Highlights
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A web-based questionnaire survey revealed that only 15% of Japanese cardiologists were satisfied with their daily clinical practice for patients with ischemia with nonobstructive coronary artery disease (INOCA), and approximately 54% reported clinical experience with fewer than 10 INOCA patients, similar to the findings from a previous survey conducted in the United States.
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Beta-blockers, regarded as the first-line medical therapy for coronary microvascular dysfunction (CMD), were used always or often by only 36% cardiologists, in contrast to calcium channel blockers, which were chosen for vasospastic angina in more than 90% of cases.
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The prescription of beta-blockers for the CMD endotype and specialization in interventional cardiology were associated with an increased odds ratio for being satisfied with INOCA management.
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Cardiologists who were satisfied were more likely to pay attention to the presence of CMD and order physiological assessments using a pressure wire.
The appropriate management of ischemia with nonobstructive coronary artery disease (INOCA) has now become a globally recognized issue. However, there is a lack of studies examining how cardiologists manage INOCA by differentiating between vasospastic angina and coronary microvascular dysfunction (CMD) endotypes in real clinical practice, as well as the extent to which they are satisfied with their current diagnostic and management approaches. This survey collected data through a web-based questionnaire conducted between October 15, 2024, and November 15, 2024, targeting Japanese cardiologists who were members of a cardiology-specific website. In total, 158 cardiologists responded to the survey. Approximately 54% of the cardiologists reported having clinical experience with <10 INOCA patients. Only 15% reported being very satisfied or satisfied with the management of INOCA. Cardiologists prescribing or recommending beta-blockers for CMD endotype patients exhibited significantly higher odds of INOCA management satisfaction (OR, 3.80; 95% CI 1.38 to 11.2; p = 0.0047). Furthermore, specialization in interventional cardiology was associated with increased odds (OR, 5.97; 95% CI 1.67 to 32.7; p = 0.0016), and satisfied cardiologists were significantly more likely to pay more attention to the presence of CMD (p = 0.017) and order physiological assessments (p = 0.026). Although awareness of INOCA is growing, overall satisfaction with its clinical management remains low among cardiologists. Those who are more attentive to CMD and differentiate among INOCA endotypes tend to report higher satisfaction. In conclusion, these findings highlight the need for additional research and better dissemination of diagnostic and treatment strategies to improve quality of care.
Ischemia with nonobstructive coronary artery disease (INOCA) represents a significant clinical challenge in contemporary cardiology, and this is a condition that cardiologists frequently encounter in daily clinical practice. According to a report from the United States National Cardiovascular Data Registry, approximately 63% of patients presenting with angina symptoms do not have obstructive lesions and are classified as having INOCA. Despite the large number of cases, a survey of 172 respondents conducted through the American College of Cardiology CardioSurve Panel revealed marked heterogeneity in the clinical approaches to INOCA among United States cardiologists.
INOCA encompasses 2 major endotypes: vasospastic angina (VSA) and coronary microvascular dysfunction (CMD). VSA is primarily diagnosed through spasm provocation testing, and CMD through physiological assessments, both of which require coronary catheterization. CMD is assessed in the Japanese guideline using fractional flow reserve (FFR), coronary flow reserve (CFR), and index of microcirculatory resistance (IMR), with cutoff values of >0.80, <2.0, and ≥25, respectively. In particularly, a meta-analysis showed that CMD is associated with an approximately 4-fold increase in the odds risk of mortality. Therefore, identifying the presence or absence of CMD represents a key component in the INOCA management from the perspective of tailored treatment strategies. According to the principal recommendations, calcium channel blockers (CCBs) are considered the first-line agents for VSA, whereas beta-blockers are regarded as the first-line medical therapy for CMD. , Several clinical studies have highlighted the benefits of distinguishing between the 2 endotypes to facilitate more effective treatment strategies. The CorMicA trial, the first randomized controlled trial to assess the clinical use of stratified management based on comprehensive invasive coronary functional testing, demonstrated the benefits of a precision medicine approach in INOCA management. Further evidence suggests that such diagnostic testing often leads to changes in clinical management and substantially reduces the misdiagnosis of VSA or CMD. Such evidence has increasingly emerged, and guidelines from around the world—including Japan— recommend identifying and treating VSA and CMD separately. However, to date, few studies have investigated current clinical practice differentiating between the 2 endotypes of INOCA or examined practice variations among cardiologists. This survey aimed to investigate whether, in the management of INOCA in real clinical practice, therapeutic approaches guided by diagnostic options for differentiating between VSA and CMD vary with the level of management satisfaction.
Methods
Study population
The INOCA Management and Awareness Insights—Questions and Answers Survey (INOMAI-QA Survey) investigated the association between daily clinical practice and physician satisfaction among Japanese cardiologists using a web-based questionnaire conducted using TCROSS NEWS, which is a medical website dedicated to cardiovascular medicine. Details regarding TCROSS NEWS have been described in previous studies. , This platform specializes in cardiovascular medicine with approximately 90% of its medical doctor members being cardiologists. This study included medical professional members who had consented to receive the e-newsletter or directly visit the website between October 15, 2024, and November 15, 2024.
Survey details
This focused survey was developed by researchers with experience and expertise in the cardiovascular field and survey design, and was independently reviewed by an expert clinician specializing in cardiology at TCROSS Co., Ltd. Google Forms was used to conduct the online survey. Supplementary Table 1 presents the questionnaires. The web-based questionnaire included 39 items, such as participants’ demographics, institutional affiliation, practice status of INOCA, level of satisfaction with current management and diagnosis options, approach to daily clinical practice, and other factors that might influence their practice.
Participant demographics included institution type, sex, time in practice distribution, professional specialty, number of percutaneous coronary interventions personally performed in the past year, and cumulative number of patients with INOCA managed throughout their practice. The institutional status was examined based on the number of coronary angiography (CAG) performed annually at the institution, the number of cardiologists, and the accessibility of CMD testing. Although CMD testing using pressure guidewire is available at 267 certified institutions in Japan, its adoption remains inconsistent and limited in certain regions. The current status of satisfaction with INOCA management includes the frequency of awareness regarding the presence or absence of CMD and satisfaction with the current methods of diagnosing and managing INOCA. The opinions regarding the current INOCA practice include the frequency of various diagnostic tests and the status of prescription practices and recommendation levels for both patients with VSA and CMD. As a management strategy for patients with INOCA, the recommendations include the degree of combination medications, the follow-up interval from the initial assessment or diagnosis, and the indicators used in determining the management plan.
All questions were asked in a multiple-choice form. Ordinal categorical variables were evaluated using a 5-point Likert-type scale. Only responses from participants verified as physicians through cross-checking with TCROSS NEWS membership information were included in the final analysis.
Statistical analysis
Baseline characteristics were summarized using descriptive statistics. Respondents were divided into the “satisfied” (very satisfied/satisfied) and “nonsatisfied” (neutral/dissatisfied/very dissatisfied) groups, based on their self-reported satisfaction with INOCA management. Likert scale items were treated as ordinal variables for group comparisons. Frequencies and percentages were calculated, and Fisher’s exact test was used to compare the distribution, with a significance level set at p <0.05. When analyzing a 2 × 2 table, the 2-sided Fisher’s exact test and the usual exact confidence interval (CI) for the odds ratio (OR) were presented. Polychoric correlations were calculated assuming that the 5-point Likert-type scale approximates an interval scale. Correlation coefficients were estimated using the polychoric() function from the R psych package, with an absolute threshold of 0.4. , Bootstrap percentile-based 95% CIs were computed using 2,000 replications. , All statistical analyses were performed using R (version 4.5.0).
Results
Scope of practice
In total, 162 respondents participated in the survey, of whom 158 were confirmed to be cardiologists and provided valid responses. Among these, 46% (73/158) reported having previously managed ≥10 patients with INOCA. Time in practice, which refers to physician’s career, was categorized as follows: Early Career (1 to 5 years), Mid-Early Career (6 to 10 years), Mid-Late Career (11 to 15 years), and Late Career (≥16 years). More than half of the respondents (54%, 85/158) had over 16 years of clinical experience, and 59% (93/158) reported interventional cardiology as their specialty, primarily involving the treatment of cardiovascular diseases. Regarding the annual number of CAG procedures at their affiliated institution—used here as an indicator of the potential to identify INOCA patients—8.9% (14/158) reported that no such procedures were performed. With respect to the availability of CMD testing, 66% (103/157) indicated that such testing was accessible at their institutions ( Table 1 ).
Table 1
Baseline characteristics
| Characteristic | Overall ( N = 158) |
|---|---|
| Hospital types | |
| University hospital | 33 (21%) |
| General hospital | 102 (65%) |
| Cardiovascular hospital | 15 (9.5%) |
| Clinic without Bed | 8 (5.1%) |
| Sex | |
| Male | 147 (93%) |
| Female | 11 (7.0%) |
| Time in practice, y | |
| Early Career (1 to 5 y) | 11 (7.0%) |
| Mid-Early Career (6 to 10 y) | 20 (13%) |
| Mid-Late Career (11 to 15 y) | 42 (27%) |
| Late Career (≥16 y) | 85 (54%) |
| Field of expertise | |
| Interventional cardiology | 93 (59%) |
| General cardiology | 41 (26%) |
| Heart failure | 9 (5.7%) |
| Structural heart disease | 7 (4.4%) |
| Other 1) | 8 (5.1%) |
| Annual CAG count per site | |
| ≥2501 | 3 (1.9%) |
| 1201 to 2500 | 7 (4.4%) |
| 601 to 1200 | 40 (25%) |
| 301 to 600 | 55 (35%) |
| 1 to 300 | 39 (25%) |
| None performed | 14 (8.9%) |
| Annual PCI case volume per individual | |
| ≥151 | 10 (6.3%) |
| 101 to 150 | 12 (7.6%) |
| 51 to 100 | 50 (32%) |
| 1 to 50 | 68 (43%) |
| None performed | 18 (11%) |
| No. of cardiologists | |
| Large (≥26) | 16 (10%) |
| Medium (11 to 25) | 45 (28%) |
| Medium small (5 to 10) | 55 (35%) |
| Small (1 to 4) | 42 (27%) |
| No. of INOCA practices | |
| ≥100 | 3 (1.9%) |
| 10 to 99 | 70 (44%) |
| <10 | 73 (46%) |
| Never | 12 (7.6%) |
| Access to CMD testing | |
| Yes | 103 (66%) |
| No | 54 (34%) |
| Not sure | 1 |
1) Other includes Echocardiography ( n = 3), Arrhythmia ( n = 2), Emergency medicine ( n = 1), Psychiatry ( n = 1), and Internal medicine ( n = 1).
CAG = coronary angiography; CMD = coronary microvascular dysfunction; INOCA = ischemia with nonobstructive coronary artery disease; PCI = percutaneous coronary intervention.
Overview of INOCA diagnosis options
When managing patients with suspected INOCA, most cardiologists (89%; 141/158) always/often ordered transthoracic echocardiogram. In contrast, only 18% (29/158) always/often ordered stress single-photon emission computed tomography. Regarding invasive catheter-based diagnostic testing, approximately 61% (96/158) always/often ordered CAG, approximately half (47%; 75/158) ordered invasive coronary function testing as a physiological assessment, and 49% (77/158) ordered spasm provocation testing ( Supplementary Figure 1 ).
Medical management overview of VSA and CMD
For VSA, nearly all cardiologists (93%; 147/158) reported always/often prescribing or recommending CCBs, followed by nitrates (63%; 100/158), nicorandil (50%; 79/158), and statins (54%; 85/158). In contrast, beta-blockers were rarely prescribed or recommended (7%; 11/158), and angiotensin-converting enzyme inhibitors/angiotensin receptor blocker (ACEi/ARB) (9%; 14/158) and antiplatelet agents (14%; 22/158) were prescribed or recommended much less frequently. Among cardiologists managing VSA, approximately 3 of 5 reported always/often prescribing or recommending nitrates, approximately half did so for nicorandil, and nearly all used CCBs. In contrast, <10% reported routinely prescribing or recommending beta-blockers or ACEi/ARB ( Figure 1 ).
Prescribing practices or recommendations for the management of vasospastic angina, as reported by surveyed cardiologists. The Top2 box represents the combined proportion of respondents selecting the top 2 categories on a Likert scale. Each proportion was rounded to 1 decimal place, and the Top2 box value was calculated by summing these 1-decimal-place values and then rounding the total to the nearest whole number. ACEi = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; CCBs = calcium channel blockers.
For CMD, 65% (103/158) of the cardiologists always/often prescribed or recommended CCBs, whereas approximately 36% (57/158) always/often prescribed or recommended beta-blockers. Similar to VSA, approximately half of the cardiologists prescribed or recommended nicorandil (51%; 80/158) and statins (53%; 83/158); however, ACEi/ARB (17%; 27/158) and antiplatelet agents (16%; 26/158) were rarely administered ( Figure 2 ).
Prescribing practices or recommendations for the management of coronary microvascular dysfunction, as reported by surveyed cardiologists. The definition and calculation of the Top2 box, as well as all abbreviations, are provided in Figure 1 .
INOCA management satisfaction and related factors
Overall, approximately 15% (24/158) reported being very satisfied/satisfied with INOCA management ( Supplementary Figure 2 ). For VSA, the use of INOCA-related medications did not differ between satisfied and nonsatisfied groups. In contrast, cardiologists using or recommending beta-blockers for CMD endotype patients exhibited significantly higher odds of INOCA management satisfaction (OR, 3.80; 95% CI 1.38 to 11.2; p = 0.0047) ( Table 2 ). Additionally, beta-blockers were always/often used or recommended by satisfied cardiologists for CMD (p = 0.033), and the odds ratio of being satisfied increased with increasing the frequency ( Figure 3 ).
Table 2
Association between frequent medication use (Always/Often) and higher satisfaction with INOCA management (Very satisfied/Satisfied): 2 × 2 table and odds ratios
| Odds ratio (95%CI) | p-value | |
|---|---|---|
| VSA | ||
| Nitrates | 0.52 (0.20 to 1.39) | 0.17 |
| Beta-blockers | 0.54 (0.012 to 4.11) | 1.0 |
| CCBs | 1.85 (0.24 to 83.9) | 1.0 |
| ACEi/ARB | 1.74 (0.29 to 7.48) | 0.42 |
| Nicorandil | 1.0 (0.38 to 2.63) | 1.0 |
| Statin | 1.85 (0.69 to 5.35) | 0.27 |
| Antiplatelets | 1.26 (0.28 to 4.42) | 0.75 |
| CMD | ||
| Nitrates | 0.42 (0.12 to 1.28) | 0.11 |
| Beta-blockers | 3.80 (1.38 to 11.2) | 0.0047 |
| CCBs | 0.68 (0.26 to 1.86) | 0.48 |
| ACEi/ARB | 2.37 (0.73 to 7.10) | 0.13 |
| Nicorandil | 0.42 (0.14 to 1.12) | 0.075 |
| Statin | 1.52 (0.57 to 4.23) | 0.38 |
| Antiplatelets | 1.44 (0.38 to 4.64) | 0.55 |
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