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This thesis sought evidence from coronary physiology that selected patients with a left main coronary artery (LM) lesion or a chronic total occlusion (CTO) of a coronary artery may benefit from myocardial revascularization (MR) and that physiological assessments may assist in guiding and/or optimizing treatment. In the first part, we investigated the subset of patients with a LM lesion. We first showed by analyzing the nationwide Quality-oriented Electronic Registration of Medical Implant Devices (QERMID) registry data, that patients undergoing LM percutaneous coronary intervention (PCI) had a significant risk of short- and long-term mortality. ST-elevation myocardial infarction (STEMI) patients presenting in cardiogenic shock and undergoing LM PCI also had a higher mortality compared to that in the whole group of cardiogenic shock patients. Second, we reviewed the current evidence on physiology-based revascularization of LM lesions. We concluded that the recommended physiological assessment techniques, fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR), have only been studied relatively limitedly in the setting of LM disease and are probably insufficient on their own to correctly predict the prognosis of the individual patient. Third, we presented the first results of the Prospective Left Main Physiology (PHYNAL) registry that was established to collect more physiological, imaging and outcome data on this type of patients. Physiological measurements yielded contradictory results in more than a quarter of patients and even more so if concomitant downstream disease is present. In the second part, we investigated the subset of patients with a CTO. First, we looked at the evidence underlying CTO PCI. Most proven today is its potential to better reduce ischemic symptoms compared to optimal medical treatment alone. Next, we showed our analysis of the Belgian Working Group on CTO (BWGCTO) registry, illustrating that today CTO PCI can be performed with a high success rate and few complications. Finally, we presented the DISTAL CTO study results. We were able to demonstrate with physiological assessments that CTO patients do indeed have ischemic myocardium and that PCI can alleviate this, which may explain symptomatic improvement. We also showed that residual ischemia can persist in up to 30% of patients. To improve the clinical outcomes of CTO PCI, one should strive to optimize PCI results as best as possible, and our findings suggest that physiological assessment can help with that.

Background. The study aims to assess real-life short- and long-term outcomes of patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) complicated with cardiogenic shock (CS). Outcome after left main (LM) PCI is of particular interest. Methods. Procedural, 30-day, and >30-day mortality rates were assessed in 2744 CS-STEMI patients enrolled between 2012 and 2019 in a nationwide registry involving 49 centers. Results. Procedural, 30-day, and >30-day mortality rates were 6.9%, 39.8%, and 12.6%, respectively. The mortality rates were significantly higher in the 348 patients (12.7%) who underwent LM-PCI (13.5%, 59.5%, and 18.4%, respectively). LM-PCI, a suboptimal PCI result, and transfemoral access were independent predictors of procedural and 30-day mortality. Operator experience was an independent predictor of procedural mortality, but not 30-day mortality. Conclusions. Mortality remains high in CS-STEMI patients, especially within the first month. Patients undergoing LM-PCI are particularly at risk. Operator experience is predictive of procedural mortality.

It is of critical importance to correctly assess the significance of a left main lesion. Underestimation of significance beholds the risk of inappropriate deferral of revascularization, whereas overestimation may trigger major but unnecessary interventions. This article addresses the invasive physiological assessment of left main disease and its role in deciding upon revascularization. It mainly focuses on the available evidence for fractional flow reserve and instantaneous wave-free ratio, their interpretation, and limitations. We also discuss alternative invasive physiological indices and imaging, as well as the link between physiology, ischemia, and prognosis.

Background: Important developments in materials, devices, and techniques have improved outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI), and resulted in a growing interest in CTO-PCI. The Belgian Working Group on Chronic Total Occlusions (BWGCTO) working group aims to assess the evolution within the CTO-PCI landscape over the next years. Methods: From May 2016 onwards, patients undergoing CTO-PCI were included in the BWGCTO registry by 15 centres in Belgium and Luxemburg. Baseline, angiographic, and procedural data were collected. Here, we report on the one-year in-hospital outcomes. Results: Over the course of one year, 411 procedures in 388 patients were included with a mean age of 64 ± 11 years. The majority were male (81%). Relatively complex CTOs were treated (Japanese CTO score =2.2 ± 1.2) with a high procedure success rate (82%). Patient- and lesion-wise success rates were 83 and 85%, respectively. Major adverse in-hospital events were acceptably low (3.4%). Antegrade wire escalation technique was applied most frequently (82%). On the other hand, antegrade dissection and re-entry and retrograde strategies were more frequently applied in higher volume centres and successful for lesions with higher complexity. Conclusion: Satisfactory procedural outcomes and a low rate of adverse events were obtained in a complex CTO population, treated by operators with variable experience levels. Antegrade wire escalation was the preferred strategy, regardless of operator volume.

OBJECTIVES: Percutaneous coronary intervention (PCI) of chronic total occlusion (CTO) has historically been associated with higher event rates during follow-up. The hybrid algorithm and contemporary wiring and dissection re-entry (DR) techniques can potentially improve long-term outcomes after CTO-PCI. This study assessed the long-term clinical outcomes of the hybrid CTO practice, when applied by operators with varying experience levels.METHODS: We examined the 1-year clinical events after hospital discharge of the RECHARGE population, according to technical outcome and final technique. The primary endpoint was major adverse cardiac event (MACE) rate. Centers that provided ≥90% complete 12-month follow-up were included.RESULTS: Follow-up data of 1067 out of 1165 patients (92%) were provided by 13 centers. Mean follow-up duration was 362.8 ± 0.9 days. One-year MACE-free survival rate was 91.3% (974/1067). MACE included death (1.9%; n = 20), myocardial infarction (1.4%; n = 15), target-vessel failure (5.9%; n = 63), and target-vessel revascularization (TVR) (5.5%; n = 59). Non-TVR was performed in 6.7% (n = 71). MACE was significantly in favor of successful CTO-PCI (8.0% vs 13%; P=.04), even after adjusting for baseline differences (adjusted hazard ratio, 0.59; 95% confidence interval, 0.36-0.98; P=.04). Other events, including individual MACE components, were comparable with respect to technical outcome and final technique (DR vs non-DR techniques).CONCLUSIONS: The use of the hybrid algorithm with contemporary techniques by moderate to highly experienced operators for CTO-PCI is safe and associated with a low 1-year event rate. Successful procedures are associated with a better MACE rate. DR techniques can be used as first-line strategies alongside intimal wiring techniques without compromising clinical outcomes.

Background It is unknown if the severity of left ventricular dysfunction in patients with transient left ventricular ballooning syndrome (TLVBS) adversely affects clinical outcome. Furthermore, it remains unclear if the patterns of ventricular involvement are distinct patterns or if they represent varying stages of ventricular involvement. Methods and results All patients with TLVBS who presented to our hospital from August 1998 to August 2012 were prospectively identified and entered into a clinical database. Available ventriculograms were reviewed, the ejection fraction (EF) calculated and a new severity score of left ventricular (LV) involvement was developed to determine the degree of LV dysfunction. The incidence of in-hospital mortality, cardiogenic shock and major cardiac events (heart failure/pulmonary oedema or major cardiac arrhythmia) was recorded. In total, 145 TLVBS episodes were identified in 139 patients. Age at presentation was 67 +/- 12 years and 89% (n = 123) of patients were female. Patients who developed cardiogenic shock or other acute cardiac events had a worse LVEF compared to those who did not (P

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Background: We sought to describe, for the first time, in detail the time course of electrocardiographic (ECG) changes in transient left ventricular ballooning syndrome (TLVBS) from acute onset until 1 year after presentation. Methods: The serial ECGs of all patients identified with TLVBS who presented to our cardiology department from August 1998 to August 2012 were analyzed, from admission to 1-year follow-up, with respect to time from onset of symptoms. Results: In total, 145 TLVBS episodes were identified in 139 patients. In 53% of patients, ST segment elevation was present in the first 3 h after symptom onset, after which there was a steady decline with complete resolution in all patients by 1 month. The presence of T wave inversion (TWI), with or without ST segment depression, was most prevalent between day 1 (60%) and day 30 (71%) from symptom onset, with 17% of patients still exhibiting TWI after 6 to 12 months. At 1 year, approximately 80% of patients had no significant residual ST-T wavechanges. In 86% of patients, there was prolongation of the corrected QT (QTc) interval in the acute phase, with normalization of all QTc intervals by day 14. Conclusions: During the early phase, ECG mimics acute ST elevation myocardial infarction with initial regional ST segment elevation progressing to T wave inversion with or without ST depression. In the majority of patients, significant QTc interval prolongation occurs in the early phase, normalizing by day 14.

Aims: Tryton side branch (SB) reverse culotte stenting has been employed for the treatment of left main (LM) stem bifurcations in patients at high risk for bypass surgery. The aim of this study was to assess acute angiographic results and six-month clinical outcome after implantation of the Tryton stent in the LM. Methods and results: We studied 52 consecutive patients with LM disease treated in nine European centres. Angiographic and clinical data analysis was performed centrally. Fifty-one of 52 patients (age 68+/-11 yrs, 75% male, 42% unstable angina, SYNTAX score 20 8) were successfully treated with the Tryton stent. Medina class was 1,1,1 in 33 (63%), 1,0,1 in 7(13%), 1,1,0 in 3 (6%), 0,1,1 in 8 (4%) and 0,0,1 in 1 (2%). The Tryton stent on a stepped balloon (diameter 3.5-2.5 mm) was used in 41/51 (80%) of cases. The mean main vessel stent diameter was 3.4+/-0.4 mm with an everolimus-eluting stent employed in 30/51 (59%) of cases. Final kissing balloon dilatation was performed in 48/51 (94%). Acutegain was 1.52+/-0.86 mm in the LM and 0.92+/-0.47 mm in the SB. The angiographic success rate was 100%; the procedural success rate reached 94%. Periprocedural MI occurred in three patients. At six-month follow-up, the TLR rate was 12%, MI 10% and cardiac death 2%. The hierarchical MACE rate at six months was 22%. No cases of definite stent thrombosis occurred. Conclusions: The use of the Tryton stent for treatment of LM bifurcation disease in combination with a conventional drug-eluting stent is feasible and achieves an optimal angiographic result. Safety of the procedure and six-month outcome are acceptable in this high-risk lesion PCI. Further safety and efficacy studies with long-term outcome assessment of this strategy are warranted.

Background Available clinical and angiographic scoring systems fail to predict clinical outcomes in real-world patients undergoing revascularization of the unprotected left main coronary artery (ULMCA). Methods We prospectively assessed major adverse cardiac and cerebrovascular events (MACCE) in a real-world population undergoing percutaneous coronary intervention (PCI) for ULMCA disease. Cumulative risk-adjusted mortality in our patients was compared with expected mortality at 30 days based on logistic EuroSCORE and SYNTAX SCORE. Similarly, we plotted cumulative risk-adjusted MACCE at 1 year based on SYNTAX SCORE. Finally, both scores were combined in 1-year Global Risk Charts, including the use of drug-eluting stents (DES), diabetic status, and several factors precluding coronary surgery. Results Over a 12-year period, 240 patients underwent elective (76%) or urgent (24%) PCI of the ULMCA. Median logistic EuroSCORE and SYNTAX SCORE were 8.7% (3.5; 21) and 23% (14; 31). During the first year of follow-up, 89 patients presented MACCE (37.1%) (46 deaths [19.2%], 18 acute myocardial infarctions [7.5%], 45 revascularizations [18.8%] and 4 strokes [1.7%]). Cumulative risk-adjusted mortality based on individual logistic EuroSCORE and SYNTAX SCORE pointed towards significant overestimation (+19 deaths) and underestimation (-35 deaths) of risk by these respective scoring systems. Similarly, the anatomic SYNTAX SCORE largely underestimated cumulative risk-adjusted MACCE (-60 MACCE). The Global Risk Charts provided a more balanced view on 1-year clinical outcome. Conclusion An integrated risk evaluation combining EuroSCORE, SYNTAX SCORE, diabetic status, stent type and general condition, may predict outcomes more accurately awaiting validation in a larger and multicentre setting.

The implantation of intracoronary stents is currently the standard approach for the treatment of coronary atherosclerotic disease. The widespread adoption of this technology has boosted an intensive research activity in this domain, with continuous improvements in the design of these devices, aiming at reducing problems of restenosis (re-narrowing of the stented segment) and thrombosis (sudden occlusion due to thrombus formation). Recently, a new, light-based intracoronary imaging modality, optical coherence tomography (OCT), was developed and introduced into clinical practice. Due to its very high axial resolution (10-15 mu m), it allows for in vivo evaluation of both stent strut apposition and neointima coverage (a marker of healing of the treated segment). As such, it provides valuable information on proper stent deployment, on the behaviour of different stent types in-vivo and on the effect of new types of stents (e.g. drug-eluting stents) on vessel wall healing. However, the major drawback of the currentOCT methodology is that analysis of these images requires a tremendous amount of-currently manual-post-processing. In this manuscript, an algorithm is presented that allows for fully automated analysis of stent strut apposition and coverage in coronary arteries. The vessel lumen and stent struts are automatically detected and segmented through analysis of the intensity profiles of the A-lines. From these data, apposition and coverage can then be measured automatically. The algorithm was validated using manual assessments by two experienced operators as a reference. High Pearson's correlation coefficients were found (R = 0.96-0.97) between the automated and manual measurements while Bland-Altman analysis showed no significant bias with good limits of agreement. As such, it was shown that the presented algorithm provides a robust and fast tool to automatically estimate apposition and coverage of stent struts in in-vivo OCT pullbacks. This will be important for the integration of this technology in clinical routine and for the analysis of datasets of larger clinical trials.

Objective Patients with lymphoma, lung or breast neoplasia show significant improvement in their disease-specific survival after radiotherapy (RT), but these benefits may be offset by delayed effects of irradiation of the heart. We compared clinical outcome after coronary stenting in patients with neoplastic disease and previous thoracic RT with matched patients without previous RT. Design Single-centre retrospective case-control study. Patients and methods Each patient with former thoracic RT undergoing coronary stenting between June 1998 and June 2005 was matched to two control patients according to several known prognostic factors (gender, age, available follow-up, stented vessel, drug-eluting stent use, unstable coronary disease, renal insufficiency, diabetes, bifurcational disease, stent length and size and ejection fraction). Main outcome measures Major adverse cardiac events (MACE) were defined as the composite of cardiac death, acute myocardial infarction (AMI) and target lesion revascularisation (TLR) and were assessed at latest follow-up and compared using Cox regression analyses. Results 41 patients underwent coronary stenting at 6 +/- 4 years after RT. Clinical outcome at 5 +/- 2 years after stenting was compared with outcome in 82 matched patients. For all-cause mortality, the hazard ratio for RT versus no RT was 4.2 (95% CI 1.8 to 9.5; p=0.0006). For cardiac mortality, the estimated hazard ratio was 4.2 (95% CI 1.0 to 17.0; p=0.0451). No significant differences were detected in terms of AMI, TLR, MACE or stent thrombosis. Conclusions Our findings suggest an increased risk of all-cause and cardiac mortality in patients who underwent coronary stent implantation after previous thoracic RT. Verification in larger patient populations is warranted.