Post-hoc analysis of the PARAGON-HF trial to identify the prognostic factors of heart failure patients with preserved ejection fraction

Post-hoc analysis of the PARAGON-HF trial to identify the prognostic factors of heart failure patients with preserved ejection fraction

‌Heart Failure (HF) is a condition where the heart cannot pump blood effectively, leading to fatigue, breathlessness, and fluid buildup. It can be broadly categorized into ‌HF with reduced ejection fraction (HFrEF), ‌HF with mild reduced ejection fraction (HFmrEF), and ‌HF with preserved ejection fraction (HFpEF).‌ In HFpEF patients, the heart's pumping ability (ejection fraction) is normal, but the left ventricle struggles to relax and fill with blood between beats. This results in reduced blood flow to the body despite normal contraction strength. Compared with other types of heart failure, research on HFpEF remains limited. It presents a global health-care challenge. Patients with HFpEF have a normal left ventricular (LV) ejection fraction (LVEF) but experience symptoms and signs of heart failure. Cumulative data suggest that the prognosis for these individuals is comparable to, or even worse than, that of patients with HFrEF. Several factors have been identified as influencing the prognosis of HFpEF, including anemia, diabetes mellitus, chronic kidney disease, and frequent hospital readmissions for heart failure. However, considering the heterogeneity of HFpEF, we speculate that there are still more factors that can affect the prognosis of these patients. Therefore, we plan to re-analyze the data from the PARAGON-HF trial to explore other prognostic factors, especially cardiac structural indicators such as abnormal E/e', global longitudinal strain (GLS), left atrial volume index (LAVi), ‌left ventricular mass index (LVMi), left ventricular wall thickness (LVWT), relative wall thickness (RWT), and tricuspid regurgitation (TR) velocity. Abnormal E/e' Ratio, measured from echocardiography (ultrasound of the heart), can assess left ventricular filling pressures. An elevated E/e' ratio indicates stiffening of the heart muscle, which is common in HFpEF and associated with worse outcomes. GLS evaluates how well the heart muscle fibers shorten during contraction. Reduced GLS is a sensitive marker for early heart dysfunction, even when ejection fraction appears normal. LAVi is used to assess diastolic heart function. Elevated LAVi indicates increased left atrial pressure. LVMi, calculated by dividing left ventricular mass by body surface area, can assess heart muscle thickening. Elevated LVMi, often due to hypertension, signifies increased workload on the heart and is linked to HFpEF risk. Increased LVWT may suggest hypertension or hypertrophic cardiomyopathy. RWT is calculated as (2 × posterior wall thickness)/left ventricular end-diastolic diameter. A value of ≥0.42 indicates concentric hypertrophy, where the heart muscle thickens disproportionately to the chamber size‌. TR Velocity reflects the speed of blood leaking backward through the tricuspid valve. Higher TR velocity indicates elevated right heart pressures, a common complication in advanced HFpEF.The PARAGON-HF trial is a comprehensive study that examined the impact of sacubitril-valsartan compared to valsartan alone on the clinical outcomes of patients diagnosed with HFpEF. In the PARAGON-HF trial, sacubitril/valsartan did not alter the composite primary outcome in HFpEF patients. Subsequent post-hoc analysis indicates that the benefits of sacubitril/valsartan treatment are partially dependent on gender, body mass index (BMI), and concomitant diseases. It is known that HFpEF is a heterogeneous disease. The echocardiographic parameters mentioned above can also be used to classify HFpEF. Therefore, we hypothesize that these echocardiographic parameters may be able to identify subgroups of HFpEF patients who can benefit from sacubitril/valsartan therapy. Then, we intend to re-analyze the data from the PARAGON-HF trial to clarify the prognosis of patients with HFpEF and identify echocardiographic indicators for the benefits of sacubitril/valsartan in HFpEF patients.

[{ "PostingID": 21065, "Title": "NOVARTIS-CLCZ696D2301", "Description": "Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction (PARAGON-HF)" }]