Synchronize Health
Clinical White Paper · 2026

Heart Failure Prevention Protocol

From interoperability to early detection to continuous at-home monitoring — how SYNC-PREVENT™ integrates interoperability-sourced clinical data, advanced biomarker surveillance, Vivio LVEDP screening, and at-home lung-impedance monitoring into a single protocol that detects heart failure before symptoms appear, and intervenes before hospitalization.

JACC Advances 2025;4:102002 · Cantu-Martinez et al.ACC.26 IMPEDANCE-HFPEF Trial · Kleiner-Shochat et al., 2026
Executive Summary

The heart failure detection gap — and how SYNC-PREVENT™ closes it

Heart failure is the most expensive and most preventable catastrophic event in the chronic disease management landscape. It is expensive because it generates repeated hospitalizations, post-acute care, and an escalating pharmacologic burden. It is preventable because the physiologic signals that precede clinical decompensation by days, weeks, or months are now measurable — noninvasively, in the primary care office and in the patient's home.

Two landmark publications — one in JACC Advances in August 2025 and one presented at the ACC.26 Scientific Session in March 2026 — provide direct peer-reviewed evidence for the core clinical tools in the protocol. Together they establish that noninvasive LVEDP screening identifies elevated filling pressure in roughly 40% of high-risk primary care patients, and that lung-impedance-guided outpatient management reduced HF hospitalizations by 81% and all-cause mortality by 60% compared to standard care.

Heart failure does not begin in the emergency department. It begins silently, in the cardiorenal-metabolic milieu, years before the first hospitalization. The protocol that catches it must begin there too.

38.5%
of high-risk primary care patients had elevated LVEDP
Cantu-Martinez et al., JACC Adv. 2025
26.5%
had KCCQ-OS <80 (NYHA Class II–IV) — significant health status impairment
Cantu-Martinez et al., JACC Adv. 2025
81%
reduction in HF hospitalizations with lung-impedance-guided care (74% for first-event)
IMPEDANCE-HFPEF, ACC.26 2026
60%
lower all-cause mortality in the lung-impedance-guided group
IMPEDANCE-HFPEF, ACC.26 2026
AHA Heart Failure Staging

Why SYNC-PREVENT™ begins where standard medicine does not

The 2022 AHA/ACC/HFSA Heart Failure Guideline redefined how heart failure is staged — shifting from a model that begins at symptomatic disease to one that explicitly names the pre-symptomatic phases that precede it. This was not semantic. The guidelines state that patients at Stage A and Stage B should be the primary targets of preventive intervention, not just monitoring. Standard medicine has not yet answered that call at scale. SYNC-PREVENT™ is the infrastructure that does.

Stage A
At Risk for HF

Risk factors present — hypertension, diabetes, obesity, metabolic syndrome, CKD, family history. No structural heart disease. No symptoms.

SYNC-PREVENT™ deploys here: biomarker + device surveillance from age 50, identifying developing risk before structural disease emerges.

Stage B
Pre-HF (Structural / Biomarker)

Structural heart disease, elevated filling pressures, or biomarker evidence (elevated NT-proBNP). No current or prior HF symptoms.

SYNC-PREVENT™ deploys here: Vivio LVEDP screening identifies Stage B patients. 31.4% of Vivio-positive patients in Cantu-Martinez et al. were asymptomatic Stage B.

Stage C
Symptomatic HF

Structural heart disease with current or prior HF symptoms. NYHA Class I–IV. Primary target of pharmacologic and device therapy.

Standard care begins here. At-home lung-impedance monitoring is deployed for confirmed HFpEF — an 81% reduction in hospitalization was demonstrated in the IMPEDANCE-HFPEF trial.

Stage D
Advanced HF

Severe refractory symptoms despite maximal therapy. High mortality. Limited options: transplant or palliative care consideration.

Prevention failed. High-cost interventions, frequent hospitalization, poor prognosis. Stages A and B were the only modifiable window.

Source: Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. Circulation. 2022;145(18):e895–e1032. The 2022 revision introduced Stage A (“at risk”) and Stage B (“pre-HF”) as explicit categories, replacing the older classification that began only at symptomatic disease.

Why SYNC-PREVENT™ begins monitoring at age 50

The intervention window for heart failure prevention opens long before symptoms appear — and closes by the time standard care typically begins. The physiologic changes of Stage A (insulin resistance, hypertension, metabolic syndrome, CKD) begin developing in the fifth decade of life. By age 65, when Medicare monitoring infrastructure is first widely applied, most patients have already accumulated years of Stage A or Stage B pathology.

  1. Age 40–50

    Subclinical cardiometabolic changes begin — insulin resistance, lipid dysregulation, early hypertension. No monitoring. No detection.

  2. Age 50–65

    AHA Stage A risk factors are active; Stage B structural and biomarker changes are developing. The SYNC-PREVENT™ monitoring window opens: Vivio LVEDP screening identifies Stage B patients (38.5% positive rate in this population), biomarker surveillance detects early NT-proBNP elevation, and at-home monitoring is deployed for confirmed HFpEF.

  3. Age 65+

    Medicare enrollment. 70–80% of new enrollees already have 2+ chronic conditions (CMS Chronic Conditions Report). Standard monitoring begins here — typically at Stage C. The Stage A and B window has already closed for most patients.

  4. Age 70+

    First hospitalization. DRG 291/292 claim filed. ACO benchmark breaks. Medicare MLR climbs. The cost of the Stage A/B detection gap arrives — 10–20 years after the window to prevent it closed.

Section I

The clinical evidence base

The protocol is grounded in two independent bodies of peer-reviewed evidence published in 2025 and 2026. Both directly evaluate the specific tools deployed in the protocol and provide quantified outcomes that form its clinical and financial justification.

Evidence Source 1 — Vivio System LVEDP Screening

Cantu-Martinez O, Girard AA, Jin W, et al. Noninvasive Screening for Elevated LVEDP and Health Status in Outpatients at Risk for Heart Failure. JACC Adv. 2025;4:102002.

JACC Advances, Vol. 4, No. 8, August 2025. Open access (CC BY). Conducted at 3 primary care clinics, funded in part by NHLBI.

Study design
A cross-sectional convenience sample of 2,040 adults screened at 3 primary care clinics between August and November 2024 — patients with diabetes, CKD Stage 3+, or a physician's clinical suspicion of HF. Patients with a known HF diagnosis were excluded. The Vivio System screened for estimated LVEDP >18 mm Hg.
Key finding 1
Among 2,040 screened patients (mean age 74 ± 8; 49.8% women; 64.6% with diabetes; 34.9% with CKD), 38.5% had an estimated elevated LVEDP. Older patients, women, and those with CKD were significantly more likely to have elevated LVEDP (P < 0.01 for all).
Key finding 2
Of 653 patients with elevated LVEDP who completed the KCCQ-12, 31.4% were asymptomatic (AHA/ACC Stage B, pre-HF), while 26.5% had KCCQ-OS scores below 80, consistent with NYHA Class II–IV. Over two-thirds of patients with elevated LVEDP had meaningful health status impairment at the time of first detection.
Device specifications
The Vivio System is 510(k) FDA-cleared. It uses a modified pneumatic brachial blood-pressure cuff synchronized with a single-lead ECG to collect 40 seconds of brachial pulse waveform and ECG data. Estimated elevated LVEDP (>18 mm Hg) is identified with reported sensitivity of 80% and specificity of 83%.
Clinical implication
At a 38.5% positive screening rate, a 1,000-patient panel is expected to identify roughly 385 patients with elevated LVEDP. About 30% (≈115) will be asymptomatic Stage B — patients for whom early intervention can prevent progression — and 100+ more will have NYHA Class II–IV symptoms requiring immediate attention. These are patients whose standard care is currently missing them.
Evidence Source 2 — At-Home Lung-Impedance Monitoring

Kleiner-Shochat M, et al. IMPEDANCE-HFPEF: Early Noninvasive Detection of Lung Fluid Reduces Death, Hospitalization. Presented at ACC.26, March 2026.

American College of Cardiology Annual Scientific Session 2026. Single-center, single-masked RCT. 150 patients with HFpEF. Median follow-up 38.4 months. Device: CardioSet Edema Guard Monitor.

Study design
150 patients with HFpEF (mean age ~75, 62% women, LVEF ~60%) randomized 1:1 to lung-impedance-guided care vs. standard care. The monitor measured pulmonary congestion at each outpatient visit; the intervention group's clinicians adjusted medications per protocol. Clinic visit counts were equal between groups.
Regulatory status
The CardioSet Edema Guard Monitor's current FDA clearance (2025) is for HFrEF. The IMPEDANCE-HFPEF trial evaluated it in an HFpEF population; deployment for HFpEF monitoring in this protocol is therefore based on this published clinical evidence rather than the device's currently cleared indication, and should be reviewed in light of the treating physician's clinical judgment.
Primary endpoint
Recurrent HF hospitalization at 38.4-month median follow-up. The lung-impedance-guided group had a substantial reduction in HF hospitalizations versus standard care — time to first HF hospitalization was 602 days vs. 83 days.
Secondary endpoints
60% lower all-cause mortality and 74% lower HF-specific mortality in the lung-impedance-guided group. No device-related adverse events.
Mechanism
Clinicians in the lung-impedance group adjusted medications more than twice as often, and earlier — at the preclinical stage of lung congestion, when response to treatment is most powerful. That earlier intervention prevented the fluid-accumulation cascade that drives HF hospitalization.
Clinical implication
For a 1,000-patient panel with ~385 patients screening positive for elevated LVEDP, at-home monitoring for confirmed HFpEF could reduce HF hospitalizations by 74% (first-event) to 81% (recurrent, the trial's full primary endpoint) in that subpopulation. At an average Medicare HF hospitalization cost of $14,000+, preventing even 10 hospitalizations a year represents $140,000 in medical cost avoidance — before mortality reduction.
Section II

The interoperability foundation — clinical data before the patient arrives

The protocol begins before the first device is deployed. The SYNC-PREVENT™ interoperability layer — built on Carequality and TEFCA connectivity — ingests multi-source clinical data to identify HF risk and prioritize who should receive Vivio screening and downstream monitoring. This data arrives from sources the ordering physician may never see in a standard encounter.

Data SourceWhat SYNC-PREVENT™ ingestsHF risk signal identified
Hospital ADT feedAdmissions, discharges, transfers via TEFCARecent HF admission, HF-related ED visit, diuretic administration during admission
Reference laboratoryNT-proBNP, hs-Troponin from Quest / LabCorpNT-proBNP elevation, rising troponin trend, BNP above age-adjusted threshold
Pharmacy networkActive medication list including cardiology prescriptionsLoop diuretic, SGLT-2 inhibitor, MRA, ARNI — all HF therapy markers
Specialist notesCardiology, nephrology, endocrinology visit summariesPrior echocardiogram findings, diastolic dysfunction notation, CKD staging
Imaging summariesRadiology and echocardiogram reportsLVEF, LA enlargement, E/e' ratio, pulmonary vascular congestion on chest X-ray
Primary care EMRProblem list, vital trends, recent labsHypertension, diabetes, CKD — the exact comorbidity triad from Cantu-Martinez et al.

The layer applies the exact eligibility criteria validated in Cantu-Martinez et al.: diabetes, CKD Stage 3+, or physician clinical suspicion of HF. Every enrolled patient meeting one or more is automatically flagged for Vivio screening — protocol-driven, triggered by interoperability data, and routed to the clinical team, not dependent on the physician recalling it at the point of care.

Section III

Four steps from risk identification to continuous monitoring

The protocol operates as a sequential, evidence-based pathway. Each step is triggered by the preceding step's findings, so the most intensive monitoring resources reach the patients who need them most.

Step 1
Interoperability risk identification
What happens
The system continuously queries the Carequality/TEFCA network for enrolled patients and ingests ADT feeds, lab results, medication lists, and specialist notes. Patients matching the Cantu-Martinez et al. eligibility criteria are automatically flagged for Vivio screening.
Triggering signals
NT-proBNP above age-adjusted threshold · rising hs-Troponin trend · loop diuretic in active medications · CKD Stage 3+ · diabetes · prior HF-related hospitalization · echocardiogram showing diastolic dysfunction.
Expected yield
In a 1,000-patient panel with 64.6% diabetes and 34.9% CKD prevalence (per the study population), roughly 700–800 patients will meet one or more Vivio screening criteria.
Step 2
Advanced biomarker assessment
What happens
Physician-ordered Layer 1–4 biomarker testing provides the cardiometabolic context for interpreting the Vivio result, arriving before or alongside the assessment so the physician understands the full metabolic environment driving the hemodynamic finding.
HF-relevant biomarkers
NT-proBNP and hs-Troponin (cardiac stress and injury) · Cystatin-C / ACR (cardiorenal coupling) · ApoB / GlycA (atherogenic burden) · HbA1c / LP-IR (metabolic drivers of HFpEF) · FIB-4 / Ferritin / TSAT (hepatic-cardiometabolic interconnection).
Clinical significance
The study found CKD patients significantly more likely to have elevated LVEDP (38.3% vs 32.7%, P=0.010). Cystatin-C and ACR detect renal impairment earlier than creatinine-based eGFR, identifying the cardiorenal patients most likely to screen positive before the Vivio screen is performed.
Step 3
Vivio LVEDP screening — early confirmation
What happens
A Synchronize Health technician deploys the Vivio System in the physician's office. The 40-second brachial-cuff/ECG assessment returns an estimated LVEDP, categorized as elevated (>18 mm Hg) or normal, routed to the ordering physician in real time — with a KCCQ-12 health-status assessment for elevated results.
Evidence basis
Cantu-Martinez et al. (JACC Adv. 2025;4:102002) demonstrated a 38.5% positive rate in a primary care population with diabetes, CKD, or suspected HF; sensitivity 80%, specificity 83% for LVEDP >18 mm Hg. It is the first study to characterize patients' health status at the time of potential HF recognition — establishing this as a clinically significant detection event, not an incidental finding.
Expected yield
In a 1,000-patient panel: ~385 positive screens — of which ~115 asymptomatic Stage B (pre-HF) for early intervention, ~162 with NYHA Class I, ~55 with Class II, and ~47 with Class III/IV requiring urgent evaluation.
Step 4
At-home lung-impedance monitoring — continuous surveillance
What happens
Patients with confirmed elevated LVEDP and an HFpEF diagnosis are enrolled in at-home lung-impedance monitoring with the CardioSet Edema Guard, which measures pulmonary congestion between visits by isolating the lung signal from chest-wall noise. Clinicians get early warning of fluid accumulation — days to weeks before symptoms — enabling medication adjustment at the preclinical stage.
Evidence basis
The IMPEDANCE-HFPEF trial (ACC.26, March 2026) in 150 HFpEF patients over 38.4 months: 81% reduction in recurrent HF hospitalizations (74% in first-event hospitalizations), time to first hospitalization 602 vs. 83 days, 60% lower all-cause mortality, 74% lower HF-specific mortality, and zero device-related adverse events.
Expected yield
Applying a conservative 74% hospitalization reduction (the trial's full primary endpoint demonstrated 81%) to the ~385 Vivio-positive patients, monitoring could prevent roughly 43 hospitalizations a year per 1,000 enrolled — around $600,000 in medical cost avoidance at $14,000 per Medicare HF hospitalization.
Section IV

Protocol summary — interoperability to at-home monitoring

StepTool / methodExpected yieldEvidence source
1 · Interoperability risk IDCarequality / TEFCA — ADT, labs, medications, specialist notes~700–800 / 1,000 flagged for Vivio screening (DM + CKD criteria)Cantu-Martinez et al. eligibility criteria
2 · Biomarker assessmentLayer 1–4 panel — NT-proBNP, hs-Troponin, Cystatin-C, ApoB, LP-IR, HbA1c, FIB-4Cardiorenal risk context delivered before the Vivio resultSYNC-PREVENT™ 11-layer architecture
3 · Vivio LVEDP screeningVentric Health Vivio System — 510(k) FDA-cleared brachial cuff / ECG~385 / 1,000 positive (38.5%): ~115 asymptomatic Stage B, ~260 symptomatic NYHA I–IVCantu-Martinez et al. JACC Adv. 2025;4:102002
4 · At-home monitoringCardioSet Edema Guard — at-home lung impedance81% reduction in recurrent HF hospitalizations (74% first-event), 60% reduction in all-cause mortalityIMPEDANCE-HFPEF, ACC.26 March 2026
Section V

Per-1,000-patient savings model

This model applies published trial yield figures directly to a 1,000-patient panel. Every number is based on peer-reviewed evidence — the 38.5% Vivio positive rate (Cantu-Martinez et al.) and a conservative 74% hospitalization reduction applied from IMPEDANCE-HFPEF (whose full primary endpoint demonstrated 81%). Assumptions are stated explicitly and are conservative.

  1. 1,000
    Total enrolled patients

    Base panel — 50 / 30 / 20 Stable / Moderate / Complex tier distribution

    100%
  2. ~700–800
    Meet Vivio screening criteria

    Diabetes, CKD Stage 3+, or physician suspicion — Cantu-Martinez et al. criteria applied via the interoperability feed

    70–80%
  3. ~385
    Vivio-positive (elevated LVEDP)

    38.5% positive rate — Cantu-Martinez et al., JACC Adv. 2025. Sensitivity 80%, specificity 83%

    38.5%
  4. ~115
    Asymptomatic Stage B (pre-HF)

    31.4% of Vivio-positive — AHA/ACC Stage B, no HF symptoms. Highest-value target; disease still reversible

    31.4% of positive
  5. ~150–200
    HFpEF confirmed — at-home monitoring deployed

    Conservative estimate from the Vivio-positive pool. Outpatient medication adjustment guided by lung-impedance readings

    ~40% of positive
  6. ~19–30
    HF hospitalizations prevented annually

    Conservative 74% reduction (trial's full primary endpoint 81%) — IMPEDANCE-HFPEF, ACC.26 2026 — applied to 25–40 expected annual hospitalizations in the unmonitored HFpEF population

    74% reduction
Category 1
HF hospitalization avoidance
$266K–$420K

19–30 prevented hospitalizations × $14,000+ avg Medicare cost

IMPEDANCE-HFPEF (ACC.26 2026) · 74% reduction applied (conservative; primary endpoint 81%)

Category 2
30-day readmission avoidance
$76K–$150K

~19–30 prevented readmissions × $4,000–$5,000 avg 30-day readmission cost

CMS HF 30-day readmission penalty program

Category 3
ACO shared savings & Star rating value
$200K–$400K+

MSSP shared savings at 50–75% share rate; MA Star Rating quality bonus protection

HF readmission rate — MSSP quality measure

Total estimated annual financial impact · 1,000-patient panel
$542,000 – $970,000+

Conservative range · hospitalization avoidance + readmission avoidance + ACO/Star value, per 1,000-patient panel annually

Per patient per year: $542–$970SYNC-PREVENT™ monitoring cost: $49.58 / patient / month ($595 / patient / year)

The projections apply published evidence to conservative population assumptions. Actual results will vary with panel composition, CKD and diabetes prevalence, physician response rates to alerts, and symptom burden at enrollment.

Methodology: a conservative 74% hospitalization reduction (the IMPEDANCE-HFPEF full primary endpoint demonstrated 81%) is applied to the expected Vivio-positive population from Cantu-Martinez et al. (38.5%). These are evidence-based estimates, not guarantees.

Section VI

Why the published evidence directly applies

A common limitation of applying trial evidence to a clinical program is population mismatch. Here, the alignment between the published study populations and the SYNC-PREVENT™ enrolled population is exceptional.

Population variablePublished studiesSYNC-PREVENT™ target population
Mean age74 ± 8 (Cantu-Martinez) · ~75 (IMPEDANCE)50–64 (pre-Medicare) + 65+ (Medicare) — overlapping cohort
Sex distribution49.8–62% womenConsistent with the general Medicare population
Diabetes prevalence64.6% in Cantu-Martinez et al.40% planning assumption — conservative; rural Medicare may exceed 50%
CKD prevalence34.9% in Cantu-Martinez et al.Consistent with the Layer 2 monitoring trigger population
SettingPrimary care outpatient clinicsOperates inside physicians' primary care and specialty clinics
HFpEF (IMPEDANCE trial)LVEF ~60%, mean age ~75, 62% womenHFpEF is the dominant HF subtype in the Medicare 65+ population
No prior HF diagnosisExclusion criterion in Cantu-MartinezTargets pre-diagnosis monitoring — identical population definition

The populations are similar enough that the published yield figures — 38.5% LVEDP elevation, 26.5% NYHA Class II–IV symptom burden, and 81% hospitalization reduction — are the most clinically defensible estimates available for projecting this program's impact. Nearly 40% of high-risk primary care patients have elevated filling pressure today. Over 80% of the hospitalizations they will generate are preventable. The evidence is peer-reviewed. The tools are FDA-cleared. The protocol is operating.

References
  1. Cantu-Martinez O, Girard AA, Jin W, Rinderknecht D, Cheek T, Spertus JA. Noninvasive Screening for Elevated LVEDP and Health Status in Outpatients at Risk for Heart Failure. JACC Adv. 2025;4(8):102002. Open access CC BY.
  2. Kleiner-Shochat M, et al. IMPEDANCE-HFPEF: Early Noninvasive Detection of Lung Fluid Reduces Death, Hospitalization. Presented at ACC.26, American College of Cardiology Annual Scientific Session; March 29–31, 2026.
  3. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. Circulation. 2022;145(18):e895–e1032.
  4. Bozkurt B, Ahmad T, Alexander KM, et al. Heart Failure Epidemiology and Outcomes Statistics: A Report of the Heart Failure Society of America. J Card Fail. 2023;29(10):1412–1451.
  5. Ndumele CE, Rangaswami J, Chow SL, et al. Cardiovascular-Kidney-Metabolic Health: A Presidential Advisory From the American Heart Association. Circulation. 2023;148(20):1606–1635.
  6. Virani SS, et al. Heart Disease and Stroke Statistics — 2022 Update. J Am Coll Cardiol. 2022;80(6):565–578.

This white paper applies peer-reviewed clinical evidence to modeled population assumptions for illustration; figures are evidence-based estimates, not guarantees, and actual results vary by population. The CardioSet Edema Guard Monitor is FDA-cleared for HFrEF; its use for HFpEF monitoring reflects the IMPEDANCE-HFPEF trial evidence rather than its cleared indication and remains subject to the treating physician's clinical judgment. The treating physician retains full authority over every clinical decision.

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