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.

18F-FDG PET/CT in left ventricular assist device infections: In-depth characterization and clinical implications.

BACKGROUND: Previous retrospective studies suggest a good diagnostic performance of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET)/computed tomography (CT) in left ventricular assist device (LVAD) infections. Our aim was to prospectively evaluate the role of PET/CT in the characterization and impact on clinical management of LVAD infections. METHODS: A total of 40 patients (aged 58 [53-62] years) with suspected LVAD infection and 5 controls (aged 69 [64-71] years) underwent 18F-FDG-PET/CT. Four LVAD components were evaluated: exit site and subcutaneous driveline (peripheral), pump pocket, and outflow graft. The location with maximal uptake was considered the presumed site of infection. Infection was confirmed by positive culture (exit site or blood) and/or surgical findings. RESULTS: Visual uptake was present in 40 patients (100%) in the infection group vs 4 (80%) control subjects. For each individual component, the presence of uptake was more frequent in the infection than in the control group. The location of maximal uptake was most frequently the pump pocket (48%) in the infection group and the peripheral components (75%) in the control group. Maximum standard uptake values (SUVmax) were higher in the infection than in the control group: SUVmax (average all components): 6.9 (5.1-8.5) vs 3.8 (3.7-4.3), p = 0.002; SUVmax (location of maximal uptake): 10.6 ± 4.0 vs 5.4 ± 1.9, p = 0.01. Pump pocket infections were more frequent in patients with bacteremia than without bacteremia (79% vs 31%, p = 0.011). Pseudomonas (32%) and methicillin-susceptible Staphylococcus aureus (29%) were the most frequent pathogens and were associated with pump pocket infections, while Staphylococcus epidermis (11%) was associated with peripheral infections. PET/CT affected the clinical management of 83% of patients with infection, resulting in surgical debridement (8%), pump exchange (13%), and upgrade in the transplant listing status (10%), leading to 8% of urgent transplants. CONCLUSIONS: 18F-FDG-PET/CT enables the diagnosis and characterization of the extent of LVAD infections, which can significantly affect the clinical management of these patients.

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.

Recent Advances in Stent Technology: Do They Reduce Cardiovascular Events?

PURPOSE OF REVIEW: Drug-eluting stents are used in nearly all cases of percutaneous coronary revascularization and have been shown to be superior to balloon angioplasty or bare metal stents. The designs of these stents are continually evolving to maximize efficacy and safety. RECENT FINDINGS: This review outlines the important components of a drug-eluting stent and highlights the changes in stent design that have led to the optimization of clinical outcomes. Most stents used in contemporary times are thin strut, durable polymer drug-eluting stents (DES) that elute either everolimus or zotarolimus. Newer DES designs incorporating bioresorbable polymers or ultrathin struts have shown encouraging safety and efficacy profiles. DES are essential for the management of patients with obstructive coronary artery disease and are used in most coronary interventions. Changes in stent designs over the past 30 years reflect the ongoing need to address the limitations of earlier stents aimed to improve patient outcomes.

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.

Cardio-renal benefits of sodium-glucose co-transporter 2 inhibitors in heart failure with reduced ejection fraction: mechanisms and clinical evidence.

The heart and the kidneys are closely interconnected, and disease in one organ system can lead to disease in the other. This interdependence is illustrated in heart failure with reduced ejection fraction (HFrEF), where worsening heart failure (HF) can lead to renal dysfunction and vice versa. Further complicating this situation is the fact that drugs that serve as guideline-directed medical therapy for HFrEF can affect renal function. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new class of medication with an evolving role in HF and chronic kidney disease (CKD). Initially found to have benefits in diabetic patients, new research established potential cardiovascular and renal benefits in patients with HF independent of their diabetic status and in populations with CKD. This has been established by landmark trials such as EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure and a Reduced Ejection Fraction), EMPA-TROPISM (Are the 'Cardiac Benefits' of Empagliflozin Independent of Its Hypoglycemic Activity), CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation), DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease), DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure), and DEFINE-HF (Dapagliflozin Effects on Biomarkers, Symptoms and Functional Status in Patients with HF with Reduced Ejection Fraction). Multiple mechanisms responsible for these benefits have been suggested by clinical and non-clinical studies, and involve cardiac and renal energetic efficiency, cardiac remodelling, preservation of renal function, immunomodulation, changes in haematocrit, and control of risk factors. As such, SGLT2 inhibitors have tremendous potential to improve outcomes in populations with HF and CKD. The purpose of this review is to discuss the current evidence and underlying mechanisms for the cardio-renal benefits of SGLT2 inhibitors in patients with HFrEF.

Incidence and Predictors of Sudden Cardiac Arrest in Sarcoidosis: A Nationwide Analysis.

OBJECTIVES: This study sought to identify electrocardiographic (ECG) and clinical predictors of sudden cardiac arrest (SCA) in sarcoidosis. BACKGROUND: Sudden cardiac death (SCD) is the leading cause of death in cardiac sarcoidosis (CS) and may be the earliest manifestation of disease. Widespread or repeated advanced imaging is a challenging solution to this problem. ECG is an affordable and widely accessible modality that could help guide diagnostic approaches and risk stratification. METHODS: Data were obtained from the National Inpatient Sample (2005-2017) using International Classification of Diseases-9th Revision and -10th Revision-Clinical Modification. The primary outcome was to identify predictors of SCA, whereas predictors of SCA in young individuals and those with normal ventricular function served as secondary measures. Furthermore, temporal trends in sarcoidosis as well as SCA were also analyzed. Logistic regression analysis was used to calculate odds ratios, following which a multivariable regression was used to adjust for potential confounders. RESULTS: Electrocardiographic markers of AV node dysfunction or bundle branch block are associated with substantially increased risk of SCA in a limited proportion of patients (8.6%). This association is also observed among younger patients (<40 years) and those with normal ventricular function. CONCLUSIONS: ECG evidence of AV nodal dysfunction or distal conduction disease should raise suspicion for cardiac involvement in patients with sarcoidosis and are associated with increased risk of SCA. ECG markers could help identify patients who would benefit from advanced imaging. The sensitivity of ECGs is, however, limited and presence of a normal ECG does not reflect a low risk of SCA.

Pharmacotherapeutic principles of fluid management in heart failure.

Introduction: Heart failure is a major public health concern that is expected to increase over the decades to come. Despite significant advances, fluid overload and congestion remain a major therapeutic challenge. Vascular congestion and neurohormonal activation are intricately linked and the goal of therapy fundamentally aims to reduce both.Areas covered: The authors briefly review a number of core concepts that elucidate the link between fluid overload and neuro-hormonal activation. This is followed by a review of heart-kidney interactions and the impact of diuresis in this setting. Following an in-depth review of currently available pharmacological agents, the rationale and evidence behind their use, the authors end with a brief note on novel agents/approaches to aid volume management in HF.Expert opinion: A number of non-pharmacological advances in the management of volume overload in heart failure, though promising - are associated with a number of shortcomings. Pharmacological therapy remains the cornerstone of volume management. A number of novel approaches, utilizing existing therapies as well as the emergence of new agents over the past decade bode well for the vulnerable HF population.

Does the use of intracardiac echocardiography during atrial fibrillation catheter ablation improve outcomes and cost? A nationwide 14-year analysis from 2001 to 2014.

BACKGROUND: Intracardiac echocardiography (ICE) use during catheter ablation of atrial fibrillation (AF) provides real-time information to guide transseptal access, for monitoring the ablation and recognition of pericardial bleed. We describe trends of ICE use, impact on complications, and its in-hospital outcomes. METHODS: The national in-patient sample database was queried from 2001 to 2014 for diagnosis of AF based on ICD-9-CM 427.31 with a catheter ablation procedure code (37.34) in the same hospitalization and its associated complications. ICE was identified using ICD-9-CM procedure code (37.28). Statistical Analysis System (SAS) was used for analysis. RESULTS: There was an estimated total 299,152 patients who underwent AF ablation from 2001 to 2014 of which ICE was used in 46,688 (15.6%) patients. The use of ICE significantly increased from 0.08% in 2001 to 15.7% in 2014. In-hospital mortality was significantly lower in patients in whom ICE was used (0.11% vs 0.54%, p < 0.0001). Complications were 52% lower in procedures using ICE vs without ICE (HR [95%CI]; 0.48 [0.44-0.51]). The rate of cardiac complications was also lower in ICE users (3.67% vs 4.51%; p = 0.025). The use of ICE during AF ablation resulted in significantly higher cost of hospitalization ($98,436 ± 597 vs $81,300 ± 310; p < 0.0001), but this was offset by a decreased length of hospital stay (2.1 ± 0.02 vs 4 ± 0.02 days; p < 0.0001). CONCLUSIONS: The use of ICE during AF ablation has increased over the years and is associated with lower in-hospital mortality and procedural complications, shorter LOS but an increased cost of hospitalization.

Trends, burden, and impact of arrhythmia on cardiac amyloid patients: A 16-year nationwide study from 1999 to 2014.

BACKGROUND: Patients with cardiac amyloidosis (CA) have increased mortality, which can be explained in part by an increased risk of arrhythmias. The burden of arrhythmias in CA, their predictors, and impact on in-hospital outcomes remains unclear. The role of implantable cardioverter-defibrillators (ICD) in this population is also uncertain. METHODS: We queried the National Inpatient Sample (NIS) using ICD-9-CM codes 277.39 and 425.7 to identify CA. Twelve common arrhythmias were extracted using appropriate, validated ICD-9-CM codes. ICD implantation was identified using procedure ICD-9 codes 37.94 to 37.98, 00.51 and 00.54. RESULTS: There were a total of 145,920 CA hospitalizations between 1999 and 2014 in the United States and 56,199 (38.5%) of them were associated with arrhythmias. The prevalence of arrhythmias remained relatively constant from 41.5% in 1999 to 40.2% in 2014. The most common arrhythmia was atrial fibrillation (25.4%). In-patient mortality was significantly higher in CA patients with arrhythmias (10.4% vs 6.5%, P < .001). ICD implantation was performed in 1,381 (0.94%) patients with CA and analysis revealed an incremental trend in implantation over the study period (0.48% in 1999 to 0.65% in 2014). In-hospital mortality was significantly lower in patients who underwent ICD implantation (3.7% vs 8%; P = .0078). CA patients with arrhythmias also had an increased cost of hospitalization and length of stay ($65,046 ± 1,079 vs $53,322 ± 687 and 8.3 ± 0.1 vs 7.4 ± 0.1 days, respectively; P < .0001). CONCLUSION: Cardiac arrhythmias are common in patients with CA and are associated with worse in-hospital outcomes, increased length of stay, and cost of hospitalization.

Current pharmacotherapeutic strategies for cardiac arrhythmias in heart failure.

Introduction: Heart failure (HF) affects over 6 million Americans and is the most common cause of hospital readmissions in the United States. Cardiac arrhythmias are common comorbidities seen in patients with HF and are associated with an increase in morbidity and mortality. Pharmacotherapeutic agents along with device and ablation therapies are the mainstays of treatment for cardiac arrhythmias in HF.Areas covered: An extensive literature review of articles and clinical trials on PUBMED on the topic of pharmacotherapy for cardiac arrhythmias in heart failure was conducted. This review article summarizes the above literature to describe the prevalence of the various types of arrhythmias in HF, the recommended pharmacotherapies for the treatment of these arrhythmias in HF and the evidence that supports these recommendations.Expert opinion: Cardiac arrhythmias are common in HF and are the leading cause of death in this patient population. The management of cardiac arrhythmias in HF is challenging. Pharmacotherapy is the primary though increasingly adjunctive therapy for most cardiac arrhythmias. Further, antiarrhythmic drugs must be used with caution in this patient population due to their potential adverse effects.

Manipulation of ACE2 expression in COVID-19.

SARS-CoV-2 is the virus responsible for the ongoing COVID-19 outbreak. The virus uses ACE2 receptor for viral entry. ACE2 is part of the counter-regulatory renin-angiotensin-aldosterone system and is also expressed in the lower respiratory tract along the alveolar epithelium. There is, however, significant controversy regarding the role of ACE2 expression in COVID-19 pathogenesis. Some have argued that decreasing ACE2 expression would result in decreased susceptibility to the virus by decreasing available binding sites for SARS-CoV-2 and restricting viral entry into the cells. Others have argued that, like the pathogenesis of other viral pneumonias, including those stemming from previous severe acute respiratory syndrome (SARS) viruses, once SARS-CoV-2 binds to ACE2, it downregulates ACE2 expression. Lack of the favourable effects of ACE2 might exaggerate lung injury by a variety of mechanisms. In order to help address this controversy, we conducted a literature search and review of relevant preclinical and clinical publications pertaining to SARS-CoV-2, COVID-19, ACE2, viral pneumonia, SARS, acute respiratory distress syndrome and lung injury. Our review suggests, although controversial, that patients at increased susceptibility to COVID-19 complications may have reduced baseline ACE2, and by modulating ACE2 expression one can possibly improve COVID-19 outcomes. Herein, we elucidate why and how this potential mechanism might work.