Diagnosis and Management of Cardiac Sarcoidosis: A Scientific Statement From the American Heart Association.

Cardiac sarcoidosis is an infiltrative cardiomyopathy that results from granulomatous inflammation of the myocardium and may present with high-grade conduction disease, ventricular arrhythmias, and right or left ventricular dysfunction. Over the past several decades, the prevalence of cardiac sarcoidosis has increased. Definitive histological confirmation is often not possible, so clinicians frequently face uncertainty about the accuracy of diagnosis. Hence, the likelihood of cardiac sarcoidosis should be thought of as a continuum (definite, highly probable, probable, possible, low probability, unlikely) rather than in a binary fashion. Treatment should be initiated in individuals with clinical manifestations and active inflammation in a tiered approach, with corticosteroids as first-line treatment. The lack of randomized clinical trials in cardiac sarcoidosis has led to treatment decisions based on cohort studies and consensus opinions, with substantial variation observed across centers. This scientific statement is intended to guide clinical practice and to facilitate management conformity by providing a framework for the diagnosis and management of cardiac sarcoidosis.

The Association of Unmet Palliative Care Needs and Physical Frailty With Clinical Outcomes: A Prospective Study of Adults With Heart Failure.

BACKGROUND: People with heart failure, particularly those who are physically frail, experience complex needs that can be addressed by palliative care (PC). However, we have a limited understanding of how the intersection of unmet PC needs and physical frailty contributes to health-related quality of life (HRQOL) and risk for hospitalization or mortality. OBJECTIVE: In this study, we sought to examine the association of unmet PC needs and physical frailty with clinical outcomes (baseline HRQOL and hospitalizations or mortality at 6 months). METHODS: We recruited a convenience sample of community-dwelling persons with heart failure from an urban hospital system who were older than 50 years and hospitalized in the last year. We measured physical frailty using the FRAIL scale (nonfrail, 0-2; frail, 3-5), PC needs using the Integrated Palliative Outcome Scale (range, 0-58; higher scores indicating higher needs), and HRQOL using the Kansas City Cardiomyopathy Questionnaire (range, 0-100; higher scores indicate higher HRQOL). We performed multivariable linear regression to test the relationships between physical frailty, PC needs, and HRQOL, and multivariable logistic regression for associations with all-cause 6-month hospitalization or mortality. We also performed an exploratory analysis of 4 PC needs/frailty groups (high PC needs/frail, high PC needs/nonfrail, low PC needs/frail, low PC needs/nonfrail) with outcomes. RESULTS: In our overall sample (n = 298), mean (SD) age was 68 (9.8) years, 37% were women (n = 108), 28% identified as Black/African American (n = 84), and 65% had heart failure with preserved ejection fraction (n = 194). Mean PC needs score was 19.7, and frail participants (n = 130, 44%) had a significantly higher mean PC needs score than nonfrail participants (P < .001). Those with higher PC needs (Integrated Palliative Care Outcome Scale ≥ 20) had significantly worse HRQOL (P < .001) and increased odds of hospitalization or mortality (odds ratio, 2.5; P < .01) compared with those with lower PC needs, adjusting for covariates. Physically frail participants had significantly worse HRQOL (P < .001) and higher odds of hospitalization or mortality at 6 months (odds ratio, 2.6; P < .01) than nonfrail participants, adjusting for covariates. In an exploratory analysis, physically frail participants with high PC needs had the lowest HRQOL score, with an average score of 28.6 points lower (P < .001) and 4.6 times higher odds of hospitalization or mortality (95% confidence interval, 2.03-10.43; P < .001) than low-needs/nonfrail participants. CONCLUSION: Higher unmet PC needs and physical frailty, separately and in combination, were associated with lower HRQOL and higher odds of hospitalization or mortality. Self-reported PC needs and physical frailty assessment in clinical settings may improve identification of patients at the highest risk for poor HRQOL and hospitalization or mortality amenable to PC intervention.

Diagnostic and management strategies in cardiac sarcoidosis.

Cardiac sarcoidosis (CS) is increasingly recognized in the context of with otherwise unexplained electrical or structural heart disease due to improved diagnostic tools and awareness. Therefore, clinicians require improved understanding of this rare but fatal disease to care for these patients. The cardinal features of CS, include arrhythmias, atrio-ventricular conduction delay and cardiomyopathy. In addition to treatments tailored to these cardiac manifestations, immunosuppression plays a key role in active CS management. However, clinical trial and consensus guidelines are limited to guide the use of immunosuppression in these patients. This review aims to provide a practical overview to the current diagnostic challenges, treatment approach, and future opportunities in the field of CS.

Role of genetics in inflammatory cardiomyopathy.

Traditional cardiomyopathy paradigms segregate inflammatory etiologies from those caused by genetic variants. An identified or presumed trigger is implicated in acute myocarditis or chronic inflammatory cardiomyopathy but growing evidence suggests a significant proportion of patients have an underlying cardiomyopathy-associated genetic variant often even when a clear inflammatory trigger is identified. Recognizing a possible genetic contribution to inflammatory cardiomyopathy may have major downstream implications for both the patient and family. The presenting features of myocarditis (i.e. chest pain, arrhythmia, and/or heart failure) may provide insight into diagnostic considerations. One example is isolated cardiac sarcoidosis, a distinct inflammatory cardiomyopathy that carries diagnostic challenges and clinical overlap; genetic testing has increasingly reclassified cases of isolated cardiac sarcoidosis as genetic cardiomyopathy, notably altering management. On the other side, inflammatory presentations of genetic cardiomyopathies are likewise underappreciated and a growing area of investigation. Inflammation plays an important role in the pathogenesis of several familial cardiomyopathies, especially arrhythmogenic phenotypes. Given these clinical scenarios, and the implications on clinical decision making such as initiation of immunosuppression, sudden cardiac death prevention, and family screening, it is important to recognize when genetics may be playing a role.

Occult right ventricular dysfunction and right ventricular-vascular uncoupling in left ventricular assist device recipients.

BACKGROUND: Detecting right heart failure post left ventricular assist device (LVAD) is challenging. Sensitive pressure-volume loop assessments of right ventricle (RV) contractility may improve our appreciation of post-LVAD RV dysfunction. METHODS: Thirteen LVAD patients and 20 reference (non-LVAD) subjects underwent comparison of echocardiographic, right heart cath hemodynamic, and pressure-volume loop-derived assessments of RV contractility using end-systolic elastance (Ees), RV afterload by effective arterial elastance (Ea), and RV-pulmonary arterial coupling (ratio of Ees/Ea). RESULTS: LVAD patients had lower RV Ees (0.20 ± 0.08 vs 0.30 ± 0.15 mm Hg/ml, p = 0.01) and lower RV Ees/Ea (0.37 ± 0.14 vs 1.20 ± 0.54, p < 0.001) versus reference subjects. Low RV Ees correlated with reduced RV septal strain, an indicator of septal contractility, in both the entire cohort (r = 0.68, p = 0.004) as well as the LVAD cohort itself (r = 0.78, p = 0.02). LVAD recipients with low RV Ees/Ea (below the median value) demonstrated more clinical heart failure (71% vs 17%, p = 0.048), driven by an inability to augment RV Ees (0.22 ± 0.11 vs 0.19 ± 0.02 mm Hg/ml, p = 0.95) to accommodate higher RV Ea (0.82 ± 0.38 vs 0.39 ± 0.08 mm Hg/ml, p = 0.002). Pulmonary artery pulsatility index (PAPi) best identified low baseline RV Ees/Ea (≤0.35) in LVAD patients ((area under the curve) AUC = 0.80); during the ramp study, change in PAPi also correlated with change in RV Ees/Ea (r = 0.58, p = 0.04). CONCLUSIONS: LVAD patients demonstrate occult intrinsic RV dysfunction. In the setting of excess RV afterload, LVAD patients lack the RV contractile reserve to maintain ventriculo-vascular coupling. Depression in RV contractility may be related to LVAD left ventricular unloading, which reduces septal contractility.

Management Strategies in Arrhythmogenic Cardiomyopathy across the Spectrum of Ventricular Involvement.

Improved disease recognition through family screening and increased life expectancy with appropriate sudden cardiac death prevention has increased the burden of heart failure in arrhythmogenic cardiomyopathy (ACM). Heart failure management guidelines are well established but primarily focus on left ventricle function. A significant proportion of patients with ACM have predominant or isolated right ventricle (RV) dysfunction. Management of RV dysfunction in ACM lacks evidence but requires special considerations across the spectrum of heart failure regarding the initial diagnosis, subsequent management, monitoring for progression, and end-stage disease management. In this review, we discuss the unique aspects of heart failure management in ACM with a special focus on RV dysfunction.

Noninvasive Point of Care Device for Assessing Cardiac Response to Acute Volume Changes.

Purpose: The change in the amplitude of a peripheral pulse in response to a Valsalva maneuver has diagnostic utility for assessing volume status at the bedside. We have developed a device to automatically quantify the Valsalva pulse response (VPR) to a standardized Valsalva maneuver that the device guides a user to perform. In this study, we sought to determine whether VPR by the device, Indicor, is sensitive enough to detect the acute increase in central pressure and volume load that occurs with a passive leg raise (PLR) in healthy volunteers. Methods: Healthy volunteers were tested semirecumbently at 45 degrees, then again after being leaned back on a pivoted wedge with legs raised at 45 degrees and torso and head flat, and then again in the semirecumbent position. The device recorded a finger photoplethysmography (PPG) signal during a 10-second expiratory effort of 20 mmHg as guided by the device. VPR was automatically calculated as the ratio of the end-Valsalva pulse amplitude to the baseline pulse amplitude. Results: In the 30 participants who completed testing, VPR increased from baseline to PLR in every participant, from 0.34 ± 0.13 to 0.60 ± 0.14 (p < 0.0001). Back upright, VPR decreased back to 0.33 ± 0.10 (p < 0.0001 versus PLR; NS versus baseline position). Conclusion: In this proof-of-concept study of healthy participants, the Indicor device, a noninvasive, convenient device that automatically calculates VPR from a finger photoplethysmography signal during a standardized Valsalva maneuver, was sensitive enough to detect the increase in VPR that occurred with an acute central volume load from a PLR. Future studies should examine whether VPR responds differently to a PLR in heart failure patients with abnormal cardiac performance and/or congestion.

Use of Human-Centered Design Methodology to Develop a Digital Toolkit to Optimize Heart Failure Guideline-Directed Medical Therapy.

BACKGROUND: Guideline-directed medical therapies (GDMTs) improve quality of life and health outcomes for patients with heart failure (HF). However, GDMT utilization is suboptimal among patients with HF. OBJECTIVE: The aims of this study were to engage key stakeholders in semistructured, virtual human-centered design sessions to identify challenges in GDMT optimization posthospitalization and inform the development of a digital toolkit aimed at optimizing HF GDMTs. METHODS: For the human-centered design sessions, we recruited (a) clinicians who care for patients with HF across 3 hospital systems, (b) patients with HF with reduced ejection fraction (ejection fraction ≤ 40%) discharged from the hospital within 30 days of enrollment, and (c) caregivers. All participants were 18 years or older, English speaking, with Internet access. RESULTS: A total of 10 clinicians (median age, 37 years [interquartile range, 35-41], 12 years [interquartile range, 10-14] of experience caring for patients with HF, 80% women, 50% White, 50% nurse practitioners) and three patients and one caregiver (median age 57 years [IQR: 53-60], 75% men, 50% Black, 75% married) were included. Five themes emerged from the clinician sessions on challenges to GDMT optimization (eg, barriers to patient buy-in). Six themes on challenges (eg, managing medications), 4 themes on motivators (eg, regaining independence), and 3 themes on facilitators (eg, social support) to HF management arose from the patient and caregiver sessions. CONCLUSIONS: The clinician, patient, and caregiver insights identified through human-centered design will inform a digital toolkit aimed at optimizing HF GDMTs, including a patient-facing smartphone application and clinician dashboard. This digital toolkit will be evaluated in a multicenter, clinical trial.

Feasibility of a Multi-Component Strengths-Building Intervention for Caregivers of Persons With Heart Failure.

Caregivers of persons with heart failure (HF) navigate complex care plans, yet support strategies often focus solely on meeting the needs of patients. We conducted a randomized waitlist control trial (N = 38) to test the feasibility and gauge initial effect size of the Caregiver Support intervention on quality of life, caregiver burden, and self-efficacy among HF caregivers. The intervention includes up to five remote, nurse-facilitated sessions. Components address: holistic caregiver assessment, life purpose, action planning, resources, and future planning. Caregivers were 93.3% female, 60% White, and 63.3% spouses. Average age was 59.4. Participants who completed the intervention reported high satisfaction and acceptability of activities. Between-group effect sizes at 16 and 32 weeks suggest improvement in quality of life (mental health) (.88; 1.08), caregiver burden (.31; .37), and self-efficacy (.63; .74). Caregivers found Caregiver Support acceptable and feasible. Findings contribute evidence that this intervention can enhance caregiver outcomes. Clinicaltrials.gov Identifier NCT04090749.

The Context of Caregiving in Heart Failure: A Dyadic, Mixed Methods Analysis.

BACKGROUND: Caregiving for persons with heart failure (HF) varies based on the individual, family, and home contexts of the dyad, yet the dyadic context of HF caregiving is poorly understood. OBJECTIVE: The aim of this study was to explore dyadic perspectives on the context of caregiving for persons with HF. METHODS: Family caregivers and persons with HF completed surveys and semistructured interviews. Investigators also photographed caregiving areas to complement home environment data. Descriptive qualitative analysis resulted in 7 contextual domains, and each domain was rated as strength, need, or neutral. We grouped dyads by number of challenging domains of context, categorizing dyads as high (≥3 domains), moderate (1-2 domains), or minimal (0 domains) needs. Quantitative instruments included the 36-item Short Form Health Survey, ENRICHD Social Support, HF Symptom Severity, and Zarit Burden Interview. We applied the average score of each quantitative measure to the groups derived from the qualitative analysis to integrate data in a joint display. RESULTS: The most common strength was the dyadic relationship, and the most challenging domain was caregiving intensity. Every dyad had at least 2 domains of strengths. Of 12 dyads, high-needs dyads (n = 3) had the worst average score for 7 of 10 instruments including caregiver and patient factors. The moderate-needs dyads (n = 6) experienced the lowest caregiver social support and mental health, and the highest burden. CONCLUSION: Strengths and needs were evident in all patient-caregiver dyads with important distinctions in levels of need based on assessment of multiple contextual domains. Comprehensive dyadic and home assessments may improve understanding of unmet needs and improve intervention tailoring.

Sex and Race Differences in Cardiac Sarcoidosis Presentation, Treatment and Outcomes.

BACKGROUND: Although sex- and race-based patterns have been described in the extracardiac organ involvement of sarcoidosis, cardiac sarcoidosis (CS)-specific studies are lacking. METHODS: We studied CS presentation, treatment and outcomes based on sex and race in a tertiary-center cohort. Multivariable adjusted Cox proportional hazards and survival analyses were performed for primary composite outcomes (left ventricular assist device, heart transplantation, all-cause death) and for secondary outcomes (ventricular arrhythmia and all-cause death. RESULTS: We identified 252 patients with CS (108 female, 109 Black). At presentation with CS, females vs males (P = 0.001) and Black vs White individuals (P = 0.001) more commonly had symptomatic heart failure (HF), with HF most common in Black females (ANOVA P < 0.001). Treatment differences included more corticosteroid use (90% vs 79%; P = 0.020), higher 1-year prednisone dosage (13 vs 10 mg; P = 0.003) and less frequent early steroid-sparing agent use in males (29% vs 40%; P = 0.05). Black participants more frequently received a steroid-sparing agent (75% vs 60%; P = 0.023). Composite outcome-free survival did not differ by sex or race. Male sex had an adjusted hazard ratio of 2.34 (95% CI 1.13, 4.80; P = 0.021) for ventricular arrhythmia. CONCLUSION: CS course may differ by sex and race and may contribute to distinct clinical CS phenotypes.

Myocarditis in Patients With Idiopathic Inflammatory Myopathies: Clinical Presentation and Outcomes.

OBJECTIVE: To determine the clinical phenotype and outcomes of patients with idiopathic inflammatory myopathies (IIMs) and myocarditis. METHODS: Using the Johns Hopkins Myositis Center Research Registry, we identified 31 adult patients with IIM-out of a total of 3082 with confirmed or suspected muscle disease-with an encounter code of myocarditis from 2004 to 2021. Of these, 14 adult patients with IIM were adjudicated to have clinical myocarditis. Information about demographics, autoantibodies, and clinical outcomes was retrospectively collected and analyzed. RESULTS: Of 14 patients with IIM with clinical myocarditis, the median age at IIM diagnosis was 49 (IQR 35-56) years, and the median age at myocarditis diagnosis was 54 (IQR 36-61) years. The median duration between IIM diagnosis and myocarditis was 3 (IQR 2-9) years. The majority of patients were female (8/14, 57%) and Black (10/14, 71%). Antisynthetase syndrome was the most common IIM subtype (9/14, 64%). Anti-Jo1 (n = 4) and anti-PL12 (n = 3) were the most frequent autoantibodies. At myocarditis diagnosis, most patients (11/14, 79%) had active myositis, defined as elevated creatine kinase and/or muscle weakness; required hospitalization (13/14, 93%); and had reduced left ventricular ejection fraction (LVEF < 50%; 10/14, 71%). Despite intensification of immunosuppression, the 5-year overall survival rate from IIM diagnosis was 84%, and the 5-year overall survival rate from myocarditis diagnosis was 53%. Systolic dysfunction (LVEF < 40%) at final evaluation was observed in all expired patients (n = 6). CONCLUSION: Clinical presentations of myocarditis in this select cohort of patients with IIM were severe and heterogeneous with poor outcomes despite intensification of immunosuppression, potentially reflecting late detection of myocarditis.

Beyond Stage C: Considerations in the Management of Patients With Heart Failure Progression and Gaps in Evidence.

Despite treatment with contemporary medical therapies for chronic heart failure (HF), there has been an increase in the prevalence of patients progressing to more advanced disease. Patients progressing to and living at the interface of severe stage C and stage D HF are underrepresented in clinical trials, and there is a lack of high-quality evidence to guide clinical decision making. For patients with severe HF phenotypes, the medical therapies used for patients with less advanced stages of illness are often no longer tolerated or provide inadequate clinical stability. The limited data on these patients highlights the need to increase formal research characterizing this high-risk population. This review summarizes existing clinical trial data and incorporates our considerations for approaches to the medical management of patients advanced "beyond stage C" HF.

Palliative Care Needs of Physically Frail Community-Dwelling Older Adults With Heart Failure.

CONTEXT: Physical frailty is emerging as a potential "trigger" for palliative care (PC) consultation, but the PC needs of physically frail persons with heart failure (HF) in the outpatient setting have not been well described. OBJECTIVES: This study describes the PC needs of community dwelling, physically frail persons with HF. METHODS: We included persons with HF ≥50 years old who experienced ≥1 hospitalization in the prior year and excluded those with moderate/severe cognitive impairment, hospice patients, or non-English speaking persons. Measures included the FRAIL scale (0-5: 0 = robust, 1-2 = prefrail, 3-5 = frail) and the Integrated Palliative Outcome Scale (IPOS) (17 items, score 0-68; higher score = higher PC needs). Multiple linear regression tested the association between frailty group and palliative care needs. RESULTS: Participants (N = 286) had a mean age of 68 (range 50-92) were majority male (63%) and White (68%) and averaged two hospitalizations annually. Most were physically frail (44%) or prefrail (41%). Mean PC needs (IPOS) score was 19.7 (range 0-58). On average, participants reported 5.86 (SD 4.28) PC needs affecting them moderately, severely, or overwhelmingly in the last week. Patient-perceived family/friend anxiety (58%) weakness/lack of energy (58%), and shortness of breath (47%) were the most prevalent needs. Frail participants had higher mean PC needs score (26) than prefrail (16, P < 0.001) or robust participants (11, P < 0.001). Frail participants experienced an average of 8.32 (SD 3.72) moderate/severe/overwhelming needs compared to prefrail (4.56, SD 3.77) and robust (2.39, SD 2.91) participants (P < 0.001). Frail participants reported higher prevalence of weakness/lack of energy (83%), shortness of breath (66%), and family/friend anxiety (69%) than prefrail (48%, 39%, 54%) or robust (13%, 14%, 35%) participants (P < 0.001). CONCLUSION: Physically frail people with HF have higher unmet PC needs than those who are nonfrail. Implementing PC needs and frailty assessments may help identify vulnerable patients with unmet needs requiring further assessment and follow-up.

Heterogeneity of Lung Function Phenotypes in Sarcoidosis: Role of Race and Sex Differences.

Rationale: Historically, sarcoidosis was described as a restrictive lung disease, but several alternative phenotypes of pulmonary function have been observed. Pulmonary function phenotypes in sarcoidosis may represent different clinical and/or molecular phenotypes. Objectives: To characterize the prevalence of different pulmonary function phenotypes in a large and diverse sarcoidosis cohort from a tertiary care referral center. Methods: We identified individuals seen between 2005-2015 with a confirmed diagnosis of sarcoidosis. Data were collected from the first pulmonary function test (PFT) performed at our institution which included spirometry and diffusing capacity of the lung for carbon monoxide (DlCO). Demographics and clinical data were collected. Chi-squared analyses and multiple linear regressions were done to assess statistical differences and associations. Global Lung Function Initiative equations were used to calculate percent predicted measurements for spirometry and DlCO. Results: Of 602 individuals with sarcoidosis, 93% (562) had pulmonary involvement, 64% (385) were female, and 57% (341) were Black. Of those with pulmonary involvement, 56% had abnormal pulmonary function. Lung function impairment phenotypes included: 47% restriction, 22% obstruction, 15% isolated reduction in DlCO, and 16% combined obstructive restrictive phenotype. Restriction was the most common PFT phenotype among Black individuals (41%), while no lung impairment was most common among White individuals (66%) (P < 0.001). Males more frequently had obstruction (19%) compared with females (9%) P = 0.001, and females had more restriction (30%) compared with males (21%) P = 0.031. Conclusions: Among individuals with sarcoidosis and pulmonary function impairment, less than half demonstrated a restrictive phenotype. There were significant differences in pulmonary function phenotypes by race and sex.