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Abstract Background Patients with end-stage heart failure and chronic kidney disease requiring dual-organ transplantation (DOT) face significant challenges in utilizing durable mechanical circulatory support due to the risks associated with renal replacement therapies (RRTs) and multi-organ failure. Given the limited options available for long-term support in this patient population, there remains a critical need for alternative strategies to optimize end-organ function and bridge patients safely to transplant. With prolonged waitlist times for DOT, we present our experience with the Impella 5.5 as temporary mechanical circulatory support, demonstrating its potential to provide hemodynamic stability and support as a bridge to transplantation (BTT) in this complex cohort. Methods A single-centre retrospective review was completed of all patients listed for single-organ transplantation or DOT between December 2019 and November 2022 at Mayo Clinic in Florida, supported by the Impella 5.5 intended as BTT. The focus of this analysis was patients requiring RRT or listed for heart/kidney transplantation. Data were extracted from the electronic health record at baseline and during their transplant episode of care after institutional review board approval as exempt status for retrospective data collection. Results A total of 41 patients were supported with Impella 5.5, intended as BTT. All patients underwent successful transplantation. We focus on the 10 patients with Impella support who underwent DOT. In the DOT group, the median age at transplantation was 63 years (59–66), with nine males and one female. The baseline median ejection fraction was 19% (15–22), with 50% Caucasian and 50% African American and an even split between ischaemic and non-ischaemic aetiology. Median body mass index was 30 kg/m2 (26–31), and 60% were in blood group O. The median time on the waitlist for DOT patients was 53 days (29–75). Perioperative management of DOT Impella patients demonstrated baseline haemodynamics of RA 11 mmHg (7–16), mean PA 36 mmHg (32–47), PCWP 29 mmHg (21–35), mixed venous saturation (SVO2%) 51 (46–61) and Fick CI 2.03 L/min/m2 (1.66–2.5). Post-Impella placement haemodynamics demonstrated significant improvements in RA pressure to 5 mmHg (4–8), P = 0.02, SVO2 to 70% (65–72), P = 0.002, and Fick CI to 5.5 (5.2–8), P = 0.03. The average duration of support was 44 days (range 10–94). The median glomerular filtration rate at baseline was 27 mmol/L (16–29). Twenty-four hour urine protein averaged 168 mg/24 h (range 87–328), with the 24 h creatinine clearance of 29 mg/24 h (range 24–35). Eight of the 10 patients required continuous or intermittent RRT before DOT. The median total duration of RRT (including Impella support) was 36 days (9–72). DOT recipients had a 1 year survival of 90%, with an average follow-up of 432 days. Conclusions Our findings demonstrate that prolonged use of the Impella 5.5 provides safe and effective haemodynamic support for patients with end-stage heart and kidney failure awaiting dual-organ transplantation. With a 1 year survival rate of 90%, our data suggest that Impella 5.5 can be a viable alternative to traditional support strategies, particularly in patients who are otherwise limited by RRTs. As dual-organ transplantation becomes more prevalent, the Impella 5.5 offers a promising bridge to transplant, improving both short-term and long-term outcomes in this complex patient population.

Introduction: Takotsubo cardiomyopathy (TCM), also known as stress cardiomyopathy or Broken Heart Syndrome, is a reversible, transient state of myocardial dyskinesis and apical ballooning. Infrequently, TCM may progress to severe life-threatening complications such as cardiogenic shock. Early mechanical circulatory support (MCS) is crucial to myocardial recovery in these cases. We present one of the first cases of TCM successfully treated with the advanced micro-axial minimally invasive Impella 5.5 with SmartAssist MCS device. Case Presentation: A female in her late 70s with a history of hypothyroidism, atrial fibrillation post-ablation, and cholelithiasis was referred to our facility for an elective cholecystectomy. Post-anesthesia induction with propofol 2.1 mg/kg (140 mg bolus), she became bradycardic and hypotensive, eventually leading to asystole, requiring CPR and termination of the procedure. Echocardiography revealed a left ventricular ejection fraction (LVEF) of 24% with mid-ventricular akinesis and apical ballooning with mild mitral regurgitation, suggesting the diagnosis of TCM. Cardiac catheterization showed RA 20 and mean PA 42 mmHg. Lactate was 18.7 mmol/L and LDH 1776 U/L, suggesting progressive shock. Continuous epinephrine 0.1 mcg/kg/min and norepinephrine 0.06 mcg/kg/min were titrated for BP 97/58, and she was initially supported with the Impella CP device. Despite aggressive efforts, rising LDH levels and increased vasopressor needs indicated inadequate organ perfusion, requiring an upgrade to Impella 5.5. Impella 5.5 support for 11 days led to impressive myocardial recovery, leading to reductions, and eventual discontinuation, of inotropes and vasopressors. Post-Impella 5.5 explantation, her LVEF was 59–65% and she was discharged with Mobile Cardiac Outpatient Telemetry (MCOT) monitoring for her arrhythmias and reinitiation of guideline-directed medical therapies (GDMTs) for her comorbidities. Her 2-month follow-up shows sustained LVEF greater than 45% with functional improvements. Conclusions: Early escalation within 24 h of Impella CP to Impella 5.5 provided stabilization of cardiometabolic shock, preventing end-organ damage, allowing recovery of native heart function while maintaining ambulatory status, and allowing for optimizing medical therapy. It presents a safe, minimally invasive, and cost-effective intervention in TCM cases refractory to GDMT or when additional time is needed for decision-making in cases presenting with CS.

Background: Patients with end-stage heart failure-related cardiogenic shock (HF-CS) are conclusively associated with a poor health-related quality of life (HRQL). Axillary mechanical circulatory support (aMCS), such as the Impella 5.5, is increasingly used in this population and may improve HRQL during hospitalization by providing enhanced left ventricular unloading. We aimed to assess changes in HRQL between admission and two weeks after Impella 5.5 placement in patients with HF-CS, using the Kansas City Cardiomyopathy Questionnaire (KCCQ). Methods: We conducted a prospective longitudinal analysis on patients with the Impella 5.5 between May 2023 and July 2023. Participants completed the condensed KCCQ-12 at admission and again two weeks post-implantation. Changes in the scores were evaluated using the Wilcoxon signed-rank test. Results: Fifteen patients were enrolled. The median age was 59 years (50–63), and the median ejection fraction at implantation was 20% (15–30). On admission, most patients reported an overall HRQL of poor-to-fair (46.7%) according to the summary KCCQ-12 score. The median overall summary score increased significantly after Impella 5.5 support (50.52 vs. 28.13, p = 0.005). Symptom frequency (70.83 vs. 43.75, p = 0.009) and quality-of-life (50.00 vs. 12.50, p = 0.023) domains improved significantly, while physical limitation showed a positive trend and social limitation remained unchanged. These HRQL improvements occurred alongside a significant shift toward lower SCAI shock stages, marked increases in cardiac output and cardiac index, and no escalation in vasoactive-inotropic requirements. Conclusions: Impella 5.5 support in HF-CS patients was associated with early and clinically meaningful improvements in HRQL, particularly in symptom frequency and quality of life, during the critical pre-transplant or recovery period. These findings suggest that the Impella 5.5 may provide both physiological and patient-perceived benefits in this high-risk population.

The use of temporary mechanical circulatory support in refractory heart failure cardiogenic shock (HFCS) has risen, leading to potential complications. Post-Cardiac Injury Syndrome (PCIS) from Impella insertion is rare but may result from subclavian artery manipulation and aortic irritation. We report the first case of pericarditis (PCIS) caused by Impella 5.5 insertion in an HFCS patient awaiting heart transplantation. The patient developed chest pain, tachycardia, and hypotension post-Impella insertion. Laboratory results and electrocardiograms confirmed PCIS. Treatment with Ibuprofen and Colchicine was successful. He received a heart transplant 14 days later. This case emphasizes recognizing iatrogenic pericarditis after Impella insertion and the need to avoid additional myocardial strain.

Klippel–Trenaunay (KT) syndrome and Cardiac Sarcoidosis (CS) are two distinct medical conditions that rarely coexist, each presenting unique challenges in diagnosis and management. Here, we present a rare case of a 30-year-old male with a history of KT syndrome complicated by recurrent deep vein thrombosis, who presented with symptoms of acute heart failure including shortness of breath, fatigue, dizziness, palpitations, and chest pain and was subsequently diagnosed with isolated CS. We discuss the importance of thorough clinical evaluation and multimodal diagnostic approaches in this complex scenario with overlapping symptoms and diagnostic dilemmas.

Abstract This study explores parallels between systemic hypoxia adaptation in high-altitude populations and tumorigenesis. We identified EPAS1, a gene critical for hypoxia adaptation in populations such as Tibetans and Sherpas, as playing a similar adaptive role in tumors arising under hypoxic conditions. Tumors from patients with chronic hypoxia displayed impaired DNA repair and frequent emergence of EPAS1 variants, with frequencies reaching up to 90%, echoing the positive selection seen in high-altitude dwellers. Mechanistically, EPAS1 gain-of-function mutations promote COX4I2 expression, reducing cellular oxygen consumption and supporting tumor proliferation in hypoxia. Analysis of clinical data from patients with hypoxia revealed tissue-specific and time-sensitive tumorigenic effects, particularly impacting oxygen-sensitive cells in the postnatal period. Our findings suggest that EPAS1-driven adaptation mechanisms in high-altitude populations provide a model for understanding tumor evolution under hypoxic stress, highlighting how genetic adaptations to diverse stressors in natural populations may yield insights into tumorigenesis and cancer progression. Significance: This study reveals a broad convergence in genetic adaptation to hypoxia between natural populations and tumors, suggesting that insights from natural populations could enhance our understanding of cancer biology and identify novel therapeutic targets. See related commentary by Lee, p. 875

Abstract Clostridiodes difficile’s epidemiology has evolved over the past decades, being recognized as an important cause of disease in the community setting. Even so, there has been heterogeneity in the reports of CA-CDI. Therefore, the aim of this study was to assess the epidemiologic profile of CA-CDI. This systematic review and meta-analysis were conducted according to PRISMA checklist and Cochrane guidelines (CRD42023451134). Literature search was performed by an experienced librarian from inception to April 2023, searching in databases like MEDLINE, Scopus, Web of Science, EMBASE, CCRCC, CDSR, and ClinicalTrials. Observational studies that reported prevalence, incidence of CA-CDI, or indicators to calculate them were included. Pool analysis was performed using a binomial-normal model via the generalized linear mixed model. Subgroup analysis and publication bias were also explored. A total of 49 articles were included, obtaining a prevalence of 5% (95% CI 3–8) and an incidence of 7.53 patients (95% CI 4.45–12.74) per 100,000 person-years. In conclusion, this meta-analysis underscores that among the included studies, the prevalence of CA-CDI stands at 5%, with an incidence rate of 7.3 cases per 100,000 person-years. Noteworthy risk factors identified include prior antibiotic exposure and age.

A BSTRACT Purpose/Background: To identify the proportion of patients with prediabetes who have prescribed metformin and factors related to doing so as a preventive measure for diabetes in primary care at a Family Medicine Unit in northeastern Mexico. Methods: This retrospective observational study included 372 adults who met the criteria for prediabetes diagnosis according to the American Diabetes Association. Data was collected from medical records from January 2020 to December 2021. Possible associations between the variables of interest and the prescription of metformin were tested via hypothesis tests, furthermore, binary logistic regression was performed. Results: Nearly 85% of the patients met at least one criterion for receiving metformin according to ADA recommendations, but only 60% of them were prescribed this medication. Patients with metformin prescriptions differed from those without in aspects such as having a documented diagnosis of prediabetes in their medical records, a higher BMI, and higher glucose levels. Conclusions: Almost one out of two patients with a high risk of type 2 diabetes are not treated with metformin as a preventive measure. Factors associated with metformin prescription included a high BMI, elevated baseline glucose levels, and a prediabetes diagnosis in the medical record. These findings suggest the need for studies to evaluate physicians’ reasons for different treatments and implementation of recommendations for type 2 diabetes prevention in patients with prediabetes in primary health care.

Background: The Society for Cardiovascular Angiography and Interventions (SCAI) staging system is a crucial tool for categorizing cardiogenic shock (CS) and guiding interventions. SCAI staging is traditionally static and may not capture dynamic changes. We evaluated the impact of axillary mechanical circulatory support and SCAI stage transition in patients with CS supported until heart transplantation. Methods: A retrospective study was conducted on patients with Impella support as bridge to transplant. Hemodynamic and vasoactive support parameters were collected and SCAI stage recorded at baseline and after 72 hours. Results: 36 patients were included in the analysis. The median age was 61 (52 – 68) with an EF of 19% (15-26%) (Figure 1). Before Impella placement, the distribution of patients across SCAI stages was as follows: 19 patients in SCAI B, 8 patients in SCAI C, and 9 patients in SCAI D. After 72 hours of Impella support, 7 patients initially classified as SCAI C transitioned to SCAI B with one deteriorating to SCAI D (Figure 2). Patients in SCAI D showed notable improvement, with 8 out of 9 patients transitioning to SCAI B. For patients initially SCAI B, RA changed from 10 to 11 mmHg, and PCWP decreased from 23 to 17 mmHg. The Fick CI increased from 2.53 to 3.02 L/min/m 2 (p=0.04), and the vasoactive inotropic score (VIS) decreased from 7.5-5.0 (p=0.05). In patients initially classified as SCAI C, RA pressure decreased from 13 to 8 mmHg, and PCWP reduced from 32 to 30 mmHg. The Fick CI improved from 1.79 to 2.61 L/min/m 2 (p<0.001), while the VIS decreased from 9.2 to 6.3 (p=0.004). For those initially in SCAI D, RA pressure reduced from 8 to 5 mmHg, and PCWP decreased from 27 to 18 mmHg. The Fick CI increased from 1.55 to 2.67 L/min/m 2 (p=0.002), and the VIS was notably reduced from 4.75 to 3.8 (p=0.36). All 36 patients survived to heart transplantation without major pre-transplant complications. Conclusion: SCAI stage C-E mortality ranges from 25 – 50% or worse. Implementing Impella 5.5 support reduced SCAI severity and may be associated with improved survival in HFCS. We demonstrated lower VIS after Impella 5.5 and a 100% event free survival to heart transplantation despite a 25% baseline SCAI D cohort. Larger data should be evaluated to assess this trend.