The genetic basis of congenital heart disease is yet to be defined, and the interactions between the malformed heart and biomechanical cardiac performance remain poorly understood. Functional optical imaging enables detailed biomechanical phenotyping of cardiac dysfunction in small animal models, which in turn enables specific gene-phenotype relationship. We have developed a new microangiography technique based on flow imaging using endogenous hemoglobin contrast enabling in vivo assessment and biomechanical phenotyping of Xenopus tropicalis embryonic heart. We demonstrated that hemoglobin contrast angiography can be used to quantify physiological response to treatment with well-established cardioactive drugs.