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.

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.

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.

The Anemia Stress Index-Anemia, Transfusions, and Mortality in Patients with Continuous Flow Ventricular Assist Devices.

We aimed to identify a simple metric accounting for peri-procedural hemoglobin changes, independent of blood product transfusion strategies, and assess its correlation with outcomes in patients undergoing left ventricular assist device (LVAD) implantation We included consecutive patients undergoing LVAD implantation at a single center between 10/1/2008 and 6/1/2014. The anemia stress index (ASI), defined as the sum of number of packed red blood cells transfused and the hemoglobin changes after LVAD implantation, was calculated for each patient at 24 h, discharge, and 3 months after LVAD implantation. Our cohort included 166 patients (80.1% males, mean age 56.3 ± 15.6 years) followed up for a median of 12.3 months. Increases in ASI per unit were associated with a higher hazard for all-cause mortality and early RV failure. The associations between the ASI and all-cause mortality persisted after multivariable adjustment, irrespective of when it was calculated (adjusted HR of 1.11, 95% CI 1.03-1.20 per unit increase in ASI). Similarly, ASI at 24 h after implant was associated with early RV failure despite multivariable adjustment (OR 1.09, 95% CI 1.05-1.14). We present a novel metric, the ASI, that is correlated with an increased risk for all-cause mortality and early RV failure in LVAD recipients.

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.

Clinically Ambiguous Hemorrhagic Cardiac Tamponade Associated with Apixaban.

Hemorrhagic cardiac tamponade in the setting of direct oral anticoagulants (DOACs) is rare but life-threatening. Presentation in subacute cases can also be nonspecific, which can potentially delay diagnosis. A 60-year-old female with a history of heart failure and chronic obstructive pulmonary disease presented with shortness of breath, chest pain, and cough while on treatment with apixaban after a recent hospitalization for pulmonary embolism. Clinical presentation was consistent with multiple diagnoses, including pneumonia and heart failure exacerbation. However, there were several risk factors for hemopericardium with DOACs such as elevated creatinine, hypertension, elevated international normalized ratio (INR), and concomitant use of medications with similar metabolic pathways as apixaban. In addition, subtle findings on examination such as oximetry paradoxus and electrical alternans were crucial for an early diagnosis and management. In this case, we discuss key characteristics of hemopericardium with DOACs, as well as considerations on its management.

No survival benefit associated with waiting for non-lung donor heart transplants for adult recipients with congenital heart disease.

BACKGROUND: Adults with congenital heart disease (CHD) awaiting heart transplant (HT) have higher mortality and waitlist removal due to clinical deterioration than those without CHD. The selective use of non-lung donors (NLD) to recover donor pulmonary vasculature to assist in graft implantation may be a contributing factor and is supported by consensus statements despite the recent use of pericardium or graft material as an alternative in pulmonary vascular reconstruction. The impact of selecting NLD for CHD recipients on wait time and mortality has not been evaluated. METHODS/RESULTS: In the United Network for Organ Sharing (UNOS) Registry, 1271 HT recipients age ≥ 18 with CHD were identified between 1987 and 2016, 68% of which had NLDs. Prior to HT, NLD recipients were significantly less likely to be listed UNOS Status 1A, require mechanical ventilation, or intra-aortic balloon pump support. There was no difference in mean waitlist time (254 vs. 278 days, p = .31), 1-year mortality (82% vs. 80%, p = .81; adjusted odds ratio 1.32, 95% confidence interval [CI] 0.96-1.83, p = .08), or overall mortality (adjusted hazard ratio 1.08, 95% CI 0.86-1.36, p = .48) between recipients from NLD and concomitant lung donors. CONCLUSIONS: Adult CHD patients who are less critically ill or listed at a lower status are more likely to receive HT from NLD. There is no overall mortality benefit associated with this practice. While specific cases may necessitate waiting for NLD, programs need to re-evaluate whether this should remain a more widespread practice among CHD patients.

Prevention of heart failure events with sodium-glucose co-transporter 2 inhibitors across a spectrum of cardio-renal-metabolic risk.

AIMS: Trials have tested the safety and efficacy of sodium-glucose co-transporter 2 inhibitors (SGLT2i) across various disease states. We performed a meta-analysis of randomized controlled trials (RCTs) to estimate the relative and absolute effects of SGLT2i in the prevention of heart failure (HF) events across different risk groups. METHODS AND RESULTS: We conducted a systematic review and meta-analysis of large, placebo-controlled RCTs with >1000 participants evaluating HF hospitalization and the composite of cardiovascular (CV) death or HF hospitalization. Due to varying durations of therapeutic exposure and follow-up, absolute risk reductions and number needed to treat were calculated based on incidence rates (per 100 patient-years). Across 71 553 patients enrolled in 10 late-phase RCTs, SGLT2i reduced the risk of HF hospitalization by 31% [hazard ratio (HR) 0.69, 95% confidence interval (CI) 0.64-0.74; I2  = 0%] and the composite outcome of CV death or HF hospitalization by 24% (HR 0.76, 95% CI 0.72-0.80; I2  = 1.4%) compared with placebo. The number of patient-years of treatment exposure needed to prevent one CV death or HF hospitalization ranged from 19-26 (established HF) to 72-125 (chronic kidney disease) to 96-400 (high-risk type 2 diabetes). In mixed-effects meta-regression analyses, the benefits of SGLT2i on HF hospitalizations or the composite outcome (CV death or HF hospitalization) were not influenced by age, sex, or change in intermediate markers (glycated haemoglobin, systolic blood pressure, and body weight) (all P ≥ 0.10). CONCLUSION: Despite wide variation in baseline risks and disease states evaluated, SGLT2i demonstrated comparable relative risk reductions in preventing HF events. Patients at highest baseline risk derived the greatest absolute benefits in preventing HF events. These composite estimates may help guide targeted implementation of SGLT2i for the prevention of HF events in type 2 diabetes and chronic kidney disease and in the treatment of HF.

Rapid Deterioration of Hospital-Acquired COVID-19 in a Patient on Extracorporeal Left Ventricular Assist Support.

IMPORTANCE: As the Coronavirus disease 2019 (COVID-19) pandemic accelerates, our hospitals have become overwhelmed. OBJECTIVE: To describe detection of COVID-19 in asymptomatic hospitalized individuals awaiting advanced therapies for HF and the management of complications of COVID-19. DESIGN: We present a unique case report of hospital-acquired COVID-19 in a patient on temporary mechanical circulatory support. MAIN OUTCOME: Despite intensive care and monitoring, he developed rapid progression of hypoxic respiratory failure which led to his death. CONCLUSION: This case highlights various considerations for a patient with temporary MCS. It illustrates the high risk for development of COVID-19 for vulnerable hospitalized patients.

Right ventricular outflow tract velocity time integral-to-pulmonary artery systolic pressure ratio: a non-invasive metric of pulmonary arterial compliance differs across the spectrum of pulmonary hypertension.

Pulmonary arterial compliance (PAC), invasively assessed by the ratio of stroke volume to pulmonary arterial (PA) pulse pressure, is a sensitive marker of right ventricular (RV)-PA coupling that differs across the spectrum of pulmonary hypertension (PH) and is predictive of outcomes. We assessed whether the echocardiographically derived ratio of RV outflow tract velocity time integral to PA systolic pressure (RVOT-VTI/PASP) (a) correlates with invasive PAC, (b) discriminates heart failure with preserved ejection-associated PH (HFpEF-PH) from pulmonary arterial hypertension (PAH), and (c) is associated with functional capacity. We performed a retrospective cohort study of patients with PAH (n = 70) and HFpEF-PH (n = 86), which was further dichotomized by diastolic pressure gradient (DPG) into isolated post-capillary PH (DPG < 7 mmHg; Ipc-PH, n = 54), and combined post- and pre-capillary PH (DPG ≥ 7 mm Hg; Cpc-PH, n = 32). Of the 156 patients, 146 had measurable RVOT-VTI or PASP and were included in further analysis. RVOT-VTI/PASP correlated with invasive PAC overall (ρ = 0.61, P < 0.001) and for the PAH (ρ = 0.38, P = 0.002) and HFpEF-PH (ρ = 0.63, P < 0.001) groups individually. RVOT-VTI/PASP differed significantly across the PH spectrum (PAH: 0.13 [0.010-0.25] vs. Cpc-PH: 0.20 [0.12-0.25] vs. Ipc-PH: 0.35 [0.22-0.44]; P < 0.001), distinguished HFpEF-PH from PAH (AUC = 0.72, 95% CI = 0.63-0.81) and Cpc-PH from Ipc-PH (AUC = 0.78, 95% CI = 0.68-0.88), and remained independently predictive of 6-min walk distance after multivariate analysis (standardized ß-coefficient = 27.7, 95% CI = 9.2-46.3; P = 0.004). Echocardiographic RVOT-VTI/PASP is a novel non-invasive metric of PAC that differs across the spectrum of PH. It distinguishes the degree of pre-capillary disease within HFpEF-PH and is predictive of functional capacity.

Cardiopulmonary Exercise Testing-A Valuable Tool, Not Gatekeeper When Referring Patients With Adult Congenital Heart Disease for Transplant Evaluation.

INTRODUCTION: Treatment of patients with adult congenital heart disease (ACHD) with advanced therapies including heart transplant (HT) is often delayed due to paucity of objective prognostic markers for the severity of heart failure (HF). While the utility of Cardiopulmonary Exercise Testing (CPET) in non-ACHD patients has been well-defined as it relates to prognosis, CPET for this purpose in ACHD is still under investigation. METHODS: We performed a retrospective cohort study of 20 consecutive patients with ACHD who underwent HT between March 2010 and February 2016. Only 12 of 20 patients underwent CPET prior to transplantation. Demographics, standard measures of CPET interpretation, and 30-day and 1-year post transplantation outcomes were collected. RESULTS: Patient Characteristics. Twenty patients with ACHD were transplanted at a median of 40 years of age (range: 23-57 years). Of the 12 patients who underwent CPET, 4 had undergone Fontan procedures, 4 had tetralogy of Fallot, 3 had d-transposition of the great arteries, and 1 had Ebstein anomaly. Thirty-day and one-year survival was 100%. All tests included in the analysis had a peak respiratory quotient _1.0. The median peak oxygen consumption per unit time (_VO2) for all diagnoses was 18.2 mL/kg/min (46% predicted), ranging from 12.2 to 22.6. CONCLUSION: There is a paucity of data to support best practices for patients with ACHD requiring transplantation. While it cannot be proven based on available data, it could be inferred that outcomes would have been worse or perhaps life sustaining options unavailable if providers delayed referral because of the lack of attainment of CPET-specific thresholds.

The association between in-hospital hemoglobin changes, cardiovascular events, and mortality in acute decompensated heart failure: Results from the ESCAPE trial.

INTRODUCTION: The effect of acute changes of hemoglobin during index heart failure admission on long-term outcomes remains unknown. METHODS: We examined 433 patients enrolled in the ESCAPE trial. RESULTS: Of the 433 patients, 324 (75%) had baseline and discharge hemoglobin available for analysis. Of those, 64 (20%) had at least 1g/dL drop of hemoglobin by time of discharge. Compared to patients without hemoglobin changes (g/dL), patients with hemoglobin drop were older (59 vs. 55, p=0.011), had lower systolic BP (mmHg) (99 vs. 106, p=0.017), lower sodium (mg/dL) (136 vs. 137 (mg/dL), p=0.025), higher BUN (mg/dL) (37 vs. 26, p<0.001), higher creatinine (mg/dL) (1.6 vs. 1.3, p<0.001) and higher hospital length of stay (10days vs. 6days, p=<0.001). Higher hemoglobin drop was observed in the pulmonary artery catheter (PACs) (vs. clinical care) randomized arm of the trial (2g/dL: 10% versus 3%, p=0.010; 3g/dL: 5% versus 0%, p=0.005). After adjustments, a drop of hemoglobin with at least 1g/dL was associated with increased mortality risk (Adjusted HR 2.38, p=0.003) and higher hemoglobin concentrations by the time of discharge was associated with lower mortality rate (Adjusted HR 0.79, p=0.003). PACs insertion was not associated with adverse clinical outcomes by quartiles of % change of hemoglobin. However, PACs use was an independent predictor of hemoglobin drop during heart failure admission (Adjusted OR: Hb Drop 1g/dL: 1.88, p=0.043; Hb Drop 2g/dL: 3.6 p=0.025). CONCLUSION: In-hospital decrease in hemoglobin is independently associated with increased long-term mortality and hospital length of stay in ADHF. The ideal hemoglobin levels in ADHF patients should be investigated and the insertion of PACs to direct therapy should be weighed against bleeding risks.