Risk of recurrent stroke and mortality after cryptogenic stroke in diabetic patients.

BACKGROUND: Diabetes mellitus is a highly prevalent and growing chronic disease that is associated with increased risk of recurrence among several stroke subtypes. However, evidence on the prognostic role of diabetes in the setting of cryptogenic stroke (CS) remains scarce. METHODS: From April 2019 to November 2021, we recruited prospectively 78 consecutive patients with CS. Patients were classified according to the presence of diabetes. Main outcome was the composite of stroke recurrence and death. Secondary outcome was stroke recurrence. RESULTS: Mean age of the cohort was 78 ± 7.7 years and 18 patients (23%) had diabetes. After a median clinical follow-up of 23 months the incidence of stroke recurrence and mortality [HR 5.8 (95% CI 1.9-19), p = 0.002] and the incidence of stroke recurrence [HR 16.6 (95% CI 1.8-149), p = 0.012], were higher in patients with diabetes. After adjusting for potential confounders diabetes was identified as an independent predictor of stroke recurrence and death in patients with CS [HR 33.8 (95% CI 2.1-551), p = 0.013]. Other independent predictors of stroke recurrence and mortality were hypertension [HR 31.4 (95% CI 1.8-550), p = 0.018], NTproBNP [HR 1.002 (95% CI 1.001-1.004), p = 0.013] and chronic kidney disease (CKD) [HR 27.4 (95% CI 1.4-549) p = 0.03]. Furthermore, diabetes was an independent predictor of stroke recurrence [HR 103 (95% CI 1.3-8261), p = 0.038]. CONCLUSION: Diabetic patients with CS are at higher risk of stroke recurrence and death. Hypertension CKD and NTproBNP are also independent predictors of stroke recurrence and death after CS.

Electrocardiogram and CMR to differentiate tachycardia-induced cardiomyopathy from dilated cardiomyopathy in patients admitted for heart failure.

In patients admitted for heart failure (HF) with reduced left ventricular ejection fraction (LVEF) and a concomitant supraventricular tachyarrhythmia (SVT) it is a challenge to predict LVEF recovery and differentiate tachycardia-induced cardiomyopathy (TIC) from dilated cardiomyopathy (DCM). The role of the electrocardiogram (ECG) and cardiac magnetic resonance (CMR) and in this acute setting remains unsettled. Forty-three consecutive patients admitted for HF due to SVT and LVEF < 50% undergoing CMR in the acute phase, were retrospectively included. Those who had LVEF > 50% at follow up were classified as TIC and those with LVEF < 50% were classified as DCM. Clinical, CMR and ECG findings were analyzed to predict LVEF recovery. Twenty-five (58%) patients were classified as TIC. Patients with DCM had wider QRS (121.2 ± 26 vs 97.7 ± 17.35 ms; p = 0.003). On CRM the TIC group presented with higher LVEF (33.4 ± 11 vs 26.9 ± 6.4%; p = 0.019) whereas late gadolinium enhancement (LGE) was more frequent in DCM group (61 vs 16%; p = 0.004). On multivariate analysis, QRS duration ≥ 100 ms (p = 0.027), LVEF < 40% on CMR (p = 0.047) and presence of LGE (p = 0.03) were independent predictors of lack of LVEF recovery. Furthermore, during follow-up (median 60 months) DCM patients were admitted more frequently for HF (44 vs 0%; p < 0.001) than TIC patients. In patients with reduced LVEF admitted for HF due to SVT, QRS ≥ 100 ms, LVEF < 40% and LGE are independently associated with lack of LVEF recovery and worse clinical outcome.

A Comprehensive Model to Predict Atrial Fibrillation in Cryptogenic Stroke: The Decryptoring Score.

OBJETIVE: Cryptogenic stroke (CS) represents up to 30% of ischemic strokes (IS). Since atrial fibrillation (AF) can be detected in up to 30% of CS, there is a clinical need for estimating the probability of underlying AF in CS to guide the optimal secondary prevention strategy. The aim of the study was to develop the first comprehensive predictive score including clinical conditions, biomarkers, and left atrial strain (LAS), to predict AF detection in this setting. METHODS: Sixty-three consecutive patients with IS or transient ischemic attack with ABCD2 scale ≥ 4 of unknown etiology were prospectively recruited. Clinical, laboratory, and echocardiographic variables were collected. All patients underwent 15 days wearable Holter-ECG monitoring. Main objective was the Decryptoring score creation to predict AF in CS. Score variables were selected by a univariate analysis and, thereafter, score points were derived according to a multivariant analysis. RESULTS: AF was detected in 15 patients (24%). Age > 75 (9 points), hypertension (1 point), Troponin T > 40 ng/L (8.5 points), NTproBNP > 200 pg/ml (0.5 points), LAS reservoir < 25.3% (24.5 points) and LAS conduct < 10.4% (0.5 points) were included in the score. The rate of AF detection was 0% among patients with a score of < 10 and 80% among patients with a score > 35. The comparison of the predictive validity between the proposed score and AF-ESUS score resulted in an AUC of 0.94 for Decryptoring score and of 0.65 for the AF-ESUS score(p < 0.001). CONCLUSION: This novel score offers an accurate AF prediction in patients with CS; however these results will require validation in an independent cohort using this model before they may be translated into clinical practice.

Baseline CHA2 DS2 -VASc score and prognosis in octogenarians with non-ST segment elevation acute coronary syndrome.

BACKGROUND: CHA2 DS2 -VASc Score is widely used to predict thromboembolic risk in patients with Atrial Fibrillation (AF). We sought to study if this score predicts outcomes in elderly patients with Non-ST segment Elevation Acute Coronary Syndromes (NSTEACS). METHODS: The multicenter LONGEVO-SCA prospective registry included 532 unselected patients with NSTEACS aged ≥80 years. Data to calculate CHA2 DS2 -VASc Score were available in 523 patients (98.3%). They were classified according to CHA2 DS2 -VASc Score: group 1 (score ≤ 4), and 2 (5-9). We studied outcomes in terms of mortality or readmission at 6 months follow-up. RESULTS: A total of 266 patients (51%) had a high CHA2 DS2 -VASc Score (group 2). They were more often women, with more cardiovascular risk factors, such as hypertension or diabetes mellitus, and history of previous stroke and cardiovascular disease and heart failure (all, P = .001). Geriatric syndromes (Barthel Index, Lawton Brody, cognitive impairment, and frailty) and Charlson Index were worse in this group (all, P = .001). They had poorer clinical status on admission, with worse Killip class and lower left ventricle ejection fraction (all, P = .001), and developed new-onset AF more often during admission (12.4% vs. 6.6%, P = .024). At six months follow-up, patients in group 2 had higher reinfarction, all-cause mortality, and mortality or readmission rates. A CHA2 DS2 -VASc Score > 4 was associated with mortality or readmission at 6 months (HR 2.07, P < .001). However, after adjusting for potential confounders, this last association was not significant (P = .175). CONCLUSIONS: A CHA2 DS2 -VASc Score > 4 is present in half of octogenarians with NSTEACS and is associated with poorer outcomes. However, it is not an independent predictor of events and should not replace recommended tools for risk prediction in this setting.

Laser-interstitial thermal therapy compared to craniotomy for treatment of radiation necrosis or recurrent tumor in brain metastases failing radiosurgery.

PURPOSE: Many publications report laser-interstitial thermal therapy (LITT) as a viable alternative treatment to craniotomy for radiation necrosis (RN) and re-growing tumor occurring after stereotactic radiosurgery (SRS) for brain metastases. No studies to-date have compared the two options. The aim of this study was to retrospectively compare outcomes after LITT versus craniotomy for regrowing lesions in patients previously treated with SRS for brain metastases. METHODS: Data were collected from a single-institution chart review of patients treated with LITT or craniotomy for previously irradiated brain metastasis. RESULTS: Of 75 patients, 42 had recurrent tumor (56%) and 33 (44%) had RN. Of patients with tumor, 26 underwent craniotomy and 16 LITT. For RN, 15 had craniotomy and 18 LITT. There was no significant difference between LITT and craniotomy in ability to taper off steroids or neurological outcomes. Progression-free survival (PFS) and overall survival (OS) were similar for LITT versus craniotomy, respectively: %PFS-survival at 1-year = 72.2% versus 61.1%, %PFS-survival at 2-years = 60.0% versus 61.1%, p = 0.72; %OS-survival at 1-year = 69.0% versus 69.3%, %OS-survival at 2-years = 56.6% versus 49.5%, p = 0.90. Craniotomy resulted in higher rates of pre-operative deficit improvement than LITT (p < 0.01). On subgroup analysis, the single factor most significantly associated with OS and PFS was pathology of the lesion. About 40% of tumor lesions needed post-operative salvage with radiation after both craniotomy and LITT. CONCLUSIONS: LITT was as efficacious as craniotomy in achieving local control of recurrent irradiated brain metastases and facilitating steroid taper, regardless of pathology. Craniotomy appears to be more advantageous for providing symptom relief in those with pre-operative symptoms.

Cytomegalovirus encephalitis in a hemodialysis patient: a rare association.

Haemodialysis patients are at greater risk of infections than individuals not on dialysis due to their immunosuppressive state caused by several factors (uraemia, vascular access, inflammation, malnutrition). However, infections affecting the central nervous system are not frequent in this population. We present the case of a 77-year-old man with end-stage renal disease who was admitted to the emergency department for a decreased level of consciousness and fever. Although the initial clinical suspicion oriented to a urinary infection, the lack of improvement forced us to perform a lumbar puncture. Five days after cerebrospinal fluid was cultured, cytomegalovirus was isolated and ganciclovir initiated.

Left Atrial Strain Predicts Stroke Recurrence and Death in Patients With Cryptogenic Stroke.

Left atrial strain (LAS) has been widely studied as a predictor of atrial fibrillation (AF) after cryptogenic stroke (CS). However, the evidence about its prognostic role in terms of stroke recurrence and death in this setting remains scarce. A total of 92 consecutive patients with ischemic stroke or transient ischemic attack with ABCD2 scale ≥4 of unknown etiology were prospectively recruited. Echocardiography, including LAS was performed during admission. The primary outcome measure was the composite of stroke recurrence or death. The mean age was 77.5 ± 7.7, and 58% of patients were female. After a median follow up of 28 months, the primary outcome measure occurred in 15 patients (16%). The primary outcome was more frequent in patients with diabetes (53% vs 21%, p = 0.02), chronic kidney disease (33% vs 10%, p = 0.034), and a history of heart failure (13% vs 0%, p = 0.025). LAS reservoir (LASr) and LAS conduit (LAScd) were lower in patients developing the primary outcome (21% ± 7% vs 28.8% ± 11%, p = 0.017 and 7.7% ± 3.9% vs 13.7% ± 7%, p = 0.007, respectively). On multivariate analysis, LASr (hazard ratio 0.9, 95% confidence interval 0.85 to 0.99, p = 0.048) and diabetes (hazard ratio 3.3, 95% confidence interval 1.03 to 10.4, p = 0.045) were associated with stroke recurrence or all-cause death after CS. On the log-rank test (using the discriminatory cut-off value of LASr <23%), LASr (p = 0.009) was associated with higher risk of the primary outcome. In conclusion, lower values of the LAS reservoir were associated with a higher risk of stroke recurrence or death after CS. LAS may identify patients at higher risk of thromboembolism and stress conditions.

Designing Synthetic, Sulfated Glycosaminoglycan Mimetics That Are Orally Bioavailable and Exhibiting In Vivo Anticancer Activity.

Sulfated glycosaminoglycans (GAGs), or synthetic mimetics thereof, are not favorably viewed as orally bioavailable drugs owing to their high number of anionic sulfate groups. Devising an approach for oral delivery of such highly sulfated molecules would be very useful. This work presents the concept that conjugating cholesterol to synthetic sulfated GAG mimetics enables oral delivery. A focused library of sulfated GAG mimetics was synthesized and found to inhibit the growth of a colorectal cancer cell line under spheroid conditions with a wide range of potencies ( 0.8 to 46 µM). Specific analogues containing cholesterol, either alone or in combination with clinical utilized drugs, exhibited pronounced in vivo anticancer potential with intraperitoneal as well as oral administration, as assessed by ex vivo tertiary and quaternary spheroid growth, cancer stem cell (CSC) markers, and/or self-renewal factors. Overall, cholesterol derivatization of highly sulfated GAG mimetics affords an excellent approach for engineering oral activity.

Usefulness of Tissue Tracking by Cardiac Magnetic Resonance to Predict Events in Patients With Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HC) is the most common cardiovascular inherited disease, and it is associated with arrhythmic events, heart failure, and death. Strain analysis by tissue tracking (TT) techniques on cardiac magnetic resonance (CMR) is a novel noninvasive diagnostic tool. However, the usefulness of CMR-TT to identify patients with HC at risk of adverse outcomes remains unknown. CMR strain parameters by CMR-TT were prospectively measured in a cohort of 136 consecutive patients with HC. Clinical (death or readmission for heart failure) and arrhythmic (any ventricular tachycardia) events during follow-up were prospectively recorded. Global radial systolic strain rate and global radial diastolic strain rate showed the best area under the receiver operating characteristic curve (ROC curve) to predict adverse clinical events. On Cox multivariate regression models, a global radial systolic strain rate value <1.4/s and a global radial diastolic strain rate value ≥ -1.38/s were independently associated with clinical events at follow-up (adjusted hazard ratio 6.57, 95% confidence interval [CI] 2.01 to 21.49, p = 0.002; adjusted hazard ratio 5.96, 95% CI 1.79 to 19.89, p = 0.004, respectively). Regarding arrhythmic events, global radial peak strain <27% showed the best area under the ROC curve and remained independently associated with ventricular tachycardia after adjustment for confounders (odds ratio 7.33, 95% CI 1.07 to 50.41, p = 0.043). CMR strain parameters by TT predict clinical and arrhythmic events in patients with HC.

Advanced Echocardiography With Left Atrial Strain and Indexed Left Atrial Three-Dimensional Volume for Predicting Underlying Atrial Fibrillation After Cryptogenic Stroke.

Cryptogenic stroke (CS) represents 1/3 of ischemic strokes. Atrial fibrillation (AF) can be detected in up to 30% of CS. Therefore, there is a clinical need for predicting AF to guide the optimal secondary prevention strategy. The evidence about the role of advanced echocardiography, including left atrial 3-dimensional (3D) index volume and left atrial strain (LAS) techniques, to predict underlying AF in this setting is lacking. From April 2019 to November 2021, 78 consecutive patients with ischemic stroke or transient ischemic attack with ABCD2 scale ≥4 of unknown etiology were prospectively recruited. Echocardiography was performed during admission. All patients underwent 15 days of wearable Holter monitoring. The primary outcome measure was AF detection during follow-up. Twenty-two patients (28%) developed AF. Patients in the AF group were older (81 ± 6.3 vs 76.5 ± 7.8 years; p = 0.012). Left atrial (LA) diastolic indexed volume was higher in the AF group (37.2 ± 12.8 vs 29.7 ± 11 ml/m2 p = 0.01). Three-D LA indexed volume was also higher in patients with AF (41.4 ± 14 vs 32.2 ± 10 ml/m2 p = 0.009). LAS reservoir, LAS conduct, and LAS contraction (LASct) were significantly lower in patients with AF (19 ± 5.6 vs 32% ± 10.3%; 9 ± 4.5 vs 15 ± 7.6; 10 ± 5.3 vs 17 ± 6.4, respectively, all p <0.001). On multivariate analysis, LASct <13.5% and LA 3D indexed volume >44.5 ml/m2 were independent predictors of AF (odds ratio 10.9 [95% confidence interval 1.09 to 108.2], p = 0.042). In conclusion, LASct <13.5% and LA 3D indexed volume >44.5 ml/m2 are independent predictors of underlying AF in patients with CS. Our results show the usefulness of advanced echocardiography in this challenging clinical setting.

Influence of air pollutants on circulating inflammatory cells and microRNA expression in acute myocardial infarction.

Air pollutants increase the risk and mortality of myocardial infarction (MI). The aim of this study was to assess the inflammatory changes in circulating immune cells and microRNAs in MIs related to short-term exposure to air pollutants. We studied 192 patients with acute coronary syndromes and 57 controls with stable angina. For each patient, air pollution exposure in the 24-h before admission, was collected. All patients underwent systematic circulating inflammatory cell analyses. According to PM2.5 exposure, 31 patients were selected for microRNA analyses. STEMI patients exposed to PM2.5 showed a reduction of CD4+ regulatory T cells. Furthermore, in STEMI patients the exposure to PM2.5 was associated with an increase of miR-146a-5p and miR-423-3p. In STEMI and NSTEMI patients PM2.5 exposure was associated with an increase of miR-let-7f-5p. STEMI related to PM2.5 short-term exposure is associated with changes involving regulatory T cells, miR-146a-5p and miR-423-3p.

Efficacy of short-course colchicine treatment in hospitalized patients with moderate to severe COVID-19 pneumonia and hyperinflammation: a randomized clinical trial.

Some patients with COVID-19 pneumonia develop an associated cytokine storm syndrome that aggravates the pulmonary disease. These patients may benefit of anti-inflammatory treatment. The role of colchicine in hospitalized patients with COVID-19 pneumonia and established hyperinflammation remains unexplored. In a prospective, randomized controlled, observer-blinded endpoint, investigator-initiated trial, 240 hospitalized patients with COVID-19 pneumonia and established hyperinflammation were randomly allocated to receive oral colchicine or not. The primary efficacy outcome measure was a composite of non-invasive mechanical ventilation (CPAP or BiPAP), admission to the intensive care unit, invasive mechanical ventilation requirement or death. The composite primary outcome occurred in 19.3% of the total study population. The composite primary outcome was similar in the two arms (17% in colchicine group vs. 20.8% in the control group; p = 0.533) and the same applied to each of its individual components. Most patients received steroids (98%) and heparin (99%), with similar doses in both groups. In this trial, including adult patients with COVID-19 pneumonia and associated hyperinflammation, no clinical benefit was observed with short-course colchicine treatment beyond standard care regarding the combined outcome measurement of CPAP/BiPAP use, ICU admission, invasive mechanical ventilation or death (Funded by the Community of Madrid, EudraCT Number: 2020-001841-38; 26/04/2020).

CD69 expression on regulatory T cells protects from immune damage after myocardial infarction.

Increasing evidence has pointed to the important function of T cells in controlling immune homeostasis and pathogenesis after myocardial infarction (MI), although the underlying molecular mechanisms remain elusive. In this study, a broad analysis of immune markers in 283 patients revealed significant CD69 overexpression on Tregs after MI. Our results in mice showed that CD69 expression on Tregs increased survival after left anterior descending (LAD) coronary artery ligation. Cd69-/- mice developed strong IL-17+ γδT cell responses after ischemia that increased myocardial inflammation and, consequently, worsened cardiac function. CD69+ Tregs, by induction of AhR-dependent CD39 ectonucleotidase activity, induced apoptosis and decreased IL-17A production in γδT cells. Adoptive transfer of CD69+ Tregs into Cd69-/- mice after LAD ligation reduced IL-17+ γδT cell recruitment, thus increasing survival. Consistently, clinical data from 2 independent cohorts of patients indicated that increased CD69 expression in peripheral blood cells after acute MI was associated with a lower risk of rehospitalization for heart failure (HF) after 2.5 years of follow-up. This result remained significant after adjustment for age, sex, and traditional cardiac damage biomarkers. Our data highlight CD69 expression on Tregs as a potential prognostic factor and a therapeutic option to prevent HF after MI.

Coronary Plaque Erosion after Abemaciclib Treatment Onset: An Unknown Side Effect?

The current article describes a 72-year-old woman who suffered an acute myocardial infarction due to plaque erosion (PE) 2 weeks after abemaciclib treatment onset due to advanced breast cancer. Abemaciclib is a cyclin-dependent kinase 4 and 6 inhibitor that has recently demonstrated efficacy and safety in advanced breast cancer. Of major concern, however, reported thromboembolic rates in randomized clinical trials testing this drug range from 0.6 to 5%. To the best of our knowledge this is the first thrombotic coronary side effect ever reported. We suggest that a treatment that increases thromboembolic risk, such abemaciclib, may have triggered PE in our patient, 15 days after abemaciclib initiation. New molecules are promising in cancer treatment; however, care must be paid to their potential cardiotoxic effects.

Electrocardiographic biomarkers to predict atrial fibrillation in sinus rhythm electrocardiograms.

OBJECTIVE: Early prediction of atrial fibrillation (AF) development would improve patient outcomes. We propose a simple and cheap ECG based score to predict AF development. METHODS: A cohort of 16 316 patients was analysed. ECG measures provided by the computer-assisted ECG software were used to identify patients. A first group included patients in sinus rhythm who showed an ECG with AF at any time later (n=505). A second group included patients with all their ECGs in sinus rhythm (n=15 811). By using a training set (75% of the cohort) the initial sinus rhythm ECGs of both groups were analysed and a predictive risk score based on a multivariate logistic model was constructed. RESULTS: A multivariate regression model was constructed with 32 variables showing a predictive value characterised by an area under the curve (AUC) of 0.776 (95% CI: 0.738 to 0.814). The subsequent risk score included the following variables: age, duration of P-wave in aVF, V4 and V5; duration of T-wave in V3, mean QT interval adjusted for heart rate, transverse P-wave clockwise rotation, transverse P-wave terminal angle and transverse QRS complex terminal vector magnitude. Risk score values ranged from 0 (no risk) to 5 (high risk). The predictive validity of the score reached an AUC of 0.764 (95% CI: 0.722 to 0.806) with a global specificity of 61% and a sensitivity of 55%. CONCLUSIONS: The automatic assessment of ECG biomarkers from ECGs in sinus rhythm is able to predict the risk for AF providing a low-cost screening strategy for early detection of this pathology.

The Role of Cost-Effectiveness Analysis in Patient-Centered Cancer Care in the Era of Precision Medicine.

Over the last few decades, changes in diagnostic and treatment paradigms have greatly advanced cancer care and improved outcomes [...].

Association of CHA2DS2-VASc Score With Remodeling of Left Atrial Appendage Assessed by Cardiac Computed Tomography.

BACKGROUND: CHA2DS2-VASc score (congestive heart failure; hypertension; ages ≥ 74 years (2 points); diabetes; stroke, transient ischemic attack, or systemic embolism (2 points); vascular disease; ages 65 - 74 years; sex (female)) is a widely used clinical scale to estimate the risk of stroke in patients with non-valvular atrial fibrillation (AF). However, the relationship between the increase in CHA2DS2-VASc score and atrial remodeling remains unsettled. METHODS: Twenty-five consecutive patients undergoing cardiac computed tomography (CT) were recruited. The systolic and diastolic volumes of left atrium and left atrial appendage (LAA) were measured. Risk of stroke was estimated using the CHA2DS2-VASc score. The relationship of the CHA2DS2-VASc score with morphological and functional variables was analyzed by Pearson's correlation. RESULTS: A positive correlation was documented between the CHA2DS2-VASc score and systolic (r = 0.419, P = 0.037) and diastolic (r = 0.415, P = 0.039) LAA volumes. Atrial volumes and left atrial ejection fraction showed no significant correlations with CHA2DS2-VASc. CONCLUSIONS: This study shows, for the first time, a positive correlation between CHA2DS2-VASc score and LAA remodeling.

Spontaneous coronary artery dissection in old patients: clinical features, angiographic findings, management and outcome.

AIMS: Spontaneous coronary artery dissection (SCAD) is a relatively rare but well-known cause of acute coronary syndrome. Clinical features, angiographic findings, management and outcomes of SCAD in old patients (>65 years of age) remain unknown. METHODS AND RESULTS: The Spanish multicentre prospective SCAD registry (NCT03607981), included 318 consecutive patients with SCAD. Data were collected between June 2015 and April 2019. All angiograms were analysed in a centralized corelab. For the purposes of this study, patients were classified according to age in two groups <65 and ≥65 years old and in-hospital outcomes were analysed. Fifty-five patients (17%) were ≥65 years old (95% women). Older patients had more often hypertension (76% vs. 29%, P < 0.01) and dyslipidaemia (56% vs. 30%, P < 0.01), and less previous (4% vs. 18%, P < 0.001) or current smoking habit (4% vs. 33%, P < 0.001). An identifiable trigger was less often present in old patients (27% vs. 43%, P = 0.028). They also had more often severe coronary tortuosity (36% vs. 11%, P = 0.036) and showed more frequently coronary ectasia (24% vs. 9%, P < 0.01). Older patients were more often managed conservatively (89% vs. 75%, P = 0.025), with no significant differences in major adverse cardiac events during index admission (7% vs. 8%, P = 0.858). There were no differences between groups in terms of in-hospital stay, new acute myocardial infarction, unplanned coronary angiography or heart failure. CONCLUSION: Older patients with SCAD show different clinical and angiographic characteristics compared with younger patients. Initial treatment strategy was different between groups, though in-hospital outcomes do not significantly differ (NCT03607981).