202412151920
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Tags: Cardiology
Myocardial injury after non cardiac surgery
Up to 20% of adult patients have a postoperative elevated troponin after noncardiac surgery
Whether presenting with or without clinical symptoms, troponin elevation after noncardiac surgery has been shown to be independently associated with elevated risk of mortality, and cardiovascular complications for over a year after surgery
mortality is similar in symptomatic patients meeting the formal criteria for a diagnosis of myocardial infarction and in patients without any clinical symptoms
The American Heart Association lately defined MINS by at least one postoperative cTn concentration that exceeds the 99th percentile upper reference limit of the cTn assay
Troponin elevation should be due to a presumed ischemic mechanism (i.e., supply–demand mismatch or atherothrombosis), that is in the absence of overt nonischemic etiologies. Therefore, MINS does not include perioperative myocardial injury due to nonischemic causes such as sepsis, rapid atrial fibrillation, pulmonary embolism, or renal failure; nor does it include chronically elevated troponin concentrations
Based on the formal diagnostic criteria of MINS, postoperative MI represents a subset of MINS.
Specific troponin assay thresholds for the diagnosis of MINS are:
- any elevation ≥30 ng/l for Troponin 4th generation (TnT)
- For high sensitivity troponin T (hsTnT)
- ≥20 to <65 ng/l w/ an absolute change of ≥5 ng/l
- any elevation ≥65 ng/l
- any absolute change ≥14 ng/l.
Early landmark studies
Vision Phase 1
- International prospective cohort study
- Primary aim: determining the prognostic importance of postoperative troponin elevation
- Systematically troponin measurements at 6–12 h after surgery and on the first three postoperative days while patients remained hospitalized
- 15 133 patients involved, 4th-generation troponin T (nonhigh-sensitivity) was measured
- 8% of patients met MINS criteria
- Patients with MINS had an overall mortality at 30 days of 9.8% compared to 1.1% in patients without MINS
- Population-attributable risk for death was 34% (95% CI: 27, 4)
- Importantly, the vast majority (84%) of patients remained asymptomatic and only 42% of the patients fulfilled the formal criteria for MI
Vision Phase 2
- 21,842 patients had high-sensitivity troponin T (hsTnT) measured in the second phase
- Elevated postoperative hsTnT (i.e., 20 to <65 ng/l with an absolute change ≥5 ng/l compared to baseline, or hsTnT ≥65 ng/l) deemed to be ischemic in nature was associated with 30-day mortality (adjusted HR, 3.20; 95% CI, 2.37–4.32)
- 18% of patients had MINS, according to a definition of MINS based on these criteria for hsTnT elevation
The MANAGE trial is the first and only trial testing a pharmacological intervention specifically in patients with MINS
- 1754 patients
- 45 years old or older who underwent noncardiac surgery in 84 hospitals in 19 countries
- randomized within 35 days of MINS
- receive oral dabigatran 110 mg BID or placebo
- primary efficacy outcome
- (i.e. a composite of vascular mortality and nonfatal MI, nonhemorrhagic stroke, peripheral arterial thrombosis, amputation, and symptomatic venous thromboembolism)
- 11% in the dabigatran and 15% in the placebo groups,
- over a mean follow-up of 16 months after surgery
- (HR, 0.72; 95% CI, 0.55–0.93)
Thus, the MANAGE trial confirmed that patients with MINS have a poor long-term prognosis and established the efficacy and safety of a possible intervention for secondary major cardiovascular complications in these patients
Epidemiology & pathophysiology
More than 90% of MINS occurs during the initial 48 h after noncardiac surgery:
- roughly 40% on POD0
- 40% on POD1
- 15% on POD2
baseline CV risks
? Supply-demand mismatch > atherothrombotic event
Several intraoperative triggers of MINS have been identified:
- hemodynamic disturbances
- (perioperative hypotension and hypertension),
- tachycardia,
- anemia,
- hypothermia <35.5 °C,
- postoperative pain
Prevention
There is currently no known safe and effective method for prevention of perioperative MI and MINS, despite three large scale randomized trials investigating four separate preoperative interventions including
- beta-blockers (POISE),
- nitrous oxide (Enigma-2),
- aspirin, and clonidine (POISE-2)
Perioperative Ischemic Evaluation Study (POISE) randomized 8351 patients with known or suspected cardiovascular disease to extended-release metoprolol or placebo for inpatient noncardiac surgery, started 2–4 h before surgery and continued for 30 days after surgery. Metoprolol prevented nonfatal MI, with 152 (3.6%) patients given metoprolol having infarctions compared to 215 (5.1%) given placebo: OR 0.70 95% CI: 0.57–0.86, P = 0.0008). However, extended-release metoprolol was associated with higher incidences of strokes and deaths; and more frequent hypotension and bradycardia, perioperatively. Therefore, β blockers initiation in patients undergoing noncardiac surgery is currently not recommended
POISE-2 trial randomized 10 000 surgical patients to start or continue aspirin, or to placebo. The primary composite outcome including death or nonfatal MI occurred in 351 patients (7.0%) in the aspirin group, and 355 (7.1%) in the placebo group; 6.2% and 6.3%, respectively had MI, with no between-group difference. In contrast, patients assigned to aspirin had more major bleeding. According to a factorial design, in POISE-2 patients were also randomized to clonidine or placebo. Again, there was no difference in the primary outcome, nor in MI, with more patients in the clonidine group having bradycardia and hypotension
ENIGMA-2 trial randomized 7112 surgical patients with known or suspected cardiovascular disease to either nitrous oxide or nitrogen during anesthesia. The primary outcome was cardiac morbidity defined as a composite of death and cardiovascular complications (nonfatal MI, stroke, pulmonary embolism, or cardiac arrest) within 30 days of surgery. MI occurred in 283 (8%) of patients given nitrous oxide and in 296 (8%) of patients given nitrogen (relative risk 0.96 95% CI: 0.83, 1.12, P = 0.64).
Post-op surveillance
About 93% of MINS and 68% of MI are typically unrecognized without troponin screening.
Consequently, routine troponin screening is required, independent of any clinical symptoms
Routine troponin measurement is cost effective, although cost varies considerably from county-to-country and depends on the specific troponin assay used
Trending troponin (i.e., repeat troponin measurements) is fundamental to distinguish between acute and chronic troponin elevation, and to follow the evolution of troponin elevation
The peak of troponin elevation is of prognostic importance and may influence decisions regarding type and timing of cardiac testing and initiation of cardiovascular medications.
Guidelines
| AHA Guideline 2024 (perioperative cardiovascular management) | ESAIC Guideline 2023 (cardiac biomarkers) | ESC and ESAIC Guideline 2022 (cardiovascular assessment and management) | CCS Guideline 2017 (cardiac risk assessment and management) | |
|---|---|---|---|---|
| Definition of patients at risk and gap identifications | • “Patients with known cardiovascular disease, symptoms of cardiovascular disease, or age ≥65 years with cardiovascular risk factors” | • “Existence of cardiovascular risk factors (e.g. age ≥ 65 years) – known cardiovascular disease – presence of symptoms suggesting cardiovascular disease” • “The age cut-off for individuals (considered to be cardiovascularly healthy) benefiting from risk stratification work-out before noncardiac surgery needs to be evaluated” |
• “Patients with a baseline risk >5% for cardiovascular death or nonfatal myocardial infarction at 30 days after surgery (i.e., patients with an elevated NT-proBNP/BNP measurement before surgery or, if there is no NT-proBNP/ BNP measurement before surgery, in those who have an rCRI score >1, age 45–64 years with significant cardiovascular disease, or age 65 years or older)” | |
| Recommendation of postoperative MINS diagnostic | • In patients with … risk factors undergoing elevated risk noncardiac surgery, it may be reasonable to measure cTn at 24 and 48 h after surgery to identify myocardial injury” | • “Absolute increase of >99th upper reference limit (URL) of a high-sensitivity cardiac troponin assay” • “In these patients: exclusion of acute cardiac events (e.g. ECG, symptoms)” |
• “High awareness of perioperative cardiovascular complications, combined with surveillance for PMI (perioperative myocardial infarction/injury) in patients undergoing intermediate- or high-risk noncardiac surgery” • “PMI surveillance with hs-cTn T/I measurements before and serially after surgery (e.g. 24 and 48 h postoperatively)” • “Systematic PMI work-up is recommended to identify the underlying pathophysiology and define therapy” |
• “Daily troponin measurements for 48–72 h after noncardiac surgery in patients with a defined baseline risk” • Suggestion for “performing a postoperative ECG in the post anaesthesia care unit for patients” with the defined baseline risk • Suggestion for “shared-care management of patients” with the defined baseline risk |
| Recommendations of postoperative MINS management and gap identifications | • Patients with a postoperative troponin elevation (cut-off >99th percentile URL) should receive a physical examination and a 12-lead ECG. • “In patients who develop MINS, especially in those not previously known to have excess cardiovascular risk, outpatient follow-up is reasonable for optimization of cardiovascular risk factors” • “In patients who develop MINS, antithrombotic therapy may be considered to reduce thromboembolic events” |
• “Multidisciplinary approach when establishing cardiac troponin surveillance” • “For clinicians and patients who see benefit in reduction of major vascular complications, treatment with dabigatran twice daily may be considered” |
• “In patients with MINS and at low risk of bleeding, treatment with dabigatran 110 mg orally twice a day may be considered from around 1 week after noncardiac surgery” • “The optimal cardiac work-up and therapy for patients with PMI within and outside hospital settings need to be evaluated” |
• “Initiation of long-term statin and acetylsalicylic acid therapy in patients who suffer myocardial injury or myocardial infarction after noncardiac surgery” • “These patients should be followed-up by a medical specialist to monitor their status and optimize medications” |