Low vitamin D levels predict left atrial thrombus in nonvalvular atrial fibrillation

Background and aimsWe determined the association between left atrial (LA) thrombus occurrence and a non-classic risk marker, plasma levels of vitamin D, in atrial fibrillation (AF) patients on continuous non-vitamin K antagonist oral anticoagulant (NOAC) therapy for ≥4 weeks. Low levels of plasma 25-hydroxy vitamin D (25-OHD) are predictive of fatal stroke. Vitamin D has anticoagulant effects on the coagulation cascade, which are indirectly targeted by NOAC therapy. The impact of plasma levels of vitamin D on the rate of LA thrombus detected by transesophageal echocardiography (TEE) in AF patients is unknown.Methods and resultsWe enrolled 201 (133 female) AF patients who were using continuous NOAC therapy for ≥4 weeks. All patients underwent transthoracic and TEE examination. Serum concentrations of 25-OHD, C-reactive protein (CRP) levels, CHA₂DS₂-VASc scores and parameters, LA size, and left ventricle ejection fraction (LVEF) were examined before the TEE procedure. LA thrombus occurrence was independently associated with serum levels of 25-OHD (OR: 0.884; 95% CI: 0.839–0.932; P < 0.001), LA diameter (OR: 1.120; 95% CI: 1.038–1.209; P = 0.003), and LVEF(OR: 0.944; 95% CI: 0.896–0.995; P = 0.032). Dense spontaneous echo contrast (SEC) presence was also inversely associated with 25-OHD concentrations.ConclusionsLow 25-OHD levels, as a non-classic risk factor, were independently and significantly associated with dense SEC and LA thrombus occurrence in AF patients under NOAC therapy, as well as LA enlargement and decreased LVEF. Further large-scale studies are needed to explain the role of vitamin D deficiency, or efficacy of replacement, on LA thrombus occurrence.     

Impact of Pre-Existing and New-Onset Atrial Fibrillation on Outcomes After Transcatheter Aortic Valve Replacement

ObjectivesThis study sought to evaluate impact of new-onset and pre-existing atrial fibrillation (AF) on transcatheter aortic valve replacement (TAVR) long-term outcomes compared with patients without AF.BackgroundPre-existing and new-onset AF in patients undergoing TAVR are associated with poor outcomes.MethodsThe study identified 72,660 patients ≥65 years of age who underwent nonapical TAVR between 2014 and 2016 using Medicare inpatient claims. History of AF was defined by diagnoses on claims during the 3 years preceding the TAVR, and new-onset AF was defined as occurrence of AF during the TAVR admission or within 30 days after TAVR in a patient without prior history of AF. Outcomes included all-cause mortality, and readmission for bleeding, stroke, and heart failure (HF).ResultsOverall, 40.7% had pre-existing AF (n = 29,563) and 6.8% experienced new-onset AF (n = 2,948) after TAVR. Mean age was 81.3, 82.4, and 83.8 years in patients with no AF, pre-existing, and new-onset AF, respectively. Pre-existing AF patients had the highest burden of comorbidities. After follow-up of 73,732 person-years, mortality was higher with new-onset AF compared with pre-existing and no AF (29.7, 22.6, and 12.8 per 100 person-years, respectively; p < 0.001). After adjusting for patient characteristics and hospital TAVR volume, new-onset AF remained associated with higher mortality compared with no AF (adjusted hazard ratio: 2.068, 95% confidence interval [CI]: 1.92 to 2.20; p < 0.01) and pre-existing AF (adjusted hazard ratio: 1.35; 95% CI: 1.26 to 1.45; p < 0.01). In competing risk analysis, new-onset AF was associated with higher risk of bleeding (subdistribution hazard ratio [sHR]: 1.66; 95% CI: 1.48 to 1.86; p < 0.01), stroke (sHR: 1.92; 95% CI: 1.63 to 2.26; p < 0.01), and HF (sHR: 1.98; 95% CI: 1.81 to 2.16; p < 0.01) compared with pre-existing AF.ConclusionsIn patients undergoing TAVR, new-onset AF is associated with increased risk of mortality and bleeding, stroke, and HF hospitalizations compared with pre-existing AF or no AF.     

Prognostic Utility of Echocardiographic Atrial and Ventricular Strain Imaging in Patients With Cardiac Amyloidosis

ObjectivesThe prognostic value of echocardiographic atrial and ventricular strain imaging in patients with biopsy-proven cardiac amyloidosis was assessed.BackgroundAlthough left ventricular global longitudinal strain (GLS) is known to be predictive of outcome, the additive prognostic value of left (LA), right atrial (RA), and right ventricular (RV) strain is unclear.MethodsOne hundred thirty-six patients with cardiac amyloidosis and available follow-up data were studied by endomyocardial biopsy, noncardiac biopsy with supportive cardiac imaging, or autopsy confirmation. One hundred nine patients (80%) had light-chain, 23 (17%) had transthyretin, and 4 (3%) had amyloid A type cardiac amyloidosis. GLS, RV free wall strain, peak longitudinal LA strain, and peak longitudinal RA strain were measured from apical views. Clinical and routine echocardiographic data were compared. All-cause mortality was followed (median 5 years).ResultsStrain data were feasible for GLS in 127 (93%), LA strain in 119 (88%), RA strain in 117 (86%), and RV strain in 102 (75%). Strain values from all 4 chambers were significantly associated with survival. Hazard ratio (HR) and 95% confidence interval (CI) for low median strain values were as follows: GLS, HR: 2.3; 95% CI: 1.3 to 3.8 (p < 0.01); LA strain, HR: 7.5; 95% CI: 3.8 to 14.7 (p < 0.001); RA strain, HR: 3.5; 95% CI: 2.0 to 6.2 (p < 0.001); and RV free wall strain, HR: 2.8; 95% CI: 1.5 to 5.1 (p < 0.001). Peak longitudinal LA strain and RV strain remained independently associated with survival in multivariable analysis. Peak LA strain had the strongest association with survival (p < 0.001), and LA strain combined with GLS and RV free wall strain had the highest prognostic value (p < 0.001).ConclusionsStrain data from all 4 chambers had important prognostic associations with survival in patients with biopsy-confirmed cardiac amyloidosis. Peak longitudinal LA strain was particularly associated with prognosis. Atrial and ventricular strain have promise for clinical utility.     

Antithrombotic Therapy for Patients With Left Ventricular Mural Thrombus

BackgroundContemporary data are lacking regarding the prognosis and management of left ventricular thrombus (LVT).ObjectivesThe purpose of this study was to quantify the effect of anticoagulation therapy on LVT evolution using sequential imaging and to determine the impact of LVT regression on the incidence of thromboembolism, bleeding, and mortality.MethodsFrom January 2011 to January 2018, a comprehensive computerized search of LVT was conducted using 90,065 consecutive echocardiogram reports. Only patients with a confirmed LVT were included after imaging review by 2 independent experts. Major adverse cardiovascular events (MACE), which included death, stroke, myocardial infarction, or acute peripheral artery emboli, were determined as well as major bleeding events (BARC ≥3) and all-cause mortality rates.ResultsThere were 159 patients with a confirmed LVT. Patients were treated with vitamin K antagonists (48.4%), parenteral heparins (27.7%), and direct oral anticoagulants (22.6%). Antiplatelet therapy was used in 67.9% of the population. A reduction of the LVT area from baseline was observed in 121 patients (76.1%), and total LVT regression occurred in 99 patients (62.3%) within a median time of 103 days (interquartile range: 32 to 392 days). The independent correlates of LVT regression were a nonischemic cardiomyopathy (hazard ratio [HR]: 2.74; 95% confidence interval [CI]: 1.43 to 5.26; p = 0.002) and a smaller baseline thrombus area (HR: 0.66; 95% CI: 0.45 to 0.96; p = 0.031). The frequency of MACE was 37.1%; mortality 18.9%; stroke 13.3%; and major bleeding 13.2% during a median follow-up of 632 days (interquartile range: 187 to 1,126 days). MACE occurred in 35.4% and 40.0% of patients with total LVT regression and those with persistent LVT (p = 0.203). A reduced risk of mortality was observed among patients with total LVT regression (HR: 0.48; 95% CI: 0.23 to 0.98; p = 0.039), whereas an increased major bleeding risk was observed among patients with persistent LVT (9.1% vs. 12%; HR 0.34; 95% CI: 0.14 to 0.82; p = 0.011). A left ventricular ejection fraction ≥35% (HR: 0.46; 95% CI: 0.23 to 0.93; p = 0.029) and anticoagulation therapy >3 months (HR: 0.42; 95% CI: 0.20 to 0.88; p = 0.021) were independently associated with less MACE.ConclusionsThe presence of LVT was associated with a very high risk of MACE and mortality. Total LVT regression, obtained with different anticoagulant regimens, was associated with reduced mortality.     

Safety and Efficacy of Transcatheter Aortic Valve Replacement With Continuation of Vitamin K Antagonists or Direct Oral Anticoagulants

ObjectivesThis study investigated whether transcatheter aortic valve replacement (TAVR) with peri-procedural continuation of oral anticoagulation is equally safe and efficacious as TAVR with peri-procedural interruption of anticoagulation.BackgroundA significant proportion of patients undergoing TAVR have an indication for long-term oral anticoagulation. The optimal peri-procedural management of such patients is unknown.MethodsConsecutive patients on oral anticoagulation who underwent transfemoral TAVR at 5 European centers were enrolled. Oral anticoagulation was either stopped 2 to 4 days before TAVR or continued throughout the procedure. Primary safety outcome was major bleeding. Secondary efficacy endpoints included vascular complications, stroke, and mortality.ResultsOf 4,459 patients, 584 patients were treated with continuation of anticoagulation and 733 with interruption of anticoagulation. At 30 days, major or life-threatening bleedings occurred in 66 (11.3%) versus 105 (14.3%; odds ratio [OR]: 0.86; 95% confidence interval [CI]: 0.61 to 1.21; p = 0.39) and major vascular complications in 64 (11.0%) versus 90 (12.3%; OR: 0.89; CI: 0.62 to 1.27; p = 0.52) of patients with continuation and with interruption of anticoagulation, respectively. Transfusion of packed red blood cells was less often required in patients with continuation of anticoagulation (80 [13.7%] vs. 130 [17.7%]; OR: 0.59; 95% CI: 0.42 to 0.81; p = 0.001). Kaplan-Meier estimates of survival at 12 months were 85.3% in patients with continuation of anticoagulation and 84.0% in patients with interruption of anticoagulation (hazard ratio: 0.90; 95% CI: 0.73 to 1.12; p = 0.36).ConclusionsContinuation of oral anticoagulation throughout TAVR did not increase bleeding or vascular complication rates. Moreover, packed red blood cell transfusions were less often required in patients with continuation of oral anticoagulation.     

Oral Anticoagulation for Patients With Atrial Fibrillation on Long-Term Dialysis

BackgroundPatients on long-term dialysis are at increased risk of bleeding. Although oral anticoagulants (OACs) are recommended for atrial fibrillation (AF) to reduce the risk of stroke, randomized trials have excluded these populations. As such, the net clinical benefit of OACs among patients on dialysis is unknown.ObjectivesThis study aimed to investigate the efficacy and safety of OACs in patients with AF on long-term dialysis.MethodsMEDLINE and EMBASE were searched through June 10, 2019, for studies that investigated the efficacy and safety of different OAC strategies in patients with AF on long-term dialysis. The efficacy outcomes were ischemic stroke and/or systemic thromboembolism, all-cause mortality, and the safety outcome was major bleeding.ResultsThis study identified 16 eligible observational studies (N = 71,877) regarding patients on long-term dialysis who had AF. Only 2 of 16 studies investigated direct OACs. Outcomes for dabigatran and rivaroxaban were limited to major bleeding events. Compared with no anticoagulants, apixaban and warfarin were not associated with a significant decrease in stroke and/or systemic thromboembolism (apixaban 5 mg, hazard ratio [HR]: 0.59; 95% confidence interval [CI]: 0.30 to 1.17; apixaban 2.5 mg, HR: 1.00; 95% CI: 0.52 to 1.93; warfarin, HR: 0.91; 95% CI: 0.72 to 1.16). Apixaban 5 mg was associated with a significantly lower risk of mortality (vs. warfarin, HR: 0.65; 95% CI: 0.45 to 0.93; vs. apixaban 2.5 mg, HR: 0.62; 95% CI: 0.42 to 0.90; vs. no anticoagulant, HR: 0.61; 95% CI: 0.41 to 0.90). Warfarin was associated with a significantly higher risk of major bleeding than apixaban 5 min/2.5 mg and no anticoagulant (vs. apixaban 5 mg, HR: 1.41; 95% CI: 1.07 to 1.88; vs. apixaban 2.5 mg, HR: 1.40; 95% CI: 1.07 to 1.82; vs. no anticoagulant, HR: 1.31; 95% CI: 1.15 to 1.50). Dabigatran and rivaroxaban were also associated with significantly higher risk of major bleeding than apixaban and no anticoagulant.ConclusionsThis meta-analysis showed that OACs were not associated with a reduced risk of thromboembolism in patients with AF on long-term dialysis. Warfarin, dabigatran, and rivaroxaban were associated with significantly higher bleeding risk compared with apixaban and no anticoagulant. The benefit-to-risk ratio of OACs in patients with AF on long-term dialysis warrants validation in randomized clinical trials.     

Feasibility and Prognostic Value of Vasodilator Stress Perfusion CMR in Patients With Atrial Fibrillation

ObjectivesThe aim of this study was to assess the feasibility and prognostic value of vasodilator stress perfusion cardiovascular magnetic resonance (CMR) in patients with atrial fibrillation (AF).BackgroundBecause most studies have excluded arrhythmic patients, the prognostic value of stress perfusion CMR in patients with AF is unknown.MethodsBetween 2008 and 2018, consecutive patients with suspected or stable chronic coronary artery disease and AF referred for vasodilator stress perfusion CMR were included and followed for the occurrence of major adverse cardiovascular event(s) (MACE), defined as cardiovascular death or nonfatal myocardial infarction. The diagnosis of AF was defined by 12-lead electrocardiography before and after CMR. Univariate and multivariate Cox regressions were performed to determine the prognostic value of inducible ischemia or late gadolinium enhancement (LGE) by CMR.ResultsOf 639 patients (mean age 72 ± 9 years, 77% men), 602 (94%) completed the CMR protocol, and 538 (89%) completed follow-up (median 5.1 years); 80 had MACE. Using Kaplan-Meier analysis, the presence of ischemia (hazard ratio [HR]: 7.56; 95% confidence interval [CI]: 4.86 to 11.80) or LGE (HR: 2.41; 95% CI: 1.55 to 3.74) was associated with the occurrence of MACE (p < 0.001 for both). In a multivariate Cox regression including clinical and CMR indexes, the presence of ischemia (HR: 5.98; 95% CI: 3.68 to 9.73) or LGE (HR: 2.61; 95% CI: 1.89 to 3.60) was an independent predictor of MACE (p < 0.001 for both).ConclusionsIn patients with AF, stress perfusion CMR is feasible and has good discriminative prognostic value to predict the occurrence of MACE.     

Association of adipocytokines serum levels with left atrial thrombus formation in atrial fibrillation patients on oral anticoagulation (Alert) – A cross-sectional study

Background and aimsOral anticoagulation is effective for stroke prevention in atrial fibrillation (AF). However, strokes may still occur in high-risk individuals. We conducted a prospective trial to assess the association between adipocytokine serum levels and surrogate parameters for thromboembolic events.Methods and resultsIn this cross-sectional multicenter trial, we enrolled 189 patients with AF who were on oral anticoagulation. The primary endpoint was defined as either the presence of spontaneous echo contrast (SEC), a left atrial appendage (LAA), or a left atrial (LA) thrombus on transesophageal echocardiography. We investigated the association of adipocytokine serum levels with the combined endpoint using logistic regression analysis. Forty-eight individuals (25%) were assigned to group 1 (G1) due to the occurrence of at least one of the components of the combined endpoint (41 [21.7%] SEC, 3 [1.6%] LA thrombus, 13 [6.9%] LAA thrombus), whereas the remaining patients formed group 2 (G2). The BMI, logarithmized (log_e) leptin (G1: 2.0 ± 1.3 μg/ml, G2: 2.0 ± 1.1 μg/ml, p = 0.746) and visfatin serum levels (G1: 3.4 ± 0.3 ng/ml, G2: 3.4 ± 0.5 ng/ml, p = 0.900) did not significantly differ between the groups. Conversely, logarithmized adiponectin (G1: 3.3 ± 0.6 ng/ml, G2: 3.1 ± 0.7 ng/ml, p = 0.036) and resistin levels (G1: 1.8 ± 0.5 ng/ml, G2: 1.6 ± 0.5 ng/ml, p = 0.009) were higher in patients with the primary endpoint. Multivariate logistic regression analysis using a score that combined the individual adiponectin and resistin values in each patient corroborated this association.ConclusionsOur results suggest that adiponectin and resistin may act as potential biomarkers to identify individuals with AF who are at high thromboembolic risk.     

Left Atrial Appendage Closure Versus Direct Oral Anticoagulants in High-Risk Patients With Atrial Fibrillation

BackgroundPercutaneous left atrial appendage closure (LAAC) is noninferior to vitamin K antagonists (VKAs) for preventing atrial fibrillation (AF)–related stroke. However, direct oral anticoagulants (DOACs) have an improved safety profile over VKAs, and their effect on cardiovascular and neurological outcomes relative to LAAC is unknown.ObjectivesThis study sought to compare DOACs with LAAC in high-risk patients with AF.MethodsLeft Atrial Appendage Closure vs. Novel Anticoagulation Agents in Atrial Fibrillation (PRAGUE-17) was a multicenter, randomized, noninferiority trial comparing LAAC with DOACs. Patients were eligible to be enrolled if they had nonvalvular AF; were indicated for oral anticoagulation (OAC); and had a history of bleeding requiring intervention or hospitalization, a history of a cardioembolic event while taking an OAC, and/or a CHA₂DS₂-VASc of ≥3 and HAS-BLED of >2. Patients were randomized to receive LAAC or DOAC. The primary composite outcome was stroke, transient ischemic attack, systemic embolism, cardiovascular death, major or nonmajor clinically relevant bleeding, or procedure-/device-related complications. The primary analysis was by modified intention to treat.ResultsA high-risk patient cohort (CHA₂DS₂-VASc: 4.7 ± 1.5) was randomized to receive LAAC (n = 201) or DOAC (n = 201). LAAC was successful in 181 of 201 (90.0%) patients. In the DOAC group, apixaban was most frequently used (192 of 201; 95.5%). At a median 19.9 months of follow-up, the annual rates of the primary outcome were 10.99% with LAAC and 13.42% with DOAC (subdistribution hazard ratio [sHR]: 0.84; 95% confidence interval [CI]: 0.53 to 1.31; p = 0.44; p = 0.004 for noninferiority). There were no differences between groups for the components of the composite endpoint: all-stroke/TIA (sHR: 1.00; 95% CI: 0.40 to 2.51), clinically significant bleeding (sHR: 0.81; 95% CI: 0.44 to 1.52), and cardiovascular death (sHR: 0.75; 95% CI: 0.34 to 1.62). Major LAAC-related complications occurred in 9 (4.5%) patients.ConclusionsAmong patients at high risk for stroke and increased risk of bleeding, LAAC was noninferior to DOAC in preventing major AF-related cardiovascular, neurological, and bleeding events. (Left Atrial Appendage Closure vs. Novel Anticoagulation Agents in Atrial Fibrillation [PRAGUE-17]; NCT02426944)     

Left Atrial Late Gadolinium Enhancement is Associated With Incident Atrial Fibrillation as Detected by Continuous Monitoring With Implantable Loop Recorders

ObjectivesThe authors hypothesized that left atrial (LA) fibrosis was associated with incident atrial fibrillation (AF) as detected by continuous long-term monitoring in an at-risk population.BackgroundLA late gadolinium enhancement (LGE) measured with cardiac magnetic resonance is emerging as a marker of atrial fibrosis and has been associated with worse outcomes in AF ablation procedures; however, the prognostic value of LA LGE for incident AF remains unknown.MethodsCardiac magnetic resonance, including measurement of left ventricular and LA volumes and function, as well as left ventricular extracellular volume fraction and LA LGE, was acquired in 68 patients aged at least 70 years with risk factors for stroke. All included patients received an implantable loop recorder and were continuously monitored for previously unknown AF. Incident AF was adjudicated by senior cardiologists.ResultsPatients were monitored for AF with an implantable loop recorder during a median of 41 (interquartile range: 7) months. AF episodes lasting ≥6 min were detected in 32 patients (47%), and 16 patients (24%) experienced AF episodes lasting ≥5.5 h. In Cox regression analyses adjusted for sex, age, and comorbidities, we found that LA volumes and function and LA LGE were independently associated with incident AF. For LA LGE, the hazard ratios for time to AF episodes lasting ≥6 min and ≥5.5 h were 1.40 (95% CI: 1.03 to 1.89) per 10 cm² increase (p = 0.03) and 1.63 (95% CI: 1.11 to 2.40) per 10 cm² increase (p = 0.01), respectively. LA LGE was significantly associated with high burden of AF. The addition of LA LGE to a multivariable risk prediction model for incident AF significantly increased the predictive value.ConclusionsExtent of LA fibrosis measured by LA LGE was significantly associated with incident AF detected by implantable loop recorder. (Atrial Fibrillation Detected by Continuous ECG Monitoring [LOOP]; NCT02036450)     

Clinical Outcomes Associated With Left Atrial Appendage Occlusion Versus Direct Oral Anticoagulation in Atrial Fibrillation

ObjectivesThis study sought to investigate clinical outcomes associated with left atrial appendage occlusion (LAAO) versus direct oral anticoagulants (DOACs) in patients with high-risk atrial fibrillation (AF).BackgroundLAAO has been shown to be noninferior to warfarin for stroke prevention in AF. However, anticoagulation with DOACs is now preferred over warfarin as thromboprophylaxis in AF.MethodsPatients with AF enrolled in the Amulet Observational Registry (n = 1,088) who had successful LAAO with the Amplatzer Amulet device (n = 1,078) were compared with a propensity score–matched control cohort of incident AF patients (n = 1,184) treated by DOACs identified from Danish national patient registries. Propensity score matching was based on the covariates of the CHA₂DS₂-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism, vascular disease, age 65–74 years, sex category) and HAS-BLED (hypertension, abnormal renal or liver function, stroke, bleeding, labile international normalized ratio, elderly, drugs or alcohol) scores for predicting stroke and bleeding. The primary outcome was a composite of ischemic stroke, major bleeding (Bleeding Academic Research Consortium ≥3), or all-cause mortality, and follow-up was 2 years.ResultsAF patients treated with LAAO had a significantly lower risk of the primary composite outcome as compared with patients treated with DOACs (hazard ratio [HR]: 0.57; 95% confidence interval [CI]: 0.49 to 0.67). Total events and event rates per 100 patient-years were (LAAO vs. DOACs) 256 vs. 461 and 14.5 vs. 25.7, respectively. The risk of ischemic stroke was comparable between groups (HR: 1.11; 95% CI: 0.71 to 1.75), while risk of major bleeding (HR: 0.62; 95% CI: 0.49 to 0.79) and all-cause mortality (HR: 0.53; 95% CI: 0.43 to 0.64) were significantly lower in patients treated with LAAO.ConclusionsAmong high-risk AF patients, LAAO in comparison with DOACs may have similar stroke prevention efficacy but lower risk of major bleeding and mortality.     

Mitral Annular Dynamics in AF Versus Sinus Rhythm: Novel Insights Into the Mechanism of AFMR

ObjectivesThis study aimed to investigate mitral annular dynamics in atrial fibrillation (AF) and after sinus rhythm restoration, and to assess the relationship between annular dynamics and mitral regurgitation (MR).BackgroundAF can be associated with MR that improves after sinus rhythm restoration. Mechanisms underlying this atrial functional MR (AFMR) are ill-understood and generally attributed to left atrial remodeling.MethodsFifty-three patients with persistent AF and normal left ventricular ejection fraction were prospectively examined by means of 3-dimensional transesophageal echocardiography before, immediately after, and 6 weeks after electric cardioversion to sinus rhythm. Annular motion was assessed during AF and in sinus rhythm with the use of 3-dimensional analysis software, and the relationship with MR severity was explored.ResultsDuring AF and immediately after sinus rhythm restoration, the mitral annulus behaved relatively adynamically, with an overall change in annular area of 10.3% (95% CI: 8.7%-11.8%) and 12.2% (95% CI: 10.6%-13.8%), respectively. At follow-up, a significant increase in annular dynamics (19.0%; 95% CI: 17.4%-20.6%; P < 0.001) was observed, owing predominantly to an increase in presystolic contraction (P < 0.001). The effective regurgitant orifice area decreased from 0.15 cm² (0.10-0.23 cm²) during AF to 0.09 cm² (0.05-0.12 cm²) at follow-up (P < 0.001) in the total cohort, and from 0.27 (0.23-0.33) to 0.16 (0.12-0.29) in the subgroup with effective regurgitant orifice area (EROA) ≥0.20 cm². The change in presystolic annular motion was the only independent determinant of the decrease in MR severity (P = 0.027), by optimizing annular-leaflet imbalance. Patients with more pronounced blunting of presystolic dynamics had a higher EROA (P < 0.001), because of a lower total-to-closed leaflet area ratio (P < 0.001) at each point in time. This ratio was the strongest independent determinant of AFMR severity (adjusted P = 0.003).ConclusionsMitral annular dynamics are impaired in AF, with blunted presystolic narrowing that contributes to AFMR. Sinus rhythm restoration allows gradual recovery of presystolic annular dynamics. Improved annular dynamics decrease AFMR severity by optimizing annular-leaflet imbalance, regardless of LA remodeling.     

Myocarditis in Relation to Angiographic Findings in Patients With Provisional Diagnoses of MINOCA

ObjectivesThe aim of this study was to determine the prevalence of myocarditis among patients presenting with myocardial infarction with nonobstructive coronary arteries (MINOCA) in relation to the angiographic severity of nonobstructive coronary artery disease (CAD).BackgroundMINOCA represents about 6% of all cases of acute myocardial infarction. Myocarditis is a diagnosis that may be identified by cardiac magnetic resonance (CMR) imaging in patients with a provisional diagnosis of MINOCA.MethodsA systematic review was performed to identify studies reporting the results of CMR findings in MINOCA patients with nonobstructive CAD or normal coronary arteries. Study-level and individual patient data meta-analyses were performed using fixed- and random-effects methods.ResultsTwenty-seven papers were included, with 2,921 patients with MINOCA; CMR findings were reported in 2,866 (98.1%). Myocarditis prevalence was 34.5% (95% confidence interval [CI]: 27.2% to 42.2%) overall and was numerically higher in studies that defined MINOCA as myocardial infarction with angiographically normal coronary arteries compared with a definition that permitted nonobstructive CAD (45.9% vs. 32.3%; p = 0.16). In a meta-analysis of individual patient data from 9 of the 27 studies, the pooled prevalence of CMR-confirmed myocarditis was greater in patients with angiographically normal coronary arteries than in those with nonobstructive CAD (51% [95% CI: 47% to 56%] vs. 23% [95% CI: 18% to 27%]; p < 0.001). Men and younger patients with MINOCA were more likely to have myocarditis. Angiographically normal coronary arteries were associated with increased odds of myocarditis after adjustment for age and sex (adjusted odds ratio: 2.30; 95% CI: 1.12 to 4.71; p = 0.023).ConclusionsPatients with a provisional diagnosis of MINOCA are more likely to have CMR findings consistent with myocarditis if they have angiographically normal coronary arteries.     

3-Year Outcomes of Transcatheter Mitral Valve Repair in Patients With Heart Failure

BackgroundIn the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial, transcatheter mitral valve repair (TMVr) resulted in fewer heart failure hospitalizations (HFHs) and lower mortality at 24 months in patients with heart failure (HF) with mitral regurgitation (MR) secondary to left ventricular dysfunction compared with guideline-directed medical therapy (GDMT) alone.ObjectivesThis study determined if these benefits persisted to 36 months and if control subjects who were allowed to cross over at 24 months derived similar benefit.MethodsThis study randomized 614 patients with HF with moderate-to-severe or severe secondary MR, who remained symptomatic despite maximally tolerated GDMT, to TMVr plus GDMT versus GDMT alone. The primary effectiveness endpoint was all HFHs through 24-month follow-up. Patients have now been followed for 36 months.ResultsThe annualized rates of HFHs per patient-year were 35.5% with TMVr and 68.8% with GDMT alone (hazard ratio [HR]: 0.49; 95% confidence interval [CI]: 0.37 to 0.63; p < 0.001; number needed to treat (NNT) = 3.0; 95% CI: 2.4 to 4.0). Mortality occurred in 42.8% of the device group versus 55.5% of control group (HR: 0.67; 95% CI: 0.52 to 0.85; p = 0.001; NNT = 7.9; 95% CI: 4.6 to 26.1). Patients who underwent TMVr also had sustained 3-year improvements in MR severity, quality-of-life measures, and functional capacity. Among 58 patients assigned to GDMT alone who crossed over and were treated with TMVr, the subsequent composite rate of mortality or HFH was reduced compared with those who continued on GDMT alone (adjusted HR: 0.43; 95% CI: 0.24 to 0.78; p = 0.006).ConclusionsAmong patients with HF and moderate-to-severe or severe secondary MR who remained symptomatic despite GDMT, TMVr was safe, provided a durable reduction in MR, reduced the rate of HFH, and improved survival, quality of life, and functional capacity compared with GDMT alone through 36 months. Surviving patients who crossed over to device treatment had a prognosis comparable to those originally assigned to transcatheter therapy. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation [COAPT]; NCT01626079)     

Cardiac Radiation Dose,Cardiac Disease,and Mortality in Patients With Lung Cancer

BackgroundRadiotherapy-associated cardiac toxicity studies in patients with locally advanced non–small cell lung cancer (NSCLC) have been limited by small sample size and nonvalidated cardiac endpoints.ObjectivesThe purpose of this analysis was to ascertain whether cardiac radiation dose is a predictor of major adverse cardiac events (MACE) and all-cause mortality (ACM).MethodsThis retrospective analysis included 748 consecutive locally advanced NSCLC patients treated with thoracic radiotherapy. Fine and Gray and Cox regressions were used to identify predictors for MACE and ACM, adjusting for lung cancer and cardiovascular prognostic factors, including pre-existing coronary heart disease (CHD).ResultsAfter a median follow-up of 20.4 months, 77 patients developed ≥1 MACE (2-year cumulative incidence, 5.8%; 95% confidence interval [CI]: 4.3% to 7.7%), and 533 died. Mean radiation dose delivered to the heart (mean heart dose) was associated with a significantly increased risk of MACE (adjusted hazard ratio [HR]: 1.05/Gy; 95% CI: 1.02 to 1.08/Gy; p < 0.001) and ACM (adjusted HR: 1.02/Gy; 95% CI: 1.00 to 1.03/Gy; p = 0.007). Mean heart dose (≥10 Gy vs. <10 Gy) was associated with a significantly increased risk of ACM in CHD-negative patients (178 vs. 118 deaths; HR: 1.34; 95% CI: 1.06 to 1.69; p = 0.014) with 2-year estimates of 52.2% (95% CI: 46.1% to 58.5%) versus 40.0% (95% CI: 33.5% to 47.4%); but not among CHD-positive patients (112 vs. 82 deaths; HR: 0.94; 95% CI: 0.70 to 1.25; p = 0.66) with 2-year estimates of 54.6% (95% CI: 46.8% to 62.7%) versus 50.8% (95% CI: 41.5% to 60.9%), respectively (p for interaction = 0.028).ConclusionsDespite the competing risk of cancer-specific death in locally advanced NSCLC patients, cardiac radiation dose exposure is a modifiable cardiac risk factor for MACE and ACM, supporting the need for early recognition and treatment of cardiovascular events and more stringent avoidance of high cardiac radiotherapy dose.     

Direct Oral Anticoagulants in Patients With Atrial Fibrillation and Liver Disease

BackgroundAdvanced liver disease is known to increase the risk for bleeding and affects the hepatic clearance and metabolism of drugs. Subjects with active liver disease were excluded from pivotal clinical trials of direct oral anticoagulants (DOACs), so the evidence regarding the efficacy and safety of DOACs in patients with liver disease is lacking.ObjectivesThe aim of this study was to compare DOACs with warfarin in patients with nonvalvular atrial fibrillation and liver disease.MethodsUsing the Korean National Health Insurance Service database, subjects with atrial fibrillation and active liver disease treated with oral anticoagulation were included (12,778 with warfarin and 24,575 with DOACs), and analyzed ischemic stroke, intracranial hemorrhage, gastrointestinal bleeding, major bleeding, all-cause death, and the composite outcome. Propensity score weighting was used to balance covariates between the 2 groups.ResultsDOACs were associated with lower risks for ischemic stroke (hazard ratio [HR]: 0.548; 95% confidence interval [CI]: 0.485 to 0.618), intracranial hemorrhage (HR: 0.479; 95% CI 0.394 to 0.581), gastrointestinal bleeding (HR: 0.819; 95% CI: 0.619 to 0.949), major bleeding (HR: 0.650; 95% CI: 0.575 to 0.736), all-cause death (HR: 0.698; 95% CI: 0.636 to 0.765), and the composite outcome (HR: 0.610; 95% CI: 0.567 to 0.656) than warfarin. Among the total study population, 13% of patients (n = 4,942) were identified as having significant active liver disease. A consistent benefit was observed in patients with significant active liver disease (HR for the composite outcome: 0.691; 95% CI: 0.577 to 0.827).ConclusionsIn this large Asian population with atrial fibrillation and liver disease, DOACs showed better effectiveness and safety than warfarin, which was consistent in those with significant active liver disease.     

Prognostic Value of RCA Pericoronary Adipose Tissue CT-Attenuation Beyond High-Risk Plaques,Plaque Volume,and Ischemia

ObjectivesThis study was designed to assess the prognostic value of pericoronary adipose tissue computed tomography attenuation (PCATa) beyond quantitative coronary computed tomography angiography (CCTA)–derived plaque volume and positron emission tomography (PET) determined ischemia.BackgroundInflammation plays a crucial role in atherosclerosis. PCATa has been shown to assess coronary-specific inflammation and is of prognostic value in patients with suspected coronary artery disease (CAD).MethodsA total of 539 patients who underwent CCTA and [¹⁵O]H₂O PET perfusion imaging because of suspected CAD were included. Imaging assessment included coronary artery calcium score (CACS), presence of obstructive CAD (≥50% stenosis) and high-risk plaques (HRPs), total plaque volume (TPV), calcified/noncalcified plaque volume (CPV/NCPV), PCATa, and myocardial ischemia. The endpoint was a composite of death and nonfatal myocardial infarction. Prognostic thresholds were determined for quantitative CCTA variables.ResultsDuring a median follow-up of 5.0 (interquartile range: 4.7 to 5.0) years, 33 events occurred. CACS >59 Agatston units, obstructive CAD, HRPs, TPV >220 mm³, CPV >110 mm³, NCPV >85 mm³, and myocardial ischemia were associated with shorter time to the endpoint with unadjusted hazard ratios (HRs) of 4.17 (95% confidence interval [CI]: 1.80 to 9.64), 4.88 (95% CI: 1.88 to 12.65), 3.41 (95% CI: 1.72 to 6.75), 7.91 (95% CI: 3.05 to 20.49), 5.82 (95% CI: 2.40 to 14.10), 8.07 (95% CI: 3.33 to 19.55), and 4.25 (95% CI: 1.84 to 9.78), respectively (p < 0.05 for all). Right coronary artery (RCA) PCATa above scanner specific thresholds was associated with worse prognosis (unadjusted HR: 2.84; 95% CI: 1.44 to 5.63; p = 0.003), whereas left anterior descending artery and circumflex artery PCATa were not related to outcome. RCA PCATa above scanner specific thresholds retained is prognostic value adjusted for imaging variables and clinical characteristics associated with the endpoint (adjusted HR: 2.45; 95% CI: 1.23 to 4.93; p = 0.011).ConclusionsParameters associated with atherosclerotic burden and ischemia were more strongly associated with outcome than RCA PCATa. Nonetheless, RCA PCATa was of prognostic value beyond clinical characteristics, CACS, obstructive CAD, HRPs, TPV, CPV, NCPV, and ischemia.     

Incidence and Predictors of Atrial Fibrillation in Cardiac Sarcoidosis: A Multimodality Imaging Study

BackgroundIn cardiac sarcoidosis (CS), the risk and predictors of new-onset atrial fibrillation (AF) are poorly known.ObjectivesThe authors evaluated the incidence and characteristics of AF in newly diagnosed CS.MethodsThe authors studied 118 patients (78 women, mean age 50 years) with AF-naive CS having undergone cardiac ¹⁸F-fluorodexoyglucose positron emission tomography (¹⁸F-FDG PET) at the time of diagnosis. Details of patient characteristics and medical or device therapy were collected from hospital charts. The PET scans were re-analyzed for presence of atrial and ventricular inflammation, and coincident cardiac magnetic resonance (CMR) studies and single-photon emission computed tomography (SPECT) perfusions were analyzed for cardiac structure and function, including the presence and extent of myocardial scarring. Detection of AF was based on interrogation of intracardiac devices and on ambulatory or 12-lead electrocardiograms.ResultsAltogether 34 patients (29%) suffered paroxysms of AF during follow-up (median, 3 years) with persistent AF developing in 7 patients and permanent AF in 4. The estimated 5-year incidence of AF was 55% (95% CI: 34%-72%) in the 39 patients with atrial ¹⁸F-FDG uptake at the time of diagnosis vs 18% (95% CI: 10%-28%) in the 79 patients without atrial uptake (P < 0.001). In cause-specific Cox regression analysis, atrial uptake was an independent predictor of AF (P < 0.001) with HR of 6.01 (95% CI: 2.64-13.66). Other independent predictors were an increased left atrial maximum volume (P < 0.01) and history of sleep apnea (P < 0.01). Ventricular involvement by PET, SPECT, or CMR was nonpredictive. Symptoms of AF prompted electrical cardioversion in 12 patients (35%). Three of the 34 patients (9%) experiencing AF suffered a stroke versus none of those remaining free of AF.ConclusionsIn newly diagnosed CS, future AF is relatively common and associated with atrial inflammation and enlargement on multimodality cardiac imaging.     

Long-Term Prognostic Value of Stress CMR in Patients With Heart Failure and Preserved Ejection Fraction

ObjectivesThe objectives of this study were to investigate the long-term prognostic value of inducible myocardial ischemia assessed by vasodilator stress cardiovascular magnetic resonance (CMR) in patients with HFpEF.BackgroundSome studies suggest that ischemia could play a key role in HF in patients with preserved ejection fraction (HFpEF).MethodsBetween 2008 and 2019, consecutive patients prospectively referred for stress CMR with HFpEF as defined by current guidelines, without known coronary artery disease (CAD), were followed for the occurrence of major adverse cardiovascular events (MACE), as defined by cardiovascular mortality or nonfatal myocardial infarction (MI). Secondary composite outcomes included cardiovascular mortality or hospitalization for acute HF. Cox regression analysis was performed to determine the prognostic value of inducible ischemia or late gadolinium enhancement (LGE) by CMR.ResultsAmong the 1,203 patients with HFpEF (73 ± 13 years of age; 29% males) who underwent stress CMR and completed follow-up (6.9 years interquartile range [IQR]: 6.7 to 7.7 years]), 108 experienced a MACE (9%). Kaplan-Meier analysis showed inducible ischemia and LGE were significantly associated with MACE (HR: 6.63; 95% confidence interval [CI]: 4.54 to 9.69; and HR: 2.56; 95% CI: 1.60 to 4.09, respectively; both p < 0.001) and secondary outcomes (HR: 8.40; 95% CI: 6.31 to 11.20; p < 0.001; and HR: 1.87; 95% CI: 1.27 to 2.76, respectively; p = 0.002). In multivariate analysis, inducible ischemia and LGE were independent predictors of MACE (HR: 6.10; 95% CI: 4.14 to 9.00; p < 0.001 and HR: 1.62; 95% CI: 1.06 to 2.49; p = 0.039; respectively).ConclusionsStress CMR-inducible myocardial ischemia and LGE have accurate discriminative long-term prognostic value in HFpEF patients without known CAD to predict the occurrence of MACE.