Short-Term and Long-Term Risk of Recurrent Vascular Event by Cause After Ischemic Stroke in Young Adults.

Importance: Cause of ischemic stroke in young people is highly variable; however, the risk of recurrence is often presented with all subtypes of stroke grouped together in classification systems such as the Trial of ORG (danaparoid sodium [Orgaran]) 10172 in Acute Stroke Treatment (TOAST) criteria, which limits the ability to individually inform young patients with stroke about their risk of recurrence. Objective: To determine the short-term and long-term risk of recurrent vascular events after ischemic stroke at a young age by stroke cause and to identify factors associated with recurrence. Design, Setting, and Participants: This cohort study used data from the Observational Dutch Young Symptomatic Stroke Study, a prospective, multicenter, hospital-based cohort study, conducted at 17 hospitals in the Netherlands between 2013 and 2021. Eligible participants included 30-day survivors of an initial, neuroimaging-proven ischemic stroke (aged 18-49 years). Data analysis was conducted from June to July 2023. Exposure: Diagnosis of a first-ever, ischemic stroke via neuroimaging. Main Outcome and Measures: The primary outcome was short-term (within 6 months) and long-term (within 5 years) recurrence risk of any vascular event, defined as fatal or nonfatal recurrent ischemic stroke, transient ischemic attack, myocardial infarction, and revascularization procedure. Predefined characteristics were chosen to identify factors associated with risk of recurrence (cause of stroke, age, sex, stroke severity, and cardiovascular health factors). Results: A total of 1216 patients (median [IQR] age, 44.2 [38.4-47.7] years; 632 male [52.0%]; 584 female [48.0%]) were included, with a median (IQR) follow-up of 4.3 (2.6-6.0) years. The 6-month risk of any recurrent ischemic event was 6.7% (95% CI, 5.3%-8.1%), and the 5-year risk was 12.2% (95% CI, 10.2%-14.2%)The short-term risk was highest for patients with cervical artery dissections (13.2%; 95% CI, 7.6%-18.7%). Other factors associated with a recurrent short-term event were atherothrombotic stroke, rare causes of stroke, and hypertension. The long-term cumulative risk was highest for patients with atherothrombotic stroke (22.7%; 95% CI, 10.6%-34.7%) and lowest for patients with cryptogenic stroke (5.8%; 95% CI, 3.0%-8.5%). Cardioembolic stroke was associated with a recurrent long-term event, as were diabetes and alcohol abuse. Conclusions and Relevance: The findings of this cohort study of 1216 patients with an ischemic stroke at a young age suggest that the risk of recurrent vascular events was high and varied by cause of stroke both for short-term and long-term follow-up, including causes that remained concealed when combined into 1 category in the routinely used TOAST criteria. This knowledge will allow for more personalized counseling of young patients with stroke.

Association of Statins With Nonculprit Coronary Lesions and Adverse Events (from the LRP Study).

Intravascular ultrasound and near-infrared spectroscopy can identify vulnerable coronary atherosclerotic plaques. In this LRP (Lipid-Rich Plaque) substudy, we evaluated the association of statins with nonculprit lesion arterial wall lipidic content and subsequent nonculprit major adverse cardiac events. Patients from the LRP study with known statin use were included. We divided the patients into 2 cohorts-"statin therapy" and "statin-naïve"-upon presentation and then described the intravascular ultrasound and near-infrared spectroscopy analysis based on maximum 4-mm lipid core burden index (maxLCBI4mm). At 2-year follow-up, the patients' clinical events were assessed based on their statin regimen change upon discharge. Finally, patients were stratified by statin intensity based on discharge regimen. Among the 1,526 patients, 1,120 were on a statin versus 396 who were statin-naive upon presentation. Patients on a statin at baseline had a statistically higher rate of cardiovascular risk factors, patients who were statin-naive were more likely to present with an acute coronary syndrome, and the maxLCBI4mm did not differ between the 2 groups (315.67 ± 181.36 vs 325.55 ± 192.16; p = 0.359). These findings were consistent in a secondary analysis evaluating statin intensity. Patients who were switched from no statin to a statin had improved outcomes (nonculprit major adverse cardiac events) compared with patients who were on a statin at baseline without change. In conclusion, despite having a higher burden of nonlipid-related cardiac co-morbidities, patients on a statin at baseline had similar maxLCBI4mm with patients who were statin-naive, regardless of intensity. Initiating a statin at discharge provides the most benefit for events related to nonculprit lesions.

Near-infrared spectroscopy predicts events in men and women: Results from the Lipid Rich Plaque study.

Background: The Lipid Rich Plaque (LRP) study demonstrated that near-infrared spectroscopy imaging of non-obstructive lesions identified patients and segments at higher risk for subsequent non-culprit major adverse cardiac events (NC-MACE). Whether this is true for both men and women is not known. In this post hoc analysis of the LRP study, we sought to investigate whether the maximum 4-mm Lipid Core Burden Index (maxLCBI4mm) was of similar predictive value in men and women for NC-MACE. Methods: Patients with an evaluable maxLCBI4mm were stratified on the basis of sex at birth. A Cox proportional-hazards model was used to assess the predictive value of maxLCBI4mm on future NC-MACE at the patient and plaque levels. The primary endpoint was cumulative incidence of NC-MACE at 24 months. Results: Among 1271 patients, 388 (30.5%) were women. Women were older and had a higher cardiovascular risk profile. Cumulative incidence of NC-MACE at 24 months was 10.3% for women and 7.6% for men (log-rank p = 0.11). When comparing maxLCBI4mm > 400 to maxLCBI4mm ≤ 400, the hazard ratio (HR) for future NC-MACE was not significantly different between sexes: 2.10 (95% confidence interval [CI]: 1.28-3.44; p = 0.003) for men and 2.24 (95% CI: 1.18-4.28; p = 0.014) for women (p = 0.87). At the plaque level, the HR comparing maxLCBI4mm > 400 to maxLCBI4mm ≤ 400 was 3.49 (95% CI: 1.60-7.60, p = 0.002) for men and 4.79 (95% CI: 2.02-11.38, p < 0.001) for women, which was not significantly different (p = 0.57). Conclusions: The maxLCBI4mm was of similar predictive value for NC-MACE within 24 months in men and women.

Transient ST-elevation myocardial infarction versus persistent ST-elevation myocardial infarction. An appraisal of patient characteristics and functional outcome.

BACKGROUND: Up to 24% of patients presenting with ST-elevation myocardial infarction (STEMI) show resolution of ST-elevation and symptoms before revascularization. The mechanisms of spontaneous reperfusion are unclear. Given the more favorable outcome of transient STEMI, it is important to obtain further insights in differential aspects. METHODS: We compared 251 patients who presented with transient STEMI (n = 141) or persistent STEMI (n = 110). Clinical angiographic and laboratory data were collected at admission and in subset of patients additional index hemostatic data and at steady-state follow-up. Cardiac magnetic resonance imaging (CMR) was performed at 2-8 days to assess myocardial injury. RESULTS: Transient STEMI patients had more cardiovascular risk factors than STEMI patients, including more arterial disease and higher cholesterol values. Transient STEMI patients showed angiographically more often no intracoronary thrombus (41.1% vs. 2.7%, P < 0.001) and less often a high thrombus burden (9.2% vs. 40.0%, P < 0.001). CMR revealed microvascular obstruction less frequently (4.2% vs. 34.6%, P < 0.001) and smaller infarct size [1.4%; interquartile range (IQR), 0.0-3.7% vs. 8.8%; IQR, 3.9-17.1% of the left ventricle, P < 0.001] with a better preserved left ventricular ejection fraction (57.8 ± 6.7% vs. 52.5 ± 7.6%, P < 0.001). At steady state, fibrinolysis was higher in transient STEMI, as demonstrated with a reduced clot lysis time (89 ± 20% vs. 99 ± 25%, P = 0.03). CONCLUSIONS: Transient STEMI is a syndrome with less angiographic thrombus burden and spontaneous infarct artery reperfusion, resulting in less myocardial injury than STEMI. The presence of a more effective fibrinolysis in transient STEMI patients may explain these differences and might provide clues for future treatment of STEMI.

Platelet Inhibition, Endothelial Function, and Clinical Outcome in Patients Presenting With ST-Segment-Elevation Myocardial Infarction Randomized to Ticagrelor Versus Prasugrel Maintenance Therapy: Long-Term Follow-Up of the REDUCE-MVI Trial.

Background Off-target properties of ticagrelor might reduce microvascular injury and improve clinical outcome in patients with ST-segment-elevation myocardial infarction. The REDUCE-MVI (Evaluation of Microvascular Injury in Revascularized Patients with ST-Segment-Elevation Myocardial Infarction Treated With Ticagrelor Versus Prasugrel) trial reported no benefit of ticagrelor regarding microvascular function at 1 month. We now present the follow-up data up to 1.5 years. Methods and Results We randomized 110 patients with ST-segment-elevation myocardial infarction to either ticagrelor 90 mg twice daily or prasugrel 10 mg once a day. Platelet inhibition and peripheral endothelial function measurements including calculation of the reactive hyperemia index and clinical follow-up were obtained up to 1.5 years. Major adverse clinical events and bleedings were scored. An intention to treat and a per-protocol analysis were performed. There were no between-group differences in platelet inhibition and endothelial function. At 1 year the reactive hyperemia index in the ticagrelor group was 0.66±0.26 versus 0.61±0.28 in the prasugrel group (P=0.31). Platelet inhibition was lower at 1 month versus 1 year in the total study population (61% [42%-81%] versus 83% [61%-95%]; P<0.001), and per-protocol platelet inhibition was higher in patients randomized to ticagrelor versus prasugrel at 1 year (91% [83%-97%] versus 82% [65%-92%]; P=0.002). There was an improvement in intention to treat endothelial function in patients randomized to ticagrelor (P=0.03) but not in patients randomized to prasugrel (P=0.88). Major adverse clinical events (10% versus 14%; P=0.54) and bleedings (47% versus 63%; P=0.10) were similar in the intention-to-treat analysis in both groups. Conclusions Platelet inhibition at 1 year was higher in the ticagrelor group, without an accompanying increase in bleedings. Endothelial function improved over time in ticagrelor patients, while it did not change in the prasugrel group. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique Identifier: NCT02422888.

Evaluation of Microvascular Injury in Revascularized Patients With ST-Segment-Elevation Myocardial Infarction Treated With Ticagrelor Versus Prasugrel.

BACKGROUND: Despite successful restoration of epicardial vessel patency with primary percutaneous coronary intervention, coronary microvascular injury occurs in a large proportion of patients with ST-segment-elevation myocardial infarction, adversely affecting clinical and functional outcome. Ticagrelor has been reported to increase plasma adenosine levels, which might have a protective effect on the microcirculation. We investigated whether ticagrelor maintenance therapy after revascularized ST-segment-elevation myocardial infarction is associated with less coronary microvascular injury compared to prasugrel maintenance therapy. METHODS: A total of 110 patients with ST-segment-elevation myocardial infarction received a loading dose of ticagrelor and were randomized to maintenance therapy of ticagrelor (n=56) or prasugrel (n=54) after primary percutaneous coronary intervention. The primary outcome was coronary microvascular injury at 1 month, as determined with the index of microcirculatory resistance in the infarct-related artery. Cardiovascular magnetic resonance imaging was performed during the acute phase and at 1 month. RESULTS: The primary outcome of index of microcirculatory resistance was not superior in ticagrelor- or prasugrel-treated patients (ticagrelor, 21 [interquartile range, 15-39] U; prasugrel, 18 [interquartile range, 11-29] U; P=0.08). Recovery of microcirculatory resistance over time was not better in patients with ticagrelor versus prasugrel (ticagrelor, -13.9 U; prasugrel, -13.5 U; P=0.96). Intramyocardial hemorrhage was observed less frequently in patients receiving ticagrelor (23% versus 43%; P=0.04). At 1 month, no difference in infarct size was observed (ticagrelor, 7.6 [interquartile range, 3.7-14.4] g, prasugrel 9.9 [interquartile range, 5.7-16.6] g; P=0.17). The occurrence of microvascular obstruction was not different in patients on ticagrelor (28%) or prasugrel (41%; P=0.35). Plasma adenosine concentrations were not different during the index procedure and during maintenance therapy with ticagrelor or prasugrel. CONCLUSIONS: In patients with ST-segment-elevation myocardial infarction, ticagrelor maintenance therapy was not superior to prasugrel in preventing coronary microvascular injury in the infarct-related territory as assessed by the index of microcirculatory resistance, and this resulted in a comparable infarct size at 1 month. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02422888.

Effects of pacing rates on global and regional myocardial blood flow.

BACKGROUND: Information is scarce on the effects of right ventricular apical (RVA) pacing on regional and global myocardial blood flow (MBF). The purpose of this study was to assess the relationship between pacing rate and both regional and global MBF. METHODS: Four patients with exclusive atrial pacing and six patients with exclusive RVA pacing underwent three consecutive H(2) (15)O positron emission tomography scans at 60, 90, and 130 pulses per minute (ppm). For each pacing rate, regional and global MBF was determined. In all patients, the left ventricular (LV) function was normal. RESULTS: By varying the atrial pacing rate from 60 to 130 ppm, the mean global MBF increased from 0.94 to 1.40 mL/g/min, whereas the mean septal to lateral MBF ratio decreased from 1.09 to 0.83. In ventricular-paced patients at corresponding rates, the mean global MBF also increased from 1.07 to 1.52 mL/g/min but here the mean septal to lateral MBF ratio increased from 0.83 to 1.0. CONCLUSIONS: During both acute atrial and RVA pacing, regional and global MBF increases with higher pacing rates. However, the septal to lateral MBF ratio decreases with atrial pacing and increases with RVA pacing in patients with normal LV function. In RVA pacing, these different rate-dependent effects on regional MBF can be considered as a favorable factor that helps to understand why in some long-term paced patients, LV function is preserved.

Myocardial perforation by a guidewire crossing a stenotic aortic valve during cardiac catheterization.

Myocardial perforation by a guidewire after retrograde crossing of a stenotic aortic valve during cardiac catheterization is rare. We present a patient with calcific aortic stenosis who suffered this potentially life-threatening complication and in whom conservative treatment was successful. Early recognition of this complication is important for the operator performing cardiac catheterizations in patients with calcific aortic stenosis.

Myocardial perfusion SPECT identifies patients with left bundle branch block patterns at high risk for future coronary events.

BACKGROUND: The value of myocardial perfusion SPECT (MPS) for patients with left bundle branch block (LBBB) or right ventricular apical (RVA) pacing seems reduced. The prognosis of patients with only abnormal activation related perfusion defects (AARD) due to LBBB or RVA-pacing is similar to those with a normal MPS. We assessed the prognostic value of MPS in patients with LBBB or RVA pacing. METHODS: Patients with LBBB or RVA pacing referred for vasodilator stress MPS between April 2002 and January 2006 were analyzed. Group 1 are patients with normal MPS and MPS with AARD. Group 2 are patients with an MPS with a perfusion defect extending outside the AARD area. Events were cardiac death, acute myocardial infarction and coronary revascularization. RESULTS: In Group 1 (101 patients) 12 events and in Group 2 (96 patients) 45 events occurred during a mean follow-up of 2.6 +/- 1.5 years. The prognosis of Group 2 was significantly worse (49%) compared with Group 1 (91%). The annual cardiac death rate was 0.7%/year in Group 1 and 6.4%/year in Group 2 (P < .001). The prognosis of patients with LBBB was not different from those with RVA pacing. CONCLUSION: Group 2 had a significantly worse cardiac prognosis compared to Group 1. The annual cardiac death rate of <1% in Group 1 warrants a watchful waiting strategy, whereas the cardiac death rate in Group 2 warrants aggressive invasive coronary strategies.

Myocardial perfusion defects in right ventricular apical pacing are caused by partial volume effects because of wall motion abnormalities: a new model to study gated myocardial SPECT with the pacemaker on and off.

BACKGROUND: Myocardial perfusion defects have been shown in patients with abnormal intraventricular conduction. These defects have been ascribed to regional differences in myocardial blood flow caused by the abnormal activation. This proof of the concept study assesses the effects of abnormal electrical activation and subsequent wall motion abnormalities of the left ventricle on myocardial perfusion in a pacing model. METHODS: Fourteen patients with normal atrio-ventricular (AV) and intraventricular conduction with a right ventricular apical (RVA) pacemaker for brady-tachycardia syndrome were studied to allow for intrapatient comparison. Tc-sestamibi was injected in atrial inhibited (AAI) pacing mode allowing uptake during normal intraventricular conduction. Imaging was performed with AAI pacing and the second image was acquired directly after the first scan with AV pacing with a short AV-interval ensuring complete AV pacing with abnormal ventricular activation patterns (RVA pacing). Left ventricular ejection fraction (LVEF), wall motion score and myocardial perfusion score (SSS) were assessed with gated single photon emission computed tomography (SPECT) during normal conduction (AAI) and with RVA pacing. RESULTS: Left ventricular ejection fraction was normal in all patients. During AAI, three of 14 patients showed wall motion abnormalities, mean wall motion score 0.9+/-1.8 with a mean SSS 0.6+/-1.5 increasing to 4+/-6.2 and 3.6+/-5.8 (P<0.01), respectively during RVA pacing. Wall motion abnormalities were found in the apex, inferior, inferoseptal and septal walls. CONCLUSION: Despite a fixed amount of tracer activity in the myocardium, larger and more perfusion defects were visible during RVA pacing compared with normal conduction. The site and severity of the perfusion defects correlates with abnormal wall motion because of this pacing mode. This implies that abnormal wall motion is at least partly responsible for the apparent myocardial perfusion defects.

The prognostic significance of typical perfusion defects on vasodilator stress myocardial perfusion SPECT in patients with left bundle branch block or right ventricular apical pacing.

PURPOSE: Left bundle branch block (LBBB) and ventricular pacing may induce typical artefacts that appear as perfusion defects in myocardial perfusion single photon emission computed tomography (MPS). We assessed the prognosis of patients with LBBB or right ventricular apical (RVA) pacing who had chest pain and an MPS with only abnormal activation-related defects (AARD). METHODS: All patients with LBBB or ventricular pacing referred for vasodilator stress MPS between April 2002 and January 2006 were analyzed. AARD were defined as small, nontransmural, fixed defects and small reversible defects in well-defined regions always accompanied with concomitant wall motion abnormalities. RESULTS: Ninety-seven patients were included, with a mean follow-up period of 3+/-1.3 years. MPS showed AARD in 57 and it was completely normal in 40 patients. No significant difference in cumulative cardiac event-free follow-up was observed between patients with AARD (93%) and normal MPS (85%). The average annual cardiac event rate was not significantly different between the groups (1.7 and 4.3% per year, respectively). No difference was found between patients with LBBB and RVA pacing. CONCLUSION: Patients with chest pain and LBBB or RVA pacing who show AARD on MPS have a comparable prognosis as patients with abnormal activation and a normal MPS. This justifies MPS for risk stratification of patients with chest pain and LBBB or RVA pacing.

Right ventricular outflow and apical pacing comparably worsen the echocardiographic normal left ventricle.

AIMS: A depressed left ventricular function (LVF) is sometimes observed during right ventricular apical (RVA) pacing, but any prediction of this adverse effect cannot be done. Right ventricular outflow tract (RVOT) pacing is thought to deteriorate LVF less frequently because of a more normal LV activation pattern. This study aims to assess the acute effects of RVA and RVOT pacing on LVF in order to determine the contribution of echocardiography for the selection of the optimum pacing site during pacemaker (PM) implantation. METHODS AND RESULTS: Fourteen patients with a DDD-pacemaker (7 RVA, 7 RVOT) and normal LVF without other cardiac abnormalities were studied. PM dependency, because of sick sinus syndrome with normal atrioventricular and intraventricular conduction, was absent in all, allowing acute programming changes. Wall motion score (WMS), longitudinal LV strain, and tissue Doppler imaging for electromechanical delay were assessed with echocardiography during AAI pacing constituting baseline and DDD pacing. The WMS was normal at baseline (AAI pacing) in all patients and LV dyssynchrony was absent. Acute RVA and RVOT pacing deteriorated WMS, electromechanical delay, and longitudinal LV strain, but no difference of the deterioration between both pacing sites was present and dyssynchrony did not emerge. CONCLUSION: Both acute RVA and RVOT pacing negatively affect WMS, longitudinal LV strain, and mechanical activation times, without clear differences between both pacing sites. Thus echocardiographic techniques do not facilitate the selection between RVOT and RVA pacing to exclude adverse effects on LVF during PM implantation in patients with a normal LVF.

Pacemaker-related myocardial perfusion defects worsen during higher pacing rate and coronary flow augmentation.

BACKGROUND: Asynchronous activation resulting from right ventricular apical (RVA) pacing can adversely affect left ventricular function and myocardial perfusion despite normal coronary arteries. This situation makes detection of coronary heart disease in paced patients difficult. OBJECTIVES: The purpose of this study was to assess the distribution, extent, and severity of myocardial perfusion defects with RVA pacing at low and high rates and increased coronary blood flow with adenosine. METHODS: Fourteen patients with permanent RVA pacing and angiographically normal coronary arteries underwent myocardial perfusion single-photon emission computed tomography at rest at low and high pacing rates and with pacing at low rates with adenosine. Data were analyzed semi-quantitatively using a 20-segment scoring model and coded using a four-point scoring system. RESULTS: At rest, 23 (55%) of 42 coronary flow territories showed abnormal perfusion and 52 (19%) of 280 corresponding segments demonstrated abnormal perfusion; mean perfusion score was 0.22. After high-rate pacing, perfusion was abnormal in 31 (74%) of 42 flow territories and 122 (44%) of 280 segments; mean perfusion score was 0.67. Adenosine infusion resulted in 28 (67%) of 42 abnormal flow territories and 90 (32%) of 280 abnormal segments; mean perfusion score was 0.44. Perfusion defects were observed most often in close proximity to the origin of the pacing site. CONCLUSION: RVA pacing results in myocardial perfusion defects. The false-positive findings are present at rest and more obvious with high-rate pacing than during adenosine infusion. Detection of coronary artery disease should be performed with caution in RVA paced patients because of the high number of perfusion defects observed in the absence of coronary artery disease.