CARDIOVASCULAR JOURNAL OF AFRICA • Volume 35, No 2, May – August 2024 108 AFRICA and all the other groups (p < 0.001 for AMT vs control and EMPA groups, p < 0.01 for AMT vs AMT+EMPA). Discussion In this study, we investigated the effects on QT interval of the concomitant use of EMPA and AMT, which have different effects on Na and Ca metabolism in cardiomyocytes, and it was found that EMPA significantly inhibited AMT-induced QT prolongation. AMT-induced QT and QTc interval prolongations were measured in the first and second hours by ECG recording, and it was determined that EMPA significantly ameliorated these prolongations. EMPA exerts its antidiabetic effect by decreasing glucose absorption in the kidney proximal tubule as a result of its inhibitory activity in SGLT-2 channel.1 In the EMPA-REG OUTCOME clinical study, in addition to the antidiabetic effect of EMPA, it was shown that EMPA reduced all-cause mortality (including cardiovascular death) and hospitalisations caused by heart failure.2 Moreover, it was shown that EMPA reduced cardiovascular death and hospitalisation for heart failure in heart failure patients with or without diabetes mellitus. EMPA did not cause hypoglycaemia in patients without diabetes in the EMPEROR-Reduced trial.14 However, physiopathological explanation of this beneficial effect of EMPA on reducing cardiovascular mortality has not been fully achieved. In the literature, clinical studies revealed that EMPA reduced arterial stiffness, cardiac oxygen demand and albuminuria. Animal studies have shown that EMPA regressed left ventricular fibrosis/remodelling and it had positive effects on left ventricular systolic and diastolic function.15-22 Also, in cellular studies conducted with diabetes models, it has been shown that EMPA reduced the amount of cytosolic Na in myocytes by inhibiting the sodium hydrogen exchanger (NHE).3 EMPA was also effective in intracellular Ca balance by increasing the L-type Ca channel activity, the amount of sarcoplasmic reticulum ATPase (SERCA2a) protein and the levels of ryanodine receptor-2,4 regardless of its SGLT-2 inhibition. AMT is a TCA drug that can be used in many indications, Table 1. QT, QTc durations and heart rate for all groups at basal, first and second hour Variables Control Empagliflozin Amitriptilin Amitriptilin + empagliflozin p-value Baseline Qt (ms), mean ± SD 77.33 ± 9.02 78.33 ± 6.28 71.50 ± 5.68 73.33 ± 8.02 0.35 QTc (ms), mean ± SD 165.42 ±18.34 152.57± 11.07 163.11 ± 11.59 159.97 ±15.18 0.453 HR, mean ± SD 263.00 ± 39.38 230.00 ± 10.06 314.83 ± 42.48 287.50 ± 29.99 0.002 First hour Qt (ms), mean ± SD 73.50 ± 2.26 75.67 ± 4.27 108.67 ± 5.96A 90.33 ±5.39B < 0.001 QTc (ms), mean ± SD 166.63 ± 17.92 154.60 ± 20.43 227.45 ± 26.89A 179.40 ±17.63C < 0.001 HR, median (IQR) 335.50 (75.75) 245.00 (144.25) 248.50 (123.50) 232.50 (107.25) 0.279 Second hour Qt (ms), mean ± SD 78.17 ± 6.18 77.33 ± 7.31 106.00 ± 12.60A 87.83 ± 4.54C < 0.001 QTc (ms), mean ± SD 184.65 ± 12.86 171.63 ± 20.36 229.89 ± 19.83D 191.66 ± 10.93C < 0.001 HR, mean ± SD 335.83 ± 21.99 295.67 ± 30.54 288.67 ± 53.86 326.30 ± 36.97 0.118 Aamitiriptilin vs control < 0.001 Bamitriptilin + empagliflozin vs amitriptilin < 0.001 Camitriptilin + empagliflozin vs amitriptilin < 0.01 Dempagliflozin vs amitriptilin: 0.001. Fig. 3. ECG comparisons of all groups at basal, first and second hour. A. control, B. EMPA group, C. AMT group, D. AMT+EMPA group. Hour 0 1 2 QTc (ms) 240 220 200 180 160 140 120 Control AMT + EMPA EMPA AMT Fig. 2. QTc comparisons for all groups at the basal, first and second hours. A B C D
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