Faculty Bibliography

BACKGROUND:Infection has been associated with stroke in patients with left ventricular assist devices (LVAD); however, little data exist on the timing, type and mortality impact of infection-related stroke. METHODS:Prospectively collected data of HeartMate II (N = 332) and HeartWare (N = 70) LVAD patients from a single center were reviewed. Only strokes (ischemic or hemorrhagic) that occurred within 6 weeks following a LVAD infection were considered in analyses. The association between LVAD infections (wound, pump pocket, driveline and/or bloodstream infection [BSI]), specific pathogens and ischemic and hemorrhagic strokes was evaluated using multivariable logistic regression analysis. The impact of infection-related stroke on cumulative survival was assessed using Kaplan-Meier analysis. RESULTS:Of 402 patients, LVAD infection occurred in 158 (39%) including BSI in 107 (27%), driveline infection in 67 (17%), wound infection in 31 (8%) and pump pocket infection in 24 (6%). LVAD infection-related stroke occurred in 20/158 (13%) patients in a median of 4 days (0-36 days) from documented infection. In multivariable analysis, ischemic stroke was associated with wound infection (aOR 9.0, 95% CI 2.4-34.0, P = 0.001) and BSI (aOR 7.7, 95% CI 0.9-66.0, P = 0.064), and hemorrhagic stroke was associated with BSI in 100% of cases (P = 0.01). There was no association with driveline or pump pocket infection. The cumulative survival rate among patients with infection-related stroke was significantly lower compared to those with LVAD infection but no stroke (log-rank P < 0.001). There was a trend toward shorter stroke-free survival among patients with LVAD infection. CONCLUSIONS:LVAD infections, particularly BSI, are significantly associated with stroke, and infection-related stroke conferred significantly lower cumulative survival.

Purpose: In October 2018, a new US adult heart allocation scheme was enacted in which the etiology of cardiomyopathy can play a significant role in the prioritization of patients listed for transplantation. Given this, we embarked on a review of the diagnoses of patients who underwent therapy for advanced heart failure at our center.
Method(s): We retrospectively reviewed the etiology of cardiomyopathy of patients receiving either durable ventricular assist device (VAD) or orthotopic heart transplantation (OHT) at NYU Langone Medical Center in New York, NY between January 2011 and October 2018. We evaluated for discrepancies between the primary HF diagnosis at time of operation with the ultimate diagnosis, combining both clinical follow-up data and cardiac pathology.
Result(s): During the study period, a total of 110 patients were treated with advanced therapies, of which the majority (74.5%) were male. 40.9% were African American, 35.4% Caucasian, 4.5% Asian, and 23.6% Hispanic. 86.3% underwent VAD and 22.0% underwent OHT. The average age of those undergoing OHT and VAD were 58 and 61 respectively. The most common reported etiology of HF was dilated cardiomyopathy (57.3%), followed by ischemic (36.3%), familial DCM (1.8%), amyloidosis (1.8%), restrictive cardiomyopathy (1.8%), and sarcoidosis (0.9%). On final review of the diagnoses in these patients, 14 (12.7%) had a final diagnosis that was inconsistent with the prior reported one. 5 were clerical errors, but 9 were significant deviations from the prior diagnosis. The most common diagnoses that were misidentified prior to VAD or OHT were cardiac sarcoidosis (2), cardiac amyloidosis (2), and hypertrophic cardiomyopathy (2). Among those 9 patients, 7 patients received VAD with 5 eventually requiring OHT (median days to OHT = 248); 2 patients directly received OHT. All of those are alive except one patient who was lost to follow-up (transferred care to another center). Patients in whom the diagnosis was misidentified prior to VAD or OHT had smaller LV dimensions on transthoracic echocardiography on average than other LVAD or OHT patients with non-ischemic cardiomyopathy.
Conclusion(s): In this single-center review, we found that the majority of HF patients undergoing VAD and OHT had a correct diagnosis for their heart failure prior to treatment, although notably 8.1% had a missed diagnosis at time of intervention (VAD or OHT). Appropriately identifying the subtype of cardiomyopathy remains challenging especially in advanced HF patients but can significantly impact waiting list time in the current organ allocation scheme. A normal or minimally increased LV dimension on echocardiogram in a patient with advanced non-ischemic cardiomyopathy may warrant further workup for another diagnosis.
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BACKGROUND:Little data exists regarding reversal and resumption of antithrombotics following left ventricular assist device (LVAD)-associated intracranial hemorrhage (ICH). METHODS:Prospectively collected data of LVAD patients with ICH was reviewed. Coagulopathy reversal agents, antithrombotic regimens and thrombotic (venous thromboembolism, ischemic stroke, myocardial infarction) and hemorrhagic (recurrent ICH, gastrointestinal bleed, anemia requiring transfusion) complications were recorded. RESULTS:Of 405 patients, intracranial hemorrhage occurred in 39 (10%): 23 intracerebral hemorrhages, 10 subarachnoid hemorrhages, and 6 subdural hematomas. Of 27 patients who received antithrombotic reversal, 8 (30%) had inadequate coagulopathy reversal and 3 of these had hemorrhage expansion or died before repeat imaging. One (4%) had a thrombotic complication (deep vein thrombosis). Antithrombotic therapy was resumed in 17(100%) survivors in a median time 8 days for antiplatelet agents, and 14 days for warfarin. Recurrent intracranial hemorrhage occurred within a median of 7 days of antithrombotic resumption, while ischemic stroke occurred in a median of 428 days. Patients who resumed antiplatelets alone (N=4) had a trend toward more thrombotic events (1.37 vs. 0.14 events-per-patient-year [EPPY],P=0.08), including more fatal thrombotic events (0.34 EPPY vs. 0.08, P=0.89) compared to those resuming warfarin±antiplatelet (N=14). Non-fatal hemorrhage event rates were 0.34 EPPY in the warfarin±antiplatelet vs. 0 EPPY in the antiplatelet alone group (P=0.16). No fatal hemorrhagic events occurred. CONCLUSIONS:Reversal of anticoagulation appears safe following LVAD-associated intracranial hemorrhage, though inadequate reversal was common. Resumption of warfarin±antiplatelet was associated with fewer fatal and non-fatal thrombotic events compared to antiplatelets alone, though more non-fatal hemorrhage events occurred.

Background: Heart failure (HF) hospitalization rates have remained high in the past 10 years. Numerous studies have shown significant improvement in HF readmission rates when pharmacists or pharmacy residents conduct postdischarge telephone calls. Objective: The purpose of this retrospective review of a pilot program was to evaluate the impact of pharmacy student-driven postdischarge phone calls on 30- and 90-day hospital readmission rates in patients recently discharged with HF. Methods: A retrospective manual chart review was conducted for all patients who received a telephone call from the pharmacy students. The primary endpoint compared historical readmissions, 30 and 90 days prior to hospital discharge, with 30 and 90 days post discharge readmissions. For the secondary endpoints, historical and postdischarge 30-day and 90-day readmission rates were compared for patients with a primary diagnosis of HF and for patients with a secondary diagnosis of HF. Descriptive statistics were calculated in the form of means and standard deviations for continuous variables and frequencies and percentages for categorical variables. Results: Statistically significant decrease was observed for both the 30-day (P = .006) and 90-day (P = .007) readmission periods. Prior to the pharmacy students' phone calls, the overall group of 131 patients had historical readmission rates of 24.43% within 30 days and 38.17% within 90 days after hospital discharge. After the postdischarge phone calls, the readmission rates decreased to 11.45%, for 30 days, and 22.90%, for 90 days. Conclusion: Postdischarge phone calls, specifically made by pharmacy students, demonstrated a positive impact on reducing HF-associated hospital readmissions, adding to the growing body of evidence of different methods of pharmacy interventions and highlighting the clinical impact pharmacy students may have in transition of care services.

Objective- Psoriasis is an inflammatory skin disease which heightens the risk of cardiovascular disease. This study directly investigated vascular endothelial health and systemically altered pathways in psoriasis and matched controls. Approach and Results- Twenty patients (mean age, 40 years; 50% male) with active psoriasis and 10 age-, sex-matched controls were recruited. To investigate systemically alerted pathways, a deep sequencing omics approach was applied, including unbiased blood transcriptomic and targeted proteomic analysis. Vascular endothelial health was assessed by transcriptomic profiling of endothelial cells obtained from the brachial veins of recruited participants. Blood transcriptomic profiling identified inflammasome signaling as the highest differentially expressed canonical pathway ( Z score 1.6; P=1×10^-7) including upregulation of CASP5 and interleukin ( IL) -1β. Proteomic panels revealed IL-6 as a top differentially expressed cytokine in psoriasis with pathway analysis highlighting IL-1β( Z score 3.7; P=1.02×10^-23) as an upstream activator of the observed upregulated proteins. Direct profiling of harvested brachial vein endothelial cells demonstrated inflammatory transcript (eg, IL-1β, CXCL10, VCAM-1, IL-8, CXCL1, Lymphotoxin beta, ICAM-1, COX-2, and CCL3) upregulation between psoriasis versus controls. A linear relationship was seen between differentially expressed endothelial inflammatory transcripts and psoriasis disease severity. IL-6 levels correlated with inflammatory endothelial cell transcripts and whole blood inflammasome-associated transcripts, including CASP5 and IL-1β. Conclusions- An unbiased sequencing approach demonstrated the inflammasome as the most differentially altered pathway in psoriasis versus controls. Inflammasome signaling correlated with psoriasis disease severity, circulating IL-6, and proinflammatory endothelial transcripts. These findings help better explain the heightened risk of cardiovascular disease in psoriasis. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT03228017.

Cardiogenic shock occurs in up to 5% to 10% of acute myocardial infarctions(MI) and is associated with high short- and long-term mortality risk. Since its introduction into clinical practice >50 years ago, intra-aortic balloon counterpulsion has been used empirically to provide hemodynamic support in patients undergoing coronary revascularization in the setting of MI and cardiogenic shock. In the landmark SHOCK (Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock) trial, conducted between 1993 and 1998, intra-aortic balloon pumps (IABP) were placed in 86% of participants, irrespective of the assigned management strategy.¹ Although expert opinion supported clinical benefit of IABP use in cardiogenic shock, the first large randomized, multi-center trial of IABP, published in 2012, upended this conventional wisdom. The IABP-SHOCK II(Intra-aortic Balloon Pump in Cardiogenic Shock II) trial randomly assigned 600 participants planned for early revascularization of acute MI complicated by cardiogenic shock to either IABP placement or no IABP placement.² The primary end point was 30-day all-cause mortality. At 30 days, all-cause mortality was 40%, with no difference between patients randomized to receive an IABP versus those who were not. There were no differences between treatment groups in secondary outcomes, including bleeding, ischemic complications, stroke, time to hemodynamic stabilization, intensive care unit length of stay, and the dose and duration of catecholamine therapy. A previous intermediate-term report of IABP-SHOCK II trial outcomes demonstrated no difference between treatment groups for allcause mortality at 12 months.³ In this issue of Circulation, Thiele et al⁴ report the 6-year results of the IABPSHOCK II randomized trial. At 6 years of follow-up, all-cause mortality was high and did not differ between the IABP and control groups (66.3% versus 67.0%) in intention-to-treat, per-protocol, and as-treated analyses. No signal for benefit associated with IABP use was observed in any prespecified or post hoc subgroups. There were no differences in the frequency of recurrent MI, repeat revascularization, stroke, or cardiovascular rehospitalization between the 2 groups. Quality of life, measured by the EuroQol 5D questionnaire and New York Heart Association classification, was favorable in survivors of cardiogenic shock. Four of 5 survivors had New York Heart Association Class I or II symptoms, with no difference between patients randomly assigned to IABP and no IABP therapy.