Jennifer L. Cook

Antibody-Mediated Rejection in Cardiac Transplantation: Emerging Knowledge in Diagnosis and Management A Scientific Statement From the American Heart Association

Antibody-mediated rejection (AMR) of the cardiac allograft is a poorly defined and challenging diagnosis for transplant recipients and their clinicians. Although even its very existence in heart transplantation was debated until relatively recently, improved immunopathologic and serological techniques to detect myocardial capillary complement deposition and circulating anti-HLA (human leukocyte antigen) antibodies have led to the detection of a spectrum of newly uncovered immunologic changes that characterize AMR. The earliest standardized clinical and pathological criteria for the diagnosis of AMR in heart transplantation became available in 2004, the result of a task force assembled by the International Society for Heart and Lung Transplantation (ISHLT). In 2006, the criteria were refined by the ISHLT Immunopathology Task Force (Table 1). These revisions provide 4 categories of diagnostic criteria: clinical, histopathologic, immunopathologic, and serological assessment.1 Despite these published criteria, currently >50% of heart transplant centers make the diagnosis of AMR based on cardiac dysfunction and the lack of cellular infiltrates on the heart biopsy (preconference survey included in the ISHLT consensus article).2 More recently, the ISHLT Consensus Conference on AMR has redefined the pathological diagnosis of AMR.3 The 2013 ISHLT “Working Formulation for the Standardization of Nomenclature in the Pathologic Diagnosis of Antibody-Mediated Rejection in Heart Transplantation” was published in December 2013. This document provided an update to the 2010 consensus conference.4 It is anticipated that this update to the definition of AMR will reduce variations in the diagnosis of AMR, providing a platform for the development of standardized therapies. The goal of the present scientific statement is to provide the heart transplant professional with an overview of the current status of the diagnosis and treatment of AMR in the cardiac allograft based on recent consensus conferences and the published literature. We include recommendations to facilitate evolving standardization and strategies …

Current Diagnostic and Treatment Strategies for Specific Dilated Cardiomyopathies: A Scientific Statement from the American Heart Association

The intent of this American Heart Association (AHA) scientific statement is to summarize our current understanding of dilated cardiomyopathies. There is special emphasis on recent developments in diagnostic approaches and therapies for specific cardiomyopathies. Recommendations in this document are based on published studies, published practice guidelines from the American College of Cardiology (ACC)/AHA1 and other organizations,2,3 and the multidisciplinary expertise of the writing group. Existing evidence in epidemiology, classification, diagnosis, and management of specific cardiomyopathies is usually derived from nonrandomized observational studies, registries, case reports, or expert opinion based on clinical experience, not large-scale randomized clinical trials or systematic reviews. Therefore, in this document, rather than using the standard ACC/AHA classification schema of recommendations and level of evidence,4 we have included key management strategies at the end of each section and categorized our recommendations according to the level of consensus. Although the format of our recommendations might resemble the ACC/AHA classification of recommendations used in the ACC/AHA practice guidelines, because of the preponderance of expert opinion or level of evidence C evidence in our document, we elected to use different terminology to provide a distinction from the practice guidelines, in which stronger levels and quality of evidence with randomized clinical trials or meta-analyses are usually present.4 The levels of evidence follow the AHA and ACC methods of classifying the level of certainty of the treatment effect.4 The term dilated cardiomyopathy (DCM) refers to a spectrum of heterogeneous myocardial disorders that are characterized by ventricular dilation and depressed myocardial performance in the absence of hypertension, valvular, congenital, or ischemic heart disease.5 In clinical practice, the pathogenesis of heart failure (HF) has often been placed into 2 categories: ischemic and nonischemic cardiomyopathy. The term nonischemic cardiomyopathy has been interchangeably used with DCM. Although this …

Women With Cardiogenic Shock Derive Greater Benefit From Early Mechanical Circulatory Support: An Update From the cVAD Registry.

OBJECTIVES The aim of this analysis was to assess survival differences between men and women supported with Impella 2.5 (Abiomed Inc., Danvers) in the setting of acute myocardial infarction (AMI) complicated by cardiogenic shock (CS). BACKGROUND Data on sex differences in outcomes of CS with mechanical circulatory support are sparse. METHODS Patients enrolled in the cVAD Registry who underwent percutaneous coronary intervention (PCI) and Impella 2.5 support for CS complicating an AMI were included. Differences between men and women were examined. RESULTS In total, 180 patients were analyzed. Women (n = 49, 27.2%) were older (71.0 ± 12.8 years vs 63.8 ± 13.0, P = 0.001), smaller (BSA 1.82 ± 0.22 vs 2.04 ± 0.24 m(2) , P < 0.001), and had a higher STS mortality risk score than men (27.9 ± 17.0 vs. 20.8 ± 16.8 P = 0.01). There was no difference in survival to discharge (P = 0.3). Patients receiving the Impella 2.5 pre-PCI had significantly lower inpatient mortality than those who received support post-PCI (P = 0.003). However, the magnitude of the survival benefit was significantly greater in women who received the Impella pre-PCI as compared to men. Overall, 68.8% of women survived with pre-PCI Impella 2.5 versus 24.2% post-PCI (P = 0.005) whereas 54.2% of men survived with pre-PCI Impella 2.5 versus 40.3% post-PCI (P = 0.1, p-interaction = 0.07). No differences in timing to intervention were found between men and women. CONCLUSIONS Early initiation of hemodynamic support prior to PCI with Impella 2.5, in the setting of AMI complicated by CS, was associated with a greater survival benefit to hospital discharge in women compared to men, despite a higher predicted risk of mortality and a greater revascularization failure rate for women. (J Interven Cardiol 2016;29:248-256).

Sex Differences in the Care of Patients With Advanced Heart Failure

The patient was a frail-appearing woman slumped in a wheelchair, surrounded by her 3 children. Her head tilted slightly in greeting, but beyond her rapid and deep respiratory effort, she was too weak to move. She had been discharged 3 days previously from an outside hospital where she was confined for 3 weeks and had arrived at the academic medical center for a posthospital visit. The recent admission followed 4 others in the previous 6 months. Now, she was living at home in hospice care. The family arrived that day hoping that, as they heard from a church friend, the heart failure (HF) specialist might be able to help. The patient was more accepting, saying, “The doctors told me that I am dying, and there is nothing that they can do. I am at peace; I don’t want to be a bother to no one.” There are 5.7 million patients with HF in the United States over half of whom are women. Each year 33 700 women will die from this disease, representing 58% of all annual HF deaths.1–3 Although women and men are equally likely to have HF, women are more likely to die from it. Despite these facts, many Americans think that men are at greater risk for heart disease and that women are more likely to die from breast cancer. Why is the risk of HF in women underappreciated? The substantial numbers of women with HF with preserved ejection fraction (HFpEF) may be a contributor. It is known that HF with reduced EF (HFrEF) accounts for only a portion of patients with symptomatic HF. In a cohort of patients from Olmsted County, MN, HFrEF accounted for only 57% of patients with HF, whereas 43% of patients had an ejection fraction of >50%. Patients with …

Recommendations for the Use of Mechanical Circulatory Support: Ambulatory and Community Patient Care: A Scientific Statement from the American Heart Association

Mechanical circulatory support (MCS) offers a surgical option for advanced heart failure when optimal medical therapy is inadequate. MCS therapy improves prognosis, functional status, and quality of life.1,2 The INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) tracks patient selection and outcomes for all implanted US Food and Drug Administration–approved MCS devices. From June 2006 until December 2014, >15 000 patients received MCS, and >2000 implantations are performed annually. One-year survival with current continuous-flow devices is reported to be 80%, and 2-year survival, 70%.3 In patients awaiting heart transplantation, MCS provides a bridge to transplantation, and for others who are ineligible for heart transplantation, MCS provides permanent support or destination therapy. Indications and absolute and relative contraindications to durable MCS are listed in Table 1. View this table: Table 1. Indications and Contraindications to Durable Mechanical Support As of July 2014, 158 centers in the United States offer long-term MCS.3 Patients often live a substantial distance from the implanting center, necessitating active involvement of local first responders (emergency medical technicians, police, and fire department personnel), emergency department staff, primary care, and referring cardiologists. Because patients with MCS are becoming increasingly mobile, basic knowledge of equipment is necessary for personnel in public areas such as schools, public transportation, and airplanes/airports. Ambulatory patients with MCS can span the entire age spectrum from pediatrics to geriatrics. The aim of this document is to provide guidance for nonexperts in MCS and to facilitate the informed assessment, stabilization, and transport of the patient with MCS back to the MCS center for definitive therapy. In addition, the principles herein provide a foundation for emergency management and a framework to address the management of known MCS-associated complications and expected comorbid medical problems. Currently in the United States, the most frequently used durable devices are continuous-flow devices with …

Antibody-Mediated Rejection in Cardiac Transplantation: Emerging Knowledge in Diagnosis and Management

Antibody-mediated rejection (AMR) of the cardiac allograft is a poorly defined and challenging diagnosis for transplant recipients and their clinicians. Although even its very existence in heart transplantation was debated until relatively recently, improved immunopathologic and serological techniques to detect myocardial capillary complement deposition and circulating anti-HLA (human leukocyte antigen) antibodies have led to the detection of a spectrum of newly uncovered immunologic changes that characterize AMR. The earliest standardized clinical and pathological criteria for the diagnosis of AMR in heart transplantation became available in 2004, the result of a task force assembled by the International Society for Heart and Lung Transplantation (ISHLT). In 2006, the criteria were refined by the ISHLT Immunopathology Task Force (Table 1). These revisions provide 4 categories of diagnostic criteria: clinical, histopathologic, immunopathologic, and serological assessment.1 Despite these published criteria, currently >50% of heart transplant centers make the diagnosis of AMR based on cardiac dysfunction and the lack of cellular infiltrates on the heart biopsy (preconference survey included in the ISHLT consensus article).2 More recently, the ISHLT Consensus Conference on AMR has redefined the pathological diagnosis of AMR.3 The 2013 ISHLT “Working Formulation for the Standardization of Nomenclature in the Pathologic Diagnosis of Antibody-Mediated Rejection in Heart Transplantation” was published in December 2013. This document provided an update to the 2010 consensus conference.4 It is anticipated that this update to the definition of AMR will reduce variations in the diagnosis of AMR, providing a platform for the development of standardized therapies. The goal of the present scientific statement is to provide the heart transplant professional with an overview of the current status of the diagnosis and treatment of AMR in the cardiac allograft based on recent consensus conferences and the published literature. We include recommendations to facilitate evolving standardization and strategies …

Developing an Anti-Xa-Based Anticoagulation Protocol for Patients with Percutaneous Ventricular Assist Devices.

Because of the complexities associated with anticoagulation in temporary percutaneous ventricular assist device (pVAD) recipients, a lack of standardization exists in their management. This retrospective analysis evaluates current anticoagulation practices at a single center with the aim of identifying an optimal anticoagulation strategy and protocol. Patients were divided into two cohorts based on pVAD implanted (CentriMag (Thoratec; Pleasanton, CA) / TandemHeart (CardiacAssist; Pittsburgh, PA) or Impella (Abiomed, Danvers, MA)), with each group individually analyzed for bleeding and thrombotic complications. Patients in the CentriMag/TandemHeart cohort were subdivided based on the anticoagulation monitoring strategy (activated partial thromboplastin time (aPTT) or antifactor Xa unfractionated heparin (anti-Xa) values). In the CentriMag/TandemHeart cohort, there were five patients with anticoagulation titrated based on anti-Xa values; one patient developed a device thrombosis and a major bleed, whereas another patient experienced major bleeding. Eight patients received an Impella pVAD. Seven total major bleeds in three patients and no thrombotic events were detected. Based on distinct differences between the devices, anti-Xa values, and outcomes, two protocols were created to guide anticoagulation adjustments. However, anticoagulation in patients who require pVAD support is complex with constantly evolving anticoagulation goals. The ideal level of anticoagulation should be individually determined using several coagulation laboratory parameters in concert with hemodynamic changes in the patient’s clinical status, the device, and the device cannulation.

Renal dysfunction and chronic mechanical circulatory support: from patient selection to long-term management and prognosis.

Purpose of review The purpose of this review is to describe the effects of mechanical circulatory support (MCS) on changes in kidney function and their relationship with mortality, with an additional focus on the evaluation and management of both preimplant and post-MCS renal dysfunction. Recent findings Renal dysfunction is highly prevalent in patients referred for MCS and is associated with significantly increased mortality and postoperative acute kidney injury. Most patients, including those with renal dysfunction, experience marked early improvement in renal function with MCS, likely secondary to correction of the cardiogenic shock, volume overload, and neurohormonal activation characteristic of advanced heart failure. Currently, there are no diagnostic tests to definitively distinguish reversible forms of renal dysfunction likely to improve with MCS from irreversible renal dysfunction. Furthermore, the characteristic improvements in renal function observed in the early months of MCS are often transient, with subsequent recurrence of renal dysfunction with longer durations of support. Venous congestion, right ventricular dysfunction, and reduced pulsatility are potential mechanisms involved in resurgence of renal dysfunction following MCS. Summary With the exponential growth of MCS, research endeavors to both improve understanding of the mechanisms behind observed changes in renal function and elucidate the device-related effects on the kidney are imperative.

A Not-So-Obscure Cause of Gastrointestinal Bleeding

A 66-year-old man was admitted to the hospital with a 2-day history of fatigue, dizziness on standing, and bright red blood from the rectum that transitioned to black, tarry stools. He reported no abdominal pain, nausea, vomiting, or weight loss. He had a history of several myocardial infarctions and subsequent ischemic cardiomyopathy (ejection fraction, approximately 20%); a HeartMate II left ventricular assist device (LVAD) had been placed 2.5 months earlier as destination therapy (i.e., permanent therapy for a patient who is not a candidate for heart transplantation). He also had chronic atrial fibrillation. Medications included warfarin (target international normalized ratio [INR], 2.0 to 3.0), low-dose aspirin, amiodarone, and metoprolol. On physical examination, the patient’s skin and conjunctiva were pale. The heart rate and blood pressure (measured by automated sphygmomanometry) were 74 beats per minute and 117/99 mm Hg, respectively. A continuous hum from the LVAD was heard in the precordial region. The abdomen was soft, with normoactive bowel sounds. Melena was noted in the patient’s bed. There were no stigmata of chronic liver disease.

Assessment of Bleeding and Thrombosis Based on Aspirin Responsiveness after Continuous-Flow Left Ventricular Assist Device Placement

Pump thrombosis (PT) is a severe complication of left ventricular assist device (LVAD) support. This study evaluated PT and bleeding after LVAD placement in patients responsive to a standard aspirin dose of 81 mg using platelet inhibition monitoring compared with initial nonresponders who were then titrated upward to achieve therapeutic response. Patients ≥ 18 years of age with initial placement of HeartMate II LVAD at our institution and at least one VerifyNow Aspirin test performed during initial hospitalization were included. The primary endpoints were bleeding and PT compared between initial aspirin responders and nonresponders. Of 85 patients, 19 (22%) were nonresponsive to initial aspirin therapy. Responders and nonresponders showed similar survival (p = 0.082), freedom from suspected/confirmed PT (p = 0.941), confirmed PT (p = 0.273), bleeding (p = 0.401), and incidence rates in PT and bleeding. Among the initial responders (<500 vs. 500–549 aspirin reaction units), there were no significant differences in survival (p = 0.177), freedom from suspected/confirmed PT (p = 0.542), confirmed PT (p = 0.159), bleeding (p = 0.879), and incidence of PT and bleeding. Platelet function testing may detect resistance to standard aspirin regimens used in LVAD patients. Dose escalation in initially nonresponsive patients to achieve responsiveness may confer a similar PT risk to patients initially responsive to standard aspirin dosing without increased bleeding risk.