Sarcoidosis-Related Cardiomyopathy: Current Knowledge, Challenges, and Future Perspectives State-of-the-Art Review.

The prevalence of sarcoidosis-related cardiomyopathy is increasing. Sarcoidosis impacts cardiac function through granulomatous infiltration of the heart, resulting in conduction disease, arrhythmia, and/or heart failure. The diagnosis of cardiac sarcoidosis (CS) can be challenging and requires clinician awareness as well as differentiation from overlapping diagnostic phenotypes, such as other forms of myocarditis and arrhythmogenic cardiomyopathy. Clinical manifestations, extracardiac involvement, histopathology, and advanced cardiac imaging can all lend support to a diagnosis of CS. The mainstay of therapy for CS is immunosuppression; however, no prospective clinical trials exist to guide management. Patients may progress to developing advanced heart failure or ventricular arrhythmia, for which ventricular assist device therapies or heart transplantation may be considered. The existing knowledge gaps in CS call for an interdisciplinary approach to both patient care and future investigation to improve mechanistic understanding and therapeutic strategies.

Management of heart failure in cardiac amyloidosis using an ambulatory diuresis clinic.

BACKGROUND: Recurrent congestion in cardiac amyloidosis (CA) remains a management challenge, often requiring high dose diuretics and frequent hospitalizations. Innovative outpatient strategies are needed to effectively manage heart failure (HF) in patients with CA. Ambulatory diuresis has not been well studied in restrictive cardiomyopathy. Therefore, we aimed to examine the outcomes of an ambulatory diuresis clinic in the management of congestion related to CA. METHODS AND RESULTS: We retrospectively studied patients with CA seen in an outpatient HF disease management clinic for (1) safety outcomes of ambulatory intravenous (IV) diuresis and (2) health care utilization. Forty-four patients with CA were seen in the clinic a total of 203 times over 6 months. Oral diuretics were titrated at 96 (47%) visits. IV diuretics were administered at 56 (28%) visits to 17 patients. There were no episodes of severe acute kidney injury or symptomatic hypotension. There was a significant decrease in emergency department and inpatient visits and associated charges after index visit to the clinic. The proportion of days hospitalized per 1000 patient days of follow-up decreased as early as 30 days (147.3 vs 18.1/1000 patient days of follow-up, P< .001) and persisted through 180 days (33.6 vs 22.9/1000 patient days of follow-up, P< .001) pre- vs post-index visit to the clinic. CONCLUSIONS: We demonstrate the feasibility of ambulatory IV diuresis in patients with CA. Our findings also suggest that use of a HF disease management clinic may reduce acute care utilization in patients with CA. Leveraging multidisciplinary outpatient HF clinics may be an effective alternative to hospitalization in patients with HF due to CA, a population who otherwise carries a poor prognosis and contributes to high health care burden.

Management of Cardiac Sarcoidosis Using Mycophenolate Mofetil as a Steroid-Sparing Agent.

BACKGROUND: Cardiac sarcoidosis (CS) is a major cause of morbidity and mortality in patients with systemic sarcoidosis. Steroid-sparing agents are increasingly used, despite a lack of randomized trials or published guidelines to direct treatment. METHODS AND RESULTS: This retrospective study included 77 patients with CS treated with prednisone monotherapy (n = 32) or a combination with mycophenolate mofetil (n = 45) between 2003 and 2018. Baseline characteristics and clinical outcomes were evaluated. The mean patient age was 53 ± 11 years at CS diagnosis, 66.2% were male, and 35.1% were Black. The total exposure to maximum prednisone dose (initial prednisone dose × days at dose) was lower in the combination therapy group (1440 mg [interquartile range (IQR), 1200-2760 mg] vs 2710 mg [IQR, 1200-5080 mg]; P = .06). On 18F-fluorodeoxyglucose positron emission tomography scans, both groups demonstrated a significant decrease in the cardiac maximum standardized uptake value after treatment: a median decrease of 3.9 (IQR 2.7-9.0, P = .002) and 2.9 (IQR 0-5.0, P = .001) for prednisone monotherapy and combination therapy, respectively. Most patients experienced improvement or complete resolution in qualitative cardiac 18F-fluorodeoxyglucose uptake (92.3% and 70.4% for the prednisone and combination therapy groups, respectively). Mycophenolate mofetil was well tolerated. CONCLUSIONS: Mycophenolate mofetil in combination with prednisone for the treatment of CS may minimize corticosteroid exposure and decrease cardiac inflammation without significant adverse effects.

The Impact of an Antithrombotic Stewardship Program on Heparin-Induced Thrombocytopenia Management.

Background: An antithrombotic stewardship program was implemented to reduce IV DTI use and increase fondaparinux and direct oral anticoagulant (DOAC) use for suspected or confirmed Heparin-induced thrombocytopenia (HIT). Objectives: This study evaluated the impact of an antithrombotic stewardship program on IV DTI utilization in patients with HIT. Methods: A retrospective analysis of adults receiving IV DTIs or fondaparinux from July 2016 to July 2017 (pre-stewardship) and October 2017 to July 2019 (post-stewardship) was conducted. Results: The median duration of IV DTI administration was not significantly different in HIT-negative patients between the pre- and post-stewardship cohorts (1.6 days (25th percentile (p25), 75th percentile (p75): .5, 3.3) vs 1.7 days (p25, p75: .9, 3.9), P = .31). The median duration of IV DTI administration in HIT-positive patients was 9.9 days (p25, p75: 7.6, 21.0) pre-stewardship and 7.3 days (p25, p75: 4.8, 16.5) post-stewardship (P = .18). For HIT-positive patients, the time from HIT diagnosis to discharge was 12.8 days (p25, p75: 8.9, 24.9) and 9.2 days (p25, p75: 4.0, 18.1) in the pre- and post-stewardship cohorts, respectively (P = .07). Fondaparinux and DOAC prescribing rates were 40.7% and 62.2% in the pre- and post-stewardship cohorts, respectively (P = .09). The percentage of patients with no contraindications to IV DTI alternatives receiving these agents increased from 31.2% to 78.6% (P = .01) following stewardship implementation. Conclusions: Intravenous DTI alternative utilization increased significantly after stewardship implementation. Stewardship implementation was associated with a non-statistically significant trend towards decreased IV DTI utilization and decreased length of stay for HIT-positive patients.

Assisted versus referred pharmacy smoking interventions for patients with thoracic malignancies or pulmonary nodules.

BACKGROUND: Tobacco use is the foremost preventable cause of death, disease, and disability in the United States. Continued tobacco use in malignant disease contributes to treatment failure and disease progression. Pharmacists are pivotal to tobacco cessation counseling, management, and follow up. METHODS: This retrospective, observational, single-center, cohort study of ambulatory cancer patients was designed to assess the impact of assisted versus "Ask, Advise, Refer" (AAR) pharmacy-driven smoking cessation interventions on patient-reported quit rates at 30- and 90-days. Those included were currently smoking or recently quit adults with a thoracic malignancy or nodule. Those in the assisted intervention were offered nicotine replacement therapy (NRT) for free according to a personalized quit plan. After July 1, 2020, patients were enrolled in the AAR intervention, whereby participants were referred to obtain NRT through insurance or external resources. Both clinical interventions were provided as standard of care. RESULTS: 129 participants were included (assisted n = 83; AAR n = 46) with baseline characteristics evenly matched. After excluding those unable to be reached at 30-days, 30 (44.8%) in the assisted intervention quit smoking versus 11 (27.5%) in the AAR intervention, p = 0.08. Lung cancer patients were more likely to report quitting at 30-days in the assisted intervention, 16 (64.0%) versus 5 (29.4%) in the AAR intervention, p = 0.03. After excluding those unable to be reached at 90-days, 30 (45.5%) in the assisted intervention quit versus 11 (35.5%) in the AAR intervention, p = 0.35. CONCLUSIONS: Pharmacy-led smoking cessation initiatives that include providing NRT are especially impactful on smoking cessation in lung cancer patients.

Comparison of Clinical Scoring Tools to Predict Heparin-Induced Thrombocytopenia in Cardiac Surgery.

The 4Ts and HIT-Expert Probability (HEP) scoring tools for heparin-induced thrombocytopenia (HIT) have not been validated in cardiac surgery patients, and the reported sensitivity and specificity of the Post-Cardiopulmonary Bypass (CPB) scoring tool vary widely in the 2 available analyses. It remains unclear which of the available scoring tools most accurately predicts HIT in this population. Forty-nine HIT-positive patients who underwent on-pump cardiac surgery within a 6-year period were loosely matched to 98 HIT-negative patients in a 1:2 case-control design. The 4Ts, HEP, and CPB scores were calculated for each patient. Sensitivity and specificity of each tool were calculated using standard cut-offs. The Youden method was utilized to determine optimal cut-offs within receiver operating characteristic (ROC) curves of each score, after which sensitivities and specificities were recalculated. Using standard cut-offs, the sensitivities for the CPB, HEP, and 4Ts scores were 100%, 93.9%, and 69.4%, respectively. Specificities were 51%, 49%, and 71.4%, respectively. The AUC of the scoring tool ROC curves were 0.961 for the CPB score, 0.773 for the HEP score, and 0.805 for the 4Ts score. Using the Youden method-derived optimal cut-off of  ≥3 points on the CPB score, sensitivity remained 100% with improved specificity to 88.9%. The CPB score is the preferred HIT clinical scoring tool in adult cardiac surgery patients, whereas the 4Ts score performed less effectively. A cut-off of ≥ 3 points on the CPB score could increase specificity while preserving high sensitivity, which should be validated in a prospective evaluation.

Effect of Corticosteroids on Left Ventricular Function in Patients With Cardiac Sarcoidosis.

Cardiac sarcoidosis (CS) is an important cause of cardiomyopathy. The trajectory of left ventricular ejection fraction (LVEF) in patients with CS undergoing treatment remains unclear. Patients with CS who were treated with corticosteroids and who underwent transthoracic echocardiography were studied. Baseline characteristics, treatment, echocardiographic data (including baseline to follow-up change in LVEF), and outcomes were retrospectively evaluated. Among 100 patients, 55 had baseline reduced LVEF (<50%), and 45 had preserved LVEF (≥50%). At follow-up, 82% of patients demonstrated stable or improved LVEF. Change in LVEF was significantly higher in the baseline reduced than in the preserved LVEF group (5% [interquartile range 0 to 15] vs 0% [interquartile range -10% to 5%], p = 0.001). There was no difference in corticosteroid exposure or use of heart failure guideline-directed medical therapy between patients who did experience improvement in LVEF and those who did not experience improvement in LVEF. On multivariable analysis, baseline reduced LVEF (Odds ratio 54.89, 95% confidence interval 3.84 to 785.09, p = 0.003) and complete heart block (Odds ratio 28.88, 95% confidence interval 2.17 to 383.74, p = 0.011) at presentation were significantly associated with reduced LVEF after treatment. In conclusion, most patients with CS treated with corticosteroids maintain or improve LV systolic function. Cardiac characteristics at presentation impact prognosis in CS, despite treatment.

Association of Heparin Dose, Route, Timing, and Duration With Heparin-Induced Thrombocytopenia.

BACKGROUND: The prevalence of heparin-induced thrombocytopenia (HIT) varies by population and the type and duration of heparinoid exposure; however, the association with unfractionated heparin (UFH) dose, route, timing, and duration has not been evaluated in cardiac surgery patients. METHODS: A retrospective case-control study matched HIT-positive adult cardiac surgery patients (positive platelet factor 4 immunoglobulin G and serotonin release assays) 1:1 with HIT-negative controls. Total UFH dose, route, timing, and duration were compared between groups. RESULTS: The study included 124 patients, 92 male (74%), with mean age of 65 ± 11 years. Significantly more HIT-positive patients received intravenous UFH preoperatively or postoperatively compared with patients without HIT (55 [88.7%] vs 23 [37.1%]; P < .001). There were no significant differences regarding intraoperative or subcutaneous UFH dose or duration. When controlling for obesity and cardiopulmonary bypass duration using multivariable conditional logistic regression, the odds of HIT were increased 10-fold in patients who received preoperative or postoperative intravenous UFH continuous infusion (odds ratio 10.2, 95% confidence interval, 3.1 to 33.7; P < .001). Receiver-operating characteristic curves demonstrated that receiving preoperative or postoperative intravenous UFH infusion total dose greater than 32,000 units (sensitivity 82%, specificity 74%, area under the curve 0.78) or longer than 7 hours (sensitivity 87%, specificity 68%, area under the curve 0.77) was associated with HIT. CONCLUSIONS: Odds of HIT were increased 10-fold in adult cardiac surgery patients receiving preoperative or postoperative intravenous UFH infusion. Intraoperative UFH dose and subcutaneous route were not associated with HIT. Future study should evaluate incorporation of intravenous UFH administration, dose, and duration in HIT scoring tools for cardiac surgery patients.

Highest Obesity Category Associated With Largest Decrease in N-Terminal Pro-B-Type Natriuretic Peptide in Patients Hospitalized With Heart Failure With Preserved Ejection Fraction.

Background Heart failure with preserved ejection fraction (HFpEF) constitutes half of hospitalized heart failure cases and is commonly associated with obesity. The role of natriuretic peptide levels in hospitalized obese patients with HFpEF, however, is not well defined. We sought to evaluate change in NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels by obesity category and related clinical outcomes in patients with HFpEF hospitalized for acute heart failure. Methods and Results A total of 89 patients with HFpEF hospitalized with acute decompensated heart failure were stratified into 3 obesity categories: nonobese (body mass index [BMI] <30.0 kg/m2, 19%), obese (BMI 30.0-39.9 kg/m2, 29%), and severely obese (BMI ≥40.0 kg/m2, 52%), and compared for percent change in NT-proBNP during hospitalization and clinical outcomes. Clinical characteristics were compared between patients with normal NT-proBNP (≤125 pg/mL) and elevated NT-proBNP. Admission NT-proBNP was inversely related to BMI category (nonobese, 2607 pg/mL [interquartile range, IQR: 2112-5703]; obese, 1725 pg/mL [IQR: 889-3900]; and severely obese, 770.5 pg/mL [IQR: 128-1268]; P<0.01). Severely obese patients had the largest percent change in NT-proBNP with diuresis (-64.8% [95% CI, -85.4 to -38.9] versus obese -40.4% [95% CI, -74.3 to -12.0] versus nonobese -46.9% [95% CI, -57.8 to -37.4]; P=0.03). Nonobese and obese patients had significantly worse 1-year survival compared with severely obese patients (63% versus 76% versus 95%, respectively; P<0.01). Patients with normal NT-proBNP (13%) were younger, with higher BMI, less atrial fibrillation, and less structural heart disease than those with elevated NT-proBNP. Conclusions In hospitalized patients with HFpEF, NT-proBNP was inversely related to BMI with the largest decrease in NT-proBNP seen in the highest obesity category. These findings have implications for the role of NT-proBNP in the diagnosis and assessment of treatment response in obese patients with HFpEF.

Efficacy of Intravenous Furosemide Versus a Novel, pH-Neutral Furosemide Formulation Administered Subcutaneously in Outpatients With Worsening Heart Failure.

OBJECTIVES: This study sought to determine the efficacy and safety of a novel, pH-neutral formulation of furosemide administered subcutaneously (SC) for treatment of acute decompensated heart failure (HF). BACKGROUND: Congestion requiring intravenous (IV) administration of a diuretic agent is the main reason patients with HF present for acute medical care. METHODS: Outpatients presenting with decompensated HF were randomized to receive a single SC or IV dose of furosemide. Primary outcome was 6-h urine output, and secondary outcomes were weight change, natriuresis, and adverse events. RESULTS: Forty-one patients were randomized: 19 were treated with IV (mean dose: 123 ± 47 mg) and 21 with SC furosemide (fixed dose of 80 mg over 5 h). The 6-h urine output in the IV group was not significantly different from that in the SC furosemide group (median IV: 1,425 ml; interquartile range [IQR]: 1,075 to 1,950 ml; vs. median SC: 1,350 ml; IQR: 900 to 1,900 ml; p = 0.84). Additionally, mean weight loss was not significantly different (-1.5 ± 1.1 kg in the IV group vs. -1.5 ± 1.2 kg in the SC group; p = 0.95). Hourly urine output was significantly higher in the IV group at hour 2 (425 ml in the IV group vs. 250 ml in the SC group; p = 0.02) and higher in the SC group at hour 6 (125 ml, IV group vs. 325 ml, SC group; p = 0.005). Natriuresis was higher in the SC group (IV: 7.3 ± 35.3 mEq/l vs. SC: 32.8 ± 43.6 mEq/l; p = 0.05). There was no worsening renal function, ototoxicity, or skin irritation with either formulation. Thirty-day hospitalization rates were similar. CONCLUSIONS: In this phase II trial, we did not identify significant differences between urine output obtained with pH-neutral furosemide administered SC and that obtained by IV. This method of decongestion may allow treatment at home and reduced HF resources and warrants further investigation. (Sub-Q Versus IV Furosemide in Acute Heart Failure; NCT02579057).

Randomized Evaluation of Heart Failure With Preserved Ejection Fraction Patients With Acute Heart Failure and Dopamine: The ROPA-DOP Trial.

OBJECTIVES: This study sought to compare a continuous infusion diuretic strategy versus an intermittent bolus diuretic strategy, with the addition of low-dose dopamine (3 µg/kg/min) in the treatment of hospitalized patients with heart failure with preserved ejection fraction (HFpEF). BACKGROUND: HFpEF patients are susceptible to development of worsening renal function (WRF) when hospitalized with acute heart failure; however, inpatient treatment strategies to achieve safe and effective diuresis in HFpEF patients have not been studied to date. METHODS: In a prospective, randomized, clinical trial, 90 HFpEF patients hospitalized with acute heart failure were randomized within 24 h of admission to 1 of 4 treatments: 1) intravenous bolus furosemide administered every 12 h; 2) continuous infusion furosemide; 3) intermittent bolus furosemide with low-dose dopamine; and 4) continuous infusion furosemide with low-dose dopamine. The primary endpoint was percent change in creatinine from baseline to 72 h. Linear and logistic regression analyses with tests for interactions between diuretic and dopamine strategies were performed. RESULTS: Compared to intermittent bolus strategy, the continuous infusion strategy was associated with higher percent increase in creatinine (continuous infusion: 16.01%; 95% confidence interval [CI]: 8.58% to 23.45% vs. intermittent bolus: 4.62%; 95% CI: -1.15% to 10.39%; p = 0.02). Low-dose dopamine had no significant effect on percent change in creatinine (low-dose dopamine: 12.79%; 95% CI: 5.66% to 19.92%, vs. no-dopamine: 8.03%; 95% CI: 1.44% to 14.62%; p = 0.33). Continuous infusion was also associated with greater risk of WRF than intermittent bolus (odds ratio [OR]: 4.32; 95% CI: 1.26 to 14.74; p = 0.02); no differences in WRF risk were seen with low-dose dopamine. No significant interaction was seen between diuretic strategy and low-dose dopamine (p > 0.10). CONCLUSIONS: In HFpEF patients hospitalized with acute heart failure, low-dose dopamine had no significant impact on renal function, and a continuous infusion diuretic strategy was associated with renal impairment. (Diuretics and Dopamine in Heart Failure With Preserved Ejection Fraction [ROPA-DOP]; NCT01901809).