Non-Concordance between Patient and Clinician Estimates of Prognosis in Advanced Heart Failure.

IMPORTANCE: Despite efforts to enhance serious illness communication, patients with advanced heart failure (HF) lack prognostic understanding. OBJECTIVES: To determine rate of concordance between HF patients' estimation of their prognosis and their physician's estimate of the patient's prognosis, and to compare patient characteristics associated with concordance. DESIGN: Cross-sectional analysis of a cluster randomized controlled trial with 24-month follow-up and analysis completed on 09/01/2020. Patients were enrolled in inpatient and outpatient settings between September 2011 to February 2016 and data collection continued until the last quarter of 2017. SETTING: Six teaching hospitals in the U.S. PARTICIPANTS: Patients with advanced HF and implantable cardioverter defibrillators (ICDs) at high risk of death. Of 537 patients in the parent study, 407 had complete data for this analysis. INTERVENTION: A multi-component communication intervention on conversations between HF clinicians and their patients regarding ICD deactivation and advance care planning. MAIN OUTCOME(S) AND MEASURE(S): Patient self-report of prognosis and physician response to the "surprise question" of 12-month prognosis. Patient-physician prognostic concordance (PPPC) measured in percentage agreement and kappa. Bivariate analyses of characteristics of patients with and without PPPC. RESULTS: Among 407 patients (mean age 62.1 years, 29.5% female, 42.4% non-white), 300 (73.7%) dyads had non-PPPC; of which 252 (84.0%) reported a prognosis >1 year when their physician estimated <1 year. Only 107 (26.3%) had PPPC with prognosis of ≤ 1 year (n=20 patients) or > 1 year (n=87 patients); (Κ = -0.20, p = 1.0). Of those with physician estimated prognosis of < 1 year, non-PPPC was more likely among patients with lower symptom burden- number and severity (both p ≤.001), without completed advance directive (p=.001). Among those with physician prognosis estimate > 1 year, no patient characteristic was associated with PPPC or non-PPPC. CONCLUSIONS AND RELEVANCE: Non-PPPC between HF patients and their physicians is high. HF patients are more optimistic than clinicians in estimating life expectancy. These data demonstrate there are opportunities to improve the quality of prognosis disclosure between patients with advanced HF and their physicians. Interventions to improve PPPC might include serious illness communication training.

Prognostic Awareness and Goals of Care Discussions Among Patients With Advanced Heart Failure.

BACKGROUND: Prognostic awareness (PA)-the understanding of limited life expectancy-is critical for effective goals of care discussions (GOCD) in which patients discuss their goals and values in the context of their illness. Yet little is known about PA and GOCD in patients with advanced heart failure (HF). This study aims to determine the prevalence of PA among patients with advanced HF and patient characteristics associated with PA and GOCD. METHODS: We assessed the prevalence of self-reported PA and GOCD using data from a multisite communication intervention trial among patients with advanced HF with an implantable cardiac defibrillator at high risk of death. RESULTS: Of 377 patients (mean age 62 years, 30% female, 42% nonwhite), 78% had PA. Increasing age was a negative predictor of PA (odds ratio, 0.95 [95% CI, 0.92-0.97]; P<0.01). No other patient characteristics were associated with PA. Of those with PA, 26% had a GOCD. Higher comorbidities and prior advance directives were associated with GOCD but were of only borderline statistical significance in a fully adjusted model. Symptom severity (odds ratio, 1.77 [95% CI, 1.19-2.64]; P=0.005) remained a robust and statistically significant positive predictor of having a GOCD in the fully adjusted model. CONCLUSIONS: In a sample of patients with advanced HF, the frequency of PA was high, but fewer patients with PA discussed their end-of-life care preferences with their physician. Improved efforts are needed to ensure all patients with advanced HF have an opportunity to have GOCD with their doctors. Clinicians may need to target older patients with HF and continue to focus on those with signs of worsening illness (higher symptoms). Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01459744.

Evaluation of a Novel Educational Intervention to Improve Conversations About Implantable Cardioverter-Defibrillators Management in Patients with Advanced Heart Failure.

Background: Implantable cardioverter-defibrillators (ICDs) reduce the incidence of sudden cardiac death for high-risk patients with heart failure (HF), but shocks from these devices can also cause pain and anxiety at the end of life. Although professional society recommendations encourage proactive discussions about ICD deactivation, clinicians lack training in conducting these conversations, and they occur infrequently. Methods: As part of a six-center randomized controlled trial, we evaluated the educational component of a multicomponent intervention shown to increase conversations about ICD deactivation by clinicians who care for a subset of patients with advanced HF. This consisted of a 90-minute training workshop designed to improve the quality and frequency of conversations about ICD management. To characterize its utility as an isolated intervention, we compared HF clinicians' pre- and postworkshop scores (on a 5-point Likert scale) assessing self-reported confidence and skills in specific practices of advance care planning, ICD deactivation discussions, and empathic communication. Results: Forty intervention-group HF clinicians completed both pre- and postworkshop surveys. Preworkshop scores showed high baseline levels of confidence (4.36, standard deviation [SD] = 0.70) and skill (4.08, SD = 0.72), whereas comparisons of pre- and postworkshop scores showed nonsignificant decreases in confidence (-1.16, p = 0.252) and skill (-0.20, p = 0.843) after the training session. Conclusions: Our findings showed no significant changes in self-assessment ratings immediately after the educational intervention. However, our data did demonstrate that HF clinicians had high baseline self-perceptions of their skills in advance care planning conversations and appear to be well-primed for further professional development to improve communication in the setting of advanced HF.

Safety of Sports for Young Patients With Implantable Cardioverter-Defibrillators: Long-Term Results of the Multinational ICD Sports Registry.

BACKGROUND: Despite safety concerns, many young patients with implantable cardioverter-defibrillators (ICDs) participate in sports. We undertook a prospective, multinational registry to determine the incidence of serious adverse events because of sports participation. The primary end points were death or resuscitated arrest during sports or injury during sports because of arrhythmia or shock. Secondary end points included system malfunction and incidence of ventricular arrhythmias requiring multiple shocks for termination. METHODS: Athletes with ICDs aged ≤21 years were included in this post hoc subanalysis of the ICD Sports Registry. Data on sports and clinical outcomes were obtained by phone interview and medical records review. ICD shocks and clinical details of lead malfunction were classified by 2 electrophysiologists. RESULTS: A total of 129 young athletes participating in competitive (n=117) or dangerous (n=12) sports were enrolled. The mean age was 16 years (range, 10-21; 40% female; 92% white). The most common diagnoses were long QT syndrome (n=49), hypertrophic cardiomyopathy (n=30), and congenital heart disease (n=16). The most common sports were basketball and soccer, including 79 varsity/junior varsity high school and college athletes. During a median follow-up of 42 months, 35 athletes (27%) received 38 shocks. There were no occurrences of death, arrest, or injury related to arrhythmia, during sports. There was 1 ventricular tachycardia/ventricular fibrillation storm during competition. Freedom from lead malfunction was 92.3% at 5 years and 79.6% at 10 years. CONCLUSIONS: Although shocks related to competition/practice are not uncommon, there were no serious adverse sequelae. Lead malfunction rates were similar to previously reported in unselected pediatric ICD populations. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00637754.

Association of Depressive Symptoms and Heart Rate Variability in Vietnam War-Era Twins: A Longitudinal Twin Difference Study.

Importance: Depressive symptoms are associated with lower heart rate variability (HRV), an index of autonomic dysregulation, but the direction of the association remains unclear. Objective: To investigate the temporal association between depression and HRV. Design, Settings, and Participants: A longitudinal, cross-lagged twin difference study, with baseline assessments from March 2002 to March 2006 (visit 1) and a 7-year follow-up (visit 2) at an academic research center with participants recruited from a national twin registry. Twins (n = 166) from the Vietnam Era Twin Registry, who served in the US military during the Vietnam War, and were discordant for depression at baseline were recruited. Main Outcomes and Measures: At both visits, depressive symptoms were measured using the Beck Depression Inventory-II (BDI-II), and HRV was measured through 24-hour electrocardiogram monitoring. To assess the direction of the association, within-pair differences in multivariable mixed-effects regression models were examined, and standardized ß coefficients for both pathways were calculated. The associations were evaluated separately in monozygotic and dizygotic twins. Results: In the final analytic sample (N = 146), all participants were men, 138 (95%) were white, and the mean (SD) age was 54 (3) years at baseline. Results showed consistent associations between visit 1 HRV and visit 2 BDI score across all HRV domains and models (ß coefficients ranging from -0.14 to -0.29), which were not explained by antidepressants or other participant characteristics. The magnitude of the association was similar in the opposite pathway linking visit 1 BDI score to visit 2 HRV, with ß coefficients ranging from 0.05 to -0.30, but it was largely explained by antidepressant use. In stratified analysis by zygosity, significant associations were observed in monozygotic and dizygotic twins for the path linking visit 1 HRV to visit 2 BDI score, although the associations were slightly stronger in dizygotic twins. Conclusions and Relevance: The association between depression and autonomic dysregulation, indexed by HRV, is bidirectional, with stronger evidence suggesting that autonomic function affects depression risk rather than vice versa. The opposite causal pathway from depression to lower HRV is mostly driven by antidepressant use. These findings highlight an important role of autonomic nervous system in the risk of depression and contribute new understanding of the mechanisms underlying the comorbidity of depression and cardiovascular disease.

Simplified Quantification and Acquisition Protocol for 123I-MIBG Dynamic SPECT.

Previous studies have demonstrated the feasibility of absolute quantification of dynamic 123I-metaiodobenzylguanidine (123I-MIBG) SPECT imaging in humans. This work reports a simplified quantification method for dynamic 123I-MIBG SPECT using practical protocols with shortened acquisition time and voxel-by-voxel parametric imaging. Methods: Twelve healthy human volunteers underwent five 15-min dynamic SPECT scans at 0, 15, 90, 120, and 180 min after 123I-MIBG injection. List-mode SPECT data were binned into 29 frames and reconstructed with corrections for attenuation, scatter, and decay. Population-based blood-to-plasma correction and metabolite correction were applied to the image-derived input function. Likelihood estimation in graphical analysis (LEGA) was used as a simplified model to obtain volume of distribution (VT) values, which were compared with those obtained with the reversible 2-tissue (2T) compartment model. Three simplified protocols were evaluated with 2T and LEGA using a 30-min scan started simultaneously with tracer injection plus a 15-min scan at 90, 120, or 180 min after injection. Voxel-by-voxel LEGA fitting was applied to the aligned dynamic images using both the full protocol (five 15-min scans) and the simplified protocols. Results: Correlation analysis (y = 0.955x + 0.547, R2 = 0.997) and Bland-Altman plot (mean difference, -0.8 mL/cm3; 95% limits of agreement, [-2.5, 1.0] mL/cm3; normal VT range, 29.0 ± 12.4 mL/cm3) showed that LEGA can be used as a simplified model of 2T for 123I-MIBG. High-quality VT parametric images could be obtained with LEGA. Region-of-interest (ROI) modeling and parametric imaging results were in excellent agreement as determined by correlation analysis (y = 0.999x - 1.026, R2 = 0.982) and Bland-Altman plot (mean difference, -1.0 mL/cm3; 95% limits of agreement, [-4.2, 2.1] mL/cm3). VT correlated reasonably well between all simplified protocols and the full protocol with LEGA but not with 2T. The VT results were more reliable when there was a longer interval between the 2 acquisitions in the simplified protocols. Conclusion: For ROI-based kinetic modeling and parametric imaging, reliable quantification of dynamic 123I-MIBG SPECT can be achieved with LEGA using a simplified protocol of a 30-min scan starting with tracer injection plus a 15-min scan no earlier than 180 min after injection.

A blind deconvolution method incorporated with anatomical-based filtering for partial volume correction: Validations with 123 I-mIBG cardiac SPECT/CT.

PURPOSE: Segmentation of contrast-enhanced CT and measurement of SPECT point spread function (PSF) are usually required for conventional partial volume correction (PVC). This study was to develop a segmentation-free method with blind deconvolution (BD) and anatomical-based filtering for SPECT PVC. METHODS: The proposed method was implemented using an iterative BD algorithm to estimate the restored image and the PSF simultaneously. An anatomical-based filtering was implemented at each iteration to reduce Gibbs artifact and suppress noise amplification in the deconvolution process. The proposed method was validated with 123 I-metaiodobenzylguanidine (123 I-mIBG) SPECT/CT imaging of NCAT phantoms with and without myocardial perfusion defect and a physical cardiac phantom. Fifteen heart-to-mediastinum ratios (HMRs) were configured in the NCAT and physical phantoms. Correlations between SPECT-quantified and true HMRs were calculated from images without PVC as well as from BD restored images. The proposed method was also performed on a human 123 I-mIBG study. RESULTS: Relative bias and standard deviation images of NCAT phantoms showed that the proposed method reduced both bias and noise. Mean relative bias in the simulated normal myocardium was markedly improved (-16.8% ± 0.4% versus -0.8% ± 0.6% for low noise level; -16.7% ± 0.7% versus -2.3% ± 0.9% for high noise level). Mean relative bias in the simulated myocardial defect was also noticeably improved (-12.7% ± 1.2% versus 1.2% ± 1.6% for low noise level; -13.5% ± 2.4% versus -0.9% ± 2.8% for high noise level). The signal to noise ratio (SNR) of the defect was improved from 2.95 ± 0.09 to 4.07 ± 0.16 for low noise level (38% increase of mean), and from 2.56 ± 0.15 to 3.62 ± 0.22 for high noise level (41% increase of mean). For both NCAT and physical phantoms, HMRs calculated from images without PVC were underestimated (correlations between SPECT-quantified and true HMRs: y = 0.81x + 0.1 for NCAT phantom; y = 0.82x + 0.14 for physical phantom). HMRs from BD restored images were markedly improved (correlations between SPECT-quantified and true HMRs: y = x + 0.05 for NCAT phantom; y = 0.97x - 0.12 for physical phantom). After applying the proposed PVC method, the estimation error between the SPECT-quantified and true HMRs was significantly reduced from -0.75 ± 0.57 to 0.04 ± 0.17 for NCAT phantom (P = 8e-05), and from -0.68 ± 0.67 to -0.26 ± 0.42 for physical phantom (P = 0.005). The human study demonstrated that the HMR increased by 8% with PVC. CONCLUSIONS: The proposed segmentation-free PVC method has the potential of improving SPECT quantification accuracy and reducing noise without the need for premeasuring the image PSF.

Sports Cardiology: Core Curriculum for Providing Cardiovascular Care to Competitive Athletes and Highly Active People.

The last few decades have seen substantial growth in the populations of competitive athletes and highly active people (CAHAP). Although vigorous physical exercise is an effective way to reduce the risk of cardiovascular (CV) disease, CAHAP remain susceptible to inherited and acquired CV disease, and may be most at risk for adverse CV outcomes during intense physical activity. Traditionally, multidisciplinary teams comprising athletic trainers, physical therapists, primary care sports medicine physicians, and orthopedic surgeons have provided clinical care for CAHAP. However, there is increasing recognition that a care team including qualified CV specialists optimizes care delivery for CAHAP. In recognition of the increasing demand for CV specialists competent in the care of CAHAP, the American College of Cardiology has recently established a Sports and Exercise Council. An important primary objective of this council is to define the essential skills necessary to practice effective sports cardiology.

Quantitative Analysis of Dynamic 123I-mIBG SPECT Imaging Data in Healthy Humans with a Population-Based Metabolite Correction Method.

UNLABELLED: Conventional 2-dimensional planar imaging of (123)I-metaiodobenzylguanidine ((123)I-mIBG) is not fully quantitative. To develop a more accurate quantitative imaging approach, we investigated dynamic SPECT imaging with kinetic modeling in healthy humans to obtain the myocardial volume of distribution (VT) for (123)I-mIBG. METHODS: Twelve healthy humans underwent 5 serial 15-min SPECT scans at 0, 15, 90, 120, and 180 min after bolus injection of (123)I-mIBG on a hybrid cadmium zinc telluride SPECT/CT system. Serial venous blood samples were obtained for radioactivity measurement and radiometabolite analysis. List-mode data of all the scans were binned into frames and reconstructed with attenuation and scatter corrections. Myocardial and blood-pool volumes of interest were drawn on the reconstructed images to derive the myocardial time-activity curve and input function. A population-based blood-to-plasma ratio (BPR) curve was generated. Both the population-based metabolite correction (PBMC) and the individual metabolite correction (IMC) curves were generated for comparison. VT values were obtained from different compartment models, using different input functions with and without metabolite and BPR corrections. RESULTS: The BPR curve reached the peak value of 2.1 at 13 min after injection. Parent fraction was approximately 58% ± 13% at 15 min and stabilized at approximately 40% ± 5% by 180 min after injection. Two radiometabolite species were observed. When the reversible 2-tissue-compartment fit was used, the mean VT value was 29.0 ± 12.4 mL/cm(3) with BPR correction and PBMC, a 188% ± 32% increase compared with that without corrections. There was significant difference in VT with BPR correction (P = 2.3e-04) as well as with PBMC (P = 1.6e-05). The mean difference in VT between PBMC and IMC was -3% ± 8%, which was insignificant (P = 0.39). The intersubject coefficients of variation after PBMC (43%) and IMC (42%) were similar. CONCLUSION: The myocardial VT of (123)I-mIBG was established in healthy humans for the first time. Accurate kinetic modeling of (123)I-mIBG requires both BPR and metabolite corrections. Population-based BPR correction and metabolite correction curves were developed, allowing more convenient absolute quantification of dynamic (123)I-mIBG SPECT images.

The Association between Nocturnal Cardiac Arrhythmias and Sleep-Disordered Breathing: The DREAM Study.

STUDY OBJECTIVES: To determine whether sleep-disordered breathing (SDB) is associated with cardiac arrhythmia in a clinic-based population with multiple cardiovascular comorbidities and severe SDB. METHODS: This was a cross-sectional analysis of 697 veterans who underwent polysomnography for suspected SDB. SDB was categorized according to the apnea-hypopnea index (AHI): none (AHI < 5), mild (5 ≥ AHI < 15), and moderate-severe (AHI ≥ 15). Nocturnal cardiac arrhythmias consisted of: (1) complex ventricular ectopy, (CVE: non-sustained ventricular tachycardia, bigeminy, trigeminy, or quadrigeminy), (2) combined supraventricular tachycardia, (CST: atrial fibrillation or supraventricular tachycardia), (3) intraventricular conduction delay (ICD), (4) tachyarrhythmias (ventricular and supraventricular), and (5) any cardiac arrhythmia. Unadjusted, adjusted logistic regression, and Cochran-Armitage testing examined the association between SDB and cardiac arrhythmias. Linear regression models explored the association between hypoxia, arousals, and cardiac arrhythmias. RESULTS: Compared to those without SDB, patients with moderate-severe SDB had almost three-fold unadjusted odds of any cardiac arrhythmia (2.94; CI 95%, 2.01-4.30; p < 0.0001), two-fold odds of tachyarrhythmias (2.16; CI 95%,1.47-3.18; p = 0.0011), two-fold odds of CVE (2.01; 1.36-2.96; p = 0.003), and two-fold odds of ICD (2.50; 1.58-3.95; p = 0.001). A linear trend was identified between SDB severity and all cardiac arrhythmia subtypes (p value linear trend < 0.0001). After adjusting for age, BMI, gender, and cardiovascular diseases, moderate-severe SDB patients had twice the odds of having nocturnal cardiac arrhythmias (2.24; 1.48-3.39; p = 0.004). Frequency of obstructive respiratory events and hypoxia were strong predictors of arrhythmia risk. CONCLUSIONS: SDB is independently associated with nocturnal cardiac arrhythmias. Increasing severity of SDB was associated with an increasing risk for any cardiac arrhythmia.

Effect of acetylcholinesterase inhibition with pyridostigmine on cardiac parasympathetic function in sedentary adults and trained athletes.

Heart rate variability and postexercise heart rate recovery are used to assess cardiac parasympathetic tone in human studies, but in some cases these indexes appear to yield discordant information. We utilized pyridostigmine, an acetylcholinesterase inhibitor that selectively augments the parasympathetic efferent signal, to further characterize parasympathetic regulation of rest and postexercise heart rate. We measured time- and frequency-domain indexes of resting heart rate variability and postexercise heart rate recovery in 10 sedentary adults and 10 aerobically trained athletes after a single oral dose of pyridostigmine (30 mg) and matching placebo in randomized, double-blind, crossover trial. In sedentary adults, pyridostigmine decreased resting heart rate [from 66.7 (SD 12.6) to 58.1 beats/min (SD 7.6), P = 0.005 vs. placebo] and increased postexercise heart rate recovery at 1 min [from 40.7 (SD 10.9) to 45.1 beats/min (SD 8.8), P = 0.02 vs. placebo]. In trained athletes, pyridostigmine did not change resting heart rate or postexercise heart rate recovery when compared with placebo. Time- and frequency-domain indexes of resting heart rate variability did not differ after pyridostigmine versus placebo in either cohort and were not significantly associated with postexercise heart rate recovery in either cohort. The divergent effects of pyridostigmine on resting and postexercise measures of cardiac parasympathetic function in sedentary subjects confirm that these measures characterize distinct aspects of cardiac parasympathetic regulation. The lesser effect of pyridostigmine on either measure of cardiac parasympathetic tone in the trained athletes indicates that the enhanced parasympathetic tone associated with exercise training is at least partially attributable to adaptations in the efferent parasympathetic pathway.