Sean Pinney

Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) analysis of pump thrombosis in the HeartMate II left ventricular assist device

BACKGROUND Pump thrombosis remains an uncommon but potentially catastrophic complication of durable continuous-flow left ventricular assist devices (LVAD). A perceived increase in the incidence of pump thrombosis in the HeartMate II (HMII) LVAD (Thoratec, Pleasanton, CA) by clinicians prompted this analysis of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database. METHODS Between 2006 and June 2013, 8,988 United States patients aged older than 18 years received a durable LVAD. Of these, 6,910 adult patients from 132 institutions who received a HMII LVAD were entered in the INTERMACS database and constitute the study group for this analysis. RESULTS Overall survival (with censoring at transplant or explant for recovery) with the HMII LVAD was 80% at 1 year and 69% at 2 years and was not significantly different when stratified by era of implant. Freedom from device exchange or death due to thrombosis decreased from 99% at 6 months in 2009 to 94% in 2012 (p < 0.0001). Multivariable hazard function analysis showed risk factors for pump thrombosis included later implant year (p < 0.0001), younger age (p < 0.0001), higher creatinine (p = 0.002), larger body mass index (p = 0.004), white race (p = 0.0004), left ventricular ejection fraction above 20% (p = 0.02), and higher lactate dehydrogenase level at 1 month (p < 0.0001). Survival (p < 0.0001) and freedom from infection (p = 0.008) and cerebrovascular accident (p < 0.0001) were lower after pump exchange than after primary implant. CONCLUSIONS Pump exchange or death due to pump thrombosis increased during 2011 and 2012, but the magnitude of the increase remained relatively small. Survival remains high (80% at 1 year) with the HMII LVAD. Risk factor analysis suggests that a number of patient-related factors contribute to the risk of thrombosis. Markedly elevated lactate dehydrogenase in the first month is a predictor of pump thrombosis. This analysis could not examine the potential role of technical factors during implant, such as sub-optimal pump or graft positioning, changes in patient management paradigms with pump speed settings, improved recognition and change in the threshold for pump exchange, or design or production changes with the pump, as contributors to the risk of pump thrombosis.

Right ventriculo-arterial coupling in pulmonary hypertension: a magnetic resonance study

Objective To quantify right ventriculo-arterial coupling in pulmonary hypertension by combining standard right heart catheterisation (RHC) and cardiac magnetic resonance (CMR) and to estimate it non-invasively with CMR alone. Design Cross-sectional analysis in a retrospective cohort of consecutive patients. Setting Tertiary care centre. Patients 139 adults referred for pulmonary hypertension evaluation. Interventions CMR and RHC within 2 days (n=151 test pairs). Main outcome measures Right ventriculo-arterial coupling was quantified as the ratio of pulmonary artery (PA) effective elastance (Ea, index of arterial load) to right ventricular maximal end-systolic elastance (Emax, index of contractility). Right ventricular end-systolic volume (ESV) and stroke volume (SV) were obtained from CMR and adjusted to body surface area. RHC provided mean PA pressure (mPAP) as a surrogate of right ventricular end-systolic pressure, pulmonary capillary wedge pressure (PCWP) and pulmonary vascular resistance index (PVRI). Ea was calculated as (mPAP − PCWP)/SV and Emax as mPAP/ESV. Results Ea increased linearly with advancing severity as defined by PVRI quartiles (0.19, 0.50, 0.93 and 1.63 mm Hg/ml/m2, respectively; p<0.001 for trend) whereas Emax increased initially and subsequently tended to decrease (0.52, 0.67, 0.54 and 0.56 mm Hg/ml/m2; p=0.7). Ea/Emax was maintained early but increased markedly with severe hypertension (0.35, 0.72, 1.76 and 2.85; p<0.001), indicating uncoupling. Ea/Emax approximated non-invasively with CMR as ESV/SV was 0.75, 1.17, 2.28 and 3.51, respectively (p<0.001). Conclusions Right ventriculo-arterial coupling in pulmonary hypertension can be studied with standard RHC and CMR. Arterial load increases with disease severity whereas contractility cannot progress in parallel, leading to severe uncoupling.

Cardiac allograft vasculopathy: advances in understanding its pathophysiology, prevention, and treatment.

Purpose of review To discuss the current understanding of the pathogenesis, natural history, and diagnosis of cardiac allograft vasculopathy, and to outline new preventive and treatment strategies. Recent findings The central event in the development of allograft vasculopathy is the inflammatory response to immune or nonimmune–mediated endothelial damage. This response is characterized by the release of inflammatory cytokines, upregulation of cell-surface adhesion molecules, and the subsequent binding of leukocytes. Once induced, vascular smooth muscle cells proliferate and migrate from the media to form a neointima. Circulating progenitor cells are recruited to sites of arterial injury where they may then differentiate into smooth muscle cells. Because of its diffuse nature, allograft vasculopathy is best detected by intravascular ultrasound. Noninvasive tests, such as dobutamine echocardiography, are gaining in favor. Although the only definitive treatment is retransplantation, the immunosuppressant rapamycin can limit disease progression. Its synthetic derivative, everolimus, effectively prevented intimal hyperplasia in de novo transplant recipients. Summary These advances have provided hope that allograft vasculopathy may finally be manageable.

The MOGE(S) Classification for a Phenotype–Genotype Nomenclature of Cardiomyopathy: Endorsed by the World Heart Federation

In 1956, Blankerhorn and Gall (1) proposed the term myocarditis for inflammatory heart muscle disease, and myocardiosis for other heart muscle diseases. A year thereafter, Brigden (2) defined cardiomyopathies as uncommon, non-coronary heart muscle diseases. Subsequently, Goodwin and Oakley (3) defined cardiomyopathies as myocardial diseases of unknown origin, and proposed categorization of the disorders as dilated (DCM), hypertrophic (HCM), and restrictive (or obliterative) (RCM) cardiomyopathies. In 1980, the World Health Organization (WHO) and International Society and Federation of Cardiology (ISFC) established the definition of cardiomyopathies as myocardial diseases of unknown etiology, reflecting the general lack of information about the mechanism(s) of disease (4). Although WHO-ISFC retained the 3 morphological types of cardiomyopathies proposed by Goodwin and Oakley, it also introduced the term specific heart muscle disease, where the cause of myocardial dysfunction was known. The WHO-ISFC classification subsequently expanded the definition of cardiomyopathies by adding the functional component and defined cardiomyopathy as the diseases of myocardium associated with myocardial dysfunction. Two additional classes, arrhythmogenic right ventricular cardiomyopathy (ARVC) and unclassified cardiomyopathy, were introduced during the revision, and the category of the specific heart muscle disease was excluded (5). The ISFC changed its name to the World Heart Federation (WHF) in 1998 (6), and did not indulge in further revision of the recommendations for either diagnosis or management of cardiomyopathies. A substantial increase in the knowledge of the genetic basis of cardiomyopathy has occurred, and noninvasive phenotypic characterization has become significantly more sophisticated. Therefore, the American Heart Association (AHA) (7) and the European Society of Cardiology (ESC) (8) in the last decade have proposed revisions to the classification of cardiomyopathic disorders. Whereas both systems have substantial similarities and have made important recommendations, the former has described cardiomyopathies starting from the genetic basis of the etiology followed by the phenotypic description of myocardial involvement. Conversely, the ESC has retained the description in original morphofunctional categories with further subclassification into genetic (familial) and nongenetic (nonfamilial) groups. Both classifications continue to exclude specific heart muscle disease (resulting from coronary, hypertensive, valvular, and congenital heart disease) from consideration as a cardiomyopathic disorder. There is no denying the fact that most cardiomyopathies are genetic diseases, which in the real life are brought to clinical attention (and diagnosed and managed) based on a phenotypic diagnosis. More than 60 disease genes have been identified to date (9); genes such as MYBPC3 may be associated with different phenotypes (HCM, RCM, DCM), and genes such as DYS may cause a unique phenotype (DCM only). The penetrance of the genetic mutation is variable, and phenotypic manifestations are often age dependent. Most genetic cardiomyopathies are inherited as autosomal dominant traits, with a minority of families demonstrating autosomal recessive, X-linked recessive or dominant (rare), and matrilineal inheritance. Cascade family screening and follow-up have become mandatory (10). It has become necessary for a more descriptive nosology to be developed that may encompass either all attributes of the individual patient cardiomyopathy or allow a common platform for collaborative research efforts. A number of experts, including clinical cardiologists, heart failure–transplantation physicians, geneticists, and cardiovascular imagers, have proposed a systematic nomenclature endorsed by the WHF Scientific Committee. The proposed classification is a descriptive presentation of the cardiomyopathic process, which is flexibly modifiable and expandable. This nosology is inspired from the TNM staging of tumors and is being simultaneously published by the Journal of the American College of Cardiology and the official journal of the WHF, Global Heart.

The Role of Implantable Cardioverter-Defibrillators in Patients With Continuous Flow Left Ventricular Assist Devices

Background—The prognosis for patients experiencing ventricular arrhythmias (VAs) while on continuous flow left ventricular assist device (LVAD) support has not been well elucidated. Accordingly, the role of implantable cardioverter-defibrillators (ICDs) in this patient population remains undefined. Methods and Results—Records of 106 consecutive patients undergoing implantation of the HeartMate II LVAD at a single center were reviewed. For patients surviving >30 days postimplant (98 patients), the impact of VAs and ICDs on survival was analyzed. Mean age was 56.6±11.4 years, 82.1% were male, 42.5% had an ischemic cardiomyopathy, 87.7% were bridge to transplantation, and median length of support was 217 days. Twenty-one (19.8%) patients died, 60 (56.6%) survived to transplantation, and 25 patients (23.6%) reached the end of study, had the LVAD explanted, or were lost to follow-up. Post-LVAD VAs occurred in 37 patients (34.9%) but were not associated with increased mortality (hazard ratio, 0.58 [0.18–1.90]). Sixty-two (63.3%) patients had an active ICD, and 36 (36.7%) patients had no ICD or an inactivated ICD post-LVAD. Patients with an ICD were more likely to be INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) level 3 or 4 at the time of implant (54.8% versus 33.3%; P=0.04). An appropriate shock was delivered in 27.3% of patients, but the presence of an active ICD was not associated with improved survival (hazard ratio, 1.12 [0.37–3.35]). Conclusions—VAs are common in patients with continuous flow LVADs. Although some episodes may be clinically significant, VAs are not associated with a worse prognosis, and concomitant ICDs in these patients may not reduce mortality.

Donor‐Derived Trypanosoma cruzi Infection in Solid Organ Recipients in the United States, 2001–2011

Although Trypanosoma cruzi, the parasite that causes Chagas disease, can be transmitted via organ transplantation, liver and kidney transplantation from infected donors may be feasible. We describe the outcomes of 32 transplant recipients who received organs from 14 T. cruzi seropositive donors in the United States from 2001 to 2011. Transmission was confirmed in 9 recipients from 6 donors, including 3 of 4 (75%) heart transplant recipients, 2 of 10 (20%) liver recipients and 2 of 15 (13%) kidney recipients. Recommended monitoring posttransplant consisted of regular testing by PCR, hemoculture, and serology. Thirteen recipients had no or incomplete monitoring; transmission was confirmed in five of these recipients. Four of the five recipients had symptomatic disease and all four died although death was directly related to Chagas disease in only one. Nineteen recipients had partial or complete monitoring for T. cruzi infection with weekly testing by PCR, hemoculture and serology; transmission was confirmed in 4 of 19 recipients with no cases of symptomatic disease. Our results suggest that liver and kidney transplantation from T. cruzi seropositive donors may be feasible when the recommended monitoring schedule for T. cruzi infection is followed and prompt therapy with benznidazole can be administered.

Anticardiac Myosin Immunity and Chronic Allograft Vasculopathy in Heart Transplant Recipients

Chronic allograft vasculopathy (CAV) contributes to heart transplant failure, yet its pathogenesis is incompletely understood. Although cellular and humoral alloimmunity are accepted pathogenic mediators, animal models suggest that T cells and Abs reactive to graft-expressed autoantigens, including cardiac myosin (CM), could participate. To test the relationship between CAV and anti-CM autoimmunity in humans, we performed a cross-sectional study of 72 heart transplant recipients: 40 with CAV and 32 without. Sera from 65% of patients with CAV contained anti-CM Abs, whereas <10% contained Abs to other autoantigens (p < 0.05), and only 18% contained anti-HLA Abs (p < 0.05 versus anti-CM). In contrast, 13% of sera from patients without CAV contained anti-CM Abs (p < 0.05; odds ratio [OR], associating CAV with anti-CM Ab = 13, 95% confidence interval [CI] 3.79–44.6). Multivariable analysis confirmed the association to be independent of time posttransplant and the presence of anti-HLA Abs (OR = 28, 95% CI 5.77–133.56). PBMCs from patients with CAV responded more frequently to, and to a broader array of, CM-derived peptides than those without CAV (p = 0.01). Detection of either CM–peptide-reactive T cells or anti-CM Abs was highly and independently indicative of CAV (OR = 45, 95% CI 4.04–500.69). Our data suggest detection of anti-CM immunity could be used as a biomarker for outcome in heart transplantation recipients and support the need for further studies to assess whether anti-CM immunity is a pathogenic mediator of CAV.

Chagas Disease in Latin-American Immigrants with Dilated Cardiomyopathy in New York City

Chagas disease-associated cardiomyopathy is clinically similar to other causes of cardiomyopathy and, therefore, the diagnosis can be easily overlooked. We found a 13% point prevalence of Chagas disease in a sample of New York City immigrants with dilated cardiomyopathy.

Evaluation of right ventricular function and post-operative findings using cardiac computed tomography in patients with left ventricular assist devices

BACKGROUND Right ventricular (RV) failure is a major contributor to morbidity and mortality after left ventricular assist device (LVAD) implantation. Accurate evaluation of RV function in patients with LVAD remains challenging. We hypothesized that, after LVAD implantation, electrocardiographic-gated cardiac computed tomography (CCT) allows RV evaluation with higher feasibility and reproducibility compared with echocardiography. METHODS Thirty-six patients with an implanted LVAD who had 2-dimensional echocardiography and CCT evaluation were studied. RV end-diastolic and end-systolic volumes and ejection fraction were quantified using CCT. RV fractional area change, tricuspid annular plane systolic excursion and RV end-diastolic short-to-long axis ratio were calculated by echocardiography. Intraclass correlation coefficients (ICCs) and Bland-Altman analysis were used to assess intra- and interobserver reproducibility for all measurements. RESULTS The quality of CCT studies was good in all cases except for one. Intra- and interobserver reproducibility for all CCT measurements was high (interobserver ICC for RV ejection fraction = 0.89, 95% confidence interval 0.74 to 0.95). Echocardiographic indices of RV function and geometry had lower reproducibility. The echocardiographic index that best correlated with the CCT-determined RV ejection fraction was RV fractional area change (r = 0.80, p < 0.001). In addition, CCT detected relevant post-operative findings in 50% of the patients. CONCLUSIONS CCT is highly effective and reproducible compared with echocardiography for the evaluation of RV function in patients with LVAD support and provides relevant information on post-operative findings. Our results suggest that CCT should be considered as a useful imaging modality in this clinical setting.

Failed repeated thrombolysis requiring left ventricular assist device pump exchange

A 51‐year‐old male with untreated hepatitis C infection, cirrhosis, and dilated cardiomyopathy with a HeartMate II LVAD presented with right heart failure and cardiogenic shock, INR of 7, hemolysis, and renal failure. Acute LVAD thrombosis was suspected. Alteplase was injected into the inflow cannula of the LVAD with little effect. Intravenous alteplase was given but failed to restore an adequate pump output, resulting in the need for emergency pump exchange. The patient had an uncomplicated postoperative recovery and was discharged uneventfully. Inspection of the pump identified a thrombus wedged between the spines of the impeller. Our case highlights the challenges in managing pump thrombosis which is often resistant to thrombolysis and may instead rely upon prompt surgical intervention to be resolved.