Kardiyak Amiloidoz
Özet
Kardiyak amiloidoz, hatalı katlanmış proteinlerin miyokartta hücre dışı alanda birikerek ventrikül duvarlarında kalınlaşmaya, sertlik artışına ve restriktif tipte diyastolik disfonksiyona yol açtığı progresif ve ölümcül bir hastalıktır. Günlük pratikte tanı konulan vakaların %98'den fazlasını immunglobulin hafif zincir (AL) ve transtretin (ATTR) amiloidoz tipleri oluşturmaktadır. AL amiloidoz, kemik iliğindeki klonal plazma hücrelerinden köken alan monoklonal hafif zincirlerin birikimiyle seyreder ve oldukça agresif bir klinik seyir gösterir. ATTR amiloidoz ise TTR genindeki mutasyonlara bağlı gelişen herediter (ATTRv) veya yaşlanma süreciyle ortaya çıkan vahşi tip (ATTRwt) olmak üzere ikiye ayrılır. Hastalar sıklıkla pulmoner konjesyon semptomları ve korunmuş ejeksiyon fraksiyonlu kalp yetmezliği tablosuyla başvururlar. Tanısal süreçte EKG'de düşük voltaj, ekokardiyografi ve kardiyak MRI'da ventrikül hipertrofisi ve küresel longitudinal strainde azalma gibi "ikaz işaretleri" kritik rol oynar. Kesin tanı, hematolojik taramalar, 99mTc-fosfonat sintigrafisi, biyopsi ve genetik analiz kombine edilerek konulur. Tedavi yönetimi, diüretiklerle semptomların hafifletilmesini ve hastalıktan sorumlu protein üretimi ile agregasyonunu hedefleyen daratumumab (AL için) veya tafamidis (ATTR için) gibi spesifik ajanların kullanımını içerir.
Cardiac amyloidosis is a progressive and fatal disease characterized by the extracellular deposition of misfolded proteins in the myocardium, leading to ventricular wall thickening, increased stiffness, and restrictive diastolic dysfunction. In clinical practice, more than 98% of diagnosed cases are comprised of monoclonal immunoglobulin light chain (AL) and transthyretin (ATTR) amyloidosis types. AL amyloidosis is driven by the accumulation of monoclonal light chains originating from clonal plasma cells in the bone marrow and exhibits a highly aggressive clinical course. ATTR amyloidosis is categorized into the hereditary form (ATTRv), caused by mutations in the TTR gene, and the wild-type form (ATTRwt), which develops secondary to aging. Patients commonly present with pulmonary congestion symptoms and heart failure with preserved ejection fraction. In the diagnostic process, "red flags" such as low voltage on ECG, ventricular hypertrophy on echocardiography and cardiac MRI, and reduced global longitudinal strain play a crucial role. Definitive diagnosis is established by combining hematological screening, 99mTc-phosphonate scintigraphy, biopsy, and genetic analysis. Management includes alleviating symptoms with diuretics and utilizing disease-specific agents like daratumumab (for AL) or tafamidis (for ATTR) that target responsible protein production and aggregation.
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