Optimizing Percutaneous Mitral Valvuloplasty for Rheumatic Mitral Stenosis　- Clinical Significance of Changes in Mitral Valve Area.

BACKGROUND: Percutaneous mitral valvuloplasty (PMV) is a standard treatment for severe rheumatic mitral stenosis (RMS). However, the prognostic significance of the change in mitral valve area (∆MVA) during PMV is not fully understood.Methods and Results: This study analyzed data from the Multicenter mitrAl STEnosis with Rheumatic etiology (MASTER) registry, which included 3,140 patients with severe RMS. We focused on patients with severe RMS undergoing their first PMV. Changes in echocardiographic parameters, including MVA quantified before and after PMV, and composite outcomes, including mitral valve reintervention, heart failure admission, stroke, and all-cause death, were evaluated. An optimal result was defined as a postprocedural MVA ≥1.5 cm2without mitral regurgitation greater than Grade II. Of the 308 patients included in the study, those with optimal results and ∆MVA >0.5 cm² had a better prognosis (log-rank P<0.001). Patients who achieved optimal results but with ∆MVA ≤0.5 cm² had a greater risk of composite outcomes than those with optimal outcomes and ∆MVA >0.5 cm² (nested Cox regression analysis, hazard ratio 2.27; 95% confidence interval 1.09-4.73; P=0.028). CONCLUSIONS: Achieving an increase in ∆MVA of >0.5 cm2was found to be correlated with improved outcomes. This suggests that, in addition to achieving traditional optimal results, targeting an increase in ∆MVA of >0.5 cm2could be a beneficial objective in PMV treatment for RMS.

Shifts in Clinical Characteristics, Treatment, and Outcome for Rheumatic Mitral Stenosis: Insights From a 20-Year Multicentre Registry Study in Korea.

BACKGROUND: The rapid economic development of South Korea provides a unique model to study changes in the clinical characteristics, treatment approaches, and clinical outcomes of patients with rheumatic mitral stenosis (MS) relative to socioeconomic growth. METHODS: From the Multicenter mitrAl STEnosis with Rheumatic etiology (MASTER) registry, 2,337 patients diagnosed with moderate or severe rheumatic MS between January 2001 and December 2020 were analyzed. Patients were grouped into consecutive 5-year intervals based on their year of diagnosis. Clinical characteristics, echocardiographic data, and clinical outcomes were assessed. RESULTS: Over 20 years, the severity of mitral stenosis increased from 79.1% to 90.2%; similarly, the average age at diagnosis increased from 54.3 to 63.0 years (all P < 0.001). Comorbidities such as hypertension and atrial fibrillation increased (6.3% to 29.5% and 41.4% to 46.9%, respectively; all P for trend < 0.05). The rate of mitral intervention within five years after diagnosis increased from 31.2% to 47.4% (P for trend < 0.001). However, clinical outcomes of rheumatic mitral stenosis deteriorated over time in the composite outcomes (log-rank test, P < 0.001). Conversely, the incidence of stroke remained stable (60.6-73.7%; P < 0.001), which might be attributed to the increased use of anticoagulation therapy. CONCLUSION: This study observed an increase in patient age, comorbidities, and valve disease severity as the country transitioned from a developing to developed status. Despite a rise in mitral valve interventions, clinical outcomes deteriorated over 20 years, highlighting the need for modified treatment approaches to improve patient outcomes.

The Impact of Different Cooking Methods on the Flavor Profile of Fermented Chinese Spicy Cabbage.

Chinese spicy cabbage (CSC) is a common traditional fermented vegetable mainly made of Chinese cabbage. In addition to eating raw, boiling and stir-frying are the most common cooking methods for CSC. To identify the impacts of boiling or stir-frying on the quality of CSC, the physicochemical properties, flavor compounds, and sensory properties of CSC were analyzed. A total of 47 volatile flavor compounds (VFCs) were detected by gas chromatography-mass spectrometry. Sulfide was determined as the main flavor compound of CSC, mainly contributed by cabbage, garlic, and onion odors. The content of sulfide decreased significantly after cooking. Nonanal, geranyl acetate, and linalool were newly generated after boiling with odor activity value (OAV) > 1, and contributed fatty, sweet, fruity, and floral odors to BL-CSC. 1-Octen-3-one, 1-octen-3-ol, octanal, nonanal, and (E)-2-nonenal were newly generated after stir-frying with OAV > 1, and contributed mushroom, fatty, and green odors to SF-CSC. Diallyl trisulfide, nonanal, (E)-ß-ionone, ß-sesquiphellandrene, and (E)-2-decenal were considered as the potential key aroma compounds (KACs) to distinguish the CSCs after different heat treatment. After cooking, the total titratable acidity of CSC increased and the sensory properties changed significantly. This study provides valuable information and guidance on the sensory and flavor changes of thermal processing fermented vegetables.

Characteristics and outcomes of heart transplant recipients with a pretransplant history of malignancy.

We aimed to investigate the characteristics and outcomes of HTx recipients with a history of pretransplant malignancy (PTM). Among 1062 HTx recipients between 1997 and 2013, 73 (7.1%) patients had PTMs (77 cancer cases). We analyzed post-HTx outcome, recurrence of PTM, and development of de novo malignancies. Post-HTx outcome included overall survival, 10-year survival, 10-year freedom from cardiac allograft vasculopathy (CAV), non-fatal major adverse cardiac events (NF-MACE), any treated rejection (ATR), acute cellular rejection (ACR), and antibody-mediated rejection (AMR). Four most common PTMs were lymphoproliferative disorders (18.2%), prostate cancers (18.2%), non-melanoma skin cancers (18.2%), and breast cancers (13.0%). Median time from PTM and HTx was 9.0 years. During a median follow-up of 8.6 years after HTx, patients with PTM, compared to those without, showed significantly higher incidence of posttransplant malignancies (43.8% vs. 20.8%, p < .001) including 9.6% (n = 7) of PTM recurrences. However, patients with PTM, compared to those without, showed comparable overall survival, 10-year survival, 10-year freedom from CAV, NF-MACE, ATR, ACR, and AMR. Therefore, a history of PTM should not disqualify patients from HTx listing, while further research is necessary for early detection of posttransplant malignancies in these patients.

Ability of soluble ST2 to predict left ventricular remodeling in patients with acute coronary syndrome.

The association of the soluble suppression of tumorigenicity 2 (sST2) and the prognosis of heart failure have been well evaluated. However, little is known about the prediction of sST2 for left ventricular (LV) remodeling in acute coronary syndrome (ACS). We investigated the ability of sST2 to predict LV remodeling following the revascularization of ACS. From May 2019 to December 2020, 95 patients with LV ejection fraction (EF) < 50% who underwent coronary revascularization for ACS (unstable angina, non-ST-elevation myocardial infarction, ST-elevation myocardial infarction) were enrolled. Echocardiography and sST2 were performed at baseline and at a 3-month follow-up. The association between LV remodeling, using the end-diastolic volume index, and sST2 at baseline and at the 3-month follow-up, and the difference between each value was explored. During follow-up, 41 patients showed LV adverse remodeling. The baseline sST2 increased in patients without adverse remodeling (32.05 ng/mL vs. 23.5 ng/mL, p < 0.001), although clinical characteristics were similar between the two groups. During the mean follow-up of 3 months, a significant correlation was found in the changes between sST2 and LV end-diastolic/systolic volume index (r = 0.649; p < 0.001, r = 0.618; p < 0.001, respectively), but not in the changes of LVEF (r = - 0.132, p = 0.204). The use of angiotensin-converting enzyme 2 inhibitors/receptor blockers was higher (90.7% vs. 53.7%, p < 0.001) and sST2 decreased more predominantly in patients without adverse remodeling (23.18 ng/mL vs 26.40 ng/mL, p = 0.003). However, the changes in sST2 and LV volume were not different according to the ACS types (p > 0.05, for all). Estimates of the odds ratio (OR) for remodeling according to the sST2 difference increased substantially with a negative increase in the sST2 difference. Multivariable analysis found that, the difference between the baseline and 3-month sST2 was the most important determinant of LV remodeling following the revascularization of ACS (OR 1.24; 95% confidence interval: 1.09 to 1.41; p = 0.001). In conclusion, an increase in sST2 during follow-up was a useful predictor of LV remodeling.

The role of cardiac CT throughout the full cardiac cycle in diagnosing patent foramen ovale in patients with acute stroke.

OBJECTIVES: We explored the hypothesis that the diagnostic performance of cardiac computed tomography (CT) throughout the full cardiac cycle would be superior to single-phase CT and comparable to transesophageal echocardiography (TEE) in diagnosing patent foramen ovale (PFO). METHODS AND RESULTS: From May 2011 to April 2015, 978 patients with stroke were diagnosed with PFO by TEE. In patients with stroke, cardiac CT was performed if the patients had more than two cardiovascular risk factors. We prospectively enrolled 70 patients with an indication for cardiac CT. Cardiac CT images were reconstructed at 10% increments of the R-R interval. The sensitivity of cardiac CT throughout the full cardiac cycle in diagnosing PFO was compared to that for TEE and single-phase cardiac CT. To evaluate the specificity of cardiac CT, we analyzed patients without PFO confirmed by TEE who underwent cardiac CT within 1 month of pre-cardiac surgery. Sixty-six patients with cardiac CT and TEE were included in the final analysis. Throughout the full cardiac cycle, cardiac CT had a sensitivity of 89.4% and a specificity of 92.3% in diagnosing PFO, compared to TEE as a reference. PFO was primarily detected in the 60% and 70% intervals in 10-phase reconstructed images. The sensitivity of PFO diagnosis with cardiac CT was 81.8% when analyzing both the 60% and 70% intervals instead of the full cardiac cycle. CONCLUSION: Cardiac CT throughout the full cardiac cycle outperforms single-phase cardiac CT in detecting PFO. Cardiac CT can be used as an alternative method to TEE for detecting PFO in stroke patients. KEY POINTS: • Throughout the full cardiac cycle, cardiac computed tomography (CT) had a sensitivity of 89.4% and a specificity of 92.3% in diagnosing patent foramen ovale (PFO), compared to transesophageal echocardiography. • The sensitivity of diagnosing patent foramen ovale with cardiac CT was 81.8% when analyzing 60% and 70% R-R intervals instead of the full cardiac cycle. • Cardiac CT with retrospective electrocardiographic gating throughout the full cardiac cycle can increase the detectability of PFO, compared to single-phase cardiac CT.

Cardiac Imaging of Acute Myocarditis Following COVID-19 mRNA Vaccination.

Increasing rates of coronavirus disease 2019 (COVID-19) vaccination coverage will result in more vaccine-related side effects, including acute myocarditis. In Korea, we present a 24-year-old male with acute myocarditis following COVID-19 vaccination (BNT162b2). His chest pain developed the day after vaccination and cardiac biomarkers were elevated. Echocardiography showed minimal pericardial effusion but normal myocardial contractility. Electrocardiography revealed diffuse ST elevation in lead II, and V2-5. Cardiac magnetic resonance images showed the high signal intensity of T2- short tau inversion recovery image, the high value of T2 mapping sequence, and late gadolinium enhancement in basal inferior and inferolateral wall. It was presumed that COVID-19 mRNA vaccination was probably responsible for acute myocarditis. Clinical course of the patient was favorable and he was discharged without any adverse event.

Atrial Fibrillation and Heart Failure with Preserved Ejection Fraction: Two Chronic Troublemakers.

In this article, the definition; mechanisms; diagnostic strategies, including scoring systems; treatments; prognosis; and future perspectives in heart failure with preserved ejection fraction with atrial fibrillation, which are common comorbid conditions, are reviewed thoroughly.

Cardiac Manifestations of Coronavirus Disease 2019 (COVID-19): a Multicenter Cohort Study.

BACKGROUND: This study aimed to investigate the cardiac manifestations of coronavirus disease 2019 (COVID-19). METHODS: From February to March 2020, we prospectively and retrospectively enrolled consecutive patients diagnosed with COVID-19. Patient's data such as the demographic characteristics, symptoms, vital signs, laboratory and radiologic findings, electrocardiographic, and echocardiographic data, including the global longitudinal strain (GLS) of both ventricles, were obtained. RESULTS: Forty patients (median age, 58 years; 50% men) were enrolled in the initial analysis. Patients were classified into severe and nonsevere groups based on the current guidelines. The 13 patients in the severe group were significantly older, had a greater prevalence of bilateral pneumonia and leukocytosis, and higher aspartate transaminase levels than patients in the nonsevere group. Patients in the severe group had a slightly lower left ventricular ejection fraction (LVEF) than those in the nonsevere group (median [interquartile range], 61.0% [58.5%, 62.3%] vs. 66.7% [60.6%, 69.8%], P = 0.015). In a subgroup of 34 patients in whom GLS could be analyzed, patients in the severe group had a significantly impaired left ventricular GLS (LVGLS) than those in the nonsevere group (-18.1% [-18.8%, -17.1%] vs. -21.7% [-22.9%, -19.9%], P = 0.001). There were no significant differences in total wall (RVGLStotal, -19.3% [-23.9%, -18.4%] vs. -24.3% [-26.0%, -22.6%], P = 0.060) and free wall (RVGLSfw, -22.7% [-27.2%, -18.6%] vs. -28.8% [-30.4%, -24.1%], P = 0.066) right ventricle GLS (RVGLS). CONCLUSION: Patients with severe COVID-19 had lower LVEF and LVGLS. RVGLS was not different between patients with severe and nonsevere COVID-19.

The Implication of Cardiac Injury Score on In-hospital Mortality of Coronavirus Disease 2019.

BACKGROUNDS: The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has spread worldwide. Cardiac injury after SARS-CoV-2 infection is a major concern. The present study investigated impact of the biomarkers indicating cardiac injury in coronavirus disease 2019 (COVID-19) on patients' outcomes. METHODS: This study enrolled patients who were confirmed to have COVID-19 and admitted at a tertiary university referral hospital between February 19, 2020 and March 15, 2020. Cardiac injury was defined as an abnormality in one of the following result markers: 1) myocardial damage marker (creatine kinase-MB or troponin-I), 2) heart failure marker (N-terminal-pro B-type natriuretic peptide), and 3) electrical abnormality marker (electrocardiography). The relationship between each cardiac injury marker and mortality was evaluated. Survival analysis of mortality according to the scoring by numbers of cardiac injury markers was also performed. RESULTS: A total of 38 patients with COVID-19 were enrolled. Twenty-two patients (57.9%) had at least one of cardiac injury markers. The patients with cardiac injuries were older (69.6 ± 14.9 vs. 58.6 ± 13.9 years old, P = 0.026), and were more male (59.1% vs. 18.8%, P = 0.013). They showed lower initial oxygen saturation (92.8 vs. 97.1%, P = 0.002) and a trend toward higher mortality (27.3 vs. 6.3%, P = 0.099). The increased number of cardiac injury markers was significantly related to a higher incidence of in-hospital mortality which was also evidenced by Kaplan-Meier survival analysis (P = 0.008). CONCLUSION: The increased number of cardiac injury markers is related to in-hospital mortality in patients with COVID-19.

Clinical significance of early-diastolic tissue velocity imaging of lateral mitral annulus for prognosis of nonischemic left ventricular dysfunction.

PURPOSE: We explored the potential of tissue velocity imaging (TVI) for prognosis of nonischemic left ventricular (LV) dysfunction (LVD). METHODS: We reviewed 138 nonischemic LVD patients (58 ± 14 years) who underwent both cardiac magnetic resonance (CMR) and echocardiography. Septal and lateral mitral annular TVI data were compared with late gadolinium enhancement (LGE) on CMR. During a mean follow-up of 24 months, recovery (>15%) of LV ejection fraction and clinical outcomes (cardiovascular death and heart failure hospitalization) were assessed. RESULTS: LGE was commonly observed in the basal anteroseptal, inferoseptal, and inferior segments, but infrequently observed in the anterolateral segment. LGE was associated with lower early diastolic, septal (Sep-e' = 5.2 ± 2.0 vs 6.9 ± 2.0 cm/s, P = .031) and lateral (Lat-e' = 7.3 ± 3.0 vs 9.5 ± 2.0 cm/s, P < .001) TVI. The relationship between Lat-e' and anterolateral LGE (area under the curve, AUC 0.834) was much better than that between Sep-e' and inferoseptal LGE (AUC 0.699). The 60 patients with LVD reversibility revealed higher Lat-e' (9.8 ± 2.0 vs 6.7 ± 2.2 cm/s, P < .001) and lower LGE burden (7.3 ± 9.0 vs 22 ± 10%, P < .001), while Lat-e' ≤ 7.8 cm/s appeared unfavorable for 31 events patients. On multivariate analyses, Lat-e' (HR 0.79, 95% CI 0.63-0.99, P = .044) and LVD reversibility (HR 0.53, 95% CI 0.16-0.90, P = .018) were still meaningful together with LGE segments and burden. CONCLUSION: Lat-e' was related with LVD reversibility and a significant predictor of clinical outcomes.

Intraventricular Flow: More than Pretty Pictures.

Patients with heart failure show myocardial, valvular, and electrical dysfunction, which results in enlarged cardiac chambers and increased intracardiac volume and pressure. Intracardiac flow analysis can provide information regarding the shape and wall properties, chamber dimensions, and flow efficiency throughout the cardiac cycle. There is increasing interest in vortex flow analysis for patients with heart failure to overcome limitations of conventional parameters. In conjunction with the conventional structural and functional parameters, vortex flow analysis-guided treatment in heart failure might be a novel option for cardiac physicians.

Implication of ultrasound contrast-enhancement of carotid plaques in prevalence of acute coronary syndrome and occurrence of cardiovascular outcomes.

PURPOSE: Ultrasonographic contrast enhancement of carotid plaque (CECP) has been used to detect neovascularization of vasa vasorum and plaque. However, it is uncertain whether CECP can provide risk stratification of coronary artery disease (CAD). This study aimed to evaluate the relationship between CECP and manifestations of acute coronary syndrome (ACS) in established CAD patients and to explore the prognostic implication of CECP for cardiovascular (CV) clinical outcomes. METHODS: A medical record review revealed that contrast-enhanced ultrasonography was performed to evaluate carotid atherosclerosis in 209 coronary artery-stented and 105 non-stented patients. The rate of ACS manifestations was compared depending on contrast uptake patterns: grade 0, absent; grade 1, dot; and grade 2, diffuse pattern. CV primary outcomes were assessed during a mean 7.6 months of follow-up. RESULTS: Male sex, smoking, history of old myocardial infarction, intensive medications, and a favorable lipid profile were common in the stented versus non-stented group. Patients with grade 2 CECP had a higher rate of ACS, greater plaque thickness, and class I-II of Gray-Weale plaque echogenicity. During follow-up, 10 coronary revascularizations (nine ACSs), six strokes, and four heart failures occurred. Grade 2 CECP was more closely related with CV primary outcomes and showed a tendency toward more acute CV outcomes. CONCLUSION: ACS manifestations were proportionate to CECP grade. Diffuse CECP uptake could be a risk factor for acute CV outcomes.

Usefulness of Frequency Domain Optical Coherence Tomography Compared with Intravascular Ultrasound as a Guidance for Percutaneous Coronary Intervention.

OBJECTIVES: To compare outcomes and rates of optimal stent placement between optical coherence tomography (OCT) and intravascular ultrasound (IVUS) guided percutaneous coronary intervention (PCI). BACKGROUND: Unlike IVUS-guided PCI, rates of clinical outcomes and optimal stent placement have not been well characterized for OCT-guided PCI. METHODS: The study enrolled 290 patients who underwent implantation of a second generation drug eluting stent under OCT (122 patients) or IVUS (168 patients) guidance. The two groups were compared after adjusting for baseline differences using 1:1 propensity score matching (PSM) (114 patients in each group). Optimal stent placement was defined as achieving an adequate lumen (optimal minimum stent area [MSA > 4.85 mm(2) for OCT, >5 mm(2) for IVUS] or a final MSA ≥ 90% of the distal reference lumen area, without edge dissection, incomplete stent apposition, or tissue prolapse), or otherwise performing additional interventions to address suboptimal post-stenting OCT or IVUS findings. The primary endpoint was one-year cumulative incidence of major adverse cardiac events (MACE; cardiac death, myocardial infarction and target lesion revascularization). Definite or probable stent thrombosis (ST) rates were evaluated. RESULTS: In adjusted comparisons between OCT and IVUS groups, there was no significant difference in rates of MACE (3.5% vs. 3.5%, P = 1.000) and ST (0% vs. 0.9%, P = 1.000) at 1 year, optimal stent placement (89.5% vs. 92.1%, P = 0.492), and further intervention (7.9% vs.13.2%, P = 0.234), despite OCT significantly more frequently detecting tissue prolapse (97.4% vs. 47.4%, P < 0.001), and numerically more edge dissection (10.5% vs. 4.4%, P = 0.078) or incomplete stent apposition (48.2% vs. 36.8%, P = 0.082). CONCLUSIONS: OCT guidance showed comparable results to IVUS in mid-term clinical outcomes, suggesting that OCT can be an alternative tool for stent placement optimization.

Left ventricular twist and ventricular-arterial coupling in hypertensive patients.

BACKGROUND: Left ventricular (LV) twist is usually influenced by LV hypertrophy resulting from hypertension or vascular stiffness. Vascular stiffness would increase arterial elastance (Ea), whereas LV end-systolic stiffness (Ees) could be influenced by LV hypertrophy. Therefore, in hypertensive patients, we assessed the extent to which ventricular-arterial coupling (VAC; Ea/Ees) affects LV twist, which may be a compensatory mechanism for systolic dysfunction. METHODS: Hypertensive patients (n = 128) and healthy controls (n = 40) underwent conventional and speckle tracking echocardiography including LV twist. Ea and Ees were estimated noninvasively by echocardiography. Patients were divided into 3 tertiles according to the twist angle. Univariate and multivariate regression analyses were performed to test the influence of VAC on twist. RESULTS: Patients in the lowest LV twist tertile had larger LV end-systolic volume, lower ejection fraction, lesser mid-wall fractional shortening (MWFS), and higher LV mass index (LVMI), compared to those with the highest tertile. They showed the lower septal tissue Doppler velocity, and global longitudinal and circumferential strain. With regard to VAC, Ea was similar among 3 groups, but Ees was significantly decreased in patient with lower tertile, resulting in increased VAC (1.1 ± 0.2 vs. 0.9 ± 0.1 vs. 0.7 ± 0.1, P < 0.001). While LV twist showed significant correlations with Ees, MWFS, and LVMI, VAC (ß = -14.92, P < 0.001) was most associated with twist in a multivariate analysis. CONCLUSIONS: LV twist was significantly associated with VAC in accordance with LV function; LV twist and VAC decreased progressively as LV systolic function deteriorated, while being enhanced during the well-compensated phase.

Proteome-wide Characterization and Pathophysiology Correlation in Non-ischemic Cardiomyopathies.

BACKGROUND AND OBJECTIVES: Although the clinical consequences of advanced heart failure (HF) may be similar across different etiologies of cardiomyopathies, their proteomic expression may show substantial differences in relation to underlying pathophysiology. We aimed to identify myocardial tissue-based proteomic characteristics and the underlying molecular pathophysiology in non-ischemic cardiomyopathy with different etiologies. METHODS: Comparative extensive proteomic analysis of the myocardium was performed in nine patients with biopsy-proven non-ischemic cardiomyopathies (3 dilated cardiomyopathy [DCM], 2 hypertrophic cardiomyopathy [HCM], and 4 myocarditis) as well as five controls using tandem mass tags combined with liquid chromatography-mass spectrometry. Differential protein expression analysis, Gene Ontology (GO) analysis, and Ingenuity Pathway Analysis (IPA) were performed to identify proteomic differences and molecular mechanisms in each cardiomyopathy type compared to the control. Proteomic characteristics were further evaluated in accordance with clinical and pathological findings. RESULTS: The principal component analysis score plot showed that the controls, DCM, and HCM clustered well. However, myocarditis samples exhibited scattered distribution. IPA revealed the downregulation of oxidative phosphorylation and upregulation of the sirtuin signaling pathway in both DCM and HCM. Various inflammatory pathways were upregulated in myocarditis with the downregulation of Rho GDP dissociation inhibitors. The molecular pathophysiology identified by extensive proteomic analysis represented the clinical and pathological properties of each cardiomyopathy with abundant proteomes. CONCLUSIONS: Different etiologies of non-ischemic cardiomyopathies in advanced HF exhibit distinct proteomic expression despite shared pathologic findings. The benefit of tailored management strategies considering the different proteomic expressions in non-ischemic advanced HF requires further investigation.

Temporal Trends, Risk Factors, and Clinical Outcomes of De Novo Lymphoproliferative Disorders After Heart Transplantation.

BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) is an important cause of morbidity and mortality in heart transplant (HTx) recipients. However, previous studies of PTLD after HTx are limited to single-center analyses or extrapolated from all solid organ transplantations. OBJECTIVES: The authors analyzed the temporal trends, risk factors, and clinical outcome of de novo PTLD specifically after HTx. METHODS: Using multi-institutional, multinational data from the International Society for Heart and Lung Transplantation Thoracic Organ Transplant Registry, the authors evaluated the real-world data of PTLD after HTx, transplanted between January 2000 and June 2015. Multivariable analysis was done to identify risk factors for PTLD development after HTx. RESULTS: Among 28,136 HTx recipients, 1,069 (3.8%) developed PTLD within 10 years of transplantation. PTLD showed a bimodal age pattern with peak incidence in patients of pediatric age and late adulthood at transplantation. The early transplant era (2000-2007 vs 2008-2015), male recipient, and EBV donor-positive-recipient-negative match were independent risk factors of PTLD development within 3 years of transplantation, whereas maintenance therapy with cyclosporine vs tacrolimus at initial discharge was associated with a lower incidence. PTLD development within 3 years of transplantation was significantly associated with mortality (HR: 2.42 [95% CI: 2.01-2.91]; P < 0.001). Survival after PTLD diagnosis was higher in the recent transplant era. CONCLUSIONS: PTLD is relatively rare, but potentially fatal, post-transplant malignancy. PTLD incidence and mortality after HTx have decreased in the recent era. Strategies to minimize the risk of PTLD, and ensure early diagnosis and effective treatment are likely to improve outcomes in HTx.