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The limitations of the explanatory clinical trial framework include the high expense of implementing explanatory trials, restrictive entry criteria for participants, and redundant logistical processes. These limitations can result in slow evidence generation that is not responsive to population health needs, yielding evidence that is not generalizable. Clinically integrated trials, which integrate clinical research into routine care, represent a potential solution to this challenge and an opportunity to support learning health systems. The operational and design features of clinically integrated trials include a focused scope, simplicity in design and requirements, the leveraging of existing data structures, and patient participation in the entire trial process. These features are designed to minimize barriers to participation and trial execution and reduce additional research burdens for participants and clinicians alike. Broad adoption and scalability of clinically integrated trials are dependent, in part, on continuing regulatory, healthcare system, and payer support. This analysis presents a framework of the strengths and challenges of clinically integrated trials and is based on a multidisciplinary expert "Think Tank" panel discussion that included representatives from patient populations, academia, non-profit funding agencies, the U.S. Food and Drug Administration, and industry. [ABSTRACT FROM AUTHOR]

Background: We aimed to evaluate the influence of heart failure (HF) on clinical and economic outcomes among older adults ≥75 years of age during their acute myocardial infarction (AMI) admission in large population-based study from the United States. We also evaluated the clinical characteristics associated with the presence of HF and the predictors of mortality, healthcare utilization, and cost among older adults with AMI.Methods: From January 1, 2000, to December 31, 2016, AMI admission was identified using the primary diagnosis and concomitant HF was identified using any non-primary diagnoses in the Premier Healthcare Database.Results: Of the 468,654 patients examined, 42,946 (9%) had concomitant HF during their AMI admission. These patients were older, more often female, and were more likely to be White. Patients with concomitant HF were more likely to be frail than non-HF patients (59% vs 15%, P < .001). The mean (SD) Elixhauser comorbidity index was 2.6 (2.5) vs 0.4 (1.1), P < .001 in the AMI with HF vs AMI only group. The use of percutaneous coronary intervention in those with AMI and HF was lower than those with AMI only (15% vs 31%, P < .001). The overall mortality rate for those with HF was 12%, the median [IQR] hospital length of stay was 5 [3,9] days, and only 25% of patients were discharged home. A higher proportion of patients were discharged to rehabilitation or hospice if they had AMI and HF (Rehabilitation: 33% vs 20%, P < .001; Hospice: 5% vs 3%, P < .001). The mean unadjusted cost of an AMI hospitalization in patients with concomitant HF was lower ($12,411 ± $14,860) than in those without HF ($15,828 ± $19,330). After adjusting for age, gender, race, hypertension, frailty, revascularization strategy, and death, the average cost of hospitalization attributed to concomitant HF was +$1,075 (95% CI +876 to $1,274) when compared to AMI patients without HF.Conclusion: In patients ≥75 years of age, AMI with concomitant HF carries higher risk of death, but at ages ≥85 years, the risk difference diminishes due to other competing risks. HF was also associated with longer hospital length of stay and higher likelihood of referral to hospice and rehabilitation facilities when compared to older patients without HF. Care for these older adults is associated with increased hospitalization costs. Measures to identify HF in older adults during their AMI admission are necessary to optimize health outcomes, care delivery, and costs. [ABSTRACT FROM AUTHOR]

Background: After the implementation of the 2018 US heart transplant allocation system, the experience and perceptions of heart transplant clinicians have not been well-cataloged.Methods and Results: This web-based survey of both heart failure cardiologists and surgeons examined physician perspectives about the policy changes and whether the system is meeting its intended goals. The majority of participants (94%, n = 113) responded that the 2018 heart allocation system requires modification. Eighty-four percent reported using more temporary mechanical circulatory support to achieve higher status and 86% were concerned about the change in physician behavior and practices under the new system.Conclusions: Suggestions for possible improvement included higher status for patients on durable left ventricular assist device support, changes to criteria for status 2, modification of status exceptions, and advocacy for a heart allocation score. [ABSTRACT FROM AUTHOR]

Background: Outpatient calcitrope infusions-that is, the cardiac inotropes milrinone and dobutamine-are often used for bridge to transplantation and palliation in advanced heart failure, but few data exist about the real-world use of these agents.Methods and Results: We used the Symphony Integrated DataVerse of commercial, managed Medicare, and Medicaid insurance claims of approximately 280 million people (2012-2020) to determine the incidence and characteristics of ambulatory calcitrope use. Demographics were calculated, including geographic densities at the metropolitan statistical area level. A population projection normalized for age, sex, and location was extrapolated to the total US population. Ambulatory dispensing of milrinone was found in 10,533 outpatients, 1867 in 2019. Ambulatory dobutamine use was found in 4967 outpatients, 836 in 2019. The 2019 total US projection was 3411 for milrinone and 1281 for dobutamine. The mean age was 62 years for milrinone and 68 for dobutamine. Males represented 70% of use. There were differences between drugs in geographic distribution, with more milrinone use in the Northeast and South and more dobutamine use in the Midwest. Duration of use was 4.6 ± 7.2 months for milrinone and 1.8 ± 4.0 months for dobutamine. Of the patients receiving milrinone, 30.6% subsequently underwent cardiac transplantation or left ventricular assist device placement, whereas 10% receiving dobutamine went on to advanced therapies. Less than 0.5% of patients received calcitropes while enrolled in hospice care.Conclusions: More than 4000 patients receive outpatient infusion of calcitropes annually in the outpatient setting. Men are much more likely to receive these medications. A minority of the use is as a bridge to advanced therapies. Geographic variability in use suggests better evidence and consistent guidelines may be helpful. [ABSTRACT FROM AUTHOR]

The coronavirus disease-2019 (COVID-19) pandemic has profoundly changed clinical care and research, including the conduct of clinical trials, and the clinical research ecosystem will need to adapt to this transformed environment. The Heart Failure Academic Research Consortium is a partnership between the Heart Failure Collaboratory and the Academic Research Consortium, composed of academic investigators from the United States and Europe, patients, the U.S. Food and Drug Administration, the National Institutes of Health, and industry members. A series of meetings were convened to address the challenges caused by the COVID-19 pandemic, review options for maintaining or altering best practices, and establish key recommendations for the conduct and analysis of clinical trials for cardiovascular disease and heart failure. This paper summarizes the discussions and expert consensus recommendations. [ABSTRACT FROM AUTHOR]

Background: The effect of secondhand tobacco smoke (SHS) exposure on patients with heart failure (HF) is uncertain. We investigated the association of mortality with SHS exposure for patients with HF.Methods: Nonsmokers with clinical HF were enrolled from 2003 to 2008 in a single-center longitudinal cohort study. The effect of SHS exposure determined by high-sensitivity urinary cotinine on mortality was estimated by multivariable proportional hazards modeling.Results: Mortality was assessed after median 4.3 years. Of 202 patients, enrollment urinary cotinine levels were below the limit of detection for 106 (52%) considered unexposed to SHS. The median detectable cotinine was 0.47 ng/mL (interquartile range: [0.28, 1.28]). Participants were 41% female, 65 ± 17 years old, and 57% white race. Elevated cotinine was associated with increased mortality after multivariate adjustment: hazard ratio (HR) per 1 ng/mL increase in urinary cotinine: 1.15, 95% confidence interval (CI): 1.08-1.23, P < .001. Higher age (HR per 5-year increase: 1.32, 95% CI: 1.22-1.43, P < .001), male sex (HR vs female: 1.52, 95% CI: 1.02-2.28, P = .040), and New York Heart Association class (HR for class III vs I: 2.91, 95% CI: 1.71-4.99, P < .001) were also associated with mortality.Conclusions: SHS exposure is associated with a dose-dependent increase in mortality for patients with HF. [ABSTRACT FROM AUTHOR]

Background: Under-reporting of clinical trial results inhibits dissemination of knowledge, limits understanding of therapeutic interventions, and may ultimately harm patients.Objectives: This study examined the rates and predictors of heart failure clinical trial publication and how they have changed over time.Methods: This study assessed cross-sectional analysis of all heart failure clinical trials registered on ClinicalTrials.gov with at least 2 years follow-up after trial completion. The content area was chosen for the robust clinical trial activity in the field. The primary outcome was manuscript publication with multivariable proportional hazards adjustment to identify associations with publication.Results: Of the 1,429 included studies, 806 (56%) were published as manuscripts, 623 were unpublished, and 97 (7%) reported results without manuscript publication. Of the total, 1,243 were completed after 2007, when the mean 1-year publication rate for interventional trials rose from 12.7% to 19.6% (p = 0.049), which was possibly associated with changes in government regulation. However, there was no further sustained improvement over time, and there was no multivariable association between later completion dates and reporting or publication of results. Funding from the National Institutes of Health and use of clinical (death, hospitalization, myocardial infarction, changes in functional classification) rather than nonclinical primary endpoints were associated with earlier publication. Whether the results were consistent with the primary study hypothesis was not associated with likelihood of publication.Conclusions: The rates of heart failure clinical trial publication or reporting of results remain unacceptably low. Additional efforts by all stakeholders, including investigators, sponsors, regulators, societies, editors, and journals are needed to improve data dissemination. [ABSTRACT FROM AUTHOR]

The term "inotrope" is familiar and intimately connected with pharmaceuticals clinically used for treatment of low cardiac output with cardiogenic shock. Traditional inotropic agents exert their effect by modulating calcium signaling in the myocardium. Their use is associated with poor long-term outcomes. Newer molecules in development intend to break from calcium mediation and the associated detrimental long-term effects by targeting distinct mechanisms of action to improve cardiac performance. Thus, "inotropy" does not sufficiently describe the range of potential novel pharmaceutical products. To enhance communication around and evaluation of current, emerging, and potential therapies, this review proposes a novel nuanced and holistic framework to categorize pharmacological agents that improve myocardial performance based on 3 myocardial mechanisms: calcitropes, which alter intracellular calcium concentrations; myotropes, which affect the molecular motor and scaffolding; and mitotropes, which influence energetics. Novel chemical entities can easily be incorporated into this structure, distinguishing themselves based on their mechanisms and clinical outcomes. [ABSTRACT FROM AUTHOR]

The current heart failure clinical trial environment is strained by increasing complexity and cost, regulatory requirements, competing demands on stakeholders, implementation challenges, and decreasing patient and investigator participation. To begin the process of developing potentially effective strategies and tactics, stakeholders including patients; investigators; academic leaders; pharmaceutical and device industry representatives; society representatives; third-party payers; and government representatives from the U.S. Food and Drug Administration, National Institutes of Health, and Centers for Medicare and Medicaid Services convened in March of 2017. This paper summarizes the discussions, outlines current challenges and actionable opportunities, and makes targeted recommendations to achieve the goals of improving efficiency in clinical trials and speeding the development of effective heart failure therapies, including the formation of an organized Heart Failure Collaboratory. [ABSTRACT FROM AUTHOR]

Atrial fibrillation is the most common cardiac arrhythmia and is associated with significant morbidity, mortality, and economic cost. Although the benefit of anticoagulation has been well described, control of the underlying rhythm disturbance can be achieved in various ways. Numerous therapeutic options exist and continue to be developed; however, the single best strategy has not been elucidated, and rate or rhythm controlling strategies may both be undertaken. The selection of particular agents to successfully achieve these strategies takes into account patient preference and comorbidity, as well as the efficacy and side effect profiles of the possible medications. This review discusses the evidence behind the various agents typically used to treat atrial fibrillation as well as provides a framework on which to make clinical decisions while initiating and continuing therapy. [ABSTRACT FROM AUTHOR]

Although significant cardiac structural and functional improvement is a prerequisite for an LVAD-supported patient to be considered for device weaning, multiple factors including patient willingness, physician expertise, and center experience, weigh in on this complex decision. Existing predictive models defining cardiac recovery as device removal might underestimate the reverse remodeling rates. To develop a predictive tool to identify patients prone to improve cardiac structure and function, independent of the complex decision to deactivate a durable, surgically deployed device. Advanced chronic HF patients (N=703) requiring continuous-flow LVADs were evaluated. After excluding patients with acute HF etiologies and/or inadequate post-LVAD follow-up (<3 months), 3 US programs contributed 390 patients (derivation cohort), while 5 US programs formed the validation cohort (n=245). We defined responders as patients with an LVEF ≥40% and LVEDD ≤6.0 cm within the first year of LVAD support. Multivariable logistic regression on the derivation set yielded a predictive model, which was externally tested; a predictive score was developed. Overall, 18.5% of the patients were responders. Compared to the validation, patients in the derivation cohort were more likely white (83 vs 69%; p<0.001), with ischemic HF (42 vs 33%; p=0.04), and longer HF duration (88 vs 66 months; p<0.001). Multivariable predictors of responders and the derived scoring system are shown in the Figure (c-statistic 0.74 [95% CI: 0.66-0.83] and 0.71 [95% CI: 0.59-0.77] in the derivation and validation set). Focused on patients experiencing significant reverse remodeling post-LVAD support we developed a predictive score achieving good discriminative performance in distinct, heterogeneous, contemporary cohorts. This tool can be useful in selecting patients to implement diagnostic and therapeutic protocols to promote reverse remodeling and myocardial recovery. [ABSTRACT FROM AUTHOR]

Randomized clinical trials are the gold standard for establishing the efficacy and safety of cardiovascular therapies. However, current pivotal trials are expensive, lengthy, and insufficiently diverse. Emerging artificial intelligence (AI) technologies can potentially automate and streamline clinical trial operations. This review describes opportunities to integrate AI throughout a trial's life cycle, including designing the trial, identifying eligible patients, obtaining informed consent, ascertaining physiological and clinical event outcomes, interpreting imaging, and analyzing or disseminating the results. Nevertheless, AI poses risks, including generating inaccurate results, amplifying biases against underrepresented groups, and violating patient privacy. Medical journals and regulators are developing new frameworks to evaluate AI research tools and the data they generate. Given the high-stakes role of randomized trials in medical decision making, AI must be integrated carefully and transparently to protect the validity of trial results. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the influence of age on clinical and economic outcomes in patients ≥75 years of age hospitalized for acute systolic heart failure (AHF). From July 2017 to July 2017, among older adults ≥75 years of age, AHF visits were identified by the ICD-10 systolic heart failure code as any primary or secondary diagnosis in the Premier Healthcare Database, stratified by <75 years vs ≥75 years of age. Of 420,642 visits for AHF, 151,045 (36%) were for patients ≥75 years of age. Of these, 88,138 (58%) were male, 14,846 (10%) were Black, and 9,048 (6%) were Hispanic. The overall inpatient death rate was higher in older than younger patients (Death: 5.49% vs. 3.44%, p <0.001), but among patients ≥75 years, the mortality rate was consistently higher in males than females (Figure). The length of stay was greater among older patients (days: 4 vs. 3, p <0.001), and healthcare costs per visit was higher among older adults ($7,895 vs. $7,775, p<0.001). In the U.S., in-hospital mortality attributed to AHF is highest among older male patients and accounts for significant societal healthcare cost. Methods to risk-stratify older patients presenting with AHF are needed to optimize healthcare delivery and utilization. [ABSTRACT FROM AUTHOR]

We examined the disposition status and healthcare cost among older patients ≥75 years of age hospitalized with acute systolic heart failure (AHF). From July 2017 to July 2018, AHF visits were identified by the ICD-10 systolic heart failure code as any primary or secondary diagnosis among adults ≥75 years-old in the Premier Healthcare Database. Of 377,063 unique patients with AHF, 135,539 (36%) were ≥75 years-old. Of those, 78,550 (58%) were male, 13,247 (10%) were African American, and 9,048 (6%) were Hispanic. The overall unadjusted in-hospital mortality among adults ≥75 years-old was 5.88%; which did not differ by gender. The median length of stay was 4 days and the median healthcare cost attributed to AHF was $8,456 (IQR: $13,221), which did not differ by gender. While older men were more likely to be discharged to rehabilitation or long-term care facility as compared to older women, this difference did not persist after 83 years of age (Figure). With rising cost of care and resource utilization for AHF admissions, understanding reasons behind the differential utilization of rehabilitation and long-term facilities among older patients may be critical to optimize healthcare delivery and reduce readmission rates. [ABSTRACT FROM AUTHOR]

Treatment effects in heart failure (HF) clinical trials are typically summarized as hazard ratios (HR). However, a HR alone without a reference value of the hazard from the control arm is difficult to interpret and is valid only when hazards are proportional throughout the trial. The restricted mean survival time (RMST) describes the mean time free from an event and does not require any model assumption. Comparison of RMSTs between treatment and control arms, either by differences or ratios, is a more intuitive summary of treatment effects than HR. Compare RMST with HR in HF device clinical trials. Time-to-event data was reconstructed from published Kaplan-Meier curves from landmark HF trials. We calculated the RMST-differences and restricted mean time loss (RMTL) ratios between treatment groups as measures of treatment effect, and compared statistical testing results to HR. We analyzed 4 clinical trials with a total of 5,186 patients. Statistical significance tests were concordant between HR and RMST or RMTL for all outcomes (Table 1). However, RMST analyses provided additional clinically useful information: for instance, in COAPT, percutaneous mitral valve repair extended each patient's life 1.7 months on average compared to medical therapy alone, over 2 years follow up. In MADIT II, implantable cardioverter defibrillator (ICD) implantation extended each patient's life on average by 2.9 months compared to medical therapy, over the 4 years of the trial, and in MADIT-CRT, cardiac resynchronization therapy added on average 3.2 months to each patient's life compared to ICD alone, over 4 years of follow up. RMST achieved similar statistical testing results as HR but provides an intuitive estimate of treatment effect. RMST-based analysis may better communicate treatment effects to patients, to assist in patient-preference discussions and shared decision-making. [ABSTRACT FROM AUTHOR]

In patients with heart failure (HF), loop diuretics including torsemide and furosemide are a cornerstone of therapy for volume overload. Torsemide may be associated with enhanced natriuresis which could hemodynamically lead to worsening renal function (WRF). If renal hypoperfusion is persistent and severe, renal tubular injury (RTI) may occur but WRF does not always correlate with renal tubular injury. Urinary biomarker analysis can help identify when renal tubular injury occurs. In patients with chronic HF, use of torsemide is associated with higher biomarker levels of urinary RTI compared to furosemide. Urine samples were collected from patients with chronic HF who had been treated for at least one month with furosemide (n=15) or torsemide (n=10). Urinary concentrations of the following biomarkers were compared between groups: albumin, β-2 microglobulin (β2M), CystatinC, epidermal growth factor (EGF), neutrophil gelatinase-associated lipocalin (NGAL), osteopontin (OPN), and uromodulin. One patient in the furosemide group had outliers in several biomarkers and was excluded from the analysis. All urinary markers were present in higher concentration in the torsemide group. Using a nonparametric Wilcoxon test, statistically significant differences were found in the distribution of urinary albumin (p =0.001), β-2M (p =0.03), and NGAL (p =.04) between the two groups. Significantly higher levels of RTI biomarkers in the torsemide group suggest that there may be a greater degree of WRF with torsemide compared with furosemide. More significant differences between other urinary biomarkers may be seen with a greater sample size. This study was limited by sample size and inability to compare concentration of urine. Further study is warranted to explore the difference in these groups. [ABSTRACT FROM AUTHOR]

Clinical trial efficiency is a barrier to success in heart failure research. The Heart Failure Collaboratory (HFC) is a consortium developed to address this barrier. HFC performed a cross-sectional survey of sponsors active in the heart failure field. From August to September 2018, self-administered survey data were electronically collected from industry partners, using a 10 item survey comprising 3 domains and 10 sub-domains ranging from 'improving efficiency' to 'improving patient access.' The scale response utilized two Likert type scale of agreement. Item responses were aggregated into binary responses to create 'most efficient' or 'largest impediment' responses. Group comparisons were made via Fisher's Exact or chi-square test, where appropriate. All statistical analyses were conducted using SAS (ver. 9.3, Cary NC). 125 potential participants were emailed a link to the online survey, with 43 participants (57.3%) completing the survey for an overall response rate of 34.4%. Respondents rated the US FDA (44.2%), Health Canada (39.5%) and European Medicines Agency (EMA) (32.6%) as agencies most efficient and agencies currently available with opportunities for the most improvement in efficiency (US FDA [46.5%], EMA [20.9%], and Health Canada [4.7%]). Participants rated the top 3 items of concern as ' assuming more information will be required later by payers ' (58.1%), ' variability across global agencies ' (53.5%), and ' assuming more information will be required later by regulatory agencies ' (48.8%) (Figure). Respondents rated items of ' excessive clinical staff workload ' (55.8%), ' CRF complexity; difficulty entering data ' (51.2%) and ' deficiencies in site training ' (39.5%) as the top 3 factors influencing data quality. Respondents rated items of ' excessively onerous prior authorization ' (51.2%), ' availability of decision-making rationale ' (46.5%) and ' rationality of access barriers ' (44.2%) as the top 3 impediments to improving patient access to approved therapies. This survey of industry respondents suggests substantial barriers to clinical trial efficiency within the HF landscape. [ABSTRACT FROM AUTHOR]

With the current landscape of approved therapies for heart failure (HF), there is a need to determine the role of a standard background therapy against which novel therapies are studied. The Heart Failure Collaboratory convened a multistakeholder group of clinical investigators, clinicians, patients, government representatives including U.S. Food and Drug Administration and National Institutes of Health participants, payers, and industry in March 2021 to discuss whether standardization of background drug therapy is necessary in clinical trials in patients with HF. The current paper summarizes the discussion and provides potential conceptual approaches, with a focus on therapies indicated for HF with reduced ejection fraction. [ABSTRACT FROM AUTHOR]

Left ventricular assist devices (LVADs) mechanically unload the heart and coupled with neurohormonal therapy can promote reverse cardiac remodeling and myocardial recovery. Minimally invasive LVAD decommissioning with the device left in place has been reported to be safe over short-term follow-up. Whether device retention reduces long-term safety, or sustainability of recovery is unknown. This is a dual-center retrospective analysis of patients who had achieved responder status (left ventricular ejection fraction, LVEF ≥40% and left ventricular internal diastolic diameter, LVIDd ≤6.0 cm) and underwent elective LVAD decommissioning for myocardial recovery from May 2010 to January 2020. All patients had outflow graft closure and driveline resection with the LVAD left in place. Emergent LVAD decommissioning for an infection or device thrombosis was excluded. Patients were followed with serial echocardiography for up to 3-years. The primary clinical outcome was survival free of heart failure hospitalization, LVAD reimplantation, or transplant. During the study period 515 patients received an LVAD and 29 (5.6%) achieved myocardial recovery, 12 patients underwent total device explantation or urgent device decommissioning, 17 patients underwent elective LVAD decommissioning, and were included in the analysis. Median age of patients at LVAD implantation was 42 years (interquartile range, IQR: 25-54 years), all had a nonischemic cardiomyopathy, and 5 (29%) were female. At LVAD implantation, median LVEF was 10% (IQR: 5%-15%), and LVIDd 6.6 cm (IQR: 5.8-7.1 cm). There were 11 hydrodynamically levitated centrifugal-flow (65%), and 6 axial-flow LVADs (35%). The median duration of LVAD support before decommissioning was 28.7 months (range 13.5-36.2 months). As compared to the turndown study parameters, 1-month post-decommissioning, median LVEF decreased from 55% to 48% (p = 0.03), and LVIDd increased from 4.8 cm to 5.2 cm (p = 0.10). There was gradual remodeling until 6 months, after which there was no statistical difference on follow-up through 3-years (LVEF 42%, LVIDd 5.6 cm). Recurrent infections affected 41% of patients leading to 3 deaths and 1 complete device explant. Recurrent HF occurred in 1 patient who required a transplant. Probability of survival free of HF, LVAD, or transplant was 94% at 1-year, and 78% at 3-years. LVAD decommissioning for myocardial recovery was associated with excellent long-term survival free from recurrent heart failure and preservation of ventricular size and function up to 3-years. Reducing the risk of recurrent infections, remains an important therapeutic goal for this management strategy. [ABSTRACT FROM AUTHOR]

Ventricular assist device (VAD) patients often experience infections, which increase the risk of stroke and mortality. Using the definitions of the International Society for Heart and Lung Transplantation (ISHLT), we have characterized differences in clinical outcomes for categories of infection: VAD-specific (e.g., pump component related); VAD-related (e.g., bloodstream infection, BSI); and non-VAD infections (e.g., pneumonia). Querying of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) identified 16,597 continuous-flow VAD recipients. Categories of infection were tested in multivariate models to determine the risk of stroke and death. After implant, 7,046 patients (42%) developed an infection at a median of 69 (interquartile range 12 to 272) days. A majority were non-VAD infections (49%), followed by VAD-related (26%) and VAD-specific infections (25%). BSIs were the most common form of VAD-related infection (92%), and the majority (59%) had no associated infection, that is, idiopathic bacteremia. Internal pump component infections were rare (0.003 event per patient-year [EPPY]). Infected VAD patients had a higher prevalence of stroke compared to patients without an infection (18% vs 11%, p < 0.001). The lowest stroke rate occurred after a VAD-specific infection (0.11 EPPY) compared with VAD-related (0.17 EPPY) and non-VAD infections (0.15 EPPY, p < 0.001). Hemorrhagic strokes were more common than ischemic strokes in all infection groups and highest after a VAD-related infection (0.13 EPPY). One-year survival after an infection was 87% in VAD-specific infections, as compared with VAD-related (71%) and non-VAD infections (72%, p < 0.001). The ISHLT categorization of VAD infections unveils notable differences in associated risk of stroke and mortality. A re-assessment of transplant prioritization for eligible infected VAD patients may be useful to increase transplant-related survival benefit. [ABSTRACT FROM AUTHOR]

Background: Cardiogenic shock (CS) is a multifactorial, hemodynamically complex syndrome associated with high mortality. Despite advances in reperfusion and mechanical circulatory support, management remains highly variable and outcomes poor.Objectives: This study investigated whether a standardized team-based approach can improve outcomes in CS and whether a risk score can guide clinical decision making.Methods: A total of 204 consecutive patients with CS were identified. CS etiology, patient demographic characteristics, right heart catheterization, mechanical circulatory support use, and survival were determined. Cardiac power output (CPO) and pulmonary arterial pulsatility index (PAPi) were measured at baseline and 24 h after the CS diagnosis. Thresholds at 24 h for lactate (<3.0 mg/dl), CPO (>0.6 W), and PAPi (>1.0) were determined. Using logistic regression analysis, a validated risk stratification score was developed.Results: Compared with 30-day survival of 47% in 2016, 30-day survival in 2017 and 2018 increased to 57.9% and 76.6%, respectively (p < 0.01). Independent predictors of 30-day mortality were age ≥71 years, diabetes mellitus, dialysis, ≥36 h of vasopressor use at time of diagnosis, lactate levels ≥3.0 mg/dl, CPO <0.6 W, and PAPi <1.0 at 24 h after diagnosis and implementation of therapies. Either 1 or 2 points were assigned to each variable, and a 3-category risk score was determined: 0 to 1 (low), 2 to 4 (moderate), and ≥5 (high).Conclusions: This observational study suggests that a standardized team-based approach may improve CS outcomes. A score incorporating demographic, laboratory, and hemodynamic data may be used to quantify risk and guide clinical decision-making for all phenotypes of CS. [ABSTRACT FROM AUTHOR]