Introduction Transthyretin cardiac amyloidosis (ATTR-CA) is a rare but increasingly recognized cause of heart failure, characterized by misfolded transthyretin protein deposition in the myocardium. We present a 60-year-old man admitted to the Cardiology Department with heart failure exacerbation and multiple comorbidities. Case report Upon admission, the patient exhibited dyspnea, right ventricular heart failure with massive edema, chronic kidney disease, cachexia, and weakness. His medical history included chronic obstructive pulmonary disease, hypertension, dyslipidemia, and atypical pulmonary alveolitis, with elevated NT-proBNP and troponin levels detected. Electrocardiogram (ECG) showed low QRS voltages and residual R waves in V1-V3. Transthoracic echocardiography revealed concentric myocardial hypertrophy, hyperechogenic left ventricle (LV) muscle irregularly saturated, hypokinesis of the inferoseptal segment, characteristic non-specific striations and severe diastolic dysfunction of the mitral valve. Serum protein immunofixation detected a polyclonal distribution of heavy and light chains, raising suspicion of cardiac amyloidosis. A positron emission tomography (PET) scan confirmed tracer uptake and typical changes consistent with ATTR-CA, confirming the initial diagnosis. The wild-type form of ATTR amyloidosis was ruled out with genetic testing. The patient was prescribed empagliflozin, torasemide, acetylsalicylic acid, and omeprazole, pending tafamidis treatment approval from the bioethics committee. Conclusions This case highlights the challenging diagnostic journey in a patient presenting with heart failure exacerbation and a complex clinical profile. Management of ATTR-CA involves a multidisciplinary approach, including optimization of heart failure medications and consideration of emerging therapies such as tafamidis. In this case, the patient was prescribed standard heart failure medications pending approval for tafamidis treatment from the bioethics committee. Early recognition and accurate diagnosis are essential for initiating appropriate treatment strategies and improving patient outcomes.