Coronary perfusion pressure (CPP) is the pressure gradient that drives forward coronary flow for myocardial perfusion (1). Coronary blood largely supplies the myocardium during the diastolic phase of the cardiac cycle (2). In the systolic phase, blood flow can follow the systolic blood pressure (SBP) into the epicardial coronary artery. However, the blood flow supply is obstructed due to myocardium contraction. Conversely, when the myocardium relaxes in the diastolic phase, it experiences pressure from both the aorta and left ventricle, and the coronary flow follows the pressure gradient between the aortic diastolic blood pressure (DBP) and left ventricular end-diastolic pressure (LVEDP) to provide myocardium blood supply. Therefore, CPP is defined as the pressure difference between DBP and LVEDP (3). Both DBP and LVEDP can be used as predictors of clinical outcomes in patients with cardiovascular diseases. Low DBP has been associated with subclinical myocardial ischemia and other unfavourable outcomes (4–6). The LVEDP in patients with left ventricular failure not only has an impact on long-term outcomes, but can also be a surrogate of an unloading mechanical device to increase coronary flow (7–9). However, despite being a composite of DBP and LVEDP, the association between CPP and clinical events in patients with heart diseases remains poorly explored.

In addition to CPP, stenosis of the coronary artery is another mechanical factor associated with myocardial perfusion. In the presence of coronary stenotic lesions, a post-stenotic pressure drop will result in flow-limited myocardial hypoperfusion. Regardless of whether coronary bypass surgery or percutaneous coronary intervention (PCI) is applied, achievement of complete revascularisation (CR) is the primary treatment goal, especially for patients with heart failure or left ventricular systolic dysfunction (LVSD). However, limited by patients' comorbidities, anatomical factors, and technical or procedural considerations, CR is only achieved in less than two-thirds of patients either by PCI or coronary bypass surgery in real-world practise (10–12). Recent studies demonstrate that reasonable incomplete revascularization (RIR) is determined by a reasonable assessment method to decide whether a lesion should be treated, such as fractional flow reserve or residual synergy between percutaneous coronary intervention with Taxus and cardiac surgery (SYNTAX) score (rSS) calculation, is equivalent to CR in terms of long-term outcomes (13, 14). The rSS is a systemic angiographic score that can objectively quantify the reasonableness of RIR. It most generally defines a post revascularization score of 0<rSS≤8 as RIR (15).

Considering that both CPP and residual stenosis of coronary arteries after revascularization are responsible for myocardial perfusion, this study retrospectively analysed a real-world registry data and investigated whether CPP had a risk stratification role in patients with LVSD undergoing PCI with either an angiographic CR or RIR strategy.

There are three main findings in the current study. First, CPP and RIR (0<rSS≤8) were independent predictors of long-term mortality in patients with LVSD. Second, when patients with LVSD had a low CPP ( ≤ 42 mmHg), RIR was worse than CR in long-term survival. Third, RIR could only be comparable to CR in long-term survival when patients had a CPP of >42 mmHg. Therefore, we concluded that CR is crucial for patients with LVSD, whose CPP was ≤ 42 mmHg. The RIR was only equivalent to CR in terms of long-term survival when CPP exceeded 42 mmHg. This is the first study to demonstrate that CPP, measured using an invasive catheter, has a risk stratification role in selecting different revascularization strategies in patients with LVSD.

The CPP is the general presentation of a patient‘s age, comorbidities, and haemodynamic conditions. The interactions between CPP, regulating coronary flow, and heart function are complex and insufficiently understood (16, 17). When the CPP remains between 40 and 120 mmHg, the coronary autoregulation function through microvascular dilation or contraction can modify vascular resistance to maintain a consistent coronary flow (18, 19). If the pressure is below this threshold (about 40 mmHg) and even if the coronary vascular bed seems to be fully dilated, an increase or decrease in coronary flow directly corresponds to a linear increase or decrease in CPP (20, 21). Canty et al. reported that when CPP is <40 mmHg, myocardial wall thickening and segmental shortening will decrease from normal to akinesis (22). Any reduction in resting coronary flow will impact myocardium performance. These results indicate that the myocardium is very sensitive and cannot tolerate resting coronary flow reduction (22, 23). We assumed that CPP will markedly affect the clinical outcomes in patients with LVSD. Therefore, we selected this patient population in this study.

Most previous studies have discussed myocardial perfusion or coronary flow rather than CPP due to intrinsic myocardial autoregulation mechanisms. Johnson et al. investigated 188 patients after 213 revascularizations with either PCI or coronary bypass surgery in a cardiac positron emission tomography database (24). Despite improvements in stress-induced perfusion defects after revascularization, resting myocardial perfusion did not significantly change. They hypothesised that in most patients, autoregulation implies that resting perfusion measurements are of limited value in estimating treatment response. We agree with their hypothesis; however, Johnson's study does not adequately account for patients with extremely low CPP levels. When patients with a low resting CPP, which is below the lower limit of autoregulation threshold, such as those in the lowest tertile (median CPP = 36 mmHg, mean CPP = 34.4 mmHg) of this present study, they are to have a coronary flow far lower than the consistent flow to maintain adequate myocardial perfusion. Even though myocardial perfusion scanning was not performed, patients with LVSD with a low resting CPP should be considered to have insufficient myocardial perfusion and a worse prognosis.

Dr. Böhm et al. demonstrated that lower DBP in patients with stenotic coronary lesions is associated with worse adverse cardiovascular event rates (25). However, after coronary revascularization, the increased risk with low DBP is not observed. Hence, they suggest that DBP potentially involves CPP and myocardial perfusion and is associated with clinical outcomes. However, they do not describe any reperfusion strategy or post-PCI patency of the coronary arteries. The present study emphasises the importance of CR in patients with low CPP. When the CPP is below the threshold to maintain coronary autoregulation function or if the coronary microvascular bed had been maximally dilated, coronary blood flow may begin to decrease when the coronary lesion stenosis exceeds 50% (26). Hence, patients with an extremely low CPP have reduced flow regulation function, and their myocardial perfusion is very sensitive to the patency of coronary arteries. Only performing RIR with 0<rSS≤8 in patients with low CPP may not good enough to improve outcomes. Therefore, CR (rSS = 0) for these patients with low CPP ( ≤ 42 mmHg) is essential.

Pursuing CR in all patients with ischemic heart disease is reasonable and feasible. However, the patient's general condition, comorbidities, or lesion characteristics, such as fragile, heart failure, CKD, acute coronary syndrome presentation, calcified lesions, and chronic total occlusion, may increase the risk of the procedure and limit the benefit and achievement of angiographic CR (27–30). Although the use of mechanical circulation support during non-emergency high-risk PCI can enhance tissue perfusion and achieve higher success rates of angiographic CR, the efficacy of aggressive PCI on improving outcomes is debatable (31, 32). The RIR may have comparable outcomes with angiographic CR in patients undergoing PCI under demanding clinical settings (28, 33). The RIR is indicated in specific clinical situations according to physiological, functional, or anatomic criteria (34). The physiological criteria of RIR include sparing stenotic vessels with fractional flow reserve >0.8, while the functional criteria include sparing stenotic vessels supplying non-viable or small territories of the myocardium. The anatomic criteria include sparing a stenotic lesion that is a non-culprit lesion located at a small vessel or asymptomatic side branch. In general, rSS was an acceptable method to quantify the anatomic definition of RIR. However, the present results challenge this definition. For patients with low CPP ( ≤ 42 mmHg), anatomic rSS criteria (0<rSS≤8) might be insufficient to access the reasonableness of revascularization. Functional or physiological-guided PCI can decrease unnecessary interventions, but previous studies have not considered the impact of low CPP or autoregulation dysfunction on the fractional flow reserve ratio. Further studies are needed to elucidate whether functional or physiological-guided RIR is comparable to angiographic CR in long-term outcomes in patients with low CPP.

Reasonably incomplete revascularization (0<rSS≤8) was known to achieve a comparable outcome and alternative therapy for patients with difficulty achieving CR (rSS = 0) in PCI. This study showed that CPP had a risk stratification role in selecting revascularization strategy in patients with patients with LVSD, as shown in Figure 3. The outcomes of patients with LVSD with CPP > 42 mmHg were consistent with previous studies, showing that RIR was equivalent to CR in long-term mortality. However, when patients with LVSD had CPP ≤ 42 mmHg, RIR was significantly worse than CR in long-term survival. Performing RIR was only inappropriate in patients with LVSD with CPP ≤ 42 mmHg. Additionally, CR should be attempted in this patient subgroup.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by Chang Gung Medical Foundation Institutional Review Board (Approval No. 202101400B0). Written informed consent was not provided because this study analysed medical records retrospectively.

M-JH and I-CH: conceptualisation. M-JH, C-CC, and D-YC: methodology. M-JH, CC-C, D-YC, C-HL, M-YH, J-KY, Y-CH, Y-YL, C-YC, C-YW, S-HC, and I-CH: formal analysis and investigation. M-JH and I-CH: writing review and editing. I-CH: funding acquisition and supervision. All authors contributed to the article and approved the submitted version.

This work was supported by grants from Chang Gung Medical Research Program (Grant Numbers CORPG 3C0162).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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