Outpatient clinic visits before and after hospitalizations for heart failure with and without transthyretin amyloid cardiomyopathy

Transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly recognized cause of heart failure (HF).1,2 Outpatient clinic visits are an important opportunity to optimize guideline-directed medical therapy for the general HF population, as well as specific disease-modifying medications for those with ATTR-CM. Yet, large-scale data detailing the type and frequency of outpatient clinic visits for patients with HF are limited, and the degree to which longitudinal outpatient follow-up may differ for patients with HF with and without ATTR-CM is unclear. In this context, we leveraged the Get With The Guidelines-Heart Failure registry linked to administrative claims to examine the frequency and type of outpatient clinic visits before and after a HF hospitalization, including among patients with and without comorbid ATTR-CM. We examined US patients hospitalized for HF in the American Heart Association’s Get With The Guidelines—Heart Failure (GWTG-HF) registry between 1 January 2021 and 30 June 2024. All patients were aged ≥65 years and linked to Medicare fee-for-service claims data (inpatient, outpatient, and carrier files) using a validated approach.3 For patients with multiple HF hospitalizations during the study period, the first hospitalization was used as the index. Patients missing data regarding ATTR-CM status or ejection fraction were excluded. Patients who left the index hospitalization against medical advice, were discharged to hospice or another palliative care setting, or to another facility, were excluded, as were patients who died during the index hospitalization. In-person outpatient clinic visits were examined during the 6 months before and after the index HF hospitalization. Outpatient clinic visits were defined by Medicare outpatient and carrier files using current procedural terminology (CPT) and healthcare common procedure coding system (HCPCS) codes (99201–99205, 99212–99215, G2211), with restriction to relevant revenue center and place of service codes. The specialty type for each outpatient clinic visit was defined by Medicare specialty codes and categorized as cardiology, neurology, primary care, or internal medicine, or other. Visits involving clinicians or staff deemed unlikely to modify patient medical therapy were excluded (e.g. physical or occupational therapy, dental visits, diagnostic radiology, clinical laboratory, social work visits, medical supply/equipment visits). The proportion of patients with ≥1 outpatient visit, median (25th, 75th) number of visits, and specialty type (cardiology, neurology, primary care, etc.) of outpatient visits were compared among patients with HF with versus without ATTR-CM. Pearson chi-square tests were used for categorical variables and Wilcoxon rank-sum tests for continuous variables. ATTR-CM was defined by the GWTG-HF registry case report and reflects data abstracted from clinical documentation. All statistical analyses were performed by the Duke Clinical Research Institute (Durham, NC, USA), utilizing SAS Software, version 9.4 (SAS Institute Inc., Cary, NC, USA). P < .05 was considered statistically significant. Across 592 US sites, the study included 229 patients with HF with ATTR-CM and 112 641 with HF without ATTR-CM. Of those with ATTR-CM, 68 (29.7%) were diagnosed prior to index hospitalization, 57 (24.9%) during index hospitalization, and 104 (45.4%) were missing data on the time of diagnosis. Median (25th–75th) age was similar between patients with and without ATTR-CM (82 [76–87] vs 81 [74–87] years, P = .08), but patients with ATTR-CM were less likely to be female (30% vs 53%, P < .001). Patients with ATTR-CM had a lower median ejection fraction (45% [32–57] vs 53% [37–60]), were less likely to have diabetes (28% vs 43%), chronic obstructive pulmonary disease (22% vs 31%) and hypertension (83% vs 88%), and more likely to have a history of atrial fibrillation/flutter (65.5% vs 52.6%) (all P < .03). At time of index admission, patients with ATTR-CM had a lower median systolic blood pressure (124 [111–145] vs 140 [122–160] mmHg), estimated glomerular filtration rate (41 [30–58] vs 51 [34–71] mL/min/1.73 m2), and body mass index (26.8 [23.6–30.1] vs 28.6 [24.4–34.2] kg/m2) (all P < .001). At discharge, patients with ATTR-CM were more likely to be prescribed a SGLT2i (24% vs 14%) and MRA (31% vs 21%), and less likely to be prescribed beta-blockers (51% vs 77%) and ACEI/ARB/ARNI (27% vs 44%) (all P < .001). Among all 112 870 patients, 102 888 (91%) had ≥1 outpatient visit of any kind in the 6 months before hospitalization, and 98 149 (87%) patients had ≥1 outpatient visit of any kind in the 6 months after hospitalization. The median number of outpatient visits of any kind in the 6 months before HF hospitalization was 5 (3–9) visits, and the median in the 6 months after HF hospitalization was 6 (2–9) visits. Compared with HF without ATTR-CM, those with ATTR-CM were more likely to have ≥1 visit (97% vs 91%, P = .02) and had a higher median number of outpatient visits (7 [5–12] vs 5 [3–9], P < .001) in the 6 months preceding hospitalization. A similar pattern persisted in the six months after index hospitalization (Figure 1). Frequency and type of outpatient clinic visits 6 months before and after HF hospitalization Regarding the type of outpatient visits, 6 months before and after HF hospitalization, most patients (both with and without ATTR-CM) were seen by cardiology (51.3% before and 59.3% after) and primary care (63.1% before and 56.4% after). The greatest proportion of patients had clinic visits with other types of clinicians (78.7% before and 75.8% after). Compared with HF without ATTR-CM, patients with ATTR-CM were more likely to be seen in the cardiology clinic before HF hospitalization, and trended towards being more likely to be seen in the cardiology clinic after HF hospitalization (Figure 1). The proportion of patients seen in neurology and primary care clinics was similar regardless of ATTR-CM status. Patients with ATTR-CM were also more likely to be seen in other clinics than HF patients without ATTR-CM. Among all visits in the ‘other’ category, the most common type of clinic visits for ATTR-CM patients in the 6 months prior to HF hospitalization were nurse practitioner visits (22.5%), physician assistant visits (7.8%) and nephrology visits (7.2%). The most common types of visits for HF patients without ATTR-CM were nurse practitioner visits (21.8%), physician assistant visits (10.2%), and podiatry visits (6.7%). In the 6 months after HF hospitalization, the most common types of other visits for patients with ATTR-CM were nurse practitioner visits (27.7%), nephrology visits (9.2%), and physician assistant visits (7.7%). Corresponding visits for patients without ATTR-CM were nurse practitioner (28.7%), physician assistant visits (10.7%), and nephrology visits (7.2%). Among older US adults hospitalized for HF, regardless of ATTR-CM status, patients were seen 5–7 times in an outpatient clinic during the 6 months before hospitalization, and a comparable number of times in the 6 months after hospitalization. Compared with HF without ATTR-CM, those with ATTR-CM tended to have more frequent visits, driven by higher rates of cardiology and other subspecialty visits. In aggregate, these data suggest ample outpatient opportunities for optimizing disease-modifying therapies before and after HF hospitalization, for both patients with and without ATTR-CM. While underuse and underdosing of guideline-directed medical therapy for HF have been repeatedly seen, the explanation for these gaps remains debated.4–6 Some have suggested that insufficient outpatient follow-up and/or limited clinic schedule availability and workflows are significant barriers to initiation and titration of disease-modifying therapy. The current data from older patients with HF in US clinical practice do not support a lack of clinic visits as a widespread major problem. Rather, we observed several in-person clinic visits in the months before and after HF hospitalization, and most patients were seen in the clinic by a cardiologist. These data are concordant with prior studies suggesting that clinical inertia and underappreciation of clinical risk, rather than a lack of clinic visit opportunities, are the primary reasons clinicians do not initiate and titrate GDMT for HF.7,8 Specifically for patients with ATTR-CM, the current study highlights these patients as particularly likely to have a substantial number of clinic visit opportunities to initiate disease-modifying therapy. Such visits may not be as relevant to the prescription of non-amyloid specific GDMT for HF, since data for use of these therapies in patients with established ATTR-CM are limited.9,10 Yet, for patients with ATTR-CM, frequent outpatient visits, including among cardiology and neurology specialists, may represent opportunities to prescribe therapies such as TTR stabilizers and silencers. Limitations of this study should be noted. First, data regarding outpatient prescription drug use (e.g. Medicare Part D) were not available. Thus, associations between frequency of outpatient visits and actual medication utilization could not be explored. Nonetheless, prior studies have established significant gaps in outpatient use of disease-modifying therapy for HF. Likewise, rates of GDMT prescription at discharge among patients without ATTR-CM in the current study were low, consistent with likely low rates of upstream pre-hospitalization use. In the current analysis, it was possible to scan outpatient claims (Medicare Part B) for use of TTR silencers. Only