Requirements and sustainability of primary PCI programs in Spain for the management of patients with STEMI. SEC, AEEC, and SEMES consensus document

INTRODUCTION

Coronary vasoreactivity testing performed by intracoronary infusion of acetylcholine is basically used with 2 goals in mind: for endothelial function assessment and as a vasospasm provocation test in clinically suspicious cases. Although these tests have been known and used for decades, its use is not yet fully consolidated in our setting. This is mainly due to a scarce suspicion of myocardial ischemia due to micro or vasomotor disorders that has eventually lowered the demand for these tests. In addition, the lack of test standardization and training, the off-label use of acetylcholine, and the doubts surrounding these tests safety profile have not encouraged their widespread use in the routine clinical practice.

Over the last few years, this scenario has changed dramatically thanks to the growing evidence on the importance of diagnosing the causes of myocardial ischemia not directly related to fixed stenoses. Currently, invasive coronary spasm provocation tests are formally recommended by the European Society of Cardiology in its clinical practice guidelines on the management of chronic coronary syndromes, non-ST-segment elevation acute coronary syndromes, and ST-segment elevation acute coronary syndromes.1-3 The most common indications are to treat patients with angina or ischemia but without non-obstructive coronary lesions (ANOCA, INOCA—in this document, both coined under the term INOCA—), myocardial infarction with non-obstructive coronary arteries (MINOCA), persistent angina after coronary revascularization, obstructive coronary artery disease with clinical suspicion of associated angina of microvascular origin, and finally, patients with recovered sudden death of undetermined causes.1-3 Table 1 summarizes all clinical indications and level of recommendation to perform vasospasm provocation testing. Although this paper focuses on coronary vasoreactivity testing, we should remember that its use is often recommended simultaneously with other coronary functional testing performed using pressure guidewires like coronary flow reserve and microcirculation resistance measurements.1-5 The specific diagnosis of functional damage to coronary arteries and its targeted therapies have both improved the quality of life of patients with INOCA.6 The treatment recommended for coronary vasospasm is calcium channel blockers, nitrates, and nicorandil.6,7

Table 1. Clinical indications for the coronary vasospasm provocation test performed by intracoronary infusion of acetylcholine

Class	Indication	Clinical specifications
Class I (highly recommended)	Clinical suspicion of vasospastic angina without objective documentation of ischemia or obstructive coronary artery disease in patient with chronic symptoms	– Vasospastic angina can occur predominantly at rest (35%), during exertion (30%), as a mixed pattern (30%) or dyspnea (5%)4 – The epicardial and microvascular function assessment in maximum hyperemia with a pressure guidewire is advised
	Acute coronary syndrome without presence of culprit lesions on the coronary angiography	– Carefully review the angiography to discard embolisms and radiolucent images consistent with thrombus or coronary dissections – The use of intravascular imaging (intracoronary ultrasound or optical coherence tomography) for this type of lesions is advised – Exclude other causes for high troponin levels (like myocarditis) through segmental assessments (ventriculography or echocardiography) and magnetic resonance imaging
	Recovered inexplicable sudden death	– After excluding structural and/or arrhythmic heart disease
	Study of syncope preceded by thoracic pain	– After excluding structural and/or arrhythmic heart disease
	Recurrent angina despite revascularization	– First assess the pressure guidewire to exclude epicardial functional disease and microcirculation disorders in maximum hyperemia
Class IIa (recommended)	Clinically documented vasospastic angina in a spontaneous event or on the non-invasive provocation test that is unresponsive to medical therapy	– Patients unresponsive to therapy with calcium channel blockers and nitrates or nicorandil – Epicardial and microvascular function assessment in maximum hyperemia with a pressure guidewire is advised
Class IIb (debatable)	Clinically documented vasospastic angina or on the non-invasive provocation test that responds to medical therapy to know the type and degree of vasospasm	– The specification of the macro/microvascular spasm and whether it causes the occlusion of the artery can be relevant for the patient’s prognosis – Epicardial and microvascular function assessment in maximum hyperemia with a pressure guidewire is advised
Class III (ill-advised)	Asymptomatic patients	Asymptomatic patients
	Patients with ejection fractions < 35%	Patients with ejection fractions < 35%
	Significant epicardial coronary artery disease (left main coronary artery and/or 3 vessels)	Significant epicardial coronary artery disease (left main coronary artery and/or 3 vessels)
	Adapted with permission from the consensus document elaborated by the COVADIS Working Group (Coronary Vasomotion Disorders International Study).5

Based on the current clinical practice guidelines, the objective of the Working Group on Intracoronary Diagnostic Techniques of the Interventional Cardiology Association of the Spanish Society of Cardiology (ACI-SEC) is to facilitate and standardize the use of coronary vasoreactivity testing. Thus, this paper has been drafted to expose all technical steps in a practical way to encourage the performance and interpretation of these tests in our setting.

NORMAL ENDOTHELIAL FUNCTION OF CORONARY ARTERIES

The modulatory function of vascular endothelium in the blood flow towards the myocardium is intrinsically associated with its metabolic characteristics. Compared to the skeletal muscle, the heart has pretty high oxygen needs (some 20 times higher). The way this oxygen supply is achieved is through very high tissue extraction at baseline: at rest the myocardium extracts approximately 70% to 80% of the oxygen transported by hemoglobin compared to 30% of the skeletal muscle. This explains why, unlike other organs, the mechanism through which the heart regulates oxygen supply to the myocardium changing metabolic needs is fast regulation and constant blood flow into the coronary system.8

Microcirculation (arteries and arterioles < 400 µm) is basically responsible for regulating coronary blood flow. Although regulation is complex and includes metabolites, hormones, neurotransmitters, and other factors, the main protagonist is the vascular endothelium that produces nitric oxide—a powerful vasodilator—in response to different stimuli. Also, other vasodilator factors—like the hyperpolarizing endothelial factor—and vasoconstrictor factors like endothelin. Endothelium-dependent vasodilation can be stimulated through different ways, but the most commonly used one is the infusion of acetylcholine.

In normal conditions, an artery with a healthy endothelium responds to acetylcholine by releasing nitric oxide that translates into vasodilation. In the presence of artery denudation from the endothelium or if the action of the nitric-oxide synthase enzyme is blocked, the artery responds to acetylcholine with vasoconstriction due to the stimulation of smooth muscle muscarinic receptors not counteracted by the nitric oxide of endothelial origin. Therefore, the infusion of acetylcholine can be used to assess endothelial function: if normal, vasodilation becomes evident. If not, vasoconstriction kicks in. The macrovascular compartment endothelial function (epicardial) can be assessed on an angiography. However, to assess the endothelium-dependent response in microcirculation, blood flow should be measured using a Doppler guidewire or thermodilution. From the macrovascular point of view, visually evident epicardial vessel vasoconstriction in response to acetylcholine is considered endothelial dysfunction. Figure 1 shows examples of vasodilation (physiological) and vasoconstriction responses (suggestive of endothelial dysfunction) to the administration of acetylcholine. From the microvascular point of view, flow reductions or increases < 50% in response to the administration of acetylcholine are considered anomalous.9 Figure 2 shows examples of microvascular function assessment using the Doppler technique or intracoronary thermodilution.

Figure 1. Possible results of the vasospasm provocation test with acetylcholine. Case 1: physiological response (vasodilator response to acetylcholine). Case 2: endothelial dysfunction with vasoconstriction with respect to baseline that does not meet the criteria for micro or macrovascular spasm. Case 3: macrovascular spasm with significant vasoconstriction of the left coronary tree. Case 4: microvascular spasm due to moderate vasoconstriction of the left tree meeting the clinical and ECG criteria for ischemia. ACh, acetylcholine; DS, diameter stenosis; NTG, nitroglycerin.

Figure 2. Combined assessment of macro and microvascular function. A: pressure-Doppler guidewire study (Combowire, Philips, The Netherlands). After the angiography and measurement of baseline flow velocity, growing doses of acetylcholine are injected. After the second dose, moderate vasoconstriction of the left anterior descending coronary artery occurs followed by an occlusive spasm at circumflex artery level plus a slower flow velocity in the left anterior descending coronary artery indicative of microvascular vasoconstriction. The spasm is solved with intracoronary nitroglycerin followed by the adenosine non-endothelium-dependent assessment of microvascular function. The patient shows macro and microvascular endothelial dysfunction and a normal non-endothelium-dependent microvascular function. B: macrovascular endothelial function assessment appears normal; adenosine non-endothelium-dependent assessment with thermodilution guidewire (Pressurewire X, Abbott, United States). Coronary flow reserve is 5.9, and the index of microcirculatory resistance is 11, which is suggestive of a normal microvascular function. In conclusion, physiological examination without any relevant findings.

CORONARY VASOSPASM PROVOCATION TESTING

Different stimuli can be used to provoque epicardial or microvascular coronary spasm. Non-pharmacological stimuli like hyperventilation or coming into contact with cold are associated with an excessive number of false negatives for clinical use. Non-invasive coronary vasospasm assessment (based on changes on the ECG or the echocardiography through the IV administration of ergonovine) is associated with a risk of causing nitrate-resistant flow-limiting coronary spasm.4 For this reason, to this date, invasive studies based on the intracoronary administration of drugs are considered the single most sensitive and safe method. Actually, to this date, it is the method recommended by European guidelines and consensus docments.2,7 The direct administration of drugs allows us to use lower doses and establish a time correlation between the development of coronary spasm followed by symptom onset and changes on the ECG. Also, it facilitates immediate treatment through the direct administration of nitrates.4,10 The use of acetylcholine vs ergonovine is advised too since the former acts on a specific pathway (by stimulating cholinergic receptors only), and its safety profile is good because its half-life is shorter. Also, because it responds faster to nitrates in case of vasoconstriction.11 Also, acetylcholine allows us to assess the vascular endothelial response specifically, which is an additional advantage. The studies that compared the results of vasospasm provocation testing with acetylcholine vs ergonovine found similar sensitivity and high matching (94%) between the two. Therefore, in the presence of a negative acetylcholine test no additional studies with different drugs are advised.12

ACETYLCHOLINE

Acetylcholine is a neurotransmitter largely found in the nervous system (central, autonomous, and peripheral). It is used in the neuromuscular junction, in all synapses of the parasympathetic autonomous system, and in the first synapsis of the sympathetic nervous system. The muscarinic receptor of acetylcholine has 5 different subtypes; among them, subtype M2 is largely found in the myocardium where it reduces the heart rate and the cardiac conduction system; subtype M3 is found in the coronary arteries both in the endothelium and the smooth muscle. In the coronary arteries, the M3 receptor stimulates the contraction of the vascular smooth muscle (vasoconstriction). Also, it stimulates the endothelial production of nitric oxide that spreads into the smooth muscle reducing the concentration of calcium, and causing relaxation (vasodilation).13,14 Acetylcholine is rapidly hydrolyzed in both the neuromuscular junction and blood by the action of cholinesterases. When infused intracoronary in the doses described here, no systemic effects occur, and its cardiac effects only last a few minutes.

ACETYLCHOLINE-INDUCED ENDOTHELIAL DYSFUNCTION AND CORONARY VASOSPASM

Endothelial dysfunction is associated with the number of cardiovascular risk factors and is a well-known precursor of atherosclerosis.15 Also, the presence of endothelial dysfunction has been associated with the appearance of ischemia in the ischemia exercise test, heavier calcification and presence of necrotic and lipidic content in the vascular wall, and more cardiovascular adverse events in the long run.16-18 The prevalence of a vasoconstrictor response to the intracoronary infusion of acetylcholine, therefore, similar to an epicardial endothelial dysfunction, is variable depending on the characteristics of the patients being more common among males.19 In the studies conducted in patients with INOCA, the prevalence of endothelial dysfunction is somewhere between 45% and 75%.19,20

Although, to this point, no cut-off value has been universally accepted, it has been confirmed that moderate degrees of vasoconstriction (20% to 50%) with respect to the artery baseline diameter after the intracoronary infusion of acetylcholine have an important prognostic impact.18,21,22 Quantitative coronary angiography studies consider the variability of the technique when measuring changes in the mean luminal diameter of a segment with respect to the different doses of acetylcholine (usually the dose with the highest vasoconstriction with respect to the baseline one). Small imaging variations due to respiratory movements in every cine coronary arteriography, different limits of the study segment in the different measures taken, the analysis of diameters at different times of the cardiac cycle between the baseline image and maximum vasoconstriction, and the operator’s variability are the reasons why vasoconstriction can only be confirmed after variability is excluded from this measuring process. Several studies have established this variability (2 times the standard deviation of the percent difference) somewhere between 3% and 6%. Therfore, endothelial dysfunction is defined as a vasoconstrictor response that is greater than this variability.23,24

The pathophysiological factors of vasospastic angina, both in their macro and microvascular manifestations are less known and, also, probably multifactorial. Vasospastic angina has been associated with the presence of coronary plaques, vascular smooth muscle cell hyperreactivity, a high baseline vagal tone, hyperreactivity to sympathetic stimulation, and finally, to a significant degree of endothelial dysfunction.10 Vasospastic angina, both macro and microvascular, is more common among women.4 The traditional criteria to define vasospastic angina of macrovascular origin have been described by the Coronary Vasomotion Disorders International Study Group (COVADIS).5 In their document they describe the diagnostic criteria of this disease that go beyond the traditional definition of variant angina described by Prinzmetal et al.25. We should mention that, unlike the definition of endothelial function where baseline angiography is used as the reference, to define macrovascular spasm the COVADIS group recommends assessing the coronary spasp in the segment with the greatest constriction of all after the administration of acetylcholine and then compare it with the diameter of the same segment after the infusion of nitroglycerin.4 Also, this group recommends the use of drug provocation testing performed by intracoronary infusion of acetylcholine given its high sensitivity and specificity values (90% and 99%, respectively).26 Based on former studies and the traditional definition, the prevalence of epicardial coronary artery vasospasm, whether associated with microvascular spasm or not, occurs in 30% to 40% of the patients with INOCA.6,27

Fewer consensus documents have been published on the definition and diagnosis of microvascular spasm.28,29 Over the last few years, the appearance of thoracic pain and changes on the ECG suggestive of ischemia in response to acetylcholine and in the absence of macrovascular spasm have been accepted for the diagnosis of microvascular spasm (located in the arterioles). By this definition, 25% of the patients with INOCA meet the microvascular spasm criteria.27

TEST PERFORMED BY INTRACORONARY INFUSION OF ACETYLCHOLINE

Preparing the patient

The best way to prepare patients eligible for the coronary vasoreactivity test with acetylcholine is still under discussion. Historically, these procedures used to be performed in a dedicated procedure while avoiding and withdrawing all kinds of vasodilator drugs (like calcium channel blockers and nitrates) for, at least, 18 hours before the infusion of acetylcholine.27,30,31 However, after the publication of the randomized clinical trial CorMicA and the consensus document of the European Association of Percutaneous Coronary Interventions (EAPCI) on the study of patients with INOCA, conventional wisdom has changed.6,7 Currently, the use of intracoronary functional testing is recommended including the vasoreactivity test to acetylcholine within the same diagnostic procedure where the coronary angiography is performed.

This brings greater comfort to the patient, uses cath lab resources more efficiently, and alleviates the pressure of the hospital agenda. In any case, this procedure should be fully adapted to the needs and possibilities of every cath lab; in polymedicated patients with vasodilators or in inexperienced centers using this test the scheduled procedure should be used.

If radial access is used in patients eligible for a coronary vasoreactivity test the administration of calcium channel blockers to prevent radial spasm is ill-advised. In these cases, the administration of low doses of nitroglycerin through the introducer sheath (100 µg to 200 µg) can be considered. However, its effect will probably mostly be gone by the time acetylcholine is infused. Also, the coronary vasoreactivity test can be performed after studying microvascular function with a pressure guidewire (with the corresponding administration of intracoronary nitroglycerin before advancing the guidewire).6,7 In this case, a 2- to 3-min washout period should be observed before the infusion of acetylcholine.6,7

Finally, a specific informed consent should be obtained before running any vasoreactivity tests. Also, 12-lead ECG monitoring is required to assess the results. The use of radiotransparent wiring and electrodes is advised here to avoid interfering with the cine-fluoroscopy images obtained for each of the doses infused during coronary angiography. Figure 3 shows a schematic sample of how to prepare a patient before running a coronary vasoreactivity test with intracoronary acetylcholine.

Figure 3. Preparation of the patient before running any vasoreactivity tests. ACh, acetylcholine; Ca, calcium; Cine, cine coronary arteriography; IC, informed consent; NTG, nitroglycerin.

Regarding the use of beta-blockers, certain groups also recommend their cessation before running the test to avoid any possible vasoconstrictor effects. Until more scientific data become available, the opinion of this group is that beta-blockers do not affect the results of the test significantly and in no way give false negative results.

Preparing the acetylcholine

The acetylcholine available in Spain is a preparation for the intraocular injection of 20 mg of acetylcholine chloride (powder) for its dilution in a 2 mL vial of physiological saline solution. After the solution has been prepared, the drug is still unstable, which is why the best thing to do is to prepare it right before the test; if several consecutive tests are going to be performed, the same preparation can be used. Figure 4 summarizes the way to prepare the acetylcholine solutions suggested for the test. An important safety tip is to identify correctly every solution of acetylcholine we will be using; saline solution systems and color syringes for every dose can be useful.

Figure 4. Preparation of growing doses of acetylcholine. ACh, acetylcholine; DS, diameter stenosis; PSS, physiological saline solution.

Intracoronary infusion protocol

Over the last 30 years, different protocols on the administration and doses of intracoronary acetylcholine have been used. Table 2 shows the different protocols used in landmark studies.^{6,10,19,29,30,32-34} There are differences regarding the routes of administration (manual infusion through guide catheter or controlled selective infusion into an artery through an infusion pump and microcatheter), the number of doses infused (from 2 to 4), the amount of acetylcholine used (from 0.3 µg to 200 µg), and the infusion time (from 20 seconds to 3 minutes). Below we will be seeing the most widely accepted protocols based on the objective pursued (endothelial function assessment or vasospasm provocation) followed by a proposal according to the last consensus documents published to this date.

Table 2. Comparison of the different protocols of coronary vasoreactivity to acetylcholine

Group	Infusion method	Doses used	Infusion time per dose	Comments
Harvard Working Group30	Infusion through microcatheter and infusion pump	4 dilutions of 10–7, 10–6, 10–5, and 10–4 per liter (infusion at a rate of 0.8 mL/min) into the LCA	2 minutes	– Designed for endothelial function assessment – A final concentration of 10–9, 10–8, 10–7, and 10–6 is estimated (equivalent to a selective total dose per artery of 0.03 µg, 0.3 µg, 3 µg, and 30 µg) – It is performed on the LCA
Mayo Clinic32	Infusion through microcatheter and infusion pump	3 dilutions of 10–6, 10–5, and 10–4 per liter (infusion at a rate of 1 mL/min) followed by a bolus of 100 µg (through the same catheter)	3 minutes (final bolus for 20 to 30 seconds)	– Mixed protocol for endothelial function assessment (equivalent to a selective total dose per artery of 0.5 µg, 5 µg, and 50 µg) and vasospasm assessment with a bolus of 100 µg – It includes the functional assessment of microcirculation with Doppler guidewire during the infusion of acetylcholine – It is performed on the LCA
Korea Working Group33	Manual infusion through guide catheter	3 doses of 20 µg, 50 µg, and 100 µg into the LCA	1 minute	– It is performed on the LCA
Japanese Circulation Society10	Manual infusion through guide catheter	3 doses of 20 µg, 50 µg, and 100 µg into the LCA In the absence of vasospasm 2 doses of 20 µg and 50 µg into the RCA are advised	20 seconds	– Vasospasm provocation test on the LCA and RCA – The implantation of an electrode catheter to perform it is advised
Standford Working Group19	Manual infusion through guide catheter	4 doses of 20 µg, 50 µg, 100 µg, and 200 µg into the LCA	1 minute	– It is performed on the LCA
Stuttgard Working Group34	Manual infusion through guide catheter	4 doses of 2 µg, 20 µg, 100 µg, and 200 µg into the LCA In the absence of vasospasm into the LCA an 80 µg dose into the RCA is advised	20 seconds	– It studies both the LCA and the RCA
The CorMicA trial and the COVADIS Working Group6,29	Mixed pump and manual infusion	3 growing doses of 0.18 µg/mL, 1.82 µg/mL, and 18.2 µg/mL administered using an infusion pump through the guide catheter The procedure is completed with a manual bolus of 100 µg (50 µg into the RCA)	2 minutes for every growing dose, and 20 seconds for the final bolus	– It is performed on the LCA after microcirculation assessment with adenosine through a pressure guidewire – It assesses the endothelial function and the vasospasm provocation test in the same procedure
Protocol of the ACI-SEC (present document)	Manual infusion through guide catheter	3 doses of 2 µg, 20 µg, and 100 µg into the LCA In case of suspected vasospasm into the RCA the test should be started in this artery with doses of 2 µg, 20 µg, and 50 µg	20 seconds	– For endothelial function assessment purposes, the doses should be infused more slowly for 2 to 3 minutes – It is performed on the LCA
ACI-SEC, Interventional Cardiology Association of the Spanish Society of Cardiology; RCA, right coronary artery; LCA, left coronary artery.

Endothelial function assessment

Growing doses of acetylcholine are used for endothelial function assessment. If this procedure is performed by selective drug infusion into 1 of the main coronary vessels with a microcatheter (usually the left anterior descending coronary artery), the concentrations used are 10 moL/L to 6 moL/L, 10 moL/L to 5 moL/L, and 10 moL/L to 4 moL/L. Considering the left anterior descending coronary artery flow (some 80 mL/min), it is estimated that the drug reaches concentrations that are 100 lower in coronary microcirculation. Using the microcatheter these dilutions are injected the into the proximal left anterior descending coronary artery or into the artery to be interrogated at a rate of 1 mL/min for 3 minutes or 2 mL/min for 2 minutes through an infusion pump.24,35 Infusion starts with the least concentrated dilution and, if no complications or overt vasospasm are reported the next infusion should start 2 to 3 minutes later. In practice, this method injects 0.5 µg, 5 µg, and 50 µg of acetylcholine in each of the doses. As already mentioned, in the presence of a non-dysfunctional vascular endothelium, the physiological response is the vasodilation of major epicardial vessels.

The procedure described, although widely used in clinical trials, is somehow complicated and expensive, which is why easier and more practical alternatives have been developed for macrovascular endothelial function assessment. The most important one that has already become the standard may be the one used in the ENCORE trials (Evaluation of nifedipine and cerivastatin on recovery of coronary endothelial function)36,37 consisting of the infusion of growing doses of 2 µg, 20 µg, and 100 µg directly into the left main coronary artery for 3 minutes each followed by the performance of an angiography after every dose. Also, it consists of the assessment of the arterial diameter compared to the one measured on the baseline angiography. If macrovascular endothelial function needs to be assessed, the recommendation is to follow this infusion pattern. As we will be seeing, this protocol has already been widely adopted in recent publications and, with minor changes, has become the go-to protocol for the diagnosis of coronary vasospasm although with a faster infusion of the doses.

Microvascular endothelial function can also be assessed using dedicated guidewires for the simultaneous measurement of coronary flow. In general, this procedure is performed using a Doppler guidewire (Combowire, Philips, The Netherlands),9 although the assessment can also be performed through thermodilution with thermistor-based temperature measuring guidewires (Pressurewire, Abbott, United States).38,39 Figure 2 shows 2 examples of this procedure.

Coronary spasm provocation testing

Although there are different protocols on doses and infusion times, the protocol recommended here for vasospasm provocation has been widely accepted by the most experienced groups. In addition, there are data available on its safety profile in many patients and is the protocol backed by the EAPCI in its recent consensus document.7

Three doses of 2 µg, 20 µg, and 100 µg are used in the left coronary artery, and 3 doses of 2 µg, 20 µg, and 50 µg in the right coronary artery. If the test is negative or inconclusive and the previous doses are well-tolerated, a 200 µg or a 80 µg dose can be used in the left or right coronary artery, respectively, if suspicion runs high.

Regarding the infusion time, a slow 20 second-bolus can be administered, although this is based on clinical tolerability. The highest doses, especially in the right coronary artery, often require infusions at a slower rate to avoid sinus arrest-induced bradycardia or atrioventricular block. It is important to carefully and slowly wash the guide catheter with a saline solution to avoid the sudden injection of the remaining drug into the catheter by the time the cine-fluoroscopy imaging is acquired. After every dose both the symptoms and the repolarization and angiographic changes should be assessed while paying special attention to the appearance of epicardial spasms or significant reductions of coronary flow velocity. At the end of the test, intracoronary nitroglycerin is infused (200 µg to 300 µg) and spasm is solved within a few seconds.

Safety and complications

Before indicating the test, the presence of factors that may be correlated with a risk of complications associated with the intracoronary infusion of acetylcholine should be discarded. The test should be carefully performed in patients with a past medical history of asthma or bronchospasm and serious disorders of automaticity and cardiac conduction.

Although safe in experienced hands, coronary vasoreactivity tests to acetylcholine are not stranger to potentially serious complications. These tests should always be performed paying extra care by trained personnel and ready to face the possible complications that may arise. In a metanalysis of different studies with over 6000 procedures, the rates of major (eg, ventricular arrhythmias, need for cardiopulmonary resuscitation or infarction), and minor complications (symptomatic bradycardia, transient atrioventricular block, appearance of ventricular arrhythmias or air embolism) were 1% and 6%, respectively.40 We should mention that no death was reported in this metanalysis.40 Table 3 shows the most common complications and their corresponding treatments.

Table 3. Complications associated with the intracoronary infusion of acetylcholine

Complication	Percentage	Comment	Treatment
Bradycardia and/or transient atrioventricular block	3.23%	More common in high doses and when infused fast, especially into the RCA	Stop the infusion for a few seconds until going back to rhythm. Study the possibility of going on with the test at a slower infusion rate
Appearance of atrial fibrillation	2.38%*	It is often self-limiting, but also fast, and its clinical tolerance is poor. It is a reason to stop the test whose outcome will be undetermined	If hemodynamic tolerance is good, use antiarrhythmic drugs; if poor, study the possibility of electrical cardioversion
Ventricular fibrillation, ventricular tachycardia or need for resuscitation	1.00%	Due to acute ischemia following flow-limiting vasospasm	Nitroglycerin and defibrillation
Shock and/or myocardial infarction	0.07%	Due to flow-limiting spasm at multivessel or left main coronary artery level	Nitroglycerin plus inotropic support +/– ventricular support
Transient hypotension	0.05%	It is often unsignificant	Stop the infusion for a few seconds until going back to rhythm. Study the possibility of going on with the test at a slower infusion rate
Coronary artery dissection	0.02%	Catheter-induced coronary artery dissection	Stenting
Air embolism	0.02%	Operator-dependent complication; it is more common when infusion is performed through a microcatheter. It can be serious if not treated fast	Administer oxygen at 100% and wash the artery with saline serum multiple times (after making sure there is no more air). Inotropic and/or ventricular support (or both) may be needed
Catheter-induced spasm	0.02%	More common in the RCA	Try to avoid nitroglycerin in the absence of flow lost. It is often a transient phenomenon
The percentages disclosed were estimated based on 6183 procedures reported in 9 different studies. * According to the CorMicA trial, the rate of atrial fibrillation with the fastest doses infused was 6%.6 RCA, right coronary artery. Adapted with permission from Ciliberti et al.40

During the infusion of acetylcholine, sinus bradycardia, sinus arrests or episodes of atrioventricular block are common. This is often associated with too fast infusions, especially in the right coronary artery. If these complications occur, infusion should stop for a few seconds and restarted at a slower velocity. Atrial fibrillation can sometimes occur, but it often solves spontaneously; the most persistent cases often solve after the administration of amiodarone or other antiarrhythmic drugs. If bradyarrhythmias make a comeback, the test should stop immediately or be performed with a transient pacemaker in very selected cases where the test is considered indispensable.

An unwanted effect of the test is flow-limiting vasospasm that is not well-tolerated. In general, the consequences depend on the time elapsed between the occurrence of the vasospasm and the infusion of intracoronary nitrates to reverse it. The ischemia originated can cause hypotension and ventricular fibrillation that should be treated with nitroglycerin and immediate defibrillation. To stop this from going unnoticed, the patient’s blood pressure should be checked halfway into the infusion of acetylcholine, especially after the highest doses have been infused and when injected into a dominant left coronary branch. Under no circumstance a growing dose of acetylcholine should be infused if a significant or flow-limiting spasm or any other important complication have been spotted after the infusion of lower doses. Also, we should remember that, at the end of the infusion, the guide catheter still contains 2 mL of acetylcholine dilution that should be slowly pushed with a saline solution to stop it from entering the bolus with the injection of contrast. Same as it happens with any other invasive coronary procedures, and especially in this test, preloaded nitroglycerin should be available and ready to be infused. In most of the cases its infusion causes vasodilation, and fast flow recovery without needing further doses. On the other hand, atropine is a cholinergic receptor antagonist that can be used as an antidote when necessary.

Some operators perform the vasoreactivity test using the pressure guidewire inside the coronary artery as a safety measure. This brings more stability to the catheter, provides better selective infusion of dilutions, and allows us to monitor distal pressure (that can decrease in the case of flow-limiting spasm). Also, it controls the velocity of manual infusion in case of a long infusion without a pump (temperature or velocity changes are indicative that infusion is happening too fast). However, we should remember that the passage of the guidewire itself can cause vasospasm. Actually, it can simulate pseudo-spasms in tortuous arteries due to curve rectification.

INTERPRETING THE CORONARY VASOSPASM PROVOCATION TESTING

General concepts

Interpreting this test rests on 3 basic pillars:

 

 

DS = 100 – [(MLD_Ach / RVD_NTG) × 100]

In practice, it is better to use the quantitative coronary angiography on the proximal segments of major arteries than in more distal segments where the reference diameter is often small and, according to the formula described above, could underestimate the DS.

Possible test results

Figure 1 shows the 4 results that can be obtained from a vasospasm provocation test performed by the infusion of intracoronary acetylcholine:

 

LEGAL ASPECTS PERTAINING TO THE USE OF INTRACORONARY ACETYLCHOLINE

The use of drugs in off-label indications different from those approved in their instructions for use and outside the clinical trial setting like intracoronary acetylcholine for diagnostic purposes requires the approval of local pharmaceutical committees. Because the Spanish Agency of Medicines and Medical Devices accepts the use of these drugs under very particular circumstances no general consensus has been achieved and local approvals are still required.

Also, in observance of Royal Decree 1015/2009 of 19 June,41 the use of a drug through a route of administration different from the one described in the drug labeling requires the provision of information as well as the patient’s written informed consent prior to its administration. For that reason, some centers also require the signing of a specific informed consent to be able to use intracoronary acetylcholine. These documents are available on the center intranet or the hospital pharmacy.

CONCLUSIONS

Figure 5 summarizes the key takeaways of this document. In conclusion, vasoreactivity testing with acetylcholine is an essential part of the assessment of patients with non-obstructive coronary artery disease and symptoms or ischemia. The result of this assessment allows us to target specific therapies and has proven effective in the routine clinical practice. Cath labs should be prepared to perform this kind of tests, and computers should be ready to use and interpret them.

Figure 5. Key takeaways of this document. ECG, electrocardiogram; INOCA, ischemia with non-obstructive coronary arteries; MINOCA, myocardial infarction with non-obstructive coronary arteries.

FUNDING

This document had no funding whatsoever.

AUTHORS’ CONTRIBUTIONS

E. Gutiérrez and J. Gómez-Lara equally contributed to the manuscript first draft, and to the figures, and tables. The remaining authors performed a thorough revision of the paper and made comments and changes to its content and form.

CONFLICTS OF INTEREST

None reported.

REFERENCES

INTRODUCTION

Over the last 2 decades, interventional cardiology has been one of the fastest growing medical specialties. The invasive management of acute coronary syndrome, the optimization of short and long-term results of percutaneous coronary intervention (PCI) techniques, and the development of percutaneous techniques to treat a large number of structural heart disease cases have become very popular. This has facilitated the management of patients with cardiovascular diseases who require diagnostic or therapeutic invasive techniques at the unit of interventional cardiology (UIC) at one time or another.

Parallel to this increasing healthcare demand, we have seen another very significant increase in the number of UIC-capable centers, the need for material and human resources, and development of the technology used. Some rules and regulations have changed over the last few years. The latest clinical practice guidelines were published by the Spanish Society of Cardiology (SEC) 20 years ago,1 and the very latest recommendations from the Spanish Ministry of Health were established almost 10 years ago.2 That is why it seems necessary to update these recommendations, in our field, on the hemodynamic and interventional cardiology requirements and adapt them to the current situation where most UICs already have continuous infarction care plans and structural heart programs implemented. For this reason, the Interventional Cardiology Association of the Spanish Society of Cardiology (ACI-SEC), the Spanish Society of Cardiology Working Group on Ischemic Heart Disease and Acute Cardiovascular Care, and the Spanish Association of Nursing in Cardiology (AEEC) have published this document.

HOSPITAL REQUIREMENTS

This document divides cath labs into autonomous cath labs (run with medical personnel from the center) and satellite or supervised cath labs (run with personnel from other centers to secure the provision of healthcare).

These are the requirements for hospitals to qualify as PCI-capable centers (figure 1):

 

 

Figure 1. Summary of hospital requirements regarding human and material resources that should become available at the interventional cardiology unit. PCI, percutaneous coronary intervention.

These requirements are applicable both to autonomous and satellite units. Regarding cardiac surgery, its existence in situ should not be considered a requirement per se for the center to qualify as a PCI-capable UIC.3 Also, a protocol needs to be agreed upon with a cardiac surgery unit to facilitate the transfer of patients for emergency surgeries in less than 60 min. Traditionally, structural heart procedures have not been deemed necessary to perform procedures such as valvuloplasties or percutaneous closures of interatrial defects. However, with the rise of structural heart procedures of higher risk and complexity like transcatheter aortic valve implantation (TAVI) or the management of mitral regurgitation using the MitraClip system, this question has gained popularity and the current clinical practice guidelines consider it necessary.

HUMAN RESOURCES

Chief, Director or Head of the UIC

The chief of the UIC should be a cardiologist accredited in the practice of interventional cardiology by the ACI-SEC. Although back in 2011, the Spanish Ministry of Health recommended, at least, more than 5 years of professional practice and over 500 procedures performed,2 we believe the time has come to update these numbers. Therefore, we recommend over 1000 diagnostic procedures and over 500 therapeutic procedures performed.

The basic functions and responsibilities of the head of the UIC are:

 

 

Medical staff

As explained in the “Training and competences” section below, the UIC medical personnel should hold a valid degree as cardiology specialists issued in Spain, follow the recommendations established by the ACI-SEC regarding specific training in interventional cardiology,4 and be in possession of the radiation protection course level 2.5

The functions and responsibilities of the interventional cardiologists who work at the UIC are:

 

 

The recommended number of cardiologists with full dedication to interventional cardiology to provide scheduled care at an UIC with just 1 cath lab and be able to cover vacations is 3. At UICs with 2 cath labs the recommended number of cardiologists with full dedication to interventional cardiology is 5. For every additional cath lab over 2, 1 interventional cardiologist should be added. This is applicable to supervised cath labs too in such a way that in those centers where the UIC acts as the reference to 1 or more supervised cath labs, the number of interventional cardiologists needed should increase by a factor of 1 for every supervised cath lab available. In any case, if the UIC has continuous infarction care plans implemented (on a 24 hour/day basis 365 days/year), the minimum number of interventional cardiologists required for its correct functioning is 4.6 In order to guarantee the availability of continuous infarction care plans, in some centers (especially those with just 1 cath lab) it may be necessary to hire part-time interventional cardiologists who also work in other areas of cardiology.

The UIC accredited health professionals will facilitate and engage themselves in the development of training programs for both internal medicine residents (IMR) and internship recipients as long as the UIC is accredited to that effect. On the other hand, to perform special procedures, other health professionals who may not be part of the UIC such as cardiology specialists (echocardiography specialists or acute coronary care unit cardiologists) and anesthesiologists may be requested.

Nurse supervision

Nurse supervisors should have an adequate level of experience and training in interventional cardiology, as well as other specific functions and responsibilities. It is advisable that they should be accredited as experts in interventional cardiology by the AEEC.7 These are their responsibilities:

 

 

Nursing staff

The minimum requirements for the nursing staff who work at the UIC are:

 

 

Also, the UIC nursing team needs to be competent in cardiovascular care in general and in the early management of patients, their mental preparedness, and be able to handle postprocedural monitorization. Also, they need to be experienced in the management of cardiovascular disease, critical coronary care unit, management of cardiovascular drugs, be skilled starting IVs, experienced using cardiovascular tools, competent in the use of interventional cardiology tools and skilled using them.2,8

Regarding their competences at the UIC, the nursing team can be divided into: instrument nurses, circulating nurses, and polygraph nurse specialists; still, the entire nursing team needs to be competent in the 3 areas described above. The team should also be skilled in preparing the patients before the procedure and immediate monitorization are tasks that should be performed by expert UIC nurses.

The number of nurses required for the proper functioning of the UIC depends on the type of procedure performed. In order to perform diagnostic studies and PCIs, the minimum number of nurses is 2 (in this case, the same nurse does both the circulating and polygraph monitoring tasks) being 3 the ideal number. At least 3 nurses are required to perform structural heart procedures. The AEEC estimates that for quality care purposes, the proper number of nurses at a cath lab should be 3 in order to cover the aforementioned instrument, circulating, and polygraph monitoring tasks.8 In any case, at least 2 of these 3 nurses need to be experts in order to provide safe and quality care for the patients during and after cardiac catheterization.

Radiology technicians

Since radiation protection training is mandatory for both the UIC medical staff and the nursing team, radiology technicians are not considered essential workers at the UIC. Actually, most UICs simply don’t have them among their staff. However, if they are among the UIC staff, they need to take regular care and maintenance of the radiology equipment and know the different software applications and quantitative coronary angiography systems. Also, they need to understand how non-angiographic imaging modalities (intracoronary ultrasound and optical coherence tomography) and physiological systems (intracardiac pressures and intracoronary pressure guidewires) work. Also, they need to make sure that radiation emissions are safe both for the patients and the healthcare personnel.

Patient care technicians and non-professional healthcare workers

Patient care technicians (PCT) play an important role preparing the patients and helping the nursing team. At least 1 PCT needs to be present in UICs with 1 or 2 cath labs, and 2 PCTs in UICs with more than 2 cath labs.

The administrative personnel and auxiliary health workers are essential employees at the UIC. Administrative personnel handle medical appointments and all sorts of healthcare related documents. Auxiliary health workers are in charge of swiftly escorting the patients in and out of the hospital. At least 1 administrative clerk with full dedication to the UIC should be present in large volume centers with more than 1 cath lab. The cleaning personnel prepare the cath lab between cases while maintaining the proper hygienic conditions.

TRAINING AND COMPETENCES

The SEC, through the ACI-SEC, has been implementing an internal accreditation system for healthcare professionals and training centers since 1998.4 The requirements to access this accreditation system and the core curriculum update in interventional cardiology proposed by the European Association of Percutaneous Cardiovascular Interventions (EAPCI)9 are the basis of the recommendations described below.

Interventional cardiology training

Training in interventional cardiology should guarantee an absolute knowledge of all diagnostic and therapeutic invasive techniques available. Over the last few decades, Spanish cardiologists have been treating not only coronary artery disease but also non-valvular10 and valvular11,12 structural heart diseases percutaneously. It is important to stress that interventional cardiologists are also involved in the comprehensive cardiac management of the patients including the indication for the procedure, evaluations using imaging modalities, the management of all possible complications, and clinical follow-up.

The prerequisites to obtain the professional accreditation in interventional cardiology are:

 

 

Training centers

In order to guarantee proper training in interventional cardiology, the clinical practice guidelines on the management of myocardial revascularization recommend13 that training should be carried out in large volume centers with an independent UIC and a structured acute coronary syndrome care program on a 24/7 basis.

In Spain, the ACI-SEC has an accreditation program with training centers adapted to the reality of our context that establishes the following minimum requirements4:

 

 

Keeping the accreditation

There is a direct correlation between results and the volume of PCIs performed per center and operator, both regarding PCIs in general and14 in PCIs to treat infarctions.15 In order to remain competent in performing PCIs to treat acute coronary syndrome, interventional cardiologists need to perform at least 75 PCIs every year. This represents a total of 400 PCIs performed each year by PCI-capable centers on a 24/7 basis). They also need to perform at least 75 PCIs each year to treat acute coronary syndromes (a total of at least 200 annual PCIs per center). Ideally, centers and operators with fewer PCIs performed should partner with larger volume centers.13

Under the current accreditation system, at the time this manuscript was being written, in order to maintain competency the ACI-SEC required that every 5 years, all accredited professionals will be compelled to justify the activity developed during this time. The applicants will need to prove that they performed at least a total of 75 annual PCIs documented and certified by the head of the UIC.4

MATERIAL RESOURCES

Physical space

The ideal location of the UIC is a place close or with easy access to the emergency unit and the cardiology unit hospitalization areas. The UIC should be built with the following physical spaces in mind:

 

 

Conditions of sterility and air quality

UNE regulation 100713 dated September 2005 classified all UICs as high-risk areas16, class I, and categorized them traditionally as operating rooms type B (ISO class 7),17 indicative that the air diffusion system recommended is turbulent flow.

According to UNE regulation 17134018 which classifies hospital aeras based on risk and type of ventilation/filtration used, cath labs are ranked as high-risk areas. The UICs built from 2012 onwards need to meet the aforementioned regulation to guarantee a sterile environment to be able to perform all kinds of minimally invasive procedures like TAVI, left atrial appendage closures, and use of the MitraClip system. Also, the conditions of sterility and asepsis allow us to use these UICs as conventional operating rooms too (for example, for the management of vascular complications). However, UICs built before this regulation became effective are not bound to it unless remodeled (table 1).

Table 1. Conditions of sterility and quality of air that all current cath labs should meet

• • • •

− Minimum advisable flow recirculation with 25 movements/hour of which ≥ 1200 m3/h should be with fresh air from outside

− Single air-handling unit

− Recirculated air should be treated exactly the same as the outside air by the same air-conditioner

− Periodic microbiological tests

− Air velocity at the room occupancy area between 0.2 m/s and 0.3 m/s

− Have, at least, 3 levels of filtration including these types of filters: Pre-filter EU4 Air-conditioning EU9 air filter Final H13 filter in the surgical area

UICs should provide enough surgical coverage to perform procedures under conditions of sterility. The use of disposable material is also advised.19 Under conditions of special risk of infection for healthcare personnel, personal protection equipment is advised.20 In any case, all measures related to sterility at the cath lab and infection avoidance for the healthcare personnel should be discussed with both the preventive medicine and risk management units.

Radiology equipment and clinical support systems

In general, the UIC radiological and additional equipment should include (figure 2):

Figure 2. Equipment present at the cath lab. 1: patient table. 2: x-ray tube. 3: radiation shielding lead glass with upper leaded glass section and articulated adjustable arm mounted on the ceiling. 4: leaded skirt mounted on the table. 5: automated contrast media injector. 6: on/off ceiling light with adjustable articulated arm. 7: monitors. 8: infusion pumps. 9: anesthetic and respiratory equipment. 10: crash cart or code cart with defibrillator. 11: smart cabinet for material storage with automatic replacement. 12: table with the equipment needed to perform the procedure. 13: console of the pressure wire.

 

 

Image acquisition systems and storage

The image acquisition system should be digital with a proper dynamic range for routine clinical applications. It should cover the low doses of the different imaging modalities of x-rays and the higher doses of digital acquisition including the most demanding ones of the digital subtraction angiography. The frequency range in pulsed fluoroscopy or graphic representation should be of 30 or more images per second. It should allow processing, visualization, and digital storage.

This equipment needs to include coronary and ventricular quantification applications. Currently, there are applications available for quantitative computed tomography assessment to plan procedures, and fusion systems of transesophageal echocardiography plus digital angiography that can be useful when performing interventional procedures to treat structural heart diseases.

The images of every patient will be saved and stored permanently in a filing system compatible with multiple DICOM modality worklist services (digital imaging and communication on medicine) of cardiac images with integrated DICOM-3 services. These images need to be stored in the corresponding hospital or health service PACS (picture archiving and communication system) so that all studies can be seen and analyzed from the different working stations connected to this server. For that purpose, TCP/IP communications protocols (transmission control protocol/ internet protocol) are required. These protocols should be used in full compliance with data protection legislation. The capabilities of compact disc and digital versatile disc recording and reading are advisable in compliance with the DICOM standard anticipating the possibility of exporting images and angiographic series to other imaging formats.

For real-time image processing and simultaneous image acquisition purposes, a working station will be required for case review and analysis that will join the working station of the image acquisition system. It should be located in the same control zone as the x-ray and polygraph equipment.

Resuscitation and life support systems

UICs should have specific resuscitation and life support systems:

 

 

Specific material to perform coronary interventions

Added to the conventional material used to achieve diagnosis and perform coronary interventions (diagnostic catheters, guide catheters, angioplasty guidewires, angioplasty balloons, and coronary stents), it is advisable to have specific coronary stents available to treat coronary perforations, and plaque modification devices to treat nondilatable coronary lesions with conventional balloon or heavily calcified coronary lesions.21

Intracoronary diagnostic tools

In a large number of patients, the use of pressure guidewires or intracoronary imaging modalities will be required as established by the latest clinical practice guidelines on the management of myocardial revascularization.13

Clinical practice guidelines consider pressure guidewires as the proper tool to identify hemodynamically relevant coronary lesions in stable patients (indication class I, level of evidence A) and guide revascularization in patients with multivessel disease (indication class IIa, level of evidence B).13

Also, clinical practice guidelines indicate the use of intracoronary imaging modalities (both intracoronary ultrasound and optical coherence tomography) to study the mechanisms of stent failure and for implant optimization purposes in selected patients (indication class IIa, level of evidence B). Also, intracoronary ultrasound is considered the imaging modality of choice to study the severity of left main coronary artery lesions and for result optimization purposes (indication class IIa, level of evidence B)13.

Therefore, we believe it is necessary for UICs to have functional assessment methods available (eg, pressure guidewires) and intracoronary imaging modalities as well.

Circulatory support systems

Circulatory support systems are required at the UIC to approach complex angioplasties in high-risk patients and for the management of hemodynamically unstable patients or cardiogenic shock. Actually, this is very important in centers with continuous infarction care programs running, especially large volume centers and satellite cath labs without surgical coverage in situ. These systems can be:

 

 

SPECIFIC CONSIDERATIONS

Supervised cath labs

Over the last decade, the model of satellite or supervised cath labs in large volume center units has been widely implemented. The reason for this is to bring coronary intervention techniques to a larger number of centers so patients can have access to these services without detriment to the advantages that experienced tertiary levels bring. The characteristics of a satellite or supervised cath lab are:

 

 

A written agreement will need to be signed between the management of both centers for the provision of these services including a budget with all the expenses derived from buying the material required. These centers can be included in healthcare networks.

According to the legislation that regulates the planning and arrangement of the healthcare services provided by each Spanish autonomous community, satellite cath labs can have extraordinary continuous activity programs available on a 24/7 basis 365 days/year to provide urgent care especially within the framework of institutional infarction code programs. The implementation of these programs will be the sole responsibility of the reference UIC.

Structural heart procedures or urgent procedures will not be performed in the supervised cath lab. but in the reference center. However, very complex coronary procedures or interventions requiring special devices in clinically stable patients are ill-advised and they should be performed at the reference center.

Optimization of the infarction care program (primary angioplasty program)

The requirements and needs of infarction care networks have already been described in detail.6 In summary, hospitals with primary angioplasty programs require:

 

 

Structural heart intervention programs

The specific recommendations to perform structural heart procedures are:

 

 

Latest programs: cardiac arrest code and management of acute pulmonary embolism

Over the last few years, the management of cardiac arrest and acute pulmonary embolism has improved significantly. Actually, interventional cardiology has progressively gained interest in these conditions.

Regarding cardiac arrest, performing emergency coronary angiographies to treat acute coronary syndrome can bring clinical benefits. Our recommendation is that patients with out-of-hospital cardiac arrests should be transferred to specific centers. Actually, this kind of care for this type of patient has become a customary practice for some hospitals and is now called “cardiac arrest code”. Requirements for these centers are:

 

 

Maastricht types III and IV controlled asystole organ donation programs are not required but highly recommended.

Regarding acute pulmonary embolism, more and more UICs have included the management of this condition in their repertoire using embolectomy catheters in hemodynamically compromised patients contraindicated for thrombolysis.

Based on experience and efficiency, both the cardiac arrest code and the management of pulmonary embolism should be handled by personnel from the continuous infarction care program-according to the internal reality of every hospital and the healthcare regulations of the department of health of the Spanish autonomous community concerned.

CONCLUSION

Over the last few years, the wide invasive management of acute coronary syndrome, development of acute myocardial infarction care networks, creation of supervised cath labs, the arrival and development of new diagnostic and therapeutic coronary techniques and coronary interventions for the management of structural heart disease, as well as legislation changes have changed the equipment, and human resources associated with UICs. This document comes as a response to the need for adapting the current situation to the recommendations in our context regarding requirements in hemodynamics and interventional cardiology. In the future, the recommendations published in this document will need to be updated based on the future steps interventional cardiology may take.

FUNDING

No funding.

CONFLICTS OF INTEREST

The authors declared no conflicts of interest regarding this manuscript. R. Moreno is associate editor of REC: Interventional Cardiology; the editorial protocol of the journal was observed to guarantee an impartial manuscript handling.

REFERENCES

INTRODUCTION

Ischemic heart disease is the leading cause of death in Mexico. Consequently, the number of patients with acute coronary syndrome (ACS) or stable chronic coronary syndrome who will require medical services is not expected to go down during the pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The ongoing need to manage this disease during the COVID-19 pandemic compels us to recognise the exceptional situation and to search for an adequate response.

Several places across the world have suspended the management of ischemic patients or decided to use less invasive—also less effective—treatments. The idea behind this is to reduce the risk of contagion for patients, relatives, and healthcare workers. However, this decision has created huge controversy in the medical establishment: is it safe? Is it ethical? Is the safety of the medical team more important than the patients’ health? For how long should this measure be effective?

The Mexican Interventional Cardiology Society (SOCIME) backed by the Mexican Society of Cardiology (SMC), the National Association of Cardiologists of Mexico (ANCAM), and the National Association of Cardiologists at the Service of State Workers (ANCISSSTE) have published this document to guide the medical personnel in the decision-making process during the current COVID-19 pandemic.

PATIENT CLASSIFICATION

Healthcare workers looking after patients with ischemic heart disease should classify them into 2 groups based on the information available during the healthcare process: 1) patients with suspected SARS-CoV-2 infection or patients with symptoms of concurrent myocardial ischemia or other heart-related complications; 2) other patients, without a diagnosis or suspicion of SARS-CoV-2 infection, who require medical attention due to symptoms of myocardial ischemia. The reason for making this subdivision is to minimise the contagion of other patients, relatives, medical and hospital personnel by avoiding contact between uninfected patients and patients with SARS-CoV-2. Before being transferred to the cath lab all patients will be actively screened for the presence of fever, cough, and respiratory distress. The patients’ temperature and arterial oxygen saturation will need to be checked as well.

STABLE CHRONIC CORONARY SYNDROMES

There is general consensus that invasive procedures—whether percutaneous or surgical—should be differentiated in patients with stable chronic coronary syndrome during the current health emergery.1^,2 The undersigned working group that participated in the writing of this document agrees on the adoption of this measure. However, it also admits that the number of patients who will not receive proper care will end up accumulating and a proportion of these patients will turn into new cases of acute ischemia. In conclusion, patients with stable chronic coronary syndrome during the current pandemic should receive optimal therapy and be warned of the importance of seeking urgent medical attention in the presence of symptoms of ischemic instability.

ACUTE CORONARY SYNDROMES

In the current context of the COVID-19 pandemic, there is no unanimous agreement to define the optimal treatment strategy for patients with ACS. We will be reviewing the information available accumulated over a very short period of time on the different treatment proposals reported followed by the position and recommendations from this group.

Classification

ACSs can be divided into: a) ST-segment elevation ACS including ST-segment elevation myocardial infarction (STEMI) and b) non-ST-segment elevation ACS including non-ST-segment elevation myocardial infarction (NSTEMI) and unstable angina.

Diagnosis

Two recommendations should be followed to minimize the risk of contagion. The first one should be social distancing and limited contact with patients during the physical examination or while performing the transthoracic echocardiogram to obtain the maximum amount of information while minimizing physical contact with the patient; the second recommendation is the use of coronary computed tomography angiography as a fast non-invasive imaging modality to confirm or discard the presence of coronary heart disease as the cause for the symptoms when appropriate.3 The main elements for diagnosis are:

 

 

Management of STEMI

Primary percutaneous coronary intervention (pPCI) is the treatment of choice for coronary reperfusion. Fibrinolysis is spared for cases where percutaneous coronary intervention (PCI) is not available or when the patient transfer to a PCI capable hospital involves significant time delays.4 The COVID-19 pandemic has produced different points of view for the management of patients with STEMI; these different positions are indicative of the particular situations that medical societies are facing to design their recommendations.

Fibrinolysis as the strategy of choice

A report and the position adopted by opinion leaders recommend the use of fibrinolysis as the first reperfusion strategy in both uninfected patients and patients with suspicion or diagnosis of COVID-19. The PCI would be spared for cases of failed fibrinolysis and only if benefits exceed the possible risks.5 They recommend that patients with serious pneumonia due to SARS-CoV-2, unstable vital signs, and concurrent STEMI should receive support medical treatment only—no fibrinolysis or pPCI—until they have recovered from pneumonia. These recommendations are highly restrictive, do not anticipate the pPCI option and limit the possibility of bailout PCIs in selected cases.5

pPCI as the strategy of choice

Several medical societies are keeping to their usual recommendations during the current pandemic. Patients with STEMI (with or without suspicion of infection, with or without COVID-19) inescapably need medical attention and should receive pPCI as the reperfusion therapy, especially those with persistent angina or hemodynamic compromise; they also keep the bailout PCI option alive. They accept that fibrinolysis can be an alternative in patients with pneumonia due to SARS-CoV-2 who develop STEMI but remain stable.1^,2^,6 The Spanish Society of Cardiology (SEC) ranks pPCI as the preferred reperfusion strategy in most patients with severe pneumonia and difficulties moving or being transferred.7 At the present time, Spain is one of the countries with the highest contagion and mortality rates and its healthcare system has collapsed due to the excessive volume of patients with COVID-19; in the middle of this health crisis, consensus still favors the reperfusion of STEMI through pPCI.

Management of non-ST-segment elevation ACS

In general, the specific risk of complications of patients with NSTEMI or unstable angina should be identified to decide the best time to perform cardiac catheterization. Regardless of their risk, it is essential to know the patients’ coronary anatomy and based on the findings assess the revascularization method.8 As with STEMI, this routine common practice has changed during the current pandemic and several of the position papers on the management of ST-segment elevation ACS have been replicated.

Medical therapy as the strategy of choice

The general recommendation is to know the state of contagion before referring patients to the cath lab Patients without a diagnosis or suspicion of infection need to be tested to confirm or discard the presence of SARS-CoV-2. It is suggested that patients with suspicion of COVID-19 who have not been tested yet and those who have already tested positive should receive medical therapy. The interventional procedure should be deferred until they have recovered or the risk of contagion has gone down.7 It is recommended that patients without suspicion of infection or without COVID-19 (common patients) undergo PCI only if they are high-risk patients or remain unstable during the course of conservative treatment. Urgent PCIs will be spared only for patients with hemodynamic compromise or malignant arrhythmias regardless of their state of infection.6^,7

PCI as the strategy of choice

Here the usual recommendations still stands, which is why high-and-intermediate risk patients should undergo PCI, regardless of their state of contagion.8 In low-risk patients with COVID-19 or with severe pneumonia and who remain unstable it is advised to consider medical therapy and defer the procedure. Early PCIs facilitate early hospital discharges. In patients with multivessel disease the PCI should be favored over coronary revascularization surgery. Patients admitted to hospitals without cath lab capabilities should not be transferred. In these cases, conservative treatment is advised followed by early hospital discharges.1^,2

CONSENSUS ELEMENTS

The following variables were taken into consideration while the recommendations of this consensus document were being designed:

 

 

RECOMMENDATIONS

The objective of this document is to guide the decision-making process on the coronary revascularization of patients with ACS during the health emergency declared due to the current SARS-CoV-2 pandemic. Considering the elements described above and anticipating an epidemiological model similar to the one seen in countries like ours, we recommend making slight modifications to the management of patients with ACS while continuing to use the pharmacoinvasive reperfusion strategy prevalent in Mexico.

STEMI

Cardiovascular risk

We recommend that pharmacoinvasive strategy should start by identifying patients with higher risk of complications. The presence of 1 or more of the following characteristics is indicative of high risk:

– Age > 75 years.

– Cardiogenic shock (whether associated or not to mechanical complications).

– Refractory angina.

– Ventricular tachyarrhythmias.

– Bradyarrhythmia requiring temporary pacemaker implantation.

– Electrocardiographic pattern of diffuse ischemia.

pPCI

We recommend public and private hospitals with cath lab capabilities and, in particular, tertiary care or reference centers to keep offering pPCI over fibrinolysis. This is completely justified by its higher rate of success, lower risk of complications, and shorter hospital stays (hospital discharges within 36 h - 48 h). The fibrinolysis proposal as the primary reperfusion method even in hospitals with cath lab is questionable.

Fibrinolysis

We still recommend its indication as the reperfusion method in non-PCI capable centers. Unlike conventional pharmacoinvasive strategy, the transfer of stable patients with successful fibrinolysis for early elective cardiac catheterization is ill-advised; these patients should be followed and monitored later in time. Only patients with failed fibrinolysis should be transferred and only in the presence of hemodynamic or electric instability. In patients with severe pneumonia due to COVID-19 it is a valid option even for PCI-capable centers in the presence of high and growing volumes of suspicious or confirmed cases. Also, in the absence of high-risk markers, especially in patients admitted within the first 3 hours after symptom onset and without contraindications for fibrinolysis.

Periodic adjustment of reperfusion method

We recommend that in cities, regions, and hospitals with large volumes of patients with COVID-19 or suspected cases, whether critical, growing or rapidly spiking, the hospital management should decide on the most adequate reperfusion method with the heart team and the resources available. The primary reperfusion strategy should adjust periodically based on the temporal and geographic pattern of the infection.

The algorithm shown on figure 1 for the management of patients with STEMI during the current COVID-19 pandemic recommends pPCI as the method of choice for coronary reperfusion. The reperfusion strategy should change as the pandemic evolves with the necessary, periodic adjustments based on the modification criteria already described.

Figure 1. Therapeutic algorithm for the management of patients with STEMI during the current SARS-CoV-2 pandemic. The arrow thickness is indicative of the preferred therapy. +, present; ±, present or absent; bPCI: bailout percutaneous coronary intervention; CCTA, coronary computed tomography angiography; FL, fibrinolysis; MVD, multivessel coronary artery disease; pPCI, primary percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction.

NSTEACS

Regardless of the presence of SARS-CoV-2, low-risk patients who respond to medical therapy can be discharged from the hospital to be studied later in time if the risk of contagion is lower or if they have recovered from COVID-19. If the patient’s coronary anatomy needs to be documented prior to hospital discharge, an option here is to perform a coronary computed tomography angiography and, based on the findings, plan the PCI or discharge the patient. Moderate-or-high risk patients (according to the criteria described above) and those who become unstable during the course of conservative treatment should be transferred to the cath lab regardless of their state of contagion.

Most concepts described for the management of STEMI are valid in these patients. PCI-capable public and private hospitals with experienced personnel and the necessary resources should keep the PCI option open in light of its high rate of success and short hospital stays. In patients with significant multivessel disease the hospital stay should be short and PCI revascularizations should be prioritized over coronary revascularization surgeries.

In the algorithm shown on figure 2 for the management of patients with NSTEACS during the current COVID-19 pandemic the use of PCI is recommended in high-risk patients. However, the reperfusion strategy should be dynamic as the pandemic evolves with periodic adjustments based on the modification criteria already described.

Figure 2. Algorithm for the management of patients with NSTEACS during the current SARS-CoV-2 pandemic. The arrow thickness is indicative of the preferred therapy. +, present; ±, present or absent; CCTA, coronary computed tomography angiography; MT, medical therapy; MVD, multivessel coronary artery disease; NSTEACS, non-ST-segment elevation acute coronary syndrome; PCI, percutaneous coronary intervention; Tx, treatment.

Cardiovascular complications in patients with COVID-19

Patients with COVID-19 can have clinical signs of myocardial damage and secondary complications. Myocardial damage with elevated high-sensitivity cardiac troponin levels (7.2%), cardiogenic shock (8.7%), and arrhythmias (16.7%) has been reported in some patients. In the absence of coronary heart disease, the gradual increase of high-sensitivity cardiac troponin levels is a predictor of mortality.10 Cases of type I STEMI and fulminant myocarditis have also been reported.11

Most of the patients who develop complications are eligible for intensive therapy, and a high percentage of these may end up needing mechanical support of the ventricular function. The etiology of patients with cardiovascular complications can be coronary heart disease; this consideration will not be rare because the characteristics of patients more often affected are old age, overweight, high blood pressure, and diabetes mellitus. If the hypothesis of concomitant coronary heart disease is accepted there are two possible avenues: treat the case as that of a patient with NSTEMI and follow the corresponding algorithm or discard the presence of significant coronary heart disease using coronary computed tomography angiography.

In patients with severe pneumonia, myocardial damage, hemodynamic or electric instability, and suspicion of coronary heart disease, the medical team should decide on the adequacy (benefits exceeding risks, patients who can be saved) of transferring the patient to the cath lab or performing a coronary computed tomography angiography. In particular, the presence of left main coronary artery disease or disease of the proximal left anterior descending artery in a patient who can be saved supports the need to perform an urgent PCI (figure 3).

Figure 3. Diagnostic-therapeutic algorithm for the management of patients with COVID-19 or suspicion of COVID-19 infection with cardiovascular complications. B, benefits; CHD, coronary heart disease; CCTA, coronary computed tomography angiography; LAD, left anterior descending coronary artery; LMCA, left main coronary artery disease; R, risk; Tx, treatment.

VALIDITY OF RECOMMENDATIONS

The epidemiological model is totally unpredictable under the current circumstances; the rate of contagion, number of confirmed cases, and mortality rates are different across cities, regions, countries, and continents. However, estimates from the Mexican Ministry of Public Health suggest a peak of cases and more hospitalizations in the metropolitan area of Mexico City and main cities of the nation from May through August 2020. The flattening of the curve of infection will still take several months. No definitive projection on this regard can be given at the present time.

These recommendations will remain effective as necessary. They will be re-evaluated periodically together with the Mexican Ministry of Public Health to discuss the right time to go back to normal.

CONFLICTS OF INTEREST

None reported.

ACKNOWLEDGEMENTS

The authors wish to thank Dr. Jorge Gaspar Hernández, General Manager of the Ignacio Chávez National Institute of Cardiology for his remarks on this manuscript.

EDITOR’S NOTE

This document is subject to further iterations based on the evolution of the current COVID-19 pandemic. This manuscript has undergone a process of internal review of exceptional priority by the editorial staff due to the special interest of disclosing the information contained herein to the scientific community. The editors wish to thank Permanyer Publications for its collaboration and commitment for the quick publication of this document.

REFERENCES

INTRODUCTION

The current outbreak of COVID-19 has caused all healthcare providers have to rethink the indications for cardiac catheterization on an ongoing basis. The optimization of material and human resources, the prevention of contagions to healthcare providers and patients, and management during patient transfers makes it absolutely necessary to reformulate the protocols previously established. This consensus document has been agreed by the Spanish Society of Cardiology Working Group on Cardiac Catheterization and Interventional Cardiology (ACI-SEC) and the Spanish Society of Cardiology Working Group on Ischemic Heart Disease and Acute Cardiovascular Care. It includes indications to perform cardiac catheterizations under the current situation. It is difficult to foresee the evolution of this pandemic and its health impact, which will probably force us to readjust this document based on the particular situation and dynamic of each center. It is important to emphasize that when the actual situation is over, we recommend going back to the indications included in the clinical practice guidelines published by the European Society of Cardiology.1

In order to perform cardiac catheterizations our advice is to follow the recommendations on prevention and management included in the consensus document published by the ACI-SEC and the Heart Rhythm Association of the Spanish Society of Cardiology.2

ELECTIVE PROCEDURES

Indication for elective procedures in the catheterization laboratory should be based on individual assessments of the risk of contagion/benefit from the intervention ratio. In the current situation postponing all elective procedures seems the most reasonable thing to do to minimize the possibility of contagion of disease-free patients (and people they may have been in contact with) in a setting of high prevalence of COVID-19 infection such as hospitals. Similarly, performing right catheterizations during this pandemic is ill-advised.

If the cath lab has enough material and human resources, the non-emergent catheterizations of already hospitalized patients without suspicion of COVID-19 or COVID-19-negative patients may be an option to promote early discharges (ie, a study to characterize dilated cardiomyopathy in a patient admitted with an index episode of heart failure).

NON-ST-SEGMENT ELEVATION ACUTE CORONARY SYNDROME

Differential diagnosis

A key element to be taken into consideration when indicating a cardiac catheterization in a patient with acute coronary syndrome (ACS) is the high prevalence of heart disease in patients admitted due to COVID-19,3 the significantly high troponin levels (8% to 12% higher) seen in confirmed cases of COVID-19 but without ACS yet,4 and the possibility that myocarditis complicates the COVID-19 infection.5 This highlights the importance of clinical judgement before establishing a diagnosis of ACS/acute myocardial infarction. In general, in patients hospitalized due to COVID-19 infection who experience high cardiac enzyme levels of coronary origin and remain asymptomatic we recommend following a conservative approach. Coronary angiography should be spared for cases of high suspicion of high-risk ACS, medical treatment-resistant recurrent ischemia, and when the patient’s vital prognosis following the infection anticipates good prognosis.

NON-ST-SEGMENT ELEVATION ACUTE CORONARY SYNDROME

Figure 1 1 shows the approach suggested for patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). In patients hospitalized due to NSTEACS with suspicion of COVID-19 we recommend running the diagnostic test before performing the cardiac catheterization to assess the risk/benefit ratio of the procedure. The current clinical guidelines on revascularization recommend an early invasive strategy (less than 24 h) in patients with at least 1 criterion of high risk and in less than 72 h in patients with at least 1 criterion of intermediate risk.6. In most of the patients with NSTEACS this interval should be enough to confirm or discard the infection. The procedure should be postponed if the patient’s clinical situation allows it in cases where the diagnostic test is not available yet. On the contrary, in patients with NSTEACS but with persistent ischemia or high-risk criteria like recurrent angina, diffuse ST-segment changes suggestive of left main coronary artery or ventricular dysfunction performing the catheterization within the first 2 hours may be an option, taking the necessary protective measures to avoid transmitting the infection.

Figure 1. Algorithm for the management of elective patients and non-ST-segment elevation myocardial infarction (NSTEMI). ECG, electrocardiogram; PCI, percutaneous coronary intervention.

Patients negative for COVID-19 undergoing the procedure should be discharged early from the hospital.

In patients admitted to centers without a cath. lab. who need to be transferred, it is advisable, if possible, to follow a conservative approach and early discharge except for high-risk criteria or poor disease progression.

In selected patients with acute myocardial infarction—especially type 2 7— the conservative approach is the one recommended initially.

Revascularization in NSTEACS and multivessel disease

In patients with NSTEACS and multivessel disease and an indication for complete revascularization who remain hospitalized in centers where surgeries have been postponed, we recommend performing it within the same procedure to reduce hospital stay and avoid having to perform another procedure in the cath. lab.

ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION

The reperfusion treatment during the management of ST-segment elevation myocardial infarction (STEMI) of < 12 hour-duration since symptom onset should be primary percutaneous coronary intervention (pPCI) because it reduces the rates of mortality, reinfarction, stroke,1 and mechanical complications compared to fibrinolysis. Also, a significant percentage of patients undergoing pPCI can be discharged early and don’t require further invasive examinations which simplifies the management of these patients. This reduces the hospital stay and avoids collapsing the entire healthcare system. Nevertheless, during the COVID-19 pandemic the following key points should be taken into consideration:

• Due to the current care overload sustained by the ERs of our healthcare system, transfer times can take longer than usual in many cases.
• The transfer of patients with suspicion or confirmation of COVID-19 should take place safely and with infection under control. Also, after the transfer the ambulance should be properly disinfected. Therefore, the logistics required to guarantee safe transfers can also delay the entire process.
• Despite the preventive measures implemented to avoid transmitting the infection, the transfer of patients with an active infection for COVID-19 to a different center can infect the healthcare providers and, most important of all, other patients hospitalized and who are especially vulnerable to the disease.
• In patients already diagnosed with COVID-19 and in poor clinical state (especially patients hospitalized in intensive care units) with STEACS, repefusion treatment may yield no clinical benefits.

Reperfusion strategy

Figure 2 shows the management of STEMI. The ACI-SEC and the Spanish Society of Cardiology Working Group on Ischemic Heart Disease and Acute Cardiovascular Care recommend that the percutaneous coronary intervention should be the reperfusion strategy of choice in most cases. Fibrinolysis should be spared for cases diagnosed in non-PCI capable centers that meet one of the following requirements:

Figure 2. Algorithm for the management of patients with ST-segment elevation myocardial infarction (STEMI). AVB, atrioventricular block; FBL, fibrinolysis; PCI, percutaneous coronary intervention.

• Estimated time to the pPCI > 120 min.
• Patients who have tested positive to COVID-19 with poor clinical state that makes transfer difficult.
• Patients who have tested positive to COVID-19 with low hemorrhagic risk and symptoms of less than 3 hour-duration.

In cases where fibrinolysis may be an option, the lack of contraindications and the administration of the drug in less than 10 min from diagnosis should be guaranteed.1 Then, depending on the patient’s clinical state and the availability of beds in the ICU of the destination hospital, transfer to a center with cath. lab. capabilities may be considered. The rule of thumb here is to avoid transferring patients with confirmed reperfusion and good disease progression.

After the percutaneous coronary intervention, it is recommended that each patient be taken to their referring centers. However, the patients’ clinical situation and bed availability of each center should be individualized in each case.

Other considerations

As a general rule we recommend leaving the number of centers that are part of the infarction code program untouched. Although demand from out-of-hospital emergency medical services may change significantly during the COVID-19 pandemic, a hospitalized patient may have an indication for an urgent cardiac catheterization. In the current situation, transferring this patient to a different center may be more problematic than performing the procedure at the center where the patient is already hospitalized. Our recommendation here is that no PCI capable center should avoid treating infarctions.

Other clinical considerations:

• The diagnosis of STEMI in patients with complete left bundle-branch block is still complex to this day despite the use of different electrocardiographic criteria.8 Therefore, in patients with suspicion or confirmation of COVID-19 who require transfer for reperfusion we recommend agreeing on the diagnosis as much as possible to avoid unnecessary transfers.
• The management of patients with recovered sudden death without overt electrocardiographic criteria of STEMI is still controversial. Although a recent randomized clinical trial showed that these patients don’t benefit from an immediate coronary angiography,9 it is still being performed in most centers. However, due to their clinical situation—if infected—these patients are extremely prone to secreting microdroplets and infecting the healthcare providers. At the same time they are very vulnerable to infection if they are not already infected. For this reason, immediate PCIs are ill-advised in these patients.
• In patients with STEMI without cardiogenic shock and multivessel disease the overall recommendation is to perform a complete revascularization.10 However, in the current situation, we believe that the management of STEMI should be as simple as possible. In this sense, we believe that in most of these patients the management of non-culprit lesions should be postponed until the outbreak of COVID-19 is over. On the other hand, in patients with a clear need for complete revascularization at admission, we recommend the study of all lesions within the same procedure during the acute phase.

CARDIOGENIC SHOCK

In situations of acute coronary syndrome related cardiogenic shock, cardiac catheterization is indicated. The management of critically ill patients is especially complex because intubation, aspiration, and CPR maneuvers can prompt respiratory secretions in the form of aerosols and increase the exposure of the healthcare providers. All critically ill patients should be treated as patients with COVID-19.

The following key points should be taken into oconsideration:

• As in the rest of patients with cardiogenic shock, only the culprit vessel should be revascularized.11
• If intubation is necessary and possible, it should be performed before entering the cath. lab. and in the best conditions possible to comply with all COVID-19 prevention recommendations.
• Connection to a ventilator —a closed system— is recommended prior to manual ventilation with an ambu-bag. If ventilation with manual resuscitation is necessary, the use of high-efficiency particulate air (HEPA) filters between the tube and the bag is recommended.
• The extracorporeal membrane oxygenation (ECMO) machine used by the heart team should be purged at all times before the arrival of patients to reduce the possibility of infection and speed up the whole process. In patients with COVID-19 with cardiogenic shock, ECMO can be used as the first-line therapy compared to other devices like the Impella ventricular support system or the intra-aortic balloon pump counterpulsation.

STRUCTURAL HEART INTERVENTIONS

In general, all structural heart interventions should be postponed until the pandemic is under control. We should remember that most of these procedures require several days at the hospital, but at the same time the ICU/coronary unit beds may become necessary for patients with COVID-19. Also, in some cases structural heart interventions are performed under general anesthesia and intubation or on transesophageal echocardiography monitoring. All of them high-risk situations for the infection of patients and healthcare providers. On the other hand, patients undergoing structural heart interventions are often old and therefore especially susceptible to nosocomial infection due to COVID-19.

Other urgent procedures like aortic valvuloplasty or transcatheter aortic valve implantation in patients with angina at rest, recurrent syncope or refractory heart failure can be performed.

DRUGS

Regarding the drugs commonly used at the catheterization laboratory such as antithrombotic therapies, the recommendations are basically the same regardless of whether the patient has been infected with COVID-19 or not.

The medication to treat patients with COVID-19 may interact with the most common drugs currently used at the cath lab.12

Figure 3 shows the most commonly used drugs in cardiology both in the context of ACS and stable coronary artery disease.

Figure 3. Possible interactions between the most commonly used drugs in cardiology and the possible treatments used against COVID-19. ACE II, angiotensin-converting enzyme antagonists; ACEI, angiotensin-converting enzyme inhibitors; CCB, calcium channel blockers; DOAC, direct-acting oral anticoagulants; HFD, heart failure drugs.

Antiplatelet therapy

• Adiro: no evidence of significant interactions.
• Oral P2Y₁₂ platelet receptor antagonits: prioritize prasugrel. Concomitant treatment with lopinavir/ritonavir or darunavir/cobicistat increases the effect of ticagrelor and can reduce the effect of clopidogrel.
• Cangrelor: no evidence of significant interactions.
• Tirofiban: no evidence of significant interactions.

Anticoagulant drugs

• Unfractionated heparin: no evidence of significant interactions.
• Bivalirudin: no evidence of significant interactions.
• Enoxaparin: no evidence of significant interactions.
• Fondaparinux: no evidence of significant interactions.

Analgesics/sedatives

• Fentanyl/morphine: potential interactions; prioritize morphine.
• Midazolam: it should not be administered orally. It can be IV administered with special caution.

Inotropes and vasopressors

• Adrenaline: no evidence of significant interactions.
• Dobutamine: no evidence of significant interactions.
• Noradrenaline: no evidence of significant interactions.
• Dopamine: no evidence of significant interactions.

Other

• Nitroglycerin: no evidence of significant interactions.
• Verapamil: potential interactions. Administer and use with special caution and close monitoring.
• Furosemide: no evidence of significant interactions.

CONCLUSIONS

The current outbreak of COVID-19 has made us rethink the invasive approach to ischemic and structural heart disease. The recommendation of the Spanish Society of Cardiology Working Groups on Cardiac Catheterization and Interventional Cardiology and Ischemic Heart Disease and Acute Cardiovascular Care is to postpone all non-emergent procedures to avoid the infection of patients and healthcare providers and minimize the collapse of the healthcare system. However, the percutaneous coronary intervention should still be used for the management of ST-segment elevation myocardial infarction unless prescribed otherwise.

CONFLICTS OF INTEREST

The authors have declared no conflicts of interest regarding this manuscript. R. Moreno is associate editor of REC: Interventional Cardiology. The journal's editorial procedure to ensure impartial handling of the manuscript has been followed.

EDITOR'S NOTE

This manuscript has undergone an especially rapid internal review by the editorial team due to the strong interest indisseminating the information among the scientific community. The editors thank Permanyer Publications for their collaboration and commitment to the prompt publication of this document.

REFERENCES