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Cardiovascular (Heart and Blood Vessel) Complications In rare but serious cases, B12 replacement can lead to heart and blood vessel problems: Shortness of breath Peripheral edema (swelling in legs and arms) Rapid weight gain Pulmonary edema (fluid in lungs) Congestive heart failure (heart cannot pump effectively) Blood clots in vessels These complications arise from increased blood volume, thicker blood, and sudden changes in how hard the heart needs to work