Intracoronary thrombolysis in ST-elevation myocardial infarction: a systematic review and meta-analysis.

BACKGROUND: Despite restoration of epicardial blood flow in acute ST-elevation myocardial infarction (STEMI), inadequate microcirculatory perfusion is common and portends a poor prognosis. Intracoronary (IC) thrombolytic therapy can reduce microvascular thrombotic burden; however, contemporary studies have produced conflicting outcomes. OBJECTIVES: This meta-analysis aims to evaluate the efficacy and safety of adjunctive IC thrombolytic therapy at the time of primary percutaneous coronary intervention (PCI) among patients with STEMI. METHODS: Comprehensive literature search of six electronic databases identified relevant randomised controlled trials. The primary outcome was major adverse cardiac events (MACE). The pooled risk ratio (RR) and weighted mean difference (WMD) with a 95% CI were calculated. RESULTS: 12 studies with 1915 patients were included. IC thrombolysis was associated with a significantly lower incidence of MACE (RR=0.65, 95% CI 0.51 to 0.82, I2=0%, p<0.0004) and improved left ventricular ejection fraction (WMD=1.87; 95% CI 1.07 to 2.67; I2=25%; p<0.0001). Subgroup analysis demonstrated a significant reduction in MACE for trials using non-fibrin (RR=0.39, 95% CI 0.20 to 0.78, I2=0%, p=0.007) and moderately fibrin-specific thrombolytic agents (RR=0.62, 95% CI 0.47 to 0.83, I2=0%, p=0.001). No significant reduction was observed in studies using highly fibrin-specific thrombolytic agents (RR=1.10, 95% CI 0.62 to 1.96, I2=0%, p=0.75). Furthermore, there were no significant differences in mortality (RR=0.91; 95% CI 0.48 to 1.71; I2=0%; p=0.77) or bleeding events (major bleeding, RR=1.24; 95% CI 0.47 to 3.28; I2=0%; p=0.67; minor bleeding, RR=1.47; 95% CI 0.90 to 2.40; I2=0%; p=0.12). CONCLUSION: Adjunctive IC thrombolysis at the time of primary PCI in patients with STEMI improves clinical and myocardial perfusion parameters without an increased rate of bleeding. Further research is needed to optimise the selection of thrombolytic agents and treatment protocols.

Prevalence of Coronary Vasomotor Disorders in Patients With Angina and Nonobstructive Coronary Arteries: A Sydney Experience.

BACKGROUND: Patients with angina and non-obstructive coronary arteries (ANOCA) frequently have coronary vasomotor disorders (CVaD), characterised by transient pathological vasoconstriction and/or impaired microvascular vasodilatation. Functional coronary angiography is the gold standard for diagnosing CVaD. Despite recommendations, testing is only available at a limited number of Australian and New Zealand centres. This study aimed to determine the prevalence of CVaDs in an Australian ANOCA population and identify predictive factors associated with specific endotypes. METHOD: Functional coronary angiography was performed in patients with suspected ANOCA. Vasoreactivity testing was performed using intracoronary acetylcholine provocation. A pressure-temperature sensor guidewire was used for coronary physiology assessment. Comprehensive clinical data on patient characteristics, cardiac risk factors, and symptom profiles was collected before testing. RESULTS: This prospective observational study at Royal Prince Alfred and Concord Repatriation General Hospital included 110 patients (58±13 years with 63.6% women), with 81.8% (90/110) having a CVaD. Regarding specific ANOCA endotypes, microvascular angina (MVA) occurred in 31.8% (35/110) of cases, vasospastic angina (VSA) in 25.5% (28/110) and a mixed presentation of MVA and VSA in 24.5% (27/110) of patients. Patients with CVaD were found to be older (59±11 vs 51±15, p=0.024), overweight (61.1% vs 15.0%, p<0.001) and had a worse quality of life (EuroQol 5 Dimensions-5 Levels; 0.61 vs 0.67, p=0.043). MVA was associated with being overweight (odds ratio [OR] 4.2 [95% confidence interval [CI] 1.9-9.3]; p=0.015) and ischaemia on stress testing (OR 2.4 [95% CI 1.1-4.3]; p=0.028), while VSA was associated with smoking (OR 9.1 [95% CI 2.21-39.3]; p=0.007). CONCLUSIONS: Coronary vasomotor disorders are highly prevalent among ANOCA patients. This study highlights the importance of increasing national awareness and the use of functional coronary angiography to evaluate and manage this unique cohort.

Multivessel Coronary Function Testing Increases Diagnostic Yield in Patients With Angina and Nonobstructive Coronary Arteries.

BACKGROUND: Invasive CFT is the gold standard for diagnosing coronary vasomotor dysfunction in patients with ANOCA. Most institutions recommend only testing the left coronary circulation. Therefore, it is unknown whether testing multiple coronary territories would increase diagnostic yield. OBJECTIVES: The aim of this study was to evaluate the diagnostic yield of multivessel, compared with single-vessel, invasive coronary function testing (CFT) in patients with angina and nonobstructive coronary arteries (ANOCA). METHODS: Multivessel CFT was systematically performed in patients with suspected ANOCA. Vasoreactivity testing was performed using acetylcholine provocation in the left (20 to 200 µg) and right (20 to 80µg) coronary arteries. A pressure-temperature sensor guidewire was used for coronary physiology assessment in all three epicardial vessels. RESULTS: This multicenter study included a total of 228 vessels from 80 patients (57.8 ± 11.8 years of age, 60% women). Compared with single-vessel CFT, multivessel testing resulted in more patients diagnosed with coronary vasomotor dysfunction (86.3% vs 68.8%; P = 0.0005), coronary artery spasm (60.0% vs 47.5%; P = 0.004), and CMD (62.5% vs 36.3%; P < 0.001). Coronary artery spasm (n = 48) predominated in the left coronary system (n = 38), though isolated right coronary spasm was noted in 20.8% (n = 10). Coronary microvascular dysfunction (CMD), defined by abnormal index of microcirculatory resistance and/or coronary flow reserve, was present 62.5% of the cohort (n = 50). Among the cohort with CMD, 27 patients (33.8%) had 1-vessel CMD, 15 patients (18.8%) had 2-vessel CMD, and 8 patients (10%) had 3-vessel CMD. CMD was observed at a similar rate in the territories supplied by all 3 major coronary vessels (left anterior descending coronary artery = 36.3%, left circumflex coronary artery = 33.8%, right coronary artery = 31.3%; P = 0.486). CONCLUSIONS: Multivessel CFT resulted in an increased diagnostic yield in patients with ANOCA compared with single-vessel testing. The results of this study suggest that multivessel CFT has a role in the management of patients with ANOCA.

A case report of successful primary percutaneous coronary intervention to an occluded anomalous left main coronary artery arising from the right coronary sinus.

Background: Anomalous aortic origin of a coronary artery from the opposite sinus is a rare congenital abnormality that may be encountered during primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). Case summary: A 65-year-old man presented with chest pain and signs of heart failure. Electrocardiogram demonstrated atrial fibrillation with ST elevation in the high lateral leads, and he was taken emergently to the cardiac catheterization laboratory for primary PCI. Coronary angiography identified the culprit to be an occluded anomalous left main coronary artery (LMCA) arising from the right coronary cusp, and primary PCI was successfully performed in the LMCA and the left anterior descending artery (LAD). Computed tomography angiography confirmed a benign retroaortic course of the anomalous LMCA with no additional high-risk features, as well as a new left atrial appendage thrombus. He subsequently developed deep venous thrombosis, acute pulmonary embolism, and acute kidney injury secondary to renal artery embolism with associated infarction. Workup for patent foramen ovale and thrombophilia were negative, and he was discharged in a stable condition. At 2-month follow-up, he was asymptomatic with no evidence of myocardial ischaemia on stress cardiac magnetic resonance imaging. Discussion: We present the first reported case of an occluded anomalous LMCA arising from the right coronary sinus in a patient presenting with STEMI. Rapid recognition of this congenital anomaly and selection of an appropriate guide catheter were keys to achieving timely reperfusion and a good outcome in this case.

Role of Cardiac Magnetic Resonance Imaging and Troponin T in Definitive Diagnosis of Myocardial Infarction With Nonobstructive Coronary Arteries (MINOCA).

BACKGROUND: It is unknown whether the degree of high-sensitivity troponin T (hsTropT) elevation in patients with suspected myocardial infarction without obstructive coronary arteries (MINOCA) presentations can help predict the likelihood of an abnormal cardiac magnetic resonance (CMR) scan. In this study we describe the diagnostic utility of CMR in patients with MINOCA and assesses the effect of peak hsTropT levels at presentation on CMR diagnostic yield. METHODS: Records of consecutive patients (n = 1407) referred for CMR at a tertiary referral hospital between January 2016 and September 2021 were reviewed. A total of 70 patients met the criteria of MINOCA including ischemic chest pain, elevated peak hsTropT, and nonobstructive coronary artery disease (< 50% stenosis). The peak hsTropT levels within 72 hours of admission were identified. CMR images were generated using a 3.0 T Siemens scanner. Predictors of having an abnormal CMR were evaluated. RESULTS: CMR established a diagnosis in 71% (n = 50) of patients, with the most common CMR diagnosis being myopericarditis (n = 27; 39%). Time to CMR was an independent predictor of a normal CMR scan (odds ratio, 0.98; 95% confidence interval, 0.97-0.999). Peak hsTropT had a high diagnostic accuracy for identifying patients with an abnormal CMR scan (area under the receiver operator characteristic curve, 0.81; P < 0.001). The optimal hsTropT cutoff was 166 ng/L, with 72% sensitivity and specificity. A troponin value ≥ 166 ng/L was independently predictive of an abnormal CMR scan (odds ratio, 4.76; 95% confidence interval, 1.32-17.11). CONCLUSIONS: HsTropT and early CMR imaging are independently predictive of an abnormal CMR scan in patients with MINOCA. Additionally, the use of a hsTropT cutoff provides incremental predictive value to clinical parameters and time to CMR scanning in determining an abnormal scan.

A unique case report of relapsing eosinophilic myocarditis causing atrial myopathy and persistent sinus arrest.

BACKGROUND: Eosinophilic myocarditis (EM) is a rare and devastating condition. The underlying cause of EM is unknown, and the natural history is not well understood. CASE SUMMARY: A 20-year-old male presented in cardiogenic shock with preceding 24-h history of pleuritic chest pain associated with nausea and vomiting. Electrocardiogram showed sinus tachycardia with widespread ST elevation, significantly raised high-sensitivity troponin T, and raised white cell count with eosinophilia. Transthoracic echocardiogram demonstrated severe left ventricular (LV) impairment and a moderate-sized pericardial effusion. Right ventricular (RV) endomyocardial biopsy and bone marrow biopsy were performed, with both demonstrating prominent eosinophilia. He was initiated on pulse methylprednisolone leading to rapid clinical improvement with normalization of LV function. Day 9 after discharge, he was readmitted to hospital with presyncope and right heart failure. Electrocardiogram revealed junctional escape rhythm, and cardiac magnetic resonance imaging showed scarring confined to the atria. The patient was treated with mepolizumab and underwent an electrophysiology study with electroanatomical mapping, demonstrating sinus arrest and the absence of electrical activity throughout the right atrium. After much deliberation, an implantable cardioverter-defibrillator was implanted with a deep septal RV pacing lead and an apical RV defibrillator lead. DISCUSSION: We present a unique case of EM with two distinct phases: the first marked by severe LV impairment resolving with immunosuppression; the second characterized by atrial cardiomyopathy leading to persistent symptomatic sinus arrest necessitating permanent pacing. Close follow-up of EM after initial remission is essential to monitor for further complications including heart failure and arrhythmias.

Fractional Flow Reserve and Instantaneous Wave-Free Ratio Predict Pathological Wall Shear Stress in Coronary Arteries: Implications for Understanding the Pathophysiological Impact of Functionally Significant Coronary Stenoses.

Background The pathophysiological mechanism behind adverse outcomes associated with ischemia-inducing epicardial coronary stenoses and microcirculatory dysfunction remains unclear. Wall shear stress (WSS) plays an important role in atherosclerotic plaque progression and vulnerability. We aimed to evaluate the relationship between WSS, functionally significant epicardial coronary stenoses, and microcirculatory dysfunction. Methods and Results Patients undergoing invasive coronary physiology testing were included. Fractional flow reserve, instantaneous wave-free ratio, and the index of microcirculatory resistance were measured. Quantitative coronary angiography was used to obtain the lesion percentage diameter stenosis. Computational fluid dynamics analysis was performed to calculate WSS parameters. Multiple regression analysis was performed to calculate the standardized regression coefficient (ß) for the coronary physiology indices. A total of 107 vessels from 88 patients were included. Fractional flow reserve independently predicted the total area of low WSS (ß=-0.44; 95% CI, -0.62 to -0.25; P<0.001) and maximum lesion WSS (ß=-0.53; 95% CI, -0.70 to -0.36; P<0.001) after adjusting for percentage diameter stenosis and index of microcirculatory resistance. Similarly, instantaneous wave-free ratio also independently predicted the total area of low WSS (ß=-0.45; 95% CI, -0.62 to -0.28; P<0.001) and maximum lesion WSS (ß=-0.58; 95% CI, -0.73 to -0.43; P<0.001). The index of microcirculatory resistance did not predict either low or high WSS. Conclusions Fractional flow reserve and instantaneous wave-free ratio independently predicted the total burden of low WSS and maximum lesion WSS in coronary arteries. No relationship was found between microcirculatory dysfunction and WSS.

A real-world comparison of outcomes between fractional flow reserve-guided versus angiography-guided percutaneous coronary intervention.

BACKGROUND: Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) has been shown to be superior to angiography-guided PCI in randomized controlled studies. However, real-world data on the use and outcomes of FFR-guided PCI remain limited. Thus, we investigated the outcomes of patients undergoing FFR-guided PCI compared to angiography-guided PCI in a large, state-wide unselected cohort. METHODS AND RESULTS: All patients undergoing PCI between June 2017 and June 2018 in New South Wales, Australia, were included. The cohort was stratified into the FFR-guided group when concomitant FFR was performed, and the angiography-guided group when no FFR was performed. The primary outcome was a combined endpoint of death or myocardial infarction (MI). Secondary outcomes included all-cause death, cardiovascular (CVS) death, and MI. The cohort comprised 10,304 patients, of which 542 (5%) underwent FFR-guided PCI. During a mean follow-up of 12±4 months, the FFR-guided PCI group had reduced occurrence of the primary outcome (hazard ratio [HR] 0.34, 95% confidence intervals [CI] 0.20-0.56, P<0.001), all-cause death (HR 0.18, 95% CI 0.07-0.47, P = 0.001), CVS death (HR 0.21, 95% CI 0.07-0.66, P = 0.01), and MI (HR 0.46, 95% CI 0.25-0.84, P = 0.01) compared to the angiography-guided PCI group. Multivariable Cox regression analysis showed FFR-guidance to be an independent predictor of the primary outcome (HR 0.45, 95% CI 0.27-0.75, P = 0.002), all-cause death (HR 0.22, 95% CI 0.08-0.59, P = 0.003), and CVS death (HR 0.27, 95% CI 0.09-0.83, P = 0.02). CONCLUSIONS: In this real-world study of patients undergoing PCI, FFR-guidance was associated with lower rates of the primary outcome of death or MI, as well as the secondary outcomes of all-cause death and CVS death.

Abnormal shear stress and residence time are associated with proximal coronary atheroma in the presence of myocardial bridging.

BACKGROUND: Atheromatous plaques tend to form in the coronary segments proximal to a myocardial bridge (MB), but the mechanism of this occurrence remains unclear. This study evaluates the relationship between blood flow perturbations and plaque formation in patients with an MB. METHODS AND RESULTS: A total of 92 patients with an MB in the mid left anterior descending artery (LAD) and 20 patients without an MB were included. Coronary angiography, intravascular ultrasound, and coronary physiology measurements were performed. A moving-boundary computational fluid dynamics algorithm was used to derive wall shear stress (WSS) and peak residence time (PRT). Patients with an MB had lower WSS (0.46 ± 0.21 vs. 0.96 ± 0.33 Pa, p < 0.001) and higher maximal plaque burden (33.6 ± 15.0 vs. 14.2 ± 5.8%, p < 0.001) within the proximal LAD compared to those without. Plaque burden in the proximal LAD correlated significantly with proximal WSS (r = -0.51, p < 0.001) and PRT (r = 0.60, p < 0.001). In patients with an MB, the site of maximal plaque burden occurred 23.4 ± 13.3 mm proximal to the entrance of the MB, corresponding to the site of PRT. CONCLUSIONS: Regions of low WSS and high PRT occur in arterial segments proximal to an MB, and this is associated with the degree and location of coronary atheroma formation.

Red blood cell transfusion and outcomes in acute pulmonary embolism.

BACKGROUND AND OBJECTIVE: Blood transfusion has been associated with adverse outcomes in certain conditions. This study investigates the prevalence and outcomes of red blood cell (RBC) transfusion in patients with acute pulmonary embolism (PE). METHODS: Retrospective study of consecutive patients from 2000 to 2012 admitted to a tertiary hospital with a primary diagnosis of acute PE. Transfusion status during the hospital admission was ascertained. Mortality was tracked from a state-wide death database and analysed using multivariable modelling. RESULTS: A total of 73 patients (5% of all patients admitted with PE) received RBC transfusion during their admission. These patients were significantly older, had more co-morbidities, worse haemodynamics, higher simplified pulmonary embolism severity index scores, and lower plasma sodium and haemoglobin (Hb) levels at admission. Unadjusted mortality for the transfused group was significantly higher at 30-day (19% vs 4%, P < 0.001) and 6-month (40% vs 10%, P < 0.001) follow-up. Multivariable modelling showed RBC transfusion to be a significant independent predictor of mortality at 30-day (odds ratio 3.06, 95% CI: 1.17-8.01, P = 0.02) and 6-month (hazard ratio (HR) 1.97, 95% CI: 1.12-3.46, P = 0.02). Sensitivity analysis confirmed that transfused patients had higher mortality than non-transfused patients in the subgroup of patients with Hb <100 g/L. CONCLUSION: RBC transfusion in patients hospitalized with acute PE is rare and appears to be associated with increased risk of short- and long-term mortality, independent of Hb level on admission. This finding underscores the need for future randomized controlled studies on the impact of RBC transfusion in the management of patients admitted with acute PE. [Correction added on 4 May 2018, after first online publication: the word 'serum' was changed to 'plasma' throughout the article where appropriate.].

The prognostic impact of chest pain in 1306 patients presenting with confirmed acute pulmonary embolism.

BACKGROUND: The prognostic influence of chest pain in patients presenting with pulmonary embolism has not been well defined. We investigated whether the presence of chest pain at presentation affected the mortality of patients with acute pulmonary embolism. METHODS: Retrospective cohort study of consecutive patients admitted to a tertiary hospital with confirmed acute pulmonary embolism from 2000 to 2012, with study outcomes tracked using a state-wide death registry. RESULTS: Of the 1306 patients included in the study, 771 (59%) had chest pain at presentation. These patients were younger with fewer comorbidities, and had lower 6-month mortality compared to patients without chest pain (5% vs 15%, P<0.001). Chest pain was consistently found to be an independent predictor of 6-month mortality in three separate multivariable models (range of hazard ratios 0.52-0.60, all with P<0.05). The addition of chest pain to a multivariable model that included the simplified pulmonary embolism severity index, haemoglobin, and sodium led to a significant net reclassification improvement of 18% (P<0.001). CONCLUSIONS: Chest pain is a novel, favourable prognostic marker in patients with acute pulmonary embolism.

High mortality in patients presenting with acute pulmonary embolism and elevated INR not on anticoagulant therapy.

The prognostic significance of patients presenting with pulmonary embolism (PE) and elevated International Normalised Ratio (INR) not on anticoagulant therapy has not been described. We investigated whether these patients had higher mortality compared to patients with normal INR. A retrospective study of patients admitted to a tertiary hospital with acute PE from 2000 to 2012 was undertaken, with study outcomes tracked using a state-wide death registry. Patients were excluded if they were taking anticoagulants or had inadequate documentation of their INR and medication status. Of the 1,039 patients identified, 94 (9 %) had an elevated INR (> 1.2) in the absence of anticoagulant use. These patients had higher mortality at six months follow-up (26 % vs 6 %, p< 0.001) compared to controls (INR ≤ 1.2). An INR > 1.2 at diagnosis was an independent predictor of death at six months post-PE (hazard ratio [HR] 2.9, 95 % confidence interval [CI] 1.8-4.7, p< 0.001). The addition of INR to a multivariable model that included the simplified pulmonary embolism severity index (sPESI), chest pain, and serum sodium led to a significant net reclassification improvement estimated at 8.1 %. The final model's C statistic increased significantly by 0.04 (95 % CI 0.01-0.08, p=0.03) to 0.83 compared to sPESI alone (0.79). In summary, patients presenting with acute PE and elevated INR while not on anticoagulant therapy appear to be at high risk of death. Future validation studies in independent cohorts will clarify if this novel finding can be usefully incorporated into clinical decision making in patients with acute PE.

Iron Deficiency in Heart Failure: Looking Beyond Anaemia.

Iron is an essential micronutrient in many cellular processes. Iron deficiency, with or without anaemia, is common in patients with chronic heart failure. Observational studies have shown iron deficiency to be associated with worse clinical outcomes and mortality. The treatment of iron deficiency in chronic heart failure patients using intravenous iron alone has shown promise in several clinical trials, although further studies which include larger populations and longer follow-up times are needed.

Resolving the morphology of niobium carbonitride nano-precipitates in steel using atom probe tomography.

Atom probe is a powerful technique for studying the composition of nano-precipitates, but their morphology within the reconstructed data is distorted due to the so-called local magnification effect. A new technique has been developed to mitigate this limitation by characterizing the distribution of the surrounding matrix atoms, rather than those contained within the nano-precipitates themselves. A comprehensive chemical analysis enables further information on size and chemistry to be obtained. The method enables new insight into the morphology and chemistry of niobium carbonitride nano-precipitates within ferrite for a series of Nb-microalloyed ultra-thin cast strip steels. The results are supported by complementary high-resolution transmission electron microscopy.