Jill M. Gelow

The early origins of chronic heart failure: impaired placental growth and initiation of insulin resistance in childhood

Low birth weight and low placental weight predict later coronary heart disease and hypertension. This has led to the hypothesis that these diseases are initiated by foetal programming, the process by which foetal malnutrition leads to permanent changes in the body in ways that lead to chronic disease in later life. Here we examine the association between body and placental size at birth and later chronic heart failure.

Comparison of Left and Right Atrial Volume by Echocardiography Versus Cardiac Magnetic Resonance Imaging Using the Area-Length Method

Increased atrial volumes predict adverse cardiovascular events. Accordingly, accurate measurement of atrial size has become increasingly important in clinical practice. The area-length method is commonly used to estimate the volume. Disagreements between atrial volumes using echocardiography and other imaging modalities have been found. It is unclear whether this has resulted from differences in the measurement method or discrepancies among imaging modalities. We compared the right atrial (RA) and left atrial (LA) volume estimates using the area-length method for transthoracic echocardiography and cardiovascular magnetic resonance (CMR) imaging. Patients undergoing echocardiography and CMR imaging within 1 month were identified retrospectively. For both modalities, the RA and LA long-axis dimension and area were measured using standard 2- and 4-chamber views, and the volume was calculated using the area-length method for both atria. The echocardiographic and CMR values were compared using the Bland-Altman method. A total of 85 patients and 18 controls were included in the present study. The atrial volumes estimated using the area-length method were significantly smaller when measured using echocardiography than when measured using CMR imaging (LA volume 35 ± 20 vs 49 ± 30 ml/m², p <0.001, and RA volume 32 ± 23 vs 43 ± 29 ml/m², p = 0.012). The mean difference (CMR imaging minus echocardiography) was 14 ± 14 ml/m² for the LA and 10 ± 16 ml/m² for the RA volume. Similar results were found in the healthy controls. No significant intra- or interobserver variability was found within each modality. In conclusion, echocardiography consistently underestimated the atrial volumes compared to CMR imaging using the area-length method.

Organ allocation in adults with congenital heart disease listed for heart transplant: Impact of ventricular assist devices

BACKGROUND Adults with congenital heart disease (CHD) listed for heart transplantation are rarely supported by ventricular assist devices (VADs). This may be a disadvantage to their priority for organ allocation. We sought to determine the relationship between VAD implantation and successful transplantation among patients listed for heart transplant. METHODS Adults with CHD patients (N = 1,250) were identified from the United Network for Organ Sharing (UNOS) database from 1985 to 2010 and compared to patients without congenital etiology for heart failure (N = 59,606). VAD use at listing, listing status, status upgrades and reasons for upgrade prior to transplant were trended at 5-year intervals and appropriate statistical comparisons were made between groups. RESULTS Since 1985, VAD use prior to transplant has increased significantly in patients without CHD, but not in CHD patients (17% vs 3% in 2006 to 2010, p < 0.0001). CHD patients were more likely to be listed as Status 2, compared to those without (66% vs 40%, p < 0.001 for 2006 to 2010), and less likely to be upgraded to Status 1 after listing (43% vs 55%, p = 0.03). Among those upgraded to Status 1, CHD patients were less likely to have a VAD at transplant than those without (3% vs 18%, p = 0.005). VAD use was more likely to result in death in CHD patients. CONCLUSIONS VAD use is less common in CHD patients than in patients without CHD, both at the time of listing and transplantation. Reduced VAD use appears to contribute to lower listing status and organ allocation. These differences have grown more disparate over time. Separate criteria for organ allocation for CHD patients may be justified.

Clinical Predictors of Hepatic Fibrosis in Chronic Advanced Heart Failure

Background—The clinical features associated with liver disease in patients with advanced heart failure are poorly defined. We investigated the histopathologic spectrum of liver disease in a contemporary population with heart failure to identify the clinical correlates of hepatic fibrosis. Methods and Results—We identified 61 patients with advanced heart failure undergoing evaluation for ventricular assist device or cardiac transplantation from 1995 to 2006, who had liver tissue obtained during the same time period. Electronic medical records were reviewed for clinical data. Biopsy specimens were scored for hepatic fibrosis. Forty-seven patients (79.7%) had hepatic fibrosis on liver biopsy. Of these, 47% had severe fibrosis (grade 3 or 4). Relative to those without fibrosis, patients with hepatic fibrosis were more likely to have renal dysfunction, moderate or severe tricuspid regurgitation (odds ratio, 5.0; 95% CI, 1.2 to 21.7), and obstructive or mixed liver function test abnormalities (odds ratio, 5.7; 95% CI, 1.4 to 22.3). As anticipated, patients with no or mild fibrosis (grade 1 or 2) on transjugular liver biopsy were more likely to undergo ventricular assist device or heart transplant than patients with severe fibrosis (odds ratio, 7.8; 95% CI, 1.4 to 44.0). Accordingly, patients with severe fibrosis were less likely to be alive at the time of data collection (odds ratio, 0.07; 95% CI, 0.01 to 0.42). Conclusions—Hepatic fibrosis is common in patients with advanced heart failure. Renal dysfunction, significant tricuspid regurgitation and abnormal liver function tests are associated with hepatic fibrosis, but the predictive value of other clinical features is limited. Liver biopsy should be considered in patients undergoing ventricular assist device or transplant evaluation.

Ventricular Arrhythmias After Left Ventricular Assist Device

Despite advances in medical therapy, heart failure remains one of the major causes of hospitalizations and deaths in the United States. Approximately 5.7 million patients have heart failure, and it is the direct cause of death for 57 000 individuals annually.1 Although the combination of optimal medical therapy, implantable cardioverter-defibrillators (ICDs), and cardiac resynchronization therapy has reduced mortality rates, an estimated 50% of patients with heart failure still die within 5 years of diagnosis.1 Heart transplant is often the best therapeutic option for patients with end-stage heart failure; however, there has been a stable plateau of ≈2200 transplants/y in the United States due largely to limitations in organ availability.1 For patients who are facing unfavorably long wait times for heart transplantation, left ventricular assist devices (LVAD) have become a lifesaving option as a bridge to transplant. Currently, one quarter to one third of all heart transplant recipients are bridged with mechanical circulatory support before transplantation.2 Much of this support is in the form of permanent LVADs—surgically implanted mechanical assist devices that unload the left ventricle and can function in ambulatory patients (Figure 1). The use of permanent LVADs as destination therapy has increased dramatically, with evidence that they benefit patients with end-stage heart failure, despite noncandidacy for heart transplantation. Since the seminal Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure destination therapy trial in 2001, ≈1578 destination therapy LVADs have been implanted, with implant rates increasing rapidly.3,4 Figure 1. Examples of implantable cardioverter-defibrillators (ICDs) with 2 different types of left ventricular assist devices (LVADs). Posterior-anterior chest x-ray projections of biventricular ICDs in the presence of HVAD ( A ) and Heartmate II ( B ) models of LVAD. Development of LVADs dates to 1969 when the world’s first total artificial heart was implanted by Dr …

Impact of Single-Ventricle Physiology on Death After Heart Transplantation in Adults With Congenital Heart Disease

BACKGROUND Prevalence of univentricular (1V) anatomy over time and whether 1V anatomy is associated with early death after heart transplant (HTx) among recipients with adult congenital heart disease (ACHD) is unknown. We investigated changes in case-mix over time, 1V vs biventricular (2V) status, and the effect of 1V anatomy on death after HTx among ACHD recipients. METHODS The Nationwide Inpatient Sample (NIS) was used to identify ACHD HTx recipients in the United States aged 14 years or older from 1993 to 2007, divided into era 1 (1993 to 2000) and era 2 (2001 to 2007). In-hospital death was compared among recipients with 1V and 2V anatomy. Multivariable determinants associated with an increased risk of in-hospital death were sought with logistic regression models. RESULTS From a national estimate of 509 ACHD recipients, 143 were 1V and 366 were 2V. Overall, 1V in-hospital mortality (23%) was higher than for 2V (8%; p<0.001) and remained associated with in-hospital death after adjustment for other factors (odds ratio, 3.9; 95% confidence interval, 1.29 to 11.74; p=0.02). All 1V diagnoses had higher mortality than all 2V diagnoses. Despite minor fluctuations, the proportion of 1V patients did not increase over time (era 1, 36%; era 2, 30%; p=0.46). CONCLUSIONS Overall case-mix of ACHD recipients (1V vs 2V) has not changed over time. Initial 1V anatomy increases post-HTx death among ACHD recipients, whereas 2V patients have mortality rates similar to non-CHD recipients. National and international transplant registries should include specific CHD diagnoses because this factor plays such a large role in determining early outcomes.

Mechanical Circulatory Support Pathways That Maximize Post-Heart Transplant Survival

BACKGROUND Heart transplant (HTx) recipients reach transplantation through increasing numbers of support pathways, including transition from one pathway to another. Outcomes of patients successfully bridged with various support pathways are unknown. We sought to identify mechanical circulatory support pathways that maximize survival after HTx. METHODS A supplemented United Network Organ Sharing Dataset tracked status 1 HTx outcomes from 2000 to 2010. Recipients were grouped based on support pathway before HTx, including those transitioning from one pathway to another. Multivariable factors for time-related death were sought using Cox proportional hazard regression models. RESULTS We identified 13,250 status 1 HTx recipients. Initial support pathways were inotropes (n = 7,607), left ventricular assist device (LVAD [n = 4,034]), intraaortic balloon pump (n = 729), biventricular assist device (n = 521), extracorporeal membrane oxygenation (ECMO [n = 316]), and right ventricular assist device (n = 43). Multivariable analysis demonstrated that LVAD use conferred a survival advantage (hazard ratio [HR] 0.71; p < 0.001), whereas all other support pathways, including inotropes (HR 1.1; p = 0.02), right ventricular assist device (HR 1.9; p = 0.01), and ECMO (HR 2.2; p < 0.001) increased the risk of post-HTx death. Support pathway transition (both escalation and reduction) occurred in 2,175 patients. Patients who transitioned from either ECMO or biventricular assist device support at listing to LVAD-only support at HTx had improved post-HTx survival that was comparable to patients who had LVAD-only therapy throughout their course (p = 0.74). CONCLUSIONS The LVAD supported HTx recipients have better posttransplant survival than patients after all other mechanical support pathways. Survival after HTx is optimized when ECMO or biventricular assist device support can be transitioned to LVAD-only support. Our findings should aid clinical decision making and inform organ allocation policy development intended to maximize societal benefits of HTx.

Trajectories of heart failure self-care management and changes in quality of life

Introduction: Heart failure patients vary considerably in their self-care management behaviors (i.e. recognizing and responding to symptoms). The goal of this study was to identify unique patterns of change in heart failure self-care management and quantify associations between self-care management and quality of life (HRQOL) over time. Methods: A prospective cohort study among adults with symptomatic heart failure was designed to measure changes in self-care management (Self-care of Heart Failure Index) and HRQOL (Kansas City Cardiomyopathy Questionnaire) over six months. Growth mixture modeling was used to identify unique trajectories of change in self-care management. Results: The mean age (n=146) was 57 years, 70% were male, and 41% had class II heart failure. Two trajectories of self-care management were identified (entropy = 0.88). The larger trajectory (73.3%) was characterized by a significant decline in self-care management over time and no change in HRQOL. The smaller trajectory (26.7%) was characterized by marked improvements in self-care management and HRQOL. Changes in heart failure self-care management occurred in the absence of change in routine self-care maintenance behaviors, functional classification, and physical and psychological symptoms. Patients with greater physical symptoms at enrollment (odds ratio (OR) =1.04, p=0.037), larger left ventricles (OR=1.50, p=0.044), and ischemic heart failure (OR=3.84, p=0.014) were more likely to have the declining trajectory of self-care management. Higher levels of depression at enrollment were associated with reduced odds of having a decline in self-care management over time (OR=0.85, p<0.001). Conclusions: There are unique and clinically-relevant trajectories of change in heart failure self-care management that are associated with differences in HRQOL.

Blunted Responses to Heart Failure Symptoms in Adults With Mild Cognitive Dysfunction

Introduction:Mild cognitive dysfunction is common among adults with heart failure (HF). We hypothesized that mild cognitive dysfunction would be associated with poor HF self-care behaviors, particularly patients’ ability to respond to symptoms. Methods:We analyzed data on 148 participants in an observational study of symptoms in adults with moderate-to-advanced HF. Mild cognitive dysfunction was measured with the Montreal Cognitive Assessment (MoCA; range, 0–30), using cutoff scores for the general population (26) and for adults with cardiovascular disease (24). Heart failure self-care management (evaluation and response to HF symptoms) was measured with the Self-care of HF Index, and consulting behaviors (calling a provider when symptoms occur) were measured using the European HF Self-care Behavior Scale-9. Generalized linear modeling and hierarchical linear modeling were used to quantify the relationship between MoCA cutoff scores and indices of HF self-care. Results:The mean age of the sample was 57 ± 12 years, 61.5% were men, and 58.8% had class III/IV HF; the mean left ventricular ejection fraction was 28% ± 12%. Using MoCA scores of 26 and 24, respectively, 33.1% and 14.2% of the sample had mild cognitive dysfunction. Controlling for common confounders, participants with MoCA scores lower than 26 reported self-care comparable with that of participants with MoCA scores of 26 or higher. Participants with MoCA scores lower than 24, however, reported 21.5% worse self-care management (P = 0.014) and 51% worse consulting behaviors (P < 0.001) compared with participants with MoCA scores of 24 or higher. Conclusions:A disease-specific cutoff for mild cognitive dysfunction reveals marked differences patients’ ability to recognize and respond to HF symptoms when they occur. Adults with HF and mild cognitive dysfunction are a vulnerable patient group in great need of interventions that complement HF self-care.

Apical Ballooning Resulting from Limbic Encephalitis

BACKGROUND Neurogenic stunned myocardium is an increasingly recognized cause of left ventricular apical ballooning, or takotsubo cardiomyopathy. We report the first case of neurogenic stunned myocardium as a result of limbic encephalitis. METHODS This 73-year-old woman with anterograde and retrograde amnesia was investigated using electrocardiography, magnetic resonance imaging, and left ventricular angiography. RESULTS Electrocardiography showed deep T-wave inversions in multiple leads, magnetic resonance imaging demonstrated increased signal on fluid-attenuated inversion recovery images symmetrically within the medial temporal lobes consistent with limbic encephalitis. Left ventricular angiography showed apical ballooning. CONCLUSIONS Because the insula has extensive interconnections with limbic structures, limbic encephalitis could lead to alterations in the sympathetic regulation of the insular cortex resulting in neurogenic stunned myocardium.