Magnetic Resonance Imaging in Pediatric Myocarditis: Trends and Associations With Cost and Outcome

BackgroundCardiac magnetic resonance (CMR) provides tissue characterization and structural and functional data. CMR has high sensitivity and specificity for myocarditis in adults and children. The relationship between pediatric CMR use, cost, and clinical outcome has not been studied.ObjectivesThis work aims to describe temporal trends in CMR imaging for pediatric myocarditis and examine associations between CMR use, hospital cost, and outcomes.MethodsA retrospective cohort study of all inpatients <21 years of age with a diagnosis of myocarditis reported to the Pediatric Health Information System (2004-2019) was performed. Trends in CMR use were examined. A propensity-matched subcohort using center and patient level variables was used to assess whether outcomes differed by CMR use.ResultsA total of 4,195 children with myocarditis from 47 hospitals were identified. The median age was 11.5 years (IQR: 1.5-16.0 years) and 2,617 (62%) were male. CMR was used in 23% and mortality occurred in 6%. CMR use during hospitalization increased from 2% in 2004 to 37% in 2019 (odds ratio [OR]: 1.19 [95% CI: 1.17-1.21]). After propensity score matching, CMR use was associated with higher median cost (+$5,340 [95% CI: +$1,739 to +$9,936]) and similar median length of stay (0 days [95% CI: ?1 to +1 days]). Using quantile regression, CMR was associated with lower 90th percentile cost (?$77,200 [95% CI: ?$127,373 to ?$31,339]). More children receiving CMR were discharged alive in the first 30 days after admission (OR: 1.89 days [95% CI: 1.28-2.29]). Within the propensity matched cohort, <10 of 790 CMR recipients died compared to 42 of 790 in the non-CMR group.ConclusionsCMR use in children with myocarditis has increased over the past 15 years. CMR use is associated with higher cost of hospitalization and similar length of stay for most children but lower cost among the sickest children. CMR use in specific patients may improve clinical outcomes at a lower cost.     

Incident Clinical and Mortality Associations of Myocardial Native T1 in the UK Biobank

BackgroundCardiac magnetic resonance native T1-mapping provides noninvasive, quantitative, and contrast-free myocardial characterization. However, its predictive value in population cohorts has not been studied.ObjectivesThe associations of native T1 with incident events were evaluated in 42,308 UK Biobank participants over 3.17 ± 1.53 years of prospective follow-up.MethodsNative T1-mapping was performed in 1 midventricular short-axis slice using the Shortened Modified Look-Locker Inversion recovery technique (WIP780B) in 1.5-T scanners (Siemens Healthcare). Global myocardial T1 was calculated using an automated tool. Associations of T1 with: 1) prevalent risk factors (eg, diabetes, hypertension, and high cholesterol); 2) prevalent and incident diseases (eg, any cardiovascular disease [CVD], any brain disease, valvular heart disease, heart failure, nonischemic cardiomyopathies, cardiac arrhythmias, atrial fibrillation [AF], myocardial infarction, ischemic heart disease [IHD], and stroke); and 3) mortality (eg, all-cause, CVD, and IHD) were examined. Results are reported as odds ratios (ORs) or HRs per SD increment of T1 value with 95% CIs and corrected P values, from logistic and Cox proportional hazards regression models.ResultsHigher myocardial T1 was associated with greater odds of a range of prevalent conditions (eg, any CVD, brain disease, heart failure, nonischemic cardiomyopathies, AF, stroke, and diabetes). The strongest relationships were with heart failure (OR: 1.41 [95% CI: 1.26-1.57]; P = 1.60 × 10^-9) and nonischemic cardiomyopathies (OR: 1.40 [95% CI: 1.16-1.66]; P = 2.42 × 10^-4). Native T1 was positively associated with incident AF (HR: 1.25 [95% CI: 1.10-1.43]; P = 9.19 × 10^-4), incident heart failure (HR: 1.47 [95% CI: 1.31-1.65]; P = 4.79 × 10^-11), all-cause mortality (HR: 1.24 [95% CI: 1.12-1.36]; P = 1.51 × 10^-5), CVD mortality (HR: 1.40 [95% CI: 1.14-1.73]; P = 0.0014), and IHD mortality (HR: 1.36 [95% CI: 1.03-1.80]; P = 0.0310).ConclusionsThis large population study demonstrates the utility of myocardial native T1-mapping for disease discrimination and outcome prediction.     

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.     

Diagnostic Accuracy of Cardiovascular Magnetic Resonance for Cardiac Transplant Rejection: A Meta-Analysis

ObjectivesThe aim of this meta-analysis was to assess the diagnostic performance of various CMR imaging parameters for evaluating acute cardiac transplant rejection.BackgroundEndomyocardial biopsy is the current gold standard for detection of acute cardiac transplant rejection. Cardiac magnetic resonance (CMR) is uniquely capable of myocardial tissue characterization and may be useful as a noninvasive alternative for the diagnosis of graft rejection.MethodsPubMed and Web of Science were searched for relevant publications reporting on the use of CMR myocardial tissue characterization for detection of acute cardiac transplant rejection with endomyocardial biopsy as the reference standard. Pooled sensitivity, specificity, and hierarchical modeling–based summary receiver-operating characteristic curves were calculated.ResultsOf 478 papers, 10 studies comprising 564 patients were included. The sensitivity and specificity for the detection of acute cardiac transplant rejection were 84.6 (95% CI: 65.6-94.0) and 70.1 (95% CI: 54.2-82.2) for T1, 86.5 (95% CI: 72.1-94.1) and 85.9 (95% CI: 65.2-94.6) for T2, 91.3 (95% CI: 63.9-98.4) and 67.6 (95% CI: 56.1-77.4) for extracellular volume fraction (ECV), and 50.1 (95% CI: 31.2-68.9) and 60.2 (95% CI: 36.7-79.7) for late gadolinium enhancement (LGE). The areas under the hierarchical modeling–based summary receiver-operating characteristic curve were 0.84 (95% CI: 0.81-0.87) for T1, 0.92 (95% CI: 0.89-94) for T2, 0.78 (95% CI: 0.74-0.81) for ECV, and 0.56 (95% CI: 0.51-0.60) for LGE. T2 values demonstrated the highest diagnostic accuracy, followed by native T1, ECV, and LGE (all P values <0.001 for T1, ECV, and LGE vs T2).ConclusionsT2 mapping demonstrated higher diagnostic accuracy than other CMR techniques. Native T1 and ECV provide high diagnostic use but lower diagnostic accuracy compared with T2, which was related primarily to lower specificity. LGE showed poor diagnostic performance for detection of rejection.     

Acute Cardiac Events During COVID-19-Associated Hospitalizations

BackgroundCOVID-19 is associated with cardiac complications.ObjectivesThe purpose of this study was to estimate the prevalence, risk factors, and outcomes associated with acute cardiac events during COVID-19-associated hospitalizations among adults.MethodsDuring January 2021 to November 2021, medical chart abstraction was conducted on a probability sample of adults hospitalized with laboratory-confirmed SARS-CoV-2 infection identified from 99 U.S. counties in 14 U.S. states in the COVID-19-Associated Hospitalization Surveillance Network. We calculated the prevalence of acute cardiac events (identified by International Classification of Diseases-10th Revision-Clinical Modification codes) by history of underlying cardiac disease and examined associated risk factors and disease outcomes.ResultsAmong 8,460 adults, 11.4% (95% CI: 10.1%-12.9%) experienced an acute cardiac event during a COVID-19-associated hospitalization. Prevalence was higher among adults who had underlying cardiac disease (23.4%; 95% CI: 20.7%-26.3%) compared with those who did not (6.2%; 95% CI: 5.1%-7.6%). Acute ischemic heart disease (5.5%; 95% CI: 4.5%-6.5%) and acute heart failure (5.4%; 95% CI: 4.4%-6.6%) were the most prevalent events; 0.3% (95% CI: 0.1%-0.5%) experienced acute myocarditis or pericarditis. Risk factors varied by underlying cardiac disease status. Patients with ≥1 acute cardiac event had greater risk of intensive care unit admission (adjusted risk ratio: 1.9; 95% CI: 1.8-2.1) and in-hospital death (adjusted risk ratio: 1.7; 95% CI: 1.3-2.1) compared with those who did not.ConclusionsAcute cardiac events were common during COVID-19-associated hospitalizations, particularly among patients with underlying cardiac disease, and are associated with severe disease outcomes. Persons at greater risk for experiencing acute cardiac events during COVID-19-associated hospitalizations might benefit from more intensive clinical evaluation and monitoring during hospitalization.     

Global Circumferential and Radial Strain Among Patients With Immune Checkpoint Inhibitor Myocarditis

BackgroundGlobal circumferential strain (GCS) and global radial strain (GRS) are reduced with cytotoxic chemotherapy. There are limited data on the effect of immune checkpoint inhibitor (ICI) myocarditis on GCS and GRS.ObjectivesThis study aimed to detail the role of GCS and GRS in ICI myocarditis.MethodsIn this retrospective study, GCS and GRS from 75 cases of patients with ICI myocarditis and 50 ICI-treated patients without myocarditis (controls) were compared. Pre-ICI GCS and GRS were available for 12 cases and 50 controls. Measurements were performed in a core laboratory blinded to group and time. Major adverse cardiovascular events (MACEs) were defined as a composite of cardiogenic shock, cardiac arrest, complete heart block, and cardiac death.ResultsCases and controls were similar in age (66 ± 15 years vs 63 ± 12 years; P = 0.20), sex (male: 73% vs 61%; P = 0.20) and cancer type (P = 0.08). Pre-ICI GCS and GRS were also similar (GCS: 22.6% ± 3.4% vs 23.5% ± 3.8%; P = 0.14; GRS: 45.5% ± 6.2% vs 43.6% ± 8.8%; P = 0.24). Overall, 56% (n = 42) of patients with myocarditis presented with preserved left ventricular ejection fraction (LVEF). GCS and GRS were lower in myocarditis compared with on-ICI controls (GCS: 17.5% ± 4.2% vs 23.6% ± 3.0%; P < 0.001; GRS: 28.6% ± 6.7% vs 47.0% ± 7.4%; P < 0.001). Over a median follow-up of 30 days, 28 cardiovascular events occurred. A GCS (HR: 4.9 [95% CI: 1.6-15.0]; P = 0.005) and GRS (HR: 3.9 [95% CI: 1.4-10.8]; P = 0.008) below the median was associated with an increased event rate. In receiver-operating characteristic (ROC) curves, GCS (AUC: 0.80 [95% CI: 0.70-0.91]) and GRS (AUC: 0.76 [95% CI: 0.64-0.88]) showed better performance than cardiac troponin T (cTnT) (AUC: 0.70 [95% CI: 0.58-0.82]), LVEF (AUC: 0.69 [95% CI: 0.56-0.81]), and age (AUC: 0.54 [95% CI: 0.40-0.68]). Net reclassification index and integrated discrimination improvement demonstrated incremental prognostic utility of GRS over LVEF (P = 0.04) and GCS over cTnT (P = 0.002).ConclusionsGCS and GRS are lower in ICI myocarditis, and the magnitude of reduction has prognostic significance.     

Impact of Subintimal Plaque Modification on Reattempted Chronic Total Occlusions Percutaneous Coronary Intervention

BackgroundPredictors of success in reattempted chronic total occlusion (CTO) percutaneous coronary intervention (PCI) procedures remain obscure, mainly owing to the lack of consecutive angiograms and procedural records of initial attempts in the same cohort.ObjectivesThis study sought to investigate the factors predicting the success of reattempted CTO PCI procedures.MethodsA total of 208 consecutive patients who underwent a failed CTO PCI attempt and received reattempted procedure at the same cardiac center were retrospectively analyzed. Predictors of the success of reattempted procedures were evaluated.ResultsThe overall technical success rate of reattempted CTO PCI procedures was 71.2%. Subintimal plaque modification (SPM) was implemented in 35 (16.8%) procedures in initial attempts. The reattempted technical success rate was 93.3% in cases in which SPM with guidewire (GW) crossing was achieved in the initial attempt; however, the success rate was 55.0% for procedures involving SPM without GW crossing. SPM with GW crossing (OR: 11.21; 95% CI: 1.31-96.16; P = 0.028), referral to high-volume operators (OR: 2.38; 95% CI: 1.14-4.98; P = 0.021), and a bidirectional approach (OR: 2.31; 95% CI: 1.12-4.79; P = 0.024) were positive independent predictors of technical success in the subsequent reattempt. The time interval for reattempt (per 90-day increment) was negatively correlated with the technical success of the reattempted procedures (OR: 0.85; 95% CI: 0.73-0.98; P = 0.030).ConclusionsThis study identified independent predictors of success in reattempted CTO PCI procedures. SPM with GW crossing achieved in the initial attempt is associated with a higher success rate in the subsequent reattempt.     

Prognostic Value of Late Gadolinium Enhancement Detected on Cardiac Magnetic Resonance in Cardiac Sarcoidosis

BackgroundSarcoidosis is a complex multisystem inflammatory disorder, with approximately 5% of patients having overt cardiac involvement. Patients with cardiac sarcoidosis are at an increased risk of both ventricular arrhythmias and sudden cardiac death. Previous studies have shown that the presence of late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is associated with an increased risk of mortality and ventricular arrhythmias and may be useful in predicting prognosis.ObjectivesThis systematic review and meta-analysis assessed the value of LGE on CMR imaging in predicting prognosis for patients with known or suspected cardiac sarcoidosis.MethodsThe authors searched the Embase and MEDLINE databases from inception to March 2022 for studies reporting individuals with known or suspected cardiac sarcoidosis referred for CMR with LGE. Outcomes were defined as all-cause mortality, ventricular arrhythmia, or a composite outcome of either death or ventricular arrhythmias. The primary analysis evaluated these outcomes according to the presence of LGE. A secondary analysis evaluated outcomes specifically according to the presence of biventricular LGE.ResultsThirteen studies were included (1,318 participants) in the analysis, with an average participant age of 52.0 years and LGE prevalence of 13% to 70% over a follow-up of 3.1 years. Patients with LGE on CMR vs those without had higher odds of ventricular arrhythmias (odds ratio [OR]: 20.3; 95% CI: 8.1-51.0), all-cause mortality (OR: 3.45; 95% CI: 1.6-7.3), and the composite of both (OR: 9.2; 95% CI: 5.1-16.7). Right ventricular LGE is invariably accompanied by left ventricular LGE. Biventricular LGE is also associated with markedly increased odds of ventricular arrhythmias (OR: 43.6; 95% CI: 16.2-117.2).ConclusionsPatients with known or suspected cardiac sarcoidosis with LGE on CMR have significantly increased odds of both ventricular arrhythmias and all-cause mortality. The presence of biventricular LGE may confer additional prognostic information regarding arrhythmogenic risk.     

Diagnostic and Prognostic Role of Cardiac Magnetic Resonance in MINOCA: Systematic Review and Meta-Analysis

BackgroundMyocardial infarction with nonobstructive coronary arteries (MINOCA) is common in current clinical practice. Cardiac magnetic resonance (CMR) plays an important role in its management and is increasingly recommended by all the current guidelines. However, the prognostic value of CMR in patients with MINOCA is still undetermined.ObjectivesThe purpose of this study was to determine the diagnostic and prognostic value of CMR in the management of patients with MINOCA.MethodsA systematic review was performed to identify studies reporting the results of CMR findings in patients with MINOCA. Random effects models were used to determine the prevalence of different disease entities: myocarditis, myocardial infarction (MI), or takotsubo syndrome. Pooled odds ratios (ORs) and 95% CIs were calculated to evaluate the prognostic value of CMR diagnosis in the subgroup of studies that reported clinical outcomes.ResultsA total of 26 studies comprising 3,624 patients were included. The mean age was 54.2 ± 5.3 years, and 56% were men. MINOCA was confirmed in only 22% (95% CI: 0.17-0.26) of the cases and 68% of patients with initial MINOCA were reclassified after the CMR assessment. The pooled prevalence of myocarditis was 31% (95% CI: 0.25-0.39), and takotsubo syndrome 10% (95% CI: 0.06-0.12). In a subgroup analysis of 5 studies (770 patients) that reported clinical outcomes, CMR diagnosis of confirmed MI was associated with an increased risk of major adverse cardiovascular events (pooled OR: 2.40; 95% CI: 1.60-3.59).ConclusionsIn patients with MINOCA, CMR has been demonstrated to add an important diagnostic and prognostic value, proving to be crucial for the diagnosis of this condition. Sixty-eight percent of patients with initial MINOCA were reclassified after the CMR evaluation. CMR-confirmed diagnosis of MINOCA was associated with an increased risk of major adverse cardiovascular events at follow-up.     

Prognostic Value of Stress CMR in Symptomatic Patients With Coronary Stenosis on CCTA

BackgroundNoninvasive functional imaging is often performed in patients with obstructive coronary artery disease (CAD) on coronary computed tomography angiography (CTA). However, the prognostic value of stress cardiac magnetic resonance (CMR) is unknown in patients with coronary stenosis of unknown significance on coronary CTA.ObjectivesThis study assessed the prognostic value of stress CMR in symptomatic patients with obstructive CAD of unknown significance on coronary CTA.MethodsBetween 2008 and 2020, consecutive symptomatic patients without known CAD referred for coronary CTA were screened. Patients with obstructive CAD (at least 1 ≥50% stenosis on coronary CTA) were further referred for stress CMR and followed for the occurrence of major adverse cardiovascular events (MACEs), defined as cardiovascular death or nonfatal myocardial infarction.ResultsOf 2,210 patients who completed CMR, 2,038 (46.5% men; mean age 69.8 ± 12.2 years) completed follow-up (median 6.8 years; IQR: 5.9-9.2 years); 281 experienced a MACE (13.8%). Inducible ischemia and late gadolinium enhancement (LGE) were significantly associated with MACEs (HR: 4.51 [95% CI: 3.55-5.74], and HR: 3.32 [95% CI: 2.55-4.32], respectively; P < 0.001). In multivariable Cox regression, the number of segments with >70% stenosis, with noncalcified plaques and the number of vessels with obstructive CAD were prognosticators (P < 0.001). The presence of inducible ischemia and LGE were independent predictors of MACEs (HR: 3.97 [95% CI: 3.43-5.13]; HR: 2.30 [95% CI: 1.52-3.33]; P < 0.001). After adjustment, stress CMR showed the best improvement in model discrimination and reclassification above traditional risk factors and coronary CTA (C-statistic improvement: 0.04; net reclassification improvement = 0.421; integrative discrimination index = 0.047).ConclusionsIn symptomatic patients with obstructive CAD of unknown significance on coronary CTA, stress CMR had incremental prognostic value to predict MACEs.     

Transcaval Versus Transaxillary TAVR in Contemporary Practice: A Propensity-Weighted Analysis

ObjectivesThe aim of this study was to compare transcaval and transaxillary artery access for transcatheter aortic valve replacement (TAVR) at experienced medical centers in contemporary practice.BackgroundThere are no systematic comparisons of transcaval and transaxillary TAVR access routes.MethodsEight experienced centers contributed local data collected for the STS/ACC TVT Registry (Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry) between 2017 and 2020. Outcomes after transcaval and axillary/subclavian (transaxillary) access were adjusted for baseline imbalances using doubly robust (inverse propensity weighting plus regression) estimation and compared.ResultsTranscaval access was used in 238 procedures and transaxillary access in 106; for comparison, transfemoral access was used in 7,132 procedures. Risk profiles were higher among patients selected for nonfemoral access but similar among patients requiring transcaval and transaxillary access. Stroke and transient ischemic attack were 5-fold less common after transcaval than transaxillary access (2.5% vs 13.2%; OR: 0.20; 95% CI: 0.06-0.72; P = 0.014) compared with transfemoral access (1.7%). Major and life-threatening bleeding (Valve Academic Research Consortium 3 ≥ type 2) were comparable (10.0% vs 13.2%; OR: 0.66; 95% CI: 0.26-1.66; P = 0.38) compared with transfemoral access (3.5%), as was blood transfusion (19.3% vs 21.7%; OR: 1.07; 95% CI: 0.49-2.33; P = 0.87) compared with transfemoral access (7.1%). Vascular complications, intensive care unit and hospital length of stay, and survival were similar between transcaval and transaxillary access. More patients were discharged directly home and without stroke or transient ischemic attack after transcaval than transaxillary access (87.8% vs 62.3%; OR: 5.19; 95% CI: 2.45-11.0; P < 0.001) compared with transfemoral access (90.3%).ConclusionsPatients undergoing transcaval TAVR had lower rates of stroke and similar bleeding compared with transaxillary access in a contemporary experience from 8 US centers. Both approaches had more complications than transfemoral access. Transcaval TAVR access may offer an attractive option.     

Retrograde Chronic Total Occlusion Percutaneous Coronary Interventions: Predictors of Procedural Success From the ERCTO Registry

ObjectivesThe aim of this study was to identify independent predictors of procedural success after retrograde chronic total occlusion (CTO) percutaneous coronary intervention (PCI).BackgroundRetrograde CTO PCI is an established technique, but predictors of success remain poorly understood.MethodsA multivariable logistic regression model was used to analyze potentially important demographic, clinical, anatomical, and technical aspects of retrograde CTO PCI cases uploaded to the multicenter European CTO (ERCTO) Club Registry.ResultsIn calendar years 2018 and 2019, 2,364 retrograde CTO PCI cases constituted the primary analysis cohort. A primary retrograde strategy was used in 1,953 cases (82.6%), and an initial antegrade approach was converted to retrograde in 411 cases (17.4%). Procedural success was achieved in 1,820 cases (77.0%) and was more likely to occur after a primary retrograde attempt versus conversion from an initial antegrade approach (80.9% vs 58.4%; P < 0.0001). After multivariable analysis, an absence of lesion calcification (OR: 1.86; 95% CI: 1.37-2.51; P < 0.0001), a higher degree of distal vessel opacification (OR: 2.47; 95% CI: 1.72-3.55; P < 0.0001), little or no proximal target vessel tortuosity (OR: 1.84; 95% CI: 1.28-2.64; P = 0.001), Werner collateral connection CC1 (OR: 4.87; 95% CI: 2.90-8.19; P < 0.0001) or CC2 (OR: 5.33; 95% CI: 3.02-9.42; P < 0.0001), and the top tertile of operator volume (>120 cases over 2 years) (OR: 1.88; 95% CI: 1.26-2.79; P = 0.002) were associated with the greatest chance of achieving angiographic success.ConclusionsLess calcification with good distal vessel opacification, little or absent proximal vessel tortuosity, and visible collateral connections, along with high-volume operator status, were all independently predictive of angiographically successful retrograde CTO PCI.     

Comparative Safety of Transcatheter LAAO With the First-Generation Watchman and Next-Generation Watchman FLX Devices

BackgroundProcedural complications limit the clinical benefit of transcatheter left atrial appendage occlusion (LAAO). Next-generation devices incorporate design modifications intended to improve procedural safety, but their clinical impact has not been described.ObjectivesThe aim of this study was to compare in-hospital outcomes for the Watchman FLX with the predicate Watchman 2.5 device.MethodsThe National Cardiovascular Data Registry LAAO Registry was used to identify patients who received the Watchman FLX and an identical number of patients receiving the Watchman 2.5 at the same sites directly preceding the first Watchman FLX case at each site. The primary endpoint was in-hospital major adverse events (MAE), defined as a composite of death, cardiac arrest, stroke, transient ischemic attack, intracranial hemorrhage, systemic arterial embolism, major bleeding, major vascular complication, myocardial infarction, pericardial effusion requiring intervention (percutaneous or surgical), and device embolization. A secondary analysis was performed using 2:1 propensity score matching of patients receiving the Watchman 2.5 or Watchman FLX.ResultsThe study cohort consisted of 27,013 patients receiving each device. The rate of in-hospital MAE was significantly lower for the Watchman FLX compared with the Watchman 2.5 (1.35% vs 2.40%; adjusted OR: 0.57; 95% CI: 0.50-0.65; P < 0.0001), driven largely by fewer pericardial effusions requiring intervention (0.42% vs 1.23%; adjusted OR: 0.34; 95% CI: 0.28-0.42; P < 0.0001). The Watchman FLX was also associated with significant lower rates of the individual endpoints of in-hospital mortality (0.12% vs 0.24%; P < 0.0001), major bleeding (1.08% vs 2.05%; P < 0.0001), cardiac arrest (0.13% vs 0.24%; P = 0.006), and device embolization (0.02% vs 0.06%; P = 0.028), while myocardial infarction, stroke, and major vascular complications did not differ between groups. Propensity score matching analysis demonstrated similar results, with lower rates of MAE with the Watchman FLX (1.34% vs 2.58%; OR: 0.51; 95% CI: 0.46-0.58; P < 0.0001).ConclusionsTranscatheter LAAO with the Watchman FLX was associated with lower rates of in-hospital MAE compared with the predicate Watchman device, including mortality, pericardial effusion, major bleeding, cardiac arrest, and device embolization. This may favorably influence the balance of risks and benefits of transcatheter LAAO for stroke prevention in patients with atrial fibrillation.     

Association of Regional Wall Shear Stress and Progressive Ascending Aorta Dilation in Bicuspid Aortic Valve

ObjectivesThe aim of this study was to evaluate the role of wall shear stress (WSS) as a predictor of ascending aorta (AAo) growth at 5 years or greater follow-up.BackgroundAortic 4-dimensional flow cardiac magnetic resonance (CMR) can quantify regions exposed to high WSS, a known stimulus for arterial wall dysfunction. However, its association with longitudinal changes in aortic dilation in patients with bicuspid aortic valve (BAV) is unknown.MethodsThis retrospective study identified 72 patients with BAV (age 45 ± 12 years) who underwent CMR for surveillance of aortic dilation at baseline and ≥5 years of follow-up. Four-dimensional flow CMR analysis included the calculation of WSS heat maps to compare regional WSS in individual patients with population averages of healthy age- and sex-matched subjects (database of 136 controls). The relative areas of the AAo and aorta (in %) exposed to elevated WSS (outside the 95% CI of healthy population averages) were quantified.ResultsAt a median follow-up duration of 6.0 years, the mean AAo growth rate was 0.24 ± 0.20 mm/y. The fraction of the AAo exposed to elevated WSS at baseline was increased for patients with higher growth rates (>0.24 mm/y, n = 32) compared with those with growth rates <0.24 mm/y (19.9% [IQR: 10.2%-25.5%] vs 5.7% [IQR: 1.5%-21.3%]; P = 0.008). Larger areas of elevated WSS in the AAo and entire aorta were associated with higher rates of AAo dilation >0.24 mm/y (odds ratio: 1.51; 95% CI: 1.05-2.17; P = 0.026 and odds ratio: 1.70; 95% CI: 1.01-3.15; P = 0.046, respectively).ConclusionsThe area of elevated AAo WSS as assessed by 4-dimensional flow CMR identified BAV patients with higher rates of aortic dilation and thus might determine which patients require closer follow-up.     

Clonal Hematopoiesis and Risk of Progression of Heart Failure With Reduced Left Ventricular Ejection Fraction

BackgroundClonal hematopoiesis driven by somatic mutations in hematopoietic cells, frequently called clonal hematopoiesis of indeterminate potential (CHIP), has been associated with adverse cardiovascular outcomes in population-based studies and in patients with ischemic heart failure (HF) and reduced left ventricular ejection fraction (LVEF). Yet, the impact of CHIP on HF progression, including nonischemic etiology, is unknown.ObjectivesThe purpose of this study was to assess the clinical impact of clonal hematopoiesis on HF progression irrespective of its etiology.MethodsThe study cohort comprised 62 patients with HF and LVEF <45% (age 74 ± 7 years, 74% men, 52% nonischemic, and LVEF 30 ± 8%). Deep sequencing was used to detect CHIP mutations with a variant allelic fraction >2% in 54 genes. Patients were followed for at least 3.5 years for various adverse events including death, HF-related death, and HF hospitalization.ResultsCHIP mutations were detected in 24 (38.7%) patients, without significant differences in all-cause mortality (p = 0.151). After adjusting for risk factors, patients with mutations in either DNA methyltransferase 3 alpha (DNMT3A) or Tet methylcytosine dioxygenase 2 (TET2) exhibited accelerated HF progression in terms of death (hazard ratio [HR]: 2.79; 95% confidence interval [CI]: 1.31 to 5.92; p = 0.008), death or HF hospitalization (HR: 3.84; 95% CI: 1.84 to 8.04; p < 0.001) and HF-related death or HF hospitalization (HR: 4.41; 95% CI: 2.15 to 9.03; p < 0.001). In single gene-specific analyses, somatic mutations in DNMT3A or TET2 retained prognostic significance with regard to HF-related death or HF hospitalization (HR: 4.50; 95% CI: 2.07 to 9.74; p < 0.001, for DNMT3A mutations; HR: 3.18; 95% CI: 1.52 to 6.66; p = 0.002, for TET2 mutations). This association remained significant irrespective of ischemic/nonischemic etiology.ConclusionsSomatic mutations that drive clonal hematopoiesis are common among HF patients with reduced LVEF and are associated with accelerated HF progression regardless of etiology.     

Prognostic Value of Right Ventricular Function in Patients With Suspected Myocarditis Undergoing Cardiac Magnetic Resonance

BackgroundRisk-stratification of myocarditis is based on functional parameters and tissue characterization of the left ventricle (LV), whereas right ventricular (RV) involvement remains mostly unrecognized.ObjectivesIn this study, the authors sought to analyze the prognostic value of RV involvement in myocarditis by cardiac magnetic resonance (CMR).MethodsPatients meeting the recommended clinical criteria for suspected myocarditis were enrolled at 2 centers. Exclusion criteria were the evidence of coronary artery disease, pulmonary artery hypertension or structural cardiomyopathy. Biventricular ejection fraction, edema according to T2-weighted images, and late gadolinium enhancement (LGE) were linked to a composite end point of major adverse cardiovascular events (MACE), including heart failure hospitalization, ventricular arrhythmia, recurrent myocarditis, and death.ResultsAmong 1,125 consecutive patients, 736 (mean age: 47.8 ± 16.1 years) met the clinical diagnosis of suspected myocarditis and were followed for 3.7 years. Signs of RV involvement (abnormal right ventricular ejection fraction [RVEF], RV edema, and RV-LGE) were present in 188 (25.6%), 158 (21.5%), and 92 (12.5%) patients, respectively. MACE occurred in 122 patients (16.6%) and was univariably associated with left ventricular ejection fraction (LVEF), LV edema, LV-LGE, RV-LGE, RV edema, and RVEF. In a series of nesting multivariable Cox regression models, the addition of RVEF (HR_adj: 0.974 [95% CI: 0.956-0.993]; P = 0.006) improved prognostication (chi-square test = 89.5; P = 0.001 vs model 1; P = 0.006 vs model 2) compared with model 1 including only clinical variables (chi-square test = 28.54) and model 2 based on clinical parameters, LVEF, and LV-LGE extent (chi-square test = 78.93).ConclusionsThis study emphasizes the role of RV involvement in myocarditis and demonstrates the independent and incremental prognostic value of RVEF beyond clinical variables, CMR tissue characterization, and LV function. (Inflammatory Cardiomyopathy Bern Registry [FlamBER]; NCT04774549; CMR Features in Patients With Suspected Myocarditis [CMRMyo]; NCT03470571)     

Diagnostic and Prognostic Value of Myocardial Work Indices for Identification of Cancer Therapy–Related Cardiotoxicity

BackgroundEchocardiographic global longitudinal strain (GLS) is a useful measure for detection of cancer treatment–related cardiac dysfunction (CTRCD) but is influenced by blood pressure changes. This limitation may be overcome by assessment of myocardial work (MW), which incorporates blood pressure into the calculation.ObjectivesThis work aims to determine whether myocardial work indices (MWIs) can help diagnose or prognosticate CTRCD.MethodsIn this prospective cohort study, 136 women undergoing anthracycline and trastuzumab treatment for HER2+ breast cancer, underwent serial echocardiograms and cardiac magnetic resonance pre- and post-anthracycline and every 3 months during trastuzumab. GLS, global work index (GWI), global constructive work (GCW), global wasted work, and global work efficiency were measured. CTRCD was defined with cardiac magnetic resonance. Generalized estimating equations quantified the association between changes in GLS and MWIs and CTRCD at the current (diagnosis) and subsequent visit (prognosis). Regression tree analysis was used to explore the combined use of GLS and MW for the diagnostic/prognostic assessment of CTRCD.ResultsBaseline left ventricular ejection fraction (LVEF) was 63.2 ± 4.0%. Thirty-seven (27.2%) patients developed CTRCD. An absolute change in GLS (standardized odds ratio [sOR]: 1.97 [95% CI: 1.07-3.66]; P = 0.031) and GWI (sOR: 1.73 [95% CI: 1.04-2.85]; P = 0.033) were associated with concurrent CTRCD. An absolute change in GLS (sOR: 1.79 [95% CI: 1.22-2.62]; P = 0.003), GWI (sOR: 1.67 [95% CI: 1.20-2.32]; P = 0.003), and GCW (sOR: 1.65 [95% CI: 1.17-2.34]; P = 0.005) were associated with subsequent CTRCD. Change in GWI and GCW demonstrated incremental value over GLS and clinical factors for the diagnosis of concurrent CTRCD. In a small group with a GLS change <3.3% (absolute), and a >21 mm Hg reduction in systolic blood pressure, worsening of GWI identified patients with higher probability of concurrent CTRCD (24.0% vs 5.2%). MWIs did not improve identification of subsequent CTRCD beyond knowledge of GLS change.ConclusionsGLS can be used to diagnose and prognosticate cardiac magnetic resonance (CMR) defined CTRCD, with additional value from MWIs in selected cases. (Evaluation of Myocardial Changes During Breast Adenocarcinoma Therapy to Detect Cardiotoxicity Earlier With MRI [EMBRACE-MRI]; NCT02306538)     

Native T1 Mapping,Extracellular Volume Mapping,and Late Gadolinium Enhancement in Cardiac Amyloidosis: A Meta-Analysis

ObjectivesThis study aimed to compare the diagnostic and prognostic performance of native T1 mapping (T1), extracellular volume (ECV) mapping, and late gadolinium enhancement (LGE) imaging for evaluating cardiac amyloidosis (CA).BackgroundCA is a progressive infiltrative process in the extracellular space that is often underdiagnosed and holds a poor prognosis. Cardiac magnetic resonance (CMR) offers novel techniques for detecting and quantifying the disease burden of CA.MethodsWe searched PubMed for published studies using native T1, ECV, or LGE to diagnose and prognosticate CA. A total of 18 diagnostic (n = 2,015) and 13 prognostic studies (n = 1,483) were included for analysis. Pooled sensitivities, specificities, diagnostic odds ratios (DORs) of all diagnostic tests were assessed by bivariate analysis. Pooled hazard ratios (HRs) for mortality for the 3 techniques were determined.ResultsBivariate comparison showed that ECV (DOR: 84.6; 95% confidence interval [CI]: 30.3 to 236.2) had a significantly higher DOR for CA than LGE (DOR: 20.1; 95% CI: 9.1 to 44.1; p = 0.03 vs. ECV). There was no significant difference between LGE and native T1 for sensitivity, specificity, and DOR. HR was significantly higher for ECV (HR: 4.27; 95% CI: 2.87 to 6.37) compared with LGE (HR: 2.60; 95% CI: 1.90 to 3.56; p = 0.03 vs. ECV) and native T1 (HR: 2.04; 95% CI: 1.24 to 3.37; p = 0.01 vs. ECV).ConclusionsECV demonstrates a higher diagnostic OR for assessing cardiac amyloid than LGE and a higher HR for adverse events compared with LGE and native T1. In addition, native T1 showed similar sensitivity and specificity as ECV and LGE without requiring contrast material. Although limited by study heterogeneity, this meta-analysis suggests that ECV provides high diagnostic and prognostic utility for the assessment of cardiac amyloidosis.     

Clopidogrel Monotherapy After 1-Month Dual Antiplatelet Therapy in Patients With Diabetes Undergoing Percutaneous Coronary Intervention

BackgroundDiabetes was reported to be associated with an impaired response to clopidogrel.ObjectivesThe aim of this study was to evaluate the safety and efficacy of clopidogrel monotherapy after very short dual antiplatelet therapy (DAPT) in patients with diabetes undergoing percutaneous coronary intervention (PCI).MethodsA subgroup analysis was conducted on the basis of diabetes in the STOPDAPT-2 (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent–2) Total Cohort (N = 5,997) (STOPDAPT-2, n = 3,009; STOPDAPT-2 ACS [Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent–2 for the Patients With ACS], n = 2,988), which randomly compared 1-month DAPT followed by clopidogrel monotherapy with 12-month DAPT with aspirin and clopidogrel after cobalt-chromium everolimus-eluting stent implantation. The primary endpoint was a composite of cardiovascular (cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) or bleeding (TIMI [Thrombolysis In Myocardial Infarction] major or minor) endpoints at 1 year.ResultsThere were 2,030 patients with diabetes (33.8%) and 3967 patients without diabetes (66.2%). Regardless of diabetes, the risk of 1-month DAPT relative to 12-month DAPT was not significant for the primary endpoint (diabetes, 3.58% vs 4.12% [HR: 0.87; 95% CI: 0.56-1.37; P = 0.55]; nondiabetes, 2.46% vs 2.49% [HR: 0.99; 95% CI: 0.67-1.48; P = 0.97]; P_interaction = 0.67) and for the cardiovascular endpoint (diabetes, 3.28% vs 3.05% [HR: 1.10; 95% CI: 0.67-1.81; P = 0.70]; nondiabetes, 1.95% vs 1.43% [HR: 1.38; 95% CI: 0.85-2.25; P = 0.20]; P_interaction = 0.52), while it was lower for the bleeding endpoint (diabetes, 0.30% vs 1.50% [HR: 0.20; 95% CI: 0.06-0.68; P = 0.01]; nondiabetes, 0.61% vs 1.21% [HR: 0.51; 95% CI: 0.25-1.01; P = 0.054]; P_interaction = 0.19).ConclusionsClopidogrel monotherapy after 1-month DAPT compared with 12-month DAPT reduced major bleeding events without an increase in cardiovascular events regardless of diabetes, although the findings should be considered as hypothesis generating, especially in patients with acute coronary syndrome, because of the inconclusive result in the STOPDAPT-2 ACS trial. (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent–2 [STOPDAPT-2], NCT02619760; Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent–2 for the Patients With ACS [STOPDAPT-2 ACS], NCT03462498)     

Thrombotic Risk and Cardiovascular Events in Patients With Revascularization Deferral After Fractional Flow Reserve Assessment

ObjectivesThe aim of this study was to evaluate the impact of thrombotic risk on the occurrence of cardiovascular events in patients with coronary artery disease with deferred revascularization after fractional flow reserve (FFR) measurements.BackgroundDeferral of revascularization on the basis of FFR is generally considered to be safe, but after deferral, some patients have cardiovascular events over time.MethodsFrom J-CONFIRM registry (Long-Term Outcomes of Japanese Patients With Deferral of Coronary Intervention Based on Fractional Flow Reserve in Multicenter Registry), 1,263 patients with deferral of revascularization on the basis of FFR were evaluated. The association between thrombotic risk as assessed by CREDO-Kyoto (Coronary Revascularization Demonstrating Outcome Study in Kyoto) thrombotic score and 5-year target vessel failure (TVF) and major adverse cardiac and cerebrovascular events (MACCE) was investigated.ResultsFFR and high thrombotic risk (HTR) were associated with increased risk for 5-year TVF (FFR per 0.01-unit decrease: HR: 1.08; 95% CI: 1.05-1.11; P < 0.001; HTR: HR: 2.16; 95% CI: 1.37-3.39; P < 0.001) and MACCE (FFR per 0.01-unit decrease: HR: 1.05; 95% CI: 1.02-1.06; P < 0.001; HTR: HR: 2.11; 95% CI: 1.56-2.84; P = 0.001). Patients with HTR had higher risk for 5-year TVF (HR: 2.30; 95% CI: 1.45-3.66; P < 0.001) and MACCE (HR: 2.34; 95% CI: 1.75-3.13; P < 0.001) than those without HTR, even when they had negative FFR.ConclusionsAssessment of thrombotic risk provides additional prognostic value to FFR in predicting 5-year TVF and MACCE in patients with deferral of revascularization after FFR measurements. (Long-Term Outcomes of Japanese Patients With Deferral of Coronary Intervention Based on Fractional Flow Reserve in Multicenter Registry; UMIN000014473)