.576 |
0.001 |
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6 months |
50 |
625.836 |
44.7152 |
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P<0.05 --- significant difference in mean value
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E/e' |
0 month |
50 |
13.476 |
1.5404 |
<0.0001 |
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6 months |
50 |
10.466 |
0.9184 |
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P<0.05 Significant difference in mean value
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LVGLS |
0 month |
50 |
- 16.10 |
4.74 |
0.014 |
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6 months |
50 |
- 17.78 |
0.11 |
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P<0.05 - Significant difference in mean value
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LAVI |
0 month |
50 |
48.598 |
2.4453 |
<0.001 |
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6 months |
50 |
41.890 |
2.9005 |
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P value<0.05 Significant difference in mean value
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Peak LA strain |
0 month |
50 |
-12.9048 |
1.18543 |
<0.001 |
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6 months |
50 |
-17.6758 |
1.81224 |
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P value <0.05 Significant difference in mean value
Comparison between LVEF, TAPSE, RV strain, E/A, E/e', PASP, eGFR, SBP, DBP, BMI showed no significant difference at 0 month and 6 month.
A prospective study evaluated the effects of SGLT2 inhibitors (SGLT2i) on peak left atrial (LA) strain, left ventricular (LV) global longitudinal strain (GLS), right ventricular (RV) function, and diastolic function in patients with HFpEF. The mean age of the 50 patients was 61.64 ± 8.69 years, with a higher proportion (36%) in the 61-70 age group. The study population was predominantly male (56%) and obese (72%). At baseline, the mean NT-proBNP was 651 ± 28.57 pg/ml, which significantly reduced to 625.82 ± 44.71 pg/ml after 6 months (p=0.001).
LV GLS improved significantly from -16.10 ± 4.7 to -17.78 ± 3.1 (p=0.014), while LA strain also showed a significant improvement, from -12.90 ± 1.18 to -17.67 ± 1.81 (p<0.001).
However, RV function, assessed by TAPSE and RV strain, did not show significant changes. The diastolic function parameter E/e’ improved significantly from 13.4 ± 1.5 to 10.4 ± 0.9 (p<0.001), but E/A did not show any significant improvement.
There was no significant change in blood pressure (SBP: 148.8 ± 14.7 to 147.0 ± 14.0 mmHg; DBP: 85.8 ± 10.8 to 84.3 ± 10.1 mmHg). The BMI remained relatively stable, with a minor reduction from 29.8 ± 7.1 to 29.6 ± 7.2 kg/m². LAVI significantly improved from 48 ± 2.4 to 41.8 ± 2.9 ml/m² (p<0.001). eGFR remained stable, with no significant changes (66.4 ± 7.9 to 66.7 ± 5.2 ml/min/m²; p=0.808), supporting the renal safety of SGLT2i.
Correlation analysis showed positive correlations between LA strain and LV GLS, and between LAVI and E/e’, while peak LA strain negatively correlated with both LAVI and E/e’. These findings are consistent with previous studies. In terms of safety, no harmful effects on kidney function were observed, aligning with prior evidence of SGLT2i’s renal and cardiovascular protective roles.
A meta analysis of two major trials EMPA KIDNEY
This study assessed the effects of SGLT2 inhibitors in patients with HFpEF over six months. We found significant improvements in left atrial volume index (LAVI), peak LA strain, and E/e’, while no improvement was seen in E/A or RV function (TAPSE and RV S’). Although left ventricular ejection fraction ( LVEF) remained s t able, LV global longitudinal strain (LV GLS) improved significantly, accompanied by a notable reduction in NT-proBNP. Blood pressure (SBP, DBP) and pulmonary artery systolic pressure (PASP) showed slight, statistically insignificant decreases. Kidney function, measured by eGFR, remained stable. Correlation analysis revealed a negative correlation between peak LA strain and NT-proBNP levels, while peak LA strain positively correlated with LV GLS and LAVI, and negatively with both LAVI and E/e’.
The limitations of the study are as follows:
Non-randomised, single-centre design.
Modest sample size.
Relatively short follow-up period.
LA volume calculated using a two- dimensional method; three-dimensional measurement is more accurate.
Did not measure LA reservoir, LA conduit, and LA contractile strain separately, instead using peak LA strain.
Self.