Pressure-controlled intermittent coronary sinus occlusion improves the vasodilatory microvascular capacity and reduces myocardial injury in patients with STEMI.

BACKGROUND: Preliminary data suggest that pressure-controlled intermittent coronary sinus occlusion (PICSO) might reduce the infarct size (IS) in patients with anterior ST-elevation myocardial infarction (STEMI). However, the applicability of this therapy to patients with inferior STEMI and its exact mechanism of action is uncertain. METHODS AND RESULTS: Thirty-six patients (27 anterior and 9 inferior) with STEMI underwent PICSO-assisted-primary percutaneous intervention (PPCI) and were compared with matched controls who underwent standard PCI (n = 72). Median age was 63 (55-70) years and 82% were male. Coronary microvascular status was assessed using thermodilution-derived index of microcirculatory resistance (IMR) and the vasodilatory capacity was assessed using the resistive reserve ratio (RRR). IS and microvascular obstruction (MVO) were assessed using cardiovascular magnetic resonance imaging (CMR) within 48 h and 6 months of follow-up. At completion of PPCI, IMR improved significantly in PICSO-treated patients compared with controls in patients with either anterior (63.7 [49.8-74.6] vs. 35.9 [27.9-47.6], p < 0.001) or inferior STEMI (60.0 [47.6-67.1] vs. 22.7 [18.4-35.0], p < 0.001). RRR significantly improved after PICSO treatment for anterior (1.21 [1.01-1.42] vs. 1.73 [1.51-2.16], p = 0.002) or inferior STEMI (1.39 [1.05-1.90] vs. 2.87 [2.17-3.78], p = 0.001), whereas it did not change in controls compared with baseline. Patients treated with PICSO presented significantly less frequently with MVO (66.6% vs. 86.1%, p = 0.024) and smaller 6-month IS compared with controls (26% [17%-30%] vs. 30% [21%-37%], p = 0.045). CONCLUSION: PICSO therapy may improve microvascular function and vasodilatory capacity, which contributes to reducing IS in patients with STEMI undergoing PPCI.

Hyper-acute cardiovascular magnetic resonance T1 mapping predicts infarct characteristics in patients with ST elevation myocardial infarction.

BACKGROUND: Myocardial recovery after primary percutaneous coronary intervention in acute myocardial infarction is variable and the extent and severity of injury are difficult to predict. We sought to investigate the role of cardiovascular magnetic resonance T1 mapping in the determination of myocardial injury very early after treatment of ST-segment elevation myocardial infarction (STEMI). METHODS: STEMI patients underwent 3 T cardiovascular magnetic resonance (CMR), within 3 h of primary percutaneous intervention (PPCI). T1 mapping determined the extent (area-at-risk as %left ventricle, AAR) and severity (average T1 values of AAR) of acute myocardial injury, and related these to late gadolinium enhancement (LGE), and microvascular obstruction (MVO). The characteristics of myocardial injury within 3 h was compared with changes at 24-h to predict final infarct size. RESULTS: Forty patients were included in this study. Patients with average T1 values of AAR ≥1400 ms within 3 h of PPCI had larger LGE at 24-h (33% ±14 vs. 18% ±10, P = 0.003) and at 6-months (27% ±9 vs. 12% ±9; P < 0.001), higher incidence and larger extent of MVO (85% vs. 40%, P = 0.016) & [4.0 (0.5-9.5)% vs. 0 (0-3.0)%, P = 0.025]. The average T1 value was an independent predictor of acute LGE (ß 0.61, 95%CI 0.13 to 1.09; P = 0.015), extent of MVO (ß 0.22, 95%CI 0.03 to 0.41, P = 0.028) and final infarct size (ß 0.63, 95%CI 0.21 to 1.05; P = 0.005). Receiver-operating-characteristic analysis showed that T1 value of AAR obtained within 3-h, but not at 24-h, predicted large infarct size (LGE > 9.5%) with 100% positive predictive value at the optimal cut-off of 1400 ms (area-under-the-curve, AUC 0.88, P = 0.006). CONCLUSION: Hyper-acute T1 values of the AAR (within 3 h post PPCI, but not 24 h) predict a larger extent of MVO and infarct size at both 24 h and 6 months follow-up. Delayed CMR scanning for 24 h could not substitute the significant value of hyper-acute average T1 in determining infarct characteristics.

Beyond patency: Functional assessment of adequacy using internal mammary artery grafting to the left anterior descending artery.

INTRODUCTION: Arterial graft physiology influences the long-term outcome of coronary artery bypass grafting (CABG). We studied factors that can affect the overall resistance to flow using internal mammary artery grafting to the left anterior descending artery. METHODS: This was a prospective, nonrandomized observational study of 100 consecutive patients who underwent elective on-pump isolated or combined valve surgery and CABG. Coronary stenoses were assessed using conventional and quantitative coronary angiography assessment. The flow and pulsatility index (PI) of the grafts were assessed by transit-time flowmetry during cardioplegic arrest and at the end of the operation. Fractional polynomials were used to explore linearity, followed by multivariable regression analysis. RESULTS: Univariate analysis demonstrated higher flows at the end of the operation in patients who had higher flows with the cross-clamp on (P < .001), in males (P = .004), in patients with a low PI at the end of the operation (P = .04), and in patients with a larger size of the recipient artery (P = .005). Multivariable regression analysis showed that the graft flow at the end of the operation was significantly associated with the mean flow with the cross-clamp on (P < .001), sex (P = .003), and PI at the end of the operation (P = .003). Concomitant valve surgery did not influence flows. Male patients had 18 mL/min higher flow. CONCLUSIONS: The graft flow at the end of the operation can be determined by the flow with the cross-clamp on, the PI with the cross-clamp off and coronary artery. We reported differences in the graft flows between sexes, and for first the time, we introduced the concepts of "adequate flow" and "resistance-to-forward-flow" for patent coronary grafts.

Fire Simulation and Cardiovascular Health in Firefighters.

BACKGROUND: Rates of myocardial infarction in firefighters are increased during fire suppression duties, and are likely to reflect a combination of factors including extreme physical exertion and heat exposure. We assessed the effects of simulated fire suppression on measures of cardiovascular health in healthy firefighters. METHODS: In an open-label randomized crossover study, 19 healthy firefighters (age, 41±7 years; 16 males) performed a standardized training exercise in a fire simulation facility or light duties for 20 minutes. After each exposure, ex vivo thrombus formation, fibrinolysis, platelet activation, and forearm blood flow in response to intra-arterial infusions of endothelial-dependent and -independent vasodilators were measured. RESULTS: After fire simulation training, core temperature increased (1.0±0.1°C) and weight reduced (0.46±0.14 kg, P<0.001 for both). In comparison with control, exposure to fire simulation increased thrombus formation under low-shear (73±14%) and high-shear (66±14%) conditions (P<0.001 for both) and increased platelet-monocyte binding (7±10%, P=0.03). There was a dose-dependent increase in forearm blood flow with all vasodilators (P<0.001), which was attenuated by fire simulation in response to acetylcholine (P=0.01) and sodium nitroprusside (P=0.004). This was associated with a rise in fibrinolytic capacity, asymptomatic myocardial ischemia, and an increase in plasma cardiac troponin I concentrations (1.4 [0.8-2.5] versus 3.0 [1.7-6.4] ng/L, P=0.010). CONCLUSIONS: Exposure to extreme heat and physical exertion during fire suppression activates platelets, increases thrombus formation, impairs vascular function, and promotes myocardial ischemia and injury in healthy firefighters. Our findings provide pathogenic mechanisms to explain the association between fire suppression activity and acute myocardial infarction in firefighters. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01812317.

Dynamic changes in injured myocardium, very early after acute myocardial infarction, quantified using T1 mapping cardiovascular magnetic resonance.

BACKGROUND: It has recently been suggested that myocardial oedema follows a bimodal pattern early post ST-segment elevation myocardial infarction (STEMI). Yet, water content, quantified using tissue desiccation, did not return to normal values unlike oedema quantified by cardiovascular magnetic resonance (CMR) imaging. We studied the temporal changes in the extent and intensity of injured myocardium using T1-mapping technique within the first week after STEMI. METHODS: A first group (n = 31) underwent 3 acute 3 T CMR scans (time-point (TP) < 3 h, 24 h and 6 days), including cine, native shortened modified look-locker inversion recovery T1 mapping, T2* mapping and late gadolinium enhancement (LGE). A second group (n = 17) had a single scan at 24 h with an additional T2-weighted sequence to assess the difference in the extent of area-at-risk (AAR) compared to T1-mapping. RESULTS: The mean T1 relaxation time value within the AAR of the first group was reduced after 24 h (P < 0.001 for TP1 vs.TP2) and subsequently increased at 6 days (P = 0.041 for TP2 vs.TP3). However, the extent of AAR quantified using T1-mapping did not follow the same course, and no change was detected between TP1&TP2 (P = 1.0) but was between TP2 &TP3 (P = 0.019). In the second group, the extent of AAR was significantly larger on T1-mapping compared to T2-weighted (42 ± 15% vs. 39 ± 15%, P = 0.025). No change in LGE was detected while microvascular obstruction and intra-myocardial haemorrhage peaked at different time points within the first week of reperfusion. CONCLUSION: The intensity of oedema post-STEMI followed a bimodal pattern; while the extent of AAR did not track the same course. This discrepancy has implications for use of CMR in this context and may explain the previously reported disagreement between oedema quantified by imaging and tissue desiccation.

High-sensitivity troponin I concentrations are a marker of an advanced hypertrophic response and adverse outcomes in patients with aortic stenosis.

AIMS: High-sensitivity cardiac troponin I (cTnI) assays hold promise in detecting the transition from hypertrophy to heart failure in aortic stenosis. We sought to investigate the mechanism for troponin release in patients with aortic stenosis and whether plasma cTnI concentrations are associated with long-term outcome. METHODS AND RESULTS: Plasma cTnI concentrations were measured in two patient cohorts using a high-sensitivity assay. First, in the Mechanism Cohort, 122 patients with aortic stenosis (median age 71, 67% male, aortic valve area 1.0 ± 0.4 cm(2)) underwent cardiovascular magnetic resonance and echocardiography to assess left ventricular (LV) myocardial mass, function, and fibrosis. The indexed LV mass and measures of replacement fibrosis (late gadolinium enhancement) were associated with cTnI concentrations independent of age, sex, coronary artery disease, aortic stenosis severity, and diastolic function. In the separate Outcome Cohort, 131 patients originally recruited into the Scottish Aortic Stenosis and Lipid Lowering Trial, Impact of REgression (SALTIRE) study, had long-term follow-up for the occurrence of aortic valve replacement (AVR) and cardiovascular deaths. Over a median follow-up of 10.6 years (1178 patient-years), 24 patients died from a cardiovascular cause and 60 patients had an AVR. Plasma cTnI concentrations were associated with AVR or cardiovascular death HR 1.77 (95% CI, 1.22 to 2.55) independent of age, sex, systolic ejection fraction, and aortic stenosis severity. CONCLUSIONS: In patients with aortic stenosis, plasma cTnI concentration is associated with advanced hypertrophy and replacement myocardial fibrosis as well as AVR or cardiovascular death.

Global association of air pollution and heart failure: a systematic review and meta-analysis.

BACKGROUND: Acute exposure to air pollution has been linked to myocardial infarction, but its effect on heart failure is uncertain. We did a systematic review and meta-analysis to assess the association between air pollution and acute decompensated heart failure including hospitalisation and heart failure mortality. METHODS: Five databases were searched for studies investigating the association between daily increases in gaseous (carbon monoxide, sulphur dioxide, nitrogen dioxide, ozone) and particulate (diameter <2·5 µm [PM2·5] or <10 µm [PM10]) air pollutants, and heart failure hospitalisations or heart failure mortality. We used a random-effects model to derive overall risk estimates per pollutant. FINDINGS: Of 1146 identified articles, 195 were reviewed in-depth with 35 satisfying inclusion criteria. Heart failure hospitalisation or death was associated with increases in carbon monoxide (3·52% per 1 part per million; 95% CI 2·52-4·54), sulphur dioxide (2·36% per 10 parts per billion; 1·35-3·38), and nitrogen dioxide (1·70% per 10 parts per billion; 1·25-2·16), but not ozone (0·46% per 10 parts per billion; -0·10 to 1·02) concentrations. Increases in particulate matter concentration were associated with heart failure hospitalisation or death (PM2·5 2·12% per 10 µg/m(3), 95% CI 1·42-2·82; PM10 1·63% per 10 µg/m(3), 95% CI 1·20-2·07). Strongest associations were seen on the day of exposure, with more persistent effects for PM2·5. In the USA, we estimate that a mean reduction in PM2·5 of 3·9 µg/m(3) would prevent 7978 heart failure hospitalisations and save a third of a billion US dollars a year. INTERPRETATION: Air pollution has a close temporal association with heart failure hospitalisation and heart failure mortality. Although more studies from developing nations are required, air pollution is a pervasive public health issue with major cardiovascular and health economic consequences, and it should remain a key target for global health policy. FUNDING: British Heart Foundation.

Assessment of the capacity of vehicle cabin air inlet filters to reduce diesel exhaust-induced symptoms in human volunteers.

BACKGROUND: Exposure to particulate matter (PM) air pollution especially derived from traffic is associated with increases in cardiorespiratory morbidity and mortality. In this study, we evaluated the ability of novel vehicle cabin air inlet filters to reduce diesel exhaust (DE)-induced symptoms and markers of inflammation in human subjects. METHODS: Thirty healthy subjects participated in a randomized double-blind controlled crossover study where they were exposed to filtered air, unfiltered DE and DE filtered through two selected particle filters, one with and one without active charcoal. Exposures lasted for one hour. Symptoms were assessed before and during exposures and lung function was measured before and after each exposure, with inflammation assessed in peripheral blood five hours after exposures. In parallel, PM were collected from unfiltered and filtered DE and assessed for their capacity to drive damaging oxidation reactions in a cell-free model, or promote inflammation in A549 cells. RESULTS: The standard particle filter employed in this study reduced PM10 mass concentrations within the exposure chamber by 46%, further reduced to 74% by the inclusion of an active charcoal component. In addition use of the active charcoal filter was associated by a 75% and 50% reduction in NO2 and hydrocarbon concentrations, respectively. As expected, subjects reported more subjective symptoms after exposure to unfiltered DE compared to filtered air, which was significantly reduced by the filter with an active charcoal component. There were no significant changes in lung function after exposures. Similarly diesel exhaust did not elicit significant increases in any of the inflammatory markers examined in the peripheral blood samples 5 hour post-exposure. Whilst the filters reduced chamber particle concentrations, the oxidative activity of the particles themselves, did not change following filtration with either filter. In contrast, diesel exhaust PM passed through the active charcoal combination filter appeared less inflammatory to A549 cells. CONCLUSIONS: A cabin air inlet particle filter including an active charcoal component was highly effective in reducing both DE particulate and gaseous components, with reduced exhaust-induced symptoms in healthy volunteers. These data demonstrate the effectiveness of cabin filters to protect subjects travelling in vehicles from diesel exhaust emissions.

Effect of wood smoke exposure on vascular function and thrombus formation in healthy fire fighters.

BACKGROUND: Myocardial infarction is the leading cause of death in fire fighters and has been linked with exposure to air pollution and fire suppression duties. We therefore investigated the effects of wood smoke exposure on vascular vasomotor and fibrinolytic function, and thrombus formation in healthy fire fighters. METHODS: In a double-blind randomized cross-over study, 16 healthy male fire fighters were exposed to wood smoke (~1 mg/m³ particulate matter concentration) or filtered air for one hour during intermittent exercise. Arterial pressure and stiffness were measured before and immediately after exposure, and forearm blood flow was measured during intra-brachial infusion of endothelium-dependent and -independent vasodilators 4-6 hours after exposure. Thrombus formation was assessed using the ex vivo Badimon chamber at 2 hours, and platelet activation was measured using flow cytometry for up to 24 hours after the exposure. RESULTS: Compared to filtered air, exposure to wood smoke increased blood carboxyhaemoglobin concentrations (1.3% versus 0.8%; P < 0.001), but had no effect on arterial pressure, augmentation index or pulse wave velocity (P > 0.05 for all). Whilst there was a dose-dependent increase in forearm blood flow with each vasodilator (P < 0.01 for all), there were no differences in blood flow responses to acetylcholine, sodium nitroprusside or verapamil between exposures (P > 0.05 for all). Following exposure to wood smoke, vasodilatation to bradykinin increased (P = 0.003), but there was no effect on bradykinin-induced tissue-plasminogen activator release, thrombus area or markers of platelet activation (P > 0.05 for all). CONCLUSIONS: Wood smoke exposure does not impair vascular vasomotor or fibrinolytic function, or increase thrombus formation in fire fighters. Acute cardiovascular events following fire suppression may be precipitated by exposure to other air pollutants or through other mechanisms, such as strenuous physical exertion and dehydration.

Exposure to wood smoke increases arterial stiffness and decreases heart rate variability in humans.

BACKGROUND: Emissions from biomass combustion are a major source of indoor and outdoor air pollution, and are estimated to cause millions of premature deaths worldwide annually. Whilst adverse respiratory health effects of biomass exposure are well established, less is known about its effects on the cardiovascular system. In this study we assessed the effect of exposure to wood smoke on heart rate, blood pressure, central arterial stiffness and heart rate variability in otherwise healthy persons. METHODS: Fourteen healthy non-smoking subjects participated in a randomized, double-blind crossover study. Subjects were exposed to dilute wood smoke (mean particle concentration of 314±38 µg/m3) or filtered air for three hours during intermittent exercise. Heart rate, blood pressure, central arterial stiffness and heart rate variability were measured at baseline and for one hour post-exposure. RESULTS: Central arterial stiffness, measured as augmentation index, augmentation pressure and pulse wave velocity, was higher after wood smoke exposure as compared to filtered air (p < 0.01 for all), and heart rate was increased (p < 0.01) although there was no effect on blood pressure. Heart rate variability (SDNN, RMSSD and pNN50; p = 0.003, p < 0.001 and p < 0.001 respectively) was decreased one hour following exposure to wood smoke compared to filtered air. CONCLUSIONS: Acute exposure to wood smoke as a model of exposure to biomass combustion is associated with an immediate increase in central arterial stiffness and a simultaneous reduction in heart rate variability. As biomass is used for cooking and heating by a large fraction of the global population and is currently advocated as a sustainable alternative energy source, further studies are required to establish its likely impact on cardiovascular disease. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01488500.

Erratum to "Case Series of Triathletes with Takotsubo Cardiomyopathy Presenting with Swimming-Induced Pulmonary Edema".

[This corrects the article DOI: 10.1155/2022/3602505.].

Rationale and Design of a Randomized Controlled Pilot Trial to Assess Stent Retriever Thrombectomy for Thrombus Burden Reduction in Patients with Acute Myocardial Infarction: The RETRIEVE-AMI Study.

BACKGROUND: ST-elevation myocardial infarction (STEMI) is typically caused by thrombotic occlusion of a coronary artery with subsequent hypoperfusion and myocardial necrosis. In approximately half of patients with STEMI, despite successful restoration of epicardial coronary patency, downstream myocardium perfusion remains impeded. Coronary microvascular injury is one of the key mechanisms behind suboptimal myocardial perfusion and it is primarily, yet not exclusively, related to distal embolization of atherothrombotic material following recanalization of the culprit artery. Routine manual thrombus-aspiration has failed to show clinical efficacy in this scenario. This could be related with limitations in technology adopted as well as patients' selection. To this end, we set out to explore the efficacy and safety of stent retriever-assisted thrombectomy based on clot-removal device routinely used in stroke intervention. STUDY DESIGN AND OBJECTIVES: The stent RETRIEVEr thrombectomy for thrombus burden reduction in patients with Acute Myocardial Infarction (RETRIEVE-AMI) study has been designed to establish whether stent retriever-based thrombectomy is safe and more efficacious in thrombus modification than the current standard of care: manual thrombus aspiration or stenting. The RETRIEVE-AMI trial will enrol 81 participants admitted for primary PCI for inferior STEMI. Participants will be 1:1:1 randomised to receive either standalone PCI, thrombus aspiration and PCI, or retriever-based thrombectomy and PCI. Change in thrombus burden will be assessed via optical coherence tomography imaging. A telephone follow-up at 6 months will be arranged. CONCLUSIONS: It is anticipated by the investigators that stent retriever thrombectomy will more effectively reduce the thrombotic burden compared to current standard of care whilst being clinically safe.

Acute Response in the Noninfarcted Myocardium Predicts Long-Term Major Adverse Cardiac Events After STEMI.

BACKGROUND: Acute ST-segment elevation myocardial infarction (STEMI) has effects on the myocardium beyond the immediate infarcted territory. However, pathophysiologic changes in the noninfarcted myocardium and their prognostic implications remain unclear. OBJECTIVES: The purpose of this study was to evaluate the long-term prognostic value of acute changes in both infarcted and noninfarcted myocardium post-STEMI. METHODS: Patients with acute STEMI undergoing primary percutaneous coronary intervention underwent evaluation with blood biomarkers and cardiac magnetic resonance (CMR) at 2 days and 6 months, with long-term follow-up for major adverse cardiac events (MACE). A comprehensive CMR protocol included cine, T2-weighted, T2∗, T1-mapping, and late gadolinium enhancement (LGE) imaging. Areas without LGE were defined as noninfarcted myocardium. MACE was a composite of cardiac death, sustained ventricular arrhythmia, and new-onset heart failure. RESULTS: Twenty-two of 219 patients (10%) experienced an MACE at a median of 4 years (IQR: 2.5-6.0 years); 152 patients returned for the 6-month visit. High T1 (>1250 ms) in the noninfarcted myocardium was associated with lower left ventricular ejection fraction (LVEF) (51% ± 8% vs 55% ± 9%; P = 0.002) and higher NT-pro-BNP levels (290 pg/L [IQR: 103-523 pg/L] vs 170 pg/L [IQR: 61-312 pg/L]; P = 0.008) at 6 months and a 2.5-fold (IQR: 1.03-6.20) increased risk of MACE (2.53 [IQR: 1.03-6.22]), compared with patients with normal T1 in the noninfarcted myocardium (P = 0.042). A lower T1 (<1,300 ms) in the infarcted myocardium was associated with increased MACE (3.11 [IQR: 1.19-8.13]; P = 0.020). Both noninfarct and infarct T1 were independent predictors of MACE (both P = 0.001) and significantly improved risk prediction beyond LVEF, infarct size, and microvascular obstruction (C-statistic: 0.67 ± 0.07 vs 0.76 ± 0.06, net-reclassification index: 40% [IQR: 12%-64%]; P = 0.007). CONCLUSIONS: The acute responses post-STEMI in both infarcted and noninfarcted myocardium are independent incremental predictors of long-term MACE. These insights may provide new opportunities for treatment and risk stratification in STEMI.

Particle traps prevent adverse vascular and prothrombotic effects of diesel engine exhaust inhalation in men.

BACKGROUND: In controlled human exposure studies, diesel engine exhaust inhalation impairs vascular function and enhances thrombus formation. The aim of the present study was to establish whether an exhaust particle trap could prevent these adverse cardiovascular effects in men. METHODS AND RESULTS: Nineteen healthy volunteers (mean age, 25±3 years) were exposed to filtered air and diesel exhaust in the presence or absence of a particle trap for 1 hour in a randomized, double-blind, 3-way crossover trial. Bilateral forearm blood flow and plasma fibrinolytic factors were assessed with venous occlusion plethysmography and blood sampling during intra-arterial infusion of acetylcholine, bradykinin, sodium nitroprusside, and verapamil. Ex vivo thrombus formation was determined with the use of the Badimon chamber. Compared with filtered air, diesel exhaust inhalation was associated with reduced vasodilatation and increased ex vivo thrombus formation under both low- and high-shear conditions. The particle trap markedly reduced diesel exhaust particulate number (from 150 000 to 300 000/cm(3) to 30 to 300/cm(3); P<0.001) and mass (320±10 to 7.2±2.0 µg/m(3); P<0.001), and was associated with increased vasodilatation, reduced thrombus formation, and an increase in tissue-type plasminogen activator release. CONCLUSIONS: Exhaust particle traps are a highly efficient method of reducing particle emissions from diesel engines. With a range of surrogate measures, the use of a particle trap prevents several adverse cardiovascular effects of exhaust inhalation in men. Given these beneficial effects on biomarkers of cardiovascular health, the widespread use of particle traps on diesel-powered vehicles may have substantial public health benefits and reduce the burden of cardiovascular disease.

Case Series of Triathletes with Takotsubo Cardiomyopathy Presenting with Swimming-Induced Pulmonary Edema.

Objectives: To report three cases of triathletes who presented with swimming-induced pulmonary edema (SIPE) following water immersion. They were subsequently diagnosed with Takotsubo cardiomyopathy (TCM). Design: Retrospective case series. Method: All cases were recreational athletes competing in mass participation triathlons between June 2018 and 2019. They were initially managed by the event medical team and subsequently at the local tertiary level hospital. Written consent was gained from all the subjects. Results: The three triathletes were aged between 50 and 60 years, two were females, and all presented with acute dyspnoea on exiting the water. Two also presented with chest pain and haemoptysis. A diagnosis of SIPE was suspected by the medical event team on initial presentation of low oxygen saturations and clinical signs of pulmonary oedema. All were transferred to the local emergency department and had signs of pulmonary oedema on chest radiographs. Further investigations led to a diagnosis of TCM with findings of T wave inversion in anterolateral electrocardiogram leads and apical hypokinesia on transthoracic echocardiogram and unobstructed coronary arteries. Conclusions: This case series presents triathletes diagnosed with SIPE and TCM following the open water swim phase. It is unclear whether the myocardial dysfunction contributed to causation of SIPE or was the result of SIPE. Mass participation race organizers must be prepared that both SIPE and TCM can present in this population. Those presenting with an episode of SIPE require prompt evaluation of their cardiac and pulmonary physiology. Further research is required to ascertain the exact nature of the relationship between TCM and SIPE.

Coronary Microvascular Dysfunction Assessed by Pressure Wire and CMR After STEMI Predicts Long-Term Outcomes.

OBJECTIVES: This study sought to evaluate the long-term prognostic implications of coronary microvascular dysfunction (CMD) when assessed with both cardiovascular magnetic resonance (CMR) and index of microcirculatory resistance (IMR) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). BACKGROUND: Post-ischemic CMD can be assessed using the pressure-wire based IMR and/or by the presence of microvascular obstruction (MVO) on CMR. METHODS: A total of 198 patients with STEMI underwent IMR and MVO assessment. Patients were classified as follows: Group 1, no significant CMD (low IMR [≤40 U] and no MVO); Group 2, CMD with either high IMR (>40 U) or MVO; Group 3, CMD with both IMR >40 U and MVO. The primary endpoint was the composite of all-cause mortality, diagnosis of new heart failure, cardiac arrest, sustained ventricular tachycardia/fibrillation, and cardioverter defibrillator implantation. RESULTS: CMD with both high IMR and MVO was present in 23.7% of the cases (Group 3) and CMD with either high IMR or MVO was observed in 40.9% of cases (Group 2). At a median follow-up of 40.1 months, the primary endpoint occurred in 34 (17%) cases. At 1 year of follow-up, Group 3 (hazard ratio [HR]: 12.6; 95% confidence interval [CI]: 1.6 to 100.6; p = 0.017) but not Group 2 (HR: 7.2; 95% CI: 0.9 to 57.9; p = 0.062) had worse clinical outcomes compared with those with no significant CMD in Group 1. However, in the long-term, patients in Group 2 (HR: 4.2; 95% CI: 1.4 to 12.5; p = 0.009) and those in Group 3 (HR: 5.2; 95% CI: 1.7 to 16.2; p = 0.004) showed similar adverse outcomes, mainly driven by the occurrence of heart failure. CONCLUSIONS: Post-ischemic CMD predicts a more than 4-fold increase in long-term risk of adverse outcomes, mainly driven by the occurrence of heart failure. Defining CMD by either invasive IMR >40 U or by CMR-assessed MVO showed similar risk of adverse outcomes.

Pressure-bounded coronary flow reserve to assess the extent of microvascular dysfunction in patients with ST-elevation acute myocardial infarction.

AIMS: Assessment of microvascular function in patients with ST-elevation acute myocardial infarction (STEMI) may be useful to determine treatment strategy. The possible role of pressure-bounded coronary flow reserve (pb-CFR) in this setting has not been determined. In this study we aimed to compare pb-CFR with thermodilution-derived physiology including the index of microcirculatory resistance (IMR) and CFRthermo in a consecutive series of patients enrolled in the OxAMI study. Moreover, we aimed to assess the presence of microvascular obstruction (MVO) and myocardial injury on cardiovascular magnetic resonance (CMR) imaging performed at 48 hours and six months in STEMI patients stratified according to pb-CFR. METHODS AND RESULTS: Thermodilution-pressure-wire assessment of the infarct-related artery was performed in 148 STEMI patients before stenting and/or at completion of primary percutaneous coronary intervention (PPCI). The extent of the myocardial injury was assessed with CMR imaging at 48 hours and six months after STEMI. Post-PPCI pb-CFR was impaired (<2) and normal (>2) in 69.9% and 9.0% of the cases, respectively. In the remaining 21.1% of the patients, pb-CFR was "indeterminate". In this cohort, pb-CFR correlated poorly with thermodilution-derived coronary flow reserve (k=0.03, p=0.39). The IMR was significantly different across the pb-CFR subgroups. Similarly, significant differences were observed in MVO, myocardium area at risk and 48-hour infarct size (IS). A trend towards lower six-month IS was observed in patients with high (>2) post-PPCI pb-CFR. Nevertheless, pb-CFR was inferior to IMR in predicting MVO and the extent of IS. CONCLUSIONS: Pb-CFR can identify microvascular dysfunction in patients after STEMI. It provided superior diagnostic performance compared to thermodilution-derived CFR in predicting MVO. However, IMR was superior to both pb-CFR and thermodilution-derived CFR and, consequently, IMR was the most accurate in predicting all of the studied CMR endpoints of myocardial injury after PPCI.

Long-Term Clinical Outcomes in Patients With an Acute ST-Segment-Elevation Myocardial Infarction Stratified by Angiography-Derived Index of Microcirculatory Resistance.

Aims: Despite the prognostic value of coronary microvascular dysfunction (CMD) in patients with ST-segment-elevation myocardial infarction (STEMI), its assessment with pressure-wire-based methods remains limited due to cost, technical and procedural complexities. The non-hyperaemic angiography-derived index of microcirculatory resistance (NH IMRangio) has been shown to reliably predict microvascular injury in patients with STEMI. We investigated the prognostic potential of NH IMRangio as a pressure-wire and adenosine-free tool. Methods and Results: NH IMRangio was retrospectively derived on the infarct-related artery at completion of primary percutaneous coronary intervention (pPCI) in 262 prospectively recruited STEMI patients. Invasive pressure-wire-based assessment of the index of microcirculatory resistance (IMR) was performed. The combination of all-cause mortality, resuscitated cardiac arrest and new heart failure was the primary endpoint. NH IMRangio showed good diagnostic performance in identifying CMD (IMR > 40U); AUC 0.78 (95%CI: 0.72-0.84, p < 0.0001) with an optimal cut-off at 43U. The primary endpoint occurred in 38 (16%) patients at a median follow-up of 4.2 (2.0-6.5) years. On survival analysis, NH IMRangio > 43U (log-rank test, p < 0.001) was equivalent to an IMR > 40U(log-rank test, p = 0.02) in predicting the primary endpoint (hazard ratio comparison p = 0.91). NH IMRangio > 43U was an independent predictor of the primary endpoint (adjusted HR 2.13, 95% CI: 1.01-4.48, p = 0.047). Conclusion: NH IMRangio is prognostically equivalent to invasively measured IMR and can be a feasible alternative to IMR for risk stratification in patients presenting with STEMI.

Pre-procedural ATI score (age-thrombus burden-index of microcirculatory resistance) predicts long-term clinical outcomes in patients with ST elevation myocardial infarction treated with primary percutaneous coronary intervention.

BACKGROUND: The ATI (Age-Thrombus burden-Index of Microvascular Resistance [IMR]) score was developed to predict suboptimal myocardial reperfusion in patients with ST-Elevation Myocardial Infarction (STEMI). When applied in the early phases of revascularization (e.g. before stent insertion), it predicts which patients are most likely to have a larger infarct size. In this study, we assessed the score's utility in determining which STEMI patients are at highest risk of clinical events during follow-up. METHODS: The ATI-score was calculated prospectively in 254 STEMI patients using age (>50 years = 1 point), pre-stenting IMR (>40 U and < 100 U = 1 point; ≥100 U = 2 points) and angiographic thrombus score (4 = 1 point, 5 = 3 points); the cohort was stratified in high vs. low-intermediate ATI-score strata (≥4 vs. < 4, respectively). RESULTS: After 3 years of follow-up, patients with high ATI-score presented a higher rate of Major Adverse Cardiac Events (MACE) defined as the composite of all-cause mortality, resuscitated cardiac arrest and new heart failure diagnosis (Hazard Ratio [HR]: 3.07; 95% Confidence Interval [CI]: 1.19-7.93; p = 0.02). The ATI-score showed a moderate discriminative power (c-stat: 0.69), not significantly different from that of other risk scores used in the STEMI setting. A high ATI-score was an independent predictor of MACE (HR: 3.24; 95% CI: 1.22-8.58; p = 0.018). CONCLUSIONS: The ATI-score can discriminate patients at higher risk of long-term adverse events. The score allows predication of subsequent events even before coronary stenting, and consequently it may allow the option of individualized therapy in the early stages of the clinical care-pathway.

Angiography-derived index of microcirculatory resistance (IMRangio) as a novel pressure-wire-free tool to assess coronary microvascular dysfunction in acute coronary syndromes and stable coronary artery disease.

To investigate the diagnostic accuracy of (1) hyperaemic angiography-derived index of microcirculatory resistance (IMRangio) in defining coronary microvascular dysfunction (CMD) across patients with acute coronary syndromes (ST-elevation myocardial infarction [STEMI]; non-ST elevation acute coronary syndrome [NSTE-ACS]) and stable chronic coronary syndrome [CCS]) and (2) the accuracy of non-hyperaemic IMRangio (NH-IMRangio) to detect CMD in STEMI. 145 patients (STEMI = 66; NSTEMI = 43; CCS = 36) were enrolled. 246 pressure-wire IMR measurements were made in 189 coronary vessels. IMRangio and NH-IMRangio was derived using quantitative flow ratio. In patients with STEMI, cardiac magnetic resonance was performed to quantify microvascular obstruction (MVO). IMRangio was correlated with IMR (overall rho = 0.78, p < 0.0001; STEMI, rho = 0.85 p < 0.0001; NSTE-ACS and rho = 0.72, p < 0.0001; CCS, rho = 0.70, p < 0.0001) and demonstrated good diagnostic performance in predicting high IMR (STEMI AUCROC = 0.93 [0.88-0.98]; NSTE-ACS AUCROC = 0.77 [0.63-0.92]; CCS AUCROC = 0.88 [0.79-0.97]). Agreement between the two indices was evident on Bland Altman analysis. In STEMI, NH-IMRangio was also well correlated with IMR (rho = 0.64, p < 0.0001), with good diagnostic accuracy in predicting high invasive IMR (AUCROC = 0.82 [0.74-0.90]). Both IMRangio (AUCROC = 0.74 [0.59-0.89]) and NH-IMRangio (AUCROC = 0.76 [0.54-0.87]) were significantly associated with MVO in STEMI. In conclusions, IMRangio is a valid alternative to invasive IMR to detect CMD in patients with acute and stable coronary syndromes, whilst NH-IMRangio has a good diagnostic accuracy in STEMI where it could become a user-friendly diagnostic tool as it is adenosine-free.