Circulatory Assist Devices 2000: An Update

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71424/1/j.1527-5299.2000.80165.x.pd

Utility of routine evaluations for rejection in patients greater than 2 years after heart transplantation

AimsGuidelines support routine surveillance testing for rejection for at least 5 years after heart transplant (HT). In patients greater than 2 years post‐HT, we examined which clinical characteristics predict continuation of routine surveillance studies, outcomes following discontinuation of routine surveillance, and the cost‐effectiveness of different surveillance strategies.Methods and resultsWe retrospectively identified subjects older than 18 who underwent a first HT at our centre from 2007 to 2016 and who survived ≥760 days (n = 217) post‐HT. The clinical context surrounding all endomyocardial biopsies (EMBs) and gene expression profiles (GEPs) was reviewed to determine if studies were performed routinely or were triggered by a change in clinical status. Subjects were categorized as following a test‐based surveillance (n = 159) or a signs/symptoms surveillance (n = 53) strategy based on treating cardiologist intent to continue routine studies after the second post‐transplant year. A Markov model was constructed to compare two test‐based surveillance strategies to a baseline strategy of discontinuing routine studies. One thousand twenty studies were performed; 835 were routine. Significant rejection was absent in 99.0% of routine EMBs and 99.8% of routine GEPs. The treating cardiologist’s practice duration, patient age, and immunosuppressive regimen predicted surveillance strategy. There were no differences in outcomes between groups. Routine surveillance EMBs cost more and were marginally less effective than a strategy of discontinuing routine studies after 2 years; surveillance GEPs had an incremental cost‐effectiveness ratio of $1.67 million/quality‐adjusted life‐year.ConclusionsAcute asymptomatic rejection is rare after the second post‐transplant year. Obtaining surveillance studies beyond the second post‐transplant year is not cost‐effective.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156231/2/ehf212745.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156231/1/ehf212745_am.pd

Statin intensity and risk for cardiovascular events after heart transplantation

AimsStatins improve survival and reduce rejection and cardiac allograft vasculopathy after heart transplantation (HT). The impact of different statin intensities on clinical outcomes has never been assessed. We set out to determine the impact of statin exposure on cardiovascular outcomes after HT.Methods and resultsWe performed a retrospective study of 346 adult patients who underwent HT from 2006 to 2018. Statin intensity was determined longitudinally after HT based on American College of Cardiology/American Heart Association (ACC/AHA) guidelines. The primary outcome was the time to the first primary event defined as the composite of heart failure hospitalization, myocardial infarction, revascularization, and all‐cause mortality. Secondary outcomes included time to significant rejection and time to moderate–severe cardiac allograft vasculopathy. Adverse events were evaluated for subjects on high‐intensity statin therapy. A Cox proportional hazards model was used to evaluate the relationship between clinical variables, statin intensity, and outcomes. Most subjects were treated with low‐intensity statin therapy although this declined from 89.9% of the population at 1month after HT to 42.8% at 5years after HT. History of ischaemic cardiomyopathy, significant acute rejection, older donor age, and lesser statin intensity (p ≤ 0.001) were associated with reduced time to the primary outcome in a multivariable Cox model. Greater intensity of statin therapy was most beneficial early after HT. There were no statin‐related adverse events for the 14 subjects on high‐intensity statin therapy.ConclusionsGreater statin intensity was associated with a reduction in adverse cardiovascular outcomes after HT.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162686/2/ehf212784.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162686/1/ehf212784_am.pd

The effect of Crataegus oxycantha special extract WS 1442 on clinical progression in patients with mild to moderate symptoms of heart failure ☆

Aim To examine whether hawthorn ( Crataegus Special Extract WS 1442 {CSE}) inhibits progression in heart failure (HF) patients. Methods We performed a retrospective analysis of data from the HERB CHF study in which patients with mild to moderate HF were randomised to either CSE 900 mg or placebo for 6months. The primary outcome was time to progression of HF (HF death, hospitalisation, or sustained increase in diuretics) as assessed by log‐rank tests and by Cox modelling. Results Progression of HF occurred in 46.6% of the CSE and 43.3% of the placebo groups (OR 1.14, 95% CI=0.56, 2.35: p =0.86). Patients receiving CSE were 3.9 times (95% CI=1.1−13.7: p =0.035) more likely to experience HF progression at baseline. In adjusted analysis, the risk of having early HF progression in the CSE group increased to 6.4 (95% CI=1.5, 26.5: p =0.011). In patients with LVEF≤35%, those taking CSE were at significantly greater risk (3.2, 95% CI=1.3, 8.3: p =0.02) than the placebo group. Conclusions CSE does not reduce heart failure progression in patients who have HF. CSE appears to increase the early risk of HF progression.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102656/1/ejhf2008-04-008.pd

Vitamin D and Cardiovascular Disease

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90252/1/phco.29.6.691.pd

Translation of immunomodulatory therapy to treat chronic heart failure: Preclinical studies to first in human

BACKGROUND: Inflammation has been associated with progression and complications of chronic heart failure (HF) but no effective therapy has yet been identified to treat this dysregulated immunologic state. The selective cytopheretic device (SCD) provides extracorporeal autologous cell processing to lessen the burden of inflammatory activity of circulating leukocytes of the innate immunologic system. AIM: The objective of this study was to evaluate the effects of the SCD as an extracorporeal immunomodulatory device on the immune dysregulated state of HF. HF. METHODS AND RESULTS: SCD treatment in a canine model of systolic HF or HF with reduced ejection fraction (HFrEF) diminished leukocyte inflammatory activity and enhanced cardiac performance as measured by left ventricular (LV) ejection fraction and stroke volume (SV) up to 4 weeks after treatment initiation. Translation of these observations in first in human, proof of concept clinical study was evaluated in a patient with severe HFrEFHFrEF ineligible for cardiac transplantation or LV LV assist device (LVAD) due to renal insufficiency and right ventricular dysfunction. Six hour SCD treatments over 6 consecutive days resulted in selective removal of inflammatory neutrophils and monocytes and reduction in key plasma cytokines, including tumor necrosis factor-alpha (TNF-α),), interleukin (IL)-6, IL-8, and monocyte chemoattractant protein (MCP)-1. These immunologic changes were associated with significant improvements in cardiac power output, right ventricular stroke work index, cardiac index and LVSV index…. Stabilization of renal function with progressive volume removal permitted successful LVAD implantation. CONCLUSION: This translational research study demonstrates a promising immunomodulatory approach to improve cardiac performance in HFrEFHFrEF and supports the important role of inflammation in the progression of HFHF

A novel, highly discriminatory risk model predicting acute severe right ventricular failure in patients undergoing continuous‐flow left ventricular assist device implant

Various risk models with differing discriminatory power and predictive accuracy have been used to predict right ventricular failure (RVF) after left ventricular assist device (LVAD) placement. There remains an unmet need for a contemporary risk score for continuous flow (CF)‐LVADs. We sought to independently validate and compare existing risk models in a large cohort of patients and develop a simple, yet highly predictive risk score for acute, severe RVF. Data from the Mechanical Circulatory Support Research Network (MCSRN) registry, consisting of patients who underwent CF‐LVAD implantation, were randomly divided into equal‐sized derivation and validation samples. RVF scores were calculated for the entire sample, and the need for a right ventricular assist device (RVAD) was the primary endpoint. Candidate predictors from the derivation sample were subjected to backward stepwise logistic regression until the model with lowest Akaike information criterion value was identified. A risk score was developed based on the identified variables and their respective regression coefficients. Between May 2004 and September 2014, 734 patients underwent implantation of CF‐LVADs [HeartMate II LVAD, 76% (n = 560), HeartWare HVAD, 24% (n = 174)]. A RVAD was required in 4.5% (n = 33) of the patients [Derivation cohort, n = 15 (4.3%); Validation cohort, n = 18 (5.2%); P = 0.68)]. 19.5% of the patients (n = 143) were female, median age at implant was 59 years (IQR, 49.4–65.3), and median INTERMACS profile was 3 (IQR, 2–3). RVAD was required in 4.5% (n = 33) of the patients. Correlates of acute, severe RVF in the final model included heart rate, albumin, BUN, WBC, cardiac index, and TR severity. Areas under the curves (AUC) for most commonly used risk predictors ranged from 0.61 to 0.78. The AUC for the new model was 0.89 in the derivation and 0.92 in the validation cohort. Proposed risk model provides very high discriminatory power predicting acute severe right ventricular failure and can be reliably applied to patients undergoing placement of contemporary continuous flow left ventricular assist devices.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150536/1/aor13413_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150536/2/aor13413.pd

Continuous Flow Left Ventricular Assist Device Improves Functional Capacity and Quality of Life of Advanced Heart Failure Patients

ObjectivesThis study sought to assess the impact of continuous flow left ventricular assist devices (LVADs) on functional capacity and heart failure-related quality of life.BackgroundNewer continuous-flow LVAD are smaller and quieter than pulsatile-flow LVADs.MethodsData from advanced heart failure patients enrolled in the HeartMate II LVAD (Thoratec Corporation, Pleasanton, California) bridge to transplantation (BTT) (n = 281) and destination therapy (DT) (n = 374) trials were analyzed. Functional status (New York Heart Association [NYHA] functional class, 6-min walk distance, patient activity scores), and quality of life (Minnesota Living With Heart Failure [MLWHF] and Kansas City Cardiomyopathy Questionnaires [KCCQ]) were collected before and after LVAD implantation.ResultsCompared with baseline, LVAD patients demonstrated early and sustained improvements in functional status and quality of life. Most patients had NYHA functional class IV symptoms at baseline. Following implant, 82% (BTT) and 80% (DT) of patients at 6 months and 79% (DT) at 24 months improved to NYHA functional class I or II. Mean 6-min walk distance in DT patients was 204 m in patients able to ambulate at baseline, which improved to 350 and 360 m at 6 and 24 months. There were also significant and sustained improvements from baseline in both BTT and DT patients in median MLWHF scores (by 40 and 42 U in DT patients, or 52% and 55%, at 6 and 24 months, respectively), and KCCQ overall summary scores (by 39 and 41 U, or 170% and 178%).ConclusionsUse of a continuous flow LVAD in advanced heart failure patients results in clinically relevant improvements in functional capacity and heart failure-related quality of life