The future of interventional cardiology

According to data from the National Statistics Institute, life expectancy has increased from 73.5 years in 1975 to 83.6 years in Spain in the year 2019. Also, the mean age of the population has gone up 10 years during this same period.1 In this sense, the results from the study conducted by Dégano et al.2 in 2013 come as no surprise. They already anticipated a strong increase in the rate of acute coronary syndrome (ACS) within the next 35 years when the Spanish population > 75 years will represent almost a quarter of the national census. This study anticipated that between 2013 and 2049, the cases of ACS in elderly patients would increase over 70%, but keep a discrete growth in patients under 75 years. These data are but a glimpse of a not so distant future when our patients will be older and their life expectancy longer. Also, the association between aging and comorbidity means that we will have to treat more complex patients.

Elderly patients with comorbidities are misrepresented in clinical trials studying the efficacy of both early invasive strategy for the management of non-ST-segment elevation acute coronary syndrome (NSTEACS) and the most suitable antithrombotic treatment.3 Therefore, despite the fact that clinical practice guidelines recommend early invasive strategy in most patients,4 its generalization to these patients is controversial. It is often decided to individualize the decision-making process by weighing risks and benefits and taking into consideration the treating physician’s perception on the possible complications. Hence, conducting clinical trials focused on this subpopulation as creating large registries representative of the actual clinical practice is of paramount importance.

In an article recently published by Pernias et al.5 on REC: Interventional Cardiology, the authors present a wide registry of elderly patients with NSTEACS conducted thanks to the collaborative work of different cardiology units from several Spanish autonomous communities. With over 7000 patients included, this study evaluated the impact of comorbidities on the indication to perform coronary angiographies. The 6 comorbidities studied (cerebrovascular disease, anemia, kidney disease, peripheral arteriopathy, chronic pulmonary disease, and diabetes mellitus) turned out to be independent predictors of a non-invasive approach. Also, it was confirmed that patients with more comorbidities had lower the chances of undergoing an invasive strategy despite having higher GRACE scores.

The comorbidities reported in this study are associated with a worse prognosis in this clinical setting.6 However, this does not necessarily involve low short-term life expectancy per se. Therefore, given the futility of an eventual revascularization a conservative strategy would not be justified. This clearly shows the need for a proper comprehensive geriatric assessment of these patients, since the accumulation of concomitant comorbidities is often followed by frailty, cognitive impairment, and functional dependency. These variables are key finding out why there is a paradoxically reverse correlation in these patients between the risk of ischemic events and the frequency of performing coronary angiographies. In this sense, we should mention the LONGEVO-SCA, a registry conducted in our setting that studied in detail the impact of frailty and geriatric syndromes on the therapeutic approach and vital prognosis of elderly patients with NSTEACS. Important conclusions can be drawn from this registry, like the negative impact of frailty both on the prognosis of elderly patients with NSTEACS and on the benefits of an invasive strategy.7,8

The usefulness of the invasive strategy in elderly patients is not well established. The randomized clinical trial After Eighty included 457 patients > 80 years with non-ST-elevation acute myocardial infarction (NSTEMI). It confirmed a lower incidence rate of the composite endpoint of death or cardiovascular events at the 1.5-year follow-up with the invasive strategy.9 However, this clinical trial did not consider frailty and included less than 25% of the possible candidates, indicative of bias in favor of elderly patients in better general health conditions and with fewer comorbidities.9 The MOSCA clinical trial10 included 106 elderly patients with NSTEMI and comorbidities. Although there were fewer chances of death or ischemic events in this study at the 3-month follow-up in patients randomized to the invasive strategy, no benefits were seen with this strategy at the end of the follow-up (2.5 years).

Currently underway, the MOSCAFRAIL clinical trial11 will assess the efficacy and safety of the invasive strategy and its prognostic effect within the first year after NSTEMI in elderly patients with confirmed frailty. This trial, that included over 10 tertiary and secondary Spanish hospitals, is a systematic geriatric and comorbidity study conducted with widely validated scales. Its results should provide valuable information and greatly impact clinical practice in the coming future.

Another controversial issue with studies of elderly patients with ACS is what clinical outcomes should be assessed. Most randomized and observational studies focus on “traditional” clinical outcomes like mortality or ischemic events. However, on many occasions there are no data on the impact on symptoms, perceived quality of life, and need for readmission, which may indicate better the clinical benefits of this population. In this sense, we should mention the After Eighty clinical trial found no differences regarding quality of life between patients treated with the invasive strategy and those treated conservatively.12

In conclusion, elderly patients with high comorbidities who are hospitalized due to NSTEACS are a common problem today and will remain so in the future. Given the scarce scientific evidence on the therapeutic approach of these patients, studies like the one conducted by Pernias et al.5 improve our understanding of this complicated clinical scenario and remind us of the importance of collaborative research to conduct large registries that show the reality of this emerging problem in our setting.

FUNDING

No funding was received for this work.

CONFLICTS OF INTEREST

None reported.

REFERENCES

During the second half of 2019, cangrelor started selling in our country, a “new” antiplatelet drug with especial pharmacological properties that make it especially appealing for the management of certain clinical situations in the percutaneous coronary intervention (PCI) setting. The adjective “new” is in quotation marks because the clinical trial conducted proved its superiority compared to clopidogrel with ICP. The CHAMPION PHOENIX trial1 was published in 2013 and it was approved by regulatory authorities back in 2015. This delay has probably caused the scientific evidence to lose relevance and, in consequence this drug might not be widely accepted within the cardiology community. Also, the indication specified in the technical label is only based on the conditions of the clinical trial that prompted its approval—which is mandatory—not on real-world practices. This may be confusing when selecting those patients who may benefit from this drug.2

In short, cangrelor is an intravenous reversible, high-affinity antagonist of the platelet P2Y₁₂ receptor of adenosine diphosphate to which it binds directly (without need for conversion into an active metabolite). In pharmacodynamic terms, the properties of cangrelor are: a) rapid onset of action (3 to 6 minutes); b) powerful dose-dependent effect (inhibition > 90% of the P2Y₁₂ receptor signaling pathway) in relation to the dose used in the PCI; and c) rapid offset of action (shot half-life of 3 to 5 minutes) with recovery of the baseline platelet function in 60 to 90 minutes after infusion.3

Given its pharmacological properties, cangrelor may help solve some of the problems posed by other antiplatelet agents. For example, oral P2Y₁₂ receptor inhibitors (iP2Y₁₂), especially clopidogrel and to a lesser extent prasugrel and ticagrelor, have a delayed optimal platelet inhibition, which is even more significant in the ST-segment elevation myocardial infarction (STEMI) setting, where the bioavailability of oral drugs may be compromised (worse intestinal absorption, vomiting, use of opioids or situations like intubation, therapeutic hypothermia or cardiogenic shock).3,4 Also, despite their efficacy in reducing thrombotic events, the use of parenteral glycoprotein IIb/IIIa inhibitors, may be associated with a higher risk of bleeding.

The clinical development of cangrelor as a coadjuvant therapy in the PCI setting is based on the CHAMPION program, in which the first 2 studies conducted (CHAMPION PCI5 and CHAMPION PLATFORM6) were prematurely interrupted due to their futility, in part attributed to a restrictive definition of myocardial infarction.3,7 On the contrary, the CHAMPION PHOENIX clinical trial did prove the superiority of cangrelor vs clopidogrel reducing the main variable of efficacy (a composite of death, myocardial infarction, ischemia guided revascularization or stent thrombosis) after 48 hours in patients who underwent PCI to treat stable angina or any type of acute coronary syndrome (ACS) and who were not eligible for oral iP2Y₁₂ pretreatment.1 We should mention that in a combined analysis of the 3 trials, cangrelor was associated with a slightly higher risk of bleeding mainly at the cost of minor bleeding;8 this good safety profile is probably due to the fact that the drug is administered over a very limited span of time and its effect rapidly goes away after infusion.

The CHAMPION PHOENIX trial has received 2 important criticisms that may condition its implementation in our routine clinical practice. The first is that cangrelor was never compared to prasugrel or ticagrelor (more powerful and effective than clopidogrel and drugs of choice in patients with ACS). The second is that iP2Y₁₂ pretreatment before the PCI was considered an exclusion criterion. We should remember that, although there are serious doubts about its pretreatment benefit in the ACS setting, especially in the non-ST-segment elevation acute coronary syndrome setting,9 this strategy is widely used in our country. As a matter of fact, the European technical label of this drug specifically says that cangrelor is indicated in association with acetylsalicylic acid in patients “who undergo PCI and have not received an oral P2Y₁₂ inhibitor before the PCI, and in whom oral treatment with P2Y₁₂ inhibitors is not possible or desired”.2 Still, the pharmacological properties of cangrelor make it especially interesting in situations where not only the aforementioned pretreatment has not occurred, but also in circumstances where it is considered insufficient. Proof of this is the experience published from the Swedish national registry (SCAAR) during the first 2 years of drug use that found an almost exclusive use of cangrelor in patients with STEMI who underwent primary percutaneous coronary intervention; in this real-world study, cangrelor was combined with ticagrelor mainly, although the latter had already been administered in over 50% of the times in the prehospital setting, which is why in such cases the use of cangrelor would be considered an off-label indication.10

The clinical settings where, in our opinion, cangrelor can be useful both in the PCI setting (most of the cases) and in other situations are shown on figure 1. The most relevant setting would be the primary percutaneous coronary intervention in the management of STEMI, where its use is appropriate in the absence of proper pretreatment with iP2Y₁₂ due to the impossibility or difficulty administering oral drugs (intubation or incoercible vomiting); it may also be considered if the loading dose of iP2Y₁₂ is ineffective during the procedure (short span of time elapsed from its administration until the PCI is performed). Another acceptable situation (much less common than the latter) would be non-emergent high-risk PCIs (such as bifurcations using the dual stent technique, multivessel interventions, in the presence of great thrombotic load, etc.) in patients without iP2Y₁₂ pretreatment. In any case, the drug potential benefit should always be weighed to prevent intraprocedural thrombotic events associated with the procedure and the patient’s bleeding risk. Also, we should remember that the use of cangrelor is ill-advised if glycoprotein IIb/IIIa inhibitors are going to be administered.

Figure 1. Potential favorable clinical settings for the use of cangrelor. ACS, acute coronary syndrome; CCS, chronic coronary syndrome; DAPT, dual antiplatelet therapy; iP2Y₁₂, platelet P2Y₁₂ receptor inhibitors; PCI, percutaneous coronary intervention; STEMI, ST-segment-elevation acute myocardial infarction.

a) The dose in the percutaneous coronary intervention setting should be 30 µg/kg in bolus followed by an infusion at rate of 4 µg/kg/min.

b) The dose studied in the bridging therapy is an infusion of 0.75 µg/kg/min.

Other relevant aspects are the duration of infusion that can be reasonably maintained for at least 2 hours after the PCI. According to the drug technical label, it should be started before the procedure and the infusion lasting at least 2 hours or for as long as the pro- cedure lasts, which ever is longer. Still, this may not be enough in situations where the oral drugs early action is delayed. Also, special care is needed when transitioning to oral drugs; in general, the recommendation here is that ticagrelor can be administered at all times (before, during or after infusion) while thienopyridines can be prescribed after infusion (to avoid an interaction that would imply a time lapse without the proper antiplatelet therapy).3

Taking all this into consideration, cangrelor should be primarily used in the cath lab in situations of periprocedural high thrombotic risk when oral iP2Y₁₂ pretreatment has not occurred, is ill-advised or insufficient. The availability of the drug will probably not change our antiplatelet strategy radically in the short term in the PCI setting. However, in some situations (especially primary percutaneous coronary interventions) its particular pharmacological profile will be very useful. Therefore, its use will probably grow in the interventional cardiology community as we become more familiar with it. In conclusion, cangrelor is an interesting addition to our therapeutic armamentarium in the PCI setting because it can individualize and, therefore, optimize our antithrombotic strategy.

CONFLICTS OF INTEREST

J.L. Ferreiro has declared he has received funds for his lectures for Eli Lilly Co., Daiichi Sankyo, Inc., AstraZeneca, Roche Diagnostics, Pfizer, Abbott, Boehringer Ingelheim, Bristol-Myers Squibb, and Ferrer; also, he has received funds for his counselling for AstraZeneca, Eli Lilly Co., Ferrer, Boston Scientific, Pfizer, Boehringer Ingelheim, Daiichi Sankyo, Inc., Bristol-Myers Squibb; he has also receive research grants from AstraZeneca. J.A. Gómez-Hospital has declared he has received funds for his counselling for Abbott, Medtronic, Boston Scientific, Terumo, and IHT.

REFERENCES

The introduction of endomyocardial biopsy (EMB) for the diagnosis of rejection back in 19721 was considered one of the main advances in the history of heart transplant (HT). Ever since, the EMB has been the gold standard for the diagnosis of rejection. However, this is a repetitive, invasive procedure, often described as uncomfortable by patients and associated with sometimes, serious complications. In this context, in a recent article published on REC: Interventional Cardiology, Tamargo et al.2 shared their combined experience from 2 large national HT centers with the use of EMB via brachial access, a route that is relatively less invasive compared to the femoral access or the most common jugular vein. The authors prove that this is a feasible alternative in 94% of the attempts. Brachial access is safer because it is not associated with some of the major complications of central venous access (mainly pneumothorax and arterial puncture). However, brachial access does not affect the main complication of EMB in the mid-long term: traumatic tricuspid regurgitation occurring after repeated biopsies that can be serious and symptomatic enough to require surgical correction.3 Although brachial access does not reduce procedure time and fluoroscopy time is longer compared to jugular access, it seems evident that this access appears to be more comfortable for patients (although this is based on the testimony of only 19 patients as the authors admit in the limitations section). Therefore, the procedure described is especially appropriate for patients with HT, who represent the largest part of their series and in whom the repeated use of follow-up EMBs is widely accepted as a screening method for graft rejection.

In any case, we should mention that although the EMB still keeps its aura as the gold standard for the diagnosis of rejection, the lack of scientific evidence on this regard is astonishing. In the current era of evidence-based medicine and despite the fact that we have been using this technique for the last 30 years, there is no solid scientific evidence establishing its actual role in the management of patients. In the International Society for Heart and Lung Transplantation clinical practice guidelines,4 systematic EMB for the detection of rejection has a weak recommendation (level IIa) with the lowest possible level of evidence (class C) and with no back up from scientific references.

Also, the histological interpretation of an EMB is rather subjective, the diagnostic criteria have been changed several times, and there is an alarming inter-observer variability.5^,6 Actually, its sensitivity and specificity are completely unknown. On the other hand, all HT groups have experienced the frustration of obtaining repeated false positives7 and false negatives8 to the point that there is often little correlation between the anatomopathological degree of rejection and the functional situation of patient and graft.

Therefore, we are not surprised by the numerous attempts to replace EMB with other non-invasive techniques, mainly echocardiographic. Results have been widely variable and they have never been implemented in the real clinical practice.9 Over the last few years, sophisticated techniques like gene expression profiles have been introduced. However, they have only been applied to selected patients (low risk of rejection) and relatively late after the HT (> 2 months to 6 months), which in practice excludes most clinically relevant rejection episodes.10^,11

The main problem of these attempts to replace EMB with non-invasive techniques is that we are comparing these new diagnostic approaches to EMB assuming that EMB is the gold standard. However, this argument is wrong from the beginning because this supposed gold standard is not such. To consider the EMB as the gold standard, the current standards of evidence-based medicine should be applied to undisputedly show that the current practice of systematic follow-up with periodic EMBs and histology-based treatment does actually improves clinical results.

In this context and given the uncertainties due to the frequent false positives and negatives obtained by the EMB, back in the 1990s here at Hospital Universitario Marqués de Valdecilla we developed a periodic clinical-echocardiographic follow-up strategy without performing mandatory EMBs.12 Our strategy is based on this idea: as time goes by after the HT, the episodes of rejection are less aggressive and more spaced-out. Many subside spontaneously, but others may progress until they compromise the function of the graft and are detected either clinically or on the echocardiography. Although we lose diagnostic sensitivity, with this strategy we achieve great clinical specificity because we are only identifying episodes of rejection that do not subside spontaneously (a minority according to experience) and that often respond well to treatment (figure 1).

Figure 1. Graphic representation of the natural evolution of rejection within the first year after a heart transplant. The episodes of rejection are less intense and frequent across time. The dotted white arrows indicate spontaneous resolution of rejection thanks to baseline immunosuppression. The dotted red arrows indicate the continuous evolution of rejection.

Therefore, in these periodic reviews we conduct clinical assessments and obtain follow-up echocardiograms without mandatory EMBs that are only performed in suspected cases. Since we are looking for specificity, we only assess “hard” echocardiographic endpoints (relevant changes in wall thickness or a reduced ejection fraction) suggestive of rejection that warrant treatment. We decide not to use other techniques like strain, which is much more sensitive and would make us lose specificity.

After a 30-year experience and some 600 HTs performed, the use of EMB is marginal in our program.13 The historic mean is 1.24 EMBs per patient, but over the last 10 years it has gone down to only 0.2. In our routine clinical practice we do not perform any EMBs at 1-year follow-up in most patients. Our confidence in this strategy is based on the clinical results that hold a favorable comparison to those of the Spanish Heart Transplant Registry14 both in the mid and long term. If we exclude the first week after the HT (a time when EMBs are rarely performed), the actual survival rate of Hospital Universitario Marqués de Valdecilla is 85% at 1-year follow-up, 75% at 5-year follow-up, and 61% at 10-year follow-up, which is slightly higher compared to that of the Spanish Heart Transplant Registry14 (84% at 1-year follow-up, 73% at 5-year follow-up, and 58% at 10-year follow-up).

In any case, the brachial vein access suggested by Tamargo et al.2 is a warmly welcomed proposal, especially by the patients. Following the classic Stanford Protocol15 a minimum of 14 EMBs should be performed per patient within the first year. This means that the better tolerance shown to this procedure, which is associated with fewer acute complications, can be very relevant for patients given the large number of biopsies they will need to undergo during follow-up.

Several aspects of the current HT management are based on expert opinions and clinical inertia rather than on scientific evidence. Among them, the myth that the EMB is the gold standard should not be accepted given the lack of evidence supporting it. We believe it is important to move forward in this field, but to do so non-invasive alternatives to EMB should change their current approach. Instead of comparing their diagnostic capabilities to those of the EMB (wrong gold standard), they should rather be based on comparing clinical results, which is ultimately what matters. Therefore, we believe that the time has come to design randomized clinical trials comparing clinical results among the different strategies to reduce the use of EMB based on non-invasive methods and review the traditional rule of performing mandatory EMBs.

CONFLICTS OF INTEREST

None reported.

REFERENCES

Over the last decade, understanding of spontaneous coronary artery dissection (SCAD) has progressed from a condition once considered very rare and the subject largely of esoteric case reports to a disease now recognised as a significant cause of acute coronary syndromes, predominantly in young to middle-aged women. Large observational series have been presented, led by groups in the Mayo Clinic, United States and Vancouver, Canada.1^-3 This increased understanding has led to the publication of consensus documents on best practice in both the US and Europe.4^,5 Despite this, SCAD remains a condition devoid of randomised clinical trial data and debate continues over many aspects of what constitutes optimal management.

In a recent article published in REC: Interventional Cardiology, Bastante et al.6 present data on a highly characterised series from a Spanish centre at the forefront of the progressive management of this condition. Their data provide supporting evidence on findings of direct clinical relevance to contemporary clinical practice and provides novel insight, particularly into the relative merits of antiplatelet therapies for this condition.

The Yip-Saw angiographic classification for SCAD7 coupled with an increased recognition of the central role of intracoronary imaging to aid diagnosis where there is uncertainty, particularly with optical coherence tomography,8 has greatly enhanced the accurate diagnosis of SCAD in the cardiac catheterisation laboratory. In common with other more contemporary and prospective series where there is likely to be less selection bias,2^,9 Bastante et al. report SCAD occurring in an older (median age 56), predominantly peri- and post-menopausal female population with a risk factor profile more akin to an age matched general population (48% current or ex-smoker, 36% hypertension, 42% hypercholesterolaemia).6 This further debunks an oft-repeated mantra that SCAD is a disease of pre-menopausal women with few conventional risk factors for ischaemic heart disease. In this and some other studies, only diabetes (6%) seems less prevalent than in the general population. It is interesting to speculate as to whether the adverse vascular effects of diabetes may paradoxically protect against SCAD. Most importantly however, these data remind clinicians not to restrict their consideration of the diagnosis of SCAD to low risk pre-menopausal females.

Accurate diagnosis is the key first management step for SCAD. This paper gives important insights into the diagnostic role of computed tomography coronary angiography (CTCA). It demonstrates that even in a context where the site of SCAD is known from invasive angiography, conventional CTCA missed more than 20% of SCAD locations. This finding confirms that although CTCA is a tempting non-invasive substitute for angiography (particularly given the known increased risk of iatrogenic dissection during invasive angiography in this population10), this approach should not be used for the primary diagnosis of SCAD. The inadequate sensitivity and specificity of CTCA for this diagnosis likely arises because SCAD has a predilection for the mid-distal coronary arteries (76% of cases in this series) where coronary diameters approach the effective spatial resolution of current CTCA technologies. Whether CTCA could still be useful in specific clinical contexts, for example to exclude or to follow progression of high-risk proximal-to-mid vessel dissections, remains to be elucidated.

A key difference between the management of SCAD and atherosclerotic acute coronary syndromes is the increased risk of complications during percutaneous coronary intervention following SCAD. This, coupled with high reported rates of complete healing in conservatively managed SCAD has led to a consensus favouring a non-interventional strategy where possible.4,5 This approach is further supported by the recent demonstration of relatively small infarct sizes in most convalescent SCAD-survivors assessed by cardiac magnetic resonance imaging, with larger infarcts predicted by ST-segment elevation myocardial infarction presentation, reduced TIMI flow and more proximal or extensive dissections.11 In the paper by Bastante et al. 82% of patients were managed conservatively.6 This is in keeping with a large recent prospective Canadian series and suggests that in experienced centres, most SCAD can be managed without percutaneous coronary intervention.2

Optimal medical management following diagnosis remains unclear. This becomes particularly relevant when considering the optimal long-term antiplatelet treatment strategy after SCAD. Antiplatelet therapies have become a mainstay of treatment for atherosclerotic acute coronary syndromes which are characterised by the formation of luminal thrombus on ruptured or eroded atherosclerotic plaque. However, this paper confirms previous findings12 that the burden of true luminal thrombus in SCAD is low, leading the authors to adopt a clinical strategy of early aspirin monotherapy in conservatively managed SCAD (only 7/27 such patients were managed with dual antiplatelet therapy). The longer-term justification for maintenance aspirin has also been questioned as it appears somewhat counter-intuitive to use a medication that prolongs bleeding time as prophylaxis for a condition whose primary pathophysiological event seems to be the development of a spontaneous intramural haematoma. The only potentially informative clinical data come from a single Canadian observational series and found no definitive benefit or harm.1 However, these findings have not yet been validated in other series and whilst this report from Bastante et al.6 will add further fuel to this debate, clinical trial data are urgently needed to address this question.13

The recognition of extra-coronary arteriopathies in SCAD patients14 has led to a consensus favouring arterial screening by brain to pelvis imaging in all SCAD-survivors.4^,5 However, it is important to demonstrate that imaging has the potential to alter clinical management or prevent vascular events, especially given the associated X-ray dose if computed tomography arteriography is used.

This is particularly relevant as the most frequent arteriopathy in SCAD survivors is fibromuscular dysplasia which although common, seems of little clinical consequence in most cases. Therefore, the report by Bastante et al.6 of 3 patients in whom intra-cerebral aneurysms identified during screening required closure provides some additional much-needed supportive data that at minimum intracerebral arterial imaging is indeed merited in SCAD-survivors.

Finally and most importantly for patients, Bastante et al. complement data from other series suggesting that although major adverse cardiovascular events (18%) and SCAD recurrence (12%) are significant problems for SCAD-survivors, the disease-related mortality following SCAD is very low.6 Prevention of SCAD recurrence is therefore the key target for clinical trials targeting improved outcomes in SCAD.

In summary, there has been a paradigm shift in our knowledge of SCAD leading to improved diagnostic accuracy and increasing adoption of a conservative revascularisation strategy (figure 1). However, key questions remain about optimal long-term medical prophylaxis and the best approach to follow-up imaging. International collaboration will be key to generating the data required to definitively address these questions and ensure we continue to improve our approach to the management of this important condition. Recruitment of patients to the new European Society of Cardiology EURObservational Research Programme SCAD registry (CPMS No. 44577, IRAS No. 270314)15 will provide a key platform for future research.

Figure 1. Schematic of current optimal management approach to spontaneous coronary artery dissection (SCAD). Invasive coronary angiography supported by intracoronary imaging if needed remains the diagnostic gold-standard. A conservative approach to revascularisation is favoured except in more extreme presentations. Screening for remote arteriopathies is recommended but the optimal imaging modality and the role of computed tomography coronary angiography remain unclear. Optimal medical management is unknown. All images are from patients from the UK SCAD study (ISRCTN42661582; REC14/EM/0056). ACE/ARB, angiotensin converting enzyme inhibitors or angiotensin receptor antagonists; CTA, computed tomography arteriography; CTCA, computed tomography coronary angiography; DAPT, dual antiplatelet therapy; ESC-EORP, European Society of Cardiology European Observational Research Programme; FL, false lumen; HTN, hypertension; IVUS, intravascular ultrasound; MRA, magnetic resonance angiography; OCT, optical coherence tomography; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction; TIMI, Thrombolysis in Myocardial Infarction; TL, true lumen.

CONFLICTS OF INTEREST

D. Adlam has received research funds and in kind support from AstraZeneca, including for spontaneous coronary artery dissection research. He has also received an educational grant from Abbott Vascular to support a clinical research fellow and has conducted consultancy for General Electric, Inc. to support research funds. D. Kotecha has no conflicts of interest to declare.

REFERENCES