SGLT2 Inhibitors, Functional Capacity, and Quality of Life in Patients With Heart Failure: A Systematic Review and Meta-Analysis.

Importance: The associations of sodium glucose cotransporter-2 inhibitors (SGLT2is) with reduction in mortality and hospitalization rates in patients with heart failure (HF) are well established. However, their association with improving functional capacity and quality of life (QOL) has been variably studied and less reported. Objective: To provide evidence on the extent to which SGLT2is are associated with improvement on objective measures of functional capacity and QOL in patients living with HF. Data Sources: The MEDLINE, EMBASE, and Cochrane databases were systematically searched for relevant articles on July 31, 2023. Study Selection: Randomized, placebo-controlled clinical trials reporting the effect of SGLT2i on functional outcomes of exercise capacity (peak oxygen consumption [peak VO2] or 6-minute walk distance [6MWD]) and/or QOL using validated questionnaires for patients with HF were included. Data Extraction and Synthesis: Data were extracted by 2 authors following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, and a meta-analysis using the restricted maximum likelihood random-effects model was conducted. Main Outcomes and Measures: Outcomes of interest included changes in peak VO2, 6MWD, and Kansas City Cardiomyopathy Questionnaire-12 total symptom score (KCCQ-TSS), clinical summary score (KCCQ-CSS), and overall summary score (KCCQ-OSS). Results: In this meta-analysis of 17 studies, 23 523 patients (mean [range] age, 69 [60-75] years) were followed over a period ranging from 12 to 52 weeks. Four studies included peak VO2 as an outcome, 7 studies included 6MWD, and 10 studies reported KCCQ scores. Mean (SD) left ventricular ejection fraction was 43.5% (12.4%). Compared with controls, patients receiving SGLT2i treatment experienced significant increases in peak VO2 (mean difference [MD], 1.61 mL/kg/min; 95% CI, 0.59-2.63 mL/kg/min; P = .002) and 6MWD (MD, 13.09 m; 95% CI, 1.20-24.97 m; P = .03). SGLT2i use was associated with increased KCCQ-TSS (MD, 2.28 points; 95% CI, 1.74-2.81 points; P < .001), KCCQ-CSS (MD, 2.14 points; 95% CI, 1.53-2.74 points; P < .001), and KCCQ-OSS (MD, 1.90 points; 95% CI, 1.41-2.39 points; P < .001) scores. Subgroup analysis and meta-regression demonstrated almost all improvements were consistent across ejection fraction, sex, and the presence of diabetes. Conclusions and Relevance: These findings suggest that in addition to known clinical associations with mortality and hospitalization outcomes, SGLT2i use is associated with improvement in outcomes of interest to patients' everyday lives as measured by objective assessments of maximal exercise capacity and validated QOL questionnaires, regardless of sex or ejection fraction.

Role of Cerebral Embolic Protection Devices in Patients Undergoing Transcatheter Aortic Valve Replacement: An Updated Meta-Analysis.

BACKGROUND: Cerebral embolic protection devices (CEPD) capture embolic material in an attempt to reduce ischemic brain injury during transcatheter aortic valve replacement. Prior reports have indicated mixed results regarding the benefits of these devices. With new data emerging, we performed an updated meta-analysis examining the effect of CEPD during transcatheter aortic valve replacement on various clinical, neurological, and safety parameters. METHODS AND RESULTS: A comprehensive review of electronic databases was performed comparing CEPD and no-CEPD in transcatheter aortic valve replacement. Primary clinical outcome was all-cause stroke. Secondary clinical outcomes were disabling stroke and all-cause mortality. Neurological outcomes included worsening of the National Institutes of Health Stroke Scale score, Montreal Cognitive Assessment score from baseline at discharge, presence of new ischemic lesions, and total lesion volume on neuroimaging. Safety outcomes included major or minor vascular complications and stage 2 or 3 acute kidney injury. Seven randomized controlled trials with 4016 patients met the inclusion criteria. There was no statistically significant difference in the primary clinical outcome of all-cause stroke; secondary clinical outcomes of disabling stroke, all-cause mortality, neurological outcomes of National Institutes of Health Stroke Scale score worsening, Montreal Cognitive Assessment worsening, presence of new ischemic lesions, or total lesion volume on diffusion-weighted magnetic resonance imaging between CEPD versus control groups. There was no statistically significant difference in major or minor vascular complications or stage 2 or 3 acute kidney injury between the groups. CONCLUSIONS: The use of CEPD in transcatheter aortic valve replacement was not associated with a statistically significant reduction in the risk of clinical, neurological, and safety outcomes.

Clinical outcomes of intravenous iron therapy in patients with heart failure and iron deficiency: Meta-analysis and trial sequential analysis of randomized clinical trials.

BACKGROUND: Iron deficiency in patients with heart failure (HF) is underdiagnosed and undertreated. The role of intravenous (IV) iron is well-established to improve quality of life measures. Emerging evidence also supports its role in preventing cardiovascular events in patients with HF. METHODOLOGY: We conducted a literature search of multiple electronic databases. Randomized controlled trials that compared IV iron to usual care among patients with HF and reported cardiovascular (CV) outcomes were included. Primary outcome was the composite of first heart failure hospitalization (HFH) or CV death. Secondary outcomes included HFH (first or recurrent), CV death, all-cause mortality, hospitalization for any cause, gastrointestinal (GI) side effects, or any infection. We performed trial sequential and cumulative meta-analyses to evaluate the effect of IV iron on the primary endpoint, and on HFH. RESULTS: Nine trials enrolling 3337 patients were included. Adding IV iron to usual care significantly reduced the risk of first HFH or CV death [risk ratio (RR) 0.84; 95 % confidence interval (CI) 0.75-0.93; I2 = 0 %; number needed to treat (NNT) 18], which was primarily driven by a reduction in the risk of HFH of 25 %. IV iron also reduced the risk of the composite of hospitalization for any cause or death (RR 0.92; 95 % CI 0.85-0.99; I2 = 0 %; NNT 19). There was no significant difference in the risk of CV death, all-cause mortality, adverse GI events, or any infection among patients receiving IV iron compared to usual care. The observed benefits of IV iron were directionally consistent across trials and crossed both the statistical and trial sequential boundaries of benefit. CONCLUSION: In patients with HF and iron deficiency, the addition of IV iron to usual care reduces the risk of HFH without affecting the risk of CV or all-cause mortality.

Isovolumic Contraction Velocity in Heart Failure With Reduced Ejection Fraction and Effect of Sacubitril/Valsartan: the PROVE-HF Study.

OBJECTIVES: To assess tissue Doppler-derived mitral annular isovolumic contraction velocity (ICV) after starting sacubitril/valsartan (sac/val) for the treatment of heart failure with reduced ejection fraction (HFrEF) and left ventricular [LV] EF < 40%). BACKGROUND: ICV may inform load-independent systolic function; combining ICV and LVEF may improve assessment of LV contractility. METHODS: Among 651 participants with HFrEF treated with sac/val, echocardiograms were performed at baseline, 6 and 12 months. Pretreatment median ICVs and LVEFs were used for classification to predict LV reverse remodeling, health status using the Kansas City Cardiomyopathy Questionnaire, and biomarker concentrations. RESULTS: The mean age was 64.6 ± 12.4 years, and 28% were women, baseline LVEF: 28.9% ± 6.9%. Compared to baseline, median ICV increased post sac/val therapy (4.6 [3.5, 6.1] vs 4.9 [3.6, 6.4]; P = 0.005). ICV added value to separate and combined models of biomarkers and clinical and echocardiographic variables for prediction of post-therapy EF recovery. Classification using baseline ICV/EF yielded relatively equal numbers in 4 groups based on low/high ICV or LVEF. Most deleterious results for remodeling, health status and biomarkers were found in patients with low ICV/low EF, whereas patients with high ICV/high EF had the best profiles; other groups were intermediate. Significant shifts toward better ICV/EF profiles were noted post sac/val treatment compared to baseline, with doubling of high ICV/high EF (241 [60%] vs 123 [31%]) and 78% reduction of low ICV/low EF (28 [7%] vs 125 [32%]). CONCLUSIONS: In HFrEF, ICV adds to the profiling of systolic function and represents an independent predictor of reverse cardiac remodeling after treatment with sac/val. ICV changes may be used for assessment of treatment responses.

Left Ventricular Unloading With Impella Versus IABP in Patients With VA-ECMO: A Systematic Review and Meta-Analysis.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) use for circulatory support in cardiogenic shock results in increased left ventricular (LV) afterload. The use of concomitant Impella or intra-aortic balloon pump (IABP) have been proposed as adjunct devices for LV unloading. The authors sought to compare head-to-head efficacy and safety outcomes between the 2 LV unloading strategies. We conducted a search of Medline, EMBASE, and Cochrane databases to identify studies comparing the use of Impella to IABP in patients on VA-ECMO. The primary outcome of interest was in-hospital mortality. The secondary outcomes included transition to durable LV assist devices/cardiac transplantation, stroke, limb ischemia, need for continuous renal replacement therapy, major bleeding, and hemolysis. Pooled risk ratios (RRs) with 95% confidence interval and heterogeneity statistic I2 were calculated using a random-effects model. A total of 7 observational studies with 698 patients were included. Patients on VA-ECMO unloaded with Impella vs IABP had similar risk of short-term all-cause mortality, defined as either 30-day or in-hospital mortality- 60.8% vs 64.9% (RR 0.93 [0.71 to 1.21], I2 = 71%). No significant difference was observed in transition to durable LV assist devices/cardiac transplantation, continuous renal replacement therapy initiation, stroke, or limb ischemia between the 2 strategies. However, the use of VA-ECMO with Impella was associated with increased risk of major bleeding (57.2% vs 39.7%) (RR 1.66 [1.12 to 2.44], I2 = 82%) and hemolysis (31% vs 7%) (RR 4.61 [1.24 to 17.17], I2 = 66%) compared with VA-ECMO, along with IABP. In conclusion, in patients requiring VA-ECMO for circulatory support, the concomitant use of Impella or IABP had comparable short-term mortality. However, Impella use was associated with increased risk of major bleeding and hemolysis.

Clinical Profiles, Outcomes, and Sex Differences of Patients With STEMI: Findings From the NORIN-STEMI Registry.

Background: Low- and middle-income countries account for most of the global burden of coronary artery disease. There is a paucity of data regarding epidemiology and outcomes for ST-segment elevation myocardial infarction (STEMI) patients in these regions. Objectives: The authors studied the contemporary characteristics, practice patterns, outcomes, and sex differences in patients with STEMI in India. Methods: NORIN-STEMI (North India ST-Segment Elevation Myocardial Infarction Registry) is an investigator-initiated prospective cohort study of patients presenting with STEMI at tertiary medical centers in North India. Results: Of 3,635 participants, 16% were female patients, one-third were <50 years of age, 53% had a history of smoking, 29% hypertension, and 24% diabetes. The median time from symptom onset to coronary angiography was 71 hours; the majority (93%) presented first to a non-percutaneous coronary intervention (PCI)-capable facility. Almost all received aspirin, statin, P2Y12 inhibitors, and heparin on presentation; 66% were treated with PCI (98% femoral access) and 13% received fibrinolytics. The left ventricular ejection fraction was <40% in 46% of patients. The 30-day and 1-year mortality rates were 9% and 11%, respectively. Compared with male patients, female patients were less likely to receive PCI (62% vs 73%; P < 0.0001) and had a more than 2-fold greater 1-year mortality (22% vs 9%; adjusted HR: 2.1; 95% CI: 1.7-2.7; P < 0.001). Conclusions: In this contemporary registry of patients with STEMI in India, female patients were less likely to receive PCI after STEMI and had a higher 1-year mortality compared with male patients. These findings have important public health implications, and further efforts are required to reduce these gaps.

Trends in Veno-Arterial Extracorporeal Life Support With and Without an Impella or Intra-Aortic Balloon Pump for Cardiogenic Shock.

Background Mechanical circulatory support devices, such as the intra-aortic balloon pump (IABP) and Impella, are often used in patients on veno-arterial extracorporeal life support (VA-ECLS) with cardiogenic shock despite limited supporting clinical trial data. Methods and Results Hospitalizations for cardiogenic shock from 2016 to 2018 were identified from the National Inpatient Sample. Trends in the use of VA-ECLS with and without an IABP or Impella were assessed semiannually. Multivariable logistic regression and general linear regression evaluated the association of Impella and IABP use with in-hospital outcomes. Overall, 12 035 hospitalizations with cardiogenic shock and VA-ECLS were identified, of which 3115 (26%) also received an IABP and 1880 (16%) an Impella. Use of an Impella with VA-ECLS substantially increased from 10% to 18% over this period (P<0.001), whereas an IABP modestly increased from 25% to 26% (P<0.001). In-hospital mortality decreased 54% to 48% for VA-ECLS only, 61% to 58% for VA-ECLS with an Impella, and 54% to 49% for VA-ECLS with an IABP (P<0.001 each). Most (57%) IABPs or Impellas were placed on the same day as VA-ECLS. After adjustment, there were no differences in in-hospital mortality or length of stay with the addition of an IABP or Impella compared with VA-ECLS alone. Conclusions From 2016 to 2018 in the United States, use of an Impella and IABP with VA-ECLS significantly increased. More than half of Impellas and IABPs were placed on the same day as VA-ECLS, and the use of a second mechanical circulatory support device did not impact in-hospital mortality. Further studies are needed to decipher the optimal timing and patient selection for this growing practice.

Coronary flow abnormalities in chronic kidney disease: A systematic review and meta-analysis.

BACKGROUND: Coronary vasomotion abnormalities have been described in small studies but not studied systematically. We aimed to review the present literature and analyze it to improve our understanding of chronic kidney disease (CKD) related-coronary microvascular dysfunction. OBJECTIVE: Coronary flow reserve (CFR) is a well-known measure of coronary vasomotion. We aimed to assess the difference in CFR among participants with and without CKD. METHODS: PubMed, Embase, and Cochrane CENTRAL were systematically reviewed to identify studies that compared CFR in participants with and without CKD. We estimated standardized mean differences in mean CFR reported in these studies. We performed subgroup analyses according to imaging modality, and the presence of significant epicardial coronary artery disease. RESULTS: In 14 observational studies with 5966 and 1410 patients with and without CKD, the mean estimated glomerular filtration rate (eGFR) was 29 ± 04 and 87 ± 25 ml/min/1.73 m2 , respectively. Mean CFR was consistently lower in patients with CKD in all studies and the cumulative mean difference was statistically significant (2.1 ± .3 vs. 2.7 ± .5, standardized mean difference -.8, 95% CI -1.1, -.6, p < .05). The lower mean CFR was driven by both significantly higher mean resting flow velocity (.58 cm/s, 95% CI .17, .98) and lower mean stress flow velocity (-.94 cm/s, 95% CI -1.75, -.13) in studies with CKD. This difference remained significant across diagnostic modalities and even in absence of epicardial coronary artery disease. In meta-regression, there was a significant positive relationship between mean eGFR and mean CFR (p < .05). CONCLUSION: Patients with CKD have a significantly lower CFR versus those without CKD, even in absence of epicardial coronary artery disease. There is a linear association between eGFR and CFR. Future studies are required to understand the mechanisms and therapeutic implications of these findings. KEY POINTS: In this meta-analysis of observational studies, there was a significant reduction in coronary flow reserve in studies with chronic kidney disease versus those without. This difference was seen even in absence of epicardial coronary artery disease. In meta-regression, a lower estimate glomerular filtration rate was a significant predictor of lower coronary flow reserve. Coronary microvascular dysfunction, rather than atherosclerosis-related epicardial disease may underly increase cardiovascular risk in a patient with chronic kidney disease.

Benefits of Adding Glucagon-Like Peptide 1 Receptor Agonists to Sodium-Glucose Co-Transporter 2 Inhibitors in Diabetic Patients With Atherosclerotic Disease and Heart Failure.

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) reduce the risk of cardiovascular events and heart failure hospitalization (HFH) in patients with heart failure with reduced ejection fraction (HFrEF), diabetes mellitus type 2 (DM2), and atherosclerotic cardiovascular disease (ASCVD). The role of glucagon-like peptide 1 agonists (GLP1a) in these patients is unclear. We designed this study to assess if the addition of GLP1a to SGLT2i therapy improves outcomes in patients with HFrEF, DM2, and ASCVD. This was a retrospective cohort study of patients with DM2, ASCVD, and HFrEF in the national Veterans Affairs database. Patients on SGLT2i were propensity matched to patients on both SGTL2i and GLP1a. The co-primary outcomes were HFH and the composite of all-cause death, myocardial infarction, and stroke. We assessed them through a Cox regression model including unbalanced baseline characteristics. From a cohort of 5,576 patients, 343 were propensity matched to each study arm. The addition of GLP1a was associated with a 67% reduction in the 1-year risk of a composite event compared with therapy with SGLT2i (confidence interval 0.138 to 0.714, p = 0.007). The risk of HFH was not significantly different between both arms (p = 0.199). Sensitivity analyses in the unmatched dataset confirmed these findings. In conclusion, the addition of GLP1a to SGLT2i may reduce the risk of adverse events in patients with HFrEF who have DM2 and ASCVD, but it does not affect the risk of HFH.

P2Y12 inhibitor versus aspirin monotherapy for secondary prevention of cardiovascular events: meta-analysis of randomized trials.

Aim: To compare the efficacy and safety of P2Y12 inhibitor or aspirin monotherapy for secondary prevention in patients with atherosclerotic cardiovascular disease (ASCVD). Methods and results: Medline, Embase, and Cochrane Central databases were searched to identify randomized trials comparing monotherapy with a P2Y12 inhibitor versus aspirin for secondary prevention in patients with ASCVD (cardiovascular, cerebrovascular, or peripheral artery disease). The primary outcome was major adverse cardiac events (MACE). Secondary outcomes were myocardial infarction (MI), stroke, all-cause mortality, and major bleeding. A random-effects model was used to calculate risk ratios (RR) and the corresponding 95% confidence interval (CI) and heterogeneity among studies was assessed using the Higgins I2 value. A total of 9 eligible trials (5 with clopidogrel and 4 with ticagrelor) with 61 623 patients were included in our analyses. Monotherapy with P2Y12 inhibitors significantly reduced the risk of MACE by 11% (0.89, 95% CI 0.84-0.95, I2 = 0%) and MI by 19% (0.81, 95% CI 0.71-0.92, I2 = 0%) compared with aspirin monotherapy. There was no significant difference in the risk of stroke (0.85, 95% CI 0.73-1.01), or all-cause mortality (1.01, 95% CI 0.92-1.11). There was also no significant difference in the risk of major bleeding with P2Y12 inhibitor monotherapy compared with aspirin (0.94, 95% CI 0.72-1.22, I2 = 42.6%). Results were consistent irrespective of the P2Y12 inhibitor used. Conclusion: P2Y12 inhibitor monotherapy for secondary prevention is associated with a significant reduction in atherothrombotic events compared with aspirin alone without an increased risk of major bleeding.

Meta-Analysis Comparing Venoarterial Extracorporeal Membrane Oxygenation With or Without Impella in Patients With Cardiogenic Shock.

Cardiogenic shock is associated with high short-term mortality. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used as a mechanical circulatory support strategy for patients with refractory cardiogenic shock. A drawback of this hemodynamic support strategy is increased left ventricular (LV) afterload, which is mitigated by concomitant use of Impella (extracorporeal membrane oxygenation with Impella [ECPELLA]). However, data regarding the benefits of this approach are limited. We conducted a systematic search of Medline, EMBASE, and Cochrane databases to identify studies including patients with cardiogenic shock reporting clinical outcomes with Impella plus VA-ECMO compared with VA-ECMO alone. Primary outcome was short-term all-cause mortality (in-hospital or 30-day mortality). Secondary outcomes included major bleeding, hemolysis, continuous renal replacement therapy, weaning from mechanical circulatory support, limb ischemia, and transition to destination therapy with LV assist device (LVAD) or cardiac transplant. Of 2,790 citations, 7 observational studies were included. Of 1,054 patients with cardiogenic shock, 391 were supported with ECPELLA (37%). Compared with patients on only VA-ECMO support, patients with ECPELLA had a lower risk of short-term mortality (risk ratio [RR] 0.89 [0.80 to 0.99], I2 = 0%, p = 0.04) and were significantly more likely to receive a heart transplant/LVAD (RR 2.03 [1.44 to 2.87], I2 = 0%, p <0.01). However, patients with ECPELLA had a higher risk of hemolysis (RR 2.03 [1.60 to 2.57], I2 = 0%, p <0.001), renal failure requiring continuous renal replacement therapy (RR 1.46 [1.23 to 174], I2 = 11%, p <0.0001), and limb ischemia (RR 1.67 [1.15 to 2.43], I2 = 0%, p = 0.01). In conclusion, among patients with cardiogenic shock requiring VA-ECMO support, concurrent LV unloading with Impella had a lower likelihood of short-term mortality and a higher likelihood of progression to durable LVAD or heart transplant. However, patients supported with ECPELLA had higher rates of hemolysis, limb ischemia, and renal failure requiring continuous renal replacement therapy. Future prospective randomized are needed to define the optimal treatment strategy in this high-risk cohort.

One year outcomes of atrial fibrillation ablation: Contemporary analysis of the United States Nationwide Readmission Database.

BACKGROUND: Data on long-term outcomes of catheter ablation (CA) for atrial fibrillation (AF) in outside of clinical trials settings are sparse. OBJECTIVE: We aimed to assess outcomes and readmissions at 1 year following admission for CA for AF. METHODS: Utilizing the Nationwide Readmissions Database (2016-2018), we identified patients with CA among all patients with a primary admission diagnosis of AF, and a control group by propensity score match adjusted for age, sex, comorbidities, CHA2DS2-VASc scores, and the hospital characteristics. The primary outcome was a composite of unplanned heart failure (HF), AF and stroke-related readmissions, and death at 1 year, and secondary outcomes were hospital outcomes and all-cause readmission rates. RESULTS: The study cohort consisted of 29,771 patients undergoing CA and 63,988 controls. Patients undergoing CA were younger with lower CHA2DS2-VASc scores and less comorbidities. Over a follow-up of 170 ±1.1 days, the primary outcome occurred in 5.2% in CA group and 6.0% of controls (hazard ratio [HR] and 95% confidence interval [CI]: 0.86 [0.76-0.94], p = .002). CA affected AF and stroke related readmission, but showed no effect on HF and mortality outcome. Male sex (HR: 0.83 [0.74-0.94], p = .03), younger age (HR: 0.71 [0.61-0.83], p < .001], and lower CHA2DS2-VASc scores (HR: 0.68 [0.55-0.84], p < .001) were associated with lower risk of primary outcome with CA. CONCLUSION: In this study, CA for AF was associated with significantly lower AF and stroke-related admissions, but not to HF or all-cause readmission. Better outcomes were seen among males, younger patients, and in patients with less comorbidities and low CHA2DS2-VASc scores.

Severe Obesity and Heart Failure.

Obesity is associated with reduced mortality in some patients hospitalized for heart failure (HF). In this analysis, we determine if this nonlinear relation, referred to as the obesity paradox, extends to secondary outcomes in patients diagnosed with severe obesity. This is a retrospective cohort study using the 2017 and 2018 National Inpatient Sample that includes adults hospitalized for HF. Patients with diagnosis codes specifying severe obesity, nonsevere obesity, or without obesity are compared. The primary outcome is mortality. Secondary outcomes include the length of stay (LOS), total charges, and cardiogenic shock (CS). Multivariate regression is used to adjust for demographics and co-morbidities. A total of 2,439,845 hospitalizations are included. A decreased mortality is found in nonsevere obesity (odds ratio 0.74, 95% confidence interval 0.69 to 0.80, p = 0.000), affirming the obesity paradox. However, this decreased mortality is not found in severe obesity (odds ratio 1.01, 95% confidence interval 0.94 to 1.08, p = 0.766). Severe obesity and nonsevere obesity are also associated with less CS and increased LOS compared with non-obese patients. Severe obesity is associated with increased total charges. In conclusion, a nonlinear, U-shaped relation between obesity and mortality in patients hospitalized for HF is demonstrated, where those not obese and those severely obese experience greater mortality compared with the nonseverely obese. However, for secondary outcomes of CS, LOS, and total charges, the relation is linear and therefore not interpreted as paradoxical. More information is needed using the adiposity-based chronic disease model to characterize complex relations between obesity and mortality.

Eosinophilic Myocarditis: When Allergies Attack the Heart!

Eosinophilic myocarditis is a clinical condition whereby myocardial injury is mediated by eosinophilic infiltration. A number of underlying causes, including reactive, clonal, or idiopathic hypereosinophilic syndrome, may trigger eosinophilia. Disease presentation may vary from mild subclinical variants to fulminant myocarditis with thromboembolic complications, and in some cases, endomyocardial and valvular fibrosis may be seen. A detailed examination coupled with the use of multimodality imaging, and endomyocardial biopsy may help establish diagnosis. Treatment is aimed at symptomatic management and treating the underlying cause of eosinophilia, such as withdrawal of implicated drugs, antihelminthic therapy for infection, immunosuppression for autoimmune conditions, and targeted therapy with tyrosine kinase inhibitors in cases with clonal myeloid disorders.

Temporal Trends in Characteristics and Outcomes Associated With In-Hospital Cardiac Arrest: A 20-Year Analysis (1999-2018).

Background Despite advances in resuscitation medicine, the burden of in-hospital cardiac arrest (IHCA) remains substantial. The impact of these advances and changes in resuscitation guidelines on IHCA survival remains poorly defined. To better characterize evolving patient characteristics and temporal trends in the nature and outcomes of IHCA, we undertook a 20-year analysis of a national database. Methods and Results We analyzed the National Inpatient Sample (1999-2018) using International Classification of Diseases, Ninth Revision and Tenth Revision, Clinical Modification (ICD-9-CM and ICD-10-CM) codes to identify all adult patients suffering IHCA. Subgroup analysis was performed based on the type of cardiac arrest (ie, ventricular tachycardia/ventricular fibrillation or pulseless electrical activity-asystole). An age- and sex-adjusted model and a multivariable risk-adjusted model were used to adjust for potential confounders. Over the 20-year study period, a steady increase in rates of IHCA was observed, predominantly driven by pulseless electrical activity-asystole arrest. Overall, survival rates increased by over 10% after adjusting for risk factors. In recent years (2014-2018), a similar trend toward improved survival is noted, though this only achieved statistical significance in the pulseless electrical activity-asystole cohort. Conclusions Though the ideal quality metric in IHCA is meaningful neurological recovery, survival is the first step toward this. As overall IHCA rates rise, overall survival rates are improving in tandem. However, in more recent years, these improvements have plateaued, especially in the realm of ventricular tachycardia/ventricular fibrillation-related survival. Future work is needed to better identify characteristics of IHCA nonsurvivors to improve resource allocation and health care policy in this area.

Therapeutic angiogenesis in coronary artery disease: a review of mechanisms and current approaches.

INTRODUCTION: Despite tremendous advances, the shortcomings of current therapies for coronary disease are evidenced by the fact that it remains the leading cause of death in many parts of the world. There is hence a drive to develop novel therapies to tackle this disease. Therapeutic approaches to coronary angiogenesis have long been an area of interest in lieu of its incredible, albeit unrealized potential. AREAS COVERED: This paper offers an overview of mechanisms of native angiogenesis and a description of angiogenic growth factors. It progresses to outline the advances in gene and stem cell therapy and provides a brief description of other investigational approaches to promote angiogenesis. Finally, the hurdles and limitations unique to this particular area of study are discussed. EXPERT OPINION: An effective, sustained, and safe therapeutic option for angiogenesis truly could be the paradigm shift for cardiovascular medicine. Unfortunately, clinically meaningful therapeutic options remain elusive because promising animal studies have not been replicated in human trials. The sheer complexity of this process means that numerous major hurdles remain before therapeutic angiogenesis truly makes its way from the bench to the bedside.

Current practice and future prospects in left atrial appendage occlusion.

The thromboembolic complications of Atrial fibrillation (AF) remain a major problem in contemporary clinical practice. Despite advances and developments in anticoagulation strategies, therapy is complicated by the high risk of bleeding complications and need for meticulous medication compliance. Over the past few decades, the left atrial appendage has emerged as a promising therapeutic target to prevent thromboembolic events while mitigating bleeding complications and compliance issues. Emerging data indicates that it is a safe, effective and feasible alternative to systemic anticoagulation in patients with non-valvular AF. A number of devices have been developed for endocardial or epicardial based isolation of the left atrial appendage. Increasing experience has improved overall procedural safety and ease while simultaneously reducing device related complication rates. Furthermore, increasing recognition of the non-mechanical advantages of this procedure has led to further interest in its utility for further indications beyond the prevention of thromboembolic complications. In this review, we present a comprehensive overview of the evolution of left atrial appendage occlusion, commercially available devices and the role of this modality in the current management of AF. We also provide a brief outline of the landmark trials supporting this approach as well as the ongoing research and future prospects of left atrial appendage occlusion.

Dual Antiplatelet Therapy Versus Aspirin in Patients With Stroke or Transient Ischemic Attack: Meta-Analysis of Randomized Controlled Trials.

Background and Purpose: Antiplatelet therapy is key for preventing thrombotic events after transient ischemic attack or ischemic stroke. Although the role of aspirin is well established, there is emerging evidence for the role of short-term dual antiplatelet therapy (DAPT) in preventing recurrent stroke. Methods: We conducted a systematic review and study-level meta-analyses of randomized controlled trials comparing outcomes of early initiation of short-term DAPT (aspirin+P2Y12 inhibitor for up to 3 months) versus aspirin alone in patients with acute stroke or transient ischemic attack. Primary efficacy outcome was risk of recurrent stroke and primary safety outcome was incidence of major bleeding. Secondary outcomes studied were risk of any ischemic stroke, hemorrhagic stroke, major adverse cardiovascular events, and all-cause death. Pooled risk ratios (RRs) and CIs were calculated using a random-effects model. Results: Four trials with a total of 21 459 patients were included. As compared to aspirin alone, DAPT had a lower risk of recurrent stroke (RR, 0.76 [95% CI, 0.68­0.83]; P<0.001; I2=0%) but a higher risk of major bleeding events (RR, 2.22 [95% CI, 1.14­4.34], P=0.02, I2=46.5%). Patients receiving DAPT had a lower risk of major adverse cardiovascular events (RR, 0.76 [95% CI, 0.69­0.84], P<0.001, I2=0%) and recurrent ischemic events (RR, 0.74 [95% CI, 0.67­0.82], P<0.001, I2=0%). Conclusions: As compared to aspirin alone, short-term DAPT within 24 hours of high-risk transient ischemic attack or mild-moderate ischemic stroke reduces the risk of recurrent stroke at the expense of higher risk of major bleeding.