Arrhythmic manifestations and outcomes of definite and probable cardiac sarcoidosis.

BACKGROUND: The 2014 Heart Rhythm Society consensus statement defines histological (definite) and clinical (probable) diagnostic categories of cardiac sarcoidosis (CS), but few studies have compared their arrhythmic phenotypes and outcomes. OBJECTIVE: The purpose of this study was to evaluate the electrophysiological/arrhythmic phenotype and outcomes of patients with definite and probable CS. METHODS: We analyzed the arrhythmic/electrophysiological phenotype in a single-center North American cohort of 388 patients (median age 56 years; 39% female, n = 151) diagnosed with definite (n = 58) or probable (n = 330) CS (2000-2022). The primary composite outcome was survival to first ventricular tachycardia/fibrillation (VT/VF) event or sudden cardiac death. Key secondary outcomes were also assessed. RESULTS: At index evaluation, in situ cardiac implantable electronic devices and antiarrhythmic drug use were more common in definite CS. At a median follow-up of 3.1 years, the primary outcome occurred in 22 patients with definite CS (38%) and 127 patients with probable CS (38%) (log-rank, P = .55). In multivariable analysis, only a higher ratio of the 18F-fluorodeoxyglucose maximum standardized uptake value of the myocardium to the maximum standardized uptake value of the blood pool (hazard ratio 1.09; 95% confidence interval 1.03-1.15; P = .003, per 1 unit increase) was associated with the primary outcome. During follow-up, patients with definite CS had a higher burden of device-treated VT/VF events (mean 2.86 events per patient-year vs 1.56 events per patient-year) and a higher rate of progression to heart transplant/left ventricular assist device implantation but no difference in all-cause mortality compared with patients with probable CS. CONCLUSION: Patients with definite and probable CS had similarly high risks of first sustained VT/VF/sudden cardiac death and all-cause mortality, though patients with definite CS had a higher overall arrhythmia burden. Both CS diagnostic groups as defined by the 2014 Heart Rhythm Society criteria require an aggressive approach to prevent arrhythmic complications.

Analysis of Cardiac Computed Tomography Anatomy in Patients With Severe Tricuspid Regurgitation Considered for Transcatheter Intervention.

Background: Severe tricuspid regurgitation (TR) is associated with considerable morbidity/mortality in an elderly population with multiple comorbidities. There is interest in transcatheter interventions to manage severe TR. Understanding complex right heart (RH) geometry and tricuspid valve shape and size has implications for patient/device selection for transcatheter intervention. We characterized RH anatomy by computed tomography in patients with symptomatic severe TR considered for intervention. Methods: The retrospective Mayo Clinic study included 29 patients with an echocardiogram and cardiac computed tomography angiogram considered for intervention of severe TR from March 01, 2016 to December 15, 2020. Patients were divided into 2 groups: intervention (surgical or transcatheter; n = 17) and medical management alone (n = 12). Results: Mean age was 83 ± 8 (83% female), 100% had atrial fibrillation, and 62% had chronic kidney disease ≥3a. Ninety-seven percent were symptomatic, 93% had been prescribed loop diuretics, and 24% had device leads. Mean tricuspid annular plane systolic excursion was 16.8 ± 4.5 mm, effective regurgitant orifice area was 81 ± 33 mm2, and cardiac index was 2.6 ± 0.6 L/min/m2. Forty-one percent had at least moderate right ventricular (RV) dysfunction with a mean RV systolic pressure of 46 ± 16 mmHg. Patients receiving intervention had significantly larger effective regurgitant orifice area (101 ± 33 vs. 63 ± 22 mm2, p = 0.033), shorter tricuspid leaflet tenting length (6.5 ± 3.0 vs. 8.9 ± 2.7 mm, p = 0.042), and smaller annuloplasty diagnostic perimeter during diastole (120.1 ± 16.6 vs. 131.1 ± 7.4 mm, p = 0.041). Intervention patients tended to have better right ventricular function, smaller RV and inferior vena cava size, and more severe symptoms. The maximal tricuspid annulus diameter in systole and diastole was 51 ± 5 and 53 ± 7 mm, respectively. Conclusions: Severe TR patients referred for transcatheter intervention present with severe RH enlargement with a large proportion having tricuspid annulus dimensions outside the range for current devices available in clinical trials. The presented data have implications for device development/selection and procedural feasibility.

The Mechanism and Natural History of Mitral Regurgitation in Cardiac Sarcoidosis.

Cardiac sarcoidosis (CS) is an infl/ammatory cardiomyopathy that can present with mitral regurgitation (MR), but few studies describe the mechanisms and natural history of MR in CS. We queried an institutional registry of 512 patients with CS for moderate or greater MR at diagnosis. Baseline demographic and echocardiography (TTE) data were collected. MR was classified by Carpentier type. Positron emission tomography was analyzed for 2-deoxy-2-[fluorine-18] fluoro-d-glucose (FDG) avidity of anterolateral and posteromedial papillary muscles. Follow-up TTE and positron emission tomography imaging of patients treated with immunosuppression was analyzed for MR severity and FDG avidity changes. Fifty-four patients were identified. Mean left ventricular ejection fraction was 39.3%, effective regurgitant orifice 0.34 cm2, and MR regurgitant volume 46.3 ml. Carpentier type I was the most common MR mechanism (46.3%). Forty-one patients had follow-up TTE (median follow-up 1.7 years, interquartile range 2.6 years). Evaluating preprocedural follow-up TTE only, MR severity was significantly reduced, with 37% of patients showing reduction by at least 1 severity grade (p = 0.04). With postprocedural TTE included, 61% of patients showed alleviation of MR severity with mean decrease in grade - 0.98 (p <0.001). Sixty-eight percent of patients had anterolateral/posteromedial FDG avidity. Papillary muscle FDG avidity resolved in 80% of patients (n = 20, median follow-up 1.6 years, interquartile range 2.5 years). In conclusion, Carpentier type I functional MR is the most common MR mechanism in CS. MR severity and papillary muscle FDG avidity decrease after treatment, and MR resolution is further strengthened by procedural intervention in a minority of patients, suggesting an overall favorable natural history of MR in CS.

18F-FDG/13N-ammonia cardiac PET findings in ATTR cardiac amyloidosis.

18F-flurodeoxyglycose (FDG)/13N-ammonia positron emission tomography/computed tomography (PET/CT) is frequently utilized to evaluate cardiac sarcoidosis (CS) but findings can reflect other forms of myocardial inflammation or altered myocardial metabolic activity. Herein, we present five cases where cardiac PET findings suggested CS, but right ventricular endomyocardial biopsy samples revealed ATTR-type cardiac amyloidosis.

Incidence of Preclinical Heart Failure in a Community Population.

Background A high prevalence of preclinical heart failure (HF) (Stages A and B) has previously been shown. The aim of this study was to explore factors associated with the incidence of preclinical HF in a community population. Methods and Results Retrospective review of 393 healthy community individuals aged ≥45 years from the Olmsted County Heart Function Study that returned for 2 visits, 4 years apart. At visit 2, individuals that remained normal were compared with those that developed preclinical HF. By the second visit, 191 (49%) developed preclinical HF (12.1 cases per 100 person-years of follow-up); 65 (34%) Stage A and 126 (66%) Stage B. Those that developed preclinical HF (n=191) were older (P=0.004), had a higher body mass index (P<0.001), and increased left ventricular mass index (P=0.006). When evaluated separately, increased body mass index was seen with development of Stage A (P<0.001) or Stage B (P=0.009). Echocardiographic markers of diastolic function were statistically different in those that developed Stage A [higher E/e' (P<0.001), lower e' (P<0.001)] and Stage B [higher left atrial volume index (P<0.001), higher E/e' (P<0.001), lower e' (P<0.001)]. NT-proBNP (N-terminal pro-B-type natriuretic peptide) was higher at visit 2 in those that developed Stage A or B (P<0.001 for both). Hypertension (57%), obesity (34%), and hyperlipidemia (25%) were common in the development of Stage A. Of patients who developed Stage B, 71% (n=84) had moderate or severe diastolic dysfunction. Conclusions There is a high incidence of preclinical HF in a community population. Development of Stage A was driven by hypertension and obesity, while preclinical diastolic dysfunction was seen commonly in those that developed Stage B.

Serial Left and Right Ventricular Strain Analysis in Patients Recovered from COVID-19.

BACKGROUND: Strain analysis of transthoracic echocardiography (TTE) is a sensitive tool to detect myocardial dysfunction in those affected by COVID-19. Consideration of preexisting cardiovascular disease is important in detecting changes related to COVID-19. We sought to assess serial TTE changes in patients recovered from COVID-19 compared with baseline, pre-COVID-19 exams, with a focus on left and right ventricular longitudinal strain. METHODS: This retrospective review of serial TTEs in confirmed COVID-19 patients at Mayo Clinic sites included patients who had a TTE within 2 years prior to confirmed COVID-19 diagnosis, and the first available outpatient TTE after diagnosis was used as a comparison. Patients with interval cardiac surgery, procedure, or device placement (n = 9) were excluded. Biventricular strain was retrospectively performed on both echocardiograms. RESULTS: Of 259 individuals, ages 60 ± 16 years, 47% female, and 88% Caucasian, post-COVID-19 TTEs were performed a median of 55 days (interquartile range, 37-92) following diagnosis. No clinically significant TTE changes were noted, although left ventricular ejection fraction was higher (58% vs 57%, P = .049) and tricuspid annulus plane systolic excursion was lower (20 vs 21 mm, P = .046) following COVID-19. Baseline left ventricular global longitudinal strain (LV GLS) and right ventricular free wall strain (RV FWS) were normal (-19.6% and -25.8%, respectively) and similar following COVID-19 (-19.6% and -25.7%, P = .07 and .77, respectively). In the 74 inpatients, no significant change from baseline was seen for LV GLS (-19.4% vs -19.1%, P = .62), RV FWS (-25.5% vs -25.0%, P = .69), or left ventricular ejection fraction (57% vs 57%, P = .71). A significant worsening in strain occurred in 27 patients, 16 (6.8%) of the 237 with LV GLS and 14 (6.0%) of the 235 with RV FWS. Ten (20%) patients reporting new symptoms following COVID-19 had worsened strain, compared with 5 (7%) with persistent/progressive symptoms and 11 (9%) with no new symptoms (P = .04). CONCLUSIONS: While patients with new symptoms following COVID-19 were more likely to have a worsening in absolute strain values, no clinically significant change in TTE parameters was evident in most patients following COVID-19 regardless of symptom status.

PET Imaging in Cardiac Sarcoidosis: A Narrative Review with Focus on Novel PET Tracers.

Sarcoidosis is a multi-system inflammatory disease characterized by the development of inflammation and noncaseating granulomas that can involve nearly every organ system, with a predilection for the pulmonary system. Cardiac involvement of sarcoidosis (CS) occurs in up to 70% of cases, and accounts for a significant share of sarcoid-related mortality. The clinical presentation of CS can range from absence of symptoms to conduction abnormalities, heart failure, arrhythmias, valvular disease, and sudden cardiac death. Given the significant morbidity and mortality associated with CS, timely diagnosis is important. Traditional imaging modalities and histologic evaluation by endomyocardial biopsy often provide a low diagnostic yield. Cardiac positron emission tomography (PET) has emerged as a leading advanced imaging modality for the diagnosis and management of CS. This review article will summarize several aspects of the current use of PET in CS, including indications for use, patient preparation, image acquisition and interpretation, diagnostic and prognostic performance, and evaluation of treatment response. Additionally, this review will discuss novel PET radiotracers currently under study or of potential interest in CS.

Progression of Preclinical Heart Failure: A Description of Stage A and B Heart Failure in a Community Population.

BACKGROUND: The aims of this study are to evaluate the rate of progression of preclinical (Stage A and B) heart failure, identify associated characteristics, and evaluate long-term outcomes. METHODS: Retrospective review of the Olmsted County Heart Function Study. Individuals categorized as Stage A or B heart failure at initial visit that returned for a second visit 4 years later were included. Logistic regression analyses evaluated group differences with adjustment for age and sex. RESULTS: At visit 1, 413 (32%) individuals were classified as Stage A and 413 (32%) as Stage B. By visit 2, 146 (35%) individuals from Stage A progressed with the vast majority (n=142) progressing to Stage B. In comparison, a total of 23 (6%) individuals progressed from Stage B. A greater rate of progression was seen for Stage A compared with Stage B (8.7 per 100 person-years [95% CI, 7.4-10.2] versus 1.4 per 100 person-years [95% CI, 0.9-2.1]; P<0.001). NT-proBNP correlated with progression for Stage B (P=0.01), but not for Stage A (P=0.39). A multivariate model found female sex (odds ratio, 1.65 [95% CI, 1.05-2.58]; P=0.03), increased E/e' (odds ratio, 1.13 [95% CI, 1.02-1.26], P=0.02), and beta blocker use (odds ratio, 2.19 [95% CI, 1.25-3.82], P=0.006) were associated with progression for Stage A. There was a signal that cardiovascular mortality was higher in individuals who progressed, although not statistically significant (P=0.06 for Stage A and P=0.05 for Stage B). CONCLUSIONS: There is significant progression of preclinical heart failure in a community population, with progression rates higher for Stage A. NT-proBNP correlated with progression for Stage B, but not for Stage A. No statistically significant differences in long-term outcomes were seen. Study results have clinical implications important to help guide future heart failure screening and prevention strategies.

Association of Pregnancy With Recurrence of Spontaneous Coronary Artery Dissection Among Women With Prior Coronary Artery Dissection.

Importance: Spontaneous coronary artery dissection (SCAD) is a notable cause of acute coronary syndrome in women of childbearing age. Objective: To test the hypothesis that pregnancy after SCAD is associated with recurrent SCAD. Design, Setting, and Participants: Three study designs were implemented: a case series of women with pregnancy after SCAD; a nested case-control study comparing patients with recurrent SCAD to matched controls without recurrent SCAD; and a cohort study. Women with SCAD who were of childbearing potential and enrolled into the Mayo Clinic SCAD Registry from August 30, 2011, to April 4, 2019, were included in the study. Patients with coronary dissections associated with iatrogenesis, trauma, or atherosclerosis were not enrolled. Exposures: Pregnancy after SCAD. Main Outcomes and Measures: The primary outcome was SCAD recurrence, defined as an acute coronary syndrome or cardiac arrest due to new SCAD. Other demographic measures collected included age, year of SCAD occurrence, and comorbidities. Results: The cohort included 636 women of childbearing potential. Twenty-three of those women had a total of 32 pregnancies after SCAD. The median (interquartile range) age of women with pregnancy after SCAD was 38 years (34-40 years), and 20 (87%) were White. In the nested case-control study, 92 cases of recurrent SCAD were matched to 158 controls. There was no significant difference in exposure to subsequent pregnancies in the women with recurrent SCAD as compared with matched controls (2 of 92 [2%] vs 13 of 158 [8%]; P = .06). In the overall cohort of 636 patients, recurrent SCAD was present in 122 patients with a Kaplan-Meier 5-year SCAD recurrence estimate of 14.8%. The Cox analysis showed no significant association between subsequent pregnancy and SCAD recurrence with a nonsignificant hazard ratio of 0.38 (95% CI, 0.09-1.6) when controlling for age at first SCAD, year of first SCAD, and fibromuscular dysplasia. Conclusions and Relevance: This study found that most women tolerated pregnancy and lactation after SCAD without evidence for increased risk of SCAD recurrence when compared with women with a history of SCAD who did not experience pregnancy. Although this study is reassuring and indicates complex contributors to SCAD recurrence, the results need to be interpreted prudently because of study selection bias and the small total number of women who became pregnant after SCAD. The notable hemodynamic changes that occur with pregnancy and severe presentation of pregnancy-associated SCAD are reasons for concern when considering pregnancy after SCAD.

End-of-Life Discussions in Patients With Heart Failure.

BACKGROUND: Although guidelines call on clinicians to conduct regular conversations about advance care planning and end-of-life (EOL) preferences with patients with heart failure (HF), research suggests that physicians often avoid these discussions. METHODS AND RESULTS: From January 20, 2014, to January 18, 2016, Southeastern Minnesota residents hospitalized with acute decompensated HF (ADHF) at Mayo Clinic hospitals were enrolled into an observational cohort study that included the administration of face-to-face questionnaires. Risk of death (prognosis) was estimated using the Meta-analysis Global Group in Chronic Heart Failure score. Among 400 patients (mean age 77.7 years, 46% female, 48% preserved ejection fraction), only 69 (17%) reported previously discussing EOL wishes with their physician. Patients reporting EOL discussions more often had an advance directive (81% vs 66%; P = .009), recognized the term "hospice" (96% vs 87%; P = .027), and had more favorable attitudes of dying and hospice (P = .030). Resuscitation preferences and rates of completion of advance directives varied with prognosis, although patient-clinician EOL discussions did not. CONCLUSIONS: The majority of patients hospitalized with ADHF did not recall discussing their preferences for EOL care with their physician. This represents an important modifiable gap in the optimal longitudinal care of HF patients.

Discordance of Patient-Reported and Clinician-Ordered Resuscitation Status in Patients Hospitalized With Acute Decompensated Heart Failure.

CONTEXT: Accurate documentation of preferences for cardiopulmonary resuscitation at hospital admission is critical to ensure that patients receive resuscitation or not in accordance with their wishes. OBJECTIVES: We sought to identify and characterize inconsistencies in patient-reported and clinician-ordered resuscitation status in patients hospitalized with acute decompensated heart failure (ADHF). METHODS: Southeastern Minnesota residents hospitalized with ADHF were prospectively enrolled into a study that included the administration of face-to-face questionnaires from January 2014 to February 2016. Patient-reported resuscitation status was assessed at enrollment using a validated question. Clinician-ordered resuscitation preferences at hospital admission were abstracted from the electronic medical record. RESULTS: Of the 400 patients administered the questionnaire; 213 (53.3%) stated their resuscitation preference as Full Code, 166 (41.5%) do-not-resuscitate (DNR), and 21 (5.3%) were unsure. In comparison, clinician-ordered resuscitation status was Full Code in 263 (65.8%) patients, DNR in 133 (33.3%), and not documented in four (1.0%). Patient-reported and clinician-ordered resuscitation status was discordant in 20% of patients, of whom 5.6% elected Full Code by questionnaire and had a DNR clinician order, and 14.4% elected DNR by questionnaire but had a Full Code clinician order. Differences in age, comorbidities, health literacy, marital status, completion of advance directives, hospital length of stay, and discharge destination in patients with discordant vs. concordant resuscitation preferences were observed. CONCLUSIONS: Patient-reported and clinician-ordered resuscitation preferences were discordant in 20% of patients hospitalized with ADHF. The underlying etiology of these inconsistencies may reflect factors such as patient indecisiveness or patient-clinician miscommunication and requires further exploration.

Malondialdehyde-acetaldehyde adducts and anti-malondialdehyde-acetaldehyde antibodies in rheumatoid arthritis.

OBJECTIVE: Malondialdehyde-acetaldehyde (MAA) adducts are a product of oxidative stress associated with tolerance loss in several disease states. This study was undertaken to investigate the presence of MAA adducts and circulating anti-MAA antibodies in patients with rheumatoid arthritis (RA). METHODS: Synovial tissue from patients with RA and patients with osteoarthritis (OA) were examined for the presence of MAA-modified and citrullinated proteins. Anti-MAA antibody isotypes were measured in RA patients (n = 1,720) and healthy controls (n = 80) by enzyme-linked immunosorbent assay. Antigen-specific anti-citrullinated protein antibodies (ACPAs) were measured in RA patients using a multiplex antigen array. Anti-MAA isotype concentrations were compared in a subset of RA patients (n = 80) and matched healthy controls (n = 80). Associations of anti-MAA antibody isotypes with disease characteristics, including ACPA positivity, were examined in all RA patients. RESULTS: Expression of MAA adducts was increased in RA synovial tissue compared to OA synovial tissue, and colocalization with citrullinated proteins was found. Increased levels of anti-MAA antibody isotypes were observed in RA patients compared to controls (P < 0.001). Among RA patients, anti-MAA antibody isotypes were associated with seropositivity for ACPAs and rheumatoid factor (P < 0.001) in addition to select measures of disease activity. Higher anti-MAA antibody concentrations were associated with a greater number of positive antigen-specific ACPA analytes (expressed at high titer) (P < 0.001) and a higher ACPA score (P < 0.001), independent of other covariates. CONCLUSION: MAA adduct formation is increased in RA and appears to result in robust antibody responses that are strongly associated with ACPAs. These results support speculation that MAA formation may be a cofactor that drives tolerance loss, resulting in the autoimmune responses characteristic of RA.