Outcomes of mitral TEER in non-responders to cardiac resynchronization therapy: A systematic review and Meta-analysis.

BACKGROUND: Secondary mitral regurgitation (MR) worsens in 10-15 % of heart failure (HF) patients receiving cardiac resynchronization therapy (CRT). Transcatheter edge-to-edge repair (TEER) with Mitra-Clip (Abbot Vascular, Santa Clara, CA, USA) therapy is associated with improved survival and decreased rates of hospitalization for HF in selected patients with secondary MR. Data on TEER outcomes in CRT-non-responders are limited. The purpose of this meta-analysis was to evaluate outcomes of mitral TEER with Mitra-Clip in CRT-non-responders. METHODS: Cochrane, Scopus, MEDLINE, and EMBASE were searched for studies discussing outcomes of Mitra-Clip in CRT non-responders. Two reviewers were independently involved in screening studies and extracting relevant data. Individual study incidence rate estimates underwent logit transformation to calculate the weighted summary proportion under the random effect model. RESULTS: A total of eight reports met the inclusion criteria (439 patients). Mitra-Clip improved MR grade to ≤2+ in 83.8 % and 86.8 % of CRT non-responders at six months and one year, respectively. Symptomatic improvement (New York Heart Association class ≤II) was also found in 71 % and 78.1 % of CRT non-responders at six months and one year, respectively. The pooled overall incidence estimates of mortality at 30 days, 6 months, 1 year, and 2 years were 3.6 %, 9.2 %, 17.8 %, and 25.9 %, respectively. CONCLUSION: TEER with Mitra-Clip in patients with significant secondary MR who do not respond to CRT was associated with MR improvement, alleviation of symptoms, and mortality rates similar to those in the COAPT trial.

Intravenous iron therapy for patients with iron deficiency and heart failure: a systematic review and meta-analysis of randomized controlled trials.

Introduction: Heart failure (HF) presents a significant health challenge, with intravenous (IV) iron therapy considered a potential treatment avenue. Method: We assessed IV iron therapy's efficacy in HF patients with concurrent iron deficiency versus standard of care. Primary outcomes included the composite of HF hospitalizations or cardiovascular-related mortality, HF hospitalizations, and all-cause, HF, and cardiovascular mortality rates. Secondary measures encompassed improvements in New York Heart Association functional classification, quality of life, 6-minute walk test, left ventricular ejection fraction, and adverse events. We used a random-effects model to compute relative risk (RR) or mean difference (MD) with 95% confidence intervals (CIs). Results: Based on an analysis of 14 randomized controlled trials involving 6614 patients, IV iron therapy significantly reduced composite outcome (RR: 0.84, 95% CI: 0.73, 0.96; P = 0.01) and HF hospitalizations (RR: 0.74, 95% CI: 0.61, 0.89; P = 0.002) compared to standard of care. Mortality rates showed no significant difference. IV iron therapy improved New York Heart Association functional classification, quality of life, and 6-minute walk test, with no major impact on left ventricular ejection fraction. Adverse events remained stable. Conclusions: IV iron therapy holds promise for diminishing HF hospitalizations and enhancing quality of life and 6-minute walk test in HF patients. Yet, its effect on all-cause or cardiovascular mortalities appears limited.

Cerebral embolic protection device utilization and outcomes in transcatheter aortic valve replacement: A nationally representative propensity matched analysis.

INTRODUCTION: In patients undergoing transcatheter aortic valve replacement (TAVR), cerebral embolic protection devices (CEPD) are used to possibly diminish the risk of periprocedural stroke. Trends and outcomes of CEPD usage in TAVR are not well characterized. METHODS: National readmission databases (NRD) 2017-2019 was used to identify hospital admissions for TAVR using ICD-10 codes, with versus without Sentinel CEPD. Primary outcomes of the study were in-hospital and 30-day stroke. Secondary outcomes include in-hospital mortality, 30-day mortality, 30-day readmission rate, and other procedural complications. We matched both cohorts using propensity score matching (PSM) and performed logistic regression to compute the odds ratios (ORs) and corresponding 95 % confidence intervals (CI). RESULTS: Out of 190,837 TAVR admissions in the United States, 10,643 (5.6 %) patients had TAVR with Sentinel CEPD. After propensity score matching, our cohort included 10,503 patients with CEPD and 10,541 without CEPD. Trends in CEPD utilization are noted in Fig. 1. In the PSM cohort, Sentinel CEPD was not associated with decreased risk of in-hospital stroke (1.9 % vs. 1.8 %, OR: 0.98, 95 % CI: 0.76-1.26, p = 0.88), 30-day stroke (2.1 % vs. 2.1 %, OR: 1.01, 95 % CI: 0.78-1.30, p = 0.96), or 30-day mortality (1.3 % vs. 1.0 %, OR: 0.74, 95 % CI: 0.51-1.07, p = 0.11) when compared to TAVR without CEPD. Other in-hospital and short-term outcomes post-TAVR were not impacted by Sentinel CEPD usage, including acute kidney injury, vascular complications, paravalvular leak, cardiogenic shock, circulatory support, or permanent pacemaker (Table 1). CONCLUSION: In this nationally representative cohort, Sentinel CEPD utilization during transfemoral TAVR for stroke prevention was not associated with reduced odds of in-hospital stroke, 30-day stroke, or 30-day mortality. Future studies should focus on optimizing patient selection for CEPD and establishing predictive models to identify the subset of TAVR patients with higher risk for periprocedural stroke who might benefit from CEPD.

Burden of cardiovascular disease in Sub-Saharan Africa, 1990-2019: An analysis of the Global Burden of Disease Study.

INTRODUCTION: The rise in cardiovascular disease (CVD) in Sub-Saharan Africa (SSA) reflects a major shift from communicable to noncommunicable diseases as primary health challenges. Consequently, this study aims to explore the burden of CVD and associated risk factors in SSA using data from the Global Burden of Disease (GBD) database. METHODS: This study utilized data from the GBD 1990 to 2019 to examine CVD prevalence in 46 SSA countries. We employed Bayesian regression models, demographic techniques, and mortality-to-incidence ratios to analyze both prevalence and mortality rates. Additionally, disability-adjusted life years (DALYs) were computed, and various risk factors were examined using the GBD's comparative risk assessment framework. RESULTS: Between 1990 and 2019, CVD raw counts in SSA rose by 131.7 %, with a 2.1 % increase in age-standardized prevalence rates. The most prevalent conditions were ischemic heart disease, stroke, and rheumatic heart disease. During the same period, the age-standardized CVD deaths per 100,000 individuals decreased from 314 (1990) to 269 (2019), reflecting a -14.4 % decline. Age-standardized CVD DALY rates also showed a decrease from 6,755 in 1990 to 5,476 in 2019, with translates to 18.9 % reduction. By 2019, the Central African Republic, Madagascar, and Lesotho were the countries with the highest age-standardized DALY rates for all CVDs. CONCLUSIONS: The study highlights a contrasting trend in SSA's CVD landscape: a decrease in age-standardized mortality and DALYs contrasts with increasing CVD prevalence, emphasizing the need for targeted public health strategies that balance treatment advancements with intensified prevention and control measures.

Liberal versus conservative transfusion strategy for patients with acute myocardial infarction and anemia: A systematic review and meta-analysis.

BACKGROUND: A hemoglobin (Hb) level goal of 7-8 g/dL is a standard care threshold, prompting blood transfusion. The debate over whether acute myocardial infarction (MI) patients benefit from a more liberal transfusion strategy prompted a meta-analysis of relevant trials. METHODS: We performed a meta-analysis of randomized controlled trials (RCTs) comparing liberal and restrictive transfusion strategies in anemic MI patients. Primary outcomes were recurrent MI and death/MI, while secondary outcomes included stroke, revascularization, heart failure, and all-cause mortality. Due to the limited trials, we utilized the Paul-Mendele method with Hartung Knapp adjustment. RESULTS: Involving 2155 patients with liberal transfusion and 2170 with conservative transfusion across four RCTs, liberal transfusion did not significantly reduce MI (relative risk [RR] 0.85; 95 % CI 0.72 - 1.02, p = 0.07) or death/MI (RR 0.88; 95 % CI 0.45 - 1.71, p = 0.57). No significant differences were observed in all-cause mortality (RR 0.82; 95 % CI 0.25 - 2.68, p = 0.63), stroke (RR 0.89; 95 % CI 0.48 - 1.64, p = 0.50), revascularization (RR 0.93; 95 % CI 0.48 - 1.80, p = 0.68), or heart failure (RR 1.14; 95 % CI 0.04 - 28.84, p = 0.88). CONCLUSION: Our meta-analysis supports current medical guidelines, reinforcing the practice of limiting transfusions in acute MI patients to those with an Hb level of 7 or 8 g/dL. Liberal transfusion strategies did not show improved clinical outcomes.

Bivalirudin versus unfractionated heparin in patients with myocardial infarction undergoing percutaneous coronary intervention: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Bivalirudin is an alternative accepted therapy to unfractionated heparin for patients with myocardial infarction (MI) undergoing percutaneous coronary intervention (PCI). We aimed in this meta-analysis to compare bivalirudin versus unfractionated heparin in patients with MI undergoing PCI. METHODS: We have screened PubMed/MEDLINE, Cochrane Library, and ClinicalTrials.gov (inception through January 8th, 2023) for randomized controlled trials (RCTs) evaluating bivalirudin versus unfractionated heparin in patients with MI undergoing PCI. The DerSimonian and Laird method was used for estimation of tau2 to calculate the risk ratio (RR) and 95 % confidence interval (CI). RESULTS: Ten RCTs with a total of 40,069 participants were included in our analysis. Bivalirudin as compared with unfractionated heparin was associated with significant decrease in major bleeding (RR 0.64 [0.52 to 0.79]; p < 0.01; I2 = 69 %) and cardiovascular mortality (RR 0.79 [0.67 to 0.92]; p < 0.01; I2 = 0 %). There was no significant difference between bivalirudin and unfractionated heparin groups in terms of major adverse cardiovascular events (RR 1.02 [0.91 to 1.14]; p = 0.73; I2 = 52 %), all-cause mortality (RR 0.89 [0.77 to 1.04]; p = 0.15; I2 = 23 %), MI (RR 1.02 [0.87 to 1.19]; p = 0.80; I2 = 36 %), stent thrombosis (RR 1.12 [0.52 to 2.40]; p = 0.77; I2 = 82 %), or stroke (RR 0.97 [0.73 to 1.29]; p = 0.85; I2 = 0 %). CONCLUSION: Our meta-analysis suggests that bivalirudin compared with unfractionated heparin in patients with MI undergoing PCI was associated with lower rates of major bleeding and cardiovascular mortality without a significant difference in major adverse cardiovascular events, all-cause mortality, MI, stroke, or stent thrombosis.

Sex Differences in the Clinical Outcomes of Patients With Takotsubo Stress Cardiomyopathy: A Meta-Analysis of Observational Studies.

The incidence of takotsubo stress cardiomyopathy (TSCM) in males is low compared with females. Gender-based differences in clinical outcomes of TSCM are not well characterized. The aim of this meta-analysis was to analyze whether gender-based differences are observed in TSCM clinical outcomes. A comprehensive literature search of PubMed, Embase, Cochrane Library database, and Web of Science was performed from inception to June 20, 2022, for studies comparing the clinical outcomes between male and female patients with TSCM. The primary outcome of interest was in-hospital all-cause mortality and cardiogenic shock. The secondary outcomes were cardiovascular mortality, receipt of mechanical ventilation, intra-aortic balloon pump, occurrence of ventricular arrhythmia, and left ventricular thrombus. A random-effects model was used to calculate the risk ratios (RR) and confidence intervals (CI). Heterogenicity was assessed using the Higgins I2 index. Twelve observational studies involving 51,213 patients (4,869 males and 46,344 females) were included in the meta-analysis. Male gender was associated with statistically significant higher in-hospital all-cause mortality compared with females in patients with TSCM (RR 2.17, 95% CI 1.77 to 2.67, p <0.001). The rate of cardiogenic shock was significantly higher in males with TSCM compared with females (RR 1.66, 95% CI 1.29 to 2.12, p <0.001). Our meta-analysis showed a difference in the clinical outcomes of TSCM between men and women. Male gender was associated with a two-fold greater in-hospital all-cause mortality risk compared with female gender. The higher mortality risk associated with male gender deserves further study, particularly whether it represents later recognition of the condition and disparities in treatments.

Meta-Analysis of the Outcomes of Peri-Device Leak After Left Atrial Appendage Closure.

Left atrial appendage closure (LAAC) reduces the risk of thromboembolic stroke in atrial fibrillation. Peri-device leak (PDL) after LAAC may affect the subsequent risk of thromboembolism. We conducted a systematic review and meta-analysis to evaluate the effect of PDL after LAAC. We searched PubMed/Medline, Embase, and Google Scholar for studies reporting outcomes of PDL after LAAC from inception through October 2022. The primary outcome was the composite of stroke, transient ischemic attack (TIA), or systemic embolism (SE). Secondary outcomes included all-cause and cardiovascular mortality, ischemic stroke, TIA, and device-related thrombus. Outcomes were pooled using random-effects models. We used I2 statistics to assess statistical heterogeneity; I2 >50% considered significant heterogeneity. This study included 54,279 patients from 11 studies (6 observational, 2 nonrandomized controlled trials [non-RCTs] primary results, 2 RCT post hoc analyses, and 1 analysis combining 2 RCTs data). PDL was associated with a significant increase in the composite outcome of stroke, TIA, or SE (odds ratio 1.63, 95% confidence interval 1.06 to 2.52, p = 0.03, I2 = 43%) as compared with cases with no PDL. There were no significant differences in all-cause or cardiovascular mortality, ischemic stroke, TIA, or device-related thrombus. In conclusion, PDL after LAAC is associated with an increased risk of thromboembolism (composite stroke, TIA, or SE) without impacting mortality.

Hypothermia as an Adjunctive Therapy in Cardiogenic Shock: A Systematic Review and Meta-Analysis.

In the setting of out-of-hospital cardiac arrest, therapeutic hypothermia (TH) has been shown to improve clinical outcomes. However, trials showing the advantage of TH did not include patients with cardiogenic shock (CS). We performed a comprehensive literature search for studies that evaluated the efficacy and safety of adjunctive TH compared with the standard of care (SOC) in patients with CS. The primary outcome was the mortality rate (in-hospital, short-, and mid-term). The secondary outcomes were the TH-related complications, duration of Intensive Care Unit (ICU) stay, duration of mechanical ventilation (MV-days), and improvement in cardiac function. Relative risk (RR) or the standardized mean difference (SMD) and corresponding 95% confidence intervals (CIs) were calculated using the random-effects model. A total of 7 clinical studies (3 RCTs included), and 712 patients (341 in the TH group and 371 in the SOC group) were included. As compared with the SOC, TH was not associated with a statistically significant improvement in the in-hospital (RR: 0.73%, 95% CI: 0.51-1.03; p = 0.08), short-term (RR: 0.90%, 95% CI: 0.75-1.06; p = 0.21), or mid-term (RR: 0.93%, 95% CI: 0.78-1.10; p = 0.38) mortality rates. Despite the improvement in the cardiac function in the TH group (SMD: 1.08, 95% CI: 0.02-2.1; p = 0.04), the TH strategy did not significantly shorten the MV days, or the ICU stay (p-values >0.05). Finally, there was a trend toward higher risks for infection, major bleeding, and the need for blood transfusion in the TH group. According to our meta-analysis of published clinical studies, TH is not beneficial in patients with CS and has a marginal safety profile. Larger-scale RCTs are needed to further clarify our results.

Cognitive behavioral therapy for depression in patients with heart failure: a systematic review and metanalysis of randomized control trials.

Major depression (MD) is prevalent in patients with heart failure (HF) and contributes to increased risk of hospitalization and mortality. The implementation of cognitive behavioral therapy (CBT) has become a key strategy for treating HF patients' depression. We performed a comprehensive literature search for studies that evaluated the efficacy of adjunctive CBT compared to the standard of care (SOC) in HF patients with MD. The primary outcome was the depression scale (post-intervention and by the end of follow-up). The secondary outcomes were the quality of life (QoL), self-care scores, and 6-min walk test distance(6-MW). The standardized mean difference (SMD) and corresponding 95% confidence intervals (CIs) were calculated using the random-effects model. A total of 6 RCTs with 489 patients (244 in the CBT group and 245 in the SOC group) were included. As compared to the SOC, CBT was associated with a statistically significant improvement in the post-interventional depression scale (SMD: -0.45, 95%CI: -0.69, -0.21; P < 0.01) and by the end of follow-up (SMD: -0.68, 95%CI: -0.87, -0.49; P < 0.01). Furthermore, CBT significantly improved the QoL (SMD: -0.45, 95%CI: -0.65, -0.24; P < 0.01). However, there were no differences in the self-care scores (SMD: 0.17, 95%CI: -0.08, 0.42; P = 0.18) or in 6-MW (SMD: 0.45, 95%CI: -0.39, 1.28; P = 0.29) between the two groups. According to our meta-analysis of published clinical studies, CBT may be more effective than standard therapy at enhancing depression scores and quality of life. To assess the long-term clinical effects of CBT in heart failure patients, larger and more powerful RCTs are required.

Traditional versus distal radial access for coronary angiography: a meta-analysis of randomized controlled trials.

Radial artery occlusion (RAO) is a well known complication that occurs after traditional radial artery (TRA) intervention and limits the radial artery as a future access site, as well as an arterial conduit. Distal radial artery (DRA) access has emerged recently as an alternative approach with a potential lower incidence of RAO. Database search of Pubmed/MEDLINE, Cochrane Library, and EMBASE was conducted by two authors from inception through 1 October 2022. Randomized trials that compared TRA with the DRA approach to perform coronary angiography were included. Two authors extracted pertinent data into predefined data collection tables. The risk ratios and 95% confidence intervals (CIs) were reported. Eleven trials were included (5700 patients) in the study. The mean age was 62.0 ±â€…10.9 years. Compared with DRA, vascular access through the TRA was associated with a higher incidence of RAO (risk ratio 3.05, 95% CI, 1.74-5.35, P < 0.01); however, arterial access by using the TRA was associated with a lower incidence of access failure leading to a crossover compared with the DRA approach (risk ratio 0.35; 95% CI, 0.21-0.57, P < 0.01). The incidence of radial artery spasm and access site-associated hematoma was not significant in the group treated with TRA compared with the DRA approach (P > 0.05). The DRA approach was associated with a lower incidence of RAO compared with the TRA approach but this was at the expense of a higher crossover rate.

The Contemporary Use of Intracoronary Brachytherapy for In-Stent Restenosis: A Review.

In-stent restenosis (ISR) has been a major limitation in interventional cardiology and constitutes nearly 10 % of all percutaneous coronary interventions in the United States. Drug-eluting stent (DES) restenosis proves particularly difficult to manage and poses a high risk of recurrence and repeat intervention. Intra-coronary brachytherapy (IBT) has been traditionally viewed as a potential treatment modality for ISR. However, its use was hindered by procedural complexity, cost, and the advent of newer-generation DES. Recent data suggests promising results regarding IBT for the treatment of resistant DES-ISR. This review addresses the mechanism of action of IBT, procedural details, and associated risks and complications of its use. It will also highlight the available clinical evidence supporting the use of IBT and the future directions of its utilization in the treatment of ISR.

The Evolving Trends in Infective Endocarditis and Determinants of Mortality: a 10-year Experience From a Tertiary Care Epicenter.

The epidemiology of infective endocarditis (IE) continues to evolve in areas affected by the opioid epidemic. Understanding the demographics of the disease allows us to better tailor therapy towards this at-risk population. This was an observational study of adults (age ≥ 18) admitted to the University of Kentucky hospital with IE between January 2009 and December 2018. 1,255 patients were included in the final analysis. The mean age was 42 years, 45% were female and injection drug use was seen in 66% of patients. On multivariable analysis, higher Charlson comorbidity indices, left sided, and multivalve involvement were associated with increased mortality, whereas surgical intervention demonstrated a trend towards lower mortality. Our results highlight the alarming increase in injection drug use related IE and the high mortality rates despite therapeutic advances. Patients with left sided IE, multivalve involvement and a higher Charlson comorbidity index had decreased survival.

Pregnancy and Fetal Outcomes in Patients With Ehlers-Danlos Syndrome: A Nationally Representative Analysis.

Cardiovascular complications occur frequently in Ehlers-Danlos syndrome (EDS). Pregnancy outcomes, however, are not well established in patients with EDS. We conducted a population-based, retrospective, cohort study using the national inpatient sample to compare pregnancy and fetal outcomes in patients with and without EDS, delivering between 2016 and 2019. Regression analysis was performed and adjusted for maternal age and race to compare both groups. Of the total 5,887,050 births in our cohort, 1016 were to patients with EDS. The EDS cohort was more likely to be older, white and have multiple comorbidities, such as smoking, mitral valve prolapse, and chronic hypertension. When we adjusted for age and race, patients with EDS were more likely than those without EDS to require Cesarean-section, develop postpartum hemorrhage, experience intrauterine growth restriction, and deliver preterm. In this study, patients with EDS experienced higher rates of maternal complications, however, aortic aneurysmal rupture was not among them.

Long-Term Surveillance of Coronary Artery Dissection in an Orthotopic Heart Transplant Recipient.

We describe a case of an orthotopic heart transplant recipient who presented with chest pain related to blunt chest trauma 3 weeks post-transplantation. Electrocardiogram showed anterior ST-segment elevation. Coronary angiography revealed a dissection of the mid-distal left anterior descending artery with preserved antegrade flow. Conservative management of the coronary artery dissection was pursued. While the patient had a favorable long-term clinical outcome, the coronary dissection persisted on 1- and 2-year follow-up coronary angiography.

Independent Risk Factors for Thromboembolic Events in High-Risk Patients With Takotsubo Cardiomyopathy.

Takotsubo cardiomyopathy (TCM) is characteristically associated with left ventricular apical ballooning and regional wall motion abnormalities that predispose to the formation of left ventricular (LV) thrombi and subsequent thromboembolic events (VTE). There is limited data about the risk factors of developing stroke in the absence of LV thrombi in patients with TCM. Identify risk factors that predispose patients with TCM to develop VTE and stroke. We retrospectively reviewed all patients admitted with a primary diagnosis of stress induced or Takotsubo cardiomyopathy at a large tertiary care center from 2005 to 2019. Patients who met the echocardiographic criteria of TCM, had resolution of WMA on repeat echocardiogram, did not have coronary artery disease if angiography was performed and survived for > 3 months after index presentation were included in the analysis. Patients were followed for up to a period of 1 year. Multivariate analysis was performed to identify predictors of thromboembolism. Among the 400 patients who presented with TCM, 146 patients were included in the analysis. A total of 13 patients (8.9%) had documented thromboembolic events. Patients with VTE more often had Atrial fibrillation (30.8% vs 6.8%, P = 0.018), higher LV mass (224.5g vs 184g, P = 0.04), lower EF on presentation (31.5% vs 40%, P = 0.011) and were less likely to have undergone coronary angiography following diagnosis (23.1% vs 54.9%, P = 0.04). On multivariate analysis, atrial fibrillation (OR 9.15, CI 1.15-72.70) and low ejection fraction on admission (OR 0.88, CI 0.81-0.97) were independent risk factors for the development of VTE. Atrial fibrillation and low ejection fraction on presentation were associated with higher risk of developing thromboembolic events in patients with TCM.

Hypothermia as an Adjunctive Therapy to Percutaneous Intervention in ST-Elevation Myocardial Infarction: A Systematic Review and Meta-Analysis of Randomized Control Trials.

INTRODUCTION: In the setting of acute ST-elevation myocardial infarction (STEMI), several randomized control trials (RCTs) suggested a potential benefit with the use of therapeutic hypothermia (TH). However, results from previous studies are contradictory. METHOD: We performed a comprehensive literature search for studies that evaluated the efficacy and safety of adjunctive TH compared to the standard percutaneous coronary intervention (PCI) in awake patients with STEMI. The primary outcomes were the infarct size (IS) and microvascular obstruction (MVO) assessed by cardiac imaging at the end of follow-up. The secondary outcomes were major adverse cardiovascular events (MACE), procedure-related complications, and door-to-balloon time. Relative risk (RR) or the mean difference (MD) and corresponding 95 % confidence intervals (CIs) were calculated using the random-effects model. RESULTS: A total of 10 RCTs, including 706 patients were included. As compared to standard PCI, TH was not associated with a statistically significant improvement in the IS (MD: -0.87 %, 95%CI: -2.97, 1.23; P = 0.42) or in the MVO (MD: 0.11 %, 95%CI: -0.06, 0.27; P = 0.21). MACE and its components were comparable between the two groups. However, the TH approach was associated with an increased risk of infection and prolonged door-to-balloon time. Furthermore, there was a trend in the TH group toward an increased incidence of stent thrombosis and paroxysmal atrial fibrillation. CONCLUSIONS: According to our meta-analysis of published RCTs, TH is not beneficial in awake patients with STEMI and has a marginal safety profile with potential for care delays. Larger-scale RCTs are needed to further clarify our results.