Symptom burden in heart failure: assessment, impact on outcomes, and management.

Evidence-based management has improved long-term survival in patients with heart failure (HF). However, an unintended consequence of increased longevity is that patients with HF are exposed to a greater symptom burden over time. In addition to classic symptoms such as dyspnea and edema, patients with HF frequently suffer additional symptoms such as pain, depression, gastrointestinal distress, and fatigue. In addition to obvious effects on quality of life, untreated symptoms increase clinical events including emergency department visits, hospitalizations, and long-term mortality in a dose-dependent fashion. Symptom management in patients with HF consists of two key components: comprehensive symptom assessment and sufficient knowledge of available approaches to alleviate the symptoms. Successful treatment addresses not just the physical but also the emotional, social, and spiritual aspects of suffering. Despite a lack of formal experience during cardiovascular training, symptom management in HF can be learned and implemented effectively by cardiology providers. Co-management with palliative medicine specialists can add significant value across the spectrum and throughout the course of HF.

Acute Decompensated Heart Failure Due to Combined Ischemic Cardiomyopathy and Cardiac Amyloidosis.

There are no established guidelines for the management of concurrent ischemic cardiomyopathy and cardiac amyloidosis due to the rarity of this phenomenon. We present the case of an African American woman in her 70s who was found to be in acute decompensated heart failure after she presented with progressive dyspnea. Initial workup revealed severe left ventricular systolic dysfunction with an ejection fraction of 20% and severe multivessel coronary artery disease, including severe left main disease. Multimodality imaging with cardiac MRI and technetium-99m pyrophosphate scintigraphy (PYP) during this hospital course revealed concurrent cardiac amyloidosis. Her systolic dysfunction was attributed to a combination of cardiac amyloidosis and ischemic cardiomyopathy. A multidisciplinary team comprised of interventional cardiology, cardiac surgery, and advanced heart failure amyloid specialists worked collaboratively to formulate an optimal treatment plan based on their collective clinical experiences and the limited literature, which ultimately resulted in a positive clinical outcome. Further investigation is needed to define treatment strategies specific to this patient population.

The AID antibody diversification enzyme is regulated by protein kinase A phosphorylation.

Antibodies, which are produced by B-lineage cells, consist of immunoglobulin heavy (IgH) and light (IgL) chains that have amino-terminal variable regions and carboxy-terminal constant regions. In response to antigens, B cells undergo two types of genomic alterations to increase antibody diversity. Affinity for antigen can be increased by introduction of point mutations into IgH and IgL variable regions by somatic hypermutation. In addition, antibody effector functions can be altered by changing the expressed IgH constant region exons through IgH class switch recombination (CSR). Somatic hypermutation and CSR both require the B-cell-specific activation-induced cytidine deaminase protein (AID), which initiates these reactions through its single-stranded (ss)DNA-specific cytidine deaminase activity. In biochemical assays, replication protein A (RPA), a ssDNA-binding protein, associates with phosphorylated AID from activated B cells and enhances AID activity on transcribed double-stranded (ds)DNA containing somatic hypermutation or CSR target sequences. This AID-RPA association, which requires phosphorylation, may provide a mechanism for allowing AID to access dsDNA targets in activated B cells. Here we show that AID from B cells is phosphorylated on a consensus protein kinase A (PKA) site and that PKA is the physiological AID kinase. Thus, AID from non-lymphoid cells can be functionally phosphorylated by recombinant PKA to allow interaction with RPA and promote deamination of transcribed dsDNA substrates. Moreover, mutation of the major PKA phosphorylation site of AID preserves ssDNA deamination activity, but markedly reduces RPA-dependent dsDNA deamination activity and severely impairs the ability of AID to effect CSR in vivo. We conclude that PKA has a critical role in post-translational regulation of AID activity in B cells.

Taking the time to get it bright: Use of ultrasound enhancing agent redirects clinical course of an unstable patient.

The use of ultrasound enhancing agents (UEA) during echocardiography helps to optimize visualization in technically difficult studies, with improved left ventricular opacification and endocardial border definition. The use of these agents may often unveil critical data that drastically alter clinical decision making. Despite the potential clinical benefits of UEA and known safety data, clinicians are still sometimes reluctant to take the time to use UEAs in unstable patients. Herein, we demonstrate a challenging case of a patient with late presentation myocardial infarction, complicated with cardiogenic shock and pseudoaneurysm formation that was not observed in non-contrast images, emblematically demonstrating the value of UEA in selected patients. .

Myocardial bridging in the era of a drug epidemic: a case report addressing the need to revisit donor organ assessment.

BACKGROUND: Myocardial bridging (MB), though typically a benign finding, may occasionally lead to syncope, myocardial infarction, arrhythmia, or sudden death. Surgical denervation of transplanted hearts complicates the management of such incidentally detected post-transplant coronary anomalies due to the lack of classic ischaemic symptoms. CASE SUMMARY: A middle-aged female underwent an uncomplicated cardiac transplantation from a healthy male donor in his early 20s who had suffered a cardiac arrest while using cocaine. Given the young donor age, a pre-transplant coronary angiogram (CAG) was deferred. However, 6-week post-transplant, routine CAG, and intravascular ultrasound revealed an extensive MB spanning a significant portion of the left anterior descending coronary artery with substantial myocardium at risk. A stress test with myocardial perfusion imaging performed to evaluate the functional significance of the bridge did not reveal any perfusion abnormalities in the myocardium at risk. DISCUSSION: In current practice, younger donors often do not undergo pre-transplantation CAG routinely performed in older donors given the lower prevalence of significant coronary disease. However, post-operatively this young donor was found to have passed on a potentially life-threatening MB to a denervated recipient, who cannot manifest typical anginal symptoms during ischaemia, thereby challenging providers to choose among strategies of watchful waiting, risk stratification, or pre-emptive intervention. In retrospect, the donor's mode of death may have signalled an underlying structural abnormality that warranted further pre-transplant characterization. In order to ensure optimal quality of transplanted hearts, young donors may warrant pre-transplant CAG despite their age, particularly those with a history of drug use or suspicious mode of death.

Sex-Based Differences in Left Ventricular Assist Device Utilization: Insights From the Nationwide Inpatient Sample 2004 to 2016.

BACKGROUND: Women comprise approximately one-third of the advanced heart failure population but may receive fewer advanced heart failure therapies including left ventricular assist devices (LVADs). During the early pulsatile-flow device era, women had higher post-LVAD mortality and increased complications. However, knowledge about these differences in the continuous-flow device era is limited. Therefore, we sought to explore temporal trends in LVAD utilization and post-LVAD mortality by sex. METHODS AND RESULTS: Patients with LVAD implantation from 2004 to 2016 were identified using the Nationwide Inpatient Sample. Trends in LVAD utilization and post-LVAD inpatient mortality were compared by sex and device era. Although LVADs are being increasingly utilized for patients with advanced systolic heart failure, women continue to represent a smaller proportion of LVAD recipients-25.8% in 2004 to 21.9% in 2016 (P for trend, 0.91). Women had increased inpatient mortality after LVAD implantation compared with men in the pulsatile-flow era (46.9% versus 31.1%, P<0.0001) but not in the continuous-flow era (13.3% versus 12.1%, P=0.27; P for interaction=0.0002). Inpatient mortality decreased for both sexes over time after LVAD, with a sharp fall in 2008 to 2009. Female sex was independently associated with increased post-LVAD inpatient mortality beyond adjustment for demographics and risk factors during the pulsatile-flow era (odds ratio, 2.13; 95% CI, 1.45-3.10; P<0.0001) but not during the continuous-flow era (1.18; 0.93-1.48; P=0.16). CONCLUSIONS: Although utilization of LVAD therapy increased over time for both sexes, LVAD implantation remains stably lower in women, which may suggest a potential underutilization of this potentially life-saving therapy. Prospective studies are needed to confirm these findings.

Submaximal oxygen uptake kinetics, functional mobility, and physical activity in older adults with heart failure and reduced ejection fraction.

BACKGROUND: Submaximal oxygen uptake measures are more feasible and may better predict clinical cardiac outcomes than maximal tests in older adults with heart failure (HF). We examined relationships between maximal oxygen uptake, submaximal oxygen kinetics, functional mobility, and physical activity in older adults with HF and reduced ejection fraction. METHODS: Older adults with HF and reduced ejection fraction (n = 25, age 75 ± 7 years) were compared to 25 healthy age- and gender-matched controls. Assessments included a maximal treadmill test for peak oxygen uptake (VO2peak), oxygen uptake kinetics at onset of and on recovery from a submaximal treadmill test, functional mobility testing [Get Up and Go (GUG), Comfortable Gait Speed (CGS), Unipedal Stance (US)], and self-reported physical activity (PA). RESULTS: Compared to controls, HF had worse performance on GUG, CGS, and US, greater delays in submaximal oxygen uptake kinetics, and lower PA. In controls, VO2peak was more strongly associated with functional mobility and PA than submaximal oxygen uptake kinetics. In HF patients, submaximal oxygen uptake kinetics were similarly associated with GUG and CGS as VO2peak, but weakly associated with PA. CONCLUSIONS: Based on their mobility performance, older HF patients with reduced ejection fraction are at risk for adverse functional outcomes. In this population, submaximal oxygen uptake measures may be equivalent to VO2 peak in predicting functional mobility, and in addition to being more feasible, may provide better insight into how aerobic function relates to mobility in older adults with HF.

Sports and Exercise in Athletes with Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease and one of the most common causes of sudden cardiac death (SCD). Current guidelines restrict the participation of patients with HCM in competitive sports, limiting the health benefits of exercise. However, many individuals with HCM have safely participated in sports, with a low incidence of SCD. Improved stratification of patients and desired activity may allow most individuals with HCM to engage in physical activity safely. Therefore, physicians should create an individualized approach in guiding each patient with HCM eager to enjoy the benefits of physical activity in a safe manner.

Pain and physical and psychological symptoms in ambulatory HIV patients in the current treatment era.

CONTEXT: HIV infection has become a manageable chronic disease. There are few studies of pain and symptoms in the current treatment era. OBJECTIVES: Our primary objective was to determine the prevalence of and risk factors for pain and physical and psychological symptoms in a population of ambulatory HIV patients. METHODS: We performed a cross-sectional study using the Brief Pain Inventory and the Memorial Symptom Assessment Scale-Short Form (MSAS). RESULTS: We evaluated 156 individuals with a median age of 47.5 years (range 21-71), median time since HIV diagnosis of 11 years (range <1 to 25), and median CD4+ cell count of 502 cells/mm(3) (interquartile range [IQR] 308-683). Most (125, 80.6%) of the patients had an undetectable viral load. Seventy-six (48.7%) patients reported pain, of whom 39 (51.3%) had moderate to severe pain, and 43 (57.3%) had pain that caused moderate to severe interference with their lives. The median number of symptoms was eight (IQR 5-14.5) of 32 queried. In multivariable analyses, patients with psychiatric illness were 39.8% more likely to have pain (P<0.001). Psychiatric illness was associated with 0.7 and 1.2 point higher MSAS subscale scores, and IV drug use was associated with 0.4 and 0.5 higher subscale scores (out of four). CONCLUSION: Pain and other physical and psychological symptoms were common among ambulatory HIV patients. Pain and symptoms were strongly associated with psychiatric illness and IV drug use. Future investigation should evaluate interventions that include psychiatric and substance abuse components for HIV patients with pain.