Background: Coronary microvascular dysfunction is a clinically significant component of ischemic heart disease. There can be heterogenous patterns of coronary microvascular dysfunction defined by invasive physiologic indexes such as coronary flow reserve (CFR) and index of microcirculatory resistance (IMR). We sought to compare the prognosis of coronary microvascular dysfunction according to different patterns of CFR and IMR. Methods: The current study included 375 consecutive patients undergoing invasive physiologic assessment for suspected stable ischemic heart disease and intermediate but functionally nonsignificant epicardial stenosis (fractional flow reserve, >0.80). According to cutoff values of invasive physiologic indexes reflecting microcirculatory function (CFR, <2.5; IMR, ≥25), patients were classified into 4 groups: (1) preserved CFR and low IMR (group 1), (2) preserved CFR and elevated IMR (group 2), (3) depressed CFR and low IMR (group 3), and (4) depressed CFR and elevated IMR (group 4). Primary outcome was a composite of cardiovascular death or admission for heart failure during the follow-up time. Results: Cumulative incidence of the primary outcome was significantly different among the 4 groups (group 1, 20.1%; group 2, 18.8%; group 3, 33.9%; and group 4, 45.0%; overall P <0.001). Depressed CFR had significantly higher risk of primary outcome than preserved CFR in both low (hazard ratio [HR], 1.894 [95% CI, 1.112–3.225]; P =0.019) and elevated IMR subgroups (HR, 3.307 [95% CI, 1.519–7.202]; P =0.003). Conversely, the risk of primary outcome was not significantly different between elevated and low IMR in preserved CFR subgroups (HR, 0.926 [95% CI, 0.428–2.005]; P =0.846). Furthermore, as continuous variables, IMR-adjusted CFR (adjusted HR, 0.644 [95% CI, 0.537–0.772]; P <0.001) was significantly associated with the risk of primary outcome but CFR-adjusted IMR (adjusted HR, 1.004 [95% CI, 0.992–1.016]; P =0.515) was not. Conclusions: Among patients with suspected stable ischemic heart disease who were found to have an intermediate but functionally nonsignificant epicardial stenosis, depressed CFR was associated with an increased risk of cardiovascular death and admission for heart failure. However, elevated IMR alone with preserved CFR showed limited prognostic value in this population. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05058833.

Background: Coronary microvascular dysfunction (CMD) has been considered as a possible cause of cardiac diastolic dysfunction. The current study evaluated the association between cardiac diastolic dysfunction and CMD, and their prognostic implications in patients without significant left ventricular systolic dysfunction and epicardial coronary stenosis. Methods and Results: A total of 330 patients without left ventricular systolic dysfunction (ejection fraction ≥50%) and significant epicardial coronary stenosis (fractional flow reserve >0.80) were analyzed. Cardiac diastolic dysfunction was defined by echocardiographic parameters (early diastolic transmitral flow velocity/early diastolic mitral annular velocity, e' velocity, tricuspid regurgitation velocity, and left atrial volume index). Overt CMD was defined as coronary flow reserve <2.0 and index of microcirculatory resistance ≥25 U. The primary end point was cardiovascular death or admission for heart failure during 5 years of follow‐up. In patients without left ventricular systolic dysfunction and significant epicardial coronary stenosis, prevalence of cardiac diastolic dysfunction and overt CMD was 25.5% and 11.2%, respectively. Overt CMD was independently associated with cardiac diastolic dysfunction (adjusted odds ratio, 3.440 [95% CI, 1.599–7.401]; P =0.002). Patients with cardiac diastolic dysfunction showed significantly higher risk of the primary outcome than those without (adjusted hazard ratio [HR], 2.996 [95% CI, 1.888–4.755]; P <0.001). Patients with overt CMD also showed significantly higher risk of the primary outcome than those without (adjusted HR, 2.939 [95% CI, 1.642–5.261]; P <0.001). Presence of overt CMD was associated with significantly increased risk of cardiovascular death among the patients with cardiac diastolic dysfunction (43.8% versus 14.5%; P =0.006) but not in patients without cardiac diastolic dysfunction (interaction P <0.001). Inclusion of overt CMD into the model with cardiac diastolic dysfunction significantly improved predictive ability for cardiovascular death or heart failure admission (conconrdance index, 0.719 versus 0.737; P for comparison=0.034). Conclusions: There was significant association between the presence of cardiac diastolic dysfunction and overt CMD. Both cardiac diastolic dysfunction and overt CMD were associated with increased risk of cardiovascular death or admission for heart failure. Integration of overt CMD into cardiac diastolic dysfunction showed improvement of the risk stratification in patients without significant left ventricular systolic dysfunction and epicardial coronary stenosis. Registration: DIAST‐CMD (Prognostic Impact of Cardiac Diastolic Function and Coronary Microvascular Function) registry; Unique identifier: NCT05058833.

Background: Recently, diastolic stress testing and invasive hemodynamic measurements have been emphasized for diagnosis of heart failure with preserved ejection fraction (HFpEF) because when determined using noninvasive parameters it can fall into a nondiagnostic intermediate range. The current study evaluated the discriminative and prognostic roles of invasive measured left ventricular end‐diastolic pressure in the population with suspected HFpEF, particularly for patients with intermediate Heart Failure Association Pre‐test Assessment, Echocardiography & Natriuretic Peptide, Functional Testing, Final Etiology (HFA‐PEFF) score. Methods and Results: A total of 404 patients with symptoms or signs of HF and preserved left ventricular systolic function were enrolled. All subjects underwent left heart catheterization with left ventricular end‐diastolic pressure measurement for confirmation of HFpEF (≥16 mm Hg). The primary outcome was all‐cause death or readmission due to HF within 10 years. Among the study population, 324 patients (80.2%) were diagnosed as invasively confirmed HFpEF, and 80 patients (19.8%) were as noncardiac dyspnea. The patients with HFpEF showed a significantly higher HFA‐PEFF score than the patients with noncardiac dyspnea (3.8±1.8 versus 2.6±1.5, P <0.001). The discriminative ability of the HFA‐PEFF score for diagnosing HFpEF was modest (area under the curve, 0.70 [95% CI, 0.64–0.75], P <0.001). The HFA‐PEFF score was associated with a significantly higher 10‐year risk of death or HF readmission (per‐1 increase, hazard ratio [HR], 1.603 [95% CI, 1.376–1.868], P <0.001). Among the 226 patients with an intermediate HFA‐PEFF score (2–4), those with invasively confirmed HFpEF had a significantly higher risk of death or HF readmission within 10 years than the patients with noncardiac dyspnea (24.0% versus 6.9%, HR, 3.327 [95% CI, 1.109–16.280], P =0.030). Conclusions: The HFA‐PEFF score is a moderately useful tool for predicting future adverse events in suspected HFpEF, and invasively measured left ventricular end‐diastolic pressure can provide additional information to discriminate patient prognosis, particularly in those with intermediate HFA‐PEFF scores. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04505449.

Background The prognostic value of estimated pulse wave velocity (ePWV) has been infrequently explored in high-risk patient groups. Our study aimed to evaluate the prognostic significance of ePWV among patients undergoing a percutaneous coronary intervention (PCI) with a drug-eluting stent (DES). Methods A total of 4119 consecutive subjects who underwent a PCI with a DES (mean age, 67.1 ± 11.6 years and 33.1% were female) were retrospectively analyzed. ePWV was calculated based on the patient’s age and mean blood pressure. Major adverse cardiovascular events (MACE), including cardiac death, non-fatal myocardial infarction, coronary revascularization, and ischemic stroke, were evaluated. Results During a median follow-up duration of 3.51 years (interquartile range, 1.35–6.37 years), there were 746 MACEs (18.1%). A multivariable analysis showed that a higher ePWV was associated with a higher MACE incidence (middle tertile vs. the lowest tertile: hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.81–3.42; p < 0.001; the highest tertile vs. the lowest tertile: HR, 6.18; 95% CI, 4.33–8.80; p < 0.001) The inclusion of ePWV data significantly increased the global chi-square values when added to the clinical information (from 96 to 128; p < 0.001). Conclusion ePWV demonstrated a significant association with MACEs in patients who underwent DES implantation. Given its relative simplicity to calculate, ePWV could potentially serve as a valuable instrument for stratifying cardiovascular risks within this high-risk patient population.

Kim HL, et al. J Korean Med Sci. 2023 Dec;38:e414. https://doi.org/10.3346/jkms.2023.38.e414

Background: Intracoronary physiologic indexes such as coronary flow reserve (CFR) and left ventricular ejection fraction (LVEF) have been regarded as prognostic indicators in patients with coronary artery disease. The current study evaluated the association between intracoronary physiologic indexes and LVEF and their differential prognostic implications in patients with coronary artery disease. Methods and Results: A total of 1889 patients with 2492 vessels with available CFR and LVEF were selected from an international multicenter prospective registry. Baseline physiologic indexes were measured by thermodilution or Doppler methods and LVEF was recorded at the index procedure. The primary outcome was target vessel failure, which was a composite of cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularization over 5 years of follow‐up. Patients with reduced LVEF <50% (162 patients [8.6%], 202 vessels [8.1%]) showed a similar degree of epicardial coronary artery disease but lower CFR values than those with preserved LVEF (2.4±1.2 versus 2.7±1.2, P <0.001), mainly driven by the increased resting coronary flow. Conversely, hyperemic coronary flow, fractional flow reserve, and the degree of microvascular dysfunction were similar between the 2 groups. Reduced CFR (≤2.0) was seen in 613 patients (32.5%) with 771 vessels (30.9%). Reduced CFR was an independent predictor for target vessel failure (hazard ratio, 2.081 [95% CI, 1.385–3.126], P <0.001), regardless of LVEF. Conclusions: CFR was lower in patients with reduced LVEF because of increased resting coronary flow. Patients with reduced CFR showed a significantly higher risk of target vessel failure than did those with preserved CFR, regardless of LVEF. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04485234.