In-hospital outcomes with extracorporeal membrane oxygenation alone versus combined with percutaneous left ventricular assist device.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (ECMO) is associated with increased afterload and hindered myocardial recovery. Adding a percutaneous left ventricular assist device (pLVAD) to ECMO is one strategy to unload the left ventricle. We evaluated in-hospital outcomes in cardiogenic shock patients treated with ECMO alone versus ECMO plus pLVAD. METHODS: We conducted a retrospective study using the National Inpatient Sample database from 2011 to 2019. Logistic regression analysis was performed to adjust for covariates. RESULTS: 20,171 patients were included. 16,064 (79.6 %) patients received ECMO alone and 4107 (20.4 %) patients received ECMO plus pLVAD. The ECMO plus pLVAD group had higher rates of mortality, stroke, acute kidney injury, pericardial complications, and vascular complications. After adjusting for covariates, combined therapy was associated with higher rates of mortality (OR 1.2; 95 % CI [1.1-1.3]) and stroke (OR 1.3; 95 % CI [1.2-1.5]), however lower bleeding (OR 0.7; 95 % CI [0.68-0.81]) (p < 0.001 for all). After adjusting for covariates, a subgroup analysis of 5019 patients with acute coronary syndrome cardiogenic shock (ACS-CS) demonstrated higher rates of mortality (OR 1.3; 95 % CI [1.2-1.5]) and stroke (OR 1.7; 95 % CI [1.4-2.1]; p < 0.001 for all) with combined therapy, however similar rates of bleeding compared to ECMO alone (OR 0.95; 95 % CI [0.8-1.1]; p = 0.54). CONCLUSIONS: In the overall group, ECMO plus pLVAD was associated with increased mortality and stroke, however decreased bleeding. In a sub-group of ACS-CS, ECMO plus pLVAD was associated with increased mortality and stroke, however similar rates of bleeding compared to ECMO alone.

Sex Differences in Circulating Biomarkers of Heart Failure.

PURPOSE OF REVSIEW: Evidence is scaling up for sex differences in heart failure; however, clinical relevance of sex-specific differential thresholds for biomarkers is not clearly known. Current ambiguity warrants a further look into the sex-specific studies on cardiac biomarkers and may facilitate understanding of phenotypic presentations, clinical manifestations, and pathophysiologic pathway differences in men and women. RECENT FINDINGS: Recent studies have confirmed the fact that females have differential threshold for biomarkers, with lower troponin and higher NT proBNP levels. Ambiguity continues to exist in the clinical relevance of ST-2, Galectin 3, and other biomarkers. Novel biomarkers, proteomic biomarkers, and circulating micro RNAs with machine learning are actively being explored. Biomarkers in HFpEF patients with higher female representation are evolving. In recent clinical trials, sex-related difference in biomarkers is not seen despite therapeutic intervention being more effective in females compared to males. Sex-related difference exists in the expression of biomarkers in health and in various disease states of heart failure. However, this differentiation has not effectively translated into the clinical practice in terms of diagnostic studies or prognostication. Active exploration to bridge the knowledge gap and novel technologies can shed more light in this area.

Aortic Dissection From an Intra-aortic Balloon Pump: A Dangerous Complication to Keep in Mind.

Despite the benefits of the intra-aortic balloon pump (IABP) being a subject of debate, it remains a widely available and easy-to-use mechanical circulatory support device. Nonetheless, its use is not exempt from complications. Aortic dissection from IABP is an infrequent but deathly complication. We describe a case in which early recognition of the condition led to control through an endovascular approach. A 57-year-old male was admitted for acute decompensated heart failure requiring intravenous inotropic agents. While undergoing assessment for a heart transplant, he developed cardiogenic shock requiring initiation of mechanical circulatory support with an IABP. A few hours after device implantation, the patient developed acute tearing chest pain and was found to have an acute dissection in the descending thoracic aorta. Prompt liaison with the endovascular team led to a thoracic endovascular aortic repair to control the extent of the lesion.

A Pilot Single-Blinded, Randomized, Controlled Trial Comparing BNT162b2 vs. JNJ-78436735 Vaccine as the Third Dose After Two Doses of BNT162b2 Vaccine in Solid Organ Transplant Recipients.

Solid Organ Transplant (SOT) recipients are at significant higher risk for COVID-19 and due to immunosuppressive medication, the immunogenicity after vaccination is suboptimal. In the previous studies, booster method showed significant benefit in this population. In the current study, we compared using a mix-and-match method vs. same vaccine as a third dose in SOT recipients. This was a patient-blinded, single center, randomized controlled trial comparing BNT162b2 vs. JNJ-78436735 vaccine as the third dose after two doses of BNT162b2 vaccine. We included adult SOT recipients with functional graft who had received two doses of BNT162b2 vaccine. Participants were randomly assigned to receive either BNT162b2 or JNJ-78436735 in one-to-one ratio. Primary outcome was SARS-CoV-2 IgG positivity at 1 month after the third dose. Sixty SOT recipients, including 36 kidney, 12 liver, 2 lung, 3 heart, and 5 combined transplants, were enrolled, and 57 recipients were analyzed per protocol. There were no statistically significant differences between the two vaccine protocols for IgG positivity (83.3% vs. 85.2% for BNT162b2 and JNJ-78436735, respectively, p = 0.85, Odds Ratio 0.95, 95% Confidence Interval 0.23-4.00). Comparison of the geometric mean titer demonstrated a higher trend with BNT162b2 (p = 0.09). In this pilot randomized controlled trial comparing mix and match method vs. uniform vaccination in SOT recipients, both vaccines were safely used. Since this was a small sample sized study, there was no statistically significant difference in immunogenicity; though, the mix and match method showed relatively lower geometric mean titer, as compared to uniform vaccine. Further studies need to be conducted to determine duration of this immunogenicity. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT05047640?term=20210641&draw=2&rank=1, identifier 20210641.

Influence of Digital Intervention Messaging on Influenza Vaccination Rates Among Adults With Cardiovascular Disease in the United States: Decentralized Randomized Controlled Trial.

BACKGROUND: Seasonal influenza affects 5% to 15% of Americans annually, resulting in preventable deaths and substantial economic impact. Influenza infection is particularly dangerous for people with cardiovascular disease, who therefore represent a priority group for vaccination campaigns. OBJECTIVE: We aimed to assess the effects of digital intervention messaging on self-reported rates of seasonal influenza vaccination. METHODS: This was a randomized, controlled, single-blind, and decentralized trial conducted at individual locations throughout the United States over the 2020-2021 influenza season. Adults with self-reported cardiovascular disease who were members of the Achievement mobile platform were randomized to receive or not receive a series of 6 patient-centered digital intervention messages promoting influenza vaccination. The primary end point was the between-group difference in self-reported vaccination rates at 6 months after randomization. Secondary outcomes included the levels of engagement with the messages and the relationship between vaccination rates and engagement with the messages. Subgroup analyses examined variation in intervention effects by race. Controlling for randomization group, we examined the impact of other predictors of vaccination status, including cardiovascular condition type, vaccine drivers or barriers, and vaccine knowledge. RESULTS: Of the 49,138 randomized participants, responses on the primary end point were available for 11,237 (22.87%; 5575 in the intervention group and 5662 in the control group) participants. The vaccination rate was significantly higher in the intervention group (3418/5575, 61.31%) than the control group (3355/5662, 59.25%; relative risk 1.03, 95% CI 1.004-1.066; P=.03). Participants who were older, more educated, and White or Asian were more likely to report being vaccinated. The intervention was effective among White participants (P=.004) but not among people of color (P=.42). The vaccination rate was 13 percentage points higher among participants who completed all 6 intervention messages versus none, and at least 2 completed messages appeared to be needed for effectiveness. Participants who reported a diagnosis of COVID-19 were more likely to be vaccinated for influenza regardless of treatment assignment. CONCLUSIONS: This personalized, evidence-based digital intervention was effective in increasing vaccination rates in this population of high-risk people with cardiovascular disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT04584645; https://clinicaltrials.gov/ct2/show/NCT04584645.

Women in mechanical circulatory support: She persisted!

Many women physicians have blazed trails and played instrumental roles in advancing the field of Advanced Heart Failure (AHF), Mechanical Circulatory Support (MCS), and cardiac transplantation to its current recognition and glory. In contrast to other areas of cardiology, women have played an integral role in the evolution and emergence of this sub-specialty. Although the ceiling had been broken much later for women cardiothoracic (CT) surgeons in the field of AHF, the ingress of women into surgical fields particularly CT surgery was stonewalled due to pervasive stereotyping. The constancy, commitment, and contributions of women to the field of AHF and MCS cannot be minimized in bringing this field to the forefront of innovation both from technological aspect as well as in redesigning of healthcare delivery models. Integrated team-based approach is a necessity for the optimal care of MCS patients and forced institutions to develop this approach when patients with durable left ventricular assist devices (LVAD) began discharging from the hospitals to local communities. Women in various roles in this field played a pivotal role in developing and designing patient centered care and coordination of care in a multidisciplinary manner. While embracing the challenges and turning them to opportunities, establishing partnerships and finding solutions with expectations to egalitarianism, women in this field continue to push boundaries and subscribe to the continued evolution of the field of AHF and advanced cardiac therapies.

Restructuring the Heart From Failure to Success: Role of Structural Interventions in the Realm of Heart Failure.

Heart failure through the spectrum of reduced (HFrEF), mid-range (or mildly reduced or HFmEF), and preserved ejection fraction (HFpEF), continues to plague patients' quality of life through recurrent admissions and high mortality rates. Despite tremendous innovation in medical therapy, patients continue to experience refractory congestive symptoms due to adverse left ventricular remodeling, significant functional mitral regurgitation (FMR), and right-sided failure symptoms due to significant functional tricuspid regurgitation (FTR). As most of these patients are surgically challenging for open cardiac surgery, the past decade has seen the development and evolution of different percutaneous structural interventions targeted at improving FMR and FTR. There is renewed interest in the sphere of left ventricular restorative devices to effect reverse remodeling and thereby improve effective stroke volume and patient outcomes. For patients suffering from HFpEF, there is still a paucity of disease-modifying effective medical therapies, and these patients continue to have recurrent heart failure exacerbations due to impaired left ventricular relaxation and high filling pressures. Structural therapies involving the implantation of inter-atrial shunt devices to decrease left atrial pressure and the development of implantable devices in the pulmonary artery for real-time hemodynamic monitoring would help redefine treatment and outcomes for patients with HFpEF. Lastly, there is pre-clinical data supportive of soft robotic cardiac sleeves that serve to improve cardiac function, can assist contraction as well as relaxation of the heart, and have the potential to be customized for each patient. In this review, we focus on the role of structural interventions in heart failure as it stands in current clinical practice, evaluate the evidence amassed so far, and review promising structural therapies that may transform the future of heart failure management.

Effect of Gender on Prognosis in Patients With Takotsubo Syndrome (from a Nationwide Perspective).

Takotsubo syndrome (TTS) largely affects postmenopausal women but has been shown to carry increased mortality risk in men. We sought to evaluate nationwide in-hospital outcomes between men and women admitted with TTS to better characterize these disparities. Using the National Inpatient Sample database from 2011 to 2018, we identified a total of 48,300 hospitalizations with the primary diagnosis of TTS. The primary end point was in-hospital all-cause mortality. Secondary end points included in-hospital complications, length of stay, and discharge disposition. Men with TTS accounted for 8.9% of hospitalizations, were younger in age (62.0 ± 15.1 vs 66.8 ± 12.1 years, p <0.001), and were more frequently Black (9.7% vs 5.8%, p <0.001). Nationwide TTS mortality rates were 1.1% overall and may be improving, but remained higher in men than in women (2.2% vs 1.0%, p <0.001). Male gender was associated with increased all-cause mortality (adjusted odds ratios 2.41, 95% confidence interval 1.88 to 3.10, p <0.001), greater length of stay, and discharge complexity. Men carried increased co-morbidity burden associated with increased cardiogenic shock or mortality, including atrial fibrillation, thrombocytopenia, chronic kidney disease, and chronic obstructive pulmonary disease. Men more frequently developed acute kidney injury, ventricular arrhythmias, cardiac arrest, and respiratory failure. Male gender remains associated with nearly 2.5-fold increase in in-hospital mortality risk. In conclusion, early identification of patients with high-risk co-morbidities and close monitoring for arrhythmias, renal injury, or cardiogenic shock may reduce morbidity and mortality.

Malignancy: An Adverse Effect of Immunosuppression.

Benefits of solid organ transplantation in end stage organ diseases are indisputable. Malignancy is a feared complication of solid organ transplantation and is a leading cause of mortality in patients with organ transplantation. Iatrogenic immunosuppression to prevent graft rejection plays a crucial role in the cancer development in solid organ transplant recipients. Chronic exposure to immunosuppression increases the malignancy burden through deregulation of host immune defense mechanisms and unchecked proliferation of oncogenic viruses and malignancies associated with these viruses. Vigorous screening of candidates undergoing transplant evaluation for malignancies, careful assessment of donors, and vigilant monitoring of transplant recipients are necessary to prevent, detect, and manage this life-threatening complication.

Cefazolin plus ertapenem and heart transplantation as salvage therapy for refractory LVAD infection due to methicillin-susceptible Staphylococcus aureus: A case series.

The use of left ventricular assist devices (LVADs) is increasingly more common as the availability of donor organs in relation to failing hearts is outstandingly limited. Infections are the most common complications in LVAD recipients, particularly those caused by Staphylococcus spp. Refractory LVAD-related infections are not uncommon as achieving adequate source control is often not feasible before heart transplantation. Evidence suggest that cefazolin plus ertapenem is effective in refractory methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, but this approach has not been described in LVAD recipients. In this article, we report two cases of refractory MSSA bacteremia in LVAD recipients that were successfully treated with salvage therapy with cefazolin plus ertapenem and subsequent heart transplantation. This treatment strategy should be considered in patients with refractory LVAD-associated infection due to MSSA that are not responding to standard treatment.

What Is the Status of Regenerative Therapy in Heart Failure?

PURPOSE OF REVIEW: Heart failure remains a major public health concern with high burden of morbidity and mortality despite advances in pharmacotherapy, device therapy, and surgical and percutaneous techniques. Cardiac regeneration may have a role to play in these patients with a huge unmet need for these therapies in patients with chronic ischemic heart disease, post-infarct heart failure, dilated cardiomyopathy, and heart failure with preserved ejection fraction. RECENT FINDINGS: In this review, we focus on the pre-clinical and translational basis for different modes of cardiac regenerative medicine and then critically appraise the clinical evidence amassed from pivotal clinical trials focused on cardiac regeneration for ischemic and non-ischemic cardiomyopathies. Cardiac regenerative medicine is rapidly evolving with novel approaches involving cell-based, cell-free, tissue engineering, and hybrid therapies to achieve myocardial regeneration and repair. Further studies are warranted with a robust comparison arm with optimal contemporary medical therapy to translate regenerative therapies to a clinical reality.

Assessing in-hospital cardiovascular, thrombotic and bleeding outcomes in patients with chronic liver disease undergoing left ventricular assist device implantation.

INTRODUCTION: Chronic liver disease (CLD) and advanced heart failure (HF) often co-exist with coagulopathy and hematologic abnormalities being major concerns in this cohort. Perioperative outcomes of patients undergoing LVAD implantation can be affected by coagulopathy, associated with a higher International Normalized Ratio (INR) and cytopenias, as well as pre-operative use of antiplatelet therapy and systemic anticoagulation. Our study is aimed at evaluating the in-hospital mortality and clinical outcomes of patients with CLD who underwent LVAD implantation compared to patients who underwent LVAD implantation without CLD. METHODS: The National Inpatient Sample Database was queried from 2012 to 2017 for relevant International Classification of Diseases (ICD)-9 and ICD-10 procedural and diagnostic codes. Baseline characteristics and in-hospital outcomes were compared in patients with chronic liver disease and those without, who underwent LVAD implantation. RESULTS: A total of 22,955 patients underwent LVAD implantation, 2200 of which had CLD. There was no difference in mean age between those with and without CLD (52.8 ± 14.2 vs. 55.7 ± 15.4 years old, p < 0.001), and 23.7% of patients were female. The proportion of patients with CLD undergoing LVAD implantation trended downward between 2012 and 2017 (average annual growth rate: "-14.8%"). In-hospital post-LVAD outcomes revealed: all-cause inpatient mortality (14.8% vs. 11.1%), major bleeding (34.3% vs. 30.2%), transfusion of platelets (18.0% vs. 14.0%), subarachnoid hemorrhage (1.6% vs. 0.7%) and hospital length of stay were greater in patients with CLD (p < 0.001 for all values). LVAD thrombosis (6.6% vs. 9.4%) and postoperative ischemic stroke (3.4% vs. 6.1%) occurred less in patients with CLD (p < 0.001 for both). There were no statistically significant differences in occurrence of post-LVAD gastrointestinal bleeding and transfusion of fresh frozen plasma or packed red blood cells (p > 0.05 for all). Using a multivariate logistic regression model to adjust for confounding factors, CLD was predictive of increased in-hospital all-cause mortality in patients undergoing LVAD implantation (adjusted odds ratio: 1.29, 95% confidence interval [CI]; 1.06 to 1.56, p = 0.010). CONCLUSION: LVAD implantation in patients with chronic liver disease was associated with increased mortality and post-LVAD major bleeding with increased utilization of platelet products yet comparable thrombotic complications. Further studies are needed to evaluate the balance and pathophysiology of bleeding risks when compared to thrombosis, as well as predictors in patients with chronic liver disease.

Managing Cardiovascular Risk in the Post Solid Organ Transplant Recipient.

Solid organ transplantation is an effective treatment for patients with end-stage organ disease. The prevalence of cardiovascular diseases (CVD) has increased in recipients. CVD remains a leading cause of mortality among recipients with functioning grafts. The pathophysiology of CVD recipients is a complex interplay between preexisting risk factors, metabolic sequelae of immunosuppressive agents, infection, and rejection. Risk modification must be weighed against the risk of mortality owing to rejection or infection. Aggressive risk stratification and modification before and after transplantation and tailoring immunosuppressive regimens are essential to prevent complications and improve short-term and long-term mortality and graft survival.