Objective: This study aimed to evaluate which voice features can predict health deterioration in patients with chronic HF. Background: Heart failure (HF) is a chronic condition with progressive deterioration and acute decompensations, often requiring hospitalization and imposing substantial healthcare and economic burdens. Current standard-of-care (SoC) home monitoring, such as weight tracking, lacks predictive accuracy and requires high patient engagement. Voice is a promising non-invasive biomarker, though prior studies have mainly focused on acute HF stages. Methods: In a 2-month longitudinal study, 32 patients with HF collected daily voice recordings and SoC measures of weight and blood pressure at home, with biweekly questionnaires for health status. Acoustic analysis generated detailed vowel and speech features. Time-series features were extracted from aggregated lookback windows (e.g., 7 days) to predict next-day health status. Explainable machine learning with nested cross-validation identified top vocal biomarkers, and a case study illustrated model application. Results: A total of 21,863 recordings were analyzed. Acoustic vowel features showed strong correlations with health status. Time-series voice features within the lookback window outperformed corresponding standard care measures, achieving peak sensitivity and specificity of 0.826 and 0.782 versus 0.783 and 0.567 for SoC metrics. Key prognostic voice features identifying deterioration included delayed energy shift, low energy variability, and higher shimmer variability in vowels, along with reduced speaking and articulation rate, lower phonation ratio, decreased voice quality, and increased formant variability in speech. Conclusion: Voice-based monitoring offers a non-invasive approach to detect early health changes in chronic HF, supporting proactive and personalized care.

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