The prevalence and severity of pests and diseases are factors that limit productivity and quality in commercial cactus pear plantations in Mexico. Recently, in several cactus pear producing regions the appearance of diverse symptoms associated with “heart-shaped cladodes” has been registered. This disease is characterized by the loss of apical dominance of vegetative shoots leading to abnormal cladode growth. Besides the aesthetic damage, vegetative and floral buds disappear in the zone of invagination, thus reducing productivity. Because to date the causal agent is unknown, this study was conducted to analyze three possible agents, damage by insects, physical damage and phytoplasmas that could possibly cause the symptomatology of “heart-shaped cladode”, aiming to constitute a base line for future studies. The study was conducted under semi-controlled conditions and in the field, using Opuntia ficus-indica cv. Villanueva plants and cladodes. To rule out causal agents that occur naturally in cactus pear productive systems, the following characteristics were analyzed: detected presence of Diabrotica undecimpunctata, simulation of physical damage by puncturing 4- and 13-day-old shoots with a needle, and detection of phytoplasmas with PCR and RFLP. The results of the study showed that, although it feeds on shoots, D. undecimpunctata does not cause the symptoms. The puncture with a needle on the apical part promoted the presence of symptoms. The PCR and RFLP analyses detected the presence of phytoplasmas on both symptomatic and asymptomatic shoots. For this reason, it was not possible to conclude that phytoplasmas are the causal agents of heart-shaped cladode.