Clinical outcomes and safety of immune checkpoint inhibitors in patients with solid tumors and paraneoplastic syndromes.

BACKGROUND: Patients with paraneoplastic syndromes (PNS) are excluded from clinical trials involving immune checkpoint inhibitors (ICIs) due to safety concerns. Moreover, real-world data on efficacy and safety is scarce. METHODS: In this retrospective study, data were collected on patients with PNS and solid tumors receiving ICI between 2015 and 2022 at nine institutions. Patients were classified into: Cohort 1 (pre-existing PNS before ICI initiation), cohort 2 (PNS during ICI treatment), and cohort 3 (PNS after ICI discontinuation). Patients with metastatic non-small cell lung cancer (NSCLC) (mNSCLC) from cohort 1 were matched to patients who were PNS-free at each institution up to a 1:3 ratio for age, sex, type of ICI, use of concurrent chemotherapy, and number of lines of systemic therapy prior to ICI initiation. Kaplan-Meier method was used to assess overall survival (OS) and time-to-next treatment (TTNT). RESULTS: Among 109 patients with PNS treated with ICIs, median age at ICI initiation was 67 years (IQR: 58-74). The most represented cancer type was NSCLC (n=39, 36%). In cohort 1 (n=55), PNS exacerbations occurred in 16 (29%) patients with median time to exacerbation after ICI of 1.1 months (IQR: 0.7-3.3). Exacerbation or de novo PNS prompted temporary/permanent interruption of ICIs in 14 (13%) patients. For cohort 2 (n=16), median time between ICI initiation and de novo PNS was 1.2 months (IQR: 0.4-3.5). Treatment-related adverse events (trAEs) occurred in 43 (39%) patients. Grade ≥3 trAEs occurred in 18 (17%) patients. PNS-directed immunosuppressive therapy was required in 55 (50%) patients. We matched 18 patients with mNSCLC and PNS (cohort 1) to 40 without PNS, treated with ICIs. There was no significant difference in OS or TTNT between patients with mNSCLC with and without PNS, although a trend was seen towards worse outcomes in patients with PNS. TrAEs occurred in 6/18 (33%) and 14/40 (35%), respectively. Grade ≥3 trAEs occurred in 4 (22%) patients with PNS and 7 (18%) patients without PNS. CONCLUSIONS: Exacerbations of pre-existing PNS occurred in 29% of patients treated with ICIs and both exacerbations and de novo PNS occur early in the ICI course. TrAE from ICIs were similar between patients with and without PNS. Our data suggest that pre-existing PNS should not preclude consideration of ICI therapy although patients may not derive the same clinical benefit compared with patients without PNS.

A Case Series of Minimally Invasive Robotic-Assisted Resection of Cardiac Papillary Fibroelastoma: The Mayo Clinic Experience.

Papillary fibroelastomas (PFEs) are small, slowly growing benign cardiac tumors with clinically significant risk of embolization. Surgical excision is the definitive treatment of symptomatic PFE and is conventionally performed through a median sternotomy. In this study, we report a series of 12 patients, who underwent robotic-assisted PFE removal at the Mayo Clinic. PFE involved the mitral valve, left atrium, and tricuspid valve. No major complications occurred after the procedure, and most patients were discharged 4 days after the surgery. On follow-up, 1 patient demonstrated pericarditis.

Clinical Outcomes Among Immunotherapy-Treated Patients With Primary Cardiac Soft Tissue Sarcomas: A Multicenter Retrospective Study.

Background: Primary cardiac soft tissue sarcomas (CSTS) affect young adults, with dismal outcomes. Objectives: The aim of this study was to investigate the clinical outcomes of patients with CSTS receiving immune checkpoint inhibitors (ICIs). Methods: A retrospective, multi-institutional cohort study was conducted among patients with CSTS between 2015 and 2022. The patients were treated with ICI-based regimens. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Objective response rates were determined according to Response Evaluation Criteria in Solid Tumors version 1.1. Treatment-related adverse events were graded per the Common Terminology Criteria for Adverse Events version 5.0. Results: Among 24 patients with CSTS, 17 (70.8%) were White, and 13 (54.2%) were male. Eight patients (33.3%) had angiosarcoma. At the time of ICI treatment, 18 patients (75.0%) had metastatic CSTS, and 4 (16.7%) had locally advanced disease. ICIs were administered as the first-line therapy in 6 patients (25.0%) and as the second-line therapy or beyond in 18 patients (75.0%). For the 18 patients with available response data, objective response rate was 11.1% (n = 2 of 18). The median PFS and median OS in advanced and metastatic CSTS (n = 22) were 5.7 months (95% CI: 2.8-13.3 months) and 14.9 months (95% CI: 5.7-23.7 months), respectively. The median PFS and OS were significantly shorter in patients with cardiac angiosarcomas than in those with nonangiosarcoma CSTS: median PFS was 1.7 vs 11 months, respectively (P < 0.0001), and median OS was 3.0 vs 24.0 months, respectively (P = 0.008). Any grade treatment-related adverse events occurred exclusively in the 15 patients with nonangiosarcoma CSTS (n = 7 [46.7%]), of which 6 (40.0%) were grade ≥3. Conclusions: Although ICIs demonstrate modest activity in CSTS, durable benefit was observed in a subset of patients with nonangiosarcoma, albeit with higher toxicity.

Case Report: A myxoma with a far reach.

A 73-year-old woman presented to the emergency department with a syncopal episode and a history of dizzy spells. A transthoracic echocardiogram demonstrated a large left atrial mass extending into the right upper pulmonary veins. Subsequently, cardiac magnetic resonance imaging and coronary computed tomography angiography with three-dimensional reconstruction and printing of the heart and mass were performed, which demonstrated a high index of suspicion for an atypical left atrial myxoma. The mass was excised robotically, and the pathology report confirmed a diagnosis of myxoma.

Outcomes of transcatheter aortic valve replacement in patients with and without amyloidosis: A nationwide analysis from the United States.

BACKGROUND: Amyloidosis is a common comorbidity in elderly patients with aortic stenosis (AS) referred for transcatheter aortic valve replacement (TAVR). This study aims to assess the impact of amyloidosis on the clinical outcomes of TAVR. METHODS: This is a retrospective study of the National Inpatient Sample database that identified adult patients (≥18 years) with AS hospitalized for TAVR from 2016 through 2020 to compare outcomes in those with versus without amyloidosis. Our primary outcome was in-hospital mortality. Secondary outcomes included procedural complications, hospital length of stay (LOS), and total costs. TAVR trends in both cohorts were also evaluated. RESULTS: The total cohort included 304,710 patients with AS undergoing TAVR, of whom 410 had amyloidosis. Over the study period, TAVR trends increased significantly in patients with and without amyloidosis (both ptrend < 0.01). Patients with amyloidosis were more likely to be older males with atrial fibrillation/flutter, congestive heart failure, renal disease, and dementia compared to non-amyloidosis patients. After adjustment for baseline characteristics, patients with amyloidosis had similar odds of in-hospital mortality (adjusted odds ratio [aOR] 1.66, 95 % confidence interval [CI] 0.34-3.63), heart block (aOR 1.33, 95 % CI 0.84-2.10), permanent pacemaker insertion (aOR 0.67, 95 % CI 0.27-1.66), stroke (aOR 0.90, 95 % CI 0.32-3.13), acute kidney injury, major bleeding, blood transfusion, vascular complications, in addition to similar LOS (p = 0.21) and total costs (p = 0.18) compared to patients without amyloidosis. CONCLUSION: In patients with AS undergoing TAVR, comorbid amyloidosis is associated with similar in-hospital mortality and procedural complications compared to patients without amyloidosis.

Arrhythmic mitral valve prolapse and mitral annular disjunction: pathophysiology, risk stratification, and management.

Mitral valve prolapse (MVP) is the most frequent valve condition but remains a conundrum in many aspects, particularly in regard to the existence and frequency of an arrhythmic form (AMVP) and its link to sudden cardiac death. Furthermore, the presence, frequency, and significance of the anatomic functional feature called mitral annular disjunction (MAD) have remained widely disputed. Recent case series and cohorts have shattered the concept that MVP is most generally benign and have emphasized the various phenotypes associated with clinically significant ventricular arrhythmias, including AMVP. The definition, evaluation, follow-up, and management of AMVP represent the focus of the present review, strengthened by recent coherent studies defining an arrhythmic MVP phenotypic that would affect a small subset of patients with MVP at concentrated high risk. The role of MAD in this context is of particular importance, and this review highlights the characteristics of AMVP phenotypes and MAD, their clinical, multimodality imaging, and rhythmic evaluation. These seminal facts lead to proposing a risk stratification clinical pathway with consideration of medical, rhythmologic, and surgical management and have been objects of recent expert consensus statements and of proposals for new research directions.

Safety and efficacy of immune checkpoint inhibitors in advanced penile cancer: report from the Global Society of Rare Genitourinary Tumors.

BACKGROUND: Treatment options for penile squamous cell carcinoma are limited. We sought to investigate clinical outcomes and safety profiles of patients with penile squamous cell carcinoma receiving immune checkpoint inhibitors. METHODS: This retrospective study included patients with locally advanced or metastatic penile squamous cell carcinoma receiving immune checkpoint inhibitors between 2015 and 2022 across 24 centers in the United States, Europe, and Asia. Overall survival and progression-free survival were estimated using the Kaplan-Meier method. Objective response rates were determined per Response Evaluation Criteria in Solid Tumours 1.1 criteria. Treatment-related adverse events were graded per the Common Terminology Criteria for Adverse Events, version 5.0. Two-sided statistical tests were used for comparisons. RESULTS: Among 92 patients, 8 (8.7%) were Asian, 6 (6.5%) were Black, and 24 (29%) were Hispanic and/or Latinx. Median (interquartile range) age was 62 (53-70) years. In all, 83 (90%) had metastatic penile squamous cell carcinoma, and 74 (80%) had received at least second-line treatment. Most patients received pembrolizumab monotherapy (n = 26 [28%]), combination nivolumab-ipilimumab with or without multitargeted tyrosine kinase inhibitors (n = 23 [25%]), or nivolumab (n = 16 [17%]) or cemiplimab (n = 15 [16%]) monotherapies. Median overall and progression-free survival were 9.8 months (95% confidence interval = 7.7 to 12.8 months) and 3.2 months (95% confidence interval = 2.5 to 4.2 months), respectively. The objective response rate was 13% (n = 11/85) in the overall cohort and 35% (n = 7/20) in patients with lymph node-only metastases. Visceral metastases, Eastern Cooperative Oncology Group (ECOG) performance status of 1 or higher, and a higher neutrophil/lymphocyte ratio were associated with worse overall survival. Treatment-related adverse events occurred in 27 (29%) patients, and 9.8% (n = 9) of the events were grade 3 or higher. CONCLUSIONS: Immune checkpoint inhibitors are active in a subset of patients with penile squamous cell carcinoma. Future translational studies are warranted to identify patients more likely to derive clinical benefit from immune checkpoint inhibitors.

Case report: New is not always better: treatment of non-bacterial thrombotic endocarditis.

An elderly female with metastatic adenocarcinoma of the lung and atrial fibrillation presented with multiple embolic strokes while on anticoagulation with Apixaban. After further investigation, a TEE showed lesions of non-bacterial thrombotic endocarditis on the mitral valve. A decision to switch the patient to LMWH for anticoagulation was then made and a follow-up TEE showed resolution of the NBTE. In this abstract, we show that heparin should remain as the anticoagulation agent of choice in the setting of NBTE associated with malignancy.

Cardiac Masses Discovered by Echocardiogram; What to Do Next?

Cardiac tumors are rare conditions, typically diagnosed on autopsy, but with the advancement of imaging techniques they are now encountered more frequently in clinical practice. Echocardiography is often the initial method of investigation for cardiac masses and provides a quick and valuable springboard for their characterization. While some cardiac masses can be readily identified by echocardiography alone, several require incorporation of multiple data points to reach diagnostic certainty. Herein, we will provide an overview of the main clinical, diagnostic, and therapeutic characteristics of cardiac masses within the framework of their location.

Impact of atrial fibrillation on outcomes in asymptomatic severe aortic stenosis: a propensity-matched analysis.

Background: Atrial fibrillation (AF) portends poor prognosis in patients with aortic stenosis (AS). Objectives: This study aimed to study the association of AF vs. sinus rhythm (SR) with outcomes in asymptomatic severe AS during routine clinical practice. Methods: We identified 909 asymptomatic patients from 3,208 consecutive patients with aortic valve area ≤1.0 cm2 and left ventricular ejection fraction ≥50% at a tertiary academic center. Patients were grouped by rhythm at the time of transthoracic echocardiogram [SR: 820/909 (90%) and AF: 89/909 (10%)]. Propensity-matched analyses (2 SR:1 AF) matching 174 SR to 89 AF patients by age, sex, and clinical comorbidities were used to compare outcomes. Results: In the propensity-matched cohort, median age (82 ± 8 vs. 81 ± 9 years, p = 0.31), sex distribution (male 58% vs. 52%, p = 0.30), and Charlson comorbidity index (4.0 vs. 3.0, p = 0.26) were not different in AF vs. SR. Median follow-up duration was 2.6 (IQR: 1.0-4.4) years. The 1-year rate of aortic valve replacement (AVR) was not different (AF: 32% vs. SR: 37%, p = 0.31). All-cause mortality was higher in AF [hazard ratio (HR): 1.68 (1.13-2.50), p = 0.009]. Independent predictors of mortality were age [HR: 1.92 (1.40-2.62), p < 0.001], Charlson comorbidity index [1.09 (1.03-1.15), p = 0.002], aortic valve peak velocity [HR: 1.87 (1.20-2.94), p = 0.006], stroke volume index [HR: 0.75 (0.60-0.93), p = 0.01], moderate or more mitral regurgitation [HR: 2.97 (1.43-6.19), p = 0.004], right ventricular systolic dysfunction [HR: 2.39 (1.29-4.43), p = 0.006], and time-dependent AVR [HR: 0.36 (0.19-0.65), p = 0.0008]. There was no significant interaction of AVR and rhythm (p = 0.57). Conclusions: Lower forward flow, right ventricular systolic dysfunction, and mitral regurgitation identified increased risk of subsequent mortality in asymptomatic patients with AF and AS. Additional studies of risk stratification of asymptomatic AS in AF vs. SR are needed.

Outcomes of Transcatheter Aortic Valve Implantation in Nonagenarians and Octogenarians (Analysis from the National Inpatient Sample Database).

Risks among nonagenarian (age ≥90 years) and octogenarian (age 80 to 89 years) patients who underwent transcatheter aortic valve implantation (TAVI) compared with clinically similar septuagenarian (age 70 to 79 years) patients remain unclear. This study aimed to assess the outcomes of TAVI in nonagenarians and octogenarians compared with septuagenarians. We conducted a retrospective cohort study using the National Inpatient Sample database to identify patients aged ≥70 years hospitalized for TAVI from 2016 to 2020 and to compare outcomes in nonagenarians and octogenarians versus septuagenarians. The primary outcome was in-hospital mortality. Secondary outcomes included procedural complications, length of stay (LOS), and total costs. The trends in in-hospital outcomes were evaluated. Results were adjusted for demographic/clinical factors. The total cohort included 263,325 patients hospitalized for TAVI, of whom 11.9% were nonagenarians, 51.1% octogenarians, and 37.0% septuagenarians. After adjustment, nonagenarians and octogenarians had higher odds of in-hospital mortality (adjusted odds ratio 1.80, 95% confidence interval 1.34 to 2.41 for nonagenarians; adjusted odds ratio 1.65, 95% confidence interval 1.35 to 2.01 for octogenarians), heart block, permanent pacemaker insertion, stroke, major bleeding, blood transfusion, and palliative care consultation than septuagenarians (all p <0.01). LOS was longer and the total costs were higher for nonagenarians and octogenarians (both p <0.01). Over the study period, in-hospital mortality decreased in nonagenarians (ptrend = 0.04), and major bleeding, permanent pacemaker insertion, LOS, and costs decreased in all patients aged ≥70 years (ptrend <0.01). In conclusion, nonagenarians and octogenarians who underwent TAVI have higher rates of mortality and procedure-related complications than clinically similar septuagenarians. Further research is necessary to optimize outcomes in this frail population.

Safety and Activity of Immune Checkpoint Inhibitors in People Living With HIV and Cancer: A Real-World Report From the Cancer Therapy Using Checkpoint Inhibitors in People Living With HIV-International (CATCH-IT) Consortium.

PURPOSE: Compared with people living without HIV (PWOH), people living with HIV (PWH) and cancer have traditionally been excluded from immune checkpoint inhibitor (ICI) trials. Furthermore, there is a paucity of real-world data on the use of ICIs in PWH and cancer. METHODS: This retrospective study included PWH treated with anti-PD-1- or anti-PD-L1-based therapies for advanced cancers. Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Objective response rates (ORRs) were measured per RECIST 1.1 or other tumor-specific criteria, whenever feasible. Restricted mean survival time (RMST) was used to compare OS and PFS between matched PWH and PWOH with metastatic NSCLC (mNSCLC). RESULTS: Among 390 PWH, median age was 58 years, 85% (n = 331) were males, 36% (n = 138) were Black; 70% (n = 274) received anti-PD-1/anti-PD-L1 monotherapy. Most common cancers were NSCLC (28%, n = 111), hepatocellular carcinoma ([HCC]; 11%, n = 44), and head and neck squamous cell carcinoma (HNSCC; 10%, n = 39). Seventy percent (152/216) had CD4+ T cell counts ≥200 cells/µL, and 94% (179/190) had HIV viral load <400 copies/mL. Twenty percent (79/390) had any grade immune-related adverse events (irAEs) and 7.7% (30/390) had grade ≥3 irAEs. ORRs were 69% (nonmelanoma skin cancer), 31% (NSCLC), 16% (HCC), and 11% (HNSCC). In the matched mNSCLC cohort (61 PWH v 110 PWOH), 20% (12/61) PWH and 22% (24/110) PWOH had irAEs. Adjusted 42-month RMST difference was -0.06 months (95% CI, -5.49 to 5.37; P = .98) for PFS and 2.23 months (95% CI, -4.02 to 8.48; P = .48) for OS. CONCLUSION: Among PWH, ICIs demonstrated differential activity across cancer types with no excess toxicity. Safety and activity of ICIs were similar between matched cohorts of PWH and PWOH with mNSCLC.

Cardiotoxicities of Novel Therapies in Hematological Malignancies: Monoclonal Antibodies and Enzyme Inhibitors.

Monoclonal antibodies (mAB) selectively target leukemia surface antigens and work by either blocking cell surface receptors or triggering the target cell's destruction. Similarly, enzyme inhibitors bind to complex molecular platforms and induce downstream mechanisms that trigger cell death. These are used in a variety of hematologic malignancies. Yet, they also elicit severe immune-mediated reactions as biological agents that require careful monitoring. Cardiovascular effects include cardiomyopathy, ventricular dysfunction, cardiac arrest, and acute coronary syndrome. While there have been scattered reviews of mAB and enzyme inhibitors, a consolidated resource regarding their cardiovascular risk profile is lacking. We provide general recommendations for initial screening and serial monitoring based on the literature.

Racial and Ethnic Disparities in the Use and Outcomes of Transcatheter Mitral Valve Replacement: Analysis From the National Inpatient Sample Database.

Background Racial and ethnic disparities in outcomes exist following many cardiac procedures. Transcatheter mitral valve replacement (TMVR) has grown as an alternative to mitral valve surgery for patients at high surgical risk. The outcomes of TMVR by race and ethnicity are unknown. We aimed to evaluate racial and ethnic disparities in the outcomes of TMVR. Methods and Results We analyzed the National Inpatient Sample database from 2016 to 2020 to identify hospitalizations for TMVR. Racial and ethnic disparities in TMVR outcomes were determined using logistic regression models. Between 2016 and 2020, 5005 hospitalizations for TMVR were identified, composed of 3840 (76.7%) White race, 505 (10.1%) Black race, 315 (6.3%) Hispanic ethnicity, and 345 (6.9%) from other races (Asian, Pacific Islander, American Indian or Alaska Native, Other). Compared with other racial and ethnic groups, Black patients were significantly younger and more likely to be women (both P<0.01). There were no significant differences between White, Black, and Hispanic patients in in-hospital mortality (5.2% versus 5.0% versus <3.5%; P=0.89) and procedural complications, including heart block (P=0.91), permanent pacemaker (P=0.49), prosthetic valve dysfunction (P=0.45), stroke (P=0.37), acute kidney injury (P=0.32), major bleeding (P=0.23), and blood transfusion (P=0.92), even after adjustment for baseline characteristics. Adjusted vascular complications were higher in Black compared with White patients (P=0.03). Trend analysis revealed a significant increase in TMVR in all racial and ethnic groups from 2016 to 2020 (Ptrend<0.05). Conclusions Between 2016 and 2020, Black and Hispanic patients undergoing TMVR had similar in-hospital outcomes compared with White patients, except for higher vascular complications in Black patients. Further comparative studies of TMVR in clinically similar White patients and other racial and ethnic groups are warranted to confirm our findings.

Uric Acid Is Associated with Worsening of Diastolic Function and Adverse Outcomes in Patients with Coronary Slow Flow.

OBJECTIVE: The impact of uric acid on worsening of diastolic function and clinical outcomes in patients with coronary slow flow remains unclear. This study aims to investigate possible associations between serum uric acid, worsening of diastolic function, and major adverse cardiovascular events in coronary slow flow patients. METHODS: Blood samples were obtained prospectively from 537 patients who had been angiographically diagnosed with coronary slow flow. Of those, 425 patients underwent comprehensive cardiac function assessment both before and after maximal treadmill exertion by stress echocardiography. The association between serum uric acid and major adverse cardiovascular events was examined using Cox proportional hazards regression model. RESULTS: Among the 425 patients (mean age: 58 ± 11 years; 52.2% men), worsening of diastolic function occurred in 176 (41.4%) after exercise stress. Patients with worsening of diastolic function had elevated levels of serum uric acid compared to those without (5.7 [4.1, 6.7] vs 4.3 [3.6, 5.3] mg/dL, respectively; P <.001). Higher serum uric acid levels were also significantly associated with neutrophil counts and high-sensitive C-reactive protein in patients with worsening of diastolic function but not in those without. Multivariate regression analysis found serum uric acid to be an independent predictor of worsening of diastolic function (odds ratio = 1.87 [1.17-3.82], P =.023). Moreover, serum uric acid remained associated with major adverse cardiovascular events even after adjusting for echocardiographic and clinical variables (hazard ratio = 1.56 [1.03-2.89], P =.016). CONCLUSION: Serum uric acid is associated with worsening of diastolic function and may be mediated by inflammation. These findings indicate that uric acid is a risk factor for major adverse cardiovascular events in patients with coronary slow flow.

Sodium-Glucose Cotransporter-2 Inhibitors in Heart Failure With Mildly Reduced or Preserved Ejection Fraction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce the risk of heart failure (HF) hospitalizations and cardiovascular mortality among patients with HF and left ventricular ejection fraction (LVEF) ≤40%. There is emerging evidence of the benefits of SGLT2i in HF patients with a higher LVEF (>40%). We aimed to evaluate the benefits of SGLT2i in different subgroups of patients with HF and LVEF >40%. METHODS: We searched PubMed, EMBASE, clinicaltrials.gov, Cochrane, and Google Scholar for randomized controlled trials (RCTs) comparing outcomes of SGLT2i vs placebo in patients with HF and LVEF >40%. The hazard ratios (HRs) and 95% confidence intervals (CIs) in each study were used for the meta-analysis. The primary composite outcome (PCO) was HF hospitalization or cardiovascular mortality. Secondary outcomes included HF hospitalization, cardiovascular mortality, and all-cause mortality. RESULTS: Six RCTs with 15,989 patients were included (median follow-up = 27.3 months, 40.8% females). In patients with HF and LVEF >40%, SGLT2i were associated with significantly lower PCO compared to placebo (HR 0.80; 95% CI 0.74-0.86; P < 0.001). This was consistent across 10 of 13 subgroups examined, including LVEF. SGLT2i also reduced HF hospitalization but not cardiovascular or all-cause mortality. Patients <65 years old, from racial minorities, or from Asia receiving SGLT2i did not demonstrate a significant reduction in PCO. CONCLUSIONS: SGLT2i significantly reduce the combined risk of HF hospitalization or cardiovascular mortality among patients with HF and LVEF >40%. However, younger patients, racial minorities, and patients from Asia did not demonstrate such a reduction. Further research is necessary to identify the reasons for such disparities.

Underestimation of Aortic Stenosis Severity by Doppler Mean Gradient during Atrial Fibrillation: Insights from Aortic Valve Weight.

BACKGROUND: Doppler mean gradient (MG) can underestimate aortic stenosis (AS) severity when obtained during atrial fibrillation (AF) compared with sinus rhythm (SR). Aortic valve weight (AVW) is a flow-independent measure of AS severity. The objective of this study was to determine whether AVW or AVW/MG ratio was increased in AF versus SR in patients with AS. METHODS: Excised native aortic valves from 495 consecutive patients (median age, 77 years; interquartile range [IQR], 71-82 years; 40% women), with left ventricular ejection fractions ≥50% who underwent surgical aortic valve replacement for native valve severe AS (aortic valve area ≤ 1 cm2 or indexed aortic valve area ≤ 0.6 cm2/m2) were weighed. Excised AVW/MG ratios were compared in AF versus SR in patients with high-gradient AS (aortic peak velocity ≥ 4 m/sec or MG ≥ 40 mm Hg) and low-gradient AS (aortic peak velocity < 4 m/sec and MG < 40 mm Hg) in sex-specific analyses. RESULTS: AF was present in 51 patients (10%; 11 of 51 [22%] had low-gradient AS) and SR in 444 (90%; 23 of 444 [5%] had low-gradient AS). There was no difference in sex distribution between AF and SR. Aortic valve area was not different, but forward stroke volume index and transaortic valve flow rate were lower in AF (P ≤ .002 for all); MG was lower in AF versus SR (median, 46 mm Hg [IQR, 37-50 mm Hg] vs 50 mm Hg [IQR, 44-61 mm Hg]; P < .0001). Overall AVW was not different (median, 2,290 mg [IQR, 1,830-3,063 mg] vs 2,140 mg [IQR, 1,530-2,958 mg]; P = .31), but overall AVW/MG ratio was higher in AF (median, 55 [IQR, 41-67] vs 42 [IQR, 30-55]; P = .001). In sex- and MG-specific analyses, the AVW/MG ratio was higher in AF compared with SR in men with high-gradient AS (median, 58 [IQR, 41-75] vs 51 [IQR, 39-61]; P = .03), but the differences were not statistically significant between AF and SR in other groups. CONCLUSIONS: AVW was discordant to Doppler MG in AF compared with SR in men with high-gradient AS. Additional studies of the relationship of MG to other measures of AS severity, such as leaflet fibrosis, are needed.