Impella 5.5: A Systematic Review of the Current Literature.

OBJECTIVE: Impella 5.5 (Abiomed, Danvers, MA, USA) is a temporary mechanical circulatory support device used for patients in cardiogenic shock. This review provides a comprehensive overview of the device's clinical effectiveness, safety profile, patient outcomes, and relevant procedural considerations. METHODS: We conducted a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the PubMed/MEDLINE database. The search query included articles available from October 6, 2022, through January 13, 2023. Our initial search identified 75 studies. All records were screened by 2 independent reviewers using the Covidence software for adherence to our inclusion criteria, and 8 retrospective cohort studies were identified as appropriate for inclusion. RESULTS: Across the included studies, the sample size ranged from 4 to 275, with predominantly male cohorts. Indications for Impella support varied, and the duration of support ranged from 9.8 to 70 days. Overall, Impella support appeared to be associated with favorable survival rates and manageable complications in various patient populations. Complications associated with Impella use included bleeding, stroke, and device malfunctions. Two studies compared prolonged and Food and Drug Administration-approved Impella support, showing similar outcomes and adverse events. CONCLUSIONS: Impella 5.5 continues to be an attractive option for bridging patients to definitive therapy. Survival during and after Impella 5.5 was favorable for patients regardless of initial indication. However, device use was associated with several important complications, which calls for judicious use and a precontemplated exit strategy. Limitations of this literature review include biases inherent to the retrospective studies included, such as selection and publication bias.

Combination diuretic therapies in heart failure: Insights from GUIDE-IT.

Introduction: Diuretics are the mainstay of maintaining and restoring euvolemia in the management of heart failure. Loop diuretics are often preferred, however, combination diuretic therapy (CDT) with a thiazide diuretic is often used to overcome diuretic resistance and increase diuretic effect. We performed an analysis of the GUIDE-IT study to assess all-cause mortality and time to first hospitalizations in patients necessitating CDT. Methods: Patients from the GUIDE-IT dataset were stratified by their requirement for CDT with a thiazide to achieve euvolemia. A total of 894 patients were analyzed, 733 of which were treated with loop diuretics alone vs 161 used either chlorothiazide or metolazone in addition to loop diuretics. Kaplan-Meir curves were derived with log-rank p-values to evaluate for differences between the groups. Results: There was no significant difference in all-cause mortality regardless of CDT utilization status (mean survival of 612.704 days vs 603.326 days, p = 0.083). On subgroup analysis, there was no significant difference in all-cause mortality amongst those using loop diuretics compared to CDT in the BNP-guided therapy group, (mean survival time 576.385 days vs 620.585 days, p = 0.0523), nor the control group (614.1 days vs 588.9 days; p = 0.5728). Time to first hospitalization was reduced in all using CDT compared to loop diuretics alone (280.5 days vs 407.2 days, p < 0.0001). On subgroup analysis, both the BNP-guided group as well as the control group had reduced time to first hospitalization in the CDT group compared to those who did not require CDT (BNP group: 287.503 days vs 402.475 days, p ≤0.0001; control group 248.698 days vs 399.035 days, p = 0.0009). Conclusion: Use of CDT is associated with earlier time to hospitalization, though no association was identified with increased all-cause mortality. Further prospective studies are likely needed to determine the true risk and benefits of combination diuretic therapy.

Natural recovery of cardiac allograft diastolic function, a retrospective longitudinal report.

Cardiac allografts suffer diastolic dysfunction early post-heart transplantation (HTx) due to ischemic injury, however the natural course of diastology recovery post HTx remains unknown (Tallaj et al., 2007 [1]). We retrospectively reviewed 60 adult HTx patients between 2015 and 2021 at a single site. Invasive hemodynamics and echocardiograms were obtained at 2 weeks and 1, 3, 6, and 12 months post-HTx. RA strain by 2D feature tracking was compared to intracardiac pressure measurements. In all patients, we observed normalization of RV and RA filling pressures by post-operative week 12 and recovery of diastolic dysfunction by month 6. There was an inverse correlation between RV end-diastolic pressure and RA contractile (r = -0.192, p < 0.05) and reservoir (r = -0.128, p < 0.05) functions in the allograft. As the post-transplant care paradigm shifts away from invasive procedures, right atrial indices should be included in imaging-based allograft surveillance studies.

Left ventricular assist device implantation outcomes in patients with subcutaneous implantable cardioverter-defibrillators: A case series.

Background: Left ventricular assist devices (LVADs) may induce electromagnetic interference (EMI) affecting implanted cardiac devices, including more novel subcutaneous implantable cardiac defibrillators (S-ICDs). Methods: In this case series, the authors retrospectively reviewed courses of 6 patients with S-ICDs who underwent LVAD implantation at a single center. Results: Of the 6 patients reviewed, 4 experienced inappropriate ICD shocks, of which 3 resulted from EMI. Five of the 6 patients ultimately had S-ICD therapies disabled. Conclusions: Due to EMI resulting in inappropriate shocks and improved tolerability of malignant arrhythmias, deactivation or removal of S-ICDs should be considered in patients undergoing LVAD implantation.

Temporary mechanical support in the peripartum patient as a bridge to postpartum recovery: A report of three cases.

Cardiogenic shock (CS) is a severe complication of peripartum cardiomyopathy (PPCM). Patients with deteriorating CS often require temporary mechanical circulatory support. In PPCM, this can be used as a bridge to postpartum recovery or bridge to decision. The outcomes are unclear, especially if prolonged utilization is required. We present a case series of three patients with PPCM in deteriorating CS who were successfully supported with a ventricular assist device or veno-arterial extracorporeal membrane oxygenation as a bridge to postpartum recovery.

Novel formylpeptide receptor 1/2 agonist limits hypertension-induced cardiovascular damage.

AIMS: Formylpeptide receptors (FPRs) play a critical role in the regulation of inflammation, an important driver of hypertension-induced end-organ damage. We have previously reported that the biased FPR small-molecule agonist, compound17b (Cmpd17b), is cardioprotective against acute, severe inflammatory insults. Here, we reveal the first compelling evidence of the therapeutic potential of this novel FPR agonist against a longer-term, sustained inflammatory insult, i.e. hypertension-induced end-organ damage. The parallels between the murine and human hypertensive proteome were also investigated. METHODS AND RESULTS: The hypertensive response to angiotensin II (Ang II, 0.7 mg/kg/day, s.c.) was attenuated by Cmpd17b (50 mg/kg/day, i.p.). Impairments in cardiac and vascular function assessed via echocardiography were improved by Cmpd17b in hypertensive mice. This functional improvement was accompanied by reduced cardiac and aortic fibrosis and vascular calcification. Cmpd17b also attenuated Ang II-induced increased cardiac mitochondrial complex 2 respiration. Proteomic profiling of cardiac and aortic tissues and cells, using label-free nano-liquid chromatography with high-sensitivity mass spectrometry, detected and quantified ∼6000 proteins. We report hypertension-impacted protein clusters associated with dysregulation of inflammatory, mitochondrial, and calcium responses, as well as modified networks associated with cardiovascular remodelling, contractility, and structural/cytoskeletal organization. Cmpd17b attenuated hypertension-induced dysregulation of multiple proteins in mice, and of these, ∼110 proteins were identified as similarly dysregulated in humans suffering from adverse aortic remodelling and cardiac hypertrophy. CONCLUSION: We have demonstrated, for the first time, that the FPR agonist Cmpd17b powerfully limits hypertension-induced end-organ damage, consistent with proteome networks, supporting development of pro-resolution FPR-based therapeutics for treatment of systemic hypertension complications.

Outcome of Patients With Systolic Heart Failure Who Underwent Sympathectomy for Ventricular Arrhythmia.

Cardiac sympathetic denervation (CSD) is a surgical procedure increasingly used for managing ventricular arrhythmia refractory to conventional medical therapy. Long-term outcomes of CSD in patients with systolic heart failure has not been well studied. This observational study aimed to evaluate the medical co-morbidities and outcomes of patients with systolic heart failure who underwent CSD performed as treatment for ventricular arrhythmia refractory to conventional therapy. A retrospective analysis in adult patients with ventricular arrhythmia and systolic heart failure who underwent unilateral or bilateral CSD at a single center was performed. Unadjusted Kaplan-Meier survival curves were constructed to evaluate survival after CSD. Between June 1, 2011 and March 31, 2021, 32 adult patients (age 62 ± 11.6 years, 88% male, left ventricular ejection fraction 22% ± 8.2%) with systolic heart failure underwent unilateral left (n = 4), unilateral right (n = 1), or bilateral CSD (n = 27). Mean survival after CSD was 613 ± 745 days, and the mean time from CSD to death was 291 ± 447 days. The cumulative probability of survival 1 year after CSD was 61.4%. In this single-center observational study, CSD performed for refractory ventricular arrhythmia showed favorable survival in patients with systolic heart failure. In conclusion, this study lays the groundwork for a more in-depth analysis of the potential survival benefits of CSD in this patient group.

A new opportunity for patient selection and optimization: Systematic review of cognitive frailty in patients undergoing left ventricular assist device implantation.

The prognostic implication of cognitive frailty assessment in patients undergoing left ventricular assist device (LVAD) implantation remains unclear. We conducted a systematic review to evaluate assessment strategies and their significance for patients undergoing LVAD implantation. A comprehensive search of PubMed, Embase, and the Cumulative Index to Nursing and Allied Health Literature from inception until September 2022 and a review of meeting proceedings were performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies that investigated the prognostic value of cognitive frailty or any related cognition-based assessment in patients undergoing LVAD implantation were included. Study characteristics, patient demographics, and type of cognitive assessment were extracted. Primary outcomes included length of stay, readmissions, and all-cause mortality. Of 664 records retrieved, 12 (4 prospective, 8 retrospective) involving 16 737 subjects (mean age, 56.9 years; 78.3% men) met inclusion criteria; 67% of studies used the Montreal Cognitive Assessment to assess cognitive frailty. Outcomes reported were highly variable, with 42% reporting readmission, 33% reporting LOS, and 83% reporting mortality data; only two studies provided data on all three. Cognitive frailty was associated with prolonged length of stay in 75% of studies reporting this outcome. Only 40% and 60% of studies that reported readmissions and mortality outcomes, respectively, suggested a predictive association. Pre-LVAD cognitive frailty is likely associated with worse outcomes postimplant. However, the heterogenous reporting of outcomes data and lack of consistent definitions in the literature limit its prognostic value. Additional research on markers for cognitive frailty and improved standards of reporting may allow for future analyses and enhance preoperative risk assessment and patient care. Geriatr Gerontol Int 2024; 24: 204-210.

Left Ventricular Assist Device Use in Minorities: An Analysis of the National Inpatient Sample.

Minorities are less likely to receive a left ventricular assist device (LVAD). This, however, is based on total implant data. By examining rates of LVAD implant among patients admitted with heart failure complicated by cardiogenic shock, we sought to further elucidate LVAD utilization rates and racial disparities. Utilizing the National Inpatient Sample from 2013 to 2019, all patients admitted with a primary diagnosis of heart failure complicated by cardiogenic shock were included for analysis. Those who then received an LVAD during that hospitalization defined the LVAD utilization which was examined for any racial disparities. Left ventricular assist device utilization was low across all racial groups with no significant difference noted in univariate analysis. Non-Hispanic Blacks had the highest length of stay (LOS), the highest proportion of discharge to home (71.52%), and the lowest inpatient mortality (6.33%). Multivariable modeling confirmed the relationship between race and LOS; however, no differences were noted in mortality. Non-Hispanic Blacks were found to be less likely to receive an LVAD; however, when controlling for payer, median household income, and comorbidities, this relationship was no longer seen. Left ventricular assist devices remain an underutilized therapy in cardiogenic shock. When using a multivariable model, race does not appear to affect LVAD utilization.

Reconsidering FDA Guidelines: A Single-Center Experience of Prolonged Impella 5.5 Support.

OBJECTIVE: Impella 5.5 (Abiomed, Danvers, MA, USA) is approved by the US Food and Drug Administration (FDA) for mechanical circulatory support for ≤14 days. It is unknown whether prolonged support is associated with worse outcomes. We sought to review our single-center experience with Impella 5.5 and compare outcomes based on support duration. METHODS: We retrospectively reviewed adult patients (≥18 years old) supported with Impella 5.5 at our institution (May 2020 to April 2023). Patients on prolonged support (>14 days) were compared with those supported for ≤14 days. RESULTS: There were 31 patients supported with Impella 5.5 including 14 (45.2%) supported >14 days. Median support duration for those on prolonged support was 43.5 (interquartile range [IQR] 25 to 63.5) days versus 8 (IQR 6, 13) days for those who were not (P < 0.001). Overall, the device-related complication rate was 9.7% and did not differ between groups (P = 0.08). Overall, 30-day postimplant survival was 71% and did not differ by support duration (P = 0.2). In-hospital mortality was 32% and did not differ between cohorts (P > 0.99). Among those surviving to explant (n = 22), long-term strategy included bridge to durable ventricular assist device (18%, n = 4), cardiac transplant (55%, n = 12), and cardiac recovery (27%, n = 6). CONCLUSIONS: High-risk patients with cardiogenic shock may be supported with Impella 5.5 beyond the FDA-approved duration without increased risk of complications or mortality.

Transthyretin Cardiac Amyloidosis Disguised as Light Chain Amyloidosis or Multiple Myeloma?

We describe 2 challenging cases of cardiac transthyretin amyloidosis initially treated as cardiac amyloidosis light chain in the setting of active myeloma. Endomyocardial biopsy with mass spectrometry was essential to confirm the appropriate diagnosis to direct the treatment.

A case of ultra-prolonged intra-aortic balloon pump support via sheathless femoral access.

Background: An intra-aortic balloon pump (IABP) is a mechanical circulatory support platform with a relatively low complication rate. Axillary access is increasingly utilized to allow rehabilitation. Case summary: We present a case of femoral IABP inserted into the femoral artery percutaneously via a sheathless technique that allowed the patient to ambulate and physically rehabilitate over 102 days until cardiac transplantation. The patient was able to progress with the protocolized rehabilitation programme to up to 3500 ft walking distance. The IABP was removed at the time of transplantation without any vascular complications. Discussion: While axillary IABP offers an opportunity to rehabilitate, it has an unacceptably high complication rate, often resulting in vascular injury that adds morbidity to an acutely ill cohort. In this case, we found that sheathless femoral IABP access offered stability for a prolonged time while avoiding pain, bleeding, infection, and vascular injury. We hypothesize that this is due to less indwelling prosthetic material usage and also device flexibility, allowing conformation to the natural course of the femoral artery. We are encouraged by this case to use a sheathless access approach for patients expected to require prolonged IABP support.

Recurrent Cardiac Sarcoidosis and Giant Cell Myocarditis After Heart Transplant: A Case Report and Systematic Literature Review.

Recurrence of cardiac sarcoidosis (CS) and giant cell myocarditis (GCM) after heart transplant is rare, with rates of 5% in CS and 8% in GCM. We aim to identify all reported cases of recurrence in the literature and to assess clinical course, treatments, and outcomes to improve understanding of the conditions. A systematic review, utilizing Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines, was conducted by searching MEDLINE/PubMed and Embase of all available literature describing post-transplant recurrent granulomatous myocarditis, CS, or GCM. Data on demographics, transplant, recurrence, management, and outcomes data were collected from each publication. Comparison between the 2 groups were made using standard statistical approaches. Post-transplant GM recurrence was identified in 39 patients in 33 total publications. Reported cases included 24 GCM, 12 CS, and 3 suspected cases. Case reports were the most frequent form of publication. Mean age of patients experiencing recurrence was 42 years for GCM and 48 years for CS and favored males (62%). Time to recurrence ranged from 2 weeks to 9 years post-transplant, occurring earlier in GCM (mean 1.8 vs 3.0 years). Endomyocardial biopsies (89%) were the most utilized diagnostic method over cardiac magnetic resonance and positron emission tomography. Recurrence treatment regimens involved only steroids in 40% of CS, whereas other immunomodulatory regimens were utilized in 70% of GCM. In conclusion, GCM and CS recurrence after cardiac transplantation holds associated risks including concurrent acute cellular rejection, a higher therapeutic demand for GCM recurrence compared with CS, and mortality. New noninvasive screening techniques may help modify post-transplant monitoring regimens to increase both early detection and treatment of recurrence.

Glycerol 3-phosphate phosphatase/PGPH-2 counters metabolic stress and promotes healthy aging via a glycogen sensing-AMPK-HLH-30-autophagy axis in C. elegans.

Metabolic stress caused by excess nutrients accelerates aging. We recently demonstrated that the newly discovered enzyme glycerol-3-phosphate phosphatase (G3PP; gene Pgp), which operates an evolutionarily conserved glycerol shunt that hydrolyzes glucose-derived glycerol-3-phosphate to glycerol, counters metabolic stress and promotes healthy aging in C. elegans. However, the mechanism whereby G3PP activation extends healthspan and lifespan, particularly under glucotoxicity, remained unknown. Here, we show that the overexpression of the C. elegans G3PP homolog, PGPH-2, decreases fat levels and mimics, in part, the beneficial effects of calorie restriction, particularly in glucotoxicity conditions, without reducing food intake. PGPH-2 overexpression depletes glycogen stores activating AMP-activate protein kinase, which leads to the HLH-30 nuclear translocation and activation of autophagy, promoting healthy aging. Transcriptomics reveal an HLH-30-dependent longevity and catabolic gene expression signature with PGPH-2 overexpression. Thus, G3PP overexpression activates three key longevity factors, AMPK, the TFEB homolog HLH-30, and autophagy, and may be an attractive target for age-related metabolic disorders linked to excess nutrients.

Exploratory structural equation modeling: a streamlined step by step approach using the R Project software.

Confirmatory Factor Analysis (CFA) has been a popular yet limited approach to assessing latent factor structures. Despite items rarely loading exclusively on one latent factor in multifactorial scales, CFA assumes all indicators/items should load uniquely on their allocated latent dimensions. To address this weakness, Exploratory Structural Equation Modeling (ESEM) combines exploratory factor analyses (EFA) and CFA procedures, allowing cross-loadings to occur when assessing hypothesized models. Although such advantages have enhanced ESEM popularity, its adoption is often limited by software rigidity and complex coding difficulties. To address these obstacles, the current tutorial presents a streamlined, step-by-step approach using the open-source software R while providing both R and Mplus ESEM syntax. The tutorial demonstrates the sequence of the ESEM stages by examining the frequently debated Strengths and Difficulties Questionnaire (SDQ) factor structure, using openly accessible data from the Longitudinal Study of Australian Children (LSAC). As ESEM may allow a better understanding of the complex associations in multidimensional scales, this tutorial may optimize the epidemiological and clinical assessment of common yet multifaceted psychiatric presentations.

A combinatorial droplet microfluidic device integrated with mass spectrometry for enzyme screening.

Mass spectrometry (MS) enables detection of different chemical species with a very high specificity; however, it can be limited by its throughput. Integrating MS with microfluidics has a tremendous potential to improve throughput and accelerate biochemical research. In this work, we introduce Drop-NIMS, a combination of a passive droplet loading microfluidic device and a matrix-free MS laser desorption ionization technique called nanostructure-initiator mass spectrometry (NIMS). This platform combines different droplets at random to generate a combinatorial library of enzymatic reactions that are deposited directly on the NIMS surface without requiring additional sample handling. The enzyme reaction products are then detected with MS. Drop-NIMS was used to rapidly screen enzymatic reactions containing low (on the order of nL) volumes of glycoside reactants and glycoside hydrolase enzymes per reaction. MS "barcodes" (small compounds with unique masses) were added to the droplets to identify different combinations of substrates and enzymes created by the device. We assigned xylanase activities to several putative glycoside hydrolases, making them relevant to food and biofuel industrial applications. Overall, Drop-NIMS is simple to fabricate, assemble, and operate and it has potential to be used with many other small molecule metabolites.

Utilization of the percutaneous left ventricular support as bridge to heart transplantation across the United States: In-depth UNOS database analysis.

BACKGROUND: Intra-aortic balloon pump (IABP) and Impella device utilization as a bridge to heart transplantation (HTx) have risen exponentially. We aimed to explore the influence of device selection on HTx outcomes, considering regional practice variation. METHODS: A retrospective longitudinal study was performed on a United Network for Organ Sharing (UNOS) registry dataset. We included adult patients listed for HTx between October 2018 and April 2022 as status 2, as justified by requiring IABP or Impella support. The primary end-point was successful bridging to HTx as status 2. RESULTS: Of 32,806 HTx during the study period, 4178 met inclusion criteria (Impella n = 650, IABP n = 3528). Waitlist mortality increased from a nadir of 16 (in 2019) to a peak of 36 (in 2022) per thousand status 2 listed patients. Impella annual use increased from 8% in 2019 to 19% in 2021. Compared to IABP, Impella patients demonstrated higher medical acuity and lower success rate of transplantation as status 2 (92.1% vs 88.9%, p < 0.001). The IABP:Impella utilization ratio varied widely between regions, ranging from 1.77 to 21.31, with high Impella use in Southern and Western states. However, this difference was not justified by medical acuity, regional transplant volume, or waitlist time and did not correlate with waitlist mortality. CONCLUSIONS: The shift in utilizing Impella as opposed to IABP did not improve waitlist outcomes. Our results suggest that clinical practice patterns beyond mere device selection determine successful bridging to HTx. There is a critical need for objective evidence to guide tMCS utilization and a paradigm shift in the UNOS allocation system to achieve equitable HTx practice across the United States.

Pharmacological Therapy Optimization for Heart Failure: A Practical Guide for the Internist.

Heart failure carries significant morbidity and mortality and affects a large population of patients cared for predominantly by primary care physicians. The complexity of managing heart failure patients is increasing as new therapies continue to emerge. This review outlines important clinical pearls and proposes strategies for optimization of medical therapy.

Amyloid transthyretin cardiac amyloidosis with different manifestations, test findings and types.

Amyloid transthyretin amyloidosis usually presents with cardiac amyloidosis manifestations, most commonly with a heart failure syndrome. The history and physical examination offer clues of other cardiac and extracardiac manifestations. Taking a detailed history is essential in elucidating pertinent family and medical history that may increase suspicion for amyloidosis. Further, certain findings on electrocardiogram and imaging should raise suspicion and trigger further workup that can confirm the diagnosis, since treatment is evolving.