System and methods for predicting drug-induced inotropic and pro-arrhythmia risk

1. A method for predicting a drug-induced pro-arrhythmia risk in connection with an at least one drug that has been administered to an at least one isolated primary adult cardiomyocyte from a human heart, based on an at least one after-contraction transient (“AC”) associated with the at least one cardiomyocyte, the method comprising the steps of:

implementing an at least one monitoring device positioned and configured for measuring data related to the at least one cardiomyocyte, wherein the at least one monitoring device is an optical device positioned and configured for measuring visual data associated with contractions of the at least one cardiomyocyte;

implementing a user application residing in memory on an at least one computing device, the at least one computing device configured for receiving and processing select data obtained by the at least one monitoring device;

measuring, via the at least one monitoring device, the effect of the at least one drug on the at least one cardiomyocyte;

determining, via the user application, the at least one drug has taken effect on the at least one cardiomyocyte;

applying a controlled external electrical stimulus to the at least one cardiomyocyte;

measuring, via the at least one monitoring device, a sequence of at least 60 sarcomere contraction transients of the at least one cardiomyocyte;

transmitting, via the at least one monitoring device, the measured sarcomere contraction transients to the user application;

determining, via the user application, the presence of an after-contraction transient for each of the measured sarcomere contraction transients, wherein the after-contraction transient is a secondary peak in a late portion of a relaxation phase of the associated sarcomere contraction transient;

calculating, via the user application, a delta corresponding to a quantity of measured sarcomere contraction transients containing an after-contraction transient;

determining, via the user application, a drug-induced pro-arrhythmia risk in connection with the at least one drug wherein the delta equals or exceeds a pre-determined risk threshold value, said risk threshold value being one percent of the quantity of sarcomere contraction transients in the measured sequence; and

determining, via the user application, a likelihood of an absence of a drug-induced pro-arrhythmia risk in connection with the at least one drug wherein the delta is less than the risk threshold value.

2. The method of claim 1 , wherein the step of determining the at least one drug has taken effect on the at least one cardiomyocyte further comprises the step of determining the at least one drug has reached its plateau effect on the at least one cardiomyocyte.

3. The method of claim 1 , further comprising the step of determining, via the user application, at least one of a peak height, a maximum contraction velocity, a maximum contraction velocity time, a maximum relaxation velocity, a maximum relaxation velocity time, a time to peak, a time to 10% peak, and a time to 50% peak for each of the measured sarcomere contraction transients.

4. The method of claim 1 , wherein the step of measuring, via the at least one monitoring device, a sequence of at least 60 sarcomere contraction transients further comprises the step of measuring a sequence of at least 300 sarcomere contraction transients of the at least one cardiomyocyte.

5. The method of claim 1 , further comprising the step of determining, via the user application, at least one of a peak amplitude, an amplitude height, a time to peak, a rise time, a fall time, a rise slope, a fall slope, a maximum slope, and a minimum slope for each of the measured sarcomere contraction transients.

6. The method of claim 1 , further comprising the step of determining, via the user application, at least one of a time to reaction (“TR”) instability, a TR triangulation, a short-term variability (“STV”) of TR, a TR alternans, a maximum TR dispersion, and an effective refractory period (“ERP”) of TR for the measured sarcomere contraction transients.

7. The method of claim 1 , further comprising the step of determining, via the user application, a number of consecutive sarcomere contraction transients to be measured by the at least one monitoring device and subsequently transmitted to the user application based on at least one of a type of drug being tested, a desired sensitivity of the prediction, and a desired specificity of the prediction.

8. A method for predicting a drug-induced pro-arrhythmia risk in connection with an at least one drug that has been administered to an at least one isolated primary adult cardiomyocyte from a human heart, based on an at least one after-contraction transient (“AC”) associated with the at least one cardiomyocyte, the method comprising the steps of:

implementing an at least one monitoring device positioned and configured for measuring data related to the at least one cardiomyocyte, wherein the at least one monitoring device is an optical device positioned and configured for measuring visual data associated with contractions of the at least one cardiomyocyte;

implementing a user application residing in memory on an at least one computing device, the at least one computing device configured for receiving and processing select data obtained by the at least one monitoring device;

measuring, via the at least one monitoring device, the effect of the at least one drug on the at least one cardiomyocyte;

determining, via the user application, the at least one drug has taken effect on the at least one cardiomyocyte;

applying a controlled external electrical stimulus to the at least one cardiomyocyte;

measuring, via the at least one monitoring device, a sequence of at least 300 sarcomere contraction transients of the at least one cardiomyocyte;

transmitting, via the at least one monitoring device, the measured sarcomere contraction transients to the user application;

determining, via the user application, the presence of an after-contraction transient for each of the measured sarcomere contraction transients, wherein the after-contraction transient is a secondary peak in a late portion of a relaxation phase of the associated sarcomere contraction transient;

calculating, via the user application, a delta corresponding to a quantity of measured sarcomere contraction transients containing an after-contraction transient;

determining, via the user application, a drug-induced pro-arrhythmia risk in connection with the at least one drug wherein the delta equals or exceeds a pre-determined risk threshold value, said risk threshold value being three; and

determining, via the user application, a likelihood of an absence of a drug-induced pro-arrhythmia risk in connection with the at least one drug wherein the delta is less than the risk threshold value.