Goflikicept and Related IL-1 Inhibitors in the Treatment of Recurrent Pericarditis.

Anticytokine biologics are a promising anti-inflammatory therapy for recurrent pericarditis. Several studies have proved the efficacy and safety of interleukin-1 (IL-1) inhibitors, such as anakinra and rilonacept in patients with recurrent pericarditis. Treatment with goflikicept in a recent phase 2 and 3 trial significantly reduced the pericarditis recurrence rate compared with both the placebo and the allowed withdrawal of standard-of-care therapy. Patients with idiopathic recurrent pericarditis (IRP) achieved remission within the first 14 days of therapy. In rilonacept inhibition of interleukin-1 alpha and beta for recurrent pericarditis (phase 3 trial of interleukin-1 trap rilonacept in recurrent pericarditis), rilonacept led to a significantly lower risk of pericarditis recurrence than placebo (hazard ratio, 0.04; P < 0.001) and a rapid resolution of recurrent pericarditis episodes. However, 74% of patients in the placebo group demonstrated recurrence, compared with 7% in the rilonacept group. The efficacy of anakinra was demonstrated by the AIRTRIP (anakinra-treatment of recurrent idiopathic pericarditis) trial, which showed a reduction in the incidence of recurrent pericarditis in anakinra versus placebo-treated patients (18.2% vs 90%). In patients with recurrences, the mean time to flare was 28.4 days in the placebo group versus 76.5 days in the anakinra group. IL-1 inhibitors require further research and have the potential to decrease the use of first-line drug regimens for recurrent pericarditis that are not tolerated in specific patient groups.

Emerging Therapies for Treatment-Resistant Hypertension: A Review of Lorundrostat and Related Selective Aldosterone Synthase Inhibitors.

The target-hypertension (Target-HTN) trial investigated the efficacy and safety of lorundrostat, an aldosterone synthase inhibitor, as an antihypertensive. Cohort 1 of the trial includes patients with suppressed plasma renin activity and elevated aldosterone levels. Lorundrostat doses of 100 mg and 50 mg daily significantly decreased systolic blood pressure compared to the placebo group. Cohort 2 also demonstrated a reduction in systolic blood pressure with the 100 mg daily dose of lorundrostat. Lorundrostat is more selective for the inhibition of CYP11B2 versus CYP11B1, which makes it preferable to other aldosterone synthase inhibitors that inhibit cortisol synthesis, such as osilodrostat. Phase 3 trials are needed to validate the safety and efficacy of lorundrostat, and further research should be performed on other selective aldosterone synthase inhibitors such as baxdrostat, dexfadrostat, and BI 690517.

A Personalized Cell-Based Therapy for Ischemic Heart Failure With Reduced Ejection Fraction: Safety and Feasibility Outcomes of the Roll-In Cohort of the CardiAMP Cell Therapy Trial and Review of Similar Trials.

CardiAMP Cell Therapy for Heart Failure trial is a prospective, multicenter, randomized, controlled, double-blinded trial that has been granted breakthrough designation by the United States Food and Drug Administration. This trial evaluates clinical outcomes of intramyocardial delivery of a high dose of autologous bone marrow mononuclear cells in chronic postmyocardial infarction heart failure patients. This trial represents the first attempt to personalize marrow-derived cell-based therapy for the treatment of ischemic heart failure with reduced ejection fraction. The roll-in cohort of 10 patients demonstrated improvements in 6-minute walk distance at 6 months (+47.8 m, P = 0.01), 12 months (+46.4 m, P = 0.06), and 24 months (+31 m), and improvements in New York Heart Association class at 3 months (P = 0.015) and 6 months (P = 0.037). Four patients were reduced to New York Heart Association class I at 24 months and Minnesota Living with Heart Failure Questionnaire score was improved in 6 of 10 patients at 24 months. The improved clinical outcomes demonstrated in CardiAMP are consistent with previous clinical trials including the Transendocardial Autologous Cells in Ischemic Heart Failure (TAC-HFT) trial, Prospective Randomized Trial of Direct Endomyocardial Implantation of Bone Marrow Cells for Treatment of Severe Coronary Artery Diseases (PROTECT-CAD), and REGENERATE-Ischemic Heart Disease trial.

Review of the Etiology, Diagnosis, Classification, and Therapy of Right Heart Thrombi.

Right heart thrombi are a rare phenomenon associated with high mortality rates and embolization to the pulmonary bed. Diagnostic modalities include transthoracic echocardiography, contrast-enhanced echocardiography, and cardiac magnetic resonance imaging. Several treatment options for right ventricular thrombus have been described in case reports and observational studies including anticoagulation, thrombolysis, catheter-based procedures, and surgical embolectomy. Various studies have demonstrated that thrombolysis and surgical embolectomy have better survival outcomes than anticoagulation alone. Present management strategies are supported by observational studies, and further research is needed to guide therapy.

Review of the Etiology, Diagnosis, and Therapy of Left Atrial Thrombus.

Thrombi in the left atrial appendage (LAA) are an important cause of systemic thromboembolism in patients with atrial fibrillation. The gold standard for the diagnosis of LAA thrombi is a transesophageal echocardiogram, although cardiac multidetector computed tomography, intracardiac echocardiogram, and cardiac magnetic resonance imaging are alternative diagnostic imaging modalities. When an LAA thrombus is diagnosed, effective anticoagulation is recommended for at least 3 weeks or until thrombus resolution is confirmed on repeat transesophageal echocardiogram. Recent prospective research shows the efficacy of nonvitamin K oral anticoagulants in the treatment of LAA thrombus, which offers a promising alternative to vitamin K antagonists. As an alternative approach, left atrial aspiration thrombectomy has been described in case reports, though there is limited evidence comparing its efficacy to anticoagulation alone.

Review of the Etiology, Diagnosis, and Management of Left Ventricular Thrombus.

The incidence of left ventricular (LV) thrombus following acute myocardial infarction has declined significantly due to recent advancements in reperfusion and antithrombotic therapies. The development of LV thrombus depends on Virchow's triad: endothelial injury following myocardial infarction, blood stasis from LV dysfunction, and hypercoagulability. Diagnostic modalities for LV thrombus include transthoracic echocardiography and late gadolinium enhancement cardiac magnetic resonance imaging. Anticoagulation with direct oral anticoagulants or vitamin K antagonists for 3 months following initial diagnosis of LV thrombus remains the treatment of choice for LV thrombus. However, further evidence is needed to demonstrate the noninferiority of direct oral anticoagulants compared with vitamin K antagonists for the prevention of thromboembolic events.

Change in plasma α-tocopherol associations with attenuated pulmonary function decline and with CYP4F2 missense variation.

BACKGROUND: Vitamin E (vitE) is hypothesized to attenuate age-related decline in pulmonary function. OBJECTIVES: We investigated the association between change in plasma vitE (∆vitE) and pulmonary function decline [forced expiratory volume in the first second (FEV1)] and examined genetic and nongenetic factors associated with ∆vitE. METHODS: We studied 1144 men randomly assigned to vitE in SELECT (Selenium and Vitamin E Cancer Prevention Trial). ∆vitE was the difference between baseline and year 3 vitE concentrations measured with GC-MS. FEV1 was measured longitudinally by spirometry. We genotyped 555 men (vitE-only arm) using the Illumina Expanded Multi-Ethnic Genotyping Array (MEGAex). We used mixed-effects linear regression modeling to examine the ∆vitE-FEV1 association. RESULTS: Higher ∆vitE was associated with lower baseline α-tocopherol (α-TOH), higher baseline γ-tocopherol, higher baseline free cholesterol, European ancestry (as opposed to African) (all P < 0.05), and the minor allele of a missense variant in cytochrome P450 family 4 subfamily F member 2 (CYP4F2) (rs2108622-T; 2.4 µmol/L higher ∆vitE, SE: 0.8 µmol/L; P = 0.0032). Higher ∆vitE was associated with attenuated FEV1 decline, with stronger effects in adherent participants (≥80% of supplements consumed): a statistically significant ∆vitE × time interaction (P = 0.014) indicated that a 1-unit increase in ∆vitE was associated with a 2.2-mL/y attenuation in FEV1 decline (SE: 0.9 mL/y). The effect size for 1 SD higher ∆vitE (+4 µmol/mmol free-cholesterol-adjusted α-TOH) was roughly one-quarter of the effect of 1 y of aging, but in the opposite direction. The ∆vitE-FEV1 association was similar in never smokers (2.4-mL/y attenuated FEV1 decline, SE: 1.0 mL/y; P = 0.017, n = 364), and current smokers (2.8-mL/y, SE: 1.6 mL/y; P = 0.079, n = 214), but there was little to no effect in former smokers (-0.64-mL/y, SE: 0.9 mL/y; P = 0.45, n = 564). CONCLUSIONS: Greater response to vitE supplementation was associated with attenuated FEV1 decline. The response to supplementation differed by rs2108622 such that individuals with the C allele, compared with the T allele, may need a higher dietary intake to reach the same plasma vitE concentration.