Clinical Practice/Controversy: Selection of Reperfusion Therapy and Transfer Strategies for Patients with ST-Elevation Myocardial Infarction




Case Presentation


A 57-year-old man presents to a community hospital without capability for primary percutaneous coronary intervention (PPCI) in the early morning (4 am ) with a 1.5-hour history of severe chest pain. His medical history is significant for hypertension. His wife called 911, and at the time of first medical contact by paramedics, he was hemodynamically stable. On cardiac examination, his jugular venous pressure is elevated to 7 cm above the sternal angle, and a third heart sound is noted. Respiratory examination revealed basilar crackles in the lower lung fields. His electrocardiogram (ECG), which was recorded within 10 minutes of arrival, shows an anterior ST-elevation myocardial infarction (STEMI) with a large territory of myocardium at risk without baseline Q waves. Emergency medical service (EMS) transfer times to a PCI-capable hospital for PPCI are estimated to be 60 minutes, notwithstanding the harsh winter conditions. Tenecteplase (TNK) is readily available to administer at the presenting hospital site.




Introduction


In the current era of evidence-based therapy, morbidity and mortality from STEMI have remarkably declined (see Chapter 2 ). This trend has been accompanied by infarct size reduction and improvement in left ventricular function, largely mediated by timely and effective reperfusion therapy (see Chapter 13 ). Furthermore, enhanced public education leading to earlier patient presentation, rapid emergency response from well-trained and equipped paramedical personnel, improved treatment in the field, and application of the best reperfusion strategy for the right patient, at the right time, in the right place—all integrated with streamlined triage—have enhanced the care of STEMI patients (see Chapter 5 ).


The appreciation that early risk assessment informs diagnosis and guides use of appropriate contemporary pharmacologic and/or invasive strategies are key components of optimal patient-based care (see Chapter 11 ). However, in many jurisdictions, the prevailing clinical belief is that PPCI is not only the preferred reperfusion strategy as supported by a class I guideline recommendation (provided PPCI can be delivered expeditiously in a skilled 24/7 facility), but that it should be the only strategy. Although timely PPCI can now generally be accomplished in those patients presenting to a PPCI center, the feasibility of achieving this goal in the majority of STEMI patients (i.e., those presenting to a non–PCI-capable center, such as featured in the previously described case) is much more challenging. Placing the large majority of STEMI patients in the context of their geographic location, access to timely and expert 24/7 PPCI, transfer logistics, and the total elapsed ischemic time (defined as the delay from symptom onset to effective reperfusion therapy) unmasks the stark reality of significant management challenges. Because the key modulator of STEMI outcome is total ischemic time, yet widespread evidence exists that this recommended temporal window is consistently exceeded in a large number of patients transferred for PPCI, alternate strategies need to be explored. A pharmacoinvasive (PI) strategy has now emerged as a legitimate alternative.


Our aim in this chapter is to provide insights with regard to the selection of reperfusion strategies in STEMI patients who require transfer to a PCI-capable hospital. As first articulated in the 2004 American College of Cardiology Foundation (ACCF)/American Heart Association (AHA) STEMI guidelines, these insights align with the four key components of the recommended approach to STEMI, namely, evaluation of (1) baseline attributable risk from the STEMI, (2) the risk of fibrinolytic therapy, (3) the time from first medical contact, and (4) the time required to reliably achieve expert PPCI.




Elements that Influence Reperfusion Delay for Primary Percutaneous Coronary Intervention in Transfer Patients


Primary PCI performed expeditiously in a high-volume expertise center has excellent outcomes. However, patients without ready access to PCI sites are particularly sensitive to delays that may offset these clinical benefits ( Figure 14-1 ; see also Chapter 5 ).




FIGURE 14-1


Components of delays in transfer of ST-elevation myocardial infarction (STEMI) for primary percutaneous coronary intervention (PCI).

Patients presenting by ambulance are encouraged to bypass non-PCI hospitals and proceed directly to a PCI site. However, transfer logistics may still result in ambulance transport to a non–PCI-capable hospital, which then introduces further delays. ECG , Electrocardiogram; ED , emergency department; EMS , emergency medical services; FMC , first medical contact.


Patient Delay


Despite global public education efforts, many patients still do not seek medical attention for approximately 1 to 2 hours following symptom presentation. A profile of those patients who are most likely to delay activation of health care service has emerged and indicates they are more likely to be older adults, women, have diabetes, be African American, or of lower socioeconomic status. Clinical trial data from nearly 6000 STEMI patients who underwent PPCI within 6 hours of symptom onset emphasized the growing importance of older adults; whereas only 17% of this cohort was aged older than 65 years, they accounted for 64% of the deaths. An additional issue relates to patient choice of transportation to a health care facility. Because at least 50% of patients do not use the EMS system, they self-present as “walk-ins” to the nearest emergency room and are subject to further delays in diagnostic recognition and therapy (see Figure 5-12). Results from the Acute Coronary Treatment and Intervention Outcomes Network–Get With The Guideline (ACTION-GWTG) registry (>37,000 patients) found that only 60% of patients with STEMI activated EMS. The self-transport patients were more likely to be younger, men, hemodynamically stable, and have less co-morbid conditions. Longer ischemic times and extended treatment delays were noted, subjecting these patients to adverse outcomes.


Prehospital System Delay


In patients who directly activate EMS, continued challenges exist regarding transport to PCI-capable hospitals. Efforts have been made to bypass non-PCI sites and proceed to regional STEMI referral centers; however, 80% of such patients still do not achieve PPCI within 90 minutes (see Chapter 5 ). Despite major national efforts to reduce treatment times for PPCI, an analysis of more than 12,000 STEMI patients in the ACTION-GWTG registry (including patients from the “Mission: Lifeline” program [2008 to 2011]) found emergency department bypass occurred infrequently (10.5%) and occurred primarily during usual working hours only. Shorter first medical contact to device times were noted in patients who bypassed the emergency department, but these shorter times were associated with marginal improvements in adjusted in-hospital mortality (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.45 to 1.03; P = .07).


In a key observational registry of 6209 Danish patients with STEMI transported by EMS for PPCI (35% who were transferred prehospital direct to a PCI center, with the remaining patients transferred from a non–PCI-capable hospital), long-term mortality (median 3.4 years, interquartile range [IQR], 1.8 to 5.2) increased with system delays (see Figure 5-9 ). Hence, the impact of total ischemic time is critically important and prognostically relevant as represented by the system delay (i.e., first medical contact to procedure) when considering transfer for PPCI. These data are especially noteworthy because (1) they demonstrate the inability to provide timely PPCI for most of the patients in the small country of Denmark, where drive times are short and PPCI facilities are abundant; (2) Denmark has substantial experience in conducting trials of transfer strategies that strongly influenced the movement towards PPCI; and (3) short-term mortality (in-hospital, 30 day, or even 1 year) is a blunt instrument to assess the longer term implications of delayed reperfusion. This issue is explored further in the section on Future Perspectives.


Interhospital System Delay


In the United States, most STEMI patients do not present to a PCI-capable site because the majority (approximately 80%) of health care institutions across the country are community hospitals without PPCI capability. For those patients who self-present to a non–PCI-capable facility and who require transfer, door-to-balloon times remain well above the targeted recommendation (transfer door to balloon ≤90 minutes) to improve timely access to care (7.6% in 2007 to 18.7% in 2009). Using the National Cardiovascular Data Registry (NCDR)-CathPCI Registry data between 2005 and 2007, Wang and colleagues assessed more than 115,000 STEMI patients who underwent PPCI at 790 hospitals across the United States. Of these, 25% of patients presented to non-PCI hospitals. Treatment of STEMI patients who had to be transferred significantly exceeded the guideline limits, with longer median door-to-balloon times than those who presented directly to PPCI centers (median 149 minutes vs. 79 minutes). Only 10% of transfer patients achieved a door-to-balloon time within 90 minutes of presentation. The ACTION Registry–GWTG reviewed more than 20,000 fibrinolysis-eligible STEMI patients who presented to a non–PCI-capable center with interhospital drive times of 30 to 120 minutes. Of these, most patients (70.5%) were transferred to a PCI-capable facility for PPCI. Disappointingly, only 51.3% were able to achieve ACC/AHA guideline-recommended first medical contact to reperfusion time within 120 minutes. Figure 14-2 highlights the proportion of patients who achieved successful mechanical reperfusion times, stratified according to drive times for transfer. Of note, only 52.7% of patients with a drive time longer than 60 minutes received fibrinolysis (see Figure 14-2 ). Hence, this persistent delay in achieving timely PPCI in those patients transferred from other institutions is still unacceptably high and does not meet current guideline metrics for STEMI.




FIGURE 14-2


Proportion of door-to-balloon (DTB) times ≤120 minutes ( blue bars ) achieved versus percentage of patients with fibrinolysis administered ( red bars ) stratified by interhospital drive time among patients requiring transfer for ST-elevation myocardial infarction (STEMI).

A report from the US National Cardiovascular Data Registry.

(Data from Vora AN, et al: Fibrinolysis use among patients requiring interhospital transfer for ST-segment elevation myocardial infarction care: A report from the US National Cardiovascular Data Registry. JAMA Intern Med 175:207–215, 2015.)


Door-in-Door-out Time


Because of the delays that occur at the referral site (i.e., awaiting transport and emergency department delay), increased efforts have been initiated to reduce the delay between arrival to a non-PCI hospital and transfer to a PCI facility. Termed as door-in-door-out (DIDO) time, the 2008 ACC/AHA Clinical Performance Measures for Acute Myocardial Infarction recommended a DIDO time of less than 30 minutes. This quality metric was evaluated in nearly 15,000 STEMI patients who participated in the NCDR ACTION-GWTG registry who were initially seen in a non–PCI-capable hospital and subsequently transferred. The median DIDO was 68 minutes (IQR 43 to 120 minutes), with a DIDO time of ≤30 minutes achieved in only 11% of patients (see Figure 5-10 ). Predictors of longer DIDO times included older age, female gender, off-hour presentation, and non-EMS arrival to the referring hospital.


Mode of Transfer


Transfer times are also dependent on geographic constraints. Even in a well-developed STEMI transfer system of care, first door-to-device (D2D) times of 90 to 120 minutes can only be achieved for those hospitals located within a 30-minute transfer drive time (median D2D time of 93 minutes for drive times ≤30 minutes, 117 minutes for drive times of 31 to 45 minutes, and 121 minutes for drive times >45 minutes). Air transport has been explored to help expedite transport of STEMI patients, but without consistent success. In a study of 140 patients transported from 16 hospitals by helicopter service within a 150-mile radius to 6 PCI-capable centers in Cincinnati, Ohio for PPCI, 111 ultimately underwent PCI, with 97% of cases exceeding a D2D time of 90 minutes (median 131 minutes). Compared with ground transport, helicopter transport delayed D2D times irrespective of the distance-associated transfer drive time (helicopter transfer median D2D time 125 minutes for drive times of 31 to 45 minutes and 138 minutes for drive times >45 minutes).


Primary Percutaneous Coronary Intervention Center Logistics Delay


Even if rapid transfer of patients to a PPCI-capable facility can be achieved, obstacles to delivering timely PPCI still exist. In an observational study of approximately 83,000 STEMI patients in the NCDR CathPCI Registry (2009 to 2011), delays to PPCI occurred in 14.7% of patients because of informed consent, concerns about obtaining vascular access, and difficulties crossing the infarct-related artery. Not surprisingly, the in-hospital mortality was substantially higher in patients with a delay compared with patients without a PPCI center logistics delay even after adjustment for baseline risk (15.1% vs. 2.5%; P <.01). This observation reinforces the importance of the skill set developed in a high-volume experienced PPCI center and constitutes a cautionary reminder about the propensity to build low-volume PPCI centers in areas already well served by such facilities. Strategies to develop systems to minimize such delays in an ideal STEMI system are discussed in detail in Chapter 5 .




Choice of Reperfusion Strategy in Transfer Patients


A “one-size-fits-all” approach does not adequately address the needs of patients with STEMI who require transfer to a health care facility, whether it be in an ambulance or to a community hospital. Although the particular approach requires sensitivity and understanding of regional realities and resources, the time-honored admonition formulated first in the 2004 ACC/AHA STEMI guidelines remains central to best practice, that is, “the appropriate and timely use of some form of reperfusion therapy is likely more important than the choice of therapy. Greatest emphasis is to be placed on the delivery of reperfusion therapy to the individual patient as rapidly as possible.” For that reason, application of evidence-based reperfusion choices to promote and sustain high-quality reperfusion, limit myocardial damage, prevent unfavorable left ventricular remodeling, and reduce mechanical complications of myocardial infarction (MI) are key responsibilities of the front-line clinician (see Chapter 13 ). This responsibility to the STEMI patient is best discharged by integrating the factors illustrated in Figure 14-3 .




FIGURE 14-3


The four key factors to be considered when selecting a reperfusion strategy in ST-elevation myocardial infarction (STEMI) patients who require transfer to a percutaneous coronary intervention (PCI)-capable hospital.


Influence of Index ST-Elevation Myocardial Infarction Risk


Because baseline risk strongly intersects with time from symptom onset to reperfusion in modulating reperfusion strategies, an appreciation for the wide spectrum of STEMI risk is paramount. Morrow and colleagues demonstrated that most of the STEMI patients in the National Registry of Myocardial Infarction (NRMI)-3 registry were at a low risk (i.e., Thrombolysis In Myocardial Infarction [TIMI] risk score <5). Ten years later, this finding was substantiated by registry data in Belgium that demonstrated that only 18.5% of patients had a high-risk TIMI profile. Although no difference in survival between those treated with PPCI versus fibrinolysis was observed in most of the patients, that is, those at low risk (0.3% vs. 0.4%; adjusted P = .60) or intermediate risk (2.9% vs. 3.1%; adjusted P = .30), in-hospital survival was improved with PPCI compared with fibrinolysis in the TIMI high-risk patients (23.7% vs. 30.6%; adjusted P = .03). These data are well aligned with the 3-year follow-up from the Danish Multicentre Randomized Study of Fibrinolytic Therapy vs. Primary Angioplasty in Acute Myocardial Infarction (DANAMI)-2 trial, which stratified STEMI patients according to baseline risk using the TIMI risk score (low risk TIMI 0 to 4; high risk TIMI ≥5). Only high-risk patients experienced a survival benefit from PPCI compared with fibrinolysis (25.3% vs. 36.2%; P = .02) ( Figure 14-4 ), whereas, once again, most of the low-risk STEMI patients (74%) showed no survival benefit with PPCI (8.0% vs. 5.6%).




FIGURE 14-4


Three-year follow-up data from DANAMI-2.

Mortality outcomes partitioned according to baseline Thrombolysis In Myocardial Infarction (TIMI) risk score. Note for the 25% of patients with TIMI risk ≥5, primary percutaneous coronary intervention (PCI) demonstrated an advantage, whereas for 75% of the population, the reverse tended to be true. Patients with TIMI risk 0 to 4 are indicated with dotted lines , those with TIMI risk ≥5 are indicated with solid lines .

(Adapted from Thune JJ, et al: Simple risk stratification at admission to identify patients with reduced mortality from primary angioplasty. Circulation 112:2017–2021, 2005; Figure 1 .)


Although the high-risk TIMI score patients derived clinical benefit with PPCI, other high-risk cohorts deserve further clarification. In patients who presented with hemodynamic compromise, secondary analyses from the Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock (SHOCK) trial demonstrated benefit with early coronary angiography and emergent revascularization (PCI or coronary artery bypass graft [CABG]) compared with medical stabilization and delayed invasive assessment. Approximately 50% of the patients randomized to emergent revascularization received fibrinolysis before the procedure. In the SHOCK Trial Registry, a combination of fibrinolytic therapy and intra-aortic balloon pump counterpulsation appeared to reduce in-hospital mortality. Thus, for hospitals without revascularization capabilities and long transfer times to a PCI-capable hospital, fibrinolysis may be a reasonable alternative with immediate transfer to a PCI-capable site.


Notwithstanding the key influence of baseline risk, none of the previous studies addressed the intersection between this key variable and total ischemic time. Arguably, the early presenting patient with a large territory of myocardium at risk has the highest mortality compared with the later presenting patient who has outlived the time period with the greatest risk of death. This survival bias effect was well demonstrated in the prefibrinolytic era, in which 88% of patients who presented within 1 hour of symptoms (compared with 43% of patients who presented after 1 hour of symptoms) died either before or during hospital admission. Hence, there is growing acceptance from previous registry data of the need to also account for the myocardial territory at risk in choosing a reperfusion strategy and a greater imperative for shorter delay from first medical contact to reperfusion in early presenting (<2 to 3 hours) patients. Based on the NRMI registry analysis of Pinto and colleagues, a young patient with an anterior STEMI (i.e., a large territory of myocardium at risk) who presents early with symptoms should be considered for fibrinolysis because of the equipoise with PPCI ( Figure 14-5 ). In this regard, the 2012 European Society of Cardiology (ESC) STEMI guidelines indicate a preferred target of less than 90 minutes from first medical contact for reperfusing such patients. This recommendation has now been supported by an analysis of the Strategic Reperfusion Early After Myocardial Infarction (STREAM) trial, which randomized patients to a PI versus PPCI strategy in early presenting STEMI patients and demonstrated similar rates of the composite of death, shock heart failure, and reoccurrence of MI between randomized treatment groups irrespective of ischemic area at risk (defined by the baseline electrocardiogram).




FIGURE 14-5


Influence of infarct location, age, and ischemic time on percutaneous coronary intervention (PCI)-related delay in which PCI and fibrinolytic mortality are equal.

Note the narrow PCI-related delay window for a young patient with an anterior (Ant) ST-elevation myocardial infarction. DB-DN , Door-to-balloon, door-to-needle time.

(From Pinto DS, et al: Hospital delays in reperfusion for ST-elevation myocardial infarction: implications when selecting a reperfusion strategy. Circulation 114:2019–2025, 2006; Figure 4 .)


Influence of the Risk of Fibrinolysis


A cardinal decision point in the choice of acute reperfusion therapy is prompt evaluation of the risk of fibrinolysis. Contraindications to fibrinolysis, including a heightened risk of intracranial hemorrhage (ICH), are summarized in Chapter 15 (see Table 15-5 ). The overall incidence of ICH with contemporary fibrinolysis agents is approximately 1% and must be incorporated into the risk–benefit analysis of pharmacologic reperfusion using predictors identified from previous fibrinolytic studies (see Chapter 15 ). For example, in the Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries (GUSTO)-1 trial, patients with a previous stroke or transient ischemic attack were at heightened risk of ICH (5% to 7%). Independent predictors of ICH formulated from more than 30,000 Medicare patients in the Cooperative Cardiovascular Project who received fibrinolytic therapy between 1994 and 1995 (overall risk of ICH was 1.43%) were incorporated into a risk model that revealed a range from 0.69% (risk score 0 to 1) to 4.11% (risk score ≥5) ( Table 14-1 ).



TABLE 14-1

Risk Score for Predicting Intracranial Hemorrhage with Fibrinolysis








































Risk Factor Risk Score Rate of ICH (%)
Age ≥75 yrs 0–1 0.69
Black race 2 1.02
Female gender 3 1.63
History of stroke 4 2.49
SBP ≥160 mmHg ≥5 4.11
Weight ≤65 kg for women or ≤80 kg for men
INR >4 or PT >24
Use of alteplase

ICH , Intracranial hemorrhage; INR , international normalized ratio; PT , prothrombin time; SBP , systolic blood pressure.

Each risk factor is worth 1 point if present, 0 points if absent.



Table 15-5 distinguishes between absolute and relative contraindications; in the former, PPCI is the only legitimate option, whereas in the latter situation, the use of fibrinolytic therapy needs to be weighed against the risk of the MI and the cost of a major delay to PPCI. The risk of non-ICH bleeding should also be considered, but its overall incidence is comparable or less than that found with PPCI.


However, even when patients are considered eligible for fibrinolysis, a preoccupation with door-to-balloon times and PPCI tends to dominate, which could result in unforeseen consequences. In a large NCDR registry study of 22,481 STEMI patients who were eligible for fibrinolysis, who presented to a non-PCI hospital, and who required transfer, only 29.5% received fibrinolytic therapy. Moreover, the door-to-needle times appeared to be longer in high-volume PPCI facilities, which suggested “skill atresia” for a simple bolus fibrinolysis approach. This fundamental skill set, particularly among young clinicians (many of whom have never administered fibrinolytic therapy for STEMI), is waning, but it is imperative to maintain competence and proficiency in treating all STEMI patients.


Influence of Ischemic Time


From the original canine experiments of Jennings and Reimer, ischemic necrosis begins in the subendocardium within 20 minutes of coronary occlusion and proceeds in a transmural wavefront of cell death, culminating within 3 to 6 hours. Reperfusion within the first hour salvages almost two-thirds of the myocardium at risk, but thereafter salvage abruptly declines. Moreover, the Fibrinolytic Therapy Trialists’ (FTT) Collaborative Group demonstrated maximum survival benefit (35-day mortality) in patients who received fibrinolytic therapy within 60 minutes of symptom onset (see Figure 13-3 ). Cardiac magnetic resonance findings by Francone and colleagues examined different total ischemic time intervals to PPCI and found that myocardial salvage markedly decreased in tandem with increased microvascular obstruction when symptom onset to balloon time exceeded 90 minutes ( Figure 14-6 ). Hence, the success of either form of reperfusion therapy is unequivocally time dependent.




FIGURE 14-6


Relationship between ( A ) myocardial salvage and ( B ) microvascular obstruction, with time from symptom onset to reperfusion in 70 consecutive patients with first ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) within 12 hours of symptom onset at a single center. As time to PPCI increases beyond 90 minutes, the extent of myocardial salvage declines and frequency of microvascular obstruction rises.

(Adapted from Francone M, et al: Impact of primary coronary angioplasty delay on myocardial salvage, infarct size, and microvascular damage in patients with ST-segment elevation myocardial infarction: Insight from cardiovascular magnetic resonance. J Am Coll Cardiol 54:2145–2153, 2009.)


Early Presenters


The impact of ischemic time on choice of reperfusion strategy has largely been overlooked in contemporary management. By exploring the temporal relationships between fibrinolysis and PPCI, the slope of efficacy over time is shallower for PPCI compared with fibrinolysis; this relationship is related in part to the more successful pharmacologic lysis of younger thrombi versus the more consistent, less time-sensitive PPCI efficacy of opening occluded vessels. In a meta-analysis of more than 50,000 patients who received fibrinolysis for STEMI, the benefit was greatest in those patients who received therapy within 2 hours; thereafter, a linear decline in mortality was noted. In a combined analysis of the Comparison of primary Angioplasty and Pre-hospital fibrinolysis In acute Myocardial infarction (CAPTIM) and Which Early ST-Elevation Myocardial Infarction Therapy (WEST) trials, which were aimed at early treated patients who presented within 2 hours of symptom onset, a temporal interaction demonstrated that those who received early fibrinolysis (and frequent timely coronary co-intervention) demonstrated improved 1-year survival compared with PPCI (2.8% vs. 6.9%; HR 0.43; 95% CI, 0.20 to 0.91; P = .021). This reinforced the importance of attenuating total ischemic time in early presenting patients with STEMI. This finding may be related to a lesser frequency of cardiogenic shock and heart failure, and a greater propensity for “aborting” MI (see Figure 13-3 ).


In the Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT)-3 fibrinolytic trial, one in four patients treated within the first hour of symptom onset exhibited complete resolution of their initial ST elevation with minimal or no myocardial necrosis. This pattern was also evident in a prespecified analysis from the STREAM trial (patients were randomized <3 hours after symptoms), in which aborted MI was more frequent with early fibrinolysis compared with PPCI (11.1% vs. 6.9%; P <.01). Aborted MI was associated with improved clinical outcomes at 30 days (death, cardiogenic shock, congestive heart failure, and/or recurrent MI: 7.0% vs. 12.5%; P = .042); the patients who had early fibrinolysis aborted had a lower composite endpoint (5.1% vs. 12.0%; P = .038). There was good temporal alignment between the ischemic time, experimental myocardial salvage (see Figure 14-6 ), and lives saved from early fibrinolytic therapy and a propensity for aborted MI with prompt reperfusion therapy (see Figure 13-3 ).


Late Presenters


Those STEMI patients who present more than 3 to 4 hours after symptom onset fall into a time period with a shallower slope of the survival curve versus the time-to-reperfusion curve for fibrinolytic therapy; therefore, the impact of total ischemic time may be less relevant. These patients should be especially considered for PPCI because of the improved efficacy of reperfusion. In many STEMI patients, the time of symptom onset is difficult to ascertain and largely dependent on patient recollection; this challenge is especially true in older patients, women, patients with diabetes, and heart failure patients. Assessment of the baseline Q wave in the distribution of the baseline ST elevation may provide additional insight into the status of MI evolution, and has been shown to be associated with reduced myocardial perfusion and adverse clinical outcomes, surpassing the time of symptom onset as a prognostic marker. This relationship appears to be especially relevant to women with STEMI. Hence, when a Q wave is already formed, less potential for salvaging myocardium is expected (despite total ischemic time), and consideration for PPCI with a transfer to a PCI-capable facility may be warranted. In this respect, it is of interest to compare the ECG in our Case Presentation with those in two patients who presented early with anterior MI (∼2 hours); despite similar times and extent of ST elevation, there was a well-formed Q wave on the baseline ECG from the patient on the right ( Figure 14-7 ). The additional insight provided by the ECG into the state of evolution of the STEMI may be useful in modulating the reperfusion pathway.




FIGURE 14-7


Twelve-lead electrocardiograms from two anterior ST-elevation myocardial infarction (STEMI) patients presenting at the same time from symptom onset (2 hours).

Note the patient in the left panel has no baseline Q-wave, whereas the patient on the right already has a well-formed Q-wave.


Influence of Transfer Time to Primary Percutaneous Coronary Intervention versus Fibrinolysis


Several randomized trials have suggested the benefit of a transfer strategy for PPCI in patients who present to a non-PCI capable hospital. The PRimary Angioplasty in patients transferred from General community hospitals to specialized PTCA Units with or without Emergency thrombolysis (PRAGUE)-2 trial randomized 850 patients with STEMI in the Czech Republic to either in-hospital fibrinolysis (with PCI according to routine clinical indication) or immediate transfer for PPCI (see Figure 5-e7 ). The time from randomization to balloon in the PCI group was remarkably short (97 ± 27 minutes), suggesting efficient transport with minimal system delays. In this context, a trend toward reduced 30-day mortality was observed with a transfer PPCI approach compared with fibrinolysis (6.8% vs. 10.0%; P = .12). However, in patients who presented early (<3 hours), no difference in mortality was seen, taking into consideration the use of a nonfibrin specific agent (streptokinase) (7.3% vs. 7.4%).


Similarly, the Danish DANAMI-2 investigators randomized 1771 patients to early fibrinolysis versus PPCI, and in the 1129 patients randomized at a non–PCI-capable hospital, clinical benefit (death, clinical evidence of reinfarction, or disabling stroke) was seen with a transfer PPCI approach (8.5% vs. 14.2%; P = .002) (see Figure 5-e8 ). Again, system delays were minimal in these patients because randomization to treatment was a median of 90 minutes (IQR, 74 to 108 minutes). Furthermore, benefits were mainly driven by a reduction in reinfarction (1.6% vs. 6.3%; P <.001), in which routine coronary angiography for fibrinolysis patients was not mandated (and repeat fibrinolysis was recommended for failed reperfusion). No differences in death (6.6% vs. 7.8%; P = .35) or stroke (1.1% vs. 2.0%; P = .15) were observed. As described previously, and unlike subsequent “real-world” registry data that examine transfer times, the system delays were short in both these studies, which contributed to the success of PPCI for those patients who presented to a non–PCI-capable hospital. More specifically, it should be noted that there was a remarkably short time difference in the initiation of reperfusion therapy (28 minutes) between the fibrinolytic strategy and PPCI in DANAMI 2.


Most recently, the STREAM trial (n = 1892) tested an early fibrinolysis strategy coupled with timely co-intervention (PI approach) compared with PPCI in patients who presented within 3 hours of symptom onset who were not able to obtain timely PCI within 60 minutes (most commonly because of the need for transfer to a PCI-capable facility). No difference in the 30-day primary endpoint of death, shock, congestive heart failure, or reinfarction was seen between the two groups (12.4% for PI vs. 14.3% for PPCI; relative risk [RR], 0.86; 95% CI, 0.68 to 1.09). In addition, no difference in mortality was noted at 1 year. Hence, this study, which amended the fibrinolytic dose by one-half in patients aged 75 years or older after 20% of patients were enrolled because of safety concerns, provided support for using the PI approach as a legitimate alternative for the large cohort of STEMI patients who cannot undergo timely PCI. It is especially noteworthy that the STEMI patients were reperfused much earlier than in many other STEMI randomized studies during the time when opportunities for salvage were most opportune ( Figure 14-8 ).


Aug 10, 2019 | Posted by in CARDIOLOGY | Comments Off on Clinical Practice/Controversy: Selection of Reperfusion Therapy and Transfer Strategies for Patients with ST-Elevation Myocardial Infarction

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