Comment on: The Perfusion Index May Be an Accurate Tool for Predicting the Progression of Ischemia in Patients With Peripheral Arterial Disease

To the Editor,

We read with great interest the recent article by Komai et al ¹ investigating the clinical utility of the Perfusion Index (PI) for predicting the progression of ischemia in patients with peripheral arterial disease (PAD). We commend the authors for seeking a rapid, non-invasive bedside tool to risk-stratify claudicants. However, a critical appraisal of their methodology raises several questions regarding the true clinical utility and reliability of PI, particularly in the demographics most at risk for developing chronic limb-threatening ischemia (CLTI).

First, the authors explicitly state in their introduction that the conventional ankle-brachial index (ABI) is frequently unreliable in patients with diabetes or chronic kidney disease due to medial arterial calcification. Indeed, recent literature heavily emphasizes that medial artery calcification is an independent and primary driver of amputation and poor limb-related outcomes. ² Paradoxically, however, the authors actively excluded patients with an ABI ≥1.3 as well as those with existing diabetic foot lesions. By intentionally eliminating the exact cohort where ABI fails and where non-compressible vessels complicate diagnosis, how can the authors claim that PI solves this specific unmet clinical need? A diagnostic marker that only demonstrates validity in compressible, non-diabetic vessels offers little incremental value over current American and European consensus guidelines, which prioritize alternative microvascular assessments precisely when the ABI is confounded.^3,4

Second, the correlation reported between the average PI (PIave) and skin perfusion pressure (SPP) is alarmingly weak. The authors celebrate a “significant” positive correlation of r = .215 (P < .001). While it may reach statistical significance due to the large sample size, clinically, an r-value of .215 indicates that PI explains <5% (R² = .046) of the variance in SPP. SPP is a highly reliable metric that evaluates true capillary microcirculation and tissue viability. ⁵ Given this extremely poor agreement, it is highly questionable whether PI is capturing the same physiological endpoint as SPP, or if it is merely recording a proximal pulsatile signal that fails to translate into actual tissue-level perfusion. ⁶ Can a tool with such a low correlation to established microcirculatory gold standards safely replace them to guide decisions between conservative and invasive management?

Third, the follow-up duration of merely 3 months for asymptomatic patients and those with claudication is notably insufficient. PAD is inherently a chronic, progressive condition. Contemporary international guidelines strongly underscore the necessity of long-term surveillance to accurately capture major adverse limb events (MALE).^3,4 The authors report an impressive 98% negative predictive value for CLTI progression within this narrow window. However, what is the predictive power of a PIave ≥0.27 at 12 or 24 months? Reassuring a patient and a physician based on a 3-month horizon lacks longitudinal rigor and may inadvertently lead to delayed interventions and catastrophic tissue loss in the long run.

Finally, PI is derived from a pulse oximeter signal heavily influenced by peripheral vasomotor tone, which fluctuates wildly with sympathetic arousal, pain, hydration status, and anxiety. ⁷ While the authors appropriately controlled the ambient room temperature (20-25°C), they did not (and could not) account for the endogenous sympathetic tone of the subjects. This inherent physiological variability could easily mask true ischemic progression, a limitation that undermines its reliability as a consistent outpatient screening tool.

In summary, while PI represents an attractive, low-cost concept for evaluating toe ischemia, its current validation in this study is severely hindered by the paradoxical exclusion of high-risk calcified patients, an extremely weak physiological correlation with established microcirculatory markers (SPP), and a short follow-up period. Before PI can be safely adopted as a reliable gatekeeper for conservative therapy versus revascularization in PAD, future studies must specifically include diabetic populations with medial arterial calcification, directly compare PI against long-term (1-2 years) clinical limb salvage rates, and address the vast individual variability in peripheral vasomotor tone.