Health-related quality of life in patients with recurrent pericarditis: results from a phase 2 study of rilonacept.

BACKGROUND: Impact of recurrent pericarditis (RP) on patient health-related quality of life (HRQoL) was evaluated through qualitative patient interviews and as an exploratory endpoint in a Phase 2 trial evaluating the efficacy and safety of rilonacept (IL-1α/IL-1ß cytokine trap) to treat RP. METHODS: Qualitative interviews were conducted with ten adults with RP to understand symptoms and HRQoL impacts, and the 10-item Patient-Reported Outcomes Measurement Information System Global Health (PROMIS GH) v1.2 was evaluated to determine questionnaire coverage of patient experience. The Phase 2 trial enrolled participants with active symptomatic RP (A-RP, n = 16) and corticosteroid-dependent participants with no active recurrence at baseline (CSD-RP, n = 9). All participants received rilonacept weekly during a 6-week base treatment period (TP) plus an optional 18-week extension period (EP). Tapering of concomitant medications, including corticosteroids (CS), was permitted during EP. HRQoL was assessed using the PROMIS GH, and patient-reported pain and blood levels of c-reactive protein (CRP) were collected at Baseline and follow-up periods. A secondary, descriptive analysis of the Phase 2 trial efficacy results was completed using HRQoL measures to characterize both the impact of RP and the treatment effect of rilonacept. RESULTS: Information from qualitative interviews demonstrated that PROMIS GH concepts are relevant to adults with RP. From the Phase 2 trial, both participant groups showed impacted HRQoL at Baseline (mean PROMIS Global Physical Health [GPH] and Global Mental Health [GMH], were lower than population norm average). In A-RP, GPH/MPH improved by end of base TP and were sustained through EP (similar trends were observed for pain and CRP). Similarly, in CSD-RP, GPH/MPH improved by end of TP and further improved during EP, during CS tapering or discontinuation, without disease recurrence (low pain scores and CRP levels continued during the TP and EP). CONCLUSION: This is the first study demonstrating impaired HRQoL in RP. Rilonacept treatment was associated with HRQoL improvements using PROMIS GH scores. Maintained/improved HRQoL during tapering/withdrawal of CS without recurrence suggests that rilonacept may provide an alternative to CS. TRIAL REGISTRATION: ClinicalTrials.Gov; NCT03980522; 5 June 2019, retrospectively registered; https://clinicaltrials.gov/ct2/show/NCT03980522 .

Increased myocardial extracellular volume in active idiopathic systemic capillary leak syndrome.

BACKGROUND: The Systemic Capillary Leak Syndrome (SCLS) is a rare disorder of unknown etiology presenting as recurrent episodes of shock and peripheral edema due to leakage of fluid into soft tissues. Insights into SCLS pathogenesis are few due to the scarcity of cases, and the etiology of vascular barrier disruption in SCLS is unknown. Recent advances in cardiovascular magnetic resonance (CMR) allow for the quantitative assessment of the myocardial extracellular volume (ECV), which can be increased in conditions causing myocardial edema. We hypothesized that measurement of myocardial ECV may detect myocardial vascular leak in patients with SCLS. METHODS: Fifty-six subjects underwent a standard CMR examination at the NIH Clinical Center from 2009 until 2014: 20 patients with acute intermittent SCLS, six subjects with chronic SCLS, and 30 unaffected controls. Standard volumetric measurements; late gadolinium enhancement imaging and pre- and post-contrast T1 mapping were performed. ECV was calculated by calibration of pre- and post-contrast T1 values with blood hematocrit. RESULTS: Demographics and cardiac parameters were similar in both groups. There was no significant valvular disorder in either group. Subjects with chronic SCLS had higher pre-contrast myocardial T1 compared to healthy controls (T1: 1027 ± 44 v. 971 ± 41, respectively; p = 0.03) and higher myocardial ECV than patients with acute intermittent SCLS or controls: 33.8 ± 4.6, 26.9 ± 2.6, 26 ± 2.4, respectively; p = 0.007 v. acute intermittent; P = 0.0005 v. controls). When patients with chronic disease were analyzed together with five patients with acute intermittent disease who had just experienced an acute SCLS flare, ECV values were significantly higher than in subjects with acute intermittent SCLS in remission or age-matched controls and (31.2 ± 4.6 %, 26.5 ± 2.7 %, 26 ± 2.4 %, respectively; p = 0.01 v. remission, p = 0.001 v. controls). By contrast, T1 values did not distinguish these three subgroups (1008 ± 40, 978 ± 40, 971 ± 41, respectively, p = 0.2, active v. remission; p = 0.06 active v. controls). Abundant myocardial edema without evidence of acute inflammation was detected in cardiac tissue postmortem in one patient. CONCLUSIONS: Patients with active SCLS have significantly higher myocardial ECV than age-matched controls or SCLS patients in remission, which correlated with histopathological findings in one patient.

Myocardial infarction due to intracoronary embolization of percutaneous coronary intervention packaging.

Intracoronary device loss is occasionally encountered and removal is commonly performed at the time of the procedure. We report a case of removal of a retained coronary balloon protective plastic tubing inadvertently left in the coronary artery for a month and associated with myocardial infarction. Optical coherence tomography was used to visualize the foreign body prior to removal with a snare. To our knowledge this is the first report of a removal of disposable packaging equipment after prolonged intracoronary dwell time.

Assessment of global myocardial perfusion reserve using cardiovascular magnetic resonance of coronary sinus flow at 3 Tesla.

BACKGROUND: Despite increasing clinical use, there is limited data regarding regadenoson in stress perfusion cardiovascular magnetic resonance (CMR). In particular, given its long half-life the optimal stress protocol remains unclear. Although Myocardial Perfusion Reserve (MPR) may provide additive prognostic information, current techniques for its measurement are cumbersome and challenging for routine clinical practice.The aims of this study were: 1) To determine the feasibility of MPR quantification during regadenoson stress CMR by measurement of Coronary Sinus (CS) flow; and 2) to investigate the role of aminophylline reversal during regadenoson stress-CMR. METHODS: 117 consecutive patients with possible myocardial ischemia were prospectively enrolled. Perfusion imaging was performed at 1 minute and 15 minutes after administration of 0.4 mg regadenoson. A subgroup of 41 patients was given aminophylline (100 mg) after stress images were acquired. CS flow was measured using phase-contrast imaging at baseline (pre CS flow), and immediately after the stress (peak CS flow) and rest (post CS flow) perfusion images. RESULTS: CS flow measurements were obtained in 92% of patients with no adverse events. MPR was significantly underestimated when calculated as peak CS flow/post CS flow as compared to peak CS flow/pre CS flow (2.43±0.20 vs. 3.28±0.32, p=0.03). This difference was abolished when aminophylline was administered (3.35±0.44 vs. 3.30±0.52, p=0.95). Impaired MPR (peak CS flow/pre CS flow<2) was associated with advanced age, diabetes, current smoking and higher Framingham risk score. CONCLUSIONS: Regadenoson stress CMR with MPR measurement from CS flow can be successfully performed in most patients. This measurement of MPR appears practical to perform in the clinical setting. Residual hyperemia is still present even 15 minutes after regadenoson administration, at the time of resting-perfusion acquisition, and is completely reversed by aminophylline. Our findings suggest routine aminophylline administration may be required when performing stress CMR with regadenoson.

Impact of cardiovascular magnetic resonance on management and clinical decision-making in heart failure patients.

BACKGROUND: Cardiovascular magnetic resonance (CMR) can provide important diagnostic and prognostic information in patients with heart failure. However, in the current health care environment, use of a new imaging modality like CMR requires evidence for direct additive impact on clinical management. We sought to evaluate the impact of CMR on clinical management and diagnosis in patients with heart failure. METHODS: We prospectively studied 150 consecutive patients with heart failure and an ejection fraction ≤ 50% referred for CMR. Definitions for "significant clinical impact" of CMR were pre-defined and collected directly from medical records and/or from patients. Categories of significant clinical impact included: new diagnosis, medication change, hospital admission/discharge, as well as performance or avoidance of invasive procedures (angiography, revascularization, device therapy or biopsy). RESULTS: Overall, CMR had a significant clinical impact in 65% of patients. This included an entirely new diagnosis in 30% of cases and a change in management in 52%. CMR results directly led to angiography in 9% and to the performance of percutaneous coronary intervention in 7%. In a multivariable model that included clinical and imaging parameters, presence of late gadolinium enhancement (LGE) was the only independent predictor of "significant clinical impact" (OR 6.72, 95% CI 2.56-17.60, p=0.0001). CONCLUSIONS: CMR made a significant additive clinical impact on management, decision-making and diagnosis in 65% of heart failure patients. This additive impact was seen despite universal use of prior echocardiography in this patient group. The presence of LGE was the best independent predictor of significant clinical impact following CMR.

Efficacy and safety of rilonacept for recurrent pericarditis: results from a phase II clinical trial.

OBJECTIVE: Recurrent pericarditis (RP) incurs significant morbidity. Rilonacept inhibits both interleukin-1 alpha (IL-1α) and IL-1ß; these cytokines are thought to play a major role in RP. This phase II study evaluated rilonacept efficacy and safety in RP. METHODS: This multicentre, open-label study enrolled adult patients with idiopathic or postpericardiotomy RP, symptomatic (≥2 pericarditis recurrences) or corticosteroid (CS) dependent (≥2 recurrences prior).Patients received rilonacept 320 mg SC load/160 mg SC weekly maintenance in a 6-week base treatment period (TP) followed by an optional 18-week on-treatment extension period (EP) (option to wean background therapy). RESULTS: Outcomes: pericarditis pain (numeric rating scale (NRS)) and inflammation (C reactive protein (CRP)) for symptomatic patients; disease activity after CS taper for CS-dependent patients. SECONDARY OUTCOMES: health-related quality of life (HRQOL), pericarditis manifestations and additional medications. 25 unique patients enrolled, while 23 completed the EP (seven colchicine failures and five CS failures). In symptomatic patients, NRS and CRP decreased; response was observed after first rilonacept dose. NRS decreased from 4.5 at baseline to 0.7, and CRP decreased from 4.62 mg/dL at baseline to 0.38 mg/dL at end of TP. Median time to CRP normalisation: 9 days. Pericarditis manifestations resolved. 13 patients on CS at baseline completed the EP; 11 (84.6%) discontinued CS, and 2 tapered; CRP and NRS remained low without recurrence. Mean HRQOL scores improved in symptomatic patients. One serious adverse event (SAE) resulted in discontinuation of rilonacept. CONCLUSIONS: Rilonacept led to rapid and sustained improvement in pain, inflammation (CRP and pericarditis manifestations) and HRQOL. CSs were successfully tapered or discontinued; safety was consistent with known rilonacept safety profile. TRIAL REGISTRATION NUMBER: NCT03980522.

Accuracy of predicted orthogonal projection angles for valve deployment during transcatheter aortic valve replacement.

BACKGROUND: Multi-detector computed tomography (MDCT) predicted orthogonal projection angles have been introduced to guide valve deployment during transcatheter aortic valve replacement (TAVR). Our aim was to investigate the accuracy of MDCT prediction methods versus actual angiographic deployment angles. METHODS: Retrospective analysis of 2 currently used MDCT methods: manual multiplanar reformations (MR) and the semiautomatic optimal angle graph (OAG). Paired analysis was used to compare the 2-dimensional distributions and means. RESULTS: We included 101 patients with a mean (±SD) age of 81 ±â€¯9 years. The MR and OAG methods were used in 46 and 55 patients, respectively. A ≥5% change from the predicted MDCT range in left anterior oblique/right anterior oblique (LAO/RAO) and the cranial/caudal (CRA/CAU) angle occurred in 42% and 58% of patients, respectively. The mean predicted versus actual deployment angles were significantly different (CRA/CAU: -2.6 ±â€¯11.5 vs. -7.6 ±â€¯10.7, p < 0.001; RAO/LAO 8.1 ±â€¯10.9 vs. 9.5 ±â€¯10.6, p = 0.048; respectively). The MR method resulted in a more accurate CRA/CAU angle (CRA/CAU: -4.6 ±â€¯11.1 vs. -6.5 ±â€¯11.8, p = 0.139; RAO/LAO 7.4 ±â€¯11.2 vs. 10.4 ±â€¯11.2, p = 0.008; respectively), whereas the use of the OAG resulted in a more accurate RAO/LAO angle (CRA/CAU: -0.9 ±â€¯10.8 vs. -9±11.2, p < 0.001; RAO/LAO 9.05 ±â€¯10.6 vs. 8.5 ±â€¯9.9, p = 0.458; respectively). For the entire cohort, the 2-dimensional distributions and means of the predicted versus the actual angles were significantly different from each other (p < 0.001). We repeated our analysis using both MDCT methods and demonstrated similar results with each method. CONCLUSIONS: Currently used MDCT methods for TAVR implantation angles are significantly modified before actual valve deployment. Thus, further refinement of these prediction methods is required.

Management and Outcome of Residual Aortic Regurgitation After Transcatheter Aortic Valve Implantation.

We aimed to evaluate the success rates of balloon valvuloplasty post-dilation (BVPD) and a second-valve deployment in reducing residual aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI) and its impact on outcome. Residual AR immediately post-TAVI in patients with aortic stenosis is a common condition that adversely affects outcome. Patients who underwent TAVI who had more-than-mild residual AR were managed either with medical therapy, re-intervention with BVPD, or a second valve. The clinical impact of these strategies was evaluated, and the anatomical features of patients with successful and unsuccessful intervention were compared. Among 572 patients with TAVI, 110 (19%) had significant residual AR after initial device deployment. Sixty patients were treated by BVPD (n = 49) or second-device deployment (n = 11), whereas 50 patients were treated medically. Successful reduction in residual AR to mild and below was achieved in 56% of the intervention group. Eccentric and calcified annuli were present in patients in whom residual AR remained despite re-intervention (p = 0.004). Interventions to reduce residual AR were independently associated with improved survival compared with conservative medical therapy (hazard ratio 0.45, 95% confidence interval 0.94 to 0.21, p = 0.03). BVPD or a second valve were safe and were not associated with increased rate of periprocedural complications. In conclusion, both BVPD and a second-valve deployment to reduce residual AR post-TAVI are effective and safe. The success rates are inversely correlated with the annulus eccentricity and calcification. These measures should be encouraged to reduce acute residual AR as they are associated with improved long-term survival.

A 28-year-old man with chest and joint pains.

CLINICAL INTRODUCTION: A 28-year-old man with extensive travel history to developing countries was hospitalised for intermittent sharp chest pains, worst when supine and with inspiration. Two weeks prior to presentation, he had suffered a flu-like illness with a sore throat, which was resolving. Physical examination was notable for mild fever and tachycardia with cervical lymphadenopathy and painful bilateral knee and wrist effusions. Cardiac auscultation was remarkable for a soft early-peaking systolic murmur over the aortic area with a decrescendo early diastolic murmur along the left sternal edge. There was mild leucocytosis, elevation of serum troponin and acute-phase reactants with an ECG showing sinus tachycardia. Echocardiographic windows were extremely limited but suggested the presence of pericardial effusion and aortic regurgitation. Cardiac MRI was performed (figure 1). Viral, microbiological and autoimmune testing was remarkable only for significant elevation of antistreptolysin-O titres (1450 IU rising to 1940 IU, normal <200 IU). Pericardiocentesis revealed an exudative effusion, which was negative by cytology and microbiological analysis, including for tuberculosis and fungi. QUESTION: The most appropriate next step is? Coronary angiographyEndomyocardial biopsyTreatment with colchicine for 3 monthsTreatment with corticosteroidsTreatment with high-dose salicylates and long-term penicillinFor the answer see page 808For the question see page 769.

Hemodynamic Consequences of Hypertrophic Cardiomyopathy with Midventricular Obstruction: Apical Aneurysm and Thrombus Formation.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) with midventricular hypertrophy is an uncommon phenotypic variant of the disease. Midventricular hypertrophy predisposes to intracavitary obstruction and downstream hemodynamic sequelae. CASE REPORT: We present a case of HCM with midventricular hypertrophy and obstruction diagnosed after a CT scan of the abdomen incidentally revealed a filling defect in the left ventricular apex. Transthoracic echocardiography demonstrated mid left ventricular hypertrophy and obstruction, as well as an aneurysmal apex containing a large thrombus. Cardiovascular MRI showed a spade-shaped left ventricle with midcavitary obliteration, an infarcted apex and regions of myocardial fibrosis. Due to the risk of embolization and a relative contraindication to anticoagulation, the patient underwent surgery including thrombectomy, septal myectomy and aneurysmal ligation. CONCLUSIONS: Hypertrophic cardiomyopathy with midventricular hypertrophy leads to cavity obstruction, increased apical wall tension, ischemia and ultimately fibrosis. Over time, patchy apical fibrosis can develop into a confluent scar resembling a transmural myocardial infarction in the left anterior descending coronary artery distribution. Aneurysmal remodeling of the left ventricular apex potentiates thrombus formation and risk of cardioembolism. For these reasons, hypertrophic cardiomyopathy with midventricular obstruction portends a particularly poor prognosis and should be recognized early in the disease process.

Radiation Dose Reduction during Radial Cardiac Catheterization: Evaluation of a Dedicated Radial Angiography Absorption Shielding Drape.

Objectives. Radiation scatter protection shield drapes have been designed with the goal of decreasing radiation dose to the operators during transfemoral catheterization. We sought to investigate the impact on operator radiation exposure of various shielding drapes specifically designed for the radial approach. Background. Radial access for cardiac catheterization has increased due to improved patient comfort and decreased bleeding complications. There are concerns for increased radiation exposure to patients and operators. Methods. Radiation doses to a simulated operator were measured with a RadCal Dosimeter in the cardiac catheterization laboratory. The mock patient was a 97.5 kg fission product phantom. Three lead-free drape designs were studied. The drapes were placed just proximal to the right wrist and extended medially to phantom's trunk. Simulated diagnostic coronary angiography included 6 minutes of fluoroscopy time and 32 seconds of cineangiography time at 4 standard angulated views (8 s each), both 15 frames/s. ANOVA with Bonferroni correction was used for statistical analysis. Results. All drape designs led to substantial reductions in operator radiation exposure compared to control (P < 0.0001). The greatest decrease in radiation exposure (72%) was with the L-shaped design. Conclusions. Dedicated radial shielding drapes decrease radiation exposure to the operator by up to 72% during simulated cardiac catheterization.