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These studies suggest that SGLT2 inhibitors and evidence-based therapies can benefit patients with stage 3 heart failure, but individualized treatment is necessary, especially for those with severe kidney disease.
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Patients with stage 3 chronic kidney disease (CKD) are at a significantly increased risk of adverse cardiovascular events, including heart failure. Recent meta-analyses have shown that SGLT2 inhibitors can provide substantial cardiovascular protection for these patients. Specifically, SGLT2 inhibitors have been found to reduce the risk of primary cardiovascular outcomes, such as cardiovascular mortality and hospitalization due to heart failure, by 26% in patients with stage 3/4 CKD. This protective effect is consistent across different stages of CKD and underlying conditions, including type 2 diabetes and heart failure with both preserved and reduced ejection fraction.
Chronic systolic heart failure often coexists with renal insufficiency, particularly stage 3 CKD. Evidence-based therapies, which are typically validated in broader heart failure populations, also show consistent benefits in patients with moderate renal insufficiency. However, data on the efficacy of these therapies in patients with severe renal dysfunction (stage 4 to 5 CKD) are limited. The available evidence suggests that the outcome benefits of these therapies might be even greater in stage 3 CKD compared to those with relatively preserved renal function. Nonetheless, treatment should be individualized, considering the potential risks and benefits, especially in patients with more advanced renal disease.
Subclinical cardiopulmonary dysfunction is common in patients with stage 3 CKD, even in the absence of overt heart failure. Studies have documented reduced exercise capacity, as evidenced by lower peak oxygen consumption (VO2peak), lower anaerobic threshold (AT), and impaired heart rate recovery in these patients. These findings suggest that maladaptive cardiovascular and autonomic dysfunctions are already established in stage 3 CKD, preceding the more severe pathophysiological changes seen in end-stage CKD.
Patients with stage III non-small-cell lung cancer (NSCLC) undergoing high-dose thoracic radiotherapy (RT) are at risk of developing cardiac toxicity, which can include heart failure. Higher heart doses during RT have been associated with worse overall survival and increased incidence of symptomatic cardiac events such as pericardial effusion, acute coronary syndrome, and significant arrhythmias. These cardiac events can occur relatively early, with a median time to the first event of 26 months, underscoring the importance of minimizing heart doses during RT to mitigate these risks.
Stage 3 heart failure, particularly in the context of CKD, presents significant challenges and risks. SGLT2 inhibitors offer promising cardiovascular protection for patients with stage 3 CKD, while evidence-based therapies for systolic heart failure show consistent benefits in those with moderate renal insufficiency. Subclinical cardiopulmonary dysfunction is prevalent in stage 3 CKD, highlighting the need for early intervention. Additionally, cardiac toxicity remains a concern in patients undergoing high-dose RT for stage III NSCLC, necessitating careful management of heart doses to prevent adverse outcomes.
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