The mechanism of supply-demand imbalance and clinical outcomes in patients with type 2 myocardial infarction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Bularga ◽  
A Anand ◽  
F.E Strachan ◽  
K.K Lee ◽  
S Stewart ◽  
...  

Abstract Background Type 2 myocardial infarction is common and associated with substantial risk of adverse clinical outcomes, worse than type 1 myocardial infarction, with as few as 30% of patients still alive at five years. However, this broad diagnostic term encompasses multiple mechanisms of supply-demand imbalance, which may be associated with different risks of adverse outcomes. Purpose We aimed to assess the prevalence and clinical outcomes of different mechanisms of supply-demand imbalance related to survival in the High-STEACS (High-Sensitivity Troponin in the Evaluation of patients with Acute Coronary Syndrome) randomised controlled trial. Methods The High-STEACS trial was a stepped wedge cluster randomised controlled trial in ten hospitals across Scotland, including 48,282 consecutive patients with suspected acute coronary syndrome. The diagnosis was adjudicated according to the Fourth Universal Definition of Myocardial Infarction. In patients with type 2 myocardial infarction, we prospectively adjudicated the cause for supply demand imbalance. Linkage of electronic healthcare records was used to track investigation, treatments and clinical outcomes. We used the Kaplan-Meier method, the log rank test and cox regression models adjusted for age, sex, renal function and co-morbidities to evaluate the risk of future all-cause mortality between categories. Results We identified 1,121 patients with type 2 myocardial infarction (age 74- ± 14, 55% female). At one year, death from any cause occurred in 23% (258/1,121) of patients. The most common reason for supply-demand imbalance was tachyarrhythmia in 55% (616/1,121), followed by hypoxaemia in 20% (219/1,121) of patients. Tachyarrhythmia was associated with reduced future risk of all-cause mortality (adjusted HR 0.69, 95% CI 0.43–1.09), similar to those with type 1 myocardial infarction. Comparatively, patients with hypoxaemia appeared at highest risk (adjusted HR 1.75, 95% CI 1.09–2.80). Conclusion The mechanism of myocardial oxygen supply-demand imbalance is associated with future prognosis, and should be considered when risk stratifying patients with type 2 myocardial infarction. Supply-demand imbalance survival Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): British Heart Foundation

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Bularga ◽  
A Anand ◽  
F E Strachan ◽  
K K Lee ◽  
S Stewart ◽  
...  

Abstract Background Guidelines acknowledge the emerging role of high-sensitivity cardiac troponin (hs-cTn) assays for the risk stratification and rapid rule-out of myocardial infarction, but multiple approaches have been described. We previously demonstrated the utility of a single hs-cTnI concentration <5 ng/L at presentation to risk stratify patients with suspected acute coronary syndrome (ACS). Purpose To assess the safety and efficacy of a hs-cTnI concentration <5 ng/L at presentation in consecutive patients included in the High-STEACS (High-SensitivityTroponin in the Evaluation of patients with Acute Coronary Syndrome) randomised controlled trial. Methods The High-STEACS trial was a stepped wedge cluster randomised controlled trial in ten hospitals across Scotland that included 48,282 patients in whom high-sensitivity cardiac troponin was requested by the attending clinician for evaluation of suspected ACS. Patients with ST-segment elevation myocardial infarction (STEMI) were excluded. We evaluated the negative predictive value (NPV) and sensitivity of a presentation hs-cTnI <5 ng/L for a composite outcome of type 1 myocardial infarction, or subsequent type 1 myocardial infarction or cardiac death at 30 days. To assess safety, we report the one-year risk of type 1 myocardial infarction or cardiac death. To assess efficacy, we report the proportion of patients with cardiac troponin <5 ng/L at presentation. Results We included 47,101 consecutive patients in the analysis (mean 61±17 years old, 47% female). Of these patients, 27,500 (58%) had a cardiac troponin <5 ng/L at presentation. Overall, 4,313/47,101 (9%) patients had a composite outcome at 30 days, but the event rate was only 0.4% in those with troponin <5 ng/L (98/27,500). The NPV for the composite outcome in those <5 ng/L was 99.7% (95% confidence intervals [CI] 99.6–99.7) and the sensitivity was 98.0% (95% CI 97.6–98.4). In those without evidence of myocardial injury at presentation (hs-cTnI <99thcentile), type 1 myocardial infarction or cardiac death at one year occurred in 197 (0.7%) patients with cardiac troponin <5 ng/L, compared to 647 (5.5%) of those ≥5 ng/L. The NPV was unchanged across all age groups, although efficacy fell as fewer older patients had hs-cTnI concentrations below the risk stratification threshold (see Figure). Conclusion A hs-cTnI concentration <5 ng/L at presentation identifies the majority of patients with suspected ACS as low-risk of early or late cardiac events. Although the proportion identified as low risk is reduced in older populations, the safety of this risk stratification approach is maintained across patients of all ages. Acknowledgement/Funding British Heart Foundation


Author(s):  
Ryan Wereski ◽  
Dorien M. Kimenai ◽  
Caelan Taggart ◽  
Dimitrios Doudesis ◽  
Kuan Ken Lee ◽  
...  

Background: Whilst the 99th percentile is the recommended diagnostic threshold for myocardial infarction, some guidelines also advocate the use of higher troponin thresholds to rule-in myocardial infarction at presentation. It is unclear whether the magnitude or change in troponin concentration can differentiate causes of myocardial injury and infarction in practice. Methods: In a secondary analysis of a multi-centre randomized controlled trial, we identified 46,092 consecutive patients presenting with suspected acute coronary syndrome without ST-segment elevation myocardial infarction. High-sensitivity cardiac troponin I concentrations at presentation and on serial testing were compared between patients with myocardial injury and infarction. The positive predictive value (PPV) and specificity were determined at the sex-specific 99th percentile upper reference limit (URL), and rule-in thresholds of 64 ng/L and 5-fold of the URL for a diagnosis of type 1 myocardial infarction. Results: Troponin was above the 99th percentile in 8,188 (18%) patients. The diagnosis was type 1 or type 2 myocardial infarction in 50% and 14%, and acute or chronic myocardial injury in 20% and 16%, respectively. Troponin concentrations were similar at presentation in type 1 (median [25th percentile - 75th percentile] 91 [30-493] ng/L) and type 2 (50 [22-147] ng/L) myocardial infarction, and in acute (50 [26-134] ng/L) and chronic (51 [31-130] ng/L) myocardial injury. The 99th percentile and rule-in thresholds of 64 ng/L and 5-fold URL gave a PPV of 57% (95% confidence interval [CI] 56-58%), 59% (58-61%) and 62% (60-64%), and a specificity of 96% (96-96%), 96% (96-96%) and 98% (97-98%), respectively. The absolute, relative and rate of change in troponin concentration was highest in patients with type 1 myocardial infarction (P<0.001 for all). Discrimination improved when troponin concentration and change in troponin were combined compared to troponin concentration at presentation alone (area under curve, 0.661 [0.642-0.680] versus 0.613 [0.594-0.633]). Conclusions: Although we observed important differences in the kinetics, cardiac troponin concentrations at presentation are insufficient to distinguish type 1 myocardial infarction from other causes of myocardial injury or infarction in practice and should not guide management decisions in isolation. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01852123


2018 ◽  
Vol 128 (6) ◽  
pp. 1084-1091 ◽  
Author(s):  
Mohammad A. Helwani ◽  
Amit Amin ◽  
Paul Lavigne ◽  
Srikar Rao ◽  
Shari Oesterreich ◽  
...  

Abstract Background The objective of this investigation was to determine the etiology of perioperative acute coronary syndrome with a particular emphasis on thrombosis versus demand ischemia. Methods In this retrospective cohort study, adult patients were identified who underwent coronary angiography for acute coronary syndrome within 30 days of noncardiac surgery at a major tertiary hospital between January 2008 and July 2015. Angiograms were independently reviewed by two interventional cardiologists who were blinded to clinical data and outcomes. Acute coronary syndrome was classified as ST–elevation myocardial infarction, non–ST–elevation myocardial infarction, or unstable angina; myocardial infarctions were adjudicated as type 1 (plaque rupture), type 2 (demand ischemia), or type 4b (stent thrombosis). Results Among 215,077 patients screened, 146 patients were identified who developed acute coronary syndrome: 117 were classified as non–ST–elevation myocardial infarction (80.1%); 21 (14.4%) were classified as ST–elevation myocardial infarction, and 8 (5.5%) were classified as unstable angina. After coronary angiography, most events were adjudicated as demand ischemia (type 2 myocardial infarction, n = 106, 72.6%) compared to acute coronary thrombosis (type 1 myocardial infarction, n = 37, 25.3%) and stent thrombosis (type 4B, n = 3, 2.1%). Absent or only mild, nonobstructive coronary artery disease was found in 39 patients (26.7%). In 14 patients (9.6%), acute coronary syndrome was likely due to stress-induced cardiomyopathy. Aggregate 30-day and 1-yr mortality rates were 7 and 14%, respectively. Conclusions The dominant mechanism of perioperative acute coronary syndrome in our cohort was demand ischemia. A subset of patients had no evidence of obstructive coronary artery disease, but findings were consistent with stress-induced cardiomyopathy.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J.F Iglesias ◽  
D Heg ◽  
M Roffi ◽  
D Tueller ◽  
O Muller ◽  
...  

Abstract Background Newest generation drug-eluting stents (DES) combining ultrathin cobalt chromium platforms with biodegradable polymers may reduce target lesion failure (TLF) as compared to second generation DES among patients with acute coronary syndrome (ACS). While previous studies indicated a potential benefit within the first two years after percutaneous coronary intervention (PCI), it remains uncertain whether the clinical benefit persists after complete degradation of the polymer coating. Purpose To compare the long-term effects of ultrathin-strut biodegradable polymer sirolimus-eluting stents (BP-SES) versus thin-strut durable polymer everolimus-eluting stents (DP-EES) for PCI in patients with ACS. Methods We performed a subgroup analysis of ACS patients included into the BIOSCIENCE trial (NCT01443104), a randomized trial comparing BP-SES with DP-EES. The primary endpoint of the present post-hoc analysis was TLF, a composite of cardiac death, target vessel myocardial infarction (MI) and clinically indicated target lesion revascularization (TLR), at 5 years. Results Among 2,119 patients enrolled between March 2012 and May 2013, 1,131 (53%) presented with ACS (ST-segment elevation myocardial infarction, 36%). Compared to patients with stable CAD, ACS patients were younger, had a lower baseline cardiac risk profile, including a lower prevalence of hypertension, hypercholesterolaemia, diabetes mellitus, and peripheral artery disease, and had a greater incidence of previous revascularization procedures. At 5 years, TLF occurred similarly in 89 patients (cumulative incidence, 16.9%) treated with BP-SES and 85 patients (16.0%) treated with DP-EES (RR 1.04; 95% CI 0.78–1.41; p=0.78) in patients with ACS, and in 109 patients (24.1%) treated with BP-SES and 104 patients (21.8%) treated with DP-EES (RR 1.11; 95% CI 0.85–1.45; p=0.46) in stable CAD patients (p for interaction=0.77) (Figure 1, Panel A). Cumulative incidences of cardiac death (8% vs. 7%; p=0.66), target vessel MI (5.2% vs. 5.8%; p=0.66), clinically indicated TLR (8.9% vs. 8.3%; p=0.63) (Figure 1, Panel B-D), and definite thrombosis (1.4% vs. 1.0%; p=0.57) at 5 years were similar among ACS patients treated with ultrathin-strut BP-SES or thin-strut DP-EES. Overall, there was no interaction between clinical presentation and treatment effect of BP-SES versus DP-EES. Conclusion In a subgroup analysis of the BIOSCIENCE trial, we found no difference in long-term clinical outcomes between ACS patients treated with ultrathin-strut BP-SES or thin-strut DP-EES at five years. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Unrestricted research grant to the institution from Biotronik AG, Switzerland


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
D Doudesis ◽  
J Yang ◽  
A Tsanas ◽  
C Stables ◽  
A Shah ◽  
...  

Abstract Introduction The myocardial-ischemic-injury-index (MI3) is a promising machine learned algorithm that predicts the likelihood of myocardial infarction in patients with suspected acute coronary syndrome. Whether this algorithm performs well in unselected patients or predicts recurrent events is unknown. Methods In an observational analysis from a multi-centre randomised trial, we included all patients with suspected acute coronary syndrome and serial high-sensitivity cardiac troponin I measurements without ST-segment elevation myocardial infarction. Using gradient boosting, MI3 incorporates age, sex, and two troponin measurements to compute a value (0–100) reflecting an individual's likelihood of myocardial infarction, and estimates the negative predictive value (NPV) and positive predictive value (PPV). Model performance for an index diagnosis of myocardial infarction, and for subsequent myocardial infarction or cardiovascular death at one year was determined using previously defined low- and high-probability thresholds (1.6 and 49.7, respectively). Results In total 20,761 of 48,282 (43%) patients (64±16 years, 46% women) were eligible of whom 3,278 (15.8%) had myocardial infarction. MI3 was well discriminated with an area under the receiver-operating-characteristic curve of 0.949 (95% confidence interval 0.946–0.952) identifying 12,983 (62.5%) patients as low-probability (sensitivity 99.3% [99.0–99.6%], NPV 99.8% [99.8–99.9%]), and 2,961 (14.3%) as high-probability (specificity 95.0% [94.7–95.3%], PPV 70.4% [69–71.9%]). At one year, subsequent myocardial infarction or cardiovascular death occurred more often in high-probability compared to low-probability patients (17.6% [520/2,961] versus 1.5% [197/12,983], P&lt;0.001). Conclusions In unselected consecutive patients with suspected acute coronary syndrome, the MI3 algorithm accurately estimates the likelihood of myocardial infarction and predicts probability of subsequent adverse cardiovascular events. Performance of MI3 at example thresholds Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Medical Research Council


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Elharram ◽  
A Sharma ◽  
W White ◽  
G Bakris ◽  
P Rossignol ◽  
...  

Abstract Background The timing of enrolment following an acute coronary syndrome (ACS) may influence cardiovascular (CV) outcomes and potentially treatment effect in clinical trials. Using a large contemporary trial in patients with type 2 diabetes mellitus (T2DM) post-ACS, we examined the impact of timing of enrolment on subsequent CV outcomes. Methods EXAMINE was a randomized trial of alogliptin versus placebo in 5380 patients with T2DM and a recent ACS. The primary outcome was a composite of CV death, non-fatal myocardial infarction [MI], or non-fatal stroke. The median follow-up was 18 months. In this post hoc analysis, we examined the occurrence of subsequent CV events by timing of enrollment divided by tertiles of time from ACS to randomization: 8–34, 35–56, and 57–141 days. Results Patients randomized early (compared to the latest times) had less comorbidities at baseline including a history of heart failure (HF; 24.7% vs. 33.0%), prior coronary artery bypass graft (9.6% vs. 15.9%), or atrial fibrillation (5.9% vs. 9.4%). Despite the reduced comorbidity burden, the risk of the primary outcome was highest in patients randomized early compared to the latest time (adjusted hazard ratio [aHR] 1.47; 95% CI 1.21–1.74) (Figure 1). Similarly, patients randomized early had an increased risk of recurrent MI (aHR 1.51; 95% CI 1.17–1.96) and HF hospitalization (1.49; 95% CI 1.05–2.10). Conclusion In a contemporary cohort of T2DM with a recent ACS, early randomization following the ACS increases the risk of CV events including recurrent MI and HF hospitalization. This should be taken into account when designing future clinical trials. Figure 1 Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Takeda Pharmaceutical


BMJ Open ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. e045650
Author(s):  
Sidse Kjærhus Nørgaard ◽  
Elisabeth Reinhardt Mathiesen ◽  
Kirsten Nørgaard ◽  
Tine Dalsgaard Clausen ◽  
Peter Damm ◽  
...  

IntroductionFaster-acting insulin aspart (Fiasp) is approved for use in pregnancy and lactation, but no clinical study has evaluated its effects during this life stage in women with pre-existing diabetes. The aim of the CopenFast trial is to evaluate the effect of Fiasp compared with insulin aspart (NovoRapid) on maternal glycaemic control during pregnancy, delivery and lactation and on fetal growth and infant health.Methods and analysisAn open-label randomised controlled trial of pregnant women with type 1 or type 2 diabetes including women on multiple daily injection (MDI) therapy or insulin pump therapy. During a 2-year inclusion period, approximately 220 women will be randomised 1:1 to Fiasp or NovoRapid in early pregnancy and followed until 3 months after delivery. At 9, 21 and 33 gestational weeks and during planned induction of labour or caesarean section, women are offered blinded continuous glucose monitoring (CGM) for 7 days. Randomisation will stratify for type of diabetes and insulin treatment modality (MDI or insulin pump therapy, respectively). Health status of the infants will be followed until 3 months of age. The primary outcome is birth weight SD score adjusted for gestational age and gender. Secondary outcomes include maternal glycaemic control including glycated haemoglobin, preprandial and postprandial self-monitored plasma glucose levels, episodes of mild and severe hypoglycaemia, maternal gestational weight gain and weight retention, CGM time spent in, above and below target ranges as well as pregnancy outcomes including pre-eclampsia, preterm delivery, perinatal mortality and neonatal morbidity. Data analysis will be performed according to the intention-to-treat principle.Ethics and disseminationThe trial has been approved by the Regional Ethics Committee (H-19029966) on 7 August 2019. Results will be sought disseminated in peer-reviewed journals and at scientific meetings.Trial registration numberNCT03770767


2019 ◽  
Vol 72 (1) ◽  
pp. 137-141
Author(s):  
Olga Wajtryt ◽  
Tadeusz M Zielonka ◽  
Aleksandra Kaszyńska ◽  
Andrzej Falkowski ◽  
Katarzyna Życińska

Kounis syndrome or allergic myocardial infarction is an acute coronary syndrome in the course of an allergic reaction. In allergic patients in response to a specific condition - nourishment, inhalation, environmental substances, drug or insect bite there is an allergic reaction involving many different cells and mediators that can cause coronary artery spasm or initiate the process of rupture and activation of atherosclerotic plaque resulting in acute coronary syndrome. The paper describes a case of a young man with allergy to pollen and confirmed sensitization to nuts, who developed a full-blown anaphylactic shock after eating the nut mix and experienced a rapidly passing acute coronary syndrome with troponin up to 4.7 μg/L. An increased concentration of tryptase (15 μg/L), total IgE (> 3,000 IU/mL) and specific anti-nut IgE (55.1 kUA/L) were found. Based on the course of the disease and the results of allergic and cardiac tests, allergic type 1 myocardial infarction, i.e. caused by coronary artery spasm, was diagnosed. During the hospitalization, the patient’s condition improved quickly and after a few days he left the hospital without the signs of permanent damage to the heart muscle.


Heart Asia ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. e011142 ◽  
Author(s):  
Rugheed Ghadban ◽  
Tariq Enezate ◽  
Joshua Payne ◽  
Haytham Allaham ◽  
Ahmad Halawa ◽  
...  

BackgroundMorphine is widely used for pain control in patients with acute coronary syndrome (ACS). Several studies have questioned the safety of morphine in this setting with a concern of interaction with and reduced efficacy of antiplatelet agents.ObjectiveThis study aims to systematically review the safety of morphine use in ACS.MethodsMEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were queried from inception through April 2018. Studies comparing morphine to nonmorphine use in ACS were included. Study endpoints included: in-hospital myocardial infarction (MI), all-cause mortality, stroke, major bleeding, minor bleeding and dyspnoea.ResultsA total of 64 323 patients with ACS were included from eight studies, seven of which were observational studies and one was a randomised controlled trial. The use of morphine was associated with increased risk of in-hospital recurrent MI (OR 1.30, 95% CI 1.18 to 1.43, p < 0.00001). There was, however, no significant difference in terms of all-cause mortality (OR 0.87, 95% CI 0.62 to 1.22, p = 0.44), stroke (OR 0.81, 95% CI 0.39 to 1.66, p = 0.57), major bleeding (OR 0.49, 95% CI 0.24 to 1.00, p = 0.05), minor bleeding (OR 0.98, 95% CI 0.41 to 2.34, p = 0.97), or dyspnoea (OR 0.55, 95% CI 0.16 to 1.83, p = 0.33).ConclusionThe use of morphine for pain control in ACS was associated with an increased risk of in-hospital recurrent MI. Randomised clinical trials are needed to further investigate the safety of morphine in ACS.


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