Pulmonary Hypertension in Heart Failure Patients

The development of pulmonary hypertension (PH) in patients with heart failure is associated with increased morbidity and mortality. In this article, the authors examine recent changes to the definition of PH in the setting of left heart disease (PH-LHD), and discuss its epidemiology, pathophysiology and prognosis. They also explore the complexities of diagnosing PH-LHD and the current evidence for the use of medical therapies, promising clinical trials and the role of left ventricular assist device and transplantation

Right ventricular outflow tract velocity time integral-to-pulmonary artery systolic pressure ratio: a non-invasive metric of pulmonary arterial compliance differs across the spectrum of pulmonary hypertension.

Pulmonary arterial compliance (PAC), invasively assessed by the ratio of stroke volume to pulmonary arterial (PA) pulse pressure, is a sensitive marker of right ventricular (RV)-PA coupling that differs across the spectrum of pulmonary hypertension (PH) and is predictive of outcomes. We assessed whether the echocardiographically derived ratio of RV outflow tract velocity time integral to PA systolic pressure (RVOT-VTI/PASP) (a) correlates with invasive PAC, (b) discriminates heart failure with preserved ejection-associated PH (HFpEF-PH) from pulmonary arterial hypertension (PAH), and (c) is associated with functional capacity. We performed a retrospective cohort study of patients with PAH (n = 70) and HFpEF-PH (n = 86), which was further dichotomized by diastolic pressure gradient (DPG) into isolated post-capillary PH (DPG \u3c 7 mmHg; Ipc-PH, n = 54), and combined post- and pre-capillary PH (DPG ≥ 7 mm Hg; Cpc-PH, n = 32). Of the 156 patients, 146 had measurable RVOT-VTI or PASP and were included in further analysis. RVOT-VTI/PASP correlated with invasive PAC overall (ρ = 0.61, P \u3c 0.001) and for the PAH (ρ = 0.38, P = 0.002) and HFpEF-PH (ρ = 0.63, P \u3c 0.001) groups individually. RVOT-VTI/PASP differed significantly across the PH spectrum (PAH: 0.13 [0.010-0.25] vs. Cpc-PH: 0.20 [0.12-0.25] vs. Ipc-PH: 0.35 [0.22-0.44]; P \u3c 0.001), distinguished HFpEF-PH from PAH (AUC = 0.72, 95% CI = 0.63-0.81) and Cpc-PH from Ipc-PH (AUC = 0.78, 95% CI = 0.68-0.88), and remained independently predictive of 6-min walk distance after multivariate analysis (standardized β-coefficient = 27.7, 95% CI = 9.2-46.3; P = 0.004). Echocardiographic RVOT-VTI/PASP is a novel non-invasive metric of PAC that differs across the spectrum of PH. It distinguishes the degree of pre-capillary disease within HFpEF-PH and is predictive of functional capacity

Peripheral Determinants of Oxygen Utilization in Heart Failure With Preserved Ejection Fraction

The aim of this study was to determine the arteriovenous oxygen content difference (ΔAVO2) in adult subjects with and without heart failure with preserved ejection fraction (HFpEF) during systemic and forearm exercise. Subjects with HFpEF had reduced ΔAVO2. Forearm diffusional conductance for oxygen, a lumped conductance parameter that incorporates all impediments to the movement of oxygen from red blood cells in skeletal muscle capillaries into the mitochondria within myocytes, was estimated. Forearm diffusional conductance for oxygen was not different among adults with HFpEF, those with hypertension, and healthy control subjects; therefore, diffusional conductance cannot explain the reduced forearm ΔAVO2. Instead, adiposity was strongly associated with ΔAVO2, suggesting an active role for adipose tissue in reducing exercise capacity in patients with HFpEF

Statement on imaging and pulmonary hypertension from the Pulmonary Vascular Research Institute (PVRI)

Pulmonary hypertension (PH) is highly heterogeneous and despite treatment advances it remains a life-shortening condition. There have been significant advances in imaging technologies, but despite evidence of their potential clinical utility, practice remains variable, dependent in part on imaging availability and expertise. This statement summarizes current and emerging imaging modalities and their potential role in the diagnosis and assessment of suspected PH. It also includes a review of commonly encountered clinical and radiological scenarios, and imaging and modeling-based biomarkers. An expert panel was formed including clinicians, radiologists, imaging scientists, and computational modelers. Section editors generated a series of summary statements based on a review of the literature and professional experience and, following consensus review, a diagnostic algorithm and 55 statements were agreed. The diagnostic algorithm and summary statements emphasize the key role and added value of imaging in the diagnosis and assessment of PH and highlight areas requiring further research

Recurrent takotsubo cardiomyopathy in the setting of transient neurological symptoms: a case report

<p>Abstract</p> <p>Introduction</p> <p>First described in Japan, takotsubo cardiomyopathy is increasingly becoming recognized worldwide as a cause of sudden and reversible diminished left ventricular function characterized by left apical ballooning and hyperkinesis of the basal segments, often with symptoms mimicking a myocardial infarction. Associated with physical or emotional stress, its exact pathogenesis has not been established, though evidence supports a neurohumoral etiology. Additionally, recurrence of this condition is rare. In this report, we present a rare case of recurrent takotsubo cardiomyopathy in a post-menopausal woman who presented with transient neurological complaints on both occasions.</p> <p>Case presentation</p> <p>We present a rare case of a 76-year-old Caucasian woman with no history of congestive heart failure who presented to our emergency department twice with transient neurological complaints. On the first occasion, she was found to have transient aphasia which resolved within 24 hours, yet during that period she also developed symptoms of congestive heart failure and was noted to have a new, significantly depressed ejection fraction with apical akinesis and possible apical thrombus. One month after her presentation a repeat echocardiogram revealed complete resolution of all wall motion abnormalities and a return to baseline status. Seven months later she presented with ataxia, was diagnosed with vertebrobasilar insufficiency, and again developed symptoms and echocardiography findings similar to those of her first presentation. Once again, at her one-month follow-up examination, all wall motion abnormalities had completely resolved and her ejection fraction had returned to normal.</p> <p>Conclusion</p> <p>Though the exact etiology of takotsubo cardiomyopathy is unclear, a neurohumoral mechanism has been proposed. Recurrence of this disorder is rare, though it has been reported in patients with structural brain abnormalities. This report is the first to describe recurrent takotsubo cardiomyopathy in a patient with transient neurological symptoms. In our patient, as expected in patients with this condition, complete resolution of all left ventricular abnormalities occurred within a short period of time. It is important for clinicians to be aware of this increasingly recognized syndrome, including its association with recurrence, especially in the clinical setting of neurologic dysfunction.</p

Associations between cytokines, endocrine stress response, and gastrointestinal symptoms in autism spectrum disorder

PosterAutism spectrum disorder (ASD) is characterized by impairments in social communication and abnormal repetitive behavior patterns. Recent studies have shown a strong association between ASD and gastrointestinal (GI) symptomatology. Some individuals with ASD show altered reactivity to stress, as well as altered immune markers, particularly stress responsive cytokines including TNF-alpha and IL-6. To assess potential relationships between GI symptoms and stress response, we examined whether GI symptoms are associated with increases in stress-associated endocrine markers and cytokines in ASD. We also conducted exploratory analyses the examine the relationship between IL-6, TNF-alpha, cortisol, and intelligence, as well as the effects of the presence or absence of co-occurring medical conditions on the relationship between IL-6, TNF-alpha, cortisol, and GI symptoms. Given the aforementioned findings, we expected to find positive relationships between GI symptoms and biomarkers of stress, including cortisol levels, IL-6, and TNF-alpha

Symptom Phenotypes in Pulmonary Arterial Hypertension: The PAH “Symptome”

Women with pulmonary arterial hypertension (PAH) experience multiple symptoms, including dyspnea, fatigue, and sleep disturbance, that impair their health‐related quality of life (HRQOL). However, we know little about phenotypic subgroups of patients with PAH with similar, concurrent, multiple symptoms. The objectives of this study were to define the “symptome” by symptom cluster phenotypes and compare characteristics such as biomarkers, cardiac structure and function (echocardiography), functional capacity (6‐min walk distance), and HRQOL between the groups. This cross‐sectional study included 60 women with PAH. Subjects completed an assessment battery: Pulmonary Arterial Hypertension Symptom Scale, Pittsburgh Sleep Quality Index, Multidimensional Dyspnea Profile, Patient‐Reported Outcomes Measurement Information System (PROMIS®) Physical Function, PROMIS® Sleep‐Related Impairment, and the emPHasis‐10. Subjects also underwent transthoracic echocardiography, phlebotomy, 6‐min walk distance, and actigraphy. The three symptoms of dyspnea, fatigue, and sleep disturbance were used to define the symptom clusters. Other PAH symptoms, plasma and serum biomarkers, cardiac structure and function (echocardiography), exercise capacity (6‐min walk distance), sleep (actigraphy), and HRQOL were compared across phenotypes. The mean age was 50 ± 18 years, 51% were non‐ Hispanic white, 32% were non‐Hispanic Black and 40% had idiopathic PAH. Cluster analysis identified Mild (n = 28, 47%), Moderate (n = 20, 33%), and Severe Symptom Cluster Phenotypes (n = 12, 20%). There were no differences for age, race, or PAH etiology between the phenotypes. WHO functional class (p \u3c 0.001), norepinephrine levels (p = 0.029), right atrial pressure (p = 0.001), physical function (p \u3c 0.001), sleep onset latency (p = 0.040), and HRQOL (p \u3c 0.001) all differed significantly across phenotypes. We identified three distinctive symptom cluster phenotypes (Mild, Moderate, and Severe) for women with PAH that also differed by PAH‐related symptoms, physical function, right atrial pressure, norepinephrine levels, and HRQOL. These phenotypes could suggest targeted interventions to improve symptoms and HRQOL in those most severely affected

The Anemia Stress Index-Anemia, Transfusions, and Mortality in Patients with Continuous Flow Ventricular Assist Devices

We aimed to identify a simple metric accounting for peri-procedural hemoglobin changes, independent of blood product transfusion strategies, and assess its correlation with outcomes in patients undergoing left ventricular assist device (LVAD) implantation We included consecutive patients undergoing LVAD implantation at a single center between 10/1/2008 and 6/1/2014. The anemia stress index (ASI), defined as the sum of number of packed red blood cells transfused and the hemoglobin changes after LVAD implantation, was calculated for each patient at 24 h, discharge, and 3 months after LVAD implantation. Our cohort included 166 patients (80.1% males, mean age 56.3 ± 15.6 years) followed up for a median of 12.3 months. Increases in ASI per unit were associated with a higher hazard for all-cause mortality and early RV failure. The associations between the ASI and all-cause mortality persisted after multivariable adjustment, irrespective of when it was calculated (adjusted HR of 1.11, 95% CI 1.03-1.20 per unit increase in ASI). Similarly, ASI at 24 h after implant was associated with early RV failure despite multivariable adjustment (OR 1.09, 95% CI 1.05-1.14). We present a novel metric, the ASI, that is correlated with an increased risk for all-cause mortality and early RV failure in LVAD recipients

Predicting Long Term Outcome in Patients Treated With Continuous Flow Left Ventricular Assist Device: The Penn—Columbia Risk Score

Background: Predicting which patients are unlikely to benefit from continuous flow left ventricular assist device (LVAD) treatment is crucial for the identification of appropriate patients. Previously developed scoring systems are limited to past eras of device or restricted to specific devices. Our objective was to create a risk model for patients treated with continuous flow LVAD based on the preimplant variables. Methods and Results: We performed a retrospective analysis of all patients implanted with a continuous flow LVAD between 2006 and 2014 at the University of Pennsylvania and included a total of 210 patients (male 78%; mean age, 56±15; mean follow‐up, 465±486 days). From all plausible preoperative covariates, we performed univariate Cox regression analysis for covariates affecting the odds of 1‐year survival following implantation (P<0.2). These variables were included in a multivariable model and dropped if significance rose above P=0.2. From this base model, we performed step‐wise forward and backward selection for other covariates that improved power by minimizing Akaike Information Criteria while maximizing the Harrell Concordance Index. We then used Kaplan–Meier curves, the log‐rank test, and Cox proportional hazard models to assess internal validity of the scoring system and its ability to stratify survival. A final optimized model was identified based on clinical and echocardiographic parameters preceding LVAD implantation. One‐year mortality was significantly higher in patients with higher risk scores (hazard ratio, 1.38; P=0.004). This hazard ratio represents the multiplied risk of death for every increase of 1 point in the risk score. The risk score was validated in a separate patient cohort of 260 patients at Columbia University, which confirmed the prognostic utility of this risk score (P=0.0237). Conclusion: We present a novel risk score and its validation for prediction of long‐term survival in patients with current types of continuous flow LVAD support