Outcomes of Transvenous Lead Extraction in a Referral Center in Northern Israel.

BACKGROUND: Cardiac implantable electronic devices (CIEDs) are increasingly being used; thus, there is an increasing need for transvenous lead extraction (TLE). OBJECTIVES: To summarize our experience with TLE at single referral center in northern Israel. METHODS: The study included all patients who underwent TLE at our center between 2019 and 2022, regardless of the indication. RESULTS: The cohort included 50 patients. The mean age was 69 ± 10.36 years; 78% were males. A total of 99 electrodes were targeted. The mean number of electrodes was 1.96 (range 1-4) per patient. The time between lead implantation and extraction ranged between 1.1 and 34 years with an average of 8.14 ± 5.71 years (median of 7.5 years). Complete lead removal was achieved in 98% of patients and in 98.99% of leads. The complete procedural success rate as well as the clinical procedural success rate was 96%. The procedural failure rate was 4% (1 patient died 2 days after the index procedure and 1 patient remained with large portion of lead). The indication for TLE was infection in 78% of the cohort group. Powered mechanical sheaths were used in 36 patients (72%), laser sheaths in 27 (54%), and a combination of laser and mechanical sheaths in 16 (32%). CONCLUSIONS: The clinical and procedural success rates of TLE, primarily for CEID-related infection, were high. A combination of laser and mechanical sheaths was needed in one-third of patients.

Emergency Department Use and Hospital Mortality Among Heart Transplant Recipients in the United States.

BACKGROUND: Annual heart transplant (HT) volumes have increased, as have post-HT outpatient care needs. Data on HT-related emergency department (ED) visits are limited. METHODS AND RESULTS: A retrospective analysis of 177 450 HT patient ED visits from the 2009 to 2018 Nationwide Emergency Department Sample was conducted. HT recipients, primary diagnoses, and comorbidities associated with ED visits were identified via International Classification of Diseases, Ninth Revision (ICD-9) and International Classification of Diseases, Tenth Revision (ICD-10) codes. Multivariable logistic regression was used to predict outcomes of hospital admission and death. HT volumes and HT-related ED visits increased from 2009 to 2018. Infection was the most common primary diagnosis (24%), and cardiac primary diagnoses represented 10% of encounters. Hospital admissions occurred in 48% of visits, but overall mortality was low (1.6%). Length of stay was 3.1 days (interquartile range, 1.6-5.9 days), and comorbidity burden was high: 42% had hypertension, 38% had diabetes, and 31% had ≥2 comorbidities. Those aged ≥65 years had significantly higher odds of admission (odds ratio [OR], 2.14 [95% CI, 1.97-2.33]) and death (OR, 2.06 [95% CI, 1.61-2.62]). Comorbidities increased odds of admission (OR, 1.62 [95% CI, 1.51-1.75]) but not death. Renal primary diagnosis had the highest risk of admission (OR, 4.1 [95% CI, 3.6-4.6]), but cardiac primary diagnosis had the highest odds of death (OR, 11.6 [95% CI, 9.1-14.8]). CONCLUSIONS: HT-related ED visits increased from 2009 to 2018 with high admission rates but low in-hospital mortality, suggesting an opportunity to improve prehospital care. Older patients and those with cardiac primary diagnoses had the highest risk of death. The observed contrast between predictors of admission and mortality signals a need for further study to improve risk stratification and outpatient care strategies.

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.

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.

Chronotropic Incompetence after Heart Transplantation Is Associated with Increased Mortality and Decreased Functional Capacity.

INTRODUCTION: The contribution of chronotropic incompetence to reduced exercise tolerance after a heart transplant is well known, but its role as a prognostic marker of post-transplant mortality is unclear. The aim of this study is to examine the relationship between post-transplant heart rate response (HRR) and survival. METHODS: We performed a retrospective analysis of all adult heart transplant recipients at the University of Pennsylvania between the years 2000 and 2011 who underwent a cardiopulmonary exercise test (CPET) within a year of transplant. Follow-up time and survival status were observed through October 2019, using data merged from the Penn Transplant Institute. HRR was calculated by subtracting the resting HR from the peak exercise HR. The association between HRR and mortality was analyzed using Cox proportional hazard models and Kaplan-Meier analysis. The optimal cut-off point for HRR was generated by Harrell's C statistic. Patients with submaximal exercise tests were excluded, defined by a respiratory exchange ratio (RER) cut-off of 1.05. RESULTS: Of 277 patients with CPETs performed within a year post-transplant, 67 were excluded for submaximal exercise. In the 210 included patients, the mean follow-up time was 10.9 years (Interquartile range (IQR) 7.8-14). Resting HR and peak HR did not significantly impact mortality after adjusting for covariates. In a multivariable linear regression analysis, each 10-beat increase in heart rate response was associated with a 1.3 mL/kg/min increase in peak VO2 and a 48 s increase in the total exercise time. Each beat/min increase in HRR was associated with a 3% reduction in the hazard of mortality (HR 0.97; 95% CI 0.96-0.99, p = 0.002). Using the optimal cut-off point generated by Harrell's C statistic, survival was significantly higher in patients with an HRR > 35 beats/min compared to those with an HRR < 35 beats/min (log rank p = 0.0012). CONCLUSION: In heart transplant patients, a low HRR is associated with increased all-cause mortality and decreased exercise capacity. Additional studies are needed to validate whether targeting HRR in cardiac rehabilitation may improve outcomes.

The Prognostic Value of Cardiovascular Risk Factors and Laboratory Biomarkers in Predicting 6-Month Outcomes in High-risk Patients with Non-ST Segment Elevation Myocardial Infarction.

BACKGROUND: Acute coronary syndrome (ACS) represents a spectrum of ischemic myocardial disease including unstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI), and ST-elevation myocardial infarction (STEMI). Various prognostic scores were developed for patients presenting with NSTEMI-ACS. Among these scores, the GRACE risk score offers the best discriminative performance for prediction of in-hospital and 6-month mortality. However, the GRACE score is limited and cannot be used in several ethnic populations. Moreover, it is not predictive of clinical outcomes other than mortality. OBJECTIVES: To assess the prognostic value of traditional cardiovascular risk factors and laboratory biomarkers in predicting 6-month major adverse cardiac and cerebrovascular events (MACCE), including hospitalization, recurrent percutaneous coronary intervention (PCI), stroke, and cardiovascular mortality in patients with NSTEMI treated with PCI. METHODS: This retrospective study included consecutive patients admitted with an initial diagnosis of NSTEMI to the cardiac intensive care unit (CICU) at the Tzafon Medical Center, Israel, between April 2015 and August 2018 and treated by PCI within 48 hours of admission. RESULTS: A total of 223 consecutive patients with NSTEMI treated by PCI were included in the study. Logarithmebrain natriuretic peptide (LogₑBNP), prior MI, and Hb levels were found to be significant predictors of any first MACCE. Only logₑBNP was found to be an independent predictor of a first MACCE event by multivariate logistic regression analysis. CONCLUSIONS: LogₑBNP is an independent predictor of worse prognosis in patients with NSTEMI. Routine evaluation of BNP levels should be considered in patients admitted with NSTEMI.

The Effects of Preoperative Pain Education on Pain Severity in Cardiac Surgery Patients: A Pilot Randomized Control Trial.

BACKGROUND: There is minimal research on the effect of individualized preoperative education on postoperative pain and postoperative pain medication intake. AIM: The study objective was to assess the effect of individually tailored preoperative education on postoperative pain severity, number of pain breakthroughs, and use of pain medication in participants receiving the intervention compared to controls. METHODS: A pilot study with 200 participants was conducted. The experimental group received an informational booklet and discussed their ideas surrounding pain and pain medication with the researcher. Controls received no intervention. Postoperative pain severity was measured by a Numerical Rating System (NRS), which was divided into mild (NRS 1-3), moderate (NRS 4-6), and severe (NRS 7-10). RESULTS: In the participant cohort, 68.8% of participants were male, and the average age was 60.48±10.7. Average postoperative 48-hour cumulative pain scores were lower in those who received the intervention compared to controls; 50.0 (IQR 35.8-60.0) vs. 65 (IQR 51.0-73.0; p < .01) participants who received the intervention had less frequent pain breakthroughs when compared to controls (3.0 [IQR 2.0-5.0] vs. 6.0 [IQR 4.0-8.0; p < .01]). There was no significant difference in the amount of pain medication taken by either group. CONCLUSIONS: Participants who receive individualized preoperative pain education are more likely to have decreased postoperative pain.

Durable Left Ventricular Assist Device Outflow Graft Obstructions: Clinical Characteristics and Outcomes.

PURPOSE: We report on the clinical course and management of patients supported with durable implantable LVADs who developed outflow graft obstructions at a large academic center. METHODS: We performed a retrospective review of patients receiving LVAD support from 2012 through 2020. Patients who developed an outflow graft obstruction diagnosed by computed tomography angiography (CTA) or angiogram were identified, and patient characteristics and outcomes were reported. RESULTS: Of the 324 patients supported by LVAD at our institution, 11 patients (3.4%) were diagnosed with outflow graft obstructions. The most common presentation was low flow alarms, which was present in 10/11 patients, and the remaining patient presented with lightheadedness. Patients had minimal LDH elevation with 8/11 presenting with less than 2-fold the upper limit of normal. Transthoracic echocardiograms were not diagnostic, but CTA enabled non-invasive diagnoses in 8/11 of the patients. Three patients with extrinsic compression of the outflow graft successfully underwent endovascular stent placement, and three patients with outflow cannula kinks received supportive care. Of the five patients diagnosed with intraluminal thromboses, one received a heart transplant, one underwent an outflow graft revision, and three received supportive care due to comorbidities. CONCLUSION: Outflow graft obstructions remain a rare, but serious complication. The true prevalence of this entity is likely underestimated due to the non-specific clinical presentation. CTA is a pivotal non-invasive diagnostic step. Patients with external compression were successfully treated with endovascular stenting.

Ascites in Animals With Right Heart Failure: Correlation With Lymphatic Dysfunction.

Background Congestive heart failure is a leading cause of morbidity and mortality worldwide. One of the signs of congestive heart failure is fluid overload including pulmonary edema, peripheral edema, and ascites. The cause of fluid overload remains incompletely understood, and management of these patients continues to be a challenge. The role of lymphatic circulation abnormalities in the cause and pathophysiology of fluid overload also remains unclear. Here we report on a study in a large animal model of right heart failure caused by severe tricuspid regurgitation comparing cardiovascular and lymphatic findings in a group of animals that did not develop ascites with a group of animals that developed ascites. Methods and Results Thirteen Yorkshire pigs were included in this study divided into 2 groups. Group 1 included 6 animals that did not develop ascites, and Group 2 included 7 animals that had developed ascites. The groups were compared on hemodynamic parameters as well as comparison of the animal's lymphatic anatomy and function. There was no difference between the groups in degree of tricuspid regurgitation and central venous pressure, with inferior vena cava pressure measuring 11.6±1.6 versus 13.2±3.7 (P=0.534) and superior vena cava pressure measuring 12.0±2.3 versus 13.7±3.2 (P=0.366). There was also no difference between the groups in all measured hemodynamic parameters, including right ventricular pressure, pulmonary artery pressure, and left ventricular function. The weighted liver size in the ascites group was significantly larger than in the nonascites group (30.3±12.4 versus 63.3±14.0 mL/kg, respectively; P=0.001). The 2 groups also differed in the number of animals with regurgitant thoracic duct flow (Group 1: 1/6,17% versus Group 2: 6/7, 86%; P=0.029) and the minimal thoracic duct diameter (Group 1: 2.3±0.3 versus Group 2: 4.2±2.2; P=0.035). Conclusions In animals with right heart failure caused by severe tricuspid regurgitation, fluid overload did not correlate with hemodynamic parameters but rather with changes in the lymphatic system, including regurgitant lymphatic flow, minimal thoracic duct diameter, and liver size. This study is consistent with lymphatic dysfunction and not cardiovascular function playing a significant role in the cause of fluid overload. Further studies are needed to confirm these findings.

Left Ventricular "Longitudinal Rotation" and Conduction Abnormalities-A New Outlook on Dyssynchrony.

BACKGROUND: The complete left bundle branch block (CLBBB) results in ventricular dyssynchrony and a reduction in systolic and diastolic efficiency. We noticed a distinct clockwise rotation of the left ventricle (LV) in patients with CLBBB ("longitudinal rotation"). AIM: The aim of this study was to quantify the "longitudinal rotation" of the LV in patients with CLBBB in comparison to patients with normal conduction or complete right bundle branch block (CRBBB). METHODS: Sixty consecutive patients with normal QRS, CRBBB, or CLBBB were included. Stored raw data DICOM 2D apical-4 chambers view images cine clips were analyzed using EchoPac plugin version 203 (GE Vingmed Ultrasound AS, Horten, Norway). In EchoPac-Q-Analysis, 2D strain application was selected. Instead of apical view algorithms, the SAX-MV (short axis-mitral valve level) algorithm was selected for analysis. A closed loop endocardial contour was drawn to initiate the analysis. The "posterior" segment (representing the mitral valve) was excluded before finalizing the analysis. Longitudinal rotation direction, peak angle, and time-to-peak rotation were recorded. RESULTS: All patients with CLBBB (n = 21) had clockwise longitudinal rotation with mean four chamber peak rotation angle of -3.9 ± 2.4°. This rotation is significantly larger than in patients with normal QRS (-1.4 ± 3°, p = 0.005) and CRBBB (0.1 ± 2.2°, p = 0.00001). Clockwise rotation was found to be correlated to QRS duration in patients with the non-RBBB pattern. The angle of rotation was not associated with a lower ejection fraction or the presence of regional wall abnormalities. CONCLUSIONS: Significant clockwise longitudinal rotation was found in CLBBB patients compared to normal QRS or CRBBB patients using speckle-tracking echocardiography.

Early Cardiopulmonary Fitness after Heart Transplantation as a Determinant of Post-Transplant Survival.

BACKGROUND: Decreased peak oxygen consumption during exercise (peak Vo2) is a well-established prognostic marker for mortality in ambulatory heart failure. After heart transplantation, the utility of peak Vo2 as a marker of post-transplant survival is not well established. METHODS AND RESULTS: We performed a retrospective analysis of adult heart transplant recipients at the Hospital of the University of Pennsylvania who underwent cardiopulmonary exercise testing within a year of transplant between the years 2000 to 2011. Using time-to-event models, we analyzed the hazard of mortality over nearly two decades of follow-up as a function of post-transplant percent predicted peak Vo2 (%Vo2). A total of 235 patients met inclusion criteria. The median post-transplant %Vo2 was 49% (IQR 42 to 60). Each standard deviation (±14%) increase in %Vo2 was associated with a 32% decrease in mortality in adjusted models (HR 0.68, 95% CI 0.53 to 0.87, p = 0.002). A %Vo2 below 29%, 64% and 88% predicted less than 80% survival at 5, 10, and 15 years, respectively. CONCLUSIONS: Post-transplant peak Vo2 is a highly significant prognostic marker for long-term post-transplant survival. It remains to be seen whether decreased peak Vo2 post-transplant is modifiable as a target to improve post-transplant longevity.

Effects of Body Mass Index on Presentation and Outcomes of COVID-19 among Heart Transplant and Left Ventricular Assist Device Patients: A Multi-Institutional Study.

The coronavirus disease 2019 (COVID-19) pandemic continues to pose a significant threat to patients receiving advanced heart failure therapies. The current study was undertaken to better understand the relationship between obesity and outcomes of SARS-CoV-2 infection in patients with a left ventricular assist device (LVAD) or heart transplant. We performed a retrospective review of patients with a heart transplant or LVAD who presented to one of the participating 11 institutions between April 1 and November 30, 2020. Patients were grouped by body mass index (BMI) into obese (BMI ≥ 30 k/m2) and nonobese cohorts (BMI < 30 kg/m2). Multivariable logistic regression models were used to estimate effects of obesity on outcomes of interest. Across all centers, 162 heart transplant and 81 LVAD patients were identified; 54 (33%) and 38 (47%) were obese, respectively. Obese patients tended to have more symptoms at presentation. No differences in rates of hospitalization or ICU admission were noted. Obese patients with LVADs were more likely to require mechanical ventilation (39% vs. 8%, p < 0.05). No differences in renal failure or secondary infection were noted. Mortality was similar among heart transplant patients (11% [obese] vs. 16% [nonobese], p = 0.628) and LVAD patients (12% vs. 15%, p = 1.0). BMI was not associated with increased adjusted odds of mortality, ICU admission, or mechanical ventilation (all p > 0.10). In summary, acute presentations of SARS-CoV-2 among heart transplant and LVAD recipients carry a significantly higher mortality than the general population, although BMI does not appear to impact this. Further studies on the longer-term effects of COVID-19 on this population are warranted.

Left Ventricular Assist Devices: A Primer For the General Cardiologist.

Durable implantable left ventricular assist devices (LVADs) have been shown to improve survival and quality of life for patients with stage D heart failure. Even though LVADs remain underused overall, the number of patients with heart failure supported with LVADs is steadily increasing. Therefore, general cardiologists will increasingly encounter these patients. In this review, we provide an overview of the field of durable LVADs. We discuss which patients should be referred for consideration of advanced heart failure therapies. We summarize the basic principles of LVAD care, including medical and surgical considerations. We also discuss the common complications associated with LVAD therapy, including bleeding, infections, thrombotic issues, and neurologic events. Our goal is to provide a primer for the general cardiologist in the recognition of patients who could benefit from LVADs and in the principles of managing patients with LVAD. Our hope is to "demystify" LVADs for the general cardiologist.

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.

Hemodynamic reserve predicts early right heart failure after LVAD implantation.

BACKGROUND: Early right heart failure (RHF) remains a major source of morbidity and mortality after left ventricular assist device (LVAD) implantation, yet efforts to predict early RHF have proven only modestly successful. Pharmacologic unloading of the left ventricle may be a risk stratification approach allowing for assessment of right ventricular and hemodynamic reserve. METHODS: We performed a multicenter, retrospective analysis of patients who had undergone continuous-flow LVAD implantation from October 2011 to April 2020. Only those who underwent vasodilator testing with nitroprusside during their preimplant right heart catheterization were included (n = 70). Multivariable logistic regression was used to determine independent predictors of early RHF as defined by Mechanical Circulatory Support-Academic Research Consortium. RESULTS: Twenty-seven patients experienced post-LVAD early RHF (39%). Baseline clinical characteristics were similar between patients with and without RHF. Patients without RHF, however, achieved higher peak stroke volume index (SVI) (30.1 ± 8.8 vs 21.7 ± 7.4 mL/m2; p < 0.001; AUC: 0.78; optimal cut-point: 22.1 mL/m2) during nitroprusside administration. Multivariable analysis revealed that peak SVI was significantly associated with early RHF, demonstrating a 16% increase in risk of early RHF per 1 ml/m2 decrease in SVI. A follow up cohort of 10 consecutive patients from July 2020 to October 2021 resulted in all patients being categorized appropriately in regards to early RHF versus no RHF according to peak SVI. CONCLUSION: Peak SVI with nitroprusside administration was independently associated with post-LVAD early RHF while resting hemodynamics were not. Vasodilator testing may prove to be a strong risk stratification tool when assessing LVAD candidacy though additional prospective validation is needed.

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.

Use and Out-of-Pocket Cost of Sacubitril-Valsartan in Patients With Heart Failure.

Background Current guidelines recommend use of sacubitril-valsartan in patients with heart failure with reduced ejection fraction (HFrEF). Early data suggested low uptake of sacubitril-valsartan, but contemporary data on real-world use and their associated cost are limited. Methods and Results This was a retrospective study of individuals enrolled in Optum Clinformatics, a national insurance claims data set from 2016 to 2018. We included all adult patients with HFrEF with 2 outpatient encounters or 1 inpatient encounter with an International Classification of Diseases, Tenth Revision (ICD-10), diagnosis of HFrEF and 6 months of continuous enrollment, also receiving ß-blockers and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers within 6 months of HFrEF diagnosis. We included 70 245 patients with HFrEF, and 5217 patients (7.4%) received sacubitril-valsartan prescriptions. Patients receiving care through a cardiologist compared with a primary care physician alone were more likely to receive sacubitril-valsartan (odds ratio, 1.61 [95% CI, 1.52-1.71]). Monthly out-of-pocket (OOP) cost for sacubitril-valsartan, compared with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, was higher for both commercially insured patients (mean, $69 versus $6.74) and Medicare Advantage (mean, $62 versus $2.52). For patients with commercial insurance, OOP cost was lower in 2016 than in 2018. For patients with Medicare Advantage, there was a significant geographic variation in the OOP costs across the country, ranging from $31 to $68 per month across different regions, holding all other patient-related factors constant. Conclusions Sacubitril-valsartan use was infrequent among patients with HFrEF. Patients receiving care with a cardiologist were more likely to receive sacubitril-valsartan. OOP costs remain high, potentially limiting use. Significant geographic variation in OOP costs, unexplained by patient factors, was noted.