Infarct severity and outcomes in ST-elevation myocardial infarction patients without standard modifiable risk factors - A multicenter cardiac magnetic resonance study.

BACKGROUND: Standard modifiable cardiovascular risk factors (SMuRFs) are well-established players in the pathogenesis of ST-elevation myocardial infarction (STEMI). However, in a significant proportion of STEMI patients, no SMuRFs can be identified, and the outcomes of this subgroup are not well described. OBJECTIVES: To assess the infarct characteristics at myocardial-tissue level and subsequent clinical outcomes in SMuRF-less STEMIs. METHODS: This multicenter, individual patient-data analysis included 2012 STEMI patients enrolled in four cardiac magnetic resonance (CMR) imaging studies conducted in Austria, Germany, Scotland, and the Netherlands. Unstable patients at time of CMR (e.g. cardiogenic shock/after cardiac arrest) were excluded. SMuRF-less was defined as absence of hypertension, smoking, hypercholesterolemia, and diabetes mellitus. All patients underwent CMR 3(interquartile range [IQR]:2-4) days after infarction to assess left ventricular (LV) volumes and ejection fraction, infarct size and microvascular obstruction (MVO). Clinical endpoints were defined as major adverse cardiovascular events (MACE), including all-cause mortality, re-infarction and heart failure. RESULTS: No SMuRF was identified in 185 patients (9%). These SMuRF-less patients were older, more often male, had lower TIMI risk score and pre-interventional TIMI flow, and less frequently multivessel-disease. SMuRF-less patients did not show significant differences in CMR markers compared to patients with SMuRFs (all p > 0.10). During a median follow-up of 12 (IQR:12-27) months, 199 patients (10%) experienced a MACE. No significant difference in MACE rates was observed between SMuRF-less patients and patients with SMuRFs (8vs.10%, p = 0.39). CONCLUSIONS: In this large individual patient-data pooled analysis of low-risk STEMI patients, infarct characteristics and clinical outcomes were not different according to SMuRF status.

Coronary perforation incidence, outcomes and temporal trends (COPIT): a systematic review and meta-analysis.

Coronary perforation is a potentially life-threatening complication of percutaneous coronary intervention (PCI). We studied incidence, outcomes and temporal trends following PCI-related coronary artery perforation (CAP). METHODS: Prospective systematic review and meta-analysis including meta-regression using MEDLINE and EMBASE to November 2020. We included 'all-comer' PCI cohorts including large PCI registries and randomised controlled trials and excluding registries or trials limited to PCI in high-risk populations such as chronic total occlusion PCI or cohorts treated only with atheroablative devices. Regression analysis and corresponding correlation coefficients were performed comparing perforation incidence, mortality rate, tamponade rate and the rate of Ellis III perforations against the midpoint (year) of data collection to determine if a significant temporal relationship was present. RESULTS: 3997 studies were screened for inclusion. 67 studies met eligibility criteria with a total of 5 568 191 PCIs included over a 38-year period (1982-2020). The overall pooled incidence of perforation was 0.39% (95% CI 0.34% to 0.45%) and remained similar throughout the study period. Around 1 in 5 coronary perforations led to tamponade (21.1%). Ellis III perforations are increasing in frequency and account for 43% of all perforations. Perforation mortality has trended lower over the years (7.5%; 95% CI 6.7% to 8.4%). Perforation risk factors derived using meta-regression were female sex, hypertension, chronic kidney disease and previous coronary bypass grafting. Coronary perforation was most frequently caused by distal wire exit (37%) followed by balloon dilation catheters (28%). Covered stents were used to treat 25% of perforations, with emergency cardiac surgery needed in 17%. CONCLUSION: Coronary perforation complicates approximately 1 in 250 PCIs. Ellis III perforations are increasing in incidence although it is unclear whether this is due to reporting bias. Despite this, the overall perforation mortality rate (7.5%) has trended lower in recent years. Limitations of our findings include bias that may be introduced through analysis of multidesign studies and registries without pre-specified standardised perforation reporting CMore research into coronary perforation management including the optimal use of covered stents seems warranted. PROSPERO REGISTRATION NUMBER: CRD42020207881.

Current Smoking and Prognosis After Acute ST-Segment Elevation Myocardial Infarction: New Pathophysiological Insights.

OBJECTIVES: The aim of this study was to mechanistically investigate associations among cigarette smoking, microvascular pathology, and longer term health outcomes in patients with acute ST-segment elevation myocardial infarction (MI). BACKGROUND: The pathophysiology of myocardial reperfusion injury and prognosis in smokers with acute ST-segment elevation MI is incompletely understood. METHODS: Patients were prospectively enrolled during emergency percutaneous coronary intervention. Microvascular function in the culprit artery was measured invasively. Contrast-enhanced magnetic resonance imaging (1.5-T) was performed 2 days and 6 months post-MI. Infarct size and microvascular obstruction were assessed using late gadolinium enhancement imaging. Myocardial hemorrhage was assessed with T2* mapping. Pre-specified endpoints included: 1) all-cause death or first heart failure hospitalization; and 2) cardiac death, nonfatal MI, or urgent coronary revascularization (major adverse cardiovascular events). Binary logistic regression (odds ratio [OR] with 95% confidence interval [CI]) with smoking status was used. RESULTS: In total, 324 patients with ST-segment elevation MI were enrolled (mean age 59 years, 73% men, 60% current smokers). Current smokers were younger (age 55 ± 11 years vs. 65 ± 10 years, p < 0.001), with fewer patients with hypertension (52 ± 27% vs. 53 ± 41%, p = 0.007). Smokers had better TIMI (Thrombolysis In Myocardial Infarction) flow grade (≥2 vs. ≤1, p = 0.024) and ST-segment resolution (none vs. partial vs. complete, p = 0.010) post-percutaneous coronary intervention. On day 1, smokers had higher circulating C-reactive protein, neutrophil, and monocyte levels. Two days post-MI, smoking independently predicted infarct zone hemorrhage (OR: 2.76; 95% CI: 1.42 to 5.37; p = 0.003). After a median follow-up period of 4 years, smoking independently predicted all-cause death or heart failure events (OR: 2.20; 95% CI: 1.07 to 4.54) and major adverse cardiovascular events (OR: 2.79; 95% CI: 2.30 to 5.99). CONCLUSIONS: Smoking is associated with enhanced inflammation acutely, infarct-zone hemorrhage subsequently, and longer term adverse cardiac outcomes. Inflammation and irreversible myocardial hemorrhage post-MI represent mechanistic drivers for adverse long-term prognosis in smokers. (Detection and Significance of Heart Injury in ST Elevation Myocardial Infarction. [BHF MR-MI]; NCT02072850).

Hypertension, Microvascular Pathology, and Prognosis After an Acute Myocardial Infarction.

The rationale for our study was to investigate the pathophysiology of microvascular injury in patients with acute ST-segment-elevation myocardial infarction in relation to a history of hypertension. We undertook a cohort study using invasive and noninvasive measures of microvascular injury, cardiac magnetic resonance imaging at 2 days and 6 months, and assessed health outcomes in the longer term. Three hundred twenty-four patients with acute myocardial infarction (mean age, 59 [12] years; blood pressure, 135 [25] / 79 [14] mm Hg; 237 [73%] male, 105 [32%] with antecedent hypertension) were prospectively enrolled during emergency percutaneous coronary intervention. Compared with patients without antecedent hypertension, patients with hypertension were older (63 [12] years versus 57 [11] years; P<0.001) and a lower proportion were cigarette smokers (52 [50%] versus 144 [66%]; P=0.007). Coronary blood flow, microvascular resistance within the culprit artery, infarct pathologies, inflammation (C-reactive protein and interleukin-6) were not associated with hypertension. Compared with patients without antecedent hypertension, patients with hypertension had less improvement in left ventricular ejection fraction at 6 months from baseline (5.3 [8.2]% versus 7.4 [7.6]%; P=0.040). Antecedent hypertension was a multivariable associate of incident myocardial hemorrhage 2-day post-MI (1.81 [0.98-3.34]; P=0.059) and all-cause death or heart failure (n=47 events, n=24 with hypertension; 2.53 [1.28-4.98]; P=0.007) postdischarge (median follow-up 4 years). Severe progressive microvascular injury is implicated in the pathophysiology and prognosis of patients with a history of hypertension and acute myocardial infarction. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT02072850.

Persistent Iron Within the Infarct Core After ST-Segment Elevation Myocardial Infarction: Implications for Left Ventricular Remodeling and Health Outcomes.

OBJECTIVES: This study sought to determine the incidence and prognostic significance of persistent iron in patients post-ST-segment elevation myocardial infarction (STEMI). BACKGROUND: The clinical significance of persistent iron within the infarct core after STEMI complicated by acute myocardial hemorrhage is poorly understood. METHODS: Patients who sustained an acute STEMI were enrolled in a cohort study (BHF MR-MI [Detection and Significance of Heart Injury in ST Elevation Myocardial Infarction]). Cardiac magnetic resonance imaging including T2* (observed time constant for the decay of transverse magnetization seen with gradient-echo sequences) mapping was performed at 2 days and 6 months post-STEMI. Myocardial hemorrhage or iron was defined as a hypointense infarct core with T2* signal <20 ms. RESULTS: A total of 203 patients (age 57 ± 11 years, n = 158 [78%] male) had evaluable T2* maps at 2 days and 6 months post-STEMI; 74 (36%) patients had myocardial hemorrhage at baseline, and 44 (59%) of these patients had persistent iron at 6 months. Clinical associates of persistent iron included heart rate (p = 0.009), the absence of a history of hypertension (p = 0.017), and infarct size (p = 0.028). The presence of persistent iron was associated with worsening left ventricular (LV) end-diastolic volume (regression coefficient: 21.10; 95% confidence interval [CI]: 10.92 to 31.27; p < 0.001) and worsening LV ejection fraction (regression coefficient: -6.47; 95% CI: -9.22 to -3.72; p < 0.001). Persistent iron was associated with the subsequent occurrence of all-cause death or heart failure (hazard ratio: 3.91; 95% CI: 1.37 to 11.14; p = 0.011) and major adverse cardiac events (hazard ratio: 3.24; 95% CI: 1.09 to 9.64; p = 0.035) (median follow-up duration 1,457 days [range 233 to 1,734 days]). CONCLUSIONS: Persistent iron at 6 months post-STEMI is associated with worse LV and longer-term health outcomes. (Detection and Significance of Heart Injury in ST Elevation Myocardial Infarction [BHF MR-MI]; NCT02072850).

Safety of guidewire-based measurement of fractional flow reserve and the index of microvascular resistance using intravenous adenosine in patients with acute or recent myocardial infarction.

AIMS: Coronary guidewire-based diagnostic assessments with hyperemia may cause iatrogenic complications. We assessed the safety of guidewire-based measurement of coronary physiology, using intravenous adenosine, in patients with an acute coronary syndrome. METHODS: We prospectively enrolled invasively managed STEMI and NSTEMI patients in two simultaneously conducted studies in 6 centers (NCT01764334; NCT02072850). All of the participants underwent a diagnostic coronary guidewire study using intravenous adenosine (140 µg/kg/min) infusion for 1-2 min. The patients were prospectively assessed for the occurrence of serious adverse events (SAEs) and symptoms and invasively measured hemodynamics were also recorded. RESULTS: 648 patients (n=298 STEMI patients in 1 hospital; mean time to reperfusion 253 min; n=350 NSTEMI in 6 hospitals; median time to angiography from index chest pain episode 3 (2, 5) days) were included between March 2011 and May 2013. Two NSTEMI patients (0.3% overall) experienced a coronary dissection related to the guidewire. No guidewire dissections occurred in the STEMI patients. Chest symptoms were reported in the majority (86%) of patient's symptoms during the adenosine infusion. No serious adverse events occurred during infusion of adenosine and all of the symptoms resolved after the infusion ceased. CONCLUSIONS: In this multicenter analysis, guidewire-based measurement of FFR and IMR using intravenous adenosine was safe in patients following STEMI or NSTEMI. Self-limiting symptoms were common but not associated with serious adverse events. Finally, coronary dissection in STEMI and NSTEMI patients was noted to be a rare phenomenon.

Adenosine: physiology, pharmacology, and clinical applications.

Adenosine is a ubiquitous extracellular signaling molecule with essential functions in human physiology. Due to the widespread expression of adenosine receptors, it has far-reaching effects across many different organ systems. With a prominent role in the cardiovascular system, it has been extensively studied for both its therapeutic and diagnostic abilities. One of the key areas of use is in the coronary circulation whereby adenosine produces a hyperemic response. An important target of adenosine is the coronary microcirculation whereby adenosine acts as a prominent vasodilator with many of the beneficial effects of adenosine reflected in its capacity to affect the microvessels. Adenosine also has an important role in the pre-conditioned state and also in the attenuation of ischemia-reperfusion injury. This review examines the physiology, pharmacology, and therapeutic applications of adenosine in the human cardiovascular system and provides a brief overview of important aspects of the adenosine-cardiac interaction. It also examines the role of adenosine in the coronary hyperemic response and discusses the use of adenosine for this purpose. After recent concerns about the use of adenosine, a discussion regarding safety of this drug is provided. A brief review of novel agents used to initiate coronary hyperemia is also provided.