Abstract

CARDIAC HYPERTROPHY: INSIGHTS INTO PATHOPHYSIOLOGY, BIOMARKERS, AND PRECISION TREATMENT APPROACHES

Pranita Yengunde*, Prof. Shailesh Patwekar, Yuvraj Navkhande, Abhinav Bhadange, Tejaswini Usrate

ABSTRACT

Cardiac hypertrophy is a complex structural and functional adaptation of the heart in response to sustained hemodynamic overload and neurohormonal stimulation. While physiological hypertrophy, such as that induced by regular endurance training, is typically adaptive and reversible, pathological hypertrophy due to chronic conditions like hypertension, valvular heart disease, or genetic cardiomyopathies is maladaptive and often leads to progressive cardiac remodeling, fibrosis, arrhythmogenesis, and ultimately heart failure. Understanding the intricate molecular and cellular mechanisms driving hypertrophic growth is crucial for developing targeted therapies and improving patient outcomes. Numerous signaling pathways have been identified as key regulators of cardiac hypertrophy. Among these, the MAPK pathway (including ERK1/2, JNK, and p38) plays a pivotal role in cellular growth and stress responses. The PI3K/Akt pathway predominantly mediates physiological hypertrophy and promotes cardiomyocyte survival, whereas the calcineurin–NFAT pathway is central to pathological gene reprogramming. Additional modulators such as G-protein–coupled receptors, TGF-β signaling, and the mTOR pathway further orchestrate the balance between adaptive and maladaptive remodeling. Neurohormonal factors like the renin–angiotensin–aldosterone system (RAAS), endothelin-1, and catecholamines exacerbate pathological hypertrophy through sustained stimulation. Advances in diagnostic approaches have enhanced early detection and monitoring. Non-invasive imaging techniques, including echocardiography and cardiac MRI, remain gold standards for assessing structural changes. Electrocardiography aids in screening, while histopathology provides mechanistic insights in research. A growing array of biomarkers, such as BNP, NT-proBNP, cardiac troponins, CRP, galectin-3, ST2, and microRNAs, hold promise for precision diagnosis and prognosis. Therapeutic strategies encompass established pharmacological treatments like ACE inhibitors, ARBs, beta-blockers, and diuretics, alongside emerging targets such as GPR35 modulators, microRNA therapies, and antifibrotic agents. Lifestyle modification and regular exercise remain vital non-pharmacological interventions. Future research should focus on translating molecular insights into novel, biomarker-guided therapies to halt or reverse pathological remodeling, thereby reducing the burden of heart failure related to cardiac hypertrophy.

Keywords: Cardiac hypertrophy; signaling pathways; biomarkers; left ventricular hypertrophy; heart failure; molecular mechanisms.