### Voice and Speech as Biomarkers of Health  
Characterizing voice and speech characteristics provides an accessible, non-invasive way to monitor physiological changes throughout the body, both for voice disorders and as a biomarker of general health [16; 17]. Especially in recent years, voice and speech biomarkers have been developed to monitor several laryngeal, neurological, and psychological disorders. These include vocal hyperfunction [18], depression [19], Parkinson's disease [20; 21], and amyotrophic lateral sclerosis [22]. Voice has also been increasingly used as a biomarker for cardiovascular and respiratory disorders, including coronary artery disease [23], pulmonary hypertension [24], and COVID-19 [25].  
[PERSON] et al. [26] developed a vocal biomarker that predicted hospitalization and mortality in patients with HF. The biomarker was developed from a cohort of over 8000 speakers with chronic conditions other than HF, including cancer, lung disease, and diabetes. Acoustic voice features relating to the cepstrum, pitch, loudness, and perturbation were extracted from 20 s voice samples. A large set of abstract, high-level features was extracted from the time series of these acoustic features, and the resulting data set was used to train a linear biomarker model to predict all-cause mortality. When tested on a separate cohort of 2200 speakers with HF, the biomarker was associated with the risk of both hospitalization and mortality. Each increase of one standard deviation in the biomarker represented an increase in risk of 48% for death and 25% for hospitalization during the 20-month follow-up period. This study strongly suggests that the pathophysiology of HF causes clinically relevant changes in the voice, although the specific mechanisms that governed the relationship between voice and HF status were not investigated and are still unknown. [PERSON] et al. did not identify specific voice features that were well-correlated with the risk of hospitalization or mortality. However, in that and related work [24], changes in laryngeal perfusion, impaired vagus nerve functioning, physical compression of the left recurrent laryngeal nerve, and increased emotional distress are implicated as possible causes of voice changes due to cardiopulmonary disease.  
In a recent study, five speech measures were analyzed from 40 patients with ADHF at admission and discharge [27]. The specific acoustic measures were not reported but showed good accuracy in distinguishing voice samples from admission versus discharge. In a particularly novel contribution, [PERSON] et al. [27] included an auditory-perceptual evaluation in which 20 listeners classified seven voice samples from each of three patients with ADHF as either \"wet\" (having increased fluid levels on admission) or \"dry\" (having fluid levels return to baseline at discharge). Listeners were able to correctly classify these samples in 67% of cases, which was statistically above the 50% chance rate. These results, albeit very preliminary due to a small sample size, indicate that voice changes in heart failure may be significant enough to be detected perceptually as well as acoustically, which is the focus of the current line of research.  
Figure 1: Hypothesized effects of HF-related congestion on laryngeal edema, voice airflow, and properties of the acoustic voice signal, whose features have the potential to be detectable earlier than systemic increases in body weight.