Pericardiotomy as a novel treatment for heart failure with preserved ejection fraction.

The pericardium plays an important role in modulating cardiac performance and hemodynamics in patients with heart failure with preserved ejection fraction (HFpEF). Pericardial constraint increases filling pressures in patients with HFpEF, particularly those with the obesity phenotype, atrial myopathy, right ventricular dysfunction, and tricuspid regurgitation. Preclinical and early stage clinical studies indicate that pericardiotomy may become a novel treatment for HFpEF. This review summarizes and discusses the pathophysiology of pericardial restraint and the possibility of pericardiotomy in HFpEF.

Impact of perioperative change in physical function on midterm outcomes after transcatheter aortic valve implantation.

Preoperative frailty diminishes the potential for functional recovery after transcatheter aortic valve implantation (TAVI). However, perioperative changes in physical status and their impact on prognosis after TAVI have not previously been reported. Therefore, this study aimed to investigate whether perioperative changes in physical function affect prognosis in patients undergoing TAVI. We retrospectively reviewed 257 patients who underwent TAVI. The Short Physical Performance Battery (SPPB), an objective physical status assessment tool, was evaluated pre- and post-TAVI. Patients were divided into two groups: (i) patients whose SPPB score declined in the perioperative period (the decline group) and (ii) patients whose SPPB score did not decline in the perioperative period (the non-decline group). The primary endpoint was unplanned hospitalization owing to heart failure or cardiovascular death following TAVI. The mean follow-up period was 385 ± 151 days, mean age was 83.2 ± 5.8 years, and 67% of the patients were women. Sixteen patients required readmission owing to heart failure, and seven experienced cardiovascular-related death. Kaplan-Meier analysis revealed that the event-free rate was significantly lower in the decline group (log-rank, p = 0.006). A stepwise multivariate logistic regression analysis showed that a perioperative change in SPPB was significantly associated with primary endpoints (odds ratio, 1.51; 95% confidence interval, 1.12-2.04). Perioperative change in physical function was an independent risk factor for heart failure, hospitalization, or cardiovascular death following TAVI.

Per-Vessel Level Analysis of Fractional Flow Reserve and Instantaneous Wave-Free Ratio Discordance　- Insights From the AJIP Registry.

BACKGROUND: The per-vessel level impact of physiological pattern of disease on the discordance between fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) has not been clarified.Methods and Results:Using the AJIP registry, vessels with FFR/iFR discordance (133/671 [19.8%]) were analyzed. In the left anterior descending artery (LAD), physiologically diffuse disease, as assessed by pressure-wire pullback, was associated with FFR-/iFR+ (83.3% [40/48]), while physiologically focal disease was associated with FFR+/iFR- (57.4% [31/54]), significantly (P<0.0001). These differences were not significant in non-LAD (P=0.17). CONCLUSIONS: The impact of physiological pattern of disease on FFR/iFR discordance is more pronounced in the LAD.

Palliative Care in Patients with Advanced Heart Failure.

The heart failure (HF) guidelines recommend palliative care; however, it can often be difficult to determine the timing of palliative care referral. Because HF with fluid retention and low-cardiac output may trigger several unpleasant symptoms, continuous HF treatment is required to alleviate these symptoms in advanced HF. The patients with HF often suffer from total pain; therefore, the support from a multidisciplinary team plays a crucial role to improve quality of life of the patients and their families not only in the terminal phase but also from the early stage.

Novel Use of GuideLiner with a Low-Profile Balloon for the Retrieval of Disrupted Balloon Catheter.

We report a case of successful percutaneous retrieval of an unexpectedly disrupted balloon catheter using GuideLiner and a low-profile balloon. The procedure and the mechanism of this novel technique were described in detail with ex-vivo testing. This case demonstrated the utility of the combination of GuideLiner and low-profile balloon as a bail-out for intravascular foreign body.

Autoimmune Disorders in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Inflammation plays a fundamental role in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). In most patients, inflammation develops secondary to cardiometabolic comorbidities, but in some, HFpEF develops in the setting of an underlying systemic inflammatory disease such as rheumatoid arthritis or systemic lupus erythematosus. OBJECTIVES: This study aimed to investigate the prevalence, pathophysiology, and outcome of patients with HFpEF and autoimmune or primary inflammatory disorders. METHODS: Of 982 consecutively evaluated patients with HFpEF diagnosed, 79 (8.0%) had autoimmune disorders. HFpEF was defined by invasive cardiopulmonary hemodynamic exercise testing. RESULTS: Female sex, higher heart rate, lower hemoglobin, absence of atrial fibrillation, and absence of coronary artery disease were independently associated with autoimmune disorders. Hemodynamics at rest and exercise did not differ between the groups, but peripheral oxygen extraction was lower in those with autoimmune disorders, reflected by lower arterial-venous oxygen content difference at rest (4.2 ± 0.7 mL/dL vs 4.6 ± 1.0 mL/dL; P < 0.001) and during exercise (9.3 ± 2.2 mL/dL vs 10.4 ± 2.2 mL/dL; P < 0.001), suggesting a greater peripheral deficit, and ventilatory efficiency (VE/VCo2 slope, regression slope relating minute ventilation to carbon dioxide output) was also more impaired (38.0 ± 7.9 vs 36.2 ± 7.3; P = 0.043). Patients with autoimmune disorders had a higher risk of death or heart failure (HF) hospitalization compared with those without in adjusted analyses (HR: 1.95 [95% CI: 1.17-3.27]; P = 0.011) over a median follow-up of 3.0 years, which was primarily attributable to higher risk of HF hospitalization (HR: 2.87 [95% CI: 1.09-7.57]; P = 0.033). CONCLUSIONS: Patients with HFpEF and autoimmune disorders have similar hemodynamic derangements but greater peripheral deficits in oxygen transport and higher risk for adverse outcome compared with those without.

Prevalence, Incidence, and Outcomes of Diastolic Dysfunction in Isolated Tricuspid Regurgitation: Perhaps Not Really "Isolated"?

BACKGROUND: In the absence of left-sided cardiac/pulmonary disease, functional tricuspid regurgitation (FTR) is referred to as isolated or idiopathic. Relationships between left ventricular diastolic dysfunction (DD) and FTR remain unknown. OBJECTIVES: The purpose of this study was to investigate the prevalence, incidence, and outcome of DD in patients with idiopathic FTR. METHODS: Adults without structural heart disease were identified. Severe DD was defined by ≥3 of 4 abnormal DD parameters (medial e', medial E/e', TR velocity, left atrial volume index) and ≥ moderate DD by ≥2. Propensity-score matching was performed (3:1) between each less-than-severe TR group and severe TR based on age, sex, body mass index, and comorbidities. RESULTS: Among 30,428 patients, FTR was absent in 73%, mild in 22%, moderate in 4%, and severe in 0.4%. In the propensity-matched sample, severe DD was present in 2%, 6%, 9%, and 13% patients, and ≥ moderate DD in 11%, 18%, 28%, and 48%, respectively (P < 0.001). The probability of heart failure with preserved ejection fraction using the H2FPEF score increased with increasing FTR (median 29.7%, 45.5%, 61.4%, and 88.7%, respectively), as did the prevalence of impaired left atrial strain <24% (35%, 48%, and 69% in mild, moderate, and severe TR). Incident severe and ≥ moderate DD developed more frequently with increasing FTR (HR: 8.45 [95% CI: 2.60-27.50] and HR: 2.82 [95% CI: 1.40-5.69], respectively for ≥ moderate vs no FTR) over a median of 3.0 years. Findings were confirmed in patients without lung disease or right ventricular enlargement. Over a median of 5.0 years, patients with ≥ moderate FTR and DD had the greatest risk of worse outcomes (multivariable P < 0.001). The association between TR and adverse outcomes was significantly diminished in the absence of DD. CONCLUSIONS: Diastolic dysfunction, increased heart failure with preserved ejection fraction probability, and impaired left atrial strain are commonly present in patients with idiopathic FTR, suggesting that the latter may not be truly isolated. Patients with FTR without DD or heart failure are at increased risk of incident DD. Patients with FTR and DD display worse outcomes.

Clinical phenogroup diversity and multiplicity: Impact on mechanisms of exercise intolerance in heart failure with preserved ejection fraction.

AIMS: We aimed to clarify the extent to which cardiac and peripheral impairments to oxygen delivery and utilization contribute to exercise intolerance and risk for adverse events, and how this relates to diversity and multiplicity in pathophysiologic traits. METHODS AND RESULTS: Individuals with heart failure with preserved ejection fraction (HFpEF) and non-cardiac dyspnoea (controls) underwent invasive cardiopulmonary exercise testing and clinical follow-up. Haemodynamics and oxygen transport responses were compared. HFpEF patients were then categorized a priori into previously-proposed, non-exclusive descriptive clinical trait phenogroups, including cardiometabolic, pulmonary vascular disease, left atrial myopathy, and vascular stiffening phenogroups based on clinical and haemodynamic profiles to contrast pathophysiology and clinical risk. Overall, patients with HFpEF (n = 643) had impaired cardiac output reserve with exercise (2.3 vs. 2.8 L/min, p = 0.025) and greater reliance on peripheral oxygen extraction augmentation (4.5 vs. 3.8 ml/dl, p < 0.001) compared to dyspnoeic controls (n = 219). Most (94%) patients with HFpEF met criteria for at least one clinical phenogroup, and 67% fulfilled criteria for multiple overlapping phenogroups. There was greater impairment in peripheral limitations in the cardiometabolic group and greater cardiac output limitations and higher pulmonary vascular resistance during exertion in the other phenogroups. Increasing trait multiplicity within a given patient was associated with worse exercise haemodynamics, poorer exercise capacity, lower cardiac output reserve, and greater risk for heart failure hospitalization or death (hazard ratio 1.74, 95% confidence interval 1.08-2.79 for 0-1 vs. ≥2 phenogroup traits present). CONCLUSIONS: Though cardiac output response to exercise is limited in patients with HFpEF compared to those with non-cardiac dyspnoea, the relative contributions of cardiac and peripheral limitations vary with differing numbers and types of clinical phenotypic traits present. Patients fulfilling criteria for greater multiplicity and diversity of HFpEF phenogroup traits have poorer exercise capacity, worsening haemodynamic perturbations, and greater risk for adverse outcome.

Cardiac function, haemodynamics, and valve competence with exercise in patients with heart failure with preserved ejection fraction and mild to moderate secondary mitral regurgitation.

AIMS: This study aimed to evaluate the clinical significance of secondary mitral regurgitation (MR) in patients with heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: We conducted a prospective study enrolling consecutively evaluated patients with HFpEF undergoing invasive haemodynamic exercise testing with simultaneous echocardiography. Compared to HFpEF without MR (n = 145, 79.7%), those with mild or moderate MR (n = 37, 20.3%) were older, more likely to be women, had more left ventricular (LV) systolic dysfunction, and more likely to have left atrial (LA) myopathy reflected by greater burden of atrial fibrillation, more LA dilatation, and poorer LA function. Pulmonary artery (PA) wedge pressure was higher at rest in HFpEF with MR (17 ± 5 mmHg vs. 20 ± 5 mmHg, p = 0.005), but there was no difference with exercise. At rest, only 2 (1.1%) patients had moderate MR, and none developed severe MR. Pulmonary vascular resistance was higher, and right ventricular (RV)-PA coupling was more impaired in patients with HFpEF and MR at rest and exercise. LV and LA myocardial dysfunction remained more severe in patients with MR during stress compared to those without MR, characterized by greater LA dilatation during all stages of exertion, lower LA emptying fraction and compliance, steeper and rightward-shifted LA pressure-volume relationships, and reduced LV longitudinal contractile function. CONCLUSIONS: Patients with HFpEF and mild or moderate MR have more severe LV systolic dysfunction, LA myopathy, RV-PA uncoupling, and more severe pulmonary vascular disease. Mitral valve incompetence in this setting is a phenotypic marker of more advanced disease but is not a causal factor in development of HFpEF.

CORRIGENDUM: Preprocedural Controlling Nutritional Status Score as a Predictor of Mortality in Patients Undergoing Transcatheter Mitral Valve Repair　- A Single Center Experience in Japan.

[This corrects the article DOI: 10.1253/circrep.CR-23-0055.].

Physiological Assessment with iFR prior to FFR Measurement in Left Main Disease.

Despite guideline-based recommendation of the interchangeable use of instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) to guide revascularization decision-making, iFR/FFR could demonstrate different physiological or clinical outcomes in some specific patient or lesion subsets. Therefore, we sought to investigate the impact of difference between iFR and FFR-guided revascularization decision-making on clinical outcomes in patients with left main disease (LMD). In this international multicenter registry of LMD with physiological interrogation, we identified 275 patients in whom physiological assessment was performed with both iFR/FFR. Major adverse cardiovascular event (MACE) was defined as a composite of death, non-fatal myocardial infarction, and ischemia-driven target lesion revascularization. The receiver-operating characteristic analysis was performed for both iFR/FFR to predict MACE in respective patients in whom revascularization was deferred and performed. In 153 patients of revascularization deferral, MACE occurred in 17.0% patients. The optimal cut-off values of iFR and FFR to predict MACE were 0.88 (specificity:0.74; sensitivity:0.65) and 0.76 (specificity:0.81; sensitivity:0.46), respectively. The area under the curve (AUC) was significantly higher for iFR than FFR (0.74; 95%CI 0.62-0.85 vs. 0.62; 95%CI 0.48-0.75; p = 0.012). In 122 patients of coronary revascularization, MACE occurred in 13.1% patients. The optimal cut-off values of iFR and FFR were 0.92 (specificity:0.93; sensitivity:0.25) and 0.81 (specificity:0.047; sensitivity:1.00), respectively. The AUCs were not significantly different between iFR and FFR (0.57; 95%CI 0.40-0.73 vs. 0.46; 95%CI 0.31-0.61; p = 0.43). While neither baseline iFR nor FFR was predictive of MACE in patients in whom revascularization was performed, iFR-guided deferral seemed to be safer than FFR-guided deferral.

Speech-induced Atrial Tachycardia with Presyncope.

Speech-induced atrial tachycardia (AT) with presyncope is extremely rare. A 52-year-old woman employed at a supermarket reported recurrent presyncope while speaking out loud at her job. Holter electrocardiography revealed AT while swallowing without presyncope. The patient's blood pressure decreased during AT, and she experienced presyncope while saying "IRASSHAIMASE" loudly during a tilt table test. Accordingly, bisoprolol 1.25 mg was prescribed, and the patient did not experience episodes of presyncope with recurrence of AT for 2 years. This case suggests that provocation of arrhythmia in the tilting position may be useful for demonstrating a relationship between arrhythmia and presyncope and/or syncope.

Swallowing-induced Atrial Tachycardia with a Thymic Cyst.

We herein report a 34-year-old man who presented with recurrent palpitations that occurred while swallowing solid food. Holter monitoring revealed atrial tachycardia (AT) while eating. In addition, chest computed tomography (CT) showed a small nodule in the front of the ascending aorta. Thoracoscopic surgery was performed to remove the nodule; a pathological examination revealed that the nodule was a thymic cyst. The AT disappeared postoperatively. This case demonstrates that a mediastinal nodule can cause swallowing-induced AT.

Noteworthy sequelae after COVID-19 pneumonia in a patient with heart failure due to cardiomyopathy.

Coronavirus disease 2019 (COVID-19) is endemic worldwide. Cardiovascular disease, particularly myocarditis, is one of the most common comorbidities in patients with COVID-19. However, heart failure due to COVID-19-triggered cardiomyopathy is not well understood. Additionally, "pseudo" heart failure symptoms have been reported in patients with a compensated condition, in which the heart works well enough that symptoms are unnoticeable or very easy to manage. Here, we report a case of heart failure due to cardiomyopathy in a patient with COVID-19 and postural orthostatic tachycardia syndrome after heart failure treatment. Learning objective: Postural orthostatic tachycardia syndrome (POTS) symptoms after coronavirus disease 2019 may be mistaken for heart failure symptoms; thus, it is essential to suspect POTS when symptoms such as shortness of breath and palpitations are noted upon standing, along with the relevant physical findings.

Effects of temperature and humidity on cerebrovascular disease hospitalization in a super-aging society.

Weather conditions influence the incidence of cardiovascular disease. However, few studies have investigated the association between weather temperature and humidity and cerebrovascular disease hospitalizations in a super-aging society. We included 606,807 consecutive patients with cerebrovascular disease admitted to Japanese acute-care hospitals between 2015 and 2019. The primary outcome was the number of cerebrovascular disease hospitalizations per day. Multilevel mixed-effects linear regression models were used to estimate the association of mean temperature and humidity, 1 day before hospital admission, with cerebrovascular disease hospitalizations, after adjusting for air pollution, hospital, and patient demographics. Lower mean temperatures and humidity < 70% or humidity ≧ 70% are associated with an increased incidence of cerebrovascular disease hospitalization (coefficient, - 1.442 [- 1.473 to - 1.411] per °C, p < 0.001, coefficient, - 0.084 [- 0.112 to - 0.056] per%, p < 0.001, and coefficient, 0.136 [0.103 to 0.168] per %, p < 0.001, respectively). Lower mean temperatures and extremely lower or higher humidity are associated with an increased incidence of cerebrovascular disease hospitalization in a super-aging society.

Efficacy and Safety of Home-Based Cardiac Telemonitoring Rehabilitation in Patients After Transcatheter Aortic Valve Implantation: Single-Center Usability and Feasibility Study.

BACKGROUND: No consensus exists on the efficacy of home-based cardiac rehabilitation (CR) in patients who have undergone transcatheter aortic valve implantation (TAVI). Additionally, there are no reports on home-based cardiac telemonitoring rehabilitation (HBTR) in patients after TAVI. OBJECTIVE: We aimed to investigate the efficacy of HBTR in patients who have undergone TAVI. METHODS: This single-center preliminary study introduced HBTR to patients after TAVI, and the efficacy outcomes of the rehabilitation method were compared to that of a historical control cohort. The historical control cohort (control group) consisted of 6 consecutive patients who underwent ordinary outpatient CR after TAVI from February 2016 to March 2020. Patients who participated in the HBTR program were only recruited after the TAVI procedure and before discharge between April 2021 and May 2022. In the first 2 weeks after TAVI, patients underwent outpatient CR and were trained using telemonitoring rehabilitation systems. Thereafter, patients underwent HBTR twice a week for 12 weeks. The control group performed standard outpatient CR at least once a week for 12 to 16 weeks. Efficacy was assessed using peak oxygen uptake (VO2) prior to and after CR. RESULTS: Eleven patients were included in the HBTR group. All patients underwent 24 HBTR sessions during the 12-week training period, and no adverse events were observed. The control group participants performed 19 (SD 7) sessions during the training period, and no adverse events were observed. Participants in the HBTR and control groups had a mean age of 80.4 (SD 6.0) years and 79.0 (SD 3.9) years, respectively. In the HBTR group, preintervention and postintervention peak VO2 values were 12.0 (SD 1.7) mL/min/kg and 14.3 (SD 2.7) mL/min/kg (P=.03), respectively. The peak VO2 changes in the HBTR and control groups were 2.4 (SD 1.4) mL/min/kg and 1.3 (SD 5.0) mL/min/kg (P=.64), respectively. CONCLUSIONS: Home-based CR using a telemonitoring system is a safe outpatient rehabilitation method. Its efficacy is not inferior to that of standard CR in patients who have undergone TAVI. TRIAL REGISTRATION: Japan Registry of Clinical Trials jRCTs032200122; https://jrct.niph.go.jp/latest-detail/jRCTs032200122.

Preprocedural Controlling Nutritional Status Score as a Predictor of Mortality in Patients Undergoing Transcatheter Mitral Valve Repair　- A Single Center Experience in Japan.

Background: A high score for controlling nutritional status (CONUT) due to poor nutritional status has been associated with adverse outcomes in patients with chronic heart failure. However, because little is known about the effect of CONUT score on mortality rates after transcatheter mitral valve repair, we evaluated nutrition screening tools for prognosis prediction in patients undergoing transcatheter mitral valve repair using the MitraClipTM system. Methods and Results: We retrospectively analyzed 148 patients with severe mitral regurgitation (MR) who underwent MitraClipTM implantation between April 2018 and April 2021. The preprocedural CONUT scores were assessed at the time of hospitalization, the primary outcome was all-cause death, and the analysis was of the mortality and incidence rates of cardiac events 1 year post-operation. Functional MR was of ischemic origin in the majority of patients (69.6%), with a mean left ventricular ejection fraction of 48.9±15.8%. Kaplan-Meier curves indicated that all-cause death was significantly worse in the high-CONUT score group than in the low-CONUT score group. Cox hazard analysis showed a significant association between all-cause death and CONUT score, as well as MitraScore. Conclusions: Preprocedural CONUT score, as well as MitraScore, in patients undergoing transcatheter edge-to-edge mitral valve repair may predict an increased risk of all-cause death. This knowledge should allow the heart team to accurately assess the clinical implications and prognostic benefits of the procedure in individual patients.

Physiology-guided PCI versus CABG for left main coronary artery disease: insights from the DEFINE-LM registry.

There have been no studies comparing clinical outcomes of physiology-guided revascularization in patients with unprotected left main coronary disease (ULMD) between percutaneous coronary intervention (PCI) vs. coronary artery bypass grafting (CABG). The aim of this study was to assess the long-term clinical outcomes between PCI and CABG of patients with physiologically significant ULMD. From an international multicenter registry of ULMD patients interrogated with instantaneous wave-free ratio (iFR), we analyzed data from 151 patients (85 PCI vs. 66 CABG) who underwent revascularization according to the cutoff value of iFR ≤ 0.89. Propensity score matching was employed to adjust for baseline clinical characteristics. The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, and ischemia-driven target lesion revascularization. The secondary endpoints were the individual components of the primary endpoint. Mean age was 66.6 (± 9.2) years, 79.2% male. Mean SYNTAX score was 22.6 (± 8.4) and median iFR was 0.83 (IQR 0.74-0.87). After performing propensity score matching analysis, 48 patients treated with CABG were matched to those who underwent PCI. At a median follow-up period of 2.8 years, the primary endpoint occurred in 8.3% in PCI group and 20.8% in CABG group, respectively (HR 3.80; 95% CI 1.04-13.9; p = 0.043). There was no difference in each component of the primary event (p > 0.05 for all). Within the present study, iFR-guided PCI was associated with lower cardiovascular events rate in patients with ULMD and intermediate SYNTAX score, as compared to CABG. State-of-the-art PCI vs. CABG for ULMD. Study design and primary endpoint in patients with physiologically significant ULMD. MACE was defined as the composite of all-cause death, non-fatal myocardial infarction, and target lesion revascularization. The blue line denotes the PCI arm, and the red line denotes the CABG arm. PCI was associated with significantly lower risk of MACE than CABG. CABG: coronary artery bypass grafting; iFR: instantaneous wave-free ratio; MACE: major adverse cardiovascular events; PCI: percutaneous coronary intervention; ULMD: unprotected left main coronary artery disease.

Deferred Versus Performed Revascularization for Left Main Coronary Disease With Hemodynamic Significance.

BACKGROUND: The majority of randomized controlled trials of revascularization decision-making excludes left main coronary artery disease (LMD). Therefore, contemporary clinical outcomes of patients with stable coronary artery disease and LMD with proven ischemia remain poorly understood. The aim of this study was to assess the long-term clinical outcomes of physiologically significant LMD according to the treatment strategies of revascularization versus revascularization deferral. METHODS: In this international multicenter registry of stable LMD interrogated with the instantaneous wave-free ratio, patients with physiologically significant ischemia (instantaneous wave-free ratio ≤0.89) were analyzed according to the coronary revascularization (n=151) versus revascularization deferral (n=74). Propensity score matching was performed to adjust for baseline clinical characteristics. The primary end point was a composite of death, nonfatal myocardial infarction, and ischemia-driven target lesion revascularization of left main stem. The secondary end points were as follows: cardiac death or spontaneous LMD-related myocardial infarction; and ischemia-driven target lesion revascularization of left main stem. RESULTS: At a median follow-up period of 2.8 years, the primary end point occurred in 11 patients (14.9%) in the revascularized group and 21 patients (28.4%) in the deferred group (hazard ratio, 0.42 [95% CI, 0.20-0.89]; P=0.023). For the secondary end points, cardiac death or LMD-related myocardial infarction occurred significantly less frequently in the revascularized group (0.0% versus 8.1%; P=0.004). The rate of ischemia-driven target lesion revascularization of left main stem was also significantly lower in the revascularized group (5.4% versus 17.6%; hazard ratio, 0.20 [95% CI, 0.056-0.70]; P=0.012). CONCLUSIONS: In patients who underwent revascularization for stable coronary artery disease and physiologically significant LMD determined by instantaneous wave-free ratio, the long-term clinical outcomes were significantly improved as compared with those in whom revascularization was deferred.