The intrinsic capacity of the heart to respond to stretch with increased contractility, has been described over a century ago1,2. It is known that the response to stretch is biphasic with cardiac myocytes (CMs) showing an abrupt, immediate increase in force followed by a subsequent, slow force response (SFR) over a period of second to minutes. The rapid response is mediated by a change in myofilament affinity to calcium. In contrast, the SFR response is not well characterised. Evidence shows an increase in the magnitude of the systolic calcium transient is associated with the SFR3. However, the mechanistic basis for the SFR is not known. The stretch-activated ion channels are of the Piezo family are possible candidates. Piezo channels are non-selective cation channels with preferential affinity for calcium and have been found to be involved in stretch responses in several tissues and organs. Piezo is expressed in cardiac tissue but its role in the heart has not yet been explored. This study uses the Drosophilaas a model to test for a role for Piezo in the stretch response in the heart. We tested heart function from control and from Piezo knock-out (KO) mutants before and after exposure to mechanical stress. To mimic mechanical stretch we exposed the hearts to hypotonic shock, which leads to osmotic swelling and membrane stretch. We measured the magnitude of the systolic calcium transient in control and Piezo KO hearts and observed the effects of hypotonic shock. In isotonic solution Piezo KO hearts exhibited significantly larger (p<0.00001) systolic calcium transients (235.8±15 SEMEAN, n=8)and subsequent contractions than control hearts (86.03± 10 SEMEAN, n= 8). This increased systolic calcium amplitude was associated with a 54.3 ± 5.5% greater sarcoplasmic reticulum calcium content in Piezo KO hearts (p < 0.01, n=7). However, Piezo KO hearts failed to respond to hypotonic shock. In contrast to control hearts, which show a significant increase (67 ± 10%p < 0.01 n=18) in systolic calcium transient amplitude in response to hypotonic shock, Piezo hearts failed to respond (3 ± 4% n= 19). Interestingly, the percentage increase of the calcium transient in response to hypotonic shock recorded in control hearts was equivalent to the calcium transient amplitude in Piezo KO hearts under isotonic conditions. These data show Piezo is required in the calcium release-associated response to mechanical stress in the heart. We suggest that the enhanced calcium transient amplitude recorded in Piezo KO hearts in isotonic solution may result from compensatory mechanisms.