Ultra-low-dose CT versus chest X-ray for patients suspected of pulmonary disease at the emergency department: a multicentre randomised clinical trial.

BACKGROUND: Chest CT displays chest pathology better than chest X-ray (CXR). We evaluated the effects on health outcomes of replacing CXR by ultra-low-dose chest-CT (ULDCT) in the diagnostic work-up of patients suspected of non-traumatic pulmonary disease at the emergency department. METHODS: Pragmatic, multicentre, non-inferiority randomised clinical trial in patients suspected of non-traumatic pulmonary disease at the emergency department. Between 31 January 2017 and 31 May 2018, every month, participating centres were randomly allocated to using ULDCT or CXR. Primary outcome was functional health at 28 days, measured by the Short Form (SF)-12 physical component summary scale score (PCS score), non-inferiority margin was set at 1 point. Secondary outcomes included hospital admission, hospital length of stay (LOS) and patients in follow-up because of incidental findings. RESULTS: 2418 consecutive patients (ULDCT: 1208 and CXR: 1210) were included. Mean SF-12 PCS score at 28 days was 37.0 for ULDCT and 35.9 for CXR (difference 1.1; 95% lower CI: 0.003). After ULDCT, 638/1208 (52.7%) patients were admitted (median LOS of 4.8 days; IQR 2.1-8.8) compared with 659/1210 (54.5%) patients after CXR (median LOS 4.6 days; IQR 2.1-8.8). More ULDCT patients were in follow-up because of incidental findings: 26 (2.2%) versus 4 (0.3%). CONCLUSIONS: Short-term functional health was comparable between ULDCT and CXR, as were hospital admissions and LOS, but more incidental findings were found in the ULDCT group. Our trial does not support routine use of ULDCT in the work-up of patients suspected of non-traumatic pulmonary disease at the emergency department. TRIAL REGISTRATION NUMBER: NTR6163.

The Dynamic Relationship Between Invasive Microvascular Function and Microvascular Injury Indicators, and Their Association With Left Ventricular Function and Infarct Size at 1-Month After Reperfused ST-Segment-Elevation Myocardial Infarction.

BACKGROUND: The invasive microvascular function indices, coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR), exhibit a dynamic pattern after ST-segment-elevation myocardial infarction. The effects of microvascular injury on the evolution of the microvascular function and the prognostic significance of the evolution of microvascular function are unknown. We investigated the relationship between the temporal changes of CFR and IMR, and cardiovascular magnetic resonance-derived microvascular injury characteristics in reperfused ST-segment-elevation myocardial infarction patients, and their association with 1-month left ventricular ejection fraction and infarct size (IS). METHODS: In 109 ST-segment-elevation myocardial infarction patients who underwent angiography for primary percutaneous coronary intervention (PPCI) and at 1-month follow-up, invasive assessment of CFR and IMR were performed in the culprit artery during both procedures. Cardiovascular magnetic resonance was performed 2 to 7 days after PPCI and at 1 month and provided assessment of left ventricular ejection fraction, IS, microvascular obstruction, and intramyocardial hemorrhage. RESULTS: CFR and IMR significantly changed over 1 month (both, P<0.001). The absolute IMR change over 1 month (ΔIMR) showed association with both microvascular obstruction and intramyocardial hemorrhage presence (both, P=0.01). ΔIMR differed between patients with/without microvascular obstruction (P=0.02) and with/without intramyocardial hemorrhage (P=0.04) but not ΔCFR for both. ΔIMR demonstrated association with both left ventricular ejection fraction and IS at 1 month (P<0.001, P=0.001, respectively), but not ΔCFR for both. Receiver-operating characteristics curve analysis of ΔIMR showed a larger area under the curve than post-PPCI CFR and IMR, and ΔCFR to be associated with both 1-month left ventricular ejection fraction >50% and extensive IS (the highest quartile). CONCLUSIONS: In reperfused ST-segment-elevation myocardial infarction patients, CFR and IMR significantly improved 1 month after PPCI; the temporal change in IMR is closely related to the presence/absence of microvascular damage and IS. ΔIMR exhibits a stronger association for 1-month functional outcome than post-PPCI CFR, IMR, or ΔCFR.

Feasibility of sonothrombolysis in the ambulance for ST-elevation myocardial infarction.

Patients with ST-elevation myocardial infarction (STEMI) due to coronary occlusion require immediate restoration of epicardial and microvascular blood flow. A potentially new reperfusion method is the use of ultrasound and microbubbles, also called sonothrombolysis. The oscillation and collapse of intravenously administered microbubbles upon exposure to high mechanical index (MI) ultrasound pulses results in thrombus dissolution and stimulates nitric oxide-mediated increases in tissue perfusion. The aim of this study was to assess feasibility of sonothrombolysis in the ambulance for STEMI patients. Patients presenting with chest pain and ST-elevations on initial electrocardiogram were included. Sonothrombolysis was applied in the ambulance during patient transfer to the percutaneous coronary intervention (PCI) center. Feasibility was assessed based on duration of sonothrombolysis treatment and number of high MI pulses applied. Vital parameters, ST-resolution, pre- and post-PCI coronary flow and cardiovascular magnetic resonance images were analyzed. Follow up was performed at six months after STEMI. Twelve patients were screened, of which three patients were included in the study. Sonothrombolysis duration and number of high MI pulses ranged between 12 and 17 min and 32-60 flashes respectively. No arrhythmias or changes in vital parameters were observed during and directly after sonothrombolysis, although one patient developed in-hospital ventricular fibrillation 20 min after sonothrombolysis completion but before PCI. In one case, sonothrombolysis on top of regular pre-hospital care resulted in reperfusion before PCI. This is the first report on the feasibility of performing sonothrombolysis to treat myocardial infarction in an ambulance. To assess efficacy and safety of pre-hospital sonothrombolysis, clinical trials with greater patient numbers should be performed. EU Clinical Trials Register (identifier: 2019-001883-31), registered 2020-02-25.

Functional recovery after percutaneous revascularization of coronary chronic total occlusions: insights from cardiac magnetic resonance tissue tracking.

To evaluate the effect of percutaneous coronary intervention (PCI) of coronary chronic total occlusions (CTOs) on left ventricular (LV) strain assessed using cardiac magnetic resonance (CMR) tissue tracking. In 150 patients with a CTO, longitudinal (LS), radial (RS) and circumferential shortening (CS) were determined using CMR tissue tracking before and 3 months after successful PCI. In patients with impaired LV strain at baseline, global LS (10.9 ± 2.4% vs 11.6 ± 2.8%; P = 0.006), CS (11.3 ± 2.9% vs 12.0 ± 3.5%; P = 0.002) and RS (15.8 ± 4.9% vs 17.4 ± 6.6%; P = 0.001) improved after revascularization of the CTO, albeit to a small, clinically irrelevant, extent. Strain improvement was inversely related to the extent of scar, even after correcting for baseline strain (B = - 0.05; P = 0.008 for GLS, B = - 0.06; P = 0.016 for GCS, B = - 0.13; P = 0.017 for GRS). In the vascular territory of the CTO, dysfunctional segments showed minor improvement in both CS (10.8 [6.9 to 13.3] % vs 11.9 [8.1 to 15.0] %; P < 0.001) and RS (14.2 [8.4 to 18.7] % vs 16.0 [9.9 to 21.8] %; P < 0.001) after PCI. Percutaneous revascularization of CTOs does not lead to a clinically relevant improvement of LV function, even in the subgroup of patients and segments most likely to benefit from revascularization (i.e. LV dysfunction at baseline and no or limited myocardial scar).

Viability and functional recovery after chronic total occlusion percutaneous coronary intervention.

OBJECTIVES: This study evaluated myocardial viability as well as global and regional functional recovery after successful chronic coronary total occlusion (CTO) percutaneous coronary intervention (PCI) using sequential quantitative cardiac magnetic resonance (CMR) imaging. BACKGROUND: The patient benefits of CTO PCI are being questioned. METHODS: In a single high-volume CTO PCI center patients were prospectively scheduled for CMR at baseline and 3 months after successful CTO PCI between 2013 and 2018. Segmental wall thickening (SWT) and percentage late gadolinium enhancement (LGE) were quantitatively measured per segment. Viability was defined as dysfunctional myocardium (<2.84 mm SWT) with no or limited scar (≤50% LGE). RESULTS: A total of 132 patients were included. Improvement of left ventricular ejection fraction was modest after CTO PCI (from 48.1 ± 11.8 to 49.5 ± 12.1%, p < 0.01). CTO segments with viability (N = 216, [31%]) demonstrated a significantly higher increase in SWT (0.80 ± 1.39 mm) compared to CTO segments with pre-procedural preserved function (N = 456 [65%], 0.07 ± 1.43 mm, p < 0.01) or extensive scar (LGE >50%, N = 26 [4%], -0.08 ± 1.09 mm, p < 0.01). Patients with ≥2 CTO segments viability showed more SWT increase in the CTO territory compared to patients with 0-1 segment viability (0.49 ± 0.93 vs. 0.12 ± 0.98 mm, p = 0.03). CONCLUSIONS: Detection of dysfunctional myocardial segments without extensive scar (≤50% LGE) as a marker for viability on CMR aids in identifying patients with significant regional functional recovery after CTO PCI.

The effect of immediate coronary angiography after cardiac arrest without ST-segment elevation on left ventricular function. A sub-study of the COACT randomised trial.

BACKGROUND: The effect of immediate coronary angiography and percutaneous coronary intervention (PCI) in patients who are successfully resuscitated after cardiac arrest in the absence of ST-segment elevation myocardial infarction (STEMI) on left ventricular function is currently unknown. METHODS: This prespecified sub-study of a multicentre trial evaluated 552 patients, successfully resuscitated from out-of-hospital cardiac arrest without signs of STEMI. Patients were randomized to either undergo immediate coronary angiography or delayed coronary angiography, after neurologic recovery. All patients underwent PCI if indicated. The main outcomes of this analysis were left ventricular ejection fraction and end-diastolic and systolic volumes assessed by cardiac magnetic resonance imaging or echocardiography. RESULTS: Data on left ventricular function was available for 397 patients. The mean (± standard deviation) left ventricular ejection fraction was 45.2% (±12.8) in the immediate angiography group and 48.4% (±13.2) in the delayed angiography group (mean difference: -3.19; 95% confidence interval [CI], -6.75 to 0.37). Median left ventricular end-diastolic volume was 177 ml in the immediate angiography group compared to 169 ml in the delayed angiography group (ratio of geometric means: 1.06; 95% CI, 0.95-1.19). In addition, mean left ventricular end-systolic volume was 90 ml in the immediate angiography group compared to 78 ml in the delayed angiography group (ratio of geometric means: 1.13; 95% CI 0.97-1.32). CONCLUSION: In patients successfully resuscitated after out-of-hospital cardiac arrest and without signs of STEMI, immediate coronary angiography was not found to improve left ventricular dimensions or function compared with a delayed angiography strategy. CLINICAL TRIAL REGISTRATION: Netherlands Trial Register number, NTR4973.

Dynamic left ventricular outflow tract obstruction in Takotsubo cardiomyopathy resulting in cardiogenic shock.

We report a case of a 73-year-old female patient, who was admitted to the coronary care unit due to chest pain, malaise and near syncope. During physical examination, the patient was hypotensive and there were signs of left-sided heart failure and a loud systolic murmur. Echocardiogram showed apical ballooning with dynamic left ventricular outflow tract obstruction, based on systolic anterior motion of the mitral valve with important mitral valve regurgitation. In the acute setting, the cardiogenic shock was treated cautiously with fluid resuscitation and intravenous metoprolol, resulting in direct stabilisation of her haemodynamic condition. As a codiagnosis, there was a significant stenosis of left anterior descending artery, which was treated successfully by percutaneous coronary intervention with drug eluting stents. During follow-up, left ventricular function normalised, and the left ventricular outflow tract obstruction, systolic anterior motion of mitral valve and related mitral regurgitation all resolved.

Coronary collaterals and myocardial viability in patients with chronic total occlusions.

AIMS: This study aimed to evaluate associations between coronary collaterals and myocardial viability as assessed by quantitative cardiac magnetic resonance (CMR) imaging in patients with a chronic coronary total occlusion (CTO). METHODS AND RESULTS: A total of 218 patients with a CTO who underwent CMR between 2013 and 2018 were included. A concomitant collateral connection (CC) score 2 and Rentrop grade 3 defined well-developed collaterals in 146 (67%) patients, whereas lower CC scores or Rentrop grades characterised poorly developed collaterals. Dysfunctional myocardium (<3 mm segmental wall thickening [SWT]) and ≤50% late gadolinium enhancement (LGE) defined viability. Extensive scar (LGE >50%) was observed in only 5% of CTO segments. In the CTO territory, SWT was greater (3.72±1.51 vs 3.05±1.60 mm, p<0.01) and the extent of scar was less (7.0 [0.1-16.7] vs 13.1% [2.8-22.2], p=0.048) in patients having well-developed versus poorly developed collaterals. Viability was more prevalent in CTO segments among patients with poorly developed versus well-developed collaterals (44% vs 30% of segments, p<0.01), predominantly due to a higher prevalence of dysfunctional myocardium (51% vs 34% of segments, p<0.01) in the poorly developed collateral group. CONCLUSIONS: The infarcted area in myocardium subtended by a CTO is generally limited. Well-developed collaterals are associated with less myocardial scar and enhanced preserved function. However, viability was regularly present in patients with poorly developed collaterals.

Mismatch Between Cardiac Magnetic Resonance Imaging and Invasive Physiology.

A 74-year-old man returned to the clinic for follow-up of residual nonculprit lesions after reperfused acute inferior ST-segment elevation myocardial infarction. Stress cardiac magnetic resonance perfusion imaging demonstrated a severe perfusion defect in the anterior wall. Surprisingly, subsequent invasive assessment did not reveal hemodynamically significant obstruction in the nonculprit vessels. (Level of Difficulty: Beginners.).

Cardiac Magnetic Resonance for Evaluating Nonculprit Lesions After Myocardial Infarction: Comparison With Fractional Flow Reserve.

OBJECTIVES: This study sought to determine the agreement between cardiac magnetic resonance (CMR) imaging and invasive measurements of fractional flow reserve (FFR) in the evaluation of nonculprit lesions after ST-segment elevation myocardial infarction (STEMI). In addition, we investigated whether fully quantitative analysis of myocardial perfusion is superior to semiquantitative and visual analysis. BACKGROUND: The agreement between CMR and FFR in the evaluation of nonculprit lesions in patients with STEMI with multivessel disease is unknown. METHODS: Seventy-seven patients with STEMI with at least 1 intermediate (diameter stenosis 50% to 90%) nonculprit lesion underwent CMR and invasive coronary angiography in conjunction with FFR measurements at 1 month after primary intervention. The imaging protocol included stress and rest perfusion, cine imaging, and late gadolinium enhancement. Fully quantitative, semiquantitative, and visual analysis of myocardial perfusion were compared against a reference of FFR. Hemodynamically obstructive was defined as FFR ≤0.80. RESULTS: Hemodynamically obstructive nonculprit lesions were present in 31 (40%) patients. Visual analysis displayed an area under the curve (AUC) of 0.74 (95% confidence interval [CI]: 0.62 to 0.83), with a sensitivity of 73% and a specificity of 70%. For semiquantitative analysis, the relative upslope of the stress signal intensity time curve and the relative upslope derived myocardial flow reserve had respective AUCs of 0.66 (95% CI: 0.54 to 0.77) and 0.71 (95% CI: 0.59 to 0.81). Fully quantitative analysis did not augment diagnostic performance (all p > 0.05). Stress myocardial blood flow displayed an AUC of 0.76 (95% CI: 0.64 to 0.85), with a sensitivity of 69% and a specificity of 77%. Similarly, MFR displayed an AUC of 0.82 (95% CI: 0.71 to 0.90), with a sensitivity of 82% and a specificity of 71%. CONCLUSIONS: CMR and FFR have moderate-good agreement in the evaluation of nonculprit lesions in patients with STEMI with multivessel disease. Fully quantitative, semiquantitative, and visual analysis yield similar diagnostic performance.

Cardiovascular magnetic resonance techniques for tissue characterization after acute myocardial injury.

The annual incidence of hospital admission for acute myocardial infarction lies between 90 and 312 per 100 000 inhabitants in Europe. Despite advances in patient care 1 year mortality after ST-segment elevation myocardial infarction (STEMI) remains around 10%. Cardiovascular magnetic resonance imaging (CMR) has emerged as a robust imaging modality for assessing patients after acute myocardial injury. In addition to accurate assessment of left ventricular ejection fraction and volumes, CMR offers the unique ability of visualization of myocardial injury through a variety of imaging techniques such as late gadolinium enhancement and T2-weighted imaging. Furthermore, new parametric mapping techniques allow accurate quantification of myocardial injury and are currently being exploited in large trials aiming to augment risk management and treatment of STEMI patients. Of interest, CMR enables the detection of microvascular injury (MVI) which occurs in approximately 40% of STEMI patients and is a major independent predictor of mortality and heart failure. In this article, we review traditional and novel CMR techniques used for myocardial tissue characterization after acute myocardial injury, including the detection and quantification of MVI. Moreover, we discuss clinical scenarios of acute myocardial injury in which the tissue characterization techniques can be applied and we provide proposed imaging protocols tailored to each scenario.

Long-term follow-up of the viability guided angioplasty after acute myocardial infarction (VIAMI) trial.

BACKGROUND: Patients with ST-elevation myocardial infarction (STEMI) not treated with primary or rescue percutaneous coronary intervention (PCI) are at risk for recurrent ischemia. In non-high risk patients, with proven viability in the infarct-area, the VIAMI trial showed benefit of early in-hospital stenting of the infarct-related coronary artery for the composite of death, myocardial infarction (MI), or unstable angina (UA) at 1 year follow-up. In this study we evaluated the long-term outcome (median 8 years) of patients included in the VIAMI-trial. METHODS: After being stable during the first 48 h of their acute MI, we randomly assigned 216 patients with viability to an invasive (PCI) or a conservative (ischemia-guided) strategy. The primary outcome was the composite endpoint of death from any cause, recurrent myocardial infarction, or unstable angina. The secondary outcome of this study was the need for (repeat) revascularization. RESULTS: The combined endpoint of death, recurrent MI and UA was 20.8% in the invasive group and 32.7% in the conservative group (hazard ratio 0.59; 95% CI 0.36-0.99, p = 0.049). No differences were seen in death (8.5% vs. 8.2%, p = 0.80) or MI (7.5% vs. 10.9%, p = 0.48). Only UA showed a significant difference (4.7% vs. 13.6%, p = 0.002). Repeated revascularization was performed in 22.6% of the invasive group and 41.8% of the conservative group (hazard ratio 0.43; 95% CI 0.29-0.74, p < 0.001).` CONCLUSION: In patients with acute MI (treated with thrombolysis or without reperfusion therapy) and proven viability in the infarct-area, we demonstrated a long-term benefit of early in-hospital stenting of the infarct-related coronary artery.

Left ventricular remodeling after acute myocardial infarction: the influence of viability and revascularization - an echocardiographic substudy of the VIAMI-trial.

BACKGROUND: Viability seems to be important in preventing ventricular remodeling after acute myocardial infarction (AMI). We investigated the influence of viability, as demonstrated with low-dose dobutamine echocardiography, and the role of early revascularization on the process of left ventricular (LV) remodeling after AMI. METHODS: We retrospectively investigated 224 patients who were initially included in the viability-guided angioplasty after acute myocardial infarction-trial (VIAMI-trial). Patients in the VIAMI-trial did not undergo a primary or rescue percutaneous coronary intervention and were stable in the early in-hospital phase. Patients underwent viability testing within 72 hours after AMI. Patients with viability were randomized to an invasive strategy or an ischemia-guided strategy. Follow-up echocardiography was performed at a mean of 205 days. In this echocardiographic substudy, patients were divided into three new groups: group 1, viable and revascularized before follow-up echocardiogram; group 2, viable, but medically treated; and group 3, non-viable patients. RESULTS: Group 1 showed preservation of LV volume indices. The ejection fraction (EF) increased significantly from 54.0% to 57.5% (P = 0.047). Group 2 showed a significant increase in LV volume indices with no improvement in EF (53.3% versus 53.0%, P = 0.86). Group 3 showed a significant increase in LV volume indices, with a decrease in EF from 53.5% to 49.1% (P = 0.043). Multivariate logistic regression analysis indicated the number of viable segments and revascularization during follow-up as independent predictors for EF improvement, especially in patients with lower EF at baseline. CONCLUSION: Viability early after AMI is associated with improvement in LV function after revascularization. When viable myocardium is not revascularized, the LV tends to remodel with increased LV volumes, without improvement of EF. Absence of viability results in ventricular dilatation and deterioration of EF, irrespective of revascularization status. TRIAL REGISTRATION: NCT00149591 (assigned: 6 September 2005).

Improved clinical outcome after invasive management of patients with recent myocardial infarction and proven myocardial viability: primary results of a randomized controlled trial (VIAMI-trial).

BACKGROUND: Patients with ST-elevation myocardial infarction (STEMI) not treated with primary or rescue percutaneous coronary intervention (PCI) are at risk for recurrent ischemia, especially when viability in the infarct-area is present. Therefore, an invasive strategy with PCI of the infarct-related coronary artery in patients with viability would reduce the occurrence of a composite end point of death, reinfarction, or unstable angina (UA). METHODS: Patients admitted with an (sub)acute myocardial infarction, who were not treated by primary or rescue PCI, and who were stable during the first 48 hours after the acute event, were screened for the study. Eventually, we randomly assigned 216 patients with viability (demonstrated with low-dose dobutamine echocardiography) to an invasive or a conservative strategy. In the invasive strategy stenting of the infarct-related coronary artery was intended with abciximab as adjunct treatment. Seventy-five (75) patients without viability served as registry group. The primary endpoint was the composite of death from any cause, recurrent myocardial infarction (MI) and unstable angina at one year. As secondary endpoint the need for (repeat) revascularization procedures and anginal status were recorded. RESULTS: The primary combined endpoint of death, recurrent MI and unstable angina was 7.5% (8/106) in the invasive group and 17.3% (19/110) in the conservative group (Hazard ratio 0.42; 95% confidence interval [CI] 0.18-0.96; p = 0.032). During follow up revascularization-procedures were performed in 6.6% (7/106) in the invasive group and 31.8% (35/110) in the conservative group (Hazard ratio 0.18; 95% CI 0.13-0.43; p < 0.0001). A low rate of recurrent ischemia was found in the non-viable group (5.4%) in comparison to the viable-conservative group (14.5%). (Hazard-ratio 0.35; 95% CI 0.17-1.00; p = 0.051). CONCLUSION: We demonstrated that after acute MI (treated with thrombolysis or without reperfusion therapy) patients with viability in the infarct-area benefit from a strategy of early in-hospital stenting of the infarct-related coronary artery. This treatment results in a long-term uneventful clinical course. The study confirmed the low risk of recurrent ischemia in patients without viability. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00149591.

Early and long-term outcome of elective stenting of the infarct-related artery in patients with viability in the infarct-area: Rationale and design of the Viability-guided Angioplasty after acute Myocardial Infarction-trial (The VIAMI-trial).

BACKGROUND: Although percutaneous coronary intervention (PCI) is becoming the standard therapy in ST-segment elevation myocardial infarction (STEMI), to date most patients, even in developed countries, are reperfused with intravenous thrombolysis or do not receive a reperfusion therapy at all. In the post-lysis period these patients are at high risk for recurrent ischemic events. Early identification of these patients is mandatory as this subgroup could possibly benefit from an angioplasty of the infarct-related artery.Since viability seems to be related to ischemic adverse events, we initiated a clinical trial to investigate the benefits of PCI with stenting of the infarct-related artery in patients with viability detected early after acute myocardial infarction. METHODS: The VIAMI-study is designed as a prospective, multicenter, randomized, controlled clinical trial. Patients who are hospitalized with an acute myocardial infarction and who did not have primary or rescue PCI, undergo viability testing by low-dose dobutamine echocardiography (LDDE) within 3 days of admission. Consequently, patients with demonstrated viability are randomized to an invasive or conservative strategy. In the invasive strategy patients undergo coronary angiography with the intention to perform PCI with stenting of the infarct-related coronary artery and concomitant use of abciximab. In the conservative group an ischemia-guided approach is adopted (standard optimal care).The primary end point is the composite of death from any cause, reinfarction and unstable angina during a follow-up period of three years. CONCLUSION: The primary objective of the VIAMI-trial is to demonstrate that angioplasty of the infarct-related coronary artery with stenting and concomitant use of abciximab results in a clinically important risk reduction of future cardiac events in patients with viability in the infarct-area, detected early after myocardial infarction.